PMID- 2243827 TI - Teaching the Heimlich maneuver. PMID- 2243828 TI - Skiing and snowboarding injuries. When schussing is a pain. AB - Downhill and cross-country skiing and snowboarding are growing rapidly in popularity. With the ever-increasing number of participants, physicians must be prepared to deal with the injuries specific to these sports. More important, physicians need to use epidemiologic data to advise patients of methods to minimize the risk of injury as they participate in these healthy and vigorous winter sports. PMID- 2243829 TI - Hypothermia. Safe and efficient methods of rewarming the patient. AB - Hypothermia, a relatively common problem in the winter months, can cause significant morbidity. It presents in a variety of situations and affects a wide age range. Diagnosis requires a high index of suspicion, because the symptoms, which are primarily related to the central nervous system, are not distinctive. Appropriate management requires accurate measurement of core body temperature. Treatment is centered on rewarming the patient safely and efficiently while providing other supportive measures. Care should be taken to avoid arrhythmias. Simple precautions greatly reduce the risk of hypothermia. PMID- 2243830 TI - Frostbite. Methods to minimize tissue loss. AB - If frostbite is to be treated successfully, direct and indirect effects of injury must be understood. Rapid rewarming helps to preserve tissue by limiting the amount of direct cellular injury. Selective management of blisters helps protect the subdermal plexus, and application of Aloe vera cream (eg, Dermaide Aloe Cream) combats the local vasoconstrictive effects of thromboxane. Oral administration of ibuprofen decreases systemic levels of thromboxane. PMID- 2243831 TI - Treating systemic fungal infections in AIDS patients. Prolonging life against the odds. AB - Fungal infections have become one of the major causes of death among immunocompromised patients, particularly patients with AIDS. Accurate and quick diagnosis is difficult; therefore, empirical therapy is often necessary. This scenario is complicated by the fact that most antifungal agents are toxic at the doses used or relatively ineffective against deep-seated mycoses. Because the population of AIDS patients is increasing, physicians will be faced more often with the management of systemic fungal infections. Despite the current bleak prognosis for these patients, several new antigen detection tests are being developed and triazole agents are proving to be effective and less toxic than their predecessors. Many cases of systemic mycoses do result in mortality, but appropriate treatment can both prolong life and improve its quality. PMID- 2243832 TI - Evaluation of atracurium in myasthenic patients undergoing thymectomy. AB - Myasthenia gravis is an autoimmune disease involving the acetylcholine receptors at neuromuscular junctions. Perioperative management of patients with myasthenia gravis is complicated by their enhanced sensitivity to nondepolarizing neuromuscular blocking agents and their resistance to depolarizing drugs (1). Prolonged respiratory depression commonly occurs when these agents are used. Atracurium dibesilate is one of a new series of nondepolarizing agents and is promising by virtue of its rapid degradation by 'Hoffmann elimination', leaving products with little or no muscle blocking activity. After encouraging results were obtained with atracurium (2-6), we investigated the neuromuscular blocking effect of different doses of the drug (0.2 mg/kg, 0.5 mg/kg) in sixteen myasthenic patients undergoing thymectomy, with continuous monitoring of neuromuscular function. PMID- 2243833 TI - On the application of least-squares refinement to complex structures--resolving enantiomorphous phase ambiguity. AB - A least-squares refinement procedure has been proposed for resolving enantiomorphous ambiguity of noncentrosymmetric structures containing heavy atoms in a centrosymmetric arrangement. During the least-squares refinement of a pseudo centrosymmetric image containing both enantiomorphs, the temperature factors of atoms in one enantiomorph shift in the same direction, while those of the other shift in the opposite direction. Accordingly the true structure can be distinguished easily from its enantiomorph. Tests on four unknown structures have shown that the method is very powerful. PMID- 2243834 TI - Generation and partial characterization of monoclonal antibodies against solubilized membrane fraction of human spermatozoa. AB - Human sperm membrane antigens extracted by deoxycholate (DOC) were used to immunize BALB/c mice. Hybrid cell lines secreting sperm-specific monoclonal antibodies were generated by cell fusion in a semi-solid medium and screened by indirect immunofluorscent assay using live and methanol-fixed sperm. Out of 850 hybrid clones from cell fusion, 28 were shown to secrete sperm-specific antibodies which reacted with the acrosome, equatorial segment, whole surface plasma membrane or tail of spermatozoa. Finally, seven hybrid cell lines were established and shown to secrete monoclonal antibodies which had no cross reactivity with any human tissues other than testis and sperm. The majority were also shown to inhibit fertilization of mouse oocytes in vitro and human sperm penetration of zone-free hamster ova. Western blot analysis revealed that some of these antibodies reacted with sperm membrane antigens of distinct molecular size. PMID- 2243835 TI - Establishment of a human B cell line that responds specifically to B cell growth factor. AB - A human B cell line (3D5) that responds specifically to B cell growth factor (BCGF) has been developed by a sequence of Staphylococcus aureus Cowen I activation, EB virus immortalization, and cloning. Proliferative response to PHA stimulated T cell supernatant (PHA-T-Sup) and nonresponsiveness to rIL-2 stimulation were factors used to screen positive cells. Phenotype analysis with a flow cytometer indicated that: 1) 3D5 is a B cell line: 100% of the cells were positive for B1 marker and 59% were positive for sIg, while T3 and Mo 1 were negative; 2) 3D5 is an activated B cell line: both Tac and 4F2 markers of activated (but not of resting) B cells were 100% positive; 3) 3D5 expresses high molecular weight BCGF (HMW-BCGF) receptor-associated epitope BA5. 3D5 cells proliferated in response to cpBCGF stimulation in a dose-dependent manner. HMW BCGF also induced 3D5 cells to proliferate. Interestingly, no proliferation could be detected in the presence of rIL-2, rIL-4, or rIFN-r. The data show that 3D5 cells are specifically BCGF-responsive B cells. Using 3D5 cells as target, BCGF activity was detected in crude BCGF preparation sedimented by 85% (NH4)2SO4 and chromatographed in a DEAE-Sephadex A-25 column from PHA-T-Sup. T24 cell supernatant with B cell differentiation factor (BCDF) activity could not induce 3D5 cells to differentiate into immunoglobulin-secreting cells. PMID- 2243836 TI - Imaging techniques for the diagnosis of renal tumors. AB - In recent years, diagnostic imaging techniques, especially ultrasonography (US) and CT scanning, have been widely adopted in clinical practice, making early accurate diagnosis of renal tumors possible. A total of 452 cases of renal tumors have been admitted to the institute since 1951, of which 220 were seen from 1951 to 1979 and 232 in the past 9 years (1980-1988). The frequency of renal parenchymal tumors was obviously higher in the latter group, including asymptomatic renal carcinoma in 20.2% and hamartoma in 38.1%. All these were discovered on routine physical check-up by ultrasonography and/or CT scanning and would otherwise have gone undiagnosed on conventional urography. Ultrasonography and CT can also reveal the nature and the extent of the tumor. The idea that "a renal tumor should be considered malignant unless pathologically proven otherwise" is no longer valid. However, general manifestations of renal carcinoma, such as elevated erythrocyte sedimentation rate (ESR), hypertension, malaise, anemia, fever and hypercalcemia, still deserve proper attention. We suggest that ultrasonography of both kidneys should be mandatory in routine physical check-up, as far as the urinary system is concerned, in order to discover asymptomatic renal tumors. PMID- 2243837 TI - Early and late results of total gastrectomy in treatment of advanced adenocarcinoma of the cardia. AB - Sixty-six patients with advanced adenocarcinoma of the cardia underwent total gastrectomy between 1978 and 1986. The operative morbidity rate was 7.5% and the hospital mortality rate (1 month) was 1.5%. The postoperative 1, 3, 4, and 5 year survival rates were 69%, 30.7%, 20% and 13.8% respectively. The quality of life after surgery was improved. Pathological type, lymph node metastasis, completeness of resection and postoperative chemotherapy were the main factors influencing postoperative survival time. Indications for total gastrectomy and the advantages of transthoracic total gastrectomy are discussed. PMID- 2243838 TI - Diagnosis and treatment of idiopathic necrosis of the femoral head. AB - Fifteen cases, 27 hips, of idiopathic necrosis of the femoral head (INFH) were included in our series. The roles of radiography, isotopic bone scanning, intraosseous pressure measurement and intraosseous venography in the diagnosis of INFH were evaluated. Radiological examination could not reveal early cases, while isotopic bone scanning was more sensitive. There was an increase of intraosseous pressure in most of the diseased hips, and intraosseous venography showed abnormalities in all examined hips. The latter two tests could therefore detect early INFH. Core decompression was performed in 23 hips, 21 of which were followed for 7 to 27 months. Functional evaluation was good or excellent in 18 hips. Radiological re-examination remained unchanged in 19 hips. Postoperative intraosseous pressure measurement and intraosseous venography revealed a decrease of intraosseous pressure and improvement of venous drainage. Core decompression is therefore an ideal method of treatment for early INFH. PMID- 2243839 TI - S100 protein-positive dendritic cells and the significance of their density in gastric precancerous lesions. AB - Quantitative analysis of dendritic cells (DC's) was carried out in tissue specimens of normal gastric mucosa (n = 15), gastric ulcer (n = 19), chronic atrophic gastritis (n = 28), and gastric carcinoma (n = 65) by ABC immunostaining with S100 protein antibody. Significant increases in DC number were observed in chronic atrophic gastritis with type III intestinal metaplasia and/or grade II, III dysplasia. The result suggests that DC's are potentially capable of presenting neoantigens associated with malignant transformation at the precancerous stage when malignant morphological changes have not yet taken place. Combined with routine diagnostic methods, the serial monitoring of DC density in gastric mucosa may be useful in the follow-up of premalignant lesions in the stomach and the diagnosis of early gastric carcinoma. PMID- 2243840 TI - Proceedings of the National Academy of Sciences of the United States of America. Annual subject and author indexes. PMID- 2243841 TI - Implementation of three-dimensional image reconstruction for multi-ring positron tomographs. AB - In view of the number of PET studies involving low count rate acquisitions, there has been increasing interest recently in the development of positron cameras capable of fully three-dimensional acquisition and reconstruction. This interest has given impetus to the study of algorithms for 3D reconstruction, including those algorithms suitable for application to multi-ring PET scanners. While 2D reconstruction methods can often be generalised to 3D, a number of implementation problems arise which are unique to the 3D approach. This paper examines some of the difficulties associated with the generalisation of the filtered backprojection algorithm to 3D, paying particular attention to the approximations and variable transformations required for application to data from a multi-ring scanner. PMID- 2243842 TI - Characterising the microstructure of random media using ultrasound. AB - This paper describes a technique of forming images of the average size and scattering strength of scatterers in a random medium using ultrasound. Quantitative ultrasound images provide a more direct interpretation of the underlying structure of the medium, e.g. size, shape, number and elastic properties of scatterers, and increased detectability for regions of varying structure. A signal-to-noise analysis was used to show quantitatively how properties of the imaging system influence low-contrast detectability in quantitative ultrasound images. In one experiment, signal-to-noise measurements using phantoms were compared with B-mode imaging for several transducer bandwidths to observe variations in image contrast and speckle noise. The findings are being used to optimise the design of quantitative imaging systems for specific diagnostic tasks. PMID- 2243843 TI - Ultrasonic attenuation and velocity in bone. AB - The measurement of attenuation and velocity of ultrasound in cancellous bovine femora has been studied. The dependence of both attenuation between 0.2 and 0.8 MHZ and velocity on the bone density has been measured. The results show a correlation coefficient of around 0.5 for attenuation and density, and a value of roughly 0.85 for velocity and density. The clinical consequences for the use of low frequency ultrasound as a diagnostic tool in bone disease are discussed. PMID- 2243844 TI - An improved in vivo neutron activation system for measuring kidney cadmium. AB - An in vivo neutron activation system for measuring kidney cadmium has been redesigned, firstly to reduce ambient dose levels and, secondly, to improve the cadmium signal to neutron dose ratio by modifying the neutron spectrum from 238Pu/Be, by interposing a beryllium premoderator. The ambient dose was reduced by a factor of seven. The overall system performance (lower limit of detection for a given dose) was improved by 40-50%. This 238Pu/Be based system now performs as well as or better than analogous 252Cf systems, without the drawback of the relatively short half life of 252Cf. PMID- 2243845 TI - Methods of image reconstruction from projections applied to conformation radiotherapy. AB - The problem of optimizing the dose distribution for conformation radiotherapy with intensity modulated external beams is similar to the problem of reconstructing a 3D image from its 2D projections. In this paper we analyse the relationship between these problems. We show that the main image reconstruction methods, namely filtered backprojection and iterative reconstruction, can be directly applied to conformation therapy. We examine the features of each of these methods with regard to this new application and we present first theoretical results. PMID- 2243846 TI - A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury. AB - We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury. The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection. Graft loss of 10 percent or more occurred in 17 patients (33 percent)- due to infection in 16. Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5). The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group. Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment. Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group. No graft infections were caused by resistant organisms or yeast in the silver nitrate group. This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not. PMID- 2243847 TI - Conservative treatment of cutis aplasia. AB - Three cases of cutis aplasia are presented. The defects involved include full thickness defects of scalp and cranium as well as full-thickness skin defects of the abdomen and thigh. All patients were treated conservatively with the use of Silvadene cream dressings. Healing was obtained in all patients. PMID- 2243848 TI - Calvarial sutural abnormalities: metopic synostosis and coronal deformation--an anatomic, three-dimensional radiographic, and pathologic study. AB - The purposes of this study were (1) to evaluate the histologic differences between synostotic versus deformational suture abnormalities and (2) to correlate these histologic findings with anatomic and three-dimensional computed tomographic (CT) scans. We examined three infants with premature metopic synostosis; one infant also had microcephaly trisomy 13 and curious overriding of the coronal sutures. The three-dimensional CT scans demonstrated obliteration of the metopic suture inferiorly. Histologic sections of this suture showed complete bony stenosis. The same pattern was found in all three infants, including the two infants with trigonocephaly who did not have trisomy 13 or microcephaly. In the trisomy 13 infant, the overlapped inferior coronal suture was obliterated on CT examination. However, histologic sections in this region showed a merging of bone; there was no synostosis. In summary, three-dimensional CT re-formation correlated with metopic suture histology. "Stenotic" fusion existed in all infants with trigonocephaly, those with normal and abnormal karyotypes, with and without microcephaly. However, three-dimensional CT re-formation of the trisomic infant showed opacification of the coronal suture in the areas of greatest overlap, whereas histology revealed a curious bone remodeling pattern, possibly a precursor to "deformational" craniosynostosis. PMID- 2243849 TI - The effect of early fronto-orbital advancement on frontal sinus development and forehead aesthetics. AB - The frontal sinuses make an important contribution to normal forehead and glabellar contour. This study was designed to test our clinical impression that early fronto-orbital ("frontal bone") advancement could have an adverse effect on frontal sinus development and consequently on forehead aesthetics. A retrospective study was conducted on 11 patients who had undergone fronto-orbital advancement and also had a long period of follow-up at the Institute of Reconstructive Plastic Surgery at New York University. The longitudinal cephalometric data were compared with unoperated controls. With one exception, no patient who underwent bilateral fronto-orbital advancement developed a frontal sinus, and all such patients had a flattened brow contour when compared with unoperated patients, of whom 82 percent developed at least one frontal sinus. Of the three patients who underwent unilateral fronto-orbital advancement for plagiocephaly (flattened forehead), two developed a frontal sinus but only on the unoperated side and one developed bilateral frontal sinuses. The two patients with unilateral frontal sinus development had a particularly obvious deformity resulting from normal glabellar projection on the unoperated side and a flattened contour on the operated side. Fronto-orbital advancement affects forehead aesthetics and should be performed only in infant patients with moderate to severe deformities. patients with plagiocephaly whose deformity is sufficiently severe to warrant surgery should preferably undergo bilateral fronto-orbital advancement (by the technique described) rather than unilateral advancement in order to avoid the brow asymmetry that results from unilateral frontal sinus development. PMID- 2243850 TI - Evaluation of HTR polymer as a craniomaxillofacial graft material. AB - An experimental animal study was undertaken to evaluate the potential use of HTR polymer as a craniomaxillofacial reconstructive material. Its properties of marked hydrophilicity, a negative surface charge, and extensive porosity combined with a calcium graft coating suggested favorable osteoconductive properties. Four sites of the rabbit craniomaxillofacial skeleton were evaluated by placement of both inlay and onlay implants. Postoperative assessment at 60, 120, and 240 days consisted of histologic evaluation by tetrachrome staining of calcified sections. At 60 days, extensive osseous ingrowth into the inlay implants had occurred extending up to 2000 microns. The onlay implants, however, exhibited more limited ingrowth extending only 100 to 200 microns into the material. Over the ensuing 120- and 240-day postoperative periods, the average depth of bony ingrowth did not progress in either the inlay or onlay specimens over that observed at 60 days. Differences also were noted between the inlayed skeletal sites, with increased marrow at the recipient site resulting in increased bony ingrowth. The material appears to be biocompatible, with no evidence of infection, inflammatory reaction, or bone resorption observed around any of the implants. The implants exhibited a significant osteoconductive capability that was most manifest when implants were exposed to bleeding cortical/marrow surfaces as inlay grafts. PMID- 2243851 TI - Does interference with mucoperiosteum and palatal bone affect craniofacial growth? An experimental study in beagles. AB - This study was designed to assess the effects of raising mucoperiosteal flaps and exposing palatal bone at the time of palatoplasty. Using 62 beagle puppies as subjects, we tested the hypothesis that raising mucoperiosteal flaps does not interfere with craniofacial growth. We further hypothesized that the size of the area of bone exposed following palatoplasty does affect subsequent craniofacial growth. The animals were divided into four groups: two control groups (unoperated and unrepaired) and two experimental groups. In the first experimental group, two flap palatoplasty was used to close the surgically induced palatal defect, leaving narrow strips (0 to 2.5 mm) of bone exposed lateral to the flaps. In the second group, one flap was raised to close the defect, leaving a wide area (5 to 6 mm) of palatal bone exposed on one side. Thirty-four direct craniometric measurements were analyzed. Animals that had elevation of both mucoperiosteal flaps with narrow strips of denuded bone on both sides had less severe craniofacial growth aberrations than those in which the defect was left unrepaired or was repaired with one mucoperiosteal flap leaving a wider area of bare bone exposed. These findings suggest that raising mucoperiosteal flaps is less detrimental to craniofacial growth than leaving large areas of exposed palatal bone. PMID- 2243852 TI - Rigid fixation of internal orbital fractures. AB - When large portions of the internal orbit are destroyed (two to four walls), standard bone-grafting techniques for immediate and late orbital reconstruction may not yield predictable eye position. Critical bone support is most often deficient inferomedially. CT analysis of orbital volume in cases where eye position was unsatisfactory reveals that displacement of bone grafts is one mechanism of the unsatisfactory result. Other mechanisms include undercorrection and bone-graft resorption. In order to minimize postoperative bone-graft displacement, titanium implants were used to span large defects in the internal orbit to provide a platform for bone-graft support. Twenty-six implants were placed in immediate and 12 were placed in late orbital reconstructions. More reliable bone-graft position resulted. Two late infections have occurred resulting in implant removal in a 3-year period. PMID- 2243853 TI - 585 nm for the treatment of port-wine stains. AB - Although the flashlamp-pulsed-dye laser has been successfully used for the treatment of port-wine stains (PWS) at 577 nm, a number of adult patients had incomplete clearance of their birthmarks with this treatment modality because of residual vessels lying beyond the 0.75-mm penetration depth of 577-nm irradiation. Fifteen adult patients, of whom nine were previously treated with limited success at 577 nm (group A), and six untreated patients (group B) were included in the study. For the group A patients, treatment with 585 nm produced successful clearance of the birthmark. For the six patients in group B, parallel treatment of different sites of the same lesion coupled with skin biopsies and histologic examination revealed that a change in the wavelength from 577 to 585 nm allowed the laser light to penetrate from the midreticular dermis into the subcutaneous fat. This explained the clearance achieved at 585 nm and not at 577 nm. PMID- 2243854 TI - Reasons why mastectomy patients do not have breast reconstruction. AB - Breast reconstruction after mastectomy is valuable, yet only a small percentage of eligible patients ever have reconstruction. Little has been done to determine why so few patients proceed with reconstructive surgery. A homogeneous population of mastectomy patients, some of whom underwent breast reconstruction while others did not, were surveyed regarding their attitudes about breast reconstruction. A total of 245 women were surveyed. One-hundred and fifty-eight (64 percent) responded, 71 of whom had been reconstructed while 87 had not. Comparison of the responses of the two groups suggests factors that play a role in determining whether the mastectomy patient will accept or decline the option of breast reconstruction. Considerations that made it less likely that a woman would pursue reconstruction included advanced age at the time of mastectomy, concern about complications from further surgery, uncertainty about outcome, and fear about the effect of reconstruction on future problems with breast cancer. Marital status, receiving chemotherapy, or knowing a patient who had a bad result from reconstruction did not affect the decision. An awareness and understanding of these factors may be helpful to physicians in counseling patients and in increasing the number of women who enjoy the benefits of breast reconstruction. PMID- 2243855 TI - Mammographic measurements before and after augmentation mammaplasty. AB - Thirty-five augmented women underwent mammography using both the standard implant compression technique and, when possible, the implant-displacement technique; all had preaugmentation film-screen mammography available for evaluation. The area of mammographically visualized breast tissue before and after augmentation mammaplasty was measured using a transparent grid. Patients with subglandular implants had a mean decrease of 49 percent of measurable tissue area with compression mammography and a 39 percent decrease with displacement mammography. Patients with submuscular implants had a 28 percent decrease in measurable tissue area with compression mammography and a 9 percent decrease with displacement mammography. Anterior breast tissue was seen better with displacement mammography; posterior breast tissue, with compression mammography. Most patients had some degree of parenchymal scarring and lower image quality after augmentation. State-of-the-art mammography was not possible in most patients augmented with silicone-gel-filled implants. PMID- 2243856 TI - Assessment of the lymphocyte response to silicone. AB - The biocompatibility of silicone is once again the focus of increased interest. Long considered inert, silicone has now been reported to be responsible for macrophage inhibition in rats and to possibly cause adjuvant disease in humans, and the related compound silica has elicited an antibody response in mice. The present study evaluates lymphocytic response to silicone as expressed by the demonstration of immunologic memory, or changes in specific lymphocyte subpopulations. Thirty-six female Lewis rats (250 gm body weight) were used as test animals. Group 1 (n = 12) was injected subcutaneously with 2.5 ml Freund's Complete Adjuvant (FCA) alone. Group 2 (n = 12) was injected with 2.5 ml FCA sonicated with silicone gel. Group 3 (n = 6) was injected with 2.5 ml FCA, and at 4 weeks, gel-filled silicone implants were placed subcutaneously. Group 4 (n = 6) was injected with 2.5 ml FCA sonicated with silicone gel, and gel-filled silicone implants were placed at 4 weeks. An additional group of six rats (group 5) served as control for the experimental animals, and a group of four rats (group 6) served as naive control. Groups 1 and 2 were sacrificed at 4 weeks, and splenic lymphocytes were obtained for lymphocyte transformation assays performed against silicone. Assays also were run with the addition of the known mitogens Con A, PHA, LPS, and pokeweed. Cytofluorographic analysis of pan-T, T-helper, T suppressor, and B-cell populations was performed. Groups 3, 4, 5, and 6 were harvested at 8 months, and splenic lymphocytes were subjected to lymphocyte transformation assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243857 TI - The lateral arm fascial free flap: its anatomy and use in reconstruction. AB - Free fascial transfer has been used for reconstruction of gliding surfaces of the upper and lower extremities or when thin, pliable coverage is required (hand, heel, nose, and ear). In our experience with the lateral arm fasciocutaneous flap, we have found that the fascia alone is an excellent source of tissue for free flap transfer. A thorough investigation of the microscopic, gross, and radiographic anatomy of the lateral arm fascia was undertaken by the study of 25 fresh cadavers. Vascular pathways were mapped, their locations were analyzed, and then they were correlated with the elevation, design, and transfer of the flap. The lateral arm has a large fascial component located anterior and posterior to the lateral intermuscular septum, which itself lies between the triceps and the brachialis and brachioradialis muscles. It is perfused by the posterior radial collateral artery (PRCA), one of the terminal branches of the profunda brachii. This vessel (PRCA) provides at least four fascial branches from 1 to 15 cm proximal to the lateral epicondyle, the largest of which is located an average of 9.7 cm superior to the lateral epicondyle. Fascia up to 12 x 9 cm may be used with good axial perfusion. The histologic cross sections demonstrate the complex anatomy of the fascia itself, as well as its relation to the nutrient vessels. We have applied the lateral arm fascial flap in five cases of upper extremity reconstruction. We have also found this flap valuable in preservation of underlying anatomic detail for total reconstruction of the ear and nose when local tissue and more conventional flaps were not available. PMID- 2243858 TI - The efficacy of methylprednisolone in reducing flap edema. AB - It has been suggested that systemic steroids reduce postoperative flap edema. This has been poorly documented by several reports based on subjective clinical observations. In an effort to provide quantitative data on methylprednisolone and edema, a flap edema model in the rat was developed based on the inferior epigastric vessels. Significant edema developed after 48 hours. Differing intraoperative doses of methylprednisolone were studied, producing a dose response curve. A single low dose of intraoperative steroid is effective in reducing flap edema; previously recommended doses are probably excessive. PMID- 2243859 TI - A study of the relationship between blood flow and bacterial inoculation in musculocutaneous and fasciocutaneous flaps. AB - Regional nutrient blood flow to musculocutaneous and fasciocutaneous flaps was studied in dogs using 15-microns radiolabeled microspheres, and correlations to bacterial inoculation into closed wound spaces were sought. During the 6-day study period, no differences were found between blood flow to noinoculated versus inoculated flaps. Comparisons of blood flow to the deep surfaces of the flaps showed that blood flow to muscle in musculocutaneous flaps increased rapidly during the first 24 hours and then plateaued, while that to subcutaneous tissue plus fascia in fasciocutaneous flaps demonstrated a gradual and steady increase. The most rapid decline in bacterial counts at the undersurface of both flaps occurred within 24 hours, dropping significantly lower within musculocutaneous flaps. In addition to such surface properties of muscle as tissue ingrowth, rapid early augmentation of muscle blood flow may be largely responsible for superior bacterial suppression observed beneath musculocutaneous flaps. PMID- 2243860 TI - On the genesis and spread of ideas. PMID- 2243861 TI - Split nails. AB - Photographic documentation of successful surgical correction of two major vertical-type and one horizontal-type split nail is presented. The developmental mechanism of the horizontal-type split nail is discussed. Treatment of the vertical-type split nail with bipedicled subperiosteal nailbed-matrix flaps is described in detail. PMID- 2243862 TI - A new surgical approach in genital lymphedema. AB - A new surgical approach has been used in a case of genital lymphedema. After resection of the lymphedematous mass, U-shaped flaps were made from the suprapubic region anteriorly and the posterior scrotal skin posteriorly. The denuded penis was transposed to its original place by passing it through a buttonhole incision made on the anterior flap. The testicles were placed and fixed in pouches prepared between the anterior and posterior flaps. The patient had an acceptable postoperative outcome both in testicular function and habitual sexual activities. PMID- 2243863 TI - Combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap for the repair of wide defects of the lower leg. AB - The tensor fasciae latae musculocutaneous flap has great advantages for reconstruction of the abdominal wall, but the medial border of its territory is limited to the thigh. In order to expand the territory, a combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap was devised. This flap was successfully used to resurface a large defect in the lower leg as a distally based musculocutaneous flap. The advantages of this flap are its extremely large territory, the fact that total necrosis of the flap cannot occur, and that as a proximally or distally pedicled flap it is suitable for large defects in the abdominal wall, lower leg, and gluteal region. PMID- 2243864 TI - Surgical treatment for secondary retracted nose. AB - This surgical technique is presented to correct nasal tip retraction, which is frequently associated with other surgical sequelae that can be corrected simultaneously. It is based on the use of a shield, an anchor, or half an anchor of otocartilage, with one or two posterior supports that are sutured together forming a small L and are fixed to the bed to project the nasal tip and, if necessary, to correct the unilateral or bilateral alar collapse. PMID- 2243865 TI - Simplified technique for isolating vascularized rib periosteal grafts. AB - A modified technique for obtaining a vascularized rib periosteal segment utilizing the posterolateral approach is presented. The technique avoids the inclusion of a large muscle cuff or the pleura around the isolated rib segment and therefore minimizes donor-site morbidity and chest complications previously associated with this approach. PMID- 2243866 TI - Plastic surgery in the early nineteenth century: notes on the collections in the University of Pavia's Museum of History. AB - The authors present the documents of plastic surgery preserved in the University of Pavia's History of the University Museum. They include clinical papers, drawings, surgical instruments, and anatomic preparations. Most of these documents relate to the activity of Luigi Porta, who was a general and plastic surgeon and professor in the Medical School of the University of Pavia from 1832 to 1875. PMID- 2243867 TI - Myocutaneous flaps: who was first? PMID- 2243868 TI - Enlarged photocopies for surface area measurement. PMID- 2243869 TI - Connective-tissue tunnel graft for lymphatic vessel anastomosis. PMID- 2243870 TI - An anomaly in the rat femoral vein. PMID- 2243871 TI - Resection of obstructing inferior turbinates. PMID- 2243872 TI - Plastic surgery for the fetus. PMID- 2243873 TI - The effect of nifedipine on skin flap survival. PMID- 2243874 TI - The second battle of Chesapeake Bay. PMID- 2243875 TI - Does abdominoplasty predispose to pelvic relaxation? PMID- 2243876 TI - Psychiatry and the irrational: does our scientific world view interfere with the adaptation of psychotics? AB - Perhaps even more strongly than others in our contemporary Western world, psychiatrists cling to an exceptionally rigid scientific world view. When psychotic patients speak of such matters as their experiences with spirits or of being possessed or of their preoccupations with meaningful coincidences, psychiatrists discount their views as mere psychotic delusions. We suggest that psychiatrists should deal with their patient's attempts at explaining their symptoms by negotiation and compromise, just as any other physician would do when confronted with patient explanations for symptoms which do not coincide with the tenets of scientific medicine. Rather than relegating the psychotic to a meaning vacuum by dismissing his or her explanations as totally false and non-negotiable, the therapist should help patients find meaning by linking their views and experiences to those of important thinkers within Western cultures. Almost all elements of psychotic thought including beliefs in disembodied spirits, synchronicity (meaningful coincidences), and the possibility of non-material, actions-at-a-distance can be found among respected Western philosophers, psychiatrists, religious leaders and quantum physicists. An example of the world view of a psychotic patient is presented in which a variety of idiosyncratic beliefs are described including convictions of the reality of synchronicity. We demonstrate that highly similar synchronicity beliefs have been entertained by many major Western intellectuals. We contend that on this basis and along with negotiation and compromise, a therapeutic alliance can be established which may provide a measure of symptom relief as well as improvements in rehabilitation potential. PMID- 2243877 TI - Comparison of flurbiprofen and alprazolam in the management of chronic pain syndrome. AB - A three-process model of chronic pain comprising tissue damage, anxiety, and depression is hypothesized. Within this model, the effectiveness of flurbiprofen (for analgesia) plus either alprazolam (for anxiety and depression) or placebo was evaluated in a randomized, double-blind trial with a single crossover. Flurbiprofen was found to have a significant analgesic effect but this was not enhanced by combining it with alprazolam. PMID- 2243878 TI - The use of the general behavior inventory to screen for affective disorders. AB - Accurate diagnosis of affective disorders and of specific subtypes influences treatment decisions about whether to use psychotherapy alone or in conjunction with medication as well as which is the most appropriate choice of medication. The General Behavior Inventory was used to identify unipolar and bipolar subtypes of major affective disorder in consecutive patients in a private practice and to separate them from anxiety and adjustment disorders. This test was significantly more accurate in separating adjustment disorders from unipolar depression than the Beck Depression Inventory which tended to identify depressive symptomatology regardless of diagnosis and to miss bipolar cases. It was found to be superior to other commonly used screening tests for affective disorders in ease of administration, in choice of language, and in specificity. PMID- 2243879 TI - Unemployment and the nature of suicide attempts. AB - The purpose of the study was to compare the perceptions of twenty unemployed and thirty employed British patients recovering from an attempted suicide as regards motives for self poisoning, intent to die, presence of warning, past history of attempts, history of psychiatric treatments, and types of problems reported as antecedents to the suicide attempt. Their key relatives/friends were also interviewed concerning their views of the emergency. Analysis of the responses failed to show significant differences between the employed and unemployed. The implications of these findings as regards further research is discussed. PMID- 2243880 TI - Nicotine addiction in the psychiatric hospital: final report. AB - The following facts are now accepted by everyone with any sense of objectivity. One, that there is an entity known as nicotine addiction and that smoking is such an addiction. Two, that this addiction is related to more preventable deaths than any other disease in the United States. Three, that smoking now causes more deaths from lung cancer among women than does breast cancer. Four, that smoking interferes with the metabolism of the very drugs we use in psychiatry to alleviate symptoms. Five, that smoking is more common among psychiatric patients than in the general population, and more so among the hospitalized mentally ill. This paper, the third in a series, covers the problems encountered in bringing smoking to a complete halt within a psychiatric hospital. It deals with the emotional reactions professional staff had in confronting the problems anticipated and following the results of the effort. It further describes the results which ensued with patients over a one and a half-year period. PMID- 2243881 TI - Defining the role of pet animals in psychotherapy. AB - The literature now contains more than 1000 references to the use of a variety of animals in therapy. The terms used include Pet Therapy, Pet Assisted Therapy, Pet Facilitated Therapy. They reflect lack of agreement as to the role and effectiveness of animal use. Most are anecdotal descriptive studies lacking in scientific methodology. There are almost none in the psychiatric literature despite repeated claims of effectiveness in treating mental and emotional illness. This paper provides a review for the psychiatrist. It describes the development and use of rating scales to generate numerical values for statistical analysis, from videotaped observations of pet therapy sessions. Blind ratings yielded high inter-rater correlations. Although a pilot study, the results indicate the feasibility of designing definitive studies to evaluate the claims of animal enthusiasts. Valuable insights were gained which help to clarify the respective roles of animals and therapists. PMID- 2243882 TI - Psychiatrists' experience of suicide in their patients. AB - Ninety-nine psychiatrists from a defined geographical area were sent a questionnaire asking them to report on clinical, social and demographic characteristics of patients who suicided while under their care. Seventy-three psychiatrists returned the questionnaire and reported having seen a total of 122 suicides. This resulted in a mean of 0.12 suicides per psychiatrist per year of practice. Twenty-four percent of the patients were reported to have had a diagnosis of schizophrenia which is significantly higher than in studies based on coroner's cases. Evidence of withdrawal, considering oneself a burden to others and help negation are factors that had frequently been present in the month prior to the suicide. The authors recommend that these three factors should be examined further by using a prospective strategy. PMID- 2243883 TI - Resolving the conflict of training and therapy in psychiatry. PMID- 2243884 TI - The physical layout of psychiatric offices: a survey. PMID- 2243885 TI - Mental health and abortion: review and analysis. PMID- 2243886 TI - Coadministration of a beta-adrenergic antagonist and a tricyclic antidepressant: a pilot study. AB - After a 7-day washout period, 16 subjects suffering from unipolar depression were randomly assigned to either desipramine (DMI) or DMI plus propranolol treatment for 21 days. Both groups showed a significant improvement in their scores on the Hamilton Rating Scale for Depression (HRSD) after 21 days of drug treatment. However, there was no significant difference in the improvement in HRSD scores between the two groups. The results of this pilot study support the need to reevaluate the popular belief that propranolol induces or worsens depression. PMID- 2243887 TI - Pilocarpine, an orally active muscarinic cholinergic agonist, induces REM sleep and reduces delta sleep in normal volunteers. AB - The effect of oral pilocarpine, a direct-acting muscarinic, cholinergic agonist, on polygraphic sleep parameters was studied in 13 healthy male volunteers. Subjects received placebo and oral pilocarpine (25 mg) in a double-blind, counterbalanced, crossover design. Pilocarpine shortened the latency of rapid eye movement (REM) sleep and increased total REM time, REM%, and the duration of the first REM period. In addition, it reduced Stage 4 sleep and Delta sleep. Pulse rate was not significantly changed during the first hour of darkness after administration of pilocarpine. Subjective sleep experience and the subjects' condition in the morning were not altered. These results suggest that pilocarpine has central effects (i.e., induction of REM sleep) that are similar to those of other centrally acting muscarinic cholinomimetic agents. PMID- 2243888 TI - Is seasonal affective disorder a variant of atypical depression? Differential response to light therapy. AB - Similar symptomatology has been described for both seasonal affective disorder (SAD) and atypical depression. For example, hyperphagia, hypersomnia, and intense lethargy are common to both, suggesting that they might be subtypes of the same disorder. If SAD and atypical depression are different manifestations of the same underlying pathophysiology, treatment effective for one might also benefit the other. Bright artificial lights (2500 lux, 6-8 a.m. and p.m.) were significantly less effective in treating eight patients diagnosed as having atypical depression without a seasonal pattern than 25 SAD patients. Differential treatment outcome suggests that SAD and atypical depression are separate disorders. PMID- 2243889 TI - Melatonin suppression in bipolar and unipolar mood disorders. AB - Nocturnal melatonin suppression to 500 lux light was studied during an acute episode of illness in 8 patients with bipolar disorder, 7 patients with unipolar depression, and 15 age-, sex-, and season-matched normal controls. Unipolar patients did not differ from controls in melatonin suppression. In contrast to previous studies, controls showed greater melatonin suppression than bipolar patients. Baseline melatonin concentration, however, was significantly lower in the bipolar group compared to the unipolar and control groups. PMID- 2243890 TI - Night light alters menstrual cycles. AB - Dewan asserted 20 years ago that a bedside light could shorten and regularize the menstrual cycle among women with long and irregular menstrual patterns. To replicate this, seven volunteers slept with a 100-watt bulb by the bedside from days 13-17 of their menstrual cycles, while nine controls similarly used a dim red placebo (photographic safe light). Indeed, the 100-watt bulbs shortened menstrual cycles from a mean of 45.7 days to 33.1 days and reduced variability, but the placebo had no effect. These results suggest that light may have promise for treatment of infertility, for contraception, and for other endocrine interventions. PMID- 2243891 TI - Effects of bright light on responsiveness to a muscarinic agonist in rats selectively bred for endogenously increased cholinergic function. AB - The Flinders Sensitive Line (FSL) was derived from the Sprague-Dawley rat by selectively breeding those animals exhibiting a high level of sensitivity to an anticholinesterase. The Flinders Resistant Line (FRL) was simultaneously developed as a control line. These lines exhibit nonoverlapping distributions of their thermic responsiveness to oxotremorine. Bright light prevents the development of supersensitivity to oxotremorine occurring as a result of forced stress or treatment with a muscarinic receptor antagonist in the rat. The authors now report that treatment with bright light during the regular photoperiod (i.e., a time that does not produce a phase-shift or free-running) differentially affects the hypothermic response and activity-suppressing effect of oxotremorine in both the FSL and FRL. Both lines exhibit decreased hypothermia without reduction in motor activity in response to oxotremorine following 6 days of treatment with bright light. The magnitude of blunting of the hypothermic response was greater in the FSL than the FRL. These findings suggest that (1) studies of the effects of bright light are contingent on the end point one measures and (2) the capacity of this treatment to blunt the hypothermic response to a muscarinic agonist is greater in an animal model with endogenously hyperactive muscarinic cholinergic systems. PMID- 2243892 TI - Neuroendocrine measures of dopaminergic function in chronic cocaine users. AB - Plasma prolactin (PRL) and growth hormone (GH) levels are determined, in part, by the effects of dopamine (DA) at pituitary and hypothalamic DA receptors, respectively. To determine if chronic cocaine abuse alters dopaminergic activity, basal PRL and GH concentrations were measured in 16 male patients meeting DSM-III R criteria for cocaine dependence (8 cocaine users and 8 cocaine + alcohol users) and 8 normal controls. In addition, the functional responsivity of DA receptors was assessed in the same group of patients by measuring the change in plasma PRL and GH concentrations following the administration of the direct-acting DA agonist, apomorphine (0.01 mg/kg, s.c.) or saline. No difference in basal plasma PRL and GH levels or plasma PRL and GH responses to apomorphine administration was found between the entire group of cocaine patients and normal controls. However, three of the cocaine patients had basal plasma PRL levels that were more than 2.5 SD greater than that of the normal controls, suggesting that some interference of dopaminergic inhibition of PRL secretion might be present in at least some cocaine users. Although baseline plasma PRL levels were elevated in a subgroup of cocaine users, these data do not support the hypothesis that chronic cocaine abuse produces consistent abnormalities in dopaminergic function at the pituitary or hypothalamus. PMID- 2243893 TI - Dopaminergic sensitivity and cocaine abuse: response to apomorphine. AB - Ten male patients with chronic cocaine abuse received a single dose of the dopamine agonist apomorphine. Self-ratings of cocaine craving, depression, and anxiety decreased in response to apomorphine. Neuroendocrine response was consistent with central dopaminergic stimulation. Patients in the "craving" phase of the cocaine abuse cycle differed in behavioral but not neuroendocrine response to apomorphine from patients in the "crash" phase. Decrease in cocaine craving correlated with decrease in plasma homovanillic acid (pHVA). Total cocaine consumption correlated negatively with baseline prolactin and pHVA levels and inversely with peak change in prolactin following apomorphine. Patients had blunted neuroendocrine response to apomorphine in comparison to historical normal controls. Implications for the "dopamine" hypothesis of cocaine abuse are discussed. PMID- 2243894 TI - Correlates of rapid neuroleptic response in male patients with schizophrenia. AB - Correlates of neuroleptic response latency were assessed in 16 male schizophrenic inpatients during 4 weeks of fixed dose (20 mg/day) haloperidol treatment. Rapid responders showed a mean 40% reduction in Brief Psychiatric Rating Scale (BPRS) positive symptom scores by day 10 of treatment. Rapid responders had significantly lower plasma homovanillic acid (pHVA) concentrations compared to non-rapid responders during week 4 of haloperidol treatment. However, rapid versus non-rapid responders did not differ with respect to demographics, baseline positive or negative BPRS symptom scores, performance on tests of neuropsychological function, or mean plasma haloperidol concentrations. PMID- 2243895 TI - Attentional markers of vulnerability to schizophrenia: performance of medicated and unmedicated patients and normals. AB - Medicated and unmedicated schizophrenic patients (both n's = 14) were compared to a normal control sample (n = 15) on two attentional tasks hypothesized to be markers of vulnerability to schizophrenia. These tasks, the continuous performance test and the visual backward masking task, were found to be more deviant in schizophrenic patients than in normals. In addition, the group mean levels of performance did not differ consistently across medication status within the medicated patients. It was found, however, that the association between these tasks varied as a function of medication status, with unmedicated patients more similar to normals than to medicated patients. The implications of these results for the two tasks as markers are discussed, with special focus on those earlier studies that did not evaluate unmedicated patients. PMID- 2243896 TI - Effects of serotonin antagonists on m-chlorophenylpiperazine-mediated responses in normal subjects. AB - The serotonin (5HT) agonist, m-chlorophenylpiperazine (MCPP), has been used as a challenge agent to assess central 5HT receptor sensitivity in normal subjects and patients with panic disorder, obsessive-compulsive disorder, and major depression. Adrenocorticotropin, cortisol, and prolactin responses to MCPP were among the variables measured. MCPP's usefulness as a probe of 5HT receptors, however, hinges on its 5HT selectivity. To address MCPP's selectivity for 5HT, this study tested whether two different 5HT antagonists, methysergide (4 mg p.o.) and metergoline (4 mg p.o.), could block the hormonal and behavioral effects of MCPP (0.5 mg/kg p.o.) in 10 normal male subjects in comparison to placebo. Both 5HT antagonists abolished the prolactin release to MCPP. Metergoline, the antagonist with the more potent 5HT binding affinity, significantly blocked MCPP's effect on cortisol release as compared to placebo, and methysergide showed a nonsignificant trend to that effect. MCPP alone did not have a significant effect on behavioral variables, perhaps explaining why neither 5HT antagonist affected these measures. The findings from this study suggest that both MCPP induced prolactin release and cortisol release are indeed 5HT-mediated effects. PMID- 2243897 TI - Differences in heart rate and blood pressure in children with conduct disorder, major depression, and separation anxiety. AB - Heart rate and blood pressure of children and adolescents admitted to a psychiatric hospital were compared among those diagnosed conduct disorder, major depressive disorder, and separation anxiety disorder. Subjects with conduct disorder had a lower heart rate compared to subjects without a conduct disorder diagnosis; and subjects with separation anxiety disorder had higher heart rate and systolic blood pressure compared to subjects without an anxiety disorder diagnosis. Subjects with major depressive disorder had higher systolic blood pressure than subjects with conduct disorder but no difference in heart rate. The findings are consistent with conduct disorder being associated with decreased noradrenergic function and anxiety/depressive disorder being associated with increased noradrenergic function. PMID- 2243898 TI - Comparisons of males and females with DSM-III dependent personality disorder. AB - To determine whether DSM-III dependent personality disorder (PD) differed in males and females, 30 females and 11 males with this diagnosis were selected from a psychiatric outpatient population. Standardized measures of Axis I, Axis II, and family history were used. There were no differences in age or in the prevalence of Axis I or Axis II disorders in males and females, indicating that females were probably not misdiagnosed as having dependent PD. However, relatives of males had significantly more major depressive disorder and DSM-III anxious personality disorder cluster, while relatives of females had significantly more panic disorder. This may indicate different predisposing factors to dependent PD in males and females. PMID- 2243899 TI - Platelet MAO activity in personality disorders and normal controls. AB - Platelet monoamine oxidase (MAO) activity has been related to several psychiatric disorders and personality dimensions. The purpose of this study was to measure platelet MAO activity in personality disorders and determine its relationship to symptoms analogous to sensation seeking. Twenty-eight males admitted to a psychiatric unit with a DSM-III-R diagnosis of personality disorder were compared to normal controls. Patients with Axis I diagnoses other than adjustment disorder were excluded. There was no difference in MAO activity between patients and normals, although it was lower in borderline patients. MAO activity was inversely correlated with sensation seeking, especially in the patient group, as predicted. The results are consistent with the view that platelet MAO activity is a marker of general psychopathology. PMID- 2243900 TI - Discerning the latent structure of hypothetical psychosis proneness through admixture analysis. AB - The application of psychometric procedures to a normal population sample to detect individuals with increased liability for schizophrenia is a useful methodological adjunct to the traditional genetic high-risk strategy. A necessary and reasonable step in the process of establishing the utility of a viable psychometric index of schizotypy is the formal investigation of the latent structure of psychometric values. The present study used admixture analysis to examine the distribution of scores on the Perceptual Aberration Scale (PAS), an objective measure of hypothetical psychosis-proneness, in a randomly ascertained sample of 18-year-old university students (n = 707). We applied parametric methods that assumed normally distributed component distributions; viewed in this context, our results are hypothesis-generating and not definitive confirmation of specific hypotheses. Within our methodological framework, the results provide strong evidence for the commingling of normal distributions, even after allowing for unequal variances across components and after removing skewness. The overall distribution of power-transformed data is consistent with the existence of three qualitatively distinct classes of PAS responders. We discuss our results in light of Meehl's model of schizotaxia, a "mixed model" of inheritance of liability to schizophrenia, and we review the methodological implications of our findings for future research. PMID- 2243901 TI - Plasma HVA, tardive dyskinesia and psychotic symptoms in long-term drug-free inpatients with schizophrenia. AB - Plasma homovanillic acid (pHVA) levels were measured in 16 chronically ill patients with schizophrenia who also suffered from tardive dyskinesia, and in a group of 14 chronically ill patients with schizophrenia who did not have tardive dyskinesia. All patients were studied following an extensive drug-free period (mean = 32.9 months). Patients with orofacial dyskinesia had significantly lower levels of pHVA than did controls. In patients without tardive dyskinesia, pHVA levels were significantly correlated with both positive and negative symptomatology. In contrast, pHVA levels from patients with tardive dyskinesia bore neither a significant nor a nearly significant relationship to symptomatology. The implications of these findings for dopaminergic models of tardive dyskinesia are discussed. PMID- 2243902 TI - Growth hormone response to growth hormone releasing hormone in depression and schizophrenia. AB - Growth hormone releasing hormone, a 44-amino acid peptide (GHRH-44), was administered (1 micrograms/kg i.v.) to 6 normal controls, 10 schizophrenic subjects, and 7 depressed subjects. A significantly lower growth hormone (GH) response was found in the schizophrenic and depressed groups. Two molecular forms of GH, 22K GH and 20K GH, were also measured but did not further differentiate the three groups of subjects. PMID- 2243903 TI - Does the pretreatment polysomnogram predict response to cognitive therapy in depressed outpatients? A preliminary report. AB - Although several studies reveal that cognitive therapy effectively remediates depressive symptoms in many unipolar nonpsychotic depressed outpatients, the question as to which depressions respond to cognitive therapy remains unanswered. We hypothesized that patients with reduced rapid eye movement (REM) latency (less than or equal to 65.0 min) before treatment would be less likely than those with nonreduced REM latency (greater than 65.0 min) to respond to cognitive therapy. The rationale for this prediction was that endogenous depressions are more likely to exhibit this abnormality and also tend to respond to tricyclic antidepressant medication. Thus, we queried whether these depressions might also respond less to a psychosocial intervention. To date, 39 outpatients with nonpsychotic, unipolar major depression (by the Schedule for Affective Disorders and Schizophrenia Lifetime Version and Research Diagnostic Criteria) who score at least 14 on the 17-item Hamilton Rating Scale for Depression have completed this project, which is still in process. Preliminary findings do not suggest a systematic relationship between pretreatment REM latency and response to cognitive therapy. Further, these results suggest that at least some patients with biological dysregulation, as indicated by reduced REM latency, show a favorable response to an acute trial of cognitive therapy. Study limitations include a small sample of patients who exhibit extremely reduced REM latencies (less than or equal to 51.0 min) and a small number of endogenous depressions. Data collection continues. PMID- 2243904 TI - Plasma amino acids in attention deficit disorder. AB - This study examines plasma amino acids in a group of 28 patients meeting DSM-III criteria for attention deficit disorder (ADD) and 20 control subjects. Compared with controls, the ADD subjects had significantly lower levels of phenylalanine, tyrosine, tryptophan, histidine, and isoleucine. These data suggest a general deficit in amino acid transport, absorption, or both. PMID- 2243905 TI - Decreased somatostatin-like immunoreactivity in the cerebrospinal fluid of chronic schizophrenic patients with cognitive impairment. AB - The level of cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for 11 chronic schizophrenic patients with moderate cognitive impairment and for 8 controls. The CSF SLI was significantly reduced (37%) in schizophrenic patients, but this decrease did not correlate with the degree of cognitive decline measured by the Mini-Mental State Examination, with psychotic symptoms estimated by the Brief Psychiatric Rating Scale, or with the neuroleptic dose. Although a reducing effect of long-term neuroleptic treatment cannot be totally excluded, the present study suggests that the CSF SLI level is decreased in cognitively impaired schizophrenic patients, as in many other disorders with cognitive impairment. PMID- 2243906 TI - Polysomnographic findings in adolescents with major depression. AB - Ten adolescents with major depression and 10 age-matched controls were studied with polysomnography for 3 consecutive nights. The sleep records were analyzed for variables pertaining to sleep continuity (total sleep time, sleep efficiency, sleep onset latency, number of awakenings, and number of stage shifts), sleep architecture (Stages 1, 2, 3, and 4), and rapid eye movement (REM) sleep (total) REM sleep time, number of REM periods, REM latency, and REM density). The experimental and control groups were compared on 14 variables with the t test for independent groups. The results indicated that none of the sleep variables differed significantly between the two groups. These results confirm earlier findings indicating that the abnormalities in REM latency and REM density that characterize adults with major depression are absent in adolescents suffering from major depression. Developmental and diagnostic variables are discussed as possible explanations for the sleep differences between adolescents and adults with depressive disorders. PMID- 2243907 TI - Thyroid function in psychotic depression. PMID- 2243908 TI - [The difficult path of critical psychosomatic medicine]. AB - In our present-day society that openly worships strength and secretly represses death, psychosomatic medicine is on the horns of a dilemma: either to externalize this repressive attitude and thus to translate it into reality so to say by de interiorization, or to critically defend a mental health concept that can be considered as representing a unification of inner and outer ecology. PMID- 2243909 TI - [The pioneer days of psychotherapy and psychosomatic medicine]. AB - The author describes the psychotherapeutic method of a forgotten pioneer Paul Dubois in the beginning of the century. He points out the difference with the modern Pioneer Walter Brutigam. PMID- 2243910 TI - [Psychosomatic medicine -- does it have the right to exist as a separate discipline?]. AB - In their "Recommendations for Clinical Research at Medical Schools and Universities" (1986), the Scientific Council of the Federal Republic of Germany described the quantity and quality of psychosomatic and psychotherapy-research generally as unsatisfactory. Although meanwhile in some fields, such as epidemiologic longitudinal studies, comparative therapy evaluation of controlled individual case studies, research has reached good-quality standard, essential deficits still remain. There are several reasons for the delay in implementing psycho-somatic-psychotherapeutic research after the establishment of departments of psychosomatic medicine and psycho-therapy at Medical Schools in the Federal Republic of Germany in 1970. For example 1.) psychosomatic research covers almost all disciplines of clinical medicine. Therefore, a variety of special knowledge is required. 2.) Global psychological theories that marked the beginning of psychosomatic medicine are obviously inadequate in providing useful approaches to causal explanations in psychosomatic medicine. The cultural complexity of mental life determining the substance of psychoanalytical hypo-theses is apparently not reflected in the comparatively simple, phylogenetically rooted psychic factors leading to pathophysiological processes. As a consequence, psychosomatic research will have to concentrate less on global theories and to focus more on heuristic models of limited range specific to the respective functional systems or illnesses. The need to carry out examinations on both mental and physical level requires knowledge of either methodology. In addition, the necessary access to patients and laboratories suggests that psycho-somatic departments should be closely connected with those of internal medicine or one of the other departments with many psychosomatic problems. Research and advanced training in psychotherapy, on the other hand, should be performed in close cooperation with the one department responsible for research and the provision of care for the mentally ill, with psychiatry. Thus it would be possible to definitely improve the present situation, which is characterized by an overburden of the usually small departments of psychosomatic medicine and psychotherapy with matters of psycho-therapeutic training, research training, clinical work and teaching. At any rate, psychosomatic medicine is having great prospects, in particular concerning research. The departments of psychosomatic medicine and psychotherapy should be better prepared and equipped for these future tasks. PMID- 2243911 TI - [The future of psychosomatic medicine in West Germany--an illusion?]. AB - Due to historical developments the structure and function of German Psychosomatics is unique in the world. Hence, to predict its future is difficult. There is the intimate conjunction of psycho-somatics with psychotherapy and the mandatory teaching of this combination to medical students, so that every medical school has to have a corresponding department and that most of these are psychoanalytically orientated. Medical care insurances finance psycho-therapy to a degree unknown in any other country. Then, in excess of the 700 beds for psychosomatics/psychotherapy in university and communal hospitals, the FRG provides another 4000 beds which are legally, financially and geographically separated from the former. Epidemiological data show that in spite of the above average out-patient financing many patients in need are not treated psychotherapeutically until their working capacity is reduced by which they become subject to another (and separate) legal system: The law of rehabilitation the measures of which are financed by the federal or state pension funds. At this late stage only in-patient psychosomatic treatment has some chance of rehabilitation. Hence, in cooperation with private entrepreneurs or non-profit organizations the above-mentioned over 4000 additional beds were provided. Two examples show that the effects of psychotherapy with somatic illness (myocardial infarction and metastatic cancer) are remarkable but discrete and their full impact can only been seen after several years. These features probably explain the habitual underestimation of psychotherapy in medicine. PMID- 2243912 TI - [10 years of the psychosomatic department at a general hospital -- retrospect and perspectives]. AB - The psychosomatic department of the Neurenberg City Hospital--a general hospital of 2,600 beds--has been existing since 1980 as an independent department within a center of neurology and psychiatry. The department's functions comprise the indoor psychosomatic-psychotherapeutic care, a liaison and consultation service, the training of interested members of the hospital's medical and nursing staff and the post-graduate training of physicians working in private practice for an additional psychotherapist's title. At present these functions are met by 7 physicians, 4 psychologists, 3 social workers with special training, 1 concentrative motion therapist and 10 nurses. A staff expansion is necessary and scheduled. As for the contents, the work is characterized by an integrative therapeutic approach: As first consequence of such an integrative approach the consultation field has to have predominance. As a second consequence the consultation field has to be established and expanded as a staff-centered liaison service and not primarily as a patient-centered consultation service. As a third consequence the training of the hospital's medical and nursing staff becomes necessary. PMID- 2243913 TI - [Changes of the family in the 20th century]. AB - This article deals with the changes in socialisation patterns and adaptation to the conditions imposed by society, in internal familiar structures, and in the general attitude to life, that took place in the course of our present century. The empirical basis of this study was supplied by an investigation conducted with students of medicine representing three generations, i.e. persons born in 1905, 1934 and 1962. Against the background of the sociocultural and economic developments that took place in the Federal Republic of Germany, emphasis is on the following points: 1. The father of the family has been deprived of his power, and women have developed a new self-understanding; 2. the generation barriers are no longer impenetrable; 3. the family as such has lost a great deal of its functional importance due to the institutionalisation of care and welfare aspects. PMID- 2243914 TI - [Psychosomatics of the family today]. AB - The concept "family psychosomatics" was introduced some 30 years ago. It denoted at that time a programme rather than a domain of practice and research. Today this domain increasingly reflects a systemic approach focussing on the so-called "problem defined system" which is not necessarily identical with the family system. Also, we notice that systems with serious psychosomatic disorders tend to embed themselves in a "hard reality". Therefore, therapeutic interventions should aim at softening this hard reality. In this, they could make use of a "systemic questioning" which can trigger changes, and at the same time, can anticipate potentially frightening consequences of such changes. PMID- 2243915 TI - [The psychosomatic consultation and liaison service. Evaluation, research approach and contribution to education]. AB - Consultation and liaison work is one of the major fast growing fields of psychosomatic medicine in the Federal Republik of Germany. According to basic principles "integration by cooperation or by increasing psychosocial competence", we try to psychologize medicine as practized in the hospital. Results from a psychooncological study shown an urgent need for further research especially concerning process studies. The importance of CL-work for medical students' training is demonstrated with different examples. PMID- 2243916 TI - [Psychotherapy motivation and psychotherapy acceptance. Initial results of the Mannheim intervention study]. AB - In our controlled longitudinal study of a representative high-risk sample of psychogenically impaired individuals, within a multidimensional model of mental health, the variables "life event", "social support" and "personality" are examined concerning their analysis of variance and their interdependence. We assume that a therapeutic influence on the variable "personality" causes a modified risk of becoming psychogenically impaired, and intend to prove this in terms of the altered maturity of defenses, the improved ego-functions, but also in terms of the improvement of the social network and the rarer constellation of critical life events. The modified effect on the variable "personality" is a differential offer of psychoanalytic therapy. By means of our instruments of investigation we tried to clarify if the acceptance of psychotherapy offered to resp. the motivational situation of our probands in regard to a psychotherapy covariates with certain sociodemographically or depth psychologically measurable personality patterns. There was a trend towards accepting the offer of therapy in case of high psychical and socio-communicative psychogenic impairment and in case of relatively high frankness on the FPI scale. The acceptance of an offer of therapy correlated highly significantly with the frankness scale of the Bond questionnaire extended for several defense items. The implications of this finding are discussed. PMID- 2243917 TI - [Psychoanalysis in the north-south conflict]. AB - The limitations and possibilities of psychoanalysis in a public health service are presented and discussed based on a report on the public health system in Nicaragua which has been built up consistently in cooperation with psychoanalysis since the fall of the Somoza regime in 1979. The largely successful experiment of integrating psychoanalytic thought into medical training and medical care in a country of the so-called third world has instigated reflections on the present situation in the Federal Republic of Germany. The hypothesis is discussed as to how conflict avoidance, dominant scientific criteria and the extent of political consciousness have contributed to the lacking cooperation between psychoanalysis and medicine. PMID- 2243918 TI - [Therapeutic factors of inpatient psychotherapy--the patients' view]. AB - Inpatient psychotherapy as a complex treatment program coordinates a multitude of specific, possibly therapeutic helpful components. At least in departments of about 20 or more beds the available therapeutic components are composed or dosed in a different kind for certain groups of patients (indication). In the Psychosomatic Clinic with a ward of 22 beds patients with certain psychoneurotic symptoms, bodily dysfunction or psychosomatic illnesses take part in different inpatient psychotherapy programs for 3 months. This very intensive treatment phase is regularly followed by an outpatient psychoanalytic oriented individual or group-psychotherapy for 1 or more years. For the inpatient treatment phase we differentiate 18 possibly therapeutic helpful factors. Preparing systematic studies we asked the patients at the end of their inpatient treatment phase to judge: to what extent the 18 single factors were helpful. Furthermore a personality questionnaire (Giessen-Test) and a checklist of complaints (Giessen Checklist of Complaints) were routinely filled out by the patients pre and post their inpatient time. From this data we derive independent success-scores which enables us to investigate the association between the subjective assessment of the helpfulness of certain therapeutic factors and somewhat independent criterions. The given data of n = 291 patients allow a empirically based discussion of the question: "What relevance do certain components of inpatient psychotherapy alone or together with other components have for certain groups of patients or specific settings? PMID- 2243919 TI - [Theodora R.--case report on the topic of transitional object, pathologic grief and catharsis]. AB - The author presents a case report, following Volkan, who developed the re-grief therapy. In the second part of his paper there are shown connections to the studies of hysteria by Breuer and Freud. PMID- 2243920 TI - [Deglutition anxiety. Consideration of symptoms and psychodynamics of heart phobia]. AB - Fear of swallowing as an accessory symptom or symptomatical precursor of heart phobic development is pointed out along two short casuistic reports. In highly regressive states fearful inhibition of the act of swallowing proper occurred in relation to food and even own saliva. The symptom is discussed before the background of separation conflicts and pathological internalization processes with confusion of self- and object-representations in heart-phobic patients. The author argues that an understanding of this symptom provides insight into the- inspite of phobic phenomenology--essentially hypochondriac psychodynamics of heart-phobic patients with narcissistic traits in particular. PMID- 2243921 TI - [Psychodynamic approach to understanding unprotected sexual intercourse of HIV positive patients]. AB - Despite good knowledge about the transmission of HIV, not all HIV-carriers are consequently using condoms. Three case-studies are presented. A psychodynamic approach is presented containing two hypotheses: (1) The more condom use is experienced as separating the two partners and actualizing their different perspectives for the future, the less consequent will condom use be. (2) The more "sexualization" is working as a defense mechanism against depressive or narcissistic crises, the less protection and concern for the partner will control sexual behavior. Psychotherapeutic implications are discussed. PMID- 2243922 TI - [William Hunter and the medical world of his time]. PMID- 2243923 TI - The convergence of behaviourism and logical positivism. PMID- 2243924 TI - The history of algology, algotherapy, and the role of inhibition. AB - Cephalalgia (1st century AD), nostalgia (1678), neuralgia (18th century), causalgia (1872) were terms followed in the 1950's by Bonica's 'algology... a disease state of its own', addressed by ever-growing numbers of pain clinics, strongly foreshadowed by Leriche's douleur maladie in the 1930's. (Hence also 'algotherapy'). Philosophers first, then early academic physiologists began to exhibit interest in pain, that all too common phenomenon, only too often unyielding to theoretical as well as practical efforts. Was it, after all, an instance of built-in self-preservation, a reflex? Identification of the nervous energy and its anatomical pathways in the 19th century, endless arguments as to their 'specificity', led to new surgical attempts to control and interpret pain, by now supported by general, then local anesthesia. Early in this century Henry Head's much-discussed notion of 'epicritic' sensation exerting some control over 'protopathic' pain was soon followed by Otfried Foerster's insistence on a central role of inhibition providing pain relief. Almost forgotten, Foerster's idea found expression in Melzack and Wall's 'gate control theory' of 1965. Gasser and Erlanger's classification of sensory nerve fibers began to dominate research in the 1930's thanks to the cathode ray oscillograph invented in 1897. The pain inhibition concept was given another boost in the seventies when the role of the midline mesencephalic and oblongata nuclei was established as both opium receptors and producers of opioids. Finally, inhibition may also be seen as the principle underlying the age-old therapeutic effect of 'counter-irritation', mostly in the form of electrical stimulation. PMID- 2243925 TI - [The epiglottis in antiquity in medicine and philosophy]. AB - In Antiquity, the epiglottis and the related question whether drink enters the lung is a problem embracing both differently organized philosophical strategies and differently developed medical competences. Over the centuries, the history of a physiological question gradually turns into a debate where we find philosophers disagreeing with philosophers and physicians with physicians. A peculiar feature of this debate is that from a certain time on it involves a division between those who defend Plato's view on the subject and those who (philosophers as well as physicians) criticize it. Plato, Aristotle and Chrysippus, the Hippocratic authors and Erasistratus in the testimony of Aulus Gellius, Plutarch and indirectly also of Cicero, and then Galen and Macrobius have a special place in the development of this topic. PMID- 2243926 TI - Tooth fracture reattachment: case reports. PMID- 2243927 TI - An alternative procedure for canine fixed partial denture retainers. PMID- 2243928 TI - The combination acid-etch-retained splint in fixed precision complete-coverage partial denture abutments. PMID- 2243929 TI - Stress-equalizing removable partial denture. PMID- 2243930 TI - Assessment of microleakage of three dentinal bonding systems. PMID- 2243931 TI - A scanning electron microscopic investigation on the acid-etched cervical margin of Class II cavities. PMID- 2243932 TI - Replacement of amalgam restorations that have marginal defects: variation and cost implications. PMID- 2243933 TI - Orthodontic positioning of an impacted supernumerary tooth: report of a case. PMID- 2243934 TI - Improving marginal adaptation of provisional restorations. PMID- 2243935 TI - Exposure to dental radiation--a perspective. PMID- 2243936 TI - Quadrant iatrodontics: a technique for removing overhangs. PMID- 2243937 TI - Dual-path removable partial denture treatment for Class IV edentulous patients with deficient canine cingula. PMID- 2243938 TI - Periodontal considerations in the treatment of dilacerated maxillary incisors. PMID- 2243939 TI - Primary and permanent incisor twinning defects in one dental quadrant: report of a case. PMID- 2243940 TI - Effect of insertion technique on microleakage in mesio-occlusodistal composite resin restorations. PMID- 2243941 TI - The tensile bond strength of resin-bonded, electrolytically etched alloy to enamel. PMID- 2243942 TI - Surface alteration of composite resins after curette, ultrasonic, and sonic instrumentation: an in vitro study. PMID- 2243943 TI - Surgical templates for the placement of osseointegrated implants. PMID- 2243944 TI - The effect of vision on craniocervical posture and its relation to craniofacial and dentoalveolar morphology. PMID- 2243945 TI - The 100-year dilemma: what is a normal occlusion, and how is malocclusion classified? PMID- 2243946 TI - The collimation and film speed mystery in dental radiology: what does it take for a dentist to change? PMID- 2243947 TI - Adhesion promotion by chemomechanical preparation of dentin. PMID- 2243948 TI - Composite resin and glass-ionomer cement: current status for use in cervical restorations. PMID- 2243949 TI - Treatment of posterior crossbite in the primary and early mixed dentitions. PMID- 2243950 TI - The prevalence of oral manifestations of systemic lupus erythematosus. PMID- 2243951 TI - A technique for the construction of complete dentures in two visits. I. Clinical and laboratory procedures. PMID- 2243952 TI - Effects of zirconium silicate chewing gum on plaque and gingivitis. PMID- 2243953 TI - Effects of fluoride pretreatment on bond strength of a resin bonding agent. PMID- 2243954 TI - Failure mode of a posterior composite resin bonded to a glass-ionomer cement treated with various etching times and with or without a coupling agent. PMID- 2243955 TI - A clinical trial of the glass-ionomer cement-composite resin "sandwich" technique in Class II cavities in permanent premolar and molar teeth. PMID- 2243956 TI - An in vitro evaluation of five dentinal adhesives in posterior restorations. PMID- 2243957 TI - Arthritis: roles of radiography and other imaging techniques in evaluation. AB - Imaging studies are performed on patients with arthritis for a variety of reasons: to determine whether an arthritic condition is present; to establish the specific diagnosis; to determine the extent of disease; to assess the activity of disease; to detect complications of disease; to evaluate progression of disease; to judge the efficacy of drug treatment; to help in selection of surgical candidates; to aid in the choice of surgical procedures; to size, design, or fabricate prostheses; and to identify complications of surgery. Conventional radiography is still the mainstay of all examinations in arthritic patients. Arthrography is best applied to evaluate complications of disease and of surgery, although it may be useful in disease detection and in determining the specific diagnosis. Nuclear medicine studies are best used to identify complications of surgery and may also be useful to assess disease activity or extent. Ultrasound is useful to detect dissecting synovial cysts and deep venous thrombosis. The most valuable role of computed tomography is in the design and fabrication of prostheses and in evaluating complex anatomy of involved joints. Magnetic resonance imaging may be useful in early detection of articular cartilage damage and may assist in determination of the specific diagnosis; enhancement with contrast material may aid in assessment of disease activity. PMID- 2243958 TI - Quality assurance in a nuclear medicine department. AB - This article reviews the general principles of quality assurance (QA) in an imaging department, with emphasis on nuclear medicine. The various steps taken during the development of the QA program reflect the response of the QA committee as it came to a better understanding of the components of QA. Accrediting and regulatory bodies have had important roles in providing guidance. Quality control of instrumentation and radiopharmaceuticals opened the gateway to monitoring in high-volume, high-risk areas; however, QA expanded this concept into better generic and clinical monitoring. Encouragement of the use of quality of care referral forms resulted in greater participation by all members of the department. Examples of physicians' QA activities include double reading of images and sending of code cards. Experience with other forms of physician QA activities is also included. The QA committee provides a forum for five steps of QA: identify problems, assess the causes, implement action to prevent them, monitor effects of the actions, and document these activities. These steps should lead to improvement in the standards of patient care. PMID- 2243959 TI - Imaging of acute stroke. PMID- 2243960 TI - Complementary roles of PET and MR spectroscopy in the management of brain tumors. PMID- 2243961 TI - Early cerebral infarction: gadopentetate dimeglumine enhancement. AB - Gadopentetate dimeglumine was administered prospectively to 50 patients who presented for magnetic resonance (MR) imaging within 2 weeks after a cortical cerebral infarction. Twenty-two patients (44%) were imaged within 3 days after clinical ictus. Abnormalities detected with gadopentetate dimeglumine enhancement were observed in 46 (92%) of 50 patients. Classic parenchymal enhancement was a late finding, observed in all patients (17 of 17) imaged at 7-14 days after infarction. Before this time, three additional phases of contrast material related abnormalities were observed. Enhancement of vessels supplying the infarct ("intravascular enhancement sign") was the earliest finding, seen in 17 (77%) of 22 infarcts aged 1-3 days. From day 2 to day 6, abnormal enhancement of meninges adjacent to the infarct was frequently noted ("meningeal enhancement sign"). Finally, a transition phase that combined intravascular or meningeal enhancement with early parenchymal enhancement was seen from day 3 to day 6. Gadopentetate dimeglumine-enhanced MR imaging in early stroke reveals evidence of vascular engorgement and sluggish flow, which precede the development of classic parenchymal enhancement. PMID- 2243962 TI - Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET. AB - Localized hydrogen-1 magnetic resonance (MR) spectroscopy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were employed to obtain metabolic information from intracranial gliomas. Advantages and difficulties associated with comparison of results from the two modalities were realized. Forty patients were studied with H-1 MR spectroscopy. MR signal intensities from lactate, N-acetylaspartate (NAA), choline, and creatine from a volume of interest containing the tumor and a contralateral volume were obtained and evaluated. NAA signal intensities were generally decreased in the tumor spectra, and choline signal intensities were elevated. H-1 MR spectroscopy was unsuccessful in eight patients, and FDG PET scans were not obtained in four of the patients with successful MR spectroscopic examinations. Lactate signal intensity was detected in 10 of the 28 patients who had successful H-1 MR spectroscopic and FDG PET studies. Lactate signal intensities were observed in lesions shown at FDG PET to be hypermetabolic, as well as in lesions found to be hypometabolic. PMID- 2243963 TI - Chemical shift imaging of human brain: axial, sagittal, and coronal P-31 metabolite images. AB - Multivoxel magnetic resonance (MR) spectroscopy and novel data analysis techniques were developed to obtain high-quality phosphorus-31 metabolite images from the human brain and to overlay each metabolite distribution directly onto corresponding hydrogen-1 MR images. The P-31 MR spectroscopic data were acquired by means of three-dimensional chemical shift imaging (phase encoding in three spatial dimensions) on a 1.5-T clinical instrument equipped with a specially designed quadrature P-31 birdcage coil constructed in the authors' laboratory. Axial, sagittal, and coronal metabolite images based on the area for any one of five peak regions (phosphodiester; phosphocreatine; gamma, alpha, and beta adenosine triphosphate) were generated from 8 X 8 X 8 or 12 X 12 X 8 CSI arrays with voxel sizes of 27 cm3 and 12 cm3, respectively. The positions of these images were aligned with anatomic features by means of the voxel-shifting capability of the Fourier transform. Direct overlays of these metabolite images on corresponding proton images demonstrated excellent correlation with anatomy, factors indicating the utility of this technique for viewing P-31 metabolite levels in all areas of the brain simultaneously. PMID- 2243964 TI - Embolization with particles in thoracic intramedullary arteriovenous malformations: long-term angiographic and clinical results. AB - To evaluate the long-term results of endovascular treatment with particles in the management of thoracic intramedullary arteriovenous malformations (AVMs), the authors retrospectively reviewed the angiographic and clinical findings in 35 patients. Follow-up was 1-15 years (mean, 6 years) in 28 patients and 6-10 months (mean, 7 months) in seven. A total of 158 embolization procedures were performed in 35 patients. Revascularization occurred frequently, necessitating multiple endovascular sessions. Long-term clinical evaluation showed clinical improvement, compared with the initial status before treatment, in 63% of the patients. Clinical aggravation due to embolization was observed in seven patients (20%) after 12 of the 158 endovascular sessions (8%). These results are better than those reported after surgery and indicate that embolization with particles is an efficient and safe tool in the treatment of thoracic intramedullary AVMs. PMID- 2243965 TI - Fourier analysis of cerebrospinal fluid flow velocities: MR imaging study. The Scandinavian Flow Group. AB - An interleaved pseudocinematographic FLASH (fast low-angle shot) sequence with additional pulsed gradients for flow encoding was used to quantify cerebrospinal fluid (CSF) flow velocities and CSF production. Flow-dependent phase information was obtained by subtracting two differently encoded phase images. The phase information in the resultant image was converted to flow velocity with a calibration curve with the slope 26.5 radian.m-1.sec. The velocity versus time function was Fourier transformed and a continuous curve was fitted to the measured data with use of the first three harmonics. The in vivo measurements showed a significant variation in flow velocities in the cerebral aqueduct (range, 6-51 mm/sec). Calculated CSF production was in the range of 0.6-1.2 L/24 h. The present method gives valuable information about CSF hydrodynamics in an imaging time of less than 8 minutes. PMID- 2243966 TI - Parotid gland: plain and gadolinium-enhanced MR imaging. AB - The purpose of this study was to show the typical appearance of lesions of the parotid gland with plain MR imaging and MR imaging enhanced with gadopentetate dimeglumine. Seventeen patients with inflammatory changes and 43 with benign and malignant tumors were studied. The examinations were carried out with plain T1 weighted sequences with a repetition time (TR) of 500 msec and an echo time (TE) of 25 msec (TR/TE = 500/25), T2-weighted sequences (1,600/90), and gadolinium enhanced T1-weighted sequences in axial, coronal, and sagittal orientations. For identifying normal anatomic structures such as the facial nerve and the main duct, the administration of gadopentetate dimeglumine was helpful. In inflammatory changes, gadolinium-enhanced images showed no diagnostic advantages. Gadopentetate dimeglumine proved helpful in delineating tumorous lesions and in differentiating benign and malignant lesions. However, an exact differentiation of the different histologic types was not possible. Post-operative fibrosis could be differentiated from recurrent tumors after administration of gadolinium. If a question regarding infiltration or definition of the boundaries of a lesion cannot be answered with non-enhanced MR imaging, gadopentetate dimeglumine administration is advised. However, for routine imaging of the parotid gland, its use is not recommended. PMID- 2243967 TI - Graves orbitopathy: correlation of CT and clinical findings. AB - The clinical and high-resolution computed tomographic (CT) findings in 71 patients (142 orbits) with Graves orbitopathy and 20 healthy patients (40 orbits) were retrospectively reviewed. The orbits with orbitopathy were subgrouped at clinical examination into those with (n = 18) and those without (n = 124) optic neuropathy. Mean extraocular muscle diameters and the calculated muscle diameter index were significantly increased in all orbits with ophthalmopathy, particularly in those with optic neuropathy. Graves orbitopathy affected the superior muscle group (63.4%) more than the medial (61.3%) or inferior (57%) recti. The most common pattern of muscle involvement involved all five measured extraocular muscles. Solitary muscle involvement most frequently involved the superior muscle group (6.3%). Significant enlargements of the retrobulbar optic nerve sheath and superior ophthalmic vein were noted only in orbits with optic neuropathy. Anterior displacement of the lacrimal gland at CT correlated with clinical palpability and occurred more frequently in patients with optic neuropathy. Severe apical crowding was the most sensitive indication of optic neuropathy at CT. PMID- 2243968 TI - Rhabdomyosarcomas in the head and neck: MR imaging evaluation. AB - To determine the typical magnetic resonance (MR) signal intensity characteristics of rhabdomyosarcomas, short repetition time (TR)/short echo time (TE) (T1 weighted) and long TR (proton density and T2-weighted) images of 13 patients with rhabdomyosarcomas of the head and neck were retrospectively reviewed. Seven patients received gadopentetate dimeglumine injections. The most common MR appearance was that of a homogeneous mass, hyperintense to both muscle and fat on long TR/long TE images and isointense or minimally hyperintense to muscle on short TR/short TE images. All lesions of the patients who received gadopentetate dimeglumine enhanced markedly. Two lesions had intratumoral hemorrhage, and six were markedly heterogeneous in signal intensity. Similar MR signal intensity patterns have been described for lymphomas and nasopharyngeal carcinomas. The forte of MR imaging lies in its ability to delineate precisely the extent of the rhabdomyosarcoma. PMID- 2243969 TI - Epiphora: treatment by means of dacryocystoplasty with balloon dilation of the nasolacrimal drainage apparatus. AB - A new interventional radiologic procedure was developed for treatment of epiphora. A small-bore, soft-tipped guide wire was introduced through the superior canaliculus and guided under fluoroscopic control through the nasolacrimal drainage system for retrieval through the nasal aperture. A small bore angioplasty catheter was then introduced in a retrograde direction into the nasolacrimal drainage apparatus and dilated under fluoroscopic control. The procedure was attempted in 18 eyes of 17 patients with moderate to severe epiphora and was technically completed in 16; 13 of these cases demonstrated improvement, with 11 patients showing complete resolution of symptoms. In the three patients whose epiphora did not improve, no worsening of symptoms occurred. These results are preliminary; follow-up ranged from 7 weeks to 6 months. The authors believe that this technique may hold promise in the treatment of epiphora and may obviate the use of more invasive procedures. PMID- 2243970 TI - Mucocele of the cystic duct remnant in eight liver transplant recipients: findings at cholangiography, CT, and US. AB - The case histories and radiologic studies of eight liver transplant recipients who developed a mucocele of the allograft cystic duct remnant were retrospectively evaluated. All patients had clinical and/or laboratory evidence of biliary obstruction or cholangitis from 2 weeks to 3.3 years following transplantation. Cholangiographic, ultrasound (US), and computed tomography (CT) images were available for review in eight, five, and four patients, respectively. Cholangiograms demonstrated an extrinsic mass compressing the common hepatic duct in seven of eight patients. US and CT showed fairly well- to well-defined round fluid collections adjacent to the common hepatic duct in three and two patients, respectively. The findings of this study suggest that the detection at cholangiography of an extrinsic mass compressing the common hepatic duct appears to be specific for a mucocele of the allograft cystic duct remnant. CT and US images may offer confirmatory evidence. PMID- 2243971 TI - Colorectal tumors: an in vitro study of high-resolution MR imaging. AB - To study the potential utility of magnetic resonance (MR) imaging in staging colorectal tumors, 15 resected colonic segments containing 17 elevated lesions were examined on a 1.5- or 1.9-T superconductive MR system. The whole intestinal wall was apparent as three or five layers on images obtained with a short repetition time (TR) and short echo time (TE) and as six or eight distinct layers, including the intestinal wall proper as well as an adherent mucus layer and an outer layer of pericolonic fat, on the long TR/TE images. In cases of colonic carcinoma, MR images correlated well with the pathologic findings, including the macroscopic growth pattern, depth of mural invasion, and the presence of foci of calcific tumor necrosis and pools of extracellular mucin (colloid). These features suggest that MR imaging may be valuable in the clinical evaluation of colorectal tumors. PMID- 2243972 TI - Colonic stenoses: use of oral barium when retrograde flow is completely obstructed on barium enema studies. AB - Forty patients with complete obstruction to retrograde barium flow on barium enema examinations, without clinical or radiographic evidence of obstruction, were studied further with orally administered barium in the same session. All patients had undergone aborted double-contrast barium enema studies and had received antispasmodics intramuscularly before the examination. The authors describe the technique, as well as the clinical and radiologic findings, that allows the safe ingestion of oral barium in patients with stenotic lesions of the colon. In all patients, oral barium passed through the small bowel and the stenotic site in an average of 148 minutes, with no complications. In seven patients, there were synchronous lesions in the colon and small bowel, and the findings were determined better with oral barium studies in 19 patients. If a barium enema study is done and retrograde passage of barium is obstructed by a lesion in the left side of the colon, additional diagnostic information can be obtained by giving the patients oral barium. This practice is safe if precise criteria are applied. PMID- 2243973 TI - Feasibility of digital teleradiology for imaging evaluation of patients with acute right upper quadrant abdominal pain. AB - To assess the utility of a commercially available digital teleradiology system in evaluating patients with acute pain in the right upper quadrant, hard-copy images from 100 examinations (50 hepatobiliary scintigrams and 50 sonograms of the right upper quadrant) were digitized, transmitted via standard telephone lines, and viewed remotely on a video monitor. Video and hard-copy interpretations were then compared for degree of concordance. For the scintigraphic studies, hard-copy and video images were equal in demonstrating gallbladder and bile duct activity. Video images failed to depict the presence of bowel activity in one case. Gallstones were depicted equally well on hard-copy and video sonographic images. The video interpreters overestimated the presence of abnormal hepatic parenchyma and overlooked one case of right hydronephrosis. The video interpretations of the scintigrams and sonograms showed an overall error rate of 4%, comparable to the rate obtained when radiographs are interpreted remotely with digital teleradiology systems. PMID- 2243974 TI - Pancreatic transplants: CT-guided biopsy. AB - With use of computed tomographic (CT) guidance, 10 biopsies of pancreatic allografts were performed in four patients to determine the cause of pancreatic dysfunction. All biopsies were performed with an 18-gauge biopsy needle and with use of a biopsy gun. On four occasions, simultaneous biopsies of the pancreatic head and tail were performed. In nine of the 10 biopsies, specimens obtained were adequate for diagnosis. In two of the four simultaneous procedures, important histologic differences were noted between specimens from the head and those from the tail of the allograft. No complications occurred. These findings demonstrate the ease, accuracy, and safety of CT-guided biopsies of pancreatic transplants with a biopsy gun. Simultaneous sampling of the pancreatic head and tail may provide important clinical information that may not be available when the usual cystoscopically guided biopsy of the pancreatic head is used. PMID- 2243975 TI - Extracorporeal cholecystolithotripsy without oral chemolitholysis. AB - One hundred thirty-six patients completed extracorporeal biliary lithotripsy (EBL) for symptomatic cholecystolithiasis. Sonographic evidence of complete clearance of all stone fragments was the only criterion for treatment success, which occurred in 32 of the 71 patients (45%) followed up for 24 weeks and in 36 of the 59 patients (61%) followed up for 52 weeks. The authors' protocol varied from protocols of other researchers primarily in that no adjuvant chemolitholysis was used. However, the number of treatment sessions and total number of shock waves (a maximum of 4,000 shock waves per treatment session, 12,000 shock waves in a patient demonstrating no significant fragmentation, and 20,000 shock waves in a patient whose stones responded well to fragmentation) was higher than those in other reports. The results of treatment and complication rates in this study are comparable with those at centers using both shock-wave lithotripsy and chemotherapy. The authors conclude that EBL is developing into an important alternative to surgery, which was obviated in all patients with complete clearance of fragments from the gallbladder. PMID- 2243976 TI - Acute splenic sequestration crisis in two adults with sickle cell disease: US, CT, and MR imaging findings. AB - Acute splenic sequestration crisis (ASSC) is a rare complication in adults with sickle cell disease that is diagnosed clinically by means of sudden splenic enlargement and a rapid fall in hematocrit. Two cases of ASSC in adults with heterozygous sickle cell disease (sickle cell-thalassemia and sickle cell hemoglobin C disease) were studied with use of duplex Doppler ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging. In both cases, US showed patency of the splenic vein and multiple hypoechoic lesions on the periphery of an enlarged spleen that were of low attenuation on CT scans and hyperintense on both T1- and T2-weighted MR images. These findings were believed to be suggestive of subacute hemorrhage. This was confirmed pathologically in one case and suggested in the other by the presence of a low-signal-intensity ring, probably hemosiderin, surrounding one of the lesions. Also, the remainder of the spleen in both patients was of normal signal intensity, unlike the diminished signal intensity seen in patients with homozygous sickle cell disease. Further study is needed to determine the role of imaging in the diagnosis and treatment of ASSC. PMID- 2243977 TI - Hepatic infarction in preeclampsia. AB - Two cases of hepatic infarction in toxemia of pregnancy are described. Both patients had associated laboratory findings of the HELLP syndrome (hemolytic anemia, elevated liver enzyme levels, and low platelet levels). Computed tomography (CT) showed nonenhancing low-attenuation areas varying in configuration from peripheral, well-defined, wedge-shaped lesions to larger abnormalities. Magnetic resonance imaging showed a corresponding area of low signal intensity on T1-weighted images with high signal intensity on T2-weighted images. Ultrasound showed several well-defined peripheral hypoechoic areas. The low attenuation and lack of enhancement on CT scans and the absence of mass effect are the key distinguishing features. PMID- 2243978 TI - Receptor imaging: application to MR imaging of liver cancer. AB - A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors. PMID- 2243979 TI - Persistent right umbilical vein: an ominous prenatal finding? AB - The persistence of a right umbilical vein is an uncommon finding, with only a dozen cases reported since 1826. The persistent right umbilical vein may replace the normal left umbilical vein or be supernumerary. The anomaly is associated with numerous and occasionally lethal malformations. In this series, only three of six fetuses (and another two in the literature) had no associated anomalies. All the others had a variety of associated lesions ranging from minor to lethal. The appearance at ultrasound is easy to recognize: The intrahepatic portion of the umbilical vein is lateral to the gallbladder, and the portal vein curves toward the stomach, instead of parallel to it. Since the recognition of the persistent right umbilical vein is simple and does not require additional scanning (it is visible in the section used to measure the abdominal perimeter), the author suggests using it as an indicator for more in-depth scanning. PMID- 2243980 TI - Vicarious contrast material excretion in patients with acute unilateral ureteral obstruction. AB - Radiographs of 45 patients with evidence of acute unilateral ureteral obstruction at intravenous urography, obtained at least 24 hours after injection of contrast material, were retrospectively studied. Vicarious contrast material excretion (VCME) as evidence by gallbladder opacification on delayed radiographs was seen in 19 patients (42%), 10 of whom also showed extravasation of contrast material. A total of 15 of the 45 patients developed spontaneous extravasation; 10 (67%) showed VCME, while only nine of the 30 patients (30%) who did not have spontaneous extravasation of contrast material showed VCME. The creatinine level was elevated (greater than 1.5 mg/dL [133 mumol/L]) in four patients with VCME and in six patients without. This series indicates that VCME is more common than previously appreciated in patients with acute unilateral ureteral obstruction and occurs with greater frequency when obstruction is associated with contrast material extravasation. PMID- 2243981 TI - In vivo human testicular function assessed with P-31 MR spectroscopy. AB - The clinical feasibility of assessing testicular metabolic integrity with phosphorus-31 magnetic resonance (MR) spectroscopy was investigated in six healthy volunteers and 23 patients with azoospermia. MR spectroscopic findings were compared with sperm count and motility in all patients and with findings at testicular biopsy in 23 patients. Significant differences (P less than .05) were found between the P-31 spectra of normal and azoospermic testicles in the following peak area ratios: phosphomonoester (PM)/beta-adenosine triphosphate, PM/phosphodiester, and inorganic phosphate/PM. In the patients with azoospermia, there were significant differences in these same peak area ratios between patients with primary testicular failure and those with chronic tubular obstruction. Although the differences between these two groups were statistically significant, there was a large overlap in numbers, and therefore a study with a larger patient population will be required. P-31 MR spectroscopy is a sensitive tool for assessment of testicular metabolic integrity and differentiation of normal testicles from those with markedly decreased spermatogenesis. PMID- 2243982 TI - Renal artery stenosis: evaluation with color Doppler flow imaging. AB - Renal artery stenosis (RAS) is the most common correctable cause of hypertension. The current study was undertaken to evaluate the usefulness of color Doppler flow imaging as a screening examination in the detection of significant RAS. Fifty five kidneys in 30 patients were examined with aortography and color Doppler flow imaging in a double-blind fashion. The peak systolic velocity (PSV) in the renal artery, the renal-aortic ratio (RAR) (ie, the ratio of the PSV in the renal artery to the PSV in the aorta), and the renal artery resistive index were determined and compared with the percentage of stenosis as determined with angiography. Ultrasound (US) criteria used to diagnose RAS were (a) an RAR of 3.5 or greater and/or (b) a renal artery PSV of greater than 100 cm/sec. Doppler tracings were obtained in 25 (69%) of 36 kidneys with a patent single renal artery. RAR and PSV each yielded a sensitivity of 0% in the diagnosis of RAS. Doppler tracings were obtained in three (50%) of six occluded renal arteries. Accessory arteries were present in 13 (24%) of 55 kidneys, but none were visualized with color Doppler flow imaging. The authors conclude that with current technical capability, color duplex US is not an adequate screening method for the detection of RAS. PMID- 2243983 TI - Intrauterine spermatic cord torsion in the newborn: sonographic and pathologic correlation. AB - In five newborn patients with spermatic cord torsion, sonography demonstrated an enlarged and globular testis, hydrocele, and skin thickening. In four of these patients the testicular parenchyma was heterogeneous. Peripheral hypoechoic areas were seen in two of the four patients; the other two had a central hypoechoic region and a peripheral echogenic rim. The testis in the fifth patient was diffusely hyperechoic. Duplex Doppler sonography performed in two patients failed to demonstrate any signal in the spermatic cord in either the abnormal or contralateral hemiscrotum. Scintigraphic findings were positive for testicular torsion in two patients and equivocal in three patients. Surgery was performed 2 12 days after sonography and established the diagnosis of spermatic cord torsion. Pathologic examination demonstrated hemorrhagic infarction of the entire testis as well as scattered calcifications. The authors conclude that a solid globular testicular mass seen during the neonatal period is suggestive of intrauterine spermatic cord torsion. PMID- 2243984 TI - Hypertrophic pyloric stenosis: volumetric measurement of nasogastric aspirate to determine the imaging modality. AB - The authors postulated that volumetric measurement of residual gastric aspirate in neonates and infants with nonbilious projectile vomiting could enable differentiation between patients with hypertrophic pyloric stenosis (HPS) and those with gastroesophageal reflux (GER) and help to determine whether ultrasound (US) or fluoroscopy of the upper gastrointestinal tract would best confirm the diagnosis. In the 38 patients (all but two of whom had been fasting for 3-4 hours), 10 mL or more of nasogastric aspirate was considered indicative of obstruction. HPS occurred in 91.7% of patients with 10 mL of aspirate or more, whereas GER occurred in 85.7% of patients with less than 10 mL. The differences between the two groups were statistically significant. Solely on the basis of residual volume (greater than or equal to 10 mL), the cause of vomiting could be differentiated, prior to standard radiologic studies, 89.4% of the time. It is concluded that patients with projectile vomiting who have 10 mL or more of residual aspirate in the stomach should undergo US for confirmation of HPS; those with less than 10 mL should undergo fluoroscopy for confirmation of GER. PMID- 2243985 TI - Association of vertebral end plate fracture with pediatric lumbar intervertebral disk herniation: value of CT and MR imaging. AB - A retrospective review of the radiologic findings in 31 patients less than 21 years old who underwent laminotomy for lumbar disk herniation revealed six cases of associated avulsion fracture of the vertebral end plate, a prevalence of 19%. All fractures were found in the 14-17-year-old subgroup (six of 19), a prevalence of 32%. In four patients, plain radiographs did not reveal the fracture. Computed tomographic (CT) findings were diagnostic in all six cases. Magnetic resonance (MR) images, obtained in three patients, demonstrated the avulsed cortical fragment and what are assumed to be the attached Sharpey fibers. On sagittal MR images, these structures had a configuration with the appearance of a "Y" or "7". Four of these six patients underwent bilateral laminotomies. The need for more extensive surgical resection may not be apparent at plain radiography or myelography but can be predicted with CT and MR imaging. PMID- 2243986 TI - Focal fibrocartilaginous dysplasia associated with tibia vara. AB - Focal fibrocartilaginous dysplasia of the tibia at the insertion of the pes anserinus (the expanded tendinous insertion of the gracilis, sartorius, and semitendinous muscles) is a rare unilateral lesion with a characteristic deformity of the proximal tibial metadiaphysis. It is associated with unilateral tibia vara in toddlers. Three cases of this entity are described, and the radiologic features are presented. Recognition of this disease is important because the response to conservative therapy is excellent. PMID- 2243987 TI - Myocardial tagging in polar coordinates with use of striped tags. AB - Regional deformation abnormalities in the heart wall provide a good indicator of ischemia. Myocardial tagging with magnetic resonance imaging is a new method of assessing heart wall motion during contraction. Current methods of myocardial tagging either do not provide two-dimensional information or lack a coordinate system well adapted to the morphology of the heart. In this article, the authors describe a new tagging method that provides a true polar coordinate system, with both radial and angular dimensions. This is accomplished with use of a section selective version of spatially modulated magnetization resulting in striped tags (STAGs). These STAG planes are placed in the myocardium in a star pattern so that they intersect on the long axis of the heart and stripes appear through the width of the heart wall. In the short-axis view during contraction, rotation around the long axis yields angular information such as shear and twist, while separation of the stripes within the myocardium permits measurement of radial thickening. Therefore, this method provides a coordinate system for calculating two dimensional strain that is adapted to the morphology of the left ventricle. PMID- 2243988 TI - Determination of left ventricular volume and mass with use of biphasic spin-echo MR imaging: comparison with cine MR. AB - In this study, the authors compared a new rapid spin-echo magnetic resonance (MR) imaging method, biphasic MR, with cine MR in the determination of left ventricular volume and mass in healthy volunteers. Biphasic spin-echo MR images covering the entire heart were obtained with use of the electrocardiogram R wave and the downslope of the T wave at both end diastole and end systole, respectively. Biphasic MR-determined values correlated well with small standard errors of the estimate (end-diastolic volume = 7.82 cm3, end-diastolic mass = 10.20 g, end-systolic mass = 10.08 g, ejection fraction = 2.62%) and were more reproducible. Cine MR-defined end-systolic volume was significantly larger (P less than .01) and ejection fraction was significantly smaller (P less than .005) than biphasic MR-determined values probably because of the uncertainty in isolating end systole with cine MR. Left ventricular volumes, mass, and ejection fraction are more accurately and reproducibly quantified in a more time-efficient manner with use of biphasic MR than with cine MR because of its significantly shorter image acquisition and reconstruction times. PMID- 2243989 TI - Penetrating aortic ulcers: diagnosis with MR imaging. AB - The authors studied seven patients with penetrating aortic ulcers with use of magnetic resonance (MR) imaging. All patients were evaluated for acute chest symptoms, and the presence of aortic ulcers was confirmed by means of angiography in all seven patients. Five patients also underwent computed tomography (CT). Three patients underwent surgical repair of the thoracic aorta. MR findings included intramural hematoma and focal aortic wall ulceration in four patients, focal ulceration in one, focal intramural hematoma in one, and focal intramural hematoma with rupture in one. The diagnosis of intramural hematoma was made by the detection of increased signal intensity on T1- and T2-weighted MR images. MR imaging was superior to angiography in depicting the extent of intramural thrombus, although one ulceration diagnosed at angiography was missed at MR imaging. MR imaging was superior to CT in differentiating acute intramural hematoma from atherosclerotic plaque and chronic intraluminal thrombus, although it did not depict displaced intimal calcification in one patient with extensive intramural hematoma. PMID- 2243990 TI - Inferior vena caval filter thrombi: evaluation with intravascular US. AB - A 20-MHz intravascular ultrasound (US) transducer inside a percutaneously inserted catheter was used to evaluate inferior vena caval (IVC) filters for thrombi in vitro and in vivo. Six different IVC filters were studied with intravascular US in a saline-filled model. Each filter had a characteristic, recognizable US pattern. Experimental thrombi as small as 0.5 cm3 were easily detected. Intravascular US was used clinically 25 times to evaluate the IVC in 23 patients with 24 IVC filters. Positive-contrast cavograms were available for comparison in all 25 cases. In 13 cases, no thrombi were identified in the filter or IVC with either intravascular US or cavography; in five of 12 cases with thrombi, intravascular US and cavography demonstrated the thrombi equally well. In six cases, intravascular US was superior to cavography in detection or delineation of thrombus in the IVC or filter. Intravascular US was considered superior to external duplex US in evaluation of caval thrombi in all 21 cases available for comparison. No complications from intravascular US were noted. PMID- 2243991 TI - Obstructive jaundice: use of expandable metal endoprosthesis for biliary drainage. Work in progress. AB - Expandable metal endoprostheses were implanted transhepatically in 61 patients with obstructive jaundice. Fifty-three patients had malignant and eight had benign obstructions. Because of the small diameter of the compressed stent (7 F), primary implantation of the stent without a previous catheter drainage was preferred. Postprocedural complications occurred in three patients (5%) (biliary pleuritis, peritonitis, hepatic artery aneurysm). The 30-day mortality rate was 8.2%. Reocclusions were observed in six of the patients with malignant obstructions (11%) (observation period, 1-10 months; mean, 4.5 months) and in two of the patients with benign stenoses (25%) (observation period, 3-21 months; mean, 9 months). The higher reocclusion rate of benign obstructions must be interpreted with care because of the small number of patients. From their preliminary experience, the authors conclude that expandable metal endoprostheses offer patency rates equal to those of plastic stents. The implantation trauma is reduced due to the small 7-F introducing catheter system. PMID- 2243992 TI - Iliac artery stenosis and occlusion: preliminary results of treatment with Gianturco expandable metallic stents. AB - Ten patients with atherosclerotic stenosis or occlusion of the iliac artery were treated with Gianturco expandable metallic stents. In the five cases of stenosis, only balloon dilation was performed prior to placement of stents. The five patients with occluded arteries were given intraarterial infusions of urokinase before balloon dilation and stent placement. Clinical symptoms improved in all patients, and no technical failures or complications occurred. Doppler ankle brachial index studies were performed in nine cases, and in all nine cases the indexes improved after stent placement. During follow-up of 2-18 months (mean, 10.3 months), all arteries remained patent. Follow-up angiograms showed slight intimal thickening and no restenosis. Long-term follow-up and more clinical experience will be necessary to evaluate the efficacy of this stent. However, preliminary results suggest that the Gianturco expandable metallic stent is of value in the treatment of arterial occlusive disease. PMID- 2243993 TI - Invasive papillary carcinoma of the breast: mammographic appearance. AB - The mammographic findings in 18 patients with invasive papillary carcinoma were studied retrospectively. The mammograms of 10 patients showed a multinodular pattern, and seven patients had solitary nodules. One patient had an irregular, ill-defined mass in the retroareolar region. Two patients were found to have carcinoma in the contralateral breast, and two patients had intraductal carcinoma adjacent to the invasive papillary carcinoma. The varied mammographic features that may occur with this rare breast malignancy are discussed. PMID- 2243994 TI - Radiation doses due to breast imaging in Manitoba: 1978-1988. AB - The number of mammographic examinations performed annually in the province of Manitoba, Canada, and their associated radiation doses (total collective breast dose and average glandular dose [AGD] per view) are reported for the period 1978 1988. These data indicate that the total number of examinations performed annually increased by a factor of five during the 11-year study. The total annual collective breast dose, meanwhile, increased at a much slower rate, from 40 person-Gy in 1978 to 97 person-Gy in 1988; this difference is attributable to the gradual replacement of xeroradiography by screen-film mammography and to changes in technique. In the late 1980s, the AGD due to xeroradiography for a craniocaudal view was 3.3 mGy, a factor of 2.4 greater than the corresponding dose associated with dedicated screen-film units. PMID- 2243995 TI - Rotator cuff lesions: signal patterns at MR imaging. AB - The signal intensity patterns of rotator cuff lesions at magnetic resonance (MR) imaging were evaluated in 80 patients who had surgical correlation and in 13 asymptomatic individuals (14 shoulders). Six cadaver shoulders were examined with MR, and histologic correlation was obtained in four. All studies were performed at 1.5 T with a flexible circular surface coil. The accuracy of MR imaging in detection of full-thickness cuff tears (31 patients) was 0.95 and of partial thickness tears (16 patients), 0.84. The most common and accurate pattern for full-thickness cuff tears (22 of 31 tears) was a region of intense signal seen on T2-weighted images. Less often the torn region consisted of an extremely degenerated and attenuated tendon with moderate signal intensity or was obscured by low-signal-intensity scar. The intense signal pattern on T2-weighted images was also accurate, although a less common finding (seven of 16 cases), in the diagnosis of partial tears. Tendinitis was recognized as focal or diffuse regions of increased signal intensity or a nonhomogeneous pattern of increased signal often associated with tendinous enlargement. In some patients, manifestations of subacromial-subdeltoid bursitis was present. Tendon degeneration was also manifested as regions of increased signal intensity. Some similarity and overlap of signal patterns of partial interstitial tears, tendinitis, and tendon degeneration are observed. PMID- 2243996 TI - Neuromuscular diseases: evaluation with high-frequency sonography. AB - Forty-four patients with clinically suspected neuromuscular disease and 12 healthy volunteers underwent high-frequency ultrasound examination of the rectus femoris, vastus medialis, vastus lateralis, and biceps brachii muscles, and the number of perimysial septa was determined. These numbers and muscle/soft-tissue ratios of the lower extremity were compared. Findings were correlated with results of muscle biopsy in all patients with suspected disease. Using the number of perimysial septa in the lower extremity, the authors found significant differences between the muscles of healthy volunteers and those of patients with Duchenne muscular dystrophies, other muscular dystrophies, and spinal muscular atrophies: The receiver operating characteristic curve showed that an average of 12 perimysial septa within 1 cm of muscle is the ideal cutoff value to differentiate subjects without morphologic changes from those with pathologic findings. The authors conclude that this measurement is useful for differentiation of neuromuscular diseases and may be a noninvasive, reproducible means with which to evaluate disease progression. PMID- 2243997 TI - Cystic rheumatoid arthritis: description of a nonerosive form. AB - In a study of patients with rheumatoid arthritis (RA), 9% (n = 70) were found to have a cystic form. At radiologic examination of these patients with cystic RA, the first abnormality seen consisted of periarticular intraosseous cysts without erosions. The cysts were distributed symmetrically, most often located at the proximal side of the joints and predominantly around the proximal interphalangeal, metacarpophalangeal, and wrist joints of the hands and the first interphalangeal and metatarsophalangeal joints of the feet. Computed tomographic scans showed the peripheral intraosseous location of the cysts. Magnetic resonance images showed that the cysts may contain fluid, inflamed synovia, or both. Cysts can be an important feature in the diagnosis of RA and a supplement to the criteria of the American Rheumatism Association. Osteoporosis, joint-space narrowing, and joint destruction occurred less frequently in patients with cystic RA than in patients with classic RA. Of the patients with cystic RA, 54% were male, and 50% were seronegative. This study is a supplement to and an enlargement on earlier descriptions of cyst predominance in RA. PMID- 2243998 TI - Widespread inflammatory response to osteoblastoma: the flare phenomenon. AB - A case of vertebral osteoblastoma caused a diffuse, reactive inflammatory infiltrate in two vertebrae, adjacent ribs, and the paraspinous soft tissues. The authors call this the flare phenomenon. On magnetic resonance images the diffuse inflammatory response caused a misleading appearance that simulated a malignant process (lymphoma or Ewing sarcoma). A computed tomographic myelogram was diagnostic. PMID- 2243999 TI - Small nodular lesions in the lung periphery: new approach to diagnosis with CT. AB - To evaluate relationships between lesions in the lung periphery and surrounding structures, particularly vessels and bronchi, axial multiplanar reconstruction (AMPR) computed tomography (CT) was used to study 26 patients who underwent surgical resection of pulmonary nodules less than 3 cm in diameter. Findings at AMPR CT, conventional CT, and digital radiographic tomography were compared with findings obtained at evaluation of the resected specimen with regard to the ability to display the relationships between vessels, bronchi, and lesions. AMPR CT was significantly superior to conventional CT and digital radiographic tomography in detecting involvement of pulmonary vessels (P less than .001). Involvement of pulmonary veins was seen in all lung cancers, whereas such involvement was seen in only one of eight nonneoplastic lesions. Thus, involvement of pulmonary veins is strongly suggestive of malignancy. AMPR CT permits three-dimensional visualization and morphologic assessment of pulmonary nodules. PMID- 2244000 TI - Search and nonsearch protocols for radiographic consultation. AB - Six radiologists, acting as radiograph reviewers, used two different consultation protocols to differentiate among 292 ambiguous chest radiographic findings: 120 simulated nodules and 172 normal findings (previous readers' false-positive reports of nodules). The nonsearch protocol identified each finding (by film location), and reviewers rated the likelihood of each finding's being a pulmonary nodule. The search protocol asked reviewers to report and rate all locations regarded as possible nodules on each radiograph and assigned a default negative rating to any unreported finding (nodule or normal structure). Receiver operating characteristic analyses demonstrated a significantly higher accuracy for each reviewer's search-protocol discriminations between these nodules and ambiguous normal findings. This superiority-of-search result suggests that radiologists' second opinions about suspected lesions might be more accurate when consultants follow a search protocol, independently reviewing radiographs without prior knowledge of the specific findings that concerned the primary radiograph readers. PMID- 2244001 TI - Potential usefulness of an artificial neural network for differential diagnosis of interstitial lung diseases: pilot study. AB - An artificial neural network approach was applied to the differential diagnosis of interstitial lung diseases. The neural network was designed to distinguish between nine types of interstitial lung diseases on the basis of 20 items of clinical and radiographic information. A data base for training and testing the neural network was created with 10 hypothetical cases for each of the nine diseases. The performance of the neural network was evaluated by means of receiver operating characteristic analysis. The decision performance of the neural network was high; it was comparable to that of chest radiologists and superior to that of senior radiology residents. The preliminary results strongly suggest that the neural network approach has potential utility in the computer aided differential diagnosis of interstitial lung diseases. PMID- 2244002 TI - Pulmonary masses: contrast enhancement. AB - Radiographic studies to discriminate benign from malignant pulmonary masses have previously focused on the morphologic and, more recently, the computed tomographic (CT) attenuation characteristics of the lung mass. Experience with the use of an intravenously administered iodinated contrast medium in examining the enhancement properties of lung masses was reviewed. Distinctive differences in the vascularity, pathophysiologic features, and pharmacodynamics of malignant versus benign pulmonary masses were identified. Forty-five patients with peripheral pulmonary masses were examined. Enhancement was evaluated by means of optical density values measured on trispiral tomograms of the lung masses before and after bolus injection of contrast medium. Results suggest that contrast enhancement of pulmonary masses can be measured on sectional images and that this may become a feasible diagnostic method in the detection of lung cancer. CT offers a simplified technique that is now being explored by the authors. PMID- 2244003 TI - Scatter fractions in AMBER imaging. AB - Images of two phantoms were obtained with use of an advanced multiple-beam equalization radiography system, and scatter fractions were estimated with use of a photostimulable phosphor imaging system. Scatter fractions in the equalized images were lower in the mediastinum-equivalent areas and higher in the lung equivalent areas, relative to images that were conventionally acquired with use of an antiscatter grid. The differences are attributed to a reduction in incident exposure in the lungs and the presence of cross-scatter between lung and mediastinal regions. PMID- 2244004 TI - Simple technique for shaping hydrophilically coated guide wires: usefulness in selective angiography. AB - A method is described to shape hydrophilically coated guide wires with specially prepared electronic round-nose pliers. These shaped wires can be engaged with 4-F catheters in the performance of selective angiography. Now even demanding selective catheterizations may be accomplished more easily and safely with small catheters. PMID- 2244005 TI - Metallic ballistic fragments: MR imaging safety and artifacts. PMID- 2244006 TI - Fetal omphalocele: prenatal US detection of concurrent anomalies and other predictors of outcome. PMID- 2244007 TI - Guided fine-needle aspiration biopsy of nonpalpable breast lesions: calculation of accuracy values. PMID- 2244008 TI - Human immunodeficiency virus infection and neurologic dysfunction. PMID- 2244009 TI - Secretory antibody response to viral vaccines. PMID- 2244010 TI - Human T lymphotropic virus type I neurotropism. PMID- 2244011 TI - Hepatitis B surface antigen expressed in murine cells. PMID- 2244012 TI - [Atopic dermatitis: the role of mechanical trauma]. AB - A case of atopic dermatitis was observed in a patient in whom clinical observation and radioimmunoassays failed to demonstrate any possible role of allergic mechanisms. The lesions were caused exclusively by contact with the irritating substances and mechanical pressure, even, at times, by pressure of clothes. PMID- 2244013 TI - [Bacterial flora in the urethra of men with Chlamydia trachomatis urethritis before and after treatment with ofloxacin]. AB - From urethra of 40 men with CTU, 190 bacterial strains were isolated, 110 before and 80 after treatment with OFX (400 mg daily for 5 days). Among the strains coexisting with Chlamydia trachomatis, Staphylococcus epidermidis (30.9%), Micrococcus (13.6%), Streptococcus group D (10.9%) and Staphylococcus aureus (10.9%) were isolated more frequently than others. The in vitro susceptibility testing showed that, in comparison to erythromycin, doxycycline, oxytetracycline and co-trimoxazole, OFX was the most active antimicrobial agent against the majority of bacteria (except streptococci) isolated from urethra in CTU cases in men. The OFX treatment was found to reduce the total number of isolated strains, including Staphylococcus aureus and Staphylococcus saprophyticus, without disturbing normal urethral flora. PMID- 2244015 TI - [Social perception of AIDS risk]. AB - An all-Polish study was carried out of a representative sample of 1402 adult subjects for establishing the level of social knowledge of AIDS, the character of attitudes, the consequences of informative activities etc. The AIDS threat was considered by the responders as low, with subjects with rather more loose sexual life fearing infection relatively less. It may be supposed that this was due to a greater experience with infections, better knowledge and lower threat awareness. The lack of threat awareness of the society seems to be determined in an equal degree by the low knowledge of AIDS and relatively small number of cases in this country. This limited knowledge of AIDS may lead to a more rapid spread of the disease, and, consequently, to panic reactions, intolerance and aggression against patients and risk groups. This could be prevented only by appropriate health education. PMID- 2244014 TI - [Rapid spread of HIV infections among narcotic addicts]. AB - In the Institute of Venereology, 5351 patients (75.1% of males, 24.9% females), intravenous drug users (IVDU), have been tested for the presence of HIV antibodies in the period from Jan 1986 to Dec 31 1989. They were patients of detoxication wards and/or pensioners of drug treatment centers. HIV antibodies were determined by the EIA method (Abbott Recombinant HIV-1 EIA test), and positive results were confirmed by the western-blot technique. HIV antibodies were found in 292 patients: 228 males (78.1%) and 64 females (21.9%), which accounts for 5.5% of tested IVDU. In 1986-1987 all tests were negative, although the first HIV infection was confirmed in 1985 in homosexual group. The first positive HIV test in drug addicts was detected in Aug 1988 after testing of 2254 patients. In 1989 276 sera were positive for HIV antibodies (11.2%) among 2471 patients studied. Our study indicates that HIV infection is spreading rapidly in IVDU population. Infections of drug addicts with HIV represent 66% of total detected cases of HIV antibody-positive individuals in Poland; among 30 diagnosed AIDS cases 5 were drug users. PMID- 2244016 TI - The effects of single dose oral hydralazine on blood flow through human lung tumours. AB - Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients. PMID- 2244017 TI - The effects of oral hydralazine on blood pressure, cardiac output and peripheral resistance with respect to dose, age and acetylator status. AB - Cardiovascular responses are reported in 21 patients with carcinoma of the bronchus taking part in a study of tumour perfusion. There were eight slow and 12 fast acetylators; acetylator status was not determined in one patient with a history of sulphonamide allergy. Hydralazine dose ranged from 25 to 150 mg orally (equivalent to 0.37 to 2.86 mg/kg). Mean arterial blood pressure fell from 98 mmHg before hydralazine to 90 mmHg 60 min after hydralazine (p = 0.002) and mean cardiac output rose from 5.53 l/min to 7.75 l/min (p = 0.00005). Calculated total peripheral resistance fell by 30% (p = 0.0002). Falls in peripheral resistance per milligram hydralazine administered were greater in patients over 70 years of age. Acetylator status was a poor predictor of response. Side-effects were reported by eight patients and were related to the magnitude of fall in peripheral resistance (p = 0.0005) but not to falls in blood pressure (p = 0.12). PMID- 2244018 TI - Dose-volume correlation in radiation-related late small-bowel complications: a clinical study. AB - The effects of the volume of irradiated small bowel on late small-bowel tolerance was studied, taking into account the equivalent total dose and type of pre irradiation surgical procedure. A method was developed to estimate small-bowel volumes in the high-dose region of the radiation treatment using CT-scans in the treatment position. Using this method small-bowel volumes were measured for three field and AP-PA pelvic treatments (165 cm3 and 400 cm3, respectively), extended AP-PA pelvic treatment (790 cm3), AP-PA treatment of para-aortic nodes (550 cm3) and AP-PA treatment of para-aortic and iliac nodes (1000 cm3). In a retrospective study of 111 patients irradiated after surgery for rectal or recto-sigmoid cancer to a dose of 45-50 Gy in 5 weeks, extended AP-PA pelvic treatment (n = 27) resulted in a high incidence of severe small-bowel complications (37%), whereas for limited (three-field) pelvic treatment (n = 84) the complication rate was 6%. These complication data together with data from the literature on postoperative radiation-related small-bowel complications were analysed using the maximum likelihood method to fit the data to the logistic form of the dose-response relation, taking the volume effect into account by a power law. The analysis indicated that the incidence of radiation-related small-bowel complications was higher after rectal surgery than after other types of surgery, which might be explained by the development of more adhesions. For both types of surgery a volume exponent of the power-law of 0.26 +/- 0.05 was established. This means that if the small-bowel volume is increased by a factor of 2, the total dose has to be reduced by 17% for the same incidence of small-bowel complications. PMID- 2244019 TI - The importance of vocal cord mobility in T2 laryngeal cancer. AB - In a retrospective study 75 patients with T2 laryngeal cancer treated from 1981 through 1985 were analysed. Of this group 71 patients had a full course of radiotherapy as primary therapy. All 71 patients were given 70 Gy/7 weeks on the primary and 50 Gy/5 weeks on the neck, 2 Gy per fraction. Various prognostic factors for local control and survival were studied. In our patient group we found vocal cord mobility to be an important prognostic factor for ultimate local control and survival. Patients with impaired cord mobility had a significantly worse ultimate local control (76%) than patients with normal cord mobility (98%) and a significantly worse corrected actuarial survival. It is concluded that impaired cord mobility means more advanced disease. Future studies will have to answer the question how to improve the local control rate in patients with impaired cord mobility, for example, by incorporating laryngectomy earlier in the treatment program of those patients who can not be cured by radiotherapy alone or by using innovative radiotherapy protocols. PMID- 2244020 TI - The Dijon clinical staging system for early rectal carcinomas amenable to intracavitary treatment techniques. AB - The Dijon clinical and endoscopic staging system for intracavitary radiotherapy of rectal cancer takes into account the size and the depth of penetration of the rectal wall. Its prognostic value was evaluated in a series of 72 patients with rectal adenocarcinoma treated at the Centre de Lutte Contre le Cancer G. F. Leclerc in Dijon: 30 presented with a clinical stage (CS) T1A (purely exophytic tumors of less than 3 cm). The 5-year local relapse-free actuarial survival (LRFS) was 97%. Fourteen patients with CS T1B (infiltrative component and less than 3 cm diameter) had a LRFS of 77%. Nine patients with CS T2A tumors (with larger exophytic tumors) has a LRFS of 65%. Nineteen CS T2B cases (larger than 3 cm with an infiltrative component) presented a LRFS of 60%. The size of the tumor and the clinical estimate of the infiltration of the rectal wall both have a significant prognostic value: adenocarcinoma of less than 3 cm (n = 44) had a LRFS of 93% versus 59% in larger ones (n = 39; p = less than 0.01). Free mobile lesions (n = 39) did better (n = 33; LRFS = 86%) than infiltrated tumors (n = 33; LRFS = 66%; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244021 TI - Radiosensitivity testing of primary cervical carcinoma: evaluation of intra- and inter-tumour heterogeneity. AB - Biopsies from 89 patients with cervical carcinoma were studied using a clonogenic assay to obtain values for the surviving fraction at 2 Gy (SF2). Heterogeneity in intrinsic radiosensitivity was investigated by independently processing multiple biopsies from 18 tumors. No significant differences between intra-tumour SF2 values were demonstrated (p = 0.30). The results have shown that intra-tumour heterogeneity is not a limitation to radiosensitivity testing using the Courtenay Mills assay. A wide range of values (0.13-0.97) for SF2 was obtained with a mean value of 0.47 +/- 0.18 (+/- 1 S.D., CV = 38%) for 52 squamous cell carcinomas and 0.59 +/- 0.27 for four adenocarcinomas. There were statistically significant differences between the individual tumours (p less than 0.001). From the analysis of-variance of all the SF2 results it appears to be the surviving fractions below about 0.40 and those above about 0.7 which show significant differences in radiosensitivity between pairs of tumours (p = 0.05). Also 36% of the values of SF2 show significant differences from the mean SF2 of all tumours. The storage of tumour cell suspensions in liquid nitrogen improved the colony-forming efficiency (CFE) but it did not alter the radiosensitivity. PMID- 2244022 TI - Melphalan resistant human ovarian tumour cells are cross-resistant to photons, but not to high LET neutrons. AB - High linear energy transfer (LET) fast neutrons for the local control of advanced head and neck tumours are currently being evaluated at several centres. Fast neutrons are believed to produce more direct, and less OH mediated damage than photons, and consequently be less affected by intracellular thiol levels. Chemoresistant tumours with elevated thiol levels may therefore be more effectively controlled by fast neutron therapy than by photons. The "in vitro" radiation response of melphalan sensitive and resistant human ovarian tumour cell lines has demonstrated that melphalan resistance confers a 1.5-fold level of cross-resistance to photons, primarily attributable to a 2-fold decrease in the alpha component in the resistant OAW42/MER cell line. Pretreatment of the melphalan-resistant line with the thiol depleting agent buthionine sulphoximine (BSO) restored the magnitude of alpha to a value similar to that in the chemosensitive cell line. The survival curves of these cell lines following neutron irradiation were near exponential, with similar values of alpha. This study has demonstrated that melphalan resistant tumour cells are cross-resistant to photon irradiation, but not to fast neutrons. The mechanism of cross resistance has yet to be determined, but glutathione (GSH) appears to be involved. PMID- 2244023 TI - Vocal cord cancer: 2B worse than not 2B? PMID- 2244024 TI - [Bone radiology in the pages of "La Radiologia Medica". Review of the papers published throughout the 75 years of life of the journal]. PMID- 2244025 TI - [Magnetic resonance of the bone marrow]. AB - Magnetic resonance imaging has opened new possibilities to current diagnostic radiology in the evaluation of bone marrow. In the past, bone marrow imaging was based on conventional radiology, nuclear medicine and computed tomography; they all exhibited some capabilities but also some limitations. Bone image on MR scans is due to bone marrow, with its different components of red and yellow marrow. Since red marrow is mostly liquid and yellow marrow contains large amounts of fat, the signal will vary, on T1-weighted images, according to their different proportions. There is a gradual change from red marrow to yellow marrow from birth to adulthood: this change determines the MR appearance of bone marrow, the different features of which should be known for a correct evaluation of pathologic findings. MRI is extremely effective in the evaluation of infiltrative disorders of bone marrow, such as leukemia, lymphoma, myeloma, primary and metastatic skeletal tumors, and infections. MRI allows depletive disorders of bone marrow and ischemic processes to be studied. Finally, MRI allows the non invasive follow up of bone marrow pathologic conditions, thus representing a valid alternative to biopsy. PMID- 2244026 TI - [Magnetic resonance angiography of the neck vessels: imaging optimization]. AB - The neck vessels of 60 patients were studied by means of magnetic resonance angiography, with gradient-echo FISP sequences with short TR and TE and with a 25 degrees flip angle. To study arterial neck vessels, sequences were acquired on the coronal and on the sagittal planes, centered on the cricoid. The intracranial tract of the vertebral arteries required axial sequences centered under the floor of the sella turcica. Post-processing was obtained with the maximum intensity projection technique. The coronal and sagittal sequences were rotated on the axial plane from 0 degrees to 180 degrees with 15 degrees interval, while axial sequences were rotated on the sagittal plane from 0 degrees to 180 degrees with the same interval. TR, TE and flip angle values were very important for image quality: the thinner the volumes the more effective resolution power and vessel visualization. These volumes should not exceed 1.5 mm. Axial rotations of coronal sequences from -45 degrees to +45 degrees and of sagittal sequences from 60 degrees to 120 degrees were useful for diagnosis. The intracranial tract of the vertebral arteries was clearly depicted after axial sequences and after 75 degrees and 135 degrees sagittal rotations. PMID- 2244027 TI - [Magnetic resonance angiography of the pulmonary artery. Preliminary considerations]. AB - The possibility was evaluated of imaging the pulmonary artery with MR angiography. Twenty healthy volunteers were studied using 3D FT gradient-echo sequences on the coronal plane, with post-processing by the maximum intensity projection method. TE and TR remaining short, flip angles were selected to increase pulmonary artery signal in contrast with hypointense adjacent tissues and vessels. Flip angle selection allowed the optimal differentiation between pulmonary artery and aorta with 15 degree-25 degree angles (range: 110.7 to 122 for the 15 degree flip angle and 158.7 to 182.1 for the 20 degree flip angle). The sequence was obtained on the coronal plane and the following parameters were employed: TR 0.03 s, TE 10 ms, flip angle 15 degree-20 degree, slice of the total volume 100 mm with 64 partitions, 256 x 256 matrix, 1 zoom factor, 1 acquisition. The patient was positioned with the right hemithorax raised by 30 degrees to visualize the common pulmonary artery and lying on his back, face upward, to visualize the right and left pulmonary arteries. Post-processing employed axial plane rotations from -45 degrees to +45 degrees, with 5 degrees step, and from 0 degrees to 180 degrees, with 15 degrees step. Angio-MR images of the pulmonary artery allowed the visualization of its main components, up to its right and left lobar branches. The main limitation of this technique consisted in its poor spatial resolution. PMID- 2244029 TI - [Fibrous dysplasia of the facial bones. A CT study]. AB - The authors report 7 cases of fibrous dysplasia of the facial bones which were evaluated with CT. The involvement of the facial bones by fibrous dysplasia is an uncommon event, which causes different syndromes according to the extent of bone invasion. In all the cases occurred to our observation CT allowed an exact spatial evaluation of the dysplasia, and therefore a correct surgical planning. Moreover, CT densitometric values and CT appearance of fibrous dysplasia often suggested the correct diagnosis. PMID- 2244028 TI - [Quantitative analysis of bone density in multiple myeloma]. AB - Bone lesions are the main sign of neoplastic proliferation of multiple myeloma (MM), a disseminated malignant disease which originates in, invades and replaces normal bone marrow. The most characteristic radiographic pattern is a focal lytic lesion, well-defined or "punched-out", generally with no surrounding bone reaction. The association is confirmed between MM and osteoporosis, as reduced bone density (osteopenia) and pathologic fractures (ribs, spine). This paper is aimed at evaluating the importance of osteopenia in both diagnosis and prognosis of MM. Eighteen patients affected with MM were examined with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DEXA) for bone densitometry in lumbar spine and proximal femur. The patients (12 males and 6 females) were classified according to Durie's clinical criteria and to the radiographic patterns suggested by Merlini. The results indicate the patients with an advanced clinical stage (III) and scintigraphic expansion of bone marrow to have low densitometric values on both QCT and DEXA. There was substantial agreement between the 2 methods, but DEXA had a higher number of false positives. Instrumental diagnostic protocol may be thus planned as follows: 1) conventional radiography; 2) bone marrow scintigraphy; 3) bone densitometry of lumbar spine, with QCT. The patient is then to be followed with conventional and/or digital radiography in symptomatic locations, and with bone scintigraphy. PMID- 2244030 TI - [Echo-guided biopsy in peripheral pulmonary lesions. Our experience]. AB - Twenty-nine patients with peripheral intrathoracic lesions underwent real-time US and US-guided biopsy. The lesions were mainly atypical fluid collections in 3 patients and mainly solid in the extant 26. Biopsies performed with fine aspirating or cutting needles (20-22 gauge) were successful in all patients; an unquestionable diagnosis was made in 27 cases with cytology and/or histology. Only one patient experienced mild asymptomatic pneumothorax after biopsy, which did not require chest-tube drainage. The authors stress the important diagnostic role of US-guided fine-needle biopsy as an useful and safe method for the evaluation of peripheral intrathoracic lesions. PMID- 2244031 TI - [CT in the staging of neoplasms of the gallbladder]. AB - The authors report the results of 50 cases of gallbladder carcinoma studied by means of CT, which were observed since 1984. Twenty-five cases were confirmed at surgery and 25 were selected among those in which CT, clinical history, natural disease evolution and matching with other instrumental and laboratory examinations were highly suggestive of gallbladder carcinoma. The high incidence is reported of such CT signs, which may be considered typical, as the presence of soft tissue in gallbladder area (92%), liver infiltration (78%), and the presence of metastatic lymph nodes (36%); they may or may not be associated to less specific signs. CT appears as the most reliable examination for both diagnosis and staging of the disease. Unfortunately, due to the wide range of aspecific clinical signs, diagnosis is in most cases late and the disease has therefore a fatal outcome. PMID- 2244032 TI - [Ultrasonic study of the dimensions of the common bile duct in various postures]. AB - To date, the importance of patient position has not been considered in defining the normal range of the internal diameter of the main bile duct. The authors examined 160 patients to verify if significant changes in the internal diameter of the main bile duct take place when changing patient position. In 20/160 cases (12.5%) internal diameter was observed to decrease by greater than 1 mm, in 6/160 cases (3.75%) by greater than 2 mm. These changes were found more often in cholecystectomized patients and were mostly associated with an increase in the max absolute caliber of the main bile duct. Therefore, postural changes (dorsal decubitus, left lateral decubitus, upright position) of the patient are important factors when calculating max internal diameter of the main bile duct. Moreover, postural changes may play an analogous role to functional tests. PMID- 2244033 TI - [Diagnosis of deep venous thrombosis of the legs: accuracy of ultrasonography using vein compression]. AB - We prospectively compared real-time US findings with venographic results in the legs of 171 consecutive outpatients with clinically suspected deep venous thrombosis (DVT). In each leg the common femoral and the popliteal veins were evaluated with venography and US. The two examinations were independently performed and reviewed. Vein compressibility (VC), intraluminal echogenicity and response to Valsalva maneuver were evaluated with US. Venography detected DVT in 54/171 legs. 10/54 legs had isolated distal DVT. With VC, US was 100% specific, 87% sensitive and 96% accurate. 6/7 false negative US studies were due to isolated distal DVT; therefore US sensitivity for proximal DVT was 98%. The other two US diagnostic criteria were much less accurate than VC. VC-US is an accurate, cheap and reproducible test for the detection of DVT in symptomatic outpatients. PMID- 2244034 TI - [Ultrasonography in the diagnosis of deep venous thrombosis of the legs]. AB - One hundred consecutive inpatients with clinically suspected deep venous thrombosis (DVT) were examined by US; the last 19 cases were studied also by means of color-Doppler US. In order to evaluate the method reliability, US results were compared with those obtained with contrast venography, which was performed on all patients. The studied region included the femoro-popliteal vein, while no attempt was made to image the calf veins, which are difficult to evaluate with US. In our series, venographic results were in substantial agreement with US findings, with 99% and 100% sensitivity and specificity, respectively. Diagnosis was based only on noncompressibility of the thrombotic vein, despite the absence of visible clots; pulsed Doppler information supported diagnosis by evaluating blood flow. Further diagnostic progress was provided by color-Doppler US, which allows flow lumen to be defined in color. US also allowed the detection of the conditions mimicking DVT, such as muscular ruptures, hematomas, popliteal cysts, or compressive tumors. In conclusion, US and color Doppler US prove to be valid alternatives to contrast venography in the diagnosis of proximal DVT of the lower limbs. PMID- 2244035 TI - [Evaluation of the role of mammography and echography in breast diseases in a controlled caseload]. AB - Data concerning patients who underwent mammography and breast ultrasonography and then breast surgery were collected and analyzed with a computer archive system. In previous papers the authors reported both design and implementation of the computer archive and analyzed the results concerning uncontrolled collected data; in the present paper data concerning controlled cases are evaluated, distinguishing between symptomatic and asymptomatic cases. Asymptomatic patients represented 92% of the whole evaluated population. However only one third of the patients who underwent surgery for breast cancer was included in this group. Breast cancer was discovered in 65% of the patients who underwent diagnostic procedures and then surgery because of a palpable nodule. This percentage was lower (52%) in asymptomatic patients. Mammographic accuracy was about 90% in symptomatic patients and 81% in asymptomatic patients. Breast ultrasonography was performed as a subsequent step and always detected the lesion when palpable. Its sensitivity was 86% in asymptomatic patients. In patients who underwent surgery the false positive rate for cancer was higher with ultrasonography (59%) than with mammography (45%). Focal dysplasis were responsible for the majority of false positive diagnoses with both procedures. However, the false positive rate is low referring to the whole investigated population and is reshuffled by guided bioptic procedures. Ultrasonography was a useful tool when mammography had limitations: in fact ultrasonography detected a focal lesion in all patients with a surgically proven cancer and a previous negative mammography. The sets of data available from the continuous updating of the computer archive immediately clarified the differences between symptomatic and asymptomatic patients and stressed the diagnostic capabilities of the different procedures. PMID- 2244036 TI - [Transrectal echography and simultaneous uroflowmetry in the study of male urination. Considerations on 254 consecutive cases]. AB - The authors report on a series of 254 consecutive male patients who underwent transrectal US, sometimes combined with uroflowmetry, for the study of micturitonal phase. 170 patients were studied with both techniques. In 118 patients, there was complete agreement between the two methods about presence and degree of flow obstruction; partial disagreement was observed in 48 patients and complete disagreement in 4. On 44/52 patients with partial/complete disagreement diagnostic cystouretrography was performed. Our results demonstrate high agreement between the two techniques, except in case of micturition deficit with columnar hypertrophic bladder and in obstructive pathologic conditions of anterior urethra. PMID- 2244037 TI - [Lymph node metastasis of carcinoma of the cervix uteri. Role of lymphography and computerized tomography]. AB - The presence of lymph nodal metastases in the patients affected with carcinoma of the uterine cervix is of the utmost clinical relevance. In the Radiology, Obstetrics and Gynecology Departments of Pavia University we have evaluated the accuracy of lymphangiography and CT in recognizing lymph nodal metastases in 95 patients, 58 of them evaluated preoperatively (49 subsequently submitted to radical hysterectomy). CT accuracy was also evaluated in 37 patients with a clinically suspected relapse of cervical cancer. In the first group the overall results were: 91% accuracy, 88% sensitivity, 92.5% specificity for lymphangiography and 87.9% accuracy, 72.2% sensitivity, and 95% specificity for CT (in 49 patients, stage I-II, submitted to lymphadenectomy, lymphangiographic accuracy was 91%, sensitivity was 88%, specificity 92% versus CT accuracy 85.7%, 44.4% sensitivity, and 95% specificity). In the second group (relapse) CT accuracy, sensitivity and specificity were 94%, 100%, and 91%, respectively. In conclusion, lymphangiography gives better results than CT in the patients with early stages (I-II) of the disease. In advanced stages and relapses CT was found to have high accuracy in demonstrating lymph node status. This information is useful for treatment planning and for avoiding unnecessary surgical exploration. PMID- 2244038 TI - [Percutaneous transhepatic bilioplasty: long-term results]. AB - We report the results of a long-term follow-up of 40/101 patients with benign biliary strictures treated with percutaneous balloon dilatation (PBD) at the Radiology Department of the University of Turin, from March 1983 to March 1990. We excluded all the patients who were not followed or treated after June 1988, being their follow-up shorter than 18 months. All patients underwent accurate clinical, biological (AST, ALT, gammaGT, alcaline phosphatase) and US controls. Mean follow-up was 33.5 months. Mean success rate was 75% in strictures of bilioenteric anastomosis, 86% in iatrogenic strictures of the common bile duct, 65% in sclerosing cholangitis, 80% in papillary strictures in which endoscopic treatment had not been possible for anatomical reasons. Our results, compared to the most important radiological and surgical series, show PBD to have lower morbidity than surgery and no mortality during the so-called peroperative period (30 days). Moreover, in case of recurrences, PBD can be repeated without further complications and does not affect eventual surgery. PMID- 2244039 TI - [Radiotherapy of carcinoma of the nasopharynx. Results and analysis of prognostic factors]. AB - Radiation therapy of the patients with nasopharyngeal carcinoma results in permanent loco-regional control in 55-100% of cases according to stage of disease. Five-year overall survival rates range 30-55% and 5-year disease-free survival 30-40%. Factors affecting survival are: sex, age, overall patient conditions, Epstein-Barr associated antibodies, histology, T and N stages, cranial nerve and neck nodes involvement, staging method, dose and fractionation of radiation therapy, and adjuvant treatment. Our results in 94 patients can be summarized as follows: 78.4% local control, 89.8% control of lymph nodes clinically palpable at diagnosis, 40% overall 5-year survival, and 38% 5-year disease-free survival. Significant prognostic factors in our series of patients were T and N stages and histology. PMID- 2244040 TI - [Radiotherapy in the treatment of tumors of the nasopharynx in advanced stage]. AB - This series consists of 25 patients affected with nasopharyngeal carcinoma in an advanced stage (T3-T4) treated at the Radiation Oncology department of the Institute of Radiology, University "La Sapienza", Rome, from 1978 through 1988. The patients were irradiated with X-rays produced by a LinAc with 4 MeV energy, for a total dose of 60/75 Gy on tumor and 50/60 Gy on nodes. In 7 cases radiation therapy was combined with chemotherapy. Actuarial survival at 60 months was 47%; patients with T3 cancer treated with a total tumor dose over 65 Gy showed a significant statistical increase of survival. Adjuvant chemotherapy did not produce statistically significant increase of survival. Radiation therapy was the treatment of choice in nasopharyngeal carcinoma in an advanced stage, whereas the role of chemotherapy remains questionable, even though a bad prognosis requires aggressive and combined treatment. PMID- 2244041 TI - [Post-radiotherapy complications in malignant tumors of the nasopharynx. Analysis of 141 cases]. AB - This study was aimed at retrospectively analyzing the incidence and severity of the complications occurred in 141 patients affected with nasopharyngeal carcinomas treated with exclusive radiotherapy from 1960 to 1986. The acute complications were analyzed (85/141 grade II-III mucositis which generally came to a complete remission) which occurred during and immediately after radiation treatment. The late damage was then studied which occurred in 74/141 patients (52.5%) and which may worsen patients' quality of life. Finally, the incidence and severity of damage were correlated with some parameters: sex, age, performance status, risk factors (tabagism, alcoholism, diabetes), stage, total dose, fractionation, and processing techniques for treatment planning. PMID- 2244042 TI - [Multimodal treatment of locally advanced carcinoma of the breast. Experience at the Galliera di Genova Hospital]. AB - All patients with locally advanced breast cancer receiving definitive irradiation (with or without surgery) at the Radiation Oncology Service, Ospedali Galliera, Genova, Italy, from 1969 through 1986, were retrospectively reviewed. Group A consisted of 187 patients, affected with stage III disease, who received radiation therapy after radical surgery. Irradiation of the chest wall and regional lymph node chains was accomplished with divergent tangential beams of Cobalt: the dose was calculated at the mid-plane of the tangential field separation and was 50Gy (2 Gy/day, 5 fractions/week), followed by additional 10 15 Gy boost to the scar. One hundred and five patients received combined hormonotherapy and/or chemotherapy. After a mean follow-up of 49+ months we observed 21 local recurrences (16 in metastatic patients); 64 patients developed only distant metastases. Actuarial survival at 5 years is 55%. Group B consisted of 36 inoperable patients who received definitive irradiation. Radiation therapy planning was very similar to that in group A, even though after 50 Gy the breast and the tumor area were boosted with restricted fields up to a total dose of 80 90 Gy. Fifteen patients received combined hormonotherapy and/or chemotherapy. At the end of the treatment overall response rate was 89%; actuarial survival at 5 years is 38%. Toxicity was generally mild and no death related to the treatment was observed. Our retrospective analysis confirms the importance of a multimodal approach to locally advanced breast cancer in order to free most patients from disease and to produce excellent local control, even though more randomized studies are necessary to improve the long-term survival of these patients. PMID- 2244043 TI - [Intraoperative radiotherapy using electrons. Applicable software]. PMID- 2244045 TI - [Responsibility of the radiologist regarding the use of the equipment for radiologic diagnosis]. PMID- 2244044 TI - [New medico-nuclear applications in the postoperative study of kidney transplant]. AB - Isotope nephrography is nowadays widely applied to the study of renal transplants. Major advantages of this technique have been obtained for the prognostic evaluation of transplant rejection and in the differential diagnosis of oliguria and anuria. The authors report on 14 cases of renal transplant recipients examined with renal scintigraphy 3-4 days after surgery. In agreement with literature data, the authors wish to stress the importance of the correct use of different tracers (DTPA, MAG3) for renal scintigraphy and nephrography. Problems and complications in renal transplants are studied with the simultaneous use of these tracers. The evaluation of renal blood flow and vascular complications requires radiopharmaceutical DTPA, which is excreted only by glomerular filtration. In contrast to 99mTc-DTPA, 99mTc-MAG3 is now the tracer of choice in the evaluation of tubular function. Some problems are still to be solved regarding patients management, such as the necessary chronologic relationship between surgical phases and nephrographic/scintigraphic examinations and early and late follow-up of renal transplant recipients. PMID- 2244046 TI - [Radiologic deontology in daily practice]. AB - The rapid and far-reaching technological evolution that has taken place in diagnostic imaging has deeply changed the radiologist's role, increasing his professional liability. He is in fact responsible for the materials and the equipment employed, for the choice of the examination necessary to solve the clinical problems, for the proper execution of the test, for the validity of the iconographic documentation, for the correct diagnostic interpretation and final report. Whenever the instrumental research involves actual risks of damage (not only potential) it is up to the radiologist to inform the patient to obtain the consent for the execution of the test. PMID- 2244047 TI - [The radiologist and mammography]. PMID- 2244048 TI - [Gynecologic brachytherapy with high dose intensity]. PMID- 2244049 TI - [Interstitial brachytherapy in pelvic neoplasms]. PMID- 2244050 TI - [Pulmonary psittacosis. Presentation of a small intrafamilial epidemic]. PMID- 2244051 TI - [Post-radiotherapy occlusion of the right pulmonary artery. Description of a case]. PMID- 2244052 TI - [Percutaneous treatment of splenic arterio-venous fistula. Description of a case]. PMID- 2244053 TI - [Search of abdominal foreign bodies in drug traffickers. Radiography and echography]. PMID- 2244054 TI - [Renal echography in the early diagnosis of malignant hemolymphopathy in children. Apropos of 4 cases]. PMID- 2244055 TI - [Experimental models in arthrosis]. PMID- 2244056 TI - [Addison's disease: a clinico-epidemiologic study of 45 cases]. AB - We present the clinical-epidemiological results obtained in a series of 45 patients diagnosed of Addison disease between 1967 and 1988. The incidence was 0.83 cases/100,000 inhabitants/year and the prevalence was 10 cases/100,000 inhabitants. The etiology was unknown in 44.4% of cases tuberculous in 24.4% and in 31.1% of cases the caused could not be established with the classical clinical and radiological criteria. Amongst the studied variables in each etiological group, we highlight the association with other autoimmune processes and the development of extraadrenal tuberculous infection after Addison disease diagnosis. We discuss the approach to etiological diagnosis and the convenience of tuberculostatic treatment in EAT cases. PMID- 2244057 TI - [Visceral leishmaniasis in Alicante. Analysis of 21 cases]. AB - We present 21 cases of visceral Leishmaniasis diagnosed in our hospital during the past 8 years. The diagnostic method used was the visualization of the parasite in bone marrow aspiratory puncture. All cases presented fever at admission, hepatosplenomegaly, anemia elevated sedimentation rate and polyclonal gammapathy. Two of our patients were diagnosed of AIDS during the course of the disease. Cure was observed in all cases after one cycle treatment with pentavalent antimonials except for the two AIDS cases one of whom died due to cerebral toxoplasmosis. We point out visceral Leishmaniasis as an opportunistic infection in patients with AIDS and its resistance to the usual treatment. PMID- 2244058 TI - [Prevalence, forms of clinical presentation and treatment of arterial hypertension at an emergency unit]. AB - In order to determine the prevalence of arterial hypertension and clinical presentation of the hypertensive crisis, as well as the need and efficacy of treatment, 3626 patients who were seen at an Emergency care Unit during a period of 37 randomly chosen days in a total time period of three months, have been studied. Two hundred and fifty one patients presented arterial hypertension, defined as a systolic arterial pressure above 160 mmHg and/or diastolic above 95 mmHG, which represents 6,92% of medical emergencies and 1.79% of total emergencies. Only 104 patients (2.86%) seeked help for some pathology related to hypertension, of whom 49 (19.5% of hypertense patients) presented as a hypertensive emergency, being the acute lung edema and unstable angina the most frequently encountered emergencies. Nifedipine was the most frequently used drug in both groups and managed to control pressure levels in almost 90% of patients with a hypertensive emergency in a mean time of less than one hour. PMID- 2244059 TI - [Erection while walking and stenosis of the lumbar canal]. AB - Lumbar channel stenosis is frequently manifested by a Cauda Equina intermittent claudication. Only exceptionally erections during walking have been described. We have observed two patients with severe lumbar channel stenosis and a Cauda Equina syndrome with intermittent erections during walking. One patient was laminectomized presenting a clinical improvement. There does not exist a satisfactory explanation for this strange affectation. PMID- 2244060 TI - [Gastroenteritis with eosinophilia caused by Giardia lamblia]. AB - A case of gastroenteritis due to Giardia lamblia with severe dehydration and complicated with arterial thrombosis, accompanied by eosinophilia and increased serum IgE levels, is presented. The relationship between Giardia and eosinophilia and allergic manifestations is discussed as well as its pathogenesis. PMID- 2244061 TI - [2 new cases of Y-autosome translocation associated with azoospermia]. AB - We present two new cases of Y-autosome translocation which were detected in two azoospermic males. In the first case the translocation was de novo with the karyotype: 46,XY,t(Y;16)(q12;q11-12). In the second case the karyotype was: 46,XY,t(Y;1)(cen-q11;cen-p11), t(Y;15)(q12;p11), the mother having been a carrier of the same Y-15 translocation, and showing the chromosomic formula: 46,XX,t(Y;15)(q12;p11). PMID- 2244062 TI - [Experimental osteoarthritis and its course when treated with S-adenosyl-L methionine]. AB - Degenerative arthropathy was experimentally induced in the right knee of 24 rabbits. The animals were randomly divided in 3 groups of 8 rabbits each. S Adenosyl-L-Methionine (SAMe) was administered intramuscularly to 2 groups. One group received 30 and 60 mg/kg/day i.m. The remaining group was a control and received only a diluent. After 12 weeks of therapy rabbits were sacrificed and tibial and femoral cartilage specimens of both knees were taken. The latter was stained with hematoxylin -eosine, Masson's trichromic and Safranine 0 stains and was microscopically studied. The thickness and cell density of the lesioned cartilages were significantly greater in both groups treated with SAMe than the group control (p less than 0.001). Statistical differences (p less than 0.05) were found within 60 and 30 mg/kg/day of SAMe. A greater concentration of proteoglycans in the cartilage matrix was found in animals treated were as, a severe reduction was found in controls. The severity of the lesions, based on the histologic-histochemical analysis, was significantly lower in rabbits receiving SAMe (p less than 0.0005). These differences were correlated with the administration of SAMe and the possible mechanisms of action are discussed. PMID- 2244063 TI - [Multiple pathology in abdominal CAT]. PMID- 2244064 TI - [Familial Mediterranean fever. The metaraminol test as a cause of severe cephalalgia]. PMID- 2244065 TI - [Monotherapy using cefotaxime (Claforan) in severe dysentery caused by highly resistant Shigella]. PMID- 2244066 TI - [Akathisia, a diagnosis to keep in mind]. PMID- 2244067 TI - [Urticarial vasculitis. Response to treatment with colchicine]. PMID- 2244068 TI - [Graves-Basedow's disease and systemic lupus erythematosus]. PMID- 2244069 TI - [Hyperbilirubinemia and sepsis caused by S. aureus]. PMID- 2244070 TI - [Visceral leishmaniasis in patients infected with HIV in the Barcelona area]. PMID- 2244071 TI - [Long-term prognosis of cryptogenetic hemoptysis]. PMID- 2244072 TI - [Functional pathology. Intracapsular temporomandibular dysfunction]. AB - Intracapsular dysfunction of the TMJ is analyzed, based on the concepts of dysfunctional and functional pathology, including a diagnostic clasification this is analyzed under a etiopathogenic point of view, clinical characteristics, different types of cases named disco-condilar disorders. PMID- 2244073 TI - [Glass ionomer, current clinical indications in restorative dentistry]. AB - The glass ionomer cements are a relatively new class of dental materials used for a variety of purposes, including cavity lining, restorations, cementation of casting, crown building and pit and fissure sealant. They offer two great advantages over most other materials release of fluoride and adhesion to dentin and enamel. Glass ionomer is very susceptible to dehydration and hydration, especially during the first 15 min and lesser extent the remaining 24 hours. Therefore, the use of rubber dam and a water proof varnish is critical to prevent loss of hardness and translucency. PMID- 2244074 TI - [Advances in dentistry]. AB - After a long period of research, a lot of elements of high technology have come to dentistry. Intraoral camaras, magnetic resonance imaging devices, digital radiographic equipment, laser, and computer systems that custom, mill and place restorations. The future evolution of all these devices, could be spectacular, considering its numerous possibilities in dental field. PMID- 2244075 TI - What statistics should we teach medical undergraduates and graduates? AB - It is suggested that the emphasis on teaching statistics to medical undergraduates has usually been quite wrong: that the courses have become much too long, too detailed, and irrelevant to the needs of the majority. Examples are given which may help to introduce the basic concepts which all medical (and dental) undergraduates require, and which form a basis for the more traditional teaching of analytical methods to the appropriate subset who proceed to undertake medical research. PMID- 2244076 TI - Who should teach medical statistics, when, how and where should it be taught? AB - As far as we can tell, there is no single answer to any of these questions. This paper describes some of the approaches adopted in the teaching of medical statistics in the U.K. medical schools. It is suggested that collaboration between non-statistically qualified teachers and medical statisticians is beneficial, with an emphasis in the application of statistical principles to interesting and 'relevant' medical topics. A block of 'laboratory based' teaching in the early years may be followed by occasional, clinically focused sessions later in the undergraduate course. Research oriented courses, made available when postgraduates have a real and pressing need for information, are thought likely to be most valuable and rewarding for students and statisticians. It is thought that the use of information technology to improve the communication of concepts and 'facts' during lectures, and for ad hoc enquiries by students, is likely to make the most of the limited teaching resources. The future is thought to be in the greater use of small group or individualized teaching which confirms or tests the knowledge gained from students use of I.T. supported activities. Unless lecturers collaborate in evaluative studies which compare different teaching methods, it will never be possible to provide valid generalizable advice to teachers of medical statistics. PMID- 2244077 TI - Evaluation of statistics teaching given to medical undergraduates. AB - Medical undergraduates in all United Kingdom medical schools receive statistics teaching, but attempts to establish the efficacy of this teaching have been scanty. Establishment of clear educational objectives is a prerequisite to meaningful evaluation. Most medical schools have attempted to obtain feedback from their students by administering questionnaires. Examination performance can provide very pertinent information if a finely detailed marking scheme is developed, identifying issues that are generally poorly grasped. Controlled trials may be carried out within an institution but encounter problems of contamination and low power. It should eventually be possible to develop multi institutional evaluation methods. PMID- 2244078 TI - How we should approach the future. AB - There is little doubt that there are still major problems with the statistical aspects of published medical research. This paper argues that it is not sufficient to teach statistics to medical undergraduates, when the bulk of their courses are being taught by the very same individuals who continue to undertake and publish substandard research. Instead, any undergraduate teaching needs to advance in parallel with courses given to the clinical staff within medical schools. PMID- 2244079 TI - Statistics for medical students in the 1990's: how should we approach the future? AB - Medical statistics teaching in the U.K. has moved over the past twenty years from needing justification to acceptability. In the future teachers need to involve statistical and medical colleagues to improve the content and presentation of their material. While some techniques must continue to be taught, the conceptual aspects of scientific evaluation and assessment will need to increase. PMID- 2244080 TI - Statistical interim monitoring of the Cardiac Arrhythmia Suppression Trial. AB - The Cardiac Arrythmia Suppression Trial was stopped much earlier than planned. Statistical considerations played a very important role in the decision. Flexible group sequential testing was developed for the trial by implementing a Lan and DeMets procedure with use of the permutation test. We compute P-values from the joint permutation distribution of the test statistics, so we do not need to estimate the sampling distribution which in general is rather difficult to do without strict assumptions. The method also gives an exact test for small samples and allows us to use more complicated or non-Gaussian statistics. We also utilized stochastic curtailment ideas to evaluate various scenarios that might occur during the course of the trial, which assisted the Data and Safety Monitoring Board in making appropriate decisions. PMID- 2244081 TI - Practical Bayesian analysis of a simple logistic regression: predicting corneal transplants. AB - The Bayesian analysis of a logistic regression model is described using an example of predicting the need for a corneal transplant in keratoconus. Controversy over the use of subjective prior information in Bayesian methods is avoided by a formulation representing negligible prior information. Simple computational procedures are described, and it is argued that the results are more accurate, clearer and make fuller use of the information contained in the data. Analysis of more complex models is considered. In particular, it is argued that classical methods as implemented in the computer package GLIM can be used as approximations to Bayesian methods, particularly at the initial stage of model selection. PMID- 2244082 TI - Measuring interrater reliability among multiple raters: an example of methods for nominal data. AB - This paper reviews and critiques various approaches to the measurement of reliability among multiple raters in the case of nominal data. We consider measurement of the overall reliability of a group of raters (using kappa-like statistics) as well as the reliability of individual raters with respect to a group. We introduce modifications of previously published estimators appropriate for measurement of reliability in the case of stratified sampling frames and we interpret these measures in view of standard errors computed using the jackknife. Analyses of a set of 48 anaesthesia case histories in which 42 anaesthesiologists independently rated the appropriateness of care on a nominal scale serve as an example. PMID- 2244083 TI - A method for the evaluation of dose-toxicity relationships in clinical trials. PMID- 2244084 TI - [Computer-assisted bibliographic searches. A means of continuing education]. PMID- 2244085 TI - [Access to databanks: TRANSNET, a service example]. PMID- 2244086 TI - [Cardiological card index]. PMID- 2244087 TI - [Practical epidemiology: functional disorders and magnesium deficiency]. PMID- 2244088 TI - [Computers as an aid in diagnosis. Acute abdominal pains]. PMID- 2244089 TI - [Computerized medical records of the practitioner: usefulness and feasibility]. PMID- 2244090 TI - [Communication among physicians]. PMID- 2244091 TI - [The medical record]. PMID- 2244092 TI - [Practical observations apropos of an occurrence in private practice: the medical follow-up of a hospitalized patient]. PMID- 2244093 TI - [The computer in a health system]. PMID- 2244094 TI - [Medical informatics: faster, more efficient, more productive: can one dream?]. PMID- 2244095 TI - [Cortisone and rheumatism. Abuse and adverse effects]. PMID- 2244096 TI - [Micro-crystalline arthropathies: what is new?]. PMID- 2244097 TI - [Rheumatological manifestations of Lyme disease in Switzerland]. PMID- 2244098 TI - [Alcoholism: various current questions]. PMID- 2244099 TI - [Tryptophan and eosinophilia (II)]. PMID- 2244100 TI - [Helicobacter pylori, peptic diseases and colloid bismuth]. PMID- 2244101 TI - [Current status, perspectives and limitations of serotonin precursors]. PMID- 2244102 TI - [Crico-arytenoid articulation and sequelae of intubation. General principles of phoniatric rehabilitation]. PMID- 2244103 TI - [Creativity: a psychiatrist's viewpoint]. PMID- 2244104 TI - [What is the place of lithotripsy in the treatment of gallbladder calculi?]. PMID- 2244105 TI - [Laboratory results in clinical procedures]. PMID- 2244106 TI - [Chronic fatigue syndrome, fibromyalgia and depression]. PMID- 2244107 TI - [Evaluation of dental continuing education, 1989]. PMID- 2244108 TI - [Who will study dentistry. What attracts students to dentistry]. PMID- 2244109 TI - [Metal allergies in dental practice]. PMID- 2244110 TI - [Masseter muscle reflex]. PMID- 2244111 TI - [Capitation--dental payment--experience in USA and Great Britain]. PMID- 2244112 TI - [Facial trauma as a result of work-related accidents]. PMID- 2244113 TI - [Transplantation of premolar into position of an anterior traumatized tooth]. PMID- 2244114 TI - [Nelly: dialysis is my life. Interview by Christian Moreau]. PMID- 2244115 TI - [Poland at the end of the tunnel]. PMID- 2244116 TI - [Intolerable intolerances]. PMID- 2244117 TI - [Proper role. Impossible mission]. PMID- 2244118 TI - [Dental-maxillary dysmorphism]. PMID- 2244119 TI - [Non-surgical treatment of biliary lithiasis]. PMID- 2244120 TI - [Acute leukemias in children: prognostic factors]. PMID- 2244121 TI - [Leukemia I: the acute leukemias]. PMID- 2244122 TI - [Anti-AIDS JETBAC system]. PMID- 2244123 TI - [Facets of the period after cancer]. PMID- 2244124 TI - [Josee Thill: living with the elderly. Interview by Christian Moreau]. PMID- 2244125 TI - [Theater of insanity]. PMID- 2244126 TI - [Still students ... already health educators]. PMID- 2244128 TI - [Maintenance of indwelling central venous catheters]. PMID- 2244127 TI - [Luxembourg: old problems, new solutions]. PMID- 2244129 TI - [Suffering of caregivers in geriatrics]. PMID- 2244130 TI - [Ototoxicity of the aminoglycosides]. PMID- 2244131 TI - [Aortic insufficiency]. PMID- 2244132 TI - [Antivitamin K: a new mode of expression for surveillance of treatments, the international normalized ratio]. PMID- 2244133 TI - [Diabetes in the older patient]. PMID- 2244134 TI - [CRIPS (regional center of information and prevention of AIDS]. PMID- 2244135 TI - [J.P. Contis speaks of the CGOS (committee of administration of social work in public hospitals)]. PMID- 2244136 TI - [Interview with Gerard Vincent, director of hospitals.. Interview by O. Burrus, N. Wehrlin]. PMID- 2244137 TI - [Emergency care. School health]. PMID- 2244139 TI - [Are we corporate beings?]. PMID- 2244138 TI - [AIDS: departmental programs]. PMID- 2244140 TI - [Between scanners and "seancers"]. PMID- 2244141 TI - [To be an immigrant and growing old]. PMID- 2244142 TI - [Prescriptions and reconciled executions]. PMID- 2244143 TI - [Safer sex]. PMID- 2244144 TI - [A peasant in slippers]. PMID- 2244146 TI - [The "Yuppie" disease]. PMID- 2244145 TI - [Stop non-professionalism]. PMID- 2244147 TI - [Thoracic drainage]. PMID- 2244148 TI - [Leukemia II: treatments associated with chronic leukemias]. PMID- 2244149 TI - [Meningococcal infection prevention]. PMID- 2244150 TI - [The nursing profession in France. Extramural services in prison administration and legal protection of youth]. PMID- 2244151 TI - [Admission, screening for and prevention of AIDS]. PMID- 2244152 TI - [A "bad nurse". Interview by Christian Moreau]. PMID- 2244153 TI - [Leaving for the Third World ... and after?]. PMID- 2244154 TI - [Care of vertebro-medullary injuries]. PMID- 2244155 TI - [Silence is worse than death]. PMID- 2244156 TI - [Managing the death of a child: the expected death]. PMID- 2244157 TI - [Children, HIV and vaccination]. PMID- 2244158 TI - [Managing the death of a child: the sudden death]. PMID- 2244159 TI - [The "replacement" child]. PMID- 2244160 TI - [Amputation: unnecessary grief in children]. PMID- 2244161 TI - [SUMPPS: (University services for preventive medicine and promotion of health) the fullness of health]. PMID- 2244162 TI - [An easier autumn]. PMID- 2244163 TI - Spontaneously metastasizing variants of a human lung carcinoma cell line: monoclonal antibody characterization. AB - Spontaneously occurring microscopic lung and lymph node metastases (in athymic mice) of a low metastatic human lung carcinoma cell line, UCP3, and its high metastatic variant, MV522, were isolated. Characterization of the variants included karyotypic and isoenzyme analyses; assessment of spontaneous metastatic capabilities in athymic mice, and monoclonal antibody analyses. The high metastatic variant LNT had barely detectable amounts of a glycoprotein molecule with apparent Mr 73 kd and 90 kd, which was present in the other cell lines. This molecule was detected in 20/24 primary human neoplasms but only in 3/18 metastatic neoplasms, suggesting a loss during the metastatic disease process. PMID- 2244165 TI - "Empowerment" issues will top nursing's agenda over the next decade. PMID- 2244164 TI - Pay equity: accurate job descriptions can empower nurses. PMID- 2244166 TI - [Nitrates in vegetables--proposals for their limitation in Poland]. AB - Maximal permissible amounts of nitrates in vegetables and potatoes in Poland are proposed. These food products were divided into four groups according to their ability of accumulation of these substances. Moreover, a group of vegetables from special raising plots was isolated, they would be used for feeding small children, patients, and elderly subjects which would have a declared higher health quality. PMID- 2244167 TI - [Nutritive value of daily food rations prepared in various regions of the country. I. Energy value and the levels of proteins and fats]. AB - The diets were prepared in laboratory on the basis of analysis of family budgets carried out by the Central Statistical Bureau in 1986. In the study two socioeconomic groups were considered: that is workers in industry and mental workers with medium incomes. For the preparation diets about 70 food products were obtained from retail sales in 1988. The diets were prepared for live regions of the normal recommended intake diets of energy and protein was realized in these diets in about 90%, and the requirements for fat were covered in 104% in the diets of workers and 114% in the diets of non-workers. The degree of realization of the recommended intake was similar to the results obtained in intake diets in 1973 and 1981, but lower than that in 1980. No diets related to the region of the country. PMID- 2244168 TI - [Vitamin C levels in fresh, frozen and canned broad beans in relation to their varieties and degree of maturity]. AB - The content of vitamin C was investigated in seeds of broad been, the cultivars Windsor Bialy, Comprimo RS, Green Hangdown, and Threefoldwhite, harvested, frozen or canned with the content of dry matter at the level of 30%. Moreover, in cultivars Comprimo RS and Threefoldwhite the vitamin C was determined as depending on seed maturity within 25-40% of dry matter at 5% intervals. The compared broad bean cultivars, frozen or canned at the level of 30% d.w. in seeds differed by the vitamin C content. The extreme differences reached 21% for the raw material, 32% for frozen seeds cooked, and 15% for canned appertized seeds. However, the ranking of cultivars in the final products differed from that in the raw material. The vitamin C content decreased with increasing degrees of seed ripeness in the range from 25-40%. This particularly concerns fresh seeds of Threefoldwhite cv. In the final products differences were smaller and reached 2 6% in cooked frozen seeds and 18-24% in appertized canned seeds. Blanching decreased the vitamin C content by 14-43%. Freezing of blanched seeds and the 6 month storage of frozen goods decreased this content by about 24-56%. Frozen whole seeds contained 9.3-13.8 mg of vitamin C in 100 g after cooking (compared with fresh seeds, the losses reached 56-73%) and appertized canned seeds 8.2-11.7 mg in 100 g (compared with fresh seeds, the losses reached 63-73%). The average difference in favour of cooked frozen seeds reached 17%. The difference in vitamin C content between whole seeds and cotyledones varied within 1-9%. PMID- 2244169 TI - [Selenium in human environment]. AB - Selenium belongs to the group of elements which may be regarded as useful only in a very narrow range, while in excess doses they exert a harmful action. The content of the element in soil is usually from 0.1 to 2 mg/kg, with the Scandinavian soils have a low level of selenium, not exceeding 0.3 mg/kg. The highest level, exceeding 3000 mg/kg was noted in Northern Ireland. Selenium content in soil over 500 mg/kg produces chronic selenium intoxication in domestic animals. Selenium accumulation by plants is a selective process and depends on the chemical state of the element in soil and pH of soil. It is considered that the daily requirement for selenium is 50-300 mcg for adults, while the toxic dose is regarded as 5 mg daily. The toxic effects of selenium in the environment include inflammatory processes of the extremities in herbivorous animals (the so called Degnal disease in India and the Alkali disease in Great Britain). Selenium deficiency in the environment leads to the so called white muscle disease in these animals in Great Britain. Selenium is considered also to protect the organism in case of poisoning with lead, mercury or cadmium. PMID- 2244170 TI - [Evaluation of cadmium, mercury and lead intake with daily food rations]. AB - Using the data of the Central Statistical Bureau concerning the consumption of about 90 basic food products daily food rations were reproduced as taken by medium-income worker families. The diets were reproduced in Lublin, Olsztyn, Poznan, Warsaw and Wroclaw determining in them cadmium, mercury and lead by atomic absorption spectrophometry. It was found that weekly intake of cadmium with food rations was in the range from 133 to 189 mcg, that of lead was 504 to 952 mcg, and mercury from 61.6 to 154.0 mcg. The obtained results were not exceeding 50% PTWI for any of these metals but they were rather higher than those in previous years, which indicates increasing contamination of food products with toxic elements. In areas with higher industrialization level the dietary intake of metals was as a rule higher than in areas with lower accumulation of industry. PMID- 2244171 TI - Building materials and risk of leukemia. AB - Using information data obtained from 958 patients with leukemia and the same number of healthy controls matched for sex, age and place of residence the relative risk of leukemia was calculated in relation to the character of the material from which the building was built where the patients and controls were living. The information on the type of the building materials was obtained by inquiry. Three types of buildings were isolated: buildings built from wood, bricks and concrete or prefabricated products. In the analysis the number of years during which the patients and controls were living in these buildings was considered. No statistically significant correlation was noted between the risk of leukaemia development and the character of the building material. No increase was noted in this probability in relation to the time of living in a building built from any of these building materials. Additional analysis demonstrated that in Poland no so called "leukemic houses" are found, that is houses where during 5 years three of more cases of leukemia occurred. PMID- 2244172 TI - [Exposure to noise, vibration and radiation in Cracow]. AB - The problems are discussed connected with exposure to noise, vibration and ionizing radiation. In Cracow traffic and industrial noise is particularly troublesome. The greatest intensity of traffic noise is in the old part of the city and noise level caused by city transport is from 65 to 85 dB/A. Among the industrial sources of noise the highest intensity is in the Lenin Steel Plant, Leg Electrothermal Plant, and Solway Soda Works. Vibration and ionizing radiation resulting from the industrial activities are a considerable risk for human health in the Cracow area. The building materials in construction (including apartment houses) have sometimes a high radioactivity, e.g. dust-slag hollow bricks. The need is stressed for solving, if possible, the problem of noise, especially traffic noise, which is connected with considerable financial costs; the question of using materials of high radioactivity for building purposes should be also resolved. PMID- 2244173 TI - [Histidine decarboxylase activity and free histidine and histamine levels in fish meat]. AB - The activity of histidine decarboxylase was determined in the meat of fresh fish (mackerel, herring, sprat) and in fish stored for 48 hours at +4 degrees C and +18 degrees C. The activity was determined measuring the increase of histamine released from a controlled amount of histidine. A rise was demonstrated in the activity of these enzymes in the meat of fish stored for 48 hours at +18 degrees C. As a result of this activity the histamine level increased considerably, particularly in the meat of these fish species in which the free histidine content exceeds 100 mg/100 g of tissue. The mean activity of histidine decarboxylase obtained in the meat of frozen and fresh fish expressed in nmol of histamine/min/mg of protein was 0.11 +/- 0.06 for mackerel meat, 0.10 +/- 0.04 for herring, and 0.08 +/- 0.04 for sprat. PMID- 2244174 TI - [Modification of the test for determining bacterial capacity for nitrate reduction]. AB - For facilitation of the detection of bacteria able to reduce nitrates the presently used method of 24-hour broth culture with KNO3 and the method of growing on slant agar cultures with KNO3 (standard method) were compared, with certain modifications introduced. It was found that shortening of the incubation period from 24 to 6 hours and reduction of the volume of broth with KNO3 from 10 to 0.5 ml made possible obtaining of a greater number of correct results as compared to the standard method. In the 24-hour broth cultures with KNO3 done as yet in case of negative results it is indispensable to confirm them in the test with zinc dust. The placement of Griess reagents on points onto colonies growing on KNO3 agar may lead to false positive results. PMID- 2244175 TI - [Effect of cellulose on iron, zinc and copper metabolism in growing rats]. AB - The purpose of the study was determination of the effect of cellulose on the apparent absorption and tissue concentrations of iron, zinc and copper in growing rats. Male Wistar rats with initial body weight 108 +/- 2 g were fed during 6 weeks isocaloric diets containing 1%, 5% or 10% of dietary fibre. The diets contained about 18% protein (casein and wheat gluten 1:1) and iron 28 mg, zinc 17 mg and copper 4.5 mg per kg of diet. In the 2nd, 4th and 6th weeks of the experiment feaces were collected during 2 days. Mineral components of the diets, cases liver, spleen, kidneys and femur were determined by atomic absorption spectrophotometry. No significant differences were noted in diet intake or in body weight gain between these groups. Increased cellulose content in diet, that is 5% or 10%, reduced significantly the absolute and per cent apparent absorption of copper and its concentration in liver, which indirectly led to disturbances of iron metabolism. As a result, the concentration of haemoglobin was reduced and the hepatic iron reserve was raised. No adverse effect of cellulose was found on the apparent absorption of iron and zinc and on zinc concentration in the studied tissues. The per cent coefficients of apparent absorption of iron decreased during the experiment, while those of zinc and copper increased. PMID- 2244176 TI - [Distribution and elimination of C-14-2,4-dichlorophenoxyacetic acid (2,4 D) in rat tissues in acute poisoning]. AB - The authors carried out investigations for elucidating the distribution in the internal organs and tissues and the rate of the absorption from the digestive tract and elimination from the organism of 2,4-dichlorophenoxyacetic acid widely used in herbicides, to which man and animals are exposed. Radiometric investigations were carried out of the internal organs and tissues of male Wistar rats which were given one dose of the acid labelled with 14C one-third of LD 50/kg through an intragastric tube. The rats were killed at various time intervals for observing the rate of absorption and elimination of this compound. The measurements of radioactivity demonstrated high levels of the herbicide in the lungs, heart, liver, spleen and kidneys, and low levels in the adipose tissue and brain, with intermediate values in the adrenals and testicles. The compound is rapidly absorbed from the gastrointestinal tract reaching its highest level in the tissues after 6-20 hours, and is eliminated nearly completely already on the second day. Small residues of the acid and its metabolites containing 14C were present in the tissues up to the 20th day of the experiment. PMID- 2244177 TI - [Technical and sanitary conditions of food service facilities in nurseries in Poland 1975-1985]. AB - In the years 1975-1985 three times at intervals of 5 years the technical and hygienic condition was checked of the catering facilities of nurseries+ in a 40% randomly selected sample. The aim of the study was establishing whether in the years of increasing economic crisis, despite protective measures introduced by the authorities, detectable changes have taken place ot the advantage or disadvantage in the catering facilities, since a proper standard of this part of the nurseries is indispensable for a normal growth and health of children raised in institutions. In the first analysed 5-year period (1975-1980) some improvement was noted, especially in the technical equipment of these facilities. This was connected with greater investments provided for building of nurseries , resulting in a rise in the proportion of nurseries built according to the accepted building standard to 56%. In this way the number of nurseries with normal functional parameters increased. In the following 5-year period this condition was maintained owing to building of new nurseries although in lower number, while at the same time the worst creches were liquidated in areas where the requirements for places in creches have dropped. It was noted that in every third creche the catering facilities were below the accepted hygienic standard for such institutions, and this situation continued since several years. The quality and timing of meals were incompatible with the principles of rational nutrition already at the stage of menu planning. Activities should be taken for ensuring proper hygienic conditions in the catering facilities in creches and for improving the nutrition by correct composition of menu. PMID- 2244178 TI - Acetylsalicylic acid and the balance between prostacyclin and thromboxane A2. AB - Arachidonic acid is metabolized in endothelial cells to antiaggregatory, vasodilatory prostacyclin (PGI2), and in platelets to aggregatory, vasoconstrictory thromboxane A2 (TxA2). The balance of these two prostanoids is supposed to be involved with thrombogenesis and atherogenesis. Acetylsalicylic acid (ASA) inhibits irreversibly the key enzyme of the synthesis of these prostanoids, i.e. cyclo-oxygenase. Platelets do not synthetize new protein, but endothelial cells do. Because of this, and certain pharmacokinetic characteristics of ASA, it should be possible to shift the balance between PGI2 and TxA2 to the dominance of the former with the proper dose of this drug. Altogether more than 50,000 subjects have volunteered for studies on the effect of ASA in the primary or secondary prevention of myocardial infarction or ischemic stroke. The results show that it is possible to reduce vascular attacks by ASA. Furthermore, ASA has also found to prevent pre-eclampsia. Conclusions on the effect of ASA on the PGI2/TxA2-balance are hampered by uncertainties concerning the measurement PGI2 and TxA2 productions in vivo. It is, however, evident that the doses of ASA used in most trials have been high enough to inhibit partly also the production of PGI2. Whether smaller doses or less frequent administration would be more efficient, remains to be studied. PMID- 2244179 TI - The metabolic functions and mechanism of action of vitamin K. AB - Vitamin K functions in animal cells as the cofactor of the enzyme vitamin K dependent carboxylase which catalyzes the post-translational formation of gamma carboxyglutamyl (Gla) residues in specific vitamin K-dependent proteins. These proteins include four blood coagulation factors (prothrombin and Factors VII, IX and X), other plasma proteins (protein C, protein S and protein Z), two proteins from bone (osteocalcin or bone Gla-protein and matrix Gla-protein), and other proteins from lung, kidney, spleen, testis, placenta and other tissues. In the proteins involved in blood coagulation the Gla residues are mandatory for the activation of the inactive proenzymes; this process occurs on phospholipid surfaces to which the proenzymes are bound via Gla residues and calcium ions. The energy needed in the carboxylation reaction is obtained from the oxidation of vitamin K hydroquinone to 2,3-epoxide of the vitamin. Specific enzymes, vitamin K epoxide reductase and vitamin K quinone reductases, catalyze consecutive reactions in which the vitamin K hydroquinone is regenerated, thus allowing continued use of the vitamin K molecule for the carboxylations. The oral anticoagulants, derivatives of 4-hydroxycoumarin and indan-1,3-dione, used as therapeutic agents in thromboembolic disease, are antagonists to vitamin K preventing the catalytic use of vitamin K in the carboxylations by irreversibly inhibiting vitamin K epoxide reductase. PMID- 2244180 TI - The development of nuclear medicine imaging. AB - Great progress has been made in nuclear medicine imaging during the forty years this imaging modality has existed. Advances have been made both in the area of instrumentation and radiopharmaceuticals. The development started with a single detector system but now imaging devices can produce tomograms displayed three dimensionally on graphic monitors. The general trend in the production of radiopharmaceuticals has been the development of highly specific compounds for mapping of biological structures and functions. PMID- 2244181 TI - An emerging view of vitamin D. AB - Vitamin D3 (D2 is 22-ene,24-methyl D3) is a prehormone which is hydroxylated by mixed function mono-oxygenase NADPH-cytochrome P-450 ferredoxin/ferredoxin reductase systems in liver parenchyma and renal proximal tubular cells to 25 hydroxy, then 1,25-dihydroxyvitamin D, the active hormone. 1,25-dihydroxyvitamin D binds to a mainly intranuclear receptor in target cells [classically, bone, kidney and gut; now shown to be wider including parathyroid cells, endocrine cells generally and many cells of ectodermal (brain, skin) and mesodermal (blood forming cells, lymphnode cells) origin as well as tumour cells (breast, lymphoma, leukaemia)] and activates transcription for products such as calcium binding proteins, its own receptor protein, 24-hydroxylase and non-specific esterase which are active in calcium homeostasis and cell differentiation. Advanced methods for measuring components of the vitamin D endocrine system have been developed and involve column extractions, liquid chromatographic purifications (also HPLC) and protein and receptor binding assays as well as mass spectrometry. These have facilitated elucidation of vitamin D physiology (also in pregnancy and lactation) and of metabolic defects in classical, vitamin D resistant and renal rickets and osteomalacia, in sarcoidosis and in the possible involvement of the vitamin in cell differentiation, e.g. in myeloid leukaemia, and breast cancer. PMID- 2244182 TI - Developments in techniques for radioiodination of peptide hormones and other proteins. AB - This article presents details on two currently used methods of labelling peptides with radioiodine. The solid phase enzymatic iodination with lactoperoxidase is very suitable for radioimmunoassays and receptor assays. The iodogen labelling technique has been successfully used in this laboratory for preparing radioiodinated radiopharmaceuticals. Other iodination methods are also briefly discussed. PMID- 2244183 TI - Reference values, why and how. AB - A review describing the fallacies of the concept of normal values and the reasons for its substitution with reference values. The "reference value philosophy", its terminology and recommended practical procedures are presented and it is warned not to use incorrect terms such as "normal reference range". The concepts of health and disease are discussed from the point of view of the laboratory. Reference values are not always derived from "healthy" persons. In order to be comparable, reference values and observed (i.e. patient) values should be produced in the same way, using the same analytical procedure, quality control, etc. The influence of preanalytical factors such as food intake, posture, use of tourniquet and freezing and storing samples is great and necessitates standardisation of specimen collection. Strategies for the selection of reference individuals are presented and the reasons and methods for subdivision of the data are described. Descriptions are also given of the individual reference values and the statistical treatment of collected data including multivariate analysis. Finally, the reporting of observed values in relation to reference values is discussed. There is a trend to avoid the use of the reference interval because of the temptation to regard the values falling outside it as pathological. PMID- 2244184 TI - 1,5-Anhydro-D-glucitol--a novel type of sugar in the human organism. AB - 1,5-Anhydroglucitol is a six-carbon chain monosaccharide in C1-chair conformation with an oxygen ring in pyran position. The compound is a component of normal human blood serum. The concentration in serum fluctuates within a narrow range in a normal population. Very low serum concentrations are found in patients with diabetes mellitus. In insulin-dependent (type 1) diabetes with a long history of disease the concentration of 1,5-anhydroglucitol remains low in spite of improvement of glycaemic control by intensification of treatment, whereas in non insulin dependent (type 2) diabetes the concentration gradually increases towards normal levels concomitantly with improvement in glycaemic control. The serum 1,5 anhydroglucitol concentration may be useful as an indicator of glycaemic control in patients with non-insulin dependent diabetes. Urinary excretion of 1,5 anhydroglucitol in normal subjects is very low inferring that the compound is efficiently reabsorbed by tubular cells. During glucosuria, induced by glucose tolerance test in human or streptozotocin administration in rats the 1,5 anhydroglucitol excretion is temporarily increased, which may be attributable to a competition between 1,5-anhydroglucitol and glucose for renal tubular transporters. Data so far obtained indicate that 1,5-anhydroglucitol may be either actively or passively transported through the cell membrane, depending on the cell type. Gas-liquid chromatography is the method of choice in the measurement of the low concentrations of 1,5-anhydroglucitol present in biological samples. PMID- 2244185 TI - Heme in the treatment of heme deficiency states. AB - The mechanism of regulation of heme biosynthesis is of great interest for both biological and medical reasons. The hepatic and erythropoietic porphyrias are shown to be hereditary or acquired disorders characterized by defects in specific enzymes of the heme biosynthetic pathway. In addition, several other diseases can be associated with a defect of heme biosynthesis. Heme has become well established in the treatment of acute porphyrias. In recent years, heme has been used increasingly for the treatment of other heme deficiency states as well. PMID- 2244186 TI - Endogenous interference in immunoassays in clinical chemistry. A review. AB - The increasing availability and use of immunoassays in clinical chemistry have revealed a number of endogenous interferences. Solid-phase sandwich immunoassays based on monoclonal antibodies are particularly sensitive to any factor able to bridge immunoglobulins together. Heterophilic immunoglobulin antibodies have been demonstrated in up to 40% of patient samples and to cause spuriously elevated results unless certain precautions are taken. Rheumatoid factors belong to the same category, but their affinity is usually too low to cause significant interference. Immunoscintigraphy generates high-titre anti-immunoglobulin responses causing serious interferences in immunoassays. Recently interfering factors of unknown nature causing nonspecific binding of enzyme-labelled antibodies have been observed. Spuriously decreased values can be caused by complement, which may interfere with antigen-binding to solid phase antibody. The aforementioned and other endogenous interferences in immunoassays are reviewed and methods for their elimination discussed. PMID- 2244187 TI - Assessment of thyroid status by laboratory methods: developments and perspectives. AB - Serum protein-bound iodine and in vivo radioiodine tests were employed for over three decades although their usefulness was hampered by interference from iodinated compounds. Tests reflecting thyroid hormone action were therefore used for additional information on thyroid status. Competitive saturation analysis of serum T4 was introduced in the 60s. RIAs for T4 and T3 were not developed until ten years later because of problems in raising polyclonal antibodies to small haptens. Methods for FT4 and FT3 based on equilibrium dialysis of serum labelled with radioiodinated hormone emerged in the 60s, and in the 70s sensitive RIAs enabled direct determination of free hormone concentrations in serum dialysate. Dialysis and ultrafiltration methods are tedious and therefore various free hormone indices, based on total hormone concentrations and tests for unoccupied thyroid hormone-binding sites, have been used right up to our times. In the 80s rapid assays for FT4 and FT3 based on varying principles were developed particularly by commercial companies. Free hormone assays utilizing thyroid hormone analogs as tracers have been criticized because binding of analogs to serum proteins results in spurious values in conditions characterized by thyroid hormone-binding protein abnormalities. Bioassay of TSH was not adopted by the clinical service laboratory because of insufficient analytical sensitivity. The first immunological TSH assay, based on cross-reaction of human and bovine TSH in a hemagglutination inhibition test, was also too insensitive for practical purposes. RIAs for direct determination of normal TSH concentrations were developed in the 60s. The breakthrough in measurement of low TSH concentrations occurred in the 80s with the advent of immunometric assays utilizing monoclonal antibodies. Recently chemiluminescence, fluorescence and enzyme labels have been used for the development of non-isotopic methods for thyroid hormones and TSH. Immunoassay systems for bed-side measurement of analyte concentrations are being developed and immunosensors for continuous monitoring of analyte levels will probably be available in the future. PMID- 2244188 TI - Tumour-associated trypsin inhibitor and tumour-associated trypsin. AB - Tumour-associated trypsin inhibitor (TATI) is a 6 kDa peptide, which is synthesized at low concentrations by several tumours and cell lines. Very high concentrations of TATI occur in mucinous ovarian tumours. Elevated levels of TATI occur in serum and urine in connection with most types of cancer at advanced stages. In mucinous ovarian cancer up to 85% of all cases have elevated serum levels. Because high levels also occur in early mucinous ovarian cancer TATI appears to be the marker of choice for this tumour. Elevated levels may also occur in nonmalignant disease, especially in patients with severe infections, tissue destruction and pancreatitis. Production of TATI in tumours is associated with expression of two new tumour-associated trypsin(ogen) (TAT) isoenzymes, TAT 1 and -2, TAT-2 being the major form. These enzymes are immunologically similar to trypsinogen-1 and -2, respectively. They activate prourokinase and may therefore trigger the tumour-associated protease cascade contributing to the invasiveness of malignant tumours. PMID- 2244189 TI - Two-point discrimination test. A valuable part of hand surgical rehabilitation, e.g. in tetraplegia. AB - In assessing the prospects for surgical and other kinds of rehabilitation in tetraplegia and stroke patients the two-point discrimination test, correctly performed by experienced examiners, is of great value. Valid and repeatable results depend on exact technique and proper tools. There is a firm correlation between the thresholds of two-point discrimination on the pulps of the fingers and the accuracy of position sense at the metacarpophalangeal and interphalangeal joints. Microneurography has shown that cutaneous receptors have proprioceptive as well as exteroceptive functions. Thus the two-point discrimination test can be used as a measure of proprioceptive function. The results can be expressed numerically. A two-point threshold less than 10 mm on the pulp is a valid measure of useful finger proprioception. It also shows tactile gnosis, necessary for precision sensory grips. PMID- 2244190 TI - Important predictors of the outcome of physical training in patients with intermittent claudication. AB - Hemodynamic and endocrine variables have been unsuccessful to predict improvement in walking distance in patients with intermittent claudication following structured training programs. In the present study we evaluated the predictive value of a number of hemodynamic and endocrine parameters. In addition we included information on cognitive factors such as stress and the belief in the structured training and motivation to participate. Twenty-five elderly subjects were studied. Significant improvement in overall walking distance was achieved. The most important explanatory variables of relative improvement in walking distance were belief in training, initial walking distance and number of smoke years. The results support the belief that cognitive factors are of major importance in predicting functional effects of structured training programs for patients with intermittent claudication. PMID- 2244191 TI - The effect of steering on the physiological energy cost of wheelchair propulsion. AB - Previous studies of the energy cost of wheelchair propulsion have used ergometers or tracks requiring little steering. We have measured minute ventilation (VE), oxygen consumption (VO2), carbon dioxide output (VCO2) and heart rate (HR) during exercise in a two arm, hand-rim propulsion wheelchair on a treadmill, and on three tracks of increasing tortuosity in eight able-bodied subjects. During propulsion at 0.6 m/sec, VE, VO2, and VCO2 were significantly greater on the track with the maximal steering component than on that with the minimal steering component, or on the treadmill with no steering component. Heart rate was significantly higher on the maximal compared to minimal steering component track. Exercise at speeds varying from 0.2 to 1.0 m/sec showed that VO2 and VCO2 were significantly higher on the medium steering component track than on the treadmill at speeds of 0.6 m/sec and above. We conclude that the effort of steering contributes significantly to the energy cost of wheelchair propulsion particularly at higher speeds. PMID- 2244192 TI - Detrusor pressure in cystometry compared to physiological filling in patients with a reflex urinary bladder after spinal cord injury. AB - The maximum detrusor pressure and the duration of detrusor contractions in 10-50 ml/min fill cystometry were compared to the corresponding measurements during 12 hours of physiological filling, in 18 patients with a reflex urinary bladder after spinal cord injury. In four consecutive cystometries with 10 min intervals the intraindividual variation of the maximum detrusor pressure and the duration of detrusor contractions were similar to the variation during physiological filling. The mean pressure values in cystometries of each patient correlated well with the mean values in registration during physiological filling. In cystometry, there was no significant difference between mean values in 50 ml/min filling compared to 10 ml/min filling nor between mean values in first and second cystometries compared to third and fourth cystometries. Thus, mean values from a series of 10 ml/min or 50 ml/min fill cystometries appear to be as useful as registrations during physiological filling to describe the mean maximum detrusor pressure and the mean duration of contractions in a patient with a spinal reflex bladder. PMID- 2244193 TI - Respiratory function in chronic primary fibromyalgia. AB - Since patients with severe chronic primary fibromyalgia (CPF) report effort dyspnoea, respiratory function was studied in 87 consecutive women with CPF according to Yunus' criteria. Bernstein spirometry, maximum inspiratory (MIP) and expiratory (MEP) pressures were obtained in patients, and in a reference group of 61 healthy women. MIP was considerably lower in patients than in controls (3.6 +/ 2.0 vs. 8.0 +/- 2.2 kPa, p less than 0.0001), as was MEP (3.1 +/- 2.1 vs. 8.3 +/ 2.2 kPa, p less than 0.0001). Patients who had previously reported dyspnoea at a bicycle exercise test showed significantly lower values of respiratory pressures than patients without dyspnoea. Respiratory pressures were reproducibly low in CPF patients. Spirometric values were normal among patients and controls. We conclude that maximum expiratory and inspiratory pressures are low in CPF, a finding which may indicate respiratory muscle dysfunction in this syndrome. PMID- 2244194 TI - The hip joint: forces needed for distraction and appearance of the vacuum phenomenon. AB - Joint traction and other mobilization techniques are commonly used in physical therapy for patients with osteoarthrosis. The aim of this study has been to: (a) measure the separation of the joint surfaces in the normal hip joint during application of different forces; (b) investigate whether or not the degree of separation was influenced by the position of the joint; (c) compare hip joint laxity in men and women; (d) find the traction force needed to cause the appearance of vacuum phenomena. To achieve a separation in the hip joint, a traction force of at least 400 N must be applied. The distraction was greater in the loose packed position than in the close packed position at equal force and in both males and females. Vacuum phenomena appeared at between 400 and 600 N of traction, varying with joint position. PMID- 2244195 TI - Individualized adaptation of clothes for impaired persons. A comparison of two groups with and without experience of adapted clothes. AB - Impaired persons often have difficulties in obtaining suitable clothing. Questionnaires on this subject were sent to a consecutive series of impaired persons. Group 1 (n = 50) had received adapted clothes and group 2 (n = 81) had not. Questionnaire A (both groups) contained general questions on clothes and questionnaire B (Group 1) contained questions on adapted clothes. The result of the study shows a significant difference (p less than 0.01) between the need for adapted clothing in group 1 and group 2. No significant difference was found between the groups regarding the reason for obtaining and using adapted clothes. It was difficult for 94% in group 1 and 85% in group 2 to obtain clothes which were suitable for the individual's impairment and which made their daily activities easier. In group 1 the adapted garments were of most value when dressing and undressing (86%). They also reduced the time needed, by 31% for the individual, by 43% for a helper; and by 62% when going to the toilet. The adapted garments were considered smarter and more comfortable by 64%. Eighteen per cent considered that wearing them had increased their self-confidence. PMID- 2244196 TI - [Subcortical origin of orientation sensitivity of visual cortex]. PMID- 2244197 TI - [Movement characteristics of the spermatozoa]. PMID- 2244198 TI - [Highlights of thromboxane synthetase inhibitor research]. PMID- 2244200 TI - [Cerebral microcirculation]. PMID- 2244199 TI - [Relation between vegetative nervous activities and coronary spasm]. PMID- 2244201 TI - [Classification, distribution and functions of 5-hydroxytryptamine receptors]. PMID- 2244202 TI - [Anabolism of pulmonary surfactant]. PMID- 2244203 TI - [Research on potential preproenkephalin processing enzyme in adrenal medulla chromaffin granules]. PMID- 2244204 TI - [Physiological and clinical aspects of gastrointestinal hormone receptors]. PMID- 2244205 TI - A storm over steroid therapy. PMID- 2244206 TI - NIH readies plan for cost containment. PMID- 2244207 TI - Biology goes to the movies. PMID- 2244208 TI - Genetic defect identified in rare cancer syndrome. PMID- 2244209 TI - Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. AB - The Wilms' tumor locus (WTL) at 11p13 contains a gene that encodes a zinc finger containing protein that has characteristics of a DNA-binding protein. However, binding of this protein to DNA in a sequence-specific manner has not been demonstrated. A synthetic gene was constructed that contained the zinc finger region, and the protein was expressed in Escherichia coli. The recombinant protein was used to identify a specific DNA binding site from a pool of degenerate oligonucleotides. The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli. A mutation in the zinc finger region of the protein originally identified in a Wilms' tumor patient abolished its DNA-binding activity. These results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process. PMID- 2244210 TI - Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors. AB - The current studies were designed to determine whether chronic overexpression of low density lipoprotein (LDL) receptors in the liver would protect mice from the increase in plasma LDL-cholesterol that is induced by high-fat diets. A line of transgenic mice was studied that express the human LDL receptor gene in the liver under control of the transferrin promoter. When fed a diet containing cholesterol, saturated fat, and bile acids for 3 weeks, the transgenic mice, in contrast to normal mice, did not develop a detectable increase in plasma LDL. The current data indicate that unregulated overexpression of LDL receptors can protect against diet-induced hypercholesterolemia in mice. PMID- 2244211 TI - A borna virus cDNA encoding a protein recognized by antibodies in humans with behavioral diseases. AB - Borna disease virus (BDV) causes a rare neurological disease in horses and sheep. The virus has not been classified because neither an infectious particle nor a specific nucleic acid had been identified. To identify the genome of BDV, a subtractive complementary DNA expression library was constructed with polyadenylate-selected RNA from a BDV-infected MDCK cell line. A clone (B8) was isolated that specifically hybridized to RNA isolated from BDV-infected brain tissue and BDV-infected cell lines. This clone hybridized to four BDV-specific positive strand RNAs (10.5, 3.6, 2.1, and 0.85 kilobases) and one negative strand RNA (10.5 kilobases) in BDV-infected rat brain. Nucleotide sequence analysis of the clone suggested that it represented a full-length messenger RNA which contained several open reading frames. In vitro transcription and translation of the clone resulted in the synthesis of the 14- and 24-kilodalton BDV-specific proteins. The 24-kilodalton protein, when translated in vitro from the clone, was recognized by antibodies in the sera of patients (three of seven) with behavioral disorders. This BDV-specific clone will provide the means to isolate the other BDV-specific nucleic acids and to identify the virus responsible for Borna disease. In addition, the significance of BDV or a BDV-related virus as a human pathogen can now be more directly examined. PMID- 2244212 TI - Community health care and hospital attendance: a case study in rural Ghana. AB - This study assesses the influence of coverage with a network of PHC clinics as well as private clinics in Dormaa District, Ghana on, hospital attendance. This influence is measured by analysing hospital attendance among inhabitants during 6 months in 1984 and 1986. Several conditioning factors are analysed: the type of modern health care present in the community and the experience of the community health worker (CHW); the distance between community and hospital; the time factor (1984 and 1986); the sex and age of the attendants; the diagnosis made at the hospital. It appears that fewer people attend the hospital if a community participates in the PHC programme and if the CHW is experienced. When people from these communities attend the hospital they do so less unnecessarily than those from other communities. Simple analysis of routine hospital data may contribute to any PHC assessment programme set up around the hospital. PMID- 2244213 TI - Patient initiatives and physician-challenging behaviors: the views of Israeli health professionals. AB - The views of Israeli physicians, nurses, physiotherapists, occupational therapists, and medical social workers were compared regarding patient behaviors which express autonomy and initiative in the doctor-patient interaction. The data show that these professionals do not view such behaviors positively. Gender is relevant to the physicians' views, with male physicians, particularly the specialists, having the least negative views, and female residents and general practitioners the most negative. Allied health professionals express less negative views than the physicians, and attribute to the physicians more negative views than those actually expressed by the physicians. There is overall agreement among the different professional groups about the relative acceptability of these behaviors. Those which threaten the physician's dominance in the process of diagnosis and prescription of treatment are rejected outright, while others are tolerated but not accepted. The findings are interpreted in the light of the status-related motives of Israeli health professionals. PMID- 2244214 TI - Modernization and catecholamine excretion of young Samoan adults. AB - Urinary catecholamine excretion rates have been used as a cross-culturally valid measure of generalized stress. The purposes of this paper are to examine group differences in catecholamine excretion rates in three Samoan groups who differ in degree of modernization and to compare these findings to rates of norepinephrine and epinephrine excretion in other populations. In 1986-1987, 24-hr urine samples were collected from 18-37-year-old Samoans; 46 rural Western Samoan villagers, 53 American Samoans, and 49 Samoans residing in Honolulu. The results show that norepinephrine excretion is significantly higher in more modernized Samoan groups (P less than 0.05), while epinephrine excretion is not significantly different in the three groups. The higher norepinephrine excretion rate in the more modernized Samoan groups may be related to differences in relative work load associated with changes in body weight, work capacity, and work patterns which accompany modernization. Samoan epinephrine excretion rates are relatively high compared to the results of other population studies, while norepinephrine excretion in three Samoan samples ranged from among the lowest rates observed worldwide to among the highest. PMID- 2244215 TI - 'Codes' and practice: information in drug advertisements--an example from Sri Lanka. AB - The amount of scientific information that should appear in an advertisement for a drug has been discussed for over 20 years. The information should promote the rational use of the drug. There is a lack of data from developing countries. We analysed all drug advertisements in the Ceylon Medical Journal (CMJ) 1985-1986. Conformity with the existing WHO guidelines and IFPMA code was also assessed. The 111 advertisements constituted 42% of the pages in the CMJ. Thirty-one of 34 companies were from the industrialized nations. Twenty-one per cent of the advertisements did not have the generic name; 94% had information on indications, whereas only 23 and 22% had information on adverse effects and contraindications. Only 16% provided information on generic name, indications, dosage, adverse effects and contraindications. Despite this 68% satisfied the criteria of the WHO guidelines and IFPMA code mainly under an ill defined 'reminder advertisement' clause. The existing guidelines are insufficient to ensure the minimum scientific information in drug advertisements. PMID- 2244216 TI - Preferences for health care involvement, perceived control and surgical recovery: a prospective study. AB - In a sample (N = 75) of coronary bypass patients, we examined the manner in which preoperative perceptions of personal control over recovery, desires for behavioral involvement in health care, and desires for information about health care predicted recovery in the hospital. Results indicated that preoperative control beliefs and desires for health care involvement predicted independently several important indices of recovery. Specifically, patients who prior to their surgery expressed a greater desire for information tended to experience less surgical pain and more negative psychological reactions. Greater preferences for behavioral involvement were associated with greater pain behavior, more ambulation, and shorter hospital stays. Finally, greater perceived personal control over recovery was associated with a shorter hospital stay. PMID- 2244217 TI - Health status and the housing system. AB - Most research on housing and health seeks causal links between dwelling conditions and the incidence of physical and mental disease. Less attention has been paid to the more sociological question of how health status affects housing opportunities. This paper shows how, and considers why, medical factors influence access to housing, whether in the public sector (where accommodation is traditionally allocated according to 'need') or in the housing market (where dwelling availability depends on ability to pay). In Britain, whose experience is taken as an example, a shrinking council housing stock can no longer accommodate general medical needs. Consequently, notwithstanding the importance of 'special' housing initiatives, many sick people are forced to seek accommodation in the private sector. Whether they succeed or fail (and so become homeless), this raises questions concerning the health selective role of the housing system which analysts have scarcely begun to address. PMID- 2244218 TI - Caring for the elderly: the partnership issue. AB - The promotion of a partnership set up to assure care for dependent elderly people has become a popular topic amongst health care and social services planners. This paper reviews what seems to be Quebec's main assumptions concerning the demands created by the demographic explosion of elderly people, limited financial resources, and the negative impact of institutionalisation. The state's five guidelines for the establishment of sensible health care services for dependent elderly people are also discussed. They include redefining the '65 years or over' criterion that labels someone in this age group as 'a person needing extra care services'; cutting and re-allocating state expenditures; soliciting all eventual partners outside the formal health care network; reformulating the roles and duties of health care professionals, stressing the efficiency of their intervention; and re-asserting the value of an elderly person's family and community networks. An interpretation of the meaning of partnership, based on information in government documents, as well as the conditions that could hinder its development are also discussed. Finally, an overview is provided of the potential effects of a partnership on the target group and the community. This analysis is based on Quebec's situation although many of the angles and dilemmas could be applied to other industrialised countries. PMID- 2244219 TI - Spatial patterns of attendance at general practitioner services. AB - Geographical theory suggests that consumers will travel to the centre nearest to their residence which offers a particular service. This is a weak indicator of surgery attendance patterns in Gisborne, New Zealand. Nearby surgeries were attended, rather than the nearest available. Various attributes of the practices and the patients were examined to discover their influence on attendance patterns. The distribution of the practices themselves had a significant effect upon relative surgery attendance. Prior knowledge of services was particularly important in determining surgery selection and continued attendance. This accounted for the spatially unconstrained attendance of many Maori. Greater personal mobility enabled higher income households to travel further to attend. Conversely, the less mobile were spatially bounded. PMID- 2244220 TI - Female autonomy and child nutritional status: the extended-family residential unit in Amman, Jordan. AB - This study explores the hypothesis that the mother's position within household power relations--her autonomy with respect to other household members--influences her ability to provide for the health of her children. We argue that in the context of the Arab Middle East, a woman's structural position within the household is a good indicator of her relative autonomy: if she is the daughter-in law in a vertically extended residential unit, she has less autonomy than if she is head or co-head of household. Our analysis is based on data collected from 1341 households in 1985 as a part of the Follow-up Health and Population Assessment of four urban settlements in Amman, Jordan. They include measures of the child's weight and age, plus a variety of socioeconomic factors. We analyze the effect of the mother's autonomy on child nutritional status within a multiple regression framework that controls for rival hypotheses. In particular, we investigate whether it is the availability of other potential child-care substitutes, particularly the grandmother, that influences child nutrition rather than household structure. We also look at household income, mother's education, the area of residence, and the child's sex. Our results show a strong negative influence associated with having a mother whose autonomy in the household is low. This effect does not disappear when mother's age and education, and household size and composition are taken into consideration. Nor is it a proxy for the higher household incomes characteristic of extended-family residential units with their multiple earners. PMID- 2244221 TI - Knowledge regarding organ donation: identifying and overcoming barriers to organ donation. AB - Four-hundred and fifty-five undergraduate students, 26 MBA students, and 465 people from the surrounding community responded to 21 true/false questions regarding factual knowledge about organ donation. The mean number of correct answers was 74.6%. The correct response rate, however, varied widely over questions. Four questions with very large error rates suggest possible 'barriers to donation'. Specifically, these questions concerned religious support for organ donation, the concept of brain death, the normally rigid separation of physician teams who are primarily responsible for the welfare of the donor and donee, and a mistaken belief that to be valid an organ donor card must be filed with the U.S. Department of Health and Human Services. Knowledge of organ donation facts was found to be related to whether subjects carried or requested an organ donor card, their attitude towards organ donation and their willingness to donate their own organs or the organs of a deceased loved one. These findings suggest strategies for raising public support for organ donation. PMID- 2244222 TI - Urban desertification, public health and public order: 'planned shrinkage', violent death, substance abuse and AIDS in the Bronx. AB - Techniques and approaches from population and community ecology, along with theoretical viewpoints from criminology and the 'social support hypothesis' of health maintenance, are used to examine recent patterns of rising homicide and suicide, intensified substance abuse, low birth weight and AIDS deaths in the Bronx section of New York City. Empirical and theoretical analyses strongly imply present sharply rising levels of violent death, intensification of deviant behaviors implicated in the spread of AIDS, and the pattern of the AIDS outbreak itself, have been gravely affected, and even strongly determined, by the outcomes of a program of 'planned shrinkage' directed against African-American and Hispanic communities, and implemented through systematic and continuing denial of municipal services--particularly fire extinguishment resources--essential for maintaining urban levels of population density and ensuring community stability. This work complements a recent study by McCord and Freeman [1. New Engl. J. Med. 332, 173, 1990] on Harlem, and suggests the present overburdening of New York's criminal justice system arises from almost exactly the same causes as its accelerating inability to meet demands for acute medical service, so-called 'medical gridlock', in that both are expressions of the increasing social disorganization of poor communities initiated and continued in considerable part by government policy. The critical role played by improper policy in triggering the syndrome suggests ecologically informed interventions, particularly essential service restoration, may hold the potential for great positive impact. PMID- 2244223 TI - Patterns of care for chronic patients after the Italian psychiatric reform. A longitudinal case register study. AB - A comprehensive and well-integrated community-based system of psychiatric services has been developed in South-Verona since the Italian psychiatric reform. Using the South-Verona Psychiatric Case Register, we identified chronic psychiatric patients in the community over a 6-year period after the reform. Six first-contact sociodemographic variables (sex, age, marital status, living situation, education, occupational status) and two clinical variables (ICD-9 diagnosis and past history of state psychiatric hospital admission) were studied for these patients. Four full cohort-years of post-reform chronic patients were followed for a 2-year period to determine their subsequent patterns of care. Logistic analysis was used to examine the interaction of cohort-year with outcome and the above sociodemographic and clinical variables studied individually and in combination. We found that 36.4% of post-reform chronic patients in the community remained in long-term contact with psychiatric services for 2 years after they were first identified. Logistic analysis revealed that none of the sociodemographic and clinical variables studied individually or in combination were predictive of the probability of remaining in long-term contact with community psychiatric services. PMID- 2244224 TI - Evaluation of rational drug prescribing in Democratic Yemen. AB - The government of Democratic Yemen started an essential drugs programme in 1984. Every month quantities of 30 drugs are delivered in prepacked kits to health units and standard treatment schedules have been agreed. The quantities of each drug were estimated by applying the standard treatment schedules to the typical morbidity patterns seen at these facilities. Most health workers attended a training course on the correct use of the standard treatment schedules. Hospital and health centres have been included in the programme to a more limited extent. In March 1988 an evaluation of the programme was carried out. Comparisons were made between random samples of health units included in the programme and those where it had not yet been implemented. The adequacy of knowledge necessary for reasonable use of drugs was assessed by interviewing health workers. Actual drug prescription was studied by means of quantitative indicators. A more qualitative insight was obtained by reviewing drug prescriptions for four tracer diseases at a sample of health centre and hospital out-patient departments. Health workers at units included in the programme had significantly (P less than 0.05) higher levels of rational drug knowledge and 'better' actual drug prescription in terms of proportions of patients receiving injections (25% vs 58%), antibiotics (45% vs 67%) and the average number of drugs per patient (1.5 vs 2.4)--all P less than 0.001. Many patients treated at health centres and hospitals were receiving irrational drug treatment for the tracer conditions. It is suggested that the methods used in this evaluation to measure rational drug prescription could be appropriate in the assessment of other essential drugs programmes. PMID- 2244225 TI - [An important decline]. PMID- 2244226 TI - [Franco-British Colloquium. The Law of 1983]. PMID- 2244228 TI - [Psychiatric revolution? Readjustments, decline of psychiatry]. PMID- 2244227 TI - [Scottish legislation]. PMID- 2244229 TI - [Clinical practice in pediatric psychiatry]. PMID- 2244231 TI - [The question of old age]. PMID- 2244232 TI - [Mental health in Europe. Comparative and multidisciplinary approaches]. PMID- 2244230 TI - [Intervention in the psychiatric crisis]. PMID- 2244233 TI - [Admission and crisis centers]. PMID- 2244234 TI - [Experiments in art therapy]. PMID- 2244235 TI - [Evaluation of mental health]. PMID- 2244236 TI - [The social life of persons afflicted by schizophrenia]. PMID- 2244237 TI - [Community care in Great Britain]. PMID- 2244238 TI - [Nursing care. Its perception by the patients]. PMID- 2244239 TI - [Project 2000. New training for nurses]. PMID- 2244240 TI - [12 years at the U.F.R. of Bobigny]. PMID- 2244242 TI - [Responsibility of the psychiatric nurse. Role and function of the nurse]. PMID- 2244241 TI - [Responsibility of the psychiatric nurse. Psychiatric nursing care outside the hospital]. PMID- 2244243 TI - [Responsibility of the psychiatric nurse. Legal responsibility of the nurse]. PMID- 2244244 TI - [Crisis in community care in Great Britain]. PMID- 2244245 TI - [Imaging technique in 3-dimensional cranial CT]. PMID- 2244246 TI - [3D-reconstruction in computed tomography as a diagnostic plus in traumatology?]. PMID- 2244247 TI - [Spiral-CT: a new technique for volumetric scans. II. Potential clinical applications]. PMID- 2244248 TI - [50 years of x-ray mass screening]. PMID- 2244249 TI - [Clinical observations on the topic of informing cancer patients]. PMID- 2244250 TI - [Rheumatology as an interdisciplinary science]. PMID- 2244251 TI - [A simplified method for the assessment of C1 esterase inhibitor function]. AB - From the result that the activated form of C1-s(C1-s) prolonged the kinetics of hemolysis via complement, this assay was applied to assess C1 esterase inhibitor (C1INH) function. In the kinetic assay, the complement hemolytic activity was evaluated by the time which required to cause 50% reduction of the initial turbidity of sensitized sheep erythrocytes, and was expressed as T1/2. (1) T1/2 of pooled normal human sera (p-NHS) showed dose-dependent prolongation by the addition of various amounts of C1-s. (2) Preincubation of various amounts of functionally pure C1INH with the constant amounts of C1-s inhibited dose dependently the prolongation of T1/2 by C1-s. (3) The C1INH activity of NHS was 840 +/- 80 units/ml (n = 6) and that of the C1INH deficient serum was 80 units/ml, which were calculated from the standard curve established by the addition of various amounts of purified C1INH. This test requiring only C1-s and sensitized sheep erythrocytes is simple technically and high in sensitivity, and seems to be useful for the routine assay for C1INH function of human sera. PMID- 2244252 TI - [Low dose methotrexate therapy in rheumatoid arthritis]. AB - Twenty-three patients were included in this prospective study about the safety and efficacy of oral low dose methotrexate (MTX) in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 6.6 +/- 1.8 (SD) mg weekly over a mean duration of 16.6 +/- 12.5 months. Patients improved significantly in all clinical parameters of efficacy. There were significant reductions in Lansbury joint scores (p less than 0.001), duration of morning stiffness (p less than 0.001), sedimentation rates (p less than 0.001), C reactive protein (p less than 0.01), IgG(p less than 0.01), rheumatoid factor (p less than 0.01) and significant increase in grip strength (p less than 0.001), hemoglobin (p less than 0.05) after 17 months of treatment with MTX. Radiographic progression of joint disease were assessed using global scoring method. The mean rate of development of erosions and joint-space narrowing during MTX therapy was significantly less than the rate of radiographic progression before MTX therapy (8.1 +/- 7. 9/year vs. 1.9 +/- 3.8; p less than 0.05). Adverse reactions during MTX therapy included transient transaminase elevation (17.4%). Five patients (21.7%) were withdrawn because of leukopenia (2), interstitial pneumonitis (1), stomatitis (1), skin rash (1). We conclude that low-dose methotrexate is effective for the management of clinical disease activity in patients with refractory rheumatoid arthritis and may be a disease-modifying anti-rheumatic drugs (DMAR-Ds) by roentgenographic criteria. PMID- 2244253 TI - [Morphologic transformation of renal lesions by steroid treatment and its therapeutic implication in a patient with lupus nephritis]. AB - When we perform renal biopsy in patients with lupus nephritis (LN), we use the histopathological findings in glomerulus for the choice and dosage of steroid and immunosuppressive therapy. Recently, we experienced a case of LN who underwent three times of renal biopsy and had received various dosages of steroid. Our therapy resulted in her renal function deteriorated over 5 years. In detail, the patient was a 45-year-old female and the first renal biopsy was performed at the active stage of LN with nephrotic syndrome and serological activities. The biopsy specimen showed membranous LN accompanied by mesangial proliferation, necrosis, cellular crescents and intramembranous deposits. Thus, large dose of steroid including pulse therapy was given, and subsequently massive proteinuria and serological activities subsided gradually. However, 4.0 g of proteinuria per day remained in the patient. Accordingly, the second biopsy was done at one and half years later and it showed the regression to nearly pure membranous LN with thickening of glomerular basement membrane and only mild increment of mesangial matrix. Thus, she remained on 15 mg of daily prednisolone. Eventually, she progressed to 2.3 mg/dl of serum creatinine in renal function. The third biopsy was undertaken 5 years later and it showed sclerosing LN with tubular atrophy. Based upon these serial morphologic alterations in LN, we presumed that steroid treatment per se was not adequate for the control of this type of LN and new additional therapy including cytotoxic drugs is probably needed for the improvement of these glomerular lesions. PMID- 2244254 TI - [An autopsied case of PSS associated with Sjogren's syndrome and secondary generalized amyloidosis]. AB - Fifty year-old female with progressive systemic sclerosis associated with Sjogren's syndrome who died of meteorism, diarrhea, bleeding of digestive canal due to amyloid deposition in the intestine and jaundice was reported. Autopsy revealed pathological findings compatible with that of PSS and Sjogren's syndrome. Furthermore, deposition of amyloid materials were shown in tissue of digestive canal, thyroid gland, heart muscles, lymphnodes, and small vessel wall of the whole body. Amyloid material was demonstrated to be A-A protein based upon the loss of Congo red stain after exposure to potassium permanganate, and reaction to anti A-A protein antibody. Although obstruction of intrahepatic bile duct, especially in Hering canal, could be relating to some unknown factors secondary to intestinal amyloidosis, further studies will be required to clarify the pathogenesis of it. PMID- 2244255 TI - [Two cases of amyopathic dermatomyositis with fatal rapidly progressive interstitial pneumonitis]. AB - Two middle-aged women showed typical erythematous heliotrope eruption and Gottron's sign without any symptom of myositis. The patients were diagnosed as 'amyopathic dermatomyositis' because of normal serum CPK levels, normal EMG and no histological abnormality by muscle biopsy. Clinical manifestations improved by the treatment with corticosteroids. During tapering of corticosteroids, however, intersititial pneumonitis developed and rapidly progressed. The first patients was treated with methylprednisolone pulse therapy, azathiopurine and methotrexate. The second patients was treated with betamethazone, methlprednisolone pulse therapy and cyclosporin A. In spite of these extensive immunosuppressive therapies, both patients died of pulmonary insufficiency a few months after admission. In the literature there has been only several cases of amyopathic dermatomyositis and only one case with fatal rapidly progressive interstitial pneumonitis. A new approach to the treatment of this disease should be made. PMID- 2244256 TI - [Magnetic resonance imaging of the spine in rheumatoid arthritis]. PMID- 2244257 TI - [Distressing uterine contractions in a pregnant woman]. PMID- 2244258 TI - [Pediatric S.M.U.R. (Mobile Services for Emergencies and Resuscitation). When to call?]. PMID- 2244259 TI - [Resuscitation in the delivery room]. PMID- 2244260 TI - [Antenatal pediatric assistance]. PMID- 2244261 TI - [Infantile respiratory distress]. PMID- 2244262 TI - [Acute dehydration in infants]. PMID- 2244263 TI - [Pediatric S.M.U.R. (Mobile Services for Emergencies and Resuscitation)]. PMID- 2244264 TI - [Purpura fulminans]. PMID- 2244265 TI - [Coma and neurological disorders]. PMID- 2244266 TI - [Allergies in children]. PMID- 2244267 TI - [Congenital cardiopathies]. PMID- 2244268 TI - [Cardio-respiratory arrest in children. Management]. PMID- 2244269 TI - [Pediatric S.M.U.R. (Mobile Services for Emergencies and Resuscitation) in the Ile de France. Organization and function]. PMID- 2244270 TI - [Multiple trauma in children]. PMID- 2244271 TI - [Transportation in the immediate postoperative period]. PMID- 2244272 TI - [Nutrition of French adolescents. Current views]. PMID- 2244273 TI - [Vaccination in infants born to HIV seropositive mothers]. PMID- 2244274 TI - [Pediatric S.M.U.R. (Mobile Services for Emergencies and Resuscitation). Materials and means]. PMID- 2244275 TI - [Activities of pediatric S.M.U.R. (Mobile Services for Emergencies and Resuscitation)]. PMID- 2244276 TI - Biopsy of the breast for mammographically detected lesions. AB - We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001). PMID- 2244277 TI - Emergency portosystemic shunt in patients with variceal bleeding. AB - Thirty-five patients for whom emergency sclerotherapy or conservative treatment, or both, failed to arrest variceal bleeding, or who had early rebleeding and required emergency portosystemic shunts (EPSS) were studied. EPSS permanently controlled the variceal bleeding in all but one patient. In this patient, the shunt was patent as demonstrated by angiography. Esophageal varices disappeared in 18 patients and were reduced in 14. Three patients died before the endoscopic examination could be performed. The causes of death were hepatic failure in two and bleeding ulcerations of the gastric fundus in the other patient. One patient was classified in Child's category B and two in Child's category C. Thirty-two patients submitted to EPSS and were discharged alive. Twelve of these patients subsequently died, at an average of 11.2 months after undergoing the shunt procedure. Four of 12 patients died of hepatic failure; two patients died of hepatomas; two, other neoplasia; three, hemorrhaging duodenal ulcers, and one patient, renal failure. Analysis of actuarial survival rates showed that the five year survival rate was 43 per cent. The long term survival rates were fewer for patients with Child's category C than for those with combined Child's categories A and B (five year survival rates were 21 versus 55 per cent; p less than 0.05). During the follow-up period, none of the patients had variceal bleeding. Chronic encephalopathy developed in six, which was mild in three, moderate in one instance and severe in two. It developed soon after EPSS, with onset in the first month after discharge in three. Thus, when conservative treatment fails to arrest variceal bleeding, EPSS should be performed to guarantee definitive control of hemorrhage and prolong the survival period. PMID- 2244278 TI - Trends in conserving treatment of invasive carcinoma of the breast in females. AB - This population-based study presents trends in the treatment of node-negative invasive carcinoma of the breast in females during the 1980s in the Detroit metropolitan area. It was done to determine whether or not there has been a significant shift toward conservation of the breast from 1980 to 1987. Trend analyses of surgical treatment, tumor size, node status, year of diagnosis, age and race were performed for 13,217 patients drawn from the Metropolitan Detroit Cancer Surveillance System. A significant increase in the use of conserving the breast was observed, with younger women receiving this treatment option more often than older women. Implications for a continuing shift in the biologic findings and treatment of carcinoma of the breast are discussed. PMID- 2244279 TI - Correlation between hyperthermoradiosensitivity and clinical effect in carcinoma of the esophagus. AB - The correlation between hyperthermoradiosensitivity evaluated by an in vitro succinate dehydrogenase inhibition (SDI) test and the histopathologic effects of hyperthermochemoradiotherapy (HCR therapy) were investigated in 43 patients with carcinoma of the esophagus. The succinate dehydrogenase (SD) activity of tissue fragments taken at biopsy was assayed after exposure to heat (43 degrees C.) and radiation (6 grays) was done. The sensitivity to radiation plus heat treatment was estimated by the percentage of SD activity of the treated cells, compared with that of the control cells. The 43 patients were divided into three groups according to the degree of SD activity after exposure to radiation plus heat treatment. The SD activity was less than 50 per cent in group 1 (highly sensitive), between 50 and 70 per cent in group 2 (moderately sensitive), more than 70 per cent in group 3 (less sensitive). Eighteen of 20 in group 1, 11 of 17 in group 2 and two of six in group 3 were classified as being histopathologically "effective" for HCR therapy. The two year survival rate for groups 1, 2 and 3 were 55.5, 34.9 and zero per cent, respectively, while there were no statistical differences with regard to prognostic factors. These data suggest that in vitro activities of SD correlate well with the clinical effectiveness of HCR therapy. Therefore, it is recommended that a SD inhibition test be included among the guidelines for clinical management. PMID- 2244280 TI - Neoplastic changes in the stomach after gastrectomy. AB - Partial gastric resection for benign ulcer disease has been associated with an increased incidence of mucosal dysplasia and invasive adenocarcinoma, particularly 15 to 20 years after resection. These remnant carcinomas are particularly virulent with little hope of resection or cure once symptoms occur. Using a planned protocol of routine endoscopic surveillance with biopsy, the goal was to identify early markers of neoplasia, that is, dysplasia, and a diagnosis of adenocarcinoma of the gastric remnant, while both resection and cure were possible. Between July 1980 and August 1988, yearly flexible gastroscopic examination and random biopsy have been performed on 163 patients at least ten years after gastrectomy for benign ulcer disease. All biopsy results were interpreted for findings of dysplasia and early gastric adenocarcinoma. Results of this ongoing screening program revealed dysplasia of the gastric remnant in nine patients with eventual findings of adenocarcinoma in four of this group. These patients underwent total gastrectomy with findings of limited disease. Five patients with mucosal dysplasia continue to be observed at six month intervals. Three additional gastric carcinomas were found on initial gastroscopic screening, while one patient had adenocarcinoma diagnosed during a third yearly gastroscopic examination. These eight asymptomatic patients with adenocarcinoma in the gastric remnant had a postgastrectomy interval which ranged from 15 to 29 years (mean of 26.5 years). The results of this study support the concept of neoplastic change in the gastric remnant as a function of time from initial gastric resection. Findings of dysplasia on random biopsy indicate a greater likelihood of development of carcinoma of the gastric remnant and identify a subset of patients requiring aggressive endoscopic surveillance. PMID- 2244281 TI - The role of preoperative radionuclide ventriculography in defining outcome after revascularization of the extremity. AB - Revascularization of the extremity was performed upon 110 patients after preoperative radionuclide ventriculography (RNVG). Mean ejection fraction (EF) was 50 +/- 13 per cent. Ventricular wall motion abnormalities were present in 46 per cent. Revascularization included inflow procedures, such as aortofemoral (n = 25) or extraanatomic bypass (axillofemoral or femorofemoral, n = 11); infrainguinal reconstruction, including femoropopliteal or distal bypass (n = 43), and other procedures to improve perfusion of the limb or correct complications after previous vascular reconstruction upon the extremity (n = 31). Perioperative (30 days) mortality rate was 0.9 per cent and 97.0 per cent of the patients were discharged alive from the hospital. Myocardial infarction (MI) occurred in 3.6 per cent, new ventricular arrhythmia in 1.8 per cent and congestive heart failure in 6.4 per cent of the patients during the perioperative period. During follow-up study (607 +/- 363 days), 7.3 per cent required major amputation, ipsilateral to reconstruction, 5.5 per cent required surgical or angiographic revision for hemodynamic failure of the reconstruction prior to thrombosis and 12.7 per cent thrombosed part or all of the reconstruction. Revascularization failure did not appear to be related to the level of cardiac function. Those with normal (greater than 50 per cent) EF had greater over-all survival by life table analysis than those with EF less than or equal to 50 per cent (p = 0.0006, Mantel-Cox test). Ventricular wall motion abnormalities were associated with reduced over-all survival (p = 0.008, Mantel-Cox test). The presence of angina or previous MI, singularly or in combination, did not have an adverse effect on over-all survival, whereas diabetes (p = 0.0058, Mantel-Cox test) and cigarette smoking (p = 0.0137, Breslow test) were associated with significantly diminished over-all survival. Preoperative RNVG can identify subgroups at a survival disadvantage after revascularization of the extremity in a population in which the presence of angina or previous MI does not predict survival. PMID- 2244282 TI - Long term survival and severe rebleeding after variceal sclerotherapy. AB - Of 197 consecutive patients with cirrhosis admitted because of bleeding from esophageal varices, 133 were included in a prospective study of elective sclerotherapy. We evaluated the incidence of extensive rebleeding and mortality rate. The period of study was 54 months and the mean follow-up period was 21 months. Forty-one patients had severe rebleeding and a majority of the episodes occurred during the first year. Only four patients had more than five sessions of sclerosis when rebleeding occurred. The probability rate for patients to be free of severe rebleeding after 48 months, according to Pugh's classification, was 88 per cent for those with grade A, 50 percent for grade B and 43 percent for grade C. The over-all mortality rate was 38.8 per cent (53 patients), with the highest rate noted during the first year. The mortality rate of patients with severe rebleeding was much higher than that of those who did not rebleed. Kaplan-Meier survival analysis at four years was 52 per cent, and survival rates in relation to Pugh's classification were 73 per cent for A, 53 per cent for B and 34 per cent for C. Differences between the three groups were statistically significant. Therefore, because of the high mortality rate associated with patients with cirrhosis and extensive rebleeding during the first year, it is important to achieve, as soon as possible, eradication of esophageal varices. PMID- 2244283 TI - Bladder surface glycosaminoglycans is a human epithelial permeability barrier. AB - Transitional epithelium of the bladder has been known to be impermeable. The data reported herein suggest the principal barrier to permeability may be glycosaminoglycans (GAG) of the surface of the bladder. We examined the ability of surface GAG to prevent a small molecule, urea, from moving across the epithelium in humans. It appears that GAG provide a physical barrier which prevents small molecules from reaching the underlying tight junctions and cell membranes and, hence, are a major permeability barrier. Normal volunteers (27) had 100 milliliters of a 200 grams per liter urea solution placed into their bladders for 45 minutes. Net flow of urea from the bladder lumen was 5.1 per cent. Volunteers who were capable of completing the study (19) had protamine sulfate (5 milligrams per milliliter) instilled in the bladder for 15 minutes, then removed and a second urea study done. Urea loss was significantly higher at 22 per cent (p less than 0.02). A solution of heparin (2,000 units per milliliter) was instilled for 15 minutes followed by a third urea study and urea loss was reversed to 9 per cent. All volunteers experienced significant urinary urgency and discomfort after protamine treatment which were reduced by heparin. PMID- 2244284 TI - Carotid endarterectomy for chronic retinal ischemia. AB - Carotid arterial disease may result in a variety of ischemic ocular problems that can eventually lead to permanent blindness. From 1984 to 1988, 18 patients underwent reconstruction of the carotid artery in an attempt to restore normal retinal arterial flow and, thereby, reverse or prevent progression of ischemic oculopathy. During a mean period of 21 months after carotid arterial reconstruction, subjective improvement in vision as well as a resolution in eye and periorbital pain was reported in 87.5 per cent of the patients. Measured visual acuity improved or stabilized in 94.4 per cent; macular photostress recovery times improved in 87.5 per cent, funduscopic examinations noted improvement or resolution in ischemic signs in 93.3 per cent and intraocular pressures improved in two of three patients. One patient experienced recurrent episodes of amaurosis fugax, which resolved after two weeks and did not recur. A second patient experienced an increase in intraocular pressures with visual deterioration, required laser photocoagulation after which the condition of the patient stabilized but only after significant visual impairment. Carotid arterial reconstruction is effective for the treatment of ischemic oculopathy and is most beneficial if performed early, before the onset of irreversible neovascular glaucoma. PMID- 2244285 TI - Therapeutic dilemmas associated with antenatally detected ovarian cysts. AB - Fifteen instances of ovarian cysts detected antenatally are reported. Seven cysts more than 5 centimeters in diameter were treated surgically because of clinical signs, such as palpable abdominal mass, vomiting and abdominal distension. Seven cysts less than 5 centimeters in diameter, and one cyst more than 5 centimeters in diameter began to regress spontaneously within six months after birth. Because the pathophysiologic nature of neonatal ovarian cysts has not been elucidated and because the borderline between physiologic and pathologic factors is still unclear, we propose a more conservative approach in the management of neonatal ovarian cysts to avoid unnecessary operations. PMID- 2244286 TI - Simplified technique for control of femoral arterial bleeding after coronary angioplasty. AB - A method of achieving arterial control by inserting an embolectomy catheter through the femoral introducer sheath in the patient with femoral arterial bleeding after PTCA is described herein. This approach allows quick control with less dissection and negligible blood loss. PMID- 2244287 TI - Intraluminal anastomosis of the biliary and pancreatic ducts to a Roux-en-Y loop of the jejunum. PMID- 2244288 TI - Intraoperative pressure profile measurement and continence mechanism adjustment in the Indiana pouch urinary reservoir. AB - We have described herein a simple pressure transducer system which helps the surgeon to tailor suture placement and achieve a continent ileocecal reservoir. It seems that fewer Lembert sutures than previously recommended are necessary to create a continent reservoir, although further study is needed. PMID- 2244289 TI - The hazards of surgical glove dusting powders. AB - Surgical contaminants of many kinds, including glove powder, constitute a source of formation of granulomas. This is particularly well-documented in the peritoneal cavity ("starch peritonitis"), but has been documented in most anatomic sites. The production of starch-free gloves should remove this hazard, but the surgeon should remain aware that most particulate substances introduced into the body inevitably set up an inflammatory response. PMID- 2244290 TI - Gallstones, cholecystitis and diabetes. AB - Findings from studies showing an increased incidence of gallstones in diabetic patients do not control for other variables, such as obesity. There is no proof that diabetic patients have more gallstones. Gallstones do not cause diabetes mellitus. The principal gallbladder pathologic feature in diabetic patients is a functional deficit of uncertain etiologic factors, creating a large, flaccid, poorly emptying organ. Bile acid and lipid composition are usually increased in diabetic patients. Cholecystitis seems to be a more serious disease in diabetic patients, with worse infectious sequelae and more rapid disease progression. This conclusion has not been examined statistically. Even with modern care, the complication rate for operations upon the biliary tract in patients with diabetes is increased. Those with diabetes are generally older than other patients requiring cholecystectomy. Systemic changes of aging partly explain increased morbidity and mortality. Diabetic patients with symptomatic gallbladder disease usually require operation. Risk of cholecystectomy in diabetic patients is similar to that in nondiabetics. Prophylactic cholecystectomy for diabetic patients with "silent" gallstones was formerly recommended because of an apparent high risk of cholecystitis. Until the natural history of gallstones in those with diabetes has been defined, such patients should be considered in danger of serious illness. The risk of acute cholecystitis in diabetic patients with stones is probably significant enough to warrant the performance of early cholecystectomy. PMID- 2244291 TI - How and why aztreonam works. AB - Aztreonam is the first monocyclic beta-lactam antibiotic (monobactam) to be tested clinically. Its synthetic structure determines specific areas of activity, including enhanced activity against Pseudomonas species, exceptional activity against gram-negative bacteria, stability to beta-lactamases and lack of activity against gram-positive bacteria--all of which can be directly related to its chemical composition. Aztreonam has a high affinity for the protein-binding protein 3 (PBP-3) of aerobic gram-negative bacteria. Most of these organisms are inhibited and killed at low concentrations of the drug. Aztreonam binds poorly to PBP sites of the aerobic gram-positive and anaerobic bacteria and consequently has relatively poor inhibitory effects against these bacteria. In vitro, minimum inhibition concentration (MIC) values against almost all of the Enterobacteriaceae and against Neisseria and Haemophilus strains are typically below 1 microgram per milliliter. MIC values against Pseudomonas aeruginosa of 8 micrograms per milliliter are comparable with those of other antipseudomonal beta lactams and the acylureidopenicillins. As combination therapy with amino glycosides, aztreonam acts in synergy against P. aeruginosa, Acinetobacter and gentamicin-resistant gram-negative rods. Aztreonam is widely distributed in the body tissues and fluids, and the average elimination half-life is 1.7 hours. Intramuscular dosing results in peak serum levels in approximately one hour, while intravenous dosing results in peak levels within five minutes. After a 2 gram dose given intravenously, MIC90 values for most of the Enterobacteriaceae are exceeded for eight hours, and those for P. aeruginosa, for almost six hours. The steady-state volume of distribution is approximately 0.18 liter per kilogram. Concentrations above the MIC90 for most gram-negative bacteria are also present within bone, prostate and cerebrospinal fluid. Between 60 and 70 per cent of the drug is excreted unchanged in the urine, resulting in concentrations approximating 3,000 micrograms per milliliter two hours after a 1 gram dose given intravenously. Serum clearance of aztreonam is directly proportional to creatinine clearance. Dosage adjustment must, therefore, be made in the presence of reduced clearance. Dosing varies between 0.5 and 2.0 grams every six to 12 hours, depending on the severity of the infection. The characteristics of aztreonam suggest that it is a useful nonnephrotoxic drug for treatment of aerobic gram-negative infection. PMID- 2244292 TI - Aminoglycosides: assessing the potential for nephrotoxicity. AB - Although aminoglycosides have been a mainstay of antibiotic therapy in postsurgical infections, certain patients may be at risk for potential aminoglycoside induced toxicities. Aminoglycoside nephrotoxicity is one of the most frequent causes of iatrogenic renal failure. A narrow toxicity to therapeutic ratio, a relatively long serum half-life and concentration in the renal cortex all contribute to renal dysfunction. Patients at greatest risk for aminoglycoside-induced nephrotoxicity include the elderly, patients with pre existing renal disease and those who are volume depleted. Calculations based on the results of a multicenter study demonstrate that the average additional cost incurred for each patient who had aminoglycoside-related nephrotoxicity was $2,501. Methods are reviewed for prospectively assessing the potential for development of nephrotoxicity to identify patients for whom effective therapeutic substitutes for aminoglycosides should be sought. PMID- 2244293 TI - Pathogenesis and treatment of intra-abdominal infection. AB - Intra-abdominal infection is considered potentially life-threatening. Such infection is frequently secondary to perforated viscera, trauma or inflammatory disease. Simple abscesses may be drained percutaneously with roentgenologic guidance; complex abscesses often require open surgical drainage. Secondary peritonitis is usually polymicrobial; broad-spectrum antimicrobial therapy effective against aerobic and anaerobic gram-negative bacteria, as well as gram positive organisms, is essential. Newer antibiotics, administered either singly or in combination, have been used successfully to treat intra-abdominal infection while avoiding the toxicity of aminoglycosides. PMID- 2244294 TI - Diagnosis and treatment of pneumonia in the surgical intensive care unit. AB - It is often difficult to detect the onset of parenchymal pulmonary infection (pneumonia) in a surgical intensive care unit (SICU) setting. Clinical and laboratory parameters that usually indicate the presence of pneumonia, such as fever, elevated white blood cell count and abnormal sputum culture, may also be present in patients with nonpneumonic infection. Prompt diagnosis is particularly important for patients in SICU because the mortality rate associated with pneumonia in these patients may be as high as 50 per cent. In the SICU setting, pneumonia is best diagnosed using well-defined roentgenologic criteria. Treatment should consist of a broad-spectrum antibiotic regimen to which all sputum pathogens are sensitive. Such a regimen significantly reduces the mortality rate for patients with pneumonia in an SICU setting. Aztreonam has been found to be as effective against susceptible gram-negative bacilli as traditional agents, such as the aminoglycosides, and to have a significantly milder side effect profile. PMID- 2244295 TI - Antifungal therapy and its use in surgical treatment. AB - Modern surgery continues to make significant therapeutic advances, and a major component in the adjunctive care allowing these improved procedures is the successful use of broad-spectrum antibacterials. However, the widespread administration of potent antibacterials and the frequent use of a variety of catheters, along with an increase in the number of immune compromised patients requiring invasive procedures, have allowed deep-seated mycoses to become more common. Nosocomial fungal infections are frequent, particularly in the urinary tract and in the blood. This rise in identified fungal infections, along with frequent empiric treatment of suspected infection, has significantly increased amphotericin B therapy in surgical services in the last five years. While amphotericin B remains the standard for treatment of nosocomial mycoses, other antifungal agents are available (flucytosine, miconazole, ketoconazole and fluconazole). Despite experience with the older agents and the development of new agents, many questions remain concerning the use of currently available antifungal treatments in postsurgical patients. The following discussion attempts to summarize the magnitude of the problem, the difficulties with diagnosis and laboratory evaluations, the characteristics of the antifungal agents and particular problems with antifungal treatment in surgery. PMID- 2244296 TI - Surgery-related infections: a challenge for the physician. Introduction. PMID- 2244297 TI - Neurosurgery in Saudi Arabia. PMID- 2244298 TI - Autopsy study of unruptured incidental intracranial aneurysms. AB - The autopsy files and preparations of unruptured incidental intracranial aneurysms seen at the Montefiore Medical Center between 1951 and 1987 were reviewed. There were 84 patients with 102 unruptured aneurysms in a total of 10,259 autopsies, giving a prevalence of 0.8%. Sixteen of the 84 (19%) had multiple aneurysms. The thickness of walls of aneurysms could be estimated in 78 of 102 aneurysms, and was determined to be either thin or thin and thick in 71 aneurysms. In this study, four noteworthy factors were found: (1) the incidence of unruptured aneurysms was higher in elderly patients aged 60 years or older, and the peak percentage was 1.2% in the seventh decade; (2) aneurysms occurred more frequently in females than males, with a ratio of 53:31; (3) the most common site of aneurysms was the middle cerebral artery; 37 of 102 aneurysms (36%) occurred on it; and (4) the rate of small aneurysms was very high; 50 of 93 aneurysms (54%) were 4 mm or less in diameter, and 33 aneurysms (35%) were 5-9 mm in diameter. However, relationships could not be found between age distribution and location, size, or thickness of walls; between gender and size or thickness of walls; between location and size or thickness of walls; or between size and thickness of walls. Based on published statistics on subarachnoid hemorrhage and this study, the rupture rate of unruptured aneurysms seems to be very low. Although the risk of rupture may be relatively low in small aneurysms, its low risk probably cannot be explained adequately by morphological examination only. PMID- 2244299 TI - Vancomycin pharmacokinetics in hydrocephalic shunt prophylaxis and relationship to ventricular volume. AB - Vancomycin pharmacokinetics were determined in 25 patients receiving ventriculoperitoneal shunts for hydrocephalus. Computed tomography scan-derived ventricular-brain ratio as an expression of hydrocephalus varied between 9.3% and 15.4% (12.9% +/- 1.7%). One hour prior to surgery each patient received 1 g of vancomycin infused intravenously over 60 minutes. Samples of cerebrospinal fluid and venous blood were obtained 1 hour later and vancomycin levels assayed by fluorescence polarization immunoassay. There were 11 females and 14 males, with a mean age of 44.5 +/- 10.3 years and a mean weight of 72.0 +/- 11.4 kg. All had normal renal function. Levels of vancomycin in the cerebrospinal fluid at 1 hour ranged from 0.1 to 1.5 micrograms/mL (0.9 +/- 0.3). Weight did not affect these values (p greater than 0.1). Simultaneous blood vancomycin levels varied between 9.1 and 38.7 micrograms/mL (22.3 +/- 8.3). Ventricular volume, expressed as the ventricular-brain ratio, did not correlate with cerebrospinal fluid vancomycin levels (p greater than 0.5). There was no significant increase in concentrations of vancomycin in CSF as cerebrospinal fluid protein concentration increased, nor when blood vancomycin concentration was greater than 20 mg/dL (therapeutic range) (p greater than 0.1). No patient had evidence of infection at 6 months follow up. These results indicate minimal cerebrospinal fluid penetrance of vancomycin when administered systemically 1 hour prior to shunt surgery. In addition concentrations of vancomycin in cerebrospinal fluid bear no relationship to weight, ventricular volume, meningeal inflammation, or blood levels in the therapeutic range. The minimum inhibitory concentration of vancomycin for staphylococci is 1.5 to 3.1, and as bactericidal levels of 5 to 8 minimum inhibitory concentration are needed to kill organisms, a combination of both systemic and intraventricular vancomycin may be needed to ensure adequate cerebrospinal fluid and tissue concentration of antibiotic during shunt prophylaxis. PMID- 2244300 TI - Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery in hydrocephalus before and after treatment. AB - We studied Pourcelot's index (PI), which shows cerebral vascular resistance, in the anterior cerebral arteries and basilar artery, and the PI ratio (Pourcelot's index in the anterior cerebral artery/Pourcelot's index in the basilar artery) in 11 measurements of hydrocephalus. The mean values of PI in the anterior cerebral artery, basilar artery, and the PI ratio before treatment were significantly higher than those after treatment and those in normal infants. Before treatment, the mean PI in the anterior cerebral arteries was significantly higher than the mean PI in the basilar artery. All PI ratios increased to 1.00 or more. After treatment and in normal infants, the mean PI in the anterior cerebral arteries was significantly lower than the mean PI in the basilar artery. All PI ratios decreased to less than 1.00. We believe that the PI ratio is useful to evaluate the need or effect of treatment in hydrocephalus. PMID- 2244301 TI - Magnetic resonance imaging of experimental rat brain tumors: histopathological evaluation. AB - Using RG-C6 glioma-transplanted rats, we studied precontrast and postcontrast magnetic resonance imaging, extravasation of Evans blue, and histology. In all rats, tumor was enhanced with gadolinium-diethylenetriaminepentaacetic acid (Gd DTPA). The necrotic portion in the tumor, however, was not enhanced. Hemorrhage and hydrocephalus were clearly visualized on both the precontrast and postcontrast images. Blood-brain barrier-disrupted areas stained with Evans blue and areas enhanced with Gd-DTPA on magnetic resonance imaging were nearly consistent. It is suggested that the mechanism of brain tumor enhancement with Gd DTPA on magnetic resonance imaging is simply related to the degree of alteration of the blood-brain barrier. The Gd-DTPA-enhanced magnetic resonance imaging, even with low magnetic field, is useful for the evaluation of size, shape, and location of experimental rat brain tumors. PMID- 2244302 TI - Brain stem tuberculoma in adult patients: diagnosis and treatment. AB - A consecutive series of six adult patients ranging in age from 29 to 53 years is presented. The clinical and radiological features in each patient are described. Attention is drawn to the features demonstrated on computed axial tomography. In only one patient, the first encountered, was surgical excision undertaken and histological verification obtained. One patient died before any form of treatment could be instituted. The remaining four patients were treated with antituberculous chemotherapy alone and their progress monitored by sequential computed tomography. The excellent response and good outcome in this conservatively treated group are documented. PMID- 2244303 TI - Regional ischemia in cerebral venous hypertension due to embolic occlusion of the superior sagittal sinus in the rat. AB - To determine the pathophysiological changes in brain tissue that characterize damage following cerebral venous hypertension, a model of cerebral venous hypertension in the rat was devised. This experimental model has the advantage of simultaneously measuring the regional changes in cerebral blood flow as well as the metabolism. The ischemic area demonstrated by the accumulation of NADH is confined to the cerebral cortex and becomes enlarged in proportion to the increase in venous pressure. This metabolic disturbance appears even in the very early period following cerebral venous hypertension. These pathophysiological features are different from those observed in the case of intracranial hypertension. PMID- 2244304 TI - Cerebral hemodynamics in patients with normal pressure hydrocephalus: correlation between cerebral circulation time and dementia. AB - Regional cerebral blood flow and regional cerebral circulation time were measured in 13 demented patients with chronic hydrocephalus, mostly normal pressure hydrocephalus. The average hemispheric, frontal, and temporal cerebral blood flows were significantly reduced. The average regional cerebral circulation time values were significantly prolonged in the frontal, temporal, and thalamic regions, most markedly in the frontal white matter, where periventricular lucency was observed on computed tomography. Clinical improvement was obtained in all patients after operation. While postoperative regional cerebral blood flow values did not change compared with preoperative ones, postoperative regional cerebral circulation time values were significantly reduced in all the regions measured, and most markedly in the frontal white matter. The present results suggest that microcirculation in the frontal lobe is closely correlated with dementia in association with pressure exerted on the nerve fibers in the frontal white matter in patients with normal pressure hydrocephalus. PMID- 2244305 TI - Effects of 1.32-micron Nd-YAG laser on brain thermal and histological experimental data. AB - Considering that the 1.32-microns Nd-YAG laser should have physicothermal properties close to those of the CO2 laser, a series of experiments were conducted on rat cortex (N = 51). Three laser wavelengths were compared: CO2 laser (10.6 microns), 1.06-microns Nd-YAG, and 1.32-microns Nd-YAG lasers. For each shot, temperature measurements were recorded with an infrared thermographic videocamera. The digitized signals were figured as thermal profiles and temperature developments. Ninety-five shots were correctly studied and analyzed: CO2, N = 29; 1.06-microns Nd-YAG, N = 20; 1.32-microns Nd-YAG, N = 46. The histological lesions produced by these three lasers were compared on animals killed 24 hours (N = 20), 8 days (N = 20), and 30 days (N = 5) after the laser impacts. For equivalent densities of energy, the depth of cortical necrosis was comparable for the CO2 laser (200-250 microns) and the 1.32-microns Nd-YAG laser (210-260 microns) whatever the date of death; the 1.06-microns Nd-YAG laser shots were responsible for much more important damage (400-550 microns). Because of its important absorption in water and nervous tissue, the authors consider the 1.32 microns Nd-YAG laser most suitable for neurosurgery, particularly because it is conducted through optic fibers, and therefore is easy to handle during neurosurgical procedures. PMID- 2244306 TI - Third ventricle cavernous angioma: report of two cases. AB - Cavernous angioma arising in the third ventricle is an extremely rare disease. We have reviewed five cases previously reported, as well as our own two cases, and discuss the clinical characteristics of and surgical approach to cavernous angioma at this site. The bifrontal craniotomy and interhemispheric translamina terminalis approach minimize the damage to the brain and allow for an approach to the third ventricle in a wide operative field with minimal compression of the brain itself. We have found this approach to be suitable for surgery on angiomas of the anterior half of the third ventricle. PMID- 2244307 TI - Magnetic resonance imaging of vertebral osteoblastoma: a report of two cases. AB - Two patients with vertebral osteoblastoma evaluated with computed tomography and magnetic resonance imaging are presented. A literature review revealed that cases of osteoblastoma originating within the vertebral body are exceedingly rare. PMID- 2244308 TI - Arteriovenous malformation at the cervicomedullary junction: a case report with magnetic resonance imaging. AB - A rare case of arteriovenous malformation at the cervicomedullary junction is reported. A 72-year-old man developed symptoms of total transection of the upper cervical cord without evidence of subarachnoid hemorrhage. The arteriovenous malformation had an intramedullary nidus with an aneurysmal dilatation at the C-1 level. This lesion was diagnosed by magnetic resonance imaging and confirmed at autopsy. The neurological symptoms may have been due to compression of the spinal cord by the intramedullary lesion, followed by degeneration and necrosis. The usefulness of magnetic resonance imaging in the neuroradiological diagnosis is particularly emphasized. PMID- 2244309 TI - Spinal synovial cyst: case report using magnetic resonance imaging. AB - The case of a 65-year-old woman who developed a spinal synovial cyst at the L4-5 disk space is reported. Her clinical signs and symptoms are presented. A comparison among her preoperative myelogram, computed tomography scan, and magnetic resonance imaging showed magnetic resonance imaging to be more accurate in detailing both the intraoperative and pathological findings. PMID- 2244310 TI - Aqueductal (pencil) glioma presenting as neurogenic pulmonary edema: a case report. AB - A case of neurogenic pulmonary edema due to hydrocephalus, without initial neurological deficit, is described. Computed tomography demonstrated a ring enhancing lesion in the tectum of the mesencephalon obstructing the aqueduct of Sylvius. The lesion, on autopsy, was a rare mesencephalic glioma described in the literature as a "pencil glioma" of the aqueduct. PMID- 2244311 TI - Brain abscess associated with congenital pulmonary arteriovenous fistula. AB - A case of brain abscess associated with congenital pulmonary arteriovenous fistula was presented and 52 reported cases were reviewed. The brain abscess was successfully treated with repeated aspiration and drainage, and the pulmonary arteriovenous fistula, located in the right lower lobe, was resected. The arteriovenous fistula occurs as a common pulmonary manifestation of hereditary hemorrhagic telangiectasia; however, no symptoms suggesting these two were noted in this case. Brain abscesses can be an initial clinical manifestation in asymptomatic pulmonary arteriovenous fistula. This possible association should be borne in mind in cases of brain abscesses of unexplained etiology. PMID- 2244312 TI - A near miss--Osler's early description of Cushing's syndrome with, regrettably, no post-mortem examination. 1898. PMID- 2244313 TI - [Where does the water drain, as it leaves the dental clinic?]. PMID- 2244314 TI - [Mercury in waste water from dental clinics]. PMID- 2244315 TI - [Facts, myths and future perspectives regarding amalgam., mercury and resins]. PMID- 2244316 TI - [Lead foil artifacts as a result of unintentional bending of dental X-ray films]. AB - The lead foil of dental x-ray film packets may cause a number of artifacts; especially well known are the "tractor treads" and "herringbone patterns" following a backward filmpositioning in the patient's mouth. In the present paper a specific and seldomly occurring lead foil artifact is described which is caused by bending of the film packet. Four cases collected over a 5-year period are presented. Although different the four cases show a number of similarities. They appear as radiopaque areas covering the upper or lower halves of the films. Their borders show the characteristic "sandbar-pattern" previously described by the author. The explanation of their origin is that the patient has been occluding on a part of the film packet which has been bent to a nearly horizontal position. The x-rays directed against the edge of the lead foil will be absorbed causing irregular radiopaque areas on the film lined by "sandbar-pattern". When the film packet is bent, the lead foil will be stretched and drawn a little away from the edges of the films. Consequently the x-rays will be able to expose the edges of the films. Irregularities of the foil will give rise to concentric "bars". The lead foil is only of limited radiopacity, but due to the oblique direction of the x-rays through the foil the absorbing effect is intensified. PMID- 2244317 TI - [Toxin effects from chlorhexidine gluconate: case report]. AB - A patient with side effect of chlorhexidine gluconate is presented. The patient showed major changes of the oral mucosa after extreme overdosage of mouthrinsing with chlorhexidine gluconate. The changes were different from other known mucosal lesions, as the patient showed thickening of the mucosa, clinical resembling leukoplakia. The changes disappeared after decreasing the dosage of the drug. PMID- 2244318 TI - [Unusual case involving a toothache]. PMID- 2244319 TI - [Consumers view of treatment by dental hygienists in private practice]. AB - Questionnaires were sent to 22 dental practitioners. Each dentist was sent two types of questionnaires, one to be completed by the hygienist and the other one by the patients. The sampling was done by selecting at random approximately every sixth clinic employing a dental hygienist. Of 1100 questionnaires 710 were completed and returned. The investigation illustrates the patients opinion on different aspects of the dental hygienist's technical and social skills and of the cost of care. There was an overwhelming consumer satisfaction regarding the quality, as well as the cost, of dental care performed by a hygienist. Therefore, a broad use of well qualified dental hygienists as an auxilliary to a dentist is one way to lower the cost of dental health care in the future. PMID- 2244320 TI - [Hygiene in dental practice]. PMID- 2244321 TI - [Multiple cysts of the maxilla and mandible. Nevoid basal cell carcinoma syndrome -Gorlin's syndrome]. PMID- 2244322 TI - [Case of patients with occlusal disharmony in a Swedish district. Attitudes and needs]. PMID- 2244324 TI - Leadership and followership. PMID- 2244323 TI - [Dental care of the future demands high quality radiographic diagnosis]. PMID- 2244325 TI - What a nurse can do to improve patient meds compliance. PMID- 2244326 TI - [Role of the practicing physician in prevention]. PMID- 2244327 TI - [From theory to practice: on the history of cardiovascular epidemiology]. AB - The road of research from analytical epidemiology which led to the description of coronary heart disease risk factors, to experimental epidemiology (intervention studies) which brought evidence for the effectiveness of prevention through risk factor reduction, is delineated in historical sequence. This knowledge serves as the basis for the two strategies of preventive cardiology: the individual (high risk) and the population strategy; the first is mainly in the domain of the practicing physician while the second requires his support within the framework of health planning in the community. PMID- 2244328 TI - [Smoking cessation in general practice]. AB - Health problems and diseases related to smoking are common problems in primary health care. However, primary health care physicians are less inclined to advise their smoking patients to stop smoking and give specific counselling. This is in contrast with the expectations of the smoking patients who expect their physicians to do so. An introduction to behavior modification for smoking cessation in primary health care is given. Factors linked to successful cessation are shown, as indication for nicotine substitution in the weaning stage is discussed. Stop smoking counselling is a challenging task in primary health care, its efficacy being often underestimated by the physician. PMID- 2244329 TI - [Alcoholism and the practicing physician]. AB - Alcoholism is a major public health problem in Switzerland as in most Western industrialized countries. The general practitioner should be a key person in screening for alcohol abuse and dependency. Yet, the general practitioner should provide information and counselling upon the consequences of excessive alcohol consumption. In a strategy of routine screening by general practitioners, asking the patient about the quantity and the frequency of alcohol consumption, clinical examination and laboratory testing are less effective than a standardized questionnaire. Examples of questionnaires include the Michigan Alcoholism Screening Test (MAST) and the CAGE questionnaire. The rationale for systematic screening is that early pathological injuries due to excessive alcohol consumption are reversible. Yet, the prognosis seems to be more favourable where therapy begins early and the amount of psychosocial problems is limited. An early therapeutic intervention could be started as a multidisciplinary approach, targeting the patient and emphasizing the role of the patient's physician. PMID- 2244330 TI - [Omega-3-fatty acids: their value in nutrition and prevention]. AB - Based on epidemiological, experimental and physiological evidence, this review examines whether omega-3 fatty acids (omega-3-PUFA) are cardioprotective and whether they are therefore relevant to the primary prevention of cardiovascular diseases. The high intake of omega-3-PUFA among Greenlandic Eskimos has been supposed to be a key factor for their low mortality rate of coronary heart disease (CHD). Other ecological studies from Norway and Japan suggest that higher fish consumption might be cardioprotective. Three cohort studies have shown an unequivocal inverse relation between fish-intake and CHD mortality, while two others--possibly for methodological reasons--have not shown clear overall associations. Several biological effects of omega-3-PUFA are known which may moderate and influence positively the pathogenesis of atherosclerosis. However, double-blind trials with clinical endpoints are not yet available to confirm these effects. For the time being, fish oil capsules should not be recommended as cardioprotective dietary supplementation, because some uncertainty about their long-term safety and dosage remains. Fish consumption is safe and modifies the FA pattern of the diet favourably. From the point of view of prevention, rising fish intake up to twice or three times weekly can therefore be recommended for people residing in Switzerland. PMID- 2244331 TI - [Hypercholesterolemia in general practice--2 representative surveys in Switzerland]. AB - Two representative surveys of general practitioners in 1987 and 1989 showed, that cigarette smoking and high blood pressure are considered the most important risk factors for coronary heart disease. Elevated blood cholesterol level rank third. Between the two surveys no significant changes took place. The blood cholesterol level is usually measured at a check-up visit or in presence of another risk factor. Routine measurement is not common. At what level do Swiss physicians initiate a therapy? The median range in 1989 for a diet therapy was 6.2-6.7 mmol/l (240-260 mg%) for a 30 years old person, and 6.7-7.2 mmol/l for a 60 years old person. Lipid-lowering drugs are used at about 1 mmol/l (40 mg%) higher levels and there is less agreement between the physicians. Within two years the levels of initiating therapy decreased significantly. Differences between the three Swiss language regions (german/french/italian) in initiating therapy can be seen. 90% of the physicians mentioned compliance problems with a diet therapy. In 1989 half of the surveyed doctors experienced insufficient results in both diet and drug treatment. Further, compliance problems and side effects of drug treatment are mentioned. Half of the physicians reported having tested their own cholesterol level in the last 12 months. Older physicians are considerably more conscious of high cholesterol levels than younger. PMID- 2244332 TI - [AIDS counseling in general practice]. AB - General practitioners are in prime position for promoting primary, secondary and tertiary HIV prevention. Counselling is an integral part of their work and a key step towards behavioural change of their patients. Particular attention must be given to counselling before and after the HIV antibody test. So far, the extraordinary potential of general practitioners to educate patients about HIV infection has been used insufficiently. The primary barriers to providing health education are lack of knowledge and discomfort with initiating discussions of sexuality or drugs use rather than lack of time or 'other health priorities', etc. These findings show the need to implement education programmes for physicians and other members of their medical practice. Additionally, patients should be encouraged to take the initiative in starting discussions about HIV. In Switzerland, an education programme for physicians is currently under way. PMID- 2244334 TI - [Prevention in general practice--results of a study of ambulatory health care in the Waadt and Freiburg cantons]. AB - Data on medical consultations were collected from a representative sample of self employed physicians showing that prevention activities comprised only a small proportion of ambulatory medical care. Preventive acts are more frequent among pediatricians and gynecologists, however. The current health system favours therapeutic aspects of medicine over preventive aspects: Lack of adequate training of physicians and modes of payment for medical acts tend to discourage prevention by doctors. PMID- 2244333 TI - [Air pollution--consequences for the general practitioner]. AB - Air pollution can also be considered a health risk for those living in Switzerland. During short episodes of high pollution (smog), protection from exposure can be recommended. The continuous air pollution problem, however, implies for the physician a complex educational task with regard to his patients. As the patient does not perceive a direct improvement in his personal health, it is difficult to promote ecologically acceptable behaviour. In view of the long term effects of continuous exposure to air pollution on the health of the population, such preventative activity is considered necessary. PMID- 2244335 TI - Effect of perinatal lead exposure on morphine tolerance in the neonatal rat. AB - Administration of lead (at 300 and 1000 ppm) in the maternal drinking water from conception to postnatal day 10 increased the sensitivity of 10-day rat pups to noxious stimuli and disrupted the dose-response relationship to morphine antinociception. Lead-exposed rats could be made tolerant to morphine over a 5 day period (twice daily injections of 5 mg/kg morphine, postnatal days 5-10) and antinociceptive responses in tolerant rats were also disrupted by lead exposure. PMID- 2244336 TI - Cytotoxicity induced by papaverine hydrochloride in fungal cell systems. AB - Cunninghamella echinulata was used to assess the cytotoxicity of papaverine (papaver), at concentrations ranging from 1 x 10(-5) to 1 x 10(-3) M for 1-6 days. Leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and changes in alkaline phosphatase (AP) activity and lactate/pyruvate (L/P) ratios were used as indices of cytotoxicity. Leakage of LDH occurred at the 6th day with 1 x 10(-3) M; AP activity and L/P ratios decreased after 6 days treatment with 1 x 10(-4) M, after 1 day with 1 x 10(-3) M, and after 3 days with 1 x 10(-4) M, respectively. This study provides support for the use of fungal cell systems to evaluate the toxicity of drugs and chemicals. PMID- 2244337 TI - The production of alveolar macrophage-derived growth-regulating proteins in response to lung injury. AB - Tissue injury elicits an inflammatory response, one element of which is the activation of the local macrophage population. Macrophages are recognized as the source of multiple growth-regulating proteins, and are thus thought to play an important role in wound healing. Injury to the lung by exposure to oxidant gases, particulates, chemicals or drugs is often followed by replication of the cells of the alveoli. The growth-regulating proteins released by alveolar macrophages (AM) may be one mechanism which controls the proliferation of these cells. This article describes the AM growth factors, the cell types which they affect, and the injuries known to cause their release. In view of the multiplicity and overlapping functions of the macrophage growth factors, potential mechanisms which might regulate the growth response of the surrounding cells are also considered. PMID- 2244338 TI - Effects of soman on calcium influx into rabbit aorta. AB - The acute addition of 10 microM soman to rabbit aorta rings did not increase resting 45Ca2+ influx significantly in the absence or presence of 10 microM norepinephrine or 80 mM potassium (P greater than 0.05). However, agonist-induced 45Ca2+ influx into aorta rings from rabbits that received soman daily for 7 days was significantly reduced (P less than 0.05) compared to agonist-induced influx into rings from control rabbits. The resting influx of 45Ca2+ into aorta rings from 7 day soman-treated and control rabbits was not different (P greater than 0.05). The depression by soman of norepinephrine- and K(+)-induced 45Ca2+ influx may be due to adaptive changes resulting from the 7-day administration of soman. PMID- 2244339 TI - Perfluoro-N-decanoic acid effects on enzymes of fatty acid metabolism. AB - In vitro perfluorodecanoate (PFDA) effects on Pseudomonas acyl-CoA synthetase, Candida acyl-CoA oxidase and pigeon muscle carnitine acetyltransferase were examined. Synthetase made little PFDA-CoA from PFDA. It used palmitate, oleate, laurate and decanoate more extensively. PFDA inhibited acyl-CoA formation from these acids. Palmitoyl-CoA formation was affected most. That of decanoyl-CoA was affected least. Inhibitions appeared to be competitive. Acyl-CoA oxidase test substrates were palmitoyl-CoA, lauroyl-CoA and decanoyl-CoA. Oxidase preferred C 10 and C-12 acyl-CoAs. PFDA inhibited oxidation of C-10 and C-12 acyl-CoAs more than that of palmitoyl-CoA. Inhibitions with C-16 and C-10 acyl-CoAs were competitive, KIs 593 +/- 150 and 76 +/- 6.0 microM. Acetyl-CoA was the best acetyltransferase substrate. C-2 to C-8 transfer from acyl-CoAs was inhibited similarly by PFDA. Inhibitions of C-2 and C-8 transfer were competitive and non competitive, respectively, KIs 111 +/- 15 and 76 +/- 28 microM. PMID- 2244340 TI - Hepatic and muscle injuries in mice treated with heptachlor. AB - Heptachlor is a major component of the insecticide, chlordane. It is a health hazard but is still in use in some countries of Southeast Asia. To elucidate the toxicity of heptachlor its effects on mice after oral and intraperitoneal administration were studied. A 3-day group, 92-day group and 180-day group were given heptachlor intraperitoneally, orally and ad libitum, respectively. Results showed increased levels of serum alanine aminotransferase and decreased levels of serum cholinesterase activity. Serum creatine phosphokinase levels increased significantly. These may be due to the disruption of muscle membrane by chlordane. Results also showed significant variations of serum lipid levels from control as heptachlor has a known effect on lipid metabolism. Also the lipid peroxide levels expressed as TBA values were increased significantly, showing heptachlor's role in causing liver injury. These results suggest that the deterioration of membranes due to lipid peroxidation leads to liver and muscle injuries caused by heptachlor. PMID- 2244341 TI - Teratological assessment of the antiprotozoal, diminazene diaceturate, in rats. AB - Diminazene diaceturate was dissolved in deionized water and administered to pregnant rats by oral gavage once daily on days 8-15 of pregnancy at dose levels of 0, 100, 250, 500 and 1000 mg/kg. On day 21 of pregnancy, the dams were killed and the number of implants, resorptions and live fetuses counted. All fetuses were examined by routine teratological method. A significant increase in fetal resorptions and decrease in fetal body weights were found at the 1000 mg/kg dose. No significant increase in the incidence of anomalous fetuses was observed in external, skeletal and internal examinations even at the maternally toxic dose of 1000 mg/kg. Thus, these data indicate that diminazene diaceturate is not teratogenic in rats. PMID- 2244342 TI - Arylamine N-acetyltransferase activities in cell lines of mouse, rat, hamster and man differing in their sensitivity to 1,6-dinitropyrene. AB - This study was aimed at monitoring N-acetyltransferase activities of continuous cell lines, which differ in their sensitivity to the toxic effects of nitroaromatic compounds. Transferase activities were measured toward the acetyl acceptors sulfamethazine and p-aminobenzoic acid in partially purified preparation of cytosols. Cell lines such as hamster V79, BHK, rat hepatoma H4IIEC3G- or fibroblast 208F, which are sensitive to 1,6-dinitropyrene (1,6-DNP), possess high transferase activities ranging from 120-270 nmol/min x mg protein. In contrast, human lung cells NCI-H322, mouse and rat hepatoma cells BW1J and H5, respectively, which are resistant to 1,6-DNP contain no or low transferase activity of less than 15 nmol/min x mg. There was no apparent correlation between 1,6-DNP sensitivity and acetyltransferase levels in a few cell lines, e.g. rat hepatoma HTC, 2sFou and 5L, which express intermediate transferase activities ranging from 25-50 nmol/min x mg protein. The results suggest that acetylation is an essential step in activating 1,6-DNP to toxic products in mammalian cells. PMID- 2244343 TI - Cadmium-induced route-specific alterations in essential trace element homeostasis. AB - To determine if route-specific differences in essential trace element homeostasis occur after cadmium (Cd) exposure, selected metals (Zn, Fe, Ca, K, Cu, Mg, and Cd) were determined in testis, liver and lung after subcutaneous and intravenous Cd treatment. Cd by the subcutaneous route had the most pronounced effects on essential trace element homeostasis in the testes, increasing the concentration of Zn (51%), Fe (242%), Ca (95%), K (93%), and Cu (345%) in conjunction with a decrease of testicular Mg (46%), while few changes occurred with intravenous Cd. In the lung, modest changes of all elements except Ca and Cu were observed with Cd. However, alterations in Fe and Zn concentration were seen only in the liver. The present study suggests that levels of the essential metals in a particular tissue can be modified depending on the route of Cd administration. PMID- 2244344 TI - Trapping of short-lived electrophilic metabolites of pyrrolizidine alkaloids escaping from perfused rat liver. AB - It has been shown that a short-lived pyrrolic metabolite in fluid flowing out of isolated rat liver perfused with the pyrrolizidine alkaloid, monocrotaline, could be trapped by covalent reaction with a bed of immobilized thiol (thiol sepharose). Larger amounts of other pyrrolic metabolites, also in the fluid, were not trapped. This provided the first direct support for the widely held hypothesis that reactive pyrrolizidine alkaloid metabolites (dehydro-alkaloids) escape from the liver to damage the lungs of rats in vivo. The relatively smaller proportion of pyrrolic metabolite from retrorsine which could be trapped in this way was consistent with the known lack of pneumotoxicity of this alkaloid. The procedure described should be suitable for trapping other types of electrophilic metabolites. PMID- 2244345 TI - Turn it around: make the interview work for you. AB - 1. Because of the high costs involved in turnover and orientation, the interview process is an integral part of management. 2. Preparation is the most important part of any interview; dress appropriately, ask relevant questions, and know the job description and requirements. 3. Know your own philosophy and respond according to it, not what you perceive to be the "correct" response. PMID- 2244347 TI - Recovery centers: the wave of the future. PMID- 2244346 TI - When the patient dies: helping the family and staff to cope. AB - 1. Death of a family member or significant other is a traumatic experience for the survivors. Their psychological needs may be overlooked due to the discomfort of staff in dealing with matters related to death. 2. The nurse who has unresolved feelings concerning loss may lose control as well as lose professional effectiveness. 3. Failure by the nurse to recognize the dynamics of grief and attempts to prematurely end grieving can lead to serious consequences for survivors. Nurses who are aware of the needs of grieving persons can help to facilitate the process, cushion the trauma of loss, and set the basis for a healthy grieving process. PMID- 2244348 TI - AIDS focus. Surgical practice in hospitals: HIV and the surgical team. PMID- 2244349 TI - Tension reduction in the operating room. AB - Muscle relaxation, altering stressful thought patterns, verbalization to supportive team members, time management, and humor are all effective tension relievers. Whereas muscle relaxation, altering thought patterns, and time management may be effective individual techniques, verbalization and humor are techniques that involve others and maximize the use of support from others. However, in every situation, personality, culture, background, and levels of stress affect reactions to tension and color the reactions of others to strategies used to reduce tension. Thus, in all cases, the situation must be carefully assessed, and timing, discretion, and selectivity are of vital importance if the strategy is to be used effectively. In addition to the nurse's knowledge of tension reduction strategies that can be used in the operating room, optimal function can be promoted by a total lifestyle that attends to coping directly with tension. Adequate periods of planned relaxation and exercise, planned time off, proper nutrition, and diet must also be part of a holistic approach to help prevent and reduce disabling tension. PMID- 2244350 TI - Staff training avoids common problems. PMID- 2244351 TI - Nursing diagnosis into the 21st century: create the vision. PMID- 2244352 TI - Nursing our health-care system away from regulation. PMID- 2244354 TI - Veterinary Microbiology. Cumulative indexes. Volumes 1-25, 1976-1990. PMID- 2244353 TI - How to initially manage a pediatric trauma patient. AB - 1. Pediatric trauma care should be organized to assess the airway, breathing, circulation, disability/neurological status, and exposure of the child. 2. Because they have different body proportions, children may present with slightly different injuries than an adult. 3. Children react to trauma differently than adults. They may compensate for an extended period with tachypnea and tachycardia before cardiorespiratory failure occurs. PMID- 2244355 TI - [Vitamins and immunity. Biotin, pantothenic acid and riboflavin]. PMID- 2244356 TI - [Alcohol drinking, nutritional status and the incidence of ischemic heart disease according to the data of population studies]. AB - The method of dietetic interview was used in a strictly standardized epidemiological investigation of a random sample of males aged from 30 to 59 years (n-2537) in Kiev. A dependence has been revealed between the use of alcohol and disorders in the character of nutrition unfavourable in respect to coronary heart disease. A relationship has been established between the alcohol use and the incidence rate of such risk factors of coronary heart disease as hyperlipoproteinemia, excessive body mass, smoking, and the incidence of myocardial infarction. No relationship was recorded between alcohol kind and dose and the incidence of risk factors of coronary heart disease. PMID- 2244357 TI - [Caloric intake as an indicator of nutritional status of pregnant and nursing women]. PMID- 2244358 TI - [Development of vitamin D deficiency and immunologic disorders in children with glomerulonephritis]. AB - Biochemical symptoms of vitamin D deficiency and a sharp reduction in the number of T-lymphocytes in the peripheral blood were recorded in children suffering from glomerulonephritis. During the combined therapy using the compound "oksidevit " (1-hydroxyvitamin D3) the parameters characterizing D-vitamin providing became normal, and the number of T-lymphocytes in the peripheral blood was recovered. PMID- 2244359 TI - [Use of whey in the diet of children with chronic diseases of the biliary tract]. AB - The influence of whey on the function of the stomach, biliary system and pancreas was studied in 112 children with chronic cholecystocholangitis. It has been established that whey possesses a choleretic property and normalizes the exocrine function of the pancreas. Whey can be recommended as a therapeutic agent or an additive to products for diet therapy in the combined treatment of chronic diseases of the biliary system, especially, with concomitant affection of the stomach and pancreas. PMID- 2244360 TI - [Nutrition of children with hypotrophy in relation to hydrolysis and absorption of carbohydrates in the intestines]. AB - Characteristics of hydrolysis and absorption of mono-, di- and polysaccharides were studied in young children with hypotrophy of the alimentary and infectious genesis with the use of differentiated carbohydrate loadings. As a result of the study six variants of glycemic curves have been distinguished reflecting enteral assimilation of carbohydrates. They could be used for purposeful nutrition and correcting therapy of children with hypotrophy. PMID- 2244361 TI - [Revision of recommended amounts of main food products and energy requirements]. PMID- 2244362 TI - [Effect of sucrose on lipid metabolism in rats: confirmation of the disaccharide effect]. AB - Disaccharide effect of sucrose on lipid metabolism was confirmed in male Wistar rats (initial weight 119-127 g). The rats were given rations containing either sucrose (30% of total caloric++ value), or invert sugar, or starch only (control). The duration of the dietary period was 40 days. To study lipid metabolism the rats were injected i. p. with 1-14C-glucose and 3H-palmitic acid. 14C-radioactivity increased in the total lipid of serum and epididymal adipose tissue, in liver phospholipids and mostly in liver neutral lipids with the saccharose-supplemented diet but not with invert sugar-supplemented diet. In contrast, 3H-radioactivity in liver phospholipids decreased in rats that were given saccharose, no changes were recorded in the animals fed with invert sugar or starch. PMID- 2244363 TI - [Substantiation of the formula of human milk substitutes]. PMID- 2244364 TI - [Synergistic effect of antioxidants and phospholipids during oxidation of natural lipids]. AB - The effect of mixtures of phospholipids (PL) and natural antioxidants (AO)- tocopherol (TP), ubiquinone, ubichromenol, vitamin K, on the value of induction periods and on the rate of initiated oxidation of model substrates (++methyl oleate, mixtures of fatty acid methyl ethers, ethylbenzene) was studied at 60 degrees C. The possibility of synergism of different AO in the presence of PL has been established. It has been shown that the action of bioantioxidants in lipids may be increased 2.5-3.5 times. The dependences of TP and PL synergistic effect values on the concentration of the mixture components were studied. It has been shown that the synergistic++ effect grows proportionally to the amount of TP (in the interval studied up to 5 X 10(-3)M). At a constant concentration of TP the dependence of the value of induction periods increases linearly with the growth of PL concentration at the interval of 0.0-0.2%, and further it does not depend on the amount of PL. It has been shown that the synergism value does not depend on oxidation conditions and the nature of the oxidized substrate. PMID- 2244365 TI - [Medico-biological evaluation of sodium salt of nitrofurylacrylic acid as a food additive]. AB - Nitrofurylacrylic acid sodium salt is a substance of moderate toxicity. Its LD50 for male rats after oral administration comprises 1220 mg/kg, for female rats- 1400 mg/kg. The minimal toxic dose, in case of long-term administration comprises 14 mg/kg. At the level of doses from 0.04 to 4.0 mg/kg no mutagenic effect was detected. Oral and subcutaneous administration of minimal tolerance doses of the agent induced formation of malignant neoplasms developing, predominantly, from the epithelial tissue, with localization depending on the route of the agent administration. A conclusion has been made on impossibility of using this substance as a food additive. PMID- 2244366 TI - [Selenium levels in wheat flour from different regions of the USSR]. AB - Selenium content in the Soviet and imported wheat flour was studied in different regions of the USSR. Regions have been distinguished with high, medium and low level of selenium in wheat flour. PMID- 2244367 TI - [Effects of the species and quality characteristics on nitrate accumulation in vegetables grown in Pre-Urals]. PMID- 2244368 TI - [Effects of dietary cholesterol and plant oils on proteinase activity in the jejunal mucosa of rats]. PMID- 2244369 TI - [Effects of 3 types of modified fats on the weight of the body and separate organs and tissues of albino rats]. PMID- 2244370 TI - [The role of N.I. Lunin's dissertation in the history of discovery of vitamins]. PMID- 2244371 TI - Acoustic neuromas. PMID- 2244372 TI - Computed tomography and bronchoscopy in chest radiographically occult main-stem neoplasm diagnosis and Nd-YAG laser treatment in 8 patients. AB - We studied 8 adult patients with variable symptoms of cough, dyspnea, stridor, wheezing, or hemoptysis. Fiberoptic bronchoscopy in all showed complete or nearly complete endobronchial obstruction of a main-stem bronchus by neoplasm with a mean bronchial diameter of 1.9 mm +/- 1.6 mm (mean +/- standard deviation). In 4 patients, a lobar bronchus was also completely obstructed. No mass was visible on chest radiographs of any patient; however, computed tomography in each showed main-stem endobronchial obstruction, lobar obstruction (4 instances in 3 patients), and in 6 patients hypoperfusion of the involved lung. Computed tomographic scan showed additional abnormalities that were unsuspected on viewing chest radiographs or at bronchoscopy, including mediastinal adenopathy in 3 patients and an extraluminal tumor component in 4. After therapy with Nd-YAG laser, main-stem airway diameter increased to a mean of 9.6 mm +/- 1.0 mm (P less than .05) and pulmonary functions improved. Results suggest the complementary role of computed tomography and fiberoptic bronchoscopy in the detection and laser-treatment planning of chest radiographically occult severe neoplastic obstruction of the main-stem bronchus. PMID- 2244373 TI - Botulism among Alaska Natives. The role of changing food preparation and consumption practices. AB - Alaska Natives have one of the highest rates of food-borne botulism worldwide. All outbreaks have been associated with the consumption of native foods, but in recent years outbreaks have occurred in previously unaffected areas and have involved new food items. Five botulism outbreaks occurred between 1975 and 1985 in an area of southwestern Alaska without previous confirmed outbreaks and among one ethnic group, the Yupik Eskimo. Of the 5 outbreaks, 3 were associated with fermented beaver tail, a nontraditional native food recently introduced into the region. Preparation techniques vary widely within villages and among ethnic groups. Traditional fermentation techniques have changed over the past 50 years; current preparation methods used by some families and ethnic groups may be more favorable for Clostridium botulinum growth. Prevention efforts should be targeted at high-risk subgroups of Alaska Natives who appear to have modified traditional practices and increased their risk of food-borne botulism. PMID- 2244374 TI - HIV antibody seroprevalence among prisoners entering the California correctional system. AB - A cross-sectional blind study was conducted in the spring of 1988 to estimate the extent of human immunodeficiency virus (HIV) infection among inmates entering the California correctional system. Of the 6,834 inmates receiving entrance physical examinations during the study period, 6,179 (90.4%) had serum tested for the presence of HIV antibodies after routine blood work was completed and personal identifiers were removed. Seroprevalence was 2.5% (95% confidence interval, 2.1% to 3.0%) among the 5,372 men tested and 3.1% (95% confidence interval, 2.1% to 4.5%) among the 807 women tested. Seroprevalence was more than twice as high among men arrested in the San Francisco Bay Area as in those arrested elsewhere in the state. The regional differences in HIV seroprevalence observed among entering inmates mirror infection rates reported among intravenous drug users from the same regions. PMID- 2244375 TI - Immunizing California's children. Effects of current policies on immunization levels. AB - Data collected by the Immunization Unit of the California Department of Health Services from 1979 to 1987 were analyzed to determine the effects of changes in state policy on the immunization levels of children in California. By December 1986, 90% of all children entering kindergarten in California were adequately immunized, representing a 15% increase from 1979. Although California has shown substantial improvements, it still lags behind the national weighted average. Even with high levels of immunization at kindergarten entry, many toddlers of 7 months and 2 years old remain inadequately immunized. Children immunized solely in the private sector were more adequately immunized than those served by public health clinics; the public-private difference for infants aged 7 months was nearly twofold. PMID- 2244376 TI - Medical management of congestive heart failure. AB - The syndrome of congestive heart failure can result from a variety of cardiac disorders of which left ventricular dysfunction is the most common. The clinical presentation is determined by the interaction between cardiac dysfunction and a series of compensatory mechanisms that are activated throughout the body. Therapy for this disorder is best approached through an understanding of this complex relationship and an appreciation for the influence of preload, afterload, and contractility on cardiac performance. Recent important advances in therapy include the use of combined diuretic therapy, a better understanding of the value of the digitalis glycosides, and evidence that angiotensin-converting enzyme (ACE) inhibitors can relieve symptoms and prolong life. More intensive therapy earlier in the course of congestive heart failure appears to have some clinical benefit. The use of ACE inhibitors during this phase may delay progression of the underlying left ventricular dysfunction. Future therapy will be influenced by the results of ongoing trials that are testing both new agents and expanded indications for drugs that are currently available. PMID- 2244377 TI - Essential hypertension--where are we going? AB - This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. PMID- 2244378 TI - Human obesity. Exploding the myths. AB - This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Drs Paul G. Ramsey, Associate Professor of Medicine, and Philip J. Fialkow, Professor and Chair of the Department of Medicine. PMID- 2244380 TI - Coexistence of primary biliary cirrhosis and sarcoidosis. PMID- 2244379 TI - Is obesity due to a heritable difference in 'set point' for adiposity? PMID- 2244381 TI - Managing congestive heart failure medically--what have we learned? PMID- 2244382 TI - Consider the alternatives. PMID- 2244383 TI - Decriminalizing drug use. PMID- 2244384 TI - The 'aerospace syndrome'. PMID- 2244385 TI - Herpes zoster ophthalmicus--the changing epidemiology and its implications for treatment. PMID- 2244386 TI - Radon in California homes. PMID- 2244387 TI - [Carbamazepine in the treatment of psychiatric diseases: effects and side effects]. AB - The use of carbamazepine in psychiatry has widened its scope in the last years. Its efficacy is proven best in manic syndromes, in the prophylaxis of manic depressive illness and in the treatment of alcohol withdrawal symptoms. Beyond this, carbamazepine has been used successfully in depression, schizophrenia, organic psychoses and intermittent explosive disorder. The manifold therapeutic possibilities should not make forget the side effects. The most severe effects to be expected are impairment of the hematopoietic system and skin reactions. Vegetative and neurotoxic effects most commonly occur in the beginning of therapy, after increasing the dosage and in case of intoxication. Further possible side effects are disturbances of hepatic, thyroid, renal and cardiac function, of immune response, water balance and calcium metabolism. Monitoring of these parameters during therapy with carbamazepine is necessary. PMID- 2244388 TI - [Epidemiology of attempted suicide and overdose in drug dependent patients]. AB - 48 fatalities (11 female, 37 male) among drug addicts are registered in Vienna in 1988. 96 committed suicides and 401 suicide attempts are reported among young Viennese in 1987. In order to examine the connection between suicide, parasuicide and drug addiction at the drug out patient clinic of the Psychiatric University Hospital of Vienna, 223 patients were investigated in February 1989. PMID- 2244389 TI - [Predictors of multiple sclerosis development trends with special reference to "questionable initial manifestations"]. AB - Within 10 years we have had evidence in our department of 173 cases of proven multiple sclerosis (MS) and 63 cases which primarily were called by us: "bland entzundliches Geschehen" (BEG) instead of "possible first onset of multiple sclerosis". 44% of these cases remained as a singular manifestation, whereas 56% developed to established MS. This underlines our proposition of a new classification which does not call such questionable first symptoms as "possible first onset of MS" but as "bland entzundliches Geschehen". This is much less severe and prejudicatory for the bearers of such symptoms. Furthermore we could demonstrate clear correlations between clinical and laboratory findings and the probability of development of MS and the improbability of such a development, respectively. We could not find such predictors up till now in the literature. The several laboratory parameters, relevant for MS (not only with regard to BEG, but also to the whole population which clinically proven MS) could be tested regarding their sensitivity. As a remarkable result, to our knowledge not mentioned so far in the literature, we could demonstrate the flicker-fusion analysis to be the leading laboratory test. In addition it is a very simple laboratory method, as far as time and money are concerned. It is at least as valid as visual evoked potentials which in the literature are considered to be the most sensible test. Taking into account the few cases examined with the magnet resonance tomography until today, this method, seems to be less sensitive than flicker-fusion-analysis. We do not have a 100% laboratory method at our disposal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244390 TI - [Current overview of diagnostic possibilities of complement analysis]. AB - The complement system is composed of at least 21 serum proteins and 8 cell surface receptors sensitive to complement components or their fragments. Qualitative and quantitative analysis of complement components in clinical samples has become standard procedure in many laboratories thanks to the availability of easy-to-perform test kits. However, interpretation of results is still a task that requires great skill and the situation are rare, in which analysis of the complement system goes beyond diagnosis into therapeutic consequences. The present paper is an update of previous similar reviews now available in the international literature; in addition, the author attempts at bringing the often complicated world of complement and clinical practice together and thus contributes to answering the question: what should the clinician know about complement? PMID- 2244391 TI - Advances in diagnosis and treatment in clinical immunology. PMID- 2244392 TI - Amiodarone: a postmarketing evaluation of monitoring for drug-induced toxicity. AB - Amiodarone, an antiarrhythmic drug with predominantly class III effects, has demonstrated serious adverse drug reactions and interactions. The Departments of Pharmacy and Cardiology retrospectively evaluated the monitoring parameters at this institution. Criteria based on current literature were developed. Twenty-six patients were administered amiodarone, qualifying for entry into the audit. Of these patients, seven were excluded because their medical records were unavailable or incomplete. The 19 eligible patients were hospitalized during initiation of therapy and followed in the Outpatient Cardiology Clinic. The collected data extracted from the medical charts were compared with the following elements of the criteria selected: baseline evaluation prior to the start of therapy; monitoring for signs of pulmonary, hepatic, thyroid, cardiac, ophthalmologic, neurologic, and dermatologic toxicity; and evaluation of potential drug interactions with digoxin and warfarin-type anticoagulants. The percentage of criteria elements appropriately monitored on each patient ranged from 82 to 100 percent, with an average of 91 percent. The most frequently overlooked parameters were warning the patient of a possible photosensitivity reaction, decreasing the digoxin dose if the patient was concurrently taking amiodarone, and performing a slit-lamp examination every six months. Frequent examination of the patient's total organ system and laboratory tests, in addition to patient education, are essential to safe monitoring of amiodarone therapy. PMID- 2244393 TI - Ectropion: an adverse effect of etretinate therapy for psoriasis. PMID- 2244394 TI - Possible cyclosporine-associated thrombocytopenia. PMID- 2244395 TI - Precaution with titrating nortriptyline after the use of fluoxetine. PMID- 2244396 TI - Clindamycin stability. PMID- 2244397 TI - Tryptophan and eosinophilia myalgia syndrome. PMID- 2244398 TI - Equipotent dosing of estrogens? PMID- 2244399 TI - Comment: Famotidine stability. PMID- 2244400 TI - Comment: Dexamethasone binding. PMID- 2244401 TI - Comment: Pharmacy specialization. PMID- 2244402 TI - Correction: Seizure activity associated with antipsychotic therapy. PMID- 2244403 TI - Flurbiprofen versus diclofenac for the treatment of osteoarthritis of the knee. AB - Seventy-four patients were enrolled in this double-blind, randomized single center study to evaluate the therapeutic effectiveness of 50 mg tid regimens of flurbiprofen or diclofenac sodium in patients with osteoarthritis of the knee. By chance, the flurbiprofen patients had a significantly more advanced disease status at baseline than their diclofenac-treated counterparts. However, at subsequent follow-up evaluations, both treatment groups experienced a significant reduction in disease severity regardless of the baseline differences. No serious safety problems were associated with either investigational therapy. The frequency of reported medical events were distributed equally between the flurbiprofen and diclofenac groups. Although the imbalance in disease severity between treatment groups made a rigorous statistical interpretation of the results very difficult, the data from this clinical trial tend to support the equiefficacy of 50 mg tid regimens of flurbiprofen versus diclofenac for treating osteoarthritis of the knee. PMID- 2244404 TI - Correlation of free phenytoin to serum albumin in cancer patients. AB - The objectives of this study were to compare the total and free phenytoin serum concentrations of cancer patients with hypoalbuminemia with those of cancer patients with normal serum albumin and to correlate the percentage of free phenytoin with the albumin concentration. A total of 22 patients were studied, 13 with normal albumin concentration and 9 with low albumin. The mean free phenytoin in the normal albumin group was 9.9 (+/- 1.3) percent and 17.6 (+/- 4.6) percent in the low albumin group. With the groups combined, the mean free phenytoin was 13.1 percent (range 8.3-22.2) with the albumin range of 20-45 g/L. There was a significant negative correlation (r = -0.9, p less than 0.001) between the percentage of free phenytoin and the measured serum albumin. In cancer patients, the serum albumin concentration appears to be the key factor that determines the percentage of free phenytoin. In cancer patients with low serum albumin concentration, the total and free phenytoin concentration should be measured for adequate assessment of phenytoin therapy. PMID- 2244406 TI - Assessment of the Florida Pharmacist Self-Care Consultant Law using patient profile and prescription audit methods. AB - This article examines pharmacist nd physician prescribing patterns during the first two years of the Florida Pharmacist Self-Care Consultant Law. Nineteen pharmacies were audited. The mandatory patient profiles were audited for a two year period, and the prescription files were audited for a five-year period. For the nine pharmacies maintaining patient profiles, the prescribing activities of the pharmacists almost double from the first year to the second year. However, these prescriptions made up a very small portion of the total. Pharmacist prescribing appeared to be limited to three primary drug categories: topical pediculicides (lindane shampoo), oral analgesics, and otic analgesics; these comprised 82 percent of all pharmacist-generated prescriptions. PMID- 2244405 TI - Evaluation of pharmacists' practice in patient education when dispensing a metered-dose inhaler. AB - Improper inhalation technique with beta-agonist metered-dose inhalers (MDIs) decreases efficacy of the bronchodilator. The success of demonstrating the correct technique and the pharmacist's role in patient education has been reported. To obtain information regarding the routine patient education practice of pharmacists when dispensing a beta-agonist MDI (albuterol), the following study was performed. Fifty-two prescriptions for an albuterol MDI were presented to 52 randomly chosen community pharmacists in three Tennessee cities. Twenty-six independent and 26 chain pharmacies wer evaluated. Pharmacists' practice with regard to patient education, instruction, and demonstration of the correct usage of the MDI was observed and recorded. Overall, 13 percent of the pharmacists initially offered to educate the patient-investigator (PI) regarding the correct usage of the MDI without being asked for information. Fifty-three percent of pharmacists offered information only upon being asked specifically how to use the MDI. Of the pharmacists who offered to educate the PI, 71 percent discussed less than half of the eight steps correctly. Only 1 of the 52 pharmacists actually demonstrated MDI inhalation technique, and this in response to a request. No pharmacist asked the PI to perform the technique while he/she observed. No pharmacist offered information on delivery enhancement devices. Our results demonstrate that few pharmacists educate patients on the correct usage of an MDI, and that many pharmacists are not aware of the correct technique. PMID- 2244408 TI - Sodium loading treatment for amphotericin B-induced nephrotoxicity. AB - The increased frequency and duration of antifungal treatment with amphotericin B in immunocompromised patients has stimulated a great deal of research into the mechanisms of its nephrotoxic effects and treatment modalities designed to attenuate these effects. A review of amphotericin B-induced nephrotoxicity, the underlying pathophysiologic mechanisms, and the role of salt loading as a means of minimizing renal impairment are described. Both animal and human studies regarding the efficacy of sodium loading are presented as well as a case report describing the use of salt supplementation over a prolonged course of therapy. PMID- 2244407 TI - High-dose phenylephrine infusion in the hemodynamic support of septic shock. AB - A 75-year-old man with hyperdynamic septic shock and vasodilation was successfully supported hemodynamically for 88.5 hours through the use of a continuous infusion of phenylephrine at dosages up to 360 micrograms/min. The only other vasoactive compound administered was dopamine at a dosage of 3.4 micrograms/kg/min. Hemodynamic evaluation indicated improvements in mean arterial pressure, cardiac output, and oxygen transport parameters during the period of hemodynamic support, which did not indicate a detrimental effect on perfusion of vital organs and tissues despite the use of this vasoconstrictor. Phenylephrine's pharmacologic properties may represent an advantage for its use as a vasoconstrictor over catecholamines such as norepinephrine and dopamine, particularly in patients who develop tachyarrhythmias with these agents. The pharmacology, dosage, and appropriate monitoring of therapy with phenylephrine in patients with septic shock are discussed. PMID- 2244409 TI - Octreotide use in AIDS. PMID- 2244410 TI - Mechanical ventilation. AB - Among the many advances made in intensive care therapeutics in recent years, few have rivaled the impact of mechanical ventilators. Their expanded use affects all who practice in the critical care setting. This article reviews the physiologic basis for mechanical ventilation, how ventilators are classified, the various modes, and specific indications. A basic introduction is made into ventilator set up, weaning techniques, adjunctive drug therapy, and complications. The pharmacotherapy specialist who understands interactions between patients and ventilators, and the effects of mechanical ventilation on cardiopulmonary function will be best equipped to individualize drug therapy. PMID- 2244411 TI - A profile of alcohol and prescription drug abuse in a high-risk community-based elderly population. AB - Substance abuse among the elderly is relatively common but often remains undetected or ignored by health and social workers. Psychosocial and health factors related to the aging process are the major contributors to alcoholism and other drug abuse. It is estimated that between two and ten percent of individuals over the age of 60 suffer from alcoholism. This article profiles alcohol and prescription drug abuse among the geriatric clientele of Elderly Services of Spokane (ESS), a division of the Spokane (Washington) Community Mental Health Center. In addition to traditional channels, ESS uses a unique gatekeeper network to identify high-risk, community-based elderly. Elderly persons referred by gatekeepers are regarded as "hidden" elderly and at highest risk; notably, 37 percent of ESS clients are referred via this mechanism. Case management records of 1668 ESS clients were reviewed for a history of alcoholism, and a total of 161 persons (9.6 percent) were diagnosed with either primary or secondary alcohol abuse. Fifty subjects (about five percent of the average active ESS caseload) were referred for prescription drug abuse. Misused prescription drug classes were sedative-hypnotics, antianxiety agents, and analgesics. Diazepam, codeine, meprobamate, and flurazepam were the top four agents, and 92 percent of the subjects were found to have a duration of prescription drug abuse in excess of five years. A 60 percent correlation between prescription drug abuse and previous or active alcoholism was found. Additional characteristics of the geriatric study population are discussed in detail, including specific psychosocial factors, source of referral, age, gender, living situation, marital status, psychiatric history, and presence of polypharmacy. PMID- 2244412 TI - Flumazenil: a benzodiazepine antagonist. AB - Although benzodiazepines have been proven safe and effective for the induction and maintenance of sedation, some instances require the reversal of these events prior to the natural process of metabolism and elimination. Flumazenil, a 1,4 imidazobenzodiazepine, is an antagonist that can reduce or terminate benzodiazepine effects in a dose-dependent manner. The antagonist acts by the competitive inhibition of benzodiazepines at their central nervous system receptor sites. When administered intravenously in incremental doses, flumazenil allows for optimal patient response on an individual basis. Despite its short elimination half-life, small doses of flumazenil are usually effective in producing benzodiazepine reversal. Flumazenil's short duration of activity is due to its rapid hepatic metabolism and elimination. Intravenous antagonist doses of 0.2 mg followed by 0.1 mg/min to a total dose of 1 mg have produced significant results in reversing benzodiazepine sedation. As much as 5 mg of flumazenil have been necessary when treating benzodiazepine or mixed-agent intoxications. In such situations, response rarely exceeds a duration of one hour. If resedation occurs, additional doses or an infusion of the antagonist may provide the desired response. Flumazenil is well tolerated locally as well as systemically. Nausea and vomiting occurring after anesthesia is the most documented adverse effect in both placebo and treatment populations. However, there has been no significant difference in the occurrence of vomiting in placebo compared with flumazenil treated subjects. Careful observation and slow reversal of central nervous system depression is crucial in the avoidance of benzodiazepine withdrawal in those patients dependent upon these agents. Flumazenil appears to provide a mechanism for the safe and effective reversal of benzodiazepine-induced sedation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244413 TI - Detecting drug interactions: a review of the literature. AB - This article provides a historic overview of drug interaction screening and reviews 19 studies that have sought to measure the frequency of drug interactions. Differences in study designs, methodologies, and definitions contribute to considerable variation in the reported incidence rates, which ranged from 2.2 to 70.3 percent for all potential drug interactions. The percentage of patients actually experiencing symptoms that could be attributed to a drug interaction, however, ranged from 0 to 11.1 percent. The relative importance of drug interactions as a clinical problem remains unclear. Screening programs that do more than simply identify large numbers of patients who receive potentially interacting drug combinations without indicating which subpopulations of these individuals are likely to be harmed by the drugs have not yet been developed. PMID- 2244414 TI - Treatment of digitalis intoxication with emphasis on the clinical use of digoxin immune Fab. AB - Many studies and cases of digitalis intoxication have been reported since the time of William Withering's first publication in 1785. Recognition and management of digitalis toxicity is challenging. Before digoxin immune Fab was commercially available, treatment consisted of managing the signs and symptoms of toxicity until the digitalis was eliminated. Digoxin immune Fab offers a safe, effective, and specific method of quickly reversing digitalis toxicity. Factors that must be considered with the clinical use of this agent include the dosage calculation, administration technique, postdose monitoring, pharmacokinetics, mechanism of action, interference with commercially available digoxin assays, partial neutralizing dosing, rebound of free digoxin, and indications for use. For severe, life-threatening toxicity, digoxin immune Fab is the treatment of choice. PMID- 2244415 TI - [Scoring systems for severe intra-abdominal infections]. AB - In the following paper a review is given on the development of scoring-systems of severe intraabdominal infections till now. After a critical reflection on various systems a heuristic assessment is shown in the summing-up about their possible utility in the future. At present the APACHE II index, the sepsis score by Elebute and Stoner and the Mannheim peritonitis index meet practically requirements for good scores by different revising questions. PMID- 2244416 TI - [The application of scoring systems for surgical intensive care patients]. AB - In a prospective study above five months 8 classification-systems were examined to allow a grading of the severity of diseases in surgically intensive patients (n = 44). The aim was to check their practicability in clinical handling and their application as a parameter of course of critical ill patients. In spite of the relative small number of patients, in the result came the strong and weak points of scoring-systems for expression. For surgically intensive patients are recommended the APACHE-II index and the sepsis-score by Elebute and Stoner for cases with severe infections. PMID- 2244417 TI - [Results of sonographically-guided percutaneous procedures as therapy of liquid filled space-occupying lesions in acute abdomen]. AB - In the period from 1985 emergency sonographic study has been performed in 56 patients. In 44 cases we found intraabdominal abscesses, in 5 liver cysts with internal bleeding, in 5 postoperative lymphatic cysts, and in 2 cases loculated pleural empyemas. In 35 patients ultrasound guided therapeutic procedures were performed; there were 13 punctures (some repeated) and 22 drainages. In 29 patients no further surgical treatment was necessary. The over all success rate was 82.9%. One patient developed bacteremia after percutaneous drainage and an other developed subcutaneous abscess (complication rate: 5.7%). When abscesses are sufficiently drained no antibiotic therapy is needed. PMID- 2244418 TI - [Acute phlegmonous gastritis]. PMID- 2244419 TI - [Impaired granulocyte function in infected peritoneal exudate]. PMID- 2244420 TI - [Development and critical evaluation of pancreatic duct occlusion]. AB - The three original aims of pancreatic duct occlusion (PDO) were first the reduction of early complications after Whipple's operation in chronic pancreatitis and carcinoma as well as segmental pancreas transplantation, second to finish the inflammation in cases of chronic pancreatitis and third to protect the B-cell function in remained or transplanted pancreas. We have compared PDO by Tissucol and Ethibloc with non-occluded pancreases up to 3 years after Whipple's operation in patients with chronic pancreatitis and carcinoma and in patients with autologous segmental pancreas transplantation. In concluding the results one can say that PDO is of high value with regard to early complications in patients with pancreas carcinoma. In these patients and in autologous pancreas transplantation the PDO by Tissucol seems to have more protective effect on B cell function than the other approaches. In patients with chronic pancreatitis and Whipple's operation the PDO was without value neither for early complications, these are very low anyhow, nor B-cell function. PMID- 2244422 TI - [Progressive pneumoperitoneum. For preoperative preparation in giant abdominal soft tissue hernias]. AB - Without special preoperative preparation giant hernias of the abdominal wall which have "forfeited their right of domicile" can only be repaired under great difficulties and with substantial risk of the patient. A method of preliminary enlargement of the peritoneal cavity is described - the progressive pneumoperitoneum - which minimises the technical difficulties and the patient's risk. The "right of domicile" is regained. Two case reports illustrating the procedure are given. PMID- 2244421 TI - [A new method for pseudocysto-duodenostomy as therapy in pancreatic pseudocyst in chronic pancreatitis]. AB - Reference in the surgical literature to the use of pseudocysto-duodenostomy whether laterolateral by Ombredanne [6] or transduodenal by Kerschner [4], is uncommon. The author with the aid of specially designed three-jaw prong, now, prefer to use pseudocysto-duodenostomy. From 1970, 411 patients underwent surgery for complicated chronic pancreatitis. 67 of the 93 patients requiring an internal cysto-intestinal procedure were treated by pseudocysto-duodenostomy; 11 additional patients were treated by derivation in the first retroperitoneal transposed jejunal loop. Postoperative mortality for the first month was 0%. The actuarial survival rate at 5 years was 86.9%. These satisfactory results have encouraged us to compare this new operative method with cystojejunostomy. It allows pancreatic secretions to drain into their natural anatomical site. Compared with external drainage it avoids the often prolonged and costly complications. PMID- 2244423 TI - [Experiences with fibrin glue-coated collagen fleece]. AB - Fibrin-adhesive coated collagen fleece (Tachocomb) was used for haemostasis on 57 patients on whom different types of operations had been performed. These had been partial hepatectomies (21 cases), liver transplantations (six), and partial pancreatectomies (nine). Haemostatic effect on diffuse oozing haemorrhage was satisfactory. However, collagen fleece patches were only 8 cm X 4 cm in size and should be available in larger dimensions, particularly when it comes to larger sealing areas. PMID- 2244424 TI - Complete extraperitoneal cecostomy. An ileo-colic diversion procedure after colonic operations. AB - A new external diversion technique of ileo-colonic content through an extraperitoneal cecostomy is presented. This technique avoids the draw back of the classical cecostomy: intraperitoneal leakage intestinal content, reoperation for closure the stoma. The procedure is simple, easily performed and efficient in protecting the colonic anastomosis, and diverting the ileo-colonic content. PMID- 2244426 TI - The environment is a health care issue. PMID- 2244425 TI - Postprandial gallbladder emptying in patients after pancreatoduodenectomy. A preliminary report. AB - The study was undertaken to establish the pattern of gallbladder emptying in patients after pancreato-duodenectomy with the gallbladder preserved. 14 patients were examined. The preliminary examination revealed pathologic changes of the gallbladder in 5 patients, they were excluded from further investigations. The mean initial gallbladder volume, and the mean gallbladder maximum ejection fraction in patients after pancreatoduodenectomy were significantly lower as compared with controls. The pattern of gallbladder emptying was markedly flattened in the majority of patients, accompanied by alternate emptying and refilling of the gallbladder. On the basis of the above-mentioned observations we confirm the necessity to remove the gallbladder during pancreatoduodenectomy. PMID- 2244427 TI - Law and the abused woman. Part three. What if your spouse threatens or hurts you? PMID- 2244428 TI - Insubordination and incompetence--a nurse's dilemma. PMID- 2244429 TI - 1991 75th anniversary AARN. Our history--a proud heritage: the war years and beyond--1940-49. PMID- 2244430 TI - Identification of the need for nursing education. PMID- 2244431 TI - From where I sit. PMID- 2244432 TI - Transplantation update. PMID- 2244433 TI - Islet cell transplantation in patients with diabetic nephropathy. PMID- 2244434 TI - An ethnography of the spinal cord injury unit. Part two. PMID- 2244435 TI - Developing a research team: involving staff nurses and students. PMID- 2244436 TI - Non-invasive blood pressure monitoring during head-up tilt using the Penaz principle. AB - Continuous blood pressure measurement by a non-invasive means is of clinical utility in many situations where changes in cardiovascular hemodynamics and blood volume distribution are likely to occur. We have compared blood pressure measurements using the Penaz principle (Finapres, Ohmeda) to an intra-arterial catheter system during head-up tilt (reverse Trendelenburg's position) which models central hypovolemia. Twelve healthy volunteers were raised to a 60 degree head-up tilt position for 60 min or until presyncope occurred. Seven subjects developed presyncopal symptoms at a mean time of 38 +/- 6 min with blood pressure measured by the Penaz principle falling from 140 +/- 8/72 +/- 4 to 82 +/- 10/54 +/- 6 mmHg (18.7 +/- 1.1/9.6 +/- 0.5 to 10.9 +/- 1.3/7.2 +/- 0.8 kPa) (P less than 0.01), at which point they were returned to a horizontal position with an immediate rise in blood pressure. During the maximal drop in blood pressure, heart rate decreased from 82 +/- 7 to 45 +/- 5 (P less than 0.01). Overall, the non-invasive system had a correlation coefficient of 0.98 as compared to the intra-arterial method and ECG for blood pressure and heart rate in all 12 subjects during rest, tilt, and recovery. We conclude that the Penaz principle apparatus is a useful monitor of symptomatic hypotension during central hypovolemia. PMID- 2244437 TI - Responses to barbiturates of isolated dog cerebral and mesenteric arteries contracted with KCl and prostaglandin F2 alpha. AB - In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2 alpha (PGF2 alpha), the addition of pentobarbital (10(-5) to 10(-3) mol.l-1) caused dose-related relaxation, whereas thiamylal and thiopental in a low concentration (10(-5) to 10(-4) mol.l-1) caused further contraction and in a high concentration (10(-3) mol.l-1) profound relaxation. Thiobarbiturate-induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2 alpha. In cerebral and mesenteric arteries exposed to Ca(++)-free media for 60 min and treated with KCl or PGF2 alpha, reintroduction of Ca++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca(++)-induced persistent contraction was attenuated by pretreatment with pentobarbital (10(-4) to 10(-3) mol.l-1) and thiamylal (10(-3) mol.l-1); the attenuation was greater in arteries treated with KCl than with PGF2 alpha. The Ca(++)-induced contractions of mesenteric artery treated with PGF2 alpha were potentiated by 10(-4) mol.l-1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl-induced depolarization than by a stimulation of PGF2 alpha receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor-operated Ca++ channel for PGF2 alpha. PMID- 2244438 TI - The pericardium exerts constraint on the right ventricle during cardiac surgery. AB - The right ventricle may be particularly susceptible to the effects of pericardial constraint. This study examined the effects of pericardiotomy on right ventricular function. Twenty-four anesthetized patients with coronary artery disease, but without evidence of pericardial pathology, were studied. Anesthesia consisted of fentanyl (100 micrograms.kg-1), diazepam, pancuronium, and 100% oxygen. The American Edwards REF-1 Cardiac Output Computer, rapid-response thermistor pulmonary arterial catheter, and a radial arterial catheter were used to measure hemodynamic variables. Baseline measurements were obtained with the sternum fully retracted. The measurements were then repeated following pericardiotomy by a midline incision. There were significant (P less than 0.05) changes in systolic arterial pressure (+4.5%), mean arterial pressure (+3.7%), systolic pulmonary arterial pressure (+11.8%), cardiac output (+9.1%), stroke volume (+6.9%), right ventricular end-diastolic volume (+7.6%), and right atrial pressure (-8.6%). In the current study, pericardiotomy augmented right ventricular diastolic filling and stroke volume, while the right atrial pressure decreased. These results support the concept of pericardial constraint. PMID- 2244439 TI - Anaesthesia in malignant hyperthermia-susceptible patients without dantrolene prophylaxis: a report of 30 cases. AB - The intra- and postoperative course of 30 anaesthetics in 24 MH-carriers verified by in vitro contracture tests is reported. None of the patients received dantrolene prophylactically and only agents known to be nontriggers were used for anaesthesia. Neither MH-related changes in perioperative heart rates, body temperatures, and CK levels nor any other symptoms of MH were observed. We conclude that the prophylactic use of dantrolene is not necessary in patients suspected to be prone to MH if triggering agents are avoided and the patients are closely monitored. PMID- 2244440 TI - Heat and moisture exchangers and the body temperature: a peroperative study. AB - The importance of conditioning the inhaled gas for maintaining the body temperature during artificial respiration was investigated. The mean body temperature (MBT) was deduced from readings from five measuring sites, four of which were situated at the skin and the fifth in the rectum. Temperature recordings were made every 15th min. Twenty patients were admitted to the study. In 10 patients a heat and moisture exchanger was used (the HME group), and the other 10 were ventilated without an HME (the control group). The patients were normoventilated, and a non-rebreathing system was used. All operations were made in the ENT-region of the body. Great care was taken to avoid variation of external factors that may affect the MBT. We found that the MBT decreased 0.2 degrees C/h less in the HME group than in the control group. If corrections were made for differences in amounts of fluids given and age factors, a difference in heat loss of 41.6 kJ/h between the two groups could be derived from this figure. This difference was statistically significant. Our finding correlated fairly well with a predicted reduction of heat loss of 26.0 kJ/h for the type of HME used. A certain margin of error seemed to be inevitable in measuring body temperatures, and the reason for this is discussed. Our results support the fact that the investigation is adequately designed, and that the heat conserved with an HME is rather low. PMID- 2244441 TI - The maternal hemodynamic effects of bupivacaine-epinephrine mixture used for obstetrical anesthesia. AB - The maternal hemodynamic effects of bupivacaine (0.5%)-epinephrine (5 micrograms/ml) mixture used for lumbar epidural anesthesia were studied with an impedance cardiograph and an automated blood pressure device in term gravidas undergoing elective cesarean section. Following i.v. hydration with 2000 ml Ringer's lactate solution, 16 patients received bupivacaine-epinephrine mixture and 16 patients plain bupivacaine in 5-ml increments to a T4 level. Measurements were made before anesthesia, at T10 and at T4 sensory levels. Results were analyzed using analysis of variance (ANOVA) and the least significant difference method at P less than 0.05. In the epinephrine group, at T10 level, the diastolic (D) and mean (M) pressures decreased significantly 11 +/- 3, and 10 +/- 1% (mean +/- s.e. mean) respectively with no significant change in the S pressure. No significant changes were seen in the plain group. At T4, the S, D and M pressures decreased significantly 8 +/- 2, 18 +/- 4 and 16 +/- 2% in the epinephrine group. In the plain group the decrease in each one of these pressures was less than 5% and was not significant. In the epinephrine group, S, D and M pressures decreased significantly more than they did in the plain group at T10 and T4. Systemic vascular resistance decreased significantly from control values by 19 +/- 6% at T4 in the epinephrine group with no significant changes in the plain group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244442 TI - Partial reversal of the cerebral effects of isoflurane in the dog by theophylline. AB - The cerebral effects of adding theophylline to 1.4% isoflurane anaesthesia were studied in five dogs by a sagittal sinus outflow technique with direct measurement of the cerebral blood flow (CBF) and calculation of the cerebral metabolic rate for oxygen (CMRo2). Three 3 mg.kg-1 doses of theophylline were given with intervals of 10 min. Five min after the second and third dose, when the mean theophylline plasma concentration was 41 and 65 mumols.1(-1), respectively, CMRo2 had increased significantly with a mean value varying between 15% and 13%, and the EEG had changed from a sleep pattern to a more awake pattern in the four dogs with evaluable recordings. There were no significant changes in CBF or mean arterial blood pressure (MABP). It is concluded that the adenosine receptor antagonist theophylline in this study partially reversed the cerebral effects of isoflurane. PMID- 2244443 TI - Forty-six "first anaesthetics" in the world. AB - Data about forty-six "first anaesthetics" have been collected from the literature. This makes it possible to get an impression of how fast the news of either anaesthesia spread to Europe and other parts of the world. Most European countries had the news within 4 months and other parts of the world within 9 months. The use of ether seems not to have spread faster in the US than in Europe. PMID- 2244444 TI - Patients' experiences of postoperative respirator treatment--influence of anaesthetic and pain treatment regimens. AB - The influences of premedication, anaesthetic agents, and postoperative sedation and pain treatment regimens on the experiences of postoperative respirator treatment of surgical patients (n = 107) have been assessed. Of the patients, 55% recalled the respirator treatment. Administration of anticholinergic drugs and halogenated anaesthetic agents was found to impair the memory process and reduce the number of recallers, and sedation in the ICU with benzodiazepines was found to decrease the number of discomforts experienced by the recalling patients. Most of the patients who received treatment postoperatively for pain, mainly by epidural administration of local anaesthetic agents and/or morphine, recalled the respirator treatment period (85%), as compared to only 50% of the patients receiving intravenous opioids. The number and type of complaints experienced by patients receiving epidural pain treatment did not, however, differ from those reported by intravenously treated patients, and no significant adverse psychological reactions seemed to occur. It is concluded that the use of mainly regional techniques, when appropriate, for pain treatment of surgical patients needing postoperative ventilatory support seems advantageous. The primary aim of relieving pain from the wound area is achieved, allowing such light intravenous sedation and pain treatment that the possibility of communication and giving comforting reassurance is maintained. Such nursing care may be more efficient in helping the patient to cope with the stressful respirator treatment situation then heavy intravenous sedation and pain treatment regimens. PMID- 2244445 TI - Pulmonary clearance of 99mTc-DTPA during halothane anaesthesia. AB - We studied the integrity of the alveolo-capillary barrier during different forms of anaesthesia by measuring the pulmonary clearance of inhaled 99mTc-DTPA. We studied four groups of rabbits. Groups I and II were anaesthetized with nembuthal only and the fractional concentration of inspired oxygen (F1O2) was 0.30 and 1.00, respectively. Groups III and IV were anaesthetized with 1% halothane and F1O2 was 0.30 and 0.99, respectively. 99mTc-DTPA was administered as a fine aerosol and the clearance of the tracer from the lungs was subsequently measured with a gamma camera. The mean half-life of the tracer in the lungs in Groups I-IV was 60, 58, 59 and 26 min, respectively. The rapid pulmonary clearance of 99mTc DTPA in Group IV indicates that halothane in combination with high oxygen concentration increases the permeability of the alveolo-capillary barrier. This may be due to effects on the pulmonary surfactant system and/or the alveolar epithelium. PMID- 2244446 TI - Haemodynamic effects of famotidine and cimetidine in critically ill patients. AB - To compare the cardiovascular effects of the histamine H2 receptor antagonists, famotidine and cimetidine, in critically ill patients, seven ICU patients were given 20 mg of famotidine or 200 mg of cimetidine intravenously in a randomized fashion. Each patient was studied on 2 separate days. In a random fashion, they received famotidine on one of the days and cimetidine on the other. Mean systemic arterial pressure (MAP) was maximally decreased 2 min after intravenous cimetidine from 103 +/- 10 (13.7 +/- 1.3 kPa) (mean +/- s.d.) to 83 +/- 15 mmHg (11.1 +/- 2.0 kPa) (P less than 0.05). MAP returned to control values 8 min after administration of the drug. Systemic vascular resistance (SVR) was significantly decreased during the 8-min observation period (P less than 0.01). In contrast, famotidine produced little haemodynamic effect over the 8-min period. Therefore, we suggest that famotidine may be a better H2 antagonist than cimetidine in critically ill patients requiring vasoconstrictor drug support, since it avoids the significant decrease in systemic blood pressure and peripheral vasodilation seen after cimetidine. PMID- 2244447 TI - The effect of nitrous oxide on EEG spectral power during halothane and isoflurane anaesthesia. AB - The effect of N2O on EEG during halothane and isoflurane anaesthesia was studied in 24 elective-surgery patients. The total EEG power and various power bands were analysed with fast Fourier transform power spectra. Anaesthesia was induced by mask. EEG analysis was performed from the data collected before induction and during steady-state halothane and isoflurane anaesthesia with and without N2O. In both halothane and isoflurane anaesthesia, N2O had a significant effect on EEG. Alpha- and beta-range EEG power and total power decreased during N2O in both groups. Delta- and theta-range power increased during N2O in the halothane group. The study shows that the effect of nitrous oxide should be taken into consideration when EEG is being studied or monitored during anaesthesia. PMID- 2244448 TI - Hemodynamic effects in dogs of nitrous oxide-meperidine and meperidine, respectively, in comparison with nitrous oxide. AB - The aim of this investigation on dogs, was to examine the hemodynamic effects of nitrous oxide (N2O) plus meperidine and of meperidine with room air ventilation, respectively, compared with those of N2O on its own. When meperidine (bolus dose 3 mg.kg-1 and continued infusion 4 mg.kg-1.h-1) was added to 80% N2O, mean arterial blood pressure fell from about 20 to 10 kPa (150 to 75 mmHg), as a result of a decrease in peripheral vascular resistance, but no compensatory changes in cardiac output were seen. When N2O was withdrawn, during continued meperidine infusion, cardiac output and stroke volume increased, while peripheral resistance remained low. Coronary vasodilation was noted when meperidine was added to N2O, and persisted when N2O was withdrawn. In the pulmonary circulation a different response was found. Here, no effects were observed when meperidine was added to N2O, while pressure and resistance decreased when N2O was withdrawn and meperidine continued. PMID- 2244449 TI - The effect of bambuterol (carbamylated terbutaline) on plasma cholinesterase activity and suxamethonium-induced neuromuscular blockade in genotypically normal patients. AB - Bambuterol (the bisdimethylcarbamate prodrug of terbutaline) is a new bronchodilator with a prolonged duration of action due to its inhibition of plasma cholinesterase during metabolism. The effect of bambuterol on suxamethonium-induced neuromuscular blockade was studied in 10 patients undergoing elective laparotomy. Thirty mg of bambuterol was given 2 h before anaesthesia, which was performed with thiopentone, fentanyl, halothane and nitrous oxide in oxygen. Neuromuscular function was monitored using supramaximal train-of-four stimulation of the ulnar nerve and a force displacement transducer. Suxamethonium 1 mg.kg-1 was given i.v. for endotracheal intubation. Plasma cholinesterase activity was measured before and after intake of bambuterol and during anaesthesia. The results from the 10 patients were compared with those of 41 patients not given bambuterol but otherwise studied during the same conditions. Following bambuterol, all patients had a significant decrease of plasma cholinesterase activity (P less than 0.001) and the suxamethonium-induced blockade was 3-4 times prolonged compared to patients not given bambuterol (P less than 0.001). Five patients with very low plasma cholinesterase activity developed a long-lasting phase II block. PMID- 2244450 TI - The effect of bambuterol on plasma cholinesterase activity and suxamethonium induced neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase. AB - Bambuterol is a new bronchodilator which is also a reversible inhibitor of plasma cholinesterase. In patients with normal plasma cholinesterase genotype, bambuterol prolongs suxamethonium-induced neuromuscular blockade. In the present study, we investigated the interaction of bambuterol and suxamethonium in nine patients heterozygous for abnormal plasma cholinesterase during anaesthesia with fentanyl, thiopentone, halothane and nitrous oxide in oxygen. The patients (seven E1uE1a and two E1uE1s) were given 20 mg of bambuterol orally 2 h before anaesthesia. Suxamethonium 1 mg.kg-1 was given for tracheal intubation. The neuromuscular function was monitored using train-of-four (TOF) stimulation of the ulnar nerve and a force displacement transducer. Plasma cholinesterase activity decreased in all patients following bambuterol (P less than 0.001). In patients with genotype E1uE1a, median time to 90% recovery of twitch height and TOF ratio greater than or equal to 0.7 (37.5 min) was prolonged compared to 28 E1uE1a patients not treated with bambuterol (14.0 min) (P less than 0.001). Four of these patients developed a phase II block apparently not correlated to plasma cholinesterase activity. In the E1uE1s; patients, full recovery was seen after 22.0 and 31.4 min, respectively. It is concluded that in patients heterozygous for abnormal plasma cholinesterase, bambuterol 20 mg taken 2 h before anaesthesia causes a 2-3 times prolongation of the neuromuscular blockade following suxamethonium 1 mg.kg-1 and in some patients a phase II block. PMID- 2244451 TI - Neuroleptic malignant syndrome and malignant hyperthermia susceptibility. PMID- 2244452 TI - Distant effect of a nuclear disaster? PMID- 2244453 TI - Legislation in the field of human reproduction. PMID- 2244454 TI - ACTA sixty years ago. Goodbye to nineteen-thirty. PMID- 2244455 TI - The therapy of assisted conception and legislation in Iceland. PMID- 2244456 TI - Outcome of pregnancy in one Norwegian county 3 years prior to and 3 years subsequent to the Chernobyl accident. AB - Pregnancy outcome was studied in a county in Norway 3 years prior to and 3 years subsequent to the Chernobyl nuclear plant accident on 26th April 1986. More detailed analyses have been performed for the 12 months prior to and subsequent to the accident. A significant increase in the spontaneous abortion rate the first year after the accident was followed by a slight decrease during the second and third years, but figures were still higher than the period prior to the accident. The rate of legal abortions was unchanged. During the entire observation period the number of births increased continuously, with the exception of a decrease in the last 2 months of 1986 and the first month of 1987. A higher incidence of spontaneous abortions was found for pregnancies conceived during the first 3 months after the accident. This increase in the spontaneous abortion rate is noteworthy, and more especially its long-term persistence, which cannot be the result of external radiation. The internal radiation from food polluted by radioactive fallout is a possible explanation. Changes in nutrition in order to avoid polluted food may also be of importance. PMID- 2244457 TI - When does external cephalic version succeed? AB - From 1984 to 1987, 300 pregnant women with fetal malpresentations underwent an attempt at external cephalic version (ECV) during the last trimester. A consecutive analysis of factors associated with successful version was performed during this period. The final version rate after one or more attempts was 58%, being lower in nulliparous (39%) than in parous women (80%). Multivariate analyses (logistic regression) identified only three significant variables out of 16 with independent power to explain successful version. The overall most important factor was parity (p less than 0.001), followed by fetal presentation (p less than 0.001) and amount of amniotic fluid (p = 0.019). PMID- 2244458 TI - Perinatal and neonatal significance of bacteria-related placental villous edema. AB - In a study of 82 cases of clinical chorioamnionitis in which no antibiotics were administered antenatally, significant villous edema was observed in 51 placentas (62%). Polymorphonuclear leukocyte invasion of the placental plate was found in 53 placentas (65%). The presence of SVE was significantly associated with placental bacterial recovery, occurrence of prolonged rupture of membranes, lower one minute Apgar score, the need for resuscitation and significant neonatal respiratory problems. Findings suggest that bacteria-related placental villous edema can lead to significant perinatal and neonatal morbidities. PMID- 2244459 TI - The effect of delayed pushing in the second stage of labor with continuous lumbar epidural analgesia. AB - We studied primigravid women in spontaneous labor at term and given epidural analgesia. Two hundred such women giving birth in 1983 were compared with similar groups who gave birth in 1985 and 1987 after the introduction of 'delayed pushing' into our labor ward protocol. Four hundred controls were obtained in 1983 and 1985 by selecting from the labor ward register the next normal primigravid woman in spontaneous labor without epidural analgesia. The assisted delivery rate was significantly higher in all three epidural groups than in the controls (p less than 0.001). Among epidural labors, there was no significant difference between 1983 and 1987 in the incidence of rotational or non-rotational forceps, or of cesarean section. In each epidural group, women who waited more than 60 min were less likely to experience a normal spontaneous delivery than were those who did not (p less than 0.001 in 1983; p = 0.006 in 1985 p = 0.035 in 1987). We conclude that to delay pushing beyond 60 min confers no benefit regarding mode of delivery. PMID- 2244460 TI - Acute polyhydramnios in twin pregnancy. A retrospective study with special reference to therapeutic amniocentesis. AB - Acute polyhydramnios in monozygotic twin pregnancy causes severe maternal discomfort and carries a high risk of premature labor. During the years 1980 to 1987, 36 patients with this complication were delivered in Sweden, giving an incidence of 1/20,000 births, or 1/200 twin births. In 18 patients (group A) who were treated with one or more amniotic taps, the delivery was postponed by 2 weeks, as compared with one week in 18 conservatively treated patients (group B). The peri- and neonatal death rate was 47% in group A and 58% in group B. Our own experience is that amniotic taps are safe if the amniotic fluid is removed slowly under prophylactic tocolysis. It gives symptomatic relief to the mother and may postpone labor until the gestational age of the twins is more compatible with survival. PMID- 2244461 TI - Oxytocin and prolactin levels in breast-feeding women. Correlation with milk yield and duration of breast-feeding. AB - The aim of the present study was to examine suckling-related plasma levels of oxytocin and prolactin in early and established lactation and to correlate hormone profiles to success of lactation performance. Fifty-five primiparous women participated in the study. From each, 18 blood samples were drawn in connection with breast-feeding on day 4 post partum and after 3-4 months. Oxytocin and prolactin levels were determined with radio-immunoassay. Basal levels of both hormones were significantly higher 4 days post partum than 3-4 months later and after weaning. Basal prolactin levels fell significantly within 24 h of weaning. Oxytocin and prolactin levels rose in response to breast-feeding -an effect which persisted during the lactation period. The suckling-induced release of prolactin--but not that of oxytocin--was related to basal hormone levels. Basal as well as stimulated oxytocin levels obtained 4 days and 3-4 months post partum correlated significantly, indicating that each woman has an individual, characteristic level of this hormone. Milk yield did not correlate with oxytocin or prolactin levels, but prolactin levels recorded 3-4 months post partum did correlate with the remaining period of breast-feeding. In addition, mothers who breast-fed exclusively 3-4 months post partum had significantly higher oxytocin and prolactin levels than those who gave supplementary feed. There was a significant correlation between oxytocin levels at 4 days and birth weight of the infant. PMID- 2244462 TI - Altered ciliary substructure in the endosalpinx in women using an IUCD. AB - Fallopian tube segments were removed from 20 women undergoing sterilization by laparoscopy or laparotomy. Ten of these patients used an intrauterine contraceptive device (IUCD). The other 10 had used neither IUCD nor oral contraceptives and served as controls. The ciliary ultrastructure was examined by light- and transmission electron microscopy. The IUCD users had a significantly reduced ciliary length and less well oriented cilia, as compared with the control group. Also, the proportion of cilia with a ciliary crown structure was significantly smaller in IUCD users than in the non-users. The mechanism that may cause these alterations and their putative consequences are discussed. PMID- 2244463 TI - Plasma levels of cholecystokinin and gastrin during the menstrual cycle and pregnancy. AB - The objective of the present study was to measure plasma levels of cholecystokinin (CCK-8 and CCK-33,39) as well as of gastrin during the menstrual cycle and pregnancy. Cholecystokinin and gastrin levels were measured by radioimmunoassay. Before being assayed for cholecystokinin, plasma samples were submitted to HPLC which allowed separation of gastrin and cholecystokinin as well as between CCK-8 and CCK-33,39. Fasting CCK levels were 5.2 +/- 0.6 and 7.1 +/- 0.9 pM during the follicular and luteal phases of the menstrual cycle, respectively. The difference was significant (P less than 0.05). CCK levels were 8.7 +/- 1.2, 10.1 +/- 1.6 and 10.4 +/- 1.2 pM during the first, second and third trimester, respectively. CCK levels during pregnancy were significantly higher than during the menstrual cycle. The ratio between CCK-33,39 and CCK-8 appeared to increase during pregnancy. Gastrin levels remained unchanged during the menstrual cycle and pregnancy. The role of the high levels of cholecystokinin may be to stimulate the exocrine and endocrine pancreatic function during pregnancy. Furthermore, since cholecystokinin inhibits gastric emptying, it may play a role in the sickness of early pregnancy. PMID- 2244465 TI - Cyclic changes of the functional ovarian compartments: echographic assessment. AB - Using bidimensional echography, 25 normal ovulatory cycles were evaluated. The following parameters were assessed: 1) ovarian volume, 2) volume of the dominant follicle, 3) corpus luteum volume, 4) residual follicular volume, and 5) stromal volume. Ovarian volume and dominant follicle volumes reached their maximum on day -1: 11.68 +/- 2.87 ml and 3.60 +/- 1.20 ml respectively. The maximum stromal volume was seen during the follicular phase: 7.98 +/- 2.29 ml. In the dominant ovary the maximum corpus luteum volume was observed on day +1 and the maximum stromal volume on day +7 (8.64 +/- 2.53 ml). In the contralateral ovary, the stromal volume did not show significant changes. The residual follicular volume in both ovaries diminished gradually from the early follicular phase except for a slight postovulatory rise. In this study, normal values during the ovulatory cycle were obtained as indicated above. The use of bidimensional echography in the diagnosis of functional disorders of the ovary is stressed. PMID- 2244464 TI - The effect of the anti-progestin mifepristone (RU 486) on plasma prostaglandin metabolite levels in early pregnancy and its influence on pregnancy termination. AB - The effect of a single dose of RU 486 (600mg) on prostaglandin metabolite levels has been studied over a 48 h period in 20 women undergoing medical termination of early pregnancy. The results were compared with controls of similar gestation who were treated surgically. The mean (SD) PGEM levels at 0 and 48 h in the RU 486 group were 13.7 (2.7) and 13.2 (2.2) pg/ml respectively, which was not significantly different from the values of 11.7 (1.1) and 11.3 (0.4) pg/ml measured in the control patients. Similarly the mean (SD) PGFM values of 22.3 (14.7) and 17.0 (7.2) pg/ml at 0 and 48 h were not significantly different from the corresponding control values of 21.9 (13.8) and 23.8 (7.2) pg/ml. In 10 of the study patients, there were no significant changes in PGEM and PGFM concentrations prior to and at 4, 24 and 48 h after RU 486 administration. Although all pregnancies were successfully terminated with the combination of RU 486 and subsequently a vaginal pessary containing PGE1, no stimulation of prostaglandin production could be demonstrated. PMID- 2244466 TI - Prostaglandins--a role in adhesion formation. An experimental study. AB - The effect of intraperitoneal application of prostaglandins F2 alpha and E2 on adhesion formation was studied in the rat after traumatizing to the uterine serosa. Prostaglandins applied locally were found to increase intraperitoneal adhesion formation at the injury site, in comparison with controls. The effect of intraperitoneal application of prostaglandins F2 alpha and E2 on fibroblastic proliferation was examined in vitro, by fibroblastic cell culture of rat kidney, human kidney and human prepuce. No direct effect of prostaglandins on fibroblast proliferation could be demonstrated. It is concluded that prostaglandins play an important role in the process of adhesion formation. This effect is not related to fibroblast proliferation. PMID- 2244467 TI - Vaginal agenesis and congenital adrenal hyperplasia. Psychosocial sequelae of diagnosis and neovagina formation. AB - Eleven patients with Mayer-Rokitansky-Kuster syndrome (MRK) and 7 patients with adrenogenital syndrome (CVAH) were interviewed and tested pre- and postoperatively. MRK subjects were operated on with a modified Vecchietti procedure, CVAH subjects underwent genitoplastic and clitoroplastic operation. Psychosocial sequelae of and coping with malformation and treatment were assessed with semistructured interviews and the Giessen test. Anatomical and functional results of the vaginoplastic operation were excellent, and sexual satisfaction correlated with coping. 7/11 MRK patients were capable of good to fair adaptation to the malformation, whereas CVAH patients suffered severe distortions of body image. The malformation caused narcissistic damage in all cases. Circumstances of diagnosis, prevailing defense mechanism and consequences for counselling are discussed. PMID- 2244468 TI - Normal umbilical artery Doppler sonography does not exclude fetal distress. AB - Umbilical artery Doppler sonography is advocated as a method for fetal surveillance. Two cases of fetal distress caused by fetal anemia of non-immune origin are presented. In both cases a normal pulsatility index of the umbilical artery was found. It is emphasized that normal umbilical artery Doppler sonography does not exclude fetal distress. PMID- 2244469 TI - Treatment with the fibrinolytic inhibitor tranexamic acid--risk for thrombosis? PMID- 2244470 TI - Oral contraceptives and premenopausal breast cancer. PMID- 2244472 TI - Electrostimulation of the pelvic floor in female urinary incontinence. PMID- 2244471 TI - Antiprogesterone steroid RU486. Pharmacokinetics and receptor binding in humans. PMID- 2244473 TI - Carbohydrate metabolism of rats with biliary obstruction. AB - Carbohydrate metabolism of rats with obstructive jaundice caused by bile duct ligation was studied by intravenous glucose tolerance test (IVGTT) and by liver perfusion. The altered levels of carbohydrate-metabolizing enzyme were examined in relation to the glucose metabolism of the cholestatic rats. In the IVGTT, the rate of fractional glucose removal was increased with increases in plasma insulin and glucagon and with a decrease in non-esterified fatty acid. In liver perfusion, neither the glucose uptake nor insulin extraction by the whole liver of icteric rats was different from the control. The increased rate of glucose removal in IVGTT may be due to enhanced glucose utilization by peripheral tissues resulting from hypersecretion of insulin. In liver perfusate supplemented with glucose, a decrease in the glucose uptake per unit liver weight was observed in relation to the lowered glucokinase activity. Formation of glycogen from glucose and of glucose from lactate was also impaired, indicating inhibition of the gluconeogenic system or relative hyperfunction of the glycolytic system, which may further contribute to the reduction in glycogen content. These metabolic disorders correlated well with the changes in activities of key carbohydrate metabolizing enzymes, which showed a characteristic pattern consistent with the loss of differentiated hepatic functions. Uptake of glucose and its conversion to glycogen were reduced in the cholestatic liver in close association with altered activities of some of related enzymes. However, due to increased utilization by the peripheral tissues, the total amount of glucose utilized in the whole rat was not reduced. PMID- 2244474 TI - Cell kinetic analysis of brain tumors using the monoclonal antibody Ki-67: in vitro and in situ study. AB - Ki-67 is a commercially available mouse monoclonal antibody (MoAb), which reacts with a nucleolar antigen (the Ki-67 antigen) expressed in proliferating eukaryotic cells. The author examined the precise localization of the Ki-67 antigen in C-6 cells using immunohistochemical and immunoelectron microscopic methods and estimated the proliferative activity of human brain tumors in situ. Positive nucleoplasmic reactions (early G1 phase) and nucleolar staining (late G1 phase) were observed. The cells showed very weak positive reactions in only one or two nucleoli (S phase) and multiple spicule reactions in the nucleoplasm (G2 phase). During the mitotic phase, the Ki-67 antigen was stained on the surfaces of all chromosomes and finely dispersed in the cytoplasm. By immunoelectron microscopic study, positive reactions were observed on the granular and dense fibrillar components. Therefore, the Ki-67 antigen seems to participate in the processing and assembly of preribosomal particles. In human brain tumors, the Ki 67 score (positive cells/total neoplastic cells), ranging 0 to 36.7%, correlated well with the histopathological grade of malignancy of the tumor. These findings suggest that immunohistochemical staining with the MoAb Ki-67 can be used as a convenient procedure for the simple evaluation of the proliferative activity of brain tumors. PMID- 2244475 TI - Fetal calf serum increased the zona pellucida penetrability of rat oocytes matured in vitro. AB - We examined the effect of fetal calf serum (FCS) on meiotic division, subsequent fertilization, and first cleavage to the 2-cell stage of rat oocytes during in vitro maturation. FCS had no effect on the nuclear progression from dictiate to metaphase of the second maturation in vitro and, FCS had no effect on the first cleavage to the 2-cell stage of fertilized oocytes. However, FCS efficiently increased penetration rate of oocytes and shortened the time required for dissolution of the zona pellucida by alpha-chymotrypsin. These results showed that FCS did not affect cytoplasmic maturation necessary for oocytes to develop to the 2-cell stages. We found that FCS only affects the zona pellucida and does not affect the nucleus or cytoplasm of rat oocytes. FCS may prevent hardening of the zona pellucida. PMID- 2244476 TI - Synergistic antiproliferative effect of the combination of natural human tumor necrosis factor-alpha and natural murine interferon-alpha/beta against colon-26 adenocarcinoma hepatic metastases in a murine model. AB - To prevent the development of hepatic metastases after surgery for colorectal cancer, it is important to inhibit the growth of any micrometastases which occur during the operation. We used a hepatic metastasis model in mice to investigate the effects of combination therapy with natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural murine interferon-alpha/beta (nMuIFN-alpha/beta). Decreased formation of hepatic metastases by murine colon-26 carcinoma was recognized following a single injection of nHuTNF-alpha, nMuIFN-alpha/beta, or both. These inhibitory effects were synergistic. NK activity was also measured, because notaral lerller cells not only have an anti-tumor effect but are also a representative of the host immune system. Both nHuTNF-alpha and nMuIFN-alpha/beta were able to activate NK cells, and the combination of the cytokines more significantly augmented NK activity. The in vivo elevation of NK activity induced by nHuTNF-alpha, nMuIFN-alpha/beta, or their combination may be one of the mechanisms of their antiproliferative effect on experimental hepatic metastases of murine colon-26 carcinoma. PMID- 2244477 TI - A new open reduction treatment for congenital hip dislocation: long-term follow up of the extensive anterolateral approach. AB - Congenital hip dislocation, which is conservatively unmanageable, has usually been treated using open reduction. However, a long-term follow-up study of the results suggests that this procedure is unsatisfactory. Since 1973, Tanabe has used a new open reduction procedure that circumferentially dissects the joint capsule and produces sufficient concentric reduction of the femoral head in the acetabulum immediately after the surgery. Fifty-six children (65 hips) from the age of 1 to 3 years were treated by this procedure, and fifty-one of them were clinically and roentgenographically followed up from 6.3 to 12.4 years after the surgery. At the final follow-up session, all children had grown to be over 9 years of age, and no patient had clinically significant symptoms. According to Severin's classification, 33 hips were rated in Group I, and 14 hips in Group II. Another 10 hips were in Group III, and one hip was in Group IV. The incidence of avascular necrosis was 5.2 per cent. These data suggest that our procedure is more useful than the previous ones. PMID- 2244479 TI - Antioxidants in therapy and preventive medicine. PMID- 2244478 TI - Extracellular-superoxide dismutase, distribution in the body and therapeutic applications. PMID- 2244481 TI - Regulation of lipid peroxidation by glutathione and lipoic acid: involvement of liver microsomal vitamin E free radical reductase. PMID- 2244480 TI - The role of vitamin E in the hepatotoxicity by glutathione depleting agents. PMID- 2244482 TI - Antioxidant properties of vitamin E and membrane permeability in human fibroblast cultures. PMID- 2244483 TI - Vitamin E and tumor growth. PMID- 2244484 TI - The role of superoxide dismutase (SOD) in preventing postischemic spinal cord injury. PMID- 2244485 TI - Abnormal susceptibility to lipid peroxidation of plasma LDL and its prevention by alpha-tocopherol during experimental cholestasis in the rat. PMID- 2244486 TI - Effects of vitamin E treatment in cholestatic children. PMID- 2244487 TI - Efficacy of vitamin E as a drug in inflammatory joint diseases. PMID- 2244488 TI - Vitamin E and correlated antioxidants: a gamma radiolysis study. AB - gamma irradiations of Vit.E-Vit.C aerated ethanolic solutions have been performed for several ratios (Vit.E)/(Vit.C) between 0.1 and 50. The obtained results show that Vit.C is able to regenerate Vit.E from its oxidized radical, this regeneration being total for a ratio (Vit.E)/(Vit.C) greater than or equal to 27 in our conditions of irradiation. The ratio (Vit.E)/(Vit.C) seems to be the main factor of this synergestic effect towards peroxyl radicals scavenging. PMID- 2244489 TI - Ascorbate: the most effective antioxidant in human blood plasma. AB - Ascorbate is the only endogenous antioxidant in plasma that can completely protect the lipoproteins from detectable peroxidative damage induced by aqueous peroxyl radicals and the oxidants released from activated PMNs. In contrast to aqueous oxidants, lipid-soluble peroxyl radicals unsparingly induce detectable peroxidative damage to plasma lipids. However, under these conditions, too, ascorbate appears to belong to the first line of antioxidant defense. Our findings strongly suggest that pathologically relevant lipid hydroperoxide formation consequent to acute or chronic leukocyte activation can be prevented by ascorbate supplementation, provided no free metal catalysts are present. Ascorbate should prove very helpful in the treatment and prevention of diseases and degenerative processes caused by oxidative stress. PMID- 2244490 TI - Radical chemistry of flavonoid antioxidants. PMID- 2244491 TI - SOD in rat models of shock and organ failure. PMID- 2244492 TI - Selenium and oxidant injury in patients with cystic fibrosis. PMID- 2244494 TI - Protection by seleno-organic compound, Ebselen, against acute gastric mucosal injury induced by ischemia-reperfusion in rats. PMID- 2244495 TI - Biological activities and clinical potential of Ebselen. PMID- 2244493 TI - Selenium and glutathione peroxidase activity in diploid human fibroblasts: their effects against H2O2 or UVB induced toxicity. PMID- 2244496 TI - Glutathione level in mice brain after testosterone administration. PMID- 2244497 TI - Prostaglandins, glutathione metabolism, and lipid peroxidation in relation to inflammation in bovine mastitis. PMID- 2244498 TI - Sulfur containing compounds as antioxidants. AB - Several sulfur containing antioxidants have been used for therapeutic use as hepatoprotectors and radioprotectors. In particular the dithiolthione SULFARLEM, used as anticholestatic drug for more than 40 years, is shown to be antioxidant; preliminary pharmacokinetic data in man are presented, and hepatoprotective and radioprotective effect in mice are demonstrated. PMID- 2244499 TI - Zinc--a redox-inactive metal provides a novel approach for protection against metal-mediated free radical induced injury: study of paraquat toxicity in E. coli. AB - The essential mediatory role of copper and iron in a variety of free radical induced injuries, including paraquat-induced biological damage has been recently demonstrated. It was postulated that these transition metals undergo cyclic redox reactions, and serve as centers for repeated production of hydroxyl radical, which are the ultimate deleterious agents. Additionally, we had presented evidence indicating efficient protection against paraquat toxicity by agents commonly employed (chelators, chemical scavengers and protecting enzymes). In this study we have used the E. coli model in order to develop a new approach for protection against paraquat-induced metal-mediated cellular injury. It entails the administration of excess zinc (up to 50 fold over copper), which results in an inhibition of the toxic effect of paraquat. Lineweaver- Burk analysis demonstrates the competitive mode of this inhibition. The suggested mechanism involves the displacement of the redox-active copper (or iron) from its binding site and by this diverting the site of repeated production of free radicals. Thus, use of redox-inactive metals, which possess high similarity of their ligand chemistry, to that of iron and copper but are of relative low toxicity by themselves, should be considered for intervention in paraquat toxicity and in other metal-mediated free radical-induced injurious processes. PMID- 2244500 TI - High molecular weight forms of deferoxamine: novel therapeutic agents for treatment of iron-mediated tissue injury. PMID- 2244501 TI - Oxygen toxicity: role of hydrogen peroxide and iron. PMID- 2244502 TI - Antioxidant properties of an antiischaemic agent: trimetazidine. PMID- 2244503 TI - Oxidative damage in chronic heart failure: protection by captopril through free radical scavenging? AB - The pathogenesis of heart failure is not yet fully understood. In animal models there is some evidence to suggest a role for free radicals (FRs). We have investigated malondialdehyde - LM in plasma of patients with heart failure and found it to be raised when compared to controls. We present data to show that Captopril, a drug with an ACE inhibitory effect is a FR scavenger both in vitro and ex-vivo in patients with heart failure. PMID- 2244504 TI - Comparison of antioxidant and prooxidant activity of various synthetic antioxidants. PMID- 2244505 TI - The protective role of superoxide dismutase during activation of ribonucleotide reductase. PMID- 2244506 TI - Antioxidant effects in radioprotection. PMID- 2244507 TI - Nuclear glutathione transferases which detoxify irradiated DNA. PMID- 2244508 TI - Urinary biomarkers in radiation therapy of cancer. PMID- 2244509 TI - Redox parameters associated to cytotoxic and antitumor activities in the series of antitumor drugs ellipticines and derivatives. PMID- 2244510 TI - Peroxidase induced metabolism and lipid peroxide scavenging by antitumor agents. PMID- 2244511 TI - Reduction of toxicity and increase of antitumor effect of adriamycin by N-acyl dehydroalanines, a new family of free radical scavengers. PMID- 2244512 TI - Are oxygen radicals responsible for the acute cardiotoxicity of doxorubicin? PMID- 2244513 TI - Influence of selenium on lipid peroxidation and cardiac functions in chronically adriamycin-treated rats. PMID- 2244514 TI - Improvement of ischemic and postischemic mitochondrial function by deferrioxamine: the role of iron. PMID- 2244515 TI - Allopurinol in ischemia--reperfusion injury of heart. PMID- 2244516 TI - Effect of superoxide dismutase on the autoxidation of hydroquinones formed during DT-diaphorase catalysis and glutathione nucleophilic addition. PMID- 2244517 TI - Antilipoperoxydant effect of trimetazidine in post ischaemic acute renal failure in the rat. PMID- 2244518 TI - Reperfusion injury and renal metabolism: the temporal relationship between oxidative stress and functional change. PMID- 2244519 TI - Iron redistribution and lipid peroxidation in the cold ischaemic kidney. PMID- 2244520 TI - Ischemia-reperfusion injury and free radical involvement in gastric mucosal disorders. PMID- 2244521 TI - Zinc-carnosine chelate compound (Z-103) attenuates acute gastric mucosal injury induced by ischemia-reperfusion in rats. PMID- 2244523 TI - Antioxidant therapy in hematological disorders. PMID- 2244522 TI - Effect of the platelet-activating factor (PAF) antagonist, BN 52021, on free radical-induced intestinal ischemia-reperfusion damage in the rat. PMID- 2244524 TI - The adult respiratory distress syndrome (ARDS) and oxidative stress: therapeutic implications. PMID- 2244525 TI - Antioxidant activity in fetal and neonatal lung. PMID- 2244526 TI - Pro- and anti-oxidant factors in rat lung cytosol. PMID- 2244527 TI - Oxidants, joint inflammation and anti-inflammatory strategies. AB - In summary, we support the hypothesis that the rheumatoid knee is subjected to repeated hypoxic reperfusion injury. Moreover, we speculate that oxidative damage induced as a consequence of hypoxic reperfusion injury leads to the synthesis of intracellular stress proteins. In certain individuals this triggers an autoimmune response which might explain the persistance of the rheumatoid disease process. This gives scope for novel therapeutic approaches in the future development of anti-inflammatory agents. PMID- 2244528 TI - Antioxidant therapy in neurological disorders. PMID- 2244529 TI - Free radicals and trials of antioxidant therapy in muscle diseases. PMID- 2244530 TI - Parkinson's disease and Alzheimer's disease: neurodegenerative disorders due to brain antioxidant system deficiency? PMID- 2244531 TI - Targeting SOD by gene and protein engineering and inhibition of oxidative stress in various diseases. PMID- 2244532 TI - Protein oxidation and proteolytic degradation. General aspects and relationship to cataract formation. AB - 1) Intracellular proteins are subject to oxidative and photooxidative denaturation. 2) Proteolytic systems recognize and selectively degrade oxidatively denatured, and photooxidatively denatured proteins. By degrading mildly denatured proteins these proteolytic systems prevent further oxidative/photooxidative damage which could otherwise result in the formation of cross-linked (undigestible) proteins, or protein fragments with toxic biological activities. Proteolytic systems also provide amino acids for the synthesis of new (replacement) proteins. 3) A 700,000 dalton neutral endoproteinase, which we have called macroxyproteinase or M.O.P., appears to be mostly responsible for the degradation of oxidatively denatured proteins. M.O.P. has been shown to function in red blood cells and in the eye lens, and appears to also exist in many other mammalian cell types. 4) Cataract is a disease associated with aging, and with photooxidative denaturation (and cross-linking) of lens crystallins and other proteins. 5) Both cataract and aging of lens cells are associated with declining proteolytic capacity and diminished antioxidant protection. 6) Lens aging and in vivo photooxidative stress can cause opacity ("cataract"), cross-linking of crystallins, and diminished proteolytic capacity. 7) High levels of dietary ascorbate increase ascorbate concentrations in lens tissue, and are associated with greater resistance of lens proteins and lens proteolytic enzymes to oxidative/photooxidative stress in vitro. PMID- 2244534 TI - Free radicals and antioxidants in the pathogenesis of eye diseases. AB - There is fairly convincing evidence that free radical mechanisms are involved in the pathogenesis of cataracts and uveitis and that antioxidants may be protective. Studies on retinal degeneration are almost entirely limited to dietary manipulation of vitamins C and D. Unfortunately, antioxidant properties are not easily isolated from other metabolic effects of vitamins. Cataracts, uveitis, and retinal degeneration cause nearly one-third of all blindness. The evidence that free radical mechanisms are important in the pathogenesis of these diseases is compelling incentive to encourage more extensive and detailed investigation. PMID- 2244533 TI - Reactivity of active centre analogues of Cu2Zn2 superoxide dismutase. AB - Active centre analogues of Cu2Zn2 superoxide dismutase were devised and successfully employed. Emphasis was placed on the flexible nature of the superoxide mimicking compounds. Di-Schiff-bases proved most appropriate to fulfil these requirements. Both structural and functional aspects of the copper binding centre of the intact enzyme were met by these complexes. Nanomolar concentrations of copper coordinated in these complexes were sufficient to inhibit the K3CrO8 induced chemiluminescence identical to the reaction of Cu2Zn2 superoxide dismutase. PMID- 2244535 TI - Singlet oxygen-induced damage to rat lenses in vitro: protection by anisyldithiolthione. PMID- 2244536 TI - Dermatologic antioxidant therapy may be warranted to prevent ultraviolet induced skin damage. PMID- 2244537 TI - Antioxidant and prooxidant effects of the antipsoriatic compound anthralin in skin and subcellular fractions. PMID- 2244538 TI - Antioxidant treatment in experimental thermal injury. PMID- 2244539 TI - Rationale for antioxidant therapy in pancreatitis and cystic fibrosis. AB - The overlapping features of the acquired diseases acute pancreatitis and chronic pancreatitis on the one hand, and of chronic pancreatitis and pancreatic involvement in the congenital condition cystic fibrosis on the other, suggest that the basic mechanism of pancreatic injury may be the same in each illness. We propose that pancreatic oxidant stress is the common denominator and, furthermore, that this is facilitated by a shortfall of micronutrient antioxidants in the face of heightened free radical activity through different sources. If so antioxidant supplements should alleviate symptoms. This deduction was supported by an exploratory dose-seeking study that spanned five years in 20 patients with recurrent (non-gall stone) acute or chronic pancreatitis and confirmed by a 20-week double-blind placebo-controlled crossover trial of the successful combination (daily doses of 600 micrograms organic selenium, 0.54 g vitamin C, 9000 IU B-carotene, 270 IU vitamin E and 2 g methionine) in a further 20 cases. A randomised trial of glutathione precursors, given intravenously for 24 hours after admission in patients with a first attack of acute pancreatitis, is in progress. Long-term trials of oral antioxidant formulas are planned in patients with cystic fibrosis. PMID- 2244541 TI - SOD mimicking properties of copper (II) complexes: health side effects. PMID- 2244540 TI - Lipid peroxidation levels and antioxidant activities of blood plasma in parturients and new-born infants immediately after normal delivery. PMID- 2244542 TI - Radiation recovery agents: Cu(II), Mn(II), Zn(II), or Fe(III) 3,5 diisopropylsalicylate complexes facilitate recovery from ionizing radiation induced radical mediated tissue damage. PMID- 2244543 TI - Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. AB - The copper binding tripeptide, glycyl-L-histidyl-L-lysine [GHK:Cu(II)] has a plethora of biological effects related to the wound healing process. The presence of iron complexes in damaged tissues is detrimental to wound healing, due to local inflammation, as well as microbial infection mediated by iron. To test if the wound healing properties of GHK:Cu(II) are due to an affect on iron metabolism, we examined the effects of GHK:Cu(II) on iron catalyzed lipid peroxidation. GHK:Cu(II) inhibited lipid peroxidation only if the iron source was ferritin. Whereas GHK:Cu(II) inhibited ferritin iron release it did not exhibit significant superoxide dismutase-like or ceruloplasmin-like activity. We propose that GHK:Cu(II) binds to the channels of ferritin involved in iron release and physically prevents the release of Fe(II). Thus, a biological effect of GHK:Cu(II), possibly related to wound healing, may be the inhibition of ferritin iron release in damaged tissues, preventing inflammation and microbial infections. PMID- 2244544 TI - Vitamin E in biological systems. AB - The evidence is increasing that free radical reactions are implicated in the development of cell damage and degenerative disease. Results of animal and human studies have demonstrated that vitamin E and the other antioxidants have a significant role in preventing or minimizing peroxidation damage in biological systems. As we await results of additional human studies, there is sufficient evidence to suggest that adequate antioxidant defense by vitamin E and the other antioxidants can provide protection from the increasingly high levels of free radicals present in the environment due to current lifestyles and the rising concentration of environmental pollutants. PMID- 2244546 TI - Routine neonatal circumcision. PMID- 2244545 TI - 'Gracias, Doctor'. PMID- 2244547 TI - Streptococcal pharyngitis. PMID- 2244548 TI - Controversies in the treatment of streptococcal pharyngitis. AB - An increasing number of cases of sore throat caused by group A beta-hemolytic streptococci occur with concomitant colonization by organisms that may "protect" the streptococci through beta-lactamase inactivation of penicillin at the site of infection. The failure of penicillin to eradicate many of these bacteria, which include Staphylococcus aureus, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and a multitude of pharyngeal anaerobes, may help to explain why penicillin is sometimes ineffective for acute and recurrent group A streptococcal infections. Therapeutic alternatives currently include cephalosporins, erythromycin, rifampin combined with penicillin, amoxicillin/clavulanate potassium and others. PMID- 2244549 TI - Lymphoma presenting as a periorbital tumor. AB - Lymphoma is a common tumor of the periorbital region. Facial radiographs may show a soft tissue mass. Radiologic differential diagnosis of orbital masses is difficult. Computed tomographic scanning with intravenous contrast medium is useful in diagnosing and staging neoplasms in this area. PMID- 2244550 TI - Metoprolol for aggressive behavior in persons with mental retardation. AB - Persons with mental retardation sometimes exhibit behaviors that are difficult to control. Use of neuroleptic medications may be limited by side effects or ineffectiveness. Beta blockers such as propranolol and metoprolol have been shown to decrease aggressive and impulsive behaviors in some patients with mental retardation. PMID- 2244551 TI - Postexposure prophylaxis. The U.S. Preventive Services Task Force, Washington, D.C. PMID- 2244552 TI - Infectious mononucleosis in older adults. AB - Infectious mononucleosis as a manifestation of primary Epstein-Barr virus infection occurs uncommonly in adults over age 40. While fever is almost universal, older patients with the disease often present without lymphadenopathy, pharyngitis, splenomegaly, lymphocytosis or atypical lymphocytes. Jaundice and hepatomegaly occur more commonly in older patients than in adolescents and create diagnostic confusion. Often, infectious mononucleosis in this age group is confused with lymphoma, leukemia or biliary obstruction, or is classified as "fever of unknown origin." PMID- 2244553 TI - Seafood safety. PMID- 2244554 TI - NIAAA issues report on screening for alcoholism. PMID- 2244555 TI - Corticosteroid therapy for AIDS-associated PCP. PMID- 2244556 TI - Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). AB - In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244557 TI - Angiographic progression to total coronary occlusion in hyperlipidemic patients after acute myocardial infarction. POSCH Group. AB - The progression of coronary artery stenosis to total occlusion was assessed in 413 hyperlipidemic patients with a previous myocardial infarction. Coronary angiograms were recorded at baseline, 3 (n = 312), and 5 years (n = 248) after initial study and analyzed by 2 independent readers. There were 177 (43%) patients with 1-, 130 (31%) with 2-, and 61 (15%) with 3-vessel disease (greater than or equal to 50% diameter narrowing), whereas 45 (11%) did not have significant disease within a major coronary vessel at baseline. A new finding of total occlusion occurred in 4% (30 of 748) and 7% (40 of 605) of major coronary artery segments at 3 and 5 years, respectively. The risk of progression to total occlusion was higher if the initial stenosis was greater than 60% compared to lesions less than or equal to 60% both at 3 years (19 of 143 = 13% vs 11 of 605 = 2%; p less than 0.001) and 5 years (27 of 91 = 30% vs 13 of 514 = 3%; p less than 0.001). The frequency of occlusion was highest for the right coronary artery by 5 years (18 of 167 = 11% for right vs 8 of 225 = 4% for circumflex vs 14 of 213 = 7% for left anterior descending coronary arteries; p less than 0.02). Clinical and laboratory data revealed that myocardial infarction was associated with a new total occlusion in 23% of patients (7 of 30) at 3 years and in 64% (25 of 39) at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244558 TI - Ability of calcium-entry blockade by felodipine to disclose different pathogenetic mechanisms behind hyperventilation-induced myocardial ischemia in men. AB - To verify that myocardial ischemia occurring during either the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 +/- 31 at baseline to 168 +/- 55 mm Hg x beats/min/100 at the onset of ST-segment depression; p less than 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 +/- 24 at baseline to 158 +/- 46 mm Hg x beats/min/100 at the onset of electrocardiographic changes; p less than 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 +/- 35 at baseline vs 102 +/- 27 mm Hg x beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244559 TI - Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease. AB - To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Women's Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis. PMID- 2244560 TI - Usefulness of tomographic thallium-201 imaging for detection of restenosis after percutaneous transluminal coronary angioplasty. AB - The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization. PMID- 2244561 TI - Coronary artery disease in the octogenarian: angiographic spectrum and suitability for revascularization. AB - The angiographic findings of 84 consecutive octogenarians presenting with symptoms of coronary artery disease (CAD) were examined to determine the extent of CAD as well as suitability for both coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). The frequency of 0-, 1-, 2 , and 3-vessel and left main CAD was 7, 14, 21, 57 and 13%, respectively. Based on angiographic criteria, 69 of 78 patients (88%) with significant CAD had suitable coronary anatomy for CABG. Only 24 patients (31%) had coronary anatomy amenable to PTCA. CABG was performed in 19 patients with an operative mortality of 16% and major complication rate of 37%. PTCA was performed in 12 patients with a clinical success rate of 83%, mortality of 8% and major complication rate of 8%. It is concluded that in octogenarians with CAD, cardiac catheterization will often reveal coronary anatomy that is suitable for CABG but less suitable for PTCA. The morbidity and mortality associated with these interventions are high. PMID- 2244562 TI - Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease. AB - There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease. PMID- 2244563 TI - Sudden death behind the wheel from natural disease in drivers of four-wheeled motorized vehicles. AB - The heart was studied in 30 persons who died suddenly from natural causes in the driver's seat of an automobile, truck or bus. Twenty had cardiac arrest while driving and the other 10 while sitting in the driver's seat of a parked vehicle. Of the 20 drivers, 16 died from atherosclerotic coronary artery disease (CAD): 12 (75%) had minor collisions and 4 did not. Of the 16 with fatal CAD, an average of 2.3 +/- 0.8 of the 4 major coronary arteries were narrowed greater than 75% in cross-sectional area (CSA) by plaque; of 668 five-mm segments of the 4 major (right, left main, left anterior descending, left circumflex) coronary arteries in 13 of these 16 cases, 27 (4%) were narrowed 96 to 100% and 127 (19%) were narrowed 76 to 95% in CSA by plaque. The remaining 4 drivers died from noncoronary conditions: aortic rupture associated with the Marfan syndrome in 1; cardiac sarcoidosis in 1; thoracic aortic dissection in 1; and severe mitral regurgitation from infective endocarditis, which had healed in 1. The other 10 persons were found dead in the driver's seat of a parked vehicle and 8 of them had fatal CAD. Of the 8 CAD victims, an average of 2.5 +/- 1.2 of the 4 major coronary arteries was narrowed greater than 75% by plaque; of the 283 five-mm segments of coronary arteries in 7 of the 8 cases, 44 (16%) were narrowed 96 to 100% and 69 (24%) were narrowed 76 to 95% in CSA by plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244564 TI - Changes in plasma free fatty acids and glycerols during prolonged exercise in trained and hypertensive persons taking propranolol and pindolol. AB - The extent to which lipolysis is attenuated during prolonged submaximal exercise during beta blockade was determined in 12 normotensive endurance-trained and 12 hypertensive sedentary men using nonselective drugs with and without intrinsic sympathomimetic activity (ISA). Initially, subjects performed a graded treadmill test to determine maximal oxygen uptake (VO2max). This was followed by 2-hour walks at 25 and 45% of the subject's VO2max under each of 3 treatments: pindolol (ISA), propranolol (non-ISA) and placebo. The distribution of medication was randomized and double blinded. Blood samples taken at rest and every 30 minutes during the 2-hour walks were analyzed to determine the concentrations of free fatty acids (FFA) and glycerol. On the basis of the respective changes in FFA, glycerols and the respiratory exchange ratio, beta-adrenergic blockade did not attenuate lipolysis in the untrained hypertensive subjects when compared with the placebo administration. However, beta blockade did demonstrate a tendency to attenuate lipolysis in the trained, normotensive subjects when compared with results after placebo administration. This was particularly evident at 30 minutes of exercise, when both glycerol and FFA concentrations were not increased above resting values under both conditions of beta blockade. No differences between pindolol and propranolol were observed. Therefore, a beta-blocking agent with ISA properties appears to have no clear benefit with respect to lipid metabolism during low and moderate intensity exercise. Furthermore, these data demonstrate that beta blockade does not inhibit exercise-induced lipolysis at low and moderate intensities of exercise as formerly believed, and is unlikely to be the cause of fatigue normally observed during work in patient populations taking beta blocking medication. PMID- 2244565 TI - Effects of renin inhibition in systemic hypertension. AB - The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension. PMID- 2244566 TI - Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. AB - To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation. PMID- 2244567 TI - Use of auscultation to follow patients with mitral systolic clicks and murmurs. AB - Mitral systolic clicks and murmurs together with associated symptoms constitute a major reason for cardiologic referral. Although echocardiography with Doppler study enables characterization of the mitral valve apparatus and quantification of regurgitation, its use has resulted in an overemphasis of the technical diagnosis of mitral valve prolapse and an undervaluation of diagnosis based on physical examination. To determine the clinical significance of an auscultatory classification of mitral systolic clicks with or without precordial systolic murmurs, 1 consultant's medical records of 291 patients with these signs were reviewed. Based on initial auscultatory findings, patients were divided into: (1) single or multiple apical systolic clicks with no murmur (n = 99); (2) single or multiple apical systolic clicks and a late systolic murmur (n = 129); and (3) single or multiple apical clicks and an apical pansystolic murmur or murmur beginning in the first half of systole (n = 63). The average duration of patient follow-up was 8 years (range 1 to 30). The prognosis was excellent for patients from all 3 classes. Two cardiac-related deaths occurred: 1 each from classes 1 and 2. Mitral valve surgery was performed in 3 class 2 patients (2%) and in 2 class 3 patients (3%). No patients developed endocarditis during follow-up. Palpitations, with varying anxiety overlay, constituted a major indication for cardiologic referral in all 3 classes. Auscultatory findings were valuable to the physician for explanation and relief of patient anxiety. For patient management, use of an auscultatory classification may be preferable to the technically generated term "mitral valve prolapse." PMID- 2244568 TI - Quantitative analysis of ventricular late potentials in healthy subjects. AB - Signal averaging is a technique that improves the signal-to-noise ratio. Obscuring random noise, it allows the detection of low-amplitude wave forms in the terminal portion of the QRS complex, also known as ventricular late potentials. A higher incidence of arrhythmic events has been found in patients with abnormal ventricular late potentials after an acute myocardial infarction. Few studies have been conducted in healthy subjects to assess normal values. Sixty-one healthy subjects were enrolled in our study (33 men and 28 women). The results (mean +/- standard deviation) are as follows: duration of the filtered QRS (QRS duration) was 95 +/- 10 ms; duration of the low-amplitude signals in the terminal portion of QRS less than 40 microV (LAS less than 40) was 32 +/- 8 ms; and root-mean-square voltage in the last 40 ms (RMS - 40) was 33 +/- 16 microV. A significant difference was noted in QRS duration between men and women (98 +/- 11 vs 92 +/- 6 ms, p = 0.006); no difference was found in LAS less than 40 (31 +/- 8 vs 34 +/- 8 ms) and in RMS-40 (36 +/- 17 vs 30 +/- 13 microV). QRS duration confidence limits of 95% were less than or equal to 114 ms for the total group, less than or equal to 120 ms for men and less than or equal to 104 ms for women. Normalization of QRS duration for height (normal value less than 66 ms/m) eliminated any difference between men and women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244569 TI - Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques. PMID- 2244570 TI - Stepped-down therapy versus intermittent therapy in systemic hypertension. PMID- 2244571 TI - A 50-year-old useful report on coronary risk for noncardiac surgery. PMID- 2244572 TI - Perioperative myocardial ischemia and infarction. PMID- 2244573 TI - Ages at death and sex distribution in age decade in fatal coronary artery disease. PMID- 2244574 TI - Relation of angiographic detected intracoronary thrombus and silent myocardial ischemia in unstable angina pectoris. PMID- 2244575 TI - Effects of intracoronary ergonovine on the contralateral coronary artery in patients with atypical chest pain. PMID- 2244576 TI - Hypercholesterolemia after cardiac transplantation in children. PMID- 2244577 TI - Atrioventricular nodal reentry and dual atrioventricular node physiology in patients undergoing accessory pathway ablation. PMID- 2244578 TI - Significance of exercise-induced left hemiblock. PMID- 2244579 TI - Effects of noninvasive ambulatory blood pressure measuring devices on blood pressure. PMID- 2244580 TI - Training for intermediate clinical lipid specialists. PMID- 2244581 TI - Ventricular arrhythmias during spontaneous ischemic ST-segment depression. PMID- 2244582 TI - The best antiarrhythmic agent will be a lipid-lowering agent. PMID- 2244583 TI - Blood vascular network of the rat lymph node: tridimensional studies by light and scanning electron microscopy. AB - Many aspects of the blood vascular network of the lymph node are unknown, and others need confirmation. We have studied the blood vasculature of rat peripheral lymph nodes by means of carbon perfusion and vascular cast corrosion techniques. At the hilus of the node, an artery gives off arterioles running in medullary cords towards the cortex. Some reach the peripheral cortex directly, branching there into slender cortical vessels. Other arterioles enter the periphery of the deep cortex units, and then head towards the peripheral cortex. Upon reaching it, they curve part way above the center of the deep cortex units and provide slender branches to the overlying peripheral cortex. Dense plexuses of capillaries arise from arterioles in the medullary cords, in the periphery of the deep cortex units, and in the outermost stratum of the extrafollicular zone of the peripheral cortex. In the cortex, the draining high endothelial venules are restricted to the extrafollicular zone and to the periphery of the deep cortex units. At the cortico-medullary junction, these peculiar venules transform into regular medullary venules which form the hilar veins. In contrast, the folliculo-nodules and center of the deep cortex units are little vascularized by a loose capillary network, while no vessels occur in the subsinus layer. These features of the node vascular network are of interest in relation to the node architecture. PMID- 2244584 TI - The human rhombencephalon at the end of the embryonic period proper. AB - The human rhombencephalon at 8 postovulatory weeks (stage 23) is described and illustrated for the first time with the aid of silver-impregnated sections and graphic reconstructions. The motor and sensory trigeminal nuclei were among those studied, and the latter was found to be almost contiguous to the dentate nucleus. Fibers to the principal sensory nucleus join the mesencephalic trigeminal tract, which also seems to be connected with the motor fibers. Fine fibers from the sensory root join the tractus solitarius, which appears to receive connections from the facial, glossopharyngeal, and vagal nerves. Main and accessory abducent nuclei are evident. A part (the Kappenkern des Facialisknies) of the nucleus funiculi teretis is particularly prominent. The presence of the pyramidal decussation during the embryonic period is noted for the first time. The arrangement of nuclei and tracts at 8 weeks is shown to be closely similar to that present in the newborn, and it is likely that the rapid growth of the rhombencephalon during the embryonic period proper is associated with correspondingly early functional activity. PMID- 2244585 TI - Ultrastructural morphology and relaxin immunolocalization in giant trophoblast cells of the golden hamster placenta. AB - Relaxin immunoreactivity was previously demonstrated in three cell types within the hamster placenta; fetal primary and secondary giant trophoblast cells (GTCs) and maternal endometrial granulocytes. The objectives of the present research were to examine the ultrastructure of the GTCs and identify the intracellular relaxin storage site. Primary GTCs, first present on day 8 of gestation, were characterized by numerous polyribosomes and large heterogeneous cytoplasmic inclusions suggesting phagocytic activity. Primary and secondary GTCs from days 10, 14, and 15 of gestation contained numerous polyribosomes, mitochondria with tubular cristae, and extensive Golgi complex, and abundant rough endoplasmic reticulum, all characteristics of a cell actively involved in protein synthesis. Membrane-bound secretory granules were not present. Relaxin was immunolocalized within the Golgi complex of primary and secondary GTCs using the avidin-biotin peroxidase method. Following differential centrifugation of hamster placental homogenates and radioimmunoassay (RIA) of subcellular fractions, the majority of relaxin immunoactivity was detected in the postmicrosomal fraction; however, the majority of relaxin immunoactivity from similarly treated pig corpora lutea was present in the mitochondrial/granule fraction. These data indicate that hamster placental relaxin is not stored in membrane-bound secretory granules but is contained within the extensive Golgi complex of the GTC. PMID- 2244586 TI - Distribution of 3H-proline within transseptal fibers of the rat following release of orthodontic forces. AB - Maxillary right first molar teeth of rats were tipped mesially with an orthodontic appliance for 2 weeks (experimental group), 3H-proline was injected, and orthodontic forces were removed 6 hr later (time 0). The contralateral molar teeth of treated (internal control group) and age- and weight-matched untreated animals (external control group) were also studied. Diastemata were created between the molar teeth by the orthodontic appliance, and transseptal fibers between first and second (P less than 0.001) and second and third molars (P less than 0.005) were significantly lengthened as compared to external and internal controls at time 0. Diastemata between molar teeth were closed 5 days after removal of orthodontic force. Transseptal fibers adjacent to the source of the orthodontic force (mesial region) had the highest mean number of 3H-proline labeled proteins at time 0 and at all times following removal of the force (P less than 0.001), and had the highest rate of labeled protein removal (P less than 0.001). Half-lives for removal of 3H-proline-labeled transseptal fiber proteins were significantly greater in mesial and distal regions and significantly less in middle regions of experimentals than in corresponding regions of external controls (P less than 0.001). These data suggest the following: 1) transseptal fibers adjust their length by rapid remodeling in regions experiencing a tensile force; 2) collagenous protein turnover within the middle third of the transseptal fibers is more rapid subsequent to release of orthodontic force than during normal physiologic drift, suggesting that this region adapts rapidly to changes in adjacent tooth position and that these fibers do not play a significant role in relapse of orthodontically relocated teeth; and 3) significant differences in turnover rates of 3H-proline-labeled transseptal ligament proteins of external and internal control quadrants suggest that tooth movement produces both local and systemic effects on collagenous protein metabolism. PMID- 2244587 TI - Craniofacial alterations following electrolytic lesions of the trigeminal motor nucleus in actively growing rats. AB - The objective of this study was to define further the role of the trigeminal motor nucleus (TMNu) in the postnatal ontogeny of the mammalian craniofacial skeleton. To that end, 42 male Sprague-Dawley rats underwent stereotaxic surgery at 40 days of age; 21 received small electrolytic lesions to their left-side TMNu (lesioned group) while 21 had TMNu stimulation with no actual electrolytic lesion produced (sham group). Seven rats from each group were killed at 28, 56, and 84 days postoperative to analyze trigeminal motoneuron (TMNe) count, masticatory muscle weight, and osteological growth vector data. At all three time periods, lesioned animals showed significant differences 1) between the surgery and nonsurgery sides, and 2) from sham animals. However, sham animals also demonstrated significant between-side differences for medial pterygoid muscle weight (56 days), mandibular height (28 and 56 days), and mandibular length data (84 days); these data suggested that even relatively slight damage to TMNe can create morphological changes within the craniofacial complex. Snout deviation in a lesioned rat towards the opposite side from all other lesioned animals was correlated with unique damage to its pontine reticular formation; this suggested that the observed morphological alterations of the craniofacial complex may have been due not only to TMNu damage, but also to changed expressions of the masticatory central pattern generator (CPG). Morphological alterations of the craniofacial skeleton resulting from lesions to the TMNu were likely due to changed neuromuscular activity patterns of the masticatory muscles and their biomechanical effects upon bone. PMID- 2244588 TI - Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast. AB - To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion. PMID- 2244589 TI - Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. AB - In a prospective study of 148 consecutive breast adenocarcinomas, proliferative indices of the same surgical tumor sample were performed by immunohistologic staining (Ki67 index) with the use of the Ki67 monoclonal antibody, which binds to a nuclear antigen only expressed in cycling cells, and by flow cytometry derived S-phase fraction (SPF). Measurable Ki67 and SPF indices were obtained in 142 cases and 99 cases, respectively, and in 96 cases by both methods. In aneuploid tumors, a significant but low (P less than 0.05, r = 0.3) relationship was observed between Ki67 index and SPF. When compared with clinical, pathologic, and biochemical parameters these two proliferative indices were shown to be associated with nuclear grading and mitotic index. Additionally, correlations were observed between Ki67 index and node involvement (P less than 0.02) and between SPF and estrogen receptors (P = 0.002). These results show that (1) proliferative indices are obtained in 96% of surgical samples with Ki67 versus 67% with SPF and that (2) Ki67 index and SPF may provide complementary data with respect to prognosis. PMID- 2244590 TI - Cytologic features of poorly differentiated 'insular' carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy. AB - The authors report on the cytologic features of six cases of poorly differentiated "insular" carcinoma (IC) of the thyroid, a recently described variety of thyroid tumor intermediate between well-differentiated and anaplastic neoplasms. It is characterized by trabecular and/or alveolar growth patterns, merging with follicular areas, and by the absence of pleomorphism in the tumor cells. Fine-needle aspiration biopsy (FNAB) materials (both smears and cell-block preparations) from six patients were reviewed after the diagnosis of IC was confirmed on the surgical specimen. The following cytologic features were consistently found: high cellularity and necrotic background; low grade of atypia; trabeculae and/or clusters, possibly associated with microfollicles, of cells with poorly defined cytoplasm; and cytoplasmic vacuoles containing thyroglobulin. Nuclear inclusions and grooving of the nuclear surface were additional features. Preoperative diagnosis suggestive of IC might be of value for planning surgical treatment and subsequent therapy. PMID- 2244591 TI - Diagnosis and localization of prostate carcinoma by fine-needle aspiration cytology and correlation with histologic whole-organ sections after radical prostatectomy. AB - Twenty-nine patients with clinical stage T1-2, NO, MO prostate carcinoma were treated by retropubic radical prostatectomy. Diagnosis was made by fine-needle aspiration biopsy from six to eight separate sectors of the prostate. At the time of biopsy, diagrams of the palpated organ were drawn, depicting the location of the lesion and the site of each biopsy. Without the examiners' knowledge of cytologic data, extirpated prostate glands were examined with whole organ histologic sections, and carcinomas were scored according to the method of Gleason. The location and extent of all typical and malignant foci were mapped on a standard diagram. The results of preoperative cytologic examination were compared with postoperative histopathologic findings, showing a tendency toward underestimation of both the extent and degree of differentiation of the carcinomas during cytologic examination. In no case were these parameters overestimated during cytologic examination. The Gleason score correlated well with the presence of capsular and seminal vesicle invasion. PMID- 2244592 TI - Ki-M6 immunostaining in routinely processed sections of reactive and neoplastic human lymphoid tissue. AB - A monoclonal antibody, termed Ki-M6 (CD68), which shows a restricted reactivity to cells of the monocyte/macrophage system, has been evaluated primarily with the use of cryostat sections. In this study the authors could assess that the Ki-M6 antibody recognizes a fixation-resistant epitope in most human macrophages. The Ki-M6 immunoreactivity with monocyte/macrophage-related cells was established by testing on routinely processed samples of reactive and neoplastic lymphoid tissues; it was compared with the staining for vimentin (V9) and S-100 protein antibodies, with visualization of the stationary elements of lymphoid tissues, with the aim of establishing its value in the study of the nonlymphoid microenvironment. The Ki-M6 antibody reactivity could be achieved with Bouin fixed, paraffin-embedded tissue sections, without any proteolytic treatment, with the use of the avidin-biotin complex (ABC) method, especially after overnight incubation time at 4 degrees C. Some reduction in antigenic reactivity was observed in B5- or formaldehyde-fixed samples. The antibody reacted with macrophages of all different lymph node compartments; a broad reactivity against cells of macrophage lineage, including multinucleated giant cells, was observed in epithelioid granulomas. Ki-M6-positive cells other than classic macrophages were the so-called "plasmacytoid T-cells" and cells displaying elongated cytoplasms with fibroblastic-like features. Granulocytes, follicular dendritic reticulum cells, and interdigitating reticulum cells did not reveal any reactivity with Ki-M6 antibody. In malignant lesions, neoplastic cells of follicular and diffuse B- and T-cell lymphomas, including large cell non Hodgkin's lymphomas, and Reed-Sternberg cells of Hodgkin's disease were negative in all cases studied. This study shows that Ki-M6 seems to be another anti macrophage-specific antibody that reacts, in routinely processed tissue sections, with tissue macrophages but not with accessory cells. Thus, it may be a valuable addition to vimentin and S-100 protein antibodies for investigation of the microenvironmental organization of lymphoid tissues both in normal and neoplastic conditions. PMID- 2244593 TI - Quality assurance in gynecologic cytology. What is practical? AB - The quality of gynecologic cytology has been questioned in the last two years. This author's hospital laboratory has a sizable outpatient gynecologic cytology and biopsy practice from which data have been obtained in several different quality assurance projects. In this article the author analyzes those data with respect to detection of false negative cytology screening errors, specimen sampling errors, precision in cytology and biopsy interpretation, and productivity of quality assurance methods. Sampling errors in obtaining cytology specimens are a major problem to be addressed by cytology quality assurance. The most sensitive and efficient method for detection of false negative cytologic results in this laboratory was rescreening of previous negative Papanicolaou's (Pap) smears in patients presenting for the first time with an abnormal Pap smear. Data indicate that the currently mandated requirement for rescreening 10% of a laboratory's negative Pap smears should be reconsidered and rescinded in certain circumstances. PMID- 2244594 TI - Strategy for breakpoint cluster region analysis in chronic myelocytic leukemia in a routine clinical laboratory. AB - Despite the increasing reliance on breakpoint cluster region (bcr) determinations in diagnosis of chronic myelocytic leukemia (CML), few reports have dealt with the practical aspects of specimen analysis. In the setting of a routine molecular diagnostics laboratory, samples from 68 patients with active CML were evaluated for bcr rearrangements, with the use of a variety of enzymes and two probes. The data have been used to develop an efficient strategy for bcr screening and breakpoint determination. Screening with the universal bcr (UBCR) probe on Xba I and BgI II digests yielded bcr rearrangements in 100% of the Ph1-positive patients and three of the seven Ph1-negative patients, giving bcr analysis a sensitivity of 100%. A single-enzyme screen using the UBCR probe would have resulted in a false negative rate of 10%. The false negative rate was determined during the breakpoint site analysis from additional digests hybridized to both the 3' and UBCR probes. The false negative rate for the 3' probe was 26.5%, because of deletions or 5' rearrangements. The method of breakpoint site determination was dependent on screening results. In 78% of cases, one additional hybridization with two enzyme digests was required. During breakpoint site analysis, a rare false negative result was also demonstrated with Bam HI and Eco RI. This screening strategy has made bcr analysis competitive with cytogenetic analysis at the authors' institution; although turnaround time may be slightly longer, bcr analysis can yield information (such as detecting bcr-positive/Ph1 negative patients and determining breakpoint site) that cannot be obtained by cytogenetics. PMID- 2244595 TI - Angiotropic lymphoma with histologic features of neoplastic angioendotheliomatosis presenting with predominant respiratory and hematologic manifestations. Report of a case and review of the literature [corrected]. AB - Neoplastic angioendotheliomatosis (NAE) is a rare fatal disease characterized by widespread intravascular proliferations of neoplastic mononuclear cells. Clinically, dermatologic and bizarre neurologic manifestations usually predominate. The origin of the neoplastic cells remains still undetermined. The authors report a patient with NAE peculiar with respect to the following points: (1) the patient predominantly manifested respiratory symptoms and hematologic findings and lacked cutaneous or neurologic manifestations; and (2) immunohistochemical and molecular genetic studies showed the B-cell nature of the neoplastic cells, although previous cases with predominant respiratory or hematologic manifestations were reported to be of endothelial origin. Despite the rarity, this type of NAE or angiotropic [corrected] lymphoma should be recognized because it is easily confused with other disorders, particularly vasculitis or thrombotic thrombocytopenic purpura. PMID- 2244596 TI - Multiple myeloma and acute megakaryoblast leukemia in spent phase polycythemia vera. AB - The spontaneous and simultaneous occurrence of multiple myeloma and megakaryoblast leukemia with myelodysplastic features in a case of spent phase polycythemia vera is well documented. In support of the morphologic characteristics of the bone marrow, immunocytologic studies show proliferation of monoclonal plasma cells and megakaryoblasts. The cytogenetic findings of 20q- and unbalanced t(1;7) are consistent with myelodysplastic and leukemic transformation of the bone marrow. These transformations expand observations on variable and spontaneous lineage commitments as the consequence of alterations of the hematopoietic stem cell clone. These data are in support of the changing insights in hematopoiesis as a process of ordered commitment of the stem cell with sequential lineage potentials. PMID- 2244597 TI - Concomitant neurocysticercosis and brucellosis. AB - A young Mexican woman had headache and left arm weakness develop shortly after immigrating to the United States. A solitary cerebral cysticercus was found at surgery, but, instead of the expected finding of clear fluid, the cyst contained pus from which Brucella melitensis was cultured. Although the patient had no signs or symptoms suggestive of brucellosis, agglutination studies revealed IgM and IgG antibodies consistent with active brucellosis. Clinicians should be alert to the possibility of multiple infections in immigrants from countries where parasites and bacteria that are uncommon in the United States are endemic. PMID- 2244598 TI - The maturation of aspiration cytology. PMID- 2244599 TI - Reappraisal of preoperative coagulation testing. PMID- 2244600 TI - Detecting hemoglobin Bart's on cord blood. PMID- 2244601 TI - Lymphocytes in breast tissue. PMID- 2244602 TI - Reliability of rapid urease test. PMID- 2244603 TI - Histologic diversity of malignant melanoma. PMID- 2244604 TI - Heparin's effect on blood gas analysis. PMID- 2244605 TI - Duplicate publication and related problems. PMID- 2244606 TI - Cigarette smoking and adolescent pregnancy. Double trouble. PMID- 2244607 TI - Trends in teenage smoking during pregnancy. Washington State: 1984 through 1988. AB - Smoking rates in the United States have decreased since 1963, but this trend is less apparent in adolescents, especially girls. Using data on birth certificates from 1984 through 1988, we analyzed smoking trends during pregnancy in teenagers in Washington State. There was a small but significant increase in the overall smoking prevalence during pregnancy between 1984 (32%) and 1988 (37%). Smoking rates varied by mother's age, race and ethnicity, marital status, and prenatal care. Whites had the highest smoking prevalence, and native Americans showed the largest increase in smoking prevalence over time. In the 5 years studied, unmarried pregnant teenagers had a smoking prevalence of 42.8%, compared with a rate of 31.7% in married teenagers. Compared with other studies of smoking rates in nonpregnant teenagers, pregnant teenagers in Washington State had a much higher smoking prevalence than their nonpregnant peers, and the differences between these two groups did not appear to diminish over time. This study suggests that there is little movement toward meeting the 1990 Health Objectives for the Nation regarding smoking in Washington State teenagers who become pregnant. PMID- 2244608 TI - Midfacial hypoplasia associated with long-term intubation for bronchopulmonary dysplasia. AB - Six preterm infants with bronchopulmonary dysplasia were nasotracheally intubated for 68 to 243 days. Gestational age at birth ranged from 24 to 35 weeks. Endotracheal tube size was changed to account for growth and varied from 2.5 to 4.0 mm. These infants developed features of midfacial hypoplasia, namely, depressed nasal bridge, small-tipped nose, long philtrum, underdeveloped malar areas, and carplike mouth. These features have not been associated with long-term intubation in premature infants. We suggest that features of prolonged nasotracheal intubation, such as direct compression by the tube and the method of tube fixation, decreased air flow through the developing nares and sinuses and reduced faciomuscular activity, resulting in the observed midfacial hypoplasia. The degree to which growth corrects these deformations is unknown. PMID- 2244609 TI - Cystic Fibrosis Foundation guidelines for patient services, evaluation, and monitoring in cystic fibrosis centers. The Cystic Fibrosis Foundation Center Committee and Guidelines Subcommittee. PMID- 2244610 TI - Impetigo. Current etiology and comparison of penicillin, erythromycin, and cephalexin therapies. AB - We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection. PMID- 2244611 TI - Concurrent habits. What would Linus do with his blanket if his thumb-sucking were treated? AB - Thumb-sucking and object attachment commonly occur during childhood. Object attachment is usually harmless, but thumb-sucking can lead to complications when chronically practiced by older children. Effective thumb-sucking treatment is available, but to my knowledge, it has not been evaluated on thumb-sucking children who are also attached to objects. This study, using a multiple baseline design, shows treatment eliminated thumb-sucking in eight thumb-sucking children with concurrent attachment and that seven of the children subsequently lost interest in their attachment object. PMID- 2244612 TI - Genital and anal conditions confused with child sexual abuse trauma. AB - Examination of a child with genital or anal disease may give rise to suspicion of sexual abuse. Dermatologic, traumatic, infectious, and congenital disorders may be confused with sexual abuse. Seven children referred to us are representative of such confusion. PMID- 2244613 TI - Parenchymal and vascular magnetic resonance imaging of the brain after extracorporeal membrane oxygenation. AB - Three-dimensional (volume) magnetic resonance angiography is a new and noninvasive method for imaging the intracranial vasculature. The combination of magnetic resonance angiography and conventional magnetic resonance imaging was used to evaluate brain parenchyma and vessels in 30 survivors of extracorporeal membrane oxygenation. Magnetic resonance imaging findings were abnormal in 33% of the patients, with no increased frequency of right hemispheric lesions. Magnetic resonance angiography demonstrated good intracranial flow in all infants and demonstrable right internal carotid arterial flow in 35% of those patients with permanent carotid ligation. An abnormal magnetic resonance imaging study was found more often in infants with abnormal predischarge neurologic examination results. These techniques have several advantages over other neuroimaging modalities, including better definition of deep structures, myelin formation, and intracranial vasculature, the absence of bone artifact, and the elimination of catheter or contrast use. PMID- 2244614 TI - Reported practices of pediatric residents in the management of attention-deficit hyperactivity disorder. PMID- 2244615 TI - The use of anatomically correct dolls in the evaluation of sexually abused children. AB - There is confusion and controversy regarding the use of anatomically correct dolls in the evaluation of allegedly sexually abused children. Studies indicate that there is a significant difference between the play behavior of sexually abused children and that of nonabused children when using anatomically correct dolls. Other research suggests that nonabused children are not threatened, sexually stimulated, or excited to aggression by exposure to anatomically correct dolls. These dolls can be used by trained professionals to help make conclusions about a child's background. However, the dolls cannot be used to prove or disprove abuse. PMID- 2244616 TI - Lung function in children following empyema. AB - Spirometry was performed and response to exercise was measured in 15 children following recovery from empyema to evaluate the impact of pleural infection on subsequent lung function. Seven children underwent chest tube drainage; eight did not. The two groups were similar in age (mean +/- SD, 6 +/- 5 years), sex distribution, bacterial pathogen-producing empyema, and age at follow-up evaluation (12 +/- 5 years). Only one child reported recurrent respiratory symptoms. No child had restrictive spirometric changes (total lung capacity, less than 80%; vital capacity, less than 80% predicted) but seven of 15 had a reduced forced expiratory volume in 1 second (less than 80% predicted) or forced expiratory flow during the middle half of the vital capacity (less than 75% predicted), suggesting mild airway obstruction. No child demonstrated reduced exercise tolerance due to restrictive ventilatory limitations. Mild obstructive abnormalities in lung function were identified with equal frequency in children treated with and without chest tube drainage. PMID- 2244617 TI - Newborn screening for sickle cell disease. When is an infant 'lost to follow-up'? AB - Success of programs to screen newborns for sickle cell disease depends on timely follow-up. Education regarding fever and splenic palpation, and initiation of prophylactic penicillin therapy, will reduce morbidity and mortality and should occur prior to 4 months of age. However, contacting parents to permit implementation of care may be difficult, particularly in large urban populations; only nine (36%) of 25 infants recently identified as having sickle cell disease arrived at our institution for initial appointments. Medical providers must be aware of medical and legal obligations related to follow-up of newborns with sickle cell disease to prevent untoward events in "missed cases." PMID- 2244618 TI - Spinal bone mineral density in children aged 5.00 through 11.99 years. AB - Lumbar spine (L-2, L-3, L-4) bone mineral density was measured in 184 healthy boys and girls aged 5.00 through 11.99 years by dual photon absorptiometry. Weight, height, age, triceps skinfold thickness, and midarm circumference were also measured. Weight, height, and age were highly correlated with bone mineral density. In the population studied, a quadratic regression equation using body weight as the independent variable best described bone mineral density: bone mineral density = 0.3209 + [0.0168 (weight)] - [0.0001 (weight2)]. PMID- 2244619 TI - Radiological cases of the month. Retropharyngeal abscess. PMID- 2244620 TI - Radiological cases of the month. Cerebral air embolism. PMID- 2244621 TI - Picture of the month. Protein C deficiency. PMID- 2244622 TI - Resident training in community pediatricians' offices. Not a financial drain. AB - There are numerous disadvantages to teaching ambulatory pediatrics in hospital based clinics. The present study evaluated the economic impact on community pediatricians' practices that served as continuity experience sites for pediatric residents by using an apprenticeship model. The number of patients seen and the dollars billed by the presence of a resident, even though these preceptors provided significantly more supervision to residents than that received by residents in hospital-based clinics. Furthermore, residents billed substantial revenues for preceptor practices. This approach to teaching general pediatrics is economically viable, providing resident stipends are not dependent on fees generated by patient visits. PMID- 2244623 TI - Growth in obese children treated for obesity. AB - This study assesses the growth patterns during a 5-year period in children aged 6 to 12 years treated for obesity using behavioral family-based treatment procedures. Previous studies have suggested a decrease in height velocity after weight reduction, but these results did not consider either the height of the parent or the greater height of obese than nonobese children. Results show that at entry, obese children are taller than their nonobese peers (74th percentile), and that even after 5 years, they remain taller than the norm (65th percentile). Child weight and level of physical maturity accounted for 54% of the variance in predicting baseline height percentile. Entrance height and parental height accounted for 9% of the variance in changes in height percentile, both adjusted for parental height. Weight change did not correlate with growth adjusted for parental height. These results do not suggest that negative effects on height are a long-term side effect of child weight control. PMID- 2244624 TI - Diagnostic aspects and syndromal associations of short trachea with bronchial intubation. AB - Conditions with disproportionately short trachea, with a reduced number of tracheal cartilage rings and a high level of tracheal bifurcation, have been reported. We have seen accidental bronchial intubation in nine patients with short trachea. This risk can be reduced by recognition of conditions associated with short trachea, by awareness that methods for calculating endotracheal tube length from body length can overpredict tube length for patients with short trachea, and when feasible, by use of preintubation chest roentgenograms showing air bronchograms to establish the thoracic level of tracheal bifurcation. Twelve patients with short trachea, four with bronchial intubation, and six conditions not previously associated with short trachea, are reported. Three of the patients also had laryngeal hypoplasia. PMID- 2244625 TI - Case for a National Association of Physicians for the Environment. PMID- 2244626 TI - Occupational risks of thyroid cancer: data from the Swedish Cancer-Environment Register, 1961-1979. AB - Using data from a record-linkage between the Swedish population census of 1960 and the Swedish Cancer Registry, we performed an explorative, hypothesis generating analysis of the incidence of thyroid cancer in 208 occupations and 231 industries. Relative risks were computed with adjustment for age, period of follow-up, and geographic region. A total of 1,230 male and 2,937 female cases of thyroid cancer were reported during 1961-1979 among individuals aged 20-69 years in 1960. As a group, male blue-collar workers had a lower reported incidence than other men. Significantly elevated risks were seen among drivers, pharmacists, workers in the canning and preserving industry, workers in the petroleum industry, and among X-ray operators and laboratory assistants. Horticulture workers, painters in the construction industry, and unskilled manual workers showed decreased risks. PMID- 2244627 TI - Case report of occupational asthma due to palisander wood dust and bronchoprovocation challenge by inhalation of pure wood dust from a capsule. AB - Occupational asthma due to exposure to exotic wood dust and to rosewood (Dalbergia family) has been reported earlier. This paper deals with a case of occupational asthma due to palisander wood dust (Dalbergia nigra) in a joiner who sanded and polished parts of musical instruments. The causal relationship was confirmed by a positive skin reaction to an allergenic preparation and a positive nonimmediate, late asthmatic reaction after inhalation challenge testing with pure palisander wood dust. A method of bronchoprovocation testing with an occupational allergen is presented. It proved to be a practical and advantageous method in its simplicity and single-blind application of placebo. It should, however, be used with great caution, in well-chosen cases in whom nonspecific bronchial reactivity is proved or recorded to be in normal ranges. PMID- 2244628 TI - Congenital malformations and death among the offspring of Danish pharmacy assistants. AB - Congenital malformations, stillbirth, and infant mortality were studied in a cohort of all female pharmacy assistants in Denmark under the age of 40 years who were members of the national union in 1979 to 1984 (4,939). Data on all births and deaths during first year of life during the study period were identified through the national birth register. Information on type of work, exposures, and life-style variables were obtained by postal questionnaires, to which 93% responded. In general, pharmacy assistants had a low frequency of congenital malformation and death among their offspring. Compared with an internal reference group, pharmacy assistants engaged in production or packing of pharmaceutical products experienced an increased prevalence of congenital malformations among their offspring. Working with identification and controls showed a slightly increased risk of death during the first year of life of the children. This could indicate occupational risks, but other explanations cannot be excluded. PMID- 2244629 TI - Occupation and pancreatic cancer risk in Louisiana. AB - To study the relation of occupational exposures and pancreatic cancer, we evaluated data from males (198 cases and 209 controls) participating in a hospital-based case-control study conducted in a high-risk area of Louisiana between 1979 and 1983. The questionnaire obtained information on lifetime occupational history, as well as dietary, smoking, and drinking habits and demographic characteristics. After adjustment for smoking and dietary patterns, white collar occupations showed consistent elevations in risk, whereas associations for other occupations were in general unremarkable. Although not significantly elevated, risks for truck drivers (OR = 1.7) and those with long term employment in machine repair or as mechanics were suggestive (OR = 2.5). No association was found for jobs in oil refining or oil and gas extraction (ORs were 0.5 and 0.4, respectively), although risks were slightly elevated for long term workers in the chemical processing industry (OR = 1.2). While these associations deserve further study, our findings are consistent with results of other studies which do not suggest that occupational exposures are important determinants of pancreatic cancer. PMID- 2244630 TI - Biological monitoring of a worker acutely exposed to MBOCA. AB - A 30 year-old male polyurethane worker was exposed to an accidental spill of 4,4' methylene-bis-2-chloroaniline (MBOCA) at a plant producing MBOCA-cured plastic products. Exposure to MBOCA is significant in that this compound is a known animal carcinogen and a suspected human carcinogen. The employee was sprayed over his upper body and extremities with molten MBOCA while cleaning out a clogged hose from a MBOCA and polymer mixing machine. The subsequent environmental and medical evaluation of this episode included serial urinary MBOCA samples from the worker over a 2 week period to allow the calculation of a biological half-life for this compound. This worker experienced a very high dose of MBOCA as judged by his urinary MBOCA levels (peak value of 1,700 ppb 4 hours after exposure). There were no acute symptoms or other laboratory abnormalities noted. The kinetic evaluation resulted in a biological half-life for MBOCA in urine of approximately 23 hours. Assuming a one-compartment model, approximately 94% of an initial MBOCA dose will be eliminated within four days. This is the first report of kinetic analysis on urinary MBOCA excretion in humans. This information suggests that biological monitoring of the urine MBOCA concentrations in exposed workers may miss peak levels following an acute exposure unless the analyses of the urinary MBOCA are performed in a timely fashion. Recommendations to the company included: 1) installation of a warning system or lock-out device on the mixing machine to prevent the opening of the MBOCA hose prior to the release of pressure; and 2) annual medical surveillance of this individual for bladder cancer with urinalysis and urine cytology. PMID- 2244631 TI - Historical perspectives in occupational medicine. Diatomaceous earth silicosis. PMID- 2244632 TI - Historical perspectives in occupational medicine. Pancoast and the image of silicosis. AB - In the two decades following the First World War, American occupational medicine was consumed in cataloguing the pneumoconioses, and no physician was more prominent than Henry K. Pancoast of the University of Pennsylvania. In a landmark trial following the worst silicosis outbreak in the United States at Gauley Bridge, West Virginia, Pancoast testified for the defense, attributing the disease to tuberculosis. Pancoast was not an isolated commentator, as the prominence of the cases attracted some of the country's leading authorities on occupational medicine. Pancoast's error, as well as the accuracy of some of his colleagues, clarifies an important occupational disease in its epidemic period. There is also a less historically specific exposition of the impact of professional involvement in social policy, liability, and compensation. PMID- 2244633 TI - In memoriam. Norton Nelson, Ph.D. PMID- 2244634 TI - Investigation of excess cancer of other and unspecified sites among chemical workers. PMID- 2244635 TI - The deja vu experience: remembrance of things past? AB - The deja vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical features, and etiology of the phenomenon of deja vu. They also review the different hypotheses on the psychopathogenesis of the deja vu experience and introduce an explanation based on the hologram as a mnestic model. PMID- 2244636 TI - An empirical literature review of definitions of severe and persistent mental illness. AB - Seventeen definitions of the severely and persistently mentally ill have appeared in the literature over the past decade. These definitions have been used by 13 authors to formulate service programs and to estimate the prevalence of serious mental illness in the population. To test the applicability of these definitions, the authors operationalized each definition and applied it to a representative sample of 222 patients receiving services in one of Philadelphia's inner-city neighborhoods. The analysis showed estimates of prevalence of serious mental illness ranging from 4% to 88% of the treated population, depending on the definition applied. The NIMH (1987) definition was representative of the middle range estimates of 45% to 55% arrived at by eight authors. PMID- 2244637 TI - Brainstem auditory evoked response and subcortical abnormalities in autism. AB - Previous studies of the neurobiology of autism that have used the brainstem auditory evoked response have given contradictory results. The authors of this study considered two supplementary aspects; they added an ipsilateral masking procedure, and they compared the results for every subject to the values (corrected for age and sex) of a large number of normal children. Twenty autistic (according to DSM-III-R criteria) and 13 mentally retarded (nonverbal IQ less than 75) subjects were assessed. Eighty percent of the autistic subjects had abnormal interpeak latencies, compared to 15% of the mentally retarded subjects. The I-V and III-V prolonged interpeak latency values were seen only in the autistic subjects. The ipsilateral masking procedure doubled the rate of detection of higher-brainstem abnormalities in the autistic children. PMID- 2244638 TI - The UCLA-University of Utah epidemiologic survey of autism: the etiologic role of rare diseases. AB - Twelve rare diseases known to cause CNS pathology were found in 26 (11%) of 233 autistic probands identified during a recent epidemiologic survey of Utah. These 26 probands had significantly lower mean IQs than the remaining patients (43 versus 60) but similar sex distribution and prevalence of abnormal EEGs and seizures. The rarity and diversity of these 12 diseases make it highly unlikely that they randomly occurred with autism. Their presence in this epidemiologic survey is the most compelling evidence to date to support the hypothesis that different diseases producing different types of CNS pathology can play an etiologic role in autism. PMID- 2244639 TI - Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression. AB - Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings. PMID- 2244640 TI - Outcome of patients with chronic affective disorder: a five-year follow-up. AB - Patients with major depression, mania, or schizo-affective disorder that had been present without remission for 2 years or more at intake (N = 129) were followed prospectively for 5 years, as were 580 patients who had been ill for shorter periods at intake. Despite very substantial durations of episode, three-quarters of the chronic patients recovered, although recovery occurred much later in the follow-up period than it did among the nonchronic patients. Factors associated with recovery were less severe illness at intake, lack of psychotic features, good friendship patterns in adolescence, and, most important, a relatively high maximum level of functioning in the 5 years preceding intake. PMID- 2244641 TI - Late luteal phase dysphoric disorder in young women. AB - The authors determined the prevalence of late luteal phase dysphoric disorder in 217 university women aged 17-29 years. Unaware of the focus on premenstrual syndrome (PMS), the participants rated DSM-III-R symptoms of late luteal phase dysphoric disorder over 90 days. Using a 30% or greater premenstrual change as an index of luteal variation, the authors found that 10 women (4.6%) met the symptom criteria during two menstrual cycles. Compared to 25 young women seeking treatment for PMS who met the same diagnostic criteria, the 10 women from the university sample reported significantly less fatigue and impaired concentration and somewhat less severe depression and overall symptoms. PMID- 2244642 TI - A longitudinal study of psychotropic prescriptions in a teaching nursing home. AB - This study clarifies the methodological pitfalls of using cross-sectional data to characterize episodic and continuous patterns of prescribing psychotropic medications in nursing homes. Although more than half of the residents in a teaching nursing home received a psychotropic drug during their 5 years of residence, less than one-quarter were continuously medicated. The authors conclude that although the rates of psychotropic prescriptions are an important entry point for concerns about quality and appropriateness of psychotropic administration to older nursing home residents, longitudinal studies including the prescribing pattern, indications, and efficacy are needed to determine more clinically meaningful indicators of quality care. PMID- 2244643 TI - Pharmacologic treatment of noncognitive behavioral disturbances in elderly demented patients. AB - Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week randomized, double-blind comparison trial of haloperidol, oxazepam, and diphenhydramine to test the efficacy of these agents in the treatment of clinically significant behavioral disturbances in patients with dementia. All three agents demonstrated modest but significant efficacy as measured by clinician ratings of agitated behavior and activities of daily living. The absolute magnitude of improvement was greater for haloperidol and diphenhydramine than for oxazepam, but differences among groups did not approach statistical significance. Frequencies of acute adverse events during the trial were similar across the drug treatment groups. Although these drugs may differ in terms of long-term safety and efficacy, they appear to be equivalent for short-term management of agitated behavior in severely demented patients. PMID- 2244644 TI - Dyskinetic movements, cognitive impairment, and negative symptoms in elderly neuropsychiatric patients. AB - The presence or absence of tardive dyskinesia, cognitive status, and psychopathology were assessed in a group of elderly male psychiatric patients (N = 49) in a nursing home setting. Twenty-five patients were found to have tardive dyskinesia, which was associated with a greater degree of cognitive impairment and negative symptoms. This finding was not related to obvious macroscopic organic pathologies, which were less prevalent in the dyskinetic patients. In fact, patients with frontal lesions (primarily lobotomies) had a significantly lower prevalence of tardive dyskinesia. PMID- 2244645 TI - Remediation of cognitive deficits in schizophrenia. AB - Studies have suggested that schizophrenia is characterized by an impairment in the dorsolateral prefrontal cortex that prevents learning of some elementary information processing tasks. To test this hypothesis, the authors administered the Wisconsin Card Sorting Test to 16 schizophrenic inpatients with standard instructions and either contingent or noncontingent reinforcement. Performance was markedly impaired under each condition. A second cohort (N = 12) was tested after receiving instructions plus rehearsal and feedback. These subjects' performance was comparable to nonpatient norms and was maintained on a subsequent day. The results indicate that deficits in performance on the Wisconsin Card Sorting Test are remediable, whether or not they are due to neurological impairment. PMID- 2244646 TI - Sudden death from acute cocaine intoxication in Virginia in 1988. AB - A review of medical examiners' autopsy records revealed that in 1988, 33 residents of Virginia died of acute cocaine intoxication. The subjects were 19 to 45 years old; most were men, used cocaine intravenously, and used other toxic substances with the lethal dose of cocaine. PMID- 2244647 TI - Koro: proposed classification for DSM-IV. AB - Koro, a culture-specific disorder consisting of complaints of genital retraction and fear of death associated with genital retraction, has been recognized in Asian cultures in single cases and in epidemic proportions. Koro has been described in non-Asian patients as well, leading to debate concerning the true nature of the syndrome. The authors review past attempts to define and classify koro and present a classification for DSM-IV that they believe could be used to classify other culture-bound syndromes as well. PMID- 2244648 TI - Neuroleptic malignant syndrome associated with withdrawal from carbamazepine. PMID- 2244649 TI - Possible synergistic anticonvulsant effect of propranolol and carbamazepine. PMID- 2244650 TI - Concept of psychological trauma. PMID- 2244651 TI - Limitations of fluoxetine. PMID- 2244652 TI - Fluoxetine and suicidal ideation. PMID- 2244653 TI - Cessation of menses due to perphenazine rather than fluoxetine? PMID- 2244654 TI - Differential diagnosis and treatment of dementia. PMID- 2244655 TI - Effects of personality disorder in depressed patients. PMID- 2244657 TI - Recovery from bereavement after a suicide. PMID- 2244656 TI - Sleep disturbance in PTSD. PMID- 2244658 TI - The Dissociative Disorders Interview Schedule. PMID- 2244659 TI - Overemphasizing diagnostic classification. PMID- 2244660 TI - Report of the APA Task Force on Prevention Research. PMID- 2244661 TI - Morphometric diagnosis of melanocytic skin tumors. AB - Checking consecutively sampled routine sections of 206 melanocytic lesions with a maximum vertical diameter of at least 1 mm (133 benign dermal nevi, 20 Spitz's nevi, 53 primary malignant melanomas), we measured the morphometric features of at least 60 nuclei each from the superficial and the deep dermal tumor portion using a computer-assisted interactive image analysis system. Furthermore we calculated the so-called maturation parameter (MP) in each case as the ratio of the mean nuclear area in the deep portion and the superficial portion. When we compared the results with those obtained in a training set, we found that the lowest evidence for the discrimination of benign and malignant melanocytic lesions resulted from the application of the mean values of the nuclear area in the superficial layer (efficiency = 62.1%). The efficiency was higher when we used the mean values of the nuclear area in the deep layer (96.1%) and the maturation parameter (85.4%). By applying the mean nuclear area in the deep portion and the maturation parameter simultaneously, we gained the highest efficiency, specificity, and sensitivity for the distinction between benign dermal nevi and malignant melanomas (0.968, 0.955, 1) as well as for the distinction between Spitz's nevi and malignant melanomas (0.986, 0.950, 1). Our study shows that morphometry provides reliable diagnostic results in routinely sampled melanocytic skin tumors. PMID- 2244662 TI - Immunohistochemistry of GCDFP-24 and zinc alpha2 glycoprotein in benign sweat gland tumors. AB - The immunohistochemical localization of two other proteins that are present in breast gross cystic disease fluid, GCDFP-24 and zinc alpha 2 glycoprotein (Zn2GP), were studied in normal skin and in 41 benign sweat gland tumors. GCDFP 24 was localized to apocrine glands. There was no staining of eccrine glands or ducts. There was positive staining in the following sweat gland tumors: apocrine hidrocystoma (four of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (six of seven), mixed tumor (one of one), and glandular elements of cylindroma (one of four). No staining for GCDFP-24 occurred among the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), syringoma (eight cases), eccrine spiradenoma (two cases), or clear cell hidradenoma (five cases). Zn2GP was localized to both apocrine glands and eccrine glands. Positive staining was seen in the following SGT: apocrine hidrocystoma (five of five), hidradenoma papilliferum (two of four), syringocystadenoma papilliferum (four of seven), mixed tumor (one of one), cylindroma (one of four), eccrine spiradenoma (two of two), and clear cell hidradenoma (one of five). No staining for Zn2GP was seen in the following SGT: eccrine hidrocystoma (two cases), eccrine poroma (three cases), or syringoma (eight cases). GCDFP-24 appears to be a discriminant of apocrine differentiation and function. Zn2GP was expressed predominantly in tumors of apocrine differentiation. However, it was also expressed in some tumors of eccrine differentiation. PMID- 2244663 TI - Secondary localized amyloidosis in trichoepithelioma. A light microscopic and ultrastructural study. AB - Two trichoepitheliomas with secondary localized amyloidosis were documented in a 74-year-old man. The ultrastructural findings support an origin of amyloid from tumor cells. It is suggested that the occurrence of amyloid is a reflection of the ability of tumor cells to produce an excessive number of tonofilaments from which amyloid is believed to be derived. The intimate spatial association between amyloid and fibroblasts may suggest the existence of some yet undefined functional relationship. PMID- 2244664 TI - Multiple rhabdomyomatous mesenchymal hamartomas of skin. AB - A case of multiple rhabdomyomatous mesenchymal hamartomas is presented. The patient is a black male infant, the product of an uncomplicated term gestation and delivery. At birth, there were numerous polyps distributed over the periorbital and periauricular areas bilaterally. Some appeared fingerlike with constrictions below their tips. Others were branched or globular in shape. These projections showed spontaneous and independent movement, particularly during feedings. On histopathologic examination, the polyps were covered by squamous epithelium and contained normal follicular units. Bundles of skeletal muscle were present in the reticular dermis, extending into the subcutis. Regular cross striations were seen in these muscle fibers. In some specimens, the muscle bundles formed a solid, central core. Skeletal muscle histochemical stains confirmed the presence of both types 1 and 2 muscle fibers. Electron microscopy revealed a normal skeletal muscle banding pattern. This case is the first report of multiple rhabdomyomatous mesenchymal hamartomas of skin. Functional skeletal muscle with spontaneous movement is part of the clinical picture. PMID- 2244665 TI - A review and proposed new classification of benign acquired neoplasms with hair follicle differentiation. AB - A review and proposed new classification of benign acquired neoplasms which differentiate towards hair follicle structures is presented. Seventeen neoplasms are discussed with an in-depth review of the literature. PMID- 2244666 TI - Actinic keratoacanthoma. Speculations on the nature of the lesion and the role of cellular immunity in its evolution. AB - The implications of cytologic atypia, patterns of growth, stromal refractoriness, and immune responses in actinic keratoacanthoma are examined here in a speculative manner with the following conclusion: keratoacanthoma is a generic designation for a spectrum of invasive, keratinocytic hyperplasias. In this context, hyperplasia may affect both genomically normal and abnormal keratinocytes. In keratoacanthoma, it does so indiscriminately. The universality of the process in which both benign and neoplastic clones are affected qualifies as immunostimulation. The affected keratinocytes, regardless of genomic characteristics, extend beyond their sustaining stroma into retinaculum and the basement membrane, as an immunologic barrier, is disrupted. Following a period in which the stroma and the immune response are refractory, one or more clones of keratinocytes are exposed to an immune response. For the adnexal contributions, the eventual encounter with the immune response is brief and short-lived. The fate of these genomically intact cells is predictable: complete regression is the inviolate pathway. For the genomically deranged populace, the results of the encounter are unpredictable and potentially manifold. The options, variably expressed, include regression, spatial progression (expansion in space), and neoplastic progression (expansion in the number and types of neoplastic clones). In some actinic keratoacanthomas, neoplastic clones are represented in either focal or extensive carcinomalike patterns from the inception of the hyperplasia. In them, a potential for neoplastic progressions is inherent. If autonomous, aggressive clones are selected in the progressions, the transition from universal hyperplasia (keratoacanthoma) to malignancy (carcinoma) is effected. In the transition, hyperplastic, genomically intact, follicular keratinocytes are not affected; actinically deranged keratinocytes are. The final pathway for an individual evolving lesion is unpredictable, but in some cases it leads to biologic carcinoma (carcinoma ex-keratoacanthoma). PMID- 2244667 TI - Looking back ... Paul Langerhans, Theodor Langhans, and Carl Touton--contemporary histopathologists. PMID- 2244668 TI - Eruptive vellus hair cyst and steatocystoma multiplex. PMID- 2244669 TI - Eruptive vellus hair cysts. A follicular cyst of the sebaceous duct (sometimes) PMID- 2244670 TI - Congenital rhabdomyomatous mesenchymal hamartoma. PMID- 2244671 TI - Comparison of clinical significance and allergenic cross-reactivity of storage mites Blomia kulagini and Lepidoglyphus destructor in Sweden and Brazil. AB - Comparison of the clinical significance and allergenic cross-reactivity of Blomia kulagini (B. kulagini) and Lepidoglyphus destructor (L. destructor) was made on sera from Sweden and Brazil using the radio-allergo-sorbent test (RAST) and the RAST inhibition technique. RAST-positive sera were obtained from 53 allergic Swedish farmers and 31 allergic subjects from Brazil who were positive to B. kulagini and/or L. destructor. B. kulagini was shown to be a common cause of sensitization especially in Brazil. There was a fairly high correlation between positive RAST results to L. destructor and B. kulagini based on sera from both Sweden and Brazil. The highest RAST scores were found against L. destructor in Swedish sera and against B. kulagini in Brazilian sera. The RAST inhibition studies showed that the L. destructor extract was able to inhibit the B. kulagini system (a positive RAST to B. kulagini allergen disc) in Swedish but not in Brazilian sera. In contrast, the B. kulagini extract was only able to inhibit the L. destructor system in sera from Brazil and not in sera from Sweden. This study shows that results obtained with RAST inhibition are not entirely dependent on the overall specificity of the IgE antibodies in the patient's sera, since the more subtle specificity of the primarily sensitizing allergen will dominate. Thus, conclusions drawn regarding allergenic cross-reactivity are dependent on the populations tested, and conclusions on the existence or absence of cross reactivity, e.g. between two species of mites may be contradictory. PMID- 2244672 TI - Evaluation of immunotherapy-induced changes in specific IgE, IgG and IgG subclasses in birch pollen allergic patients by means of immunoblotting. Correlation with clinical response. AB - Sera from 27 birch pollen-allergic patients who had undergone hyposensitization treatment for 22-41 months were studied by immunoblotting before and after therapy, whereby the levels of IgE, IgG and IgG1-4 antibodies directed against the major allergen Bet v I and minor allergens of birch pollen were monitored. The clinical benefit of immunotherapy (IT) was evaluated using a symptom specific questionnaire. In patients with good clinical response (responders, n = 18), as defined by improvement of symptoms, anti-Bet v I IgE antibodies were found to decrease in 10/18 patients (55.5%), whereas in 6/18 (33.3%) no change and in two cases (11.2%) an increase of specific IgE was observed. In the group of patients with unsatisfactory clinical outcome (non-responders, n = 9), 3/9 patients (33.3%) showed a decrease, 3/9 (33.3%) no change and 3/9 (33.3%) an increase in levels of IgE antibodies directed against Bet v I. In the case of minor allergens, 5/18 responders (27.7%) and 8/9 non-responders (88.8%) showed specific IgE before IT. In the responder group, no increase of specific IgE could be observed after IT. In non-responders, however, an increase of IgE directed against minor allergens was seen in 3/9 patients (33.3%). In all patients, regardless of therapeutical success, IT-induced elevated levels of specific IgG, IgG1 and in particular IgG4 directed against Bet v I were found. Regarding minor allergens, a heterogeneous pattern of IgG responses without significant correlation to clinical benefit was observed. Our results indicate that changes in IgG reactivity patterns against Bet v I and minor allergens, as shown by the immunoblot technique, did not correlate with good or bad clinical outcome. PMID- 2244673 TI - IgE levels in cord blood and at 4-5 days of age: relation to clinical symptoms of atopic disease up to 18 months of age. AB - To evaluate the variation in serum IgE levels during the neonatal period and its relation to the development of atopy, 83 infants with a heredity of atopy were studied with regard to the concentration of IgE in cord blood (CB) and capillary blood on the fourth or fifth day of life. During the neonatal period, the average IgE level remained unchanged in the whole group but there were large individual changes. Among 22 infants with CB-IgE levels greater than or equal to 0.9 kU/l the IgE concentrations in 50% decreased below this value on days 4-5. The correlation between maternal IgE and CB-IgE concentrations (rs = 0.41; P less than 0.001) was interpreted as indicating a probable contamination with maternal blood. This view was supported by the presence of an elevated IgA level and of IgE antibodies against inhalant allergens in 16% of the cord blood samples of which 69% had an IgE level exceeding 0.9 kU/l. It therefore seems preferable to collect the blood samples on the fourth or fifth day. However, in the 74 infants available for atopic classification at 18 months of age, the positive predictive value of IgE determinations was low: on days 4-5 25-38% and in CB 42%. A high CB IgE level may merely be an indication of the mother's atopic state. PMID- 2244674 TI - Temporal association between Der pI exposure, immediate hypersensitivity and clinical severity of eczema. AB - Uncontrolled studies of avoidance of house dust mite (Dermatophagoides pteronyssinus) by atopic subjects have reported clinical improvement in the severity of eczema. The aim of the present study was to examine the temporal relationship between environmental exposure to the major mite allergen (Der pI) and clinical disease severity in children with chronic atopic eczema. Twelve children were identified as being house dust mite-sensitive on the basis of skin prick test and RAST to Der pI. They were examined on two occasions with a median interval of 63 days. Clinical severity of eczema improved in nine children and deteriorated in two children during this period. Der pI concentration in dust from mattresses changed significantly in only three subjects and there was no correlation between changes in clinical severity and changes in environmental Der pI exposure. Change in RAST against Der pI did correlate positively with change in Der pI exposure (rho = 0.56, P less than 0.05) but these changes were not associated significantly with changes in eczema severity or skin test response to Der pI. It is concluded that the observed changes in clinical severity were unlikely to be due to immediate hypersensitivity responses to natural variations in Der pI concentrations in the personal environments of these subjects. PMID- 2244675 TI - Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma. AB - Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects. PMID- 2244676 TI - Abnormal plasma catecholamine levels in severe atopic eczema (AE) PMID- 2244677 TI - [Abuse of cesarean section]. PMID- 2244678 TI - [Purification of residual waters in small communities]. PMID- 2244679 TI - [Dermatologic epidemiology]. PMID- 2244680 TI - [Regeneration of the visual system in the rat. Essay rewarded by the Premio de la Academia Curso 1989]. PMID- 2244681 TI - [The alarming neglect of preventive medicine]. PMID- 2244682 TI - [Experimental organ transplantation (presentation of a book)]. PMID- 2244683 TI - [Epidemiologic method and the health of the community (presentation of a book)]. PMID- 2244684 TI - Re-evaluation of fibroblasts and fibroblast-like cells. AB - Scanning electron microscopic observations of connective tissue cells show a new aspect of the nature of fibroblasts, and the subsequent broad survey of references makes clear that fibroblasts of many tissues have various features which are regarded as atypical of fibroblasts, and at the same time that various connective tissue cells in different organs have features typical of fibroblasts. Both morphological and functional features of fibroblasts are more or less common to those of fibroblast-like cells, and differences among these cells are quantitative rather than qualitative. Therefore, it is almost impossible to set clear-cut criteria for distinguishing genuine fibroblasts from a large population of fibroblast-like cells. The majority of cells sharing features of fibroblasts, if not all, seem to belong to the same population of cells. They are probably adapted to special functional needs in their own micro-environment that are peculiar to local or pathological or experimental conditions. It is proposed to categorize these cells into subtypes depending on their main functions: 1, fibrogenesis; 2, tissue skeleton or barrier; 3, intercellular communication system; 4, gentle contractile machinery; 5, endocrine activity; and 6, vitamin A storing. Re-evaluation of fibroblasts and fibroblast-like cells is required to facilitate their better understanding. PMID- 2244685 TI - Distribution patterns of dendrites in motor neuron pools of lumbosacral spinal cord of the chicken. AB - The morphology of dendritic trees (dendroarchitecture) of motor neurons innervating specific hindlimb muscles (motoneuron pools, MNP) was studied in the chick spinal cord. Motoneurons were labelled by intramuscular injections of horseradish peroxidase conjugated with cholera toxin subunit B. MNPs of posterior iliotibial and femorotibial muscles were located at the dorsolateral part of lateral motor column of lumbosacral segments (LS) 1-4 and 1-3, respectively. Although the dendritic profiles of femorotibialis motoneurons were fewer than those of posterior iliotibialis, these two MNPs had a similar distribution pattern of dendrites. Dendritic profiles were about equally distributed in the gray and white matter. Dendrites from the MNP of posterior iliotibialis radiated in all directions. A large number of dendrites penetrated into the white matter, and some even reached to the subpial regions of the lateral funiculus. One array of dendrites that projected dorsomedialwards extended to the base of the posterior horn. MNPs of both the iliofibularis (LS 4-7) and caudilioflexorius (LS 6-8) had dendritic trees with similar distribution patterns. There were two main arrays of dendritic extensions; one along the dorsal, and another along the ventral border of the lateral motor column. Dendrites from the iliofibularis and caudilioflexorius motoneurons were located more frequently in the white matter than in the gray matter. A large number of dendrites extended in all directions from the MNP of the adductor muscle, which was located in the medial region of lateral motor column of LS 1-2. The distribution of dendrites from a few other MNPs was also examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244687 TI - Generation of GABA-synthesizing nerve cells cultured from embryonic cortex cerebri of mice with and without cell-to-cell contacts. AB - Neuroblasts, growing from cerebral cortices of embryonic mice, Theiler stages 16, 19, 20, 21, 23 and 24 (embryonic days (ed) 10, 11 1/2, 12, 13, 15 and 16) were cultured in plasma clot and serum-containing MEM-medium in whole-mount cultures, suspension cultures or single-cell cultures. In whole-mount cultures, cell connections were preserved, allowing continuity of cell interactions in vivo and in vitro. In suspension cultures cell adherences and contacts were interrupted by the dissociation procedure. However, contacts re-establish when cells re aggregate. In single-cell cultures, neuroblasts were cultured without cell-to cell contacts, and were deprived of potentially mediating cell interactions. Individual features of these cells supposedly reflected both the effect of the medium-derived environment and the state of their intrinsic program at the time of culturing. The neuroblasts' potential for differentiation into GABAergic neurons was studied in all three kinds of culture. GABAergic neurons developed in both tissue samples and suspension cultures, in small numbers from 11 1/2-day-old embryos (stage 19), but in increasing numbers in cortices of advanced ages. GABA immuno-reactivity starts at day 3 in vitro and persists throughout the whole culture period of up to 26 days. Neuroblasts developed in sufficient numbers without cell-to-cell contacts at the earliest in cultures from 12-day-old embryos (stage 20). At that time a few nerve cells expressed GABA after 3 days in vitro. Immunoreactivity increased and persisted until at least day 9. These results indicate that the GABAergic phenotype is expressed irrespective of whether physical cell-to-cell contacts are present or not. Moreover, differences are apparent in the intrinsic program of neuroepithelial cells prior to their display in vivo. PMID- 2244688 TI - Structure of the corpuscles of Stannius in the euryhaline teleost Takifugu niphobles (Tetraodontiformes, Teleostei), with special regard to vascularization and extravascular channel system. AB - Vascularization and the extravascular channel system of the corpuscles of Stannius in a euryhaline teleost, Takifugu niphobles, were studied by scanning electron microscopy of the vascular corrosion cast, and histochemistry of exogenously injected horseradish peroxidase as a macromolecular tracer. The corpuscles were apposed to the caudal part of the ureter, away from the mesonephric kidney, and were supplied with arterioles from the genital artery running ventrally as a ramus of the dorsal aorta. Elaborate capillary networks irrigating the glandular lobules were collected by the venules to drain into the posterior cardinal veins. Electron microscopic examination of the glands demonstrated two types of secretory cells, type-1 cells with large granules, and type-2 cells with smaller granules. The type-1 cells, predominating in the gland, occasionally showed exocytosis of the secretory granules, mainly into intercellular spaces between adjoining cells. Exocytosis was also evident in the type-2 cells. The tracer molecule injected was visualized histochemically within the capillary lumina and intercellular spaces throughout the gland. The labelled spaces intercommunicated with each other to form an extensive extravascular channel system as a diffusing pathway within the gland. The possible role of this system in hormone transport and/or storage was discussed. PMID- 2244686 TI - Anatomy of the cochlear nuclear complex of guinea pig. AB - The cyto- and fibre-architecture of the cochlear nuclear complex of the guinea pig has been studied in serial sections using Nissl, Golgi and combined cell myelin staining of normal material, and a silver degeneration method after cochlear ablation. The nuclear subdivisions and major cell types can be recognised on the basis of those found in the cat, but there are some differences between the two species in the precise distribution and morphology of the neurons. The rostrodorsal part of the anteroventral cochlear nucleus (AVCN) contains predominantly spherical bushy cells, but these cannot be readily divided into large and small types as in the cat. Globular bushy cells are seen in the caudal region of the AVCN, but the majority occur in the posteroventral cochlear nucleus (PVCN), in an area extending from the nerve root right up to the boundary of the dorsal cochlear nucleus (DCN). The octopus cells constitute a distinct region in the most dorsomedial part of the PVCN underneath the DCN. Giant cells are seen scattered around the nerve root region. Multipolar and small cells are seen throughout the non-granular regions of the ventral cochlear nucleus (VCN) except for the octopus cell area, but occur mainly in the more rostral regions of the PVCN. Small cells occur in greatest abundance in the thin cap area at the dorsal edge of the VCN below a superficial granule cell layer. The latter covers the dorsolateral surface of the VCN, and a lamina of granule cells partially separates the PVCN from the DCN. The DCN can be divided into four layers. The outermost molecular layer (layer 1) is separated from the deeper regions by a prominent layer of granule cells (layer 2) which also contains the pyramidal cells. Molecular layer stellate cells are seen in layer 1 and a staggered row of cartwheel neurons is found at the boundary between layers 1 and 2. Layer 3 contains the basal dendrites of the pyramidal cells and some small (vertical) cells, and is innervated by the descending branches of the cochlear nerve. The deepest layer 4, which contains multipolar cells and giant cells, does not appear to receive this direct cochlear input. PMID- 2244689 TI - Development of the mechanoreceptive lateral-line system in the axolotl: placode specification, guidance of migration, and the origin of neuromast polarity. AB - The mechanosensory lateral-line system offers a unique opportunity to study a wide variety of developmental phenomena, including cell migration, the origin of polarity, and pattern formation. In this study, we use a series of transplantation experiments to examine some of the factors affecting the origin of the lateral-line placodes, the establishment of sensory organ polarity and placement, and the guidance of cell migration in the Mexican axolotl (Ambystoma mexicanum). We find that placode-forming ectoderm is at least partially specified as early as the beginning of neurulation, and we suggest that this may be a result of early processes involved in neural induction. Furthermore, we find that the migration of the primordia on the body depends on the presence of both the ectoderm and the subjacent mesoderm for guidance. Sensory organ polarity on the body appears to be the result of an interaction between the primordia, which deposit organs of set polarity relative to the direction of migration, and the substrate, which determines the direction of migration. Spacing of the organs is independent of the substrate, and may be due to an intrinsic property of either the primordia or the emerging organs themselves. Finally, we suggest that the lateral-line primordia are guided, as they migrate, by a contact guidance mechanism. PMID- 2244690 TI - Regeneration of optic fibres through the chiasma in Xenopus laevis tadpoles. AB - The path through the chiasma followed by regenerating optic nerve fibres in Xenopus tadpoles was studied at light- and electron-microscopic levels, and with horseradish peroxidase as a fibre label. Over the period (5-10 days) in which regenerating fibres reach and cross the chiasma, they did not follow residual deep fibres through the chiasma, nor were they associated with the trail of degeneration in the chiasma which represented the remains of the deeper (older) parts of the original projection. The regenerating optic fibres were always seen in close association with the inner surfaces of the ependymoglial endfeet, or in the extracellular spaces that lie close to the endfeet in the most superficial part of the chiasma, where newly-growing fibres from the retinal margin are normally to be found. PMID- 2244692 TI - Cardiogenic hepatorenal syndrome. AB - A variant of hepatorenal syndrome occurring in patients with chronic congestive heart failure following an episode of cardiogenic pulmonary edema, and in the absence of hypotension, is described. This was observed in 13 patients during an eleven-year period. The clinical picture is characterized by hepatic injury and functional renal impairment. Increase of serum glutamic oxaloacetic transaminase levels as high as 2100 IU; prolongation of prothrombin time; elevation of serum bilirubin, creatinine, blood urea nitrogen, and potassium levels; decrease in urinary sodium excretion; and a normal urinary sediment are the salient laboratory abnormalities of this entity. Treated with conventional medication, the patients' course was fatal in 4 cases. When the splanchnic vasodilator dopamine was added to the patients' management, 5 of 9 patients recovered. Cardiogenic hepatorenal syndrome is a severe but potentially reversible complication of heart failure. The apparently beneficial effect of low-dose dopamine needs further evaluation. PMID- 2244691 TI - Creatine kinase isozyme expression in prenatal rat heart. AB - The distribution pattern of creatine kinase (E.C 2.7.3.2) isozymes in prenatal rat heart and skeletal muscle was studied by immunohistochemistry. Between embryonic day (ED) 12-18, creatine kinase M (CK-M) is heterogeneously expressed in the heart: a pronounced staining of CK-M is first observed in the outflow tract and the trabeculae of the right ventricle (ED12-14), and subsequently in the venous valves, the interatrial septum and the sinoatrial node. From ED18 onwards, a homogeneous expression of CK-M is observed due to an increase in isozyme concentration in the remaining part of the myocardium. By contrast, the developmental appearance of creatine kinase B (CK-B) occurs almost homogeneously throughout the heart between ED11-14. Thereafter, a decrease of the CK-B is first observed in the inflow tract (in particular in the sinoatrial node), in the inner part of those atrial walls that are adjacent to the atrioventricular junction, and temporarily in a band in the upper part of the interventricular septum. From ED18, a selective disappearance of CK-B is found in the papillary muscle of the left ventricle. At birth, a considerable amount of CK-B remains present in the ventricular walls. Although some of the stage-dependent regional differences in expression of the creatine kinase isozymes, in particular those of the M-subunit, are shared by other mammalian and avian species, their significance for the developmental changes in the physiology of the heart is speculative at present. PMID- 2244693 TI - Circumferential quantitative analysis of planar 201T1 myocardial scintigraphy in the diagnosis of coronary artery disease. AB - Methodology for the computer analysis of 201T1 myocardial perfusion images has been developed by several laboratories. Substantial evidence of the advantage of this approach over visual inspection alone has been reported. The currently available computer analyses use different algorithms to analyze 201T1 kinetics in the myocardium. The authors evaluated and compared two widely used software programs, Medical Data System (MDS): a mean-count profile, and the Cedars Sinai (CS): a maximal-count profile, of planar 201T1 scintigraphy for their ability to detect coronary artery disease (CAD). PMID- 2244694 TI - B-mode imaging and histomorphometric evaluation of carotid atherosclerosis. AB - The quantitative and qualitative evaluation of atherosclerotic lesions by the ultrasonography has presented several problems, above all, the determination of accuracy and reproducibility of this methodology in humans. The present study aims to evaluated the results of B-mode imaging of extracranial carotid arteries in patients selected for surgery as compared with histologic results of the observations of the samples obtained by endarterectomy. Shrinkage effects of the histologic samples were taken into consideration. Several bidimensional images of atherosclerotic lesions, as obtained by ultrasound at different incident angles, were used to establish their maximum thickness. The maximum degree of the vessel stenosis calculated by ultrasound showed a high correlation (Y = 0.47X + 42.4, se = 0.11, r = 0.5, p less than 0.001) compared with the one obtained by histology. The imaging methodology provided however, a mean overestimation of the stenosis of about 7%. Relationships among the amount of calcium (p less than 0.03); necrotic core p less than 0.056); and echogenic types, ie, soft, mixed, and hard; have been suggested by a statistical trend. The results suggested that of the vascular lumen due to advanced atherosclerotic lesions. Qualitative interpretation of atherosclerosis by B-mode imaging, ie, morphologic characteristics, seem, at present, to be of value, but more investigations in depth are needed. PMID- 2244695 TI - Doppler diagnostics, indications, and control of surgical treatment in patients with carotid pathology. AB - Major stroke is a relatively common cause of death or disabling invalidism in patients with atherosclerosis. In a large percentage of cases it is caused by stenotic/thrombotic processes in carotid arteries and this emphasizes the importance of the problem of early diagnosis and treatment of carotid pathology. Recently Doppler sonography has become a leading non-invasive method of early screening of stenotic processes in carotid arteries. The aim of the present study was to ascertain the diagnostic abilities of Doppler sonography for screening of carotid pathology, assessment of extra-cranial and intracranial hemodynamics, defining of indications, and control of vascular reconstructions of carotids. PMID- 2244696 TI - Significance of U wave polarity in patients with a prior inferior myocardial infarction. AB - Sixty consecutive patients who underwent coronary angiography and left ventriculography from six to eight weeks after the onset of definite inferior myocardial infarction were divided into three groups according to the polarity of U waves in (1) leads II, III, a VF and (2) in leads V4 to V6 (positive = Group P, flat or isoelectric = Group F, and negative = Group N). The following parameters were analyzed: (1) ECG score; (2) global ejection fraction: (3) regional area change: (4) number of asynergic, and akinetic segmental radii; (5) number of asynergic and akinetic areas: and (6) number of diseased coronary arteries and the incidence of left anterior descending artery (LAD) disease. There were no significant differences among the three groups according to the polarity of U waves in two subgroups by the site of U waves in age, gender, systemic blood pressure, and ECG scores. The polarity of U waves in leads II.III.a VF (subgroup 1) correlated with the size of myocardial infarction; regional area changes in inferior segment (Area 2) were 64.1 +/- 8.2 in group P1, 31.8 +/- 14.7 in group F1, and 21.0 +/- 15.8 in group N1 (p less than 0.01, F = 32.8). The polarity of U waves in leads V4-6 (subgroup2) correlated with anterolateral wall motion; regional area changes in anterolateral segments (Area 5) were 76.8 +/- 11.6 in group P, 66.5 +/- 18.5 in group F, and 48.9 +/- 17.1 in group N (p less than 0.01, F = 18.6). The incidence of multivessel disease increased from group P2 (36.4%), to group F2 (54.5%), to group N2 (75.0%), and the incidence of LAD disease increased from 27.3%, to 45.5%, to 68.8%, respectively. A negative U wave in either location suggested severely decreased apical wall motion, and there was a tendency for global ejection fractions to decrease in the following order: group P, group F, and group N. From these results, the authors conclude that the polarity of U waves may be one of the parameters correlating with the wall motion and left ventricular function in prior inferior myocardial infarction. PMID- 2244697 TI - Conduction system injury after aortic valve dilation in the dog single- versus double-balloon catheters. AB - The range of morbidity induced by valvuloplasty is not fully known, but transient conduction disturbances are common. The authors performed aortic valve balloon dilatation on 10 closed-chest dogs with normal aortic valves, using a femoral cutdown approach and fluoroscopic guidance. Four were done with a single 15 mm balloon catheter, and in the other 6 two 12 mm balloon catheters were used. Balloons were inflated to 5 to 12 atms pressure with contrast solution. After several inflations the dogs were sacrificed, the hearts removed and examined. Gross examinations revealed subendocardial hemorrhage in the outflow tract in 5 of the 6 in which double balloons had been used. Microscopically, all aortic valve areas showed hemorrhage, mostly in loose connective tissues of the valve leaflets. The severity of injury appeared greater when two balloons had been used. Histologic examination showed definite injury to the myocytes of the left bundle branch in all 6 of the double-ballooned dogs, but in none of those subjected to the single-balloon procedure. During aortic valve dilation the only manifestation of conduction system injury was prolongation of the QRS complex in 3 of the 6 dogs in which a double-balloon catheter had been used. The results suggest that electrocardiographic conduction disturbances observed in patients undergoing aortic valvuloplasty may be the result of direct injury of conduction tissue and may be more likely to occur when larger balloons are used. PMID- 2244698 TI - Patency rate of implantable devices during long-term intraarterial chemotherapy. AB - Intraarterial implantable drug delivery systems have been considered as an alternative method for treating patients with unresectable liver malignancies. However, catheter problems with external implanted devices have resulted in limited application of chemotherapy. The introduction of subcutaneous devices offers an opportunity for long-term locoregional chemotherapy. Twelve external intraarterial catheters were implanted into 12 patients and 52 subcutaneously placed devices into 51 patients, all with various hepatic malignancies. Retrospective analyses comparing those two intraarterial systems were conducted taking into account the function and complication rate (hepatic artery thrombosis, infection, leaking, hemorrhage, and dislocation). The follow-up time for the external system was two to eight months (median five weeks), the thrombosis rate 33.3%, and the infection rate 25%. One instance of severe bleeding from the hepatic artery occurred during chemotherapy. One catheter dislocated. For the subcutaneously implanted intraarterial devices the follow-up time was five to forty-one months (median sixteen months), the thrombotic complication rate 17.3%, and the infection rate 7.6% (all patients with simultaneous bowel surgery). Catheter dislocation one year later required reimplantation; in 1 patient therapy had to be discontinued because of a catheter leak. The overall function rate was 71.3% with a median follow-up time of eight months. Anticoagulation therapy for subcutaneously implanted devices starting from the beginning of intraarterial chemotherapy is recommended to achieve long term patency. No implantation should be preformed simultaneously with bowel surgery. The subcutaneously placed intraarterial devices had a higher function rate and were available for a longer period as compared with external implanted catheters. PMID- 2244699 TI - A pitfall in azygos vein cannulation in cirrhotic patients: mistaken cannulation of the mammary vein. AB - Azygos venous flow can be measured by a thermodilution catheter in patients with cirrhosis. This is a useful technique since azygos flow is thought to reflect the superior portosystemic collateral flow in these patients. The authors report 3 cases in which mistaken internal mammary vein cannulation mimicked azygos vein cannulation in the supine fluoroscopic view. A lateral fluoroscopic view confirmed internal mammary cannulation. They suggest that if the azygos arch is unpronounced or flow measurements are unexpectedly low in patients with portal hypertension due to cirrhosis, a lateral view be performed to rule out internal mammary vein cannulation. PMID- 2244700 TI - Lymphangiomyomatosis--newer concepts in pathogenesis and management--case reports. AB - Lymphangiomyomatosis was first reported more than forty years ago. Although its incidence is rare, its occurrence is being increasingly recognized and has been the subject of a growing number of cases reports in recent years. This study adds 2 more cases to the file. Both cases involved young women with the characteristic symptoms of dyspnea, cough, abdominal discomfort and swelling, chest pain, and hemoptysis, with abundant formation of refractory chylous, serous ascites. Although the progression of the disease differed in each case, pulmonary function was affected in a similar way by the presence of obstructive and restrictive defects and a decrease in diffusing capacity. Underlying abnormalities were dilated lymphatics, thickened lymphatic walls, and muscular proliferation of leiomyomatous origin, leading to bronchial restriction. The authors point to the subtlety required in arriving at a differentiated diagnosis of lymphangiomyomatosis lymphangioleiomyomatosis and the difference between the two conditions. They also make particular recommendations in respect to the importance of preliminary hormone receptor tests and to the wisdom to be exercised in ligating a main lymphatic duct in the chest to control the formation of ascites. Pneumothorax, a frequent manifestation of lymphangiomyomatosis, is found to be the result of chronic air trapping due to a combination of narrowing of conducting airways and disruption of normal lung parenchyma. PMID- 2244701 TI - Steroid anabolic drugs and arterial complications in an athlete--a case history. AB - Serious side effects and complications have been attributed to anabolic and androgenic steroids when used for medical reasons or when taken in sports in hopes of increasing strength and, hence, performance. The author presents a case of an athlete who experienced two metachronous arterial complications after taking these drugs: a cerebrovascular accident caused by a carotid artery thrombus that partially embolized to the brain and, later, a severe ischemic episode in a lower limb caused by a diffused distal arterial thrombosis. This patient represents the first reported case of vascular events in an otherwise healthy athlete taking androgens to increase his skeletal muscle mass. PMID- 2244702 TI - Platelet aggregation is not necessary for occurrence of Raynaud's phenomenon: a clinical history and laboratory results. AB - "Raynaud's phenomenon (R.P.) is characterized by a spastic vasoconstriction of hand and/or feet extremities leading to painful ischemic attacks. In the pathogeny of this syndrome the role of a platelet hyperactivation was evidenced. Nevertheless, the responsibility of platelet aggregation remains controversial. We report here the case of a patient presenting with a Glanzmann thrombasthenia defined by the complete lack of platelet aggregation, and showing a typical RP which was confirmed by the measurement of hand temperature and the decrease of digital and hand blood flow. Thus, the description of this case shows that platelet aggregation by itself is not necessary for the occurrence of RP, and encourages for therapeutic purposes the development of vasodilatators rather than platelet antiaggregants agents." PMID- 2244703 TI - Large arteries involvement in scleroderma--a case report. AB - The authors describe a thirty-nine-year-old woman patient presenting with progressive systemic sclerosis and an unusual angiographic picture of an impairment of large arteries, which in their opinion is due to the primary disease. The review literature reports about similar arterial involvement in scleroderma. PMID- 2244704 TI - Effects of air pollution on asthma. PMID- 2244705 TI - Masqueraders in clinical allergy: laryngeal dysfunction causing dyspnea. AB - The allergist may be called upon to evaluate patients with dyspnea that is labeled "refractory asthma." In some patients, the site of origin of their dyspnea is the larynx. The diagnosis of laryngeal disorders requires a thorough understanding of the normal function of the laryngeal anatomy and physiology. Some patients with asthma may have a component of their airway obstruction in the larynx and large airways. Paradoxical vocal cord motion occurs when the true vocal cords approximate during inspiration, and although severe subjective dyspnea may occur, in most cases there is no evidence of hypoxia, hemoglobin desaturation, or an abnormality of the arterial-alveolar oxygen gradient. Provocative tests with methacholine are negative in this group of patients. Patients with PVCM are usually female and may have an affiliation with the medical profession. Many have psychologic difficulties, and the foundation of treatment is speech therapy and psychotherapy if indicated. Other disorders that may produce dyspnea from laryngeal dysfunction include Meige syndrome, abductor spastic dysphonia, and laryngospasm. Recognition of these disorders will expedite timely, accurate diagnosis and treatment. PMID- 2244706 TI - Hypogammaglobulinemia. PMID- 2244707 TI - Mast cell heterogeneity in chronic idiopathic urticaria. AB - Patients with chronic urticaria are more sensitive to codeine skin testing than other allergic individuals. Nonlesional skin in most patients with chronic urticaria was found to contain increased numbers of both total and atypical mast cells. The presence of increased mast cell density was found to correlate with the degree of clinical (dermatographism) and functional (codeine skin test) skin sensitivity. PMID- 2244708 TI - Silk-induced asthma in children: a report of 64 cases. AB - A total of 64 children less than 15 years of age with asthma caused by silk were studied. The diagnosis was based on a history of wheezing, positive skin tests to silk, positive conjunctival or nasal provocation tests, or serum IgE-Sw (silk waste). The average age of onset was 4 years 2 months. Sex ratio (M:F) was 3.6:1. A positive skin test is essential for the diagnosis. Conjunctival provocation tests were performed in 80% of cases because of reliability, safety, and convenience. The first symptom appeared an average of 10 months after initial exposure to silk. In 61% of patients, asthma was accompanied by allergic rhinitis but in only 14% of cases by conjunctivitis. In most cases, asthma occurred in winter, due to seasonal use of bed quilts or clothes filled with silk. Silk is a highly potent allergen. The average mean wheal diameter elicited by silk in prick testing was larger than two histamine equivalent prick tests. A cross reactivity exists among mulberry silk, and silkworm cocoons, batryticated silkworms, and silkworm chrysalis. PMID- 2244709 TI - Low level atmospheric sulfur dioxide pollution and childhood asthma. AB - Quarterly analysis (1983-1987) of childhood asthma in Hong Kong from 13,620 hospitalization episodes in relation to levels of pollutants (SO2, NO2, NO, O3, TSP, and RSP) revealed a seasonal pattern of attack rates that correlates inversely with exposure to sulfur dioxide (r = -.52, P less than .05). The same cannot be found with other pollutants. Many factors may contribute to the seasonal variation of asthma attacks. We speculate that prolonged exposure (in terms of months) to low level SO2 is one factor that might induce airway inflammation and bronchial hyperreactivity and predispose to episodes of asthma. PMID- 2244710 TI - A random double-blind trial of the combination of nebulized atropine methylnitrate and albuterol in nocturnal asthma. AB - The combination of nebulized atropine methylnitrate (AMN) and a beta-agonist has been shown to produce greater and longer lasting bronchodilation than either drug alone. We examined the efficacy of the combination in diminishing the "morning dipping" in PEFR in eight hospitalized but stable asthmatics. The patients received nebulized albuterol along with either AMN (AMN + ALB) or placebo (ALB) in a random double-blind cross-over fashion at 10 PM on four nights. PEFR and FEV1 were recorded at 6 PM, 10 PM, and 6 AM before the administration of bronchodilators. There was no statistically significant difference between ALB and AMN + ALB in reducing the morning dipping in these patients. PMID- 2244711 TI - Pollen and mold allergy: aerobiologic survey in the atmosphere of Cagliari, Italy (1986-1988). AB - The occurrence of pollens and molds in the atmosphere of Cagliari, Italy over a 3 year period (1986-88) is reported. Pollen grains are present in the air from February to July, with a maximum in May. Urticaceae and Cupressaceae were the major contributors to the total pollen airspora, followed by Graminaceae, Oleaceae, Pinaceae, Cheno-Amaranthaceae, and Fagaceae. Fungal spores showed two periods of high sporulation, from April to June and in September-October, and two marked decreases, during winter and August. Cladosporium was by far the most abundant spore identified, followed by Basidiomycetes, Alternaria, and Fusarium. PMID- 2244712 TI - Evaluation of ketotifen in corticosteroid-dependent idiopathic anaphylaxis. AB - To study the possible efficacy of ketotifen (K) in the treatment of idiopathic anaphylaxis (IA), K was administered in an open-label trial to six patients with IA who required corticosteroids at doses below which their disease could not be controlled. During the study, patients continued to receive noncorticosteroid medications (eg, antihistamines, oral adrenergic agents) that had been used on a regular basis for treatment of IA before study, but periodic attempts to reduce corticosteroid doses were made. A reduction of prednisone dose with continued control of disease was judged to be evidence for a beneficial effect of K. After 7 to 16 months of K administration, three patients were judged to have had probable benefits from K (reductions in alternate day prednisone dose requirement from 40 mg to none, 35 mg to 15 mg, and 30 mg to none), and one patient had a possible benefit from K (dose reduction from 100 to 120 mg to 77 mg). Two other patients were unable to tolerate major decreases in prednisone without developing symptoms or signs of IA. Within the limitations of this study design, we conclude that K may be efficacious in the treatment of some patients with IA, and that further trials of K in the treatment of IA are indicated. PMID- 2244713 TI - Type I hypersensitivity to rubber. AB - Seven patients with type I hypersensitivity reactions to rubber are reported. Radioallergosorbent testing with crude latex antigen was positive in 6/7 patients. Five patients had coexisting spina bifida, and all had undergone surgery before the development of rubber allergy. Rubber allergy is a new phenomenon that should be in the differential diagnosis of idiopathic anaphylaxis and urticaria. PMID- 2244715 TI - Diagnosis of mold allergy by RAST and skin prick testing. AB - Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum. PMID- 2244714 TI - Anaphylaxis to grand keyhole limpet (abalone-like shellfish) and abalone. AB - We report five patients who developed moderate to severe anaphylactic reactions induced by the ingestion of grand keyhole limpet (GKL) and abalone. Specific IgE mediated hypersensitivity to these shellfish was demonstrated by history, prick skin test, and RAST. RAST inhibition technique revealed the cross-antigenicity between GKL, abalone, and keyhole limpet hemocyanin. PMID- 2244716 TI - Outpatient management of traumatic microhyphemas. AB - Traumatic microhyphema is an entity encountered in emergency rooms and general ophthalmology practices. The management of traumatic microhyphema has not been well defined in the literature. We discuss the effectiveness of our treatment regimen and the incidence of rebleed in patients with microhyphema. PMID- 2244717 TI - Ocular atopy and mycotic keratitis. AB - In a retrospective analysis, we studied the association between ocular atopy and keratomycosis. Forty-one (26.3%) of 156 patients with fungal corneal ulcers were found to have preexisting allergic conjunctivitis. All patients had been using a combination of antibiotics and corticosteroids before developing the corneal ulcer. Fungus isolation on Sabouraud's agar medium was obtained in 74.8% (31/42) ulcers. The most common fungi isolated were Fusarium (32.3%) and Aspergillus (29%). One percent silver sulfadiazine was used as an antifungal agent in these patients. Overall efficacy of this drug was found to be 77.8%, with Fusarium being the most sensitive (87.5%). PMID- 2244718 TI - Intraocular foreign bodies: results of 27 cases. AB - Twenty-seven consecutive cases of various kinds of perforating injuries with foreign bodies, referred to the Ophthalmology Department of Hacettepe Medical School between January 1984 and April 1988, were evaluated retrospectively. Whenever technically possible magnetic extraction was the preferred method of removing the foreign body. Thirteen (48%) eyes developed endophthalmitis, 18 (66.6%) eyes developed traumatic cataract, and eight (29.6%) eyes developed retinal detachment after the trauma. Twelve (44.5%) eyes had a visual acuity of 1/10 or better after the appropriate medical and surgical treatment. PMID- 2244719 TI - Intraocular lens complications. AB - The authors implanted intraocular lenses (IOL) in 780 eyes and considered complications of this surgery, dividing the complications into intraoperative and postoperative, the latter early and late. The most frequent intraoperative complications were: hyphema, vitreous injury, pupil deformation with an IOL in the anterior chamber (AC), and hyphema and corneal lesions with an IOL in the posterior chamber (PC). Among the early postoperative complications of an IOL in the AC the authors noticed striate keratopathy and uveal flare and postoperative transitory ocular hypertension and striate keratitis with an IOL in the PC. Moreover, in late postoperative complications in AC implantation they observed: cystoid macular edema, bullous keratitis, retinal detachment, late uveitis, opacification of posterior capsule, eccentric displacement of the IOL, and less frequently, cystoid macular edema in PC implantations. The authors prefer IOL implantation in the PC after extracapsular cataract extraction, since this surgery causes less problems in the cornea, vitreous, and retina. PMID- 2244720 TI - The 30-degree curved endolaser probe. AB - Straight, 30-, and 45-degree endolaser probes were compared to determine the optimal curve for peripheral endolaser photocoagulation during pars plana vitrectomy. The 30-degree probes allowed panretinal laser coverage in phakic eyes, thereby negating the need for peripheral cryopexy which may cause increased inflammation and contribute to the development of proliferative vitreoretinopathy. The 30-degree probe was less likely to strike the lens inadvertently, produced a more consistent burn, was more versatile in posterior treatments, and had a longer fiberoptic core life than the 45-degree probe. It was impossible to treat the peripheral retina using the straight probe without hitting the lens during phakic pars plana vitrectomy. PMID- 2244721 TI - Endophthalmitis due to Sporothrix schenckii after penetrating ocular injury. AB - A 13-year-old boy developed endophthalmitis from traumatic inoculation of vegetable material penetrating his right eye. Sporothrix schenckii was morphologically identified from the intraocular fluids. However, repeated attempts to culture the organism proved negative. Seventeen sporotrical endophthalmitis cases have so far been reported, and before this report, only one of them was secondary to trauma. This is the sole eye to our knowledge not only to have escaped enucleation after sporotrical endophthalmitis but to have achieved useful (20/50) vision. PMID- 2244722 TI - Ultrasonic forms of posterior staphyloma. AB - The most frequent deformations of the globe encountered in pediatric ophthalmology are staphylomas and colobomas. In this paper we reviewed 16 ultrasonographically diagnosed staphylomas and classified the ultrasonographic patterns produced by staphyloma cases into four types: (1) staphylomas involving the posterior pole but not the optic nerve head, (2) staphylomas involving the posterior pole and the optic nerve head, (3) peripapillary staphylomas, and (4) giant peripapillary staphylomas. Morphologic and ultrasonographic characteristics are described. PMID- 2244723 TI - Effect of local anesthesia and ocular massage on central corneal curvature. AB - Using a standard Javal keratometer, we obtained central corneal curvature measurements in 19 patients before and after the administration of local anesthesia. We noted flattening of mean average keratometry which approached statistical significance, along with an increase in overall astigmatism. Decreased intraocular pressure was not found to be a factor. PMID- 2244724 TI - Spontaneous pneumopericardium and pneumomediastinum. PMID- 2244725 TI - Removal of blunt foreign bodies from the esophagus. AB - Historically, removal of blunt foreign bodies from the esophagus by esophagoscopy under general anesthesia has been considered to be relatively safe and effective. In recent years, alternative techniques of blind removal with balloon catheters or bougies have been advocated. This paper reports 246 esophagoscopies performed over a 19-year period to remove blunt esophageal foreign bodies. Eighty-one percent of the foreign bodies were coins and 74% were in children under 3 years of age. There were no deaths, no perforations, and no instances of mediastinitis. The only complications encountered were those due to esophageal erosion and/or respiratory problems secondary to long-standing foreign bodies. In the author's opinion, esophagoscopy is the best method for removal of all esophageal foreign bodies. There simply does not seem to be a need for alternative methods involving blind removal. PMID- 2244727 TI - Endoscopic management of early supraglottic cancer. AB - An initial endoscopic surgical approach to early supraglottic cancer provides the surgeon with the ability to accurately stage these lesions, avoiding possible undertreatment while allowing for a valuable treatment option for those supraglottic cancers with histologically incontrovertibly superficial disease. Early invasion of the preepiglottic and paraglottic spaces can be determined accurately without altering or delaying any treatment option (open surgical excision, radiotherapy, or chemotherapy). The tendency of supraglottic cancers to transgress the natural foramina of the epiglottis is well established, and the concern about this depth of invasion is reflected by the 1977 revised staging criteria, which required assessment of the preepiglottic space (PES). Along with the microscope and the carbon dioxide laser, the adjustable supraglottiscope facilitates the determination of PES invasion and facilitates en bloc excision of superficial supraglottic cancers. The resulting morbidity typically is no different from that with routine direct endoscopy and biopsy. PMID- 2244726 TI - Platysma myocutaneous flap for repair of hypopharyngeal strictures. AB - Hypopharyngeal strictures, either isolated or in conjunction with laryngeal and esophageal strictures, can occur following lye ingestion. Extensive stricture formation requires reconstruction to create a functional funnel system that empties below the cricoid. Esophageal replacement is not a substitute for adequate hypopharyngeal reconstruction. The pectoralis major muscle is often inadequate, because it yields too much bulk and often leads to continued aspiration. The platysma myocutaneous flap for hypopharyngeal reconstruction has not been previously reported. The inferiorly based platysma myocutaneous flap was used in two of our patients with lye burns, and bilateral superiorly based flaps were used in one. All are able to eat normally and have no significant stenosis. The platysma myocutaneous flap is a relatively simple and reliable alternative that is within the capability of every head and neck surgeon. PMID- 2244728 TI - Bilateral semicircular canal aplasia with near-normal cochlear development. Two case reports. AB - Congenital malformations of the vestibular labyrinth (pars superior) are rare. We present two patients with computed tomographic findings of bilateral semicircular canal aplasia with normal or near-normal cochleas. Initial bone conduction thresholds were within normal limits, although both patients had significant conductive hearing losses due to congenital middle ear malformations. Bithermal caloric responses were absent in both. To our knowledge these are the first reports of vestibular aplasia concomitant with normal or near-normal cochlear development. These findings conflict with conventional hypotheses that state that inner ear malformations result from arrested development during the normal stages of inner ear embryogenesis. PMID- 2244729 TI - Idiopathic sudden sensorineural hearing loss and postnatal viral labyrinthitis: a statistical comparison of temporal bone findings. AB - Although the cause of idiopathic sudden sensorineural hearing loss remains uncertain, a viral origin has been suggested in many cases on the basis of anamnestic microbiologic and pathologic data. Twenty-two temporal bone specimens from 18 patients who during life suffered a sudden partial or complete sensorineural hearing loss were studied. On the basis of clinical data, these cases were assigned to one of three diagnostic categories, and the temporal bones were studied by light microscopy and serial section analysis. The implications of the histopathologic findings for the pathogenesis of idiopathic sudden sensorineural hearing loss are discussed. PMID- 2244730 TI - Conversion between systems of hearing handicap measurement: an empirically determined computational procedure. AB - Audiograms collected from 821 individuals were used to determine the interrelationships among five systems of determining hearing handicap based upon pure-tone thresholds. These were the American Academy of Ophthalmology and Otolaryngology, the British Association of Otolaryngologists and the British Society of Audiology, the American Medical Association, the industrial, and the full-range averages. A high degree of correlation (average r = .981) was found among the various indices. Using the regressions between all possible pairs of indices, we constructed a table that allows conversion between the various systems involving only very simple computation. PMID- 2244731 TI - Microbiology of "normal" tonsils. AB - Core tonsillar cultures for aerobic and anaerobic bacteria were performed on four normal tonsils removed from four children because of velopharyngeal insufficiency and on four tonsils removed from four children because of recurrent tonsillitis. The data illustrate the presence of polymicrobial flora in the cores of normal noninflamed tonsils and the increase in their number and encapsulation during the inflammatory process. PMID- 2244732 TI - Age-related changes in evoked otoacoustic emissions. AB - Outer hair cells of the organ of Corti play an important part in the genesis of evoked otoacoustic emissions (EOAEs), which are related to cochlear biomechanics. The aim of this study was to investigate the age factor in relation to EOAEs in 166 ears of subjects between 6 weeks and 83 years of age. The results show that when age increases, the presence of EOAEs by age group and the frequency peak in spectral analysis decrease, and EOAE threshold increases. Thus, there is an effect of age upon EOAEs, and it seems linked with alteration of cochlear biomechanics and/or hair cell loss. Such an effect has to be taken into consideration when EOAEs are used in clinical applications, and limits the use of EOAEs in older subjects. PMID- 2244733 TI - Let us proceed with due deliberation. PMID- 2244735 TI - Extending the reach of island cutaneous flaps. AB - The advancement of island cutaneous flaps beyond 2 cm is facilitated by an understanding of underlying vascular anatomy. Recent studies demonstrate the perforating cutaneous blood vessels of the body. When extensive mobility is required, an island cutaneous flap should be centered over these vessels. The perforating cutaneous vessels and, if necessary, the axial vessels are identified, which permits vigorous dissection of restraining fascia and muscle. Clinical experience during the past 14 years suggests that the medial face is an ideal location for island cutaneous flaps. Flap design in the trunk and extremities incorporates known septal and subcutaneous fascial perforators. Fourteen of 53 island cutaneous flaps were advanced distances greater than 2 cm without significant complications. PMID- 2244734 TI - Lateral approach in mammary implants. AB - The lateral approach in mammary implants is recommended, especially in patients with a marked hypomastia. In these patients, submuscular implants are mandatory. Routinely, hyaluronidase is injected in situ before implantation to favor immediate reabsorption of possible bleeding that could lead to capsular contraction. A circular pattern has been designed to reach symmetry both in incisions and the surgical pocket. Advantages of the lateral approach are described. PMID- 2244736 TI - Refinements of nasalis myocutaneous flap. AB - During the last 3 years, we have applied the nasalis myocutaneous island flap for reconstruction of nasal defects following excision of skin basal cell carcinoma and melanoma in 19 patients. By refinements with Z plasty, early dermabrasion, and placement of a bolster, we could minimize the trapdoor deformity, obvious scars, and blunting of the alar groove. No patients required revisional surgery, and flap survival was 100%. On the basis of our experience, the nasalis myocutaneous island flap is the solution for reconstruction of moderate-sized distal nasal defects in terms of reliability, aesthetics, and simplicity. PMID- 2244737 TI - The role of intraarterial vasodilators in the treatment of inadvertent intraarterial injection injuries. AB - Inadvertent arterial injections, both in cases of drug addiction and in iatrogenic situations, often result in significant loss of tissue and, eventually, loss of function distal to the injection site. Previous experimental studies regarding the effectiveness of agents to reverse vasospasm have been inconclusive. A recent clinical report, however, suggested that intraarterial injection of reserpine was affective in limiting tissue necrosis. This experiment was designed to study the affect of intraarterially injected reserpine and tolazoline hydrochloride in a rabbit ear model of necrosis following intraarterial injection of pentothal. Six groups of 5 rabbits each were studied. Animals in Group 1 received intraarterial saline injections. Animals in Group 2 received intraarterial pentothal. Animals in Group 3 received intraarterially injected pentothal plus intraarterial reserpine 30 minutes later. Animals in Group 4 received intraarterially injected pentothal plus intraarterial tolazoline 30 minutes later. Animals in Group 5 received intraarterially injected pentothal plus intraarterially injected reserpine and intraarterially injected tolazoline both administered immediately. Animals in Group 6 received intraarterially injected pentothal plus intraarterially injected reserpine and intraarterially injected tolazoline, both administered 30 minutes later. Results showed no significant difference in the amount of tissue necrosis between treated and untreated animals. We conclude that the use of intraarterial spasmolytic agents has no effect on the course of tissue necrosis after inadvertent intraarterial injections. PMID- 2244738 TI - Osteocutaneous flap from the big toe for repair of osteomyelitis of the second toe. AB - The free vascularized osteocutaneous flap from the big toe has been offered as a solution for the reconstruction of the distal phalanx of the fingers. As another important application of this flap, it is recommended that the flap pedicled with the plantar vessels can easily cover the defect involving the bone of the second toe. PMID- 2244739 TI - Full-thickness cheek and lip reconstruction with the radial forearm free flap. AB - The radial forearm free flap has proven versatility in head and neck reconstruction. It is superior to regional alternatives such as the pectoralis flap because it is thin, pliable, and predominantly hairless. A more recent application is the use of the folded forearm flap to replace both the skin and inner lining, simultaneously, in full-thickness cheek and lip defects. Nine such cases are presented in this report. Each patient had a recurrent lesion that had been reconstructed previously with local flaps, and all but one were treated with postoperative radiation therapy. The average size of the external defects after resection was 27 cm2, and of the intraoral defects, 18 cm2. All free flaps survived completely. The folded forearm flap solved the reconstructive problem for each patient in a single-stage procedure, providing good contour and a reasonable color match. The flap is easy to raise, has a long pedicle with large diameter vessels, and has an acceptable donor site defect not associated with long-term morbidity. PMID- 2244740 TI - Dermatofibrosarcoma protuberans of the toe. AB - Dermatofibrosarcoma protuberans is an unusual soft-tissue tumor with a propensity for local recurrence and occasional metastatic spread. Given its indolent course, it may be mistaken for atypical scarring or a keloid growth. Most lesions are trunkal or on the proximal extremities with digital lesions being extremely rare. There is only one previous reference of the tumor arising on a toe. Early diagnosis and prompt wide local resection of this entity are required to prevent a local recurrence, which would necessitate a wider, more debilitating resection. The management of a patient with a dermatofibrosarcoma protuberans of the second toe is presented along with a review of the literature. PMID- 2244741 TI - W-plastic rotation flap to cover nasal defect. AB - Keeping in mind the direction of the relaxed skin tension lines (RSTL), we used a local W-plastic rotation skin flap from the cheek to cover a large nasal defect resulting from the excision of a benign skin lesion. This technique, first described by Imre [7], is superior to the direct single-pedicle advancement flap from the cheek, or to any nasolabial flap, for repair of such nasal defects. PMID- 2244742 TI - Reverse-flow posterior tibial island flap: preliminary report of a new fasciocutaneous flap. AB - Septocutaneous vessels constitute an important source of skin circulation in the leg and form the basis of various fasciocutaneous flaps that have useful clinical applications. In 1978, Goufan and Baogui described a flap from the forearm based on the radial artery (Chinese forearm flap). With this in mind, the reverse-flow posterior tibial fasciocutaneous flap (Thai leg flap, or TLF) was designed and successfully transferred clinically to cover lower leg and foot defects in 2 patients. The factors that permit a distally based flap to be raised in the lower leg against the direction of the venous valves, and the backflow of arterial blood, are also described. The versatility, advantages, and disadvantages of this new flap in the reconstruction of defects of the lower leg and foot are discussed. PMID- 2244743 TI - Secondary reconstruction by temporoparietal free fascial flap for ring avulsion injury. AB - We report the secondary reconstruction of an amputated finger following a ring avulsion injury using a temporoparietal fascial flap (TPFF). There have been reports of preserving degloved fingers using a cross-finger flap and an abdominal flap, but it is difficult to obtain good results with these procedures. The TPFF is an ideal, thin flap that gives excellent results, preserving movement of the phalangeal joint. PMID- 2244744 TI - Irradiated homologous costal cartilage for augmentation rhinoplasty. AB - Although the ideal reconstructive material for augmentation rhinoplasty continues to challenge plastic surgeons, there exists no report in the literature that confines the use of irradiated homologous costal cartilage, first reported by Dingman and Grabb in 1961, to dorsal nasal augmentation. The purpose of this paper is to present a retrospective analysis of the author's experience using irradiated homologous costal cartilage in augmentation rhinoplasty. Twenty-seven dorsal nasal augmentations were performed in 24 patients between 16 and 49 years of age with a follow-up ranging from 1 to 27 months. Good-to-excellent results were achieved in 83.3% (20 of 24). Poor results requiring revision were found in 16.7% (4 of 24). Complication rates included 7.4% infection (2 of 27) and 14.8% warping (4 of 27). The resorption rate was zero. These results compare favorably with other forms of nasal augmentation. Advantages and disadvantages of irradiated homologous costal cartilage are discussed. PMID- 2244745 TI - Re: Parotid salivary fistula following rhytidectomy. PMID- 2244746 TI - Intersalt in Newfoundland and Labrador. AB - In Intersalt, positive relations between 24-hour urinary sodium and potassium excretion and blood pressure were observed in over 10,000 men and women in 52 centers around the world. Body mass index (BMI), alcohol intake and smoking showed different associations with blood pressure in various population groups. We investigated these variables in the 2 Canadian centers and could not confirm the sodium-potassium relationship. In a multiple stepwise regression analysis, BMI and alcohol had the strongest relation with blood pressure in men. Among the female participants, BMI and sodium were the most influential factors on systolic blood pressure. For diastolic blood pressure, BMI and smoking showed the strongest significance. Neither in men nor in women could the influence of high sodium and low potassium excretion on blood pressure be discerned. PMID- 2244747 TI - Effects of anoxia and low free fatty acid on myocardial energy metabolism in streptozotocin-diabetic rats. AB - To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization. PMID- 2244748 TI - Incidence of biochemical vitamin B6 deficiency in Nigerian adolescents. AB - The vitamin B6 status of 120 apparently healthy adolescents (83 males and 37 females) was assessed from dietary vitamin B6 intake, the measurement of erythrocyte alanine amino transferase activity (E-ALAT) and its in vitro stimulation by pyridoxal phosphate (PLP). The mean daily vitamin B6 and protein intakes of the adolescents were 1.52 +/- 0.4 mg and 62.04 +/- 8.3 g, respectively. Male adolescents had slightly higher (p less than 0.05) basic and stimulated E-ALAT activities than female adolescents. Dietary vitamin B6, protein intake, age and menarche also had no significant effect (p greater than 0.05) on E-ALAT measurements. Adopting an E-ALAT in vitro percentage stimulation of less than 16% as a criterion for vitamin B6 adequacy, 34% of these adolescents had poor vitamin B6 status. The similarity in the incidence of vitamin B6 deficiency among the male (33%) and female (36%) adolescents suggests that both sexes may equally be at risk to biochemical vitamin B6 deficiency. Supplementation of regular diets of institutionalised adolescents with pyridoxine or a combination of other water-soluble vitamins is suggested. PMID- 2244749 TI - Effect of decreased food consumption during iron deficiency upon growth rate and iron status indicators in the rat. AB - Weanling Wistar rats were given a low-iron diet (4-5 mg Fe/kg), a medium-iron diet (20 mg Fe/kg) or a control diet (40 mg Fe/kg) for 7 weeks. Pair-fed rats received the control diet in amounts equivalent to that consumed by animals on a low-Fe diet. Blood samples from the tail vein were taken after 4 weeks of diet and weekly during the following 3 weeks for determination of iron status parameters. Animals were weighed weekly. After 4 weeks of diet, the rats fed the 5 mg iron/kg diet were severely anemic and rats fed 20 mg iron/kg diet were moderately iron-deficient. Ad libitum and pair-fed controls had normal iron status. Total liver iron stores were lowest in anemic rats (p less than 0.001) and were also low in moderately iron-deficient animals (p less than 0.05). Growth rates decreased early in anemic and pair-fed rats. Both groups were smaller than controls and moderately iron-deficient rats after 2 weeks (p less than 0.05) and this continued until the end of the experiment (p less than 0.001). Body weights of pair-fed rats were lower than those of anemic rats from the 1st to the 3rd week of diet; thereafter, differences between the two groups were no longer significant. PMID- 2244750 TI - Effect of methylxanthines on lactational performance of rats. AB - Caffeine, theophylline and theobromine are commonly consumed methylxanthines. There are conflicting reports that methylxanthines may adversely affect the outcome of pregnancy. The effects of methylxanthines on lactational performance were investigated by administration of pure alkaloids via drinking water to Wistar albino rats throughout pregnancy and lactation. Litter growth was used as an index of lactational performance in relation to maternal food and fluid intake, changes in weight, and lipid content of the carcass. Caffeine induced increased fluid intake (p less than 0.01). While theophylline produced no significant differences in litter growth, maternal weight and carcass fat during pregnancy/lactation compared with controls, caffeine and theobromine significantly enhanced litter growth (p less than 0.05 and 0.01, respectively). The enhancement in pup growth did not involve increases in maternal food intake or maternal lipid mobilization. PMID- 2244751 TI - Steroid pattern of bile and feces in response to a fruit-enriched diet in hypercholesterolemic hamsters. AB - The effect of a fruit (apple)-enriched diet on bile secretion and on fecal steroid excretion was studied in two strains of hamster: normal hamsters with normal cholesterolemia and spontaneous hypercholesterolemic hamsters with high level hepatic cholesterol esters (FEC hamsters). Quantitative and qualitative alterations in the steroid composition in bile and feces were accompanied by changes in intestinal morphology. The fruit diet displayed a choleretic effect and increased the output of bile acids from liver in FEC hamsters. In addition, bile collected continuously from cannulated apple-fed animals was enriched with conjugates of cholic acid. Moreover, apple consumption lowered the lithogenic index of the bile. In response to the fruit diet, fecal excretion of bile acids and neutral sterols increased, essentially in the form of primary bile acids and sterol esters, respectively. PMID- 2244752 TI - Skin temperature and energy expenditure. AB - The value of mean skin temperature as an estimate of energy expenditure was verified in a sample of 10 normal-weight adult male subjects. Measurements were carried out with thermometric probes under conditions of rest and environmental thermoneutrality. Total heat losses were then calculated through a computerized complex mathematical formula. The value for mean energy expenditure obtained in this manner (100.2 +/- 7.02 kcal/h) is extremely close to the value for theoretical metabolism derived from the predictive equations in the literature (95.01 +/- 6.14). This verification of the validity of transforming cutaneous temperature data into energy expenditure, in accurately standardized experimental conditions, confirms the importance that the value of mean skin temperature, in the area of variability among individuals, can have in conditioning the energy balance at different levels, for a given caloric intake and with all other parameters being equal (age, sex, physical activity). In this connection, these results suggest that skin temperature may play a role in the pathogenesis of obesity. PMID- 2244753 TI - Research on secular trends in auxology. AB - Current status of research on secular trends in growth and maturation is considered from several perspectives. The need to define secular trends as positive, negative or absent is initially discussed. Positive secular trends, i.e., increases in size and earlier maturation, characterize the majority of the auxological literature. However, some populations have experienced negative secular trends or no trends. Positive secular trends and cessation of secular trends in stature and age at menarche are described for developed countries, followed by a brief discussion of secular changes in body proportions and composition. Data from developing countries illustrate all three types of secular trends. Some segments of the population show positive changes in size and age at menarche, while others show no evidence of secular change or negative secular trends. Finally, comparisons of estimated statures in earlier European populations suggest a negative secular trend, i.e., a decline in estimated stature from about the 11th to the 19th centuries, which is followed by a positive secular trend starting about the mid-19th century. PMID- 2244754 TI - [Results of the anthropologic studies of school children in Jena between 1880 and 1985]. AB - The present report is based on the results from anthropological examinations on schoolchildren, which have been carried out in Jena since 1880. The introduction to the paper gives a survey on the goals of these inquiries, followed by remarks on secular changes in selected measurements of the body (body height, body weight, chest circumference). Besides the extent of the changes in these features, the anticipation of the pubertal growth period and--by means of the relation of body height to chest circumference--a becoming slimmer of today's population of schoolchildren is documented. The comparison of the findings of 1975 and 1985 shows that, regarding the features mentioned, the acceleration in the Jena probands (although in part with reduced intensity) has lasted up to the present time. PMID- 2244755 TI - [Results of long-term studies of the development of children in Goerlitz in the last 3 decades]. AB - The author reports on the results of investigations concerning the development of 15173 girls born in Gorlitz between 1944 and 1973. With regard to maturation a significant tendency toward deceleration has been observed. Late menarche is increasing, while early menarche is decreasing. Seasonal influences on the development are discussed. September born girls, for example, are characteristic for a high menarcheal age, those born in December for a low menarcheal age. Furthermore one can assume some relations between the month of birth and the birthweight. PMID- 2244757 TI - [Sex hormone level and body shape of the !Kung San. A contribution to explaining pedomorphic stature of San populations]. AB - In order to test the hypothesis that oestrogens as well as androgens modify the body shape resp. the paedomorphous habitus of !Kung San circulating levels of sex hormones (testosterone, 5 alpha-dihydrotestosterone, and oestradiol in the serum as well as free testosterone in the saliva) of 114 healthy !Kung San men from the Northern Kalahari of Namibia were quantitatively determined by means of the radioimmunoassay method. The probands were described by 50 body measurements and morphological characters like gynaecomastia. The results show that sex hormone concentrations and body shape are significantly correlated in !Kung San men as it has been previously demonstrated for non-African samples. This does not only refer to the expression of sexual dimorphism but also to the special aspect of paedomorphism. The hypothesis of Marrett, Davies and Tobias, however, that the paedomorphous type of the San is due to "over-oestrogenization" could not be confirmed. Rather, the comparatively low testosterone level of the !Kung San men seems to be of significance. PMID- 2244756 TI - [Variations in body height within the course of a working day]. AB - Variation of body height during the day has been analyzed considering the influence of various occupations (standing, sitting, mixed) on the posture. In addition to this the following variables have been recorded on the 302 individuals under study: Sex, age, working time, time of getting up in the morning, kind of occupation, physique, sporting activities in the leisure-time, presence of defects of the spinal column, possibility of changes of the carriage at the working place and extensibility of the spinal column. The statistical analysis showed that with the exception of pathological alterations of the spinal column all these variables are influencing the variation of body height during the day. It could also be shown that the extensibility of the spinal column does not vary during the day. The author is discussing also ergonomical rules concerning the organization of working places for standing and sitting occupations. Finally some recommendations for the future organization of such places are given. PMID- 2244759 TI - Estimation of chronological age in man based on the spongy structure of long bones. AB - Estimation of chronological age in man from the spongy structure of long bones is demonstrated. The proposed method can be applied in the living and on skeletons in forensic and historical anthropology. Scoring is always based on radiographic or direct observation of structure, density and age related changes on the spongiosa and the cortex in the proximal parts of humerus and femur. On numerous cadavers of known age, sex and provenience of the Institute of Forensic Medicine of the University of Vienna, Austria, seven morphological stages were differentiated which are characteristic for seven age classes, each of ten years width. These stages are described and demonstrated graphically and in photographs. The capacity of the method is illustrated in two examples. PMID- 2244758 TI - A somatotypical study of the geographic variations between two Spanish populations. AB - Morphological differences between university students from Bilbao (Basque Country) and Madrid (Spanish Meseta) have been studied. The sample sizes are 99 and 119, respectively, and the age ranges from 18 to 22 years. The main differences between the two groups under study were observed concerning the skinfold thicknesses. Body weight, stature and limb girths do not show remarkable differences. The physiques, as judged from anthropometric somatotypes, differ in the first component (endomorphy): Basques have higher values. PMID- 2244760 TI - [Founding and significant goals and professional topics of the "Historical Anthropology" Society of East Germany]. PMID- 2244761 TI - Prevention of bacterial endocarditis. PMID- 2244762 TI - The association of selected cancers with service in the US military in Vietnam. PMID- 2244763 TI - Testing for uncommon conditions. The heroic search for positive test results. PMID- 2244764 TI - The association of selected cancers with service in the US military in Vietnam. I. Non-Hodgkin's lymphoma. The Selected Cancers Cooperative Study Group. AB - As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of non-Hodgkin's lymphoma between 1984 and 1988. All men born between 1929 and 1953 and diagnosed as having non-Hodgkin's lymphoma in an area covered by eight cancer registries were considered eligible. Control subjects were identified by random-digit dialing from these same regions and were frequency-matched to men with lymphoma by age. Analyses of 1157 men with pathologically confirmed lymphomas and 1776 control subjects showed that the risk of non-Hodgkin's lymphoma was approximately 50% higher among Vietnam veterans (odds ratio, 1.47; 95% confidence interval, 1.1 to 2.0) compared with men who did not serve in Vietnam. Vietnam veterans were also at higher risk relative to (1) men who had not served in the military, (2) other veterans, and (3) other veterans who served between 1964 and 1972. An analysis of the military histories of the 232 Vietnam veterans suggested that the relative risk (1) increased with length of service in Vietnam (P = .10), and (2) was higher among men in the sea-based Navy than among other veterans (P = .11). Little difference in risk, however, was noted according to dates of service, type of unit, military region, or any other characteristics that may have been associated with the use of Agent Orange. Although the cause remains uncertain, results of this study indicate that the risk of non-Hodgkin's lymphoma is higher among Vietnam veterans than among other men. PMID- 2244765 TI - The association of selected cancers with service in the US military in Vietnam. II. Soft-tissue and other sarcomas. The Selected Cancers Cooperative Study Group. AB - As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of soft-tissue and other sarcomas between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible. Controls were selected by random-digit dialing. Analyses of 342 men with pathologically confirmed sarcoma and 1776 controls showed that Vietnam veterans had a relative risk of 1.0 for sarcoma in comparison with men who did not serve in Vietnam (95% confidence interval, 0.6 to 1.6). Restriction of the analysis to the 254 men with soft-tissue sarcoma yielded a relative risk of 0.9 (95% confidence interval, 0.5 to 1.6). Several attributes of military service in Vietnam (eg, branch, duration of service, military region, and other characteristics that may have been associated with the use of Agent Orange) were examined, and none was associated with an increased risk for the development of sarcoma. Furthermore, no morphologic type of sarcoma was overrepresented among Vietnam veterans. Results were unchanged if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. This study, which had 97% power to detect a relative risk of 2.0 for all sarcomas, provides no evidence that the risk for the development of soft-tissue or other sarcomas is increased among veterans 15 to 25 years following service in Vietnam. PMID- 2244766 TI - The association of selected cancers with service in the US military in Vietnam. III. Hodgkin's disease, nasal cancer, nasopharyngeal cancer, and primary liver cancer. The Selected Cancers Cooperative Study Group. AB - As part of a series of investigations into the health of Vietnam veterans, we conducted case-control studies involving 310 men with Hodgkin's disease, 48 with nasal carcinoma, 80 with nasopharyngeal carcinoma, 130 with primary liver cancer, and 1776 controls between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible as cases; controls were recruited by random-digit dialing. Whereas the study had excellent power (96%) to detect a twofold increase in risk for Hodgkin's disease among Vietnam veterans, its ability to detect a similarly elevated risk in the other cancers was limited, ranging from 38% (nasal carcinoma) to 75% (primary liver cancer). Analyses showed that risks among Vietnam veterans relative to other men were 1.1 (Hodgkin's disease), 0.7 (nasal carcinoma), 0.5 (nasopharyngeal carcinoma), and 1.2 (primary liver cancer). None of these relative risks was significantly different from 1.0. Similar results were obtained if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. An examination of several attributes of military service in Vietnam (eg, branch, duration of service, and other characteristics that may have been associated with the use of Agent Orange) failed to identify any groups of veterans who were at increased risk for Hodgkin's disease. Small numbers limited further analyses of nasal, nasopharyngeal, and liver cancer. These results provide no evidence that, 15 to 25 years following service in Vietnam, the risk of these malignant neoplasms is higher among veterans. PMID- 2244767 TI - Medical house officers' knowledge, attitudes, and confidence regarding medical ethics. AB - As part of a trial of ethics education in a university-based, categorical, internal medicine training program, we surveyed all medical house officers at our institution regarding their knowledge of medical ethics, their attitudes and beliefs about selected issues in medical ethics, and their confidence in dealing with ethical problems. In a multivariate linear regression model, house officer knowledge scores were negatively correlated with postgraduate year, and positively correlated with age and with reporting a Jewish religious identity. A multivariate linear regression model predicting house officer confidence in dealing with ethical issues revealed a positive correlation with self-reported quality of ethics training in medical school and with being in the experimental group of house officers receiving ethics education. Attitudes and beliefs were largely uncorrelated with training or demographic characteristics. These results have implications for ethics education of both medical students and residents. PMID- 2244768 TI - Decision analysis, public health policy, and isoniazid chemoprophylaxis for young adult tuberculin skin reactors. AB - As part of a plan to eliminate tuberculosis in America, tuberculin skin testing was advised for all US citizens, with isoniazid chemopreventive therapy administered to appropriate positive reactors. Implementation of this plan, however, may be limited by concerns over which skin test reactors should receive isoniazid therapy. Recent decision analyses suggest that, contrary to American Thoracic Society guidelines, asymptomatic skin test reactors under age 35 years with normal chest roentgenograms and no predisposing conditions to tuberculosis reactivation will not benefit from isoniazid chemopreventive therapy. Repeated analysis of these studies reveals that calculated life expectancy depends on estimates of the probability of certain chance outcomes. If the isoniazid-related hepatitis case-fatality rate is below 1%, isoniazid chemopreventive therapy appears to be beneficial. A literature review suggests that this rate is indeed this low. If the tuberculosis case-fatality rate is above 6.7%, also supported by the literature, the advantages of isoniazid therapy are further increased. This repeated analysis should reassure physicians that isoniazid chemoprophylaxis for tuberculin skin test reactors is beneficial to the individual and consonant with public health policies. PMID- 2244769 TI - Implementing preventive services. Success and failure in an outpatient trial. AB - Physicians endorse prevention but provide only low levels of screening, health counseling, and immunization. Between 1981 and 1986, a randomized controlled trial was conducted at the Seattle (Wash) Veterans Affairs Medical Center to assess the effectiveness of the following three methods of delivery of preventive services: (1) a physician-oriented model that includes education and motivation, a chart flowsheet listing recommended activities, and periodic feedback about performance; (2) a patient education model in which patients were mailed an informative brochure advising them to ask physicians for preventive services as depicted in a patient-held pocket guide; and (3) a health promotion clinic that patients were invited to attend. A control group received their usual care. A total of 1224 male outpatients were enrolled in the trial. Baseline prevention rates for 12 age-specific prevention activities were below 25%. Neither the control group rates during the 5-year trial nor the rates for the two educational models, either singly or as a combined intervention, changed. Only the health promotion clinic model was effective, tripling prevention rates in its first year and sustaining these levels for all 5 years. It is difficult to change the clinic roles of experienced physicians and their long-term patients in a specialized multiclinic setting. Providing a separate health promotion clinic option is popular with patients, bypasses gatekeeper barriers, is reasonable in cost, and warrants wider application. PMID- 2244770 TI - Determinants of vertebral mineral density in patients receiving long-term glucocorticoid therapy. AB - This study addresses the impact of clinical and biochemical factors on the bone density of patients receiving glucocorticoid therapy. Vertebral mineral density was measured by quantitative computed tomography in 35 patients aged 17 to 77 years who had received therapeutic glucocorticoid drugs for 0.1 to 22 years. The mean (+/- SEM) vertebral mineral density z score in the subjects was -1.7 +/- 0.2. z score was unrelated to underlying diagnosis, sex, or age but was significantly related to the duration of previous steroid therapy (r = -.38) and to the total cumulative glucocorticoid dose (r = -.50). The rate of change of bone density in 16 of these subjects followed up over a period of 12 months was 8.9% and was significantly greater in subjects taking more than 12.5 mg of prednisone per day. Bone loss was not influenced by sex, age, duration of previous steroid treatment, or diagnosis and was not predictable from biochemical measures of calcium metabolism. PMID- 2244771 TI - Muscle involvement in the scleroderma syndromes. AB - Muscle involvement was identified in 14 patients with scleroderma or a connective tissue disease overlap syndrome with predominant features of scleroderma. Patients presented with symmetrical proximal weakness indistinguishable from other inflammatory myopathies. Creatine kinase and electromyography were useful to demonstrate muscle involvement. Muscle histopathology demonstrated primarily the vasculopathy of scleroderma or polymyositis in similar numbers of patients. Scleroderma vasculopathy and polymyositis generally occur without specificity to diffuse scleroderma, the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia syndrome, or an overlap syndrome with arthritis. Polymyositis also occurs when the vasculopathy of scleroderma involves other organ systems. PMID- 2244772 TI - Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women. AB - The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 "ever users." Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The "never users" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease. PMID- 2244773 TI - Impact of a public cholesterol screening program. AB - The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease. PMID- 2244775 TI - Cystocerebral syndrome. Acute urinary retention presenting as confusion in elderly patients. AB - The diagnosis of acute mental status changes in the elderly patient is often very difficult. Many causes are possible, and there is often little history obtainable. The physical examination occasionally provides the essential clues needed to discover the source of the sudden deterioration. We have recently evaluated four episodes of acute delirium in three elderly patients who presented with no readily apparent cause for these changes. On further evaluation, the patients were found to have marked bladder distention associated with acute urinary retention. None of these patients complained of discomfort, and none had any awareness or recollection of their deterioration. Each patient had rapid resolution of symptoms on bladder decompression. To our knowledge, this "cystocerebral syndrome" has not been previously described, and we suggest that it be considered in the evaluation of acute confusional states in elderly men. PMID- 2244774 TI - Spectrum of invasive Haemophilus influenzae type b disease in adults. AB - A prospective nationwide surveillance of invasive Haemophilus influenzae type b disease among adults (greater than or equal to 16 years old) was conducted in Finland during 1985 through 1988. Thirty-one cases were identified (annual incidence, 0.22/100,000). Of these infections, 71% occurred in patients with severe underlying conditions. The overall case fatality rate was 26%. Septicemia (13 patients) and pneumonia (seven patients) were the most common clinical manifestations of H influenzae type b infection; the others were epiglottitis (six patients), meningitis (three patients), and arthritis (two patients). Epiglottitis occurred in significantly younger patients, all of whom were women and four of whom were previously healthy. Subtyping of the H influenzae type b isolates according to the major outer membrane protein subtype, biotype, and lipopolysaccharide serotype showed that patterns that were uncommon (14%) among children were more common (27%) in the adults. PMID- 2244776 TI - Group B streptococcus endocarditis following second-trimester abortion. AB - An 18-year-old woman who underwent an elective second-trimester abortion developed Streptococcus agalactiae (group B streptococcus) endocarditis characterized by a large, pedunculated vegetation involving a previously normal tricuspid valve. Polyarthritic symptoms, as well as multiple pulmonary emboli, were experienced, and cure followed a course of treatment using intravenous penicillin G potassium combined with gentamicin sulfate. Endocarditis caused by this pathogen usually occurs among individuals compromised by underlying chronic disorders and, today, is a rare sequela of pregnancy and abortion. When planning therapy, consideration should be given to the possibility of tolerance among clinical isolates and the need for operative intervention in selected patients. PMID- 2244777 TI - Lymphomatoid granulomatosis presenting as ulcerodestructive gastrointestinal tract lesions in patients with human immunodeficiency virus infection. A new association. AB - We describe cases of severe odynophagia, extensive oral ulcerations, and bowel perforation in patients with human immunodeficiency virus infection that were caused by lymphomatoid granulomatosis. Such presentations in human immunodeficiency virus-infected individuals are usually ascribed to other causes and may be incorrectly treated on an empiric basis. In addition, deep tissue specimens obtained at the margin of ulcerative lesions are often necessary for definitive diagnosis. We review our limited treatment experience with zidovudine, interferon alfa, and H2 blockers in our patients. Based on the markedly increased frequency in which lymphomatoid granulomatosis is being diagnosed at our institution in the post-human immunodeficiency virus era, we postulated an association between these two entities. PMID- 2244778 TI - Toxic shock syndrome associated with use of latex nasal packing. AB - We treated a previously healthy young man who developed toxic shock syndrome 2 days after elective septoplasty with nonabsorbent latex packing. This case emphasizes that non-menstrual wound-associated toxic shock syndrome can occur after surgery that does not involve absorbent splinting or packing and should be considered in patients who present within a few days after surgery with fever, sunburnlike rash, hypotension, and multisystem complaints and laboratory abnormalities. PMID- 2244779 TI - Intrahepatic cholestasis due to hypersensitivity reaction to procainamide. AB - Hypersensitivity reactions to procainamide involving liver dysfunction are rare. We describe a patient who developed liver dysfunction after procainamide administration, manifested by fever, jaundice, elevated bilirubin concentration, and alkaline phosphatase concentration. Hepatobiliary scintigraphy demonstrated good hepatic uptake of the radionuclide without movement from hepatic parenchyma. To our knowledge, this is the first reported case of procainamide-induced intrahepatic cholestasis as demonstrated by radionuclide hepatobiliary scintigraphy. PMID- 2244780 TI - Positive-predictive value of clinical suspicion of abdominal aortic aneurysm. PMID- 2244781 TI - Where are the clinical role models? PMID- 2244782 TI - Complications of thoracentesis. PMID- 2244783 TI - Magnesium deficiency. PMID- 2244784 TI - Influence of environmental factors on 2,4-dichlorophenoxyacetic acid degradation by Pseudomonas cepacia isolated from peat. AB - A Pseudomonas cepacia, designated strain BRI6001, was isolated from peat by enrichment culture using 2,4-dichlorophenoxyacetic acid (2,4-D) as the sole carbon source. BRI6001 grew at up to 13 mM 2,4-D, and degraded 1 mM 2,4-D at an average starting population density as low as 1.5 cells/ml. Degradation was optimal at acidic pH, but could also be inhibited at low pH, associated with chloride release from the substrate, and the limited buffering capacity of the growth medium. The only metabolite detected during growth on 2,4-D was 2,4 dichlorophenol (2,4-DCP), and degradation of the aromatic nucleus was by intradiol cleavage. Growth lag times prior to the on-set of degradation, and the total time required for degradation, were linearly related to the starting population density and the initial 2,4-D concentration. BRI6001, grown on 2,4-D, oxidized a variety of structurally similar chlorinated aromatic compounds accompanied by stoichiometric chloride release. PMID- 2244785 TI - Isolation and characterization of a bacterium that mineralizes toluene in the absence of molecular oxygen. AB - A bacterium tentatively identified as a Pseudomonas sp. was isolated from a laboratory aquifer column in which toluene was degraded under denitrifying conditions. The organism mineralized toluene in pure culture in the absence of molecular oxygen. In carbon balance studies using [ring-UL-14C]toluene, more than 50% of the radioactivity was recovered as 14CO2. Nitrate and nitrous oxide served as electron acceptors for toluene mineralization. The organism was also able to degrade m-xylene, benzoate, benzaldehyde, p-cresol, p-hydroxy-benzaldehyde, p hydroxybenzoate and cyclohexanecarboxylic acid in the absence of molecular oxygen. PMID- 2244786 TI - Clostridium homopropionicum sp. nov., a new strict anaerobe growing with 2-, 3-, or 4-hydroxybutyrate. AB - From anoxic sewage sludge a new strictly anaerobic, spore-forming bacterium was isolated with 2-hydroxybutyrate as sole substrate. 2-, 3-, and 4-hydroxybutyrate, 4-chlorobutyrate, crotonate, vinylacetate, and pyruvate were fermented to acetate and butyrate. Fructose was converted to acetate, butyrate, butanol, and H2. Lactate and acrylate were fermented to acetate and propionate. Cells pregrown with lactate fermented 2-hydroxybutyrate to butyrate, propionate and acetate. No inorganic electron acceptors were reduced. The DNA base ratio was 32.0 +/- 1.0 mol% and was similar to that of Clostridium propionicum, which was determined to be 35.3 +/- 0.5 mol%. Strain LuHBu1 is described as type strain of a new species, Clostridium homopropionicum sp. nov. Another isolate obtained from marine sediment degraded 2- and 3-hydroxybutyrate to acetate and butyrate and was in some respects similar to the known species Ilyobacter polytropus. PMID- 2244787 TI - Anaerobic degradation of acetone by Desulfococcus biacutus spec. nov. AB - From anaerobic digestor sludge of a waste water treatment plant, a gram-negative, strictly anaerobic sulfate-reducing bacterium was isolated with acetone as sole organic substrate. The bacterium was characterized as a new species, Desulfococcus biacutus. The strain grew with acetone with doubling times of 72 h to 120 h; the growth yield was 12.0 (+/- 2.1) g x [mol acetone]-1. Acetone was oxidized completely, and no isopropanol was formed. In labelling studies with 14CO2, cell lipids (including approx. 50% PHB) of acetone-grown cells became labelled 7 times as high as those of 3-hydroxy-butyrate-grown cells. Enzyme studies indicated that acetone was degraded via acetoacetyl-CoA, and that acetone was channeled into the intermediary metabolism after condensation with carbon dioxide to a C4-compound, possibly free acetoacetate. Acetoacetyl-CoA is cleaved by a thiolase reaction to acetyl-CoA which is completely oxidized through the carbon monoxide dehydrogenase pathway. Strain KMRActS was deposited with the Deutsche Sammlung von Mikroorganismen, Braunschweig, under the number DSM 5651. PMID- 2244788 TI - The biotin-dependent sodium ion pump glutaconyl-CoA decarboxylase from Fusobacterium nucleatum (subsp. nucleatum). Comparison with the glutaconyl-CoA decarboxylases from gram-positive bacteria. AB - Membrane preparations of Fusobacterium nucleatum grown on glutamate contain glutaconyl-CoA decarboxylase at a high specific activity (13.8 nkat/mg protein). The enzyme was solubilized with 2% Triton X-100 in 0.5 M NaCl and purified 63 fold to a specific activity of 870 nkat/mg by affinity chromatography on monomeric avidin-Sepharose. The activity of the decarboxylase was strictly dependent on Na+ (Km = 3 mM) and was stimulated up to 3-fold by phospholipids. The glutaconyl-CoA decarboxylases from the gram-positive bacteria Acidaminococcus fermentans and Clostridium symbiosum have a lower apparent Km for Na+ (1 mM) and were not stimulated by phospholipids. In addition only the fusobacterial decarboxylase required sodium ion for stability and was inactivated by potassium ion. By incorporation of this purified enzyme into phospholipids an electrogenic sodium ion pump was reconstituted. The enzyme consists of four subunits, alpha (m = 65 kDa), beta (33 kDa), gamma (19 kDa), and delta (16 kDa) with the functions of a carboxy transferase (alpha), a carboxy lyase (beta and probably delta) and a biotin carrier (gamma). The subunits are very similar to those of the glutaconyl CoA decarboxylases from the gram-positive bacteria. With an antiserum directed against the decarboxylase from A. fermentans the alpha- and the biotin containing subunits of the three decarboxylases and that from Peptostreptococcus asaccharolyticus could be detected on Western blots. PMID- 2244789 TI - Occurrence and structure of lipoteichoic acids in the genus Staphylococcus. AB - Lipoteichoic acids were isolated from eleven species of the genus Staphylococcus using phenol-water partition and hydrophobic chromatography on octyl-Sepharose CL 4B. The lipoteichoic acids purified could be visualized by SDS-PAGE. They were shown to be composed of a hydrophilic poly(glycerophosphate) chain covalently linked to gentiobiosyldiacylglycerol, the common lipid anchor of these molecules. Glycerophosphate units of the hydrophilic chain were found to be partly substituted with ester-linked D-alanine, except in the case of S. cohnii. The lipoteichoic acids isolated from S. cohnii, S. hominis, S. saprophyticus and S. simulans contain alpha(1-2)-linked N-acetylglucosamine as an additional substituent of the poly(glycerophosphate) backbone. PMID- 2244790 TI - Natural genetic transformation of Pseudomonas stutzeri by sand-adsorbed DNA. AB - In a soil/sediment model system we have shown recently that a gram-positive bacterium with natural competence (Bacillus subtilis) can take up transforming DNA adsorbed to sand minerals. Here we examined whether also a naturally transformable soil bacterium of the gram-negative pseudomonad (Pseudomonas stutzeri) can be transformed by mineral-associated DNA. For these studies the transformation protocol of this species was further improved and characterized. The peak of competence during growth of P. stutzeri was determined to occur at the beginning of the stationary phase. The competence state was conserved during shock freezing and thawing of cells in 10% glycerol. Kinetic experiments showed that transformant formation after addition of DNA to competent cells proceeded for more than 2 h with DNA adsorption to cells being the rate limiting step. By means of the defined protocol P. stutzeri was shown to be transformed by sand adsorbed DNA. Transformation by adsorbed or dissolved DNA occurred between 16 degrees and 44 degrees C. Efficiency and DNaseI-sensitivity of transformation by DNA adsorbed to sand or in liquid were comparable. It is concluded that uptake of particle-bound DNA by P. stutzeri in soil is possible. This finding adds evidence to the view that transformation occurs in natural environments where DNA is assumed to be significantly associated with mineral/particulate material and thereby is protected against enzymatic degradation. PMID- 2244792 TI - Selection of trichloroethene (TCE) degrading bacteria that resist inactivation by TCE. AB - Two isoprene (2-methyl-1,3-butadiene) utilizing bacteria, Alcaligenes denitrificans ssp. xylosoxidans JE 75 and Rhodococcus erythropolis JE 77, were identified as highly efficient cooxidizers of TCE, cis- and trans-dichloroethene, 1,1-dichloroethene and vinyl-chloride. Isoprene grown cells eliminate chloride from TCE in stoichiometric amounts and tolerate high concentrations of TCE. PMID- 2244791 TI - The fumarate reductase operon of Wolinella succinogenes. Sequence and expression of the frdA and frdB genes. AB - The genes of the fumarate reductase of Wolinella succinogenes are organized in an operon. The three structural genes in the order frdC, frdA, frdB, are preceded by a common promoter (Kortner et al. 1990) and followed by a terminator of transcription. The proteins encoded by the genes are identical with the subunits present in the isolated enzyme. FrdA and FrdB are hydrophilic proteins consisting of 656 and 238 amino acids, respectively. The 12 cysteine residues present in FrdB form 3 ferredoxin-like clusters, whereas the 12 cysteines of FrdA are not clustered. Expression of FrdA and FrdB in Escherichia coli from a plasmid containing a DNA fragment with both genes in full length, gave rise to the EPR signals of the bi- and trinuclear iron-sulfur centers of the enzyme. Only the binuclear center was seen on the expression of FrdB together with a C-terminal fragment of FrdA (130 amino acid residues). Neither of the two centers was detected on the expression of FrdA together with a N-terminal fragment of FrdB including cysteine cluster I. Sequence comparison of FrdA and FrdB with the corresponding subunits of the fumarate reductases of E. coli or Proteus vulgaris or to those of the succinate dehydrogenases of E. coli or Bacillus subtilis revealed strong homologies (28-36% identical amino acid residues). Part of the homologous peptide stretches could be assigned to domains that are involved in the binding of the substrate of the FAD prosthetic group of the enzyme. PMID- 2244793 TI - Three-year outcomes for maintenance therapies in recurrent depression. AB - We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication. PMID- 2244794 TI - Delta sleep ratio. A biological correlate of early recurrence in unipolar affective disorder. AB - Slow wave sleep abnormalities have long been described in depression but were considered to be nonspecific indicators of psychopathology. Computerized techniques, including amplitude frequency measures and spectral analyses, are permitting new approaches to the examination of delta sleep. Early studies suggested that many depressed patients demonstrate lower delta wave intensity during the first non-rapid eye movement period than the second one. This finding, prominent in middle-aged depressed patients, has led to an examination of the ratio between the first and second non-rapid eye movement periods. This delta sleep measure seems to be a more robust predictor of recurrence than rapid eye movement latency. Analysis of data on 74 patients in a long-term maintenance treatment study for a minimum of 24 months demonstrates that the delta sleep ratio can predict survival time following discontinuation of drug treatment. Individuals with a high delta sleep ratio remain clinically remitted five times longer than those with a low delta sleep ratio. PMID- 2244795 TI - Outcome in Mania. A 4-year prospective follow-up of 75 patients utilizing survival analysis. AB - A 4-year follow-up of 75 patients was conducted to investigate outcome after recovery from an episode of mania. Predictors of an unfavorable outcome included poor occupational status prior to index episode, history of previous episodes, history of alcoholism, psychotic features and symptoms of depression during the index manic episode, male gender, and interepisode affective symptoms at 6 months' follow-up. The mortality risk during the follow-up period was 4%. The identification of specific risk factors depended on the definition of outcome and the length of follow-up. PMID- 2244796 TI - Longitudinal study of diagnoses in children of women with unipolar and bipolar affective disorder. AB - School-age children of unipolar depressed, bipolar, chronically medically ill, or normal women were diagnosed every 6 months for up to 3 years. Offspring of unipolar women had the highest rates of disorder at all evaluations, but children of bipolar and medically ill mothers also experienced significant rates of disorder. Observing diagnoses from both past lifetime and prospective follow-up assessments, it appeared that most children who had diagnoses had onsets in preadolescence and continued a chronic or intermittent course of disorder. Thus, risk to offspring of ill mothers is not transitory and indicates a pernicious course that commonly includes effective disorders alone or in combination with behavior and anxiety disorders. PMID- 2244797 TI - Two-year recall of lifetime diagnoses in offspring at high and low risk for major depression. The stability of offspring reports. AB - Stability of recall of DSM-III diagnoses was assessed at two interviews 2 years apart in a sample of 150 offspring, aged 6 to 23 years, at high and low risk for major depression. Stability of recall was good for major depression with the use of DSM-III criteria and fair for major depression with the use of "strict" criteria (based on 4 weeks' duration of illness and an impairment in a major social role). Stability of recall was good for substance abuse and conduct disorder. Stability of recall was generally poor for anxiety disorder, regardless of subtype. For all major disorders except anxiety disorder, the difference in reported age at onset between the two interviews was small (less than 1 year) and not statistically significant. The most important correlates of stability of reports of major depression were previous psychiatric treatment and dysthymia and poor social functioning at the initial interview. This is the first study to evaluate long-term recall of DSM-III lifetime diagnoses in a nonreferred sample of children, adolescents, and young adults. PMID- 2244798 TI - Rapid eye movement sleep deprivation as a probe in elderly subjects. AB - The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM "pressure" with a "ceiling effect" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD. PMID- 2244799 TI - Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. AB - The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome. PMID- 2244800 TI - Treatment of recurrent unipolar major depressive disorder. Commentary on the Pittsburgh Study. PMID- 2244802 TI - White matter abnormalities on magnetic resonance imaging in bipolar patients. PMID- 2244803 TI - Selective bowel decontamination. Less enthusiasm and more study is in order. PMID- 2244805 TI - Barotrauma associated with high-frequency jet ventilation for hypoxic salvage. AB - Most reports describe reduction in proximal airway pressures with high-frequency jet ventilation. This led us to speculate that high-frequency jet ventilation might reduce barotrauma by providing alveolar ventilation at lower airway pressures. We describe a group of patients in whom a high incidence of barotrauma was observed after institution of high-frequency jet ventilation despite reduction in measured airway pressures. Fifteen hypoxic patients who could not be treated with conventional ventilation and who had no roentgenographic evidence of barotrauma were entered into the study. Airway pressures were measured during conventional ventilation and at 2 and 24 hours after high-frequency jet ventilation. Despite significant reduction in peak inspiratory and mean airway pressures, pneumothorax developed in seven of the 15 patients, an average of 21 hours after initiation of high-frequency jet ventilation. Five patients had bilateral pneumothorax and three developed tension pneumothorax. Despite reductions in proximal airway pressures, barotrauma is a significant potential complication of high-frequency jet ventilation in patients with noncompliant lungs. We currently place bilateral prophylactic thoracostomy tubes in patients with adult respiratory distress syndrome prior to initiation of high-frequency jet ventilation. PMID- 2244801 TI - Elevation of dopamine D2 receptors in schizophrenia is underestimated by radioactive raclopride. PMID- 2244804 TI - Reappraisal of pancreatic and duodenal injury management based on injury severity. AB - We evaluated the effectiveness of treatment protocols for pancreatic and duodenal injuries according to the severity of injury. Of 81 patients, 65 survived initial injury. Pancreatic injuries without ductal involvement occurred in 21 patients and were treated by drainage. No late deaths occurred. Pancreatic injuries with ductal disruption occurred in 18 patients and were treated by pancreatic resection. Abscesses developed in seven (39%) of the patients, but no late deaths occurred. Nineteen patients had duodenal injuries without pancreatic injury, and no duodenal complications occurred. Simple closure sufficed for injuries affecting up to 40% of the duodenal circumference. Wounds affecting up to 40% of the duodenal circumference can be treated by suture closure alone. Adjunctive duodenal tube decompression should be reserved for wounds affecting greater than 40% of the duodenal circumference, closure under tension, and associated injuries to the head of the pancreas. Pyloric exclusion was rarely necessary in our patients. PMID- 2244807 TI - Percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections. AB - Operative drainage is the cornerstone of therapy for pancreatic abscess. Recently it has been suggested that successful percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections may serve as definitive therapy. We undertook therapeutic, computed tomography-directed percutaneous drainage in a selected group of 29 patients with infected pancreatic and peripancreatic fluid collections. Twenty-three patients (79%) were successfully treated with percutaneous drainage. Of six patients (21%) representing failures of percutaneous drainage, four died and two recovered after operative drainage. The four patients who died had a mean APACHE (acute physiology and chronic health evaluation) II score of 23 and five of Ranson's prognostic signs. Ranson's signs and APACHE II scores were predictive of success and mortality. We conclude that in selected patients, infected pancreatic and peripancreatic fluid collections can be treated definitively with therapeutic percutaneous catheter drainage. Based on this experience, recommendations regarding patient selection are included. PMID- 2244808 TI - Chronic alcohol ingestion increases aortic lipid levels in rats. AB - We evaluated the effects of alcohol ingestion on aortic lipid concentrations in 15 pair-fed Sprague-Dawley rats divided into three groups of five animals each. Control rats were fed a liquid diet, with 36% of their energy provided by maltose dextrin for 28 days, and the remaining two groups of rats were fed an equivalent proportion of their energy as alcohol for 28 days or 18 months. Alcohol-fed rats exhaled significantly greater quantities of ethane than did controls at 28 days and 18 months. Serum cholesterol levels increased by 40% and triglyceride levels increased by 80%, but phospholipid levels remained unchanged in alcohol-fed rats compared with controls. Aortic concentrations of cholesterol and phospholipids increased twofold and threefold, respectively, in alcohol-fed rats, with a corresponding alteration of the cholesterol-phospholipid ratio at both time intervals. Tissue triglyceride levels were only elevated at 28 days, and no differences in aortic lipid peroxide levels were detected between alcohol-fed rats and controls. The results of the study indicate that alcohol ingestion increases aortic cholesterol, phospholipid, and triglyceride levels at 28 days and cholesterol and phospholipid but not triglyceride levels at 18 months. The mechanisms underlying the accumulation of lipids in aortic tissue need further elucidation. PMID- 2244806 TI - Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist. AB - Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial. PMID- 2244809 TI - Mortality and quality of life after total abdominal colectomy. AB - We have reviewed the results of 107 consecutive total abdominal colectomies performed at our institutions during the past 10 years. Indications for surgery were carcinoma of the colon (60), multiple polyps (nine), diverticular disease (31), and other conditions (seven). Seven (6.5%) were emergency operations. All patients had anastomosis of the terminal ileum into the lower rectum or distal sigmoid colon no more than 25 cm above the anus. Thirty days after surgery, two patients (1.8%) had died of complications of anastomotic leaks. Both were poor candidates for primary reanastomosis. Morbidity was low, occurring in 11 patients (10.3%). Follow-up evaluation of bowel function revealed satisfactory results in 102 patients (95%). Five patients (5%) had experienced chronic debilitating diarrhea. Unfavorable results were more common with diverticular disease than with neoplasia. PMID- 2244811 TI - Does somatostatin analogue prevent experimental acute pancreatitis? AB - Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201 995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis. PMID- 2244810 TI - The influence of renal function on diabetic foot ulceration. AB - We examined the effect of renal function on the formation, severity, and outcome of diabetic foot lesions. Information was collected from a retrospective hospital chart survey and analyzed by univariate and multivariate linear regression analysis. Creatinine clearance, peripheral neuropathy, and peripheral vascular disease were all found to be independently associated with formation of foot lesions, indicating that each of these acts by distinct biologic mechanisms. Renal function had no bearing on the severity of lesions or on their eventual healing. We conclude that foot ulcers are more likely to develop in diabetic patients who also suffer from renal impairment, but they are no less likely to heal than are those in patients with normal renal function. We further conclude that attempts to preserve functional limbs in these patients are justified. PMID- 2244812 TI - Venous hemodynamics in a chronic venous valvular insufficiency model. AB - To develop a large-animal model of chronic venous valve incompetence, 13 greyhound dogs underwent unilateral hindlimb venous valve lysis with a valve cutter apparatus pulled retrograde through the iliac, femoral, and lateral saphenous veins. Bilateral venous pressures in the lateral saphenous vein were recorded before valve lysis, immediately after valve lysis, and at intervals from 1 to 14 weeks after valve lysis, with the dogs in the supine position and elevated 80 degrees semierect, as well as after stimulated hindlimb muscle contraction to empty the hindlimb veins. Passive venous filling time with elevation and 90% venous refilling time after muscle contraction were calculated. From immediately after through 14 weeks after valve lysis, a shortened venous filling time and 90% venous refilling time as well as an elevated poststimulation venous pressure were noted. This valve lysis method successfully produced a hemodynamically verified model of venous valvular insufficiency. PMID- 2244813 TI - Generation of human monoclonal antibodies against colon cancer. AB - Lymphocytes from regional lymph nodes of patients with colon cancer were fused with a human lymphoblastoid cell line with or without in vitro immunization. The efficacy of these two protocols for the generation of human monoclonal antibodies against colon cancer was investigated. The hyperplastic lymph nodes adjacent to the tumor were the best source of B lymphocytes. Fusion frequency and the number of tumor-reactive clones were markedly increased when the in vitro immunization protocol was applied prior to fusion. As a stimulant in in vitro immunization, the supernatant of pokeweed mitogen-stimulated T lymphocytes was superior to the supernatant of mixed lymphocytes culture. Carcinoembryonic antigen at 20 micrograms/L seemed to be the optimal dose for in vitro immunization. The reactivities of human monoclonal antibodies thus generated were measured by enzyme-linked immunosorbent assay and confirmed by immunoperoxidase staining. Combining in vitro immunization with lymphocytes of cancer patients may lead to the successful production of clinically useful human monoclonal antibodies. PMID- 2244814 TI - Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3. AB - B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients. PMID- 2244816 TI - Cardiac risk in vascular surgery. The oral dipyridamole-thallium stress test. AB - The value of the oral dipyridamole-thallium stress test in identifying patients at high risk of myocardial infarction after vascular procedures has not been documented. We studied prospectively 46 patients who underwent an oral dipyridamole-thallium stress test before undergoing vascular operations. Twenty patients (43%) had a positive test result, defined by a thallium defect with reperfusion, while 26 patients had a negative test result. Myocardial infarctions were documented postoperatively in 5 (25%) of 20 of the group with positive results and 1 (4%) of 26 of the group with negative results. Three of the six myocardial infarctions were clinical; all three were in the group with positive results. No correlation was identified between dipyridamole-thallium stress test results and clinical cardiac history. A positive dipyridamole-thallium stress test result is a more sensitive predictor of postoperative myocardial infarction than ejection fraction or history of coronary artery disease. The oral dipyridamole-thallium stress test is as useful as the intravenous test in this setting. PMID- 2244815 TI - Calcium and calcium binding in human gallstone disease. AB - Precipitation of calcium salts from bile is important in pigment gallstone formation and may serve as a nidus for cholesterol precipitation. We compared gallbladder bile from patients with symptomatic gallstone disease (40 with cholesterol gallstones and 12 with pigment gallstones) with bile from 10 patients undergoing surgery for non-biliary tract disease. Bile from patients with gallstone disease was less concentrated, with decreased sodium, bile salt, and phospholipid concentrations, but elevated biliary calcium concentrations were not observed. The relationship between free ionized calcium and total calcium was similar in all groups, indicating no difference in calcium binding by gallstone containing bile. We cannot exclude elevated biliary calcium level as a factor in gallstone pathogenesis, as it could be a transient event. The importance of calcium precipitation was supported by our finding that more than half of the samples were saturated or supersaturated with at least one calcium salt, calcium carbonate. PMID- 2244817 TI - The natural history of intimal flaps in a canine model. AB - The natural history of arterial intimal flaps has not been well defined. This study characterizes the natural history of unrepaired intimal flaps. Thirty-nine 1-, 2-, and 3-mm hemispheric, distally based intimal flaps were made in 4- to 5 mm diameter canine femoral and carotid arteries. Twenty arteries had 2- and 3-mm intimal flaps and were monitored for short-term arterial thrombosis and flap extension. Nineteen had 1- and 2-mm intimal flaps and were monitored for thrombosis, long-term development of neointimal hyperplasia, arterial stenosis, and persistence of the flap. While 40% of the arteries with 3-mm intimal flaps developed thrombosis in 3 to 5 days, only 3% of the arteries with 1- or 2-mm intimal flaps developed thrombosis. Most 1- to 2-mm intimal flaps resolved and the subsequent development of neointimal hyperplasia or arterial stenosis was minimal. Arteries with hemodynamically significant stenoses from intimal flaps warrant repair, while arteries with smaller intimal flaps may not require repair. PMID- 2244818 TI - The effects of shear stress on endothelial cell retention and function on expanded polytetrafluoroethylene. AB - We evaluated the adherence of indium 111-radiolabeled endothelial cells to fibronectin-treated expanded polytetrafluoroethylene surfaces exposed to high (437 s-1) vs low (218 s-1) shear and the influence of shear on prostacyclin production. Canine jugular vein factor VIII-positive endothelial cells in passages 3 through 6 were incubated with 111Indium-oxine, and labeled cells were seeded onto fibronectin-treated expanded polytetrafluoroethylene patches. Patches with confluent cells were exposed to shear in a Weissenberg rheogoniometer for intervals ranging up to 60 minutes. Percent endothelial cell retention was determined by gamma counting of patches and media and by histologic evaluation. Prostacyclin production (tritiated radioimmunoassay of 6-keto-prostaglandin F1 alpha) was assayed on perfusing media. Results showed no differences in 6-keto prostaglandin F1 alpha production between shear rates or time periods. Endothelial cell retention did not differ between the shear rates. Rotational shear caused persistent cell loss over time in either high- or low-shear conditions. This persistent cell loss in response to steady rotational shear differs from that in response to identical rates of pulsatile linear shear in our laboratory where cell loss approached zero after 15 minutes. PMID- 2244819 TI - Surgical aspects of sclerosing encapsulating peritonitis. AB - Sclerosing encapsulating peritonitis (SEP) is associated with the administration of beta-blocking agents as well as continuous ambulatory peritoneal dialysis. The predisposing factors in the latter group are recurrent peritonitis, presence of acetate in the dialysate, and antiseptics used during bag exchanges. We report a case of SEP following chronic ambulatory peritoneal dialysis and review the literature on this benign yet potentially lethal condition. Sclerosing encapsulating peritonitis frequently leads to intestinal obstruction, small-bowel necrosis, enterocutaneous fistulas, and malnutrition. There is a high incidence of anastomotic failure when a resection and primary intestinal anastomosis is performed in patients with SEP. Although SEP is not commonly reported in the surgical literature, its importance to surgeons is indicated by the fact that the overall mortality rate is close to 60% in patients with SEP who develop surgical complications. PMID- 2244820 TI - Resident training. PMID- 2244822 TI - Causes of proliferative retinopathy following pneumatic retinopexy. PMID- 2244823 TI - Yersinia infection in acute anterior uveitis. PMID- 2244824 TI - Contact ultrasonography and hypotonous eyes. PMID- 2244821 TI - Retinoblastoma incidence in the United States. PMID- 2244825 TI - Ultrasonography with nonophthalmic equipment. PMID- 2244826 TI - Spontaneous involution of a choroidal osteoma. PMID- 2244827 TI - Eyelid creaser. PMID- 2244828 TI - Laceration of the globe due to a blow-out fracture. PMID- 2244830 TI - Hypothesis concerning carbonic anhydrase treatment of cystoid macular edema: example with epiretinal membrane. PMID- 2244829 TI - Micrococcus endophthalmitis. PMID- 2244831 TI - Leiomyosarcoma metastatic to the orbit. PMID- 2244832 TI - Johns Hopkins outcome study for cataract management. PMID- 2244833 TI - Corneal epithelial and stromal reactions to excimer laser photorefractive keratectomy. I. Concerns regarding the response of the corneal epithelium to excimer laser ablation. PMID- 2244835 TI - Corneal epithelial and stromal reactions to excimer laser photorefactive keratectomy. III. The excimer laser and radial keratotomy: two vastly different approaches for myopia correction. PMID- 2244834 TI - Corneal epithelial and stromal reactions to excimer laser photorefractive keratectomy. II. Unpredictable corneal cicatrization. PMID- 2244836 TI - The influence of prior therapy on the success of trabeculectomy. AB - The role of early surgery in the management of primary open angle glaucoma is under debate. To determine whether previous medical therapy influences the outcome of subsequent trabeculectomy, we retrospectively reviewed the results of surgery in two groups of patients. The first group underwent primary trabeculectomy, having had an average of 2 weeks of preoperative medical therapy, and this group was compared with a group of patients who had received at least 1 year of topical glaucoma therapy before undergoing trabeculectomy (the multiple treatment group). The two groups were similar in terms of a number of variables, including race, age, sex, presenting intraocular pressures, and presenting visual fields, and they differed only in the known duration of their disease. The success rate of trabeculectomy was significantly higher in the primary trabeculectomy group as compared with that in the multiple-treatment group (P less than .001). We discuss the possible reasons for this difference and its implications for the future management of primary open angle glaucoma. PMID- 2244837 TI - Early intraocular pressure rise after trabeculectomy. AB - Intraocular pressure (IOP) was measured 4 to 6 hours after surgery and on the first postoperative day in 35 eyes of 35 consecutive patients undergoing initial trabeculectomy. In 27 eyes, the anterior chamber was re-formed at the completion of surgery with balanced salt solution, and in eight eyes it was reformed with hyaluronate sodium. A total of six eyes (17%) had an IOP of 40 mm Hg or greater 4 to 6 hours after surgery. Patients who received hyaluronate to maintain the depth of the anterior chamber had a significantly greater chance of experiencing a marked postoperative IOP rise, both at 4 to 6 hours (P = .005) and on the first postoperative day (P = .0038). There was no correlation between the postoperative IOP rise and the patient's age, sex, glaucoma diagnosis, preoperative IOP, use of 5-fluorouracil, or the number of sutures used to close the scleral flap. Hyaluronate may contribute to an early increase in IOP that could result in further visual field loss in eyes with severe glaucomatous damage. We recommend early monitoring of IOP after trabeculectomy and avoiding the routine use of hyaluronate. PMID- 2244838 TI - Serous retinal detachment following glaucoma filtering surgery. AB - We report the occurrence of serous retinal detachment in association with choroidal effusion and hypotony in six eyes that had undergone glaucoma filtering surgery. Hypotony with choroidal effusion was documented in five patients before the onset of serous retinal detachment. While one patient underwent vitrectomy, treatment was conservative in the other patients. Serous retinal detachment and choroidal effusions resolved spontaneously as the intraocular pressure normalized. Although one patient regained preoperative visual acuity, all other patients lost at least one line of Snellen acuity. PMID- 2244839 TI - The macular photostress test in diabetic retinopathy and age-related macular degeneration. AB - We propose the macular photostress test for the evaluation of macular function in the office setting. Eighty eyes were tested and divided into four diagnostic categories: background diabetic retinopathy, diabetic macular edema, age-related macular degeneration, and normal. The recovery times for the eyes with age related macular degeneration were longer than for eyes with macular edema (P = .03). Age-matched patients with age-related macular degeneration had longer recovery times than did those without age-related macular degeneration (P = .0001). A possible explanation is that the prolonged recovery time in the eyes with age-related macular degeneration reflects that the anatomic lesion is located in the retinal pigment epithelium-photoreceptor complex. In comparison, the eyes with macular edema, whose lesion is in the inner retina and not the retinal pigment epithelium, show a less-prolonged recovery time than the eyes with age-related macular degeneration. PMID- 2244840 TI - Surgical techniques and reattachment rates in retinal detachment due to macular hole. AB - We evaluated reattachment rates of the transvitreal and transscleral techniques for treating 250 eyes with retinal detachment due to macular hole. The initial success rate of the transvitreal approach was 56% (53/94). There was no difference between the results of gas tamponade alone and vitrectomy and gas tamponade. The initial success rate of the transscleral approach was 83% (130/156). Macular diathermy and macular buckling showed a higher reattachment rate than macular diathermy alone. The final success rates were the same (95%), regardless of which approach was selected as an initial technique. The patients whose initial transvitreal reattachment failed and who underwent additional transvitreal procedures (including macular laser photocoagulation) showed a success rate of 93%. We believe that gas tamponade, which has possibility of better visual prognosis, should be selected as an initial technique because the final success rate was found to be the same regardless of the initial surgical techniques. PMID- 2244841 TI - Optic nerve hypoplasia. Identification by magnetic resonance imaging. AB - High-resolution magnetic resonance images of the intracranial optic nerves and chiasm were obtained in 15 patients with severe optic nerve hypoplasia. These were compared, in a double-blind manner, with similar images from 30 age-matched controls. On both coronal and sagittal images, hypoplastic optic nerves were thin and demonstrated signal attenuation when compared with normal optic nerves. All patients with severe bilateral optic nerve hypoplasia also had diffuse chiasmal hypoplasia, which was seen best on coronal images. Patients with unilateral or asymmetrical optic nerve hypoplasia had variable chiasmal abnormalities. The degree to which the magnetic resonance diagnosis of optic nerve hypoplasia matched the clinical diagnosis was highly significant (P less than .001, Fisher's Exact Test) for both coronal and sagittal views of the intracranial optic nerves. Oblique axial and coronal views of the orbital optic nerves did not reliably distinguish optic nerve hypoplasia from normal optic nerves. High-resolution magnetic resonance imaging is a useful diagnostic modality to identify small optic nerves neuroradiologically. PMID- 2244842 TI - Graves' ophthalmopathy. Correlation of saccadic eye movements with age, presence of optic neuropathy, and extraocular muscle volume. AB - Quantitative infrared oculography was used to record saccadic eye movements of 49 patients with Graves' ophthalmopathy. Peak saccadic velocities were decreased in those patients who developed or presented with optic neuropathy. This effect was more pronounced for larger eye movements. Peak saccadic velocity also decreased as total extraocular muscle volume and limitation of ocular motility increased. For any given extraocular muscle volume, peak saccadic velocity was 40 degrees/s slower in patients 40 years or older than in younger patients. The relationship between velocity and motility limitation was most pronounced for intermediate muscle volumes (8% to 15% of total orbital volume). Saccadic velocities in those patients with optic nerve compression often improved following treatment. This study demonstrated that eye movement recording was a useful adjunct in evaluation of patients with Graves' ophthalmopathy. Furthermore, age-related lowering of peak saccadic velocities implicated changes of extraocular muscle structure as a factor in the development of optic neuropathy. PMID- 2244843 TI - Ticlopidine treatment reduces the progression of nonproliferative diabetic retinopathy. The TIMAD Study Group. AB - The Ticlopidine Microangiopathy of Diabetes study (TIMAD), a randomized, double masked, placebo-controlled trial, assessed the effect of this antiplatelet agent (ticlopidine hydrochloride) in reducing the progression of nonproliferative diabetic retinopathy in 435 patients followed up for 3 years. The mean yearly increase in definite microaneurysms on fluorescein angiograms was significantly higher (P = .03) in the placebo group (1.44 +/- 4.67) than in the ticlopidine group (0.48 +/- 5.79). Significance was limited to primary analysis using a quality angiographic coefficient for definite microaneurysms in patients with at least three readable angiograms over a 3-year period. Ticlopidine was significantly beneficial to insulin-treated diabetic patients, inducing a sevenfold reduction of the yearly microaneurysm progression (0.23 +/- 6.66) compared with the placebo (1.57 +/- 5.29) (P = .03). Among insulin-treated diabetic patients, fewer had development of new vessels in the ticlopidine group than in the placebo group, at borderline statistical significance (P = .056). Overall retinopathy progression was significantly less severe in the ticlopidine group (P = .04). Adverse reactions associated with ticlopidine included neutropenia (severe in one patient) with no clinical complications, diarrhea, or rash. This study demonstrated that ticlopidine slows down the progression of nonproliferative diabetic retinopathy. PMID- 2244844 TI - Metastatic ciliary body carcinoid tumor. AB - A 50-year-old man with a history of systemic carcinoid had decreased right eye vision and a darkly pigmented cilio-choroidal mass. Results of ultrasonographic and fluorescein angiographic examinations were consistent with a malignant melanoma. Fine-needle aspiration biopsy of the lesion identified it as a carcinoid metastasis. The patient refused both radiation and enucleation; complete excision with a cyclochoroidectomy was performed. Histopathologic examination showed a carcinoid neoplasm covered by marked hyperplasia of the retinal pigment epithelium that produced the pigmented appearance of the lesion. PMID- 2244845 TI - Absorption of 308-nm excimer laser radiation by balanced salt solution, sodium hyaluronate, and human cadaver eyes. AB - Absorption of the excimer laser radiations of 193-nm argon fluorine and 308-nm xenon chloride in balanced salt solution, sodium hyaluronate, and human cadaver eyes was measured. The absorption of these materials as considerably different for the two wavelengths; we found that 308-nm light experienced much less absorption than the 193-nm light. The extinction coefficient (k) for 308 nm was k = 0.19/cm for balanced salt solution and k = 0.22/cm for sodium hyaluronate. In contrast to this, the extinction coefficient for 193 nm was k = 140/cm for balanced salt solution and k = 540/cm for sodium hyaluronate. Two 1-day-old human phakic cadaver eyes showed complete absorption with both wavelengths. Using aphakic eyes, incomplete absorption was noted at the posterior pole with 308 nm and complete absorption was noted with 193 nm. The extinction in the anterior part of aphakic eyes (the first 6 mm) was 4.2/cm for 308 nm, meaning that the intensity of the light is reduced by a factor of 10 after traveling the first 5.5 mm. However, we observed that the material in the eye fluoresces, meaning the 308 nm is transformed into other (longer) wavelengths that travel through the total eye with minimal absorption. Conclusions drawn from this experiment are that the use of the 308-nm wavelength may have undesirable side effects, while the use of the 193-nm wavelength should be consistent with ophthalmic use on both the cornea and the lens. PMID- 2244846 TI - Hydrogen peroxide localization in experimental optic neuritis. AB - The association of reactive oxygen species to altered permeability of the blood brain barrier in acute experimental encephalomyelitis was investigated by ultrastructural cytochemical localization of hydrogen peroxide (H2O2) to sites in the optic nerve previously identified by extravasation of intravascular horseradish peroxidase. Using a modified cerium method, we found electron-dense cerium-derived H2O2 reaction product was localized to the perivascular space at the lamina retinalis, lamina choroidalis, and lamina scleralis. In the optic nerve head, electron-dense reaction product was observed in the presence of intravascular leukocytes, although adjacent perivascular and interstitial inflammatory cells at this site were scant. In the myelinated retrobulbar optic nerve, cerium-derived H2O2 reaction product was seen in the intravascular space of blood vessels and surrounding perivascular and interstitial foci of inflammatory cells. Reaction product was also observed in the extracellular space adjacent to the plasmalemma of axons and glial cells in the optic nerve head and retrobulbar nerve. The perivascular and intravascular distribution of cerium derived reaction product suggests that H2O2 may play a role in the pathogenesis of altered vascular permeability in experimental optic neuritis and supports our previous observations of suppression of blood-brain barrier permeability by detoxification of H2O2 with the exogenous administration of antioxidant enzymes. PMID- 2244848 TI - Whitnall's sling for poor function ptosis. AB - Severe unilateral ptosis with poor levator function has previously been treated with maximal levator muscle resection or bilateral or unilateral frontalis suspension. One of us (R.L.A.) has developed a technique called "Whitnall's sling," where only the levator aponeurosis is resected, preserving Whitnall's ligament and its attachments. Whitnall's ligament and the underlying resected levator muscle are sutured to the superior portion of the tarsal plate. This surgery preserves levator muscle, Muller's muscle, and Whitnall's ligament without altering the structures that produce the three-layer tear film. In 69 eyelids operated on between July 1976 and July 1986, in which a minimum of 1 year of follow-up by one of use was obtained, results have been satisfactory and directly related to levator function. We believe this technique to be anatomically and physiologically superior to "maximal levator resection" with similar long-term results. More recent results have shown that the addition of a 5-mm superior tarsectomy provides an additional elevation of 1 to 1.5 mm. Whitnall's sling is best suited for cases where the opposite fissure height is 9 mm or less and levator function of the ptotic eyelid is 3 to 5 mm. PMID- 2244847 TI - Scleral buckling and ocular rigidity. Clinical ramifications. AB - Ocular rigidity is the change in intraocular pressure produced by an incremental change in intraocular volume. Ocular rigidity was determined in 14 donor eyes by injecting small increments of a balanced salt solution through the limbus, while continually monitoring the intraocular pressure with a transducer. A buckling procedure was then performed in these eyes with the use of various solid silicone or stainless steel encircling elements, and the experiments were repeated. Buckled eyes were significantly less rigid than unbuckled eyes, and eyes with higher buckles were significantly less rigid than those with shallower buckles. The observed changes in rigidity are likely secondary to changes in the shape and stress distribution of the scleral shell and are only to a small degree related to the elasticity of the encircling element. Greater volumes of vitreous substitutes, gases, or antibiotics may be injected into buckled eyes compared with unbuckled eyes before excessive intraocular pressures are reached. PMID- 2244849 TI - The Blepharochalasis syndrome. PMID- 2244850 TI - Dysregulation of lipid metabolism in Tangier monocyte-derived macrophages. AB - The cellular defect in Tangier mononuclear phagocytes (MNP) was shown to be associated with significant abnormalities in cellular phospholipid, triglyceride, and cholesteryl ester metabolism by using various radiolabeled precursors (32Pi, 3H-serine, 3H-choline, 14C-acetate, and 14C-oleic acid). Tangier MNP expressed increased rates of synthesis for phospholipids (twofold), triglycerides (fivefold), and cholesteryl esters (threefold) as compared to normal MNP when incubated in McCoy's medium containing 0.2% human serum albumin. The turnover rate of cellular phospholipids was also enhanced, while the turnover rates for triglycerides and cholesteryl esters were normal, thus leading to the accumulation of a larger pool of labeled triglycerides and cholesteryl esters in Tangier MNP. The individual phospholipid classes, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine were similarly affected. Cholesterol loading led to approximately 30% down-regulation of phospholipid synthesis in normal cells, but Tangier MNP showed a smaller response. When nonloaded normal MNP were exposed to high density lipoprotein3 (HDL3), they diminished cellular cholesterol esterification mediated by acyl CoA:cholesterol acyltransferase (ACAT); in Tangier MNP, ACAT activity increased in the presence of HDL3. When cholesterol-loaded normal and Tangier MNP were treated with HDL3, an up-regulation of phospholipid synthesis was observed in both cell types, but Tangier MNP showed a smaller response. We conclude that the defect in Tangier disease, which we recently described as a "disorder of intracellular traffic" (Schmitz et al. Proc Natl Acad Sci USA 1985;82:6305-6309), is associated with a dysregulation of cellular lipid metabolism, leading to an overproduction of triglycerides and esterified cholesterol and to enhanced synthesis and catabolism of phospholipids. PMID- 2244851 TI - High density lipoprotein cholesterol. A 16-year longitudinal study in aging male twins. AB - The National Heart, Lung, and Blood Institute Twin Study is a collaborative, longitudinal study of white, male twins who were veterans of World War II and were born between 1917 and 1927. The twins were selected from the National Academy of Sciences/National Research Council Twin Panel and were examined three times (1969-73, 1981-82, and 1986-87). At all three exams, the dizygotic (DZ) twins were found to have a greater total variance for high density lipoprotein cholesterol (HDL-C) than the monozygotic (MZ) twins (p less than 0.05). DZ variance estimates were also larger than the variance of singletons from the second National Health and Nutrition Examination Survey. At the third exam, HDL-C was divided by precipitation into HDL2 and HDL3 fractions, and HDL2 was found to be the primary cause of the greater DZ total variance (DZ/MZ HDL2 variance = 2.22). The DZ/MZ variance ratio decreased 9% after adjustment of HDL2 for correlations with plasma triglycerides, alcohol consumption, smoking, exercise, and body mass index measured at the third exam. Postulated causes of the difference between MZ and DZ total variances include World War II induction screening, environmental influences unique to one zygosity, and genetic factors related to twinning. Further understanding of the etiology of this striking difference between MZ and DZ twin variance for HDL-C fractions could lead to more effective methods of decreasing the complications of arteriosclerosis. PMID- 2244852 TI - Relationship between high density lipoprotein subfractions and coronary risk factors in a rural white population. AB - The relationship of serum high density lipoprotein cholesterol (HDL-C) levels and of the HDL2-C and HDL3-C subfractions to several factors associated with coronary risk was examined in a cross-sectional study, which included 655 men and 731 women ages 20 to 64 years. Participants with coronary heart disease (CHD) had lower levels of HDL-C, HDL2-C, and HDL3-C; however, only HDL-C in women was significant. Maleness, body mass index, triglyceride levels, tobacco use, and carbohydrate intake (in men) were significantly inversely related to total HDL-C, while alcohol intake was significantly positively related to HDL-C. The associations were stronger for HDL2-C than for HDL3-C, except that alcohol intake in men was more strongly related to HDL3-C. The findings of this study suggest that several factors that influence CHD risk do so in part through modifying HDL2 C levels. PMID- 2244853 TI - Whole blood impedance platelet aggregometry and ischemic heart disease. The Caerphilly Collaborative Heart Disease Study. AB - The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men who were ages 49 to 64 years at the time of the study. We report the results for platelet aggregation measured in whole blood from a subsample of 308 men. The index of sensitivity used was the minimum concentration of adenosine diphosphate that produced a defined degree of impedance change in the Chronolog 560 aggregometer. There was a marked association between aggregation and prevalent ischemic heart disease (IHD). The odds ratios and 95% confidence intervals (CI) for prevalent IHD in men with the most sensitive platelets compared with those with the least sensitive platelets were 3.6 (95% Cl: 1.1 to 12.2) for angina; 7.3 (95% Cl: 2.0 to 24.3) for previous myocardial infarction (MI); and 2.7 (95% Cl: 1.0 to 7.6) for electrocardiogram evidence of ischemia. The confidence limits for these odds ratios are large because of the small sample size, but the estimates of odds ratio are relatively large compared to similar relationships between the traditional risk factors of serum cholesterol, blood pressure, smoking, and prevalent IHD (1.5 to 2.5). A number of factors that might confound the relationships between platelets and IHD were examined, but the associations remained statistically significant when these were taken into account. PMID- 2244854 TI - Analysis of indium-111 platelet kinetics and imaging in patients with aortic grafts and abdominal aortic aneurysms. AB - To quantitatively characterize processes of platelet thrombus formation in vivo, the kinetics and incorporation into thrombus of autologous In-111-labeled platelets were compared in six patients with aortic aneurysms and in seven patients with prosthetic aortic grafts. Although platelet survival was comparably shortened in both patient groups (mean, 5.8 days), the maximum radioactivity (percentage of whole body radioactivity) as determined by gamma camera imaging was higher in the aneurysms than in the grafts (3.3% +/- 1.6% vs. 1.6% +/- 1.1%, p = 0.05). Maximum In-111 uptake was also attained more quickly in the aneurysm patients (2.3 +/- 0.8 days vs. 3.5 +/- 1.3 days; p = 0.07). The experimental platelet kinetic and imaging data were subsequently evaluated by compartmental analysis to estimate both normal and disease-related components of platelet destruction. This analysis indicated that deposited platelet radioactivity had a longer residence time on grafts (2.9 +/- 1.7 days vs. 1.4 +/- 0.9 days, p = 0.07) but accumulated at a faster rate in aneurysms (5.0% +/- 3.4% per day vs. 1.4% +/- 0.9% per day, p = 0.02). As determined by imaging, only a proportion of increased platelet destruction was specifically due to the aneurysms (55% +/- 38%) or grafts (17% +/- 11%, p = 0.03). This result indicates additional components of platelet destruction unrelated to graft and aneurysm thrombus formation which, in some graft patients, may reflect a greater severity of vascular disease or other mechanisms causing a preferential shortening of platelet survival. Thus, the analytical approach described may be a useful one for discriminating components of in vivo platelet utilization including platelet removal due to normal hemostatic and senescent mechanisms, localized thrombus formation, and more generalized vascular disease. PMID- 2244855 TI - Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. AB - Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen-deficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n = 17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n = 20), and 3) continuously administered 17-beta estradiol (n = 18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one-half) in animals in both hormone replacement groups (p less than or equal to 0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subfraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women. PMID- 2244856 TI - Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein. AB - Clinical studies have demonstrated an impaired fibrinolytic function in patients with angiographically ascertained coronary artery disease or previous myocardial infarction. This decreased fibrinolytic function is to a major extent explained by the presence of high plasma levels of plasminogen activator inhibitor-1 (PAI 1) and is most common in patients with hyperlipoproteinemias type IIB and IV. To further investigate the association between hypertriglyceridemia and elevated plasma levels of PAI-1, cultured human umbilical vein endothelial cells were exposed to purified lipoproteins isolated from normo- and hypertriglyceridemic (NTG and HTG) individuals. We found that very low density lipoprotein (VLDL) from both NTG and HTG subjects stimulated the secretion of PAI-1 from endothelial cells in a dose-dependent manner. HTG-VLDL at a concentration of 100 micrograms/ml gave rise to a 73% increase in PAI-1 secretion as compared to control cultures, whereas NTG-VLDL only gave rise to a 30% increase (p less than 0.05), indicating that HTG-VLDL is a more potent stimulus to PAI-1 secretion than is NTG-VLDL. Experiments in which endothelial cells were exposed to VLDL subfractions indicated that large VLDL particles, in particular, induce PAI-1 release. Binding experiments demonstrated a specific cellular binding of both NTG and HTG-VLDL to the cells, but HTG-VLDL bound about four times more effectively than NTG-VLDL. Exposure of the endothelial cells to an LDL receptor antibody was found to block 75% (p less than 0.005) of the VLDL-induced secretion of PAI-1 from the cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2244857 TI - Abnormal composition of hypertriglyceridemic very low density lipoprotein determines abnormal cell metabolism. AB - The metabolism of very low density lipoprotein (VLDL) from normolipemic (NTG) subjects, hypertriglyceridemic (HTG) subjects, and hypertriglyceridemic subjects treated with bezafibrate (BZ) was studied in cultured human skin fibroblasts. The binding, cell association, and proteolytic degradation of 125I-labeled lipoproteins and the capacity to regulate cellular sterol synthesis was determined with and without maximal stimulation of the lipoprotein by exogenous recombinant or plasmatic apolipoprotein (apo) E-3. The VLDL was separated into three density subfractions: I, II, and III. Multiple differences between HTG and NTG lipoproteins were found, which all reverted toward normal with therapy. Even in the presence of an optimal concentration of apo E-3, HTG-VLDL demonstrated 100% to 200% higher metabolic activities, indicating a better association or a better biological expression of apo E-3 at the surface of the lipoprotein. There was a strong and linear relationship between the cholesterol ester/protein ratios of the different VLDLs and their proteolytic degradations by the cells (r = 0.95). Thus, the composition/structure alterations of VLDL appear to determine their apo E-3-dependent cellular catabolism. In addition, HTG-VLDLs not enriched with apo E-3 exhibited a capacity to down-regulate cellular sterol synthesis independently of their uptake and degradation by the cells. This abnormality appeared to reflect the ability of the VLDL to donate cholesterol to the cells and was not observed in receptor-negative cells. Thus, HTG-VLDL is much more capable than NTG-VLDL of introducing cholesterol to cells by at least two mechanisms: 1) accelerated uptake and degradation and 2) direct transfer of cholesterol to the cells. Both processes are potentially atherogenic and are reversible when triglyceride-lowering therapy is instituted. PMID- 2244858 TI - Effect of dietary fish oil on coronary artery and aortic atherosclerosis in African green monkeys. AB - Studies were carried out for 2.5 to 3 years in adult male African green monkeys (grivet subspecies) fed diets containing 22% of calories as lard or fish oil with 40% of calories as fat and 0.75 mg cholesterol/Kcal to determine if isocaloric substitution of menhaden fish oil for lard affects coronary artery atherosclerosis. The average total plasma cholesterol concentrations during the experimental period were significantly lower for the fish-oil group (231 +/- 37 mg/dl) compared to the lard group (360 +/- 44 mg/dl), but this difference did not become apparent until after 5 months of experimental diet consumption. High density lipoprotein cholesterol concentrations were 30% lower (p less than 0.01) for the fish-oil group also (57 +/- 5 vs. 82 +/- 6 mg/dl). Plasma triglyceride concentrations were low for both groups, but after about 5 months of diet consumption, they were higher for the animals fed fish oil (25 +/- 2 mg/dl) compared to their lard-fed counterparts (15 +/- 1 mg/dl). Coronary artery intimal area (in this case a measure of early atherosclerotic lesion size) was low in all animals but was significantly less (p less than 0.03) for the fish oil vs. lard groups (0.01 +/- 0.002 vs. 0.03 +/- 0.009 mm2). More atherosclerosis was found in other arteries, and a trend was seen of less atherosclerosis in the thoracic aorta and common carotid arteries of the fish-oil group. The size of lesions in the abdominal aorta was similar between diet groups, but microscopic examination of arteries of the lard group revealed relatively more cholesterol monohydrate crystals compared to the arteries of the fish-oil group. Chemical analysis showed that there was less esterified cholesterol (1.46 +/- 0.71 vs. 3.43 +/- 0.74 mg/g, p = 0.04) and free cholesterol (3.7 +/- 2.15 vs. 7.05 +/- 1.68 mg/g, p = 0.08) in the abdominal aortas taken from the animals fed fish oil. There was a significant correlation between low density lipoprotein (LDL) cholesteryl ester (CE) fatty acid ratio (i.e., saturated + monounsaturated/polyunsaturated species) and the amount of esterified (r = 0.59) and free (r = 0.63) cholesterol in the abdominal aortas. Compared to the lard group, animals fed fish oil had significantly lower LDL CE melting temperatures (26 +/- 1 vs. 38 +/- 1 degree C) and significantly smaller LDL particles (2.68 +/- 0.10 vs. 3.25 +/- 0.38 g/mumol). Therefore, the potentially antiatherogenic effects of dietary fish oil include its ability to decrease the concentration, size, CE content, and CE melting temperature of plasma LDL. PMID- 2244859 TI - Vascular responses to endothelin-1 in atherosclerotic primates. AB - Endothelin-1 (ET-1) is a vasoactive peptide that is released by endothelial cells. This study was performed to determine whether vascular responses to ET-1 are altered by atherosclerosis. ET-1 (1 or 10 nmol) was injected intra-arterially into the perfused hind limb of normal cynomolgus monkeys and monkeys fed an atherogenic diet for 19 months. We calculated the resistance of the total limb and large arteries and estimated the resistance of the small vessels. The major finding was that ET-1 had minimal effects on large arteries in normal monkeys but produced pronounced constriction of large arteries in atherosclerotic monkeys. In both groups, ET-1 produced dilatation of small vessels at 1 nmol and constriction at 10 nmol. Indomethacin (6 mg/kg intravenously) did not affect the responses to ET-1 in normal or atherosclerotic monkeys. In summary, the major finding is that the constrictor responses of large arteries to ET-1 are potentiated by atherosclerosis. PMID- 2244860 TI - Characterization in vitro of interaction of human apolipoprotein E-free high density lipoprotein with human hepatocytes. AB - Characterization of the interaction of iodinated apolipoprotein (apo) E-free high density lipoprotein (HDL) with cultured human hepatocytes provides evidence for a saturable, Ca2(+)-independent, high affinity binding site with an apparent km value of 20 micrograms/ml of apolipoprotein. Nitrated HDL and low density lipoprotein (LDL) did not compete for the binding of HDL, in contrast to very low density lipoprotein (VLDL). It is suggested that VLDL competition is exerted by the presence of apo Cs. Degradation of HDL was relatively low and in some cases not detectable. In cases where degradation was found, inhibitors of the lysosomal pathway of protein degradation had no effect, while LDL degradation was inhibited more than 80%. In the presence of 10 microM of monensin, the cell-association of HDL was unaffected, but the degradation was inhibited by 30%. Under similar conditions, LDL association was inhibited by 40% and LDL degradation, by 90%. Incubation of human hepatocytes with fluorescently labeled HDL (Dil-HDL) revealed (in contrast to Dil-LDL) mainly strong membrane-bound fluorescence and hardly any labeling of small intracellular vesicles. It is concluded that human hepatocytes possess a specific high affinity site for human HDL with recognition properties similar to those described earlier on rat hepatocytes. No evidence that the binding of HDL is actively coupled to uptake and lysosomal degradation could be obtained, indicating that binding of LDL and HDL to human hepatocytes is coupled differently to intracellular pathways. PMID- 2244861 TI - Arteriosclerosis: the first 10 years. PMID- 2244862 TI - Are calcium ion antagonists effective anti-atherogenic agents? PMID- 2244863 TI - Calcium antagonists as anti-atherosclerotic agents. PMID- 2244864 TI - Regulation of differentiated properties and proliferation of arterial smooth muscle cells. PMID- 2244865 TI - Rapid and sensitive techniques for identification and analysis of 'reactive centre' mutants of C1-inhibitor proteins contained in type II hereditary angio oedema plasmas. AB - Novel procedures for structural analysis of the 'reactive-centre' residues, particularly the P1 residue, of the dysfunctional C1-inhibitor proteins found in the plasmas of type II hereditary angio-oedema (HAE) patients are described. C1 inhibitor is adsorbed directly from plasma on to Sepharose-anti-(C1 inhibitor) beads. The P1 residue of C1 inhibitor is arginine and hence a potential cleavage site for trypsin. Thus trypsin digestion of the immobilized protein, followed by SDS/PAGE of the released fragments, identifies P1 residue mutations. Pseudomonas aeruginosa elastase digestion of the immobilized protein, followed by purification of the released C-terminal peptide (by h.p.l.c.) and N-terminal sequence analysis defines the new P1 residue (or other mutations in the reactive centre region). The techniques are both rapid and highly sensitive, requiring only 400 microliters of plasma. In addition, they permit accurate assessment of the level of normal (functional) inhibitor in a subclass of type II HAE plasmas, those containing P1-residue mutant proteins. PMID- 2244875 TI - 3-Oxoacyl-(acyl-carrier protein) reductase from avocado (Persea americana) fruit mesocarp. AB - The NADPH-linked 3-oxoacyl-(acyl-carrier protein) (ACP) reductase (EC 1.1.1.100), also known as 'beta-ketoacyl-ACP reductase', has been purified from the mesocarp of mature avocado pears (Persea americana). The enzyme is inactivated by low ionic strength and low temperature. On SDS/PAGE under reducing conditions, purified 3-oxoacyl-ACP reductase migrated as a single polypeptide giving a molecular mass of 28 kDa. Gel-filtration chromatography gave an apparent native molecular mass of 130 kDa, suggesting that the enzyme is tetrameric. The enzyme is inactivated by dilution, but some protection is afforded by the presence of NADPH. Kinetic constants have been determined using synthetic analogues as well as the natural ACP substrate. It exhibits a broad pH optimum around neutrality. Phenylglyoxal inactivates the enzyme, and partial protection is given by 1 mM NADPH. Antibodies have been raised against the protein, which were used to localize it using immunogold electron microscopy. It is localized in plastids. N Terminal amino-acid-sequence analysis was performed on the enzyme, and it shows close structural similarity with cytochrome f. Internal amino-acid-sequence data, derived from tryptic peptides, shows similarity with the putative gene products encoded by the nodG gene from the nitrogen-fixing bacterium Rhizobium meliloti and the gra III act III genes from Streptomyces spp. PMID- 2244878 TI - The reaction of nitrite with the haemocyanin of the Roman snail (Helix pomatia). AB - The reaction of nitrite at pH 5.0-7.0 with the deoxyhaemocyanin of a mollusc, the Roman snail (Helix pomatia), yielded nitrosylhaemocyanin (CuIA.NO+ CuIIB), in contrast with the formation of methaemocyanin with the deoxyhaemocyanin of the crustacean Astacus leptodactylus (mud crayfish). With Helix haemocyanin 1 NO was thereby liberated per active site, as shown by m.s., as against 2 NO with Astacus haemocyanin. Helix nitrosylhaemocyanin was characterized in c.d. by the negative extremum at 336 nm (CuIA.NO+) and by the mononuclear e.p.r. signal at g = 2 (CuIIB). Binuclear e.p.r. signals have been observed after the addition of nitrite to methaemocyanins. With Astacus methaemocyanin, no further reaction occurred, whereas with Helix methaemocyanin the mononuclear e.p.r. signal, characteristic for nitrosylhaemocyanin gradually appeared. This formation of Helix nitrosylhaemocyanin implicates the binding, most likely on CuIIA, of a second nitrite besides a bridging nitrite, so that a dismutation into NO and NO2 can occur there. A further dismutation of NO2 yields nitrite and nitrate. The formation of the latter was demonstrated by Raman spectrometry. The reaction rate of Helix methaemocyanin with nitrite decreased with increasing pH according to the Henderson-Hasselbalch equation with a pKa value of 6.77, attributed to a mu aquo bridging ligand, which can be exchanged for nitrite, in equilibrium with a mu-hydroxo ligand which cannot. These data also favour the formulation of the final reaction product as nitrosylhaemocyanin instead of semi-methaemocyanin, with or without bound nitrite. PMID- 2244874 TI - pH gradient as an additional driving force in the renal re-absorption of phosphate. AB - The effects of the Na+ gradient and pH on phosphate uptake were studied in brush border membrane vesicles isolated from rat kidney cortex. The initial rates of Na(+)-dependent phosphate uptake were measured at pH 6.5, 7.5 and 8.5 in the presence of sodium gluconate. At a constant total phosphate concentration, the transport values at pH 7.5 and 8.5 were similar, but at pH 6.5 the influx was 31% of that at pH 7.5. However, when the concentration of bivalent phosphate was kept constant at all three pH values, the effect of pH was less pronounced; at pH 6.5, phosphate influx was 73% of that measured at pH 7.5. The Na(+)-dependent phosphate uptake was also influenced by a transmembrane pH difference; an outwardly directed H+ gradient stimulated the uptake by 48%, whereas an inwardly directed H+ gradient inhibited the uptake by 15%. Phosphate on the trans (intravesicular) side stimulated the Na(+)-gradient-dependent phosphate transport by 59%, 93% and 49%, and the Na(+)-gradient-independent phosphate transport by 240%, 280% and 244%, at pH 6.5, 7.5 and 8.5 respectively. However, in both cases, at pH 6.5 the maximal stimulation was seen only when the concentration of bivalent trans phosphate was the same as at pH 7.5. In the absence of a Na+ gradient, but in the presence of Na+, an outwardly directed H+ gradient provided the driving force for the transient hyperaccumulation of phosphate. The rate of uptake was dependent on the magnitude of the H+ gradient. These results indicate that: (1) the bivalent form of phosphate is the form of phosphate recognized by the carrier on both sides of the membrane; (2) protons are both activators and allosteric modulators of the phosphate carrier; (3) the combined action of both the Na+ (out/in) and H+ (in/out) gradients on the phosphate carrier contribute to regulate efficiently the re-absorption of phosphate. PMID- 2244867 TI - Insulin and tri-iodothyronine induce glucokinase mRNA in primary cultures of neonatal rat hepatocytes. AB - Glucokinase (EC 2.7.1.2) first appears in the liver of the rat 2 weeks after birth and increases after weaning on to a high-carbohydrate diet. We investigated the hormonal regulation of glucokinase (GK) mRNA in primary cultures of hepatocytes from 10-12-day-old suckling rats. GK mRNA was undetectable in such cells after 48 h of culture in serum-free medium devoid of hormones. Addition of insulin or tri-iodothyronine (T3) to the medium resulted in induction of GK mRNA. The effects of insulin and T3 were dose-dependent and additive. Dexamethasone alone did not induce GK mRNA, but enhanced the response to insulin and decreased the response to T3. Induction of GK mRNA by insulin was not affected when the medium glucose concentration was varied between 5 and 15 mM, nor when culture was conducted in glucose-free medium supplemented with lactate and pyruvate or galactose. The time course of initial accumulation of GK mRNA in response to insulin was characterized by a lag of 12 h and an induction plateau reached after 36 h. If hepatocytes were then withdrawn from insulin for 24 h and subsequently subjected to a secondary stimulation by insulin, GK mRNA re-accumulated with much faster kinetics and reached the fully induced level within 8 h. Both primary and secondary responses to insulin were abolished by actinomycin D. These results provide insight into the role of hormonal stimuli in the ontogenic development of hepatic glucokinase. PMID- 2244872 TI - Molecular cloning of the mammalian fatty acid synthase gene and identification of the promoter region. AB - Rat genomic clones encompassing the entire fatty acid synthase gene have been isolated and characterized. The gene is present in a single copy of approx. 20 kb. Genomic DNA sequencing, direct RNA sequencing and S1 nuclease analysis showed that transcription is initiated primarily 1274 nucleotides upstream from the translation start site and that the 87-nucleotide-long 5'-untranslated mRNA sequence is the same in liver, lung and mammary gland. The 5'-flanking region and first intron contain several sequence elements which may be involved in the transcriptional regulation of this gene. PMID- 2244876 TI - Effect of sodium chloride concentration on fluid-phase assembly and stability of the C3 convertase of the classical pathway of the complement system. AB - The assembly of the classical-pathway C3 convertase from C4 and I2-treated C2 by the action of C1s is an Mg2(+)-dependent reaction. The Mg2+ concentration necessary for the assembly of C3 convertase in the fluid phase was found to be dependent on NaCl concentration. In the absence of NaCl more than 5 mM-MgCl2 was found to be required, whereas 0.5 mM-MgCl2 was adequate for the assembly of C3 convertase in the presence of 150 mM-NaCl. The C3 convertase assembled in a low ionic-strength buffer was extremely labile compared with that assembled in buffer of physiological ionic strength, and the stability of C3 convertase was improved with the increase in NaCl concentration. It was found that the stabilizing effect of NaCl on C3 convertase was due to inhibition of the dissociating activity of C2b, which was formed during the assembly of C3 convertase. In addition to the dissociation-accelerating effect, C2b inhibited the assembly of C3 convertase in low-ionic-strength buffer, and this effect also was diminished with increase in NaCl concentration. An increase in NaCl concentration to more than 200 mM resulted in a decrease in the assembly of C3 convertase. This effect was not due to the lability of the assembled C3 convertase but due rather to the inhibition of C2 cleavage by C1s. Purified C3 convertase itself is stable in dilute medium or high-ionic-strength medium such as 500 mM-NaCl, suggesting that the interactions between C4b and C2a are hydrophobic. In these respects C2b seemed to be functionally similar to C4bp, but C2b failed to act as a cofactor for the Factor I-catalysed C4b cleavage. PMID- 2244879 TI - Inositol phosphate release and steroidogenesis in rat adrenal glomerulosa cells. Comparison of the effects of endothelin, angiotensin II and vasopressin. AB - Endothelin has steroidogenic activity in adrenal glomerulosa cells, as do two other vasoconstrictor peptides, angiotensin II and vasopressin. The steroidogenic activities of angiotensin II and vasopressin are probably mediated via the phosphatidylinositol-turnover pathway and associated changes in cytosolic Ca2+ concentration. Endothelin caused a steroidogenic response, which was small compared with that to angiotensin II and quantitatively similar to the vasopressin response. Cytosolic free Ca2+ responses were similarly higher to angiotensin II than to either of the other two peptides. However, total inositol phosphate responses to endothelin and angiotensin II were similar when these were measured over 20 min, and were quantitatively greater than the vasopressin response. A detailed study has been made of the phosphatidylinositol-turnover response to endothelin in comparison with responses to angiotensin II and vasopressin. Each of the three peptides produced a rapid and transient rise in Ins(1,4,5)P3 (max. 5-15 s), followed by a slow sustained rise. Ins(1,4,5)P3 was metabolized by both dephosphorylation and phosphorylation pathways, but the relative importance of the two metabolic pathways was different under stimulation by each of the three peptides. These findings show that adrenal glomerulosa cells can distinguish between the stimulation of phosphatidylinositol turnover by three different effectors. These differences in the pathway may be associated with the observed different steroidogenic and Ca2+ responses to the three peptides. PMID- 2244880 TI - A novel neutrophil chemoattractant generated during an inflammatory reaction in the rabbit peritoneal cavity in vivo. Purification, partial amino acid sequence and structural relationship to interleukin 8. AB - An inflammatory reaction was induced in vivo by injection of zymosan into the peritoneal cavity of the rabbit. The inflammatory exudate was found to contain oedema-inducing and neutrophil chemoattractant activity when assayed in rabbit skin in vivo, using 125I-albumin and 111In-neutrophils. This activity was additional to that of complement fragment C5a, which was removed by an affinity gel. Two chemoattractants were isolated by cation-exchange, gel-filtration and reversed-phase h.p.l.c. One of these, which ran as a single band of 6-8 kDa on SDS/PAGE, was subjected to N-terminal sequence analysis without reduction and alkylation of cysteine residues. Positive identification of 28 of the first 31 amino acids revealed a rabbit homologue of interleukin-8 (75% sequence identity with human interleukin-8). The demonstration of interleukin-8 as a major neutrophil chemoattractant in an inflammatory reaction in vivo provides the basis for further investigations into the role of this cytokine in the inflammatory process. PMID- 2244886 TI - Identification of a protein kinase C activating factor from murine erythroleukemia cells: characterization of the activation kinetics. AB - A protein kinase C (PKC) activating factor (AF) has been identified in the extracellular medium of V3.17 vincristine resistant murine erythroleukemia (MEL) cells clone. The factor is a protein that stimulates the activity of PKC alpha and beta isozymes isolated from MEL cells, rat and mouse brain approximately 2 to 2.5 fold over the Vmax, respectively. AF promotes an identical activation in the presence of all the effectors but also when the amount of Ca2+ is reduced to microM concentration and in the absence of diacylglycerol (DAG). The factor shows a greater activating efficiency with PKC beta isozymes. AF binds to PKC presumably at the DAG binding site as suggested by the competition between phorbol dibutyrate and AF for binding to the kinase. Moreover, AF promotes the selective binding of PKC beta to natural or artificial membranes in the presence of microM concentrations of Ca2+. Altogether these results suggest the presence in MEL cells of a protein factor that can promote association of PKC to the membranes together with activation of the kinase, without the requirement for DAG formation. This could be visualized as a new mechanism for prolonged and selective activation of PKC. PMID- 2244883 TI - Computer simulation of a cytosolic calcium oscillator. AB - A new interpretation of existing data permits us to define a model capable of accounting for agonist-induced Ca2+ oscillations in the cytosol of electrically non-excitable cells. The model only requires one Ca2+ store, which contains Ca2+ channels controlled by inositol 1,4,5-trisphosphate and Ca2+. Computer simulations may generate different experimentally observed patterns of Ca2+ oscillations. PMID- 2244871 TI - Expression of endoplasmic-reticulum Ca2(+)-pump isoforms and of phospholamban in pig smooth-muscle tissues. AB - The expression of the gene 2 sarcoplasmic/endoplasmic-reticulum Ca2(+)-pump isoforms (SERCA2a and SERCA2b) and of phospholamban was studied in pig smooth muscle of the stomach, longitudinal ileum, pulmonary artery and aorta. mRNA levels were determined using an RNAase protection assay. The SERCA2 isoforms and phospholamban were tested on Western blots with a panel of antibodies, some of which were isoform-specific. The pig smooth-muscle tissues all contained comparable SERCA2 mRNA levels, but these levels were 10-20-fold lower than SERCA2 mRNA levels in cardiac muscle. Of the SERCA2 mRNAs in smooth muscle, 72-81% encoded the non-muscle isoform (SERCA2b), and Western blot analysis with isoform specific antibodies confirmed that the SERCA2b isoform is the predominant endoplasmic-reticulum Ca2(+)-pump in smooth muscle. In contrast with SERCA2 mRNA levels, phospholamban mRNA levels varied by 12-fold between the different pig smooth-muscle tissues, with low and very low levels in the pig pulmonary artery and the pig aorta respectively. The differential expression of phospholamban was also confirmed on Western blots. The finding that the phospholamban content varied between the different smooth-muscle tissues whereas the SERCA2 expression remained rather constant indicates that, in pig smooth muscle, the expression of phospholamban is not coupled with that of SERCA2. PMID- 2244885 TI - Molecular oxygen as electron acceptor in the NADH-nitrate reductase system. AB - This paper describes first experimental evidence that dissolved molecular oxygen acts as an electron acceptor in the NADH-nitrate reductase system. The molecular mechanism and possible physiological implications on the induction mechanism of nitrate reductase by nitrate ion are discussed. PMID- 2244884 TI - Rubredoxin from Clostridium thermosaccharolyticum. Amino acid sequence, mass spectrometric and preliminary crystallographic data. AB - Rubredoxin isolated from the thermophilic bacterium Clostridium thermosaccharolyticum has been sequenced and crystallized. The 52-residue sequence is similar to those of rubredoxins occurring in other anaerobic bacteria, but displays some unique features, including a tryptophan residue in position 4, two consecutive proline residues in positions 25 and 26, and an aspartic acid residue in position 41. The molecular mass (5988 Da) of the native rubredoxin has been measured by electrospray-ionization m.s., thus establishing the applicability of the technique to this type of iron-sulphur protein. C. thermosaccharolyticum rubredoxin crystallizes as dark-red elongated prisms with a flat diamond cross-section. The X-ray diffraction shows symmetry consistent with space group P2(1)2(1)2(1). Cell parameters are: a = 2.73 nm, b = 2.98 nm, c = 6.49 nm. PMID- 2244870 TI - Measurement of matrix free Mg2+ concentration in rat heart mitochondria by using entrapped fluorescent probes. AB - 1. The concentration of free Mg2+ ([Mg2+]m) within the matrix of isolated rat heart mitochondria was measured after loading of the mitochondria with the fluorescent Mg2+ indicators mag-indo-1 and mag-fura-2. No detectable change in total mitochondrial magnesium content occurred during loading with the indicators. Apparent Kd values for Mg2+ of 3.7 mM and 2.3 mM were obtained for mag-indo-1 and mag-fura-2 respectively within mitochondria permeabilized to bivalent cations with ionomycin and the uncoupler carbonyl cyanide p trifluoromethoxyphenylhydrazone. These values are 2.7- and 1.8-fold greater respectively than those obtained for the free acid forms of the dyes in incubation medium. 2. Based on the above Kd values, mitochondrial matrix Mg2+ concentrations were found to lie in the range 0.8-1.5 mM in the absence, or immediately after the addition, of a respiratory substrate. 3. Incubation of mitochondria in the presence of respiratory substrate, but in the absence of external Mg2+, led to a time-dependent decline in [Mg2+]m to about half the initial values after 5 min. This was accompanied by a fall in the total mitochondrial magnesium content from 12.7 to 7.0 nmol/mg of protein. 4. ADP (0.5 mM), ATP (0.5 mM) or 10 mM-NaCl had no significant effect on the fall in [Mg2+], whereas 1 microM-nigericin blocked, and 0.3 microM-valinomycin accelerated, the fall. 5. External Mg2+ concentrations above 1 mM progressively inhibited and reversed the decline in free and total mitochondrial Mg2+. PMID- 2244887 TI - Enzyme induction in recovering dauer larvae of the nematode Caenorhabditis elegans in response to increasing concentrations of food source in the recovery medium. AB - Exposure of recovering dauer larvae of Caenorhabditis elegans to increasing concentrations of Escherichia coli in the recovery medium produced dramatic increases in the enzymes of intermediary metabolism. There was no significant difference between the rates of development of recovering dauer larvae grown on different concentrations of E. coli. When the activity of several key enzymes was assayed after 12, 22 and 32 hours of recovery in 0.5% w/v E. coli it was found that the activities recorded never reached levels observed at 12 hours for larvae grown on the optimum concentration of E. coli. These results imply that enzymes of intermediary metabolism in the nematode C. elegans are capable of being induced in response to changes in nutrient intake, as previously described for mammals and microorganisms. PMID- 2244869 TI - Changes in inositol lipids and phosphates after stimulation of the MAS transfected NG115-401L-C3 cell line by mitogenic and non-mitogenic stimuli. AB - A neuronal cell line (NG115-401L-C3) was stimulated by mitogenic (angiotensin) and non-mitogenic (bradykinin) peptides and examined for the time course of changes in the levels of radiolabelled inositol phosphates and phospholipids. Both peptides stimulated the time-dependent production of Ins(1,4,5)P3 and related metabolites. Bradykinin caused a much larger increase in Ins(1,4,5)P3 than did angiotensin. However, both peptides stimulated similar rises in the levels of Ins(1,3,4)P3 and InsP4. Bradykinin, but not angiotensin, caused a rapid (within 2 s) fall in the levels of PtdIns(4,5)P2 and PtdIns(4)P. Serum pretreatment of the cells caused a 2-3-fold potentiation of both the responses to bradykinin and angiotensin. Although significant levels of PtdIns(3)P were detected in resting cells, neither mitogenic (angiotensin, insulin-like growth factor I, transforming growth factor beta) nor non-mitogenic (bradykinin, nerve growth factor, interleukin-1) receptor activation changed its levels, arguing against regulation of either PtdIns 3-kinase or PtdIns(3)P phosphatase. We conclude that, as judged by the levels of its product. PtdIns(3)P, the enzyme PtdIns 3-kinase is not activated. This questions the significance of this activity in the receptor-mediated initiation of DNA synthesis. PMID- 2244889 TI - Interleukin-4 as a potent inhibitor of bone resorption. AB - A possible role of interleukin-4 (IL-4) in the regulation of bone turnover was assessed by employing a 45Ca prelabeled-fetal mouse long bone culture system. IL 4 inhibited the bone resorption stimulated by parathyroid hormone (PTH), PTH related protein (PTHrP), 1 alpha, 25, dihydroxy-vitamin D3 [1 alpha, 25 (OH)2 D3], interleukin-1 alpha and - 1 beta (IL-1 alpha, IL-1 beta) and prostaglandin E2 (PGE2). Anti-IL-4 on monoclonal antibody abolished the inhibitory effect of IL 4 on the bone resorption. These results suggest that IL-4 may play an important role on the inhibitory regulation of bone resorption. PMID- 2244892 TI - Role of protein kinase C in the inhibition by fibroblast growth factor of apoptosis in serum-depleted endothelial cells. AB - Apoptosis in vascular endothelial cells is suppressed by fibroblast growth factor (FGF)1. In order to investigate the signal transduction system that regulates endothelial apoptosis, we studied the effects of several mitogenic factors. Apoptosis occurred in human vascular endothelial cells under serum-free conditions, and FGF inhibited apoptosis without a requirement of any cooperative factors, as distinct from the mitogenic response. Other mitogenic agents, such as epidermal growth factor, transferrin, transforming growth factor beta, and interleukin 1 etc., with the exception of dexamethasone, had no such inhibitory effects. The effect of FGF was mimicked by a phorbol ester and was prevented by an inhibitor of protein kinase C. The results suggest that the FGF and protein kinase C are important in endothelial apoptosis. PMID- 2244873 TI - Evidence for a non-myristoylated pool of the 80 kDa protein kinase C substrate of rat brain. AB - A protein of 80 kDa apparent molecular mass was found to be specifically myristolylated in rat brain cytosols derived from either whole brain or synaptosomes. The attachment of the fatty acid took place in the absence of protein synthesis, since the cytosols did not incorporate [14C]lysine into protein, nor did cycloheximide affect the incorporation of the myristic acid into the protein. The fatty acid was incorporated into the protein via an acid labile/alkali-resistant band, and Pronase digestion of the labelled protein showed that the lipid was covalently linked to a glycine residue. Together, these data suggested that the myristic acid was amide-linked to the N-terminal residue of the protein. The protein was identified as one of the major protein kinase C substrates, the MARCKS (myristoylated alanine-rich C kinase substrate) protein, by showing that Ca2+ stimulated its phosphorylation, by its heat stability and by immune precipitation (using an antiserum to the MARCKS protein). Incorporation of myristic acid into intact protein continued for up to 12 h, despite the fact that over this period some degradation of the protein could be demonstrated. In pulse chase experiments, the pattern of loss of the incorporated fatty acid was similar to that of the protein itself, and therefore the loss of radioactivity probably reflects protein degradation rather than specific de-acylation of the protein. Together, these results suggest that there is a pool of unacylated MARCKS protein in the rat brain. PMID- 2244881 TI - Apolipoprotein D is the major protein component in cyst fluid from women with human breast gross cystic disease. AB - GCDFP(gross-cystic-disease-fluid protein)-24, a progesterone-binding protein present in large amounts in cyst fluid from human breast gross cystic disease, was purified in a one-step procedure by size-exclusion h.p.l.c. Peptide fragments obtained by trypsin digestion of the intact protein were purified by reverse phase h.p.l.c. and analysed for their amino acid composition and subjected to automated Edman degradation. A search of the National Biomedical Research Foundation Data Bank revealed that all the sequenced tryptic peptides from protein GCDFP-24 matched perfectly with regions present in the amino acid sequence determined for human apolipoprotein D. Additional data on N-terminal sequence of the unblocked proteins, carbohydrate-attachment sites, amino acid composition and molecular-mass estimations supported the identity between both molecules. On the basis of this identity a possible role of apolipoprotein D in progesterone transport is proposed. PMID- 2244882 TI - Interleukin-1 beta prevents the stimulatory effect of transforming growth factor beta on collagen gene expression in human skin fibroblasts. AB - Transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-beta 1 or TGF-beta 2 increases pro alpha 1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1 beta (IL-1 beta) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1 beta (0.01-1.0 unit/ml) slightly increases pro alpha 1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1 beta prevents the stimulatory effect of TGFs-beta on collagen synthesis in human skin fibroblasts. An IL-1 beta concentration of 1 unit/ml is enough to keep pro alpha 1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-beta 1. Thus the results indicate that IL-1 beta inhibits collagen synthesis in cells activated by TGFs-beta, whereas it does not significantly change or might even stimulate collagen gene expression in non activated cells. PMID- 2244868 TI - Differential control of glycogenolysis and flow by arterial and portal acetylcholine in perfused rat liver. AB - The effects of acetylcholine on glucose and lactate balance and on perfusion flow were studied in isolated rat livers perfused simultaneously via the hepatic artery (100 mmHg, 25-35% of flow) and the portal vein (10 mmHg, 75-65% of flow) with a Krebs-Henseleit bicarbonate buffer containing 5 mM-glucose, 2 mM-lactate and 0.2 mM-pyruvate. Arterial acetylcholine (10 microM sinusoidal concentration) caused an increase in glucose and lactate output and a slight decrease in arterial and portal flow. These effects were accompanied by an output of noradrenaline and adrenaline into the hepatic vein. Portal acetylcholine elicited only minor increases in glucose and lactate output, a slight decrease in portal flow and a small increase in arterial flow, and no noradrenaline and adrenaline release. The metabolic and haemodynamic effects of arterial acetylcholine and the output of noradrenaline and adrenaline were strongly inhibited by the muscarinic antagonist atropine (10 microM). The acetylcholine-dependent alterations of metabolism and the output of noradrenaline were not influenced by the alpha 1 blocker prazosin (5 microM), whereas the output of adrenaline was increased. The acetylcholine-dependent metabolic alterations were not inhibited by the beta 2 antagonist butoxamine (10 microM), although the overflow of noradrenaline was nearly completely blocked and the output of adrenaline was slightly decreased. These results allow the conclusion that arterial, but not portal, acetylcholine caused sympathomimetic metabolic effects, without noradrenaline or adrenaline being involved in signal transduction. PMID- 2244877 TI - Regulation of hepatic synthesis and secretion of cholesterol and glycerolipids in animals maintained in different nutritional states. AB - The distribution of newly synthesized and exogenous fatty acids and of newly synthesized cholesterol between cellular and very-low-density lipoprotein (VLDL) lipids was studied in hepatocytes derived from animals fed on a normal diet or on diets supplemented with polyunsaturated fat or sucrose. Phospholipid synthesis from either exogenous or endogenous (biosynthetic) fatty acids was unaffected by nutritional state. Cholesterol synthesis was decreased in the fat-fed animals, but sucrose feeding had no significant effect. In all nutritional states, newly synthesized rather than exogenous fatty acids were better substrates for phospholipid synthesis. In all groups, compared with newly synthesized triacylglycerol, smaller proportions of newly synthesized phospholipid and cholesterol were secreted as VLDLs. This was confirmed in intact animals by using Triton WR-1339. Newly synthesized phospholipid formed a greater proportion of the VLDL glycerolipid in the fat-fed than in the normal or sucrose-fed animals. In all groups, phospholipids labelled from endogenous fatty acids were secreted in preference to those labelled from exogenous fatty acids. PMID- 2244866 TI - Stimulation of apolipoprotein secretion in very-low-density and high-density lipoproteins from cultured rat hepatocytes by dexamethasone. AB - The effects of dexamethasone (a synthetic glucocorticoid) and insulin on the secretion of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were investigated. Rat hepatocytes in monolayer culture were preincubated for 15 h in the presence or absence of combinations of 100 nM-dexamethasone and 2 nM-, 10 nM- or 50 nM-insulin. Dexamethasone increased [3H]oleate incorporation into secreted triacylglycerol by 2.7-fold and the mass of triacylglycerol secreted by 1.5-fold. Insulin alone decreased these parameters and antagonized the effect of dexamethasone. Dexamethasone increased the secretion of [3H]leucine in apolipoprotein (apo) E, and in the large (BH) and small (BI) forms of apo B in VLDL by about 7.1-, 3.6- and 4.0-fold respectively. Insulin alone decreased the secretion of these 3H-labelled apolipoproteins in VLDL. However, 2 nM-insulin with dexamethasone increased the secretion of 3H-labelled apo BH and apo BL by a further 0.8- and 3.2-fold respectively; 50 nM-insulin decreased the secretions of apo E, apo BH and apo BL in VLDL. Similar effects for dexamethasone or insulin alone were also obtained for the masses of apo E and apo BL + H secreted in VLDL. Albumin secretion was not significantly altered by either dexamethasone or insulin alone, but in combination they stimulated by 2.1-2.6-fold. Insulin or dexamethasone alone had little effect on the secretion of apolipoproteins in the HDL fraction. However, dexamethasone plus 2 nM-insulin increased the incorporation of [3H]leucine into apo AI, apo AH plus apo C, apo AIV and apo E of HDL by about 1.8-, 1.6-, 1.7- and 2.0-fold respectively. The apo E in the bottom fraction represented about 69% of the total 3H-labelled apo E secreted. The responses in the total secretion of apo E from the hepatocytes resembled those seen in HDL. The interactions of insulin and dexamethasone are discussed in relation to the general regulation of lipoprotein metabolism, the development of hyperlipidaemias and the predisposition to premature atherosclerosis. PMID- 2244890 TI - Cloning and sequencing of human LH/hCG receptor cDNA. AB - We have isolated and sequenced a cDNA encoding the human luteinizing hormone- choriogonadotropin (LH/hCG) receptor. The deduced amino acid sequence (699 residues) containing seven putative transmembrane segments displays sequence similarity to G protein-coupled receptors. The receptor consists of 335 residue extracellular domain which contains six N-linked glycosylation sites. While the protein is 85 and 87% identical overall with the previously cloned rat and porcine LH/hCG receptor respectively, the most highly conserved regions are the putative transmembrane segments (91 and 94% similarity, respectively). PMID- 2244891 TI - 7-Substituted pterins: formation during phenylalanine hydroxylation in the absence of dehydratase. AB - Previously we described a new form of human hyperphenylalaninemia characterized by the formation of 7-substituted pterins. We present evidence strongly suggesting that the 7-substituted pterins are formed by rearrangement of 6 substituted pterins. This rearrangement occurs during the phenylalanine hydroxylase reaction cycle which normally involves the enzymes phenylalanine hydroxylase, pterin-4a-OH-dehydratase, and q-dihydropterin reductase, specifically in the absence of dehydratase activity. We conclude that formation of 7-substituted pterins in humans is a consequence of an absence of dehydratase activity, which might result from a genetic defect. A chemical mechanism for this rearrangement is presented. Our results also suggest that tetrahydroneopterin can be a cofactor for the phenylalanine hydroxylase system in vivo. PMID- 2244894 TI - Heterogeneity in chemotaxis of neutrophils with different densities. AB - We investigated N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP)-induced chemotaxis of neutrophils with different densities. FMLP-induced (10(-8)M) chemotaxis of neutrophils with lower density were significantly reduced when compared to neutrophils with higher density (p less than 0.05). These findings imply a relationship between the neutrophil density and chemotaxis. PMID- 2244893 TI - Hydrocortisone-induced enhancement of expression and changes in methylation of pepsinogen genes in stomach mucosa of the developing rat. AB - Administration of hydrocortisone to infant rats caused a precocious increase in levels of mucosal pepsinogen and its mRNA together with morphological maturation of pepsinogen-producing cells. The increase in levels of pepsinogen mRNA was induced rapidly and was associated with increase in levels of its precursors, suggesting transcriptional regulation of pepsinogen genes by hydrocortisone. Methylation analysis with the methylation-sensitive restriction enzymes, HpaII and HhaI, revealed that hydrocortisone also induced sequential demethylation changes of CCGG and GCGC sites in and around pepsinogen genes. Most of these changes occurred after increases in transcription of the genes and did not appear to play a causal role in gene activation. Superficially, the observed demethylations corresponded to the sequential processes of morphological maturation of pepsinogen-producing cells. Thus, these changes in methylation are probably linked to hydrocortisone-induced differentiation of pepsinogen-producing cells and may reflect the mechanism in vivo for the maturation of pepsinogen genes. PMID- 2244888 TI - Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblasts. AB - We have investigated the effects of recombinant human tumor necrosis factor (TNF)/cachectin on the cellular binding of human low density lipoprotein (LDL) to human skin fibroblasts. When recombinant TNF was added to cultured cells, LDL binding doubled after 24 h of incubation. The effect of TNF was dose-dependent and its maximal effect was observed at concentrations of 1-10 ng/ml. TNF also stimulated the growth of human skin fibroblasts 1.6-fold. These results indicate that TNF increases LDL-receptor activity, which might be related to its stimulatory effect on cell growth. PMID- 2244895 TI - Exclusion of an exon in monocyte alpha-1-antitrypsin mRNA after stimulation of U937 cells by interleukin-6. AB - Monocytes potentially express two mRNA species by alternative splicing of exons at the 5' end of the gene. During inflammation the plasma concentration of AAT can increase about three-fold. In a myelomonocytic cell line (U937), under basal conditions, two AAT mRNA species are produced. After stimulation by interleukin-6 (IL-6) one mRNA species is produced resulting from the exclusion of the second monocyte exon. These findings demonstrate a novel way in which the expression of mRNA can be modified in a single cell type. PMID- 2244896 TI - The transition of the higher-order structure of rat liver chromatin takes place at about 85% neutralization of DNA charges. AB - The salt dependence of the stoichiometry in the binding of linker histone to rat liver chromatin was analysed. It was found that the transition of the higher order structure of chromatin (between folded and unfolded) takes place at the point of approximately 85% neutralization of DNA charges in chromatin, as in a related process in the B-Z transition of double-helical DNA. PMID- 2244897 TI - Reversal of endotoxin-mediated shock by NG-methyl-L-arginine, an inhibitor of nitric oxide synthesis. AB - Septic shock is a life-threatening condition that results from exposure to bacterial endotoxin. It is manifested by cardiovascular collapse and mediated by the release of cytokines such as tumor necrosis factor. Some of these cytokines cause the release of vasoactive substances. In the present study, administration of 40 microgram/kg of bacterial endotoxin to dogs caused a 33% decrease in peripheral vascular resistance and a 54% fall in mean arterial blood pressure within 30 to 90 minutes. Vascular resistance and systemic arterial pressure returned to normal within 1.5 minutes after intravenous administration of NG methyl-L-arginine (20 mg/kg), a potent and selective inhibitor of nitric oxide synthesis. L-Arginine reversed the effect of L-NMA and restored the endotoxin induced hypotension. Although NG-methyl-L-arginine injection increased blood pressure in control dogs, the hypertensive effect was much greater in endotoxemic dogs (24.8 +/- 2.7 mmHg vs 47.8 +/- 6.8 mmHg, p = 0.01, n = 4). NG-Methyl-L arginine caused only a modest increase in blood pressure in dogs made hypotensive by continuous intravenous infusion of nitroglycerin (17.1 +/- 5.0 mm Hg, n = 3). These findings suggest that nitric oxide overproduction is an important contributor to endotoxic shock. Moreover, our findings demonstrate for the first time, the utility of nitric oxide synthesis inhibitors in endotoxic shock and suggest that such inhibitors may be of therapeutic value in the treatment of septic shock. PMID- 2244898 TI - Amino acid sequence of human protein Z, a vitamin K-dependent plasma glycoprotein. AB - Protein Z is a vitamin K-dependent glycoprotein isolated and characterized from human and bovine plasma. A cDNA coding for human protein Z has been obtained by the isolation of phage clones from a liver cDNA library and in vitro amplification of two other liver libraries. Protein Z is synthesized with a prepro-leader sequence of 40 amino acids. The mature protein is composed of 360 residues including a Gla domain of 13 carboxyglutamic acid residues, two epidermal growth factor domains, and a carboxyl terminal region which is highly homologous to the catalytic domain of serine proteases. Human protein Z, however, contains an Asp instead of Ser and a Lys instead of His in the catalytic triad of the active site. PMID- 2244899 TI - Multiple mRNAs encoding human calmodulin. AB - In humans, as in rats, four distinct molecular weight species of mRNA encoding calmodulin exist, i.e. 1.6 Kb for L, 1.4 Kb for T2 and 2.5 and 1.0 Kb for T1. They result from the expression of three genes. Each of these mRNAs codes for a calmodulin identical in amino acid sequence. The 5' and 3' untranslated regions of these mRNAs, however, differ extensively, and oligonucleotide probes specific to these regions were used in this study. The poly A+ mRNA was isolated from human erythroleukemia cells and also from human B cells infected with EBV. PMID- 2244900 TI - Modulation of resting membrane potential of human and rat hepatocytes by sex steroids. AB - The effect of sex steroids on the regulation of hepatocyte resting membrane potential (Em) was investigated. In adult rat liver snips, Em was significantly lower in males than females. In prepubertal animals no sex related difference was observed and the Em was comparable to that of adult females. Exposure of the human liver cell line, HepG2 cells, to 10 microM testosterone resulted in a significant hyperpolarization. These data indicate that the more negative Em found in male animals is specifically due to the influence of testosterone. In addition, they also suggest that sex hormone regulation of Em is maintained by HepG2 cells. This cell line may prove to be a good model for the study of liver cell function. PMID- 2244901 TI - Galactosialidosis: simultaneous deficiency of esterase, carboxy-terminal deamidase and acid carboxypeptidase activities. AB - Esterase and deamidase activities at pH 7.0 and carboxypeptidase activity at pH 5.7 were markedly low or deficient in seven galactosialidosis fibroblast strains with deficient activity of "protective protein" for lysosomal beta-galactosidase and neuraminidase. No simultaneous deficiency of these three enzyme activities was observed in other lysosomal disease fibroblasts examined in this study. This result strongly suggests that "protective protein" is identical with a multifunctional protein with esterase/deamidase/carboxypeptidase activities and its mutation in galactosialidosis results in deficiency of these three enzyme activities. PMID- 2244902 TI - Angiotensin II can regulate gene expression by the AP-1 binding sequence via a protein kinase C-dependent pathway. AB - An expression vector containing three copies of the AP-1 binding element (TRE) upstream of a thymidine kinase promotor which controlled the expression of the chloramphenicol acetyl transferase (CAT) gene was transiently transfected into vascular smooth muscle (VSM) cells and a human hepatocarcinoma cell line, Hep G2. Twelve hours of angiotensin (Ang) II exposure stimulated significantly CAT expression by 3.4 fold and 2.7 fold in Hep G2 and VSM cells, respectively. AngII had no effect on CAT expression of a control vector. This AngII-induced stimulation was attenuated significantly by an AngII receptor antagonist, Sar1 Ile8 AngII, and abolished completely by a PKC inhibitor, staurosporine. Our data suggest that the TRE plays a crucial role in AngII-induced gene expression that is mediated by PKC. We concluded that TRE is one of the AngII-responsive elements. PMID- 2244903 TI - [3H]DUP 753, a highly potent and specific radioligand for the angiotensin II-1 receptor subtype. AB - [3H]Dup 753, a nonpeptide angiotensin II (AII) receptor antagonist radioligand, was used to characterize a subtype of AII receptors in rat adrenal cortical microsomes. By Scatchard analysis, a single class of DuP 753 binding sites was found with an affinity of 6.4 nM and a Bmax of 1.3 pmol/mg protein. These sites were saturable and readily reversible. Angiotensin (I, II, III) expressed the same affinities and order of potency for these binding sites as those labeled by [3H]AII for the AII-1 sites. The affinities expressed by nonpeptide AII antagonists were commensurate with their inhibitory potencies on AII-1 receptors. PD123177, an AII-2 specific ligand, and other non-AII peptides showed no inhibitory action. These data together with the differential tissue distribution strongly support our conclusion that [3H]DuP 753 is a potent and highly specific radioligand for the AII-1 receptors. PMID- 2244904 TI - Exudation induces clustering of CR1 receptors at the surface of human polymorphonuclear leukocytes. AB - The complement receptor type 1 (CR1) surface distribution, density and immune adherence efficiency were determined in circulating PMN activated by fMLP, NAP 1/IL-8, TNF, GM-CSF and C5a, or exudate PMN harvested from skin-blisters. These observations were compared with those observed on resting peri-pheral blood PMN. PMN activators known to upregulate CR1 expression did not induce a significant increase in CR1 clustering, or immune adherence efficiency towards opsonized immune complexes. By contrast, increase in CR1 density at the surface of exudated PMN was accompanied by an increased clustering. This clustering was however insufficient to increase the binding efficiency for immune complexes. Eventually, CR1 expression of exudated neutrophil could not be increased further by stimulation with fMLP or PMA. These results indicated that clustering of CR1 on PMN may occur in vivo. Such reaction might determine the phagocytic potential of the cell for opsonized micro-organisms or debris. This clustering could not be attributed to one of the PMN activators tested. PMID- 2244905 TI - Selective synthesis and secretion of a 23 kD protein by neutrophils following stimulation with granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. AB - We tested a wide range of pro-inflammatory cytokines for their capacity to activate protein synthesis in neutrophils as analyzed b y [35S] methionine metabolic labelling experiments. Of all the cytokines tested, only GM-CSF and TNF alpha stimulated significant synthesis and secretion of a 23 kD protein which resolved into two bands on two dimensional gels. Under non-reducing conditions on one dimensional gels, its migration pattern remained the same indicating that the two bands most likely represent isoforms of the same protein. Immunoisolation studies using antibodies directed against size-relevant molecules did not lead to the identification of this molecule. The fact that this 23 kD molecule is induced in a highly specific and selective manner by GM-CSF and TNF alpha indicates that it may play a key role in some of the responses of neutrophils to these two cytokines. Therefore, full characterization of this 23 kD protein could provide important new knowledge on the mechanisms by which these two cytokines exert their biological effects on neutrophils. PMID- 2244906 TI - Comparison of the lectin-like activity of pertussis toxin with two plant lectins that have differential specificities for alpha (2-6) and alpha (2-3)-linked sialic acid. AB - In this report we have compared the lectin-like properties of Pertussis toxin with two plant lectins which are known to possess different specificities towards terminal Neu5Ac Gal linkages on glycoconjugates. The hemagglutinin from elderberry bark (Sambucus nigra) has a binding specificity for terminal Neu5Ac alpha (2-6) Gal sequences and was found to bind a series of glycoconjugates with a similar specificity as Pertussis toxin. The binding specificity of Pertussis toxin was different from that of the leukoagglutinin from the seeds of Maackia amurensis which preferentially binds terminal Neu5Ac alpha (2-3) Gal sequences. These observations confirm the specificity of Pertussis toxin for Neu5Ac alpha (2 6) Gal glycoconjugate sequences. PMID- 2244907 TI - Molecular cloning and expression of human arachidonate 12-lipoxygenase. AB - The cDNA for a 12-lipoxygenase was isolated from cDNA library of human erythroleukemia cells. The cDNA had an open reading frame encoding 663 amino acids with a calculated molecular weight of 75,513. The deduced amino acid sequence of human 12-lipoxygenase exhibited 41.5%, 65.3% and 65.4% identity with human 5-lipoxygenase, human 15-lipoxygenase and porcine 12-lipoxygenase, respectively. Blot hybridization analysis of RNA from human erythroleukemia cells demonstrated a single species (3.1 kb) of mRNA with the cDNA probe for 12 lipoxygenase of these cells, but not with the cDNA for porcine leukocyte enzyme. The cytosol of Escherichia coli transformed with a recombinant pUC19 plasmid oxygenated the position 12 of arachidonic acid. PMID- 2244908 TI - Movement of vesicles in cytoplasmic streaming in plasmodium. AB - The moving velocities of vesicles in the cytoplasmic streaming of a slime mold were measured, in which all of the vesicles passing through a designated window were counted. Vesicles in the streaming are distributed in their moving velocities and the distribution itself varies with time. The mean velocity of vesicles and its standard deviation were found to exhibit a linear relationship, suggesting a possibility that vesicles in the cytoplasm would also be involved in force generation. PMID- 2244909 TI - The regulation of N-acetylglutamate synthetase in rat liver by protein intake. AB - Urea cycle enzymes are subjected to regulation by dietary proteins. We have shown that this is also the case for N-acetylglutamate synthetase (EC 2.3.1.1.) (NAGS). Four different groups (n = 7) of male Wistar rats received either a low protein (8.7%) or a high (32% and 51%) protein diet and a control diet of 17% protein. The NAGS-activity in the liver, assayed after 15 days of feeding the different diets, increased from 25 +/- 7 (controls, 17% protein) to 31 +/- 5 (32% protein) and to 52 +/- 17 (51% protein) nmoles.min-1.g-1 wet weight. It decreased in the group with low protein diet (8.7%) to 5 +/- 3. The ratio of the arginine stimulated to the unstimulated enzyme activity remained constant over the range of protein intake. Similar changes were observed for carbamylphosphate synthetase, ornithine carbamyltransferase and arginase. As it is known for these enzymes adaptive mechanisms in relation to variations in dietary protein consumption also could be demonstrated for the enzyme NAGS. PMID- 2244910 TI - Anti-influenza virus activity of synthetically polymerized phenylpropenoids. AB - Various dehydrogenation polymers (the so-called synthetic lignins) were synthesized from four different phenylpropenoids by endwise and bulk polymerizations and investigated for their anti-influenza virus activity. All of these materials suppressed the plaque formation of influenza virus infecting MDCK cells and the RNA-dependent RNA synthesis as effectively as the high molecular weight lignin-related extract (Fr. VI) of pine cone of Pinus parviflora Sieb. et Zucc. The structural simplicity and higher solubility of the synthesized polymers suggest that they might be regarded as potential candidates for medicinal antiviral resources. PMID- 2244911 TI - Protein kinase C inhibitors block the enhanced expression of intercellular adhesion molecule-1 on endothelial cells activated by interleukin-1, lipopolysaccharide and tumor necrosis factor. AB - Interleukin 1 (IL-1), bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) enhance the adherence properties of endothelial cells (EC) for neutrophils (PMN). This is mediated in part by the up-regulation of Intercellular Adhesion Molecule 1 (ICAM-1) on EC. Phorbol esters, which activate protein kinase c (PKC) and enhance the adherence properties of EC for PMN also up-regulate the ICAM-1 expression on EC. We investigated the effect of PKC inhibitors on ICAM-1 expression of human umbilical vein EC (HUVEC). Staurosporine (STS) and 1-(5 isoquinolinylsulfonyl)-2-methylpiperazine (H-7) prevented inflammatory mediator dependent stimulation of both ICAM-1 expression and PMN adherence by HUVEC (ID50 for STS = 2.7-2.9 microM; for H-7 = 7.6-8.8 microM). Inhibition was dose and time dependent and was not due to HUVEC toxicity. The STS analog K252a and the H-7 analog W-7 were less potent inhibitors of ICAM-1 up-regulation and adherence promotion. Prolonged exposure of HUVEC to phorbol myristate acetate down regulated PKC activity and inhibited subsequent ICAM-1 up-regulation by this agent and by IL-1. We conclude that inflammatory mediator induced stimulation of HUVEC expression of ICAM-1 and promotion of adherence properties are mediated in part by activation of PKC. PMID- 2244912 TI - Desensitization and muscarinic re-sensitization of force and myosin light chain phosphorylation to cytoplasmic Ca2+ in smooth muscle. AB - In alpha-toxin-permeabilized guinea-pig ileum smooth muscle, a step increase in Ca2+ caused a rapid rise in force and myosin light chain (LC20) phosphorylation, followed by their spontaneous decline to a low steady level even though Ca2+ remained constant. Carbachol resensitized the muscles to Ca2+, causing an increase in both the steady state force and LC20 phosphorylation at constant Ca2+. In beta-escin permeabilized preparations, calmodulin and okadaic acid converted the phasic responses to Ca2+ to more tonic ones. We conclude that Ca2(+)-sensitivity of force is modulated through changes in LC20 kinase/phosphatase activity ratio by Ca2+ itself (desensitization) and by agonists (sensitization). PMID- 2244914 TI - The CDC4 gene product is associated with the yeast nuclear skeleton. AB - The CDC4 gene product of Saccharomyces cerevisiae is required at the late G1/S phase boundary of the cell cycle. In an attempt to better understand the function of CDC4, we performed experiments to localize this protein in the yeast cell. Using antisera, directed against a TrpE-CDC4 fusion protein, to analyze immuno blots of different subcellular fractions from yeast, we demonstrated that the CDC4 gene product localizes in the nucleus by two different biochemical preparations of the yeast nucleoskeletal proteins. Immunofluorescence microscopy further confirmed its nuclear localization. These data support a model that includes the CDC4 gene product as a component of the yeast nuclear skeleton. The significance of this association in relationship to the biological role of CDC4 is discussed. PMID- 2244913 TI - Total in vitro maturation of the Saccharomyces cerevisiae a-factor lipopeptide mating pheromone. AB - The a-factor mating pheromone, produced by Saccharomyces cerevisiae a haploid cells, is post-translationally modified in a manner analogous to that of the ras proto-oncogene product. A consensus C-terminal amino acid sequence, -CAAX (C is cysteine, A is aliphatic amino acid, and X is any amino acid), is the target of these modifications, which include isoprenylation (essential for Ras function), proteolysis of the -AAX sequence, and carboxy methyl esterification. Recently, the RAM/DPR1 gene product was shown to be a component of the activity responsible for isoprenylation of both Ras and a-factor. In this report, we present an in vitro assay which not only detects a-factor isoprenylation, but also proteolysis and carboxy methyl esterification, and directly demonstrates, biochemically, the order of these processing events. This a-factor maturation assay may prove useful for screening agents which block any of the steps involved in the post translational modification of the a-factor and Ras -CAAX sequences. Such agents would be potential anti-Ras-related cancer therapeutic drugs. PMID- 2244915 TI - A new class of powerful inhibitors of monamine oxidase A. AB - It is well established that 1-methyl-4-phenylpyridinium (MPP), the neurotoxic bioactivation product of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and most of its analogs are good competitive inhibitors of monoamine oxidase A, with Ki values in the micromolar range, but they inhibit monoamine oxidase B only at much higher concentrations. We report here the finding that alkyl derivatives of MPP+ substituted at the 4' position of the aromatic ring are considerably more effective reversible inhibitors of the A type enzyme, with Ki values in the nanomolar range (0.075-1.6 microM). They inhibit the B type enzyme only at 2 to 3 orders of magnitude higher concentrations (32-374 microM). PMID- 2244916 TI - Translational efficiency: iridovirus early mRNAs outcompete tobacco mosaic virus message in vitro. AB - Infection with the iridovirus, frog virus 3, results in the rapid inhibition of host cell protein synthesis and is correlated with activation of an eIF-2 kinase. Because phosphorylation of eIF-2 inhibits ternary complex formation and thus reduces the overall level of translation, it has been suggested that frog virus 3 messages escaped translational shut-off by outcompeting host messages for the remaining translational capacity of the cell. In this report, we show that frog virus 3 messages were more translationally competitive than highly efficient tobacco mosaic virus transcripts based on their relative resistance to inhibitors of initiation. This result strengthens the suggestion that the selective translation of frog virus 3 transcripts in virus-infected cells may be a reflection of their enhanced competitiveness. PMID- 2244917 TI - All fifteen possible arrangements of three disulfide bridges in proteins are known. PMID- 2244918 TI - C-terminal KDEL-modified cystatin C is retained in transfected CHO cells. AB - The significance of a C-terminal tetrapeptide, Lys-Asp-Glu-Leu (KDEL), as a retention signal for the endoplasmatic reticulum was studied using cystatin C, a general thiol protease inhibitor, as the reporter protein. Clones of CHO cells were analyzed after stable transfection with eukaryotic expression vectors encoding either cystatin C, KDEL extended cystatin C, or cystatin C extended with a control sequence. It is concluded that cystatin C with the KDEL tetrapeptide as a C-terminal extension is retained intracellularly without apparent accumulation of the molecule. PMID- 2244919 TI - Purification of N-terminal hexapeptide of big gastrin from human urine. AB - We previously demonstrated that extremely high amounts of N-terminal big gastrin (G-34) fragments are excreted in human urine and three of them are N-terminal octa-, nona-, and decapeptide of G-34. Our subsequent examination revealed that there exists a considerable amount of another N-terminal G-34 fragment in urine, less hydrophobic than the three peptides. We purified this fragment from urine of an achlorhydric patient and determined the structure: less than Glu-Leu-Gly-Pro Gln-Gly. The purification was carried out by Sep-Pak C18 cartridges, Sephadex G 25, and reverse phase HPLC. The structure was determined by a combination of amino acid analysis, amino acid sequence analysis, and mass spectral analysis. N terminal hexapeptide of G-34 is the second richest component of urinary N terminal G-34 fragments next to N-terminal octapeptide of G-34 in normal subjects. PMID- 2244920 TI - Essential role of nitric oxide in descending inhibition in the rat proximal colon. AB - Possible mediators of descending inhibition in the rat proximal colon were studied. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. This relaxation was still observed after the colonic segment had been desensitized to ATP, neurotensin and vasoactive intestinal peptide, so these compounds seem unlikely to mediate descending inhibition. Nitro-arginine inhibited the relaxation induced by the distension, and L-arginine counteracted the effect of nitro-arginine. Nitric oxide, isoamylnitrate and sodium nitroprusside caused relaxation. These results strongly suggest an essential role of nitric oxide in descending relaxation in the rat proximal colon. PMID- 2244922 TI - Evidence for coenzyme Q function in transplasma membrane electron transport. AB - Transplasma membrane electron transport activity has been associated with stimulation of cell growth. Coenzyme Q is present in plasma membranes and because of its lipid solubility would be a logical carrier to transport electrons across the plasma membrane. Extraction of coenzyme Q from isolated rat liver plasma membranes decreases the NADH ferricyanide reductase and added coenzyme Q10 restores the activity. Piericidin and other analogs of coenzyme Q inhibit transplasma membrane electron transport as measured by ferricyanide reduction by intact cells and NADH ferricyanide reduction by isolated plasma membranes. The inhibition by the analogs is reversed by added coenzyme Q10. Thus, coenzyme Q in plasma membrane may act as a transmembrane electron carrier for the redox system which has been shown to control cell growth. PMID- 2244921 TI - Leukotriene A4 hydrolase: a zinc metalloenzyme. AB - Purified human leukotriene A4 hydrolase is shown to contain 1 mol of zinc per mol of enzyme, as determined by atomic absorption spectrometry. The enzyme is inhibited dose-dependently by the chelating agents 8-hydroxy-quinoline-5-sulfonic acid, and 1,10-phenanthroline with KI values of about 2 and 8 x 10(-4) M, respectively, whereas dipicolinic acid and EDTA are ineffective in this respect. The inhibition by 1,10-phenanthroline is time-dependent, and at a concentration of 5 mM, 50% inhibition of enzyme (3 x 10(-7) M) occurs after about 15 min. The zinc atom of leukotriene A4 hydrolase can be removed by dialysis against 1,10 phenanthroline which results in loss of enzyme activity. The catalytic activity is almost completely restored by the addition of stoichiometric amounts of Zn2+ or Co2+. PMID- 2244923 TI - Chelerythrine is a potent and specific inhibitor of protein kinase C. AB - The benzophenanthridine alkaloid chelerythrine is a potent, selective antagonist of the Ca++/phospholopid-dependent protein kinase (Protein kinase C: PKC) from the rat brain. Half-maximal inhibition of the kinase occurs at 0.66 microM. Chelerythrine interacted with the catalytic domain of PKC, was a competitive inhibitor with respect to the phosphate acceptor (histone IIIS) (Ki = 0.7 microM) and a non-competitive inhibitor with respect to ATP. This effect was further evidenced by the fact that chelerythrine inhibited native PKC and its catalytic fragment identically and did not affect [3H]- phorbol 12,13 dibutyrate binding to PKC. Chelerythrine selectively inhibited PKC compared to tyrosine protein kinase, cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase. The potent antitumoral activity of celerythrine measured in vitro might be due at least in part to inhibition of PKC and thus suggests that PKC may be a model for rational design of antitumor drugs. PMID- 2244924 TI - Comparison of kinetic parameters for acetylthiocholine, soman, ketamine and fasciculin towards acetylcholinesterase in liposomes and in solution. AB - Purified acetylcholinesterase from bovine brain was reconstituted by a detergent depletion technique into liposomes, prepared from soybean lecithin. The kinetics for the substrate acetylthiocholine and for three inhibitors with very different binding properties was studied. The results were compared with results from corresponding experiments with solubilized enzyme in detergent solution. The reconstituted enzyme showed a higher affinity for acetylthiocholine, ketamine and fasciculin. Parameters unaffected by the reconstitution were: turnover number for the substrate; the non-competitive component in ketamine inhibition and the kinetics for the active site-directed irreversible inhibitor soman. PMID- 2244925 TI - Thermodynamic study of the interaction of methotrexate, its metabolites, and new antifolates with thymidylate synthase: influence of FdUMP. AB - A microcalorimetric method was used for the direct study of the interaction of methotrexate, its metabolites, and new antifolates N10-propargyl-5,8 dideazafolate (CB 3717) and 2-methyl,2-desamino N10-propargyl-5,8-dideazafolate (CB 3819), with thymidylate synthase. We show that 7-hydroxymethotrexate and dideazafolates require the prior binding of dUMP or its fluorinated derivative FdUMP to bind to thymidylate synthase, as does methotrexate. Conversely, we show that methotrexate-G2 can interact directly with the enzyme alone. On the other hand, both dUMP and FdUMP exhibited a large cooperative effect on the affinity for thymidylate synthase of the inhibitors, and surprisingly, no significant difference was shown at this level between the natural substrate dUMP and its fluorinated derivative. It was demonstrated that this cooperative effect had an enthalpic origin. In the presence of FdUMP or dUMP, all the studied compounds except 7-hydroxymethotrexate exhibited a large negative enthalpy variation when binding to thymidylate synthase (from -44 to -91 kJ/mol). CB 3717 and methotrexate-G2 are competitors for the same protein binding site. Polyglutamation of methotrexate lead to compounds with higher affinity (association constants were 6.6 x 10(3) M-1 and 2.3 x 10(6) M-1 for methotrexate and methotrexate-G2 respectively) while hydroxylation has an unfavourable effect (association constant of 7-hydroxymethotrexate inferior to 500 M-1). Evidence for the influence of polyglutamation was also provided by the relatively low affinity of dideazofolates for thymidylate synthase (association constant equal to 1.4 and 1.7 x 10(7) M-1 for CB 3717 and CB 3819, respectively), whereas these compounds are known to be strong inhibitors of the enzyme in cells in their polyglutamated forms. PMID- 2244926 TI - Nafenopin, a hypolipidemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates. AB - Addition of nafenopin (30-300 microM to 45Ca2+ preloaded cultured hepatocytes caused a rapid and concentration-dependent increase in 45Ca2+ efflux in a manner similar to vasopressin, as evidenced by the loss of radioactivity from the cells. In contrast to vasopressin, addition of nafenopin to [3H]inositol prelabelled hepatocytes in culture did not increase [3H]inositol phosphate production. When added simultaneously with vasopressin, nafenopin inhibited the vasopressin stimulated [3H]inositol phosphate production. In hepatocyte suspensions isolated from rats treated for 1 week with a carcinogenic dose of nafenopin (1000 ppm in their daily food) the incorporation of [3H]inositol into the phosphoinositide fraction, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, was much less than that in hepatocytes isolated from untreated rats. The vasopressin-stimulated [3H]inositol phosphate production was also decreased. Experiments with hepatocyte suspensions preloaded with Ca2+ or pH sensitive fluorescent indicators demonstrated that addition of nafenopin caused an increase in intracellular free Ca2+ and transient acidification of the cells. The increase in [Ca2+]i was decreased by only about 25% when extracellular calcium was removed indicating that nafenopin mainly mobilizes Ca2+ from intracellular stores. The recovery to basal pH was amiloride-sensitive indicating the importance of Na+/H+ exchange in pH recovery after intracellular acidification. Amiloride also inhibited DNA synthesis induced by nafenopin and by epidermal growth factor in cultured hepatocytes; but this effect occurred concomitantly with inhibition of basal DNA synthesis. We suggest that hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses. PMID- 2244927 TI - Influence of S-adenosylhomocysteine hydrolase inhibitors on S adenosylhomocysteine and S-adenosylmethionine pool levels in L929 cells. AB - S-Adenosylhomocysteine hydrolase has been recognized as the target enzyme for the antiviral activity of several carbocyclic and acyclic adenosine analogues. In a previous study [Cools M and De Clercq E, Biochem Pharmacol 38: 1061-1067, 1989], we found a close correlation between the antiviral activity of six adenosine analogues [S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], (RS)-3-adenin-9-yl-2 hydroxypropanoic acid [(RS)-AHPA] (isobutyl ester), 3-deazaneplanocin A, carbocyclic 3-deazaadenosine (C-c3 Ado), adenosine dialdehyde and neplanocin A) against vaccinia virus and vesicular stomatitis virus and the inhibitory effect of these compounds on purified AdoHcy hydrolase isolated from murine L929 cells. We have now examined the effects of the different adenosine analogues on the intracellular pool levels of S-adenosylhomocysteine (AdoHcy) and S adenosylmethionine (AdoMet). Treatment of vaccinia virus-infected L929 cells for 24 hr with the adenosine analogues at a dose that reduced vaccinia virus growth by 90% (ID90) increased the average AdoHcy pool levels from 0.027 nmol/mg protein to approximately 0.3 nmol/mg protein and the AdoHcy/AdoMet ratio from 0.038 to approximately 0.3. Moreover, the AdoHcy/AdoMet ratio correlated closely with the vaccinia virus yield reduction, both determined over the 24-hr post infection period (correlation coefficient of 0.972). These findings indicate that the activity of the AdoHcy hydrolase inhibitors against vaccinia virus may be related to the raise in intracellular AdoHcy pool levels and AdoHcy/AdoMet ratio. PMID- 2244928 TI - Inhibitory effect of unstimulated neutrophils on platelet aggregation by release of a factor similar to endothelium-derived relaxing factor (EDRF). AB - Previous studies have indicated a possible role for polymorphonuclear leukocytes (PMNLs) in the maintenance of hemostasis and vascular tone. We now demonstrate that unstimulated isolated PMNLs maintained at 37 degrees inhibited human platelet aggregation in a concentration- and time-dependent fashion. In addition, PMNLs increased platelet cyclic GMP concentrations. The platelet aggregation inhibitory effect of PMNLs was potentiated by superoxide dismutase and attenuated by hemoglobin and methylene blue. This inhibitory effect of PMNLs was not observed in 48-hr-old killed cells and was not modulated by aspirin treatment or by adenosine deaminase. These observations suggest that human PMNLs maintained at 37 degrees produce a substance with biological characteristics similar to those of the endothelium-derived relaxing factor. PMID- 2244929 TI - Metabolism of the 4-iodo derivative of tamoxifen by isolated rat hepatocytes. Demonstration that the iodine atom reduces metabolic conversion and identification of four metabolites. AB - The 4-iodo derivative of tamoxifen, which has been reported to possess improved oestrogen receptor affinity and effectiveness as an inhibitor of breast tumour cell growth in vitro, was metabolized by hepatocytes isolated from rats pretreated with phenobarbital four times more slowly than tamoxifen and there was very little formation of glucuronide conjugates. Four principal metabolites were isolated. Examination of mass spectra revealed desmethyl-4-iodotamoxifen, 4 iodotamoxifen N-oxide, and alpha-hydroxydesmethyl-4-iodotamoxifen (4-[4-[2 (methylamino)ethoxy]phenyl]-4-(4-iodophenyl)-3-phenyl-but-3- (Z)-en-2-ol). Their identification was confirmed by comparison with synthesized samples. The structure of the fourth metabolite, 4'-hydroxy-4-iodotamoxifen was revealed by 1H NMR spectroscopy. The iodophenyl moiety is thus retained in all the metabolites. The iodine atom not only blocks metabolism in its vicinity but also reduced the rate of side-chain demethylation and N-oxidation by three-fold. It can be predicted from this study that the presence of the iodine atom should give the compound a greater duration of action in vivo. PMID- 2244930 TI - The interaction of oral hypoglycaemic drugs with insulin on steroid metabolism in hepatocytes isolated from control and diabetic male rats. AB - The effects of the oral hypoglycaemic drugs, phenformin and tolbutamide, and insulin, alone and in combination, on steroid metabolism in hepatocytes isolated from control and streptozotocin-diabetic male rats has been studied. Both phenformin and tolbutamide mimic the action of insulin in stimulating hepatic steroid metabolism in a dose-dependent manner in control cells. Unlike insulin, however, both drugs give a similar effect in cells derived from diabetic animals although to a lesser extent. Both drugs can partially restore the effect of insulin in cells derived from diabetic animals. Biguanides and sulphonylureas, therefore, have a direct effect on liver cells to mimic insulin action and can still have an effect under conditions where insulin is inactive. Both types of oral hypoglycaemics can also affect insulin-insensitive cells isolated from diabetic rat liver to restore to a certain extent their response to insulin. PMID- 2244931 TI - Differential inhibition of nucleoside transport systems in mammalian cells by a new series of compounds related to lidoflazine and mioflazine. AB - The sensitivity of facilitated-diffusion and Na(+)-dependent nucleoside transporters to inhibition by a series of novel compounds related to lidoflazine and mioflazine was investigated. Uridine transport by rabbit erythrocytes, which proceeds solely by the nitrobenzylthioinosine (NBMPR)-sensitive facilitated diffusion system, was inhibited with apparent Ki values of less than 10 nM by lidoflazine, mioflazine, soluflazine and R73-335. These compounds also blocked site-specific [3H]NBMPR binding to rabbit erthrocyte membranes in a competitive fashion. The NBMPR-sensitive system in rat erythrocytes was also inhibited by lidoflazine, mioflazine, soluflazine and R73-335 but was two to three orders of magnitude less sensitive to inhibition than the system in rabbit erythrocytes (apparent Ki 7.3, 2.4, 5.7 and 0.1 microM, respectively). Lidoflazine, mioflazine and R73-335 exhibited a similar potency for the NBMPR-sensitive and -insensitive nucleoside transporters in rat erythrocytes. In contrast, soluflazine was 20- to 100-fold more potent as an inhibitor of the NBMPR-insensitive nucleoside transport component in rat erythrocytes (IC50 of 0.08-0.2 microM) compared to the NBMPR-sensitive nucleoside carrier in these cells (IC50 approximately 10 microM). None of the test compounds were potent inhibits of Na(+)-dependent uridine transport in bovine renal brush-border membrane vesicles. These results indicate that lidoflazine, mioflazine, soluflazine and R73-335 are selective inhibitors of nucleoside transport in animal cells and that the potency of these compounds as nucleoside transport inhibitors is species dependent. PMID- 2244932 TI - Purification and immunochemical characterization of a rat liver sulphotransferase conjugating paracetamol. AB - Paracetamol sulphotransferase (ST) was purified 250-fold from male rat liver, and the pure enzyme used to elicit antibodies in rabbit. The enzyme was active towards paracetamol at pH 9.0, as well as towards several commonly used drugs, and formed sulphates at both O- and N-atoms. Comparison of the substrate specificity of paracetamol ST with that of aryl sulphotransferases isolated by other workers suggested that we have purified a previously unknown isoenzyme of rat liver ST, although the difficulties of characterization of STs based on their substrate specificities is noted. The antibody preparation recognized only one polypeptide (Mr = 35,000) on immunoblot analysis of rabbit liver cytosol, corresponding to purified paracetamol ST. Analysis of the tissue distribution of this protein demonstrated that its expression was restricted to the liver, as was the enzyme activity. The observed sex difference in paracetamol ST (males greater than females) was determined by immunoblot analysis to be the result of reduced enzyme protein levels in females. In human liver cytosol, the antibody recognized two polypeptides, probably corresponding to M- and P-phenol STs, suggesting significant sequence similarity between rat and human phenol sulphotransferases. PMID- 2244934 TI - Indomethacin attenuation of celiac blood flow hyperemia following glutathione depletion. AB - The effect of glutathione (GSH) depletion on mean celiac blood flow (MCBF) was determined in domestic fowl. Diethyl maleate (DEM, 1 mL/kg body wt) decreased hepatic and duodenal GSH to approximately 15% of control. This GSH depletion was associated with an increase in MCBF and decreases in mean arterial blood pressure (MABP) and celiac vascular resistance (CVR). While indomethacin attenuated the rise in MCBF, this cyclooxygenase inhibitor had no effect on the decrease of MABP or CVR which occurred following DEM treatment. The results indicate that GSH depletion may increase vasodilatory prostaglandin synthesis since elevations in MCBF were attenuated by cyclooxygenase inhibition. PMID- 2244933 TI - Effect of thromboxane synthetase inhibition and angiotensin converting enzyme inhibition on acute cyclosporin A nephrotoxicity. AB - One component of cyclosporin A (CsA) nephrotoxicity is thromboxane (Tx) A2 induced renal vasoconstriction. This study was designed to investigate whether coadministration of angiotensin converting enzyme inhibitors (ACEI) and thromboxane synthetase inhibition (TSI) could act synergistically to improve the glomerular filtration rate in CsA treated animals. CsA administration (50 mg/kg/day p.o.) to Sprague-Dawley rats for 14 days caused a significant decline in creatinine clearance (CCR), an increase in N-acetyl-beta-D-glucosaminidase (NAG) enzymuria and renal tubulointerstitial damage. These changes were associated with a ten-fold increase in urinary TxB2 excretion (from pretreatment values of 17.2 +/- 6.0 ng/day to 174.9 +/- 65.4 ng/day on day 14). Treatment with TSI normalized TxB2 excretion; this was associated with partial protection against CsA induced changes in CCR and NAG enzymuria and the complete prevention of acute proximal tubular vacuolation. However, the coadministration of both TSI and ACEI removed the protective effects exerted by TSI alone and resulted in elevated urinary TxB2 levels similar to those observed in other CsA treated groups. Treatment with ACEI alone did not affect CsA nephrotoxicity. We suggest that elevated TxB2 synthesis is in part responsible for some aspects of renal functional and morphological damage, but that CsA nephrotoxicity is multifactorial and may result from direct cellular toxicity in addition to vascular changes. PMID- 2244935 TI - Stimulatory effect of 4-alkylcatechols and their diacetylated derivatives on the synthesis of nerve growth factor. AB - A series of 4-alkylcatechols and 1,2-diacetoxy-4-alkylbenzenes (from methyl to butyl) were chemically synthesized for in vitro evaluation as stimulators of nerve growth factor (NGF) synthesis. All compounds were proven to be potent in stimulating NGF synthesis in L-M cells (a mouse fibroblast cell line) and mouse astroglial cells. In a series of 4-alkylcatechols, 4-methylcatechol and 4 ethylcatechol severely affected viability and cell adhesive properties. In a series of 1,2-diacetoxy-4-alkylbenzenes, the concentrations required for the maximal effect and the effective ranges of concentrations were higher than those in the 4-alkylcatechol series, and the cell adhesive properties or viabilities were not affected. Evidence is also presented to indicate that the elevation of NGF synthesis by these compounds was not associated with the cell growth. PMID- 2244936 TI - Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. AB - Cell death induced by cisplatin was studied in Chinese hamster ovary cell lines, one proficient and the other deficient (100-fold sensitive) in DNA excision repair. Previous experiments demonstrated that cells progressed to and arrested in the G2 phase of the cell cycle before dying. DNA double-strand breaks were detected following G2 arrest and prior to loss of membrane integrity. These DNA breaks have been studied in more detail. DNA fragments were observed consisting of multimers of approximately 180 base pairs. These fragments are consistent with internucleosomal cleavage of chromatin by an endonuclease. At LC90 concentrations, DNA digestion began 48 hr cisplatin treatment followed by loss of membrane integrity and cell shrinkage 24 hr later. High concentrations of cisplatin (170 logs of kill) induced DNA digestion 12 hr after drug treatment but loss of membrane integrity occurred 12 hr later. Both cell death and DNA fragmentation were inhibited by cycloheximide, suggesting the requirement for new protein synthesis. Cells incubated with many other agents demonstrated the same characteristic pattern of DNA degradation. At 90% lethal conditions, DNA digestion was induced within 30 min by hyperthermia, 18 hr by methotrexate, and 48-72 hr by all other agents tested. DNA digestion always preceded loss of membrane integrity and cell shrinkage. These observations are consistent with cell death occurring by the process of apoptosis, or prorammed cell death, and demonstrate the importance of DNA digestion as an early and presumably essential step in cell death. The results suggest that, irrespective of the primary site of action of a drug, cell death by most pharmacologic agents is mediated by activation of the signal transduction pathway for apoptosis. The results also suggest two signal pathways for apoptosis, one directly associated with drug action and a second that requires cell cycle-related events. PMID- 2244937 TI - Antioxidant enzymes in Acanthocheilonema viteae and effect of antifilarial agents. AB - Adult worms of Acanthocheilonema viteae were found to be susceptible to the reactive oxygen intermediates (ROI) generated by the xanthine-xanthine oxidase (X XO) system. The damage caused by this system was completely abolished by superoxide dismutase (SOD) and catalase but not by mannitol. The results, therefore, suggest that superoxide anions (O2-) and hydrogen peroxide (H2O2) alone or in combination might be toxic to the filariid. A. viteae exhibited the presence of an active enzyme system to protect itself against the oxidants. SOD and catalase were present in high levels of activities and appeared to constitute the major defence system. The role of glutathione peroxidase (GPx), on the other hand, seemed less important due to the weak activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). A. viteae also released SOD, catalase and GPx in the ambient medium, which appear useful in protecting the filariid against ROI generated by the host in the immediate surroundings of the parasite. Antifilarial agents, diethylcarbamazine (DEC) and 2,2' dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (82/437) appreciably inhibited catalase and GPx of A. viteae. Inhibition of these enzymes appears to render the parasite prone to H2O2 toxicity leading to death. No adverse effect on antioxidant enzymes of liver, lungs and subcutaneous tissue of Mastomys natalensis recorded as a result of exposure to 82/437 suggests a non-toxic nature to the compound. PMID- 2244938 TI - Effects of tumor promoters on adenylate cyclase activity in melanoma cells in culture. PMID- 2244939 TI - Substrate specificity of guinea pig liver flavin-containing monooxygenase for morphine, tropane and strychnos alkaloids. PMID- 2244940 TI - I want to be a nurse, not a stereotype. PMID- 2244941 TI - The Masters Degree in Medical Physics at Queensland University of Technology--14 years on. AB - In 1975, the Masters Degree in Medical Physics was first made available at the Queensland Institute of Technology (now Queensland University of Technology, QUT), and is offered on both a part time and full time basis. An option for a Graduate Diploma award after completion of the in-house course work stage is available. The research project may be undertaken either in Brisbane or elsewhere. Such projects have been undertaken in Perth, Hong Kong, Sydney, etc. It is a broad based program, embracing activities of current professional importance while including aspects which have potential importance. Recognition that medical physics is a dynamic speciality ensures that the content of the program is kept under continuous review, and changes made as required. It is of interest to observe that of graduates from the course, approximately 50% have moved into the hospitals and private medical research, 11% into government health departments, 16% into the mining industry, 9% into tertiary education, and 14% into non medical or sales areas. Many have gained senior positions in their selected vocations. The success of the program in providing a useful professional person is due in no small measure to the collaboration of many dedicated professionals in the field. This collaboration relates to informal and formal contact between academic staff and students within the Physics Department, and personnel in hospitals, public health establishments and industry. PMID- 2244942 TI - [Biopolymers with antitumor and immunomodulating action]. PMID- 2244943 TI - Protein structure. The changing shape of actin. PMID- 2244944 TI - Mobile C-arm units. AB - Mobile C-arm units, so named because of their configuration, are used primarily for fluoroscopic imaging during surgical, orthopedic, critical care, and emergency care procedures. They also provide radiographic capability, although they are rarely used for this imaging modality. We evaluated three mobile C-arm units from three manufacturers. We based our ratings on the ability of the units to safely and reliably produce the best possible image quality while delivering the lowest possible radiation dose to the patient and protecting personnel from radiation exposure; we also considered human factors design. The Philips BV 25 N is rated Acceptable and is preferred as a general-purpose unit. The OEC-Diasonics 9000/6 is also rated Acceptable and may be preferred when the hospital has specific uses for its optional specialty modules. The Fischer Ortho-Omni 325 is rated Acceptable-Not Recommended because of its relatively high patient exposure rates, poorer object thickness compensation (penetration) capability, poorer spatial resolution, and overall poor human factors design compared with the other evaluated units. Also see "Issues of Radiation Exposure" and "Ensuring Optimum Performance." PMID- 2244945 TI - Clinical services provided by staff pharmacists in a community hospital. AB - A program for developing staff pharmacists' clinical skills and documenting pharmacists' clinical interventions in a large community teaching hospital is described. A coordinator hired in 1984 to develop clinical pharmacy services began a didactic and experiential program for baccalaureate-level staff pharmacists. Fourteen educational modules are supplemented by journal and textbook articles and small-group discussions of clinical cases, and the clinical coordinator provides individual training on the patient-care units for each pharmacist. Monitoring of clinical pharmacy services began in June 1987; each intervention provided by a pharmacist is recorded on a specially designed form. A target-drug program is used to document cost avoidance achieved through clinical services. Information collected through these monitoring activities is used to educate the pharmacy staff, shared with the pharmacy and therapeutics committee, and used to monitor prescribing patterns of individual physicians. The data are used in the hospital's productivity-monitoring system. All pharmacists who were on staff in 1984 have completed the educational modules, and all new employees are in the process. Since monitoring began, the number of clinical interventions has averaged 2098 per month. Cost avoidance has averaged $9306 per month. Over a five-year period, the development of staff pharmacists' clinical services raised the level of professional practice, produced substantial cost avoidance, and increased the number of pharmacist interventions in medication use. PMID- 2244946 TI - Comparison of two self-instructional manuals on adverse drug reaction monitoring. PMID- 2244947 TI - [Long-term study following frontolateral partial larynx resection]. AB - Between 1972 and 1981 frontolateral laryngectomy was performed in 72 cases of vocal cord cancer. Regular follow-up examinations were performed over a period of at least five and up to 15 years after primary surgery. In 1987, 63 of these patients were still alive. In 68 out of 72 (94.3%), survival time was three years or more. In 34 out of 43 (79%), survival time was five years or more. Leroux Robert's indication guidelines are confirmed and slightly extended. The functional results and the frequency of recurrence are reviewed. PMID- 2244948 TI - [Hypopharyngeal carcinoma and radical surgery--does such a therapeutic procedure make sense?]. AB - From 1977 to 1983, 49 patients with carcinoma of the hypopharynx were treated, including follow-up, at the ENT clinic of the Zentralkrankenhaus St. Jurgen Strasse in Bremen. Two groups of patients with comparable tumor stage distributions were either treated with a combination of radical surgery and radiotherapy (19 patients), or not operated at all, receiving instead radiotherapy and/or chemotherapy (30 patients). The five-year survival rates (33% and 11% respectively) revealed, albeit at an altogether low level, the superiority of the radical procedure, including total extirpation of the larynx. The recommendation for radical removal of a hypopharyngeal carcinoma must therefore be made on an individual basis and with some reservation. Compromises, such as surgical management of the lymph node metastases without extirpation of the primary tumor, which is then irradiated, or the excision of the primary tumor in combination with partial resection of the larynx, ought to be made when choosing between possible therapeutic alternatives. PMID- 2244949 TI - [Subjective and objective voice assessment following partial resection of the larynx]. AB - There is no generally accepted, standardized approach for evaluation of voice quality and of intelligibility after partial laryngectomy. A voice evaluation which considers some aspects of voice quality is possible by assessing physical and acoustic voice parameters. But this approach does not consider how the patient subjectively assesses his postoperatively altered voice and how the patient believes he is understood by various communication partners. In this study objective and subjective variables of the voice quality of 32 patients with partial laryngectomies were measured. First, selected physical and acoustic variables of voice quality were quantified. Second, subjective criteria of voice quality and of intelligibility were assessed by a questionnaire. A significant correlation between variables of objective and subjective voice quality was found. The maximum vocal intensity, the maximum pitch, and the intensity range correlated significantly with the subjective assessment of intelligibility. No relationship was found between the acoustic variables and the subjectively perceived degree of vocal disability. PMID- 2244950 TI - [Rehabilitation of deglutition in patients with pharyngeal carcinoma]. AB - Surgical treatment of pharyngeal carcinoma implies different reconstructive procedures. Despite primary healing, in some cases cicatricial shrinkage occurs, resulting in dysphagia. Of 113 patients with carcinoma of the oro- and hypopharynx in the last 4 years, 35 patients were studied in a specific follow-up examination. Deglutition was evaluated via subjective responses to a questionnaire. Reproducible information was gained by videofluoroscopy and manometry of the pharyngo-esophageal segment. To assess deglutition, an arbitrary number scale was established with 7 for excellent and 1 for poor deglutition. After local tumour excision, partial and total pharyngectomy, pharyngolaryngectomy and additional myocutaneous grafting, the deglutition index ranged from 5.8 to 4.5 showing more striking differences in the time required for eating. Manometric analysis showed pressure peaks 10 times lower (3.5 hPa) than in normal subjects with prolongation of each swallow. Videofluoroscopy reveals even slight motility disturbances after ablative pharyngeal surgery. Typical findings are presented. The swallowing function after pharyngeal tumour operations requires the reconstruction of both the horizontal (oral) and vertical (pharyngeal) phase of deglutition. Since the base of the tongue seems to be the major driving force in bolus movement, it is not the extension of resection but the availability of remaining contractile tissue in the neopharynx, especially in the base of the tongue region, that determines the postoperative rehabilitation of deglutition. PMID- 2244951 TI - [Etiology and clinical aspects of palatal myoclonus]. AB - Palatal myoclonus is a movement disorder consisting of rhythmic myoclonus of the soft palate, pharynx, larynx, and other muscles derived from the embryonal branchial arches. These movements are continuous and involuntary, and the patients are, in general, unaware of them. In the majority of patients, palatal myoclonus persists for life. In oculopalatal myoclonus, the eyes can be involved in the form of a nystagmus. Often a clicking noise in one or both ears is the initial symptom which can be heard by the examiner. A variety of etiologies have been linked to palatal myoclonus. The most common defined cause is a stroke. The variable delay between the proposed cause and the appearance of the disorder causes difficulties in determining the exact etiology. Pathologic findings show a transsynaptic hypertrophic degeneration of the inferior olivary nucleus which is due to a lesion of a specific, inhibitory, anatomic pathway. This somatotopic pathway leaves the contralateral dentate nucleus, passes through the superior cerebellar peduncle, and crosses the posterior commissure before joining the central tegmental tract and descending to the ipsilateral inferior olive. Treatment of palatal myoclonus is only occasionally effective. Some patients have responded to tryptophan, carbamazepine, and trihexyphenidyl. Surgical attempts have not been successful. - In the present paper the authors report on a case of an oculopalatal myoclonus following Leber's optic atrophy which involved the brain stem. PMID- 2244952 TI - [Diagnosis and therapy of myo-arthropathy (Costen's syndrome)]. AB - The temporo-mandibular joint (TMJ) syndrome was first described by Costen in 1936. It is a muscular-skeletal pain-disease. The pain is caused by hypertonia of the masticatory muscles and is projected into various regions of the head and neck. There is a primary dysfunctional etiology as well as a secondary etiology based on other diseases, particularly of the ENT region. Diagnostically, therefore, a process of exclusion is required. The symptoms can range from diffuse headache and facial pain to strictly localized or even neuralgic pain. Otogenic symptoms may be pain or various noises in the ear. For differential diagnosis, most of the painful diseases of the head area must be considered because of the multiform clinical manifestation of the TMJ syndrome. The treatment of the TMJ syndrome follows a multistep scheme that includes behavior therapy, physiotherapeutic methods, and occlusal therapy. PMID- 2244953 TI - [Use of B-mode sonography in the diagnosis of laryngocele]. AB - A case of a combined laryngocele is presented, including clinical features, the histopathological findings, and the treatment of the disease. The article stresses the value of imaging methods such as CT-scan and high-resolution real time sonography for preoperative diagnosis. Especially note-worthy is the fact that the internal and external parts of laryngoceles, filled with fluid and with air, can be shown by sonography. PMID- 2244954 TI - [Ultrasonic diagnosis of the tongue]. AB - Ultrasonic diagnosis of the tongue supplements inspection and palpation, and, aside from computerized tomography and, in particular, nuclear spin tomography, broadens our knowledge. By way of introduction, transcutaneous treatment using the submental sound-scanner in "B" mode is described. If necessary, examination can be performed simultaneously in the "B" and "M" modes. Attention is drawn to the significance of the 5 cm distance between the floor of the mouth and the surface of the tongue. Indications range from the diagnosis of tongue carcinoma, including relapse diagnosis, to dynamic functional tests of neurological disorders and visual biofeedback in phoniatrics and logopedics. Median-line diagnosis is of critical importance in tongue carcinoma. Ultrasonic diagnosis of the tongue can be recommended as a simple and cost-saving routine method. PMID- 2244955 TI - [The value of 3D proton spin tomography reconstruction as exemplified by an extensive parotid adenoma]. AB - In the past few years, 3 D reconstruction has been established as a new imaging method in various medical fields, such as orthopedic surgery and neurosurgery. In a former article, the authors introduced a new 3 D imaging method for the head and neck. The present study reports the case of a 37-year-old woman with a huge adenoma of the parotid gland. The tumor grew along the skull base, protruding onto the left tonsil. The diagnostic value of the authors' reconstruction method for lesions in the head and neck is discussed. The results indicate that this technique might be of significant clinical importance for special questions arising in the head and neck region as well as for preoperative planning in the case of certain tumors. PMID- 2244956 TI - [Differential diagnosis and therapy of vertigo of vertebral origin]. AB - The following questions are discussed: Does vertigo of purely cervical functional origin really exist with clinical importance? How can it be determined by differential diagnosis? How can the ENT physician treat cervical vertigo? PMID- 2244958 TI - Environment and health. The European Charter and Commentary. First European Conference on Environment and Health. Frankfurt, 7-8 December 1989. PMID- 2244957 TI - [Esophageal caustic injury in childhood. A critical elucidation with indication for esophagoscopy]. AB - From 1983 through 1988, esophagoscopies were performed in 41 children because of suspected caustic esophageal injury. Of these 41 children, 11 had endoscopically significant esophageal burns and were treated with steroids and antibiotics. Of these 11 patients, two had no chemical burns of the facial skin, mouth, or pharyngeal mucosa. The authors therefore believe that esophagoscopy must not be omitted in cases of suspected caustic ingestion. PMID- 2244959 TI - Expression cloning of tumor suppressor genes: a guide for optimists. PMID- 2244960 TI - Ki-ras activation and expression in transformed mouse lung cell lines. AB - The Ki-ras proto-oncogene is activated by specific point mutations and is the transforming gene often identified in rodent and human lung tumors. An in vitro model to aid in the study of the consequences of Ki-ras activation and expression in mouse lung is needed. Accordingly, we have examined cell lines derived from chemically induced mouse lung tumors as well as spontaneous transformants of untreated mouse lung epithelial cells. The specific Ki-ras-activating gene mutations and the level of mRNA expression were examined for each cell line. Polymerase chain reaction and oligonucleotide hybridization were used to demonstrate that five of seven transformed lung cell lines contain codon 61 Ki ras-activating mutations, resulting in an arginine substitution for wild-type glutamine. One transformed line contained this activating mutation and had also lost, or contained an altered, wild-type codon 61 Ki-ras allele. No codon 12 Ki ras mutations were observed. Two transformed and two nontransformed epithelial lung cell lines contained only the wild-type codon 12 and 61 Ki-ras alleles. Northern blot analysis demonstrated that the Ki-ras mRNA was present in all the cell lines and was overexpressed in some, but not all, of the transformed lung cell lines. Those transformed lines with the highest levels of Ki-ras mRNA also expressed more H4-histone mRNA, suggesting that these cells have a greater proliferation rate. The level of Ki-ras mRNA increased during the proliferation of the nontransformed lung cells but then decreased upon reaching confluency. In contrast, the level of Ki-ras mRNA in the transformed lung cells was high during both growth and confluency, suggesting a potential defect in the regulation of Ki ras in these cells. These lung cell lines will help provide a better understanding of the regulation of both the Ki-ras proto-oncogene and oncogene in the lung. PMID- 2244961 TI - Specific Ki-ras codon 61 mutations may determine the development of urethan induced mouse lung adenomas or adenocarcinomas. AB - In A/J strain mice, the carcinogen urethan induces lung adenomas and adenocarcinomas that contain Ki-ras-activating mutations primarily in codon 61. These mutations affect the middle adenine in codon 61 resulting in the substitution of either arginine (AT----GC transition) or leucine (AT----TA transversion) for the wild-type glutamine. To analyze the expression of the wild type and mutant Ki-ras mRNAs in primary mouse lung tumors and transformed mouse lung cell lines, we utilized reverse transcription of total mRNA and DNA amplification by the polymerase chain reaction. The wild-type allele of codon 61 was expressed in all normal lung and primary tumor samples and in all transformed cell lines, except one. Significantly, the leucine-substituted allele was expressed primarily in very small lung adenomas, whereas the arginine-substituted allele was expressed in large lung adenocarcinomas and transformed lung cell lines. The relative amounts of expression of the mutant versus wild-type Ki-ras alleles and the total Ki-ras mRNA expression was similar in both lung adenomas and adenocarcinomas. Further, the arginine mutant allele was present in adenocarcinomas having either alveolar or papillary tumor morphologies. These results suggest that the specific activating Ki-ras mutation is more critical to either lung adenoma or adenocarcinoma development than is the tumor's cell of origin or the extent to which the mutant alleles are expressed. A distinct role of the specific activating Ki-ras mutations in affecting lung tumor growth or malignant potential is indicated. PMID- 2244962 TI - Metabolic effects of C21 steroids in female Epinephelus akaara (Teleostei: Serranidae). AB - Cortisol, 11-deoxycorticosterone, progesterone, 17 alpha-hydroxy-progesterone, 17 alpha-hydroxy-20 beta-dihydroprogesterone, or a combination of the last 2 steroids, were injected into different groups of immature female Epinephelus. None of the steroids tested had significant effects on serum electrolyte level, and hepatosomatic and gonadosomatic indices. Serum glucose concentration was elevated after treatment with cortisol, 11-deoxycorticosterone, 17 alpha-hydroxy 20 beta-dihydroprogesterone or a combination of 17 alpha-hydroxy-20 beta dihydroprogesterone and 17 alpha-hydroxyprogesterone. Muscle protein concentration was lowered after treatment with cortisol, 17 alpha-hydroxy-20 beta dihydroprogesterone or a combination of 17 alpha-hydroxyprogesterone and 17 alpha hydroxy-20 beta-dihydroprogesterone. Liver protein was significantly elevated after treatment with progesterone but lowered after cortisol treatment. The results suggest that oocyte maturation is an energy consuming process, and that steroid hormones regulating these processes, including 17 alpha-hydroxy-20 beta dihydroprogesterone and 11-deoxycorticosterone adjust metabolism to provide energy for these processes. PMID- 2244963 TI - [Explanation and prediction of the kinetics of degradation in a Rusitec fermentor of nitrogenous vegetable matter after cell wall fractionation]. AB - The relation between nitrogen solubility in Van Soest detergents and in vitro nitrogen degradation was studied on 11 substrates with degradation process calculations in digestive trials and an artificial semi-continuous flow (Rusitec) rumen. The kinetics of plant protein degradation in Rusitec, especially the maximum degradation values, were rather similar to those calculated from literature data obtained in situ. In the exponential model used to describe the protein degradation, the maximum disappearance (a + b) was negatively correlated with the percentage of acid detergent insoluble nitrogen in the Van Soest (ADIN/Total N). In the foods tested, the non degradable fraction corresponds to a quantity which is equivalent to approximately 76% of the ADIN fraction. The instantaneously degraded nitrogen (a) was rather well explained by the percentage of neutral detergent insoluble nitrogen in the Van Soest (NDIN/Total N). The rate of disappearance (c) of the slowly degraded fraction was inversely correlated with the proportion of ADF in the NDF, which demonstrates the latter's resistance to degradation. This type of fractionation could be used in predicting nitrogenous value of feed stuffs for ruminants. PMID- 2244964 TI - Lack of effect of exogenous insulin-like growth factor-I (IGF-I) on chick embryo growth rate. AB - Direct evidence that IGF-I has any significant effect on embryo growth is lacking. We therefore studied the effect of administration of IGF-I on the chick embryo in ovo. Five hundred ng pure IGF-I (purified from human plasma) were given to chick embryos on 2 occasions (7 and 14 d) by injection directly into the allantoic sac. Treated and control (saline injected) chicks hatched on the same day and were killed. IGF-I appeared to reach the tissues as the [35S]-sulphate uptake of treated sternal cartilage was significantly greater than that of control (P less than 0.02). However, there were no significant effects of treatment on total body weight, bone length measurements, organ (lung, liver, heart) weights, muscle DNA, RNA or protein levels. From these results we conclude that administration of exogenous IGF-I to the chick embryo at 7 and 14 d does not stimulate further growth of the chick embryo. PMID- 2244965 TI - Changes in muscle fiber populations and muscle enzyme activities in the primiparous lactating sow. AB - An experiment involving 12 primiparous Large White sows was conducted to investigate changes in contractile and metabolic characteristics of skeletal muscle during the first 3 weeks of lactation. The sows lost 19.7 +/- 6.6 kg of body weight. No change in DNA concentration was observed in the longissimus dorsi (LD), a fast-twitch glycolytic muscle, and the trapezius (T), a mainly slow twitch oxidative muscle during lactation. The percentage of type I fibers increased (P less than 0.05) in LD, but not in T. The muscle fiber cross sectional area (CSA) of IIB fibers, which represents about 78% of the total number of LD fibers, decreased by 18% (P less than 0.01) by lactation; the CSAs of I and IIA fibers were not significantly affected. Marker enzyme activities for oxidative and glycolytic metabolisms decreased in both muscles during lactation. The decrease in oxidative enzyme activities was particularly dramatic in T (P less than 0.001). No significant relationship was observed between sow weight loss and changes in muscle fiber CSA or enzyme activities. The extent to which the results could be related to a negative nutritional balance or to changes in hormonal status is discussed. PMID- 2244966 TI - Microbial degradation in the rumen of wheat straw and anhydrous ammonia treated wheat straw observed by electron microscopy. AB - With the exception of the phloem and the crown of the parenchyma, which borders the medullary lacuna, the walls of the tissues of both treated and untreated straw were lignified. The walls of the treated straw were not fluorescent in the ultraviolet probably because the treatment had modified the phenolic acids. They also had a stronger reaction to Schiff reagent particularly in the sclerenchyma indicating that their polysaccharides were more accessible. The tissues of the treated straw degraded faster in the rumen. The walls of the sclerenchyma of the treated straw were attacked by micro-organisms. Both treated and normal straw were abundantly colonized by rumen fungi, especially in the sclerenchyma. The increase in the digestibility of the treated straw was due to the greater access the micro-organisms had to the polysaccharides of the lignified walls. PMID- 2244967 TI - [Effects of alginates and sodium carrageenates mixed with soy proteins on the coefficient of protein efficiency]. AB - Male 21 d-old Wistar rats, were fed for 4 wk with diets containing casein or soybean proteins (10%) with 0.5, 1, 2 or 3% sodium alginate or sodium carrageenan or without any alginate or carrageenan. Daily protein intake and weight gain of casein-fed rats were not significantly different (P less than 0.05) from those of rats fed soybean meal with alginate, whatever the dose received. Rats fed 3% carrageenan in soybean meal had significantly higher feed intake than that of rats fed casein. At the levels studied, alginate had no effect on the Protein Efficiency Ratio (PER), but carrageenan did. The addition of increased quantities of carrageenan to soybean meal followed by heating the mixture led to a progressive and significant decrease in PER at all levels of carrageenan compared to casein feeding. The addition of 3% carrageenan to heated soybean meal, corresponding to 0.62% of meal diet, led to a significant decrease in PER. These results confirm the precipitating role of carrageenans on proteins. PMID- 2244968 TI - Changes in plasma testosterone, thyroxine and triiodothyronine in relation to sperm production and remex moult in domestic ganders. AB - Changes in plasma testosterone (T), thyroxine (T4), triiodothyronine (T3), semen output and remex moult were studied in domestic ganders. A bimodal pattern in both plasma T and sperm concentration was observed during the annual cycle. Ganders started to produce semen at the end of January; maximum semen volume (0.32 +/- 0.04 ml) and sperm concentration (148 +/- 38 x 10(3)/mm3) were reached in March and a marked decrease was observed after mid-April, when the moult of the remiges began. Plasma T3 levels peaked in February (9.7 +/- 0.6 nmol.l-1) and this peak coincided with maximum T concentrations (9.8-10.4 nmol.l-1). Elevated levels of T4 were found from late February until mid-April (31.0-33.6 nmol.l-1). Plasma T concentration was low at all stages of remex moult and regrowth. Decreased T4 levels were found in ganders during remex regrowth from the "brush" to half of the full primary growth stage. Higher plasma T4 levels were found before and after this stage of the moult. A reverse pattern was observed for T3 concentrations. PMID- 2244969 TI - Role of the hippocampus in temporal and spatial navigation: an adaptive neural network. AB - The hippocampus has been proposed to participate in either spatial or temporal mapping. As an alternative to these seemingly conflicting views, we hypothesized that the hippocampus computes 'aggregate predictions' of environmental events that are used to control associative learning. Aggregate predictions forecast what event is going to occur, when in time, and where in space. The hypothesis assumes that activity of hippocampal pyramidal neurons is proportional to the instantaneous value of the aggregate prediction, and that the computation of the aggregate prediction is impaired by hippocampal lesions. In order to test the 'aggregate prediction' hypothesis in both spatial and temporal tasks, this paper presents a real-time neural network capable of describing temporal discrimination and spatial learning in a unified fashion. The neural network incorporates detectors that can be tuned to a particular value of continuous temporal or spatial variables. In the temporal domain, computer simulations were carried out for temporal discrimination in classical conditioning and instrumental learning, classical conditioning under different interstimulus intervals (ISIs), and classical conditioning with mixed ISIs. In the spatial domain, computer simulations were carried out for place and cue learning. The paper shows that under the 'aggregate prediction' hypothesis the network correctly describes activity of hippocampal pyramidal neurons and the effect of hippocampal lesions in temporal and spatial learning. These results suggest that, rather than either a temporal or spatial function, the hippocampus is involved in the computation of variables common to both temporal and spatial navigation. PMID- 2244970 TI - Dynamic properties of human goal-directed arm movements. AB - In the present study, the velocity of pointing movements towards visual targets was analyzed. In accordance with the literature, tangential velocity was found to exhibit rather smooth, single-peaked profiles. In contrast, however, the profiles of the velocity components in the Cartesian coordinates of space were conspicuously multi-peaked, and suggestive of sums of a smooth curve and an oscillation. Oscillation frequency was 4-6 Hz, and its amplitude 200-600 mm/s; the phase shift between horizontal and vertical oscillation was about 180 degrees. The oscillation remained unaltered when the external load of the arm, the size of the visual target, or the required movement direction were changed. The relationship between the present findings and previously documented rhythmic properties of motor control is discussed, and it is concluded that the oscillations may have been generated by neural circuits with inherent oscillatory properties. PMID- 2244971 TI - Neonatal and adult forebrain norepinephrine depletion and the behavioral and cortical thickening effects of enriched/impoverished environment. AB - Two experiments examined the effects of neonatal or adult intracerebral injections of 6-hydroxydopamine (6-OHDA) on the effects of enriched (ENR) vs. impoverished (IMP) housing conditions. In Expt. 1, neonatal rats received intraventricular injections of 6-OHDA after pretreatment with buproprion to destroy norepinephrine (NE) terminals while lessening damage to dopamine (DA) terminals. The rats were subsequently raised in either enriched or impoverished environments and then tested for their spatial problem-solving ability in an automated Hebb-Williams maze. Littermates did not undergo this testing but were instead assessed for cortical thickness. Despite the substantial depletion of NE in the forebrains of the 6-OHDA-treated rats, they responded to enriched rearing as did the control rats, i.e., they solved the Hebb-Williams problems more efficiently than their impoverished reared counterparts and they showed thicker cortices. In Expt. 2, adult rats received 6-OHDA lesions of the dorsal noradrenergic bundle and were then relegated to enriched or impoverished housing for 42 days. Subsequently, the enriched-housed rats solved the Hebb-Williams mazes more efficiently than their impoverished-housed counterparts and this effect of housing was not altered by the dorsal bundle lesion which severely depleted forebrain NE. These two experiments do not support a role for forebrain NE in the alteration of the rat cortex and behavior by environmental enrichment. It was concluded that the cognitive effects of enriched rearing do not require intact forebrain NE but that they may be influenced by the peripheral sympathectomy that is one consequence of neonatal systemic 6-OHDA injections. PMID- 2244972 TI - Visual impairments in macaques following inferior temporal lesions are exacerbated selectively by additional damage to superior temporal sulcus. AB - The present study examined the behavioural effects of removing the inferior temporal cortex (area TE) either on its own or in combination with the adjacent fundus and upper bank of the superior temporal sulcus (area STP). Comparisons with preoperative behaviour showed that the addition of superior temporal sulcal damage led to an increase in visual components of the Kluver-Bucy syndrome, i.e. an increased tendency to touch and examine objects coupled with a decrease in emotional reactivity, but no excessive orality, changes in food preference, or coprophagia. No group differences were found in the learning of 3 pattern discriminations, but the animals with additional superior temporal sulcal lesions were more impaired than the others on 3 colour discriminations, successive reversals of an object discrimination, and a learning-set task. These findings indicate that STP provides an important route, independent of the route via TE, by which visual information can reach limbic structures to evoke affective responses and contribute to visual learning. PMID- 2244973 TI - Dominant mice show much lower concentrations of methionine-enkephalin in brain tissue than subordinates: cause or effect? AB - Possible relationships between dominance rank and brain methionine-enkephalin content were studied by using a method of consecutive rank determination in groups of mice reassembled according to their initial ordinal dominance rank. Thus, 10 groups of 3 Balb/c AnN mice of identical ordinal rank were formed with the consecutive dominants of 3 groups of 10 mice. Dominant, subdominant, subordinate and non-aggressive mice were recognized in these groups. Rank order was strongly correlated with brain Met-enkephalin content. Dominant mice contain less than a fourth Met-enkephalin immunologic reactivity in the brainstem and about half the forebrain concentration than subordinates. Brainstem Met enkephalin correlated with the final ordinal rank and, accordingly, it was found to decrease exponentially after mice acquired alpha-dominance status. Different concentrations in the forebrain correlated with the initial but not the final ordinal rank and, therefore, probably preceded dominance status. PMID- 2244974 TI - Proactive interference effects on short-term memory in rats: I. Basic parameters and drug effects. AB - An operant delayed-matching task was used to assess the role of proactive interference (PI) effects on short-term memory capacity of rats. Task performance was analyzed in terms of the influence of the sample positions and response choices on previous trials. PI was predominantly attributable to the influence of the immediately previous trial but not preceding trials and was abolished by increasing the intertrial intervals from 5 to 15 s. Nicotine induced a decline in choice accuracy only on trials in which the previous response had been to the side opposite the current sample and correct response, suggesting an increased susceptibility to PI. Physostigmine induced a mild, relatively nonspecific decline in response accuracy. Clonidine induced delay-dependent impairments irrespective of responses on previous trials. None of these drugs enhanced choice accuracy at any dose tested. PMID- 2244975 TI - Proactive interference effects on short-term memory in rats: II. Effects in young and aged rats. AB - Whether the short-term memory impairments of aged rats in an operant delayed matching task is attributable to increased susceptibility to proactive interference (PI) was tested. Groups of young and aged rats were trained on the task, and the previously reported delay-dependent deficit of aged rats was replicated. The aged rats showed a significantly greater decline in performance on previous-response-opposite trials compared with previous-response-same trials than did young rats, when tested over the same range of delay intervals, suggesting a higher sensitivity to PI. However, this effect was established against a higher overall baseline performance of the young animals on both types of trial. When the young and aged animals were equated for performance on previous-response-same trials (by increasing the range of delay intervals used for testing the young animals), the interaction effect was abolished. Thus, the delay-dependent deficits of aged rats are independent of their sensitivity to PI. PMID- 2244976 TI - Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus. AB - Rats (n = 11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n = 8) or unoperated (n = 5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions. PMID- 2244977 TI - Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus. AB - Rabbits were first given left cerebellar interpositus nucleus lesions followed by classical nictitating membrane (NM) conditioning using paired presentations of a tone conditioned stimulus and an air puff unconditioned stimulus. Multiple-unit hippocampal activity was monitored over the course of training. In rabbits with anterior interpositus lesions, the acquisition of learned responses and significant increases in training-related hippocampal activity were prevented when paired training was given to the left NM but not when training was switched to the right NM. Rabbits with lesions anterior to the interpositus or in surrounding cerebellar regions failed to show deficits in behavioral responding or hippocampal activity. These results indicate that acquisition of conditioning related activity in the hippocampus depends on an intact interpositus nucleus of the cerebellum. PMID- 2244978 TI - When pentobarbital is the conditioned stimulus and amphetamine is the unconditioned stimulus, conditioning depends on the type of conditioned response. AB - Injections of drugs into rats were used as conditioned stimuli (CSs) and as unconditioned stimuli (USs). With heart rate (HR) conditioning, the pentobarbital CS produces a higher HR than under control conditions. With avfail (aversion failure) conditioning, the pentobarbital CS loses much of its capacity to induce a conditioned taste aversion. HR conditioning was obtained with forward delays of up to 30 min and backward delays of up to 270 min, where the delays are defined by the interinjection interval. Avfail was obtained with forward delays of up to 270 min but not with backward delays. Neither HR conditioning nor avfail were context specific but could be demonstrated in a test apparatus after pairings that occurred in the home cage. This indicated that the external environment was not an important part of the effective stimulus complex. When HR conditioning was obtained, its latency and duration was not related to the delay between the CS and US injections or whether they were forward or backward. PMID- 2244979 TI - Context-specific morphine withdrawal in rats: duration and effects of clonidine. AB - Rats previously injected with morphine in a particular environment (paired rats) emitted more withdrawal symptoms in that environment than did rats previously injected with morphine in another environment (unpaired rats) after both 1 day and 5 days of morphine abstinence. Thus, reexposure to an environment previously associated with morphine can elicit context-specific withdrawal even after several days of morphine abstinence. Clonidine (0.06 mg/kg) reduced most of the withdrawal symptoms seen 5 days after morphine abstinence in both the paired and unpaired rats. However, clonidine enhanced many of the withdrawal symptoms in both groups of rats during naltrexone-precipitated withdrawal 1 day after morphine abstinence. PMID- 2244980 TI - Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats. AB - In 2 experiments, the development of adjuvant arthritis (an experimental autoimmune disease) was inhibited by exposing rats to a flavored solution that had previously been paired with injections of cyclosporine (an immunodepressive drug) compared with rats with the same history but exposed to a flavored solution that had previously not been paired with drug injections. In contrast to earlier experiments on conditioned cyclophosphamide effects, rats did not avoid the taste that had previously been paired with drug administration. Thus, conditioned immunopharmacologic effects were not confounded with taste aversion. These observations are interpreted as reflecting an associative learning process that affected the development of an autoimmune disease. PMID- 2244981 TI - Cue exposure during a period of abstinence reduces the resumption of operant behavior for oral ethanol reinforcement. AB - The present study examined the prediction made by learning theories of drug addiction that systematic cue exposure (extinction) procedures should reduce ethanol (EtOH) consumption. In 3 experiments, male rats were trained on a variable-interval schedule to press a bar for a sweetened EtOH solution. These procedures established associations between a variety of cues (contextual, response feedback, visual, taste) and EtOH consumption. After performance had stabilized, a period of abstinence was imposed during which no EtOH was available. Groups of rats differed only in the number of EtOH-associated cues experienced during this period. The level of EtOH consumption after abstinence was reduced in proportion to the degree of cue exposure. These findings support the learning hypothesis that drug-associated cues contribute to the resumption of drug-taking behavior and further suggest that extinction procedures may be valuable in preventing relapse. PMID- 2244982 TI - Sodium appetite in lactating rats. AB - Lactating rats that were given free access to sodium-deficient food, water, and 0.51 M NaCl solution showed no evidence of sodium appetite. The estimated daily loss of 1-2 mEq Na in milk was replaced by basal daily intake of 2-5 ml of saline. Sodium loss in urine was minimal, but milk sodium concentration was unchanged, and pups grew normally. Saline intake was enhanced when lactating rats that had been maintained on standard laboratory chow were injected with 30% polyethylene glycol solution to reduce plasma volume but no more so than when virgin female rats or male rats were similarly colloid-treated. Lactating rats markedly increased their intake of NaCl solution after simply depriving them of dietary sodium for 4 days, whereas male and virgin female rats did not. These findings indicate that pronounced sodium appetite does not invariably accompany lactation in rats, although it can occur whenever such animals become hypovolemic or sodium deficient. PMID- 2244983 TI - Autonomic origins of cardiac responses to nonsignal stimuli in the rat. AB - Heart rate (HR) and blood pressure responses to nonsignal auditory stimuli were measured in rats after saline or pharmacological blockade of the sympathetic or vagal innervation of the heart. HR responses to the low-intensity stimulus were predominantly deceleratory, whereas responses to the high-intensity stimulus were more notably acceleratory. Both stimuli elicited a biphasic pressor-depressor response, although potential baroreflex influences accounted for only a small proportion of the HR response variance. Deceleratory responses to the low intensity stimulus were eliminated by scopolamine and thus appeared to be predominantly of vagal origin. Acceleratory response to the high-intensity stimulus appeared to be mediated primarily by sympathetic activation because it was substantially attenuated by the beta 1 antagonist atenolol. Furthermore, HR responses to the low-intensity stimulus appeared to reflect coactivation of both sympathetic and vagal systems. PMID- 2244984 TI - Performance on two fixed-interval schedules in the absence of neocortex in rats. AB - Rats with complete surgical removal of the neocortex (neodecorticates) were trained, with milk as the reinforcer, on a 40-s fixed-interval (FI-40) schedule, then on an FI-120, and finally reexposed to the FI-40. Like controls, neodecorticates developed and appropriately adjusted their postreinforcement pauses and response distributions and showed scallop-type responding on the FI 120 and a positive correlation between running rate and the preceding postreinforcement pause on both FI-40 schedules but not on the FI-120. On some variables neodecorticates reached asymptotic levels of performance more slowly than controls. Extended training on the first FI-40 did not differentially affect neodecorticates' performance. The results suggest that neodecorticates retain a functional timing mechanism. PMID- 2244985 TI - Motivational-sensorimotor interaction controls aphagia and exaggerated treading after striatopallidal lesions. AB - This study examined the relationship between sensorimotor and motivational functions of the corpus striatum. In rats, excitotoxic lesions of the corpus striatum (neostriatum and globus pallidus) caused by kainic or quisqualic acid can produce both aversive aphagia and a "choreic" sensorimotor syndrome: an exaggerated treading of the forepaws that is triggered by oral sensory stimulation. Experiment 1 used a recovery-of-function approach to show that (a) aphagia induced by ventroposterior striatopallidal lesions was accompanied by an enhancement of aversion (a specific motivational process) to sweet stimuli, which was expressed in taste reactivity measures of affective evaluation; (b) aphagia and enhanced aversion recovered together; and (c) exaggerated treading did not disappear with aphagia-aversion but narrowed the range of its eliciting trigger to sour and bitter stimuli. Experiment 2 used a partial lesion approach to show that this dissociation of enhanced aversion and exaggerated treading could be reproduced by smaller lesions immediately after striatopallidal damage. Experiment 3 used a conditioned aversion procedure to show that the stimulus for exaggerated treading was aversion (natural or conditioned) and not a simple sensory feature of oral stimulation. Three conclusions were made: (a) Exaggerated treading after a small lesion or after partial recovery from a larger one results from a restructuring of a sensorimotor relations that is nested within a system of aversive reaction, (b) exaggerated treading is elicited only by tastes that elicit natural or conditioned aversion, and (c) more extensive lesions potentiate aversion to tastes that are normally palatable and expand the range of treading elicitors to include those tastes. In other words, affective and sensorimotor systems interact in a hierarchial manner in the production of choreic treading. These results demonstrate a specific hierarchical link between motivational and sensorimotor functions mediated by striatopallidal circuits. PMID- 2244986 TI - Developmental change in unilateral olfactory habituation is mediated by anterior commissure maturation. AB - Habituation of an orienting response in rat pups was used to study the development of the anterior commissure (AC) and its role in olfactory memory. Six and 12-day-old pups received odor presentations to one side of their olfactory system and were tested later for habituation to additional presentations made to either the trained or untrained side. Six-day-old pups remembered only on the trained side. Twelve-day-old pups remembered when tested on either side. Transection of the AC in 12-day-old pups before, but not after, training prevented the transfer of memory. Thus, between 6 and 12 days of age, olfactory cross-projections carried in the AC mature and provide a functional substrate for transfer, at the time of training, of a form of olfactory learning. PMID- 2244987 TI - Ultrasonic vocalizations by rat pups in the cold: an acoustic by-product of laryngeal braking? AB - Isolated rat pups respond to cold exposure physiologically by increasing metabolic heat production and behaviorally by emitting ultrasound. The relationship between these 2 responses was investigated by monitoring oxygen consumption, heat production by brown adipose tissue, respiratory rate, and ultrasound production during cold exposure in pups 10-12 days of age. All 3 physiological measures increased contemporaneously with the initiation of ultrasound. Pups also exhibited a respiratory pattern characterized by the prolongation of expiratory duration in relation to inspiratory duration. Ultrasound was often detected during these prolonged expirations, suggesting that pups were using laryngeal braking. Laryngeal braking is thought to enhance oxygen uptake in the lungs. Thus, ultrasound may be an acoustic by-product of a respiratory maneuver that increases oxygen delivery to metabolically active tissues during cold exposure. PMID- 2244988 TI - Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus. AB - Angiotensin receptors in the most ventral part of the ventral median preoptic nucleus (VVMnPO) or organum vasculosum laminae terminalis appear to be important for salt appetite to angiotensin in rats. If so, then small lesions of this region should reduce salt appetite that is dependent on angiotensin. In separate experiments, the lesion greatly reduced salt appetite after treatments with chronic oral captopril or sodium depletion. On the other hand, the VVMnPO lesion actually enhanced salt appetite to deoxycorticosterone acetate. The lesion did not affect water intake to water deprivation, combined food-water deprivation, isoproterenol, or hypertonic saline, and basal plasma osmolality and sodium values were normal. These experiments suggest that VVMnPO lesions selectively affect angiotensin-induced salt appetite without producing the gross hydrational deficits that occur with larger lesions of the ventral forebrain. PMID- 2244989 TI - Erythropoiesis and erythrocyte age distribution in hemodialysis patients undergoing erythropoietin therapy. AB - Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D50 = 1.0674 +/- 0.0016 g/ml) and in 14 hemodialysis patients (D50 = 1.0674 +/- 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D50 reached a minimum after 2 weeks (D50 = 1.0655 +/- 0.0022 g/ml; p less than 0.05 vs. value before therapy) and a steady state after 4 weeks (D50 = 1.0658 +/- 0.0013 g/ml; p less than 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations greater than 10 pmol/l, a significantly (p less than 0.05) reduced amount of younger RBCs (D50 = 1.0675 +/- 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH less than 10 pmol/l (D50 = 1.0677 +/- 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount. PMID- 2244990 TI - Paired filtration dialysis: studies on efficiency, flow dynamics and hydraulic properties of the system. AB - Several strategies have been proposed to increase dialysis efficiency in order to reduce dialysis treatment time. Paired filtration dialysis (two-chamber technique) is a new technique combining the advantages of highly permeable membranes and convective transport with the high depurative efficacy of diffusion. The system operates with two units in series (hemofilter + dialyzer) with membranes of polysulfone and hemophan, respectively. A detailed analysis of the hydraulic properties of the system and its possible optimization in terms of depurative efficiency is reported in this paper. In vitro and in vivo tests provided data sufficient to draw some hypotheses on a new utilization of the system. The system appears to be adequate for operating under conditions of high blood flows, however, some limitations were evidenced during our evaluation: the convective component may be insufficient and further increases are impossible because of the limiting effect of the low surface area of the hemofilter; the configuration in which the weight loss is achieved in the hemofilter exposes to the risk of backfiltration in the dialyzer, reducing the benefits of a highly biocompatible system, and the use of acetate in the dialysate and/or lactate in the substitution fluid may interfere with a satisfactory correction of metabolic acidosis. On the basis of our evaluations, some changes can be proposed such as: (1) increased surface area of the hemofilter; (2) use of blood flows higher than 300 ml/min; (3) use of bicarbonate in the dialysate and in the replacement solution; (4) increased convective component with ultrafiltration rates of 50-60 ml/min and full replacement with substitution fluid in between the two filters, and (5) weight loss achieved in the dialyzer with a constantly positive transmembrane pressure. With such a modification of the operative conditions, paired filtration dialysis can be probably applied as a highly efficient dialysis technique in a large number of patients with a significant reduction of dialysis treatment time. PMID- 2244991 TI - Correlation between blood prostaglandins, plasma lipids and atherosclerosis in dialyzed patients. AB - The correlations between the degree of atherosclerosis, plasma prostaglandins (PGs) and plasma lipids were examined in maintenance hemodialyzed patients with and without diabetes mellitus. The degree of atherosclerosis was evaluated by pulse wave velocity (PWV) of the aorta. Plasma PGs were radioimmunoassayed. PWV was significantly higher in hemodialyzed patients compared to sex- and age matched healthy controls. PWV correlated with the plasma thromboxane A2 (TXB2) level and TXB2/6-keto-PGF1 alpha ratio in hemodialyzed patients, without a significant difference between the diabetic and nondiabetic groups. The plasma lipid profile was type IV of the WHO classification in both the diabetic and nondiabetic groups, and PWV did not correlate with these lipid abnormalities. Though not significantly, the decreases in plasma PGE2 and 6-keto-PGF1 alpha and the increase in TXB2 correlated with the degree of type IV hyperlipidemia. The results suggest that plasma PG abnormalities might correlate with the degree of atherosclerosis in hemodialyzed patients. PMID- 2244992 TI - Solute transport in continuous arteriovenous hemodiafiltration: a new mathematical model applied to clinical data. AB - A mathematical model of continuous arteriovenous hemodiafiltration is presented, by which the diffusive mass transfer coefficient (Kd) for a solute may be calculated from blood, filtrate and dialysate flow rates and solute concentrations. The model was applied to clinical data obtained with 0.6-m2 AN69 capillary dialyzers that had been used for up to 5 days. The diffusive mass transfer coefficient proved to depend on dialysate flow rate. Furthermore, it was related to the membrane index of ultrafiltration, as measured in the clinic, and to the filter resistance to blood flow. Measurement of these filter characteristics allowed a reasonable prediction of solute clearance. PMID- 2244993 TI - Clinical and microbiological evaluation of a postdilutional hemofiltration system with in-line production of substitution fluid. AB - Safety and efficacy of a recently developed hemofiltration (HF) system with in line production of substitution fluid (GHS-10; Gambro, Lund, Sweden) based on a sterilizing filtration of acetate buffered dialysate has been evaluated in 4 patients over a 6-month period. Two patients were prematurely excluded from the study: 1 because of acetate intolerance and the other because of kidney transplantation. Two patients completed the study (240 HF sessions). Treatment adequacy was maintained in the 2 medium term treated patients according to the usual clinical and biochemical criteria and a mean exchange volume of 100-105 liters/week (30-35 liters/session three times weekly). Urea kinetic modeling analysis performed over all HF cycles gave the following results: dialysis index (urea clearance.time-on HF/urea volume space) (KT/V) approximately 1-1.1, urea time averaged concentration (UREA TAC) approximately 15-20 mmol/l, and protein catabolic rate (PCR) approximately 1.1-1.2 g/kg/day. Rare clinical adverse symptoms observed during the course of sessions were attributed to acetate intolerance. Microbiological safety was confirmed in vivo by the absence of pyrogenic reactions after 240 HF sessions (approximately 7 m3 substitution fluid infused intravenously) and in vitro by the constant absence of bacteria and/or endotoxin content limulus amaebocyte lysate (LAL) sensibility threshold 10 pg/l within the infusate produced during the sham HF sessions. The fluid mass balance obtained with the GHS-10 monitor was excellent. The electrolyte composition as judged by Na variation remained in a range of 2-3%. GHS-10 used in this study for postdilutional HF confirms that a large quantity of intravenous quality fluid may be safely produced by ultrafiltration from dialysate. It also introduced a new dimension in biocompatibility of dialysis by demonstrating that sterile dialysate may be routinely produced and used for routine dialysis. PMID- 2244994 TI - Near-patient potassium and sodium measurements: evaluation of ion-selective electrodes (Ionometer EF2) in a dialysis department. AB - For potassium and sodium monitoring, an Ionometer EF2 was installed in our dialysis unit. The apparatus measured linearly, and between-series and within series variations were comparable to flame photometry. No difference in performance was disclosed when operated by one or several persons. The 95% limits of agreement between Ionometer EF2 and flame photometry were for potassium -0.29 and 0.43 mmol/l and for sodium -5.0 and 2.89 mmol/l, respectively. Contrary to sodium, the accidental difference for potassium was greater than expected from analytical variation. PMID- 2244995 TI - [Blood alcohol value and responsibility in the jurisdiction of the German Federal Court]. AB - The author shows, what effect as a circumstantial evidence the ascertained or the possible blood alcohol concentration has in the jurisdiction of the Federal Court as far as the responsibility is to be judged on. He thinks, that the dispute, which seemed to be at hand between the decisions of the 1. and 4. penal senate, is not to be noticed. According to his opinion the blood alcohol concentration has an outstanding importance for the jurisdiction on the responsibility. PMID- 2244996 TI - [Forensic value of analytic results from less than 5 (4) blood alcohol values of a blood sample]. AB - 1. If the material for blood-alcohol examinations is insufficient under the existing regulations (specification in the GUTACHTEN DES BUNDESGESUNDHEITSAMTES) it is possible to determine the mean value almost certainly, estimating the confidence-interval. This mean value can be taken as basis of the opinion with regard to safe driving. 2. The proposed statistical procedure is described and compared with other suggested calculations. 3. Testing the proposed procedure by means of 1,426 real data, the usefulness of the proposed calculation is shown. PMID- 2244997 TI - [Midazolam--a forensic problem drug?]. AB - Benzodiazepine derivates can cause transient global amnesia even when administered in therapeutical doses. As amnesia seems to be more frequent than supposed, it is relevant for traffic medicine. We shall discuss forensic cases in which Midazolam amnesia was suspected with special attention to the interpretation of toxicological data. PMID- 2244998 TI - [Experience after one year's computer-assisted determination and evaluation at the alcohol dehydrogenase laboratory]. AB - The processing of blood alcohol measurements by alcohol dehydrogenase method (ADH) was improved by using a tailored software program. The program is written in Turbo BASIC and requires an IBM Personal Computer (PC/XT/AT) or compatible with at least 640K memory and a graphic adapter (EGA or Hercules). All features of the program are available from the menu bar with pull down menus. The program stores on disk or harddisk the optical density values measured with an HITACHI spectrophotometer. After the measurement the calculation of alcohol concentration is accomplished by the program. The results can be transferred and further handled with database systems (e.g. DBASE III). Stored values are used to calculate the reproducibility of calibration and the precision of single determinations. PMID- 2244999 TI - [Driver's license and driving fitness after introduction of driver's permit on probation. Considerations and arguments in traffic psychology]. AB - The discussion on topics like post-schooling and rehabilitation of motorists has intensified the contacts between advocates of traffic law and traffic psychologists in the last years. Since the driver's licence on probation has been introduced, the points of contact between driving licence law and theory of driver's qualification have become more distinctly visible. In the legal institution of driver's licence on probation the driving licence law relies on the changeability of the driving beginner by means of post-schooling. This continues the development of the legal aim of improvement besides the prevention. The concept of "changeability" has entered into the expert opinion on driver's qualification since the middle of the 1970's and it has been tested in the psychological rehabilitation of motorists. It is widely realized, that the inherited idea of 'character' is not useful for a flexible guaranty of traffic safety by an administrative authority. The driving qualification rather has to be seen as a biographical quantity. Motorists are submitted to a change of experience. Among conspicuous drivers the risk of a renewed conspicuousness is in the centre of view. There are possibilities of influence on this risk with some measures. The author shows the basis and the consequences of this concept of a biographical qualification. It bases on the concept of a driver, who is able to learn and is self-responsible and who needs specific back-channel informations. But the author also shows the limits of changeability of a motor-driver. PMID- 2245000 TI - Female DWI-delinquency and chronic alcoholism in Dusseldorf. AB - The blood sample records of all 1,231 blood samples of female DWI-offenders submitted to the Dusseldorf Institute of Forensic Medicine in 1986/87 were analysed for date and time arrest, age, additional drug intake. BAC and results of medical examination. The data obtained were compared to a randomly selected male comparison group and to the situation in the sixties. The proportion of women arrested for impaired driving has increased from 1.75% in the sixties to 7.5% in 1986/87 (factor 4.3), the percentage of highly intoxicated women (BAC above 2.5 g/l) from 0.07% to 0.55% (factor 7.9). Current female DWI behavior is quite similar to male with both groups mainly comprising highly intoxicated young subjects apprehended on the days of the weekend in the hours around midnight. Women more often admit additional drug intake with benzodiazepine abuse representing a major problem. As concluded from time of arrest, discrepancy between BAC and degree of drunkeness and blood methanol levels about 60% of the women with a BAC above 2.5 g/l have to be classified as chronic alcoholics. As a consequence female alcoholics are significantly overrepresented in female DWI delinquency. PMID- 2245001 TI - Water treatment systems for pharmaceutical purposes. AB - Water is the key component in pharmaceutical production and in related activities. Different types of water having different standards are used in pharmaceutical production plants. An accurate definition of the uses, of the chemical-physical and microbiological specifications, of sampling and testing programs is needed for the correct design and management of water production and distribution systems. The types of water taken into consideration are purified water and water for injection, being the most critical ones. The water production systems are described analog with the principles of function and the instrumental controls specifying the key features which guarantee the high standards of chemical-physical and biological quality of the water produced. A trouble-free use of water in the plant is related to the holding and distribution system. An overview view of the design criteria and management of such system is considered. Description of the aspects regarding the validation and monitoring of water treatment systems is given. PMID- 2245002 TI - [The international system of drug control]. AB - The ADR reporting systems applied worldwide, which are most commonly known and can be taken as an example, are described as a general overview. More precisely, the descriptions refer to: "Voluntary Reporting System" and "Prescription Event Monitoring"--UK; FDA regulations and "Boston Collaborative Drug Surveillance Program"--USA; "Centre Regional de Pharmacovigilance"--France. The experience in the North Countries and Japan is also briefly illustrated. Furthermore, initiatives taken by the Council of International Organizations of Medical Science (CIOMS) and by the WHO are mentioned. This short overview highlights that the Health Authorities in the most advanced Countries have shown an ever growing attention for ADR reporting, and the regulations in every Country take into special consideration the serious and the unforeseen adverse reactions, as well as their recurrence. PMID- 2245003 TI - [Thermoanalytic techniques for the study of pharmaceutical products]. AB - During the past years, there have been frequent demonstrations that thermoanalytical methods have found wide-spread use in pharmacy. Analysts have developed these techniques in pharmaceutical field in the estimation of impurities, in quality control procedures, in preformulation studies, in the active principle identification, in accelerated stability and in production process optimization. Wide-spread use of thermal methods is devoted to the identification of solid state of drugs (polymorphism, solvate, inclusion compound,...) due to its possible implication on bioavailability or on the stability of a final dosage form. Some examples of thermoanalytical applications are reported. PMID- 2245004 TI - Preformulation studies on suppositories by thermal methods. AB - The application of differential scanning calorimetry (DSC) is described for investigating the interaction between trimethoprim and sulfamethoxypyridazine in suppository formulations containing fat bases (Suppocire, Novata, Witepsol). The thermal behavior of suppositories at various storage times is deeply influenced by the fat base and by interaction between active ingredients. Liquefaction time and dropping temperature were also evaluated for comparison and control purposes. PMID- 2245005 TI - Misleading results in studying pharmacodynamic interaction with oral anticoagulants. AB - An experimental conditions is described in which the i.p. administration to rats of irritants produces a misleading increase of the anticoagulant effect of warfarin. Groups of 10 adult Wistar rats were treated i.p. or i.v. with HCl 0.1N plus warfarin p.o.; 24 hr after warfarin administration, prothrombin time was determined on citrate blood specimens and the animals were submitted to autopsy. When HCl is given i.p., a significant increase of prothrombin time is observed. On the contrary following i.v. administration no interference with the anticoagulant effect of warfarin is observed. Abdomen exploration of rats shows the presence of serum exudate following i.p. but not i.v. administration of HCl. The synergistic effect of i.p. administration of HCl on anticoagulant effect of warfarin appears an experimental artifact, probably attributable to a non specific local irritating effect. This result stresses the need of caution in interpreting animal data indicating a synergism with oral anticoagulants. PMID- 2245006 TI - [ATC classification: lights and shadows]. AB - The issue draws the story of ATC classification which, risen from the need to study drug consumption in different countries, is extending towards the regulatory area. The features of ATC classification which get it superior to the classification used by different pharmaceutical european data sheet compendia, are the introduction of an anatomical level and study of the criteria used for the definition of levels (ATC guidelines). However some important problems are still open, which suggest great attention in the application of ATC system to regulatory area. Finally, it is underlined the necessity to modify continuously the ATC system on time with the development of scientific acquisition. PMID- 2245007 TI - Laminin in testicular germ cell tumours. An immunohistochemical study. AB - Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis. PMID- 2245008 TI - Neutrophil chemotactic activity of peptidoglycan. A comparison between Staphylococcus aureus and Staphylococcus epidermidis. AB - The ability of peptidoglycan from Staphylococcus epidermidis and Staphylococcus aureus to generate in human serum chemoattractant for peripheral blood neutrophils was studied. It was shown that PG from the two bacteria was able to induce chemotactic activity in normal human serum. Sonication of PG was required to generate this activity. Very little or no activity was generated in heat treated or C5-deficient human serum by PG, indicating that PG treatment of serum resulted in generation of chemoattractants by activation of complement. Kinetics studies employing C2-deficient or MgEGTA-chelated serum revealed that S. epidermidis induced chemotactic activity by activating the alternative complement pathway. The alternative complement activation induced by S. epidermidis occurred rapidly and was completed after 15 min, whereas S. aureus activated the alternative pathway much more slowly, with activation reaching a maximum at 60 min. The rapid activation of the alternative complement pathway by S. epidermidis PG may partly explain why this bacterium does not normally cause infections in healthy individuals. PMID- 2245009 TI - Effect of polyoxyethylene sorbate compounds (Tweens) on colonial morphology, growth, and ultrastructure of Mycobacterium paratuberculosis. AB - Polyoxyethylene sorbate (Tween) compounds were tested to compare their growth stimulation effects on Mycobacterium paratuberculosis. Three low passage and three high passage clinical isolates and ATCC strain 19698 were used. Tween 20, 40, 60, and 80 were tested at concentrations of 0, 0.001, 0.01, 1.0, and 3.0% (w/v) in radiometric broth culture media and in Middlebrook 7H9 agar plates. Scanning and transmission electron microscopy were used to examine cell wall appearance and ultrastructure, respectively. In broth culture, 0.1% (w/v) Tween 60 most dramatically enhanced growth of M. paratuberculosis ATCC strain 19698. The effects of Tween 40 and 80 on growth took a bimodal form, enhancing growth at concentration ranges of 0-0.01% and 0.1-1.0% (w/v) but suppressing growth at concentrations of 0.01-0.1% (w/v). Two of three high passage clinical isolates grew optimally in the presence of 1.0% (w/v) Tween 80, while the remaining high passage isolate and all three low passage isolates grew best in media containing 0.1% (w/v) Tween 80. Colonial morphology of all strains grown on Middlebrook 7H9 agar without Tween 80 was irregular and granular whereas colonies on plate media containing greater than 0.01% (w/v) Tween 80 were entire, smooth, and domed. Scanning electron microscopy also revealed a transition from rough to smooth cell walls with increasing Tween 80 concentration. Transmission electron microscopy showed the presence of low electron dense intracellular vacuoles in Tween 80 grown M. paratuberculosis cells. Thus, Tweens altered colonial morphology, the cell wall surface, and ultrastructure of M. paratuberculosis and stimulated its growth in vitro in a concentration-dependent, and often bimodal, fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245010 TI - Estrogen and progesterone receptors in epithelial ovarian tumours. AB - A study of the estrogen receptor (ER) and progesterone receptor (PR) status and content in 43 patients with histologically proven primary epithelial ovarian tumours was undertaken. The results of ER and PR status in 604 primary epithelial ovarian carcinomas of different histological types were analyzed in a combined material collected from the literature (576 cases) and 28 cases from our own study. Statistical analysis showed significant difference in ER status, but not in PR status, between the different histological types. The highest proportion of ER positive tumours was found among the serous and endometrioid types. Thus when analysing the correlation of ER status with other parameters in ovarian cancer, histological type should be taken into account. In 3 benign, 4 borderline and 14 malignant serous ovarian tumours no statistically significant difference was found in steroid receptor content and status. In 11 patients with multiple tumour locations, only two patients with mixed serous/endometrioid malignant tumours had different receptor status in different tumour locations. PMID- 2245011 TI - The prognostic importance of syncytial growth pattern in medullary carcinoma of the breast. AB - The histopathological criteria for medullary carcinoma of the breast (MC) used by most pathologists today were delineated by Ridolfi et al. in 1977. The prime criterion is: "A predominantly syncytial growth pattern", predominantly being defined as including 75% or more of the tumour. However, no indication has been given as to why this limit was set at 75%. The present study analyzes the prognostic importance of the extent of syncytial growth in a population of 102 breast cancers with medullary features. Generally, we find a positive prognostic influence of an extensive syncytial growth. The prognostic importance of setting the limit for predominantly syncytial growth at 90% and at 75%, respectively, is evaluated. This comparative study provides no basis for changing the definition of predominantly syncytial growth pattern. PMID- 2245012 TI - The influence of properties encoded by the Yersinia virulence plasmid on adhesion of Yersinia enterocolitica to ileal brush border membrane vesicles. AB - The influence of plasmid-associated cell surface structures on the ability of Yersinia enterocolitica to bind to ileal brush border membrane vesicles (BBVs) was investigated. Rabbit or human BBVs were immobilized on polystyrene microtiter plates and adhesion of radiolabeled cells of Y. enterocolitica was determined. Strains of pathogenic serotypes carrying the Yersinia virulence plasmid (pYV+), as well as their isogenic plasmid cured derivatives (pYV-), adhered to immobilized BBVs, but adhesion of pYV+ organisms was markedly greater than that of pYV- ones. Strains belonging to non-pathogenic serotypes did not adhere significantly. The pYV+ strain Ye0301P+ did not express specific adhesion to glycolipids, nor was adhesion to BBVs reduced in the presence of various monosaccharides. Proteolytic digestion of surface structures on strain Ye0301P+ markedly reduced adhesion. pYV+ strains also demonstrated greater adhesion to a non-biological surface (polystyrene) and showed a higher degree of hydrophobicity than pYV- organisms as evaluated in a two-phase partitioning system. It is therefore likely that the plasmid-associated adhesion of Y. enterocolitica is promoted by one or more outer membrane proteins, that confer hydrophobicity to the bacterial surface. PMID- 2245013 TI - Mapping of the rat mast cell granule proteinases RMCPI and II by enzyme-linked immunosorbent assay and paired immunofluorescence. AB - The distribution of the rat mast cell granule proteinases, rat mast cell proteinase I and II (RMCPI and II respectively) has been determined in rat tissues with the aid of highly sensitive and specific enzyme-linked immunosorbent assays (ELISA) and paired immunofluorescence. The major source of RMCPII is the gastrointestinal tract, although low concentrations were also detected in non mucosal sites including thymus, mesenteric lymph nodes, liver, bone marrow, heart, kidney and spleen. Cellular localization by paired immunofluorescence showed that most cells contained either RMCPI or RMCPII, although a minor subpopulation in which individual cells contained both proteinases was also identified in a few tissues. RMCPII-containing cells predominated at mucosal surfaces but were also found in non-mucosal tissues. Individual cells expressing both RMCPI and II were present in lung, liver mesenteric lymph node and submucosa of stomach and were occasionally represented amongst serosal cells from the peritoneal cavity. Connective tissue mast cells of skin and tongue were identified as major sources of RMCPI, although this proteinase was widely distributed in all tissues examined. The present study demonstrates the heterogeneity of mast cell proteinase phenotypes in the rat and emphasises the difficulties in determining mast cell subtypes on tissue location alone. PMID- 2245014 TI - Establishment and characterization of six human melanoma xenograft lines. AB - Six new human melanoma xenograft lines differing considerably in biological properties were established in athymic nude mice and characterized with respect to growth in vivo. Mean volume-doubling time ranged from 1.8 to 17.7 days, mean necrotic fraction from 7 to 39%, and mean fraction of cells in S from 11 to 31% at a tumor volume of 500 mm3. DNA-index and median chromosome number were in the ranges 1.15-1.76 and 46-80, respectively. The lines were all highly malignant by histopathological criteria, but showed significant differences with respect to cell type, cellular pleomorphism, nuclear atypia, nucleolar prominence, and mitotic activity. Several biological characteristics of the donor patients' melanomas were retained in the xenograft lines. All lines showed a human karyotype and the histological appearance was very similar to that of the source tumor material. The distribution of cells in the cell cycle was comparable to that reported for melanomas in man. The six melanoma xenograft lines constitute a tumor panel that shows great promise for future studies of the biology and treatment sensitivity of malignant melanoma. PMID- 2245015 TI - The relationship between left atrial pressure and atrial receptor discharge in dogs and cats with different body weights. AB - The diuretic response to distension of a large balloon in the left atrium and the increase in discharge of atrial receptors for a given increment in left atrial pressure have been found to be greater in dogs with a high blood volume than in dogs with a low blood volume. To determine whether atrial size may influence atrial receptor discharge, a group of cats and two groups of dogs with different body weights were examined under anaesthesia with alpha-chloralose. The relationship between atrial receptor discharge and left atrial pressure was determined in twenty-six fibres from seven cats, thirty-seven fibres from eight small dogs weighing less than 15 kg and twenty-five fibres from five large dogs weighing more than 25 kg. The slope of the relationship between the increase in atrial receptor activity and increments in left atrial pressure was shown to be significantly greater in the large dogs than in the small dogs, and the slopes in dogs were greater than in cats. The size of the atria was greater in larger dogs than small, and both those groups had atria larger than those of the cats. These findings indicate that the response of an increase in atrial receptor discharge to the same increment in left atrial pressure was greater in large animals than small and that this difference is possibly due to the different atrial size. PMID- 2245016 TI - Behavioural thermoregulation in mice: effects of low doses of general anaesthetics of different potency. AB - Chloroform, monochlorodifluoromethane and nitrous oxide produced dose-related decreases in the rectal temperatures of mice allowed to choose between a warm and a cool environment. The doses used were subanaesthetic, respectively 0.0013 0.004, 0.028-0.085 and 0.25-0.5 atm. The hypothermia (up to 3.6 degrees C) was usually associated with significant reductions in time spent in the warm. The log dose-hypothermic response plots were approximately parallel and there was a marked correlation between anaesthetic potency, as measured by the abolition of the righting response, and hypothermic potency. PMID- 2245017 TI - Plasma noradrenaline levels and thermogenic responses to injected noradrenaline in the conscious rat. AB - The changes in metabolic rate (MR) and plasma noradrenaline (NA) were studied in rats injected with NA either subcutaneously (S.C.) or intravenously (I.V.). Injection of NA (400 micrograms kg-1 S.C.) raised the MR by 54.0 +/- 10.2% above baseline and the levels of plasma NA were higher in right atrial venous plasma (147.0 +/- 6.6 nmol l-1) than in arterial plasma (54.4 +/- 6.6 nmol l-1) 90 min after the injection. There was no significant increase in MR in response to the infusion of 0.4 microgram NA min-1 kg-1 but significant responses occurred (P less than 0.01) with infusion of 1.5, 3.0, 4.0 and 8.0 micrograms min-1 kg-1. The maximum increase in MR was 90.3 +/- 7.4% during the 3.0 micrograms min-1 kg-1 infusion. The arterial plasma NA levels were directly proportional to the NA infusion rate, 18.0 +/- 8.3, 72.4 +/- 14.3, 159.5 +/- 28.4, 222.3 +/- 62.1 and 590.0 +/- 172.1 nmol l-1 for the 0.4, 1.5, 3.0, 4.0 and 8.0 micrograms min-1 kg-1 infusion respectively. This study shows that high plasma levels of NA are needed to induce thermogenesis when NA is administered either S.C. or I.V. PMID- 2245018 TI - The effects of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland. AB - The changes in cytoplasmic free calcium ([Ca2+]i) which occur in isolated human sweat glands during cholinergic stimulation have been studied indirectly by monitoring potassium permeability. The acetylcholine-evoked permeability increase normally consists of transient and sustained phases which are attributed to the mobilization of intracellular calcium stores and to calcium influx respectively. Such consistent responses to acetylcholine could not be obtained during superfusion with bicarbonate-free, HEPES-buffered solutions. The human sweat gland in vitro therefore appears to have a strict requirement for bicarbonate. The sustained component of the response was not affected by total removal of external sodium, suggesting that calcium influx does not occur via a sodium dependent system. The transient component, however, was abolished when external sodium was replaced by N-methyl-D-glucammonium (NMDG+). It therefore appears that secretagogue-evoked mobilization of cytoplasmic calcium is dependent, in some way, upon external sodium. This dependence is not, however, absolute as the response was essentially normal when sodium was replaced by lithium. PMID- 2245019 TI - The effect of a hindgut fermentation on urea metabolism in sheep nourished by intragastric infusion. AB - Four female sheep nourished wholly by infusions of volatile fatty acids, buffer and minerals into the rumen and casein into the abomasum were given, in addition, infusions of fermentable carbohydrates into the terminal ileum. The ileal infusions consisted of (1) water alone, (2) 25 g starch + 50 g cellulose, and (3) 50 g starch + 50 g cellulose. Measurement of nutrient digestibility and nitrogen retention were made over 5 days and the kinetics of urea metabolism were measured over 24 h by means of a single injection of [14C]urea. Endogenous urinary nitrogen excretion was measured over a subsequent 5 days when casein was omitted from the infusion mixtures. Increases in hindgut fermentation resulted in a significant increase in faecal nitrogen excretion (P less than 0.01) and a corresponding reduction in urinary urea nitrogen excretion (P less than 0.05). The ileal infusions did not significantly affect urea irreversible loss rate or urea pool size and were also without effect on plasma urea or rumen ammonia concentrations. Urea degradation in the gastrointestinal tract increased by about 2 g/day in progressing from lowest to highest level of hindgut infusion but differences between treatments were not statistically significant. Endogenous urinary nitrogen excretion was not affected by hindgut fermentation and averaged 206 mg N/(kg0.75 day) over the three treatment groups. Faecal nitrogen excretion however increased progressively with increase in ileal infusions (P less than 0.05) and was similar to that seen when nitrogen input was adequate. It is concluded that changes in hindgut fermentation can alter the partition of nitrogen excretion between faeces and urine but the quantities involved are small relative to the total exchange of urea across the digestive tract. The rumen appears to be an important site of urea degradation even when microbial fermentation is absent. PMID- 2245020 TI - The effect of surgical anaesthesia on antral motility in the ferret. AB - Gastric motility was recorded from ferrets chronically prepared with an antral strain gauge. In fasted animals, antral motility showed cycles of activity and quiescence typical of the migrating motor complex (MMC) with a period of 44.7 +/- 6.1 min (n = 4). Anaesthesia with pentobarbitone sodium (50 mg/kg) disrupted this interdigestive motor pattern which returned along with recovery from anaesthesia. The first cycle of antral motility occurred 119 +/- 23.9 min after the onset of anaesthesia and thereafter continued to cycle at the pre-anaesthetic interval. The recovery was unaffected by treatment with guanethidine (2 mg/kg) or naloxone (1.25 mg/kg) but all motility was prevented with atropine (100 micrograms/kg). Following chronic truncal vagotomy cycles of antral activity persisted during pentobarbitone anaesthesia. With prolonged anaesthesia with ethyl carbamate (1300 mg/kg) there was no return to antral cycling but instead continuous low amplitude regular contractions were present. The lack of MMC activity in acute experiments is thus a consequence of the anaesthesia and not the surgical interventions. PMID- 2245021 TI - The effect on intestinal disaccharidase activity of feeding galactose to growing rats. AB - The effect of supplementation of the diet with galactose on the age-related decline of intestinal lactase activity was investigated in 108 growing rats. Starting from 14 days of age, the rats were divided into two groups and fed with chow, and with fluid either as tap water or 5% galactose solution. At 14 days the specific lactase activity was 112.8 +/- 3.2 mumol min-1 (g protein)-1, which decreased to less than 10% of this value at maturity. Galactose supplementation did not prevent the decline. The increase of maltase, sucrase and trehalase was also unaffected. The result suggests that galactose plays no significant role in the regulation of disaccharidase activities in the rat. PMID- 2245022 TI - Histidine-stimulated acid secretion in the conscious rat is mediated by amino acid uptake system N. AB - The characteristics of sodium-dependent, histidine-stimulated gastric acid secretion were studied in the conscious gastric-fistulated rat. Intragastric L histidine, but not glutamine, asparagine, glutamic acid or glycine, stimulated acid secretion. The histidine-stimulated acid secretion was inhibited by the presence of glutamine or asparagine, but not by glutamic acid or glycine. The substitution of lithium for sodium in the gastric perfusate was tolerated. Together with previous data, the results indicate that an N-like amino acid uptake system mediates histidine-stimulated acid secretion in the conscious rat. PMID- 2245023 TI - Separation of tubular electrical activity in amphibian skeletal muscle through temperature change. AB - The effect of temperature on the form of the propagated action potential was investigated in frog skeletal muscle fibres. Increasing the temperature decreased the duration of the initial overshoot but a hump then appeared during a more prominent after-depolarization. Finally, at 28-30 degrees C, the after depolarization was either noticeably enlarged or entirely absent. This all-or none failure of tubular conduction suggests that excitation of the tubular membrane takes place through regenerative activity rather than graded electrotonic spread of depolarization. However, it is consistent with a partial electrical isolation of the tubular lumina, possibly through the access resistance proposed in earlier theoretical models for muscle membrane. PMID- 2245024 TI - Coronary myogenic responses to abrupt changes in aortic blood pressure in anaesthetized dogs. AB - A transient increase in coronary transmural pressure was produced in anaesthetized dogs by occlusion of the descending thoracic aorta. Aortic blood pressure (ABP), left ventricular pressure and coronary flow were measured; coronary vascular resistance (CVR) was calculated. Results were similar in innervated and denervated hearts. Occlusion for 10 and 20 s resulted in no change in CVR for 15 s, followed by a metabolic dilatation attributable to enhanced oxygen demand; after release the fall in ABP resulted in an immediate increase in CVR, caused by vascular elastic recoil, followed by hyperaemia. PMID- 2245025 TI - Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I. AB - The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I. PMID- 2245026 TI - Development of chronic secondary epileptic foci following intrahippocampal injection of tetanus toxin in the rat. AB - It is known that injecting a minute dose of tetanus toxin into rat hippocampus leads to a chronic epileptic syndrome. Here we describe the development of secondary, 'mirror' epileptic foci in the hippocampus contralateral to a single injection of the toxin (12 mouse LD50). This was detected in slices in vitro prepared 6 to 56 days after injection, both as evoked after-discharges and as spontaneous synchronous bursts that were mainly restricted to subregions CA3b and c. PMID- 2245027 TI - Growing interest in transesophageal echocardiography. PMID- 2245028 TI - Biplane transesophageal echocardiography: technique, image orientation, and preliminary experience in 131 patients. AB - Transesophageal echocardiography with use of a uniplane phased-array transducer with a transverse or horizontal scanning plane has become a well-established tool for evaluating cardiovascular diseases. Recent introduction of biplane probes has enhanced the diagnostic capability of this imaging technique. This article discusses the technique of biplane transesophageal echocardiographic examination and image orientation. The diagnostic value and advantages of various biplane transesophageal images of the heart, aorta, and aortic arch from various esophageal positions are described. PMID- 2245029 TI - Transesophageal echocardiography in the diagnosis of ostial left coronary artery stenosis. AB - The diagnosis of ostial stenosis of the left main coronary artery is usually made by use of coronary angiography. However, positioning of the catheter across the obstruction may obscure this diagnosis during contrast injection. Although a damping of arterial pressure when the catheter enters the left coronary artery may suggest ostial stenosis, it may not be possible to make this diagnosis with certainty during cardiac catheterization. We report a series of four patients in whom the left coronary ostium and proximal left coronary arteries were visualized by means of transesophageal echocardiography. Both ostial narrowing by plaque and abnormally fast flow velocities were seen. In each case the echocardiographic findings contributed to the subsequent management of the patients. PMID- 2245030 TI - Transesophageal echocardiographic assessment of systolic and diastolic dysfunction during percutaneous transluminal coronary angioplasty. AB - Left ventricular short-axis cross-sections at the level of the papillary muscles and transmitral flow were obtained with transesophageal echocardiography during percutaneous transluminal coronary angioplasty (PTCA) in 15 patients who had received anesthesia and who all demonstrated new areas of or more severe wall motion abnormality 10.2 +/- 4.3 seconds after initiation of balloon inflation. Both systolic (percentage area reduction and ejection fraction of the ischemic segment) and diastolic (early to atrial peak flow ratio and time velocity integral) function parameters and end-systolic wall stress changed significantly during PTCA. These changes were most profound during PTCA of the left anterior descending artery than they were during PTCA of the right coronary artery. Systolic and diastolic dysfunction are therefore invariably linked during transient ischemia, and PTCA of the left anterior descending artery consistently produced more profound dysfunction. PMID- 2245031 TI - Transesophageal echocardiography during percutaneous balloon mitral valvuloplasty. AB - To ascertain the value of transesophageal echocardiography during percutaneous balloon mitral valvuloplasty, the present study was undertaken in 26 anesthesized patients (21 women and 5 men; mean age, 47 years) with symptomatic rheumatic mitral valve stenosis. In all but one patient the balloon dilation of the mitral valve was successful and Doppler-derived valve area increased (0.9 +/- 0.3 to 1.9 +/- 0.4 cm2). Transesophageal echocardiography provides continuous monitoring, as well as guidance of the procedure. Crossing the arterial septum, as well as delivery of the sheath through the mitral valve orifice and correct positioning of the balloon, was highly facilitated and reduced x-ray exposure time. The degree of mitral regurgitation and the presence of interatrial shunting at the end of the procedure could be readily assessed, making cineangiography not necessary. Complications of the procedure, such as pericardial effusion, could be detected before hemodynamic deterioration had occurred (one patient). The advantages of transesophageal echocardiography for routine monitoring of percutaneous mitral valvuloplasty, however, should be weighted against the added risk and expense of this support. PMID- 2245032 TI - Intraoperative transesophageal versus epicardial ultrasound in surgery for congenital heart disease. AB - Twenty-eight patients (age range, 0.7 to 65 years; median age, 6.1 years) who were undergoing correction for congenital heart disease were entered into a prospective study with both intraoperative transesophageal and epicardial ultrasound to determine the relative values of these techniques before and after bypass surgery. Introduction of the transesophageal probe was successful in 26 patients (93%); children were studied with use of dedicated pediatric transducers. Epicardial studies were performed in all 28 patients. Epicardial studies allowed for higher resolution imaging and a more complete assessment before bypass surgery of the intracardiac morphological condition (ventricular septum and right ventricular outflow tract) than the assessment that was obtained by the transesophageal approach. In the period immediately after bypass surgery, the transesophageal technique allowed a more detailed insight into atrioventricular valve function (valvar regurgitation [five patients] and ventricular inflow patterns) and the continuous monitoring of left ventricular function and volume. Residual interventricular shunting (three patients) or residual outflow tract obstruction (four patients) could not be reliably documented by transesophageal studies. It is concluded that intraoperative transesophageal and epicardial ultrasound in surgery for congenital heart disease are complementary rather than alternative techniques. PMID- 2245033 TI - Surgical resection of cor triatriatum in a 74-year-old man. Review of echocardiographic findings with emphasis on Doppler and transesophageal echocardiography. AB - A 74-year-old man was admitted to the hospital with congestive heart failure secondary to cor triatriatum. He also had sick sinus syndrome with complete heart block and syncope that had been treated with a permanent pacemaker 20 years earlier. The patient underwent successful surgical resection of the atrial membrane with closure of an atrial septal defect. M-mode, two-dimensional, Doppler, and transesophageal echocardiographic findings are reviewed. A unique "spike and dome" pattern on continuous-wave Doppler echocardiography is described that may suggest diagnosis of cor triatriatum. PMID- 2245034 TI - Transesophageal echocardiography in the diagnosis of left atrial appendage aneurysm. AB - Intrapericardial left atrial appendage aneurysm is rare. We describe the transthoracic and transesophageal echocardiographic findings in a 42-year-old man with atrial arrhythmia and an abnormal left atrial appendage on chest roentgenogram. Presence of an intrapericardial left atrial appendage aneurysm was confirmed at surgery. PMID- 2245035 TI - Visualization of acute pulmonary emboli by transesophageal echocardiography. AB - This report describes a patient who became hypoxic and hypotensive while awaiting cardiac surgery. An urgent transesophageal echocardiogram in the operating room showed a mass at the junction of the main and right pulmonary arteries consistent with thrombus. The thrombus was removed surgically, and the patient then had a successful aortic valve replacement. Transesophageal echocardiography is therefore useful in the evaluation of the critically ill patient. PMID- 2245036 TI - Severe tricuspid regurgitation after mitral valve repair: diagnosis by intraoperative transesophageal echocardiography. AB - Transesophageal echocardiography facilitates the evaluation of valvular repair in the operating room. The functional valvular morphology and degree of valvular regurgitation can be assessed before and after repair. This technique can also identify unsuspected findings--in this case, severe tricuspid regurgitation complicating cardiopulmonary bypass. We report a previously undescribed cause of traumatic tricuspid regurgitation. PMID- 2245037 TI - Evidence of hibernating myocardium by a new transesophageal echocardiographic technique. AB - Reversal of resting wall motion abnormalities after successful coronary angioplasty were documented in a patient with the use of a novel approach to stress testing. Transesophageal stress echocardiography utilizes transesophageal atrial pacing to provoke myocardial ischemia while the left ventricular contractility is being monitored by means of transesophageal echocardiography. The potential use of this technique is illustrated in this report. PMID- 2245038 TI - Streptococcal endocarditis temporally related to transesophageal echocardiography. AB - A case of streptococcal sanguis endocarditis temporally related to a transesophageal echocardiogram is reported; and the literature on the incidence of bacteremia occurring during transesophageal echocardiography is reviewed. On the basis of this case and review of the literature, a reevaluation of the current guidelines for endocarditis prophylaxis during this procedure is recommended. PMID- 2245039 TI - Transesophageal echocardiography: what the gastroenterologist thinks the cardiologist should know about endoscopy. AB - Transesophageal echocardiography is becoming established as a very useful addition to cardiac ultrasound. Both the applications and the number of cardiologists using this technique are growing. This article is intended to assist the cardiologist by providing information about endoscopy, including the technique of intubation, medications for sedation, medicolegal aspects, concerns of health personnel, and other related aspects. PMID- 2245040 TI - Insulin-like growth factors promote DNA synthesis and support cell viability in fetal hemopoietic tissue by paracrine mechanisms. AB - There is significant evidence that the insulin-like growth factors (IGF) play a role in both murine and human hemopoiesis. In order to better define the nature and mechanisms of these effects, we have used a serum-free system to examine DNA synthesis and cell replication in murine hemopoietic cells. Cell preparations from 13-day fetal mice livers were incubated in serum-free DMEM alone or with erythropoietin (Epo) 0.5 U/ml, recombinant human IGF-I, purified IGF-II, or recombinant human growth hormone (GH) in various doses, and [3H]thymidine added for the last 3 hr of 21-hr incubation. Cell distribution was over 80% erythroid or erythroblasts. IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive. GH was stimulatory at 1 microM. Epo was 2-9 times as effective as IGF-I and their effects were not additive. A monoclonal antibody to IGF-I reduced the effect of IGF-I by 50-80%, had no effect on Epo, and abolished the GH effect. Separation of erythroid cells and precursors from accessory and other liver cells did not alter the response to IGF-I. Cell counts increased in response to IGF-I or Epo, and cell viability was maintained by IGF-I compared to control medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245041 TI - Characterization of 5B12.1, a monoclonal antibody specific for IL-6. AB - A monoclonal antibody (MAb) specific for interleukin-6 (IL-6) was generated by fusing SP2/0 cells with spleen cells from a mouse immunized with rat spleen cell derived plasmacytoma growth factor (rat PCT-GF). This MAb inhibited the growth of an IL-6-sensitive murine plasmacytoma clone, MD90, in the presence of the immunogen, rat PCT-GF. More interesting, however, this MAb demonstrated species cross-reactivity by neutralizing murine (recombinant and P388D1 cell line derived) and human (recombinant) IL-6. IL-6 neutralization activity was also established in other IL-6 bioassays, such as the proliferation of spleen cells, plasmacytoma T1165, and a B-cell hybridoma 7TD1. IL-6 neutralization was overcome partially by increasing the concentration of PCT-GF. The MAb had no effect on PCT GF-independent plasmacytoma KI81 proliferation. Plastic petri dish-bound MAb removed rmIL-6 activity. These results suggest that this MAb specifically binds IL-6 and neutralizes bioactivity of various PCT-GF, rmIL-6, and rhIL-6. PMID- 2245042 TI - An interaction between thyroid hormone and nerve growth factor promotes the development of hippocampus, olfactory bulbs and cerebellum: a comparative biochemical study of normal and hypothyroid rats. AB - The effects of treatment with L-thyroxine (T4;20 ng/g body weight, given subcutaneously on days 1, 3, 5, 7 and 9), 2.5 S nerve growth factor (NGF; 2 ng/mg brain weight, given intracerebroventricularly on days 1, 3, 5, 7 and 9), monoclonal anti-NGF (2 ng/mg wet weight, given intracerebroventricularly on days 1, 3, 5, 7 and 9), and monoclonal anti-NGF receptor (192 IgG; 2 ng/mg wet weight, injected daily from day 1 to day 9) antibodies, separately or together, were studied on the biochemical development of hippocampal formation, olfactory bulbs and cerebellum in 10-day-old and 15-day-old normal and hypothyroid rats. The results provide the following information: (1) CNS structures other than the basal forebrain are sensitive to NGF during early development. (2) Both normal and hypothyroid rats are more sensitive to NGF deprivation than NGF supplementation. (3) The effects of anti-NGF antibodies in normal rats are similar to those induced by anti-NGFr antibodies. (4) NGF alone had little or no effect, but interacts with T4 in promoting cell maturation, especially in hypothyroid rats. (5) Hypothyroid rats are more sensitive to T4 and to T4 plus NGF than are normal ones. (6) The synergistic action of both trophic factors, but not that of T4, tend to disappear at long term in hypothyroid rats. (7) The differential sensitivity of the brain areas to T4, NGF, or both trophic factors correlates with their cell acquisition rate, especially in hypothyroid rats. (8) T4 and NGF together act more markedly (but not exclusively) on the cholinergic structures in both normal and hypothyroid rats. (9) RNA appears to be very sensitive to NGF, especially in hypothyroid rats. In close correlation with preliminary morphological observations, the results clearly demonstrate that an interaction between T4 and NGF regulates the ontogeny of a number of neuronal structures in CNS independently of their neurotransmitter phenotype, but with a regional specificity. The possibilities of accounting for this interaction, in particular the major role of thyroxine, are discussed. PMID- 2245043 TI - Heparin-mediated release of fibroblast growth factor-like activity into the circulation of rabbits. AB - Fibroblast growth factors (FGFs) are a family of structurally related proteins that influence the growth and differentiation of a variety of cell types, including the cells of the vascular system. Due to the lack of signal sequence, basic FGF is not actively secreted. However, it has been detected in the extracellular matrix bound, at least in some cases, via heparin-like molecules. Heparin has been shown to displace FGF from cells and matrices in vitro, and we have investigated the possibility that a similar phenomenon might occur in vivo. Heparin was infused intravenously into anesthesized rabbits; plasma samples taken 30 min later and monitored using [3H]thymidine incorporation into BALB/c 3T3 cells were found to contain 3-fold more stimulatory activity than control plasma samples. Addition of heparin directly to the 3T3 cells or to the plasma samples following their collection did not affect the level of stimulatory activity. A time course of stimulatory activity in rabbit plasma following heparin administration revealed that 3T3 cell stimulatory activity rapidly increased following heparin infusion, peaked at 30 min, and declined to control levels by 90-120 min. The anticoagulant action of heparin followed a different time course, providing evidence that these two effects of heparin are functionally distinct. The binding affinity of the plasma-derived stimulatory activity for heparin was used to demonstrate that the activity is FGF-like in nature. Additionally, administration of [125I]bFGF to rabbits that had been "precleared" by heparin infusion resulted in an immediate peak of circulating labeled bFGF that decreased to plateau level by 20-45 min following injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245044 TI - Long-term culture of human bone marrow stromal cells in the presence of basic fibroblast growth factor. AB - Basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow stromal cells. Normally, large numbers of human bone marrow stromal cells are difficult to obtain. However, nanogram/ml concentrations of bFGF stimulate the growth of passaged bone marrow stromal cells both in media formulated for optimal growth of stromal cells and in a simple mixture of RPMI-1640 and 10% fetal calf serum facilitating the successive expansion of stromal cells through multiple passages. bFGF also greatly accelerates the formation of a primary stromal cell layer following inoculation of newly harvested bone marrow cells into dishes. In the presence of bFGF, the stromal cells attain high densities, lose their contact inhibition and grow in multilayered sheets. Heparin greatly potentiates the stimulatory effect of low concentrations of bFGF. The effects of bFGF are fully reversible: cells cultured in the presence of this factor for multiple passages revert to normal growth rates following trypsinization and subculture. A short (4 h) exposure of the cells to bFGF elicits profound growth stimulation. This supports the hypothesis that this factor binds to glycosaminoglycans in the cell matrix which act as a storage reservoir for this cytokine. PMID- 2245045 TI - The growth of circumferential scars of the major airways from infancy to adulthood. AB - The factors affecting the development and prognosis of scarred airways in children are presented from a long-term follow-up study of 14 cases of tracheobronchial lesions following either injury or operation. Four children managed by endoluminal treatment developed severe stenosis and required treatment, later as adults, by laser resection in 2 cases and by laryngotracheal plastic enlargement and resection with anastomosis in 1 case each. The follow-up of 7 children managed by plastic procedures showed inconsistent results: they were good or excellent in 3 cases but with a decrease in the laryngotracheal diameter of 36%, 28% and 7% respectively. The laryngotracheal calibre decreased in 2 patients to 45% due to partial fibrous stenosis. Resection and anastomosis was required in the remaining 2 patients after 11 and 12 years for severe re stenosis. The 3 patients who underwent immediate surgical resection all had an excellent clinical and morphological result, with a decrease in the laryngotracheal diameter of only 7%, 13% and 19% after a follow-up of 18, 20 and 15 years, respectively. These results show that the growth capacity of scars in children's airways is closely related to residual sclerosis following the initial treatment. It is thus suggested that primary resection and anastomosis should be performed in as many cases as possible. In the performance of plastic procedures, special attention should be paid to complete resection of the fibrotic tissues. Finally, a very long postoperative follow-up is always required in children in order to assess the development of the airway. PMID- 2245046 TI - Limited and radical resection for tracheal and bronchopulmonary carcinoid tumour. Report on 227 cases. AB - Bronchopulmonary carcinoid tumours occur at all levels from the trachea to the lung periphery. Over a 20-year period. 227 patients with carcinoid tumour underwent thoracotomy. The age at operation ranged from 14 to 79 years. Haemoptysis, chronic cough, recurrent infection and wheeze were the most common symptoms; 24% of patients were asymptomatic. The primary tumour was within the trachea or the main, lobar or segmental bronchi in 190 patients (83.7%). A variety of surgical procedures were employed: pneumonectomy in 32 patients; lobectomy and bilobectomy including bronchial sleeve resection in 144; segmentectomy in 18; wedge excision in 19; bronchial sleeve only in 5; carinal resection in 2; tracheal resection in 4 and bronchotomy in 3 cases. There was only 1 hospital death in the 227 patients (mortality: 0.44%). Survival at 5 and 10 years in patients with benign carcinoid was 97.5% and 95%, respectively. In patients with the atypical form it was 41.2%. The peripheral carcinoid was usually totally removed by an ample wedge excision or segmental resection and the central bronchial carcinoid by sleeve resection with lobectomy rather than pneumonectomy. The atypical variant, because of the frequency of lymphatic involvement, should be treated as a bronchial carcinoma by radical resection. PMID- 2245047 TI - En bloc resection for bronchogenic carcinoma with chest wall invasion. Value of pre-operative radiotherapy. AB - A small number of patients with lung cancer will have a tumour invading the chest wall. Pre-operative radiotherapy and surgical resection provide the best results in patients with Pancoast's tumours, although chest wall invasion is often considered to indicate incurability. We reviewed the outcome in 46 patients with bronchogenic carcinoma and non-apical chest wall invasion and have tried to clarify the role of adjuvant pre-operative radiotherapy. All patients underwent combined chest wall and lung resection for treatment of lung cancer which had extended grossly and microscopically into the chest wall. In this retrospective study, we identified two groups of patients, those (n = 21) who received and those (n = 25) who did not receive pre-operative radiotherapy. Curative resection had been possible in 80% of the patients. There was one early post-operative death, due to pneumonia. The survival in all 46 patients is 32% at 5 years. In the most favourable cases, those without nodal involvement and who received pre operative radiotherapy, the 5-year survival is 56%. In our series, there was a notable difference in 5-year survival between irradiated and non-irradiated patients at every stage of disease. PMID- 2245048 TI - Protective influence of pretreatment with allopurinol on myocardial function in patients undergoing coronary artery surgery. AB - Xanthine oxidase is responsible for the release of free oxygen radicals during myocardial reperfusion. Allopurinol was shown to be an effective inhibitor of this reaction in the laboratory experiments, but not in patients. Thirteen male patients undergoing routine coronary artery bypass graft surgery were treated with allopurinol in doses of 15 mg/kg per day for 4 days before the operation. Haemodynamic function in the early period after cardiopulmonary bypass, ECG, enzyme release and ultrastructural findings in this group were compared with those in a control group of 13 male patients matched for age distribution and stage of coronary disease. Left ventricular stroke work index was higher in the treatment group 10 min (P less than 0.001) and 15 min after termination of cardiopulmonary bypass (P less than 0.01) and also 2 h later (P less than 0.02). In the early post-operative recovery phase fewer episodes of arrhythmia were observed in this group of patients (P less than 0.001). Electron microscopy studies of the myocardium and CK and CK-MB release showed no significant differences between groups. Thus, allopurinol may have a protective effect on the human ischaemic myocardium in the early period of reperfusion. PMID- 2245049 TI - Comparison of standard (non-oxygenated) vs. oxygenated St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol). AB - Recent studies have suggested that oxygenation of crystalloid cardioplegic solutions improves myocardial preservation. To assess whether oxygenation of St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol) improves its clinical efficacy, 50 patients were randomly assigned into 2 groups: (1) those receiving Plegisol and (2) those receiving O2-Plegisol (PO2 greater than 500 mmHg at 4 degrees C). Efficacy was assessed by (a) clinical and haemodynamic parameters, (b) quantitative birefringence changes in response to ATP and calcium as a measurement of myocardial preservation in left and right ventricular biopsies, (c) creatine kinase (MB isoenzyme) release for up to 4 days postoperatively, (d) electrocardiographic (ECG) monitoring for up to 7 days postoperatively. There were no differences in mean age, ejection fraction, aortic cross-clamp duration, or bypass duration between the 2 groups of patients. In the Plegisol group, 2 patients (8%) died and 4 patients (16%) required inotropic support, whereas in the O2-Plegisol group there were no deaths and only 2 patients (8%) required inotropic support. These differences, however, were not statistically significant. Birefringence assessment demonstrated an improved myocardial response to ATP and calcium (predominantly in the left ventricular epimyocardium and in the right ventricular biopsies) at the end of ischaemia and after reperfusion in patients given O2-Plegisol. Deterioration in cellular assessment of myocardial contractility (measured by a reduction in birefringence of greater than 0.4 nm) was reduced from 20% in Plegisol patients to 12.5% in O2-Plegisol patients. CK-MB values showed no difference at any sampling time between the 2 groups of patients; a mean peak CK-MB of 35 IU/l occurred 2 h postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245050 TI - Surgical pathology of aortic valve disease. A study based on 602 specimens. AB - A consecutive series of 602 surgically excised aortic valves was evaluated by means of macroscopic and histological study. Pure aortic stenosis was diagnosed in 140 patients, pure incompetence in 254 and combined dysfunction in 208. Of the cases with pure aortic stenosis, 38% were rheumatic, 34% were calcified bicuspid valves and 23% showed dystrophic calcification. Half the patients with pure aortic regurgitation showed aortic root dilatation. Most cases of combined aortic stenosis and regurgitation were the sequelae of rheumatic fever. A male prevalence was detectable in each group (mean male: female ratio = 2.6), and was highest in infective endocarditis and aortic root dilatation. Infective endocarditis was a frequent complication of congenitally bicuspid valves. In conclusion, rheumatic disease is still a frequent cause for surgical replacement of the aortic valve. At least half the explanted aortic valves have degenerative or congenital diseases which are often the site of a superimposed infective endocarditis. PMID- 2245051 TI - Successful bronchial revascularization in experimental single lung transplantation. AB - It is the purpose of this paper to report our experience with bronchial artery revascularization in an experimental model of single lung transplantation in swine. Thirty-three large white pigs weighing 20-40 kg underwent left lung allotransplantation. In 24 animals, bronchial artery revascularization was attempted by anastomizing the aortic patch containing the bronchial artery orifice with the recipient descending aorta. Eight survivors were put to death on postoperative days 11-15; five animals were put to death or died on postoperative days 2-9; the other animals died intra-operatively or within a few hours. Preservation of left bronchial vascularization was achieved in all cases attempted, as documented by post-mortem injection of dye (methylene blue) or contrast medium. Five of the 8 animals surviving for 11-15 days showed diffuse graft hepatization, associated with diffuse vascular thrombosis. Whether this was caused by damage to the endothelium due to poor graft preservation or by rejection was unclear. In animals surviving for 11-15 days without gross lung pathology, the anastomosis and bronchial mucosa were completely normal; in contrast, bronchial ischaemic changes were found in nonrevascularized animals and in survivors with graft hepatization. Our experience confirms that re-anastomosis of the bronchial arteries can prevent bronchial healing problems in single lung transplantation. The pig is an ideal model for these experiments since the bronchial arteries have a constant common aortic origin, allowing easy identification and preservation of left bronchial vascularization. PMID- 2245052 TI - Aberrant right subclavian artery associated with common carotid trunk. A rare cause of vascular ring. AB - We have reviewed four cases of incomplete vascular rings caused by the presence of a common carotid trunk from which arose both carotid arteries associated with an aberrant right subclavian artery. The patients were aged between 3 and 9 months. All patients presented with recurrent respiratory tract infections. Three patients showed signs of malnutrition and failure to thrive caused by episodes of bronchial aspiration from extrinsic compression of the oesophagus. One patient presented with dyspnoea induced by feeding and another had stridor. A common carotid trunk associated with an aberrant subclavian artery was confirmed in all cases. No other associated anomaly was observed in any patient. Ligature and section of the anomalous right subclavian artery was performed in all patients. The low incidence of this type of vascular ring, its physiopathological mechanism and surgical management are discussed. PMID- 2245053 TI - Technique of dissecting the internal mammary after using the Moussalli bar. AB - Since 1985 we have utilised a simple technique for dissecting the internal mammary artery (IMA) prior to coronary artery bypass surgery. The technique involves the use of a stainless steel bar (Moussalli bar) in conjunction with a Holmes Sellors sternal spreader. We have used this technique to dissect more than 2000 IMAs in patients of varying body weight and muscle build without significant complications. PMID- 2245054 TI - Patch-closure of tracheal defects with pericardium/PTFE. PMID- 2245055 TI - [Use of artificial heart ventricles in cardiovascular insufficiency of extreme degree and in heart arrest]. AB - Experiments were conducted on 26 mongrel dogs and 10 calves to evaluate the effect of uni- and biventricular bypass created by means of artificial heart ventricle on hemodynamics in acute cardiovascular insufficiency (ACVI) and heart arrest (HA). The use of unilateral right-ventricular (RVB) and left-ventricular bypass (LVB) was shown to be equivocal: in sufficient functional reserve of the left-ventricular myocardium the volume blood flow in the aorta was increased to a greater degree by RVB (to 2.1 +/- 0.3 l/min) than by LVB (to 2.0 +/- 0.5 l/min). Experiments during HA allowed the authors to evaluate selectively the bypasses in maintenance of the systemic blood flow. It was found that in univentricular bypass the other half of the heart had an effect on hemodynamics, which depended on the initial hemodynamic parameters of the divisions of circulation with high and low pressure, the filling of the heart cavities with blood, and the effect produced through the interventricular septum. The increase of the volume blood flow in the aorta in RVB to 0.6 +/- 0.1 l/min is linked to a great measure by the authors with the conducted artificial ventilation of the lungs. It was noted that the greatest difficulties in maintaining the systemic blood flow in ACVI were associated with the development of disproportion of the contractile function of the right and left parts of the heart. With consideration for this circumstance, the indications for univentricular bypass are determined. A clinical case with prolonged use of LVB (8 days) is discussed. PMID- 2245056 TI - [Nonspecific aortoarteritis and vasorenal hypertension]. AB - The article deals with the experience in surgical treatment of 157 patients with vasorenal hypertension consequent upon unspecific aortoarteritis. On the grounds of communications in the literature and their own clinical findings, the authors analyse the character of the affection in unspecific aortoarteritis and the peculiarities of the course of vasorenal hypertension and emphasize the malignancy of its course and inefficacy of nonoperative treatment. The indications and contraindications for various reconstructive operations on the renal arteries and the dependence of the results of surgery on the duration of the disease and the term of the operative intervention are discussed in detail. The authors also describe their experience in the modern methods of kidney revascularization. With the use of radiologically guided endovascular dilatation and an nitinol endoprosthesis they not only expanded considerably the possibilities of intervention on the renal vessels but improved the results of the management of vasorenal hypertension. PMID- 2245057 TI - [Combined roentgenoendovascular and direct surgical procedures in the treatment of chronic ischemia of the lower extremities]. AB - The article analyses the results of combined radiologically-guided and direct surgical operations in 27 patients suffering from chronic ischemia of the lower with multiple affections of the limb arteries. All had concomitant diseases. The radiologically guided intervention was carried out before or after a reconstructive operation. Owing to such a combination the volume of the reconstruction was reduced and its level lowered, better conditions were created for its performance, and, in some cases, correction of complications of surgical operations by the methods of radiologically-guided endovascular dilatation made it possible to avoid a repeated full-volume intervention. PMID- 2245058 TI - [Present-day vascular surgery--unsolved problems]. AB - With the establishment in the USSR of the ALL-Union Society of Cardiovascular Surgeons, a section of angiology at the All-Union Society of Cardiologists, and sections of heart and vascular surgery at the All-Union Society of Surgeons, the necessity of consolidating the efforts of all these organizations to advance and intensify the scientific and practical work in rendering adequate and effective aid to patients with vascular diseases must be recognized. Twenty-two thousand reconstructive operations were performed on the aorta and great arteries in the USSR in 1987. The main trends in vascular surgery in the USA and USSR were analysed; insufficient attention to such problems as surgery of the branches of the arch of the aorta and aneurysms of the abdominal aorta was pointed out, the need to intensify training of new angiosurgeons in the country and increase two- to threefold the number of operations performed by each one of them (to 100 reconstructive operations carried out by each surgeon annually) was substantiated. The experience of the Bakulev Institute of Cardiovascular Surgery is shown in illustration of the main organizational measures which allow the number of reconstructive operations in the cardinal branches of angiosurgery to be increased twofold. The following should be considered the main branches of angiosurgery: surgery of multifocal atherosclerosis, branches of the arch of the aorta, aneurysms of the aorta, and surgery in thromboembolism of the pulmonary arteries, reconstructive operations in injury and acute thrombosis of the great arteries, radiologically-guided surgery for recanalization of arteries and creation of new thromboresistant vascular prostheses. PMID- 2245059 TI - [Hemodynamic changes in pulmonary thromboembolism]. AB - Three variants of hemodynamic reaction to massive thromboembolism of the pulmonary artery are encountered--hyperkinetic, eukinetic, and hypokinetic. Their manifestations are determined by the patient's cardiovascular status at the onset of thromboembolism, the volume of the embolic obstruction, the degree of pulmonary hypertension, and the concomitant cardiopulmonary pathology. Effective treatment leading to marked reduction of pulmonary hypertension is conducive to increase in the proportion of the hyperkinetic type; ineffective thrombolysis, thrombosis of the inferior vena cava antiembolic filter, recurrent thromboembolism, and infarction pneumonia are the causes of diminished right ventricular systolic function and reduced cardiac index, i. e. the formation of a hypokinetic type. PMID- 2245060 TI - [Surgical treatment and prevention of angiogenic impotence in combination with revascularization of the lower extremities in Leriche's syndrome]. AB - The article deals with the results of combined revascularization of the lower limbs and penis in 29 patients with Leriche's syndrome. It was accomplished by creating an autovenous shunt between the blades of the prosthesis or common femoral artery with the dorsal artery of the penis. In the late-term postoperative period the initially lost sexual function was restored in 6 patients and improved or maintained on the preoperative level in 16 patients. On the basis of comparison of the results with the sexual function in patients who were treated by bifurcation aortofemoral shunting it is concluded that the suggested surgical tactics in the prevention and treatment of vasculogenic impotence in Leriche's syndrome produces a significant clinical effect. PMID- 2245061 TI - [Epicardial destruction of the bundle of Kent by pulsating electric current and the criteria of its effectiveness in Wolff-Parkinson- White syndrome]. AB - The article deals with a new method of treatment of the Wolff-Parkinson-White syndrome. The operation for epicardial destruction of Kent's bundle by pulsating current was developed by the authors. It is distinguished by its simplicity and the possibility to determine the efficacy of the procedures during the operation itself. The results of examination of 44 patients in the early postoperative period and in late-term periods after this operation are discussed. It was found that the electric factor does not cause structural changes of the underlying structures and does not affect the pumping function of the myocardium. The revealed changes were recorded by means of angiocardiography, coronarography, radionuclide ventriculography, and the enzyme spectrum. PMID- 2245062 TI - [Familial bullous disease of the lungs as a cause of spontaneous pneumothorax]. AB - Problems of surgical treatment of familial spontaneous pneumothorax, which is a manifestation of a hereditary form of bullous disease of the lungs, are discussed. Study of 2 families showed that the disease is inherited according to the autosome-dominant type with incomplete penetrance and/or variation expressivity. Operation was performed on 5 of 9 patients. Bullectomy and pleurodesis by means of parietal pleurectomy were conducted. Follow-up for periods of 1 to 27 years showed surgical treatment to be effective. PMID- 2245063 TI - [Use of fibrin glue in pulmonary surgery]. AB - The article deals with the experimental data on the use of the "Beriplast" (GFR) and phi K-1 (USSR) fibrin glue (FG) for providing hemostasis and hermetization of the resected surface of the lung. The results were evaluated during the operation by the method of pneumopressure and by means of morphological studies. The "Beriplast" FG was applied in the clinic for aerostasis in incomplete +hermetization of the sutured pulmonary wound in 11 patients. Complete +hermetization was produced in all cases. Complications linked with the use of FG were not encountered. PMID- 2245064 TI - [Arteriovenous fistulas of the lungs in children]. PMID- 2245065 TI - [Computerized tomography in the surgery of esophageal cancer]. AB - Preoperative X-ray computerized tomography (CT) was performed in 60 patients with carcinoma of the esophagus at the All-Union Oncology Research Centre, USSR AMS in 1986-1989. The method is evaluated on the basis of comparison with the operative findings in determining the depth of invasion of the esophageal wall and adjoining structures by the tumor, metastatic involvement of the lymph nodes below the diaphragm, and metastases in the liver. Informativeness of X-ray CT proved to be highest in patients in whom the tumor had not spread beyond the esophageal wall. It was established that the method possesses high resolving possibilities in identification of enlarged lymph nodes in the abdominal cavity. Small metastases in the liver, measuring 0.5 to 2 cm in diameter, cannot be revealed by the method in some cases. The data gained by means of X-ray CT allows tactics of the surgical intervention to be determined and the late-term results to be predicted. PMID- 2245066 TI - [The system of administration of cardioplegic solutions]. PMID- 2245067 TI - [Time factor in surgical treatment of acute myocardial infarction]. PMID- 2245068 TI - [Radical correction of tetralogy of Fallot in kinking of the right pulmonary artery after earlier performed Cooley-Edwards anastomosis]. PMID- 2245069 TI - [Thrombosis of mitral valve prosthesis during pregnancy]. PMID- 2245070 TI - [Rare complications of electric cardiac stimulation]. PMID- 2245071 TI - [Aortic and right-atrial fistula after knife injury]. PMID- 2245072 TI - [Successful surgical treatment of total rupture of the main bronchus in closed chest trauma]. PMID- 2245073 TI - [Gunshot multiple trauma in a child]. PMID- 2245074 TI - [Pleuro-biliary fistula after gunshot thoraco-abdominal injuries at peace time]. PMID- 2245075 TI - [Foreign body (scalpel) in the pleural cavity]. PMID- 2245076 TI - [Postoperative multiple chondritis of the ribs in oncological patients]. PMID- 2245077 TI - [Anterior cerebral artery occlusion clinical analysis of 27 self-experienced cases]. AB - From the years 1977 through 1989, the author experienced 27 cases with only anterior cerebral artery (ACA) occlusion but without any other main cerebral arterial occlusions. These were proven by cerebral angiographies and verified by CT. Two patients showing large infarction in the left frontal lobe on CT but showing no evidence of arterial occlusion by cerebral angiography were also registered in this study because these patients were thought to have recanalized ACA. There were 15 males and 12 females with an age of 61.5 +/- 7.98 (mean +/- SD) and 66.1 +/- 6.45, respectively. Twenty two cases had cerebral thrombosis and 5 had cerebral embolism. There were 4 cases with bilateral ACA occlusions, 8 with right ACA occlusion and 15 with left ACA occlusion. Twenty two patients (81%) were alert on admission and this fact might explain their excellent ADL on discharge: full recovery in 9 patients (33%) and self-management in 12 patients (44%). Seventeen patients (63%) had a CT-proven infarcted area with a correlation to ACA occlusion (s), while 9 patients (33%) showed no correlation between an infarction on CT and an ACA occlusion. One patient showed no abnormal findings on CT. Four patients with right ACA occlusion were incidentally observed, even though their mode of onset was strokes. The symptoms of the other 23 patients were those of anterior cerebral artery syndromes: hemiparesis (74%), urinary incontinence (39%), forced grasping (39%), mutism (30%), indifference (26%) and apraxia (22%) etc. PMID- 2245078 TI - [Computerized analysis of EEG background activity in mono-therapeutic patients with epilepsy--relationships between antiepileptic drugs and types of seizures]. AB - EEG background activity influenced by antiepileptic drugs (AED) was studied in 109 monotherapy and drug-free epileptic patients using t-Statistical Significance Probability Mappings (t-SPMs). Patients taking phenobarbital (PB) had an increase in alpha 1 and a decrease in alpha 2 activity in comparison with drug-free epileptics. Patients taking PB for generalized seizures with tonic-clonic convulsion only (GTC) also had a significant increase in alpha 1 and a decrease in alpha 2, whereas those with partial seizures (PS) had an increase in theta and beta 1 and a decrease in alpha 2 activity. Patients taking valproic acid (VPA) had a decrease in only beta 1 activity. Patients taking VPA for GTC showed an increase in delta activity, but those with PS did not show any changes. Patients taking carbamazepine (CBZ) for PS exhibited marked slowing with an increase in theta and alpha 1 and a decrease in alpha 2 activity. These results mean that changes in EEG due to AEDs differ depending on the type of seizures. More interestingly, discrepancy between EEG background activity and effects of AEDs was found: In PS type of seizures, the most effective CBZ exhibited striking slowing, PB was next, and VPA was last. In GTC, VPA resulted in greater slowing than PB. PMID- 2245079 TI - [Behavioral and histochemical observation in rotational rat with adrenal medulla transplantation]. AB - It is widely known that rotation rat is prepared by destroying substantia nigra pars compacta in the rat. Adrenal medulla was transplanted to the rat. The transplantation was judged to be effective in the rat to which adrenal medullary cell was transplanted as the number of rotation decreased evidently in the rat with transplanted adrenal medulla even in the change in the rotating motion after actual transplantation. On the other hand, many transplanted cells transformed into nerve cell which was considered to have produced dopamine were observed in the rat in which transplantation was judged as effective in the histochemical assessment made of the group undergone transplantation of the adrenal medulla. However, in the rat in which no decrease in the number of rotation was observed, only the transplanted cells which were presumed to be the primary adrenal medullary cells were existent. The fact suggests that take of dopamine-producing cells is necessary to see decrease in rotating motion which is found to be the judging criterion for clinical effect. PMID- 2245080 TI - [Chronic cervical epidural hematoma diagnosed by magnetic resonance imaging]. AB - The clinical picture of spinal epidural hematoma is usually characterized by the sudden onset of pain and acute paraplegia within a few hours. The reports of chronic spinal epidural hematoma above the lumbar level is extremely rare. Here we added one case whose hematoma was at cervical level. A 31-year-old previously healthy male suffered from continuous sharp pain in the back of his neck about 10 weeks before admission. He took analgesic drugs and treated with head traction by his home doctor with minimal relief. 4 weeks later from onset progressive weakness and numbness appeared at his right hand and arm. Physical examination on admission revealed mild monoparesis and sensory disturbance in his right upper limb. There was hyporeflexia of both upper extremities. Magnetic resonance imaging (MRI; Hitachi 0.2 T) visualized a dorsal epidural space occupying lesion extending from C3 to Th1 vertebral body level. This revealed high signal intensity in T2 weighted image and mixed (low and iso) signal intensity in T1 weighted image corresponding to old hematoma. All his medication was stopped and he treated with collar brace, which improved his neurological status. 3 weeks later, he recovered fully and follow-up MRI revealed the total absorption of the hematoma. Left vertebral angiogram showed that a part of posterior cerebral venous blood drained to cervical vertebral plexus. This finding suggested his epidural bleeding was venous in origin. Rupture of internal vertebral venous plexus that has no valves was considered as the source of spinal epidural hematoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245081 TI - [Successful treatment of Candida meningitis with miconazole]. AB - This paper presents a case of successful treatment of candida meningitis with miconazole. A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986. Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH. Candida albicans was cultured from her CSF. The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations. Combination therapy (amphotericin B and flucytosine) was initiated. However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B. Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200 1200 mg/day, total 70.4 g) was begun on November 23. Clinical and CSF findings were improved soon. No side effect of miconazole was observed. After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987. Reports of mycosis in central nervous system are recently increasing, especially for candidosis. Cryptococcosis is noted frequently as an opportunistic infection of AIDS. The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis. Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance. Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis. Few side effects have been reported with its use. The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245082 TI - [Torticollis as an initial symptom of adult-onset dystonia musculorum deformans]. AB - Dystonia musculorum deformans (DMD) is an idiopathic movement disorder which usually involves pediatric age group and progresses to the generalized type. On the contrary in adult-onset DMD, dystonia is usually confined to an upper extremity and its clinical course is benign. The authors report seven patients with adult-onset DMD whose initial symptom was confined to the neck. Diagnosis of idiopathic spasmodic torticollis had been made in all of them. Average ages at the onsets of torticollis and extranuchal dystonia were 49 +/- 13 and 54 +/- 9 years (mean +/- SD) respectively. The duration between these onsets was 2-3 years in five patients and 10-17 years in two younger patients. Two patients finally developed generalized dystonia and one patient became hemidystonic type. These findings suggest that some patients diagnosed as idiopathic spasmodic torticollis are in an early stage of DMD and that this particular type progresses more likely to the generalized form than other types of adult-onset DMD. PMID- 2245083 TI - [A case of left internal capsular infarction with auditory hallucination and peculiar amnesia and dysgraphia]. AB - A 46-year-old businessman suddenly became to behave curiously on the morning, September 1, 1988. He forgot how to go through an automatic ticket gate, which he used every day. In his company, he also forgot how to open the cash box, and he wrote a meaningless report for his business. From the night on that day, he had experienced auditory hallucination in which whispering words of some criticism to his performance for a few days. On the next day, he was admitted to a psychiatric hospital because he was suggested to have schizophrenia. By day 6 after the onset, his curious symptoms completely disappeared. However, slight verbal memory disturbance and cognitive dysfunction still remained. Because the brain CT on day 6 showed a small localized subcortical infarction in the left hemisphere he was transferred to our clinic on day 20 to elucidate the relation between the abnormal behavior and the infarction. His blood pressure was 116/64 mmHg and pulse was regular 63/min. He was clear and did not have any neurological deficit. He kept his episodic memory regarding the events at the onset and could almost recall them precisely. Results of standard blood tests, electrocardiogram, ultrasound cardiogram, electroencephalogram as well as cerebral angiography were normal. Computed tomography and magnetic resonance imaging showed an infarcted lesion in the genu of the left caudate nucleus, adjacent to the anterior part of the thalamus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245084 TI - [Long-term results of hydrocephalus with myelomeningocele]. AB - This paper reviews long-term follow-up studies of 78 hydrocephalic patients with myelomeningocele. Seventy-eight (95%) out of 82 patients with myelomeningocele had hydrocephalus. CT, MRI, CT cisternography, and monitoring of intracranial pressure (ICP) with infusion methods were performed to evaluate the indication of shunt insertion or shunt independency. These hydrocephalic patients consisted of the following two groups: (1) Early treated group. Sixty-four cases received initial cerebrospinal fluid (CSF) diversion operation within 2 years of life. Sixty-three patients had a ventriculoperitoneal (VP) or a ventriculoatrial (VA) shunt. All the patients of this group showed progressive signs and symptoms of increased ICP due to hydrocephalus. The mean age at the initial shunt placement was 10 weeks. The mean value of Evans' index before shunting was 47%, which corresponded to moderate ventriculomegaly. 48% of this group showed slit-like ventricles on postoperative CT scans, where 52% had normal or only mildly dilated ventricles subsequent to shunting. There were two instances (3%) of the so-called "slit ventricle syndrome" and one instance of "isolated fourth ventricle", who had undergone multiple shunt revisions. Shunt revisions were performed on fifty two occasions in this group. The mean number of shunt revisions per child was 2.8. Sixty among 64 patients of this group were suitable for evaluating shunt dependency with long-term follow-up period. Forty-two out of 60 patients were considered to be shunt dependent, who underwent multiple shunt revisions after 6 months of age. These patients had signs and symptoms of increased ICP, neurological deterioration, and enlarged ventricles when their shunts were blocked. There were four cases of slowly progressive (shunt dependent) hydrocephalus, who did not show clinical signs and symptoms of shunts malfunction in spite of progressive ventriculomegaly and abnormal findings of CT cisternography and ICP monitoring. Only two patients (3%) proved to be shunt independent. Consistently their ventricles were mildly dilated. These results suggest a very low incidence of true arrest of hydrocephalus after shunt operation. (2) Late treated group. Fourteen cases were diagnosed or treated for hydrocephalus after 7 years of age. Six out of fourteen patients had remarkable hydrocephalus whose Evans' index exceeded 51%. The mean value of Evans' index was 48% in this group. Six patients had progressive signs and symptoms of hydrocephalus and were shunted. ICP monitoring and studies of CSF dynamics revealed abnormal findings in ten out of 14 cases in spite of preservation of good intelligence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245086 TI - The behavioural sciences. PMID- 2245085 TI - [Cerebral blood flow and brain size in healthy subjects--sensitivity to age and gender]. AB - Cerebral blood flow was measured in 56 healthy subjects who ranged in age from 1.3 to 80 years. The Xe-133 inhalation method with ring type single photon emission computed tomography (SPECT); HEADTOME was used. The cerebral blood flow were calculated by the method of Kanno & Lassen. Then the value were corrected for end-tidal CO2 concentration that had an excellent correlation with PaCO2 and was one of the most sensitive factors to change cerebral blood flow. The brain size index was obtained by measuring the lateral and antero-posterior diameters from the SPECT images. The mean cerebral blood flow in children less than five years of age was 90-100 ml/100 g/min that was approximately twice that found in adults. The mean cerebral blood flow decreased rapidly with age until 24.0 years of age in male and 21.7 in female. Thereafter, there was a slow decrease and a negative correlation with age was found. In adults, the mean value of the cerebral blood flow of females was slightly higher than that of males (p less than 0.01). In contrast, the brain-size index of females was significantly smaller than that in males (p less than 0.01). There was a significant negative correlation to an inverse proportionality of cerebral blood flow and brain-size index (p less than 0.002). But, there was no significant correlation between total flow index that obtained to multiplied mean flow by brain-size index and brain-size index or gender. PMID- 2245087 TI - Soft drinks, infants' fruit drinks and dental health. AB - Dr Trevor Grenby and his fellow research workers have recently completed a research project on the dental properties of adults' and infants' soft drinks. Here, he uses these findings as a basis for giving his personal opinions on the drinks and their possible influence on dental health. PMID- 2245089 TI - 'The rhetoric of specialisation'. PMID- 2245088 TI - 'Surgeons fear threat of AIDS in the air'. PMID- 2245090 TI - Contact allergy. PMID- 2245091 TI - 'DIY dentures'. PMID- 2245092 TI - A comparison of ibuprofen and ibuprofen-codeine combination in the relief of post operative oral surgery pain. AB - Non-steroidal anti-inflammatory analgesics are commonly prescribed to out patients who have undergone oral surgical procedures, since they are said to provide excellent pain relief for mild to moderate pain, allied with minimal side effects. One hundred patients were entered into a randomised clinical trial to compare the efficacy of a simple non-steroidal analgesic with that of a combination analgesic compound following the removal of lower third molars under local anaesthesia. Pain scores were measured for patients post-operatively by means of a verbal rating scale for 3 days and data were analysed using the Mann Whitney U-test. Results suggest that this combination product offers no advantages (but shows definite disadvantages) when compared to an effective non steroidal anti-inflammatory product. PMID- 2245093 TI - A severe asthmatic reaction to poly(methyl methacrylate) denture base resin. PMID- 2245094 TI - Dental caries and periodontal disease in Papua New Guinea. AB - Last year I spent my elective in Papua New Guinea. I surveyed the prevalence of dental caries and periodontal disease among the Papua New Guineans and found that rates of disease were higher than those found in earlier studies. Changing diet, poor oral hygiene and a chronic shortage of trained dental staff are the main culprits. PMID- 2245095 TI - Desmond Greer Walker Award. Enamel mottling in a non-fluoride community since the advent of fluoride toothpastes. AB - In 1987 an assessment of mottling in incisor teeth was carried out on a random sample of 12-year-old children in Liverpool, England. The number of children examined was 471. All of these children were born and had lived in Liverpool when the fluoride content of the water supply had averaged 0.1 parts/10(6). During this time the market share of fluoride toothpastes had increased from 5% in the early 1970s to 91.8% in 1987. The mouth prevalence of mottling was found to be 31.1%. The tooth prevalence of mottling was found to be 7.83%. There was no sex difference. The data obtained was compared with findings in 1974-75 in Liverpool before the advent of fluoride toothpastes. The data suggests that there has been a decrease in the prevalence of mottling in Liverpool since 1974-75. PMID- 2245096 TI - [Accident risk and development of seriousness level of winter sports accidents]. AB - Ski accidents are quite frequent but not alarming if we consider the benefit of the out door sporting. In the region of Davos-Klosters more than 5 Mio Km of vertical drop are performed in down hill skiing. They result in approximately 1300 accidents per year. Since 1972 more than 20,000 ski accidents were analysed. The injuries of the lower extremity have slightly decreased (44%), on the other hand we observe more injuries of the upper extremity (32%). There are only a few polytrauma patients registered, mainly on the basis of too high speed on the ski slopes. Fractures have become rather uncommon at least in relation to the complex knee injuries which today amount to 50% of all the injuries of the lower extremities. For the prevention of ski accidents a detailed control of the equipment, especially the safety bindings at the beginning of each winter season is of utmost importance. PMID- 2245097 TI - [Changes in skiing accidents during the last 20 years]. AB - Since 23 years the skiing-accidents are statistically surveyed in the private practice of the author. The number of injured patients is continuously decreasing. Specially the injuries in years with little snow fall are analyzed. It is evident that leg fractures are quite rare but severe injuries of the knee are increasing. 50% of ski accidents are minor injuries. PMID- 2245098 TI - [Prevention of skiing accidents in Switzerland]. AB - In Switzerland, the prevention of skiing accidents has had a long tradition. The prevention of skiing accidents concept is based on three elements: "The facilities (slopes, runs), the equipment, the human-being". Together with partner organisations (the authorities, federal offices, medical circles, trade and sport associations), the Swiss Council for Accident Prevention bfu has put together an extensive package of measures for the increase of safety in skiing. The efforts made over the years are showing results. Since the beginning of the eighties, the number of skiing accidents which take place in Switzerland every year shows a decreasing trend. PMID- 2245099 TI - [Skiing and safety from the viewpoint of a pro. Observations on adventures and experiences of a top athlete]. PMID- 2245100 TI - [Hazardous sports and insurance]. AB - In spite of increased efforts in the prevention of recreational accidents the SUVA has to state that, as before, there is a steady increase in non-occupational accidents. 33% of all non-occupational accidents are caused through sport. Preventive measures and optimum patient treatment are effective moves to limit the costs. Shortening the financial benefits in heavy-risk sports (hazardous ventures) or in grave infringement of elementary cautionary obligations (gross negligence) should aim less at a cost saving than at an overall preventive effect. PMID- 2245101 TI - [Frostbite: findings May 1990]. AB - Frostbites are a frequent pathology in mountain sports; we treat 80 cases per years in Chamonix. Usually due to a bad equipment, they are favoured by humidity, wind, the high altitude polycythemia and dehydration. Physiopathology associates a physic phenomenon (freezing) with a vasomotor response. Diagnosis is obvious; the forecast rests on the bone scintigraphy and treatment combines fast warm up, vasodilators, hemodilution and late surgery. Only 8% of our patients have amputations. The best treatment is prevention. PMID- 2245102 TI - [Hanggliding accidents: epidemiology and clinical aspects]. AB - The authors reviewed their experience with hanggliding injuries, and additional cases in the literature. As most accidents are due to how people fly (inexperience), and where people fly, the authors conclude that an adequate training is mandatory. PMID- 2245103 TI - [Accidents and injuries in hanggliding]. AB - Between January 1987 and December 1988 36 patients with injuries resulting from hanggliding were admitted to the Interlaken hospital. 6 (17%) of them were women. 14 patients were between 20-30 years old. 24 patients presented injuries of the lower limb, in 10 cases the spine was affected. From the total 39 injuries 20 had to been treated by operation. The accidents occur equally while starting or landing, during the flight incidents are very rare. The majority of the patients had only little experience in hanggliding or underwent insufficient training, indicating the most important point to be dealt with in the future. PMID- 2245104 TI - [Death in an avalanche]. AB - Report about two accidents with avalanches. In the first the author himself was a victim and already unconscious. In the second he was a witness and engaged in the rescue procedures, however both of our friends lost their lives while 2-2.5 meters under the snow. PMID- 2245105 TI - [Craniocerebral trauma and skiing: the ABC of the general surgeon]. AB - This paper describes the classical encephalic lesions due to ski accidents, after a short review of the normal cerebral physiology. It analyses the main steps of the management of the head injury patient by the general surgeon taking history, general and neurologic state, diagnosis, first aid, initial medication, transport conditions and information of the neurosurgical center. PMID- 2245106 TI - Exercise and heart disease: is there still a controversy? PMID- 2245107 TI - Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study. AB - Data from 10,359 men and women aged 40-59 years from 22 districts in the Scottish Heart Health Study were used to describe the prevalence rates of coronary heart disease in Scotland in 1984-1986 and their relation to the geographical variation in mortality in these districts. Prevalence was measured by previous history, Rose chest pain questionnaire, and the Minnesota code of a 12 lead resting electrocardiogram. The prevalence of coronary heart disease in Scotland was high compared with studies from other countries that used the same standardised methods. A history of angina was more common in men (5.5%) than in women (3.9%), though in response to the Rose questionnaire 8.5% of women and 6.3% of men reported chest pain. A history of myocardial infarction was three times more common in men than women, as was a Q/QS pattern on the electrocardiogram. There were significant correlations between the different measures of coronary prevalence. District measures of angina correlated well with mortality from coronary heart disease, and these correlations tended to be stronger in women than in men. There was no significant correlation between mortality from coronary heart disease and measures of myocardial infarction. The study provides data on the prevalence of coronary heart disease in men and women that are valuable for the planning of cardiological services. PMID- 2245108 TI - Transient myocardial ischaemia after acute myocardial infarction. AB - The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications. PMID- 2245109 TI - Relation between intraventricular pressure and volume in diastole. AB - The pressure-volume curves for 10 patients with various types of heart disease were studied throughout mid to late diastole when both pressure and volume were increasing. The results were used to test a currently held theory that the form of this relation is exponential. It was found that for the patients examined this hypothesis was not valid. PMID- 2245110 TI - Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer. AB - Many exercise protocols are in use in clinical cardiology, but no single test is applicable to the wide range of patients' exercise capacity. A new protocol was devised that starts at a low workload and increases by 15% of the previous workload every minute. This is the first protocol to be based on exponential rather than linear increments in workload. The new protocol (standardised exponential exercise protocol, STEEP) is suitable for use on either a treadmill or a bicycle ergometer. This protocol was compared with standard protocols in 30 healthy male volunteers, each of whom performed four exercise tests: the STEEP treadmill and bicycle protocols, a modified Bruce treadmill protocol, and a 20 W/min bicycle protocol. During the two STEEP tests the subjects' oxygen consumption rose gradually and exponentially and there was close agreement between the bicycle and the treadmill protocols. A higher proportion of subjects completed the treadmill than the bicycle protocol. Submaximal heart rates were slightly higher during the bicycle test. The STEEP protocol took less time than the modified Bruce treadmill protocol, which tended to produce plateaux in oxygen consumption during the early stages. The 20 W/min bicycle protocol does not take account of subjects' body weight and consequently produced large intersubject variability in oxygen consumption. The STEEP protocol can be used on either a treadmill or a bicycle ergometer and it should be suitable for a wide range of patients. PMID- 2245111 TI - Operative findings after percutaneous pulmonary balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. AB - Since 1983 percutaneous balloon dilatation of the right ventricular outflow tract has been performed as an alternative to surgical palliation in selected cases of tetralogy of Fallot at the Royal Liverpool Children's Hospital. From 31 December 1984 to 31 December 1988, 27 of these patients underwent subsequent surgical correction. Age at operation ranged from 7 to 58 months (median 2.7 years). The mean interval between balloon dilatation and correction was 15.6 months (range 3 39 months). Two patients had a systemic pulmonary shunt operation performed before dilatation and a further five required one afterwards. Overall 20 (74%) patients had some anatomical alteration as the result of balloon dilatation, while in seven (26%) there was no discernible change in the right ventricular outflow tract. There was no consistent relation between the ratio of balloon size to pulmonary annulus diameter and the morphological findings. Balloon dilatation may obviate the need for systemic-pulmonary shunt at the expense of some structural damage, particularly to the posterior cusp. The present data suggest that dilatation does not bring about growth of the annulus to such an extent that transannular patch is no longer needed at intracardiac repair. PMID- 2245112 TI - Tetralogy of Fallot with anomalous pulmonary venous connections: a rare but clinically important association. AB - Anomalous pulmonary venous connections were found in seven (0.6%) of 1183 patients with tetralogy of Fallot. Three patients had totally anomalous connections (one supracardiac, one direct to coronary sinus, and one mixed supracardiac and infracardiac) and four patients had partially anomalous pulmonary venous connections. All patients presented with the clinical features of tetralogy of Fallot. Anomalous pulmonary venous drainage was suspected clinically in only one patient in whom there was a scimitar sign on the chest radiograph. The exact diagnosis was established by cross sectional echocardiography (one), preoperative or postoperative angiography (five), or at necropsy (one). Surgery was performed in six patients. Total correction without re-routing of the anomalously draining veins was successful in all those with partially anomalous connections, with no significant long term sequelae (follow up median 17 years). Of those with totally anomalous connections, the full diagnosis was made only at necropsy in one patient, successful one-stage correction was performed in one, and the other patient, who had partially obstructed mixed drainage, died shortly after one-stage correction. Histological examination of the lung biopsy specimen in this patient showed grade 2 pulmonary vascular disease. Tetralogy of Fallot with anomalous pulmonary venous connections is a rare association. Careful preoperative assessment is required in those with totally anomalous connections. PMID- 2245113 TI - Diagnostic echocardiographic features of the sinus venosus defect. AB - To establish the diagnostic criteria for a sinus venosus atrial septal defect cross sectional echocardiograms, cineangiograms, and surgical notes of all patients with this diagnosis seen at the Children's Hospital of Pittsburgh between 1986 and 1988 were reviewed. Seven patients were identified. In each the extent of the atrial septum and the nature of the junction of the superior vena cava with the atria were evaluated echocardiographically from the subcostal position. All had overriding of the superior vena cava and abnormally connected right pulmonary veins. Six patients had undergone cardiac catheterisation and cineangiography. Five patients underwent surgical repair. The operative findings were consistent with the expected morphology in all five, and these features were additionally confirmed in a specimen from the cardiopathological museum. Therefore, the basic anatomical feature of a superior sinus venosus interatrial communication is a biatrial connection of the superior vena cava. This, together with anomalous drainage of the right sided pulmonary veins, results in an interatrial communication outside the confines of the true atrial septum. Overriding of the superior vena cava across the upper rim of the oval fossa is suggested as the pathognomonic diagnostic feature that can clearly be demonstrated echocardiographically from the subcostal position. In essence the lesion is an interatrial communication rather than an atrial septal defect. PMID- 2245114 TI - Coarctation of the aorta and post-stenotic aneurysm formation. AB - Despite earlier angiography, post-stenotic aneurysm of the aorta was an unexpected finding at operation in two patients with coarctation. One aneurysm was found in an intercostal artery in a 19 year old man and the other was a false aneurysm just distal to the coarctation site in a 7 year old boy. These aneurysms are fragile, apt to rupture, and difficult to diagnose preoperatively. Though local factors such as jet streams and bacterial endocarditis may influence their formation there must be an underlying generalised weakness in the arterial wall. A coarctation should not be regarded as an isolated arterial abnormality because it may be a feature of a more generalised disease. Because of the risk of rupture, which may not be prevented by antihypertensive treatment, operation should not be delayed in any age group. PMID- 2245115 TI - Supravalvar aortic stenosis: a complication of aortic valve surgery. AB - After a patient had aortic valvotomy and aortotomy for the relief of valvar aortic stenosis supravalvar stenosis developed over the next six years. PMID- 2245116 TI - Aortic atresia: survival to adulthood without surgery. AB - Aortic atresia is a rare congenital cardiac defect. It usually leads to death in the neonatal period. A patient with aortic atresia has survived to the age of 24 years without any surgical procedure. In view of the uncertain results of reconstructive surgery this case may have therapeutic implications. PMID- 2245117 TI - Restoration of sinus rhythm during two consecutive pregnancies in a woman with congenital complete heart block. AB - In a woman with congenital complete heart block atrioventricular conduction was normal during two successive pregnancies. Pregnancy, labour, and delivery were uncomplicated on both occasions and complete heart block returned post partum. PMID- 2245118 TI - Eustachian valve endocarditis. AB - M mode and cross sectional echocardiography showed a highly mobile globular pedunculated mass(3.0 cm long with a maximum diameter of i.5 cm) attached to the eustachian valve in a heroin addict with staphylococcal endocarditis. PMID- 2245119 TI - Balloon dilatation of the mitral valve by a single bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter. AB - The efficacy of balloon dilatation of the mitral valve by a bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter (single catheter technique) was assessed in 53 patients (mean age 28) with mitral stenosis, most of whom were women. The procedure was unsuccessful in three patients. After balloon dilatation the left atrial pressure decreased from 22 mm Hg to 13 mm Hg and the mitral valve gradient from 12 mm Hg to 4 mm Hg. The mitral valve area increased from 0.7 cm2 to 2.1 cm2. Exercise time on the standard Bruce protocol increased from 3.9 minutes to 7.2 minutes. In 22 (44%) patients mitral regurgitation developed or the grade of regurgitation increased. Left to right shunts with pulmonary to systemic flow ratios greater than 1:5 were detected in four patients. Transient cerebrovascular episodes developed in two patients. One patient died after emergency valve replacement for severe mitral regurgitation. Balloon dilatation of the mitral valve by the single catheter technique with the bifoil or trefoil catheters is an effective treatment for patients with mitral stenosis. Mild mitral regurgitation is a frequent complication of the procedure. PMID- 2245120 TI - Non-invasive determination of cardiac output by Doppler echocardiography and electrical bioimpedance. PMID- 2245121 TI - Intra-ocular lenses for cataract patients. PMID- 2245122 TI - Pulmonary uptake of MDP: demonstration of site by correlation of emission and transmission computed tomography. PMID- 2245123 TI - Intra-operative ultrasound in the surgery of insulinomas. PMID- 2245124 TI - Some Plymouth worthies (Part 2). PMID- 2245125 TI - The medicine of the people; the survival of classical medical ideas into modern popular usage. PMID- 2245126 TI - Quality through ages: welcome to the first Erasmus Winterschool in Leiden, 5-10 February 1990. PMID- 2245127 TI - Enzyme histochemical methods applied in the brain. AB - Catalytic enzyme histochemistry offers the possibility to demonstrate enzymes qualitatively and their activities quantitatively in brain sections at those sites where they are localized. To get an appropriate histochemical demonstration of enzymes, requirements are to be fulfilled with respect to the preparation of brain tissue, the detection methods, and the incubation conditions. For enzyme demonstration at the light microscopic level, brain tissue should be frozen as quickly as possible and for those at the electron microscopic level perfusion fixation using low concentrations of aldehydes seems to be best suited. The detection of enzymes in brain sections is preferentially performed by the so called precipitation reactions with metallic ions, the tetrazolium and the diaminobenzidine methods. The application of these methods was shown in the example of aspartate aminotransferase, glutamate dehydrogenase, and cytochrome c oxidase. In the detection of enzymes incubation conditions should be chosen so that soluble enzymes cannot diffuse out of the sections into the incubation media and that the activities of enzymes are completely demonstrated. On the whole, all the precipitation reactions result in a water-insoluble reaction product which is precipitated at the enzymatic sites in brain sections. Finally, it is shown that scanning microphotometry is a valuable tool for the quantification of enzyme activities in brain sections. It is concluded that catalytic enzyme histochemistry using improved detection methods could be a source of results complementary to those provided by immunocytochemistry and microchemistry. PMID- 2245128 TI - Microwave-stimulated brain enzyme incubations are possible at the unphysiological condition of 50 degrees C. AB - Microwave-stimulated enzyme incubations for acetylcholinesterase, 5' nucleotidase, alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, succinic dehydrogenase and isocitric dehydrogenase were studied, and compared with incubations in a waterbath. Temperature settings of 37 degrees C and 50 degrees C were used, and the incubation times were varied from 30 seconds to 30 minutes. The desired temperature of the incubation solution was reached in the microwave oven within 1 minute, whilst in the waterbath it took 10 to 25 minutes. The microscopic results for alkaline phosphatase and succinic dehydrogenase at a temperature setting of 50 degrees C were superior in the microwave method for incubation times less than 15 minutes. It is postulated that the increased reaction product of alkaline phosphatase and succinic dehydrogenase is due to a temperature effect, which has to be large enough to be of practical value. For the other enzymes studied, microwave-stimulated incubations were no better than the conventional incubations at corresponding temperatures. For 5'-nucleotidase there were aspecific lead deposits in the microwave method. All enzymes performed at the elevated, unphysiological temperature of 50 degrees C proved to have advantages, except for 5'-nucleotidase, whilst for malate dehydrogenase there was an aspecific reduction of the colour developer at this temperature. PMID- 2245129 TI - Principles of the 2-deoxyglucose method for the determination of the local cerebral glucose utilization. AB - Sokoloff and co-workers developed the 2-deoxy-D-[1-14C]glucose (2DG) method in order to study the local cerebral glucose utilization (LCGU) of discrete brain regions in vivo. Energy metabolism of the adult mammalian brain is almost entirely dependent on glucose. The majority of the glucose taken up by the brain is needed for the maintenance of the membrane potentials and the electrical activity. The functional activity could thus be shown to be closely linked to energy metabolism. Consequently, examination of the energy metabolism by measuring the cerebral metabolic rate for glucose can provide information concerning functional activity in all of the neuroanatomically defined regions of the brain. Studying the fate of experimentally injected 2-deoxy-D-[1-14C]glucose, a radioactive labeled analogue of glucose, and, subsequently, employing quantitative autoradiographic techniques, it is possible to estimate the levels of the local cerebral glucose utilization in specific regions of the brain. According to Sokoloff (1982) the LCGU represents a "metabolic encephalography". PMID- 2245130 TI - Neural network simulations of the nervous system. AB - Present knowledge of brain mechanisms is mainly based on anatomical and physiological studies. Such studies are however insufficient to understand the information processing of the brain. The present new focus on neural network studies is the most likely candidate to fill this gap. The present paper reviews some of the history and current status of neural network studies. It signals some of the essential problems for which answers have to be found before substantial progress in the field can be made. PMID- 2245131 TI - Determinants of nerve cell patterns during development: a review. AB - The aim of the work reviewed is to define some of the mechanisms which are implicated in the control of neural cell pattern formation in the developing central nervous system. This question was examined by studies of brain embryonic development in normal and reeler mutant mice, which are characterized by profuse architectonic anomalies. The adult reeler phenotype is characterized by extreme abnormalities of cell positioning in the telencephalic and cerebellar cortices as well as by distinct architectonic anomalies in non-cortical structures such as the inferior olive, the facial nerve nucleus and other brainstem nuclei. Studies of the embryonic development of these structures reveal that neurons are generated at the normal time and migrate along normal pathways. Moreover, the processes of directional axonal growth, differentiation of class-specific features of neurons and glia, and synaptogenesis appear unaffected by the reeler mutation. In all instances, however, the early cell patterns formed by reeler neurons is consistently less regular than in normal embryos. These data indicate that brain architectonics does not exclusively result from the maturation of cells, neurites and connections, but is also contingent upon a specific stabilization of early neurons at the end of migration. One may infer that the presence of a normal allele at the reeler locus is necessary for this stabilization to occur normally, or that it is submitted to genetic control. Although the factor(s) responsible for the stable configuration of neural cell patterns are still unknown, several hypotheses can be considered. There is ample evidence against the role of diffusible factors, mesodermal components and afferent fiber systems. So far, most data point to the importance of cell-cell interactions which can be of three types: homophilic (neuronal-neuronal), heterophilic (neuronal-glial), or both. The cell-interaction mechanism could have been acquired during brain evolution of the mammalian lineage and the reeler gene could act by perturbing, directly or indirectly, these cell interactions. A better definition of the mechanisms responsible for the organization of nerve cell patterns is central to our understanding of brain development in normal as well as in pathological states. By following the example of recent successful research on invertebrate brain development, we believe that the genetic approach to this important question is a valuable one. PMID- 2245132 TI - Hypertrophy of inferior olivary neurons: a degenerative, regenerative or plasticity phenomenon. AB - After contralateral hemi-cerebellectomy, neurons in the cat inferior olive may either degenerate, appear unchanged (affected) or become hypertrophic. Morphological and physiological aspects of the latter two cell types are studied by means of intracellular recording and injection techniques and compared to normal olivary neurons. It is demonstrated that affected and hypertrophic olivary neurons can be activated by mesodiencephalic stimulation. Affected olivary neurons are morphologically very similar to normal cells. However, they may respond with long latency action potentials only to mesodiencephalic stimulation. Hypertrophic olivary neurons have an enlarged dendritic tree and soma. The soma and proximal dendrites are studded with spine-like processes. Their reaction to mesodiencephalic stimulation is very diverse and may consist of short and/or long latency action potentials that may or may not trigger dendritic spikes. It is argued that olivary hypertrophy does not present either a degenerative or regenerative state, but that both hypertrophic as well as affected olivary neurons can survive axotomy due to a strong and continuous electrotonic coupling, made possible by destruction of the GABAergic cerebellar afferents. PMID- 2245133 TI - Ultrastructural study of the cat hypertrophic inferior olive following anterograde tracing, immunocytochemistry, and intracellular labeling. AB - Contralateral cerebellectomy can induce hypertrophy of olivary neurons in cat. In the present study we examined the ultrastructure of the cat hypertrophic inferior olive following GABA-, dopamine- and serotonin-immunocytochemistry, anterograde tracing from the mesodiencephalic junction, and intracellular labeling with HRP. Compared to normal olivary neurons the hypertrophic cells showed larger cell bodies, more and longer somatic spines which were linked by gap junctions, and longer distal dendrites with relatively few spines. The hypertrophic olivary neurons received less GABAergic boutons on their dendrites but an equal percentage was apposed to their somata as compared to normal cells. Relatively many mesodiencephalic terminals, a similar serotoninergic, and a slightly increased dopaminergic input were found. The axon of one intracellularly labeled hypertrophic cell gave off recurrent collaterals bearing varicosities filled with vesicles. These results indicated that 1) hypertrophic olivary cells are affected by trophic factors not only at the cell body but also at the level of the somatic spines, dendrites, and axon, 2) the ratio of excitatory to inhibitory terminals is increased in the hypertrophic neuropil, whereas the monoaminergic input remains stationary, and 3) the electronic coupling between hypertrophic olivary neurons has shifted from a dendritic to a more somatic location due to a relatively high number of gap junctions between the somatic spines. PMID- 2245134 TI - The rat olivocerebellar system visualized in detail with anterograde PHA-L tracing technique, and sprouting of climbing fibers demonstrated after subtotal olivary lesions. AB - The rat olivocerebellar climbing fiber system has been investigated at the light and electron microscopic level with anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) tracing. From PHA-L Injections in different parts of the inferior olive labelled axons could be traced to the contralateral cerebellum. Arriving in the deep cerebellar white matter, the olivocerebellar axons ran around and through the cerebellar nuclei. Plexuses of labelled terminal fibers appeared in the cerebellar nuclei, and the density of this innervation was estimated to 1-4 million varicosities per mm3. Ultrastructurally, these boutons engaged in asymmetric synapses with small dendrites. Bundles of labelled fibers continued into the folial white matter, and terminated as climbing fibers in sagittal zones of the cerebellar cortex. Both the cortical and nuclear terminations of the olivocerebellar system are strictly topographically organized. The plasticity of climbing fibers was studied after partial lesions of the inferior olive induced by 3-acetylpyridine. One to 6 months after the lesion, surviving climbing fibers demonstrated extensive sprouting. The newly formed axons originated from parent climbing fiber plexuses, grew in the direction of parallel fibers, and formed terminal plexuses around several neighbouring Purkinje cells. As normal climbing fiber terminals, these terminals formed asymmetric synapses with spines of proximal Purkinje cell dendrites, and evidence by Benedetti et al. (1983) shows that the regenerated innervation is electrophysiologically functional. It is suggested that denervated Purkinje cells release a trophic substance, which stimulate surviving climbing fibers to sprouting, axonal growth and synapse formation. PMID- 2245135 TI - The neurofilament architecture of the rat suprachiasmatic nucleus. AB - The neurofilament architecture within the suprachiasmatic nucleus of the rat was analyzed immunocytochemically using neurofilament monoclonal antibodies. The topographic distribution of neurofilament containing structures was restricted mainly to the ventral and caudal part of the suprachiasmatic nucleus, coinciding with the entrance area of the retino-suprachiasmatic fibres of this nucleus. Within the nucleus itself an axonal organization was present. The axons were grouped, forming clusters. These clusters existed of a core of myelinated axons surrounded by unmyelinated axons. The myelinated/unmyelinated axon ratio could reach 1:25. Within the nucleus the myelinated axons extended upwards to the middle part of the suprachiasmatic nucleus, where the fibers of the axon clusters fanned out. PMID- 2245136 TI - Astrocyte-mediated induction of alkaline phosphatase activity in human umbilical cord vein endothelium: an in vitro model. AB - The blood-brain barrier, localized in the endothelium of the cerebral capillaries, is characterized by the existence of tight junctions, a low mitochondrial density, a low number of vesicles and a high activity of certain enzymes like alkaline phosphatase and gamma-glutamyl transpeptidase. Astroglial cells secrete a product that induces brain microvessel endothelial cells to differentiate into endothelial cells with blood-brain barrier properties. If rat astrocytes were grown together with human umbilical cord vein endothelial cells in a co-culture system in which there is no cellular contact between both cell types, alkaline phosphatase activity was induced in the endothelial cells after three days of co-culturing. If the endothelial cells were cultured in astrocyte conditioned medium, alkaline phosphatase activity was also induced, and preliminary results showed that formation of tight junctions occurred after five days. These observations support the hypothesis that astrocytes induce the differentiation of non-blood-brain barrier endothelial cells into endothelial cells with blood-brain barrier properties, in this study based on alkaline phosphatase-activity induction and induction of tight junction formation. These inductive processes are produced by a soluble factor released by the astrocytes. PMID- 2245137 TI - The central control and ontogeny of circadian rhythmicity. AB - The field of Chronobiology, the study of the rhythms in plants and animals, was restricted to botanists for centuries. Only recently during the last decades research could be broadened to include animals and later even human beings. Rhythms have been documented and related to the alternation of day and night and to the succession of the seasons. Nowadays chronobiology has developed into a multidisciplinary field in which scientists are involved in basic research as well as in applied topics. This paper gives an introduction to the field, especially dealing with the aspect of rhythm development and the way in which the different 24 hour rhythms in children become apparent. PMID- 2245138 TI - Physiological basis for photic entrainment. AB - The suprachiasmatic nuclei of the hypothalamus contain a major circadian pacemaker. The most important external stimulus that affects the circadian pacemaker is the environmental light-dark cycle. The effects of light and darkness on the pacemaker at various phases of the circadian cycle have been well documented. In this paper these effects are summarized briefly. A number of pharmacological and neurophysiological studies will then be presented that are related to the processing of light information by the circadian system. It will be considered whether these studies have increased insight in the behavioral responsiveness to light. PMID- 2245139 TI - The suprachiasmatic nucleus of the rat hypothalamus in culture: an anatomical and electrophysiological study. AB - This study shows that foetal neurons from the suprachiasmatic area, after dissociation and culture, contain in vitro the same characteristics as are found in the in vivo situation. The main peptidergic neurotransmitters present in the suprachiasmatic nucleus in vivo, vasoactive intestinal polypeptide (VIP) and vasopressin, are expressed in vitro while the cytoskeleton of these cells possesses phosphorylated neurofilaments. The exclusive uptake of Lucifer Yellow liposomes by neurons is also refound in suprachiasmatic cultures. The electrophysiological results are in agreement with those characteristics found in vitro and in vivo. PMID- 2245140 TI - Developmental and functional aspects of grafting of the suprachiasmatic nucleus in the Brattleboro and the arrhythmic rat. AB - The development of suprachiasmatic nuclei (SCN) dissected from fetal rats and grafted in adult rat brains has provided additional insights in the normal ontogeny of the SCN. The SCN survives rather easily and develops to its typical adult cytoarchitectonical arrangement of contiguous clusters of vasopressin (VP) , vasoactive intestinal polypeptide (VIP)- and somatostatin (SOM)- immunoreactive cells. Neither site of implantation, nor the establishment of efferent or afferent connections of the grafted SCN seems to be essential to allow it to develop normally into this distinguishing cytology. This independent maturation does certainly not contradict with its known endogenous and independent potency of circadian pacemaker function in the brain. If the fetal SCN is grafted in such a way that it could merge with the parenchyma of the brain of a VP-deficient Brattleboro rat, the VP neurons of the SCN often establish efferent connections with the genuine target areas of this nucleus as could be shown immunocytochemically. When the fetal SCN is grafted homotopically in the brain of SCN-lesioned rat (or hamster), the surviving SCN neurons are able to reverse the arrhythmicity of these rats. Free-running circadian rhythm of drinking or motor behaviour in constant darkness are induced within weeks after grafting. A correlation between this restorative effect and the immunocytochemical staining pattern of the SCN in the transplant and/or the afferent and efferent connections between graft and host brain, could, however, not be shown conclusively. Transplants with surviving SCN are also seen when arrhythmicity was still present, which made us conclude that there has to be a neural connection between graft and host rather than a neurohumoral control in order to explain the restorative effect of the SCN graft in SCN-lesioned animals. PMID- 2245141 TI - Some aspects of the neuronal cytoskeleton in development. AB - The review is focused on developmental aspects of the neuronal cytoskeleton, its molecular composition and the intracellular distribution of its elements. It includes a survey of the molecular properties of several cytoskeletal proteins such as tubulins, microtubule-associated proteins, neurofilament subunits, actins and brain spectrins. Furthermore it is addressed how microtubules, neurofilaments, microfilaments and the spectrin-based membrane cytoskeleton are involved in the generation of the neuronal cytoarchitecture, and how changes in the molecular composition of the cytoskeleton during the differentiation process of a neuron may correlate with cell function. PMID- 2245142 TI - Acetylcholinesterase in the developing rat spinal cord: an enzyme histochemical study. AB - A descriptive enzyme histochemical study on the expression of acetylcholinesterase (AChE) in the developing rat spinal cord is presented. Between E11-E16, AChE was found to be associated with premitotic neurons of the ventral matrix layer, which indicated an involvement in the proliferation of the spinal cord motor neurons. From E12 on, AChE was abundantly present in the motor neurons of the ventral mantle layer, and in their fibres. This early expression suggested a function of AChE in the development of the motor neurons, rather than an active role in cholinergic transmission. The intermediolateral, the intermediomedial cell column and the region between these cell groups, were found to be positive for AChE. Cells of the adult intermediolateral cell column also expressed AChE. AChE, therefore, apparently plays a role in the development as well as in the functioning of the rat autonomic system. In the lateral funiculus, cells of the lateral spinal nucleus expressed AChE. After P8, AChE was expressed in the substantia gelatinosa. The enzyme may be associated with the fibre terminals of the primary afferents. AChE was found to be temporary expressed in the developing dorsal funiculus, which suggested a function of the enzyme in fibre growth and path-finding. At E12, AChE was located in the ventral aspect of the dorsal root ganglion. Later on, AChE positive cells were found throughout the ganglion. PMID- 2245143 TI - Enzyme histochemistry of the spinal cord after experimental transection (Th 9) in the cat. AB - Subpial complete resection of a 10 mm segment of the spinal cord at Th 9 was performed in 9 adult cats. Topographic enzyme histochemical investigations of the terminal clubs were performed after different survival times after transection in 7 cats and three days after a subsequent one-week-delayed autologous sciatic grafting procedure in the remaining two cats. For acid phosphatase (ACP), the count of active terminal clubs was high (200 per m2) from 12 hours until day 3 after transection. Then the count of active terminal clubs decreased to a low level (20 per m2) and remained the same until day 14. Removal of necrotic tissue and subsequent grafting with autologous sciatic nerve did not change these findings. For succinate dehydrogenase (SDH), the numbers of terminal clubs showed the same pattern at a lower level. The SDH defined terminal clubs were smaller than the ACP ones. The length of the SDH positive area decreased after 7 days while the ACP positive area remained the same until day 14. The SDH active terminal clubs are overgrown by the ACP positive terminal clubs, after the 7th day. Considering that SDH is linked to constructive activity in mitochondria and ACP to destructive activity in lysosomes, this phenomenon might be responsible for the termination of the capacity of the spinal cord tissue to regenerate. PMID- 2245144 TI - Morphological and functional properties of rat dorsal root ganglion cells cultured in a chemically defined medium. AB - A culture procedure for dorsal root ganglion (DRG) cells is presented using a completely defined culture medium without antibiotics, in combination with mechanical dissociation procedures. This culture procedure allows all dorsal root ganglion cell types to be cocultured for periods of at least 106 days. Some of the dorsal root ganglion neurons, which could be identified by their neurofilaments and the presence of fluoride resistant acid phosphatase, regained their original T-cell appearance within two weeks. After one month in culture ganglion-like reaggregates appeared. Schwann cells, satellite cells and fibroblasts were identified using morphological criteria. All neurons tested maintained excitability during, at least, the first 35 days in culture, since in all cases action potentials could be evoked by current pulses. The method has proved to be useful in the study of morphological, cytochemical and electrophysiological aspects of dorsal root ganglion cell differentiation in vitro. PMID- 2245145 TI - Musculoskeletal trauma: management and complications. PMID- 2245146 TI - Manifestations of systemic disease and infections of the musculoskeletal system. PMID- 2245147 TI - Imaging of joint and soft-tissue disorders. PMID- 2245148 TI - Imaging of spinal disorders. PMID- 2245149 TI - Magnetic resonance imaging in the evaluation of the solitary tumor of bone. PMID- 2245150 TI - Surgery in the musculoskeletal system, including endoprosthesis and internal fixation. PMID- 2245151 TI - Miscellaneous reports of interest in musculoskeletal radiology. PMID- 2245152 TI - Mammographic image receptors and image processing. PMID- 2245153 TI - Strategies for more effective delivery of mammography screening services. PMID- 2245154 TI - Mammography of the altered breast. PMID- 2245155 TI - Mammographically guided fine-needle aspiration cytology of nonpalpable breast lesions. PMID- 2245156 TI - Magnetic resonance imaging and spectroscopy of the breast. PMID- 2245157 TI - Musculoskeletal radiology. PMID- 2245158 TI - Breast. PMID- 2245159 TI - Conformal therapy. PMID- 2245160 TI - Morphine: pharmacokinetics and clinical practice. PMID- 2245161 TI - Clustering and Hodgkin's disease. PMID- 2245162 TI - Reversal of acquired resistance to adriamycin in CHO cells by tamoxifen and 4 hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein. AB - Tamoxifen and 4-OH tamoxifen were used to reverse multidrug resistance (MDR) in CHO cells with acquired resistance to adriamycin (CHO-Adrr). Because alpha 1 acid glycoprotein (AAG) can bind a range of calcium channel blockers that also reverse MDR and rises in malignancy, its interactions with tamoxifen and 4-OH tamoxifen were also studied. Tamoxifen decreased the IC50 of 10 microM adriamycin 4.8-fold in the parent CHO-K1 cell line and 16-fold in CHO-Adrr. Similarly 4-OH tamoxifen decreased the IC50 3-fold in the parent cells, but 13-fold in the resistant cells. Tamoxifen and 4-OH tamoxifen were similarly potent in reversing MDR, although their anti-oestrogen potency differs 100-fold. AAG was added in increasing concentrations to the combination of adriamycin and tamoxifen. As AAG concentrations increased from 0.5 to 2 mg ml-1 (the range found in vivo) the effect of tamoxifen on reversing MDR was gradually decreased. At the highest AAG concentrations, there was complete reversal of the effects of both tamoxifen and 4-OH tamoxifen. AAG was found to bind 3H-tamoxifen in a non-saturable non specific manner, in contrast to the binding of tamoxifen to albumin. Thus the use of tamoxifen as a reversal agent for MDR in vivo may be impaired by high binding to AAG. However, at the lower range of normal values of AAG, there was still an effect of 10 microM tamoxifen. It may be desirable to select patients for modifier studies based on AAG plasma levels. PMID- 2245163 TI - Effect of tumour necrosis factor and lipid A on functional and structural vascular volume in solid murine tumours. AB - Effects of recombinant tumour necrosis factor (TNF) on functional and structural vascular volumes in solid murine Meth A tumours were investigated by injection of Hoechst 33342 and staining for the vascular basement membrane component laminin, respectively. Systemic injection of 3 x 10(4) U TNF caused an initial increase in functional volume in the tumour, but a strong decrease from 1 to 48 h after treatment. Early effects of intralesional treatment were more moderate. Systemic injection of 10(4) U TNF or 0.3 or 3 micrograms lipid A caused a fall in functional volume at 4 h, but a recovery was seen at 24 h. This recovery did not occur after treatment with a combination of 10(4) U TNF and 0.3 micrograms lipid A. Structural vascular volume was not markedly reduced until 24 h after treatment with the high doses of the separate agents and the combination. All effects appeared generally more prominent in the tumour centre than in the borders. Data suggest that TNF induces initially an active hyperaemia that rapidly converts to passive hyperaemia. A prolonged disturbance of tumour blood supply is probably necessary for therapeutic activity. Breakdown of laminin in the vascular basement membrane may be a cause of loss of vascular integrity. PMID- 2245164 TI - Low density lipoprotein for delivery of a water-insoluble alkylating agent to malignant cells. In vitro and in vivo studies of a drug-lipoprotein complex. AB - Previous studies have shown that human leukaemic cells and certain tumour tissues have a higher receptor-mediated uptake of low density lipoprotein (LDL) than the corresponding normal cells or tissues. LDL has therefore been proposed as a carrier for anti-cancer agents. In the current study, a water-insoluble mitoclomine derivative (WB 4291) was incorporated into LDL. The WB 4291-LDL complex contained about 1,500 drug molecules per LDL particle and showed receptor mediated toxicity in vitro as judged from the difference in growth inhibitory effect on normal and mutant (LDL-receptor-negative) cultured Chinese hamster ovary cells. However, cellular drug uptake did not exclusively occur by the receptor pathway since mutant cells were also affected to some extent. The LDL part of the complex had the same plasma clearance and organ distribution as native LDL after i.v. injection in mice and rabbits. Therapeutic effects were observed when Balb-C mice with experimental leukaemia were treated with the complex. After i.p. administration to mice with i.p. leukaemia median survival time was prolonged 2.5-fold and 40% became long time survivors. The effect was weaker (42% increase in life span) after i.v. injections of the complex to mice with i.v. leukaemia. PMID- 2245165 TI - Biochemical and pharmacological consequences of the interaction between methotrexate and ketoprofen in the rabbit. AB - Severe methotrexate (MTX) toxicity is a proven complication of associations of MTX and non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated the interaction between MTX (50 or 100 mg kg-1) and ketoprofen (KP) (3 mg kg-1 day-1, pretreatment for 8 days) in the rabbit. The drug association induced a reversible increase in blood urea and creatinine. The severity degree of renal dysfunction was significantly related to the MTX dose; it was not modified by prolonged exposure to KP after MTX administration. The biological markers of haematopoietic and hepatic functions were unchanged. Pretreatment by KP induced a marked reduction (70%) in the urinary excretion of the prostaglandin 6-keto-PGF1 alpha. MTX dose-related alterations in MTX pharmacokinetics were also observed with the drug association: at a MTX dose of 100 mg kg-1, the presence of KP significantly reduced the total body clearance, the renal clearance and the fraction of MTX eliminated in urine as compared to controls. An appreciable reduction in the plasma binding of MTX was also noted in vivo when KP was associated. This experimental study confirms the existence of an interaction between MTX and KP and demonstrates its renal origin. PMID- 2245166 TI - Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids. AB - Seventy-five nude mice received subcutaneous inoculation with 1 X 10(7) cells of the human colonic cancer cell lines COLO-320 or HT-29. Tumour growth was assessed over 4 weeks in animals given one of three iso-caloric diets; standard diet, high saturated fat (20% coconut) diet and high n-3 fat (20% Maxepa fish oil) diet. The n-3 diet produced significant tumour growth reduction compared to the other diets for COLO-320 at 3 to 4 weeks (P less than 0.05 at least) and similarly for HT-29 at 4 weeks (P less than 0.05). Significant incorporation of n-3 fatty acids occurred in red cell membranes, adipose tissue and both neutral lipid and phospholipid fractions of tumour lipids in animals fed Maxepa (P less than 0.01 at least). This was accompanied by reduction of linoleic acid and arachidonic acid in these tissues (P less than 0.01 at least) but was most marked in the metabolically labile phospholipid fraction. There was high mitotic activity in the tumours from all the groups but there was no difference according to diet. PMID- 2245167 TI - Ha-ras gene codon 12 mutation and DNA ploidy in urinary bladder carcinoma. PMID- 2245168 TI - Pharmacokinetic studies with the antifolate C2-desamino-C2-methyl-N10-propargyl 2'-trifluoromethyl-5,8-dideazafolic acid (CB3988) in mice and rats using in vivo 19F-NMR spectroscopy. AB - In vivo 19F-NMR spectroscopy has been used to study the pharmacokinetics of the experimental antifolate drug CB3988 (C2-desamino-C2-methyl-N10-propargyl 2'trifluoromethyl-5,8-dideazafolic acid) in mice and rats. NMR results have been compared to those obtained by HPLC and the effect of the inclusion of the CF3 group evaluated by comparing the pharmacokinetics of CB3988 and ICI 198583 (C2 desamino-C2-methyl-N10-propargyl-5,8-dideazafolic acid) in rats. In mice, following the administration of CB3988 (500 mg kg-1 i.v.), drug could be detected in both the upper and the lower abdomen. NMR signal from the upper abdomen reached maximum intensity 10-40 min after administration, declining thereafter with a half life of 28 min. Signal detected in the lower abdomen reached maximum intensity 60-90 min after treatment. HPLC analyses indicated that CB3988 was present at appreciable concentrations (about 20-30 mg ml-1) in both bile and urine which is consistent with the signal from the upper and lower abdomen being derived from the gall bladder and urinary bladder, respectively. Studies in rats also indicated that CB3988 (100 mg kg-1 i.v.) rapidly entered and was cleared from the upper abdomen. Comparison of data from rats with intact and cannulated bile ducts suggested that 19F-NMR could detect CB3988 undergoing enterohepatic circulation. Furthermore, comparison of the plasma half life of CB3988 with the half life for the decline of the NMR signal from the upper abdomen suggested that NMR measurements may reflect the plasma clearance of CB3988. When the pharmacokinetics of CB3988 and ICI 198583 were compared the only significant difference was in the alpha phase half life which was 2-fold faster for CB3988. These data demonstrate that CB3988 is cleared rapidly by both biliary and urinary excretion. This is in contrast to N10-propargyl-5,8-dideazafolic acid, where delayed excretion is associated with hepatic and renal toxicities. The ability to study CB3988 pharmacokinetics non-invasively by 19F-NMR spectroscopy confirms the utility of the technique and, since 19F-NMR can be applied directly to clinical investigations, it may be possible to obtain similar information in humans. PMID- 2245169 TI - Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo. AB - The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation. PMID- 2245170 TI - Ras oncogene expression and DNA content in plasma cell dyscrasias: a flow cytofluorimetric study. AB - Using bivariate flow cytofluorometry, we have determined the nuclear DNA distribution and the expression of the p21 protein (coded by the Ha-ras oncogene) in the bone marrow (BM) cells of five solid tumour patients having histologically normal BM and in those of 57 patients with plasma cell dyscrasia (28 with monoclonal gammopathies of undertermined significance, MGUS, and 29 with multiple myeloma, MM). All normal and MGUS and 21/29 (72.4%) MM BM had diploid modal DNA content and 8/29 (27.6%) MM BM had both diploid and hyperdiploid cell populations. In normal and MGUS BM, the level of the p21 oncoprotein was low and uniform in all G0/G1, S and G2 cells (median fluorescence values in arbitrary units were 6.1 and 7.5, respectively). The level of p21 was increased both in different aliquots of G0/G1 cells and in the S and G2 cells in diploid MM (median value for G0/G1 cells was 20), and especially in MM with hyperdiploid clones (median value for hyperdiploid cells was 40.5, P less than 0.005 with respect to normal and MGUS BM and less than 0.005 with respect to diploid MM BM). The p21 expression was greater in patients with advanced (stage III) than in earlier MM (stages I + II) (P less than 0.005), and it was directly related to the BMPC infiltration (r = 0.7; P less than 0.005). Since p21 expression is greater in MM than in both normal and MGUS BM, Ha-ras could be involved in the malignant plasma cell transformation that distinguishes MM from MGUS. PMID- 2245171 TI - Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels. AB - The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level. PMID- 2245172 TI - The radiation dose-rate effect in two human neuroblastoma cell lines. AB - The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requirement for further information on the radiobiology of these cells. Here we report on studies of the dose-rate effect in two human neuroblastoma cell lines (HX138 and HX142) and the recovery that they demonstrate in split-dose experiments. The sensitivity of the two cell lines to high dose rate irradiation was confirmed. Surviving fractions at 2 Gy were 0.083 for HX138 and 0.11 for HX142. There was little evidence of a dose-rate effect above 2 cGy min-1 but significant sparing was seen at lower dose rates. Substantial recovery was seen in split-dose experiments on both cell lines, to an extent that was consistent with the linear quadratic equation. The data were used to derive values for the beta parameter of the linear-quadratic equation; the values for the neuroblastomas were higher than for any of the other human tumour cell lines that we have investigated to date. Thus, despite their high sensitivity to ionising radiation HX138 and HX142 do exhibit substantial levels of cellular recovery, suggesting that they may have a significant capacity for repair of radiation-induced lesions. PMID- 2245173 TI - Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. AB - The possibility that weight loss in cancer patients may be augmented by tumour produced catabolic factors, which stimulate lipid mobilisation, was investigated in a group of cancer patients with total body weight loss ranging from 0 to 50%. The serum and urine lipolytic activity has been determined using freshly isolated murine adipocytes in an in vitro assay. As a control group, we have used patients with Alzheimer's disease, in which some patients may lose a considerable amount of weight, without an obvious cause. The serum lipolytic activity for the Alzheimer's group with weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1 serum) was not significantly different from the group without weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1) or from a healthy control group (0.07 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1), but all three groups were significantly (P less than 0.005) lower than the cancer patient group (0.20 +/- 0.03 mumols glycerol 10(5) adipocytes-1 ml-1), irrespective of weight loss. A similar difference between the cancer and the control group was observed for the urinary lipolytic activity (0.67 +/- 0.03 versus 0.28 +/- 0.03 mumols glycerol released 10(5) adipocytes-1 mg creatinine-1 respectively, P less than 0.01). Weight loss in animals bearing the MAC16 adenocarcinoma was paralleled by a corresponding rise in serum lipolytic activity which peaked when the loss of carcass weight was 16%. A similar decrease in serum lipolytic activity was also observed in cancer patients at high percentages loss in body weight. However, a linear relationship was observed between both the serum and urinary lipolytic activity and weight loss in cancer patients (correlation coefficients 0.79 and 0.70 respectively) when the total body weight loss did not exceed 20%. This suggests that weight loss in cancer patients may be attributed, at least in part, to an, as yet, unidentified lipolytic factor. PMID- 2245174 TI - Alterations in serum lipolytic activity of cancer patients with response to therapy. AB - The effect of chemotherapy on the serum lipid mobilising activity of a group of cancer patients with or without weight loss has been determined. The pre treatment level of serum lipolytic activity in all cancer patients, with or without weight loss, was higher than normal controls (0.22 +/- 0.01 versus 0.06 +/- 0.01 mumols glycerol released ml-1 serum respectively). The pre-treatment levels of lipid mobilising activity in the patients serum was proportional to the extent of weight loss (correlation coefficient 0.81), if the extent of weight loss was small (less than 14 kg). Patients who showed a positive response to chemotherapy also showed a decrease in their plasma levels of lipolytic activity, while a patient who showed no response to therapy also showed no change in the serum lipolytic activity. There was no correlation between the serum lipolytic activity and response to megestrol acetate, a synthetic orally active progestogen, which is currently under investigation as an anticachectic agent. Serum from cancer patients showed lipolytic activity which was retained on a DEAE cellulose column and eluted by a salt gradient, in contrast with normal controls. Response to chemotherapy was associated with a decrease of the retained material, although the profile did not return to the normal state. These results need confirmation in a larger group of patients using more specific methods to determine tumour lipolytic activity, but suggest that it may be possible to monitor response to therapy by measurement of the serum lipolytic activity. PMID- 2245175 TI - Cell kinetics: an independent prognostic variable in stage II melanoma of the skin. AB - The prognostic role of cell kinetics (expressed as 3H-thymidine labelling index, 3H-TdR LI) was assessed on 145 patients with pathologic stage II melanoma subjected only to therapeutic lymph node dissection. The 3H-TdR LI determined on metastatic nodes was related to relapse-free survival and to survival. In particular, 3-year relapse-free survival was significantly different from patients with slowly and rapidly proliferating melanomas (40% vs 22%, P = 0.007), and this finding was consistently found for overall survival (68% vs 46%, P = 0.007). Moreover, in patients with high 3H-TdR LI tumours, the risk of relapse and death within the first year from lymphadenectomy was two-fold that of patients with low 3H-TdR LI tumours. Multiple regression analysis showed that 3H TdR LI retained its prognostic significance on relapse-free and on overall survival even when the number of involved nodes and type of nodal metastases were considered. Present findings suggest that 3H-TdR LI can contribute to select high risk stage II melanoma patients. PMID- 2245176 TI - High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study. AB - In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity. PMID- 2245177 TI - Serum interleukin-2 levels in relation to the neuroendocrine status in cancer patients. PMID- 2245178 TI - Clinical pharmacokinetics of etoposide during 120 hours continuous infusions in solid tumours. PMID- 2245179 TI - A population-based case-control investigation on cancers of the oral cavity in Bangalore, India. AB - A case-control study on cancers of the oral cavity was conducted by utilising data from the population based cancer registry. Bangalore, India. Three hundred and forty-eight cases of cancers of the oral cavity (excluding base tongue) were age and sex matched with controls from the same residential area but with no evidence of cancer. The relative risk due to pan tobacco chewing was elevated in both males and females, being appreciably higher in the latter (relative risk 25.3%; 95% confidence interval 11.2-57.3). A statistically significant (linear test for trend P less than 0.001) dose response based on years, times per day and period of time chewed was seen. Any smoking (cigarette or bidi or both) had only slightly elevated risk of developing oral cancer, whereas a history of alcohol drinking or inhalation of snuff did not influence the risk. A new finding of our study was the markedly elevated risk of oral cancer in persons consuming ragi (Eleusine coracana, family graminae) in comparison to those not consuming ragi as staple cereal in their diet. There also appeared to be some interaction between ragi consumption and tobacco chewing with substantially higher relative risks in those who pursued both habits compared to those who gave a history of either. PMID- 2245180 TI - The influence of tumour cell DNA content on survival in colorectal cancer: a detailed analysis. AB - We have investigated the influence of tumour cell DNA content (ploidy) on survival of 416 patients undergoing excisional surgery for colorectal cancer. Two hundred and eleven (51%) tumours had an abnormal DNA content (aneuploid or tetraploid). There was no correlation between ploidy status, sex, age and pathological stage, histological grade, tumour site, local tumour extension or assessment of curability. Patients with tumours with an abnormal DNA content had a poorer survival 68/211 (32%) than patients with near normal (diploid) DNA content 88/205 (43%) (test statistic 5.0, P = 0.02). The patient subgroups in which DNA content exerted an influence on survival were: stage B tumours (P = 0.0058), moderately differentiated tumours (P = 0.004), rectal tumours (P = 0.02), and mobile tumours (P = 0.02). Multivariant analysis showed that pathological stage, local tumour extension and DNA ploidy were all independent prognostic indicators whereas histological grade, tumour site and assessment of 'curability' were not. The influence of pathological stage, however, was much greater than that of local tumor extension or DNA ploidy. Tumour cell DNA content together with pathological stage and local tumour extension may be used in a prognostic index and may be important in planning adjuvant therapy. PMID- 2245181 TI - Prognostic factors for survival in soft tissue sarcoma. AB - Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters. PMID- 2245182 TI - Oncofetal markers CA 19-9, CA 125 and SP1 in healthy children and in children with malignancy. PMID- 2245183 TI - Testicular cancer trends in the Canton of Vaud, Switzerland, 1974-1987. PMID- 2245184 TI - An attempted suicide when hypoglycaemic. PMID- 2245185 TI - Cancer risks in painters: study based on the New Zealand Cancer Registry. AB - Painters are exposed to a range of complex chemical mixtures which include organic solvents and dye products with known carcinogenic and mutagenic potential. Trade painters or those manufacturing paints and coatings have increased rates of non-malignant diseases and cancers; including lung cancer, acute leukaemia, bladder cancer, and cancers of the oesophagus, larynx, biliary system, liver, skin, and large bowel. A series of case-control studies of painters, based on the New Zealand Cancer Registry, are presented. These concerned 19,904 male patients registered for the period 1980-4 who were aged 20 or older at the time of registration. For each cancer site studied, the registrants for all other cancer sites formed the control group. Three cancer sites were associated with work as a painter--namely, bladder tumours (odds ratio (OR) 1.52, 95% confidence interval (95% CI) 1.00-2.31), kidney and other urothelial tumours (OR 1.45, 95% CI 0.85-2.50), and multiple myeloma (OR 1.95, 95%, CI 1.05-3.65). Risks for multiple myeloma were greater among car or spray painters and signwriters (OR 2.81) compared with construction and general painters (OR 1.80). No increased risk was found for leukaemia or for respiratory, biliary, skin, or gastrointestinal cancers. PMID- 2245186 TI - Six year follow up of lung function in men occupationally exposed to formaldehyde. AB - The long term effects of formaldehyde on the respiratory tract have been investigated in a group of 164 workers exposed daily to the chemical during the production of urea formaldehyde resin, together with 129 workers not exposed to free formaldehyde. Exposure was classified as high (corresponding to an eight hour time weighted exposure of more than 2.0 ppm), medium (0.6 to 2.0 ppm), or low (0.1 to 0.5 ppm). Twenty five per cent of workers had had high exposure at some time and 17% moderate exposure. Both the exposed and unexposed groups had an annual assessment that included lung function. The proportion with self reported respiratory symptoms was similar in the two groups, 12% and 16% reporting breathlessness on hurrying and 26% and 20% wheezing. The initial forced expiratory volume in one second (FEV1) was within 0.5 l (approximately one standard deviation (SD)) of the predicted value (by age and height) in 65% of the exposed and 59% of unexposed workers and more than 0.5 l below the predicted value in 9% of exposed and 11% of unexposed workers. The mean decline in FEV1 was 42 ml a year (SD 45) in the exposed group and 41 ml a year in the unexposed group (SD 40 ml a year). The rate of decline showed the expected association with smoking in the unexposed group, but in the exposed group the mean rate of decline in the never smokers was similar to that in current smokers. There were, however, relatively few never smokers and considerable variation in the rates of decline. In the exposed group no association was found between the rate of decline and indices of exposure to formaldehyde. Thus there is no evidence from this study of an excess of respiratory symptoms or decline in lung function in the workers exposed to formaldehyde. The similar rate of decline of FEV1 however in never smokers and smokers of the exposed group is consistent with findings of other studies for workers exposed to formaldehyde and to toluene di-isocyanate. PMID- 2245187 TI - A cohort mortality study and a case-control study of workers potentially exposed to styrene in the reinforced plastics and composites industry. AB - The cohort consisted of 15,908 men and women who worked for at least six months between 1948 and 1977 in 30 participating manufacturing plants in the reinforced plastics and composites industry. These workers were occupationally exposed to the working environment in the industry, which included exposure to styrene. Cause specific mortality analyses were performed based on the standardised mortality ratio (SMR) with the United States population as a comparison. No significant excess of cause specific mortality was found for the total cohort. Mortality from cancer was slightly less than expected (SMR = 88.1). For cancer of the respiratory system, a small non-significant excess was detected (SMR = 116.1). For lymphatic and haematopoietic cancer, a non-significant deficit was found (SMR = 73.3). The observed mortality from leukaemia was similar to that expected (five observed v 4.76 expected deaths). The plants with hot processes (injection moulding, centrifugal casting, compression moulding, continuous lamination, and pultrusion) experienced a significantly increased SMR (177.9) for respiratory cancer, which was more than twice that (78.3) for those with cold processes (resin mixing, lay up and spray up, bag moulding, and filament winding). As potential exposure to styrene from hot processes is considerably less than that from the cold processes, this finding could not be attributed to occupational exposures. A subsequent nested case-control study consisting of 40 cases of deaths from respiratory cancer was conducted. Further information on detailed work history, occupational exposures, and smoking history was collected. The case-control study did not show any significant association between respiratory cancer and direct exposure to styrene (contained in polyester resins), duration of exposure to styrene, the type of process (hot or cold), or whether a resin was used. A statistically significant association (relative risk = 7.33) was found between cigarette smoking and respiratory cancer among the study subjects. PMID- 2245188 TI - Trends and geographical patterns of pleural mesotheliomas in the Netherlands 1970 87. AB - The sex and age related trends and geographical distribution of asbestos related mortality from pleural mesothelioma in the Netherlands between 1970 and 1987 were investigated. Deaths from pleural malignancies recorded by the Dutch Central Bureau of Statistics (CBS) were used and death rates were age adjusted per year by the indirect method. Standardised mortality ratios (SMRs) were computed for 43 regions over the period 1979-86. For men, total mortality increased from 10.8 per million in the period 1970-8 to 20.9 per million during 1979-87. The highest mortality occurred in the group aged between 65 and 74 with 147.7 per million in 1987. The death rate for the group aged between 55 and 64 was 96.5 per million in 1987. For women, total death rates for pleural mesothelioma showed a moderate increase from 2.5 per million in the period 1970-8 to 3.6 per million during 1979 87. The highest mortality occurred in the group aged over 65, fluctuating around 10-15 per million. For men and women under 45 mortality was very low and presented no upward trend. The geographical distribution over the country for the period 1979-86 showed a pattern with a clear concentration of deaths from mesothelioma in men, in conurbations with many harbours, shipyards, and heavy industry near the river mouths and along the North Sea Coast. PMID- 2245189 TI - Pneumomediastinum: a complication of exposure to bromine. PMID- 2245190 TI - Cervical spondylotic radiculopathy precipitated by decompression sickness. PMID- 2245191 TI - Suicide among electric utility workers in England and Wales. PMID- 2245192 TI - Mortality among workers potentially exposed to epichlorohydrin. PMID- 2245193 TI - Asbestos: a chronology of its origins and health effects. PMID- 2245195 TI - Glomerulonephritis, renal carcinoma, and solvent exposure: bias from choice of referents. PMID- 2245194 TI - Blood lead concentration, renal function, and blood pressures in London civil servants. PMID- 2245196 TI - Tom Main (1911-1990). PMID- 2245197 TI - Concerning knowledge of mental states. AB - How does a child acquire knowledge that other people are subjects of experience, and come to differentiate amongst mental states? In this paper I review some philosophical perspectives on these matters. In order to illustrate how the arguments have contemporary relevance, I criticize the 'theory of mind' approach currently favoured by many psychologists and point out certain implications for our view of early childhood autism. PMID- 2245198 TI - Interpreting mood scores: clinical implications of individual differences in mood variability. AB - Mood variability is shown to be a stable characteristic of individuals, such individual differences accounting for some 25 per cent of the total variability of mood scores over time. This large effect is shown to have three major consequences: it is impossible to use tables of norms to assess the severity of a given mood for an individual; the whole logic of using norms for the interpretation of moods is flawed; and correlations between moods and traits have been underestimated in the literature. Various techniques are discussed for minimizing the effects of bias caused by individual differences in mood variability. PMID- 2245199 TI - Women's first experiences of childbirth: two hospital settings compared. AB - This study analyses expectations, experiences and the aftermath of childbirth from interviews conducted with 60 mothers nine months after their first child was born. Half had given birth in a 'family birthing centre' (FBC) and half had used the conventional delivery suite (CDS). Findings showed that the two groups of women had different antenatal orientations to the birth, different experiences of the labour, different experiences of motherhood and different levels of satisfaction with childbirth in retrospect. In particular, women using the FBC wanted to be and were more actively involved in the birth process than women from the CDS, experienced fewer medical interventions during labour and were more satisfied with childbirth afterwards than users of the CDS. FBC mothers reported more breast feeding than bottle feeding at nine months and a greater incidence of self-attributed 'depression'. PMID- 2245200 TI - Transforming identities: a repertory grid case study of the transition to motherhood. AB - This study follows one woman through her pregnancy and the transition to motherhood, exploring the relationship between this life-event and aspects of her personal identity. Repertory grids were obtained from her four times during the transition, and at the end of the study she completed retrospective grids for how she thought she was during the pregnancy. Changes in the grids were analysed and the contemporaneous and retrospective grids compared. The graphical analysis was discussed with the participant. The study finds a growing integration in the woman's personal construct system (both intrapersonal and interpersonal) during the pregnancy. Discrepancies in the woman's retrospective perception were also found, and are discussed in terms of selective self-perception or construction. The woman's reaction to the analysis is included in the paper. The study illustrates a methodology for exploring reflexivity, which is of growing concern in a number of areas of social science. PMID- 2245201 TI - Women's anticipation and experience of childbirth: the independence of fulfillment, unpleasantness and pain. AB - Adjectives or phrases used by women in their description of childbirth were identified by interviewing two groups of 10 women, one drawn from an antenatal clinic, the other following delivery of a healthy child. The terms obtained were formed into a questionnaire on which 106 antenatal women described their expectations of childbirth and 82 postnatal women described their experience. Principal components analysis revealed two important findings. First, the ratings were multidimensional; that is, a dimension of fulfillment and achievement was independent of one of emotional feeling. Second, painfulness was not associated with either dimension. PMID- 2245202 TI - Maternal personality and sex of infant. AB - This study investigated the hypothesis that dominant women are more likely to conceive sons. A Maternal Personality Questionnaire (MPQ) was constructed, using items from Cattell's 16 Personality Factor Questionnaire. Respondents were 85 women, mainly in the first trimester of pregnancy. Those who later bore sons were found to have scored higher on dominance items (p less than .003) than those who later bore daughters. PMID- 2245203 TI - Body image in rheumatoid arthritis: the relevance of hand appearance to desire for surgery. AB - To investigate the importance of body image concerns relating to hand appearance in rheumatoid arthritis, a questionnaire was devised and administered to 80 female out-patients. Subjective judgements of hand attractiveness, feelings about hands, and behaviours relating to hand adornment and concealment were sought. Objective ratings of hand attractiveness were obtained from photographs taken at this time of the women's hands. Factor analysis indicated four principal orthogonal factors describe these body image items. Evaluative and affective elements were found to be independent of each other. The hypothesis that body image, thus rated, is relevant to desire for reparative hand surgery was tested using a two-stage general linear modelling procedure. Body image concerns, particularly negative feelings about hands, emerged as significant predictors of desire for surgery, and remained significant after the removal of variance accounted for by duration of arthritis, age, grip strength and objectively rated hand attractiveness. It is suggested that in rheumatoid arthritis, self perception of hands and the associated emotional response, may be a covert agenda in women's decision to have surgery, and need specific clinical consideration. PMID- 2245204 TI - The in vivo manipulation of alcohol-related beliefs in male social drinkers in a naturalistic setting. AB - Earlier research shows that alcohol expectancies are related to alcohol consumption. However, how the alcohol expectancies are related to drinking in a public bar is still unknown. This paper examines this relationship in 10 moderate heavy male social drinkers attending alternatively to both alcohol dependent and non-dependent cognitive sets of alcohol use. When discussing the alcohol dependent expectancies, these drinkers consumed significantly less alcohol compared with their consumption when discussing non-alcohol dependent expectancies. This group effect was also corroborated by a within-subject analysis of the data. The implications of the relationship between beliefs and drinking behaviour in terms of a cognitive behaviour model of alcohol use are briefly discussed. PMID- 2245205 TI - Authoritarianism as a cause of heart disease: reply to Byrne, Reinhart & Heaven. AB - Byrne, Reinhart & Heaven (1989) report a study which replicates many findings of the present author. They interpret their findings, however, to create the impression that they somehow undermine a theory advanced by the present author. Reasons for this are explored and important omissions are noted. PMID- 2245206 TI - Chlorophyll fluorescence measurements to assess the competition of substituted anthraquinones for the QB binding site. AB - As analogs of the Photosystem II plastoquinone electron acceptor, QB, substituted quinones compete with QB for a common binding domain and thereby inhibit QB function. Substituted quinones interact with the QB binding niche via hydrogen bonds, and the extent of hydrogen bond formation is determined by quinone structure. We have previously shown that the quinone inhibitory activity can be quantitated using measurements of chlorophyll fluorescence quenching. To assess competition for the QB binding site, we report here measurements of the action of various pairs of substituted anthraquinones on the chlorophyll fluorescence emission of barley chloroplasts. The degree of competition between quinones for the QB binding site is classified as competition, partial competition, or no competition. Two quinones were classified as undergoing competition, i.e., interacting for the same or overlapping sites, if the chlorophyll fluorescence level in the presence of the two quinones was not as low as that achieved in the presence of either one of the quinones individually. Non-competitive quinones with different binding sites quenched chlorophyll fluorescence to the level expected if the quenching effects of the individual quinones were additive. Partial competition, or some interaction for the same or overlapping sites, was characterized by an extent of fluorescence quenching in the presence of two quinones that was more effective than either quinone alone but not as sizable as that expected when the two quinones act independently. These results reflect an interesting situation whereby substitution patterns can alter the binding characteristics within a single class of inhibitors. In an accompanying manuscript we report the results of CNDO molecular orbital calculations to demonstrate that the pi charge distribution in substituted quinones governs their binding properties. PMID- 2245207 TI - Analysis of pi charge distribution in substituted anthraquinones to assess affinity for the QB binding site. AB - In the accompanying paper (Biochim. Biophys. Acta (1990) 1020, 163-168), we have determined the degree of competition between substituted 9,10-anthraquinones for the QB binding niche through measurements of the additivity of quinone-quenching effects on chlorophyll fluorescence. Quinones inhibit QB function by competitively displacing QB through hydrogen-bond formation with the QB binding protein. The sign of the net pi-charge density on atoms adjacent to the carbonyl moieties is believed to determine the particular hydrogen-bond(s) that result(s). In this study we report CNDO molecular orbital calculations of pi electronic charge distribution in substituted 9,10-anthraquinones to explore the relationship of inhibitor activity and competition to sign of net pi-charge density. We find that the substitution patterns of 9,10-anthraquinones alter the signs of the net pi-charge densities on the carbon atoms adjacent to the carbonyl moieties and thus determine the binding properties of the anthraquinones in the QB niche. While most experimentally studied 9,10-anthraquinones use both carbonyl oxygens to hydrogen bond to the histidine-215 and serine-264 regions of the D-1 QB binding protein, some quinones appear to hydrogen-bond to only one site. Thus, 9,10-anthraquinones constitute a class of QB inhibitors that function as either members of the histidine or serine family of QB inhibitors or as simultaneous representatives of both inhibitor groups. PMID- 2245208 TI - Regulation of potassium fluxes in Saccharomyces cerevisiae. AB - To investigate the regulation of K+ fluxes in Saccharomyces cerevisiae the dependence of K+ efflux and Rb+ influx on [K+]i, pHi, [Na+]i, membrane potential, cell volume, and turgor pressure were studied in cells with different K+ contents. By decreasing the cell volume with osmotic shocks and the cellular pH with butyric acid the following was found. (1) The K+ efflux induced by uncouplers decreases simultaneously with the decrease of the K+ content of the cell, but the process was insensitive to [K+]i, pHi, cell volume and turgor pressure. The internal presence of Na+ inhibited this K+ efflux. (2) The increase of the Vmax of Rb+ influx observed in low-K+ cells is due to the decrease of the pHi and probably mediated by the increase of the activity of the plasma membrane ATPase. The Vmax is independent of [K+]i, [Na+]i, cell volume and turgor pressure. (3) The decrease in the Km of Bt+ influx observed in low-K+ cells does not depend directly on [K+]i, pHi, cell volume or turgor pressure. If Na+ is present, [Na+]i might be directly involved in the regulation of the Km. PMID- 2245209 TI - Stoichiometries of calcium and strontium transport coupled to ATP and acetyl phosphate hydrolysis by skeletal sarcoplasmic reticulum. AB - The stoichiometries of Ca2+ and of Sr2+ transport by the Ca2(+)-ATPase of skeletal muscle sarcoplasmic reticulum have been previously reported to be 2 and 1, respectively, when determined by flux ratio methods (Mermier, P. and Hasselbach, W. (1976) Eur. J. Biochem. 69, 79-86; Holguin, J.A. (1986) Arch. Biochem. Biophys. 251, 9-16). We have measured transport of Ca2+ and Sr2+ by the pulsed pH-stat method, when supported by ATP or the pseudo-substrate acetyl phosphate (AcP). The stoichiometry of ATP-supported Ca2+ transport, Ca2+/ATP, was pH dependent and varied from 2.0 at pH 6.5 to 1.0 at pH 8.0. Sr2+/ATP ratios showed a similar pH dependence and were approx. 7-18% lower. Ca2+/AcP ratios showed little pH dependence and varied from 2.0 to 1.7 in the pH range 6.5 to 8.0. Sr2+/AcP ratios were 17-34% lower, with maximum differences at the pH extremes. Ruthenium red, which blocks calcium efflux from calcium release channels, increased measured stoichiometries by less than 10%. It is concluded that the transport of both Ca2+ and Sr2+, when supported by either ATP or a pseudo-substrate, have similar stoichiometrics and occurs via identical mechanisms. The relatively low Sr2+ transport ratios have been related to uncoupled reverse flux through the Ca2(+)-ATPase cation transport channel. Subintegral M2+/substrate ratios appear to be an intrinsic feature of active transport by the Ca2+ pump of skeletal muscle sarcoplasmic reticulum. PMID- 2245210 TI - Hemolysis of erythrocytes and fluorescence polarization changes elicited by peptide toxins, aliphatic alcohols, related glycols and benzylidene derivatives. AB - Hemolysis rates of human erythrocytes induced by C2 and C8-C14 straight chain 1 alkanols, 1,2-alkanediols and the corresponding benzylidene derivatives (benzaldehyde acetals) have been studied and compared with hemolysis rates obtained by three peptide toxins. The peak of activity occurs at C12 for the alkanols and glycols and at C10 for the benzylidene derivatives. The most active compound is 1-dodecanol, followed by 1,2-dodecanediol and the C10 benzylidene acetal, which show 50% hemolysis at 15, 99 and 151 microM, respectively, at 37 degrees C. A few lysolecithins and longer chain cis-unsaturated alcohols were studied for comparison purposes, and were found to be more active than 1 dodecanol. The most active were the 16:0 lysolecithin and cis-9-tetradecene-1-ol, which gave 50% hemolysis at concentrations of 2.8 and 5.6 microM respectively. The hemolytic activities of 1-dodecanol, 1,2-dodecanediol and the C10 benzylidene acetal were compared to activities of Pyrularia thionin and melittin with cow, horse, sheep, pig and human erythrocytes. Whereas the peptide toxins showed clear specificity for human erythrocytes, no selectivity was shown by any of the other compounds tested. Addition of the thionin or Naja naja kaouthia cardiotoxin to erythrocyte ghosts caused a slight but reproducible increase in the order of the phospholipid bilayer, as measured with the fluorescent probe NBD-PC. Cardiotoxin gave a greater response than did the P thionin, and extensively iodinated P thionin gave a smaller change than did P thionin. Similar results were obtained with melittin, but this peptide gave a markedly greater response than all other peptides. Addition of dodecanol or the C10 benzylidene acetal caused a marked increase in membrane fluidity. All of these data indicate that the organic compounds interact directly with and are incorporated nonspecifically into the membrane lipid bilayer, but the peptide toxins interact specifically with some component on the surface of the membrane, either a protein or specific phospholipid domain, followed by insertion into the membrane and decreasing phospholipid movement. PMID- 2245211 TI - Orientation into the lipid bilayer of an asymmetric amphipathic helical peptide located at the N-terminus of viral fusion proteins. AB - The complete amino-acid sequence of viral fusion proteins has been analyzed by the Eisenberg procedure. The region surrounding the cleavage site contains a highly hydrophilic region immediately followed by a membrane-like region. Since the effective cleavage between these two domains seems required to expose the fusogenic domain (located at the N-terminal sequence of the transmembrane like region) which is assumed to interact with the lipid membrane of the host cell, we have focused our analysis on the conformation and mode of insertion of this membrane-like domain in a lipid monolayer. It was inserted as an alpha-helical structure into a dipalmitoylphosphatidylcholine (DPPC) monolayer and its orientation at the lipid/water interface was determined using a theoretical analysis procedure allowing the assembly of membrane components. For each viral protein sequence these N-terminal helical segments oriented obliquely with respect to the lipid/water interface. This rather unusual orientation is envisaged as a prerequisite to membrane destabilization and fusogenic activity. PMID- 2245212 TI - The influence of physical characteristics of liposomes containing doxorubicin on their pharmacological behavior. AB - We have investigated the behavior of two populations of doxorubicin (DXR) containing phospholipid vesicles with regard to various physical and pharmacological parameters. DXR-containing liposomes were prepared by ultrasonic irradiation, the lipid composition being phosphatidylglycerol (or phosphatidylserine), phosphatidylcholine and cholesterol. The vesicles were fractionated into oligolamellar vesicles (OLV) and small unilamellar vesicles (SUV) by preparative differential ultracentrifugation (150,000 x g for 1 h). Unentrapped DXR was removed by gel exclusion chromatography. OLV and SUV liposomes differed in size (mean diameters, 247 +/- 113 nm and 61 +/- 16 nm, respectively) and number of lamellae (two for OLV, one for SUV). Drug entrapment per unit of lipid was three to 5-fold higher in OLV than in SUV. In both liposome populations more than 95% of the entrapped drug was membrane-associated. Physical studies on these two vesicle populations revealed higher motional restriction and greater susceptibility to iodide-mediated fluorescence collisional quenching of DXR in the small vesicles. OLV showed superior stability in the presence of plasma as determined by the fraction of DXR retained by the vesicles. It was also found that the tissue distribution of DXR in SUV follows a pattern different from that of DXR in OLV and resembling that of soluble DXR. In accordance with these differences in patterns of tissue distribution, animal studies demonstrated that DXR in OLV is significantly less toxic than DXR in SUV and more effective in a tumor model with predominant involvement of the liver. These results indicate that vesicle size and/or number of lamellae play an important role in optimizing liposome-mediated delivery of DXR, and that oligolamellar liposomes are distinctively superior to small unilamellar liposomes when fluid phase formulations (Tm less than 37 degrees C) with bilayer-associated DXR are considered. PMID- 2245213 TI - Partition of synaptic membranes in aqueous two-phase systems at subzero temperatures by using anti-freeze solvent. AB - The freezing point of aqueous two-phase (liquid-liquid) systems containing water, dextran and poly(ethylene glycol) has been lowered by including glycerol. Biological membranes, obtained by fragmentation of a crude synaptosomal preparation from calf brain cortex, have been included in the two-phase systems. The effects of temperature and the concentration of glycerol on the partition of the membranes within the systems have been investigated. Considerable stabilisation of the membranes was noticed when they were partitioned at -10 degrees C compared with 0 degrees C. The influences of glycerol, ethylene glycol, N,N-dimethylformamide and tetrahydrofuran on the phase-forming properties of the systems and on enzyme activities are also presented. Possible use of the above systems for studies and separation of biological membranes are discussed. PMID- 2245214 TI - [Physico-chemical characteristics of endogenous regulatory oligopeptides]. AB - Analysis of amino acid residue content in endogenous regulatory oligopeptides possessing a preset spectrum of functional activity has been made. It has been shown that compared to proteins the oligopeptides contain a greater number of positively charged and cyclic radicals. All 525 oligopeptides with the preset spectrum of functional activity contained in EROP-Moscow data bank were found to have the same physicochemical characteristics. PMID- 2245215 TI - [The effect of the charge of aromatic amino acid, peptide and protein molecules on the rate of radical formation during UV-irradiation]. AB - It has been shown that the rate of radical formation under UV-irradiation of some aromatic amino acids, peptides and proteins abruptly increases with pH rise in the region 9.5-11. This effect is observed only in the case when the total charge of the molecule after ionization remains negative. PMID- 2245216 TI - [The nature of luminescence quencher in UV-irradiated proteins]. PMID- 2245217 TI - [Modulation of the intensity of fluorescence of aqueous solutions of proteins by magnetic field]. AB - Effect of the constant magnetic field with up to 3.2 X 10(-4) A/m intensity on the fluorescence of papain aqueous solutions was investigated. It has been shown that depending on the magnetic field direction a reversible decrease or increase of fluorescence intensity takes place. The variation of fluorescence intensity under the influence of magnetic field is maximal under excitation at long wave ultra-violet light. The effect increases with the increase of temperature, increases linearly with the increase of magnetic field intensity but doesn't depend on protein concentration in diluted solutions. The examination of the data leads to the conclusion on the existence of two possible mechanisms: the variation of properties of surface tryptophan residues environment and paramagnetic orientation of protein globule under the influence of a magnetic field. PMID- 2245218 TI - [The effect of zinc ions on the structure and function of lactate dehydrogenase M4]. PMID- 2245219 TI - [Characteristics of distribution of amino acid residues in the primary structure of calmodulin]. AB - Systemic analysis of the peculiarities of distribution of di-, tri- and tetrapeptide residues in amino acid sequence of calmodulins of different origin has been carried out. A conclusion is made that all the examined repeated tri- and tetrapeptide residues with comparatively low conformation mobility enter the alpha-helical conformations with low mobility in beta-turns, and tri- and tetrapeptides with intermediate meaning of conformation entropy in beta-sheet conformations of the calmodulin molecule. PMID- 2245220 TI - [Selective effect of ionization of nitrogen bases on the thermostability of AT- and GC-pairs of DNA]. AB - The ionization specific influence of nitrogen bases on thermostability of AT- and GC-pairs of DNA has been investigated by the method of DNAs melting temperature analysis. It has been shown that the change of temperature interval of DNA helix coil transition when changing pH environment is due to specific ionization of AT- and GC-pairs of nitrogen bases. PMID- 2245221 TI - [Structural characteristics of DNA from sarcoma 45]. AB - It is shown that thermodynamical parameters of thermal melting and the content of 5-methylcytosine for tumor DNA of sarcoma 45 differ from DNA in the norm. The reason of such difference is the presence of regions with changed DNA structure in sarcoma 45, which occurs apparently owing to hypermethylation of cytosine in tumor DNA. PMID- 2245222 TI - [Calculation of the degree of superhelical DNA in model chromatin fibers]. AB - Effect of the length of DNA internucleosome regions (L) on writhing number (Wr) was analysed. It has been shown that Wr(L) is a periodic function. In any period Wr decreases, if L increases. The process of chromatin activation is proposed. The value sigma is shown to be equal to -0.086 for certainly inactive and -0.107 for potentially active and active chromatin models. PMID- 2245223 TI - [Possible role of intracellular electrical fields in the orientation of microtubule assembly]. PMID- 2245224 TI - [The causes for changes in optical properties of myofibril suspensions during relaxation]. AB - Increase in the asymmetry of light scattering diagram of myofibril suspensions resulting from their relaxation was shown to be not associated with essential alterations of the myofibrillar size. Optical changes caused by relaxation appear to be conditioned by the inner rearrangement of the myofibrillar structure. PMID- 2245225 TI - [Two phases in development of chemiluminescence during lipid peroxidation induced by Fe2+ ions]. AB - After cessation of the stirring of reagents in the egg yolk lipoprotein suspension where lipid peroxidation had been initiated by ferrous ions a drop of chemiluminescence (CL) was observed after a lag period, the duration of which increased in the course of stationary-state CL development. The CL intensity was but slightly dependent on oxygen pressure in the gas phase above incubation mixture within oxygen partial pressure limits 760-40 mm Hg. These data suggest that the CL quantum yield is growing during lipid peroxidation development as a result of the formation in the system of some compounds amplifying the CL intensity and/or development of a new CL reaction whose rate depends purely on oxygen and whose photon emitters are different. PMID- 2245226 TI - [Electrochemical potential difference for H+-ions as a regulator of redox profile of membrane during ATP-dependent ion transport in E. coli]. AB - The importance of delta mu H+ for transport of K+ via K(+)-ionophore and H(+) K(+)-pump was studied. It was shown that the operation of the pump was decelerated by oxidant ferrycyanide, whereas sulfhydryl reagent dithiothreitol (DTT) drastically accelerated ATP driven ion exchange. Introduction of protonophore CCCP into the medium completely blocked the pump operation. However, the addition of DTT after CCCP restored the high level activity of the pump. At the same time DTT was unable to restore K+ accumulation after CCCP in aerobically grown bacteria for which the K+ uptake was performed across the electrical field gradient. Thus it was established that delta mu H+ was necessary for ATP driven ionic systems as a regulator of the membrane redox state. PMID- 2245227 TI - [Correlation between the lymphocyte surface potential and membrane potential in various physiological states]. AB - Present work shows that changes in the surface potential (SP) are linearly connected with alterations of the cell membrane potential (MP) at three physiological states of the organism: control (C), induced cancerogenesis (IC) and total reaction of the organism to damage (TRD). In the control greater SP changes are corresponded with the least MP changes. When SP is changed almost by 100%, MP change is about 20%. In the course of TRD development a reverse relationship is observed: 20% change of the charge is corresponded by a practically 100% change of MP. The relationship indices of MP and SP change in the course of TRD and in the control are equal: with a decrease of MP the lymphocyte SP is also decreased. At the initial stages of IC development the relationship index of MP with SP is changed. In this case a 20% decrease of SP is accompanied by a 60% increase of MP. PMID- 2245228 TI - [Anisotropic electric conductivity of bacterial suspensions induced by external electric field]. AB - The anisotropy of electrical conductivity of suspensions of such bacteria, as E. coli, Serratia marcescens, Pseudomonas fluorescens induced by a sinusoidal external electric field and relaxation of the anisotropy after switching off the field were investigated. On the basis of the experimental relationships the anisotropy of electrical polarizability and coefficient of rotational diffusion of the cells were evaluated. The anisotropy of electrical polarizability and coefficient of the rotational diffusion obtained are in a good agreement with the available data of other methods. PMID- 2245229 TI - [The equation for platelet aggregation rate]. AB - A platelet aggregation model in shear flow taking into account the kinetics of intercellular fibrinogen bond formation limited by aggregated platelets rotation time was considered. For this consideration the average duration of platelets interaction in flow with shear rate value G is shown to be pi/4G. One fibrinogen bond is sufficient to form a solid aggregate between two platelets. The equation for single platelets disappearance rate concerned with intercellular fibrinogen bond formation, stochastic character of bond distribution in collided platelets and hydrodynamically controlled interaction time was obtained. The Hill's approximation for the obtained aggregation rate dependences was suggested and appropriate constants were determined. The qualitative criterion of platelets aggregating systems behavior was introduced. PMID- 2245230 TI - [Comparative analysis of the mechanism of metabolism of storage compounds in the cell clock]. AB - The effect of the autooscillation period Td of various kinetic mechanisms for D in equilibrium with S exchange (D storage form of the compound S) was theoretically studied in a system of the D in equilibrium with S in equilibrium with G1 type, where G = S in equilibrium with G1 is a relaxation autooscillator. The kinetics studied were linear, hyperbolic and cooperative. With a rapid D in equilibrium S exchange all the three kinetic mechanisms were shown to yield approximately equal values of Td. However, they greatly differ in energy losses for stray substrate recirculations in the D in equilibrium S cycle: the least losses were in the case of the cooperative kinetics and the greatest in that of the linear mechanism, while the hyperbolic mechanism yielded intermediate values. The results obtained hold for any energy-dependent mechanisms of D in equilibrium S synthesis and are independent of the specific pattern of the oscillator G. PMID- 2245231 TI - [The mechanism of water transport in the epidermis]. AB - Possible mechanisms of water transport through Stratum Corneum (SC) in the process of insensible perspiration are investigated. Electrometric methods developed for measuring water flow density through SC are used. Data showing the reverse osmotic mechanism of water transport through the SC selective membrane are obtained. It is shown that the water flow density through SC controlling the evaporation rate from the skin surface in the process of insensible perspiration depends upon the skin capillary pressure. PMID- 2245232 TI - [Possible distribution of electrons during galvanic exposure in the vicinity of the external surface of the body]. AB - Redistribution of potentials resulting from electron injection into the body volume was estimated for the set distribution of concentrations of Na+,K+,Cl- in the vicinity of the body outer surface obtained from Poisson equation and assumption concerning Bolzman distribution of these ions (generalization of Gui Chapman model). Relation of the potential minimum with the parameters of the system of distance from the outer surface was shown, i.e. with the maximal electron concentration, which can help while optimizing the galvanic effect. PMID- 2245233 TI - [Interaction of vanadate with the contractile system of striated muscles in the presence of natural analogs of ATP and ADP]. AB - Vanadate produced dissociation of rigor-activated (calcium-free) fibres or rabbit m. psoas muscle in the presence of the studied various natural analogs of ATP (NTP) at optimal concentrations. By the degree of sensitivity to vanadate it is possible to establish the order ATP approximately greater than CTP greater than UTP greater than ITP greater than GTP. This series corresponds to the order for actomyosin NTPases qualitatively. Addition of corresponding NDP to fibres produced a decrease of the rigor fibres tension. Vanadate in comparable concentrations does not change the mechanical properties of fibres in the presence of NDP. At high concentration (greater than 10 mM) vanadate produced relaxation of the rigor fibres even in the absence of nucleotides. This effect is irreversible. PMID- 2245234 TI - [The mechanism of calcium control of smooth muscle tonic contraction]. AB - It has been shown in the experiments carried out on a fraction of inverted vesicles of myometrium sarcolemma that ATP-dependent Ca2+ transport system prevents dissipation of the calcium gradient directed from the intervesicular space outward with subsequent establishment of the stationary level of cation content inside the membrane vesicles (a blocker of electro-controlled calcium channels diltiasems was present in the incubation medium). Ortovanadatean inhibitor of the sarcolemma calcium pump suppressed Ca2+ stationary exchange in the vesicles fraction. The value of calcium stationary content in the vesicle membrane was regulated both by a change of the calcium pump activity (by varying Mg2+ concentration in the ATP-containing incubation medium), and by modification of calcium permeability of the vesicles (by varying concentration of ionophore A 23187 in this medium). In the presence of diltiasem and ortovanadate the Ca2+ basal current entering the myocytes from hyperpotassium washing solution activated the smooth muscle tonic contraction. In the absence of ortovanadate no contractile response was observed. On the basis of the evidence obtained a mechanism of calcium control of myometrium tonic contraction is proposed. According to this mechanism the Ca2+ current entering the unexcited myocytes under physiological conditions is efficiently compensated by the calcium pump of the sarcolemma. The inhibition of the latter (or an increase of the sarcolemma basal calcium permeability) provides further slow transition of the stationary value of Ca2+ concentration in the myoplasm to a new higher level and activation of the smooth muscle contraction accordingly. PMID- 2245235 TI - [Muscle energy transfer during a given wave-like movement of human body segments]. AB - The paper deals with a movement of two voluntary segments fixed in a joint and connected by a muscle in a multi-segment biomechanical system of human body. The muscle model is a four-element mechanical system. The mechanical movement energy brought into the "segments-muscle" system from the segments preceding the next ones is studied. The movement in which the total multi-segment system of the human body participates is described by the wave equation. Conditions concerning applying active muscle efforts and correlating velocities of muscle ends movement which provide the maximal value of transferred energy have been found. It is shown that the use of "artificial muscles" type devices promotes activization of energy transfer processes between segments. PMID- 2245236 TI - [Interaction of the antineoplastic agent mitoxantrone with poly-G.poly-C]. PMID- 2245237 TI - [Structural changes in human IgG subclasses during heat aggregation]. PMID- 2245238 TI - [Oxygen activation by human peripheral blood T- and B-lymphocytes during adhesion to glass and exposure to specific mitogens]. PMID- 2245239 TI - [Energy transformation in mitochondria. Active role of the membrane]. PMID- 2245240 TI - The trial of Abner Baker, Jr., MD: monomania and McNaughtan rules in antebellum America. AB - On the third of October 1845, in a small mountain community in Kentucky, Abner Baker, Jr., MD, was executed for the murder of his brother-in-law Daniel Bates. At the trial Baker's attorney argued unsuccessfully that at the time of the crime the accused suffered from monomania, a form of mental disease, and therefore should not be held responsible for the act. The trial bears historical significance by the fact that it took place only a year after the formation of the Association of Medical Superintendents of American Institutions for the Insane, the first professional organization of psychiatrists in the United States, and two years after the McNaughtan ruling in British jurisprudence which molded the insanity plea around the concept of "knowing right from wrong." Because it took place at this particular juncture in the history of both law and medicine, it provides a revealing portrait of how medical and legal concepts on insanity interacted with the indigenous social and political circumstances of antebellum America. PMID- 2245241 TI - Who's afraid of forensic psychiatry? AB - Forensic psychiatry has come under mounting criticism from the press and other medical professionals, largely for its participation in the insanity defense. The author argues that the expertise available from the specialty is of increasing importance to psychiatry as a whole, as more and more legal issues become relevant to the practice of general psychiatry, and should be actively encouraged and legitimized rather than ostracized. All psychiatrists should be exposed to forensic principles and practices during their training, and the ability of forensic psychiatrists to serve as transducers between the clinical and the legal/judicial should be increasingly used to present the clinical viewpoint effectively in courts and legislatures. PMID- 2245242 TI - Axis I and Axis II diagnostic parameters of homicide. AB - A series of 100 murderers was examined to discern overall patterns of psychopathology. In addition, demographic and other discriminating factors were used to test the hypothesis that murderers do not constitute a homogenous population and that subgroups will differ diagnostically. DSM-III diagnostic criteria were used to make each diagnosis. The sample was found to be representative of the universe from which it was drawn at least as could be determined by available comparative criteria. Four Axis I (psychoses, substance abuse, dysthymia, no Axis I) and three Axis II (antisocial, borderline, no Axis II) diagnostic categories accounted for more than 80 percent of the study population. The murderers were found to be a heterogenous population, and subgroups based on a combination of assailant's crime pattern, sex, prior criminal history, and relationship to victim manifested different prevailing diagnostic patterns. PMID- 2245243 TI - Co-occurring mental disorders among criminal offenders. AB - Many convicted offenders suffer from major mental disorders. These offenders commit crimes with great frequency. They do not receive mental health care and are often found in isolation cells of correctional facilities. The present investigation examined lifetime multiple disorders, measured by the DIS, among a representative sample of male penitentiary inmates. Pure forms of the major mental disorders were rare. All possible combinations of the major disorders were found to exist. No patterns of groupings of disorders were evident. PMID- 2245244 TI - Posttraumatic stress disorder in tort actions: forensic minefield. AB - The authors discuss posttraumatic stress disorder (PTSD) as a basis for personal injury litigation. Three case examples raise issues related to: (1) the controversy surrounding expansion of tort liability, (2) the courtroom use of psychiatric nomenclature as represented in the DSM (e.g., PTSD), and (3) ethical concerns regarding psychiatric expert witnesses. Psychiatrists became easy targets when problems related to personal injury "stress" cases developed. A careful analysis, however, demonstrates that the issues are complex and multifaceted. For example, tort liability expansion was primarily instituted to compel a greater provision of liability insurance, not to reward stress claims. The increasing use of psychiatry's DSM in the courtroom has occurred despite explicit precautions against forensic application. Finally, the need for psychiatric expert witnesses has increased because courts have gradually usurped some psychiatric clinical prerogatives and because there has been a trend toward greater consideration of emotional pain and suffering. Although psychiatric expert witnesses have not been beyond reproach, critics have attempted to impeach the entire psychiatric profession for the questionable actions of the minority. The authors provide a detailed analysis of current problems, offer suggestions for improvement, and provide an educational counterpoint to the "hysterical invective" that often greets psychiatric testimony. PMID- 2245245 TI - Disposition of insanity acquittees in the United States Military. AB - Recent amendments to the United States Code of Military Justice have essentially adopted the federal mental nonresponsibility rule or insanity defense. The prior standard, as outlined in the American Law Institute's Model Penal Code, has been abandoned. Notably absent is a system to address the disposition of the military insanity acquittee. This raises concerns regarding recidivism and the military's role in mitigating potential dangerousness. Relevant civilian and military law is reviewed, two cases described, and possible remedies proposed. PMID- 2245246 TI - Prearraignment forensic evaluation: the odyssey moves east of the Pecos. AB - Although the ethical guidelines of both the American Psychiatric Association and the American Academy of Psychiatry and the Law explicitly prohibit the forensic examination of criminal defendants before appointment of counsel, except for the purpose of providing emergency medical care and treatment, the practice continues in many parts of the country. This article presents a recent case in which this practice was challenged on appeal, to serve as a focus for discussion of the evolution of, and rationales for and against, these ethical positions. It will also serve as a focus to examine the legal views concerning such examinations, derived from the appeal of the decision in the case itself as well as decisions in similar cases. PMID- 2245247 TI - Development of a new classificatory model of malingering. AB - Inclusion criteria for the classification of malingering are shaped and largely predetermined by our explanatory theories. Current theories have postulated the motivation to malinger is either the product of underlying psychopathology (pathogenic model) or criminal backgrounds (DSM III-R model). I have proposed a third model that malingering is typically an adaptive response to adverse circumstances which may best be understood in the context of decision theory. Based on this approach I have argued that indices of malingering should be empirically derived and focused on clinical presentation. Finally, I have proposed a preliminary model for the classification of malingerers which combines clinical data with corroborative evidence. PMID- 2245248 TI - The Society for the Study of Addiction 1884-1899. PMID- 2245249 TI - Red cell deformability and haematological disorders. AB - Blood rheology is the science of the flow and deformation of blood. Clinically, blood rheology is important because circulatory resistance has two major components, vascular and rheological. In large vessels, blood rheology should be considered in terms of bulk flow, the viscosity of blood depending mainly on red cell concentration and plasma viscosity and, to a lesser extent, on red cell deformability and aggregation. In the microcirculation, where cells must deform to pass through narrow capillaries, cellular rheology (i.e. the deformability of individual cells) is a major determinant of resistance to flow. This ability to deform is also a determinant of the cell's survival time in the circulation. The deformability of the red cell is essentially linked to its structure (i.e. its cellular geometry, membrane properties and cytoplasmic viscosity); thus structural abnormalities, as found in some haematological disorders, can be expected to affect blood flow in the microcirculation and/or red cell lifespan. Blood rheology is a relatively new discipline as applied to the practice of haematology. In 1985 the International Committee for Standardization in Haematology (ICSH) established an Expert Panel on Blood Rheology which has subsequently issued guidelines on the measurement of blood viscosity and erythrocyte deformability and on tests such as erythrocyte sedimentation rate and plasma viscosity that are used to monitor the acute phase response in inflammatory disease. Rheological methods now have sufficiently good sensitivity and specificity for their application to a wide variety of clinical disorders. This review illustrates their potential application to haematological disorders that cause abnormal deformability of red cells. PMID- 2245250 TI - A logical approach to the investigation of red cell enzymopathies. AB - This relatively rare group of disorders may cause quite marked morbidity and occasionally be life-threatening. As their inheritance is largely known accurate information in one family member has obvious benefits to other family members as well as the patient. The identification of the defect is dependent on an accurate clinical story which can be used to guide both the use and the interpretation of the various laboratory tests available. From the clinical aspect the enzymopathies can be divided into various broad groups. First, those involving the main glycolysis which produces the red cell's energy requirements in the form of ATP. Defects of this pathway generally cause a non-spherocytic haemolytic anaemia. Second, those involving the pentose phosphate shunt which maintains the redox potential of the cell necessary for its protection against oxidant stress. The commonest enzyme deficiency world wide, G6PD, is in this pathway and is characterized by stress-induced haemolytic crises. Third, defects of the various linked reactions. The most important of these are the methaemoglobin reductases which catalyse the reduction of methaemoglobin to functional haemoglobin and the enzymes in the Rapoport-Luebering shunt which can modulate the 2,3-DPG level. Whilst defects of these metabolic pathways make up the majority of cases associated with haemolysis, defects of other enzymes, on the whole less critical to the red cell's survival, must occasionally be considered. The red cell, because of its relatively easy availability, can be used as a 'biopsy tool' in the diagnosis of some systemic disorders in which the red cell enzymopathy is not the main feature of the disease. Such considerations are particularly important owing to the technological advances that have occurred in the last 10-15 years which have enabled correct assignment of an increased number of difficult cases. Not only is it possible to characterise the variant enzymes more accurately but it is now possible to have a 'metabolic window' on the red cell and examine it for the derangements of metabolism that characterise the various enzyme deficiencies. PMID- 2245251 TI - Human immunodeficiency virus type 2 (HIV2). AB - In the mid 1980's a second human retrovirus, capable of causing the acquired immunodeficiency syndrome (AIDS), was isolated from patients of West African origin. This virus, now called human immunodeficiency virus type 2 (HIV2), was found to be distinct from human immunodeficiency virus type 1 (HIV1) but closely related to simian immunodeficiency viruses (SIV). Although the genomes of HIV1 and HIV2 are similar there are significant differences in nucleotide and amino acid sequences, most marked with the envelope genes and proteins. Both viruses, however, bind to the same CD4 cellular receptor. HIV2 is largely confined to West Africa where it is the dominant HIV, though patients infected with HIV2 have been described in Europe and America. Its transmission, clinical features and immunological effects are similar to those associated with HIV1 infection. However, there is some suggestion that the incubation period from infection to clinical disease may be longer than with HIV1 and that HIV2 may be less pathogenic. Patients with sera that react with both HIV1 and HIV2 antigens have been described, but it is unclear whether this represents serological cross reactivity or true double virus infection. Testing for HIV2 antibodies may become increasingly necessary in HIV2 non-endemic areas. PMID- 2245252 TI - Immunoregulatory cell dysfunction in chronic B-cell leukemias. AB - Chronic B-cell malignancies are routinely characterized as B-cell clonal diseases that have signs and symptoms primarily related to the continuing expansion of these cells. This review discusses chronic lymphocytic leukemia, multiple myeloma and hairy cell leukemia from the perspective of secondary abnormalities in non malignant cells. Thus, our main purpose is to elaborate on the alterations/abnormalities of the immunoregulatory (IR) cells in these diseases and focus on the qualitative and quantitative aspects of T-cells, natural killer (NK) cells and monocytes. The relevance of the IR-cell changes to the basic disease process and their complications are emphasized. PMID- 2245253 TI - The current status of interferon alpha in haemic malignancy. AB - Interferon-alpha (IFN alpha) has been extensively studied, both in clinical trials and in the laboratory. The cytokine has proved most effective in haemic malignancy, in particular hairy cell and chronic granulocytic leukaemia. This article deals with the current status of IFN alpha in these conditions and the possible basis of this sensitivity. Other less responsive haemic malignancies are also discussed. PMID- 2245254 TI - The management of early Hodgkin's disease. AB - Hodgkin's disease has provided a focus of academic attention for haematologists, radiotherapists and oncologists over the last 20 years but nevertheless there is considerable controversy over the management especially of early presentations. Options include performing a staging laparotomy and splenectomy with radiotherapy for pathological stage I and II disease, clinical staging with combined chemotherapy and radiotherapy, clinical staging with either extensive radiotherapy or with limited radiotherapy and close surveillance, or finally, clinical staging and treatment with chemotherapy alone. An appropriate management decision depends upon an assessment of the disease and also on the impact of treatment side-effects on the individual patient. PMID- 2245255 TI - Effects of chemotherapy on fertility. AB - Over recent years radical improvements in the treatment of malignant disease have resulted in the cure of patients in or approaching reproductive age, and with that cure, the effects on gonadal function have become apparent. Gonadal failure is particularly important in Hodgkin's disease, germ cell tumours, choriocarcinoma, and leukaemia, diseases of young people which are largely curable. Premature ovarian and testicular failure are easily missed by doctors concerned primarily with the erradication or arrest of a life-threatening disease, but for the patient the hormonal, psychological and social sequelae of treatment may be devastating. In this article we review the effects of chemotherapy on gonadal function and discuss the management of gonadal failure. PMID- 2245256 TI - Graft-versus-host disease--a histological perspective. PMID- 2245257 TI - MHC restricted and non-restricted killer lymphocytes. AB - Cytotoxic lymphocytes are either MHC-restricted (cytotoxic T-cells) or nonrestricted (natural killer NK-cells), although cells of the monocyte/macrophage lineage are also cytotoxic, and lymphocytes or phagocytic cells expressing Fc-receptors for immunoglobulin can function as antibody dependent killer cells (referred to as antibody-dependent cellular cytotoxicity: ADCC). Antigen-specific T-lymphocytes recognise their target antigen in the context of MHC class I components, focusing their attack only against those cells expressing the relevant antigen specificity on their cell surface. A more primitive and alternative mechanism exists whereby NK-cells, classified as large granular lymphocytes (LGL), are able to kill in a non-specific manner, not requiring prior sensitisation to antigen. Both antigen-specific T-cells and LGL mediate their cytotoxicity through the release of cytotoxic molecules at the target-effector cell interface. LGL also have a regulatory role in the immune system through the release of cytokines, and can be distinguished from T lymphocytes by the expression of distinct phenotypic markers (CD16+, CD56+) and they lack CD3 antigen expression or rearranged alpha/beta or gamma/delta T-cell receptor gene products. Cytotoxic activity is positively regulated by interleukin 2 (IL-2) and interferon (IFN), whilst prostaglandins and transforming growth factor-beta (TGF beta) diminish activation and effector pathways. Cytotoxicity mediated by NK- and T-cell populations are principally involved in the defence against microbial infections and neoplasia; the abrogation of cytotoxicity either by direct interaction of 'suppressor factors' with effector cells, or indirectly by reducing cytokine production can inevitably lead to the proliferation of the disease. PMID- 2245258 TI - Morbid jealousy: a review and cognitive-behavioural formulation. PMID- 2245259 TI - Stress and puerperal psychosis. AB - Eighty-eight in-patients admitted to a psychiatric mother-and-baby unit and 80 randomly selected recently delivered women in the general population were interviewed using the LEDS. Only five of 33 patients (15%) with puerperal psychosis had provoking agents, which is less than the figure for women in the community (36%). Provoking agents were present in only 8 of 25 patients with post natal depression, but they were present in seven of nine patients with pre-natal depression and eight of nine women in the community with pre-natal depression. PMID- 2245260 TI - Is psychiatric training still improving? AB - A postal questionnaire inquiring about postgraduate training was directed to all consultants appointed to a post in general psychiatry for the first time between 1 October 1985 and 30 September 1986. Compared with previous surveys there is, overall, more expressed satisfaction with training in psychogeriatrics, supervised ward consultations, individual psychotherapy, work in the community, and with medico-legal experience. Diminished satisfaction is expressed in training in child and adolescent psychiatry, epidemiology, psychology, and neurology. An improved system of monitoring by the Royal College of Psychiatrists and the Joint Committee for Higher Psychiatric Training is suggested in order to further improve training. PMID- 2245261 TI - Psychiatric diagnoses as predictors of suicide. A comparison of diagnoses at conscription and in psychiatric care in a cohort of 50,465 young men. AB - In a cohort of 50,465 Swedish men conscripted for military service in 1969-70, the relative risk for suicide was 3.1 (95% Cl 2.3-4.0) among those who had a psychiatric diagnosis at conscription, and 16.7 (95% Cl 13.8-20.1) among those who had a psychiatric diagnosis in in-patient care during a 13-year follow-up. Of the diagnoses at conscription, only neurotic disorder, personality disorder and drug dependence were associated with a significantly increased risk for future suicide. Among those who were admitted to hospital, almost all in-patient diagnoses were associated with a significantly increased suicide risk. Although a psychiatric diagnosis in in-patient care was a strong predictor of suicide, only 44% of all 247 men who committed suicide had ever been treated in in-patient psychiatric care. PMID- 2245262 TI - Schizophrenia and crime. A longitudinal follow-up of 644 schizophrenics in Stockholm. AB - To compare the crime rate of schizophrenics with that of the general population, data from the Central Swedish Police Register on 790 schizophrenic patients discharged from hospitals in Stockholm in 1971 was analysed for the period of 1972-86. Relative risk of criminal offence was assessed by comparing the observed number of offences committed with the expected number (estimated from official statistics). The crime rate among male schizophrenics was almost the same as that in the general male population, whereas among females it was twice that of the general female population. The rate of violent offences was, however, four times higher among the schizophrenics. The violence recorded was almost exclusively of minor severity. PMID- 2245263 TI - Langfeldt's schizophreniform psychoses fifty years later. AB - As a result of follow-up studies published in 1937 and 1939, Langfeldt divided schizophrenia into two groups; 'typical schizophrenia' which had a poor outcome, and the 'schizophreniform psychoses' which had a less typical clinical picture of schizophrenia and a good outcome. Langfeldt's cases of schizophreniform psychoses were reclassified according to the ICD-9 and DSM-III-R diagnostic systems. Most of the schizophreniform psychoses did not appear 'schizophrenia-like' at all, but turned out to be mainly affective disorders. Those included in Langfeldt's diagnosis of 'schizophreniform psychoses' were found to be too heterogenous to validate the existence of this syndrome. PMID- 2245264 TI - Impaired ability of schizophrenics, relative to manics or depressives, to appreciate social knowledge about their culture. AB - Twenty schizophrenics, 20 manics, and 20 depressives were given two sets of multiple choice questions, one testing the subject's social knowledge of how people tend to act in a social situation and the other tapping their knowledge of events or objects which are relatively free of a social component. Schizophrenics were significantly impaired on the former set of questions relative to manic, and were significantly worse on both than depressives. It is suggested that these results represent an objective measure of the social naivete of schizophrenics. The significant difference from manics indicates that the results are not merely the general effects of psychosis, particularly because the manics performed worse on an attentional test than the schizophrenics. PMID- 2245265 TI - Regional cerebral blood flow in patients with affective disorders. AB - Regional cerebral blood flow at rest was measured in 38 patients with major depressive disorders and 16 controls by SPECT with inhalation of xenon-133. All subjects had been withdrawn from medication. The mean hemispheric cerebral blood flow was not statistically different between the controls and the different subgroups of depressed patients defined either by biological markers or clinical characteristics. However, the predominantly cortical blood flow, measured on the outer cerebral rim of the third tomographic slice, was significantly lower on the left hemisphere in bipolar patients when compared with normals and unipolar patients. The same lateralisation was observed in patients with an endogenous depression according to the Newcastle scale. PMID- 2245266 TI - Dichotic perception and memory following electroconvulsive treatment for depression. AB - Verbal and visuospatial memory and dichotic listening performance were examined in 15 acutely depressed patients with no history of ECT, 17 depressed patients currently in remission, 15 remitted depressed patients who had received ECT six months or more in the past, and 20 normal controls. The neuropsychological functioning of an additional group of 10 acutely depressed patients was also studied before and two weeks after ECT. The results revealed some evidence of logical and autobiographical memory impairment two weeks following ECT, but no evidence that ECT impaired dichotic listening ability. Rather, a normalisation of hemispheric laterality was apparent on the dichotic listening task following ECT and the concomitant relief from depression. There was also no evidence of cognitive dysfunction on any task in individuals who were tested six months or more following their last ECT treatment. PMID- 2245267 TI - Towards a cognitive-behavioural intervention for adult grief reactions. AB - Published accounts of behavioural interventions for grief have relied on exposure and habituation to grief cues as the primary strategy. Such an approach is excessively narrow, since it does not adequately confront the challenges that are posed by a bereavement. Many people cope with a bereavement by themselves, and for those, intervention may well be counterproductive. A cognitive-behavioural intervention, following models for depression/anxiety, can assist vulnerable individuals obtain a more rapid or complete adjustment. PMID- 2245268 TI - The value of the Claybury Selection Battery in predicting benefit from group psychotherapy. AB - Before receiving psychodynamic group psychotherapy at the Uffculme Clinic four groups of out-patients were assessed on the Claybury Selection Battery and the SCL 90, and therapists were asked to predict their progress. Outcome was assessed at about three months and one year by patients' self-reports of symptom change on the SCL 90 and therapists' ratings of progress. Only one of the three Claybury questionnaires, the TEQ, which measures attitudes to treatment, was significantly correlated with outcome, along with therapists' predictions. This result is different to that of a previous study which also found that outcome correlated with direction of interest (DIQ) and conservatism (C). The C and DIQ scales may provide useful predictive information only in a small proportion of cases. PMID- 2245269 TI - Two-year follow-up of the Sheffield Psychotherapy Project. AB - Of 40 depressed and anxious patients who received treatment during the Sheffield Psychotherapy Project, 31 completed the BDI and SCL-90 at two-year follow-up. At both group and individual levels, outcomes were very similar to those obtained at the completion of treatment. Substantial minorities of patients reported major life events and seeking further help for psychological problems during the two years, but these reports were not reliably associated with symptoms at follow-up. Patients recalled very different elements in prescriptive and exploratory therapies as helpful, with a notable emphasis upon prescriptive therapy's relaxation and anxiety management as a source of problem solution. PMID- 2245270 TI - A systematic inquiry into recollections of childhood experience and their relationship to adult defence mechanisms. AB - The relationships between childhood experience, measured by the PBI, and adult defence mechanisms, evaluated through the DMI, were examined in 114 subjects. There were modest but significant correlations between the primitive defences of 'turning against others' and 'projection' on the one hand, and a lack of parental care, as experienced by the subjects, on the other. 'Principalisation' (e.g. intellectualisation, isolation and rationalisation) and 'reversal' (e.g. negation, reaction formation, denial and repression) were positively associated with parental care. These findings account for only a small portion of the variance but show that, as with certain personality traits, actual or perceived childhood experience contributes in a recognisable fashion to the patterns of adult defences and behaviour. PMID- 2245271 TI - Incest, incestuous fantasy & indecency. A clinical catchment area study of normal weight bulimic women. AB - This systematic study of 112 consecutive referrals of normal-weight bulimic women from a circumscribed urban catchment area found that eight patients (7%) reported sexual abuse involving physical contact. Four (3.6%) of these described incest, but only in two cases (1.8%) did the incest occur in childhood. Just over 5% of the sample reported unlawful sexual intercourse in childhood or gross indecency. Eighteen additional patients reported incestuous fantasies and two of these were partly acted out. The study indicates that incest and sexual abuse reported by bulimics is usually in those multi-impulsive patients who also abuse alcohol or drugs as well as food. The reported prevalences of incest and indecency in normal weight bulimic women are only slightly higher than figures derived from general population surveys. PMID- 2245272 TI - Hypochondriasis and somatosensory amplification. AB - A self-report questionnaire completed by 177 out-patients showed that hypochondriasis and amplification had a zero-order correlation of 0.56, and in stepwise multiple regression amplification accounted for 31% of the variance in hypochondriasis, after sociodemographic variables had been accounted for. Fears of ageing and death, and a childhood history of illness in the family, increased the R2 to 0.50. Amplification was more powerful in women than in men and was also a significant (although weaker) correlate of somatisation, explaining 12% of the variance. Somatisation also correlated with being female, the propensity to seek medical care, and a diminished sense of efficacy over one's health. Our findings are consistent with the possibility that somatosensory amplification occurs in hypochondriasis. PMID- 2245273 TI - Are British psychiatrists racist? AB - Out of a sample of 220 British psychiatrists, 139 completed a questionnaire regarding a case vignette of psychotic illness. The sex and 'race' of the vignette were varied and the responses compared. The Afro-Caribbean case was regarded as that of an illness of shorter duration, and requiring less neuroleptics than the white case. Respondents judged the Afro-Caribbean case as potentially more violent and thought criminal proceedings were more appropriate. The female vignette was perceived as less violent, less criminal, and less likely to need neuroleptics. Cannabis psychosis and acute reactive psychosis tended to be diagnosed more often and schizophrenia less often in Afro-Caribbean cases, refuting the claim that psychiatrists tend to overdiagnose schizophrenia in this group. Such 'race thinking' (a form of stereotyping which is distinct from ideological racism) could lead to inappropriate management. PMID- 2245274 TI - A comparative study of psychiatric services in Japan and England. AB - Psychiatric services in Japan and England are compared using government statistics. In Japan, the number of in-patients per 100,000 population has increased from the 1950s, while that of England has decreased since 1954. Since 1972 the prevalence of in-patients has been higher in Japan than in England. The admission rate is lower in Japan than in England, and there are more long-stay patients. Most Japanese in-patients are admitted compulsorily, whereas most are admitted voluntarily in England. The attendance at out-patient clinics is higher in Japan than in England, but there are far fewer day-hospital places in Japan. Differing government policies are the main reason for these differences. PMID- 2245275 TI - Mass sociogenic illness by proxy: parentally reported epidemic in an elementary school. AB - "In a cluster of illness reported among students at an elementary school parents mentioned many signs and symptoms including headache, pallor, dark circles under the eyes, nausea, and vomiting--which they attributed to exposure to recurrent leaks of natural gas at the school. It is likely that the parents spread among themselves the notion of toxic exposure at the school. A questionnaire revealed no spatial clustering, but increased reports of symptoms were related to intense media coverage. A thorough environmental and epidemiological investigation was negative, there being no evidence of a continuing gas leak or other potential causes. At a strictly biological level, the complaints in this reported 'cluster' apparently represented the sporadic occurrence of common childhood illnesses. The possibility of an epidemic from toxic exposure at the school caused intense parental concern and led to a major public health problem. The established term 'mass sociogenic illness' seems inapplicable here because complaints did not come principally from the students and the apparent epidemic illness was not transmitted among them. The term 'mass sociogenic illness by proxy' is proposed to describe this incident, in which transmission in one group (the parents) resulted in reports of an epidemic in another group (students)." PMID- 2245276 TI - The depressed elderly living in the community. A follow-up study. AB - In a 1982 community survey, 23 elderly respondents were rated as having a depressive disorder by CATEGO. Twenty survivors were followed up three and a half years later. The depression had remitted within one year in seven cases but nine were still depressed. There is a need for ongoing education of GPs about the recognition and course of depression in the elderly. PMID- 2245277 TI - Post-partum psychosis in the Assir Region of Saudi Arabia. AB - The medical notes of 91 women who had a psychiatric illness requiring admission within nine months of childbirth were studied. The incidence of post-partum psychosis was 3 per 1000 births, of which 66% were affective psychoses. PMID- 2245278 TI - Panic attacks in chronic schizophrenia. AB - Of 20 patients attending a clinic for maintenance therapy of schizophrenia, seven had regular panic attacks, and these were often associated with agoraphobia and social phobia. Similar fears and avoidance in other cases were associated with paranoid ideas and negative symptoms. The relationship of panic to psychotic symptoms varied greatly. In two patients neuroleptics were associated with an increase in panic attacks. PMID- 2245279 TI - Schizophrenia and Marfan syndrome. AB - Five index patients and three of their first-degree relatives were affected both by schizophrenia and Marfan syndrome. Since the association appears statistically significant, the possibility of linkage disequilibrium between adjacent genes or a cytogenetic abnormality causing both disorders is suggested. These hypotheses are testable and hold promise in attempting to map the 'schizophrenia susceptibility gene' by the candidate-gene approach. PMID- 2245280 TI - Kluver-Bucy syndrome and psychiatric illness. AB - A 52-year-old woman, whose initial psychiatric presentation at the age of 15 was with a disorder resembling schizophrenia, developed symptoms of Kluver-Bucy syndrome, and is now thought to suffer from an organic psychotic disorder. Kluver Bucy syndrome must be distinguished from symptoms of schizophrenia or affective disorder; its presence suggests an organic process. PMID- 2245281 TI - Mood disorder, 'pre-ictal' psychosis and temporal lobe damage. PMID- 2245282 TI - Chronic fatigue syndrome. PMID- 2245283 TI - Racism, diagnosis and treatment. PMID- 2245284 TI - Unmet needs for medical care. PMID- 2245285 TI - Compliance with antidepressant medication. PMID- 2245286 TI - Insight. PMID- 2245287 TI - Skeleton services. PMID- 2245288 TI - 'Vital exhaustion' and myocardial infarction. PMID- 2245289 TI - 'Slowly progressive schizophrenia'. PMID- 2245290 TI - Temporal lobe atrophy versus open operculum in Asperger's syndrome. PMID- 2245291 TI - Bipolar affective disorder and anoxic brain damage. PMID- 2245292 TI - The prescribing debate (continued) PMID- 2245293 TI - The treatment of alcoholism by strychnine. PMID- 2245294 TI - Neuropsychology. PMID- 2245295 TI - Hereditary cerebral haemorrhage with amyloidosis--Dutch type. Magnetic resonance imaging findings in 7 cases. AB - The clinical history and magnetic resonance imaging (MRI) findings are presented of 7 patients with hereditary cerebral haemorrhage with amyloidosis--Dutch type (HCHWA-D). The diagnosis was based on clinical and genealogical data, was confirmed in 3 patients at autopsy and in 2 others by biopsy. Focal neurological signs, and at least some degree of global cognitive deterioration, were observed in all patients, with unequivocal dementia in 4. MRI showed haemorrhages and areas of gliosis and, to a variable extent, hyperintensity of the white matter in T2-weighted images. Neuropathological examination revealed a large recent haemorrhage together with residual lesions from previous haemorrhages or infarcts in all patients examined. The white matter lesions, present on MRI, turned out to be areas of 'incomplete infarction' with demyelination. It is concluded that (hereditary) amyloid angiopathy can lead to strokes, but also to subcortical ischaemic encephalopathy. Amyloid angiopathy should therefore be considered in the differential diagnosis of white matter lesions, found on CT or MRI, especially when patients present with a cerebral haemorrhage. The relationship between HCHWA-D and Alzheimer's disease, another disease with cerebral amyloid deposition and diffuse white matter involvement, is discussed. PMID- 2245296 TI - A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications. AB - Cerebrospinal fluid and serum immunoglobulin G from 1007 patients with suspected neurological disease were analysed by 2 methods: isoelectric focusing for the detection of oligoclonal banding, and quantitative measurement of IgG and albumin for the formulation of a Log IgG-Index. A comparison of the 2 methods in the detection of local synthesis of IgG showed that isoelectric focusing not only gave a much higher yield overall, with 282 patients showing local synthesis versus 225 for the Log IgG-Index, but also a higher specificity, with a false positive rate of 0% versus 3.5%. In addition, of the 282 patients positive by isoelectric focusing only 163 (58%) were positive by the Log IgG-Index. Of the 1007 patients studied, 206 had multiple sclerosis (MS), and isoelectric focusing showed local synthesis in 95% of clinically definite cases, with a 90% detection rate overall. The Log IgG-Index was positive in only 67% of clinically definite cases, with an overall 59% detection rate. Thus with the exceptions noted above, local synthesis of IgG as defined by isoelectric focusing is confined to demyelinating, inflammatory, infectious and postinfectious disorders. Our results compare very favourably with the published sensitivities of magnetic resonance imaging in the detection of abnormalities in multiple sclerosis, and better than those for evoked potentials. Where both these investigations are readily available isoelectric focusing provides a useful adjunct. For the majority of physicians and neurologists who do not have ready access to magnetic resonance imaging, isoelectric focusing is an excellent alternative. We would also recommend that it become the standard for the measurement of IgG abnormalities in the cerebrospinal fluid and that the use of quantitative data be abandoned for routine purposes. PMID- 2245297 TI - Congenital myasthenia associated with facial malformations in Iraqi and Iranian Jews. A new genetic syndrome. AB - Fourteen Jewish patients from 10 families of either Iraqi or Iranian origin with congenital myasthenia had associated facial malformations which included an elongated face, mandibular prognathism with class III malocclusion and a high arched palate. Other common features were muscle weakness restricted predominantly to ptosis, weakness of facial and masticatory muscles, and fatigable speech; mild and nonprogressive course; response to cholinesterase inhibitors; absence of antibodies to acetylcholine receptor; decremental response on repetitive stimulation at 3 Hz but no repetitive compound muscle action potential in response to a single nerve stimulus. This newly recognized form of congenital myasthenia with distinctive ethnic clustering and associated facial malformations is transmitted as an autosomal recessive disorder. The facial abnormalities may be secondary to the neuromuscular defect or may be primary and unrelated. Further studies are needed to elucidate the defect in neuromuscular transmission responsible for the pathogenesis of this syndrome. PMID- 2245298 TI - Myelopathy associated with human T cell lymphotropic virus type I (HTLV-I) in natal, South Africa. A clinical and investigative study in 24 patients. AB - Unexplained spastic myelopathy in black (Zulu) patients, similar to that seen in the tropics, has previously been described from Natal, South Africa. Following reports linking the human T cell lymphotropic virus type I (HTLV-I) to spastic myelopathy, we undertook a prospective and retrospective search for HTLV-I antibodies in 36 patients who were labelled as having unexplained myelopathy; 24 (66%) were positive and HTLV-I was isolated from 4 out of the 6 patients whose peripheral blood lymphocytes were cultured. Eighteen (75%) gave a short history (less than 6 months). There was a female preponderance (71%), spinothalamic dysfunction was common (55%) and as many as half were severely disabled (50% wheelchair bound). Routine laboratory studies showed no specific trends apart from hypergammaglobulinaemia and CSF pleocytosis (greater than 5 cells/microliter in 66% of patients). The total CSF protein was raised (greater than 0.4 g/l) in 45% of patients. The IgG index was greater than 0.7 in 15 of 19 patients. Conventional myelography did not show any specific abnormalities. Computer assisted myelography was undertaken in 22 patients; 3 showed arachnoiditis and 2 spinal cord atrophy. Periventricular lucencies were seen in 1 of 10 patients who had computed tomography of the head. Nerve conduction studies demonstrated abnormalities in 46% of the patients indicating that subclinical peripheral nerve dysfunction was common. Visual evoked responses were abnormal in only 1 patient but brainstem auditory evoked response studies showed some abnormality in 42% of the patients. The finding of HTLV-I antibodies in a significant number, and the isolation of HTLV-I from the blood in 6 of our black patients with noncompressive myelopathy, represents a substantial clinical advance. Future studies should define more clearly the role of the virus in this disorder. PMID- 2245299 TI - Heterogeneity in progressive aphasia due to focal cortical atrophy. A clinical and PET study. AB - Six patients with a slowly progressive aphasic disorder due to degenerative cortical disease are reported. The length of history varied from 18 months to 6 years. In 5 patients, there was a naming deficit, associated in 4 of these with some abnormalities in comprehension. One patient had a progressive history of reduced speech output, which was associated with an orofacial dyspraxia. All patients were studied neuropsychologically, and in addition regional cerebral metabolism was measured using position emission tomography. A localized left hemisphere deficit was found in all patients except 1, who had the longest history and the most profound clinical deficit, and who also had right hemisphere hypometabolism. The major brunt of the deficit was in the anterior portion of the left temporal lobe in all but 1 case, the patient with poor speech output who had a more severe left posterior frontal deficit. These findings suggest that in progressive aphasia due to focal cortical atrophy there is heterogeneity in the clinical presentation and anatomical site of the deficit, with possible implications for the underlying aetiology. PMID- 2245300 TI - Developmental dysmnesia in a poor reader. AB - A 22-yr-old subject with moderate developmental dyslexia experienced poor memory from an early age. In spite of normal intelligence he had great difficulty in learning historical and geographical names, mathematical formulae, poems and songs, and verbal series such as the letters of the alphabet and the months of the year. His recognition of familiar faces was also faulty at times. A battery of memory tests confirmed a moderate deficit of verbal as well as visual memory, whereas spatial memory was preserved. Other cognitive functions were intact, except for a mild reading disability. No evidence of brain pathology was provided by his history, neurological examination and CT scanning. PMID- 2245301 TI - Familial paroxysmal kinesigenic ataxia and continuous myokymia. AB - A large family with paroxysmal ataxia and continuous myokymic discharges is described. The disorder is of autosomal dominant inheritance. During attacks coordination of movements and balance are disturbed; often a postural tremor of the head and the hands and fine twitching in some of the facial and hand muscles are present. The attacks usually last a few minutes and may occur several times per day. They first appear in childhood and tend to abate after early adulthood. The attacks are frequently precipitated by kinesigenic stimuli similar to those in paroxysmal kinesigenic choreoathetosis. Their occurrence can be reduced or prevented by carbonic anhydrase inhibitors. Between attacks a slight postural tremor and ataxia was found in a few of the elderly affected members. Fine rippling myokymia was obvious in a few and could be detected on close inspection in about half of the adults. Electromyography (EMG) showed myokymic discharges in all affected members. The characteristics and reactivity of this myokymic activity suggest multiple impulse generation in the peripheral nerves. PMID- 2245302 TI - The comportmental learning disabilities of early frontal lobe damage. AB - Two adult patients are described who suffered bilateral prefrontal damage early in life and who subsequently came to psychiatric attention because of severely aberrant behaviour. A battery of developmental psychology paradigms (not previously used to assess neurologically impaired individuals) showed that social and moral development of these 2 patients was arrested at an immature stage. In comparison with other types of brain damage which disrupt cognitive development, frontal damage acquired early in life appears to provide the neurological substrate for a special type of learning disability in the realms of insight, foresight, social judgement, empathy, and complex reasoning. PMID- 2245303 TI - Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography. AB - We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset. PMID- 2245304 TI - Vestibular function in periodic alternating nystagmus. AB - The vestibulo-ocular reflex of 4 patients with periodic alternating nystagmus (PAN) was studied in detail. Rotational testing was used to investigate the horizontal semicircular canal-ocular reflex, canal-otolith interaction, and the dynamic otolith-ocular reflex. Results indicated abnormal gain and phase of the horizontal semicircular canal-ocular reflex during sinusoidal rotation and a variable rate of decay of postrotatory responses. Each patient had abnormal canal otolith interaction. An enlarged modulation component of the dynamic otolith ocular response was observed in each patient. This study supports the idea that PAN is caused by an instability in the velocity storage element, a hypothetical neural circuit that perseverates the eye movement response to both vestibular and optokinetic stimulation. Further, we postulate that PAN may be caused by lesions of the cerebellar uvula and nodulus or their connections with the brainstem vestibular nuclei. PMID- 2245305 TI - The anatomical basis of the caecocentral scotoma. New observations and a review. AB - It is shown that the 'papillomacular bundle' of optic nerve fibres, although a concept discussed frequently in the clinical literature, lacks a clear anatomical definition. It is suggested that the explanation for this is that the 'bundle' was originally described in autopsy studies of toxic amblyopia, not normal anatomy. The optic nerve fibre projection and vascular architecture of the caecocentral region of the retina is described. These anatomical features are discussed in relation to a number of possible anatomical explanations for the fact that a caecocentral scotoma is the characteristic field defect found in toxic amblyopia. We have been unable to identify a distinct anatomical feature which might explain this vulnerability but suggest that the problem has not as yet been clearly addressed by anatomists. PMID- 2245306 TI - The distribution of muscle weakness in upper motoneuron lesions affecting the lower limb. AB - To determine the distribution of weakness in the lower limb after upper motoneuron lesions the strength of 8 muscle groups was measured. Four groups of patients were studied: 22 control subjects, 16 patients with unilateral leg paresis, 4 patients with severe unilateral paralysis and 5 patients with paraparesis. In the testing posture (seated), patients with cerebral upper motoneuron lesions showed no selective loss of power in flexors or extensors on the contralateral side. Gravitational torques were included in the measurements. However, proximal muscles (acting at hip and knee) were significantly less severely affected than more distal muscles (acting at ankle and hallux). At any particular joint, physiological flexors and extensors were affected equally in both the hemiparetic and paraparetic subjects. As in the upper limb (Colebatch and Gandevia, 1989), the strength of muscles on the clinically unaffected side was reduced compared with control subjects, although no muscle groups were especially affected. PMID- 2245307 TI - Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. AB - From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected. PMID- 2245308 TI - Volume conduction of the parietal N20 potential to the prerolandic frontal area. AB - Somatosensory evoked potentials were recorded from the frontal and parietal areas in patients with various lesions in the central nervous system on stimulation of the median nerve. Five representative cases who showed a selective loss of the positive potential from the frontal area are reported. In each case, the parietal N20 potential was relatively well preserved, and the midposition between the frontal and central areas (FC area) showed a negative potential following P14. The peak of this negative potential was synchronous with that of the parietal N20 potential. This negativity on the FC area is considered to be a volume conducted potential from the parietal N20 to the prerolandic frontal area. Such an anterior volume conduction of the parietal N20 would not be explained by the concept of a tangentially oriented dipole generated in the posterior bank of the central sulcus. Instead, for the generator of the parietal N20 potential, a radically oriented dipole generated mainly in the parietal area is postulated. PMID- 2245309 TI - X-linked dominant hereditary motor and sensory neuropathy. AB - Modern techniques have defined the hereditary motor and sensory neuropathies (HMSN) as a genetically heterogeneous group of disorders. This includes a rare variant with X-linked dominant inheritance. We have traced this disorder through 6 generations of a large Canadian kindred; neurological and electrophysiological examinations were performed in 57 family members and nerve biopsies were studied in 2 affected males, early and late in the disease; 42/83 family members were affected. No male-to-male transmission was encountered in 19 sons of affected fathers, whereas all their daughters expressed the disease. Linkage was shown to the DNA loci DXYS1 Z max = 2.87 at theta max = 0.06 and to PGK1 Z max = 1.51 at theta max = 0 (Beckett et al., 1986). The typical clinical features are onset in early childhood, pes cavus, atrophy and weakness of peroneal muscles and intrinsic hand muscles, and sensory abnormalities. Males were severely affected, whereas females had mild or subclinical disease. Electrophysiological observations indicated a substantial loss of distal motor and sensory nerve fibres. Evoked compound muscle action potentials in extensor digitorum brevis were absent or severely reduced in 42% of cases and the peroneal motor nerve conduction velocity was mildly reduced to a mean 36.5 +/- 7.4 m.s-1. Sural sensory nerve action potentials were absent or severely reduced in 75% of those affected. Nerve biopsies showed loss of myelinated and unmyelinated nerve fibres, regenerative sprouting and secondary demyelination. The findings indicate that this distinct variant of HMSN is the result of primary axonal degeneration. PMID- 2245310 TI - Selective spatial attention in patients with visual extinction. AB - The present study was designed to verify the attentional performance of patients with parietal lesions in the experimental condition in which they had to pay attention to 3 spatial positions located on the left, on the right and directly above the fixation stimulus (Experiment 1) and to only 1 of the 3 spatial positions at a time (Experiment 2). Twelve patients (6 subjects with right parietal lesions and 6 subjects without neurological deficits) participated in the experiment. The results of Experiment 1 showed that in patients with right parietal lesions the speed and accuracy of response to horizontally aligned stimuli increased gradually from right to left, whereas the control group showed only the effect due to the different retinal eccentricities of the 3 stimuli, that is, responses to central stimuli were faster and more accurate than responses to left and right stimuli. The results of Experiment 2 showed that both the neurological and control groups were faster to respond to central than to left and right stimuli, and that the neurological group was faster to respond to right than left stimuli, whereas no difference in RTs between two visual fields was obtained in the control group. Furthermore, when the patients had to respond to 3 spatial locations aligned horizontally (Experiment 1), the speed and accuracy of response to the right stimulus were the same as when they had to focus attention on it (Experiment 2). These results showed that the focus of attention in patients with visual extinction is on the rightmost stimulus and that the increased attention to the right is accompanied by a decreased attention to the left. PMID- 2245311 TI - Voluntary activation of human motor axons in the absence of muscle afferent feedback. The control of the deafferented hand. AB - The ability to activate human motoneurons supplying individual intrinsic muscles of the hand was examined during acute deafferentation of the muscles. Tungsten microelectrodes were inserted percutaneously into motor fascicles of the ulnar nerve of 5 subjects, which was then blocked distally with local anaesthetic. In 4 subjects unitary action potentials were recorded from 16 motor axons, which were identified with respect to their target muscles. In the complete absence of muscle afferent feedback, subjects could voluntarily recruit motoneurons, grade their discharge and sustain a constant level of activity. Significant facilitation of motor efforts was provided by cutaneous feedback from the digits via the median nerve. During attempted maximal voluntary efforts the mean discharge frequencies of single motor axons were significantly lower than those of normally-innervated motor units. This finding suggests that peripheral afferents have a net facilitatory influence on motoneurons. However, during prolonged (20-30 s) maximal voluntary efforts the deafferented motoneurons did not display the progressive decline in discharge frequency shown by normally innervated motor units during contractile fatigue, a finding consistent with two possible explanations: disfacilitation or reflex inhibition of the motoneuron pool by peripheral afferents. The results also indicate that the otherwise intact nervous system can perform some simple motor tasks with no proprioceptive input other than knowledge of the motor commands. Other factors may contribute to the poor motor performance reported for patients with severe sensory deficits. PMID- 2245312 TI - Responses of the optic tectum to telencephalic stimulation in catfish. AB - In order to test physiologically for cerebrotectal connections in a fish, averaged evoked potentials and unit responses were recorded from the optic tectum following electrical stimulation applied to the telencephalon in the siluroid teleost Ictalurus nebulosus. A single shock applied to the area dorsalis centralis (Dc) of the telencephalon, and only to this area, elicits a sequence of deflections in the ipsilateral optic tectum: an initial negative peak at about 8 ms, (= N8), a larger N25 and a slow P50-N95. The configurations, depth profiles, latencies and susceptibility to repetitive stimulation, together with the known tectal anatomy, suggest that the first wave is due to the afferent fibers from the telencephalon and that N25 is due to deep tectal neurons. Telencephalic input exerts a conditioning effect on the field potentials and unit responses evoked by direct optic nerve shock. Such a shock elicits, in the contralateral tectum, small negative, optic tract axon peaks followed by a large N6, believed to be postsynaptic, and a still later P12. As a first approximation it is argued that the telencephalic input and the retinal input are activating different sets of neuronal elements in the optic tectum, since the configuration and depth profile of the telencephalic and optic nerve shock-elicited potentials are different. A conditioning Dc stimulus has a long-lasting effect on the form of the optic nerve field potential, maximally when the pallial shock precedes the optic by about 90 ms. The effect, observed by subtracting the conditioned from the unconditioned tectal response to optic nerve shock, is a difference wave with N11 and P20. The unit activity from deep tectal laminae is either activated or accelerated following Dc stimulation, while superficially located neurons are not affected. In another group of tectal units, the optic nerve shock-induced response is depressed by a preceding pallial dorsalis centralis stimulus. The evidence is compatible with the assumption of direct projections from Dc to the deep layers of the tectum, but the timing could also permit indirect pathways. In any case, the influence is not simple or identical for different tectal cell classes. PMID- 2245313 TI - Neurogenesis in a marsupial: the brush-tailed possum (Trichosurus vulpecula). I. Visual and auditory pathways. AB - The times of origin of neurons in the visual and auditory systems were studied in a marsupial, the brush-tailed possum, using tritiated thymidine autoradiography. Within the subcortical visual pathways, most neurons are generated between postnatal days 5 and 21, and the neurons of the primary visual cortex up to postnatal day 68. In the subcortical auditory pathways, most neurons are generated between postnatal days 5 and 28, and all auditory cortex neurons have appeared by postnatal day 46. Neurons in a single layer of cerebral cortex are generated during a period of about 2 weeks. Thus cortical neurogenesis in marsupials extends over a period similar to that seen in primates. PMID- 2245314 TI - Neurogenesis in a marsupial: the brush-tailed possum (Trichosurus vulpecula). II. Sensorimotor pathways. AB - The times of origin of neurons in sensorimotor pathways of the marsupial brush tailed possum were determined with 3H-thymidine autoradiography. A series of 20 possums were injected with 3H-thymidine from postnatal days 5-95 and were normally allowed to survive until the brain cytoarchitecture was mature. Brain stem and spinal sensorimotor regions were not labelled in our study and presumably form before birth in order to enable the newborn young to make the journey from the birth canal to the pouch on its own. Neurogenesis in thalamic sensorimotor nuclei probably begins about the time of birth and continues into the 2nd week of postnatal life. Formation of neurons in the sensorimotor cortex and the basal ganglia occurs during the first 2 months of postnatal life and in the cerebellum during the first 3 months. This protracted postnatal development of telencephalic and cerebellar sensorimotor regions offers great advantages for developmental studies. PMID- 2245315 TI - Functional analysis of sexual dimorphism in an electric fish, Hypopomus pinnicaudatus, order Gymnotiformes. AB - Hypopomus pinnicaudatus, an electric fish, has a marked sexual dimorphism in its tail filament. Sexually mature males have long, 'feathered' tails as compared with females. The sexual dimorphism emerges when a fish reaches about 110 mm total length. Mature males have larger electrocytes which are more widely spaced and more numerous than those in mature females. The biphasic electric organ discharge (EOD) is longer in males than in females. The peak-to-peak amplitude of the male's EOD is weaker than a female's of the same total length. The weaker discharge is unexpected given the increase in size and number of electrocytes. It is suggested that the reduction in EOD amplitude is a consequence of the increase in EOD duration among males. Further, female choice probably played a role in the evolution of long duration EODs among males, and males may have secondarily grown long tails to compensate for the loss in active space that would otherwise accompany a weaker EOD. PMID- 2245316 TI - Heritability and association of cortical petalias in rhesus macaques (Macaca mulatta). AB - Frontal and occipital petalias, the anterior or posterior protrusions of a cerebral lobe on one side or the other, are among the most striking anatomical asymmetries in human brains. Our previous studies of rhesus macaques revealed a relatively high frequency of right frontal petalias, whereas occipital petalias were seen less often and were equally common on right and left sides. In the present study, we test the hypothesis that variation in frontal and occipital lobular morphology is, in part, genetically based, and that frontal and occipital petalias are associated with one another. With a sample of 403 rhesus macaque endocasts, we found that right frontal petalias were more commonly associated with left occipital petalias than would be expected by chance. The concurrence of right frontal and left occipital petalias is the most common variant in human brains. We also found significant but moderate heritability for frontal petalias, while the heritability estimate for occipital petalias was relatively low and not statistically significant. This result suggests a genetic basis for variation in the degree of anatomical cerebral lateralization. PMID- 2245317 TI - NGF-induced remodeling of mature uninjured axon collaterals. AB - Accumulation of nerve growth factor (NGF) within the rat hippocampus following septal denervation is thought to contribute to sympathetic axon ingrowth. However, intraventricular NGF infusion, which results in elevated hippocampal NGF, fails to elicit such sprouting, although it increases innervation of the extracerebral vasculature. To determine whether or not NGF would stimulate sympathohippocampal sprouting, we infused NGF after sprouting was initiated. Surprisingly, NGF reduced the amount of hippocampal sprouting and, when infused at the time of lesion, delayed its onset while, at the same time, stimulating perivascular sprouting. Since NGF did not prevent ingrowth into the hippocampus from transplanted sympathetic ganglia, the reduction in sympathetic hippocampal fibers from intact ganglia appears to result from the proliferation of vascular fibers. Thus, changes in trophic support (NGF levels) appear to be sufficient to produce remodeling of mature, uninjured sympathetic arbors. Such trophomorphism may underlie collateral elimination during normal development and injury-induced neuronal rearrangements. PMID- 2245318 TI - Further studies of the effects of intranigral morphine on behavioral responses to noxious stimuli. AB - Bilateral intranigral microinjection of morphine produces dose-related and naloxone reversible analgesic-like effects on the hot-plate and tail-flick tests. The main objectives of the present studies were to further characterize the analgesic-like effects of intranigral morphine, to determine whether these effects were related to a general impairment of sensory or motor function, and to assess their anatomical specificity. The principal findings are: (1) intranigral morphine (10 micrograms) suppresses pain-related behavior without altering responses to a variety of non-noxious auditory, visual, and somatic stimuli, and without producing motor impairment; (2) movement of injector needles approximately 1 mm rostral, dorsal, or medial to the active nigral site significantly reduces the analgesic-like effect of morphine on the tail-flick test; and (3) electrolytic lesions confined to the nigra significantly reduced the analgesic-like effect of morphine on the hot-plate test. It is concluded that the analgesic-like effects of intranigral morphine are mediated by the substantia nigra and that these effects are specifically related to pain. PMID- 2245319 TI - Coexistence of parvalbumin and glycine in the rat brainstem. AB - The coexistence of glycine- and PV-immunoreactivities was studied immunocytochemically in the nuclei of the superior olive, trapezoid body, cochlea and lateral lemniscus. All of the PV-immunoreactive neurons in the nuclei of the superior olive and trapezoid body were immunoreactive to glycine but not to GABA. In the dorsal cochlear nucleus, PV-positive neurons were sometimes immunoreactive to glycine. In the ventral nucleus of the lateral lemniscus, PV-positive cells were immunoreactive neither to glycine nor to GABA. Consequently, it was concluded that PV-immunoreactivity was distributed not only in the GABAergic neurons, but also in the glycinergic neurons and possibly in wider neuronal populations. PMID- 2245320 TI - The influence of peripheral connections on wallerian degeneration. AB - Following electrophysiological techniques we investigated whether wallerian degeneration of the cat sural nerve may be influenced by (1) its peripheral connection and (2) the distance from the cell body. Distal stumps connected to their innervation sites peripherally showed less degeneration than proximal ones when isolated between two sections. However, when two isolated adjacent segments were produced by making 3 sections, the resulting degeneration was more pronounced in the distal segment. Thus, both the factors mentioned above appear to influence wallerian degeneration. PMID- 2245321 TI - Intra-accumbens implants of embryonic dopaminergic neurons reverse the behavioral supersensitivity to opiates evoked by lesion of the mesolimbic dopaminergic pathway. AB - The ascending mesotelencephalic dopaminergic systems of rat pups of 3 days of age were bilaterally lesioned using 6-hydroxydopamine injected at the level of the lateral hypothalamus. A sub-group of lesioned pups received, 5 days after the lesion, a dopamine neuron-rich cell suspension graft implanted bilaterally into the striatum and nucleus accumbens. Behavioral tests were conducted 6 months later. The lesion induced an increase in the locomotor activation induced by D Ala2-Met5-enkephalinamide injected into the nucleus accumbens (2.5 micrograms/side) as compared to the activation observed in control animals. Locomotor activation by systemic apomorphine (0.1 mg/kg s.c.) was also increased while that induced by amphetamine (1.5 mg/kg i.p.) was abolished. The presence of DA neuron implants reversed each of these post-lesion modifications. PMID- 2245322 TI - Differential stimulus coupling to dopamine and norepinephrine stores in rabbit carotid body type I cells. AB - Recent studies suggest that preneural type I (glomus) cells in the arterial chemoreceptor tissue of the carotid body act as primary transducer elements which respond to natural stimuli (low O2, pH or increased CO2) by releasing chemical transmitter agents capable of exciting the closely apposed afferent nerve terminals. These type I cells contain multiple putative transmitters, but the identity of the natural excitatory agents remains an unresolved problem in carotid body physiology. Characterization of putative transmitter involvement in the response to natural and pharmacological stimuli has therefore become fundamental to further understanding of chemotransmission in this organ. The present study demonstrates that a natural stimulus (hypoxia) evokes the release of dopamine (DA) and norepinephrine (NE) in approximate proportion to their unequal stores in rabbit carotid body (DA release/NE release = 8.2). In contrast, nicotine (100 microM), a cholinomimetic agent thought to act on the nicotinic receptors present on the type I cells, evokes the preferential release of NE (DA release/NE release = 0.17). These findings suggest that distinct mechanisms are involved in a differential mobilization of these two catecholamines from the rabbit carotid body. PMID- 2245323 TI - Three-dimensional form and a simple, interrupted flat map of a single layer in the lateral geniculate nucleus of the cat. AB - A simple, computer-based procedure is described for measuring the 3-dimensional (3D) coordinates and making two-dimensional (2D) flat maps of a curved surface representing the middle depth of layer A1 in the lateral geniculate nucleus (LGN) of the cat. The surface was defined from histological sections and flattened by tiling it with small triangular tiles which were then laid in a single plane to form several flat strips or lunes. Though the resultant maps are discontinuous (interrupted), they preserve total area to within a few percent, have constant scales throughout and closely approximate true shape within individual tiles. The results represent a step in assessing the potential contribution of form to visual function in the LGN. They provide graphic 3D and 2D images of the complex shape of a single layer and a quantitative framework for constructing models of geniculocortical processing that can incorporate the 3D form of the LGN as well as other anatomical and physiological data. PMID- 2245324 TI - Tritium quench in autoradiography during postnatal development of rat forebrain. AB - Quantitative autoradiography of tritium-labeled brain tissue requires correction for regional and age-dependent changes in tritium quenching. Correction values are determined using chloroform extraction of brain sections labeled with tritiated 2-deoxyglucose ([3H]2DG) in adult rats and rats at postnatal ages of 5, 14 and 21 days. Conditions are described for intraperitoneal injection of [3H]2DG for labeling neonatal animals which maximize the formation of [3H]2-deoxyglucose 6-phosphate. Tritium quench correction coefficients are determined in 65 brain regions at each age. Autoradiographic tritium quench increases during postnatal development in all brain regions, with the rate and extent of change corresponding to the development of myelination in different structures. Quench coefficients range from 6 to 45% in 5 day animals and from 21 to 108% in adult animals. Gray matter structures have a major increase in tritium quenching between postnatal days 5 and 14. Quench coefficients in white matter-containing structures increase throughout postnatal development at region-specific rates. These data may be used to correct regional differences in tritium quenching for autoradiographic studies of postnatal development. PMID- 2245325 TI - Dispersed cell suspensions of fetal SCN restore circadian rhythmicity in SCN lesioned adult hamsters. AB - Overt circadian rhythms are permanently disrupted following lesions of the suprachiasmatic nucleus (SCN) in hamsters. It has previously been demonstrated that whole tissue grafts which include the fetal SCN restore circadian locomotor rhythms to hamsters previously made arrhythmic by SCN lesions. In the present study, we ask whether the intrinsic peptidergic organization of the SCN is a prerequisite for functional recovery of circadian rhythms of locomotor activity. To this end, dispersed cell suspensions of [3H]thymidine-labelled fetal anterior hypothalamic tissue which contains the SCN, were injected stereotaxically into the brain of adult hamsters. Dispersed cell suspensions restored free-running locomotor rhythms, but not entrainment or gonadal regression. The period of the restored free-running rhythms following injections of SCN cell suspensions was shorter than 24 h, in contrast to intact hamsters and SCN-lesioned hamsters whose rhythms are restored by whole tissue grafts. In animals with restored rhythms, a majority of [3H]thymidine-labelled cells were located within nuclei of the midline thalamus and zona incerta. In a few individuals, donor cells were also deposited along the injection tract as far ventrally as the medial hypothalamus. Restoration of free-running locomotor rhythmicity was correlated with the presence of small numbers of isolated VIP cells along with small plexuses of VIP fibers. In animals which did not recover locomotor rhythmicity, grafts were identical in location and size to those in recovered hamsters, but did not contain peptidergic cells characteristic of the SCN. The results suggest that structural integrity of the fetal SCN is not necessary for restoration of rhythmicity after grafting. PMID- 2245326 TI - A morphometric analysis of isolated Torpedo electric organ synaptic vesicles following stimulation. AB - The electric organ of Torpedo has been stimulated with 1800 pulses at 0.1 Hz to produce biochemical and morphological heterogeneity of its synaptic vesicle population. This was verified by biochemical and morphometric analyses of the synaptic vesicle population isolated by sucrose density gradient zonal separation following stimulation. Biochemical or metabolic heterogeneity was verified using 2 established criteria: the appearance of a second peak of acetylcholine (ACh) in denser fractions of the zonal gradient and a corresponding overlapping peak of incorporated radiolabelled ACh. Morphologic heterogeneity was deduced by the presence in this second peak of a subclass of synaptic vesicles having a mean diameter of 68 nm i.e., a diameter 20-25% smaller than the 90 nm subclass that represents the most prominent subclass of the intact terminal population. Despite having satisfied these 3 criteria, functionally relevant heterogeneity cannot be assumed. One reason is due to our failure to recover the 90 nm subclass of vesicle which provides the physical basis to explain the 2 ACh peaks along the gradient. Because of this, the point is raised whether the stimulation-induced ACh peak is not merely an artifact due to inadequate sampling. On the other hand, radioactive labelling of the ACh pool provides a more convincing demonstration of the existence of 2 metabolically different subclasses. We conclude that morphological heterogeneity of the ACh vesicle population has never been established and that metabolic heterogeneity, as it has been studied to date, pertains to a single-sized subclass population of vesicles measuring 68 nm in diameter. PMID- 2245327 TI - Neuronal damage and calcium accumulation following repeated brief cerebral ischemia in the gerbil. AB - We investigated the distribution of neuronal damage following brief cerebral transient ischemia and repeated ischemia at 1-h intervals in the gerbil, using light microscopy and 45Ca autoradiography as a marker for detection of ischemic damage. The animals were allowed to survive for 7 days after ischemia induced by bilateral carotid artery occlusion. Following 2-min ischemia, neuronal damage determined by abnormal calcium accumulation was not observed in the forebrain regions. Following 3-min ischemia, however, abnormal calcium accumulation was recognized only in the hippocampal CA1 sector and part of the striatum. Two 2-min ischemic insults caused extensive abnormal calcium accumulation in the dorsolateral part of striatum, the hippocampal CA1 sector, the thalamus, the substantia nigra and the inferior colliculus. The ischemic insults were more severe than that of a single 3-min ischemia. However, three 1-min ischemic insults caused abnormal calcium accumulation only in the striatum. On the other hand, three 2-min ischemic insults caused severe abnormal calcium accumulation in the brain. The abnormal calcium accumulation was found in the dorsolateral part of striatum, the hippocampal CA1 sector, the thalamus, the medial geniculate body, the substantia nigra and the inferior colliculus. Gerbils subjected to three 3-min ischemic insults revealed most severe abnormal calcium accumulation. Marked calcium accumulation was seen not only in the above sites, but also spread in the neocortex, the septum and the hippocampal CA3 sector. Morphological study after transient or repeated ischemia indicated that the distribution and frequency of the neuronal damage was found in the sites corresponding to most of the regions of abnormal calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245328 TI - Reversible inactivation of the medial septum differentially affects two forms of learning in rats. AB - The contribution of the medial septum to different aspects of spatial information processing was assessed by examining the effects of reversible septal inactivation on radial maze performance of rats. In addition, the selectivity with which the medial septum affects learning was studied by testing the effects of septal inactivation on the acquisition of non-spatial information. Rats were first trained according to a spatial working memory procedure that included a 30 min delay between the first 4 (forced) choices and subsequent test (free) choices. The forced choices comprised the sample phase of the experiment while the free choices comprised the test phase. Saline or tetracaine (a local anesthetic) was injected into the medial septal area either before the sample phase, after the sample phase (i.e. at the beginning of the delay period), or just before the test phase. In contrast to the saline injections, tetracaine injected just before the sample or test phases produced a significant increase in errors at test. Tetracaine injection at the beginning of the delay period did not affect test choice accuracy. EEG records showed that septal inactivation drastically, yet temporarily, reduced the hippocampal theta rhythm. Thus, when septal inactivation occurred either before the sample phase or at the beginning of the delay period, hippocampal theta recovered by the time of the test phase. Septal inactivation also produced a significant retardation of learning on a non spatial reference memory task, although clear improvement over trials did occur. Moreover, the results of subsequent saline injections suggest that at least some of the performance deficit was due to variables other than learning per se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245329 TI - Auditory response properties and directional sensitivity of cerebellar neurons of the echolocating bat, Eptesicus fuscus. AB - Auditory response properties and directional sensitivity of cerebellar neurons of Eptesicus fuscus were studied under free-field stimulation conditions. The best frequency (BF) and minimum threshold (MT) of a recorded neuron were first determined with a sound delivered in front of the bat. Discharge pattern and MT were studied with both BF stimuli and one-octave downward and upward sweep FM (frequency-modulated) stimuli. The directional sensitivity of cerebellar neurons was then studied by determining the variation of MT and response latency with BF and FM stimuli broadcast from each of 15 loudspeakers attached to a semicircular wooden track in front of the bat. All 85 cerebellar neurons recorded discharged phasically to acoustic stimuli. Only 20 were spontaneously active. Cerebellar neurons were generally more sensitive to FM stimuli than to pure tone pulses. Thus, they discharged more vigorously and had a lower MT to the former than the latter stimulus. Directional sensitivity of 47 neurons (BF = 23.4-81.1 kHz) was studied. All neurons varied their MTs with sound direction. Most neurons (n = 37, 79%) showed a lowest MT to a frontal sound. Directional sensitivity of cerebellar neurons appears to be sharper when determined with BF tone pulses than with FM stimuli. Thus the directional slope and the difference in MT between the best and worst angles of these neurons were larger when determined with the BF stimulus. Directional sensitivity of cerebellar neurons is not dependent upon stimulus frequency, unlike that of the inferior and cortical neurons of the same bat. Cerebellar neurons also varied their response latency with sound direction. Such a variation may provide the bat with another neural code for sound localization. PMID- 2245330 TI - An unusually small potassium current that is well-suited to a retinal neuron which is chronically depolarized. AB - Here we describe a sustained outward potassium current (IK) in retinal horizontal cells (HCs). IK is unusually small over the range of membrane potentials normally experienced by these cells, which are chronically depolarized. We hypothesize that this unique IK will reduce the amount of neurotransmitter required to shift the cell's membrane potential over a wide range, and will minimize the redistribution of potassium ions across the post-synaptic membrane when the cell is depolarized. PMID- 2245331 TI - Injection of prostaglandin E2 into the anterior hypothalamic preoptic area activates brown adipose tissue thermogenesis in the rat. AB - E series prostaglandins (PGE) are known to elicit potent hyperthermia when injected into the anterior hypothalamic preoptic area (POAH) in rats, but the effector mechanisms mediating the rise in temperature are not well defined. In the present study, microinjection of PGE2 into the POAH dose-dependently increased non-shivering thermogenesis in brown adipose tissue (BAT) in urethananesthetized rats, bringing about a marked and sustained rise in interscapular BAT (IBAT) and core temperatures. The effect of intra-POAH PGE2 injection on IBAT and core temperatures could be blocked by systemic pretreatment with the sympathetic ganglionic blocker chlorisondamine chloride or the beta adrenergic receptor blocker propranolol, thus implicating the involvement of the sympathetic system. Furthermore, the increase in IBAT and core temperatures induced by intra-POAH PGE2 could be blocked by prior injection of the local anesthetic procaine or the GABA receptor agonist muscimol into the ipsilateral ventromedial hypothalamic nucleus (VMH). Taken together, the results suggest that PGE2 increases body temperature by acting in the POAH to stimulate heat production in BAT via a sympathetic efferent mechanism located in the VMH. PMID- 2245332 TI - Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology. AB - Stimulation of astroglial 5-HT1A receptors causes astroglial cells to acquire a more mature morphology and to release a factor (or factors) which promotes growth of serotonergic neurons. By using an antibody-blocking approach, we have shown that at least one of the growth-promoting factors thus released is the astroglial specific protein S-100. This may be a particularly important observation, in view of studies implicating S-100 in both Down's syndrome and Alzheimer's disease. PMID- 2245333 TI - Call and skin glands secretion induced by stimulation of midbrain in urodele (Andrias davidianus). AB - Stimulation of the midbrain induced calls, gaping, tail lashing, locomotion and secretion of skin glands in the cryptobranchidae, Andrias davidianus, which is a rare precious animal in China. These responses can be considered as a complex of action related to escape. Most of the sites where calls and secretion of skin glands could be induced were found in the outside of central nucleus of the torus semicircularis. This is the first description of this cluster of functions in the midbrain of Andrias davidianus. PMID- 2245334 TI - Interleukin-1 affects the behavioral despair response in rats by an indirect mechanism which requires endogenous CRF. AB - Interleukin-1 (IL-1) administered intracerebroventricularly (i.c.v.) to rats significantly reduces the level of immobility in animals forced to swim in a confined space. Immunoneutralization of endogenous CRF (corticotropin-releasing factor) by i.c.v. administration of CRF-antiserum prevents the IL-1-induced sinking in rats. This shows that the release of cerebral CRF, probably from the hypothalamus, may mediate the behavioral effect promoted by IL-1. Taken together our results suggest the existence of a complex interface between immune, neuroendocrine and behavioral regulation. PMID- 2245335 TI - Ablations of areas 3a and 3b of monkey somatosensory cortex abolish cutaneous responsivity in area 1. AB - Cortex traditionally referred to as S-I in monkeys is a composite of 4 separate and complete representations of the contralateral body surface, one in each of the 4 cytoarchitectonic fields, areas 3a, 3b, 1 and 2. We investigated the significance of interconnections between these architectonic areas by assessing the immediate effects of ablations of parts of areas 3a and 3b on the responsivity of neurons in area 1. Ablations of specific parts of the hand representations in areas 3a and 3b immediately deactivated the corresponding part of the hand representation in area 1. We conclude that the processing of somesthetic inputs across anterior parietal cortex is predominantly hierarchical. PMID- 2245336 TI - Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer's disease. AB - Melatonin and 5-methoxytryptophol (ML) were measured in human pineals (38 controls, 16 subjects with Alzheimer's disease). Time of death had a major influence on the indole concentrations with significantly higher melatonin levels occurring at night (22.00-10.00 h) and significantly higher ML levels occurring during the day (10.00-22.00 h). This daily variation disappeared in both the older subjects (55-92 years) and in the Alzheimer patients (55-89 years). PMID- 2245337 TI - 'Ischemic tolerance' phenomenon found in the brain. AB - We investigated the possibility that neuronal cells given a mild ischemic treatment sufficient to perturb the cellular metabolism acquired tolerance to a subsequent, and what would be lethal, ischemic stress in vivo. Cerebral ischemia was produced in the gerbils by occlusion of both common carotids for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. Minor 2-min ischemia in this model depletes high-energy phosphate compounds and perturbs the protein synthesis, but never causes neuronal necrosis, and therefore was chosen as mild ischemic treatment. Single 2-min ischemia 1 day or 2 days before 5 min ischemia exhibited only partial protective effects against delayed neuronal death. However, two 2-min ischemic treatments at 1 day intervals 2 days before 5 min ischemia exhibited drastically complete protection against neuronal death. The duration and intervals of ischemic treatment, enough to perturb cellular metabolism and cause protein synthesis, were needed respectively, because neither 1-min ischemia nor 2-min ischemia received twice at short intervals exhibited protective effects. This 'ischemic tolerance' phenomenon induced by ischemic stress--which is unquestionably important--and frequent stress in clinical medicine, is intriguing and may open a new approach to investigate the pathophysiology of ischemic neuronal damage. PMID- 2245338 TI - Methylxanthines elevate reinforcement threshold for electrical brain stimulation: role of adenosine receptors and phosphodiesterase inhibition. AB - Caffeine increases reinforcement threshold in a brain stimulation procedure that allows the rat to self-regulate the intensity of electric current delivered via an electrode in the medial forebrain bundle. In order to determine the generality of that finding, we used this same autotitration procedure to assess the behavioral effects of 5 methylxanthines in addition to caffeine. All of the methylxanthines produced significant dose-dependent elevations of reinforcement threshold with the following order of potency: 7-(beta-chloroethyl)theophylline greater than isobutylmethyl-xanthine greater than 1,7-dimethylxanthine greater than theophylline greater than caffeine greater than 8-chlorotheophylline. This order of potency correlates significantly with the reported order of potency for inhibiting adenosine-stimulated cAMP, an effect mediated by the adenosine A2 receptor. Some of the behavioral effects of methylxanthines have been attributed to antagonism of adenosine receptor binding and inhibition of phosphodiesterase. The nonxanthine phosphodiesterase inhibitors papaverine and Ro 20-1724, had small but significant effects on reinforcement threshold, papaverine increasing it and Ro 20-1724 decreasing it. Thus, as a pharmacologic class, methylxanthines appear to increase reinforcement threshold, an effect which may be mediated via adenosine receptor antagonism but probably not by inhibition of phosphodiesterase. PMID- 2245339 TI - Environmental influence on behaviour and nerve growth factor in the brain. AB - The influence of the environment on the endogenous levels of nerve growth factor (NGF) in the cortex, hippocampus and septum was examined in adult (82 days old) and juvenile (51 days old) rats. Animals were reared/housed for 30 days in an enriched, standard or isolated environment prior to analysis. In addition, another group of rats were given behavioural tests (4 days) after differential rearing/housing before measurements of NGF. We found complex variations in the level of NGF both in juvenile and adult hippocampus after differential environmental rearing/housing. Rearing/housing in an enriched environment improved performance in the Morris maze and decreased spontaneous motor activity. Exposure to behavioural tests caused alterations in adult hippocampus and septum NGF levels. The results show that testing in a novel environment causes small but significant changes in the hippocampal and septal NGF levels depending upon the environmental history of the animal. In view of the purported involvement of the septohippocampal pathway and NGF in the pathophysiology of Alzheimer's disease, our finding suggests that lack of adequate environmental stimulation might be of importance in age-related behavioural and neurochemical deficits. PMID- 2245340 TI - Effect of MK-801 on endogenous dopamine release in vivo. AB - The effect of MK-801 on striatal dopamine (DA) release was investigated by using an in vivo microdialysis technique in the freely moving rat. Systemic injection of MK-801 (0.25, 0.5, 1, 2 mg/kg, i.p.) reduced the extracellular level of DA significantly and produced no change in the level of 3,4-dihydroxyphenylacetic acid. The behavioral observation, recorded simultaneously, revealed that MK-801, with smaller doses, produced ipsilateral circling toward the side with the dialysis probe. At larger doses, MK-801 predominantly evoked ataxia. These findings indicate that the behavioral effect of MK-801 may not be mediated via the release of DA. PMID- 2245341 TI - Spinal block reveals roles for brain and spinal cord in the mediation of reflexive penile erections in rats. AB - Five experiments were addressed at two questions: (1) is the influence of the brain on spinal control of reflexive erection exclusively inhibitory; and (2) are the effects of copulation on erectile potential mediated by the brain, the spinal cord, or both? After various amounts of antecedent copulation, spinal anesthesia was induced in male rats by tetracaine (TET) injected through chronically implanted cannulae into the thoracic or lumbar spinal subarachnoid space, and the animals were then tested for reflexive penile erections (supine position, penile sheath retracted, no phasic stimulation applied). In sexually rested rats, TET injected at either T4 or T10 reduced reflex latency but also reduced the number and intensity of responses. Penile erection was inhibited by TET injected at L5, the region of the cord receiving sensory and motor projections from the genitalia. In previous studies surgical transection of the thoracic cord facilitated erection latency and production. In the present experiments the divergent effects of intrathecal TET on these variables suggested that they are controlled by separate systems within the spinal cord and that in the sexually rested rat the net influence of the brain is to inhibit the latency system and excite the production system. After rats copulated to sexual satiety, thoracic spinal block did not reverse the complete abolition of reflexive erections, establishing for the first time that copulation has direct inhibitory effects on the spinal cord's intrinsic system. Fewer antecedent ejaculations had less inhibitory effects on reflexive erection, and TET then acted, as in rested males, to reduce the erection latency and the number of erections, indicating that copulation may act on the brain's descending influences on spinal systems. The overall pattern of results suggested that the brain exerts both excitatory and inhibitory influences on separate, interacting spinal mechanisms that regulate the latency to reflexive erection and the number and intensity of erections displayed. PMID- 2245342 TI - Effect of light sources and light intensity on growth performance and behaviour of female turkeys. AB - 1. The effect of different light sources (incandescent, sodium vapour, daylight fluorescent and warm fluorescent) and light intensities (10.8 and 86.1 lux) on growth performance and behaviour of female turkeys was investigated in two experiments conducted at different times of the year. 2. Although light source influenced body weight and efficiency of food utilisation, there was no consistent effect between experiments in favour of any particular source. 3. Light intensity had no effect on body weight, efficiency of food utilisation or behaviour. PMID- 2245343 TI - Assessment of the effects of separate sex feeding on the welfare and productivity of broiler breeder females. AB - 1. The welfare and productivity of female broiler breeders were studied in pens containing 15 females and 1 male where the sexes were fed together or separately by means of a grid with 40 mm spaces over the female feeders. 2. Average head width did not increase after 25 weeks of age. 3. The rate of lay was lower in separate compared with mixed-sex-fed pens but egg weight was similar. 4. The incidence of swollen heads and beak lesions was higher and feather loss and rate of food intake was lower in separate compared with mixed-sex-fed pens. 5. It was concluded that the grid spaces should be 42 mm wide to avoid adverse effects on welfare and productivity. PMID- 2245344 TI - Test for linkage between the eumelanin dilution blue (B1), the extended black (E) allele at the E-locus and the linked pea comb (P) and eumelanin extension (M1) genes in the domestic fowl. AB - 1. A mating was made between a Blue Andalusian bantam male and a pea comb striped necked bantam female to produce a quadruple heterozygote of the linked pea comb (P) and eumelanin extension (Ml) genes and of the eunmelanin dilution blue (Bl) gene and the extended black (E) allele at the E-locus. 2. Two pea comb blue females so produced were mated to a single comb striped necked bantam male, thus providing a backcross to the quadruple recessive. 3. Bl segregated independently with each of the other three genes whilst 25 crossovers occurred amongst the 55 progeny assessed for linkage between P and Ml, confirming loose linkage between P and Ml which had previously been shown to be approximately 46 units. Linkage of 0.3% had been previously reported (Crawford, 1986) between P and a "melanotic" gene isolated from a segregating gene pool. Evidence is presented to demonstrate that two different "melanotic" genes were being considered, thus explaining the apparently contradictory reports. Charcoal (cha) is suggested for the recessive gene linked with P by 0.3%. 4. Thirty-four crossovers occurred among the 97 progeny between P and E suggesting linkage of approximately 35 units. A further mating was made from among segregants in the backcross which confirmed P-E linkage with 17 crossovers in 55 gametes. Combining the tests produced a linkage value of approximately 34 units. PMID- 2245345 TI - Evaluation of the dietary interaction of calcium and phosphorus in the high producing laying hen. AB - 1. In a 6 x 7 factorial experiment using 2688 22-week-old laying hens of the Lohmann-SL strain kept in cages (4 birds/cage), diets containing six calcium (20, 25, 30, 35, 40, 45 g calcium/kg) and seven phosphorus concentrations (3.2, 4.2, 5.2, 6.2, 7.2, 8.2, 16.2 g total phosphorus/kg (Pt)) were combined orthogonally. The resulting 42 treatments were replicated 8 times so that a replicate consisted of a double cage of 2 x 4 hens. The experiment lasted 40 weeks (10 x 28 days). 2. The experimental diets, based on maize and soyabean meals contained 11.5 MJ metabolisable energy/kg and 175 g/kg protein. Different dietary calcium and phosphorus contents were obtained by substituting oat hulls with limestone and dicalcium phosphate. 3. Mortality, egg production, egg weight, egg mass, food intake and food conversion efficiency were determined as well as the breaking strength, thickness of shells and the percentage of eggs with defective shells. 4. All responses measured were significantly influenced by the variance sources (calcium, phosphorus, interaction). Most of the production traits responded asymptotically to increasing dietary phosphorus concentration, the greatest increases or decreases generally being seen between 3.2 and 5.2 g Pt/kg. Further but weaker increases were seen between 5.2 and 8.2 or 16.2 g Pt/kg. 5. Increases in dietary calcium content always resulted in curvilinear responses. In all cases optimal effects were obtained with diets containing 25 g calcium/kg and the worst values at 45 g calcium/kg. The interaction between calcium and phosphorus was recognised by strong performance depressions and a high mortality at combinations of the lowest phosphorus concentration (3.2 g/kg) with high calcium contents (35 to 45 g/kg). These were largely offset by increasing dietary phosphorus. Thus, between 7.2 and 16.2 g Pt/kg and 25 and 45 g Ca/kg a plateau was formed where only small differences in egg production were observed. 6. From the three egg shell characteristics measured, breaking strength and shell thickness responded differently to the percentage of eggs with defective shells. While breaking strength and shell thickness were respectively negatively and positively influenced by increasing dietary phosphorus and calcium contents, both elements affected the proportion of eggs with defective shells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245346 TI - Nutritional effects on the growth and fatness of broilers. AB - 1. Broiler chickens given diets high in protein, or choice-fed on a high protein balancer, had much lower abdominal fat contents than those reported in many recent experiments. The values for males were 10.8 g/kg liveweight at 56 d at 2.43 kg liveweight in one experiment in Scotland and 16.0 g/kg liveweight at 42 d at 1.93 kg liveweight in another in South Africa. For females the values were 18.8 g/kg liveweight at 56 d at 2.15 kg liveweight in Scotland and 15.7 g/kg liveweight at 42 d at 1.60 kg in South Africa. 2. The content of abdominal fat was, in general, increased by reducing the protein content of the diet or by dilution of the food with oil or starch. It was, in general, reduced by diluting the food with dietary fibre which also reduced liveweight gain. 3. The results are consistent with the idea that chickens attempt to control their food intake so that they achieve a particular fatness. This level of fatness differs between the sexes and between degrees of maturity. PMID- 2245347 TI - Effect of dietary concentrations of fat and energy on fat deposition in broilers divergently selected for high or low abdominal adipose tissue. AB - 1. Fat deposition in abdominal, mesenterial, sartorial and gizzard adipose tissues (AT), liver, breast muscle, skin and carcase was studied in male broilers, selected for high (HF) and low (LF) abdominal fat and fed on diets differing in energy density and total fat content. 2. There were no significant differences in body weight in the experimental groups. The relative weight (g/kg body weight) of the dissected adipose tissues was higher in HF than in LF birds. Fat concentration in the AT (sartorial excepted), skin and body was higher in the HF compared with the LF birds. The lines did not differ significantly in liver and breast muscle fat content. 3. Abdominal AT was affected by selection or dietary fat more than other AT and total body fat. 4. In the HF birds increasing energy density from 12.3 to 13.4 MJ/kg (dietary fat kept constant: 5.46 g/MJ) significantly increased the weight of the abdominal, mesenterial and sartorial AT. Increasing dietary fat (at both energy densities) decreased the weight of the AT, whereas increasing both energy and fat did not affect it. In the LF birds, similar but milder and insignificant trends were observed. It is suggested that this interaction has biological significance. PMID- 2245348 TI - Protein and energy metabolism in broiler chickens selected for either body weight gain or feed efficiency. AB - 1. Correlated responses in protein and energy metabolism were studied in 2 lines of meat-type chickens selected during 6 generations for improved efficiency of food utilisation (line A) or greater body weight (line B). 2. Daily gain was 18% higher in line B but efficiency was 15% better in line A. 3. Metabolisability (ME/GE) was 0.752 in line A and 0.725 in line B. 4. Retained nitrogen as a fraction of nitrogen intake was 0.51 for line A and 0.46 for line B. 5. Energy retention as a fraction of metabolisable energy was 0.38 in line A and 0.43 in line B the difference being primarily attributable to greater fat retention in line B. 6. Selecting for improved efficiency of food utilisation in meat-type chickens having a growth capacity of 50 to 60 g was very effective and produced a lean bird with higher metabolisability of the diet. PMID- 2245349 TI - Reduced selenium status in chicks given diets low in sulphur-containing amino acids and containing sodium nitroprusside as a source of cyanide. AB - 1. Two experiments were carried out to study the effect of dietary cyanide, given in the form of sodium nitroprusside (SNP), on the growth and selenium status of chicks fed on diets low in sulphur-containing amino acids. 2. In experiment 1, SNP (0.3 g/kg) depressed growth rate and food intake when included in diets low in total sulphur-containing amino acids. It also reduced plasma and liver glutathione peroxidase activity (GSH-Px) and kidney selenium concentration. These latter variables also showed increases in response to supplements of selenium of 0.1 and 0.2 mg selenium/kg (as sodium selenite) although growth was not affected. 3. In experiment 2, SNP did not affect growth when reduced to 0.1 g/kg in diets low both in methionine and total sulphur-containing amino acids. It did, however, reduce plasma GSH-Px activity, which again increased in response to similar dietary supplements of selenium. 4. It is concluded that dietary cyanide effectively increases the requirement for selenium and could induce deficiency in diets only marginally adequate in selenium, particularly when the supply of sulphur-containing amino acids was marginal or inadequate. PMID- 2245350 TI - European reference method for the in vivo determination of metabolisable energy with adult cockerels: reproducibility, effect of food intake and comparison with individual laboratory methods. AB - 1. A common reference procedure adopted by several European laboratories to determine apparent metabolisable energy corrected to zero-nitrogen balance (AMEn) is described. 2. Reproducibility has been estimated by comparing results from 4 diets measured in 7 laboratories. The standard deviations between laboratories of dry matter, gross energy, Kjeldahl nitrogen and AMEn were respectively, on average, 11.29 g/kg, 0.242 MJ/kg, 1.56 g/kg and 0.380 MJ/kg dry matter; the corresponding coefficients of variation between laboratories were 1.27, 1.29, 4.39 and 2.92%. 3. Effect of food intake was tested by comparing AMEn from birds fed either 0.90 or 0.45 of ad libitum: the amount of food intake had a negligible effect on AMEn values. Endogenous energy losses corrected (EELn) or not (EEL) to zero nitrogen balance were estimated either by regression between excreted energy and ingested energy or in fasted and glucose-fed cockerels. EELn estimated by regression was, on average, 8.7 kJ/bird/d.; it was independent of diet composition. EEL and EELn determined in fasted or glucose-fed birds were higher than those determined by regression. 4. AMEn values measured by individual laboratory procedures were very close to those obtained by the reference method, except from laboratories using a tube feeding procedure, where deviations were probably a consequence of overestimated EEL. PMID- 2245351 TI - European reference method of in vivo determination of metabolisable energy in poultry: reproducibility, effect of age, comparison with predicted values. AB - 1. Apparent metabolisable energy corrected to zero-nitrogen retention (AMEn) was measured using the European reference procedure in 9 European laboratories. Seven pelleted diets were evaluated. AMEn was measured with adult cockerels and young birds. 2. Between-laboratory standard deviations were for dry matter (DM) 12.5 g/kg, gross energy 0.085 MJ/kg DM, Kjeldahl nitrogen 0.768 g/kg DM, AMEn (adults) 0.256 MJ/kg DM, and AMEn (young) 0.337 MJ/kg DM. Corresponding coefficients of variation between laboratories were 1.42, 0.45, 2.15, 1.88 and 2.60% respectively. 3. AMEn values of experimental diets were always significantly lower when measured with young birds. This effect was more pronounced when diets contained added fat. 4. Tallow or soyabean oil were incorporated into two basal diets at 40 g/kg inclusion rate. No significant differences were observed between AMEn values of either diet with adults or young birds, suggesting that AMEn energy values of these fats are indistinguishable at this inclusion rate. 5. Similar AMEn values were obtained in young birds by estimating nitrogen accretion, either by the difference between intake and excreta nitrogen or by measuring body weight gain. Determined AMEn values were very similar to those predicted using three different regression equations. PMID- 2245352 TI - The effect of dietary calcium upon growth rate, food utilisation and plasma constituents in lines of chickens selected for aspects of growth or body composition. AB - 1. The effect of increasing dietary calcium from 10.3 to 20 g/kg on 5- to 17-day growth performance and plasma minerals, electrolytes, total protein, albumin and glucose in chickens from 4 lines selected for: high 8-week body weight (W), low abdominal fat (L), high abdominal fat (F) or at random (C) was studied in two experiments. 2. High dietary calcium significantly reduced weight gain and plasma phosphate and potassium but increased food:gain ratio, plasma total calcium, glucose and albumin. 3. Significant correlations were found between plasma total calcium and plasma phosphate (r = -0.5, P less than 0.01), plasma total calcium and protein (r = 0.4, P less than 0.01) and between plasma total protein and albumin (r = 0.55, P less than 0.01). 4. Genotypes differed in their response to dietary calcium content. There was a substantial response in line F but little effect in line L. 5. In contrast to the three other lines, in line F high dietary calcium significantly increased plasma ionised calcium without altering plasma phosphate or total calcium concentration. 6. It was concluded that genetic selection has produced lines which vary in their tolerance to high dietary concentrations of calcium. Birds selected for increased fatness were less tolerant to high dietary calcium than their lean-selected counterparts. PMID- 2245353 TI - Effects of dietary calcium, available phosphorus and vitamin D on growth rate, food utilisation, plasma and bone constituents and calcium and phosphorus retention of commercial broiler strains. AB - 1. The effects of different dietary concentrations of calcium (Ca), available phosphorus (AP) and vitamin D (D) on 5- to 16-day growth performance, and aspects of calcium and phosphorus (P) metabolism of chickens from three commercial strains were studied in two experiments. 2. Increasing dietary Ca reduced weight gain, tibia Ca and P content and increased plasma total Ca, Ca consumption and excretion, whilst dietary Ca at 32 g/kg increased tibia Ca:P ratio, plasma ionized calcium and reduced plasma P, tibia ash, P excretion, excreta moisture and Ca retention. 3. Increasing dietary AP reduced plasma total and ionized Ca and excreta moisture and increased P consumption and excretion, plasma P and tibia ash. 4. The addition of vitamin D increased plasma total and ionized Ca, tibia Ca:P ratio and reduced plasma sodium and P concentrations. 5. Strains differed in their tibia contents of Ca and Ca:P ratios, in response to Ca, AP and vitamin D diets whilst they differed in Ca excretion and excreta moisture caused by feeding either dietary Ca or AP. 6. It was concluded that dietary Ca, AP, vitamin D and strain of broiler chickens influenced the metabolism of Ca and P and that, as a consequence, the tolerance to high dietary Ca. A lean strain of chickens tolerated high dietary calcium better than its fat counterparts. PMID- 2245354 TI - Pharmacokinetic aspects of a sulphachloropyridazine trimethoprim preparation in normal and diseased fowl. AB - 1. The pharmacokinetic and residue elimination patterns of sulphachloropyridazine appear to be modified by disease, even without affecting key organs essential for drug metabolism. 2. Drug kinetics and residue elimination data of a sulphachloropyridazine-trimethoprim preparation were compared using infectious coryza-affected (IC) fowl and healthy chickens. 3. The plasma concentrations of sulphachloropyridazine and trimethoprim were higher in affected animals, hence a reduced volume of distribution was obtained. 4. The half-life of sulphachloropyridazine and trimethoprim was reduced in IC-affected fowl and body clearance values were decreased. 5. The rate of drug residue elimination was noticeably slower in the IC-affected group. 6. These results indicate that drug elimination patterns in healthy and diseased animals are not the same. PMID- 2245355 TI - Storage of sperm in the uterovaginal junction and its incidence on the numbers of spermatozoa present in the perivitelline layer of hens' eggs. AB - 1. The numbers of spermatozoa found in the perivitelline layer (perivitelline spermatozoa) of hens' eggs during a 14-d period after insemination were found to be log-dose dependent (r = 0.99) on the quantities of spermatozoa inseminated intravaginally in these hens (50, 100, 200 or 400 million/female). 2. Highly significant correlations were also observed between the perivitelline spermatozoa and the proportion of uterovaginal sperm-storage tubules containing spermatozoa on day 14 after insemination. 3. These data confirm that the number of perivitelline spermatozoa in eggs laid on day 2 after artificial insemination (AI) are highly correlated with the mean percentages of fertility of its duration over a 14-d or 24-d period. As a consequence, eggs laid by the 10% highest or the 10% lowest females primarily classified on the basis of this variable exhibited on average 99% or 49.7% fertility, respectively, over a two-week period after AI. PMID- 2245356 TI - The response of broilers' adiposity to testosterone after embryonic exposure to androgen and tamoxifen. AB - 1. The effects of early exposure of heavy breed (HB) chicks to an anti-oestrogen (tamoxifen--TAM) and to an androgen which cannot be aromatised (5 alpha dihydrotestosterone--DHT) on subsequent adiposity and its response to testosterone were studied. 2. Embryonic TAM administration reduced adiposity in females but not in males at 8 weeks of age. Embryonic DHT produced similar responses but to a lesser extent. 3. Testosterone propionate (TP) administration during growth had no effect on adiposity in any of the treated groups but TP reduced adiposity in males which had been exposed to DHT at the embryonic stage. PMID- 2245357 TI - Arginine vasotocin and mesotocin in the anterior hypothalamus, neurohypophysis, proventriculus and plasma of White Leghorn cockerels, during dehydration. AB - 1. The effect of 96 hrs of water deprivation on plasma electrolytes, osmolarity, arginine vasotocin (AVT), mesotocin (MT), and on AVT and MT content in the neurohypophysis, anterior hypothalamic area (AHA) and proventriculus, was studied at 24 hrs intervals, in adult White Leghorn cockerels. 2. Plasma AVT increased three fold during the first 24 hrs but there was no further change during the next 48 hrs. In the last 24 hrs, plasma AVT decreased in about 25%. Plasma MT did not change during the entire period of dehydration. 3. Plasma sodium and osmolarity gradually increased during that time. 4. Neurohypophysial AVT content was depleted by 95% during the period of dehydration while MT content did not change. 5. In the AHA there was no change in AVT levels during dehydration while the levels of MT increased while in the proventriculus there was no change in either AVT or MT levels. 6. For the data collected during the entire experimental period, no correlation was found between plasma osmolarity and plasma AVT, but there was a highly significant negative correlation between plasma osmolarity and neurohypophysial AVT content. 7. It may be suggested that the depletion in AVT content in the neurohypophysis during progressive water deprivation resulted in an insufficient level of AVT in circulation to enable the cockerels to counter the dehydration. This may explain the death of those cockerels which were dehydrated for a further 24 hr period. PMID- 2245358 TI - Residues of macrolide antibiotics in eggs following medication of laying hens. AB - 1. The elimination kinetics of four macrolide antibiotics (tylosin, erythromycin, spiramycin and josamycin) in eggs were determined separately for albumen and yolk after oral administration through either drinking water or diet or after intramuscular injection. 2. Residues were assayed by a plate diffusion technique in cylinders with Micrococcus luteus as the test-organism. 3. Drug excretion was usually over a longer time in the yolk. Spiramycin was the most highly excreted in the egg whereas seven to eight times less tylosin and erythromycin was transferred. The conditions for the use of macrolide antibiotics in laying hens are discussed. PMID- 2245359 TI - Glossary of avian photoperiodic terminology and methods of expressing lighting regimens. AB - 1. A list of definitions is given for terms commonly used in animal photoperiodism. 2. A list of symbols and abbreviations commonly used in avian photoperiodism is included. 3. Methods are given for a standardised description of lighting regimens. PMID- 2245360 TI - Diagnosis and control of neonatal losses in sheep. AB - Perinatal mortality is affected by a variety of management factors and disease processes that create significant losses for the sheep industry. Annual production losses prior to weaning include roughly 15% to 20% of the lamb crop. The majority of these perinatal losses occur during the prenatal, natal, and early postnatal periods, with the predominant wave of mortality occurring during the first several days following birth. Causes of perinatal mortality may vary between flocks and between geographic areas; however, four dominant categories of lamb loss consistently surface: (1) abortions; (2) hypothermia, starvation, and exposure; (3) pneumonia; and (4) stillbirth and dystocia. They account for roughly 50% to 75% of all documented perinatal losses. Veterinarians and producers need to work together to document the type of losses that occur in a given flock and then design economic prevention programs that address these problems. In most cases, traditional prevention programs will need to be replaced by a comprehensive management scheme addressing nutrition, genetics, housing, marketing, lambing husbandry, and labor. PMID- 2245361 TI - Advances in sheep and goat medicine. PMID- 2245362 TI - Clinical nutrition of sheep and goats. AB - Management systems and client goals are integral components of clinical nutrition and vary among and within sheep and goat producers. Evaluation includes client interview and history taking, record examination, forage analyses, animal examination, and occasionally blood or tissue assays. The types of nutritional disorders that are likely to be observed in sheep and goats vary according to the type of management and can be grouped according to feedlot, intensive production, farm flocks, dairy, and browse systems. Examples described include nutritional problems that may be overlooked (water deprivation), widespread (energy imbalance), currently difficult to prevent and treat (selenium deficiency), and reflective of soil-plant-animal complexities (copper-molybdenum balance). PMID- 2245363 TI - Out-of-season breeding in goats. AB - Maintenance of winter milk production and the production of meat kids for seasonal specialty markets are two major reasons for out-of-season breeding. Strategies include the manipulation of light cycles and the administration of exogenous gonadotrophins following progestogen priming with either vaginal sponges or subcutaneous implants. A number of does in excess of expected need should be prepared. Excess numbers of bucks also are advisable, because libido and fertility often are lower out of season. PMID- 2245364 TI - The role of private practitioners in accelerated lambing. AB - Sheep producers throughout the United States have begun using accelerated lambing programs to enlarge their net income by increasing the number of lambs produced per ewe per year. These new intensive systems have produced some unique problems and concerns. This article attempts to educate the veterinarian as to the justification for these programs. Areas in which veterinary intervention can greatly influence the success or failure of these new accelerated lambing systems are identified. Selection of ewe type, ultrasound pregnancy diagnosis, ram evaluation, specific flock health concerns, and critical ewe nutrition are discussed. PMID- 2245365 TI - Use of ultrasonography in reproductive management of sheep and goat herds. AB - Real-time ultrasound evaluation of small ruminants offers an unparalleled range of information regarding pregnancy status, number of fetuses, and gestational age. The advantages of real-time ultrasonography are its sensitivity and accuracy of various diagnoses, its speed, and its safety. Overall flock reproductive management is facilitated through the timely acquisition of information with ewes culled, rebred, or preferentially fed, according to pregnancy status. Breeding dates of pasture-bred does can be assigned with sufficient accuracy to allow parturition induction at term without risk of severe immaturity in kids. Diagnoses other than pregnancy, such as pyometra, nydrometra, fetal resorption, and fetal mummification also can be made using real-time ultrasonography. PMID- 2245366 TI - Ventilation of sheep and goat barns. AB - Good ventilation is an important part of any livestock housing system. It may be accomplished by either natural or mechanical means. Generally, except for buildings that must be kept at warm, nonfluctuating temperatures, naturally ventilated cold housing is satisfactory for sheep and goats provided it is dry and draft-free in pen and resting areas, and air exchange is taking place at a rate high enough to remove moisture, gases, and airborne disease organisms from the building. Understanding the importance of site location, building orientation, and principles of ventilation design increases the likelihood of successful barn ventilation. PMID- 2245367 TI - Coccidiosis and cryptosporidiosis in sheep and goats. AB - The protozoan diseases, coccidiosis and cryptosporidiosis, are important enteric diseases of sheep and goats, resulting in diarrhea, inefficient weight gains, and occasionally death. Coccidiosis is a widespread, serious economic disease affecting animals who are preweaned, recently weaned, or in unsanitary, stressful, or crowded conditions, as well as after entering feedlots. The Eimeria species in sheep and goats are relatively host specific. Control is accomplished through sanitation and by incorporating one of the modern coccidiostats, such as lasalocid or decoquinate, in feed or salt to ensure an intake of approximately 1 mg of drug per kg of body weight per day for at least 30 consecutive days. Prevention and control of coccidiosis results in significantly greater weight gains and production, whereas disease with or without treatment is likely to result in inefficient production and economic loss to the producer. Cryptosporidiosis, caused by Cryptosporidium parvum, is primarily a disease of lambs and kids less than 30 days of age and is usually a milder disease than coccidiosis. Infective oocysts are passed in feces and are transmitted by oral ingestion. Oocysts readily infect a variety of animals, including humans. Cryptosporidiosis is a prevalent disease in neonatal ruminants and in humans. Effective treatments are not available, but because the disease is usually mild and self-limited, supportive care, primarily hydration, is important. Control is strict sanitation and quarantine of sick animals. Disinfection of contaminated housing with ammonia or formalin will kill the oocysts. The cyst-forming coccidia diseases, toxoplasmosis and sarcocystosis, utilize two hosts in their life cycles: sheep or goats and carnivores. Abortions and reproductive failures are major manifestations of disease. Control is through elimination of carnivore feces from the premises through management. PMID- 2245368 TI - Advances in the control of foot rot in sheep. AB - All cases of foot rot, whether acute, chronic, benign, or inapparent, must be identified. If the outbreak is severe and production losses warrant, each foot of each animal must be examined thoroughly. Proper handling facilities and equipment, adequate light, and dry working conditions are needed to properly examine each foot. Infected sheep must be separated from the clean flock. Following extensive treatment, these animals must be diagnosed as free from the disease before returning to the clean flock. Animals that do not respond must be culled from the flock. Although copper sulfate and formalin are effective materials for footbathing, zinc sulfate is equally effective and does not irritate the skin, eyes, or lungs as does formalin, or stain the wool as does copper sulfate. A 10% zinc sulfate solution with a nonionic surfactant is an effective footbathing or foot soaking solution. The cure rate is improved by a thorough foot paring and a foot soak of at least 30 minutes. A number of treatment options along with formulations are outlined in the 1988 edition of the Sheep Production Handbook of the Sheep Industries Development Program, Inc, 6911 Yosemite, Englewood, CO 80112. PMID- 2245369 TI - Epididymitis in rams and lambs. AB - This article reviews lamb epididymitis and epididymitis caused by Brucella ovis. Pathogenesis, occurrence, signs and lesions, diagnosis, prevention, and treatment are discussed. PMID- 2245370 TI - Exclusion of infectious diseases from sheep and goat farms. AB - It is important for practitioners and owners to be aware of the risk associated with an open herd. This article has discussed some of the infectious diseases that might be inadvertently introduced. Many others--including most exotic diseases and some that are regulated by governmental agencies, such as tuberculosis and brucellosis--have been omitted. It should be obvious that a simple health certificate is an inadequate guarantee of freedom from infections. Instead, producers should be prepared to invest both time and money in evaluating the health status of the herd of origin. Some of the diseases discussed, such as foot rot, cause tremendous financial losses. Others, such as pinkeye, can be easily "lived with." The point to be made is that producers should consider all these and other diseases and then make informed decisions based on the probable cost of these diseases if they became established in the herd. PMID- 2245371 TI - Special problems of hair goats. AB - The majority of Angora goats in the United States are in Texas, although several other states have significant populations. Angora goats have unique nutritional requirements, especially for protein, owing to their selection for mohair production. They are typically managed on extensive systems in which nutrition is marginal at certain times of the year. Mineral requirements and plant toxicities may vary between regions where Angora goats are raised. Many toxic plants are unpalatable and a problem only during times when animals are hungry and forced to eat them. Reproductive efficiency is notoriously low in Angora goats, for which a 50% kid crop weaned is average in many areas. This is due to some degree to poor nutrition and the associated stress abortions and birth of weak kids. Some Angora nannies are poor mothers and abandon their kids if distracted or frightened soon after parturition. Predators cause serious kid losses in many areas. Intensive management at kidding time can markedly increase the kid crop weaned. Freeze loss is a common problem in freshly shorn goats that are exposed to a rapid change in temperature and/or wind and rain. Because of the high protein requirement, the marginal dietary protein in many Angora diets, and the traditional raising of Angoras in arid regions where browsing of plants off the ground is typical, Angoras in wet regions that are forced to graze seem to be especially susceptible to internal parasitism with Haemonchus contortus. Coccidiosis can also be a severe problem in young Angoras that are congregated in small areas. Cashmere is not a specific breed of goat but rather a type of fine fiber produced by individuals of any breed of goat. Goats that have been selected for production of this fine, downy undercoat are referred to as "Cashmere" goats. In the United States, crossbreeding of Spanish (meat) goats to cashmere type bucks is being suggested as a way of producing an extra commodity from meat goat herds. PMID- 2245372 TI - Routine sheep and goat procedures. AB - Techniques involved in handling, restraint, sampling, identification, teat examination, and condition scoring are described. Procedures involved in foot trimming, docking, castrating, dosing, dehorning, descenting, dewattling, and giving injections are discussed. Care of the newborn is described. PMID- 2245373 TI - Anesthesia techniques in sheep and goats. AB - A variety of techniques can be used to anesthetize and restrain sheep and goats safely and humanely both in the clinic and in the field. The use of inhalational, injectable, and local anesthetic agents is discussed. Nontraditional agents (opioids and alpha-2 adrenergic agonists) for epidural analgesia also are reviewed because of their promising clinical application. PMID- 2245374 TI - Genetic diseases of sheep and goats. AB - Congenital malformations and inherited disorders constitute a substantial proportion of the afflictions seen in sheep and goats. Of these, malformations tend to be similar in both species, whereas the genetic diseases encountered to date, with the exception of a few, are different. Of the 28 genetic diseases of sheep and goats described in this review, 60% and 62.5%, respectively, are monogenic disorders. For a majority of the monogenic recessive disorders encountered in these species, the carrier state is not detectable at present, whereas in others, in which a biochemical lesion is known (dermatosparaxis, erythrocyte glutathione deficiency, globoid cell leukodystrophy and glycogen storage disease), the carrier state is detectable with the aid of enzyme and surface protein markers. The latter group and the dominant disorders (anury, cataract, glomerulonephritis, and lethal grey in sheep; gynecomastia and anotia microtia complex in goats) are easy to eliminate through selective breeding. The polygenic disorders (entropion, epidermolysis bullosa, hereditary chondrodysplasia, and muscular dystrophy of sheep, and udder problems in goats) are more difficult to eradicate, because the mutant genes responsible for these traits generally do not declare themselves until inbreeding brings together a critical concentration to create a health crisis in some, whereas others, which are only short of a few of these mutant genes, might go totally unaffected and therefore undetected. Chromosome defects of the structural nature (translocations) seen in sheep and goats generally create meiotic disturbances, which in a majority of cases lead to subfertility, whereas sex chromosome aneuploids are generally sterile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245375 TI - Unsolved problems of the goat industry. AB - A few of the challenges to successful goat farming have been mentioned. The veterinary practitioner is a pivotal specialist whose expertise and services could greatly improve productivity in all types of goat production, particularly because productivity appears to be limited mainly by disease. In my opinion, goat producers are, for the most part, trying to struggle on without us. This, I believe, is an unfortunate reflection of our failure to make them aware of how helpful we can be when invited to assist in making herd management decisions. PMID- 2245376 TI - Unsolved problems confronting the sheep industry. AB - To support a sheep production system, veterinary practitioners must integrate diagnosis, treatment, and prevention with management, nutrition, and economics. Scrapie, spider syndrome, prolapses, and parasitism are a few of the less dramatic but constant problems in sheep practice. Problems with drug availability and residues may be as difficult to solve as predation and economic problems. PMID- 2245377 TI - Ammonia-induced cell envelope injury in Escherichia coli and Enterobacter aerogenes. AB - Ammonia-induced cell envelope injury was examined in pure cultures of Escherichia coli and Enterobacter aerogenes. Cell injury, as determined by the ratio of colony-forming units on m-T7 agar to colony-forming units on m-Endo agar, increased with exposure to increasing concentrations of ammonia. Cell envelopes appeared to be the site of injury as indicated by increasing susceptibility to lysozyme with increasing ammonia concentration. Cells exposed to ammonia also exhibited more cellular leakage than control cells. Leakage from cells exposed to ammonia included proteins, and all leaked substances increased in concentration as ammonia concentrations increased. The concentration of 2-keto-3-deoxyoctonate (KDO) in the outer membrane of E. coli increased with ammonia exposure, while KDO concentration in the outer membrane of E. aerogenes decreased. The results suggest that exposure of E. coli cells to high concentrations of ammonia disrupts the outer membrane and lipopolysaccharide-associated proteins, while E. aerogenes cells are affected through the disruption of bonds between KDO and the outer membrane. PMID- 2245378 TI - Improved detection of acid mine water stressed coliform bacteria on media containing catalase and sodium pyruvate. AB - Pure culture suspensions of two strains of exponential and stationary phase Escherichia coli exhibited significant reductions in catalase activity following exposure to acid mine water (AMW). The exogenous addition of catalase (500-2000 U) or sodium pyruvate (0.05-5%) to a nonselective recovery medium resulted in enhanced detection (12- to 465-fold) of AMW-stressed E. coli as compared with recovery on the medium lacking these supplements, whereas addition of 3,3' thiodipropionic acid failed to improve recovery. Additional in vitro experiments utilizing selective M-FC, mT7, and M-Endo media containing 1000 U catalase or 1.0% pyruvate similarly resulted in improved detection of AMW-stressed cells, with the exception of M-Endo containing pyruvate. Appropriately modified media were then used to analyze an AMW-impacted stream by the membrane filtration technique. Addition of catalase, pyruvate, or a combination of both significantly improved recovery of fecal and total coliforms without promoting growth of noncoliforms. Supplementation of plate count agar with pyruvate and (or) catalase enhanced detection of total heterotrophs. These findings suggest that addition of catalase or pyruvate to standard recovery media may improve detection of coliform and total heterotrophic bacteria in AMW-impacted waters. PMID- 2245379 TI - Survival and inoculum potential of conidia and chlamydospores of Fusarium oxysporum f.sp. lini in soil. AB - The kinetics of survival and inoculum potential of Fusarium oxysporum f.sp. lini were studied in soil. Two types of inoculum were compared: microconidia freshly harvested from a laboratory-grown culture and microchlamydospores produced in sterilized soil. Introduced at the same inoculum densities into a natural soil, the two types of inoculum showed similar behavior; the inoculum densities changed little with time, at least during 100 days. However, the two types of inoculum did differ in disease potential. A higher percentage of microchlamydospores than microconidia germinated in the rhizosphere of flax seedlings, and the heterotrophic fluorescein diacetate hydrolysing activity of the microchlamydospores was 100 times higher than that of microconidia. Moreover, the microchlamydospores produced more disease on flax than the microconidia even at a much lower inoculum density. PMID- 2245380 TI - Bactericidal activity of magainin 2: use of lipopolysaccharide mutants. AB - Salmonella typhimurium and a series of rough lipopolysaccharide mutants derived from it were used as target bacteria to examine the antimicrobial capacity of magainin 2. Magainin 2 demonstrated a dose-related bactericidal activity against the smooth parent strain and the series of lipopolysaccharide mutants. The lipopolysaccharide mutant series showed an ordered increase in sensitivity to the magainin 2 as the depth of the rough lesion in the lipopolysaccharide increased. PMID- 2245381 TI - Esterase activity of pure cultures of rumen bacteria as expressed by the hydrolysis of p-nitrophenylpalmitate. AB - Seventy-four strains of rumen bacteria comprising 20 genera were tested for the ability to hydrolyze p-nitrophenylpalmitate (PNPP-C16). This ability was detectable in all cultures tested, but the level of activity was quite variable. Known lipolytic strains of these bacteria showed generally low levels of activity in this assay, which suggests that the hydrolysis of this artificial substrate indicates a general esterase activity and not a lipase activity, as reported in the literature. The highest activity was found to occur in strains known to be feed-particle-associated digesters of starch, pectin and cellulose. In fractionated rumen contents, p-nitrophenylpalmitase activity was largely associated with feed particles. Although the in vivo role of the enzymes that hydrolyze PNPP-C16 remains obscure, it appears that they are primarily of microbial origin, and may be important in hydrolyzing ester bond-containing compounds from plant material. PMID- 2245382 TI - Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway. AB - A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit. PMID- 2245383 TI - Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin's disease. A Southwest Oncology Group study. AB - The authors reviewed the records of 139 patients who had laparotomy plus computed tomography (CT) and/or lymphangiograms (LAG) as part of a their staging workup for Hodgkin's disease, in accordance with Southwest Oncology Group (SWOG) protocol 7808. They evaluated the relative ability of CT and LAG to detect disease in the abdomen. Two regions of the abdomen were designated, the upper and the lower, to further examine the capabilities of CT and LAG in the lower abdomen and CT in the upper abdomen. A LAG was more sensitive (P less than 0.05) than CT in detecting positive lower abdominal nodes. In the upper abdomen, CT scan had low sensitivity for detecting positive nodes, liver, or spleen. This study suggests that LAG of the lower abdomen provided more information than CT, and therefore should not be abandoned as a valid method for detecting nodal disease. PMID- 2245384 TI - Piroxicam decreases postirradiation colonic neoplasia in the rat. AB - This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. PMID- 2245385 TI - Diffuse sclerosing variant of papillary carcinoma of the thyroid. Clinical importance, surgical treatment, and follow-up study. AB - A diffuse sclerosing variant is not very rare among papillary carcinomas of the thyroid when the patients are female and younger than 30 years of age. The variant is characterized by diffuse involvement of one or both thyroid lobes, with dense sclerosis, patchy lymphocytic infiltration, and abundant psammoma bodies. Controversy still exists concerning its prognosis. We reviewed our experience with 14 patients treated between 1958 and 1988. All patients were young females, their age being from 10 to 28 years with a mean of 19.6. Hashimoto's thyroiditis had been suspected in nine patients before they came to our clinic. Nowadays the diagnosis of this cancer is possible when we have this entity in mind and detect abundant psammoma bodies either by ultrasonography or by soft-tissue roentgenography of the neck. Total thyroidectomy with modified neck dissection was carried out in eight patients, subtotal thyroidectomy with neck dissection in five, and lobectomy with neck dissection in one. All of them are alive and well without distant metastasis at a mean follow-up of 16 years. Because most of the patients with this variant of papillary carcinoma are young women and the prognosis is favorable, a complete resection without causing later recurrence, but also cosmetic and complication-free surgery, should be considered. PMID- 2245386 TI - Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes? AB - The effect of internal mammary chain treatment on each type of malignant death related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer. PMID- 2245387 TI - Superficial esophageal carcinoma. Surgical treatment and the results. AB - We report 92 patients treated with esophagectomy for superficial esophageal carcinoma (SEC; 9.1% of all resected esophageal cancers at our institution). The operative mortality rate was 5.4%. In 24 cases, cancer invasion was limited to the mucosa, and in 68 to the submucosa. Twenty-three patients in the former group had no lymph node involvement, whereas 24 patients (35.3%) of the latter group had lymph node metastases. The 5-year survival rate after surgery for patients with SEC limited to the mucosa was 83.5%, which was significantly better than that for carcinoma invading the submucosa (54.9%). No recurrent disease occurred in patients with lesions limited to the mucosa. In conclusion, an esophagectomy with wide lymphadenectomy is necessary to provide a better prognosis for SEC invading the submucosa, whereas a less extensive treatment may be considered for SEC limited to the mucosa. PMID- 2245388 TI - Lack of relationship between perioperative blood transfusion and survival time after curative resection for gastric cancer. AB - To better comprehend the relationship between perioperative blood transfusion and survival time after curative gastrectomy for advanced gastric cancer, the authors reviewed retrospectively data on 568 patients treated in their clinics from 1965 to 1983. Of these 568, 195 (34.3%) required no blood transfusion and 373 (65.7%) required transfusions within the perioperative period. Univariate analysis indicated that the survival time of the transfusion recipients was significantly less than that of the patients who had no transfusions (P less than 0.01). In subgroups of the authors' patients stratified to adjust for stage of disease, there was, however, no significant difference between the survival rates. Subsequently, multivariate analysis, using the Cox regression analysis, which adjusted for sex, age, and other covariates, indicated that perioperative blood transfusion was not a useful factor for predicting survival time. Multivariate analysis suggested that tumor size (P less than 0.01), degree of invasion into the gastric wall (P less than 0.01) and status of lymph node metastasis (P less than 0.01) were the most important covariates after curative gastrectomy for advanced gastric cancer. The authors' findings revealed the lack of any relationship between perioperative blood transfusion and survival time of patients who underwent curative resection for advanced gastric cancer. PMID- 2245389 TI - Transrectal ultrasonography of rectal carcinoma. AB - Preoperative transrectal ultrasonographic staging of 38 patients with known adenocarcinoma of the rectum was performed. Six of these patients had preoperative radiation therapy. Of the 32 without radiation therapy, transrectal ultrasonography (TRUS) correctly staged disease limited to the rectum in 90% (18 of 20) and transmural extension in 50% (6 of 12), for a sensitivity for evaluating transmural extension of 50%, specificity of 90%, positive predictive value of 75%, and a negative predictive value of 25%. Nineteen patients had positive nodes. The sensitivity and specificity of detecting nodal metastases by TRUS were 63% and 85%. The positive and negative predictive values were 86% and 61%, respectively. TRUS was slightly superior to digital rectal examination in staging patients because of its superior ability to detect adenopathy. Adjacent organ involvement was correctly evaluated in five of six patients; peritumoral fibrosis was misinterpreted as tumor extension into uterus and ovary in one woman. Tumor shrinkage in all patients undergoing radiation therapy was identified, but fibrosis and edema made staging by TRUS unreliable in those patients. PMID- 2245390 TI - Transfusion-induced graft-versus-host disease in patients with malignant lymphoma. A case report and review of the literature. AB - A case of transfusion-induced graft-versus-host disease (GVHD) occurring in a 31 year-old female with Hodgkin's disease in complete remission is reported. Clinical features are similar to 19 other reported cases of transfusion-induced GVHD associated with malignant lymphoma. The lack of relationship with underlying histology or disease stage and the nearly uniformly fatal outcome underscores the importance of prophylactic irradiation of blood products given to patients with malignant lymphoma undergoing therapy. PMID- 2245391 TI - The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. AB - MaxEPA (MA), a fish oil high in omega-3 fatty acids, was combined with various levels of corn oil (CO), rich in omega-6 fatty acids, and fed to female CF1 mice. The three fish oil blends with CO and the two CO levels of the diets studied were as follows: 16.0% CO + 4.4% MA (Diet 1); 10.2% CO + 10.2% MA (Diet 2); 4.4% CO + 16.0% MA (Diet 3); 20.4% CO (Diet 4); and 4.4% CO (Diet 5). The diets were provided 2 weeks before weekly subcutaneous injection of saline or azoxymethanol (AOM). Studies of epithelial cell proliferation and the incidence of focal areas of dysplasia (FAD) involved six weekly AOM injections. One week after the last AOM injection and 1 hour before killing, mice were injected with tritiated thymidine (3HTdR). No differences in any proliferative parameters were found among the five groups of saline-treated mice. Among the AOM-treated animals, those fed Diet 3 showed significantly fewer cells per crypt and significantly fewer labeled cells/gland than CO Diets 4 and 5. Additionally, the distribution of S-phase cells in crypts of AOM-treated mice fed Diet 3 most closely resembled that of the saline controls. The greatest alteration in the distribution of proliferative cells was observed in the high-CO diet (Diet 4) and the lowest MA level (Diet 1). Mice fed Diets 2 and 3 had significantly fewer FAD/500 microns of distal colonic serial sections than those fed the high CO diet (Diet 4). Mice involved in chronic tumor incidence studies received only three weekly injections of the same dose of AOM. Regardless of diet, approximately 88% of all tumors arose in the distal colon. A significantly larger tumor-bearing population was observed in both the high-CO Diet 4 and the lowest MaxEPA (MA) diet (Diet 1) compared with the incidence in MA Diets 2 and 3 and the low-CO Diet 5. A diet with a ratio of omega-6 to omega-3 fatty acids of approximately 1.0 apparently prevented the development of an adenoma-type proliferative pattern thereby reducing FAD numbers and subsequent tumor incidence. PMID- 2245392 TI - Aneuploidy in pancreatic insulinomas does not predict malignancy. AB - Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas. PMID- 2245393 TI - Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. Clinical, histopathologic, and immunohistochemical analyses. AB - An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which usually shows the same phenotype as CTCL, i.e., a helper/inducer T-cell phenotype (CD4+CD8-), and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. In this study, we demonstrated differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i.e., CD4-CD8-, CD4+CD8-, and CD4-CD8+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL 2R), CD71 (OKT9), HLA-DR, and HLA-DQ was higher in the skin-infiltrating ATL cells than in CTCL cells. Expression of CD29 (4B4) was high, and that of CD45RA (2H4) was low in both the skin-infiltrating ATL and CTCL cells compared with the peripheral blood and lymph node ATL cells. Expression of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotypic difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL is a disease distinct from CTCL. PMID- 2245394 TI - von Willebrand factor in head and neck cancer. AB - Laboratory abnormalities in blood coagulation factors are common in patients with cancer but the significance is unknown. Twenty-eight patients with head and neck cancer were studied at the time of diagnosis. Twenty-five were advanced-stage (III or IV) patients. Levels of clotting factors, antithrombin III, and plasminogen were normal. Levels of von Willebrand factor (vWF), both antigenic and functional (ristocetin cofactor), were elevated. This group of patients were followed for a minimum of 41 months (median, 48 months). Fifteen patients died within the follow-up period. von Willebrand factor levels were significantly higher in these 15 than the 13 survivors. Extreme elevation of ristocetin cofactor (greater than 300 U/dl) was seen in six of the 15 patients who died and in none of the survivors. Plasma vWF is elevated in head and neck cancer and the level measured at the time of diagnosis may have prognostic and potentially therapeutic implications. PMID- 2245395 TI - Tumor factors predicting for prognosis in metastatic breast cancer. The presence of P24 predicts for response to treatment and duration of survival. AB - Fifty-one patients with metastatic breast cancer were investigated to determine tumor parameters with prognostic significance. Investigations included determinations of P24 content by immunocytochemical means using a monoclonal antibody to P24 protein; immunocytochemical analysis of estrogen and progesterone receptors; ploidy analysis by flow cytometry, and histologic grading. There were significant correlations between the presence of P24 and estrogen receptor, between histologic grade and P24 expression, and between estrogen and progesterone receptors. Of the tumor factors investigated only P24 protein was, however, of prognostic significance. Patients with P24-positive tumors had a significantly higher rate of response to treatment as well as more prolonged duration of response and duration of survival from diagnosis of metastatic disease. None of the other variables investigated were significantly predictive of outcome. P24 protein may be a useful predictor of prognosis in metastatic breast cancer. PMID- 2245396 TI - Serum concentrations of CA 125 and aminoterminal propeptide of type III procollagen (PIIINP) in patients with endometrial carcinoma. AB - Serum CA 125 (a marker of coelomic epithelial cells) and aminoterminal propeptide of type III procollagen (PIIINP; an indicator of collagen metabolism) concentrations were measured in 148 patients with endometrial carcinoma. An initial serum concentration of CA 125 was pathologic in 17% of the patients, the frequency of abnormal values being higher (P = 0.0001) in advanced (63%) than in early disease (10%). The serum PIIINP concentration was increased in 35% of the patients and more often (P less than 0.05) so in advanced (63%) than in early disease (31%). Among all the patients, at least one of the tumor markers was increased in 43% of the cases. In early disease 12 of 108 patients contracted recurrent cancer. The accuracy of the pathologic CA 125 (9%) and PIIINP (18%) concentrations in their prediction was poor. In the total material, pathologic CA 125 and PIIINP concentrations appeared simultaneously in 11 patients, of whom eight had poor prognoses. In monitoring of treatment response of 24 patients, regression was accompanied by normal or decreasing CA 125 and PIIINP values. The persistence of pathologic CA 125 and/or PIIINP concentration predicted relapse of the malignancy. In progressive disease, CA 125 and PIIINP concentrations together or separately remained at a pathologic level or increased continuously. In clinically stable endometrial carcinoma, CA 125 gave false-negative results in 71% of the determinations and PIIINP only in 12%. The current results suggest the use of CA 125 and PIIINP, simultaneously, in monitoring the clinical course of advanced endometrial carcinoma. PMID- 2245397 TI - Angiocentric immunoproliferative lesion/T-cell non-Hodgkin's lymphoma and the acquired immune deficiency syndrome: a case report and review of the literature. AB - The lesions known as lymphocytic vasculitis, polymorphic reticulosis (midline malignant reticulosis, lethal midline granuloma), lymphomatoid granulomatosis, and angiocentric lymphoma form what have been collectively termed the angiocentric immunoproliferative lesions (AIL). Because of recent reports demonstrating clonal rearrangements of the T-cell receptor in these lesions, the AIL are now thought to represent a continuous spectrum of post-thymic T-cell non Hodgkin's lymphoma (NHL). NHL associated with the acquired immune deficiency syndrome (AIDS) represents intermediate or high-grade B-cell malignancies in HIV infected patients that may be etiologically related to the Epstein-Barr virus (EBV). There have been reports of EBV-associated T-cell NHL, AIL, and large granular lymphocyte (LGL) proliferations, as well as HIV-associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. We describe a case of polymorphic reticulosis (lethal midline granuloma) arising in an HIV-infected individual, who later progressed to AIDS, and review the literature on HIV-associated and EBV associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. The etiology of this AIL/T-cell NHL, especially in relation to EBV and HIV, is discussed. PMID- 2245398 TI - Splenic rupture in a human immunodeficiency virus-infected patient with primary splenic lymphoma. AB - Splenic rupture presenting as primary malignant lymphoma of the spleen is a rare event. We report such an occurrence in a young man who had a primary B-cell immunoblastic lymphoma of the spleen and was found to be HIV-positive. We suggest that serologic tests for HIV should be performed in unusual cases of malignant lymphoma. PMID- 2245399 TI - Disseminated strongyloidiasis with central nervous system involvement diagnosed antemortem in a patient with acquired immunodeficiency syndrome and Burkitts lymphoma. AB - A 45-year-old man presented with central nervous system involvement as the initial manifestation of disseminated infection with Strongyloides stercoralis. Several concurrent clinical factors contributed to this event, all related to the patient's immunosuppression, including high-grade lymphoma, corticosteroid therapy, and acquired immunodeficiency syndrome. This is only the third case of CNS involvement in disseminated strongyloidiasis diagnosed antemortem. PMID- 2245400 TI - Abnormal vitamin B6 status in childhood leukemia. AB - Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status. PMID- 2245401 TI - Melanoma and soft tissue sarcoma in seven patients. AB - Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between melanoma and sarcoma, the nature of which remains unknown. PMID- 2245402 TI - The epidemiology of cancer among Hispanic women. The experience in Florida. AB - To explore cancer incidence among Hispanic women living in Dade County, Florida, data were analyzed from the statewide cancer registry. For all but three sites, Hispanics had lower rates of the 15 most prevalent cancers than non-Hispanics. However, higher rates of cancer among Hispanics were noted for cancers of the gallbladder, liver, and heart and soft tissue. Subgroups of women had significantly higher rates of cervical cancer and thyroid cancer. Lower rates among Hispanics were observed for cancers of the esophagus, vagina, breast, colon, buccal cavity and pharynx, and malignant melanoma. These data suggest that most cancer sites traditionally higher among US Latino women were not higher among Dade Hispanics, and that sites more common among non-Hispanics have not yet shown an increased incidence among Hispanic women in Dade County. PMID- 2245403 TI - Increasing incidence of cecal and sigmoid carcinoma. Data from the Connecticut Tumor Registry. AB - We have studied both the distribution and incidence of colorectal cancer using The Connecticut Tumor Registry, the oldest tumor registry in the United States. During the time period 1973 to 1985, left-sided colon cancers accounted for 63% of the cancers, right-sided cancers 33%, and cancers with unspecified sites 4%. Indeed, this pattern of distribution has remained constant for 25 years. For the period 1935 to 1985, we calculated the sex-specific, age-adjusted (normalized to the 1970 U.S. Census) incidence. Age-adjusted incidence of rectal cancer has remained stable for 50 years: for men, 22.8 cases/100,000/year, and for women, 13.9 cases/100,000/year. During these 50 years, the age-adjusted incidence of cecal carcinoma for men has increased from 3.6 to 16.7 cases/100,000/year, while for women, it has increased from 4.9 to 14.2 cases/100,000/year. Sigmoid carcinoma for men has increased from 8.8 to 18.7 cases/100,000/year, and for women, it has increased from 7.7 to 12.8 cases/100,000/year. The incidence of colon cancer at each site has been and continues to be increasing at a constant rate. Age-adjusted incidence for all colorectal cancers has increased from 35.2 to 70.2 cases/100,000/year for men and from 32.1 to 49.2 cases/100,000/year for women. Thus, distribution of colorectal cancers by site in Connecticut has remained stable for 25 years. More importantly, however, the age-adjusted incidence of colon cancer has continued to increase for 50 years, whereas that of rectal cancer has remained relatively stable. PMID- 2245404 TI - Effects of retinoic acid on the in vivo growth of human neuroblastoma cells. AB - We have investigated the effects of retinoic acid (RA) on the development and growth in nude mice of tumors derived from the human neuroblastoma cell line LA-N 5. When cells were treated with 4 x 10(-6) M RA in vitro there was a marked reduction in the number of mice developing tumors when compared to solvent treated controls. In vivo treatment with RA reduced tumor formation when the retinoid was given for 5 days before tumor injection and continued for 14 days thereafter. In established tumors, RA inhibited progressive tumor growth. There was no demonstrable effect of RA in vivo on the morphologic phenotype of the tumor cells when these regimens were used. We conclude that oral retinoid administration may prove useful in inhibiting or arresting the growth of neuroblastoma, particularly when there is a small initial tumor burden. PMID- 2245405 TI - Scanning tunneling microscopy imaging of the tumour associated antigenic 20 amino acid human polymorphic epithelial mucin core peptide fragment. AB - Human polymorphic epithelial mucins (PEM) are high molecular weight glycoproteins that are associated with breast cancer. Recent structural studies have identified that the protein core of PEM contains a 20 amino acid tandem repeat that has elements of secondary structure which coincide with the epitopes for a number of tumour reactive antibodies. In our continuing structural studies we have now investigated the use of the scanning tunneling microscope (STM) to directly image the conformation of the twenty amino acid PEM core peptide. High resolution STM images reveal that the peptide has an overall topography similar to that predicted by molecular modelling. The images identify directly that the free peptide is conformationally non-restricted and can adopt a number of discrete conformations in the solid state. PMID- 2245406 TI - Activity of various amphiphilic agents in reversing multidrug resistance of L 1210 cells. AB - Several compounds (bamipine, chlorphenoxamine, estracyt, hycanthone, quinidine, quinine, tamoxifen, trifluoperazine and verapamil) have a common basic structure with the following features: lipophilic aromatic ring system; linked chain hydrophilic N-alkyl group. They are used medically for varying diseases. Their activity in reversing multidrug-resistance (MDR) with other compounds (diethylstilbestrol, beta-estradiol, methylbiguanide, methylpiperazine, testosterone) lacking one of these chemical features is compared. The in vitro test system we used was the nucleoside incorporation assay using parental L 1210 ascites tumor cells and a doxorubicin resistant subline, which expresses the MDR phenotype. The substances lacking one of these features were not effective in reversing the MDR whereas all other tested substances demonstrated modulating potential in the MDR resistant L 1210 cells. PMID- 2245407 TI - Inhibition of rat hepatic glutathione S-transferase placental form positive foci development by concomitant administration of antioxidants to carcinogen-treated rats. AB - Inhibition potential of concomitant butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), catechol or sodium ascorbate (Na-AsA) administration on development of diethylnitrosamine (DEN) initiated glutathione S-transferase placental form (GST-P) positive foci in rat liver under the influence of 2 acetylaminofluorene (2-AAF) or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) plus partial hepatectomy (PH) was investigated. Whereas BHA, BHT and catechol exerted marked inhibitory effects, Na-AsA lacked any modifying potential. The compounds that demonstrated inhibition also induced GST-P in the hepatic periportal areas, suggesting that development of GST-P positive foci is negatively influenced by extra-focal increase in this enzyme form observed with BHA, BHT or catechol. PMID- 2245408 TI - Neoplastic transformation and DNA damage of mouse mammary epithelial cells by N methyl-N'-nitrosourea in organ culture. AB - An appropriate in vitro system was used to study the effect of a direct-acting carcinogen on the transformation of mammary epithelial cells in the organ culture of the whole mammary gland in vitro. Studies were done to determine the ability of N-methyl-N'-nitrosourea (MNU) to transform the mammary cells in organ culture. Mouse mammary glands were treated with single or multiple doses of MNU during various periods of the culture. To assay for neoplastic transformation potential of MNU on mammary cells, mammary glands were dissociated and the cells were injected into the parenchyma-free inguinal mammary fat pad of syngeneic virgin female host mice. Palpable tumors were observed in injected glands of 23% of the mice after 3-4 months and an additional 31% showed serially transplantable hyperplastic alveolar nodules (HANs). Histopathologic examination of the tissues showed that the tumors were mammary adenocarcinoma. All tumors and hyperplasias were secondarily transplanted into syngeneic animals, resulting in tumors and hyperplasias of similar histopathology. In addition, DNA damage of the epithelial cells in organ culture caused by MNU was also measurable using the new nick translation assay. The most extensive DNA damage occurred when the glands were treated on day 4 and day 5 of the mammogenic culture period. These results demonstrate that the mouse mammary epithelial cells are susceptible to the carcinogenic action of the direct-acting carcinogen MNU and that the whole mammary gland-culture system offers an appropriate in vitro model for studying the mechanism of carcinogenesis induced by MNU. PMID- 2245409 TI - Thymidine enhancement of carboplatin cytotoxicity: in vivo studies in normal B6D2 F1 mice. AB - Our laboratory has previously demonstrated that 4-24-h thymidine exposures (50 1000 micrograms/ml) will enhance carboplatin cytotoxicity 2-3.3-fold in vitro. In order to show that these results are clinically applicable, we performed 24-h thymidine infusions with and without carboplatin in B6D2 F1 mice. The mice were evaluated for myelosuppression, weight loss and development of diarrhea. Results obtained demonstrated that thymidine did not enhance systemic carboplatin toxicity. The clinical relevance of these results is discussed. PMID- 2245410 TI - Effects of naturally occurring antioxidants on combined 1,2-dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis in F344 male rats. AB - The effects of treatment with naturally occurring antioxidants, selenium, beta carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2 dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions. PMID- 2245411 TI - Liver genotoxic activity of an epoxide derivative of the hepatocarcinogenic beta blocker DL-ZAMI 1305. AB - A single administration of the sex-dependent hepatocarcinogenic beta-blocker DL-1 (2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) induces dose-dependent liver DNA damage, as evaluated by alkaline sucrose gradient analysis, in female but not in male Fisher 344 rats. A single administration of the direct mutagenic epoxide-derivative of DL-ZAMI 1305 3-methyl-2-nitro-1-(2,3 epoxypropoxy)-benzene induces dose-dependent DNA damage in the liver of animals of both sexes. However, also in this case, the genotoxic activity of the compound appears to be significantly higher in female than in male rats. A DNA-damaging capacity similar in the two sexes is instead exerted by DL-ZAMI 1305-unrelated direct mutagens, like N-methyl-N-nitrosourea (MNU) and methyl-methanesulfonate (MMS). The data confirm the sex-dependent susceptibility of rat liver to the genotoxic activity of DL-ZAMI 1305-related molecules, also in the absence of an absolute requirement for a metabolic activation of the compound. PMID- 2245412 TI - Synergistic effect of mammary tumors on hexachlorobenzene-induced porphyria in rats. AB - The response of animals bearing N-nitroso-N-methylurea (NMU)-induced mammary tumors to the porphyrinogenic action of hexachlorobenzene (HCB) was studied. delta-Aminolevulinic acid (ALA), porphobilinogen and porphyrins in urine, ALA synthase and porphyrinogen carboxylase activities and porphyrin content in liver and tumor were measured. The results obtained indicate that the metabolic heme pathway operates in mammary tumors but tumor response to HCB treatment could not be detected. HCB administration produced an earlier and greater hepatic porphyria in tumor-bearing rats than in healthy rats suggesting that the presence of tumors exacerbates the action of HCB. PMID- 2245413 TI - The structural basis for the mutagenicity of aristolochic acid. AB - Molecular orbital calculations with aristolochic acid I (AAI) and the model compounds 8-nitro-1-naphthoic acid (1,8NNA) and 3-nitro-2-naphthoic acid (2,3NNA) confirm a similar conformation of the nitro and carboxyl groups in these molecules. The ortho isomer 2,3NNA is not mutagenic in the Salmonella strains TA 100 or TA 1537, but the peri-substituted 1,8NNA shows mutagenic activity similar to AAI in TA 100, although it is only weakly active in TA 1537. We propose a mechanism of activation via a cyclic nitrenium ion with an aristolactam structure which is possible only in peri-substituted nitro carboxylic acids. PMID- 2245414 TI - Inhibitory effects of fucoxanthin, a natural carotenoid, on N-myc expression and cell cycle progression in human malignant tumor cells. AB - Fucoxanthin, a natural carotenoid prepared from brown algae, inhibited the growth of GOTO cells, a human neuroblastoma cell line. Fucoxanthin at 10 micrograms/ml reduced the growth rate of GOTO cells to 38% of the control at day 3 after drug treatment. Flowcytometric analysis revealed that fucoxanthin caused the arrest in the G0-G1 phase of cell cycle. Expression of N-myc gene was proved to be decreased by fucoxanthin as early as 4 h after treatment at 10 micrograms/ml and that may be important for the mechanism of anti-proliferative action of the carotenoid. PMID- 2245415 TI - The psychological effects of support groups on individuals infected by the AIDS virus. AB - Support groups have been suggested as the best way to help individuals with AIDS to cope. The purpose of this research was to determine whether participation in an AIDS support group would significantly decrease the level of anxiety and hopelessness in individuals with AIDS. Subjects in the study were volunteers from three support groups at AID Atlanta. The groups included (a) 11 men with classic AIDS, (b) 6 men with AIDS or AIDS-related complex (ARC), and (c) 5 minority women with AIDS or ARC. A demographic form and two questionnaires that dealt with anxiety and hopelessness were administered as a pretest and posttest. The results of the demographic data analyses showed that groups 1 and 2 were similar, whereas group 3 was dissimilar to both groups 1 and 2. Findings further indicate that group 3 had a significantly greater decrease in hopelessness scores after participating in the AIDS support group. This group also had a greater decrease in anxiety scores but not at a significant level. In conclusion, the findings of this study suggest that participation in an AIDS support group does decrease the level of anxiety and hopelessness. Therefore, the impact on society is to educate individuals with AIDS and professional persons who work with this population to be aware of the psychological benefits that support groups do provide these individuals. PMID- 2245416 TI - Loneliness and coping among tertiary-level adult cancer patients in the home. AB - This exploratory study measured the degree of loneliness experienced by adult cancer patients. All were in the initial phases of the illness, that is, currently receiving treatment consisting of either chemotherapy or radiation therapy on an outpatient basis and/or recuperating from surgery in the home setting. All were within 100 days of initial diagnosis of cancer. The UCLA Loneliness Scale by Peplau was used in measuring loneliness. In addition, the coping methods of this same group of patients were examined using the Jalowiec Coping Scale to determine predominant methods of coping with the situational crisis imposed by cancer diagnosis and treatment. The instruments were administered in the home or in an outpatient setting and patients were accessed through cancer treatment centers and from oncologists in the southern Illinois area. The study was conducted to determine the prevalence of loneliness, to identify predominant coping methods, and to discern the relationship, if any, between coping methods employed and the degree of loneliness reported by the adult cancer patients. The conceptual framework chosen for the study was taken from the work of Lazarus and Jalowiec with regard to coping; the work of Peplau, Russell, and Cutrone on loneliness formed the conceptual basis for the portion of the study regarding that dimension. A total of 41 cancer patients were surveyed- 21 were male and 20 were female. The median age was 60 years, and the mean educational level was 10.5 years. There were significant differences found between loneliness scores by age categories and by marital status, as well as a relationship between membership in organizations and loneliness scores. There were significant relationships found between coping methods (confrontive, emotive, palliative) employed and the degree of loneliness experienced by these cancer patients. Coping methods were also ranked by frequency of use, and interesting patterns emerged--especially noteworthy were group findings regarding most- versus least-preferred methods. Based on the sample results of this small study, a profile of vulnerability emerges for the adult cancer patient within 100 days of diagnosis. Nursing interventions aimed at alleviating loneliness and facilitating positive coping are indicated, as well as the need for continued study with an expanded population. PMID- 2245417 TI - A 14-year investigation into the workload of oncology nurses in The Netherlands Cancer Institute. AB - In the Netherlands Cancer Institute, the daily workload of nurses has been measured since 1976. Each day the head nurse ranks the patients into one of the seven categories of care requirements. It can be inferred from the data that the percentage of patients who need intensive nursing care has doubled from 30% in 1976 to more than 60% in 1989. The increase in the nursing staff has only partially kept abreast of the increase in the workload. In addition to this simple technique, a more refined "factor evaluation system" has been developed. On the basis of this method, a more detailed check can be made as to what connection there is between the characteristics of the patient, the particular disease and treatment on the one hand, and the nursing workload on the other. Because of this it is possible to assess and to predict the consequences for nursing care when a new therapy is introduced. The correlation between both assessment methods is good: 0.72. A plea is made to use both methods of assessment in conjunction: the simple method for assessing the daily workload, and the refined and thus more laborious method to analyze the factors responsible for changes in the workload. In view of the rapid dissemination of new oncological therapies, it is essential that international consensus be reached with regard to a method for measuring the workload of nurses. In this way the consequences of these new therapies for the workload of nurses might be known more rapidly and proper measures could be taken. PMID- 2245418 TI - Effects of coping style and relaxation on cancer chemotherapy side effects and emotional responses. AB - This study was designed to determine (a) the relationship of coping style to cancer chemotherapy side effects and (b) whether coping style moderated the impact of a relaxation intervention on anxiety, depression, and nausea associated with chemotherapy. Forty-eight cancer patients were assigned randomly to receive either progressive muscle relaxation training before chemotherapy (experimental group) or standard care (control group). Spearman correlations indicated that a "blunting" or distraction-oriented coping style was associated with less anticipatory anxiety, less depression, and less nausea during and after chemotherapy. Spearman correlations also indicated that a "monitoring" or information-gathering coping style was associated with more anticipatory anxiety, and more nausea before and during chemotherapy. Although there was a significant effect of the relaxation intervention on posttreatment nausea, there were no other between-group differences. The results did suggest, however, that relaxation was effective in reducing anticipatory anxiety among "blunters," but not "monitors," perhaps because relaxation is a distraction strategy and therefore is consistent with a blunting coping style. The effects of coping and relaxation on pretreatment anxiety may have important implications, because anxiety is a key factor in classic conditioning models of anticipatory nausea and vomiting. PMID- 2245419 TI - Application of Orem's conceptual framework to patients with hypercalcemia related to breast cancer. AB - Breast cancer is the most common malignancy in women in the United States. Although the disease itself may be chronic in nature, it may give rise to oncologic emergencies, such as hypercalcemia, superior vena cava syndrome, or spinal cord compression. If these emergencies are not prevented or treated promptly through early detection, premature death or disability may occur. Because it presents with general symptoms, hypercalcemia may be difficult to diagnose; however, early recognition and intervention may reverse the sequelae of this condition, and prevent recurrence. This article will focus on the pathophysiology, epidemiology, nursing assessment, and intervention in a case study of this oncologic emergency based on the Orem model. PMID- 2245420 TI - [Neuropeptide Y in the cardiovascular regulation]. PMID- 2245421 TI - [Cardiac involvement in HIV infection: a prospective, multicenter clinical and echocardiographic study]. AB - Cardiac abnormalities are frequently reported in patients with acquired immunodeficiency syndrome (AIDS). Much less is known about the true prevalence of cardiac involvement in patients with human immunodeficiency virus (HIV) infection. We prospectively examined 138 consecutive patients with HIV infection including 41 with AIDS, 49 with AIDS-related complex (ARC), 32 with chronic lymphoadenopathy syndrome (LAS) and 16 with asymptomatic HIV infection. Sixty-one patients had opportunistic infection. The prevalence of cardiac involvement progressively increased from patients with HIV infections or LAS (4%) to ARC (14%) to AIDS (37%). "Major" echocardiographic abnormalities (dilated cardiomyopathy and/or infective endocarditis and/or severe pericardial effusion) were identified in 3 patients (2%), "minor" abnormalities (mild pericardial effusion, hypokinesis of the interventricular septum, mild dilatation of the left ventricle in 21 (15%). Electrocardiographic abnormalities unassociated with echo abnormalities or clinical problems were seen in other 11 patients. End diastolic left ventricular dimension (normalized for body surface area) was higher among AIDS respect to pre-AIDS patients (30.1 +/- 7.1 vs 27.6 +/- 7.5; p less than 0.01) and among patients with respect to patients without opportunistic infections (29.5 +/- 6.5 vs 27.5 +/- 2.4; p less than 0.05). Left ventricular shortening fraction was lower in the subgroup with and absolute CD4 lymphocyte count less than 100/mm3 (31 +/- 7 vs 34 +/- 5; p less than 0.055). In conclusion, in a large, unselected group of patients with HIV infection, echocardiogram discloses cardiac abnormalities in 17% of the cases; their clinical relevance is generally low but in selected patients cardiac tamponade and/or dilated cardiomyopathy (secondary to viral myocarditis) may cause death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245422 TI - [Cardiovascular reactivity to isometric stress in patients with stable and borderline hypertension and in normotensive subjects. Effects of alpha sympatholytics and beta blocking agents]. AB - Aim of the study was to evaluate blood pressure (BP) and heart rate (HR) variability during isometric handgrip test (IHT) in 20 ambulant non-obese male adults affected by sustained hypertension (SH) WHO I and II, 20 borderline hypertensive (BH) and 20 normotensives (C) of comparable sex, age and BMI. SBP and DBP were assessed by "Random Zero" sphygmomanometer, HR by ECG registration. IHT was performed at 30% of maximal effort for 3 min. IHT was carried out: 1) after 7 days placebo, 2) after 7 days propranolol treatment (80 mg/day) and, following 10 days wash-out, 3) after 7 days prazosin treatment (0.5 mg/day). After placebo IHT caused increases of SBP, DBP and HR values insignificantly different in the 3 groups. After propranolol IHT induced significantly more elevated SBP and DBP increases in SH than in BH or in C. These increases were significantly more elevated in comparison with those observed, in advance, in the same group of SH subjects after placebo. After prazosin treatment SBP increase induced by IHT was, on the contrary, significantly more elevated in BH than in SH or in C. This increase is more significant in comparison with that observed in the same BH group after placebo treatment. As for DBP variations induced by IHT after alpha sympatholytic therapy we have observed that SH subjects show significantly lesser diastolic variations as compared with those obtained in BH or in C groups after this treatment. In conclusion, enhanced IHT induced SBP elevation after propranolol and dampened DBP reactivity after prazosin suggest an overriding alpha stimulation in SH subjects. SBP hyperreactivity induced by IHT after alpha sympatholytic treatment and DBP hyporeactivity after betablockers emphasize the role of beta stimulation in BH individuals. Inhibition of BP reactivity to IHT in C after prazosin suggest that this one is mediated by alpha adrenergic receptors. PMID- 2245423 TI - [Neurohumoral changes induced by hemofiltration in congestive heart failure: physiopathological inferences]. AB - Hemofiltration is a method suitable for rapid substraction of plasma water that generally allows reduction of circulating levels of norepinephrine. Using that non-pharmacological approach we investigated the mechanisms involved in the metabolism of the hormone as well as the hemodynamic correlates of a prompt and great fall of the sympathetic neurotransmitter in patients with chronic refractory congestive heart failure (CHF). In 23 patients with CHF, hemofiltration of 2983 +/- 1228 ml of plasma water (in 5 +/- 2 hours of treatment) increased urinary output by 606 +/- 415 ml in the day of the procedure as well as sodium excretion by 53 +/- 38 mEq/24 h; simultaneously, a mean fall in plasma norepinephrine concentration by 515 +/- 444 pg/ml was observed. These effects were prompt and persisted or even rose in the next 24 and 48 hours, not being related to changes in plasma renin activity, right atrial, wedge pulmonary artery and renal perfusion pressures and to the amount and duration of hemofiltration. Our data did not clarify the mechanism involved in the increase of the diuresis and for its coupling with the fall in plasma norepinephrine. Nevertheless, we found a strong and statistically significant correlation (r = 0.7; p less than 0.01) between percent changes from baseline values of norepinephrine and diuresis. It is therefore suggested that the same, still unknown, mechanism which increased urinary output also potentiated norepinephrine removal by the kidney: or that water reabsorption from extravascular spaces (triggered by hemofiltration and continued by increased diuresis) resulted in regression of organ congestion leading to an improved clearance of norepinephrine by different organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245424 TI - [Pseudoischemic T waves: a possible electrophysiologic mechanism]. AB - An electrophysiologic study has been performed in 7 patients with giant stable inversion of the T waves in the precordial ECG leads and without any organic heart disease. The study was particularly directed to evaluate the specific properties of the conductive system. The main results of the study point out the presence of absolute (prolonged HV interval, delay of ventricular activation time) or relative (RRP of the left bundle branch greater than RRP of the right one) conduction delays already in basic conditions or occurring after ajmaline (1 mg/Kg iv). Moreover, repolarization normalized during repetitive high rate atrial extrastimuli in the beats where ventricular activation time shortened and not during regular pacing. On the other hand, repolarization worsened whenever an impairment of infra or intrahisian conduction occurred. During His bundle pacing an inversion of the T waves preceded a left bundle branch conduction delay. The present data make us to hypothesize that, in these patients with pseudoischemia, a delay of activation of the initial vectors of the QRS in the left side, by amplifying the electrical gradient between the 2 ventricles, can be the underlying mechanism causing the repolarization abnormalities. PMID- 2245425 TI - [Differentiated circadian chrono-risk of acute myocardial infarct]. AB - In order to determine whether acute myocardial infarction (AMI) presents a circadian periodicity in its occurrence, the onset of AMI, evaluated by onset of clinical symptoms and pain, has been analysed in 520 patients with AMI. The definitive criteria of AMI were: typical chest pain, electrocardiographic findings, and plasma CPK-MB elevation. All cases of AMI were divided into subgroups according to sex (males = 369, females = 151), age (less than 60 years old = 254, more than 60 years old = 266), type of AMI (Q wave AMI = 407, non Q wave AMI = 113), previous pharmacological treatment (no treated = 373, treated = 147), history of arterial blood hypertension (normotensive = 403, hypertensive = 117). Cases of Q and non Q wave AMI were also subdivided according to treatment and hypertensive conditions. All AMI occurred outside hospital; silent AMI and reinfarctions were excluded by analyses. The data have been analysed by chronograms and by means of "single cosinor" method, both for total cases, and for each subgroup of AMI. The results show a diurnal variation in AMI occurrence regarding the whole group, with a peak from 4:00 am to noon and with a secondary small no-significant peak in the late evening, and the minimum in the afternoon. Rhythmometric analysis demonstrates a significant circadian rhythm (p less than 0.001) with acrophase at 7:52 am (from 6:08 am to 9:36 am). A statistically significant circadian rhythm is demonstrated in each subgroup, except in hypertensive patients. Acrophases of males and females, and of patients aged over or under 60 years do not differ from that of the whole group, and between them (p greater than 0.05). The peak of non Q wave AMI occurs at 4:44 am, while the peak of Q wave AMI at 10:08 am: this difference is significant (p less than 0.001). There is also a significant difference between the acrophases of AMI in the treated and untreated groups (p less than 0.01), as well as between normotensive and hypertensive subjects (p less than 0.001). The previous treatment seems able to anticipate the maximum occurrence of AMI in the whole group and in the group of Q wave AMI. These results are very similar to previous observations and confirm the greater morning occurrence of AMI. The present data are discussed in respect with the literature observations, and the possible pathophysiological mechanisms that contribute and conditionate the morning increase and the different peaks in subgroups of AMI patients are discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245426 TI - [Von Hippel syndrome with recurrent pheochromocytoma]. AB - A patient with Von Hippel disease is described. The Von Hippel syndrome is a genetic disease characterized by a retinal angiomatosis and multiple tumors (renal and pancreatic sites are common). The pheochromocytoma is-on the contrary very uncommon and the association with 2 pheochromocytomas has probably never been reported. In our case, a double pheochromocytoma (the first in 1973, the second in 1986) was present, in conjunction with a thyroid tumor and with an anomalous renal vein (circumaortic ring). The clinical picture was characterized by a severe hypertension and a fourth stage retinopathy. A correct diagnosis was established only 10 years after the clinical exordium. The thyroidectomy and the ablation of both the pheochromocytomas were necessary. PMID- 2245427 TI - [Primum vivere, simulque philosophari: a contribution to an intellectual theory of specialist medicine]. PMID- 2245428 TI - [Digitalis today: new strategies in the treatment of heart failure]. PMID- 2245429 TI - [Relationship between arrhythmia profile, left ventricular function and sudden death in the post-infarct period of patients resuscitated from heart arrest]. AB - In order to determine the relationship among ventricular arrhythmias, left ventricular dysfunction and sudden cardiac death (SCD), 75 consecutive patients with myocardial infarction, 38 of whom resuscitated from SCD, were studied retrospectively by 48 hour Holter electrocardiographic monitoring (ECGD), cardiac catheterization and radionuclide angiography (ACRD). The patients were divided in 3 groups, related to SCD occurrence and to the interval between acute myocardial infarction (AMI) and SCD: Group I (37 patients-control group) no cardiac arrest occurred; Group II (26 patients) resuscitated less than or equal to 48 hours after AMI; Group III (12 patients) resuscitated 6-12 weeks after AMI. ECGDs were recorded with an average of 2 (ECGD 1), 16 (ECGD 2) and 36 months (ECGD 3) after AMI. In ECGD 1, there were no differences in the frequency and complexity of ventricular arrhythmias among the 3 groups, whereas in ECGD 2 and 3 the incidence of complex ventricular arrhythmias was significantly higher in Group III than in the other 2 groups (p less than 0.05). In Group III, the complexity and frequency of ventricular arrhythmias increased both in ECGD 2 and 3 compared to ECGD 1 (p less than 0.05). Furthermore, between patients of Group II and III higher grade arrhythmias and more frequent ventricular premature beats (VPB) were noted in sudden death patients than in survivors. There was no statistical difference in mean cardiac index, left ventricular end-diastolic pressure and ejection fraction among the groups. In the ACRD 1 performed an average of 8 months after AMI, a slight decrease of ejection fraction in Group III compared to the other groups was noted (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245430 TI - [Stratification of risk in infarcts without Q wave: role of echocardiography at rest and during exertion]. AB - To assess the relation between the extent of myocardial necrosis and the presence of myocardium at risk in myocardial infarction without Q waves (NQMI) we studied by echocardiography the prevalence of jeopardized myocardium in a group of NQMI stratified on the basis of left ventricular wall motion (akinesis, hypokinesis, normal kinesis). We have studied 60 consecutive patients with non-Q myocardial infarction. Patients were examined by 2D echo at rest (V-VI day from the acute episode) and during symptoms limited bicycle ergometric test (ExT) (XX-XXX day). Regional left ventricular wall motion was evaluated as normal or asynergic (severe hypokinetic, akinetic) and the ExT was considered positive in case of new asynergic areas or ECG criteria. 2D echo at rest was technically satisfactory in 56 patients, 19 showed almost an akinetic segment (Aci) 17 had hypokinetic areas (Ipo) and 20 had normal left ventricle kinesis (Norc). Wall motion abnormalities were localized more frequently in the apex and lateral areas. During exercise 2D echo was performed in 46 patients (82%) with 23 positive tests (50%). Stratifying the population on the basis of left ventricle wall motion we observed a major number of positive tests in the group of patients with normal wall motion in comparison with those with asynergic areas at rest (Norc 66.6%, Ipo 35.7%, Aci 42.6% p less than 0.05 Nore vs Ipo and Nore vs Aci) despite the same CAD extension. These data show the heterogeneity of the NQMI that likely includes patients with transmural (asynergy group) and subendocardial MI (normal kinesis group), the latter with a higher degree of myocardium at risk. PMID- 2245431 TI - [Magnetic resonance imaging in non-Q wave infarction]. AB - The aim of this study is to evaluate magnetic resonance (MR) as a clinical tool to identify the site of non-Q myocardial infarction, when other techniques are inadequate. Ten patients underwent MR examination 3 - 15 days after the onset of symptoms. The examinations were performed with a General Electric 1.5 Tesla II unit, by means of ECG-gated MR imaging. The 10 patients were 35 to 56 years of age, 9 were men. In 5 patients it was the first myocardial infarction, in 5 patients the second. MR allowed us to identify the site of myocardial infarction: 5 inferior, 1 posterior, 2 postero-inferior, 1 apical, 2 subendocardial. Thus the MR examination is suggested in non-Q myocardial infarction to detect the site and the extent of the infarct. The MR is useful when echocardiography is technically non adequate or when it is not possible to identify regional wall motion abnormalities. We suggest to use this technique in patients with coronary artery bypass and in patients with multiple infarctions. PMID- 2245432 TI - [Evaluation of coronary anatomy and coronary circulation by transesophageal echocardiography]. AB - Nowadays the anatomy and coronary flow can be evaluated by means of various methods requiring cardiac catheterization. Transesophageal echocardiography is a new diagnostic method with great potential (excellent technical quality, stable positioning of the transducer, no lung interposition). Because of its potential we have used transesophageal echocardiography on a number of patients undergoing coronary angiography in order to investigate its reliability in estimating the anatomy and coronary flow. From the anatomical point of view 3 aspects were identified: absence of alterations affecting the vessel being explored (Criterion A); presence of non-stenotic calcific wall plaques (Criterion B); presence of stenotic calcific plaques (Criterion C). The percentage of visualization of the left main artery, the left anterior descending and the circumflex was 87%, 78% and 76% respectively. The criteria described showed varying reliability depending on the coronary portion being considered. Using the pulsed Doppler, during the transesophageal study, we obtained an adequate recording of the velocity profile of the left anterior descending in 28/37 patients. After dipyridamole infusion all velocity parameters (diastolic and systolic mean and maximum velocities) increased significantly in those patients with left anterior descending without stenosis, while remaining practically constant in those patients with significant stenosis of the left anterior descending artery. In particular the ratio between the maximum diastolic velocity recorded after dipyridamole and the velocity recorded immediately before infusion was significantly greater in those subjects with normal left anterior descending than in those with significant stenosis of the left anterior descending artery. CONCLUSIONS: transesophageal echocardiography offers new prospects in studying anatomic alterations and flow patterns of the proximal part of the left coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245433 TI - [Etiology and incidence of pure mitral insufficiency: a morphological study of 926 native valves]. AB - From July 1981 to October 1988, 1597 native valves, 926 (58%) mitral and 671 (42%) aortic, were excised. The gross and histological features of all valves were studied using routine histochemical, immunohistochemical and electron microscopy techniques. As far as mitral valve is concerned the lesions were: stenosis 263 (28.6%), stenosis + incompetence 537 (57.8%) and incompetence 126 (13.6%). Our study was limited to the valves of patients undergoing mitral valve replacement because of pure incompetence. The pathological alterations of the valves were: floppy mitral valve (FMV) 59 (46.8%), rheumatic disease (RD) 50 (39.6%), infective endocarditis (IE) 13 (10.3%), papillary muscles ischemic disease (PMID) 4 (3.1%). In the FMV group the associated lesions were: aortic valve incompetence due to floppy aortic valve and noninflammatory aortic root disease (9-15.2%), tricuspid valve incompetence (4-7.8%) and atrial septal defect (7-13.7%). The commonest complication in this group was rupture of chordae tendineae requiring urgent surgery. In the RD group there was a high incidence of active rheumatism, valvulitis and papillary muscles myocarditis (37-74%) despite the laboratory data were within normal ranges. In the IE group there was an associated aortic endocarditis in 7 patients (53.8%). The FMV was the commonest cause of pure incompetence in patients who had mitral valve replacement. Rheumatic pure mitral incompetence was always associated in our experience to signs of active rheumatic disease. PMID- 2245434 TI - [Winging effect in interatrial defect after transseptal mitral valvuloplasty: an anatomical study]. AB - In the balloon catheters the redundancy of the deflated balloon produces 2 or 3 sort of thin wings. The presence of wings can reduce the catheter "pushability" or, in certain conditions, can determine tissue lesion (winging effect). Simulating a transeptal valvuloplasty of the mitral valve by technique of the 2 balloon in human fresh heart, we studied the winging effect over the interatrial septum in 12 hearts; in the first 6 the atrial septum was dilated with a 6 mm balloon (Group A), in the second 6 the atrial septum was dilated with a 10 mm balloon (Group B). The procedure was completed introducing consecutively 2 bigger balloons (15 + 20 mm). We suppose that the winging effect of the 2 bigger balloons (15 + 20 mm) could counter balance the theoretical advantage of a small balloon (6 mm). The atrial septal defect (ASD) after septal dilatation was 5.0 +/ 0.59 mm x 1.56 +/- 0.25 mm (long axis x short axis) in Group A and 6.53 +/- 0.35 x 2.16 +/- 0.39 mm in Group B (p less than 0.01). The final ASD (after introducing the 2 bigger balloons) was 7.04 +/- 1.06 x 2.36 +/- 0.57 mm in Group A and 7.03 +/- 0.18 x 2.16 +/- 0.32 mm in Group B (NS). Our data show that the winging effect can determine biological negative effects. PMID- 2245435 TI - [Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. AB - Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis. A 10% reduction in cholesterol levels can reduce the risk of coronary heart disease by 15%. However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism. The efficacy and the tolerability of simvastatin (a inhibitor of HGM-CoA reductase) with that of gemfibrozil (a fibric acid derivative, which can reduce the VLDL level) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide. After 10 weeks standard hypolipidemic diet and hydrochlorothiazide (25 mg od) therapy, 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments: simvastatin, 20 mg od, gemfibrozil, 600 mg bid or placebo, while continuing dietetic and diuretic treatment. After 24 weeks treatment, simvastatin induced a 37% reduction in cholesterol plasma levels, a 9% increase of HDL and a 16% reduction of LDL. APO-A1 showed a 4% increase, while APO-B showed a 3% reduction. Gemfibrozil induced a 20% reduction in plasma triglycerides and a 13% decrease in plasma cholesterol, with a significant 19% increase in HDL and a 11% reduction in LDL. No significant variations in any of the lipid parameters monitored were observed in the placebo group. Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo. Simvastatin, however, resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions. PMID- 2245436 TI - [Restrictive cardiomyopathy in eosinophilic leukemia: echocardiographic and nuclear magnetic resonance aspects]. AB - This paper reports a case of endomyocardial disease due to hypereosinophilic syndrome. Two-dimensional echocardiography showed prevalent right ventricular involvement, with obliteration of the apex due to an echogenic mass progressively filling the whole ventricular cavity. RMN accurately defined the presence and the characteristics of the infiltrative mass in the right ventricular chamber. A different intensity of spin-echo imaging sequence was used to differentiate between thrombotic and infiltrative leukemic images. It is concluded that prevalent right ventricular involvement during eosinophilic endomyocardiopathy is a relatively rare disease which can be detected and evaluated by the use of echocardiography and RMN studies. PMID- 2245437 TI - Fatal measles myocarditis. AB - A case of fulminant measles myocarditis is reported. Diagnosis has been obtained at autopsy, due to absence of skin rash, by identification of measles giant cells in the myocardium and by positive reaction of myocardial tissue to measles specific immunoperoxidase. Unusual outcome is interpreted as due to defective cell-bound immunity and extentive involvement of myocardial microcirculation. PMID- 2245438 TI - Characterization of bone-derived chondrogenesis-stimulating activity on embryonic limb mesenchymal cells in vitro. AB - Demineralized bone matrix contains factors which stimulate chondrogenesis and osteogenesis in vivo. A water-soluble extract of bone has been shown to stimulate chondrogenesis in vitro in embryonic limb mesenchymal cells (Syftestad, Lucas & Caplan, 1985). The aim of this study was to analyse the cellular mechanism of the bone-derived chondrogenesis-stimulating activity, with particular attention on how normal requirements for chondrogenesis may be altered. The effects of bovine bone extract (BBE) on chondrogenesis in vitro were studied using micromass cultures of chick limb bud mesenchyme isolated from embryos at Hamburger-Hamilton (HH) stage 23/24, an experimental system which is capable of undergoing chondrogenic differentiation. Bovine diaphyseal long bones were demineralized and extracted with guanidine-HCl to prepare BBE (Syftestad & Caplan, 1984). High density mesenchyme cultures (30 x 10(6) cells/ml) were exposed to different doses of BBE (0.01-1.0 mg ml-1) and chondrogenesis was quantified based on cartilage nodule number and [35S]sulphate incorporation. BBE was tested on micromass cultures of varying plating densities (2-30 x 10(6) cells/ml), on cultures of 'young' limb bud cells (HH stage 17/18), and on cultures enriched with chondroprogenitor cells obtained from subridge mesoderm. Since poly-L-lysine (PL) has recently been shown (San Antonio & Tuan, 1986) to promote chondrogensis, PL and BBE were introduced together in different doses, in the culture medium, to determine if their actions were synergistic. Our results show that BBE stimulates chondrogenesis in a dose-dependent manner and by a specific, direct action on the chondroprogenitor cells but not in normally non-chondrogenic, low density or 'young' limb bud cell cultures. The effects of PL and BBE are additive and these agents appear to act by separate mechanisms to stimulate chondrogenesis; PL primarily enhances nodule formation, and BBE appears to promote nodule growth. PMID- 2245439 TI - Proliferative activity of primary breast cancer and of synchronous lymph node metastases evaluated by [3H]-thymidine labelling index. AB - The [3H]-thymidine labelling index ([3H]TdR LI) has been used to evaluate and comparatively analyse the proliferative activity of different tumour lesions from the same patient. The analysis was performed on the primary tumour and its synchronous lymph node metastasis from 210 patients operated on for breast cancer. A direct relation was observed between the proliferative activity of the two different lesions (Spearman correlation coefficient = 0.46, P less than 0.0001), but there was considerable scatter amongst the data. The [3H]TdR LI of primary and of metastatic lesions belonged to the same proliferation classes in only 47% of the cases. Higher or lower [3H]TdR LI values, categorized on the basis of the tertiles of the frequency distribution, occurred in the node metastasis than in the primary tumour in an almost similar percentage of the remaining cases. Menopause, receptor status and pathological features did not affect interlesion kinetic patterns. The prognostic role of the proliferative activity of the two different lesions was investigated on 107 patients with stage II tumours homogeneously treated with surgery and systemic adjuvant therapy. Relapse-free survival at 3 years was significantly affected by the proliferative activity of the primary tumour but not by that of the lymph node metastasis. PMID- 2245440 TI - Mathematical model analysis of mouse epidermal cell kinetics measured by bivariate DNA/anti-bromodeoxyuridine flow cytometry and continuous [3H]-thymidine labelling. AB - In a previous study the epidermal cell kinetics of hairless mice were investigated with bivariate DNA/anti-bromodeoxyuridine (BrdU) flow cytometry of isolated basal cells after BrdU pulse labelling. The results confirmed our previous observations of two kinetically distinct sub-populations in the G2 phase. However, the results also showed that almost all BrdU-positive cells had left S phase 6-12 h after pulse labelling, contradicting our previous assumption of a distinct, slowly cycling, major sub-population in S phase. The latter study was based on an experiment combining continuous tritiated thymidine [( 3H]TdR) labelling and cell sorting. The purpose of the present study was to use a mathematical model to analyse epidermal cell kinetics by simulating bivariate DNA/BrdU data in order to get more details about the kinetic organization and cell cycle parameter values. We also wanted to re-evaluate our assumption of slowly cycling cells in S phase. The mathematical model shows a good fit to the experimental BrdU data initiated either at 08.00 hours or 20.00 hours. Simultaneously, it was also possible to obtain a good fit to our previous continuous labelling data without including a sub-population of slowly cycling cells in S phase. This was achieved by improving the way in which the continuous [3H]TdR labelling was simulated. The presence of two distinct subpopulations in G2 phase was confirmed and a similar kinetic organization with rapidly and slowly cycling cells in G1 phase is suggested. The sizes of the slowly cycling fractions in G1 and G2 showed the same distinct circadian dependency. The model analysis indicates that a small fraction of BrdU labelled cells (3-5%) was arrested in G2 phase due to BrdU toxicity. This is insignificant compared with the total number of labelled cells and has a negligible effect on the average cell cycle data. However, it comprises 1/3 to 1/2 of the BrdU positive G2 cells after the pulse labelled cells have been distributed among the cell cycle compartments. PMID- 2245441 TI - Basement membrane components stimulate epithelialization of intestinal defects in vivo. AB - Subepithelial tissues have an important role in the structure and function of the intestinal epithelium. Basement membrane components (BMC) stimulate epithelial cell migration and differentiation in vitro. The aim of this study was to determine the effect of BMC and/or interstitial tissue collagen (type I) on the in vivo intestinal regenerative response to intestinal patching. Twenty rabbits had two 2 x 5 cm ileal defects patched with the serosal surface of adjacent caecum. Group 1 (n = 5) were controls; group 2 (n = 5), group 3 (n = 5) and group 4 (n = 5) had collagen, collagen plus BMC, and BMC respectively applied to the distal patched defect. Animals were killed at 7 d and evaluated grossly for epithelialization and contraction of the defects. Epithelial coverage was greatest in the distal patch of group 4 animals (62 +/- 9%) and was significantly greater than the group 4 proximal patch and control values (43 +/- 7 and 40 +/- 14%, P less than 0.05). Contraction was similar in all groups (38 +/- 5 to 45 +/- 5%). Crypt cell production rate, villus height, and disaccharidase activities were similar in all groups. BMC stimulated epithelialization via a local mechanism since only the distal patch was affected. Type I collagen did not stimulate epithelialization and inhibited the effect of BMC. Since crypt cell production rate was similar in all groups, the enhanced epithelialization seen with BMC is primarily due to increased cell migration. PMID- 2245442 TI - Ultraviolet B irradiation induces epidermal regeneration with rapidly cycling cells. AB - The left flank of hairless mouse skin was irradiated with a minimal erythema dose of ultraviolet B (UVB) light at 297 nm (25 mJcm-2), while the right flank served as untreated control. The alterations in epidermal growth kinetics induced by this UVB dose were studied with the percentage of labelled mitoses (PLM) technique during the period of increased proliferation. Thirty hours after irradiation, when a large cohort of cells appears in S phase, each animal was injected intra-peritoneally with 50 microCi tritiated thymidine [( 3H]-TdR). The number of labelled basal and suprabasal cells, as well as their localization in epidermis were registered in histological sections at short intervals up to 48 h after the [3H]-TdR pulse. Labelled mitoses were also counted in the same specimens. The results showed a four-fold increase of the high initial number of labelled cells in UVB-exposed epidermis within 18 h of the pulse injection, and a six-fold increase after 36 h. In control epidermis, where the starting value of the labelling index was much lower, there was only a three to four-fold increase in the number of labelled cells during the period studied. The PLM and the labelling index data were consistent with an average cell cycle time of approximately 10-12 h for UVB-exposed cells, in contrast to about 30 h for the fastest cycling population in control epidermis. The PLM curve also indicated a prolonged S phase duration in UVB-exposed epidermis compared with controls. In addition, labelled cells were seen in the suprabasal layer as early as 6 h after the [3H]-TdR injection and within 36 h labelled cells had reached the outermost layer of nucleated cells, indicating a reduced transit time through epidermis. The present study shows that a minimal erythema dose of UVB light at 297 nm induced a period of increased transit time through the S phase, combined with rapid cell proliferation, leading to an overall shortening of the epidermal cell cycle time. The cohort of cells labelled with [3H]-TdR 30 h after irradiation seemed to proceed as a wave of partially synchronized cells through the cell cycle for more than two rounds, which is comparable with the cell kinetic perturbations observed in regenerating mouse epidermis. PMID- 2245443 TI - Lysosomal inhibitors stimulate resting NIH 3T3 cells to proliferate. AB - Lysosomal inhibitors (amino acid methyl esters) and platelet-derived growth factor stimulate resting NIH 3T3 cells to enter the S period. Incubation of cells in medium containing lysosomal inhibitors causes an increase in protein accumulation and does not disrupt lysosomes. The results indicate that proliferative homeostasis depends partially on the metabolic status of the cell and that catabolic processes activated in resting cells negatively influence prereplicative reactions. PMID- 2245444 TI - Measurement of c-myc protein content and cell cycle kinetics of normal and spontaneously transformed murine mastocytes by bivariate flow cytometry. AB - Progressive in vitro culturing of interleukin-3 (IL-3) dependent normal murine mastocytes (PB-3) resulted in a variant cell line (PB-1) able to grow without exogenous IL-3 and which was tumorogenic in syngenic mice. Bivariate flow cytometry was used to evaluate the c-myc protein and DNA content of PB-3 and PB-1 cells. The c-myc protein was detected by specific monoclonal antibodies. Kinetic characteristics of PB-3 and PB-1 cell lines, namely, the duration of the G1, S and G2 + M cell cycle phases were also evaluated using the bromodeoxyuridine (BrdU) pulse-chase method and BrdU/DNA flow cytometry. Levels of c-myc protein in PB-1 cells were about two-fold higher than those of PB-3 cells in all cell cycle phases. Mean duration of the cell cycle (Tc) was 15.3 h for PB-3 cells and 12.4 h for PB-1 cells. Shortening in Tc for the transformed cells was due to a decrease of nearly 30% in mean duration of the G1 phase (from 8 h to 5.7 h). No significant differences were found in the duration of the S and G2 + M phases. These results indicate that acquired IL-3 independency in vitro and tumorogenicity of PB-1 cells were accompanied by a doubling of c-myc protein level and by a parallel shortening, or bypass, of the regulatory events within the G1 phase of the cell cycle. PMID- 2245445 TI - Vasopressin-enhanced urea transport by rat inner medullary collecting duct cells in culture. AB - The distal inner medullary collecting duct (IMCD) is critical in the urinary concentrating process, in part because it is the site of vasopressin (AVP) regulated permeability to urea. The purpose of these experiments was to develop a cell culture model of the IMCD on permeable structure and to characterize the responsiveness to AVP. Rat IMCD cells were grown to confluence on collagen-coated Millipore filters glued onto plastic rings. To assess the time required to achieve confluence, the transepithelial resistance was measured periodically and was found to be stable after 2 weeks, at a maximal value of 595 +/- 22 omega cm2. In separate monolayers the effect of AVP on inulin and urea permeability was determined. While inulin permeability was unchanged after AVP, urea permeability increased from 6.0 +/- 0.4 to peak values of 16.0 +/- 3.8 (10 nM), 23.1 +/- 3.9 (1 microM) and 28.1 +/- 4.9 (10 microM) x 10(-6) cm s-1 (n = 24). In 10 other monolayers, after the addition of 1 mM 8-Br-cAMP, urea permeability increased from 5.1 +/- 0.3 to 8.1 +/- 1.6 x 10(-6) cm s-1 and, after 8-Br-cAMP + 3-isobutyl 1-methylxanthine, to 12.2 +/- 0.7 x 10(-6) cm s-1. We conclude that rat IMCD cells grown in culture exhibit the characteristics of a 'tight' epithelium. Inulin and urea permeability are not different in the absence of AVP, consistent with high resistance junctional complexes. Furthermore, IMCD cells retain the capacity for AVP-regulated urea permeability, a characteristic feature of this nephron segment in vivo. PMID- 2245446 TI - Mutagenic effects of brief exposure to bromodeoxyuridine on mouse FM3A cells. AB - The time- and dose-dependency of the mutagenic effects of bromodeoxyuridine (BrdU), a thymidine analogue used for cell kinetics studies in vivo and in vitro, were investigated in FM3A cells. Cells incubated with 50-1000 microM BrdU for 72 h showed some inhibition of growth. Cells cultured in BrdU-free medium for 3 d after a 30 min or 2 h exposure to BrdU showed no growth inhibition, while those previously exposed for 24 h to BrdU showed retarded growth. After a 30 min exposure, 60% of cells were labelled with BrdU; after 2 h 70%; and after 24 h almost 100%. After incubation in BrdU-free medium for 3 d (the time required for this cell line to express mutation), cells previously treated for 30 min or 2 h showed reduced BrdU positivity, whereas almost 100% of those treated for 24 h remained BrdU positive. The mutation rate, determined by the number of colonies resistant to ouabain (2 mM) and 6-thioguanine (10 microM) 3 d after exposure to BrdU, was not affected by a 30 min treatment with up to 1000 microM BrdU. Cells treated for 1 or 2 h showed increased resistance to ouabain after exposure to BrdU at concentrations above 100 microM; cells treated for 12 or 24 h showed an increased mutation rate at BrdU concentrations above 50 microM. The number of colonies resistant to 6-thioguanine did not increase in cells treated with BrdU at concentrations up to 1000 microM for 1, 12 or 24 h. We cannot conclude with certainty that brief exposure to BrdU does not modulate DNA to the point of mutation. This study may serve as a guideline for limiting the dose and time of exposure to BrdU for cell kinetics studies in vivo and in vitro. PMID- 2245447 TI - Ultrastructural changes of liver parenchyma following digitonin-pulse perfusion of rat liver. AB - It has been shown that pulse perfusion of rat liver with a digitonin-containing medium results in a highly zonated hepatocyte permeabilization, allowing selective sampling of cytosolic constituents from periportal and perivenous (centrolobular) hepatocytes "in situ". In the present paper we provide an ultrastructural evaluation of the perfusion method. Identical changes in hepatocytes from affected periportal and perivenous zones are found. Affected hepatocytes appear light (electron-lucent) in electron micrographs with a sharp transition to normal hepatocytes. The most conspicuous ultrastructural findings are: (1) transformation of the sinusoidal part of the light hepatocytes, the lipocyte processes and the endothelium of affected zones apparently unifying into a continuous layer dominated by disrupted plasma membranes and 7-nm filaments; (2) deposition of osmiophilic digitonin-cholesterol complexes along the sinusoidal plasma membranes of affected zones; and (3) reduction of the cytoplasmic matrix (cytosol) in the light hepatocytes, a dilation of the mitochondrial intermembrane space with a preserved mitochondrial matrix, and a dilation of cisternae of the granular endoplasmic reticulum. The ultrastructural findings are consistent with marker-enzyme activity measured in eluates from digitonin-perfused livers, except that lysosomes appear intact, apparently contrasting with the observed eluation of amyloglucosidase (Quistorff et al. 1985). PMID- 2245448 TI - Effect of carbamylcholine on Harderian gland morphology in rats. AB - To determine the effect of cholinergic secretagogue on the Harderian gland of rats, several light- and electron-microscopic parameters were morphometrically assessed at different time intervals after carbamylcholine injection. In controls, two types of glandular cells (type A cells having 40-55 large vacuoles per cell profile and type B cells containing 30-38 smaller vacuoles per cell profile) and myoepithelial cells were recognized. At 5 min after injection of carbamylcholine, when rats secreted "bloody tears", many alveoli showing narrower lumina and exocytotic figures in both types of cells were observed. Some vacuoles, which were covered by thin cytoplasmic sheets, protruded into the alveolar lumina. However, there was no evidence of apocrine or holocrine secretion. At 30 min and 120 min after injection, most of the alveolar lumina were dilated, and a pronounced decrease in the number of vacuoles in the glandular cells was observed. At 300 min after injection, the secretory vacuoles in both cell types reaccumulated. Transitional forms between the two cell types were not observed. The two types of Harderian gland cells can therefore be considered independent populations rather than different secretory stages of the same cell. It appears that the secretory process of the Harderian gland of rat is affected by cholinergic stimulation of the two types of glandular cells and of myoepithelial cells. PMID- 2245449 TI - Innervation of the mink pineal gland with neuropeptide Y (NPY)-containing nerve fibers. An experimental immunohistochemical study. AB - An immunohistochemical investigation of the mink pineal gland was performed by use of antibodies raised in rabbits against neuropeptide Y (NPY) and Cys-NPY (32 36)-amide recognizing neuropeptide Y with an amidation at position 36 (NPYamide). NPY-immunoreactive nerve fibers were located predominantly in the rostral part of the pineal gland and in the pineal stalk. Immunoreactive nerve fibers were found throughout the pineal gland, but the number of fibers in the caudal part of the gland was low. The fibers were present both in the perivascular spaces and between the pinealocytes. Many NPY-immunoreactive fibers were also located in the posterior and habenular commissures; some of these fibers were connected with the fibers in the rostral part of the mink pineal gland, indicating that at least some of the NPY-immunoreactive nerve fibers are of central origin. The nerve fibers immunoreactive to amidated NPY were distributed in a similar manner. However, the number of fibers immunoreactive to NPYamide was lower than the number of fibers immunoreactive to NPY itself. After removal of the superior cervical ganglia bilaterally 22 days or 12 months before sacrifice, NPY immunoreactive nerve fibers remained in the gland. This immunohistochemical study of the mink pineal gland therefore shows that the NPY/NPYamide-immunoreactive nerve fibers innervating the pineal gland in this species are a component of the central innervation or originate from extracerebral parasympathetic ganglia. PMID- 2245450 TI - Complex relationships between the pineal organ and the medial habenular nucleus pretectal region of the mouse as revealed by S-antigen immunocytochemistry. AB - S-antigen-immunoreactive pinealocytes located in the deep portion of the pineal organ of inbred and wild pigmented mice give rise to long, beaded processes penetrating into the habenular and pretectal regions. In addition, the medial habenular nuclei and the pretectal area contain S-antigen-immunoreactive perikarya, which resemble pinealocytes in size, shape and immunoreactivity and are considered as "pinealocyte-like" epithalamic cells. Immunoblotting techniques reveal that a single protein band of approximately 48 kDa molecular weight accounts for this immunoreactivity. As shown with the use of the electron microscope, the majority of the S-antigen-immunoreactive processes is closely apposed to immunonegative neuronal profiles and perikarya of the habenular and pretectal regions. S-antigen-immunoreactive processes and perikarya of both pinealocytes of the deep pineal organ and pinealocyte-like epithalamic cells may form the postsynaptic element in conventional synapses involving axons provided with clear synaptic vesicles. Thus, certain mammalian pinealocytes may receive and transmit signals via point-to-point connections resembling neuro-neuronal contacts. These results challenge the concept that the mammalian pineal organ exerts its influence exclusively via the release of melatonin into the general circulation. Furthermore, they provide evidence (i) that neuronal circuits not involving the sympathetic system participate in the regulation of pineal functions in mammals, and (ii) that intimate histogenetic and functional relationships exist between the pineal organ and the habenular-pretectal nuclei in mammals. PMID- 2245451 TI - Stress fibers in the mesenteric mesothelial cells of the large intestine of the bullfrog, Rana catesbeiana. AB - Actin-containing cytoplasmic fibers were visualized in the mesenteric mesothelial cells of the large intestine of bullfrog tadpoles by rhodamine-phalloidin staining of en face preparations of mesothelial cells. These fibers were concurrently stained by immunofluorescence using antibodies to myosin or alpha actinin. Electron microscopy showed the presence of bundles of microfilaments in the basal cytoplasm of the cells. Such fibers in the mesothelial cells may be comparable to the stress fibers present in cultured cells. The mesothelial cells initially formed axially oriented stress fibers when they changed from a rhombic to a slender spindle-like shape. On the other hand, stress fibers disappeared as cells transformed from elongated to polygonal shapes during the period of metamorphic climax. Expression of stress fibers in these cells appears to be related to the degree of tension loaded on the mesentery, which may be generated by mesenteric winding. These stress fibers in the mesothelial cells may serve to regulate cellular transformation. They may also help to maintain cellular integrity by strengthening the cellular attachment to subepithelial tissue against tensile stress exerted on the mesentery. PMID- 2245452 TI - Ontogeny of the carotid body and glomus cells distributed in the wall of the common carotid artery and its branches in the chicken. AB - Developmental patterns of immunoreactivity for serotonin and neuropeptide Y were investigated immunohistochemically in the carotid body and glomus cells in the wall of the common carotid artery and around its branches of chickens at various developmental ages. The development of peptidergic nerve fibers was also studied. Serotonin immunoreactivity began to appear in the glomus cells of the carotid body and around arteries at 10 days of incubation and became very intense from 12 days onwards. Neuropeptide Y immunoreactivity also appeared in these cells at 10 days, became intense at 14 days, and was sustained until 20 days. After hatching, neuropeptide Y immunoreactivity in the carotid body rapidly decreased with age and almost disappeared at postnatal day 10. However, it persisted for life in the glomus cells distributed in the wall of the common carotid artery. Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive fibers first penetrated into the carotid body parenchyma at 12 days of incubation. These peptidergic nerve fibers in the carotid body and glomus cell groups in and around arteries gradually increased with age, and approached the adult state at 18 days of incubation. Only a few galanin- and vasoactive intestinal peptide (VIP) immunoreactive fibers were observed in the late embryonic carotid bodies. They rapidly developed after hatching and reached adult numbers at postnatal day 10. During late embryonic and neonatal development, considerable numbers of met enkephalin-immunoreactive fibers were detected in the connective tissue encircling the carotid body. PMID- 2245453 TI - Organ culture of human seminiferous tubules: a useful tool to study the role of nerve growth factor in the testis. AB - Seminiferous tubules from human testes were mechanically isolated, the cut edges were sealed, and the tubules were cultured in medium free of fetal calf serum (FCS). Degeneration of germ cells occurred during the culture period and was paralleled by a disruption of the seminiferous epithelium, a disturbance in morphology and function of Sertoli cells, and a thickening of the lamina propria. However, when tubules were cultured for 5 days in the presence of FCS, degeneration of the spermatogenic tissue was reduced. FCS increased the mitotic activity of germ cells, but did not maintain normal morphology and function of Sertoli cells and cellular elements of the lamina propria. The thickening of the tubular wall concurred with a change in phenotype of lamina-propria cells from myoid to fibroblastic. Addition of nerve growth factor (NGF) to the culture medium (i) maintained the myoid phenotype of lamina-propria cells, (ii) prevented thickening of the tubular wall, and (iii) stabilized Sertoli cell morphology and function. The effects of NGF appeared to depend on the trophic effects of FCS, since NGF alone had no influence on the maintenance of a regular morphology of the spermatogenic epithelium. The present results indicate a decisive role for NGF in stabilizing specific functions of seminiferous tubules. PMID- 2245455 TI - Migraine treatment with nicardipine. AB - A novel calcium entry blocker, nicardipine, has been tested using a dosage of 20 mg twice a day against placebo on 30 patients suffering from migraine without aura, according to a double-blind, cross-over design; overall duration of the study was four months (two with nicardipine and two with placebo). Migraine parameters such as monthly frequency, mean intensity and mean duration of attacks were monitored. Two indexes were also calculated: index A (monthly frequency x mean intensity) and index B (monthly frequency x mean intensity x mean duration). All the parameters considered and the two indexes showed a marked and significant improvement after nicardipine treatment in comparison to both placebo and pre study scores. Detailed analysis of the cross-over results showed that improvement obtained with nicardipine lasted some time after the drug was discontinued. Nicardipine did not alter the blood and attention tests performed and caused few side effects. PMID- 2245454 TI - Immunoreactivity to the pancreatic polypeptide family in the nervous system of the adult human blood fluke, Schistosoma mansoni. AB - The presence and distribution of neuropeptides belonging to the pancreatic polypeptide family have been demonstrated by an indirect immunofluorescence technique in the nervous systems of adult male and female Schistosoma mansoni. Seven antisera of differing regional specificity to pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) were employed on both whole-mount and cryostat-sectioned material. Positive immunoreactivity (IR) was obtained with all antisera except an N-terminally-directed antiserum to NPY. In the CNS, immunoreactivity was restricted to cell bodies and nerve fibres in the anterior ganglia, central commissure and dorsal and ventral nerve cords of both sexes, whereas, in the PNS, positive-IR was present in the plexuses innervating the subtegumental musculature and the oral and ventral suckers. Intense immunoreactivity was observed in a plexus of nerve fibres and cell bodies in the lining of the gynaecophoric canal and in fine nerve fibres innervating the dorsal tubercles of the male. In contrast, in the female, strong immunoreactivity was evident in nerve plexuses innervating the lining of the ovovitelline duct and in the wall of the ootype, but most notably in a cluster of cells in the region of Mehlis' gland. Results suggest that molecules with C-terminal homology to the PP family are present in S. mansoni. These peptides would appear to be important regulatory molecules in the parasite's nervous system and may play a role in the control of egg production. PMID- 2245456 TI - Changes in cerebral haemodynamics in cases of post-lumbar puncture headache: a prospective transcranial Doppler ultrasound study. AB - We used transcranial Doppler ultrasonography in 45 patients to investigate if changes in haemodynamics in the major arteries of the brain base occurred after lumbar puncture and whether or not patients with or without post-lumbar puncture headache differ with respect to their cerebral haemodynamic parameters before and after lumbar puncture. Before lumbar puncture, patients with post-lumbar puncture headache differed from patients without post-lumbar puncture headache in that they showed significantly higher flow velocities and significant asymmetry of flow velocities with lateralization to the right (p less than or equal to 0.05). Patients without post-lumbar puncture headache, on the other hand, showed non significant flow velocity lateralization to the left. Forty-eight hours after lumbar puncture, both groups demonstrated symmetrical flow velocities. In addition, only patients with post-lumbar puncture headache showed a significant reduction in the flow velocity of the right middle cerebral artery (p less than or equal to 0.05). These findings suggest that it is not only absolute flow velocity that plays a part in the event of headache, the interhemispheric relation of cerebral haemodynamics also plays a fundamental role. PMID- 2245457 TI - Oculomotor disturbances in patients with tension headache treated with acupuncture or physiotherapy. AB - Forty-eight female patients with chronic tension headache were randomized into two treatment groups--acupuncture and physiotherapy. The patients were examined using oculomotor tests. Intensity of the headache and tenderness of the trapezius muscles were assessed in accordance with graded scales. The mean velocity gain for smooth pursuit eye movements improved for all target velocities both in the physiotherapy group and in the acupuncture group. The latency was reduced for all three gaze angles in the physiotherapy group while no improvement occurred in the acupuncture group. There was a reduction of headache intensity in both groups while tenderness of the trapezius muscles was reduced in the physiotherapy group but unchanged in the acupuncture group. A significant correlation was found between average of the mean velocity gain and tenderness of the trapezius muscles. PMID- 2245458 TI - Muscle tenderness in tension headache treated with acupuncture or physiotherapy. AB - Sixty-two female patients with chronic tension headache were randomized into two treatment groups--acupuncture and physiotherapy. The intensity of headache, muscle tenderness and neck mobility was assessed before and after treatment. Thirty healthy women were used for comparison. Before treatment it was found that muscle tenderness was increased and neck rotation was reduced in the patient group compared with controls. There was a significant correlation between the intensity of headache and muscle tenderness. After treatment, the intensity of headache and muscle tenderness were reduced in both treatment groups. The headache was more improved in the physiotherapy group, and there was a marked reduction in the intake of analgesics. The tenderness was reduced in all muscles tested in the physiotherapy group but only in some of the muscles after acupuncture. The limitation of neck rotation was not influenced by either treatment. PMID- 2245459 TI - Hemicrania continua. The first Spanish case: a case report. AB - The case of a patient suffering from strictly unilateral continuous headache, absolutely responsive to indomethacin is reported. This is the first Hemicrania continua case to be documented in Spain. The tyramine test resulted in anisocoria with the smaller pupil on the symptomatic side. A second tyramine test after one week on 75 mg indomethacin per day failed to produce anisocoria. Treatment was reduced to 25 mg indomethacin per day, and this dose was sufficient to control the headache completely. PMID- 2245460 TI - Ovarian steroid levels in migraine with and without aura. AB - Radioimmunoassays were used to measure interictal levels of ovarian steroids (oestradiol, total oestrogens and progesterone) in migraine patients at the onset of menses and coincident with the luteinizing hormone surge preceding ovulation. Results of these verified biochemically-contrasting points of the ovarian cycle were used to compare 13 migraine patients without aura and 6 migraine patients with aura with 17 non-migraine women. No group differences were found for physiological basal levels of ovarian steroids measured at menses. Preceding ovulation elevation in oestradiol levels relative to normal was found in migraine patients with aura but not in migraine patients without aura. These results suggest that a variation in oestradiol levels is an important factor in the different clinical expressions of migraine. PMID- 2245461 TI - Low doses of propranolol are effective as migraine prophylaxis. PMID- 2245462 TI - Sleep deprivation headache. AB - Headaches due to insufficient or interrupted sleep are generally labelled "tension headaches" of psychogenic origin. In 25 healthy subjects, variable amounts of sleep loss (1-3 h for 1-3 nights) caused headaches lasting from 1 h to all day. The headache was most frequently a dull ache, a heaviness or a pressure sensation felt in the forehead and/or at the vertex. Simple analgesics, purchaseable without a doctor's prescription, completely or markedly reduced the head pain in 20-60 min. Headaches due to insufficient sleep differ from tension headaches in their site, duration and response to analgesics. Assuming that pain implies a regional dysfunction, headaches caused by sleep loss provide support for the notion that sleep has a restorative function in the brain. PMID- 2245463 TI - Platelet aggregation of migraineurs during and between attacks. AB - Platelet aggregation induced by ADP, collagen and platelet-activating factor was studied in common (migraine without aura) and classical migraine (migraine with aura) patients during and between attacks. The EC50* values for ADP and platelet activating factor were significantly higher, whilst that for collagen was significantly lower in classical migraine patients during headache-free intervals compared to healthy volunteers. The EC50 values obtained for common migraine sufferers during symptom-free periods were similar to those of controls. During attacks, the EC50 value for ADP, but not for collagen and platelet-activating factor, was significantly higher than that of the controls. In healthy subjects a positive correlation was found between ADP and collagen-induced aggregation. In contrast, there was a U-shaped correlation matrix in classical migraine patients. The present observations show that platelet aggregation is altered in migraine patients and this raises the possibility that platelet-activating factor may be involved in the pathogenesis of migraine. PMID- 2245464 TI - How caloric vestibular irritation influences migraine attacks. AB - Stimulation of the vestibular system by cold irritation of the ear was performed in 12 patients during a migraine attack. In eleven of the subjects the headache was changed. The changes varied from completely disappeared to a slight decrease. The duration of the changes was either several minutes, during the vestibular irritation, or days. All changes were related to the induced sensation of vertigo. We discuss the probable mechanisms of these vestibular influences. PMID- 2245465 TI - Neuromagnetic fields in migraine: preliminary findings. AB - Neuromagnetic signals consistent with spreading cortical depression have been observed in 9 of 12 migraine patients studied, but not in normal controls (out of 8 studied) or in patients with non-migrainous headache (4 studied). These signals consist of large amplitude, usually biphasic waveforms presumably arising from the onset or offset of spreading cortical depression in a sulcus, and prolonged attenuation of magnetic amplitudes, associated with suppressed neuronal activity. Techniques are described which recognize various kinds of artefacts and which distinguish changes in state of arousal of the patient from the presumed spreading cortical depression signals. PMID- 2245466 TI - Alpha rhythm in classical migraine (migraine with aura): abnormalities in the headache-free interval. AB - The alpha rhythm of 18 patients with classical migraine (migraine with aura) was studied by EEG spectrum analysis for evidence of neural abnormalities during the asymptomatic period. The temporal relationship of the findings to attacks was studied by serial records in 11 cases. Increased frequency dispersion and frequency asymmetries of the alpha rhythm were found. The records were, however, mostly normal when separated from attacks by at least 10 asymptomatic days. The abnormalities increased significantly before the onset of prodromal symptoms and clearly outlasted the headache phase. The results give evidence of a fluctuating asymmetric neural disorder in classical migraine. PMID- 2245467 TI - Sex steroids and cluster headache: hypotheses. AB - The pathophysiological significance of the changes in gonadal function observed in cluster headache is far from clear. Some features of the disease, such as the sex predominance, the lateralization of symptoms and the character of pain itself may be connected to some biological effects of gonadal steroids. PMID- 2245468 TI - Occupational stress in migraine--is weekend headache a myth or reality? AB - To determine whether or not the frequency of migraine attacks increased at weekends in employed patients and if so, whether or not this was related to the type of migraine, 35 female patients prospectively recorded the presence or absence of migraine attacks daily over a six-week period. They were also asked to estimate the frequency with which emotional factors predisposed to their migraine attacks and to provide details of their occupation. A diagnosis of common (migraine without aura) or classical migraine (migraine with aura) was made according to both the criteria of the Ad Hoc Committee on the Classification of Headache and those of the International Headache Society. Eleven percent and 6% of patients, respectively, felt that emotional factors "usually" or "always" predisposed to migraine attacks. There was no significant increase in the frequency of migraine attacks at weekends in either the total group or in the employed patients. Similarly, the type of migraine made no difference to the results. There was therefore no evidence for a delayed onset of migraine at weekends related to the weekday stress of employment. PMID- 2245469 TI - Evaluation of clinical criteria for cluster headache with special reference to the classification of the International Headache Society. AB - The diagnostic criteria issued by the International Headache Society (IHS) (1988) and those of the World Federation of Neurology (WFN) (1969) were evaluated vis-a vis 163 consecutive cases of cluster headache diagnosed according to the criteria of Ekbom (1970). The agreement between the IHS and Ekbom criteria was very good (96.9%). The difference was explained by five patients who all lacked local autonomous symptoms and signs (conjunctival injection, lacrimation, etc.). At least one of these signs is mandatory according to the IHS and thus the patients escaped a definite diagnosis. Agreement between the WFN and Ekbom criteria was 84.0% (n = 163) and between the WFN and IHS criteria only 76.0% (n = 158). PMID- 2245470 TI - Orgasm--a new trigger factor of cluster headache? PMID- 2245471 TI - Genetic control of plasmid DNA double-strand gap repair in yeast, Saccharomyces cerevisiae. AB - The repair of double-strand gaps (DSGs) in the plasmid DNA of radiosensitive mutants of Saccharomyces cerevisiae has been analyzed. The proportion of repair events that resulted in complete plasmid DNA DSG recovery was close to 100% in Rad+ cells. Mutation rad55 does not influence the efficiency and preciseness of DSG repair. The mutant rad57, which is capable of recombinational DNA DSB repair, resulted in no DSG recovery. Mutation rad53 substantially inhibits the efficiency of DSG repair but does not influence the precision of repair. Plasmid DNA DSG repair is completely blocked by mutations rad50 and rad54. PMID- 2245472 TI - Fate of highly expressed proteins destined to peroxisomes in Saccharomyces cerevisiae. AB - Import of proteins into organelles usually requires a cis-acting targeting signal. Analysis of various hybrid proteins, consisting of mouse DHFR and parts of catalase A from Saccharomyces cerevisiae, revealed that fusion proteins containing the N-terminal 126 amino acids, or less, of catalase A remain in the cytosol whereas fusion proteins containing 140, or more, N-terminal amino acids of catalase A form large aggregates inside the cell. These protein bodies, which lack a surrounding membrane, copurified with peroxisomes on cell fractionation. The peroxisomal targeting signal of catalase A does not reside at the C-terminus or at the N-terminus. PMID- 2245473 TI - Isolation and properties of yeast mutants affected in farnesyl diphosphate synthetase. AB - Two yeast mutant strains auxotrophic for ergosterol and blocked in farnesyl diphosphate synthetase (EC 2.5.1.1) were isolated. Genetic analysis has shown that these mutant strains carry additional mutations in the ergosterol pathway besides erg20-1 and erg20-2 which affect FPP synthetase. The novel feature of these mutants is their ability to excrete prenyl alcohols (farnesol and geraniol). As geraniol is toxic for yeast cells, the above leaky mutations in FPP synthetase have to be associated with others in the sterol pathway, in order to slow down geraniol synthesis. PMID- 2245474 TI - The identification of mutations in Aspergillus nidulans that lead to increased levels of ADHII. AB - There are at least three alcohol dehydrogenases in Aspergillus nidulans. ADHII has been observed in polyacrylamide gels stained for ADH activity but, unlike ADHI and ADHIII, no physiological function has been attributed to it. This paper describes mutations that have been isolated from strains carrying a deletion in the structural gene for ADHI (alcA) and its adjacent positively-acting regulatory gene (alcR) that restore some ability to utilise ethanol as a carbon source. The mutations map at three loci, and all show elevated levels of the ADHII staining band. An assay for ADHII has been developed. The growth on ethanol has been shown to be dependent on the previously identified aldehyde dehydrogenase (structural gene, aldA). Two of the mutations, alcD and alcE, represent newly discovered mutations affecting ethanol utilisation, while the third mutation is in amdA, a previously described trans-acting regulatory protein. PMID- 2245475 TI - Expression of the avian gag-myc oncogene in Saccharomyces cerevisiae. AB - The gag-myc oncogenic sequence of the avian retrovirus MC29 was first inserted in a multicopy expression vector allowing its expression in Saccharomyces cerevisiae. The oncogene transcripts were detected in yeast by Northern blot hybridization and gag-myc proteins were revealed by immunoprecipitation. On solid medium, the average size of gag-myc transformant colonies was smaller than control. In liquid cultures, the gag-myc strains had a doubling time of 4.7 h compared with 3.1 h in the controls. In one of the recipient strains, and after an initial transient period of 5 days, the gag-myc transformants became physiologically indistinguishable from control. In another recipient strain, the slow-growth phenotype is permanent. Plasmid instability is increased in gag-myc transformants. When a single copy of the gag-myc gene was inserted in a yeast chromosome, no phenotype was observed, showing that slow growth is the consequence of plasmid loss. PMID- 2245476 TI - The development of a heterologous transformation system for the cellulolytic fungus Trichoderma reesei based on a pyrG-negative mutant strain. AB - Six uridine auxotroph mutants of Trichoderma reesei QM 9414 were isolated by resistance to 5-fluoroorotic acid and one strain was identified as OMP decarboxylase negative (pyr-) by a radiometric enzyme assay. Transformation to uridine prototrophy was achieved with the pyr4 gene of Neurospora crassa (up to 1500 transformants/micrograms) and with pyrA of Aspergillus niger (700-800 transformants/micrograms). In many transformants the PYR+ function seems to be present as extrachromosomal DNA. There is evidence for a correlation between the stability of transformants and integration of the vector in the genome whereas unstable transformants are obtained when autonomous replication of the plasmid occurs. PMID- 2245477 TI - Killer toxin production in Pichia acaciae is associated with linear DNA plasmids. AB - We have identified a strain of the yeast Pichia acaciae which produces a "killer" toxin active against the yeast Debaryomyces tamarii. The killer phenotype was associated with the presence of two DNA plasmids, pPacl-1 (13.6 kilobase pairs) and pPacl-2 (7.3 kilobase pairs). P. acaciae strains, cured of these plasmids by irradiation with ultraviolet light, lacked killer activity and were sensitive to toxin produced by the parental strain. A partially cured strain, GS-1215, missing only the smaller plasmid, pPacl-2, also exhibited loss of both toxin activity and immunity. Exonuclease studies revealed that both plasmids were linear double stranded DNA molecules with 5' protected ends. The P. acaciae system differs from that of the well-studied Kluyveromyces lactis "killer" system both in the range of susceptible strains and in the sizes of the plasmids involved. Our studies contradict previous reports that Pichia killer systems are invariably chromosomal. PMID- 2245479 TI - [Utilization of psychiatric care]. AB - The paper is an introduction to a series of articles summarizing hitherto assembled results in the research task P 12-335-806 DU 05 "Reflection of the biopsychosocial background of mental disorders on the consumption of health care" and deals with the first stage 01 "Improvement of the psychiatric information system". It gives an outline of the development of the psychiatric information system in Czechoslovakia, an account of the shortcomings of its present state and proposals for its improvement based on an automated psychiatric case register. PMID- 2245478 TI - A broad bean mitochondrial atp6 gene with an unusually simple, non-conserved 5' region. AB - A nucleotide sequence of broad bean mitochondrial DNA (mtDNA) that contains an atp6 gene of 876 ntp is presented. Relative to other plant atp6 genes, this broad bean gene comprises a 90 ntp non-conserved 5' region, a 759 ntp highly conserved central region and a 27 ntp non-conserved 3' region. The non-conserved, 5' region of the broad bean atp6 gene differs from the corresponding regions of most other plant atp6 genes in that it contains only one potential translation initiation codon and, following this codon, a 63 ntp segment that predicts an amino acid sequence with a predominance of alternating leucines. PMID- 2245480 TI - [Eglonyl in the treatment of schizoaffective psychoses]. AB - The author investigated in an open clinical study the neuroleptic and antidepressive action of Eglonyl in 17 patients who met the criteria (diagnosis of psychoaffective psychosis, symptoms in the sphere of schizophrenia, depressive pathic moods). Eglonyl was administered by injection during the first four days and in tablet form on the subsequent 24 days in individual daily doses of 300-800 mg. At the onset and after 7-day intervals the patients were followed up, by clinical and psychiatric tests, along with the evaluation of the therapeutic effect by means of the clinical global impression scale, CGI, by the BPRS scale, and side-effects by means of the SARS scale. For statistical analysis Wilcoxon's test was used. The expected neuroleptic and antidepressive action of Eglonyl was confirmed in the clinical trials in patients with schizoaffective psychosis- depressive type: marked improvement was recorded in 58.9% of patients, medium improvement in 29.4% and slight improvement in 11.7% of patients. The decline of the global score in BPRS is highly significant (T1 - Tpop = 76.5, P less than 1%). PMID- 2245481 TI - [Problems of siblings of schizophrenics]. AB - In the introduction the authors mention the best known authors who investigated the dynamics of interpersonal relations in families with a schizophrenic patient. The illustrative statement of an intelligent loving sister is adopted from article by Brodoff and according to the authors it has transcultural validity. In our country the solution is only modified by socioeconomic dependence of the adolescent and young adult on the nuclear family. Therefore the separation of the healthy sibling takes frequently an inopportune course and should be adjusted by psychological psychiatric intervention within primary prevention. In the conclusion the authors inform on the psychosomatic reaction of mothers after the establishment of the diagnosis of schizophrenia. A total of seven mothers, sick adolescent (four times a son, three times a daughter). In all instances severe prolonged metrorrhagia was involved. According to catamnestic data four times hysterectomy was performed (always without a pathological finding). PMID- 2245482 TI - [Phalloplethysmographic reaction of optical stimulation in men with erectile disorders]. AB - Using the phalloplethysmographic test, comprising 50 coloured slides of six categories, 50 men with impaired erectivity and a control group of 50 men free from disorders or complaints as regards sexual life were examined. On exposure of slides of heterosexual partner activities positive reactions were recorded in all examined men. Men with impaired erectivity, however, displayed in response to these optic erotic stimuli a lower vasomotor reactivity. These men reacted more frequently positively also to homosexual stimuli and to children. In two men with erectile dysfunction the phalloplethysmographic examination revealed a bisexual orientation, in one a preference of heterosexual child objects, in another eight a quite undefined age differentiation in heterosexual objects. PMID- 2245483 TI - [The effect of marital relations of the parents on the level of general adaptation in sexual offenders]. AB - The authors seek in a group of 297 treated sexual delinquents differences between the group of patients perceiving the relationship of their parents during childhood as harmonious and the group of those who consider it disharmonious. The assembled results are unequivocally to the disadvantage of patients of the second group. The authors found the most marked differences in the sphere of basic psychiatric characteristics (higher number of patients with psychiatric heredity, suicides in the family, alcoholism), characteristics of the initial family (higher incidence of fathers and mothers who were alcoholics, convicted fathers patients with abnormal relations with parents and siblings, spending part of the childhood without the family) and in the sphere of social adaptation (more frequently incomplete basic education, no skilled training, more frequent absenteeism and fluctuations at work). In the sphere of adaptation to partnership and as regards forensic sexological characteristics, there was a less significant, nevertheless convincing, trend shifting the patients from disharmonious families in a direction unfavourable for them. According to the authors' view it may be assumed that these findings are consistent with similar results in other groups of subjects with social problems and that they may be rather associated with a generally criminogenic influence of dysfunctional nuclear families in the delinquent population. PMID- 2245484 TI - [Results of ambulatory care of 103 patients who committed sex offenses]. AB - 103 sexual delinquents were treated in our sexological outpatient clinic. These men were referred for compulsory treatment by courts on account of: indecent exposure (N = 51, i.e. 49.5%), heterosexual aggression (N = 22, i.e. 21.3%), homosexual offence with minors (N = 18, i.e. 17.5%), hetero-sexual paedophilia (N = 8, i.e. 7.8%), fetishist offence (N = 2, i.e. 1.9%), incest with adolescent daughter (N = 1) and zoophilia (N = 1). Sexological treatment consisted of psychotherapeutic, sociotherapeutic and drug treatment. After a three-year follow up the results were evaluated as favourable in 44 men (i.e. 42.7%). 33 men (i.e. 32.1%) relapsed and committed a further sexual crime. 26 men (i.e. 25.2%) remain in a long-term medical care, as favourable sexual adaptation was not achieved in these cases within three years of treatment. Psychological, psychosexual and social characteristics of patients are analysed in connection with results of sexological treatment. PMID- 2245485 TI - [Psychiatric problems in patients from Arab countries]. AB - In 1979-1988 at the Prague Psychiatric Clinic 26 patients from Arab areas were hospitalized. The reason for admission were acute mental disorders involving paranoid, paranoid hallucinatory, manic or depressive syndromes, alcoholism and aggressive behaviour. No bizarre or at least remote psychopathological symptoms were recorded. The author draws attention to the frequent incidence of alcoholism and aggressiveness: these manifestations are at variance with traditions of Arab morality. In the diagnostic evaluation syndromological conclusions proved more useful than nosological ones. PMID- 2245486 TI - [Suicidal ingestion of thioridazine as a cause of severe impairment of heart rhythm--polymorphic ventricular tachycardia]. AB - A 35-year-old female alcohol addicted ingested with suicidal intentions a single dose of 500 mg thioridazine. The course of intoxication was complicated by the development of polymorphous ventricular tachycardia of the torsade de pointes type, about six hours after ingestion. The dysrhythmia was immediately suppressed by stimulation from the right atrium. After 36 hours the stimulation could be abolished. Because of delirium tremens the patient with a normal ECG tracing was returned to the psychiatric clinic. PMID- 2245487 TI - Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. AB - By a sensitive and quantitative fluorometric assay, brain and plasma time dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM. PMID- 2245488 TI - Studies on the myelosuppressive activity of doxorubicin entrapped in liposomes. AB - The myelosuppressive activity of doxorubicin encapsulated in liposomes of differing lipid composition and size was quantified in mice by measurement of changes in spleen weight, peripheral white blood cells (WBC), and bone marrow nucleated cells. Following i.v. administration of free doxorubicin at a dose of 20 mg/kg, a 90% reduction in marrow cellularity was observed on day 3. The marrow nucleated cell count was similar to control values by day 7. Administration of an equivalent dose of doxorubicin that was encapsulated in large (diameter, approximately 1.0 microns) egg phosphatidylcholine/cholesterol (EPC/Chol)(molar ratio, 55:45) liposomes induced an 80% reduction in bone marrow cellularity that lasted for periods of greater than 7 days. Similar results were obtained following administration of large (1.0 microns) liposomal doxorubicin systems formulated with distearoylphosphatidylcholine/cholesterol (DSPC/Chol) (molar ratio 55:45). In contrast, liposomal doxorubicin prepared using small (diameter, approximately 0.1 micron) DSPC/Chol liposomes induced only a 40% reduction (day 3) in bone marrow cellularity, which returned to control values by day 7. Other indicators of doxorubicin-mediated myelosuppressive activity (spleen weight loss and peripheral leukopenia) correlated well with changes observed in marrow cellularity. An exception to this, however, was observed in animals treated with small (0.1 -micron) DSPC/Chol Liposomal doxorubicin, which displayed peripheral leukopenia for periods of greater than 14 days. This extended leukopenia was not observed following administration of small (0.1 -micron) EPC/Chol liposomal doxorubicin. Marrow-associated liposomal lipid and doxorubicin were quantified to determine if the extent of doxorubicin-mediated myeloid toxicity could be correlated to changes in biodistribution of the entrapped drug. It was demonstrated that 10-20 times more doxorubicin is delivered to the bone marrow when the drug is given encapsulated in large liposomes than when it is associated with small liposomes. These data are useful in defining characteristics of liposomal preparations that modulate the myelosuppressive behaviour of entrapped antineoplastic agents. PMID- 2245489 TI - Prediction of ACNU plasma concentration-time profiles in humans by animal scale up. AB - Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2 methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Log-log plots of body weight (W; kg) vs total plasma clearance (CLtot,p; ml/min) and steady-state distribution volume (Vd,ss; l) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was greater than 97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CLtot,p = 50.6 W0.957; Vd, ss = 1.29 W1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CLutot,p and Vd,uss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CLutot,p = 71.7 W0.891; Vd,uss = 1.82 W0.966) were also high (r greater than or equal to 0.991). The extrapolated values vs those observed in a 70-kg human were the following: CLutot,p, 3,160 vs 2,290 ml/min; Vd,uss, 110 vs 106 l. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation. PMID- 2245490 TI - Flavone acetic acid and plasma protein binding. AB - Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA to plasma protein was significantly greater in both healthy human and cancer patient plasma than in mouse plasma. Plasma from patients with cancer bound on the average less FAA than did healthy patient plasma. The concentration of albumin in the plasma varied between healthy humans, cancer patients, and mice, being 5.3 +/- 0.7, 4.7 +/- 0.8, and 3.9 +/- 0.3 g/100 ml, respectively. The protein binding of FAA was found to be dependent on the plasma albumin concentration, but albumin concentration alone was not adequate for the accurate prediction of the percentage of FAA protein bound. Scatchard plots indicated that healthy human plasma had a greater number of high-affinity binding sites than did mouse plasma. FAA binds at the indolebenzodiazepine binding area on albumin and can be displaced from this site by salicylic acid and clofibric acid, but only at supratherapeutic concentrations. Our results indicate that alterations in plasma albumin could contribute to a variable effect with FAA. Therefore, the influence of serum albumin concentration and the nonlinearity of FAA protein binding should be considered in assessment of the appropriateness of a dose schedule for FAA. PMID- 2245491 TI - Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. AB - As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial. PMID- 2245492 TI - A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix. AB - A total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic deaths. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone. PMID- 2245493 TI - Pharmacokinetics of cisplatin given at a daily low dose as a radiosensitiser. AB - A total of 25 patients with inoperable cervical cancer were treated by daily radiotherapy (2 Gy); sensitisation was obtained by administration of 5 mg cisplatin 30 min before each irradiation session. The total cumulative dose of cisplatin varied between 50 and 150 mg. A complete kinetic profile (0-24 h) of platinum (Pt) was established after the first dose and at the end of treatment for 22 patients. Pt was quantified by atomic absorption spectrophotometry using Zeeman-effect background correction for trace analysis. The total Pt AUC0-24h increased from 1.53 +/- 0.77 to 7 +/- 3.55 micrograms.h.ml-1 between the start and the end of treatment (P less than 0.001). Ultrafilterable Pt (Pt UF) rose from 0.079 +/- 0.038 to 0.138 +/- 0.095 microgram.h.ml-1 (P less than 0.01). Elimination half-lives were unchanged for total Pt but rose for Pt UF; these kinetic modifications in Pt UF did not correlate with any significant change in individual serum creatinine levels. No clear correlation was found between the cumulative cisplatin dose and tumor levels measured in 13 patients, and the tumor cisplatin dose did not correlate with response to treatment. Patients with hematological toxicity were characterised by an increase in their residual Pt UF level during treatment. Overall, our findings strengthen the notion of Pt UF kinetic variability during repeated treatment. PMID- 2245494 TI - Biochemical interactions between methotrexate and 1-beta-D arabinofuranosylcytosine in hematopoietic cells of children: a Pediatric Oncology Group study. AB - Children with acute lymphocytic leukemia (ALL) in remission were treated with overlapping sequential infusions of methotrexate (MTX) and 1-beta-D arabinofuranosylcytosine (araC) as part of continuation therapy. The doses and the sequence were chosen to mimic conditions that produced greater than additive antineoplastic activity with these two drugs in preclinical studies. To assess the potential for the drug combination to exhibit greater than additive effect in vivo, we investigated several biochemical parameters that had been associated with synergism in vitro. Because the patients were in remission, the intracellular parameters could only be measured in cytologically normal hematopoietic cells. We observed that (1) the mean plasma concentrations of MTX and araC were above those required to obtain a greater than additive cytotoxicity with the two drugs in tissue culture; (2) MTX did not have a significant antipurine effect in bone marrow mononuclear cells; (3) the mean intracellular concentration of deoxycytidine triphosphate (dCTP) was significantly lower after treatment with the drug combination than after therapy with araC alone; and (4) the ratio of araC triphosphate (araCTP) to dCTP was 2.6 times higher after treatment with the combination than after araC alone. These results indicate that it is possible to achieve in patients the biochemical conditions associated with the greater than additive antineoplastic activity of MTX and araC in vitro. PMID- 2245495 TI - Cerebellar toxicity during cytarabine therapy associated with renal insufficiency. AB - Acute cerebellar toxicity with ataxia and dysarthria is a well-known side effect during high-dose cytarabine therapy. Dose, age, previous neurological disorders, hepatic dysfunction, and renal insufficiency have been inconsistently reported as risk factors. The present paper presents a patient with renal insufficiency who developed severe cerebellar toxicity following treatment with a dose of cytarabine (8 g/m2 over 5 days) not generally expected to be associated with neurotoxicity. Together with a review of the literature, the present case gives evidence of renal insufficiency as a major risk factor in the development of cerebellar toxicity during cytarabine therapy. Reduced doses of cytarabine should be considered in patients with renal impairment. PMID- 2245496 TI - L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. AB - Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits. PMID- 2245497 TI - Baroreflex control of renal sympathetic nerve activity is potentiated at early phase of two-kidney, one-clip Goldblatt hypertension in conscious rabbits. AB - Conscious normotensive and two-kidney, one-clip Goldblatt hypertensive rabbits were studied to determine the sensitivity of the arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate. The relations of the mean arterial pressure-RSNA and mean arterial pressure-heart rate were examined over a wide range of blood pressures produced by infusions of phenylephrine and nitroglycerin. The maximum slope obtained by logistic function analysis was considered to represent the baroreflex sensitivity. In the early hypertensive group (n = 8; mean arterial pressure +/- SEM, 88 +/- 2 mm Hg) on day 5 after renal clip application, the maximum slope of the mean arterial pressure-RSNA relation was -11.3 +/- 1.2, which was significantly greater than that of the sham normotensive group (-6.9 +/- 0.3, p less than 0.05). The maximum slope (-4.3 +/- 0.2) of the mean arterial pressure-RSNA relation in the late hypertensive group (n = 8; mean arterial pressure, 96 +/- 3 mm Hg) on day 21 after renal clipping was significantly smaller than that of another sham group (-7.2 +/- 0.2, p less than 0.05). In contrast to these changes in the baroreflex control of RSNA, the control of heart rate was attenuated according to the magnitude of mean arterial pressure. To elucidate the mechanisms underlying the potentiated baroreflex, the effects of endogenous neuropeptides were investigated. First, plasma concentrations of angiotensin II and arginine vasopressin that are known to affect the baroreflex were determined. Plasma concentrations of vasopressin (3.1 +/- 0.6 pg/ml) as well as of angiotensin II (34 +/- 7 pg/ml) were increased in the early hypertensive group, and the plasma vasopressin returned to a similar level to the sham group in the late hypertensive group (1.3 +/- 0.4 pg/ml). Second, to study endogenous effects of these neuropeptides on the baroreflex, the maximum slopes of the baroreflex curves during infusions of antagonists for the peptides were determined in the early hypertensive group. The maximum slope of mean arterial pressure-RSNA during intravertebral arterial [Sar1, Ala8] angiotensin II (-16.4 +/- 1.5) was significantly greater (p less than 0.05), whereas the maximum slope during intravertebral arterial infusion of d(CH2)5Tyr(Me)arginine vasopressin (-4.7 +/- 0.5) was significantly smaller (p less than 0.05) than that during vehicle infusion (-11.3 +/- 1.2).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245498 TI - Vasoactive intestinal polypeptide facilitates atrioventricular nodal conduction and shortens atrial and ventricular refractory periods in conscious and anesthetized dogs. AB - Our study was designed to determine the cardiac electrophysiological influence of vasoactive intestinal polypeptide (VIP) in conscious dogs. Dogs (n = 8) were chronically instrumented with arterial and venous catheters, cervical vagal cooling coils, and right atrial and right ventricular bipolar epicardial pacing and recording electrodes. After autonomic blockade (10 mg/kg i.v. hexamethonium, 0.11 mg/kg i.v. atropine, and vagal cold blockade), VIP (50 and 100 pmol/kg/min i.v.) or isoproterenol (ISO) (250 and 500 pmol/kg/min i.v.) increased heart rate (maximum increases: VIP, 81.1 +/- 4.2 beats/min; ISO, 61.3 +/- 8.5 beats/min), decreased the atrial-ventricular interval (during constant atrial pacing) (VIP, 41.9 +/- 6.3 msec; ISO, -34.6 +/- 7.4 msec), shortened the atrial effective refractory period (VIP, -24.4 +/- 2.1 msec; ISO, -30.6 +/- 4.4 msec) and ventricular effective refractory period (VIP, -4.2 +/- 0.7 msec; ISO, -10.0 +/- 2.4 msec), and decreased mean arterial pressure (VIP, -51.9 +/- 4.0 mm Hg; ISO, 26.1 +/- 2.4 mm Hg). beta-Adrenergic blockade with propranolol (1 mg/kg i.v.) eliminated the positive chronotropic and atrioventricular nodal dromotropic responses to bolus doses of ISO (30, 100, 300, and 1,000 pmol/kg i.v.) but did not affect the responses to VIP (10, 30, 100, and 300 pmol/kg i.v.). Comparable blood pressure decreases produced by sodium nitroprusside caused only minimal changes in heart rate, atrial-ventricular conduction times, and atrial and ventricular refractory periods. In three additional anesthetized dogs, after vagotomy and beta-adrenergic blockade (1 mg/kg i.v. propranolol), VIP (100 pmol/kg/min i.v.) shortened the atrial-His interval but did not alter intra atrial, intraventricular, or His-Purkinje conduction. Our findings combined with the demonstration by others of VIP-immunoreactive nerves innervating canine sinus nodal cells, atrioventricular nodal cells, and atrial and ventricular myocardial cells suggest that endogenous VIP may directly alter the electrical properties of the heart. PMID- 2245499 TI - Mono-L-arginine-containing compounds dilate piglet pial arterioles via an endothelium-derived relaxing factor-like substance. AB - We determined the effects of mono-L-arginine-containing compounds on pial arterioles of anesthetized piglets. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. Diameter was determined during application of artificial cerebrospinal fluid containing no drugs and during application of 10(-5), 10(-4), 10(-3), and 10(-2) M L-arginine (ARG), L-arginine ethyl ester (AEE), N alpha-benzoyl-L-arginine (NBA), N alpha-benzoyl-L-arginine ester ethyl (BAEE), and L-citrulline (CIT). Initial diameters were 100-200 microns. All of these compounds dilated arterioles, but the threshold concentration needed to elicit dilation varied: 10( 5) M for NBA (n = 5), 10(-3) M for AEE (n = 9) and BAEE (n = 6), and 10(-2) M for ARG (n = 6) and CIT (n = 4). Maximal responses were 15 +/- 8% for CIT, 17 +/- 4% for ARG, 19 +/- 8% for BAEE, 28 +/- 5% for NBA, and 27 +/- 6% for AEE. Indomethacin pretreatment (5 mg/kg i.v.) did not change arteriolar responses to AEE, NBA, and BAEE. However, coadministration of methylene blue (0.5 x 10(-4) M or 0.5 x 10(-3) M) abolished dilation to 10(-3) M AEE or BAEE and attenuated dilation to 10(-5) M NBA. In addition, coadministration of hemoglobin (0.4 x 10( 4) M) abolished dilation to AEE, BAEE, or NBA. Last, intravenous (5 mg/kg) and coadministration (10(-3) M) of NG-methyl-L-arginine blocked dilation to NBA or AEE. We conclude that mono-L-arginine-containing compounds produce pial arteriolar dilation in piglets, possibly involving an endothelium-derived relaxing factor. PMID- 2245500 TI - Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster. AB - The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology. PMID- 2245501 TI - Prostaglandins contribute to activation of baroreceptors in rabbits. Possible paracrine influence of endothelium. AB - The purpose of this study was to test the hypothesis that prostaglandins released from vascular endothelial cells contribute to activation of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in rabbits anesthetized with chloralose. Baroreceptor activity was measured during ramp or step increases in nonpulsatile carotid sinus pressure over a range of 0-175 mm Hg. Exposure of the isolated carotid sinus to inhibitors of prostaglandin formation (indomethacin [n = 10] or aspirin [n = 6]) decreased baroreceptor activity significantly (p less than 0.05). The slope of the pressure-activity relation averaged 0.80 +/- 0.07 %/mm Hg (mean +/- SEM) during control measurements and 0.72 +/- 0.06 and 0.63 +/- 0.05 %/mm Hg during exposure to 10 and 20 microM indomethacin, respectively. Exposure of the carotid sinus to exogenous prostacyclin (PGI2 [n = 11]) increased baroreceptor activity significantly. The slope of the pressure-activity relation averaged 0.89 +/- 0.10, 1.09 +/- 0.09, and 1.26 +/- 0.16 %/mm Hg during control and during exposure to 10 and 20 microM PGI2, respectively. Activity returned to control after removal of PGI2 (0.89 +/- 0.12 %/mm Hg). Removal of endothelium with either a balloon catheter (n = 4) or a jet of a 95% O2-5% CO2 gas mixture (n = 6) decreased the slope of the pressure-activity relation from 0.92 +/- 0.09 to 0.56 +/- 0.08 %/mm Hg (p less than 0.05). Exposure of the denuded sinus to exogenous PGI2 (20 microM [n = 4]) restored activity (slope = 1.09 +/- 0.24 %/mm Hg). Neither indomethacin (n = 5) nor PGI2 (n = 5) nor denudation (n = 5) significantly altered the pressure-diameter relation of the carotid sinus (sonomicrometers), suggesting that the effects on baroreceptor discharge are not caused by altered stretch of the carotid sinus at a given pressure. The results suggest that prostaglandins (e.g., PGI2) released from endothelium contribute in a paracrine manner to activation of baroreceptors during increases in arterial pressure. PMID- 2245502 TI - Intrathoracic current flow during transthoracic defibrillation in dogs. Transcardiac current fraction. AB - To achieve transcardiac threshold current during transthoracic defibrillation, a considerably larger current must be delivered to the thorax to compensate for the shunting effect of the lungs, the thoracic cage, and other elements of the torso. This shunting effect is thus an important determinant of transthoracic defibrillation threshold and can be quantified by the transcardiac current fraction (FC, the ratio of transcardiac to transthoracic threshold currents). Previous estimates of FC have ranged from as low as 3% to as high as 45%. The purpose of of this study was to quantify both FC and the major intrathoracic current pathways. Transthoracic and intrathoracic voltages and currents were simultaneously measured during high-voltage transthoracic shocks in 20 dogs. With correction factors determined from another set of 12 dogs, these raw data were corrected to compensate for field distortion caused by the presence of the intrathoracic electrodes, and the adjusted data were fit to a resistive network model. The results showed that 82% of the transthoracic current was shunted by the thoracic cage, while 14% was shunted by the lungs. The remaining 4% (FC) is the portion that passed through the heart. There was good agreement between the two independent methods used to calculate FC. Analysis based on the model indicated that FC was 3.7%, whereas FC determined by direct measurement with calibrated electrodes was 4.2%. Therefore, the results of this study, in contrast to earlier estimates of FC, show that defibrillation in dogs is achieved by only 4% of the total transthoracic current. PMID- 2245503 TI - Relation between transcardiac and transthoracic current during defibrillation in humans. AB - Conceptually, transthoracic defibrillation threshold current can be considered a function of at least two quantities. It is directly proportional to the transcardiac threshold current and inversely proportional to the transcardiac current fraction (FC) or the ratio of transcardiac and transthoracic current. Although experimental and theoretical estimates of FC have been as high as 45%, previous measurements in humans have not been made. This study was designed to quantify FC in humans. During intraoperative testing of the automatic implantable cardioverter defibrillator, transthoracic rescue shocks of 200-400 J were delivered when the device failed to defibrillate. Simultaneous transthoracic voltage (VT) and transcardiac voltage (VC) between two implanted epicardial patch electrodes were measured. The ratio, VC/VT, was 0.04 +/- 0.03 (mean +/- SD) in 10 patients. In 16 dogs, a comparison was made between direct measurement of FC and VC/VT. FC was determined with a specially designed electrode system, which was calibrated to account for field distortion introduced by the electrodes. There was no significant difference between FC and VC/VT, which were both approximately 0.05, suggesting that VC/VT was statistically equivalent to FC. The results of this study, therefore, indicate that during transthoracic defibrillation in humans, approximately 4% of transthoracic current traverses the heart. This relatively small percentage of current results from the existence of parallel pathways, such as the thoracic cage and lungs, which shunt current around the heart. PMID- 2245504 TI - Ellipsoidal shell subtraction model of right ventricular volume. Comparison with regional free wall dimensions as indexes of right ventricular function. AB - Pulse-transit sonomicrometry was used to measure the base-apex (a), anteroposterior (b), and septal-free wall (c) diameters of the left ventricle and the septal-free wall diameter of the right ventricle (d) in eight excised and three isolated, pump-perfused canine heart preparations, as well as in nine conscious dogs. In the three perfused hearts and in four of the excised hearts, right ventricular free wall regional segment lengths and segment area also were assessed. Biventricular volumes were measured directly with intracavitary balloons in all isolated hearts. When left ventricular balloon volume was held constant, relations between right ventricular free wall dimensions and right ventricular balloon volume were highly linear. With increments in left ventricular volume, however, these relations remained linear but shifted progressively upward, indicating an independent relation between right ventricular free wall dimensions and left ventricular cavitary volume. An ellipsoidal shell subtraction model (pi/6.abd minus right ventricular free wall volume) was developed to estimate right ventricular cavitary volume from cardiac dimensions. With this method, a highly linear relation was observed between calculated right ventricular volume and right ventricular balloon volume (mean r = 0.99 +/- 0.01). Moreover, this relation appeared to be independent of changes in left ventricular balloon volume. With the shell subtraction model, dynamic right ventricular volume was computed in nine conscious dogs, and in four, stroke volume derived from dimensions was compared with right ventricular stroke volume measured with ultrasonic flow probes. A highly linear relation was observed, suggesting the accuracy of the shell subtraction method in vivo. Right ventricular end-systolic pressure-volume and stroke work/end-diastolic volume relations then were evaluated, and both proved to be highly linear in the right ventricle (both mean r = 0.99 +/- 0.01). Thus, the shell subtraction model allows a simple estimate of dynamic right ventricular volume in the intact heart and facilitates assessment of right ventricular performance in vivo. PMID- 2245505 TI - Enhanced chemiluminescence as a measure of oxygen-derived free radical generation during ischemia and reperfusion. AB - It has been suggested that oxygen-derived free radicals may contribute to the myocardial injury associated with ischemia and reperfusion. As the presence of enhanced free radical generation is a prerequisite for such damage, several techniques have been used to provide evidence of increased oxygen free radical production during reperfusion; however, all such techniques have substantial limitations. In this study, we used enhanced chemiluminescence to evaluate oxygen free radical generation during ischemia and reperfusion in the isolated Langendorff-perfused rat heart. The chemiluminescent technique, which has high sensitivity and can monitor radical generation continuously, avoids some of the limitations of earlier methods. Chemiluminescence (expressed as counts per second) decreased from 219 +/- 11 at baseline to 142 +/- 9 during ischemia and markedly increased to a peak of 476 +/- 36 during the first 3-5 minutes of reperfusion. This was followed by a slow decline over 11-16 minutes to a steady state level of 253 +/- 14 (each sequential change in chemiluminescence was highly significant; p less than 0.001). Superoxide dismutase (2,000 units/min) significantly decreased peak reperfusion chemiluminescence to 316 +/- 17 (p less than 0.01). Hearts subjected to a second period of ischemia and reperfusion had a higher peak chemiluminescence (626 +/- 62), which also was significantly attenuated by 1,000 units/min superoxide dismutase (398 +/- 16; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245506 TI - Role of the area postrema in the modulation of the baroreflex control of heart rate by angiotensin II. AB - During angiotensin II (Ang II)-induced elevation of arterial pressure, there is an attenuation of the baroreflex control of heart rate (HR), but the site of this action of Ang II on the baroreflex is not known. To investigate the role of the area postrema, the effects of Ang II on arterial pressure and HR and on the baroreflex control of HR were compared in intact and area postrema-lesioned conscious rabbits. In intact rabbits, infusion of Ang II (2.5-100 ng/kg/min) produced dose-related increases in mean arterial pressure (MAP); the largest dose increased MAP by 32 +/- 3 mm Hg. HR decreased only at the highest dose of Ang II (21 +/- 6 beats/min). In lesioned rabbits, the increase in MAP was reduced (23 +/ 2 mm Hg, p less than 0.05) while the decrease in HR was enhanced (50 +/- 8 beats/min, p less than 0.01). The pressor and HR responses to infusion of phenylephrine (PE) (2-20 micrograms/kg/min) were not different between the two groups. In intact rabbits, the slope of the relation between HR and MAP during Ang II infusion was less than that during PE infusion; in lesioned rabbits, the slopes were not significantly different. Responses to bolus injections of Ang II and PE in intact and lesioned rabbits were similar to those obtained in the infusion study. In another series of experiments, cardiac baroreflex responses with or without background infusion of Ang II were obtained by increasing blood pressure with graded infusions of PE (2-20 micrograms/kg/min). In intact rabbits, infusion of Ang II at 10 ng/kg/min shifted the baroreflex to a higher pressure level (resetting) without changing its slope (sensitivity). Background infusion of PE caused comparable increases in blood pressure, but the subsequent baroreflex response was identical to the response without background PE. In lesioned rabbits, background infusion of Ang II did not change the slope, nor did it reset the baroreflex. The effects of Ang II on baroreflex responses during nitroprusside infusions (2-20 micrograms/kg/min) in intact and lesioned rabbits were the same as those observed during the PE infusions. These findings indicate that the attenuation of the baroreflex control of HR by Ang II results from resetting of the cardiac baroreflex and suggest that this effect is mediated via the area postrema. PMID- 2245507 TI - Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia. AB - The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine. PMID- 2245508 TI - Ouabain increases the calcium concentration in intracellular stores involved in stimulus-response coupling in human platelets. AB - The effect of ouabain on Ca2+ homeostasis in human platelets was studied using both quin 2 and chlorotetracycline to monitor changes in cytosolic Ca2+ as well as changes in the amount of Ca2+ accumulated in intracellular storage sites. In resting platelets, ouabain induces a concentration- and time-dependent increase in cytosolic Ca2+ concentration and a marked elevation of Ca2+ in the intracellular stores. The amount of Ca2+ mobilized from these stores upon stimulation with thrombin, as well as thrombin-induced secretion of platelet 5 hydroxytryptamine, was increased after preincubation with the glycoside (3 x 10( 6) M). These data show that ouabain induces an elevation of intracellular Ca2+ levels, most likely mediated via Na(+)-Ca2+ exchange, and that this incremental amount of Ca2+ is accumulated in an intracellular store involved in stimulus response coupling. This may explain the enhanced functional responses of platelets to agonists in the presence of ouabain and suggests a role for Na(+) Ca2+ exchange in Ca2+ homeostasis of the human platelet. PMID- 2245509 TI - The magnetocardiogram as derived from electrocardiographic data. AB - Magnetocardiographic signals, as present outside the thorax and generated by the depolarization process within the ventricles of the human heart, have been computed by using a model that incorporates the uniform double layer as the exclusive primary source. The volume conductor effects are treated by using an inhomogeneous, multicompartmental model of the thorax, based on "tailored" geometry derived from magnetic resonance imaging. The required activation function, specifying the timing of the ventricular depolarization process, was derived from an inverse procedure that uses as input data electric signals measured at the body surface. Next, the magnetic signals from the same subjects were measured. A close correspondence between computed and measured magnetic signals was observed (relative root mean square residual difference of 0.37). These results demonstrate that magnetocardiograms and electrocardiograms have a common basis and that it is unlikely that prominent sources exist that are electrically silent and yet active in the genesis of the magnetic fields associated with the depolarization process of the heart. Moreover, fresh support is implied for the usefulness of the classical uniform double layer as the electrical source model during ventricular depolarization. The contributions of the secondary sources have previously been found to be a major component of the electric signals; they are now also shown to be a major component of the magnetic signals. PMID- 2245510 TI - Nonlinear dynamics of rate-dependent activation in models of single cardiac cells. AB - Recent studies in isolated cardiac tissue preparations have demonstrated the applicability of a one-dimensional difference equation model describing the global behavior of a driven nonpacemaker cell to the understanding of rate dependent cardiac excitation. As a first approximation to providing an ionic basis to complex excitation patterns in cardiac cells, we have compared the predictions of the one-dimensional model with those of numerical simulations using a modified high-dimensional ionic model of the space-clamped myocyte. Stimulus-response ratios were recorded at various stimulus magnitudes, durations, and frequencies. Iteration of the difference equation model reproduced all important features of the ionic model results, including a wide spectrum of stimulus-response locking patterns, period doubling, and irregular (chaotic) dynamics. In addition, in the parameter plane, both models predict that the bifurcation structure of the cardiac cell must change as a function of stimulus duration, because stimulus duration modifies the type of supernormal excitability present at short diastolic interval. We conclude that, to a large extent, the bifurcation structure of the ionic model under repetitive stimulation can be understood by two functions: excitability and action potential duration. The characteristics of these functions depend on the stimulus duration. PMID- 2245511 TI - STZ-induced diabetes in SHR and renovascular hypertensive rats: dissociation between changes in arterial pressure and vascular collagen synthesis. AB - Streptozotocin (STZ)-induced diabetes depresses the rate of vascular collagen synthesis in the spontaneously hypertensive rat (SHR), but it also reduces arterial pressure (SAP) in this strain. We investigated this phenomenon further by comparing the SHR with the renovascular hypertensive (RVH) rat, because diabetes does not affect SAP in the latter model of hypertension. Renovascular hypertension was induced by clipping the left renal artery of Wistar-Kyoto (WKY) rats; sham-operated WKY were included as normotensive controls. Collagen synthesis of arterial tissue in vitro was quantified as prolyl hydroxylase activity and the rate of radioactive proline incorporation into collagen. Arterial collagen synthesis of nondiabetic SHR and RVH animals was elevated compared to that of the nonhypertensive WKY controls. STZ-induced diabetes (8 weeks) reduced SAP of SHR, but had no effect on SAP of either RVH or normotensive WKY rats. However, diabetes significantly depressed vascular collagen synthesis of both SHR and RVH rats, and, less consistently, of the WKY. The results strongly suggest that STZ-induced diabetes in SHR impairs arterial collagen synthesis independent of associated changes in arterial pressure. PMID- 2245512 TI - Streptozotocin-induced diabetes mellitus lowers blood pressure in spontaneously hypertensive rat. AB - There are conflicting reports showing that alloxan or streptozotocin-induced diabetes in rat increases, decreases or does not alter blood pressure. Since hypertension influences organ-specific diabetic complications, this study was designed to examine the effects of streptozotocin-induced diabetes on blood pressure (BP), hemodynamics and heart weight in spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats. In order to control the influence of weight loss on BP affected by diabetes, we have examined the effect of weight loss without diabetes on BP, hemodynamics and heart weight in SHR. Weight loss parallel to that in diabetic SHR was induced in a group of SHR by food restriction (fasting). Significant (P less than .05) decreases in systolic and direct BP were observed in diabetic SHR. This hypotensive effect was accompanied by a significant (P less than .05) decrease in total peripheral resistance, but no change in cardiac output. These blood pressure and hemodynamic findings in diabetic SHR were complimented by a significant (P less than .05) reduction in left ventricular weight to body weight ratio. On the contrary, fasting SHR with weight loss equivalent to that in diabetic SHR showed no change in BP or total peripheral resistance. Further, fasting SHR revealed a significant (P less than .05) increase in heart weight to body weight ratio. The weight loss of equal magnitude induced by streptozotocin-induced diabetes in NWR did not have any effect on BP or hemodynamics. In addition, like fasting SHR, diabetic NWR showed a significant (P less than .05) increase in left ventricular weight to body weight ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245513 TI - Endothelin-induced renal vasoconstriction and increase in cytosolic calcium in renal vascular smooth muscle cells. AB - This study was designed to investigate the effects of the potent vasoconstrictor, endothelin, on renal hemodynamics in rats in vivo, and in addition, to measure intracellular calcium ion ([Ca2+]i) in monolayers of renal vascular smooth muscle cells in culture using the fura-2 method. Endothelin (1 nmol) dramatically decreased renal blood flow from 7.0 +/- 0.5 ml/min to 2.6 +/- 1.0 ml/min, whereas it increased mean arterial pressure from 100 +/- 2 mmHg to 113 +/- 7 mmHg. These alterations persisted over 20 minutes in conscious and almost unrestrained rats. Endothelin (10(-8)-10(-7) mol/l) immediately increased [Ca2+]i, although the increase by endothelin (10(-9) mol/l) was relatively slow. The increase persisted in the presence of 1 mmol/l extracellular calcium. In the absence of extracellular calcium, only a small, transient increase of [Ca2+]i was observed. These results indicate that endothelin produces renal vasoconstriction and increases the [Ca2+]i in cultured renal vascular smooth muscle cells. The latter effect is dependent mainly on extracellular calcium. PMID- 2245514 TI - Effects of endothelin on blood pressure and renal hemodynamics in DOCA-salt hypertensive rats under conscious and unrestrained condition. AB - The acute effects of endothelin, a potent vasoconstrictor peptide, were investigated on renal hemodynamics, blood pressure and heart rate in conscious and unrestrained DOCA-salt hypertensive rats to compare with those in normotensive, sham-operated rats. The plasma concentration of immunoreactive endothelin was measured following the administration of endothelin, 0.4 nmole IV. After a dose of 1 nmole/kg IV, the blood pressure fell transiently and then rose gradually, while the renal blood flow remained decreased throughout the observation period. Both the blood pressure elevation and the renal blood flow decline in DOCA-salt hypertensive rats exceeded that in controls. In both experimental groups the arterial plasma endothelin concentration decreased rapidly after the peak was achieved. The disappearance of endothelin from plasma was significantly delayed in the DOCA-salt hypertensive rats. These findings suggest that the marked increase in blood pressure and the altered renal hemodynamics induced by endothelin in DOCA-salt hypertensive rats are due in part to a decrease in endothelin clearance. PMID- 2245515 TI - Chronic antihypertensive drug treatment decreases protein kinase C activity in platelets from SHR. AB - There is evidence that protein kinase C activity in platelets from adult SHR is significantly higher than this activity in age-matched WKY. In the present study, protein kinase C activity in the SHR was measured following antihypertensive drug treatment. Chronic administration of enalapril to SHR for 2 weeks decreased both systolic blood pressure and protein kinase C activity to the levels seen in the WKY. Similar results were obtained in case of chronic treatment of SHR with hydralazine or nifedipine. These results suggest that enhanced protein kinase C activity of SHR can be suppressed by lowering blood pressure by antihypertensive drugs. PMID- 2245516 TI - Influence of age on the nocturnal fall of blood pressure and its modulation by long-acting calcium antagonists. AB - The clinical significance of the nocturnal fall of blood pressure (BP) was examined. BP was monitored every 5 min for 24 hrs by means of a finger volume oscillometric device. The nocturnal fall was observed in all age groups (young: less than 40, n = 49; adult: 40 less than or equal to less than 60, n = 110; old: 60 less than or equal to, n = 33). The amplitude of nocturnal fall of BP (averaged daytime blood pressure--averaged nighttime blood pressure) in old patients (systolic = 13 +/- 11, diastolic = 10 +/- 8 mmHg, mean +/- SD) was similar to that in the young patients (systolic = 11 +/- 8, diastolic = 10 +/- 8 mmHg). These 192 subjects were also classified according to mean BP level (MBP) averaged for daytime in the ambulatory blood pressure monitoring records [MBP less than 85 (mmHg), n = 31; 85 less than or equal to MBP less than 100, n = 72; 100 less than or equal to MBP less than 115, n = 49; 115 less than or equal to MBP, n = 25]. BP level did not affect the pattern of circadian variation in the normal subjects or in the essential hypertensive patients at WHO stage I or II. The amplitude of the nocturnal fall in systolic BP increased with the increase in BP level, but this was not the case with diastolic BP (mean daytime BP less than 85 mmHg: systolic = 11 +/- 8, diastolic = 8 +/- 6 mmHg; 85 less than or equal to less than 100: systolic = 14 +/- 8, diastolic = 11 +/- 6 mmHg; 100 less than or equal to less than 115: systolic = 17 +/- 9, diastolic = 11 +/- 8; 115 less than or equal to: systolic 17 +/- 8, diastolic = 11 +/- 6 mmHg). Nitrendipine (8.6 +/- 5.6 mg, 22.5 +/- 11.4 days, n = 14) and nisoldipine (9.3 +/- 6.2 mg, 21.5 +/- 11.4 days, n = 15) administered once daily in the morning or nifedipine slow release tablet, 20 mg twice daily (n = 15, 17.7 +/- 5.2 days) induced a significant downward shift in the circadian BP pattern, in other words, the hypotensive effect was also observed during the night when the BP had already been low. Taken together, the information on the nocturnal behavior of BP would be valuable, especially in treating aged patients with essential hypertension with a long-acting antihypertensive drug. PMID- 2245517 TI - A cross-sectional survey of home blood pressure in a rural community in northern Japan. AB - A cross-sectional survey was performed on home blood pressure recordings (home BP) in a rural community in northern Japan. In total, 1190 participants (495 men and 695 women which consist 61.5% of the greater than or equal to 15 year-old regional population, n = 1933) were asked to measure home BP every morning for a month, using a semiautomatic BP measuring device. The actual measurements were done 16.8 +/- 10.2 times (mean +/- SD) for men and 19.0 +/- 9.4 times for women. Home systolic (SBP) and diastolic BP (DBP) was elevated gradually with age in both sexes, although DBP tended to fall after reaching 70 years old in men. SBP and DBP thus measured were significantly lower than those of casual BP of ordinary Japanese people reported by the Ministry of Health and Welfare, Japan, by 11.4 +/- 4.3 mmHg SBP (mean +/- SD) and 5.9 +/- 1.6 mmHg DBP in men, and 12.7 +/- 5.1 mmHg SBP and 8.1 +/- 2.5 mmHg DBP in women. When WHO criteria were applied to the home BP, 2.8% of men and 0.6% of women were considered to be definitely hypertensive, and 7.9% of men and 6.4% of women as of borderline cases, indicating the underestimation of hypertensive population by means of home BP. Based on these data, we demonstrated the values equal to 1SD or 2SDs above the mean in each age group to tentatively determine biological normalcy. It is necessary to define the relationship between home BP and target organ disease or hypertensive complications. A long-term prospective study is also necessary to define the relationship between home BP and long-term morbidity or mortality. PMID- 2245518 TI - Role of the kidney in the pathogenesis of primary hypertension. AB - Primary hypertension in animals and humans probably represents several different pathophysiological states rather than being a uniform nosological entity. Among other factors, renal mechanisms may be primarily and secondarily involved. The availability of genetically homologous animal models for hypertension has greatly promoted studies on the etiology and pathogenesis of high blood pressure disease. In particular, renal transplantation studies between genetically hypertensive and normotensive rats from three different models have provided strong evidence for a primary role of the kidney in genetic hypertension. Other factors, such as vascular, neural, and humoral mechanisms have also been shown to be involved and may be particularly effective in increasing blood pressure, when they act through the kidney. Several functional and biochemical differences have been identified between kidneys from genetically hypertensive and normotensive animals. However, the relative contribution of each of these factors to the development of primary hypertension remains to be determined. Evidence from studies on human renal graft recipients also indicates that, among other factors, the kidney plays an important role in the development of primary hypertension in humans. PMID- 2245519 TI - The role of platelet-activating factor in inflammation. PMID- 2245520 TI - Identification of a low-affinity subset of protamine-reactive IgM antibodies present in normal, deficient in AIDS, sera: implications for HIV latency. AB - We demonstrate here that the protamine-reactive IgM antibodies previously shown to be present in normal adult sera include two subsets differing in binding affinity. The principal, high-affinity subset was detected in AIDS and ARC as well as normal sera. The secondary, low-affinity subset, however, was absent or markedly deficient in AIDS or ARC sera. Protamine-reactive IgM antibodies were also detected in normal pediatric sera, suggesting that one subset of that class of antibodies may be "natural," i.e., not antigenically induced. The proportionate titer of the low-affinity protamine-reactive IgM antibodies was determined for HIV-positive males who were asymptomatic or mildly immune deficient at specimen collection. Of those who subsequently remained AIDS free for 18 months to 7 years, more than 90% had titers in the range established for the normal sera, while of those diagnosed with AIDS or ARC within 12 months, more than 80% had titers below the normal range. We propose that the low-affinity subset of adult sera corresponds to the natural antibodies of pediatric sera and that a relationship of those natural antibodies to resistance to progression of HIV pathogenesis is suggested. PMID- 2245521 TI - Intraglomerular leukocyte recruitment during nephrotoxic serum nephritis in rats. AB - Although circulating phagocytic cells are important mediators of glomerular injury, their recruitment mechanisms are not completely understood. In this study, the intraglomerular trafficking of leukocytes was characterized in a rat model of acute glomerular injury induced by nephrotoxic serum (NTS). Polymorphonuclear (PMN) cells infiltrated, then disappeared rapidly, reaching a peak at 2 hr. By 6 hr the PMN migration had almost reversed but small numbers persisted until Day 7. The monocyte influx began almost simultaneously but was of lesser magnitude. However, the number of ED-1+ monocytes increased progressively from 60 min to reach a plateau by Day 2 and persisted to the end of the study (Day 28). Quantitation of intraglomerular Ia+ cells suggested in situ activation of monocytes within the glomeruli. Increased Ia+ cells were first evident on Day 2. By Day 5, 80% of the intraglomerular macrophages were Ia+. Complement depletion with cobra venom factor abrogated early albuminuria, delayed the initial PMN influx, but failed to attenuate monocyte migration. T lymphocytes appeared briefly between 10 min and 2 hr. In vitro proliferation study failed to demonstrate lymphocyte sensitization to glomerular basement membrane (GBM) antigens. A unique population of cells (OX19 OX8+), possibly representing natural killer cells, was present from Day 1 to Day 14. During the secondary wave of proteinuria (autologous phase), all leukocytes had disappeared except for macrophages and a small number of OX19-, OX8+ cells. A complex intraglomerular migration of leukocytes was triggered by the binding of nephrotoxic antibodies to GBM antigens. We speculate that this cascade involves several cell-to-cell interactions necessary for the full expression of glomerular injury. PMID- 2245522 TI - Diagnostic criteria for Sjogren's syndrome: the state of the art. AB - The diagnostic approach to Sjogren's syndrome (SS) is devoted to the assessment of glandular and extraglandular features of the disorder. Although this syndrome has been attracting growing interest from many investigators in the last few decades, complete agreement on the diagnostic tools to be used for this syndrome has not yet been reached. Finding a rational diagnostic approach to Sjogren's syndrome is even further complicated by the fact that this disease may exist alone, or in association with a number of extraglandular systemic manifestations or a well-defined systemic autoimmune disease. In this paper the entire matter has been critically reviewed in order to evidentiate the differences among the various diagnostic procedures proposed by different authors and to underline the need for a uniform classification criteria for SS. PMID- 2245523 TI - Diagnosis and differential diagnosis of keratoconjunctivitis sicca associated with tear gland degeneration. AB - The clinical tests to diagnose keratoconjunctivitis sicca are weak, whereas the laboratory tests are very powerful, but there is no reason whatsoever to discard the present clinical tests. For example, finding a Schirmer test consistently lower than 5 mm is an easy way to strongly suspect a dry eye state. The level of tear fluid production can help one to determine the preferred viscosity of the tear substitute. Then, what test should be used other than the rose Bengal test to evaluate the over-all effect of the dry eye state on the external eye? What other test than the break-up time is there to evaluate tear film stability? There is no doubt that laboratory tests will be used in the future as routine clinical procedures, in addition to but not replacing the clinical tests, as the tear protein concentration, the Schirmer test values and the break-up time are important for the diagnosis of dry eye and, analyzed together, they may be of value to differentiate between Sjogren's and non-Sjogren's keratoconjunctivitis sicca. PMID- 2245524 TI - Comparison of lupus activity indices. AB - The multiple manifestations of systemic lupus erythematosus recall the ancient Greek monster the Hydra. No one was sure how many heads it had or what they all looked like and severing one head led to the generation of others. Similarly, lupus presents with many different 'faces' and there has been a dearth of agreement about disease indices in SLE. This problem is discussed and the results of two international workshops examining three systems (BILAG, SLAM and SLEDAI) are presented. It is suggested that we may be close to agreeing how many heads the Hydra of lupus has and what they look like. PMID- 2245526 TI - The treatment of lupus in the 1990s. PMID- 2245525 TI - Antibodies to antinuclear subsets in systemic lupus erythematosus and rheumatoid arthritis. AB - In this study, technical, clinical and genetic aspects of anti-Ro/SSA, anti-Sm, and anti-RNP are discussed; different techniques may reveal differences in autoantibody frequencies and associations. Finally, the importance of anti-RA33, a new autoantibody characteristic of rheumatoid arthritis, is evidenced. PMID- 2245527 TI - Hemapheresis in systemic lupus erythematosus. AB - The place of plasma exchange in treating systemic lupus erythematosus remains to be discussed. Currently available clinical data suggest that PE may be a useful additional therapy only in certain subsets of some severe lupus manifestations such as CNS involvement, crescentic glomerulonephritis, and lupus vasculitis. Using PE could also be of interest in certain manifestations of the anti phospholipid syndrome. The conflict between the rapid improvement seen in some biological abnormalities (circulating immune complexes, ds-DNA antibodies) and the lack of obvious parallel clinical benefits remains a field of stimulating investigation. Next to plasma exchange associated with conventional corticosteroid or immunosuppressive therapies, other approaches could be of value such as the synchronization of plasma exchange and cyclophosphamide pulses, or the selective removal of assumed pathogenetic antibodies or immune complexes. Insufficient data are presently available to interpret the results of the former. The latter methods could offer the advantage of more precisely establishing the role of selectively removed substances in the pathogenesis of SLE. PMID- 2245528 TI - Hypothesis: systemic lupus erythematosus as a disease secondary to polyclonal lymphocyte activation. AB - Systemic lupus erythematosus (SLE) is characterized by the concomitance of B cell polyclonal activation and the production of a wide spectrum of autoantibodies showing a marked preference for nuclear antigens. We propose the hypothesis that the production of the most pathogenic antinuclear antibodies with high affinity and IgG isotype is driven by antigens liberated by the death of rapidly proliferating lymphoid cells. The disease could evolve in three steps: (1) polyclonal B cell activation and proliferation caused by unknown etiologic factors (virus?, mitogen? ...); (2) primary activation of natural antibody producing clones leading to the appearance in the serum of large amounts of natural autoantibodies with public idiotype; and (3) secondary immunization against molecules synthesized in large quantities during lymphocyte proliferation, released by dying cells and subsequently presented in an immunogenic form to T cells. These molecules include nucleic acids (DNA, RNA), nucleic acid-binding proteins (histones, Ro, La), and parts of the RNA splicing machinery (RNP). Other autoantibody activities could relate to cross-reactivities or the binding properties of DNA-anti-DNA immune complexes. PMID- 2245529 TI - Cytokines and anticytokines. AB - The inflammation in the rheumatoid synovial membrane may be characterised by the concomitant presence of proinflammatory and anti-inflammatory mechanisms and mediators. These events may be spacially distributed within the tissue and may be visualised as waves of inflammation followed by waves of repair. The aim of therapy must be to enhance the anti-cytokine and reoperative processes over the inflammatory ones. PMID- 2245530 TI - Immunity to heat shock proteins in rheumatoid arthritis. AB - Heat shock proteins (hsp) or "stress proteins" are a group of highly conserved proteins which are important in the day to day function of all cells. Early studies by others have indicated that immunity to the 65 kDa hsp of mycobacteria is important in the development of arthritis in the adjuvant arthritis model in rats. In this paper, we review the evidence suggesting that, as for the rat model, immune reactivity to hsp is of importance in the human disease. Elevated levels of IgG antibodies to the 65 kDa hsp of mycobacteria are characteristic of rheumatoid arthritis (RA) patients. Much of this antibody cross-reacts with human 65 kDa hsp and is therefore autoreactive. The 65 kDa hsp is found in synovial fluid and is therefore a potential target for antibody. Antibodies to the 70 kDa hsp (both of mycobacterial and human origin) are elevated, but not specifically, in RA. Increased T cell responses to the 65 kDa hsp are also found in synovial fluid of RA patients. Although gamma delta T cells are present in the synovial joint of RA patients, they do not appear to be particularly increased in frequency although the subset distribution of these cells is clearly different from that seen in the circulation. In fact, the synovium looks like the "gut" with regard to these subsets! PMID- 2245531 TI - Xerostomia. AB - This communication describes the etiology, frequency, and various symptoms involved in the phenomenon of dry mouth and also discusses in detail the objective tests generally used when evaluating patients for xerostomia as the oral component of Sjogren's syndrome. It is stressed here that no single test has a sufficiently high specificity and sensitivity and consequently we recommend that at least two tests should give abnormal results before the xerostomia diagnosis is accepted. PMID- 2245532 TI - Immunological treatment of rheumatoid arthritis. AB - Till now the therapeutic immunomodulation of rheumatoid arthritis (RA) has been non-specific, using either slow acting drugs which act mainly but not exclusively on macrophages (gold salts) or on T CD4+ cells (D penicillamine), or immunostimulating agents (Levamisole) or immunodepressive drugs which do not affect a specific subpopulation of lymphocytes. Various other therapeutic approaches such as dietic manipulations, steroid pulses and plasmapheresis have been proposed. Methotrexate is a very interesting development in the treatment of RA. However, the results of such treatments on the long term outcome of the disease have been unsatisfactory. Early and associated treatments must be studied. After the interesting experimental results obtained with thoracic duct drainage, a partially specific immunotherapy acting mainly on CD4+ T cells has been developed using cyclosporin A and total lymphoid irradiation. However, a more specific immunotherapy of RA may be considered, using monoclonal or polyclonal anti-HLA class II antibodies or anti-CD4 monoclonal antibodies. Immunomodulating treatments with cytokines or anticytokines, anti-T receptor monoclonal antibodies, anti-idiotypic antibodies, and vaccination with T cell clones or synthetic peptides are possibilities of major interest for the future. PMID- 2245534 TI - 18th Open Scientific Meeting of the Hip Society. Proceedings. PMID- 2245533 TI - IgG and rheumatoid factor at a glance. AB - The presence of rheumatoid factors in both sero-positive and seronegative rheumatoid arthritis patients is well established. Immune complexes are formed through the binding of IgM, IgG or IgA rheumatoid factors to the Fc fragment of IgG. IgG rheumatoid factor is of particular interest in that being both antigen and antibody, it can self-associate to form immune complexes. It has recently been shown that there is a decrease in the galactose content in the Fc oligosaccharides of IgG leading to a vacant pocket where the galactose moiety normally resides. One of the mechanisms through which IgG can potentially self aggregate is by the insertion of galactose of the Fab oligosaccharides of one IgG molecule into the galactose free pocket of a second IgG molecule. PMID- 2245535 TI - Technical aspects of cementless total hip arthroplasty. AB - The technique of cementless total hip arthroplasty (THA) places many demands on the surgeon, who must understand the rationale of the prosthetic design to take full advantage of its features. In addition, the surgeon must be able to gauge the quality of the available bone either by preoperative roentgenographic examination or by intraoperative assessment or both. The surgeon must then choose the prosthesis that will predictably fit the individual conditions. Proper instrumentation, practice in a workshop environment, prophylactic wiring of the femur, and postimplantation testing of the prosthesis are important to achieve lasting results of cementless THA. PMID- 2245536 TI - The biomechanical problems of polyethylene as a bearing surface. AB - The metal backings of acetabular components can reduce the available polyethylene thickness, often to an alarming extent. This study indicated that the pitting and cracking of thin polyethylene surfaces have some similarities to tibial and patellar bearings and that creep-related deformation occurred more frequently in thin polyethylene components. Additionally, it appears that dimensional tolerances of the polyethylene inserts are difficult to maintain and may result in a nonuniform fit of both the femoral head into the component and the component into its own metal backing, which can lead to component separation. It is difficult to accurately measure the changes in material and mechanical properties of polyethylene over time. An additional ramification is that flaws, such as voids in the polyethylene, cannot be attributed to problems of bulk supply, fabrication, or postmanufacturing treatment. Orthopedic device manufacturers should keep samples of each lot of polyethylene used and provide components with serial numbers so that the source, composition, and properties of the original bulk material and material "as fabricated" can be documented. This would permit researchers studying revisions or postmortem samples to determine the changes in the polyethylene over time in vivo, thus improving the understanding of this crucial material. If manufacturers were to include dimensions and tolerances of the polyethylene inserts in their product literature, accurate measurements of wear of retrieved specimens may be possible. PMID- 2245537 TI - Capacitive coupling as an adjunctive treatment for avascular necrosis. AB - The purpose of this study was to determine the effectiveness of capacitive coupling, a noninvasive method for applying electrical stimulation to biologic tissues, when used as an adjunct to decompression and grafting in the treatment of avascular necrosis (AVN) of the femoral head. It also compared the results of core decompression and grafting with nonoperative management. Forty patients with Stages I-III AVN of the femoral head were treated with core decompression and grafting. All wore capacitive coupling units with electrodes placed over the femoral head continuously for six months. One-half of these units were active and one-half were inactive. Patients were followed for two to four years. Results were determined by preoperative and postoperative Harris ratings, quantitative roentgenographic measurements, and the number of hips that required total hip arthroplasty (THA). After all evaluations were completed, patients were divided into stimulated and nonstimulated groups. Patients in both groups were similar regarding gender, etiology, and roentgenographic stage of involvement. Results were also compared to 55 hips previously treated symptomatically, without surgery or electrical stimulation. There were no fractures, infections, or other significant complications in any of the hips operated on. Hips treated with decompression and grafting, both with and without electrical stimulation, were more satisfactory than hips treated symptomatically in regard to roentgenographic progression and the need for THA. There was, however, no indication that the addition of capacitive coupling gave better results than decompression and grafting alone. PMID- 2245538 TI - Osseointegration of titanium implants in total hip arthroplasty. AB - Osseointegration is defined as direct contact on the light microscopic level between living bone tissue and the implant. Using titanium screw dental implants in the jaw, a lasting interface under loaded conditions extending over a 20-year follow-up period has been demonstrated. This demonstration brings up the question whether a similar interface can be achieved in total hip arthroplasty (THA) between living bone and a titanium alloy implant under necessitated conditions of immediate loading. Two series of cases are reported. The first series used a femoral, press-fit, titanium alloy component and the second used a press-fit titanium acetabular component and redesigned femoral, press-fit, titanium alloy component. Both demonstrated a high percentage of good to excellent results. Roentgenograms showed that the geometrical changes in the redesigned femoral component gave early indications of a better fixation with loading in valgus, less subsidence, and less evidence of distal stress transfer. A two-and-one-half year postoperative anatomic specimen study confirmed osseointegration to the press-fit titanium alloy femoral component. Multiple areas of contact between bone and metal without fibrous interposition were seen. Examination by electron microscopy supported the light microscopic findings. These findings support further use of smooth, press-fit titanium components in THAs without the need for porous coating, mesh, or other surface modifications. PMID- 2245539 TI - Femoral stem fixation. The case for cement. PMID- 2245540 TI - Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent. AB - The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process. PMID- 2245541 TI - Bioceramics. Is there a difference? AB - Bioceramics of aluminum oxide and calcium phosphate have a wide range of applications in orthopedic surgery. Each type of bioceramic is substantially different from the other, and variations exist within each type depending on the source and intended application. The physical, mechanical, chemical, and biologic properties are specific to each bioceramic. Significantly different tissue responses have been demonstrated among the various aluminum oxide, hydroxylapatite, and tricalcium phosphate bioceramics. Since the prospects for expanded clinical applications are excellent, the clinical community should become better acquainted with these types of biomaterials. PMID- 2245542 TI - Dislocation after total hip arthroplasty. Causes and prevention. AB - In this prospective study, a technique of positioning the acetabulum by bony landmarks of the pelvis in the standing position was developed using a standing lateral preoperative roentgenogram with the X-ray tube centered over the trochanter. Since 1984, 441 total hip arthroplasties (THAs) were done through the posterior approach with a 1.14% dislocation rate through 1988 and no dislocations in 1989. To prevent impingement and dislocation, it was determined that the safest range for cup position was 30 degrees-50 degrees abduction and 20 degrees 40 degrees flexion from the horizontal. To measure postoperative cup position, a standing true lateral roentgenogram of the operated hip allowed direct measurement of cup flexion and was reproducible within 10 degrees. No special instruments are necessary for this technique, which can be used with any THA system. PMID- 2245543 TI - Cementless total joint arthroplasty prostheses with titanium-alloy articular surfaces. A human retrieval analysis. AB - Surgical implants of titanium alloy (Ti-6Al-4V) have been found to be susceptible to abrasive wear, resulting in the well-known phenomenon of metallosis. In the presence of the acrylic debris generated by loose joint arthroplasty prostheses, this abrasive wear is greatly increased. However, the bone loss seen in these cases has generally been presumed to be due to the osteolytic effects of particulate acrylic, not the alloy debris, which has generally been assumed to be biocompatible. To examine the in vivo effects of titanium-alloy wear without the added presence of acrylic debris, a comprehensive analysis was made of cementless human joint arthroplasty prostheses with Ti-6Al-4V alloy surfaces articulating on ultra-high molecular weight polyethylene (UHMWPE). Specimens, including the prostheses, synovium, pseudocapsule and additional soft tissues, and periarticular bone, were retrieved from 22 hips and two knees. Specimens were examined by histologic techniques, energy-dispersive X-ray analysis, and electron microscopy. Serial sections of the implants were evaluated for tissue ingrowth. Tissues surrounding all joints implanted more than one year showed some degree of discoloration indicative of metallosis, whereas after two years the synovium was hypertrophic and villiform. Histologic evaluation showed good fixation by bony ingrowth in the vast majority of cases, although location and extent of ingrowth was dependent on numerous factors. Viability of ingrowth bone was established by fluorochrome labeling. However, despite good biologic fixation, cavitary osteolysis of the bone surrounding the implants was frequently identified. These lesions were filled with sheets of aggressive macrophages within a matrix of fibrous tissue and necrotic debris. Under polarized light the macrophages were found to be filled with alloy and polyethylene fragments of a characteristic size. Osteoblast-mediated remodeling of bone was infrequently observed. Instead, the bone was resorbed along a front in contact with the granulomatous tissues filling the cystic lesions. Visible burnishing was observed on every articular surface, with a linear relationship between wear and time implanted. By one year the surfaces were covered with a characteristic "scratch and gouge" pattern, similar on all sizes of femoral heads as well as the total knee prostheses. This study demonstrates that the combination of Ti-6Al-4V alloy and UHMWPE, when used as a bearing surface combination in total joint arthroplasty prostheses, results in excessive wear of both metal and polymer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245544 TI - Making core decompression work. AB - Meaningful assessment of a treatment modality for osteonecrosis (ON) must take into account a number of factors: (1) an accurate diagnosis, (2) consistent staging of the disease process, (3) understanding of the variability of the disease, (4) consistent application of the treatment modality (or the surgical technique), and (5) a clear understanding of the goal of the treatment used. This article reviews the important steps of a diagnostic algorithm that has been used to accurately diagnose and stage the disease process of ON. A consistent surgical technique with clearly defined goals is also outlined. The results of two clinical studies that were based on these diagnostic and therapeutic philosophies and that assess the role of core decompression in the treatment of ON are reviewed. The first study compared core decompression to conservative management in a prospective randomized study of 55 hips. Decompression provided more predictable pain relief and changed the indications for further surgical intervention more consistently than did conservative management. The second study represents a preliminary review of a ten-year study of the decompression procedure; it showed that core decompression was particularly useful in Stage I and Stage II ON. Roentgenographic stabilization was most predictable for Stage I hips. Core decompression can be a safe, effective, and predictable procedure in the treatment of Stage I and Stage II ON. PMID- 2245545 TI - The case for revision arthroplasty using antibiotic-loaded acrylic cement. AB - For managing infected joint implants, revision arthroplasty using antibiotic loaded acrylic cement (ALAC) has proven to be superior to other methods of treatment that are currently available. Ablation of the implant, cement, and necrotic tissue is essential. Further refinement of the ALAC method is possible. Analysis of complications shows that disarticulation and a permanent Girdlestone can become rare surgical procedures. PMID- 2245546 TI - The effect of stem stiffness on femoral bone resorption after canine porous coated total hip arthroplasty. AB - Bilateral noncemented total hip arthroplasty (THA) was produced in dogs to determine the effect of stem stiffness on stress-related bone resorption. Two porous-coated femoral implants of substantially different stiffnesses were designed for direct comparison. One was manufactured from cobalt-chromium (CoCr) alloy, the other from titanium alloy. The titanium stem was hollowed out to a wall thickness of 1 mm to further reduce its stiffness. The cumulative stiffness differences were about 5.4-fold axially and 3.6-fold in bending and torsion. Staged bilateral THA was performed on eight dogs. Each dog received a stiff CoCr stem on one side and a flexible titanium stem on the other. After death, the femora were removed and processed for undecalcified thin-section histology. Bone ingrowth and remodeling were quantified by computer-aided image analysis and compared between stem designs. All femoral specimens showed bone ingrowth fixation of both stiff and flexible stems along the implant length. Tetracycline labeling indicated active bone turnover in the femoral cortex and in regions of ingrowth. However, gross differences in femoral bone remodeling were observed both roentgenographically and histologically. Femora with the flexible stems consistently showed much less bone resorption than those with the stiff stems. Quantitative analysis of paired cross-sections indicated an average of 25%-35% more cortical bone area in the femora with flexible stems. Severe resorption of the cortex in the midstem region occurred in three of the femora with the stiff stems but in none with the flexible stems. Stem stiffness strongly influences bone remodeling. The flexible stem results in more uniform load transfer and less stress shielding. PMID- 2245547 TI - Acetabular dysplasia in the adolescent and young adult. AB - Hip dysplasia is a major cause of osteoarthrosis in adults. Early aggressive osteotomy has the potential of preventing the development of arthritis, but carries with it significant risks. The problem is further complicated because the surgeon has no means of quantifying the dysplastic deformity or of predicting what a particular combination of osteotomies would do to correct the deformity. This study describes methods of quantifying hip-joint geometry in three dimensions based on computed tomography and magnetic resonance studies, and of simulating pelvic osteotomy to correct the deformities. The study analyzes 49 normal hip joints and 20 dysplastic hip joints. The results show that the normal acetabulum is nearly a full hemisphere, which is anteverted 20 degrees and abducted 53 degrees. The normal lateral center-edge angle is 37 degrees. The dysplastic acetabulum is not anterolaterally maldirected, as has been assumed, but is globally dysplastic. Analysis of the individual dysplastic hip joints showed a wide variability. Some patients were deficient globally, some anterolaterally, and some posterolaterally. Methods of analyzing a patient's hip joint, quantifying abnormalities, simulating surgery, and predicting results are demonstrated in a case example. PMID- 2245548 TI - Intraoperative dexamethasone irrigation in lumbar microdiskectomy. AB - In 45 lumbar hemilaminectomy/microdiskectomy patients, a control group of 23 patients had the standard operative procedure. The remaining 22 patients were treated with intraoperative irrigation of long-acting dexamethasone before incision closure. Age, weight, gender ratio, mean postoperative hospital stay, mean in-hospital narcotics usage, and incidence of perioperative complications among the two groups were compared. Age and gender ratios were comparable, although the control group was significantly heavier in body weight than the steroid-irrigated group. The steroid-irrigated group had a significant reduction in hospitalization and a marked reduction in narcotics usage compared with the control group. Postoperative fever occurred in one patient in the steroid group. The control group had three postoperative complications. These preliminary observations suggest that dexamethasone irrigation during lumbar diskectomy is a safe and effective adjunct to surgical management. PMID- 2245549 TI - Chylothorax after posterior spinal instrumentation and fusion. AB - Chylothorax occurred in a 16-year-old girl after posterior spinal fusion and instrumentation for idiopathic scoliosis. Nonoperative management, including chest tube drainage for 26 days and total parenteral nutrition, successfully treated this unusual complication after a posterior spinal fusion. PMID- 2245550 TI - Newer concepts in antimicrobial therapy. AB - Advances in the treatment of infection have continued to increase both the length and quality of life. Unfortunately, many bacteria can readily adapt to their environment and develop a tolerance to the antimicrobial agents in widespread use. During the recent past, the consumption of cephalosporins has increased so dramatically as to parallel the initial acceptance of penicillin. Organisms that are resistant to the cephalosporins will no doubt continue to thrive, especially within the susceptible host. It is essential for the clinician to become familiar with the newest antimicrobial agents to more effectively treat modern infections. PMID- 2245551 TI - Peroneal nerve palsy after total knee arthroplasty. AB - The prognosis for peroneal palsy after total knee arthroplasty (TKA) is poorly defined. Twenty-six postoperative peroneal palsies occurred after 8998 TKAs performed between 1972 and 1985. Eighteen patients had complete and eight had incomplete peroneal palsies. Twenty-three had both motor and sensory deficits, and three had only motor deficits. At an average of 5.1 years (range, one to 11 years) after arthroplasty, recovery was complete for 13 palsies and partial for 12. Complete recovery was more likely in those palsies that were incomplete initially. Patients with palsies that were initially partial had significantly higher knee scores than those with complete palsies, and patients whose eventual recovery was complete had significantly higher knee scores than those with incomplete recovery. This new prognostic information should be useful for surgeons who encounter this unfortunate yet persistent complication of TKA. PMID- 2245552 TI - Knee function after complex femoral fractures treated with interlocking nails. AB - Twenty-three complex femoral fractures were treated with interlocking nails. After fracture healing, knee function was analyzed, including alignment, quadriceps and hamstring strength, thigh atrophy, and range of motion (ROM). Similar to previous studies in the preinterlocking nail era, knee function was impaired in comparison with the contralateral limb. Seventy-three percent of patients had decreased quadriceps strength, and 60% had decreased hamstring strength. Sixty-five percent had thigh atrophy. The ROM and alignment were satisfactory. Despite the advantages of early ROM with femoral fractures treated with interlocking nails, knee function is often unsatisfactory once fracture union has occurred. Therefore, a formal knee rehabilitation program is recommended to achieve an optimal result. PMID- 2245553 TI - Risk factors for the development of osteoarthrosis of the knee. AB - The roles of physical activity (both work and leisure time), obesity, and history of significant knee injury on the development of severe osteoarthrosis (OA) of the knee were evaluated. A case-control design compared 46 cases with a history of severe OA of the knee with 46 community controls matched for age and gender. Data were gathered with a self-administered questionnaire. The OA cases were 3.5 times more likely than controls to have been obese at 20 years of age, two to three times more likely than controls to have performed heavy work, and almost five times more likely than controls to have had a significant knee injury. In contrast, leisure-time physical activity was not significantly different in cases compared with controls. Obesity, significant knee injury, and long-term heavy physical activity are important risk factors for the development of OA of the knee. PMID- 2245554 TI - Echinococcus infestation of the biceps brachii. A case report. AB - Echinococcus is a genus of tapeworm endemic in certain parts of the world but found only rarely in the United States. An extremely unusual case of an intramuscular infestation involving an extremity occurred in a 41-year-old man. Since the infestation closely resembled a soft-tissue tumor on clinical and roentgenographic examination, the patient was treated with an incisional biopsy of the mass, which consisted of a cystic cavity filled with clear fluid. The diagnosis of an Echinococcus cyst was made only after permanent section analysis revealed numerous scoleces within the cyst lining. The patient was asymptomatic six months after cyst excision but still remains at risk for recurrence of the infestation. The present report serves to alert the reader to this rare but potentially fatal condition. Preoperative diagnosis is imperative to avoid inadvertant rupture of a hydatid cyst, which releases viable scoleces into the systemic circulation and may precipitate an anaphylactic reaction. PMID- 2245555 TI - Simplified two-stage below-knee amputation for unsalvageable diabetic foot infections. AB - A simplified two-stage below-knee amputation for unsalvageable diabetic foot infections was done on 19 limbs with 84% good results for healing. The first stage was the standard below-knee amputation with a long posterior flap in which the fascia and skin were closed in the central portion with the medial and lateral portions of the wound left open for drainage. The second stage was delayed until closure of the open wounds three to seven days after the first stage. Wagner's classification of diabetic foot lesions was used to stratify these cases. Grades 3 and 4 foot infections had a uniformly good prognosis for healing with this surgical technique. Grade 5 foot infections had a poor prognosis for healing, especially if associated with renal failure and dialysis, even with an initial guillotine amputation. PMID- 2245556 TI - Cartilage begets bone versus endochondral myelopoiesis. AB - Observations on the cellular events involved in embryonic long-bone formation, ectopic osteogenesis, fracture repair, and the analysis of mesenchymal stem-cell potential provide evidence of the intimate and direct relationship of osteogenesis to angiogenesis and vasculature. The sequence of cellular events is that cartilage is not replaced by bone but, rather, is a target for vascularization and myelopoiesis. With this in mind, it may be necessary to replace the term "endochondral bone formation" with "endochondral myelopoiesis." PMID- 2245557 TI - Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis. AB - Bone fragility during fluoride therapy for osteoporosis was observed in 24 (37.5%) of 64 patients treated with sodium fluoride, calcium, and vitamin D for 2.5 years who developed episodes of lower-limb pain during treatment. Eighteen (28%) of these patients had clinical and roentgenographic features of 41 stress fractures and 12 new spinal fractures. There were 26 periarticular, six femoral neck, three pubic rami, three tibia and fibula, one greater trochanter, and two subtrochanteric fractures. Vertebral fractures appeared first, then periarticular, then femoral neck, and lastly long-bone shaft fractures. All fractures were spontaneous in onset. The peripheral fracture rate during treatment was three times that in untreated osteoporosis. Roentgenograms must be repeated at intervals of three to four weeks before the pathognomonic callus becomes visible, and the diagnosis can be made. Trabecular stress fractures tend to occur in the first 18 months of treatment, and cortical stress fractures occur after 30 months of therapy. PMID- 2245558 TI - The various stress patterns of press-fit, ingrown, and cemented femoral stems. AB - Finite-element analysis was used to study the general differences in load transfer mechanisms and stress patterns of cemented, fully ingrown, proximally ingrown, and smooth press-fitted femoral stems in total hip arthroplasty (THA). Identical stems were used for the noncemented configurations and a similar stem shape for the cemented configurations. In each model, bone properties and loading characteristics were equal. Stem elastic moduli were varied so that the effects of cobalt-chromium-molybdenum (CoCrMo) and titanium as different stem materials could be assessed. The load-transfer mechanism is similar for all bonded configurations but differs dramatically for unbonded stems, e.g., press-fit designs. In the bonded configurations, interface stress concentrations occur on the proximal and distal sides. Stress value depends on stem rigidity, with higher proximal stress occurring in cemented stems and higher distal stress in noncemented stems. In the press-fit stem, the interface stresses are affected more by stem shape as a geometric entity and less by stem rigidity. Considering possible postoperative failure mechanisms, such as interface loosening and cortical bone loss, titanium is expected to produce better results in noncemented stems and CoCrMo in cemented stems. Cortical stress shielding as a qualitative phenomenon is caused by all stems, particularly in the calcar region. Quantitatively, stress-shielding effects differ with each type of fixation used. Stress-shielding effects are severe in fully ingrown stems and milder in cemented stems because of the differences in stem rigidity. The proximally ingrown stem falls between the fully ingrown and cemented stems in regard to stress shielding because stress transfer is more evenly distributed along the stem and concentrated at the lower coated edge. The press-fit stem provokes calcar stress shielding only. In the midstem region the stresses in the cortex are even greater than in the natural case. PMID- 2245560 TI - Histopathologic interpretations. PMID- 2245559 TI - The fat embolism syndrome. A review. AB - While fat embolism occurs in most (more than 90%) patients with traumatic injury, the fat embolism syndrome (FES) occurs in only 3%-4% of patients with long-bone fractures. FES involves multiple organ systems and can cause a devastating clinical deterioration within hours. The major clinical features of FES include hypoxia, pulmonary edema, central nervous system depression, and axillary or subconjunctive petechiae. Improvements have been made in supporting the respiratory compromise and adult respiratory distress syndrome that these patients develop. Aggressive measures to improve the pulmonary function, i.e., positive pressure ventilation and effective fluid management, are important and expedite fixation of bone fractures. PMID- 2245561 TI - Osteo-arthritis of the hip joint. 1939. PMID- 2245562 TI - Hydroxyapatite-coated total hip prostheses. Two-year clinical and roentgenographic results of 100 cases. AB - Studies of implant fixation have shown that hydroxyapatite (HA) coatings provide early and strong fixation to bone. This is a report of 100 consecutive cases of total hip arthroplasties, using HA coating, which were mainly for osteoarthrosis, avascular necrosis, or revision for failed implants. The average prospective follow-up period was two years. Titanium femoral components had a proximal HA coating, usually with an HA-coated screw cup. For both HA-coated components, the average Harris hip score was 96 points after one year and 98 after two years. Analysis of data shows that the incidence of pain was low immediately after surgery and at 4% one year postoperatively. There was no difference between the results of primary cases and revisions after the one-year interval. On roentgenographic examination, there was a rapid bony integration of implants with bone apposition on the coating within six months, accompanied by specific patterns of remodeling. No radiolucent line formation was detected around HA coated implant parts. There were no revisions for loose implants. After two years, 97% of the patients had positive roentgenographic evidence of femoral ingrowth compared to 55% for HA-coated acetabular cups, with a statistical significance between bone ingrowth and clinical results. Implant fixation using HA coatings is a reliable procedure for good bony fixation and clinical results. PMID- 2245563 TI - Bipolar versus total hip arthroplasty for avascular necrosis of the femoral head. A comparison. AB - In a relatively small series of cases the results of bipolar prostheses in avascular necrosis were inferior to those of total hip arthroplasty (THA). Femoral loosening rates were not reduced by using bipolar prostheses. THA produced more inferior results in avascular necrosis than in degenerative joint disease. Early results of noncemented THA for avascular necrosis were good but also must withstand the test of time. A fixed noncemented acetabular component was preferable over a bipolar prosthesis for avascular necrosis of the femoral head. PMID- 2245564 TI - The case for porous-coated hip implants. The femoral side. AB - A series of 1163 total hip arthroplasties (THAs) using porous-coated femoral components were roentgenographically assessed for implant fixation. For 959 primary THAs followed from two to 12 years, the femoral revision rate was 1% and the ten-year survivorship rate was 96.4%; 150 young patients had a fixation failure incidence of only 1.3% at a mean follow-up period of 6.4 years; in 204 revision THAs, the femoral re-revision rate was 4% at a mean follow-up period of 53.4 months. Failures were largely related to inadequate femoral canal filling. Because of refinements in implant design and surgical techniques, a press fit of the implant is currently achieved in 94% of cases compared to 36% during the first five years. Porous-coated femoral components have yielded results equivalent to those with cement in primary THAs. Excellent results were observed in relatively young patients and patients with revisions. PMID- 2245565 TI - Magnetic resonance imaging evaluation of congenital dislocation of the hips. AB - Magnetic resonance (MR) images were obtained preoperatively and postoperatively for 12 pediatric patients with congenital dislocation of the hip (CDH). The images were compared with arthrograms and computed tomography scans. The MR images were more accurate in defining soft-tissue anatomy, hip position, and obstructive factors to relocation. MR imaging is an efficient diagnostic tool in CDH. PMID- 2245566 TI - The George Simon lecture: magnetic resonance studies of the heart. PMID- 2245567 TI - The impact of the M1 air crash on the radiological services at the Queen's Medical Centre, Nottingham. AB - Following the M1 air crash on 8 January 1989, 39 casualties were taken to the Queen's Medical Centre, Nottingham. A team of 31 radiographers and four radiologists used all five X-ray rooms adjacent to the Accident and Emergency Department. Patients with head and spinal injuries were further assessed in the CT suite by four radiographers and a neuroradiologist. The volume of work in the first few hours and in the subsequent days is described. All radiological examinations have been reviewed and the injuries, including those missed at initial assessment, are discussed. The role of the radiologists was to issue immediate reports, manage examinations so as to minimize any delay and assess the need for further specialized investigation. Important problems were identified, specifically: the call-out system; patient deterioration and lack of resuscitation equipment; patient flow; documentation; radiology equipment; and missed injuries. These problems are discussed and recommendations are made for X ray Departments in dealing with disasters. PMID- 2245568 TI - CT evidence of intracranial contusion and haematoma in relation to the presence, site and type of skull fracture. AB - The skull films and CT scans of 1383 patients with acute head injury transferred to a regional neurosurgical unit were reviewed. Of the 850 patients with a skull fracture, contusion and/or haematoma was found in 71%, compared with 46% of the 533 patients with no fracture. Thirty-nine per cent of patients had neither contusion nor haematoma, and 21% had neither skull fracture nor contusion/haematoma. Haematomas occurred more frequently in association with lateral and occipital fracture than with frontal fracture, but the incidence of contusion was similar for all fracture sites. Linear fractures were more often associated with extra- and subdural haematomas than were depressed fractures. Intracranial damage associated with depressed fractures was localized more frequently than with linear fractures. Frontal fractures were rarely associated with posterior damage alone, but with occipital fractures anterior contusion was more frequent than posterior. Damage associated with lateral fracture was solely contralateral in 26%. Skull fracture was present in 77% of patients with contusion, 87% of those with an extradural, 72% with a subdural, and 66% with an intracerebral haematoma (70% of all those with an intracranial haematoma). PMID- 2245569 TI - The effect of radiology guidelines for general practitioners in Plymouth. AB - The impact of introducing guidelines to General Practitioners using the radiodiagnostic services in the Plymouth Health District has been analysed. The guidelines were advisory and issued to all General Practitioners in the area served by the Plymouth group of hospitals. There was no vetting of requests from Practitioners following their introduction. Three 6 month periods were considered; two before the guidelines were introduced and one after. An overall reduction of 23% in referrals was achieved. An analysis by examination showed that only those examinations specifically targeted in the guidelines showed a significant reduction. In the case of targeted examinations, a reduction of 28% (P less than 0.001) was demonstrated. PMID- 2245570 TI - Duplex ultrasound of the abdominal aorta--a neglected tool in aortic dissection. AB - The use of duplex ultrasound for the diagnosis and assessment of abdominal aortic dissection and visceral arterial involvement is discussed. Ultrasound is simple and non-invasive and may be superior to aortography in diagnosis; it should be performed after ultrasound assessment of the aortic root. It also provides an effective means of follow-up evaluation if conservative treatment is employed. Three cases are discussed in whom there was no operative intervention. In one case, aortography failed to make a positive diagnosis of aortic dissection. The diagnosis was made by ultrasound in all three cases, one of whom was found subsequently to have Marfan's syndrome. PMID- 2245571 TI - The accuracy of computed tomography of the liver in colo-rectal carcinoma. AB - A prospective study in 71 patients with colo-rectal carcinoma was undertaken to evaluate the accuracy of computed tomography (CT) of the liver and arterially enhanced liver CT (CTA). The results were initially based on the findings at surgery. The accuracy of CT was 82% and CTA 84%. Since the evaluation of the liver at surgery is not always correct, a clinical follow-up and repeat CT in the same group of patients was performed. The intention was to search for occult metastatic disease of the liver and thus more accurately evaluate the results of CT, CTA and the surgical evaluation at laparotomy. Both the presence or absence of tumour, as well as the distribution of tumour growth in the liver were considered. In comparison with the results of the follow-up, CT detected the presence and correctly described the tumour distribution in 86%, CTA in 87%, and the surgeon in 88% of the cases, respectively. CTA is recommended if the CT scan is negative or if a more detailed evaluation is required prior to liver resection. PMID- 2245572 TI - Echo enhancement behind solid intra-hepatic metastases: a potential pitfall in diagnosis. AB - Posterior echo enhancement is rightly considered a reliable sign of a cystic lesion. Three examples are given of solid metastatic deposits present within fatty livers which showed posterior echo enhancement. The reason for this finding is discussed and the importance of distinguishing such lesions from abscesses is emphasized. PMID- 2245573 TI - Heel pad thickness is an insensitive index of biochemical remission in acromegaly. AB - The value of serial measurements of heel pad thickness as a clinical predictor of biochemical remission in acromegaly was assessed in 25 patients followed for up to 20 years after treatment by interstitial irradiation using yttrium-90 implantation. Growth hormone (GH) levels fell to 50% of baseline values within 12 months of therapy (P less than 0.001) and to 21% at 5 years, reaching normal levels after 10 years, constituting a biochemical cure maintained to the end of the study period. By contrast, heel pad thickness remained relatively stable, falling to 95% of baseline after 5 years (P less than 0.05) and to 87% after 20 years. There was no overall correlation between the measured parameters (r = 0.033, P greater than 0.05) suggesting that heel pad thickness is a poor predictor of biochemical remission in acromegaly. PMID- 2245574 TI - Technical report: digital subtraction dacryocystography. AB - Twenty-one patients presenting clinically with obstructive epiphora were investigated by digital subtraction dacryocystography (DSDCG). This technique is quick and simple to perform, with good patient acceptance. It produces diagnostic images on a single radiographic projection. The proximal lacrimal apparatus is well demonstrated. Patient radiation dose to the orbit is apparently reduced in DSDCG without the use of lead eye shields. The technique of DSDCG was readily acquired by junior radiologists. Reliable and accurate demonstrations of lacrimal duct obstructions were produced in a general radiological department where dacryocystography is an occasional examination. We advocate the use of digital techniques in dacryocystography when the equipment is available. PMID- 2245575 TI - Case report: MRI diagnosis of congenital absence of the internal carotid artery. AB - Congenital absence of the internal carotid artery is a rare anomaly that has previously required angiography for diagnosis. Magnetic resonance imaging (MRI) provides good visualization of major arterial structures, and in this case documented the absence of the left internal carotid artery. PMID- 2245576 TI - Case report: recurrent liposarcoma of the oesophagus. AB - A case of recurrent liposarcoma of the oesophagus is presented. The clinical and radiological findings are discussed. Our case displays the characteristic features and behaviour of a common sarcoma arising in a rare site. PMID- 2245577 TI - Case report: mesenchymal chondrosarcoma occurring in the parapharyngeal space. AB - Mesenchymal chondrosarcomas are rare tumours, the minority arising in an extraskeletal site. We describe a case of extraskeletal mesenchymal chondrosarcoma occurring in the parapharyngeal space. This was demonstrated by computed tomography (CT), magnetic resonance imaging (MRI) and angiography. PMID- 2245578 TI - The Royal College of Radiologists Annual Scientific Meeting. 18-21 September 1990, Edinburgh.Abstracts. PMID- 2245579 TI - Renal excretion of enteral gastrografin. PMID- 2245580 TI - A hypoechoic area within the head of the pancreas. PMID- 2245581 TI - Incidence and sites of medial thigh communicating veins. PMID- 2245582 TI - Preoperative localization for primary hyperparathyroidism. PMID- 2245583 TI - Monitoring of recovery following exercise in the Doppler ultrasound evaluation of lower limb arterial disease. AB - Measurement of the ratio of ankle to brachial systolic blood pressure (pressure index) is an integral part of the Doppler ultrasound investigation of lower limb arterial disease. The recovery of this index following exercise gives further information regarding the clinical significance of the disease. However, serial sphygmomanometry may prolong recovery time by intermittent reduction of blood flow and for certain categories of patients the technique may prove impossible or will lead to unreliable results. The aim of this study was to investigate the use of Pourcelot's Resistance Index, measured from the Doppler blood velocity spectrum, as an alternative means of monitoring recovery. The results show that peripheral resistance is likely to fall following pressure measurement, indicating a potential effect on recovery time. There is reasonable correlation between post-exercise pressure and resistance indices (r = 0.69, P less than 0.001), and good correlation between their recovery times (r = 0.84, P less than 0.001) with no systematic deviation. Resistance index is therefore a viable alternative to pressure index for the monitoring of post-exercise recovery, and overcomes the problems associated with sphygmomanometry. PMID- 2245584 TI - Measurement of stiffness during simulated spinal physiotherapy. AB - A new device was designed to simulate a physiotherapist's assessment of spinal stiffness. The device applies an oscillating postero-anterior force over a spinous process and the force-displacement relation is measured. From these data the stiffness of the movement can be computed. The accuracy and repeatability of stiffness values were found to be high when an elastic beam was tested. Test retest reliability in 11 human subjects was investigated and found to be good. PMID- 2245585 TI - Evaluation of bioelectrical impedance analysis for body composition measurements in anorexia nervosa. AB - Many established methods of measuring body composition are time consuming and require complex equipment which is not generally available. Bioelectrical impedance analysis is a technique which utilises the difference in conductivity between fat and lean tissues at radiofrequencies. It uses inexpensive equipment which is simple to use and does not involve the use of ionising radiation. We have evaluated this technique in 44 studies on 38 anorexic females with a wide range of body mass index. Fat free mass was obtained from the mean of three established methods. The initial calibration was derived from 21 studies on 19 anorexics. Fat free mass was regressed against impedance and body habitus parameters to establish the prediction equation with the smallest standard error (1.12 kg). Values of fat free mass derived using this prediction equation were then compared with the other methods in a prospective study. The error of the bioelectrical impedance technique compares favourably with the established methods, even in anorexic patients with very low body mass index. PMID- 2245586 TI - Hand-held compared with isokinetic dynamometry for measurement of static knee extension torque (parallel reliability of dynamometers). AB - The purpose of this study was to compare measurements of static knee extension torque obtained using a hand-held dynamometer (HHD) and an isokinetic dynamometer (IKD). Twenty young healthy women performed two maximum knee extension efforts against each device. The two HHD measurements did not differ significantly and were highly reliable (intraclass correlation coefficient (ICC) = 0.945). The two IKD measurements did not differ significantly and were highly reliable (ICC = 0.932). The mean of the two HHD and two IKD measurements did not differ significantly. The inter-instrument reliability was fair (ICC = 0.797). Thus, under limited circumstances the instruments may be interchangeable. The less expensive and more portable HHD may be a practical alternative for the clinical measurement of muscle strength. PMID- 2245587 TI - A transputer implemented algorithm for electrical impedance tomography. AB - Electrical impedance tomography (EIT) offers a non-invasive technique of great scope for producing clinically important information in a number of medical applications. Initial work by Brown used an isopotential approach to solving the complex backprojection problem. In this study a less restrictive algorithm for EIT has been developed based on the work of Yorkey and of Kaczmarz. Since considerably more processing is required this has been implemented on a transputer in Occam 2 with the aim of achieving real-time imaging. Data were collected, using a Sheffield prototype EIT system, from a test object and a human thorax. Image processing used both the 'Sheffield' and the Yorkey/Kaczmarz algorithms. Our initial results indicate that the images generated using the latter approach were more representative of the source impedance distributions. PMID- 2245588 TI - Practical experience in electromagnetic hyperthermia quality control procedures within the context of international guidelines. AB - Recent international guidelines on hyperthermia (HT) quality assurance have pointed out the necessity of defining standard operative procedures and technical checks to guarantee an accurate performance of HT treatments. In the present paper, experience is described of quality control procedures that are performed in agreement with the more general guidelines concerning thermometry, sensor positioning, phantoms, applicator characterisation, and electromagnetic (EM) radiation leakage. This practical experience comes from the use of equipment for superficial and loco-regional HT working in the range 13.56-915 MHz. PMID- 2245589 TI - A contact method for the assessment of ultrasonic velocity and broadband attenuation in cortical and cancellous bone. AB - A portable system using a direct contact for the measurement of ultrasonic velocity and broadband attenuation in bone is described (contact ultrasonic bone analyser, CUBA). Soft-tissue compensation is performed using an ultrasonic pulse echo technique. CUBA has been successfully validated using reference materials, the precision of velocity and broadband attenuation measurements being typically 0.2% and 0.5% respectively. The clinical reproducibility has been assessed on the equine third metacarpal bone. The reproducibility of velocity measurement is typically 0.5% for cortical bone and 1% for cancellous bone. For broadband attenuation the reproducibility is typically 7% for cortical bone and 6% for cancellous bone. The lower reproducibility of the attenuation data is attributed to the high sensitivity to variations in the material properties of bone with small changes in transducer positioning. Coupling difficulties through an intact equine coat have been overcome and the system may now be assessed in the clinical environment, in both human and animal populations. PMID- 2245590 TI - Appropriate diagnostic technology. PMID- 2245591 TI - Spine densitometry--further comments on errors. PMID- 2245592 TI - Endothelium-derived relaxing factor (EDRF) and nitric oxide (NO). I. Physiology, pharmacology and pathophysiological implications. PMID- 2245593 TI - Diminished meal-induced thermogenesis in elderly man. AB - The purpose of this study was to examine the possible influence of age on thermogenic response to a mixed meal in healthy subjects. Twenty-five healthy male subjects participated in the study and they were divided into three groups, comprising 10 young subjects with an average age of 27 years (22-35 years), seven middle-aged individuals (51 years, 42-60 years) and eight elderly men (70 years, 67-74 years). They were all studied with continuous indirect calorimetry in the basal state and for 3 h after the ingestion of a mixed meal in liquid form. The size of the meal corresponded to 60% of the individually computed 24-h basal energy expenditure. Resting energy expenditure was lower in the elderly men than in the young ones when expressed in absolute values (P less than 0.001) as well as in relation to body weight (P less than 0.01) and body surface area (P less than 0.01). After the meal energy expenditure increased rapidly and reached a relatively constant level after 60 min in all groups; the average increase above the basal level during the whole postprandial period was less in the elderly (21.1 +/- 2.5%, P less than 0.01) and the middle-aged (24.2 +/- 1.7%, P less than 0.05) than in the young (28.6 +/- 1.6%) men. It is concluded that the thermogenic response during the first 3 h following a mixed meal decreases with age and that this diminished meal-induced thermogenesis may contribute to lower nutrient requirements in old age. PMID- 2245594 TI - Effect of acquisition and analysis routines on gated blood pool measurements. AB - Results obtained from gated equilibrium blood pool (GBP) studies are not only dependent on intrinsic variations, but also on the way in which images are acquired and analysed. The aim of this study was to investigate factors which could affect left ventricular time-activity curves. Temporal resolution was studied by comparing studies of 20 and 40 frames beat-1. Forty frames per beat resulted in a mean left ventricular ejection fraction of 0.48 compared to 0.46 for 20 frames beat-1. The mean difference of 0.02 was significant (P less than 0.01) as was the mean difference in maximum emptying rate (MER = 0.28, P less than 0.01) and in maximum filling rate (MFR = 0.38, P less than 0.01). No significant differences in ejection fraction (EF) values were found between acquisitions made in list and frame mode, but the mean differences for MER = 0.03 (P less than 0.05) and MFR = 0.01 (P less than 0.02) were significant. For patient repositioning and intra-observer variations no significant differences were found. In patients with normal EF values (greater than 0.5) no significant differences were found in the inter-observer study. In patients with anterior myocardial infarction (AMI), significant differences were found in EF, MER and MFR (EF = 0.02, P less than 0.001; MER = 0.2, P less than 0.01; MFR = 0.24, P less than 0.01). Significant differences were found in all values when comparing a semi-automatic method of evaluation with two automatic methods. In conclusion the results from this study suggest that acceptable reproducibility can be achieved in GBP studies, provided the method of analysis is not changed between studies. PMID- 2245595 TI - Nailfold capillaroscopy in non-insulin dependent diabetes mellitus: blood flow velocity during rest and post-occlusive reactive hyperaemia. AB - Direct intravital microscopic examinations of nailfold capillaries were made in two groups of subjects: 15 healthy volunteers (C) and 16 non-insulin dependent (D II) diabetic patients. In the diabetic group, the disease duration was less than 1 year (n = 4), between 1 and 10 years (n = 8) and between 10 and 18 years (n = 4). Capillary morphology was evaluated and the distribution of morphological patterns was significantly different between the two groups (P less than 0.001). The number of enlarged capillaries was increased in the D II group compared to the C group and capillaries with nodular apical elongations were only found in diabetics. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60 s arterial occlusion. To assess autoregulatory capacity we determined peak CBFV post occlusion and time to reach it in single capillaries. Mean resting CBFV was not statistically different in the two groups but mean peak CBFV post occlusion was significantly lower (C: 1.49 +/- 0.14 mm s-1; mean +/- SE; D II: 0.93 +/- 0.13 mm s-1, P less than 0.05) and mean time to reach it significantly prolonged (C: 8.9 +/- 0.6 s; D II: 18.0 +/- 1.9 s; P less than 0.05) in diabetics compared to controls. Thus skin microvascular autoregulatory responses are disturbed in these patients. The impairments of the reactive hyperaemia response could not be correlated to either metabolic control or duration of the disease. PMID- 2245596 TI - Cardiac output determined by ultrasound-Doppler: clinical applications. AB - A non-invasive method for cardiac output determination (COD) based on ultrasound Doppler technique was evaluated in patients with cardiac disease at rest and during exercise, including patients with heart transplants. The aortic blood flow velocity was measured with pulsed Doppler technique from the jugulum, placing the sample volume just above the aortic valve, and the area from a parasternal 2-D echocardiographic measurement of the aortic annulus diameter assuming a circular area. Cardiac output was calculated as the product of the systolic velocity integral, the aortic annulus area and the heart rate. A high correlation was found between this method and a simultaneously performed invasive cardiac output (COF) and stroke volume (SVF) determination by the direct Fick method (COD = 0.3 + 0.9 x COF, r = 0.96, SDres = 0.5 l min-1 and SVD = 3.9 + 0.92 x SVF, r = 0.94, SDres = 6.9 ml). However, looking just at the systolic velocity integral compared to stroke index determined with the Fick method we found a low correlation, especially in patients with heart transplants. We conclude that cardiac output can reliably be measured non-invasively with this method--also in patients with heart transplants. The systolic velocity integral alone can be used for assessing changes in stroke volume but for absolute values of stroke volume and stroke index flow area should also be determined. PMID- 2245597 TI - Combined left and right ventricular volume determination by radionuclide angiocardiography using double bolus and equilibrium technique. AB - Eighteen patients with ischaemic heart disease were studied. Left and right ventricular volumes including cardiac output (forward flow) were determined by radionuclide angiocardiography using a double bolus and equilibrium technique. As reference, cardiac output was simultaneously measured by indicator dilution. The radionuclide technique comprised four steps: (1) a first-pass study of right ventricle; (2) a bolus study of left ventricle; (3) an equilibrium study of left ventricle; (4) determination of the distribution volume of red blood cells. Absolute volumes of left ventricle were determined from steps 2 + 3 + 4. Absolute volumes of right ventricle were calculated from stroke volume and right ventricular ejection fraction (EF) which in turn was determined from step 1 by creating composite systolic and composite diastolic images. There was an acceptable agreement between stroke volume determinations by radionuclide angiocardiography and indicator dilution (r = 0.74; P less than 0.001). Stroke volume determination by radionuclide was 83 +/- 20 ml (mean +/- SD) and by indicator dilution 84 +/- 20 ml with a difference of -1 +/- 15 ml (NS). Cardiac output determination by radionuclide was 5.24 +/- 1.37 l min-1 and by indicator dilution 5.28 +/- 1.23 l min-1 with a difference of -0.04 +/- 0.95 l min-1 (NS). Left ventricular EF was 0.44 +/- 0.14 and right ventricular EF 0.57 +/- 0.10. The intra-observer coefficient of variation for duplicate calculations of the radionuclide determinations was 5.5% for stroke volume, 2.5% for left ventricular EF and 4.8% for right ventricular EF. PMID- 2245598 TI - Reflex actions of knee joint afferents during contraction of the human quadriceps. AB - (1) The spinal reflex actions of afferents stimulated by knee joint distension have been investigated in man. (2) Cannulation of the knee and infusion of saline raised intra-articular pressure, especially during quadriceps contraction. High pressures did not induce any sensation of pain. Pressure was taken as an index of joint proprioceptor activation. (3) Increased pressure progressively depressed the quadriceps H-reflex, both at rest and during quadriceps contraction. There was no indication of a threshold pressure for this inhibitory action. (4) It is concluded that joint distension inhibits quadriceps motoneurons through spinal pathways that still operate during voluntary contraction. These pathways could thus contribute to pathological weakness after joint injury. (5) Joint distension produced spatial facilitation of non-reciprocal inhibition of quadriceps H reflexes from afferents in the tibial nerve. PMID- 2245599 TI - Effects of surgical treatment and immobilization on the healing of the medial collateral ligament: a long-term multidisciplinary study. AB - The long-term effects of surgical repair and immobilization on the healing of the transected medial collateral ligament (MCL) were studied biomechanically, biochemically and histologically in a canine model. Twelve adult canines were divided into two experimental groups and studied at 48 weeks postoperatively. For Group I, the transected MCL of the left knee was not repaired, and the joint was not immobilized. For Group II, the MCL was repaired and the joint was immobilized for six weeks. The right knee of each canine was sham-operated and served as the control. Histologically, the collagen fibers were less aligned in both of the experimental groups than in the controls. Furthermore, there were minimal differences in collagen and fibroblast alignment between the groups, although poorer alignment was observed for Group I at 12 weeks. Biochemically, the levels of types I and III collagen, reducible collagen cross-links and total collagen concentration for both groups returned to normal levels. Biomechanically, Group I achieved better results than Group II in terms of varus-valgus (V-V) knee rotation and ultimate load of the femur-MCL-tibia complex (FMTC), as these values returned to the level of controls. However, the mechanical properties of the healing MCLs did not compare well with the controls; the tensile strength was only 62% and 45% of controls for Groups I and II, respectively, at 48 weeks. These results suggest that conservative treatment (i.e., no surgical intervention) with early mobilization is better than surgical treatment with immobilization for an isolated Grade III MCL injury. PMID- 2245600 TI - Changes in vascular extracellular matrix accumulation reflect phenotypic differences between the arterial wall of pigeons resistant and susceptible to the development of spontaneous atherosclerosis. AB - White Carneau pigeons have previously been shown to be genetically susceptible to the development of spontaneous atherogenesis. The severity of development of atheromatous lesions is considerably greater than a more resistant breed of Show Racer pigeons. Analysis of levels of total hydroxyproline and isodesmosine in the thoracic aorta and celiac bifurcation of prelesion, six-week-old White Carneau and Show Racer pigeons, revealed an increased accumulation of total collagen and cross-linked elastin in the White Carneau arterial tissue. Using dot blot hybridization, measurements of steady state levels of several mRNAs in total RNA extracted from pigeon aortic tissue were also determined. While the increased deposition of extracellular matrix proteins was paralleled by a significantly greater recovery of mRNAs coding for pro alpha 1(1) collagen and elastin, in RNA extracted from White Carneau aortal tissue, increased recovery of mRNAs coding for an intracellular protein, gamma-actin were also observed in White Carneau aortal tissue. No differences in steady state levels of mRNAs coding for pro alpha 1(1) collagen and elastin were observed in RNA extracted from pigeon liver, suggesting a tissue specific increase in the mRNAs coding for these connective tissue proteins in aorta. A markedly reduced cell population however, was responsible for this overall increase in biosynthetic activity in White Carneau pigeon aortic tissue. This was demonstrated by a reduced cell count and by the recovery of reduced levels of total DNA in the thoracic aorta and celiac bifurcation of the White Carneau pigeon. The cell population in White Carneau aortic tissue exhibits therefore a markedly different phenotype with respect to a capacity for the biosynthesis of extracellular and intracellular proteins. PMID- 2245601 TI - Changes in steady-state levels of mRNAs coding for type IV collagen, laminin and fibronectin following capillary basement membrane thickening in human adult onset diabetes. AB - The development of capillary basement membrane thickening has been linked to microvascular changes known to occur in tissues of patients with type II diabetes. Previous evidence has suggested that capillary basement membrane thickening is due to increased basement membrane synthesis. In this study, skin samples from 8 diabetic patients with confirmed capillary basement membrane thickening and 7 non-diabetic controls were used to assess steady state levels of mRNAs coding for several basement components including pro alpha 1(IV) collagen, laminin and fibronectin. Total RNA was extracted from abdominal skin samples and levels of mRNAs coding for the basement membrane components laminin, fibronectin and pro alpha 1(IV) collagen, a fibrillar collagenous protein, pro alpha 1(I) collagen and an intracellular polypeptide, gamma-actin, were determined by dot blot hybridization analysis. While there were no changes of steady state levels of pro alpha 1(I) collagen mRNA and laminin mRNA, a significant reduction was noted in the quantitative recovery of mRNA levels for pro alpha 1(IV) collagen, gamma-actin and fibronectin in total RNA isolated from the skin of diabetic patients. This reduction in levels of mRNAs coding for basement membrane components contrasts with pathological confirmation of an accumulation of endothelial capillary basement membrane in skin from diabetic patients and suggests that basement membrane thickening arises more as a consequence of reduced basement membrane degradation than elevated synthesis of basement membrane components. PMID- 2245602 TI - Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome. AB - HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain of endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody. Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment. HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay. A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99). The mean +/- SEM apparent volume of distribution of HA-1A was 48.5 +/- 4.5 ml/kg, and the mean serum clearance was 2.8 +/- 0.4 ml/kg.h. The mean serum half-life of HA-1A was 15.9 +/- 1.5 h. The mean serum level one hour after a 100 mg dose was 33.2 +/- 2.4 micrograms/ml, and the mean concentration 24 h later was 9.1 +/- 1.6 micrograms/ml. The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance. No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient. These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis. PMID- 2245603 TI - Dependence of oxygen consumption on oxygen delivery in children with hyperdynamic septic shock and low oxygen extraction. AB - We studied the effect of increasing systemic oxygen delivery (DO2) by packed RBC (PRBC) transfusion on oxygen consumption (VO2) in children with hyperdynamic septic shock. After routine resuscitation with volume loading and pharmacologic support, patients were studied if they had significant derangements of oxygen transport variables defined as: baseline VO2 less than 180 ml/min.m2 and oxygen extraction (O2 extr) less than 24%. Eight studies were performed. PRBC transfusion increased DO2 from 636 +/- 167 to 828 +/- 266 ml/min.m2 (p less than .01) without increasing cardiac index (5.2 +/- 1.3 vs. 5.0 +/- 1.4 L/min.m2). VO2 increased from 112 +/- 36 to 157 +/- 60 ml/min.m2 (p less than .01) while O2 extr was unchanged (18 +/- 3% vs. 19 +/- 6%). Despite initial low O2 extr, VO2 can be increased in pediatric septic shock by a further increase in DO2. Since VO2 correlates with survival, one should consider enhancing DO2 further despite initial low O2 extr and high DO2. Effects on morbidity and mortality require further study. PMID- 2245604 TI - Swallowing disorders in patients with prolonged orotracheal intubation or tracheostomy tubes. AB - Eleven patients were tested for swallowing dysfunction after prolonged orotracheal intubation. Ten had a tracheostomy tube. Mean duration of orotracheal intubation was 19.9 days, mean age 65 yr, and no patient had a concomitant neurologic deficit. All patients had a modified barium swallow with videofluoroscopy. All patients had at least one defect of 11 defects characterized. There was a mean of six defects/patient. The most common defects were delayed triggering of the swallow response (present in all patients) and pharyngeal pooling of contrast material (n = 9). Follow-up videofluoroscopy was performed in five patients (all had improved) with mean defects decreasing from 6.1 to 2.8/patient. With one exception, no patient had any defect that was worse than mild in severity. We concluded that prolonged orotracheal intubation with or without tracheostomy may cause prolonged and severe swallowing dysfunction. The deficits improve with time. The presence of a gag reflex does not confer protection against aspiration of pharyngeal contrast. PMID- 2245605 TI - Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. AB - In patients with acute liver failure and hepatic coma, an increase in the abnormal "middle molecules" seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived greater than 3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant. PMID- 2245606 TI - Accuracy in early prediction of prognosis of patients with septic shock by analysis of simple indices: prospective study. AB - In 26 consecutive septic shock patients, we analyzed the clinical, hemodynamic, and metabolic data before and during volume infusion to test their circulatory reserve in response to fluid repletion. These patients were investigated to identify early variables that could predict outcome. There were 15 survivors (group A) and 11 nonsurvivors (group B). As a mean, group A patients were hemodynamically evaluated 2.3 h after onset of the sepsis syndrome, whereas group B patients underwent cardiac catheterization after a 12-h interval. At the initial evaluation, both groups demonstrated similarly decreased mean arterial pressure, mean heart rate, and mean cardiac filling pressure. Only group A patients evidenced elevated cardiac index (CI) (greater than 4 L/min.m2) associated with low systemic vascular resistance index (less than 7400 dyne.sec/cm5.m2), which is generally recognized as hyperdynamic cardiac state. However, none of the initial cardiovascular variables could serve as a predictor for survival. Fluid challenge increased left ventricular preload from 6 to 12.4 and from 7.8 to 12.7 mm Hg in group A and group B, respectively. The increases were associated with significant increases in CI from 4.4 to 6.9 and from 3 to 3.8 L/min.m2. However, at the end of fluid challenge, only group A patients exhibited normal cardiac response, as evidenced by the change in left ventricular stroke work index (LVSWI) for a given increase in the pulmonary capillary wedge pressure (WP) that was referred to as left cardiac preload.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245607 TI - Critical Care Scoring System--new concept based on hemodynamic data. AB - Based on the rationale that hemodynamic, oxygen transport, and perfusion derangements describe physiologically important abnormalities in critically ill patients, we devised a Critical Care Scoring System (CCSS). The database includes a retrospective analysis of 318 patients managed with pulmonary artery catheters during 1986 to 1988. For comparison, Acute Physiology and Chronic Health Evaluation (APACHE II) score was computed for these patients. CCSS includes a total of 17 variables with a weighted score of 71. The mortality rates for increases by 5 points were observed and were statistically significant (p less than .0001). The same was not true for APACHE II. Although neither of the scores could predict ICU days, both reflected the number of life-threatening complications. Serial CCSS that was computed at 24 +/- 4 h (CCSS-C) provided documentation for improvement in patient condition secondary to therapeutic interventions. Statistically improved mortality prediction was observed with CCSS C. Since 70 (45.7%) of 153 patients died with an APACHE II score less than 14, it appears that this score is deficient in a specific group of patients, i.e., those requiring invasive monitoring. For patients with circulatory or respiratory failure, CCSS may offer a better tool to predict mortality and evaluate therapy. PMID- 2245608 TI - Relationship between clinical evaluation of peripheral perfusion and global hemodynamics in adults after cardiac surgery. AB - The relationship between clinical indicators of peripheral perfusion and global hemodynamics after cardiac surgery was examined in 40 adults. We found no significant relationship between capillary refill, pedal pulses, or extremity (toe or finger) core temperature gradients and cardiac index (CI) or systemic vascular resistance index immediately after surgery on the day of operation. However, on the first postoperative day we did observe a crude (r = -.60) correlation between CI and toe-core temperature gradient. PMID- 2245609 TI - Does prematurity alter the course of respiratory syncytial virus infection? AB - We compared previously healthy prematurely born infants with full-term infants hospitalized with respiratory syncytial virus (RSV) infection to evaluate the role of prematurity on the clinical course of the illness. During a 5-yr period (1984 to 1989), 484 previously healthy patients were admitted to the hospital with RSV infection. No differences were found in the presenting symptoms of respiratory distress, cough, fever or shock, although the premature group was more likely to present with apnea (p less than .001). Chest roentgenograms revealed that premature infants had a higher incidence of atelectasis/infiltrate and hyperinflation (p less than .05). Premature infants had longer hospital stays as well as a higher Physiologic Stability Index and Therapeutic Intervention Score (p less than .001). They were also more likely to receive supplemental oxygen, ICU admission, mechanical ventilation, and nothing by mouth status (p less than .001). We conclude that premature birth increases the risk of more severe and prolonged RSV disease. PMID- 2245610 TI - Alterations in pulmonary mechanics after transfusion in anemic preterm infants. AB - Pulmonary mechanics were studied in ten anemic preterm infants using an esophageal balloon and mask, before and after transfusion with 10 ml/kg of packed RBC. Their mean birth weight was 1212 +/- 323 g and gestational age was 29.27 +/- 2.4 wk. Transfusions were carried out at a mean postnatal age of 41.9 +/- 21.8 days. The mean Hct increased from 28 +/- 3.1 to 38.3 +/- 3.3%. Dynamic lung compliance decreased in all infants after transfusion. There was a 33.8% increase in resistance; the work of breathing increased after transfusion. These changes might be due to volume overload or increased lung water content. PMID- 2245611 TI - Femoral artery cannulation for monitoring in critically ill children: prospective study. AB - Seventy-seven attempted percutaneous femoral artery cannulations were prospectively evaluated in 74 children. Artery cannulation was successfully accomplished in 73 (95%) cases and lasted for a mean of 6 days. Sixty percent of the catheters were inserted on the first attempt. Fifty-two (71%) patients weighed less than 10 kg and 55 (75%) patients were less than 12 months old. Fifty one (70%) patients received inotropic support at the time of cannulation, and 27 (37%) eventually died from causes unrelated to catheter insertion. There was one episode each of line-associated infection and transient distal ischemia not resulting in tissue loss, and two episodes of catheter malfunction. In eight (11%) patients, signs of distal vascular insufficiency developed shortly catheter placement and resolved after catheter removal. The development of this complication correlated significantly (p less than .05) with younger age (5.5 vs. 22.3 months). We conclude that femoral artery cannulation has a high degree of success in very small, critically ill children. It should be considered an acceptable alternative to small-vessel cannulation when the latter is not technically achievable, or in the unstable patient where rapid establishment of reliable arterial access is necessary. PMID- 2245612 TI - Cardiac arrhythmias in critically ill patients: epidemiologic study. AB - The general prevalence of cardiac arrhythmias in 2,820 consecutive patients was 78%, ranging from 44% in multiple trauma patients to 90% in primary cardiovascular patients. Patients without recorded arrhythmias (22%, n = 621) were used as control subjects. No clinical group was free from cardiac arrhythmias. Atrial tachyarrhythmias had the highest prevalence in the population as a whole (28%) and in all clinical groups except multiple trauma. Atrial fibrillation was the most common atrial arrhythmia (52%); ventricular arrhythmias followed. Patients with atrial tachyarrhythmias, nodal rhythm ventricular bradyarrhythmias, and ventricular rapid rhythms had significantly (p less than .01) increased mortality rates (40%, 44%, 77%, and 51%, respectively) when compared with patients without arrhythmias (35%). The relative risk of dying (RRD) of these clinical groups was increased by 1.16, 1.27, 2.20, and 1.47, respectively. Patients with cardiorespiratory precipitating disease and any arrhythmia except atrial bradyarrhythmia had a mortality rate between 32% and 74%, significantly (p less than .05) different from that of patients within the same clinical groups without arrhythmias. The RRD was increased by 1.67 to 3.40. Septic patients with atrial tachyarrhythmia or nodal rhythm and neurologic patients with nodal or ventricular arrhythmias also had significantly (p less than .01 and .05, respectively) increased mortality and were at higher RRD (1.53 to 2.81). Our data suggest that severe illness may be present in some clinical groups of critically ill patients with cardiac arrhythmias. PMID- 2245613 TI - Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study. AB - Eighty-four intubated, mechanically ventilated patients were prospectively evaluated for incidences of colonization and nosocomial pneumonias dependent on whether they received endotracheal suctioning by an "open" suction method vs. "closed" suction (Trach Care Closed Suction System) method. Results show that closed suctioning is associated with a significant (67% vs. 39% p less than .02) increase in colonization compared with open suctioning. However, difference in the incidence of nosocomial pneumonia was not significantly (26% vs. 29%) different between closed and open suctioning. Differences in severity of illness (Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention Scoring System), age, sex, presence of NG tubes, use of H2 antagonists or antacids, use of antibiotics, and history of smoking were all nonsignificant. Survival analysis demonstrated that the probability of survival without developing nosocomial pneumonia was greater among closed-suctioning patients vs. open-suctioned patients (p less than .03). This study shows that suctioning performed via the Trach Care closed-suction system increases the incidence of colonization but not the incidence of nosocomial pneumonia, and may actually decrease mortality when compared with open-suction systems. PMID- 2245614 TI - Pentoxifylline attenuates edema formation in proteolytic enzyme-induced lung injury. AB - Ex vivo canine lung lobes were exposed to a pancreatic proteolytic enzyme (chymotrypsin) alone or chymotrypsin after pretreatment with a continuous infusion with pentoxifylline. The lobes exposed to chymotrypsin gained 133 g, while the pentoxifylline-treated lobes gained only 65 g (p less than .05) over the 3-h experimental period. These results suggest that pentoxifylline significantly attenuates the lung weight gain associated with chymotrypsin. PMID- 2245615 TI - Platelet-activating factor: evidence against a role in hypoxic pulmonary vasoconstriction. AB - The mechanism of hypoxic pulmonary vasoconstriction (HPV) remains unknown. The platelet-activating factor (PAF) antagonist WEB 2086 attenuated HPV in the isolated lung model of the rat. We evaluated the effect of WEB 2086 on HPV in an intact animal. Pigs were anesthetized, mechanically ventilated, and had their hemodynamic variables monitored with a pulmonary artery catheter and arterial line. Cardiac output was measured by thermodilution. Initial studies determined that PAF (0.03 to 1.0 micrograms) injected iv dose-dependently increased pulmonary vascular resistance (PVR) with a 262 +/- 58% increase in PVR 5 min after a dose of 1.0 microgram. WEB 2086 (25 mg/kg iv) completely blocked the increase in PVR caused by iv PAF. Additionally, indomethacin (2 mg/kg followed by 2 mg/kg.h iv) treatment of the animals attenuated the PAF-induced increase in PVR. To evaluate the effect of WEB 2086 on HPV, animals were alternately ventilated with 21% oxygen and 10-min periods of 10% oxygen to induce HPV. After three initial control episodes of hypoxic ventilation, WEB 2086 (25 mg/kg) was injected iv and two more episodes of ventilation with 10% oxygen were given. During the three control HPV episodes the increases in PVR were 80 +/- 10%, 108 +/- 10%, and 107 +/- 22% (n = 5). After WEB 2086, the increase in PVR during two episodes of hypoxia were 96 +/- 28% and 99 +/- 19%, respectively, which was not significantly different from the control response to hypoxia. We conclude that iv PAF dose dependently increases PVR in pigs, and can be blocked by WEB 2086, that its effect is partially mediated through cyclooxygenase products, and that PAF does not appear to mediate HPV in this species. PMID- 2245616 TI - Effect of calcium entry blocker nitrendipine on renal function after renal vascular occlusion. AB - The ability of the Ca entry blocker nitrendipine to improve postischemic renal function was studied in nine groups (n = 70) of rats. After anesthesia, nitrendipine was administered for 15 min through the femoral vein. The dose administered depended on the group. Group 1 (n = 7), the control, received only 0.9% NaCl, group 2 (n = 12) 0.25 mg/kg; group 3 (n = 10) 0.50 mg/kg; group 4 (n = 8) 0.75 mg/kg; group 5 (n = 6) 1.00 mg/kg; group 6 (n = 7) 1.50 mg/kg; group 7 (n = 7) 2.00 mg/kg; group 8 (n = 6) 2.50 mg/kg; and group 9 (n = 7) 3.00 mg/kg. After the administration of nitrendipine, the kidneys were rendered ischemic for one hour by cross-clamping the renal vessels. Comparison of 24-h creatinine clearances for 72 h after reversal of ischemia demonstrated that nitrendipine was capable of providing a degree of protection against renal ischemia and the protective effect was dose dependent (p less than .05). PMID- 2245617 TI - Endotoxin does not directly alter norepinephrine release or vasoactivity in dog pulmonary artery and portal vein. AB - The direct effect of Escherichia coli endotoxin on the release of norepinephrine (NE) and the contractile response consequent to the release of NE were studied in isolated, superfused segments of dog pulmonary artery and portal vein during resting conditions and during electrical stimulation (ES). High-pressure liquid chromatography with electrochemical detection was used to quantify the endogenous NE released and that remaining in the tissue after stimulation. Endotoxin (1 micrograms/ml and 10 micrograms/ml in superfusate) had no effect on the release of NE from either pulmonary artery or portal vein. Endotoxin also had no effect on vasoactivity in response to ES. Thus, in isolated pulmonary artery and portal vein, endotoxin, in the doses employed, does not directly affect release of NE from adrenergic nerve endings, nor does it affect the sequence of events that starts with transmitter-receptor interaction and ends with contraction of smooth muscle cells. PMID- 2245618 TI - Continuous, in vivo pulmonary venous admixture from fiberoptically measured hemoglobin saturations. AB - In six anesthetized swine, pulmonary venous admixture (Qsp/Qt) was calculated by four methods: a) Qsp/Qt 1, fiberoptically measured arterial and mixed venous Hgb saturation (SaO2 and SvO2), PaO2 and PvO2 derived from saturations; b) Qsp/Qt 2, fiberoptically measured SaO2 and SvO2, PaO2 and PvO2 measured by blood gas analysis; c) Qsp/Qt 3, PaO2 and PvO2 measured by blood gas analysis, SaO2 and SvO2 derived from tensions; d) Qsp/Qt 4, SaO2 and SvO2 measured by bench oximetry, PaO2 and PvO2 derived from saturations. Input from the fiberoptic catheters was fed into a computer programmed to calculate Qsp/Qt 1 every 20 sec. Fifty-eight of these values were compared with simultaneously calculated Qsp/Qt 2, 3, and 4. There was no difference between fiberoptic and derived SaO2 or fiberoptic and cooximetric SvO2. Correlations and slopes for Qsp/Qt 1 with Qsp/Qt 2, 3, and 4 were significant (p less than .05). Comparing mean differences, Qsp/Qt 1 was significantly different only from Qsp/Qt 3 (p less than .01). We conclude that dual oximetry reliably tracks Qsp/Qt. PMID- 2245619 TI - Endotracheal tube cuff pressure assessment: pitfalls of finger estimation and need for objective measurement. AB - Estimation of endotracheal (ET) cuff pressure by finger palpation is one of the methods currently used in the clinical setting. We compared the accuracy of this method with instrumental intracuff pressure measurement in tracheal model tests by 20 members of our ICU team. Four different ET tubes at three different pressure levels were examined. Accuracy for the estimated method by finger palpation was 69% for high pressures, 58% for normal pressures, and 73% for low pressures. We observed differences in terms of sensitivity, specificity, and positive predictive power between different tubes reflecting differences in tube characteristics and interobserver variability. We conclude that precise intracuff pressure measurement is mandatory to prevent complications of over- or underinflation. PMID- 2245620 TI - Intrahospital transport of critically ill patients. AB - Severe complications sometimes occur in critically ill patients during intrahospital transport. Possible causes may be inadequate ventilation, insufficient monitoring, interrupted application of vasoactive drugs, or disconnections and accidental extubation. We constructed a transport unit equipped with a respirator; capnometer; monitor to measure ECG, arterial and intracranial pressures, and temperature; and two syringe pumps that can be connected easily to the patient's bed. Gas is supplied by cylinders with oxygen and air. Electrical power is supplied by two accumulators connected to recharger and transformer devices that deliver 220 V (110 V). Since this transfer unit was introduced, we have had no unanticipated problems during intrahospital ICU patient transport. PMID- 2245621 TI - Prototype volume-controlled resuscitator for neonates and infants. AB - Twenty-five infants receiving assisted ventilation in an ICU were manually ventilated for 5-min periods using either a new prototype volume-controlled resuscitator (VCR) or a standard self-inflating resuscitator (SIR). Variables monitored during these 5-min periods included heart rate, respiratory rate, mean arterial pressure, mean airway pressure (Paw), end-tidal CO2 (PetCO2), pulse oximetry oxygen saturation, PaO2, and PaCO2. Significant differences in posttrial values for the following variables were: a) PetCO2 (31.2 +/- 9.1 vs. 25.6 +/- 8.2 torr, p less than .001); b) PaCO2 (38.0 +/- 4.9 vs. 33.2 +/- 6.7 torr, p less than .01); and c) pH (7.4 +/- 0.6 vs. 7.5 +/- 0.1, p less than .04) at comparable Paw (9.5 +/- 7.6 vs. 8.0 +/- 6.0, NS). Eighty-four percent (21/25) of infants in the VCR group had normal PaCO2 values (35 to 45 torr) while only 44% (11/25) in the SIR group achieved normocarbia (p less than .001). Measurements of the highest (Pmax) and lowest (Pmin) inspiratory pressure (cm H2O) in 15 patients demonstrated marked variation in Pmax with the SIR. Differences in Pmax (SIR minus VCR) were significant (10.8 +/- 3.7, p less than .02) but not in Pmin (0.5 +/- 3.5, NS). Our study demonstrates that ventilation with the VCR resulted in less hyperventilation with minimal pressure variability as compared with the SIR. Further studies in the neonate are warranted. PMID- 2245622 TI - Consensus report on the ethics of foregoing life-sustaining treatments in the critically ill. Task Force on Ethics of the Society of Critical Care Medicine. PMID- 2245623 TI - Risks of human immunodeficiency virus infection to patients and healthcare personnel. AB - The risk of nosocomial human immunodeficiency virus (HIV) infection among hospitalized patients comes almost exclusively from transfusion of fresh blood products. Current estimates of the risk of HIV infection from the transfusion of blood or components vary from 1/40,000 to 1/250,000 (0.0025% to 0.0004%), with the most probable likelihood estimated to be 1/153,000 (0.0007%). The major route of transmitting such HIV infection is via blood collected during the interval between infection of the donor and development of a detectable circulating antibody level to the AIDS virus (i.e., the "window period"). The current risk to hemophiliacs receiving treated coagulation factor concentrates is negligible. The risk to healthcare personnel of acquiring HIV infection from accidental puncture wounds and from handling HIV-infected blood or body fluids is 0.42% per episode. Most reported seroconversions have resulted from penetrating injuries with sharp objects contaminated with HIV-positive blood. The degree of risk to healthcare workers will vary with the community, the patient population served, and the frequency of penetrating injuries. PMID- 2245624 TI - Clinical trials of selective decontamination of the digestive tract: review. PMID- 2245625 TI - Critical Care Fellowship graduates--1991. PMID- 2245626 TI - Management of the transurethral prostate resection syndrome: time for reappraisal? PMID- 2245627 TI - Benzodiazepine withdrawal syndrome after a benzodiazepine antagonist. PMID- 2245628 TI - Intracranial pressure monitoring in acute disseminated encephalomyelitis in childhood. PMID- 2245629 TI - Coming of age and changing of the guard. PMID- 2245631 TI - "New and improved" scoring systems. PMID- 2245630 TI - Acute lung injury and pentoxifylline. PMID- 2245632 TI - Invasive blood pressure arterial monitoring in brain death organ donor. PMID- 2245633 TI - Pulmonary capillary pressures during hypoxia and hypoxemia. PMID- 2245634 TI - Amrinone pharmacokinetics in neonates and infants. PMID- 2245635 TI - High doses of epinephrine. PMID- 2245636 TI - More on the use of intrinsic positive end-expiratory pressure. PMID- 2245637 TI - Use of transtracheal catheter for treatment of hypoxic respiratory failure when mechanical ventilation was refused. PMID- 2245638 TI - Zezuru turn of the screw. On children's exposure to evil. AB - Zezuru adults and children take into account concepts of evil in directing their lives, especially in managing incidents of trauma and sickness. Using the story The Turn of the Screw by Henry James to reflect on these notions, evil is traced in the expressions heard and treatment sessions witnessed during two years research with 60 traditional healers in Mashonaland, Zimbabwe. Evil, particularly as evidenced in witchcraft and possession by aggrieved spirits, is part of a discourse on human suffering--illness, misfortune, death--within a specific community. Healers' treatment of children and their conceptions of childhood form the base for a discussion of evil. PMID- 2245639 TI - Possessed and dispossessed youth: spirit possession of school children in northwest Madagascar. AB - Spirit possession is a common experience shared by many women in northwest Madagascar. In the town of Ambanja, possession by volatile and dangerous Njarinintsy spirits is an affliction which strikes young, adolescent schoolgirls. When Njarinintsy is contrasted with tromba, another well-known class of spirits found in this region, it becomes clear that Njarinintsy possession is a relatively recent phenomenon, and its victims form a discrete and unusual group. These girls are, in essence, young migrants, who have moved alone to town in order to attend school. Close examination of their experiences reveals that these young girls must cope, on their own, with the conflicts and contradictions that plague the shift from rural to town life, and from youth to adulthood. Such problems are further complicated by those associated with educational policy in Madagascar. These children, more than any other members of this community, suffer from the contradictions of a fragmented world. Possession provides them with a means through which to express the chaos inherent in their daily lives. PMID- 2245640 TI - Indignant suicide in the Pacific: an example from the Toraja Highlands of Indonesia. AB - This paper describes and analyzes a type of Toraja (South Sulawesi, Indonesia) suicide in which a person kills him or herself after having been slighted or offended, usually by a close family member. Comparing and contrasting such suicides to similar types found elsewhere in Austronesia-speaking Oceania, the paper argues that self-inflicted deaths of this nature are not so much 'anomic,' as suggested by some analysts, as 'indignant'; they are committed by persons who feel that they have been severely mistreated or abused according to traditional notions of reciprocity, mutual aid, and the dangers of frustrated desire. The paper concludes by suggesting that Durkheim may have underestimated the frequency and importance of 'indignant' suicide in 'traditional' societies and that, conversely, contemporary analysts may be underestimating the importance of traditional norms and values in accounting for the high rates of suicide found in many parts of the Pacific today. PMID- 2245641 TI - Psychiatric case finding in Ethiopia: shortcomings of the Self Reporting Questionnaire. AB - Attenders of health care facilities usually present somatic complaints. It is important to identify the psychiatric patients among them, especially the neurotic complainers. They are at risk for being exposed to expensive somatic investigations and being prescribed useless and sometimes harmful drug treatment. The World Health Organization designed the Self Reporting Questionnaire (SRQ), to be a universally applicable psychiatric case finding instrument, for use in medical clinics. A feasibility study with this instrument was carried out with 110 respondents in Ethiopia. A moderate criterion validity was found, limitations being partly due to the sensitivity of the SRQ to help-seeking behavior, even in the absence of any mental illness. This study also revealed problems in transcultural communication because many of the diagnostic concepts used in this instrument were too western to be transposed unchanged to the Ethiopian culture. Items need fairly extensive modification to be applicable there. PMID- 2245642 TI - Explanatory models of major depression and implications for help-seeking among immigrant Chinese-American women. AB - This study explores the explanatory models of major depression in a group of 40 recently immigrated Chinese-American women, and demonstrates the significant relationship between problem conceptualization and help-seeking behavior. Respondents are presented a vignette depicting major depression, from which they are asked to conceptualize the problem described and answer questions regarding its cause, impact and potential sources for help-seeking. Those who provide a psychological conceptualization are likely not to suggest professional services, but to turn to themselves and family and friends for assistance. On the other hand, those who hold a physical conceptualization are likely to seek out medical services. Implications for effective mental health service delivery to this population are discussed. PMID- 2245643 TI - On the composition and origin of the urea-soluble polypeptides of the U18666A cataract. AB - The composition and origin of the urea soluble polypeptides which accumulate in the U18666A rat-cataract were studied. Chromatography on Sephacryl S-200 in 7.2 M urea separated the USP into 19-20 and 22-26 kDa enriched fractions. The polypeptide composition of these fractions was probed by immunoblotting of IEF and 2-D electrophoresis gels. The cataract USP largely focused at pHs comparable to alpha- and beta-crystallins. Immunoblotting of 2-D gels showed the USP to be composed predominantly of alpha- and beta-derived crystallins; little gamma polypeptide was detected in the gels. Some of the insoluble alpha-crystallin appeared to be degraded. Changes in the lens WSP which accompanied the increase in USP were also measured. WSP decreased more than USP increased. Decreases in soluble high molecular weight proteins (alpha- plus beta-crystallins) and medium molecular weight proteins (beta-crystallins) were calculated which together could entirely account for the increased USP. An unexpected decrease in the lens soluble low molecular weight proteins (gamma-crystallins) appeared largely due to the selective leakage of gammas from the lens. The protein content of the ocular humors from eyes with cataracts increased 4 fold and contained polypeptides that focused on IEF like gamma-light crystallin and reacted with the gamma-crystallin antiserum. The cause of the protein insolubilization in the U18666A cataract is unknown but could be partially due to increased aggregation of alpha-crystallins secondary to loss of gamma-crystallins from the lens. PMID- 2245644 TI - L-alpha-glycerophosphate binding to bovine gamma-crystallin: a potential link between metabolism and supramolecular order. AB - The highly selective nature of protein-ligand interactions provides a sensitive mechanism for the modulation of cellular activity by proteins. In the eye lens the supramolecular order of the lens crystallins, which is expected to be susceptible to protein electrostatic charge, in part defines transparency. The binding of charged ligands to proteins is one way of achieving an alteration in protein electrostatic charge. Evidence is presented that L-alpha glycerophosphate, a major phosphorus metabolite of eye lens metabolism, binds to the globular protein, gamma-crystallin with moderately high affinity and in a positive cooperative manner. The following binding parameters were obtained from equilibrium measurements: minimum number of binding sites, n = 2; Kassoc = 6.2 +/ 0.5 x 10(3) M-1; cooperativity parameter, alpha H = 1.9 +/- 0.1. Interactive computer graphics display techniques were used to locate putative ligand binding sites, and in turn, to identify the possible molecular interactions responsible for the binding of ligand to protein at one of the sites. One putative binding site was located in the cleft between the two domains of gamma II-crystallin. Arginyl residues 79 and 147 are involved in ligand binding as are the peptide carbonyl oxygens of residues Tyrosyl-50 and Aspartyl-156. Five hydrogen bonds between the ligand and the protein structure are predicted for the binding of L alpha-glycerophosphate, whereas only 3 occur for the binding of the "unnatural" D enantiomorph. Modulation of both lens protein supramolecular organization and lens metabolism is predicted to be a consequence of L-alpha-glycerophosphate binding to gamma-crystallin in the lens. PMID- 2245645 TI - Cornea derived neutrophil chemotactic factors: intracellular synthesis and release. AB - The present study was designed to test the hypothesis that the release of neutrophil chemotactic factors (NCF) from isolated corneas following hydrogen peroxide stimulation requires specific intracellular synthesis. For these studies, the epithelial surfaces of isolated rabbit corneas were preincubated with various inhibitors of protein synthesis (cycloheximide, 10 micrograms/ml, and puromycin, 50 micrograms/ml) and transcription (actinomycin D, 5 micrograms/ml) for 60 min prior to exposure of the corneas to glucose (G, 1 mg/ml) and glucose oxidase (GO, 20 U/ml) for 6 h at 37 degrees C. All three inhibitors decreased the levels of NCF recovered in the extracorneal fluids by 80 98%, suggesting that peroxide acts to upregulate NCF production at both the transcription and translation levels. When corneas were incubated with G/GO for 6 h at 12 degrees C or 4 degrees C instead of 37 degrees C, a reduction in the levels of NCF recovered in the supernatants was noted at 12 degrees C (46-91% inhibition) and at 4 degrees C (67-96% inhibition), suggesting that the synthesis of NCF at cold temperature was only reduced but not totally inhibited. To demonstrate that the observed reduction in chemotactic activity recovered from corneas incubated at 12 degrees C or 4 degrees C is not due to a temperature dependent inhibition of NCF biosynthesis, but rather to a disruption of intracellular vesicular transport, temperature shift experiments were performed. Corneas were incubated with G/GO overnight at 12 degrees C or 4 degrees C prior to shifting to 37 degrees C for an additional 6 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245646 TI - A maxi calcium-activated potassium channel from chick lens epithelium. AB - The apical membrane of embryonic chick lens epithelium contains at high density, a large conductance K+ channel whose open probability is increased by Ca++ at the inner surface of the membrane and by depolarization. The conductance of the channel when it is fully open in symmetrical 150 mM K+ solutions is 214 +/- 3 pS (mean +/- std. error). The current through the channel is a function of the K+ concentration. Gating (open probability) at positive transmembrane voltages increases as the internal [Ca++] is raised above 10(-7) M. The open probability decreases monotonically as the transmembrane voltage is made more negative. The channel is at least 87 times more permeable to K+ than to Na+ or Li+ and shows appreciable permeability to Rb+ and NH4+. It has at least three subconductance levels amounting to approximately 3/4, 1/2, and 1/4 the fully open unitary conductance. The occurrence of these subconductance levels is highly variable from one patch to another. The channel is blocked by physiological levels of internal Na+ but not over a physiological voltage range. This block is partially overcome by elevated external K+. This K+ channel from chick lens epithelium is blocked by a number of compounds known to block BK channels in other tissues. Here we show that decamethonium and Ba++ are effective blockers when added to the inner bathing solution at concentrations greater than .1 mM. Tetraethylammonium, Cs+, quinine, quinidine and Ba++ are all effective blockers when applied to the outer side of the channel in the .1 mM - 5 mM range. With the exception of internal Ba++, all of these compounds produce a fast flicker-type blockade. We use a one-site model to quantify the blockade caused by these flicker producing agents. The voltage dependence of the blockade by Cs+ suggests that this channel probably allows multiple occupancy. PMID- 2245647 TI - Effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow in the cynomolgus monkey. AB - The effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow were investigated in cynomolgus monkeys, with a labeled albumin dilution method. The maximal increase in aqueous humor flow caused by intracameral (100 micrograms/ml) or intravenous (0.4 micrograms/kg/min) administration of terbutaline was about 100%. The effect of intravenously infused terbutaline was completely abolished by intracameral administration of timolol, 0.1 mg/ml. The same dose of timolol also abolished the effect of intravenously infused VIP, 50 ng/kg/min. Intravenous administration of timolol, 0.2 mg/kg, had no effect on VIP-stimulated aqueous humor flow, when VIP (90 micrograms) was given intracamerally, but abolished completely the effect of intracameral terbutaline, 100 micrograms/ml. The results suggest that the effect of intravenously infused VIP on aqueous humor flow is secondary to activation of the sympathetic nervous system, while the effect of intracameral administration of VIP is a direct effect on the ciliary epithelium. The maximal aqueous humor flow achieved with terbutaline is comparable to that in conscious cynomolgus monkeys. PMID- 2245648 TI - Cysteine and glutathione metabolism in organ-cultured rat corneas. AB - The capability of organ-cultured rat corneas to metabolize cysteine and synthesize glutathione was assessed by use of radioactive L-cyst(e)ine. Metabolites from protein-free tissue extracts were separated and quantified by HPLC, using radioisotope and ultraviolet detectors. Most of the radioactivity detected in the rat cornea was found in three areas of the HPLC elution profile: 1) reduced glutathione, 2) cystine and 3) in a rapidly eluting area (the 'five minute' area) consisting of several unidentified peaks. The proportion of radioactivity found within the five-minute area increased with time of incubation and became the dominant radioactive peak area by 48 hours of incubation. In contrast to rat lens extracts, the synthesis of glutathione in rat cornea formed a minor portion of the L-cysteine metabolic products. The unlabeled reduced glutathione concentration was relatively stable over a 48-hour incubation period. Synthesis of glutathione was prevented by 0.3 mM buthionine sulfoximine, resulting in more than 90% of the radioactivity being contained in the five minute peak area. Inhibition of glutathione synthesis allowed the estimation of glutathione's half-life to approximate 10.5 hours in the organ-cultured rat cornea. PMID- 2245649 TI - Induction of stress (heat shock) protein 70 and its mRNA in rat corneal epithelium by hyperthermia. AB - Because stress proteins are believed to play an important role in cellular repair and survival mechanisms, we investigated accumulation of the 70-kilodalton stress protein (SP70) and its mRNA in the rat corneal epithelium after hyperthermia. In the corneal epithelium of control rats, in situ hydridization with a radioactive probe for SP70 mRNA followed by autoradiography revealed very few silver grains. Eighteen hours after the rats were subjected to hyperthermia, the density of silver grains was greatly increased and this elevated level of corneal epithelium SP70 expression continued through 50 hours after heat treatment. Immunostaining for SP70 in the corneal epithelium was consistent with the in situ hybridization, being weak and mainly confined to the basal cells in control rats and increasing by 18 hours in the heat-treated rats. At 50 hours post-heat treatment, the immunostaining was denser than control in all corneal epithelial cells, especially in the apical portions of the basal and wing cells. These results suggest that SP70 may be an important factor in the response of the corneal epithelium to adverse environmental changes. PMID- 2245650 TI - Serum-free culture of porcine and rabbit corneal epithelial cells. AB - To better define the growth requirements for corneal epithelial cells, methods for serum-free culture were established. Sheets of corneal epithelium from eyes of swine and rabbits were obtained by dispase treatment of corneal buttons, and single cells and small clumps were obtained by further dissociation with trypsin/EDTA. Growth of cells with epithelial-like morphology was readily achieved in low calcium MCDB 153 medium containing epidermal growth factor, insulin, hydrocortisone, and bovine pituitary extract. Primary cultures could be subcultivated at least four times at 1:6 split ratios. Examination of cultured corneal epithelial cells by transmission electron microscopy demonstrated a relatively undifferentiated phenotype. Elevation of calcium in the medium caused the reappearance of desmosomal junctions and a more typical corneal epithelial morphology. PMID- 2245651 TI - Mycosis fungoides and the Sezary syndrome: pathology, staging, and treatment. AB - Mycosis fungoides and the Sezary syndrome are forms of cutaneous T-cell lymphoma. Mycosis fungoides is an uncommon disease: only about 500 new cases are diagnosed in the United States annually. The median age of onset is 55 years and there is a 2:1 male predominance. The etiology of mycosis fungoides is unknown. Although occupational exposures have been implicated, case control studies fail to support this hypothesis. Mycosis fungoides is typified by cutaneous plaques which may evolve into tumors over the course of time. It is often preceded by a lengthy pre mycotic phase prior to the time of definitive diagnosis. In its earliest diagnostic phase, there may only be slightly scaling patches with a limited distribution. Indurated lesions evolve into plaques, which may become more generalized in their distribution. As the severity of skin involvement increases, there is an increasing likelihood of spread to extracutaneous sites. The pathology of this disease is marked by involvement of the epidermis (Pautrier microabscesses). Immunologic studies characterize these cells as belonging to the helper T-cell subset. Genotypic analysis demonstrates monoclonal rearrangements of the T-cell receptors of the infiltrating cells. The staging system for mycosis fungoides considers the extent of skin involvement, presence of lymph node or visceral disease, and detection of abnormal cells in the peripheral blood. Patients with disease limited to the skin (90% of newly diagnosed cases) are treated best with topical or cutaneous therapies. Common modalities include psoralen photochemotherapy (PUVA), topical chemotherapy (nitrogen mustard) and total skin electron beam therapy. Both topical nitrogen mustard and electron beam therapy have good initial response rates (73% and 100%) and may achieve long-term disease-free survival, especially in patients with initially limited disease. Even if the response is incomplete or relapse occurs, substantial and very important palliation is generally achieved with topical therapy. Recurrent or resistant cutaneous disease will require the use of sequential topical treatment. The median survival time of patients who present with disease limited to the skin is greater than 10 years, and many deaths in this group are from intercurrent causes, especially in patients with limited or generalized plaque disease. If cutaneous tumors are present, the majority of these patients will eventually die from disease-related causes. The prognosis of patients who develop extracutaneous disease is exceedingly poor (median survival time, approximately 1 year).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2245652 TI - Cardiac involvement in AIDS. AB - Cardiac involvement in AIDS may occur at any stage of HIV disease and may manifest as congestive cardiomyopathy, potentially lethal arrhythmia, or pericardial effusion and tamponade. The heart may be affected by nearly all of the opportunistic infections and many of the malignancies associated with the syndrome. Although often clinically unobtrusive, cardiac lesions may be important in the pathogenesis of significant clinical symptoms and play an often unrecognized role in the prognosis and natural history of AIDS. PMID- 2245653 TI - Transesophageal echocardiography. PMID- 2245654 TI - Psychosocial aspects of ambulatory pediatrics. AB - The ability to interview is an essential skill that continues to develop throughout a pediatrician's professional life. Interviewing is a complex procedure that requires in-depth understanding of medical illness, child development, individual and family dynamics, cultural variations, and self awareness--your personal values and response to crisis, serious illness, and stress. Interviewing is learned by thoughtful reflection of each interview as well as more formally through the use of videotape and attending observation. Each interview is an opportunity to develop a relationship and add a bit of experience that is unique to the patient or parent and potentially useful in understanding more in the future. Although this procedure receives little formal attention, the interview is often the primary vehicle for making the diagnosis, relating to the child and family, and easing emotional suffering and can be a source of satisfaction for the many hours of hard work. PMID- 2245655 TI - Na(+)-Ca2+ exchanger: the elusive protein. PMID- 2245656 TI - Circulating extracellular matrix components as markers for connective tissue response to inflammation. A clinical and experimental study with special emphasis on serum aminoterminal type III procollagen peptide in rheumatic diseases. PMID- 2245657 TI - Bias in double-blind trials. PMID- 2245658 TI - Gallstones. An epidemiological investigation. PMID- 2245659 TI - Selenium-induced growth retardation. Histochemical and endocrinological studies on the anterior pituitaries of selenium treated rats. PMID- 2245660 TI - Gastroplasty and very-low-calorie diet in the treatment of morbid obesity. PMID- 2245661 TI - The medical component in fact-finding missions. AB - Fact-finding missions (FFMs) are useful instruments in examining allegations of human rights violations. The United Nations Convention against Torture and other Cruel Inhuman or Degrading Treatment and the European Convention for the Prevention of Torture and Inhuman and Degrading Treatment or Punishment include the possibility for FFMs. The role of the medical profession in FFMs is discussed, and it is recommended that doctors should be included in FFMs to document allegations of torture and other human rights abuses. PMID- 2245662 TI - Interferon alpha-2b dependent recalcitrant genital warts. AB - Aggressive and chronic disfiguring large penile warts, where previous treatment had been unsuccessful, were flattened in a non-immunocompromised patient treated with interferon alpha-2b 5 x 10(6) I.U. subcutaneously three times a week. Cessation of therapy resulted in rapid recurrence of lesions, indicating persistence of the viral infection. Systemic interferon therapy, however, was the only remedy that could suppress the disease. Only transient and mild systemic toxicity was observed. Subcutaneously injected interferon alpha-2b should be considered in patients with otherwise therapy resistant large or disseminated genital warts. PMID- 2245663 TI - Prescribing in hospital outpatient departments and rural health facilities in Uganda: some clinical and educational implications. AB - A comparison of prescribing patterns in hospital outpatient departments (OPD) and rural health units (RHU) in Uganda revealed an average of 2.45 and 1.66 drugs prescribed per treatment episode in OPD and RHU respectively. 40.1% of the OPD and 57.3% of the RHU prescriptions included antibacterials. It is argued that in view of the relevant morbidity pattern, an average of 1.4-1.5 drug/treatment episodes, as well as 15-20% receiving antibacterials would seem appropriate, thus leaving scope for considerable cost reductions. A successful strategy for achieving rational prescribing is likely to include a variety of educational approaches aimed at all present and future prescribers. PMID- 2245664 TI - Does pulmonary artery catheterization benefit patients with acute myocardial infarction? PMID- 2245665 TI - Making bronchoscopy count. PMID- 2245666 TI - Surgical treatment of obstructive sleep apnea. Is mandibular surgery an advance? PMID- 2245667 TI - Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics. Does aminophylline add any benefit? AB - STUDY OBJECTIVE: To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma. DESIGN: Randomized, double-blind, placebo-controlled trial throughout the study. SETTING: University Hospital Clinical Research Center. PATIENTS: Forty-four patients admitted from the emergency room with a primary diagnosis asthma; 39 patients completed the study. INTERVENTIONS: Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol; prednisone 0.5 mg/kg body weight every 6 h orally; and supplemental oxygen. Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml. Changes were made in placebo infusion rates to maintain the double blind design. MEASUREMENTS AND RESULTS: Forced expiratory volume in 1 s (FEV1) and other spirometric measurements every 8 h by a blinded investigator or trained respiratory therapist. Subjective patient response and duration of hospitalization were compared. No difference in spirometric measurements was observed between the two groups at any time point. On admission to the study, FEV1 in the placebo group was 41.5 (+/- 2.9) percent predicted and in the aminophylline group 34.7 (+/- 2.3) percent predicted (p = 0.08). At discharge, FEV1 was 70.4 (+/- 2.9) percent predicted in the placebo group and 63.7 (+/- 2.8) percent predicted in the theophylline group (p = 0.10). There was no difference in subjective patient rating or duration of hospitalization between the two groups (placebo 1.95 days and aminophylline 1.78 days, p = 0.51). CONCLUSIONS: Our results suggest that aminophylline therapy does not add significant benefit to other standard therapies in hospitalized adult asthmatic patients. Because of the risks and cost of aminophylline treatment in the hospital setting, further research is needed to determine if there are subgroups of adult asthmatics who may benefit from the addition of aminophylline to other standard optimal therapies. PMID- 2245668 TI - Utility of fiberoptic bronchoscopy in nonresolving pneumonia. AB - Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series. PMID- 2245669 TI - Fiberoptic bronchoscopy without premedication. A retrospective study. AB - The objective of this study was to determine if flexible FOB could be performed safely without premedication other than topical anesthesia. A total of 281 procedures performed during a 12-month period at a VA medical center were reviewed. Ninety-one procedures performed without premedication were compared with 190 procedures performed with premedication. Complications occurred in 5 percent of patients in each group. Statistical analysis revealed no significant differences in age, spirometry, P(A-a)O2 or SaO2 between both groups. Despite the proven safety of outpatient FOB without sedation, many bronchoscopists administer complicated premedication regimens and employ ambulatory surgery beds or recovery rooms to monitor patients before and after procedures. These results support a simplified approach to routine FOB which would include no premedications and greater use of outpatient facilities resulting in decreased expenditures without compromising patient care, safety or comfort. PMID- 2245670 TI - Use of pulmonary artery catheters in patients with acute myocardial infarction. Analysis of experience in 5,841 patients in the SPRINT Registry. SPRINT Study Group. AB - This study analyzes the use of PAC in a registry comprising 5,841 hospitalized patients with AMI. A total of 371 patients received PAC. In-hospital mortality was higher in patients with CHF who received PAC, while there was no difference in patients with cardiogenic shock or persistent hypotension. Mortality in patients receiving PAC was higher irrespective of the presence or absence of "pump failure." A separate analysis of discharge summaries of 364 patients with CHF showed that PAC was used more frequently in sicker patients and that when severity of CHF was assessed, no difference in mortality was found in patients with mild or moderate CHF. We conclude that while a higher in-hospital mortality is found in patients receiving PAC, this excess is likely related to difference in severity of CHF, which had not been assessed in every individual. It is unlikely that PAC increases mortality. PMID- 2245671 TI - Acute lobar atelectasis. A comparison of two chest physiotherapy regimens. AB - Fourteen cases of acute lobar atelectasis were alternately allocated to one of two chest physiotherapy regimens for treatment. Treatment in group 1 comprised positioning, vibrations, hyperinflation, and suction, and in group 2, treatment consisted of hyperinflation and suction alone. Treatment in either group was given hourly for six hours. Patients in group 1 had a significantly higher mean percentage resolution of their atelectasis (mean value, 60.1 percent), as seen on chest roentgenogram, after one treatment intervention than patients in group 2 (mean value, 7.6 percent; p less than .006). After the intensive six-hour treatment period, the difference between the groups was marginally statistically significant, still favoring group 1 over group 2 (p less than .055). Follow-up roentgenograms at 24 and 48 hours revealed no significant difference between the treatment groups (p greater than .10 and greater than .20, respectively). These results suggest that, at least initially in the course of acute lobar atelectasis, positioning and vibrations add to the efficacy of a treatment of hyperinflation and suction alone. PMID- 2245672 TI - A limited diagnostic investigation for obstructive sleep apnea syndrome. Oximetry and static charge sensitive bed. AB - A simplified sleep apnea investigation consisting of combined oximetry and respiration movement monitoring was compared with conventional polysomnography. These two types of recordings were performed simultaneously during one night in 77 patients with suspected obstructive sleep apnea syndrome (OSAS). A static charge sensitive bed (SCSB) was used in the simplified recording because it provides a comfortable and reliable means of recording respiration movements. Periods of obstructive apneas gave a diamond-shaped periodic respiration movement pattern in the SCSB, usually accompanied by repetitive oxygen desaturations. The average number of desaturations greater than or equal to 4 percent per sleeping hour was termed the oxygen desaturation index (ODI) and compared with the apnea index (AI). In the whole population they were well correlated (p less than 0.0001, R2 = 0.41), but in individual cases there were considerable discrepancies. Patients with periodic respiration movements less than 18 percent of total sleeping time and ODI less than 2 never had AI greater than or equal to 5, whereas patients with periodic respiration greater than 45 percent and ODI greater than 6 always had AI greater than or equal to 5. Fifty-one of the 77 patients fulfilled these criteria. A bradycardia response to apneas was absent in 29 percent of patients with AI greater than or equal to 5. A combination of respiration movement and oximetry recording thus seems to give sufficient information to confirm or negate a diagnosis of OSAS in a majority of patients with clinical symptoms. In borderline patients, further investigations should be performed. PMID- 2245673 TI - Diagnostic value of maximal exercise tidal volume. AB - Though breathing pattern is frequently analyzed during clinical exercise testing, there is little information regarding its usefulness in the differential diagnosis of impaired exercise tolerance. This study tested the hypothesis that differences in peak tidal volume during exercise between patients with different cardiorespiratory diseases are related largely to differences in severity of respiratory mechanical impairment (vital capacity), not to differences in disease state. Patients with chronic obstructive pulmonary disease, restrictive lung disease, bronchial asthma, and heart disease (mitral valve disease or left ventricular dysfunction) were studied. Subjects selected had one and only one of the above diagnoses. All subjects performed maximal (symptom-limited) incremental exercise on a cycle ergometer. Multiple linear regression of all subjects (n = 30) in all four groups showed a significant correlation between VTmax and VC: VTmax = 0.55, VC -0.09 L (r = 0.827, p less than 0.0001). The VTmax/VC (x 100) was (mean +/- SD) 44 +/- 15, 54 +/- 11, 56 +/- 11, and 54 +/- 12 for the COPD, RLD, BA and HD patients respectively. There was no significant difference between any of the groups. We concluded that differences in VTmax between different patients are related largely to differences in VC (ie, differences in severity of respiratory mechanical impairment), not to differences in disease state. Measurement of VTmax or the VTmax/VC ratio has little value in the differential diagnosis of exertional dyspnea. PMID- 2245674 TI - Predicting the need for hospitalization in children with acute asthma. AB - In an attempt to identify factors which influence the decision of physicians to admit patients with acute asthma to the hospital, we studied prospectively 200 children (age 5.6 +/- 3.1 years, mean +/- SD) presenting to our emergency room with acute asthma. The children were assessed on arrival, and on disposition from the Emergency Room by one of the investigators. After obtaining historic data, a clinical score was assigned, and oxygen saturation and pulmonary function were measured. Of the 134 (67 percent) children who were discharged home from the Emergency Room, five returned within seven days and one was subsequently admitted. The clinical score on disposition was the sole variable found to best predict the decision for hospitalization (sensitivity 73 percent, specificity 95 percent). Of the variables obtained at presentation, the resulting decision tree found the clinical score to predict the decision for hospitalization (sensitivity 79 percent, specificity 75 percent). When the individual components of the clinical score were analyzed, the degree of dyspnea, as assessed by the investigator, was chosen as the rule to predict the hospitalization decision (sensitivity 88 percent, specificity 71 percent). We conclude that the decision with respect to the need for hospitalization in acute childhood asthma, is in practice based mainly on careful clinical evaluation. Pulmonary function and SaO2 measurements, although helpful adjuncts in the assessment of acute asthma, do not appear to contribute to the identification of patients who need hospital admission. PMID- 2245675 TI - Systemic hypertension in sleep apnea syndrome. Relationship with sleep architecture and breathing abnormalities. AB - To examine the possible relationship between systemic HT and SAS we compared 21 hypertensive (HT+) and 29 normotensive (HT-) patients for morphologic characteristics, sleep disturbances and respiratory events monitored during a full night polysomnography. There was no significant difference between HT+ and HT- patients with respect to age, weight, BMI, sleep stage distribution and disorganization, apnea-hypopnea index (number of episodes per hour of sleep) and duration (minutes per hour of sleep) nor O2 saturation indices: mean nocturnal and minimum O2 saturation. We conclude therefore that HT in SAS patients is not directly related to morphologic characteristics, sleep disturbances and breathing abnormalities. PMID- 2245676 TI - Atypical presentations of Pneumocystis carinii pneumonia in patients receiving inhaled pentamidine prophylaxis. AB - Inhaled pentamidine is used commonly to prevent Pneumocystis carinii pneumonia (PCP) in patients with advanced human immunodeficiency virus infection. Case reports indicate that PCP can recur in patients who receive inhaled pentamidine and that clinical features may be atypical. To determine the magnitude of this problem, we reviewed retrospectively the medical records of patients with proven PCP during a 30-month period at two hospitals. Four (31 percent) of 13 patients with previous PCP who received inhaled pentamidine prophylaxis had recurrent P carinii infection, including one patient with widely metastatic extrapulmonary disease. Chest roentgenographic findings included cavities, pneumothoraces, bilateral and upper lobe interstitial infiltrates, and pleural effusion. False negative bronchoalveolar lavage and induced sputum examinations were frequent. We conclude that recurrent PCP in patients maintained on a regimen of inhaled pentamidine prophylaxis occurs frequently, causes chest roentgenographic abnormalities other than interstitial infiltrates, and may be difficult to diagnose. Clinicians who choose to use this effective and convenient mode of prophylaxis should be aware of the problems attendant to its use. PMID- 2245677 TI - Serum lidocaine concentrations in children during bronchoscopy with topical anesthesia. AB - To evaluate the safety of topical lidocaine anesthesia in children undergoing bronchoscopy, we determined SLC in 15 children aged 3 months to 9.5 years during flexible fiberoptic bronchoscopy. A total lidocaine dose of 3.2 to 8.5 (mean +/- SEM = 5.7 +/- 0.5) mg/kg was administered to nose, larynx and bronchial tree over 9 to 45 (mean +/- SEM = 20 +/- 2.7) minutes. No complication occurred during the procedure. Peak SLC were 1-3.5 (mean +/- SEM = 2.5 +/- 0.2) micrograms/ml. The Vd beta was 1.79 +/- 0.19 L/kg, the t1/2 beta was 109 +/- 12 minutes, and the total body clearance 12.2 +/- 1.1 ml/min/kg. Peak SLC correlated well with the dose expressed as mg/kg (r = 0.59, p less than 0.025), and even better when related to body surface area (r = 0.63, p less than 0.01). Lidocaine doses up to 8.5 mg/kg proved safe and resulted in therapeutic SLC in our patients. Lidocaine dose up to 7 mg/kg appears to be safe provided that it does not exceed an upper limit of 175 mg/m2 and is gradually administered over a minimum of 15 minutes. Doses of 7-8.5 mg/kg appear to be safe when administered over longer periods. PMID- 2245678 TI - Optimal interpretation of the supine exercise electrocardiogram in patients with right bundle branch block. AB - A detailed analysis of the exercise ECG was performed in 82 patients with right bundle branch block who underwent supine exercise equilibrium radionuclide angiography. The sensitivity and specificity of each individual electrocardiographic lead for the detection of a positive radionuclide angiogram was determined. Leads V5 and V6 had a sensitivity of 58 percent and a specificity of 89 percent. The limb leads and lead V4 had a lower sensitivity, but an equivalent specificity. Leads V1 and V3 each had a clearly lower specificity that ranged from 56 to 67 percent. Receiver operating characteristic curve analysis demonstrated that the optimal interpretation of the exercise ECG included the limb leads and V4 to V6, but not V1 to V3. The results of coronary angiography in the subset of 16 patients who underwent this procedure confirmed these findings. PMID- 2245679 TI - Reduction in bleeding after heart-lung transplantation. The importance of posterior mediastinal hemostasis. AB - To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results. PMID- 2245680 TI - Clinical antecedents to in-hospital cardiopulmonary arrest. AB - While the outcome of in-hospital cardiopulmonary arrest has been studied extensively, the clinical antecedents of arrest are less well defined. We studied a group of consecutive general hospital ward patients developing cardiopulmonary arrest. Prospectively determined definitions of underlying pathophysiology, severity of underlying disease, patient complaints, and clinical observations were used to determine common clinical features. Sixty-four patients arrested 161 +/- 26 hours following hospital admission. Pathophysiologic alterations preceding arrest were classified as respiratory in 24 patients (38 percent), metabolic in 7 (11 percent), cardiac in 6 (9 percent), neurologic in 4 (6 percent), multiple in 17 (27 percent), and unclassified in 6 (9 percent). Patients with multiple disturbances had mainly respiratory (39 percent) and metabolic (44 percent) disorders. Fifty-four patients (84 percent) had documented observations of clinical deterioration or new complaints within eight hours of arrest. Seventy percent of all patients had either deterioration of respiratory or mental function observed during this time. Routine laboratory tests obtained before arrest showed no consistent abnormalities, but vital signs showed a mean respiratory rate of 29 +/- 1 breaths per minute. The prognoses of patients' underlying diseases were classified as ultimately fatal in 26 (41 percent), nonfatal in 23 (36 percent), and rapidly fatal in 15 (23 percent). Five patients (8 percent) survived to hospital discharge. Patients developing arrest on the general hospital ward services have predominantly respiratory and metabolic derangements immediately preceding their arrests. Their underlying diseases are generally not rapidly fatal. Arrest is frequently preceded by a clinical deterioration involving either respiratory or mental function. These features and the high mortality associated with arrest suggest that efforts to predict and prevent arrest might prove beneficial. PMID- 2245681 TI - Rapid diagnosis of lung cancer from palpable metastases by needle thrust. AB - This study encourages the use of percutaneous FNB to diagnose and stage advanced lung cancer in patients with palpable metastases in supraclavicular lymph nodes or soft tissues. Percutaneous FNB of metastases is much easier to learn than transthoracic needle aspiration: the superficial target is anchored and sampled with multiple passes using a short needle grasped directly in the fingers. It is fast, accurate, economical and nearly free of risk and pain. The technique saves time and money because it is the only procedure needed by many patients with palpable disease in stage IIIB and IV. Bronchoscopy, transthoracic needle aspiration and open surgical biopsy thus can be avoided in most patients with palpable metastases. Prompt diagnosis by FNB of metastases speeds palliation for patients with urgent need. Tumor cell type from FNB correlated with cytologic findings from sputum samples, bronchoscopy specimens and autopsy results. PMID- 2245682 TI - Clinical dysautonomia in patients with bronchial asthma. Study with seven autonomic function tests. AB - Fifty asthmatic patients and 20 healthy control subjects, carefully age- and sex matched, were subjected to seven standardized tests to evaluate their autonomic status. Due care was taken to remove factors which could interfere with results. Of the tests concerned with the parasympathetic system, the intravenous atropine test (p greater than 0.10) and heart rate response to standing (p greater than 0.01) which measured the basal parasympathetic tone, did not show a significant difference. Tests requiring stimulation of the parasympathetic system, ie, deep breathing test (p less than 0.001), Valsalva maneuver (p less than 0.001), and carotid sinus massage (p less than 0.001) showed significantly heightened response. Postural fall of blood pressure (p greater than 0.10) and sustained hand grip test (p greater than 0.10), chiefly concerned with the sympathetic system, did not show a significant difference. Of the 50 asthmatic patients, nine were atopic and 41 nonatopic. When the results were compared in the two groups separately, we found that there was no alteration in the measurements except the intravenous atropine test which showed heightened response with atopic subjects (p less than 0.05). These results suggest that hyperresponsiveness of the parasympathetic system is an important factor in producing bronchial spasm in asthmatic patients, and atopic and nonatopic subjects do not differ much in their autonomic status. PMID- 2245683 TI - Maxillofacial surgery and nasal CPAP. A comparison of treatment for obstructive sleep apnea syndrome. AB - Nasal continuous positive airway pressure (CPAP) is the primary therapy for obstructive sleep apnea syndrome (OSAS). Recent reports have indicated, however, that there is a small but significant number of failures related to patient compliance. Primary surgical treatment, which has been uvulopalatopharyngoplasty (UPPP), has declined because of poor results. A reviewed of UPPP failures has shown that while UPPP eliminated palatal obstruction, it failed to eliminate base of tongue obstruction. Maxillofacial surgery has been reported as treatment of OSAS by correcting base of tongue obstruction. Thirty patients with severe OSAS were evaluated to compare nasal CPAP and maxillofacial surgery. The goal was to determine if our surgical protocol was as effective as nasal CPAP. All patients initially underwent baseline diagnostic polysomnography to document OSAS. A nasal CPAP study was performed to determine the appropriate positive end-expiratory pressure. The patients in this study were using nasal CPAP, but they found it unacceptable as long-term treatment and elected surgery. Maxillofacial surgery consisted of maxillary, mandibular, and hyoid advancement. Polysomnography was performed six months following surgery and compared with the night 2 CPAP results. The parameters included in the investigation were the respiratory disturbance index (RDI), lowest SaO2, number of SaO2 falls below 90 percent, total sleep time (TST), REM sleep percent, stage 3-4 sleep percent, and wake after sleep onset. The mean RDI before treatment was 72.0 (SD 25.7). After completing therapy, the RDI from surgery and CPAP was 8.8 (SD 6.0) and 8.6 (SD 4.1), respectively. The mean low SaO2 prior to treatment was 61.0 (SD 13.5), and the CPAP results and postsurgical results were 86.2 (SD 5.5) and 86.1 (SD 4.2), respectively. An analysis of variance was used to examine the results, and there was no statistical difference between nasal CPAP and surgery for all respiratory variables. PMID- 2245684 TI - Effect of inhaled methacholine on inspiratory flow. AB - One hundred consecutive outpatients with symptoms suggestive of asthma who came to the Pulmonary Function Laboratory for a methacholine challenge test were studied. In addition to the forced expiratory maneuvers, forced inspiratory maneuvers were performed before and after the maximal response to methacholine. In 24 patients, the methacholine challenge suggested that they had asthma (forced expiratory volume in 1 s [FEV1] decrease greater than or equal to 20 percent). Six of these 24 patients also had a decrease in maximal forced inspiratory flow (FIFmax) greater than or equal to 20 percent and nine had a decrease in forced inspiratory flow at 50 percent of vital capacity (FIF50) greater than or equal to 20 percent, suggesting that bronchoconstriction can cause decreased inspiratory as well as expiratory flows. In 76 patients, the methacholine challenges were "negative" (FEV1 decrease less than or equal to 20 percent), suggesting that they did not have asthma. Nevertheless, in 11 of these 76 patients the FIFmax decrease was greater than or equal to 20 percent, and in 14 patients the FIF50 decrease was greater than or equal to 20 percent, suggesting that intermittent central airway obstruction is responsible for these patients' symptoms. PMID- 2245685 TI - Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension. AB - After pulmonary thromboendarterectomy, performed for relief of chronic thromboembolic pulmonary hypertension, perfusion lung scans have frequently disclosed new perfusion defects in segments served by undissected pulmonary arteries. Our hypotheses were that these new postoperative defects occurred with great frequency and did not represent postoperative vessel occlusion. We retrospectively reviewed the preoperative and postoperative perfusion scans of 33 consecutive patients undergoing pulmonary thromboendarterectomy. New postoperative perfusion defects were noted in 23 of 33 patients. The incidence of new defects was increased tenfold in segments that had (1) normal preoperative angiographic findings, (2) normal preoperative radionuclide perfusion, and (3) not been entered at the time of surgery. Postoperative angiograms, available in 15 of 33 patients, documented the nonembolic, nonocclusive nature of the new perfusion scan defects. The most plausible alternate explanation for this previously undescribed finding is a redistribution of pulmonary arterial resistance induced by the thromboendarterectomy, namely, a pulmonary vascular "steal." PMID- 2245686 TI - Normal spirometric values in healthy Hispanic Americans. AB - FVC, FEV1, FEV1/FVC, and FEF25-75% were measured in 259 (116 men and 143 women) healthy nonsmoking Hispanic American volunteers from Utah and California. Linear regression equations were created for women greater than or equal to age 20 years and men greater than or equal to age 25 years using height, age, and weight as independent variables and the spirometric indices as dependent variables. Weight was a significant predictor only for female FEV1. The raw data from this study were compared with data from our previous studies in North American Indians and Salt Lake City whites with Middle European ethnic backgrounds. No differences were found for any of the age and height coefficients. The only differences found were in the comparisons of the equation intercepts (bias) for male FVC and FEV1 between data for the Salt Lake City white subjects and both Hispanic American and North American Indian men. These small biases could be explained by technical or sampling biases or they may represent small ethnic differences. Although the differences from our Salt Lake City study are small, we recommend that ethnic specific equations be used where they are available. PMID- 2245687 TI - The effect of multiple-dose oral lomefloxacin on theophylline metabolism in man. AB - Single-dose plasma pharmacokinetics of theophylline (6 mg/kg intravenously) and renal excretion of theophylline and its metabolites, resulting from 8-oxidation and N-demethylation, were investigated in eight healthy volunteers before and at day 3 of concomitant oral administration of the quinolone derivative lomefloxacin (400 mg twice daily). Plasma samples were collected until 24.5 h, and urine samples were collected until 72 h after theophylline administration. The concentrations of theophylline and the major metabolites, resulting from N demethylation and 8-oxidation, were measured utilizing a high-pressure liquid chromatography (HPLC) technique. No significant changes in theophylline half life, volume of distribution, protein binding, total body clearance, or renal clearance were noted. In addition, renal excretion of unchanged theophylline, the products of the N-demethylation, 3-methylxanthine, and 1-methyluric acid, and the product of the 8-oxidation, 1,3-dimethyluric acid, were not altered by simultaneous administration of lomefloxacin. Orally administered lomefloxacin is absorbed quickly and to a high extent. During administration of 400 mg twice daily, plasma concentrations reached are well above minimum inhibitory concentration (MIC) values of pathogens that are frequently isolated in lower respiratory tract infections. This study shows that lomefloxacin in a twice daily dose of 400 mg does not effect theophylline metabolism. Lomefloxacin and theophylline can be coadministered without concern about effects of lomefloxacin on theophylline pharmacokinetics. PMID- 2245688 TI - Measurements of right ventricular volumes during fluid challenge. AB - The effects of fluid loading on RV function were studied in 41 acutely ill patients monitored with a modified pulmonary artery catheter equipped for measuring RVef. Hemodynamic evaluation was performed before and after infusion of 300 ml of 4.5 percent albumin solution in 30 min. Changes in SI did not correlate with Pra or Ppao but did with RVEDVI. For the entire group, RVef was unchanged (27 +/- 9 vs 27 +/- 9 percent). In the eight patients with an initial RVEDVI greater than 140 ml/m2, the fluid challenge increased Pra and Ppao and reduced LVSWI without any other significant effect. There was no significant correlation between RVEDVI and Pra and only a weak correlation between RVESVI and Ppa. However, there was a highly linear correlation between both RVEDVI and RVESVI and changes in RVEDVI and in RVESVI, suggesting that in the absence of severe pulmonary hypertension RV output is primarily dependent on RV preload. PMID- 2245689 TI - Pathologic dependence of oxygen consumption on oxygen delivery in acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia. AB - Oxygen consumption is pathologically dependent on oxygen delivery in ARDS and sepsis. We asked whether oxygen consumption is dependent on oxygen delivery in severe acute respiratory failure secondary to AIDS-related PCP. In five patients who had AIDS-related PCP, diffuse bilateral pulmonary infiltrates, no evidence of bacterial infection, and acute respiratory failure requiring mechanical ventilation with arterial oxygen tensions less than 75 mm Hg while breathing at least 50 percent oxygen, and PEEP greater than 10 cm H2O, we determined oxygen delivery and consumption by calculation from thermodilution cardiac output and arterial and mixed venous oxygen contents. Oxygen delivery was increased using transfusion of two units of packed red blood cells over one hour. Oxygen delivery increased 22 percent (638 +/- 204 to 778 +/- 201 ml/min.m2, p less than or equal to 0.006). Oxygen consumption increased 11 percent (134 +/- 34 to 149 +/- 29 ml/min.m2, p less than or equal to 0.02). The oxygen extraction ratio did not change. We conclude that similar to ARDS and sepsis, oxygen consumption may be pathologically dependent on oxygen delivery in patients who have severe acute respiratory failure secondary to AIDS-related PCP. PMID- 2245690 TI - Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. AB - Inadequate tissue oxygenation may occur in critically ill patients with sepsis despite an apparently adequate O2 transport (QO2), and this may contribute to the development of an O2 debt and also to multiple organ failure. It has been shown that increasing QO2 by infusing a vasodilator may reveal this O2 debt in septic patients. To investigate whether the site of action of vasodilators may be of importance in unmasking such an O2 debt, we administered prostacyclin, a prostaglandin with a preferential effect on the microcirculation, and phentolamine, an arteriolar vasodilator, in 11 patients studied during the first 48 hours after the onset of sepsis, and compared their effect on whole body oxygen consumption (VO2) and skin microvascular blood flow. The results demonstrated that increasing QO2 by prostacyclin but not by phentolamine significantly increases VO2 in critically ill patients with sepsis. The site of action of vasodilators may therefore play an important role in their ability to unmask an O2 debt. PMID- 2245691 TI - Pseudomonas aeruginosa compared with Escherichia coli produces less endotoxemia but more cardiovascular dysfunction and mortality in a canine model of septic shock. AB - We investigated the effects of two different Gram-negative bacteria and radiation induced leukopenia on endotoxemia, cardiovascular abnormalities, and mortality in a canine model of septic shock. Serial hemodynamics were measured in conscious dogs using radionuclide heart scans and thermodilution cardiac output catheters. Plasma endotoxin concentrations were determined with a chromogenic Limulus amebocyte lysate assay. Viable Pseudomonas aeruginosa or Escherichia coli implanted intraperitoneally produced concordant hemodynamic patterns of septic shock (p less than 0.01). Endotoxin concentrations were more than tenfold lower in dogs infected with P aeruginosa compared with E coli (p less than 0.0001). Despite lower endotoxin levels, P aeruginosa-infected dogs had a higher mortality (p less than 0.01), more severe hypotension (p less than 0.05), and greater depression of the left ventricular ejection fraction (p less than 0.05) than dogs with E coli sepsis. A nonlethal E coli challenge combined with leukopenia (induced by a nonlethal dose of radiation) resulted in a mortality of 60 percent (p less than 0.01) without greater cardiovascular dysfunction or higher endotoxin concentrations. These findings suggest that bacterial products other than endotoxin and host-related factors may be important contributors to the toxicity, cardiovascular instability, and mortality of Gram-negative septic shock. Quantitative determinations of plasma endotoxin are unlikely to correlate with the clinical severity of septicemia in heterogeneous patient populations infected with different Gram-negative organisms. PMID- 2245692 TI - Selection and evaluation of recipients for heart-lung and lung transplantation. AB - Heart-lung and lung transplantation is being successfully performed with increasing frequency in patients with end-stage cardiopulmonary and pulmonary disease. Transplantation must now be considered as a therapeutic option in selected patients, and physicians are required to understand the principles involved for determining suitable candidates and operative procedures of choice. Indications, contraindications, and choice of operation with respect to underlying disease are discussed herein, as are methods of evaluation and appropriate timing for transplantation. Special considerations regarding specific patient populations are also addressed. In properly selected patients, heart-lung and lung transplantation provide a viable therapeutic option in those with end stage disease who are unresponsive to conventional management. PMID- 2245693 TI - Roentgenogram of the month. A patient referred for steroid-resistant asthma. PMID- 2245694 TI - Role of nocturnal oxygen therapy in obstructive sleep apnea. When should it be used? PMID- 2245695 TI - Tuberculous mastitis. PMID- 2245696 TI - Acute myocardial infarction resulting from the migration of a Greenfield filter. AB - A paraplegic patient who underwent the placement of Greenfield filters to prevent pulmonary emboli had one of the filters migrate proximally to the junction of the inferior vena cava and right atrium, then into the right atrium a few months later. This resulted in an acute myocardial infarction by apparently causing an intimal dissection of the posterior descending artery. Treatment, follow-up and causes of filter migration are discussed. PMID- 2245697 TI - Bronchogenic carcinoma in situ on the carina eradicated by endobronchial biopsy. AB - Squamous cell carcinoma in situ of the bronchus is a rare disorder in an isolated clinical setting. We present a case of carcinoma in situ located on the carina with excisional biopsy via a fiberoptic bronchoscope and no recurrence after five years. To our knowledge, this represents the only case of carcinoma in situ treated solely with excisional biopsy. This case further emphasizes the importance of securing biopsy specimens for all mucosal abnormalities and raises the possibility of limited excision as sole therapy for carcinoma in situ. PMID- 2245698 TI - Rapid oral desensitization to isoniazid and rifampin. AB - A 45-year-old black woman, sputum positive for acid-fast bacilli, developed hypersensitivity to both isoniazid and rifampin. She was admitted to the hospital and desensitized to both medications using modified penicillin protocols. Skin testing was negative to both drugs. Desensitization to isoniazid was complicated by a drug fever that was controlled by prednisone. The patient was able to maintain once-a-day dosing without incident even with steroid taper. To our knowledge, this is the first reported case of dual isoniazid and rifampin hypersensitivity with rapid oral desensitization. PMID- 2245699 TI - Tracheal stenosis and failure to wean from mechanical ventilation due to herpetic tracheitis. AB - A 64-year-old man with chronic obstructive pulmonary disease presented with pneumococcal pneumonia that progressed to respiratory failure within one week, requiring mechanical ventilation. Despite a low minute ventilation and clear chest roentgenogram, multiple weaning attempts failed. Bronchoscopy revealed significant narrowing of the distal trachea with erythema, edema, and ulceration of the mucosa. Cytology of tracheal washings was consistent with herpes simplex virus, and the patient was successfully extubated following treatment with intravenous acyclovir. Bronchoscopy following acyclovir therapy demonstrated resolution of the inflammation and narrowing. Herpetic tracheitis is a rarely recognized reversible cause of tracheal stenosis, especially in a nonimmunocompromised patient. It should be suspected in patients without an obvious cause of failure to wean from mechanical ventilation, and can be successfully treated with acyclovir. PMID- 2245700 TI - Osler-Weber-Rendu disease and pulmonary arteriovenous fistulas. Deterioration and embolotherapy during pregnancy. AB - Several reports have implicated pregnancy as a cause of deterioration in patients with pulmonary arteriovenous fistulas. We report a 27-year-old woman with multiple pulmonary arteriovenous fistulas who required coil spring embolotherapy in her 24th week of pregnancy due to a spontaneous hemothorax and hypoxemia. PMID- 2245701 TI - Septic pulmonary embolism complicating a central venous catheter. AB - Bacteremia is a recognized complication in patients with indwelling central venous catheters. More recently pulmonary embolism in such patients has also been described. Despite abundant clinical experience with these devices, to our knowledge, septic pulmonary embolism has not been reported in adult patients. This case illustrates such a complication. PMID- 2245702 TI - Adult respiratory distress syndrome due to blastomycosis during pregnancy. AB - A 23-year-old healthy woman in her third trimester of pregnancy developed adult respiratory distress syndrome secondary to Blastomyces dermatitides. Pregnancy related immunosuppression was believed to be responsible for the fungal infection. Following emergency delivery of the infant and a full course of amphotericin B therapy, the patient made an uneventful recovery. Although the fetal and maternal sides of the placenta demonstrated fungal spores, the child remained healthy. To our knowledge, this is the first report of blastomycosis associated adult respiratory distress syndrome occurring during pregnancy. PMID- 2245703 TI - Phrenomediastinal echinococcosis. AB - A patient with the rare presentation of posterior mediastinal echinococcosis is reported. Magnetic resonance imaging (MR) demonstrated the extension of a primary retroperitoneal cyst into the posterior mediastinum which was subsequently confirmed surgically to be of echinococcal origin. Such a case of phrenomediastinal echinococcosis has been described only once before in literature. PMID- 2245704 TI - Pneumomediastinum, pneumothorax and subcutaneous emphysema following the measurement of maximal expiratory pressure in a normal subject. AB - Mediastinal and subcutaneous emphysema have been reported as a consequence of deliberate manipulations of the breathing pattern producing a Valsalva-like maneuver in healthy subjects. We present a case of pneumomediastinum, pneumothorax and subcutaneous emphysema occurring in a normal volunteer after repeated measurements of the PEmax. PMID- 2245705 TI - Management of Brucella endocarditis with aortic root abscess. AB - Three cases of Brucella endocarditis with aortic root abscess are reported. Two patients were successfully managed by a combination of medical therapy and surgery. The third patient died suddenly 36 hours after admission to hospital. PMID- 2245706 TI - Ear involvement in the yellow nail syndrome. AB - Recognized features of the yellow nail syndrome include yellow nails, lymphedema, and pleural effusions. We report a patient with the additional feature of keratosis obturans, which may be a manifestation of this syndrome in the external ear. PMID- 2245707 TI - Bilious pleural effusion following liver biopsy. AB - Pleural effusions in patients with chronic liver disease are common and usually are of little consequence. Bilious pleural effusion can occur following percutaneous biopsy or cholangiography procedures if the pleura is traversed. This report emphasizes the role of biliary tract obstruction in the development of a bilious effusion and the importance of biliary tract decompression in treatment. We discuss the laboratory evidence supporting the diagnosis of bilious effusion and review the reported experience with this complication. PMID- 2245708 TI - Permanent venous access via subcutaneous infusion port in severe asthma. AB - A subcutaneous infusion port was implanted in a 34-year-old patient with frequent and severe asthma attacks to ensure prompt and reliable venous access. Difficulties with peripheral venous access were possible cofactors necessitating mechanical ventilation on two occasions before this implantation. The method described is simple and seems useful for asthmatics in need of frequent parenteral medication. PMID- 2245709 TI - Bronchoscopy in hemoptysis. PMID- 2245710 TI - Arterial oxygenation in carbon monoxide poisoning. PMID- 2245711 TI - Needle aspiration in lung cancer. PMID- 2245712 TI - L-tryptophan induced cough and pleural effusions associated with the eosinophilia myalgia syndrome. PMID- 2245713 TI - Spontaneous resolution of endobronchial Mycobacterium avium-intracellulare infection in a patient with AIDS. PMID- 2245714 TI - Wandering pacemaker. PMID- 2245715 TI - Nasal CPAP for severe hypoxia. PMID- 2245716 TI - Caring for mechanically ventilated patients at home. PMID- 2245717 TI - Ophthalmologic complications in primary pulmonary hypertension. PMID- 2245718 TI - Pleural involvement in hairy cell leukemia response to recombinant interferon alpha. PMID- 2245719 TI - Left pulmonary artery thrombosis in chlorpromazine-induced lupus. PMID- 2245720 TI - Digital clubbing in hashish addicts. PMID- 2245721 TI - Primary non-Hodgkin's lymphoma of the larynx treated only by chemotherapy. PMID- 2245722 TI - Regression of primary pulmonary hypertension. PMID- 2245723 TI - HIV infection in not-at-risk tuberculous patients in Spain. PMID- 2245724 TI - Spontaneous hemorrhage of an ectopic mediastinal thyroid. PMID- 2245725 TI - Peer status and aggression in boys' groups: developmental and contextual analyses. AB - The social transactions of popular, rejected, neglected, and average first- and third-grade boys were examined during their initial encounters with peers. 23 groups of 5 or 6 boys each were observed for 45-min free-play sessions conducted on 5 consecutive days, with sociometric interviews following each session. Social preference in the play groups correlated significantly with classroom social preference after the third and subsequent play sessions for the third graders, and after the fourth and subsequent sessions for the first graders. The observational coding system distinguished 4 types of aggressive behavior that were hypothesized to relate to peer status in different ways. The first, rough play, was not related to peer status. However, rejected boys at both ages displayed significantly higher rates of angry reactive aggression and instrumental aggression than average boys. The relation between bullying and peer status varied with the age of the child. Popular first graders engaged in more bullying than average first graders, but popular third graders did not differ from average in bullying. Other questions concerned the temporal relation between play group behaviors and social preference scores within the group. Socially interactive behaviors anteceded high preference by peers, and low preference in turn led to social isolation in subsequent sessions. PMID- 2245726 TI - Peers' perceptions of the consequences that victimized children provide aggressors. AB - Fourth- through seventh-grade children (mean age 11.5 years) estimated the likelihood that various consequences would occur following hypothetical acts of aggression toward victimized and nonvictimized classmates. Children also indicated how much they would care if the consequences were to occur. When contemplating aggression toward victimized classmates, children were more likely to expect tangible rewards, more likely to expect signs of victim suffering, and less likely to expect retaliation than when considering aggression against nonvictimized classmates. Also, when considering aggression toward victimized classmates, children cared more about securing tangible rewards but were less disturbed by the thought of hurting their victims or by the thought of their victims retaliating than when imagining aggression toward nonvictimized classmates. The foregoing pattern was stronger for boys than for girls. Implications for theories of aggression and for intervention with aggressive and victimized children are discussed. PMID- 2245727 TI - Age differences in children's memory of information about aggressive, socially withdrawn, and prosociable boys and girls. AB - Age differences in children's memory for information about aggression, prosociability, and social withdrawal were examined in 2 studies, one using a recall task, the other a recognition task. In both studies, second- and sixth grade subjects heard descriptions of hypothetical boys and girls described as (a) aggressive, (b) socially withdrawn, or (c) prosociable, and their memory of the items in the descriptions was assessed. With the recall task, age-related increases were observed for the descriptions of the girl peers and for the withdrawn boy peer. With the recognition task, age differences were observed in memory for information about social withdrawal and prosociability but not aggression, and memory for information about aggression was better for the boy peer than girl peer, whereas the opposite pattern was observed for information about withdrawal. These results indicate that school-age and early adolescent children's recall of information about a peer is affected by the peer's gender. PMID- 2245728 TI - Children's perceptions of self and of relationships with others as a function of sociometric status. AB - We studied the relations among children's reports about their own competence, objective measures of their competence, and their views of important relationships with others as a function of sociometric status. 515 third- and fourth-grade children responded to questions about aspects of their personal competence and about their relationships with mothers, fathers, teachers, and best friends. Rejected children reported the least supportive relationships overall with their fathers of any status group; this was especially true of rejected-aggressive children. Neglected children reported the lowest perceived social competence with peers. The subjective reports of rejected but not neglected children overestimated their social competence as rated by peers. Relative to teacher reports, rejected-aggressive children also overestimated their behavioral competence. While highlighting heterogeneity among low-accepted groups, these results add to knowledge about the subjective experiences of children who are unpopular with peers. PMID- 2245729 TI - Preadolescent peer status, aggression, and school adjustment as predictors of externalizing problems in adolescence. AB - The comparative effectiveness of preadolescent aggressive behavior, peer rejection, and school functioning were evaluated in the prediction of adolescent delinquency and school maladjustment. Fifth-grade children (n = 112, 69% white, 53% male, M = 11 years old) were followed forward for 7 years until the end of high school. Rejected children were more likely to have a nonspecific negative outcome and more types of negative outcomes than average, popular, or neglected children, particularly among the white students. However, in regression models containing sex, race, aggression, frequent school absences, low grades, and rejection, the only significant predictor of juvenile delinquency or of a nonspecific negative outcome was aggression toward peers. Both aggression and frequent school absences were significant predictors of early school withdrawal. Analyses for the white children in the sample revealed that both rejection and aggression best predicted to the nonspecific negative outcome, whereas aggression alone best predicted to school dropout and to having one or more police contacts. Implications for future longitudinal outcome research and for risk-group identification in racially heterogeneous samples are discussed. PMID- 2245730 TI - The fate of early experience following developmental change: longitudinal approaches to individual adaptation in childhood. AB - 2 strategies were used to investigate the continued impact of early experience and adaptation given subsequent experience and/or developmental change in a poverty sample (N = 190). Groups were defined whose adaptation was similar during the preschool years but consistently different earlier; then these 2 groups were compared in elementary school. In addition, a series of regression analyses was performed in which variance accounted for by near-in or contemporary predictors of adaptation in middle childhood was removed before adding earlier adaptation in subsequent steps. Children showing positive adaptation in the infant/toddler period showed greater rebound in the elementary school years, despite poor functioning in the preschool period. Regression analyses revealed some incremental power of early predictors with intermediate predictors removed. The results were interpreted as supporting Bowlby's thesis that adaptation is always a product of both developmental history and current circumstances. While this research cannot resolve such a complicated issue, it does point to the need for complex formulations to guide research on individual development. PMID- 2245731 TI - Preadolescents' social-emotional adjustment and selective attrition in family research. AB - Researchers often ask subjects to commit considerable time and effort to completing tasks that are not especially enjoyable. In a multistage investigation of sixth-grade boys and their families, we hypothesized that boys who were prone to high levels of distress (i.e., anxiety, depression, low self-esteem, and low well-being) but only low or moderate levels of self-restraint (i.e., consideration of others, impulse control, suppression of aggression, and responsibility) would be particularly unlikely to agree to participate. Consistent with this hypothesis, boys from 33 classrooms who were nominated by their peers as high in distress and moderate or low in self-restraint were significantly less likely than other boys to take part in an in-class survey. In addition, the families of boys who scored high in distress and moderate or low in self-restraint on the Weinberger Adjustment Inventory (WAI) were less likely than other families to agree to an observation session in their homes and to a series of telephone interviews about daily events in the boys' lives. Across the 3 phases of the research, the cumulative attrition rate of these at-risk boys was approximately 80%, compared to only 50% for those low in distress and/or high in self-restraint. These results suggest that the children of greatest interest in studies of social competence and family interaction may often be among those least adequately represented. PMID- 2245732 TI - Perceptions of sibling relationships during middle childhood and adolescence. AB - Children in grades 3, 6, 9, and 12 were administered the Sibling Relationship Questionnaire. Relationships were rated as progressively more egalitarian across the 4 grade groups, with adolescents reporting less dominance and nurturance by their older siblings than younger participants. Adolescents also reported less companionship, intimacy, and affection with siblings than younger participants reported. Levels of perceived conflict with younger siblings were moderately high across all 4 grades, whereas ratings of conflict with older siblings were progressively lower across the 4 grades. The findings suggested that sibling relationships: (a) become more egalitarian and less asymmetrical with age, (b) become less intense with age, and (c) encompass experiences that are partially determined by the child's standing in the family constellation. PMID- 2245733 TI - Children's representations of the pattern of daily activities. AB - An important part of humans' knowledge of time depends on forming mental representations of recurrent temporal patterns. This study was an attempt to characterize the representations of one such pattern--the relative times of occurrence of daily activities such as waking, lunch, dinner, and going to bed in 4-9-year-old children. The results of 3 experiments showed that by 5 years of age children can judge the backward order of daily activities, judge the forward order from multiple reference points within the day, and evaluate the lengths of intervals separating daily activities. By about 7 years, children can also judge backward order from multiple reference points. These findings impose constraints on the types of representational models that can explain young children's knowledge of this pattern. The results also show that certain operations can be performed on this content about 6 years earlier than on 2 other temporal contents -the patterns of days of the week and months. PMID- 2245734 TI - Children's housework and psychosocial functioning: the mediating effects of parents' sex-role behaviors and attitudes. AB - We examined sex-typed housework of children from dual- and single-earner families and its implications for children's adjustment as a function of congruencies between children's work and parents' sex-role behaviors and attitudes. Participants were 152 firstborn 9-12-year-olds (85 girls, 67 boys) and their parents. All fathers and 50% of mothers were employed. In home interviews parents rated their sex-role attitudes, and children rated their competence, stress, and parent-child relationships. In 7 nightly telephone interviews, children and parents described their household tasks for that day. Analyses revealed sex and earner-status differences in children's and parents' involvement in traditionally feminine and masculine tasks. Correlations between levels of parents' and children's task involvement were significant only in the case of fathers and sons in single-earner families. Regarding the connections between task performance and child adjustment, we found that incongruency between boys' sex-typed tasks and their fathers' sex-role behaviors and attitudes was linked to poorer psychosocial functioning, a pattern that did not hold for girls. PMID- 2245735 TI - The relation of gender understanding to children's sex-typed preferences and gender stereotypes. AB - Our goal was to explore how children's understanding of gender as a social category relates to their acquisition of sex-typed knowledge and preferences. Children's gender concepts, sex-typed preferences, and stereotyped knowledge were measured in 61 boys and girls (3-5 years). Gender concept measures included ability to identify and to discriminate the sexes, understanding gender group membership, temporal stability of gender, and gender consistency over situational changes. Children improved with age on most of the measures except gender consistency. With the exception of consistency, measures of gender concept understanding were found to be related to children's stereotyped toy and clothing knowledge and/or to their sex-typed toy preferences (with age controlled). It was shown that only rudimentary gender understanding is needed prior to children learning about sex stereotypes and prior to showing strong sex-typed preferences for peers or toys. The roles of gender identity, stability, consistency, and group membership in the sex-typing process are discussed. PMID- 2245736 TI - The role of attitudes and interventions in gender-schematic processing. AB - Research on gender-schematic processing has shown that children often forget and/or distort counterstereotypic information. This process may in part explain the limited impact of past intervention efforts in which children were simply exposed to counterstereotypic information. Here we attempt to reduce schematic processing distortions by first teaching children decision rules about occupational sorting based not on gender but rather on interests and skills. It was hypothesized that this intervention would lead to greater flexibility in children's beliefs about what men and women can do. Assuming this effect was found, the study was designed to provide an experimental test of the hypothesized relation between attitudes and memory that had been demonstrated only correlationally in previous research. As predicted, the experimental intervention with elementary school children led to a reduction of occupational stereotyping. Children's own occupational aspirations were not, however, significantly affected. Consistent with the hypothesized effect of attitudes on memory, children in the experimental intervention showed superior recall of counterstereotypic information in a later memory test. Results are discussed with respect to the utility of cognitive-developmental theory for planning and evaluating future interventions. PMID- 2245737 TI - Children's sex-related stereotyping of colors. AB - 4 studies addressed children's sex-related stereotyping of colors. Study 1 examined preschoolers' awareness of color stereotypes. Children were presented with 6 toy animals, identical except for color, and were asked to identify the sex of each animal and to select a favorite. Both sex identifications and toy preferences were highly consistent with adult color stereotypes. Study 2 demonstrated that clothing color influences preschool, kindergarten, and first grade children's impressions of other children whose sex is known. Studies 3 and 4 indicated that the effects of stereotyping based on color are modest in comparison to the effects of stereotyping based directly on sex. In addition, color stereotyping did not show the regular age-related increase that is characteristic of sex-role stereotyping. PMID- 2245738 TI - Nouns mark category relations: toddlers' and preschoolers' word-learning biases. AB - Recent research suggests that preschool children approach the task of word learning equipped with implicit biases that lead them to prefer some possible meanings over others. The noun-category bias proposes that children favor category relations when interpreting the meaning of novel nouns. In the series of experiments reported here, we develop a stringent test of the noun-category bias and reveal that it is present in children as young as 2 years of age. In each experiment, children participated in a 5-item match-to-sample task. Children were presented with a target item (e.g., a cow) and 4 choices, 2 of which belonged to the same superordinate category as the target (e.g., a fox and a zebra) and 2 of which were thematically related to the target (e.g., milk and a barn). In Experiment 1 we demonstrate that novel nouns prompt preschool children to attend to superordinate-level category relations, even in the presence of multiple thematic alternatives. In Experiment 2, we ascertain that the bias is specific to nouns; novel adjectives do not highlight superordinate category relations. In Experiment 3, we demonstrate the noun-category bias in 2-year-olds. The nature and utility of the noun-category bias are discussed. PMID- 2245739 TI - The principle of mutual exclusivity in word learning: to honor or not to honor? AB - According to Markman and Wachtel, children assume that nouns pick out mutually exclusive object categories, and so each object should have only one category label. While this assumption can be useful in word learning, it is not entirely reliable. Therefore, children need to learn when to and when not to make this assumption. 6 studies examined whether knowledge about hierarchical organization of categories and about cross-language equivalents for object labels can help children limit their use of this assumption appropriately. These studies revealed that adults as well as children resisted assigning 2 novel names to the same object in some situations. By age 4, children also seemed to know enough about categorization to accept 2 names for an object if the names picked out categories from different levels of a hierarchy (e.g., animal and lemur) but not if they picked out categories from the same level (e.g., lemur and seal). Moreover, monolingual as well as bilingual children seemed to know enough about languages to accept 2 names for the same object if the names clearly came from different languages. Together, these findings suggest that even preschool children can make use of knowledge about language and categorization to fine tune the mutual exclusivity assumption in order to use it effectively in word learning. PMID- 2245740 TI - Heuristics of reasoning and analogy in children's visual perspective taking. AB - We propose that children's reasoning about others' visual perspectives is guided by simple heuristics based on a perceiver's line of sight and salient features of the object met by that line. In 3 experiments employing a 2-perceiver analogy task, children aged 3-6 were generally better able to reproduce a perceiver's perspective if a visual cue in the perceiver's line of sight sufficed to distinguish it from alternatives. Children had greater difficulty when the task hinged on attending to configural cues. Availability of distinctive cues affixed on the objects' sides facilitated solution of the symmetrical orientations. These and several other related findings reported in the literature are traced to children's reliance on heuristics of reasoning. PMID- 2245741 TI - The development of perspective taking: understanding differences in information and weighting. AB - 2 separate aspects of perspective taking are that judgments attributed to another should depend on the information available to the other (Information effect) and on how the other's use of information differs from one's own (Weighting effect). These 2 aspects of perspective taking were studied in a moral judgment task with preschoolers, and second and fifth graders. Subjects were read a series of stories about a little boy transgressing and asked to make judgments from both their own perspective and that of a mother character in the stories. The mother story character had either the same information as the subject or only partial information. Valence of intention and consequence and the amount of mother's knowledge varied factorially. Subjects were clustered using scores derived from the judgements. 3 clusters were found that showed different levels of perspective taking ability. There was a developmental progression in the 3 levels of perspective taking. Subjects in the Harshness cluster attributed harsher judgments to the mother perspective. Subjects in the Weighting cluster weighted information differently depending on the perspective from which they judged. Subjects in the Information-and-Weighting cluster weighted information differently depending on perspective, and also considered the amount of information available to the mother character in attributing judgments. The findings are compared to current theory on the development of perspective taking. Future research and theory need to consider the influence of both information and weighting differences on performance in perspective-taking tasks. PMID- 2245742 TI - Three-year-olds' problems with false belief: conceptual deficit or linguistic artifact? AB - Researchers are divided over whether young children understand other people's minds. This study reexamines the main technique used to show a basic inability in 3-year-olds to make judgments about a person's thoughts when that person's knowledge happens to be false. 131 children, aged 3, 3 1/2, and 4, were shown the real, unexpected contents of a chocolate box and were required to say what a friend would think was in it and what their own previous expectations had been. Success in this task was compared between the 3 age groups and also according to the specificity of questions asked. It was found, in contrast to previous findings, that test questions that are temporally specific and syntactically straightforward enable most 3-year-olds to attribute false beliefs to others. These results suggest that 3-year-olds' access to information about others' mental states is bounded by the linguistic demands placed upon them, but long before their fourth birthday children have some understanding of others' mind. PMID- 2245743 TI - Identification of alcohol by smell among preschoolers: evidence for early socialization about drugs occurring in the home. AB - This study tested preschoolers' ability to provide accurate verbal associations to alcoholic beverage odors and whether this ability was related to parental drinking patterns and motivations. Older preschoolers performed better than younger preschoolers; photographic cues improved performance; children who correctly identified a substance by smell had socially appropriate knowledge of the culturally appropriate users of the substance; children reported liking substances that are used mainly by children and adults, and generally reported disliking substances whose use is legally limited to adults only; children were better at identifying substances they commonly use, but success at recognition of alcoholic beverages was related to heavier parental drinking and use of alcohol for escape reasons. Findings have implications for theories of socialization to drug use and for models of prevention. PMID- 2245744 TI - Children's use of frames of reference in communication of spatial location. AB - The frames of reference used by 4-, 6-, and 8-year-old children were studied in a spatial direction-giving task. Children were asked to specify verbally the location of a toy hidden under one of several identical cups. The child and listener sat facing each other at opposite ends of a room that had distinctive or nondistinctive landmarks proximal and distal to the hiding location. Location needed to be specified with respect to either the left-right dimension, the front back dimension, or both. The results indicated that (1) although children's overall performance improved with age, communication about the left-right dimension was particularly difficult for 4-year-old children and showed a higher rate of improvement with age than communication about the front-back dimension; and (2) the frames of reference that children incorporated into their directions changed with age and differed for directions about the front-back and left-right dimensions. Both 4- and 6-year-old children used person references (themselves or the listener) to specify front-back relations, but only the 6-year-olds were able to compensate for their apparent difficulty in using the terms left and right by using landmarks to specify the left-right dimension. Eight-year-olds used a combination of person and landmark references in directions about both dimensions. Discrepancies between the frames of reference children used to communicate spatial location and those typically used in other spatial cognition tasks are discussed in terms of developmental and task constraints. PMID- 2245745 TI - Misconceptions about motion: development and training effects. AB - 2 experiments were performed to examine whether children and adults possess a single-object/single-motion intuition. This intuition involves the view that because all parts of a rigid object move together, they all must move at the same speed. We found that third graders, sixth graders, ninth graders, and adults all responded in accord with this intuition. On problems where the intuition led to errors, a large majority of subjects of all ages answered incorrectly. On problems where it led to successful performance, subjects answered more accurately than on problems where the intuition was not applicable. In addition, the specific errors were those that the intuition yielded, and the intuition fit individual patterns of performance. The intuition not only influenced speed judgments but also judgments of distance traveled. Experiment 2 demonstrated that making sixth graders aware of the intuition and providing them kinesthetic experience that contradicted it produced significant improvements in the children's understanding. Implications for how scientific misconceptions in general can be overcome were discussed. PMID- 2245746 TI - Do infants use their own images to locate objects reflected in a mirror? AB - The ability of infants to locate a toy from a mirror reflection was investigated in 3 experiments. In the first, it was found that a minority of 22-month-old infants turned to locate the toy that was the source of the reflection, and that localization of the toy occurred regardless of whether the infants' own image was visible in the mirror. The results of 2 further experiments indicated that younger infants aged 14 and 18 months rarely use mirror information to locate a toy. When they do so, they also turn whether or not images of themselves are visible. It is concluded that tasks involving the localization of objects or events from mirror images are not direct indices of self-recognition. Rather, they indicate the skill of infants in using the mirror as a perceptual tool. PMID- 2245747 TI - Contextual constraints on memory retrieval at six months. AB - In 3 experiments, 6-month-old infants learned to move a mobile by kicking and were tested 1 to 21 days later for retention of the newly acquired memory as a function of the training and testing contexts. In Experiment 1, decreasing the relative distinctiveness of the training and testing context did not impair retrieval of the newly acquired memory. In Experiment 2, however, testing in a different context completely eliminated retention after delays of 1 and 3 days, when retention was otherwise perfect; after progressively longer delays, retention improved paradoxically. The familiarity or novelty of the test context was not a factor in the failure of infants to recognize the mobile in the altered context after 1 day. In Experiment 3, the effect of an altered context was assessed in a reactivation paradigm. After the training memory was forgotten, infants were presented with the original mobile as a reminder and were tested for retention of the training memory 1 day later. When either the reminding context or the testing context was different, they exhibited no retention. These findings reveal that memory retrieval at 6 months is highly specific to the setting in which the memory is acquired. We propose that infants learn what specific events are associated with what specific places prior to the age when they can locomote independently and acquire a spatiotemporal map of the relations between those places. PMID- 2245748 TI - Preference for infant-directed speech in the first month after birth. AB - 2 experiments examined behavioral preferences for infant-directed (ID) speech over adult-directed (AD) speech in young infants. Using a modification of the visual-fixation-based auditory-preference procedure, Experiments 1 and 2 examined whether 12 1-month-old and 16 2-day-old infants looked longer at a visual stimulus when looking produced ID as opposed to AD speech. The results showed that both 1-month-olds and newborns preferred ID over AD speech. Although the absolute magnitude of the ID speech preference was significantly greater, with the older infants showing longer looking durations than the younger infants, subsequent analyses showed no significant difference in the relative magnitude of this effect. Differences in overall looking times between the 2 groups apparently reflect task variables rather than differences in speech processing. These results suggest that infants' preference for the exaggerated prosodic features of ID speech is present from birth and may not depend on any specific postnatal experience. However, the possible role of prenatal auditory experience with speech is considered. PMID- 2245749 TI - The effect of hearing impairment on the quality of attachment and mother-toddler interaction. AB - In the present study, 41 hearing impaired and 41 hearing toddlers together with their hearing mothers were observed in Ainsworth's Strange Situation and during free play. Both security of attachment and ratings of maternal and toddler behavior during free play were remarkably similar for the hearing impaired and hearing dyads. In addition, security of attachment was related to the ratings of maternal and toddler behavior in a similar way for the hearing impaired and hearing toddlers. The results suggest that development of a secure attachment and maintaining a good mother-toddler relationship does not depend on normal language development during the toddler years. PMID- 2245750 TI - The social competence of children born prematurely: effects of medical complications and parent behaviors. AB - 36-month-old, full-term children (n = 21) and low-birthweight (LBW) children of high (n = 25) and low (n = 23) medical risk status were observed in interactions with mothers in teaching and social context. Child compliance, self-directed behaviors, and problem behaviors were evaluated as well as associations among aspects of children's social competence, mothers' behaviors, and context factors. Degree of medical risk was associated with impairments in children's self directed behavior and quality of response to maternal directives. Mothers of LBW children showed a smaller proportion of behaviors that provided choices compared to mothers of full-term children. Medical complications, children's cognitive status, and mothers' interactive behaviors were significantly associated with LBW children's social competence. Results of regression analyses suggested that mothers and LBW children influence each others' behavior in ways similar to mothers and full-term children in both teaching and social contexts. PMID- 2245751 TI - Does infant carrying promote attachment? An experimental study of the effects of increased physical contact on the development of attachment. AB - This study was designed to test the hypothesis that increased physical contact, experimentally induced, would promote greater maternal responsiveness and more secure attachment between infant and mother. Low-SES mothers of newborn infants were randomly assigned to an experimental group (n = 23) that received soft baby carriers (more physical contact) or to a control group (n = 26) that received infants seats (less contact). Using a transitional probability analysis of a play session at 31/2 months, it was demonstrated that mothers in the experimental group were more contingently responsive than control mothers to their infants' vocalizations. When the infants were 13 months old, the Ainsworth Strange Situation was administered. Significantly more experimental than control infants were securely attached to their mothers. We infer from these results that for low income, inner-city mothers, there may be a causal relation between increased physical contact, achieved through early carrying in a soft baby carrier, and subsequent security of attachment between infant and mother. PMID- 2245752 TI - Minor parenting stresses with young children. AB - The importance of major life stress and minor daily hassles associated with parenting was studied in 74 mothers and their 5-year-old children. Of interest were the relative and absolute contributions of the stress factors to indices of parental, child, and family functioning. Mothers completed questionnaires regarding stressors, aspects of parenting and individual psychological status, social support, family functioning, and child behavioral status. Mother-child pairs were also observed in interactions in a laboratory setting. Analyses indicated that life stress and parenting daily hassles significantly predicted aspects of child, parent, and family status. Hassles, however, proved to be a more powerful stress construct. Further analyses indicated that mothers' social support moderated the influence of hassles on indices of maternal behavior. The results are discussed in relation to the potential for minor parenting stresses to influence microsocial processes within parent-child relationships and contribute to dysfunction in children and families. PMID- 2245753 TI - Maternal self-efficacy: illusory control and its effect on susceptibility to learned helplessness. AB - 66 mothers of 5-month-old infants participated in 2 simulated child-care tasks to examine differences in response to the performance demands of child care. Mothers first participated in a task in which they estimated their perception of control over stopping an audiotaped infant cry (illusion of control). 1 week later, they participated in another task to assess their ability to learn effective responses in stopping the cry (susceptibility to learned helplessness). Mothers with a high illusion of control differed from mothers with low or moderate illusory control by showing increased susceptibility to helplessness. Physiologically, mothers with low and moderate illusory control showed attenuated and "attentive" heart rate responses to the impending cry, respectively. Mothers with high illusory control were "inattentive", with mothers of difficult infants in that group responding "defensively". Our data suggest that high illusion of control may be a maladaptive response to the performance demands of child care. PMID- 2245754 TI - Mutagenic activity of paracetamol. A study conducted on volunteers. AB - The mutagenic activity of paracetamol (PC) was studied on a group of healthy persons (3 men, 8 women) after the simultaneous administration of 3 X 1000 mg of PC and an identical dose of PC + 1000 mg of ascorbic acid within a period of 8 hours. Blood sample tests were made at intervals of 0, 24, 72 and 168 hours. A cytogenetic analysis showed that in 24 hours PC had increased the aberrant cell frequency to 2.77 +/- 0.37 per cent as distinct from 1.68 +/- 0.30 per cent (p less than 0.05) prior to the drug. In 72 hours, the rate of buccal mucosa micronuclei had risen to 0.38 +/- 0.07% against 0.19 +/- 0.06% prior to PC (p less than 0.01). Unscheduled DNA synthesis in peripheral lymphocytes had dropped to T/C = 2.06 +/- 0.54 (p less than 0.01) against 3.16 +/- 0.84 before PC. The lipid peroxidation level in the plasma remained unchanged. Ascorbic acid administered simultaneously with PC had no effect on the changes observed. A further follow-up of other PC side effects is recommended. PMID- 2245755 TI - Surgical procedure and results of implantation of the Czech cochlear neuroprosthesis. AB - A special surgical procedure was developed for the implantation of the Czech single-channel extracochlear neuroprosthesis. The implantation was performed in four adult, postlingually deaf subjects. In one patient a successful reimplantation was performed. The authors assess the implant patients' ability to differentiate changes in simple stimulation signals. PMID- 2245756 TI - Therapeutic methods of digestive endoscopy in persons of advanced age. AB - Towards the end of 1988, 85 out of 170 patients indicated for endoscopic papillotomy (EPT) were over 65 years of age, and, of these, 54% were 75 and more. EPT was successful in 90.6% of those over 65. Total morbidity was 4.7% and mortality 1.2%. Endoscopic colorectal polypectomy (EPE) was performed during the same period in 591 subjects. 143 of them (24.2%) were over 65 and had a total of 284 polyps removed. Almost half those polyps were more than 10 mm in diameter. Adenomas of the right colon were at least 3 times as frequent as in asymptomatic subjects aged 45-60 years revealed by screening for colorectal neoplasms in HaemocultR-positive subjects. Particular attention was devoted to patients with malignant polyps and with very broadly sessile adenomas--both could definitively be treated with the endoscopic method. EPT is often the only possible therapy for elderly and high-risk patients. Every colorectal polyp should be evaluated by endoscopy, and EPE, especially in patients of advanced age, is the method of choice when technically feasible. PMID- 2245757 TI - Results of screening for colorectal carcinoma in the District of Bruntal using the Haemoccult Test in 1985-1988. AB - In 1985-1988, 11,046 working people of the district of Bruntal, aged 45-69, were examined for occult bleeding into the stools, using the Haemoccult test. The return rate of the tests was 92.05%. Screening detected 241 patients (2.18%) with positive stools test results who were referred to further examination. 129 patients (1.17%) were found to have one or more adenomatous polyps or adenocarcinoma in the large intestine. Adenocarcinoma was detected in 15 cases (0.13%): eight in stage Dukes A, two in stage Dukes B, three in Dukes C, and two in Dukes D stages. Endoscopic polypectomy or surgical operation were used for treatment. The programme of screening for colorectal carcinoma as elaborated for the low-risk group of asymptomatic subjects over 45 years of age helps to detect less advanced stages of this oncological affection. PMID- 2245758 TI - Different activities of energy metabolism enzymes in children's cardiac atria and ventricles. AB - Tissue samples from the right atrium and ventricle of the same heart were obtained during surgery on 45 children operated on for congenital heart disease (tetralogy of Fallot, ventricular septal defect). Significant enzyme activity differences were found between atrial and ventricular muscle. Aerobic metabolism enzymes (citrate synthase, malate dehydrogenase), with lactate metabolism (lactate dehydrogenase) and fatty acid oxidation (hydroxyacyl-SoA dehydrogenase) showed significantly higher activities in ventricular muscle tissue. In contrast, hexokinase, the enzyme responsible for glucose phosphorylation was significantly higher in the atria. Hence, the right ventricle can utilize and oxidize to the full all the main nutrients (fatty acids, glucose and lactate) while the right atrium utilizes primarily glucose. These atrio-ventricular differences are independent of the type of congenital heart disease and their existence can be presumed in healthy persons, too. PMID- 2245759 TI - Deficiency of interferon production in children with recurrent respiratory diseases. AB - In 50 children followed-up for frequent and repeated respiratory diseases, IFN alpha production was examined. The ability to produce IFN-alpha correlated with the clinical situation of the children. It was low in children constantly ill and better or even normal in children whose health substantially improved or who were without symptoms during the last two years. The influencing of IFN-alpha production probably could have a favourable effect also on the clinical development of the disease. PMID- 2245760 TI - The gnathic system in obese and diabetics. I (Basic relationship of function and form). AB - The authors pay complex attention to the research of the gnathic system, focused first of all to the mechanical interactions towards solid formations of the gnathic system. The results of their analysis show, that in the first cell already differentation to tensile functions of the membrane and compressive functions of its contents (cytoplasm) exists. In the osseous tissue the mechanical strain is also distributed to different substances, reacting differently to the mechanical stress according to their aggregate state--the liquid state secures an equal distribution of the developing compression, the collagens intercept and cushion the arising traction, and the mineral component the oriented compressions. Therefore, the bone tissue markedly differs from the inorganic homogenous solid substances, where the distribution of the mechanical strain is different. A detailed analysis shows that the form and structure of the bones is in accord with the course of the developing compressive strain and dependent on the mechanical consistency of the consumed food. PMID- 2245761 TI - Transplantation of the kidneys in diabetics. AB - Diabetic nephropathy affects half the type 1 diabetics and is the most frequent cause of death there. While in some countries diabetics account for 25-30% of all patients newly admitted in dialysis and transplantation programmes, in Czechoslovakia the number of diabetics treated by dialysis or transplantation is small. From August 1985 to June 1988, 15 isolated kidney transplant operations were performed on 13 diabetics with serious late complications of diabetes. By the time of writing, all recipients had been surviving (for 1 up to 35 months), and only two were receiving artificial kidney treatment. Progressive vascular complications were in two cases the cause of gangrene of the lower extremity, one patient had a central cerebrovascular attack. Despite this, successful transplantation resulted in a marked improvement of the patients' general condition and quality of life. Due to intensified insulin therapy, diabetes, too, was satisfactorily compensated in the majority of the recipients. As experience so far indicates, if the patient is prepared in good time, which includes diabetological, nephrological and ophthalmological treatment, the results of transplantation in diabetics can be comparable to those achieved in non-diabetic patients. Renal transplantation in diabetics should be developed in all transplantation centres in Czechoslovakia, and uraemic diabetics should not be eliminated from the dialysis-transplantation programme except in cases of serious contraindication. PMID- 2245762 TI - Human recombinant erythropoietin in the treatment of anaemia in chronic haemodialysis patients. AB - Five women aged 50-64 years with chronic renal failure caused by interstitial nephritis, maintained by chronic haemodialysis, were treated for three months with human recombinant erythropoietin. The blood haemoglobin level roce from 78.0 +/- 6.9 g/l to 108.4 +/- 15.5 g/l, haematocrit from 21.8 +/- 1.8% to 33.6 +/- 4.8%, and the rate of reticulocytes 1.8% to 4.9%. Serum ferritin concentration declined from 2213 +/- 1982 micrograms/l to 850 +/- 953 micrograms/l. Unlike the pre-treatment period, no blood transfusion had to be given during the administration of erythropoietin. The patients' general condition improved. There were no serious complications. The action of erythropoietin persisted for two months. Human recombinant erythropoietin is a significant help in the treatment of patients with chronic renal failure. PMID- 2245763 TI - [The incidence and localization of colorectal adenomas and carcinomas in 4109 patients]. AB - Findings at coloscopy were analysed retrospectively for 4109 patients (2257 women, 1852 men; mean age 62.3 [5-100] years) who had undergone a high coloscopy between 1982 and 1987. The aim was to determine the site of colorectal adenomas and carcinomas, as well as the relationship between adenoma and carcinoma. Main indications for the coloscopy were polyps at previous ambulatory endoscopy (15.4%), abdominal pain (11.3%) and changed bowel habits (11.2%). In 752 patients 1273 adenomas were detected and in 354 patients there were 374 carcinomas (333 solitary, 21 multiple). 21.6% of the adenomas and 21.4% of the carcinomas were proximal to the right flexure. In 75 of 177 patients (42.4%) with both adenoma and carcinoma both tumours occurred in the same intestinal segment. The severity of the dysplasia increased with increasing size of the adenoma. 52 adenomas (4.1%) already had evidence of malignant degeneration. But 7.7% of the adenocarcinomas were only 5-10 mm in diameter. The increasing incidence of right sided tumour (right shift) compared with the hitherto known distribution pattern argues for total coloscopy as the primary procedure in the diagnosis of colorectal tumour. PMID- 2245764 TI - [Hyperprolactinemia in malignant lymphomas]. AB - Serum prolactin levels at the time of confirmed diagnosis and of remission were determined prospectively in 36 patients (22 males, 14 females; mean age 54.2 [18 77] years), 12 with Hodgkin and 24 with non-Hodgkin lymphoma. Basal prolactin levels were elevated to a mean of 1900 (720- greater than 4000) mU/l in 12 patients. Eight of these had extranodal manifestations of lymphoma. At the time of remission the elevated prolactin levels had returned to normal in six patients. The cortisol concentrations of the 36 patients did not correlate with the prolactin levels so that stress-induced increase in secretion seems unlikely. These results point to prolactin possibly playing a role as a nonspecific tumour marker. In addition, lymphomas should be included in the differential diagnosis of hyperprolactinaemia. PMID- 2245765 TI - [Eosinophilic fasciitis (Shulman's syndrome)]. AB - A 36-year-old man had noted a firm and painful swelling of the upper and lower limb, increasing over the previous few weeks. He had no fever, but the erythrocyte sedimentation rate was slightly increased (20 mm in the first hour). In addition there was a mild normochromic, normocytic anaemia (13 g/dl) and thrombocytosis (517,000/microliters). Gamma-globulin fraction was raised to 26%. The blood eosinophilia of 44% and the histological findings in a wedge biopsy of the lower leg (oedematous widened connective tissue septa, inflammatory infiltrate with eosinophilic granulocytes) established the diagnosis of eosinophilic fasciitis (Shulman syndrome). During oral treatment with prednisone (100 mg/d) the clinical symptoms regressed and the eosinophilia in peripheral blood disappeared. In the course of the subsequent seven months the prednisone dose was reduced gradually to 10 mg daily. But, because the symptoms did not entirely disappear the prednisone dose had to be increased temporarily for four times until there was a further, stepwise, reduction of the symptoms. But mild induration of the lower leg persisted. Maintenance treatment with prednisone, 10 mg daily, has been continued in order to avoid recurrence. PMID- 2245766 TI - [Successful drug therapy in Aspergillus endocarditis]. AB - A 74-year-old man who had a weight loss of 7 kg in three months, with fever up to 38 degrees C and anaemia (Hb 9.4 g/dl) began to have pain and blue discoloration of fingers II-V of the right hand. Echocardiography demonstrated vegetation on the aortic valve cusps and blood culture grew Aspergillus fumigatus, indicating Aspergillus endocarditis. There were no predisposing factors. Valve replacement was contraindicated because of the age of the patient, the presence of peripheral arterial disease, and previous myocardial infarction. Treatment was started with amphotericin B i.v. (dosage increasing to 50 mg daily) and 1.5 g daily of flucytosine by mouth, to a total of 1.1 g amphotericin B and 41.5 g flucytosine in five weeks. During this time there was a gradual decrease in symptoms and the valve vegetations. Nine months later there has been no recurrence. PMID- 2245767 TI - [The diagnostic possibilities in arthroscopy of the knee joint]. PMID- 2245768 TI - [The therapy of myelodysplastic syndromes]. PMID- 2245769 TI - [Legal problems in connection with electronic data processing in medical practice]. PMID- 2245770 TI - [Diagnosis in facial pains]. PMID- 2245771 TI - [Ovarian cysts in cattle--etiology, therapy success, fertility]. AB - The functions of the ovaries were controlled in 92 cattle over a period of 12 to 95 days p.p. Cystic follicles developed in 61% (25 from 41) during reconvalescence period and were correlated with a 4.2 days earlier onset of ovarian function, which was assured statistically. All together in 41 animals cystic degeneration was registered. Cysts having appeared before day 39 p.p. receded spontaneously in 24%, those having developed later remained. By application of the GnRH-analogous Buserelin (Receptal), either exclusive or combined with beta-carotene or Prostaglandin Trometamol-Tiaprost (Iliren) ovarian function could be restored in all cases. Restitution was most rapid when using Buserelin plus beta-carotene (Fertilizing insemination 3 weeks post application), but protracted after the consecutive method of therapy. All 92 cattle became pregnant. The P4-level of all "cyst-cows" were low, i.e. between 0.68 and 0.81 ng/ml of skimmed milk. The increase of conductivity of the cervical mucus to above 30 Ohm turned out an evidence of an ovarian cyst to be present. Restoration took longer in correlation with the increasing diameter of the cysts. PMID- 2245772 TI - [Concentration of IGF-I and estradiol-17beta in the blood plasma of pregnant cattle]. AB - Blood samples were collected from pregnant cows, heifers and also from non pregnant cows serving as controls. The determination of insulin-like-growth factor-I (IGF-I) and estradiol-17 beta (E2) were performed immunologically. In the non pregnant cows E2 remained unchanged. IGF-I decreased around parturition and increased again commencing the 6th week of lactation. Compared to nonpregnant animals E2 but not IGF-I was slightly elevated during the first 10 weeks of pregnancy. During the 10th up to 20th week of pregnancy the mean values of IGF-I were increased as well as the ones of E2. During the late pregnancy the values of IGF-I in heifers are obviously more elevated as in lactating pregnant or non pregnant cows; analogous high values were determined in pregnant cows only during the dry period. Before parturition even a negative correlation exists between IGF I and E2. It is concluded that IGF-I is predominantly regulated by other factors. PMID- 2245773 TI - [Effects of partial drying of an udder quarter in cows with teat injuries]. AB - In cows with teat lesions, partial drying-off of the affected mammary quarter is recommended for a period of 3 to 10 days. The other three quarters are normally milked. Partial drying-off reduces the risks of complications due to the daily milking. The slight reduction of milk production, connected with the temporary drying-off a single quarter, is nearly compensated within 4 weeks. PMID- 2245774 TI - [Metaphylaxis of puerperal disorders in cattle]. AB - The effects of metaphylactic measures in cattle herds with the aim of diminishing puerperal disturbances and ensurement of high reproductive performance were studied. About 5000 cows in more than 30 groups (experimental and controls) were included into the clinical investigations. Dietary supplementation by sodium propionic acid over a period of 4 weeks, oxytocin or parasympathomimetics administered during the first 3 days post partum had a certain metaphylactic effect, only when the therapeutic principle met the prevalent cause of the given puerperal disturbance. In herds with high incidence of noninfectious retention of fetal membranes the metaphylactic application of Se and Vitamin E (10 days ante partum) can be taken into account. Stimulation of the ovarian activity by GnRH is recommended in animals which fail to have developed follicular activity by the 12th-15th day post partum. PMID- 2245775 TI - [Recovery and light microscopic evaluation of follicular oocytes of swine and relationship between the degeneration rate of oocytes and the estrus phase]. AB - Cumulus-oocyte complexes were recovered from 25 gilts by aspiration of follicular fluid or cutting of follicles from all Graafian follicles of greater than or equal to 3 mm in diameter during diestrus, proestrus or estrus. In 5 gilts the oocytes were collected post ovulation by flushing of oviducts. The recovery rate of follicular oocytes differed between 75.5% during the late diestrus (days 13 17) and 43.5% during the proestrus (days 18-21). During the proestrus and on day 1 of the estrus the recovery of oocytes was more difficult as a result of the higher viscosity of follicular fluid and the mucification of cumulus-oocyte complexes. The degeneration rate of oocytes was high during the diestrus with a peak at the time of regression of corpora lutea. From diestrus to the estrus the degeneration rate decreased. Following degeneration rates were found in the oocytes during the cycle: days 7-12: 38.8%, days 13-17: 50.0%, days 18-21: 29.6%, day 1 of the estrus: 10.8%, day 2 of the estrus ante ovulation: 11.8%, day 2 of the estrus post ovulation: 6.2%. Signs of degeneration were: Loss of cumulus cells (during diestrus and proestrus), damaged zona pellucida, enlargement of perivitelline space, deformation of oocyte, alteration of structure of the ooplasm, diameter of vitellus less than 100 microns. It was concluded that the selection of dominant follicles takes place in pigs during a long time of the cycle, especially during the diestrus. There were not any indications of a 2-wave hypothesis of follicular growth during the cycle in pig. PMID- 2245776 TI - [Toxic elements in the sex organs of the cow and their relationship to fertility]. AB - The content of heavy metals (Cd, Hg, Pb, Cr, Cu and Zn) has been determined by atomic absorption spectrophotometry in parts of genital organs of cows with and without reproductive disorders, in blood, in placenta, in colostrum, and in the calf blood. The samples were collected in an industrially polluted area and in a relatively non-polluted area. It has been proven in the group of 99 cows that the biological quality of the oestrous cervical mucus is also influenced by toxic elements. The best conception rate after the artificial insemination (80.0%) has been found in cows with the cervical mucus without spermiotoxic properties. The genital organs of 49 cows culled because of reproductive disorders were examined. No significant differences in the content of heavy metals have been found in the separate parts of genital organs. There were also no differences between the cows with and without reproductive disorders. Toxic elements in blood have been found in cows after parturition and in newborn calves both in the polluted and the non polluted areas. However, significant differences (p less than 0.01) were determined only in the content of Cd and Zn. The average content of all determined toxic elements in the samples of placenta in pluriparous and primiparous cows from the polluted and non-polluted areas was approximately at the same level. The content of Zn was 4.3 times higher than the hygienic standard in the colostrum of cows from the polluted area. The content of Zn exceeded the hygienic standard also in the non-polluted area, and the content of Cd and Hg was close to the hygienic standard there. PMID- 2245777 TI - [Rapid diagnosis of botulism in cattle using heated microcomplement fixation reactions]. AB - Clostridium botulinum toxin, type C, could be demonstrated by means of temperature induced microcomplement fixation in blood serum and in aspirated rumen fluid of cattle suffering from botulism. The results were already available after seven hours. Botulinum toxin likewise could be identified from hair of a suspicious carcass. The investigations confirm the high sensitivity of this method. PMID- 2245778 TI - [The development of iron and copper concentrations in blood plasma of calves in the first days and weeks of life, equally a contribution to the larvaceous neonatal iron deficiency anemia]. AB - Newly born calves (n = 93) were examined to determine the iron and copper values in the blood plasma. The investigation was divided into two sections: 1. Chronic measuring of the parameters of live-born calves until the sixth week (n = 48). 2. Short-time examination of newly born calves with different vitality figures/levels of vitality until the second day of life (n = 45). Iron and copper were determined by means of an inductively-coupled-plasma emissions-spectral analysis (ICP). In the case of a normal birth and vitality criteria calves are born with a plasma concentration of 27.7 +/- 9.6 mumol/l iron and 4.8 +/- 1.7 mumol/l copper. During the first few hours of life the iron concentration drops considerably and significantly (p less than or equal to 0.01) and rises again before the second week. There is a short period of considerable depression in the iron concentration. The copper values, in contrast, increase linearly and significantly (p less than or equal to 0.001) form the birth onwards until the end of the first week, then remaining on a high level. In the dynamic of the iron plasma curve the influence of race/breed is also evident. Calves of the race DFV have a significantly higher iron level than the DSB and DRB race (p less than or equal to 0.01) at the end of the sixth week of life. About a fifth (18.8) of the test animals in the first part of the investigation already had a hidden sideropenia (16.1 +/- 1.9 mumol/l) when they were born. Their iron concentration developed only slowly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245779 TI - [Sonographic findings of the mammary papilla of cattle]. AB - Morphological structures of the bovine Papilla mammae can be differentiated with portable ultrasound units and 5 MHz linear arrays. For practical use it is possible to scan the teat in a water-filled plastic cup as a kind of water delay system. The visualization of pathological findings shows a possibility to evaluate this method as a diagnostic tool for the bovine teat. PMID- 2245780 TI - [The diagnostic and prognostic significance of ketonuria in fertility disorders of cattle]. AB - The diagnostic and prognostic significance of ketonuria for the prognosis of reproductive disorders in high-performance dairy cows was examined in 3 herds of Holstein Friesian and Holstein Friesian x Hungarian Red Pied F1 that were either primiparae or were due to calve for the 2nd to 8th time during the study period from mid-February to late March, 1988. The course of uterine involution and status of the ovaries was followed up by regular rectal and vaginal examination. In the first experiment (n = 15) the return of cyclic ovarian activity was monitored by determination of progesterone in milk twice weekly over a period of 10 weeks post partum. In the second experiment (n = 121) urine and milk samples were collected at intervals of 5 to 8 days over a period of 9 weeks post partum and analysed for ketone bodies. The body condition of the cows was estimated by a scoring system at 5 and 9 weeks post partum. In the third experiment (n = 289) urine samples taken 1-4 days before as well as 3 days and 5 weeks after calving were analysed for ketone bodies. Biologic reproduction data were followed up for 150 days post partum in all experiments. One to two thirds of the cows in the examined herds showed ketonuria post partum, some animals also displayed ketonuria ante partum. Persistent postpartal ketonuria occurred mainly among the older cows with a high performance that at the same time showed a marked loss of body condition during the first weeks post partum. Primiparous heifers seldom developed ketonuria, despite a generally poor body condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245781 TI - [Effect of 3,4-dihydroxybenzylamine (DHBA) on the myometrium of cattle in vitro]. AB - The effect of 3,4-DHBA was tested in vitro on strips of cattle myometrium. It was discovered that adding DHBA to non-contracting strips of myometrium, clear contractions can be induced. With spontaneously weakly contracting strips addition of DHBA further strengthens the contractions. With irregular contraction forms a coordination of the contractions can be achieved. The optimal effective doses is 5.1.10(-6) mmol DHBA/ml of the nutrient solution. PMID- 2245782 TI - [Important virus infections of the respiratory tract in cattle from the clinical point of view]. AB - The etiological participation of different viruses in the pneumonia complex of cattle is undisputed. The significance of the individual viruses in the genesis of disease symptoms is still mostly unclear. Since the pneumonia complex of cattle is a multifactorial syndrome, vaccination programs as the only measure of prophylaxis in most cases do not show the desired effect. Against those viral agents causing self-standing diseases of the respiratory tract, specific vaccinations are applicable with success. Prerequisite for their effectiveness, however, is the exact etiological clarification of the cause of disease or of the existing infections respectively in the herd. The frequency of possible viral agents in infections of the respiratory tract in cattle from herds of the province of Schleswig-Holstein found in routine diagnostic work during the last four years is presented in addition. PMID- 2245783 TI - [Epidemiologic studies of the detection of viral infection agents in calf losses in the Weser-Ems region]. AB - In 961 calves up to an age of 6 months which were sent to the animal health center in Oldenburg between March 1987 and March 1990 for necropsy the results of determination of different viruses were calculated: BVD-, rota-, corona-, parainfluenza-3- (PI-3)-, bovine herpes-1 (BHV-1)- and bovine respiratory syncytial virus (BRSV). In 122 and 104 randomly collected health calves of 22 farms antibodies against BRSV and bovine adeno virus-types 5, 7 and 8 were determined. 50.1% of the necropsied calves were one and two weeks old. In this group in 40.2% rotavirus and in 19.0% coronavirus could be isolated. All over the calves the frequencies of isolated viruses were 13.3% for BVDV, 4.6% for BRSV, 3.2% for BHV-1, and 2.1% for PI-3. The percentages of positive findings for rota- and coronavirus increased up to 7 days after birth, and thereafter both decreased. The frequencies of BVDV and BRSV were higher in older groups. The frequency of PI-3 was low and remained constantly. Infections with rota-, corona- and with both viruses were accompanied by BVDV in 11.3, 5.3 and 14.3%, respectively. Against bovine adenoviruses and BRSV in the first 8 weeks and after 14 weeks of life in more than 70% of the calves antibodies were detected. PMID- 2245784 TI - [Transplacental BVD virus transmission after experimental inoculation of goats in different pregnancy stages]. AB - Eight groups of altogether 25 goats without neutralizing antibodies against BVD virus, were inoculated either intranasally or intranasally and subcutaneously with two different BVD virus isolates during different stages of gestation. In all 18 goats inoculated within the first 78 days of gestation an abortion and foetal death rate of approximately 100% occurred. Only one goat gave birth to a clinically healthy kid. The other seven goats which were inoculated after the 78th day of gestation showed also a high foetal death rate. Only two of them gave birth to clinically healthy kids. Neutralizing antibodies against BVD virus could be detected in blood samples drawn from 14 kids born at normal term including stillborn and non-viable offsprings. BVD virus was reisolated from different organs taken from seven foetuses. It was not possible to isolate BVD virus from any of the normal offsprings. PMID- 2245785 TI - [Veterinary verdict in a damage case, resulting from an unnecessary gynecological treatment of a mare]. AB - A malpractice caused a reduction in the value of a 15 years old mare, however the owner of the mare had not given the veterinarian the chance to reduce the injury and his claim of damages was unrealistically high. PMID- 2245786 TI - [Boogenic human diseases]. AB - Basing on observations from practice and clinic, a survey is given (in two tables) concerning the disturbances of human health due to the handling of cattle, and their causes. PMID- 2245787 TI - [The effect of gonadotropin releasing hormone (GnRH) and analogs on the conception rate in cattle. A critical literature review]. AB - The objective of this article was to review the current literature of the influence of gonadotropin releasing hormone (GnRH) and GnRH agonists on conception rate in dairy cattle. The application of GnRH or agonists at artificial insemination (first and subsequent) and between days 7 and 34 after parturition were considered. The variations between studies were discussed as well as different mechanisms concerning the influence of GnRH for establishing pregnancy. From a critical point of view the routine use of GnRH or agonists at the time of first or subsequent breeding or during the postpartum period cannot be supported. PMID- 2245788 TI - Antagonism among Bacteroides fragilis group strains isolated from middle ear exudates from patients with chronic suppurative otitis media. AB - The production and sensitivity of a bacteriocin-like substance in Bacteroides fragilis group strains isolated from middle ear exudates in children with suppurative otitis media were studied through antagonism assayed by the well method. The results of the crossed reactions showed that 10 strains (66.6%) were bacteriocinogenic, 9 were sensitive to at least 1 bacteriocin (60%), and none showed inhibitory activity against homologous strains. Different patterns of susceptibility to bacteriocin-like substances were observed among strains isolated from the same patient as well as different strains isolated from another patient. These findings indicate that bacteriocin typing of anaerobic bacteria isolated from middle ear exudates in children with otitis media might have use in epidemiologic studies. PMID- 2245789 TI - Otolaryngic manifestations of myiasis. AB - Although rare in North America and Europe, myiasis is seen occasionally in tropical and undeveloped countries. This disorder results from the penetration of a fly larva into a part of the human body, and it causes various symptoms in the host. The exposed areas of the skin are the ones predominantly affected and the eyes, ears, nose, and paranasal sinuses are less commonly affected. We review our experience with 12 patients with myiasis of the ears, nose, and paranasal sinuses. PMID- 2245790 TI - Chemodectoma of the larynx. AB - Chemodectomas of the larynx are rare tumors. Only 35 cases were reported in the literature prior to the publication of this paper. We report a further case and discuss the problems associated with hemorrhage during surgery. PMID- 2245791 TI - Chondrosarcoma of the sphenoethmoid complex. AB - Chondrosarcoma of the nose and paranasal sinuses is extremely rare. We report a case of a child with a massive chondrosarcoma of the sphenoethmoid complex who presented with a change of visual acuity. Clinical and histologic characteristics of this lesion are discussed, along with treatment options and factors affecting prognosis. PMID- 2245792 TI - Epithelial myoepithelial carcinoma of the parotid gland. AB - EMEC is a clear-cell tumor of salivary gland origin. Since it was first recognized as a distinct salivary gland malignancy in 1956, sporadic cases have been reported. A case of an EMEC in a parotid gland of a 77-year-old man is described. The clinical and histopathologic features of this unusual neoplasm, as well as a description of the immunohistochemistry and current management of this uncommon entity are presented. PMID- 2245793 TI - Chronic cough due to angiotensin-converting enzyme inhibitors. AB - The ACE-inhibiting drugs enalapril and captopril may result in a chronic and sometimes severe cough for which no pathologic cause can be found. Drug-induced cough should therefore be considered in any symptomatic patient taking these medications. In such cases, prompt withdrawal of the drug and substitution of a non-ACE inhibitor is curative and conserves the time and resources of the patient and the physician by avoiding unnecessary diagnostic and therapeutic measures. PMID- 2245794 TI - Chondrosarcoma of the mandible. PMID- 2245795 TI - Primary malignant melanoma of the nasal cavity. PMID- 2245796 TI - Dysphonia associated with factitious asthma. PMID- 2245797 TI - Indeterminate salivary fistula through the external auditory canal. PMID- 2245798 TI - Dermoid cyst of the submandibular area. PMID- 2245799 TI - Sucralfate and nasal synechiae. PMID- 2245800 TI - Neonatal monosodium glutamate abolishes corticotropin-releasing factor-induced epileptogenic activity in rats. AB - Intracerebroventricular (i.c.v.) injection of rat corticotropin-releasing factor (rCRF) at doses of 5-20 micrograms in rats induces epileptogenic activity characterized by pacemaker-like spikes localized in the hippocampal leads. Such an effect was still present in rats neonatally treated with saline but was absent in those neonatally treated with monosodium glutamate (MSG), a treatment that caused marked changes in the concentration of several brain neurotransmitters and neuropeptides in hypothalamic nuclei where CRF is highly concentrated and is believed to induce endocrinologic and behavioral effects. The present results suggest the rCRF-induced spiking activity is mediated by activation of neuronal pathways sensitive to MSG neurotoxic effect. PMID- 2245801 TI - Triiodothyronine and brain excitability. AB - We investigated mechanisms involved in thyroid hormone action on brain excitability. The effect of acute exposure of triiodothyronine (T3) to rat hippocampal slices in vitro was studied. No significant changes could be detected in prevolley, field excitatory postsynaptic potentials (fEPSP) and population spike amplitude, while there was a minor, nonsignificant trend toward shortening of the population spike latency time. T3 had no effect on penicillin-induced epileptiform activity. There was, however, an active accumulation of radioactively labeled T3 in the slices. A rat cervaux-isole preparation was used to determine focal seizure thresholds in the visual cortex, and no acute (2-4 h) effects were demonstrated. No significant acute effects of T3 on brain excitability in the hippocampus and visual cortex was observed, despite an active accumulation of T3. Thus, the effect of T3 on brain excitability most likely is due to delayed effects. PMID- 2245802 TI - Epidemiology of epilepsy in Guaymi Indians from Bocas del Toro Province, Republic of Panama. AB - This cross-sectional study was conducted to describe the epidemiology of epilepsy in Guaymi Indians residing in Changuinola, a small town on Panama's Caribbean coast near Costa Rica. We randomly selected households and attempted to enroll all residents aged less than or equal to 1 year; 337 eligible subjects agreed to participate (93% response rate). We administered a standard neurologic disease screening examination to all subjects and, if any abnormality was found, we administered a standard neurologic evaluation. We detected 19 cases of active epilepsy; the mean age at onset was 12 years, and generalized tonic-clonic seizures were the most common diagnosis (10 of 19, 53%). The prevalence of active epilepsy among Caribbean coastal Guaymi (57/1000) is considerably greater than that in lower class Panama City populations (22/1000) or in other parts of the world. To identify risk factors for epilepsy, we collected epidemiologic data and serum (for Cysticercus antibody) from subjects with active epilepsy and from 44 age/sex-matched controls. Significantly more cases (47%) than controls (6%) had other family members with epilepsy (relative risk, RR = 14); 44% of cases and 13% of controls reported a history of febrile seizures during childhood (RR = 6). PMID- 2245803 TI - Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy. AB - The relationship between focal disturbances of glucose utilization demonstrated by positron emission tomography (PET) and electrophysiologic abnormalities defined by intraoperative electrocorticography (ECoG) was studied in eight children (aged 13 months to 12 years) who underwent cortical resection because of intractable seizures. None of the children had pure temporal lobe epilepsy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were normal in four of the eight children. The scalp electroencephalogram (EEG) showed lateralized interictal epileptiform abnormalities in all eight and lateralized ictal onset in five of eight. In seven children, interictal PET showed focal hypometabolism; the eighth child had focal, ictal hypermetabolism. ECoG at the time of surgery showed epileptiform spiking, slowing, and/or suppression of normal background activity that in every case corresponded to the focus on PET scan. The ECoG findings support the notion that in children with epilepsy focal metabolic abnormalities on PET correspond to electrophysiologically abnormal areas of cortex, which are presumably also the epileptogenic regions. Such areas can appear normal on anatomic imaging studies (CT and MRI). When ictal scalp EEG data are ambiguous or contradictory, PET provides a less invasive means than chronic grid or depth electrode recording for evaluating whether a localized epileptogenic area exists. PMID- 2245804 TI - Lateralized effects of subclinical epileptiform EEG discharges on scholastic performance in children. AB - The interaction between lateralization of subclinical epileptiform discharges and cognitive tasks was investigated in 21 children (12 girls and 9 boys, mean age 10.6 years). Seventeen had a diagnosis of epilepsy (partial or secondarily generalized). Testing was by reading, arithmetic, and intelligence subtests during continuous telemetric EEG and video monitoring. Children with left-sided discharges had significantly lower reading performance than children with right sided discharges. During reading, epileptiform discharges occurred relatively less frequently and with a shorter total duration over the left hemisphere than the right. This supports the view that cognitive tasks suppress epileptiform discharges when they activate a region of the brain within the epileptogenic zone. Discharges from other epileptogenic zones not directly activated by the tasks are increased, however. PMID- 2245805 TI - Topographic comparative study of magnetic resonance imaging and electroencephalography in 34 children with tuberous sclerosis. AB - A series of 34 children with confirmed tuberous sclerosis (TS) were studied prospectively by both EEG and magnetic resonance imaging (MRI) at ages ranging from 5 months to 18 years. Size and topography of the cortical tubers were analyzed on axial and coronal views, in T2 sequences, and the large tubers greater than 10 mm were studied. In addition, EEG follow-up data were reviewed retrospectively. Twenty-six patients (76%) had both MRI large cortical tubers and EEG foci, 3 had normal EEG, 2 had normal MRI, and the remaining 3 had only small tubers. The number of large tubers was significantly related to EEG foci. A topographic MRI/EEG correspondence was observed for at least one tuber in 25 of the 26 patients, and correspondence was complete in 10 patients. Large cortical tubers without corresponding EEG foci were observed in 11 patients; these tubers mainly involved the frontal regions and were found before the patients were 2 years old. EEG foci without corresponding tubers were observed in 4 patients. In addition, secondary bilateral synchrony was preferentially observed in patients with frontal lesions and after the age of 2 years. These data confirm that the cortical tubers are epileptogenic and that their expression may be influenced by regional cortical maturation. PMID- 2245806 TI - National Institutes of Health Consensus Development Conference Statement: Surgery for Epilepsy, March 19-21, 1990. PMID- 2245807 TI - Lack of substantial five year disease-free survival by primary aggressive surgery and cisplatin-based chemotherapy or by salvage intraperitoneal cisplatin-based chemotherapy. PMID- 2245808 TI - Application of thymic factor "Thymalin" in complex treatment of endometrial cancer patients. AB - Indications have been received of cell immunity in 111 primary endometrial cancer patients in the process of complex treatment: hormonotherapy+surgery. These indices have revealed correlation with pathogenetic variants of disease. Suppression has also been registered of T-lymphocytes under the influence of complex treatment. 35 patients received thymic factor "Thymalin" as a component of complex treatment. Its positive effects on cell immunity and some clinico morphological parameters have been registered. PMID- 2245809 TI - Recurrent ovarian granulosa cell tumor: role of combination chemotherapy with report of a long-term response to a cyclophosphamide, doxorubicin and cisplatin regimen. AB - We report a patient who, at age 43, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for an unrupted 10 cm granulosa cell tumor. A recurrence was subtotally totally resected 2.5 years later, followed by six cycles of cyclophosphamide, doxorubicin, and cis-platin (CAP) chemotherapy. She had no evidence of disease at second-look laparotomy. Serum estradiol (E2) levels paralleled her clinical course, becoming elevated at the time of her recurrence, and returning to postmenopausal levels during her chemotherapy. Four years later, further elevation in E2 heralded a second recurrence of tumor. The patient underwent a cytoreductive procedure and has resumed chemotherapy. Reports of the few other patients treated with multiagent chemotherapy are reviewed. Several combinations appear active, with the CAP regimen having possibly less toxicity. Compared with radiotherapy, chemotherapy may yield longer survival in patients with recurrent granulosa cell tumor, but actual cure remains elusive. PMID- 2245810 TI - Biochemical aspects of the hormonal therapy of endometrial adenocarcinoma. AB - This paper reports an investigation of the mechanism involved in the response of endometrial adenocarcinoma to MPA. The following protocol was used for a period of 8 years: 1 g/day MPA per os for 30 days and 60 days after surgery, following by 500 mg/day for 1 year. Adenocarcinoma glycolytic activity, G-6-P cycle, polyamine concentration, and the activity of ornithine decarboxylase (ODC), i.e. the first enzyme in polyamine synthesis, were compared before and after the 30/day treatment. The modifications induced by MPA are discussed and related to the pathological picture in an attempt to determine the characteristics of responding tumors. PMID- 2245811 TI - Immunoreactive and estrogen-binding estrogen receptors, and progestin receptor levels in uterine leiomyomata and their parental myometrium. AB - Estrogen receptor (ER) and progestin receptor (PR) levels in the myometria and uterine leiomyomata of forty-four women were studied. A radio-ligand method and an immuno-enzymatic method were used for ER measurement, and only a radio-ligand method was used for PR measurement. The leiomyomata contained significantly more PR and estrogen-binding ER than their parental myometria but not the immunoreactive ER per mg of DNA. Nuclear extracts from the myometria contained a high amount of the estrogen-nonbinding immunoreactive ER; in the leiomyomata, the bulk of this particular ER fraction was extracted with cytosol. Dissimilar distribution patterns of immunoreactive, estrogen-nonbinding ER in leiomyomata and normal myometria suggest that an impaired metabolism of ER may contribute to myoma growth. PMID- 2245812 TI - A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical carcinoma. AB - CA125 (reference value [RV] = 35 U/mL), CA50 (RV = 20 U/mL), CA72.4 (RV = 3.8 U/mL) and SCC (RV = 3.6 ng/mL) levels were retrospectively assayed in blood samples collected at diagnosis from 42 patients with endometrial carcinoma, 45 patients with cervical carcinoma and 68 patients with benign uterine pathology as controls. Among the patients with endometrial carcinoma. CA50 was the antigen with the highest sensitivity (SE) (34.4%) followed by CA125 (26.2%), CA72.4 (21.9%) and SCC (16.7%). The incidence of elevated serum CA125 and CA72.4 levels was significantly greater in advanced stages than in early ones (66.7% vs 19.4%, p = 0.032 for CA125; 66.7% vs 11.5%, p = 0.012 for CA72.4), while CA50 positivity was not significantly correlated with the extent of disease (50% in advanced stages vs 30.8% in early ones, p = 0.38). Among the patients with cervical carcinoma, CA125 and CA50 respectively showed a SE of 33.3% and of 42.9% for adenocarcinoma, while SCC had a SE of 33.3% and of 42.9% for squamous cell adenocarcinoma; in particular among the patients with squamous cell carcinoma, the incidence of elevated SCC levels was correlated with the extent of tumor (57.1% in advanced stages vs 12.5% in early ones, p = 0.013). In conclusion, CA50 and CA125 were the most sensitive tumor markers in both endometrial carcinoma and cervical adenocarcinoma, while SCC was the most reliable antigen for squamous cell carcinoma of the cervix. Because of the affinity of SCC, CA50 and CA125 for different histological types of cervical carcinoma, the combined evaluation of SCC with CA50 or CA125 showed an increased SE with respect to each marker alone. PMID- 2245813 TI - Secondary tumors of the ovary. III. Tumors of the gastrointestinal tract and other sites. AB - 16 cases of secondary ovarian tumors observed from 1977 to 1986, and in which the primary neoplasms involved other organs outside the genital tract or the breast, are studied. The observations concerned 13 metastases of the gastro-intestinal tract cancer (6 typical Krukenberg tumors, 3 "tubular" Krukenberg tumors, and 4 non-Krukenberg tumors), 1 urinary bladder cancer, 1 pancreatic cancer, and 1 tumor of unknown origin (probably an amelanotic melanoma). The histological diagnosis was very difficult in patients with no evidence of the primary malignancy, or in patients in whom the metastases simulate a concomitant primary ovarian tumor. The characteristic histological findings, histochemistry, and immuno histochemistry may suggest a correct diagnosis in most of situations. PMID- 2245814 TI - Beneficial effects of sucralphate in radiation induced diarrhea. An open randomized study in gynecological cancer patients. AB - In an open randomized study including 51 consecutive patients with gynaecological malignancies sucralphate was daily administered to patients receiving pelvic irradiation. Sucralphate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, seems to be of value in preventing radiation-induced bowel discomfort. The most objective parameter, frequency of diarrhoea was almost 50% less in the sucralphate groups as compared to the controls. The patients receiving sucralphate in general displayed only minor alterations in bowel habits even at the end of the radiation treatment. The number of patients requiring symptomatic therapy with loperamide were markedly lower in the sucralphate group. Subjective discomfort such as nausea, vomiting, loss of appetite were also less common. A reduction in acute reactions to irradiation increases the possibility of carrying through planned treatment and avoids unfavourable intermissions, and thus curing the patient with cancer in the pelvis by means of radiotherapy. PMID- 2245815 TI - Uterine cervix carcinoma diagnosed during puerperium. Case report. AB - The Authors describe a case of invasive uterine cervix squamous carcinoma in a 30 year old woman, diagnosed soon after delivery. They point out the rarity of the tumor during puerperium and illustrate its clinico-pathological aspects. PMID- 2245816 TI - The role of adjuvant chemotherapy in the treatment of uterine sarcoma patients. AB - 41 uterine sarcoma patients completed their post-operative adjuvant treatment at Istanbul University, Oncology Institute. Of these patients 23 had pelvic irradiation (RT group) and 18 had pelvic irradiation plus chemotherapy (RT + CT group). The 3 year survival rates of the two adjuvant treatment arms were 36% (RT group) and 66% (RT + CT group) (0.05 greater than p greater than 0.02). This difference is statistically significant. The 5 year survival rates were 18% (RT group) and 51% (RT + CT group) (0.1 greater than p greater than 0.05). Although the survival advantage at 5 years is not statistically significant because of the low number of patients, the use of adjuvant chemotherapy in uterine sarcomas seems to bring some survival benefit, probably by controlling subclinical distant disease. PMID- 2245817 TI - Corticosterone and ambulatory activity in the (ovariectomy and adrenalectomy) rats. AB - The present study was undertaken to investigate the importance of corticosterone (CORT) on the ambulatory activity in the ovariectomized (OVX) rats by employing the automatic apparatus for continuous and direct measurement of ambulation. A significant increase in ambulatory activity was observed in the OVX rats by treatment with estradiol benzoate (E2) (1 microgram/day) for 7 days. Higher dose of E2 (10 micrograms/day) showed a more potent effect on the ambulatory activity. On the other hand, E2 replacement had no effects on ambulatory activity in the OVX + adrenalectomized (ADX) rats. After administration of CORT + E2, ambulatory activity restored to the intact control level in the (OVX + ADX) rats. These data suggest that CORT may be indispensable on the E2-induced increase of ambulatory activity in the (OVX + ADX) rats. PMID- 2245818 TI - (6R)-5,6,7,8-tetrahydro-alpha-biopterin affects vasopressin and oxytocin release from rat neurointermediate lobe in vitro. AB - Incubation of neurointermediate lobes in Locke's solution containing 0.13 mumol.l 1 (6R)-5,6,7,8-tetrahydro-alpha-biopterin dihydrochloride (THB4) resulted in an inhibition of bioassayed vasopressin secretion and in an increase of that of oxytocin both under resting conditions as well as during depolarization due to excess potassium. It is suggested that some events related to THB4 and localized in the neural lobe are involved in the mechanism of vasopressin and oxytocin release. PMID- 2245819 TI - Bifemelane hydrochloride reduces plasma beta-endorphin-like immunoreactivity levels in rats. AB - The effect of bifemelane hydrochloride on plasma beta-endorphin-like immunoreactivity (beta-En-LI) levels in rats was studied. Bifemelane hydrochloride (25 mg/kg) was injected i.p., and the animals were decapitated at various times after the administration. The plasma beta-En-LI levels were measured by radioimmunoassay. The effect of bifemelane hydrochloride on beta-En LI release from the anterior pituitary was also investigated by means of an in vitro experiment. The beta-En-LI content in the hypothalamus and pituitary gland did not change significantly after bifemelane hydrochloride injection. The plasma beta-En-LI levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. The beta-En-LI release in vitro from the anterior pituitary was inhibited with the addition of bifemelane hydrochloride. The findings suggest that bifemelane hydrochloride acts on the anterior pituitary to inhibit beta-En-LI release. PMID- 2245820 TI - Changes in beta-endorphin-like-immunoreactivity in the blood plasma of ewes during estrous cycle and in anestrous ewes under stress condition. AB - In the light of evidence for endogenous opioid peptide involvement in the modulation of pituitary hormone release and in the body's overall response to stress, the aim of the present study was to determine the beta-endorphin-like immunoreactivity (beta-END-LI) in the blood plasma of ewes during different phases of the estrous cycle and in anestrous ewes subjected to acute or intermittent prolonged footshocks. The highest concentration of beta-END-LI was found in the blood plasma during the luteal phase and lowest one during the follicular stage at proestrus. Nearly equal concentrations of beta-END-LI were determined at estrus and metestrus; their values were over 10 times lower than those observed in the luteal phase. Acute stress caused transient increase of beta-END-LI in the blood plasma of anestrous ewes, with a peak after 15-30 min of footshock application and changes in the molar ratio of beta-LPH to beta endorphin. No apparent increase in mean daily levels of beta-END-LI was noted in ewes subjected to prolonged footshocking; however, on the day after stimulation beta-END-LI concentration decreased below control values. These results indicate that: 1. secretion of beta-END-LI varies during different phases of the estrous cycle, 2. acute stress is a potent activator for beta-END-LI secretion, 3. no apparent increase of beta-END-LI in the blood plasma of ewes subjected to prolonged stress concomitant with accumulation of this material in pituitary (Polkowska and Przekop, 1988) supports the idea, that prolonged stress augments the synthesis of beta-END-LI but not its release. PMID- 2245821 TI - Serum aldosterone response to metoclopramide in normal subjects and acromegalic patients. AB - The acute effects of metoclopramide on aldosterone and prolactin levels were studied in 11 normal subjects, 8 normotensive and 8 hypertensive acromegalics. Metoclopramide (10 mg i.v.) induced a similar serum aldosterone increase in normal subjects and normotensive acromegalics. Hypertensive acromegalics showed elevated basal serum aldosterone level and blunted aldosterone response to metoclopramide. The prolactin response to metoclopramide was blunted in acromegalics in comparison with normal subjects but the difference was statistically significant only in hypertensive patients. The blunted aldosterone and prolactin responses to metoclopramide in hypertensive acromegalics suggest that there is a dopamine deficiency at central and adrenal level in these patients. PMID- 2245822 TI - Decreased peripheral insulin sensitivity in acromegalic patients. AB - In 13 nondiabetic acromegalic patients glucose homeostasis was studied by use of the hyperglycaemic clamp technique and compared to a group of sex and age matched and a group of sex, age and weight matched controls. When compared to a control group of normal weight glucose stimulated insulin release (I) was significantly increased and tissue sensitivity to insulin (M/I) significantly decreased. However, no significant differences were observed when the parameters were compared with a weight matched group. Glucose stimulated insulin release correlated positively with growth hormone (GH) and somatomedin-C levels, whereas no such a correlation could be obtained for M/I. Thus, chronic growth hormone excess seems to induce hyperinsulinaemia which in turn leads to obesity and metabolic changes comparable to those of obesity. PMID- 2245823 TI - Circulating levels of placental protein 10 (PP 10) in diabetic pregnancy complicated by retinopathy. AB - Placental protein 10 (PP 10) is a soluble tissue antigen of the placenta. PP 10, a glycoprotein, was tested in diabetic pregnancy complicated by retinopathy. A continuous increase in PP 10 serum levels until weeks 35-36 is followed by a fall thereafter up to term. The mean of the healthy control group between 32 and 39 weeks gestation was 22 +/- 10 micrograms/l. In diabetic pregnancies complicated by retinopathy there were measured 69 +/- 24 micrograms/l in benign form and 77 +/- 26 micrograms/l in proliferative form. Both of these values are significantly (p less than 0.05) above the control values. Increased PP 10 levels in diabetic pregnancy complicated by retinopathy are probably caused by placental and amniotic leakages. PMID- 2245824 TI - Simultaneous occurrence of diabetes insipidus and ascites due to liver cirrhosis: clinical and pathophysiological studies. AB - Authors describe the simultaneous occurrence of ascites due to liver cirrhosis and diabetes insipidus in a patient with consistently normal urine volume. The diagnosis of diabetes insipidus has been proved by the water deprivation test combined with the administration of dDAVP as well as by serial determinations of plasma arginine vasopressin levels before and during infusion of hypertonic sodium chloride solution. Authors discuss the differential-diagnostic difficulties of the case and consider the mechanisms playing a role in the abolishment of diabetic polyuria by hepatic disease. PMID- 2245825 TI - Occurrence of antithyroxine antibodies in rabbits immunized with iodine-poor human thyroglobulin. AB - Thyroglobulin (Tg) is a large glycoprotein with polymorphic structure and its heterogeneity has been demonstrated by many investigators. In order to obtain appropriate antibodies against human Tg which appear in the circulation of patients with thyroid carcinoma, a number of rabbits (19) were immunized with poorly iodinated h-Tg (0.05%). During the period of immunization the level of T3 and T4 was followed in sera, as well as the titre of anti-h-Tg antibodies. The production of antibodies against h-Tg was observed in all immunized rabbits (8, 13, 16, and 54 weeks from the first immunization). Titres of anti-h-Tg antibodies in sera at the 16 and 54-week bleeding were very high (Ka = 2.0 X 10(10) M-1). A few immunized rabbits were found to have a very low concentration of serum T4 (determined by RIA-PEG method). Sera from these animals contained antibodies against T4, but not against T3. Their identification and characterization was performed by a radioimmunological method. In summary, our results show that after immunization of rabbits with low-iodinated, i.e. hormone-poor human Tg, antibodies against thyroxine can be produced. However, occurrence of anti thyroxine antibodies in some immunized rabbits indicates that the immunogenicity of hormone residues in poorly iodinated h-Tg is much lower than in normal iodinated molecule. PMID- 2245826 TI - Comparison of endometrial biopsy and urinary pregnanediol glucuronide concentration in the diagnosis of luteal phase defect. AB - To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained. PMID- 2245827 TI - Evaluation of the stimulated menstrual cycle by magnetic resonance imaging. AB - Changes in uterine zonal anatomy in six women during a cycle of treatment with clomiphene citrate is studied by magnetic resonance imaging. There was a rapid rate of increase in endometrial thickness during the periovulatory period that was similar to the pattern seen in a prior study of women with normal (nonstimulated) cycles. Junctional zone thickness did not parallel the endometrial pattern and differed from the response seen in nonstimulated cycles. Results of large scale studies may help to further understand the effects of these medications. PMID- 2245828 TI - Late luteal administration of the antiprogesterone RU486 in normal women: effects on the menstrual cycle events and fertility control in a long-term study. AB - Twelve regularly cycling women, with contraindications to other methods of contraception, received RU486 (Roussel UCLAF, Romainville, France), once a month as a method of fertility control. The study was designed for 18 consecutive cycles. Each patient recorded basal body temperature, detected urinary luteinizing hormone peak, and collected saliva samples during each luteal phase for progesterone (P) determinations. A single dose of RU486, 600 mg, was given on the day before the expected date of the menses and 8 days later in case of continuing pregnancy after the first dose. Blood samples were collected for estradiol, P, and beta-human chorionic gonadotropin analyses on these two occasions. The compliance was poor and the results of only 137 cycles were obtained. The menstrual cyclicity was not significantly modified during this long term study. Of the 137 cycles, 22 pregnancies occurred (16%), and 4 (18.2%) were not interrupted by the second dose of RU486. Thus, because of the high failure rate, use of RU486 at the time of the natural P withdrawal cannot be advocated as a "once-a-month" contragestive agent. PMID- 2245829 TI - Plasminogen activators, plasminogen activator inhibitor, and fibronectin in human granulosa cells and follicular fluid related to oocyte maturation and intrafollicular gonadotropin levels. AB - We determined the relative distribution of tissue plasminogen activator (TPA) antigen, urokinase-type PA antigen, PA inhibitor activity, and fibronectin levels in lysates of human granulosa cells (GC) and the respective follicular fluid (FF) in relationship to oocyte-corona-cumulus complex morphology. In addition, FF gonadotropins were measured to investigate a possible relationship of gonadotropins to PA activity. A significant increase of TPA antigen in GC lysates of intermediate and mature oocyte-corona-cumulus complex was found when compared with immature oocyte-corona-cumulus complex. Urokinase-type plasminogen activator levels and PA inhibitor levels did not reveal any significant differences between the different groups. In FF the concentrations of PA and PA inhibitor were significantly lower than in GC lysates and showed no significant difference between the oocyte-corona-cumulus complex groups. The concentration of fibronectin was significantly elevated in GC lysates of mature follicles. The marked increase of TPA in human GC during oocyte maturation showed a positive correlation with the increase of FF follicle-stimulating hormone and beta-human chorionic gonadotropin in the group of mature oocyte-corona-cumulus complex. The data obtained suggest that in man TPA is the predominant PA involved in the process leading to follicular rupture. PMID- 2245830 TI - Effect of insulin-like growth factor I on deoxyribonucleic acid synthesis in cultured human granulosa cells. AB - Insulin-like growth factor I (IGF-I) has been proposed to be an autocrine/paracrine factor involved in granulosa cell proliferation and differentiation. The present study focuses on a possible mitogenic effect of IGF I in human granulosa cells. Insulin-like growth factor I (1 to 10 ng/mL) significantly stimulated 3H-thymidine incorporation in granulosa cells obtained from both natural cycles and from patients stimulated for in vitro fertilization, whereas luteinizing hormone (LH, 10 ng/mL), follicle-stimulating hormone (FSH, 10 ng/mL) and epidermal growth factor (EGF, 10 ng/mL) had no apparent effect on deoxyribonucleic acid (DNA) synthesis under these conditions. Luteinizing hormone and FSH stimulated progesterone secretion whereas IGF-I and EGF were without effect. Our observations that IGF-I stimulates DNA synthesis in human granulosa cells is in agreement with previous reports, in other species, indicating that IGF-I might be of importance for granulosa cell proliferation. PMID- 2245831 TI - The placebo response of subfertile couples to attending a tertiary referral centre. AB - The objective of this study was to determine whether there was a placebo response to clinic attendance in couples with prolonged (greater than 4 years) subfertility. From 4 to 18 years of subfertility we observed a treatment independent cumulative conception rate of 22%, which was independent of the length of subfertility. Twenty-seven women conceived after 1 to 4 years' subfertility, and 30 conceived after greater than 4 years' subfertility. The fecundity of the latter group was significantly greater than that of women with 1 to 4 years' subfertility, being similar to "normal" subjects who had stopped contraception. This study demonstrates that a subgroup of apparently normal women with greater than 4 years' subfertility responded positively to clinic attendance independent of any investigation(s) or therapy. PMID- 2245832 TI - Home monitoring of gonadotropin ovulation induction using the Ovarian Monitor. AB - The safe use of gonadotropins relies on close hormonal and/or ultrasound monitoring to assess the response to treatment, requiring multiple hospital visits. Home monitoring with the Ovarian Monitor (St. Michael Research Foundation, Macleod, Victoria, Australia) minimizes hospital visits and overcomes many of the logistic difficulties associated with gonadotropin use. It utilizes a system of homogenous enzyme immunoassay using lysozyme conjugates to measure quantitatively either urinary estrone-3 or pregnanediol-3-glucuronide. Results obtained by 24 patients in 57 cycles using the Ovarian Monitor at home correlate closely with results obtained in the laboratory (estrone-3-glucuronide r = 0.955; pregnanediol-3-glucuronide r = 0.958). Cycle outcomes (ovulation, 74%/cycle; clinical pregnancy, 30%/cycle; multiple pregnancy, 13%/pregnancy; hyperstimulation, 11%/cycle) are no different from those achieved in laboratory monitored patients. Home monitoring can be as safe and effective as laboratory monitoring, offers significant social benefits, and improves access to this form of therapy. PMID- 2245833 TI - A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. AB - This study was initiated to test the hypothesis that treatment with clomiphene citrate (CC) and intrauterine insemination (IUI) results in increased fecundity when compared with periovulatory intercourse in couples with either unexplained infertility or surgically corrected endometriosis. Sixty-seven couples entered a randomized, prospective trial comparing CC/IUI with observation. During the study, there were 14 pregnancies in 148 treated cycles (fecundity = 0.095) compared with 5 pregnancies in 150 untreated cycles (fecundity = 0.033). Using life-table analysis and the log-rank test, the difference in fecundities was statistically significant. Pregnancy outcome was not significantly different between the two groups. When comparing conception with nonconception cycles during treatment, no differences between the size of the lead follicle or the number of dominant follicles was detected. We conclude that treatment with CC/IUI improves fecundity in couples with unexplained infertility or surgically corrected endometriosis. PMID- 2245834 TI - Pregnancy rates after double versus single insemination with frozen donor semen. AB - Ninety-nine females (mean age 34 years +/- 1) were seen for therapeutic donor insemination using frozen semen. All patients used over-the-counter urinary ovulation predictor kits, with the insemination scheduled either the day after the positive test (group I; n = 46) or consecutively the day of and the day after the positive test (group II; n = 53). Group I patients underwent a total of 113 cycles of insemination (mean 2.5 cycles/patient). Seven pregnancies were achieved in group I for an overall success of 15.2% and a monthly fecundability of 0.06. Group II patients underwent a total of 100 cycles of therapeutic donor insemination (mean of 1.9 cycles/patient). Twenty-one pregnancies were achieved in this group for an overall success rate of 39.6% and fecundability of 0.21. The estimated cumulative probability of conception (F) for 6 months was 0.32 in group I and 0.78 in group II. These data indicate that the F after therapeutic donor insemination with frozen semen is greater if two consecutive inseminations are performed at midcycle. PMID- 2245835 TI - Cryopreserved/thawed semen for in vitro fertilization: results from fertile donors and infertile patients. AB - We evaluated the in vitro fertilization (IVF) outcome in 54 cycles using cryopreserved/thawed semen from fertile donors. Controls were other IVF patients matched by time frame, female age, stimulation protocol, number of pre-embryos transferred, and absence of a male factor using freshly ejaculated normal semen samples. In the study group and controls, respectively, post-thaw swim-up motility was 83.1% and 89.5%; fertilization rate of preovulatory oocytes (91.8%, 95.7%) and ongoing pregnancy rate (PR) per transfer (21.1%, 25.0%) were similar. The excellent fertilization rate with frozen/thawed semen was achieved through high-concentration insemination (0.5 x 10(6) motile sperm/mL). With use of frozen/thawed samples from infertile men (normal and subfertile samples), PR was similar but fertilization rate was lower. Cryopreserved semen is a valuable option for infertile couples in IVF therapy. PMID- 2245836 TI - Fertility prognosis for infertile men: results of follow-up study of semen analysis in infertile men from two different populations evaluated by the Cox regression model. AB - Using the Cox proportional hazard regression model on one material (group I = 765, 1950 to 1951) we have identified four variables of semen analysis with significant prognostic information about fertility. The four variables were combined into a model for establishing the probability of the individual male to achieve pregnancy as a function of time. This model is tested first on another material (group II = 321, 1977 to 1985). A Goodness-of-fit test indicates excellent agreement between the expectations from the model and the observed number of pregnancies in group II. Second, the two groups are pooled (= 1,086). Then only three variables give significant prognostic information about the time until pregnancy: (1) the man's age at semen analysis (years); (2) the percentage of morphologically normal spermatozoa (ln %); and (3) the degree of motility (good/poor). These three important variables enter into a new and better prognostic model. PMID- 2245837 TI - Correlation between quantitative antibody titers of sperm immobilizing antibodies and pregnancy rates by treatments. AB - Immunological infertility in women who possessed sperm immobilizing (SI) antibodies made it very difficult to conceive using the usual treatments. We examined SI antibodies by the quantitative Sperm Immobilization Test and found the antibody titers (50% sperm immobilization unit: SI50 unit) associated with pregnancy rates. Patients with high SI50 titers (greater than 10 units) did not conceive by ordinary or repeated artificial inseminations with husband's semen (AIH) except when treated with in vitro fertilization (IVF) and embryo replacement. Patients with relatively low SI50 titers (less than 10 units) could conceive either by repeated or ordinary AIH, though the success rates were lower than by IVF-embryo replacement. It is important to assess the SI50 titers by the quantitative method to select treatments for infertile women with SI antibodies. In follow-up studies of the patients who conceived successfully, it was found that SI50 titers tended to decline as pregnancy proceeded. PMID- 2245838 TI - Changes in sperm antibody test results when spermatozoa are subjected to capacitating conditions. AB - Cytotoxic and immunobead-binding antibody assays were used to document possible changes in antigenicity after the spermatozoa were subjected in vitro to capacitating conditions. Serum and seminal plasma immunobead-binding immunoglobulin (Ig)A, sperm surface IgG, and IgA, and seminal plasma cytotoxic antibody titers in 26 autoimmune infertile men were decreased against autologous spermatozoa under capacitating conditions. Cytotoxic antibodies and immunobead binding IgG, IgA, and IgM against husbands' sperm undergoing capacitation, in the cervical mucus of these women, were less than those against uncapacitated sperm. Conversely, sperm antibody levels were increased against the capacitated husbands' sperm in the husbands' serum and wives' cervical mucus, originally testing negative for cytotoxic antibodies against uncapacitated sperm. Antibody levels were unaltered against donors' sperm undergoing capacitation, except for a reduction in titers in the serum of isoimmune wives. The differences in sperm antibody assay results, depending on whether or not spermatozoa are incubated under conditions favoring capacitation, are specific to the husbands' and not to the donors' spermatozoal antigens. PMID- 2245839 TI - Effect of follicular fluid on sperm movement characteristics. AB - Human spermatozoa previously washed from seminal plasma and incubated in capacitating medium were exposed to human follicular fluid (FF) for different time periods and their movement characteristics were examined by computer assisted digital image analysis. No differences from control samples were observed after short exposures (15 minutes and 2 hours). When the exposure was prolonged to 6 hours, spermatozoa incubated in the presence of FF displayed significant differences in some movement characteristics as compared with samples incubated without FF supplement. When only rapidly moving sperm subpopulations were considered, these effects of FF were similar to those produced by a short incubation with the solubilized cumulus oophorus matrix as described previously. After 24 hours of incubation, there was a remarkable beneficial effect of FF on motility preservation. Possible physiological and clinical implications are discussed. PMID- 2245840 TI - A novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH: controlled restoration of gonadotropin secretion and ovulation induction. AB - Using a primate model, we have tested a novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH for the achievement of controlled restoration of gonadotropin secretion and ovulation induction. As a prelude, ovariectomized cynomolgus monkeys (n = 3) were treated with Antide ([N-Ac-D Nal(2)1, D-pCl-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6, Lys(iPr)8, D-Ala10]-GnRH) (3 mg/kg per day) for 6 consecutive days. On the 7th day, pulsatile GnRH therapy was initiated in a 7 day-on: 7 day-off regimen for a total of four exposures. Next, four intact monkeys were given Antide to suppress ovarian function (estradiol less than 10 pg/mL) followed by pulsatile GnRH. In the ovariectomized monkeys, Antide-induced suppression of gonadotropin concentrations was reversed by the pulsatile GnRH so that follicle-stimulating hormone concentrations were completely normalized and luteinizing hormone concentrations were returned to within the lower range (+/- 2 SD) of the pretreatment mean. The abruptness of the onset or loss of gonadotropin secretion was precisely synchronized with the weekly on and off phases of the GnRH pulse regimen. In intact monkeys, ovarian steroid secretions were abruptly subdued and then successfully re-established by pulsatile GnRH in the face of sustained circulating levels of Antide. Thus, we conclude that our primate model of combination therapy, GnRH antagonist plus pulsatile GnRH, establishes the possibility of a new clinical treatment regimen for patients desiring relief from the sequelae of hyperandrogenemia (polycystic ovarian disease) and ovulatory dysfunction. PMID- 2245841 TI - Effect of 20 alpha-dihydroxyprogesterone on the estrogen-induced bioactive luteinizing hormone surge in ovariectomized monkeys. AB - Progestins facilitate estrogen induction of the preovulatory luteinizing hormone (LH) surge. A biologically weaker progestin, 20 alpha-dihydroxyprogesterone, is reportedly increased at midcycle, but the importance of 20 alpha dihydroxyprogesterone in regulating LH release has not been systematically studied. We therefore evaluated the effect of 2 doses of 20 alpha dihydroxyprogesterone on the bioactive LH surge onset in ovariectomized monkeys. Chronically cannulated monkeys (n = 10) received estradiol (E2) benzoate (50 micrograms/kg) with and without subsequent 20 alpha-dihydroxyprogesterone injections (50 micrograms/kg, n = 3 and 100 micrograms/kg, n = 3). Blood was collected every 15 minutes over preselected intervals and the plasma assayed for bioactive LH and gonadal steroids. Low-dose 20 alpha-dihydroxyprogesterone administration resulted in periovulatory peripheral 20 alpha dihydroxyprogesterone levels and did not advance the bioactive LH surge onset. In contrast, high-dose 20 alpha-dihydroxyprogesterone resulted in supraphysiological 20 alpha-dihydroxyprogesterone levels, slight increases in progesterone levels, and significant advancement of the surge over E2 benzoate treatment alone. We conclude that periovulatory levels of 20 alpha-dihydroxyprogesterone do not play a role in modulating the estrogen-induced bioactive LH surge. PMID- 2245842 TI - Elevated luteal phase estradiol:progesterone ratio in mice causes implantation failure by creating a uterine environment that suppresses embryonic metabolism. AB - Failure of implantation after in vitro fertilization is sometimes associated with elevated estradiol (E2):progesterone (P) ratios in the early luteal phase. Using the mouse to study the causes of the contragestational actions of elevated E2:P ratios, it was confirmed that administration of E2 (40 to 80 ng) before implantation inhibited implantation and 0.4 mg of P totally reversed the effect of 40 ng E2. Fluids collected from the uterine lumen of E2-treated (40 ng) mice significantly inhibited the incorporation of 3H-uridine by mouse blastocysts in vitro, whereas fluids from mice treated with E2 (40 ng) and P (0.4 mg) together had no inhibitory effect. In contrast to these contraceptive effects of high E2, lower levels of E2 (5 and 20 ng) caused an increase and no change to the implantation rate, respectively, and fluids from mice treated with E2 (20 ng) significantly enhanced blastocyst metabolism. Concomitant administration of P to these low dose E2 mice enhanced these effects. Thus, a large elevation of the E2:P ratio inhibited implantation and created a uterine lumenal milieu that suppressed embryonic metabolism. These effects could be reversed and implantation re-established by the correction of the E2:P ratio by exogenous P. PMID- 2245843 TI - Analysis of immunosuppressive molecules associated with murine in vitro fertilized embryos. AB - Supernatants from mouse in vitro fertilized (IVF) oocyte cultures may suppress in vitro lymphocyte proliferation stimulated by concanavalin A (Sigma, St. Louis, MO). Supernatants conditioned by incubation with mouse epididymal sperm alone were even more inhibitory. Thin-layer chromatography suggested the polyamines spermine in sperm and spermine plus spermidine in IVF embryo supernatants were responsible. Putrescine was not suppressive. In vitro fertilized oocytes from old CBA/J-strain mice (greater than 20 weeks) that suffer age onset infertility lacked suppression and manifest cleavage arrest that could be partially reversed by adding spermine to the cultures. The failure of IVF oocytes to produce adequate quantities of polyamines could lead to failure of implantation due to division arrest. A possible in vivo role of polyamines as immunosuppressor factors is discussed. PMID- 2245844 TI - Effect of a specific estrogen antibody on pregnancy establishment in the bonnet monkey (Macaca radiata). AB - The requirement for estrogen for pregnancy establishment has not been conclusively demonstrated in primates. Selective neutralization of estrogens was achieved in mated female monkeys during preimplantation and postimplantation periods by injecting characterized estrogen antiserum from either day 14 to 18 or day 28 to 32 of cycle. While estrogen deprivation during preimplantation period in 5 animals exposed to 14 ovulatory cycles resulted in only one pregnancy, only 3 of 13 monkeys treated during postimplantation period continued pregnancy to term. In comparison with controls (4 of 5 monkeys becoming pregnant), the percent protection against pregnancy in animals treated during preimplantation period was 93. The pregnancy termination in 10 of 13 monkeys treated during postimplantation period when compared with normal postimplantation pregnancy wastage in our colony (2%) is also highly significant (P less than 0.01). The present study demonstrates a critical need for estrogen during the peri-implantation period for a successful pregnancy establishment in primates. PMID- 2245845 TI - Twin pregnancy after diagnosis and treatment of ectopic implantation by retrograde selective salpingography and intraluminal methotrexate injection. AB - In this case report, a patient with a right tubal pregnancy was managed by a new procedure combining retrograde salpingography and local MTX injection. A twin pregnancy occurred shortly after treatment. We conclude that retrograde tubal cannulation may provide an alternative method for the diagnosis and treatment of selected EPs. PMID- 2245846 TI - Continuation of a donor oocyte pregnancy in menopause without early pregnancy support. AB - A case of successful impregnation of a functionally agonadal 45-year-old woman with donor eggs is reported. The placental takeover period was attained with no early exogenous E2 and P support. This case report highlights the need for further research on the ovarian function at menopause and the steroid hormonal requirements of early gestation. PMID- 2245847 TI - Establishment of pregnancies in humans after transcervical transfer of gametes immediately after oocyte retrieval. AB - This study, like that of Veersema et al. demonstrates the feasibility of direct intrauterine transfer of gametes in initiating pregnancy. Whether the success of this procedure can be further improved with modification (preincubation, in vitro insemination) remains the subject of continued investigation. Notwithstanding this uncertainty, we feel that transcervical transfer of gametes may be an alternative to IVF for patients with ethical concerns regarding IVF. PMID- 2245848 TI - Evidence that human follicular fluid contains a chemoattractant for spermatozoa. AB - Considering that information from the literature clearly establishes that human follicular fluid enhances both motility and viability of spermatozoa and that this fluid contains substances with chemotactic activity for leukocytes, we looked to see if follicular fluid might exert any chemical attraction to male germinal cells. In an vitro model using 0.8% agarose plates, it was demonstrated that the number of cells migrating to wells containing follicular fluids from patients in a program for GIFT, classified as mature in accordance to oocyte morphology, was significantly higher than those migrating to control wells. Further studies are needed to confirm these results and to study the possible specificity of the signal. PMID- 2245849 TI - Behavioral treatment for infertile women. PMID- 2245850 TI - Factors affecting scrotal temperature in monkeys. PMID- 2245851 TI - Neurological symptoms related to gonadotropin-releasing hormone agonist, low estrogen, or? PMID- 2245852 TI - Is bloody fluid endometriosis? PMID- 2245853 TI - Hypertrophy of technology. PMID- 2245854 TI - In defense of a function for the human epididymis. AB - In view of reports that the human epididymis may play no role in human fertility, literature on the fertilizing capacity of epididymal spermatozoa was reviewed. The survey indicates that under the circumstances of their retrieval, human epididymal and testicular spermatozoa may have the ability to fertilize human eggs both in vivo and in vitro. Although the "fertility profile" of the normal epididymis cannot be explored in man, a fair assumption would be that fertilizing capacity develops fully in the distal part of the tract, judging from the higher motility and egg fusing ability of sperm taken from these regions of unobstructed tissue. Motility and fertilizing capacity observed with IVF or artificial insemination, in which sperm are obtained from obstructed ducts, may occur at a level in the tract more proximal than normal, as in animals. The pregnancies resulting from aspiration of spermatozoa from, or anastomosis of the vas deferens to, the efferent ducts are of great clinical interest, but the pathological state of the tissue precludes definitive statements about the functioning of a normal epididymis. In the former case, the immediate origin of the fertilizing spermatozoon and the nature of the secretions previously bathing it are unknown and in the latter case the time needed before pregnancies occur is much greater than anticipated had fertile sperm been present in the proximal epididymis. The evidence supports neither the view that testicular sperm are inherently fertile nor that a simple aging of sperm cells is sufficient for the fertilizing potential of spermatozoa to be realized. It emphasizes, rather, the importance of the environment to which the sperm cells are subjected. Under abnormal conditions other accessory glands may secrete compounds that are necessary for the maturation of spermatozoa. Before more information is known of the exact situation existing, or having existed, in pathological human tissues from which fertilizing human spermatozoa can be obtained, great caution should be exercised in interpreting the results of pregnancies arising from the in vivo and in vitro insemination of testicular or epididymal spermatozoa. PMID- 2245855 TI - Close enough for highway work. PMID- 2245856 TI - The prevalence of subfertility: a review of the current confusion and a report of two new studies. AB - The difficulties inherent in measuring the prevalence of subfertility are discussed. Four subtypes of subfertility are defined, enabling comparisons to be made between the widely different approaches previously reported. A detailed assessment was made of the prevalence of subfertility in two different samples of British women aged 25 to 44 years, using interviews, postal questionnaires, and medical record searches. Data were collected on 872 women from a general practice and 702 hospital patients. The combined data showed that 24% of all women attempting to conceive experience an episode of subfertility at some stage in their reproductive life. Thirteen percent experience this in attempting to conceive their first child, and 17% when attempting to conceive a subsequent child. Three percent of women are involuntarily childless and 6% of parous women are not able to have as many children as they would wish. PMID- 2245857 TI - Neosalpingostomy for distal tubal obstruction: prognostic factors and impact of surgical technique. AB - We reviewed the clinical records of all women who underwent microsurgical terminal neosalpingostomy for distal tubal obstruction between January 1983 and June 1988. We identified 95 women whose preoperative evaluation revealed no other contributory factors for infertility and analyzed their pregnancy outcome after this procedure. Pregnancy success was inversely related to the extent of tubal distortion (dilation, rugal integrity, and status of the fimbria) and degree of adnexal adhesions. Using our classification system for distal tubal obstruction, patients with mild disease had an 80% pregnancy rate, whereas patients with moderate and severe disease had a 31% and 16% success rate, respectively. We found no statistically significant difference in pregnancy outcome when we compared this series with our previous group, reported in 1978, where contemporary microsurgical technique was not used. Although we feel that optimal surgical technique is important to maximize success, we conclude that the most important prognostic factor in pregnancy outcome after neosalpingostomy for distal tubal disease is the anatomical and functional integrity of the tube. PMID- 2245858 TI - Repair of the uterine cavity after hysteroscopic septal incision. AB - We performed a follow-up hysteroscopy with multiple biopsies at different intervals after surgery in 19 women who underwent hysteroscopic septal incision. Seven days after operation the sectioned areas were very evident and not epithelialized (3 patients). At 14 days, the incised zone was depressed with scattered epithelialization (5 subjects). At 1 month, the sectioned surfaces were still depressed and uniformly covered by thin endometrium (5 cases). After 2 months the uterine cavity was almost normal with minimal tendency to central fundal adhesions (6 women). Thus, spontaneous healing processes after hysteroscopic metroplasty progressed regularly and completely and there is probably no reason to delay attempts at pregnancy for longer than two cycles after surgery. PMID- 2245859 TI - Ultrasound-guided transcervical metroplasty. AB - A new technique of metroplasty is described. The septum is divided with 4-mm endoscopic scissors introduced into the uterine cavity through the cervix. The whole procedure is monitored by a real-time ultrasound scanner. Twenty-four patients were operated on with this technique. No complication was encountered. Fifteen patients had third trimester deliveries or ongoing pregnancies. Among 12 patients who had suffered repetitive pregnancy losses, 11 desired pregnancy: 10 have been successfully pregnant beyond the second trimester (91.7%), 8 are delivered, and the living birth rate is 72.7%. These results equal those obtained after hysteroscopic metroplasty. The procedure is short, safe, requires no special equipment, and does not necessitate concomitant laparoscopy. PMID- 2245860 TI - Neodymium: YAG laser hysteroscopy in large submucous fibroids. AB - The preoperative use of a potent, subcutaneously injected gonadotropin-releasing hormone agonist (GnRH-a) was evaluated in a series of 60 women with large submucosal fibroids. Myomectomy by hysteroscopy and Nd:YAG laser was easily performed. In 12 cases, the largest portion of the myoma was not inside the uterine cavity and myomectomy was carried by a two-step hysteroscopy. In women who wished to become pregnant, a pregnancy rate of 66% was achieved. Advantages of preoperative use of a GnRH-a are (1) the significant decrease of the fibroid size, (2) a lower fluid absorption, and (3) the restoration of a normal hemoglobin concentration. PMID- 2245861 TI - Echocardiography update: when to order which test. AB - Echocardiography is a highly useful diagnostic technique providing clinical information concerning cardiac anatomy, function, and hemodynamics at low patient cost and risk. Its various modalities of M-mode, 2-D, Doppler and Color Flow combine in complementary fashion to provide the physician with information important in the diagnosis, therapy, and prognosis of a wide range of cardiovascular disorders. The addition of the transesophageal approach has expanded our ability to obtain more detailed information in patients whose hearts were previously inaccessible from the transthoracic approach or who have prosthetic devices with acoustic shadows which obscure important echocardiographic information. An understanding of the wide array of applications of echocardiography is important in making the best use of this valuable diagnostic tool. PMID- 2245862 TI - Update: breast cancer detection. PMID- 2245863 TI - Chromosomes, oncogenes, and neoplasia. PMID- 2245865 TI - Causes and effects. PMID- 2245864 TI - Breast cancer mortality in Delaware. 1986 preliminary analysis. PMID- 2245866 TI - Advertising and health care dollars. PMID- 2245867 TI - [Training and professional profile of dentistry in the EEC. 6]. PMID- 2245868 TI - [Planning a dental office. Motivation for remodeling]. PMID- 2245869 TI - [Diagnostic methods of pulp vitality. 1]. PMID- 2245870 TI - [Alloy telescopic crowns. Clinical indications]. AB - This work involves a partially edentate subject fitted with a denture on conical crowns. Of the methods at present used in patients with few teeth, this is considered one of the most satisfactory for dentist and patient. In cases in which the remaining teeth are moveable, a denture on magnets can be utilized. A correct oral hygiene is emphasized to favour the duration of the tooth-denture combination. PMID- 2245871 TI - [Fixed prosthetic reconstruction. Restoration of upper incisors. 3]. AB - Aware of having tackled a difficult topic in the present paper and also of the fact that all gnathological philosophies are open to sundry criticisms, we believe we have made a valid contribution with experimental, clinical and practical consequences in the functional reconstruction of the incisor guide. In addition, the clinical experimentation undertaken, even with the limitations resulting from the small number of patients examined, will allow us to study the group of patients at risk for the appearance of ATM pathologies over a period of twelve years. PMID- 2245872 TI - [Tempered composite resins in Ellis Class II fractures]. AB - The Authors present a new method to improve the characteristics of the sandwich technique for the treatment of Ellis second class fracture. PMID- 2245873 TI - Elusive proximal signals of beta-cells for insulin secretion. AB - The beta-cell is unique because its major agonists, i.e., insulin secretagogues, undergo metabolism instead of interacting with a receptor. This perspectives presents the hypothesis that the first part of a metabolic signal of a secretagogue is specific to the secretagogue and the beta-cell and can be envisioned as proximal. The second part, which occurs after transduction to more universal signaling mechanisms, is viewed as distal. Distal signaling and exocytosis in the beta-cell operate the same as in other cells. Aerobic glycolysis is required for glucose-induced insulin release. Because glyceraldehyde, which enters metabolism at the triose phosphates in the glycolytic pathway, is a potent insulin secretagogue but pyruvate, which is metabolized in the mitochondrion, is not an insulin secretagogue, the proximal signal for glucose-induced insulin release originates with an interaction between the central part of the glycolytic pathway and mitochondrial metabolism. The proximal message in leucine-induced insulin release originates with leucine allosterically activating glutamate dehydrogenase, which activates endogenous glutamate metabolism, and by the metabolism of leucine itself. The methyl ester of succinate is a potent experimental insulin secretagogue. It is puzzling why the glucose signal requires the interplay of glycolysis and mitochondrial metabolism, whereas the signals from leucine and succinate originate entirely from within the mitochondrion. Leucine-induced insulin release is suppressed and glucose-induced insulin release is activated in islets cultured at a high concentration of glucose. Conversely, leucine-induced insulin release is activated and glucose-induced insulin release is suppressed in islets cultured at low glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245874 TI - Insulin-mimicking anti-idiotypic antibodies in development of spontaneous autoimmune diabetes in BB/E rats. AB - BB/E rats spontaneously develop a form of autoimmune diabetes resembling insulin dependent diabetes mellitus (IDDM) in humans. IDDM results from central destruction of the insulin-producing beta-cells of the pancreatic islets. Herein, we report that the outbreak of IDDM in BB/E rats is preceded by the spontaneous development of an anti-idiotypic antibody to a particular antibody to insulin made by the rats. This anti-idiotype, designated anti-DM-id, behaves as an antibody to the insulin-hormone receptor. Thus, a spontaneous anti-idiotypic antibody network whose products can affect the peripheral utilization of insulin seems to accompany the central destruction of beta-cells in developing IDDM. PMID- 2245875 TI - Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats. AB - The action potential duration (APD) of ventricular muscles obtained from diabetic animals is reported to be prolonged. We studied the effect of varied periods of diabetes on APD prolongation using isolated ventricular papillary muscles from streptozocin-injected rats. We found that a diabetic period greater than 30 wk was necessary for the evolution of significant prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40 mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and compared the findings with those from control rats. Transmembrane potentials were recorded with conventional glass microelectrodes. Under normoxic conditions, the APDs of diabetic muscles were significantly prolonged, the maximum upstroke velocity of action potentials tended to be decreased, and the resting membrane potential was not changed significantly compared with controls. The first hypoxia (20 min) shortened the APD in both diabetic and control rats but more so in diabetic rats, thereby making the APD of diabetic rats virtually identical to the control rat APD during the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced changes were almost recovered. The second hypoxia (20 min) produced more severe shortening of the APD in both muscle types, and the effect was again far greater in diabetic rats than controls, ending with a reversed sequence of APDs and the APD of diabetic muscles much shorter than the controls. Excessive shortening of APD in diabetic muscles during hypoxic conditions was speculated to be due to greater increases in the outward K+ current through ATP-regulated K+ channels that may be secondary to the more severe reduction of intracellular ATP concentrations in diabetic versus control hearts. PMID- 2245876 TI - Application of chronic intravascular blood glucose sensor in dogs. AB - An intravenous glucose sensor was implanted in six dogs for 1-15 wk. The glucose sensor is a flexible cylinder, approximately 0.2 cm diam and 30 cm long, with a tip containing immobilized glucose oxidase and catalase coupled to a potentiostatic O2 sensor. The sensor and a similar O2 reference sensor were implanted in the superior vena cava near the entrance of the right atrium. The sensor response was conveyed externally either by a telemetry system implanted nearby, surgically accessed leads, or chronically maintained percutaneous leads. Summing over the six implants, there was a total implantation period of 333 days during which glucose sensors were functional on demand. The sensor response showed agreement with conventionally assayed blood samples after accounting for a response lag. Sensor response to glucose showed little change over the implant period. Biocompatibility, enzyme lifetime, O2 availability, O2 sensor stability, and biochemical interference were not limitations. Results demonstrated that this sensor can function effectively as an implant in dogs for a period of months and has the potential for long-term operation. PMID- 2245877 TI - Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis. AB - The possible causes of the enhanced risk for coronary heart disease (CHD) were examined in morbidly obese women with normoglycemia, impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) before and after gastric bypass surgery. Compared with age-matched lean women, plasma lipid and apolipoprotein concentrations of the obese women before surgery favored atherogenesis. The risk for CHD may further be exacerbated in the IGT and NIDDM groups by the prevalence of smaller and denser low-density-lipoprotein (LDL) particles. LDL size correlated negatively with plasma insulin levels independent of triglyceride levels, age, or body mass index (BMI). After surgery, BMI, plasma insulin, and triglyceride levels decreased, but LDL size increased, and LDL density decreased. Neither cholesterol nor LDL cholesterol levels were affected after surgery, but high-density-lipoprotein cholesterol was increased in all patients after surgery. Although the mechanisms underlying the changes in the properties of LDL could not be determined from this study, these changes appear to be of benefit in reducing CHD risk in these patients. PMID- 2245878 TI - Role of two types of glucose transporters in enlarged adipocytes from aged obese rats. AB - The mechanism of insulin-resistant glucose-transport activity in enlarged aged adipocytes was examined. Glucose-transport activity was assessed by measuring 3-O methylglucose transport and the concentration of HepG2 erythrocyte/glucose transporter (GLUT1), and the muscle/adipose tissue transporter (GLUT4) was estimated by immunoblotting. Basal glucose-transport activity increased 6.3 fold/cell but remained constant per unit cellular surface area due to cell enlargement. Maximal insulin-stimulated transport activity remained constant per cell but decreased per unit cellular surface area. On a per protein basis, GLUT1 and GLUT4 from aged rats decreased to approximately 60 and 10% of those from young rats, respectively. However, when the protein content of each fraction and the recoveries of marker enzymes were used for estimating the amount of transporters in intact adipocytes, the amount of GLUT1 per cell remained relatively constant, whereas that of GLUT4 decreased. In basal cells from young rats, 31% of the total GLUT1 per cell was located in the plasma membrane, whereas in those from aged rats, 63% was located in the plasma membrane. Thus, in comparing basal adipocytes from aged rats with those from young rats, GLUT1 per cell in the plasma membrane increased 2.8-fold, but this increase was less than that of transport activity (6.3-fold). In basal cells from young rats, 8% of the total GLUT4 was located in the plasma membrane, and a 4.5-fold increase was observed with insulin treatment, but the amount of GLUT4 in each fraction from aged rats markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245880 TI - Recognition of hypertension and abnormal blood pressure burden with ambulatory blood pressure recordings in type I diabetes mellitus. AB - Ambulatory blood pressure (AMBP) measurements were obtained at 20-min intervals for 24 h in 25 subjects with insulin-dependent (type I) diabetes mellitus and 21 control subjects. The diabetic patients had normal kidney function (glomerular filtration rate 112.1 +/- 7.2 ml.min-1.1.73 m-2, renal plasma flow 459.0 +/- 23.4 ml.min-1.1.73 m-2) and were normotensive according to standard sphygmomanometer examinations. Mean +/- SE AMBP (systolic/diastolic in mmHg) measurements in diabetic patients (24 h, 131.7/77.2 +/- 2.9/1.8; 0600-2200, 132.3/78.4 +/- 2.9/3.4; 2200-0600, 125.1/75.7 +/- 3.9/3.4) significantly exceeded control values during all times (24 h, 121.8/70.3 +/- 2.9/1.9; 0600-2200, 120.7/71.8 +/- 2.6/2.0; 2200-0600, 108.2/61.5 +/- 6.6/2.7). Mean 24-h AMBP exceeded 135/85 mmHg in 49% of diabetic patients. The same threshold of 135/85 mmHg was used to determine the prevalence of abnormal measurements per time period (pressure burden). Pressure burden was increased twofold in diabetic patients compared with control subjects. Mean AMBP was significantly reduced at night in control subjects but not in diabetic patients. Changes in blood pressure were not related to kidney function in diabetic patients. AMBP recordings uncovered an increased prevalence of abnormal mean blood pressure, increased pressure burden, and a lack of diurnal variation of blood pressure in subjects with type I diabetes mellitus. These findings have important implications for early intervention strategies in diabetes mellitus because AMBP recordings correlate well with end-organ damage. PMID- 2245879 TI - Mild hypoglycemia and impairment of brain stem and cortical evoked potentials in healthy subjects. AB - To evaluate the impact of mild hypoglycemia on CNS function in healthy adults, we measured brain stem auditory evoked potentials and P300 potentials (elicited by cognitive processing of auditory stimuli) during hypoglycemic or euglycemic insulin clamps (80 mU.m-2.min-1). In the hypoglycemic clamp study (n = 8), plasma glucose was allowed to fall from 4.6 to 3 mM in hourly approximately 0.5-mM steps and subsequently returned to euglycemic baseline levels. In the euglycemic clamp study (n = 8), plasma glucose was maintained at baseline levels throughout. Neither brain stem nor P300 responses changed during the euglycemic control study; symptoms and counterregulatory hormones were also unaffected. During the hypoglycemia study, epinephrine and growth hormone rose once plasma glucose reached 3.4 +/- 0.1 mM. Brain stem and P300 potentials remained unchanged until the 3-mM glucose step, when neurophysiological changes suddenly developed in conjunction with reported symptoms. At this glucose level, the wave V component of the brain stem potential was selectively altered in 7 of 8 subjects. Furthermore, P300 latency significantly increased, and amplitude diminished. Changes in both brain stem and cortical (P300) responses reversed when euglycemia was restored. We conclude that modest reductions in plasma glucose (to 3 mM) produce marked alterations in both brain stem and cortical responses to auditory stimuli. These changes in neural function appear at the same time as symptoms and follow rather than precede the rise in counterregulatory hormones during hypoglycemia. Our data suggest that the adverse effects of mild hypoglycemia on brain function are not limited to higher centers but also involve the brain stem. PMID- 2245881 TI - Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy. AB - We compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted. PMID- 2245882 TI - Coupling of beta-cell desensitization by hyperglycemia to excessive stimulation and circulating insulin in glucose-infused rats. AB - Nondiabetic rats were infused with glucose for 48 h to maintain moderate or marked hyperglycemia (mean blood glucose 13.2 +/- 0.7 or 22.8 +/- 0.3 mM, respectively). The two levels of hyperglycemia increased plasma insulin levels severalfold but decreased the insulin response to 27 mM glucose by 19 and 95%, respectively, versus saline infusion. Diazoxide (5 mg.kg-1.h-1), when continuously infused during the hyperglycemia protocols, completely inhibited the glucose-induced rise in plasma insulin levels. Diazoxide transformed beta-cell insensitivity to stimulation: glucose-induced insulin release was thus increased 318% after moderate hyperglycemia and 707% after marked hyperglycemia. These stimulatory effects of diazoxide were reversed by exogenous insulin infusion (8 or 2 U/24 h) in a dose-dependent manner. It is concluded that excessive beta-cell stimulation rather than glucotoxicity underlies hyperglycemia-induced beta-cell insensitivity. Effects of hyperinsulinemia can form part of the mechanisms whereby excessive stimulation affects beta-cell secretion. PMID- 2245883 TI - Why family medicine is always cross-cultural medicine. PMID- 2245884 TI - The association between peer consultations and three aspects of clinical competence. AB - The relationship between the clinical competence of general practitioners and the degree of peer consultation about diagnostic and therapeutic problems was studied. Three aspects of clinical competence are discerned: attention paid to somatic aspects, patient-orientation and risk of unnecessary harm of the management. Clinical competence has been measured by a written simulation of patient-doctor encounters using five patients and assessment procedures in a study with a correlational design. For this study 49 subjects were selected from a population of 184 GPs who completed their vocational training in general practice at the University of Utrecht between 1975 and 1980. They were selected from those who consult their colleagues frequently and systematically about a variety of patients' problems and from those who do so little or not at all. The 49 subjects did not differ from the remainder in several relevant aspects such as practice setting, subscription to medical journals, etc. The 49 GPs are relatively consistent in the quality of attention they pay to somatic aspects. The consistency with regard to the two other aspects is rather low, especially regarding the risk of unnecessary harm. Attention paid to somatic aspects is connected with patient orientation. The latter is also connected with risk of unnecessary harm, but the former is not. The three aspects are more or less separate aspects of clinical competence. Peer consultation has a direct relationship with quality of attention paid to somatic aspects; GPs who do not consult among peers anyway display a lower quality of attention to somatic aspects in comparison to those who do so.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245885 TI - Competence and performance: two different concepts in the assessment of quality of medical care. AB - In the debate about 'what is a competent general practitioner?' little attention has been paid ot the actual practice situation of general practitioners. This paper, based on the 18 most important studies in the literature about medical competence, tries to re-initiate this debate by proposing a clear distinction between 'competence', (what a physician is capable of doing) and 'performance' (what a physician does in his day-to-day practice). With this distinction we looked at whether studies defined both competence and performance, how they dealt with these concepts, what measurement instruments were used and what the conclusions of the studies were. Although it is the common reasoning that competence is a good predictor of performance this concept could not be affirmed. This survey shows that the majority of studies use wrong concepts and come to invalid conclusions. With the empirical distinction between competence and performance however, this paper proposes new directions for the quality assessment of general practitioners. PMID- 2245886 TI - Acute bronchitis: general practitioners' views regarding diagnosis and treatment. AB - A survey was conducted among 800 Dutch general practitioners to establish their views on the diagnosis and treatment of bronchitis and related disorders with reference to 12 theoretical patients. The answers of the 467 respondents (response rate 60%) showed no clear relationship between signs and symptoms of the patients and the diagnosis made. In the authors' opinion the diagnosis of pneumonia was made too often. The decision whether or not to prescribe an antibiotic for a coughing patient was based in part on the diagnosis made, but in part it was also made on the basis of the signs and symptoms, irrespective of the diagnosis. The authors have the impression that general practitioners tend to prescribe antibiotics too quickly to coughing patients. There is a need for guidelines for diagnosis and treatment of patients with acute bronchitis and related conditions. PMID- 2245887 TI - Vitamin/mineral supplement use among general practice patients in the United Kingdom. AB - Many patients take vitamin/mineral supplements, sometimes in doses which may cause toxicity. A survey of 186 patients in one general practice showed that 44% consumed supplements; almost half of these took them daily, and over half had taken them for longer than a year. Younger patients were more likely to take vitamins than older ones. Multivitamins were the most frequently used supplement, followed by iron and vitamin C. Major reasons patients cited for supplement use were to ensure good nutrition, to prevent illness, and for tiredness/fatigue. Patients were most influenced in their decision to take vitamins by family and friends rather than by doctors. General practitioners may find it valuable to include questions about vitamin/mineral supplement use in the medical history. PMID- 2245888 TI - Evaluation of the telephone advisory activity at Swedish primary health care centres. AB - The telephone advisory function was evaluated by interviewing 100 persons from each of five Swedish health centres one week after they had contacted the health centre for telephone advice. Altogether 497 telephone calls were registered during the study period, and 494 (99%) of those who called could be contacted. Of those who had been given advice about self-care (in all 173 pieces of advice to 98 subjects), 98% stated that they had followed the advice given. In the total series, 91% of the subjects stated that they were content with the contact with the telephone advisers. The majority of those who were not content with the contact had been recommended self-care or given an appointment time with a delay of more than one week. In 10% of the cases the telephone advisers (all of them nurses) considered that they could not give adequate advice because of lack of appointment times with the doctor. In 4% of the cases decisions were made which agreed with the subject's wishes but were not in agreement with what the nurse considered most adequate. When a suitable appointment time was available (422 calls), all but three calls were considered as handled medically correctly, and all but two cases were considered to have been referred to correct level of care. It was concluded that the nurses handled the telephone advisory service in an adequate way. PMID- 2245889 TI - Recognition of depression in the elderly: a comparison of general practitioner opinions and the Geriatric Depression Scale. AB - As part of a larger study, 133 subjects aged 70 years and over were screened for depression using the Geriatric Depression Scale, a 30-item questionnaire, as the screening instrument. Cognitive status was assessed using the Mini Mental State Examination. The subject's own general practitioner was asked his/her opinion as to whether the subject was depressed. Poor agreement was found between depression as measured by the Geriatric Depression Scale and the general practitioner's assessment. Possible reasons for this include the difficulty of finding a satisfactory operational definition of depression for use by general practitioners, the problems of identifying depression in the elderly, the arbitrary definition provided by the scale and the confounding of depression, as measured by the scale, with cognitive status. PMID- 2245890 TI - Detection of emotional problems in the primary care clinic. AB - Emotional problems are an important component of general morbidity in primary care settings. Research on the sensitivity of primary care physicians to such problems is, however, scanty. This study examines the prevalence of emotional problems among 776 patients in primary care clinics in Israel using the GHQ-28 and as detected by their physicians. Hypotheses were tested relating to physician and practice characteristics and the extent to which they affect the matching of the two methods of problem identification. Using the GHQ, 69% of the patients were classified as 'cases'; physicians identified 31% of the patients as 'cases'. Specialist status in family medicine, interest and belief in the importance of emotional health, good communication, a low patient load and familiarity with the patient all predicted a better match of physician classification to GHQ-defined 'caseness'. The implications of these findings for ongoing medical education are briefly discussed. PMID- 2245891 TI - Premenstrual syndromes defined by symptom-sets. AB - An analysis is made of the pattern of presenting premenstrual symptoms in randomly selected general practice patients from the Wellington region, New Zealand. Participants, 1826 healthy women 16-54 years old whose characteristics were reasonably representative of the adult female population, were asked about their general, obstetrical and gynaecological health. For the 1456 women who had menstruated within the last month or so, detailed questions were asked about the last menstrual cycle. Each woman was assigned to one of seven premenstrual symptom sets. Three groups had 'pure' symptoms, ie a predominant single symptom (breast tenderness, bloating or irritability). Three groups had 'mixed' symptom sets. The largest of the 'mixed' groups was formed by the women who reported breast tenderness, bloating and irritability together with tension and depression. Women in this group were most likely to rate their symptomatology as severe. The last group contains a large number of women with miscellaneous symptoms. Characteristics of these groups are outlined. The study highlights the importance of distinguishing among premenstrual syndromes as this can foster more effective clinical management. PMID- 2245892 TI - The Medical Outcomes Study Instrument (MOSI)--use of a new health status measure in Britain. AB - The Medical Outcomes Study Instrument (MOSI), a 20 item functional health status measure was sent to all women aged 30-40 years (n = 486) in a General Practice (list size 6447). There was a 73% response rate to two mailings. Lower scores on all six dimensions of the MOSI were associated with the number of diagnoses and identified mental illness on the patient summaries, unemployment and with positive scores on the Nottingham Health Profile. In two categories, General Health Perceptions and Mental Health, the scores were lower for those on long term medication. The paper suggests that the MOSI may be a candidate for Health Status measurement in research and audit in primary care, but further research is required. PMID- 2245893 TI - Should family doctors screen asymptomatic children for high blood pressure? AB - Whereas the United States Task Forces on Blood Pressure Control in Children have recommended annual blood pressure screening in all children, a working party of the British Hypertension Society has formed the opposite opinion. Relevant literature is reviewed here, and the conclusion reached that on epidemiological and ethical grounds, screening children for hypertension cannot at present be justified. PMID- 2245894 TI - Alternative medicine and general practitioners in The Netherlands: towards acceptance and integration. AB - A questionnaire on alternative medicine was sent to 600 general practitioners in the Netherlands. Most of the 360 (60%) GPs who replied expressed on interest in alternative practice; and 47% revealed that they used one or more alternative methods themselves, most often homoeopathy. However, the number of patients given alternative treatment by each doctor was small. Almost all (90%) of the GPs referred patients to alternative practitioners. There is no reason to assume that GPs make use of alternative methods just to meet their patients' wishes. A majority of the respondents thought that these therapies included ideas and methods from which the regular methods might benefit. Actual contacts with alternative practitioners are mostly limited to those practicing acupuncture, homeopathy and manipulative medicine with a regular medical or paramedical education. The integration of alternative medicine within the medical system goes hand in hand with its acceptance by general practitioners. Contact with medically or paramedically qualified practitioners has hardly any legal implications for individual general practitioners. PMID- 2245895 TI - Liver transplantation: the shadow side. AB - For a relatively large number of patients with liver disease, a liver transplant does not always provide a successful solution. What does confrontation with this modern technology mean for those involved? We interviewed 30 relatives of patients who had died after they had been turned down for a transplant, or during or shortly after a liver transplant operation performed in the Groningen Liver Transplant Programme. Quantitative data were obtained by means of a questionnaire. One-third of the respondents were of the opinion that the patient would have been better off if he/she had not entered the programme. Over half found the loss more difficult to accept because the patient had been involved in the programme. Nevertheless, many had the feeling of satisfaction that everything possible had been done. However fruitful transplantation technology may be for a specific group of patients, it also involves undesirable side-effects which should be included in the careful judgement of this technology. PMID- 2245896 TI - Contraceptive services for Asian women in UK. PMID- 2245897 TI - [The clinical characterization and prognostic significance of episodes of transient myocardial ischemia in patients with a recent myocardial infarct]. AB - The incidence and prognostic significance of silent myocardial ischemia were assessed in 175 patients who survived a first acute myocardial infarction (AMI). This was done by means of a 24-hour continuous ECG monitoring which was performed before discharge. Twenty-six out of 175 patients (14.8%) showed one episode or more of S-T segment depression; 19 of these reported no pain at all while the other 7 reported both painful and painless episodes. A total of 65 ischemic episodes were registered; of these 53 (81.5%) were painless and 12 (18.5%) were painful. No difference in the duration of ischemic episodes or in heart rate at the onset of S-T segment depression was detected for painless or painful episodes. The S-T segment depression episodes showed a peak in the morning but were higher in the afternoon and this circadian pattern was statistically significant both with regard to duration (p less than 0.05) and to the number of episodes (p less than 0.05). Cardiac death occurred in 5 of the 26 patients (19.2%) with S-T segment depression during continuous ECG monitoring, and in 5 of the 149 (3.4%) without S-T segment depression (p less than 0.01). In patients with ischemia duration greater than 60 min/24 hours, the mortality rate was higher (p less than 0.05). No cardiac events (unstable angina, non-fatal re infarction, balloon angioplasty and/or coronary by-pass) occurred in 117 out of 149 patients (78.5%) without ST-segment depression, while these events were observed in 13 out of the 26 patients (50%) with ischemic episodes during Holter monitoring (p less than 0.01). Sensitivity and specificity of S-T segment depression was respectively 29.3 and 89.5% for cardiac death and cardiac events considered together.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245898 TI - [Ventricular arrhythmias in the acute phase of myocardial infarct and in the postinfarct. A 1-year follow-up]. AB - A total of 90 AMI patients (80 male, 10 female; mean age: 62 years, range: 36-70 yrs) who were admitted to the coronary care unit within six hours of the onset of symptoms were evaluated for the following: the incidence and variability of complex ventricular ectopic beats (classes Lown III-V) in the acute, subacute and chronic phases of myocardial infarction. The diagnostic utility of Holter monitoring and treadmill exercise testing was compared so as to reveal complex ventricular ectopic beats. The relation between complex ventricular ectopic beats and left ventricular dysfunction was determined using the echocardiographic technique (ejection fraction, fractional shortening). The hospital mortality rate was 6.6% (6/9 patients) while the post-hospital mortality rate was 3.5% (3/84 patients). The prevalence rate of complex ventricular ectopic beats detected by Holter monitoring was respectively: 85.5% (77/90 patients) in the acute phase, 8.5% (7/80) at the 72nd hour, 18.5% (15/80) in the pre-discharge phase. At 1, 3, 6 and 12 months the prevalence rate was respectively 35% (27/77 patients), 28.8% (22/77), 24.6 (19/77), 24.6% (19/77). A high variability in arrhythmic groups was found. Each group was composed of new arrhythmic patients and stable arrhythmic patients, in addition to a small number of patients who were arrhythmic in the preceding control but no arrhythmic in the following control. This specific analysis of various groups revealed that the pre-discharge phase is the period with the highest number of "stable arrhythmic" patients (4 Holter positive out of 5) compared to the 1st month (3 Holter positive out of 4) and the 3rd month (2 Holter positive out of 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245899 TI - [The variability and prognostic significance of ventricular hyperkinetic arrhythmias in the postinfarct: the considerations after the CAST. Cardiac Arrhythmia Suppression Trial]. PMID- 2245900 TI - [A comparison between mitral and aortic outputs evaluated by Doppler echocardiography in a group of healthy subjects: false regurgitation]. AB - Doppler echocardiography is a potentially useful tool for the non invasive evaluation of cardiac output and, therefore, for the quantitative assessment of valvular regurgitation. The aim of our study was to establish the presence of possible pitfalls in the evaluation of mitral and aortic regurgitant fraction obtained by Doppler echocardiography comparing the cardiac output measured at the level of the mitral and aortic valve. For this purpose 19 healthy volunteers, aged between 14-68 years, were studied. Stroke volume and cardiac output were calculated at the level of the mitral and aortic valve. The methods we used for the measurement of both the mitral and aortic cardiac output had already been validated and presumes that the shape of the valve annulus, is circular. No statistically significant differences were found between the parameters obtained at the two different valvular levels. Furthermore, cardiac output values correlated fairly well (r = 0.83, ESS = 0.78 l/min). In 9 subjects the aortic cardiac output was greater than the mitral one, while in the others mitral cardiac output was greater. The average of the differences between the two cardiac outputs was 0.58 +/- 0.48 l/min with a regurgitation fraction of 9.5 +/- 7.9%. Our results show that the mitral and aortic stroke volume and cardiac output, as measured by Doppler echocardiography (considering a circular shaped valve annulus, are not statistically different and correlate fairly well in our normal subjects. Nevertheless, we observed a certain degree of variability between the mitral and the aortic cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245901 TI - [The cardiovascular toxicity of interleukin-2: the pathogenic mechanisms and treatment]. PMID- 2245902 TI - [Cardiac lipoma in a patient with diffuse subcutaneous lipomatosis. Nuclear magnetic resonance diagnosis]. AB - We describe a case of left ventricular intramyocardial lipoma in a patient with diffuse subcutaneous lipomatosis. The diagnosis was suspected on the basis of a two-dimensional echocardiographic examination that revealed a hyperechogenic mass within the left ventricular wall. Magnetic resonance imaging showed a homogeneous high signal mass thus indicating the presence of a benign lipoma. This report shows the ability of two-dimensional echocardiography and magnetic resonances imaging in detecting, localizing and characterizing left ventricular lipomas without the use of more invasive studies. PMID- 2245903 TI - [Cardiac angioma. A case report and review of the literature]. AB - We report the case of a 4-year old child who underwent echocardiographic examination which revealed a multicystic tumor mass involving the infero-lateral wall of the left ventricle. It was necessary to perform a biopsy to make a reliable diagnosis. Histological studies indicated haemangiomatous and fibrous tissue of benign origin. The extensive involvement of the left ventricular free wall did not favour resection so we advised periodic clinical examination and Holter ECG to highlight any eventual occurrence of hypo or hyperkinetic arrhythmias. PMID- 2245904 TI - [Disorders of atrioventricular conduction in Ebstein's anomaly in an adult. A report of 5 cases]. AB - From the literature we find that the most frequent electrical alterations in Ebstein's anomaly are: the abnormal right atriogram; ventricular pre-excitation; supraventricular tachycardia; right bundle branch block and lengthening of the PR tract. These alterations are also present in cases of Ebstein's anomaly diagnosed in adults. The study of the activation of the right ventricle, which offers a variety of forms of development, is a source of particular interest. We report five cases which have come to our attention, in which greater disturbances of the atrioventricular block were present. This aspect has not yet been clearly reported in the literature. PMID- 2245905 TI - [The prognostic assessment of dilated cardiomyopathy: a follow-up of 138 patients]. AB - A total of 138 patients with idiopathic dilated cardiomyopathy were assessed and followed-up between July 1973 and October 1985 in order to evaluate prognostic risk indicators. Of these 102 were male and 36 were female with a mean age of 49.1 years. Each patient underwent physical examination, electrocardiography, echocardiography, cardiac catheterization and coronary angiography. The mortality rate was low for the first 3 years (respectively 8, 12.5 and 20%) while it was 57.5 at the end of the 5-year follow-up period. Univariate analysis at the time of the diagnosis revealed that five factors were predictive of the clinical course at the end of the fifth year: the NYHA functional class IV (p less than 0.0001); LV ejection fraction less than 0.30 (p less than 0.01); left ventricular failure, bi-ventricular failure and left ventricular end-diastolic pressure greater than 20 mmHg (p less than 0.05). Multivariate analysis was used to determine which combination of factors could most accurately predict survival. The most important prognostic factor was again the IV NYHA functional class (p less than 0.01) and, to a lesser degree, left ventricular end-diastolic pressure (p less than 0.05). The present study underlines that the survival rate of patients with dilated cardiomyopathy depends upon the selection of patients. This can explain the low 3-year mortality found in our patients. The NYHA functional class may be a useful practical guide for cardiac transplantation. PMID- 2245906 TI - [Oral anticoagulants: their pharmacology, mechanism of action and therapeutic control]. PMID- 2245907 TI - [Heparin: its mechanism of action and use in cardiology]. PMID- 2245908 TI - [The surveillance of the anticoagulated patient: a multidisciplinary problem]. PMID- 2245909 TI - [A propos of GISSI 2]. PMID- 2245910 TI - "Joy of the worm". PMID- 2245911 TI - The DAF2-2 mutation, a dominant inhibitor of the STE4 step in the alpha-factor signaling pathway of Saccharomyces cerevisiae MAT alpha cells. AB - A dominant mutation (DAF2-2) resulting in resistance to the mating pheromone alpha-factor in Saccharomyces cerevisiae MATa cells was identified and characterized genetically. Whereas wild-type cells induce a high level of the FUS1 mRNA from a low baseline on exposure to alpha-factor, DAF2-2 cells were constitutive producers of an intermediate level of FUS1 RNA; the level was increased only modestly by alpha-factor. FUS1 constitutivity required STE4, STE5 and STE18, but did not require STE2, the alpha-factor receptor gene. DAF2-2 suppressed the alpha-factor supersensitivity of a STE2 C-terminal truncation, and suppressed lethality due to scg1 mutations. Thus DAF2-2 may act by uncoupling the signaling pathway from alpha-factor binding at some point in the pathway between Scg1 inactivation and the action of Ste4, Ste5 and Ste18; this uncoupling might occur at the expense of partial constitutive activation of the pathway. DAF2-2 suppressed the unconditional cell-cycle arrest phenotype of a dominant "constitutive signaling" allele of STE4 (STE4Hpl), although the constitutive FUS1 phenotype of DAF2-2 was suppressed by ste4 null mutations; therefore DAF2-2 may directly affect the performance of the STE4 step. PMID- 2245912 TI - stf1: non-wee mutations epistatic to cdc25 in the fission yeast Schizosaccharomyces pombe. AB - In Schizosaccharomyces pombe, cdc25 is a cell cycle regulated inducer of mitosis. wee1 and phenotypically wee alleles of cdc2 are epistatic to cdc25. Mutant alleles of a new locus, stf1 (suppressor of twenty-five), identified in a reversion analysis of conditionally lethal cdr1-76 cdc25-22 and cdr2-96 cdc25-22 double mutant strains, also suppress both temperature-sensitive and gene disruption alleles of cdc25. These mutants, by themselves, are phenotypically indistinguishable from wild type strains; hence they represent the first known mutations that are epistatic to cdc25 and do not display a wee phenotype. stf1 genetically interacts with other elements of mitotic control in S. pombe. stf1-1 is additive with wee1-50, cdc2-1w and cdc2-3w for suppression of cdc25-22. Also, like wee1- and cdc2-w, stf1- suppression of cdc25 is reversed by overexpression of the putative type 1 protein phosphatase bws1+/dis2+. Interaction with various mutants and plasmid overexpression experiments suggest that stf1 does not operate either upstream or downstream of wee1. Similarly, it does not operate through cdc25 since it rescues the disruption. stf1 appears to encode an important new element of mitotic control. PMID- 2245913 TI - Properties of a class of genes required for ray morphogenesis in Caenorhabditis elegans. AB - We have identified eight mutations that define at least five terminal differentiation genes (ram genes) whose products are required during the extension of the male-specific ray sensilla in Caenorhabditis elegans. ram gene mutations result in morphological abnormalities in the sensory rays but do not appear to interfere with ray functions. A similar ray morphology phenotype was observed in males harboring mutations in three previously defined genes, dpy-11, dpy-18 and sqt-1, that also affect body shape. One of these genes, sqt-1, is known to encode a collagen. Mutations in different ram genes failed to complement, from which we infer that their gene products functionally interact. For one ram gene, failure to complement was shown to result from haploinsufficiency. Intergenic noncomplementation did not extend to the body morphology genes. The temperature-sensitive periods of both ram and body morphology mutations corresponded to the period of development in which ray extension occurs. We propose that ram gene products act together in a critical interaction between the rays and the cuticle required for wild-type ray morphology. PMID- 2245914 TI - The unc-45 gene of Caenorhabditis elegans is an essential muscle-affecting gene with maternal expression. AB - We have isolated three novel alleles of the unc-45 locus in C. elegans, that are recessive lethals. Two of these alleles, when homozygous, result in a nearly total loss of muscle contraction with a concomitant arrest of development and a displacement of muscle cells. The third allele is similar, but showed maternal rescue by a wild-type allele. All previously identified unc-45 alleles were temperature sensitive and, although they produced paralysis of adult animals, all were homozygous viable. Prior genetic studies with these temperature sensitive alleles had suggested that at least one function of the unc-45 gene product was to interact with the major myosin heavy chain isoform, MHC B, of body wall muscles. Our observations of the lethal alleles suggest that the unc-45 product normally interacts with additional muscle components in both the body wall and pharyngeal muscles. In particular, we suggest that the unc-45 product might interact with all four myosin heavy chains: MHC B; MHC A; and the pharyngeal isoforms, MHC C and MHC D. Maternal rescue of the lethality of the third allele shows that the unc-45 gene product is present in the oocytes, although it may not be necessary until late in development when myofilaments begin to assemble. PMID- 2245915 TI - Sex-related differences in crossing over in Caenorhabditis elegans. AB - In the nematode Caenorhabditis elegans, hermaphrodite recombination has been characterized and is the basis of the genetic map used in this organism. In this study we have examined male recombination on linkage group I and have found it to be approximately one-third less than that observed in the hermaphrodite. This decrease was interval-dependent and nonuniform. We observed less recombination in the male in 5 out of 6 intervals examined, and no observable difference in one interval on the right end of LG I. Hermaphrodite recombination frequencies are the result of recombination in two germlines; oocyte and hermaphrodite spermatocytes. We have measured recombination in the oocyte and have found it to be approximately twofold lower than that calculated for hermaphrodite spermatocytes and not significantly different from the male spermatocyte frequency. Thus, recombination frequencies appear to be a function of gonad physiology rather than the sex of the germline. Evidence from experiments examining the effect of karyotype on recombination in males sexually transformed by the her-1 mutation into XO hermaphrodites (normally XX), suggests the sexual phenotype rather than genotype determines the recombination frequency characteristic of a particular sex. Hermaphrodite recombination is known to be affected by temperature, maternal age, and the rec-1 mutation. We have examined the effect of these parameters on recombination in the male and have found male recombination frequency increased with elevated temperatures and in the presence of Rec-1, and decreased with paternal age. PMID- 2245916 TI - The molecular basis of brown, an old mouse mutation, and of an induced revertant to wild type. AB - The murine b locus encodes the tyrosinase related protein, TRP-1, a putative membrane-bound, copper-containing enzyme having about 40% amino acid identity with tyrosinase. The protein is essential for production of black rather than brown hair pigment. We show that skin of mutant brown mice contains the same amount of TRP-1 mRNA as wild type. On sequencing the coding region of the mutant mRNA we find four nucleotide differences from the wild-type (Black) sequence. Two of these differences result in different amino acid residues encoded by the brown allele. By sequencing the TRP-1 gene from a mouse in which a reversion from brown to Black has been induced by ethylnitrosourea we are able to show that only one of these amino acid changes, which substitutes a tyrosine for a conserved cysteine, is the cause of the brown phenotype. This mutation is adjacent to another cysteine at which, in the analogous position in tyrosinase a mutation results in the albino phenotype. The sequence of the revertant is the first report of DNA sequence of an ethylnitrosourea-induced genetic change in mouse. PMID- 2245917 TI - Characterization of TRP-1 mRNA levels in dominant and recessive mutations at the mouse brown (b) locus. AB - The mouse brown locus encodes a putative membrane-bound metalloenzyme, tyrosinase related protein-1 (TRP-1). We have examined the effect on mRNA expression of the locus of a number of mutant alleles. The common null mutant allele, brown, produces wild-type levels of TRP-1 mRNA, which is nonfunctional. Another recessive allele, cordovan-Harwell, has an intermediate, dark-brown phenotype and produces only very low levels of presumably normal TRP-1 mRNA. Two dominant alleles appear to act by killing the melanocyte in which they are expressed. One of them, Light, has normal size and amounts of TRP-1 mRNA. The other, White-based brown, produces no detectable TRP-1 mRNA. It has a gross DNA rearrangement at the 5' end, and we speculate that this results in activation of transcription of sequences not usually seen in melanocytes, and that this is toxic to the cell. The relationship between phenotype and molecular structure at the locus is discussed, and we draw some general principles applicable to other developmental genes. PMID- 2245918 TI - Opportunities for consultation-liaison research in the 1990s. PMID- 2245919 TI - Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs. AB - Among a sample of 767 high utilizers of health care, 51% were identified as distressed by an elevated score on the SCL anxiety and depression scales, the SCL somatization scale, or by their primary-care physician. These distressed high utilizers were found to have a high prevalence of chronic medical problems and significant limitation of activities caused by illness. In the prior year, they made an average of 15 medical visits and 15 telephone calls to the clinic. The Diagnostic Interview Schedule was completed on 119 distressed high utilizers randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The following DSM-III-R disorders were most common: major depression 23.5%, dysthymic disorder 16.8%, generalized anxiety disorder 21.8%, and somatization disorder 20.2%. Two thirds had a lifetime history of major depression. The examination resulted in an improved diagnostic assessment for 40% of intervention patients and a revised treatment plan for 67%. PMID- 2245920 TI - Family systems intervention and physical illness. AB - Family systems theory provides the physician with a comprehensive paradigm to investigate the social and interpersonal context of physical illness. All physical illnesses, particularly life-threatening and chronic ones, profoundly affect the family life of the patient, and the changed family circumstances in turn have impact upon the physically ill patient. This reciprocal interaction between the illness and the family system varies according to the onset, course, outcome, and level of disability. This paper discusses the general application of family systems theory to physical illness as well as the description of the family dimension of acute life-threatening illness, AIDS, chronic illness, chronic neurologic disease, dementia, chronic pain, and cancer in children. We propose that an operational knowledge of theoretical concepts and technical competencies of family systems theory can enhance the therapeutic reach of physicians and other health professionals. PMID- 2245921 TI - The pregnant psychiatric inpatient: a missed opportunity. AB - The authors describe a group of pregnant psychiatric patients admitted to a psychiatric service in an urban hospital. A high rate of involuntary admission (44%), homelessness (36%), and substance abuse (64%) was noted. In this group of high-risk obstetric patients, we identified risk factors associated with noncompliance with ongoing prenatal care. Brief psychiatric hospitalization can be an important aspect in improving obstetric outcome by providing an opportunity to collect obstetric information and promote ongoing prenatal care. PMID- 2245922 TI - Hypnosis on a consultation-liaison service. AB - The use of hypnosis was demonstrated on a psychiatric consultation-liaison service (CLS) in a broad spectrum of medically hospitalized patients. Hypnosis was employed as an adjuvant measure to traditional medical and psychologic treatment modalities. Tapes for autohypnosis were used for reinforcement. Twenty nine women and eight men from 24 to 75 years of age were hypnotized for relief of depression, pain, anxiety, or side-effects from chemotherapy. Results were excellent (total to almost total relief of symptoms) in 68% of the patients, fair in 22%, and poor in 11% with no differences among the results with the various conditions. This report demonstrates that hypnotherapy can be an extremely useful tool in the medical management of patients on a CLS. PMID- 2245923 TI - Training of primary health care medical officers in mental health care. Errors in clinical judgment before and after training. AB - This investigation examined the nature and frequency of errors in clinical judgment that were displayed by primary health care medical officers before and after short-term training in mental health care. Thirty-nine medical officers who underwent inservice training for 2 weeks were evaluated using standardized case vignettes. Before the training, doctors displayed a sizable percentage of major and minor errors, which dropped significantly following training. Errors were not unique to psychiatric presentations alone, but occurred with respect to vignettes representing physical disorders as well. The results on the whole demonstrate a satisfactory gain in clinical skills of medical officers following the training and highlight the need for continuation of a program of this nature. PMID- 2245924 TI - An AIDS educational program for third-year medical students. AB - Medical student training now involves an increasing number of patients with HIV infection and AIDS. Thus far educational efforts to change attitudes and behaviors toward AIDS patients have not been successful. Education that only involves the presentation of information appears to be insufficient to alter fearful and prejudicial attitudes toward such patients. Using four different teaching modules (open discussion, role play, and two videotapes) we demonstrated a positive change in students' anticipation of how they would respond to a question or a statement from a non-AIDS patient or a patient with AIDS. There were significant changes in the students' response to AIDS patients on the Understanding, Probing, Focusing, and Judgmental scales of the Medical Helping Relationship Inventory. This initial work suggests that educators can have a positive effect on students' attitudes. Techniques that traverse the emotional barriers students erect to protect themselves from the painful feelings stimulated by working with AIDS appear to be useful. PMID- 2245925 TI - High prevalence of physical illness in a geriatric psychiatric inpatient population. AB - The prevalence of physical illness was determined in a population of geriatric patients on a unit of psychiatric inpatients. Ninety-two percent of the 95 patients were found to have one or more significant medical problems. The average number of medical conditions was 1.9. The disorders were classified according to affected organ system. PMID- 2245926 TI - A case of genital self-amputation in which reconstruction was proposed. PMID- 2245927 TI - [Use of diadynamic currents for analgesia in dentistry. Preliminary note]. AB - In this article the authors have taken in to account the use of diadynamic currents with antalgic aim in odontostomatologic surgery. Based on clinical results in a number of cases, which cannot be analysed statistically due to insufficient number of patients to provide reliable data, the authors conclude that the results obtained justify further research in this field. PMID- 2245928 TI - [Use of NSAIDS in dentistry: double blind controlled study of Diflunisal versus ASA]. AB - As a conclusion to the results obtained during our studies, we can say that both drugs provided fast and accurate antalgic anti-inflammatory characteristics. Diflunisal has however shown a slightly more powerful and larger lasting antalgic action which provides a higher tolerance level than the drug which was used as a comparison. PMID- 2245929 TI - [Needles in dental practice. Clinical evaluation and experiments on deformation and siliconization]. AB - The authors have considered: a) the rate of the deformation of three different needles (Groups B, V, R) when used in different clinical conditions; b) the modification of the surface silicon of the needles after in vivo and in vitro stress. The results have shown a good behaviour of all the groups when employed through the mucous membrane, but a progressively increased deformation after contacts with an osseous surface, significantly higher for groups B and V than group R. No difference in the surface silicon, both among the groups and in relation to the technique of utilization. PMID- 2245930 TI - [Routine measurement of the biggest amniotic fluid pocket in the 3d trimester: prognostic significance?]. AB - The largest pocket of amniotic fluid was measured routinely during the last trimester of pregnancy in 577 patients representing risk and nonrisk cases. The measurements were performed at two clinics between 26 and 42 weeks of gestational age. A statistically significant relationship between a value of less than 30 mm and the following perinatal parameters was found: 5-min Apgar score less than 7, umbilical cord blood pH values less than 7.15, severe neonatal complications, intrauterine growth retardation, perinatal mortality. The good predictive value of decreased amniotic fluid measured by the largest pocket, and the simple practicability of the method raise the question whether the largest pocket of amniotic fluid should not be assessed routinely at each ultrasound examination during the last trimester. The consequences of a decreased value are discussed. PMID- 2245931 TI - [Pseudotumor cerebri in pregnancy]. AB - This is undoubtedly a rather rare clinical picture. The existence of a brain pressure syndrome with symptoms such as headache, increased cerebrospinal fluid pressure, and diplopia simulates a brain tumor, even though the radiological and tomographical evidence is absolutely normal. Therapeutic possibilities are steroid medication, lumbar punctions, as well as a neurosurgical intervention installing a lumboperitoneal drainage. We deem the initial dosage of 16 mg Millicorten/day to be therapeutically effective and adequate. PMID- 2245932 TI - [Premature rupture of the membranes]. PMID- 2245933 TI - [Premature rupture of the membranes in the 2d trimester]. PMID- 2245934 TI - [Vaginal noxae and course of pregnancy]. PMID- 2245935 TI - [Nutrition during pregnancy and the intrauterine development of the fetus]. PMID- 2245936 TI - [Transabdominal and transcervical chorion biopsies. Indications, techniques and current results]. PMID- 2245937 TI - [The diagnosis of infection in pregnancy at risk]. PMID- 2245938 TI - [Fetal anemia]. PMID- 2245939 TI - [Nuclear spin tomography studies in pelvic diagnosis]. PMID- 2245940 TI - [The diagnosis of fetal lung maturity]. PMID- 2245941 TI - [Fetal movement and acoustic stimulation]. PMID- 2245942 TI - [Clinical significance of Doppler flow measurements in fetal blood vessels]. PMID- 2245943 TI - [Maternal blood glucose as screening method for carbohydrate intolerance disorders in pregnancy]. PMID- 2245944 TI - The association of pregnancy-induced hypertension and uterine malformations. AB - To evaluate the incidence of pregnancy-induced hypertension (PIH) in women with congenital uterine malformations, we examined the pregnancy complications of 67 women with uterine anomalies demonstrated by hysterosalpingography (HSG). The study group was compared with a control group of 130 women with normal-shaped uterus proven by HSG-matched for age, parity and presenting complaint. A significantly increased (p less than 0.04) rate of PIH was found for women with uterine malformation as well as a 2-fold higher frequency of preeclampsia. The etiology for this association is unknown, however; it is suggested that uterine malformation is a predisposing condition to PIH. PMID- 2245945 TI - Serum and peritoneal fluid CA-125 levels in early stage endometriosis. AB - Serum and peritoneal fluid (PF) CA-125 levels were assayed using the immunoradiometric assay in 17 women with minimal endometriosis and 21 control women at the time of laparoscopy. Serum levels of CA-125 were not significantly higher in women with minimal endometriosis. Minimal endometriosis was diagnosed with a 70.6% rate of sensitivity and a 71.4% rate of specificity with 16 U/ml as the upper limit of normal. PF CA-125 levels were significantly higher than serum levels but showed no significant difference between control and endometriosis patients. PMID- 2245946 TI - Immunoglobulin contents in cervical secretions of women with chlamydial cervicitis. AB - Contents of albumin, IgG, IgA and secretory IgA (S-IgA) were determined in secretions of 16 women with chlamydial cervicitis (study group) and 13 women with vulvovaginal candidiasis (control group). The amounts of respective protein in cervical secretions were higher among the women with chlamydial infection representing both an increased transudation and an increased local production of antibodies in the infected cervix. Specific chlamydial antibodies of IgG, IgA and S-IgA class were found significantly more often in the study group. Comparing the IgG/IgA ratios in serum and secretions gave indications for an active local secretion of specific IgA antibodies. This was also supported by the demonstration of specific S-IgA. PMID- 2245947 TI - Bacterial vaginosis and the effect of intermittent prophylactic treatment with an acid lactate gel. AB - Intermittent treatment with an acid lactate gel (Lactal, ACO, Sweden) reduced symptoms of bacterial vaginosis (BV) and promoted the reestablishment of the normal vaginal flora of lactobacilli. Forty-two women seriously affected by recurrent BV were initially given acid gel (lactate gel, pH 3.8, 5 ml) to be inserted into the vagina daily for 7 consecutive days. Thereafter they entered into a double blind clinical trial and were treated prophylactically 3 days monthly for 6 months with either lactate gel or a placebo gel. Women treated with the lactate gel were clinically improved, i.e. no signs of BV in 88% compared to 10% in the placebo group (p less than 0.001). The vaginal lactobacilli flora was reestablished in 83% of the lactate group and in 16% of the placebo group. Local intermittent application of lactate gel was found to be free of side effects and is a preferable alternative to repeated treatments with antibiotics in patients with recurrent BV. PMID- 2245948 TI - Short-term maximal electrical stimulation--a conservative treatment of urinary incontinence. AB - Seventeen women with stress and 20 with motor-urge urinary incontinence were treated ambulatorily with short-term maximal electrical stimulation. The duration of the treatment was 20 min daily for 12 weeks. According to the patients' subjective evaluation, two thirds were improved. A markedly diminished leakage of urine (greater than 50% by use of pad test) was found in 6 out of 17 women with stress, and in 13 out of 20 women with motor-urge urinary incontinence. There were no significant differences observed in urodynamic parameters between the registrations performed before and after the present electrical stimulation therapy. PMID- 2245949 TI - Heart rate alterations in a fetus with Ondine's curse. PMID- 2245950 TI - Early development of HELLP syndrome: a case report. AB - The HELLP syndrome is a severe complication of pregnancy. It usually occurs in the middle of the third trimester. In our case, however, a very early development is reported. PMID- 2245951 TI - Discomfort after outpatient abortion using paracervical block: a comparison between two opioids and one non-opioid drug for premedication. AB - One hundred and one patients undergoing outpatient abortion using local anesthesia were randomly allocated to one of three different premedications: morphine-scopolamine, pethidine or midazolam. The incidence of pain, anxiety, emetic (nausea-vomiting) and patient cooperation was analyzed. Discomfort was frequently noticed, 79 patients reported pain, 57 nausea and 26 vomited at least once during the postoperative period which lasted 2.6 h (mean value). There were no major differences in complaints among the different premedication groups. Nausea, though, was correlated to pain. Symptoms of pain, nausea and vomiting were frequent after abortion under paracervical block. These complaints were not found to be related to the type of premedication or other circumstances in the perioperative period. PMID- 2245952 TI - Digoxin-like immunoreactive substance and preterm labor. AB - An endogenous digoxin-like substance (DLIS) that may be related to preterm labor has been studied. Using a commercially available radioimmunoassay kit. DLIS levels were determined in 110 women, of whom 33 were in preterm labor, 27 were in labor at term, 26 had normally ongoing pregnancies before term and were not in labor, and finally 24 were at term but not in labor. Mean DLIS levels of women in preterm labor was found to be significantly high (greater than 0.2 ng/ml, p less than 0.05). Whether this finding points to a causative role for DLIS in preterm labor remains to be further investigated. PMID- 2245953 TI - Serum laminin in pregnancy-induced hypertension--a marker for renal involvement? AB - Laminin, a noncollagenous glycoprotein, has been identified as a component of basement membranes. It serves as a multifunctional adhesion protein. Immunoreactive laminin levels determined by a radioimmunoassay were found to increase throughout gestation, obviously due to growth of the placenta, an organ rich in basement membranes. In this study of 92 pregnant women in the third trimester we compared the serum laminin levels of 69 women with an uneventful course of pregnancy to the levels of 23 women with symptoms of pregnancy-induced hypertension. Laminin concentrations were 2.6 U/ml in pregnant women with hypertension and proteinuria, which was significantly higher than in healthy pregnant women (2.0 U/ml). We supposed that immunologic reactions that damage the kidney account for an increase of laminin concentrations in these women. Therefore we suggest that measurements of serum laminin concentrations may serve as a potential marker of renal damage. PMID- 2245954 TI - Relationship between maternal antithrombin III and protein C/protein S levels before, during and after delivery. AB - The relationship between plasma levels of protein C, protein S and antithrombin III was examined in a group of normal pregnant Chinese women with singleton pregnancies to study the changes in the anticoagulant system in relation to pregnancy, labour and the puerperium. A significant correlation was found between protein C and antithrombin III both before labour and postpartum, and the ratio was close to unity. When the two groups are combined, a highly significant correlation was found (r = 0.758; p less than 0.001). The correlation is not observed at delivery when the ratio becomes very variable and in general greater than unity. The correlation between protein S and antithrombin III was 0.592 before labour and -0.532 at delivery, but both failed to reach statistical significance because of the small numbers. When postpartum concentration of protein C, protein S and antithrombin III is related to interval between sampling and delivery, significant correlation was found only with protein S. The results of this study suggest that the plasma level of protein C and probably protein S is correlated with that of antithrombin III during pregnancy, labour and the puerperium. PMID- 2245955 TI - Comparison between the influence of methylergometrine and oxytocin on the incidence of retained placenta in the third stage of labour. AB - Twenty randomly selected birth centres were questioned about their oxytocic use in the third stage of labour and incidence of retained placenta in relation to the number of vaginal deliveries during 1987. Ten centres used either methylergometrine or oxytocin routinely. Of 6,906 vaginal deliveries treated with 0.2 mg methylergometrine immediately after birth, 187 (2.7%) were complicated by retained placenta. Significantly fewer (p less than 0.001) of the 10,680 vaginal deliveries treated with 5-10 IU oxytocin were complicated by retained placenta (n = 192; 1.8%). PMID- 2245956 TI - [Acute ulcer hemorrhage and current endoscopic hemostatic procedures]. AB - The introduction of diagnostic and therapeutic endoscopy resulted in a drastic decrease in the mortality rates of acutely bleeding ulcer. In addition to thermal coagulation procedures (electrocoagulation, laser, heater probe), injection techniques (adrenaline, ethanol, polidocanol, fibrin adhesive) are available. A combination of initial injection of adrenaline followed by thermocoagulation, or injection of polidocanol, has proved most effective. In the case of fibrin adhesive, applied by non-traumatic means, controlled studies have yet to be performed. The question as to whether, after endoscopic hemostasis, early elective surgery can be obviated in numerous cases, needs to be investigated by controlled prospective studies. PMID- 2245957 TI - [Therapy of bile duct occlusion. Transhepatic/endoscopic "Rendezvous procedure" and percutaneous transhepatic stent placement]. AB - Conversion of a percutaneous transhepatic drainage (PTD) into internal drainage by transhepatic/endoscopic implantation of an endoprosthesis or percutaneous transhepatic implantation of a stent is a relatively simple technique associated with few complications. The advantage of both methods is that they can be performed if endoscopic placement of an endoprosthesis fails, as is often the case in patients with a prior Billroth II procedure or hepaticojejunostomy. Indications, methodology and experience with 29 patients treated with these procedures are described. PMID- 2245958 TI - [First aid against fish poisons. 3: Poisoning caused by fish spines]. PMID- 2245959 TI - [Intrascrotal nongerminal space-occupying lesions]. AB - Four to ten percent of testicular cancers are shown histologically to originate from non-germinal cells. Benign lesions and extratesticular intrascrotal tumors may be confused clinically with germinal cell testicular cancer. Incidence, diagnosis and therapy of intrascrotal non-germinal cell tumors are discussed in this publication. PMID- 2245960 TI - [Prostaglandin E1 injection in erectile dysfunction. Current diagnostic and therapeutic possibilities]. AB - In erectile dysfunction formerly, for both diagnostic and therapeutic purposes, intracavernous injections of papaverine and the combination papaverine/phentolamine were employed. In recent years, promising results have been reported with prostaglandin E1. In a multicenter study, 10 to 20 micrograms prostaglandin E1 were administered for testing corpus cavernosum function. One hundred and fifteen out of 187 patients self-injected themselves with prostaglandin E1 at an average dose of about 13 micrograms. While priapism occurred in 5 to 10% of the patients injecting papaverine or papaverine/phentolamine, and fibrosis and tunica induration in 10 to 57% patients on long-term treatment, the risk of priapism was low in prostaglandin E1. Subsequently, induration and penile deviation were reported in 2 patients each. In this multicenter study, a subjective efficacy of more than 90% was observed, thus confirming similar results with prostaglandin E1 found in other studies. The present results show that prostaglandin E1 can be considered the drug of first choice for intracavernous injection treatment of erectile dysfunction. PMID- 2245961 TI - [MPPG complex belongs in the first phase of drug-assisted lipid lowering (magnesium-pyridoxal-phosphate-glutamate )]. PMID- 2245962 TI - [Why does adequate tolerance of a lipid-lowering agent play such an important role?]. PMID- 2245963 TI - The Seville hGH Symposium. Clinical aspects of growth hormone replacement therapy. Seville, Spain, April 18-21, 1990. Proceedings. PMID- 2245964 TI - Assessment of growth hormone secretion: what are we looking for practically? AB - GH is a dominant factor in determining growth during childhood. Hence, the assessment of GH secretion is of major importance in the diagnosis of growth disorders. Since GH is secreted in a pulsatile fashion, a truly accurate production rate can only be calculated by using very frequent or continuous blood sampling over a 24-hour period. Several standard provocative tests have been established to evaluate GH secretory status. They remain the cornerstone in the assessment. Recent data have shown the existence of a wide spectrum of GH secretory disturbances ranging from severe GH deficiency to partial insufficiency and neurosecretory dysfunction. There is no well-defined cut-off point at which a particular child can be regarded as GH insufficient or sufficient for optimal growth. In clinical practice, the assessment of GH secretion starts with the careful analysis of the growth chart and height velocity. Careful clinical examination of the patient is essential for the proper diagnosis, and to exclude diseases influencing GH secretion. Additional biochemical tests may be required for the differential diagnosis. Thus, assessment of GH secretion in children requires auxological, clinical and biochemical data. GH insufficiency is documented by additional testing of pituitary secretory capacity either by standard provocative tests, by studying 24-hour GH profile or by measuring 24 hour production rate. The main goal is to detect those children who will benefit from treatment with hGH. The final assessment might consist in the response of growth velocity to exogenous hGH. PMID- 2245965 TI - Measurement of urinary growth hormone. A noninvasive method to assess the 'growth hormone status'. AB - Using pharmacological tests or GH profiles, GH deficiency or active acromegaly can be diagnosed. However, it is impossible to discriminate within the continuum between 'deficiency/insufficiency' and 'sufficient secretion'. The use of GH to improve growth velocity is based on 1 injection once a day. It is thus the total amount of GH which appears to be important for its growth-promoting effect. An assay of GH in urine allows to assess such GH 'production', even over a prolonged period of time. A radiometric two-step assay applicable to untreated urine is presented. Results for assessing the 'GH status' by measuring GH in 24-hour urine, first morning-void urine or timed urine samples are shown. The correlation between 24-hour plasma profiles and the simultaneously collected 24-hour urine is significant at p less than 0.01. A correlation coefficient greater than 0.9 was found between timed urine samples (4 h) and the 120-min plasma GH values during GHRH stimulation tests. The night-to-night variation of urinary GH can be very important. It is advisable, therefore, to use the mean of several night urines. The correlation between the mean urinary GH of 5 nights to one 24-hour sample is significant at p less than 0.01. An age-dependent increase in urinary GH is found in the pubertal age group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245966 TI - Growth hormone and body composition. AB - Through its anabolic, lipolytic and antinatriuretic actions, GH has profound effects on body composition. In untreated acromegaly, body weight, body cell mass and extracellular water are increased simultaneously with a decrease of body fat. After successful treatment, extracellular water and body fat normalize, but cell mass remains high. The changes in cell mass, body fat and extracellular water observed in acromegaly suggest different dose-response relationships between GH and these parameters. The relationship between GH concentration and the lipolytic actions of GH is more linear, while the relationship between GH and excess extracellular water is more curvilinear. The sodium-retaining effect of GH seems to be mediated by stimulation of the Na(+)-K+ pump. At higher GH levels, the pump activity is counteracted by an alleged sodium transport inhibitor. In GH deficient children, GH treatment is followed by rapid loss of adipose tissue and muscular gain. The influence of GH on body composition in GH-deficient adults has recently received attention. Compared to normal subjects, these patients are overweight and have decreased cell mass. Replacement treatment with GH restores body composition towards normal. PMID- 2245967 TI - Insulin-like growth factor measurements in the evaluation of growth hormone secretion. AB - The measurement of circulating levels of the insulin-like growth factors (IGF-I and IGF-II) in the evaluation of GH secretion is discussed. GH is an important regulator of circulating IGF-I levels in humans. Circulating IGF-I levels are low in patients with GH deficiency, elevated in those with GH excess, and correlated well with physiologic changes in GH secretion. The levels also increase in response to administration of exogenous GH or GH-releasing hormone. However, IGF I levels are age dependent and subject to regulation by other hormones and nutritional variables; these features complicate the interpretation of IGF-I levels in individual patients and limit the usefulness of these measurements, particularly for determining GH deficiency in young children. Circulating IGF-II levels are not GH dependent and, therefore, their measurement is of little clinical utility in assessing GH secretion. PMID- 2245968 TI - Psychological well-being before and after growth hormone treatment in adults with growth hormone deficiency. AB - The effect of recombinant-DNA human growth hormone treatment on psychological well-being and quality of life was studied in adults with GH deficiency (GHD). 24 adults who satisfied strict criteria for GHD took part in a double-blind, placebo controlled, 6-month trial. Quality of life assessments were performed at entry, 1 and 6 months by means of self-rating questionnaires. This study reports significantly lower scores on quality of life assessment in the GH-deficient patients at entry compared with matched controls, indicating that this population may be psychologically compromised. Preliminary analysis of treatment results shows that after 6 months, those patients receiving active treatment experienced less perceived illness than the placebo group. Significant psychological improvements were noted in the patients' perception of their energy level and mood. PMID- 2245969 TI - Skeletal muscle performance in adults with growth hormone deficiency. AB - Skeletal muscle mass and function were assessed in 24 adults (16 males, 8 females) with severe, long-standing GH deficiency. Compared to 41 untrained controls (26 males, 15 females), adults with GH deficiency had reduced cross sectional area of thigh muscle/body weight (p = 0.01), reduced quadriceps force/weight (males: p = 0.002; females: p less than 0.0001), and reduced quadriceps force/muscle area (males: p = 0.005). This suggests (a) that adults with GH deficiency have reduced skeletal muscle mass due, in part, to the absence of the anabolic effects of GH, and (b) that skeletal muscle force may be reduced due to altered muscle mass, contractile elements/muscle fibre, anaerobic energy supply, neural recruitment of fibres, or a combination of these. PMID- 2245970 TI - Effects of growth hormone on body composition in adults. AB - GH replacement therapy in GH-deficient adults has recently been shown to increase (normalize) muscle volume and decrease adipose tissue volume as measured by means of CT scan and skinfold thickness. Also in adults with acquired GH deficiency in adulthood, GH replacement has been shown to significantly influence body composition with an increase in lean body mass and a reduction in skinfold thickness. Preliminary results from an open long-term trial indicate that 12 months of GH substitution result in a further normalization of the muscle/fat ratio. The fluid-retaining effect, with a significant increase in extracellular fluid volume demonstrated during GH administration to normal subjects, seems to be of little clinical importance if a replacement dose around 2 IU/m2/day is chosen for young GH-deficient adults. Long-term trials are needed to finally establish the indication of GH replacement therapy in GH-deficient adults. PMID- 2245971 TI - Growth hormone (replacement) therapy in adults: bone and calcium metabolism. AB - Calcium uptake from the gut is increased by GH effects on vitamin D metabolism or action. Bone metabolism is stimulated by many factors, of which GH and insulin like growth factor I (IGF-I) are only two examples. From various animal and human data, it can be shown that GH and IGF-I seem to influence bone formation more than bone resorption. However, GH excess, as seen in acromegaly, does not result in increased bone mass. GH was used to treat osteoporosis in a few clinical trials. In only one, in combination with calcitonin, an increase in bone mass was observed. In GH-deficient adult patients, substitution therapy resulted in a temporary increase in serum calcium levels. Effects on bone mineral mass were only found in a pilot study performed by us in a group of 8 GH-deficient adult patients. The mean increase of bone mineral mass was 0.04 g hydroxyapatite/cm2, p less than 0.05. These data indicate that GH substitution can result in increased bone mass. PMID- 2245972 TI - Results of long-term growth hormone replacement therapy in children: when and how to treat? AB - Up to now, the end results of treatment in GH deficiency (GHD) have not been as good as expected. Probably the main cause has been the delay in diagnosing GHD in short children, resulting in a very insufficient height at the onset of puberty. The need for early diagnosis and treatment must be emphasized. This agrees with the well-documented data demonstrating (1) that catch-up growth obtained in any treatable growth disorder has a limited duration, and (2) that the effect of GH replacement, whatever the doses and modes of therapy, is maximal during the first year and wanes during the following years. There are still many questions regarding the appropriate GH replacement dose. The height gain during the first year of treatment has been correlated with the logarithm (decimal or natural) of the dose in several groups of patients receiving GH 3 times/week. The initial dose-response relationship is better with GH 6 times/week. For the following years, no dose/response ratio has been demonstrated, and the final height-to-dose relations are still to be investigated. A dose increase after 2 years or more may improve the growth rate, but also with secondary waning. Thus, long-term prospective dose-response studies are needed. The first period of one such study is presented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245973 TI - Secretory patterns of growth hormone according to sex and age. AB - Gender and age have distinct and interrelated effects on GH secretion in adults. GH secretion falls significantly with aging, particularly in women. The fall in GH release is amplitude- rather than frequency-modulated and appears to be related to estrogen status. Oral estrogen administration is unphysiological and causes a marked perturbation of the GH/insulin-like growth factor I axis. A nonparenteral route of administration is required for further investigations of the physiological role of estrogen in GH secretion. PMID- 2245974 TI - Pharmacological aspects of growth hormone replacement therapy: route, frequency and timing of administration. AB - Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH injections revealed no side effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2245975 TI - Frequency of administration of growth hormone--an important factor in determining growth response to exogenous growth hormone. AB - Growth hormone (GH) secretion in man occurs in a pulsatile manner with a dominant periodicity of 200 min. Animal studies and growth hormone-releasing hormone therapeutic studies in man demonstrate the importance of the frequency of GH pulses on the growth response observed. Daily injections of GH produce effective growth. More frequent regimens may be beneficial to prevent waining of the growth spurt induced by GH therapy. PMID- 2245976 TI - Growth hormone treatment in patients with neurosecretory dysfunction. AB - Twenty-four children (14 boys and 10 girls) with neurosecretory dysfunction, defined by a response greater than 10 ng/ml to two pharmacological tests, and 24 hour GH secretion less than 3 ng/ml/min, were treated with biosynthetic hGH. Mean age was 10 years 8 months +/- 3 years 6 months. Growth retardation was -2.8 +/- 0.8 SD. Eighteen children were prepubertal and six pubertal (P2). Mean peaks in two pharmacological stimulation tests were 25.8 +/- 14.8 and 20.8 +/- 11.5 ng/ml. Somatomedin C/insulin-like growth factor I level was 0.8 +/- 0.6 IU/ml in the prepubertal children. Twenty-four-hour integrated concentration of GH was low, at 2.2 +/- 0.5 ng/ml/min. Analysis of secretory profiles showed 3 types: (1) hyperpulsatile profile with numerous peaks of low amplitude, (2) flat profile, (3) profile with an isolated peak greater than 10 ng/ml. Treatment with hGH (0.42 IU/kg/week) resulted in an increase in growth velocity from 4.9 +/- 1.2 to 6.8 +/ 2.2 cm/year. These results are comparable to those of a group with total GH deficiency receiving the same dose. Analysis of the results showed a group of good responders (n = 14, growth velocity: 8.1 cm/year) and a group of poor responders (n = 10, growth velocity: 4.9 cm/year). Thus, treatment of neurosecretory dysfunction with hGH gives results comparable to those obtained in classic GH secretory dysfunction. PMID- 2245978 TI - Epidemiology and aetiology of acute non-tuberculous salpingitis. A comparison between the early 1970s and the early 1980s with special reference to gonorrhoea and use of intrauterine contraceptive device. AB - More patients were hospitalised for acute salpingitis at the Department of Obstetrics and Gynaecology, Orebro Medical Centre, Orebro, Sweden, during the 5 year period 1970-1974 (period I) as compared with that of 1980-1984 (period II), 666 patients and 524 respectively, a decrease of 22%. The majority of cases, 92% in period I and 85% in period II, occurred among women 15-34 years of age, that is a relative increase of patients aged over 34 from 8% in period I to 15% in period II. Concomitant urogenital gonorrhoea occurred in 26.2% of the patients in period I compared with 12.0% in period II, a highly significant decrease (p less than 0.001) mainly confined to the age group 15-24, whereas there was no relative difference for the two periods in the age group 25-34 years. The number of patients using intrauterine contraceptive device (IUCD) was 96/666 (14.4%) in period I compared with 113/524 (21.6%) in period II (p less than 0.001). There were also relatively more IUCD users among the patients with gonorrhoea and acute salpingitis in period II (15.5%) compared with period I (10.4%) but this difference was not statistically significant. From 1981 to 1984 370/424 patients were cultured for Chlamydia trachomatis and 27.8% (103/370) were positive. Thus Chlamydia trachomatis is at present, at least in the Orebro area, the most frequently isolated STD agent among acute salpingitis patients while gonorrhoea is of much less importance. PMID- 2245977 TI - Molecular techniques in the diagnosis of human infectious diseases. PMID- 2245979 TI - Herpes simplex virus type 2 and other genital ulcerative infections as a risk factor for HIV-1 acquisition. AB - We studied the role of genital ulcerative infections for acquisition of human immunodeficiency virus type 1 (HIV-1) infection in a cohort of 989 homosexual men in Amsterdam between October 1984 and December 1988. Among 53 HIV-1 seroconverters serological and anamnestic data were gathered regarding herpes simplex virus type 2 (HSV-2) and syphilis in the 6 months before seroconversion. For statistical analysis a control who remained seronegative during the same interval was selected at random for each HIV-1 seroconverter. A significant difference between the prevalence of HSV-2 antibodies among HIV-1 seroconverters and controls was found (72% vs 38%). HSV-2 seroconversions among men initially seronegative for HSV-2 were found among three of 18 HIV-1 seroconverters and among three of 36 controls. (O.R. = 2.2, 95% C.I. 0.4-12.1). Self-reported cases of anogenital herpes were found more frequently among HIV-1 seroconverters (8) than among controls (4). One case of syphilis was diagnosed among HIV-1 seroconverters, and one among controls. Summing up these cases we assessed the total number of genital ulcerative infections: 12 among HIV-1 seroconverters and eight among controls (23 vs 15%, O.R. 1.7, C.I. 0.6-4.62). These data suggest little evidence for genital ulcerative infections being an important independent risk factor for HIV-1 acquisition among homosexual men in Amsterdam during the time period studied. PMID- 2245980 TI - The prevalence of sexually transmitted diseases among prostitutes in Malaysia. AB - The prevalence of sexually transmitted diseases was determined among 370 prostitutes in Kuala Lumpur, Malaysia. Chlamydial cervicitis (26.5%) was detected more frequently than gonorrhoea (14.25%) and was associated more often with pelvic inflammatory disease. Concurrent infections and asymptomatic infections were common. Seropositivity to hepatitis B and syphilis were 66.3% and 13.6% respectively. Women under 20 years of age had significantly higher rates of infection with Chlamydia trachomatis and hepatitis B virus than older women. PMID- 2245981 TI - Human immunodeficiency virus (HIV) infection, sexually transmitted diseases and HIV-antibody testing practices in Belgian prostitutes. AB - From December 1988 to April 1989, 154 female prostitutes in and around Ghent, Belgium, were interviewed about their knowledge, attitudes and practices in relation to the risks for sexually transmitted diseases (STD) and human immunodeficiency virus (HIV) infection in their profession. Thirty four women worked as window prostitutes, 120 picked up their clients in bars, clubs, and saunas. Blood samples were taken from 123 women. One (0.8%) was seropositive for HIV1, 19 (15.4%) had Hepatitis B core antibodies (anti-HBc), eight (6.4%) showed markers of syphilis. None of them were Hepatitis B surface antigen (HBsAg) carriers. Hepatitis C antibodies (anti-HCV) were present in the serum of three women (2.4%). Overall STD seroprevalence was higher in the group of window prostitutes than in the group of club prostitutes. One woman admitted intravenous drug use. Former testing for anti-HIV antibodies had been performed in 102 (66.5%) respondents, of whom 84 (82.3%) were tested in the year preceding the interview. In 74.5% of the cases, these tests were requested by the women themselves. These results suggest that HIV infection is not yet prevalent in non intravenous drug using prostitutes in Ghent, but that this situation may change considering their higher rates of past STD. Window prostitutes are at higher risk than club prostitutes. Testing for HIV seems to be common practice, mostly at the request of the women themselves. Health education should discourage the notion of testing as an alternative to using condoms. PMID- 2245982 TI - Factors influencing condom use in a sample of homosexually active men. AB - A sample of 502 homosexually active men were recruited from genitourinary medicine clinics and non clinic sources and interviewed in relation to their sexual behaviour and factors that might influence their use of condoms. Three hundred and eighty three men (76%) reported penetrative anal sex in the previous year. Ninety four (25%) had not used condoms in penetrative sex. Failure to use condoms was associated with unfavourable attitudes to them, not knowing close friends or partners who had HIV-related health problems, having fewer sexual partners and being in a closed monogamous relationship. On the other hand levels of awareness about the risks of unprotected anal sex and involvement in gay networks and social groups were not predictors of condom use. PMID- 2245983 TI - Intermittent prophylactic treatment of recurrent vaginal candidiasis by postmenstrual application of a 500 mg clotrimazole vaginal tablet. AB - The therapeutic efficacy of intermittent, monthly, postmenstrual prophylaxis with a single 500 mg clotrimazole vaginal tablet (n = 33) was compared with placebo tablets (n = 29) in 62 woman (age 28.1, SD 7.2 years) with recurrent vulvovaginal candidiasis. The number of episodes of acute vulvovaginal candidiasis experienced during the year prior to inclusion was 6.3, SD 1.9. The cumulative recurrence frequency after 6 months intermittent prophylaxis with clotrimazole (30.3%) was lower (p less than 0.001) than that recorded for the women who received placebo (79.3%). After an additional 6 months observation period without treatment there was no significant difference in the cumulative recurrence frequency between the groups (clotrimazole 84.9%; placebo 86.2%). The vagina was recolonised with Candida albicans in 70% of the women after 6 months prophylactic treatment with clotrimazole and in 86% of the women who had received placebo. Thus, this study has demonstrated that postmenstrual prophylactic treatment with a single 500 mg clotrimazole vaginal tablet, applied monthly, prevents recurrence of symptoms, although it does not eliminate yeasts from the vagina. PMID- 2245984 TI - Screening for cervical Chlamydia trachomatis infections in two Dutch populations. AB - Endocervical cultures for Chlamydia trachomatis and Neisseria gonorrhoeae were taken from 492 women attending an outpatient clinic for sexually transmitted diseases (group I) and 560 women seeking legal abortion (group II). Possible risk factors for C trachomatis infection were evaluated by multivariate analysis. The prevalence rates for C trachomatis and N gonorrhoeae were 7.3% and 2.5% in group I and 9.4% and 0.4% in group II. From multivariate analysis it was found that age (p less than 0.01), number of sexual partners (p less than 0.01), abnormal vaginal discharge (p less than 0.01), and endocervical mucopus (p = 0.02) were independently associated with chlamydial infection in group I. In the abortion clinic age (p = 0.03) and endocervical mucopus (p = 0.03) were the only significant independent predictors of C trachomatis. In all women vaginal discharge was collected for Gram staining. A significant higher number of polymorphonuclear cells was seen in the smears of C trachomatis positive women (group I: p = 0.04; group II: p = 0.03). In group II there was also a significant association between C trachomatis and Gardnerella type bacterial flora (p = 0.02) and the presence of comma-shaped rods (p = 0.04). Screening for C trachomatis infection may help to decrease the incidence of (post-abortal) pelvic inflammatory disease. Because screening in abortion clinics is not always possible, decreasing the incidence of postabortal pelvic inflammatory disease could be achieved by using prophylactic antibiotics. Selective use of prophylaxis in high risk patients can minimise costs and the incidence of side effects. PMID- 2245985 TI - Gummatous lesions in men infected with human immunodeficiency virus and syphilis. AB - Two HIV-infected men are reported who developed gummatous lesions more than 12 months after appropriate treatment of presumptive syphilis. In one patient the lesions developed without any change in the VDRL titre. The most likely explanation for these lesions is reactivation of syphilis in the context of HIV infection. As these lesions respond to penicillin, the possible reactivation of appropriately treated syphilis, or even yaws, should now be considered in any ulcerative lesion in HIV infected individuals at risk from treponemal infection. PMID- 2245986 TI - Granuloma inguinale of the cervix: a carcinoma look-alike. AB - Granuloma inguinale of the cervix presents as a proliferative growth and may mimic carcinoma. Over a 3 year period 18 patients with cervical granuloma inguinale were detected. Nine (50%) had a clinical diagnosis of carcinoma of the cervix on admission, five of whom had extensive investigations to exclude a malignancy. In communities where these two conditions are commonly seen it is recommended that granuloma inguinale be considered in young women with granulomatous lesions of the cervix, so as to avoid extensive and financially costly investigations, and unnecessary psychological stress for patients. PMID- 2245987 TI - Sexually transmitted diseases in Italy: clinical returns versus statutory notifications. AB - Sexually Transmitted Diseases (STD) surveillance has caught the attention of the Italian public health authorities during the past decades. The spread of HIV infection increased the awareness of the need for a better STD surveillance system. This paper reports a retrospective survey of STD clinics in Italy, intended to form an epidemiological base for further development of STD surveillance. The data for 1986-87 and 1988 on a predefined set of diseases, all of them sexually transmitted, were collected from 85 of 127 centres contacted. The data obtained offer the first national figures for some STD not included in the statutory notification list, such as chlamydial infection, herpes and genital warts, as well as HIV infections. Those data show an increase in time frequencies. For gonorrhoea and syphilis, it was possible to compare our data with statutory notifications, showing a large gap between notified and reported cases. This gap is not stable in time (increasing in time) or in geographical area (increasing from north to south). PMID- 2245988 TI - Survey of human immunodeficiency virus infection and sexually transmitted diseases in homosexual and bisexual men attending genitourinary medicine clinics in the UK during 1986-88. The British Cooperative Clinical Group. AB - A multicentre investigation was made into the prevalence of sexually transmitted diseases and HIV infection amongst homosexual/bisexual (HS/BS) men attending genitourinary medicine clinics in the UK during the final quarters of 1986, 1987, and 1988. The results from individual clinics have been collated into regional groupings in order to assess geographical and temporal trends. A statistical analysis has also been performed on the data from 19 large teaching hospital clinics which contributed to both the 1986 and 1988 studies. There was a marked decline in the numbers of HS/BS men attending clinics and a statistically significant decrease in the prevalence of infectious syphilis and gonorrhoea. Although there was a concomitant fall in HIV testing rates, the prevalence of newly detected HIV antibody positive patients remained virtually constant. In 1988, 12.2% of 544 HS/BS men attending clinics in the Thames regions compared with 5.9% of 895 attending clinics elsewhere in the UK were found to be seropositive. No less than 30% of the 122 newly diagnosed individuals had been seronegative at a previous test during 1987/88. In addition to these new diagnoses, there were 953 attenders who had been previously diagnosed as being HIV seropositive. Total HIV seropositivity rates amongst HS/BS attenders ranged from 15-29% in different regions. These overall figures may underestimate the true size of the seropositive HS/BS clinic population because of the large number of untested individuals which constituted 33-51% of clinic attenders. The proportion of seropositives with clinical manifestations of chronic HIV infection was 54% nationally and was highest in the Thames regions and lowest in North England. Despite changes in the sexual behaviour of HS/BS men in the UK during the mid-eighties, a large proportion have been infected with HIV which has become the most widespread and prevalent sexually transmitted disease in patients attending genitourinary medicine clinics. PMID- 2245989 TI - Guidance for the planning and design of genitourinary medicine clinics. AB - The number of patients attending genitourinary medicine (GUM) clinics in Britain has risen greatly in recent years. In contrast there have been very modest increases in staff and there are no data on accommodation or facilities. The Department of Health therefore set up a team to provide guidance on the planning and design of GUM clinics. After a survey the team concluded that GUM clinics in England were poorly and inappropriately accommodated. In their guidance they recommended that GUM clinics are sited in general outpatient departments (OPDs) of general hospitals; this improves patient care simplifying cross referral, consultation and other aspects of operational efficiency and convenience for patients, improves cost effectiveness and increases convenience for staff. Some facilities may be shared. Reception should be an attractive focal point and allow patients to be received and registered in privacy. Facilities for clinical examination are the central part of a clinic. Rooms which allow consultation and examination (CE) rooms of male and female patients maximise efficiency, flexibility and confidentiality. Sound attenuation is vital and decor should be attractive so inspiring confidence by producing a non-institutional atmosphere. An adequate number of CE rooms is essential and the waiting area should be sufficient for booked and walk in patients plus companions. There must be rooms for venepuncture, treatment and colposcopy. Interviewing rooms and offices are important, and there must be a secure health records store. A childrens play area and staff accommodation can be shared. An area for handling and simple investigation of patients' specimens is essential. This guidance should be interpreted flexibly. Though commissioned by the Department of Health for England, it is hoped that it will be useful for planning and designing genitourinary medicine clinics throughout Britain and in other countries. PMID- 2245990 TI - Eminent venereologists 4: Jonathan Hutchinson. PMID- 2245991 TI - Detection of Chlamydia trachomatis in semen samples. PMID- 2245992 TI - Value of performing biopsies in genitourinary clinics. PMID- 2245993 TI - Outpatient treatment of syphilis with penicillins. PMID- 2245994 TI - Post-gonococcal urethritis: a double blind study of doxycycline. PMID- 2245995 TI - Recurrent genital tract infections: a result of induced immunosuppression. PMID- 2245996 TI - Therapeutic update of eczema and topical corticosteroids. PMID- 2245997 TI - Topical urea in dermatology. AB - For years research has been conducted to find a cutaneous moisturizer that is effective, easily available and relatively inexpensive urea, as a atopical agent, is all of this and is also a mild keratolytic. A trial was conducted over 200 patients suffering from a variety of disorders that were selected and using urea topically as urea 10 (10%), urea-20 lotion (20%), Urea-HC (with hydrocartisanl). The agent was applied twice daily for a maximum period of 8 weeks. Results indicate that urea is an effective moisturizer and in promotes the penetration of hydrocelisone into the skin. PMID- 2245998 TI - Therapeutic update: viral dermatosis and AIDS. PMID- 2245999 TI - Problems in the management of superficial mycoses. PMID- 2246000 TI - An update in the therapy of psoriasis. PMID- 2246001 TI - Therapeutic update of common STDs. PMID- 2246002 TI - Therapeutic update of pigmentary disorders. PMID- 2246003 TI - Therapeutic update: leprosy and it's reactions. PMID- 2246005 TI - Differentiating causes of chest pain. PMID- 2246004 TI - Evaluation of electron beam irradiation technique in Indian breast carcinoma patients. AB - A technique for post-mastectomy irradiation in breast cancer patients is described. The chest wall and internal mammary nodes are irradiated with single, anterior electron beam. The axillary and supraclavicular nodal regions are treated with parallel opposed telecobalt beams. A total of 124 patients have been subjected to this procedure. All, except five, completed the treatment. Desquamation, dry as well as wet, was of universal occurrence in electron irradiated zones. The follow up period is 2-26 months with a median of 12 months. Out of the 106 followed up patients, two developed local recurrence while distant metastases were observed in 13 patients. PMID- 2246006 TI - Serum zinc and zinc containing enzymes in diabetes mellitus. AB - Serum zinc and levels of certain zinc containing enzymes like 'lactate dehydrogenase, malate dehydrogenase, alkaline phosphatase and serum insulin were studied in twenty five normal and fifty non insulin dependent diabetics. Zinc estimation was done bp atomic absorption spectrophotometry, insulin by radioimmunoassay and the enzymes by kinetic method. The non insulin dependent diabetic individuals showed significant hypozincaemia (P less than 0.001) associated with significant increase in serum insulin and lactate dehydrogenase level (P less than 0.001). Malate dehydrogenase level was markedly decreased (P less than 0.001). There was no significant variation in serum total proteins, creatinine and alkaline phosphatase levels. PMID- 2246007 TI - Skeletal metastases in carcinoma of the uterine cervix--a report of two cases and review of literature. AB - Occurrence of skeletal metastases in carcinoma of uterine cervix is infrequent. There are only a few cases who present wits osseous involvement at the time of initial diagnosis. Appearance of skeletal metastases in carcinoma uterine cervix is an ominous sign of progression of disease. Screening studies for detection of occult skeletal metastases in asymptomatic patients are not recommended. PMID- 2246008 TI - Neonatal/perinatal medicine training program in USA. PMID- 2246009 TI - Training in neonatology in India. PMID- 2246010 TI - Nutritional modulation of phagocyte function with special emphasis on the newborn. PMID- 2246011 TI - Lower airway obstruction in the PICU. AB - Lower airway obstruction is one of the most frequent causes of admission to pediatric intensive care unit. A thorough understanding of the pathophysiology underlying the disease will lead to effective management and decreased mortality and morbidity. PMID- 2246012 TI - Non-invasive monitoring in the pediatric ICU, Part I: Transcutaneous oxygen monitoring (PtcO2). PMID- 2246013 TI - Non-invasive monitoring in the pediatric ICU, Part III: Pulse oximeter. PMID- 2246014 TI - Evaluation of national nutritional anemia prophylaxis programme. AB - An evaluation of the National Nutritional Anemia Prophylaxis Program was carried out in Andhra Pradesh. About 8,000 respondents from about 5,754 households were interviewed and 487 pregnant women were covered for haemoglobin estimation in six selected districts. Nearly 19 per cent of the pregnant women had received folifer tablets, while about 1 per cent of child beneficiaries were receiving the tablets. The acceptance of the programme by the community appeared to be satisfactory. The reasons for poor coverage were reported to be inadequate and irregular supplies. Results indicated that the health functionaries were not properly oriented towards the programme, as many of them were not aware of all the beneficiaries under the programme. Chemical analysis of the tablets indicated that about 30 per cent of the tablet samples had iron content less than the expected levels, and none of them had expected levels of folic acid content. PMID- 2246015 TI - Feeding of colostrum in urban and rural areas. AB - The practice of colostrum feeding and factors influencing the same were studied by interviewing 2158 mothers belonging to low socio-economic group from urban slums and rural areas of Maharashtra and Gujarat. Statistically significant (p less than 0.001) difference was found between rural and urban areas with regard to the practice of feeding colostrum. Though the percentage feeding colostrum was very poor, the discard of colostrum was very less among rural mothers. Developmental programmes such as ICDS and others also showed significantly beneficial effects on colostrum feeding practice in both urban and rural (p less than 0.001) areas. Socio-economic factors such as better income (p less than 0.001) and hospital delivery were noted to have positive influence on colostrum feeding. Religion did not seem to affect the practice of colostrum feeding. PMID- 2246016 TI - Evaluation of vaccination coverage. AB - The cluster sampling methodology based on WHO module on "Evaluate Vaccination Coverage" recommended by Ministry of Health and Family Welfare, Government of India, 1987 was followed to evaluate the vaccination coverage of eligibles. Out of the 215 eligible children between 12-23 months of age, 44.65 38.61 and 16.74 per cent were found to be fully, partially and unimmunized respectively. The dropout rate for OPV and DPT was 21.23 while it was 4.03 per cent for TT. Based on the studied facts responsible for non or partial immunization, suggestions have been made to accelerate the coverage and reduce the dropout rate. PMID- 2246017 TI - Circulating immune complexes in tuberculosis--an indicator of activity. AB - Circulating immune complexes (CIC) were assayed in 100 cases of tuberculosis and 30 age matched control children. The estimation was done by PEG assay before the commencement of antitubercular therapy. CIC were present in only 3.3% of the control children as compared to 68% of children with tuberculosis. The presence of CIC was observed to vary with the type of tuberculosis. The percentage positivity was highest (100%) in children with miliary tuberculosis. Subsequent estimation of CIC done after one and three months of antitubercular therapy showed a marked decrease in the percentage of positive cases (6.1 and zero percent respectively). PMID- 2246018 TI - Cell mediated immunity in childhood malaria. AB - Children with malarial infection, due to P. Vivax and P. falciparum, were tested for cell mediated immunity (CMI) by lymphocyte proliferative response to mitogens PHA (phytohaemagglutinin) and PWM (poke weed mitogen) and antigen PPD (purified protein derivative). This was done during the period of parasitemia and after treatment, and compared to 19 normal matched controls. There was no significant difference between the patients and the control group with regard to PHA (patients 57.4 +/- 50.5; controls 61.3 +/- 54.9); PWM (patients 27.4 +/- 19.9, controls 29.9 +/- 24.5); PPD (patients 2.2 +/- 1.2, controls 1.9 +/- 1.4). There was also no significant difference in the lymphocyte responses during the period of parasitemia and after treatment. Hence, there does not seem to be any depression of CMI as shown by lymphocyte proliferative responses during childhood malaria. PMID- 2246019 TI - Temperament characteristics of mentally retarded children. AB - In a comparative study of temperament and intelligence in groups of mentally retarded and normal children, it was found that mentally retarded children who also had excess of psychopathology in them, showed greater signs of 'difficult' child temperament. Relationship between intelligence and emotionality variable of temperament was linear and positive in the mentally retarded children. This study generates the hypothesis that negative mood may be temperamental correlated with mental retardation. PMID- 2246020 TI - Pectus excavatum in children: diagnostic significance for mitral valve prolapse. AB - Eighty-seven patients with pectus excavatum underwent cardiac examination and echocardiography (M-mode) to determine the diagnostic significance of pectus in children for mitral valve prolapse (MVP). Patients' ages ranged from 1 month to 18 years with a mean age of 5.4 years. Sixty-seven were males. Twenty of the 87 pectus patients (23%) had echocardiographic evidence of MVP, whereas 11 of these had auscultatory findings of a non-ejection click or late systolic murmur, and 4 had significant mitral insufficiency. Fourteen of the 77 patients (18%) with mild pectus, and 6 of the 10 patients (60%) with severe pectus had MVP. Two of the patients (3.4%) with mild pectus and 2 of the patients (20%) with severe pectus also had significant mitral insufficiency. Ten of the 23 patients (44%) older than 8 years of age and 10 of the 64 younger patients (16%) had MVP. Although MVP was present more frequently in females (30%) than in males (21%), the difference was not statistically significant. This study indicates the high incidence of MVP in children of 8 years of age and older, especially when pectus deformity is severe. This information is particularly helpful to heighten suspicion of MVP in children with pectus excavatum. PMID- 2246021 TI - Emergency management of the acutely poisoned child/adolescent. PMID- 2246022 TI - Cytogenetic studies in a population suspected to have chromosomal abnormalities. AB - The present study describes the cytogenetic findings in cases suspected with chromosomal abnormalities, in cases of mental retardation, multiple congenital malformations, clinical features of Down's syndrome, Klinefelter's syndrome, Turner's syndrome, ambiguous sex, sterility, amenorrhea and history of repeated spontaneous abortions in couples. Cytogenetic studies were done in 144 of the total 205 cases. In all, 57 (39.58%) were shown to have chromosomal abnormality and of these, 34 cases (25.7%) were Down's syndrome. Sex chromosome abnormality was found in 19 cases (13.2%). The results confirm the significant contribution of chromosomal abnormalities in the genesis of mental retardation, and abnormal sexual development. PMID- 2246023 TI - Familial fragile secondary constriction on chromosome 2 (2q11) with unusual features and psychomotor retardation. AB - A child with fragile secondary constriction 2q11 associated with unusual clinical features and psychomotor retardation is described. The pathogenetic significance of this fragile site still remains unclear, and heterogeneity of clinical manifestations is not well understood. PMID- 2246024 TI - Use of Foley catheter in the removal of marble from the esophagus. PMID- 2246025 TI - Bilateral double patellae. PMID- 2246026 TI - Importance of organic osmolytes for osmoregulation by renal medullary cells. AB - The cells in the renal medulla protect themselves from the extracellular hypertonicity in that region of the kidney by accumulating large amounts of sorbitol, inositol, glycerophosphorylcholine, and betaine. The system is uniquely active in this part of the body, but it represents a throwback to primitive mechanisms by which cells in virtually all organisms, including bacteria, yeasts, plants, and lower animals counteract water stress. In this brief review, we summarize how these "compatible organic osmolytes" help the renal medullary cells to survive, the mechanisms by which the organic osmolytes are accumulated, and how the accumulation is controlled to adjust for changing extracellular NaCl and urea concentrations. The compatible organic osmolytes are all intermediates in important biochemical pathways, and although the medical consequences are not yet fully worked out, it is already apparent that inappropriate accumulation of these solutes has major pathophysiological consequences. PMID- 2246027 TI - Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. AB - Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important. PMID- 2246028 TI - Development of genetic hypertension. Is there a "critical phase"? PMID- 2246029 TI - "White coat" versus "sustained" borderline hypertension in Tecumseh, Michigan. AB - During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had "white coat" hypertension (i.e., high clinic but not elevated home readings). The prevalence of "sustained" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246030 TI - Clinical significance of "white coat" hypertension. PMID- 2246031 TI - Psychosomatic factors in borderline hypertensive subjects and offspring of hypertensive parents. AB - Psychosomatic factors, sympathoneural and sympathoadrenal as well as cardiovascular mechanisms, were studied in 24 patients 18-24 years of age with borderline hypertension, 50 age-matched normotensive offspring of hypertensive parents, and 49 controls with no family history of hypertension. They were compared by projective and questionnaire-based psychological tests and their circulatory and neurohormonal reactivity to mental (Stroop color-word conflict test and arithmetic test) and physical stressors (orthostasis and bicycle ergometry test) were measured. Borderline hypertensive subjects externalized aggression less (p less than 0.05) but internalized it more (p less than 0.05) and were more submissive (p less than 0.05) when compared with controls. Offspring of hypertensive parents showed a similar but weaker pattern. Both risk groups reported more positive interactions with their parents (genetic risk subjects versus controls, p less than 0.05; borderline hypertensive patients versus controls, p = 0.08) and had higher state-anxiety levels (p less than 0.05). There were more subjective symptoms of beta-adrenergic receptor-mediated functions (e.g., tachycardia, tremor) in borderline hypertensive subjects and offspring of hypertensive parents, elevated heart rates (analysis of repeated measures, p less than 0.001), and enhanced plasma norepinephrine concentrations (p less than 0.05) when compared with controls. These findings in subjects at risk for the development of hypertension suggest that psychosomatic factors and sympathetic overactivity are involved in the early phase of hypertension. PMID- 2246032 TI - Enhanced vascular tone in the renal vasculature of spontaneously hypertensive rats. AB - The renal microvascular responses of Wistar-Kyoto and spontaneously hypertensive rats to changes in perfusion pressure were compared using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. In the spontaneously hypertensive rats, the internal diameters of arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 307 +/- 26, 52 +/- 2, 24 +/- 0.9, and 22 +/- 1.2 microns, respectively, at 80 mm Hg. They were 18-35% smaller (p less than 0.05) than the corresponding vessels measured in Wistar-Kyoto rats. In low calcium media, the arcuate and interlobular arteries and the proximal and distal afferent arterioles of spontaneously hypertensive rats exhibited a greater dilation than the vessels of Wistar-Kyoto rats. These observations suggest that the diameters of the preglomerular vasculature of the spontaneously hypertensive rats are reduced because of an elevated vascular tone rather than structural changes narrowing the lumen of these vessels. These results suggest that enhanced vascular tone in the preglomerular vasculature of juxtamedullary nephrons may contribute to the elevated renal medullary vascular resistance and resetting of the pressure-natriuretic relation previously observed in spontaneously hypertensive rats. PMID- 2246033 TI - Renal secretion and hepatic clearance of human multiple renin forms. AB - Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity. PMID- 2246034 TI - Role of endothelium in the response to endothelin in hypertension. AB - The relation between endothelin and acetylcholine (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10(-5) M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 x 10(-6) M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension. PMID- 2246035 TI - Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure. AB - Does the average daily blood pressure correlate with hypertensive cerebrovascular disease better than the casual pressure, as has been reported in other target organ involvement? We investigated the associations of two abnormal findings on brain magnetic resonance imaging suggestive of a vascular etiology, low intense foci (lacunae), and periventricular hyperintense lesions on T1- and T2-weighted images, with both office and average daily blood pressure values in a population of 73 healthy normotensive and hypertensive elderly individuals (70 +/- 6 years old). Lacunae were detected in 34 subjects (47%); the number per subject ranged from 0 to 19 and was significantly correlated with advancing age. Furthermore, these changes were supposedly related to the average of noninvasive ambulatory (24-hour and during awake and asleep periods) pressure recordings but not to office pressures. The grade of periventricular hyperintensity was also significantly associated with advancing age and the average of ambulatory systolic pressure recordings, particularly during sleep, but not with office blood pressure. In comparisons of normotensive, "office hypertensive," and hypertensive subgroups, abnormalities on magnetic resonance imaging were appropriate to the level of the 24-hour blood pressure measurements but not to that of clinic pressure. In hypertensive patients, the presence of electrocardiographic evidence of left ventricular hypertrophy was also associated with greater abnormalities on magnetic resonance imaging. We conclude that ambulatory blood pressure monitoring is superior to casual pressure measurements in predicting latent cerebrovascular disease, which is unexpectedly common in apparently healthy elderly subjects. PMID- 2246036 TI - Effect of age on the efficacy of blood pressure treatment strategies. AB - To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort. We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45-54 years of age, only 30 40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure greater than or equal to 160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially; in the older age group (greater than or equal to 75 years), 65-70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246037 TI - Insulin resistance and blood pressure in young black men. AB - Insulin resistance, independent of obesity or non-insulin-dependent diabetes mellitus, has been demonstrated to be associated with high blood pressure. To determine if insulin resistance could be an antecedent to hypertension in a high risk population, we studied normotensive (112 +/- 12/70 +/- 10 mm Hg) and borderline hypertensive (135 +/- 8/85 +/- 5 mm Hg) lean young black men (22-26 years old) with the euglycemic hyperinsulinemic clamp technique. All subjects had clinically normal oral glucose tolerance. Body mass index and percent adipose mass were the same in both groups. Fasting plasma insulin concentration was significantly higher in the borderline hypertensive group (p less than 0.01). Insulin-directed exogenous glucose metabolism at the same degree of steady-state hyperinsulinemia was significantly lower in the borderline hypertensive group (5.98 +/- 2.22 versus 8.22 +/- 1.96 mg/kg/min; p less than 0.01). For the total population, a significant inverse correlation existed between the glucose infusion rate and systolic blood pressure (p less than 0.01). These data indicate that there is a relation between insulin-mediated glucose uptake and blood pressure. Furthermore, in this high-risk population insulin resistance may precede the onset of established essential hypertension. PMID- 2246038 TI - Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat. AB - The spontaneously hypertensive rat is the most widely studied animal model of essential hypertension, yet the genetics of transmission of high blood pressure in this strain have not been clearly defined. It has been proposed that in the spontaneously hypertensive rat, blood pressure follows a simple additive mode of inheritance and that the hypertension is primarily determined by a single major locus. To investigate the genetics of transmission of increased blood pressure in the spontaneously hypertensive rat, we performed a biometric genetic analysis of multiple, direct measurements of arterial pressure in unanesthetized, unrestrained rats derived by crossing spontaneously hypertensive rats with two different inbred normotensive strains, the Charles River Wistar-Kyoto rat and the Lewis rat. In both crosses, approximately 60% of the variation in blood pressure could be assigned to genotypic variation. The data fit an additive-dominance model of inheritance in which alleles decreasing blood pressure were partially dominant. Thus, in offspring derived from crosses between spontaneously hypertensive rats and Wistar-Kyoto rats or spontaneously hypertensive rats and Lewis rats that are raised under ordinary laboratory conditions, increased blood pressure is not determined by simple additive effects of alleles at a single major locus. The current findings are consistent with the possibility that in the spontaneously hypertensive rat, hypertension may arise from mutations in alleles that ordinarily act in a dominant fashion to suppress blood pressure. PMID- 2246039 TI - The surprising kidney-fluid mechanism for pressure control--its infinite gain! AB - In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966. PMID- 2246040 TI - Antenatal supplementation--effect on iron status of infants. PMID- 2246041 TI - Human milk in infant nutrition. PMID- 2246042 TI - Plasma ferritin in the assessment of iron status of Indian infants. AB - In order to assess the iron nutritional status of infants, plasma ferritin levels were measured in the infants and children at different time intervals till two years of age from two different socio economic groups. While ferritin levels at 3 4 months age were significantly higher in upper income group infants, levels were almost similar in the subsequent infancy between the two income groups. A close correlation was seen between ferritin levels of mothers and infants at 1-3 months of age (p less than 0.001). Prenatal iron supplements (oral or parenteral) resulted in higher ferritin levels at 4-6 months age as compared to placebo group. While the infants born to mothers receiving parenteral iron did not show any evidence of iron deficiency (serum ferritin levels less than 12 ng/ml), 23.5 and 25.0% of infants in oral iron and placebo group had evidence of iron deficiency between 6-12 months. Thus it would appear that improving the iron status of mothers during pregnancy will have significant impact on the iron status of breast fed infants till 6 months. PMID- 2246043 TI - Anemia and physical fitness of school children of rural Hyderabad. AB - Physical fitness status of 119 school children was assessed by administering a simple field level 'running test' without any sophisticated equipment. Moderately anemic children had taken significantly longer time (6.25 min) to complete the 'running test' distance of 1.6 Km. Children with normal hemoglobin (Hb) values and those with higher level normal Hb values took shorter times (7.42 and 7.06 min) to complete the test distance. Deficits of weight for age, height for age and weight for height did not exert independent influence on the 'running time'. Anemic children in the sub-groups of each category of nutritional anthropometric indicator, performed poorly. Anemia proved to be a handicap either in the presence or absence of anthropometric deficits. Mild and moderate anemia imposed handicaps on physical endurance and fitness of school children irrespective of other nutritional deficits. PMID- 2246044 TI - Prothrombin time in first week of life with special reference to vitamin K administration. AB - Prothrombin time was estimated in 100 neonates (80 full term and 20 preterm). Among the full term infants 50 were healthy and 30 sick. Prothrombin time was altered in neonates with birth hypoxia and prematurity (p less than 0.001). Vitamin K administration to anoxic babies resulted in improvement in prothrombin time after 48-72 hours (p less than 0.001). Four newborns has bleeding, 2 had anoxia and 2 were only in preterms who did not receive vitamin K after birth. It is concluded that vitamin K should be given to all preterms and those with difficult deliveries; term, healthy newborns do not need it. PMID- 2246045 TI - Fetal echocardiography in normal pregnancies--a basis for prenatal detection of cardiac malformations. AB - Fifty four fetal echocardiography studies were done in 50 fetuses of ultrasonographically normal and healthy mothers between 16 and 36 weeks of pregnancy. In all cases there was no family history of any congenital heart defects. The purpose was to define normal fetal cardiac anatomy and detect any congenital heart defects. Two dimensional echocardiographic examination was done in long axis, apical four chamber, short axis and subcostal views. M-Mode examination of aorta, left atrium and ventricles was carried out. In majority of cases echos were satisfactory; however, the quality was poor in maternal obesity and oligohydramnios. The technique of cardiac examination differs from that in postnatal life. Two abnormalities were detected in this study, namely, ventricular septal defect (VSD) and paroxysmal atrial tachycardia (PAT). The VSD patient continued the pregnancy and at birth the diagnosis was confirmed, The mother with fetal PAT was put on oral digitalis. She delivered a normal baby with a normal heart rate. PMID- 2246046 TI - Brainstem auditory evoked potentials in children--a normative study. AB - Brainstem auditory evoked potentials (BAEPs) were recorded from electrodes placed at CZ-A1 and A2 positions in sixty nine healthy children of 3-13 years age. Eighty four ears in 42 male children and 54 ears in 27 female children were tested for evoked potentials using 70 dB HL click stimuli, at a rate of 10 per second with 0.1 msec duration and 2048 responses were averaged and replicated in each ear. The values of various absolute peak and interpeak latencies (IPLs) did not show any sex differences. Mean values of BAEP irrespective of sex were calculated. The values for absolute peak latencies were 1.62 +/- .19 for I, 2.63 +/- .2 for II, 3.75 +/- .21 for III, 4.87 +/- .25 for IV and 5.63 +/- .28 for V and those for IPLs were I-V 4.0 +/- .22, I-III 2.13 +/- .14 and III-V 1.87 +/- .16 msec. The recognizability was 100% for waves I, III and V and 92% for waves II and IV. The 99% tolerance limit (TL) of IPLs (mean + 3SD) was taken as a criterion for clinical abnormality. The 99% IL for I-V, I-III and III-V were 4.66, 2.55, 2.35 msec, respectively. PMID- 2246047 TI - Pseudotumor (plasma cell granuloma) of the lung. PMID- 2246048 TI - Hereditary sensory neuropathy: type II. PMID- 2246049 TI - Pyridoxine dependent seizures in a newborn. PMID- 2246050 TI - Transient hyperammonemia in a newborn. PMID- 2246051 TI - Daytime urinary frequency syndrome in childhood. PMID- 2246052 TI - Ultrasound in the diagnosis of choledochal cysts. PMID- 2246053 TI - Cosmetic plumbism. PMID- 2246054 TI - Knowledge of students regarding child nutrition. PMID- 2246055 TI - Persistent pulmonary hypertension in the newborn. PMID- 2246056 TI - Tuberculin conversion after neonatal BCG. PMID- 2246057 TI - Captopril in congestive heart failure. PMID- 2246058 TI - Office management of childhood diabetes mellitus. PMID- 2246059 TI - Characterization of airborne mineral dusts associated with farming activities in rural Alberta, Canada. AB - The dry and windy climate of the Western Canadian prairie provinces, combined with large scale agricultural activities, results in aerosolization or organic and mineral dusts. The purpose of this study was to conduct an environmental and minerological analysis of these dusts in order to estimate the risk for pneumoconiosis in exposed farmer populations. Two districts in central/southern Alberta were chosen for study. One of these regions was representative of a predominantly grain growing district with minimal use of irrigation; the other region was largely devoted to forage and irrigated crop production. Air pollution statistics showed a bi-modal distribution of total suspended particulates (TSP) with peaks corresponding with maximal farm activities in the spring and early fall. Analysis of bulk dust samples obtained from tractor cab filters showed that the majority of particles from both districts were within the respirable range (less than 5 microns). Samples from the forage-crop region contained more organic material, a greater water soluble fraction and had particles that were, on average, smaller and rounder than particles from the grain district. These differences were thought to reflect differences in irrigation patterns and use of fertilizers between the two districts. Free silica (quartz) content was also very variable and ranged from 1 to 17% on a mass basis. Respirable fibrous minerals were occasionally identified, however, no asbestos fibres, fibrous tremolite, or fibrous zeolites were identified. The results indicate that there is potential risk for mineral dust pneumoconiosis in heavily exposed farmer populations and that this risk will be influenced by local and regional factors. PMID- 2246060 TI - Measurements of the impedance of the hand and arm. AB - The mechanical impedance of the hand and arm was studied on ten healthy subjects during exposure to sinusoidal vibration within the frequency range of 2 to 1000 Hz. A special handle for the measurements was constructed. The influence of vibration direction, handle grip, grip force, vibration level, hand-arm posture and sex as well as anthropometric data were studied. The results show that the impedance of the hand-arm mainly depends on the frequency and direction of the vibration stimuli. Higher vibration levels, as well as more firm hand-grips, resulted in higher impedance. Furthermore, the outcome shows that experiments conducted with different hand-arm postures had an active influence on the mechanical impedance. Moreover, the subjects' sex and constitution of the hand and arm affected the impedance to a large extent. PMID- 2246061 TI - Failure of industrial noise to change the patterns of vanilmandelic acid and 17 hydroxycorticosteroids in the urine of the female weavers with hearing loss. AB - The field experiments were undertaken on two consecutive working days on seven female weavers with noise-induced hearing loss (NIHL), and a control group of seven sewers with normal hearing. The first day, urine was collected during the shift (06:00-14:00 h) and at home (17:00-05:00 h) for measurements of 17 hydroxycorticosteroids (17-OH) levels. The following day, the procedure was repeated, but for vanilmandelic acid (VMA) analysis. No significant changes in the hormone levels were found, both concerning the different occupational noise exposure and the periods of a working day. PMID- 2246062 TI - Physiological reactions during brush saw operation. AB - An experimental study of the physiological effects of brush saw operation was performed on eight professional agricultural workers. The experiments were carried out in the field under practical working conditions. Aesthesiometric thresholds (two-point discrimination and depth sense perception), manipulative dexterity, pinch grip force and fingertip skin temperature (FST) were measured before and after exposure to different combinations of static load (handle holding), noise and vibration by using new production brush saws for 5 to 15 min. The changes in the peripheral circulatory, sensorineural and muscular functions of the brush saw workers were not found to be significantly different under the various exposure conditions. Static load accounted for the major part of the changes in aesthesiometric thresholds, pinch grip force and FST after brush saw operation. With respect to baseline measurements, no significant difference in manipulative skill was observed after each exposure period. The weighted vibration accelerations from the right and left handles of a brush saw were 3.13 and 1.80 m/s2, respectively. The assessment of brush saw vibration exposure according to ISO 5349 and the results of FST measurements were consistent with the findings of some epidemiological surveys indicating a low risk of vibration induced white finger among brush sawyers. This investigation pointed out that the increase in the aesthesiometric thresholds was mainly determined by handle holding, and that the reduction in gripping force during actual work was related to the duration of brush saw operation. Therefore, prolonged static overload on the nerves, muscles and joints of the hand-arm system could explain the increased risk of musculoskeletal and sensorineural disorders found among brush saw users. PMID- 2246063 TI - Vibration perception threshold of forest worker's finger during temporary obstructed blood circulation. AB - Vibration detection threshold (VPT) of 149 professional forest workers was measured during a compulsory annual health examination. The authors' earlier developed measuring method for VPT of finger was modified. The blood circulation of the hand was obstructed for 6 min and VPT was measured 4 min after releasing the obstruction. VPTs of all forest workers increased during obstruction. In forest workers suffering from decreased hand grip force (decreased HGF) the increase of VPT differed significantly from forest workers without symptoms, and VPT in the former group still increased after releasing the obstruction. VPT remained also at the raised level after releasing the obstruction with forest workers suffering from vibration-induced white finger (VWF). Nevertheless, on an individual basis even the modified measuring method failed to discriminate subjects without symptoms from those with symptoms of hand-arm vibration syndrome. The raised VPT and sensitivity for obstruction of blood circulation suggest that the reason for decreased HGF in forest workers may be a consequence of an injury in the peripheral nerves. PMID- 2246064 TI - Skin sympathetic activity in the tibial nerve triggered by vibration applied to the hand. AB - The effect of vibration applied to the hand on skin sympathetic activity (SSA) in the lower limbs was studied in five healthy subjects. SSA from the right tibial nerve at the popliteal fossa, plethysmogram from the right index toe and perspiration from the sole of the right foot were measured when vibration of 100 m/s2 at 60 Hz was applied to the left palm for 1 min. The SSA response to vibration exposure differed among subjects, but every subject showed an increase in SSA from the tibial nerve when vibration was applied to the hand. Decrease in amplitude of plethysmogram from the toe was also found in all subjects. One subject displayed a remarkable increase in perspiration on the sole of the foot together with a great increase in SSA. The present findings indicated that even vibration exposure of the hand triggers sympathetic activity in the tibial nerve innervating the foot, and causes vasoconstriction of the toe and perspiration on the sole of the foot. PMID- 2246065 TI - Importance of exposure to gaseous and particulate phase components of tobacco smoke in active and passive smokers. AB - The uptake of tobacco smoke constituents from gaseous and particulate phases of mainstream smoke (MS), inhaled by smokers, and of environmental tobacco smoke (ETS), breathed in by non-smokers, was investigated in two experimental studies. Tobacco smoke uptake was quantified by measuring carboxyhemoglobin (COHb), nicotine and cotinine in plasma and urine and the data obtained were correlated with urinary excretion of thioethers and of mutagenic activity. An increase in all biochemical parameters was observed in smokers inhaling the complete MS of 24 cigarettes during 8 h, whereas only an increase in COHb and, to a minor degree, in urinary thioethers was found after smoking the gas phase of MS under similar conditions. Exposure of non-smokers to the gaseous phase of ETS or to whole ETS at similar high concentrations for 8 h led to identical increases in COHb, plasma nicotine and cotinine as well as urinary excretion of nicotine and thioethers which were much lower than in smokers. Urinary mutagenicity was not found to be elevated under either ETS exposure condition. As shown by our results, the biomarkers most frequently used for uptake of tobacco smoke (nicotine and cotinine) indicate on the one hand the exposure to particulate phase constituents in smoking but on the other hand the exposure to gaseous phase constituents in passive smoking. Particle exposure during passive smoking seems to be low and a biomarker which indicates ETS particle exposure is as yet not available. These findings emphasize that risk extrapolations from active smoking to passive smoking which are based on cigarette equivalents or the use of one biomarker (e.g. cotinine) might be misleading. PMID- 2246066 TI - Aromatic DNA adducts in white blood cells of coke workers. AB - White blood cell DNA adducts were measured in coke workers, local controls and countryside controls using the 32P-postlabelling technique. The method detected aromatic adducts including those formed by polycyclic aromatic hydrocarbons (PAHs). Coke workers are heavily exposed to PAHs particularly when working at the batteries. A difference in adduct levels was noted between the coke workers at the battery as compared to other jobs. The adduct levels in the non-battery were higher than those in the countryside controls. PMID- 2246067 TI - Adjustment for urinary flow rate: an improved approach to biological monitoring. AB - The use of urinary monitoring in medical surveillance programs in industry requires the development of an accurate and unbiased index of urinary concentrations of occupational toxins. To examine the effects of urinary flow rate on adjusted and non-adjusted urinary excretion of 11 heavy metals and organic substances, 19 metal-foundry workers were studied during four time periods of the day under conditions of water restriction and loading. The results indicate that urinary flow rate significantly affects not only the non-adjusted urinary concentration for all substances, but also affects timed excretion as well as concentrations adjusted to urinary specific gravity and to urinary creatinine during any time period of the day. On the other hand, the concentration adjusted to urinary flow rate (UF-adjusted concentration) is independent by definition of urinary flow; therefore, this adjustment is applicable for highly diluted and highly concentrated urine samples without repetition of urine collection. It is concluded that UF-adjusted concentration is a useful index for the measurement of most urinary substances, while adjustments to urinary specific gravity and to urinary creatinine concentration have only limited utility in evaluating toxin levels in spot urine samples. PMID- 2246068 TI - Accumulation of carbon disulphide metabolites. AB - Biological monitoring for carbon disulphide (CS2) exposure performed using the iodine-azide test (IAT) and 2-thiothiazolidine-4-carboxylic acid (TTCA) test in urinalysis of workers with high exposure to CS2 (112-142 mg/m3, n = 34), workers with low exposure (4-7 mg/m3, n = 16), and non-exposed university workers (n = 10). Pre-shift and post-shift urine specimens were collected on three consecutive days in the exposed and for only one day in the non-exposed. According to the findings the specificity and the sensitivity seem to be low for the IAT and high for the TTCA test. Contrary to a previous report all pre-shift urine samples showed negative IATs. The TTCA test was positive in pre-shift urine even after 32 to 63.5 h without exposure, and values tended to increase during consecutive days of exposure in highly exposed workers. The possible health implications of these findings should be further investigated. PMID- 2246069 TI - Comparison of conidial and mycelial allergens of Alternaria alternata. AB - Alternaria allergens, separated by SDS polyacrylamide gel electrophoresis and transferred onto a nitrocellulose membrane, were identified using sera from Alternaria-allergic patients. 30 Alternaria components of spore and mycelium, ranging in molecular weight from more than 150 to 12 kD, bound IgE antibodies. 15 were detected by more than 25% of the sera and only 4 (85, 56, 42, 31 kD) by more than 50% of the sera. Among these four major allergens, the 56-kD component was present mostly in the spore extract, the 85- and 42-kD fractions in the mycelium extract and the 31-kD in both extracts. The 31-kD component showed the highest IgE binding and the highest frequency of binding (95% with mycelium extract and 79% with spore extract). It was composed of two subunits. PMID- 2246070 TI - Interleukin-4 gene expression in high and low IgE responder mice. AB - Interleukin-4 (IL-4) gene expression in murine spleen cells was examined by stimulation with concanavalin A (Con A). Spleen cells from a DBA/2 strain of mice, a high IgE responder, expressed IL-4 mRNA within 3 h after incubation with Con A. Maximal IL-4 mRNA expression was observed 6-9 h after stimulation. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from high IgE responder strains of mice. A trace amount of mRNA was induced in spleen cells from low IgE responder (SJL) mice. The amount of mRNA induced in spleen cells from an intermediate IgE responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA after stimulation with Con A. Time course and optimal concentration of Con A for the expression of IL-4 mRNA were essentially the same in high (DBA/2) and low (SJL) responder strains of mice. The decreased expression of IL-4 mRNA in low IgE responder spleen cells upon stimulation was not due to the decrease in Thy-1 positive cells or L3T4-positive cells in the spleen. The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression. PMID- 2246071 TI - Remarkable increases of salivary IgE levels in allergic syndromes. AB - Serum and salivary IgE levels were tested by indirect ELISA in patients with allergic contact dermatitis and allergic asthma or rhinitis. The remarkable increases of salivary IgE (from 928.4% mean augmentation in allergic asthma or rhinitis to 2686.2% in allergic contact dermatitis) suggest the idea of using saliva in IgE titration. PMID- 2246072 TI - Preparation of allergen extracts from the green alga Chlorella. Studies of growth variation, batch variation, and partial purification. AB - Allergen extracts were prepared from different raw materials of three strains of the unicellular green alga Chlorella (C. vulgaris, C. homosphaera and C. saccharophila). Growth variation, batch variation and composition of partially purified extracts were studied by analyzing total protein and carbohydrate content, protein and IgE-binding patterns and allergenic potency. Chlorella allergens were produced in the same proportions in early and late exponential growth phases but appeared partly degraded in the stationary phase. Uniform growth and extraction from Chlorella cells in the late exponential phase were demonstrated. Partially purified extracts from cells in late exponential phase contained 50% protein of the dry weight compared to 20% in crude extracts. The carbohydrate content was 20-30% of the dry weight of both crude and purified extracts. The allergenic potency of the purified extracts was 150-340% of the crude extracts, as assayed by RAST inhibition. The purified C. vulgaris extract showed a reduced IgE binding compared to crude extracts, while C. homosphaera and C. saccharophila extracts exhibited consistent IgE binding and are therefore suitable for in vivo and in vitro studies of allergenic properties of Chlorella. PMID- 2246073 TI - Antigenic analysis of group I house dust mite allergens using random fragments of Der p I expressed by recombinant DNA libraries. AB - Antigenic regions of a major house dust mite allergen, Der p I, were identified by a recombinant DNA strategy employing the technique of random fragmentation. Fragments of cDNA coding for Der p I were produced by sonication and used to construct lambda gt 11 expression libraries. Analyses of recombinant fragments reactive with a rabbit anti-Der p I antiserum showed that the B cell determinants expressed in Escherichia coli were limited, with the majority (86%) of antigenic clones isolated mapping to the region comprising amino acid sequence position 60 80. To define antigenic regions of Der p I more precisely, selected overlapping fragments were subcloned into the expression vector pGEX-1. Dot blot immunoassay and immunoabsorption studies using individual fusion proteins revealed five regions - 34-47, 60-72, 82-99, 112-140, and 166-194 - to contain B cell determinants responsible for the antigenicity of recombinant Der p I. Absorption of the antiserum with Dermatophagoides pteronyssinus extract removed reactivity to all fragments, whereas absorption with an extract from the related mite Dermatophagoides farinae removed reactivity to peptides containing residues 34 47, 60-72, and 166-194, but not 82-99 and 112-140. Similarly, rabbit anti D.farinae reacted strongly with peptides containing residues 34-47, 60-72, and 166-194, but not residues 82-99 and 112-140 which again showed antigenic differences in these residues between the group I allergens. PMID- 2246074 TI - Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenes. AB - Seven different synthetic thiosulfinates, and cepaene- and/or thiosulfinate-rich onion extracts were found to inhibit in vitro the chemotaxis of human granulocytes induced by formyl-methionine-leucine-phenylalanine in a dose dependent manner and at a concentration range of 0.1-100 microM. Diphenylthiosulfinate showed the highest activity and was found to be more active than prednisolone. The anti-inflammatory properties of onion extracts are related, at least in part, to the inhibition of inflammatory cell influx by thiosulfinates and cepaenes. PMID- 2246075 TI - Isolation and characterization of rat carcinoembryonic antigen. AB - A rat tumor-associated antigen with properties similar to those of human carcinoembryonic antigen (CEA) has been detected with rabbit immune sera in extracts of transplantable rat colonic adenocarcinoma, RCA-1. This antigen, termed rat CEA, was also detectable by a monkey antihuman CEA serum and a rat monoclonal antibody to rat CEA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of perchloric acid extracts of RCA-1 tumor, followed by immunoblotting with the above-mentioned anti-CEA reagents, revealed that rat CEA activity resided in components with a molecular weight of approximately 350 kD. The glycoprotein nature of these components was indicated by positive staining with periodic acid-Schiff. Sephadex G-200 chromatography, as well as Sepharose 4B chromatography with and without sodium dodecyl sulfate indicated that the 350-kD components existed in the extracts as molecular aggregates. The 350-kD material, which had been purified by an affinity column containing rat monoclonal antibodies to rat CEA, reacted with the rabbit and monkey anti-CEA sera. This provided strong evidence that serological activity of rat CEA was confined to the 350-kD components. PMID- 2246076 TI - Immunohistological analysis of nerve granulomas in neuritic leprosy. AB - Immunohistological analysis of infiltrates of nerves in patients with neuritic leprosy was carried out using monoclonal antibodies defining T cell subsets, Langerhans cells, HLA DR antigens, and indirect immunofluorescence. In all, eight nerves were analyzed. 2 of the 8 nerves showed epithelioid cell granulomas surrounded by large numbers of lymphocytes. The predominant lymphocytes in these granulomas were activated T cells expressing CD3 and HLA DR antigens. The proportion of CD3+ and CD4+ cells was higher than that of CD8+ cells. The ratio of CD4+/CD8+ cells in these two biopsy specimens was 5.6 and 1.5, respectively. In these nerves CD4+ cells were diffusely scattered into epithelioid cell granulomas, while CD8+ cells were localized at the periphery of the granuloma. The remaining six nerves showed macrophages containing numerous bacilli, and a few lymphocytes and plasma cells diffusely distributed into the granuloma. In these nerves, only occasional lymphocytes expressing CD3 or CD4 or CD8 and HLA DR antigens were noticed. In two fo the biopsy specimens, a small proportion of CD8+ cells were visualized. Macrophages and Schwann cells were HLA DR+ in all nerves. CD1+ cells were not seen in the infiltrates of any of these nerves. A similar pattern and distribution of cells was noticed in the nerve granulomas of tuberculoid and lepromatous leprosy. These findings suggest that the mechanisms of nerve damage in the patients with neuritic leprosy could be either immunological or non-immunological, depending on the nature and characteristics of the infiltrates. PMID- 2246077 TI - Mouse IgE response against exoantigens of Trypanosoma cruzi. AB - This work describes the occurrence of anaphylactic antibodies against exoantigens of Trypanosoma cruzi in infected or immunized mice. The results obtained show that the exoantigens induce an IgE response when injected into mice with complete Freund's adjuvant or in animals infected with 10(2) trypomastigotes. Among the antigens recognized by anti-exoantigen IgE, two molecules of 27 and 45 kD were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by western blotting. Immunofluorescence analysis located some target antigens on the parasite surface. PMID- 2246078 TI - Antiallergic and anti-inflammatory action of tioxamast in rats. II. Anti inflammatory action in vivo. AB - Tioxamast is an antiallergic drug that inhibits anaphylaxis in various models in rats, and it inhibits the release and synthesis of certain mediators of inflammation [see Tarayre et al., this issue]. Here we report that the drug also has an anti-inflammatory effect in vivo in various nonimmunological models in rats. It reduces zymosan-induced inflammation in the paw and pleural cavity, starting at doses from 1.5625 to 3.125 mg/kg given intraperitoneally. In pleurisy, tioxamast lowers the concentration of leukotriene B4 (LTB4) in the exudate, at doses from 50 mg/kg i.p. Also, at doses from 12.5 mg/kg i.p., the compound reduced PAF-acether-induced pleurisy and the concentrations of LTB4 and peptidoleukotrienes in the exudate. An anti-inflammatory action against carrageenin-induced edema of the paw was seen only at doses of 50 mg/kg i.p. or more. The anti-inflammatory and antiallergic effect of tioxamast makes it a potentially useful drug in the treatment of allergies in humans. PMID- 2246079 TI - Relationship between LTC4 generation of hypodense eosinophils and bronchial hyperreactivity in asthmatic children. AB - In 19 asthmatic children aged 6-16 years, the degree of bronchial hyperreactivity was determined in relationship to the concentration of inhaled histamine which caused a fall of the specific conductance (sGaw) to 60% of the baseline value PC60sGaw. At the time of lung function testing, a sample of heparinized blood was obtained from each patient. Eosinophils were purified and separated into a normodense and hypodense fraction by Percoll gradient centrifugation. After in vitro stimulation by ionophore A 23187, the leukotriene C4 (LTC4) content was determined in the culture supernatants. Hypodense eosinophils of the 13 children with a histamine threshold lower than 1 mg/ml generated significantly (p less than 0.01) larger amounts of LTC4 (0.8-36.3 ng/10(6) cells) when compared to 6 children with a histamine threshold higher than 1 mg/ml (0.7-12.1 ng/10(6) cells) and 12 healthy controls (0.4-8.2 ng/10(6) cells). Preincubation of eosinophils with platelet activating factor (PAF) induced an enhanced LTC4 production, not only in hypodense cells from both asthmatic groups but also in normodense cells from patients with severe hyperresponsiveness. These results are consistent with other results which suggest an important role of eosinophils, their activation by PAF and enhanced release of spasmogenic LTC4 in the pathogenesis of asthma. PMID- 2246080 TI - Modulation of the immune response to allergens: phospholipase A degradation products suppress IgG and IgE response in mice. AB - Degradation products of phospholipase A2 (PLA2), the major allergen of honeybee venom, were prepared by peptic digestion of the enzyme and fractionated by molecular exclusion chromatography. The largest of the isolated products, P-1, was found to be a centrally nicked PLA2 molecule with a loss of several amino acids. It was examined for its antigenic, immunogenic and immunosuppressive properties. This peptic product was unable to block antigen-antibody reactions between PLA2 and anti-PLA2 antibodies and was incapable of inducing passive cutaneous anaphylaxis in rat skin sensitized with mouse anti-PLA2 IgE antibodies. BDF1 female mice injected intravenously with P-1 exhibited suppressed IgG and IgE anti-PLA2 responses to a subsequent PLA2 immunization. Intravenous administration of P-1 to mice with ongoing immune response to PLA2 resulted in decline of antigen-specific IgE titers. Transfer of splenic T cells from mice injected with P-1 into naive recipients caused profound suppression of the response to subsequent immunization with PLA2 indicating presence of PLA2-specific T suppressor cells. These results indicate that a degradation product of PLA2 prepared by peptic digestion lost antigenic and immunogenic properties of the intact enzyme but retained immunosuppressive properties, thus offering a novel approach to allergen immunotherapy. PMID- 2246081 TI - Serum antibodies reactive with Saccharomyces cerevisiae in inflammatory bowel disease: is IgA antibody a marker for Crohn's disease? AB - Sera from patients with Crohn's disease (CD) and ulcerative colitis (UC) have been evaluated for antibodies reactive with Saccharomyces cerevisiae (anti-Sacc antibodies) using an enzyme-linked immunoassay (ELISA). IgG anti-Sacc antibodies were detected in 63% (25/40) of CD patients, compared with 15% (4/27) of UC patients (p less than 0.001) and 8% (5/60) healthy adult controls (p less than 0.001). Furthermore, the prevalence of detectable IgG anti-Sacc antibodies in adult patients with coeliac disease, dermatitis herpetiformis, irritable bowel syndrome or atopic eczema was not significantly different to controls. In comparison, the prevalence of detectable IgG anti-Escherichia coli antibodies was not significantly different between CD (75%) or UC (79%) patients. More particularly, elevated levels of serum IgA anti-Sacc antibodies were detected in 17/40 CD patients, but in none of the 27 UC patients. These data confirm that serum antibodies reactive with S. cerevisiae are strongly associated with CD and further show that serum IgA anti-Sacc antibodies may be specific for this disorder. PMID- 2246082 TI - Contact hypersensitivity induces plasma interleukin 6. AB - Previous studies in this laboratory have revealed that elicitation reactions in contact-sensitized mice correlate closely with elevations in the serum concentration of acute-phase proteins. Regulation of the hepatic synthesis of acute-phase proteins is one of the many biological functions ascribed to interleukin 6 (IL-6). We now provide evidence that contact reactions are also associated with a rapid and substantial increase in the plasma concentration of IL-6. Quantitative assessment of plasma IL-6 may provide a useful serological method for the evaluation of experimental allergic contact dermatitis in mice, and possibly in other species. PMID- 2246083 TI - Genetic influences on tobacco use: a review of human and animal studies. AB - This paper provides an overview of the literature which indicates that genetic factors regulate the use of alcohol and tobacco by humans. The methods used to make genetic assessments in humans and the results obtained are discussed. Studies using animals have been helpful in identifying simpler behavioral components of the dependence process that are regulated by genetic factors. An overview of the genetic methods used most often in animal studies is presented along with an in-depth discussion of how these methods have been useful in uncovering genetic influences on nicotine responses in animals. Data which indicate that genetic factors regulate brain nicotinic receptor numbers and response to nicotine are also included as examples of how genetic strategies have been useful in increasing our understanding of how genes may influence behavior. PMID- 2246084 TI - Genetics of responses to drugs of abuse. AB - Genetic differences in drug metabolism, in the number of drug receptors in the brain, and in drug-seeking behavior may contribute to the variability of individual responses to drugs of abuse. Genetic models include inbred strains, mutants, sublines, and selectively bred mice and rats. They have been used to examine acute and chronic effects of narcotics, stimulants, and alcohol as well as drug-seeking behavior, withdrawal syndromes, and the stress-induced release of endogenous opioids. These genetic models should prove helpful in defining individual differences in susceptibility to addiction. PMID- 2246085 TI - Genetic studies of alcoholism. AB - This paper reviews recent developments in the evaluation of genetic factors in alcoholism. After presenting the results of family, twin, and adoption studies, the authors turn to investigations focusing on children of alcoholics. An emphasis is placed on the finding of a decreased intensity of reaction to alcohol in sons and daughters of alcoholics. The potential implications of these findings are discussed. PMID- 2246086 TI - Knowledge about and behaviors affecting the spread of AIDS: a street survey of intravenous drug users and their associates in New York City. AB - An informal survey of knowledge about and behaviors relevant to the spread of AIDS was conducted on the street in New York City during October 1986. The sample (n = 204) includes IV drug users (60%) and others (40%). The informal nature of the interview suggests that respondents gave "salient" answers rather than the complete answers that would be expected in a formal interview situation. A smaller proportion of respondents reported salient knowledge about drug-related transmission of AIDS than had been found in other populations, using formal interview methods. A close association was found between any accurate knowledge about spread of AIDS and likelihood of practicing one or more risk reduction behaviors. New users (persons who had been using drugs for only 1 or 2 years) were significantly less likely than others to have salient knowledge about AIDS transmission and also less likely to practice risk reduction measures. PMID- 2246087 TI - Smoking behavior and personality characteristics in Polish adolescents. AB - We report here clear-cut evidence that personality characteristics, at least those measured by the Maudsley Personality Inventory and a semantic differential rating of smokers and nonsmokers, are related to smoking behaviors in 1,000 Polish adolescents. The pattern of relationships replicates well that reported by others based on data collection from other cultures. The use of such findings in intervention and prevention attempts with cigarette smoking or other self-abusive behaviors remains to be evaluated in the future. PMID- 2246088 TI - Drug use and disciplinary actions among 300 nurses. AB - A survey of 300 U.S. nurses recovering from alcohol and other drug dependency was conducted to describe the effect of drug use on job performance and related disciplinary actions. Subjects reported experimentation with or dependence on a variety of drug categories. Many visible effects on job performance were reported but only 23% reported disciplinary action against their nursing licenses. Females and older nurses were more often dependent on alcohol, while younger nurses and males reported narcotic dependency with greater frequency. Narcotic use was significantly related to disciplinary action. PMID- 2246089 TI - Conditional factors of maturing out: legal supervision and treatment. AB - This study is third in a series exploring the conditional nature of the process of maturing out of narcotics addiction over time. Hypotheses are tested about the relationship of two selected social interventions, legal supervision and methadone maintenance treatment, on maturing out. The technique of log linear modeling is used on long-term follow-up data from 375 admissions to the California Civil Addict Program. Results suggest that maturing out may be conditional on methadone treatment participation, which reduces addicted use to a greater extent for older addicts, but does not seem to be related to legal supervision, which is equally effective regardless of age. PMID- 2246090 TI - Psychological and behavioral impact among intravenous drug users of learning HIV test results. AB - In 1984 as part of a New York City study to examine the prevalence of HIV infection in a substance-abusing population and to test the validity of HIV screening kits, 94 patients at the New York VAMC were tested. Results were made available to 50 (35 seronegative, 15 seropositive) patients in January 1986. Psychological and behavioral impact of learning test results was assessed using standardized psychiatric rating scales. A comparison group of 31 nontested subjects were also evaluated. Ratings were done preresults, approximately 1-2 weeks after results, and 8-10 weeks after informing patients of their HIV status. No major stress reactions were observed. Seropositives experienced a higher level of anxiety 1-2 weeks after learning results but anxiety generally diminished; they made significant behavior changes which were maintained. Seronegatives experienced relief and maintained IV drug risk reduction behavior. Anxiety about contracting AIDS increased in nontested subjects as the study progressed. PMID- 2246091 TI - Physicians' attitudes toward substance abuse and drug testing. AB - Responding to a survey, 303 physicians provided opinions about permissibility of substance use among eight occupational groups, appropriateness of drug-screening programs by employers, and the role of physicians in managing substance abuse problems. The majority felt that neither drugs nor alcohol should be used at lunch by any individuals, but that alcohol and to some degree marijuana use was permissible after work or on weekends. Physicians could not agree about reliability or use of drug-testing programs. However, most believed that employee drug screening was more appropriate after evidence of poor job performance rather than screening all employees or applicants. PMID- 2246092 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2246093 TI - Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma. AB - The prognostic value of clinicopathologic data and tumor cell morphometry was assessed in 49 consecutive patients with advanced epithelial ovarian carcinoma (Stage III-IV as defined by the International Federation of Gynaecologists and Obstetricians [FIGO]). Single-variant analysis proved that nuclear area at the 10th, 50th, and 90th percentiles and nuclear density were the strongest prognostic factors. To assess difference in prognostic influence between morphometric and clinicopathologic factors, Cox regression analysis was carried out and revealed nuclear density and age as prognostically significant (p less than 0.0003 and p less than 0.0004, respectively). Choice of chemotherapy, FIGO stage, histologic grade, and mitotic activity index (MAI) were not of additional prognostic importance. Objective measurement of morphometric factors is simple, highly reproducible, and adequate for routine work and promises to be of clinical value in therapeutic decision-making in advanced ovarian carcinoma. PMID- 2246095 TI - Epithelial hyperplasia of the fallopian tube. PMID- 2246094 TI - Mullerian adenofibroma of the uterus with invasion of myometrium and pelvic veins. AB - Two cases of mullerian adenofibroma of the uterus with unusual features are described. The tumors were encountered in patients 51 and 70 years of age who presented with abdominal pain and postmenopausal bleeding, respectively; both patients were found to have a pelvic mass. Intraoperative findings included an enlarged uterus in each case, and in one of them, uterine rupture and worm-like plugs of tumor within veins of both broad ligaments. Examination of the hysterectomy specimens revealed polypoid endometrial tumors that deeply invaded the myometrium. On histologic examination, both tumors were composed of an intimate admixture of benign endometrial-type glands and a moderately cellular stroma containing fibroblasts with benign nuclear features and very low mitotic activity (less than one mitotic figure per 10 high-power fields). Both tumors infiltrated the myometrium almost to the serosa, and one of them grew within the lumens of large myometrial veins. The patients had uneventful postoperative follow-up periods of greater than 3 years. This report indicates that rare, otherwise typical uterine adenofibromas can exhibit invasive properties and may have a malignant potential. PMID- 2246096 TI - Between life and death: aging. PMID- 2246097 TI - Is death just another psychosomatic disease? PMID- 2246098 TI - Influence of a Maharishi Ayur-vedic herbal preparation on age-related visual discrimination. AB - An ancient system of natural medicine--Maharishi Ayur-Vedic--prescribes certain herbal formulas to enhance cognitive functioning, prevent illness, and alleviate the detrimental effects of the aging process. A double-blind study was conducted to test the effect of an Ayurvedic herbal preparation, Maharishi Amrit Kalash (MAK), on an age-related alertness task. Forty-eight men over 35 years of age were randomly assigned to receive MAK tablets or a closely matched placebo twice daily for six weeks. A visual discrimination task consisted of the identification of the exact location of a stimulus "v" within an array of x symbols in tachistoscopic presentations. The MAK group improved significantly more in their performance of this task after three and six weeks of treatment relative to the placebo group. Performance was highly correlated with age, and because successful performance apparently requires an unrestricted flow of homogeneous attention as well as focalized concentration, it is concluded that MAK may enhance attentional capacity or alertness, and thus reverse some of the detrimental cognitive effects of aging. PMID- 2246099 TI - Psychological aspects of long-distance running among Chinese male runners in Hong Kong. AB - Forty-four Chinese male long-distance runners were surveyed regarding their running history, running habits, and injuries, as well as their experience of the "runner's high" phenomenon. The typical runner could be described as single, in his late 20s, well-educated, and running 60 km a week. He was also likely to be controlled and disciplined, not risk-taking, and not oriented intellectually or esthetically. While he was motivated to run to improve his physical health, he derived benefits for his emotional well-being from his running. Implications for the use of running as a therapeutic adjunct are discussed. PMID- 2246100 TI - Self-injury in psychiatric in-patients. AB - Suicide and self-injury in-patients were identified on the basis of a retrospective content analysis of special incidence reports completed the preceding year at an urban state psychiatric hospital. Select clinical and biodemographic variables were then examined, and in order to determine the importance of these variables in the prediction of incident severity, a multiple regression analysis was performed. Schizophrenic patients were found to be significantly over-represented among both the self-injury and suicide patients. PMID- 2246101 TI - Repression and somatization: a case history of hemodynamic activation. AB - A 52-year-old woman presented to the office about 2 and 1/2 years after the death of her husband from cancer. She had multiple hemodynamic and cardiovascular disorders such as hypertension, angina, tachycardia, dysmenorrhea, cardiac ectopics, and very cold hands and feet. The patient complained of tension and insomnia but refused to take any medications because of allergic responses to them. Hence, a relaxation and psychotherapeutic approach was adopted. Psychometric testing revealed extreme defensiveness (including repression). The patient had never mourned for her husband. Therapy helped her overcome her bereavement, tension, and insomnia. In addition, many of her physical manifestations subsided considerably during therapy. PMID- 2246102 TI - A sense of control, health, and illness: exploring the mind-body relationship and the socio-cultural/spiritual context: reflections on Bali. AB - Research has shown that there is a much more intimate and complex relationship between the "mind" and "body" than heretofore acknowledged within the predominant Western scientific paradigm; and that a "sense of control" may be one of the more important variables mediating that relationship. Furthermore, even when this "mind-body" relationship is studied, it is often done so in a reductionist way- at a psychophysiological level within the individual, thereby ignoring the socio cultural context within which it is embedded. To address these issues, this article examines the mind-body relationship within the socio-cultural/spiritual context of Bali. Specifically examined are: (1) the culture's underlying assumptions about the mind-body-spirit connection across developmental and life cycle issues (including physical illness, and death); (2) the importance of maintaining a sense of control, harmony, and balance, within oneself, one's community, and the cosmos; and (3) the implications of those views for a control based model of positive health. The article concludes with: (1) a discussion of why control seems to be such an important "construct" in human evolution; (2) an examination of the costs and benefits of different methods of maintaining a sense of control and orientation; and (3) and a call for efforts toward a unifying theory of human control. PMID- 2246103 TI - A unified theory of aging. AB - In the 1988 issue of this Journal, in the article: "Aging: Causes and control," 17 aging theories were presented. Those theories are now amplified, and an additional 7 theories are considered. Utilizing concepts from these theories, a unified theory of aging is then presented. PMID- 2246104 TI - Treatment needs of alcohol-dependent women. AB - Research has suggested specific features of alcohol-dependent women in comparison with men. The women usually display: (1) solitary drinking; (2) neurotic and family problems; (3) risk of early health impairment; and (4) abuse of other drugs. These factors should be taken into account in therapy. The in-patient program described is based on the principles of a therapeutic community and systems theory. It includes group and family therapy, education, relaxation training, yoga, a therapeutic club for former in-patients, and use of drugs such as disulfiran. Alcohol-dependence in women has become a growing problem. Adequate therapy is needed, but prevention is even more important. PMID- 2246105 TI - Treatment of bulimia with hypnosis involving awareness and control in clients with high dissociative capacity. AB - The details of an easily replicable intervention using hypnosis in the treatment of bulimia are presented. Follow-up data at one month, three months, six months, and one year indicated that the intervention appeared to be effective in two out of the three cases presented. Factors affecting treatment outcomes are discussed. PMID- 2246106 TI - Exogenous corticosteroid effects on mood and cognition: case presentations. AB - Eight patients who had undergone greater than five years of intermittent treatments with corticosteroids volunteered to be interviewed about their experiences. Seven patients stated they were not warned by their physicians of the possible psychiatric side effects. Five patients did not inform their physicians when symptoms did occur. The patients complained of insomnia, depression, hypomania or euphoria, confusion, and memory problems. Based on these reports, the frequency of affective and cognitive side effects of exogenous corticosteroids may be much higher than has been previously reported. The studies in the literature are discussed and recommendations are given for evaluating these side effects in patients who are treated with corticosteroids. PMID- 2246107 TI - Incidence of stress-related disorders among American and Brazilian men and women. AB - Cross-cultural differences in physical and emotional responses to stressors are reported in this study. Among professionals (e.g., managers, supervisors), the incidence of stress-related disorders can have remarkable impact upon organizational performance as well as personal well-being. In order to study the relationship of nationality and gender to stress-related disorders, 148 American and 180 Brazilian professionals completed a questionnaire asking them to identify their unique responses to occupational stressors. Statistical analysis indicated that significant differences exist between the responses based upon both nationality and gender. Specifically, Americans reported a significantly higher incidence of allergies and irritable bowel syndrome, while Brazilians reported a higher incidence of Raynaud's syndrome (major manifestations are cold hands/feet). The males reported a higher incidence of high blood pressure and TMJ dysfunction/bruxism (a major manifestation is teeth grinding), while the females reported a higher incidence of tension headaches. The results are discussed in comparison to other cross-cultural and cross-gender studies with similar outcomes. PMID- 2246108 TI - The reliability of EMG muscle scanning. AB - The reliability of a surface EMG scanning procedure was investigated for the right and left aspects of ten muscle sites using a large clinical sample of 102 chronic patients. Two neutral postures (sitting/standing) were systematically studied on three occasions approximately one hour apart on the same day. The multivariate analysis of RMS microvolts indicated no significant effects for Age, Gender, Muscle Site, Aspect, or Period. The range of the Pearson correlations was 0.41 to 0.94 when all muscle sites, aspects, postures, and periods were considered. The median correlation was found to be 0.64. The pattern of reliability was seen to be slightly higher in the lower back while standing. The results indicate that with adequate attention to skin preparation, EMG sensors held in place by hand with a light pressure produced reliable results. PMID- 2246109 TI - The restoration of control in facial muscles affected by Bell's palsy. AB - Electromyographic biofeedback and behavioral control techniques were used to treat two patients who suffered from Bell's palsy. Both patients (one case with a long history of Bell's Palsy which included extensive surgery to her face, the other of more recent onset) appeared to have benefited from these procedures and also perceived themselves as having done so. It is recommended that the noninvasive techniques outlined should be tried at an early stage in this condition in order to: (1) prevent the acquisition of inappropriate behavior; (2) accelerate progress toward normal facial functioning; and (3) reduce the need for any surgical intervention. PMID- 2246110 TI - Axiological aspects of comparing psychotherapy and meditation. AB - This article is a general reflection on meditation and psychotherapy considered from the metatheoretical standpoint of the philosophy of science and axiology. It is concluded that in practice they differ in respect of functions, goals, and relation between participants. While the traditional aim of psychotherapy is to restore health, that of meditation is self-development through a specific way of life and practices. The master passes on his discipline a definite system of values and philosophy of life, whereas the therapist assists the patient in eliminating pathological symptoms through psychotherapeutic maneuver. The pitfalls of unwarranted interpretation of scientific data on meditation are presented. PMID- 2246111 TI - Music ability and altered states of consciousness: an experimental study. AB - Some theoretical researchers have hypothesized links between music and altered states of consciousness. Music can influence the induction and maintenance of hypnosis. In addition, some altered states of consciousness may stimulate the musical creativity and musical production of mankind. In this research, the relationship between music and altered states of consciousness is studied from an experimental point of view. The experiments were conducted with 30 university students divided into two groups: the Hypnosis Group and the Control Group. The "Test di abilita musicale" was applied. The first group did the retest after post hypnotic suggestions and the second in waking conditions. The statistical analysis proved that the Hypnosis Group had better results in the retest than the Control Group, especially in the rhythm test with F(1,28) = 25.60, p less than 0.0001. PMID- 2246112 TI - Mental status variation in a case of multiple sclerosis. AB - Various psychiatric symptoms have been described in patients with multiple sclerosis. The literature is reviewed, and it suggests that individual patients develop specific psychiatric syndromes. A case is presented with multiple psychiatric syndromes occurring within a single patient. PMID- 2246113 TI - Post traumatic stress disorder: an eclectic approach. AB - A number of victims of post traumatic stress disorder, apart from the rest of their symptom constellation, suffer flashbacks. These flashbacks occur during the waking state and frequently are very disabling. From among this group of patients, we have identified a few who demonstrate epileptiform discharge emanating from temporal lobe foci. We have postulated that indeed the flashbacks might represent an amalgam of abnormal neuronal firing along with the expression of a dynamically charged event. Eight cases are documented which illustrate this pattern. In all eight cases, the flashbacks were completely controlled through the use of anticonvulsant medication (carbamazepine and one case of valproate). Other symptoms were treated more traditionally. A modification to a conventional psychotherapeutic approach is introduced which does not merely foster abreaction but also introduces a process of desensitization to the highly charged events. The sessions during which the patient relives the precipitant to the syndrome are audiotaped. Following the experience of working through in therapy, the patient is encouraged to replay the tape(s) repeatedly over several months to facilitate flooding/desensitization. The two case summaries which are presented illustrate the integration of pharmacotherapeutic intervention, a focal short-term dynamic approach, and a behavioral model. PMID- 2246114 TI - Behavior of mitochondria in the living cell. PMID- 2246115 TI - Ultrastructural studies on the fertilization of mammalian gametes. PMID- 2246116 TI - Newt lung epithelial cells: cultivation, use, and advantages for biomedical research. PMID- 2246117 TI - Applications of bit-mapped "cognitive" potentials (ERPs) in clinical neurophysiology--CNV complex in patients with destruction of the dorso anteromedial bidirectional thalamo-prefrontal pathways. AB - We discuss the most important current problems relative to the recording procedures and methods of analysis, using inter alia spatio/temporal topographic maps, of some cognitive event-related potentials (CNV complex etc.) in normal and pathological conditions. After these initial premises of neurocognitive electrophysiology, we summarize the results for 8 patients in whom we examined the effects on CNV activity formation of surgical or spontaneous bihemispheric deafferentation of prefrontal/premotor cortical associative areas. These observations bear out the hypothesis that the bidirectional homohemispheric long and short distance pathways connecting associative parieto-temporal and occipital cortical areas to the prefrontal ones, play an important role in the genesis of the long-latency cognitive event-related potentials. PMID- 2246118 TI - Neuron specific enolase (NSE) and thymidine kinase (TK) as markers in biological fluids of brain tumor patients. AB - We studied the activity of two enzymes NSE and TK in the biological fluids of 104 patients with nervous system diseases, who fell into 4 groups. 20 subjects out of 35 in the tumor group had glial tumors. We fixed a cut-off value of NSE and TK activity at the 95th percentile of the control group, both in serum and in CSF. The aim of our investigation was to assess the reliability of TK and NSE assays in separating brain tumors from other neurological diseases. In our patients, most of the TK activity above the cut-off value was found in the tumor group. Serum TK seems to be a useful marker for following up cerebral tumors after surgery, but NSE is less useful for this purpose. PMID- 2246119 TI - The hypothalamus in MPTP-induced parkinsonism. AB - 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) has been shown to produce a parkinsonian syndrome in humans and other primates. Recent studies have demonstrated that in humans the hypothalamus has the highest binding density for (3H) MPTP, which corresponds to monoamine oxidase type B (MAO-B). There is evidence that the conversion of MPTP to the toxic compound MPP+ takes place in the hypothalamus; subsequently, MPP+ is transported to the striatal system, where destruction of nigrostriatal dopamine neurons occurs. Thus, the hypothalamus appears to be a primary target organ of MPTP toxicity. This assumption is supported by the observation that monkeys exposed to MPTP exhibit extensive pathological lesions in the hypothalamus which are manifested clinically by the development of life-threatening anorexia requiring forced feeding to overcome. We discuss the clinical implications of MPTP-induced hypothalamic damage to the pathophysiology of MPTP-induced parkinsonism and to Parkinson disease. It is suggested that consideration of hypothalamic involvement in MPTP-induced parkinsonism may provide a broader understanding of the pathophysiology of parkinsonism and may, in addition, account for the preliminary observations that MAO-B inhibitors retard the progression of Parkinson disease and possibly prolong life expectancy. PMID- 2246120 TI - Hallucinations in Parkinson disease: neuropsychological study. AB - Hallucinations occur fairly frequently in the course of the pharmacological treatment of Parkinson disease. Our aim in this study was to assess first the relation between hallucinations and mental deterioration and second the correlation between the perception disorder and the profile on the Minnesota Multiphasic Personality Inventory (MMPI). Of 304 parkinsonian subjects followed as outpatients at our center 27 (8.88%) had had hallucinations and 17 of these presented marked cognitive deficits (Mini Mental State less than 18) (62.9%) compared with 32 of the other 277 patients (11.5%) (X2 = 55.16, p less than 0.0001). A group of 9 patients who had had hallucinations and 10 controls who had not, all free from marked cognitive deficits, were assessed on the Luria-Nebraska Neuropsychological Battery (LNNB) and on the MMPI. The two groups did not differ significantly in respect of the LNNB but did in respect of the MMPI scales. On this evidence the frequency of mental deterioration is significantly higher in patients who have hallucinated. We discuss the meaning of the MMPI differences both from the biochemical angle and from that of personality factors. These data suggest that the MMPI might be useful for predicting hallucinations in undeteriorated parkinsonian patients on pharmacological therapy. PMID- 2246121 TI - Terguride in the treatment of Parkinson disease: preliminary experience. AB - Terguride, a partial DA-agonist with both dopaminergic and antidopaminergic properties, was tested in 11 PD patients in the "decompensated" phase of the disease, characterized by the presence of dyskinesias and motor fluctuations. Combined treatment of these patients with 1 mg/day of terguride and stabilized doses of levodopa reduced the severity and frequency of dyskinesias and motor fluctuations along with a slight but significant improvement of parkinsonian clinical picture. The "modulatory" effect of terguride on DA receptors, in this experimental conditions, is discussed. PMID- 2246122 TI - Clinical and electrophysiological findings in two cases of Miller Fisher syndrome. AB - Clinical, radiological and electrophysiological data in two patients with 'Miller Fisher syndrome' (MFS), characterized by ataxia, ophthalmoplegia and areflexia are reported. Of the many tests performed only the electrophysiological findings provided any clue to the site of the lesions and the structure involved, showing a significant pattern of brainstem dysfunction. The authors discuss the role of central and peripheral lesion theory in the light of these data and stress that electrophysiological findings lend considerable weight to the former and support the hypothesis that MFS should be recognize as a distinct clinical entity. PMID- 2246123 TI - Incidence of Chlamydia trachomatis infection related to selected signs and symptoms of lower genital tract infections in women. AB - Chlamydia trachomatis infections of the female reproductive tract is associated with a spectrum of clinical syndromes from simple colonization to mucopurulent cervicitis, urethritis, proctitis, and pelvic inflammatory disease. Its natural history and tendency for progression is unclear. It is said these infections are the most common of all sexually transmitted diseases. PMID- 2246124 TI - The appropriate use of technology (particularly in medical problems of the elderly). AB - Technology, particularly "high" technology, with little solid data, is often blamed for much of our increasing cost of health care. Politics and emotions are poor substitutes for accurate information needed for rational solutions. By targeting the desired outcome and studying the process needed to reach the outcome, we can make better decisions. The methods of designing, conducting and funding the studies needed to answer the difficult questions posed by the use of high technology in the elderly are available. Do we have the wisdom to use them? PMID- 2246125 TI - The 1988-1989 decubitus study. Can a standardization of treatment be set for the elderly patient with decubiti ulcers stage III? AB - On July 1, 1988, a 6-month study began which included 15 ICF and SNF facilities and a census of approximately 1,300 patients. Forms and instructions were sent to each facility prior to the study. Stage II to Stage IV decubiti ulcers were reported on a monthly basis. Information obtained on all decubiti included: Nutritional intake, mental state, mobility, incontinence, contributing diagnoses, decubiti sizes and locations, recurrence of decubiti sites, stages, dates healed, cultures taken and reported, and treatments given. The completed forms were mailed into the Decubitus Study Committee every 3 months being due October 1, 1988 and January 1, 1989. The forms were designed to be as brief as possible yet provide the desired information. PMID- 2246126 TI - Autonomy versus beneficence: the dilemma and its implications in home care. PMID- 2246127 TI - Functional assessments in home care. AB - The Popovich Scale holds great promise for use in home healthcare. Having established reliability and validity makes the tool valuable in promoting high quality nursing care at home. It is applicable to all older adults and their caregivers regardless of medical problems, nursing diagnoses, and regulatory agencies. PMID- 2246128 TI - Standardized care plans for home care. AB - Standardized Care Plans reflect the expected, accepted, normal nursing care and outcome of a patient with a specific diagnosis, problem, or condition. The patient's progress can therefore be evaluated against the expected outcome. PMID- 2246130 TI - A day in the life of a home health supervisor. PMID- 2246131 TI - "Just say no" to bad practice. PMID- 2246129 TI - Making an ethical decision in the home setting: the case of Stan. AB - Home health nurses are not immune to ethical dilemmas in their practices. In fact, the ethical dilemmas that are encountered in home health present a unique challenge to these nurses because of the relationship of the home care agency to the patient. PMID- 2246132 TI - What do we owe our aging parents? PMID- 2246133 TI - Law and ethics: never the twain shall meet? PMID- 2246134 TI - The ethical dilemmas. AB - This column has posed the issues and identified resources that home care nurses can use in an attempt to resolve the moral, social, economic, and professional factors that are confronted each day. Ethical dilemmas have been presented. The editor and I invite you to share your success (or lack of it) in resolving the issues you have experienced in caring for your patients. We look forward to hearing from you in an effort to benefit from your experiences. PMID- 2246135 TI - Whose life is it anyway? PMID- 2246136 TI - The dilemma of elder abuse. AB - The Alabama Protective Services Act of 1976 was designed to protect adults over 18 made vulnerable because of age, mental deficiency, or poor health. All practitioners of the healing arts are mandated to report if there is reasonable cause to believe abuse, neglect, or exploitation has occurred. PMID- 2246137 TI - Campylobacters associated with human diarrhoeal disease. PMID- 2246138 TI - Lactobacilli isolated from sugary kefir grains capable of polysaccharide production and minicell formation. AB - Homo- and heterofermentative species of Lactobacillus have been isolated from sugary kefir grains. Most of the homofermentative strains fermented tagatose and aldonitol and presented 48-54% of homology with Lactobacillus paracasei ssp. paracasei NCDO 151 (ex Lactobacillus casei). The two variants of a hetero fermentative species, although fermenting arabinose, were related to Lactobacillus hilgardii NCDO 264 (type strain) with 88% of homology. One of them produced polysaccharide from sucrose at pH 4.8 and 30 degrees C; the best glucose conversion into polysaccharide was obtained from 3% of sucrose (81.8%), and the maximum production occurred about 35 hours after the end of the log phase of growth, in MRS sucrose broth. Polysaccharide formation did not occur above 40 degrees C, a temperature at which no growth was observed. The two variants were forming minicells by abnormal divisions. PMID- 2246139 TI - Comparison of quantitative and qualitative methods of detecting hydrogen peroxide produced by human vaginal strains of lactobacilli. AB - A quantitative method was developed for the measurement of micromolar quantities of H2O2 produced in Rogosa broth and peptonized milk broth by vaginal strains of lactobacilli isolated from women. The production of substantial amounts reproducibly was dependent on the growth of the organisms in acid media (pH less than or equal to 6.0) under anaerobic or micro-aerophilic conditions with continuous agitation. The addition to the media of the enzyme inhibitor, 3-amino 1,2,4-triazole, with or without catalase sometimes induced the production of H2O2 especially in non-agitated cultures. However, other agents such as concanavalin and o-dianisidine had no enhancing effect, and catalase or peroxidase alone completely inhibited H2O2 production. The H2O2 produced in the acid media was stable for more than a month at 5 degrees C but not in media at pH greater than or equal to 7.0. Of five strains of lactobacilli tested by the quantitative method and by a chromogenic qualitative method (Rogosa-catalase or -per-oxidase agar), three consistently produced H2O2 measurable by the former method, but none did so after growth of the organisms on Rogosa-catalase/peroxidase agar which suggested that the qualitative method was unreliable. The fact that H2O2 was produced in substantial quantities by some strains and not at all by others enabled H2O2-producers and non-producers to be distinguished easily. PMID- 2246140 TI - Production of exotoxins by Aeromonas spp. at 5 degrees C. AB - The ability of 60 strains of Aeromonas to produce enterotoxin and haemolysin after cultivation at 5 degrees C for 7-10 d was investigated. The strains were isolated from lamb meat, offal, carcasses and faeces, and had previously been tested for their ability to produce these exotoxins at 37 degrees C. The results showed that some strains of Aeromonas hydrophila and A. sobria were capable of producing enterotoxin and haemolysin at 5 degrees C, but none of the A. caviae strains tested produced these two factors. Of the 30 A. hydrophila strains investigated 25 and 27 were enterotoxigenic and haemolytic respectively. Likewise, of the 24 A. sobria strains investigated 16 and 18 were enterotoxigenic and haemolytic respectively. The results indicate that certain strains of Aeromonas species, in particular A. hydrophila and A. sobria, are of potential public health significance in meats stored at refrigeration temperature. PMID- 2246141 TI - Open fronted safety cabinets in ventilated laboratories. AB - Open fronted Class I and II microbiological safety cabinets (MSCs) are required by the British Standard 5726 to provide similar levels of operator protection (viz. 10(5). In laboratories that are naturally ventilated large numbers of both types of cabinets have been shown to exceed this requirement consistently over a number of years. The designs of some mechanically ventilated laboratories, however, produce excessive turbulence and draughts that can prejudice containment at the front aperture. On-site commissioning tests to determine operator protection factor are now well established and are recognized as being essential to the setting up of all open fronted cabinets in both ventilated and unventilated laboratories. This paper shows that where environmental conditions induce unsatisfactory cabinet containment, adjustments to air supply and exhaust systems can be made which will enable both Class I and II cabinets to produce operator protection factors in excess of 10(5). When compatibility is achieved between the local environment and the cabinets it is demonstrated that disturbances at the front aperture, caused by operator working procedures or by disturbances due to personnel movement within the room, have similar effects on both Class I and II cabinets. Once performance levels have been satisfactorily achieved, regular containment testing has shown that consistent performance can be maintained. These aspects of open fronted safety cabinet performance are discussed in relation to ventilated laboratories suitable for work with the human immunodeficiency virus (HIV). Of paramount importance in the future is the necessity to design laboratory air systems that will be compatible with satisfactory safety cabinet performance--a relatively new requirement in ventilation system specifications. PMID- 2246142 TI - Heat shock protein synthesis and thermotolerance in Salmonella typhimurium. AB - The resistance of stationary phase Salmonella typhimurium to heating at 55 degrees C was greater in cells grown in nutritionally rich than in minimal media, but in all media tested resistance was enhanced by exposing cells to a primary heat shock at 48 degrees C. Chloramphenicol reduced the acquisition of thermotolerance in all media but did not completely prevent it in any. The onset of thermotolerance was accompanied by increased synthesis of major heat shock proteins of molecular weight about 83, 72, 64 and 25 kDa. When cells were shifted from 48 degrees C to 37 degrees C, however, thermotolerance was rapidly lost with no corresponding decrease in the levels of these proteins. There is thus no direct relationship between thermotolerance and the cellular content of the major heat shock proteins. One minor protein of molecular weight about 34 kDa disappeared rapidly following a temperature down-shift. Its presence in the cell was thus correlated with the thermotolerant state. PMID- 2246143 TI - Study of haemolytic activity of some Campylobacter spp. on blood agar plates. AB - A total of 152 strains of Campylobacter jejuni, C. coli, C. laridis and C. fetus subsp. fetus were tested for haemolysis on blood agar plates. Distinct haemolysis was detected in 92.3% (96/104) of strains of C. jejuni and 21.7% (5/23) of strains of C. coli on sheep blood heart infusion agar after incubation for 4 d microaerobically at 42 degrees C. Haemolysis was also detected on horse blood heart infusion agar. Haemolysis was not detected at 37 degrees C except with one of 50 strains of C. jejuni tested at this temperature, which was weakly positive. Campylobacter laridis was not haemolytic; C. fetus subsp. fetus, which does not grow at 42 degrees C, showed no haemolysis at 37 degrees C. Blood agar (Oxoid, BA Base No. 2) was not suitable for testing for haemolysis by these organisms. A microaerobic gas mixture containing hydrogen is better than that containing nitrogen because the medium has a brighter colour, making haemolysis easier to detect. There was no synergistic haemolysis with Staphylococcus aureus or Streptococcus agalactiae. The plate haemolysis test as described here may aid differentiation within the thermophilic campylobacters. PMID- 2246144 TI - The influence of pH, temperature and organic acids on the initiation of growth of Yersinia enterocolitica. AB - The influence of incubation temperature, and of acetic, lactic and citric acids on the minimum pH for the initiation of growth of six strains of Yersinia enterocolitica was determined. The strains included two of serotype O : 9, two of serotype O : 3, and one each of serotypes O : 8 and O : 5, 27. In a culture medium acidified with HCl to pH values between 4.0 and 6.0 at intervals of approximately 0.1 unit the minimum pH at which growth was detected after incubation at 20 degrees, 10 degrees, 7 degrees and 4 degrees C for 21 d was in the ranges 4.18-4.36, 4.26-4.50, 4.36-4.83 and 4.42-4.80, respectively. The minimum pH for growth was also determined in media that contained 17, 33 and 50 mmol/l acetic acid adjusted to pH values between 5.1 and 5.9 at intervals of approximately 0.2 unit, 24, 48 and 95 mmol/l citric acid adjusted to pH values between 4.1 and 4.9 at intervals of approximately 0.2 unit, and 22, 44, and 111 mmol/l lactic acid adjusted to pH values between 4.3 and 5.7 at intervals of approximately 0.4 or 0.5 unit. The effect of these concentrations of organic acids was, in most cases, to increase the minimum pH that allowed growth. The order of effectiveness of the organic acids in raising the minimum pH for growth was acetic greater than lactic greater than citric and the minimum inhibitory concentrations were greater at higher temperatures. PMID- 2246145 TI - Effect of growth conditions and storage on the specific activity of beta lactamases of Bacteroides spp. AB - The influences of growth conditions and cold storage on the specific activity of beta-lactamases of four strains of Bacteroides spp. was studied. Interbatch variation was observed in extracts prepared in an identical way on separate occasions but less variation was observed in extracts prepared from bacteria grown on Brain Heart Infusion agar supplemented with yeast extract, haemin and menadione, than in similar extracts of bacteria grown in broth or on other solid media. The loss of enzyme activity seen during the stationary phase of growth of some strains in broth was minimal during incubation for 48 h on agar. Storage of enzyme extracts at 4 degrees C was associated with loss of enzyme activity, but activity was retained during storage at -70 degrees C for up to 32 days. Freezing and thawing had little effect on enzyme activity. PMID- 2246146 TI - Numerical analysis of electrophoretic protein patterns of Morganella morganii strains from faeces, wound, urine and other clinical sources. AB - Sixty-five strains of Morganella morganii (mainly of human origin) were characterized by one-dimensional SDS-PAGE of cellular proteins. The strains came from various countries; 13 were from stools (including one from a toucan), 13 from wounds, 11 from urine, five from blood (including one from a snake), five from the respiratory tract (four sputum, one lung), 12 from miscellaneous sources and six from unknown sources. The protein patterns, which contained 45 to 50 discrete bands, were highly reproducible. The patterns of 67 M. morganii cultures plus those of the type strains of seven Proteus and Providencia species were used as the basis for two numerical analyses. In the first, which included all the protein bands, the M. morganii strains formed 21 clusters at the 91% S level. In the second analysis, in which the principal protein bands (in the 31.6-43.2 kDa range) were excluded, the 67 M. morganii cultures formed a single cluster at the 80% S level distinct from the seven Proteus and Providencia reference strains. We conclude that high resolution PAGE combined with computerized analysis of protein patterns provides the basis for typing clinical strains of M. morganii. Reference strains of each of the 21 PAGE types identified are available from NCTC for inclusion in future studies. PMID- 2246147 TI - The effect of terrestrial effluents on the incidence of Aeromonas spp. in coastal waters. AB - The numbers of Aeromonas species were monitored for one year at 18 stations on the Barcelona coast. Their concentrations exceed those of faecal coliforms and faecal streptococci in all samples, both on the shoreline and at 500 m from the coast. The mean values of the three bacterial counts reflected the proximity of the terrestrial effluents. There was a positive correlation between aeromonads and faecal indicators on the shoreline but not at 500 m offshore. This reflected their common origin and different survival rates in seawater. When sterile sea water was inoculated with A. hydrophila ATCC 7966, the numbers decreased initially by three orders of magnitude before they began to multiply. The final count was related to the concentration of organic matter in the water. PMID- 2246148 TI - Late pulmonary allergic responses in actively but not passively IgE-sensitized rats. AB - Previous studies suggested that although rats that were passively sensitized [monoclonal murine immunoglobulin E (IgE)] would respond to pulmonary antigen challenge with an immediate increase in resistance, they exhibited no late increases in resistance, unlike late changes in rats actively sensitized to preferentially produce IgE antibody. We hypothesized that passively sensitized rats also would not develop antigen-induced pulmonary inflammation. In a blinded protocol we compared immediate responses and pulmonary resistance and inflammation at 8, 19 and 24 h after challenge with placebo antigen, with dinitrophenol-bovine serum albumin (DNP-BSA) to elicit a passively sensitized response, or with ovalbumin (OA) to elicit an actively sensitized response. Despite similar immediate responses to OA and DNP-BSA, only the rats challenged with OA had marked inflammatory changes and a significant incidence of late elevations in resistance. Inflammation scores and lung resistance were significantly correlated only in the OA group. We also observed that anesthesia with fentanyl/droperidol significantly attenuated the immediate but not the late responses to antigen challenge, compared with rats anesthetized with ketamine. We conclude that IgE-mediated immediate responses to pulmonary antigen challenge are insufficient, and may be unnecessary, to initiate antigen-induced late inflammatory changes. PMID- 2246149 TI - Segmental vascular resistance in postobstructive pulmonary vasculopathy. AB - Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones. PMID- 2246150 TI - Effects of elastic loading on porcine trachealis muscle mechanics. AB - To shorten in vivo, airway smooth muscle must overcome an elastic load provided by cartilage and lung parenchyma. We examined the effects of linear elastic loads (0.2-80 g/cm) on the active changes in porcine trachealis muscle length and tension in response to electrical field stimulation in vitro. Increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening while causing an increase in tension generation of muscle strips stimulated by electrical field stimulation. Shortening was decreased by 50% at a load of 8 g/cm. At small elastic loads (less than or equal to 1 g/cm) contractile responses approximated isotonic responses (shortening approximately 60% of starting length), whereas at large loads (20 g/cm) responses approximated isometric responses with minimal shortening (20%). We conclude that elastic loading significantly alters the mechanical properties of airway smooth muscle in vitro, effects that are likely relevant to the loads against which the smooth muscle must contract in vivo. PMID- 2246151 TI - Muscle blood flow and muscle metabolism during exercise and heat stress. AB - The effect of heat stress on blood flow and metabolism in an exercising leg was studied in seven subjects walking uphill (12-17%) at 5 km/h on a treadmill for 90 min or until exhaustion. The first 30 min of exercise were performed in a cool environment (18-21 degrees C); then subjects moved to an adjacent room at 40 degrees C and continued to exercise at the same speed and inclination for a further 60 min or to exhaustion, whichever occurred first. The rate of O2 consumption, 2.6 l/min (1.8-3.3) (average from cool and hot conditions), corresponded to 55-77% of their individual maximums. In the cool environment a steady state was reached at 30 min. When the subjects were shifted to the hot room, the core temperature and heart rate started to rise and reached values greater than 39 degrees C and near-maximal values, respectively, at the termination of the exercise. The leg blood flow (thermodilution method), femoral arteriovenous O2 difference, and consequently leg O2 consumption were unchanged in the hot compared with the cool condition. There was no increase in release of lactate and no reduction in glucose and free net fatty acid uptake in the exercising leg in the heat. Furthermore, the rate of glycogen utilization in the gastrocnemius muscle was not elevated in the hot environment. There was a tendency for cardiac output to increase in the heat (mean 15.2 to 18.4 l/min), which may have contributed to the increase in skin circulation, together with a possible further reduction in flow to other vascular beds, because muscle blood flow was not reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246152 TI - A comparison of changes in esophageal pressure and regional juxtacardiac pressures. AB - The relationship between esophageal pressure and juxtacardiac pressures was studied during positive end-expiratory pressure (PEEP) ventilation applied to both lungs or selectively to one lung. The experiments were performed in eight anesthetized dogs with balloon catheters in the esophagus and in the left and right pericardial and overlying pleural cavities and with an open-ended liquid filled catheter in the pleural cavity. Bilateral PEEP (10, 20, and 30 cmH2O) caused progressive and similar increments in left and right pleural pressure. Selective PEEP, however, increased ipsilateral pleural balloon pressure more than contralateral pressure. The increase in ipsilateral pleural balloon pressure markedly exceeded the increase in esophageal pressure. There was a small increase in pleural open-ended catheter pressure that approximated the increase in esophageal pressure. During selective PEEP, pericardial balloon pressure remained uniform because of a decrease in ipsilateral pericardial transmural pressure. In conclusion, selective PEEP caused nonuniform increments in regional pleural balloon pressure. Left and right pericardial balloon pressure, however, increased uniformly with selective PEEP because of reduced ipsilateral pericardial transmural pressure. The esophageal balloon did not reflect the marked regional increments in pleural balloon pressure with selective PEEP and consistently underestimated the changes in pleural balloon pressure with general PEEP. PMID- 2246153 TI - Glucocorticoid-induced muscle atrophy prevention by exercise in fast-twitch fibers. AB - Exercise has been shown to be effective in preventing glucocorticoid-induced atrophy in muscles containing high proportions of type II or fast-twitch fibers. This investigation was undertaken to further evaluate this response in type IIa and IIb fibers, determined by histochemical staining for myofibrillar adenosinetriphosphatase with alkaline and acid preincubation. Steroid [cortisol acetate (CA), 100 mg/kg body wt] and exercise (running 90 min/day, 29 m/min) treatments were initiated simultaneously for 11 consecutive days in female rats. Fiber distribution and area measurements were performed in a deep and superficial region of plantaris muscle. The exercise regimen spared approximately 40% of the CA-induced plantaris muscle atrophy. In the deep region, the fiber population, which contained approximately 13% type I (slow-twitch), 24% type IIa, and 63% IIb fibers, was not affected by either treatment. In the superficial section, which consisted solely of type II fibers, the proportion of type IIa fibers was higher (27 vs. 9%, P less than 0.01) in the steroid- than in the vehicle-treated groups. Within each region, type IIa fibers were less susceptible to atrophy than type IIb fibers, and within each fiber type, the deep region had less atrophy than the superficial region. Type I fibers were unchanged by steroid treatment. For type IIa fibers, exercise prevented 100% of the atrophy in the deep region and 50% in the superficial region. For type IIb fibers, the activity spared 67 and 40% of the atrophy in these same regions, respectively. These results show that glucocorticoids are capable of changing the myosin phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246154 TI - Effect of airway and left atrial pressures on microcirculation of newborn lungs. AB - To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions. PMID- 2246155 TI - Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats. AB - Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient. PMID- 2246156 TI - Stress adaptation and low-frequency impedance of rat lungs. AB - At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246157 TI - Control of total peripheral resistance during hyperthermia in rats. AB - To elucidate the effect of blood volume on the circulatory adjustment to heat stress, we studied alpha-chloralose-anesthetized rats at three levels of blood volume: normovolemia (NBV), hypervolemia (HBV; +32% plasma volume by isotonic albumin solution infusion), and hypovolemia (LBV; -16% plasma volume by furosemide administration). Body surface heating was performed with an infrared lamp to raise arterial blood temperature (Tb) at the rate of approximately 0.1 degree C/min. Before heating, central venous pressure (CVP) was significantly higher in HBV (0.41 +/- 0.25 mmHg) and lower in LBV (-1.44 +/- 0.22 mmHg) than in NBV (-0.41 +/- 0.10 mmHg). The Tb at which CVP started to decrease was approximately 40 degrees C in HBV, approximately 41 degrees C in NBV, and approximately 42 degrees C in LBV, and it decreased by 1.53 +/- 0.14, 1.92 +/- 0.24, and 0.62 +/- 0.14 mmHg from 37 to 43 degrees C of Tb in HBV, NBV, and LBV, respectively. Stroke volume was closely correlated with CVP, and this relationship was not affected by Tb. Heart rate responses to the raised Tb were similar among the three groups. Mean arterial pressure (MAP) was not affected by blood volume modification or CVP and was maintained at preheating (Tb 37 degrees C) level until Tb rose to 40 degrees C. Above this Tb, MAP increased until Tb reached 43 degrees C (+30-40 mmHg) for all three groups. Total peripheral resistance (TPR) was inversely correlated with CVP, and the slope of the linear relationship between TPR and CVP in LBV was three- to fourfold steeper than in NBV or HBV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246158 TI - Depression of posttetanic twitch potentiation by low calcium and calcium channel antagonists. AB - The purpose of this investigation was to determine if antagonizing extracellular calcium influx altered posttetanic twitch potentiation (PTP). Whole muscles and muscle fiber bundles (less than or equal to 25 fibers) dissected from frog sartorius and semitendinosus muscles were mounted at optimal length in a normal Ringer solution (NR). To determine PTP, isometric twitches were evoked every 10 s (0.1 Hz) before and after a 2.5-s tetanic contraction (80 Hz). To antagonize calcium influx, low-calcium Ringer [LCR, calcium replaced by 3 mM magnesium and 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], NR plus diltiazem (Dilt, 30 microM), NR plus nifedipine (Nif, 10 microM), and NR plus D 600 (30 microM) were also used (n = 8 for each condition). These conditions altered pretetanic twitch tension by only -1.2 +/- 2.4, 4.2 +/- 2.3, 4.7 +/- 3.7, and 1.6 +/- 3.7% (SE), (LCR, Dilt, Nif, and D 600, P greater than 0.05) but caused a noticeable decrease in tension at the end of the tetanus. Under NR conditions, twitches evoked immediately after the tetanus were potentiated by 49.5 +/- 0.4% with the peak rate of tension development (dP/dt) increased by 44.9 +/- 0.5% (P less than 0.05). Antagonizing calcium influx depressed the PTP response by 59.8 +/- 6.2, 55.9 +/- 10.1, 73.2 +/- 6.8, and 29.8 +/- 3.6% (P less than 0.05) and increased dP/dt by 65.8 +/- 11.1, 45.7 +/- 8.6, 55.6 +/- 4.4% and 49.0 +/- 10.5% (P less than 0.05). Addition of drugs immediately after the tetanus only slightly reduced PTP but accelerated recovery of the twitch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246159 TI - Endogenous opioid effects on abdominal muscle activity during inspiratory loading. AB - In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l 1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246160 TI - Leaky intra-acinar arteries in rat lungs perfused with hydrogen peroxide. AB - We have investigated the effects of H2O2 (150 or 300 microM) on the ultrastructure and permeability of the pulmonary endothelium in rat lungs perfused for 60 min with buffered Hanks' bovine serum albumin medium. In one group of experiments, we examined the effect of H2O2 on the uptake and transport of cationized ferritin (CF) by endothelial cells in intra-acinar arteries, alveolar capillaries, and interlobular veins. The influence of the oxidant on endothelial adsorptive endocytic processes was assessed by measuring the density of ferritin particles in luminal vesicles, multivesicular bodies, and basal lamina. In a second group of experiments, we examined the effects of H2O2 on the fine structure and permeability to electron-dense macromolecules of arterial, microvascular, and venous endothelium. For this purpose, at the end of the 60-min perfusion with H2O2, CF was perfused to identify leaky vessels. We found that H2O2 caused a dose-dependent inhibition of transcytosis of CF in all vascular segments. At the lower dose of H2O2, inhibition of transcytotic activity was not associated with structural injury to the vascular endothelium or with elevation of wet-to-dry ratios. At the higher oxidant dose, inhibition of transcytosis was associated with leaky arterial endothelium and elevation of wet-to-dry ratios (6.44 +/- 0.12 vs. 5.64 +/- 0.16, P less than 0.02). The effects of H2)2 were prevented by adding catalase to the perfusate. The selective loss of structural integrity and leakiness of the arterial endothelium were diminished but not completely abolished by perfusing the oxidant retrograde from the venous side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246161 TI - Perceptual cues used to reproduce an inspired lung volume. AB - The perceptual cues used to reproduce a specific lung volume were studied in five healthy males. Performance was examined under three conditions that were designed progressively to remove the reliability of cues that a subject might use to duplicate a specific lung volume. As judged by the mean errors (disregarding the sign of the error) and constant errors (including the sign of the error), there were no significant differences in the accuracy with which subjects reproduced a standard volume, even when they were required to perform the reproductions at various inspiratory rates and starting volumes. The best performance was in the final experimental session in which the mean error for the group, all conditions combined, was 133 ml. There was a difference between conditions on the just noticeable differences (a measure of variability including the sign of the error); subject performance was significantly more variable when the inspiratory flow rate was altered. The group mean error for the final session for just noticeable differences was 93.3 ml. Our results indicate that a specific lung volume can be achieved using cues other than those associated with the movement made to attain that lung volume. The specific afferents that provided these cues are not known, but we propose that they uniquely signal static position. PMID- 2246162 TI - Roles of absolute and relative load in skin vasoconstrictor responses to exercise. AB - Systemic hemodynamic responses to exercise (e.g., heart rate, blood pressure) depend on the relative intensity, the active muscle mass, and the mode of exercise. It is not known whether regional vasomotor responses follow the same pattern. To answer this question, in five men we examined cutaneous vascular responses to dynamic and isometric exercise of two legs, one leg, one arm, and one hand, each at high and low work loads. Skin blood flow was monitored by laser Doppler flowmetry (LDF) at the forearm. Mean arterial pressure (MAP) was measured each minute. Cutaneous vascular conductance (CVC) was indexed as LDF/MAP. Reductions in CVC during the 1st min of dynamic exercise were statistically significant for two-leg exercise at either level and for one-leg exercise at the higher level. Dynamic exercise of smaller muscle groups at either intensity was not associated with significant changes in CVC. The reduction in CVC correlated with external work load (r = 0.75). Work load relative to the capacity of a given muscle group had no identifiable role in the response of CVC to dynamic exercise but did have a role in the increase in MAP at the beginning of exercise. Isometric exercise did not have a measurable effect on CVC regardless of the muscle group or the intensity of the exercise. We conclude that the level of external work determines the redistribution of blood flow from skin to active muscle. Furthermore, absolute rather than relative work and dynamic rather than isometric modes of exercise are the dominant factors. PMID- 2246163 TI - Succinylcholine potentiates responses to intravenous acetylcholine in the canine lung periphery. AB - Using the wedged bronchoscope technique to measure collateral resistance (Rcs), we evaluated the effect of succinylcholine (SCh) on the response to acetylcholine (ACh) and methacholine (MCh) in the lung periphery in six mongrel dogs. Dogs were anesthetized, intubated, and mechanically ventilated. After a stable baseline Rcs was obtained, responses to intravenous ACh (25-200 micrograms), intravenous MCh (3-30 micrograms), and aerosolized ACh (30-100 micrograms/ml for 15 s) were measured. We compared the Rcs responses with 1) ACh alone, 2) ACh 2 min after SCh (0.5 mg/kg), 3) ACh 2 min after SCh and during hexamethonium infusion (5 mg/kg + 10 mg.kg-1.h-1), 4) MCh 2 min after SCh, and 5) ACh aerosol 2 min after SCh. SCh did not significantly alter baseline airway tone. SCh increased the Rcs response to ACh by 48 +/- 17% (SE) (P less than 0.01). SCh in the presence of hexamethonium increased the Rcs response by 10 +/- 3% (P less than 0.05), while hexamethonium itself increased the response to ACh by 69 +/- 27%. Because SCh did not increase the Rcs response to intravenous MCh or to aerosolized ACh, SCh probably enhances airway reactivity to intravenous ACh by competing for pseudocholinesterase in plasma. We conclude that the level of muscle relaxant must be taken into account in interpreting studies of airway reactivity when intravenous ACh is employed. PMID- 2246164 TI - Altered function of pulmonary surfactant in fatty acid lung injury. AB - To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids. PMID- 2246165 TI - Metabolic effects of training in humans: a 31P-MRS study. AB - The purpose of this study was to determine the feasibility of measuring with 31P nuclear magnetic resonance the effects of an endurance training program on the high-energy phosphate metabolism of exercising human skeletal muscle. The system used included a 1.9-T 30-cm-bore Oxford Systems superconducting magnet, a PhosphoEnergetics spectrometer, and a modified Cybex isokinetic ergometer. Seven healthy human volunteers exercised their wrist flexor muscles 20 min/day 5 days/wk for 8 wk. Testing before and after the training period consisted of a performance test to measure muscle functional capacity and a ramp test to measure the work-energy cost relationship of the exercising muscles. The results indicate that the subjects had a significant increase in their work output on the 10-min performance test after training. They also exhibited an increase in the work energy cost relationship on the ramp test as indicated by a decrease in peak Pi to-phosphocreatine ratio and an increase in pH at the same relative power output after training. These results indicate that 1) the training program was sufficient to elicit a training effect and 2) this effect was observed with 31P nuclear magnetic resonance as an increased potential for oxidative metabolism, particularly at the high exercise levels. PMID- 2246166 TI - Modeling human performance in running. AB - This paper focuses on the characteristics of a model interpreting the effect of training on athletic performance. The model theory is presented both mathematically and graphically. In the model, a systematically quantified impulse of training produces dual responses: fitness and fatigue. In the absence of training, both decay exponentially with time. With repetitive training, these responses satisfy individual recurrence equations. Fitness and fatigue are combined in a simple linear difference equation to predict performance levels appropriate to the intensity of training being undertaken. Significant observed correlation of model-predicted performance with a measure of actual performance during both training and tapering provides validation of the model for athletes and nonathletes alike. This enables specific model parameters to be estimated and can be used to optimize future training regimens for any individual. PMID- 2246167 TI - Pulmonary blood volume and edema in postpneumonectomy lung growth in rats. AB - After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain. PMID- 2246168 TI - Membrane and cellular properties in oscillating networks: implications for respiration. AB - Because of a number of major advances in the past one to two decades, there is little doubt that the inherent cellular and membrane properties of neurons in an oscillating network play an important role in shaping the output of that network. There are a number of such examples in vertebrate and invertebrate systems. In this review, we present some of the newer methods that have been used in the identification of membrane properties and detail some cellular studies performed in both vertebrate (locomotion and sleep/waking rhythms) and invertebrate network systems (escape swimming in Tritonia diomedia and pyloric rhythm in Panulirus interruptus). Studies examining the cellular or membrane properties of respiratory neurons have been scarce until recently. The importance of these properties in dictating respiratory rhythm generation and output in the mature and immature animal is not yet known; however, we put this issue in perspective by building a parallel between mammalian respiration and other vertebrate networks that have been better investigated and characterized. PMID- 2246169 TI - Physiology of aging related to outcome in the adult respiratory distress syndrome. AB - Thirty-nine patients with adult respiratory distress syndrome (ARDS) were enrolled in a study to identify potential age-related changes in organ system function that may help explain the apparent association between age and poor outcome in these patients. Criteria for enrollment included an arterial PO2-to inspired O2 concentration ratio less than or equal to 200 in a clinical setting consistent with ARDS. Patients were excluded if they were less than 18 yr old, had clinical manifestations of congestive heart failure, were seropositive for the human immunodeficiency virus, or had stage II metastatic lung cancer. Patients were divided into two groups: those less than 60 yr old (mean 42 +/- 3 yr, n = 17) and those greater than or equal to 60 yr old (73 +/- 2 yr, n = 16). A group of six patients was analyzed as a separate subset based on a body temperature less than or equal to 97.5 degrees F at enrollment (hypothermic patients, 73 +/- 4 yr old). Sepsis was present in 67% of the nonhypothermic patients and in all the hypothermic patients. Mortality rates were 12% in the patients less than 60 yr and 69% in the nonhypothermic patients greater than or equal to 60 yr. All the hypothermic patients died. Sequential data obtained over 6 days were compared within and between groups. The following results were obtained. 1) The ratio of arterial PO2 to inspired O2 fraction was greater and the positive end-expiratory pressure used was significantly less in the patients greater than or equal to 60 yr old compared with the younger group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246171 TI - Effect of left atrial pressure on bronchial vascular hemodynamics. AB - We studied the bronchial vascular response to downstream pressure elevation by increasing left atrial pressure (Pla) and mean airway pressure (Paw) with positive end-expiratory pressure (PEEP). In seven pentobarbital-anesthetized ventilated sheep, we cannulated and perfused the bronchial branch of the bronchoesophageal artery. Steady-state bronchial artery pressure- (Pba) flow (Qba) relationships were obtained as Pla was increased by inflating a balloon catheter in the left atrium. Bronchial vascular resistance (BVR), determined by the inverse slope of the Pba-Qba relationship, increased significantly from 3.2 +/- 0.3 (SE) mmHg.ml-1.min-1 at a Pla of 2.9 +/- 0.7 mmHg to 5.1 +/- 0.5 mmHg.ml 1.min-1 at a Pla of 20.1 +/- 2.0 mmHg (P = 0.0007). Under control Qba (23.3 +/- 1.2 ml/min), these changes in BVR represent a 3.6 +/- 0.7-mmHg increase in Pba per mmHg increase in Pla. The zero-flow pressure increased 1.3 +/- 0.2 mmHg/mmHg increase in Pla. After infusion of papaverine, a smooth muscle paralytic agent, directly into the bronchial artery, BVR decreased significantly to 1.3 +/- 0.7 mmHg.ml-1.min-1 (P = 0.0004). Under these dilated conditions, BVR was unaltered by increases in Pla. After papaverine administration, Pba increased 0.9 +/- 0.1 and 1.2 +/- 0.1 mmHg/mmHg increase in Pla during control and zero-flow conditions, respectively. Thus the effect of Pla elevation on BVR appears to be dependent on active smooth muscle responses. Paw elevation had similar effects on Pba. Under control Qba, Pba increased 2.2 +/- 0.4 mmHg/mmHg increase in Paw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246170 TI - Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood. AB - In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246172 TI - A model of the mechanics of airway narrowing. AB - To examine the interaction between airway smooth muscle shortening and airway wall thickening on changes in pulmonary resistance, we have developed a model of the tracheobronchial tree that allows simulation of the mechanisms involved in airway narrowing. The model is based on the symmetrical dichotomous branching tracheobronchial tree as described by Weibel and uses fluid dynamic equations proposed by Pedley et al. to calculate inspiratory resistance during quiet tidal breathing. To allow for changes in lung volume, we used the airway pressure-area curves developed by Lambert et al. The model is easily implemented with a spreadsheet and personal computer that allows calculation of total and regional pulmonary resistance. At each airway generation in the model, provision is made for airway wall thickness, the maximal airway smooth muscle shortening achievable, and an S-shaped dose-response relationship to describe smooth muscle shortening. To test the validity of the model, we compared pressure-flow curves generated with the model with measurements of pulmonary resistance while normal subjects breathed air and 20% O2-80% He at a variety of lung volumes. By simulating progressive airway smooth muscle shortening, realistic pulmonary resistance vs. dose-response curves were produced. We conclude that this model provides realistic estimates of pulmonary resistance and shows potential for examining the various mechanisms that could produce excessive airway narrowing in disease. PMID- 2246173 TI - Mechanical deficit persists during long-term muscle hypertrophy. AB - Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production. PMID- 2246174 TI - Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects. AB - Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects. PMID- 2246175 TI - Effect of thromboxane antagonists on ozone-induced airway responses in dogs. AB - Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L 655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h 1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness. PMID- 2246176 TI - Measurement of the body composition of living gray seals by hydrogen isotope dilution. AB - The body composition of living gray seals (Halichoerus grypus) can be accurately predicted from a two-step model that involves measurement of total body water (TBW) by 2H or 3H dilution and application of predictive relationships between body components and TBW that were derived empirically by slaughter chemical analysis. TBW was overestimated by both 2HHO and 3HHO dilution; mean overestimates were 2.8 +/- 0.9% (SE) with 2H and 4.0 +/- 0.6% with 3H. The relationships for prediction of total body fat (TBF), protein (TBP), gross energy (TBGE), and ash (TBA) were as follows: %TBF = 105.1 - 1.47 (%TBW); %TBP = 0.42 (%TBW) - 4.75; TBGE (MJ) = 40.8 (mass in kg) - 48.5 (TBW in kg) - 0.4; and TBA (kg) = 0.1 - 0.008 (mass in kg) + 0.05 (TBW in kg). These relationships are applicable to gray seals of both sexes over a wide range of age and body conditions, and they predict the body composition of gray seals more accurately than the predictive equations derived from ringed seals (Pusa hispida) (Stirling et al., Can. J. Zool. 53: 1021-1027, 1975) and from the equation of Pace and Rathbun (J. Biol. Chem. 158: 685-691, 1945), which has been reported to be generally applicable to mammals. PMID- 2246177 TI - Myoglobin content and citrate synthase activity in different parts of the normal human heart. AB - Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2. PMID- 2246178 TI - Human dose-response relationship for decompression and endogenous bubble formation. AB - The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections. PMID- 2246179 TI - Regulation of phosphorylase a activity in human skeletal muscle. AB - The control mechanism of glycogenolysis by phosphorylase a in contracting muscle has been investigated. The quadriceps femoris muscles of six subjects were intermittently stimulated at 15 and 50 Hz. The stimulation lasted 9.6 s and was performed twice at 15 Hz and once at 50 Hz. Epinephrine was infused continuously during the experiment. The force generation and ATP turnover rate were nearly twofold higher at 50 Hz than at 15 Hz. Calculated mean Pi was 5.7 and 10.0 mM during the two 15-Hz stimulations and 8.1 mM during the 50-Hz stimulation. Phosphorylase a varied between 85.5 and 91.5% without significant differences between periods. However, the rate of glycogenolysis was twofold higher during the stimulation at 50 Hz than it was at 15 Hz (P less than 0.05) and was related to the ATP turnover rate (r = 0.992). These results demonstrate that rapid glycogen breakdown during muscle contraction cannot be solely explained by transformation of phosphorylase b to a and increased Pi concentration. The contraction intensity may determine the glycogenolytic rate through a transient increase in free AMP level related to the ATP turnover rate. PMID- 2246180 TI - Experimental cardiac tamponade: correlation of pressure, flow velocity, and echocardiographic changes. AB - Seven episodes of experimental cardiac tamponade were induced in five anesthetized closed-chest dogs. Simultaneous pericardial and intracavitary pressures were synchronized with superior vena caval and transvalvular pulsed Doppler flow tracings. The earliest indication of tamponade was the development of a negative transmural right atrial pressure that occurred during early ventricular diastole and was associated with echocardiographic evidence of right atrial collapse. This was also associated with reversal of diastolic flow in the superior vena cava and with diminished early diastolic flow velocity across the tricuspid as well as the mitral valve. During more advanced cardiac tamponade, the transmural right atrial pressure became negative during both early and late ventricular diastole as well as during isovolumic ventricular systole. This was associated with a disappearance of early diastolic ventricular filling and right ventricular diastolic collapse as observed on two-dimensional echocardiography. In hypotensive cardiac tamponade (cardiac output diminished by 70%), the decreased transmural right atrial pressure that developed during ventricular systole was accompanied by diminished antegrade flow in the superior vena cava. In advanced and hypotensive tamponade, ventricular filling occurred mainly during atrial contraction. PMID- 2246181 TI - Splenic contraction during breath-hold diving in the Korean ama. AB - Major increases of hemoglobin concentration and hematocrit, possibly secondary to splenic contraction, have been noted during diving in the Weddell seal. We sought to learn whether this component of the diving response could be present in professional human breath-hold divers. Splenic size was measured ultrasonically before and after repetitive breath-hold dives to approximately 6-m depth in ten Korean ama (diving women) and in three Japanese male divers who did not routinely practice breath-hold diving. Venous hemoglobin concentration and hematocrit were measured in nine of the ama and all Japanese divers. In the ama, splenic length and width were reduced after diving (P = 0.0007 and 0.0005, respectively) and calculated splenic volume decreased 19.5 +/- 8.7% (mean +/- SD, P = 0.0002). Hemoglobin concentration and hematocrit increased 9.5 +/- 5.9% (P = 0.0009) and 10.5 +/- 4% (P = 0.0001), respectively. In Japanese male divers, splenic size and hematocrit were unaffected by repetitive breath-hold diving and hemoglobin concentration increased only slightly over baseline (3.0 +/- 0.6%, P = 0.0198). Splenic contraction and increased hematocrit occur during breath-hold diving in the Korean ama. PMID- 2246182 TI - Alveolar slope and dead space of He and SF6 in dogs: comparison of airway and venous loading. AB - Series (Fowler) dead space (VD) and slope of the alveolar plateau of two inert gases (He and SF6) with similar blood-gas partition coefficients (approximately 0.01) but different diffusivities were analyzed in 10 anesthetized paralyzed mechanically ventilated dogs (mean body wt 20 kg). Single-breath constant-flow expirograms were simultaneously recorded in two conditions: 1) after equilibration of lung gas with the inert gases at tracer concentrations [airway loading (AL)] and 2) during steady-state elimination of the inert gases continuously introduced into venous blood by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)]. VD was consistently larger for SF6 than for He, but there was no difference between AL and VL. The relative alveolar slope, defined as increment of partial pressure per increment of expired volume and normalized to mixed expired-inspired partial pressure difference, was larger by a factor of two in VL than in AL for both He and SF6. The He-to-SF6 ratio of relative alveolar slope was generally smaller than unity in both VL and AL. Whereas unequal ventilation-volume distribution combined with sequential emptying of parallel lung regions appears to be responsible for the sloping alveolar plateau during AL, the steeper slope during VL is attributed to the combined effects of continuing gas exchange and ventilation-perfusion inequality coupled with sequential emptying. The differences between He and SF6 point at the contributing role of diffusion-dependent mechanisms in intrapulmonary gas mixing. PMID- 2246183 TI - Comparison of phenylephrine bolus and infusion methods in baroreflex measurements. AB - Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects. PMID- 2246184 TI - Muscle buffer capacity estimated from pH changes during rest-to-work transitions. AB - Gated phosphorus nuclear magnetic resonance (31P-NMR) spectra were acquired after 5 or 9 s of 5-Hz stimulation in rat and cat skeletal muscles, respectively. Net phosphocreatine (PCr) hydrolysis was associated with an intracellular alkalinization of 0.08 +/- 0.01 and 0.05 +/- 0.003 pH units in isolated perfused cat biceps and soleus, respectively, and 0.12 +/- 0.02 in the superficial predominantly fast-twitch white portion of gastrocnemius of anesthetized rats. The net change in [H+] expected from PCr hydrolysis was calculated, and apparent buffer capacity (beta) in intact muscles was calculated from beta = delta [H+]/delta pH. The beta of the same muscle types was also estimated from titration of muscle homogenates between pH 6.0 and 8.0. The contribution of Pi to total beta of the homogenates was subtracted to ascertain the non-Pi beta for each muscle. The non-Pi beta values were added to the actual amount of Pi present in the stimulated muscles to calculate a predicted beta at pH 7. The apparent beta calculated from PCr and pH changes in intact muscles and the predicted beta from homogenate titrations were in good agreement (38 +/- 9 vs. 38 slykes in cat biceps, 21 +/- 7 vs. 30 in cat soleus, and 30 +/- 6 vs. 27 in rat gastrocnemius). The results indicate that changes in pH during the first few seconds of contraction can be entirely accounted for by proton consumption via net PCr hydrolysis. PMID- 2246185 TI - Viscoplasticity of respiratory tissues. AB - Low-frequency mechanical behavior of various respiratory tissues shows certain similarities. In this study we test the hypothesis that rate-independent plastic processes along with rate-dependent viscoelastic processes are responsible. We considered oscillatory responses of several respiratory tissues measured over prescribed ranges of frequency (up to 6 Hz) and amplitude of forcing. These included the excised cat lung, the human chest wall in vivo, and two components of the chest wall: the excised dog rib cage and the excised rabbit abdominal viscera; some data were previously reported and some are new. We analyzed these data using the viscoplastic model of Hildebrandt (J. Appl. Physiol. 28: 365-372, 1970). It consists of three compartments: a plastoelastic compartment mechanically in parallel with a viscoelastic compartment, both in series with a lumped inertia. We fitted oscillatory data of the above respiratory tissues to the model by a least-squares technique. The fit was qualitatively consistent with the observations and exhibited moderately good to very good quantitative correspondence. As an independent verification of this approach, we obtained the stress relaxation after a step-volume change. Based on the oscillatory response of cat lungs, the calculated stress relaxation function was found to be generally consistent with corresponding observations. This study indicates that both plasticity and viscoelasticity appear to be important determinants of mechanical behavior of respiratory tissues at low frequencies and that inertial effects are negligible. PMID- 2246186 TI - Glucose feedings and exercise in rats: glycogen use, hormone responses, and performance. AB - This study compared the effects of glucose feeding and water on endurance performance, glycogen utilization, and endocrine responses to exhaustive running in rats. Forty-eight trained rats ran at approximately 70% peak O2 consumption (VO2) while receiving, via gavage, 1 ml of an 18% glucose solution or water every 30 min. Glucose- (GF) and water-fed rats (WF) were pair matched and killed at rest, at 25 or 50% of their previously determined run time to exhaustion, or at exhaustion. Run times to exhaustion were 4.6 +/- 1.0 and 3.0 +/- 0.9 h in GF and WF rats, respectively. In WF rats, plasma glucose declined continuously from a resting value of 7.4 +/- 0.5 to 1.8 +/- 0.5 mM at exhaustion and was lower than in GF rats at all exercise time points. In GF rats, glucose was maintained at 7.4 +/- 0.5 mM for 3 h before dropping to 3.9 +/- 0.6 mM at exhaustion. In both groups, liver and muscle glycogen decreased dramatically during the 1st h and changed only slightly thereafter. During the 3rd h, glycogen levels were maintained in GF rats but continued to decrease in WF rats (P less than 0.05). Insulin decreased during exercise and was not significantly different between groups. Glucagon, epinephrine, norepinephrine, and corticosterone increased to a greater extent in WF than in GF rats during the first 3 h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246187 TI - A theoretical study of the effect of airway smooth muscle orientation on bronchoconstriction. AB - If airway smooth muscle shortened in vivo to the extent that it does in vitro, then maximal bronchoconstriction would result in complete closure of virtually all airways. The fact that this does not happen indicates the existence of inhibitory mechanisms preventing maximal muscle shortening. There are many factors potentially limiting shortening in vivo. In this study we investigated one of these factors, the orientation of the smooth muscle around the airway wall. The airway was modeled as a cylinder of given wall thickness around which the muscle was wound as a spiral. The longitudinal and circumferential elasticities of the airway were embodied in a 2 x 2 matrix of elastic coefficients. We investigated smooth muscle shortening under three conditions: 1) a longitudinally stiff airway, 2) a circumferentially stiff airway, and 3) a longitudinally and circumferentially compressible airway. In case 1, for a given degree of smooth muscle shortening, airway resistance increased markedly with increasing pitch of the smooth muscle spiral. On the other hand, the muscle tension required to elicit a given change in resistance also increased markedly with pitch. In case 2, the effect with increasing pitch was reversed. In case 3, resistance first increased and then decreased as spiral pitch increased. Similarly, the muscle tension required to elicit a given change in resistance first increased and then decreased with pitch. These results suggest that the orientation of the smooth muscle about the airway may be very important in determining airway responsiveness. PMID- 2246188 TI - Oral versus axillary temperatures in human volunteers. AB - We measured the oral and axillary temperatures of 100 individuals (including 40 females) in the medical wards. Twenty six had fever ranging from 37.3 degrees C to 40.5 degrees C while the rest had normal temperature. Although the oral temperature was higher than axillary temperature in all the cases, there was no correlation between the two; in one case the difference was as high as 1 degrees C. We conclude that while recording temperature the site must be clearly stated, and no attempt must be made to extrapolate the axillary to the oral temperature. PMID- 2246189 TI - Immunoglobulins and allergy mediators in bronchial asthma. AB - Seventy four young asthmatics were evaluated to establish the role of immunoglobulins and allergy mediators in clinical asthma. They were categorized into Group I (n = 38) or Group II (n = 36) when having mild or severe bronchospasm respectively. In some patients, reversibility of bronchospasm (n = 35), exercise challenge (n = 24) and intradermal allergy testing (n = 24) were also studied. Seventy subjects had raised IgE levels (greater than 100 KU/L) but these did not correlate with the severity of clinical or exercise induced asthma or with reversibility of bronchospasm. An IgE level greater than 1000 KU/L was associated with more number of positive skin tests. Group II subjects had a shorter blood recalcification time (p less than 0.01) and higher levels of IgG, histamine and serotonin (p less than 0.001). It appears that severe asthma is associated with activation of blood coagulation, and release of allergy mediators contributes to the evolution of bronchospasm. Total IgE predicts the utility of skin testing in asthma. PMID- 2246190 TI - Psychopathology of delayed resumption of sexual activity after myocardial infarction. AB - A total of 300 male cases of myocardial infarction were analyzed to evaluate the effect of myocardial infarction on sexual activity with particular stress on resumption of sexual activity and to determine the factors in cases of delayed resumption. Sexual activity decreased with age and correlated negatively to total sexual activity. 26 per cent cases developed one or other symptoms which occurred during all the phases of sexual activity but were more marked during resolution phase. Sexual activity returned to normal within six months only in 11.33 per cent cases and in the remaining cases resumption was delayed. In 27.8 per cent cases phobia of marked exertion involved in sex act, created by physicians in 12.7 per cent was the factor responsible for the delayed resumption. Quality of sexual activity decreased in 39 per cent cases and it was due to change in position from Male on top to male on bottom position in 31 per cent cases. Counselling for sexual rehabilitation has been discussed. PMID- 2246191 TI - Fiberoptic bronchoendoscopic examination in patients with haemoptysis and normal chest roentgenogram. AB - The role of flexible fiberoptic bronchoendoscopic (FOB) examination was evaluated in a retrospective analysis in 155 patients with unexplained haemoptysis and normal chest skiagrams. The procedure was helpful in reaching a specific diagnosis in 11 (7.1%) patients, 4 of whom revealed mycobacteria in bronchial secretions and 7 had neoplastic lesions. In another 68 (43.9%) cases only non specific findings like inflammation were found, but the site of abnormality could be localized. We recommend the use of FOB in the routine assessment of haemoptysis. PMID- 2246192 TI - Small volume plasma exchange in Guillain-Barre syndrome: experience in 25 patients. AB - The impact of small volume plasma exchange (PE) on the treatment of Guillain Barre syndrome (GBS) was studied by comparing 25 patients treated with PE since 1982 with 25 historic controls treated without PE prior to 1982. Small volume PE was done by removing 10-15 ml plasma/kg body weight daily till the progression of the disease was arrested or recovery started. The PE group started recovering earlier (median 3 days, compared to 17.5 days in controls, 2P = 0.01), attained better clinical grades at the end of the 1st and 3rd months (2P = 0.001), and took much shorter time to recover by one clinical grade (median 15 days, compared to 53 days in controls, 2P = 0.01). The median duration of ventilation among the surviving patients was shorter in the PE group (8 days compared to 24.5 days, 2P = 0.10) and total number of complications was less in the PE group (15 events compared to 22 in the controls, 2P = 0.05). Three months after the onset of neuropathy, 13/25 controls were still bed bound, whereas only 4/25 in the PE group remained in that grade (2P = 0.02). There was no significant difference in the mortality rate in two groups (2P = 0.09), but the difference was significant in the subgroup of patients who were ventilated (2P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246193 TI - Frequency of bone marrow involvement in non-haematological malignancies. AB - Five hundred and fifty two bone marrow (BM) specimens (497 aspirates, 55 biopsies) from 518 patients with nonhaematological malignancies were examined to determine the frequency of metastatic deposits. BM involvement was highest in neuroblastoma (9/14), prostate cancer (2/4), retinoblastoma (3/7), Ewing's sarcoma (14/47), rhabdomyosarcoma (5/20) and small cell carcinoma of lung (3/18). BM aspiration smears were adequate in paediatric tumours (neuroblastoma, retinoblastoma, rhabdomyosarcoma) while BM biopsies were most useful in patients with Ewing's sarcoma, prostate cancer and small cell lung cancer. We conclude that BM is an easy investigation in the diagnosis and staging of nonhaematological cancers. PMID- 2246194 TI - Sickle haemoglobin, G-6PD deficiency and malaria in western Orissa. AB - Sixty cases of malaria were screened for sickle haemoglobin and G-6PD deficiency. Plasmodium vivax was detected in 40 (66%) and Plasmodium falciparum in 21 (35%) cases, with six of the latter having cerebral manifestation. Sickle Hb was found in 7 (11.5%) patients and G-6PD deficiency in 3 (5%) cases. Both patients with SS disease had vivax malaria, while of 5 with sickle cell trait 3 had only vivax, one only falciparum and one mixed infection. Amongst G-6PD deficient patients one had vivax and two falciparum malaria. One of the latter had both SC trait and G 6PD deficiency. Thus, adult persons with SS disease or SC trait were not found to be resistant to either vivax or falciparum malaria. A high frequency (5%) of G 6PD deficiency amongst malaria patients warrants a caution against indiscriminate use of 8-aminoquinoline drugs. PMID- 2246195 TI - Immunoreactive insulin and insulin degrading enzymes in erythrocytes. A preliminary report. AB - Immunoreactive insulin (IRI) and insulin degrading enzyme activity (IDEA) of the plasma and the corresponding erythrocyte lysate were estimated in 21 normal volunteers, 18 non insulin dependent diabetic patients (NIDDM), and 16 insulin dependent diabetics (IDDM). The erythrocytes contained several-fold higher concentrations of IRI than in plasma, both in normal and diabetic subjects. The values in controls ranged from 80 to 458 uU/ml against a range of 5 to 25 uU/ml in the corresponding plasma samples. The IRI contents of the diabetic patients were also similar. It showed no correlation to the fasting plasma glucose or the plasma IRI. Following an oral glucose load, no change occurred in the IRI content of the erythrocytes, unlike the changes seen in plasma. The IRI content of the lysate increased with dilution of the sample. The IDEA was higher in diabetic patients compared to controls, especially so in the IDDM (P less than 0.01). It also showed more than one peak activity at different pH of the reaction buffer, indicating the possibility of a complex of enzymes. Human erythrocytes contain large pools of IRI and its degrading enzymes. The significance of the pool of the insulin in non-target tissue needs to be studied. PMID- 2246196 TI - Changes in bronchoalveolar lavage and lung function in rheumatoid arthritis. A controlled study. AB - A comparative study of bronchoalveolar lavage was done in 30 patients with chronic rheumatoid arthritis and 30 age matched controls. Twelve patients had clinical lung disease (group I), 11 had lavage changes (group II) and 7 showed no abnormalities (group III). In group I, there was lower lung functions, tendency to older age and slightly longer history. There were no differences between the three groups (63% positive) in RA factor positivity. In the controls, lavage showed 67.3% return, 154.5 cells/cmm, 92.8% macrophages, 5.2% lymphocytes, 1.9% polymorphs and 0.2% eosinophils. In contrast, group I patients showed more polymorphs (10.3 +/- 8.3%) and group II more lymphocytes (14.5 +/- 18.7%; P less than 0.05). Thus, in chronic rheumatoid arthritic patients, bronchoalveolar lavage abnormalities may occur alone or in association with radiographic and functional abnormalities. PMID- 2246197 TI - Computed tomographic spectrum of neurocysticercosis. AB - Computed tomography (CT) is a very sensitive modality for the diagnosis of neurocysticercosis. Fifty eight patients were evaluated by plain radiography and CT scans. The initial presentation was as seizure disorder (33), raised intracranial tension (19), meningoencephalitis (5) and psychiatric manifestation (1). Histologically confirmed subcutaneous nodules were seen in 20 cases and ocular cyst in 2 cases. CT scan showed multiple calcification in 8 cases, disc lesions in 30,ring lesions in 3, and a combination of disc and ring lesions in another 13 cases. Low attenuation lesions were seen in 4 cases in combination with disc/disc and ring lesions. All 58 cases had supratentorial lesions while 19 cases had infratentorial lesions in addition. Perifocal or generalised oedema was seen in 33 and 11 cases respectively. The ventricles were compressed in one case, large in 2 cases and normal in the rest. CT scan is valuable in the diagnosis of neurocysticercosis. Its significance is different in the various clinical and radiological groups. PMID- 2246198 TI - Serum magnesium levels in chronic renal failure. Clinical significance and correlation with sodium potassium and calcium. AB - Fifty cases with chronic renal failure and 25 age and sex matched normal healthy controls were studied. The mean serum magnesium level was significantly higher (4.10 +/- 0.85 mg/dl) in the patients as compared to controls (2.40 +/- 0.14 mg/dl; p less than 0.001) and levels rose progressively with deterioration in renal function. Significantly higher serum magnesium levels were observed in patients of chronic renal failure with encephalopathy than in those without. Greater the impairment in level of consciousness, higher was the magnesium level. Improvement in neurological status correlated well with fall in serum magnesium level. The fall was significantly higher in patients on dialysis as compared to non-dialysed patients. Serum magnesium is a worthwhile tool in assessing duration of disease, morbidity and mortality in patients with chronic renal failure. Its estimation may help in evaluating conservative treatment and dialysis in chronic renal failure. PMID- 2246199 TI - Drug misuse--tip of the iceberg. PMID- 2246200 TI - Conn's syndrome. PMID- 2246202 TI - Horner's syndrome due to pulmonary hydatid disease. PMID- 2246201 TI - Stress thallium myocardial scintigraphy. Accurate marker of myocardial tissue perfusion. AB - Assessment of myocardial blood flow has been the subject of extensive research and study, ever since coronary artery disease has been recognised as a first rate killer of mankind. Non-invasive methods like routine ECG, exercise ECG, 2-D echocardiography lack sensitivity and specificity. The specificity of exercise ECG becomes less in patients with ventricular hypertrophy, intraventricular conduction delay, left bundle branch block (LBBB), previous myocardial infarction, subendocardial infarction, non specific ST-T changes at rest and exercise, and electrolyte imbalance; those taking various drugs such as digitalis and quinidine; and in evaluation of post bypass graft or post PTCA (percutaneous transluminal coronary angioplasty) status. Coronary angiography, which is an invasive procedure, provides direct proof of the presence and extent of coronary artery disease in the form of anatomical changes like luminal narrowing. It fails to give any information regarding small vessel disease or bridging of vessels in the cardiac musculature and in those with normal coronaries with anginal pain at stress. It also fails to provide direct information regarding myocardial tissue perfusion, which ultimately decides the outcome of the disease. In addition, coronary angiography involves some percentage of risk to the patient. It is in this context that thallium 201 myocardial scintigraphy occupies a unique position. It has none of the disadvantages of exercise ECG and it directly reflects myocardial perfusion at the tissue level. Stress thallium 201 scintigraphy directly quantitates the amount of myocardium involved as a result of previous myocardial infarction or ischaemia, unlike stress ECG and other non invasive modalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246203 TI - Keloids and diabetes in a family. AB - An interesting familial association of keloids with diabetes mellitus in three successive generations is reported. Keloids did not develop if the injection site was changed to the anterior abdominal wall. PMID- 2246204 TI - Splenic abscess. AB - We report a splenic abscess in an elderly diabetic female. Awareness of the disease is emphasised. PMID- 2246205 TI - Pulmonary bullous disease in Marfan syndrome. AB - Two young adults with marfanoid features who had pulmonary bullous disease are presented. One a young soldier, presented with increasing dyspnoea and an enlarging large pulmonary bulla on the right side. The bulla was under tension and was operated on. The other case was a young housewife who also presented with dyspnoea, and was found to have a cardiac murmur and multiple ectopic beats on initial examination. X-Ray chest revealed bilateral pulmonary bullous emphysema. Both the subjects had many features which are accepted as forme fruste of the Marfan syndrome. PMID- 2246206 TI - Duodeno--jejunal vascular malformation. AB - Vascular malformations are rare but an important cause of obscure upper gastrointestinal bleeding. A patient with a large vascular malformation involving the duodenum and proximal jejunum, presenting with a severe bout of melaena, is described. The diagnosis was suspected on endoscopy and confirmed by angiography and surgery. PMID- 2246207 TI - Diltiazem in neurology. PMID- 2246208 TI - Primary purulent pericarditis following renal transplantation. PMID- 2246209 TI - Carotid sinus syncope. PMID- 2246210 TI - Technical infarction. PMID- 2246211 TI - Laurence-Moon-Biedl syndrome--with unusual eye manifestations. PMID- 2246212 TI - Immunoglobulin status in epilepsy. PMID- 2246213 TI - Management of acute ischaemic VSD--so little time in which to do so much. PMID- 2246214 TI - Gugulipid: pro-lipaemic effect. PMID- 2246215 TI - Serum magnesium in acute myocardial infarct. PMID- 2246216 TI - Non-surgical treatment of acute upper gastrointestinal haemorrhage. PMID- 2246217 TI - Complete heart block after topical timolol. PMID- 2246218 TI - Bone marrow biopsy in the staging of malignant lymphoma. PMID- 2246219 TI - Hypokalaemia--Guillian Barre syndrome--a further experience. PMID- 2246220 TI - Irritable bowel syndrome: clinical presentations, enema users and dosage schedules of Ispaghula. PMID- 2246221 TI - Ranitidine in duodenal ulcer: phenomena of "primary failure" and "secondary failure". PMID- 2246222 TI - U wave and coronary artery disease. PMID- 2246223 TI - Spontaneous remission of insulin dependent diabetes mellitus. PMID- 2246224 TI - Diet, diabetes and atherosclerosis. PMID- 2246225 TI - The creative process in biomedical visualization: strategies and management. AB - The phases of the creative process (identification, preparation, incubation, insight, and elaboration/verification) are related to strategies for management of biomedical illustration projects. The idea that creativity is a mystery--and is unpredictable and uncontrollable--is not accepted. This article presents a practical way to encourage creative thinking in the biomedical visualization studio. PMID- 2246226 TI - Developing hospital identity manuals: a reference tool for illustrators. AB - Because of an increase in hospital marketing efforts, medical illustrators may be asked to assist in developing and implementing hospital identity manuals, which specify the graphic standards for visual communications media. A checklist survey of existing identity manuals and a literature review were conducted by one of the authors, a medical illustrator, to help her to develop a manual for her hospital employer. This article documents the literature review, the study, and the identity manual development, and presents recommendations to help other medical illustrators who might become involved in similar assignments. PMID- 2246227 TI - A clinical simulations laboratory ten years later. AB - Ten years ago a significant investment was made in simulations technology for medical education. A simulations complex was developed at St. Louis University School of Medicine consisting of a Group Activity/Observation Area, Skills Area, and simulated Physicians Offices Suite complete with observation and videotaping facilities. Since its inception, medical school faculty and other health science educators have utilized this area in ever-expanding and innovative ways. This is a success story about medical educators taking risks, implementing new ideas, and realizing those ideas. PMID- 2246228 TI - Administering a microcomputer-based problem-solving examination. AB - Administering a microcomputer-based problem-solving examination in the basic sciences to medical students poses a series of practical concerns not associated with traditional types of testing. This article reviews the issues of planning, student preparation, exam scheduling, student verification, and software security. Also discussed are the effects on student scores of exam scheduling and of students' familiarity with computers, student evaluations of the exam, and security and technical difficulties. PMID- 2246229 TI - Molecular cloning, sequencing, and expression of mouse ferrochelatase. AB - The cDNA encoding mouse ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) was isolated from a mouse erythroleukemia (MEL) cell cDNA library in lambda gt11 expression vector, by immunoscreening with a polyclonal antibody. Two full-length clones containing cDNA inserts of 2.2 and 2.90 kilobases were obtained. These clones have the same entire enzyme coding region, but alternative putative polyadenylation sites in the 3'-noncoding regions. From the deduced primary structure, a putative leader sequence of 53 amino acid residues resulted in a precursor protein of 420 amino acid residues (Mr 47,130) and a mature protein of 367 residues (Mr 41,692). The cDNA allows for the expression of active ferrochelatase by transfected culture cells. RNA blot analysis showed two species of ferrochelatase mRNA consistent with findings of two polyadenylation sites. Both the mRNAs increased by treatment of the MEL cells with dimethyl sulfoxide. The band pattern of the RNA of the mouse liver was the same as that of the MEL cells. Based on these results, we deduce that ferrochelatase in erythroid and hepatic cells can be only of one type. PMID- 2246230 TI - Nucleotide sequence and 40 S subunit assembly of Xenopus laevis ribosomal protein S22. AB - We have isolated and determined the nucleotide sequence of a cDNA encoding Xenopus laevis ribosomal protein S22. A synthetic S22 mRNA derived from this cDNA directs the synthesis of an in vitro translation product that is indistinguishable from S22 purified from Xenopus ovarian ribosomes. In vitro translated S22 is assembled into 40 S subunits when microinjected into the cytoplasm of oocytes. Analysis of the derived amino acid sequence indicates that Xenopus S22 is homologous to Escherichia coli ribosomal protein S10. PMID- 2246231 TI - Rate of electron transfer between cytochrome b561 and extravesicular ascorbic acid. AB - Cytochrome b561 transfers electrons across secretory vesicle membranes in order to regenerate intravesicular ascorbic acid. To show that cytosolic ascorbic acid is kinetically competent to function as the external electron donor for this process, electron transfer rates between cytochrome b561 in adrenal medullary chromaffin vesicle membranes and external ascorbate/semidehydroascorbate were measured. The reduction of cytochrome b561 by external ascorbate may be measured by a stopped-flow method. The rate constant is 450 (+/- 190) M-1 s-1 at pH 7.0 and increases slightly with pH. The rate of oxidation of cytochrome b561 by external semidehydroascorbate may be deduced from rates of steady-state electron flow. The rate constant is 1.2 (+/- 0.5) x 10(6) M-1 s-1 at pH 7.0 and decreases strongly with pH. The ratio of the rate constants is consistent with the relative midpoint reduction potentials of cytochrome b561 and ascorbate/semidehydroascorbate. These results suggest that cytosolic ascorbate will reduce cytochrome b561 rapidly enough to keep the cytochrome in a mostly reduced state and maintain the necessary electron flux into vesicles. This supports the concept that cytochrome b561 shuttles electrons from cytosolic ascorbate to intravesicular semidehydroascorbate, thereby ensuring a constant source of reducing equivalents for intravesicular monooxygenases. PMID- 2246232 TI - Renal metabolism and urinary excretion of platelet-activating factor in the rat. AB - The origin of platelet-activating factor (PAF) in the urine remains ill defined. The present study documents that [3H]PAF (3.5 mu Ci) injected into the renal artery of isolated control rat kidney preparations perfused at constant pressure with a cell-free medium containing 1% bovine serum albumin (BSA) was excreted in negligible amounts (0.034%) in the urine, whereas 6% was retained by the kidney. When kidneys were perfused with a BSA-free medium, 0.029 and 71% of the total radioactivity added to the perfusate was recovered in the urine and in the renal tissue, respectively. [3H]PAF urine excretion in proteinuric kidneys from adriamycin-treated rats was still negligible (0.015%). Analysis of the renal tissue-retained radioactivity in control and proteinuric kidneys perfused with 1% BSA indicated metabolism into long chain acyl-sn-glycero-3-phosphorylcholine species, lyso-PAF, glycerols, and intact PAF. Thin layer chromatography analysis of [3H]glycerol fraction in these renal extracts showed two major components comigrating with 1-O-alkylglycerol and 1-O-alkyl-2-fatty acylglycerol. Isolated proximal tubules, but not glomeruli from nephrotic rats exposed to increasing concentrations of BSA (0-4%), had a higher PAF uptake than control tubules for BSA concentrations ranging from 0 to 0.1%. Our findings in the isolated perfused kidneys indicate that, in normal conditions, circulating PAF is excreted in the urine in negligible amounts and that the altered glomerular permeability to proteins does not affect this excretion rate. Moreover, analysis of renal tissue radioactivity documented that the renal metabolism of PAF is comparable in control and nephrotic kidneys. PMID- 2246233 TI - Transcriptional control of the rat alpha 1-acid glycoprotein gene. AB - Dexamethasone strongly stimulates the production of alpha 1-acid glycoprotein (AGP) in rat liver. The regulated expression of AGP in cultured liver cells has been variably ascribed to the activation of AGP gene transcription, to change in the nuclear processing of AGP gene transcripts, or to both. Treatment of HTC cells with dexamethasone proportionally enhanced the rate of AGP gene transcription and the concentration of AGP mRNA. To assess whether hormone treatment is indeed capable of affecting posttranscriptionally the level of rat AGP mRNA, a hormone-independent expression vector containing the rat AGP gene was transiently introduced into HepG2 cells. None of the hormone combinations known to modulate expression of the endogenous AGP influenced the steady-state concentration of mature mRNA that was derived from the transgene. Hence, the existence of a hormone-sensitive posttranscriptional regulatory pathway for rat AGP gene expression could not be substantiated. PMID- 2246234 TI - A hybrid Azotobacter vinelandii-Clostridium pasteurianum nitrogenase iron protein that has in vivo and in vitro catalytic activity. AB - Site-directed mutagenesis and gene replacement procedures were used to construct a mutant strain of Azotobacter vinelandii which expresses a hybrid nitrogenase Fe protein. This hybrid Fe protein has its carboxyl-terminal 18 residues replaced with the 5 analogous residues from the Clostridium pasteurianum Fe protein sequence. The hybrid Fe protein is 13 amino acids smaller than the wild-type A. vinelandii Fe protein and has a net loss of 4 negatively charged residues, resulting in a change in size and charge. The strain which produces the hybrid Fe protein remained capable of diazotrophic growth, albeit at a reduced rate. Also, the purified hybrid Fe protein exhibited a maximum activity about one-half that of native Fe protein. These results demonstrate that the tight, inactive complex which is formed when A. vinelandii MoFe protein and C. pasteurianum Fe protein are mixed in heterologous reconstitution experiments cannot be accounted for only by differences in the A. vinelandii and C. pasteurianum Fe protein primary sequences located at their respective carboxyl termini. PMID- 2246235 TI - Arthropod hemocyanins. Molecular cloning and sequencing of cDNAs encoding the tarantula hemocyanin subunits a and e. AB - cDNA clones comprising the entire coding region of two out of the seven heterogeneous subunits of hemocyanin from the tarantula, Eurypelma californicum, were isolated from four cDNA libraries constructed from total RNA from the heart tissue of single spiders. Hybridization was first carried out using a tarantula hemocyanin subunit e partial cDNA, and several positive clones were isolated, including one containing a 2.2-kilobase full-length cDNA (lambda M1). The cDNA comprises an open reading frame for 623 amino acids, 34 nucleotides of the 5'noncoding region, and 286 nucleotides of the 3'-noncoding region. To select for other hemocyanin subunits, two 17-mer oligonucleotide mixtures, corresponding to the conserved regions in the copper A and copper B oxygen-binding site of chelicerate hemocyanins, were used as probes. Among the positive clones obtained, full-length cDNAs coding for subunit a were identified. The cDNA sequence determined from clone lambda K1 provides an open reading frame coding for 630 amino acids and includes the 5'- and 3'-noncoding regions. Northern blot analysis revealed single transcripts for subunits a and e, each 2.3 kilobases long. The cDNAs for subunits a and e were both found to lack any leader peptide sequence. This supports the idea that the mature protein accumulates in the cytoplasm and is released by cell rupture. PMID- 2246236 TI - Characterization of the receptors for vascular endothelial growth factor. AB - Vascular endothelial growth factor (vEGF) is a recently discovered mitogen for endothelial cells. It is also a potent angiogenic factor. We have characterized the vEGF receptors of endothelial cells using both binding and cross-linking techniques. Scatchard analysis of equilibrium binding experiments revealed two types of high-affinity binding sites on the cell surfaces of bovine endothelial cells. One of the sites has a dissociation constant of 10(-12) M and is present at a density of 3 x 10(3) receptors/cell. The other has a dissociation constant of 10(-11) M, with 4 x 10(4) receptors/cell. A high molecular weight complex containing 125I-vEGF is formed when 125I-vEGF is cross-linked to bovine endothelial cells. This complex has an apparent molecular mass of 225 kDa. Two other faintly labeled complexes with apparent molecular masses of 170 and 195 kDa also are detected. Reduction in the presence of dithiothreitol causes a substantial increase in the labeling intensity of the 170- and 195-kDa complexes, suggesting that these complexes are derived from the 225-kDa complex by reduction of disulfide bonds. The labeling of the vEGF receptors was inhibited by an excess of unlabeled vEGF but not by high concentrations of several other growth factors. Suramin and protamine, as well as several species of lectins, inhibited the binding. The expression of functional vEGF receptors was inhibited when the cells were preincubated with tunicamycin, indicating that glycosylation of the receptor is important for the expression of functional vEGF receptors. Pretreatment with swainsonine on the other hand, did not prevent formation of functional receptors. However, the mass of the 225-kDa complex is decreased by 20 kDa when 125I-vEGF is cross-linked to swainsonine-treated endothelial cells. PMID- 2246237 TI - Increased rate of phosphorylation-dephosphorylation of the translational initiation factor eIF-4E correlates with the induction of protein and glycoprotein biosynthesis in activated B lymphocytes. AB - A 10-50-fold, biphasic increase in the rate of 32Pi labeling of eIF-4E was closely correlated with the induction of protein and glycoprotein biosynthesis when resting murine splenic B lymphocytes (B cells) were activated by bacterial lipopolysaccharide or the combination of phorbol 12-myristate 13-acetate and ionomycin. The fraction of eIF-4E which was phosphorylated only increased from 46% in resting cells to 83% in lipopolysaccharide-activated cells. This discrepancy between the increase in the fraction of phosphorylated eIF-4E and the increase in 32Pi labeling suggested that the phosphoryl group of eIF-4E turns over slowly in resting B cells compared with activated cells. The turnover rate for the eIF-4E phosphate moiety in lipopolysaccharide-activated cells was rapid (t1/2 = 2 h) in comparison to the eIF-4E polypeptide chain, which did not turn over detectably in 6 h. Neither protein kinase C nor a cyclic nucleotide dependent protein kinase appeared to be involved in eIF-4E phosphorylation in B cells, based on the observations that the metabolic labeling of eIF-4E by 32Pi was insensitive to the protein kinase inhibitors H-7 and HA1004, and that maximal labeling occurred after protein kinase C activity was "down-regulated" to very low levels in phorbol 12-myristate 13-acetate/ionomycin-activated cells. Dephosphorylation in vivo was blocked by okadaic acid (IC50 = 200 nM). These results indicate that a rapid phosphorylation-dephosphorylation of eIF-4E is associated with high translation rates during the activation of B cells, and implicate protein phosphatase-1 (or possibly-2A) in the dephosphorylation of the initiation factor. PMID- 2246238 TI - Studies on the 4-carbon precursor in the biosynthesis of riboflavin. Purification and properties of L-3,4-dihydroxy-2-butanone-4-phosphate synthase. AB - The formation of the riboflavin precursor, 6,7-dimethyl-8-ribityllumazine, from 5 amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione requires a phosphorylated 4 carbon intermediate which has been designated as Compound X (Neuberger, G., and Bacher, A. (1985) Biochem. Biophys. Res. Commun. 127, 175-181). The enzyme catalyzing the formation of Compound X has been purified about 600-fold from the cell extract of the flavinogenic yeast Candida guilliermondii by chromatographic procedures. The purified protein appeared homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and consisted of a single polypeptide of 24 kDa. The committed substrate of the enzyme was identified as D-ribulose 5 phosphate. The enzyme yields two products which were identified as L-3,4 dihydroxy-2-butanone 4-phosphate and formate by NMR and CD spectroscopy. Mg2+ is required for activity. PMID- 2246239 TI - Interactions among mitochondrial aspartate aminotransferase, malate dehydrogenase, and the inner mitochondrial membrane from heart, hepatoma, and liver. AB - The inner mitochondrial membranes from bovine heart, rat liver, and Morris hepatoma 7777 all bound the mitochondrial isozymes of aspartate aminotransferase and malate dehydrogenase with comparable affinities and binding ratios (mg of enzyme bound per mg of membrane protein). A low molecular weight fraction separated from a detergent extract of the heart membrane by chromatography on Sephacryl S-300 contained most of the binding activity of the extract for the aminotransferase and had a dissociation constant for the aminotransferase of 0.2 microM. The protein component of the membrane binding sites for the aminotransferase was apparently present in this fraction because binding activity was largely eliminated by proteolysis with trypsin. When this fraction was chromatographed on an aminotransferase affinity column, only the portion that was bound and eluted by 0.25 M KCl associated with added aminotransferase. Unlike the membrane, which was markedly inhibited by the non-ionic detergent Genapol but was inhibited only 20% by trypsin, the binding activity of this subfraction was completely inhibited by trypsin but not by Genapol. This suggests, on the membrane, that the aminotransferase binds to the binding protein and is then transferred to lipids specifically associated with the binding protein. These putative lipids are presumably removed on the affinity column. Although the yield of the binding protein was low, there is probably ample binding protein in mitochondria to accommodate the aminotransferase. In every case, binding of the aminotransferase to the membrane inactivated the malate dehydrogenase binding site whereas malate dehydrogenase had little effect on the binding of the aminotransferase and only associated with the higher molecular weight fractions from the Sephacryl column that contained Complex I activity. Inactivation of the malate dehydrogenase site by the aminotransferase, but not vice versa, could result from aminotransferase associating with the binding protein and malate dehydrogenase with Complex I followed by association of the enzymes with lipids located in the same region of the membrane. However, since aminotransferase is more cationic, it is not displaced readily from the lipids by malate dehydrogenase. The relevance of these interactions to the organization of the enzymes is discussed. PMID- 2246240 TI - The nucleotide-binding site of HisP, a membrane protein of the histidine permease. Identification of amino acid residues photoaffinity labeled by 8-azido ATP. AB - The periplasmic histidine transport system (permease) of Escherichia coli and Salmonella typhimurium is composed of a soluble, histidine-binding receptor located in the periplasm and a complex of three membrane-bound proteins of which one, HisP, was shown previously to bind ATP. These permeases are energized by ATP. HisP is a member of a family of membrane transport proteins which is conserved in all periplasmic permeases and is presumed to be involved in coupling the energy of ATP to periplasmic transport. In this paper the nature of the ATP binding site of HisP has been explored by identification of some of the residues that come into contact with ATP. HisP was derivatized with 8-azido-ATP (N3ATP). Both the underivatized and the derivatized forms of HisP were solubilized, purified, and digested with trypsin. The resulting tryptic peptides were resolved by high pressure liquid chromatography, and peptides modified by N3ATP were isolated and sequenced. Two peptides, X and Z, spanning amino acid residues 16-23 and 31-45, were found to contain sites of N3ATP attachment at His19 and Ser41, respectively. Both peptides are close to the amino-terminal end of HisP; peptide Z is located in one of the well conserved regions comprising the nucleotide binding consensus motifs of the energy-coupling components of these permeases. These consensus motifs are found in many purine nucleotide-binding proteins. The relationship between the location of these residues and the overall structure of the ATP-binding site is discussed. PMID- 2246241 TI - Peptide and protein carboxyl-terminal labeling through carboxypeptidase Y catalyzed transpeptidation. AB - A survey of carboxypeptidase Y-catalyzed carboxyl-terminal modification of short peptides in the presence of various amino acids revealed that transpeptidation occurred in significant yield only with peptides containing a proline at the penultimate or antepenultimate position. For these peptides, transpeptidation was shown to occur specifically at the carboxyl side of the proline, thus suggesting a determining role of this residue for transpeptidation. Two model peptides, YPFP GPI and YPFVEPI, were studied in detail. Initial yields of transpeptidation in the presence of various nucleophiles were compared. Among natural amino acids, the highest yield was obtained with methionine, followed by other amino acids bearing hydrophobic side chains. In order to transpose the method of transpeptidation to a protein, a variant of Escherichia coli methionyl-tRNA synthetase bearing the carboxyl-terminal Glu-Pro-Met sequence was genetically created. Under the conditions optimized for the transpeptidation of YPF-VEPI with methionine, this protein could be labeled specifically at its carboxyl-terminal end. Moreover, the parameters of the labeling reaction were in agreement with those observed in the transpeptidation of the model peptide. PMID- 2246242 TI - Electron transfer from menaquinol to fumarate. Fumarate reductase anchor polypeptide mutants of Escherichia coli. AB - Fumarate reductase (FRD) of Escherichia coli is a four-subunit membrane-bound complex that is synthesized during anaerobic growth when fumarate is available as a terminal oxidant. The two subunits that comprise the catalytic domain, FrdA and FrdB, are anchored to the cytoplasmic membrane surface by two small hydrophobic polypeptides, FrdC and FrdD, which are also required for the enzyme to interact with quinone. To better define the individual roles of the FrdC and FrdD polypeptides in FRD complex formation and quinone binding, we selectively mutagenized the frdCD genes. Frd- strains were identified by their inability to grow on restrictive media, and the resulting mutant FRD complexes were isolated and biochemically characterized. The majority of the frdC and frdD mutations were identified as single base deletions that caused premature termination in either FrdC or FrdD and resulted in the loss of one or more of the predicted transmembrane helices. Two additional frdC mutants were characterized that contained single base changes resulting in single amino acid substitutions. All mutant enzyme complexes were incapable of oxidizing the physiological electron donor, menaquinol-6, in the presence of fumarate. Additionally, the ability of the mutant complexes to oxidize reduced benzyl viologen or reduce the ubiquinone analogue 2,3-dimethoxy-5-methyl-6-pentyl-1,4-benzoquinone and phenazine methosulfate with succinate as electron donor were also affected but to varying degrees. The separation of oxidative and reductive activities with quinones suggests there are two quinone binding sites in the fumarate reductase complex and that electron transfer occurs in two le- steps carried out at these separate sites. PMID- 2246243 TI - The absence of a m7G cap on beta-globin mRNA and alfalfa mosaic virus RNA 4 increases the amounts of initiation factor 4F required for translation. AB - beta-Globin mRNA and alfalfa mosaic virus (AMV) RNA 4, two naturally capped mRNAs, and satellite tobacco necrosis virus (STNV) RNA, a naturally uncapped mRNA, were prepared by in vitro transcription with and without a 5' m7G cap structure (m7G(5')ppp(5')N). The translation of the capped and uncapped forms of these mRNAs was measured in a crude S30 system and a partially purified system from wheat germ. In the S30 system the uncapped forms of beta-globin mRNA and AMV RNA 4 are much less active (greater than or equal to 10%) than their capped forms, whereas the uncapped and capped forms of STNV RNA are equally active. The low activity of uncapped beta-globin mRNA and AMV RNA 4 in the S30 system is due, in part, to inactivation of the uncapped mRNAs in this system. Additional studies, carried out in the partially purified system in which very little inactivation of the mRNAs occurs, show that the uncapped and capped forms of beta globin mRNA or AMV RNA 4 differ markedly with respect to the amount of eukaryotic initiation factor (eIF)-4F required for translation. For beta-globin mRNA the absence of the 5' cap structure increases the concentration of eIF-4F required for half-maximal translation about 6-fold (from 10 to 60 nM) and for AMV RNA 4 it increases the concentration of eIF-4F about 12-fold (from 5 to 60 nM). The concentrations of eIF-3, eIF-4A, and eIF-4B required for half-maximal translation of the uncapped forms of beta-globin mRNA and AMV RNA 4 are either the same or only slightly higher (1.5- to 2-fold) than the concentrations required for the capped forms. With STNV RNA the concentration of eIF-4F required for half-maximal translation of either uncapped or capped STNV RNA is 3 nM, and the concentrations of eIF-3, eIF-4A, and eIF-4B required for the two forms are also the same. The translation of the capped and uncapped forms of beta-globin mRNA and AMV RNA 4 is inhibited strongly by low concentrations of m7GTP in the partially purified system containing low concentrations of eIF-4F. Under the same conditions, the translation of capped or uncapped STNV RNA is inhibited only slightly by m7GTP. These findings suggest the possibility that the mechanism by which eIF-4F interacts and initiates translation with naturally uncapped mRNAs may not be identical to the mechanism by which eIF-4F interacts and initiates translation of naturally capped mRNAs. PMID- 2246244 TI - Kinetics and thermodynamics of oxygen, CO, and azide binding by the subcomponents of soybean leghemoglobin. AB - Leghemoglobin shows extreme high affinity behavior in the binding of both oxygen and CO. We have determined the temperature dependence of the rate constants for ligation of oxygen and CO and from these data the thermodynamics (delta G0, delta H0, delta S0) of ligation for the purified components of soybean leghemoglobin. X ray crystallography has shown that the heme cavity can easily accommodate ligands the size of nicotinate, and analysis of extended x-ray absorption fine structure data has shown that the Fe atom is in the mean plane of the heme in the leghemoglobin-CO complex. Ligation of oxygen and CO are in accord with this picture in that the Ea for oxygen binding is that expected for a diffusion controlled reaction and delta S0 for the ligation of both CO and oxygen is consistent with the simple immobilization of the ligand at the Fe, with no evidence for significant conformational changes in the protein or changes in solvation. At 20 degrees C the rate constants for oxygen and CO binding vary by 26-44% among the eight leghemoglobin components. For azide binding the variation is a factor of 2. These variations appear to arise from amino acid substitutions outside either the heme cavity or the two major paths for ligand entry to the heme. The distribution of leghemoglobin components varies with the age of the soybean nodule during the growing season. The changes in composition alone, however, would only allow the concentration of free oxygen to vary by about 3%. This finding calls into question models that ascribe a significant functional role to changes in the distribution of leghemoglobin components in regulating oxygen concentration in the nodule. PMID- 2246245 TI - Specificity and pH dependence for acylproline cleavage by prolidase. AB - Catalytic pH dependence for the hydrolytic activity of the enzyme prolidase with a series of dipeptide substrates is found to be generally bell-shaped (kcat/Km) or simple sigmoidal (kcat). An enzymic residue with a pKa value of 6.6 is found to be critically involved in the catalytic mechanism, as is the substrate amino group. Significant catalysis at a pH of 6.6 is also observed for prolidase with (alkylthio)acetylprolines and with haloacetylprolines. A reverse-protonation state mechanism for substrate binding and activation is postulated, involving a chelative interaction of the aminoacylamide portion of substrate with a strongly Lewis-acidic active site metal ion. PMID- 2246246 TI - Mechanism and inhibition of prolidase. AB - The pH dependence of Ki for inhibition of prolidase by acetylproline, proline, and trans-1,2-cyclopentanedicarboxylate follows a different pattern in each case, although deprotonation of an enzymic functional group with a pKa value of 6.6 perturbs ligand binding in every instance. Results are most easily explained with prolidase active as a metalloenzyme dimer exhibiting selective cooperative interactions. PMID- 2246247 TI - Structure of the lipophosphoglycan from Leishmania major. AB - The major cell surface glycoconjugate of the parasitic protozoan Leishmania major is a heterogeneous lipophosphoglycan. It has a tripartite structure, consisting of a phosphoglycan (Mr 5,000-40,000), a variably phosphorylated hexasaccharide glycan core, and a lysoalkylphosphatidylinositol (lysoalkyl-PI) lipid anchor. The structures of the phosphoglycan and the hexasaccharide core were determined by monosaccharide analysis, methylation analysis, fast atom bombardment-mass spectrometry, one- and two-dimensional 500-MHz (correlated spectroscopy (COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA] 1H NMR spectroscopy, and exoglycosidase digestions. The phosphoglycan consists of eight types of phosphorylated oligosaccharide repeats which have the general structure, [formula: see text] where R = H, Galp(beta 1-3), Galp(beta 1-3)Galp(beta 1-3), Arap(alpha 1-2)Galp(beta 1-3), Glcp(beta 1-3)Galp(beta 1-3), Galp(beta 1 3)Galp(beta 1-3)Galp(beta 1-3), Arap(alpha 1-2)Galp(beta 1-3)Galp(beta 1-3), or Arap(alpha 1-2)Galp(beta 1-3)Galp(beta 1-3)Galp(beta 1-3)Galp(beta 1-3), and where all the monosaccharides, including arabinose, are in the D-configuration. The average number of repeat units/molecule (n) is 27. Data are presented which suggest that the nonreducing terminus of the phosphoglycan is capped exclusively with the neutral disaccharide Manp(alpha 1-2)Manp alpha 1-. The structure of the glycan core was determined to be, [formula: see text] where approximately 60% of the mannose residues distal to the glucosamine are phosphorylated and where the inositol is part of the lysoalkyl-PI lipid moiety containing predominantly 24:0 and 26:0 alkyl chains. The unusual galactofuranose residue is in the beta configuration, correcting a previous report where this residue was identified as alpha Galf. Although most of the phosphorylated repeat units are attached to the terminal galactose 6-phosphate of the core to form a linear lipophosphoglycan (LPG) molecule, some of the mannose 6-phosphate residues may also be substituted to form a Y-shaped molecule. The L. major LPG is more complex than the previously characterized LPG from Leishmania donovani, although both LPGs have the same repeating backbone structure and glycolipid anchor. Finally we show that the LPG anchor is structurally related to the major glycolipid species of L. major, indicating that some of these glycolipids may have a function as precursors to LPG. PMID- 2246248 TI - Structure and chromosomal location of the human gene encoding cartilage matrix protein. AB - Cartilage matrix protein (CMP) is a major component of the extracellular matrix of nonarticular cartilage. The structure and chromosomal location of the human gene encoding CMP was determined by molecular cloning analysis. We used a partial chicken CMP cDNA probe to isolate three overlapping human genomic clones. From one of these clones, a probe containing 2 human CMP exons was isolated and used to map the gene to chromosome 1p35 and to screen a human retina cDNA library. Two overlapping cDNA clones were isolated. The predicted protein sequence of 496 amino acids includes a 22-residue signal peptide and a 474-residue mature protein of Mr 51,344. The human CMP gene and polypeptide are strikingly similar to the chicken CMP gene and polypeptide. Human CMP is 79% identical to chicken CMP and contains two homologous domains separated by an epidermal growth factor-like domain. One potential N-glycosylation site is conserved between the two species. The human CMP gene spans 12 kilobase pairs with 8 exons and 7 introns which are similar in size to those of the chicken CMP gene. Both RNA splice junctions of intron G in the human and chicken CMP genes are nonconforming to the consensus splice sequences. This suggests that the CMP gene utilizes a new RNA splicing mechanism. PMID- 2246249 TI - Binding of pancreatic carboxylester lipase to mixed lipid films. Implications for surface organization. AB - The hydrolysis of ester substrates in mixed monolayers with 1-palmitoyl-2 oleoylphosphatidylcholine by pancreatic carboxylester lipase (CEL) shows an abrupt increase from less than 10 to 100% when substrate abundance exceeds a critical value (Tsujita, T., Muderhwa, J.M., and Brockman, H.L. (1989) J. Biol. Chem. 264, 8612-8618). Adsorption of native CEL to these mixed lipid films under the same conditions shows a monotonic increase with substrate abundance to a maximum of approximately 4 pmol/cm2. In the range of low substrate hydrolysis, bound enzyme reaches 0.6 pmol/cm2 or about one-sixth of an enzyme monolayer. Given the high turnover number of the enzyme, absence of bound catalyst cannot explain the lack of substrate hydrolysis. Similarities of the adsorption data obtained with different substrates suggest a common, area-based mechanism with an excluded area for the phospholipid. Quantitative analysis confirms this and gives an excluded area of 43.5 +/- 1.0 A2/molecule. Comparable studies with the hydrolysis product, oleic acid, replacing each substrate show markedly different results. Up to oleic acid mol fractions of 0.5, bound CEL levels are essentially constant at 0.215 pmol/cm2. This behavior relative to substrate-containing films cannot be ascribed to differences in surface pressure, surface potential, monolayer compressibility, nonexcluded area, CEL denaturation, or oleic acid charge. Together with the ultrasensitive composition dependence of substrate hydrolysis, the data suggest that phospholipid-based organization of the surface is a primary regulator of enzyme binding and catalysis. PMID- 2246250 TI - Immunochemical evidence for the binding of caldesmon to the NH2-terminal segment of actin. AB - The binding of caldesmon and its actin-binding fragments to actin was studied by using peptide antibodies directed against two actin sites implicated in actomyosin interactions. Antibodies against residues 1-7 on skeletal alpha-actin strongly inhibited the binding of caldesmon to actin and perturbed to a smaller extent the interaction between actin and the actin binding fragments. Carbodiimide coupling of ethylenediamine to the NH2-terminal acidic residues on actin inhibited the binding of caldesmon and its fragments to actin to a similar extent as the (residues 1-7) antibodies. Antibodies against residues 18-28 showed only limited competition with caldesmon for the binding to actin. These results lead to the following conclusions. (i) The NH2-terminal residues on actin play an important role in the binding of caldesmon to actin, (ii) residues 18-28 on actin do not form a major caldesmon interaction site, and (iii) the actin-binding fragments do not contain the full actin-binding interface. These conclusions and other literature data suggest that caldesmon regulates the actomyosin ATPase by competing with myosin.ATP for the NH2-terminal segment on actin. PMID- 2246252 TI - Sialyl-alpha 2-6-mannosyl-beta 1-4-N-acetylglucosamine, a novel compound occurring in urine of patients with beta-mannosidosis. AB - Human beta-mannosidosis urine was fractionated by gel permeation chromatography on Bio-Gel P-2 and by high performance liquid chromatography on Partisil 10 SAX. Besides the disaccharide Man beta 1-4GlcNAc as the major component, a sialic acid containing compound was detected in an amount of 10% compared to that of Man beta 1-4GlcNAc. Structural characterization of the oligosaccharide and of its reduced analogue by sugar composition analysis, methylation analysis, gas-liquid chromatography-mass spectrometry, and 500-MHz 1H NMR spectroscopy gave conclusive evidence for a novel urinary constituent: NeuAc alpha 2-6Man beta 1-4GlcNAc. This linear trisaccharide can be considered as the result of an alpha 2-6-sialylation of the major accumulating compound, Man beta 1-4GlcNAc. The hitherto unknown linkage between sialic acid and mannose was shown to be susceptible to sialidase digestion. PMID- 2246251 TI - Characterization of caldesmon binding to myosin. AB - Caldesmon inhibits the binding of skeletal muscle subfragment-1 (S-1).ATP to actin but enhances the binding of smooth muscle heavy meromyosin (HMM).ATP to actin. This effect results from the direct binding of caldesmon to myosin in the order of affinity: smooth muscle HMM greater than skeletal muscle HMM greater than smooth muscle S-1 greater than skeletal muscle S-1 (Hemric, M. E., and Chalovich, J. M. (1988) J. Biol. Chem. 263, 1878-1885). We now show that the difference between skeletal muscle HMM and S-1 is due to the presence of the S-2 region in HMM and is unrelated to light chain composition or to two-headed versus single-headed binding. Differences between the binding of smooth and skeletal muscle myosin subfragments to actin do not result from the lack of light chain 2 in skeletal muscle S-1. In the presence of ATP, caldesmon binds to smooth muscle myosin filaments with a stoichiometry of 1:1 (K = 1 x 10(6) M-1). Similar results were obtained for the binding of caldesmon to smooth muscle rod as well as the binding of the purified myosin-binding fragment of caldesmon to smooth muscle myosin. The binding of caldesmon to intact myosin is ATP sensitive. The interaction of caldesmon with myosin is apparently specific and sensitive to the structure of both proteins. PMID- 2246253 TI - Identification and characterization of heparan sulfate-binding proteins from human lung carcinoma cells. AB - The heparan sulfate proteoglycan/heparin-binding proteins of the human lung carcinoma cell line LX-1 have been identified, partially purified, and characterized. Analysis of the binding of [3H]heparin to membranes isolated from LX-1 cells indicated the presence of two classes of binding sites, with Kd values of approximately 2 x 10(-10) and 4 x 10(-8) M and corresponding Bmax values of 1 x 10(5) and 2 x 10(7) binding sites/cell. Binding was also observed with isolated heparan sulfate chains and with intact heparan sulfate proteoglycan isolated from two different cell types. With each ligand, binding was inhibited by addition of unlabeled heparin. The binding proteins were extracted from LX-1 cell membranes in detergent solution, and two size classes of binding proteins were identified by overlaying transblots of electrophoretically separated proteins with radioactive ligands. These two classes of binding proteins were shown to contain doublets with estimated molecular masses of approximately 16 kDa (HSBP1A and HSBP1B) and approximately 32 kDa (HSBP2A and HSBP2B). The proteins were partially purified by heparin-Sepharose chromatography and shown to bind heparin and heparan sulfate proteoglycan. By amino acid composition, N-terminal amino acid sequence, and reactivity with antibody, HSBP1A was shown to be very similar to histone 2B; HSBP1B may also be related to histone 2A. HSBP2A and HSBP2B, however, did not react with antibodies to the major histones and had compositions different from one another and from HSBP1. PMID- 2246254 TI - Antennal-specific pheromone-degrading aldehyde oxidases from the moths Antheraea polyphemus and Bombyx mori. AB - Female moths produce blends of odorant chemicals, called pheromones. These precise chemical mixtures both attract males and elicit appropriate mating behaviors. To locate females, male moths must rapidly detect changes in environmental pheromone concentration. Therefore, the regulation of pheromone concentration within antennae, their chief organ of smell, is important. We describe antennal-specific aldehyde oxidases from the moths Antheraea polyphemus and Bombyx mori that are capable of catabolizing long chain, unsaturated aldehydes such as their aldehyde pheromones. These soluble enzymes are associated uniquely with male and female antennae and have molecular masses of 175 and 130 kDa, respectively. The A. polyphemus aldehyde oxidase has been localized to the olfactory sensilla which contain the pheromone receptor cell dendrites. These same sensilla contain a previously described sensilla-specific esterase that degrades the acetate ester component of A. polyphemus pheromone. We propose that sensillar pheromone-degrading enzymes modulate pheromone concentration in the receptor space and hence play a dynamic role in the pheromone-mediated reproductive behaviors of these animals. PMID- 2246255 TI - Analysis of a splice acceptor site mutation which produces multiple splicing abnormalities in the human argininosuccinate synthetase locus. AB - The cloned argininosuccinate synthetase gene from a citrullinemia patient's fibroblast cell line revealed a single base substitution (G to C) within the splice acceptor site of the last intron. The mutation abolished normal RNA splicing, and, by cDNA analysis, three abnormal splicing pathways were demonstrated. The major pathway involved the activation of a cryptic acceptor site in the last exon that resulted in a deletion of seven nucleotides in the mature RNA. Another pathway involved a downstream cryptic acceptor site, that is 388 nucleotides downstream from the first cryptic site. Northern blot analysis showed that this second cryptic site is present on the minor 2.7-kilobase mRNA, but not on the major species of argininosuccinate synthetase mRNA, which is 1.7 kilobases in length. Using this aberrant cDNA as a probe, the cDNA of the 2.7 kilobase mRNA was isolated and studied. Sequence analysis suggests that this species of RNA is the one that bypasses the polyadenylation signal employed by the 1.7-kilobase RNA. Since both transcripts encounter the same translation termination codon, both RNAs should encode identical protein. Furthermore, a tract of 22 repeats of d(CA).(GT) is found at the 3' end of the gene and this repeat sequence is present on the 2.7-kilobase RNA. The third pathway of the abnormal splicing revealed a rare class of transcript that has the last intron retained in the mature RNA. This study shows that in human the intron inclusion can occur through a naturally occurring point mutation. All these abnormally spliced RNAs resulted in a protein reading frame shift. PMID- 2246256 TI - Primary structure of the target of calcium vector protein of amphioxus. AB - CaVPT, a target protein of Ca2(+)-vector from amphioxus muscle, was purified from its complex with CaVP after dissociation by 6 M urea and chromatographies on DEAE cellulose and calmodulin-Sepharose. The amino acid sequence of CaVPT has been determined. The protein is composed of 243 residues and possesses an unblocked N terminus. Its molecular weight is 26,621, distinctly lower than the apparent molecular weight deduced from electrophoresis on sodium dodecyl sulfate containing gels. CaVPT contains a potential Asn-linked glycosylation site, four potential protein kinase C phosphorylation sites, and two casein kinase II phosphorylation sites. From the sequence the following three particular domains can be inferred: a collagen-like N-terminal segment, rich in Pro and Ala, that resembles the N-terminal segment of skeletal muscle myosin light chain kinase; next to it (from residues 33 to 50) is located a strongly amphiphilic and basic alpha-helical segment which likely binds the calcium vector protein since a proteolytic cut after Arg50, occurring occasionally during the purification of CaVPT, impairs the binding to immobilized calmodulin. This segment is followed by two immunoglobulin folds. The two immunoglobulin folds typically belong to the C2 subclass and particularly resemble those present in the neural cell surface adhesion molecules NCAM, L1, F11, MAG, TAG-1, fasciclin II, and amalgam. Recently, the presence of immunoglobulin folds of this type has been reported in some intracellular muscular proteins, namely in smooth muscle myosin light chain kinase, striated muscle C protein and titin, as well as in the nematode 600-kDa protein twitchin. From this structural study we can formulate the working hypothesis that CaVPT acts on the structure of the thick filament in muscle or regulates, perhaps via other immunoglobulin fold-containing proteins. PMID- 2246257 TI - Mitochondrial phosphate transport. N-ethylmaleimide insensitivity correlates with absence of beef heart-like Cys42 from the Saccharomyces cerevisiae phosphate transport protein. AB - The mitochondrial phosphate transport protein (PTP) has been purified in a reconstitutively active form from Saccharomyces cerevisiae and Candida parapsilosis. ADP/ATP carriers that copurify have been identified. The PTP from S. cerevisiae migrates as a single band (35 kDa) in sodium dodecyl sulfate gels with the same mobility as the N-ethylmaleimide-alkylated beef heart PTP. It does not cross-react with anti-sera against beef heart PTP. The CNBr peptide maps of the yeast and beef proteins are very different. The rate of unidirectional phosphate uptake into reconstituted proteoliposomes is stimulated about 2.5-fold to a Vmax of 170 mumol of phosphate min-1 (mg PTP)-1 (22 degrees C) by increasing the pHi of the proteoliposomes from 6.8 (same as pHe) to 8.0. The Km for Pi of this reconstituted activity is 2.2 mM. The transport is sensitive to mersalyl (50% inhibition at 60 microM) and insensitive to N-ethylmaleimide. We have purified peptides matching the highly conserved motif Pro-X-(Asp/glu)-X-X (Lys/Arg)-X-(Arg/lys) (X is an unspecified amino acid) of the triplicate gene structure sequence of the beef heart PTP. The N-ethylmaleimide-reactive Cys42 of the beef heart protein, located between the two basic amino acids of this motif (Lys41-Cys42-Arg43), is replaced with a Thr in the yeast protein. This substitution most likely is responsible for the lack of N-ethylmaleimide sensitivity of the yeast protein and mersalyl thus reacts with another cysteine to inhibit the transport. Finally it is concluded that Cys42 has no essential role in the catalysis of inorganic phosphate transport by the mitochondrial phosphate transport protein. PMID- 2246258 TI - Interaction between light harvesting chlorophyll-a/b protein (LHCII) kinase and cytochrome b6/f complex. In vitro control of kinase activity. AB - We have previously reported that the cytochrome b6/f complex may be involved in the redox activation of light harvesting chlorophyll-a/b protein complex of photosystem II (LHCII) kinase in higher plants (Gal, A., Shahak, Y., Schuster, G., and Ohad, I. (1987) FEBS Lett. 221, 205-210). The aim of this work was to establish whether a relation between the cytochrome b6/f and LHCII kinase activation can be demonstrated in vitro. Preparations enriched in cytochrome b6/f obtained from spinach thylakoids by detergent extraction and precipitation with ammonium sulfate followed by different procedures of purification, contained various amounts of LHCII kinase activity. Analysis of the cytochrome b6/f content and kinase activity of fractions obtained by histone-Sepharose and immunoaffinity columns, immunoprecipitation and sucrose density centrifugation, indicate functional association of kinase and cytochrome b6/f. Phosphorylation of LHCII by fractions containing both cytochrome b6/f and kinase was enhanced by addition of plastoquinol-1. LHCII phosphorylation and kinase activation could be obtained in fractions prepared by use of beta-D-octyl glucoside but not when 3 [(cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate was used as the solubilizing detergent. Kinase activity could be inhibited by halogenated quinone analogues (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone and 2,3-diiodo-5-t butyl-p-benzoquinone) known to inhibit cytochrome b6/f activity. However, kinase activity was inhibited by these analogues in all preparations including those which could not phosphorylate LHCII. We thus propose that the redox activation of LHCII phosphorylation is mediated by kinase interaction with cytochrome b6/f while the deactivation may be related to a distinct quinone binding site of the enzyme molecule. PMID- 2246259 TI - Vacuolar targeting and posttranslational processing of the precursor to the sweet potato tuberous root storage protein in heterologous plant cells. AB - Sporamin, the tuberous root storage protein of the sweet potato, which is localized in vacuoles, is synthesized as a prepro-precursor with an N-terminal sequence of amino acids that includes a signal peptide and an additional pro segment of 16 amino acids. A full-length cDNA for sporamin was placed downstream of the 35 S promoter of cauliflower mosaic virus and introduced into tobacco and sunflower genomes by Ti plasmid-mediated transformation. A polypeptide of nearly the same size as mature sporamin from the sweet potato was detected in transformed calli of tobacco and sunflower, as well as in the leaves, stems, and roots of regenerated, transgenic tobacco plants. Amino acid sequence analysis of the nearly mature-sized form of sporamin from the transformed tobacco cells revealed that it is actually longer by three amino acids at its N terminus than authentic sporamin purified from the sweet potato. By pulse labeling of suspension-cultured tobacco cells with [35S]methionine, the pro-form of the precursor to sporamin, but not the prepro-precursor, was detected. The 35S labeled proform was chased to the nearly mature-sized form via an intermediate form which is slightly larger than the nearly mature-sized form. Analysis by Edman degradation of the intermediate form that was labeled in vivo with [3H]histidine suggested that it is longer by two amino acids at its N terminus than the nearly mature-sized form of sporamin. These results suggest that at least two steps of posttranslational processing of the pro-form occurs sequentially in tobacco cells. The posttranslational processing of the pro-form of the precursor to sporamin was inhibited by monensin, suggesting that this step takes place in the acidic compartment, probably in the vacuole. All of the sporamin polypeptides synthesized in transformed tobacco cells were retained inside the cell and sporamin was localized in the vacuole, as judged from results of subcellular fractionation. These results indicate that sporamin is appropriately targeted to the vacuole in tobacco cells. PMID- 2246260 TI - Nerve growth factor rapidly induces expression of the 68-kDa neurofilament gene by posttranscriptional modification in PC12h-R cells. AB - We have isolated a subclonal cell line of PC12, PC12h-R, which is characterized by its rapid response to nerve growth factor (NGF) in extending its neurites. The mRNA levels of the 68-kDa neurofilament (NF-L) increased severalfold as early as 3 h after the addition of NGF, but this was not accompanied by an increase in the transcription rate. Analysis of the stabilities of 3.5- and 2.3-kilobase (kb) NF L mRNAs using actinomycin D revealed that 2.3-kb mRNA was degraded much faster than the 3.5-kb species and that NGF apparently stabilized NF-L mRNAs. These results show that the NF-L gene can be regulated posttranscriptionally, a finding that may be important in responding to the acute demand for neurofilament syntheses. PMID- 2246261 TI - Structure of the 68-kDa neurofilament gene and regulation of its expression. AB - The complete structure of the mouse 68-kDa neurofilament (NF-L) gene was elucidated. We cloned cDNAs corresponding to 3.5- and 2.3-kb NF-L mRNA, including their polyadenylation sites. Sequence analysis revealed that these NF-L mRNAs arose from the alternative use of two polyadenylation sites in exon 4. Promoter analysis using NF-L promoter-beta-galactosidase fusion plasmids determined regions responsible for its basic promoter activity, which were located between 328 and -36 base pairs from the transcription initiation site. These promoter fusion plasmids induced a significant level of beta-galactosidase in NF nonproducing C6 cells as well as in NF-producing PC12h cells. The in vitro transcription assay using HeLa cell extract also showed that this promoter exhibited strong transcriptional activity. Little difference in NF-L mRNA stability was observed between the two cells. However, nuclear run-off assay revealed that the NF-L gene was not transcribed in NF-nonproducing C6 cells. These data suggest that the strong promoter activity of the NF-L gene is repressed in vivo at the transcription initiation level in a tissue-specific manner. PMID- 2246262 TI - Human monocyte carboxylesterase. Purification and kinetics. AB - Human peripheral blood monocytes were isolated by density gradient centrifugation and purified by counterflow centrifugation elutriation. Membrane-localized carboxylesterase (CBE) was extracted with nonionic detergent (Triton X-100) and purified by ion exchange (DEAE-cellulose), gel filtration (Sephacryl S-300), hydroxylapatite column, and high performance liquid chromatography. The purified enzyme migrated on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single protein band with a molecular weight of 60,000. Under nondenaturing conditions, monocyte CBE formed a trimer and eluted from a gel filtration column as a protein with an approximate molecular weight of 200,000. Electrophoretic patterns of the enzyme on polyacrylamide gels run a neutral pH did not vary during enzyme purification. At least four major isoenzymes of human monocyte CBE were observed with isoelectric points between 7.5 and 7.8. Pure human monocyte CBE hydrolyzed short chain alpha-naphthyl, o-nitrophenyl, and p-nitrophenyl esters. Amide esters and thioesters were not hydrolyzed by the enzyme. Short chain alcohols activated the enzyme and organophosphorus compounds, diphenyl carbonate, sodium fluoride, and phenylmethylsulfonyl fluoride inhibited the enzyme. EDTA and sulfhydryl reagents had no effect on enzyme activity. The amino acid content of the enzyme was consistent with other CBEs. Inhibitors reacted either with the active or effector site of the enzyme. Purified enzyme now permits the characterization of CBE structure and regulation. PMID- 2246263 TI - Cloning and sequencing of a cDNA for the hemolymph juvenile hormone binding protein of larval Manduca sexta. AB - A cDNA for the hemolymph juvenile hormone binding protein (JHBP) of larval Manduca sexta has been cloned and sequenced. The JHBP was purified to homogeneity from fifth instar larval hemolymph using gel filtration chromatography, ion exchange chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Polyclonal rabbit antibodies, generated in response to this protein, were used to identify and isolate JHBP cDNAs from a fat body expression library in bacteriophage lambda ZAPII. Eleven putative JHBP cDNA clones were isolated and subcloned into Bluescript plasmid; cDNA inserts were approximately 750 base pairs in length. A 36-kDa immunoreactive protein was expressed from these plasmids; this beta-galactosidase fusion protein, like the authentic 32-kDa JHBP, was specifically photoaffinity labeled with [3H] epoxyhomofarnesyl diazoacetate (EHDA). Single-stranded DNA from one clone was sequenced by the Sanger dideoxynucleotide method, using deletion and custom primer techniques. A mature translation product was identified which had 226 amino acid residues, a molecular mass of 25,111 daltons, and a predicted isoelectric point (pI) of 5.40. The cDNA correctly predicts the N-terminal amino acid sequence and the amino acid composition of an authentic M. sexta hemolymph JHBP. A computer search of protein and nucleic acid data bases failed to reveal any related sequences. Thus, M. sexta hemolymph JHBP appears to be the first member of a new superfamily of insect hormone binding proteins. PMID- 2246264 TI - Identification and characterization of hepatocyte-specific regulatory regions of the rat pyruvate kinase L gene. The synergistic effect of multiple elements. AB - The rat pyruvate kinase L (PKL) gene produces the L- and R-type isozymes by alternative transcription that is regulated in a tissue-specific manner. To investigate which DNA elements are involved in hepatocyte-specific expression of the L-type isozyme, we performed transient DNA transfer experiments with PKL/chloramphenicol acetyltransferase fusion genes. We found three positive regulatory regions required for expression of the L-type isozyme in adult rat hepatocytes by functional analyses of a series of 5' and internal deletion constructs of the fusion genes. These regions, designated as PKL-I, PKL-II, and PKL-III, were located between nucleotides -76 and -94, -126 and -149, and -150 and -170, respectively. PKL-I showed enhancer-like activity alone, whereas PKL-II and PKL-III did not have any independent effect. Combinations of L-I + L-II and L II + L-III, but not of L-I + L-III, showed synergistic enhancer activities when oriented in the same direction. The inclusion of all three elements oriented in the same direction had the maximum synergistic effect, indicating that these elements function as a unit. This unit enhanced expression from heterologous as well as homologous promoters in a manner that was independent of its orientation and position relative to the cap site. The activity of the unit was not detected in HeLa cells or K562 erythroleukemia cells, suggesting that this unit possessed cell-type specificity. PKL-I consists of a palindrome sequence 5' CTGGTTATACTTTAACCAG-3', which contain a sequence homologous to the LF-B1-binding site. PKL-II contains the sequence 5'-TTCCTGGACTCTGGCCCCCAGTGT-3', which is similar to that of the LF-A1-binding site. PKL-III contains a palindrome sequence 5'-CCACGGGGCACTCCCGTGG-3', which include a sequence homologous to the binding site of the adenovirus major late transcription factor. Gel retardation assay indicated that the different trans-acting factors interacted with three elements and that the transacting protein bound to PKL-I was in fact LF-B1. However, the trans-acting factors bound to PKL-II and PKL-III were different from LF-A1 and major late transcription factor, respectively. Thus, we conclude that three cis acting elements are very important for specific expression of the PKL gene in hepatocytes and that LF-B1 and two unknown factors bound to these elements interact with each other to cause a synergistic effect. PMID- 2246265 TI - Purification and characterization of a methionine aminopeptidase from Saccharomyces cerevisiae. AB - Methionine aminopeptidase (MAP), which catalyzes the removal of NH2-terminal methionine from proteins, was isolated from Saccharomyces cerevisiae. The enzyme was purified 472-fold to apparent homogeneity. The Mr of the native enzyme was estimated to be 36,000 +/- 5,000 by gel filtration chromatography, and the Mr of the denatured protein was estimated to be 34,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 7.0, and its pI is 7.8 as determined by chromatofocusing on Mono P. The enzyme was inactivated by metalloprotease inhibitors (EDTA, o-phenanthroline and nitrilotriacetic acid), sulfhydryl-modifying reagents (HgCl2 and p hydroxymercuribenzoic acid), and Zn2+. Yeast MAP failed to cleave methionine p nitroanilide. Among 11 Xaa-Ala-Ser analogues (Xaa = Ala, Asp, Gln, Glu, Ile, Leu, Lys, Met, Phe, Pro, and Ser), MAP cleaved only Met-Ala-Ser. MAP also cleaved methionine from other tripeptides whose penultimate amino acid residue is relatively small and/or uncharged (e.g. Pro, Gly, Val, Thr, or Ser) but not when bulky and/or charged (Arg. His, Leu, Met, or Tyr). Yeast MAP displayed similar substrate specificities compared with those of Escherichia coli (Ben-Bassat, A., Bauer, K., Chang, S.Y., Myambo, K., Boosman, A., and Chang, S. (1987) J. Bacteriol. 169, 751-757) and Salmonella typhimurium MAP (Miller, C., Strauch, K. L., Kukral, A. M., Miller, J. L., Wingfield, P. T., Mazzei, G. J., Werlen, R. C., Garber, P., and Movva, N. R. (1987) Proc. Natl, Acad. Sci. U.S.A. 84, 2718-2722). In general, the in vitro specificity of yeast MAP is consistent with the specificity observed in previous in vivo studies in yeast (reviewed in Arfin, S. M., and Bradshaw, R. A. (1988) Biochemistry 27, 7979-7984). PMID- 2246266 TI - Purification and characterization of a novel intracellular acid proteinase from the plasmodia of a true slime mold, Physarum polycephalum. AB - An acid proteinase was purified to apparent homogeneity from the plasmodia of a slime mold, Physarum polycephalum, by a combination of detergent extraction, acid precipitation, and column chromatographies on DEAE-Sephadex, hydroxylapatite, CM Sephadex, and Sephadex G-100. The enzyme was shown to be composed of two polypeptide chains (a 31-kDa heavy chain and a 23-kDa light chain) cross-linked by disulfide bond(s). The NH2-terminal amino acid sequence of the heavy chain was determined to be Ala-Gly-Val- Asp-Gly-Tyr-Ile-Val-Pro-Tyr-Val-Ile-Phe-Asp-Leu-Tyr Gly-Ile-Pro-Tyr and that of the light chain to be Ala-Glu-Pro-Pro-Ile. The heavy chain contained carbohydrate moiety composed of mannose, glucosamine, fucose, and glucose. The enzyme was optimally active at pH 1.7 toward hemoglobin as a substrate. Among the proteinase inhibitors tested only diazoacetyl-D,L-norleucine methyl ester, a typical aspartic proteinase inhibitor, inhibited the acid proteinase in the presence of cupric ions. It was insensitive to the other typical aspartic proteinase inhibitors, pepstatin A and 1,2-epoxy-3-(p nitrophenoxy)propane. The enzyme hydrolyzed Lys-Pro-Ile-Glu-Phe(4-NO2)-Arg-Leu at the Phe-Phe(4-NO2) bond, but could not hydrolyze another synthetic pepsin substrate, N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine. The enzyme showed a unique substrate specificity toward oxidized insulin B chain. The major cleavage sites were the bonds Gly8-Ser9, Leu11-Val12, Cya19-Gly20, and Phe24-Phe25, and the Gly8-Ser9 bond was most susceptible. These results indicate that the enzyme is a novel type of intracellular acid proteinase with a unique substrate specificity. PMID- 2246267 TI - CDC6 mRNA fluctuates periodically in the yeast cell cycle. AB - Using cultures synchronized by two independent procedures, alpha-factor arrest and centrifugal elutriation, we have investigated the expression of the Saccharomyces cerevisiae CDC6 gene through the cell cycle. Our results show that the CDC6 gene is periodically expressed in the yeast cell cycle. The level of CDC6 transcripts increases in late G1, reaching a peak (approximately 10-20-fold over the initial level) at about the G1/S phase boundary. The peak of CDC6 mRNA was observed to overlap or slightly precede that of the CDC8 message, and to obviously precede that of the histone H2A message by some 25 min. Unlike histone H2A mRNA, the CDC6 mRNA as well as CDC8 mRNA were not affected by hydroxyurea treatment. These results suggest that regulation of H2A mRNA is different from that of CDC6 or CDC8. We have studied the 5'-flanking regions of CDC6 and other cell cycle-regulated genes. DNA sequence analysis of the CDC6 promoter revealed two sequences, 5'-C/GACGCGNC/G-3' and 5'-PuGNAGAAA-3' (where Pu is a purine, and N is any nucleotide), which are repeated three times each. Similar sequence elements have also been found among several cell cycle-regulated genes, including the CDC8 gene, but are not found upstream of histone genes. The possible significance of these elements is discussed. PMID- 2246268 TI - Phosphorylation of neutrophil 47-kDa cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. AB - Activation of the phagocytic cell superoxide-generating NADPH oxidase requires interaction of cytosolic and membrane-associated components. With most stimuli activation of the oxidase is accompanied by multisite phosphorylation of the 47 kDa cytosolic oxidase factor (p47) which translocates from cytosol to membranes. Native p47 is a highly basic protein that undergoes stepwise charge shifts with successive phosphorylation events. Phosphorylation of p47 was studied by immunoprecipitation from neutrophil cytosol and membrane fractions followed by two-dimensional gel electrophoresis and autoradiography. In the resting cell p47 was not phosphorylated. In the cytosol of phorbol myristate acetate-activated neutrophils eight distinct p47 phosphoproteins were present. The membrane fraction from these activated cells contained a family of p47 phosphoproteins of electrophoretic mobilities identical to those seen in cytosol plus an additional, more acidic p47 phosphoprotein not present in cytosol. Very early after activation (30 s) only the four most acidic p47 phosphoproteins were present in the membrane fraction. Only at later times (5-15 min) was the full spectrum of p47 phosphoproteins present in the membrane fraction. In contrast, the full spectrum of p47 phosphoproteins was present in the cytosol over the entire time course we studied. In neutrophils from patients with cytochrome b558-deficient chronic granulomatous disease p47 phosphorylation was incomplete and p47 translocation to membrane did not occur. These studies demonstrated that the cytochrome was essential for formation of the three most acidic p47 phosphoproteins and greatly augmented formation of the fourth most acidic p47 phosphoprotein found in normal neutrophils. The temporal correlation between specific p47 phosphorylation events and p47 translocation to membrane is consistent with a model of oxidase activation in which a series of p47 phosphorylation events which occurs in cytosol precedes and may be required for p47 interaction with membrane. PMID- 2246269 TI - Mannosidase II and the 135-kDa Golgi-specific antigen recognized monoclonal antibody 53FC3 are the same dimeric protein. AB - Monoclonal antibodies are frequently used as organelle-specific markers without identifying the specific antigen recognized. We have purified the protein recognized by a Golgi-specific monoclonal antibody 53FC3 (Burke, B., Griffiths, G., Reggio, H., Louvard, D., and Warren, G. (1982) EMBO J. 1, 1621-1628). Peptide microsequencing suggested that this antigen is mannosidase II, which was confirmed by cross-immunoprecipitation with an anti-mannosidase II antibody and by precipitation of mannosidase activity with the monoclonal antibody. Mannosidase II was found to exist normally as a disulfide-linked dimer. PMID- 2246271 TI - An inducible nuclear factor binds to a growth hormone-regulated gene. AB - Transcription of the serine protease inhibitor (Spi) 2.1 gene, a member of the serine protease inhibitor family, is induced by growth hormone (GH) in rat liver. To further study the mechanism involved in this process, we have isolated and characterized the Spi 2.1 gene from a rat genomic library. Examination of the 5' flanking region of the Spi 2.1 gene from normal animals revealed the presence of a DNase I hypersensitive site within 500 base pairs of the transcriptional initiation site, which was not detectable in hypophysectomized animals. Portions of the 5'-flanking region of the Spi 2.1 gene were fused to a heterologous promoter and reporter gene and introduced into primary rat hepatocytes by lipofection. Spi 2.1 sequences from -275 to -54 gave a 2-3-fold induction of reporter gene activity in cells grown in the presence of GH, similar to the level of induction of the endogenous Spi 2.1 mRNA in isolated hepatocytes. Further definition of the essential sequences revealed that a segment from -147 to -102 could confer GH responsiveness when linked in tandem copies in front of a heterologous promoter. Using the gel shift assay, a nuclear factor(s) from normal rat liver was identified which could interact with this minimal response fragment. The importance of this activity to GH regulation was suggested by the fact that it was absent in hypophysectomized animals but reappeared by 1 h after treatment of such animals with GH. The appearance of this activity was not blocked by pretreatment of animals with an inhibitor of protein synthesis, suggesting a preexisting factor is modified by GH to yield an activity which interacts with the Spi 2.1 gene. PMID- 2246270 TI - Differential inhibitory effects of lovastatin on protein isoprenylation and sterol synthesis. AB - It has been reported that when 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are utilized for treatment of hypercholesterolemia, as much as 50% inhibition of whole body cholesterol biosynthesis is observed. As general inhibitors of isoprenoid biosynthesis, these compounds can also inhibit the synthesis of the substituents of isoprenylated proteins. For two mammalian proteins (p21ras and lamin A), it has been demonstrated that such inhibition of biosynthesis of the isoprenoid substituent blocks proteolytic maturation of these proteins. It has been argued that advantage may be taken of this phenomenon to block the synthesis of p21ras in malignancies. It is also possible that treatment of hypercholesterolemia with lovastatin might produce problematic inhibition of protein processing dependent upon isoprenylation. In this report, we compare the concentration dependence of inhibition of isoprenylation dependent protein processing and sterol biosynthesis. Effects of partial inhibition of isoprenylated protein processing on whole cells can be sensitively assessed by visualization of lamina structure through indirect immunofluorescence. Our results indicate that the degree of inhibition of p21ras and prelamin A maturation by lovastatin is identical. Thus, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are unlikely to be useful as anti-malignancy drugs. However, the conditions of lovastatin treatment which produce 50% inhibition of sterol biosynthesis analogous to pharmacological conditions, produce no observable effects on isoprenylated protein maturation. PMID- 2246272 TI - Characterization of the 5'-flanking region of the rat protein kinase C gamma gene. AB - The 5'-flanking region of protein kinase C (PKC) gamma gene was identified from a rat liver genomic library in a bacteriophage lambda Charon 4A. A 3.6-kilobase (kb) genomic fragment containing the 5'-flanking region, first exon, and first intron was isolated and sequenced. The transcriptional initiation site, identified by S1 mapping and primer extension, was located 243 base pairs upstream from the translational initiation site. Promoter activity of a DNA segment spanning the 5'-flanking region was demonstrated by both in vitro transcription using HeLa cell nuclear extracts and chloramphenicol acetyltransferase assay by transfection of 293 cells with a PKC gamma-CAT fusion construct. Chloramphenicol acetyltransferase assay revealed that a fragment of about 0.16 kb from the transcriptional initiation site was sufficient for promoter activity in these cells, and the construct containing up to 1.6 kb from the cap site was expressed at a similar level. This promoter-active fragment contains several regions similar to defined transcriptional elements in other mammalian promoters, such as those for stimulatory protein 1 (Sp1), activator proteins 1 and 2 (AP1, AP2), c-myc, cAMP regulatory element-binding protein (CREB), and enhancer core (EnhC). Investigation of the genomic structure of PKC gamma gene may lead to the identification of cis-elements controlling tissue specific and developmental stage-specific expression of PKC gamma. PMID- 2246273 TI - Purification and biochemical characterization of statin, a nonproliferation specific protein from rat liver. AB - The nuclear protein statin, detectable with specific monoclonal antibodies, is found mostly in nonproliferating cells (Wang, E. (1985) J. Cell Biol. 100, 545 551). In the rat liver a 57-kDa protein designated as rat liver protein 57 (RLp57) was recently identified to carry the epitope for the anti-statin-specific monoclonal antibody, S-44 (Sester, U., Moutsatsos, I. K., and Wang, E. (1989) Exp. Cell Res. 182, 550-558). To characterize further the RLp57 protein, in the present study a polyclonal antibody was raised to the RLp57 protein eluted from polyacrylamide gel. Similar to the anti-statin monoclonal antibody, this polyclonal antibody recognizes a nuclear antigen in nonproliferating fibroblasts and reacts with a 57-kDa protein in rat liver and nonproliferating cells strongly suggesting that RLp57 is a statin protein from rat liver. Two isoforms of RLp57 (isoelectric points between 6.5 and 7.0) were detected after two-dimensional gel electrophoresis and immunoblotting. RLp57 was purified using multiple chromatographic steps, including ion-exchange and affinity chromatography followed by chromatofocusing. These results show that RLp57, a statin protein found in liver, has two isoelectric variants and can be purified to apparent homogeneity by sequential steps of chromatographic procedures. PMID- 2246274 TI - Fatty acylation of heparan sulfate proteoglycan from human colon carcinoma cells. AB - A number of transmembrane proteins have been recently reported to be modified by the covalent addition of saturated fatty acids which may contribute to membrane targeting and specific protein-lipid interactions. Such modifications have not been reported in cell-associated heparan sulfate proteoglycans, although these macromolecules are known to be hydrophobic. Here, we report that a cell surface heparan sulfate proteoglycan is acylated with both myristate and palmitate, two long-chain saturated fatty acids. When colon carcinoma cells were labeled with [3H]myristic acid, a significant proportion of the label was shown to be specifically incorporated into the protein core of the proteoglycan. Characterization of fatty acyl moiety in the purified proteoglycan by reverse phase high pressure liquid chromatography revealed that approximately 60% of the covalently bound fatty acids was myristate. We further show that this relatively rare 14-carbon fatty acid was bound to the protein core via a hydroxylamine- and alkali-resistant amide bond. The remaining 40% was the more common 16-carbon palmitate, which was bound via a hydroxylamine- and alkali-sensitive thioester bond. Palmitate appeared to be added post-translationally and derived in part from intracellular elongation of myristate, a process that occurred within the first two hours and was insensitive to inhibition of protein synthesis. Acylation of heparan sulfate proteoglycan represents a novel modification of this gene product and could play a role in a number of biological functions including specific interactions with membrane receptors and ligand stabilization. PMID- 2246275 TI - The tryptophan cluster: a hypothetical structure of the DNA-binding domain of the myb protooncogene product. AB - In the DNA-binding domain of the c-myb protooncogene product (c-Myb) which consists of three repeats of 51-52 amino acids, there are 3 perfectly conserved tryptophans in each repeat. Site-directed mutagenesis of these tryptophans showed that any single or multiple mutations of tryptophan to hydrophilic residues or alanine abolished or greatly reduced the sequence-specific DNA-binding activity, but mutations to hydrophobic amino acids retained considerable activity. Raman spectroscopic study showed that these tryptophans were buried in the protein core. These 3 tryptophans are proposed to form a cluster in the hydrophobic core in each repeat. This hypothetical structure is referred to as the "tryptophan cluster," and it may represent a characteristic property of a group of DNA binding proteins including the myb- and ets-related proteins. PMID- 2246276 TI - Eukaryotic and prokaryotic signal peptides direct secretion of a bacterial endoglucanase by mammalian cells. AB - It is well established that hydrophobic signal sequences direct proteins into or across the endoplasmic reticulum membrane in eukaryotes and cell membranes in prokaryotes. Although it is recognized that eukaryote proteins are efficiently secreted by bacterial systems, the export of bacterial proteins by eukaryotes has received little attention. To investigate membrane translocation of bacterial proteins by mammalian cells, the secretion of a bacterial endoglucanase (endoglucanase E) from stably transfected Chinese hamster ovary cells has been examined. We report that a functional endoglucanase is secreted when fused to prokaryote or eukaryote signal peptides. Furthermore, the endoglucanase was post translationally modified before secretion. Data presented in this paper suggest that secretion of bacterial proteins by eukaryote cells may be a general phenomenon and infer that there are no specific requirements with respect to the origin of the signal sequences. PMID- 2246277 TI - Analysis of the kinetic barriers for ligand binding to sperm whale myoglobin using site-directed mutagenesis and laser photolysis techniques. AB - Time courses for NO, O2, CO, methyl and ethyl isocyanide rebinding to native and mutant sperm whale myoglobins were measured at 20 degrees C following 17-ns and 35-ps laser excitation pulses. His64 (E7) was replaced with Gly, Val, Leu, Phe, and Gln, and Val68 (E11) was replaced with Ala, Ile, and Phe. For both NO and O2, the effective picosecond quantum yield of unliganded geminate intermediates was roughly 0.2 and independent of the amino acids at positions 64 and 68. Geminate recombination of NO was very rapid; 90% rebinding occurred within 0.5-1.0 ns for all of the myoglobins examined; and except for the Gly64 and Ile68 mutants, the fitted recombination rate parameters were little influenced by the size and polarity of the amino acid at position 64 and the size of the residue at position 68. The rates of NO recombination and ligand movement away from the iron atom in the Gly64 mutant increased 3-4-fold relative to native myoglobin. For Ile68 myoglobin, the first geminate rate constant for NO rebinding decreased approximately 6-fold, from 2.3 x 10(10) s-1 for native myoglobin to 3.8 x 10(9) s 1 for the mutant. No picosecond rebinding processes were observed for O2, CO, and isocyanide rebinding to native and mutant myoglobins; all of the observed geminate rate constants were less than or equal to 3 x 10(8) s-1. The rebinding time courses for these ligands were analyzed in terms of a two-step consecutive reaction scheme, with an outer kinetic barrier representing ligand movement into and out of the protein and an inner barrier representing binding to the heme iron atom by ligand occupying the distal portion of the heme pocket. Substitution of apolar amino acids for His64 decreased the absolute free energies of the outer and inner kinetic barriers and the well for non-covalently bound O2 and CO by 1 to 1.5 kcal/mol, regardless of size. In contrast, the His64 to Gln mutation caused little change in the barrier heights for all ligands, showing that the polar nature of His64 inhibits both the bimolecular rate of ligand entry into myoglobin and the unimolecular rate of binding to the iron atom from within the protein. Increasing the size of the position 68(E11) residue in the series Ala to Val (native) to Ile caused little change in the rate of O2 migration into myoglobin or the equilibrium constant for noncovalent binding but did decrease the unimolecular rate for iron-O2 bond formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2246278 TI - Expression of novel DNA-binding protein with zinc finger structure in various tumor cells. AB - We have isolated from B16 mouse melanoma cells a complementary DNA (Mel-18), whose deduced amino acid sequence possesses a characteristic zinc finger structure. Immunostaining with antibodies raised against partial Mel-18 peptide sequences demonstrated nuclear localization of the gene product. We have also demonstrated that this protein has DNA-binding capacity, and the zinc finger is responsible for the DNA binding. At the transcriptional level the Mel-18 mRNA was detected in all tumor cells examined as well as melanoma cells (ontogenically of neural origin) but was scarcely present in normal tissues except neural organs. The transcript is developmentally regulated. These data suggest that Mel-18 may play a role in transcriptional regulation and also in control of cell proliferation and/or neural cell development. PMID- 2246280 TI - Perichondral grafting for cartilage lesions of the knee. AB - Twenty-five patients with 30 chondral lesions of the knee were treated with an autogenous strip of costal perichondrium. The graft was fixed to the subchondral bone with Tissucol (Immuno, Vienna), a human fibrin glue. The leg was then immobilised for two weeks followed by two weeks of continuous passive motion. Weight-bearing was permitted after three months. The mean knee score (Ranawat, Insall and Shine 1976) changed from 73 before operation to 90 one year after; in 14 patients evaluated after two years there was no decrease. In 28 cases the defect was completely filled with tissue resembling articular cartilage. We conclude that in most cases perichondral arthroplasty of cartilage defects of the knee gives excellent results. PMID- 2246279 TI - Reconstitution of steps in the constitutive secretory pathway in permeabilized cells. Secretion of glycosylated tripeptide and truncated sphingomyelin. AB - The constitutive secretory pathway has been reconstituted in mechanically permeabilized Chinese hamster ovary cells using two secretory markers, an acyltripeptide (N-octanoyl-Asn-Tyr-Thr-NH2) that is glycosylated at Asn in the endoplasmic reticulum and a truncated ceramide that is converted to sphingomyelin. Secretion of these bulk phase markers is dependent on cytosolic proteins and ATP. Secretion of both the glycosylated tripeptide and truncated sphingomyelin was inhibited at 15 degrees C. These results are taken as evidence that the vesicle flow to the plasma membrane (rather than artificial lysis of endoplasmic reticulum or Golgi cisternae) is required for the release of markers to the medium. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a nonhydrolyzable analogue of GTP, inhibited secretion, resulting in an accumulation of both the glycosylated tripeptide and truncated sphingomyelin in the semi-intact cell. Inhibition of secretion by GTP gamma S was not observed in the presence of the aminoglycoside antibiotic neomycin. PMID- 2246281 TI - Assessing the results of hip replacement. A comparison of five different rating systems. AB - One hundred hips in patients who had had primary uncemented replacements were followed up for one or two years, and assessed by five different methods. All produced different results. The Hospital for Special Surgery rating produced the most optimistic assessment and the Merle d'Aubigne rating the most pessimistic. The functional class of the patients, as defined by Charnley in 1979, significantly affected the ratings, and these should clearly be included in all rating systems. Moreover, if systems are to be compared, they should all use descriptive words, such as limp or pain, in precisely the same way. PMID- 2246282 TI - Osteotomy for osteoarthritis of the hip. A survivorship analysis. AB - We have reviewed 368 osteotomies carried out for osteoarthritis of the hip at the Nuffield Orthopaedic Centre. Survivorship analysis showed that 10 years after osteotomy 47% had required no further surgery, and even after 20 years 23% had still not had a hip replacement. Hips with moderate arthritic change showed significantly better results than those with more severe degeneration. Osteotomies with varus angulation as well as medial displacement showed longer survival. PMID- 2246283 TI - The saddle prosthesis for salvage of the destroyed acetabulum. AB - We report the 12 to 74 month results of our mark I saddle prosthesis after its use as a salvage device for gross loss of pelvic bone stock in 76 patients with failed hip arthroplasties. The implant transmits load between iliac bone and bare polish chrome-cobalt. Our clinical and radiological results indicate that a useful and stable articulation can be achieved in most cases, provided that continued deep infection can be avoided. The appearance of radiological sclerosis at the bearing site in successful cases seems to indicate that significant late migration will not occur. Based on our experience with the mark I prosthesis we have designed and developed a mark II model which has freedom of axial rotation of the saddle. Our early results in 40 cases show a significant improvement over the results which could have been predicted for the mark I device. PMID- 2246284 TI - Intra-osseous pressure and oxygen tension in avascular necrosis and osteoarthritis of the hip. AB - The intra-osseous pressure, PO2, and PCO2 were measured in 32 hips (21 patients) which were painful but showed no severe degenerative changes. Pre-operative scintigraphy and radiography was performed in all patients. Thirteen hips showed early osteoarthritis, eight had early osteonecrosis, and 11 had no changes. Core biopsies were performed and the bone was examined histologically and graded for necrosis. Histologically, necrosis was present in 27 specimens. Scintigraphic findings did not correlate with the histological results but were more closely related to the radiographic findings. The intra-osseous pressure in hips with histological necrosis (mean 47 mmHg) was significantly higher than in hips without necrosis (mean 26 mmHg). The PO2 was lower in bone with histological necrosis (mean 44 mmHg) than in bone without (mean 71 mmHg). PO2 increased and intra-osseous pressure decreased after decompression. The results confirm that ischaemia plays a central role in the development of necrotic changes in bone. Histological necrosis was found in hips with radiographic signs of osteonecrosis and in those with osteoarthritis. Radiography, and scintigraphy are shown to be insensitive methods for differentiating between those disorders. PMID- 2246285 TI - Biomechanical strength of non-vascularised and vascularised diaphyseal bone transplants. An experimental study. AB - We studied the healing and torsional strength of non-vascularised (28) and vascularised (28) sections of tibial diaphyses in 56 cats. Both types of graft achieved fracture union in the same period of time, and at 12 and 16 weeks the non-vascularised grafts were as strong as the vascularised grafts. PMID- 2246286 TI - Replacing the medial collateral ligament with an allogenic tendon graft. An experimental canine study. AB - In order to determine whether an allogeneic tendon could be used to replace an extra-articular ligament, the right medial collateral ligament from 11 adult dogs was replaced with a fresh-frozen allogeneic patellar tendon. At each of 3, 6, 15, 30 and 52 weeks postoperatively, one dog was killed for micro-angiographical and histological studies; at 52 weeks the remaining six dogs were killed for tensile testing. Micro-angiograms showed that the allogeneic tendon was revascularised with infiltration of the mesenchymal cells from the surrounding tissues and both ends of the graft. Histologically, the alignment of the fibroblasts and collagen bundles became more regular over time, without any immunological rejection. A biomechanical study performed at 52 weeks found no significant difference in stiffness or ultimate load between normal and reconstructed ligaments. Fresh frozen allogeneic tendons are therefore considered useful for extra-articular ligament reconstruction. PMID- 2246287 TI - Open reduction and fixation of proximal humeral fractures and fracture dislocations. AB - Open reduction and internal fixation was employed in the treatment of 25 severely displaced fractures and fracture-dislocations of the proximal humerus. Our aims were accurate reduction and stable fixation to allow early mobilisation and to achieve full functional recovery. In 15 fractures an AO T-plate was used and in 10 a bent semitubular plate was employed as a blade plate. Excellent or satisfactory results were obtained in all six patients with two-part fractures involving the surgical neck; in four of the five patients with three-part fractures involving the surgical neck and tuberosities; in nine of the 11 patients with fracture-dislocation; and in two of the three patients with split fractures of the humeral head. Overall results were good or satisfactory in 21 of the 25 cases. Unsatisfactory results were associated with rotator cuff damage. PMID- 2246288 TI - Results of a 25-year screening programme for neonatal hip instability. AB - From 1962 to 1986, 117,256 neonates were screened for congenital dislocation of the hip (CDH). When the primary physical examination was performed by the junior paediatric staff there was a persistent late diagnosis rate of 0.5 per 1000 live births. When the primary examination was undertaken by experienced orthopaedic personnel (1982 to 1984) the late diagnosis rate fell and fewer infants were splinted. PMID- 2246289 TI - Development of the hip in multiple epiphyseal dysplasia. Natural history and susceptibility to premature osteoarthritis. AB - We have determined the natural history of hip development in 42 patients with multiple epiphyseal dysplasia (MED). Premature osteoarthritis was a frequent outcome and was almost inevitable before the age of 30 years in those with incongruent hips. There were two types of immature hips: type I, the more severe form, had a fragmented and flattened ossific nucleus and acetabular dysplasia, was misshapen at skeletal maturity and osteoarthritic by 30 years of age; the milder type II hip had a small, rounded, uniformly ossified nucleus and a more normal acetabulum. Type II hips were well formed at maturity and were less prone to premature osteoarthritis. Considerable variations were noted in the manifestations of MED between families but not within families. The prognosis of a child's hip could be predicted; in sporadic cases from the type of immature hip, and in familial cases by also taking into account the outcome of affected relatives. PMID- 2246290 TI - Modified Van Nes rotationplasty for osteosarcoma of the proximal tibia in children. AB - Above-knee amputation has been the traditional treatment for osteosarcoma of the proximal tibia. Recent advances in chemotherapy have encouraged the development of limb-salvage techniques. Van Nes rotationplasty for malignant lesions of the distal femur has increased in popularity as a reconstructive technique, but no similar procedure has been described for lesions of the proximal tibia. We have developed a modified rotationplasty for this lesion and have performed it in four children. The surgical technique, postoperative management and results of the procedure are described. Two patients had delayed wound healing. No other complications have developed and our patients were disease-free at follow-up, while the appearance of the leg was well accepted by the patients and their parents. This procedure is a useful addition to the armamentarium of the tumour surgeon for the treatment of malignant lesions of the proximal tibia. PMID- 2246291 TI - Failed acromioplasty for impingement syndrome. AB - We evaluated 67 shoulders in 65 patients who had pain and dysfunction for more than two years after an initial acromioplasty for impingement syndrome without a rotator cuff tear. In addition to a thorough history, physical examination, local anaesthesia injection and any other necessary investigations all patients had arthroscopic evaluation of the shoulder. In 27 shoulders there had been diagnostic errors, and in 28 operative errors; only in 12 had the diagnosis and the operative procedure both been correct. Subsequent operative intervention in patients not receiving worker's compensation benefit had a 75% success rate, whereas in those receiving such benefits the success rate was only 46%. PMID- 2246292 TI - Extending intramedullary rods in congenital pseudarthrosis of the tibia. AB - Five patients with Boyd type II congenital pseudarthrosis of the tibia underwent excision of the pseudarthrosis and double onlay bone grafting. Stability was maintained by extending intramedullary rods. Clinical union was achieved in all cases at a mean of 8.6 months (range six to 11). The rods extended by 15.7% (range 2% to 31.4%) as growth occurred. One rod was removed because of infection and a vascularised free fibular graft was subsequently performed. The extending rods provided stability while union occurred and did not require revision as the legs grew. The rods can be removed easily and have not jeopardized further surgical options. PMID- 2246293 TI - Arthroscopic use of the Herbert screw in osteochondritis dissecans. PMID- 2246294 TI - Adolescent idiopathic scoliosis in identical twins. PMID- 2246295 TI - Irreducible acute anterior dislocation of the shoulder: interposed scapularis. PMID- 2246297 TI - An assessment of assessment. PMID- 2246296 TI - Irreducible acute anterior dislocation of the shoulder: interposed bicipital tendon. PMID- 2246298 TI - Parosteal osteosarcoma. Treatment by wide resection and prosthetic replacement. AB - We have reviewed 20 cases of parosteal osteosarcoma treated by wide local resection and prosthetic replacement and followed up for six to 17 years. Limb function was excellent in 85%. One patient with grade III histological disease developed pulmonary metastases. Four patients had local recurrences, which were related to repeated preliminary biopsies, inappropriate siting of biopsy and vascular encroachment by the tumour. After this mode of treatment, the outcome was not related to medullary invasion by the tumour. PMID- 2246299 TI - Bone lysis in well-fixed cemented femoral components. AB - We have reviewed 25 cases of focal femoral osteolysis in radiographically stable, cemented femoral implants. In three hips retrieved at post-mortem from two patients, we have been able to make a detailed biomechanical and histological analysis. The interval between arthroplasty and the appearance of focal osteolysis on clinical radiographs ranged from 40 to 168 months, and in over 70% of the cases this did not appear until after five or more years. Few had significant pain and there was no relation to age, sex or original diagnosis. The most common site for osteolysis were Gruen zones 2 and 3 on the anteroposterior radiograph and zones 5 and 6 on the lateral radiograph. In 15 cases (60%), the area of osteolysis corresponded to either a defect in the cement mantle or an area of very thin cement. The rate of progression of these lesions was variable, but to date only one has progressed to gross loosening of the femoral component. The back-scatter scanning electron microscopic examination of serial sections and biomechanical testing of the post-mortem specimens demonstrated focal cement fracture around implants that were otherwise rigidly fixed. In eight cases from which tissue was available, histology showed a histiocytic reaction with evidence of particulate polymethylmethacrylate. We consider that this local fragmentation was the stimulus for local osteolysis in an otherwise stable cemented femoral component. PMID- 2246300 TI - Localised endosteal bone lysis in relation to the femoral components of cemented total hip arthroplasties. AB - Four cases are described of localised endosteal bone lysis in the femur occurring in association with cemented femoral components that were not obviously 'loose' radiologically. In each, the area of lysis was shown at operation to be related directly to a region in which there was a local defect in the cement mantle surrounding the stem. Via the space between the stem and cement, such defects provide a route through which the contents of the joint cavity may reach the endosteal surface of the femur, subsequently leading to localised bone lysis, and later to frank loosening. PMID- 2246301 TI - Aggressive granulomatous lesions in cementless total hip arthroplasty. AB - We describe six patients with aggressive granulomatous lesions around cementless total hip prostheses. Two patients previously had a cemented prosthesis in the same hip. The Lord prosthesis was used in five patients, the PCA in one. Both prostheses were made of chrome-cobalt alloy. Pain on weight-bearing occurred on average 3.2 years after the cementless arthroplasty, and at that time radiography revealed aggressive granulomatosis around the proximal femoral stem and the acetabular component in five of the patients; one had a large solitary granuloma in the proximal femur. Revision was performed on average 4.8 years after the cementless arthroplasty. At that time all granulomas had grown large in size; while waiting for revision operation, two femoral stem components fractured. All the granulomas showed a uniform histopathology, which included histiocytosis; the cause for these lesions was thought to be plastic debris from the acetabular socket. PMID- 2246302 TI - Reduction of contamination at total hip replacement by special working clothes. AB - We assessed wound, air and operative field contamination at 50 total hip operations, performed in a zonal ventilation system. Theatre staff wore either a specially designed polypropylene non-woven coverall or conventional cotton shirt and trousers. The surgeons wore partially impermeable operating gowns. The polypropylene coverall was associated with significantly lower air and wound counts. The coverall was warmer than cotton but judged to be acceptable. The combined use of zonal ventilation and the coverall achieved ultra-clean air conditions. PMID- 2246303 TI - Macrophages stimulate bone resorption when they phagocytose particles. AB - We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene. PMID- 2246304 TI - Why use drains? AB - There is no firm published evidence to support the use of closed suction drains. Over 20 years ago, large studies by the Public Health Laboratory Service and the National Research Council found that drains were risk factors for wound infection. A prospective randomised study of the use of closed suction drains after surgery for fractured neck of femur in 70 patients failed to show that drains improved wound healing. Drained cases had more complications. PMID- 2246305 TI - Cup containment and orientation in cemented total hip arthroplasties. AB - We reviewed the radiographs of 864 Charnley and STH (Zimmer) cemented total hip arthroplasties with a mean follow-up of seven years (maximum 16 years). Survivorship analysis was used to assess the correlation between radiographic performance and the bony containment or the coronal orientation of the acetabular cup. The cup orientation and containment were interrelated; all vertically oriented cups were completely contained, whereas 25% of more horizontal cups were only partially contained. Completely contained cups had significantly lower incidences of complete cement-bone radiolucency (p = 0.02) and of wear (p = 0.09). Vertically oriented cups had a lower incidence of continuous radiolucency than neutrally oriented cups, but this was not statistically significant (p = 0.25). Our results confirm the importance of complete bony containment, and also indicate that it is better to accept vertical orientation and obtain full bony coverage than to have a more horizontal orientation with partial containment. PMID- 2246306 TI - Education--our main theme. The 1990 presidential address to the American Burn Association. PMID- 2246307 TI - Morphine pharmacokinetics during anesthesia and surgery in patients with burns. AB - The plasma clearance, plasma half-life, and apparent volume of distribution of morphine during anesthesia and surgery were determined in seven patients with burns and compared with seven age-matched control subjects. The burn group had a significantly lower clearance, longer terminal half-life, and smaller volume of distribution than the control group. The clearance was 12 +/- 2 ml/min/kg, the half-life was 123 +/- 24 minutes, and the volume of distribution was 2.2 +/- 0.4 L/kg for the subjects with burns compared with 25 +/- 3 ml/min/kg, 89 +/- 18 minutes, and 3.2 +/- 0.8 L/kg for the control subjects (p less than 0.001, less than 0.02, and less than 0.02, respectively). These data contrast with the theory that patients with burns have a tolerance to narcotics and suggest the need for further study of the pharmacologic effects of burn injury and surgery. PMID- 2246308 TI - Effects of acute ethanol ingestion and burn injury on serum immunoglobulin. AB - Previous studies have found that acute ethanol ingestion before burn injury caused further impairment of mitogenic response of B lymphocytes compared with burn injury alone. The principal role of B lymphocytes is immunoglobulin production. This study was designed to determine the effect of acute ethanol ingestion on circulating immunoglobulin levels before injury. Serum concentrations of IgG, IgM, and IgA in rats were measured with the use of radial immunodiffusion plates at 4 days after a 30% burn injury in animals that had received a single ingestion of 3.0 ml ethanol per kilogram of body weight. The immunoglobulin levels were compared with appropriate controls. A 30% burn injury produced significant decreases in serum IgG and IgA levels but not in IgM levels, whereas acute ethanol ingestion only decreased IgA levels. Acute ethanol ingestion before injury did not induce any further significant decrease than did burn injury alone. PMID- 2246309 TI - Comparison of resting energy expenditures and caloric intake in children with severe burns. AB - Nutritional support is provided to children after severe burn injuries in amounts derived from empirical formulas or measurements of resting energy expenditure. To scrutinize these methods, indirect calorimetry measurements were performed on 74 survivors of burns (greater than or equal to 40% total body surface area) and compared to their actual caloric intake, percent weight change, and optimal caloric requirements formulated from the Curreri and Shriners' equations. These parameters showed that in spite of an initial deficit in actual caloric intake as compared to formulated goals, weight was maintained, whereas resting energy expenditures ranged from 30% to 40% below the actual caloric intake. Furthermore, a subgroup of patients (n = 42) who met +/- 20% of their formulated needs were stratified by extent of burn; this illustrated a significant weight gain in the more severely burned children. In conclusion, nutritional formulas in popular use overestimate caloric requirements in severe burns, whereas resting energy expenditure measurements require an additional factor of 30% to maintain body weight. PMID- 2246310 TI - Cyclosporine A for prolonging allograft survival in patients with massive burns. AB - Cyclosporine A (CsA) immunosuppression was used in three patients with massive burns to prolong skin allograft survival. Cyclosporine A kinetic studies in patients with burns revealed markedly accelerated blood clearance and high variability in drug absorption when compared with studies in renal transplantation patients. Doses required to maintain therapeutic levels varied widely. While patients were receiving adequate maintenance therapy with CsA immunosuppression the allograft was tightly adherent without gross or microscopic rejection and was indistinguishable from autograft. Ultimately, patients' wounds were permanently covered with sequential autografts by recropping limited donor sites. There were not unusual septic complications, although prophylaxis for opportunistic infections was used. The disadvantage of allograft use is its early rejection and obligatory replacement until permanent coverage with autograft can be accomplished. Cyclosporine A can prolong allograft survival and allow autograft coverage from limited donor sites in a sequential fashion. This may lead to increased survival in patients with massive burns. PMID- 2246311 TI - The efficacy of pediatric blood culture sets in the determination of burn bacteremia. AB - A blood culture is an essential laboratory procedure necessary to confirm a septic episode. However, it is important to collect the blood sample at the appropriate time with an acceptable technique. The standard method is to collect at least 5 to 10 ml blood per culture bottle from patients with fevers. However, this volume of blood is an unrealistic amount to take from the frequently febrile pediatric patient. Alternatively, the pediatric blood culture bottle allows the collection of 1 ml blood per bottle to perform the same evaluation. We evaluated the two techniques of blood-culture collection over a 9-month period and compared the results between adult and pediatric blood culture bottles. Seventy-six patients, from November 1988 through February 1989, had blood cultures performed with the adult culture bottles, which produced a total of 1314 samples. A total of 113 patients, from March through July 1989, had blood cultures performed with the pediatric culture bottles, which produced a total of 758 samples. Percent recovery for the adult bottles versus the pediatric bottles was 13.95% versus 22.8% (p less than 0.0001). Since the amount of blood necessary to isolate an infectious agent is critical not only for laboratory identification but also for the volume of blood of pediatric patients, these data clearly establish the efficacy of pediatric blood culture bottles and the utilization of smaller amounts of blood. Not only did this approach significantly enhance organism recovery rate, but it may well be more cost-effective because fewer cultures need to be performed to isolate the infectious organism. PMID- 2246312 TI - A survey of wound monitoring and topical antimicrobial therapy practices in the treatment of burn injury. AB - A survey was done to determine how burn wound microbial monitoring is performed and how topical antimicrobial agents are employed. The survey was sent to 90 burn care facilities, which comprised most of the major burn centers in the United States. The survey contained questions concerning frequency and techniques of wound monitoring, personnel involved in monitoring, as well as questions about how decisions were made to initiate topical antimicrobial therapy, which agents were selected, and how they were administered. Sixty of 90 facilities (66%) responded to the survey. Although there were few areas of unanimous agreement, several trends did emerge. Most facilities monitored burn wounds for microbes (92%). Wound monitoring was typically done at least twice weekly by either surface swab or quantitative biopsy. Nursing staff played a significant role in specimen collection in 69% of facilities and were solely responsible for obtaining biopsy specimens in 29% of facilities that used biopsies exclusively. All responding facilities used topical antimicrobial agents; silver sulfadiazine was the most popular (95%). Only 33% of facilities surveyed had their own laboratory for microbial monitoring. Rapid techniques for early diagnosis of wound sepsis were used in 20% of units, and topical antimicrobial testing was used in 17% of facilities surveyed. PMID- 2246313 TI - The use of intestinal antibiotics to delay or prevent infections in patients with burns. AB - Bacterial colonization and infection of wounds in seriously burned patients often comes from the patient's indigenous bowel flora. A prospective randomized clinical trial that involved 30 patients with 20% or greater total body surface area burns was undertaken to evaluate the use of a standard antibiotic bowel preparation in the delay or prevention of bacterial colonization of the burn wound and sepsis. Certain enteric bacteria were seen less frequently in the treated group (Enterobacter organisms), but other bacteria appeared more often in the treated group (Proteus organisms and enterococci). The average time of colonization of the burn wounds was 6.1 days in the treated group and 6.7 days in the control group. Blood cultures were positive for enteric organisms earlier in the treatment group. Pseudomonads appeared earlier in the wound and blood cultures of the treated group than in the control group. The effect of antibiotic bowel suppression in patients with burns is varied and unpredictable. The bowel preparation may select certain organisms and lead to earlier colonization of the wounds. Overall outcome and survival was not improved by the use of an antibiotic bowel preparation in these patients. PMID- 2246314 TI - Tissue-expanded radial forearm free flap in neck burn contracture. AB - Neck contracture after burn injury can result in severe functional as well as aesthetic deformities. Contracture can recur even after wide and complete release and full-thickness skin grafting. Recurrence is partly due to the inherent difficulties in both early postoperative immobilization and the required long term splinting. When adjacent tissues are also burned, adequate local tissue for reconstruction may not be available; therefore, free-tissue transfer may be necessary. The large surface area that is required after adequate release may be provided by tissue expansion before free-tissue transfer. In the case presented the use of tissue-expanded radial forearm free flap for the reconstruction of a recurrent neck contracture is described. PMID- 2246315 TI - Gasoline burns: the preventable cause of thermal injury. AB - Gasoline related burns are a significant cause of thermal injuries each year in the United States. In this retrospective review of 1858 admissions to our Regional Burn Center from 1979 to 1988, 270 (14.5%) were persons with gasoline related injuries. Natural gas and other distillates were excluded. Most victims were male (228 of 270); mean age was 27 years; mean burn size was 25% total body surface area. There were 299 skin grafts performed on 172 patients, and there were 16 deaths. The mean length of stay decreased from 38 to 17 days (p less than 0.001) between the first and second 5-year time periods, even though there was no significant change in age or mean burn size. The majority (59%) of gasoline related burns were the result of inappropriate or unsupervised use of gasoline. The general public is largely unaware of the dangers of gasoline, and further education in this area is needed. PMID- 2246316 TI - Carburetor burns: preventable injuries associated with high morbidity and frequent litigation. AB - We have identified carburetor burns as a significant cause of preventable morbidity, both from long-term functional and cosmetic standpoints. The epidemiology of carburetor burns and our experience are described. All of our patients were male, with a mean age of 35 years. Average burn size was 11.3%. The anatomic distribution of these burns, most often on the dominant hand and on the face, contributes to the morbidity of these burns. This injury has been associated with increasingly frequent litigation. We believe that an active education campaign and the addition of warning labels to car engine compartments would make an impact in decreasing the incidence of carburetor burns. PMID- 2246317 TI - Marjolin's ulcer: a review and reevaluation of a difficult problem. AB - The formation of an epidermoid carcinoma in nonhealing scar tissue, a Marjolin's ulcer, is a well described neoplasm. These lesions are, however, frequently overlooked and often inadequately treated. This paper reviews six cases of scar tissue carcinoma. All lesions were secondary to various kinds of burns. Four of the Marjolin's ulcers were well-differentiated squamous cell carcinomas. One was a moderately differentiated squamous cell carcinoma, and one was a malignant melanoma. The average age at presentation was 59 years, and the mean interval from time of burn injury to appearance of neoplasm was 36.8 years. The lesions varied in anatomic location and involved the upper extremities, lower extremities, and scalp. In addition to the case studies, this paper reviews the literature and provides a logical treatment plan for a patient with a Marjolin's ulcer. Because these lesions can be very aggressive, a well thought-out treatment plan is necessary to optimize care and assure patient survival. PMID- 2246318 TI - Discharge videotaping: a means of augmenting occupational and physical therapy. AB - Regional burn centers commonly receive patients from medical facilities that are geographically distant. Logistic problems that may hamper follow-up care in the burn center can lead to a decrease in function as a result of contractures and hypertrophic scar formation. Inexperience on the part of therapists at community facilities serves to intensify this problem. Discharge videotaping, with respect to physical and occupational therapy programs, is a means of documenting range of motion at the time of discharge and providing visual documentation of the therapy program to be followed on an outpatient basis. The video tapes are forwarded to the outlying community hospital's therapy department in order to accomplish these goals. PMID- 2246319 TI - Familial values as factors influencing long-term psychological adjustment of children after severe burn injury. AB - This study replicates earlier findings that children who survive severe burn injury do make positive psychological adjustment. Family support and a family value of autonomy were predicted to be critical variables in promotion of psychological adjustment. In addition, the study presents the hypothesis that length of time after burn injury and level of intelligence are contributing factors in psychological adjustment. Forty-four adolescents with a mean of 60% total body surface area (TBSA) full-thickness burns were studied. Half of the subjects scored within the normal range on a measure of psychological adjustment. Familial value patterns were critical in the prediction of psychological adjustment. Positive psychological adjustment was predicted by greater family cohesion, independence, and more open expressiveness within the family. Level of intelligence did not contribute to adjustment. Length of time after injury, if it is important to psychological healing, appears to be a factor only during the initial 2 years after burn injury. PMID- 2246320 TI - The 1989 Everett Idris Evans memorial lecture: coming of age--the first twenty one years. PMID- 2246321 TI - The future of skin banking. PMID- 2246322 TI - The Journal of Cell Biology. 10-year author index. Volumes 84-109. 1980-1989. PMID- 2246323 TI - Stimulation of plasma membrane and matrix vesicle enzyme activity by transforming growth factor-beta in osteosarcoma cell cultures. AB - Transforming growth factor-beta (TGF beta) serves an important role in extracellular matrix formation by stimulating the production of numerous extracellular matrix proteins by connective tissue cells and by osteoblasts or bone-forming cells. TGF beta has been shown to stimulate alkaline phosphatase (ALPase) activity in the rat osteoblast-like osteosarcoma cell line ROS 17/2.8. Previous studies have shown that this enzyme is elevated during calcification of bone and that it is enriched in matrix vesicles, an extracellular organelle associated with initial hydroxyapatite formation. To test the hypothesis that TGF beta plays a role in regulating mineral deposition in the matrix, the effects of TGF beta on ALPase and phospholipase A2, two enzymes associated with mineralization, were examined. ROS 17/2.8 cells were cultured at high and low density with recombinant human TGF beta (0.1-10 ng/ml) to examine the influence of cell maturation on response to TGF beta. Maximal stimulation of ALPase activity in the low density cultures was seen at 5 ng/ml; in high-density cultures, there was further stimulation at 10 ng/ml. There was a dose-dependent increase in ALPase activity seen in the matrix vesicles and plasma membranes in both types of cultures. Matrix vesicle ALPase exhibited a greater response to factor than did the plasma membrane enzyme. However, in low-density cultures, the two membrane fractions exhibited a parallel response with greatest activity consistently in the matrix vesicles. There was a dose-dependent increase in phospholipase A2-specific activity in the plasma membranes and matrix vesicles of both high- and low-density cultures. In agreement with previous studies, TGF beta inhibited cellular proliferation 50%. The results show that addition of TGF beta stimulates the activity of enzymes associated with calcification. The effect of TGF beta is dependent on the stage of maturation of the cell. This study indicates that TGF beta may play an important role in induced bone formation, calcification, and fracture repair in addition to its role in promoting chondrogenesis. PMID- 2246324 TI - Reversal of lovastatin-mediated inhibition of natural killer cell cytotoxicity by interleukin 2. AB - The activation of human natural killer (NK) cell cytotoxicity by interleukin 2 (IL-2) is well established, although the biochemical mechanisms of this stimulation have not yet been fully delineated. Earlier, we reported that treatment of NK cells with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase such as compactin or lovastatin significantly abrogates the in vitro killing of a susceptible human erythroleukemic cell line and that this inhibition can be completely reversed by 2 hr of exposure to mevalonate (J. Cell. Physiology 139:550-557, 1989). We report here that 24 hr of treatment with IL-2 also reverses lovastatin inhibition of NK cell function. In addition to natural cytotoxicity, IL-2 also restores chemotactic and antibody dependent cellular cytotoxicity functions to lovastatin-treated cells. IL-2 does not stimulate proliferation of these cells during this time period, nor does it affect the phenotypic composition of the NK cell preparations. Although IL-2 was able to reverse the lovastatin-mediated inhibition of every cell function we examined, it had no effect on the inhibition of cholesterol biosynthesis as measured by [3H]acetate incorporation into non-saponifiable lipids, nor did it stimulate HMG CoA reductase activity. These findings support the hypothesis that there is a non sterol isoprenoid product which is required for NK cell cytotoxicity and chemotaxis. In addition, the data suggest that IL-2 stimulation of NK cells proceeds by an isoprenoid-independent pathway. PMID- 2246325 TI - Growth factor-induced DNA synthesis in cells that overproduce protein kinase C. AB - In previous studies (Housey et al.: Cell 52:343-354, 1988), our laboratory demonstrated that a cell line R6-PKC3 that stably overproduces high levels of the beta 1 isoform of PKC displayed several abnormalities in growth control, and these phenotypic changes were also markedly enhanced when the cells were exposed to TPA. The present studies indicate that these cells also display marked changes in their response to certain growth factors. A striking finding was that several agents when tested alone in serum-free medium, including EGF, PDGF, TPA, teleocidin, and OAG, stimulated DNA synthesis in quiescent R6-PKC3 cells but had a negligible effect in quiescent R6-C1 cells, a vector control cell line with normal levels of PKC. R6-PKC3 cells also show an exaggerated response to very low concentrations of serum, when compared to R6-C1 control cells. These studies provide direct genetic evidence that alterations in cellular levels of PKC can markedly influence the responses of cells to specific growth factors. PMID- 2246326 TI - Inhibition of gap-junctional intercellular communication and enhanced binding of fibronectin-coated latex beads by stimulation of DNA synthesis in quiescent 3T3 L1 cells. AB - To clarify the modulation of intercellular communication via gap junctions, associated with the growth induction of quiescent 3T3-L1 cells, we investigated the gap-junctional intercellular communication in growth-stimulated cells that were able to bind fibronectin-coated beads. When quiescent 3T3-L1 cells were incubated with fibronectin-coated beads for the first 2 h after the addition of calf serum, 24.0% of the cells bound and phagocytosed beads. Among the cells with bound beads, the percentage of the cells labeled concurrently with bromodeoxyuridine was 63.7% when examined 13 h after the addition of calf serum. Transient reduction of dye-coupling, measured with Lucifer Yellow CH, was observed only in the cells with bound beads 2 h after addition of calf serum, but it was not observed in the cells without bound beads. When the quiescent cells were incubated with fibronectin-coated beads for 2 h from 4-6 h after the addition of calf serum, the percentage of cells with bound beads increased to 53.1%, but the decrease in dye-coupling among the cells with bound beads was slight. These results suggest that the induction of cell growth causes a transient reduction in gap-junctional intercellular communication in 3T3-L1 cells with bound fibronectin-coated beads. PMID- 2246327 TI - Establishment of an osseous cell line from fetal rat calvaria using an immunocytolytic method of cell selection: characterization of the cell line and of derived clones. AB - Using selective media and complement-mediated lysis of primary cultures of a fetal rat calvarial cell population, we have developed a cell line (OBCK6) that exhibits osteoblastic characteristics. OBCK6 cells demonstrated enhanced parathyroid hormone (PTH)-stimulated adenylate cyclase activity relative to the primary calvarial population, production of alkaline phosphatase activity and type 1 collagen, and the capacity to form mineralized nodules in unsupplemented medium after prolonged (22-26 day) culture. Two sublines, CFK1 and CFK2, which were isolated by dilution cloning, differed morphologically and with respect to growth rate. CFK1 cells demonstrated high PTH and prostaglandin E2-stimulated adenylate cyclase activity, whereas only low PTH-stimulated activity was observed in CFK2 cells. Retinoic acid and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] each reduced PTH-stimulated adenylate cyclase activity in both the cell types. Retinoic acid and dexamethasone reduced and 1,25(OH)2D3 enhanced alkaline phosphatase activity in these cells. PTH significantly augmented alkaline phosphatase activity to a much greater extent in CFK1 than in CFK2 cells. Both CFK1 and CFK2 cells expressed type I but type III collagen, and neither expressed osteocalcin. Strong Alcian blue staining of CFK2 cells was suggestive of a cartilaginous phenotype. These three cell lines, therefore, demonstrated discrete characteristics of skeletal cell function and should provide important models for evaluation of mechanisms of mineralization and for control of skeletal cell growth and mesenchymal differentiation in vitro. PMID- 2246328 TI - Vitamin D regulates transferrin receptor expression by bone marrow macrophage precursors. AB - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is known to prompt monocytic differentiation of a variety of leukemic lines. We previously extended these observations to non-transformed bone marrow macrophage precursors by demonstrating that the steroid enhances plasma membrane expression of the macrophage-specific mannose-fucose receptor (Clohisy et al., J Biol Chem 262:15922-15929, 1987). Because this membrane protein is involved in non-opsonin mediated endocytosis, these observations raised the possibility that 1,25(OH)2D3 globally upregulates endocytic receptors. The present study, aimed at addressing this issue, turns to the transferrin receptor as a paradigm for endocytic receptors and explores the impact of 1,25(OH)2D3 on its expression. We found that in contrast to the mannose-fucose receptor, plasma membrane transferrin receptor expression by bone marrow-derived macrophage precursors declines by at least 30% in a dose-dependent fashion with exposure to 1,25(OH)2D3. The effect reflects diminished receptor capacity with no change in Kd, and is independent of cell cycle. Moreover, while Vmax of receptor-ligand internalization mirrors plasma membrane occupancy, Kuptake remains unaltered in the presence of vitamin D3, indicating that the down-regulating event does not reflect on enhanced rate of endocytosis. Further, pulse chase experiments show parallel cell surface, intra cellular, and medium redistribution of radioligand with time steroid-treated and control cells. In a similar vein, while total cell-associated radioligand falls in the presence of vitamin D3, the percentage of intracellular and surface bound counts at equilibrium are constant in both groups. Finally, immunoprecipitation studies reveal that the down-regulating effects of 1,25(OH)2D3 cannot be explained by inhibition of transferrin receptor synthesis. Thus, the decrease in total cellular transferrin binding sites is likely to represent either enhanced degradation or synthesis of "cryptic" receptors which fail to recognize 125I transferrin. PMID- 2246329 TI - Basic fibroblast growth factor accumulates in the nuclei of various bFGF producing cell types. AB - The intracellular localization of basic fibroblast growth factor (bFGF) was studied in BHK-21 cells transfected with an expression vector containing the complementary DNA (cDNA) of the human bFGF gene (pbFGF). The intracellular location of bFGF was determined using indirect immunofluorescence. The antibodies used were polyclonal antibodies directed against either recombinant human bFGF or recombinant Xenopus bFGF. The nuclei of transfected cells that produce bFGF, but not the nuclei of untransfected cells, were labeled strongly by the antibodies. The nuclear staining was totally abolished when anti-bFGF antibodies preadsorbed with bFGF were used. Several types of endothelial cells known to produce bFGF were also stained in their nuclei by the antibodies. Nuclear extracts prepared from transfected cells were found to contain bFGF as determined using heparin sepharose affinity chromatography, followed by Western blot analysis of fractions, which stimulated the proliferation BHK-21 cells. The mitogenic activity associated with the nuclei was not destroyed when isolated cell nuclei were digested by trypsin. It is therefore likely that the nucleus associated bFGF is intranuclear. These findings suggest that some biological activities of bFGF may be mediated by nuclear bFGF binding proteins or by the direct binding of bFGF to DNA. PMID- 2246330 TI - Characterization of the D-allose-mediated regulation of sugar transport in Chinese hamster fibroblasts. AB - Exposure to D-allose has been demonstrated to lead to decreased 2-deoxy-D-glucose (2-DG) and 3-0-methyl-D-glucose transport in the V79 Chinese hamster lung fibroblast cell line. The effect of D-allose 1) was maximal after 4 hours exposure to the cells; 2) was optimal between 2.77 and 5.55 mM D-allose; and 3) led to a decreased Vmax for 2-DG transport with no change in the transport Km value. The decrease in 2-DG transport induced by D-allose was reversible and the reversal was differentially affected by cycloheximide, being blocked by a low concentration of cycloheximide (0.05 micrograms/ml) but not a high concentration of the inhibitor (5 micrograms/ml). D-allose did not competitively inhibit the transport of 2-DG while D-glucose under similar conditions yielded a Kl for 2-DG transport inhibition of 1.7 mM. Additionally, D-allose did not affect the phosphorylation of 2-DG by hexokinase in cell-free cytosol. The data indicate that D-allose has significant lowering effects on sugar transport activity. Additionally, while the sugar itself may be the active component in sugar transport regulation, the effect is not blocked by inhibition of protein synthesis but the synthesis of a regulatory protein(s) may be involved in the return of sugar transport following D-allose removal. PMID- 2246331 TI - Correlation between redistribution of a 26 kDa protein and development of chronic thermotolerance in various mammalian cell lines. AB - Previous studies suggested that a 26 kDa protein might play an important role in protein synthesis-independent thermotolerance development in CHO cells. To determine if this phenomenon was universal, four mammalian cell lines, viz., CHO, HA-1, murine Swiss 3T3, and human HeLa, were studied. Cells were heated at 42 degrees C, and the level of 26 kDa protein in the nucleus was measured, together with clonogenic survival and protein synthesis. The results demonstrated that 1) the 26-kDa protein was present in the four different cell lines, and 2) the level of the 26 kDa protein in their nuclei was decreased by 30-70% after heating at 42 degrees C for 1 hr. However, restoration of this protein occurred along with development of chronic thermotolerance. The protein synthesis inhibitor cycloheximide (10 micrograms/ml) neither inhibited the development of chronic thermotolerance nor affected the restoration of the 26 kDa protein in the nucleus. In fact, this drug protected cells from hyperthermic killing and heat induced reduction of 26 kDa protein in the nucleus. Heat sensitizers, quercetin (0.1 mM), 3,3'-dipentyloxacarbocyanine iodide (DiOC5[3]: 5 micrograms/ml), and stepdown heating (45 degrees C-10 min----42 degrees C), potentiated hyperthermic killing and inhibited or delayed the restoration of the 26 kDa protein to the nucleus. These results support a correlated, perhaps causal relationship between the restoration of the 26 kDa protein and chronic thermotolerance development in four different mammalian cell lines. PMID- 2246332 TI - Estrogen regulates peptidylarginine deiminase levels in a rat pituitary cell line in culture. AB - A Nonidet P-40 extract of growth hormone-producing rat pituitary MtT/S cells was found to contain peptidylarginine deiminase (EC 3.5.3.15), which was indistinguishable from an enzyme preparation from rat muscle in Western immunoblotting and immunoprecipitation. This enzyme was immunocytochemically detected in the cytoplasm but was not secreted into the medium during the cultivation. When the cells were cultured for 2 days with various concentrations of 17 beta-estradiol (E2), the enzyme activity increased in a dose-dependent manner, reaching a maximum level (four- to fivefold higher than control) at about 10(-9) M. This increase in the enzyme activity was evident by 14 hr of culture and became relatively stable after 24 hr. It correlated well with the increase in the amount of the muscle type enzyme per cell as analyzed by Western immunoblotting. Estriol and a synthetic estrogen, diethylstilbestrol, also increased the enzyme activity, whereas testosterone, progesterone, and corticosterone were without effect. An antiestrogen, tamoxifen, which by itself was inactive, partially suppressed the effect of E2. Exposure of MtT/S cells for 14 hr to E2 increased incorporation of 35S-labeled amino acids into the immunoprecipitable peptidylarginine deiminase. This increase was dependent on the concentration of E2, attaining a maximum level (about tenfold higher than the control) at about 10(-9) M. These results indicate that estrogen effects the increase in peptidylarginine deiminase content in the pituitary cells by stimulating enzyme synthesis. PMID- 2246333 TI - Involvement of hexose transport in myogenic differentiation. AB - A high (HAHT) and a low (LAHT) affinity hexose transport system are present in undifferentiated rat L6 myoblasts; however, only the latter can be detected in multinucleated myotubes. This suggests that HAHT is either down-regulated or modified as a result of myogenesis. The present investigation examined the relationship between HAHT and myogenic differentiation. While myogenesis could be inhibited by the potent hexose transport inhibitor phloretin, it was not affected by phlorizin which had no effect on hexose transport. This relationship was further explored using six different HAHT-defective mutants. All six mutants, altered in either the HAHT transport affinity (Type I mutants) or capacity (Type II mutants), were impaired in myogenesis. Since these mutants were selected from both mutagenized and non-mutagenized cells with different reagents, or with different concentrations of the same reagent, the deficiency in myogenesis was likely due to changes in HAHT properties. This notion was confirmed by the observation that growth of Type I mutants in high D-glucose concentrations could rectify the defect in myogenesis. D-glucose was unlikely to rectify the defect in myogenesis, if this defect was due to a second unrelated mutation that may have arisen during isolation of the mutants. Since both types of mutants were not altered in LAHT, D-glucose should still be taken up into the cells. The fact that the glucose-mediated increase in fusion could not be observed in Type II mutants (deficient in the HAHT transporter) suggested that myogenesis was dependent on the presence of D-glucose or its metabolites in specific HAHT-accessible compartments. It is tempting to speculate that trans-acting regulators involved in myogenesis may be synthesized from the glucose metabolites in these specialized HAHT-accessible compartments. PMID- 2246334 TI - Accessory cells induce a polyphosphatidylinositol response when cultured with mitogen-activated T lymphocytes. AB - Monocytes (MO) influenced phosphoinositide metabolism when human T lymphocytes, isolated from peripheral blood, were activated by polyclonal mitogens. In the 3 hr immediately following mitogenic challenge, the synthesis of phosphatidylinositol (PI) was augmented and the synthesis of PI-4-phosphate (PIP) and PI-4,5-bisphosphate (PIP2) was induced in cultures of T lymphocytes and MO. In addition, MO induced a rapid and transient degradation of PIP and PIP2 in T cells prelabeled with [32P]PL and subsequently activated by mitogen. Induction of a PIP/PIP2 response correlated well with induction of DNA replication by MO when T cells were activated by phytohemagglutinin or by neuraminidase plus galactose oxidase. MO did not influence polyphosphoinositide metabolism when T cells were stimulated by the nonmitogenic lectin wheat germ agglutinin. Interleukin 1 could not substitute for monocytes in inducing a polyphosphoinositide response. By causing a rapid and transient release of the second messengers diacylglycerol and inositol phosphates and by subsequently increasing their cellular precursors, MO may induce the interleukin 2 responsive state in T lymphocytes. PMID- 2246335 TI - Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering. AB - Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction, however, is still unknown. Therefore, we have studied the association of mutated EGF receptors with the cytoskeleton. Receptor deletion mutants lacking almost all intracellular amino acid residues displayed no interaction with the cytoskeleton, demonstrating that the cytoplasmic receptor domain is involved in this interaction. Further analysis revealed that receptor-cytoskeleton interaction is independent of receptor kinase activity and the C-terminal 126 amino acid residues, which include the auto phosphorylation sites. Furthermore, it is shown that the high-affinity receptor subclass is not essential for association of low-affinity receptors to the cytoskeleton. EGF receptor-cytoskeleton interaction was increased, however, by treatment with sphingomyelinase, an enzyme known to induce membrane protein clustering, indicating that EGF receptor clustering may cause the association to the cytoskeleton. PMID- 2246336 TI - Annotation: recent life events and psychiatric disorder in school age children. AB - Life events research in school age children using semi-structured interview techniques has only just begun. The advantages, however, for investigating the role of events and difficulties in children's lives outweigh the problems of data collection and training involved in the technique. Improving the collection of information also improves sensitivity at the level of measurement through a consideration of the personal meaning of social experiences. It is already apparent that recent undesirable life events effects of some importance in the genesis of anxious and depressive disorders in school age children. Investigating the social origins of emotional and behavioural disorders, and determining the role of recent social factors in the course and outcome of these conditions, will be substantially advanced by the application of these techniques in future studies. PMID- 2246337 TI - Type of childcare at 18 months--I. Differences in interactional experience. AB - A longitudinal study has followed two-parent families and their first-born child. The families were chosen so that there were three groups of dual-earner families using relatives, childminders and nurseries for day care and one group of single earner families. At 18 mths of age children in the study were observed in the four types of childcare setting. The data from the detailed observations were used to compare the children's interactional experience. The results indicate marked variation in the quality of children's experiences between different childcare settings. Possible reasons for such variation are discussed. PMID- 2246338 TI - Type of childcare at 18 months--II. Relations with cognitive and language development. AB - In a longitudinal study of women and their first-born children the relationship between type of day care experience and cognitive and language development at 18 mths of age was considered. There was a strong association between socio-economic characteristics and type of day care and analyses allowed for this. The results for cognitive development indicate a relationship with mother's education but not with type of day care. For language development the results indicate that children who experience group care were less likely to show much production of different word combinations, but that this was related to the children's language environments. PMID- 2246339 TI - Follow-up of hard-to-manage preschoolers: adjustment at age 9 and predictors of continuing symptoms. AB - Hard-to-manage preschoolers and controls, studied initially at age 3 and followed up at school entry, were followed up again at age 9. Maternal interviews indicated that 67% of the hard-to-manage preschoolers who showed clinically significant problems at age 6 met DSM-III criteria for an externalizing disorder at age 9. Maternal and teacher ratings confirmed the diagnostic data. Hard-to manage youngsters who had improved by age 6 did not differ from comparison children on maternal or teacher reports. Regression analyses indicated that earlier child behavior, maternal behavior, symptom ratings, and ongoing family stress predicted current symptoms of disorder. PMID- 2246340 TI - Preschool behavior problems: stability and factors accounting for change. AB - From a sample of high risk children, groups of acting out, withdrawn, and normal preschool children were identified and followed through first, second, and third grade. A high degree of stability of developmental adaptation was found for each group. Examination of the exceptions to predicted outcomes indicated that discontinuity of development was accounted for by level and change in maternal depressive symptomatology, life circumstances, stressful life events experienced by the family, and quality of the home environment. Level of maternal depression appeared to directly affect the quality of care she provided her child, and indirectly affected the quality and organization of the home environment. PMID- 2246341 TI - Development of infants of drug dependent mothers. AB - Infants of mothers who used methadone, heroin, cocaine and other drugs during pregnancy were compared with a group of control infants over the first 30 mths of life. Results of repeated examinations with the Bayley Scales of Infant Development showed a difference between the groups in mental development. No differences were found in a non-verbal version of the mental scale, but infants of drug dependent mothers seem to have specific difficulties in early language development. In psychomotor development, in behaviour during testing and on a questionnaire on activity, infants of drug dependent mothers did not differ from the comparison children. PMID- 2246342 TI - Autism under age 3 years: a clinical study of 28 cases referred for autistic symptoms in infancy. AB - Twenty-eight children referred with a preliminary diagnosis of autistic disorder under age 3 yrs were extensively examined from the neuropsychiatric point of view and followed up for several months to several years. A diagnosis of autistic disorder was confirmed in 75% of the cases. A variety of associated medical conditions was identified. It was concluded that autism can be diagnosed in a substantial proportion of cases before age 3 yrs and that the neurobiological background is similar to that seen in older autistic children. PMID- 2246343 TI - Major life events and changes in the behavioural functioning of children. AB - The relationship between major life events and changes, across a 2-yr period, in the level of parent-reported behavioural/emotional problems in 1397 children from a general population sample was investigated using a highly modified version of the Coddington Life Events Record and the Achenbach Child Behavior Checklist. The life event questionnaire used in the present study proved to have a satisfactory reliability. The number of life events increased significantly with increasing age of the child, and a higher incidence of such events was found for families with lower socio-economic status. A significant relationship was found between the total score of negative life events across the 2-yr period and changes in the level of behavioural/emotional problems of the children. PMID- 2246344 TI - Mental health and psychosocial functioning in children with recent onset of rheumatic disease. AB - Mental health was evaluated early in the course of juvenile rheumatic disease; 106 parents of children (aged 1-17 yrs) were interviewed and 98 of the children were assessed when the child was hospitalized. Instruments included the Child Assessment Schedule (CAS), the Children's Global Assessment Scale (CGAS) and the Child Behavior Checklist (CBCL). Half the patients received a psychiatric diagnosis; psychosocial dysfunction of at least mild severity was found in 64% of the patients. In the polyarthritic group there was a negative correlation between CGAS and severity of disease. CBCL behaviour scores did not differentiate between patients and siblings when corrected for somatic components. PMID- 2246345 TI - Short communication: the importance of psychosocial factors in understanding child distress during routine X-ray procedures. AB - Thirty-eight children, aged 1-4 years, with a query or definite diagnosis of congenital heart disease (CHD) were observed during an X-ray procedure and their behaviour rated on an amended version of the Observational Scale of Behavioural Distress. Families were followed up and assessed on a number of psychosocial variables. High rates of behavioural distress were found to be associated with children's low stranger sociability and parental style of discipline. Possible patterns of interaction between CHD children and their families are discussed. PMID- 2246346 TI - Assessing the relationship between young siblings: a research note. AB - Methods for assessing the sibling relationship differ markedly, yet these have rarely been compared, or assessed in terms of retest reliability. We report an examination of sibling relationships as assessed by maternal interview, by videotaped observation in structured and semi-structured situations, and by naturalistic observation in unstructured settings. The different approaches to assessment were compared with data on 84 sibling pairs aged between 3 and 10 years. Test-retest reliabilities, assessed on 30 pairs studied on a second occasion, were good for maternal interview information, moderate for videotaped observations, and mixed for naturalistic observations. Independent positive and negative dimensions of the relationship were revealed by each method, and moderate agreement found between methods. Naturalistic observations of 30 minutes' duration were unsuitable for studying the negative aspects of the relationship. PMID- 2246347 TI - Comparison of parent-referred and doctor-referred patients to child psychiatrists in Hong Kong: a research note. AB - The characteristics of 75 children referred to psychiatrists by medical practitioners in Hong Kong were compared with 56 children who were referred by their families to a community clinic. Their demographic characteristics, and the nature and severity of their illness, were quite similar. Medical practitioners tended to refer children with childhood psychosis and psychophysiological disorder. The reasons leading to different types of referral are discussed. A community child mental health clinic may be a useful model for providing psychiatric care to children in Hong Kong. PMID- 2246348 TI - Trace analysis of chloramphenicol residues in egg powders by capillary gas chromatography-electron capture detection. AB - Chloramphenicol (CAP) in egg powder samples was extracted with acetonitrile by sonication. After centrifugation, the supernatant was diluted with water and defatted with n-hexane, and cleanup was performed on a microcolumn of graphitized carbon black (GCB). Different silylation methods were compared for the derivatization of the analytes. Trimethylsilyl N,N-dimethylcarbamate produced stable di-TMS derivatives which were analyzed by capillary gas chromatography electron capture detection (CGC-ECD) after splitless injection. The meta isomer of the chloramphenicol served as the internal standard for quantitation, and 80% + mean recovery was obtained in the 0.1-10 micrograms/kg (ppb) concentration range. PMID- 2246349 TI - A new quantitative thermospray LC-MS method for nicotine and its metabolites in biological fluids. AB - A rapid thermospray liquid chromatography-mass spectrometry (TSP LC-MS) method is described for the simultaneous determination of nicotine and 17 of its metabolites. Chemical ionization of nicotine and its metabolites separated by reversed-phase HPLC is achieved by postcolumn addition of ammonium acetate buffer with the filament of the ion source turned off. Quantification is accomplished by selectively monitoring the unique protonated molecular ion of each metabolite. Trideuterated cotinine serves as an internal standard. Linear responses for cotinine, demethylcotinine, and trans-3'-hydroxycotinine were observed over a concentration range of 20-8000 ng/mL, and 80-8000 ng/ml for nicotine and nicotine 1'-N-oxide. Of the 17 metabolites examined, only nicotine, cotinine, demethylcotinine, and trans-3'-hydroxycotinine were detected in smokers' urine. PMID- 2246351 TI - Determination of cardiac glycosides in digitoxin tablets and deslanoside injections by micro-HPLC. AB - A micro high-performance liquid chromatographic (micro-HPLC) procedure for the assay of digitoxin tablets and deslanoside injections has been developed. Micro HPLC is performed on an ODS micro column, with acetonitrile-methanol-water (10:20:17) for digitoxin tablets and acetonitrile-water (21:70) for deslanoside injections. The effluent is monitored by UV absorption at 220 nm. Quantitation of cardiac glycosides in tablets and injections is carried out by the internal standard method. The composite assay results for digitoxin tablets and deslanoside injections provide average values of 101.2 and 99.9% with standard deviations of 1.2 and 0.93%, respectively. This micro-HPLC method is sensitive, quantitative, and reproducible. It is suitable for use in examining the content uniformity of pharmaceutical preparations. PMID- 2246350 TI - High-performance liquid chromatography for the separation of angiotensin and its metabolites in human plasma and sweat. AB - A reversed-phase high-performance liquid chromatography (HPLC) method with gradient elution for the separation of angiotensin peptides is described. The highly reproducible method allows the base-line separation of angiotensin peptides with UV detection at 225 nm. This chromatographic methodology in combination with radioimmunoassay (RIA) is used for the characterization of angiotensin peptides in human plasma and sweat. PMID- 2246352 TI - Micellar bile salt mobile phases for the liquid chromatographic separation of routine compounds and optical, geometrical, and structural isomers. AB - Aqueous solutions of bile salts, i.e. sodium cholate (NaC), sodium deoxycholate (NaDC), and sodium taurocholate (NaTC), are characterized and evaluated as reversed-phase liquid chromatographic (RPLC) mobile phases. The separation of the ASTM-recommended RPLC test mix in addition to more than 50 other compounds on a C18 column demonstrates the viability of these bile salts as HPLC mobile phases. The Armstrong-Nome theory was applied and found to adequately describe the partitioning behavior of solutes eluted with these bile salts at low surfactant concentrations. The effect of alcohol additives on chromatographic retention and efficiency was also assessed. Not only are the bile salt molecules rigid and chiral, but they form helical micellar aggregates as well. Consequently, many isomeric compounds can be easily resolved with this mobile phase additive. The base-line resolution of some binaphthyl-type enantiomers with a standard C18 column and the bile salt micellar mobile phases is also demonstrated. In addition, these bile salt mobile phases may be preferable to conventional hydroorganic mobile phase systems for the separation of many classes of routine compounds. A brief prospectus on the future utilization of bile salts in liquid chromatography is presented. PMID- 2246353 TI - A rapid and specific high-performance liquid chromatographic assay for theophylline in biological fluids. AB - A rapid, specific high-performance liquid chromatographic analysis of theophylline in plasma, serum, and saliva is described. Proteins present in the biological samples are precipitated with 6% perchloric acid and the clear supernatant is chromatographed on a reversed-phase column. Only 100 microL of serum is required and concentrations as low as 0.07 micrograms/mL can be measured accurately. Other xanthines do not interfere in the assay. Within- and between day variation is less than or equal to 2.2%. The method shows less bias and greater precision than the TDx (Abbott Diagnostics) procedure commonly used in clinical laboratories. PMID- 2246354 TI - Isocratic high-performance liquid chromatographic resolution of glutethimide enantiomers and their 4-hydroxyglutethimide metabolites using cellulose tribenzoate chiral stationary phase. AB - Glutethimide (2-ethyl-2-phenylglutarimide) enantiomers and their corresponding 4 hydroxyglutethimide metabolites (RS and RR) are separated using newly developed commercially available cellulose tris(4-methylphenyl benzoate) ester (Chiralcel OJ) chiral stationary phase and hexane-ethanol or hexane-2-propanol as the mobile phase. The effects of ethanol or 2-propanol concentration in the mobile phase and of column temperature on retention and enantioselectivity of glutethimide enantiomers are also demonstrated. Maximum resolutions of 14.23 and 7.09 are obtained for glutethimide and their 4-hydroxyglutethimide metabolites, respectively, with hexane-ethanol (60:40) at 23 degrees C and a flow rate of 1 mL/min. PMID- 2246356 TI - Liquid chromatographic retention behavior and separation of chlorophenols on a beta-cyclodextrin bonded-phase column, Part II. Monoaromatic chlorophenols: separation. AB - The liquid chromatographic separation of 19 monoaromatic chlorophenols on a beta cyclodextrin bonded-phase column is investigated in both an isocratic and a gradient elution mode. Even though the isocratic mode can be employed for the separation of the member components of each category of chlorophenols (e.g., mono , di-, etc.), significant overlaps between the retention times of the various categories prevent the separation of all chlorophenols on a single chromatogram. Gradient elution can be used, however, for the separation of 15 of the 19 chlorophenol isomers. The unique features of gradient elution as applied to beta cyclodextrin bonded-phase columns are discussed. The detection of chlorophenols with UV and electrochemical methods is also discussed and the two are compared. PMID- 2246357 TI - High-performance liquid chromatographic determination of azaarenes and their metabolites in groundwater affected by creosote wood preservatives. AB - Polynuclear azaheterocyclic compounds (azaarenes) are nitrogen-containing analogs of polycyclic aromatic hydrocarbons (PAHs). The nitrogen atom in the ring system causes these compounds to be slightly polar and considerably more water soluble than related PAHs. A method using a solid-surface sorption technique to extract and concentrate azaarenes and their principle metabolites present in groundwater that contains creosote waste is described. Analyte isolation and concentration is accomplished by solid-phase extraction on n-octadecyl cartridges followed by instrumental determination involving high-performance liquid chromatography. Separations and detection are achieved using flexible-walled, wide-bore columns with ultraviolet and fluorescence photometric detectors connected in series. Fluorescence detection alone is insufficient because the fluorescence response produced by two-ring azaarenes is limited. Short wavelength (229 nm) absorbance detection provides improved sensitivity for these compounds and peak rationing for more definitive identification. In this study, oxygen-containing metabolites of quinoline, isoquinoline, and acridine are detected in groundwater from hazardous waste sites in Pensacola, Florida and St. Louis Park, Minnesota. Concentrations ranging from mg/L to ng/L are measured. The dependence of measured octanol-water partition coefficients on pH is discussed in the context of the isolation chemistry. As a direct bacterial degradation product of acridine with a relatively long environmental persistence, 9-acridinone may serve as a biogenic marker signaling creosote contamination of groundwater. PMID- 2246355 TI - Liquid chromatographic retention behavior and separation of chlorophenols on a beta-cyclodextrin bonded-phase column, Part I. Monoaromatic chlorophenols: retention behavior. AB - The liquid chromatographic retention behavior of nineteen monoaromatic chlorophenols on a beta-cyclodextrin bonded-phase column is investigated with respect to mobile phase composition, pH, temperature, and ionic strength. The mechanistic aspects of retention of these compounds on the beta-cyclodextrin column are studied and compared to other reversed-phase columns. Most of the evidence suggests that the unique selectivity of this column is due to inclusion complex formation, which provides the physical basis for the resolution of positional isomers. Under certain chromatographic conditions, however, the more highly chlorinated congeners appear to be excluded from the cyclodextrin cavity; in such cases a normal-phase chromatographic mechanism is postulated, based on the interaction of the substrates with the secondary hydroxyls on the periphery of the cyclodextrin moieties. PMID- 2246358 TI - Retention behavior of bile acid derivatives using cyclodextrin in the mobile phase in high-performance liquid chromatography. AB - The retention behavior of 3-(1-anthroyl)bile acids together with bile acid glucuronides, sulfates, and 12-dehydro derivatives is examined by the addition of cyclodextrin to the mobile phase in reversed-phase high-performance liquid chromatography. The data suggest that the functional group at the 12 position of the steroid moiety may be the important factor for the formation of the inclusion complex from the solute and cyclodextrin. The separation of these bile acid derivatives is much improved by this inclusion chromatography. PMID- 2246359 TI - Psychological and mood disturbance associated with the diagnosis and treatment of testis cancer and other malignancies. AB - Eighty-seven men with testis cancer (TC) and 35 men with other cancers (OC) completed measures of mood (Profile of Mood States) and of personality and psychopathology (Millon Clinical Multiaxial Inventory). Effects of primary disease, phase of diagnosis and treatment, locoregional vs. cytotoxic treatment, age, and marital status on these measures were examined. TC patients appeared more distressed during treatment, particularly during cytotoxic as compared to locoregional treatment, than before or after treatment, and more distressed than OC patients. Being married appeared to buffer the stress of cancer and its treatment. Although treatment, particularly cytotoxic therapy, appeared to result in transient distress, results did not offer strong evidence that cancer and its treatment typically precipitate severe psychopathology. PMID- 2246360 TI - Coping and attributional styles as predictors of depression. AB - This study examined how coping styles relate to attributional styles and how the two interact in relation to depression. One hundred seventy-six subjects completed the Ways of Coping Checklist, the Attributional Style Questionnaire, and the Beck Depression Inventory. Problem-focused coping correlated with stable and global attributions for positive events for men. Emotion-focused coping correlated with internal, stable, and global attributions for negative events for women and internal and global attributions for men. Correlations between depression and attributions as predicted by the reformulated model of helplessness were significant only for women. These results indicate that research on attributional styles should analyze all data separately by gender. While the results show that both coping and attributions accounted for some of the variance in depression for females, coping contributed considerably more unique variance than attributions. PMID- 2246361 TI - Intense personal experiences: subjective effects, interpretations, and after effects. AB - Following leads by Maslow (1964, 1968) and others who described peak experiences, this study was designed to learn more about the (1) subjective effects; (2) after effects; and (3) interpretations of intense positive and negative experiences. Comparisons were made between respondents' "most positive" and "most negative" experiences and between these positive experiences and those of members of a yoga ashram. It was found that except for the differences in affect, positive and negative experiences were similar in subjective effects and impact on later life. The most positive experience of most respondents fell short of peak experience as described by Maslow. On the other hand, the most positive experience of ashram respondents showed evidence of a genuine alternation of consciousness and lasting life change afterward. The results suggest that only in rare instances is therapeutic change or self-actualization initiated by peak experiences. Implications are discussed. PMID- 2246362 TI - The Jenkins Activity Survey and the CPI-revised: further evidence of adaptive and maladaptive type A traits. AB - This study investigated the relationship with college students (N = 142) between Type A characteristics, as measured by the Jenkins Activity Survey (JAS), and the personality traits measured by the revised California Psychological Inventory (CPI). Significant differences between As and Bs were found on 18 of the 23 CPI traits. Overall, results suggested that the JAS Competitiveness subscale measured adaptive, while the Type A and Speed and Impatience subscales measured maladaptive, characteristics. Furthermore, the thematic deficit associated with the maladaptive Type A characteristics was a lowered sense of integration. Recent explanations of Type A behavior, including those that focus on anger and cognitive appraisals, have not considered this possible lack of integration as a maladaptive aspect of the Type A pattern. PMID- 2246363 TI - Group nightmares about escape from ex-homeland. AB - Escape nightmares (recurrent nightmares about re-escaping ex-homeland) were studied via a 79-item questionnaire administered to 83 Czechoslovak refugees who were living in Switzerland. The key features of the nightmare were not related significantly to the refugees' age, gender, occupation, or educational level. Further analyses dealt with mutual relationships of the various reported aspects of the escape nightmares. The reports of dreaming about arrival in the ex homeland by a "mistake," such as boarding a wrong airplane (i.e., a Freudian parapraxis), were associated with higher levels of (subsequent) dream anxiety, with waking up due to mounting dream tension, and with the dreamer not knowing at first upon awakening whether he was now in the free world or elsewhere. PMID- 2246364 TI - The relationship of demographic variables, antepartum depression, and stress to postpartum depression. AB - This study examined the contributions of demographic variables, antepartum depressive symptoms, and sources of stress to level of postpartum depression. The Beck Depression Inventory (BDI) and demographic data sheet were administered to 69 women during the eighth month of pregnancy. One month after delivery, subjects completed the post-delivery questionnaire and BDI. A stratified hierarchical regression analysis revealed that marital status, antepartum depressive symptoms, and difficulty of pregnancy predicted level of postpartum depression. Somatic stressors of pregnancy may trigger depressive symptoms that persist after childbirth, particularly in unmarried mothers. PMID- 2246365 TI - Stress, coping style, and problem solving ability among eating-disordered inpatients. AB - Stress levels, coping style, and problem solving ability among bulimic and anorexic individuals were explored. Bulimics (n = 33) reported a greater number of negative life events and feelings of being pressured than did a non-eating disordered group. Anorexics (n = 12) reported higher levels of anxiety and depression than the other groups. Both anorexics and bulimics reported higher levels of stress, lower levels of confidence in their ability to solve problems, a tendency to avoid confronting problems, a reluctance to share personal problems, and feelings of being driven. Implications are suggested. PMID- 2246366 TI - What does the Keane et al. PTSD scale for the MMPI measure? AB - The correlations of the Keane, Malloy, and Fairbank (1984) MMPI PTSD scale with DSM-III-based post-traumatic stress disorder symptom, section, and factor score ratings, and with combat history, were studied to determine what aspects of the disturbance it measures (N = 61). The scale's correlations with the various symptom criteria were both substantial and strikingly consistent. However, its relationships with trauma history measures were modest and frequently nonsignificant. The data suggest that the scale is a moderately strong measure of the various PTSD symptoms, but is related only weakly to trauma history. PMID- 2246367 TI - Profile clusters of the MCMI-II personality disorder scales. AB - An analysis was conducted to identify the major personality disorder score profiles to be found in the Millon Clinical Multiaxial Inventory II. Application of Ward's agglomerative hierarchical procedure to two subsamples of psychiatric patients (n = 83 for each) yielded four replicated subgroups. A subsequent K means nonhierarchical approach confirmed four of the Ward clusters. Three subgroups can be characterized as (a) Antisocial, Aggressive (Sadistic), and Passive-Aggressive; (b) Avoidant, Schizoid, and Self-Defeating, and (c) Schizoid, Dependent, and Compulsive. A fourth sizable group is comprised of patients with flat profiles. PMID- 2246369 TI - Concurrent validation of the Levels of Attribution and Change (LAC) Scale. AB - This study examined the temporal reliability and concurrent validity of the LAC Scale, a multidimensional measure of the loci of causal attributions, in a sample of 95 college students. Test-retest coefficients for the 10 subscales averaged .78 for a 2-week interval and .70 for 4 weeks. Six of seven hypotheses related to concurrent validity were supported empirically, including predicted interrelations between the LAC and social desirability, distress severity, psychological-mindedness scores, and the expanded Attributional Style Questionnaire. It is concluded that the LAC Scale is an internally and temporally reliable instrument that possesses concurrent validity and that measures attributional dimensions largely independent of the ASQ. PMID- 2246368 TI - Factor structure of the MCMI among personality disordered outpatients and in other populations. AB - This study examined the factor structure of the Millon Clinical Multiaxial Inventory (MCMI) for a sample (N = 60), which consisted largely of personality disordered outpatients. Results are integrated with previous studies to identify the underlying MCMI dimensions across differing psychiatric populations. Three principal axis Varimax rotated factors emerged from the current study: affectively charged general maladjustment; impulsive acting-out style; and psychotically tinged isolation. Comparison with results of previous studies that involved four diverse samples indicated a large amount of stability for scales that load on the first factor. Factor two shows much less consistency across the five studies, but frequent reappearance of the drug abuse and other acting-out scales suggests a general dimension that reflects acting-out substance abuse. Across studies the third factor shows even more inconsistency, although there is some evidence for a social detachment pattern. PMID- 2246370 TI - Predictors of verbal fluency (FAS) in the healthy elderly. AB - The Verbal Fluency Task (FAS), sensitive indicator of brain injury, was examined in a population of healthy elderly (N = 199, aged 40 to 89 years). The present study was conducted to examine the relative contributions of age, sex, education, verbal intelligence, and specific cognitive abilities to FAS performance. Significant effects were found for vocabulary and sex, although no aging effect was found. Separate norms for sex and level of verbal intelligence are presented. Results indicated that ability to quickly organize information and formulate effective recall strategies played a critical role in good FAS performance. PMID- 2246371 TI - "Practice makes perfect:" retest effects in college athletes. AB - Retest effects on a diverse set of neuropsychological measures were established using a normal sample comprised of college athletes (N = 110). Results suggest that retest effects vary depending on the type of test used, but the magnitude of effect on individual tests can be quite large. Implications of using tests with large retest effects or tests without established retest effect sizes are discussed. PMID- 2246372 TI - Concurrent validity of the Test of Nonverbal Intelligence with referred suburban and Canadian native children. AB - The relationship between the Test of Nonverbal Intelligence (TONI) and the WISC-R was investigated for cultural differences. The samples consisted of 30 suburban and 22 Native children who were referred for learning difficulties. The results indicated the suburban group was higher than the Native group on Verbal IQ, but not Performance IQ, Full Scale IQ, or the TONI Quotient. The correlation coefficient between the TONI Quotient and PIQ was as expected in the Native group, but unexpectedly low in the suburban group. Implications of these findings for the testing of both referred majority and Native group members are discussed. PMID- 2246373 TI - Treatment expectancy as a function of the amount of information presented in therapeutic rationales. AB - This study investigated the effects of content and formal variables in therapeutic rationales on treatment expectancies. Five treatment descriptions were presented to undergraduates (N = 250). The rationales varied in terms of therapeutic focus, number of techniques, and the length of the description. There was no support for the influence of therapeutic focus on expectancies. One of the treatment descriptions raised greater expectancies than the control condition. The effects appeared to be due to the moderate length or amount of information in the rationale. Findings are explained in terms of the perceived clarity of the information and the adequate description of the treatments presented. PMID- 2246374 TI - Client cognitive responses to counselor paradoxical and nonparadoxical directives. AB - Client cognitive responses to counselor paradoxical and nonparadoxical directives were examined. It was predicted (a) that clients who received paradoxical symptom prescriptions would display a greater negativity toward the counselor and counseling than those who received nonparadoxical directives; and (b) that clients who received no rationale for the paradoxical directives would display a greater negativity than those who received a rationale. Thirty clients who had reported performance anxiety received one 45-minute counseling interview. Ten clients received paradoxical directives with a rationale, 10 received paradoxical directives with no rationale, and 10 received nonparadoxical directives. Results showed no significant differences in either client in-session negativity or out of-session implementation of directives between the paradoxical and nonparadoxical conditions and between the rationale and no rationale paradoxical conditions. Possible implications of the findings are discussed. PMID- 2246375 TI - Effects of two self-control procedures on modifying Type A behavior. AB - Two groups of Type A subjects who received either anxiety management training focused on coping with anger and hostility or operant self-control procedures were compared with a control group. Treated subjects compared to controls showed significant reductions in the overall Type A behavior, hard-driving/competitive, and speed/impatience scores. The results supported the hypothesis that both self control training methods provide the opportunity to adapt more effective coping strategies and to rely less on Type A coping techniques. Self-control procedures such as anxiety management training and operant self-control are promising methods for reducing Type A behaviors even in the Japanese culture. Implications of selecting the most effective treatment for each CHD-pathogenic behavior are discussed. PMID- 2246376 TI - Change in patient affect/defense ratio from early to late sessions in brief psychotherapy. AB - The current study examined changes in the ratio of patients' affective and defensive behaviors during the course of brief psychodynamic psychotherapy. Treatments of 16 patients were videotaped. For each patient, four sessions were evaluated with a minute-by-minute coding system of process variables. When patients were grouped according to outcome scores, significant differences between the high outcome and the average-to-low outcome groups emerged. During the early phase of treatment, patients in both groups showed an average of one affective response per five defensive responses. By the late phase of treatment, the high outcome patients showed a marked shift to one affective response per two defensive responses, while the low outcome patients remained the same. An incidental finding was a negative correlation between good outcome and the ratio of defensive behavior to total patient activity. PMID- 2246377 TI - Defense mechanisms in clients and non-clients as mediated by gender and sex-role. AB - This study examined defense mechanism utilization patterns of psychotherapy clients vs. individuals without mental health history, by administering the Defense Mechanism Inventory to 104 subjects. Concurrently, the mediating influence of gender and sex-role on defense mechanism utilization was assessed. Results indicated that gender and sex-role were significant in mediating the use of Turning against Self defenses and Turning against Other defenses, respectively. More importantly, however, psychotherapy clients differed from non clients in their increased use of Projection and their decreased use of Principalization. Use of Projection was mediated further by a gender by sex-role interaction, which complicates the interpretation of the presence of Projection in an individual for the clinician. PMID- 2246378 TI - Further exploration of the Egocentricity Index in an inpatient psychiatric population. AB - Using the Rorschach protocols from 129 adult psychiatric inpatients, the Egocentricity Index as calculated in the Exner Comprehensive System was investigated relative to MMPI standard and special scales, Beck Depression Inventory, and other Rorschach variables. Results indicate that rather than being a measure of self-focus and self-centeredness, the Index might be related to introversion and introspection. Additionally, the Index may have differential implications about mental health for males vs. females. PMID- 2246379 TI - The relationship between a diagnosis of antisocial personality and hostility: development of an Antisocial Hostility scale. AB - An antisocial hostility scale was developed by correlating items of the Buss Durkee Hostility Inventory with a diagnosis of antisocial personality (ASP) as determined by a computerized version of the DSM-III. Fifty-two male volunteers for drug-related studies at the Addiction Research Center were used for a preliminary test development sample. The scale developed thereby was related significantly to a diagnosis of antisocial personality in a cross-validation sample of 28 drug abusers. A final scale was developed by obtaining correlations between ASP and Buss-Durkee items using the subjects from both of these preliminary samples. Items that comprise the scale were predominantly behaviorally oriented hostility items covered by the Assault scale rather than affective items such as those in the Resentment scale. In a 122 cross-validation sample the scale was related significantly to a diagnosis of antisocial personality. The study confirms the generality of the criterion of overt aggression as a condition for meeting DSM-III criteria for antisocial personality. PMID- 2246380 TI - Tavern patrons and the MacAndrew Alcoholism Scale: self-reported drinking behavior in relation to the MMPI L and K scales. AB - This study investigated the ability of the MacAndrew Alcoholism (MAC) Scale to distinguish between alcoholics and nonalcoholics using self-ratings from patrons of taverns (N = 128); while only about 14% of the variance in the MAC Scale was accounted for by the self-rating (alcoholic/nonalcoholic) scale, the MAC Scale correctly identified 70% of those who reported alcohol use to levels consistent with alcoholic dependency after variance in the alcohol use scale attributable to the L and K scales of the MMPI was accounted for. PMID- 2246381 TI - A semantic analysis of the various ways that the terms "affect," "emotion," and "mood" are used. AB - A survey of authoritative psychiatric texts reveals that the terms "affect," "emotion," and "mood" are employed inconsistently. The authors consider some of the meanings these terms have and suggest that feeling states be defined in terms of their duration, whether they are subjective and/or objective, the role of cognition, and the phenomenological level. The study of the patient's facial expression and vocal acoustics offers empirical support for these distinctions. For example, flat affect can be differentiated from depression, and inappropriate affect appears not related to affects, but rather emotions. It then becomes possible to examine clinically important interactions among these processes. PMID- 2246382 TI - Parameters of emotional processing in neuropsychiatric disorders: conceptual issues and a battery of tests. AB - Components of emotional processing were examined in psychiatric and neurological populations: communication channel (face/voice), processing mode (expression/perception), and emotional valence (positive/negative). These were assessed with an experimental affect battery which was administered to schizophrenic, unipolar depressive, right-brain-damaged, Parkinson's disease, and normal control right-handed adults. For expression, subjects were taped while producing facial and vocal emotional expressions. Judges rated the expressions for accuracy and intensity. For perception, subjects were asked to identify and discriminate facial and vocal emotions. Using correlational techniques, relationships between facial and vocal channels and between expressive and perceptual modes were explored. The test battery has good psychometric properties and discriminates among diagnostic groups. PMID- 2246383 TI - Neurobiological and cultural aspects of facial asymmetry. AB - Facial asymmetry refers to the fact that the left and the right sides of the face during movement or rest are not identical. This asymmetry can be produced by a range of factors, such as ones that are anatomical, physiological, neurological, psychological, pathological, or sociocultural. Interaction among these various factors is not uncommon and has the potential to confound scientific investigations. When focusing on asymmetrical facial movements and expressions- which is the issue of this article--one has to make sure to control for other types of asymmetries that could confound the observations. To ensure such control, adequate judgment and measurement techniques are necessary. Some of these techniques are briefly described in this article. Furthermore, some explanations for facial asymmetrical movements are considered. From a neuropsychological perspective, it is suggested that asymmetrical facial expressions have some relationship to the functional asymmetry of the brain. But social-psychological and cultural factors, it is argued here, may also play an important role in the phenomenon of asymmetrical facial expressions, although no definitive statements regarding the nature of their role are made at this point. PMID- 2246384 TI - Spontaneous expression of facial emotion in schizophrenic and right-brain-damaged patients. AB - The primary neuropsychological theories of schizophrenia have emphasized disturbed dominant hemisphere functioning, although schizophrenics (SZs), particularly those with flat affect, may have deficits resembling those of patients with damage to their right hemisphere. SZs, right-brain-damaged patients (RBDs), and normal controls (NCs) were videotaped while talking about a pleasant and an unpleasant experience. Raters viewed the video recordings of facial activity with the audio portion turned off and assessed the intensity of emotion, the amount of positive emotion, and the amount of negative emotion. Compared to controls, both patient groups were judged as less expressive and as displaying more negative than positive emotion. In particular, the patients seemed to have difficulty with the expression of positive feelings. For the SZ group, these findings may be related to anhedonia or to poor social functioning, which are often features of the illness. The findings for the RBD group are contrary to previous studies which have suggested that the right hemisphere is specialized for negative emotion. PMID- 2246385 TI - Effect of inversion on memory for faces in Parkinson's disease and right hemisphere stroke patients. AB - Upright and upside-down photographs of faces, schematic drawings of faces, and photographs of houses were presented to patients with Parkinson's disease (PD), patients with right hemisphere stroke (RH), and age-matched normal control subjects (NC) in a forced-choice recognition paradigm. These slides were presented in four orientation conditions: upright at original presentation and at test, upside-down at both, upright initially and upside-down at test, and vice versa. NC subjects recognized faces most accurately when presented in the same orientation both times. This suggests that the information is resistant to mental rotation. Patients with PD recognized faces most accurately when they were presented upright both times, suggesting difficulty with any unusual orientation, consistent with an inability to shift mental set. RH patients, unlike the other groups, did not recognize faces presented upright both times more accurately than those in any other condition. This supports previous studies suggesting a right hemisphere specialization for recognition of upright faces. PMID- 2246386 TI - The components and neuroanatomic bases of prosody. AB - Following a discussion of the various aspects and types of prosody, the literature relevant to its neuroanatomy and neuropsychology in normal, brain injured, and psychiatric populations is reviewed. Evidence linking neurophysiologic mechanisms with components of prosody is presented. PMID- 2246387 TI - Interpersonal communication in the context of dementia. AB - The assessment of dementia draws, primarily, on measures of memory and language. However, dementia also affects interpersonal and social functioning. Therefore, objective assessment of interpersonal interaction may provide relevant and sensitive measures of the severity and type of dementia. We examined the vocal acoustics and interpersonal interactions of a group of patients with Parkinson's disease and mild to moderate dementia. Objective measures of performance during a semistructured interview correlated with clinical ratings made independently by a neurologist. Our findings indicate that dementia affects interpersonal abilities in specific ways that can be objectively measured using computer analyses of speech patterns. PMID- 2246388 TI - An automated system for the analyses of temporal speech patterns: description of the hardware and software. AB - A system (WELMAR II) is described for analyzing time patterns of speech on small computers. Temporal speech patterning refers to the pacing of the sounds and silences that make up a stream of speech. The system is particularly useful for research involving clinical populations since it has been shown that speech rhythms are sensitive to interpersonal influence, to dimensions of personality, and to psychological pathology. PMID- 2246389 TI - Spontaneous proliferations in Australian marsupials--a survey and review. 1. Macropods, koalas, wombats, possums and gliders. AB - This report catalogues all spontaneous proliferations in macropods, koalas, wombats, and possums and gliders held by the Comparative Pathology Registry at Taronga Zoo. Proliferative lesions were present in 14 macropods, 26 koalas, two wombats and 22 possums and gliders. Most neoplasms recorded in macropods were singular and many were found incidentally. Lymphoid neoplasia, cranio-facial tumours and apparent mesotheliomas were common in koalas. Hyperplastic or benign neoplastic masses in adrenals and livers were common in possums. In addition, previously misdiagnosed splenic haematopoietic hyperplasia was common in these animals. Mammary proliferations were present in macropods and gliders. No obvious aetiological factors have been identified in any of the tumour conditions, although there is some evidence to suggest a viral involvement in lymphosarcoma in koalas. PMID- 2246390 TI - Spontaneous proliferations in Australian marsupials--a survey and review. 2. Dasyurids and bandicoots. AB - This report catalogues all spontaneous proliferations in dasyurids and bandicoots held by the Comparative Pathology Registry at Taronga Zoo. Proliferative lesions were present in 70 dasyurids and three bandicoots. Hyperplastic or benign neoplastic masses in adrenals and livers were common in dasyurids. In addition, previously misdiagnosed splenic haematopoietic hyperplasia was common. A variety of mammary proliferations was present in dasyurids. Dasyurids often had multiple proliferative lesions. Lymphoid neoplasia was common, especially in the smaller dasyurids. No obvious aetiological factors have been identified in any of the tumour conditions in dasyurids although there is some evidence to suggest a genetic predisposition to lymphosarcoma in the fat-tailed antechinus. PMID- 2246391 TI - Lesions of toxoplasmosis in Australian marsupials. AB - This report describes toxoplasmosis lesions in Australian marsupials. Clinical signs, necropsy findings and histopathological changes are summarized for 43 macropods, two common wombats, two koalas, six possums, 15 dasyurids, two numbats, eight bandicoots and one bilby. Animals either died suddenly without clinical signs or exhibited signs associated with respiratory, neurological or enteric disease. At necropsy, many marsupials had no visible lesions. Where present, common necropsy findings included pulmonary congestion, oedema and consolidation, adrenal enlargement and reddening, haemorrhage and ulceration of stomach and small intestine, and lymphadenomegaly and splenomegaly. Microscopically, affected lungs showed interstitial pneumonia and macrophage accumulation. Myocardial, skeletal and smooth muscle necrosis and neutrophilic inflammation were common. Organs had focal necrosis and/or fibrosis and lymphoid infiltrates. Toxoplasma gondii tissue cysts were common in muscle and nervous tissue. Free tachyzoites were commonly present in areas of necrosis. Selected sections from four macropods, two koalas, two dasyurids, one wombat and one possum stained specifically with avidin-biotin complex and anti-Toxoplasma gondii serum. PMID- 2246392 TI - Myopathy in cattle induced by alkaloid extracts from Thermopsis montanta, Laburnum anagyroides and a Lupinus sp. AB - A purified alkaloid preparation containing N-methylcytisine, cytisine, 5,6 dehydrolupanine, thermopsine and anagyrine from Thermopsis montana induced prolonged recumbency and microscopic acute hyaline skeletal myodegeneration with myofibre regeneration in cattle similar in type and severity to that induced by Thermopsis montanta plant material. This indicates that the alkaloid(s) of Thermopsis montana are responsible for the myopathy caused by the plant. An alkaloid preparation containing mostly anagyrine from a Lupinus sp. and an alkaloid preparation containing only cytisine from Laburnum anagyroides each caused microscopic skeletal muscle degeneration and necrosis similar to, but less severe than, the alkaloid extract from T. montana, but without clinical recumbency. Dosage and severity of response suggest that neither of those two alkaloids alone can account for the effects induced by Thermopsis. The data suggest that quinolizidine alkaloids with a alpha-pyridone A-ring may be responsible for the lesions and that individual alpha-pyridones may have additive effects. PMID- 2246393 TI - In vitro replication of Bovid herpesvirus-1 in macrophages derived from peripheral blood leucocytes of calves. AB - Macrophages derived from peripheral blood leucocytes of calves from 1 to 100 days of age supported the replication of Bovid herpesvirus-1 (BHV-1) without apparent cytopathic effects. The replication of the virus was abortive, replication being restricted to limited numbers of passages. The abilities of macrophages to support replication of BHV-1 were similar for calves from 1 day to 100 days of age (P greater than 0.05). The replication of BHV-1 in macrophages did not significantly affect the capacity of macrophages to phagocytose and kill Staphylococcus aureus (P greater than 0.05). PMID- 2246394 TI - Non-effect of regional lymph node removal on growth of ovine aural squamous cell carcinoma. AB - The effect of ipsilateral parotid lymphadenectomy on growth of lesions of aural squamous cell carcinoma in 10 adult ewes was compared over a 6-month period, with matched, tumour-affected controls that were not subjected to parotid lymphadenectomy. There was no significant difference between groups, indicating that the regional lymph node had no influence on the growth of the tumour. PMID- 2246395 TI - Larval parasites in lymph nodes of slaughter cattle. AB - Between 1977 and 1989, evidence of parasitic infection was found in lymph node sections of twelve cattle (0.5 per cent of lymph nodes) submitted by Canadian federal meat inspectors under the tuberculosis eradication program. Macroscopically, all lesions were green foci of various sizes; microscopically, parasitic larvae were surrounded by a wide zone of eosinophils. Nine larval parasites were identified in mesenteric and one parasite in an unidentified lymph node(s). Although rare, such lesions must be defined in order to differentiate them from other aetiologies such as mycobacterial and sarcocystic granulomas. PMID- 2246396 TI - Further studies on the regulation of the Harderian glands of golden hamsters by the thyroid gland. AB - Long-term increased or decreased circulating levels of thyroid hormones significantly modify porphyrin concentrations and morphology in the Harderian glands of male and female hamsters. Administration of T3 reduced porphyrin concentrations in females; this treatment or decreasing thyroid hormone levels with KClO4 suppressed the post-castration rise of porphyrins in males. Hypophysectomy led to increased porphyrins in the Harderian glands of males; this rise was suppressed in hypophysectomized males by T3 or T4. In females, hypophysectomy reduced porphyrins which were further reduced by daily administration of T3 or T4. These modifications in the normal females were identical in castrated males. Mitotic activity in the Harderian glands of females was stimulated by KClO4 and by hypophysectomy with or without exogenous T3. In males, castration increased mitotic activity which was suppressed by T3 and exacerbated by KClO4. Increased mitotic activity seemingly follows loss of tissue mass. The data show that thyroid hormones act directly on the Harderian glands rather than indirectly through modification of TSH synthesis/release. Female "type" glands in males are a consequence of loss of gonadal androgens by castration, or by suppression or loss of thyroid hormones by hypophysectomy or by treatment with KClO4. However, male "type" glands in females are the result of androgen treatment, and/or increased levels of thyroid hormones via reduced ambient temperatures or of photic input. We conclude that regulation of the Harderian gland appears to be different in the two sexes. PMID- 2246397 TI - Errors in federal report on dental health personnel present problems. PMID- 2246398 TI - Comparing learning logs and note summaries in a dental research methods course. AB - This paper reports a study that examines how two types of writing influenced dental students' performance in critical thinking and recall in a graduate research methods course. Forty-five students in this five-week, lecture-based course were stratified by dental specialty and randomly assigned to one of two groups. The treatment group kept learning logs, expressing personal understanding of lecture material; a second group wrote note summaries, entailing the reorganization of key lecture points. Each student was asked to write for a ten minute interval during each class meeting. Mean scores for the log writers were higher on a post-course essay measure of critical analysis; note summarizers performed better on recall; while in the direction predicted, differences did not reach statistical significance. Note summarizers' attitude toward future use of their activity in other classrooms was more positive and they complied more highly with their activity than did the log writers. This preference for the note summary method suggests that students may find the structured nature of the summary more useful when being introduced to a dental concept. PMID- 2246399 TI - Tobacco use cessation curricula in the U.S. dental schools and dental hygiene programs. AB - Tobacco-related health problems are the most preventable forms of illness in the United States. By assuming proactive tobacco use cessation counseling roles, dentists and dental hygienists can help reduce the number of people who currently use tobacco. The literature reports that many oral health professionals feel unprepared to assume such roles. To help combat the problem of tobacco-related illness and to help prepare dentists and dental hygienists to assume tobacco use cessation counseling roles, dental schools and dental hygiene programs need to develop appropriate didactic and clinical tobacco use cessation curriculum content. To date, there are limited national data addressing the extent of tobacco use cessation education in dental schools and dental hygiene programs. Studies of medical schools have revealed a need for increased curriculum content on tobacco use prevention and cessation. Further, tobacco use cessation training programs for medical students, practicing dentists, and dental hygienists have resulted in increased student and provider confidence when tobacco use cessation counseling roles were assumed. This study surveyed all dental schools and dental hygiene programs in the U.S. to determine if tobacco-related curriculum content exists, and if so, to what extent. Variables addressed included allocated hours, subject content, scope, department responsible, workplace smoking policy, importance, and future curricular directions. Questionnaires were mailed to all dental hygiene program directors and dental school academic deans. Study findings suggest that dental and dental hygiene students receive limited tobacco use cessation education, and respondent schools have no immediate plans for curriculum change in this area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246400 TI - Dental school-based continuing education in tobacco use cessation counseling for oral health care providers. AB - The role of health care providers in patient counseling for tobacco use cessation has gained increased attention in recent years. The present survey examined the activities of dental school continuing education departments in providing continuing education in tobacco use cessation counseling to oral health care personnel. A questionnaire was sent to the director of continuing education at all U.S. and Canadian dental schools. The results indicate that few continuing education programs have been or currently are being offered. Respondents to the survey perceived little interest in this topic among their target audiences. The reasons for the current situation and barriers to practitioner involvement are discussed. PMID- 2246402 TI - Evaluation of orthodontic education by recent graduates. PMID- 2246401 TI - Teaching recognition skills to improve products. AB - All 86 first year dental students in a Conservative Restorations course completed five sets of instructional tasks. Tasks followed a discrimination learning paradigm, a sequence based on the principal that recognition skills are a prerequisite for production skills. Recognition skill measures and production quality measures were collected for pre- and post-test Class 1 amalgam preparations. Significant improvement was found in three of the five recognition skill measures and in quality of production. Stepwise multiple regression analysis showed that a measure of student agreement with faculty evaluations accounted for 46.3 percent of the variance in post-test production scores whereas traditional admissions measures accounted for less than 4 percent of the variance. Additionally, students who improved recognition skill showed a corresponding improvement in products. The paradigmatic teaching model appears to be valid for Class 1 cavity preparations. PMID- 2246403 TI - An update on academic dismissal for clinical reasons. PMID- 2246404 TI - Embryologic fusion planes and the spread of cutaneous carcinoma: a review and reassessment. AB - It has long been held that embryologic fusion planes influence the spread of skin cancer. Embryologic fusion planes have been implicated in the depth of invasion, horizontal spread, and recurrence of cutaneous carcinoma. However, these structures have never been studied in detail. A review of the surgical literature reveals considerable confusion regarding the exact nature, location, and tumor interactions of these fusion planes. We review the gross and microscopic development of sites of embryologic fusion. We examine histologic sections through fusion sites in normally developed adult and fetal fresh cadaver specimens. Our studies, supported by our review of developmental anatomy, indicate that fusion planes do not persist as identifiable anatomic structures that would influence tumor spread. PMID- 2246405 TI - Effect of the topical anesthetic EMLA on the efficacy of pulsed dye laser treatment of port-wine stains. AB - EMLA cream (Eutectic Mixture of Local Anesthetics) is a new topical anesthetic composed of 25 mg lidocaine and 25 mg prilocaine in an oil-in-water emulsion cream. It has been found to be very effective for local anesthesia prior to venepuncture, minor surgical procedures, and pulsed dye laser (PDL) therapy for port-wine stains (PWS) in children. However, since EMLA may cause vasoconstriction of cutaneous vessels, we tried to determine whether pretreatment with EMLA decreases the efficacy of subsequent PDL treatment. We report eight patients between the ages of 4 and 32 years with PWS who received two test site treatments prior to PDL treatment. One site was pretreated with EMLA cream under occlusion for 60 minutes and then left unoccluded for 15 minutes prior to PDL test treatment. The other site, in the same area of the PWS and patient's body, was not pretreated with EMLA. The test sites were compared 6-8 weeks later to determine whether EMLA decreased the degree of lightening of the PWS compared to the non-EMLA-treated site. We conclude that EMLA is an effective topical anesthetic for PDL treatment of PWS and does not adversely affect the efficacy of the treatment. PMID- 2246407 TI - Hydroquinone-induced localized exogenous ochronosis treated with dermabrasion and CO2 laser. AB - Exogenous localized ochronosis can result from the repeated use of hydroquinone containing creams, many of which are available over the counter. We report a case that was managed by dermabrasion and CO2 laser. The incidence and proposed etiologies of hydroquinone-induced exogenous ochronosis are reviewed. PMID- 2246406 TI - Use of Mohs micrographic surgery to establish quantitative proof of heightened tumor spread in basal cell carcinoma recurrent following radiotherapy. AB - We compared 27 basal-cell carcinomas (BCCs) recurrent following radiotherapy and subsequently excised by Mohs micrographic surgery to a control group of BCCs recurrent following other treatment modalities and similarly excised. Mohs technique permitted precise, quantitative tumor assessment, obtained via a novel method utilizing three parameters: the number of surgical stages required for complete excision, the percentage increase between clinical preoperative tumor area and final postoperative defect area, and the presence of deep subcutaneous tissue invasion. Figures for the postradiation group were larger in all three categories, with the latter two revealing statistically significant differences versus the nonradiation group. This study gives strong, direct quantitative support to the clinical impression that BCC recurrent following radiotherapy is a uniquely aggressive, invasive subset of recurrent BCC. PMID- 2246408 TI - Congenital midline nasal masses: diagnosis and management. AB - Congenital midline nasal masses (CMNMs) are rare lesions most commonly caused by dermoids, hemangiomas, nasal gliomas or encephaloceles. We report a case of nasal glioma and discuss the embryologic development, evaluation, and management of such CMNMs. PMID- 2246409 TI - Complete spontaneous regression of multiple basal cell carcinomas in the basal cell nevus syndrome: the possible role of transepithelial elimination. AB - A 36-year-old Latin American man with the basal cell nevus syndrome had multiple, soft, hairless, depressed scars of the face, scalp, neck, and back, ranging in size from 0.3 x 0.5 cm to 3.5 x 3.9 cm. These areas had never been treated and previously were sites of basal cell carcinomas that underwent complete spontaneous regression 4-5 years from the date of onset. Pathology of these spontaneously regressed sites was consistent with the criteria established by Curson and Weedon (1979). Type III transepithelial elimination was demonstrated for a basal cell carcinoma. Type III transepithelial elimination may play a role in the spontaneous regression of basal cell carcinomas. PMID- 2246410 TI - New primary basal cell carcinomas arising in skin flaps following Mohs micrographic surgery for primary and recurrent basal cell carcinoma. AB - Two patients developed new primary basal cell carcinomas (BCCs) in skin flaps used to reconstruct wounds that followed an earlier primary BCC and a recurrent BCC treated by Mohs micrographic surgery. Criteria for distinguishing a new primary BCC arising in a skin flap or full-thickness skin graft at a previous treatment site for BCC from a truly recurrent BCC are presented. The distinction between a new primary BCC and true tumor recurrence is important for accurate clinical assessment and may have a dramatic impact on the type of subsequent treatment. In addition, there may be less medicolegal liability in the case of a new primary BCC arising at the site of a previously treated BCC than for a BCC that is determined to be recurrent. PMID- 2246411 TI - The history and contributions of the Spanish dermatosurgical school. AB - The origin of dermatologic surgery in Spain may be traced to the efforts of Professor Felipe de Dulanto, Initially the specialty encompassed only simple direct closure, local flaps, and skin grafts. As the field evolved, distant flaps and other techniques, including dermabrasion, cryosurgery, Mohs' surgery, and laser surgery, were added to the armamentarium. The close, interdepartmental relationships between Dermatology and Otolaryngology, Ophthalmology, Pediatrics, and Gynecology allowed Spanish dermatologic surgery to expand and encompass lymph node dissections, complex reconstructions of the neck, eyelid, vulvar area, breasts, and abdomen. PMID- 2246412 TI - The history of the American Society for Dermatologic Surgery and its impact on the specialty of dermatology. PMID- 2246413 TI - Make your incision where you want your final scar line to be: A surgical philosophy. PMID- 2246414 TI - A patient with transient hypertension and visual disturbance following the use of scleremo. PMID- 2246415 TI - Target blood gases during ARDS ventilatory management. PMID- 2246416 TI - Current therapeutic strategies in severe acute pancreatitis. PMID- 2246417 TI - The use of radionuclide techniques in the assessment of alveolar-capillary membrane permeability on the intensive care unit. PMID- 2246419 TI - Early prediction of prognosis in out-of-hospital cardiac arrest. AB - Of 347 victims of out-of-hospital cardiac arrest 196 (56.5%) died before and 109 (31.4%) after admission to hospital, while 42 patients (12.1%) were discharged alive. The 37 patients (10.7%) discharged without severe hypoxic brain damage were assigned to the group with "good", the remaining 310 patients to the group with "poor outcome". From results of stepwise logistic regression, a score was derived to specifically identify victims with poor prognosis (values in brackets = score points; cutpoint: score greater than 3 points): age less than or equal to 70 (0), 71-80 (1), greater than 80 (2); ECG ventricular fibrillation (0), other (1); no aspiration (0), aspiration (1); pupils round (0), not round (1); gasping (0), apnea (1); bystander resuscitation--yes (0), no (1). Evaluation of the score revealed a specificity of 100% (0.95 confidence interval: 80%-100%) and predictive value of 100% (0.95 confidence interval: 95%-100%). A predictive score for specific identification of victims with poor prognosis can contribute to decision making in out-of-hospital cardiac arrest. PMID- 2246418 TI - Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. AB - Many animal studies have shown that high peak inspiratory pressures (PIP) during mechanical ventilation can induce acute lung injury with hyaline membranes. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a "lung injury score" greater than or equal to 2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%, chi 2 = 11.64, p less than 0.001). Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure. PMID- 2246420 TI - Errors in tracheal pressure recording in patients with a tracheostomy tube--a model study. AB - The recording of intratracheal pressure in patients breathing through a tracheostomy tube is marred by methodological problems. In model experiments it has been shown that the introduction of a recording catheter into the tracheostomy tube alters the recorded pressure by as much as 20-40%. To avoid such inaccuracy, a specially designed tracheostomy tube is proposed with an externally placed channel for introduction of the recording catheter. In in vivo measurements, recordings can be made at a distance of up to about 20 mm below the end of tube. Pressure recordings from this part of a model trachea are compared with results obtained from a reference pressure port 100 mm below the tube ending. The results show that it is possible to record expiratory pressure with good accuracy but that inspiratory pressure is still overestimated by 9-16%. PMID- 2246421 TI - Nosocomial maxillary sinusitis during mechanical ventilation: a prospective comparison of orotracheal versus the nasotracheal route for intubation. AB - Nosocomial maxillary sinusitis during mechanical ventilation may cause life threatening complications in ICU patients. The aim of this prospective study was to compare the incidence of maxillary sinusitis according to the route of intubation. 111 consecutive adult patients (mean age: 53, mean SAPS: 12) were randomly assigned to receive either orotracheal (n = 53) or nasotracheal (n = 58) intubation. All had a nasogastric feeding tube. Patients with head trauma or mechanical ventilation for less than 48 h were excluded. Sinusitis diagnosis was made by radiography (waters' view) at the bedside. The two groups were similar in age, SAPS, duration of ventilation. Maxillary sinusitis occurred in 1/53 (1.8%) of the orotracheal group (on the nasogastric tube side), and in 25/58 (43.1%) of the nasotracheal group (7 on the nasogastric tube side, 11 on the endotracheal tube side, 7 bilateral; p less than 0.001). Nine of the 26 cases of sinusitis were initially treated by sinus drainage because of signs of infection (3 failures) and the 17 others were treated by tube removal. This procedure proved successful in 12 out of 17 cases but secondary drainage was performed in 5 cases (1 failure). Incidents related to the route for long-term intubation were significantly (p less than 0.001) more frequent in the orotracheal group (8/53 vs 2/58), however no patient died because of them. In this study, long-term orotracheal intubation reduced significantly the incidence of maxillary sinusitis in comparison with nasotracheal intubation. PMID- 2246422 TI - Theophylline poisoning--a review of 64 cases. AB - Sixty-four cases of theophylline poisoning were reviewed. All but two cases represented international self poisoning. The majority of patients were young females who presented acutely after ingestion of sustained release preparations prescribed for asthma. Serum theophylline levels (mean 365 mumol/l, SD 177) indicated a high risk of toxicity. Electrolyte and metabolic abnormalities (hypokalaemia, hypomagnesaemia, hypophosphataemia, hyperglycaemia, acid-base disturbances and leucocytosis) were common. Serum potassium, serum glucose, leucocyte count and length of stay in the intensive care unit all correlated strongly with maximum serum theophylline level (p less than 0.001). The low incidence of life-threatening manifestations of severe toxicity (hypotension, serious arrhythmias or seizures) and excellent outcome, contrasts with many previous reports. The results support the use of a management regimen which emphasizes intensive supportive therapy and restricts the use of charcoal haemoperfusion. PMID- 2246423 TI - Effects of thiopental on resistance vessels in cat skeletal muscle. AB - Barbiturates are used clinically as anaesthetics and to reduce raised intracranial pressure. One side effect is hypotension, usually ascribed to a depression of cardiac contractility, while their effects on the resistance vessels are more controversial: both vasodilation and vasoconstriction have been described. This study analyzes the effects of thiopental on basal vascular tone in the cat skeletal muscle. We found that total resistance increased by almost 20% at low (50 mumol/l) and decreased down to about 50% of control at high (350 mumol/l) plasma concentrations of thiopental. The vasoconstriction dominated in the large arterioles (i.d. greater than 25 microns) and the vasodilation in the small arterioles (i.d. less than 25 microns). A dose-dependent inhibition of myogenic vascular reactivity (here defined as the maximum resistance increase to a transient rise in transmural pressure) coincided with the vasodilation. Autoregulation of blood flow was depressed by thiopental. During vasoconstriction there was a net transcapillary fluid absorption and during vasodilation a net fluid filtration. The fluid movements could be ascribed to variations in capillary hydrostatic pressure. If applicable to the cerebral circulation these results suggest that thiopental at high plasma concentrations might induce, instead of reduce, interstitial brain oedema. PMID- 2246424 TI - Pulmonary embolism in end stage renal disease. AB - Clinically significant pulmonary embolism is considered to be rare in patients with end stage renal disease. Two cases with long standing renal disease on dialysis, are reported where pulmonary embolism contributed significantly to morbidity and mortality. One patient had hypotension during dialysis. The differential diagnosis of sustained hypotension during dialysis or in the ICU should include pulmonary embolism. Establishing the diagnosis may require pulmonary angiography. PMID- 2246425 TI - Postoperative respiratory failure due to acute eosinophilic pneumonia. AB - A non-smoking 63-year-old man developed respiratory failure following surgical repair of a thoracoabdominal aortic aneurysm. He had severe hypoxemia and an elevated minute ventilation requiring prolonged mechanical support. Initial postoperative chest radiographs revealed new, transient, migratory infiltrates, and the patient received broad-spectrum antibiotic therapy. Chest radiographs subsequently demonstrated persistent, diffuse infiltrates, and bronchoalveolar lavage (BAL) analysis demonstrated significant eosinophilia (30%) with no evidence of infection. A diagnosis of acute eosinophilic pneumonia was made, and treatment with intravenous methylprednisolone resulted in rapid clinical improvement, and extubation. Acute eosinophilic pneumonia is not a previously recognized cause of postoperative respiratory failure and prolonged mechanical ventilation. It should be suspected in postoperative patients with unexplained diffuse lung infiltrates and acute respiratory failure. PMID- 2246426 TI - Severe rhabdomyolysis related to heroin sniffing. PMID- 2246427 TI - Hobgoblins. PMID- 2246428 TI - Attributions for social failure and aggression in incarcerated delinquent youth. AB - While a variety of cognitive deficits and biases have been found to characterize aggressive and delinquent children and youth, very little attention has focused on determining whether aggressive youth also display deviant attributional beliefs in response to social failure. Research in the more impersonal cognitive domains such as achievement has shown attributions for failure to be potent determinants of both affective reactions and subsequent responding. Thus, the present study was designed to investigate whether specific attributional patterns following social failure may also relate to aggressive behavior. The aim of this study was to determine the relation between the level of self-reported physical aggression and specific attributional patterns following hypothetical social failure in a sample of incarcerated delinquent males. While the general hypotheses were that increased aggressiveness would be related to a greater tendency to endorse attributions for social failure that are external, stable, and controllable, only the hypothesis with regard to controllability was supported. The findings are discussed in terms of the relation between cognition and aggression in delinquent youth. PMID- 2246429 TI - Sustained attention in normal and in reading-disabled youngsters with and without ADDH. AB - Three groups of children-one normal, one reading-disabled, and one reading disabled with an additional diagnosis of attention deficit disorder with hyperactivity (ADDH)-were administered the Continuous Performance Test and compared on correct detections and three types of commission errors. All three groups showed a decline in sustained attention over the course of the task but not differentially according to diagnostic group. When younger and older subgroups were compared, the reading-disabled children were found to make significantly more correct detections with increased age, but not when the reading disability was accompanied by ADDH. The latter group of children also were differentiated by a type of commission error, previously associated with impulsive responding, that remained prominent in the older subgroup of dually diagnosed children. Reading-disabled children were differentiated by a second type of commission error which possibly was associated with inattention or short term memory deficit and which diminished with age. PMID- 2246430 TI - Peer Nomination Inventory of Depression: characteristics in a Spanish sample. AB - The Peer Nomination Inventory of Depression (PNID) was answered by 1,121 children from Barcelona in the fourth year of grammar school and by their teachers (n = 36) to analyze this questionnaire in a Spanish sample. The results indicated (1) high internal consistency; (2) discriminative power between depressed and nondepressed; (3) low concurrent validity; (4) convergent and discriminant validity; (5) a two-factor structure; and (6) that two discriminant functions could differentiate between depressed, dysthymic, and nondepressed subjects. The teacher's responses showed (1) moderate internal consistency; (2) discriminative power between depressed and nondepressed groups; (3) moderate concurrent validity; (4) and that two discriminant functions could differentiate between the diagnostic groups. The importance of the information given by the teacher to help detect severe depressive problems was pointed out. PMID- 2246431 TI - The internal consistency and concurrent validity of a Spanish translation of the Child Behavior Checklist. AB - The Child Behavior Checklist's applicability to a Hispanic sample was assessed by an examination of the instrument's internal consistency and concurrent validity. The CBCL and TRF were administered to a community sample representative of children of Puerto Rico aged 4 to 16. Cronbach's alpha was used to assess the internal consistency of empirically derived scales. The relation of CBCL and TRF scores to clinical diagnosis, adaptive functioning, and need for services served as indicators of the concurrent validity of the instrument's Spanish version. The results indicate that the total behavior problem scores on the instruments are good continuous measures of maladjustment for children in Puerto Rico. A child with high values on the scales has a high probability of being classified as a case by a psychiatrist. High levels of internal consistency were found in most subscales. Only scales comprising low prevalence problems showed poor internal consistency. PMID- 2246433 TI - Maternal beliefs about adaptive and maladaptive social behaviors in normal, aggressive, and withdrawn preschoolers. AB - The purpose of this study was to compare mothers of normal, aggressive, and anxious-withdrawn preschoolers with regard to their beliefs about how socially competent behaviors are learned and their beliefs concerning the origins of two types of maladaptive behaviors--aggression and withdrawal. 121 mothers of 4-year olds were questioned about how they think social skills are acquired. They were also presented with descriptions of hypothetical incidents of peer-directed aggression and social withdrawal and asked what they would do about these behaviors, how they would feel about them, and how they would explain them. Children's social behaviors were observed during free play and rated by their teachers. A norm-based multitargeting procedure was used that resulted in the identification of 10 highly aggressive children, 6 highly withdrawn children, and 60 children who were average in social adaptation. Results indicated that mothers of withdrawn children were more likely than mothers of average children to believe that social skills should best be taught in a directive manner and that maladaptive behaviors should be responded to in a high-powered, coercive fashion. These mothers were also more likely than mothers of average children to indicate that they would feel guilty and embarrassed by displays of maladaptive behavior, and they attributed these behaviors to dispositional factors. Mothers of aggressive children suggested highly directive strategies to teach social skills, but were more laissez-faire than mothers of average and withdrawn children in their reactions to maladaptive behaviors. PMID- 2246432 TI - Maternal characteristics, ratings of child behavior, and mother-child interactions in families of children with externalizing disorders. AB - Relationships among maternal characteristics, ratings of child behavior, and observed mother-child interactions were examined in a sample of 40 4- to 12-year old children with externalizing disorders. Mothers and children were observed in a task interaction and mothers provided self-reports of depressed mood, parenting self-esteem, marital satisfaction, social support, and life stress. Child behavior was rated by both mothers and teachers. Several significant correlations were found among observed mother and child behaviors and among maternal self report measures. However, few significant relationships were found between maternal characteristics and observed mother or child behavior. Although life stress predicted increased child negativity, maternal depressed mood was related to more appropriate child behavior. Mother and teacher ratings of child behavior demonstrated few significant relationships with other measures. These results suggest that, in samples comprised primarily of children with attention deficit disorder from socially advantaged families, few relationships exist between maternal characteristics, parenting behavior, and child behavior. PMID- 2246434 TI - Inattentive and noninattentive ADHD children: do they constitute a unitary group? AB - Teacher-rated ADHD and normal control children were administered a continuous performance test (CPT), and were then further subdivided based upon the presence or absence of objectively assessed attentional deficits. In addition, children were assessed using several measures of cognitive and behavioral functioning. Attentional deficits were significantly more prevalent among the ADHD group, but about half of the ADHD children showed no evidence of objectively assessed attentional dysfunction. Further group analyses indicated that ADHD children with objectively assessed attentional dysfunction appeared cognitively impaired, while ADHD children without objective evidence of attentional dysfunction had more conduct problems. CPT inattention was not related to the presence of cognitive impairments or conduct problems in the control group. These data must be considered preliminary because teacher ratings were the only source of diagnosis and a single measure of inattention was used. However, they suggest that two subtypes of ADHD children can be identified, one characterized by inattention and learning problems, and the other by conduct problems. PMID- 2246435 TI - Reward dominance and passive avoidance learning in adolescent psychopaths. AB - This study tests predictions that adolescent psychopaths are hyperresponsive to rewards (Quay, 1988) and deficient in passive avoidance learning (Newman & Kosson, 1986). Forty male adolescent juvenile offenders were divided into psychopaths and nonpsychopaths using cluster analysis. Subjects were administered a passive avoidance learning task which required learning when to respond to cards associated with either reward or punishment. Results showed a greater responsivity to reward in psychopaths, with no group differences in passive avoidance errors. Results lend support to the view that psychopaths tend to focus on the prospect of reward under conditions of mixed incentives and, when sufficiently motivated, are capable of improved performance. Together with findings of recent psychophysiological studies, these results suggest that adolescent psychopaths may have latent abilities which could have treatment implications. PMID- 2246436 TI - Research in college health. I: An introduction to the research process. AB - College health professionals are often intimidated by the research process and thus miss opportunities to develop and communicate their ideas. The present article, the first in a series on college health research, describes the basics of the research process, including the purpose and nature of research and the ways in which ideas are developed into research hypotheses. The process of reviewing research literature is described in detail, including methods for computerized searching. PMID- 2246438 TI - Psychotherapy and career counseling: toward an integration for use with college students. AB - The authors suggest that psychotherapy and career counseling with college students can be identified as potentially concurrent and interactive processes. They seek to increase awareness of this connection and underscore the value of its application when it is appropriate to do so. Selecting a career is a crucial developmental task for young adults and is, to varying degrees, an integral part of their psychosocial adjustment. The literature is reviewed from five perspectives: the psychodynamic model of career counseling; case examples; integration of career counseling and psychotherapy; a review of the developmental theories of Erikson, Farnsworth, Chickering, and Medalie; and empirical justification. The authors discuss the rationale for merging student psychotherapy and career counseling and offer case examples. PMID- 2246437 TI - Banning alcohol in a major college stadium: impact on the incidence and patterns of injury and illness. AB - To evaluate the effect of banning alcohol on the incidence of injuries and illness among spectators, we reviewed 4 years (1983 to 1986) of medical incident reports from a major collegiate football stadium. At no time had alcoholic beverages been sold inside the stadium, but before 1985, fans were allowed to bring alcohol into the stadium. In 1985, this practice was banned. During the study period, 340 medical incidents (M = 12.6/game) were reported. Several alterations of specific injury/illness patterns were noted after initiation of the ban: heat-related illness occurred more frequently before initiation of the ban, whereas extremity injuries and syncope (fainting from coronary insufficiency) occurred with greater frequency afterwards. The injury/illness rates per 10,000 fans were 2.95 in 1983, 2.45 in 1984, 1.92 in 1985, and 3.48 in 1986. There was no significant change in the overall incident rate after the ban. Evaluation of medical incidents revealed an alteration in specific injury/illness patterns but no change in overall incidence after institution of the ban. Future investigations are needed to elucidate more clearly the impact of banning alcohol on injury/illness rates and patterns at mass gatherings. PMID- 2246439 TI - Poliomyelitis in the United States: a historical perspective and current vaccination policy. PMID- 2246440 TI - A college health service's response to sexual assault issues. PMID- 2246441 TI - Dental health of university students in Finland. PMID- 2246442 TI - Staying well in the USA. PMID- 2246443 TI - Dietetic profession must recruit quality individuals. PMID- 2246444 TI - Cajun RD comments on Cajun/ethnic cuisine. PMID- 2246445 TI - Problems in using Comstock scale with visual estimation of plate waste. PMID- 2246446 TI - Living arrangements and dietary quality of older U.S. adults. AB - The association between living arrangement and dietary quality of older U.S. adults was investigated in 4,402 adults aged 55 years or older who participated in the Nationwide Food Consumption Survey, 1977 to 1978. Dietary quality was based on percent of Recommended Dietary Allowances for 3-day intakes of nine nutrients. More men living alone consumed a poor-quality diet than did men living with a spouse, particularly those 75 years or older; for women, this effect was seen only in the 55- to 64-year-old group. In general, more women than men had poor-quality diets. A number of factors (economic, employment, health status, energy intake, body mass index, and nutrient supplement use) were examined for their importance in accounting for differences in dietary quality of older men and women living alone compared with those living with a spouse. Energy intake was the most important variable accounting for the association of living arrangement with dietary quality. Evidence indicated that older adults living alone did not make poorer food choices than those living with a spouse, but rather that they consumed fewer calories. PMID- 2246447 TI - Accuracy of telephone dietary recalls in elderly subjects. AB - Accuracy of telephone-administered dietary recalls was determined for 159 elderly subjects by comparing the telephone recalls of single midday meals consumed at congregate meal sites with data on actual intake for the meals. Accuracy was determined for kinds of food eaten, size of portions eaten, and content of 15 nutrients. Exact agreement between the two data sources on the kinds of food eaten occurred for only 55% of the observed food items. For 5 of the 10 food groups evaluated, the bias in mean recalled portion-size data was less than 10%. There was evidence of attenuated regression slopes relating recalled to observed portion sizes for 4 of the 10 food groups; adjusted r2 values for the recalled portion sizes ranged from 0.02 to 0.94. Because errors in the recalls of the kinds and amounts eaten tended to go in different directions, the accuracy of the nutrient data was better than that for the food-item or the portion-size data. For 12 of the 15 nutrients evaluated, the bias in mean recalled intake data was less than 10%. Although the adjusted r2 values for the recalled nutrient data ranged from 0.24 to 0.58, there was evidence of attenuated regression slopes relating recalled intake to observed intake for only 5 of the 15 nutrients. We conclude that telephone contact is an acceptable way to obtain short-term dietary recall data from elderly subjects. PMID- 2246448 TI - Feeding the Hispanic hospital patient: cultural considerations. AB - As service-oriented professionals in a multicultural society, dietitians must be aware of cultural influences on food consumption patterns, population demographics, and health care usage by ethnic groups. The United States has one of the largest Hispanic populations in the world. The major health problems in the Hispanic population are cardiovascular disease, diabetes mellitus, and obesity. The use of health care services by Hispanic subgroups is dependent upon their residence in a rural or an urban area. This article summarizes national trends in food consumption, health care usage, prevalent health problems, and eating habits of Mexicans and Puerto Ricans, the most populous of the Hispanic subgroups. We provide diet modifications for energy-, fat- and sodium-restricted diets, which are part of the treatment for problems prevalent in this ethnic population. Dietitians must consider cultural and demographic influences to help Hispanic hospital patients modify their diet in ways that are both healthful and culturally acceptable. PMID- 2246449 TI - Consumers' perceptions of hospital food and dietary services. AB - Consumers' perceptions of the quality of hospital food, food-related service, clinical service, and their importance were determined through telephone interviews with 223 adults randomly selected from an urban county in Ohio. Respondents (greater than 65%) indicated that hospital food was of good quality for characteristics of taste, aroma, appearance, tenderness, cold temperature, freshness, and nutrient value. A substantial majority (greater than 74%) said that foodservice was dependable and accurate and that foodservice employees were helpful, cheerful, and considerate. These food and service characteristics were thought (greater than 71%) to be important to hospital meals, and a very large number (greater than 87%) of respondents considered these characteristics to be important to their hospitalization. About half (50.2%) viewed them as important in selecting a hospital. More than 82% thought registered dietitians were informative, helpful, and available to educate patients. Almost all (greater than 95%) considered nutrition counseling important to health care in the community. Of 17 quality characteristics considered, 14 were positively correlated (p less than .05) with the level of satisfaction with hospitalization. The three characteristics that were not significantly correlated with satisfaction were cold food being at the right temperature, meals looking delicious, and employees being cheerful. PMID- 2246450 TI - Dietary practices and concerns of adult urban black men of high socioeconomic status. PMID- 2246451 TI - Consumer preference for pork loin roasts cooked to 160 degrees F and 185 degrees F. PMID- 2246452 TI - Availability of knowledgeable informants for a psychological autopsy study of suicides committed by elderly people. AB - Psychological autopsy methodology has not been applied in studies of elderly suicides, despite the fact that the elderly are associated with a higher rate of suicide than any other age group. One school of thought argues that older adults who die by suicide are socially isolated and/or estranged for a long period of time before death, so that knowledgeable informants are difficult or impossible to obtain. In the present retrospective study we examine the number and availability of knowledgeable informants for 145 older people who committed suicide. We believe that the ability to access several motivated informants per case is essential to any psychological autopsy study by modern standards. The stereotype of the "average expectable" elderly suicide victim as socially isolated and living alone or in an institutional setting was not supported by our findings; an unexpectedly high percentage of subjects were married at the time of their death. There was at least one knowledgeable informant in 90% of cases and two or more in almost 50%. In 46%, the subject had expressed despondency over illness. In a prospective study involving interviews with informants for eight subjects, all eight had at least two knowledgeable and willing informants. Two cases of the eight are presented to illustrate the role of delirium and an ominous diagnosis (cancer) as causes of suicide. We conclude that it is feasible to do a psychological autopsy study of elderly suicides. PMID- 2246453 TI - Disturbance in daily sleep/wake patterns in patients with cognitive impairment and decreased daily activity. AB - The sleep/wake patterns of 121 chronically ill, mentally and physically handicapped patients were visually monitored hourly for 14 consecutive days. Four types of sleep/wake patterns were found. In order to investigate how cognitive and physical functions correlated with sleep disorders, patients were classified based on a scale of mental function and the grading of daily activity. The percent of total sleep hours and the sleep rating, showing disturbances in sleep/wake pattern, were evaluated. We found a high degree of individuality in sleep/wake patterns. Sleep disturbance was associated with daily activity as well as with cognitive impairment. This monitoring system provides medical personnel with valuable information for clinical management. PMID- 2246454 TI - The accuracy of medication histories in the hospital medical records of elderly persons. AB - Medication histories written in medical records are important sources of information for clinicians and researchers. Medication histories in outpatient records are frequently inaccurate; the accuracy of the histories in hospital records has not previously been studied. We evaluated the accuracy of medication histories recorded in hospital medical records of 122 persons over the age of 65 at three sites, comparing the written record to a structured history obtained from the patient by the research staff. We defined an error as either the failure to record the use of a medication the patient claimed to use or the recording of a medication that the patient denied using. We found that 83% of all patients had at least one such error, and 46% had three or more. We reanalyzed the data excluding over-the-counter, tropical, and cold medications, and found that 60% of all patients still had at least one error, and 18% had three or more. Failure to record use in the record was more common than recording medications the patient denied using. There were no qualitative differences between hospitals or between the histories obtained by interns and attending physicians. This analysis suggests that medication histories in the hospital medical record are not accurate sources of information in elderly persons. Errors in the history may adversely affect clinical care; researchers relying on hospital medical records to determine medication use at the time of admission should first validate their data. PMID- 2246455 TI - Are stressful life events risk factors for herpes zoster? AB - To determine if psychologically stressful life events are risk factors for herpes zoster, we conducted a case-control study of zoster and self-reported recent negative life events and major changes in spousal relationships. The subjects were 101 healthy community-dwelling cases of zoster and 101 healthy controls matched for age, sex, and race and generated by random digit dialing. The Geriatric Scale of Recent Life Events was administered to case and control subjects, and additional questions were asked regarding the perception of the life event. The results showed that case subjects experienced negative life events significantly more often than subjects in the control groups in the 2 months before zoster onset by analysis of discordant pairs (26 versus 10, odds ratio 2.60, 95% confidence interval [CI] 1.13, 6.27, P = .012), 3 months before (29 versus 11, odds ratio 2.64, 95% CI 1.20, 6.04, P = .007), or 6 months before (35 versus 16, odds ratio 2.00, 95% CI 1.04, 3.93, P = .012). The mean number of total life events was significantly higher in cases at 6 months before zoster (case means = 2.64, control means = 1.82, P = .008), but there were no significant differences at 2, 3, or 12 months before. There were no significant differences between case subjects and control subjects for spousal events, or any given single life event. In conclusion, we found that whereas patients with herpes zoster experienced the same kinds of life events in the year preceding the illness as did control subjects, recent events perceived as stressful were significantly more common among patients with zoster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246456 TI - Lack of association between medication use and the presence or absence of bacteriuria in elderly women. AB - This study was undertaken to determine if there is an association between medication use and the presence or absence of bacteriuria in elderly ambulatory women. Of 198 women who participated in three urine culture surveys (every 6 months) during the 18-month study period, 66 (34.4%) had bacteriuria on at least one survey. Both univariate and multivariate analyses for the demographics, age, place of residence, and medication use (by drug class) revealed that only place of residence had a significant association with the presence or absence of bacteriuria. In this regard, bacteriuric subjects more commonly resided in the nursing home and less commonly lived in the apartment-house complex compared with nonbacteriuric subjects (P less than .05). Therefore, this study demonstrates that in elderly ambulatory women, medication use does not appear to be associated with the presence or absence of bacteriuria. PMID- 2246457 TI - Absence of significant bacteremia during urinary catheter manipulation in patients with chronic indwelling catheters. AB - The objective of this study was to quantify the microorganisms present in blood at urinary catheter removal and at reinsertion in patients with chronic indwelling urinary catheters. This was a prospective study during a 4-month period at a university-affiliated geriatric medical center. Our subjects were 33 patients with chronic indwelling urinary catheters and positive urinary cultures; the urinary catheter was usually changed once a month. A peripheral vein line was used for blood withdrawal and urinary cultures and quantitative blood cultures (Isolator) were performed during and shortly after urinary catheter removal and insertion. All patients had significant bacteriuria (greater than 10(5) cfu/mL) with an average of 2.3 microorganisms. Among the 46 sequential quantitative blood cultures performed, only two patients had bacteremia from the urinary source and at a very low concentration; one patient had 0.13 cfu/mL Str. faecalis in blood 5 minutes after removal of the urinary catheter, and the other 0.1 cfu/mL Proteus mirabilis 5 minutes after reinsertion of a new urinary catheter. None of the patients had any subjective or objective clinical problem during the 36 hours after the urinary manipulation. Clinical symptoms and bacteremia are rare events, and prophylactic antibiotics do not appear necessary during urinary catheter removal and reinsertion in elderly institutionalized patients. Further studies are necessary to identify risk factors in the rare instances of patients with bacteremia. PMID- 2246458 TI - Clinically inapparent (asymptomatic) bacteriuria in ambulatory elderly men: epidemiological, clinical, and microbiological findings. AB - In a prospective longitudinal study, ambulatory elderly men were followed from 1 to 4.5 years to gain insight into the prevalence rates, clinical characteristics, and patterns of clinically inapparent (asymptomatic) bacteriuria (CIB). The prevalence of CIB was 12% (29/238) and increases with age. Unlike the gram negative organisms that cause overt urinary tract infection in this age group, gram-positive organisms dominated the CIB group. Both the CIB and abacteriuric patients have multiple chronic medical conditions and are indistinguishable on that basis. Twenty-nine elderly men with bacteriuria and 105 abacteriuric subjects were followed with serial urine cultures. During the study period the bacteriuric subjects exhibited spontaneous temporary or permanent resolution (76%, 22/29), intermittency (21%, 6/29), and probable bacterial persistence (38%, 11/29). No consistent pattern of bacteriuria was evident. Therefore, antimicrobial therapy is not warranted in the treatment of asymptomatic or clinically inapparent bacteriuria in ambulatory elderly men. PMID- 2246459 TI - What practicing physicians in North Carolina rate as their most challenging geriatric medicine concerns. AB - We recently surveyed a random sample of 500 physicians in family practice, general practice, and internal medicine in North Carolina, to discover their most challenging geriatric concerns. Using a three-stage survey technique, respondents were asked to answer two open-ended questions about the most challenging geriatric problems they face and what specific geriatric content areas would attract their participation in an educational program. They were then asked to rank 34 topics on which they would like more information. A total of 242 responses were received for a 55% response rate (63 of the 500 were undeliverable). Responses indicated that physicians are more concerned with management than diagnosis and revealed considerable evidence of empathy and concern. The top three topics had to do with the management of dementia, multiple problems, and depression. Approximately 25% of physicians consider problems of financing health care as among the most challenging problems. PMID- 2246460 TI - Delirium: masquerades and misdiagnosis in elderly inpatients. AB - Delirium is an organic mental disorder defined as transient, fluctuating global dysfunction of cognition. It is common in elderly medical inpatients, yet its varied presentation is often missed or misdiagnosed. PMID- 2246461 TI - Oral diseases in older adults. AB - In the case presented, a 65-year-old man with multiple dental, medical, and social problems benefited from interdisciplinary assessment and treatment. Despite his poor oral-health status and oral-health behaviors upon admission, patient education and dental therapy resulted in improved daily oral hygiene, elimination of oral diseases, and improved oral function. The overall quality of life of any individual, particularly an older one, can be enhanced through oral disease prevention, health promotion, and, when indicated, dental therapy. This patient was treated in a hospital environment with a well-established team approach to geriatric care. However, regardless of the care setting, the physician can play a key role in improving the oral health status and quality of life of older adults by including an oral screening examination as part of the periodic comprehensive geriatric assessment, recognizing oral pathology, requesting dental consultations and encouraging appropriate dental service utilization. PMID- 2246463 TI - Effects of diltiazem on urinary incontinence. PMID- 2246462 TI - Improving advance directives for healthy older people. AB - The quality and quantity of advance directives for healthy older people need to increase. Quality will improve with literal interpretations of do-not-resuscitate orders and more comprehensive directives. Changing the term "DNR" to "No ACLS (Advanced Cardiac Life Support)" should discourage health-care providers from subsuming other limitations under the directive to withhold resuscitation. Other aggressive medical and surgical interventions should be prospectively considered in addition to resuscitation. The quantity of advance directives will increase when physicians feel motivated to devote time and expertise to thorough discussions of advance directives. Although education and legislation will motivate physicians to some extent, their roles are limited. Fair reimbursement for this primary-care service is the most effective motive. The initial investment by Medicare may save large sums in the long run by reducing expensive, undesired care for older people. PMID- 2246464 TI - Accomplishments of the frail-old. PMID- 2246465 TI - Salmonella outbreak in a nursing home. PMID- 2246466 TI - A walking program improves gait and balance in nursing home patients. PMID- 2246467 TI - HIV-related diseases and AIDS. PMID- 2246468 TI - Monocular simultaneous refraction. AB - A system was developed to give an alternative to the standard Jackson Cross Cylinder test. This system eliminates the major difficulty of the Jackson Cross Cylinder test, which is alternative viewing of the images. The advantages of this system are: 1) ease of patient choice, 2) speed of testing, 3) patient preference, and 4) ease of understanding the test. The major disadvantage of this test system was that a few patients had difficulty viewing two images. Most difficulties could be easily resolved by a variation in the examination technique. (It helped if the patients were told they would now see double, or two rows of letters.) Occasionally, patients who had a field loss found this test difficult. The second problem was similar to one encountered with the Jackson Cross Cylinder test in that some patients would report one target clearer, regardless how one changed the lens. This was overcome by turning the testing lens system over so that the testing lens on the bottom was now on the top. Recently, we have relied only on the MSR technique as our subjective refraction, and the final prescription was based on it. These patients have reported no problems and have had good acuities. The MSR technique, when tested on a large number of patients, is demonstrated to be both efficient and reliable. The simultaneous refraction technique is not meant to be used to the exclusion of all other cylinder subjective tests, but, rather as an adjunct to our standard technique when conditions warrant its use. PMID- 2246469 TI - Pupillary dilation and fundus abnormalities. PMID- 2246470 TI - Neurological manifestations of AIDS. AB - HIV-infected patients are at increased risk of neurological disease. The most common symptom is an altered mental status, depicted by the progressive chronic stages of AIDS Dementia Complex. The ability to recognize this syndrome so as to be able to refer for evaluation is a key factor in the optometrist's role as primary care provider. PMID- 2246471 TI - Subconjunctival and external hemorrhage secondary to oral anticoagulation. AB - Recurrent, bilateral, and severe conjunctival hemorrhages mandate the search for an underlying etiology, such as a blood dyscrasia, blood clotting disorder, or recurrent increased intrathoracic pressure caused by repetitive vomiting or coughing spells. Medical and ophthalmic management is discussed in a case of subconjunctival and external hemorrhage from the eye secondary to prolonged prothrombin time in oral anticoagulation therapy. PMID- 2246472 TI - The optical characteristics of aiming scopes in archery. AB - Technical advancements in target archery have been extended to widespread use of "scopes" which magnify the target. In fact, these optical devices are simple converging lenses used at an arm's length from the eye. They produce a magnified image, but it is an image that suffers from significant dioptric blur, diminished somewhat by use of a peep sight in the bowstring which functions as an aperture stop. Visual acuities were taken with these scopes and, as might be expected, it was found that subjects saw no better with them. With the highest power scopes, acuity actually decreased. Experienced archers did slightly better with these aids than those with no archery experience. PMID- 2246473 TI - An epidemiological study of the ocular and visual profiles of Oklahoma Cherokees and Minnesota Chippewas. AB - Over the last three decades some American Indian tribes in North America have received attention in the literature as a minority group with unique visual characteristics. Studies on the refractive status of Indians have shown an increase of refractive errors and particularly an abnormally high prevalence, and amount of, with-the-rule astigmatism. These changes appear to have taken place over the last 40 years. Eskimos, on the other hand, have recently showed an astoundingly high incidence of myopia. Other Native American tribes do not show dramatic changes in myopia or astigmatism. The Public Health Service-Indian Health Service, as an ongoing aspect of their responsibilities to Native Americans, perform screenings on children. This study reports the results of visual screenings primarily of Oklahoma Cherokee and Minnesota Chippewa children. PMID- 2246474 TI - A brief history on the development of ophthalmic retinal photography into digital imaging. AB - A brief review is given of some of the important historical developments in ophthalmic imaging from Victorian times to the 20th century, and looks at the prospects of digital imaging as an alternative to conventional photographic methods of recording. PMID- 2246475 TI - Never mind the content, look at the edits: fundamentals of video editing. AB - There are many facets that go into the making of a good video programme. One of these is the editing, and the success of any programme very much depends upon the editing skills, a craft that can only be achieved by experience. This paper gives a brief but useful insight into some of the skills required. PMID- 2246476 TI - Specular microscopy at Southampton Eye Hospital. AB - There is nothing significantly new in the technique of specular microscopy. The equipment has improved and the methods of cell counting have been automated using computer technology. This paper gives an account of how the old practice is still being used effectively in assessing the endothelial cell population, their shape and shape variability. PMID- 2246477 TI - Demonstration of cerebral microemboli occurring during coronary artery bypass graft surgery using fluorescein angiography. AB - Coronary artery bypass graft surgery is associated with an unacceptably high incidence of neurological and neuropsychological complications (Breur et al., 1981; Smith, 1988). The main cause of cerebral dysfunction following this type of surgery is probably cerebral microembolism (Dutton et al., 1974; Taylor, 1986). The eye is an outgrowth of the brain and therefore is uniquely suitable for the study of cerebral microcirculation. Retinal fluorescein angiography has been employed during this surgical procedure to demonstrate the changes which occur in the cerebral microcirculation during operation. PMID- 2246478 TI - Retina's eye view of the implant lens. AB - Using simple inexpensive equipment, still macro photographs were obtained of the ciliary body and lens capsule of donor eyes during the procedure of intraocular lens implantation. It is shown that implant lens loops, while correctly bag implanted, can catch in the ciliary sulcus. PMID- 2246479 TI - Cine photography of anterior segment fluorescein angiography of iris tumours. AB - A description is given of the apparatus and technique for carrying out cine photography of anterior segment fluorescein angiography with special emphasis on its application in the recording and diagnosis of iris tumours. PMID- 2246480 TI - International tuberous sclerosis conference. PMID- 2246481 TI - Progressive neuronal degeneration of childhood with liver disease (Alpers Huttenlocher syndrome): a personal review. AB - Thirty-two autopsied cases of progressive neuronal degeneration of childhood with liver disease are reviewed. The typical clinical course is intractable seizures and liver failure following a period of developmental delay and failure to thrive in early infancy, but some children first present with seizures. Characteristic changes on the electroencephalogram, loss of visual-evoked potentials, occipital atrophy on computed tomographic scan, and particular changes on liver biopsy may assist diagnosis. Most patients succumb in less than 3 years, but some have a protracted survival into their teens, and very rarely they may present in early adulthood. Liver pathology comprises fatty change, hepatocyte loss, bile duct proliferation, fibrosis, and often cirrhosis. Gradual progression can be followed in sequential biopsies. Macroscopically, the cerebral cortex is variably involved, but usually there is patchy thinning and discoloration, with a striking predilection for the striate cortex. Microscopic changes include spongiosis, neuronal loss, and astrocytosis, which progresses down through the cortical layers. All areas may be affected but the calcarine cortex is usually most affected. Etiology is still obscure, though mitochondrial and slow viral disorders have been postulated. PMID- 2246482 TI - 'Benign' familial neonatal convulsions. AB - Nine family members over five generations are described in whom convulsions occurred in the first week of life. Routine studies, including cranial computed tomography and electroencephalography, failed to reveal an etiology in the proband, nor was a specific etiology ever found in other affected family members. All affected individuals developed normally. Three had recurrent seizures outside the first year of life. This condition is of particular importance to those who care for infants with seizures. An appropriate family history should obviate the need for unnecessary diagnostic tests as well as prolonged anticonvulsant therapy, but counseling regarding the increased risk of subsequent seizures should be provided to affected individuals. PMID- 2246483 TI - Self-injurious behavior associated with clonidine withdrawal in a child with Tourette's disorder. AB - A 7-year-old boy with Tourette's disorder, atypical pervasive developmental disorder, borderline mental retardation, and a history of self-injurious behavior was treated for 21 months with clonidine transdermal patches at doses ranging from 0.1 to 0.5 mg weekly. When withdrawn from clonidine over 4 weeks to assess the need for continued therapy, the patient developed multiple self-destructive behaviors involving the theme of suffocation. The importance of careful clinical monitoring of the behavior of patients undergoing withdrawal from prolonged treatment with high doses of clonidine is emphasized. PMID- 2246485 TI - Myotonia congenita: Thomsen's, Bell's, or Leyden's disease? PMID- 2246484 TI - Positron emission tomography demonstrated localized luxury perfusion in subacute sclerosing panencephalitis. AB - Positron emission tomography (PET) was performed on two patients in different stages of subacute sclerosing panencephalitis (SSPE) and compared with the concurrent computed tomography (CT) findings and clinical status. Case 1, which was in stage II, showed luxury perfusion in the anterior half of the cerebrum and decreases of cerebral blood flow and oxygen metabolism in the right frontal watershed zone, where CT showed low density. Case 2, which was in stage III, showed marked decreases of cerebral blood flow and cerebral metabolic rate of oxygen in all regions except the occipital region. The present PET study demonstrated that SSPE showed inflammatory-destructive progression and rostral caudal progression. Further, it was suspected that low density on CT scan, especially in the watershed zone, resulted partly from disturbances in cerebral circulation. PMID- 2246486 TI - Shunt-related brain abscess and ascending shunt infection. AB - We report the fifth case of shunt-related brain abscess. Two prior cases have been associated with colonic perforation and infection with gram-negative enteric organisms. These cases strongly suggest that ascending shunt infection is possible despite bulk cerebrospinal fluid flow in the opposite direction and add to our understanding of shunt infections. PMID- 2246487 TI - The effect of gestational age at birth on somatosensory-evoked potentials performed at term. AB - Multimodality-evoked potentials are widely used in newborns to assess the maturation and integrity of the sensory pathways. Reliable normative data are needed to maximize the utility of this technique as a diagnostic and research tool. Several electrophysiologic studies on the maturational changes of the auditory brain-stem response have demonstrated that latency measurements decrease as a function of increasing conceptional age. However, maturational studies of the somatosensory-evoked potential, particularly in low-risk premature infants, are limited. The existing evoked potential literature in healthy newborns proposes that maturation of the central nervous system occurs at a predictable rate, irrespective of a given gestational age at birth. Behavioral studies of premature infants suggest that neurologic development may be altered by early extrauterine exposure. The purpose of this study was to determine whether brain stem auditory- or somatosensory-evoked potential conduction times were comparable in premature and full-term infants matched for conceptional age. The results of this study suggest that myelination is determined by conceptional age, independent of premature birth. PMID- 2246488 TI - The pattern of neural tube defects created by secondary reopening of the neural tube. AB - The usual location of human neural tube defects at the rostral or caudal end of the primary neural tube suggests they are caused by failure of closure of the neural tube. In this study, neural tube defects were created by surgical reopening of the neural tube of 3-day-old duck embryos in one of three sites: the forebrain, cervicothoracic region, or thoracolumbar region. It was determined that of the 31 survivors with forebrain incisions, 39% had exencephaly; of the 42 survivors with thoracolumbar incisions, 31% had myeloschisis; but of the 37 with a cervicothoracic incision, only 14% had exposed spinal cord. This indicates that a rostral-caudal distribution of neural tube defects can be seen in a model created by secondary reopening of the neural tube. PMID- 2246489 TI - Hypoplastic corpus callosum in ocular albinism: indication of a global disturbance of neuronal migration. AB - Ocular albinism is distinguished from the more common oculocutaneous albinism by the presence of normal pigmentation of skin and hair in the former condition. Recent studies of ocular albinism have shown that the hypopigmentation of the optic fundus is associated with a number of anomalies of neuronal wiring involving the visual system. We present a patient with ocular albinism who also has a hypoplastic corpus callosum as determined by analysis of midsagittal magnetic resonance imaging scans. Previous studies of the hypoplastic corpus callosum indicate that this anomaly is a defect in neuronal migration as well. The finding of a hypoplastic corpus callosum in a patient with ocular albinism suggests a more generalized defect in neuronal migration not limited to the visual system. PMID- 2246490 TI - Support groups for pediatric neurologic disorders. PMID- 2246491 TI - Motor unit potential analysis in carnitine palmitoyl transferase deficiency. PMID- 2246492 TI - Asymptomatic hyperCKemia: detection of an isolated carrier of Duchenne muscular dystrophy. PMID- 2246493 TI - Cimetidine 800 mg twice daily for healing erosions and ulcers in gastroesophageal reflux disease. AB - Although H2-receptor antagonists have been the mainstay of therapy for gastroesophageal reflux disease (GERD), none of these agents has been approved by the FDA as effective in healing lesions. Since proton pump inhibitors may be associated with long-term disadvantages, a healing regimen with cimetidine would be useful clinically. This multicenter, randomized, double-blind study was conducted to evaluate the efficacy of cimetidine 800 mg b.i.d. in healing lesions and in providing symptomatic relief in patients with ulcerative or erosive esophagitis. Patients with greater than or equal to 8 heartburn episodes during a 1-week screening period, reflux confirmed by esophageal pH monitoring, and esophageal ulcers or erosions confirmed by endoscopy were randomized to treatment with placebo or cimetidine for 12 weeks. Cimetidine provided significantly greater (p less than 0.01) improvement (74% vs. 51%) and complete healing (67% vs. 36%) of esophageal lesions than did placebo. In these patients with erosive or ulcerative esophagitis, the median time to achieve 24 h without heartburn was 13 days with cimetidine and 30 days with placebo (p = 0.01). The mean heartburn severity score in the cimetidine group decreased rapidly during the first week and was consistently lower than in the placebo group. Cimetidine, 800 mg twice daily, is effective in promoting healing of esophageal ulcers and erosions and in providing heartburn relief in patients with symptomatic erosive/ulcerative GERD. PMID- 2246494 TI - Endoscopic control of upper gastrointestinal bleeding. AB - It has been estimated that gastrointestinal (GI) bleeding occurs in more than 100,000 patients with peptic ulcer disease each year. In 75-80% of the cases, bleeding will be self-limited. A major predictor of persistent or recurrent bleeding is the magnitude of blood loss before the initial evaluation. Endoscopy has an important role in the evaluation of the patient with suspected or presumed upper GI bleeding. Active bleeding at the time of the endoscopy correlates with the more likely probability of persistent bleeding, which carries a higher morbidity and mortality. In addition, there has been continued interest in the finding of a visible vessel. Although there is some controversy as to what a visible vessel actually is and how closely observations will agree about its recognition, there is general agreement that it is an important endoscopic finding and that it carries a high likelihood of rebleeding. In addition to the finding of a visible vessel, many endoscopists feel that ulcers found in the posterior-inferior wall of the duodenal bulb and high on the lesser curve of the stomach should be considered in a separate category. Owing to their proximity to large vessels, some feel that endoscopic management carries a greater risk because of the possibility of inducing bleeding. A wide variety of endoscopic approaches are available for the therapy of upper GI bleeding. It is convenient to divide these therapies into four categories: (a) topical, (b) injection, (c) mechanical, and (d) thermal. Endoscopic therapy for bleeding ulcers has generally been performed with a high degree of safety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246495 TI - The clinical importance of drug interactions with antiulcer therapy. AB - The overall safety of a given drug is determined by its toxicity, side effects, and drug-drug interactions. Thus, a clarification of the mechanisms, importance, and clinical implications of any drug-drug interaction with antiulcer therapy is critical to the use of antiulcer medications. Drug-drug interactions may occur as a result of changes in absorption, metabolism, distribution, or excretion. Fortunately, drug distribution or protein binding is unchanged by antiulcer therapy. Antiulcer drugs may affect absorption by several mechanisms. Ionized medications may bind to the divalent cations of antacids and sucralfate to result in poorly absorbed complexes. Reduced gastric acid may decrease the absorption of medications that are weak bases while enhancing the absorption of weak acids. Drug absorption may be impaired by delayed gastric emptying. Several H2-receptor antagonists, including cimetidine and to a lesser extent ranitidine, and the proton pump inhibitor, omeprazole, may reduce the hepatic degradation of drugs metabolized by the cytochrome P450 system. The degree to which such agents alter drug metabolism is determined by the patient's age, genetics, duration of therapy, degree of cytochrome P450 binding, and the regimen. Because the clinical importance of this interaction cannot always be predicted, caution is recommended whenever drugs metabolized by this system are used concurrently. Development of an understanding of the ways in which drug metabolism interactions occur may lead to more effective and safe use of these medications. PMID- 2246496 TI - The gastrin hypothesis. Implications for antisecretory drug selection. AB - Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs. PMID- 2246497 TI - The Rose Case reconsidered: physicians, apothecaries, and the law in Augustan England. PMID- 2246498 TI - Friedrich von Muller of Munich and the growth of clinical science in America, 1902-14. PMID- 2246499 TI - Public health in practice: an early confrontation with the 'silent epidemic' of childhood lead paint poisoning. PMID- 2246500 TI - Social hygiene in Soviet medical education, 1922-30. PMID- 2246501 TI - Polyclonal activation of the murine immune system by an antibody to IgD. X. Evidence that the precursors of IgG1-secreting cells are newly generated membrane IgD+B cells rather than the B cells that are initially activated by anti-IgD antibody. AB - Injection of BALB/c mice with an affinity-purified goat antibody to mouse IgD (GaM delta) stimulates T cell-independent B cell activation as well as later T cell activation. Activated T cells then induce polyclonal differentiation of B cells into IgG1-secreting cells, which results in an approximately 100-fold increase in serum IgG1 level. It is not known whether the same B cells that are initially activated by GaM delta are the progenitors of the IgG1-secreting cells. To investigate this issue a system was developed in which CB20 mice, which are congenic to BALB/c mice but express Ig of the beta allotype rather than the BALB/c alpha allotype, were injected with GaM delta and simultaneously or subsequently also received BALB/c B cells. The IgG1 response generated by the donor BALB/c B cells was quantitated by an assay specific for IgG1 of the alpha allotype. Our experiments with this system indicate that: 1) BALB/c B cells transferred 2 days after CB20 mice were injected with GaM delta generate a much larger IgG1 response than do BALB/c B cells transferred simultaneously with GaM delta antibody; 2) B cells that express membrane IgD generate the great majority of this response; 3) differences in the magnitudes of the responses of BALB/c B cells transferred at different times after CB20 mice were injected with GaM delta antibody cannot be explained by differences in homing of the donor B cells to the host spleen or by short survival of donor BALB/c B cells after their transfer; and 4) the response made by donor BALB/c B cells transferred 2 days after CB20 mice were injected with GaM delta is proportionate to donor cell representation in the host spleen 1 day after their transfer, whereas the response made by donor cells transferred simultaneously with GaM delta is disproportionately small. These observations suggest that most of the IgG1 antibody made by GaM delta injected mice is generated by newly produced, mIgD+ B cells that appear approximately 2 days after GaM delta injection, rather than by those B cells that are present in the spleen at the time of GaM delta injection, and support the view that signals that induce B cell secretion of Ig require an interaction with at least partially activated Th cells. PMID- 2246502 TI - Serologic, biologic, and western blot analysis of a T suppressor factor with specificity for the hapten 4-hydroxy-3-nitrophenyl acetyl derived from serum-free medium. AB - A T cell hybridoma producing a T suppressor factor (TsF) with specificity for the hapten nitrophenyl was converted to long term growth in serum-free medium and its product tested by serology, bioactivity, and Western blot analysis. Results indicated that Ag-specific suppressive activity was present in serum-free medium and this TsF could exhibit the characteristics ascribed to it by various groups: it could bind nominal Ag with specificity, it was bound by anti-TsF mAb, and it could mediate Ag-specific suppression both in vivo and in vitro. Western blot and SDS-PAGE analysis of this purified TsF revealed a 43-kDa single chain protein. PMID- 2246503 TI - Triggering of the CD44 antigen on T lymphocytes promotes T cell adhesion through the LFA-1 pathway. AB - The CD44 molecule, a molecule which has been previously known as Hermes, Pgp-1, extracellular matrix receptor III, and In(Lu)-related p80, is currently thought to be involved in several steps of normal immune cell function, including lymphocyte adhesion to high endothelial venules and to the extracellular matrix and T cell activation. We now demonstrate that triggering of CD44 on T lymphocytes by anti-CD44 mAb promotes cell adhesion. The induced homotypic adhesion is mediated by lymphocyte function-associated antigen-1 (LFA-1), because it was inhibited by anti-LFA-1 antibodies and not by anti-LFA-3 antibodies. This notion is supported by the temperature and Mg2+ dependence which is characteristic of LFA-1-mediated adhesion. Moreover, the sensitivity of CD44 induced adhesion to AMG and H7, which both prevent the activation of protein kinase C, and to cytochalasin B, which inhibits microfilament formation, suggests that the activation of the LFA-1 pathway via CD44 involves protein kinase C activation and requires an intact cytoskeleton. PMID- 2246504 TI - Rapid stimulation of large specific antibody responses with conjugates of antigen and anti-IgD antibody. AB - Injection of mice with goat anti-mouse IgD antibody stimulates a large IgG1 anti goat IgG antibody response, as well as polyclonal IgG1 production. To determine if this phenomenon could be used to induce large antibody responses to other Ag, covalent conjugates were produced between BSA or other Ag and H delta a/1, a mAb specific for IgD of the a allotype, and between BSA and AF3.33, a mAb specific for IgD of the b allotype. Injection of H delta a/1-BSA into BALB/c mice, which express Ig of the a allotype, or into (BALB/c x CB20)F1 mice (a x b allotype heterozygotes) induced IgG1 anti-BSA antibody responses that peaked 8 to 9 days after injection, and were more than 1000 times larger than those induced by injection of BSA alone, and 100 times larger than those induced by injecting unconjugated BSA plus H delta a/1. H delta a/1-BSA was no more immunogenic than unconjugated BSA when injected into CB20 mice, which express Ig of the b allotype, while AF3.33-BSA greatly enhanced anti-BSA antibody production in CB20, but not in BALB/c mice. Mice serially immunized with three different Ag conjugated to H delta a/1 made large antibody responses to all three Ag, provided that the mouse strain used did not recognize allotypic determinants on H delta a/1 as foreign and produce a neutralizing antibody response. Intravenous and s.c. routes of inoculation produced responses of similar magnitude and relatively low variability; responses to footpad or intramuscular inoculation were more variable, and i.p. inoculation induced smaller responses. Injection of BALB/c mice i.v. with 100 micrograms of H delta a/1-BSA induced an IgG1 anti-BSA response of 5.6 mg/ml, which was approximately 70% of the total IgG1 response. Anti-BSA responses to 30 micrograms of conjugate or less were much smaller, but could be considerably enhanced by adding unconjugated H delta a/1 to the inoculum. This system will be useful for the rapid stimulation of large antibody responses to biologically important Ag, and for investigating mechanisms of Ag processing and B and T cell activation. PMID- 2246505 TI - Bursectomy of chicken embryos at 60 hours of incubation leads to an oligoclonal B cell compartment and restricted Ig diversity. AB - Chickens that have been surgically bursectomized at 60 h of embryonic development usually generate Ig producing B cells; however, the bursectomized chickens are incapable of specific antibody responses, even after repeated immunization. In the present work, we analyzed the molecular basis of this immunodeficiency. In the bursectomized chickens, DNA sequencing revealed a repertoire of Ig L and H chains with a low number of different V-J and V-D-J joints, indicating an oligoclonal B cell compartment. In addition, the L and H chains belonging to each B cell clone had similar gene conversion events in the V region. In situ hybridization to Harderian gland tissue sections showed, that B cells of the bursectomized chickens were, however, capable of terminal plasma cell maturation. Thus, in chickens that were lacking the bursal microenvironment, 1) only a few B cell precursors differentiated into mature Ig-producing B cells, 2) low rate of gene conversion resulted in restricted Ig diversity. Regarding the chicken B cell differentiation, the present data support a model that the induction of B cell differentiation is a bursa-independent event, whereas the bursa of Fabricius has a crucial role in the amplification and diversification of the embryonic B cell repertoire. PMID- 2246506 TI - IL-5 induces a Pgp-1 (CD44) bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds to hyaluronate. AB - Pgp-1 expression was examined in unstimulated B cell populations and in B cells activated with several polyclonal stimuli. Flow cytometry analysis demonstrated that Pgp-1 expression increased when B cells were activated with supernatant of cloned Th2 cells, with LPS, or with IL-5, stimuli that induced polyclonal proliferation and differentiation. IL-5-primed B cells were phenotypically unique and could be divided into two distinct subpopulations based on the brightness of Pgp-1 expression. Furthermore, sterile sorting experiments showed that proliferating and differentiating B cells were highly enriched in a Pgp-1-bright, Ia-dull, B220-dull subpopulation. The possibility that Pgp-1 expressed on activated B cells functions as an adhesion molecule was evaluated by assessing adhesion of activated B cells to defined substrates. It was found that IL-5 activated B cells bound strongly to hyaluronate-coated surface, and this binding was specifically inhibited by anti-Pgp-1 Ab. These findings suggest that Pgp-1 expression is a useful marker which, under defined conditions, identifies the proliferating and differentiating subset of activated B cells. Moreover, the Pgp 1 bright subset of IL-5-primed B cells binds to hyaluronate in a Pgp-1-dependent manner that suggests a potential role of Pgp-1 in the in vivo adherence and trafficking of activated B cells. PMID- 2246507 TI - Differential inhibition of T and B cell function in IL-4-dependent IgE production by cyclosporin A and methylprednisolone. AB - The present study examines the role of the immunosuppressive agents methylprednisolone (MPN) and cyclosporin (Cs)A on IL-4-dependent IgE and IgG production. Addition of optimal amounts of IL-4 (100 U/ml) to cultures of tonsil mononuclear cells resulted in a mean increase in IgG production of 175% and in IgE production of 2460%. Frequency analysis of IgE- and IgG-producing B cells, using an ELISA spot assay, showed parallel increases in both Ig production and numbers of Ig-secreting B cells. IgE production was also enhanced by addition of IL-2 (10 U/ml) and maximal IgE production was obtained with a combination of IL-4 and IL-2. MPN (10(-7) M) and CsA (1 microgram/ml) markedly reduced IL4-induced IgE and IgG production as well as numbers of Ig-secreting cells in a dose dependent fashion. The suppression of Ig production by the cyclosporins was restricted to the immunosuppressive compounds CsA, CsG, and dihydro-CsD, but not the nonimmunosuppressive drug CsH. Delayed addition of CsA revealed that inhibition was maximal when the drug was added during the first 48 h after addition of IL-4 to the culture. Addition of IL-2 (10 U/ml) partially overcame the inhibition induced by CsA. In coculture experiments, in which separated T or B cells were precultured with the drugs and the cells were then combined and further incubated in the presence of IL-4, the suppressive effects of CsA on IgE production were related to pretreatment of the T but not B cells. The maximum inhibiting effects of MPN were similarly observed when the drug was present in the cultures from the beginning, and addition of IL-2 also partially reversed this inhibition. In contrast to the results with CsA, pretreatment of the B but not T cells with MPN-reduced IgE production. These studies demonstrate that IL-4 increases both numbers of IgE-secreting cells as well as IgE production and CsA and MPN differentially affect the responding T and B cells, resulting in inhibition of Ig production. PMID- 2246508 TI - Egr-1 expression in surface Ig-mediated B cell activation. Kinetics and association with protein kinase C activation. AB - We have studied the expression of an immediate/early type gene, Egr-1, in murine B lymphocyte responses to Ag receptor-generated signals. The Egr-1 gene encodes a zinc finger protein with sequence-specific DNA binding activity and is believed to act as an intracellular "third messenger," to couple receptor-generated signals to activation-associated changes in gene expression. We show here that Egr-1 mRNA expression is rapidly and transiently (returning to basal levels by 6 h) induced after receptor crosslinking with anti-receptor antibodies. Egr-1 protein expression is more prolonged, maintaining detectable levels through 12 h. The induction of Egr-1 is a primary response to Ag receptor signaling, as it is independent of new protein synthesis and is inhibited by actinomycin D. We have also examined the linkage of Egr-1 to known signaling pathways associated with G0 to G1 transition by these cells in response to signals generated through the B cell Ag receptor. Egr-1 mRNA was not induced after elevation of intracellular free Ca2+. In contrast, the pharmacologic agents PMA and SC-9, which directly activate protein kinase C, both cause marked increases in Egr-1 mRNA levels with the same kinetics as observed after anti-receptor antibody stimulation. Further, the protein kinase C inhibitors H7, sangivamycin, and staurosporin block anti receptor antibody-induced expression of Egr-1, thus, B cell Ag receptor-linked Egr-1 expression is likely coupled to the protein kinase C component of transmembrane signaling. Preliminary promoter mapping studies are consistent with this conclusion, because both PMA and anti-receptor antibody act through the same or overlapping cis-regulatory elements. PMID- 2246509 TI - Functional expression of HLA-C blank antigens on human blood lymphocytes. AB - The surface expression of two HLA-C blank Ag (Cb-1 and Cb-2) on PBL was investigated with Cb-1- and Cb-2-specific CTL clones generated by the stimulation of the HLA-C blank Ag on transfected Hmy2CIR cells. The Cb-1- and Cb-2-specific CTL clones could lyse EBV-transformed B cells and PHA-induced T cells from which the HLA-C blank genes were derived. Furthermore, the reactivity of these CTL clones with PHA-induced T cells was blocked by HLA class I monomorphic mAb. These results demonstrated that the HLA-C blank Ag are expressed on the surfaces of PBL. Thus, despite the fact that the HLA-C blank Ag are expressed on normal PBL, they are incapable of generating corresponding alloantibodies. On the other hand, the present study demonstrated that these Ag on normal PBL are able to induce specific CTL and that the capacity of these Ag to induce allogeneic CTL is almost identical to that of HLA-B Ag, indicating that they may function as alloantigens in vivo and play a significant role in the rejection of organ grafts and in the graft-versus-host reaction in bone marrow transplantation. PMID- 2246510 TI - [125I]fibrin deposition occurs at both early and late intervals of IgE-dependent or contact sensitivity reactions elicited in mouse skin. Mast cell-dependent augmentation of fibrin deposition at early intervals in combined IgE-dependent and contact sensitivity reactions. AB - When elicited in the skin of mice, either IgE-dependent immediate hypersensitivity reactions or T cell-dependent contact sensitivity (CS) reactions result in local extravasation of [125I]fibrinogen and deposition of [125I]fibrin. However, these two types of reaction differ in kinetics and in requirement for IgE, mast cells, or T cells. In the present study, we investigated the kinetics and magnitude of [125I]fibrin deposition in combined IgE-dependent and CS reactions elicited simultaneously at the same site and compared the results with those obtained when the two reactions were elicited at separate sites. We found that [125I]fibrin deposition in pure IgE-dependent reactions was greater at 2 or 6 h after challenge than at 24 h, but that significant fibrin deposition persisted at those sites 24 h after challenge. In CS reactions, [125I]fibrin deposition was detected as early as 2 h after challenge, indicating that fibrin deposition accompanies the "early component" of CS detected by Van Loveren et al. with the use of measurements of tissue swelling. But much more [125I]fibrin deposition was present in CS reactions at 24 h than at 2 or 6 h after Ag challenge. When IgE-dependent and CS reactions were elicited at the same site, [125I]fibrin deposition at early intervals (2 to 6 h) after challenge was increased three- to 25-fold compared with that seen in isolated CS reactions, but at 24 h the results in the combined reactions were virtually identical to those in CS responses. Studies in genetically mast cell-deficient and congenic normal mice indicated that mast cells were required for expression of the IgE-dependent augmentation of [125I]fibrin deposition observed at early intervals in combined IgE-dependent and CS reactions, but not for the [125I]fibrin deposition associated with "pure" CS reactions. These findings indicate that the net effect of IgE-dependent mast cell activation on CS responses is to increase the fibrin deposition associated with these responses, but this effect is appreciated only at early intervals after elicitation of the reaction. PMID- 2246511 TI - Hemorrhage in mice produces alterations in pulmonary B cell repertoires. AB - Nosocomial pneumonia occurs frequently after hemorrhage and trauma and contributes to the increased incidence of morbidity and mortality after severe injury. The production of secretory antibodies by mucosally associated B cells is an important component of pulmonary host defense mechanisms. To determine the effects of hemorrhage on pulmonary B cell function, we examined hemorrhage induced alterations in pulmonary B cell repertoires. There were no changes in the relative distribution of T or B cells among intraparenchymal pulmonary lymphocytes after blood loss. Hemorrhage induced decreases of between 5- and 10 fold in the frequencies and numbers of pulmonary B cell clonal precursors specific for the bacterial Ag levan and Pseudomonas aeruginosa polysaccharide. These decreases in numbers and frequencies of bacterial Ag-specific pulmonary B cell clonal precursors were present between 3 and 10 days after blood loss. Similar decreases in numbers and frequencies were found among pulmonary clonal precursors specific for the autoantigen mouse transferrin, but not for the autoantigen dsDNA or the external antigens OVA and keyhole limpet hemocyanin. These results demonstrate that hemorrhage produces marked alterations in pulmonary B cell repertoires, which may contribute to postinjury abnormalities in host defenses. PMID- 2246512 TI - Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. AB - By intrasplenic immunization we raised a rat mAb (mAb V1q; IgG2a, kappa) with a potent neutralizing activity against natural mouse TNF (1 microgram/ml mAb V1q/100 U/ml TNF). mAb V1q was used to study the role of endogenous TNF in experimental peritonitis induced by sublethal cecal ligation and puncture. mAb V1q persisted for over 5 days in the serum of mice injected with 100 micrograms of the antibody and, therefore, proved useful for in vivo experiments. As little as 20 micrograms mAb V1q/mouse prevented lethal shock of the animals by 400 micrograms LPS/mouse. In sublethal cecal ligation and puncture i.p. injection of mAb V1q directly and up to 8 h after induction of experimental peritonitis lead to death of the animals within 1 to 3 days. The lethal effect of mAb V1q was compensated by injection of recombinant mouse TNF. Similar mAb V1q effects as in immunocompetent mice were shown in severe combined immune deficiency mice deficient of mature functional B and T cells. Taken together, these data suggest that during the early phase of peritonitis endogenous TNF may stimulate nonlymphoid cells such as granulocytes, macrophages, platelets, and fibroblasts to ingest bacteria and to localize inflammation, respectively. These beneficial effects of TNF may determine survival. Thus, our data may have implications for the therapeutic management of a beginning peritonitis. PMID- 2246513 TI - Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. AB - Transforming growth factor beta 1 (TGF beta 1) has important effects on expression of the IgA isotype. TGF beta 1 alone, or in combination with IL-5 or IL-2 increases IgA secretion by populations of LPS-activated surface IgA negative (sIgA-) spleen B cells, while concurrently decreasing IgM and IgG secretion. The present study demonstrates the activity of TGF beta 1 as an IgA isotype switch factor at the clonal level. Stimulation of LPS-activated sIgA- spleen B cell populations with TGF beta 1, or a combination of TGF beta 1 and IL-2, resulted in a significant increase in total numbers of IgA secreting cells, and this increase ultimately was paralleled by an increase in total IgA secretion. Using limiting dilution analysis, TGF beta 1 was shown to increase the frequency of IgA secreting B cell clones, by approximately 20-fold. This was not accompanied by increased numbers of IgA secreting cells/clone. In contrast, IL-2 does not have activity as an IgA switch factor, but does increase IgA production by B cells already committed to secrete that isotype. Cell cycle inhibitors such as thymidine and hydroxyurea also selectively increased numbers of IgA secreting cells and total IgA secretion among populations of LPS-activated sIgA- spleen B cells. This suggests the IgA enhancing activity of TGF beta 1 may, in part, be related to its ability to inhibit cell growth. PMID- 2246514 TI - Growth factor-dependent differentiation along the myeloid and lymphoid lineages in an immature acute T lymphocytic leukemia. AB - Bone marrow cells from a child with an immature (CD2+, CD5+, CD7+) acute T lymphocytic leukemia (T-ALL) were cultured in the presence and absence of human rIL-2, IL-3, or granulocyte-macrophage (GM)-CSF. Cells cultured without growth factors failed to divide and those initiated in the presence of IL-2 or GM-CSF underwent maturation and terminal T lymphoid or myelomonocytic differentiation, respectively. In contrast, a permanent growth factor-dependent cell line, designated TALL-103/3, was established upon culture in IL-3. The TALL-103/3 cells gradually lost the T cell-specific markers and acquired a myeloid phenotype (CD15+, CD33+). Switching of the IL-3-dependent cells at an early passage to medium containing only human rIL-2 resulted in the establishment of a subline, named TALL-103/2, with a T lymphoid phenotype (CD3+, CD8+, TCR-gamma delta +, CD7+). The TALL-103/2 cells strictly require IL-2 for growth, are irreversibly committed to the lymphoid lineage, and cannot survive in the presence of any other hemopoietic growth factor tested so far. In contrast, the IL-3-dependent TALL-103/3 cells could be adapted to grow in synthetic (serum-free) medium also in the presence of either GM-CSF or IL-5, in which they retain a myeloid phenotype. Interestingly, after 18 mo in culture in IL-3, the TALL-103/3 cells can still be phenotypically converted to the lymphoid lineage upon addition of IL 2, thus maintaining its bipotentiality. Despite the marked phenotypic differences, the TALL-103/2 and TALL-103/3 cell lines show the same karyotypes with multiple abnormalities present in the primary malignant clone and have identical rearrangements of the TCR-gamma and -delta loci, thus confirming their derivation from a common precursor cell. Together, these findings indicate that the phenotype of immature T-ALL cells can be drastically modified by the presence of specific hemopoietic growth factors in the environment, leading to either lymphoid or myeloid lineage commitment while leaving their karyotype and genotype intact. PMID- 2246515 TI - IgG autoantibody activity in normal mouse serum is controlled by IgM. AB - In the serum of normal BALB/c mice, IgG antibody reactivity to mouse actin and tubulin, DNA, and TNP groups was very low compared to that of the IgM. This activity was considerably increased when IgG was separated, by affinity chromatography on protein A-Sepharose, whereas no difference in the IgM activity was observed. Addition of IgM to IgG isolated from the same serum resulted in the inhibition of IgG binding to these Ag. Isolation of IgG antibodies on actin, TNP, and tubulin immunoadsorbents has indicated that at least part of the IgG antibodies is polyreactive. In order to understand this inhibition better, experiments with F(ab')2 fragments of IgG were performed. IgM inhibited the binding of F(ab')2 to the antigens in a dose-dependent manner and reacted with immobilized F(ab')2. IgM isolated on F(ab')2 immunoadsorbent, as compared to the initial IgM preparation, were less active toward the Ag but more inhibitory for IgG binding to the Ag. In some pathologic situations, IgM failed to inhibit some IgG antibody activities. The anti-DNA IgG activity from (NZB x NZW)F1 mice was not affected by autologous IgM. Similarly the anti-tubulin IgG from mice infected with Trypanosoma cruzi were less inhibited by IgM from autologous serum than antitubulin IgG from normal mice. These results are compatible with the existence in normal mice of an idiotypic-like network, regulating via an IgM population in the serum, the binding of IgG autoantibodies to self Ag. Modifications of this idiotype-anti-idiotype system might lead to the expression and/or expansion of autoreactive IgG-producing clones. PMID- 2246516 TI - IgG-dependent generation of platelet-activating factor by normal and low density human eosinophils. AB - We have compared normal and low density human eosinophils for their ability to generate platelet activating factor (PAF) in response to IgG-dependent and nonimmunologic stimulation. After 45 min incubation with IgG-coated Sepharose beads the concentrations of cell-associated PAF recovered from normal density eosinophils were significantly greater than from low-density eosinophils or neutrophils. Moreover, eosinophils stimulated with calcium ionophore A23187 had a considerably greater capacity to generate PAF than had previously been described. Although the quantities of cell-associated PAF recovered from normal and low density eosinophils and neutrophils after A23187 stimulation were similar, the amounts of extracellular PAF recovered from both eosinophil populations were significantly greater than from neutrophils. The amounts of PAF recovered from the low density eosinophils may not reflect the full synthetic capacity of these cells, because PAF-turnover was found to be more rapid than that observed with normal density eosinophils. When exogenous [3H]PAF was added to the two stimulated eosinophil populations subsequent analysis of the [3H]PAF metabolites by DIOL-HPLC revealed that low density eosinophils incorporated PAF into the phosphatidylcholine (PC) pool more rapidly than did normal density eosinophils or neutrophils. Alkaline hydrolysis of the PC fraction from whole cell extracts followed by treatment with acetic anhydride resulted in all the PC-associated radioactivity being converted to [3H]PAF, confirming PAF incorporation to PC via this pathway. These findings suggest that the contribution of eosinophils to inflammatory processes through the generation of PAF may be greater than previously appreciated, and that Ig-mediated stimulation may be important in initiating generation of the mediator. Low density eosinophils, that are presumed to be similar to tissue eosinophils, may have a role in regulating PAF concentrations in tissues through their enhanced rate of metabolism. PMID- 2246517 TI - Identification of a polypeptide sequence that mediates nuclear localization of the acute phase protein C-reactive protein. AB - C-reactive protein (CRP) is the prototypic human acute phase serum protein. CRP binds to several nuclear Ag including chromatin, histones, and small nuclear ribonucleoproteins. Binding to sites of tissue inflammation and the nuclei of inflammatory cells has been demonstrated in vivo. We also noticed significant similarity between CRP and nucleoplasmin, a molecule with nuclear localization activity. We therefore decided to test whether CRP was capable of nuclear localization. CRP and the control protein human serum albumin were FITC conjugated and microinjected into living VERO cells. The cells were incubated at 37 degrees C for 15 min and then examined by fluorescence microscopy. Nuclear localization of CRP but not albumin was rapid and a high nuclear to cytoplasmic ratio was seen, consistent with active nuclear transport. Incubation at reduced temperature inhibited nuclear uptake by CRP. A synthetic peptide, RKSLKK, from the CRP sequence, when coupled to FITC-albumin, also mediated nuclear localization. Nuclear localization of the related protein, serum amyloid P component, was also seen and a homologous nuclear localization signal was identified. Because CRP was previously demonstrated to inhibit RNA transcription and enhance chromatin degradation it is proposed that CRP may play a unique role in injured cells to alter processing of damaged nuclei. Biochemical, structural and sequence comparisons between the CRP/serum amyloid P component family of proteins (pentraxins) and the nucleoplasmin/B23 family of proteins showed regions of sequence homology that may be related to their shared cyclic pentameric structure. PMID- 2246518 TI - Priming of the respiratory burst in human eosinophils is accompanied by changes in signal transduction. AB - Addition of platelet-activating factor (PAF) to human eosinophils leads to the modulation of eosinophil responses. The respiratory burst, induced by opsonized particles, consists of an initiation and a propagation phase and is greatly enhanced ("primed") after pretreatment with PAF. This priming event induces the following changes in signal transduction between the opsonin receptors (in particular the CR3 receptor) and activation of the respiratory burst: 1) an enhanced activation of protein kinase C (PK-C): the initiation of the respiratory burst in untreated eosinophils is not sensitive to PK-C inhibition (via staurosporine) and is not accompanied by accumulation of diglycerides and changes in [Ca2+]i. After pretreatment with PAF, the initiation of the response is partly sensitive to inhibition of PK-C (via staurosporine) and is accompanied by accumulation of diglycerides and a fast and sustained increase in [Ca2+]i; and 2) an enhancement of a PK-C-independent initiation of the respiratory burst. The propagation phase in both primed and unprimed cells is sensitive for inhibition by staurosporine. Our results indicate that in eosinophils the phospholipase(s) responsible for the accumulation of the diglycerides and changes in [Ca2+]i during the initiation phase of the serum-treated zymosan response seem(s) to become associated with the signal transduction route only after priming with PAF. This results in the occurrence of two signal transduction routes that can act independently of each other. PMID- 2246519 TI - Two isoforms of human membrane-bound alpha Ig resulting from alternative mRNA splicing in the membrane segment. AB - Antibodies specific for membrane-bound Ig (mIg) but not for their secreted forms would be useful not only for studying the function of mIg but also for modulating B cell activities in vivo. We have proposed that the extracellular portions of the membrane anchor peptides of mIg can be used as antigenic sites for isotype specific targeting of B cells. Clones containing the genes of human Ig alpha 1 or alpha 2 subclasses were isolated from a genomic DNA library. The gene segments encoding the membrane peptides and their flanking regions were amplified by polymerase chain reaction, subcloned into plasmid pUC19, and the DNA sequences were determined. Human alpha 1 and alpha 2 genes, like murine alpha gene, each has only one membrane exon. The sequences of the human alpha 1 and alpha 2 genes are almost identical in the membrane peptide-coding region. The mRNA from a human mIgA-expressing B cell line, DAKIKI, was isolated, its cDNA prepared, and the segments spanning the membrane peptide-coding region and a part of the constant domain 3 amplified by polymerase chain reaction. DNA sequences revealed that there are two isoforms of alpha 1-chain, resulting from the alternative splicing of the third constant domain of H chain to two acceptor sites in the membrane exon. One isoform has a segment of 32 and the other 26 amino acid residues in the extracellular portion of the membrane peptide. These segments may serve as isotype-specific antigenic epitopes for antibody targeting of mIgA-bearing B cells. PMID- 2246520 TI - Recognition of a B cell lymphoma by anti-idiotypic T cells. AB - Idiotypic IgM derived from a B cell lymphoma can act as a tumor-associated Ag, in that immunization with this purified protein generates an anti-idiotypic immune response that specifically suppresses tumor development. Spleens of immune mice contain T cells that proliferate in response to idiotypic IgM. However, idiotypic Ag is presented to the T cells most efficiently in its natural form at the surface of the lymphoma cells, than as soluble IgM plus presenting cells. Variant tumors that display either little or no idiotypic IgM at the cell surface, but which are otherwise indistinguishable from parental tumor, induce a weak response or fail to stimulate the T cells, respectively. Anti-idiotypic lines and clones have been derived from the splenic T cells by growth in the presence of irradiated tumor cells. Phenotypic analysis revealed that cells from both lines and clones express CD3 and CD4 Ag, but not CD8. Recognition of tumor Id, which required no added presenting cells, was inhibited by antibody against MHC class II Ag, and variably by anti-CD4. Proliferative responses were inhibited by anti idiotypic antibodies, but also by antibodies against the constant region of the mu H chain, indicating that perturbation of the surface IgM abrogates availability of idiotypic determinants to the T cells. PMID- 2246521 TI - Protein F: a novel F(ab)-binding factor, present in normal liver, and largely released in the digestive tract during hepatitis. PMID- 2246522 TI - [Two stages three fields lymph node dissection in esophageal cancer]. AB - In order to indicate the three fields lymph node dissection method to wider ranges of patients with esophageal cancer, the two stages technique was applied to those with moderate disturbance of general physical conditions. Fifty eight patients with esophageal cancer admitted to our clinic from January 1986 to December 1988 and 38, in whom those with cervical esophageal cancer were excluded, employed esophagectomy. Of them, 26 patients (68%) received the three fields dissection method, 13 being due to the one stage technique and the remaining 12 being due to the one stage technique and the remaining 13 being due to the two stages technique. The three fields dissection method was indicated to patients who were younger than 75 years of age, were expected to receive curative resections or had no, mild and moderate disturbances of the physical conditions. The one stage technique was applied to patients with no and mild disturbances of the physical conditions while the two stages technique was to those with moderate disturbance. The general physical conditions were evaluated with the past history, underlying diseases, functions of the main organs and the ability of host defense. In the first operation of the two stage technique, subtotal esophagectomy and dissection of the regional lymph nodes including the paratracheal ones were performed. After approximately one month, esophageal reconstruction with the gastric tube and dissection of the regional nodes of the abdomen and neck were done in the second operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246523 TI - [Clinical experience of mechanical ventricular support with centrifugal pump for severe ventricular failure after open heart surgery]. AB - Five adult patients (pts) with age 15-67 (mean 43) received mechanical circulatory support with centrifugal pump (Biomedicus, BP-80, Sarns centrifugal pump) for postcardiotomy profound shock. Three pts underwent left ventricular support (LVS) alone, and the other 2 required biventricular support (BVS). Duration of the LVS ranged from 33 to 240 hours (mean 126 hours) and the right ventricular support 92, 120 hrs. Pump flow rate was 1.1 to 2.5 (mean 1.9) L/min/m2. Sixteen pumps were used and the pump exchange was performed 9 times in five pts and an average perfusion time per pump was 57 hrs. Two of 3 pts with LVS alone survived and one died of multiorgan failure associated with right heart dysfunction. In two pts with BVS, one survived and the other died of persistent low cardiac output early after pump removal. As the complication during mechanical support, bleeding was seen in 3 pts and cerebral infarction in one. Although centrifugal pump has potential limitation in antithrombogenicity and durability, this device provides a simple and effective mechanical circulatory support. PMID- 2246524 TI - [Increase of surfactant and protein contents in the alveolar space after lung preservation]. AB - This study is to describe the pathophysiological change in the alveolar space due to reperfusion injury in the lung. Six pigs, weighing 20-22 kg, were used. Through the left lateral thoracotomy, both sides of pulmonary artery (PA) and bronchus (Br) were exposed and occluded the left side of PA and Br. Left lung was perfused with 200 ml of UCLA Formula and preserved in room temperature (27 degrees C) for 3 hours. After the clamps were released, right side of PA and Br were clamped and pulmonary artery pressure (PAP) and static lung compliance were measured in ischemic lung. Then, animals were sacrificed and alveolar wash was performed. With the fluid taken from the alveolar wash, the surfactant and protein content in the alveolar space were measured using Malate's method and Lowry's method, respectively. As the results, PAP (mmHg) was significantly increased after the reperfusion, from 34.0 +/- 8.1, to 85.4 +/- 8.7 (p less than 0.001). Lung Compliance (ml/cmH2O) was decreased, from 0.52 +/- 0.07 to 0.31 +/- 0.1 after the reperfusion (p less than 0.001). The content of surfactant in the left lung described as a ratio (left/right) was 252.5 +/- 87.8% of that in right side. The content of protein in the left lung was 289.5 +/- 137% of that in right side. We concluded that both contents of surfactant and protein were increased in alveolar space after the reperfusion. PMID- 2246525 TI - [Experimental reconstruction of the trachea with free jejunal graft]. AB - To evaluate experimentally the usefulness of the jejunum in the correction of extensive tracheal defect, circumferential tracheal defect was surgically created in 31 mongrel dogs and primarily reconstructed with microsurgical free tissue transfer of autogenous jejunal segment. A silicone T tube was inserted to maintain the lumen of the grafted jejunal segment. First, defect of 7 cervical tracheal rings was repaired with untreated 5 cm free jejunal segment in 12 dogs (group 1). Next, a pilot experiment to examine the quantity of intestinal juices from jejunal segments revealed that abrasion and cauterization of the mucosal surface decreased the secretion of intestinal juices, so defect of 7 cervical tracheal rings was repaired with 5 cm free jejunal segment the surface of whose mucosa was abraded and cauterized in 11 dogs (group 2). In all the dogs except two, primary healing was accomplished without air leakage or infection, and gross pathological examination of the trachea and graft revealed no evidence of disruption, infection or granulation. In group 1, 6 of the 12 dogs died of pneumonia or air way obstruction caused by intestinal juices from free jejunal segment within 20 days after the operation. On the other hand, only one of the 11 dogs died of pneumonia at 9 days in group 2. One of the dogs died of air way obstruction caused by mucus at 3 months. Three dogs died of filariasis at 4 weeks, 3 and 7 months, and 5 dogs were sacrificed at 2, 4, 8 weeks and 3 months. Microscopic examination of the graft demonstrated thin jejunal mucosa. The anastomosis was already covered with epithelium by the end of 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246526 TI - [The optional usage of blood cardioplegia through eleven-year experience of open heart surgery]. AB - We propose two clinical studies in this paper for the optimal usage of cold blood cardioplegia (CBC) to evaluate 1) the effects of increasing the volume of CBC, and 2) the optimal use of verapamil, on postischemic myocardial recovery. First, patients with valvular heart surgery were divided into three groups according to the initial dose of CBC: Group I, 5 ml/kg in 368 patients; Group II, 10 ml/kg in 41; and Group III, 12 ml/kg in 86. In all groups CBC was infused every 25 to 30 minutes. Although the preoperative conditions of Group III patients tended to be more serious compared to Groups I and II, there was no difference in cardiac related hospital mortality among the three groups. Second, 45 patients who had undergone valvular or coronary heart surgery were divided into three groups according to the usage of verapamil: Group A, infusion of verapamil of 1 mg/L into CBC; Group B, infusion of verapamil of 0.2 mg/kg into a perfusate; and Group C, the same method as Group B with additional administration of verapamil of 0.1 mg/kg into a perfusate at 60 minutes after the commencement of cardiopulmonary bypass and a continuous drop of 0.5 micrograms/kg/min for the succeeding 24 hours. Each group consisted of nine patients who had valvular surgery and six patients who had aorto-coronary bypass surgery. There was no difference in the severity of the patients' conditions between the groups. The optimal concentration during and after the operation and good clinical results were obtained in Group C. We conclude that the initial optimal dose of CBC is 12 ml/kg, and that the combination of an infusion of verapamil into a perfusate and a succeeding continuous drop is the appropriate method. PMID- 2246527 TI - [The experimental study for autoperfused heart-lung preservation--evaluation of pulmonary function after transplantation]. AB - Although various methods for keeping long term good pulmonary function have so far been studied, no reliable method for heart-lung preservation has been established yet. Recently, we aimed at heart-lung preservation using the autoperfusion method and mainly examined pulmonary function after transplantation. After preserving heart-lung organ blocks extracted from mongrel dogs by autoperfusion method, 10 left lungs (preserved for 6.8 +/- 0.8 h) were orthotopically transplanted and combined heart-lung transplantation was performed under extracorporeal circulation using 5 heart-lung grafts (preserved for 7.5 +/- 0.5 h). All of lung-transplanted dogs were alive; preserved lungs showed good gas exchange power from immediately after transplantation. Left lungs on the 3rd day showed normal histological findings and chest X-P also revealed good pneumatization of transplanted lungs. The heart-lung transplantation enabled 4 cases to be free from extracorporeal circulation and arterial blood gas analysis also revealed good results [PO2 396.5 +/- 34.7 mmHg, PCO2 35.5 +/- 6.9 mmHg (FiO2 1.0)]. Lung tissue findings after 6 hours from the above freedom showed slight edema alone. The above results suggested the effectiveness of the autoperfusion method for heart-lung preservation. PMID- 2246528 TI - [Peritoneal dialysis in neonates and infants after open heart surgery]. AB - Peritoneal dialysis was required in 20 (12.8%) of 156 neonates and infants for acute renal failure following open heart surgery using cardiopulmonary bypass. Cardiac diagnosis was TAPVD (7 cases), PA with IVS (2), ECD (2), coarctation of the aorta with VSD (2) and other cardiac malformations (7). The indication for dialysis was oliguria of less than 1.0 ml/kg over 4 hours resistant to volume repletion, inotropic agent and diuretics. Peritoneal dialysis was performed using dialysis catheter and glucose containing dialysis solutions. The mean predialysis BUN and serum creatinine were 30.4 mg/dl and 2.7 mg/dl respectively. The highest serum creatinine during dialysis was 4.5 mg/dl, and all but one patient had BUN level of under 100 mg/dl. Dialysis with glucose containing solution could allow sufficient fluid removal as a result, fluid overload was restored. Plasma protein and electrolytes balance were corrected within 48 hours. Two neonates and 4 infants survived. Thirteen patients died on dialysis: nine of those deaths were related to low cardiac output, 2 death were attributable to respiratory insufficiency, and 2 cases died due to sepsis. One infant died of an unexplained cardiac arrhythmia after renal failure had been improved. It is concluded that peritoneal dialysis is beneficial in neonates and infants who become oliguria following open heart surgery. PMID- 2246529 TI - [Extended hypothermic heart-lung preservation system for cardiopulmonary preservation with retrograde coronary sinus perfusion and lung immersion]. AB - One major restriction of clinical heart-lung transplantation has been the inability to provide extended hypothermic organ preservation. We examined whether core-cooling, retrograde heart perfusion and lung immersion could provide adequate cardiopulmonary preservation. Hence, donor dogs were placed on cardiopulmonary bypass, and rapidly cooled to 15 degrees C. Then heterotopic heart unilateral left lung transplantations were performed. In control group I (n = 5), hearts and lungs were harvested following core-cooling and cardioplegic arrest, and transplanted immediately. In experimental group II (n = 5), heart lung blocks were similarly excised but stored at 4 degrees C for 12 hours and then transplanted. During preservation, the lungs were immersed in the extracellular solution. For the heart, non-recirculating retrograde coronary sinus perfusion was performed with oxygenated intracellular solution containing perfluorochemicals. Myocardial function determined by the ratio of end-systolic pressure to end-systolic dimension in the experimental group was similar to that in controls. Although pulmonary vascular resistance and extravascular lung water of the experimental group was higher than those in control group, arterial oxygenation was similar in both groups. Thus, extended heart-lung preservation with core-cooling, retrograde heart perfusion and lung immersion technique could be achieved for heart-lung transplantation. PMID- 2246530 TI - [Brachial plexus injury and fracture of the first rib as complications of median sternotomy]. AB - In 192 patients following median sternotomy during from 1978 to 1988, we studied the incidence, cause, prognosis and correlation of brachial plexus injury and fracture of the first rib as complications of median sternotomy. Four brachial plexus injuries were identified, an incidence of 2.1%, seven first-rib fractures were identified, an incidence of 3.6% and one patient had both complications in this series. Symptoms of this patient were more severe and difficult to improve than those of patients without first-rib fracture. Stretching of the nerve by the displaced first rib, ischemia of the nerve by pressure on it, and direct injury by the fractured rib end are causes of the brachial plexus injury following median sternotomy. It is due to the difference of position of the fracture, the difference of direction and degree of the protrusion of the fractured rib end, whether presence or absence of the brachial plexus injury in patients with first rib fracture. PMID- 2246531 TI - [Surgical treatment of upper mediastinum involvement following thyroid cancer surgery]. AB - Four cases with mediastinal nodal involvements after surgery for thyroid cancer were treated by tumor extirpation and mediastinal lymph nodes dissection. The removal were performed via the median sternotomy in three cases and partial resection of the clavicle in one case. The transsternal approach made it possible to remove the tumor with mediastinal lymph nodes safely and easily. It is generally sufficient to carry out dissection as far as the brachiocephalic vein. However, mediastinal nodal involvements extending below the brachiocephalic vein were seen in one of 4 cases. All patients are alive, including 2 cases with lung metastases. Initial aggressive surgical treatment of mediastinal recurrence is important for preventing the obstruction of the trachea or large vessels. PMID- 2246532 TI - [Congenital atresia of the left main coronary artery ostium--a case suffering from ventricular tachycardia]. AB - A case of congenital atresia of the left main coronary ostium suffering from ventricular tachycardia underwent coronary artery bypass operation. The patient was 17 years old boy. When he was 9 years old he visited our department for the purpose of examining cardiac disease. The diagnostic impression was mitral regurgitation. At 16 years old he suddenly complained tachycardia during exercise. He admitted to our hospital and the tachycardia was proved to be ventricular tachycardia. Left ventriculogram demonstrated a small range of akinesis at the left ventricular apex. And coronary cineangiogram revealed atresia of the left main coronary artery. The left coronary artery was perfused with collateral circulations from right coronary artery. Electrophysiological study was performed. The ventricular tachycardia could be reproducibly initiated and terminated by programmed stimulation. The catheter endocardial mapping was also performed. The source of ventricular tachycardia was supposed to be at the left ventricular apex. At 18 years old coronary artery bypass operation was performed. Internal mammary artery graft was placed to the left anterior descending artery and a saphenous vein graft was placed from the ascending aorta to the left circumflex artery. A small size of myocardial infarction was recognized at the left ventricular apex. And epicardial mapping revealed that the source of arrhythmia was the same region as the myocardial infarction was recognized. Endocardial resection or cryoablation was not performed. Post operative study was performed 8 months after surgery. The graft flow of the internal mammary artery to the left anterior descending artery was not sufficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246533 TI - [A case report of traumatic transection of the aortic arch]. AB - A 16-year-old male, who sustained a blunt chest trauma in a traffic accident, was brought into the emergency room in an unconscious state, with an initial systolic blood pressure of 80 mmHg. He was found to have multiple fractures and a flail chest. The initial roentgenogram of the chest showed widening of the mediastinum. An emergency aortogram demonstrated intimal flap and aneurysmal dilatation of the aortic arch. Because of a coexisting severe contusion of the lung, operation was postponed until 15 days after admission. He was successfully treated by direct repair under profound hypothermia and circulatory arrest, which was induced by surface cooling in combination with ECC. Postoperatively he did well and 23 days after the operation, surgical repair of femoral and humeral fractures was performed by orthopedists. PMID- 2246534 TI - [Left ventricular myxoma with mucocutaneous myxoid tumors--a case report]. AB - A surgical treatment of left ventricular myxoma arising from the anterior wall of the left ventricle is reported. A 32 year old man with a history of transient syncopal attack had an echocardiographic diagnosis of left ventricular myxoma. He previously had had myxoid tumors excised from the nose and from the posterior part of the left thigh. Cardiac surgery was performed under extracorporeal circulation on December 20, 1989. A friable, gelatinous 5 cm long myxoma with a diameter of 3 cm was excised from the left ventricule. The postoperative course was uneventful. The clinical characteristics in all the reported cases of cardiac myxomas with associated myxoid tumors of the skin are reviewed. Cardiac myxomas in patients with mucocutaneous myxoid tumors have an atypical biological behavior with early development of myxomas, atypical location, multiple tumors and high rate of recurrent myxomas. PMID- 2246535 TI - [Left ventricular-right atrial communication following mitral valve replacement]. AB - A case of an acquired left ventricular-right atrial communication complicating Omnicarbon replacement of a severe calcified mitral valve in the area of the posteromedial commissure is reported. The intricate relationships of the membranous atrioventricular septum to the mitral valve and the tricuspid valve predispose to the creation of an iatrogenic left ventricular-right atrial fistula when aggressive debridement of extensive valvular calcification is performed. Emphasis is placed on the diagnosis, and immediate surgical repair is advocated as soon as this complication is discovered. PMID- 2246536 TI - [A case report of Bochdalek's hernia with volvulus of the stomach in an adult]. AB - We report a rare case of Bochdalekhs hernia, congenital posterolateral diaphragmatic hernia with mesenterioaxia volvulus of the stomach, in an adult. A 23-year-old man suddenly felt severe pain in his left chest after drinking beer. Roentgenologic examination of the chest showed air above the left diaphragm, and the mediastinum was displaced to the right. Upper gastrointestinal series revealed mesenterioaxial volvulus of the stomach in which the pylorus was displaced to the left. Thoracotomy through the left seventh intercostal space was performed. The stomach, colon, spleen and greater omentum were displaced into the left thoracic cavity. After reduction of the herniated viscera, a defect measuring 10 X 4 cm, in the posterolateral part of the diaphragm, was closed with double interrupted Tevdek sutures. Three months later, he was asymptomatic and his chest roentgenogram was normal. PMID- 2246537 TI - [A case of malignant mesothelioma of the pleura]. AB - An operative case of malignant localized mesothelioma of the pleura, a 63-year old male, came to our clinic with the chief complaint of hemosputa. On suspicion of lung tumor, right upper lobectomy and lymph node cleaning were performed. The tumor was embedded in the lung; there was no infiltration into the chest wall. After the operation, radiotherapy was added but tumor recurrence occurred in the 5th month, and the patient died 7 months after surgery. From the form of the recurrence it was considered a diffuse-type transition case. The prognosis of this disease is known to be poor, but since there have also been cases of long survival, cases of resection are studied in Japan. Based on macroscopic tumor findings, cases of occurrence in the visceral pleura have poor prognosis if embedded in the lung, while cases of occurrence in the parietal pleura have varied prognoses, but the differentiation line is yet unclear. Among six cases of diffuse-type transition, including this case, five cases were of the histological type which included the epithelial component. Further study of these cases is necessary in the near future. PMID- 2246538 TI - [Three cases of familial dissecting aortic aneurysm]. AB - The occurrence of aortic dissection in 2 or more family members is rare. Such occurred, however, in the brothers and elder sister described herein. Case 1: A 54-year-old male had chronic Type I dissecting aortic aneurysm with severe aortic insufficiency and abdominal aortic aneurysm. Case 2: A 57-year-old female had chronic Type II dissecting aortic aneurysm with severe aortic insufficiency. Case 3: A 49-year-old male had chronic Type IIb dissecting aortic aneurysm. Two cases (Case 1 & 3) of them had surgical interventions. The histology showed cystic medial necrosis of aorta. Neither of these 3 patients or other family members had skeletal or ocular features of the Marfan syndrome. The metacarpal indices of them were well within normal. Their parents are cousins. It is, therefore, likely that the occurrence of dissecting aneurysm in the above three cases was due to an underlying hereditary disease. Thus familial dissecting aneurysm is suggested. PMID- 2246539 TI - [A case of anomalous right pulmonary venous drainage to high segment of superior vena cava with intact atrial septum--surgical repair by cavoatrioplasty avoiding injury to the sinoatrial node and its feeding artery]. AB - Surgical repair of anomalous right pulmonary venous drainage to the high segment of the superior vena cava (SVC) with intact atrial septum in a 5-year-old girl by cavoatrioplasty avoiding injury to the sinoatrial (SA) node and its feeding artery is described. The procedure was composed of #1: an oblique incision at the anterior wall of SVC above the anomalous right pulmonary veins (ARPVs) and closure of the lower end of the SVC, making the lower segment of SVC the ARPV channel, #2: a fan-shaped incision at the base of the right atrial (RA) appendage and suturing the cephalad flap over a created atrial septal defect, diverting the ARPV flow through the SVC into the left atrium, and #3: reconstruction of continuity between the cephalad end of the SVC and the RA by suturing the RA appendage flap over the lower segment of SVC. Pulmonary valvotomy was also done for concomitant pulmonary stenosis. Postoperative course of the patient was excellent, with constant normal sinus rhythm. Angiography one month after operation showed no stenosis of the SVC and pulmonary venous pathways. The method reported here was considered to have following advantages: It employs simple and short incisions, avoids injury to the SA node its feeding artery, and achieves wide and nonobstructive pathways of both SVC and pulmonary venous return without using foreign material. PMID- 2246540 TI - [A case report of fibromatosis originating from the right anterior scalene muscle]. AB - Fibromatosis is rare and locally invasive tumor arising from musculoaponeurotic tissue, and also has a high postoperative recurrence rate. So, we must perform wide resection of the tumor and surrounding tissue. A case of fibromatosis originating from the right anterior scalene muscle was reported. A 31-year-old female in whom cervical fibromatosis had been pointed out by her home doctor, was referred to our hospital for treatment. CT scan, MRI and angiography showed that the tumor developed from the cervical lesion to the upper thoracic and invaded the right subclavian artery. The tumor originating from right anterior scalene muscle was found at operation. The combined resection consisted of the right anterior salene muscle with tumor, phrenic nerve, subclavian artery and vein, and chest, well including the first and second rib and clavicular bone, because of wide invasion of tumor to surrounding organs. Reconstruction of the subclavian artery and vein was performed by PTFE vascular prostheses. The postoperative course was uneventful, she is now in good health 8 months after operation with good blood flow via the reconstructed vessels confirmed by angiography, without any sign of recurrence. PMID- 2246541 TI - [A rare case of congenital tricuspid stenosis treated with modified Fontan operation]. AB - A rare case of congenital tricuspid stenosis treated with modified Fontan operation was reported. The patient was 13 years old boy and his chief complaint was cyanosis. Cyanosis appeared in his neonatal period and squatting developed in his childhood. He underwent Blalock's shunt operation at 5 years of age. His exercise tolerance was limited at the admission for the radical operation. Angiocardiography showed the annular stenosis of tricuspid valve and the moderate hypoplasia of right ventricle. The right ventricular volume was 56 ml (equivalent to 35% of the normally expected right ventricular volume) and the diameter of tricuspid annulus was 13 mm (equivalent to 58% of the normally expected diameter). Atrial septal defect was associated with but pulmonary stenosis did not exist. His left ventricular function was good and pulmonary vascular resistance was not raised. A diagnosis of tricuspid stenosis was made and Fontan's repair was considered to be possible for his correction. Operative findings showed normal architecture of tricuspid valve with the three leaflets but tricuspid annulus was narrow. Tricuspid valve stenosis was considered to be caused by the hypoplasia of tricuspid ring and surgical dilatation was found to be difficult. Therefore, modified Fontan operation (RA-RV connection) was performed. His cyanosis disappeared and exercise tolerance was improved after the operation. Cardiac catheterization and angiocardiography were performed 8 months and 28 months after the operation. His righ ventricular volume was increased to 123 ml (equivalent to 57% of the normally expected volume) followed by RA-RV connection. PMID- 2246542 TI - [A case report of definitive repair for pulmonary atresia and intact ventricular septum associated with aortic valve regurgitation]. AB - A successful definitive repair for a 10-year-old girl with pulmonary atresia and intact ventricular septum (PA.IVS) associated with aortic valve regurgitation is described. The Fontan type repair was not indicated in this case because of the left ventricular dysfunction due to aortic valve regurgitation and inadequate size of the pulmonary artery. Therefore, right ventricular outflow tract reconstruction, Glen shunt and aortic valve replacement were performed despite severe hypoplastic right ventricle (RVEDVI; 33% of normal) and restrictive tricuspid valve (TVD; 48% of normal). Postoperatively, good result was obtained. There is general agreement that biventricular repair could be safely performed using Glenn shunt, when RVEDVI is above 40% of normal and TVD is above 50% of normal in a patient with PA.IVS. Moreover recently including our case, several successful repairs for PA.IVS with more hypoplastic right ventricle and tricuspid valve have been reported. So it is suggested that the right ventricular outflow tract reconstruction and Glenn shunt can be reliably applied for PA.IVS with more hypoplastic right ventricle and more restrictive tricuspid valve. To our knowledge, this is the first successful report of definitive repair (right ventricular outflow tract reconstruction, Glenn shunt and AVR) for PA.IVS associated with AR. PMID- 2246543 TI - [A surgically treated case of partial anomalous pulmonary venous connection to the right atrium, diagnosed by magnetic resonance imaging]. AB - We report a successful surgical repair of a 33-year-old male with partial anomalous pulmonary venous connection (PAPVC) to the right atrium and pulmonary valve stenosis. This case was diagnosed using Magnetic Resonance Imaging (MRI). The findings of MRI clearly showed an abnormal development of the atrial septum far to the left, and the right lower pulmonary vein connected to the right atrium. An embryologic explanation of PAPVC can be provided in many cases by persistent communication between pulmonary veins and systemic veins. However, the MRI findings of this case support the suggestion of Neill that an abnormal development of the atrial septum far to the left provides an embryologic explanation for PAPVC to the right atrium. Preoperative MRI study of PAPVC to the right atrium prove to be of great value in preventing accidental over-cutting of the posterior atrial wall during surgical correction. PMID- 2246544 TI - [Non-Hodgkin's lymphoma arising from the wall of old tuberculous empyema--a surgical case report]. AB - A 71-year-old male underwent therapeutic pneumothorax for left pulmonary tuberculosis 42 years ago. He visited our hospital in February 1988 with a complaint of hemosputum. In October, cytology of sputum revealed malignant cells, and the patient was admitted to our hospital for further examination. Because malignant cells were found by the left bronchial lavage, pan-pleuropneumonectomy was performed on January 12, 1989 under the diagnosis of left lung cancer. The tumor was partially left unremoved. Histological diagnosis was diffuse large cell type, B cell non-Hodgkin's lymphoma. Postoperatively, 2 courses of cyclophosphamide, adriamycin, vincristine, prednisone, etoposide (CHOP and VP-16) therapy were performed. However, the patient died of respiratory insufficiency on the 125th postoperative day. Recently, cases of malignant lymphoma involving the pleura after the old tuberculous empyema and therapeutic pneumothorax have been increased. Therefore, prompt diagnosis and treatment are recommended when tumor shadow is suspected as a result of imaging examination. PMID- 2246545 TI - [Coronary artery bypass in dextrocardia with situs inversus totalis--a case report]. AB - A 71-year-old woman was admitted to our hospital by ambulance, because of right chest pain and hypotension. Chest X-ray and standard 12-lead ECG showed mirror image dextrocardia with situs inversus totalis. ECG with right-left reversal of all leads showed acute inferior myocardial infarction. The patient underwent coronary bypass surgery due to postinfarction angina, and she is now doing well 2 years following the operation. Mirror-image dextrocardia with situs inversus totalis is very unusual. But the patients are believed to have normal longevity, and presumably have an incidence of atherosclerotic coronary artery disease similar to the general population. To our knowledge, this is the first case of coronary bypass surgery on a patient with mirror-image dextrocardia in Japan. PMID- 2246546 TI - [Successful correction of truncal valve regurgitation and conduit obstruction after previous Rastelli operation for truncus arteriosus (type I)]. AB - A 9-year-old boy had a successful surgical correction of truncal valve regurgitation and obstruction of extracardiac conduit which ensued previous Rastelli operation. He underwent Rastelli operation at the age of 10 months with the diagnosis of truncus arteriosus (Collet & Edwards Type I). At the age of 8 years, he was admitted because of slow weight gain and cardiomegaly (CTR 64%). Cardiac catheterization showed elevated RV pressure, increased pressure gradient across the conduit and severe truncal valve regurgitation. The extracardiac conduit was replaced with a 22 mm Hancock valved conduit and the truncal valve with 23 mm St. Jude Medical aortic valve. Postoperative catheterization revealed a normal RV pressure, only slight pressure gradient across the conduit and no truncal valve regurgitation. He is doing quite well 2 years after the operation. PMID- 2246547 TI - [A case of tracheoesophageal fistula in Behcet's disease repaired with pericardial patch and gastric roll]. AB - A 23-year-old man suffering from Behcet's disease developed a tracheoesophageal fistula. Subtotal esophagus was stripped and replaced with a gastric tube along greater curvature. The defect of membranous portion of the trachea (2 X 1 cm) was closed with a pedicled pericardial patch and covered with omentum. Transient postoperative recurrent nerve palsy was recovered in about 2 months. He is going well without any significant complaints. He received steroid hormone administration and platelets transfusion because of complicated ITP (Idiopathic Thrombocytopenic Purpura). PMID- 2246548 TI - The future of medical journalism. PMID- 2246549 TI - Landmark Articles and Citation Classics in the Journal of Laboratory and Clinical Medicine. PMID- 2246550 TI - The unfolding saga of blood irradiation. PMID- 2246551 TI - Resistance of platelet proteins to effects of ionizing radiation. AB - Gamma irradiation of blood components prevents lymphocyte-induced graft-versus host disease after transfusion in immunocompromised individuals. In this report we demonstrate the resistance of blood platelet proteins to gamma radiation induced protein cleavage and aggregate formation when platelet concentrates were treated with a dose of 5000 rad. Results of one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total platelet protein and cytoskeletal protein preparations indicate that platelet proteins are neither cleaved nor cross-linked under these conditions of irradiation. These results support those of a previous study that documented the lack of any adverse effect of 5000 rad gamma radiation on in vitro platelet properties. PMID- 2246552 TI - A constitutive antibody in normal human serum directed against rabbit bone marrow cells: lack in parturients, neonates, and hematologic disorders. AB - Normal human serum effectively inhibits a bioassay for erythropoietin based on DNA synthesis by rabbit erythroid precursors. This heat-sensitive inhibitory activity is readily lost on dilution of serum, revealing the presence of erythropoietin-potentiating activity. Inhibitory activity is caused by a rapid cytotoxic effect on rabbit bone marrow cells; mouse cells are less sensitive. Cytotoxic activity is removed from serum by adsorption to protein A, is not expressed at 4 degrees C, and is neutralized by anti-C3c complement antibody. Cytotoxicity is inhibited by EGTA; the effect of EGTA is reversed by addition of Ca2+ ions. These findings show that cytotoxicity is exerted through an antibody via the classical pathway of complement-dependent cell lysis. Although serum from healthy, adult human donors consistently contains cytotoxic activity, no such activity is observed in most serum samples from neonates, parturients, and patients with severe anemia. Patients with polycythemia or chronic renal failure occasionally lack cytotoxic activity in their serum. Serum samples lacking cytotoxic activity were found to be deficient in the antibody component in 34 out of 35 cases examined. These results show that an antibody directed against rabbit cells is constitutively present in normal human serum but is absent in a number of pathologic situations as well as being absent in neonates and parturients. PMID- 2246553 TI - Method for establishing serum ferritin reference values depending on sex and age. AB - A method is described for the establishment of reference values for serum ferritin depending on sex and age. The results obtained in a stratified random sample of 353 healthy individuals from the Portuguese population revealed that 23% of the variation observed on serum ferritin values was related to sex differences and 6% of the variation was explained by age differences. Furthermore, the effect of age was different in both sexes: serum ferritin values increase with age in females over 40 years and in males under 40. The minimum and maximum reference values were established for the different subgroups of subjects as follows: for females under 40 years and males over 40, reference values were considered as the 2.5 and 97.5 percentiles from the adjusted lognormal distribution; for females over 40 years and males under 40, reference values were considered as the exponential transformation of the upper and lower limits of the 95% prediction intervals for the log of serum ferritin for each particular age point. PMID- 2246554 TI - Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting. AB - Serum samples from 398 individuals (270 whites and 128 blacks) exhibiting quantitatively normal amounts of five typically seen fractions (albumin, alpha 1 globulin, alpha 2-globulin, beta-globulin, and gamma-globulin) in serum protein electrophoresis and showing no evidence of multiple myeloma, other immunoproliferative diseases, or any of the other diseases known to produce monoclonal proteins were tested for monoclonal gammopathy of undetermined significance (MGUS) by immunofixation electrophoresis. No individual in the study had a serum protein electrophoresis pattern suggestive of monoclonal protein gammopathy. Except for one 37-year-old woman, all subjects were men. Subjects were divided into seven age groups: 20 to 29 years (I), 30 to 39 years (II), 40 to 49 years (III), 50 to 59 years (IV), 60 to 69 years (V), 70 to 79 years (VI), and all over 79 years (VII) of age. Considering all subjects in a given race, blacks had two times (14.8%) higher incidence of MGUS than whites (7.8%); this difference was statistically significant. An increased incidence of MGUS in blacks when compared with whites prevailed in each age group, and the difference was statistically significant in all age groups except group II. No MGUS was found in groups I and III in either race. Both races showed a threefold increase in incidence of MGUS from group II to group VII. No routine laboratory test such as erythrocyte sedimentation rate in subjects with MGUS was significantly different than that in age- and race-matched individuals without MGUS. These results show that the incidence of MGUS is higher in the group (blacks) also known to have a higher prevalence of multiple myeloma. PMID- 2246555 TI - The effect of sodium on hemodynamic changes during coronary angiography with nonionic contrast media. AB - To investigate the effect of sodium on cardiac hemodynamics, sodium chloride was added to nonionic contrast media to a 0.9% concentration and was compared with the standard media iohexol, iopamidol, and ioversol. Left coronary angiography was performed in 10 closed-chest, atrial-paced dogs with 10 ml injections of each preparation in a randomized and blinded fashion. The maximum changes in left ventricular systolic pressure, mean aortic pressure, left ventricular and diastolic pressure, and maximal rise of left ventricular pressure were measured. The left ventricular systolic pressure and mean aortic pressure decreased by 17 +/- 7 mm Hg and by 12 +/- 5 mm Hg with iohexol plus 0.9% NaCl, but only by 5 +/- 4 mm Hg and by 4 +/- 3 mm Hg with iohexol alone (p less than 0.001). The left ventricular and end diastolic pressure increased by 2.2 +/- 0.6 mm Hg with iohexol plus 0.9% NaCl, but did not change with iohexol alone (p less than 0.001). Left ventricular dp/dt decreased by 204 +/- 161 mm Hg/sec with iohexol plus 0.9% NaCl but increased by 392 +/- 122 mm Hg/sec with iohexol alone (p less than 0.001). Similar results were obtained from experiments with iopamidol versus iopamidol plus 0.9% NaCl and ioversol versus ioversol plus 0.9% NaCl. Ioversol plus 5% dextrose or ioversol plus 2.1% choline chloride (isomolar to ioversol plus 0.9% NaCl) produced a significant increase in left ventricular systolic pressure and left ventricular dp/dt (versus ioversol plus 0.9% NaCl, p less than 0.001). Thus, sodium, but not the osmolality or chloride, contributed to the negative inotropic effect of the contrast media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246556 TI - Effects of prostaglandin E1 on platelet attenuation of oxidant-induced edema in isolated rabbit lungs. AB - Numerous studies suggest that platelets may contribute to preservation of normal endothelial cell permeability in models of lung injury. We have previously shown that washed human platelets prevent xanthine oxidase-induced edema in the isolated perfused lung and that protective mechanisms depend on the platelet glutathione redox cycle. It is uncertain, however, whether platelets preserve endothelial function by reducing toxic oxygen metabolites or by aggregating and releasing endothelial cell supportive factors-an activity that may require the glutathione redox cycle. In this study, we present data demonstrating that platelet prevention of oxidant lung injury occurs independent of platelet aggregation and release. Isolated rabbit lungs perfused with a cell-free medium were instilled with purine (2 mmol/L) and xanthine oxidase (0.003 U/ml) to generate oxidant lung edema. The infusion of washed human platelets (1 x 10(10) cells) prevented lung edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, and lung histology. Incubation of platelets with prostaglandin E1 (PGE1), a potent inhibitor of platelet aggregation and release, did not inhibit platelet attenuation of lung edema. Additionally, with the instillation of PGE1 into the perfusate to further inhibit platelet aggregation, no prevention of lung protection by PGE1-treated platelets was seen when these results were compared with those from studies in which lungs were infused with xanthine oxidase and PGE1. Aggregometry studies documented that the inhibitory effect of PGE1 on platelet aggregation persisted for up to 60 minutes, which was the duration of the isolated lung protocol. We conclude that platelet aggregation and release of platelet factors is not required for platelet attenuation of oxidant lung edema. PMID- 2246557 TI - Identification and isolation of a phospholipase A2 activating protein in human rheumatoid arthritis synovial fluid: induction of eicosanoid synthesis and an inflammatory response in joints injected in vivo. AB - Eicosanoids are important mediators of the destructive arthropathy observed in rheumatoid arthritis. The rate-limiting step in the eicosanoid synthesis pathway is the availability of free arachidonic acid. The phospholipase enzymes release arachidonic acid from membrane phospholipids and thus play an important role in the regulation of eicosanoid production. We have previously demonstrated enhanced phospholipase A2 and C enzyme activities in cells from patients with rheumatoid arthritis and have also described a phospholipase A2 activating protein (PLAP) in mammalian cell lines. In an attempt to determine the biochemical basis of enhanced phospholipase A2 activity found in patients with inflammatory joint disease, we examined synovial fluid from patients with rheumatoid arthritis for PLAP. To determine whether PLAP was specific for rheumatoid disease, we assayed specimens from patients with other arthropathies. Histologic examination of rheumatoid joint tissue, with the use of immunohistochemical techniques, demonstrated high concentration of PLAP in monocytes, macrophages, chondrocytes, vascular smooth muscle, and endothelial cells. Human PLAP could be biochemically isolated from synovial fluid from patients with rheumatoid arthritis and was found to be similar to PLAP previously isolated from murine and bovine sources. To determine whether PLAP could directly mediate any aspect of inflammatory disease, purified PLAP was injected into rabbit knee joints. This resulted in an acute inflammatory arthritis with synovial cell proliferation and synovial fluid leukocytosis. Purified PLAP also induced eicosanoid formation both in vivo and in vitro. With enzyme-linked immunosorbent assays, we found more PLAP in synovial fluid specimens from patients with rheumatoid arthritis compared with samples from patients with other inflammatory arthropathies as well as osteoarthritis, a noninflammatory arthropathy. These data suggest that PLAP may be responsible, at least in part, for some aspects of the destructive inflammatory arthropathy that is observed in patients with rheumatoid arthritis. PMID- 2246559 TI - Production of thrombi on intact endothelium by use of antiheparin agents in vivo. AB - It had been suggested that antithrombin activity on the surface of intact endothelial cells may play a role in inhibiting platelet adhesion and thrombus formation. The antithrombin activity may be due to thrombomodulin or to activation of antithrombin III by glycosaminoglycans or thrombomodulin, or possibly a combination of these. This inhibitory activity has been shown to be affected by such antiheparin agents as protamine, hexadimethrine bromide (Polybrene; Aldrich Chemical Co., Milwaukee, Wis.) and platelet factor 4, as well as by such enzymes as heparinase and heparitinase. We have used a hamster cheek pouch preparation to observe thrombus formation in vivo in a normal vascular flow, to determine whether the production of thrombi by thrombin can be enhanced by antiheparin agents. After intra-arterial injection or topical application of protamine or hexadimethrine bromide, platelet adhesion and thrombus formation on intact arteriolar endothelium was produced by a dose of thrombin, which when injected alone had no effect. No thrombi were found in venules or capillaries. Injection of heparin before or after the antiheparin agents necessitated a larger dose to enhance the action of thrombin. On electron microscopy the thrombi were found to consist primarily of platelets adherent to an intact endothelium. The possible clinical implications of these observations are discussed. PMID- 2246558 TI - Negative screening for sickle cell diseases with a monoclonal immunoassay on newborn blood eluted from filter paper. AB - The most common method of blood sample collection for neonatal screening programs for inherited diseases-blood spots on filter paper--is poorly suited for screening of sickle cell diseases by conventional assays because of the denaturing effects of this medium on hemoglobins that affect their electrophoretic identifications. The monoclonal antibody beta (6)-1 specifically recognizes the hemoglobin A beta-chain residue 6 (glutamic acid), that is, the normal counterpart of hemoglobins S and C, and this recognition is unaffected by changes in hemoglobins induced by filter paper storage. The beta (6)-1 immunoassay analysis of 67 prescreened samples extracted from filter paper permitted unambiguous group identification, by virtue of nonreactivity, of the pathologic sickle cell disease phenotypes SS (sickle cell anemia) and SC (sickle cell-hemoglobin C disease), along with the homozygous hemoglobin C phenotype (hemoglobin CC disease). Other phenotypes identified by beta (6)-1 nonreactivity would include S-beta(0) thalassemia, C-beta (0) thalassemia, and beta(0) thalassemia (Cooley's anemia). As systems for collecting newborn blood specimens on filter paper and their transmittal to centralized laboratories are already established in many states, this assay for sickle cell and hemoglobin C diseases could rapidly be combined with other mass screening programs for inborn errors of metabolism. PMID- 2246560 TI - Rheologic properties of mixed hemoglobin gels: deoxyhemoglobins S and A. AB - To obtain new information concerning the behaviors, and in turn the structures, of gels formed from mixtures of S and A hemoglobins, their physical properties have been characterized by stress relaxation with a rotational rheometer. The variables manipulated were (1) initial total hemoglobin concentration, (2) mole fraction of hemoglobin S present in the mixture, (3) hemoglobin A as intact tetramer only or as both tetramer and hybridized hemoglobin AS, (4) annealing time, (5) shear history, (6) temperature, and (7) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin SA gels were less solid than those of pure S of similar initial hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by shear history, annealing time, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin SA gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. The presence of hemoglobin A with hemoglobin S results in polymers and gels that differ from those found in pure hemoglobin S. Pathophysiologic implications of these findings for sickle cell disorders are proposed. PMID- 2246561 TI - Distribution of primaquine in human blood: drug-binding to alpha 1-glycoprotein. AB - To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2 butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist. PMID- 2246562 TI - Splenic thrombopoiesis after bone marrow ablation with radiostrontium: a murine model. AB - Murine platelet production is normally supported by high-ploidy bone marrow megakaryocytes without significant contribution from splenic megakaryocytes with predominantly low-ploidy levels. We produced sustained bone marrow ablation using radiostrontium, and examined the processes by which splenic platelet production is initiated and maintained in the absence of bone marrow function. Bone marrow hematopoiesis, measured by total nucleated cell number and viability, megakaryocyte colony-forming cells, and granulocyte-macrophage colony-forming cells, was rapidly ablated in mice by using yttrium 90-free strontium 90. Platelet count declined from normal (1224 x 10(3)/microliters) to a nadir (98 x 10(3)/microliters) 11 days after 90Sr, and then rose to a stable level (705 x 10(3)/microliters) on days 20 through 115. Peripheral leukocyte concentration decreased rapidly and remained below 25% of normal in contrast to hemoglobin levels, which were minimally lowered. Mean spleen weight rose rapidly after 90Sr to 66% above normal. Splenic megakaryocyte frequency, measured by two-color fluorescence-activated flow cytometry, rose from basal levels (0.09% +/- 0.06%) to 0.15% +/- 0.07% (p less than 0.001), total spleen nucleated cells fell to 71% of normal, and the absolute number of spleen megakaryocytes was unchanged. Total spleen megakaryocyte colony-forming cells were not significantly increased above normal whereas total spleen granulocyte-macrophage colony-forming cells increased abruptly after day 13 to 10 times normal levels. Splenectomy after hematopoietic recovery from 90Sr bone marrow ablation resulted in a rapid decline of platelet levels, followed by death. Although the spleen became the sole site of platelet production, the splenic megakaryocyte ploidy distribution was only minimally changed from normal, and the modal ploidy class remained 2N. In contrast to experimental thrombocytopenia in mice with intact bone marrow, in which megakaryocyte ploidy is increased, thrombocytopenia associated with sustained bone marrow ablation does not result in upward regulation of splenic megakaryocyte ploidy as a compensatory mechanism. PMID- 2246563 TI - Clinical and experimental. The natural history of the renal manifestations of systemic lupus erythematosus. 1964. PMID- 2246564 TI - The history of Rush Medical College. PMID- 2246565 TI - Pride in medicine. PMID- 2246566 TI - Health Access America: an update. PMID- 2246568 TI - Wegener's granulomatosis presenting as subglottic stenosis. AB - One of the rarest diseases associated with upper airway obstruction in adults is subglottic stenosis from the necrotizing vasculitis of Wegener's granulomatosis. Early recognition and treatment of this potentially fatal syndrome is necessary to insure long-term survival. PMID- 2246567 TI - Group C streptococcal meningitis with favorable recovery. A case report. AB - Group C beta-hemolytic Streptococcus, though an uncommon cause of meningitis in adults, often leads to the demise of the patient or a prolonged hospital course, usually with residual neurologic impairment. We report a case of group C streptococcal meningitis in a previously healthy young adult, with rapid and complete recovery following early initiation of IV penicillin therapy. PMID- 2246569 TI - Rural medicine. PMID- 2246570 TI - The fun days are gone. PMID- 2246571 TI - Preston P. Nunnelley, MD. KMA's president 1990-91. PMID- 2246572 TI - The use of nonsteroidal anti-inflammatory agents. PMID- 2246573 TI - A long term view of myringoplasty in children. AB - Fifty-nine type 1 tympanoplasties in children under 14 years of age were assessed by recall to a special follow-up clinic up to 15 years post-operatively. Overall 78 per cent of tympanic membranes were found to be intact with a late failure of grafts noted in 6 per cent of cases. An improvement in the audiological threshold was found in 51 per cent, 24 per cent were unchanged, the remaining 25 per cent suffered a deterioration which was seen both immediately post-operatively and thereafter until reviewed in the special clinic. The age at operation, size of the perforation, grade of surgeon carrying out the operation and prior adenoidectomy had no statistically significant influence on the success rate or the audiological outcome. Revision procedures achieved similar graft take rates to the initial procedures but fared worse audiologically. We conclude that in the majority the operation was successful but hearing gain was not as good as expected and subject to late deterioration. A long term follow-up is important to detect this and other complications. PMID- 2246574 TI - The Dansac mini cap: a new method of waterproof ear protection. AB - The best method of providing waterproof protection for susceptible ears remains a contentious issue. Many evaluations have concentrated on the efficacy of intraluminal plugs in normal or model ears. We describe a new method, using a jejunostomy shower cap (Dansac mini cap), which avoids intraluminal insertion. This method has proved useful in some patients who have failed to avoid repeated otorrhoea after water exposure despite using a wide range of intraluminal ear plugs. The shower caps are best avoided in children because of teasing. PMID- 2246575 TI - Primary intratemporal tumours of the facial nerve: diagnosis and treatment. AB - Benign primary tumours of the facial nerve are uncommon. A slowly progressive facial palsy should be considered the result of a nerve tumour until proven otherwise. Improvements in diagnostic imaging techniques of the temporal bone have increased the possibility of a correct pre-operative diagnosis but facial nerve tumours remain a frequently ignored or misdiagnosed entity as a consequence of their subtle and protean clinical manifestations. A series of 12 cases of primary facial nerve tumours is presented. The clinical features, diagnostic modalities and treatment are discussed in relation to a review of the literature. PMID- 2246576 TI - The effect of rifampicin on rhinoscleroma: an electron microscopic study. AB - Twenty-five cases suffering from rhinoscleroma were divided into two groups. The first group consisted of 15 patients treated with rifampicin systemically. The other group consisted of 10 patients treated locally with rifampicin in the form of ointment. Electron microscopic study of the pathological changes in the lesions showed that rifampicin is highly effective both systemically and locally in the treatment of rhinoscleroma. PMID- 2246577 TI - Radiological diagnosis of aspirated foreign bodies in children: review of 343 cases. AB - In our series of 400 Chinese children with foreign body aspiration (FBA), 343 cases were evaluated by fluoroscopy and/or plain chest X-rays before endoscopic removal of the foreign bodies. The majority of the foreign bodies (FBs) were organic (378/400, 94.5 per cent). The results showed that mainstem bronchial foreign bodies were diagnosed correctly in 68 per cent of cases compared with 65 per cent correct diagnoses with segmental bronchial foreign bodies, but only 22 per cent correct diagnoses with tracheal, and 0 per cent correct diagnosis in those with laryngeal foreign bodies. Eighty per cent (32/40) of the children with laryngotracheal FBs had normal X-ray findings, whereas 67.7 per cent (205/303) of the children with bronchial FBs had abnormal chest X-ray findings. The most common positive radiological signs in the children with tracheobronchial FBs were obstructive emphysema (131/213, 62 per cent) and mediastinal shift (117/213, 55 per cent). The incidence of major complications was related not only to the size of the foreign body and its location but also the duration since aspiration. The most common types of bronchial obstructions by airway FBs are discussed. PMID- 2246578 TI - Monomorphic adenomas of the major salivary glands: clinicopathological study of 44 cases. AB - We report 44 cases of monomorphic adenoma (MA) of the major salivary glands observed during the years 1979-1989. All of these tumours were reviewed and classified on the basis of the World Health Organisation (WHO) criteria. Histological type, site, sex and age were considered. 34 cases of adenolymphoma were observed, all of them located in the parotid glands; 10 MA without lymphoid stroma were located in both parotid and submandibular glands. Distinctive histological and clinico-pathological features of the latter group of tumours are discussed, as well as the diagnostic criteria in distinguishing these tumours from pleomorphic adenoma and adenoid-cystic carcinoma. PMID- 2246579 TI - Tumefactive fibroinflammatory lesions of the head and neck. AB - The term 'tumefactive fibroinflammatory lesion' has been used to describe a fibrosclerosing disorder which has a locally destructive nature but is characterized by a benign histological appearance. We report five patients, over a five year period, with such a lesion. The clinical behaviour and surgical findings suggest the lesion to be an invasive malignancy. However, the histological appearance of an admixture of chronic inflammatory cells and fibrosis is consistent with a benign condition. We recommend surgical excision of the lesion as the mainstay of treatment; other studies report the use of steroids and radiotherapy. PMID- 2246580 TI - Role of routine fluid replacement in children undergoing tonsillectomy. AB - It has been suggested that children undergoing tonsillectomy would benefit from an intravenous infusion, to counteract the period of pre-operative fasting combined with the blood loss at operation. A prospective study of 50 children undergoing tonsillectomy was undertaken. The children were randomly allocated into two groups, one to receive an infusion and a control group. There were no significant differences between the two groups, although the children with an infusion had a longer mean post-operative stay. There would seem to be no role for routine intravenous fluid replacement in children undergoing uncomplicated tonsillectomy. PMID- 2246581 TI - Osteoma of the middle ear. AB - Osteomas involving the middle ear and causing a functional disturbance are rare. We report a case of a patient with an osteoma arising from the lateral semicircular canal. The main symptom was vertigo and to halt this the defect of the canal was obliterated with a bone chip and fibrin glue after removal of the tumour. PMID- 2246582 TI - Hearing loss due to cranio-metaphysial dysplasia. AB - Craniometaphysial dysplasia is a rare cause of conductive hearing loss. It is a genetic disorder of bone due to decreased osteoclastic activity in the endosteal and periosteal regions of craniofacial and long bones. The characteristic temporal bone abnormalities are attic fixation, abnormally shaped ossicles and obliterated foramina ovale. Computerised tomography is helpful in predicting operative findings; surgery should be reserved for those with a severe hearing loss. PMID- 2246583 TI - Auro-nasopharyngeal polyp and cholesteatoma. AB - We report the association of an auronasopharyngeal polyp arising in a congenitally abnormal middle ear and Eustachian tube. Subsequently, ten years after removal of the polyp and insertion of a ventilation tube, there was recurrence of the polyp in association with cholesteatoma of the middle ear. PMID- 2246584 TI - Chronic sinusitis and the yellow nail syndrome. AB - Diagnosing syndromes that include chronic sinusitis can expedite the management of both conditions. Yellow nail syndrome is usually described as the combination of yellow nails, lymphoedema and often respiratory manifestations such as chronic sinusitis, bronchiectasis and pleural effusions. The pathology responsible for the syndrome is believed to be lymphatic hypoplasia. Diagnosis of yellow nail syndrome is clinical not requiring any specialized tests. In the two cases described, the respiratory tract manifestations required the most active investigation and management. The significance of this syndrome to the otolaryngologist is discussed. PMID- 2246585 TI - Giant enterocystoma within an infant's tongue. AB - A rare developmental cyst within the tongue and submandibular triangle of a male infant containing heterotopic gastric and intestinal epithelium (enterocystoma) is described and its derivation discussed. This cyst was of such a size as to cause feeding difficulties and partial airway obstruction during sleep. Following C.T. scanning, total obstruction necessitated an emergency tracheostomy. Successful enucleation via a median labiomandibulotomy was performed without further complication and two years later there is no sign of recurrence. PMID- 2246586 TI - Temporal arteritis presenting as a submandibular swelling. AB - Temporal arteritis (giant cell arteritis) is a disease of protean manifestation. A case which presented as a submandibular swelling is reported. PMID- 2246587 TI - Direct extension of laryngeal carcinoma to the skin of the neck. AB - Invasion of the skin of the neck by laryngeal carcinoma is relatively uncommon. Twelve cases of cancer of the larynx fungating through the cervical skin are presented. They mostly followed initial treatment by deep X-ray therapy or partial laryngectomy. A high tracheostomy was also considered to be a contributing cause for the occurrence of such a mishap. The management and follow up of these patients is described. PMID- 2246588 TI - Late development of a squamous carcinoma in a reconstructed pharynx. AB - We report a case in which a squamous cell carcinoma was found to have arisen from a delto-pectoral skin flap used in pharyngeal reconstruction. The flap had been forming a neo-pharynx for 24 years. No other signs of recurrent disease had developed in this period. This raises the possibility of tumour induction in heterotopic skin used for oropharyngeal reconstruction. PMID- 2246589 TI - Parapharyngeal abscess and torticollis. AB - The combination of a parapharyngeal abscess and torticollis in an adult, due to a spastic contraction of the sterno-cleido-mastoid muscle is an extremely rare condition. We have recently been exposed to such case, in which it was very difficult to make the diagnosis and where CT of the neck gave us the answers without any difficulty. The indication for CT at an early stage in unexplained neck infections is stressed. PMID- 2246590 TI - Haemangiosarcoma of the maxillary antrum. AB - Angiosarcomas are extremely rare in the head and neck and the histological diagnosis is often difficult. We present a case of a haemangiosarcoma of the maxillary antrum in a 33 year old male. The histological diagnosis and subsequent management are discussed. PMID- 2246591 TI - Multiple submucosal out-fractures of inferior turbinates. PMID- 2246592 TI - Nebulized adrenaline. PMID- 2246593 TI - Response to Kronick. PMID- 2246594 TI - The learning mystique. PMID- 2246596 TI - Special education teachers: technicians or educators? PMID- 2246595 TI - Health fraud. PMID- 2246597 TI - A self-advocacy plan for high school students with learning disabilities: a comparative case study analysis of students', teachers', and parents' perceptions of program effects. AB - This qualitative study examined immediate perceived effects of a self-advocacy plan for students with learning disabilities (LD) in a 4-year comprehensive high school. The study's design was based on information-processing theory and qualitative research techniques, such as participant/observation and interviews. Subjects were 15 ninth- and tenth-grade students with LD, their parents, and their resource teachers. Participants responded to standardized open-ended interview questions upon completing the first step of the Self-Advocacy Plan. The study suggests that the Self-Advocacy Plan is an effective program increasing students' awareness of the vocational and academic services they qualify for, clarifying their perceptions of their roles as learners and individuals with LD, increasing their understanding of LD as a condition that has certain general characteristics, and developing their awareness of career and educational opportunities. The study provides suggestions for future self-advocacy research and for special educators who wish to design programs for students with LD incorporating the concepts of psychosocial development of the individual, information-processing theory, and self-advocacy. PMID- 2246598 TI - The self-perception of a learning disability and its relationship to academic self-concept and self-esteem. AB - Eighty-seven children with learning disabilities, aged 9 through 11 years 11 months, completed measures of self-esteem, academic self-concept, and self perception of their learning disability. The Self-Perception of Learning Disability (SPLD) instrument measures the extent to which children with learning disabilities perceive their disability as (a) delimited rather than global, (b) modifiable rather than permanently limiting, and (c) not stigmatizing. It was hypothesized that self-perception of one's learning disability would be related positively to both academic self-concept and self-esteem, and that each of these relationships would remain significant when controlling for sex, ethnicity, age, reading and math achievement, self-contained versus mainstreamed classroom setting, and age at diagnosis. Correlations and multiple regression analyses confirmed these hypotheses. Results were discussed in terms of helping children to develop less negative self-perceptions of their disabilities. PMID- 2246599 TI - Metaphoric competence in children with learning disabilities. AB - Metaphoric competence was examined in two groups of children with learning disabilities and one group of nondisabled peers ranging in age from 9-0 to 11-0 years. There were five girls and seven boys in each group. One group of students with learning disabilities had a history of spoken language impairment and the other group did not. Subjects were administered three verbal metaphor tasks (comprehension, preference, and completion) and a visual metaphor task, the Metaphor Triads Task (MTT). The three verbal metaphor tasks were administered in three contexts: (a) sentence, (b) story, and (c) story plus visual (pictorial) support. The group with a history of language impairment consistently performed more poorly on the metaphor tasks than the group without a history of language impairment, who, in turn, performed more poorly than the nondisabled children on all but the MTT. Context variations had no effect on children's performance. Theoretical and clinical implications will be discussed. PMID- 2246600 TI - LD status and achievement: confounding variables in the study of children's social status, self-esteem, and behavioral functioning. AB - The purpose of the present study was to examine the role of achievement in explaining the poor social and behavioral functioning associated with LD status, and to evaluate potential gender differences in patterns of interpersonal functioning among youth with learning disabilities (LD) and nondisabled (NLD) youth. Thirty-two students with learning disabilities (21 boys, 11 girls) were matched with same-sex, same-race classmates whose reading achievement was low (LA) or average (AA), and these groups were compared on peer ratings of liking and disliking, perceptions of self-worth and social acceptance, and teacher ratings of conduct problems, anxiety-withdrawal, and attention problems. Students with learning disabilities were less accepted and less well-liked than children in the LA or AA groups and also perceived their self-worth and social acceptance to be lower than LA or AA students. Group by Sex interactions were apparent for several of the peer rating and behavioral variables, indicating that different patterns of social and behavioral functioning distinguished LD boys and LD girls from their NLD peers. The findings highlight the potential role of low achievement in peers' dislike of LD girls and suggest the importance of investigating well-defined subgroups of youth with LD in future research. PMID- 2246601 TI - An analysis of WISC-R factors for gifted students with learning disabilities. AB - Intellectual patterns of gifted students with learning disabilities were studied to determine cognitive factors characterizing these children. Twenty-four gifted children with learning disabilities (LD) and a control group of nondisabled gifted children were administered the Wechsler Intelligence Scale for Children Revised (WISC-R) (Wechsler, 1974). While differences between the two groups on individual subtests were examined, a comparison of broader factors was emphasized in discovering cognitive patterns that might suggest effective intervention. Experimental and control performances were compared on 14 factor scores, using cognitive classification systems of Bannatyne (1971), Kaufman (1975), Rapaport, Gill, and Schafer (1946), and Wechsler (1974). Gifted students with LD were more reliant on verbal conceptualization and reasoning than the control students. They also demonstrated deficiencies in short-term auditory memory and sound discrimination. The gifted group with LD exhibited the Organic Brain Syndrome factor (Wechsler, 1974) to a significantly greater extent than did the control group. PMID- 2246602 TI - Teacher perceptions of differences among elementary students with and without learning disabilities in referred samples. AB - Current referral and identification procedures for students with learning disabilities (LD) have been criticized on conceptual and procedural dimensions, including difficulties in operationalizing the definition and in making eligibility decisions that are data based. Recognizing these difficulties, the Texas Education Agency appointed a task force to examine various issues associated with the identification, assessment, and programming of students with LD. Task force members recognized the need to identify classroom behaviors that differentiate students with LD from their non-disabled peers. Two scales of 83 items each were devised and piloted in 70 school districts. Five significant factors or subscales were identified through discriminant factor analyses. Two subscales and 18 individual items discriminate students later classified as LD and those referred but not subsequently classified as LD. Results are discussed, with implications for further investigation of behaviors that distinguish students with and without LD. PMID- 2246603 TI - Learning disability, inferential skills, and postfailure reflectivity. AB - Children with learning disabilities (LD) were compared with normally achieving children (NA) on two aspects of problem solving: inferential skills and response to errors in an academic content-free task. We tested 33 normally achieving children and 69 children with LD, aged 7 years 10 months to 16 years 4 months, on the PAR (PAttern Recognition) task, a computer-based, self-paced learning sequence. The children with LD were subtyped in two different ways: first, as children with only an arithmetic disability (AD), or with both arithmetic and word-recognition disabilities (AD/WRD); and second, as children with LD and attention deficit disorder (ADD), or LD without ADD. Results showed that on inferential skills, children with LD (without subtyping), children with AD/WRD, and children with LD with and without ADD scored significantly lower on the PAR task than children in the NA group. Also, an interaction was found between the NA and LD (without subtyping) groups and age, whereby children with LD improved their scores on PAR with age significantly more than normally achieving children. On attention to errors, children with both arithmetic and word-recognition disabilities scored significantly lower than children with only arithmetic disability or NA. It appears that the meta-cognitive skill of monitoring errors may be a major source of difficulty in problem solving for children with both arithmetic and word-recognition disabilities. PMID- 2246604 TI - The relative value of reading ability and IQ as predictors of teacher-reported behavior problems. AB - Measures of early family adversity, pre-school-age IQ, school-age IQ, and reading ability were obtained from 779 Dunedin children. The data were used to examine the role of reading ability in the relationship between intellectual performance and teacher-reported behavior problems. Results of regression analyses showed that family adversity and pre-school-age IQ predicted problem behavior during the first year at school. However, reading scores accounted for a larger proportion of the variance in the later behavior problem scores than did school-age IQ scores, and when reading ability was entered in the regression equation before IQ, then reading but not IQ significantly predicted change in problem behavior during the primary school years. The results indicated that the association between IQ scores and problem behavior was mediated by reading ability and that a measure of school-age IQ has limited usefulness for models of primary school-age problem behavior. PMID- 2246605 TI - A descriptive study of adults with suspected learning disabilities. AB - This article documents a descriptive study of 80 adults considered to have learning disabilities. The study was initiated by the Language and Learning Disabled Adults Task Force in London, Ontario, for the purpose of developing a profile of the self-perceived characteristics and needs of the adult population with learning disabilities in Southwestern Ontario. The study also served as a vehicle for implementation of the Intake Questionnaire, an instrument with potential as a screening device for service agencies working with adults with learning disabilities. A self-referred and agency-referred sample of 80 adults completed the Intake Questionnaire. Data were collected in the areas of demography, education, employment, health, and psychosocial characteristics, aspirations, and cooperation with further testing. Results describe people with ongoing specific problems in education, employment, and psychosocial functioning who aspire to learn more about themselves and their learning disabilities. PMID- 2246606 TI - 26-Hydroxycholesterol: synthesis, metabolism, and biologic activities. AB - Cholest-5-ene-3 beta,26-diol (26-hydroxycholesterol) is synthesized by a mitochondrial P-450 enzyme that appears to be widely distributed in tissues. Together with other C-27 steroid intermediates it is transported to the liver and metabolized to bile acids. Although 26-hydroxycholesterol is transported in plasma lipoproteins mostly as the fatty acid ester, neither its assembly and orientation within lipoproteins nor its mechanism of transport across the sinusoidal liver membrane is known. Cell culture studies indicate that 26 hydroxycholesterol can inhibit both cholesterol synthesis and low density lipoprotein (LDL) receptor activity. Inhibition of DNA synthesis also occurs and may not be related to the reduction in HMG-CoA reductase activity. The relationship of these in vitro activities to the physiologic role(s) of 26 hydroxycholesterol remains to be clarified. A clue to its biologic role is the knowledge that markedly decreased 26-hydroxylase activity appears to be the molecular basis of cerebrotendinous xanthomatosis, an inborn error of metabolism characterized by a significant decrease in 26-hydroxycholesterol and bile acid synthesis and an increase in cholesterol synthesis. PMID- 2246607 TI - Retinol metabolism in rats with low vitamin A status: a compartmental model. AB - A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of [3H]retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver (9.0, 8.2, and 5.8 micrograms retinol equivalents/day, respectively), coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma. Similarly, of the vitamin A that entered the carcass, approximately 76% was returned to the plasma. All of the retinol that entered the kidneys was modeled as recycling to the plasma. The present studies provide quantitative and descriptive evidence of an efficient metabolism of vitamin A from absorption through turnover and utilization in rats with very low vitamin A status. Furthermore, although their body stores of vitamin A were extremely low, these rats maintained a high level of recycling of vitamin A throughout the body. PMID- 2246608 TI - Effects of fish oil on VLDL triglyceride kinetics in humans. AB - Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDL-TG synthetic rate from 23 +/- 14.3 (mean +/- SD) to 12.6 +/- 7.5 mg/h per kg ideal weight (P less than 0.005) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 +/- 0.12 to 0.38 +/- 0.16 h -1 (P less than 0.005). At the same time, there was a 66% reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 +/- 317 to 87 +/- 77 mg/dl; P less than 0.005). There was a strong correlation (r = 0.83; P less than 0.01) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolism cannot be ruled out. PMID- 2246609 TI - Concentration of neutral lipids in the phospholipid surface of substrate particles determines lipid transfer protein activity. AB - To better understand the mechanism of lipid transfer protein (LTP) action and the effects of altered lipoprotein composition on its activity, we evaluated the dependence of LTP activity on the concentrations of cholesteryl ester (CE) and/or triglyceride (TG) in the phospholipid bilayer of substrate particles. Phosphatidylcholine (PC)-cholesterol liposomes containing up to 2 mole% TG and/or CE were prepared by cholate dialysis and used as either the donor of lipids to, or the acceptor of lipids from, low density lipoproteins (LDL). CE or TG transfer from liposomes of varying neutral lipid content to LDL showed saturation kinetics with an apparent Km of less than or equal to 0.2 mole%. Throughout this concentration-dependent response. PC transfer, which depended on the same LTP donor particle binding interactions as those required for neutral lipid transfer, was essentially unchanged. Lipid transfer in the reverse direction (from LDL to liposomes of varying neutral lipid content) followed the same kinetics showing that transfer between the two particles is tightly coupled and bidirectional. When liposomes contained both TG and CE, these lipids competed for transfer in a manner analogous to that previously noted with lipoprotein substrates. In conclusion, CE and TG transfer activities are determined by the concentration of these lipids in the phospholipid surface of donor and acceptor particles. At low TG and CE concentrations, LTP bound to the liposome surface as indicated by PC transfer, but only a portion of these interactions actually facilitated a neutral lipid transfer event. Thus, the overall rate of neutral lipid transfer, and the competition between TG and CE for transfer, depend on the concentrations of these lipids in the phospholipid layer. PMID- 2246610 TI - Role of cholesteryl ester transfer protein (CETP) in the HDL conversion process as evidenced by using anti-CETP monoclonal antibodies. AB - The implication of cholesteryl ester transfer protein (CETP) in the high density lipoprotein (HDL) conversion process was studied by incubating HDL3 with a purified CETP preparation for 24 h at 37 degrees C. At a physiological plasma level, CETP induced a decrease of the HDL3 fraction (8.6 nm diameter) and the appearance of two new distinct particle subpopulations with mean diameters of 9.5 and 7.8 nm. To determine whether the effects of the CETP preparation could be assigned to CETP itself, the incubations were conducted either in the absence or in the presence of specific anti-CETP monoclonal antibodies. The HDL3 conversion process induced by the CETP preparation was totally blocked by addition to the incubation mixture of TP1 anti-CETP monoclonal antibody, known to completely inhibit the cholesteryl ester transfer activity in vitro. Moreover, the HDL conversion activity was retained, together with the CETP activity, on an anti CETP affinity column and was insensitive to the presence of a lecithin:cholesterol acyltransferase inhibitor. Compared with incubations with CETP, incubations with CETP and apoA-IV increased the size range redistribution of the HDL3 particles, particularly by promoting the formation of very small sized lipoprotein particles. The results of the study demonstrate thhat CETP can mediate an HDL size conversion even in the absence of lipid transfers between HDL and other lipoprotein fractions. They constitute a supplementary argument for a multipotential role of CETP in lipid transport. PMID- 2246611 TI - Differences in carbohydrate content of low density lipoproteins associated with low density lipoprotein subclass patterns. AB - The neutral carbohydrate content of both the protein (apoB) and lipid fractions of low density lipoproteins (LDL) from subjects with a predominance of small, dense LDL (subclass pattern B) was found to be lower than in subjects with larger LDL (subclass pattern A): 45 +/- 12 versus 64 +/- 13 mg/g apoLDL, and 58 +/- 8 versus 71 +/- 8 mg/g apoLDL (P less than 0.0005 for both). Sialic acid content of LDL lipids, but not apoB, was also reduced in subclass pattern B. ApoB and glycolipid carbohydrate content of total LDL and LDL density subfractions declined with increasing LDL density and decreasing particle diameter. Moreover, in LDL subfractions from pattern B subjects, carbohydrate content of LDL apoB, but not LDL glycolipid, was significantly lower in comparison with particles of similar size from pattern A subjects. Thus, in LDL subclass pattern B, reductions in LDL carbohydrate content are associated both with reduced concentrations of larger carbohydrate-enriched LDL subclasses, and with reduced glycosylation of apoB in all LDL particles. LDL glycolipids may vary with overall lipid content of LDL particles, but variation in apoB glycosylation may indicate differences in pathways for LDL production, and reduced apoB glycosylation may reflect the altered metabolic state responsible for LDL subclass pattern B. PMID- 2246612 TI - Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryothin sections. AB - The distribution of apolipoprotein (apo) E in rat hepatocytes was investigated with an affinity-purified polyclonal antibody raised against apoE isolated from hepatogeneous very low density lipoproteins (VLDL). The distribution of this antibody was visualized with colloidal gold complexed to anti-rabbit IgG. By epipolarization microscopy, apoE was found uniformly along the basolateral surfaces of all hepatic parenchymal cells, showing a striking intensity along the sinusoidal front. Punctate deposits of colloidal gold appeared to be randomly distributed within all hepatocytes. Widely scattered Kupffer cells also stained for apoE. Electron microscopic examination of immunogold-labeled cryothin sections showed that hepatocytic microvilli projecting into the space of Disse consistently contained clusters of immunogold. The gold particles were variably associated with evident lipoprotein particles, raising the possibility that apoE alone may bind to receptors or other macromolecules at the surface of hepatocytes. Endosomes near the sinusoidal front and multivesicular bodies in the Golgi/biliary area labeled intensely for apoE, consistent with a high content of apoE associated with triglyceride-rich lipoprotein remnants contained within these organelles. Some but not all nascent VLDL particles within putative forming Golgi secretory vesicles were labeled, but many other Golgi vesicles and cisternae that lacked evident VLDL particles were also labeled. These results suggest that at least some apoE associates with nascent VLDL in forming Golgi secretory vesicles. Unexpectedly, the matrix of all hepatocytic peroxisomes was heavily labeled. Immunoblots with the affinity-purified anti-rat apoE IgG against proteins from highly purified peroxisomes isolated from rat hepatocytes revealed a protein with an apparent molecular mass of 34.5 kDa, similar to that of rat apoE in rat blood plasma. In addition, gold was sometimes found in the area either adjacent to peroxisomes or between multivesicular bodies and the bile canaliculus not evidently associated with a membranous compartment. These observations suggest that apoE may participate in interorganellar cholesterol transport within hepatocytes. PMID- 2246613 TI - Lysosomal acid lipase deficiency in rats: lipid analyses and lipase activities in liver and spleen. AB - We report the biological characterization of an animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected rats accumulated cholesteryl esters (13.3-fold), free cholesterol (2.8-fold), and triglycerides (5.4-fold) in the liver, as well as cholesteryl esters (2.5-fold) and free cholesterol (1.33-fold) in the spleen. Triglycerides did not accumulate, and the levels actually decreased in the spleen. Analysis of the fatty acid composition of the cholesteryl esters and triglycerides showed high percentages of linoleic acid (18:2) and arachidonic acid (20:4) in both organs, especially in the liver. No accumulation of phospholipids, neutral glycosphingolipids, or gangliosides was found in the affected rats. Acid lipase activity for [14C]triolein, [14C]cholesteryl oleate, and 4-methyl-umbelliferyl oleate was deficient in both the liver and spleen of affected rats. Lipase activity at neutral pH was normal in both liver and spleen. Heterozygous rats showed intermediate utilization of these substrates in both organs at levels between those for affected rats and those for normal controls, although they did not accumulate any lipids. These data suggest that these rats represent an animal counterpart of Wolman's disease in humans. PMID- 2246614 TI - Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment. AB - Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil. Regulation of cholesterol metabolism by dietary squalene in man is unknown, even though olive oil users in Mediterranean areas have low serum cholesterol levels. We have investigated absorption and serum levels of squalene and cholesterol and cholesterol synthesis with the sterol balance technique and serum levels of cholesterol precursors in humans during squalene feeding (900 mg/d for 7-30 days). The results were compared with those during cholestyramine treatment. Fecal analysis suggested that about 60% of dietary squalene was absorbed. Serum squalene levels were increased 17 times, but serum triglyceride and cholesterol contents were unchanged. The squalene feeding significantly (P less than 0.05) increased serum levels of free (1.7-2.3 times) and esterified (1.9-2.4 times) methyl sterol contents, while elevations of free and esterified delta 8-cholesterol and lathosterol levels were inconsistent. Cholestyramine treatment modestly augmented free methyl sterol levels (1.3-1.7 times), less consistently than those of esterified ones, while, in contrast to the squalene feeding, serum contents of free and esterified delta 8-cholesterol and lathosterol were dramatically increased (3.3-8 times). Neither of the treatments significantly affected serum plant sterol and cholestanol levels. The squalene feeding had no consistent effect on absorption efficiency of cholesterol, but significantly increased (paired t-test, P less than 0.05) the fecal excretions of cholesterol and its nonpolar derivatives coprostanol, epicoprostanol, and coprostanone (655 +/- 83 SE to 856 +/- 146 mg/d) and bile acids (212 +/- 24 to 255 +/- 24 mg/d), indicating an increase of cholesterol synthesis by about 50%. We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels. The clearly increased serum contents of esterified methyl sterols may reflect stimulated tissue acyl CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity during squalene feeding as these sterols are not esterified in serum. PMID- 2246615 TI - Composition and synthesis of glycolipids in megakaryocytes and platelets: differences in synthesis in megakaryocytes at different stages of maturation. AB - The composition and synthesis of megakaryocyte and platelet glycolipids were compared since these lipids are thought to be important for biologic activities such as adhesion and maturation. Highly purified guinea pig megakaryocytes at different stages of maturation and platelets were studied. Glycolipids and gangliosides were extracted, separated by thin-layer chromatography, and the carbohydrate content was analyzed by gas-liquid chromatography (GLC). Synthesis of ceramides and glycolipids was determined by the incubation of megakaryocytes with [14C]acetate, [3H]palmitic acid, and [3H]galactose. A major neutral glycolipid present in guinea pig megakaryocytes and platelets was identified as asialoGM2 by selective enzymatic hydrolysis with beta-N-acetylhexosaminidase, alpha-galactosidase and endo-beta-galactosidase, and carbohydrate analysis by GLC. Trace amounts of asialoGM1 were detected immunologically. The cells also contained glucosyl ceramide and lactosyl ceramide. Several ganglosides were detected of which one was identified as GM1 by its reaction with the beta-subunit of cholera toxin and by the identification of an asialoGM1 core with anti asialoGM1 antibody after desialylation. The synthesis of ceramides from palmitic acid and acetate was 5 and 10 times greater, respectively, in megakaryocytes than in platelets. Ceramide and glycolipid synthesis from palmitic acid occurred primarily in immature megakaryocytes while synthesis from acetate occurred primarily in more mature megakaryocytes. The glycosylation of ceramides from galactose was 42 times greater in megakaryocytes than in platelets. Thus, ceramides and glycolipids are primarily synthesized in megakaryocytes, but platelets retain the capacity to synthesize significant amounts of free ceramides. The glycosylation of free ceramides occurs almost exclusively in megakaryocytes and only in trace amounts in platelets. These data indicate that megakaryocytes determine the composition of glycolipids in platelets and that there is considerable compartmentalization of glycolipid synthesis and membrane assembly at various stages of megakaryocytes development. PMID- 2246616 TI - Serine-palmitoyl transferase activity in cultured human keratinocytes. AB - Sphingolipids comprise approximately 25% of the stratum corneum lipids and are considered critical constituents of the epidermal permeability barrier. Whether sphingoid base structures are synthesized in the epidermis or whether they are derived from circulating or dermal sources is not known. We report here the initial characterization of serine-palmitoyl transferase (EC 2.3.1.50; SPT), the rate-limiting enzyme in the synthesis of sphingolipids, from cultured human neonatal keratinocytes. Subcellular fractionation studies demonstrated that 79% of the total cellular SPT activity was associated with the microsomes. The specific activity of keratinocyte SPT was 270 +/- 20 pmol/min per mg of microsomal protein, a level significantly higher than activities reported in other tissues. Keratinocyte SPT showed an apparent Km for L-serine of 0.40 (+/- 0.04 mM, with an alkaline pH optimum (8.2 +/- 0.4). Keratinocyte SPT utilizes palmitoyl-CoA preferentially over other saturated or unsaturated acyl-CoA substrates; increasing acyl-CoA chain lengths above C16 by one or two carbons was less detrimental to activity than similar decrements in chain length. Finally, the mechanism-based inhibitors L-cycloserine and beta-chloro-L-alanine, demonstrated potent inhibition of keratinocyte SPT activity, with 50% inhibitory concentrations of approximately 3.0 and 25 microM, respectively. In summary, we have found that cultured human neonatal keratinocytes contain unusually high levels of serine-palmitoyl transferase activity, and that the substrate specificity of keratinocyte SPT may determine the base composition of epidermal sphingolipids. PMID- 2246617 TI - Ultrastructural localization of plasma retinol-binding protein in rat liver. AB - Immunocytochemical studies were carried out to examine the subcellular localization of plasma retinol-binding protein (RBP) in rat liver. The studies used normal, retinol-deficient, and retinol-repleted retinol-deficient rats with or without colchicine pretreatment. Affinity-purified monomeric Fab' fragments from the IgG fraction of rabbit anti-rat RBP were conjugated to horseradish peroxidase. This conjugate effectively penetrated into tissue sections and enabled RBP to be localized by high resolution immunoelectron microscopy. In the normal liver parenchymal cell, RBP was found to be localized in the synthetic and secretory structures including endoplasmic reticulum (ER), Golgi complex (GC), and secretory vesicles. With the method used, significant localization of RBP was not observed in hepatic cells other than parenchymal cells. The distribution of RBP-positive areas within parenchymal cells changed markedly with retinol depletion. Thus, a heavy accumulation of RBP in the ER, accompanied by a marked decrease of the RBP-positive GC and secretory vesicles, was demonstrated in liver parenchymal cells from retinol-deficient rats. After repletion of deficient rats with retinol, the RBP that accumulated in the ER appeared to move rapidly from the ER through GC and secretory vesicles to the cell surface. Pretreatment with colchicine led to marked increase in RBP-positive secretory vesicles in retinol repleted rat liver parenchymal cells. The results reported here demonstrate that the specific block in hepatic RBP secretion seen in retinol deficiency involves an inhibition of the movement of RBP from the ER to the GC in the parenchymal cell. PMID- 2246618 TI - ELISA measurement of LDL receptors. AB - An enzyme-linked immunosorbent assay was developed for measurement of low density lipoprotein (LDL) receptors. A monospecific polyclonal antibody to LDL receptor purified from rat liver that reacted with rat, mouse, canine, and human LDL receptor was used. With this assay, LDL receptors could be measured on 2-4 x 10(5) adherent cells and 1.0 x 10(5) cells in suspension, although results were more variable with cell suspensions. Membranes from a variety of receptor-rich and receptor-poor tissues could be assayed directly after adherence of the membranes to the ELISA plate by an overnight incubation. In some instances, the quality of the assay was improved by first solubilizing the membranes. The sensitivity of the assay is such that between 0.15 and 2 micrograms of membrane protein is required. This could be obtained from leukocytes in a modest (20-30 ml) quantity of human blood. The assay was used to demonstrate the rapid down regulation of LDL receptors in human mononuclear leukocytes in response to a cholesterol-containing meal. Overall, the results support the use of ELISA technology to measure LDL receptors, particularly for physiologic studies. PMID- 2246619 TI - Electronic determination of size and number in isolated unfixed adipocyte populations. AB - Adipose tissue cellularity and metabolism are traditionally expressed in terms of mean cell size and number. The need for a simple method allowing rapid determination of cell size and number of freshly isolated, unfixed adipocyte preparations led us to compare estimates of cell size determined by the established method of optical sizing to a proposed method of electronic cell sizing and counting. In collagenase-isolated, unfixed adipocytes whose mean diameters ranged from approximately 40 to 65 microns (obtained from healthy rats weighing 100-360 g) the electronic method provided estimates of the mean cell diameter and size distribution that did not differ from the optical sizing technique. Estimates of mean cell diameter and cell number by the electronic method were rapid and reproducible (coefficients of variation 0.5 and 3.8%, respectively) and a less than 20 sec delay until sample analysis, after mixing of the adipocyte suspension, did not alter these estimates. Electronic determination of cell size and number, using freshly isolated, unfixed rat adipocyte populations (mean cell diameter less than or equal to 60 microns), is rapid and reliable. It will be particularly useful for studies of hormone binding and transport processes where it may be necessary to tightly control cell density. PMID- 2246620 TI - HPLC resolution of diacylglycerol moieties of natural triacylglycerols on a chiral phase consisting of bonded (R)-(+)-1-(1-naphthyl)ethylamine. AB - Chiral phase high performance liquid chromatographic resolution of sn-1,2(2,3)- and X-1,3-diacylglycerols generated by partial Grignard degradation from natural triacylglycerols was carried out using a chiral column (25 cm x 4.6 mm i.d.) containing (R)-(+)-1-(1-napthyl)ethylamine polymer chemically bonded to 300A wide pore spherical silica (5 microns particles). The diacylglycerols were chromatographed as 3,5-dinitrophenyl-urethanes and detected at 226 or 254 nm UV. By an isocratic elution with n-hexane- 1,2-dichloroethane-ethanol 40:10:1 (v/v/v) as the mobile phase, the sn-1,2(2,3)-diacylglycerols from corn, linseed, and menhaden oils were resolved into two clearly distinguishable enantiomer groups, although some peak overlappings between the enantiomers were observed in the linseed and menhaden oil diacylglycerols. In addition to the excellent enantiomer resolution, each enantiomer and the X-1,3-isomers were partially resolved into several peaks, which could be tentatively identified on the basis of equivalent carbon number. It is concluded that chiral phase high performance liquid chromatography can be utilized for effective resolution, identification, and quantitation of enantiomeric diacylglycerols from complex natural mixtures. PMID- 2246621 TI - Enzymatic synthesis of phosphatidylserine on small scale by use of a one-phase system. AB - A modification of the phospholipase D-catalyzed synthesis of phosphatidylserine is described, which allows the handling of small quantities of lipid without the need for an ether-water system. By using octylglucoside to disperse the lipid during the enzymatic conversion, it was possible to reduce the volume of the reaction mixture to 50-100 microliters. The amount of lipid that can be handled in such small volumes is in the order of micrograms. This facilitates the synthesis of phosphatidylserine from rare or expensive phosphatidylcholine species. The yield of phosphatidylserine is increased by replacing phospholipase D from cabbage by the enzyme from Streptomyces species. PMID- 2246622 TI - A modified qualitative test for bilirubin in the urine. AB - A new technique for determination of urinary bilirubin has been described. Evaluation of the new test by simultaneous testing with Harrison's test on 76 urine samples has assured the validity of the new technique. The advantages of the new test include low cost, its simple procedure, and the great convenience of transportation to any working sites. PMID- 2246623 TI - Serum thiocyanate concentrations in smoking and non-smoking males. AB - The determination of serum thiocyanate is a simple and inexpensive method in assessing smoking status. It can be used alone or as adjuvant to other methods. We have found the thiocyanate method to be efficient for this particular purpose. PMID- 2246624 TI - The surgical treatment of intracranial meningiomas at Songklanagarind Hospital. AB - The characteristics of our meningiomas are the same as in the literature. It is the fruit of hard labor of a new center in the South of Thailand. The recurrence and mortality rate is very low, but the follow-up periods are too short to assess this aspect cogently. PMID- 2246625 TI - Effect of recombinant DNA human growth hormone in Thai children with growth hormone deficiency. AB - We conclude that recombinant DNA methionine-free hGH treatment of GH-deficient Thai children is very effective in the first year of treatment. No patients reported any side effects or resistance to treatment. PMID- 2246626 TI - Ovarian neoplasms in childhood and adolescents in Songklanagarind Hospital, February 1983-March 1989. AB - Ovarian tumors in young females under the age of 20 years in Songklanagarind Hospital from February 1983 to March 1989 were evaluated. The total number of patients was 47, with a 4.0 per cent incidence of ovarian tumors in all age groups. Germ cell tumor was the most common tumor (59.6%) and 60.7 per cent were malignant. The chief presenting symptom was abdominal distention or mass, with 17.0 per cent of torsion. Ascites and solid consistency of tumors suggested its malignant potential. Surgery was the treatment for all patients with a conservative approach in the majority of cases and supplemented with chemotherapy and/or radiotherapy in malignant cases. PMID- 2246627 TI - Weight-control training-models for obese pupils in Bangkok. AB - The increased prevalence of obese children in schools in Bangkok from 12.7 to 14.3 per cent between 1986-1987, and the health risk of obesity of cardiovascular diseases, requires effective training models for behavior modification. The effects of 4 training models: problem-solving, lecturing, lecturing + reward and self-learning developed by the researchers, on the changes of knowledge and weight/height of 90 obese pupils, were compared with those of other 20 obese pupils in the control group. The comparison of height, weight and weight/height, including knowledge of the obese pupils, before training, between training and control groups, showed no significant difference. At the end of the 3-month training period, pupils' knowledge of obesity had increased significantly by all training models, without any difference among groups. The change of weight during the training period showed no significant difference, both within and among groups, except within the lecturing + reward group which had decreased significantly. At the end of 6 months' follow-up, the increase of weight/height (after-before), differed significantly, both within and among groups, with the highest increase in the control group, followed by self-learning, lecturing, problem-solving, and lecturing + reward. The weight-increase that had not differed significantly, was found in the problem-solving group only. If the percentages of the obese pupils whose weight/height were reduced, were considered, the highest reduction was in the problem-solving (31.8%), lecturing (28.6%), lecturing + reward (22.7%), and self-learning (20%). There was no obese pupil in the control group whose weight/height was reduced, throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246628 TI - Hemolytic uremic syndrome associated with Shigellosis: a report of 8 cases. AB - During an outbreak of dysentery in the Northeastern part of Thailand, eight cases of HUS were admitted to Srinagarind Hospital from April to September 1987. Their ages ranged from 6 months to 6 years (mean age = 2.4 years). All patients had prodromal symptoms of mucous bloody diarrhea. The stool culture was positive for Shigella dysentery type I in one case. The treatment included blood transfusion, peritoneal dialysis, exchange transfusion and supportive treatment. One patient died from nosocomial septicemia. For the survivors, platelets count returned to normal after 7 to 19 days (mean 12.8 days). The duration of azotemia ranged from 12 to 36 days (mean = 20 days). One patient was azotemic during 40 days of hospitalization. PMID- 2246629 TI - The regression of recurrent conjunctival papillomas by lymphoblastoid interferon treatment. PMID- 2246630 TI - Intestinal capillariasis: indigenous cases from Chiang Mai and Phayao provinces, Thailand. AB - Two cases of intestinal capillariasis were presented from new locations in northern Thailand, i.e., Phayao and Chiang Mai provinces. Both of them had chronic voluminous diarrhea and malabsorption. It was believed that they acquired the infection indigenously. Both adult worms and their eggs, presented in the feces, were identified as Capillaria philippinensis but with morphological variation. The infection was treated effectively with a prolonged administration of mebendazole. PMID- 2246631 TI - Concussion sequelae. PMID- 2246632 TI - The Journal of Family Practice: a time of transition. PMID- 2246633 TI - A comparison of rapid enzyme immunoassay tests for the detection of Chlamydia trachomatis cervical infections. AB - Two rapid enzyme immunoassay test kits were compared with culture for the detection of Chlamydia trachomatis endocervical infections. Endocervical samples for C trachomatis culture and the two enzyme immunoassay tests were evaluated from 502 county health department and Planned Parenthood patients. The prevalence of infection in this population was 12%. Sensitivity and specificity of the Abbott TestPack Chlamydia were 51.7% and 99.5%, respectively, and of the Kodak Surecell Chlamydia were 76.7% and 98.6%, respectively. The positive and negative predictive values for TestPack were 93.9% and 93.8%, and for Surecell were 88.5% and 96.9%, respectively. Additionally, an in vitro investigation was used to evaluate whether typical office staff (physicians, nurses, medical technicians, receptionists, and radiology technicians) were able to perform competently the tests in each kit. Office personnel tested 12 dilutions of a C trachomatis stock sample or negative control sample as unknowns for each kit in the in vitro investigation. There were no differences among office staff in performance when compared for each test kit. Selective use of these enzyme immunoassay tests for high-risk patients in a family practice population that has a high prevalence of patients with C trachomatis infection may be helpful when rapid test results are required and cultures are not feasible. After appropriate training, most physician office personnel were equally able to perform the enzyme immunoassay tests evaluated. PMID- 2246634 TI - Interpreting office radiographs. A guide to systematic evaluation. AB - Office radiographs are important diagnostic tools for most family physicians, and most family physicians believe that they should be capable of interpreting 90% of these films without referral to a radiologist. Optimal use of these radiographs requires that patients are appropriately selected, that the examination is adequately conducted, and that the films are accurately interpreted. Interpretive accuracy is enhanced if radiographs are analyzed by physicians skilled in observing and interpreting them and if the images are examined in a logical, systematic manner to minimize observer bias. A systematic search pattern is proposed to facilitate family physicians' interpretations for the most common office radiographs: chest, extremities, abdomen, skull, and spine. PMID- 2246635 TI - Management of hypercholesterolemia in a family practice setting. AB - A study was undertaken to assess physician adherence and patient compliance with the National Cholesterol Education Program guidelines for the management of newly detected hypercholesterolemia. The study site was the Department of Family Medicine, Medical University of South Carolina, Charleston, a university-based family medicine residency program. All serum cholesterol levels measured between July 1, 1988, and September 30, 1988, were reviewed. Patients were classified as normal, borderline, or hypercholesterolemic based on serum cholesterol levels and coronary heart disease risk factors. Patients previously recognized to be hypercholesterolemic were excluded. Six months later, medical record reviews were performed for the 192 hypercholesterolemic and 107 borderline hypercholesterolemic patients. Only 39 of the hypercholesterolemic patients (20%) had received appropriate dietary therapy and follow-up. Patient compliance with physician recommendations was excellent. There was minimal unnecessary testing or treatment of borderline hypercholesterolemia. Low rates of appropriate management of hypercholesterolemia may be related to inadequate physician knowledge, low physician-perceived self-efficacy regarding dietary counseling, or time constraints. PMID- 2246636 TI - Outcome of pregnancies experienced during residency. AB - To investigate potential adverse effects of residency training on pregnancy outcome, a cohort study was conducted among 45 university-affiliated residency programs. Outcomes of the first pregnancy experienced during residency were compared between 92 female residents and 144 spouses of male residents. Despite long hours, sleep deprivation, and an increase in perceived stress, the female residents were as likely to give birth to a live, full-term newborn as the spouses of male residents. For white cohort members, an increased risk of premature labor without delivery was identified (RR = 12.3, 95% confidence interval 2.4-61.6). No significant differences were found in prematurity, spontaneous and therapeutic abortions, or presence of congenital abnormalities in the infants. Method of delivery and use of anesthetics and of other medications were similar in both groups. Pregnancy outcomes between the two groups were similar; however, the increased risk for premature labor among female residents is a cause for concern and should be further investigated. PMID- 2246637 TI - The impact of physicians' brief smoking cessation counseling: a MIRNET study. AB - Although many family physicians may discuss smoking cessation with their patients, few do so consistently. A common belief among many physicians is that such efforts will not deter their patients from smoking. Others believe the time commitment required for a successful intervention is excessive. The present study addressed the above issues by examining the effect of a 3- to 5-minute unstructured physician discussion encouraging smoking cessation with family practice patients. Cigarette-smoking patients of two busy family practices in southeast Michigan were randomly assigned to either a control group receiving routine care or an intervention group receiving, in addition to routine care, smoking cessation counseling from their physician. A third comparison group was drawn from smokers in practices not involved in delivering the intervention. Two hundred thirty-eight patients from the intervention group, 178 from the control group, and 47 from the comparison group were followed up with a telephone interview at 6 months. Intervention group patients made significantly more quit attempts than did those in the control group (P less than .001), which was similar to the comparison group. At the 6-month follow-up, 8% of intervention group members, and 4% of both the comparison and control groups reportedly were abstinent from smoking. Among those contacted at the 1-year follow-up, the respective percentages abstinent were 8%, 3%, and 4%. Although these differences in quit rates were not statistically significant, the findings suggest that physicians can positively affect patient smoking cessation. This intervention was feasible in busy family practices, highlighting its generalizability and applicability to other family practice settings in the United States. PMID- 2246638 TI - The do-not-resuscitate order: outpatient experience and decision-making preferences. AB - Do-not-resuscitate (DNR) orders have become a widespread part of modern medical practice. This study examined patient experience and decision-making preferences regarding cardiopulmonary resuscitation. A random sample of 800 outpatients (one half aged over 70 years) was surveyed by questionnaire, with a 51% response rate. While only 11% of patients had ever discussed resuscitation with a physician, 67% had thought about the issue, and 44% had discussed it with someone other than a physician. Patients overwhelmingly preferred to preserve a good quality of life, even if it meant not living longer (93.9%). When asked who they would have help them with DNR decisions, physicians were most often selected, while spouses were the most valued advisors. In a series of scenarios such factors as dementia, drug or alcohol use, age, and pain had a significant effect on a patient's decision about resuscitation. Discussions about DNR issues in the outpatient setting should be encouraged, as patient interest is strong, and greater physician awareness of patients' values and preferences can prevent unwanted resuscitation in the acute setting. PMID- 2246639 TI - Financing graduate medical education in primary care: options for change. AB - The current mechanisms of graduate medical education (GME) financing favor inpatient and procedural care, making the support of primary care programs difficult, as these residencies are oriented toward outpatient evaluation and management. Criteria for evaluating proposals that aim to improve the financial support of primary care programs include the financial, administrative, and educational implications of the options as well as the views of interested stakeholders. Other sources of funding for primary care GME are changes in existing Medicare payments; increased categorical GME funding, ambulatory payment, and grants; commitments from future employers; and redistribution of current funds. Alternatives for spending these funds to aid primary care programs include dividing the sources in three ways: on a per-resident basis, by competitive grants, or by incentives for primary care education. An analysis of the alternatives for changing GME financing shows that several solutions will be needed simultaneously. PMID- 2246640 TI - Routine discussion of advance health care directives: are we ready? An affirmative view. PMID- 2246641 TI - Assessing primary care physicians' knowledge about HIV transmission. PMID- 2246642 TI - A suspected case of carbamazepine-induced hyponatremia. PMID- 2246643 TI - Erythromycin tolerance. PMID- 2246644 TI - Clinical pharmacy in family practice. PMID- 2246645 TI - Pseudocyesis. PMID- 2246646 TI - Immunopathology and viral reactivation. A general theory of schizophrenia. AB - A theory is proposed that explains a broad range of clinical manifestations in schizophrenia. It is a heuristic device for organizing research in the neuroimmunology and virology of schizophrenia. This approach is different from other immune and viral theories of schizophrenia and defines testable hypotheses for further theory refinement or rejection. Defective alpha-interferon (aIFN) regulation resulting in excessive effect is postulated to cause schizophrenia. The role of aIFN in the regulation of development and its induction within the brain by the reactivation of viruses that are commonly present in the normal central nervous system (CNS) are the primary pathophysiological mechanisms. Biological properties of aIFN include neural excitation, opiate and adrenocorticotropic hormone activity, and inhibition of cellular proliferation and differentiation. Psychosis results from in situ viral stimulation of aIFN production in the CNS of a vulnerable host having defective regulation of either sensitivity or production. Negative symptoms result from aIFN effects on CNS development and the behavioral toxicity of aIFN. Biological developmental abnormalities, gender differences in severity, and decline in psychotic symptoms with age are discussed in the context of the theory. Research strategies and specific testable hypotheses are presented. PMID- 2246647 TI - Psychopathology and denial in alleged sex offenders. AB - To investigate whether patients accused of having committed acts of sex offense manifest symptoms of psychopathology and whether they minimize or deny such symptoms during clinical evaluations, we administered the MMPI to 53 alleged sex offenders. We compared patients along two dimensions: a) whether they admitted or denied deviant sexual behavior, and b) whether they faced legal charges for sex offenses. Results indicated the following: a) Patients who denied deviant sexual behavior were significantly more likely to minimize psychopathology than were those who admitted to deviant sexual behavior (p less than .05). b) Patients facing no active legal charges showed significantly more psychopathology than did those facing legal charges (p less than .05). c) The most frequent forms of psychopathology shown by these patients were antisocial attitudes, depression, somatization, and cognitive disorganization. These findings suggest that many alleged sex offenders may experience, and deny, severe psychopathology in addition to their sexual disorders. Clinicians should be alert to subtle signs of psychopathology when evaluating alleged sex offenders who deny deviant sexual behavior, because these patients may be especially likely to minimize symptoms. PMID- 2246648 TI - Working with an interpreter in psychiatric assessment and treatment. AB - Cross-cultural assessment and care frequently involve cross-language communication via a translator, interpreter, or bilingual worker. A resurgence of immigration, legalization of former illegal migrants, and refugee flight to the United States has increased the need for such special means of communication. Psychiatrists and other mental health professionals should develop conceptual models, skills, and experience for conducting cross-language interviews. This article provides information, terminology, and models for one aspect of this special clinical task, i.e., working with translators. PMID- 2246649 TI - An observationally based rating scale for affective symptomatology in child psychiatry. AB - There is growing dissatisfaction with current methods for rating affective symptoms in children. We report findings from a preliminary psychometric study of an alternative approach, that of direct observational ratings. The Emotional Disorders Rating Scale (EDRS) is an observation-based instrument containing 59 items divided into eight subscales. The results of this study indicate that measurement of nonverbal components of affective symptoms in children is feasible. Interrater reliability and internal consistency of the EDRS subscales were high. The EDRS also has potential as a measurement of state-related changes in affective behavior and as a technique for examining treatment response. PMID- 2246650 TI - Multiple muscle enzyme release with psychiatric illness. AB - Associations (p less than .001) between serum concentrations of lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) were observed in physically well patients with mania (N = 100, r = .70), depression (N = 138, r = .51), chronic schizophrenia (N = 85, r = .68), and schizoaffective or atypical psychosis (N = 39, r = .52) discharged from 1978 through 1981. In contrast, there was a negligible association between these enzymes in 90 nonpsychiatric inpatient control subjects. Patients with mania (229.0 +/- 106.1 IU/l) showed significantly (t = 3.16, p less than .002, two-tailed) higher lactate dehydrogenase (LDH) levels than control subjects (191 +/- 41.7 IU/l) and a 14% incidence of abnormally high serum LDH levels vs. 1% among control subjects. Results were unchanged when patients taking neuroleptics were excluded. These results indicate that psychiatric illness, especially mania, induces release of LDH and SGOT, occasionally to unusually high levels. This is similar to previous reports of muscle creatine phosphokinase release in psychiatric patients. Presumably, these enzymes are released from skeletal muscle in association with agitation, with muscle tension, or with blood stasis and local tissue hypoxia consequent to hypoactivity. PMID- 2246651 TI - Long-term outcome of obsessive-compulsive disorder with psychotic features. PMID- 2246653 TI - Prosodic comprehension and expression in schizophrenia. AB - Schizophrenics, manics, depressives and normal subjects (15 in each group) were tested for their ability to understand and express the prosodic quality of speech. Sentences in which one word was stressed (stress prosody comprehension) or in which a particular emotion was conveyed (emotional prosody comprehension) were taped and played to subjects to test their comprehension. Subjects were then asked to read out a list of sentences either stressing a nominated word (stress prosody expression) or conveying a nominated emotion (emotional prosody expression), and their efforts were rated by a panel of normal raters. The main results were 1) that schizophrenics were significantly inferior to the normal group, but equivalent to manics and depressives on emotional prosody comprehension; 2) schizophrenics were significantly inferior to all other groups on emotional prosody expression; and 3) all four groups were equivalently proficient on stress prosody comprehension and expression. The results are interpreted as lending support for the idea that there is an underlying right hemisphere dysfunction in schizophrenia. PMID- 2246652 TI - The brain in schizophrenia. PMID- 2246654 TI - Infarction in the territory of the medial branch of the posterior inferior cerebellar artery. AB - We report 10 cases of cerebellar infarction in the territory of the medial branch of the posterior inferior cerebellar artery (mPICA). Axial sections on MRI through the middle of the medulla and the cerebellum showed the infarction as a triangular area with a dorsal base and a ventral apex directed towards the fourth ventricle. The infarct also involved the lateral and dorsal medulla when the mPICA supplied all or part of these regions. Three clinical patterns were observed: 1) pseudolabyrinthine signs with or without dysmetria and ataxia when the medulla was spared; marked axial lateropulsion was present in most cases; 2) complete or incomplete Wallenberg's syndrome, when the medulla was involved; 3) silent infarction. These syndromes are precisely those previously attributed to PICA occlusion without distinction of the branch involved. No alteration of consciousness was recorded and spontaneous recovery was the rule. Cerebellar infarction in the distribution of the mPICA can be regarded as a benign condition with a good prognosis. PMID- 2246656 TI - Parkinsonian tremor loses its alternating aspect during non-REM sleep and is inhibited by REM sleep. AB - Non-REM sleep transforms the waking alternating Parkinsonian tremor into subclinical repetitive muscle contractions whose amplitude and duration decrease as non-REM sleep progresses from stages I to IV. During REM sleep Parkinsonian tremor disappears while the isolated muscle events increase significantly. PMID- 2246655 TI - Microneurography in relation to intraneural topography: somatotopic organisation of median nerve fascicles in humans. AB - Microneurography was performed in median nerve sensory fascicles with concentric needle electrodes and with conventional tungsten microneedles. The latter electrodes preferentially recorded activity from the myelinated fibres in the whole fascicle. By contrast, due to its special design, a concentric needle can record activity selectively from even a small part of a fascicle. High amplitude signals in C fibres can be discriminated close to Schwann cells that envelope unmyelinated axons. Apart from being biased for activity in thin fibres, the concentric needles can also record signals from nearby myelinated fibres. The palmar receptive fields of such fibre groups were not congruent with the areas traditionally attributed to multiunit skin afferents in humans, namely the innervation zone(s) of one or two adjacent digital nerve(s). Instead, the multiunit fields often comprised small parts of a digital nerve innervation area, frequently only the pulp of a finger. Single units were always localised within previously screened multiunit areas. Contrary to some previously accepted tenets it is probable that single unit activity in myelinated fibres in these studies is recorded extra-axonally near to a node of Ranvier. The findings also suggest the presence of a somatotopy in human limb nerve fascicles, comparable to that previously established in the spinal cord and the somatosensory cortex. PMID- 2246657 TI - The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries. AB - The effects of cyproheptadine, a serotonergic antagonist, were studied in seven patients with spastic paresis of spinal origin. Six patients were included in a double blind crossover trial (maximal dose 24 mg/day). The patients were evaluated on both their spasticity and locomotor function. Four of the patients also participated in an open trial in which cyproheptadine was administered for a minimum of six months at optimal dose. Patients walked on a treadmill at full weight bearing when possible, or with 40% of their body weight externally supported, as required, by an overhead harness system. Cyproheptadine considerably decreased the sustained ankle clonus and episodes of spontaneous spasms observed in all the patients who previously presented these manifestations of spasticity. Two patients who required body weight support (BWS) during locomotion could walk at full weight bearing during cyproheptadine therapy. A more normal timing of EMG patterns in these patients during cyproheptadine therapy was associated with temporal distance changes and marked improvement of joint angular displacement. In contrast, the other patients showed marginal changes in the EMG and the kinematic pattern but eventually managed to walk at a higher speed. These preliminary results suggest that cyproheptadine can reduce spasticity and enhance locomotor function in spinal cord injured patients. PMID- 2246659 TI - Eosinophilic meningitis: cause of a chronic pain syndrome. AB - Three tourists developed eosinophilic meningitis after visiting the Fijian Islands. Two had a severe and long lasting illness with chronic intractable pain. In one patient electrophysiological studies and MRI scan of the brain were abnormal and provided evidence of both radicular and cerebral parenchymal involvement by the most likely causative agent, Angiostrongylus cantonensis. PMID- 2246658 TI - Motor unit discharge characteristics and short term synchrony in paraplegic humans. AB - Frequency of firing and regularity of discharge of human motor units, and short term synchrony between pairs of motor units, have been assessed in extensor digitorum communis (EDC) and tibialis anterior (TA) muscles in control subjects and in clinically complete paraplegic subjects. The discharge pattern of TA motor units in paraplegia ranged from extremely regular to very irregular for different motor units whereas in the control population, and in EDC of both groups, there was a narrow, but intermediate, range of regularity. There was little difference in the incidence and degree of short term synchrony (STS) in EDC between paraplegic and normal subjects. In contrast, virtually no STS of motor units was observed in the TA muscles of the paraplegic group whereas control subjects exhibited approximately the same amount of STS in their TA and EDC muscles. It is concluded that the extra burden placed on arm muscles in paraplegia does not change the amount of synchronisation between motor units. Furthermore, section of the spinal cord does not increase STS as predicted from lesions of the reticulospinal tract in cats. This may reflect the coincidental removal of supraspinal synchronising inputs of motoneurons or the reorganisation of synaptic inputs in chronic paraplegia. PMID- 2246660 TI - Rigid spine syndrome with respiratory failure. AB - The pathogenesis and therapy of respiratory failure in the rigid spine syndrome are discussed in two cases who improved with respiratory assistance. In both cases, the partial pressures of oxygen and carbon dioxide were reversed in arterial blood gas analysis and %VC was less than 30%. Remission from respiratory failure has been obtained by the use of a ventilator during the night. The cause of the respiratory failure in both cases was severe restrictive respiratory dysfunction due to extreme flattening of the chest and fixation of the thorax during respiration as a result of contracture of costovertebral joints. All the previously reported cases of the rigid spine syndrome with respiratory failure died. Appropriate use of the ventilator can improve the prognosis. PMID- 2246661 TI - Learning a unimanual motor skill by partial commissurotomy patients. AB - A series of motor tests on four Chinese partial commissurotomy patients is reported. The single-stage commissurotomy in all four patients included the anterior commissures and two-thirds or four-fifths section of the corpus callosum with sparing of the splenium. There was no demonstrable ability to transfer hand posture in these patients. This was the major evidence for functional deconnexion. A newly learned task of one-hand knotting revealed right hand impairment in all four patients. There was no dyspraxia in the right hand for over-learned object-handling tasks in these patients. It is suggested that there might be right hemisphere specialisation for the initial acquisition of unimanual object-handling skills and that the spared callosal fibres in the splenium alone are insufficient to mediate task control under these conditions. This is supported by the finding that one of these patients, who was the only one who had a right parietal lesion, was unable to perform the newly learned task with either hand. PMID- 2246663 TI - Ferritin in the cerebrospinal fluid of patients with Parkinson's disease. PMID- 2246662 TI - Paramedian thalamic and midbrain infarcts associated with palilalia. AB - A patient with paramedian thalamic and midbrain infarcts developed palilalia. PMID- 2246664 TI - Carotid dissection: a new false localising sign. PMID- 2246665 TI - Pure optic ataxia associated with a right parieto-occipital tumour. PMID- 2246666 TI - Palatal myoclonus successfully treated with clonazepam. PMID- 2246667 TI - Body building and rhabdomyolysis. PMID- 2246668 TI - Meningioma mimicking fibrous dysplasia of the skull. PMID- 2246669 TI - Disappearing CT lesions in Indian patients with epilepsy. PMID- 2246670 TI - Possible benign intracranial hypertension and essential thrombocythaemia. PMID- 2246671 TI - The lacunar hypothesis. PMID- 2246672 TI - The evaluation of diastolic function in arterial hypertension: how and why? PMID- 2246673 TI - Microalbuminuria in diabetes: which method to employ, which sample to collect. PMID- 2246674 TI - Cushing's syndrome: new variants and association with empty sella syndrome. AB - In this article we propose a review of the literature on clinical variants of Cushing's syndrome (CS) and personal observations on one of these variants. Clinical variants of CS are: (1) tumors of the intermediate pituitary lobe; (2) hypothalamic Cushing's with pituitary hyperplasia; (3) cyclic CS; (4) primitive nodular adrenal dysplasia; (5) pre-Cushing's syndrome; (6) association of CS and empty sella. The personal observations relate to the association of CS and empty sella. This syndrome consists of: (a) inappropriate cortisol secretion of pituitary origin; this alteration is less pronounced in comparison with other patients affected by Cushing's disease; (b) marked hirsutism; (c) slight hyperprolactinemia or augmented PRL response after metoclopramide; (d) elevated DHEAS levels. PMID- 2246675 TI - Thyroid carcinoma with biphasic clinical course and evolution in medullary carcinoma-follicular variant. A case report and an immunocytochemical demonstration of calcitonin and thyroglobulin in the same neoplastic cells. AB - The authors present an unusual case of thyroid neoplasia firstly diagnosed as an anaplastic carcinoma with no rise in plasma thyroglobulin (Tg) and treated with total thyroidectomy and radioiodine administration. After 18 months regional lymph node metastases were present with a rise in plasma calcitonin (Ct) (8000 14000 pg/ml); lymphectomy and external radiation were performed and histology revealed a metastasis from thyroid medullary carcinoma. After 3 years, mediastinal and right supraclavicular masses were present with a concomitant rise in plasma calcitonin (from 700 to 3400 pg/ml); all neoplastic lesions showed radioiodine uptake and plasma Tg was 8.9 ng/ml. A biopsy of the supraclavicular region was taken and 131I therapy was attempted, but the patient died after 6 months. Immunocytochemistry of the biopsy revealed the presence of a medullary carcinoma-follicular variant: the neoplastic cells were variably reacting with anti-Ct and anti Tg, and, moreover, the two antigens were sometimes observed in the same cell bodies. The metabolic pattern and the clinical course of this tumour are discussed, and the authors propose that Ct and Tg plasma levels be evaluated and a total body scan (WBS) with radioiodine be performed in all cases of medullary or poorly differentiated thyroid carcinomas. PMID- 2246677 TI - Preadsorption of radiolabeled monoclonal antibodies to liver and spleen tissues leads to higher tumor-to-normal-tissue ratios. AB - This study addresses the impact of background activity on the use of radioimmunoconjugates for radioimmunodiagnosis and radioimmunotherapy. Since the liver and the spleen represent organs with preferential nonspecific uptake, we exposed radiolabeled (iodinated and Indium-111 labeled) preparations of monoclonal antibodies to a suspension of fresh liver and spleen cells at physiological temperature and compared their immunoreactivity, in vivo biodistribution, and tumor targeting to those of the same radiolabeled proteins without prior adsorption to this suspension. The biodistribution studies were performed under conditions of high background activity, i.e., shortly after the injection (1 hour) and using a high dose of the protein. Preadsorption of radiolabeled monoclonal antibodies results in a significant decreased uptake in certain normal tissues, i.e., greater contrast between normal and tumor tissues, as demonstrated by the quotient of the two target-to-nontarget ratios (exposed/unexposed antibody) which was greater than one for most of the tissues examined. PMID- 2246676 TI - Evaluation of TAG-72 as a serum marker in ovarian and breast carcinoma. AB - Tumor Associated Glycoprotein 72 (TAG-72) is common to most epithelial tumors. In this study serum levels of TAG-72 were measured in 36 healthy female subjects, in 94 patients with breast cancer, and in 43 others with epithelial ovarian cancer. More particularly, 27 out of the 94 patients with breast cancer had early disease (Stage I-I; or T 0-2b; N 0-1b; M 0), while the remaining 67 had advanced disease (Stage III-IV; or T 0-4; N 0-3; M 0-1). All the 43 subjects with ovarian cancer were at stage III-IV (FIGO Classification), 12 of whom had minimal disease (lesions less than 2 cm) and the other 31 had bulky disease. 3.5 U/ml being the highest value found in the control group, we arbitrarily assumed 3.85 U/ml (mean +/- 3 SD) as the cut-off limit in this preliminary study. Among the patients with breast cancer, 17 out of the 67 subjects with advanced disease (25.3%) and 1 out of the 27 others with early disease (3.7%) exceeded the TAG-72 cut-off limit. Among the patients with ovarian cancer, 2 out of the 12 subjects with minimal disease (16.7%) and 22 out of the others 31 with bulky disease (70.9%) had TAG-72 levels above cut-off limit. High TAG-72 levels were found in all the histotypes of ovarian cancer including the mucinous type. Preliminary data seem to indicate that in ovarian cancer variations in serum levels of TAG-72 are in agreement with the trend of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246678 TI - Thyroid function after prolonged treatment for congenital hypothyroidism. PMID- 2246679 TI - Effect of dietary phosphorus in preterm infants. PMID- 2246680 TI - Appropriate use of growth hormone. PMID- 2246681 TI - More on aluminum toxic effects in children with uremia. PMID- 2246683 TI - Clues to the electrocardiographic diagnosis of subtle Wolff-Parkinson-White syndrome in children. AB - The electrocardiographic diagnosis of Wolff-Parkinson-White syndrome (WPW) may be missed because delta waves can be subtle in children, so we examined 66 electrocardiograms from patients with proven WPW, 24 from those with questionable WPW ("subtle WPW"), and 369 consecutive electrocardiograms from control patients to identify additional clues that WPW might be present. Three features were notable in WPW: no Q wave in left chest leads (88%), PR interval less than 100 milliseconds (80%), and left axis deviation (33%). In subtle WPW these findings were similar: 79%, 67%, and 46%, respectively. By comparison, 5% of control subjects had no Q wave, 16% had a PR interval of less than 100 milliseconds, and 4% had left axis deviation (all p less than 0.001). The coexistence of two of these features was common (74%) in WPW and subtle WPW (63%) but rare (2%) in control subjects (p less than 0.001). A PR interval of less than 100 milliseconds was less specific before 1 year of age, but 89% of patients with WPW had a QRS duration of greater than 80 milliseconds versus 2% of control subjects (p less than 0.001). Obvious WPW disappeared later in 11 patients; however, left axis deviation or lack of a Q wave persisted in eight (p less than 0.01). We conclude that the diagnosis of WPW in children, even when subtle, is suggested by the presence of these four changes. Preexcitation may persist in some patients in whom overt delta waves are no longer present. PMID- 2246682 TI - Liver disease in alpha-1-antitrypsin deficiency: prognostic indicators. AB - We reviewed the clinical presentation, subsequent course, and outcome of 98 patients with alpha 1-antitrypsin deficiency seen at our institution during the past 20 years to obtain answers to the following questions: (1) What prognostic factors aid in determining the course of liver disease in affected patients? (2) When is the appropriate time for referral to a liver transplant center? (3) Does breast-feeding prevent chronic liver disease? (4) What is the incidence of severe liver disease in family members? Our analysis revealed that the initial values of alanine aminotransferase, prothrombin time, and trypsin inhibitory capacity may have prognostic value. During clinical follow-up the recurrence or persistence of hyperbilirubinemia along with deteriorating results of coagulation studies indicated the need for liver transplantation because of imminent poor outcome. Girls had a worse prognosis than boys. Initial breast-feeding versus feeding of commercial formulas did not influence overall overcome. The incidence of significant liver disease among "at risk" siblings was 21% (3/14); if one assumes mendelian inheritance from heterozygous parents, the overall risk for siblings in our families was 5%. PMID- 2246684 TI - Sudden infant death syndrome in infants of substance-abusing mothers. AB - A population-based study was performed to determine whether substance abuse during the perinatal period may be a risk factor for sudden infant death syndrome (SIDS). The incidence of SIDS was studied in 2143 infants of substance-abusing mothers (ISAM) born in Los Angeles County during 1986 and 1987 who were reported to the Los Angeles County Department of Health Services because of a history of drug exposure or positive urine test results in the mother, infant, or both. By comparing the ISAM birth reports with records of autopsy-proven SIDS in Los Angeles County, we found 19 SIDS cases in the population of 2143 ISAM, a SIDS rate of 8.87 cases per 1000 ISAM (95% confidence interval 5.3 to 13.8). This was significantly higher than the SIDS rate for the non-ISAM general population: 396 SIDS deaths among 325,372 live births, an incidence rate of 1.22 cases per 1000 births, p less than 0.00001. The age of ISAM at death was 99 +/- 63 (mean +/- SD) days compared with 91 +/- 52 days for the non-ISAM population (not significant). The incidence of SIDS was significantly greater in male infants, during the winter months, in black infants, and in non-Hispanic white infants in the non ISAM population. Such differences were not observed in the ISAM group. A greater incidence of symptomatic apnea was reported before SIDS for the ISAM than for the non-ISAM population (22% vs 5.4%, p = 0.022). We conclude that ISAM have a higher incidence of SIDS than the non-ISAM general population. However, it was not possible to separate maternal substance abuse from other confounding variables that may also have had an impact on SIDS risk in the ISAM group. PMID- 2246685 TI - Value of a multiantigen radioallergosorbent test in diagnosing atopic disease in young children. AB - The purpose of this study was to investigate the value of a new multiantigen radioallergosorbent test, Phadiatop Paediatric, in the diagnosis of atopy in children less than 7 years of age. The diagnosis of atopic disease was established by history, physical examination, total serum IgE concentration, and the results of prick skin tests or radioallergosorbent tests or both, and then compared with the result of the Phadiatop Paediatric test for each patient. One hundred two patients (62 boys) between the ages of 4 months and 7.3 years were enrolled (median age 3.2 years). After the history and physical examination, 42% of the patients were believed to be atopic and 32% to be nonatopic; the diagnosis was uncertain in 26%. Skin prick test reactions to a variety of foods and inhalants were positive in 41 of 63 children tested; results of radioallergosorbent tests were positive in 35 of 61 children. Overall, atopy was diagnosed in 53 children and 49 were found to be nonatopic. When the clinical diagnosis was used as the gold standard, the Phadiatop test resulted in a correct diagnosis of atopy in 49 of 53 cases and of no atopy in 43 of 49 cases: sensitivity = 92%, specificity = 88%, and efficiency = 90%. Although the Phadiatop Paediatric test does not indicate specific sensitivities, it provides the clinician with a useful screening test for atopic disease in children 7 years of age or less, and the researcher with a means of validating atopic populations. PMID- 2246686 TI - Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction. AB - To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height. PMID- 2246687 TI - Late-onset ornithine transcarbamylase deficiency in male patients. AB - We report on 21 male patients who presented after 28 days of age with ornithine transcarbamylase (OTC) deficiency, which we define as late-onset OTC deficiency. These patients appeared normal at birth, but irritability, vomiting, and lethargy, which were often episodic, later developed. The age at presentation ranged from 2 months to 44 years. Biochemical testing revealed hyperammonemia, hyperglutaminemia, hypocitrullinemia, increased urinary orotate excretion, and decreased liver OTC activity measured in vitro, which ranged from 0% to 15% of normal. Male patients who were older at presentation had a somewhat different pattern of presenting symptoms and were more likely to die. These data illustrate the phenotypic variability of OTC deficiency. Unexplained episodes of repetitive or protracted vomiting in association with progressive alterations in behavior or neurologic findings should suggest the diagnosis of a urea cycle defect (or another symptomatic inborn error of metabolism), regardless of the age or medical history of the patient. PMID- 2246688 TI - Cocaine, sudden infant death syndrome, and home monitoring. PMID- 2246689 TI - Oximetry and peak expiratory flow in assessment of acute childhood asthma. PMID- 2246690 TI - Association between prenatal cocaine exposure and sudden infant death syndrome. PMID- 2246691 TI - Severe intravascular hemolysis in an infant with cyanotic congenital heart disease: resolution of hemolysis after repair. PMID- 2246692 TI - Plasma riboflavin concentrations in infants fed human milk versus formula: comparison with values in rats made riboflavin deficient and human cord blood. PMID- 2246693 TI - Endocrinopathies in Cornelia de Lange syndrome. PMID- 2246694 TI - Prenatal treatment of a patient with vitamin B12-responsive methylmalonic acidemia. PMID- 2246695 TI - Longitudinal study of neutrophil adherence and motility. PMID- 2246696 TI - Successful treatment of autoimmune enteropathy with cyclosporine. PMID- 2246697 TI - Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: a double-blind, randomized, placebo-controlled, multihospital trial. AB - To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation. PMID- 2246698 TI - Improved outcome at 28 days of age for very low birth weight infants treated with a single dose of a synthetic surfactant. AB - Two identical double-blind, controlled, randomized trials were initiated to determine whether the administration of a single 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal), soon after the delivery of infants with birth weights 700 to 1350 gm, would improve rates of survival without bronchopulmonary dysplasia. Both trials were terminated before enrolling their planned sample sizes because of the availability of Exosurf under the provisions of a Treatment Investigational New Drug program. We report the combined results of these trials. Study infants were stratified according to birth weight and gender before random assignment to a treatment regimen. One hundred ninety-two infants received Exosurf and 193 received an air placebo. The study groups were similar when a variety of demographic features describing the mothers, their pregnancies, the circumstances of the births, and the infants were compared. Exosurf-treated infants required significantly less oxygen and respiratory support during the first 3 days of life in comparison with the air-treated infants. Fewer infants in the Exosurf group had pulmonary interstitial emphysema (26 vs 13; p = 0.028). In the Exosurf group, there was a significant reduction in the combined outcome, neonatal death or survival with bronchopulmonary dysplasia (57 vs 39; p = 0.042), and there was a significant increase in rates of survival without this disease (128 vs 137; p = 0.042). There were no differences between treatment groups in the incidences of a variety of complications of prematurity, including apnea, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. We conclude that improvements in respiratory physiology after a single prophylactic dose of Exosurf result in an increased likelihood of neonatal survival without bronchopulmonary dysplasia. PMID- 2246699 TI - Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. AB - To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed. PMID- 2246700 TI - Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production. AB - In a prospective study, levels of interleukin-1 beta (IL-1 beta), interleukin-6) (IL-6), and tumor necrosis factor (TNF) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays, and were correlated with the clinical courses of the infants, including type of delivery and perinatal complications. Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries (142 +/- 68 pg/ml) or urgent cesarean section (290 +/- 21 pg/ml; both p less than 0.05 compared with normal deliveries). The IL-1 beta levels were elevated in infants with severe perinatal complications (282 +/- 116 pg/ml; p less than 0.001), whereas TNF and IL-6 levels were not related to these complications. Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection (p less than 0.001). In contrast, TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone (both p less than 0.05). These studies suggest that the levels of IL-1 beta, IL-6, and TNF in the cord plasma relate differentially to clinical complications in the perinatal period. PMID- 2246701 TI - Role of furosemide therapy after booster-packed erythrocyte transfusions in infants with bronchopulmonary dysplasia. PMID- 2246702 TI - Infectious diseases in the neonate: diagnosis and monitoring by quantitative plasma polymorphonuclear leukocyte-elastase determination. PMID- 2246703 TI - Enhanced hepatic drug clearance in patients with cystic fibrosis. AB - To examine whether hepatic drug metabolism is altered in patients with cystic fibrosis (CF), we evaluated the pharmacokinetics of three model pharmacologic substrates (antipyrine, a marker of hepatic oxidative metabolism; lorazepam, a marker of hepatic glucuronosyltransferase activity; and indocyanine green (ICG), a marker of hepatic blood flow and biliary secretion) in 14 patients with CF (14.6 to 29.2 years of age) and in 12 children and adolescents with cancer (7.2 to 19.4 years of age), which was treated with only surgery and radiation. Each study subject received a single intravenous dose of the combined model substrates (0.03 mg/kg lorazepam, 10 mg/kg antipyrine, and 0.5 mg/kg ICG) for 5 minutes, followed by repeated blood sampling (n = 10) during a 24-hour postinfusion period. Patients with CF had a significantly greater plasma clearance of lorazepam (56.5 +/- 5.2 vs 25.9 +/- 1.9 ml/min/m2) and ICG (892.5 +/- 176.4 vs 256.5 +/- 41.7 ml/min/m2) but not of antipyrine (27.2 +/- 3.8 vs 20.7 +/- 2.0 ml/min/m2) in comparison with control subjects. The apparent steady-state volume of distribution for lorazepam, ICG, and antipyrine was significantly higher in the patients with CF (2.0-, 3.1-, and 1.4-fold, respectively) than in control subjects. Clearance of the model substrates did not correlate with standard biochemical markers of hepatic function. Similarly, no significant relationships were observed between the clearance or steady-state volume of distribution of the compounds and the National Institutes of Health prognostic scores for the patients with CF. These data demonstrate that the plasma clearance of lorazepam and ICG is increased in patients with CF and suggest that hepatic glucuronosyltransferase activity and biliary secretory capacity are enhanced in this disease. PMID- 2246704 TI - Effect of continuous-infusion zidovudine therapy on neuropsychologic functioning in children with symptomatic human immunodeficiency virus infection. AB - Neuropsychologic function was assessed in 13 children with symptomatic human immunodeficiency virus disease (Centers for Disease Control Class P2), ranging in age from 14 months to 12 years. Before the initiation of treatment, eight patients were classified as having encephalopathy. Psychologic tests were administered both before and after 6 and 12 months of continuous-infusion azidothymidine (AZT; zidovudine) treatment. After 6 months of treatment a significant increase of 15.5 (+/- 3.3) IQ points was demonstrated in general cognitive functioning (p less than 0.001). Follow-up for 10 of these patients indicated that after 12 months of AZT therapy, they had maintained their gains in IQ points. Improvements in adaptive behavior after 6 months of therapy, assessed with a standardized interview, paralleled the findings on the IQ data. No significant differences in the amount of change was observed for the different subgroups. The magnitude of these improvements could not be explained by practice effects, environmental changes, or general improvement in physical state. We conclude that neuropsychologic function was significantly improved with continuous infusion AZT treatment. PMID- 2246706 TI - Omeprazole treatment of severe peptic disease associated with antral G cell hyperfunction and hyperpepsinogenemia I in an infant. PMID- 2246707 TI - Advances in pediatric pharmacokinetics and therapeutics. PMID- 2246705 TI - A prospective, randomized, double-blind comparison of calcium chloride and calcium gluconate therapies for hypocalcemia in critically ill children. PMID- 2246708 TI - Rice as a carbohydrate substrate in oral rehydration solutions (ORS). PMID- 2246709 TI - Cows' milk during the second half-year of life--effect on iron status. PMID- 2246710 TI - Dependability of esophageal pH-monitoring data in infants on cutoff limits: the oscillatory index. AB - The cutoff limit for pathologic gastroesophageal reflux (GER) has been arbitrary, although generally accepted determined at pH 4.00. The influence of a small pH error (0.25 pH units above or below pH 4.00) was analyzed in 173 consecutive pH monitorings. This appeared to cause a misinterpretation of the data in 51 of 173 infants (29%). We propose the introduction of a new parameter measuring the percent of time of the total investigation that the recorded pH varies between 4.25 and 3.75: the "oscillatory index" (OI). The index ranged from 0-42%. The higher the OI, the more pH data that are recorded between pH 4.25 and 3.75. The OI is related to the arbitrary aspects of a boundary level. The Pearson correlation coefficient between the percent of time of the investigation the pH was less than 4.00 and the OI was 0.75. If an OI of more than 10% in infants with normal pH-monitoring data of more than 15% in infants with a GER pathology would be considered as abnormal, pH-monitoring data of 45 infants should be considered for reclassification (26%). Prior to general application, this parameter should be evaluated by more centers in different patient populations, and other "oscillatory ranges" should be analyzed. PMID- 2246711 TI - Helicobacter pylori infection and chronic gastritis: clinical, serological, and histologic correlations in children treated with amoxicillin and colloidal bismuth subcitrate. AB - Twenty-three children with Helicobacter (Campylobacter) pylori-associated chronic gastritis are reported. Family history of peptic disease, previous digestive procedures, and nonspecific epigastric pain were the most frequently encountered clinical features. Antral nodularity at endoscopy and histologic evidence of follicular gastritis were characteristic morphological aspects. Rapid urease tests suggested the diagnosis in 90% of patients. Significant increases of serum IgG and IgA against Helicobacter pylori allowed the identification of infected children with 95% cumulative sensitivity. Treatment with amoxicillin and bismuth subcitrate eradicated the infection and improved gastritis in 13 of 19 children. These findings provide further evidence for the etiologic role of Helicobacter pylori in chronic antral gastritis in children. PMID- 2246712 TI - Prevention of neonatal necrotizing enterocolitis. AB - Small premature infants are often hypochlorhydric, and frequently their stomachs are colonized by enteric, gram-negative bacteria. We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis. A prospective, double-blind study was conducted that compared a group of infants supplemented with 0.01-0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water. Gastric pH, gastric enteric bacteria counts, and the incidence and severity of necrotizing enterocolitis were monitored. The median gastric pH of the HCl-supplemented group was lower (3.0) than controls (4.0) throughout the study (p less than 0.001). The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 (p less than 0.001). Somatic growth rates in infants in the HCl-supplemented group were equal to, or exceeded, those in the control group. There was 1 case of necrotizing enterocolitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group (p = 0.02). It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of necrotizing enterocolitis. PMID- 2246713 TI - Growth acceleration and final height after treatment for delayed diagnosis of celiac disease. AB - The only presenting clinical feature of diagnosing celiac disease (CD) late may be short stature. At the start of treatment with a gluten-free diet (GFD), celiac children show an accelerated growth rate. The real duration of catch-up growth and influence of diet on the final stature has not yet been defined. In order to evaluate the effect of a GFD on growth parameters, 24 children diagnosed late with CD were studied at our center. During the period of diagnosis, weight, height standard deviation score (HSDS), weight and height velocities (WV and HV), bone age (BA), and pubertal stage were recorded. Predicted height (PH) according to the Tanner method, parental height, and target height (TH) were also evaluated at diagnosis. All patients initially presented because of short stature or retarded growth (100% of patients with height less than 5th percentile). Patients showed an increased HV and WV during the first 3 years on a GFD, with maximum growth velocity occurring during the first year, but the catch-up growth was incomplete over 3 years (mean HSDS +/- SD, -1.77 +/- 0.6). Puberty began in all patients at a normal age. The 12 patients who completed pubertal development reached their target height, whatever the duration of the GFD. The final height (between the 1st and 25th percentile) seemed influenced mainly by familial characteristics; height was below the 3rd percentile in 31% of parents examined. PMID- 2246715 TI - A dot immunobinding assay to detect anti-alpha-gliadin antibodies in celiac disease. AB - A dot immunobinding assay to detect anti-alpha-gliadin-specific antibodies in the sera or whole blood of enteropathic patients is described here. The method is based on the adsorption of alpha-gliadin as a spot onto nitrocellulose sheets. After incubation with the patient sample, the detection of specific antibodies is performed with alkaline phosphatase-conjugated goat anti-human (IgA or IgG) antibodies. Twenty-one celiac serum samples together with 18 enteropathic or disease controls and 44 healthy controls were analyzed. The classical ELISA test and the dot test gave comparable results. The dot test gave reliable result even when whole blood was tested. The method proved to be simple and sensitive. PMID- 2246714 TI - Beta 2-microglobulin levels in celiac disease. AB - The serum levels of beta 2-microglobulins (beta 2-m) were studied in 65 celiac children. Significant statistical differences (p less than 0.05) were found between the values of patients on a gluten-containing diet (mean +/- SD, 1.92 +/- 0.64 mg/L) and those on a gluten-free diet for less than (mean +/- SD, 2.38 +/- 0.76 mg/L) or greater than (mean +/- SD, 1.46 +/- 0.77 mg/L) 8 months. A significant difference was also found between the first group and the 15-subject control group, who underwent intestinal biopsy for low stature or chronic diarrhea but had normal intestinal mucosa (mean +/- SD, 1.56 +/- 0.42 mg/L). Serum beta 2-m levels were above normal values (less than 2 mg/L) in 10 of 26 (38.5%) celiac patients on a gluten-containing diet and in two of 15 (13.3%) subjects of the control group. The beta 2-m values of patients on a gluten-free diet for less than or equal to 8 months were significantly different (p less than 0.001) from those of patients on a gluten-free diet for greater than 8 months, as well from those of the control group. No significant differences were found between patients on a gluten-free diet for greater than 8 months and the control group. A significant correlation between the antigliadin antibody (AGA) IgA and beta 2-m in the patients on a gluten-free diet for greater than 8 months and control-group patients was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246716 TI - Normal energy intake range in children with chronic nonspecific diarrhea: association of relapses with the higher level. AB - An increase in energy intake often occurs at weaning. The increase may be due partly to prompting by the caregiver to accelerate the child's weight gain and partly motivated by the palatability of common weaning foods. Increased food intakes initiated during weaning and continued into the second year of life may be associated with chronic, nonspecific diarrhea in selected children. An educational project was designed to reduce intakes augmented by either cause. Reductions were achieved by the regulation of energy-dense foods in the child's diet and reliance on the child's appetite control to determine meal size. The educational intervention was applied prospectively under nonblinded, controlled conditions. Children, 1 to 2 years of age, with chronic nonspecific diarrhea were assigned randomly to either a treatment or control group. Compliance, food consumption, preprandial glycemia, and outdoor activities were reported by the children's mothers in four 7-day diaries; symptoms related to the children's clinical condition and anthropometric and biochemical indices of nutritional status were noted at the beginning and end of a 7-month period. Forty-four of 53 children in the experimental group maintained compliance, and 44 of 47 children in the control group completed the follow-up. Energy intake decreased significantly by almost one-third in the experimental group. Growth, skinfold thickness measurements, and outdoor activities were similar between experimental and control groups over the 7-month period. Diarrheal episodes occurred in 6, 1, and 2 children in the experimental group at 1.5, 3, and 7 months and in 22, 18, and 15 children in the control group, respectively (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246717 TI - Vitamin B12 and folic acid absorption and hematological status in children with postenteritis enteropathy. AB - In a group of nine children with postenteritis enteropathy (i.e., persisting small-intestinal mucosal damage and failure-to-thrive after an acute episode of gastroenteritis), absorption capacities for vitamin B12 and folic acid were studied and compared with hematological status in peripheral blood. The fractional absorptions of vitamin B12 (FAB12) and folic acid (FAFol) were determined by means of a double-isotope technique employing a single-stool-sample test. The children were examined when growth retardation was maximal, and examinations were repeated during the late recovery period. In spite of considerable small-intestinal mucosal damage, only the absorption of vitamin B12 was markedly affected, while that of folic acid was almost intact. When growth retardation was maximal, FAB12 was below the normal age-correlated range in half of the children. FAB12 was also severely reduced in all longitudinally observed children when compared with the results obtained during the late recovery period (p less than 0.005). FAFol was below the normal range in one fourth of the children, but the reduction was modest and insignificant when compared with the results of repeated examinations during the late recovery period. A moderate iron deficiency was detected in half the children. High levels of plasma vitamin B12, folic acid, and erythrocyte folate were detected at both early and later examinations, indicating that these parameters were not affected by the reduced absorption capacities. However, if malabsorption and chronic diarrhea are combined with low dietary intake of vitamin B12, as is the case for many children in the Third World, depletion of vitamin B12 stores may result. PMID- 2246718 TI - The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake. AB - During the decade from 1976 to 1986, the age-related incidence of meconium ileus equivalent (MIE) was calculated on the basis of 240 Danish cystic fibrosis (CF) patients. In the first 5 years, the patients were given enteric-coated granules of pancreatic enzymes (Pancreatin, Rosco, Denmark), and a low fat diet was recommended. In the last 5 years, the Center recommended supplementation with acid-resistant, enteric-coated, encapsulated microspheres (Pancrease, Cilag, Birkerod, Denmark), and high-energy intake with a 40% fat content and no dietary restrictions. There was no difference in the incidence of MIE when these two 5 year periods were compared, and the overall incidence of MIE was low (5.4 MIEs/1,000 patient years). This may, at least in part, be due to the rather high intake of exocrine pancreas enzyme supplementation (EPES) (a mean intake of 0.9 capsules/kg/day). MIE occurred almost exclusively among patients greater than 15 years old and peaked in young adults aged 20-25 years (35.5 MIEs/1,000 patient years). The daily intake of EPES/kg of body weight declined significantly with age, and the patients who developed MIE received even less than average per day. Both of these points strengthen the view that a low enzyme dosage is likely to have an effect on the incidence of MIE. PMID- 2246719 TI - Variations in oligosaccharides and lactose in human milk during the first week of lactation. AB - Variations in oligosaccharides and lactose in human milk were studied in 15 mothers during the first week of lactation. The neuraminyloligosaccharides and heavy neutral oligosaccharides increased slightly from days 2 to 5 postpartum and appeared to decrease until day 7. The lacto-N-difucohexaoses, lacto-N fucopentaoses, and lacto-N-tetraose increased until day 5 and then decreased. Lactodifucotetraose and the fucosidolactoses decreased substantially until day 5 (p less than 0.05) and appeared to stablize in the following days. Lactose increased until day 5 (p less than 0.05) and continued to increase thereafter. Lactose was negatively correlated with total oligosaccharides (p less than 0.10). The fluctuations observed in total oligosaccharides from days 2 to 5 postpartum and their subsequent stabilization and regular decrease during lactation confirm the hypothesis of Kulski and Hartmann that mammary secretion occurs in three periods: colostrum for the first 36 h postpartum, transitional milk from days 2 to 5 postpartum, and mature milk after day 5. The oligosaccharide variations we found corresponded to those of other milk constituents observed by other authors. The significance of the oligosaccharide variations is discussed. PMID- 2246720 TI - Discriminant carbohydrate components of human milk according to donor secretor types. AB - Because of the variability of human milk carbohydrate composition, we determined the discriminant carbohydrate components of the milk of 18 mothers according to their ABH and Lewis secretor types during the first week of lactation. Comparative chromatograms revealed that the presence of neuraminyloligosaccharides is linked to the ABH secretor groups, and that the absence of oligosaccharides with Lea or Leb specificity is linked to the Lewis nonsecretor types. The study of carbohydrate composition according to donor secretor types consisted of measuring 16 variables from 69 samples. Analysis of variance showed significant differences between groups: high levels of N acetylneuraminic acid and low levels of galactose distinguished ABH secretors from nonsecretors (p less than 0.001). In the ABH secretor groups, A and H secretors had higher N-acetylglucosamine contents than B and AB secretors (p less than 0.001) and lower galactose levels (p less than 0.001). The Lewis secretor groups were distinguished by significantly higher fucose levels (p less than 0.001). The ABH(+)Le(a-b-) group had higher lactose contents than the other groups (p less than 0.01). PMID- 2246721 TI - Serum carnitine and nutritional status in children treated with continuous ambulatory peritoneal dialysis. AB - The serum carnitine (total carnitine), total protein, amino acid, and triglyceride levels were determined in children on continuous ambulatory peritoneal dialysis (CAPD). Compared with levels in controls, serum carnitine levels were significantly decreased in patients on CAPD for more than 4 months, while those of patients on CAPD for 1-3 months were not decreased. Patients on CAPD for more than 4 months also showed lower serum total protein levels than in normal controls. The mean triglyceride levels in patients on CAPD for both 1-3 months and more than 4 months were higher than those in normal controls. Among the amino acids, the serum levels of tryptophan, isoleucine, leucine, tyrosine, valine, serine, and asparagine were significantly lower in patients treated with CAPD than in normal controls, whereas the levels of other amino acids were either increased or not changed. Isoleucine and leucine levels showed a strong correlation with serum carnitine. Our data suggest that malnutrition plays a role in the decrease of serum carnitine levels in patients receiving CAPD. PMID- 2246722 TI - Pediatric HBsAg chronic liver disease and adult asymptomatic carrier status: two stages of the same entity. AB - Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of greater than 10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using alpha fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14% anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma. PMID- 2246723 TI - Enhanced sodium absorption by citrate: an in vivo perfusion study of rat small intestine. AB - The effect of citrate on sodium, potassium chloride, and water absorption in the presence of glucose from the whole rat small intestine was studied by an in vivo marker perfusion technique. The perfusion solutions contained glucose and were similar in their electrolyte composition to the currently recommended oral rehydration solution for the treatment and prevention of diarrheal dehydration. Significantly more sodium and water absorption occurred from the citrate containing solution than from the one without citrate. It is concluded that citrate enhances net sodium absorption from a glucose electrolyte solution in the rat small intestine independent of glucose-stimulated absorption. PMID- 2246724 TI - Food proteins and maturation of small intestinal microvillus membranes (MVM). III. Food protein binding and MVM proteins in rats from newborn to young adult age. AB - To investigate postnatal maturational profiles of functional and biochemical properties of rat small intestinal microvillus membranes (MVM), we did a longitudinal study in rats from birth to the age of 12 weeks. In parallel, we studied binding of cow's milk proteins and of the wheat gliadin peptide B 3142, as well as MVM proteins (SDS-PAGE). Changes in MVM fluidity and lipid composition exhibited early (0-4 weeks) and intermediate and late (6-12 weeks) patterns, as has been published earlier. Postnatal changes of food protein and peptide binding occurred early during the observation period, not related to weaning. There was not much further change in binding after 6-8 weeks. Developmental profiles of MVM protein and some lipid changes resembled, but did not equal, changes in food protein binding. We conclude that changes in MVM biochemical composition affect MVM binding characteristics. In particular, high molecular weight MVM proteins (susceptible to trypsin treatment) appear to play a role in postnatal maturational differences in MVM food protein binding. PMID- 2246725 TI - Hypertransaminasemia as the first symptom in infant celiac disease. AB - Two infants admitted for evaluation of hypertransaminasemia had high levels of anti-gliadin IgA and IgG antibodies and histological changes of the duodenal mucosa typical of celiac disease. Although the cause of the liver involvement could not be exactly identified, both the hypertransaminasemia and the histological changes of the mucosa disappeared after a short period of gluten free diet. Even though two cases are not enough for definite conclusions, the authors suggest that an unexplained increase in transaminases would require an evaluation for celiac disease. PMID- 2246726 TI - Neonatal duodenal perforation. AB - Duodenal perforation in neonates is uncommon, and has been described rarely in the third part of the duodenum. Gastrointestinal perforations without an obvious cause have been labeled as "spontaneous." We report a case of perforation in the third part of the duodenum in a premature infant for which there was no obvious cause. In such "spontaneous" perforations, multifactorial etiology is likely and possible factors are discussed. The high mortality rate in such patients can be improved by early diagnosis and prompt resuscitation followed by surgery. Peritoneocentesis plays an important diagnostic role. It is also therapeutic in relieving the respiratory distress caused by free intraperitoneal air. The majority of duodenal perforations are amenable to primary closure at surgery and this should be the treatment of choice. PMID- 2246728 TI - Severity scoring system for infantile gastroenteritis. PMID- 2246727 TI - Enterocolonic fistula due to incarcerated inguinal hernia. AB - A 2 1/2-year-old boy presented severely underweight and with an extremely distended abdomen. He was born prematurely and at age 6 months had an incarcerated inguinal hernia, which had been treated conservatively. Laboratory investigations at the time of presentation showed evidence of bacterial overgrowth. Barium studies revealed a fistula between the jejunum and sigmoid colon. Resection of the fistula was followed by complete recovery. We suggest that the incarcerated hernia underlies this fistula. Until now, this series of events has not been published. PMID- 2246729 TI - Long-term use of cisapride (prepulsid) in premature neonates of less than 34 weeks gestational age. PMID- 2246730 TI - Evaluation of neonatal cholestasis. PMID- 2246731 TI - Hereditary pancreatitis: report of the second kindred in Italy. PMID- 2246732 TI - Lactose-intolerance and hypolactasia in children with giardiasis. PMID- 2246733 TI - Pars plicata lensectomy/vitrectomy for developmental cataract extraction: surgical results. AB - Fifty-two cases of developmental cataracts extracted using the pars plicata lensectomy/vitrectomy technique were reviewed. Eyes with additional ocular anomaly other than microphthalmos were not included. No early complications were detected in a postoperative period ranging from 1.5 to 7 years with a median of 4 years, and late complications were limited to secondary membranes occurring in small eyes. Since secondary membranes occurred only in eyes in which the axial length was less than or equal to 17.4 mm and the corneal diameter was less than or equal to 9.5 mm, we suggest that eyes that are small by the absolute dimensions cited here are at greater risk of developing secondary membranes postoperatively. Small eyes by absolute dimensions should be distinguished from microphthalmic eyes, since the relative term microphthalmic is less predictive of risk of complication than are absolute dimensions. Linear Snellen acuity in 15 patients capable of response ranged as follows: 20/20-20/80 with a median of 20/40 in eyes with partial bilateral cataracts; 20/25-20/80 with a median of 20/50 in eyes with complete bilateral cataracts; 20/30-20/400 with a median of 20/200 in eyes with unilateral partial cataracts; and 20/60-CF with a median of 20/400 in eyes with complete unilateral cataracts. Mean patient ages at surgery were 3 months for those with bilateral complete cataracts, 5 months for those with unilateral complete cataracts, 18 months for those with bilateral partial cataracts, and 25 months for those with unilateral partial cataracts. The earliest possible removal of visually significant opacities must be combined with aggressive postoperative visual rehabilitation to obtain the best possible visual outcome. PMID- 2246734 TI - Bilateral consecutive superior oblique palsy following fronto-ethmoidal sinusitis. AB - A 61-year-old woman developed a left superior oblique palsy as a result of frontoethmoidal sinusitis. After stabilization, the left inferior oblique and right inferior rectus were recessed. Three years later, she developed a right superior oblique palsy associated with fronto-ethmoiditis. The right inferior oblique and left inferior rectus were recessed. PMID- 2246735 TI - Microspherophakia in association with the rhizomelic form of chondrodysplasia punctata. AB - Chondrodysplasia punctata is a multisystem disorder, primarily involving the musculoskeletal system, skin, and eyes. Children with the rhizomelic form of this syndrome have characteristic facies with a saddle-nose deformity, hypertelorism, and frontal bossing. The musculoskeletal changes include proximal limb shortening, flexion contractures, congenital hip dislocations, and the characteristic radiographic finding of epiphyseal stippling of the axial skeleton and long bones. The most common ocular findings are cataracts and optic atrophy. We describe herein the first reported case of microspherophakia in association with the rhizomelic form of chondrodysplasia punctata. PMID- 2246736 TI - Use of high dose chloral hydrate for ophthalmic exams in children: a retrospective review of 302 cases. AB - Although chloral hydrate sedation has been proposed as an alternative to evaluation under anesthesia for pediatric patients who are unable to cooperate with routine test procedures, a careful study of the drug's safety and effectiveness is lacking. This study reports the effectiveness and safety of high dose chloral hydrate for ophthalmic examination in 302 patients between the ages of 1 month and 5 years. The patients had nothing to eat or drink for 4 hours prior to drug administration. The patients were monitored during sedation and until fully awake. Eighty-eight percent of the patients (266/302) were successfully sedated without a supplemental dose. There were no reports of any complications including emesis, respiratory distress or depression, behavioral problems, changes in vital signs, patient injury, or hospital admission. The high dose chloral hydrate protocol described, results in safe and generally successful sedation of pediatric patients for ophthalmic examination. PMID- 2246737 TI - Near retinoscopy in accommodative esotropia. AB - We tested whether near retinoscopy, a noncycloplegic retinoscopic technique, was applicable to the optic correction of patients with accommodative esodeviations. We performed a study in 17 patients with accommodative esotropia to compare the refractive values obtained by near retinoscopy and by cycloplegia, as measured by two examiners. The interobserver variability was the same for the two techniques for the refractive values of the horizontal and vertical meridia and spherical equivalent. For the astigmatism, there was greater variability for near retinoscopy. The correlation between the two methods was good, but the variability of the differences was high. We recommend that near retinoscopy should be employed only as a noninvasive method for screening refractive errors in children. PMID- 2246738 TI - Head nodding associated with intermittent esotropia. AB - Head nodding (to-and-fro turning about the vertical cervical axis) associated with abnormal eye movements may be seen in spasmus nutans and congenital nystagmus. In the absence of abnormal eye movements, it may be indicative of neurological disease (eg, cerebellar disease, basal ganglia dysfunction). We report a neurologically normal infant without nystagmus but with intermittent head nodding and intermittent esotropia, whose head movements manifested only when his eyes were straight. The head movements ceased with the occlusion of either eye or spontaneous onset of esotropia. When his head was forcibly stabilized, he immediately developed esotropia. The head movement presumably facilitated fusion, although the mechanism of action is unknown. PMID- 2246739 TI - A unique epibulbar osseous choristoma. AB - The case of a 14-year-old girl found to have a unique epibulbar osseous choristoma attached to the sheath of the superior rectus muscle is recorded. The bony mass was palpable through the upper lid and by computerized tomography, it appeared densely calcified and noncystic. There was no ptosis or abnormality in ocular motility preoperatively or postoperatively. PMID- 2246740 TI - Endophytic vs exophytic unilateral retinoblastoma: is there any real difference? AB - A retrospective review of 297 cases of enucleated and histologically proven unilateral retinoblastoma with a minimum of 5-year follow-up was analyzed to see if there were any clinical or prognostic differences between endophytic and exophytic type retinoblastoma. Endophytic retinoblastoma (181 cases) was found more often than exophytic (116 cases). The following features were not associated with the clinical appearance of either endophytic or exophytic tumors: sex of patient, right vs left eye, propensity for bilateral development, initial sign or symptom, presence of rubeosis, preoperative metastasis, optic nerve invasion, orbital recurrence, survival of the patient, length of follow-up, or age at diagnosis. Three features were found that correlated with type: a disproportionately higher percentage of patients with endophytic retinoblastoma had a positive family history; a disproportionately high percentage of patients with exophytic retinoblastoma developed glaucoma; and choroidal invasion occurred significantly more often in patients who had exophytic retinoblastoma than in those who had endophytic retinoblastoma. PMID- 2246741 TI - Erroneous findings in polarized testing caused by plastic prisms. AB - Certain plastic prisms, when used with polarized tests (eg, stereopsis), can destroy the uniqueness of each eye's view. We investigated this effect by administering the Randot stereotest to 12 visually normal observers. The test was administered monocularly (simulating suppression), under habitual conditions, and through six representative prisms, both fused and monocularly. Whereas stereo thresholds with an anaglyphic random dot stereogram (TNO) were not significantly affected by the prism, fusing through some of the prisms resulted in significantly poorer stereo thresholds and a failure to detect random dot stereopsis (RDS) on the polarized stereotest. Furthermore, some subjects appreciated RDS viewing monocularly through each of the prisms. Thus, it is important to conduct polarized testing through prisms that are known not to interfere with polarization. This optical phenomenon is explained here. PMID- 2246742 TI - Stickler's syndrome in the Cleft Palate Clinic. AB - Stickler's syndrome is a much underdiagnosed entity in the ophthalmic population. It is a dominantly inherited disease of connective tissue whose ocular findings include moderate to severe myopia, vitreoretinal degeneration, retinal detachments, cataracts, and glaucoma. Non-ophthalmologic findings include cleft palate, midfacial hypoplasia, radiographic changes of spondyloepiphyseal dysplasia, narrow pelvis, and broad femoral neck. Twenty percent of patients with Stickler's syndrome will have a cleft palate. We undertook a study to determine the incidence of Stickler's syndrome in patients with an isolated cleft palate, and to see if this screening process would be useful in making an early diagnosis of the syndrome and in genetic counseling. It is important to distinguish this syndrome from that of isolated cleft palate in order to: 1) insure early detection of myopia and monitor for signs of retinal detachment, cataract, and glaucoma; and 2) provide definitive recurrence counseling for families (50% vs 2.3%). PMID- 2246743 TI - Retinopathy of prematurity: the relationship with intraventricular hemorrhage and bronchopulmonary dysplasia. AB - We studied prospectively a cohort of 326 neonates weighing 500-1250 gm at birth. These babies were all born at Magee-Womens Hospital during 1986 and 1987. Sixty five percent survived and were discharged from the hospital, and 197 of the survivors (93%) had at least one ophthalmological exam before their discharge. Of the patients who were examined, 34% had retinopathy of prematurity (ROP) and 12% had stage 3 or 4 ROP in at least one eye. There were six neonates with at least one blind eye, giving an estimated prevalence of blindness caused by ROP of 301 per million live births. By univariate analysis there was a strong association of ROP with birthweight, oxygen exposure, respirator treatment, and intraventricular hemorrhage (IVH). By multivariate analysis, only the respirator treatment was significantly associated with ROP. When birthweight, oxygen exposure, and IVH were controlled, a baby requiring more than 28 days of ventilator treatment was 4.07 times more likely to have stage 3 or 4 ROP than a baby with less ventilator exposure. These data confirm the strong association of ROP with bronchopulmonary dysplasia (BPD), low birth-weight, and IVH, and suggest that the key component among these interrelated variables may be time spent on a ventilator. PMID- 2246744 TI - The effect of topical cysteamine drops on reducing crystal formation within the cornea of patients affected by nephropathic cystinosis. AB - We studied the usefulness of topical cysteamine ophthalmic drops in reducing crystal formation within the corneas of patients affected by nephropathic cystinosis. A dosage of 0.3% cysteamine given four times daily was chosen as a more manageable method than a previously reported protocol of hourly administration of 0.11% drops. No reduction in crystal formation was observed in our patients; they were followed for seven months. PMID- 2246746 TI - The structured nonverbal assessment of personality. AB - This article describes the development of a structured nonverbal measure of personality based on Murray's (1938) system of needs. The items of the Nonverbal Personality Questionnaire consist of line drawings of a central figure performing trait-relevant behaviors in specific situations; respondents are asked to indicate the likelihood of engaging in similar behaviors. The nonverbal form was administered to three Canadian samples of respondents and one Finnish sample. Reliability and validity data for the initial item pool and for a revised form are reported. The utility of the nonverbal inventory for cross-cultural and theoretical work in personality is discussed. PMID- 2246747 TI - Adolescent adjustment and coping strategies. AB - This study examines the relation between psychosocial adjustment and coping strategies among college freshmen. Three hundred thirty-one college students completed the Inventory of Psychosocial Development (IPD; Constantinople, 1969) and the Adolescent Coping Orientation for Problem Experiences (ACOPE; Patterson & McCubbin, 1987) inventory. Factor analysis of the ACOPE scales revealed two factors interpreted to represent the coping strategies of "salutary effort" and "stress palliation." For each subject a relative salutary effort score was calculated to reflect the proportion of coping efforts ascribable to mature, salutary coping efforts. Optimal adjustment was associated with adolescents whose reported means of dealing with tension reflected a high proportion of salutary effort. These findings, which support the notion of a covariation between styles of coping and psychological adjustment among adolescents, are discussed in light of psychosocial development, coping, and methodological issues related to research on coping and adjustment. PMID- 2246745 TI - A diagnostic ruler for strabismus and amblyopia. AB - We designed a diagnostic slide ruler for easier detection of strabismus and amblyopia, both of which begin in childhood. This new instrument makes the Parks three-step test easier to use and faster than other methods in diagnosing isolated cyclovertical muscle paralysis. Furthermore, the slide ruler tests visual acuity with both series letters and single letters. Incorporated into the instrument are Laurence's strabismometer, Haab's pupillometer, occluder, pinhole, and millimeter ruler. A laboratory model is now available, and this slide ruler can assist the ophthalmological practitioner in analyzing three-step test data more rapidly than graphs and computer programs can. This instrument can also diagnose pediatric patients in the early stages of microstrabismus and amblyopia to obtain the best therapeutic results. PMID- 2246748 TI - Effect of multiple-dose irradiation on repair capacity in plateau phase C3H 10T1/2 cells. AB - Using plateau phase C3H 10T1/2 cells, we studied the effect of multiple-dose irradiation on the repair capacity of cells after further irradiation. Cells were irradiated with repeated doses of 2.5 Gy delivered two fractions per day at 6 to 7 hours interval. The cell survival after exposure to 1 to 9 fractions was lower above 5 fractions as compared to that predicted by calculating from single dose survival curve by assuming that cells retain their capacity to repair radiation damage after each fraction. Repair kinetics experiments showed that cells were less able to repair potentially lethal damage after test dose following multiple dose irradiations. There was, however, no difference in the ability to repair sublethal damage and potentially lethal damage sensitive to anisotonic treatment in preirradiated and untreated cells. Thus, it would appear that an enhancement of the lethal expression of potentially lethal damage of three types of damage may, at least in part, contribute to the difference between the cell survival curve after multiple fractions and that predicted by calculation. PMID- 2246750 TI - Acquired radioresistance after low dose X-irradiation in mice. AB - Low doses (2.5-15 cGy) of X-irradiation two months prior to a second exposure to a sublethal dose enhanced the survival rate in mice. Optimal and significant increase was observed with 5-10 cGy. Endogenous spleen colony counts (endo-CFUs) after 7 Gy increased by a factor of about 1.7 in mice pre-irradiated with 5-10 cGy, while the number of blood forming stem cells (CFUs) in the pre-irradiated group did not exceed that in the sham-irradiated control group at the period of the second exposure (two months after irradiation with 5 cGy). The low dose exposure seems to stimulate recovery of blood forming stem cells after the second irradiation and favors a decrease in the incidence of bone marrow death. PMID- 2246749 TI - The effect of ionizing radiation on epidermal Langerhans cells--a quantitative analysis of autopsy cases with radiation therapy. AB - Langerhans cells (LCs) are dendritic cells located in the epiderm is with antigen presenting capacities. We performed a quantitative analysis of LC density in the anterior chest skin of 286 autopsy cases, including 31 cases treated with radiation therapy. Skin specimens were stained by immunoperoxidase technique (PAP method) with an anti-S-100 protein antiserum. S-100 positive LCs were counted for comparison between non-irradiated and irradiated cases. In this study we noted that, 1) The decline in density of the LCs was age-related and dendritic processes were more prominent in younger groups. 2) The cases irradiated within one month before autopsy showed a reduction in LC density compared with age matched controls. 3) The cases irradiated more than one month before autopsy demonstrated no consistent or definite tendency. It is suggested that ionizing irradiation as well as ultraviolet light may deplete the LC density in an acute phase. The possibility that radiation therapy alters immunological surveillance in the human skin is discussed. PMID- 2246751 TI - The effect of external gamma-irradiation on 59Fe release in vitro from alveolar macrophages previously having ingested 59Fe-iron hydroxide colloid. AB - The effect of external gamma-irradiation on the digestive function of rat alveolar macrophages (AM) was studied by using the in vitro assay system, where the 59Fe release from AM engulfing 59Fe-iron hydroxide colloid was measured as an indicator of their digestive capability. Graded doses of gamma-irradiation up to 100 Gy had no effect on the extracellular release of 59Fe in AM cultured at 4 and 37 degrees C for 8-72 hrs postirradiation. When 10 mM Ca-DTPA was added to the culture medium, the 59Fe release was slightly depressed by irradiation at a dose of 30 Gy. It is apparent from these results that gamma-irradiation had no effect on the 59Fe transfer between cell and medium, and little effect on the catabolism of 59Fe-colloid in rat AM. PMID- 2246752 TI - Effects of long-term radiation exposure on chromosomal aberrations in radiological technologists. AB - Chromosomal aberrations in the lymphocytes of radiation technologists (RT) were analyzed by the trypsin G-banding method to study the late effects of long-term exposure to low doses of radiation. Structural aberrations were identified in 384 (2.5%) of 15,442 cells analyzed from 53 RT as compared to 177 (1.6%) of 11,136 cells from 36 healthy controls. Stable aberrations were the most frequent in both groups and were either translocations or deletions. Unstable aberrations were mainly acentric fragments in both groups. The frequency of translocations and acentric fragments was significantly higher in the RT than in the controls and was highest in the RT over 50 years. The highest frequency observed in the greater than 50 age group was attributed to the unknown for cumulative dose prior to introduction of film badges. Frequency of chromosomal aberrations correlated with the estimated dose from the film badges and years of experience of each RT based on the equation y = 0.22 + 0.37D + 4.35D2, where y is overall frequency of chromosomal aberrations and D is the estimated radiation dose in Sv. PMID- 2246753 TI - Incidence of skin cancer among Nagasaki atomic bomb survivors (preliminary report). AB - Among a total of 65,268 Nagasaki atomic bomb survivors recorded in the Scientific Data Center of Atomic Bomb Disaster, Nagasaki University School of Medicine, 140 cases with skin cancer were collected from 31 hospitals in Nagasaki City from 1961 through 1987. Subsequently, these cases of skin cancer in Nagasaki atomic bomb survivors were statistically analyzed in relation to the estimated distance from the hypocenter by age, sex, histology and latent period. The results were as follows: 1. A high correlation was observed between the incidence of skin cancer and the distance from the hypocenter. 2. The incidence of skin cancer in Nagasaki atomic bomb survivors now appears to be increasing in relation to exposure distance. 3. Among 140 cases, basal cell epithelioma was observed in 67 cases (47.9%) and squamous cell carcinoma in 43 cases (30.7%). PMID- 2246755 TI - Society for the Study of Fertility. Winter meeting, 1990. London, 17th-18th December. Abstracts. PMID- 2246754 TI - SCID (severe combined immunodeficiency) mice as a new system to investigate metastasis of human tumors. AB - In severe combined immunodeficiency (scid) mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) grew rapidly to enormous sizes in all of the animals after both subcutaneous and intraperitoneal transplantation, while only half of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice. Furthermore, transplanted tumors metastasized spontaneously to distant organs such as lung, liver, kidney, pancreas, and spleen in scid mice, while metastases were not found in athymic nude mice. Similar results were observed in scid mice and scid-nude (streaker) double mutant mice with human classic (typical) seminoma which has been neither transplantable nor metastatic in athymic nude mice. Thus, scid mice provide an invaluable experimental system to investigate the mechanism of metastasis which is the most important and life-threatening problem in cancer patients. PMID- 2246756 TI - Tommy N. Evans, M.D. A festschrift. PMID- 2246757 TI - Vaginal removal of the pedunculated submucous myoma. Historical observations and development of a new procedure. AB - A new method of vaginal removal of submucous fibroids was attempted on 151 patients. The procedure involves dilation of the cervix with Laminaria tents and removal of the submucous fibroid by grasping with appropriate instruments. Myomas were removed successfully in 92% of the patients; hysterectomy and abdominal myomectomy were avoided in all but four of them. Perforation occurred in two patients. Morbidity was minimal. The four patients who desired pregnancy conceived. PMID- 2246758 TI - A glance at the urodynamic database. AB - Three hundred sixty-four patients with urinary incontinence as their presenting complaint were evaluated in the urogynecology laboratory, Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York. Of them, 226 (62%) were found to have genuine stress urinary incontinence (GSI). This subset of demonstrably incontinent patients was characterized as to symptoms of stress and urge incontinence, incidence of nulliparity, occurrence of incontinence during intercourse and influence of weight on bladder pressure. Using clusters of symptoms did not accurately distinguish GSI from the other types of urinary incontinence. Four percent of the GSI patients were nulliparous. All had a reasonable explanation for incontinence other than anatomic relaxation. Twenty-three percent of the 154 sexually active GSI patients acknowledged having incontinence with intercourse. None of the anatomic and urodynamic parameters evaluated distinguished that group from their GSI counterparts who did not lose urine with intercourse. Increasing weight, expressed as the body mass index, correlated with an increase in the vesical pressure in the supine and standing positions. PMID- 2246759 TI - Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison. AB - Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed. PMID- 2246760 TI - Chorionic villus sampling as the primary diagnostic tool in prenatal diagnosis. Should it replace genetic amniocentesis? AB - Recent studies in Canada and the United States have shown that chorionic villus sampling (CVS) is both safe and accurate, with a fetal loss rate likely slightly higher than that of amniocentesis but still at an acceptable level (1%). Although CVS may become the dominant prenatal diagnosis procedure, it is unlikely that it will completely replace amniocentesis. The two procedures are essentially complementary in the provision of prenatal diagnosis in the first and second trimesters. PMID- 2246761 TI - Laser therapy for vaginal intraepithelial neoplasia after hysterectomy. AB - In recent years there has been a marked increase in the number of reported cases of vaginal intraepithelial neoplasia (VAIN) after hysterectomy. Until about 10 years ago radiation or surgery had been the therapeutic modality mostly used for this disease. More recently, topical drugs, such as bleomycin and 5-fluorouracil cream, have been used, but they are often ineffective and poorly tolerated. For the last 14 years we have used the CO2 laser for the treatment of VAIN and have treated a total of 143 patients. Our use of a combination of wire sutures through the vaginal mucosa and the introduction of fluids into the underlying submucosal areas allows retraction and ballooning of the recesses and scars and permits us to place the vaginal mucosa at right angles to the laser beam to allow complete treatment. PMID- 2246762 TI - Obesity and vaginal hysterectomy. AB - A retrospective study was done of 471 consecutive vaginal hysterectomies done in a three-year period. Three groups of patients--239 normal to 9% overweight, 132 10-24% overweight and 100 greater than or equal to 25% overweight--were compared. Surgical difficulties were similar in all three groups. The more obese patient had a slightly greater incidence of febrile morbidity, stayed one day longer in the hospital and had a minimally greater loss of hemoglobin 48 hours postoperatively. However, obesity per se caused few problems during and after vaginal hysterectomy. The vaginal approach is the procedure of choice for hysterectomy in obese women. PMID- 2246763 TI - The cytobrush for evaluating routine cervicovaginal-endocervical smears. AB - While the conventional wooden spatula/cotton-tipped applicator has remained the method of obtaining Papanicolaou smears for most clinicians at the University of California at Los Angeles, the Student Health Service (SHS) adopted the Zelsmyr cytobrush as its sole method of obtaining cervical samples in late 1986. A study was done to define changes in both the adequacy of sampling and the detection rate for both squamous and glandular epithelial abnormalities with the cytobrush. To accomplish this goal, 1,000 cytobrush and 244 conventionally obtained smears were analyzed prospectively, and 3,864 SHS samples obtained in 1986 prior to the change in method were reviewed retrospectively. As compared to cervical samples obtained by conventional methods, the cytobrush smears contained significantly more endocervical cells and had fewer drying artifacts. Both methods obtained equivalent squamous samples and had similar final class distributions. No case of endocervical adenocarcinoma carcinoma in situ or invasive adenocarcinoma was detected. SHS patients who had initial "no endocervical cells" samples but whose repeat sample did contain endocervical cells retained the same class in more than 75% of cases. This study confirmed that the cytobrush technique produces Papanicolaou smears with improved sampling of the squamocolumnar junction but questioned whether that results in an increased detection rate for cervical pathology. PMID- 2246764 TI - Initiating a chorionic villus sampling program. Relying on placental location as the primary determinant of the sampling route. AB - In initiating a chorionic villus sampling (CVS) protocol, we relied upon placental locations as the determinant in the choice of technique. An anterior or fundal location prompted a transabdominal (TA) CVS, while the transcervical (TC) approach was reserved for posterior placentas. A coaxial needle system was used for TA CVS (18-gauge, 15-cm guide needle and 20-gauge, 20-cm sampling needle), while TC CVS was accomplished with a 5.8-French, 27-cm polyethylene catheter. Between July 1988 and February 1989 our initial 118 procedures were performed for 115 consecutive pregnancies using this protocol. Testing indications and antenatal characteristics of the TA (n = 56) and TC (n = 63) groups were similar. One procedure failure occurred in the TC group, and a single aspiration was sufficient in 59% of the cases (TA, 30/55; TC, 39/63). In TC procedures an increased aggregate sample weight was observed as compared to TA cases (25.8 g vs. 16.9 g, respectively; P less than .001). This difference was not attributable to an increased number of placental aspirations in TC cases. One abnormal karyotype was observed (45X), and four pregnancy losses occurred (TC, 3; TA, 1). Using placental location to determine the choice of CVS technique appears to be feasible and may be associated with a lower failure rate during a facility's initial experience (when compared to reliance upon one technique alone). Trials comparing the safety of these two methods should consider placental location an independent variable before randomization. PMID- 2246765 TI - Hip pain in late pregnancy. AB - Hip pain in late pregnancy is quite common, and its etiology is rarely established unless acute demineralization occurs. We measured the bone mineral content of both hips in 26 women within 48 hours of delivery. Twelve of 36 densities (33%) were decreased in a group with severe pain when compared to 12 of 120 decreased densities (10%) in the remaining patients (P less than .05). Those data suggest that severe hip pain may be related to a decrease in bone mineral content. PMID- 2246766 TI - Aggressive evaluation for atypical squamous cells in Papanicolaou smears. AB - A retrospective study was done on women who had atypical Papanicolaou smears and were referred for immediate colposcopy. The smears were obtained during January 1985 to March 1989 at Edwards Air Force Base, California. Excluded from the evaluation were abnormal Papanicolaou smears with hyperkeratosis, parakeratosis and koilocytotic atypia suggestive of human papillomavirus (HPV) infection. The evaluation included colposcopy, colposcopically directed biopsies, endocervical curettage and repeat Papanicolaou smears. A total of 101 patients were included in the study. Cervical intraepithelial neoplasia (CIN) was seen in 29.7% (30 patients): 12.9% (13) CIN I, 12.9% (13) CIN II and 3.9% (4) CIN III. Carcinoma was seen in 3.9% (4) of the patients: 2.9% (3) was carcinoma in situ, and 0.99% (1) was invasive squamous cell carcinoma, stage IIb. HPV and dysplastic lesions were seen together in 19.8% (20) of the patients. HPV was seen alone in 45% (46). Twenty-one patients (20.8%) had no apparent lesions on colposcopy, although one developed microinvasive keratinizing squamous cell carcinoma within 36 months of colposcopy. Many significant lesions can go undetected for extended periods of time in women with atypical Papanicolaou smears, resulting in delayed management. Referral for immediate colposcopy is advocated strongly. PMID- 2246768 TI - Intrapartum cocaine use. A case report. AB - The use of cocaine during pregnancy appears to be reaching epidemic proportions. In the first reported case of intrapartum cocaine use, fetal heart rate abnormalities were detected. PMID- 2246767 TI - Vaginitis emphysematosa. A report of four cases. AB - It has been hypothesized that vaginitis emphysematosa is a manifestation of trichomonal or Gardnerella infection. In support of this etiologic concept, four cases of the disorder are described showing the apparent curative effect of treating the associated infection. The linkage of these and other reported cases with conditions of impaired immunity suggests that immunologic factors are involved in the pathogenesis. PMID- 2246769 TI - Report of the MRC Working Party on children conceived by in vitro fertilisation. PMID- 2246771 TI - Fragile Xq27.3 in female heterozygotes for the Martin-Bell syndrome. AB - X inactivation studies have been carried out on lymphocytes from eight unrelated females heterozygous for the Martin-Bell syndrome. Four of these carriers were of normal IQ and four were mentally handicapped. When BrdU was used to differentiate between the active and inactive X chromosome an average of 55% of fra(X) were active in the retarded subjects, but only 27% were active in those of normal IQ. When 3H thymidine was used to differentiate between the active and inactive X chromosome, an average of 58% of mitoses from handicapped subjects and 33% of mitoses from normal subjects showed an active fra(X) in informative cells. These results are compared with previously published studies and it is concluded that the number of inactive fra(X) chromosomes calculated as a proportion of all cells scored is the same in mentally normal and mentally retarded subjects. However, the number of active fra(X) chromosomes is consistently higher in the retarded than in the normal females. PMID- 2246770 TI - Mouse and hamster mutants as models for Waardenburg syndromes in humans. AB - Four different Waardenburg syndromes have been defined based upon observed phenotypes. These syndromes are responsible for approximately 2% of subjects with profound congenital hearing loss. At present, Waardenburg syndromes have not been mapped to particular human chromosomes. One or more of the mouse mutant alleles, Ph (patch), s (piebald), Sp (splotch), and Mior (microphthalmia-Oak Ridge) and the hamster mutation Wh (anophthalmic white) may be homologous to mutations causing Waardenburg syndromes. In heterozygotes, phenotypic effects of these four mouse mutations and the hamster mutation are similar to the phenotypes produced by different Waardenburg syndrome mutations. The chromosomal locations and syntenic relationships associated with three of the four mouse mutant genes have been used to predict human chromosomal locations for Waardenburg syndromes: (1) on chromosome 2q near FN1 (fibronectin 1), (2) on chromosome 3p near the proto oncogene RAF1 or 3q near RHO (rhodopsin), and (3) on chromosome 4p near the proto oncogene KIT. Waardenburg syndromes show extensive intrafamilial phenotypic variability. Results of our studies with the hamster mutation Wh suggest that this variability may be explained in part by modifier genes segregating within families. PMID- 2246772 TI - The Nance-Horan syndrome. PMID- 2246773 TI - Acquired alopecia, mental retardation, short stature, microcephaly, and optic atrophy. AB - We report on a female patient who had acquired total alopecia, short stature, microcephaly, optic atrophy, severe myopia, and mental retardation. A survey of published reports failed to show an identical patient, despite various similar cases. PMID- 2246774 TI - A de novo interstitial deletion of 15(q21.2q22.1) in a moderately retarded adult male. AB - An adult male is described with a de novo deletion 15q21.2-q22.1. He shares some minor dysmorphic features with similar cases but the degree of mental retardation is markedly less severe. PMID- 2246775 TI - Monozygotic twins with trisomy 18: a report of discordant phenotype. AB - The predicted incidence of liveborn monozygotic trisomy 18 twins is one per million births. The first case of liveborn monozygotic trisomy 18 twins was reported in 1989 and we report a second case in which striking phenotypic discordance existed. The probability of monozygotic trisomy 18 twinning and the mechanisms for phenotypic discordance in trisomic twins is discussed. PMID- 2246776 TI - Leiomyosarcoma in a patient with trisomy 8 mosaicism. PMID- 2246777 TI - Changes in electrical impedance of the vaginal medium during the menstrual cycle of female rhesus monkeys (Macaca mulatta). AB - Changes in electrical impedance of the vaginal medium during the menstrual cycle were recorded in female Rhesus monkeys using electrical probe and were correlated with estradiol-17 beta and progesterone plasma concentrations. A gradual decrease in impedance was observed during the follicular phase, the lowest values being observed between days 12-17 of the cycle. Impedance increased again during the first third of the luteal phase until day 21. The reversal of the impedance gradient's sign was nearly concomitant with the appearance of a detectable plasma progesterone concentration. These results support the use of vaginal impedance measurements as a help for the diagnosis of the periovulatory time in the female Rhesus monkey. PMID- 2246778 TI - Five months of daily standardized exercise for sedentary monkeys. AB - A system to physically exercise rhesus monkeys is described, based on their natural capacity to climb. It is composed of an enclosure where a motor-driven rope is continually going down. The two stage training to this task is easily performed. The total work of each run, evaluated with the weight of the animal and the distance climbed, may be very stable. It was used to provide five sedentary monkeys with daily physical training for five months. PMID- 2246779 TI - Horseshoe kidneys in vervet monkeys. AB - Two cases of horseshoe kidneys in vervet monkeys are described. Apart from the fusion, the rest of the urogenital system was anatomically normal and renal function was apparently not affected by this condition. The microanatomy was normal in both cases. PMID- 2246781 TI - Couples coping with chronic illness: women with rheumatoid arthritis and their healthy husbands. AB - Effects of a chronic disease, rheumatoid arthritis, upon the psychological adjustment of 103 women and their healthy husbands were examined. Husbands completed scales assessing perceived vulnerability to illness and coping efficacy, burden of caring for their wives, and level of psychological adjustment. Wives completed the Ways of Coping scale, rated attributions about arthritis, and rated criticalness and supportiveness of their husbands. Husbands were also interviewed and their responses coded for critical remarks about the wife. The same variables were used to predict each partner's adjustment in order to compare factors associated with each. Hierarchical regression indicated that negative marital interaction surrounding the wife's illness was a determinant of both partners' psychological adjustment. Apart from this variable, different factors predicted husbands' and wives' mental health. Husbands were most affected by their own perceived vulnerability to disease and coping inefficacy. Wives were most affected by pain severity and how they coped with arthritis. PMID- 2246780 TI - Cortisol response of female rhesus monkeys to venipuncture in homecage versus venipuncture in restraint apparatus. AB - Cortisol response of ten single-caged adult female rhesus monkeys during venipuncture in a restraint apparatus was compared with cortisol response of ten paired and five single-caged adult female rhesus monkeys during venipuncture in the homecage. Results demonstrated that in-homecage venipuncture offers a methodological improvement for research protocols that require blood collection of undisturbed animals. PMID- 2246782 TI - Coping with threats to health: effects of persuasive appeals on depressed, normal, and antisocial personalities. AB - Why do people frequently persist with unhealthy life-styles when they know they are harming themselves? To investigate the role of several personality variables, 114 depressed, antisocial, and normal individuals read health promotion and disease prevention communications about alcohol abuse, lack of exercise, and sexually transmitted diseases (STDs). The results revealed that, compared to a low-coping ability information condition, a high-coping ability condition motivated normal individuals to protect themselves but did not motivate either depressed or antisocial individuals. Additional findings indicated that threat appeals worked only if people were persuaded that they could cope with the health threats; attempts to frighten people without reassuring them had a deleterious effect. Men were more concerned than women about the costs of drinking in moderation, exercising, and protection against STDs and were more reluctant than women to give up the pleasures associated with heavy drinking and unprotected sex. PMID- 2246783 TI - Determinants of breast self-examination among women of lower income and lower education. AB - This study investigated breast self-examination (BSE) frequency and quality and determinants of BSE practice in two samples of women: (a) women of childbearing age who were of lower income and lower education and (b) women of childbearing age who were of higher income and higher education. Mothers recruited from a pediatric practice completed a questionnaire addressing BSE frequency and quality and factors derived from the Health Belief Model that might influence performance. Results indicated that there were no differences in mean BSE frequency or quality between the two samples. Regression analyses revealed that the perceived barriers index, consisting of forgetting, exclusive reliance on medical personnel for breast exams, and low confidence in ability to perform BSE, was the single best predictor of BSE frequency, accounting for 67% of the variance in each sample of women. When quality of BSE was examined, knowledge of BSE was the best predictor. PMID- 2246784 TI - Behaviors, beliefs, and intentions in skin cancer prevention. AB - This study investigated knowledge, behaviors, and health beliefs of Australian university students (n = 312) regarding skin cancers and evaluated the effects of videotaped presentations. Students' knowledge and health beliefs were assessed, and they then viewed either an informational video, an emotionally involving video, or a control video. Knowledge and beliefs were assessed immediately and 10 weeks later. Postvideo skin protection intentions increased significantly from prevideo assessment among the two intervention groups compared to the controls. Maintenance of skin protection intentions was higher with the emotional video. Health belief variables, particularly perceived barriers, were significant predictors of knowledge, intention, and behavior. However, other variables such as skin type and previous experience with skin cancer were more important. Females had greater knowledge and stronger intentions to prevent skin cancer than males but reported fewer high-risk behaviors. PMID- 2246785 TI - Magnetic resonance imaging scanning procedures: development of phobic response during scan and at one-month follow-up. AB - Between 5 and 10% of patients attempting a magnetic resonance imaging (MRI) scan become claustrophobic during the procedure. There has been a paucity of reported research in this area. This study was designed to investigate MRI-related phobia and identify risk factors for claustrophobia development. There were 108 subjects who had never had a scan, 57 males and 51 females, ranging in age from 19 to 72 years (mean age of 43 years). Subjects were evaluated before and after the scan and contacted for 1-month follow-up. Major findings included the following: (1) prescan report of pain was significantly correlated with stopping the scan, (2) prescan Fear Survey Schedule scores correlated significantly with reported claustrophic feelings after the scan, and (3) stopping the scan correlated significantly with follow-up report of an increase in claustrophobic feelings. Conclusions were that prescan pain and fear assessment may help predict, and allow intervention in, phobic response during and after the MRI scan. Implications for referring physicians and MRI technicians are discussed. PMID- 2246786 TI - Employee and organizational factors associated with participation in an incentive based worksite smoking cessation program. AB - This study investigated employee and worksite characteristics prospectively predictive of participation among 474 smokers in nine different worksites taking part in a year-long incentive-based smoking cessation program. Several different ways of defining participation (e.g., joining versus level of attendance, first 6 months versus entire program) were studied. A consistent pattern of results was observed across two of the participation indices, joining the program and participating in one or more monthly follow-up meetings. Both worksite (number of employees, previous health promotion history, degree of support from management) and employee (gender, motivation, previous quit attempts) variables were predictive of participation. Logistic regression analyses revealed that each set of variables, worksite and employee characteristics, was significantly related to participation after controlling for the effects of the other set. We were less able to predict level of attendance among participants who joined the program. Implications of these findings for future studies of participation in health promotion programs are discussed. PMID- 2246787 TI - Marital relationships and Type A-B behavior assessed using the structured interview, Jenkins Activity Survey, and Framingham Type A Scale. AB - Associations between spouses' Type A/Type B Behavior and marital distress, communication, and desired relationship changes were investigated in a sample of 42 healthy Caucasian couples aged 39 to 60 years. Consistency of relationships between marital distress and behavior type (BT) across different BT measurement techniques was also evaluated. BT was measured using the Structured Interview (SI), the Jenkins Activity Survey (JAS), and the Framingham Type A Scale (FTAS). Type A behavior in women was associated with increased marital distress and communication difficulties, as reported by both men and women. Participants also desired greater relationship changes when women were Type A. Findings varied greatly across BT measures. The strongest effect occurred for the FTAS, followed by the JAS. No significant effects were found for SI-assessed BT. Results reflect the multifaceted nature of the Type A construct and may reflect gender role differences within marital relationships. PMID- 2246788 TI - Effects of growth on architecture and functional characteristics of adult rat gastrocnemius muscle. AB - Changes of architecture of adult rat gastrocnemius medialis muscle (GM) due to growth were studied in relation to length-force characteristics. Myofilament lengths were unchanged, indicating constant sarcomere length-force characteristics. Number of sarcomeres within fibers was unchanged as a consequence of growth, allowing persistence of differences between proximal and distal fibers in all age groups. Distal fiber length at muscle optimum length was shorter for the 14- than for the 10- and 16-week age groups despite a lack of difference of number of sarcomeres. This is indicative of a shift of optimum length. Some evidence for the occurrence of distribution of fiber optimum lengths with respect to muscle optimum length was found in other age groups as well, albeit of a smaller magnitude. Muscle and aponeurosis length increased substantially with growth. Functional effects of increased aponeurosis lengths were increased contributions to muscle length changes by the aponeurosis, allowing smaller fiber contributions in older animals. Fiber angle increased approximately 5 degrees with growth. Despite the differences of architecture indicated above, muscle length range between optimum length and active slack length was constant. This was probably caused by widening of this length range in the youngest age group by variations of architecture within the muscle. It is concluded that adaptation of aspects of muscle architecture is an important mechanism for adult muscle growth in rat GM. Of these aspects regulation of muscle length seems a dominant factor. PMID- 2246789 TI - Paralysis and growth of the musculoskeletal system in the embryonic chick. AB - Avian embryos can be completely paralyzed by injection of neuromuscular-blocking agents. We used a single injection of decamethonium iodide to paralyze embryos at 7, 8, or 10 days of incubation and analyzed the growth of individual bones (clavicle, mandible, ulna, femur, tibia, humerus) and of individual muscles that act upon some of those bones (clavicular and sternal heads of m. pectoralis, and mm. biceps brachii, depressor mandibulae, pseudotemporalis, and adductor externus). Growth of the bones is not equally affected by paralysis. Only 27% of clavicular growth (by mass) but 77% of mandibular growth occurred in paralyzed embryos, whereas the four long bones exhibited 52-63% of their normal growth. Analysis of muscle weight, fiber length and physiological cross-sectional area (weight/fiber length) indicate that there was greater reduction of the muscles acting on the limbs than of those acting on the mandible, i.e., diminished growth of the skeleton is correlated with reduced muscular activity. Specific retardation of clavicular growth is due to fusion of sternal rudiments and collapse of the thorax, as well as virtual absence of the musculature that normally attaches to the clavicle. We discuss these results in the light of intrinsic and extrinsic factors governing growth of the embryonic skeleton. Paralysis reduces skeletal growth by reducing both the movements taking place in ovo, and the loads imposed on the bones by muscle contraction, changes that represent alterations in the mechanical environment of the skeleton. PMID- 2246791 TI - Treating sexual dysfunction associated with prior sexual trauma. AB - Negative, confusing, guilt-inducing, or traumatic sexual experiences are almost universal for both females and males. Guidelines are presented for assessing sexual trauma using the medium of the detailed sexual history. The cognitive behavioral treatment strategy considers past trauma in the context of the present sexual dysfunction rather than an issue to be dealt with first or separately. The guiding principles are to teach the person to be a "survivor" rather than a "victim" and to help the couple develop a functional and satisfying sexual style because "living well is the best revenge." PMID- 2246790 TI - Educational intervention as an adjunct to treatment of erectile dysfunction in older couples. AB - This study examined the effects of a sex and aging workshop highlighting permission and limited information on the sexual knowledge, attitudes, behaviors, and satisfaction of a group of older heterosexual couples experiencing erectile dysfunction. The workshop focused on disseminating information about the physiological and psychological changes that occur in the sexual response during the aging process. Twenty couples participated in this study: 10 attended a workshop and 10 served as controls. The study utilized a randomized control group pretest/posttest design. Workshop participants completed an evaluation form and were interviewed at the time of follow-up. Data analysis revealed that the workshop participants reported significant increases in knowledge levels and in sexual satisfaction. The workshop evaluations and follow-up interviews reinforced these quantitative results. This study lends support to educational intervention as an adjunct to treatment of erectile dysfunction in the elderly population. PMID- 2246793 TI - Play therapy with the sexual workhorse: successful treatment with twelve cases of inhibited ejaculation. AB - This paper explores play as treatment for inhibited ejaculation (IE), based on success with 12 heterosexual and homosexual men. The focus is on men able to ejaculate with their own touch but not with partner touch or penile containment. A definition of IE includes: compulsive need to please partner, response anxiety, nonsexual automatic erections, and the penis's refusal to be commanded interpersonally. Treatment options with individuals and/or couples begin with reframing the symptom as compulsive giving and are not directed at forcing ejaculation. Playing, interfering with erroneous beliefs about sexual arousal, and avoiding helping the workhorse work harder are the trust of this paper. PMID- 2246792 TI - Involuntary childlessness and marital adjustment: his and hers. AB - This study of 103 couples in treatment for infertility suggests that spouses are generally similar in the way they perceive their marital adjustment, but that they arrive at their views by different routes. Acceptance of a childless lifestyle is consistently associated with greater marital adjustment for men, but greater stress associated with infertility undermines marital adjustment for both husbands and wives. Men adjust better to an involuntarily childless marriage if their wives are employed or have high earnings. Wife's marital adjustment diminishes with the length of the marriage and the course of treatment for infertility. The stress women experience as a result of infertility influences their perception of their marriage and may undermine their ability to get the support they need during the transition to nonparenthood. PMID- 2246794 TI - A randomized clinical trial of cognitive marital therapy. AB - Thirty-three couples with severe marital discord referred to a psychiatric outpatient department were randomly assigned to Cognitive Marital Therapy or a control group. Cognitive Marital Therapy is a brief, structured couple therapy, which involves spouses in reciprocal self-disclosure of personal constructs. The control group received the same number of sessions of self-disclosure from a programmed marital enhancement text. Personal distress, marital adjustment, marital quality, and aspects of self-disclosure were measured before and after treatment. Symptoms of depression as well as somatic and compulsive complaints showed significant improvement in both groups. The wives exhibited a trend suggesting that they were making more self-disclosures to their spouses after counseling. No discernable differences in outcome were found between the marital therapy group and the control group. Marital intimacy and marital satisfaction did not improve significantly over the course of 10 therapy sessions. This study suggests that the role of self-disclosure in marital therapy needs further clarification. PMID- 2246796 TI - Proceedings of the 54th annual scientific meeting of the Japanese Circulation Society. March 1990, Fukuoka. Abstracts. PMID- 2246795 TI - The use of PotenTest in the multidisciplinary evaluation of impotence: is it a reliable measure? Jefferson Sexual Function Center. AB - This study compares the findings of multidisciplinary evaluation to the three night use of the PotenTest, a standardized stamp test for the evaluation of nocturnal penile tumescence, in 174 patients. An organic etiology was diagnosed in 54% of those evaluated. The PotenTest proved accurate as a screening device for organic disease. Among the 48 patients who did not break any of the stamps over the three nights, 40 were found to have an organic basis for their erectile failure, for a predictive value of 83%. Among the 68 patients who broke all of the stamps, 45 were found to have a psychogenic basis for their erectile failure, for a 66% predictive value. When one or two of the stamps were broken over the three nights, the predictive values as to the etiology of the erectile failure were considerably diminished and of no diagnostic value. Results for only one night of usage revealed that of the 73 patients who did not break the stamps, 56 (77%) were found to have an organic etiology. Of the 101 patients who broke the stamps on the first night, 63 (62%) were found to have a psychogenic etiology. PMID- 2246797 TI - [Anesthesiologists in current medical practice in Japan]. PMID- 2246798 TI - [A benzodiazepine antagonist flumazenil in clinical use--a dose finding study]. AB - The effective dose, usefulness and side effects of flumazenil, a specific benzodiazepine antagonist, have been investigated in 72 sleeping patients after the end of the surgical operation who had received flunitrazepam 0.03 mg.kg-1, a long acting benzodiazepine. The patients received intravenous injections of flumazenil 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg per person as initial doses. Four minutes after the injection of flumazenil, the percentages of the patients who were awake, were 47.4% in 0.1 mg group, 82.4% in 0.2 mg group, 82.4% in 0.4 mg group and 88.2% in 0.8 mg group respectively. There were several side effects observed in all the groups except 0.2 mg group. However, they presented no clinical problems. Therefore, flumazenil 0.2 mg as the initial dose, is considered appropriate. PMID- 2246799 TI - [Antagonism of diazepam-induced sedative effects by flumazenil in patients after surgery under lumbar spinal or epidural anesthesia]. AB - The efficacy and general safety of flumazenil (YM684), a specific benzodiazepine antagonist, have been evaluated. Forty-seven patients scheduled for surgery under lumbar spinal or epidural anesthesia with diazepam sedation received flumazenil at the end of the procedure. Criteria of efficacy were the degree of sedation and antegrade amnesia. Before injection all patients were heavily sedated with the mean dose of 27 mg of diazepam (range 10-50 mg). After the mean dose of 0.21 mg of flumazenil (range 0.2-0.4 mg), all patients were awake or drowsy within 1-6 min but sedation recurred in one patient 1 hour later. The amnesia was eliminated by flumazenil in 34 patients (72%). No serious side-effects or hemodynamic changes were observed after flumazenil. It is concluded that flumazenil is an effective antagonist of sedation induced by diazepam. PMID- 2246800 TI - [EEG analysis of the effectiveness of the benzodiazepine antagonist RO 15-1788 after diazepam sedation]. AB - In ten volunteers given diazepam, a new diazepam antagonist RO 15-1788 was administered and the effectiveness of this drug was analyzed on EEG. EEG electrodes were attached at C3 and C4 taking right and left ear lobes as indifferent electrodes. EEG trend monitor used by us was equipped with a Fourier analyzer as well as a conventional EEG recorder. EEG was recorded first for about 15 minutes at rest with eyes closed, followed by intravenous injection of 10 mg diazepam. At the end of the test, the antagonist, RO 15-1788 0.5-0.8 mg was administered. Slow waves and alpha waves were frequently found at rest with eyes closed. After diazepam administration, however, power spectrum percent in rapid waves (13-17.5 Hz) mainly consisting of beta waves increased from 8.0 +/- 1.3% (mean +/- SE) to 19.9 +/- 2.2%. These changes were statistically significant (P less than 0.05). At the end of procedures RO 15-1788 was administered and percent of power spectrum in beta waves decreased from 17.4 +/- 2.8% to 9.5 +/- 1.5%. These changes were also statistically significant (P less than 0.05). The sedative effect of diazepam may be evaluated by monitoring these rapid waves since the antagonizing effect of RO 15-1788 is demonstrated on EEG. PMID- 2246801 TI - [Total intravenous anesthesia with continuous infusion of midazolam]. AB - Continuous infusion of midazolam and fentanyl were used in total intravenous anesthesia. Anesthesia was induced with midazolam 0.3 mg.kg-1 in 100% O2. Tracheal intubation was facilitated with succinylcholine 1 mg.kg-1 after precurarization with pancuronium 1 mg. The infusion regimen of midazolam was as follows; an initial infusion of 0.68 mg.kg-1.hr-1 for 15 min followed by a maintenance infusion of 0.125 mg.kg-1.hr-1, and about 30 min before the end of operation infusion was stopped. Fentanyl and pancuronium were injected as required. During operation, blood pressure and heart rate were stable with a small dose of nicardipine. Total dose of fentanyl was the same as in NLA. Extubation was done as quickly as in NLA, after aminophylline infusion which was said to reverse midazolam. In the recovery room, patients were asleep and snored. But they opened eyes and responded to verbal command. Respiratory rate and PaCO2 were in normal ranges. Total intravenous anesthesia was possible with midazolam and fentanyl but a further study is necessary. PMID- 2246802 TI - [Intraoperative ischemic change demonstrated on lead V5 related to hemodynamic episodes as well as sites and degree of coronary vascular lesion]. AB - Electrocardiographic (ECG) changes demonstrated on lead V5 were investigated regarding the effect of hemodynamic change as well as site and degree of the LAD stenosis. Results were summarized as follows. 1. Myocardial ischemic changes on lead V5 occurred in the patients with two or more stenosis on LAD when heart rate increased. 2. Total occlusion of LAD with collaterals from stenosed RCA showed ischemic change on hypotension due to partial perfusion of cardiopulmonary bypass. 3. Ischemic changes occurred in patients with spontaneous angina and non transmural myocardial infarction when the pericardium was opened. 4. Induction of anesthesia with fentanyl and droperidol kept blood pressure lower, but with this method no ischemic change on lead V5 occurred before CPB. PMID- 2246803 TI - [Intraoperative cardiac output monitoring by the transtracheal Doppler method]. AB - We investigated the cardiac output measured with a transtracheal doppler (TTD) tube in surgical patients and evaluated its usefulness during operations. This tube was located at the point where maximum velocity of blood flow was obtained in the ascending aorta. At this point the cross-sectional area of the ascending aorta was calculated and the cardiac output was obtained by multiplying this area with average blood flow velocity which had been ultrasonically determined. The cardiac output by the TTD method was compared with that of the thermodilution method in 10 patients. The results with both groups showed a direct linear correlation. We obtained the following linear equation: TTD C.O. = 0.61 Thermo C.O. + 1.3 C.O.: cardiac output. The direct correlation coefficient proved to be 0.85 at a risk factor of 0.01. The result suggests that this non-invasive TTD method is easily available and useful in monitoring the intraoperative cardiac output. PMID- 2246804 TI - [The effectiveness of angiotensin II antagonist on experimental pulmonary embolism--comparison of propranolol with prostaglandin F2 alpha]. AB - We studied the effects of angiotensin II (A-II) antagonist, propranolol and prostaglandin F2 alpha (PGF2 alpha) on arterial hypoxemia after injecting autologous muscle to induce massive pulmonary embolism. Twenty-four anesthetized paralyzed dogs were divided into four groups; control, intravenous A-II antagonist (1-sarcosine, 8-isoleucine A-II) infusion at 5 micrograms.kg-1.min-1, intravenous propranolol injection at 1.5-2.0 mg, and intravenous PGF2 alpha infusion at 1 microgram.kg-1.min-1. With FIO2 of 0.33, the administration of A-II antagonist produced an increase in arterial PO2 from 134 +/- 16 (mean +/- SE) to 155 +/- 11 mmHg during infusion, and to 160 +/- 9 mmHg 30 min after infusion. Simultaneous hemodynamic measurements demonstrated no significant changes in arterial blood pressure and heart rate, but a slight increase in cardiac output was observed. On the other hand, propranolol and PGF2 alpha did not reverse the pulmonary oxygenation. Cardiac output decreased after propranolol, and alveolar dead space and pulmonary artery pressure increased further after PGF2 alpha. We conclude that A-II antagonist may be effective in the treatment of massive pulmonary embolism, possibly by improving the ventilation-perfusion relationship. The exact mechanism of the effect of A-II antagonist has not been clarified. PMID- 2246805 TI - [Perioperative renal function of patients with chronic renal diseases]. AB - Perioperative renal function was studied in the patients with compensated renal failure whose values of BUN and serum Cr were above 30 and 2mg.dl-1 respectively, and those with chronic renal diseases whose values of BUN and serum Cr were normal. Serum and urine electrolyte, urea N, beta 2 microglobulin, Cr, Ccr, FENa and urine N-acetyl-beta-D-glucosaminidase were checked before, during and after operation for 2 weeks. Anesthesia mainly chosen was neuroleptanesthesia with vecuronium. In both groups, the function of glomeruli was not influenced during perioperative period. In both groups, during operation and 5 to 8 days after operation the value of FENa increased and returned to the preoperative value on the 14th postoperative day. The value of urine beta 2 microglobulin increased on the 5th postoperative day in both groups. During perioperative period renal tubular function was mainly influenced and returned to preoperative value 5 to 14 days after the operation. The perioperative care of the patients with chronic renal diseases including compensated renal failure is different from that of the patients with renal failure treated by hemodialysis. PMID- 2246807 TI - [Changes in plasma superoxide dismutase like activity during general anesthesia and surgery in man]. AB - Superoxide radicals are highly reactive products that are known to induce various pathological changes in man. Superoxide dismutase is an enzyme that scavanges superoxide radicals. We measured plasma superoxide dismutase (SOD) like activity according to electron spin resonance using DMPO as a trap. The subjects of the study were 48 surgical patients who underwent various elective surgery. They ranged from 10 to 74 years in age. Anesthetic agents employed were enflurane in 50% O2 + 50% N2O, modified NLA with pentazocine, original NLA and fentanyl + ketamine (FK). In NLA group, 70% N2O and 30% O2 were given and 70% air and 30% O2 were administered to the patients of FK group. The mean plasma SOD like activity before the anesthetic induction in surgical patients of all groups was 5.70 +/- 0.41 U.ml-1. There is no significant difference compared with the value of normal persons. A marked reduction in plasma SOD like activity was obtained during surgery in any type of anesthesia in this study. Neither anesthetic agents used in this study nor the extent of surgery contributed to the degree of SOD like activity reduction. Surgical duration over two hours was the most contributing factor to reduce the SOD like activity. There was no correlation between plasma SOD like activity and age or serum total protein. PMID- 2246806 TI - [Effect of isoflurane and enflurane on ICG-clearance]. AB - We performed ICG-test (indo-cyanine green test) during surgery to study the effect of isoflurane and enflurane on ICG clearance in human. When the systolic arterial pressure (SAP) was maintained at 70% of the preoperative base line value, a significant decrease in ICG clearance occurred in the patients who received enflurane. Isoflurane, on the contrary, did not cause such a decrease in the ICG clearance. We conclude that isoflurane may restore either the blood flow to the liver or the liver function and the liver may remove ICG from the blood much better under isoflurane than under enflurane. PMID- 2246808 TI - [Effects of succinylcholine on serum levels of myoglobin and CK in children under halothane or enflurane anesthesia]. AB - We studied the effects of succinylcholine (SCC) on serum levels of myoglobin (Mb) and CK in children under halothane or enflurane anesthesia. Forty-five children, aged 2 years 11 months to 12 years 6 months were subjected to this study. They were divided into four groups; the two groups were injected with SCC 1 mg.kg-1 intravenously to facilitate tracheal intubation and maintained with halothane (Group SH) or with enflurane (Group SE). The other two groups were intubated without the aid of SCC and maintained with halothane (Group H), or with enflurane (Group E). Mb was analyzed by an antibody radioimmunoassay technique and CK was analyzed by a modified Rosalki's method. While Mb increased in all four groups, the increase was pronounced in the SCC groups (60 min value of Group SH 2192 +/- 639 ng.ml-1, Group SE 1722 +/- 436 ng.ml-1, mean +/- SE), and the increase was significantly smaller in SCC free groups (Group H 40 +/- 12 ng.ml-1, Group E 43 +/- 9 ng.ml-1). The CK value increased only in the SCC groups to 174.1 +/- 32.8 IU.l-1 in Group SH, and to 193.6 +/- 35.7 IU.l-1 in Group SE at 60 min, respectively. These results indicate that increases in Mb and CK values were mainly induced by SCC injection and that SCC might play some roles in development of malignant hyperthermia. PMID- 2246810 TI - [Acoustic evaluation of postoperative hoarseness in adult patients]. AB - The present study was performed to evaluate postoperative hoarseness quantitatively by means of acoustic wave form analysis. Pitch and amplitude perturbation (PPQ, and APQ), and normalized noise energy (NNE) were measured along with the frequency characteristics in 51 adult patients undergoing elective surgery. The normal values for these acoustic parameters were less than 0.5%, less than 2.0%, and less than -10 dB, respectively. Vowel sound "E" was recorded and evaluated before the induction of anesthesia and on the morning of the day after the surgery. PPQ increased from 0.39% to 1.00% (P less than 0.05), APQ increased from 3.34% to 6.62% (P less than 0.05), and NNE increased from -9.19 dB to -4.74 dB (P less than 0.05). Eighteen percent of the patients showed abnormal values in all parameters preoperatively, but 45% of the patients postoperatively (P less than 0.05). These findings suggest that even the short term intubation resulted in the postoperative hoarseness, and this method is a useful and non invasive bed-side test to evaluate postoperative hoarseness quantitatively. PMID- 2246809 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--1. Introduction]. AB - We have developed a new method of total intravenous anesthesia with droperidol, fentanyl and ketamine and have administered it to more than 400 surgical patients, ranging in ages from 4 to 80 years. Cardiac and neurosurgical patients were excluded. After establishing a routine monitoring, droperidol 0.06-0.1 ml.kg 1 was slowly given. After 5 minutes, fentanyl 1-2 micrograms.kg-1 and ketamine 1.0-1.5 mg.kg-1 were slowly administered intravenously. Trachea was intubated following intravenous succinylcholine. A total dose of 5-15 micrograms.kg-1 of fentanyl was given intravenously with a continuous infusion of ketamine 2 mg.kg 1.hr-1 during surgical procedure. Air and O2 (FIO2 0.30-0.35) were given and muscle relaxation was achieved with necessary dose of intravenous pancuronium or vecuronium and no inhaled anesthetic was given. Total intravenous anesthesia has many advantages such as no air pollution in the operating theatre, empty bowels, no organ (hepato-renal) toxicity, good peripheral perfusion and low cost, while this method has several disadvantages to overcome such as hypertension. There are many anesthetic agents for total intravenous anesthesia. However, sufentanil, alfentanil and propofol are not available. Droperidol, fentanyl and ketamine are the best combination for this purpose in Japan so far. PMID- 2246811 TI - [Perioperative hemodynamic changes and management of hemodialysed patients]. AB - Perioperative hemodynamic changes of hemodialysed patients were investigated and the changes of emergency cases (group E, n = 8) were compared with those of scheduled ones (group S, n = 13). By preoperative hemodialysis (HD), the values of blood urea nitrogen, serum creatinine, serum potassium, serum bicarbonate, and hematocrit were adjusted within normal range in group E, with no significant difference from those of group S. On the other hand, concerning the effect of preoperative removal of body water by HD, cardio-thoracic ratio (CTR, 53.6 +/- 3.1%) and pulmonary artery diastolic pressure (PADP, 11.6 +/- 5.0 mmHg) of group E were significantly higher than those of group S (CTR = 46.9 +/- 4.5%, PADP = 7.8 +/- 3.0 mmHg), indicating that the removal of body water by preoperative HD might be less in group E. However, group E patients required more administration of fluid and pressor agents in order to maintain their blood pressure and/or cardiac output during operation. Although with less water removal preoperatively and more fluid intraoperatively, postoperative PADP was significantly reduced (8.3 +/- 3.0 mmHg) in group E, suggesting that the requirement of perioperative water is more in group E. We conclude that the safe perioperative hemodynamic management for emergency surgery of hemodialysed patients requires following points; (1) The excessive removal of body water by preoperative HD should be avoided. (2) Intraoperative fluid infusion should be adequate so that they do not fall into hemodynamic collapse. PMID- 2246812 TI - [Usefulness of continuous SV(-)O2 monitoring during hepatectomy]. AB - The mixed venous oxygen saturation (SV(-)O2) was continuously monitored during hepatectomy including the resection and reconstruction of great vessels in five patients. During the artificial bypass, the inadequacy of venous return due to failed bypass and/or hemorrhage was detected by the monitoring of SV(-)O2. Low cardiac function and the effect of a vasodilator were also confirmed by this monitoring. The conventional monitoring, such as blood pressure and heart rate, did not always reflect the acute changes in patients' hemodynamics. The monitoring of SV(-)O2 is useful in the anesthetic management during the surgeries which are accompanied with acute hemodynamic changes. PMID- 2246813 TI - [Anesthetic management of a patient with a giant ovarian tumor complicated with cerebral palsy]. AB - The anesthetic management of a patient with a giant ovarian tumor (16.5kg) was reported. The patient was a 32 year old female with cerebral palsy and severe mental retardation. The management of anesthesia in this case including induction of anesthesia, intra-operative hypotension due to removal of tumor and post operative pulmonary complication, should be considered carefully. Especially, the monitoring of central venous pressure was essential, because the venous return fluctuates markedly depending on the surgical procedure. Patient had no premedication. Anesthesia was induced with halothane, nitrous oxide and oxygen by mask with the monitoring of ECG, and radial arterial as well as central venous pressure. Following easy tracheal intubation, bronchospasm occurred, which induced multifocal PVC's. This PVC turned to bigeminy and treatment with such drug as lidocaine was not effective. Anesthesia was maintained with enflurane, nitrous oxide and oxygen. Bigeminy disappeared 5 minutes after discontinuing enflurane anesthesia. Post-operative course was uneventful. The merit of slow induction method with halothane, nitrous oxide and oxygen has not been proved in this special case. PMID- 2246814 TI - [Relief of intractable post-herpetic neuralgia with gasserian ganglion block using methyl prednisolone acetate and with TENS]. AB - A 58 year old man had been suffering from intractable left ophthalmic post herpetic neuralgia (PHN) for 7 years. He has also been treated for polyarteritis nodosa for 10 years. For pain relief, he was treated initially with frequent (4 times a day) stellate ganglion block (SGB) and peripheral ophthalmic nerve block for a month without relief. Then supraorbital nerve block with neurolytics, TENS and acupuncture were done with a slight relief of his pain. Recently his pain became worse even with imipramine 75 mg and carbamazepine 100 mg a day which relieved effectively the patient from the pain for the last 3 years. The pain was so severe to disturb his usual daily activity. Gasserian ganglion block with methyl prednisolone acetate 10 mg was done. After the block, his ADL improved markedly. Three months after the block, he had no spontaneous pain and slight pain with light touch on the injured skin did not annoy him. Several days before the block, electric stimulation to control his pain was tested. Stimulation with the electricity (4.5 mA, 10 cycle and 400 microseconds) brought him complete relief from the pain during the stimulation. Trigeminal SEP showed no response to the stimulation of injured skin. PMID- 2246815 TI - [Evaluation of the safety of a new portable pump for continuous epidural infusion of local anesthetics]. AB - The safety of a new portable pump (Baxter Infusor), was evaluated for continuous epidural infusion of local anesthetics. The experimental flows at different temperatures were 1.87 ml.hr-1 at 28 degrees C and 2.14-2.15 ml.hr-1 at 33 degrees C. The average temperature of local anesthetics in this pump attached to patients was 29 degrees C. Concentration of mepivacaine reached the maximal value (1.129 +/- 0.439 micrograms.ml-1) at 12 hours after the application of the infusor. The concentration of mepivacaine was maintained at a constant level from 6th hour to 24th hour. The result indicates that Infusor is a safe device for continuous infusion of local anesthetics because of constant flow and low level of local anesthetics. PMID- 2246816 TI - [Role of PMN elastase in fibrinolytic activity in patients with acute promyelocytic leukemia]. AB - In order to define a specific acceleration of fibrinolytic activity in acute promyelocytic leukemia (APL), we determined fibrinolytic factors in APL and acute myeloblastic leukemia (AML). An increase in plasma levels of D-dimer was observed in both APL and AML, indicating that there is an acceleration of fibrinolysis in both types of leukemia. The levels of D-dimer/FDP ratio were significantly lower in APL than AML. These findings suggest that fibrinogenolytic activities were higher in APL that in AML. The relationship between the plasma levels of plasmin alpha 2PI complex (PIC) and FDP was investigated to study whether fibrinolysis was induced by plasmin. PIC levels were linearly correlated with FDP levels in AML, while in APL there was no close correlation between the plasma levels of PIC and FDP. Then, we measured PMN elastase-alpha 1 proteinase inhibitor complex (E alpha 1 PI). There was a correlation between the plasma levels of E-alpha 1PI and FDP in APL but not in AML. Furthermore, PMN elastase activity was detected in leukemic cell lysate in patients with APL but not in AML. These findings suggest that PMN elastase may be an important factor in the induction of fibrinolysis in APL. PMID- 2246817 TI - [Cyclosporin therapy for aplastic anemia]. AB - We treated 14 patients with aplastic anemia (6 severe, 8 moderate) who did not respond to high dose methylprednisolone, antilymphocyte globulin, or anabolic steroid with cyclosporin (CyA) for more than 4 weeks. Four of them (29%) showed clinical improvement to transfusion-independence. The response rate of patients who received CyA more than 5 weeks was 50% (4 out of 8). The dose of CyA given to the 4 patients who improved after the therapy was 5 to 9 mg/kg/day. One patient needed 11 weeks until the first sign of response (increase of reticulocytes) appeared. In the other three patients, platelets increased first in response to CyA within 5 weeks. Side effects such as hypertricosis and gingival hyperplasia were frequently seen during the CyA therapy, but since they were not so severe or transient, almost all patients tolerated the therapy. These results indicate that CyA can be an efficacious drug for patients with refractory aplastic anemia. Long term treatment with a relatively low dose of CyA may be important for obtaining a high response rate. PMID- 2246818 TI - [A family with von Willebrand disease and hypofibrinogenemia]. AB - A family with two complex disorders of hemostasis, von Willebrand disease (vWD) and hypofibrinogenemia was reported. The probands were 21- and 16-year-old full brothers suffering from serious bleeding tendencies from childhood. The elder brother had a subarachnoid hemorrhage at the age of 15. The younger brother had repeated episodes of gastrointestinal bleedings since he was 10 years of age. Coagulation studies revealed that both of them had almost the same hemostatic abnormalities, i.e. severe vWD, 9 to 12% of plasma vWF levels, and mild hypofibrinogenemia, 125 to 130 mg/dl of plasma fibrinogen levels. Multimeric compositions of their vWF were normal, and functional assay for fibrinogen concentration yielded essentially the same values as did immunologic assay. These results indicated that they had two complex disorders, extreme type I vWD and heterozygous state of afibrinogenemia resulting in serious bleeding tendency. Family study showed that these two hemostatic disorders were paternal inheritance, and it was strongly postulated that vWD and hypofibrinogenemia might be highly-combined hemostatic disorders. PMID- 2246819 TI - [Successful pregnancy outcome in a patient with HbE/beta (0)-thalassemia]. AB - Successful pregnancy outcome is described in a patient with hemoglobin E/beta(0) thalassemia which is expressed as thalassemia major. A 21 year-old Laotian female complicated by severe anemia became pregnant. The diagnosis of hemoglobin E/beta (0)-thalassemia was made by hemoglobin analysis. The fetal weight estimated by abdominal echogram decreased during pregnancy. She received blood transfusions, in order to improve intrauterine growth retardation. Hemoglobin concentration was maintained at the level greater than 9 g/dl. Fetal growth was improved by the treatment. A normal full-term male infant was born by a caesarean section, and splenectomy was performed at the same time. PMID- 2246820 TI - [Systemic mast cell disease associated with cutaneous xanthomas and markedly elevated serum IgE]. AB - Systemic mast cell disease (SMCD) is a rare disease often associated with symptoms of general malaise, pruritus, diarrhea, vomiting, fever, urticaria pigmentosa, hepatosplenomegaly and lymphadenopathy. We reported a case of SMCD associated with cutaneous xanthoma and serum hyper IgE. Skin biopsy revealed xanthomas and diffuse infiltration of mast cells in the dermis. The association of SMCD with xanthoma was reported in the literature for only one case. The hyper IgE could be due to the defect of IgE receptors on the cell membrane of mast cells of dysfunction of T and/or B cell. Any of the treatment using H1 and H2 receptor blockade, disodium cromoglycate, adrenocorticosteroid or chemotherapy (VEPA) were not effective. The patient died of pulmonary edema and multiple organ failure 7 months after the diagnosis was established. The crush method for the cytological examination of bone marrow was considered more useful than smear method for the diagnosis of SMCD. PMID- 2246821 TI - [Treatment of paroxysmal nocturnal hemoglobinuria with danazol]. AB - Glucocorticoid and androgen therapy have been used with moderate success in paroxysmal nocturnal hemoglobinuria (PNH). However, both are poorly tolerated, especially in women, although the side effects of glucocorticoid can be diminished by alternate day therapy. We have treated two patients with PNH with danazol. One of patient is man, 64 years old age with stomach cancer, and the other patient is 34-year-old man. Their disease has existed for 6-14 years. They required many blood transfusions, their hemoglobins ranging between 7.1 and 9.9 grams per deciliter. When treated with danazol by mouth, the hemoglobin level increased approximately 2 to 5 grams in each patient within 3 week, and clinical hemoglobinuria improved. None of the patients has had any side effects. PMID- 2246822 TI - [Acquired von Willebrand syndrome with autoimmune hemolytic anemia]. AB - Acquired von Willebrand syndrome is reported in a 31-year-old woman with autoimmune hemolytic anemia (AIHA). The patient, who had no family history of bleeding, presented with a hemorrhagic diathesis of recent origin. Routine coagulation studies showed a normal platelet count, prolonged bleeding time and abnormal glass bead retention. Plasma levels of factor VIII-von Willebrand factor (F VIII-vWF) were low and ristocetin-induced platelet aggregation (RIPA) was decreased. In vitro, the patient's plasma exhibited inhibitory activity against vWF: ristocetin cofactor activity (vWF: Rco) but had no effect on RIPA. The multimeric pattern of the patient's vWF resembled that of patients with inherited type II von Willebrand disease, in that the largest multimers were missing. Clinical improvement resulted after treatment of AIHA with prednisolone (PSL), and F VIII-vWF returned to normal levels with normalization of vWF multimers. However, following tapering the dose of PSL, plasma levels of F VIII-vWF again decreased. PMID- 2246823 TI - [Bone marrow transplantation for MDS]. AB - Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities. PMID- 2246824 TI - [Prominent lymphadenopathy and double Ph1 chromosomes as initial and recurrent manifestations of chronic myelogenous leukemia in blast crisis: report of a case and review of the literature]. AB - A 60-year-old woman was admitted because of fatigue. Physical examination revealed prominent peripheral lymphadenopathy, marked tonsillar swelling and hepatosplenomegaly. The leukocyte count was 68,900/microliters with 75% lymphoid blasts and 5% basophils. The karyotype of the blood cells was 46, XX, Ph1/47, XX, Ph1, +Ph1. The diagnosis of CML in blast crisis was made. After chemotherapy using adriamycin, cyclophosphamide, vincristine, and prednisolone (CHOP), lymphadenopathy and splenomegaly reduced and lymphoid blasts disappeared from the blood and bone marrow. At that time only single Ph1 (46, XX, Ph1) clone was detected in her bone marrow. Four months later, hematological relapse accompanied by lymphadenopathy occurred and DNA analysis of the blasts showed the rearrangement of bcr gene. The simultaneous chromosomal analyses of the blood, bone marrow and lymph node revealed that almost all cells examined had the karyotype "47, XX, Ph1, + Ph1". In spite of repeated chemotherapy the patient did not improve and died. This case suggests a relationship between lymphadenopathy and double Ph1 chromosomes in CML. PMID- 2246825 TI - [Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report]. AB - A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis. PMID- 2246827 TI - [Myelodysplastic syndrome with chromosomal abnormality of t(11;21) (q23;q22)]. AB - A 33-year-old woman was hospitalized because of bleeding tendency. Hemoglobin was 10.7 g/dl, white blood cell 2,100/microliters and platelet 2.1 X 10(4)/microliters. Bone marrow showed marked dysplasia of trilineage blood cells. Atypical blasts and monocytoid cells accounted for 14.5% in the myelogram. Cytogenetic study of bone marrow cells revealed translocation with t(11;21) in all of 20 metaphasic cells analyzed by G-banding method. A diagnosis of RAEB was made. Familial survey revealed that her elder brother died of acute monocytic leukemia (AMoL). The patient received small dose therapy of Ara-C and BHAC-DMP therapy, but a remission was not obtained. The patient's general condition deteriorated with infection, bleeding tendency and chronic hepatitis due to transfusions, therefore we have followed up the patient with prednisolone and red blood cell transfusion. It has become evident that some types of acute leukemia with monocytic features have a cytogenetic change at 11 q 23. But it is rare that RAEB with increased monocytoid cells has a cytogenetic change at 11q23. In addition, the patient's elder brother died of AMoL. This case is important in relation to cytogenetic change at 11q23 and hematopoietic abnormalities. PMID- 2246826 TI - [Transient dysfibrinogenemia and cerebral thrombosis following remission induction therapy for acute lymphoblastic leukemia]. AB - A 38-year-old female with acute lymphoblastic leukemia developed monoplegia of the left upper extremity following chemotherapy for remission induction consisting of vincristine, prednisolone, cyclophosphamide, adriamycin and methotrexate. Hemorrhagic infarction due to thrombosis of the right cortical vein was diagnosed by brain images using computed tomography and magnetic resonance imaging in addition to the clinical course. At this time, a plasma level of fibrinogen measured by the thrombin time method had decreased to 84 mg/dl, while its antigenicity was 276 mg/dl. There was no evidence of activation of the blood coagulation and fibrinolysis system nor of abnormal liver function. A mixing test with normal plasma disclosed the absence of an inhibitory factor against fibrin polymerization in her plasma. Fibrinogen levels as assessed by the thrombin time method recovered to the antigenicity level one and half months later. The discrepancy between the activity and antigenicity of fibrinogen indicated the occurrence of acquired dysfibrinogenemia, probably induced by antileukemic agents. Thus, it is suggested that dysfibrinogenemia is a possible cause of cerebral thrombosis in this patient. PMID- 2246828 TI - [Possible mechanisms of hematoma formation in the urinary tracts in a patient with idiopathic thrombocytopenic purpura]. AB - A 30-year-old female was admitted to our hospital complaining of hematuria and right flank pain in September, 1987. She had been diagnosed idiopathic thrombocytopenic purpura in 1980, and had similar symptoms before. Hematoma in the right ureter was demonstrated by retrograde pyelography and CT-scanning, and these symptoms improved within one month. Each activity of plasma clotting factors was within normal limits. Enzymatic studies of the urine revealed low values of plasmin-, urokinase-, and kallikrein-like activities in both excerbation and remission. These hemorrhagic tendencies might have been the result of marked thrombocytopenia: After bleeding into the urinary tracts began, the bleeding would tend to form hematoma because of elevated clotting activity; then hematoma would grow due to decreased urine fibrinolytic activities. This suggested that a decline of fibrinolysis in urine might have a promoting effect on the process of hematoma formation. PMID- 2246829 TI - [Clinical analysis on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, with plasma level of cytokine]. AB - We studied 10 patients with thrombotic thrombocytopenic purpura (TTP) and 5 patients with hemolytic uremic syndrome (HUS). Common cold symptoms were observed in 2 with TTP and 3 with HUS, and SLE was noted or suspected in 3 with TTP, and the onset was after operation in on with TTP and one with HUS. All TTP patients had coma and high fever. Renal failure was noted in 3 with TTP and their prognosis was poor. Seven patients with TTP and 4 patients with HUS survived. Autoantibody was highly positive in TTP but slightly positive in HUS. High molecular weight multimer of von Willebrand factor was decreased in 3 of 6 with TTP, platelet aggregating factor was positive in 4 of 6 with TTP, and microthrombus was observed in 7 of 8 with TTP. Tumor necrosis factor was increased in 5 of 9 with TTP and HUS, Interleukin-1 beta was increased in all TTP and HUS patients, and soluble interleukin 2 receptor and interferon alpha were also increased. Although plasma exchange was generally effective, some patients required combination therapy with steroids. We speculated that an autoimmune mechanism was involved in the on onset of TTP. PMID- 2246830 TI - [Management with antithrombin III concentrate in a pregnant woman with hereditary antithrombin III deficiency]. AB - Pregnant women with hereditary antithrombin III (AT-III) deficiency are frequently associated with thromboembolic disorders. We have treated a pregnant woman with hereditary AT-III deficiency, who had suffered from thromboembolic disorders at her past three gestations, with AT-III concentrate. Dosage of AT-III concentrate to maintain plasma AT-III activity over 80% was 3,500 units per week during second and third trimesters, but more frequent administration was necessary around delivery. In recent reports, pregnant women with hereditary AT III deficiency had been treated with heparin or warfarin except for during abortion and delivery, in which time AT-III concentrate was widely utilized. But the use of heparin or warfarin during gestation is occasionally harmful, AT-III concentrate should be chosen for management in pregnancy in women with hereditary AT-III deficiency. PMID- 2246831 TI - [Donath-Landsteiner antibody of the IgM class with anti-I specificity and possible efficacy of azathioprine therapy in paroxysmal cold hemoglobinuria: a case report]. AB - In October 1988, a 72-year-old man was admitted to Nagasaki Prefectural Shimabara Onsen Hospital because of hemoglobinuria on exposure to cold. On admission, the laboratory data were Hb 9.1 g/dl, LDH 2,337 U/L, and haptoglobin less than 6 mg/dl. The Donath-Landsteiner (DL) test was positive and serological tests for syphilis were negative. Anti-Coxsackie virus type A9 antibody titer was elevated. Accordingly, he was diagnosed as having paroxysmal cold hemoglobinuria (PCH) associated with viral infection. The DL antibody proved to be of the IgM class having anti-I specificity. The patient was treated unsuccessfully with prednisolone, but hemolysis was improved after azathioprine (AZP) therapy. PCH patients with DL antibody of the IgM class exhibiting anti-I specificity are very rare and only two patients including the present case have been reported in Japan. There has been no report on the efficacy of AZP in PCH, but our study suggests that AZP may have a potential therapeutic effect in some PCH patients. PMID- 2246832 TI - [Successful treatment of primary myelofibrosis by busulfan pulse therapy: report of a case]. AB - Idiopathic myelofibrosis is a disease of unknown cause characterized by systemic marrow fibrosis and extramedullary hematopoiesis. We report here a patient of myelofibrosis treated successfully by busulfan pulse therapy which was reported first by chang et al in 1988. The patient was a 62-year-old woman who was referred to us for anemia and hepatosplenomegaly in August 1984. Further examination established a diagnosis of idiopathic myelofibrosis. During the subsequent 4-year follow-up period without specific treatment in our outpatient clinic, there occurred gradual progression of anemia and hepatosplenomegaly with the spleen extending beyond the level of the umbilicus. In September 1988, she was initiated on 4-day pulse therapy of busulfan with a daily dose of 12 mg, which was repeated 10 times until July 1989. This was followed by marked improvement of anemia and hepatosplenomegaly. Post-treatment iliac marrow biopsy showed some reduction of reticulin fibers with increased hematopoietic elements as compared to pretreatment iliac marrow biopsy. The busulfan pulse therapy, therefore, appears to be a treatment of choice in idiopathic myelofibrosis. PMID- 2246833 TI - [Ileocolic intussusception in a recurrent non-Hodgkin's lymphoma; report of a case]. AB - The adult intussusception is rare. Here, we describe a case of an adult patient with ileocolic intussusception secondary to a recurrent lymphoma of the terminal ileum. The patient was a 42-year-old female, who had a history of the subtotal gastrectomy because of the primary gastric lymphoma. Eight months after the operation, she had a relapse in the abdomen and received the combination chemotherapy. She acquired the complete remission, but six months after the completion of the chemotherapy, she suffered from the right lower abdominal pain and diarrhea. Physical examination revealed a soft mass with tenderness in the right iliac fossa. Barium studies and abdominal computed tomography showed an ileocolic intussusception. At laparotomy, a 4.5 cm polypoid tumor was found in the terminal ileum and it passed through the ileocaecal valve to form an intussusception. Histologic examination disclosed the follicular lymphoma of medium-sized cell type. So far as we are aware, this is the first report of an adult patient with intussusception secondary to a lymphoma in Japan. PMID- 2246834 TI - [Malignant lymphoma diagnosed by the pericardial biopsy]. AB - The biopsy findings of malignant lymphoma involving the pericardium in a 69-year old male were reported. The initial presenting symptoms were heart failure followed by rapidly progressive complete heart block. Pacemaker was inserted. Chest roentgenogram showed a marked left pleural effusion. An echocardiogram demonstrated pericardial fluid. The diagnosis of lymphoma was suggested by gallium isotope study with markedly increased isotope uptake in heart, and was subsequently confirmed by pericardial biopsy. After chemotherapy the pleural effusion was decreased and the uptake of gallium disappeared. While the diagnosis of cardiac involved lymphoma was hard antemortem, experience in this case suggests that gallium isotope study and pericardial biopsy are helpful in establishing the correct diagnosis. PMID- 2246835 TI - [Successful treatment of adult T-cell leukemia with interferon-alpha-2b by systemic and local administration]. AB - A 59 years old woman, born in Fukuoka Prefecture, was admitted to our hospital in Aug, 1988 because of diarrhea, fever and skin eruption. Physical examination revealed systemic lymphadenopathy and hepatosplenomegaly. The white blood cell count was 11,200/microliters with 28% atypical lymphocytes with convoluted nuclei. Mild anemia, thrombocytopenia and hypercalcemia were also observed. Antibody against the adult T-cell leukemia (ATL) associated antigen in serum was positive. OKT 4/8 ratio was high. A diagnosis of ATL was made. Because of the complications of pneumonia and herpes simplex, systemic chemotherapy was not given, and interferon (IFN)-alpha-2b was intramuscularly injected daily from Oct, 1988, resulting in the disappearance of atypical lymphocytes and improvement of skin lesions. The effect of IFN therapy lasted for three months, followed by increase of atypical lymphocytes. Although the patient became refractory to systemic IFN therapy, local injection of IFN into a buccal tumor infiltrated with atypical lymphocytes resulted in its regression of size. In spite of continued administration of IFN, the patient died of pneumonia in Jan, 1989. PMID- 2246836 TI - [IgG subclasses of warm red cell autoantibodies in autoimmune hemolytic anemia]. AB - IgG subclasses (G-sub) of warm red cell autoantibodies (anti-Rs) were examined by means of antiglobulin test (DAT) using anti-IgG1, 2, 3, and IgG4 sera (Holland Red Cross) on 12 AIHA, and on 5 cases being DAT positive caused by alpha methyldopa (alpha MD). In 4 of 5 AIHA cases complicating SLE, the anti-Rs comprised not only IgG, but also IgA, IgM and C3; their G-sub were IgG1 + 2 in 2 and IgG1 + 2 + 3 + 4 in the other 2. In all of the 3 cases with idiopathic AIHA, anti-Rs comprised IgG alone (IgG1 alone, IgG1 + 3 or IgG1 + 2 + 3 in each one). All of the 5 alpha MD induced anti-Rs comprised IgG1 alone. Observation of the course of AIHA revealed that, although IgG3 tended to correlate with their anemia, this trend was not universal. Besides, the G-sub were not related to the anti-Rs titers. Furthermore, the immunological aberrations in patients with AIHA + SLE were found to be more complicated. PMID- 2246837 TI - [A case of venous hemangioma in the mediastinum]. AB - A thirteen-year-old boy was admitted to our hospital for further evaluation of abnormal shadow on chest film with a low grade fever. Laboratory findings revealed within normal value except for CRP. Chest film showed a smooth round mass in right middle mediastinum. In the CT scan, it was a well-defined round mass with low density in contact with sternum. With angiography, it had no relation to the great vessels. At operation, a coagulation was on the surface of a tumor. The tumor adhered to sternum and parietal pleura firmly and to aortic arch and thymus partly. But it was removed with ease "en bloc". It was dark red in color and upper part of was cystic, and lower massive. The tumor measured 9.5 x 5.0 x 5.5 cm and weighted 320 g. Histopathological findings demonstrated venous hemangioma proved by Masson trichrome stain. PMID- 2246838 TI - [A case of aneurysm of the inferior left ventricular wall]. AB - Aneurysms of the inferior left ventricular wall represent only a small fraction of all aneurysms that have been reported in surgical series. And in comparison to anterior left ventricular aneurysms, a comparatively higher percentage of reported inferior wall aneurysms was classified as false. A 73-year-old male was admitted for acute inferior myocardial infarction. Three weeks after admission, cardiac catheterization was carried out. Coronary arteriography revealed triple vessel disease and left ventriculography showed an aneurysm of the inferior left ventricular wall, whose feature near the mitral annulus was multiple fenestrations. Left ventricular aneurysmectomy and aortocoronary bypass grafting to the left anterior descending artery were simultaneously performed under cardiopulmonary bypass with moderate hypothermia. The pathological feature was a true aneurysm. The postoperative course was uneventful. PMID- 2246839 TI - [Indication for surgery in a patient with tuberculoma accompanied by chronic myeloid leukemia]. AB - Patients with chronic myeloid leukemia (CML) tend to suffer from non-reactive form of tuberculosis (TB) and often dissemination and death are the consequence when the blast crisis occurs. In those patients the eradication of pulmonary TB is essential to prolong their life. In a 58-year-old man with a tuberculoma and CML, right upper lobectomy was performed and was discharged 2 weeks later uneventfully. He succumbed to blast crisis 59 months after the onset of CML with no autopsy finding of recurrence nor dissemination of TB. The lobectomy in this patient was effective in preventing dissemination of TB. Controversy exists as to the indication for surgery but this case illustrates the effectiveness of surgery preventing the dissemination of TB in patients accompanying CML. PMID- 2246840 TI - [A case of primary leiomyosarcoma of the lung]. AB - We reported a case of 66-year-old female with leiomyosarcoma of the right lower lobe of the lung with the complaint of abnormal shadow of the chest roentgenogram. On December 2, 1987, partial resection was performed and the tumor was totally removed. Histological examination revealed primary leiomyosarcoma of the lung. By electron microscopic observation, pinocytotic vesicle was not observed, but myofilaments were observed in the cytoplasm. PMID- 2246841 TI - [Open heart surgery of a patient with Basedow's disease: a case report]. AB - A case of open heart surgery of Basedow's disease was presented. A 46-year-old female was admitted for mitral regurgitation with heart failure. She suffered from Basedow's disease ten years ago, and was treated with MMI. With this treatment, her thyroid function became normal and did well over the last four years. When open heart surgery (MVR) was performed, examination of her thyroid gland revealed mild hypothyroidism, and the operation could be performed without any thyroidal trouble. We conclude, in case of heart disease with Basedow's disease, the operation can be performed without any thyroidal trouble if the thyroid function is controlled well to euthyroid for a long term. Euthyroid condition lasted 4 years in this case. PMID- 2246842 TI - [Reconstruction of radicular arteries in the total replacement of thoracoabdominal aorta]. AB - A technique of reconstructing low intercostal, high lumbar arteries and Adamkiewicz artery is described to prevent paraplegia following operations on the thoracoabdominal aorta. A graft with a side branch is anastomosed proximally and a side branch to the distal thoracic aorta after reinforcement of the stumps under the partial bypass. Applying a clamp on the main graft, flow through the side branch and true lumen of the aneurysm is reestablished and bypass is terminated. The main graft, extended with a Y-graft, is anastomosed to common iliac arteries after proximal suture-ligation to perfuse the lower extremities. Splanchnic arteries are reconstructed according to DeBakey's technique which is followed by trimming of the thoracoabdominal aorta incising longitudinally with a clamp applied on the 1st side branch. Edges of the trimmed aneurysm are sutured to the slit of the graft from the right common iliac artery reconstructing intercostal, lumbar arteries and Adamkiewicz artery from the level of L2 upwards to T4 or more. As a final step, the graft is sutured to the 1st side branch allowing perfusion distally to the right lower extremity and the main graft to the splanchnic arteries and left lower extremity after division of a Y-graft right branch. The technique minimizes ischemic time for reconstruction of the aortic branches and enables complete reconstruction of the radicular arteries. PMID- 2246843 TI - [Injection into the vocal fold using a bronchofiberscope after esophagectomy]. AB - Postoperative recurrent laryngeal nerve paralysis is one of the most common complications after esophagectomy. We performed injection into the paralyzed vocal fold using a flexible bronchofiberscope 40 times in 27 patients. Injection was carried out without difficulty and morbidity like as therapeutic bronchoscopy after esophagectomy. This method is recommended to thoracic surgeons as an usefull technique in postoperative care after esophagectomy, especially for prevention of postoperative pulmonary complication. PMID- 2246844 TI - [A case of cardiomyoplasty with synchronous stimulated latissimus dorsi muscle]. AB - In December, 1988, a 57-year-old man sustained an acute myocardial infarction. He suffered from progressive cardiac failure, despite bed rest and intensive medical treatment. Finally, he developed hepatic and renal failure. Subsequent angiographic studies revealed the total occluded LAD (Seg. 6) and a large LV aneurysm. In January 1989, a left ventricular aneurysmectomy and cardiomyoplasty using the latissimus dorsi muscle were performed successfully. Two years after the operation, he is alive and well. PMID- 2246845 TI - [Clinical experience of adjustable pulmonary artery banding]. AB - Pulmonary artery banding has been a useful palliative procedure for infants with congenital cardiac anomalies associated with excessive pulmonary blood flow. We have experienced some cases that the band was not sufficient enough to reduce the pulmonary artery pressure in complex cardiac anomalies. Therefore, we developed a new adjustable pulmonary artery banding system which can be re-adjusted extrathoracically without reoperation. We used this system in seven infants with congenital cardiac lesions and obtained good results. PMID- 2246847 TI - [A new method for closure of median sternotomy: applications of a stapler system]. AB - Power driven staples were used in 20 patients for median sternotomy closure, and the staples were evaluated for clinical fixation. In each case four to six staples and two wires were used to secure closure. Clinically, in one patient prolonged sternal flail was observed, but this disappeared after six weeks. In the remaining 19 patients, good sternal fixation was secured. No cases required surgical procedures such as refixation of the sternum or removal of the staples. As a means of assessing the status of "backing out", which is a major cause of poor fixation, the backing out part of the staple leg was measured from lateral sternal radiographies. The ratio of the backing out portion to the staple leg, the backing out ratio (BOR), was calculated. The average BOR was found to be 32.7 +/- 21.4% (n = 102). The BOR was 70% or less in 91.2% of all staples, and 70% or more in 8.8%. The fragility of the sternum, poor sternal connection and inadequate technique to drive were suspected as factors accountable for backing out. In conclusion, the stapler system seems to be useful for sternal fixation and will become even more after improvement of the staple size and technical modifications to assure better connection at the driven site. PMID- 2246846 TI - [Consideration of management of type B dissecting aneurysms of the thoracic aorta: clinical comparative study between surgical and medical treatments]. AB - Between 1970 and 1989, 116 patients with type B dissecting aneurysms of the thoracic aorta were seen in our institution and affiliated hospitals. The patients were classified into 5 groups according to the acuity (acute vs chronic) and modes of therapy (surgical vs medical). Group I: 24 patients with acute B dissection were treated surgically during the acute stage. Group II: 21 patients with acute B dissection were initially treated with intensive medical therapy and followed by elective operation during the subacute stage. Group III: 22 patients with acute B dissection were treated medically. Group IV: 42 patients with chronic dissection were treated surgically. Group V: 7 patients with chronic B dissection were treated medically. The 5-year survival rates including early mortality were 70.5 +/- 9.4% for Group I, 88.9 +/- 7.5% for Group II, 68.3 +/- 11.2% for Group III, 64.6 +/- 8.4% for Group IV and 71.4 +/- 17.1% for Group V. The 5-year survival rates of Group II was significantly better than those of Group I, III and IV, respectively. The present data suggests that acute type B dissection without complications (bleeding, visceral or lower limbs ischemia) should be treated initially with intensive medical therapy and then followed by elective operation during the subacute stage, if the false lumen were not thrombosed. PMID- 2246848 TI - [Reoperation cases long after Rastelli operation: right ventricular outflow tract reconstruction by means of a xenograft non-valved patch]. AB - Two cases who underwent the new procedure of treatment for extracardiac conduit stenosis after Rastelli operation are reported. They had undergone Rastelli operation 11 and 12 years ago. Because of stenotic Hancock valve of the conduit, they were reoperated. A longitudinal incision was made anteriorly over the conduit and the conduit was dissected free. The sides and posterior half of the conduit bed were preserved. The roof of the new right ventricular outflow tract was formed using a xenograft pericardium patch. Their postoperative courses were smooth. PMID- 2246849 TI - [A case report of ball variance of Smeloff-Cutter prosthetic valve]. AB - A 37-year-old woman had undergone aortic valve replacement with Smeloff-Cutter prosthetic valve in 1967. She visited our hospital because of dyspnea and chest pain about 22 years after the operation. Severe aortic regurgitant murmur was audible and a chest X-ray demonstrated lung edema. A diagnosis was made of acute left heart failure due to prosthetic valve dysfunction, and emergency operation was performed. The Silastic ball was severely deformed and shrunken. Therefore, the ball was easily put off outside the cage. A St. Jude medical prosthetic valve was implanted. The postoperative course was uneventful. PMID- 2246850 TI - [Rupture of an infected vein graft in the course of mediastinitis following coronary artery bypass grafting: report of a case]. AB - A 51-year-old man developed a Staphylococcal mediastinitis and septicemia 23 days after coronary artery bypass grafting. He was initially treated with surgical debridement and closed irrigation with 0.5% povidone iodine solution. However, since the infection could not be eradicated by this method, an open packing method was subsequently required. Nineteen days after the diagnosis of mediastinitis, massive bleeding occurred due to rupture of an infected vein graft to the LAD. Although he went into profound hemorrhagic shock, suture ligation of the vein graft was successfully performed. The sternum was reapproximated 34 days after the initial debridement. Postoperative coronary angiograms revealed the patent vein grafts to the RCA and LCX, and PTCA was performed to the native stenosis of the LAD. The patient was discharged 5 months after the bypass operation and is now doing well 3 years postoperatively. Rupture of the heart or vessels in the course of postoperative mediastinitis is a very rare but highly lethal complication. We think that it is important to eradicate the infection as soon as possible to prevent the bleeding complication and that the decision as to which method, closed or open, should be employed, is crucial. PMID- 2246852 TI - Identification of the mutations in the parents of a patient with a putative compound heterozygosity for acute intermittent porphyria. AB - The molecular abnormalities responsible for acute intermittent porphyria were investigated in both parents of a girl who was retrospectively diagnosed as having a homozygous form of the disease. The mutations in the parents are different from each other and both of them correspond to previously identified G to A changes in the coding part of the porphobilinogen deaminase mRNA. These point mutations lead to the presence of a catalytically-defective but immunologically-reactive enzyme. Our results support the conclusion that the propositus girl may represent the first case of compound heterozygosity for acute intermittent porphyria alleles. PMID- 2246851 TI - A retrospective study of a patient with homozygous form of acute intermittent porphyria. AB - In 1964 a child with an exceptional form of porphyria was described; she excreted persistently excessive amounts of delta-aminolaevulinic acid, porphobilinogen and uroporphyrin in her urine from early childhood. The biochemical profile resembled that of acute intermittent porphyria (AIP). The child died at the age of 8 years. Reinvestigation of some urine samples by HPLC revealed differences in comparison with urines of other patients with AIP. The clinical picture characterized by porencephaly and severe retardation in development was completely different from that of AIP. Her mother suffered from AIP but the father never had attacks. Investigations on blood and urine samples of the father showed that he also was affected. Due to the early onset in the index patient, its persistent character, and the fact that both parents are affected we postulate retrospectively to have diagnosed a case of homozygous or a double heterozygous AIP, hitherto undescribed. PMID- 2246853 TI - Coexistent hereditary coproporphyria and congenital erythropoietic porphyria (Gunther disease). AB - We present data on one patient with an inheritance pattern for two porphyrias. From her mother she inherited the trait of hereditary coproporphyria; from both parents she inherited the trait of congenital erythropoietic porphyria (Gunther disease). Enzyme studies confirmed this new type of dual porphyria. PMID- 2246855 TI - Pyrimidine 5'-nucleotidase activity in normal and deficient human lymphoblastoid cells. AB - Two distinct pyrimidine 5'-nucleotidases (UMPH-1 and UMPH-2) have previously been detected in human erythrocytes; UMPH-1 is deficient in a haemolytic anaemia, while UMPH-2 is unaffected. Only the erythrocyte shows pathological effects in this disorder. Here we have studied lymphoblastoid cell lines from control and UMPH-1 deficient patients to determine whether UMPH-1 can be detected in lymphoblastoid cells and whether the deficiency of UMPH-1 results in any measurable metabolic effects. Both UMPH-1 and a UMPH-2-like activity were found to be present in control lymphoblastoid cells. UMPH-1 was undetectable in the patients' cells; minor but significant changes were found in the pyrimidine nucleotide and nucleoside pools in the cells. PMID- 2246854 TI - Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE). AB - The change in genomic DNA responsible for HPRT deficiency has been determined in a patient with urate overproduction and gout. In erythrocyte cell lysates, this patient had approximately 10% of normal HPRT enzyme activity and 26% of immunoidentical HPRT protein. Cultured lymphoblasts derived from this patient were used to extract mRNA. This was reverse transcribed to cDNA, which was then amplified using the polymerase chain reaction. The resulting DNA was cloned and the nucleotide sequence determined. In addition a portion of the sequence was derived from cloned double-stranded cDNA prepared by conventional first and second strand synthesis. A single nucleotide base change (a C----T transition) was detected, which predicts an amino acid substitution of isoleucine for threonine at amino acid 168 of the HPRT protein. The nucleotide substitution creates a BamHI site, confirming a restriction fragment length polymorphism previously reported in this patient. PMID- 2246856 TI - Analysis of abnormal urinary metabolites in the newborn period in medium-chain acyl-CoA dehydrogenase deficiency. AB - In order to determine which are useful early diagnostic markers for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we have analysed urine from an asymptomatic neonate. Profiling of urinary organic acids followed by peak confirmation by electron impact mass spectrometry revealed a high suberate/adipate ratio (greater than 1.0) and the presence of n-hexanoylglycine (HG). Acylcarnitine analysis by fast atom bombardment mass spectrometry (FAB-MS) was inconclusive, but FAB-MS/MS (tandem mass spectrometry) revealed diagnostic amounts of octanoylcarnitine and hexanoylcarnitine. Quantitative analysis of acylglycines by stable isotope dilution and chemical ionization mass spectrometry revealed a 30-fold increase in HG and increased suberylglycine, but no increase in 3-phenylpropionylglycine. PMID- 2246857 TI - Inherited metabolic disorders in Turkey. PMID- 2246859 TI - A new case of argininaemia without spastic diplegia in a Portuguese male. PMID- 2246858 TI - Heterogeneity of phenylketonuria at the clinical, protein and DNA levels. AB - The cloning of the phenylalanine hydroxylase gene and cDNA has potentially allowed the complete characterization of patients with phenylketonuria and already many mutations have been defined. Parents of patients now have the option of prenatal diagnosis. The 18 mutations defined so far indicate enormous heterogeneity not only within particular populations but also between populations. These mutations give little indication as to the locations of the amino acid residues important in enzyme function but one-third of the mutations are in exon 7 which may be indicating the importance of the region coded by this exon in the protein. PMID- 2246860 TI - Sudden death in an infant with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. PMID- 2246861 TI - Haloperidol-induced hyperammonaemia in a child with citrullinaemia. PMID- 2246862 TI - Atypical pyroglutamic aciduria: possible role of paracetamol. PMID- 2246863 TI - Genomic analysis of non-ketotic hyperglycinaemia: a partial deletion of P-protein gene. PMID- 2246864 TI - Simple and rapid detection of phenylketonuria mutation tightly linked to haplotype 2 by modified polymerase chain reaction. PMID- 2246865 TI - Putative genetic deficiency of 4-hydroxyphenylpyruvic acid dioxygenase in mice: a murine model for hereditary tyrosinaemia type III. PMID- 2246866 TI - A new variant of glutaric aciduria type II: deficiency of beta-subunit of electron transfer flavoprotein. PMID- 2246867 TI - ACCESS: keystones for school health promotion. AB - This article provides a perspective on the three elements that traditionally constitute school health programs in the U.S. and describes a new model called ACCESS. Consisting of five major keystones, ACCESS provides an organizational structure for planning, implementing, and evaluating school health promotion programs. In addition, the model provides a reference point for international comparisons of school health. PMID- 2246868 TI - Australia: perspectives in school health. AB - Australia, a predominantly industrialized, urban-based nation, has health problems similar to most developed countries. The federal and state relationship in Australia perpetuates a similarity between programs and practices across the country, especially in health and education. During the past decade, several research programs related to the primary prevention of Australia's major health issues were conducted. Determinations of program success have been established from these programs and their international counterparts. Guidelines and principles are discussed in the context of two recent health initiatives and are presented as indicative of current developments in Australia. For this article, a one-in-five sample of South Australian schools was surveyed regarding the health education programs and practices. Survey results and two initiatives are presented against a background of Australian health data. PMID- 2246869 TI - Canada: perspectives in school health. AB - Because education is the individual responsibility of 10 provinces and two northern territories, the quality of school health varies greatly across Canada. However, planned major events in the past few years have served as catalysts to begin considering a comprehensive approach to school health. The value of coordinating instruction in health with school services and the community environment is beginning to be realized. These long "overdue" developments are reviewed and summarized. PMID- 2246870 TI - Chile: perspectives in school health. AB - The leading health problems of children and adolescents in Chile is reviewed. The Chilean educational system and how the system addresses its principal health problems are described. A school health program is described as well as other educational programs designed and developed by nongovernmental institutions which have a smaller coverage. Current research studies regarding growth and development, child morbidity, nutritional level, and mental health studies are reviewed. In addition, principal challenges that include developing more efficient ways of referring children, enriching the curriculum and teacher training, assigning school hours for health teachers, and enlarging coverage of the health care evaluation programs are outlined. Of special importance is developing prevention programs for parents and children using school and community leaders to prevent health problems in areas such as human sexuality education, decision-making, social abilities, and alcohol and drug abuse. Main efforts should be directed toward low-income families and children to improve life conditions. PMID- 2246871 TI - England and Wales: perspectives in school health. AB - The main roots of health care and health education for young people in the United Kingdom are described. Contributions of the National Health Service to health screening and developmental assessment are described, primarily through the function of school health services. The development and future potential for effective school health education also is considered in the light of the impending introduction of a new national curriculum. The evaluation of the concept of the "health promoting school" is highlighted as a key area for future development, together with more emphasis on achieving a balance between health enhancement and educational outcomes to school health education. Greater priority for evaluation of school health education also is advocated. PMID- 2246872 TI - Federal Republic of Germany: perspectives in school health. AB - In the Federal Republic of Germany, responsibilities for health and education are held by the 11 German states. Particularly in the health system, a number of tasks are delegated to private organizations under governmental control. In this review, general characteristics of both the public health and education systems are delineated. An overview of school health programs, including instruction, health services, environment, and school-community relations, and school-based research, also are presented. PMID- 2246873 TI - Japan: perspectives in school health. AB - In Japan, the original Law of School Health was established some 65 years ago to improve the environment and to prevent infectious diseases in school. Most recently, new environmental problems and behavioral issues have emerged. In addition to environmental health and health education, a major aspect of school health has been the development of a mass screening system both to detect present problems and to prevent adult diseases. In this article, the school health system in Japan is described and the application of mass screening by reference to heart disease as detected in Shimane Prefecture is illustrated. In the future, mass screening may be combined with a computer-based analysis system for managing data on new kinds of problems. New disciplines may become involved and improved programs developed, based on the lessons already learned from mass screening. PMID- 2246874 TI - Mexico: perspectives in school health. AB - The school health program in Mexico, directed by the Office of School Hygiene (la Unidad de Higiene Escolar), is in a state of flux. The program will change substantially if an initiative between the national offices of health and education is enacted. The initiative would establish a national commission to be replicated at state, county, and district levels. Commissions would oversee integration of the health services component, social participation, and research into the school health program which currently only focuses on health instruction and a healthy school environment. The initiative would restore and improve a former model that incorporated health services as a part of the school health program. The history of the school health program, which can trace its roots to 1861 and President Benito Juarez, is provided. PMID- 2246875 TI - The Nordic countries: perspectives in school health. AB - Denmark, Finland, Iceland, Norway, and Sweden constitute a geographical and cultural entity referred to as the Nordic countries. These countries all enjoy a high standard of living, and the health of their children can be characterized as good in comparison to that of earlier generations and that of many other nations. In the Nordic countries, school health services constitute a compulsory component of school systems and are free to all students. During the past decade, the World Health Organization's "Health for All by the Year 2000" goals were adopted, including goals for Nordic school health programs. However, school health programs are a neglected area compared to the emphasis placed on other health services. Reasons to improve health education and health services provided within the school setting in the Nordic countries are presented. Several interpersonal, intrapersonal, and organizational barriers to a more active health promotion effort also are identified. PMID- 2246876 TI - People's Republic of China: perspectives in school health. AB - As the population growth rate of the People's Republic of China slows, the health of its schoolchildren is improving. A three-tiered health system incorporating traditional and modern medicine is reflected in an educational curriculum that is based on community involvement and, more recently, on prevention. The Chinese Ministry of Public Health focuses on three main issues affecting the health of schoolchildren: poor vision (myopia), dental care, and nutrition. Vision problems are predominant among Chinese students and are addressed through treatment, improved architectural design of school buildings, and lessening of homework assignments. Dental care is addressed through treatment and education. Nutrition, a problem primarily among rural schoolchildren, is addressed through vitamin and mineral supplements and community involvement. PMID- 2246877 TI - Taiwan, R.O.C.: perspectives in school health. AB - Continuous economic development and evolving social systems have created unique challenges for school health personnel in Taiwan. Due in part to economic growth and an improving health care system, average life expectancy has increased markedly for males and females since 1950. Traditional leading causes of death such as pneumonia, tuberculosis, and gastroenteritis have been replaced by accidents, neoplasms, and cardiovascular diseases. Schoolchildren suffer from various disorders that include hepatitis B, dental caries, and health problems related to scholastic pressure such as myopia, anxiety, and depression. However, new problems such as violence, substance use, and teen-age pregnancy may develop in the future. In response to the challenge, an extensive school health program has emerged that emphasizes school health instruction, school health services, and a healthful school environment. Increased attention has focused on teacher preparation in health education, and a cooperative approach to school health promotion emphasizes school, community, and interagency cooperation. Prompted by the establishment in 1980 of the Graduate Institute of Health Education, National Taiwan Normal University, school-based research initiatives have increased dramatically. Eighteen recommendations for further improvement are offered. PMID- 2246880 TI - A perspective on international school health education research. AB - The scope and content of school health education research conducted from 1984 1987 in countries outside the U.S. are examined. Both published and unpublished research were requested from sources identified by the American School Health Association's Council on International Health. One hundred eighty-eight studies from 31 countries were reviewed and categorized. Countries that publish journals devoted to school health offer more opportunities for publishing research. Analysis of the studies revealed that individuals involved in school health face similar problems regardless of country. Cross-country comparative studies serve as models for future research. PMID- 2246878 TI - United States: perspectives in school health. AB - An overview is presented of school health programs being conducted in the U.S. as well as the U.S. education system. Major health problems of youth are identified and initiatives to improve the health of school-aged youth are reviewed. With the start of the new decade, it will be important to use and disseminate the findings from ongoing school health programs and research projects, to address the growing social issues for children and adolescents that directly affect their physical health, and to broaden the scope of school health to include issues of psychological or mental health, issues related to social competencies, dysfunctional family lives, or major life events. PMID- 2246879 TI - The World Health Organization: school health initiatives. AB - The United Nations and its family of operational agencies have existed for almost five decades. For school health personnel, to understand how these agencies operate--in particular, the World Health Organization (WHO)--is worthwhile. To understand how WHO influenced the practice of health education for school-aged youth, some critical events that have occurred during the past five decades are reviewed and several current and future activities are identified and described. PMID- 2246881 TI - Nonuniform blood flow in the canine left ventricle. AB - In order to investigate the relationship between coronary perfusion pressure and blood flow distribution in the left ventricle (LV), we measured myocardial blood flow in small regions using radioactive microspheres in six anesthetized, open chest dogs. Mean coronary perfusion pressure (CPP) was controlled with a femoral artery to left main coronary artery shunt which included a pressurized, servo controlled blood reservoir. In each dog, we measured flow in 192 regions of the LV free wall (mean weight per region = 206 +/- 38 mg) at different perfusion pressures. At CPP = 80 mm Hg, blood flow to individual regions varied fourfold (0.30 to 1.18 ml/min/g; relative dispersion (RD) = 21.8 +/- 2.3%). At CPP = 50 mm Hg, flow varied over sevenfold (0.08 to 0.60 ml/min/g; RD = 42.8 +/- 10%; P less than 0.01 vs 80 mm Hg). This relationship between flow variability and CPP was present within individual LV layers as well between layers and is much higher than the error associated with the microsphere technique. We conclude that blood flow to small regions of the LV is markedly nonuniform. This heterogeneity becomes more profound at lower CPP. These findings suggest that (1) global measurements of coronary flow must be interpreted with caution, and (2) even in hearts with normal coronary arteries some regions of the LV are more susceptible to ischemia than others. In addition, these findings may help explain the patchy nature of myocardial damage that occurs following periods of low coronary pressure or inadequate myocardial protection during cardiopulmonary bypass. PMID- 2246882 TI - Gastric emptying and myoelectric activity following Roux-en-Y gastrojejunostomy. AB - The purpose of this study was to compare gastric emptying and Roux myoelectric activity in a canine model. Four dogs underwent truncal vagotomy, antrectomy, and 40 cm Roux-en-Y gastrojejunostomy, with placement of serosal electrodes. Following recovery, gastric emptying was determined scintigraphically with a radiolabeled solid meal, and fasting and fed small-bowel myoelectric activity was obtained. Gastric emptying was markedly slowed compared to control unoperated animals (202 +/- 91 versus 46 +/- 12 min; P less than 0.05). Slow wave frequency declined in the Roux limb compared to the duodenum (14.2 +/- 0.4 versus 18.0 +/- .06 counts per minute; P less than 0.01). No gradient in slow wave frequency was observed in the Roux limb, although one animal was noted to have reversed propagation of slow waves in the proximal Roux limb. Migrating myoelectric complexes (MMCs) were coordinated between the Roux limb and jejunum distal to the enteroenterostomy, but not with the duodenum. Periodicity of the MMCs was different in the Roux limb and duodenum (98.6 +/- 6.3 versus 138 +/- 17.5 min; P less than 0.05). None of the animals converted to the fed myoelectric pattern with a 272 kcal meal (MMC periodicity in the Roux limb = 99 +/- 10 min postprandially, P = N.S.). These quantitative and qualitative alterations in myoelectric activity may contribute to the observed delay in gastric emptying following Roux-en-Y gastrojejunostomy. PMID- 2246883 TI - Donor-specific tolerance permits burn allografting without increased sepsis. AB - Early excision and allografting of massive burns is beneficial. However, chronic immunosuppression, utilized to prolong allograft survival, increases the potential risk of infection. We have previously shown long-term skin allograft survival in mice with a 30% total body surface area (TBSA) burn by inducing donor specific tolerance (DST) using only perigrafting administration of antithymocyte globulin (ATG) and donor bone marrow (DBM). Chronic immunosuppression is avoided. This study tests whether induction of DST compromises host resistance to infection. Resistance to a septic challenge created by cecal ligation and puncture (CLP) 10 days after a 30% TBSA burn was investigated in the following groups of mice: [table: see text] Positive blood cultures were documented for 97% of mortalities. Burn excision and grafting significantly (P less than or equal to 0.05) decreased mortality. No increased mortality was seen in allografted mice receiving ATG or ATG and DBM compared to isografted mice receiving no immunosuppression. These studies suggest that skin allografting with DST may permit the benefits of burn excision without the risks of infection seen with chronic immunosuppression. PMID- 2246884 TI - A technique for isolated liver perfusion in the rat with survival and results of cytotoxic drug perfusion on liver tumor growth. AB - The toxic side effects of many chemotherapeutic agents prevent their use in high concentrations. Isolated perfusion techniques have been used most commonly for malignancies involving the extremities, but recently also for irresectable liver tumors. This paper describes a technique for in vivo isolated liver perfusion for 30 min with oxygenated blood through the portal vein and hepatic artery simultaneously. There was a 14% mortality rate. There was some initial hepatocellular death, which resolved quickly and did not seriously affect liver function. There was only a small leak from the perfusion system to the systemic circulation. We tested the system on an experimental liver tumor from a colonic adenocarcinoma. Perfusion with added 5-FU in a toxic dose of 70 mg/kg to the medium significantly retarded tumor growth evaluated 10 days after perfusion compared to rats perfused without 5-FU. This model closely resembles the technique applied clinically and will enable further work on effects of perfusion in an experimental rat liver tumor model. PMID- 2246885 TI - Immunorestorative effects of reimplanted splenic tissue and splenosis. AB - Different immune functions were analysed in detail in 41 patients who had been splenectomized after a traumatic rupture of the spleen within four years after surgical intervention. Patients were assigned to one of the following groups as judged by liver/spleen scintigraphy: (1) patients with reimplanted splenic tissue, (2) patients with splenosis, and (3) patients without splenic tissue. Leukocytosis and an increased number of total lymphocytes as well as B-cells were observed in patients of all groups. In addition, the number of circulating T suppressor cells was significantly increased in patients with no detectable splenic tissue. In contrast, serum concentrations of immunoglobulins and complement components were in the normal range; similarly, phagocytosis associated functions of the patients' neutrophils and monocytes were found to be unimpaired (chemiluminescence and particle uptake). However, in all groups of splenectomized patients a deficiency in specific serum opsonic activity against a strain of Escherichia coli (O:102, H:6) could be detected. We conclude that neither splenosis nor autologous reimplantation of splenic tissue restores opsonic deficiency caused by splenectomy. PMID- 2246886 TI - The effect of interleukin-2 administration on wound healing in adriamycin-treated rats. AB - Adriamycin (doxorubicin hydrochloride), an effective chemotherapeutic drug, is also a potent inhibitor of wound healing. Conversely, certain polypeptide growth factors are capable of stimulating fibroblasts to secrete collagen, thus enhancing wound healing. The purpose of this study was to determine if interleukin-2 (IL-2), a T-cell growth factor, could reverse the wound healing deficit caused by Adriamycin. Adriamycin treatment caused a significant decrease in wound-breaking strength (P less than 0.005). IL-2 administration increased wound-breaking strength in Adriamycin-treated animals (2126 g vs 1549 g, P less than 0.005). In control animals, IL-2 did not increase wound-breaking strength significantly (2708 g vs 2608 g, P greater than 0.1). Histologically, wounds from Adriamycin-treated animals were less cellular, demonstrated less collagen in the dermis, and a lesser degree of capillary ingrowth. The number of fibroblasts in the dermal layer was increased in animals receiving IL-2. Control rats gained an average of 1.4% of their original body weight, while Adriamycin-treated rats lost an average of 19% of their original body weight (P less than 0.0005). IL-2 administration did not influence weight loss or gain. Hematologically, animals receiving Adriamycin had lower hemoglobin and hematocrit values and higher platelet counts. There were no differences in total white blood cell counts; however, animals receiving Adriamycin showed a predominance of polymorphonuclear leukocytes and a relative decrease in lymphocytes. Animals receiving IL-2 demonstrated a significant eosinophilia. (1) Adriamycin impairs normal wound healing. (2) Interleukin-2 administration improves the wound healing impairment caused by Adriamycin. (3) Interleukin-2 appears to increase infiltration of inflammatory cells, fibroblasts, and capillaries into the wound, which may account for the observed increase in wound breaking strength. PMID- 2246887 TI - Iodine toxicity secondary to continuous povidone-iodine mediastinal irrigation in dogs. AB - Mediastinitis is a devastating complication following median sternotomy. Continuous povidone-iodine (PVP-I) irrigation has been advocated as therapy because of its broad antimicrobial spectrum and its apparent safety. However, several recent clinical reports have warned of suspected local and systemic iodine toxicity. The purpose of this study is to determine if significant amounts of iodine can be absorbed systemically via the mediastinum, and if so, what toxicity (local and/or systemic) may result. PVP-I (0.5%) was continuously irrigated into the pericardial sacs of three dogs via catheters for 48 hr. Serial serum and urine iodine levels were determined. The serum steady-state concentration (Css), the rate elimination constant (k), the urinary clearance (Cl), and the serum half-life (t 1/2) for iodine were assessed. Serum electrolytes, Bun, Cr, and arterial pH were measured to assess systemic iodine toxicity. Tissue samples of the heart, pericardium, liver, and kidney were examined histologically for evidence of local or end-organ iodine toxicity. This study demonstrated that the absorption of iodine during continuous mediastinal irrigation with PVP-I follows zero-order pharmacokinetics, just as if it were being given by continuous intravenous infusion. The baseline serum iodine concentration was 145.9 +/- 64.3 micrograms/dl, Css was 29,290 +/- 101.4 micrograms/dl, k was 0.0996 +/- 0.009/hr, Cl was 872.4 +/- 119.3 ml/hr, and t1/2 was 6.22 hr. Urinary excretion of iodine increased in proportion to the serum iodine. Measured serum chloride increased in a linear manner (r = 0.949), while serum Na, K, Bun, Cr, and pH were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246888 TI - Calcitonin gene-related peptide increases coronary flow and decreases coronary resistance. AB - Calcitonin gene-related peptide (CGRP) is a potent vasodilator, but its effects on in situ ventricular function are unknown. We studied effects of intracoronary CGRP (100, 200, and 600 pmole/min, for 10 min) in 21 open-chest chloralose anesthetized dogs. Systemic, pulmonary, left ventricular (LVP), central venous, and pulmonary capillary wedge pressures were continuously monitored. Left ventricular wall thickness (WT) and circumflex coronary blood flow were also measured. CGRP was infused into the proximal circumflex artery. During CGRP infusion there were no changes in heart rate, cardiac index, pulmonary artery pressure, or systemic vascular resistance, no percentage change in ventricular WT, and no changes in dWT/dt, peak dP/dt, or the slope of end-systolic points on WT/LVP loops. But there were significant changes in coronary flow (CQ), coronary resistance (CRES) and mean arterial blood pressure (MAP) from control (C)* (P less than 0.05). (table; see text) CGRP is a potent coronary artery vasodilator causing notable dose-dependent decreases in coronary resistance and a rise in myocardial flow, despite a decreased MAP (all P less than 0.05). CGRP does not affect ventricular contractility in vivo. PMID- 2246889 TI - Plasma albumin repletion after transfusion with polymerized hemoglobin. AB - Pyridoxalated polymerized hemoglobin (PPHG) has promise as a blood substitute for transfusing patients with hemorrhage. Exchange transfusion with PPHG depletes plasma proteins. The purpose of this study was to determine if, during the early repletion of intravascular proteins, albumin was transported from the interstitium of skin or skeletal muscle into the vascular compartment. PPHG was prepared from stroma-free human hemoglobin (100-120 mg/ml). The Hct of anesthetized rats dropped from 42 +/- 4% to 10 +/- 1% after exchange transfusion. Immediately postexchange plasma albumin declined from 24 +/- 2 to 6 +/- 3 mg/ml. Five hours postexchange transfusion plasma albumin had doubled and the skin and skeletal muscle albumin content was 80% of control. These data indicate that a shift of interstitial albumin from skin and skeletal muscle can rapidly replace plasma protein deficits after massive transfusion with PPHG. PMID- 2246890 TI - Plasma clearance and tissue distribution of recombinant human platelet-derived growth factor (B-chain homodimer) in rats. AB - 125I-labeled human recombinant platelet-derived growth factor (B-chain homodimer; rHuPDGF-BB) was intravenously injected into male rats, and plasma clearance and tissue distribution of total and acid-insoluble radioactivity were determined. Insoluble radioactivity was rapidly cleared from plasma in a biphasic manner with estimated distribution and elimination half-lives of 5.2 and 68 min, respectively. Less than 10% of the injected radioactivity remained in plasma at 1 hr after injection. rHuPDGF-BB was widely distributed throughout body tissues. However, acid-insoluble radioactive concentrations greater than those in plasma were only observed in liver, kidneys, and spleen. The radioactive concentration of most tissues declined rapidly between 1 and 4 hr but increased in the intestinal contents. Radioactive concentrations decreased in all tissues and intestinal contents at 8 and 24 hr. Urine samples collected at the latter interval showed that 39% of the dose was excreted by the kidneys in an acid soluble form. These results suggest that the rapid clearance of rHuPDGF-BB from plasma is the result of widespread tissue distribution, metabolism by the liver, and excretion by the kidneys. In this respect, the pharmacokinetic behavior of rHuPDGF-BB resembles that of other lymphokines and growth factors that have recently been studied. PMID- 2246891 TI - A model of persistent partial hindlimb ischemia in the rabbit. AB - An animal model of resting limb ischemia in the rabbit was developed and studied. Anesthetized rabbits underwent unilateral common iliac artery (CIA) division, allowing comparisons between an experimental (ischemic) and the contralateral control limb in the same animal. The time course and severity of the ischemic insult were measured by quantitating muscle blood flow in seven muscle groups using 57Co-radiolabeled microspheres, limb femoral arteriovenous oxygen differences (AVDO2), and limb arterial pressure. Nine of 20 animals had objective evidence of functional limb impairment judged by abnormal resting posture and/or abnormal gait. Muscle blood flow in the experimental limbs became significantly less than blood flows of corresponding contralateral muscle groups (P less than 0.05) when measured at 1 week after CIA division. By 17 days, mean muscle blood flow had returned to within 82.5% of that of the control limb. AVDO2 increased from 4.8 +/- 0.99 to 8.13 +/- 2.26 ml O2/dl blood following CIA division and remained persistently greater than the control limb value until Day 31. Limb arterial pressure decreased markedly after CIA division and remained significantly depressed beyond 6 weeks when the study was terminated. The reasons for the differential time courses of these parameters of blood flow are discussed. Common iliac artery division in the rabbit appears to produce persistent, partial ischemia at least 17 days in duration, allowing in-depth study of the effects of persistent limb ischemia on muscle cell function in the laboratory setting, as well as permitting the assessment of various therapeutic manipulations for the treatment of prolonged muscle ischemia. PMID- 2246892 TI - The accuracy of fine needle aspiration biopsy for flow cytometric determination of tumor DNA content. AB - The use of fine needle aspiration (FNA) to obtain a diagnosis of malignancy is established in the practice of oncology, but there is little information on its accuracy in sampling tumor DNA content. We therefore compared flow cytometric DNA data obtained from FNA-derived samples with that obtained after digestion of the same murine tumor from which the aspirates had been taken. Fifteen female C3Hf/Kam mice were implanted with MCA-29 tumor cells from the same source tumor. MCA-29 is a multiploid mammary adenocarcinoma with two aneuploid populations (DNA Index of A = 1.67, B = 1.89). The tumors were grown to a mean size of 8.6 mm. After sacrifice, three FNAs were performed on each tumor, following which the whole tumor (WT) was excised and homogenized. All FNA and WT samples were digested with 0.04% pepsin and the nuclei stained with propidium iodide in preparation for flow cytometry. DNA histograms of the aspirates were compared with the corresponding WT histograms. Any single FNA detected population A in all (100%) cases and detected the less prominent population B in 94.3% of instances. Any single FNA was able to detect the same populations that were present in the whole tumor in 95.4% of cases, while the set of three aspirates matched the corresponding WT in 100% of cases. We conclude that FNA DNA histograms are accurate for the assessment of ploidy, but that in order to ensure detection of all tumor populations present, multiple aspirates are needed. PMID- 2246893 TI - Calcium antagonists retard extracellular matrix production in connective tissue equivalent. AB - Hypertrophic and keloid scars are characterized by the overproduction of extracellular matrix collagen and proteoglycans. Because cellular secretion of macromolecules is known to be a calcium-dependent process, we have examined the effect of calcium antagonists on the rate of incorporation of [3H]proline into protein and Na235SO4 into sulfated glycosaminoglycans. Experiments were carried out in vitro using uniaxially oriented mammalian fibroblast-populated collagen matrices which exhibit many histoarchitectural features of scar matrix. We observed that nifedipine and verapamil in sufficient concentrations inhibited the incorporation of proline into extracellular matrix protein. The concentration range studied was 1 to 100 microM. Cobalt chloride (200 microM) had a similar effect on proline incorporation, but enhanced the incorporation of sulfate into extracellular matrix glycosaminoglycans. We conclude that cellular calcium metabolism appears to regulate extracellular matrix production and that hypertrophic disorders of wound healing may respond to therapy with calcium antagonist drugs. PMID- 2246894 TI - The evolution of the scrotum: a new hypothesis. AB - The adaptive significance of the scrotum is unresolved after more than 60 years of debate and experimentation. The "training hypothesis" introduced here suggests that testicular descent is a mechanism for improving sperm quality. The hypothesis proposes that: (1) testicular descent decreases blood supply to maturing sperm cells, (2) sperm mitochondria respond to the resulting oxygen stress by enhancing their enzymatic machinery for oxidative metabolism, as do oxygen-stressed muscle cell mitochondria, and (3) the resulting increase in aerobic fitness of sperm cells is advantageous in inter-ejaculate competition. The hypothesis suggests that there is a quantity-quality trade-off in sperm production, where taxa with internal testes produce large volumes of low-quality sperm while taxa with scrotal testes produce smaller volumes of higher-quality sperm. PMID- 2246895 TI - The Gibbons speciation mechanism. AB - A mechanism of sympatric speciation first proposed by Gibbons (1979, Am. Nat. 114, 719-741) is analyzed and submitted to computer simulation. It is found that, in its original form, the mechanism does not bring about reproductive isolation, but that with relatively minor modification, it may be made to work as claimed. PMID- 2246896 TI - A comparison of the parameter estimating procedures for the Michaelis-Menten model. AB - The performance of four parameter estimating procedures for the estimation of the adjustable parameters in the Michaelis-Menten model, the maximum initial rate Vmax, and the Michaelis-Menten constant Km, including Lineweaver & Burk transformation (L-B), Eadie & Hofstee transformation (E-H), Eisenthal & Cornish Bowden transformation (ECB), and Hsu & Tseng random search (H-T) is compared. The analysis of the simulated data reveals the followings: (i) Vmax can be estimated more precisely than Km. (ii) The sum of square errors, from the smallest to the largest, follows the sequence H-T, E-H, ECB, L-B. (iii) Considering the sum of square errors, relative error, and computing time, the overall performance follows the sequence H-T, L-B, E-H, ECB, from the best to the worst. (iv) The performance of E-H and ECB are on the same level. (v) L-B and E-H are appropriate for pricesly measured data. H-T should be adopted for data whose error level are high. (vi) Increasing the number of data points has a positive effect on the performance of H-T, and a negative effect on the performance of L-B, E-H, and ECB. PMID- 2246897 TI - Temperature regulation of marine mammals. AB - A mathematical model of heat loss from an aquatic animal to the surrounding water is presented. Heat is generated in metabolically active tissues and distributed by circulating blood and by conduction. The time dependent radial temperature profile of the animal is numerically solved from heat transfer equations by a computer. The model is applied to large whales, porpoises, and seals. For the whales, blood circulation to the dermal layer below appendage and body skin surfaces proved to be essential for sufficient heat dissipation. When decreasing the blood flow below a certain value (dependent on sea temperature and whale activity) the large whales would overheat. Blubber thickness was found to be of minor importance in whale thermoregulation, because the blubber coat can be bypassed by blood circulation. On the other hand, it is in general not possible for small porpoises and seals to stay warm in the coldest waters using normal mammalian resting metabolic rates, even if the peripheral circulation is shut off (or artery-vein heat exchangers used). Heat loss can be reduced if the outermost tissue layers are allowed to cool. This is achieved by minimizing convective radial heat flow via the circulation. (For large whales even minute radial blood flow raises the muscle temperatures to the core temperature level.) Seasonal acclimatization of harbour seals is explained by changes in their effective insulation thickness. Differences in whale activity induce changes in the temperature profile mainly within the first few centimeters from the skin surface. These superficial temperatures, if known, could be used to estimate whale metabolic rates. Since they drop close to the sea water temperature within minutes after whale death, the measurements should be done of live whales. PMID- 2246898 TI - Extracellular matrix interactions: sulfation of connective tissue polysaccharides creates macroion binding templates and conditions for dissipative structure formation. AB - Evidence is now accumulating that the post-polymer modification process of sulfation of connective tissue polysaccharides is primarily to provide an interactive macroion for enthalpic interactions rather than influence thermodynamic non-ideality which primarily affects water distribution in biological systems. Metabolic energy considerations also distinguish these physicochemical classifications. Thermodynamic non-ideality is embodied in the carboxyl group and polysaccharide chain which are energetically favoured in biosynthesis, whereas considerable energy input is required for sulfation. The sulfation process gives rise to macroions, with a wide variety of negative charge patterns, that may participate in heterotypic macromolecular interactions. This partial informational specificity is discussed in terms of evolutionary flexibility of the extracellular matrix as rationalized on the qualitative aspects of dissipative structure formation. The concept of multiple binding interactions of varying specificity associated with connective tissue polysaccharides raises the awareness of a more random, less highly ordered, extracellular matrix as compared to the tight machine-like organization generally found for processes in the cell. This is discussed in terms of the physiological adaptation and development of multicellular-tissue systems. PMID- 2246899 TI - Feedback loop between kinship and dominance: the macaque model. AB - There is growing evidence that macaque social systems represent sets of coadapted traits in which strength of hierarchies and degree of nepotism covary. A framework is developed to explain the link between dominance and kinship phenomena, assuming that power brought by alliances among non-kin is allometrically related to those involving relatives. This can account for the type of social relationships observed in "despotic" systems vs. "egalitarian" ones. When social bonds are mostly founded on kinship, lineages are closed and social power generated by coalitions among relatives may reach high levels; social power frequently outweighs the fighting abilities of single individuals, and asymmetry of dominance between group members may be marked. When lineages are more open, social bonds and alliances are less kin-biased, social relationships are more equal, and as the influence of coalitions is less important, the individual retains a certain degree of freedom in relation to the power of kin networks. Acknowledging that the balance between individual and social power is not set at the same level across different species can explain a number of variations in rules of rank inheritance and relative dominance of males and females among macaques. The framework illustrates how epigenetic processes may shape complex features of primate social systems, and offers opportunities for testing. PMID- 2246900 TI - Quantification analysis of 5'-splice signal sequences in mRNA precursors. Mutations in 5'-splice signal sequence of human beta-globin gene and beta thalassemia. AB - Concerning the signals which direct excision of introns from mRNA precursors in higher eukaryotic genes, consensus 9-nucleotide sequence, (CA)AG/GT(AG)AGT, has been proposed with the 5'-splice site, but actual 5'-splice site sequences differ from it in a greater or lesser degree. We analyzed 5'-splice site sequence of human beta-globin gene by quantification method (categorical discriminant analysis) proposed previously. Analysis of 13-nucleotide sequences and deleted sequences showed that 9-nucleotide sequences in the consensus region are almost sufficient to define 5'-splice signal. To confirm this view, we examined a number of beta-globin mutant genes, where nucleotide changes occur at the authentic 5' splice site of the first intron and cause beta-thalassemia phenotype. Our method could explain why such mutations abolish the 5'-splice site and cryptic 5'-splice sites are activated. PMID- 2246901 TI - Evolutionary relationships between "Q-type" photosynthetic reaction centres: hypothesis-testing using parsimony. AB - Hypotheses concerning the evolutionary relationships between "Q-type" photosynthetic reaction centres are tested using amino acid parsimony analysis of subunit sequences and an alignment based on dot matrix comparisons. Strong evidence is found for independent gene duplications having produced the L and M subunits of the photosynthetic purple bacterial reaction centre and D1 and D2 of Photosystem-II. Much support is also found for the L and M subunits of the green filamentous bacterium Chloroflexus aurantiacus arising from the same gene duplication as the purple bacterial subunits, suggesting there was an ancestral bacterial heterodimeric reaction centre. These conclusions caution against over extrapolation from the purple bacterial reaction centre to Photosystem-II, and suggest that the latter is more ancient than previously supposed. PMID- 2246902 TI - A generalized theoretical treatment of the kinetics of an enzyme-catalysed reaction in the presence of an unstable irreversible modifier. AB - A generalized theoretical treatment of the kinetics of an enzyme-catalysed reaction in the presence of an unstable irreversible inhibitor (or activator) is presented. Analytical expressions describing the time-dependence of product formation have been derived in coefficient form amenable to non-linear regression analysis for two operationally distinct types of reaction mechanism dependent on whether the reaction of the unstable modifier (X) with either or both the free enzyme (E) and enzyme-substrate complex (ES) occurs as a simple bimolecular process, or proceeds through the intermediacy of either or both adsorptive enzyme modifier (EX) and enzyme-modifier-substrate (EXS) complexes in what may be considered as an extension of the Botts-Morales general modifier mechanism for (stable) reversible enzyme inhibitors and activators. Special cases of both models are classified in an analogous way to the traditional naming of reversible enzyme modifications, and guidelines concerning tests of mechanism and determination of kinetic parameters are given. In particular, it has been shown that kinetic constants describing enzyme inactivation by an unstable site specific inhibitor forming a reversible EX complex prior to covalent modification step may be determined from a single progress curve. Kinetic analysis of the extended Botts-Morales mechanism describing irreversible enzyme inactivation has demonstrated that analytical expressions describing the time-course of product formation may be derived for a stable modifier by retaining the usual steady state assumptions regarding the fluxes around ES and EXS provided quasi equilibrium modifier binding to E and ES is assumed, but for unstable modifiers all of the binding steps must be assumed to be at quasi-equilibrium in the steady state, except under restrictive circumstances. PMID- 2246903 TI - Hypoplastic transverse arch and coarctation in neonates. Surgical reconstruction of the aortic arch: a study of sixty-six patients. AB - From Jan. 1, 1983, to Jan. 1, 1988, 66 consecutive neonates with coarctation and severe hypoplasia of the transverse arch underwent coarctation repair by resection of the coarctation and reconstruction of the aortic arch. Mean age at operation was 14 +/- 8 days, ranging from 2 to 30 days; 63% of the newborn infants were less than 2 weeks of age. The coarctation was isolated in 23%, associated with a ventricular septal defect in 39%, and associated with complex anomalies in 38%, including 16 cases of transposition of the great arteries or doublet-outlet right ventricle plus ventricular septal defect, two cases of simple transposition, two of corrected transposition plus ventricular septal defect, and five cases of "hypoplastic" left ventricle. The surgical technique comprises a wide resection of the coarctation extended to the contiguous ductal tissue followed by the reconstruction of the aortic arch in bringing the descending aorta into the concavity of the aortic arch. This technique is able to relieve the obstruction of the aortic arch provided that (1) the descending aorta is widely dissected to allow mobilization and (2) the incision of the transverse arch is extended proximal to the ostium of the left carotid artery. The operation was performed through a left thoracotomy in 62 patients and through a sternotomy in four additional neonates with transposition and ventricular septal defect who underwent a one-stage repair with aortic reconstruction, closure of the defect, and arterial switch. The overall early mortality rate (less than 30 days) was 14% (9/66; 95% confidence limits = 5% to 22%), including four deaths occurring within the first month, at a concomitant or subsequent repair of the associated anomaly. There were six late deaths, all related to the associated lesions. The overall mortality rate was 23% (15/66; 95% confidence limits = 13% to 33%). The mean follow-up was 21 +/- 10 months, ranging from 6 to 66 months. Actuarial survival rates at 5 years are 72% +/- 10% for the overall group; 87% +/- 17% for simple coarctation; 88% +/- 12% for coarctation and ventricular septal defect; and 52% +/- 18% for complex coarctation. The rate of recurrent coarctation was 12.5% (95% confidence limits = 2% to 23%), leading to five reoperations with no deaths. Freedom from reoperation was 89.5% +/- 9% at 5 years. This technique of coarctation repair offers several advantages: low operative mortality, complete relief of the left ventricular obstruction, wide resection of the ductus tissue, absence of prosthetic material, and preservation of the left subclavian artery. PMID- 2246904 TI - A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia. AB - The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy. PMID- 2246905 TI - Hemodynamics and oxygen uptake below and above aortic occlusion during crossclamping of the thoracic aorta and sodium nitroprusside infusion. AB - The effects of controlled vasodilation on blood flow and oxygen consumption above and below the aortic occlusion during crossclamping of the thoracic aorta were examined in 16 mongrel dogs anesthetized with halothane. Blood flow in the inferior vena cava was measured with an electromagnetic cannulating flow probe, and cardiac output was measured by thermodilution. The animals were divided into two groups. In the control group the thoracic aorta was crossclamped at the diaphragmatic level for 30 minutes. In the sodium nitroprusside group the aorta was also crossclamped for 30 minutes, but an infusion of sodium nitroprusside was initiated after 10 minutes of occlusion to decrease systemic blood pressure. Measurements were made before and at 10, 20, and 30 minutes after aortic crossclamping, and at 10 minutes after aortic unclamping. Crossclamping of the thoracic aorta was associated with marked decreases in blood flow and oxygen consumption in organs and tissues below the aortic occlusion in both groups. Above the occlusion, blood flow increased but oxygen uptake decreased. Sodium nitroprusside increased cardiac output and blood flow above the aortic occlusion even more than crossclamping alone while it decreased blood flow and oxygen consumption below the crossclamp. PMID- 2246906 TI - National survey of the pattern of care for carcinoma of the lung. AB - A national survey of the patterns of care for carcinoma of the lung sponsored by the Commission on Cancer of the American College of Surgeons has documented continuing changes in epidemiology, treatment, and outcome. The project consisted of a long-term study of 15,219 patients whose diagnosis was made in 1981 and a short-term study of 19,074 patients whose diagnosis was made in 1986. The male/female incidence ratios have continued to decrease and the decrease has moved into the older age groups. Although the percentage of adenocarcinoma is increasing at the expense of squamous carcinoma, the latter is still the most prevalent histologic type. The accuracy of percutaneous needle biopsy and transbronchial biopsy of lung nodules reported from this group of 941 hospitals was high and equal to that reported by single institutions. The percentage of patients having a resection did not increase from 1981 to 1986, but for smaller lesions a move was apparent toward more lung-sparing resections. Little change has occurred in the use of adjuvant radiotherapy, particularly in stage III disease, where approximately 50% of the patients received postoperative irradiation. An improvement in the overall 5-year survival when compared with Surveillance, Epidemiology, and End Results data was noted. Whether this is a true improvement in survival or is the result of selection because of an unrecognized change in the pattern of care for patients with a carcinoma of the lung is unknown. PMID- 2246907 TI - Utility of frozen-section evaluation of lymph nodes in the staging of bronchogenic carcinoma at mediastinoscopy and thoracotomy. AB - We conducted a retrospective analysis of the utility of frozen-section diagnoses in determining lymph node status at mediastinoscopy in 122 consecutive patients with bronchogenic carcinoma. Thirty-five of 122 patients had one or more lymph nodes with frozen-section evaluation positive for metastatic carcinoma. Subsequent nodal sections not in the original frozen-section study revealed metastatic carcinoma in two additional patients. The false-negative rate was 1.6%. Sensitivity was 94.6%. Predictive value of negative frozen-section evaluation results was 97.7%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section evaluation were 100%. The statuses of individual lymph nodes from these 122 patients were also evaluated. Six hundred twenty lymph nodes were sampled from the mediastinum at mediastinoscopy. Frozen-sections in 47 lymph nodes were positive. Subsequent nodal sections not in the original frozen-sections examination revealed metastatic carcinoma in four additional lymph nodes. The false-negative rate was 0.6%. Sensitivity was 92.2%. Predictive value of negative results from frozen-section evaluation was 99.3%. Because there were no false positive frozen-section results, specificity and predictive value for positive results of frozen-section examination were 100%. We conclude that frozen-section evaluation of lymph nodes at mediastinoscopy reliably indicates lymph node status, thus enabling the physician to decide whether to proceed to thoracotomy. Thus staging of the carcinoma and definitive surgery can be accomplished during a single anesthetic procedure. Combining mediastinoscopy and thoracotomy with frozen-section diagnostic control also reduces both the length and cost of hospitalization. PMID- 2246908 TI - Primary osteosarcoma of the lung. Report of two cases and review of the literature. AB - Two cases of primary osteosarcoma of the lung are presented. In one case, the radiologic, clinical, and cytologic findings led to a preoperative diagnosis of undifferentiated carcinoma of the lung. In the second case, a lung nodule was discovered during postchemotherapy follow-up in a patient with lymphoma. Fine needle aspiration in the second case showed lymphoma, and further chemotherapy was instituted; however, persistent growth of the nodule prompted a resection. Microscopic examination of the resected tumors in both cases revealed histologic features of high-grade osteosarcoma. Flow cytometric analyses of the primary tumors showed abnormal hyperdiploid deoxyribonucleic acid populations in accordance with those seen in high-grade malignant neoplasms. Immunohistochemical studies supported a mesenchymal origin for these tumors. These tumors shared clinical features with other reported cases of primary osteosarcoma of the lung such as large size at diagnosis, occurrence in older individuals, and aggressive behavior. PMID- 2246909 TI - Advances in cancer research: bench to bedside. PMID- 2246910 TI - Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences. AB - This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms. PMID- 2246911 TI - Studies of myocardial protection in the immature heart. II. Evidence for importance of amino acid metabolism in tolerance to ischemia. AB - This study tests the importance of amino acid transamination in determining the tolerance of immature hearts to ischemic damage. Amino acid transamination was inhibited metabolically by pretreatment with aminooxyacetic acid. The aminooxyacetic acid dose and duration were determined by incubating in vitro tissue homogenate and showing that an 8 mmol/L AOA dose for 5 minutes blocked 90% of alanine aminotransferase and aspartate aminotransferase activity. Control studies in nonischemic hearts showed that coronary perfusion with aminooxyacetic acid for 5 minutes did not impair myocardial performance. In contrast, pretreatment of immature puppies with aminooxyacetic acid severely impaired recovery after 45 minutes of normothermic global ischemia (30% versus 85% recovery in untreated hearts, p less than 0.05). Biochemical analyses of hearts undergoing ischemia showed aminooxyacetic acid to limit lactate production, impair glutamate utilization, prevent alanine production, and limit succinate accumulation (p less than 0.05). These data suggest that amino acid transamination is an important adaptive process in the immature heart that improves its resistance to ischemic damage. PMID- 2246912 TI - Warm induction blood cardioplegia in the infant. A technique to avoid rapid cooling myocardial contracture. AB - The use of profound hypothermia and total circulatory arrest for repair of heart defects in neonates usually involves a period of systemic and myocardial bypass cooling. Rapid cooling of muscle (skeletal, smooth, and myocardial) can result in contracture through elevation of cytosolic calcium levels. The increased myocardial tone caused by cooling might render the heart more vulnerable to a subsequent period of cardioplegic ischemic arrest. Infants may be more susceptible to contracture because their small body mass allows more rapid myocardial temperature change when prearrest bypass cooling is used. The influence of avoiding rapid myocardial cooling before induced cardioplegic arrest was analyzed in a group of infants weighing less than 6 kg at the time of open cardiac operation. Myocardial ischemic arrest by warm (37 degrees C) induction blood cardioplegia was used in 57 infants and compared with results in 440 infants treated with standard blood cardioplegia. Multivariate logistic regression analysis revealed that patient diagnosis, weight, and age at operation were significant risk factors for operative mortality. The use of warm induction blood cardioplegia had a strongly positive independent effect on survival (p = 0.0003) for any patient weight, age, or diagnostic group. We recommend the avoidance of rapid myocardial cooling on bypass in all patients before induction of cardioplegic ischemic arrest. PMID- 2246913 TI - Cardioplegia for the immature myocardium. A comparative study in the neonatal rabbit. AB - This study examined the effect of hypothermia (15 degrees C) alone or combined with various cardioplegic solutions on functional recovery of the neonatal heart after 120 minutes of global ischemia in an isolated working rabbit heart model. Control hearts were preserved with hypothermia alone, and groups 1 to 6 were given different hyperkalemic crystalloid cardioplegic solutions. Each cardioplegic solution differed in Na+ and Ca++ content. Aortic flow, coronary flow, cardiac output, heart rate, peak systolic pressure, and stroke work were measured before ischemia and after 35 and 45 minutes of reperfusion. There were no statistical differences in hemodynamic recovery in the six groups in which cardioplegia was used. However, hearts preserved with multidose hyperkalemic cardioplegia showed significantly better recovery of cardiac output (86% versus 75%; p less than 0.05), coronary flow (88% versus 72%; p less than 0.05), and stroke work (86% versus 75%; p less than 0.05) than those preserved with hypothermia alone. These results suggest that hypothermic hyperkalemic cardioplegia improves preservation of the neonatal rabbit heart but that variations in Ca++ and Na+ content appear not to provide further myocardial protection. PMID- 2246914 TI - Long-term cardiopulmonary bypass by peripheral cannulation in a model of total heart failure. The decompression of the left heart through a percutaneous helical spring positioned within the lumen of the tricuspid and pulmonary artery valves. AB - We performed long-term closed-chest cardiopulmonary bypass in an animal model of total heart failure (induced ventricular fibrillation). The extracorporeal system included a venous reservoir, a roller pump, a membrane lung, and a blood pulsator system. We cannulated the right external jugular vein for venous drainage and the right subclavian artery for arterial return. To decompress the left heart we passed by percutaneous cannulation a special helical spring mounted on a Swan Ganz catheter (Baxter Edwards Divisions, Irvine, Calif.) and positioned it to rest within the pulmonary artery and tricuspid valves, which rendered them partly incompetent. After induced ventricular fibrillation, blood flow was raised to keep the central venous pressure at baseline values. The lungs were ventilated with 5% carbon dioxide in room air. During bypass, mean pulmonary artery pressure was 10.0 +/- 1.7 mm Hg, mean wedge pressure 11.9 +/- 1.8 mm Hg, and mean blood pressure 95.2 +/- 5.6 mm Hg. After 2 days (four animals) and 3 days (two animals) the hearts were defibrillated. There was immediate ejection from both sides of the heart. All sheep were weaned from bypass within 29 +/- 11 minutes and their lungs were ventilated with room air within 42 +/- 34 minutes. At autopsy hearts and lungs grossly appeared normal. We conclude that the percutaneous helical spring resting within right heart valves provided excellent decompression throughout the study, with full recovery of heart and lung function on defibrillation. PMID- 2246915 TI - Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. AB - Supraventricular tachyarrhythmias are reported in up to 40% of patients early after coronary artery bypass graft operations. In a randomized study, we compared the efficacy and safety of the class III antiarrhythmic beta-blocking drug sotalol versus propranolol at low and high doses in the prevention of supraventricular tachyarrhythmias in 429 consecutive patients after coronary artery bypass graft operations. Patients with severely depressed left ventricular function and other contraindications for beta-blockers were excluded. From the fourth hour up to the sixth day after coronary artery bypass, 74 patients received low-dose sotalol (40 mg every 8 hours), 66 patients low-dose propranolol (10 mg every 6 hours), 133 patients high-dose sotalol (80 mg every 8 hours), and 156 patients high-dose propranolol (20 mg every 6 hours). Baseline characteristics were comparable in all groups. Supraventricular tachyarrhythmia was observed in 10 of 72 (13.9%) who received low-dose sotalol, 12 of 64 (18.8%) who received low-dose propranolol, 13 of 119 (10.9%) who received high-dose sotalol, and 19 of 139 (13.7%) who received high-dose propranolol (not significant). Drug-related adverse effects necessitating discontinuation of the drug occurred in four receiving low doses (2.9%) and in 31 receiving high doses (10.7%) (p less than 0.02). In conclusion, no medication was found to be superior, although supraventricular tachyarrhythmias tended to be less prevalent in patients treated with sotalol than in those treated with propranolol. Moreover, significantly fewer adverse effects were noted in both low-dose groups. Therefore, low-dose beta-blocking treatment, especially low-dose sotalol, seems preferable. PMID- 2246916 TI - Neonatal aortic stenosis. The balloon deflated? PMID- 2246917 TI - Delayed sternal closure in neonate. PMID- 2246918 TI - Massive arterial air embolism during cardiac operation: successful treatment in a hyperbaric chamber under 3 ATA. PMID- 2246919 TI - Transatrial balloon technique for activation mapping during operations for recurrent ventricular tachycardia. PMID- 2246920 TI - Quantitative assessment of mechanical energy in pulsatile blood flow during cardiopulmonary bypass. PMID- 2246921 TI - Purulent pericarditis resulting from blunt chest trauma. PMID- 2246922 TI - Sequentially paced heterotopic heart transplant. PMID- 2246923 TI - Spectral analysis and acoustic transmission of mitral and aortic valve closure sounds in dogs. Part 1. Modelling the heart/thorax acoustic system. AB - A system model based on the simultaneous recording and analysis of the intracardiac and thoracic phonocardiograms to estimate the time-varying properties of the heart/thorax acoustic system of the dog is described. The presence of instrumental noise in the recording of intracardiac phonocardiograms is characterised, and it is demonstrated that its effect on the estimate of the transfer and coherence functions of the system can be quantified and corrected. Application of the model to study the spectral characteristics and the acoustic transmission properties of the mitral component M1 of the first heart sound and of the aortic component A2 of the second heart sound in the dog shows that the heart/thorax acoustic system acts like a bandpass filter having a higher attenuation for A2 than for M1. Between 20 and 100 Hz, the mean attenuation of M1 is 30 dB while that of A2 is 46 dB. Above 100 Hz, the attenuation slope is -12 dB per octave for M1 and -6 dB per octave for A2. PMID- 2246924 TI - Spectral analysis and acoustic transmission of mitral and aortic valve closure sounds in dogs. Part 2. Effects of neuromuscular blockade, sternotomy and pacemaker control, and a two-week recovery period. AB - The paper describes the effects of neuromuscular blockade, sternotomy and atrio ventricular pacing, and a two-week recovery period on the spectra and acoustic transmission of mitral M1 and aortic A2 sound components in dogs. Results indicate that neuromuscular blockade does not affect the attenuation properties of the heart/thorax acoustic system even if it modifies the intensity of M1 and the phase of the transfer function. The immediate effect of sternotomy and cardiac pacing is an important increase in the attenuation of the heart/thorax acoustic system. This increased attenuation is different for both sounds (20 dB for M1 and 11 dB for A2) and disappears after a two-week recovery period. However, the resulting controlled dog model shows slightly different acoustic characteristics than those of the normal animal model. PMID- 2246925 TI - Complete foetal ECG morphology recording by synchronised adaptive filtration. AB - Present noninvasively measured indices of foetal stress are indirect and not sufficient. Foetal electrocardiography (FECG) is a potential noninvasive measurement of the foetus wellbeing which has been little utilised because of the difficulties of measuring it. The development of time-sequenced adaptive filters which are synchronised to the QRS complex by the use of Doppler echocardiography allowed the recording of relatively noise-free FECG. The paper describes the use of this technique for obtaining the complete complex of the FECG. Several sets of time-sequenced adaptive filters are combined to allow a multilead abdominal recording to produce a measurement system which rejects maternal ECG and enhances the FECG. Five subjects have been analysed, and their FECGs have been accurately reproduced with minimal changes of the filters' parameters. PMID- 2246926 TI - Estimation of arterial compliance in aortic regurgitation: three methods evaluated in pigs. AB - Three methods for measuring arterial compliance when aortic regurgitation is present are examined. The first two methods are based on a Windkessel model composed of two elements, compliance C and resistance R. Arterial compliance was estimated from diastolic pressure waveforms and diastolic regurgitant flow for one method, and from systolic aortic pressure waveforms and systolic flow for the other method. The third method was based on a three-element Windkessel model, composed of characteristic resistance r, compliance C and resistance R. In this method arterial compliance was calculated by adjusting the model to the modulus and phase of the first harmonic term of the aortic input impedance. The three methods were compared and validated in six anaesthetised pigs over a broad range of aortic pressures. The three methods were found to give quantitatively similar estimates of arterial compliance at mean aortic pressures above 60 mm Hg. Below 60 mm Hg, estimates of arterial compliance varied widely, probably because of poor validity of the Windkessel models in the low pressure range. PMID- 2246927 TI - Quantification of aortic regurgitation by Doppler echocardiography: a new method evaluated in pigs. AB - We have developed a method to quantify aortic regurgitant orifice and volume, based on measurements of the velocity of the regurgitant jet, aortic systolic flow, the systolic and diastolic arterial pressures, a Windkessel arterial model, and a parameter estimation technique. In six pigs we produced aortic regurgitant flows between 2.1 and 17.8 ml per beat, i.e. regurgitant fractions from 0.06 to 0.58. Pulmonary and aortic flows were measured with electromagnetic flow probes, aortic pressure was measured invasively, and the regurgitant jet velocity was obtained with continuous-wave Doppler. The parameter estimation procedure was based on the Kalman filter principle, resulting primarily in an estimate of the regurgitant orifice area. The area was multiplied by the velocity integral of the regurgitant jet to estimate regurgitant volume. A strong correlation was found between the regurgitant volumes obtained by parameter estimation and the electromagnetic flow measurement. These results from our study in pigs suggest that it may be possible to quantify regurgitant orifice and volume in patients completely noninvasively from Doppler and blood pressure measurements. PMID- 2246929 TI - Effect of intracellular anisotropy on electrical source determination in a muscle fibre. AB - Expressions are available for describing, quantitatively, the source associated with an action potential propagating along an excitable fibre. For a nerve fibre one such expression defines an equivalent volume dipole density function tau(x) = -delta/delta x (sigma i phi i (x) - sigma e phi e (x)) ax (where x is the axial co-ordinate, i is the intracellular and e the extracellular region, sigma i and sigma e are isotropic conductivities, phi the potential at the membrane, while axial symmetry is assumed), and this source fills the intracellular region. This source, as distinct from transmembrane current formulations, lies in a uniform, isotropic, extracellular, medium. Consequently, for a fibre bundle a simple superposition of sources, all lying in a uniform, isotropic, extracellular space, can be accomplished. However, for muscle fibres the presence of non-conducting myofibrils causes the intracellular space to be anisotropic. The paper describes the modification in the aforementioned expressions for the case of longitudinal and transverse propagation and extrapolation to an arbitrary angle of propagation. The resultant source continues to be expressed relative to a uniform, isotropic, extracellular medium. PMID- 2246928 TI - Development of methods to analyse transcranial Doppler ultrasound signals recorded in microgravity. AB - During space flights, several clinical syndromes may be the result of changes in cerebral circulation. The purpose of the paper is to describe the development and initial evaluation of a system for recording, processing and displaying transcranial Doppler ultrasound (TCD) waveforms from the middle cerebral artery (MCA) in microgravity. Volunteers were repeatedly subjected to 15-20 s intervals of microgravity ('near zero gravity') during flights on the KC-135 military aircraft. Continuous TCD recordings from the MCA were stored on magnetic tape. The paper describes the system that was developed to digitise the Doppler ultrasound data and markers that corresponded to the various levels of microgravity, obtain the maximum and mean Doppler waveforms, identify the waveforms and quantify them. The results demonstrate the feasibility of making TCD recordings in a microgravity environment and illustrate excellent performance of the system and its ease of operation. Quantitative waveform analysis of the recordings from the first subject studied in the supine position showed statistically significant changes in MCA velocity waveforms during microgravity. PMID- 2246930 TI - Development of an eye-movement analyser possessing functions for wireless transmission and autocalibration. AB - An eye pointer was developed as a new line-of-sight displacement analyser. It analyses an observer's eye movements and superimposes their line of vision on a TV image which is the same as their view. A newly developed miniature colour field camera and very compact eye-movement sensors are attached to a translucent reinforced plastic goggle affording a wide view and excellent safety. A small case is provided for the eye-movement detecting circuit and the camera controller unit etc. Its weight is only 1.2 kg and one can easily participate in sports activities while wearing it. Eye-movement data are transmitted with the VHF video signal. The receiver, which analyses the eye movements and processes the TV image, is also compact and easy to carry. The calibration is automatic and completed within 1 min with a high degree of accuracy. By showing the tennis player's line of vision as an example, we were able to obtain good results with application in broadcasting programmes. PMID- 2246931 TI - Mathematical model to analyse urea synthesis following alanine infusion in control subjects and in patients with liver cirrhosis. AB - A three-compartment model was used to analyse the urea response to an alanine infusion in control subjects and patients with liver cirrhosis. Discriminant analysis showed a good separation between model coefficients of the two groups. A single parameter was derived, able to quantify the liver functional capacity. The method provides a useful diagnostic tool in patients with liver disease. PMID- 2246932 TI - Computer-controlled wheelchair ergometer. AB - A new wheelchair ergometer has been designed in which a combination of realistic simulation of wheelchair propulsion--with adjustable parameters for rolling resistance, air drag, wind speed and slope--and force measurement has been realised. The static solution enables the measurement of physiological and kinesiological parameters. All data from force transducers in seat and backrest, torque transducers in the wheels and force transducers in the wheelframes as well as the acquired speed are sampled in a data-acquisition system. An offline curve processor allows the acquired data to be processed with standard or custom programmed routines. Preliminary results have been added and are discussed. PMID- 2246933 TI - Multimicroprocessor system for online monitoring in a CCU. AB - A real-time monitoring system for physiological signals, developed for patients in coronary care units (CCUs), is described. This system monitors the signals that have the greatest clinical value in a CCU environment (ECG and cardiovascular pressures), taking charge of detecting dangerous situations and of extracting information significant to the correct monitoring of the patient. The information it extracts, mainly from the ECG, is presented to the user in an ergonomic way using written reports and graphs which collect and compile the information, facilitating its interpretation. Some utilities have been developed to allow the user to modify certain monitoring conditions as well as to correct results derived from them, thereby improving the reliability of the monitoring process. The system uses a multimicroprocessor architecture (imposed by the need to perform a large number of tasks in real time) with a block based on the VME bus, charged with acquiring and processing the monitored signals, and an IBM compatible PC/XT which is used as a system user interface and a massive storage device in which the information resulting from the monitoring of signals is stored. PMID- 2246934 TI - Information system for biomedical equipment management in a wide-area environment. AB - An information system used in managing the inventory of equipment at the local health units (LHUs) of the Emilia Romagna region is presented. The system aims at efficient management of information on medical equipment and at supporting regional administrators in financial planning. The system uses 'classification files' and 'working files'. The classification files can be either defined at national (classification of producers, models and equipment types) or local (classification of suppliers and hospital departments) level. The working files are used to store all information necessary for the inventory of equipment in the local health unit (equipment inventory file) and results of automatic annual economic computations (residual values and amortisation quota file). Starting from data stored in the above-mentioned files the system can perform several procedures, such as control on data entry, economic computations and report printings. The main aspects of these operations are described in detail. Finally, some information on biomedical equipment of one of the largest local health units of the Emilia Romagna region, obtained from elaboration of system data, is shown and discussed. PMID- 2246935 TI - Kinematic-based technique for event time determination during gait. AB - A kinematic-based technique for the estimation of the times at which gait events occur is presented. A kinematic-based model (KM) is defined by the trajectory of a point, which has an anatomically fixed location on the subject's body, about a time at which a measurement system defined gait event takes place. The times at which subsequent occurrences of the gait event takes place are determined by identifying the kinematic pattern that best fits the previously defined KM. The results of an experiment that used the gait patterns of a normal and a pathological walker indicate that the accuracy of the algorithm is limited by the kinematic data sampling interval and that optimal kinematic predictors of gait event times occur within the primary (sagittal) plane of motion. The technique is intended to obviate the need for multiple force plates, instrumented floors and instruments which are worn by the subject for the purpose of determining the times at which gait events occur. PMID- 2246936 TI - Mechanical impedance of the canine diaphragm. Part 1. Experimental system and measurements. AB - A technique which does not require the measurement of strain has been developed for the investigation of the incremental dynamic properties of soft tissue sheets. Radially prestressed and circularly clamped canine diaphragm samples were exposed to small-amplitude pseudorandom pressure variations. From the measurement of these pressure variations and the volume flow caused by the vibration of the membrane the incremental mechanical impedance spectrum was computed in the 0.25-5 Hz frequency range at three different levels of initial stress. The diaphragm tissue was found to be basically elastic. However, the small viscous component showed a sharp negative frequency dependence between 0.25 and 2 Hz. The quasistatic elastances of the samples were in good agreement with the elastance values derived from the impedance data. The relationship between the elastance and the initial stress was close to linear. It was concluded that the method is applicable to the study of the incremental dynamic properties of planar soft tissue samples. PMID- 2246937 TI - Mechanical impedance of the canine diaphragm. Part 2. Theoretical model and parameter estimation. AB - In the paper the equation of motion of the small amplitude transverse forced vibration of a radially prestressed and circularly clamped thin membrane has been developed. The material of the membrane is considered to be homogeneous, isotropic, incompressible and viscoelastic. From the analytical solution of this equation the incremental mechanical impedance of the membrane was derived as a function of frequency, geometrical parameters and incremental viscoelastic coefficients of the material. The parameters of the model were fitted to experimental impedance data using a global optimisation procedure to obtain the incremental viscoelastic moduli of the canine diaphragm. The estimated quasi static behaviour of the model is shown to be consistent with the results of experimental quasi-static measurements. It is concluded that the incremental viscoelastic moduli of a soft tissue and the stress dependence of these material coefficients can be determined by fitting the parameters of the model to the impedance data of that particular tissue. PMID- 2246938 TI - EMG power spectrum as a measure of muscular fatigue at different levels of contraction. AB - The shift in the power spectrum resulting from a 5-7 min fatigue-inducing effort followed by a 1-2 min recovery period of two elbow flexors, the biceps brachii (BB) and the brachio-radialis (BR), was assessed using two variables, the mean frequency Fm and the median or central frequency Fmd. These two variables were calculated in pre- and post-fatigue conditions and following a brief recovery, at four levels, namely 20, 40, 60 and 80 per cent of maximum voluntary contraction (MVC). These were taken from a ramped isometric effort that is from 0 to 100 per cent MVC. The EMG activity of the two flexors was recorded with bipolar surface electrodes from a group of ten volunteers. Following muscle fatigue, induced with a maintained 60 per cent MVC isometric contraction, a statistically significant (p less than 0.05) shift towards the lower frequencies was observed for both Fm and Fmd for both muscles. Following a brief recovery, a shift towards the pre fatigue higher frequencies was statistically significant (p less than 0.05). These two synergists responded to muscle fatigue and recovery similarly, as they both demonstrated parallel shifts in power spectrum. The power spectrum is consequently a reliable measure of muscular fatigue. It is also complementary to the net articular moment results. PMID- 2246939 TI - Slope of the EMG/moment relationship as a measure of muscular fatigue: a validation study. PMID- 2246940 TI - ECG noise on cardiopulmonary bypass. PMID- 2246941 TI - Topographical EEG mapping by means of the structure function. PMID- 2246942 TI - Quality of life bibliography and indexes. PMID- 2246943 TI - A general model of sexually transmitted disease epidemiology and its implications for control. AB - Achieving control of STDs may be possible by integrating the activities discussed previously with further research to provide additional empiric data on sex behavior, to develop innovative strategies to access and communicate with those most at risk of STD (i.e., core-group members), and to foster biologic study of STD pathogens with the goal of vaccine development. New strategies to identify core-group members aside from the currently used STD-repeater status would be of immense help in targeting educational efforts, laboratory screening, and vaccines. Achieving more complete control of STDs may be possible if recent advances in our understanding of their epidemiology and transmission dynamics can be translated into effective new interventional strategies. PMID- 2246944 TI - Sexually transmitted diseases. PMID- 2246945 TI - Chlamydial infections. AB - Chlamydia trachomatis is a unique intracellular parasite that causes a number of common sexually transmitted disease syndromes, including nongonococcal urethritis in both men and women, epididymitis in men, and pelvic inflammatory disease in women. Infants exposed at delivery are at risk for the development of conjunctivitis and pneumonia. There is strong evidence that Chlamydia is a cause of obstructive infertility and ectopic pregnancy in women. It appears that these complications result from the chronic inflammatory response and secondary scarring that are elicited by long-term asymptomatic or nearly asymptomatic fallopian tube infections. Because treatment with tetracycline, doxycycline, or erythromycin is simple, effective, and inexpensive, major efforts should be put into identifying asymptomatic young women through screening of the subpopulations at highest risk. These include sexually active adolescent women and older women who are not monogamous. Blacks are at higher risk than other ethnic groups for infection. The cost of diagnosing chlamydial infection has decreased with the introduction of new nonculture diagnostic tests. This should increase the availability of testing for screening purposes. It is critical to remember that male sex partners of infected women must be treated; otherwise all efforts to prevent long-term complications by identifying and treating asymptomatic women are doomed to failure. PMID- 2246946 TI - Syphilis in adults. AB - This article reviews the clinical manifestations of syphilis, diagnostic tests that might help to diagnose accurately the disease, and current recommendations for therapy. The association of syphilis and human immunodeficiency virus infection raises additional questions related to transmission, diagnosis, and therapy of both diseases. PMID- 2246948 TI - Genital herpes simplex virus infections. AB - There has been a dramatic increase in patient visits to physicians for evaluation and treatment of genital herpes infections. This has resulted in part from an increase in genital herpes infections, particularly severe, first-episode genital herpes infections in adults without prior HSV-1 infection. Virus culture remains the most sensitive and specific method for diagnosis, and use of viral cultures is encouraged. Type-specific antibody tests have been employed in studies documenting the role of asymptomatic shedding of HSV in transmission of genital infections, the role of genital HSV in transmission of HIV, the predominance of asymptomatic and unrecognized infections in those infected with HSV-2, and the presence of past asymptomatic or unrecognized acquisition of HSV-2 in 25% of persons presenting with first-episode genital herpes. Unfortunately, commercially available serologic tests do not reliably differentiate between antibody to HSV-1 and HSV-2. Recent studies suggest that the annual risk of transmission from a sexual partner with genital herpes is about 10% in heterosexual couples. Currently, promotion of "safe sex" is the only available approach for prevention of transmission. However, ongoing research is focused on the development of an effective vaccine. Acyclovir should be used routinely in persons with first episode genital herpes, but careful evaluation is needed in persons with recurrent genital herpes to determine whether episodic or suppressive treatment is indicated. Acyclovir should also be used routinely for episodic or suppressive treatment of HSV infections in persons with AIDS. Additional antiviral agents are needed for more effective suppressive therapy and for treatment of ACV-resistant HSV infections in the immunocompromised host. PMID- 2246947 TI - Chancroid and the role of genital ulcer disease in the spread of human retroviruses. AB - Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease. PMID- 2246949 TI - The "nuisance" sexually transmitted diseases: molluscum contagiosum, scabies, and crab lice. AB - Although molluscum contagiosum, scabies, and infestation by crab lice do not carry the requirements of partner notification or other long-term consequences, they are among the most commonly reported sexually transmitted disease. Molluscum contagiosum is a benign viral infection of the skin epidermal layer, most often transmitted by intimate skin-to-skin contact. The lesions often resolve spontaneously over time, but patient discomfort or social reasons may require destructive removal of the lesions. Scabies is caused by the Sarcoptes scabiei mite. The victims continually itch, especially at night, and often seek over-the counter topical remedies before seeing a clinician. Once a correct diagnosis is made, successful resolution of this disease and its itching can be achieved. Head and pubic lice account for most of the more than three million cases of louse infestation treated in the United States each year. Symptoms of infestation generally include itching that leads to scratching, erythema, irritation, and inflammation. A careful diagnosis followed by disinfection, symptomatic treatment, and psychologic support should result in a complete cure with no long term effects. PMID- 2246950 TI - Common nonvenereal genital lesions. AB - There are a wide variety of local and systemic skin diseases that produce lesions in the genitoanal region. These lesions may resemble those produced by sexually transmitted microorganisms. The purpose of this article is to make physicians aware of the common skin diseases that produce lesions on the genitalia to avoid the inappropriate diagnosis of a sexually transmitted disease. PMID- 2246951 TI - The emergence of hepatitis B as a sexually transmitted disease. AB - In the United States, approximately 300,000 cases of hepatitis B virus infection occur annually, and heterosexual activity is one of the most commonly reported risk factors for acquiring disease. Until the number of infections transmitted through heterosexual contact can be reduced through hepatitis B vaccination, there is little chance of controlling this infection. PMID- 2246952 TI - Approach to men with urethritis and urologic complications of sexually transmitted diseases. AB - The most important causes of urethritis, and epididymitis in younger men, are C. trachomatis and N. gonorrhoeae. Management of these syndromes requires a thorough sexual history, genital examination, evaluation for objective and laboratory evidence of infection, antimicrobial therapy directed toward the major etiologies, and evaluation and treatment of sexual partners. Treatment of N. gonorrhoeae requires use of a single-dose regimen active against this organism, plus a 7- to 10-day tetracycline regime active against C. trachomatis and nongonococcal urethritis. With recommended regimens, microbiologic failure is infrequent in compliant patients. Recurrent urethritis is frequent, however. The management of patients with persistent or recurrent symptoms requires careful reevaluation of the patient, documentation of urethritis, and re-treatment with antimicrobials if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leukocytes in urethral secretions. Additional treatment beyond this point usually is not indicated, even though a proportion of men will remain symptomatic and some of these will have increased numbers of polymorphonuclear leukocytes in urethral secretions. The most important causes of prostatitis, and epididymitis in older men or men with urethral structural abnormalities, are classical urinary tract pathogens rather than sexually transmitted pathogens. Management of these infections includes documentation of the infection and treatment directed toward the specific pathogen. Men with symptoms of "prostatitis" must be evaluated using both urine and prostatic secretions to document infection and inflammation. The majority of men with such symptoms do not have an infection that can be documented. These men respond poorly to medications. Men with documented chronic bacterial prostatitis require long courses of antimicrobials to effect cure. In some cases, however, the disease is intractable, and chronic suppression with antimicrobials may be necessary. PMID- 2246953 TI - Approach to the patient with genital ulcer disease. AB - The three major diseases characterized by genital ulcers--genital herpes, syphilis, and chancroid--are common, with genital herpes being most common in industrialized countries and chancroid being most common in developing countries. One fourth to one half of patients with genital ulcers have no diagnosed cause for their illness despite diagnostic efforts. The bulk of these cases is probably constituted by one of the three diseases for which diagnostic tests are falsely negative. There is accumulating evidence that genital ulcers facilitate the transmission of human immunodeficiency virus (HIV), and they may also be markers of high-risk behavior for acquisition of HIV. Appropriate therapy of patients with genital ulcers (as well as their sexual partners) depends on accurate diagnosis. Patients with genital ulcers, particularly those with syphilis or chancroid, should be encouraged to undergo testing for HIV infection. PMID- 2246955 TI - Pelvic inflammatory disease. AB - The costs of PID to both individuals and society are enormous. Although primary prevention of PID through control of lower genital tract infections is the most effective prevention strategy, early diagnosis and treatment of acute PID may minimize some of its serious sequelae. Although laparoscopy is helpful for establishing the diagnosis of salpingitis, other less invasive tests along with selected clinical criteria may also be useful. Treatment of PID, which is empiric and broad spectrum, is oriented toward polymicrobial PID. Whenever possible, women with PID should be hospitalized for parenteral therapy. The 1989 CDC STD treatment guidelines recommend two regimens for inpatient parenteral therapy: clindamycin/gentamicin and cefoxitin, or equivalent cephalosporin/doxycycline. Outpatient management of PID should be monitored closely; the CDC-recommended regimen includes use of intramuscular cephalosporins and oral doxycycline. Oral penicillins are no longer recommended. PMID- 2246954 TI - Vaginal infections in adult women. AB - Often trivialized by the medical profession, vaginitis in adult women is not only extremely common but is the source of considerable distress and often results in marked suffering. Epidemiologic studies described in this article indicate the high prevalence of vaginitis and the large number of causes. Although the majority of infections in women are due to bacterial vaginosis, VVC, and trichomoniasis, it is clear that many other causes exist, and we have yet to discover the etiology of many clinical syndromes. Considerable progress has been made in understanding the pathogenesis of the three common vaginitides. Although excellent progress has been made by the pharmaceutical industry in providing new drugs for vaginitis, any further progress will require a better understanding of etiology and pathogenesis. Vaginitis causes major symptoms and is more than a nuisance problem. Clinicians owe it to their patients to attempt to make an accurate diagnosis and not to rely on empiric therapy. PMID- 2246956 TI - Sexually transmitted arthritis syndromes. AB - Sexually transmitted infections may provoke a wide variety of rheumatic lesions. Disseminated N. gonorrhoeae infection leads to septic arthritis, which may be rapidly destructive but which responds promptly to appropriate antibiotic therapy. In contrast, both gonococcal and nongonococcal infections may lead to aseptic "reactive" arthritis or Reiter's syndrome. Inheritance of HLA B27 confers a relative risk of 30 to 50 times for the development of this condition. The demonstration of C. trachomatis antigen in joint material from a minority of patients suggests that direct interaction between microbial components and class I HLA antigens in the joint may be central to the pathogenesis of this disease. Arthralgia and arthritis occur in up to 50% of individuals in the prodrome of hepatitis B infection. Joint symptoms may be accompanied by urticarial or cutaneous vasculitic lesions, especially on the legs; both features resolve with the onset of jaundice. Hepatitis B infection is also a major cause of necrotizing vasculitis, which may or may not be associated with overt hepatitis. Seronegative arthritis, including Reiter's syndrome, psoriatic arthritis, and undifferentiated arthritis, a Sjogren's-like syndrome, vasculitis, and myopathies have been described in association with HIV infection. It is clear that synovitis occurs in those patients despite the fact that HIV is present in immune cells within the joint during inflammatory arthritis and that both antigen presentation and lymphocyte responsiveness within the joint are impaired. Nevertheless, synovitis may occur in the presence of marked CD4-positive lymphocyte depletion. Rheumatic syndromes, including arthralgia, inflammatory arthritis, and neuropathic arthritis, may occur during any stage of congenital or acquired syphilis. Syphilitic synovitis responds well to antibiotic therapy, but neuropathic lesions cannot be treated effectively. Septic arthritis has rarely been described as a complication of disseminated Mycoplasma or Urea-plasma infections, and joint lesions sometimes associated with erythema nodosum have also been reported in lymphogranuloma venereum and granuloma inguinale. PMID- 2246957 TI - Sexually transmitted causes of gastrointestinal symptoms in homosexual men. AB - The possible etiologic agents that may cause gastrointestinal complaints in homosexually active men are multiple, and their diagnosis is complex. This article presents a logical approach to the work-up and diagnosis of gastrointestinal complaints in homosexually active men and to discuss their treatment and disease intervention. PMID- 2246958 TI - The interrelationship between human immunodeficiency virus infection and other sexually transmitted diseases. AB - The epidemiology of HIV infection in the United States is changing, with a dramatic reduction in the incidence of new HIV infection in homosexual men over the past decade because of altered sexual practices. In contrast, heterosexual transmission of HIV is increasing and is disproportionately occurring in inner city racial minorities in association with drug use, populations that are currently experiencing epidemics of previously controlled STDs. Sexually transmitted diseases, especially genital ulcerative diseases and perhaps C. trachomatis and T. vaginalis, facilitate sexual transmission of HIV. In addition, HIV infection itself appears to increase the severity of certain STDs once they are acquired. The control of STDs, particularly in those populations that are at high risk for HIV infection, should be of high priority and should be an integral component of AIDS control programs. PMID- 2246959 TI - The effect of a time delay on the characteristics of the canine glucoregulatory system. AB - In order to elucidate the effect of a relative time delay on glucose regulation, we performed experiments with differently timed infusions of insulin and glucose in a canine model. When portal insulin infusion (0.03 U/kg over 5 minutes) preceded portal glucose infusion (0.05 g/kg over 5 minutes) by 1 minute, glycemia increased to a maximum value of 104 +/- 4 mg/dL at 6 minutes, whereas insulinemia peaked at 3 minutes at a level of 130 +/- 4 microU/mL (baseline, 21 +/- 7 microU/mL). C-peptide levels increased from 200 +/- 50 to 270 +/- 30 pmol/L. Glycemia then decreased to a minimum level of 61 +/- 4 mg/dL, significantly lower (P less than .02) than the corresponding values in control experiments when insulin was infused alone. With a reversed timing sequence of infusions with glucose infusion preceding insulin infusion by 1 minute, glycemia increased similarly, but decreased to a minimum level of only 84 +/- 4 mg/dL, which was significantly higher (P less than .01) than in the above experiment. Insulinemia peaked similarly at 126 +/- 7 microU/mL, and C-peptide increased from 210 +/- 50 to 280 +/- 50 pmol/L. These experiments demonstrated an unexpected effect: adding glucose to an insulin infusion almost doubled the biological activity of the exogenous insulin as measured by its hypoglycemic action. They also indicated that small perturbations of glycemia and insulinemia in the portal circulation have a profound effect on metabolism, and that even short relative time delays in elevating either insulinemia or glycemia can cause significantly different metabolic outcomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246960 TI - The mesophase of parenteral fat emulsion is both substrate and inhibitor of lipoprotein lipase and hepatic lipase. AB - Six 10% and 20% parenteral fat emulsions were separated by centrifugation into two fractions: (1) a supernatant containing the bulk of triacylglycerols (Tg) as fat particles stabilized by phospholipids (PL); and (2) an infranatant, called mesophase, consisting essentially of PL (one third of the original PL in the 10% formula, one sixth in the 20% formula, in the case of emulsions containing 12 g PL.L-1) and small amounts of Tg and free sterols, probably in the form of liposomes. The lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the Tg-rich lipoprotein clearance, hydrolyze both types of particles, although Tg-fat particles are their preferred substrate. Inactivated serum (providing apo C-II) is needed to ensure the maximum LPL hydrolysis rate of both types of particles. It partially inhibits the HL activity on the mesophase. Substrate of the lipolytic enzymes, the mesophase, is also an inhibitor of their activity, the inhibition being directly proportional to the amount of PL contained in the mesophase. This inhibition is of uncompetitive type. For LPL, it seems that the mesophase acts on a site distinct from that of the apo C-II binding site. These results partly explain the low PL clearance after a fat emulsion infusion. But in particular, they help to explain the lower clearance of a 10% emulsion (larger PL excess) compared with a 20% emulsion (with the same amount of Tg, but less PL excess). PMID- 2246961 TI - The effects of short-term carbohydrate overfeeding and prior exercise on resting metabolic rate and diet-induced thermogenesis. AB - In 10 young, normal-weight subjects, the effects were investigated of carbohydrate overfeeding and prior glycogen-depleting exercise on resting metabolic rate (RMR) and diet-induced thermogenesis (DIT). Subjects were kept on controlled diets in a crossover design for two periods of 8 days, with a 1-week interval in between. During the last 4 days of each period, additional carbohydrates were added to the subjects' diet. The carbohydrate overfeeding started at 15% in excess of the energy requirements on day 1 and increased to 60% on day 4. At the beginning and the end of the carbohydrate overfeeding periods, RMR and DIT were measured, respectively, for 1 and 3.5 hours using a ventilated hood system. In one of the 8-day periods, on evenings before the energy exchange measurements, subjects performed a maximum work capacity test on a cycle ergometer, and then cycled for a total of approximately 80 minutes at fixed percentages of their maximum work capacity. Carbohydrate overfeeding did not affect RMR, but increased DIT significantly, on average by 39%. Glycogen depleting exercise the day before increased RMR significantly by, on average, 9% and increased DIT (P = .08), on average, by 23%. The impact of exercise on RMR was less when carbohydrate overfeeding was administered, but there was no significant interaction effect of carbohydrate overfeeding and exercise on RMR or DIT. It is concluded that both prior glycogen-depleting exercise and an antecedent diet high in carbohydrates may influence RMR or DIT. PMID- 2246962 TI - The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia. AB - Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 +/- 0.6 mmol.L-1, mean +/- SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 +/- 0.2 mmol.L-1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3(3H) glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU.kg-1.min-1. At identical fasting glucose concentrations (HT, 5.2 +/- 0.2; C, 5.2 +/- 0.2 mmol.L-1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 +/- 1.2; C, 4.6 +/- 0.4 mU.L-1; P = .02), and C peptide (HT, 1.7 +/- 0.2; C, 1.1 +/- 0.1 microgram.L-1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 +/- 0.3; C, 10.9 +/- 0.7 mumol.kg-1.min-1; NS). At low insulin concentrations (HT, 20.7 +/- 1.4; C, 20.5 +/- 1.4 mU.L-1), hepatic glucose appearance was equally suppressed (HT, 9.6 +/- 0.9; C, 10.5 +/- 1.3 mumol.kg 1.min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246963 TI - Postprandial response of calcium metabolism in postmenopausal women to meals varying in protein level/source. AB - The postprandial response of calcium metabolism to single meals varying in protein source and level was determined in eight postmenopausal women, age 51 to 65 years. Following an overnight fast, subjects consumed a liquid meal containing either 15 g or 45 g of protein from beef (B), cottage cheese (C), or soy isolate (S; 45 g only); one meal provided 0 g protein (basal). Blood was collected before the meal and at 30, 60, 120, and 180 minutes post-meal. Urine was collected every 30 minutes post-meal. Urinary Ca excretion significantly increased following 45-g protein meals when compared with basal meals, but not when compared with 15 g protein meals. Although glomerular filtration rate (GFR) was unaffected by diet, percent renal tubular Ca reabsorption was significantly reduced following C45 or S45 meals. No consistent changes in serum levels of parathyroid hormone (PTH) and calcitonin (Ct) were observed in response to diet. Serum phosphorus levels were significantly reduced following high-protein meals when compared with no-protein meals. Insulin response varied with protein level and source (C45 greater than S45 greater than C15 greater than B45 greater than B15 greater than basal). Significant associations found between insulin and calcium metabolism indicate a possible role of insulin in the mechanism of protein-induced calciuria. PMID- 2246964 TI - The evolution of function and response to arginine challenge and pregnancy of portally and systemically placed islet cell grafts in streptozotocin diabetic mice. AB - Mice made diabetic with streptozotocin received organ cultured fetal islet cell grafts in the portal (PG) or systemic (SG) vascular beds in order to determine whether portal delivery of insulin is an important consideration in graft placement. Grafts were established more quickly in SG mice as shown by body weight and blood glucose estimations. Intraperitoneal arginine was found to be a stronger insulin secretagogue than intravenous glucose with the doses used when serum insulin was measured 5 minutes after injection. Glucose response to an arginine challenge was initially abnormal in both groups of mice, but was identical to normal controls 4 months after transplantation, showing that engraftment is a gradual process. Mice were then mated and their response to the chronic glycemic stress of pregnancy was noted. PG and SG mice had normal fertility rates in contrast to untreated diabetics, none of which became pregnant. Offspring were normal with respect to litter size, body weight, malformation rate, and pancreatic insulin content compared with historical controls. PG and SG mothers behaved normally during pregnancy, with the exception of a raised glycosylated hemoglobin level at day 19.5 gestation (5.5% and 5.5% v 3.7%, P less than .01). We were, therefore, unable to detect any difference between portally and systemically placed islet grafts. PMID- 2246965 TI - Free cholesterol transfer from human lower-density lipoproteins (d less than 1.063) to lipoprotein-deficient serum and high-density lipoproteins. AB - The in vitro transfer of free cholesterol (FC) between human serum lipoproteins in the absence of lecithin:cholesterol acyltransferase (LCAT) activity has been examined. The results show that the amount of FC that the high-density lipoprotein (HDL) and lipoprotein-deficient serum (LDS) fractions were able to capture from low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) was proportional to the amount of FC present in d less than 1.063 lipoproteins. The presence of HDL increased this transfer markedly. These results indicate that, in the absence of LCAT activity, FC can transfer from lower density lipoproteins to higher-density serum fractions, and this transfer might increase under hypercholesterolemic conditions. The possible importance of this phenomena in regard to the exchange of FC between serum lipoproteins and tissue cells is discussed. PMID- 2246966 TI - Effect of selective blockade of oxygen consumption, glucose transport, and Ca2+ influx on thyroxine action in human mononuclear cells. AB - The effect of selective blockade of cellular glucose transporters, Ca2+ influx, and mitochondrial oxygen consumption on thyroxine (T4)-stimulated oxygen consumption and glucose uptake was examined in human mononuclear blood cells. Blockade of glucose transporters by cytochalasin B (1 x 10(-5) mol/L) and of Ca2+ influx by alprenolol (1 x 10(-5) mol/L) and verapamil (4 x 10(-4) mol/L) inhibited T4-activated glucose uptaken and reduced T4-stimulated oxygen consumption by 20%. Uncoupling of mitochondrial oxygen consumption by azide (1 x 10(-3) mol/L) inhibited T4-stimulated oxygen consumption, but had no effect on glucose uptake. We conclude that T4-stimulated glucose uptake in human mononuclear blood cells is dependent on intact glucose transporters and Ca2+ influx, but not on mitochondrial oxygen consumption. However, oxygen consumption is, in part, dependent on intact glucose uptake. PMID- 2246967 TI - Prolonged fasting as conditioned by prior protein depletion: effect on urinary nitrogen excretion and whole-body protein turnover. AB - To study the influence of previous dietary protein depletion on nitrogen (N) loss and protein turnover during a total fast, we measured plasma leucine kinetics and urinary N and 3-methylhistidine (3MH) excretion in obese and normal subjects. In one study, 10 moderately obese women fasted for 2 weeks after adaptation either to a normal maintenance intake of 80 g protein and 150% of estimated resting energy expenditure (control group), or to 10 days of a 950-kcal, 200-g carbohydrate, 4-g protein diet (depletion group), with measurement of postabsorptive (or fasting) plasma leucine turnover on the maintenance diet and after 3 and 10 days of fasting. As measured after 10 days of fasting, body N loss was blunted by 17% when preceded by the protein-deficient diet. Plasma leucine flux and oxidation of the control group increased in early fasting and decreased by 10 days, in accordance with previous reports. Results for the depletion group were similar in absolute magnitude, despite the preceding protein-deficient diet. In a second study of five normal men, leucine kinetics were measured on a maintenance diet, after 10 days of a protein-free diet, and after 3 days of fasting. After protein depletion, leucine flux decreased by 19% (P less than .05). After 3 days fasting, leucine flux was 16% higher than on the maintenance diet (P less than .05), but 44% higher than the value on the protein-free diet 3 days earlier (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246968 TI - Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus. AB - Factors that potentially affect the generation of excess low molecular weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes of patients with systemic lupus erythematosus (SLE) were studied because this species of DNA is consistently found and this DNA may play a role in the pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%. Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation of excess LMW DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase, mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin), a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine) did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no effect and cysteine was toxic. Because scavengers of free radicals might be useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was administered to six acutely ill patients with SLE. A therapeutic benefit was not demonstrated, and some patients had exacerbation of disease. Lymphocyte cell growth from control and lupus subjects was stimulated when cysteamine, 1 x 10(-5) to 1 x 10( 4) mol/L was added to the media, but inhibited at concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use as a free radical scavenger. PMID- 2246969 TI - Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study. AB - The fatty acid composition of serum cholesterol esters was investigated in 325 subjects with normal glucose tolerance, 97 subjects with impaired glucose tolerance (IGT), and 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM) identified by population-based screening. The proportions of palmitic acid (16:0) and palmitoleic acid (16:1) in serum cholesterol esters increased from the normal glucose tolerance group to the IGT and diabetic groups. On the other hand, the proportion of linoleic acid (18:2) was lower in diabetic subjects than in the subjects with IGT or normal glucose tolerance. The proportions of gamma-linolenic (18:3), dihomo-gamma-linoleic (20:3), and arachidonic (20:4) acids were highest in diabetic subjects and lowest in subjects with normal glucose tolerance. Our findings suggest that subjects with NIDDM or IGT have had higher dietary intake of saturated fatty acids. Both serum insulin and blood glucose concentrations probably have an effect on the elongation and desaturation of fatty acids, but the metabolism of linoleic acid to prostaglandin precursors seems to be different in different types of diabetes, NIDDM patients showing no abnormalities. The possibility that the fatty acid composition of plasma and membrane lipids has a role in insulin resistance and blood glucose regulation deserves further investigation. PMID- 2246970 TI - Dose-response characteristics for glucose-stimulated insulin release in man and assessment of influence of glucose on arginine-stimulated insulin release. AB - Glucose potentiates arginine-induced insulin release. We investigated the dose response characteristics for both phases of glucose-induced insulin release in normal man, and studied the influence of hyperglycemia on arginine-induced insulin secretion. Dose-response curves of plasma C-peptide increments achieved during 60-minute hyperglycemia clamps (7, 11, 17, 24, and 32 mmol/L) with and without a primed continuous infusion of arginine (infusion rate, 15 mg/kg/min) were analyzed with a modified Michaelis-Menten equation. The ED50 (half-maximally stimulating blood glucose concentration) of first-phase insulin release (determined from plasma C-peptide increments at 5 minutes) was significantly lower than the ED50 for the second phase (60 minutes; 8.4 +/- 0.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .002). Combined glucose-arginine stimulation significantly increased insulin release. Vmax of both phases of glucose-arginine stimulated insulin release were positively correlated (r = .75, P less than .05). The ED50 of the influence of glucose on first-phase arginine-induced insulin release was significantly lower than the ED50 for the second phase (9.0 +/- 1.1 v 12.7 +/- 1.0 mmol/L, respectively, P less than .02). For each insulin secretion phase separately, the ED50 for the influence of hyperglycemia on arginine-induced insulin release were not significantly different from the ED50 for glucose induced insulin secretion (without arginine). When dose-response curves of plasma insulin increments were analyzed with the same equation, the ED50 of second-phase glucose-induced plasma insulin increments was significantly higher than the ED50 assessed from the plasma C-peptide increments (21.6 +/- 2.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246971 TI - Insulin-mediated increase in glucose 1,6-bisphosphate is attenuated in skeletal muscle of insulin-resistant man. AB - The purpose of this study was to determine the effect of insulin infusion on the glucose 1,6-bisphosphate (glucose 1,6-P2) content in skeletal muscle of insulin resistant man. Euglycemic (approximately 100 mg/dL) hyperinsulinemic clamps were performed on seven men with chronically elevated fasting plasma glycemia (228 +/- 13 mg/dL, mean +/- SE) who were insulin resistant (HIR) and five men with normal fasting glycemia (115 +/- 5 mg/dL) who were insulin resistant (NIR). Insulin was infused at successive rates of 40 and 400 mU/m2/min, and biopsies were obtained from the quadriceps femoris muscle before and after insulin infusion. The results were compared with those of normoglycemic insulin-sensitive (NIS) men. The insulin-resistant groups had significantly higher percent body fat values than did the NIS group. Glucose 1,6-P2 increased from 70 +/- 6, 49 +/- 9, and 67 +/- 3 mumols/kg dry weight in the basal state to 135 +/- 12 (P less than .001 v basal), 67 +/- 11 (P greater than .05) and 79 +/- 3 (P greater than .05) after 40 mU insulin in NIS, HIR, and NIR, respectively. Glucose 1,6-P2 increased to 147 +/- 12 (P less than .001 v basal), 91 +/- 15 (P less than .01) and 99 +/- 13 (P less than .05) mumols/kg dry weight after 400 mU insulin in NIS, HIR, and NIR, respectively. The increase in glucose 1,6-P2 in response to 40 mU insulin was only 28% and 18% in HIR and NIR, respectively, of that in NIS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246972 TI - Adaptive regulation of lipoprotein lipase and salt-resistant lipase activities in essential fatty acid deficiency: an experimental study in the rat. AB - Lipoprotein lipase (LPL) activities of postheparin plasma, heart, lungs, and adipose tissue, and salt-resistant lipase (hepatic lipase, SRL) activities of postheparin plasma, liver, and adrenals were examined in essential fatty acid deficient (EFAD) rats and in age-matched controls. The LPL activity of heart was higher in the deficient than in the control rats, but did not differ in the other tissues. The SRL activity of postheparin plasma was twofold higher, and that of liver and adrenals approximately 50% higher in the group with EFA deficiency. It is suggested that SRL exhibits an adaptive up-regulation in EFA deficiency. This up-regulation may be linked to a role for the enzyme in the transport of polyenoic fatty acids. PMID- 2246973 TI - Substrate metabolism during modest hyperinsulinemia in response to isolated hyperketonemia in insulin-dependent diabetic subjects. AB - To assess the metabolic effects of moderate hyperketonemia, six young male type 1 diabetic patients received a 200-minute intravenous (IV) infusion of (1) 0.9 mmol 3-hydroxybutyrate (3-OHB)/kg/h, and (2) saline. To ensure comparable metabolic conditions, a low-dose hyperinsulinemic euglycemic glucose clamp was performed from 5 hours before and throughout 3-OHB/saline infusions. The forearm technique was employed to estimate substrate fluxes in muscle. Infusion of 3-OHB caused: (1) increases (P less than .05) in circulating levels of 3-OHB (from 112 +/- 73 mumol/L to 825 +/- 111 mumol/L) and forearm arteriovenous differences of 3-OHB (from 19 +/- 10 mumol/L to 145 +/- 46 mumol/L), as well as an eightfold increase of plasma acetoacetate. (2) Decreased (P less than .05) levels of nonesterified fatty acids (NEFA; from 466 +/- 85 mumol/L to 201 +/- 14 mumol/L) and glycerol (from 39 +/- 7 mumol/L to 11 +/- 4 mumol/L) and decreased (P less than .05) arteriovenous differences of glycerol (from -16 +/- 8 mumol/L to -3 +/- 2 mumol/L). (3) Increased (P less than .05) levels of serum growth hormone (GH; from 4.1 +/- 1.5 micrograms/L to 15.9 +/- 8.0 micrograms/L). No change was recorded in circulating concentrations of free insulin, glucagon, glucose, lactate, or alanine. Nor were arteriovenous balances of these intermediary metabolites, isotopically determined glucose turnover or amounts of exogenously administered glucose affected. In conclusion, in type 1 diabetic man, the main regulatory effect of isolated hyperketonemia appears to be a direct negative feedback inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246975 TI - Effects of insulin on glucagon-stimulated glucose production in the conscious dog. AB - The relative importance of insulin and glucagon as primary regulators of glucose metabolism in vivo was assessed in 18-hour fasted conscious dogs. Glucose turnover was determined using [3-3H]glucose and gluconeogenesis was assessed using tracer ([14C]alanine) and A-V difference techniques during a 40-minute control period and a 3-hour period during which various hormonal perturbations were brought about. During the infusion of somatostatin and basal intraportal replacement amounts of insulin and glucagon for the entire study, the plasma glucose concentration (109 +/- 5 mg/dL), glucose production (3.24 +/- 0.30 mg/kg/min), and glucose utilization (3.17 +/- 0.32 mg/kg/min) remained unchanged. When the glucagon infusion rate was increased fourfold at the end of the control period, the plasma glucose level increased from 107 +/- 4 to 225 +/- 23 mg/dL by 1 hour and remained elevated. Glucose production increased from 3.14 +/- 0.29 to 7.66 +/- 0.51 mg/kg/min by 15 minutes and decreased to 4.23 +/- 0.35 mg/kg/min by 3 hours. Glucose utilization rose from a basal value of 3.20 +/- 0.26 to 5.46 +/- 0.27 mg/kg/min by 3 hours. When a fourfold increase in the insulin infusion rate was brought about at the end of the control period, glucose production decreased from 2.83 +/- 0.20 to 1.16 +/- 0.57 mg/kg/min by 1 hour, after which it increased slightly (1.62 +/- 0.81 mg/kg/min). Glucose utilization increased from 2.92 +/- 0.30 to 8.12 +/- 1.12 mg/kg/min by 3 hours. Euglycemia was maintained by glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246974 TI - Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion. AB - Using double-blind, placebo-controlled procedures, the effects of methionyl-human growth hormone (met-hGH) on the tumor cytotoxic activity of natural killer (NK) cells were studied in seven healthy adults using a repeated measures experiment. Subjects were assigned at random to either a placebo (bacteriostatic water) treatment condition or a met-hGH (16.0 mg/wk of Protropin) treatment condition, then crossed-over to the alternative treatment. Treatments were delivered on alternate days (3 d/wk) for 6 weeks. Without bias from the met-hGH treatment, there was no evidence for GH hyposecretion as measured by the peak circulating GH response to exercise stimulation (14.1 +/- 3.1 ng/mL) or insulin-like growth factor (IGF-I) levels (0.82 +/- 0.09 U/mL). When compared with placebo, met-hGH induced a significant overall increase in the percent specific lysis (%SL) of K562 tumor target cells (placebo 22.2 +/- 1.7 v met-hGH 28.5 +/- 2.1 %SL; P = .008). NK activity was increased within the first week of treatment and this level was maintained throughout the remaining period of supplementation. There was a trend (P = .057) for the met-hGH-induced percent change in NK activity (NK%) to be inversely related to placebo IGF-I levels (r = -.761), while there were significant positive correlations between NK% and the met-hGH-induced percent changes in IGF-I (r = .727; P = .035), the fat-free mass (FFM)/fat mass (FM) ratio derived by hydrodensitometry (r = .792; P = .012), and the endogenous GH response to exercise (r = .469; P = .034).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2246976 TI - Decrease in A1 adenosine receptors in adipocytes from spontaneously hypertensive rats. AB - We have investigated whether the insulin resistance reported to occur in hypertension is due to decreased insulin receptors or to adenosine receptors in adipocyte membranes. Membranes were isolated from adipocytes from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKy) rats and assayed for insulin receptors and A1 adenosine receptors. The two groups of membranes bound 125I-insulin equally, but in contrast the SHR membranes bound approximately 25% less 125I-HPIA ([(-)-N6-p-hydroxyphenylisopropyl adenosine], an A1 adenosine receptor agonist) than the WKy (P less than .005). Scatchard analysis demonstrated that this was due to a lower number of receptors in the SHR. The affinity of the receptor for HPIA was approximately 0.7 nmol/L in both groups. 5' Nucleotidase activity was approximately 40% higher in membranes from SHR than WKy (P less than .001), indicating that adipocytes from SHR have a higher capacity for adenosine production. This may cause increased adenosine concentrations in the SHR adipose tissue, leading to adenosine receptor down-regulation. Since we have previously demonstrated that adenosine receptor down-regulation can lead to insulin resistance, these findings may partly account for the insulin resistance of hypertension. PMID- 2246977 TI - Child health in the Third World. PMID- 2246978 TI - The homebirth debate. PMID- 2246979 TI - No-fault insurance in obstetrics. PMID- 2246980 TI - Surrogacy. PMID- 2246981 TI - The Peden case and expert witnesses. PMID- 2246983 TI - Mirror of medicine. PMID- 2246984 TI - Allergy to stinging and biting insects in Queensland. AB - Over an eight and a half year period 742 patients were assessed for allergy to stinging and biting insects in Queensland; 452 (61%) had allergic reactions to honey bees, 244 (33%) to wasps, 30 (4%) to various ants, 11 (1.5%) to march flies (Tabanus sp.) and five to tick infestation. One hundred and fifty one patients (20%) presented with large local swelling only (RXN1), 98 (13%) with urticaria and/or facial angioedema distant from the sting site (RXN2) and 492 (66%) with subjective or objective evidence of dyspnoea or hypotension (RXN3). Allergy testing was performed with honey bee and wasp venoms by skin testing or by Radioallergosorbent testing. Fifty nine patients (30%) with RXN3 responses to wasps failed to react to either test, while this applied to only 19 (6%) of the patients with RXN3 responses to bee stings. Thus, a large number of wasp-allergic patients with RXN3 responses could not be offered immunotherapy. A similar problem exists in the lack of availability of specific reagents for anti- and tick-induced dyspnoea or hypotension. A whole-body insect extract of march fly, however, appears useful. PMID- 2246985 TI - Propolis. PMID- 2246986 TI - Eye injuries among pennant squash players and their attitudes towards protective eyewear. AB - A questionnaire survey on eye injuries and attitudes towards protective eyewear was conducted among 165 metropolitan pennant squash players; 163 (99%) valid responses were received. The incidence of eye injuries in the survey sample was found to be 17.5 per 100,000 playing hours with a significant proportion (26%) indicating that they had suffered at least one eye injury. Racquets were more common as the source of injury (61%) than squash balls. A large proportion of those injured consulted a doctor (63%) with approximately one-third (or 5% of the total survey sample) having been admitted to hospital for the injury. Only 8% of the sample used appropriate protective eyewear with an additional 2% believing their prescription lenses were a form of protection. The main reason given for using protective eyewear was previous injury to self or others (65% of cases). Doctors and media promotion rated poorly in causing players to use eyewear (6% for each). Most respondents believed eyewear to be of benefit, but fewer than half felt that eyewear should be made compulsory for all players. Only 6% of players said that they would give up the game if use of eyewear was made compulsory. PMID- 2246987 TI - Ten years of snake bites at Fremantle Hospital. AB - Seventy-six patients (30% children) were admitted to Fremantle Hospital over 10 years with suspected snake bite. Twenty-nine patients were definitely bitten, with 26 bites being witnessed. Of the 13 patients definitely envenomated, 11 had a coagulopathy although seven were asymptomatic; four other patients may have been envenomated. The dugite (Pseudonaja affinis) was probably responsible for most envenomations. Eleven of the 13 envenomated patients received antivenom (six brown snake, four polyvalent and one tiger snake antivenom). The patient envenomated by the tiger snake (Notechis ater occidentalis), a 13-year-old girl, was initially incorrectly treated with brown snake antivenom at a country hospital, and did not receive appropriate antivenom until 50 hours after the bite. She developed profound paralysis, rhabdomyolysis and renal failure, and required prolonged ventilation during her 53-day hospital admission, but survived without disability. Snake bite wounds should not be washed, so that venom can be identified from the wound. Attempts to kill snakes are dangerous, often leading to bites on the fingers. First aid measures of a pressure bandage and immobilisation, used in 13 of the 29 cases (45%), should be more widely publicised. PMID- 2246988 TI - A review of pre-hospital defibrillation by ambulance officers in Perth, Western Australia. AB - Ventricular fibrillation (VF) is the most common presenting rhythm in cardiac arrest occurring outside hospitals. All cases of VF treated with a defibrillation only protocol by ambulance officers were reviewed. Of the 231 cases entered into the study, 40 (22.7%) patients survived to 28 days after discharge from hospital. The proportion of survivors in this study is similar to that receiving full paramedic services. Further, where time to defribillation is short, the chance of survival improves. The key determinant in survival from VF occurring outside hospital appears to be how rapidly defibrillation can be initiated. PMID- 2246989 TI - Planned homebirths in South Australia 1976-1987. AB - Homebirths booked with a group of general practitioners and midwives in South Australia in 1976-1987 are described using data obtained from midwives' and hospital records. The births represented 84.7% of all births occurring at home in South Australia in 1984-1987, as assessed by official birth registrations. Of the 799 women intending to deliver at home, 136 (17.0%) required transfer to hospital before or during labour. A further 38 mothers or babies (4.8%) required transfer after delivery. The women tended to be of a relatively high socioeconomic status and older age distribution when compared with women who had hospital births as identified from the State perinatal data collection. Some had recognised pregnancy risk factors. They had lower frequencies of ultrasound examination, induced labour, epidural analgesia, episiotomy, forceps delivery and caesarean section, and a low frequency of use of oxytocics for the third stage. Their rates of postpartum haemorrhage and, in particular, perinatal mortality were higher. Potential sources of risk and difficulty in homebirth care and evaluation of this care are identified and an approach to providing an effective homebirth service is proposed. PMID- 2246990 TI - Planned homebirths in Western Australia 1981-1987: a descriptive study. AB - Descriptive data on all 995 singleton planned homebirths in Western Australia from 1981 to 1987, including transfers to hospital, were collected from homebirth records and other sources. Data on singleton Caucasian births in Western Australia for the same years are also presented. The proportion of homebirths rose from 3.5 per 1000 to 7.9 per 1000 singleton births over the study period. Women who had planned homebirths were predominantly Caucasian, similar in parity and marital status but taller and slightly older. They were not all at low risk as some had had complications in previous pregnancies. Transfers to hospital (antenatal, intrapartum or postpartum) occurred in 24.6% of planned homebirths, about 20% in each year transferring before delivery. The main reason for transfer was failure to progress in labour. Postpartum haemorrhage occurred in 8.5% of women, 1.9% of infants were of low birthweight and 3.2% were born before term. The perinatal mortality proportion was 10.1 per 1000 total births. Based on the results of this study homebirth practice in Western Australia appears to be characterised by appropriate diagnosis and referral of complications. As randomised controlled trials of planned home and hospital births are not possible, data such as these are important in evaluating homebirth practice and assisting in the formulation of policy. PMID- 2246991 TI - Safe use of electroconvulsive therapy in pregnancy. AB - A 22-year-old woman who was 32 weeks pregnant was given a course of electroconvulsive therapy (ECT) as a life-saving measure to treat a severe psychotic illness. The ECT was highly effective and careful monitoring of both the mother and the fetus demonstrated that this was a safe procedure. PMID- 2246993 TI - "Generic" packaging--a possible solution to the marketing of tobacco to young people. AB - Creating a brand image is a key part of marketing tobacco products. It makes subtle promotion of a product possible in spite of national and State barriers (such as advertising bans) through print advertising and televised coverage of international sponsored sporting events. This article argues for the introduction of mandatory generic packaging of all tobacco products as an essential component of a complete ban on tobacco advertising and promotion. The rationale for such a move is that tobacco should be treated as the toxic, addictive and ultimately lethal substance that it is, and responsible governments should not allow cleverly designed and enticing packaging to promote a product if they have decided to end promotion of that product. PMID- 2246992 TI - Unidentified trematode eggs in faeces of Australian aboriginal children. AB - In routine surveys for intestinal parasites among Aboriginal/Torres Strait Islander populations, eggs of unidentified trematode species have been found in the faeces of three children. In two of these, the eggs appeared to belong to a schistosome, or perhaps monogenean, species, and in the third, they were most likely from a monostome of dugongs. Although these probably represent cases of spurious parasitism, one or more may have been a true infection. PMID- 2246994 TI - Studying in America. You take the fellowship--what about the family? PMID- 2246995 TI - After the fellowship--basic research? PMID- 2246996 TI - How much parenting is a health responsibility? PMID- 2246997 TI - Antismoking products. AB - Nicotine is the addictive substance in tobacco and its withdrawal is responsible for a range of unpleasant symptoms after smoking cessation. Although it produces acute physiological effects, nicotine alone is not carcinogenic and does not appear to cause the vascular disease associated with smoking. Nicotine replacement has been shown to be a safe and effective pharmacological treatment for tobacco dependence in certain smokers. Its efficacy is greatest when prescribed for those who are motivated and highly nicotine-dependent. It is probably not indicated for smokers with a low degree of nicotine dependence. Studies of nicotine chewing gum conducted in special referral clinics have generally produced positive results, whereas those conducted in community practice settings have shown a smaller benefit when compared with placebo. When the results of all published placebo-controlled trials are pooled the typical improvement in smoking cessation rate is 40% (odds ratio continued smoking 0.6; 95% confidence interval 0.5-0.71; P less than 0.00001). The best results with nicotine chewing gum have been obtained with multicomponent programmes which have included some counselling and ongoing follow up and support. Early reports of success with a transdermal nicotine preparation suggest that it may have similar efficacy to nicotine gum. Clonidine administered orally or transdermally has also been shown to reduce tobacco withdrawal symptoms but requires more convincing evidence of long-term efficacy before it can be recommended for routine use. Currently available over-the-counter products, apart from nicotine chewing gum, have not been shown to be effective. PMID- 2246998 TI - Doctor Governor, Sir William MacGregor--and the Queensland medical school. PMID- 2246999 TI - The Peden case: an Australian forensic disaster. PMID- 2247000 TI - Concern for colleagues or permission to be ill. The story of the Medical Benevolent Association of New South Wales and the Doctors' Health Advisory Service (NSW). PMID- 2247002 TI - Severe brain injury: intensive family involvement in community-based rehabilitation. AB - A 15-year-old boy, severely brain injured as a result of a motor vehicle accident, was in coma for six weeks. Five months after the injury, while still severely disabled, he was taken home and treated by an intensive, organised domiciliary programme of community-based rehabilitation supplemented by additional help from the local hospital. The patient regained function, and the programme was emotionally rewarding for the relatives, friends and volunteers. Significant cost savings to the State may be obtained with this method of management. PMID- 2247001 TI - Rare earth deposits in a deceased movie projectionist. A new case of rare earth pneumoconiosis? AB - The subject described in this case report, a movie projectionist, had approximately 25 years of occupational exposure to carbon arc lamp fumes. The carbon arc deposits were visible in histological sections as small granules within macrophages of the tracheobronchial lymph nodes and hepatic Kupffer's cells. Electron microprobe analysis by energy dispersive analysis of x-rays showed the granules to be composed of the rare earth elements cerium, lanthanum and neodymium, which are the major constituents of carbon arc rods. Tissue concentrations, as determined by inductively coupled plasma spectroscopy, were approximately 250-2000 times those of unexposed controls, and there was evidence of their redistribution throughout the reticuloendothelial system. There were no respiratory symptoms, or radiographic or histological pulmonary changes attributable to the progressive accumulation of the rare earth elements, and as such the patient cannot be considered to have suffered from pneumoconiosis. Twenty-one published cases of rare earth pneumoconiosis, mainly in photoengravers exposed to carbon arc fumes, are reviewed and suggest that rare earth oxides are not innocuous dusts. With the increasingly widespread use of rare earth elements there is a likelhood that further occupational groups may have significant but unrecognised exposure. PMID- 2247003 TI - A transcultural knight. PMID- 2247004 TI - High incidence of subacute sclerosing panencephalitis (SSPE) in young children in Papua New Guinea. PMID- 2247005 TI - Privacy and medical research: most people support current practice. PMID- 2247006 TI - Update of rubella immunisation in a school-based campaign. PMID- 2247007 TI - Methadone. PMID- 2247008 TI - Phacoemulsification in cataract surgery. PMID- 2247009 TI - "Clusters" of patients with motor neurone disease. PMID- 2247010 TI - Rapid HIV-antibody testing. PMID- 2247011 TI - Severe respiratory and renal failure in serovar hardjo related leptospirosis. PMID- 2247012 TI - Medication-related conjunctivitis. PMID- 2247013 TI - Capping needles. PMID- 2247014 TI - Dangers of immunotherapy for the treatment of asthma in children. PMID- 2247015 TI - [Prescription responsibility--always reasonably regulated?]. PMID- 2247016 TI - [Interleukin-1 and interleukin-2]. PMID- 2247017 TI - [Physical exercise for prevention and therapy]. PMID- 2247018 TI - [Arteriosclerosis. Cellular biology aspects]. PMID- 2247019 TI - [Drug information. Instructions for storage and administration. Insulin preparations]. PMID- 2247020 TI - Mifepristone (RU 486). PMID- 2247021 TI - Comparative effects of ethanol, acetaldehyde and acetate on arterioles and venules in skeletal muscle: direct in situ studies on the microcirculation and their possible relationship to alcoholic myopathy. AB - The precise effects ethanol (ETOH), acetaldehyde (ACT) and acetate (AC) exert on microscopic resistance and capacitance vessels in skeletal muscle is unknown. In situ studies on the skeletal (cremaster) microvasculature of the rat, using high resolution television microscopy, were undertaken. Acute administration (topical, intra-arterial or iv) of ethanol (0.001-10%) to young rats produced a concentration-related vasoconstriction of arterioles (18-45 microns) and muscular venules (25-50 microns), ranging from a 7 to 80% reduction in microvessel lumen sizes. Acute administration of either ACT or AC, however, produced concentration related vasodilatation of these same microvessels. No known amine or opiate pharmacologic antagonist or cyclooxygenase inhibitor could attenuate or prevent ETOH, ACT and AC from eliciting their unique microvascular responses. These new, direct in-situ microcirculatory findings clearly demonstrate: 1) ETOH exerts constrictor, and not dilator, effects on skeletal muscle microscopic resistance and capacitance vessels; 2) both ACT and AC exert dilator, and not constrictor, effects on these muscle microvessels; and 3) the effects of alcohol can not be due to metabolism to ACT or AC. A progressive increase in ischemia of the skeletal muscle microscopic resistance and capacitance vessels, over a period of time (weeks to years), could result in the well-known syndrome of alcoholic myopathy. PMID- 2247022 TI - Oxygen sensitivity of a multichannel antimony microelectrode for tissue surface oxygen pressure measurements. AB - The measuring properties of antimony electrodes were improved by the introduction of highly purified crystallographically oriented monocrystalline antimony (COMA). COMA electrodes are sensitive to pH and pO2. For measurements of either pH, pO2, or both, the pH and the pO2 sensitivities must be known and the components of the composite electrode signal must be separable. The oxygen sensitivity of COMA electrodes in vivo have been shown to be higher than in vitro in the pO2 range below 10 kPa. The present study was performed in an animal model to investigate the oxygen sensitivity and to further evaluate the tissue pO2 measuring properties of a miniaturized six channel COMA microelectrode. The results show that the COMA microelectrode has negligible drift, a response time of less than 5 s and high sensitivity and reproducibility for tissue pO2 measurements when the pH part of the electrode signal is eliminated. The oxygen sensitivity found (8.5 +/- 0.4 (mV/pO2) (mean +/- SEM)), is described by a direct linear function in the oxygen tension range studied. It is concluded that tissue pO2 can be calculated after elimination of the pH part of the electrode signal. A multichannel COMA microelectrode possess characteristics suitable for in vivo oxygen measurements and is therefore an interesting complement to traditional tissue oxygen sensors. PMID- 2247023 TI - Erythrocyte individual phospholipids and erythrocyte membrane fluidity in subjects with vascular atherosclerotic disease with and without diabetes mellitus of type 2. AB - In a group of 12 subjects (5 men, 7 women) with vascular atherosclerotic disease (VAD) and in a group of 17 subjects (9 men, 8 women) with VAD and with non insulin dependent diabetes mellitus (NIDDM) we evaluated the red cell membrane individual phospholipids and their relationships with the erythrocyte membrane fluidity. Examining the group of non diabetic subjects with VAD, it is evident that no difference is present between normals and this group regarding individual phospholipids; in this group is present a slight correlation between the erythrocyte membrane fluidity (expressed as Iex/Im ratio) and phosphatidylethanolamine only. Examining the group of VAD subjects with NIDDM it is evident that between normals and this group a significant difference is present for phosphatidylcholine and phosphatidylserine; in this group no relationship is evident between red cell membrane individual phospholipids and Iex/Im ratio. PMID- 2247024 TI - Morphometric changes in pericyte-capillary endothelial cell associations correlated with vasoactive stimulus. AB - The arterially-derived capillaries of the eel rete mirabile are heavily invested with highly arborized pericytes. By perfusing vasoactive agents through these capillaries, measuring changes in outflow volume and analyzing alterations in capillary and pericyte morphology a set of vasoactive agent-correlated changes were quantified. Morphometric analysis of the capillary ultrastructure revealed that alterations in flow and appearance were associated with changes in the extension of pericyte processes. These responses of the arterial pericytes to the vasoactive agents used in this study suggest that pericyte contraction alters the architecture of the arterially-derived capillaries of the rete in a manner which affects their permeability. PMID- 2247025 TI - Umbilical vessels endothelium and vascular reactivity. AB - In vitro preparations of isolated umbilical vessels are ideal for the study of vasoactive substances. These vessels display vascular reactivity in response to numerous substances, although the mechanism of action of many of these agents is unknown. The present study was undertaken to study the role of the endothelium in the vasoactivity of these preparations, and to examine their cellular integrity. Umbilical artery and vein were studied using conventional isometric techniques, and using high power light microscopy. We found that umbilical vessel rings had no relaxant response to agents believed to release endothelium-derived relaxant factor (EDRF). Mechanical and chemical treatment to remove endothelium did not significantly alter vascular response to known contractile agonists. Cellular morphology is well maintained in ring preparations. Finally, mechanical rubbing of the intima of these rings is more reliable in endothelium removal, as compared to chemical removal with the detergent saponin. PMID- 2247026 TI - Methods in behavioral toxicology and teratology. A symposium. Little Rock, Arkansas, October 4-6, 1989. Proceedings. PMID- 2247027 TI - Use of the NCTR Operant Test Battery in nonhuman primates. AB - A battery of behavioral tasks, designed to monitor complex "cognitive" functions in nonhuman primates, has been in use for several years at the National Center for Toxicological Research. Subjects performing in this Operant Test Battery (OTB) work for food reinforcers and correct performance in each task contained in the OTB is thought to depend upon a relatively specific brain function. The specific tasks and the functions that they are thought to model are: delayed matching-to-sample (DMTS), short-term memory and attention; incremental repeated acquisition (IRA), learning; temporal response differentiation (TRD), time perception; progressive ratio (PR), motivation; and conditioned position responding (CPR), color and position discrimination. Data from various studies indicate that, in general: 1) OTB responding between subjects follows a normal or near-normal distribution; 2) performance in one task does not correlate very highly with performance in any of the other tasks; 3) females acquire correct OTB responding more rapidly than do males; and 4) the profile of disruption of task performance by acute drug administration varies depending upon drug class. PMID- 2247028 TI - Computer pattern recognition: an automated method for evaluating motor activity and testing for neurotoxicity. AB - An economical computer-based pattern recognition system, which has been designed to observe, classify, analyze, and record the spontaneous motor activity of the laboratory rat, is presented. The advantages and disadvantages of the system are assessed in terms of characteristics generally held to be desirable for a motor activity screen of potentially neurotoxic chemicals. Data from rats exposed to 1 mg/kg d-amphetamine are compared with similar data previously taken with an earlier version of the system at another laboratory. PMID- 2247029 TI - Automated behavioral procedures for infant monkeys. AB - A method is described for testing infant monkeys on a variety of operant tasks as soon as they can self-feed, typically within the first week of life. Each infant was housed during the 16-21-hour experimental session in a cage to which operant behavioral equipment was attached. Computer control of the experimental contingencies and data acquisition allowed a relatively large number of monkeys to be tested simultaneously, as well as detailed analysis of response parameters. Infant monkeys are capable of learning a number of tasks that assess learning and memory, including visual discrimination and reversal, simultaneous discrimination, and spatial and nonspatial matching to sample. Infant monkeys also perform like older animals on intermittent schedules of reinforcement. The long experimental sessions allowed determination of feeding pattern over the course of the night. Analyses of these variables have proved sensitive to the effects of developmental exposure to neurotoxicants such as lead and caffeine. PMID- 2247030 TI - Repeated measures designs in behavioral toxicology: application to chronic marijuana smoke exposure. AB - This paper discusses the application of repeated measures methods in the statistical analysis of an experiment in behavioral toxicology. The chronic marijuana smoke exposure study conducted at the National Center for Toxicological Research is used for an example of the types of problems that one encounters in analyzing these types of studies. In particular, the standard univariate analysis most frequently used for repeated measures analyses has some very restrictive assumptions on the form of the covariance matrices. These assumptions are not met in the example discussed and are rarely met in many other problems. Other possible models for analyzing repeated measures when these assumptions are not met are presented and discussed. Other problems specific to the chronic marijuana smoke exposure study that may occur in similar type studies are presented. These include pooling the experimental units into groups with comparable baselines, choosing a function of the measures to be analyzed, dealing with a large data set with many observation times and missing data, unequal group sizes and different designs for different subsets of the experimental animals. The standard univariate repeated measures analysis was chosen to analyze the data even though the violations of the covariance assumptions may lead to finding differences that do not exist (Type I or false-positive errors), since the other methods presented also had covariance assumptions that were not met or had low power. Use of Bonferroni-type multiple comparisons on the single degree of freedom contrasts of interest hopefully reduced the chances of these false-positive results. PMID- 2247031 TI - Dealing with large data sets. AB - Collection, storage and retrieval of large amounts of data from multiple experiments for subsequent reduction, graphing and statistical analysis need not be a burdensome task. Although turnkey systems may offer significant economies for single well-defined and repetitive tasks, they may not permit sufficient flexibility to achieve the diverse aims required by many research programs. Using popular microcomputers to run one or a few experimental subjects may confront the investigator not only with significant bookkeeping problems, but also with an allocation of labor resources to computer maintenance and support that might be better invested in research effort. By using networked minicomputers, economies of scale emerge both in data collection, transfer, reduction, and analysis, as well as in maintenance, support, and scientific effort. PMID- 2247032 TI - Sensory neurotoxicology: use of the olfactory system in the assessment of toxicity. AB - Although many compounds are purported to cause olfactory dysfunction, little experimental research has been done in this area. The nasal epithelium, being one of the first "wet tissues" to come into contact with airborne compounds, should be a good indicator of toxic insult. The same general procedures used to measure visual or auditory function can be applied to the olfactory system, although olfactory stimuli are much more difficult to generate and control. Cadmium exposure, which is frequently cited as causing olfactory dysfunction in humans, did not produce anosmia (loss of smell) in rats, even though there was a large increase in cadmium levels in their olfactory bulbs. Rats exposed to methyl bromide showed a severe disruption in olfactory function as well as in morphology and neurochemical indices. However, functional recovery occurred even in the presence of continuing morphological and neurochemical evidence of damage. A nonsensory function of the olfactory system, transneuronal transport via the primary sensory neurons, may represent a mechanism of entry into the central nervous system for compounds that are normally excluded by the blood-brain barrier. PMID- 2247033 TI - Reflex modification and the detection of toxicant-induced auditory dysfunction. AB - There are numerous environmental chemicals that adversely impact sensory functioning in exposed populations. Test methods are needed that can rapidly and efficiently assess the potential of chemicals to induce sensory toxicity. Reflex modification of the startle response is a technique that provides rapid, objective and quantitative assessments of sensorimotor function. This procedure has been shown to be sensitive to a variety of neurotoxic compounds. Reflex modification can also provide independent estimates of chemical-induced alterations in both sensory and motor function. Future efforts should focus on expanding the use of this procedure in both the identification and characterization of neurotoxic chemicals. PMID- 2247034 TI - Threshold procedures for assessing the impact of agents on brain reward systems. AB - Chemical effects on the reinforcing quality of electrical stimulation of the rat brain can be assessed using a variety of methods, most commonly by observing changes in response rates maintained under specific schedules of reinforcement. We present results demonstrating the utility of procedures for assessing the minimum amount of electrical stimulation required to support rat leverpress responding, that is, the brain-stimulation reward (BSR) threshold. In these threshold procedures, each leverpress produced by the rat decreases the duration of the electrical stimulus delivered to the posterior lateral hypothalamus until the rat fails to respond. The stimulus duration is then reset to its initial value and the procedure begins again. The last stimulus duration in a series supporting a response is defined as the stimulus duration (SD) threshold, and the mean SD threshold is determined daily. Stable SD thresholds are achieved within 2 weeks, and this measure is sensitive to agent-induced changes in rats' response to BSR. To illustrate the utility of this approach, data are presented showing that rats' BSR thresholds changed significantly following exposure to triethyltin or carbon monoxide. The results support the view that threshold methods can be used to dissociate agent-induced effects on brain reward systems and BSR quality from changes in performance or effects on other behavioral processes. PMID- 2247035 TI - A nonhuman primate version of the open field test for use in behavioral toxicology and teratology. AB - As reviewed here, little work has been done on testing nonhuman primates individually in open field paradigms. Hence, normative data from three studies of rhesus monkeys are presented. Important criteria for describing the pattern of activity exhibited by monkeys in the open field are introduced and the effects of gender and differences in rearing are assessed. Differences between this nonhuman primate version of the open field and that typically used with rodents are discussed, including reasons for differences in the variability of behavior between monkeys and rodents and a comparison of coefficients of detection (as an index of the power of the test to detect group differences). Overall, the use of the nonhuman primate version of the open field in behavioral toxicology and teratology is feasible and may fill a significant niche not presently well represented. PMID- 2247036 TI - Approaches for assessing the validity of a functional observational battery. AB - As neurobehavioral assessments during the preliminary stages of chemical testing are more widely undertaken, it is critical that the screening procedures utilized be valid indicators of neurobehavioral function and that they be sensitive, specific, and reliable. Efforts in this laboratory have been directed towards assessing these features in the use of a functional observational battery (FOB). For the purpose of assessing validity, we have examined FOB data which addresses the issues of criterion, predictive, concurrent, and construct validities. The FOB appears to be valid for detecting chemical-induced neurological dysfunction in rats, i.e., shows a good degree of criterion validity. Furthermore, in many instances the effects observed with the FOB may be predictive of symptomatology in humans. When comparisons can be made between effects detected with the FOB and other methods of measuring neurotoxicity (e.g., neuropathology), concurrent validity can also be established. To assess construct validity, effects of neurotoxicants can be classified into functional domains which are described by various measures in the FOB. Approaches for assessing the validity of the test method thus include answering specific research questions directed at assessing criterion, predictive, concurrent, and construct validity. Available data indicate that, in these aspects, the FOB is a valid screening method for the detection of neurotoxicity. PMID- 2247038 TI - What it takes to validate behavioral toxicology tests: a belated commentary on the Collaborative Behavioral Teratology Study. AB - "Design Considerations in Screening for Behavioral Teratogens: Results of the Collaborative Behavioral Teratology Study" (CBTS) was an important conference whose proceedings were published in entirety in Neurobehavioral Toxicology and Teratology (7:532-822; 1985). The proceedings advocate that mandatory "behavioral teratology" testing be made part of regulations governing approval of new drugs and chemicals. This conclusion is unjustified either by the CBTS proceedings or by the present status of "behavioral teratology." First, there is little basis for accepting the validity of testing in developmental psychopharmacology, since so few agents acknowledged to lack the presumed toxic effects are explicitly identified and systematically tested. Second, findings from the CBTS itself can be construed as having indicated poor reliability: Amphetamine, the only drug examined in the CBTS, was selected for study expressly because of prior positive data, yet the study found it to be inactive. Third, the presumed "sensitivity" of behavioral measures is shown to be irrelevant. Fourth, and perhaps most important, the CBTS does not consider the public health risks of mandating nonvalid procedures within regulations. Drugs that are crucial both in therapy as scientific tools may not have been developed had regulations now advocated been in place at the time of their development. PMID- 2247037 TI - Neurobehavioral assessment during the early postnatal period. AB - Few laboratories investigating the neurobehavioral consequences of developmental toxicants assess offspring early in ontogeny other than examining physical maturation, reflex development and perhaps locomotor activity, measures which tap only a limited portion of the neurobehavioral capacities of young organisms. The importance of including a wider range of neurobehavioral assessments during the early postnatal period in developmental toxicology test batteries is discussed. Special considerations for the design of testing early in life are enumerated, and examples are given of suckling, cognitive and psychopharmacological tests that have been shown to be sensitive indicators early in life of the effects of gestational drug exposure. PMID- 2247039 TI - Monkey versus human performance in the NCTR Operant Test Battery. AB - A battery of operant behavioral tasks, designed to monitor complex "cognitive" functions in monkeys, was adapted for use in children. Adaptations were then incorporated into the monkey battery so that monkeys and children performed exactly the same tasks. Food pellets served as reinforcers for monkeys; nickels for children. Correct responding in a task is thought to depend upon relatively specific brain functions including short-term memory and attention, learning, time perception, motivation, and color and position discrimination. Eight 4-year old rhesus monkeys served as subjects, and groups (n = 10 to 20) of 4- to 8-year old children were recruited if they were not known to have any neurological, academic or behavioral problems. In performance of only the learning task was there any significant difference between monkeys and children. This difference was in response rate (not accuracy), with the monkeys responding faster than children. This lone difference in operant responding between monkeys and children was likely due to the fact that monkeys generally use all four appendages to respond whereas children generally do not. PMID- 2247040 TI - The development of a neurobehavioral test battery for use in hazard evaluations in occupational settings. AB - The interest in, and number of, neurobehavioral test batteries for use in occupational settings has increased markedly over the last decade. While this is a welcome development in furthering the cause for greater acceptance of these methods in hazard evaluation and toxicity testing, there are a number of issues that are not being addressed by many test battery designers and users. Without careful consideration of important issues concerning the use of the test batteries, such as the level of testing needed and the selection of appropriate tests, the specificity and sensitivity of tests chosen, the role of computers in test delivery, and the standardisation and interpretation of test results, it is likely that the credibility and utility of neurobehavioral testing will be jeopardized even at this early stage of development. In this paper, the development of a test battery for use in occupational health will be discussed with particular reference to the degree of success in addressing some of the issues described above. A test battery was designed using an information processing model of behavior generation as a base. A continuing programme of standardisation is being carried out on a range of working populations and current results will be discussed. The battery has also been used to evaluate the effects of occupational exposure to a number of hazardous substances including mercury, lead, and most recently, solvents, and to hazardous environments, specifically, underwater work. These results are summarised in terms of the ability of the test battery to detect the effects of particular hazards. PMID- 2247041 TI - Operant behavior as a technique for toxicity testing. AB - Behavioral toxicology is a discipline which has evolved out of the need for data on the effects of toxic agents on the function of the central nervous system. To date the field is divided over the question of which behavioral models to use to detect behavioral toxicities. Operant conditioning and schedule-controlled responding have been used as baselines for testing pharmacological agents for nearly 40 years, and there is no reason that the developing field of behavioral toxicology cannot take advantage of the lessons learned during this 40-year period. Behaviors maintained by operant conditioning procedures have proven to be sensitive to a wide range of chemicals. Using these procedures, behavior has been shown to; be sensitive to toxic agents, provide data relevant to the question of behavioral specificity, provide a stable baseline for extended periods of time, and allow for the assessment of specific functions such as temporal discrimination, learning and memory, and sensory system function. PMID- 2247042 TI - The pigeon as a model for comparative behavioral pharmacology and toxicology. AB - The effects of several drugs and neurotoxins on schedule-controlled responding are reviewed in a number of species. In general, the behavioral effects of these chemicals in different species differ quantitatively more frequently than qualitatively. The sensitivity of schedule-controlled behavior to chemical effects across species does not show any obvious relationship to position on the phylogenetic tree. Pigeons are more sensitive, less sensitive, or equally sensitive to chemicals than other species, depending on the chemical. Because pigeons are inexpensive, have a long life span and are easy to train and handle, they should receive serious consideration as a species of choice for behavioral testing of potential neurobehavioral toxins. PMID- 2247043 TI - Nonhuman primates in behavioral toxicology: issues of validity, ethics and public health. AB - The small, but vital, niche of nonhuman primates in neurotoxicology is examined. Several models of sensory and cognitive function have been especially useful with primates. Their sensitivity to low doses is clear. The validity of data from these models is indicated by their high correlation with data from intoxicated and normal humans, by the degree to which they approximate job functions and other vital human performances, and by their ability to document specific changes in behavioral function which correlate well with morphological and biochemical effects. The use of primates for this research is justified by the absence of adequate alternatives using nonprimate species, in vitro tests or computer programs. A series of experiments on the effects of methylmercury is used to illustrate ethical and scientific issues concerning research with primates. Recent trends are illustrated by data with trimethyltin. PMID- 2247044 TI - Use of monkey neonatal neurobehavioral test batteries in safety testing protocols. AB - Developmental neurobehavioral test batteries are important in assessing potential reproductive and developmental toxicity of new chemicals and drugs. They provide a broad-based evaluation of a range of nervous system functions at a period of life when learning and adaptation are particularly critical. Nonhuman primates are an especially appropriate test species because of their similarities to humans in complexity of brain function and prolonged intrauterine brain development. Problems arise, however, in the analysis and interpretation of data bases generated when a relatively small number of animals are tested on a relatively large number of items. A 2-week neonatal test battery for rhesus monkey infants is described along with approaches to experimental design and statistical analyses that are helpful in providing sound and useful interpretation. PMID- 2247045 TI - Behavioral assessment of young nonhuman primates: perceptual-cognitive development. AB - The Infant Primate Research Laboratory at the University of Washington utilizes a range of test procedures to study perceptual-cognitive development in nonhuman primate infants at high and low risk for poor developmental outcome. These test procedures rely on the visual preferences of infants and are employed in research with both human and animal subjects. The forced-choice preferential looking technique is based on the primate infants' preference for patterned over plain stimuli and allows the early measurement of visual acuity. The novelty paradigm is based on the preference that infants show for novel over familiar stimuli and is used to study intramodal and cross-modal recognition memory. Tests of recognition memory have shown sensitivity in detecting subtle functional alterations associated with perinatal risk factors such as teratogen exposure. The use of measures which assess early patterns of visual attention should be considered in both human and nonhuman primate studies in behavioral teratology. PMID- 2247046 TI - Behavioral toxicology and risk assessment. AB - In order to establish safe exposure levels to toxic chemicals, risk assessment guidelines have been developed. These guidelines evaluate epidemiologic and animal research data on a particular chemical, as well as dose-response relationships, animal to human extrapolation and assessment of exposure levels of populations. Using the guidelines, risk characterization is established in order to determine a strategy for reducing undesirable risk to human populations. Using both human neonatal lead exposure data and results from rodent and primate studies, this review examines the possibility that behavioral measurements are sufficient to provide adequate risk assessment guidelines for lead intoxication of the developing organism. The overall trend in these data during the past 10 years has been to show that exposures to inorganic lead at levels previously considered safe have long-lasting significant alterations in behavioral measures, suggesting that central nervous system function has been altered irreversibly. The conclusion is drawn that behavioral toxicology can provide sensitive, quantitative and reliable data for risk assessment and that in the future these methodologies could be used to set exposure guidelines for other neurotoxic chemicals. PMID- 2247047 TI - Results from the European multicenter study on lead neurotoxicity in children: implications for risk assessment. AB - In order to improve dose-response information on neurobehavioral effects of environmental lead exposure in children, the World Health Organization, Regional Office for Europe (WHO/EURO), in collaboration with the Commission of the European Communities, initiated this international study which was planned, executed and evaluated between 1984 and 1989. Eight groups from eight European countries (Bulgaria, Denmark, Greece, Hungary, Italy, Roumania, W. Germany and Yugoslavia) took part. A common study protocol with inherent quality assurance elements was developed to achieve comparability. Blood-lead concentrations (PbB) were the main markers of exposure. The WISC (4 subtests) for psychometric intelligence, the Bender Gestalt test (GFT version) and the Trail-Making test for visual-motor integration, the Vienna Reaction Device and a delayed RT task for reaction performance, and the Needleman scales for behavior ratings served as behavioral endpoints. All individual studies taken together represent a sample size of 1879 school-age children and cover a PbB range from below 5 to about 60 micrograms/100 ml. Overall statistical evaluation of outcome was done by multiple regression analysis using a uniform confounder model. The strongest and most consistent effects occurred for the Bender Gestalt test (GFT version) and for serial choice reaction performance (Vienna Device). The degree of association with PbB was significant for these variables, although the contribution of PbB to the observed variance never exceeded 0.8%. Psychometric intelligence was also negatively affected, although the consistency of outcome between studies was poor, and the association with PbB only borderline. An effort towards risk assessment was made by calculating the proportion of children at risk, using the observed regression coefficients as well as means and standard deviations. PMID- 2247048 TI - Investigations on the mechanism of the hypocholesterolemic action of 1 ethoxysilatrane. AB - Intraperitoneal administration of the nontoxic silicon compound, 1 ethoxysilatrane, to the rat did not cause proliferation of hepatic mitochondria or of endoplasmic reticulum, nor did it affect mitochondrial oxidative phosphorylation. The activities of cholesterol 7 alpha-hydroxylase in hepatic microsomes and of cholesterol oxidase in mitochondria respectively were unaffected by silatrane treatment. The rate of release of bile, whose composition remained unchanged, also was not increased in silatrane-treated animals. The results indicated that the compound did not affect the pathway of cholesterol degradation. A progressive decrease in the activity of hepatic microsomal 3 hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase was observed on administration of the compound over a period of three weeks. Consistent with this, cholesterol biosynthesis in liver as measured by incorporation of radioactive precursors, acetate and water but not mevalonate, was significantly decreased in silatrane-treated animals. However, enzyme-linked immunosorbent assay revealed that the concentration of HMGCoA reductase protein was not decreased by the treatment indicating that inactivated enzyme was also present in such microsomes. Addition of silatrane to microsomes in the assay system did not cause inhibition indicating that the inactivation is by an indirect mechanism. It is concluded that the hypocholesterolemic action of the compound rested entirely on the inhibition of cholesterol biosynthesis in vivo by inactivation of the rate limiting enzyme HMGCoA reductase. PMID- 2247049 TI - Protein phosphorylation in rat liver mitochondria. AB - Incubation of rat liver mitochondria in the presence of either [32P] Pi or [y32 P] ATP resulted in a phosphorylation of four proteins with Mr 50, 47, 44 and 36 kDa, respectively. The endogenous phosphorylation of these proteins in the presence of [32P] Pi was markedly influenced by the osmolarity of the incubation medium and differentially affected by various effectors of mitochondrial functions, such as Ca2+, oligomycin, FCCP, arsenite and dichloroacetate. In particular, the 36 kDa protein, unlike the other proteins, appears to be phosphorylated also by direct incorporation of [32P], independently of respiratory chain-linked ATP synthesis. The four proteins, located in the mitoplasts, seem to be phosphorylated by different protein kinases, as suggested by the observation that the endogenous phosphorylation of 36 kDa protein resulted selectively increased by addition of exogenous protein kinases, such as casein kinases S and TS. A tentative identification of these phosphorylatable protein is discussed. PMID- 2247050 TI - Role of IME1 expression in regulation of meiosis in Saccharomyces cerevisiae. AB - Two signals are required for meiosis and spore formation in the yeast Saccharomyces cerevisiae: starvation and the MAT products a1 and alpha 2, which determine the a/alpha cell type. These signals lead to increased expression of the IME1 (inducer of meiosis) gene, which is required for sporulation and sporulation-specific gene expression. We report here the sequence of the IME1 gene and the consequences of IME1 expression from the GAL1 promoter. The deduced IME1 product is a 360-amino-acid protein with a tyrosine-rich C-terminal region. Expression of PGAL1-IME1 in vegetative a/alpha cells led to moderate accumulation of four early sporulation-specific transcripts (IME2, SPO11, SPO13, and HOP1); the transcripts accumulated 3- to 10-fold more after starvation. Two sporulation specific transcripts normally expressed later (SPS1 and SPS2) did not accumulate until PGAL1-IME1 strains were starved, and the intact IME1 gene was not activated by PGAL1-IME1 expression. In a or alpha cells, which lack alpha 2 or a1, expression of PGAL1-IME1 led to the same pattern of IME2 and SPO13 expression as in a/alpha cells, as measured with ime2::lacZ and spo13::lacZ fusions. Thus, in wild-type strains, the increased expression of IME1 in starved a/alpha cells can account entirely for cell type control, but only partially for nutritional control, of early sporulation-specific gene expression. PGAL1-IME1 expression did not cause growing cells to sporulate but permitted efficient sporulation of amino acid-limited cells, which otherwise sporulated poorly. We suggest that IME1 acts primarily as a positive regulator of early sporulation-specific genes and that growth arrest is an independent prerequisite for execution of the sporulation program. PMID- 2247051 TI - Analysis of a gene cluster for sarcotoxin II, a group of antibacterial proteins of Sarcophaga peregrina. AB - Sarcotoxin II is a group of antibacterial proteins of Sarcophaga peregrina (flesh fly) with related primary structures. We have cloned three genes in this family. These genes formed a tandem array with about 2-kb intervals, and one of them was present in the opposite strand. The putative amino acid sequences of the proteins encoded by these genes were very similar except for a deletion in one of them. All of the genes were found to be activated transiently in the same way when the larval body wall was injured, suggesting that the encoded proteins are acute phase-responsive proteins for protecting the insect from bacterial infection. PMID- 2247052 TI - A suppressor of an RNA polymerase II mutation of Saccharomyces cerevisiae encodes a subunit common to RNA polymerases I, II, and III. AB - RNA polymerase II (RNAPII) is a complex multisubunit enzyme responsible for the synthesis of pre-mRNA in eucaryotes. The enzyme is made of two large subunits associated with at least eight smaller polypeptides, some of which are common to all three RNA polymerase species. We have initiated a genetic analysis of RNAPII by introducing mutations in RPO21, the gene encoding the largest subunit of RNAPII in Saccharomyces cerevisiae. We have used a yeast genomic library to isolate plasmids that can suppress a temperature-sensitive mutation in RPO21 (rpo21-4), with the goal of identifying gene products that interact with the largest subunit of RNAPII. We found that increased expression of wild-type RPO26, a single-copy, essential gene encoding a 155-amino-acid subunit common to RNAPI, RNAPII, and RNAPIII, suppressed the rpo21-4 temperature-sensitive mutation. Mutations were constructed in vitro that resulted in single amino acid changes in the carboxy-terminal portion of the RPO26 gene product. One temperature-sensitive mutation, as well as some mutations that did not by themselves generate a phenotype, were lethal in combination with rpo21-4. These results support the idea that the RPO26 and RPO21 gene products interact. PMID- 2247053 TI - A combination of derepression of the lac operator-repressor system with positive induction by glucocorticoid and metal ions provides a high-level-inducible gene expression system based on the human metallothionein-IIA promoter. AB - We and others have introduced the use of the lac operator-repressor system as a method for providing inducible gene expression for gene transfer experiments in animal cells (M. C.-T. Hu, and N. Davidson, Cell 48:555-566, 1987; J. Figge, C. Wright, C. J. Collins, T. M. Roberts, and D. M. Livingston, Cell 52:713-722, 1988). To improve the dynamic range of such an inducible system, we have investigated the effects of combining the relief by isopropyl-beta-D thiogalactoside (IPTG) of negative control by the lac system with positive induction by the natural inducers glucocorticoids and cadmium ion for a system based on the human metallothionein-IIA gene promoter. We used the chloramphenicol acetyltransferase gene as a reporter gene and inserted a lacO sequence into the promoter between the GC box and metal-responsive element 1, between metal responsive element 1 and the TATA box, or between the TATA box and the transcription start site. Surprisingly, all of these insertions had a significant inhibitory effect on promoter activity even in the absence of repressor. However, with these lacO-containing constructs, the levels of gene expression after induction by glucocorticoid, Cd2+, or both were considerably reduced in cells engineered to express the lac repressor. Derepression by IPTG, coupled with induction by both dexamethasone and Cd2+ ion, then provided a high level of induced expression, i.e., by a factor of approximately 100 over the basal level of expression. However, inserting the lacO sequence well upstream just before the glucocorticoid-responsive element had much smaller effects on expression levels in both repressor-negative and repressor-positive cells. This study describes a new, high-level-inducible promoter system for gene transfer experiments. The observed effects are discussed in terms of current models of the mechanisms by which transcription factors control gene expression. PMID- 2247054 TI - Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. AB - We describe the cloning and function of the human XRCC1 gene, which is the first mammalian gene isolated that affects cellular sensitivity to ionizing radiation. The CHO mutant EM9 has 10-fold-higher sensitivity to ethyl methanesulfonate, 1.8 fold-higher sensitivity to ionizing radiation, a reduced capacity to rejoin single-strand DNA breaks, and a 10-fold-elevated level of sister chromatid exchange compared with the CHO parental cells. The complementing human gene was cloned from a cosmid library of a tertiary transformant. Two cosmid clones produced transformants that showed approximately 100% correction of the repair defect in EM9 cells, as determined by the kinetics of strand break repair, cell survival, and the level of sister chromatid exchange. A nearly full-length clone obtained from the pcD2 human cDNA expression library gave approximately 80% correction of EM9, as determined by the level of sister chromatid exchange. Based on an analysis of the nucleotide sequence of the cDNA insert compared with that of the 5' end of the gene from a cosmid clone, the cDNA clone appeared to be missing approximately 100 bp of transcribed sequence, including 26 nucleotides of coding sequence. The cDNA probe detected a single transcript of approximately 2.2 kb in HeLa polyadenylated RNA by Northern (RNA) blot hybridization. From the open reading frame and the positions of likely start sites for transcription and translation, the size of the putative XRCC1 protein is 633 amino acids (69.5 kDa). The size of the XRCC1 gene is 33 kb, as determined by localizing the endpoints on a restriction endonuclease site map of one cosmid clone. The deduced amino acid sequence did not show significant homology with any protein in the protein sequence data bases examined. PMID- 2247055 TI - A 58-base-pair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukin-6. AB - We have cloned the promoter for the human third component of complement (C3) gene and have identified sequences involved in its regulation during the acute-phase response. A construct linking 199 bp of the C3 promoter to the firefly luciferase gene was found to be very responsive to interleukin-1 (IL-1) and modestly responsive to interleukin-6 (IL-6) by transfection analysis in the human hepatoma line Hep3B2. Simultaneous treatment with the two cytokines showed a strong synergy between the actions of the two molecules. A 58-bp fragment (-127 to -70 bp) was shown by 5' and 3' deletional mutagenesis to contain cis-acting elements that mediated both the IL-1 response and the IL-1-plus-IL-6 synergistic response of this promoter. When coupled to a heterologous promoter, this fragment enabled the synergistic induction by IL-1 plus IL-6. Sequences homologous to the palindrome ACATTGCACAATCT, which mediates the induction of the IL-6 gene by IL-1 (S. Akira, H. Isshiki, T. Sugita, O. Tanabe, S. Kinoshita, Y. Nishio, T. Nakajima, T. Hirano, and T. Kishimoto, EMBO J. 9:1897-1906, 1990), and the core sequence of the IL-6-responsive element of the rat alpha 2-macroglobulin gene (CTGGGA; M. Hattori, L. J. Abraham, W. Northemann, and G. H. Fey, Proc. Natl. Acad. Sci. USA 87:2364-2368, 1990) are contained within this fragment in immediate juxtaposition and partially overlapping. Site-directed mutagenesis within this homology region drastically reduced the inducibility of the C3 promoter by either cytokine. DNase I footprinting analysis defined a binding site for the transcription factor CCAAT/enhancer-binding protein (C/EBP), which included the IL-1-responsive element-like sequence. No differences were seen between the footprints generated by using extracts from unstimulated and IL-1 stimulated Hep3B2 cells. However, gel retardation analyses revealed two IL-1 specific bands. The data suggest that the induction by IL-1 is mediated by a factor belonging to the family of C/EBP-related proteins. PMID- 2247056 TI - RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication. AB - Replication of the Chinese hamster dihydrofolate (dhfr) gene initiates near a 281 bp HaeIII fragment of stably bent DNA that binds RIP60, a 60-kDa origin-specific DNA-binding protein that has been purified from HeLa cell nuclear extract (L. Dailey, M. S. Caddle, N. Heintz, and N. H. Heintz, Mol. Cell. Biol. 10:6225-6235, 1990). Circular permutation assays showed that stable DNA bending in the dhfr origin region fragment was due to the presence of five oligo (dA)3-4 tracts, designated bend elements B1 to B5, that are spaced 10 bp apart. DNA bending directed by elements B1 to B5, as assessed by anomolous migration of DNA fragments on polyacrylamide gels, was accentuated at 4 degrees C. Bend element B5, which is in inverse orientation relative to elements B1 to B4, overlaps an ATT-rich motif that comprises the RIP60 protein-binding site. Gel mobility shift assays with circularly permuted bent DNA fragments and purified RIP60 showed that RIP60 markedly enhanced DNA bending of the dhfr origin region sequences. These results suggest that, as in many plasmids, bacteriophages, and eucaryotic viruses, mammalian DNA-binding proteins may enhance DNA bending near origins of replication during initiation of DNA synthesis. PMID- 2247057 TI - Effect of 5' splice site mutations on splicing of the preceding intron. AB - Three exon constructs containing identical intron and exon sequences were mutated at the 5' splice site beginning intron 2 and assayed for the effect of the mutation on splicing of the upstream intron in vitro. Alteration of two or six bases within the 5' splice site reduced removal of intron 1 at least 20-fold, as determined by quantitation of either spliced product or released lariat RNA. The prominent product was skip splicing of exon 1 to exon 3. Examination of complex formation indicated that mutation of the 5' splice site terminating exon 2 depressed the ability of precursor RNAs containing just the affected exon to direct assembly in vitro. These results suggest that mutation at the end of an internal exon inhibits the ability of the exon to be recognized by splicing factors. A comparison of the known vertebrate 5' splice site mutations in which the mutation resides at the end of an internal exon indicated that exon skipping is the preferred phenotype for this type of mutation, in agreement with the in vitro observation reported here. Inhibition of splicing by mutation at the distal and of the exon supports the suggestion that exons, rather than splice sites, are the recognition units for assembly of the spliceosome. PMID- 2247058 TI - Factors involved in specific transcription by mammalian RNA polymerase II: role of transcription factors IIA, IID, and IIB during formation of a transcription competent complex. AB - Human transcription factor TFIID, the TATA-binding protein, was partially purified to a form capable of associating stably with the TATA motif of the adenovirus major late promoter. Binding of the human and yeast TFIID to the TATA motif was stimulated by TFIIA. TFIIA is an integral part of a complex capable of binding other transcription factors. A complex formed with human TFIID and TFIIA (DA complex) was specifically recognized by TFIIB. We found that TFIIB activity was contained in a single polypeptide of 32 kDa and that this polypeptide participated in transcription and was capable of binding to the DA complex to form the DAB complex. Formation of the DAB complex required TFIIA, TFIID, and sequences downstream of the transcriptional start site; however, the DA complex could be formed on an oligonucleotide containing only the adenovirus major late promoter TATA motif. Using anti-TFIIB antibodies and reagents that affect the stability of a transcription-competent complex, we found that yeast and human TFIID yielded DAB complexes with different stabilities. PMID- 2247059 TI - Replication timing of DNA sequences associated with human centromeres and telomeres. AB - The timing of replication of centromere-associated human alpha satellite DNA from chromosomes X, 17, and 7 as well as of human telomeric sequences was determined by using density-labeling methods and fluorescence-activated cell sorting. Alpha satellite sequences replicated late in S phase; however, the alpha satellite sequences of the three chromosomes studied replicated at slightly different times. Human telomeres were found to replicate throughout most of S phase. These results are consistent with a model in which multiple initiations of replication occur at a characteristic time within the alpha satellite repeats of a particular chromosome, while the replication timing of telomeric sequences is determined by either telomeric origins that can initiate at different times during S phase or by replication origins within the flanking chromosomal DNA sequences. PMID- 2247060 TI - Induction of yeast histone genes by stimulation of stationary-phase cells. AB - In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that is unrelated to the mitotic cell cycle. Expression of histone genes, as assessed by Northern (RNA) analysis, was shown to increase promptly after the stimulation, brought about by fresh medium, that activates stationary-phase cells to reenter the mitotic cell cycle. The use of a yeast mutant that is conditionally blocked in the resumption of proliferation at a step that is not part of the mitotic cell cycle (M.A. Drebot, G.C. Johnston, and R.A. Singer, Proc. Natl. Acad. Sci. 84:7948, 1987) showed that this increased gene expression that occurs upon stimulation of stationary-phase cells took place in the absence of DNA synthesis and without the performance of start. This stimulation-specific gene expression was blocked by the mating pheromone alpha-factor, indicating that alpha-factor directly inhibits expression of these histone genes, independently of start. PMID- 2247061 TI - Partial deletion of alpha satellite DNA associated with reduced amounts of the centromere protein CENP-B in a mitotically stable human chromosome rearrangement. AB - A familial, constitutionally rearranged human chromosome 17 is deleted for much of the DNA in its centromeric region but retains full mitotic centromere activity. Fluorescence in situ hybridization, pulsed-field gel electrophoresis, and Southern blot analysis of the residual centromeric region revealed a approximately 700-kb centromeric array of tandemly repeated alpha satellite DNA that was only approximately 20 to 30% as large as a normal array. This deletion was associated with a reduction in the amount of the centromere-specific antigen CENP-B detected by indirect immunofluorescence. The coincidence of the primary constriction, the small residual array of alpha satellite DNA, and the reduced amount of detectable CENP-B support the hypothesis that CENP-B is associated with alpha satellite DNA. Furthermore, the finding that both the deleted chromosome 17 and its derivative supernumerary fragment retained mitotic function and possess centromeric protein antigens suggests that human centromeres are structurally and functionally repetitive. PMID- 2247062 TI - gcr2, a new mutation affecting glycolytic gene expression in Saccharomyces cerevisiae. AB - Screening of a mutagenized strain carrying a multicopy ENO1-'lacZ fusion plasmid revealed a new mutation affecting most glycolytic enzyme activities in a pattern resembling that caused by gcr1: levels in the range of 10% of wild-type levels on glycerol plus lactate but somewhat higher on glucose. The recessive single nuclear gene mutation, named gcr2-1, was unlinked to gcr1, and GCR1 in multiple copies did not restore enzyme levels. GCR2 was obtained by complementation from a YCp50 genomic library; the complemented strain had normal enzyme levels, as did a strain with GCR2 in multiple copies. GCR2 in multiple copies did not suppress gcr1. A chromosomal gcr2 null mutant was constructed; its pattern of enzyme activities resembled that of the gcr2-1 mutant and, like the gcr2-1 mutant, its growth defect on glucose was only partial (in contrast to the glucose negativity of the gcr1 mutant). Northern (RNA) analysis showed that gcr2 and gcr1 affect ENO1 mRNA levels. PMID- 2247063 TI - The SCL gene is formed from a transcriptionally complex locus. AB - We describe the structural organization of the human SCL gene, a helix-loop-helix family member which we believe plays a fundamental role in hematopoietic differentiation. The SCL locus is composed of eight exons distributed over 16 kb. SCL shows a pattern of expression quite restricted to early hematopoietic tissues, although in malignant states expression of the gene may be somewhat extended into later developmental stages. A detailed analysis of the transcript(s) arising from the SCL locus revealed that (i) the 5' noncoding portion of the SCL transcript, which resides within a CpG island, has a complex pattern of alternative exon utilization as well as two distinct transcription initiation sites; (ii) the 5' portions of the SCL transcript contain features that suggest a possible regulatory role for these segments; (iii) the pattern of utilization of the 5' exons is cell lineage dependent; and (iv) all of the currently studied chromosomal aberrations that affect the SCL locus either structurally or functionally eliminate the normal 5' transcription initiation sites. These data suggest that the SCL gene, and specifically its 5' region, may be a target for regulatory interactions during early hematopoietic development. PMID- 2247064 TI - The trypanosome leucine repeat gene in the variant surface glycoprotein expression site encodes a putative metal-binding domain and a region resembling protein-binding domains of yeast, Drosophila, and mammalian proteins. AB - We have identified a new variant surface glycoprotein expression site-associated gene (ESAG) in Trypanosoma brucei, the trypanosome leucine repeat (T-LR) gene. Like most other ESAGs, it is expressed in a life cycle stage-specific manner. The N-terminal 20% of the predicted T-LR protein resembles the metal-binding domains of nucleic acid-binding proteins. The remainder is composed of leucine-rich repeats that are characteristic of protein-binding domains found in a variety of other eucaryote proteins. This is the first report of leucine-rich repeats and potential nucleic acid-binding domains on the same protein. The T-LR gene is adjacent to ESAG 4, which has homology to the catalytic domain of adenylate cyclase. This is intriguing, since yeast adenylate cyclase has a leucine-rich repeat regulatory domain. The leucine-rich repeat and putative metal-binding domains suggest a possible regulatory role that may involve adenylate cyclase activity or nucleic acid binding. PMID- 2247065 TI - The NGFI-B protein, an inducible member of the thyroid/steroid receptor family, is rapidly modified posttranslationally. AB - The NGFI-B gene is rapidly activated by a variety of stimuli that induce cells to differentiate or proliferate. It encodes a protein with a predicted molecular mass of congruent to 61 kDa and is a member of the thyroid/steroid hormone receptor gene family. To characterize this protein, monoclonal antibodies were raised against a bacterial TrpE-NGFI-B fusion protein that encompasses a large portion (Glu-410 to Leu-527) of the carboxy-terminal domain of NGFI-B. These antibodies detected a protein that was rapidly synthesized in response to nerve growth factor (NGF) and migrated as a broad band on sodium dodecyl sulfate polyacrylamide gels with an apparent molecular mass that ranged from 63 to 88 kDa. Pulse-chase analysis demonstrated that NGFI-B was rapidly posttranslationally modified and was a short-lived protein. NGFI-B was found to be a phosphorylated protein, and the multiple NGFI-B species coalesced into a single, more rapidly migrating species when treated with alkaline phosphatase. PC12 cells grown in the absence of NGF contained low levels of NGFI-B that was underphosphorylated. Epidermal growth factor, phorbol ester, and the calcium ionophore A23187 stimulated the synthesis of NGFI-B that was composed largely of underphosphorylated, rapidly migrating species. In contrast, basic fibroblast growth factor, which promotes differentiation of PC12 cells, induced the synthesis of NGFI-B species similar to those synthesized in response to NGF treatment. The underphosphorylated NGFI-B found in uninduced PC12 cells was found only in the nucleus, whereas NGFI-B in NGF-stimulated PC12 cells was present in approximately equal quantities in the cytoplasm and nucleus. Consistent with the cellular distribution observed in nonstimulated PC12 cells, the highly phosphorylated species were predominantly cytoplasmic whereas the more rapidly migrating forms were nuclear. PMID- 2247066 TI - A DNA-activated protein kinase from HeLa cell nuclei. AB - A DNA-activated protein kinase (DNA-PK) was purified from nuclei of HeLa cells. Activity was associated with a single high-molecular-mass (approximately-300,000 Da) polypeptide when analyzed by gel filtration, denaturing polyacrylamide gel electrophoresis, and Western immunoblotting using a monoclonal antibody that also inhibits enzyme activity. Nuclear localization was indicated by subcellular fractionation and confirmed by immunofluorescence on whole cells. Double-stranded DNA stimulated phosphorylation of the 300-kDa polypeptide in purified preparations as well as phosphorylation of the exogenous substrates alpha-casein, simian virus 40 large T antigen, and the human heat shock protein hsp90. Autophosphorylation led to inactivation of the enzyme. The phosphorylation of casein was stimulated over 30-fold by DNA and was specific for serine and threonine residues. Bovine serum albumin and histone H1 were poor substrates for DNA-PK, and no phosphorylation of immunoglobulin G or histones other than H1 was observed. Supercoiled or heat-denatured DNA and synthetic double-stranded RNA or RNA-DNA copolymers did not stimulate casein phosphorylation by DNA-PK. Interaction of the enzyme with DNA in the absence of exogenous substrates was demonstrated by thermal inactivation and gel mobility shifts. These characteristics identify DNA-PK as distinct from other protein kinases described in the literature and suggest that activation by DNA is an important feature of the enzyme's in vivo function. PMID- 2247067 TI - Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen. AB - HeLa cells contain a serine/threonine protein kinase (DNA-PK) that is strongly activated in vitro by low concentrations of double-stranded DNA (dsDNA). Activation was specific for dsDNA; both natural DNAs and synthetic oligonucleotides functioned as kinase activators. The fact that DNA-PK activity was rapidly inhibited by incubation with dsDNA and ATP suggests that DNA-PK activity also may be regulated by autophosphorylation. During gel filtration, DNA PK activity behaved as a 350-kDa protein, and highly purified DNA-PK contained a dsDNA-binding, 350-kDa polypeptide that was phosphorylated in a dsDNA-dependent manner. We conclude that this 350-kDa polypeptide is likely to be DNA-PK. Previously we showed that the dsDNA-activated kinase phosphorylates two threonines at the N terminus of hsp90 alpha (S. P. Lees-Miller and C. W. Anderson, J. Biol. Chem. 264:17275-17280, 1989). Here we show that DNA-PK also phosphorylates the simian virus 40 large tumor antigen, the mouse tumor suppressor protein p53, the human Ku autoantigen, and two unidentified HeLa DNA associated polypeptides of 52 and 110 kDa. Identification of these and other newly identified DNA-binding substrates suggest that the dsDNA-activated kinase may regulate transcription, DNA replication, or cell growth. PMID- 2247068 TI - Regulation of glucose transporters in LLC-PK1 cells: effects of D-glucose and monosaccharides. AB - Regulation of D-glucose transport in the porcine kidney epithelial cell line LLC PK1 was examined. To identify the sodium-coupled glucose transporter (SGLT), we cloned and sequenced several partial cDNAs homologous to SGLT1 from rabbit small intestine (M. A. Hediger, M. J. Coady, T. S. Ikeda, and E. M. Wright, Nature (London) 330:379-381, 1987). The extensive homology of the two sequences leads us to suggest that the high-affinity SGLT expressed by LLC-PK1 cells is SGLT1. SGLT1 mRNA levels were highest when the D-glucose concentration in the culture medium was 5 to 10 mM. Addition of D-mannose or D-fructose, but not D-galactose, in the presence of 5 mM D-glucose suppressed SGLT1 mRNA levels. SGLT1 activity, measured by methyl alpha-D-glucopyranoside uptake, paralleled message levels except in cultures containing D-galactose. Therefore, SGLT1 gene expression may respond either to the cellular energy status or to the concentration of a hexose metabolite(s). By isolating several cDNAs homologous to rat GLUT-1, we identified the facilitated glucose transporter in LLC-PK1 cells as the erythroid/brain type GLUT-1. High-stringency hybridization of a single mRNA transcript to the rat GLUT 1 cDNA probe and failure to observe additional transcripts hybridizing either to GLUT-1 or to GLUT-2 probes at low stringency provide evidence that GLUT-1 is the major facilitated glucose transporter in this cell line. LLC-PK1 GLUT-1 mRNAs were highest at medium D-glucose concentrations of less than or equal to 2 mM. D Fructose, D-mannose, and to a lesser extent D-galactose all suppressed GLUT-1 mRNA levels. Since the pattern of SGLT1 and GLUT-1 expression differed, particularly in low D-glucose or in the presence of D-galactose, we suggest that the two transporters are regulated independently. PMID- 2247069 TI - Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae. AB - The TUP1 and CYC8 (= SSN6) genes of Saccharomyces cerevisiae play a major role in glucose repression. Mutations in either TUP1 or CYC8 eliminate or reduce glucose repression of many repressible genes and induce other phenotypes, including flocculence, failure to sporulate, and sterility of MAT alpha cells. The TUP1 gene was isolated in a screen for genes that regulate mating type (V.L. MacKay, Methods Enzymol. 101:325-343, 1983). We found that a 3.5-kb restriction fragment was sufficient for complete complementation of tup1-100. The gene was further localized by insertional mutagenesis and RNA mapping. Sequence analysis of 2.9 kb of DNA including TUP1 revealed only one long open reading frame which predicts a protein of molecular weight 78,221. The predicted protein is rich in serine, threonine, and glutamine. In the carboxyl region there are six repeats of a pattern of about 43 amino acids. This same pattern of conserved residues is seen in the beta subunit of transducin and the yeast CDC4 gene product. Insertion and deletion mutants are viable, with the same range of phenotypes as for point mutants. Deletions of the 3' end of the coding region produced the same mutant phenotypes as did total deletions, suggesting that the C terminus is critical for TUP1 function. Strains with deletions in both the CYC8 and TUP1 genes are viable, with phenotypes similar to those of strains with a single deletion. A deletion mutation of TUP1 was able to suppress the snf1 mutation block on expression of the SUC2 gene encoding invertase. PMID- 2247070 TI - Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication. AB - NIH 3T3 cells infected with Moloney murine leukemia virus (MoMLV) express high levels of virus-specific RNA. To inhibit replication of the virus, we stably introduced chimeric tRNA genes encoding antisense templates into NIH 3T3 cells via a retroviral vector. Efficient expression of hybrid tRNA-MoMLV antisense transcripts and inhibition of MoMLV replication were dependent on the use of a particular type of retroviral vector, the double-copy vector, in which the chimeric tRNA gene was inserted in the 3' long terminal repeat. MoMLV replication was inhibited up to 97% in cells expressing antisense RNA corresponding to the gag gene and less than twofold in cells expressing antisense RNA corresponding to the pol gene. RNA and protein analyses suggest that inhibition was exerted at the level of translation. These results suggest that RNA polymerase III-based antisense inhibition systems can be used to inhibit highly expressed viral genes and render cells resistant to viral replication via intracellular immunization strategies. PMID- 2247071 TI - Identification of cis-acting regulatory elements in the promoter region of the rat brain creatine kinase gene. AB - The functional organization of the rat brain creatine kinase (ckb) promoter was analyzed by deletion, linker scanning, and substitution mutagenesis. Mutations were introduced into the ckb promoter of hybrid ckb/neo (neomycin resistance gene) genes, and the mutant genes were expressed transiently in HeLa cells. Expression was assayed by primer extension analysis of neo RNA, which allowed the transcription start sites and the amount of transcription to be determined. Transfections and primer extension reactions were internally controlled by simultaneous analysis of transcription from the adenovirus VA gene located on the same plasmid as the hybrid ckb/neo gene. We demonstrate that 195 bp of the ckb promoter is sufficient for efficient in vivo expression in HeLa cells. A nonconsensus TTAA element at -28 bp appears to provide the TATA box function for the ckb promoter in vivo. Two CCAAT elements, one at -84 bp and the other at -54 bp, and a TATAAA TA element (a consensus TATA box sequence) at -66 bp are required for efficient transcription from the TTAA element. In addition, we present evidence that the consensus beta-globin TATA box responds to the TATAAATA element in the same way as the ckb nonconsensus TTAA element. PMID- 2247073 TI - Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage. AB - In eucaryotic cells, incompletely replicated or damaged chromosomes induce cell cycle arrest in G2 before mitosis, and in the yeast Saccharomyces cerevisiae the RAD9 gene is essential for the cell cycle arrest (T.A. Weinert and L. H. Hartwell, Science 241:317-322, 1988). In this report, we extend the analysis of RAD9-dependent cell cycle control. We found that both induction of RAD9-dependent arrest in G2 and recovery from arrest could occur in the presence of the protein synthesis inhibitor cycloheximide, showing that the mechanism of RAD9-dependent control involves a posttranslational mechanism(s). We have isolated and determined the DNA sequence of the RAD9 gene, confirming the DNA sequence reported previously (R. H. Schiestl, P. Reynolds, S. Prakash, and L. Prakash, Mol. Cell. Biol. 9:1882-1886, 1989). The predicted protein sequence for the Rad9 protein bears no similarity to sequences of known proteins. We also found that synthesis of the RAD9 transcript in the cell cycle was constitutive and not induced by X-irradiation. We constructed yeast cells containing a complete deletion of the RAD9 gene; the rad9 null mutants were viable, sensitive to X- and UV irradiation, and defective for cell cycle arrest after DNA damage. Although Rad+ and rad9 delta cells had similar growth rates and cell cycle kinetics in unirradiated cells, the spontaneous rate of chromosome loss (in unirradiated cells) was elevated 7- to 21-fold in rad9 delta cells. These studies show that in the presence of induced or endogenous DNA damage, RAD9 is a negative regulator that inhibits progression from G2 in order to preserve cell viability and to maintain the fidelity of chromosome transmission. PMID- 2247072 TI - Sequence and functional similarity between a yeast ribosomal protein and the Escherichia coli S5 ram protein. AB - The accurate and efficient translation of proteins is of fundamental importance to both bacteria and higher organisms. Most of our knowledge about the control of translational fidelity comes from studies of Escherichia coli. In particular, ram (ribosomal ambiguity) mutations in structural genes of E. coli ribosomal proteins S4 and S5 have been shown to increase translational error frequencies. We describe the first sequence of a ribosomal protein gene that affects translational ambiguity in a eucaryote. We show that the yeast omnipotent suppressor SUP44 encodes the yeast ribosomal protein S4. The gene exists as a single copy without an intron. The SUP44 protein is 26% identical (54% similar) to the well-characterized E. coli S5 ram protein. SUP44 is also 59% identical (78% similar) to mouse protein LLrep3, whose function was previously unknown (D.L. Heller, K.M. Gianda, and L. Leinwand, Mol. Cell. Biol. 8:2797-2803, 1988). The SUP44 suppressor mutation occurs near a region of the protein that corresponds to the known positions of alterations in E. coli S5 ram mutations. This is the first ribosomal protein whose function and sequence have been shown to be conserved between procaryotes and eucaryotes. PMID- 2247074 TI - Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis. AB - The basic carboxy terminus of p53 plays an important role in directing the protein into the nuclear compartment. The C terminus of the p53 molecule contains a cluster of several nuclear localization signals (NLSs) that mediate the migration of the protein into the cell nucleus. NLSI, the most active domain, is highly conserved in genetically diverged species and shares perfect homology with consensus NLS sequences found in other nuclear proteins. The other two NLSs, II and III, appear to be less effective and less conserved. Although nuclear localization is dictated primarily by the NLSs inherent in the primary amino acid sequence, the actual nuclear homing can be modified by interactions with other proteins expressed in the cell. Comparison between wild-type p53 and naturally occurring mutant p53 showed that both protein categories could migrate into the nucleus of rat primary embryonic fibroblasts by essentially similar mechanisms. Nuclear localization of both proteins was totally dependent on the existence of functional NLS domains. In COS cells, however, we found that NLS-deprived wild type p53 molecules could migrate into the nucleus by complexing with another nuclear protein, simian virus 40 large-T antigen. Wild-type and mutant p53 proteins differentially complexed with viral or cellular proteins, which may significantly affect the ultimate compartmentalization of p53 in the cell; this finding suggests that the actual subcellular compartmentalization of proteins may differ in various cell type milieux and may largely be affected by the ability of these proteins to complex with other proteins expressed in the cell. Experiments designed to test the physiological significance of p53 subcellular localization indicated that nuclear localization of mutant p53 is essential for this protein to enhance the process of malignant transformation of partially transformed cells, suggesting that p53 functions within the cell nucleus. PMID- 2247075 TI - Mechanism of estrogen receptor-dependent transcription in a cell-free system. AB - RNA synthesis was stimulated directly in a cell-free expression system by crude preparations of recombinant mouse estrogen receptor (ER). Receptor-stimulated transcription required the presence of estrogen response elements (EREs) in the test template and could be specifically inhibited by addition of competitor oligonucleotides containing EREs. Moreover, polyclonal antibodies directed against the DNA-binding region of ER inhibited ER-dependent transcription. In our cell-free expression system, hormone-free ER induced transcription in a hormone independent manner. Evidence is presented suggesting that ER acts by facilitating the formation of a stable preinitiation complex at the target gene promoter and thus augments the initiation of transcription by RNA polymerase II. These observations lend support to our current understanding of the mechanism of steroid receptor-regulated gene expression and suggest strong conservation of function among members of the steroid receptor superfamily. PMID- 2247076 TI - Two adjacent C/EBP-binding sequences that participate in the cell-specific expression of the mouse serum amyloid A3 gene. AB - Serum amyloid A (SAA) is a major acute-phase protein synthesized primarily in the liver. Its expression, very low in normal animals, is increased several hundredfold following acute inflammation. To examine DNA sequences involved in liver-specific expression, 5'-flanking regions of the mouse SAA3 gene were analyzed by transient transfection, band shift, and DNase I protection assays. We found that a 56-bp fragment immediately 5' to the TATA box spanning the region 93 to -38 relative to the transcription start site was sufficient to confer liver cell-specific transcriptional activation onto a heterologous promoter in a dose dependent and orientation-independent manner. This DNA fragment could form DNA protein complexes with heat-stable nuclear proteins, and the complexes formed could be specifically competed for by excess oligomers corresponding to the C/EBP or DBP-binding sites but not by binding sites for three other liver-specific factors, HNF1, HNF3, and HNF4. Footprint analysis using Hep3B nuclear extracts revealed two adjacent footprint regions within this 56-bp fragment, the distal region having at least fivefold-greater affinity than the proximal region. Identical footprint patterns were observed when purified recombinant C/EBP protein was used. These results indicated that binding of C/EBP to this 56-bp fragment plays an important role in vivo in enhancing expression of the mouse SAA3 gene in hepatocytes. PMID- 2247078 TI - Activation of chromosomal vitellogenin genes in Xenopus oocytes by pure estrogen receptor and independent activation of albumin genes. AB - We generate pure estrogen receptor protein in Xenopus oocytes by injecting them with estrogen receptor mRNA synthesized in vitro. A chromosomal vitellogenin gene, which normally responds to estrogen only in liver cells, is activated. Primer extension shows that initiation is accurate, and ribonuclease mapping shows that the first exon is correctly spliced out of the initial transcript. Long transcripts are produced, one being equal in length to poly(A)- vitellogenin mRNA. Immunochemical estimates of receptor levels in the oocyte nuclei suggest that pure receptor, acting alone, cannot activate oocyte vitellogenin genes unless unusually large amounts are present. However, when a receptor-free extract from liver cells is also injected, the amount of receptor required is reduced. Such an extract, but not pure receptor, can also activate albumin genes in oocytes. PMID- 2247077 TI - Transcriptional initiation is controlled by upstream GC-box interactions in a TATAA-less promoter. AB - Numerous genes contain TATAA-less promoters, and the control of transcriptional initiation in this important promoter class is not understood. We have determined that protein-DNA interactions at three of the four proximal GC box sequence elements in one such promoter, that of the hamster dihydrofolate reductase gene, control initiation and relative use of the major and minor start sites. Our results indicate that although the GC boxes are apparently equivalent with respect to factor binding, they are not equivalent with respect to function. At least two properly positioned GC boxes were required for initiation of transcription. Abolishment of DNA-protein interaction by site-specific mutation of the most proximal GC box (box I) resulted in a fivefold decrease in transcription from the major initiation site and a threefold increase in heterogeneous transcripts initiating from the vicinity of the minor start site in vitro and in vivo. Mutations that separately abolished interactions at GC boxes II and III while leaving GC box I intact affected the relative utilization of both the major and minor initiation sites as well as transcriptional efficiency of the promoter template in in vitro transcription and transient expression assays. Interaction at GC box IV when the three proximal boxes were in a wild type configuration had no effect on transcription of the dihydrofolate reductase gene promoter. Thus, GC box interactions not only are required for efficient transcription but also regulate start site utilization in this TATAA-less promoter. PMID- 2247079 TI - A cloned human CCAAT-box-binding factor stimulates transcription from the human hsp70 promoter. AB - The basal promoter of the human hsp70 gene is predominantly controlled by a CCAAT element at position -70 relative to the transcriptional initiation site. We report the isolation of a novel cDNA clone encoding a 114-kDa polypeptide that binds to the CCAAT element of the hsp70 promoter. Expression of this CCAAT binding factor (CBF) cDNA activated transcription from cotransfected hsp70 promoter-reporter gene constructs in a CCAAT-dependent manner. CCAAT-binding factor shows no homology to the previously identified human CCAAT transcription factor or rat CCAAT/enhancer-binding protein. PMID- 2247080 TI - Activation of a late H2B histone gene in blastula-stage sea urchin embryos by an unusual enhancer element located 3' of the gene. AB - In the sea urchin embryo, late histone genes are transcribed at low levels during cleavage and blastula formation and at substantially higher levels in later stages of embryogenesis. To investigate the molecular basis of the stage-specific expression of a late H2B histone gene, we injected mutant genes lacking portions of 5'- and 3'-flanking regions into Lytechinus pictus embryos and monitored their expression by RNase protection. A 200-bp region located 489 bp downstream of the mRNA 3' terminus was necessary for the increase in transcription of the late H2B gene at the mid-blastula stage of development. DNase I and methylation interference footprint analyses located only one factor-binding site in this region, and gel mobility shift experiments showed that the DNA-binding activity of this factor (designated H2B abp 1) paralleled the transcriptional activity of the L1 H2B gene. Additional mutagenesis and microinjection experiments located the activator element to a 32-bp DNA segment that includes the H2B abp 1-binding site. These experiments also showed that the 32-bp fragment functions independently of position and orientation and therefore has the hallmarks of an enhancer. That this fragment contains most or all of the L1 H2B gene transcription-stimulatory activity makes it unusual among enhancerlike elements, which generally consist of several clustered factor-binding sites that act additively or cooperatively to affect transcription. The nucleotide sequence of the L1 H2B enhancer element suggests that the trans-acting factor that interacts with it is a member of the antennapedia or engrailed class of homeodomain proteins. PMID- 2247081 TI - Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae. AB - VPS34 gene function is required for the efficient localization of a variety of vacuolar proteins. We have cloned and sequenced the wild-type VPS34 gene in order to gain a better understanding of the role of its protein product in this intracellular sorting pathway. Interestingly, disruption of the VPS34 locus resulted in a temperature-sensitive growth defect, indicating that the VPS34 gene is essential for vegetative growth only at elevated growth temperatures. As with the original vps34 alleles, vps34 null mutants exhibited severe vacuolar protein sorting defects and possessed a morphologically normal vacuolar structure. The VPS34 gene DNA sequence identifies an open reading frame that could encode a hydrophilic protein of 875 amino acids. The predicted protein sequence lacks any apparent signal sequence or membrane-spanning domains, suggesting that Vps34p does not enter the secretory pathway. Results from immunoprecipitation experiments with antiserum prepared against a TrpE-Vps34 fusion protein were consistent with this prediction: a rare, unglycosylated protein of approximately 95,000 Da was detected in extracts of wild-type Saccharomyces cerevisiae cells. Cell fractionation studies indicated that a significant portion of the Vps34p is found associated with a particulate fraction of yeast cells. This particulate Vps34p was readily solubilized by treatment with 2 M urea but not with Triton X 100, suggesting that the presence of Vps34p in this pelletable structure is mediated by protein-protein interactions. vp34 mutant cells also exhibited a defect in the normal partitioning of the vacuolar compartment between mother and daughter cells during cell division. In more than 80% of the delta vps34 dividing cells examined, no vacuolar structures were observed in the newly emerging bud, whereas in wild-type dividing cells, more than 95% of the buds had a detectable vacuolar compartment. Our results suggest that the Vps34p may act as a component of a relatively large intracellular structure that functions to facilitate specific steps of the vacuolar protein delivery and inheritance pathways. PMID- 2247082 TI - Aryl hydrocarbon induction of rat cytochrome P-450d results from increased precursor RNA processing. AB - We have previously demonstrated that cytochrome P-450d mRNA accumulation is induced at a posttranscriptional level by 3-methylcholanthrene (MCA) in primary cultures of rat hepatocytes grown in serum-free hormonally defined medium. Using dactinomycin chase experiments in this culture system, we found that MCA had no effect on the P-450d mRNA half-life. In addition, induction of P-450d occurred both in the presence and in the absence of protein synthesis inhibitors. An analysis of nuclear precursors showed that the accumulation of the primary transcript of the P-450d gene was induced to the same extent as that of the mature mRNA after MCA treatment and that the pattern of accumulation of precursors differed between treated and control liver cells. Since P-450d induction is thought to be a receptor-mediated event, these data are consistent with a model in which a direct interaction occurs between the receptor-ligand complex and the primary transcript. PMID- 2247083 TI - Pip92: a short-lived, growth factor-inducible protein in BALB/c 3T3 and PC12 cells. AB - pip92 is a cellular immediate-early gene inducible by serum growth factors in fibroblasts. It is also induced in the rat pheochromocytoma cell line PC12 by agents that cause proliferation, neuronal differentiation, and membrane depolarization. We show that the pip92-encoded polypeptide is a proline-rich protein of 221 amino acids, has an extremely short half-life, and is localized in the cytoplasm. We hypothesize that Pip92 plays a role in mediating the cellular responses to a variety of extracellular signals. PMID- 2247084 TI - Increased rate of base substitution in a hamster mutator strain obtained during serial selection for gene amplification. AB - The pattern of mutations produced by a mutator gene (obtained during serial selection for amplification of the dihydrofolate reductase [dhfr] locus) shows a pronounced shift from that found in wild-type cells. The rate of certain types of base substitutions (particularly transitions) is dramatically increased, while gene rearrangements constitute a lower proportion of mutations. These data suggest a lower fidelity of the replication process in the mutator strain. PMID- 2247085 TI - The PRE and PQ box are functionally distinct yeast pheromone response elements. AB - Saccharomyces cerevisiae mating pheromones function by binding to cell surface receptors and activating signal transduction processes which regulate gene expression. In this report, we have analyzed the minimum sequence requirements for conferring both a and alpha mating pheromone inducibilities onto a heterologous promoter. Here we show that the repetitive pheromone response element (PRE) which binds to STE12 protein is sufficient to confer pheromone responsiveness only when present in multiple copies. Moreover, by itself, it is preferentially responsive to alpha factor in a cells. In contrast, a single copy of the PQ box of the STE3 upstream activation sequence (UAS) is sufficient to confer a-factor responsiveness in alpha cells. The PQ box binds both MCM1 and MAT alpha 1 in a cooperative manner, and neither the P nor Q site alone is sufficient to confer a-factor responsiveness. In a cells, however, even multiple copies of the PQ box fail to confer alpha-factor responsiveness. Therefore, the PRE and the PQ box are functionally distinct pheromone-responsive elements with opposite cell type specificities. Moreover, these results indicate that the MCM1 protein functions in a signal transduction pathway in a manner analogous to that of its mammalian homolog, the serum response factor, which regulates the expression of the c-fos proto-oncogene in mammals. PMID- 2247087 TI - The glycopeptides of the mouse immunoglobulin A T15. AB - Cleavage of mouse IgA T15 with papain yielded (a) a glycosylated Fab fragment, (b) a non-glycosylated Fc fragment and (c) a glycosylated C-terminal peptide. The cleavage sites at the hinge and at the end of the C alpha 3 domain were located by sequencing. The two glycopeptides were prepared from the Fab and C-terminal fragments by pronase digestion. The C alpha 1 glycopeptide at Asn 155 was complex type with alpha (1-3)galactose terminal groups, and closely resembled the Asn 171 glycopeptide of mouse IgM (Anderson et al. (1985) Arch. Biochem. Biophys. 243, 605-618). In contrast, the C-terminal glycopeptide at Asn 446 was entirely different from the corresponding IgM glycopeptide, being complex rather than high mannose type. PMID- 2247086 TI - Species-specific lens activation of the thymidine kinase promoter by a single copy of the mouse alpha A-CRYBP1 site and loss of tissue specificity by multimerization. AB - One copy of the mouse alpha A-crystallin gene alpha A-CRYBP1 site activated the thymidine kinase (tk) promoter in a mouse lens epithelial cell line but not in primary chicken lens cells; multiple copies further activated the tk promoter and extended expression to fibroblasts, B cells, and chicken lens cultures. The loss of lens specificity by multimerization may place selective constraints on the number of alpha A-CRYBP1 sites in the alpha A-crystallin promoter. PMID- 2247089 TI - Inhibition of in vitro transcription by adenosine antibodies. AB - Antibodies against adenosine markedly inhibited in vitro transcription in isolated BHK 21 nuclei in a dose-dependent manner. The inhibition was specific as it could be completely reversed by the addition of homologous hapten. Addition of RNA at low concentration reversed the inhibition, whereas excess DNA did not have any effect. Adenosine antibodies also inhibited in vitro transcription with calf thymus DNA and E. coli RNA polymerase. Antibodies that react with DNA but not with RNA such as anti-dpA, anti-dpC and anti-DNA failed to inhibit in vitro transcription in isolated nuclei as well as with calf thymus DNA and E. coli RNA polymerase. The results strongly indicate that the binding of adenosine antibodies to RNA is responsible for the inhibition of transcription. PMID- 2247088 TI - Cloning and expression of a lymphocyte activation gene (LAG-1). AB - Using subtractive hybridization of a cDNA library we have identified a human gene, termed LAG-1 (for "Lymphocyte Activation Gene-1"). This cDNA codes for a 69 amino-acid polypeptide which belongs to a new class of recently described proteins secreted by activated lymphocytes and/or monocytes. The LAG-1 gene was cloned, sequenced and its chromosomal location assigned to chromosome 17 (q21 band). The promoter region of the LAG-1 gene was shown to include a GM-CSF-like decanucleotide sequence. Using a baculovirus vector expression system, we found that a 10 kDa recombinant LAG-1 protein is secreted by AcNPV infected SF9 cells, as determined in Western blot experiments by the reactivity of specific anti peptidic heteroantibodies. Finally the natural LAG-1 protein was precipitated from the supernatant of internally labeled activated Nk cells and shown to migrate as a single entity of 14 kDa in SDS-PAGE analysis. PMID- 2247090 TI - Cloning of a cDNA for a T cell produced molecule with a putative immune regulatory role. AB - An expression cDNA library was constructed from the helper T cell hybridoma, A.1.1, which has been shown to produce constitutively proteins involved in the down regulation of the immune response. From this library we identified and characterized a cDNA clone, J6B7, by screening with a polyclonal antibody specific for secreted immune regulatory proteins. The mRNA for J6B7 is expressed specifically in some T cells, but not in the thymoma BW5147 or liver cells. J6B7 is 2937 nucleotides in length and contains one open reading frame encoding for a peptide of predicted Mr of 98,042. The nucleotide and deduced amino acid sequences of J6B7 did not reveal significant homology to any published sequences. Hybridization and translation experiments reveal that the J6B7 can hybrid select mRNA from total RNA isolated from either A.1.1 cells or thymic tissue which can be translated in vitro to a peptide which is bound by a monoclonal antibody (mAb) specific for antigenic determinant(s) shared by immune regulatory proteins. Furthermore, the in vitro translated proteins obtained from A.1.1 cells and thymus showed significant suppression of a mixed lymphocyte reaction (MLR) in a dose dependent manner, reaching maximum suppression of 71% and 89%, respectively. These results suggest that the cDNA, J6B7, codes for an immune regulatory protein. PMID- 2247091 TI - The mechanism of activation of the alternative pathway of complement by cell bound C4b. AB - Investigations into the mechanism of alternative pathway-dependent lysis of C4b coated cells are reported. Test cells (EAC1q4b) were formed by reaction of sheep erythrocytes with antibody, C1 and C4. In C5-deficient serum, more C3b was deposited onto EAC1qC4b than onto control cells (EAC1q). The possibility that the C4bBb enzyme could form was considered, but no C3 convertase activity was generated when magnesium, properdin and factors B and D were added to EAC1qC4b. Binding studies employing radiolabeled components provided evidence that C4b bound the C3 convertase, C3bBbP, through a weak interaction with C3b. These data implied C3 conversion would be localized to the cell surface, thereby amplifying C3b deposition. This could be demonstrated in vitro. C3b, properdin, factor B and factor D were all required and the amplified C3b deposition was not due to deposition onto C4b itself. In serum, C5 convertase activity would be consequently expressed and cell lysis would result. This could be the mechanism by which the sera of C2-deficient patients mediate lysis of antibody coated sheep erythrocytes. PMID- 2247092 TI - [The course of psychiatric diseases in the population]. PMID- 2247093 TI - Early stage breast cancer. AB - The National Institutes of Health Consensus Development Conference on Treatment of Early-Stage Breast Cancer brought together surgical, radiation, and medical oncologists, biostatisticians, psychologists, nurses, and other health care professionals as well as the public to address: the roles of mastectomy versus breast conservation, the role of adjuvant therapy, and the use of prognostic indicators in the treatment and management of early-stage breast cancer. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) breast conservation treatment is an appropriate method of primary therapy for the majority of women with Stage I and II breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast; (2) the majority of patients with node negative breast cancer are cured by surgery or by surgery and radiation without further therapy; (3) there is clear evidence that the rate of local and distant recurrence is decreased by both adjuvant combination cytotoxic chemotherapy and by adjuvant tamoxifen; (4) the decision to use adjuvant treatment should follow a thorough discussion with the patient regarding the possible risks and toxicities of therapy and its impact on quality of life; (5) and patients with tumors less than or equal to 1 centimeter have an excellent prognosis and do not require adjuvant therapy outside of clinical trials. The full text of the consensus panel's statement follows. PMID- 2247094 TI - Syphilis: from Beethoven to HIV. PMID- 2247095 TI - Chlamydia. PMID- 2247096 TI - Mycobacterial infection in the AIDS era: implications for infection control and employee health. PMID- 2247097 TI - Pulmonary infection with Mycobacterium avium-intracellulare: diagnosis, clinical patterns, treatment. AB - Most physicians fail to recognize Mycobacterium avium-intracellulare (MAI) as a major pathogen for pulmonary disease among patients admitted to hospitals throughout the United States. In a review of all records of positive MAI cultures during the 10 years beginning July 1, 1979, at The Mount Sinai Hospital, New York City, we have identified 244 patients who had pulmonary disease primarily or secondarily complicated by MAI. We also identified another 243 patients as false positive for MAI infection. We classed as false positives patients who had no subsequent positive culture and whose clinical picture was and remained incompatible with MAI infection. We identified four distinct clinical patterns in the 244 patients with true positive MAI infections: (a) pulmonary nodules ("tuberculomas") indistinguishable from pulmonary neoplasms (78 patients); (b) chronic bronchitis or bronchiectasis with sputum repeatedly positive for MAI or granulomas on biopsy (58 patients, virtually all older white women); (c) cavitary lung disease and scattered pulmonary nodules mimicking M. tuberculosis infection (12 patients); (d) diffuse pulmonary infiltrations in immunocompromised hosts, primarily patients with AIDS (96 patients). The diagnosis should be established either by surgical resection and culture of resected nodules, or by three repeated positive acid-fast bacillus cultures of sputum or fluid and tissue obtained by bronchoscopy, or by biopsy of other tissue which shows granulomas and one or more positive MAI cultures. Surgical resection is the best treatment for "solitary" MAI nodules. Multiple antituberculous drug therapy is indicated for patients with chronic infection that impairs function or causes hemoptysis. The presence of MAI in the sputum or lung aspirates of patients with AIDS usually heralds the presence of a preterminal disseminated infection. PMID- 2247098 TI - HIV infection in healthcare workers: risk and prevention. AB - Patients with HIV infection pose a minimal but real risk to healthcare providers who sustain an exposure to such patients' blood or body fluids. Using data from large prospective studies, the estimated risk following parenteral exposure to HIV-positive blood is 0.4%. When a healthcare worker sustains an exposure, Mount Sinai Infection Control recommends immediate referral of the worker to an employee health service or emergency room for evaluation of the incident. Appropriate prophylaxis for hepatitis should be administered in a timely fashion. Counseling should be provided to exposed healthcare workers on the risk for HIV infection and precautions to take in the followup period. Zidovudine should be offered in a timely fashion as well; however, the ultimate decision on that treatment rests with the person exposed. PMID- 2247099 TI - Resurgence of tuberculosis: relationship to HIV infection and implications for infection control. PMID- 2247100 TI - Influenza: a serious epidemic disease that can be prevented. PMID- 2247101 TI - Endocrinologic and metabolic manifestations of the acquired immunodeficiency syndrome. AB - The endocrine abnormalities associated with acquired immunodeficiency syndrome (AIDS) are reviewed. These include adrenal insufficiency, hyporeninemic hypoaldosteronism, panhypopituitarism, hypogonadism, and alterations in thyroid function tests. AIDS-related infections or neoplasms may lead to hypercalcemia, whereas malabsorption may cause hypocalcemia. The possibility that AIDS associated cachexia and hypertriglyceridemia may be caused by cachectin (tumor necrosis factor) is discussed, along with possible therapy for cachexia with megestrol acetate. Ketoconazole, sulfonamides, and pentamidine have specific, potentially deleterious metabolic effects when used in AIDS patients. Because treatment of endocrinological abnormalities of AIDS is often effective, improved diagnosis and appropriate therapy of these abnormalities will result in improved quality of life and, possibly, longer survival of patients with AIDS. PMID- 2247103 TI - Research Day in Medicine 1990. September 17, 1990. Abstracts. PMID- 2247102 TI - Tailgut cyst (retrorectal cyst hamartoma): case report and review. PMID- 2247104 TI - A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome. AB - BACKGROUND: Candida albicans infection has been proposed to cause a chronic hypersensitivity syndrome characterized by fatigue, premenstrual tension, gastrointestinal symptoms, and depression. Long-term antifungal therapy has been advocated as treatment for the syndrome, which is most often diagnosed in women with persistent or recurrent candida vaginitis. METHODS: To determine the efficacy of nystatin therapy for presumed candidiasis hypersensitivity syndrome, we conducted a 32-week randomized, double-blind, cross-over study using four different combinations of nystatin or placebo given orally or vaginally in 42 premenopausal women who met present criteria for the syndrome and had a history of candida vaginitis. The outcomes studied were the changes from base line in scores for vaginal, systemic, and overall symptoms and in the results of standardized psychological tests. RESULTS: The three active-treatment regimens (oral and vaginal nystatin, oral nystatin and vaginal placebo, and oral placebo and vaginal nystatin) and the all-placebo regimen significantly reduced both vaginal and systemic symptoms (P less than 0.001), but nystatin did not reduce the systemic symptoms significantly more than placebo. On average, the scores for systemic symptoms improved 25 percent with the three active-treatment regimens and 23 percent with the all-placebo regimen, a difference of only 2 percent (95 percent confidence interval, -3 to 7 percent). As expected, the three active treatment regimens were more effective than placebo in relieving vaginal symptoms (P less than 0.001). All four regimens reduced psychological symptoms and global indexes of distress; there were no significant differences among the treatment regimens. CONCLUSIONS: In women with presumed candidiasis hypersensitivity syndrome, nystatin does not reduce systemic or psychological symptoms significantly more than placebo. Consequently, the empirical recommendation of long-term nystatin therapy for such women appears to be unwarranted. PMID- 2247105 TI - Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. AB - BACKGROUND AND METHODS: We describe five patients with underlying neoplasms in whom painful mucosal ulcerations and polymorphous skin lesions developed, usually with progression to blistering eruptions on the trunk and extremities. Histologic examination showed vacuolization of epidermal basal cells, keratinocyte necrosis, and acantholysis. Immunofluorescence testing revealed atypical pemphigus-like autoantibodies in perilesional epithelium and serum from all five patients. We studied the antigenic specificities of the autoantibodies by indirect immunofluorescence and immunoprecipitation, using extracts of 14C-labeled human keratinocytes. IgG purified from the serum of one patient was passively transferred to four neonatal mice to test for pathogenicity. RESULTS: Immunofluorescence testing showed that the autoantibodies bound to the surface of tissues containing desmosomes, including complex and simple epithelia, and myocardium. An identical and unique complex of four polypeptides with molecular weights of 250, 230, 210, and 190 was immunoprecipitated by all serum samples. The 250-kd polypeptide comigrated with desmoplakin I (a protein found in the desmosomes of all epithelia), and the 230-kd antigen comigrated with the antigen of bullous pemphigoid. Cutaneous blisters, a positive Nikolsky's sign, and epidermal and esophageal acantholysis developed in all mice into which the autoantibody was injected. Electron microscopy showed epidermal acantholysis similar to lesions of experimentally induced pemphigus vulgaris. CONCLUSION: These five patients with cancer had a novel acantholytic mucocutaneous disease characterized by autoantibodies that were pathogenic after passive transfer. The autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid and two as yet unidentified epithelial antigens. We suggest the term "paraneoplastic pemphigus" for this disease. PMID- 2247106 TI - The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. AB - BACKGROUND: The enzyme 5-lipoxygenase catalyzes the metabolism of arachidonic acid to form products that have been implicated in the airway obstruction of asthma. We hypothesized that if products of the 5-lipoxygenase pathway are important in mediating this obstruction, then prevention of their formation should decrease the severity of an induced asthmatic response. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, we examined the effect of A-64077, a 5-lipoxygenase inhibitor, on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 patients with asthma. The completeness of 5-lipoxygenase inhibition was confirmed by examining the profile of eicosanoids produced in whole blood ex vivo after activation with the calcium ionophore A-23187. RESULTS: A-64077 decreased the mean (+/- SEM) ionophore induced synthesis of leukotriene B4, a 5-lipoxygenase product, by 74 percent (from 265.3 +/- 30.3 to 69.5 +/- 21.5 ng per milliliter, P less than 0.001), but it did not affect the ionophore-induced synthesis of thromboxane B2, a cyclooxygenase metabolite of arachidonic acid (80.0 +/- 17.1 ng per milliliter before A-64077 vs. 75.8 +/- 14.3 ng per milliliter after A-64077). In concert with the selective inhibition of 5-lipoxygenase by A-64077, the amount of cold, dry air (expressed as respiratory heat exchange) required to reduce the forced expiratory volume in one second by 10 percent was increased by 47 percent after A 64077 (3.0 kJ per minute for placebo vs. 4.4 kJ per minute for A-64077, P less than 0.002). Similar results were obtained when minute ventilation was used as an indicator of outcome (27.5 liters per minute for placebo vs. 39.8 liters per minute for A-64077, P less than 0.005). CONCLUSIONS: Selective inhibition of 5 lipoxygenase by A-64077 is associated with a significant amelioration of the asthmatic response to cold, dry air, suggesting that 5-lipoxygenase products are involved in this response. This approach may be useful in the treatment of asthma. PMID- 2247107 TI - Searching for the yeast connection. PMID- 2247108 TI - Cancers complicating organ transplantation. PMID- 2247109 TI - Leukotrienes in asthma and allergic rhinitis. PMID- 2247111 TI - Abnormal vascular relaxation in essential hypertension. PMID- 2247110 TI - Euthanasia debate. PMID- 2247112 TI - Vitamin A and measles. PMID- 2247113 TI - HIV-associated nephropathy--beneficial effect of zidovudine therapy. PMID- 2247114 TI - A hazard of lay medical treatment for lice. PMID- 2247115 TI - Powder-pole pollicis. PMID- 2247116 TI - Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group. AB - BACKGROUND: Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery. It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment. Patients undergoing noncardiac surgery sometimes have postoperative cardiac events. It would be helpful to know which patients are at highest risk. METHODS: We prospectively studied 474 men with coronary artery disease (243) or at high risk for it (231) who were undergoing elective noncardiac surgery. We gathered historical, clinical, laboratory, and physiologic data during hospitalization and for 6 to 24 months after surgery. Myocardial ischemia was assessed by continuous electrocardiographic monitoring, beginning two days before surgery and continuing for two days after. RESULTS: Eighty-three patients (18 percent) had postoperative cardiac events in the hospital that were classified as ischemic events (cardiac death, myocardial infarction, or unstable angina) (15 patients), congestive heart failure (30), or ventricular tachycardia (38). Postoperative myocardial ischemia occurred in 41 percent of the monitored patients and was associated with a 2.8 fold increase in the odds of all adverse cardiac outcomes (95 percent confidence interval, 1.6 to 4.9; P less than 0.0002) and a 9.2-fold increase in the odds of an ischemic event (95 percent confidence interval, 2.0 to 42.0; P less than 0.004). Multivariate analysis showed no other clinical, historical, or perioperative variable to be independently associated with ischemic events, including cardiac-risk index, a history of previous myocardial infarction or congestive heart failure, or the occurrence of ischemia before or during surgery. CONCLUSIONS: In high-risk patients undergoing noncardiac surgery, early postoperative myocardial ischemia is an important correlate of adverse cardiac outcomes. PMID- 2247117 TI - Congenital absence of the vas deferens. The fertilizing capacity of human epididymal sperm. AB - BACKGROUND: Congenital absence of the vas deferens has been considered a virtually untreatable cause of male sterility. Furthermore, sperm that have not passed through at least the head of the epididymis have been thought to be incapable of causing pregnancy. We attempted to determine whether human sperm that had never passed through the epididymis could fertilize eggs in vitro and whether the technique could be used for men with congenital absence of the vas deferens. METHODS: Twenty-eight men with congenital absence of the vas deferens underwent microsurgical aspiration of sperm from the epididymis and vasa efferentia for attempted in vitro fertilization of their wives' oocytes, with subsequent transfer of embryos. Thirty-two treatment cycles were begun (four were repeat cycles). RESULTS: The most motile sperm were found in the proximal epididymis, at or near the vasa efferentia. Embryos were obtained for transfer in 21 cases (66 percent). Ninety-three embryos resulted from 352 mature oocytes (fertilization rate, 26 percent). Clinical pregnancy was achieved in 10 of the 32 treatment cycles (31 percent). Seven women delivered normal infants, and three miscarried. One of the seven live births was of twins. There were six girls and two boys. When fewer than 10 eggs were retrieved, no pregnancy occurred. When 10 or more eggs were retrieved (20 cases), the pregnancy rate was 50 percent. CONCLUSIONS: Sperm from the proximal caput epididymidis and even sperm from the vasa efferentia (which have never passed through the epididymis) can fertilize the human oocyte in vitro and result in pregnancy with live birth. PMID- 2247119 TI - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. PMID- 2247118 TI - Late pulmonary sequelae of bronchopulmonary dysplasia. AB - BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS: We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS: Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS: Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known. PMID- 2247120 TI - Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. PMID- 2247121 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 52-1990. A 31-year-old HIV-seropositive woman with a cerebral lesion seven years after treatment of carcinoma of the cervix. PMID- 2247122 TI - Bronchopulmonary dysplasia in adulthood. PMID- 2247124 TI - Implications of New York's do-not-resuscitate law. PMID- 2247123 TI - Hospital-acquired infections in children. PMID- 2247125 TI - Warfarin after myocardial infarction. PMID- 2247126 TI - Risk of thrombocytopenia in offspring of mothers with presumed immune thrombocytopenic purpura. PMID- 2247127 TI - Seroprevalence of human immunodeficiency virus infection at sentinel hospitals. PMID- 2247128 TI - Prevention of nosocomial HIV infection in the Soviet Union--an international responsibility. PMID- 2247129 TI - Late renal-artery thrombosis after transplantation associated with intraoperative abdominopelvic compression. PMID- 2247130 TI - Shortness of (fresh) breath--toothpaste-induced bronchospasm. PMID- 2247131 TI - Tinnitus due to low-dose aural aspirin therapy. PMID- 2247133 TI - Neurobiology of drug abuse: learning and memory. A technical review. September 28 29, 1988, Bethesda, MD. Proceedings. PMID- 2247132 TI - The chick as a model system for studying neural processes in learning and memory. PMID- 2247134 TI - Hippocampal theories and the information/computation perspective. PMID- 2247135 TI - Pharmacological and anatomical analysis of fear conditioning. AB - The potentiated startle paradigm measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety, since it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Lesion and electrical stimulation studies on fear-potentiated startle and startle increased by electrical stimulation of the amygdala are being used to define the neural pathways necessary for a visual conditioned stimulus to alter the acoustic startle reflex. The current working hypothesis is that the conditioned stimulus activates the central nucleus of the amygdala through a pathway involving the lateral geniculate nucleus and insular cortex. The central nucleus of the amygdala may then project directly to the acoustic startle pathway, modulating the startle response. More work has to be done to define conclusively the relevant neural pathways involved in fear-potentiated startle. Nonetheless, by combining behavioral, anatomical, physiological, and pharmacological approaches, it will be possible to determine each step along the pathway that mediates the ability of a stimulus signaling fear to alter behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways to affect behavior. Eventually, this approach should help to determine where plastic changes take place along these pathways to mediate the conditioned effects that are being measured and the biochemical processes that are involved. PMID- 2247136 TI - Attentional and motivational effects of psychoactive drugs. PMID- 2247137 TI - Learning as a factor in ethanol tolerance. PMID- 2247138 TI - New approaches to the study of comparative cognition. AB - The rat's memory capacity and performance render it an excellent model of human memory. Rats display serial position, serial anticipation learning, temporal coding, and repetition lag functions as well as utilization of retrospective and prospective codes that are nearly equivalent to that observed for humans. Furthermore, based on the above-mentioned memory performance functions, there are comparable memory-deficit patterns between brain-damaged rats and humans. Thus, the rat can serve as an excellent animal model to evaluate the efficacy of pharmacological treatments or brain damage upon memory. PMID- 2247140 TI - Human gene therapy. First European experiment. PMID- 2247139 TI - Long-term effects of cholinergic agonists on memory. AB - Animal models provide important information about strategies that can be used to assess the effects of chronic exposure to drugs or other compounds. Furthermore, when used in conjunction with analyses designed to utilize the many advantages of animal models to examine learning and memory, these kinds of experiments can have significant ramifications for assessing the mnemonic effects of chronic drug use in people. Finally, given that aging is accompanied by significant deterioration of neurochemical systems, which may compromise the functions of those systems, the results from the experiments with DFP predict that changes in learning and memory abilities that are not apparent in young individuals may begin to surface as those individuals age or may appear following any other kind of insult to their nervous system. PMID- 2247142 TI - Soviet television to raise AIDS funds. PMID- 2247141 TI - Ape import cuts hit research. PMID- 2247143 TI - RU-486. Drug debate expands. PMID- 2247144 TI - Immunology. One hand clapping. PMID- 2247145 TI - Population size bottleneck. PMID- 2247147 TI - Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. AB - Glutamate uptake into nerve and glial cells usually functions to keep the extracellular glutamate concentration low in the central nervous system. But one component of glutamate release from neurons is calcium-independent, suggesting a non-vesicular release that may be due to a reversal of glutamate uptake. The activity of the electrogenic glutamate uptake carrier can be monitored by measuring the membrane current it produces, and uptake is activated by intracellular potassium ions. Here we report that raising the potassium concentration around glial cells evokes an outward current component produced by reversed glutamate uptake. This current is activated by intracellular glutamate and sodium, inhibited by extracellular glutamate and sodium, and increased by membrane depolarization. These results demonstrate a non-vesicular mechanism for the release of glutamate from glial cells and neurons. This mechanism may contribute to the neurotoxic rise in extracellular glutamate concentration during brain anoxia. PMID- 2247146 TI - Crystal structure of an HIV-binding recombinant fragment of human CD4. AB - CD4 glycoprotein on the surface of T cells helps in the immune response and is the receptor for HIV infection. The structure of a soluble fragment of CD4 determined at 2.3 A resolution reveals that the molecule has two intimately associated immunoglobulin-like domains. Residues implicated in HIV recognition by analysis of mutants and antibody binding are salient features in domain D1. Domain D2 is distinguished by a variation on the beta-strand topologies of antibody domains and by an intra-sheet disulphide bridge. PMID- 2247148 TI - A nucleoprotein peptide of influenza A virus stimulates assembly of HLA-B27 class I heavy chains and beta 2-microglobulin translated in vitro. AB - Most cytotoxic T lymphocytes (CTL) recognize epitopes of foreign viral proteins in association with class I major histocompatibility complex (MHC) molecules. Viral proteins synthesized in the cytoplasm require intracellular fragmentation and exposure to the class I antigens for the development of CTL responses. Although indirect evidence for binding of peptides to class I antigens has accumulated, direct binding has only been shown recently. The formation of complexes between peptide and class I antigen may occur in the endoplasmic reticulum (ER) and peptides have been shown to induce assembly of the class I complex. We have translated the messenger RNAs encoding HLA-B27 (subtype 2705) and beta 2-microglobulin in a rabbit reticulocyte lysate supplemented with human microsomal membranes (to mimic ER membranes), in the absence and presence of a peptide derived from the nucleoprotein (residues 384-394) of influenza A virus. This peptide induces CTL activity against target cells expressing the HLA-B27 antigen. Here we report direct evidence that the nucleoprotein peptide promotes assembly of the HLA-B27 heavy chain and beta 2-microglobulin, and that this can occur in the ER immediately after synthesis of the two proteins. PMID- 2247149 TI - Genetic evidence equating SRY and the testis-determining factor. AB - The testis-determining factor gene (TDF) lies on the Y chromosome and is responsible for initiating male sex determination. SRY is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for TDF. Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes or by other deletions. If SRY is TDF, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in SRY. We have tested human XY females and normal XY males for alterations in SRY using the single-strand conformation polymorphism assay and subsequent DNA sequencing. A de novo mutation was found in the SRY gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the SRY gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. PMID- 2247150 TI - Expression of a candidate sex-determining gene during mouse testis differentiation. AB - The development of a eutherian mammal as a male is a consequence of testis formation in the embryo, which is thought to be initiated by a gene on the Y chromosome. In the absence of this gene, ovaries are formed and female characteristics develop. Sex determination therefore hinges on the action of this testis-determining gene, known as Tdy in mice and TDF in humans. In the past, several genes proposed as candidates for Tdy/TDF have subsequently been dismissed on the grounds of inappropriate location or expression. We have recently described a candidate for Tdy, which maps to the minimum sex-determining region of the mouse Y chromosome. To examine further the involvement of this gene, Sry, in testis development, we have studied its expression in detail. Fetal expression of Sry is limited to the period in which testes begin to form. This expression is confined to gonadal tissue and does not require the presence of germ cells. Our observations strongly support a primary role for Sry in mouse sex determination. PMID- 2247151 TI - A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. AB - The primary decision about male or female sexual development of the human embryo depends on the presence of the Y chromosome, more specifically on a gene on the Y chromosome encoding a testis-determining factor, TDF. The human sex-determining region has been delimited to a 35-kilobase interval near the Y pseudoautosomal boundary. In this region there is a candidate gene for TDF, termed SRY, which is conserved and specific to the Y chromosome in all mammals tested. The corresponding gene from the mouse Y chromosome is deleted in a line of XY female mutant mice, and is expressed at the expected stage during male gonadal development. We have now identified a mutation in SRY in one out of 12 sex inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome. The four-nucleotide deletion occurs in a sequence of SRY encoding a conserved DNA-binding motif and results in a frame shift presumably leading to a non-functional protein. The mutation occurred de novo, because the father of the sporadic XY female that bears it has the normal sequence at the corresponding position. These results provide strong evidence for SRY being TDF. PMID- 2247152 TI - Fitness of RNA virus decreased by Muller's ratchet. AB - Why sex exists remains an unsolved problem in biology. If mutations are on the average deleterious, a high mutation rate can account for the evolution of sex. One form of this mutational hypothesis is Muller's ratchet. If the mutation rate is high, mutation-free individuals become rare and they can be lost by genetic drift in small populations. In asexual populations, as Muller noted, the loss is irreversible and the load of deleterious mutations increases in a ratchet-like manner with the successive loss of the least-mutated individuals. Sex can be advantageous because it increases the fitness of sexual populations by re creating mutation-free individuals from mutated individuals and stops (or slows) Muller's ratchet. Although Muller's ratchet is an appealing hypothesis, it has been investigated and documented experimentally in only one group of organisms- ciliated protozoa. I initiated a study to examine the role of Muller's ratchet on the evolution of sex in RNA viruses and report here a significant decrease in fitness due to Muller's ratchet in 20 lineages of the RNA bacteriophage phi 6. These results show that deleterious mutations are generated at a sufficiently high rate to advance Muller's ratchet in an RNA virus and that beneficial, backward and compensatory mutations cannot stop the ratchet in the observed range of fitness decrease. PMID- 2247153 TI - Solution structure of the DNA-binding domain of the oestrogen receptor. AB - Steroid hormone receptors control gene expression through binding, as dimers, to short palindromic response elements located upstream of the genes they regulate. An independent domain of approximately 70 amino acids directs this sequence specific DNA binding and is highly conserved between different receptor proteins and related transcription factors. This domain contains two zinc-binding Cys2 Cys2 sequence motifs, which loosely resemble the 'zinc-finger' motifs of TFIIIA. Here we describe the structure of the DNA-binding domain from the oestrogen receptor, as determined by two-dimensional 1H NMR techniques. The two 'zinc finger'-like motifs fold to form a single structural domain and are thus distinct from the independently folded units of the TFIIIA-type zinc fingers. The structure consists of two helices perpendicular to each other. A zinc ion, coordinated by four conserved cysteines, holds the base of a loop at the N terminus of each helix. This novel structural domain seems to be a general structure for protein-DNA recognition. PMID- 2247154 TI - Set-asides in health? PMID- 2247155 TI - Biologists lash back. PMID- 2247156 TI - NIH propose cost benefit rules in grant reforms. PMID- 2247157 TI - Monkey case in Supreme Court. PMID- 2247158 TI - Catalytic antibodies. On to the second generation. PMID- 2247159 TI - Cell biology. Many routes lead to the pole. PMID- 2247160 TI - Equal animals. PMID- 2247161 TI - Forlorn hope for malaria vaccine? PMID- 2247162 TI - Evidence for multinuclear metal-ion complexes at solid/water interfaces from X ray absorption spectroscopy. AB - Metals dissolved in natural waters often become sorbed onto oxide or clay minerals, so that prediction of their chemical behaviour and transport properties requires knowledge of the structure and bonding of metal species at the solid/water interface. For many sorption systems, X-ray absorption spectroscopy (XAS) can be used to determine the identity and number of nearest-neighbour atoms and interatomic distances in aqueous complexes on solid surfaces, and thus to identify the dominant type of surface complex and the partitioning mechanism. Here we describe an XAS study of divalent cobalt (Co(II)) complexes sorbed on three different solids, gamma-Al2O3, rutile (TiO2) and kaolinite (Al2Si2O5(OH)4). We find direct evidence for the presence of multinuclear sorption complexes at surface coverages below one monolayer of Co(II) atoms. Our spectroscopic data reveal distinct differences in the number of coordinating atoms and interatomic distances in the surface complexes formed on each of the solids at the same sorption density. These results suggest that different oxide and clay surfaces influence the structure and properties of aqueous surface complexes, and therefore must be accounted for in models of metal-ion sorption. PMID- 2247163 TI - Laser inactivation of fasciclin I disrupts axon adhesion of grasshopper pioneer neurons. AB - A molecular mechanism for selective axonal adhesion is a central question of neural development. Cell adhesion molecules have been identified, but it has been difficult to ascribe functions for these proteins in vivo. Here we show that the neuronal membrane glycoprotein fasciclin I has a role in the adhesion of sister axons during the development of the grasshopper limb bud. To do this we used a new technique, chromophore-assisted laser inactivation (CALI), which causes the precisely timed thermal denaturation of specific proteins by laser light targeted through a dye-labelled antibody, without any other observable damage to living cells. This can be achieved by relaxation of the laser-excited dye which releases heat to denature the bound protein; the rapid dissipation of heat with distance insulates unbound proteins from damage. CALI is a molecular analogue of cellular laser ablation and provides an unprecedented level of spatial and temporal resolution. Using dye-labelled antibodies that recognize fasciclin I, CALI disrupts fasciculation of the pioneer neurons without affecting their growth or guidance. PMID- 2247164 TI - Phage antibodies: filamentous phage displaying antibody variable domains. AB - New ways of making antibodies have recently been demonstrated using gene technology. Immunoglobulin variable (V) genes are amplified from hybridomas or B cells using the polymerase chain reaction, and cloned into expression vectors. Soluble antibody fragments secreted from bacteria are then screened for binding activities. Screening of V genes would, however, be revolutionized if they could be expressed on the surface of bacteriophage. Phage carrying V genes that encode binding activities could then be selected directly with antigen. Here we show that complete antibody V domains can be displayed on the surface of fd bacteriophage, that the phage bind specifically to antigen and that rare phage (one in a million) can be isolated after affinity chromatography. PMID- 2247165 TI - Today's SCID-hu mouse. PMID- 2247166 TI - [A positive approach to the obstructive sleep apnea syndrome]. PMID- 2247167 TI - [EEC recommendations concerning drug trials in humans]. PMID- 2247168 TI - [Transvaginal echography: a new acquisition]. PMID- 2247169 TI - [Splenic cysts. Decapsulation treatment or partial splenectomy]. PMID- 2247170 TI - [Effective treatment of essential trigeminal neuralgia using percutaneous selective heat coagulation of Gasser's ganglion]. AB - Trigeminal neuralgia may be treated in several ways. In the present study the efficacy of a selective percutaneous radiofrequency neurolysis in the gasserian ganglion was evaluated in 172 patients. A complete result was seen in 96.5% of the patients. The recurrence rate within 2 years amounted to 28.3%. Forty-seven patients underwent several treatments with a maximum of four within this period of time. The recurrence rate in the entire study population after 2 years was 8.1%. The mean follow-up period was 50 months (range 9-90 months). Except for the occurrence of corneal anaesthesia in 4% of the patients no serious complications were encountered. PMID- 2247171 TI - [The clinical symptoms in post-traumatic dystrophy]. AB - The clinical signs and symptoms in 441 patients with post-traumatic dystrophy were recorded. This form of dystrophy occurred three times as often in females as in males and twice as often in the arms as in the legs. In 5% of the patients the first symptom is a cold extremity; these patients run a greater risk of major sequelae. Exacerbation of the symptoms under influence of muscular exercise proved to be an important prognostic factor. A large proportion of the referred patients proved to have undergone a treatment aimed at elimination of the sympathetic nervous system, without success. Post-traumatic dystrophy can impede all structures and functions of the affected extremity and may result in major sequelae and disablement. The pseudoparalysis of the later phase may be mistaken for conversion. PMID- 2247172 TI - [The effects of the cholesterol synthesis inhibitor simvastatin in patients with hypercholesterolemia with and without diabetes mellitus]. AB - We studied the short-term effects of simvastatin on lipid variables in 33 dyslipidemic patients without and 18 with diabetes mellitus who were on a lipid lowering diet for at least 3 months. Six diabetic patients had type I, and 12 had type II diabetes mellitus, of whom 5 were using insulin. In the whole group total cholesterol decreased by 28%, from 9.35 (SD 2.10) mmol/l to 6.69 (SD 1.47) mmol/l after 3 months and 6.60 (SD 1.27) mmol/l after 6 months (mean daily dose of simvastatin 21 (SD 12) mg). Calculated LDL-cholesterol showed a decrease of 38%, HDL-cholesterol increased by 10% and plasma triglycerides decreased by 13%. In patients receiving 10, 20, or 40 mg simvastatin daily, the following changes were observed: total cholesterol -26, -31 and -34% and LDL-cholesterol -37, -38 and 39%, respectively. The effect of simvastatin in the diabetic patients was comparable with that in the non-diabetic individuals, although in the diabetics LDL-cholesterol before therapy was lower, as was the daily dose of simvastatin after 6 months (14 versus 24 mg). In the diabetic patients blood glucose control, measured as HbA1c, was not affected. One patient discontinued therapy because of stomach complaints. Our results show that a low daily dose (10 mg) of simvastatin effectively lowers plasma total and LDL-cholesterol and that the drug can be safely used in diabetic patients. PMID- 2247173 TI - [A patient with toxic shock syndrome following correction of the nasal septum]. AB - A male aged 30 suffered from toxic shock syndrome after septorhinoplasty with positioning of a tampon. Initial treatment consisted of removing the tampon and supportive care, as a result of which the patient recovered. The patient was a carrier of Staphylococcus aureus which produced toxic shock syndrome toxin-I (TSST-I). Anti-TSST-I antibodies were already found in the serum in the initial phase of the disease. PMID- 2247174 TI - [AIDS 1982-1989]. PMID- 2247175 TI - [AIDS and adoption]. PMID- 2247176 TI - [Good clinical practice; the revised recommendations for Europe]. PMID- 2247177 TI - [Controversies concerning thrombolysis in myocardial infarct; impressions from various symposium discussions]. PMID- 2247178 TI - [Biliary ascariasis as complication following cholecystectomy for cholelithiasis]. PMID- 2247179 TI - [Current status and perspectives of autopsy]. PMID- 2247180 TI - [Measurement of involuntary urine loss in women]. PMID- 2247181 TI - [Clinical procedures in patients with chronic coma; a contribution from nursing home medicine]. PMID- 2247182 TI - [Breast carcinoma following primary augmentation surgery of the breast]. PMID- 2247183 TI - [Current perspectives in the pathogenesis and the treatment of duodenal ulcer]. PMID- 2247184 TI - [Initial results of anonymous HIV screening in the United States]. PMID- 2247185 TI - [Urinary incontinence in the elderly; worth an examination?]. PMID- 2247186 TI - [Percutaneous antegrade treatment of calculi located in the upper ureter using a flexible uretero-renoscope]. AB - In selected cases of upper ureteric stones, especially in the impacted ureteric stone, when first line treatment with ESWL has failed, an antegrade flexible uretero-renoscopic treatment may offer a good alternative. Treatment results are presented in 9 patients with 10 upper ureteric stones. During 10 procedures the antegrade flexible uretero-renoscopic technique proved to be a reliable method when using grasping methods, electrohydraulic disintegration or a combination of both techniques, with no failures encountered. IVU at 3 months was unremarkable in all patients. PMID- 2247187 TI - [localized fibrous tumors of the pleura]. AB - The localized fibrous tumour of the pleura, also named localized fibrous mesothelioma or fibroma of the pleura, is a very rare tumour with a benign behaviour. Its origin, clinical behaviour and prognosis are very different from malign mesothelioma. In a 33-year period 22 patients with this diagnosis were surgically treated. The prognosis was excellent. In this article the clinical and radiological signs, as well as the diagnosis and therapy are discussed. PMID- 2247188 TI - [Multiple births in The Netherlands, 1900-1988]. AB - There are an estimated 120,000 twins and other multiples (all still alive) in The Netherlands. The age of this population (i.e. a quarter of a million persons, 1.6% of the total population) is slightly lower compared with The Netherlands as a whole. Alterations in the structure of mother's age and birth order can only partly explain the observed changes in multiple birth frequencies. The recent increase may be due to medical treatment of women with fertility problems. In addition dizygotic twin births appear to be largely responsible for the total development in multiple births. The changes in birth patterns which relate to the demographic variables age of mother and birth order, are hardly responsible for the decline of stillbirths, perinatal and infant mortality among twins and other multiples. This improvement can be ascribed mainly to progress in medical care. In spite of this improvement, the differences compared with singles are still considerable: the stillbirth rate for twins and other multiples is 2.5 times that for singles; the perinatal mortality rate and the infant mortality rate are about four times as high. However, in the first few years of life of twins and other multiples the age-specific mortality risk declines at such a rate that as early as the third year after birth there is hardly any difference with respect to the singles. PMID- 2247189 TI - [Utility assessment in clinical decision making]. AB - In clinical decision analysis a quantitative value is attached to a longevity or a life quality by means of utility assessment. The actual value of the utility can determine the result of the decision analysis. In this article utility theory is briefly discussed. Four kinds of utility tests (direct scaling methods, the basic reference gamble, the time trade-off test and additive conjoint measurement) are introduced on the basis of an example and their pros and cons are discussed. It is concluded that additive conjoint measurement has the best formal infrastructure, but that the test method is not always easily applicable. PMID- 2247190 TI - [2 successful treatments with extracorporeal membrane oxygenation in neonates with severe respiratory problems]. AB - We report the successful treatment with extracorporeal membrane oxygenation of two Dutch neonates with severe respiratory insufficiency, due to meconium aspiration syndrome and persistent fetal circulation respectively. During this procedure part of the cardiac output is led outside the body via a venous cannula in the right atrium, oxygenated in a membrane oxygenator, rewarmed to the patient's body temperature in a heat exchanger and returned to the patient via a cannula in the carotid artery debouching into the aortic arch. PMID- 2247191 TI - [Cholesterol determination and age]. PMID- 2247192 TI - [Induction of cytotoxicity from human lymphocytes coated with bispecific antibody against human glioma cells]. AB - A bifunctional hetero-F (ab') 2 fragment containing the Fab portions from anti CD3 and anti-glioma monoclonal antibodies was prepared. The antibody simultaneously recognized two different molecules, the CD3 complex on effector T cells and human glioma-associated antigens on target glioma cells. This bispecific F (ab') 2 fragment induced peripheral blood lymphocytes (PBLs) from healthy donors to lyse cells of the human glioma cell line, U251MG, that is resistant to natural killer cell-mediated cytolysis. Compared with lymphokine activated killer (LAK) activity which is obtained by exposure to interleukin (IL) 2 for more than 3 days, the maximum bispecific antibody-dependent cytotoxicity can be generated only after 24 hour exposure to IL-2. And cytotoxicity of lymphocytes triggered by the bispecific antibody was dependent upon the concentration of IL-2 in the culture medium. The effect of the bispecific antibody on LAK cells was tested in patients suffering from malignant glioma. One patient who received specific targeting therapy (LAK plus bispecific antibody) showed the disappearance of high density tumor mass from CT scan. But the patient who received only LAK therapy showed the recurrence of tumor one year after LAK treatment. These are preliminary data, but may be a promising approach in cancer immunotherapy. PMID- 2247193 TI - [Interstitial hyperthermia of malignant gliomas with implant heating system]. AB - Twenty four cases of malignant gliomas, histologically 12 glioblastomas, 10 astrocytoma GIII and 2 astrocytoma GII, were treated by interstitial hyperthermia with Implant Heating System (IHS). IHS has three major parts, generator of high frequency (240KHz), magnetic coil and metal implant manufactured from FePt alloy. Theoretically the brain tumor can be heated by heat conduction through the heated implants. Several implants were placed inside the brain tumor directly by operation, or by CT stereotactic procedure. The patients were divided into two groups according to the tumor location as (A) in cortical or subcortical region (13 cases) and (B) in thalamus or basal ganglia (11 cases). Hyperthermia, 60 minutes each, 2 to 3 times per week, was safely repeated in all the cases. External irradiation was always combined with hyperthermia in most of the cases and with chemotherapy in some of them. Follow-up CTs demonstrate a remarkable response in many cases of B group. In fact ICR, 4PR and 3MR were achieved in this group, resulting in 45.5% of the response. In contrast gliomas in A group showed a less favorable response, resulting in 23.1% of the response (3 PRs in 13 cases). Although the overall response rate was not so high, it seems to be encouraging that gliomas in thalamus and basal ganglia, those which are usually unresectable, showed a good response. More favorable results can be expected by further improvement of the system and related techniques. PMID- 2247194 TI - [Experimental analysis of anti-tumor cytotoxic mechanism for hybrid resistance to mouse neuroblastoma]. AB - A spontaneous neuroblastoma (NB-85, H-2a/a) was tested for hybrid resistance (HyR) after subcutaneous (s.c.) inoculation into syngeneic and semisyngeneic mice. The hybrids (F1) (H-2a/b) between A/Sn and Leaden mice and the F1 between A/Sn X C57BL/6 mice were more resistant to the s.c. inocula of 10(6) to 5 X 10(5) cells than syngeneic recipients. Thymectomy, followed by irradiation and fetal liver reconstitution, abrogated the HyR against NB-85, whereas intravenous (i.v.) administration of anti-asialo-GM1 antibodies had no influence on the resistance. Surface phenotypic analysis revealed that NB-85 expressed H-2 Kk (-), Dd (+) and beta 2-microglobulin (-), showing a dissociation of the cell surface. Anti-H-2a specific cytotoxic T lymphocytes exhibited a significant lytic activity against NB-85, while NB-85 was highly refractory to natural killer cell (NK)-mediated lysis. In vivo NK-mediated rejection assays showed that 125I-iododeoxyuridine (IUdR) labeled NB-85 cells were not eliminated more efficiently from the highly resistant F1 hybrids than from the parental strain. Furthermore, genotypic study with segregating (A/Sn X Leaden) F1 X A/Sn backcross mice showed that the HyR was attributable primarily to heterozygosity within the H-2 complex. Taken together, it was suggested that the HyR to an NK-resistant mouse NB-85 neuroblastoma might involve a T cell-dependent immunosurveillance with H-2 genetic control. PMID- 2247195 TI - [Intraoperative ABR monitoring during cerebello-pontine angle surgery]. AB - Intraoperative auditory brainstem response (ABR) monitoring was performed in 27 patients undergoing C-P angle surgery (12: hemifacial spasm, 10: trigeminal neuralgia, 2: glossopharyngeal neuralgia, 3: C-P angle tumor, 2 epidermoid, 1 meningioma). Because of the introduction of this method, no patient suffered from postoperative hearing disturbance in this series. During C-P angle surgery, the wave V of ABR changes according to the retraction of the cerebellum and the manipulation of the eighth cranial nerve. Many authors have discussed this change, however the timing and the mechanism of disappearance of wave V is unclear. Accordingly, the authors discussed the correlation between the prolongation of wave V latency and its amplitude. The wave V amplitude was measured from the positive peak of wave V to the next negative peak. Then, the correlation between the prolongation of wave V latency and its reduction ratio (%) of amplitude was represented as a parabola. The wave V reduces its amplitude when the prolongation of the latency is from 1.5 ms to 2.0 ms. Once the prolongation of the latency is over 1.5 ms, the amplitude of wave V seems to be reduced suddenly, because it takes over 1'30'' to finish each record. But the authors demonstrated the gradual reduction of the amplitude of wave V in Figure 3. As mentioned above, the prolongation of wave V latency must be less than 1.5 ms, and the neurosurgeon must recognize this turning point during C-P angle surgery. PMID- 2247196 TI - [Facial nerve preservation in the region of the zygomatic arch]. AB - In order to preserve the frontotemporal branch of the facial nerve in frontotemporal and trans-zygomatic craniotomies, electromyographic responses from the facial muscles were recorded preoperatively. Incising the frontotemporal branch of the facial nerve could be avoided by identifying the crossing point of the frontotemporal branch of the facial nerve on the superior border of the zygomatic arch. The crossing points were investigated in 20 patients and in most cases they existed between 2 cm and 6 cm from the anterior border of the external auditory canal. Another important point to preserve the facial nerve is to conserve the layer in which the facial nerve is included. Therefore, the surgical anatomy in the region of the zygomatic arch and temporal area was reviewed in detail. This knowledge is crucial for neurosurgeons to dissect precisely in this region without causing postoperative facial palsy. PMID- 2247197 TI - [Diffuse stenotic changes in the large intracranial arteries following irradiation therapy for medulloblastoma; case report]. AB - We reported a case of a patient who developed a diffuse stenotic change in the large intracranial arteries and repeated episodes of cerebral infarction after irradiation therapy for medulloblastoma. A three-year-old girl underwent the subtotal removal of cerebellar medulloblastoma and the subsequent irradiation therapy in the whole brain and spine (30 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). Two years later, she again underwent surgery and irradiation therapy because a recurrence of medulloblastoma had manifested itself in the frontal lobe; (40 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). One and half years after the second irradiation, she started suffering from frequent and refractory cerebral ischemic attacks. Cerebral angiography revealed a diffuse narrowing, and multifocal stenoses in the bilateral anterior and middle cerebral arteries. Computerized tomography demonstrated multiple cerebral infarctions. Her neurological condition deteriorated because of recurring strokes and she died at ten years of age. Most of the reported cases of patients who developed stenotic arteriopathy were children in the first decade of their life, and who were irradiated for parasellar brain tumor of low malignancy. Stenotic arteriopathy after irradiation has rarely been recognized in patients with malignant brain tumor. However, life expectancy is increasing even for those with malignant brain tumor, and it may make stenotic arteriopathy after irradiation recognized more commonly in patients with malignant brain tumor. Careful irradiation and subsequent angiographical examination should be required even in patients with malignant brain tumor. PMID- 2247198 TI - [C-P angle epidermoid carcinoma: a case report]. AB - The patient, a 39-year-old man, underwent initial surgery for total removal of a left C-P angle tumor histologically diagnosed as epidermoid carcinoma. Postoperative irradiation therapy was administered over the whole brain and spinal cord, 50 Gy and 20 Gy respectively. The patient was then released without symptoms. 15 months later, he was readmitted for paraparesis and urinary retention. CT scan revealed no tumor recurrence in the intracranial area but did show intraspinal cyst of the lower thoracic level. After cyst-subarachnoid shunt, severe acute hydrocephalus was shown on CT scan. His general condition progressively deteriorated. Ten days after the shunt operation, he died of systemic bleeding tendency and cachexia. During surgery, the authors obtained dark yellowish fluid from the intraspinal cyst. Gene survey of the specimen from the cyst wall disclosed abnormality. It is important in the diagnosis of primary intracranial epidermoid carcinoma that we rule out the existence of extracranial cancer and direct invasion through the dura. Though epidermoid carcinoma can be fatal, radiotherapy was an efficacious treatment in the present case, as well as in three other reported cases. PMID- 2247199 TI - [Anastomosis of the superficial temporal artery to the middle cerebral artery for occlusive disease of the bilateral internal carotid arteries with dementia]. AB - Two cases are reported of occlusive disease of the bilateral internal carotid arteries with dementia in which the anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA bypass) resulted in marked improvement in clinical aspects. One patient was a 29-year-old male who complained of transient weakness of the extremities and memory impairment. Computerized tomography (CT) scans showed multiple small infarctions, while cerebral angiography demonstrated findings of Moya-like disease. The cognitive function tests were subnormal and the study of cerebral blood flow (CBF study) showed diffuse low flow in both hemispheres. Based on his clinical symptoms and CBF study, the STA-MCA bypass was performed on both sides in two stages without complications. Postoperatively, his clinical symptoms and cognitive function improved gradually, in accordance with increased CBF in both hemispheres. Six months after the operation, cognitive function tests were within normal limits. Another patient was a 61-year-old hypertensive male who complained of motor weakness, impairment of memory and urinary incontinence. CT scans showed multiple small infarctions, while cerebral angiography revealed occlusion of both internal carotid arteries at the cervical portion. The cognitive function was at the pre dementia level, and CBF study revealed diffuse low flow in both hemispheres. Based on the clinical symptoms and CBF study, the STA-MCA bypass was performed on both sides in two stages. Postoperatively, clinical symptoms and cognitive function markedly improved. From our results, the diagnosis of vascular dementia, and indications for the use of STA-MCA bypass in this category of patients are discussed. PMID- 2247200 TI - [A case of ganglioglioma with choked disc]. AB - A case of ganglioglioma associated with choked disc is reported. A 19-year-old girl was admitted to our hospital because of blurred vision. Neurologically, the patient had nothing but choked disc. The CT showed a large cystic mass with calcification in the left parieto-occipital lobe. The MRI revealed that the cyst was delineated by a membrane and that its dorsal side was solid, showing enhancement by Gd-DTPA. Cerebral angiography showed no tumor stain. Left parieto temporo-occipital craniotomy was performed and the tumor was removed subtotally. Histopathological examination demonstrated the typical pattern of ganglioglioma. The most common symptom of ganglioglioma is convulsions. Symptoms of increased intracranial pressure have been reported sporadically in the literature. It was clinically noted that the cause of the increased intracranial pressure in this patient was enlargement of the cyst associated with ganglioglioma. PMID- 2247201 TI - [Cerebellopontine angle lipoma: a case report]. AB - A surgical case of lipoma in the cerebellopontine angle in a 37-year-old man is reported. Cerebellopontine angle lipomas are very rare lesions that differ from other intracranial lipomas in that they typically present slowly progressive focal symptoms identical to those in other tumors of this location. The patient's chief complaints were left hearing disturbance and dizzy spells. Computed tomography showed a very low density lesion (-99.3 Hounsfield units) with no enhancement in the left cerebellopontine angle. Magnetic resonance imaging (0.15T) was subsequently performed. The relative T1 weighted image showed a lesion of high signal intensity in the left cerebellopontine angle. The tumor was adherent to both the brainstem and the cranial nerves involved. On dissection, it was quite hemorrhagic. The tumor could only be partially resected because of the embedded cranial nerves and vascularity. The authors review the literature on this rare tumor and discuss the clinical appearance. Radiological assessment including CT and MRI and management of this lesion were also discussed. PMID- 2247202 TI - [A case of transsphenoidal meningoencephalocele]. AB - A 6-year-old boy was sent to us due to basal meningoencephalocele detected by MRI. He had had a past history of strabismus and morning glory syndrome since 6 months of age, as well as hypopituitary dwarfism since he was 3 years old. On admission, physical examination revealed hypertelorism and left coloboma. Laryngoscopic examination revealed a round mass covered by normal nasal mucose in the midline of the tegmen of the choana. X-ray tomogram and CT scan demonstrated an isodense mass protruding into the nasopharyngeal cavity through a bony defect of the sella turcica. Right carotid angiogram showed stenosis of the right internal carotid artery and abnormal fine vessels in the basal ganglia similar to basal Moyamoya network. There was an irregular filling of the right anterior cerebral artery. Left carotid angiogram showed an irregular filling of the left middle cerebral artery. MRI showed an anterior part of the third ventricle descending into, and the meningocele protruding into the nasopharyngeal cavity. It also showed a stalk extending from the hypothalamus into the meningocele, but the pituitary gland was not recognized. The meningocele was of the same signal intensity as CSF in both T1 and T2 weighted images. Growth hormone deficiency was confirmed by radioimmunoassay of the peripheral blood. An operation was scheduled transcranial to prevent snoring during sleep at age 9. The stalk was observed behind the chiasm during the operation, but a radical operation was not performed because of a possibility of postoperative hypothalamic-pituitary dysfunction. Transsphenoidal encephalocele is rare. So far as we could see, only 30 cases have been reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247203 TI - [Three cases of carotid anterior cerebral anastomosis]. AB - Three cases are presented with rare carotid-anterior cerebral anastomosis (anomalous ACA) originating from the internal carotid artery at the level of the origin of the ophthalmic artery, running first underneath and then between both optic nerves, and finally joining the anterior communicating artery. Case 1 (47 year-old woman) and case 2 (56 year-old man) were both admitted with subarachnoid hemorrhage from a ruptured aneurysm, which was located at the anomalous ACA (carotid-ACA anastomosis). Case (61 year-old man) was diagnosed as having left occipital intracerebral hematoma on CT, and bilateral anomalous ACA was found on angiograms. This anomalous ACA is very rare; only 21 cases have been reported in the literature. Several synonyms have been proposed as follows: 1) interoptic course of the anterior cerebral artery (ACA), 2) interoptic course of ACA, 3) an anomalous branch of the internal carotid artery (ICA) and 4) an anastomosis between the ICA and the ACA (carotid-ACA anastomosis). In cases with this carotid ACA anastomosis, coexisting intracranial aneurysm has been reported. However, this is the first report of ruptured aneurysm located at the anomalous ACA itself. Case 1 and 2 were operated on through the ipsilateral pterional approach and the aneurysm was successfully clipped. Postoperative course was uneventful in each case. Case 3 was treated conservatively. From the angiographical and operative findings, we prefer to use "carotid-anterior cerebral artery anastomosis" as the medical terminology best suited to describe this condition. PMID- 2247204 TI - [Encephalo-duro-arterio-synangiosis: surgical anatomy associated with procedure]. PMID- 2247205 TI - Specialization of the right hemisphere for visuomotor control. AB - The accuracy of saccades directed towards the remembered positions of targets in left (LVF) or right (RVF) visual hemifield was measured. The majority of right handed subjects were found to be more accurate at directing their gaze to locations in the LVF than in the RVF, suggesting that the right hemisphere is superior to the left in oculomotor control. Even after completion of a corrective saccade following the primary saccade, subjects systematically undershot target direction and overshot target depth, suggesting that visual feedback normally plays an important role in the fine guidance of gaze after the completion of a primary saccade. PMID- 2247206 TI - Facial asymmetries in the spontaneous response to positive and negative emotional arousal. AB - Facial asymmetries during emotional arousal were studied under conditions designed to produce spontaneous responses. Subjects who performed a difficult verbal task reported unpleasant emotions, tested high on state anxiety and showed greater changes in left than right-sided composite photographs compared to the relaxed state. Subjects who performed an easy version of the same task reported positive emotions, tested significantly lower on state anxiety and showed greater changes in right sided composites. The pattern of results is consistent with the lateralization of function for positive and negative emotions and not for cognitive task variables, however, a cognitive basis for these results cannot be categorically excluded. The role of arousal in the appearance of facial asymmetries is discussed. PMID- 2247207 TI - Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients. AB - Patients with frontal lobe lesions, amnesic patients with Korsakoff's syndrome, other (non-Korsakoff) amnesic patients, and control subjects were given tests of memory for temporal order. In the first experiment, subjects were presented with a list of 15 words and then asked to reproduce the list order from a random array of the words. In the second experiment, they were asked to arrange in chronological order a random display of 15 factual events that occurred between 1941 and 1985. In both experiments, patients with frontal lobe lesions were impaired in placing the items in the correct temporal order, despite normal item memory (i.e. normal recall and recognition memory for the words and facts). The two groups of amnesic patients exhibited impaired memory for temporal order as well as impaired item memory. Patients with Korsakoff's syndrome exhibited poorer temporal order memory than the other amnesic patients, despite similar levels of item memory. These findings demonstrate that patients with frontal lobe lesions have difficulty organizing information temporally. Patients with Korsakoff's syndrome, who have both diencephalic and frontal damage, have memory impairment together with a disproportionate deficit in memory for temporal order. PMID- 2247209 TI - Cerebral language lateralization: evidence from intracarotid amobarbital testing. AB - Cerebral language lateralization was investigated in 103 patients undergoing intracarotid amobarbital testing as part of their diagnostic work-up for epilepsy surgery. Inclusion criteria included adequate bilateral intracarotid amobarbital studies and no radiologic lesion in areas other than the temporal lobe. Language was evaluated with respect to strict presence or absence of language representation, in which a patient was considered to have bilateral language despite potentially having asymmetric language representation, and with respect to forced relative hemispheric dominance, in which a single side could be considered dominant despite bilateral language representation. Seventy-nine patients displayed exclusive left hemisphere language representation, two patients showed exclusive right hemisphere language representation, and 22 patients had language represented in each hemisphere. In the 22 patients with bilateral language, an asymmetry was present in 17 cases (13 L greater than R, 4 R greater than L). These data indicate that language restricted only to the right hemisphere is rare, and that in the absence of purely left hemisphere language, most patients exhibit bilateral representation. Previously reported incidence of exclusive right hemisphere language may be an artifact of dichotomizing a continuous variable. PMID- 2247208 TI - The effects of lateralized temporal lobe dysfunction on formal and semantic word fluency. AB - Word fluency performance was studied in 32 patients with unilateral temporal lobe epilepsy (TLE) and 25 healthy dextral controls. Two word fluency tasks were administered conforming to either formal-based criteria or semantic-based criteria. Performance for TLE patients was assessed both pre-operatively and approximately 1 week following anterior temporal lobectomy. Both formal and semantic word fluency decreased regardless of resection laterality. Left TLE patients performed significantly worse at both pre- and post-operative assessments compared to the right TLE patients, while right TLE patients performed significantly poorer than controls on all verbal fluency criteria at pre- and post-operative assessments. In addition, both TLE and control groups produced significantly fewer formal and semantic words during the second 30-sec portion of each task. These findings are discussed in terms of temporal lobe contributions to word fluency production and lexical semantic processing. PMID- 2247210 TI - Parkinson's disease patient's behaviour in a covered maze learning task. AB - A computerized maze task was constructed that allowed only partial vision of the maze structure and produced measurements for separate analysis of cognitive processes described as impaired in Parkinson's disease. Eighteen patients suffering from mild Parkinson's disease and 18 individually matched normal controls were investigated. Baseline task response times were found to be identical for both groups. Differences between patients' and controls' performance could be related to (a) a response bias in Parkinson patients that favoured repetition of the previous action and slowed down shifting and (b) an impairment of multistep plan generation. It is speculated that the response bias reflects the disinhibition of cortico-thalamo-cortical reverberation loops which results from striatal dopamine depletion. PMID- 2247211 TI - Cross-modal functions in alcoholism and aging. AB - Two experiments were performed to measure separate aspects of cross-modal functions in normal and alcoholic research participants: matching, and utilization of concepts. In Experiment 1, cross-modal equivalence-matching was measured, i.e. the ability to select in a second modality (e.g. vision), the same stimulus that was first presented in a different modality (e.g. touch). Experiment 2 measured cross-modal transfer of information about stimulus dimensions, i.e. the ability to recognize and use the concepts of texture and form, based upon prior experience solving tactual problems, to solve visual problems. Fifty-five normal and alcoholic research participants comprised the following five groups: 13 young normals (YN) and 10 young alcoholics (YA), 28-48 years of age; 13 older normals (ON) and 14 older alcoholics (OA), 50-71 years of age; and 5 alcoholic Korsakoff patients (K), 55-68 years of age. Separate subgroups of 9 age-matched ONs and 9 OAs were devised for purposes of statistical analyses of data involving the 5 Ks. Results of the experiments indicated that aging is associated with decline in tactual discrimination ability. Further, cross-modal functions appear to be compromised by alcoholic Korsakoff's disease, and--to a lesser extent--by the combined effects of alcoholism and normal chronological aging. Brain mechanisms important for normal cross-modal functions are discussed. PMID- 2247212 TI - Opposite musical-manual interference in young vs expert musicians. AB - Cerebral lateralization for music has been studied through a music-manual interference paradigm (tapping) in a group of young musicians (seven males and seven females) attending the 1st and 3rd intermediate grades of Udine's "J. Tomadini" State Conservatory of Music and in a group of graduated expert musicians or higher course students during the execution of three distinct tasks (singing notes, whistling a melody and singing a melody). A significant superiority of the right hemisphere (greater degree of interference with the left hand) in these tasks has been found in young musicians, while an opposite left hemisphere superiority (greater degree of interference with the right hand) was evident in the expert musicians. Other differences between sexes and tasks were not significant. The modification of hemispheric specialization occurring during academical musical training are discussed in terms of the role of education in the cerebral organization of superior cognitive functions. PMID- 2247213 TI - Spectral analysis of the EEG (alpha rhythm) and activity in the left hemisphere: the effects of lateral gaze. AB - This study tests the effect of maintaining right and left lateral gaze during a writing task which preferentially implicates the left hemisphere using an asymmetry parameter calculated from the spectral power of the alpha rhythm (RP LP/RP + LP) in a right-handed patient undergoing the same experimental regimen nine times. A six derivation EEG was recorded. Maintaining left lateral gaze (toward the active hemisphere) removes the lateralization found during writing while staring straight ahead whereas maintaining right lateral gaze (toward the side opposite the active hemisphere) results in slightly lower values which are however, not significantly different from those obtained during staring straight ahead. This study adds an electrophysiologic aspect to Kinsbournes's paradigm on gaze position and hemispheric activation. PMID- 2247214 TI - Hemispheric preference and obesity. AB - This study investigated the relationship of hemispheric preference--the tendency to activate one hemisphere rather than the other--and obesity, on 37 right handed, male university students. Hemispheric preference was assessed by the directionality of conjugate lateral eye movements, and the degree of obesity was determined by the body mass index (BMI). The results showed that right hemisphere preferent subjects ("left-movers") are less obese than left hemisphere preferents ("right-movers"). PMID- 2247215 TI - Hemisphere priming through practice in a musical chords task. AB - In a study of selective hemisphere activation, the performance of 30 subjects given either a "local" or "global" priming activity before and after a monoaurally presented chord analysis task was compared with an unprimed control group. The hypothesis was that ear advantage scores on the chords task would show increased left hemisphere involvement following local priming and increased right hemisphere involvement following global priming. The results failed to support this hypothesis. All subjects, however, regardless of priming condition, showed a very strong practice effect represented by a shift from a weak initial left ear (right hemisphere) advantage towards a significant right ear (left hemisphere) advantage (P less than 0.00006). The findings suggest that although the local/global priming activity did not lead to selective hemisphere activation, repeated exposure to the chords task resulted in increased use of analytic left hemisphere processing strategies as subjects became familiar with its processing requirements. PMID- 2247216 TI - Organization of the crossed tecto-reticulo-spinal projection in rat--II. Electrophysiological evidence for separate output channels to the periabducens area and caudal medulla. AB - The previous paper (Redgrave et al., Neuroscience 37, 571-584, 1990) presented anatomical evidence indicating there are at least two largely segregated components of the crossed tecto-reticulo-spinal pathway which project to the periabducens area and caudal medulla. An immediate question arising from this finding is whether tectal cells which project either to the periabducens area or to the caudal medulla have different electrophysiological response properties. An answer to this question would be relevant to the issue of whether different components of the tecto-reticulo-spinal system are specialized for the production of different classes of orienting movement. Accordingly, extracellularly recorded units in the superior colliculus of urethane anaesthetized rats were tested for antidromic activity following electrical stimulation of the periabducens area or the caudal medulla. When antidromic potentials were successfully recorded the sensory properties of the units were tested with a range of unimodal visual, somatosensory and auditory stimuli. The following results were obtained. (i) Tectal cells antidromically activated by stimulation of the caudal medulla were preferentially sensitive to somatosensory stimuli from the perioral region, while cells activated from the periabducens area were more frequently responsive to auditory stimuli. (ii) Tectal fibres activated by stimulation of the caudal medulla had significantly higher conduction velocities than the fibres activated by electrodes in the periabducens region. (iii) More than 90% of antidromically activated cells were located in stratum album intermediale or dorsal stratum profundum. These electrophysiological findings confirm and extend previous anatomical observations which indicate that components of the crossed descending projection of the colliculus may be functionally specialized for the production of different classes of orienting movements. PMID- 2247217 TI - Sodium bromide treatment influences the plasticity of somatosensory responses in the rat cortex as induced by enucleation. AB - Effects of sodium bromide were studied on central neuroplasticity induced by early binocular enucleation. It has previously been found that enucleation on the day of birth, but not later than the first postnatal week, resulted in changes in the occipital cortex, such as the invasion of somatosensory evoked activity into the visual cortex areas. The present results showed that sodium bromide treatment extended at least up to 15 days after birth, the critical period during which somatosensory projections could be modified by visual deafferentation. Together with observations of Frost [J. comp. Neurol. (1981) 203, 227-256; Devl Brain Res. (1982) 3, 627-636], the present results suggest a mutual dependency of visual and somatosensory projection development. The present study is the first demonstration that the critical period of development, during which a specific type of neural plasticity can be induced, may be prolonged by pharmacological means, i.e. by chronic treatment with sodium bromide. PMID- 2247218 TI - The effects of various antidepressant drugs on the fine-structure of neurons of the cingulate cortex in culture. AB - We have examined the effects of antidepressant drugs on the morphology and fine structure of cingulate cortex neurons and synapses in vitro. Dissociated cell cultures from 16-day-old rat fetuses were maintained for up to three weeks in the presence of amitriptyline and desipramine (tricyclic antidepressants) mianserin and citalopram (non-tricyclic antidepressants) or without drugs as controls. Synapses in cultures exposed to amitriptyline and desipramine displayed increased numbers of presynaptic vesicles and more extensive membrane specializations than in control cultures, and increased numbers of coated vesicles both pre- and postsynaptically. In mianserin- and citalopram-treated cultures, synaptic specializations were increased in length, and aggregates of mitochondria at the base of neurites were observed. Our results indicate that long-term exposure to antidepressant drugs results in significant changes in intracellular structure, including changes in synaptic ultrastructure. PMID- 2247219 TI - Synaptic connections of dentate granule cells and hilar neurons: results of paired intracellular recordings and intracellular horseradish peroxidase injections. AB - Simultaneous intracellular recordings were made in the dentate gyrus of rat hippocampal slices, from pairs of the following cell types: granule cells, interneurons located in the granule cell layer, hilar interneurons, and spiny hilar "mossy cells". Granule cells were found to have strong excitatory effects on mossy cells and interneurons. Interneurons inhibited granule cells as well as other interneurons. No synaptic connections from mossy cells onto other cell types were found, within the confines of the slice, using intracellular recording methods. However, at the ultrastructural level, axon terminals of horseradish peroxidase-filled mossy cells were found making synaptic contacts in the hilus on dendrites of interneurons. These studies provide the first step towards determining the functional interactions of the various cell types in the fascia dentata. PMID- 2247220 TI - Cholinergic neurons of the pontomesencephalic tegmentum release acetylcholine in the basal nuclear complex of freely moving rats. AB - Two major systems of cholinergic projection neurons are found within the centrum of the mammalian brain: the basal nuclear complex, projecting predominantly to the cerebral cortex, amygdala, and hippocampus, and the pontomesencephalotegmental network, innervating primarily the thalamus. Neurons comprising the latter network also project to the basal forebrain, but the functional properties of that fiber connection, if any, are unknown. In an attempt to address this issue, the extracellular concentration of acetylcholine was measured in the basal nuclear complex of freely moving rats, both singularly and in combination with lesions and pharmacologic manipulations. Acetylcholine release monitored in the presence of physostigmine sulfate in the basal forebrain was (a) calcium-dependent, (b) increased by systemic scopolamine injection, the rise persisting in the presence of quisqualate lesions of the basal nuclear complex, (c) blocked by tetrodotoxin, and (d) abolished by ablation of cell bodies in the pontomesencephalic tegmentum, which also produced a decrease of choline acetyltransferase activity in the nucleus basalis/substantia innominata region, but not by quisqualate lesions of the basal forebrain. It is concluded from these data that the calcium-dependent release of acetylcholine in the basal nuclear complex (a) is largely axonal in nature, (b) derives substantially from axons of the cholinergic pontomesencephalic tegmentum, and (c) appears to be controlled by presynaptic muscarinic receptors on axon terminals of the latter system. The pontomesencephalotegmental cholinergic complex might thus influence cortical acetylcholine release, in part at least, by means of serial-order cholinergic-cholinergic interactions in the basal nuclear complex. PMID- 2247221 TI - Experimental hemiparkinsonism in the rat following chronic unilateral infusion of MPP+ into the nigrostriatal dopamine pathway--III. Reversal by embryonic nigral dopamine grafts. AB - In a previous study conducted over six months, we demonstrated that 1-methyl-4 phenylpyridinium ion (MPP+) the active metabolite of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, chronically infused (10 micrograms/24 h for seven days) into one median forebrain bundle of the rat can cause long-lasting damage to the nigrostriatal dopamine system. The present study was carried out in animals 18-19 months after MPP+ infusion to determine firstly, if the lesion was indeed permanent and secondly, if embryonic nigral dopamine suspension grafts implanted into the dopamine-denervated neostriatum can reverse the neurochemical and behavioural deficits induced by MPP+. All the animals within the MPP(+)-lesioned group showed robust contralateral and ipsilateral turning in response to apomorphine (0.05 mg/kg) and methamphetamine (2.5 mg/kg), respectively, at each time point of testing. In the grafted animals there was a progressive significant reduction in the number of rotations in response to both apomorphine and methamphetamine over the three-month test period. Autoradiographic analysis of [125I]sulpiride binding to striatal sections showed a 27% increase in dopamine D2 receptor density in the ipsilateral striatum of MPP(+)-lesioned animals. This increase in D2 receptor density was completely abolished by the dopamine grafts so that the D2 receptor density in the grafted striatum was similar to the contralateral striatum of MPP(+)-lesioned animals. This increase in D2 receptor density was completely abolished by the dopamine grafts so that the D2 receptor density in the grafted striatum was similar to the contralateral striatum of the grafted animals or the ipsilateral striatum of control non-lesioned animals. In all the animals of the lesioned and grafted groups there was a complete loss of dopamine neurons in the ipsilateral substantia nigra as demonstrated by tyrosine hydroxylase-immunohistochemistry and in-situ hybridization histochemistry. In all the animals that received nigral dopamine grafts, numerous cells were localized within the grafts which contained tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase mRNA. Moreover, immunohistochemical staining showed a dense network of tyrosine hydroxylase-positive fibres within the grafted striatum. The results of the present study are important in two respects. Firstly, they demonstrate that MPP+ infusions into the rat nigrostriatal dopamine pathway can produce a permanent degeneration of nigral dopamine neurons. Thus, in animals assessed 18-19 months after the initial MPP(+)-lesion there was no significant behavioural or neurochemical compensation with time. Secondly, the results clearly show that embryonic nigral dopamine grafts implanted into the dopamine denervated striatum can reverse the behavioural and neurochemical deficits induced by MPP+. PMID- 2247222 TI - Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. AB - Specific brain sites for the opiate abstinence syndrome syndrome have been elusive to delineate, and the classic overt signs of withdrawal such as wet dog shakes, ptosis and teeth chattering appear to be widely represented in the brain. Using a more general motivational test involving a disruption of operant behavior in dependent rats, the brain site most sensitive to the response disruptive effects of intracerebral administration of the opiate antagonist, methylnaloxonium, was the region of the nucleus accumbens, a site also implicated in the acute reinforcing properties of opiates. This disruption of operant responding was hypothesized to reflect the aversive properties of opiate withdrawal. The present study directly tested that hypothesis by exploring whether intercerebral administration of methylnaloxonium produced aversive stimulus effects as measured by the formation of place aversions. Rats implanted intracerebroventricularly or with bilateral cannulae aimed at the medial dorsal thalamus, periaqueductal gray, ventral tegmental area, amygdala or nucleus accumbens were made dependent on morphine by subcutaneous implantation of two 75 mg morphine pellets. The animals were then subjected to place aversion training by pairing of a distinct environment (one of three arms of a three-armed box with distinct texture, markings and smell) with a single injection of methylnaloxonium intracerebroventricularly or intracerebrally. Results showed that at high doses of methylnaloxonium (1000-2000 ng) all sites produced a place aversion. However, lower doses (250-500 ng) produced a significant brain site selectivity with the region of the nucleus accumbens the most sensitive. Observational measurements taken during the postinjection period with the high dose of methylnaloxonium showed that agitation was particularly observed following methylnaloxonium administration into the nucleus accumbens and periaqueductal gray.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247223 TI - The preoptic area and bed nucleus of the stria terminalis are involved in the effects of the amygdala on adrenocortical secretion. AB - In view of the role of the amygdala in the modulation of adrenocortical secretion we have studied the neural pathways which mediate this response. Changes in plasma corticosterone following medial amygdala stimulation, under pentobarbital anaesthesia, were studied in rats which chronically implanted electrodes in intact and lesioned animals. The rise in plasma corticosterone following amygdala stimulation was inhibited by bilateral lesions of the stria terminals, medial preoptic area, and bed nucleus of the stria terminalis, and to a greater extent by a combined lesion of the latter two structures. The combined lesion also completely blocked the adrenocortical response to olfactory stimulation. These various lesions did not affect, however, the rise in plasma corticosterone following ether stress. These data thus demonstrate that the stria terminalis, preoptic area and bed nucleus of the stria terminalis are involved in the transmission of neural impulses to the hypothalamus which activate adrenocortical secretion. PMID- 2247224 TI - Locomotor recovery in spinal-transected lamprey: role of functional regeneration of descending axons from brainstem locomotor command neurons. AB - In spinal-transected lampreys, locomotor function is restored within a few weeks, and a number of mechanisms could potentially contribute to behavioral recovery. The present study examines the contribution of functional regeneration of descending axons from brainstem locomotor "command" centers to behavioral recovery using both whole animal and in vitro preparations. Under in vitro conditions activation of brainstem locomotor centers could elicit locomotor patterns below a healed transection of the rostral spinal cord. Additional experiments indicated that spinal locomotor networks below a spinal transection could be directly activated by descending axons arising from brainstem neurons. In contrast, mechanosensory inputs and regenerated spinal neurons did not contribute significantly to the initiation of locomotor activity below a spinal lesion. Regenerated descending axons from large reticulospinal Muller neurons did not contribute significantly to the recovery of locomotor function. These results suggest that functional regeneration of descending axons from neurons in brainstem locomotor command centers contribute significantly to the recovery of locomotion following spinal cord transection. This is the first demonstration in a vertebrate of functional regeneration of descending command axons which can initiate locomotion. PMID- 2247225 TI - Acupuncture and diffuse noxious inhibitory controls: naloxone-reversible depression of activities of trigeminal convergent neurons. AB - Recordings were made from convergent neurons in trigeminal nucleus caudalis of the rat. These neurons could be activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields on the ipsilateral part of the muzzle. Percutaneous application of suprathreshold, 2 ms square-wave electrical stimuli to the centre of the excitatory field resulted in responses to A- and C-fibres being observed. The effects on these responses of manual acupuncture performed by a traditional Chinese acupuncturist at the "Zusanli" point on the right hindlimb were compared with the effects induced by acupuncture applied at a non-acupoint, next to "Zusanli". In addition, the effects of acupuncture were compared with the inhibitory effects evoked by noxious thermal stimulation of the left hindlimb on the responses of the same neurons. This last type of inhibition has been described previously by our group and termed diffuse noxious inhibitory controls. Acupuncture, either applied at "Zusanli" or at a non-acupoint and noxious thermal stimulation induced similar strong inhibitory effects on the C-fibre-evoked responses of trigeminal convergent neurons (77.9 +/- 4.4%; 72.5 +/- 4.6% and 78.5 +/- 3.6% inhibition, respectively) and these inhibitions were followed by long-lasting aftereffects. In addition, both the acupuncture- and noxious thermal stimulation-evoked inhibitions were significantly reduced by systemic naloxone (0.4 mg/kg, i.v.). Since the antinociceptive effects elicited by acupuncture (i) had a similar magnitude and time-course to those evoked by noxious thermal stimulation, (ii) exhibited a lack of topographical specificity and (iii) involved an opioidergic link, we would suggest that, at least in our experimental conditions, acupuncture manoeuvres trigger the neuronal mechanisms involved in diffuse noxious inhibitory controls. PMID- 2247226 TI - Calcium-binding proteins calbindin and parvalbumin in the superficial dorsal horn of the rat spinal cord. AB - Neurons containing the calcium-binding proteins, calbindin or parvalbumin, were studied by immunohistochemistry in the superficial dorsal horn of the rat spinal cord. Calbindin-containing cells were found in laminae I, II and III, being more abundant in laminae I and II. Some of the neurons in lamina I containing calbindin projected to the supraspinal area. Parvalbumin-containing neurons were mainly distributed in laminae IIi and III. Calbindin and parvalbumin were not detected in the same cells. Some 75% of the neurotensin-like immunoreactive neurons contained calbindin, which corresponded to 13% of the calbindin containing neurons. Calbindin was sometimes found in the same cells with substance P, enkephalin or somatostatin but less frequently (44-46% of the peptide-containing neurons). Parvalbumin was not found together with these peptides. Electron microscopy showed that the immunoreactive products of calbindin or parvalbumin were mostly in the dendrites or cell bodies. Immunoreactive axon terminals were relatively few. In rhizotomized animals, neurons containing one of these proteins in laminae II and III were found to receive direct inputs of primary afferent fibers. These findings indicate that neurons containing these two proteins belong to different subpopulations of dorsal horn neurons. They may be important in primary afferent processing. PMID- 2247228 TI - Indications for thymectomy in myasthenia gravis. AB - Fifty-six board-certified neurologists with interest and expertise in myasthenia completed a survey of indications for thymectomy in myasthenia gravis. Thymectomy was advocated for virtually all patients with thymoma, for a variable subset of patients with generalized myasthenia without thymoma, and occasionally for selected patients with disabling ocular myasthenia. PMID- 2247227 TI - Inherited human prion diseases. PMID- 2247229 TI - Charles Bell's description of the phantom phenomenon in 1830. PMID- 2247230 TI - Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2 13.3 (SMA 5q). AB - We made phenotypic analysis of 14 families with spinal muscular atrophy (SMA) linking to chromosome 5q11.2-13.3 (SMA 5q), and 2 that may not map to this locus, to assess clinical symptoms among SMA families known to result from mutation at the identical gene/locus. Although the current number of families is still small, the correlation of clinical phenotype and molecular genotype supports 2 observations. First, SMA mutations at the 5q locus present with a broad continuum of clinical abnormalities, and 2nd, the single clearly unlinked family presents with an unusual phenotype characterized by relatively late onset and early death. Thus, there are as yet no unambiguous cases of typical SMA families that are clearly unlinked to the locus at 5q-ie, no clear cases of nonallelic heterogeneity. Analysis of SMA 5q families supports the view that, with certain exceptions, there is little phenotypic intrafamilial variability. When families were ranked by severity of disease there was a strong correlation with age of onset. Onset within the 1st few months was associated with early death, but not in all cases. With rare exception, onset after 1 year of age was associated with less severe disease and greater longevity. PMID- 2247231 TI - Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome. AB - Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG. PMID- 2247232 TI - Conjugal temporal arteritis. AB - We report the simultaneous occurrence of biopsy-proven temporal arteritis in husband and wife. Serologic and viral studies were negative, including viral culture of the wife's temporal artery. The concurrent incidence of giant cell arteritis in a married couple would suggest a common exogenous exposure. PMID- 2247233 TI - Internuclear ophthalmoplegia in the Chiari type II malformation. AB - We describe 3 cases of Chiari type II malformation presenting with bilateral internuclear ophthalmoplegia (INO). Although prominent, the INO was not an isolated sign in any of the patients; superimposed abduction paresis was present in 2, and deficits in smooth pursuit, optokinetic nystagmus, and vestibulo-ocular responses were present in 3. Two had hydrocephalus: 1 was clinically unchanged without therapy after 5 years; the other did not improve with shunting. Findings in our 3 patients, along with the 4 previously reported, confirm that INO is 1 manifestation of widespread brainstem or cerebellar dysfunction. Its origin is probably multifactorial, related to hydrocephalus, vascular compromise, direct neuronal distortion, or congenital neural malformation. PMID- 2247234 TI - Sensory visual testing in idiopathic intracranial hypertension: measures sensitive to change. AB - Management decisions in idiopathic intracranial hypertension (IIH; pseudotumor cerebri) are based on the presence and change of visual loss. To study this change, we evaluated tests of sensory visual function over time. We used the results of the right eye of 19 patients whose clinical status improved (decrease in papilledema grade), and compared the outcome measures of the initial and final examinations. Contrast sensitivity testing showed significant improvement in the middle and high spatial frequency targets. Snellen acuity and color tests did not change significantly over the same period. Both Goldmann and automated visual field grade significantly improved from the initial to the final visit, while the presence of a defect on confrontation visual fields did not. Numerical analyses of automated perimetry thresholds also showed significant improvement. Generalized loss, most pronounced on the nasal side of the visual field, was present on the initial examination. Generalized improvement followed, least in the central and inferior paracentral areas. Patients with IIH should be followed with contrast sensitivity testing and perimetry using a disease-specific strategy. PMID- 2247235 TI - Deteriorating ischemic stroke: risk factors and prognosis. AB - To determine a risk profile of deterioration in cerebral infarction of less than 8 hours' duration, we studied prospectively a series of clinical and radiologic data in 98 patients. We evaluated the Canadian Neurological Scale Score and Barthel index during a follow-up period of 3 months. There was deterioration in the 1st 48 hours in 40.8% of the patients. High systolic blood pressure, elevated blood sugar concentration at admission, and carotid territory involvement were independently related with deterioration in the logistic regression analysis. Death occurred in 35% of the patients with deteriorating infarcts and in 8.6% of those with stable infarcts. At the end of the study, functional capacity was lower in those with deteriorating infarcts, but the 2 groups improved in parallel from the 4th day onward. PMID- 2247236 TI - Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. AB - Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity. PMID- 2247237 TI - Infantile CNS spongy degeneration--14 cases: clinical update. AB - We studied 14 Arab infants with infantile spongy degeneration, 13 of whom were products of consanguineous marriages. They presented in infancy with macrocephaly, poor visual behavior or blindness, and axial hypotonia with appendicular spasticity. Brain CT and MRI showed diffuse symmetric leukoencephalopathy, even before neurologic symptoms. There were relatively normal EEGs. The visual evoked responses (P100) were either absent or delayed early in the course. The brainstem auditory evoked responses showed milder abnormalities, with loss of later components before the earlier ones. Deficient aspartoacylase activity in cultured fibroblasts or brain biopsy confirmed the diagnosis in all patients. PMID- 2247238 TI - Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. AB - We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible. PMID- 2247239 TI - Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability. AB - We examined the relationships between muscle force and both phosphate and hydrogen ion concentrations in muscles with differential fatigability and in different types of exercise. We measured force and 31phosphorus nuclear magnetic resonance spectra from the tibialis anterior (a slow-contracting, fatigue resistant, postural leg muscle) during a sustained maximum contraction (anaerobic exercise) and during intermittent contractions (aerobic exercise). We observed similar relationships between the decline in muscle force during fatigue and changes in both phosphate and hydrogen ion concentrations during both aerobic and anaerobic exercise in tibialis anterior. Furthermore, these relationships were similar to those previously observed in the adductor pollicis. The demonstration of constant relationships between muscle contraction force and metabolism under different exercise conditions and in muscles of different function supports the view that both phosphate and hydrogen ions are important regulatory factors in the fatigue of human muscle. PMID- 2247240 TI - The utility and generality of Mini-Mental State Examination scores in Alzheimer's disease. AB - The present study sought to evaluate the validity and generality of the Mini Mental State Examination (MMSE) and its subsection scores. We gave the MMSE and other neuropsychological tests to 51 patients with probable Alzheimer's disease. On the basis of correlational and factor analyses, overall performance on the MMSE proved to have good concurrent validity with other comprehensive neuropsychological assessment instruments. However, the MMSE subsections should not be viewed as highly specific measures of cognition or memory. PMID- 2247241 TI - Sensorineural hearing loss: a reversible effect of valproic acid. AB - We report 2 patients over the age of 70 who, while on valproate (VPA) for complex partial seizures, developed sensorineural hearing loss. Following discontinuation of VPA for nonaudiologic reasons, the patients reported improved hearing which was confirmed by audiometry. These findings represent VPA-induced sensorineural hearing loss, possibly in preexisting presbycusis. PMID- 2247242 TI - Large cystic optic glioma. AB - A 5 1/2-year-old boy developed a huge cyst in his chiasmal glioma 4 years after radiation therapy. The cyst produced obtundation but was successfully treated. PMID- 2247244 TI - Presence of normal dystrophin in Tunisian severe childhood autosomal recessive muscular dystrophy. PMID- 2247243 TI - Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis. AB - We report 2 patients with Guillain-Barre syndrome (GBS) following Campylobacter jejuni enteritis. Electrophysiologic studies indicated that the predominant process was axonal degeneration of motor nerves, and clinical recovery was poor. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that the sera from both patients contained high titers of IgG antibody against GM1 ganglioside. These cases may represent a subgroup of GBS as acute axonal polyneuropathy following C jejuni enteritis associated with anti-GM1 antibodies. PMID- 2247245 TI - Persistent dystonia associated with buspirone. PMID- 2247246 TI - Dietary weight reduction and seizures. PMID- 2247247 TI - Essential leg tremor. PMID- 2247248 TI - Neck manipulation and stroke. PMID- 2247249 TI - [Noninvasive hemodynamic monitoring via the integration of data obtained by ECG, aortic flow by Doppler esophageal probe and by finger plethysmography]. AB - The aims of this work are to describe the general and technical characteristics of a new device for the noninvasive monitoring of patients in intensive care and during general anaesthesia, and the results concerning the reliability of this method. An ultrasonic esophageal probe and an echo-Doppler device have been used to obtain continuous data of the aortic diameter and of blood velocity. Aortic output is calculated automatically. This method, together with other non-invasive monitoring techniques (blood pressure, heart rate, rhythm and cardiac conduction), gives on the one hand the data of aortic output, systemic peripheral resistance and stroke volume; on the other, through a computerized elaboration, the systolic time intervals (PEP pre-ejection period, LVET left ventricular ejection time, QS2 electromechanical systole, PEP/LVET ratio of PEP to LVET). The validation of STI data, has been obtained through 125 comparative measurements for each of the three parameters. The data obtained through the aortic velocity waveform in descending aorta (pulsed Doppler) have been compared with those obtained through the aortic pressure waveform (intra aortic catheter). The correlation was: PEP 0.92, LVET 0.95, QS2 0.93. The clinical application of this method supplies data concerning cardiac load, after-load and indirectly cardiac pre-load. This non-invasive procedure gives us a continuous measurement of hemo dynamic situation, which allows the physician to plan and evaluate the therapeutical efficacy. Finally new pathologic events may be opportunely faced. PMID- 2247250 TI - [Anesthesia, awareness and wakefulness]. AB - Drugs used in anesthesia do not always produce the expected neurophysiological results. By studying those cases in which the reappearance of intraoperative awareness is most common, an attempt was made to estimate how many and which levels of cerebral function could be identified. Four levels were recognised: awareness with or without memory, and wakefulness with or without dreams. These conditions are related to greater or lesser cortical activity. They can be identified using Tunstall's technique and by carefully interviewing the patient immediately after the operation. PMID- 2247251 TI - [Total intravenous anesthesia with propofol vs. propofol/N2O anesthesia]. AB - The authors have compared two groups of 31 patients each, undergone an anaesthesia with propofol-O2/N2O (group I) and propofol-O2/air (group II). The average anaesthetic dosage and the neuromuscular recovery time have been valued, keeping constant the dose of analgesic. The average consumption of propofol (except the inductive dose of 2 mg/kg) was 7.41 +/- 1.71 mg/kg/h in group I, and 7.47 +/- 1.76 in group II (p = 0.88; not significant) and the neuromuscular recovery time 56.12 +/- 34.55 m' and 49.48 +/- 40.50 m' respectively (p = 0.53; not significant). The cardiocirculatory parameters have been compared at the time of induction, surgical incision and for all the operation time, reporting every undesired effect. The awakening has been monitored until 15 m' from the interruption of propofol infusion. The data obtained don't permit to observe significant differences with regard to analgesia, neuromuscular block and awakening time. Therefore the authors put the question of the real necessity to use nitrous oxide, when it has utilized an efficient intravenous anaesthetic as the propofol has proved to be. PMID- 2247252 TI - [Anesthesia and the chemotaxis of neutrophilic granulocytes in newborn infants]. AB - The authors investigated the modifications of neutrophil chemotaxis and cortisol plasma levels in the newborn delivered by cesarean section or vaginal delivery. Chemotaxis turned out to be higher in the group undergoing cesarean section, while cortisol was lower in this group. The increased activity of neutrophils can be explained with the lessened inhibitory effect of endogenous steroids and with the stimulating action of nitrous oxide. PMID- 2247253 TI - [The relationship between ligation of the ductus arteriosus and intracranial hemorrhage in preterm infants]. AB - Surgical closure of patent ductus arteriosus (PDA) and perioperative time have been proposed as conditions of increased risk of peri-intraventricular hemorrhage (PVH-IVH) in preterm infants. We examined by pre- and postoperative ultrasound (US) scan 15 low birth-weight neonates who underwent PDA ligation within the first two weeks of life. They were assessed with regard to clinical state, perioperative management and development of PVH-IVH. Fourteen did not show onset or extension of intracranial hemorrhage in the immediate postoperative period. One patient developed a wide III grade IVH in the 24 perioperative hours. His conditions were particularly severe, suggesting that many factors such as acidosis, hypoxia, hypercapnia and hypotension might have combined to lead to hemorrhage. We conclude that PDA ligation is not likely to increase the risk of PVH-IVH per se. PMID- 2247254 TI - [Hemofiltration and dialysis in a case of rhabdomyolysis]. AB - The effect of CAVDH was evaluated in a patient with rhabdomyolysis due to extreme low temperature and also to carbon monoxide poisoning. Since renal failure im myoglobinuria has a relatively good prognosis, we recommend in this case the use of a soft technique such as continuous arteriovenous hemofiltration with dialysis. PMID- 2247255 TI - [An anaphylactic reaction to succinylcholine. A clinical case]. AB - A case of severe anaphylactic reaction provoked by suxamethonium during the induction of general anaesthesia is reported. Diagnosis of reaction and the trigger effect of suxamethonium was identified by intradermal testing. Diagnosis of anaphylactic reaction was confirmed on serial blood estimations of IgE and C3 C4 of complement fractions. PMID- 2247257 TI - [Metachronous tumors of the large intestine. The anatomicoclinical considerations]. AB - The paper analyses the results of a large number of patients operated for large intestine carcinoma who then underwent a postoperative endoscopic follow-up to assess the number of metachronous tumours. The anatomicoclinical characteristics of the latter are discussed. PMID- 2247256 TI - [A decade of experience in rescreening for colonic cancer in a working population]. AB - The authors carried out a screening on a population of metallurgical and mechanical workers, repeated five times in ten years, in order to have early diagnosis of colon-rectum's neoplasia by means of Hemoccult test. They used the GOICC's (Gruppo Operativo Italiano Cancro del Colon) methodology and took under consideration 726 workers (442 men and 264 women between 40 and 60 years old), on the whole 1094 tests. They had considered the repetition frequency of a test in any single worker in relation with sex and age. Considering this group of people they realized that a greater sensibilization could be referred to people under 50, male (the latest data is statistically significant). The compliance increased due to a greater sensibilization and aggregation of a group that can be considered "homogeneous". On the basis of these results, the usefulness of this kind of preventive test is suggested. PMID- 2247258 TI - [Gallbladder carcinoma. The clinical and echographic aspects in 3 cases]. AB - Gallbladder carcinoma is difficult to diagnose in its early stage due to the nonspecificity of various characteristics. The authors describe 3 cases of gallbladder carcinoma. Diagnostic utility of ultrasonography in primary carcinoma of the gallbladder and diagnostic problems in the differentiation from inflammatory diseases are reported. PMID- 2247259 TI - [A gastric leiomyoma of conspicuous size. A case report]. AB - The authors describe a large gastric leiomyoma with prevailing subserous growth. Conventional X-ray examination and endoscopy failed to diagnose the lesion properly. On the contrary, with CT it was possible to hypothesize the existence of leiomyoma with the correct definition of the outline of the lesion. PMID- 2247260 TI - [An aneurysm of the inferior pancreaticoduodenal artery: a surgically treated case]. AB - Aneurysms of the lower duodenal pancreatic artery are an extremely rare dilatative arterial pathology. Diagnosis is often difficult and rupture is a frequent clinical evolution; surgical therapy, especially when rupture has already occurred, entails a high risk of operative mortality. A case is described of aneurysm of the lower duodenal pancreatic artery which was treated by elective surgery with good results. PMID- 2247261 TI - [The current physiopathological, diagnostic, clinical and therapeutic considerations of peptic ulcer. A comparison between traditional and modern therapeutic methods]. AB - The authors, keeping in mind their clinical, diagnostic and therapeutic experience on ulcerous gastric and duodenal pathology, underline the effectiveness of the traditional antacids as well as that of the modern up-to date antisecretory and cytoprotective agents. After having put into evidence the causes that can provoke peptic ulcer not excluding that of iatrogenic and their probable aetiopathogenetic mechanism and having hinted at another pathology that uses the same therapeutic remedies, the gastro-oesophagus reflux, they discuss in detail the active principles used in the gastric or duodenal pathology, the possible side and/or secondary effects that in the long run are determined when using only the modern therapy with the usual antacids. Therefore, they hope that these therapies are used after carefully considering the general clinical and anatomicopathologic situation of the lesion that must be created. PMID- 2247262 TI - [Changes in the blood zinc in the irritable bowel syndrome: a preliminary study]. AB - Having outlined the important role played by zinc in the human metabolism and the alteration which may occur as a result of a zinc deficit, the paper reports a study of 50 patients affected by irritable bowel syndrome. Two subgroups have been identified (Ac and Ad), characterised by reduced blood zinc [correction of zinchemia] and increased fecal excretion of zinc. This finding suggests that the syndrome has a multifactorial pathogenesis and that over time it may follow a different pattern in the different subgroups. PMID- 2247264 TI - [The diagnostic significance of the blood chemical and histological parameters in a group of chronic alcoholics with hepatopathy]. AB - Different hematochemical parameters using a histological sample (hepatic needle biopsy) were compared in patients affected by alcoholic liver diseases. In conclusion, the importance of hepatic needle biopsy is confirmed in the definitive diagnosis of this pathology. PMID- 2247263 TI - [A comparative evaluation of computerized diagnostic decisional support in gastroenterology in relation to typical clinical pictures]. AB - On the basis of the results obtained in a previous perspective comparative study aimed to compare the diagnostic accuracy of a computerized diagnostic decisional support in gastroenterology with that of non-specialist physicians, the Authors have carried out a retrospective study, based on the same series and on the same results, but disaggregating the global comparisons according to the feature of the clinical presentations. The latter were therefore classified by independent gastroenterologists as "typical", "atypical", or "borderline", and for each group the difference of diagnostic accuracy between program and physicians was again evaluated. Even if the program proved more accurate in all groups, the greatest difference was observed in the "borderline" group which the Authors claim to include the kind of presentation which more than any other needs a decisional aid. This should suggest a possible useful implementation of the system in daily clinical practice. PMID- 2247265 TI - [Biliary lithogenic factors in the course of alcoholic liver cirrhosis]. AB - The ultrasonographic features of cholelithiasis in alcoholic cirrhosis indicate a greater density of lyme bile and the presence of micropolylithiasis. It is also correlated with the high levels of unconjugated bilirubinemia. Lithogenesis may be related to some stages of the disease. PMID- 2247266 TI - [Endoscopic sclerotherapy and upper digestive hemorrhages. Personal experience]. PMID- 2247268 TI - Update on epilepsy care. PMID- 2247269 TI - Hospital governance: nurse trustee vis-a-vis nurse executive. PMID- 2247267 TI - [Environmental risk factors in the pathogenesis of peptic ulcer. The role of cigarette smoke]. AB - Smoking habit has been evaluated in 108 patients with gastric or duodenal ulcer diagnosed by endoscopy and in a control group of 147 endoscopically normal subjects. We found a positive association for both the gastric and duodenal ulcer (relative risk of 3.5). Furthermore, an increasing risk was associated both with the duration of smoking and with the amount of cigarettes smoked daily. Conversely, no significant association was demonstrated between peptic ulcer and the more os less precocious age at starting smoking or with the nicotine and tar content of the cigarettes usually smoked. Among ex-smokers, an increasing risk (relative risk of 2.0) was observed for gastric ulcer only. PMID- 2247270 TI - The surgical nurse's liability. PMID- 2247271 TI - Three simple rules. PMID- 2247272 TI - Women's Health Equity Act of 1990. PMID- 2247273 TI - How to survive the next decade. PMID- 2247274 TI - Prompt service: a factor in patient satisfaction. PMID- 2247275 TI - The nurse manager resource peer: Part II. PMID- 2247276 TI - Theory Z: "magic potion" for decentralized management? PMID- 2247278 TI - Preoperative outpatient education in the 1990s. PMID- 2247277 TI - Alternatives to mouth-to-mouth rescue breathing. PMID- 2247279 TI - Nursing in 2001: are you ready? PMID- 2247280 TI - Surviving organizational change. PMID- 2247281 TI - Nursing care for unhealthy hospital bureaucracies. PMID- 2247282 TI - A team approach to psychiatric care. PMID- 2247283 TI - Maria's choice. PMID- 2247284 TI - Demand for trained professionals increases educational interests. PMID- 2247285 TI - Demand for safety in healthcare grows even as institutions face budget cuts. PMID- 2247286 TI - Biology of retroviruses. Detection, molecular biology, and treatment of retroviral infection. AB - Although human retrovirology can trace its roots to the early part of this century, it has been within the last decade that the field has seen its greatest advances, including the description of the first human retroviruses, HTLV-I, and the subsequent discovery of HTLV-II and the AIDS retroviruses, HIV-1 and HIV-2. The growth this field has undergone in recent years would not have been possible had it not been for key advances in the fields of cell biology, immunology, biochemistry, and molecular biology. Nowhere has this been more evident than in the description of HIV as the etiologic agent of AIDS. In the relatively short time since the disease was initially described, the agent responsible has been isolated, much of its complex biology has been defined, and a drug that helps combat it has been licensed for use. The rapidity with which these events have transpired is largely unprecedented. There remain many unanswered questions regarding HIV and AIDS, and there still is no effective vaccine or cure. Significant questions regarding the immune response to HIV and the HIV response to immune or chemotherapeutic challenge, the establishment and maintenance of HIV latency, and the all-important mechanisms of HIV cytopathicity remain unanswered. It is clear that HIV offers no easy answers, and that significant work remains to be done before death from AIDS can be halted. PMID- 2247287 TI - HIV disease in pregnancy. PMID- 2247288 TI - Epidemiology of human immunodeficiency virus infection in women in the United States. AB - From 1981 to 1989, the number of women with HIV infection and acquired immunodeficiency syndrome (AIDS) increased rapidly. Most women were infected through intravenous drug use or sexual contact with an infected man. Most children were infected through mother-to-infant transmission during pregnancy or delivery. Available data suggest that the rapid increase in the number of women with AIDS will continue for at least the next few years. PMID- 2247289 TI - AIDS. Natural history and prognosis. AB - Infection with HIV results in a chronic, persistent infection that usually progresses slowly from an asymptomatic state to full-blown AIDS. AIDS remains a lethal disease with no effective cure. A great deal of information has been learned in the past decade, yet many questions remain unresolved. Much more research is needed into the conditions surrounding the perinatal transmission of HIV. Many women who give birth to a child with AIDS are themselves asymptomatic for HIV infection during pregnancy and at delivery; thus, routine voluntary prenatal HIV screening programs must be instituted in areas of high seroprevalence. Such screening programs must provide pretest and post-test counseling with consent and confidentiality. Seroprevalence studies conducted during the perinatal period or at birth using newborn blood samples will provide important epidemiologic data for further research investigations as well as continued estimates of the prevalence of HIV infection. Currently, there is no formal reporting system for HIV infection, only for the clinical expression of AIDS. There may be a need to develop a centralized reporting unit for HIV infection. As the epidemic continues and the true prevalence rates are determined, additional resources for public health care, housing, insurance, and foster care for children will be needed. The number of women who are infected is increasing at an alarming rate. Every opportunity to increase public awareness about the AIDS epidemic and modes of transmission must be exploited if we are to impact on the spread of HIV infection. Prospective studies of pregnant HIV positive women and pediatric follow-up can provide a wealth of data about AIDS and disease progression in both the mother and the infant. Even if some children do not develop AIDS, the possibility of permanent effects of in utero exposure to the virus still exists. At what exact point in gestation does infection occur? Can infection be prevented or delayed with current chemotherapeutic protocols? Even if a cure or vaccine is developed in the near future, the impact of this deadly virus will have repercussions for many years to come. PMID- 2247290 TI - Primary care of women infected with the human immunodeficiency virus. AB - AIDS is the leading cause of death among women aged 25 to 34 years in New York City. Gynecologic care should be directed toward early identification and aggressive treatment of infectious and neoplastic processes that may take a more fulminant course in immunosuppressed women. Dealing with women's contraceptive needs highlights the problem of preventing sexually transmitted diseases through contraceptive technology. Public health policies and recommendations will be of no avail without an educated and supportive medical community. PMID- 2247291 TI - Human immunodeficiency virus education and screening of prenatal patients. AB - Prenatal HIV education and testing requires access to many resources and is demanding of time and personnel. Properly trained sympathetic on-site counselors are essential. Such personnel may combine this role with other tasks but should have the time necessary to commit to individualized HIV counseling. High-quality laboratory facilities should be available. Ready access to psychiatric professionals, social service supports, clergy, internal medicine, pediatric primary care, and infectious disease consultation or referrals needs to be available and integrated into all prenatal screening programs. Obstetrician/gynecologists at all levels should seek access to and support for these necessary though resource-intensive programs and work toward extension of such programs to all women of childbearing age. PMID- 2247292 TI - Influence of human immunodeficiency virus infection on reproductive decisions. AB - This article discusses the role of the practitioner in the pregnancy decision making process of the HIV-infected woman. Literature on women's decisions is reviewed, and variables that influence decisions are discussed. The author concludes that HIV infection does not have a significant impact on pregnancy decisions. Other cultural and psychosocial variables may have more importance. PMID- 2247293 TI - Role of the placenta in perinatal transmission of HIV. AB - The role of the placental tissue in the perinatal transmission of HIV is still far from being understood. Significant data regarding transplacental infection have been collected, but differences in technique have led to controversy. It appears clear that many Hofbauer cells are CD4+ and can become infected with HIV. Less certain but probable is infection of trophoblasts themselves. Whether infection is CD4 mediated or via cell-cell fusion is not established. Transplacental traffic of virus and cells remains a little-studied possibility. Further data are needed regarding the fascinating concept of the placenta as a modulator of infection. PMID- 2247294 TI - Human immunodeficiency virus infection in pregnancy. AB - Among an estimated 1 million to 1.5 million Americans infected with HIV, about 10 per cent are women. Moreover, almost 30 per cent of HIV infection among women is acquired through heterosexual activity. Therefore, the average obstetrician/gynecologist is not sheltered from dealing with HIV. This article offers guidelines for caring for HIV-infected pregnant women during antepartum, intepartum, and postpartum phases. PMID- 2247295 TI - HIV infection. Managing exposure risks for the obstetrician/gynecologist. AB - Human immunodeficiency virus infection in women is geographically widespread throughout the US. Infected blood is the single most important source for HIV transmission in the health care setting. Occupationally acquired HIV infection appears to be an uncommon event, with prospective studies thus far reporting an incidence of 0.6 per cent or less. Strategies for preventing transmission of HIV infection in an obstetric/gynecologic setting are a matter of appropriate barrier protection, good infection control technique, and a large measure of common sense. PMID- 2247297 TI - On the evaluation of the corneal epithelial surface by scanning electron microscopy. AB - A comprehensive and objective survey is presented of the use of the scanning electron microscope from 1967 to 1989 to assess the characteristics of the corneal epithelial surface in the rabbit and other vertebrates. The technique shows the corneal surface as a mosaic of cells that are very heterogeneous with respect to character (light, medium, and dark electron reflexes), size (small, medium, and large), and shape (angular or rounded), yet the numerous published micrographs of normal corneas show substantial differences. The reasons for these differences are discussed using examples of 50 to 15,000 x magnification micrographs of rabbit corneas within the context of the basic principles of glutaraldehyde-based fixation of biological tissues for electron microscopy. The qualitative similarities between the scanning electron microscope image and the in vivo reflected light microscope (specular microscopy and CONFOCAL microscopy) image are reviewed and discussed. PMID- 2247298 TI - Measurement of posterior corneal surface toricity. AB - We describe a method in which posterior corneal surface toricity can be determined by photographing catoptric (Purkinje) images in three fixed meridians simultaneously using infrared light sources. Keratometry, the comparison of anterior and posterior corneal catoptric (Purkinje) images and pachometric results, are applied to three meridional analysis equations, allowing the posterior corneal surface to be described in spherocylindrical form. The technique is evaluated on five subjects with anterior corneal radii varying from 7.11 to 8.52 mm. PMID- 2247296 TI - Human immunodeficiency virus infection, women, and pregnancy. Ethical issues. AB - Should women of childbearing age be screened for the presence of infection with the human immunodeficiency virus? If infected, should they be instructed not to become pregnant or not to bear children? Should pregnant women and their offspring be included in research protocols that explore ways to prevent or treat perinatally acquired HIV disease? This article examines ethical controversies related to HIV screening, counseling, and research and suggests that resolutions may come from achieving greater clarity about the ultimate goals of obstetric and gynecologic care. PMID- 2247299 TI - Silicone-acrylate contact lenses for myopia control: 3-year results. AB - One hundred myopic children between the ages of 8 and 13 years were fitted with Paraperm O2plus silicone-acrylate contact lenses. After 3 years of lens wear, the mean increase in myopia for the 56 subjects remaining in the study was 0.48 D (+/ 0.70) D as compared with 1.53 (+/- 0.81) D for a group of spectacle-wearing myopes matched for initial age and initial refractive error. The mean change in corneal refracting power for the contact lens wearers was a decrease (corneal flattening) of 0.37 (+/- 0.32) D. Assuming that little or no corneal change would have occurred in the absence of the contact lenses, we may conclude that corneal flattening (as measured by the keratometer) accounts for less than half of the effect of contact lenses in controlling myopia progression. A possible explanation for this disparity is that although the keratometer provides a valid measurement of corneal refracting power for a "normal" cornea, it fails to provide a valid measurement for a cornea that has been flattened by wearing a contact lens. PMID- 2247300 TI - The component of gaze selection/control in the development of visual acuity in children. AB - Visual acuity was tested for 180 eyes of 90 children in four age groups using three types of test charts. Subjects read the same 10 high-contrast letters in Snellen (line) format, as isolated-letter flash cards, and as repeat-letter flash cards. Group mean line and group mean isolated-letter acuity showed similar progressive improvements with age. A subgroup of 24 of 50 eyes of 4- to 5-year olds (15 of 25 subjects) and 3 of 50 eyes of 6- to 7-year-old (2 of 25 subjects) had low Snellen acuity. Of this low-acuity subgroup of 27 eyes, 10 scored above average for their age group on the repeat-letter chart. We concluded that abnormal lateral interactions were not the explanation for the immaturity of Snellen acuity in these 10 eyes. We suggest that an important factor in the low acuities of these 10 eyes is delayed development of the selection and/or control of gaze direction. Some eyes with excellent Snellen acuity showed high crowding. For example, there were five such eyes in the oldest group. We suggest that the excellent acuities of at least two of these eyes are limited by minor inaccuracies in gaze selection and/or control rather than by lateral interaction. PMID- 2247301 TI - Stability of retinal correspondence during divergence: evaluation with afterimages and Haidinger brushes. AB - Retinal correspondence has been described as invariant during normal binocular vision. However, there is substantial evidence that casts doubt on this interpretation and implies that retinal correspondence varies under certain conditions. This article reports the results of two experiments that appraise the stability of correspondence during fusional vergence in persons with normal binocular vision. In the first experiment, afterimages stimulated vertically corresponding retinal meridians prior to divergence. Three of six subjects gave data that indicated a change in the afterimage alignment significantly different from chance. The second experiment determined corresponding retinal areas with Haidinger's brushes. When divergence was maximally maintained, all six subjects who could appreciate the low-contrast Haidinger's brushes on the randomdot background saw two brushes while stereopsis and fusion remained present. Increases in plus lens power increased estimated brush separation. PMID- 2247302 TI - Birefringent multifocal lenses: theory and application to the correction of refractive error. AB - Light passing through birefringent materials experiences two indices of refraction, and lenses made of or incorporating birefringent materials will therefore exhibit two focal points. The optics of birefringence are summarized, and their application to lenses is described. Prototype lenses based on these principles were produced, and the bifocal effect was observed. Multifocal lenses based on these principles have numerous uses, including contact and intraocular lenses. PMID- 2247303 TI - Statistics notebook: entry I.K, the normal (or Gaussian) distribution. PMID- 2247304 TI - [The Ekbom symptom in schizophrenic psychoses]. AB - In connection with their schizophrenic cases, the authors analyse the nosological and psychodynamical characteristics of the phenomenon described by Ekbom. They emphasize the interaction between the psychotic process and object losses, which can be observed in the formation of secondary symptoms. PMID- 2247305 TI - [Hypoxic myoglobinemia in severe neonatal disorders of adaptation to extrauterine life]. AB - In two series of newborns needing intensive care the presence, the degree and the prognostic value of myoglobinaemia was examined. In series I. of hypoxic newborns the myoglobinaemia was present even in infants requiring less than 60% O2 therapy. The serum myoglobin value was significantly higher in cases needing oxygen therapy over 60% oxygen. This was most pronounced in the critically severe and progressive cases. In series II. of 34 consecutive cases of hypoxic newborns exceeding 7 nM/l proved to have a prognostic value indicating critically severe course or fatal outcome of the disease. The myoglobinaemia observed in the present study may explain the effectivity of the peritoneal dialysis therapy introduced previously by us in severe hypoxic newborns. This possibility was supported by further observations on the transperitoneal passage of myoglobin in 4 renal hilus ligated and peritoneally dialyzed newborn piglets. In conclusion, early detection of the elevated myoglobinaemia in severely hypoxic newborns has a definite prognostic value and its degree can be used in the indication of peritoneal dialysis. PMID- 2247306 TI - [Vaccine therapy of malignant tumors]. AB - Vaccine therapy of neoplasms increases anti-tumor immune responses by enhancing the immunogenicity of tumor cells. One possible way of vaccine therapy is treatment with live apathogenic virus vaccines, in particular with Newcastle disease virus and other apathogenic avian viruses. Frequent regression of tumors and subjective improvement by vaccine therapy of patients may be explained by: a) infection of tumor cells by the virus and so enhancing their immunogenicity, b) activation of cells of the immune system, increased production of interferons, tumor necrosis factor-alpha and other cytokines, c) increased production of ACTH and beta endorphin by monocytes and lymphocytes resulting in an improvement in the general well-being. According to the previous results and the experimental data, extended trials with avian virus vaccines seem to be promising. PMID- 2247307 TI - [The incidence of iron deficiency in Hungary among children aged 4-6 years]. AB - The authors found, that the incidence of hypochromic, microcytic anaemia was 4 percent, and more than half of the children were suffered from iron deficiency. The causes are the inadequate daily iron uptake and/or increase iron requirement. It is very important to increase the iron content of the food and/or the prophylactic or therapeutic iron treatment. PMID- 2247308 TI - [Urinary tract infections caused by Staphylococcus saprophiticus in children]. AB - Staphylococcus saprophyticus was cultured from the urine of a pyelonephritic newborn as well as a 13 years old boy with symptoms of low urinary tract infection. Cefotaxime respectively Penicillin treatment resulted cure in both cases. Staphylococcus saprophyticus may be an important infective agent in children's urinary infections as well. PMID- 2247309 TI - [Removal of kidney calculi in children by extracorporeal shock wave therapy]. AB - ESWL treatment for renal calculi was used in 19 occasion in 16 children aged 6-15 years. 13 children were stone free 3 months after the treatment. All of the stones were located in the renal calices or in the renal pelvis. The possibilities of the procedure, as well as its effects were examined with the use of urography, ultrasound, isotop studies and magnetic resonance imaging. PMID- 2247310 TI - [Comment on the availability of medical documentation]. PMID- 2247311 TI - [Do we need a publication reform?]. PMID- 2247312 TI - [Hospital experience of Romanian medical students in Hungary]. PMID- 2247313 TI - Study of verbal description in neuropathic pain. AB - The aim of this paper is to study the quality of verbal description and its diagnostic value in neuropathic pain. The verbal description of pain as assessed by a French adjective list questionnaire (QDSA) is compared between a group of 100 patients with neuropathic pain and a mixed group of 97 chronic benign and cancer non-neuropathic pain patients. Seventeen descriptors of the 61 QDSA descriptors have a significant intergroup frequency difference. By principal component analysis and Varimax rotation of the intercorrelation matrix of descriptors in the neuropathic group. 7 factors accounting for 66.0% of the total variance are derived. Six factors reflect purely sensory or affective aspects of the pain experience. Seven descriptors from the discriminant analysis function correctly assign 77% of neuropathic pain patients and 81% of the non-neuropathic pain patients. In a second neuropathic pain group of 32 patients, the discriminant function coefficient permits correct diagnostic categorization in 66% of the cases. Implications for clinical practice and trials are discussed. PMID- 2247314 TI - Psychosocial correlates of temporomandibular joint pain and dysfunction. AB - This study examines psychological differences between temporomandibular joint pain and dysfunction (TMJPD) patients, pain controls, and healthy controls. Two hundred and two patients were classified, according to the diagnostic criteria of Eversole and Machado, as either myogenic facial pain (n = 42), internal derangement type I (n = 69), internal derangement type II (n = 85), or internal derangement type III (n = 6). Patients completed the Basic Personality Inventory, the Illness Behavior Questionnaire, the Multidimensional Health Locus of Control, the Perceived Stress Scale, and the Ways of Coping Checklist. Subjects also answered question pertaining to TMJPD symptomatology, including chronicity and severity. After conservative treatment with simple jaw exercise and ultrasound, patients were contacted again at 5 months to complete follow-up questionnaires similar to those previously completed. Comparison groups were comprised of 79 patients attending outpatient physiotherapy clinics for pain-related injuries not involving the temporomandibular joint and 71 pain-free, healthy students. Data were analyzed using multivariate statistics. The results indicate a significant relationship between pain intensity (and to some extent chronicity) and diverse measures of personality among the pain controls but not among the TMJPD patients. This calls into question the validity of assuming individual pain disorders are subsets of a larger, homogenous pain disorder population. TMJPD patients and pain controls score higher on hypochondriasis and anxiety than the pain-free controls but these elevations are not clinically significant. The elevations decrease to normal levels in response to a positive treatment outcome. There were no differences between the TMJPD patients and the pain controls on any of the measures. These results suggests that TMJPD patients do not appear to be significantly different from other pain patients or healthy controls in personality type, response to illness, attitudes towards health care, or ways of coping with stress. PMID- 2247315 TI - Quantification of biomedical findings of chronic pain patients: development of an index of pathology. AB - Difficulties in assessing and quantifying the biomedical signs and symptoms that may be related to patients' reports of pain are well recognized. Although there appears to be some consensus among physicians as to the potential utility of examination and diagnostic tests frequently used to evaluate chronic pain patients, little attention has been paid to the reliability of interpreting the results of these procedures. Moreover, the integration of biomedical findings to form a general index of pathology associated with chronic pain has been a difficult problem to solve because not all biomedical procedures used to evaluate pain patients are necessarily relevant or indicated for a specific patient. Two studies are presented that were designed to evaluate the reliability of 23 biomedical procedures commonly used to evaluate chronic pain patients and to determine if findings on these procedures can effectively be combined to form a reliable index of physical pathology. The results of study 1 suggest that 17 of the 23 procedures can be applied in clinical setting with acceptable levels of reliability. Study 2 provides evidence that an innovative weighted scoring approach, based on current medical consensus, can be used to produce a reliable, general index of pathology that is independent of the number of procedures used to evaluate patients. The utility of this quantification approach to biomedical findings for clinical and research purposes is discussed. PMID- 2247316 TI - Is emotional disturbance a precipitator or a consequence of chronic pain? AB - The present study examined the relationship between psychological factors and pain in order to assess the contribution of emotional disturbance to the perpetuation of pain. A group of 163 chronic pain suffers in multiple settings was compared with 81 control subjects on measures of personal history antecedent to pain onset, as well as on measures of current emotional disturbance. In addition, these psychological variables were examined for their associations with subjectively rated pain intensity. Overall, pain was found to be related to more current depression and less current life satisfaction, but was not associated with most of the personal history variables examined. These results suggests that emotional disturbance in pain patients is more likely to be a consequence than a cause of chronic pain. The dangers of routinely ascribing intractable pain to psychological causation are discussed in the light of these findings. PMID- 2247317 TI - Temporary increase in leg pain resulting from lumbar sympathetic blockade. PMID- 2247318 TI - Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. AB - The lumbar and cervical spinal dorsal horns of adult rats with a chronic (8 days) constriction injury of the sciatic nerve on one side (and a sham operation on the other) were examined for signs of transsynaptic degeneration. The incidence of neurons with signs of degeneration (pyknosis and hyperchromatosis; 'dark neurons') was significantly increased in the lumbar dorsal horn on both sides. The ipsilateral lumbar increase was significantly greater than the contralateral increase. There was no increase in the incidence of dark neurons in the cervical dorsal horns of the same rats. The distribution of lumbar dark neurons was similar bilaterally. The majority of the dark neurons were found in the sciatic nerve's territory in laminae I-II. A second group of rats received the same surgery but in addition received a series of 7 daily subconvulsive doses of strychnine. Dark neurons were again found bilaterally (with ipsilateral predominance) in the sciatic nerve's territory in lumbar laminae I-II, but the incidence was significantly greater than that found in the group that did not receive strychnine. The same result was obtained in a third group of strychnine treated rats when the sham operation was omitted. Thus the appearance of contralateral dark neurons is not dependent on unintentional nerve damage created by the sham procedure. An additional group of rats was sacrificed 8 days after receiving a unilateral sciatic nerve transection, a contralateral sham operation, and the 7 daily strychnine injections. There was no increase in the incidence of dark neurons in any of these rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247319 TI - Intrathecal etorphine, fentanyl and buprenorphine on spinal nociceptive neurones in the rat. AB - Single unit recordings were made in the lumbar dorsal horn in the intact anaesthetized rat from convergent, multireceptive neurones. Activity was evoked by A beta and C fibre transcutaneous electrical stimulation of hind paw receptive fields. Three opioids, fentanyl, etorphine and buprenorphine were applied either intrathecally or intravenously and their effects on neuronal responses were examined. Intrathecal fentanyl and etorphine produced clear selective naloxone reversible inhibitions of C fibre-evoked responses (ED50 = 24 micrograms and 0.6 micrograms respectively). Fentanyl, a mu opioid receptor agonist, was more potent at a given dose when given systemically, but etorphine, a non-selective opioid agonist, was similarly potent by both routes. In contrast to fentanyl and etorphine, intrathecal buprenorphine produced facilitations of C fibre-evoked responses at a low dose (15 micrograms), but inhibited both C and A beta fibre evoked responses equally at a higher dose (125 micrograms). Inhibitions were found to be irreversible by naloxone. No inhibition of either C or A beta responses occurred following intravenous buprenorphine (10-1070 micrograms). The results are discussed in the light of the relationships between lipophilicity, opioid receptor selectivity and potency for spinally applied opioids. PMID- 2247320 TI - The formalin test in mice: effect of formalin concentration. AB - The effect of different formalin concentrations on the nociceptive response in the formalin test was examined in mice. Subcutaneous formalin injection induces 2 distinct periods of high licking activity: an early phase lasting the first 5 min, and a late phase lasting 20-30 min after the injection. Formalin concentrations of 0.02-0.2% induced only the early phase, while concentrations of 1% or more induced both the early phase and the late phase. The ability of the test to show the antinociceptive effect of morphine and acetylsalicylic acid was similar for high and low formalin concentrations. For both these analgesics, a lower dose was needed to induce antinociception in the late phase than in the early phase using the same formalin concentration. Indomethacin had no effect in the early phase. In the late phase indomethacin induced antinociception when 1% formalin was used, while no significant effect was observed using 5% formalin. Clear histological changes in the paw were demonstrated after formalin concentrations that induced both phases. Lower formalin concentrations induced only very small changes. Using a low formalin concentration (0.2%), repeated testing using the same paw could be performed at intervals of 1 week without any significant change in the response. It was concluded that the formalin concentration should be kept as low as possible to minimize the suffering of the animal. Formalin concentrations of 0.05-0.2% are recommended for studying the early phase. Formalin concentrations of 1% or higher have to be used when studying the nociceptive response in the late phase. PMID- 2247321 TI - Quantitative evaluation of hypnotically suggested hyperaesthesia and analgesia by painful laser stimulation. AB - The ability to reduce both clinically and experimentally induced pain by hypnotic suggestion of analgesia is well known. However, the nature of hypnotic analgesia still remains uncertain. Attempts to demonstrate and identify specific psychophysiological mechanisms have, so far, been unsatisfactory. Methodological problems in inducing pain and monitoring physiological responses may be the reason for this lack of success. In the present study, we have attempted to eliminate some of these methodological problems. The sensory and pain thresholds to laser stimulation were determined, and the laser-evoked brain potentials were measured for 8 highly hypnotically susceptible subjects in 3 conditions: (1) waking state, (2) suggestion of hyperaesthesia, (3) suggestion of analgesia. The thresholds were reduced during induced hyperaesthesia and increased during analgesia. During hyperaesthesia sensations could be evoked by laser intensities which were below intensities that could be perceived in the awake state. The amplitude of the evoked brain potentials increased during hyperaesthesia and decreased during analgesia. The latency of the potential remained constant. The perception of pain during hypnosis can change very fast, indicating that slow endogenous mechanisms may play only a minor role in suggested hyperaesthesia/analgesia. PMID- 2247322 TI - Non-anatomical symptoms and signs: a response to critics. PMID- 2247323 TI - Does stimulus context affect loudness or only loudness judgments? AB - Marks (1988) reported that when equal-loudness matches were inferred from magnitude estimates of loudness for tones of two different frequencies, the matches were affected by changes in the stimulus intensity range at both frequencies. Marks interpreted these results as reflecting the operation of response biases in the subjects' estimates; that is, the effect of range was to alter subjects' judgments but not necessarily the perception of loudness itself. We investigated this effect by having subjects choose which of two tone pairs defined the larger loudness interval. By using tones of two frequencies, and varying their respective intensity ranges, we reproduced Marks' result in a procedure devoid of numerical responses. When the tones at one frequency are all soft, but the tones at the other frequency are not all soft, cross-frequency loudness matches are different from those obtained with other intensity range combinations. This suggests that stimulus range affects the perception of loudness in addition to whatever effects it may have on numerical judgments of loudness. PMID- 2247324 TI - The perception of 3-dimensional affine structure from minimal apparent motion sequences. AB - The research described in the present article was designed to identify the minimal conditions for the visual perception of 3-dimensional structure from motion by comparing the theoretical limitations of ideal observers with the perceptual performance of actual human subjects on a variety of psychophysical tasks. The research began with a mathematical analysis, which showed that 2-frame apparent motion sequences are theoretically sufficient to distinguish between rigid and nonrigid motion and to identify structural properties of an object that remain invariant under affine transformations, but that 3 or more distinct frames are theoretically necessary to adequately specify properties of euclidean structure such as the relative 3-dimensional lengths or angles between nonparallel line segments. A series of four experiments was then performed to verify the psychological validity of this analysis. The results demonstrated that the determination of structure from motion in actual human observers may be restricted to the use of first order temporal relations, which are available within 2-frame apparent motion sequences. That is to say, the accuracy of observers' judgments did not improve in any of these experiments as the number of distinct frames in an apparent motion sequence was increased from 2 to 8, and performance on tasks involving affine structure was of an order of magnitude greater than performance on similar tasks involving euclidean structure. PMID- 2247325 TI - The influence of spatial contrast on the frequency-dependent nature of vibration sensitivity. AB - Several stimulus configurations have been described for measuring the threshold for vibration perception. One such configuration, used primarily for screening for peripheral nervous system function, for example, consists of a matrix of 24 rows and 6 columns of tiny pins vibrating at 230 Hz, with the even rows of pins vibrating in opposite phase to the uneven rows. In order to determine which class of mechanoreceptors is being tested with such a stimulus, the frequency dependence of the threshold for vibration perception was measured with a similar stimulus configuration in a group of younger subjects and in a group of older subjects. Moreover, the stimulus configuration could be changed from opposite phase stimulation to equal phase stimulation, wherein all pins vibrated with equal phase. In the range above 160 Hz, it appeared that in younger subjects the threshold of the Pacinian receptor system was evaluated with both modes of stimulation, although the sensitivity for opposite phase stimulation was reduced relative to the sensitivity for equal phase stimulation. In the older subjects, equal phase stimulation also appeared to evaluate the Pacinian receptor system. However, with the opposite phase stimulation, the non-Pacinian receptors tended to be evaluated. Below 100 Hz, sensitivity was greater for opposite phase than for equal phase stimulation in both groups. Moreover, with both modes of stimulation, a sensitivity maximum at 40 Hz could be obtained, which was tentatively ascribed to the rapidly adapting class of mechanoreceptors. PMID- 2247326 TI - The effect of vibrato on the recognition of masked vowels. AB - Five experiments on the identifiability of synthetic vowels masked by wideband sounds are reported. In each experiment, identification thresholds (signal/masker ratios, in decibels) were measured for two versions of four vowels: a vibrated version, in which FO varied sinusoidally around 100 Hz; and a steady version, in which F0 was fixed at 100 Hz. The first three experiments were performed on naive subjects. Experiment 1 showed that for maskers consisting of bursts of pink noise, vibrato had no effect on thresholds. In Experiment 2, where the maskers were periodic pulse trains with an F0 randomly varied between 120 and 140 Hz from trial to trial, vibrato slightly improved thresholds when the sound pressure level of the maskers was 40 dB, but had no effect for 65-dB maskers. In Experiment 3, vibrated rather than steady pulse trains were used as maskers; when these maskers were at 40 dB, the vibrated versions of the vowels were slightly less identifiable than their steady versions; but, as in Experiment 2, vibrato had no effect when the maskers were at 65 dB. Experiment 4 showed that the unmasking effect of vibrato found in Experiment 2 disappeared in subjects trained in the identification task. Finally, Experiment 5 indicated that in trained listeners, vibrato had no influence on identification performance even when the maskers and the vowels had synchronous onsets and offsets. We conclude that vibrating a vowel masked by a wideband sound can affect its identification threshold, but only for tonal maskers and in untrained listeners. This effect of vibrato should probably be considered as a Gestalt phenomenon originating from central auditory mechanisms. PMID- 2247327 TI - Effects of alcohol and extended practice on divided-attention performance. AB - The effects of alcohol and extended practice on divided attention were investigated using a visual tracking task and an auditory detection task. Subjects performed the tasks with and without alcohol, under single-task (S) and dual-task (D) conditions, both before and after they had received extended practice under single-task conditions without alcohol. Tracking accuracy improved with practice and was impaired under divided-attention conditions but was not affected by alcohol. Speed of detection was impaired by alcohol, improved by practice, and impaired by divided attention. Extended practice did not reduce the influence of alcohol. The effects of both alcohol and practice on speed of detection were significantly greater under dual-task conditions than under single task conditions. Analysis of detection-task reaction times in terms of relative divided-attention costs, (D-S)/S, showed no effect of alcohol, but a highly significant reduction in costs with extended practice. It is concluded that (1) alcohol and practice can have quantitatively, but not qualitatively, similar effects on speeded performance, and (2) the effect of alcohol is not influenced by the attentional requirements of the task. PMID- 2247328 TI - The influence of saccade length on the saccadic suppression of displacement detection. AB - The decrease in sensitivity to spatial displacement which accompanies a voluntary horizontal saccadic eye movement was measured as a function of the length of the saccade. Threshold for detecting the displacement increased linearly from about 0.3 degrees to 1.2 degrees as saccade length increased from 4 degrees to 12 degrees. The variability (standard deviation) of the discrimination increased linearly with saccade length as well, and hence also linearly with the displacement threshold. These results, along with our previous finding that the increase is not a consequence of the saccadically generated spatiotemporal smearing of the retinal image (Li & Matin, 1990), support the proposal that displacement detection is based on a constant internal signal/noise ratio whose denominator is a measure of the variability of the extraretinal signal regarding eye position, and that the reduction in sensitivity is a result of a transient increase of this variability in the temporal neighborhood of a saccade. PMID- 2247329 TI - Perspective taking, pictures, and the blind. AB - Congenitally blind, late blind, and blindfolded sighted controls attempted a Piagetian perspective-taking (three-mountain) task. Piaget used the term perspective to mean point of view (Piaget & Inhelder, 1967, p. 210), and the present usage does not imply linear perspective. Subjects used raised-line drawings to depict alternative points of view of an array of three geometric solid forms (cube, cone, and ball). They then identified the point of view of raised-line drawings. The effect of visual status on accuracy was nonsignificant for both response measures. Using alternating vision of the array and drawings, sighted subjects in a control condition performed like the congenitally blind. However, congenitally blind individuals did require more time than the other subjects for the perspective-taking task. In an additional experiment, no difference was found between the three groups in the accuracy or speed of tactile shape matching. The results suggest that visual imagery and visual experience are not necessary for tactile perspective taking. PMID- 2247330 TI - Illusion decrement and transfer of illusion decrement in obtuse- and acute-angle variants of the Poggendorff illusion. AB - Illusion-decrement and transfer-of-illusion-decrement procedures were used to examine the contribution of the obtuse- and acute-angle components of the Poggendorff pattern to the standard Poggendorff illusion. In the first four experiments, subjects were required to scan between the oblique lines of the Poggendorff pattern during the inspection phase of the decrement procedure. However, because of a possible confound associated with this procedure, a different decrement technique was used in Experiment 5. The results of Experiment 5 confirm and extend MacKay and Newbigging's (1977) finding that similar amounts of transfer to the standard pattern are obtained from the obtuse- and acute-angle patterns as from the standard pattern itself: In showing that the acute- and obtuse-angle components both contribute to the illusion, these findings question the plausibility of those theories of the Poggendorff illusion which do not assign any significant role to the acute-angle component. Furthermore, the potential confound associated with the decrement procedure of Experiments 1-4 suggests that the results of other studies obtained with similar procedures need to be reevaluated. PMID- 2247331 TI - Can shape be perceived by dynamic touch? AB - The possibility that some aspects of the shapes of solid objects can be perceived through dynamic touch, even when the objects are not touched, but simply wielded with a handle, was investigated in four experiments. Wooden solids were constructed of three sizes and five shapes: hemisphere, cylinder, parallelepiped, cone, and pyramid. Experiments 1 and 2 involved comparisons (judgments of same or different) between and among wielded objects of the same mass. In Experiments 3 and 4, subjects were required to wield an object and to select a match from a visible arrangement of objects of the five shapes; the wielded objects were of two sizes, each different from that of the visible objects. The success of subjects at these tasks, and the patternings of errors, are seen to involve the characteristic moment of inertia profiles of each shape, and a ratio of the object's resistances to rotation around orthogonal axes is shown to be a strong predictor of performance in the identification experiments. The results are discussed with reference to dynamic touch and to the notion of shape invariants that do not reduce to aspects of object surface. PMID- 2247332 TI - Visual space-time interactions: effects of adapting to spatial frequencies on temporal sensitivity. AB - To study how adaptation to spatial frequency patterns affects temporal sensitivity in vision, observers were selectively adapted for 4 min to either a high- or a low-spatial-frequency sinusoidal grating (12 and 2 cpd, respectively). Their sensitivities to modulation of a blurred patch at high or low temporal frequencies (12 Hz and 2 Hz, respectively) were measured, before and after the adaptation period, by using the yes/no task of signal detection theory. The data consistently indicated that spatial adaptation differentially affected the observers' sensitivities to temporal signals. Specifically, when the observers were adapted to low spatial frequencies, their sensitivity to low temporal frequencies was reduced; when they were adapted to high spatial frequencies, their sensitivity to high temporal frequencies was increased. These results have implications for the psychophysical measurements of temporal and spatial sensitivity, as well as for the issue of the separability of spatial and temporal properties of individual channels. PMID- 2247333 TI - Determinants of subjective contour: Bourdon illusions and "unbending" effects. AB - Wenderoth and O'Connor (1987b) reported that, although matches to the straight edge of two triangles placed apex to apex revealed an apparent bending in the direction of the chevron formed by the hypotenuse pair (the Bourdon effect), no perceptual unbending of the bent chevron occurred. Using subjective contour figures, Walker and Shank (1988b) found large and approximately equal bending and unbending effects, consistent with two theories that they proposed. In Experiment 1, using adjustable chevron matching and subjective contours, we found that Bourdon effects, equivalent in magnitude to those reported by Walker and Shank, were 4-5 times larger than unbending effects. In Experiment 2, we used a variation of Walker and Shank's measurement technique, in which subjects selected a matching angle from a graded series. We obtained Bourdon effects similar to those in Experiment 1, but much larger unbending effects. Nevertheless, Bourdon effects were significantly larger than unbending effects in one set of data; and in another, Bourdon test means were larger than unbending test means. In both data sets, there was a large and significant pretest bending effect, which enhanced the magnitude of unbending test minus pretest scores. These results were consistent with our theory but not the theories of Walker and Shank. The variance of unbending test matches, 3-4 times that of Bourdon test matches, reflected the task difficulty. We propose that subjective obtuse angle contraction that exceeds real obtuse angle contraction explains the fact that unbending effects are larger in subjective than in real contours. PMID- 2247334 TI - The extraretinal signal from the pursuit-eye-movement system: its role in the perceptual and the egocentric localization systems. AB - The accuracy of perceptual judgment of the distance of a moving target tracked at various velocities by pursuit eye movements was examined in relation to the amount of two types of eye movement (smooth pursuit eye movement and compensatory saccade) involved in eye tracking. The perceptually judged distance became shorter as the amount of pursuit-eye-movement component in eye tracking increased. A detailed analysis of the eye-movement data and the size of perceptual underestimation indicated that the underestimation was mainly caused by inaccurate extraretinal information derived from the pursuit-eye-movement system, which underestimated the distance at a constant ratio, irrespective of the velocity of tracking. Egocentric localization was not affected by the mode of eye movements, indicating that the egocentric localization system functions without interference from the inaccurate information from the pursuit-eye movement system. PMID- 2247336 TI - Secretagogue effects on intracellular calcium in pancreatic duct cells. AB - Regulation of intracellular free calcium ([Ca2+]i) in single epithelial duct cells of isolated rat and guinea pig pancreatic interlobular ducts by secretin, carbachol and cholecystokinin was studied by microspectrofluorometry using the Ca2(+)-sensitive, fluorescent probe Fura-2. Rat and guinea pig duct cells exhibited mean resting [Ca2+]i of 84 nM and 61 nM, respectively, which increased by 50%-100% in response to carbachol stimulation, thus demonstrating the presence of physiologically responsive cholinergic receptors in pancreatic ducts of both species. The carbachol-induced increase in [Ca2+]i involved both mobilization of Ca2+ from intracellular stores and stimulation of influx of extracellular Ca2+. In contrast, neither cholecystokinin nor secretin showed reproducible or sizeable increases in [Ca2+]i. Both rat and guinea pig duct cells showed considerable resting Ca2+ permeability. Lowering or raising the extracellular [Ca2+]i led, respectively, to a decrease or increase in the resting [Ca2+]i. Application of Mn2+ resulted in a quenching of the fluorescence signal indicating its entry into the cell. The resting Ca2+ and Mn2+ permeability could be blocked by La3+ suggesting that it is mediated by a Ca2+ channel. PMID- 2247335 TI - Functional asymmetry in phosphate transport and its regulation in opossum kidney cells: parathyroid hormone inhibition. AB - The sidedness (apical vs basolateral) of the inhibitory of phosphate (Pi) transport by parathyroid hormone (PTH) was investigated in opossum kidney (OK) cell monolayers grown on permeant support. PTH was found to regulate the activity of only the apical Na Pi cotransporter, having no effect on the basolateral transport systems. Transport inhibition was approximately 100-fold more sensitive to apical PTH application (Kd: 5 x 10(-12) M) than to basolateral application (Kd: 5 x 10(-10) M). The time-course of the inhibitory response was identical from the two cell surfaces, with half-maximum inhibition occurring at about 20 min and almost full inhibition by 90 min. Experiments on diffusion and degradation demonstrated that the difference in Kd at the two cell surfaces was not due to differential metabolism or diffusion. Tests of cooperativity between the apical and basolateral regulatory events at intermediate concentrations suggested that the presence of PTH on one side of the monolayer reduced the scope of response from the other side. At maximum doses of PTH (10(-7)-10(-8) M) the transport inhibition from either side was equal and not additive. We conclude that in OK-cell monolayers grown on permeant support only apical Na/Pi co transport is sensitive to PTH inhibition and that PTH receptor properties may be different on the apical and basolateral surfaces. PMID- 2247337 TI - Inactivation of brown adipose tissue thermogenesis by oestradiol treatment in cold-acclimated rats. AB - Both cold-acclimated female rats and rats at thermoneutrality received 0.15-0.20 mg daily of 17 beta-oestradiol over 15 days via a Silastic capsule implanted subcutaneously. Controls received empty implants. Comparison between the oestradiol-treated animals and the untreated controls revealed that at thermoneutrality, oestradiol treatment decreased food intake and body weight gain, but did not affect brown adipose tissue (BAT) thermogenesis and composition. By contrast, in cold-acclimated rats, oestradiol treatment did not modify food intake or body weight gain, but it decreased BAT thermogenesis. It is concluded that the effects of oestradiol treatment on BAT depend on the activity of the tissue, i.e. it has no effect on BAT when the tissue is thermogenically inactive, but it decreases cold-induced BAT thermogenesis. It is suggested that oestradiol could be the hormonal factor responsible for the previously observed inactivation of BAT thermogenesis during pregnancy in cold-acclimated rats. PMID- 2247338 TI - Cold-induced thermogenesis in hypothyroid rats. AB - Hypothyroidism was induced in adult rats by oral administration of methimazole. Euthyroid and hypothyroid rats were maintained at 23 degrees C or exposed at 6 degrees C for 3 weeks. Both euthyroid and hypothyroid rats maintained at 23 degrees C had similar interscapular brown adipose tissue (BAT) composition and thermogenic activity. Cold-exposed hypothyroid rats showed the same interscapular BAT mass and gross tissue composition as cold-exposed euthyroid animals, but the interscapular BAT of cold-exposed hypothyroid rats did not show the characteristic increase in GDP binding, and the increase in mitochondrial mass was lower than in euthyroid rats. From these results we conclude that thyroid hormones do not influence BAT significantly when thermogenic requirements are moderate, but they participate in the trophic response of the tissue when thermogenic requirements are intense. This thyroid hormone participation in the BAT trophic response occurs at the mitochondrial level, both in quantitative (mitochondrial mass) and qualitative (GDP-binding) aspects. PMID- 2247339 TI - Effects of the administration of angiotensin II on cardiac glycogen metabolism in the rat. AB - Changes in glycogen metabolism after an intravenous injection of angiotensin II were investigated in the left and right ventricles of the rat heart, as a function of location within the ventricular wall. Hearts were cut into 100 microns thin section, all of which were analysed for glycogen content, glucose incorporation into glycogen and 2-deoxyglucose uptake and phosphorylation after the intravenous injection of 14C-labelled sugar. In control hearts, glycogen levels were uniform across the wall in both ventricles, while the rate of sugar uptake and phosphorylation, and that of glucose incorporation into glycogen, were significantly higher in the subendocardial myocardium of the left ventricular wall. After angiotensin II administration, heart glycogen levels decreased slightly in the left, but not in the right ventricle, while 2-deoxyglucose uptake and phosphorylation, and glucose incorporation into glycogen, increased 2,5- and 5-fold, respectively. With regard to the distribution across the wall of the left ventricle after angiotensin administration, glycogen levels and glucose incorporation into glycogen were uniformly distributed, whereas sugar phosphorylation was still higher in the subendocardium. PMID- 2247340 TI - Diffraction ellipsometry studies of osmotically compressed muscle fibers. AB - Microstructural features of relaxed, skinned muscle fibers compressed with polyvinylpyrrolidone were examined by optical diffraction ellipsometry. This technique is sensitive to the optical anisotropy within the muscle, including that due to intrinsic properties of the protein molecules as well as that due to the regular arrangement of proteins in the surrounding medium. The change in polarization state of light after interacting with the muscle is described by the differential field ratio (DFR) and birefringence (delta n). Compression of single fibers (sarcomere length = 2.6 microns) with 0%-21% polyvinylpyrrolidone caused an increase of up to 23% and 31% for DFR and delta n, respectively. The largest increase in both parameters occurred at intermediate sarcomere lengths. Theoretical modelling of the results suggest that the average S-1 tilt angle may be reduced upon compression of the filament lattice. This is supported by experiments in which S-1 was enzymatically cleaved with alpha-chymotrypsin. Separate experiments comparing fibers with intact membranes and skinned fibers compressed to an equivalent lattice spacing showed little difference in DFR or delta n. PMID- 2247341 TI - Favourable associations between the myosin heavy-chain and light-chain isoforms in human skeletal muscle. AB - Histochemical and biochemical analyses were performed in order to examine the relationship between myosin light-chain (LC) isoforms and fibre-type distributions in whole human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis muscle in six healthy men, and analysed for the relative area occupied by each fibre type (percentage of fibre type area) and the molar ratio of each LC isoform. The percentage of type I fibre area was positively correlated with the molar ratio of slow LC (LC1s and LC2s) to total LC. The regression line was located below the line of unity. Also, the ratio of percentage of type IIa fibre area to that of type II fibre area was positively correlated with the molar ratio of the fast alkali LC LC1f to fast alkali LCs LC1f and LC3f. These results support previous study, having shown that in human skeletal muscle some type I fibres express various amounts of fast LC in addition to slow LC and suggest that fast myosin heavy-chain HCIIa is favourably associated with LC1f, whereas HCIIb is favourably associated with LC3f. PMID- 2247342 TI - Impaired hydroosmotic response to vasopressin of cortical collecting tubules from lithium-treated rabbits. AB - The hydroosmotic action of [arginine]vasopressin (vasopressin, 25 microU/ml) and of 8-Br-cAMP (10(-4)M) was studied in vitro in perfused cortical collecting tubules (CCT) isolated from rabbits fed with lithium chloride for 3 weeks. Vasopressin-dependent water reabsorption was significantly inhibited by 65% although no lithium was used in the in vitro experiments. The hydroosmotic action of 8-Br-cAMP was also inhibited by previous Li treatment, but the effect was smaller in magnitude. Water intake, diuresis, and urinary osmolality were no different in the lithium-treated animals as compared with respective pretreatment values or with control animals given an equivalent amount of sodium chloride. Neither the creatinine clearance nor the maximal urinary concentrating ability were modified by lithium treatment. A mathematical model simulating water reabsorption along the CCT predicts that a 65% reduction of vasopressin stimulated hydraulic conductivity, as observed in the Li group, may not be sufficient to prevent a complete osmotic equilibration at the end of the CCT in vivo. We conclude that: (a) in the rabbit, lithium administration induces an impairment of the hydroosmotic action of vasopressin in the CCT, which is due to an inhibition of pre- and post-cAMP events. (b) The inhibition of vasopressin action can be demonstrated in vitro at a time when no detectable impairment of the water conservation process occurs in vivo. PMID- 2247343 TI - Biphasic rises in cytosolic free Ca2+ in association with activation of K+ and Cl conductance during the regulatory volume decrease in cultured human epithelial cells. AB - During exposure to a hypotonic solution (55% osmolarity), cultured human epithelial (Intestine 407) cells exhibit a regulatory volume decrease after osmotic swelling. This process is known to involve parallel activation of volume regulatory K+ and Cl- conductances. Biphasic increase in the cytosolic free Ca2+ concentration ([Ca2+]i) were observed by microspectrofluorometry, in fura-2 loaded cells upon hypotonic stress. Electrophysiological studies with Ca2(+) selective and conventional microelectrodes indicated that a biphasic [Ca2+]i increase was associated with a biphasic hyperpolarization, whereas an interposing [Ca2+]i decrease coincided with a transient depolarization. A Ca2+ ionophore, ionomycin, produced a sustained Ca2+ increase and a prolonged hyperpolarization which was sensitive to the K+ channel blocker, quinine. A subsequent hypotonic challenge gave rise to a depolarization, which was sensitive to a stilbene derivative Cl- channel blocker, without inducing further changes in [Ca2+]i. Normal cell volume regulation in a hypo-osmotic medium could take place even in the presence of ionomycin. It is concluded that a biphasic [Ca2+]i increase is closely associated with activation of the volume-regulatory K+ conductance, and that the interposing [Ca2+]i decrease is neither a causative factor for activation of the volume-regulatory Cl- conductance nor a prerequisite for regulatory volume decrease in epithelial cells exposed to a hypotonic solution. PMID- 2247344 TI - Intracellular free calcium concentration/force relationship in rabbit inferior vena cava activated by norepinephrine and high K+. AB - The changes in isometric force and the underlying fluctuations in intracellular free calcium concentration ([Ca2+]i) were monitored simultaneously in thin sheets of rabbit inferior vena cava loaded with the fluorescent Ca2+ indicator fura-2. In resting tissues bathed in physiological saline solution, the estimated [Ca2+]i was approximately 105 nM. The alpha-adrenergic agonist norepinephrine (10 microM) caused an initial rise in [Ca2+]i to 264 nM during force development, which dropped to 216 nM during force maintenance. The maintained norepinephrine-induced increase in force and [Ca2+]i was reversed in Ca2(+)-free (2 mM EGTA) solution. Membrane depolarization by high K+ (80 mM) significantly increased [Ca2+]i to 234 nM. Compared to norepinephrine, high K+ caused about the same steady-state increase in [Ca2+]i, but a smaller increase in force. [Ca2+]i/force curves were constructed at different concentrations of extracellular Ca2+, with either norepinephrine or high K+ as a stimulant. The curve generated with norepinephrine was located to the left of that generated with high K+. PMID- 2247345 TI - Regulation of force in skinned, single cells of ferret aortic smooth muscle. AB - An isolation technique was developed for single cells from the ferret aorta, which resulted in the isolation of long (87 +/- 27 microns; x +/- SD, n = 62), relaxed, pharmacologically active smooth muscle cells. These cells were attached to microtools, one of which was connected to a force transducer. Force in maximally phenylephrine-stimulated contractions of the intact cells averaged 2.3 +/- 1.4 microN (n = 17). After cell skinning with saponin, the threshold for force development was 0.05 microM [Ca2+], and force reached a maximum of 4.4 +/- 1.6 microN (n = 36) at 0.5 microM [Ca2+]. Plots of relative steady-state force vs pCa (-log10[Ca2+]) were fit to the Hill equation, which yielded a pCa at half maximal force of 6.87 +/- 0.30 and a Hill coefficient of 2.3 +/- 1.4 (n = 29). When 2.5 microM calmodulin was added to the solutions, the calcium sensitivity of force was significantly increased (P less than 0.05) without changing the maximal force (P greater than 0.05). In a solution of pCa 7, the skinned cells developed 2.5 +/- 0.5 microN (n = 5) of force when stimulated with a phorbol ester. The addition of a specific inhibitor (17 kDa) of protein kinase C to the calcium buffers depressed (P less than 0.05) the maximally Ca2(+)-activated force without a change in the calcium sensitivity of force (P greater than 0.05). These data strongly suggest that in vascular smooth muscle, protein kinase C may be involved in a physiological, regulatory system for force. PMID- 2247346 TI - Na(+)-activated K+ current in cardiac cells: rectification, open probability, block and role in digitalis toxicity. AB - The Na(+)-activated K+ current was studied in inside-out patches and in whole cells isolated from the guinea-pig cardiac ventricle. The single channel conductance showed inward rectification for K+i less than K+e, but outward rectification for K+i greater than K+e. The open probability was dependent on Na+i and Na+,K(+)-pump activity. In the presence of pump blockade the channel remained active at low Na+i. Similar results were obtained in whole cells. These results suggest the existence of Na+ gradients depending on Na+,K(+)-pump activity and passive inward leak of Na+. The channel and whole cell current were blocked by R56865. The drug did not change the single channel conductance but markedly reduced open probability by shortening burst duration. The current may play an important role in action potential shortening during pump blockade. PMID- 2247347 TI - [Multifocal fatty infiltration of the liver: report of six cases]. AB - Images of computed tomography (CT), ultrasonography (US), angiography and radionuclide imaging were analyzed in six cases of multifocal fatty infiltration of the liver. Histologic confirmation of fatty infiltration was obtained in one patient by percutaneous biopsy. In the remaining patients, presumptive confirmation of the diagnosis was based on the CT number in one patient and partial or complete resolution of the lesions on repeat CT scans or US in 4 patients. CT and US were performed in all six patients. CT scans demonstrated multiple round areas of low attenuation within both lobes of the liver in all cases. US studies showed hyperechoic foci in three cases and diffuse inhomogeneous hyperechogenicity in three cases. Hepatic arteriograms in five cases and liver scintigrams in four cases showed no evidence of space-occupying lesions. In all cases, the lesions completely or partially resolved in follow-up CT and US, and in four cases the lesions disappeared within two months, so follow up examinations within about 2 months are necessary to differentiate these from liver neoplasms. PMID- 2247348 TI - [Comparison of endoscopic ultrasonography and computed tomography in detecting mediastinal and hilar lymph nodes from bronchogenic carcinoma]. AB - We investigated and compared the ability to diagnose metastasis of lung cancer to the mediastinum and hilar lymph nodes using CT and EUS (endoscopic ultrasonography by radial scanning method) in 27 patients undergoing resection of primary lung cancer and 6 autopsy cases. We also determined the relationship between the presence or absence of metastasis and the size of each lymph node based on the lymph node size measured at the time of resection and its histopathological findings, and we then set up a standard value that was the most accurate in evaluating the presence or absence of metastasis using a receiver operating characteristic (ROC) curve. When lymph node sizes appearing as images were compared with their actual sizes measured on resected specimens before formalin fixation, the short axis measured by either method was found to generally agree with the actual values, while the long axis was slightly smaller than the actual values, although EUS gave more accurate values. When the ability to diagnose metastasis was compared between CT and EUS using the standard value obtained from the ROC curve (a more than 8 mm short axis was defined as positive for metastasis), there were no differences in the ability to delineate the entire area of the mediastinum, including hilar lymph nodes. With respect to individual sites, although there was some difficulty delineating some regions in the mediastinum (pretracheal lymph node) with EUS, more lymph nodes in the mediastinum that were delineated by EUS histopathologically had metastatic lesions than those delineated by CT. However, both methods often failed to delineate hilar lymph nodes, with no difference shown between these two methods. PMID- 2247349 TI - [Asymptomatic blood pressure and pulse rate changes during intravenous urography. Ionic contrast media vs. nonionic contrast media]. AB - In 8,232 examinations of intravenous urography (4,832 examinations with ionic contrast media and 3,400 examinations with nonionic contrast media), systemic blood pressure and pulse rate were continuously monitored by an automatic blood pressure and pulse rate monitoring device before and after injection of contrast media. The intravenous injection of ionic contrast media caused mild to moderate hypotensive reactions (20%-39% decrease of systemic blood pressure) in 7 examinations (0.14%) and severe hypotensive reactions (greater than 40% decrease of systemic blood pressure) in 12 examinations (0.25%). There were no clinical symptoms other than hypotensive reactions in 8 of the 19 examinations (42.1%). On the other hand, the intravenous injection of nonionic contrast media did not cause severe hypotensive reactions but mild hypotensive reactions (20%-29% decrease of systemic blood pressure) in 3 examinations (0.09%). These 3 examinations did not have clinical symptoms other than hypotensive reactions. Of the 19 examinations using ionic contrast media, the hypotensive reactions with significant change of pulse rate (greater than 20%) was associated with increase of pulse rate in 17 examinations and decrease of pulse rate in 2 examinations. On the other hand, the hypotensive reactions had an association with a significant increase (greater than 20%) of the pulse rate in only one of the 3 examinations using nonionic contrast media. The pulse rate was unchanged after injection of contrast media in the remaining 2 examinations although there was mild hypotension. In conclusion, nonionic contrast media caused fewer and less severe changes in blood pressure and pulse rate without obvious clinical symptoms compared with ionic contrast media. PMID- 2247350 TI - [Usefulness of ioversol (MP-328) in angiocardiography--a multicenter comparative study with iopamidol]. AB - A randomized, controlled study was conducted to compare the radiographic efficacy, safety and usefulness of ioversol and iopamidol in 146 patients undergoing angiocardiography at six institutions. The hemodynamic and electrocardiographic effects were clinically insignificant and comparable for both agents. Ioversol demonstrated lower incidence of adverse reactions and less heat sensation in left coronary arteriography than those with iopamidol. Overall radiographic efficacy with ioversol was slightly better than with iopamidol, according to the evaluation by both investigators and committee members. Ioversol appears to be very useful for angiocardiography. This comparative study demonstrated the value of safety and efficacy evaluation criteria suggested by the preceding clinical trial with ioversol. PMID- 2247351 TI - A new thermoplastic resin shell for immobilization of patients receiving high dose-rate intracavitary irradiation for rectal cancer. PMID- 2247352 TI - [Fundamental studies on efficacy of intraoperative radiotherapy on pancreatic carcinomas transplanted into the pancreas of hamsters]. AB - Efficacy of intraoperative electron beam radiotherapy (IOER) on N-nitrosobis (2 hydroxypropyl) amine (BHP) induced pancreatic carcinomas transplanted into the pancreas of the Syrian golden hamsters were studied and the following results were obtained. 1. Selective electron beam application to the carcinoma transplanted into the pancreas of hamsters was accomplished using an electron beam collimator. 2. Intra-pancreatic transplantability of BHP-induced serially transplantable subcutaneous pancreatic carcinomas was 100%. 3. Intra-pancreatic transplanted pancreatic carcinomas disappeared in 2 out of 19 hamsters (11%) by 10 Gy irradiation and 7 out of 15 (47%) by 20 Gy irradiation given 2 weeks after intra-pancreatic transplantation. 4. In contrast to the linear growth of tumor size in the non-irradiated group, the tumor size showed an electron dose dependent reduction in the irradiated group. 5. Histologically, marked necrosis was noted in the irradiated group, and the intensity of necrosis differed between the 10 Gy and 20 Gy groups. 6. Direct invasion of tumor to the stomach, small intestine, large intestine, liver and abdominal wall was noted. Its incidence tended to decrease as the electron dose increased (5/19 or 26% for the control group, 4/19 or 21% for the 10 Gy group, and 1/17 or 6% for the 20 Gy group), although the difference was not statistically significant. 7. The incidences of liver and lymph node metastasis were not different between the non-irradiated and the irradiated groups. These results suggest that selective IOER on BHP-induced pancreatic carcinomas has an effectiveness to kill cancer cells in hamsters. PMID- 2247353 TI - [A digital fluoroscopic imaging system for verification during external beam radiotherapy]. AB - A digital fluoroscopic (DF) imaging system has been constructed to obtain portal images for verification during external beam radiotherapy. The imaging device consists of a fluorescent screen viewed by a highly sensitive video camera through a mirror. The video signal is digitized and processed by an image processor which is linked on-line with a host microcomputer. The image quality of the DF system was compared with that of film for portal images of the Burger phantom and the Alderson anthropomorphic phantom using 10 MV X-rays. Contrast resolution of the DF image integrated for 8.5 sec. was superior to the film resolution, while spatial resolution was slightly inferior. The DF image of the Alderson phantom processed by the adaptive histogram equalization was better in showing anatomical landmarks than the film portal image. The DF image integrated for 1 sec. which is used for movie mode can show patient movement during treatment. PMID- 2247354 TI - [Quantitative image of bone mineral content--dual energy subtraction in a single exposure]. AB - A dual energy subtraction system was constructed on an experimental basis for the quantitative image of bone mineral content. The system consists of a radiography system and an image processor. Two radiograms were taken with dual x-ray energy in a single exposure using an x-ray beam dichromized by a tin filter. In this system, a film cassette was used where a low speed film-screen system, a copper filter and a high speed film-screen system were layered on top of each other. The images were read by a microdensitometer and processed by a personal computer. The image processing included the corrections of the film characteristics and heterogeneity in the x-ray field, and the dual energy subtraction in which the effect of the high energy component of the dichromized beam on the tube side image was corrected. In order to determine the accuracy of the system, experiments using wedge phantoms made of mixtures of epoxy resin and bone mineral equivalent materials in various fractions were performed for various tube potentials and film processing conditions. The results indicated that the relative precision of the system was within +/- 4% and that the propagation of the film noise was within +/- 11 mg/cm2 for the 0.2 mm pixels. The results also indicated that the system response was independent of the tube potential and the film processing condition. The bone mineral weight in each phalanx of the freshly dissected hand of a rhesus monkey was measured by this system and compared with the ash weight. The results showed an error of +/- 10%, slightly larger than that of phantom experiments, which is probably due to the effect of fat and the variation of focus-object distance. The air kerma in free air at the object was approximately 0.5 mGy for one exposure. The results indicate that this system is applicable to clinical use and provides useful information for evaluating a time course of localized bone disease. PMID- 2247355 TI - [Modification of spontaneous lung metastasis by local radiation combined with or without immunomodifier]. AB - This study was carried out to determine the effect of local irradiation of the NFSa tumors on the incidence of lung metastases. The spontaneous lung metastases were found in those animals whose tumors had grown in size bigger than 10 mm in diameter. The incidence of metastases and the number of lung nodules were increased in those animals of irradiated group when compared to those of control group with the same size. This is probably because the irradiation of tumors resulted some retardation in their growth and thus, the irradiated tumors took a longer time to reach a given size than those unirradiated control tumors. The incidence of spontaneous lung metastases was significantly reduced by subcutaneous administration of OK-432 (2.5KE/mouse) locally into the surroundings of the tumor immediately after irradiation. The administration of OK-432 after the metastasis development was no longer effective. Both of intraperitoneal and subcutaneous administrations of OK-432 into opposite side of unirradiated thigh showed no suppression of metastasis. These results suggest that an appropriate immunostimulation combined with radiotherapy may be important for the suppression of tumor metastases. PMID- 2247356 TI - [Experimental study of the intraurethral placement of expandable metallic stents]. AB - Various types of Gianturco expandable metallic stents were implanted into the urethra of four dogs in order to evaluate the suitable expandability of the stents in urethra and also to determine the effect of the stents on the urethral wall. The stent of 1.5 cm in length and constructed of 0.010 inch round stainless steel wire with twelve zigzag bends showed the suitable expandability on the canine urethra compared to the other stents. The urethra remained patent and the inflammatory changes on the urethral wall were moderately noted. No hematuria or calcifications around the stents were noted in any dogs. The experimental data showed a potential clinical application. PMID- 2247357 TI - [Quantitative evaluation of bone mineral density of rat femur by using DEXA (dual energy x-ray absorptiometry)]. AB - BMD of rats was measured by using a collimator for small animals and HRSM-1 (high resolution scan module). There was a good correlation between obtained BMD and the known mineral content of hydroxyapatite phantoms. The presence of soft tissue and the positioning of bone did not affect BMD and BMC. There was also a good correlation between BMC and the total calcium by chemical analysis. This study confirmed high precision and accuracy of the rat femur BMD measurement. PMID- 2247358 TI - [100,000 more adults visit the dentist: a few results of November 1989]. AB - The aim of the present study was to describe the Norwegian adult population according to: 1. number of teeth present, 2. demand and utilization of dental services, 3. travel time from home to the dentist, 4. dental health behaviour, 5. fear for dental treatment. The analyses were performed on a set of national data collected in 1989, which was representative of the non-institutionalized Norwegian population 20 years and above. The sample size was 1260 individuals. About 75% of the people had 20 teeth or more present. Nine percent were edentulous. Seventy-seven percent who had demanded dental services during the last year. The average expenditure for dental treatment for those who had demanded the services during the last year was NOK 826. Fifty-three percent travelled 15 minutes or less from home to the dentist. Eighteen percent travelled 30 minutes or more. Almost everybody with their own teeth present brushed their teeth regularly once a day. Thirty-three percent of all dentate people used woodsticks regularly once a day, while 20% used toothfloss regularly. Seventy five percent had no to mild fear of the dentist, while 7% had a strong fear. Fear of the dentist was higher among women than among men. Fear of the dentist decreased by increasing age. Few people, less than 4%, had cancelled a dental appointment because of dental anxiety. There has been an improvement in dental health and dental health behaviour in Norway during the 1970's and 1980's. These improvements are discussed with special attention paid to the findings from the present study. PMID- 2247359 TI - [Salivary gland surgery to reduce salivary flow in mentally retarded]. PMID- 2247360 TI - [Treatment needs on the increase. Dental status in present and future residents of retirement homes]. PMID- 2247362 TI - [Use of freeze-dried demineralized bone in periodontal therapy]. AB - A procedure for the use of freeze-dried demineralised bone in periodontal surgery is described. Reference is made to other reconstructive procedures, and comparisons with these are made. Although there are limitations for its use, it is concluded that the method is a useful tool in the treatment for periodontitis. It approaches the ideal aim of periodontal therapy because it combines the treatment of the disease as well as induces a regeneration of the periodontium. PMID- 2247361 TI - [Hemifacial microsomia: development, diagnosis and surgical correction]. AB - Hemifacial microsomia is the second most common congenital facial anomaly. It occurs as a spontaneous event during embryogenesis and involves structures derived from the first and second branchial arch. In the past treatment of the skeletal defect was delayed until the child ceased growing and end-stage of the deformity was reached. More recent approach to analysis and treatment of this anomaly, emphasizing early treatment, to give the patient the maximum benefit of a combined surgical and orthodontic therapy, is described. PMID- 2247363 TI - [Oral health in Sudan--a challenge to Norwegian dentistry?]. AB - The paper gives an overview over the oral health situation in the Sudan. Available epidemiologic data indicate that the caries prevalence is low, but increasing. Recent information on periodontal disease is scarce. Dental fluorosis is of growing concern. Oral cancer, especially squamous cell carcinoma, is prevalent. Sudan has approximately 300 dentists to meet the treatment needs of the country's 25 million inhabitants. The great majority of the dentists live in the Khartoum area. The University of Khartoum, School of Dentistry has a capacity of 20 candidates a year. A close cooperation has been established between the dental school in Khartoum and its counterpart at the University of Bergen. PMID- 2247364 TI - [Status of orthodontics in Norway: 1990]. AB - Norwegian orthodontics has a good international reputation. Most of the treatments are performed by specialists with a thorough postgraduate training. The treatment costs are partly covered by the National Health Service and partly by the patients themselves. The amount of repayment by the Health Service is dependent on the severity of the malocclusion. Most treatments are solved by fixed appliances often in combination with extraoral growth preventing or growth stimulating appliances. Adults demanding treatment of an earlier untreated malocclusion or together with periodontal and prosthetic treatment are increasing in most practices. PMID- 2247365 TI - [Who needs orthodontic treatment?]. AB - Most people have a dentition with individual morphologic characteristics and exhibit dental arches deviating from strict ideal norms. Such deviations may be small rotations only or slightly tipped teeth. In other cases the deviations are so marked that it is justified to term the dentition a malocclusion. Not all these deviations and malocclusions need to be corrected. Hence it is important to be able to decide when it is beneficial for the patient to receive orthodontic treatment. A decisive factor in the evaluation of the treatment need is patients' perception of malocclusions. Investigations have shown that most patients initiate orthodontic treatment after consulting their regular dentist. It is important that the latter are updated about treatment indications and potential. In the present paper the recent documentation on orthodontic treatment need is described and discussed. PMID- 2247366 TI - [Does orthodontic treatment affect craniofacial growth?]. AB - Orthodontic treatment can influence growth of maxilla and mandible, and give better harmony of the skeletal components of the face. However, choice of an inappropriate treatment method can deteriorate the balance of the upper and lower face. It is probably easier to influence the sutural growth than the growth of the condylar cartilage. It is possible both to increase the width of the maxilla and to increase, respectively decrease, forward growth of the maxilla. Even if the amount of growth in the condyle cannot be significantly influenced, the position of the mandible in relation to the rest of the face can be indirectly influenced by control of the sutural growth. PMID- 2247367 TI - [New treatment modalities for patients with cleft lip, jaw and palate]. AB - Cleft lip/palate patients are reported at birth to a national register and are referred to one of the cleft palate teams in Oslo or Bergen. The teams coordinate the active treatment periods by plastic surgery, orthodontics/jaw orthopedics, logopedics, otology, pediatrics, psychology and orthognatic surgery. Presurgical orthopedics is performed early after birth in some total clefts with very asymmetric jaw segments. Lip is closed at 3 months, hard and soft palate at 1 1/2 years. Only a few cases now need early protraction of the upper jaw due to growth restraint. Many need orthodontic repositioning of the jaw segments and establishment of good occlusion. Bone from the ileac crest is grafted to the cleft prior to eruption of the canine. This permits normal development of the alveolar bone and eruption or, if the lateral is missing, orthodontic mesialization of the canine, excluding prosthetic replacement. PMID- 2247368 TI - [Dental awareness among young adults]. AB - Awareness of own dental appearance was studied in 150 18-year old individuals by assessing their ability to identify a photograph of own teeth among 17 alternative photographs. More than two thirds of the subjects identified their picture on first trial, which reflects a high level of dental awareness in the group. Consciousness about dental arrangement was high as 56% reported deviating tooth position as a primary cause for recognition. Other features, such as tooth morphology, discolouration and fractures were stated as reasons for identification by 26% of the individuals. The findings indicate that young adults are able to recognize a good orthodontic treatment result. Therefore, a high standard of the treatment delivered seems to be justified by the level of dental awareness in young adults. PMID- 2247369 TI - [New experimental procedures in adult orthodontics]. AB - This presentation discusses a new approach to preprosthetic orthodontic treatment of adult patients with missing anterior teeth. The basic idea is: Prosthodontic appliances with high and lasting esthetic qualities are difficult to obtain in the anterior region. Our alternative is to close anterior gaps by orthodontic treatment, if necessary combined with recontouring of individual crowns by means of grinding and/or light-cure resin buildup. Spaces needing prosthetic closure are transferred to more posterior regions of the dental arch, usually in the premolar region. Different aspects of this new approach has been presented and discussed. The material is derived from a clinical study currently in progress at the departments of orthodontics and prosthetics at The Dental Faculty in Oslo. PMID- 2247370 TI - [Treatments of major skeletal anomalies in adults]. AB - This article deals with orthodontics and maxillofacial surgery as an integrated treatment. During the last fifteen years orthognathic surgery has made extensive progress, and almost all great malocclusions combined with facial anomalies can be treated with good and stable results. Because the surgical methods are more refined and sophisticated, greater demands have been put on the planning of the treatment making this a team effort between the orthodontist and the surgeon. Treatment of anterior crossbite, extreme overjet and open bite are shown as examples of what can be achieved by this team approach. The outlines of the treatment are given and it is stressed that the orthodontic treatment must be done with fixed appliances. The complications are few, and the results are usually stable. This integrated treatment can therefore be recommended to those patients who are motivated for it and really need it. PMID- 2247371 TI - Immunocytochemical evaluation of neoplastic and non-neoplastic breast diseases with Mab A-80. AB - Five hundred breast tissue samples from 404 cases were immunostained with A-80, a murine IgM Mab that recognizes a mucinous glycoprotein associated with exocrine differentiation. Samples included 196 primary breast carcinomas, 30 breast carcinoma metastases, 118 fibrocystic disease (FCD), and a further group of 84 samples of FCD from cases known to have breast carcinoma. These samples represented a broad spectrum of common and rare variants of carcinoma and FCD. Samples of fibroadenomas, lactating adenomas, cystosarcoma phylloides, gynecomastia, and normal breasts were similarly studied. The vast majority of carcinomas, 203/212 (95.7%) were immunoreactive; staining varied in extent and intensity, and was virtually unrelated to histologic type and to the presence or absence of recognizable glands. In samples including in-situ and infiltrating ductal or lobular carcinoma, reactivity was frequently stronger in the infiltrating components. No significant difference in reactivity between primary and metastatic carcinomas was noted. Of the group of 118 FCD, 27 were negative whereas 91 showed focal and weak staining. Seventy-two/84 FCD with associated carcinoma were immunostained; in 13 of those 72, staining was strong and extensive. Fibroadenomas, lactating adenomas, gynecomastia, and normal "resting" and lactating breast samples stained focally or not at all. Our findings indicate that Mab A-80 is an excellent immunohistochemical marker for the overwhelming majority of breast carcinomas whereas it marks weakly or not at all the majority of benign neoplasms and normal breast. Moreover, Mab A-80 recognizes a subset of FCD that includes proliferative variants associated with an increased incidence of carcinoma, and FCD in association with carcinoma. Questions regarding rare breast carcinomas that do not react with Mab A-80 remain unclear; yet, we believe that Mab A-80 is a highly promising marker of malignant and dysplastic breast epithelium. PMID- 2247372 TI - Superficial esophageal carcinoma. With special reference to basaloid features. AB - A total of 200 surgically resected esophageal carcinomas were reviewed and 50 cases (25.0%) were identified as "superficial esophageal carcinoma" (depth of invasion limited to mucosa or submucosa). The age, sex, location, tumor size, histological features, and prognosis were studied in 49 of these cases. The carcinomas were classified into four histological groups: 1) squamous cell carcinoma (SCC), 2) squamous cell carcinoma with basaloid features and expansive growth (BE), 3) squamous cell carcinoma partially mixed with the basaloid type (mixed), and 4) other types of tumors. There were 25 cases (51.0%) of SCC, 14 BE cases (28.6%), 8 mixed cases (16.3%), and 2 (4.1%) other tumors (malignant melanoma, adenoacanthoma). Among 133 advanced cancers (invasion into and beyond the muscularis propria), there were 123 cases (92.4%) of SCC, 9 (6.8%) mixed cases, and one (0.8%) adenoacanthoma. No BE lesions were identified. In superficial carcinoma there was a statistically significant difference between BE and mixed carcinoma by the chi-square test (p less than 0.05) with regard to the maximum longitudinal diameter. None of the BE carcinoma showed nodal metastasis, while 3 (12.0%) of SCC and 5 (62.5%) of mixed lesions had nodal metastases. The difference in cumulative survival rate between BE and mixed carcinoma was statistically significant by the Z and Wilcoxon tests (p less than 0.05). We conclude that the BE type of superficial esophageal carcinoma had a better prognosis, and should be separated from the ordinary SCC with infiltrative growth from a clinicopathological view point. PMID- 2247373 TI - Chorioangiomas of intermediate size and intrauterine growth retardation. AB - Very large chorioangiomas are a rare but well recognized cause of neonatal morbidity, while small ones are clinically insignificant. This study emphasizes that some chorioangiomas of intermediate size may be causally related to intrauterine growth retardation, and that they may be surprisingly difficult to detect in the unfixed placenta. PMID- 2247374 TI - Stereotactic biopsy diagnosis of primary non-Hodgkin's lymphoma of the central nervous system. A histological and immunohistochemical study. AB - We report 29 cases of primary non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS), 26 of which were diagnosed by stereotactic biopsy and 3 by autopsy. In seven cases the patients were affected by AIDS. Histological examination of this series revealed 15 cases of immunoblastic lymphoma, 12 cases of centroblastic lymphoma, 1 case of lymphoplasmacytic immunocytoma and 1 case of unclassified high grade lymphoma. By immunohistochemistry the B-cell origin of lymphoma cells was demonstrated in 28/29 cases. Eight cases were assigned to the B-cell lineage by demonstration of monotypic surface or cytoplasmic immunoglobulin or of the B-cell phenotype CD22+, CD2-, CD3-, CD5-. In twenty cases the B-cell nature of lymphoma was identified by positivity with two or more anti-B monoclonal antibodies (LN1LN2MB2) and negativity by the anti-T monoclonal antibody UCHL1. The histologically unclassified case was a peripheral T-NHL (CD1 , CD2+, CD3-, CD5+, CD22-). We conclude that histological and immunohistological evaluation of stereotactic biopsy specimens provides sufficient information for diagnosis and phenotypic characterization of primary NHL of the CNS. These lymphomas exhibit important predominance of high-grade malignancy histological types and are nearly always B-cell derived. In addition, we provide further evidence that the panel of monoclonal antibodies LN1, LN2, MB2, and UCHL1 is useful for immunophenotypic characterization of brain lymphomas when only paraffin embedded stereotactic biopsy tissue is available. PMID- 2247375 TI - Computer simulation of tumor cell motility and proliferation. AB - Tumor growth is considered to depend on tumor cell proliferation and on tumor cell motility. The present study investigates in which way these two cellular properties influence the evolving morphological pattern. Computer simulations were performed, where cells were either dividing or moving for a variable distance at a present probability. The simulation parameters (probability of motility, maximum moving distance) were set interactively. The resulting patterns were evaluated by binary morphological criteria, 13 of 17 binary criteria showed a significant relationship with the simulation parameters (median test: p = less than 0.05). Discriminant analysis of two sets of simulations with different simulation parameters provided a correct classification with an efficiency of 100% (k-nearest-neighbour method; jack-knife-procedure). The results indicate that cell proliferation and motility affect morphological patterns in a reproducible way and that the patterns in turn provide morphological clues for the quantitative estimation of motility and proliferation. PMID- 2247376 TI - Similarities between neuronal Lewy bodies in parkinsonism and hepatic Mallory bodies in alcoholism. AB - The aim of the present study was to identify components of the Lewy body, which is a characteristic neuronal lesion in idiopathic Parkinsonism, using histochemical methods that selectively stain the Mallory body, a characteristic lesion of the hepatocyte in alcoholism. Our observation that Lewy bodies stain with phosphotungstic acid hematoxylin, the dye originally used for demonstrating alcoholic hyaline (Mallory bodies), promoted this study. The material consisted of formalin-fixed, brain stem tissue from Parkinsonian subjects, and of similarly preserved liver tissues from alcoholic individuals. The methods selected were Roque's chromotrope 2R-aniline blue, and Liisberg's rhodamine B, which stains Mallory bodies due to its affinity for sites of tissue keratinization. Hence, skin was also included in this study as control tissue. Our results showed that Lewy bodies in the brain, Mallory bodies in the liver and stratum corneum in the skin have identical staining properties with the dyes used, indicating the presence of histochemically similar components. Taking into account the reactions of these dyes with model substances, we suggest that the similar components shared by Lewy bodies and Mallory bodies are arginine-rich proteins and lipids associated with keratinization. Similar findings in both, a toxin-induced lesion of the liver, and a spontaneous lesion of the brain may offer clues for understanding the latter's mode of formation. PMID- 2247377 TI - Histology of the lower intestinal tract in Crohn's disease of children and adolescents. Multicentric Paediatric Crohn's Disease Study. AB - Serial sections of 1047 colonic and rectal biopsies from 385 children and adolescents suffering from Crohn's disease were studied histologically. Inflammatory alterations were seen in 76% of the biopsies and 84% of the patients. Incidence of inflammatory infiltration, of crypt abscesses, of erosions, and of ulcers decrease from caecum to rectum were studied. The incidence of granulomas falls along the colon but rises in the rectum. The occurrence of granuloma depends rather on the severity of the inflammation than on the biopsy site. Granulomas are present in 26% of the biopsies and 42% of the patients. Compared to adults, the incidence was twofold in children. Discontinuous type of infiltration, density of infiltration, crypt abscesses, rectal erosions prevail in children, diffuse type of infiltration, and colonic ulcers in adults. Incidence of granulomas is reduced after the second year of illness and after the 16th year of life. The number of granulomas per mm3 biopsy is increased in children, their average size in adults. PMID- 2247378 TI - Are there characteristic alterations in lung tissue associated with Crohn's disease? AB - Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis. PMID- 2247379 TI - Histoplasmosis duboisii (African histoplasmosis). An African case reported from Chile with ultrastructural study. AB - A case of histoplasmosis duboisii in a 30 year-old engineer is presented. The diagnosis was made with the help of light microscopy, electron microscopy and cultures. Although diagnosed in Chile, the patient probably acquired the disease in the endemic African area, more precisely in the Ivory Coast. Differential diagnosis between Histoplasma capsulatum var. capsulatum and Histoplasma capsulatum var. duboisii is based primarily on the larger in-vivo yeast form size of the latter. Electron microscopy study, the first done on the duboisii variety of Histoplasma capsulatum in human material to our knowledge, was not essential for this purpose. Differential diagnosis between Histoplasma capsulatum var. duboisii and Blastomyces dermatitidis is based on morphological tissue changes and mycologic characteristics. Once more, a case of an "exotic" or geographically restricted disease is detected far from its endemic area, thanks to easier means of transportation. Earth is a shrinking planet. PMID- 2247380 TI - Unusual bony lesions of histiocytosis X in a patient previously treated for Hodgkin's disease. AB - We present an unusual case of multifocal Histiocytosis X in a 78-year-old man treated for Hodgkin's Disease 33 and 24 years previously. The Hodgkin's Disease at first involved cervical nodes and 9 years later axillary and inguinal nodes and was treated by radiotherapy. Chronic destructive lesions developed in the femora and pelvis and bone biopsies showed a curious mixture of fibroblastic tissue and foamy macrophages. These lesions eventually resulted in pathological fractures of the femoral necks, and bilateral hip replacements were required seven years after initial detection of the bony lesions. There was a focal infiltrate of S-100 protein positive histiocytic cells containing Birbeck granules in the femoral heads. There was radioisotopic and radiological evidence of other skeletal lesions. The association between Histiocytosis X and Hodgkin's Disease is recognised but rare and its significance is discussed. PMID- 2247381 TI - What's new in the mechanisms of host resistance to Candida albicans infection? AB - Despite extensive investigation, the mechanisms of host resistance against C. albicans infection remain poorly understood. Granulocytes and macrophages are the major effector cell types; however, their intrinsic candidacidal activity is rather limited, and its full expression requires augmentation by components of the T cell-initiated lymphokine cascade. Consequently, susceptibility to recurrent mucocutaneous infections may be associated with aberrant T cell function. In contrast, protection from systemic infection appears to be mediated by candida-specific antibodies. PMID- 2247382 TI - What's new in cytoskeleton-organelle interactions? Relationship between microtubules and the Golgi-apparatus. AB - Several biochemical processes in animal cells are confined to distinct membrane bounded compartments. Segregation of specialized functions into different compartments necessitates intercompartment transfer of material. This transfer is mediated by carrier vesicles which, by precise sorting and transport mechanisms, are targetted to their correct destinations. Microtubules, major constituents of the cytoskeleton, are involved both in these intracellular transport processes and in the spatial organization of cytoplasmic organelles. Accumulating evidence suggests that various classes of membranous organelles interact with microtubules. The positioning of several organelles, including the Golgi apparatus and lysosomes, depends on an intact interphase microtubule network. Furthermore, it has been shown that many of these organelles, for example Golgi elements, tubules of the endoplasmic reticulum, exocytic or secretory vesicles and lysosomes move along microtubules. In this article we will discuss the role of microtubules in the movement and positioning of elements of the Golgi complex. The first part will summarize structural and functional aspects of microtubules and the Golgi apparatus and review evidence for their interaction. In the second part, the possible physiological relevance of this interaction will be discussed and correlated with other membrane-microtubule interactions. Finally, emerging questions and perspectives in this field are outlined. PMID- 2247383 TI - Hypochromic reticulated streaks in incontinentia pigmenti: an immunohistochemical and ultrastructural study. AB - A 25-year-old woman who recently gave birth to a baby affected by classic lesions of incontinentia pigmenti (IP), had hypochromic, atrophic, and reticulated streaks on both lower limbs. Her personal history was unremarkable for IP, and physical examination revealed no other cutaneous signs of the disease. Immunohistochemical and electron microscopic studies were performed on biopsies obtained from both normal and hypochromic skin of the leg. Hypochromic skin showed epidermal atrophy and lack of adnexae, without significant melanocyte abnormality. As demonstrated by this patient, hypochromic reticulated streaks can represent the only cutaneous marker of IP in adulthood. Careful search for such skin lesions in the mother of a child with IP is essential in order to ascertain whether there is a risk of its occurrence in future offspring. PMID- 2247384 TI - Diaper performance: maintenance of healthy skin. AB - Skin wetness is proportional to diaper wetness, and with increased skin wetness, the potential for diaper dermatitis is increased. This study evaluated a wide range of infant diaper products. Eighty healthy volunteers wore 2-inch wetted diaper patches on their volar forearm for two hours. An evaporimeter was used to measure excess skin wetness attributed to the patches. The amount of moisture retained in the patch was also calculated. We found that superabsorbent (SA) disposable diapers kept the skin drier and retained more synthetic urine than cloth reusable and conventional disposable brands, and thus have the greatest potential for helping prevent diaper dermatitis. The SA brands evaluated did an equally adequate job in keeping the skin dry and in retaining moisture. Conventional disposable diapers were less able to keep the skin dry than SA diapers and were not superior to cloth products in most instances. Cloth diapers' performance depended on their composition. Those with several layers of the same fabric were less successful in keeping the skin dry than ones that contained middle layers of different nonwoven components. PMID- 2247385 TI - Osteomyelitis caused by nail biting. AB - Nail biting is a common habit in children. In most cases, it is of cosmetic concern only; however, if not controlled, it can lead to serious morbidity. A case is presented of a child who developed osteomyelitis of a distal phalanx as a result of chronic nail biting. PMID- 2247386 TI - Papulonecrotic tuberculid in a 9-year-old American girl: case report and review of the literature. AB - Papulonecrotic tuberculid is a rare cutaneous manifestation of tuberculosis that can also be associated with other mycobacteria. Clinically, it is an asymptomatic, recurrent eruption of papules with a necrotic center in a symmetric, acral distribution. Tubercle bacilli are not present in skin biopsies. The eruption resolves promptly with antituberculoid therapy. Few patients with this entity have been reported in the United States over the last 50 years. We report a 9-year-old, otherwise healthy, American girl whose sole initial findings were lesions of papulonecrotic tuberculid secondary to Mycobacterium tuberculosis. PMID- 2247387 TI - Granuloma gluteale infantum: case report and review of the literature. AB - Granuloma gluteale infantum, a benign granulomatous eruption involving the gluteal region, histologically shows a nonspecific dermal inflammatory infiltrate composed of neutrophils, lymphocytes, histiocytes, plasma cells, and eosinophils. It is important to recognize this condition, as it may clinically simulate a neoplastic process. It arises as a complication of primary irritant diaper dermatitis, however, and typically resolves without treatment. PMID- 2247388 TI - Congenital midline hamartoma: case report with histochemical and immunohistochemical findings. AB - We report the case of a polypoid nodule on the chin of an infant. Microscopically, the lesion featured numerous pilosebaceous units, eccrine sweat glands, arrectores pilorum muscles, mature adipose tissue, and prominent admixtures of skeletal muscle. This lesion has much in common with the accessory tragus, and is similar to the one reported earlier as rhabdomyomatous mesenchymal hamartoma. We feel the more general term congenital midline hamartoma is preferable, as it encompasses both the clinical and microscopic features of the lesion. PMID- 2247389 TI - The association of keratosis pilaris atrophicans with hereditary woolly hair. PMID- 2247390 TI - Preschool sarcoidosis masquerading as juvenile rheumatoid arthritis: two case reports and a review of the literature. AB - Preschool sarcoidosis is characterized by the triad of skin, joint, and eye disease without pulmonary involvement. Arthritis and uveitis are also frequently seen together in juvenile rheumatoid arthritis. We report two patients with preschool sarcoidosis, both of whom were initially diagnosed and treated as having juvenile rheumatoid arthritis. Skin biopsy is an important early diagnostic procedure to differentiate the conditions. The uveitis in both diseases can have serious sequelae. PMID- 2247391 TI - Guide to information for families with inherited skin disorders. PMID- 2247392 TI - Dysplastic nevi in children. AB - Issues surrounding the diagnosis and management of the dysplastic nevus have sparked considerable controversy in the dermatologic literature. Despite the great amount of attention to this subject, little has been written about the problem as it relates to the pediatric patient. For this reason, we formulated a set of questions that we thought needed to be addressed, and sought answers from several dermatologists. The replies largely reflect personal opinions, as few data are available on which to base a standard approach to these lesions. PMID- 2247393 TI - Hypohidrotic ectodermal dysplasia. PMID- 2247394 TI - Autosomal recessive inheritance of hypohidrotic ectodermal dysplasia. PMID- 2247395 TI - Medical audit. Introduction. PMID- 2247396 TI - Medical audit. Proceedings of a meeting. 3 November 1989. PMID- 2247397 TI - The organization of medical audit at District level (medical specialties). PMID- 2247398 TI - Experience in medical audit: general practice. PMID- 2247399 TI - Practical principles of medical audit. AB - The practical principles have been highlighted to help doctors avoid pitfalls in audit, especially when starting to carry out formal systematic audit. As these principles are mastered, audit activity can be expanded as desired with a firm and appropriate basis established for the activity. PMID- 2247400 TI - Quality assurance in other contexts. PMID- 2247401 TI - Quality assurance in other contexts--'total service'. PMID- 2247402 TI - Medical audit in the current climate. PMID- 2247403 TI - Making audit truly educational. PMID- 2247404 TI - Managerial implications of medical audit. PMID- 2247405 TI - Clinical audit experience in the South West Region. PMID- 2247406 TI - Feed restriction of turkey breeder hens--a review. AB - Past research on feed restriction methods with turkey breeder hens has involved the feeding of 1) high-fiber or low-energy diets, 2) low dietary protein, 3) limited quantities of feed, 4) rations on a skip-a-day program, 5) distasteful compounds, or 6) combinations of these methods. In general, feed-restricted turkey breeder hens showed a reduction in BW and a delay in sexual maturity at time of lay with no effect on fertility, hatchability of fertile eggs, and hatchability of all eggs set. Egg weight was unaffected in 13 studies, but decreases and increases were reported for two and three studies, respectively. The results on egg production and feed efficiency (number of eggs/unit of feed) were more variable. Egg production decreased, increased, or had no effect in 6, 2, and 14 of the feed restriction programs, respectively. Feed efficiency of restricted hens either was poorer (two reports), improved (three studies), or had no effect (six studies). The larger parent-stock breeder candidate of today may not respond to these feed restriction programs in the same manner as the breeder hens of the 1970s and early 1980s. Most likely, more severe feed restriction programs will have to be designed to lower the BW of these larger hens. PMID- 2247407 TI - Influence of age at final beak trimming on pullet and layer performance. AB - Effects of final beak trimming on pullet and layer productivity were examined with three strains of commercial layers. All pullets were precision-trimmed at 7 days with final beak trimming at either 63, 84, or 105 days. Transient depressions of pullet body weight and feed consumption were noted in the periods immediately following beak trimming. Pullet mortality from 7 to 18 wk of age and 18-wk body weight were not significantly affected by beak trimming treatments. Strain effects were noted in rate of feed consumption following beak trimming. Age at 50% production was significantly later among birds trimmed at 63 days than among those trimmed at 84 or 105 days. Feed consumption, egg production, and mortality (140 to 441 days) were significantly lower among birds trimmed at 63 days than among those trimmed at 84 or 105 days. Egg quality and size were not influenced by beak trimming treatments. PMID- 2247408 TI - Evaluation of colony size and cage space for laying hens (Gallus domesticus) using fuzzy decision analysis. AB - A replicated experiment (two, 1-yr trials) was conducted to define colony size and cage space requirements of laying hens. DeKalb XL pullets, 19 wk of age, were randomly assigned to cages sized 1548, 3097, and 4645 cm2 at population densities of 2, 3, 4, or 5 hens. Membership values for fuzzy decision analysis were related to the performance of birds as measured by hen-day production and cumulative mortality. The decision analysis showed the crossover point between an uncrowded and a crowded condition was 3 birds in both trials for cage sizes of 1548 and 3097 cm2 based on maximin [corrected] decision values. The crossover point for the largest cage area (4645 cm2) differed between 3 and 4 birds for Trials 2 and 1, respectively. This suggested crowding pressure was not as great when more space was available to the birds. PMID- 2247409 TI - Selection for resistance to monensin, nicarbazin, and the monensin plus nicarbazin combination. AB - Two series of experiments were conducted to assess the relative ability of strains of Eimeria acervulina and Eimeria tenella to develop resistance to monensin (MON), nicarbazin (NIC), and the monensin plus nicarbazin combination (MON plus NIC). The studies were designed so that drug concentrations in the selection experiments were increased whenever possible. During selection, E. acervulina increased its reproductive index in the presence of NIC or MON plus NIC, equivalent selection in the presence of MON resulted in only a slight increase in reproductive ability. Eimeria tenella, however, was unable to increase its reproductive capacity to the respective drugs. Sensitivity tests after 60 generations of selection revealed that patterns of resistance development for E. acervulina and E. tenella corresponded with the changes in reproductive indices established in the selection experiments. Thus, results of these tests indicate that E. acervulina possesses the ability to develop resistance to NIC and MON plus NIC. Under essentially the same conditions of selection, E. tenella developed only partial resistance to the respective drugs. PMID- 2247410 TI - The utilization of brewers' dried grains in the diets of Chinese ringneck pheasant-breeder hens. AB - Two trials were conducted, each one using 240 Chinese Ringneck pheasant-breeder hens (Phasianus colchicus torquatus) to determine the effects of feeding various levels of brewers' dried grains (BDG) on egg production, fertility, hatchability, and feed consumption. The birds were subjected to natural daylight. Data were collected for 16 wk of egg production (April 1 through July 31). Each of four diets containing 0, 15, 30, or 45% BDG was fed to three pens (19 females and 1 male per pen), beginning 1 wk prior to the onset of lay. The eggs were collected twice daily and were stored at 13 C and were set in incubators every 14 days. The eggs were candled on Day 21 of incubation to determine the number of infertile eggs and dead embryos. The hatch was removed on Day 25. The egg production and fertility from BDG-fed hens did not differ from those of the control hens. The hatchability of fertile eggs was higher (P less than .05) from hens fed diets containing 30 and 45% BDG than from hens fed the control diet. The inclusion of BDG in the diets of pheasant-breeder hens had a favorable influence on the hatchability of eggs. PMID- 2247411 TI - Effect of calcium and phosphorus on the incidence of leg abnormalities in growing broilers. AB - Experiments were conducted to determine the effect of various dietary levels of Ca and P on growth and leg abnormalities in broiler cockerels fed corn and soybean meal diets varying in Ca and P content. Experiment 1 was a 2 x 4 factorial arrangement utilizing .77 and .97% Ca and .33, .38, .43, and .48% available (non-phytate) P (AP). The higher level of Ca reduced the growth rate of chicks fed low levels of AP. Neither Ca nor AP affected the incidence of crooked legs or dyschondroplasia. Increasing AP to .43% increased (P less than .05) the percentage of bone ash and bone weight. In Experiment 2, chicks were reared for 3 wk on diets containing either .40 or .50% AP. From 3 to 6 wk of age, the chicks were fed diets containing from .25 to .50% AP. The Ca:AP ratios were 2:1 in all diets. The level of AP in diets fed to 3 wk of age had no influence on chick growth, the incidence of crooked legs, or dyschondroplasia in either the starting or growing period. In Experiment 3, the chicks were reared in environmental chambers and from 3 to 6 wk of age and exposed to either constant temperature (27 C) and relative humidity (RH) (50%) or cyclic temperature (27 to 38 C) and RH (80 to 50%). The chicks were fed diets containing either .30% AP and .60% CA or .45% AP and .90% Ca from 3 to 6 wk of age. Cyclic temperature and higher RH depressed growth (P less than .05) but had no effect on the incidence of weak legs or dyschondroplasia. PMID- 2247412 TI - Sunflower meal as a component of fat-supplemented diets for broiler chickens. AB - An experiment was conducted to determine the influence of diets containing sunflower meal (SFM; 32.6% protein and 18.4% crude fiber) with and without supplemental animal-vegetable (A-V) fat on performance of broiler chickens. A complete factorial arrangement of three levels of SFM (0, 10, or 20%) and two levels of A-V fat (0 or 6%) was used. Diets were fed for ad libitum access to broilers from 1 day to 7 wk of age. Body weight, feed consumption, and MEn of the diets were determined at 4 and 7 wk of age. Results show that the inclusion of 10 or 20% SFM had no effect on body weight gain but impaired (P less than .01) feed efficiency (FE; kilograms of feed consumed per kilogram of gain). The use of 6% A V fat in the diet increased (P less than .01) weight gain and improved (P less than .01) FE at all levels of SFM in the diet. The extent of improvement in FE caused by 6% A-V fat was greatest with the 10% SFM diet. Nitrogen-corrected metabolizable energy decreased with each 10% increment of SFM and increased with the inclusion of 6% A-V fat in the diet; no interactions were observed. PMID- 2247413 TI - Regulation of lipid metabolism by dietary sorbose in laying hens. AB - Single Comb White Leghorn laying hens received ad libitum diets (10 birds per diet) containing varying concentrations of sorbose (0, 100, and 200 g/kg diet) for 4 wk. Body weight gain and feed intake decreased with increasing dietary sorbose. Serum triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein, and chylomicron levels were significantly reduced, in dose dependent fashions, as dietary sorbose increased, whereas serum glucose level remained unchanged by the dietary regimens. Absolute and relative weights of abdominal fat were also decreased by increasing dietary sorbose. Liver color improved; it became less white and less yellow with the supplement of dietary sorbose. Hen-day egg production rate was not affected with dietary sorbose, and hence, it has been shown that dietary sorbose can be used as a potential regulator of lipid metabolism in the laying hen. PMID- 2247414 TI - The effects of energy and amino acid levels on performance and carcass quality of male and female broilers grown separately. AB - Studies were conducted to evaluate the response of male and female broiler chickens to diets containing different levels of energy and amino acids. Two energy series were compared: 3,080, 3,135, and 3,190 kcal of ME/kg ("low") and 3,190, 3,245, and 3,300 kcal of ME/kg ("high") in pelleted starter, grower, and finisher diets. Diets provided a minimum of 85, 90, 95, 100, 105, and 110% of suggested amino acid recommendations for the broiler male except for Met and TSAA, which were kept at 105%. Modifications were made in feeding periods, recognizing the differences in rate of gain and marketing ages of the two sexes. Feeding periods were 0 to 21, 21 to 42, and 42 to 56 days for males and 0 to 18, 18 to 35, and 35 to 49 days for females. Four floor pen trials utilizing 9,600 male and 9,600 female broilers were conducted. Birds were processed to determine dressing percentage and abdominal fat pad weights. Energy content of the diets had no significant (P greater than .05) effect on body weight or feed efficiency for male or female broilers. Carcass dressing percentage of females, but not males, was significantly (P less than .05) increased on the high energy series. Abdominal fat pad was not influenced by energy for either sex. For both sexes, increasing dietary amino acid levels resulted in significant (P less than or equal to .05) linear improvements in live weights and feed utilization and a reduction in abdominal fat pad weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247415 TI - Effects of feed restriction during the rearing period and age at photostimulation on the reproductive performance of turkey hens. AB - An experiment with Nicholas parent-stock turkey breeder hens was designed to determine the effects of feed restriction during the rearing period and age at photostimulation on reproductive performance. Hens reared on ad libitum intake of conventional corn-soybean diets (ad libitum), skip-1-day per week (skip-1-day), and 95% of ad libitum (95%) were placed into cages and photostimulated when they reached a target body weight of 10 kg or at the conventional age of 29 wk. A 3 x 2 factorial design was used, with five replicates of three hens for each treatment. All birds were fed for ad libitum access during the breeding period. More eggs were set from 95% birds than from ad libitum or skip-1-day birds (P less than .05); there was no difference between ad libitum and skip-1-day birds. Photostimulating based on 10 kg of BW versus 29 wk of age had no effect on total eggs set. There was no effect of rearing feed restriction on fertility or hatchability. Photostimulating based on 10 kg rather than 29 wk of age reduced fertility and hatchability (P less than .05). The results of this study indicate that optimum reproductive performance is attained by restricting the feed consumption of turkey breeder hens to 95% of ad libitum during the rearing period. No benefits were gained from photostimulating at 10 kg of BW versus 29 wk of age. PMID- 2247416 TI - Effect of dietary lactate and glucose on the incidence of sudden death syndrome in male broiler chickens. AB - An experiment with a factorial arrangement of treatments using four levels of dietary lactate (0, 2.5, 5.0, 7.5% calcium lactate) and four levels of dietary glucose (0, 15, 30, and 45% cerelose) was conducted to determine the effect of these compounds on the incidence of sudden death syndrome (SDS) in 1,280 male broiler chickens reared in battery brooder cages to 4 wk of age. Overall mortality was 6.64% of which 32.9% (or 2.19% of broilers housed) was attributed to SDS. There were no significant differences between treatments in either total mortality or mortality due to SDS. PMID- 2247417 TI - Determination of available amino acids and energy in alfalfa meal, feather meal, and poultry by-product meal by various methods. AB - Several experiments were conducted to evaluate various methodologies for determining availability of amino acids (AA) and energy in alfalfa meal (AM), feather meal (FM), and poultry by-product meal (PBPM). Digestibility of AA was determined with 48-h precision-fed cockerel assays using conventional (CONV) and cecectomized (CEC) cockerels. Amino acid bioavailability was assessed with chick growth assays. True digestibility values of most AA were significantly lower for CEC than for CONV cockerels. In the chick growth assays, partitioning weight gains to reflect only growth attributable to supplemental crystalline AA or test feedstuff AA consumption often yielded higher bioavailability values than when total weight gains were used for FM and PBPM but lower ones for AM. The magnitude of differences between AA digestibility (cockerels) and AA bioavailability (chicks) values varied among feedstuffs; the largest differences were observed for FM. The TMEn values of AM and PBPM were lower for CEC birds than for CONV birds, whereas TMEn of FM was similar for both types of birds. PMID- 2247418 TI - Turkey muscle growth and focal myopathy. AB - Muscle structure and blood enzyme activity were studied to 16 wk of age in lines of turkeys selected for rapid growth. The body and carcass weights were measured, frozen sections of breast and leg muscles examined, and plasma creatine kinase (CK) levels determined. Muscle weights were usually proportional to BW except for the relatively larger superficial pectoralis (SP) muscles in the most rapidly growing line. Damaged muscle fibers were found in all muscles examined, especially in the SP of the breast, the gastrocnemius (GA), and other muscles of the leg; these damages became more common from 10 to 16 wk of age. There were more degenerating muscle fibers and higher levels of plasma CK in the rapidly growing lines than in a slower growing unselected line. The findings support the idea that a focal myopathy, unrelated to deep pectoral myopathy or to inherited muscular dystrophy of the chicken, is associated with rapid growth of turkeys. PMID- 2247419 TI - Effects of tetraphenylboron on the motility, oxygen consumption, and adenosine 5' triphosphate content of fowl spermatozoa. AB - The effects of tetraphenylboron on the motility and metabolism of fowl spermatozoa at 30 C were investigated. The motility of intact fowl spermatozoa was reduced by tetraphenylboron at concentrations that had little effect on the oxygen consumption and adenosine 5'-triphosphate content of spermatozoa. The inhibition of motility was reversed by the removal of tetraphenylboron. Furthermore, the addition of tetraphenylboron improved the maintenance of spermatozoa during storage. Tetraphenylboron did not affect the motility of demembraned spermatozoa, suggesting that the locus of action of tetraphenylboron is not directly on the axoneme of fowl spermatozoa. PMID- 2247420 TI - Half-life and metabolic clearance rate of recombinant-derived chicken growth hormone and purified turkey growth hormone in intact and hypophysectomized turkeys. AB - The half-life and metabolic clearance rate (MCR) of natural turkey growth hormone (tGH) were compared with those of recombinant-derived chicken growth hormone (rcGH) in intact and hypophysectomized (hypox) turkey poults at 8 and 13 wk of age. The hypox poults used were all hypophysectomized at 8 wk of age. The purpose of the experiment was to determine whether the source of growth hormone (GH) or the physiological changes associated with hypophysectomy might affect the disappearance of the hormone from the circulation and, hence, alter the biological response of the bird to exogenous GH. The mean half-life of GH in the growing turkey was 12.88 +/- .54 (SE) min. The source of GH had no effect on half life, and GH half-life did not vary significantly between poults sampled at 8 and 13 wk. Hypophysectomy significantly (P less than .01) increased the half-life of administered GH from 11.21 +/- .50 min in intact poults to 14.70 +/- .84 min in hypox poults. The MCR of GH in hypox poults 2 days following hypophysectomy was markedly lower than that of intact birds (1.08 versus 2.95 mL/min; P less than .001). The GH clearance in hypox birds increased during the 5 wk following hypophysectomy but still remained somewhat lower than that of intact birds (2.55 versus 3.00 mL/min; P = .06). The MCR of GH did not change in intact birds between 8 and 13 wk of age, and the MCR of rcGH and tGH did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247421 TI - Influence of diet-mediated maternal thyroid alterations on functional properties of turkey eggs. AB - Maternal thyroid status was altered by means of diet to determine its effect on functional properties of turkey eggshells. Hens were fed a control diet (CON), the CON diet containing .5 ppm triiodothyronine (T3), the CON diet containing 2.1 ppm iodine as potassium iodide (KI) or the CON diet containing .1% thiouracil (THIO). Feeding T3 decreased plasma thyroxine but elevated plasma T3 concentrations compared to CON. The KI diet had no effect on plasma thyroid hormone concentrations, but feeding THIO depressed plasma thyroxine with no effect on T3, resulting in an elevated ratio of the two hormones compared to the CON ratio. Feeding KI decreased egg volume and T3 increased egg density compared to CON, but no effects on egg weight, surface area, width, or length were noted. Dietary T3 depressed eggshell water vapor conductance compared to CON. Dietary iodine resulted in thinner eggshells with fewer pores than the CON, whereas THIO caused significantly more pores in eggshells than CON but had no effects on shell thickness. Dietary KI had no effects on maternal plasma thyroid hormone concentrations, suggesting that the effects were due to iodine availability rather than to thyroid hormones. It is concluded that the availability of iodine to turkey breeder hens may influence eggshell characteristics. PMID- 2247422 TI - Potential uses of combined halogen disinfectants in poultry processing. AB - Five organic N-halamine compounds (combined halogen disinfectants) were compared for their bactericidal activities against Salmonella typhimurium under controlled pH and temperature. All five compounds were effective as bactericides in demand free buffers ranging from pH 5.0 to 9.0 and treatment temperatures from 4 to 48 C. The range of contact times necessary for a 99.9999% inactivation of viable cells was from .22 to 29 min, depending on the halogen concentration, temperature, and pH of the demand-free buffer. Two of the compounds (3-chloro-4,4 dimethyl-2-oxazolidinone and 1,3-dichloro-4,4,5,5-tetramethyl-2-imidazolidinone) were found to have considerable promise in high-temperature applications, and a third compound (1-bromo-3-chloro-4,4,5,5-tetramethyl-2-imidazolidinone) was more suitable for low-temperature treatments. PMID- 2247423 TI - Microcidal effects of a new pelleting process. AB - The microcidal efficiency of a new pelleting process was evaluated in four trials. Also, different methods of measuring temperature and moisture were compared and attempts were made to determine the influence on efficiency of pH changes occurring during processing. In the new process, the traditional boiler conditioner was replaced by an Anaerobic Pasteurizing Conditioning (APC) System. Microcidal efficiency of the APC System, by itself or in conjunction with a pellet mill, appeared to be 100% against Escherichia coli and nonlactose fermenters, 99% against aerobic mesophiles, and 90% against fungi. These levels of efficiency were attained when the temperature and moisture of feed conditioned in the APC System for 4.6 +/- .5 min were 82.9 +/- 2.4 C and 14.9 +/- .3%, respectively. On-line temperature probes were reliable and provided quick, accurate estimates of feed temperature. The near infrared scanner and microwave oven methods of measuring moisture were much quicker but less accurate than the in vacuo method. There were no differences among the pH of samples of raw, conditioned, and pelleted feed. PMID- 2247424 TI - Age dependency of triiodothyronine-induced thermogenesis in young chicks: inhibition by propylthiouracil. AB - Age dependency of triiodothyronine (T3)-induced thermogenesis of young chicks at 1 and 2 wk of age was investigated by dietary administration of .5% propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis. Heat production measured by indirect calorimetry was increased by an intraperitoneal injection of T3, but the thermogenic effect was larger at 2 wk than at 1 wk of age. Heat production at 2 wk of age was decreased by PTU when the T3 was not administered, whereas the inhibitory effect of PTU was not found at 1 wk of age. It would appear, therefore, that little or no thermogenesis is responsive to exogenous T3 in young chicks at 1 wk of age even though the suppression of endogenous T3 is likely to occur by the PTU treatment. PMID- 2247425 TI - Presence and impact of Salmonella contamination in commercial broiler hatcheries. AB - Egg fragments from hatching trays, swabs of belting material, and paper pads from three broiler hatcheries were sampled for the presence and level of salmonellae. Salmonella serotypes were recovered from 71, 80, and 74% of the egg fragments, belting material, and paper pads, respectively. Overall, salmonellae were found in 75, 91, and 67% of the samples taken at Hatchery 1,2, and 3, respectively. Thirty-eight of 40 randomly selected samples contained greater than 10(3) salmonellae cells per sample. All of the Salmonella serotypes encountered in the present study had previously been isolated from poultry. The presence and persistence of salmonellae contamination in the hatchery suggests that the vulnerable day-of-hatch chick may be at a greater colonization risk in the hatchery than during grow-out. Contamination and penetration of the shell of hatching eggs may constitute the most important link (or critical control point) in the transmission of salmonellae to young birds and eventually the consumer. An effective intervention method may have to be employed at this point to break the transmission link and significantly impact the overall problem of Salmonella colonization in poultry. PMID- 2247426 TI - Composition of eggs from dwarf and normal chickens before incubation and at hatching in lines selected for 56-day body weight. AB - Comparisons of egg composition prior to incubation and when the chick had pipped through the shell were made for dwarf (D) and normal (N) chickens from lines selected for high (H) or low (L) body weight. Weight of moisture, ash, and fat decreased and nonlipid organic matter increased during incubation. The pattern for these components was the same on a percentage of egg weight basis except that there was no change in ash. Genotype by line interactions were significant for egg weight, moisture, ash, fat, and nonlipid organic matter before incubation and for all of these characteristics except fat at pipping. The interactions were due to values being lower for D than N in Line L, and D and N were similar in Line H. When egg component weights were expressed relative to egg weight, interactions were not significant prior to incubation but were present for moisture and fat at hatch. These data show that characteristics influenced by the sex-linked dwarfing gene are modified by the background genome. PMID- 2247427 TI - [Change in cardiovascular activation in learning and performance situations in children with learning disorders]. AB - A method is demonstrated for observing and statistically testing changes in cardiovascular activity in single cases between two types of situations, in this case a playing situation and a learning situation. Using this method it could be shown an abasement of cardiovascular activity during a learning situation together with their mother or father--compared to a playing situation--for 20 hyperactive children with learning problems of an average age of 9.7 years. Together with this abasement in cardiovascular activity there was observed a deterioration in the parent-child-relation. In the singles cases however it could be observed an abasement or an increase in cardiovascular activity. When the- often punishing--parent was replaced by a person who built up a positive relation to the child, there could be observed either an increase or an abasement or no change in cardiovascular activity, the effect being replaiable. The results point up to a critical examination of actual therapeutic concepts for children with learning problems. PMID- 2247428 TI - [Psychosocial management in medicine: a question of "management bias"?]. AB - It was Roth (1962) who first coined the term "management bias". This term served to brand a pervasive, uncritical identification of the social scientist's perspective in his research projects in medicine, with the problem definition of the medical orderer of research. Instead of unbiased findings he thus tended to affirm administrative categories, Roth argued. I will try to point out that problems like "management bias" are not exclusive to psychosocial science, but they may as well be found in the realm of psychosocial care. The chronically ill became more and more important as a person(ality) during the ongoing process of technical perfection of medical treatment. The intensively, technically supported medical treatment produces within its demands towards the patient and his social context a kind of "human failure", that is, the patient tends to not fulfill the highly demanding treatment tasks. Within psychosocial care, failure will rather be attributed to the personality or family pathology instead of the institutional setting, and in that way the scientific patterns of biased attribution will be repeated, thus revealing "management bias", thus supporting the institution's interest of not being blamed for failure. I'll describe the dynamics of the "management bias" and briefly point out aspects to overcome it. PMID- 2247429 TI - [Diagnosis and classification in the tension field between description and interpretation]. AB - Basic terms of medical and psychiatric classification are outlined in the introduction. This is followed by an historical sketch of German publications of early classification systems of child and adolescent psychiatry as found in the work of Tramer, Stutte, and Lutz. The main section deals with current classification systems. Deficits of the ICD-9 and recent improvements in the DSM III-R and the ICD-10 are discussed. The paper concludes with considerations regarding the empirical foundation of child and adolescent psychiatric disorders and with criticism of psychiatric classification in general. PMID- 2247430 TI - [Rumpelstilzchen on the couch--an ensemble of shame, identity and father themes]. AB - The fairy-tale "Rumpelstiltsken" is investigated as to its hidden meaning. A method, already described in the literature, is applied which allows conclusions about the hidden meaning to be drawn on the basis of the fairy-tale's place and handling with the history of literature. The hidden meaning found for "Rumpelstiltsken" lies in the question as to how individuation is possible in a symbiotic mother-child relationship. The answer is given in the fairy-tale in that a third person is introduced, who is, however, not involved in the symbiosis. A metapsychological concept of shame is then formulated on the basis of this understanding of "Rumpelstiltsken". PMID- 2247431 TI - Specific role of endopeptidases in modulating the nature of protein digestion products. AB - The impact of various endopeptidases on the nature of protein digestion products was measured with the digestion cell technique. After a 30 min pepsin pre digestion, casein and rapeseed concentrates were hydrolyzed with various amounts of pancreatin, trypsin and/or chymotrypsin. This hydrolysis was performed in a dialysis tube (molecular weight cut-off 1000) with continuous collection of the digested material. The addition of pure trypsin or chymotrypsin to pancreatin (Enzyme:Substrate 1:25) did not change the digestibility of casein. Only a higher pancreatin level (Enzyme:Substrate 1:12.5) increased the total protein digestibility without affecting the amino acid spectra. Rapeseed digestibility was markedly increased by the addition of pure trypsin to pancreatin. Lysine and arginine, target amino acids of trypsin, were favored at the expense of chymotrypsin and elastase target amino acids. Supplementation of pancreatin with chymotrypsin enhanced rapeseed digestibility without affecting the relative amino acid digestibility. The impact of a higher pancreatin ratio (Enzyme:Substrate 1:12.5) was similar to that of enriched pancreatin but the rate of amino acid release was modified. The differences between protein sources were mainly attributed to protein structure. PMID- 2247432 TI - Temporal variation in protein content and yield of Vigna mungo (L.) Hepper leaves. AB - Temporal variation in total protein and soluble protein contents and protein yield of Vigna mungo leaves at intervals of every three hours during day and night was studied. The study was done with the view to ascertain the hour of harvesting the leaves for maximum yield of leaf protein concentrate. Observations reveal that the total protein and soluble protein contents in the leaves are minimum during 3.00 to 6.00 hrs, which steadily rise with time to reach the maximum values during 12.00 to 15.00 hrs, after which the same shows a steady decrease with time. PMID- 2247433 TI - Changes in some nutrients of fenugreek (Trigonella Foenum graecum L.) seeds during water boiling. AB - Fenugreek seeds were boiled in water for various lengths of time (5, 10 and 15 min). Changes in weight, volume, moisture content, total sugars, nitrogen compounds, minerals, phosphorus compounds, phytic acid, amino acids and the in vitro digestibility of the seeds as well as the total solids of the boiling water were determined. Data indicated that there was an increase in both weight and volume as well as the in vitro digestibility of fenugreek seeds especially after the first 5 minutes of boiling. On the other hand, a decrease in the content of total sugars, protein compounds, calcium, magnesium, phytic acid, phosphorus and amino acids was observed. The reduction was accompanied by a gradual increase in the total solids of boiling water. PMID- 2247434 TI - Stability of fatty acids and leaf protein concentrate of Persian clover (Trifolium resupinatum). AB - Freeze-dried leaf protein concentrate (LPC) contained 18% lipids in which linolenic acid (61.5%) was the major component. Linolenic acid in LPC was almost stable when stored at ambient temperature (30 to 35 degrees C) and exposed to air for 24 weeks. Heating of LPC (50 to 200 degrees C) in presence of moisture (6 to 12%) progressively increased the rate of destruction of linolenic acid. Below 100 degrees C the presence of lipids did not affect the protein quality but at higher temperatures due to the lipid oxidation protein quality as estimated by dye binding capacity was considerably affected. PMID- 2247436 TI - Proteins and amino acids of some local varieties of rice seeds (Oryza Sativa L.). AB - Proteins and amino acids in four local rice (Oryza Sativa L.) varieties were identified. Albumin and globulin were extracted from rice seeds, and the major promoters of these proteins were investigated by polyacrylamide gel electrophoresis to show their patterns. Amino acid composition of the rice seed were determined quantitatively and qualitatively, and classified according to their acidic, basic and uncharged polar groups. Essential amino acids for each variety were determined, and the hydrophobicity index value of Amber 33 was (0.6078), Mishkhab 1 (0.63372), Hybrid 2 (0.6523) and Hwazawi (0.7411). PMID- 2247435 TI - Influence of sulfur-amino acid content variation in plant vs animal protein on serum and tissue lipids in rats. AB - The objective of the study was to determine the effects of methionine and cysteine supplementation of soy protein isolate and casein on serum and tissue lipid levels in rats. Sixty male, weanling, Wistar-Kyoto rats were fed two sources of protein (casein or soy protein isolate) and three variations of sulfur amino acid supplementation (none, methionine, or cysteine). At this level of protein intake (10% by weight), rats fed soy-based diets had similar serum lipid concentrations than rats fed casein-based diets. Choline was not added to the diet in order to be able to assess independent influences of methionine and cysteine on lipid metabolism. Overall, serum lipid values were greater in rats fed proteins supplemented with methionine while the addition of cysteine produced lower lipid levels. Liver lipid concentrations were increased tremendously upon cysteine supplementation of soy protein isolate. Protein quality, as determined by protein efficiency ratio, was improved by supplementation of either sulfur amino acid; however, methionine had the greatest effect. Results indicate that the sulfur-amino acids influence lipid metabolism in the absence of dietary choline. The mechanism by which this occurs is not known. PMID- 2247437 TI - Tat-responsive region RNA of human immunodeficiency virus 1 can prevent activation of the double-stranded-RNA-activated protein kinase. AB - Transcription from the human immunodeficiency virus type 1 promoter gives rise to short cytoplasmic transcripts of approximately 60 nucleotides as well as to longer mRNAs. These RNAs contain the Tat-responsive region sequence, which is capable of assuming a stem-loop structure and has been implicated in the regulation of both transcription and translation. It has been reported that Tat responsive region RNA inhibits translation in vitro through activation of an interferon-induced protein kinase, the double-stranded-RNA-activated inhibitor, which phosphorylates eukaryotic initiation factor 2. We show that the activation property is due to double-stranded RNA that often contaminates RNA synthesized in vitro using bacteriophage RNA polymerases. After purification, high concentrations of Tat-responsive region RNA inhibit the activation of double stranded RNA-activated inhibitor, suggesting that it may serve to protect human immunodeficiency virus type 1 infection from a cellular defense mechanism. PMID- 2247438 TI - Two genes encode factors with NF-kappa B- and H2TF1-like DNA-binding properties. AB - NF-kappa B and H2TF1 are transcription factors that bind to related DNA sequence motifs. NF-kappa B is a constitutive factor in mature B lymphocytes and is inducible in immature B cells and nonlymphoid cells. H2TF1 is a constitutive ubiquitous transcription factor that activates expression of major histocompatibility complex class I genes. We report here the isolation of two zinc finger genes. One, named MBP-2 (major histocompatibility complex-binding protein 2), encodes a factor that has DNA-binding properties similar, if not identical, to the H2TF1 transcription factor. The second, named KBP-1 (kappa enhancer binding protein 1), encodes a factor that is similar to, but distinct from, NF-kappa B in its DNA-binding properties and methylation interference pattern, suggesting that at least two proteins can bind to the immunoglobulin kappa gene enhancer. PMID- 2247440 TI - Mutations in genetic variants of human serum albumin found in Italy. AB - A long-term electrophoretic survey of genetic variants of serum albumin has identified an alloalbumin in 589 unrelated individuals in Italy. The alloalbumins were classified electrophoretically into 17 types. The number of unrelated carriers for each type varied from 1 for several variants reported here to 103 for albumin B. The structural change in 8 of these types has previously been determined, and the amino acid substitutions in 3 additional types are reported here. Albumin Varese has a substitution, -2 arginine to histidine (-2 Arg--- His), the same as that reported for proalbumin Lille; albumin Torino has the substitution 60 Glu----Lys; and albumin Vibo Valentia has the substitution 82 Glu ---Lys. The ability to distinguish so many alloalbumin types by electrophoresis at several pH values indicates that similar substitutions at different sites produce variants with different electrophoretic mobilities. Except for chain terminations in two Italian variants, all the mutations thus far determined for alloalbumins are attributable to a single-base change in the structural gene, and there is a preponderance of transitions and purine mutations. Seven alloalbumins for which the structural change has been established have been ascertained only in Italy. Several of these are clustered in specific geographic regions of Italy, which suggests an origin through a founder individual. Other variants that occur worldwide are nonetheless clustered in geographic regions within Italy. In these cases an independent mutation probably occurred at a hypermutable site such as a CpG dinucleotide. PMID- 2247439 TI - Leucine-rich repeats and carboxyl terminus are required for interaction of yeast adenylate cyclase with RAS proteins. AB - A Saccharomyces cerevisiae gene encoding adenylate cyclase has been analyzed by deletion and insertion mutagenesis to localize regions required for activation by the Sa. cerevisiae RAS2 protein. The NH2-terminal 657 amino acids were found to be dispensable for the activation. However, almost all 2-amino acid insertions in the middle 600 residues comprising leucine-rich repeats and deletions in the COOH terminal 66 residues completely abolished activation by the RAS2 protein, whereas insertion mutations in the other regions generally had no effect. Chimeric adenylate cyclases were constructed by swapping the upstream and downstream portions surrounding the catalytic domains between the Sa. cerevisiae and Schizosaccharomyces pombe adenylate cyclases and examined for activation by the RAS2 protein. We found that the fusion containing both the NH2-terminal 1600 residues and the COOH-terminal 66 residues of the Sa. cerevisiae cyclase rendered the catalytic domain of the Sc. pombe cyclase, which otherwise did not respond to RAS proteins, activatable by the RAS2 protein. Thus the leucine-rich repeats and the COOH terminus of the Sa. cerevisiae adenylate cyclase appear to be required for interaction with RAS proteins. PMID- 2247441 TI - Filler DNA is associated with spontaneous deletions in maize. AB - We have determined the structure of five spontaneous deletions within the maize waxy (Wx) gene. Of these, four were found in spontaneous wx mutants (wx-B, wx-B1, wx-B6, wx-C4) and include exon sequences; the fifth is restricted to an intron and represents a restriction fragment length polymorphism of a nonmutant allele (Wx-W23). The deletions, which range in size from 60 to 980 base pairs (bp), cluster in a G+C-rich region of approximately 1000 bp that is capable of forming stable secondary structures. Most striking is our finding that all of the alleles have DNA insertions (filler DNA) of 1-131 bp between the deletion endpoints. For three of the five deletions, the filler DNA and sequences at the deletion termini appear to be derived from sequences near one deletion endpoint. A previously reported spontaneous deletion of the maize bronze gene (bz-R) also contains filler DNA. The association of filler DNA with maize deletion endpoints contrasts dramatically with the rarity of similar events in animal germ-line and bacterial mutations. PMID- 2247442 TI - Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. AB - Although hematopoiesis is known to originate in a population of very primitive cells with both lymphopoietic and myelopoietic potential, a procedure for enumerating such cells has to date not been available. We now describe a quantitative assay for long-term repopulating stem cells with the potential for reconstituting all hematopoietic lineages. This assay has two key features. The first is the use of competitive repopulation conditions that ensure not only the detection of a very primitive class of hematopoietic stem cells but also the survival of lethally irradiated mice transplanted with very low numbers of such cells. The second is the use of a limiting-dilution experimental design to allow stem cell quantitation. The assay involves transplanting limiting numbers of male "test" cells into lethally irradiated syngeneic female recipients together with 1 2 x 10(5) syngeneic female marrow cells whose long-term repopulating ability has been compromised by two previous cycles of marrow transplantation. The proportion of assay recipients whose regenerated hematopoietic tissues are determined to contain greater than or equal to 5% cells of test cell origin (male) greater than or equal to 5 weeks later is then used to calculate the frequency of competitive repopulating units (CRU) in the original male test cell suspension (based on Poisson statistics). Investigation of this assay system has shown that all three potential sources of stem cells (test cells, compromised cells, and the host) can under appropriate circumstances contribute to long-term hematopoietic regeneration, thus establishing both the competitive pressure of hematopoietic stem cells in the cotransplanted compromised population and in the host, and the need to use genetic markers to track the specific contribution of the injected test cells. Analysis of the frequency of CRU in test marrow suspensions that varied widely in their CRU content gave similar values when endpoints of either 5 or 10 weeks posttransplantation were used and when either recipient marrow or thymus was used to identify progeny populations. In addition, repopulation of marrow and thymus was found to be associated in most mice injected with limiting numbers of test cells. These findings are consistent with the conclusion that the assay is highly selective for a very primitive, totipotent, reconstituting hematopoietic stem cell and should therefore be particularly useful in future gene therapy-oriented research as well as for more basic studies of hematopoietic stem cell regulation and differentiation. PMID- 2247443 TI - Effects on adaptedness of variations in ribosomal DNA copy number in populations of wild barley (Hordeum vulgare ssp. spontaneum). AB - Twenty alleles, 12 at Mendelian locus Rrn1 and 8 at locus Rrn2, control rRNA genes [ribosomal DNA (rDNA)] variability in barley. These alleles differ strikingly in their effects on adaptedness. In the present study, we determined variation in the copy number of 101 accessions of wild barley plants from 10 ecologically diverse sites in Israel and examined relationships between rDNA copy number and adaptedness. The average multiplicity of rDNA per haploid genome was 1881 copies and the average numbers of copies for Rrn1 and Rrn2 were 962 and 917, respectively. The total number of copies as well as the number of copies for Rrn1 and Rrn2 varied widely from plant to plant within sites and also from site to site. The predominant allele of Rrn2 had somewhat more copies on the average than the other alleles of this locus but differences between the predominant allele and other alleles of Rrn1 were not statistically significant. Overall, the results indicated that differing amounts of rDNA resulting from variations in copy number and/or number of subrepeats in the intergenic spacer region were not closely associated with adaptedness. This suggests that the high adaptedness of a few specific alleles results in large part from adaptatively favorable nucleotide sequences in the transcription units and/or the intergenic spacer regions of the favored alleles--i.e., that adaptedness in barley depends on the quality more than on the quantity of rDNA present. PMID- 2247444 TI - Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. AB - The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV infected cells for the therapy of HIV-mediated pathogenesis. PMID- 2247445 TI - Analysis of gene families encoding acidic and basic beta-1,3-glucanases of tobacco. AB - Healthy tobacco plants accumulate beta-1,3-glucanases (glucan endo-1,3-beta glucosidase; EC 3.2.1.39) in their roots and in specific parts of the flowers. After infection with tobacco mosaic virus, acidic and basic beta-1,3-glucanases are induced in the inoculated and virus-free leaves of the plant. An analysis of cDNA clones demonstrated that at least five genes for acidic beta-1,3-glucanases are induced after tobacco mosaic virus infection. Southern blot analysis indicated that the tobacco genome contains approximately eight genes for acidic beta-1,3-glucanases and a smaller number of genes encoding basic beta-1,3 glucanases. Genes from both gene families were cloned and sequenced. The basic isozymes contain a C-terminal extension that is cleaved off during their targeting to the vacuoles. This extension is absent in the acidic isozymes, which accumulate extracellularly. Northern blot hybridization showed that genes encoding acidic and basic beta-1,3-glucanases are strongly induced after tobacco mosaic virus infection or salicylate treatment of tobacco. The cloning of these genes is a first step toward the identification of regulatory elements involved in their coordinate induction. PMID- 2247446 TI - Developmentally regulated expression of an exon containing a stop codon in the gene for glutamic acid decarboxylase. AB - In the adult rat brain, the gene for glutamic acid decarboxylase (GAD; L glutamate 1-carboxy-lyase, EC 4.1.1.15) is expressed predominantly as a 3.7 kilobase transcript. Earlier data showed that embryonic brain expresses an RNA transcript distinct from the adult form; however, the exact structure of this form was not elucidated. Here, transcripts expressed in the embryonic but not the adult brain were cloned and analyzed. These transcripts include an exon not expressed in the adult inserted into coding sequence. The embryonic exon contains a stop codon that is in-frame with the coding sequence. The exon is found in genomic DNA within the GAD gene where it is flanked by introns with conventional splice sites. On the basis of these structural data, we propose the hypothesis that, early in brain development, transcripts encoding a truncated form of GAD are expressed. The deduced protein cannot function as a decarboxylase because the stop codon in the embryonic exon occurs upstream of the binding site for pyridoxal phosphate, an essential cofactor. Thus, alternative splicing plays a crucial role in the pathway leading to the development of functional GABAergic neurons. The central nervous system-derived cell lines B65 and C6 express a mixture of the adult and embryonic forms of GAD mRNA. They therefore are useful clonal models of central nervous system cells in the early phases of differentiation. PMID- 2247447 TI - Mutations in the DET1 gene affect cell-type-specific expression of light regulated genes and chloroplast development in Arabidopsis. AB - When grown in the absence of light, the det1 mutant of Arabidopsis thaliana develops characteristics of a light-grown plant by morphological, cellular, and molecular criteria. Here, we show that recessive mutations at the DET1 locus also result in cell-type inappropriate accumulation of RNAs for light-regulated nuclear and chloroplast genes. det1 root plastids are differentiated into chloroplasts and are present in very high numbers in root cortex cells in contrast to the few starch-containing amyloplasts normally found in Arabidopsis roots. To assay the effect of the det1 mutation on the expression of photoregulated promoters, we used fusion constructs to stably transform wild-type and det1 mutants. We show that the three red-light-regulated chlorophyll a/b binding protein promoters are inappropriately expressed in the roots of det1 seedlings and the blue-light-controlled anthocyanin biosynthetic gene, chalcone synthase, is expressed ectopically in leaf mesophyll cells. These results, together with out previous findings, suggest that the DET1 gene product is a negatively acting regulatory molecule that is used in common by the light stimulus transduction pathway and by temporal or spatial regulatory signals in plants. PMID- 2247448 TI - Sustained vortex-like waves in normal isolated ventricular muscle. AB - Sustained reentrant excitation may be initiated in small (20 x 20 x less than 0.6 mm) preparations of normal ventricular muscle. A single appropriately timed premature electrical stimulus applied perpendicularly to the wake of a propagating quasiplanar wavefront gives rise to circulation of self-sustaining excitation waves, which pivot at high frequency (5-7 Hz) around a relatively small "phaseless" region. Such a region develops only very low amplitude depolarizations. Once initiated, most episodes of reentrant activity last indefinitely but can be interrupted by the application of an appropriately timed electrical stimulus. The entire course of the electrical activity is visualized with high temporal and spatial resolution, as well as high signal-to-noise ratio, using voltage-sensitive dyes and optical mapping. Two- and three-dimensional graphics of the fluorescence changes recorded by a 10 x 10 photodiode array from a surface of 12 x 12 mm provide sequential images (every msec) of voltage distribution during a reentrant vortex. The results suggest that two-dimensional vortex-like reentry in cardiac muscle is analogous to spiral waves in other biological and chemical excitable media. PMID- 2247450 TI - Biosynthesis of vitamin B12: structure of precorrin-6x octamethyl ester. AB - 13C-labeled precorrin-6x is biosynthesized by cell-free protein preparations from Pseudomonas denitrificans in separate experiments using delta-amino[5 13C]levulinic acid and the corresponding delta-amino[4-13C]- and delta-amino[3 13C]levulinic acid-labeled forms in conjunction with S-[methyl 13C]adenosylmethionine for the latter two experiments. These labeled precorrin-6x samples, as their octamethyl esters, are studied by a range of NMR techniques. In addition, nuclear Overhauser effect difference measurements are made on unlabeled precorrin-6x ester to determine connectivities. The structure 6a so established for precorrin-6x ester (i) confirms the results reported in the preceding paper that precorrin-6x has a ring-contracted macrocycle, still carries the C-12 acetate residue, and stands at the oxidation level of a dehydrocorrin; (ii) reveals the unexpected methylation at C-11 not C-12, leading to a structure with separated chromophores; and (iii) implies that methyl migration from C-11 to C-12 occurs when precorrin-6x is converted into hydrogenobyrinic acid. Proposals for the biosynthesis of the corrin macrocycle of hydrogenobyrinic acid and vitamin B12 are made. PMID- 2247449 TI - Biosynthesis of vitamin B12: isolation of precorrin-6x, a metal-free precursor of the corrin macrocycle retaining five S-adenosylmethionine-derived peripheral methyl groups. AB - delta-Aminolevulinic acid and trimethylisobacteriochlorin are converted by cell free protein preparations from Pseudomonas denitrificans into a metal-free pigment, precorrin-6x. This pigment, which accumulates when the cell-free system lacks NADPH, can be enzymically converted in high yield (greater than 50%) into hydrogenobyrinic acid by the complete enzyme preparation. Double-labeling experiments establish that precorrin-6x carries five C-methyl groups, which appear at C-1, C-2, C-7, C-12 alpha, and C-17 of the hydrogenobyrinic acid formed enzymically from precorrin-6x. This precursor of the corrin macrocycle is at the dehydrocorrin level of oxidation, has undergone ring contraction and extrusion of C-20, but still carries the acetic acid side chain at C-12. It is demonstrated that the conversion of precorrin-6x into hydrogenobyrinic acid specifically requires an NADPH-dependent reduction step. PMID- 2247451 TI - X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor. AB - The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe; the Ki is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-A resolution by using restrained least squares with rms deviations in bond lengths of 0.02 A and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365. PMID- 2247452 TI - Cytokinin-induced mRNAs in cultured soybean cells. AB - We have isolated 20 cDNA clones for which the corresponding mRNAs accumulate 2- to 20-fold within 4 hr of cytokinin addition to cytokinin-starved soybean suspension cultures. These changes in mRNA levels precede the greening and cell growth induced by cytokinin in this system. Treatment with cycloheximide before cytokinin addition enhances the accumulation of these messages. In addition, the abundance of these mRNAs is influenced by auxin. We demonstrate that the mRNAs corresponding to the cDNAs in this collection display a variety of patterns of accumulation in the tissues of an intact plant. We also show that different cytokinins induce similar increases in message levels. However, analogs of cytokinin that are much less active in bioassays induce lower levels of message accumulation. Sequence analyses indicate that two of the cDNAs correspond to ribosomal protein genes. The remaining cDNAs are likely to represent previously undiscovered genes that function early in the initiation of plant cell growth and/or chloroplast development. PMID- 2247454 TI - Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues. AB - Masking protein (MP), which neutralizes the activity of transforming growth factor type beta 1 (TGF-beta 1), is composed of a dimeric N-terminal part of a TGF-beta 1 precursor of Mr 39,000 and an unknown large subunit of Mr 105,000 120,000. The deduced primary structure of the MP large subunit was elucidated by determining the nucleotide sequence of its cDNA. The cDNA encodes a prepro precursor of 1712 amino acid residues with a calculated Mr of 186,596. The mature large subunit seems to be derived proteolytically from a prepro-precursor and the calculated Mr is 91,606. The precursor has seven N-linked glycosylation sites and an unusual structure containing 18 epidermal growth factor-like domains and four cysteine-rich internal repeats. The large subunit mRNA is synthesized in parallel with the expression of TGF-beta 1 mRNA in various rat tissues. PMID- 2247453 TI - Interindividual concordance of methylation profiles in human genes for tumor necrosis factors alpha and beta. AB - The DNA in mammalian genomes is characterized by complex patterns of DNA methylation that reflect the states of all genetic activities of that genome. The modified nucleotide 5-methyldeoxycytidine (5mdC) can affect the interactions of specific proteins with DNA sequence motifs. The most extensively studied effect of sequence-specific methylations is that of the long-term silencing of eukaryotic (mammalian) promoters. We have initiated studies on the methylation status of parts of the human genome to view patterns of DNA methylation as indicators for genetic activities. In this report, analyses using both restriction enzyme--Southern blotting and the very precise genomic sequencing technique have been done. The genes for tumor necrosis factors (TNF) alpha and beta--in particular, their 5'-upstream and promoter regions--have been investigated in DNA isolated from human lymphocytes, granulocytes, and sperm. The results are characterized by a remarkable interindividual concordance of DNA methylation in specific human cell types. The patterns are identical in the DNA from one cell type for different individuals even of different genetic origins but different in the DNA from different cell types. As an example, in the DNA from human granulocytes of 15 different individuals (ages 20-48 yr, both sexes), 5mdC residues have been localized by the genomic sequencing technique in three identical sequence positions in the 5'-upstream region and in one downstream position of the gene encoding TNF-alpha. The promoter of this gene is free of 5mdC, and TNF-alpha is expressed in human granulocytes. The TNF-beta promoter is methylated in granulocytes from 9 different individuals, and TNF-beta is not expressed. In human lymphocytes, the main source of TNF-beta, the TNF-beta promoter is free of 5mdC residues. All 5'-CG-3' sites studied in the TNF-alpha and -beta genes are methylated in DNA from human sperm. In human cell lines HL 60, Jurkat, and RPMI 1788, the extent of DNA methylation in TNF-alpha and -beta genes has also been studied. PMID- 2247455 TI - Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama. AB - Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy. However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection. Recent studies indicate that a high percentage of certain groups of i.v. drug users and blood donors are infected with HTLV-II. Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama. To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians. The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions. A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen capture and immunoblot assays, as well as mature HTLV particles. The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus. PMID- 2247456 TI - Nucleotide sequence and expression of a deep-sea ribulose-1,5-bisphosphate carboxylase gene cloned from a chemoautotrophic bacterial endosymbiont. AB - The gene coding for ribulose-1,5-bisphosphate carboxylase [RuBisCO; 3-phospho-D glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] was cloned from a sulfur oxidizing chemoautotrophic bacterium that resides as an endosymbiont within the gill tissues of Alvinoconcha hessleri, a gastropod inhabiting deep-sea hydrothermal vents. Nucleotide sequence analysis of the cloned fragment demonstrated that the genes encoding the large (RbcL) and small (RbcS) subunits of the symbiont RuBisCO were organized similarly to the RuBisCO operons of free living photo- and chemoautotrophic prokaryotes. The symbiont rbcL gene shared the highest degree of nucleotide sequence identity with the cyanobacterium Anabaena (69%) while the rbcS nucleotide sequence shared 61% identity with that of the green alga Chlamydomonas reinhardtii. Comparison with a 153-nucleotide partial rbcL sequence from a symbiont of the bivalve Solemya reidi indicated that the two symbiont sequences shared 85% sequence identity at the nucleotide level and 93% at the amino acid level, suggesting a relatively recent common origin. Escherichia coli transformed with a plasmid carrying the RuBisCO operon of the gastropod symbiont in the proper orientation for transcription from the plasmid lac promoter expressed catalytically active RuBisCO. The presence of enzyme activity suggests the proper assembly of the subunits of this deep-sea RuBisCO into the holoenzyme. PMID- 2247457 TI - Identification of amino acids inserted during suppression of UAA and UGA termination codons at the gag-pol junction of Moloney murine leukemia virus. AB - Expression of the murine leukemia virus pol gene occurs by translational readthrough of an in-frame UAG codon between the gag and pol coding regions. In a previous study, we mutated the UAG codon to UAA or UGA and demonstrated that both of these termination codons could be suppressed in reticulocyte lysates and in infected cells with the same efficiency as UAG. We now report the identity of the amino acids inserted in vitro in response to UAA and UGA in fusion products containing the gag-pol junction region. The results show that UAA, like UAG, directs the incorporation of glutamine, whereas UGA directs the incorporation of three amino acids, arginine, cysteine, and tryptophan. To our knowledge, this is the first report indicating misreading of UAA as glutamine and UGA as arginine and cysteine in higher eukaryotes. Interestingly, although our protein synthesis system presumably contains other known UAG and UGA suppressors, these tRNAs did not suppress the termination codons in our experiments. Thus, it seems possible that the sequence surrounding the gag-pol junction not only promotes suppression but also helps determine which tRNAs function in suppression. PMID- 2247458 TI - Domain communication in the dynamical structure of human immunodeficiency virus 1 protease. AB - A dynamical model for the structure of the human immunodeficiency virus 1 (HIV-1) protease dimer in aqueous solution has been developed on the basis of molecular dynamics simulation. The model provides an accurate account of the crystal geometry and also a prediction of the structural reorganization expected to occur in the protein in aqueous solution compared to the crystalline environment. Analysis of the results by means of dynamical cross-correlation coefficients for atomic displacements indicates that domain-domain communication is present in the protein in the form of a molecular "cantilever" and is likely to be involved in enzyme function at the molecular level. The dynamical structure also suggests information that may ultimately be useful in understanding and further development of specific inhibitors of HIV-1 protease. PMID- 2247459 TI - Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis. AB - Human plasma contains a factor Xa-dependent inhibitor of tissue factor/factor VIIa complex termed lipoprotein-associated coagulation inhibitor (LACI). The present study examines the site(s) of LACI synthesis. In this study, cultured hepatocytes isolated from normal human liver were found to be essentially negative in LACI mRNA as revealed by Northern blot analysis using a full-length LACI cDNA as probe. The conditioned media from these cultures were also essentially negative for LACI activity. Similarly, poly(A)+ RNA obtained from normal human liver did not contain detectable LACI mRNA. In contrast, cultured human umbilical vein endothelial cells and human lung tissue (rich in endothelium) both contained abundant amounts of LACI mRNA. Moreover, erythrocyte lysates and culture media from normal monocytes, lymphocytes, or neutrophils did not contain measurable LACI activity; these cells were also negative for LACI mRNA. Platelets, however, contained LACI activity. The likely source of platelet LACI is the megakaryocyte cell since a megakaryocyte cell line (MEG-01) was found to contain LACI mRNA and to secrete small amounts of LACI activity. Additionally, human vascular smooth muscle cells and lung fibroblasts were also found to synthesize only small amounts of LACI. From these observations, we conclude that normal liver does not synthesize LACI and that endothelium is the principal source of plasma LACI. The undegraded LACI synthesized by endothelial cells had a molecular weight of approximately 41,000. PMID- 2247460 TI - Molecular cloning of complementary DNAs encoding two cationic peroxidases from cultivated peanut cells. AB - We have isolated, cloned, and characterized two cDNAs corresponding to the mRNAs for cationic peroxidases synthesized by cultured peanut cells. The first clone was obtained from a phage lambda gt11 library screened with antibodies directed against the major secreted isozyme. Its predicted amino acid sequence, deduced from the 1228-base-pair (bp) cDNA, revealed a 22-amino acid signal peptide and a 294-amino acid mature protein (Mr, 31,228). The second clone was isolated from a lambda gt10 library screened with oligonucleotides corresponding to the regions for acid/base catalysis and the fifth ligand of heme. This cDNA (1344 bp) encodes a protein (330 amino acids) with a mature peptide of 307 residues (Mr, 32,954). The two peanut peroxidases are 46% homologous. The estimated gene copy numbers of these peroxidases might be close to 1 or 2 per haploid genome. A comparison of the amino acid sequence of these peanut peroxidases with other known isozymes shows two already known regions of homology (the region for acid/base catalysis and the fifth ligand of heme). Moreover, some new characteristics appeared such as a glycosylation site identical in five of the seven isozymes, a putative antigenic determinant common to all the isozymes, and a region of the highest homology. A secondary structure prediction showed that it corresponds to a 16 amino acid helix linked to the next one by a long stretch of beta strands and coils and might represent a critical structural element. PMID- 2247462 TI - Systemic movement of an RNA plant virus determined by a point substitution in a 5' leader sequence. AB - The ability of viruses to move through infected plants is an important determinant of host range and pathogenicity. We have investigated the genetic basis for the inability of the Type strain of barley stripe mosaic hordeivirus to undergo long-range systemic movement in the tobacco Nicotiana benthamiana. We show that, in this model system, a short open reading frame in the 5' leader of the smallest viral genomic RNA prevents long-range vascular movement. As predicted by the ribosome scanning model, the leader open reading frame decreases the efficiency with which the 5'-proximal gene is translated in vitro. Thus, systemic pathogenicity in this system may be determined by the efficiency of translation of a viral gene in vivo and is not determined by the primary sequence of the encoded protein. PMID- 2247461 TI - A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni. AB - We present evidence that a subset of mRNAs in the human parasitic trematode Schistosoma mansoni contain an identical 36-nucleotide spliced leader (SL) sequence at their 5' termini. The SL is derived from a 90-nucleotide nonpolyadenylylated RNA (SL RNA), presumably by trans-splicing. Neither the SL nor the SL RNA share significant sequence identity with previously described trans-spliced leaders and SL RNAs in trypanosomatid protozoans or nematodes. However, several features, such as predicted secondary structure, trimethylguanosine cap, and potential Sm binding site, suggest similarities among SL RNAs in widely divergent organisms. Our evidence also indicates that the exon 3 acceptor site of the 3-hydroxy-3-methylglutaryl-CoA reductase gene can be spliced either to the SL by trans-splicing or to an upstream exon, 2, by cis splicing. The presence of a SL sequence in S. mansoni, a member of the phylum Platyhelminthes, suggests that transplicing may be a common feature of other lower invertebrates. PMID- 2247463 TI - Bathoiodopsin, a primary intermediate of iodopsin at physiological temperature. AB - Measurement of the primary photochemical reaction of iodopsin, a chicken red sensitive cone visual pigment, was carried out at room temperature by using picosecond (ps) laser photolysis. Excitation of iodopsin with a ps green pulse (pulse width, 21 ps) caused the instantaneous formation of a bathochromic product, which was stable on a ps time scale. This product may correspond to "bathoiodopsin," which was detected by low-temperature spectrophotometry. Although bathoiodopsin produced at the temperature of liquid nitrogen or helium reverted to the original pigment (iodopsin) on warming (above -170 degrees C), the bathoiodopsin produced at physiological temperature decayed to all-trans retinal and R-photopsin (the protein moiety of iodopsin) presumably through several intermediates. The absorption maximum of bathoiodopsin at room temperature was at 625 nm, a wave-length slightly shorter than that measured at low temperature (lambda max, 640 nm). The extinction coefficient of bathoiodopsin at room temperature was lower than that at low temperature and close to that of the original iodopsin at room temperature. PMID- 2247464 TI - Putative tyrosine kinases expressed in K-562 human leukemia cells. AB - Tyrosine phosphorylation is important in the transmission of growth and differentiation signals; known tyrosine kinases include several oncoproteins and growth factor receptors. Interestingly, some differentiated cell types, such as erythrocytes and platelets contain high amounts of phosphotyrosine. We analyzed tyrosine kinases expressed in the K-562 chronic myelogenous leukemia cell line, which has a bipotential erythroid and megakaryoblastoid differentiation capacity. Analysis of 359 polymerase chain reaction-amplified cDNA clones led to the identification of 14 different tyrosine kinase-related sequences (JTK1-14). Two of the clones (JTK2 and JTK4) represent unusual members of the fibroblast growth factor receptor gene family, and the clones JTK5, JTK11, and JTK14 may also belong to the family of receptor tyrosine kinases but lack a close relationship to any known tyrosine kinase. Each of these different genes has its own characteristic expression pattern in K-562 cells and several other human tumor cell lines. In addition, the JTK11 and JTK14 mRNAs are induced during the megakaryoblastoid differentiation of K-562 cells. These tyrosine kinases may have a role in the differentiation of megakaryoblasts or in the physiology of platelets. PMID- 2247465 TI - Differential intron loss and endosymbiotic transfer of chloroplast glyceraldehyde 3-phosphate dehydrogenase genes to the nucleus. AB - Chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is composed of two different subunits, GAPA and GAPB, which are encoded in the nucleus by two related genes of eubacterial origin. In the present work the genes encoding chloroplast GAPA and GAPB from pea have been cloned and sequenced. The gene for GAPB is split by eight introns. Two introns interrupt the region encoding the transit peptide and six are found within the region encoding the mature subunit, four of which are in identical or similar positions relative to genes for cytosolic GAPDH of eukaryotic organisms. As opposed to this, the gene encoding pea GAPA has only two introns in the region encoding the mature subunit. These findings strongly support the "intron early" hypothesis and suggest that the low number of introns in the gene for chloroplast GAPA is due to differential loss of introns during the streamlining period of the chloroplast genome following the GAPB/GAPA separation. We deduce from this that eubacteria and chloroplasts contained GT-AG introns until relatively recently and that the duplication event leading to the genes encoding GAPB and GAPA and their respective transit peptides occurred in the chloroplast progenitor prior to the successive transfer and functional reintegration of these genes into the nuclear environment. These conclusions imply that GAPA/GAPB transit peptides are of eubacterial origin. PMID- 2247466 TI - Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay. AB - DNA diagnostics, the detection of specific DNA sequences, will play an increasingly important role in medicine as the molecular basis of human disease is defined. Here, we demonstrate an automated, nonisotopic strategy for DNA diagnostics using amplification of target DNA segments by the polymerase chain reaction (PCR) and the discrimination of allelic sequence variants by a colorimetric oligonucleotide ligation assay (OLA). We have applied the automated PCR/OLA procedure to diagnosis of common genetic diseases, such as sickle cell anemia and cystic fibrosis (delta F508 mutation), and to genetic linkage mapping of gene segments in the human T-cell receptor beta-chain locus. The automated PCR/OLA strategy provides a rapid system for diagnosis of genetic, malignant, and infectious diseases as well as a powerful approach to genetic linkage mapping of chromosomes and forensic DNA typing. PMID- 2247467 TI - Lovastatin decreases coenzyme Q levels in rats. AB - Lovastatin is used for the treatment of hypercholesterolemia. It functions by inhibiting the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), that is required for the conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid. Since biosynthesis of both cholesterol and coenzyme Q (CoQ) requires mevalonic acid as a precursor, it was considered that lovastatin therapy would also result in a lowering of cellular CoQ levels. This study was conducted to determine whether lovastatin treatment does decrease CoQ levels and whether such decreases can be prevented by CoQ supplementation. Forty-five adult male Holtzman rats were randomly assigned to one of three treatment groups. Controls were fed ground laboratory rat chow ad libitum. The other two groups were fed ground laboratory rat chow containing 400 mg of lovastatin per kg of diet ad libitum. One of the lovastatin-fed groups received CoQ10 (15 mg per kg of body weight) daily via stomach intubation. After 4 weeks, samples of heart, liver, and blood were analyzed for CoQ concentrations. Results indicated that CoQ concentrations in all tissues analyzed were decreased in lovastatin-treated rats. Lovastatin-treated animals that were supplemented with CoQ10 had blood, heart, and liver CoQ10 concentrations that approximated or exceeded those of control animals. It is concluded that lovastatin does indeed lower tissue concentrations of CoQ and that a return to normal can be achieved by supplementation with CoQ. PMID- 2247468 TI - Lovastatin decreases coenzyme Q levels in humans. AB - Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10. PMID- 2247469 TI - Oscillatory activity of single units in a somatosensory cortex of an awake monkey and their possible role in texture analysis. AB - Neuronal activity was extracellularly recorded in the cortex of an awake monkey (Macaca fascicularis). Single units displaying oscillatory firing patterns were found in the upper bank of the lateral sulcus in a region where most of the neurons responded to somatosensory stimuli. The spectral energies of the oscillating activity were distributed in a trimodal fashion--0-15, 15-50, and 80 250 Hz--with the most common frequencies around 30 Hz. The oscillatory activity was not affected by anesthesia, but it was often reduced by tactile stimulation or self-initiated movements. Analysis of the spike trains suggests that the majority of oscillatory activity was intrinsically generated by the neurons. A neural model of texture analysis is offered based on a corticothalamic phase locked loop. The newly identified oscillators play a key role in this model. The relevance of the model to physiological, anatomical, and psychophysical data, as well as testable predictions, are discussed. PMID- 2247470 TI - Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism. AB - In the retinae of many vertebrates, there are classes of horizontal cell that probably utilize gamma-aminobutyric acid (GABA) as a neurotransmitter. As with other amino acid transmitter agents, the postsynaptic action of GABA is thought to be terminated by uptake into neurons and glia surrounding the release site. The present study examined whether an uptake system for GABA could be detected in isolated skate horizontal cells by means of electrophysiological methods. Pressure ejection of GABA onto voltage-clamped horizontal cells produced an inward current that showed no sign of desensitization regardless of the GABA concentration. The dose-response relationship followed simple Michaelis-Menten kinetics, with a half-maximal response elicited at approximately 110 microM. Nipecotic acid produced a similar current and reduced the responses to GABA when introduced in the bath solution prior to the GABA pulse. On the other hand, application of 500 microM muscimol or 1 mM baclofen, GABAA and GABAB receptor agonists, respectively, were completely without effect. The GABA-induced current was not blocked by superfusion with 500 microM bicuculline, 500 microM picrotoxin, or 500 microM phaclofen. However, the responses to GABA were abolished when the cells were superfused in Ringer's solution in which choline or lithium had been substituted for sodium, and were reduced when the extracellular chloride concentration was decreased from 266 mM to 16 mM. Current-voltage data showed a maximal response to GABA when the cells were held at or below their resting potential. At more depolarized levels, the inward current became progressively smaller until, near +50 mV, it could no longer be detected; over the range tested (-90 to +50 mV), the response never reversed into an outward current. These findings suggest that the GABA-induced currents in skate horizontal cells are mediated by an electrogenic uptake mechanism. PMID- 2247471 TI - Expression of the archaebacterial bacterio-opsin gene with and without signal sequences in Escherichia coli: the expressed proteins are located in the membrane but bind retinal poorly. AB - In a further effort to obtain functional expression of the bacterio-opsin gene (bop) in Escherichia coli, the bop gene with E. coli signal sequences as well as the bop gene with the native presequence were expressed in E. coli. The location of the expressed products in the E. coli cell and their processing and folding to a structure that binds retinal as in Halobacterium halobium were investigated. All the expressed proteins were in the membrane. The proteins were largely unprocessed, and they were distributed between the outer and the inner membrane. The processed fractions, which were minor, were exclusively in the inner membrane. The processed proteins bound exogenously added all-trans-retinal but only partially, indicating that these proteins were present in at least two folded states. PMID- 2247472 TI - Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes. AB - Antisera that recognize the alpha 6 and beta 4 subunits of integrins were found by immunoelectron microscopy to localize to hemidesmosomes in the basal cells of mouse corneal epithelium. Immunoprecipitation experiments using extracts of metabolically labeled corneal epithelial cells indicate that the primary alpha 6 subunit-containing integrin heterodimer present is alpha 6 beta 4 and not alpha 6 beta 1. Here we extend previous studies to report that by immunofluorescence microscopy the alpha 6 integrin subunit colocalizes with bullous pemphigoid antigen and type VII collagen in newly forming hemidesmosomes in the developing 17-day fetal rabbit eye. Neither the composition of the anchoring filaments, which span the region between the hemidesmosomal plaque and the lamina densa of basement membrane where the globular domain of type VII collagen is located, nor the extracellular ligand of alpha 6 beta 4 is known. Once anchoring filament proteins are identified, it will be of interest to determine whether any bind to alpha 6 beta 4. PMID- 2247473 TI - Acylation-stimulatory activity in hyperapobetalipoproteinemic fibroblasts: enhanced cholesterol esterification with another serum basic protein, BP II. AB - Cultured fibroblasts from patients with familial hyperapobetalipoproteinemia (hyperapoB) were used to determine if a defect in lipid metabolism was present. Three basic proteins (BP I, BP II, and BP III) were isolated from normal human serum by preparative isoelectric focusing, preparative SDS/PAGE, and reversed phase HPLC. The Mr and pI values of these proteins were 14,000 and 9.10 for BP I, 27,500 and 8.48 for BP II, and 55,000 and 8.73 for BP III. These proteins differed significantly in their content of arginine, cysteine, proline, histidine, serine, and methionine. BP I appears to be the same protein as acylation-stimulating protein, but BP II and BP III appeared different from acylation-stimulating protein and other lipid carrier proteins. BP I, BP II, and BP III stimulated the incorporation of [14C]oleate into lipid esters in normal fibroblasts, an effect that was time and concentration dependent. In hyperapoB cells, BP II markedly increased (up to 9-fold) the incorporation of [14C]oleate into cholesteryl ester compared with that in normal cells; in addition, there was a 50% decrease in the stimulation of triglyceride acylation and cholesterol esterification with BP I. No difference between normal and hyperapoB cells was observed with BP III. In summary, the identification of another serum basic protein, BP II, led to the elucidation of another cellular defect in hyperapoB fibroblasts, enhanced cholesterol esterification, which may be related to the precocious atherosclerosis and abnormal lipoprotein metabolism seen in hyperapoB. PMID- 2247475 TI - Exon trapping: a genetic screen to identify candidate transcribed sequences in cloned mammalian genomic DNA. AB - Identification and recovery of transcribed sequences from cloned mammalian genomic DNA remains an important problem in isolating genes on the basis of their chromosomal location. We have developed a strategy that facilitates the recovery of exons from random pieces of cloned genomic DNA. The basis of this "exon trapping" strategy is that, during a retroviral life cycle, genomic sequences of nonviral origin are correctly spliced and may be recovered as a cDNA copy of the introduced segment. By using this genetic assay for cis-acting sequences required for RNA splicing, we have screened approximately 20 kilobase pairs of cloned genomic DNA and have recovered all four predicted exons. PMID- 2247474 TI - Sequence-specific interaction of Tat protein and Tat peptides with the transactivation-responsive sequence element of human immunodeficiency virus type 1 in vitro. AB - Bacterially expressed Tat protein of human immunodeficiency virus type 1 binds selectively to short RNA transcripts containing the viral transactivation responsive element (TAR). Sequences sufficient for Tat interaction map to the distal portion of the TAR stem-loop. We show that critical sequences for Tat binding are located in the single-stranded "bulge," but no requirement for specific "loop" sequences could be demonstrated. TAR RNA competed for complex formation, and TAR mutants exhibited up to 10-fold reduced affinity for Tat. Synthetic peptides containing the basic region of Tat bound selectively to TAR RNA and exhibited the same sequence requirements and similar relative affinities for mutant TAR RNA as the intact protein. These results suggest that Tat contains a small RNA-binding domain capable of recognizing TAR and implicate functional relevance for direct Tat-TAR interaction in transactivation. PMID- 2247477 TI - Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. AB - Diabetes and aging are commonly accompanied by arterio- and atherosclerosis. Infiltration of the arterial subendothelial intima by macrophages/monocytes is an important early event preceding the development of atheromatous lesions; these macrophages are known to produce mitogenic factors in early atherosclerotic lesions. It has been previously shown that, over time, vascular matrix accumulates proteins nonenzymatically modified by advanced glycosylation end products (AGEs). In view of the fact that macrophages/monocytes have AGE-specific receptors associated with the expression of several growth factors, we investigated the possibility that AGEs mediate initial monocyte-vessel wall interactions that occur before overt formation of vascular lesions. This study demonstrates that (i) in vitro- and in vivo-formed AGEs are chemotactic for human blood monocytes, (ii) sub-endothelial AGEs can selectively induce monocyte migration across an intact endothelial cell monolayer, and (iii) subsequent monocyte interaction with AGE-containing matrix results in the expression of platelet-derived growth factor. These results support the existing hypothesis that in vivo-forming glucose-derived protein adducts can act as signals for the normal turnover of senescent tissue protein by means of the AGE-specific receptor system. Time-dependent glucose-induced deposition of AGEs on matrix proteins may promote monocyte infiltration into the subendothelium. Subsequent AGE-triggered macrophage activation and consequent elaboration of proliferative factors may normally coordinate remodeling but may also lead to the diverse pathogenic changes typical of arterio- and atherosclerosis in diabetic or aging populations. PMID- 2247476 TI - Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast. AB - DNA sequencing was used to characterize 208 mutations induced in the SUP4-o tRNA gene of the yeast Saccharomyces cerevisiae by UVB (285-320 nm) radiation. The results were compared to those for an analysis of 211 SUP4-o mutations induced by 254-nm UVC light. In each case, greater than 90% of the mutations were single base-pair changes but G.C----A.T transitions predominated and accounted for more of the mutations induced by UVB than UVC. Double substitutions, single base-pair deletions, and more complex events were also recovered. However, UVB induced 3 fold more tandem substitutions than UVC and nontandem double events were detected only after irradiation with UVC. Virtually all induced substitutions occurred at sites where the pyrimidine of the base pair was part of a dipyrimidine sequence. Although the site specificities were consistent with roles for cyclobutane dimers and pyrimidine-pyrimidone(6-4) lesions in mutation induction, preliminary photoreactivation data implicated cyclobutane dimers as the major form of premutational DNA damage for both agents. Intriguingly, there was a preference for both UVB- and UVC-induced mutations to occur at sites where the dipyrimidine was on the transcribed strand. PMID- 2247478 TI - Aluminum access to the brain: a role for transferrin and its receptor. AB - The toxicity of aluminum in plant and animal cell biology is well established, although poorly understood. Several recent studies have identified aluminum as a potential, although highly controversial, contributory factor in the pathology of Alzheimer disease, amyotrophic lateral sclerosis, and dialysis dementia. For example, aluminum has been found in high concentrations in senile plaques and neurofibrillary tangles, which occur in the brains of subjects with Alzheimer disease. However, a mechanism for the entry of aluminum (Al3+) into the cells of the central nervous system (CNS) has yet to be found. Here we describe a possible route of entry for aluminum into the cells of the CNS via the same high-affinity receptor-ligand system that has been postulated for iron (Fe3+) delivery to neurons and glial cells. These results suggest that aluminum is able to gain access to the central nervous system under normal physiological conditions. Furthermore, these data suggest that the interaction between transferrin and its receptor may function as a general metal ion regulatory system in the CNS, extending beyond its postulated role in iron regulation. PMID- 2247479 TI - Xenopus Y-box transcription factors: molecular cloning, functional analysis and developmental regulation. AB - We describe the cloning and characterization of two cDNAs from Xenopus laevis that encode sequence-specific DNA binding proteins called FRG Y1 and FRG Y2 (frog Y-box proteins 1 and 2). During oogenesis and embryogenesis, the genes encoding these proteins are differentially expressed. FRG Y1 mRNA is present in oocytes, embryos, and all adult tissues examined, whereas FRG Y2 mRNA is found only in testis and immature oocytes. The FRG Y1 and FRG Y2 proteins are shown to stimulate transcription from a promoter containing a Y box (CTGATTGGCCAA). This promoter element is found in both mammalian major histocompatibility complex class II and Xenopus germ-cell-specific genes. FRG Y1, FRG Y2, and a human Y-box binding protein are homologous and represent a distinct family of sequence specific DNA binding proteins. We identify protamine-like regions that are present within this family of transcription factors, suggesting that they use unusual means of binding to DNA. PMID- 2247480 TI - Overexpression of normal and mutated forms of HRAS induces orthotopic bladder invasion in a human transitional cell carcinoma. AB - Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that accurately reflects their clinical malignant status in the original host. Thus, such a system allows a unique opportunity to analyze the genetic events involved in the conversion of low-grade bladder cancer, the vast majority of which are curable, to the high-grade life-threatening form of the disease. Since 5-10% of transitional cell carcinomas (TCCs) have been shown to contain a mutated HRAS gene, and protein expression levels of all forms of HRAS have been correlated with TCC progression, we chose to study the contribution of the HRAS oncogene in bladder tumor progression. We evaluated the effects of transfection of normal or mutated HRAS genes into a human TCC, called RT-4, that behaves as a superficial noninvasive papillary tumor after transurethral orthotopic inoculation into athymic nude mice. We found that overexpression of either transfected normal or mutated HRAS genes converted RT-4 cells to express an invasive phenotype remarkably similar in nature to the clinical behavior of high-grade bladder carcinomas. These results suggest a role for overexpressed normal or mutated RAS genes in human bladder carcinoma progression, and highlight the importance of using orthotopic inoculation systems for evaluation of the contribution of oncogenes to malignant tumor progression. PMID- 2247483 TI - Questions related to the effects of therapy on biology and kinetics of the surviving tumor. PMID- 2247481 TI - Evidence for the maintenance of hematopoiesis in a large animal by the sequential activation of stem-cell clones. AB - To test if hematopoiesis can be maintained by the sequential activation of stem cell clones, we performed autologous marrow transplantations with limited numbers of cells in cats heterozygous for the X chromosome-linked enzyme glucose-6 phosphate dehydrogenase (G6PD) and observed the G6PD phenotypes of erythroid and granulocyte/macrophage progenitors over time. The animals were the female offspring of Geoffroy male and domestic female cats. In repeated studies of marrow from control animals (n = 5) or experimental animals prior to transplantation (n = 3), the percent of progenitors with domestic-type G6PD did not vary. After transplantation, the peripheral blood counts, marrow morphologies, frequencies of progenitors, and progenitor cell cycle kinetics returned to normal. However, abrupt and significant fluctuations were seen in the G6PD type of progenitors from each cat during the 1-1.5 years of observation. These data cannot be explained if there were either a large or constant population of active stem cells and thus imply, in a large-animal system, that hematopoiesis was maintained through clonal succession. A stochastic model was developed to estimate the numbers of active clones and their mean lifetimes. PMID- 2247482 TI - Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys. AB - Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes. PMID- 2247485 TI - Surgery, kinetics and biological considerations in planning adjuvant therapy protocols. PMID- 2247484 TI - Biology of residual breast cancer after therapy: a kinetic interpretation. PMID- 2247486 TI - Growth control of normal and malignant breast epithelium. PMID- 2247487 TI - Studies of EGF-mediated growth control and signal transduction using the MDA-MB 468 human breast cancer cell line. PMID- 2247488 TI - Effects of the initial chemotherapy on subsequent therapy. PMID- 2247489 TI - Growth control in leukemia. AB - Quantitative assays for individual hematopoietic progenitors have provided a powerful approach to the assessment of changes in the absolute and relative numbers of primitive cells in the affected tissues of individuals with CML. These techniques have also been usefully coupled to other ways of assessing these cells to confirm their malignant nature by cytogenetic analysis and to establish and characterize abnormalities in the regulation of their numbers and turnover. A culture system that allows primitive normal and leukemic hematopoiesis to be maintained for many weeks has been developed. This system has been found to reproduce the cardinal features of primitive hematopoietic cell regulation in vivo and its use has allowed important progress to be made in characterizing the molecular basis of stromal cell regulation of primitive hematopoietic cells. Nevertheless, a large gap still remains between our knowledge of the genes that are altered in CML (or other malignancies) and the biological changes underlying the deregulation of growth that is characteristic of malignancy in general. Further exploitation of in vitro systems that allow this deregulation to be analyzed and manipulated appears to offer promise towards bridging this gap in the future. PMID- 2247490 TI - The biology of cancer metastasis. AB - The formation of a metastasis entails a complex sequence of events with the end result dependent on the interaction of malignant cells with host factors. Intrinsic properties of the metastatic tumor cells, including production of proteolytic enzymes, cell surface properties, adhesiveness, and the ability to grow in a distant organ environment, act in concert to influence the tumor cells' interactions with host cells in forming metastases. Life-threatening metastases are formed only by those tumor cells that have survived all steps in a process that has been shown in many experimental studies to be a highly selective event. The results of studies on the distribution of radiolabelled mouse melanoma cells injected into syngeneic mice support the concept that the fate of tumor cells released into the bloodstream is determined by sequential and selective events, and introduces a third regulatory factor. Cells endowed with metastatic properties, isolated by cloning a heterogeneous tumor or selected from a metastasis, have a higher probability of forming metastases than cells not so endowed, yet this probability is not 100%. Metastasis should thus be considered as a selective, sequential and stochastic process. Interruption of the process at any stage will prevent the formation of metastatic disease. Hence, a better understanding of the metastatic process will provide the basis for rational approaches for the prevention or destruction of this most fatal aspect of cancer. PMID- 2247491 TI - Macrophages, metastasis and immunity. PMID- 2247492 TI - Development of myelorestorative and immunotherapeutic properties of cytokines. PMID- 2247493 TI - Cellular maturation and oncogene expression during drug-induced differentiation in vitro: a brief review. PMID- 2247494 TI - Proliferative and vascular responses to cytoreduction in solid tumor models. PMID- 2247495 TI - Mammary gland as a model for studies of gene expression in normal and malignant cells. PMID- 2247496 TI - Leaky tumor vessels: consequences for tumor stroma generation and for solid tumor therapy. AB - Our results may be summarized as follows: 1) The tumor microvasculature is hyperpermeable to macromolecular tracers, as compared with the vessels supplying many normal tissues. 2) In the case of the several solid transplantable animal tumors studied, leaky vessels are well-differentiated venules and small veins, lined by a continuous endothelium with mostly closed interendothelial junctions. Leaky vessels are concentrated at the tumor-host interface and in bands of stroma interspersed between tumor nodules; in contrast, tumor-penetrating vessels exhibit little or no leakage of macromolecules. 3) The mechanisms of vascular leakage have yet to be established but apparently cannot be attributed to vessel immaturity, structural defects, interendothelial cell gaps, vessel injury or development of a specialized (e.g., fenestrated or sinusoidal) endothelium. 4) Macromolecules that extravasate from leaky vessels also accumulate in tumors at higher concentrations than in the blood or control tissues. Increased tracer accumulation in tumors is attributable to increased tracer influx and possibly also to reduced tracer clearance (perhaps resulting from the absence or obstruction of lymphatics). However, the high molecular weight FITC-D tracers that extravasate into solid tumors remain largely confined to tumor stroma, do not extend far from the vessels from which they leaked, and make little contact with malignant cells. 5) In contrast, smaller tracers (e.g., 3 kD FITC-D) extravasate from tumor-penetrating vessels, from the capillaries of normal tissues, as well as from hyperpermeable vessels, and, unlike larger FITC-D, diffuse readily throughout solid tumors. PMID- 2247497 TI - Embryonic mechanisms for abrogating the malignancy of cancer cells. PMID- 2247498 TI - The chemoprevention of human cancer: an overview. PMID- 2247499 TI - Retinoids and breast cancer. PMID- 2247500 TI - Comments on future developments of cancer therapy taking into consideration tumor biology and kinetics. Part I. PMID- 2247501 TI - Regulation of growth in normal and neoplastic cell populations by a tissue sizer mechanism: therapeutic implications. PMID- 2247502 TI - Tumor differences, drug differences, treatment design differences, and effects on therapeutic outcome (degree and duration of therapeutic response). PMID- 2247503 TI - Genetic and kinetic factors in the drug resistance of micrometastatic disease. AB - Of all of the potential scenarios described above the last is perhaps the most pessimistic or at least the one which will require the greatest advances in understanding and modulating tumor cell behaviour. If this type of phenomenon is indeed the basis of treatment failure in stage II breast cancer then it will be difficult to demonstrate this directly by any of the techniques currently available. If consistent application of the strategies dictated by other treatment failure scenarios fail to yield progressively improving results then one might have to infer this more pessimistic situation indirectly. This carries with it the implication that ultimate and truly satisfactory control of micro metastatic breast cancer will have to await further fundamental discoveries involving the growth parameters and properties of tumor cells during the time when they exist as small isolated colonies. PMID- 2247504 TI - Physical mapping of the long arm of chromosome 21. PMID- 2247505 TI - The ETS family of genes: structural analysis, gene products, and involvement in neoplasia and other pathologies. PMID- 2247506 TI - Detailed genetic linkage map of human chromosome 21: patterns of recombination according to age and sex. AB - A detailed genetic linkage map of human chromosome 21 will allow the rapid regional assignment of future genes and DNA markers to this autosome. It will also facilitate the precise mapping of the genes responsible for the DS phenotype and the defect causing FAD. This map can also be used to implicate genes involved with specific features of the DS phenotype by permitting the delineation of finite regions of chromosome 21 which are duplicated in patients with partial trisomy 21, and who manifest select symptoms of the DS phenotype. In the case of FAD, most pedigrees are not ideally structured for genetic linkage analysis since affected individuals die relatively soon (6-8 years) after the onset of symptoms. By first establishing the genetic relationships of DNA markers in the vicinity of the FAD defect, multipoint analyses of these markers can then be performed in FAD families. Multipoint analysis carries a greater probability of identifying markers flanking the FAD locus thereby providing landmarks for cloning attempts aimed at isolating and characterizing the FAD gene defect. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males, and significantly higher recombination in females in the pericentromeric region between D21S1/S11 and D21S13/S16. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have identified a statistically significant downward trend in in the frequency of crossovers in the most telomeric portion chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the sub centromeric region of the chromosome where recombination in females is overall higher than in males. Future confirmation of these results in combination with investigations aimed at deciphering the role played by recombination in promoting normal segregation during meiosis should help to elucidate the potential relevance of these findings to the etiological basis of nondisjunction. PMID- 2247507 TI - Genes on chromosome 21 and cancer. PMID- 2247508 TI - Molecular analysis of cystathionine beta-synthase--a gene on chromosome 21. PMID- 2247509 TI - Translocations and rearrangements involving chromosome 21. PMID- 2247510 TI - Alpha and beta satellite sequences on chromosome 21: the possible role of centromere and chromosome structure in nondisjunction. PMID- 2247511 TI - Isolation and characterization of DNA probes for human chromosome 21. AB - A coordinated effort to map and sequence the human genome has recently become a national priority. Chromosome 21, the smallest human chromosome accounting for less than 2% of the human genome, is an attractive model system for developing and evaluating genome mapping technology. Several strategies are currently being explored including the development of chromosome 21 libraries from somatic cell hybrids as reported here, the cloning of chromosome 21 in yeast artificial chromosomes (McCormick et al., 1989b), and the construction of chromosome 21 libraries using chromosome flow-sorting techniques (Fuscoe et al., 1989). This report describes the approaches used to identify DNA probes that are useful for mapping chromosome 21. Probes were successfully isolated from both phage and cosmid libraries made from two somatic cell hybrids that contain human chromosome 21 as the only human chromosome. The 15 cosmid clones from the WA17 library, reduced to cloned DNA sequences of an average size of 3 kb, total 525 kb of DNA which is approximately 1% of chromosome 21. From these clones, a set of polymorphic DNA markers that span the length of the long arm of chromosome 21 has been generated. All of the probes thus far analyzed from the WA17 libraries have been mapped to chromosome 21 both by physical and genetic mapping methods. It is therefore likely that the WA17 hybrid cell line contains human chromosome 21 as the only human component, in agreement with cytogenetic observation. The 153E7b cosmid libraries will provide an alternative source of cloned chromosome 21 DNA. Library screening techniques can be employed to obtain cloned DNA sequences from the same genetic loci of the two different chromosome 21s. Comparative analysis will allow direct estimation of DNA sequence variation for different regions of chromosome 21. Mapped DNA probes make possible the molecular analysis of chromosome 21 at a level of resolution not achievable by classical cytogenetic techniques (Graw et al., 1988; Van Keuren et al., 1989). Methods based on using region-specific chromosome 21 DNA probes and fluorescence in situ hybridization show promise for the rapid diagnosis of trisomy 21 (Lichter et al., 1988). The continued development of chromosome 21 DNA probes and advances in the technology of molecular cytogenetics will facilitate the study of the genetic organization of chromosome 21 and its role in the pathogenesis of Down syndrome. PMID- 2247512 TI - Microdissection and microcloning of human chromosome 21. AB - Detailed physical mapping of specific genomic regions require many DNA probes isolated from the region of interest. A more direct approach is to physically dissect the region and to clone the dissected DNA sequences in small volume using a microcloning procedure. Metaphase chromosome preparations can be used for microdissection. The dissected chromosome fragments containing picograms of DNA are treated with proteinase K/SDS and EcoR1, and ligated to phage vector arms. All these microcloning steps are performed under the microscope in nanoliter volumes. After ligation, the extract is in vitro packaged and plated on selective bacterial host. The recombinant microclones are isolated and characterized for use as probes for physical mapping and molecular studies of the dissected region. These microtechniques have been developed and applied to human chromosome 21. This approach appears to be particularly useful in saturation cloning and mapping of refined chromosomal regions to facilitate search for disease genes mapped to a particular region. PMID- 2247513 TI - Brain death--still a controversy. PMID- 2247514 TI - Human responses to epidemics and illness. PMID- 2247515 TI - The incredible lightness: antidote for the heaviness of illness. PMID- 2247516 TI - Surgeons and their communities: a message about giving. PMID- 2247517 TI - Clinical investigation: clear problems, cloudy solutions. PMID- 2247518 TI - A visit to Maimonides' grave. PMID- 2247519 TI - No second act. PMID- 2247520 TI - The Court and Webster: ethics, politics, and abortion--a panel discussion. PMID- 2247522 TI - Clinical investigation and investigators revisited. PMID- 2247521 TI - Between the lines. PMID- 2247523 TI - Past and present. Always the sweatshop? PMID- 2247524 TI - Halsted's Carolina connection: the story of Caroline Hampton. PMID- 2247525 TI - [Effect of pulsating electromagnetic field therapy on cell volume and phagocytosis activity in multiple sclerosis and migraine]. AB - PEMF treatment was studied in 10 patients with multiple sclerosis and 10 patients with migraine. In both patients' groups a single treatment induced a significant rise of yeast particle uptake by blood granulocytes. The percentage of phagocytizing cells was increased in migraine patients only. In both patients' groups 20 PEMF treatments caused a reduction of particle uptake, whereas the percentage of phagocytizing cells remained unchanged. In migraine patients the opsonic capacity of serum and the mean cell volume of erythrocytes, lymphocytes and granulocytes were initially reduced, but increased during the course of 20 PEMF treatments. The biphasic changes of cell volume and phagocytic activity are interpreted as a result of counter-regulation of the organism in response to the primary PEMF effect. PMID- 2247526 TI - [Factors affecting the disease course in multiple sclerosis]. AB - This study investigate the significance of various data of patient's and family's history according to the disease activity of MS. 350 patients with definitive MS were divided into two groups according to a different clinical course. There was no difference in the frequency of the registered factors between these two groups. Our conclusion is, that the evaluated factors don't have prognostic significance in the course of MS. The results support the model of a phase characteristic course of MS which has been suggested by Fog and Linnemann. PMID- 2247527 TI - [Cerebrospinal fluid cytologic diagnosis--possibilities and limits]. AB - Findings of functionally active and proliferating cells in CSF, such as granulocytes, macrophages, lymphoid cells and blastoma cells are of diagnostic importance in pathological reactions of meninges. Such findings have a special significance in different phases in the course of meningoencephalitis, subarachnoid haemorrhage and infiltrations of neoplasms with subependymal localization which can not be obtained even by modern methods in neuroradiology. A correct diagnostic assessment is only given by knowledge and in consideration of all clinical and laboratory findings. The diagnostic value is limited in cases of deeply intracerebral localized diseases, of chronic recurrent processes, of cases with previous lesions or of concommitant symptoms because the results are atypical. PMID- 2247528 TI - [Results of a study of glucocorticoid receptors in lymphocytes of patients with endogenous depression]. AB - Increased plasma cortisol levels are found not only in patients with Cushing disease but also in patients suffering from endogenous depression. Because patients with endogenous depression fail to show any clinical signs of Cushing disease, it is supposed that the cells of these patients are relatively resistant to increased glucocorticoid levels. To test this hypothesis 20 patients with endogenous depression and 20 healthy controls were examined for plasma cortisol level and modulation of mitogen induced lymphocyte transformation by glucocorticoids. Results point to a relative resistance of patient's T-lymphocyte transformation to the inhibitory effect of glucocorticoids when compared with controls. PMID- 2247529 TI - [Results of combined treatment of malignant brain tumors with various cytostatic protocols]. AB - Nowadays best results in the treatment of malignant brain tumors can be obtained with an interdisciplinary combined treatment (operation, radiation, antineoplastic chemotherapy). We treated 83 patients with gliomas after operation with a combined radiation/chemotherapy. Chemotherapy was performed by two different schemas (Israel n = 49, COMP n = 34). Both groups had the same structure concerning the 10 most important prognostic factors. The median survival time was found to be 26.1 months in the Israel-group and 22.8 months respectively in the COMP-group. The number of the long-time survivors is increasing in the COMP-group. PMID- 2247530 TI - [Psychosocial management of glioma patients treated with combined therapy]. AB - Based on an empirical study it is pointed out that psychosocial care of patients with glioma differs in some points from that of other cancer patients. The first essential difference is that the emotional involvement of the care staff is not as intensive as those of other cancer patients. Other differences concern some illness- and therapy related effects such as family problems or monotony problems resulting from the longterm therapy. These specific problems are described in detail. PMID- 2247531 TI - [Hypothetical aspects of the preventive effectiveness of controlled reflex and stimulation therapy (exemplified by acupuncture and PuTENS) in migraine]. AB - On the basis of lang term therapeutical and experimental experience with acupuncture and punctual transcutaneous electrical nervestimulation (PuTENS) and in connection with the present neurophysiologically knowledge the results of reflextherapy and stimulatory-therapy in migrain are discussed. The established analgetic, vascular, musclerelaxing and reflectory effects of acupuncture may in part explain a causative influence on migraine. Trigger mechanisms siderably reduced and the vegetative state are favourable influenced. PMID- 2247532 TI - [Pain and pain perception]. AB - Pain is both sensual perception and sense of touch, and it leads to emotional change of health, which has an effect back to a pain perception. Experience of pain is modified by intern and extern influences, and it can appear very multiformly in the chronicity. A part of these factors are described. PMID- 2247533 TI - Pseudo-random mating systems for 3-allele loci. AB - A random mating population attains equilibrium by the Hardy-Weinberg law. By demonstrating some simple examples for 2-allele loci, Li (1988) showed that a nonrandom mating population of certain mating patterns may also attain equilibrium. He called such a type of population a pseudo-random mating population. Tai (1990), then, gave a generalized representation of these pseudo random mating systems. In this paper the clear patterns of pseudo-random mating behavior for a 3-allele locus are derived. Both autosomal and sex-linked systems are discussed. The study of these mating patterns provides a way to understand the complicated mating system of a population, which usually is only with difficulty realized through sampled individuals from that population. PMID- 2247534 TI - Effect of ethanol intake on rat liver mitochondrial respiration and oxidative phosphorylation. AB - The effect of ethanol intake on liver mitochondrial functions was investigated by feeding rats with a liquid isocaloric diet containing various concentrations of ethanol. We found that after feeding the liquid diet for 2 to 3 months, the body weight of rats did not show a significant difference between treated and control groups. However, the mitochondrial respiration rate decreased significantly with the increase of ethanol concentration in the diet. We found that when the rats were fed on 10.8% ethanol, the average succinate-supported State 3 respiration rate decreased from 54.5 to 44.8 nmol O2/min/mg and the glutamate-malate supported State 3 respiration rate decreased from 38.8 to 23.6 nmol O2/min/mg as compared with the control. Interestingly, we noted that ethanol intake caused a more drastic effect on State 3 respiration than on State 4 respiration, irrespective of the substrate utilized by the mitochondria. In addition, the respiratory control and ADP/O ratios were found to decrease concomitantly with the increase of ethanol level in the diet. Moreover, we found that the effect of ethanol on both respiratory control and ADP/O ratios of liver mitochondria was more pronounced in glutamate-malate-supported respiration than succinate supported respiration. These results clearly demonstrate that ethanol intake by the rat can cause impairment of liver mitochondrial respiration and oxidative phosphorylation, and that these effects are exerted through damage to mitochondrial membranes. PMID- 2247535 TI - Isolation and partial characterization of Bermuda grass-pollen allergen: BG-60b. AB - Our earlier studies have shown that the pollen of Bermuda grass (Cynodon dactylon)-pollen contain at least 12 IgE-binding proteins which can be analyzed by the immunoblot technique. One of the highly active components was found to be a basic protein with a molecular weight of 60,000 daltons, designated as BG-60. This component was showed to consist of a group of proteins. One of them, BG-60a (pI 9.7), has been isolated and characterized. In this study, we have further isolated and characterized the second component of the antigen, designated as BG 60b. Its purity was demonstrated by gel electrophoresis experiment and antigen antibody precipitation studies. The antigen is of glycoprotein nature with a pI of 10.0. It exhibits IgE-binding activity and shows cross-reactivity to antigen BG-60a in double diffusion. Its chemical and physical properties are similar to antigen BG-60a. PMID- 2247536 TI - Ontogeny of the FMRFamide-immunoreactivity in the rat forebrain and diencephalon. AB - Ontogeny of the FMRFamide (molluscan cardioexcitatory neuropeptide)-containing structures in the forebrain and diencephalon of the rat was investigated by employing immunohistochemical methods. FMRFamide-like immunoreacted (FMRF-IR) fibers first appeared in the borders of the periventricular zone and the preoptic area at embryonic day 18 (E18). Toward birth, the FMRF-IR fibers gradually increased both in immunoreactivity and in number in these areas. A pronounced increase in FMRF-IR was also found in the septum, the arcuate nucleus, the median eminence, the paraventricular nucleus and the amygdaloid complex. A few FMRF-IR fibers appeared at the prenatal stage in the caudate nucleus, the bed nucleus of the stria terminalis, the dorsomedial nucleus and the cortex. The first FMRFamide immunoreactive neurons were seen in the caudate-putamen and the amygdaloid complex at E21. These FMRF-IR cells increased in immunoreactivity and a significant number of cells was noted in these nuclei in the adult rat. The highest density of FMRF-IR neurons, especially in the amygdala and tuberal hypothalamic area, was detected at postnatal two weeks (P15). FMRFamide-like immunoreactivity in the forebrain and diencephalon appeared in the cell fibers prior to that observed in the cell bodies. This may suggest that some of the immunoreacted fibers may have originated from the lower areas of the rat brain. High densities of FMRF-IR cells present in the embryonic and early postnatal stages may indicate that FMRFamide is an important factor involved in developmental organization of the central nervous system. These results also indicate a differential genesis of FMRF-IR neuronal groups in different regions. PMID- 2247537 TI - Circadian rhythms of feeding and drinking behavior of rats aged from 3 to 21 months. AB - Circadian rhythms and patterns of feeding and drinking behavior of 8 male and 8 female Long-Evans rats were followed from 3 months of age (mo) to 21 mo at 3 month intervals. Meal number, draft number and feeding events/min/meal of female rats were greater than those of male rats of the same age, while intermeal intervals, interdraft intervals and licking events/min/draft of male rats were greater than those of female rats. Sex differences of meal number, intermeal intervals and feeding events/min/meal as a group disappeared by 21 mo. Light/dark differences of meal number of both sexes, intermeal intervals of females and licking events/min/draft of males as a group also disappeared by 21 mo and difference of feeding events/min/meal disappeared by 15 and 18 mo in males and females, respectively. Occurrence of age-related change varied from 6 to 21 mo depending upon the parameter of the behavior and period (light or dark). Meal number and feeding events/min/meal showed the most clear-cut age-related changes and the decline occurred earlier and was more remarkable in males than in females. The age-related decline of patterns and the power spectrum of drinking behavior was less prominent than that of feeding behavior. These results indicate that feeding behavior is more affected by the aging process than is the drinking behavior of rats, and that male rats show more prominent aging changes than females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247538 TI - The information-loss model: a mathematical theory of age-related cognitive slowing. AB - A model of cognitive slowing is proposed with the following assumption: Information is lost during processing, processing occurs in discrete steps with step duration inversely related to the amount of information currently available, and the effect of aging is to increase the proportion of information lost per step. This model correctly predicts a positively accelerated relation between latencies of older and younger adults and provides a unified account of the effects of task complexity, practice, speed-accuracy tradeoffs, and fluctuations in individual performance. Strong support for the thesis that cognitive slowing is global, and not localized in specific age-sensitive components, is provided by the fact that the model accurately predicts the latencies of older adults on the basis of those of younger adults, without regard to the nature of the task, across a latency range of nearly 2 orders of magnitude. PMID- 2247539 TI - Word identification in reading and the promise of subsymbolic psycholinguistics. AB - The vast literature concerning printed word identification either contradicts or provides ambiguous support for each of the central hypotheses of dual-process theory, the most widely accepted theory of printed word identification. In contrast, clear, positive support exists for an alternative subsymbolic approach that includes a central role for the process of phonologic coding. This subsymbolic account is developed around a covariant learning hypothesis, derived from a design principle common to current learning algorithms within the subsymbolic paradigm. Where this hypothesis applies, and it may apply broadly, it predicts a common empirical profile of development. PMID- 2247540 TI - A theory of visual attention. AB - A unified theory of visual recognition and attentional selection is developed by integrating the biased-choice model for single-stimulus recognition (Luce, 1963; Shepard, 1957) with a choice model for selection from multielement displays (Bundesen, Pedersen, & Larsen, 1984) in a race model framework. Mathematically, the theory is tractable, and it specifies the computations necessary for selection. The theory is applied to extant findings from a broad range of experimental paradigms. The findings include effects of object integrality in selective report, number and spatial position of targets in divided-attention paradigms, selection criterion and number of distracters in focused-attention paradigms, delay of selection cue in partial report, and consistent practice in search. On the whole, the quantitative fits are encouraging. PMID- 2247541 TI - Parts of activities: reply to Fellbaum and Miller (1990). AB - If people believe that one activity is a kind of another, they also tend to believe that the second activity is a part of the first. For example, they assert that deciding is a kind of thinking and that thinking is a part of deciding. Fellbaum and Miller's (1990) explanation for this phenomenon is based on the idea that people interpret part of in the domain of verbs as a type of logical entailment. Their explanation, however, suffers from at least 2 deficiencies. First, it fails to account for parallel effects with nouns (e.g., a contest is a kind of an activity, and an activity is a part of a contest). Second, it contains a flaw that incorrectly predicts many activities to be parts of each other (e.g., coming is part of going and going part of coming). However, a hypothesis Rips and Conrad (1989) originally proposed for the kind-part reciprocal effect avoids both of these difficulties. PMID- 2247542 TI - On the dynamics of generalization. PMID- 2247543 TI - Neural nets for generalization and classification: comment on Staddon and Reid (1990) AB - The neural net model of Staddon and Reid (1990) explains exponential and Gaussian generalization gradients in the same way as the diffusion model of Shepard (1958). The "cognitive" generalization theory of Shepard (1987), which also has been implemented as a connectionist network, goes beyond both of these models in accounting for classification learning. PMID- 2247545 TI - Cognitive event-related potential components during continuous recognition memory for pictures. AB - Event-related brain potentials (ERPs) were recorded from 28 young adult subjects during a continuous recognition memory paradigm, with pictures as stimuli. Subjects were required to determine on each trial if the picture was "new" (never before presented) or "old" (seen previously). To assess differences between primary and secondary memory, old items were presented after lags of 2, 8, and 32 intervening pictures (equiprobable) following their first presentation. The results suggested that a negativity (Cz maximum) at 300 ms was the most likely candidate for the brain event reflecting the retrieval of the item from memory. Old/new effects were modulated by two types of activity, both of which were larger in the ERPs elicited by new items. The earlier of these, possibly similar to the N400, had a duration from about 250-600 ms, began with the N300 deflection, and lasted until "P300" began to decrement. The other was positive, resembled "positive slow wave," onset as P300 began to decrement, and lasted until the end of the recording epoch. There were no consistent effects of item lag on the behavioral data or on any of the ERP components, suggesting that for pictorial stimuli, the distinction between the two types of memory store, primary (i.e., immediate memory) and secondary (newly learned information), may not be relevant. In consonance with the lack of lag effects, it was suggested that the lack of a robust subsequent memory effect on the ERP waveform could have been due to the use of pictures, which may have required less elaborative processing in order to be encoded at input. PMID- 2247544 TI - Influences of the normal menstrual cycle on physiologic functioning during behavioral stress. AB - The purpose of this study was to evaluate the influence of the normal menstrual cycle on lipoprotein, cardiovascular, and neuroendocrine stress responses. Fifteen normally-cycling, healthy women participated in a series of behavioral tasks during the menstrual, follicular, and luteal phases of their menstrual cycle. These women had established menstrual cycle regularity for the three months prior to enrollment in this study, were free from menstrual cycle disturbances, biochemically confirmed that they ovulated, and displayed appropriate patterns of reproductive hormone fluctuations during the study period. Heart rate, blood pressure, low density lipoprotein-cholesterol, and total cholesterol all demonstrated significant elevations from baseline levels during tasks. No differences in the magnitude of stress responses during the three menstrual cycle phases were noted for any physiological variable. We conclude that the hormonal fluctuations that occur in healthy, normally-cycling women during the menstrual cycle do not influence the stress responses that were investigated here. Significant influences of menstrual cycle phase previously reported in the literature, albeit not in a consistent direction, may have been due to the recruitment of women with menstrual cycle irregularities, and to the failure to adequately verify menstrual cycle phase. PMID- 2247546 TI - Cardiovascular and metabolic activity at rest and during psychological and physical challenge in normotensives and subjects with mildly elevated blood pressure. AB - Heart rate, systolic and diastolic blood pressure, and respiratory and metabolic activity were recorded prior to and during mental arithmetic and a video game task in 20 young men with mildly elevated casual systolic blood pressures. Twenty five unambiguously normotensive young men were tested under the same protocol. For pretask baseline physiological activity, group differences emerged for all cardiovascular and metabolic variables; thus the elevated blood pressure group displayed not only higher resting cardiovascular levels than normotensive subjects, but higher levels of metabolic activity too. With regard to change in physiological activity from rest to task, the group with mildly elevated blood pressure showed reliably larger increases in heart rate to the mental arithmetic task than the normotensive subjects. These effects, however, were not paralleled by group differences in metabolic activity increase. Physiological measures were also taken prior to and during graded dynamic exercise. The subsequent calculation of individual heart rate-oxygen consumption exercise regression lines allowed the comparison of actual and predicted heart rates during psychological challenge. The subjects with mildly elevated blood pressure displayed significantly greater discrepancies between actual and predicted heart rate values than normotensives during the psychological tasks in general and mental arithmetic in particular. Group differences in physiological activity during exercise largely reflected the pattern seen at rest. A possible exception here was systolic blood pressure. Not only were systolic blood pressure levels higher throughout the exercise phase for mildly elevated blood pressure subjects, but this group evidenced more of an increase from rest to exercise than the normotensives. PMID- 2247547 TI - Multiple sources of P3b associated with different types of information. AB - This experiment investigated how the P3a, P3b, and Slow Wave components of the event-related brain potential (ERP) respond to manipulations of the nature, timing, and extent of information delivery. There were two experiments in which the total amount of task information was distributed between pairs of successive stimuli (S1 and S2) within each trail. The task was to predict the relation between S1 and S2. In Experiment 1, the S1 could resolve no, partial, or all uncertainty with respect to the prediction outcome (correct or incorrect). Each S1 delivered three types of information: 1) outcome information--which resolved the subjects' uncertainty about the correctness of their prediction; 2) procedural information--which resolved uncertainty about how much outcome information would be delivered by S1; and 3) memory information--the identity of S1, which had to be stored for subsequent comparison with S2. In Experiment 2, the activity of these components was contrasted in two conditions in which the S1 delivered either memory information alone or both memory and procedural information. P3a and Slow Wave were sensitive only to outcome information. P3b was sensitive to all three types of information, and its scalp topography varied as a function of the type of information. The topographic variations indicate that P3b is not a unitary phenomenon but rather is a composite of activity arising from multiple intracranial sources of bioelectric activity. PMID- 2247548 TI - Rudimentary physiological effects of mere observation. AB - Complex social factors can influence physiological activity, behavior, and health, but little is known about how essential components of these factors (e.g., human association, observation) affect human physiology. To begin to address this issue, an experiment was conducted to contrast predictions from social facilitation, distraction/conflict, and physiological reactivity formulations regarding the physiological effects of mere observation. Skin conductance and heart rate were measured surreptitiously from 27 women during a period in which they believe that the experimenter was simply calibrating auditory and physiological recording equipment. Approximately half of the subjects were led to believe that they could be observed by the experimenter during this period, and the remainder were led to believe that they could not be observed. Following baseline recordings, a series of 10 orienting tones were presented. Predictions from the physiological reactivity formulation were supported: (a) no differences in basal levels of somatovisceral activity were found as a function of mere observation; (b) mere observation enhanced the skin conductance response to the initial orienting tone; and (c) these physiological differences were punctate, quickly dissipating and quickly habituating. Hence, mere observation has subtler physiological effects than thought previously. Implications are discussed regarding the possible mechanism underlying the stress enhancing and stress-buffering effects of human association, and regarding the effects social and contextual factors may have in psychophysiological research. Results from an international survey, based on the responses of 57 authors of articles that have appeared in Psychophysiology since 1983, are reported to inform the latter discussion. Results suggest that, even when social factors in psychophysiological research are minimized or held constant within studies, subtle differences in the social context across studies within and across laboratories may contribute to the appearance that psychophysiological relationships are unreliable. PMID- 2247549 TI - Psychophysiological reactivity in cardiac transplant recipients. AB - To assess the contribution of the heart's autonomic innervation to reactivity to psychological stressors, hemodynamic responsiveness of the denervated human heart was examined in two studies. In Study I, cardiac output measured by thermodilution, heart rate, and systolic and diastolic blood pressure responses to a 4-min mental arithmetic task were studied in 7 cardiac transplant patients during routine post-transplant cardiac catheterization. In Study II, 6 cardiac transplant patients, 5 normal controls, and 5 renal transplant patients participated in a 78-min psychophysiological stress protocol during which heart rate, systolic and diastolic pressure, and cardiac output (measured noninvasively by impedance cardiography) as well as serum epinephrine and norepinephrine were measured at baseline and while subjects performed mental arithmetic and reaction time tasks. In Study I, transplant patients showed significant increases, relative to baseline, in heart rate, systolic blood pressure, and cardiac output in response to mental arithmetic. The diastolic blood pressure response was marginally significant. In Study II, mental arithmetic produced significant reactivity in systolic blood pressure and marginally significant increases in heart rate and diastolic blood pressure in cardiac transplant patients. Reaction time produced only marginally significant diastolic blood pressure reactivity. Hemodynamic reactivity of the cardiac transplant group generally was lower than that of the two innervated groups, which generally were similar to each other. Although the small number of subjects makes conclusions tentative, these data suggest that: 1) Cardiac transplant patients are capable of significant reactivity to psychological stressors despite the absence of innervation of the heart, and 2) reactivity to these stressors is diminished relative to innervated control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247550 TI - Cross-modal selective attention effects on retinal, myogenic, brainstem, and cerebral evoked potentials. AB - Short latency evoked potentials were recorded during a cross-modal selective attention task to evaluate recent proposals that sensory transmission in the peripheral auditory and visual pathways can be modified selectively by centrifugal mechanisms in humans. Twenty young adult subjects attended in turn to either left-ear tones or right-field flashes presented in a randomized sequence, in order to detect infrequent, lower-intensity targets. Attention-related enhancement of longer-latency components, including the visual P105 and the auditory N1/Nd waves and T-complex, showed that subjects were able to adopt a selective sensory set toward either modality. Neither the auditory evoked brainstem potentials nor the early visual components (electroretinogram, occipito temporal N40, P50, N70 waves) were significantly affected by attention. Measures of retinal B-waves were significantly reduced in amplitude when attention was directed to the flashes, but concurrent recordings of eyelid electromyographic activity and the electro-oculogram indicated that this effect may have resulted from contamination of the retinal recordings by blink microreflex activity. A trend toward greater positivity in the 15-50 ms latency range for auditory evoked potentials to attended tones was observed. These results provide further evidence that the earliest levels of sensory transmission are unaffected by cross-modal selective attention, but that longer latency exogenous and endogenous potentials are enhanced to stimuli in the attended modality. PMID- 2247551 TI - Event-related potential indices of selective attention and cortical lateralization in schizophrenia. AB - Auditory event-related potentials (ERPs) from a multidimensional selective attention task were recorded from 10 unmedicated schizophrenic patients and 10 age- and sex-matched healthy controls. Tone pip stimuli varying on the dimensions of pitch (high or low) and location (left or right ear) formed four 'channels' of stimuli: left low, left high, right low, and right high. The pitch difference was considerably more difficult to discriminate than the location difference. Subjects were instructed to pay attention to a designated channel and press a button whenever they detected a long-duration, rare target tone that occurred amongst frequent short-duration standard tones. There were a number of differences between unmedicated schizophrenics and controls in processing negativity elicited by standard tones. There was no evidence of hierarchical processing of stimulus dimensions in the early processing negativity component, and the late frontal component was virtually absent in schizophrenics. Furthermore, there was evidence that in schizophrenics the processing of the location dimension was delayed for standard tones having the same pitch as the target. The P300 component to attended target tones was substantially reduced in schizophrenics over parietal sites but there was no difference between the two groups over frontal sites. The results are interpreted in terms of multiple attentional deficits in schizophrenics that are indicative of a failure in the planning and execution of selective listening strategies. Such a failure may result from a dysfunction in the prefrontal regions of the brain. PMID- 2247552 TI - The effect of small variation of the frequent auditory stimulus on the event related brain potential to the infrequent stimulus. AB - We investigated whether the mismatch process between a rare stimulus and the trace of the frequent stimulus, which generates the mismatch-negativity component of the event-related potential, can tolerate a small variation in the intensity of the frequent stimulus. Series of short tone pips were presented to 10 subjects while they were reading a book and ignoring the auditory stimuli. The intensity (mean 80dB) of the frequent stimulus (600 Hz) varied within a range that was different in different blocks. The probability of the infrequent stimuli which were, in different blocks, either intensity deviants (600 Hz/70dB) or frequency deviants (650 Hz/80dB) was 10%. Both deviant stimuli elicited mismatch negativity even when the intensity of the frequent stimulus varied, although the amplitude of this component decreased with the increasing variability of the frequent stimulus. These results show that the generator process of mismatch negativity tolerates some variation in the repetitive stimulus, thus indicating that this process is also activated in ecologically more valid conditions. This is crucial to the interpretation of the generator process of mismatch negativity as a biologically vital warning mechanism. PMID- 2247553 TI - Issues in biometrics: offset potentials and the electrical stability of Ag/AgCl electrodes. AB - There has been a continuing interest in many areas of psychophysiological research in the quantification of slow wave bioelectric potentials recorded from the surface of the skin. However, surprisingly little research has focused specifically on methods for stabilizing and minimizing the offset potentials of the sintermetallic Ag/AgCl surface electrodes commonly used in such noninvasive bioelectric measurement. To provide empirically based recommendations in this regard, we contrasted the effects of three common storage methods (air dry vs. saline vs. carbon rod) on the two distinct types of Ag/AgCl surface electrodes (sintermetallic vs. electrolytic) under simulated experimental conditions. The obtained results confirm that minimum offset potentials and maximum stability for electrolytic Ag/AgCl electrodes are obtained when they are stored in a 0.9% NaCl solution with their leads shorted together and connected in parallel to a carbon rod partially immersed in the solution (cf. Cooper, 1956). In addition, the pattern of results suggested that the inter-session unshorted storage of sintermetallic electrodes in a mild saline solution is to be recommended over either shorted saline storage in parallel with a carbon rod or unshorted dry storage. PMID- 2247554 TI - The American Psychosomatic Society: why? PMID- 2247556 TI - Slow-reacting immunoglobulin in relation to social support and changes in job strain: a preliminary note. AB - Fifty working subjects in the ages 25 to 60 were asked to rate the amount of job strain (demands divided by decision latitude) that they experienced on four occasions at intervals of three to four months. Blood samples were taken for the analysis of immunoglobulin G before work started on these work days. After the end of the studied year each subject was asked to rate the total amount of social support that he/she had experienced. Both availability and adequacy of support were rated. The reported degree of job strain was unrelated to season and number of order of observation. Immunoglobulin G was observed to rise progressively with rising job strain. The reported adequacy of social support was negatively associated with immunoglobulin G--the more adequate the support was reported to be, the lower the immunoglobulin G level. This association was stronger at peak levels of job strain and became weak and nonsignificant at low levels of job strain. Thus, when job strain increased immunoglobulin G increased mainly among those with poor adequacy of social support. PMID- 2247555 TI - Psychological and neuroendocrine measures related to functional immune changes in anticipation of HIV-1 serostatus notification. AB - Our previous work indicated that gay males ultimately found to be seronegative showed impaired lymphocyte proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) upon entering a study in which they would be notified of their human immunodeficiency virus-Type 1 (HIV-1) antibody status. To examine the degree to which alterations in various neuroendocrine and psychological markers might be related to this phenomenon we measured plasma cortisol, beta endorphin, denial coping strategies, intrusive thoughts related to AIDS risk, and several affective distress markers in 46 HIV-1 seronegative subjects at each of the timepoints previously studied. Results indicated that cortisol levels were elevated at study entry and decreased across the subsequent five-week period- mirroring the changes in mitogen responsivity across these timepoints. Analyses of individual differences showed that higher baseline cortisol and lower denial coping scores predicted lower PHA values at baseline. Persisting intrusive thoughts about risk of HIV-1 infectivity (after seronegativity notification) were consistently associated with higher plasma cortisol levels. Finally, beta endorphin levels did not change significantly across the 10-week observation period, were not associated with psychological variables, and were inconsistently associated with immune functioning. PMID- 2247557 TI - Is allergic rhinitis more frequent in young adults with extreme shyness? A preliminary survey. AB - Previous studies suggest that social anxiety, allergies and distressed affect may be interrelated in some persons. For example, extremely introverted patients experience a poorer course and outcome of allergies as well as greater degrees of distressed affect such as depression and anxiety than do extraverts. Patients with affective disorders have a higher prevalence of atopic allergy than the general population; families of patients with panic disorder and major depression have the highest frequency of shy children. Preliminary investigation also indicate that behaviorally inhibited Caucasian children (initially shy and cautions in unfamiliar situations) and their families have more allergies, especially hay fever, than do uninhibited, socially outgoing children. The present survey evaluated the frequency of self-reported shyness. The most introverted subjects had significantly higher scores on self reports of depression, fearfulness, and fatigue, as well as a higher prevalence of hay fever. The data support the possibility of a distinct subgroup of shy individuals with concomitant vulnerability to specific allergies and affective disorders. PMID- 2247559 TI - The predictive role of psychosocial stress on symptom severity in premenstrual syndrome. AB - Twenty-five women with well defined, severe premenstrual syndrome (PMS) were studied prospectively during three consecutive menstrual cycles to examine the association between concurrent psychosocial stress and symptom severity. Stress, mood, physical symptoms, and urinary ovarian steroid metabolites were measured daily. Stress accounted for only 6% and 10% of the unique variance in physical symptom and mood scores, respectively, across the menstrual cycle. In individual woman, there was no association between the severity of symptoms and the cumulative daily stress reported during each cycle. We conclude that in this carefully screened population of women without coexisting psychiatric disorder, PMS symptom severity could not be determined by the amount of psychosocial stress. PMID- 2247558 TI - The effects of relaxation/imagery training on recurrent aphthous stomatitis: a preliminary study. AB - Recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa. Although etiology remains unknown, immunological and emotional disturbances have been implicated in the pathogenesis of RAS. No consistently effective therapeutic regimen has been found. The present study investigates the voluntary modulation of RAS employing hypnosis-like relaxation/imagery training procedures. A multiple baseline design was used to evaluate change in frequency of ulcer recurrence. The role of psychological distress, ratings of perceived pain, and hypnotizability in the treatment of RAS were also examined. Results suggest that the relaxation/imagery treatment program was associated with a significant decrease in the frequency of ulcer recurrence for all subjects. Psychological distress was examined for relationship to ulcer recurrence and symptomatic changes with treatment, but no pattern was found. Finally, little support was found for the role of high hypnotic ability in the treatment of RAS. PMID- 2247560 TI - Cultural variations in response to painful stimuli. AB - This review updates the literature on cultural differences in response to laboratory-induced pain. Thirteen studies were located, and there was great diversity among the investigations with regard to racial and ethnic groups studied, methods of pain induction, and experimental outcome. There appear to be no racial/ethnic differences in the ability to discriminate painful stimuli. More difficult to assess is cultural variation in the response to laboratory-induced pain. Age, sex, experimenter ethnicity and the subjects' working conditions may affect and confound the response to painful stimuli. Given these confounds, there is no consistent experimental evidence to suggest cultural differences in pain response. Perspectives derived from the social sciences may help future laboratory researchers better delineate cultural variations in the pain response. The difficulties inherent in the translation of pain descriptors across cultural boundaries make pain tolerance, rather than pain threshold, the more relevant transcultural pain measure. Since tremendous cultural heterogeneity can exist within one racial group and since even ethnic groups within a single racial category demonstrate variations in the response to pain, this field might now profitably focus on the study of ethnic group differences. Delineation of ethnic groups for study will require assessment of variations in intra-ethnic acculturation and assimilation which certainly affect group demarcation and may influence pain behavior. Specific guidelines are presented so that future experimental researchers may better operationalize culture in the laboratory setting. PMID- 2247561 TI - The relationships between dimensions of hostility and cardiovascular reactivity as a function of task characteristics. AB - The present study examined the independent relationships between dimensions of hostility and cardiovascular responses to a laboratory task with and without harassment. Fifty-three males, aged 18 to 26, with a negative parental history of cardiovascular disease were selected on the basis of their scores on the Cook and Medley Hostility (Ho) scale (greater than 24 or less than 14). Factor-analysis of six separate measures of hostility/anger resulted in a two-factor solution; Factor 1 representing antagonistic hostility and Factor 2 representing neurotic hostility. Results showed that high factor scores on antagonistic hostility were significantly associated with greater systolic blood pressure (SBP) and forearm blood flow (FBF) changes and poorer SBP recovery to harassment. In addition, high factor scores on neurotic hostility significantly predicted greater FBF changes to harassment. Additional correlational analysis showed that cardiovascular responses were positively associated with self-reported negative affects but only for subjects with high scores on either dimension. These results are in agreement with recent evidence suggesting that only antagonistic hostility may be related to increased severity of coronary artery disease and that the degree of interpersonal conflict moderates the association between coronary-prone behaviors and cardiovascular responses. PMID- 2247563 TI - Can psychotherapy prolong cancer survival? PMID- 2247562 TI - Gender differences in blood pressure control during a variety of behavioral stressors. AB - This study assessed gender differences in hemodynamic response patterns to behavioral stressors. In addition, the extent to which gender differences in cardiovascular reactivity were a function of the type of challenge was determined by employing tasks relying on stereotypically male areas of competence and a task relying on stereotypically female areas of competence. Sixteen female and 15 male graduate, medical or dental students were exposed to two speech tasks and two math tasks. While there were no significant differences in blood pressure reactivity between the genders, females exhibited significantly greater cardiac output increases across all tasks than males, while males tended to respond with greater increases in total peripheral resistance compared with females. Furthermore, during two of the tasks, significantly more females were classified as myocardial hyperreactors (based on increases in cardiac output), while significantly more males were vascular hyperreactors (based on increases in total peripheral resistance). A post hoc analysis also indicated an apparent association between oral contraceptive use and higher cardiovascular reactivity among the females tested. This association may have been a consequence of the decision to test all women during days 10 to 14 of the menstrual cycle when reactivity in women not using oral contraceptives may be suppressed. PMID- 2247564 TI - Methodology in consultation-liaison research: a classification of biases. AB - Methodology is receiving overdue attention in psychiatric research. This article focuses on biases encountered in studies in consultation-liaison psychiatry. A classification of biases derived from epidemiology is presented, and the expected impact of each bias is discussed. Methods to minimize bias in the design and implementation of consultation-liaison research are suggested. PMID- 2247565 TI - Psychotropic drug use in the medically ill: Part I. AB - Underlying medical illness and drug interactions may make the use of psychotropic agents in some physically ill patients problematic. This overview, published in two parts, discusses six major classes of psychotropic medications (cyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, neuroleptics, lithium, psychostimulants, and carbamazepine) and examines their use in the setting of specific types of medical illnesses (e.g., cardiovascular, pulmonary, hepatic, and renal disease). Practical considerations in using psychotropic medications in medical-surgical patients, particularly those who are elderly or medically debilitated, receive special emphasis. In part I, the use of cyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, and buspirone are discussed. PMID- 2247566 TI - Factitious disorders in a general hospital setting: clinical features and a review of the literature. AB - Factitious disorder is an uncommon, but probably underdiagnosed, condition associated with considerable morbidity, mortality, and health care expenditure. This diagnosis was made in 10 (0.8%) of 1,288 patients consecutively referred to the psychiatric consultation-liaison service of a tertiary-care general hospital. Seven of 10 identified cases were female. Associated psychiatric disturbances included substance use, psychogenic pain disorder, malingering, dysthymic disorder, and borderline personality disorder. Only two cases accepted ongoing psychotherapy. One death due to factitious behavior occurred during the brief period of follow-up. Greater awareness of this condition among primary caregivers is necessary in order to improve case identification and to reduce associated morbidity. PMID- 2247567 TI - Medical clearance: fact or fiction in the hospital emergency room. AB - Prior medical clearance is an important variable in the psychiatric assessment of the emergency room patient. An analysis of documentation of prior physical examinations on a consecutive series of 137 patients seen in a general hospital emergency room and referred for psychiatric consultation revealed wide variance in physical examinations. The authors discuss the implications of incomplete physical examinations for psychiatry and offer proposals for standardization of this important aspect of patient evaluation. PMID- 2247569 TI - Adjustment disorders in medically ill inpatients referred for consultation in a university hospital. AB - The study examined medical records of 121 medical-surgical inpatients diagnosed with adjustment disorder by psychiatric consultants in a university hospital. Medical illness was the primary stressor, evoking the maladaptive reaction in 83 (68.6%) cases. These patients were largely free of preceding psychiatric problems, suffering protracted hospitalizations for advanced illnesses, particularly malignancy and diabetes; in contrast, the 38 (31.4%) patients whose adjustment disorder was precipitated by a stressor other than medical illness had established psychiatric histories and recurrent problems with relationships or finances. The data suggest that in the medically ill, identifying the primary stressor producing an adjustment disorder is more instructive than focusing upon "predominant" symptomatology and "subtypes." PMID- 2247568 TI - Behavioral symptoms in cystic fibrosis vs. neurological patients. AB - In this study, the authors compared the adaptation of a group of patients with cystic fibrosis (CF) (N = 46; mean age = 10.91 years) to a similar group of patients who attended a neurological clinic (N = 71; mean age = 10.47). Both groups were assessed using the Child Behavior Checklist by Achenbach (parent version). CF patients demonstrated significantly less psychosocial morbidity than the neurological patients. This was true for overall behavioral symptoms, externalizing and internalizing symptoms, and social competence. The findings indicate better adaptation by the CF group and further support the literature indicating better adaptation in CF patients over other chronically ill groups. Possible reasons for such findings are discussed. PMID- 2247570 TI - Personality alterations in multi-infarct dementia. AB - Multi-infarct dementia (MID) produces changes in intellectual function and in overt behavior, but alterations in demeanor have received little systematic investigation. In this study, an assessment of personality change occurring after the onset of the dementia was performed using an inventory completed by the subjects' spouses. Personality alterations in MID were compared to those occurring in a group of healthy elderly individuals. Twelve of the 18 inventory items changed more in the MID patients than in normal control subjects. Personality changes are a consistent part of the clinical syndrome of MID and occur early in the course of the disease. PMID- 2247571 TI - Behavioral correlates and staff recognition of alcohol use in a university hospital trauma service. AB - Hospital course and admission blood alcohol levels were compared in 242 consecutive adult trauma admissions. A 33% overall intoxication rate was found. Intoxicated patients were more likely to be young, male, and Hispanic or black and to be involved in fights, stabbings, and automobile accidents in which they were presumed to be at fault. These patients were also more likely to manifest disruptive behavior in the emergency room. Disruptive behavior on the ward was not correlated with alcohol intoxication at admission, but was correlated with the history of head injury. Staff recognition of intoxication was high, but only about 7% of the patients who were intoxicated at admission were referred to alcohol treatment programs. More frequent referrals for such treatment might decrease trauma center admissions and the high costs associated with them. PMID- 2247572 TI - Medical students' attitudes toward AIDS, homosexual, and intravenous drug-abusing patients: a re-evaluation in New York City. AB - After completing their clinical rotations, 69% of the third-year medical school class at Columbia University responded to a survey based on one originally used by Kelly et al. at the University of Mississippi, to determine their attitudes toward acquired immunodeficiency syndrome (AIDS) patients, homosexual men, and intravenous drug abusers (IVDAs). Results of this study were compared to the findings of Kelly et al. to determine how, if at all, geographic and environmental exposures affected student attitudes. Unlike the University of Mississippi students, who exhibited a highly negative and prejudiced view of homosexuals and patients with AIDS, Columbia students displayed no evidence of negative attitude toward homosexuals and a much less harsh judgment of AIDS patients. They, however, did have dramatically negative attitudes toward IVDAs; 78.4% stated that they strongly disliked and would avoid this group of patients. There is a complex multi-variable environmental effect on students' attitudes during medical school. It is not possible to generalize attitudes from one medical school to another. The necessity of incorporating activities into student education to evaluate and to reduce prejudice is discussed. PMID- 2247573 TI - Diagnosing depression in patients with medical illness. PMID- 2247574 TI - Multidisciplinary approaches to consultation-liaison psychiatry: the C-L psychologist on an AIDS treatment team. PMID- 2247576 TI - Disabling urinary obsessions: an uncommon variant of obsessive-compulsive disorder. PMID- 2247575 TI - Neurosyphilis and organic mood syndrome: a forgotten diagnosis. PMID- 2247577 TI - Protracted ventricular arrhythmias occurring after abrupt tricyclic antidepressant withdrawal. PMID- 2247578 TI - Medical board president: another role for the consultation-liaison psychiatrist. PMID- 2247579 TI - Stuttering after a dystonic reaction. PMID- 2247580 TI - The use of ECT for Parkinson symptoms in a nondepressed patient. PMID- 2247581 TI - On improving psychiatric consultation to nonpsychiatrist physicians. PMID- 2247583 TI - The wheel turns full circle or back to the beginning? PMID- 2247582 TI - On dysmorphophobia misdiagnosed as obsessive-compulsive disorder. PMID- 2247584 TI - Patterns of behaviour amongst injecting drug users--implications for HIV. AB - HIV-related behaviour was studied in a sample of 187 injecting drug users in Stockport, most of whom were not regular users of health services. 174 of the group had shared needles, most of them within the last 4 weeks. Among the 174, more than a quarter were under 20 years of age; most had had multiple sexual partners, and only a minority ever used condoms. Most perceived themselves to be at low or no risk of HIV infection. Perception of risk was related to changes in reported sexual behaviour, but not to needle-sharing. Implications for existing control programmes are considered. PMID- 2247585 TI - The use of personal cassette players among youths and its effects on hearing. AB - To assess the prevalence of use of Personal Cassette Players (PCP) among youths in a residential community in Hong Kong, we interviewed 487 youths aged 15-24 years who attended various activities in eight Youth Centres in Shatin, Hong Kong. 394 (81%) reported using the Personal Cassette Player regularly. The mean duration of PCP use was 2.8 years with a median of 2 years. The mean time of listening to PCP was 4.5 hours per week. We further examined 124 subjects by otoscopy and of the 103 otoscopically normal individuals, audiometric tests were performed. Among the 78 PCP users and 25 non-users, no significant difference in the mean hearing threshold was observed for the frequencies tested. The mean ear canal sound level was 70.4 dBA. Four subjects were habitually exposed to sound levels higher than 85 dBA. One was exposed to 116 dBA and was found to have a 4000 Hz dip on his audiogram, suggestive of noise-induced hearing loss. In general, despite the high prevalence of PCP use, most youths used their PCP at relatively safe sound levels with low risk of hearing loss. However, education directed towards the youth with respect to the potential hazard on hearing due to improper and prolonged use of PCP is still warranted. PMID- 2247586 TI - HBV infection among pre-school children in Naples (Italy) and the role of intrafamily contact. AB - In the Neapolitan area the prevalence of adult HBsAg carriers ranges from 4-7%. Moreover, hepatitis B virus (HBV) is responsible for most of the chronic hepatitis cases in childhood. Since the chronic carrier state in our area is acquired by early horizontal contact, we investigated the prevalence of HBV infection among 207 pre-school children and of HBsAg carriers among their family members. None of the children was found to be HBsAg positive and 3.9% of them had anti-HBs. HBsAg was positive in 29 out of 892 (3.3%) of the family members. There was a clear age-related distribution of the carriers, their prevalence reaching 6.7% among the elderly members. On the whole, 19 out of the 207 index cases had at least one HBsAg carrier in their family. The results suggest that in our area a decline of HBV endemia may be under way and that early intrafamily contact is no more a common pathway in acquiring an HBsAg carrier state. PMID- 2247587 TI - The incidence and correlates of health-related behavioural change in a small Scottish community. AB - This paper reports on a survey of health related behavioural change in a small Scottish town. Four types of behaviour were surveyed; smoking, alcohol use, dietary habits and exercise. The results indicate that for both smoking exercise behavioural change is very unstable. Cutting down or giving up alcohol was significantly associated with cessation of smoking in women but not in men. All dietary changes were strongly inter-related. Giving up smoking, taking exercise and eating more fibre were significantly associated with very good reported health. Sex, age and social class patterns in health-related changes were evident. PMID- 2247588 TI - A survey of cigarette smoking among middle school students in 1988. AB - A survey of the prevalence of smoking in middle school students aged 13-21 years in Harbin city, China, was undertaken in the Spring of 1988. A random sample of 4712 students was selected using proportional stratified clustering. A self administered confidential questionnaire relating to smoking habits and certain family and school factors was administered. The results showed that 1.29% of the students (2.21% boys and 0.38% girls) smoked regularly, 5.62% (10.52% boys and 0.76% girls) were light smokers and 13.77% (24.29% boys and 2.92% girls) smoked only occasionally. Smoking habits were related to the type of school and to age, there being a higher proportion of smoking in senior grade students. Students were significantly more likely to smoke if they were male and if their siblings smoked. Prevalence of regular smoking was not related to parental occupation or family income. It is suggested that anti-smoking education in the school curriculum should be directed towards students in middle school. PMID- 2247589 TI - Modifiable risks for cardiovascular disease among general practitioners in Wales. AB - A random cluster sample of 520 general practitioners in Wales was invited to complete a postal questionnaire providing information on personal health status, and practice organisation and activities relating to the prevention of cardiovascular disease. Survey participants were also asked to provide a blood sample together with details of independently measured height, weight and blood pressure. 310 (60%) provided usable information and 280 (54%) provided blood samples. General practitioners in the study generally had better lifestyles and fewer coronary risk factors than the general population in Wales. Only 17% (43/251) of males were regular smokers, and 56% (134/239) of males and 32% (18/68) of females regularly take exercise. Few and uncontrolled elevated blood pressure. However, 39% (97/248) of males and 29% (15/52) of female GPs were overweight, and more than 40% (19/42) of male GPs aged 40-64 had cholesterol levels above 6.5 mmol. Six per cent (6/99) of male GPs aged 40-54 consumed greater than 35 units of alcohol each week. It is suggested that GPs have responded well to the challenges of reducing smoking among themselves and their patients, but that they have yet to recognise fully the risks to personal health associated with elevated cholesterol levels and high alcohol consumption. PMID- 2247590 TI - Cultural differences in a family planning clinic. AB - An analysis of the use of contraception in a multi-racial family planning clinic in relation to age, parity and ethnicity (Asian or non-Asian) was carried out in the London Borough of Newham. Whether follow-up appointments were given and kept and the taking of cervical smears were noted. Asian patients favoured the sheath (44%) and the IUD (31%); the Pill was less used at 20% with the cap little used at 3%. Non-Asian patients favoured the Pill (50%), and IUD (22%) with the sheath being used by 15% and the cap by 13%. Parity increased with age in both groups. The 16-20-year-old Asian patients chose the Pill (54%) in preference to the sheath (27%) whereas the older Asian patients chose the sheath in preference to all other methods. When follow-up appointments were given the failure rate was equal in both groups. 29% of the Asian patients had a cervical smear taken as against 45% of the non-Asian patients. PMID- 2247591 TI - The fragmentation of 670A MeV neon-20 as a function of depth in water. II. One generation transport theory. AB - The results of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses were compared with a "first principles" transport calculation in the straight-ahead approximation. This calculation assumes that the nuclear interactions of the incident particles lead to a secondary particle with the velocity of the incident projectile at the interaction point moving in the direction of the incident projectile. Subsequent nuclear interactions of the fragments were taken into account partially, by calculating the nuclear attenuation of the fragments in the residual material, but were not taken into account as a source of further nuclear interaction products. Fluence spectra were calculated per unit incident neon fluence for 14 absorber thicknesses. The acceptance for each fragment was calculated based on a knowledge of the material in the beam and of the beam extraction energy. The theoretical spectra were multiplied by the calculated acceptance and convoluted with the LET resolution associated with the experiment. The stopping power used in the transport calculation was found to predict a range approximately 1.6% shorter than that given by experiment; this small difference resulted in significant discrepancies between theory and experiment in the stopping region. For particles not stopping in the absorber, the transport calculation was accurate to within 30% for depths less than approximately 15 cm; the effects of tertiary particles become significant at greater depth. PMID- 2247592 TI - Characterization of a monoclonal antibody to thymidine glycol monophosphate. AB - A monoclonal antibody specific for thymine glycol (TG) in irradiated or OsO4 treated DNA was obtained by immunizing with thymidine glycol monophosphate (TMP glycol) conjugated to bovine serum albumin by a carbodiimide procedure. Screening by dot-immunobinding and enzyme-linked immunosorbant assay (ELISA) procedures gave eight clones that bound OsO4- treated DNA. One of them, 2.6F.6B.6C, an IgG2a kappa, was characterized further. Hapten inhibition studies with OsO4-treated DNA showed that the antibody was specific for TMP-glycol. Among the various inhibitors tested, inhibition was in the order TMP-glycol greater than 5,6 dihydrothymidine phosphate greater than TMP greater than thymidine glycol greater than TG. Inhibition by 5,6-dihydrothymidine, thymidine, thymine, AMP, and CMP was negligible. In OsO4-treated DNA, as few as 0.5 TG per 10,000 bp were detectable by direct ELISA. Inhibition assays could detect as few as 1.5 TG per 10,000 bp. The antibody was equally reactive with native or denatured DNA containing TG. Among the X-irradiated homopolymers dC, dA, dG, and dT, only dT reacted with the antibody. Using an ELISA, the antibody could detect damage in irradiated DNA at the level of 20 Gy. Thus the antibody is of potential use in assays for DNA damage caused by X rays or other agents that damage DNA by free radical interactions. PMID- 2247593 TI - Investigation of the repair of single-strand breaks in human DNA using alkaline gel electrophoresis. AB - Unstimulated lymphocytes from eight healthy persons were exposed to 10-, 30-, and 100-Gy doses of 60Co gamma radiation. The repair of damaged DNA was measured by (1) alkaline gel electrophoresis (extracted DNA loaded on 0.25% agarose gel, run at 1 V/cm for 39-44 h) at 0, 1, and 2 h after exposure and (2) incorporation of [3H]thymidine into unstimulated lymphocytes in the presence of 2 mM hydroxyurea 1 and 2 h after exposure. Both methods--alkaline gel electrophoresis and thymidine incorporation--showed that repair was completed within 2 h. PMID- 2247594 TI - Effect of step-down heating on brachytherapy in a murine tumor system. AB - The effects of step-down heating combined with low-dose-rate irradiation (brachytherapy) were studied using a murine mammary adenocarcinoma (MTG-B) grown in the flanks of C3H mice. Treatment was initiated when tumors reached 0.9 to 1.1 cm in diameter. Step-down heating consisted of 7.5 min at 45 degrees C immediately followed by 7.5 min at 42 degrees C. Step-up heating consisted of 7.5 min at 42 degrees C immediately followed by 7.5 min at 45 degrees C. Step-down heating and step-up heating were compared to a single 45 degrees C, 15-min hyperthermia treatment. These hyperthermia protocols were combined before, in the middle of, or after brachytherapy. There were 4 untreated controls, 6 sham controls, and 11 treated animals in each of the brachytherapy-alone and combined treatment groups. The entire experiment was repeated at brachytherapy doses of 988, 1273, and 1603 cGy. In addition, the effects of step-down heating, step-up heating, and single-temperature hyperthermia were tested alone and in combination with sham treatment for each sequence. Based on daily measurements of tumor diameter, the growth delay to doubling volume was used as the biological end point. To compare the various treatment protocols, an isoeffect thermal enhancement ratio (TERiso) was calculated. Step-down heating after 988 cGy brachytherapy had a TERiso of 2.0 +/- 0.04, while step-up heating after 988 cGy brachytherapy had a TERiso of 1.7 +/- 0.05. Overall, the thermal enhancement ratios calculated from these growth delays indicate that step-down heating caused significantly greater hyperthermic radiosensitization than step-up heating when combined with brachytherapy. PMID- 2247595 TI - Lung lavage therapy to lessen the biological effects of inhaled 144Ce in dogs. AB - To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 days for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles. PMID- 2247596 TI - Noninvolvement of the heat-induced increase in the concentration of intracellular free Ca2+ in killing by heat and induction of thermotolerance. AB - Mouse C3H 10T1/2 cells exhibited a two- to threefold increase in the concentration of free Ca2+ during heating at 45 degrees C. The increase was maximal for a heat dose which was still in the shoulder region of the survival curve. The increase was fully reversible in heat-sterilized cells. By changing the concentration of extracellular Ca2+, it was possible to modulate the concentration of intracellular free Ca2+ in heated cells. Lowering the extracellular concentration to 0.03 mM reduced the baseline concentration of intracellular free Ca2+, and prevented it from increasing in heated cells to a level exceeding that of nonheated cells incubated in medium containing 2.0 or 5.0 mM Ca2+. Raising the concentration of extracellular Ca2+ to 15.0 mM raised the baseline, and resulted in a heat-induced increase in free Ca2+ which was twofold higher than that of cells heated in medium containing 2.0 or 5.0 mM Ca2+. An elevated concentration of intracellular free Ca2+ during and after heating did not potentiate thermal killing, nor did a reduced concentration during and after heating mitigate killing. Furthermore, the data argue against a heat-induced increase in free Ca2+ to some threshold level, which potentiates cell killing by some other parameter. In addition, cells heat-shocked in either 0.03 or 5.0 mM extracellular Ca2+, and then incubated in the same concentration for 12 h at 37 degrees C, developed quantitatively similar amounts of tolerance to a second heating. The data suggest that the concentration of intracellular free Ca2+ does not play a critical role in thermal killing or the induction and development of thermotolerance. PMID- 2247597 TI - Effects of hydralazine on the blood flow in RIF-1 tumors and normal tissues of mice. AB - Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined. PMID- 2247598 TI - Differential modulation of specific gene expression following high- and low-LET radiations. AB - Experiments were designed to examine the effects of radiation quality on specific gene expression within the first 3 h following radiation exposure in Syrian hamster embryo (SHE) cells. Preliminary work demonstrated the induction of c-fos and alpha-interferon genes following exposure to low-linear-energy-transfer (low LET) radiations (X rays or gamma rays). More detailed experiments revealed induction of c-fos mRNA within the first 3 h following exposure to either X rays (75 cGy) or gamma rays (90 cGy). We could not detect induction of c-fos following exposure of SHE cells to fission-spectrum neutrons (high-LET) from the JANUS reactor administered at either high (12 cGy/min) or low (0.5 cGy/min) dose rates. Expression of alpha-interferon mRNA was similarly induced by low-LET radiations but only modestly by JANUS neutrons. The induction by gamma rays was dose dependent, while induction by neutrons was specific for low doses and low dose rates. These experiments demonstrate the differential gene inductive response of cells following exposure to high- and low-LET radiations. These experiments suggest that these different qualities of ionizing radiation may have different mechanisms for inducing many of the cellular consequences of radiation exposure, such as cell survival and cell transformation. PMID- 2247599 TI - Biological consequence of nuclear versus cytoplasmic decays of 125I: cysteamine as a radioprotector against Auger cascades in vivo. AB - When the radionuclide 125I is localized in mouse testis as 125I-iododeoxyuridine (an analogue of thymidine) and incorporated into the DNA of spermatogonial cells, the cytocidal effects are as severe as those due to densely ionizing alpha particles. In contrast, 125I confined to the cytoplasm of these cells is much less radiotoxic, the efficacy being the same as for selective irradiation of the testis with sparsely ionizing external X rays. The biological effects, in both cases, are strongly mitigated upon pretreatment of the testes with very small amounts (0.75 microgram) of cysteamine, a radioprotector. These findings suggest an important role for such chemical agents in radiation protection and in understanding the mechanisms of radiation damage involving radionuclides incorporated in tissue. PMID- 2247600 TI - A model of cell killing by low-dose-rate radiation including repair of sublethal damage, G2 block, and cell division. AB - A computer model that simulates the killing of exponentially growing cells by low dose-rate radiation is described. The model incorporates cell killing by single hit damage and double-hit (sublethal) damage, as well as repair of sublethal damage, delay of cell cycle progression, blockage and increased sensitivity of cells in the G2 phase of the cell cycle, and cell division. Seven cellular parameters determine the rate of cell killing. Initial estimates of most of these parameters can be made from independent experiments. Parameters were obtained that gave the best fit to the data for four cell lines, using constant or variable dose rates, and using as end points either the fraction of single cells forming colonies or the total number of clonogenic cells in a mass culture. Some of the parameters were determined to be insignificant or similar for the four cell lines. The main differences between the cell lines in patterns of cell killing over a range of dose rates appeared to be determined by differences in the values of four of the parameters. PMID- 2247601 TI - Radiation response of drug-resistant variants of a human breast cancer cell line: the effect of glutathione depletion. AB - Two drug-resistant variants of the human breast cancer cell line MCF-7 have been shown previously to exhibit radiation resistance associated with an increase in the size of the shoulder on the radiation survival curve. In the present study, glutathione (GSH) depletion was achieved by exposure of cells to buthionine sulfoximine (BSO) with, in some cases, additional treatment with dimethyl fumarate. Levels of GSH in the adriamycin-resistant subline MCF-7 ADRR are initially lower than in the other two sublines and are depleted to a greater extent by exposure to BSO. Wild-type MCF-7 cells are not sensitized by GSH depletion when irradiated under aerated conditions but are sensitized under hypoxic conditions to an extent which is related to the level of GSH depletion. In contrast both the drug-resistant sublines (MCF-7 ADRR and the melphalan resistant line MCF-7 MLNR) are radiosensitized by GSH depletion under both aerated and hypoxic conditions. It is hypothesized that in the case of the MCF-7 ADRR cell line, which expresses high levels of the GSH-associated redox enzyme systems, GSH-S-transferase and GSH-peroxidase (GSH-Px), radiosensitization results when GSH-Px is inhibited in GSH-depleted cells. The reasons for radiosensitization of aerated MCF-7 MLNR cells cannot be explained on this basis, however, and other factors are being examined. PMID- 2247602 TI - Incorporating dose-rate effects in Markov radiation cell survival models. AB - Markov models for the survival of cells subjected to ionizing radiation take stochastic fluctuations into account more systematically than do non-Markov counterparts. Albright's Markov RMR (repair-misrepair) model (Radiat. Res. 118, 1 20, 1989) and Curtis's Markov LPL (lethal-potentially lethal) model [in Quantitative Mathematical Models in Radiation Biology (J. Kiefer, Ed.), pp. 127 146. Springer, New York, 1989], which assume acute irradiation, are here generalized to finite dose rates. Instead of treating irradiation as an instantaneous event we introduce an irradiation period T and analyze processes during the interval T as well as afterward. Albright's RMR transition matrix is used throughout for computing the time development of repair and misrepair. During irradiation an additional matrix is added to describe the evolving radiation damage. Albright's and Curtis's Markov models are recovered as limiting cases by taking T----0 with total dose fixed; the opposite limit, of low dose rates, is also analyzed. Deviations from Poisson behavior in the statistical distributions of lesions are calculated. Other continuous-time Markov chain models ("compartmental models") are discussed briefly, for example, models which incorporate cell proliferation and saturable repair models. It is found that for low dose rates the Markov RMR and LPL models give lower survivals compared to the original non-Markov versions. For acute irradiation and high doses, the Markov models predict higher survivals. In general, theoretical extrapolations which neglect some random fluctuations have a systematic bias toward overoptimism when damage to irradiated tumors is compared with damage to surrounding tissues. PMID- 2247603 TI - Age-related susceptibility of mouse liver to induction of tumors by neutrons. AB - The induction of liver tumors has been studied in BC3F1 male mice after acute whole-body irradiation with fission neutrons and X rays, given at different ages. In prenatally irradiated mice, a small effect is seen after doses of 0.3 to 2.1 Gy of X rays, and a more pronounced effect is found after neutron doses of 0.09 to 0.62 Gy. At 3 months of age the animals show a higher incidence after X-ray doses from 2 Gy, and for neutrons from 0.17 Gy. At 19 months of age, liver tumors are rarely induced by either type of radiation. These findings are confirmed by the statistical analysis of trend. The possibility of deriving dose-response relationships for liver tumors was also investigated. In the dose ranges where the risk appears to increase as a function of the increase in dose, the data points for neutrons were well fitted by a linear expression. A pure quadratic relationship best fitted the X-ray data. Using these expressions, the RBE for neutrons was 28 at 0.09 Gy for prenatal irradiation and 13 at 0.17 Gy for irradiation at 3 months. This suggests the existence of a risk of developing liver tumors after exposure to radiation, and fetal liver seems to be particularly sensitive to neoplastic transformation. This risk may be negligible at low doses (less than 1 Gy) of low-LET radiation, or with exposure at older ages. PMID- 2247604 TI - Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats. AB - Pregnant rats were exposed to gamma radiation from a 137Cs irradiator on gestational Day 15. Fetuses that received 0.25, 0.5, 0.75, or 1.0 Gy were examined 24 h after irradiation for changes in the cells of the cerebral mantle of the developing brain. The extent of changes following 0.5 Gy was studied at 3, 6, 12, or 24 h after exposure. Cortical thickness of the cerebral mantle was not significantly altered. The number of pyknotic cells, number of macrophages, nuclear area, and number of mitotic cells were altered in a dose-related way. The number of pyknotic cells was significantly increased at all doses. A positive correlation between the number of pyknotic cells and the number of macrophages developed with time. At 3 h after irradiation about 60% of pyknotic cells were found in the subventricular zone and about 25% in the intermediate zone and cortical plate. The number of such cells in the upper layers of the cortex steadily increased up to 24 h, at which time about 70% of pyknotic cells were in these two layers. The relationship of the movement of pyknotic cells to migration of postmitotic neuroblasts is discussed. PMID- 2247605 TI - Spontaneous DNA damage and its significance for the "negligible dose" controversy in radiation protection. PMID- 2247606 TI - Mitochondrial aminoacyl-tRNA synthetases. PMID- 2247607 TI - Ribosomal frameshifting from -2 to +50 nucleotides. PMID- 2247608 TI - Inaccuracy and the recognition of tRNA. PMID- 2247609 TI - Ribonucleases, tRNA nucleotidyltransferase, and the 3' processing of tRNA. PMID- 2247610 TI - The numerous modified nucleotides in eukaryotic ribosomal RNA. PMID- 2247611 TI - Damage to DNA and chromatin structure from ionizing radiations, and the radiation sensitivities of mammalian cells. PMID- 2247612 TI - A tale of two enzymes, deoxycytidylate deaminase and thymidylate synthase. PMID- 2247613 TI - Stable DNA loops in vivo and in vitro: roles in gene regulation at a distance and in biophysical characterization of DNA. PMID- 2247614 TI - The levels of prostaglandins associated with the reproductive cycle of the scallop, Patinopecten yessoensis. AB - The present experiment was undertaken to investigate the seasonal variations of levels of prostaglandins (PGs) and regulation of these levels in the ovary and hemolymph of the scallop. The levels of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) in the hemolymph and ovary increased during sexual maturation, and these levels in the ovary showed a marked increase in the spawning season. Consecutive administration of antiestrogen inhibited the increase of the levels of PGF2 alpha and PGE2 during sexual maturation. These results indicate that the seasonal variations of the levels of PGF2 alpha and PGE2 are closely related to the reproductive cycle, suggesting that PGF2 alpha and PGE2 may be involved in the sexual maturation and spawning of the scallop. Furthermore, it was supposed that estrogen likely plays a role in the regulation of PGs production in female, well known in mammals. PMID- 2247615 TI - Cocaine use and its effect on umbilical artery prostacyclin production. AB - Cocaine's association with adverse perinatal outcome has been attributed to its inhibition of norepinephrine uptake. This study examined the effect of cocaine on umbilical artery prostacyclin (PGI2) production. Umbilical arteries from pregnant cocaine users and controls were incubated in vitro and PGI2 levels in the media determined by measuring its stable metabolite, 6-keto-PGF1 alpha, by RIA. Cocaine users showed a significant decrease (p less than .05) in PGI2 production from their umbilical arteries when compared to controls. This appears to be through a direct effect of cocaine, as it decreases PGI2 production when added in vitro to umbilical arteries from controls. In addition, in vitro phospholipase A2 activity is inhibited by cocaine in a dose-dependent manner. These results suggest that the adverse perinatal outcome associated with cocaine use may be due in part to reduced vascular PGI2 production in the fetus. PMID- 2247617 TI - Effect of pregnancy-specific protein B on prostaglandin F2 alpha and prostaglandin E2 release by day 16-perifused bovine endometrial tissue. AB - Five normal estrous cycling multiparous non-lactating Brahman cows were utilized to determine if pregnancy-specific protein B (PSPB) would alter prostaglandin F2 alpha (PGF) and prostaglandin E2 (PGE) synthesis/release by endometrial tissue. The uterine horn ipsilateral to the corpus luteum was excised on Day 16 of the estrous cycle. Endometrial tissue (200 mg wet wt) was cultured in Nutrient Mixture F-10 medium in a perifusion system. The tissue and medium were aerated with 95% O2: 5% CO2 and temperature was maintained at 39 degrees C. The medium flow rate was 100 microliters/min and fractions were collected at 20 min intervals. After a 120 min settling period, tissue culture continued with: 1) control (medium only); 2) 2 micrograms [Asu1,6]-oxytocin/ml medium for 1 h; 3) 4 or 8 micrograms PSPB/ml medium for 2 h; or 4) 4 or 8 micrograms PSPB/ml medium for 2 h plus 2 micrograms oxytocin/ml medium during the second h. Differences in PGF and PGE secretion rate were not found between 4 and 8 micrograms PSPB. Therefore, groups were combined and data were analyzed according to tissue not receiving PSPB (control); receiving PSPB and receiving PSPB plus oxytocin. A nonsignificant rise (p greater than 0.10) in PGF secretion was observed in response to PSPB and PSPB plus oxytocin above the control by the end of the perifusion period (263.7 +/- 41.7, 220.0 +/- 41.7 and 166.1 +/- 41.7 pg/(100 mg tissue/min), respectively). Treatment with PSPB alone elevated (p less than 0.05) PGE secretion rate above control by 100 and 160 min post-removal of PSPB treatment. Treatment with PSPB plus oxytocin elevated (p less than 0.05) PGE release above control by 20 min after starting oxytocin treatment and continued throughout the duration of the perifusion. Pregnancy-specific protein B plus oxytocin-induced PGE release was greater (p less than 0.05) than PSPB alone after initiating the oxytocin treatment until 20 min after removal of the treatments. However, no further differences between PSPB alone and PSPB plus oxytocin treatments were detected throughout the remainder of the perifusion period. It appears that PSPB tends to elevate PGF release and significantly elevates PGE release from Day 16 endometrial tissue. PMID- 2247616 TI - Effects of the protein kinase inhibitors, staurosporine and K-252a, on PGI2 production by rat liver cells (the C-9 cell line). AB - Staurosporine and K-252a, known inhibitors of several protein kinases, stimulated PGI2 production (measured as 6-keto-PGF1 alpha) in rat liver cells (the C-9 cell line). Preincubation of the rat liver cells with staurosporine or K-252a enhanced the PGI2 production stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), platelet activating factor (PAF) and the Ca2(+)-ionophore A-23187, but not the PGI2 synthesis stimulated by exogenous arachidonic acid. These results suggest that phosphorylation of some proteins or certain amino acids on a protein can regulate arachidonic acid metabolism probably in the pathway leading to deesterification of phospholipids. PMID- 2247618 TI - Synthesis of a deuterated analogue and development of antibody/GC/MS for the determination of nocloprost in plasma. AB - An analytical method for the determination of the PGE derivative nocloprost in plasma was developed combining the features of both radioimmunoassay and GC/MS. The antibody usually employed in nocloprost radioimmunoassay was coupled to Sepharose 4B and used as a stationary phase for the extraction of the drug. After appropriate derivatisation, nocloprost was determined by GC/MS in the negative ion-chemical ionisation mode. As an internal standard deuterated nocloprost was synthesized and added to the plasma samples before extraction. The extraction recovery was 94% and the limit of detection was 5 pg/ml. Intra- and interassay precision at 100 pg/ml was calculated as 3.3 and 4.0%, respectively. PMID- 2247620 TI - The modulation of prostaglandin synthesis by peritoneal fluids. AB - Biological fluids from several sources (e.g. blood, fetal urine, amniotic fluid) have been shown to contain factors that modulate prostaglandin (PG) synthesis. In this study, we investigated the possibility that peritoneal fluid contains substances that may regulate PG synthesis. Peritoneal fluids were obtained from women undergoing diagnostic laparoscopy for infertility. Fluids from women without evident pelvic pathology were incubated with prostaglandin synthase prepared from bull seminal vesicles in the presence of excess arachidonic acid, and the production of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was quantified by specific radioimmunoassay. The untreated fluids inhibited potently the synthesis of PGE2 but such inhibitory activity was not extractable by chloroform:methanol. An ultrafiltrate of the fluid containing molecules smaller than 10,000 Daltons stimulated PGF2 alpha synthesis but this activity was also lost after extraction. The extracted fluid did, however, stimulate the synthesis of prostacyclin (as reflected by 6-keto-PGF1 alpha). PMID- 2247619 TI - Enzyme immunoassay measurement of the urinary metabolites of thromboxane A2 and prostacyclin. AB - We have used a recently developed enzyme immunoassay (EIA) method for measuring urinary concentrations of TXB2, 6-keto PGF1 alpha, 2,3-dinor-TXB2, 2,3-dinor-6 keto PGF1 alpha and 11-dehydro-TXB2 using acetylcholinesterase from Electrophorus Electricus coupled to TXB2, 6-keto PGF1 alpha and 11-dehydro-TXB2. Urinary PGI2 and TXA2 breakdown products and their metabolites were extracted from 3-40 ml of urine corresponding to 100 mumoles creatinine. Measurements were performed after Sep-Pak extraction and thin layer chromatography separation in a system that allows separation between dinor- and parent derivatives. Because of the relatively high cross reactivity (10-15%) of the anti-TXB2 serum with 2,3-dinor TXB2 and the anti-6-keto PGF1 alpha serum with 2,3-dinor-6-keto PGF1 alpha, measurements were done using 3 antisera (anti-TXB2 and anti-6-keto PGF1 alpha diluted 1/50,000, anti 11-dehydro-TXB2 diluted 1/200,000). The reproducibility of the technique was assessed by measuring the same urine stored frozen in aliquots together with each series of samples (Coefficient of variation 6-12% (n = 20), depending on the compound). In addition, the use of a different solvent system for the thin layer chromatography did not affect the results although the migration of the compounds was modified significantly. Determination of the urinary excretion of TXB2 and prostacyclin metabolites in 17 healthy individuals by this method provided results in agreement with those obtained by other methodologies. In addition, comparisons made between EIA and gas chromatography/mass spectrometry analysis showed good correlation between the urinary metabolites as determined by each technique (r = 0.98). PMID- 2247622 TI - A dose distribution evaluation utilizing megavoltage CT imaging system. AB - An isodose distribution (collision kinetic energy distribution) was acquired using a megavoltage CT imaging system. Direct comparison of dose distributions has become important for verification in innovative treatment techniques. Three dimensional implementation of this system is considered highly feasible. PMID- 2247621 TI - Local hyperthermia combined with radiotherapy, chemotherapy, or arterial chemoembolization. AB - Local hyperthermia combined with radiotherapy, chemotherapy, or arterial chemoembolization was performed in 31 patients with malignant tumors using an HTM 3000 heater. The response rate was 41.9%. Fifteen patients with superficial tumors had a high rate of response (60%). Response was particularly good (75%) when radiotherapy was also used. In contrast, the response rate was low (25%) in 16 patients with deep seated tumors. However, the criteria for assessment might not be appropriate. If improvement in symptoms and intratumorous changes were also considered, the therapy was judged to be valuable in 56.3% of the patients. No adverse reactions of concern developed except in some special cases. Hyperthermia with the HTM 3000 heater was safe. PMID- 2247624 TI - Uptake of technetium-99m DTPA in retroperitoneal liposarcoma. AB - 99mTc-DTPA, a renal agent, has been noted to accumulate in tumors such as neurofibroma, uterine myoma, soft tissue sarcoma, hepatic hemangioma, leiomyosarcoma, and plasmacytoma. We report a case in which uptake of 99mTc-DTPA was demonstrated in a retroperitoneal liposarcoma. PMID- 2247623 TI - Clinical application of DSA and evaluation of its methods: analysis of 160 cases and review of literature. AB - A total of 160 patients of two hospitals received 192 DSA examinations with different contrast administrations, and techniques of performing DSA were analyzed, compared, and evaluated with reference to the literature. It was concluded that (1) the peripheral injection of contrast material for IVDSA via cannula is simpler than that via a short catheter, but the incidences of contrast extravasation in both cases are higher than with central injection. (2) Both the lower part of the superior vena cava and the right atrial cavity are safe sites for central injection. With central injection for IVDSA, the arterial iodine concentration is approximately double that of peripheral injection, and consistent high quality examinations of the intracranial vessels may be obtained. However, neither peripheral nor central injections can visualize the small vessels clearly. (3) IVDSA may be substituted for conventional angiography only in examinations of the aorta and its main branches. (4) IADSA is becoming a superior angiographic technique and its clinical application is increasing. In addition, means of avoiding contrast extravasation during IVDSA and the main points of selecting the optimal technique for DSA are described in this paper. PMID- 2247625 TI - Evaluation of MRI in moyamoya disease. AB - We present the MRI findings of six patients with angiographically documented moyamoya disease. All patients underwent CT and MRI, and MRI findings were compared with those of CT. In two patients both preoperative and postoperative MRI were performed. Most of the abnormalities secondary to moyamoya disease were clearly identified on MRI, which proved to be superior to CT, and it was revealed that the effectiveness of surgery as well as the severity of the disease could also be evaluated successfully by this powerful technique. PMID- 2247626 TI - CT diagnosis of retrocaval ureter associated with double inferior vena cava: report of a case. AB - A case of retrocaval ureter associated with double inferior vena cava, an exceedingly rare venous anomaly, is reported. This anomaly was correctly diagnosed by CT. CT after intravenous contrast injection showed the double inferior vena cavae on both sides of the abdominal aorta and the right ureter crossing the right inferior vena cava posteriorly. CT is a good diagnostic modality with which to demonstrate such a vascular anomaly, and the clinical usefulness of CT is stressed. PMID- 2247628 TI - Proceedings of the International Meeting on Physical, Biological and Clinical Aspects of Total Body Irradiation. The Hague, The Netherlands, 7-9 September, 1988. PMID- 2247627 TI - Fogging effect and MR imaging: a case report of pontine infarction. AB - We used serial MR imaging to examine a pontine infarct in an aged man. The fogging effect was observed on the images obtained 12 days after ictus. Knowledge of the fogging effect is important for a correct interpretation of MR imaging. PMID- 2247629 TI - Techniques applied for total body irradiation. AB - In this review, different techniques of total body irradiation are discussed with special attention to their advantages and disadvantages. The results of an EBMT questionnaire, which was sent out to the European TBI centres, are also presented. It turned out that there exists a great variety in techniques, total doses, and fractionation schedules used all over Europe. It was also clear that the documentation concerning dosimetry and the time factor in TBI still has some deficiencies. Therefore, a proposal is now made for reporting the technical and dosimetric aspects used in total body irradiation in an unambiguous manner. PMID- 2247630 TI - Chemo-radiotherapy and autologous bone marrow transplantation in poor prognosis neuroblastoma. AB - In Genoa, 39 patients affected by disseminated neuroblastoma, one to twelve years old, were treated with intensive chemotherapy (Vincristine 4 mg/sqm c.i. over 5 days, Melphalan 140 mg/sqm), total body irradiation (TBI) (3.3 Gy for 3 days), and unpurged autologous bone marrow transplantation (ABMT) since October 1984 until November 1987. Thirty-two patients were in complete response (first group) and 7 had residual disease (second group) after an intensive chemotherapeutic induction regimen. Actuarial overall survival at 38 months is 52% and disease free survival at 30 months is 28% for the first group. Actuarial overall survival at 25 months is instead 14% for the second group related treatment toxicity has not been too high (3 deaths). PMID- 2247631 TI - Total body irradiation and high-dose melphalan with bone marrow transplantation at Istituto Nazionale Tumori, Milan, Italy. AB - The technique of total body irradiation (TBI) developed at Istituto Nazionale Tumori, Milan, Italy, is described. This technique consists of i) administration of 12.5 Gy and 14.85 Gy TBI for autologous and allogeneic bone marrow transplantation respectively; ii) in all cases in vivo dosimetry of absorbed TBI dose; and iii) radiation doses to lungs higher than previously described. As of June 1988, seventeen patients with Hodgkin's disease and four with lymphoblastic lymphoma received TBI and 120-180 mg/m2 melphalan. Respiratory function was prospectively evaluated demonstrating moderate and transient reduction of pulmonary function. PMID- 2247632 TI - Clinical results of TBI for bone marrow transplantation at Sevilla. AB - We report on a series on 81 patients affected with acute leukemia undergoing TBI prior to BMT. An analysis of the achieved results is given, emphasizing the limited incidence of interstitial pneumonitis in our patients (3.7%). A suitable patient selection and treatment technique is also needed. PMID- 2247633 TI - Total body irradiation and bone marrow transplantation for immunodeficiency disorders in young children. AB - Congenital immunodeficiency disorders such as severe combined immunodeficiency disease (SCID), Wiskott-Aldrich syndrome, and Chediak-Hegashi syndrome are almost uniformly fatal with most children dying before age one. Allogeneic bone marrow transplant (BMT) is the treatment of choice. Few of these children have matched donors. We use bone marrow processing techniques that allow us to utilize marrow from the parents. Children who lack HLA-identical donors are offered haploidentical, T-cell depleted parental BMTs. Some of these children do not have an immune deficiency severe enough to allow durable engraftment of processed mismatched bone marrow. Successful engraftment may necessitate the use of immunosuppression. Total body irradiation (TBI) is part of our intensive conditioning regimen for children with Wiskott-Aldrich and Chediak-Hegashi syndrome and most children with SCID who have undergone an unsuccessful prior mismatched, T-cell depleted BMT, or who have a high likelihood of donor marrow rejection based on pre-transplant immune function testing. TBI is considered extremely toxic therapy in infancy, with little information available on the acute and chronic effects. The 10 children presented in this report are among the youngest to have received TBI. Five patients were 2 to 6 months of age when they received TBI. The conditioning regimen for all patients was; antithymocyte globulin (25 mg/kg/day, x 3 days), cyclophosphamide (60 mg/kg/day, x 2 days), and TBI. 7.0 Gy TBI was given as a single dose AP-PA at approximately 15 cGy/min. Half value blocks shielded the brain, eyes and lungs. Six of 10 children were alive from 7 to 72 months post transplant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247634 TI - Clinical and physical aspects of total body irradiation for bone marrow transplantation in Nijmegen. AB - Eighty-nine patients were transplanted with allogeneic bone marrow after a standard conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (2 x 4.5 Gy) with average dose rates of 4.1 and 12.3 cGy/min, respectively. The average rectum and lung dose was 9.2 +/- 0.45 and 7.5 +/- 0.78 Gy. In vivo dosimetry was performed in 71 patients irradiated with 18 MV X-rays from left and right lateral. Forty-three patients (48%) died. After increasing the dose rate the incidence of interstitial pneumonitis increased, but the number of relapses decreased. PMID- 2247635 TI - Clinical results and the Essen concept of TBI. AB - Total body irradiation (TBI) prior to bone marrow transplantation (BMT) is applied for treatment of 230 patients in the period 1975-1988. The clinical results of 169 patients treated by four different TBI dosage and treatment techniques are analysed. The risk of leukemic relapse is low after fractionated TBI (9%) as well as after single dose TBI (14%). The lowest frequency of interstitial pneumonitis (21%) occurred when the patient translation technique was used for fractionated homogeneous pa/ap TBI with 10 Gy (8 Gy lung dose) in 4 fractions in 4 days. Prophylaxis of GVHD and the modus of protective environment were two other factors which influence the risk of IP. PMID- 2247636 TI - Interstitial pneumonitis and venocclusive disease of the liver after bone marrow transplantation. AB - One hundred and seventy patients were analysed for interstitial pneumonitis and 151 for venocclusive disease of the liver after bone marrow transplantation. We present our results with emphasis on the role of the parameters of single fraction total body irradiation. PMID- 2247637 TI - Total body irradiation: clinical experience at the Institute Jules Bordet. AB - Our clinical experience with 58 patients receiving TBI as part of their treatment for a malignant hematopoietic disease suggests the following comments: 6 daily fractions of 2 Gy given over 6 days have a similar antitumoral effect as a single dose of 10 Gy, using a low dose rate, but with less toxicity. 7 daily fractions of 2.25 Gy given over 8 days exceed normal lung tolerance. No leukemia recurrence was observed among patients treated with 6 times 2 Gy but the maximal period of observation is only 560 days. On the other hand, a relapse was seen 2 years after 7 times 2.25 Gy. This may suggest the necessity to find a more effective drug regimen or to deliver additional radiation to possible sanctuary sites for chemotherapy. PMID- 2247638 TI - Results of fractionated TBI prior to bone marrow transplantation in standard risk leukaemia at Marseille. AB - One hundred and six patients with standard risk leukaemia were given fractionated TBI prior to allogeneic (72 cases, 27 of whom were T-depleted) or autologous (34 cases) bone marrow transplantation (BMT). Disease free survival at 5 years is 68% for allogeneic non T-depleted BMT and 33% for T-depleted BMT. Deaths are related to relapse, GVHD, infections, pneumonitis, encephalitis, VOD, AIDS, rejection. PMID- 2247639 TI - Total body irradiation before allogeneic and autologous bone marrow transplantation: a ten year Genoa experience. AB - Since 1976 in Genoa, 291 TBI treatments were performed. Before allogeneic BMT, 1000 cGy/1 fx were prescribed in the first 22 patients, and then 990 cGy/3 fx/3 d in AML and CML, and the same or 1200 cGy/6 fx/3 d in ALL. Survival (S) and probability of remaining in remission (PRR) were 54% and 69% at 80 months in 80 AML; in 62 CML 45% and 60% at 60 months; in 69 ALL, 32% and 45% at 82 months. Differences in favour of higher doses and dose rates were observed and are presented. Before autologous BMT, 1000 cGy/1 fx were prescribed to AML and NHL, and 1200 cGy/3 fx/3 d to ALL patients. Disease free survival (DFS) was 71% and 13% at 82 months in 21 AML treated in first R and 9 ALL, respectively; 81% at 32 months in 11 NHL treated in R. PMID- 2247640 TI - Renal insufficiency after total body irradiation for pediatric bone marrow transplantation. AB - Between 1980 and 1987, 59 children with acute lymphoblastic leukemia (ALL) or stage IV neuroblastoma (NB) underwent allogeneic or autologous bone marrow transplantation (BMT). Thirty-nine of these patients were alive and in remission 6 months post BMT and were evaluable for this analysis. Sixteen have developed renal dysfunction. Eight were transplanted for relapsed ALL and received an autologous transplant. Preparation included tenopiside (VM 26), cytosine arabinoside, and cyclophosphamide followed by total body irradiation (TBI). One patient received 850 cGy in a single fraction, while all other patients received fractionated TBI (1200-1400 cGy in 6-8 fractions over 3-4 days). Eight of 11 evaluable patients who received a BMT for NB have developed late renal problems (4-7 months after BMT). The preparation for neuroblastoma patients included VM 26, cis-platinum, melphalan, cyclophosphamide and fractionated TBI (1200-1296 cGy). All 8 neuroblastoma patients had received cis-platinum as induction treatment prior to transplantation. All patients presented with anemia, hematuria and elevations of BUN and creatinine. Renal biopsies were consistent with radiation nephropathy. In conclusion, a high incidence of renal dysfunction has occurred after BMT in children with neuroblastoma and ALL. The clinical and laboratory features are consistent with either radiation nephropathy or hemolytic uremic syndrome. The relatively young age of these patients and conditioning with intensive multi-agent chemotherapy may decrease the tolerance of the kidney to radiation injury. PMID- 2247641 TI - Total body irradiation for bone marrow transplantation in Edinburgh: techniques, dosimetry and results. AB - Total body irradiation, as practiced in Edinburgh as part of the preparation for bone marrow transplantation, is described as regards prescription, techniques, physical data and dosimetry. Clinical results are briefly summarised in terms of disease, status at transplant, survival figures, survival times and causes of death. PMID- 2247642 TI - Technique, dosimetry and results of total body irradiation in preparation to ABMT in Torino. AB - Twenty-five patients with haematologic malignancies received total body irradiation (TBI) as part of their conditioning regimen prior to autologous bone marrow transplantation (ABMT). TBI was delivered with an 18 MeV photon beam through AP-PA ports; the total dose was 13.2 Gy/8 fractions over 4 days; shields were used to limit the total dose to the lung to 8-10 Gy. Five relapses were observed; among 14 patients with ALL or advanced lymphoblastic lymphoma, 10 patients are currently alive and free of disease. Acute and late morbidity of TBI were low. PMID- 2247643 TI - Fractionated total body irradiation for bone marrow transplantation: clinical results on 66 patients. AB - Short term clinical results of bone marrow transplantation on 66 patients conditioned with fractionated total body irradiation (12 Gy in 6 fractions and 3 days) are presented here. An acute toxic effects incident, similar to that obtained previously, a 27.6% interstitial pneumonitis associated with acute severe graft versus host disease in 77% of cases, 19.2% relapses, and 41% total crude survival with an actuarial probability of surviving for more than two years of 46% for ALL, 64% for AML and 28% for CML, are the results obtained since now. PMID- 2247644 TI - Late effects of total body irradiation and cytostatic preparative regimen for bone marrow transplantation in children with hematological malignancies. AB - Twenty-seven children, surviving disease-free for more than 1 year after allogeneic bone marrow transplantation (BMT) for hematological malignancy were evaluated for the long-term effects on endocrine function, sexual development, physical growth, appearance of ocular cataract and psychological sequelae. The growth rate was not decelerated in the prepubertal period in children not affected by chronic graft-versus-host (GVH) disease and without previous cranial irradiation. Development of sexual characteristics was delayed in 4 relevant cases. Thyroid function was not adversely affected, gonadal function was impaired in girls, transplanted after menarche, ocular cataract developed in all cases, irradiated without shielding of the eyes after 4 years. Psychologically, children after BMT had an advantageous social development. PMID- 2247645 TI - Late effects of total body irradiation in correlation with physical parameters. AB - Clear and complete documentation of the physical parameters of total body irradiation (TBI) is one of the essential requirements for the evaluation and improvement of the clinical results of TBI. Concerning the dosimetric aspects of TBI, a number of recommendations have been formulated with emphasis on basic dosimetry, patient dosimetry and dose specification. The dosimeters should be calibrated regularly with reference to the absorbed dose in water. Depth dose measurements should be performed in water equivalent phantoms of specified dimensions. It has been strongly suggested to measure the absorbed dose at the surface of the patient at 8 different regions at the entry and exit of the beam under TBI conditions. The reference dose to the patient should be specified as the total dose to mid abdomen at the height of the umbilicus. As an independent parameter, the lung dose should be specified as the mean dose in the central region of the shielded part of both lungs. Recent, more complete, information on the physical and dosimetric aspects of TBI will be incorporated in the registry of the European Bone Marrow Transplant Group (EBMT). A cooperation has been established between the EBMT and the European Late Effects Project Group (EULEP) to study the development of late effects in man caused by ionising radiation. PMID- 2247646 TI - Bone marrow transplantation: indications and technique. AB - Bone marrow transplantation has emerged during the last two decades from a highly experimental procedure to an accepted therapeutic modality which is carried out at more than 175 institutions worldwide. This paper summarises the indications for this therapy and describes, in short, the techniques of the different consecutive steps involved in bone marrow transplantation. PMID- 2247647 TI - Immunohematological aspects of total body irradiation and bone marrow transplantation for the treatment of leukemia. AB - Total body irradiation combined with high dose cyclophosphamide followed by allogeneic bone marrow transplantation has proved to be a highly effective treatment for acute leukemia. However, a most troublesome complication was GVHD which occurred in a high proportion of patients. In spite of the application of immunosuppressive drugs after the transplantation, GVHD caused 25% mortality in these patients. Depletion of T lymphocytes from the donor bone marrow prior to grafting has proved to be highly effective in preventing GVHD. Experiments with monkeys and dogs demonstrated that engraftment of T cell depleted marrow requires an increase of the TBI dose for conditioning. Most clinical transplant teams that did not adjust their conditioning regimen reported a high incidence of graft rejections following the use of T cell depleted marrow, as well as an increased relapse rate. Transplant teams that increased their conditioning dose of TBI report an excellent take of T cell depleted marrow. On the basis of the relation between leukemia cell kill and probability of relapse, taking into account the radiosensitivity of leukemia cells, it can be calculated that the graft-versus leukemia effect experienced with unmodified bone marrow grafts equals 1 log leukemic cell kill. This extra anti-leukemic effect is provided by the larger TBI dose employed to achieve full engraftment of T cell depleted marrow. However, increasing the immunosuppression by conditioning with anti-lymphocyte sera or TLI is not expected to prevent an increased relapse rate, since these conditioning modalities do not provide the necessary extra killing of leukemic cells. PMID- 2247648 TI - Prediction of effects of therapeutic total body irradiation in man. AB - Total body irradiation (TBI) is an important but toxic element in the preparation of patients for bone marrow transplantation. TBI can be delivered in many different ways and analysed for many different endpoints. The published clinical and large animal experiences are reviewed to economise the search for more optimal irradiation schedules. Currently, the immunosuppressive effects and potentially lethal side effects of TBI appear to be the dominant determinants in the therapeutic ratio of TBI. Radiation survival curve parameters are estimated for bone marrow, intestines, lung and immune system in an effort to predict fractionation effects of TBI. Predictions are in reasonable agreement with retrospective clinical observations in patients and animals. High dose rate TBI, fractionated in doses greater than 2 Gy and given over 4 days or less are recommended. Further optimization attempts depend on patient's diagnosis, available bone marrow donor, lymphocyte depletion of bone marrow and prior sensitisation of recipient. Deliberate TBI dose inhomogeneities might improve the therapeutic ratio of TBI, but remain to be explored in greater detail. The proposed model for predicting TBI effects can be adapted and remain useful for future use, when more quantitative information on additional important transplant variables becomes available. PMID- 2247649 TI - Dose rate and fractionation of total body irradiation in dogs: short and long term effects. AB - Variations of regimens of total body irradiation (TBI) were investigated in the dog as a preclinical model for bone marrow transplantation. Inactivation of hemopoietic precursor cells (CFU-GM) was studied following irradiation of marrow in vitro, following TBI at sublethal doses in vivo and following autologous transplantation of marrow obtained after sublethal TBI. Inactivation and recovery of CFU-GM as well as restoration of hemopoiesis following autologous transplantation was independent of the dose rate, but nadirs of blood counts were lower following sublethal TBI with the higher dose rate. Acute non-hemopoietic toxicity of TBI depended on the dose, the dose rate and the total treatment time and not on the fractionation regimen. At a total dose of 25 Gy acute mortality was prevented by prophylactic administration of oral, non-absorbable antibiotics. Late mortality was due to degenerative and autoimmune-like disorders with or without infections and to malignant tumors. Evaluation of long-term survival is still preliminary, since surviving dogs of two groups (10 Gy as single dose, 25 Gy as hyperfractionated TBI) have not yet reached the median survival time of their group. So far, long-term survival depended on the total dose (p = 0.05) and, possibly, the fractionation regimen (p = 0.12). The latency period until development of malignant tumors was influenced by the total doses given in the same treatment time (p = 0.05) and by the total treatment time for equal doses (p = 0.04). It was concluded that TBI at a low dose rate may give the best therapeutic ratio of inactivation of hemopoietic precursor cells to acute toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247650 TI - Clinical basis for TBI fractionation. AB - Most available clinical data strongly suggest a sparing effect of TBI fractionation for the lungs, liver, lens, the growth cartilage and, perhaps the prepubertal ovary; the usual fractionated TBI regimens, delivering from 12 to 15 Gy, appear to be constantly less toxic than the "standard" 10 Gy single dose TBI scheme. However, there is also some clinical suggestion, essentially coming from the T-depleted graft experience, that the largely used 12 Gy fractionated scheme (6 X 2 Gy) might be less effective than the standard 10 Gy single dose TBI for leukemia cell killing and for eradication of the recipient bone marrow. Additional clinical data, ideally coming from well designed randomised trial or from careful large-scale retrospective evaluations, should help to optimize the TBI delivery. PMID- 2247651 TI - Total body irradiation for bone marrow transplantation: the Memorial Sloan Kettering Cancer Center experience. AB - In May 1979, Memorial Sloan-Kettering embarked on a programme of hyperfractionated TBI (HFTBI), 1320 cGy in 11 fractions over 4 days with partial lung shielding (1 HVL), followed by cyclophosphamide (60 mg/kg/d x 2d) for cytoreduction prior to allogeneic bone marrow transplantation (BMT). Anterior and posterior chest wall electron "boosts" were given to the areas blocked (600 cGy in 2 fractions) on the last two days of treatment. Since then, we have treated over 600 patients with HFTBI, the majority for allogeneic BMT. Several modifications have occurred over the years. We have added a "boost" electron dose of 400 cGy to the testes in all male leukemic patients; this reduced testicular relapses from a rate of 14% (4/28) to 0%. In an attempt to increase engraftment of T-depleted BMTs, we added one additional fraction; since our present dose/fraction was also increased to 125 cGy, we now deliver a total dose of 1500 cGy in 12 fractions over 4 days for allogeneic transplants. Tolerance to HFTBI has been excellent relative to the single dose (SD) regimen utilised prior to May, 1979. The incidence of fatal interstitial pneumonitis (IP) decreased from 50% in the SD regimen to 18% after the introduction of HFTBI. In children, the incidence of IP was only 4% with HFTBI. With the introduction of T-depleted marrows, fatal IP in adults has decreased also, e.g. to less than 10% in CML patients. With conventional BMT after HFTBI, relapse at 5 years has been exceedingly low (e.g. in children, 13% for ALL, 2nd remission and 0% for AML, 1st remission) and engraftment has been 100%. With matched T-depleted BMT, rejections have occurred in 15% overall; the incidence of graft failure has not been reduced by the higher dose of HFTBI. Relapses in this setting are equivalent to relapses with conventional BMT for AML, but appear to be increased for ALL. Radiobiological findings related to HFTBI will also be discussed. PMID- 2247652 TI - Late effects in children receiving total body irradiation for bone marrow transplantation. AB - Bone marrow transplantation is a life-saving procedure for an increasing number of children and young adults. As greater number of patients continue to receive this procedure and are cured of their underlying hematologic disorder, greater attention must be given to the delayed effects, especially those which do not appear until years after the transplant procedure. Children who are cured of their underlying disease continue to visit the hematologist/oncologist, but with decreasing frequency as time increases following the curative therapy, and at the same time increase the relative frequency of visits to their pediatrician. Thus, it is imperative that the primary care pediatrician be aware of the details of the patient's previous medical history, especially of chemotherapy and irradiation therapy which may have been given, in order to anticipate the delayed effects. Early diagnosis of thyroid and GH deficiencies with institution of appropriate hormone therapy may prevent subsequent development of thyroid malignancy and may improve the child's growth and development. Recognition of cataracts and dry eye syndrome is necessary to prevent visual difficulties. Careful oral examination and attention to the child's general neurological presentation and inquiry regarding school performance is important in recognising dental difficulties, learning difficulties and early recognition of development of tumors of the head and neck. Attention to details, early recognition of problems and early therapy of the problems is needed to improve the quality of life for these unique patients. PMID- 2247653 TI - Radiosensitivity in Fanconi anemia: application to the conditioning for bone marrow transplantation. AB - Fanconi anemia is characterised by pancytopenia, malformations and chromosomal breaks probably related to a congenital defect of DNA repair mechanisms. The evolution is always fatal unless, the patient receives a bone marrow transplant from an HLA identical sibling. According to preliminary work on sensitivity of FA cells to alkylating agents and to in vivo radiosensitivity tests, we used a modified conditioning regimen with cyclophosphamide 20 mg/kg and 5 Grays thoraco abdominal irradiation. Nineteen patients are reported. The actuarial survival is 74% with a median follow-up time of 4 years (range 6 months to 6 years). GVH was the main complication (58%). It was responsible directly or indirectly for 4 deaths. These results show that BMT in FA is successful in the large majority of cases. The decrease of the dose cyclophosphamide allowed a good engraftment without major toxicity. Studies are in progress for using this type of protocol in situations without a HLA matched sibling donor. PMID- 2247654 TI - Major complications of the central nervous system after bone marrow transplantation in children with acute lymphoblastic leukemia. AB - After the first ten bone marrow transplantations for acute lymphoblastic leukemia in children, we evaluated the cerebral outcome as severe cerebral complications had occurred in these patients. From these data we deduced a score of risk factors (SRF) encompassing the facts known to cause cerebral damage in leukemia treatment. In the following 13 patients, we lowered, in the individual patient, the SRF. The number of patients with cerebral damage was lower and no cerebral death occurred. PMID- 2247655 TI - TBI technique and clinical results of leukemia patients at the University of Tubingen. AB - Since 1976, more than 180 patients suffering from leukemia or aplastic anemia have been treated with BMT and TBI. The improvement of TBI-technique starting from single fraction irradiation without any shielding to different types of fractionation schemes with lung, head and neck shielding and an electron boost to the thoracal wall is shown. A more detailed description of the actual TBI technique is given; this has been applied to 64 patients to-date. Some clinical results are summarised into four subgroups. Life table analyses are shown for single fraction irradiation as well as for fractionated irradiation separated for high and for low risk patient groups. PMID- 2247656 TI - [The 11th Quality Control Survey for Radioisotopes in vitro Tests in Japan, 1989. Subcommittee for Radioisotopes in vitro Test, Medical and Pharmaceutical Committee, Japan Radioisotope Association]. PMID- 2247657 TI - [Perfusion study of the pulmonary hilar region by SPECT--normal cases]. AB - Alveoli in the hilar region comprise the peripheral area containing daughter branches from subsegmental or one more divisional peripheral bronchi. Pulmonary perfusion in hilar region was examined by SPECT (single photon emission CT) in ten normal volunteers. ROI (region of interest) in the axial images were set in the hilar region, the upper, middle and lower lung fields with 10.8 mm thickness. Counts/one pixel (C/P) were calculated in these ROI. There was a tendency of C/P increase from upper to lower lung field. And there were no significant differences in C/P increase between hilar region and other axial fields. In the chronic obstructive pulmonary diseases, however, ventilation studies in the previous reports using Xe dynamic CT or PET (positron emission tomography) showed differences between outer region and hilar region. This method will be expected to evaluate the pulmonary perfusion not only in the whole lung but in different lung areas, including the hilar region in the chronic obstructive pulmonary diseases. PMID- 2247658 TI - [Relationship between the total IgE levels and specific IgE antibodies]. AB - In this study, nine allergens were selected; i.e. 1289 cases of d1, 1277 cases of e1, 1547 cases of f1, 1063 cases of t17 and others, for investigating the relationship between the total IgE level and RAST score. The results showed that the total IgE level was high in high d1 score, and 29 cases of low IgE level were observed in high f1 score groups. On the other hand, the comparison of the CAP system and the total IgE level showed. The result shows that one case of low total IgE value was found in highest d1 score group. PMID- 2247659 TI - [A comparison of the several methods for determination of specific IgE antibodies]. AB - The accuracy of measurement using kits in the clinical laboratories is important for the patient diagnosis and treatment. In the present paper, the AL-18, AlaSTAT, CAP, FAST and RAST methods were investigated and were compared among kits the results obtained with serum sample, for determination of specific IgE antibodies. Significant differences among kits were observed from the results of those methods. One of the reasons, why the data discrepancy exists, is that each kit uses a different reference and a different inclusion method of allergen. For the evaluation of data discrepancy among those kits, it might be important that the clinical history of symptoms and in vivo tests against the different allergens compared with results of in vivo tests. PMID- 2247661 TI - [Transmission of 1 cm dose equivalent]. PMID- 2247660 TI - Interlaboratory comparison of low-level organic tritium measurement in environmental samples. PMID- 2247662 TI - [Measurement of radiation energy and its application. V. Measurement of gamma-ray energy and its application (3) Application of gamma-ray energy measurements]. PMID- 2247663 TI - Adverse reactions to inhaled drugs. PMID- 2247664 TI - Local anaesthesia for fibreoptic bronchoscopy--where are we now? PMID- 2247665 TI - Respiratory muscle weakness. PMID- 2247666 TI - Combined cryptogenic fibrosing alveolitis and emphysema: the value of high resolution computed tomography in assessment. AB - Simple tests of lung function may be misleading in the assessment of patients with interstitial lung disease. Eight patients are described with cryptogenic fibrosing alveolitis (histologically proven in four) with severe breathlessness and low gas transfer (median DLCO 32.4%, range 9.2 to 35.3%, % predicted) in whom lung volumes were preserved [median VC 98.7, range 67.5-131.1%; median TLC 92.5, range 88.1 to 121.2, (% predicted)], and in whom there was no evidence of airflow obstruction [median FEV1/FVC 84.6, range 68-116 (% predicted)]. All were current or ex-heavy smokers. Thoracic high resolution computed tomography revealed upper zone emphysema, the extent of which was not appreciated using conventional chest radiography. The atypical physiological and radiological features can be explained by coincidental cryptogenic fibrosing alveolitis and emphysema and high resolution computed tomography was valuable in the assessment of these patients. PMID- 2247667 TI - Reproducibility of methacholine induced bronchoconstriction in healthy subjects: the use of area under the expiratory flow-volume curve to express results. AB - The usefulness of the pulmonary function variable, area under the expiratory flow volume curve (AEFV), in methacholine provocation (MP) studies in normal subjects was evaluated. The baseline coefficients of variation (CV), maximal fall from post-saline values (MAX) and dose-response slope [DRS = maximal percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumol)] were calculated for AEFV, and were compared to those of forced expiratory volume in one second (FEV1), maximum expiratory flow at 50% (MEF50%) and at 25% (MEF25%). Also the repeatability after 2 and 8 weeks was assessed. The rank order of CVs was FEV1 less than AEFV less than MEF50% approximately MEF25% all differences, except MEF50% vs. MEF25%, being significant (P less than 0.05). The order of sensitivities (estimated with MAX and DRS) was FEV1 less than AEFV less than MEF50% less than MEF25%. Again, all differences were significant (AEFV vs. MEF50% P less than 0.01, others P less than 0.001). After two weeks the correlation coefficients for MAX- and DRS-values of AEFV were 0.84 and 0.94 (P less than 0.001), respectively. After an eight week period the correlations were still high, 0.86 and 0.92 (P less than 0.001), respectively, but the actual MAX- and DRS-values tended to be smaller than eight weeks before. The repeatability of MAX of AEFV was not quite as high as that of FEV1. On the other hand, the correlations of DRS-value derived from AEFV were markedly better than those derived from FEV1. In conclusion, MP in normal subjects is well repeatable at least within two weeks, but after an eight week period disturbing factors may intervene reducing repeatability. AEFV can be considered at least as good a pulmonary function variable as FEV1 in demonstrating bronchoconstriction during MPs in normal subjects, and it might even be a better variable to obtain DRS values than other variables tested. PMID- 2247668 TI - Changes in tonsillar bacteriology of recurrent acute tonsillitis: 1980 vs. 1989. AB - Recurrent acute tonsillitis is a common problem. Despite this, there still remain many controversies regarding aetiology and correct management. The tonsillar microflora of 33 children with recurrent acute tonsillitis studied in 1980 and 58 patients studied in 1989 is presented. A comparison of the microbiology in the two periods studied a decade apart suggests that the pathogenic profile is changing. Haemophilus influenzae increased from 39 to 62% in the deep tonsillar tissue in the decade. There was a concomitant increase in incidence of Staphylococcus aureus from 6 to 40% of cases. In the same interval, mixed microflora increased from 18 to 52%. Anaerobic organisms were isolated in insignificant numbers. Unique to this study, 44% of H. influenzae isolates in 1989 were beta lactamase producers, increasing from only 2% in 1980. All of the S. aureus were beta lactamase producers. In the majority, the throat swabs grew only organisms commensal to the upper respiratory tract however, the deep tonsillar tissue excised at tonsillectomy carried significant growths of pathogenic organisms confirming the inadequacy of the superficial tonsillar swab as an indicator of treatment. PMID- 2247669 TI - Pulmonary non-Hodgkin's lymphoma mimicking infection. AB - Progressive pulmonary shadows prompted investigations which provided the diagnosis of pulmonary non-Hodgkin's lymphoma in three patients (two with the acquired immunodeficiency syndrome). Rapid progression of radiographic abnormalities seen in these three patients is unusual for pulmonary non-Hodgkin's lymphoma and mimics disease evolution commonly associated with pulmonary infections. PMID- 2247671 TI - Cavitary lung disease caused by Mycobacterium avium-intracellulare in AIDS patients. PMID- 2247670 TI - Local anaesthesia for fibreoptic bronchoscopy: comparison between intratracheal cocaine and lignocaine. AB - In a double-blind study of 60 patients undergoing fibreoptic bronchoscopy we have compared the local anaesthetic effects of intratracheal injections of cocaine (4 ml, 2.5%) and lignocaine (4 ml, 4%). The two local anaesthetics were equally effective in terms of cough suppression, requirement for extra local anaesthetic, patient discomfort and operator acceptability. PMID- 2247672 TI - Pleurisy and hepatic cysts. PMID- 2247673 TI - Dressler's syndrome after meningococcal myopericarditis. PMID- 2247674 TI - Simple exercise testing. PMID- 2247675 TI - Lung inflammation and injury: models and mechanisms. Abstracts of the 9th summer meeting of The British Association for Lung Research. Edinburgh, 3-4 September, 1990. PMID- 2247676 TI - [The reform of medical education]. PMID- 2247677 TI - [Treatment of anemia with recombinant human erythropoietin and the bone marrow response in uremic patients undergoing periodic hemodialysis]. AB - Treatment of anemia with human recombinant erythropoietin (EPO-R) and its effect on bone marrow was studied in 10 anemic patients on periodic hemodialysis (HD). Blood transfusion was not required once treatment started. Hemoglobin (Hb) levels normalized at six months in all patients (7.2 +/- 0.2 vs 12.4 +/- 3 g/dl, p less than 0.01). Serum ferritin levels decreased progressively as Hb increased (r = 0.5609), and six patients needed iron supplement since the third month. Bone marrow iron deposits decreased significantly (p less than 0.001), together with an increase of cellularity and improvement of erythrodysplasia. EPO-R was associated with worsening hypertension in previously hypertensive patients, although it could be controlled with more aggressive treatment. Thrombotic events either systemic or at the vascular access, were not observed. EPO-R corrects the anemia in uremic patients undergoing HD. Iron stores and blood pressure in hypertensive patients on treatment with EPO-R must be monitored regularly. PMID- 2247678 TI - [Hospital infections at the medical Infection Surveillance Unit from 1984 to 1988]. AB - The aim of the present work was to study hospital infection tendencies and to analyze the variations that have occurred in the accumulated incidence, the localization and the responsible microorganisms in a medical ICU of the Hospital Ramon y Cajal, Madrid during a 5 years period. Nosocomial infections appear with a statistically significant decreasing tendency: the simple regression curve, estimated from the monthly accumulated incidence, presents a slope = -0.16 (p less than 0.05); the adjustment made with the annual accumulated incidence values shows a slope = -2.15 (p less than 0.001). The most frequent localization of hospital infections were: lower respiratory tract, urine, and blood. These infections show in general a decreasing tendency existing a statistical difference in respiratory = -1.5 (p less than 0.001) and urinary = -1.48 (p less than 0.001) infections. The microorganisms most frequently isolated in these patients were P. aeruginosa, S. marcescens and E. coli. PMID- 2247679 TI - [Effect of castration on bone mineral metabolism in rats]. AB - We have tried to experimentally determine what effect castration is going to have on rats bone and on the main mineral bone regulatory hormones. Twenty ovariectomized female rats and their age and weight matched controls were used. Parathormone, calcitonin, osteocalcin and serum calcium levels were determined as well as mineral bone content and head of femur density. Castration produces, in rat, a marked decrease in circulating calcitonin, parathormone (PTH) and bone density, with no changes in mineral bone concentration. Finally, castration produces a slight increase in osteocalcin serum levels although without a statistical value. PMID- 2247680 TI - [Cavitated pneumonia and toxic shock syndrome: presentation of a case]. AB - Toxic shock syndrome (TSS) is a potentially fatal acute disease preferentially affecting menstruating women and is related to the use of vaginal tampons seems to be due to an specific exotoxin produced by some Staphylococcus aureus strains. We present here the case of a male patients suffering cavitated pneumonia who developed a systemic clinical picture comparable to TSS. This unusual form of presentation is discussed as well as the diagnostic criteria which define this entity. PMID- 2247682 TI - [A comparative study of 2 proposed reforms--1934 and 1989--in the teaching systems of medical schools in Spain]. PMID- 2247681 TI - [Knowledge and attitudes of ambulatory patients regarding various aspects of pharmacologic treatment]. AB - Recognizing the patients believes and attitudes towards their disease and treatment as well as facilitating basic information are essential for a satisfactory compliance. In this respect, and in order to know the state of things, personal interviews were carried out following a pre-established protocol and evaluating the degree of acceptance of information oriented to the outpatient. Two hundred and seven questionnaires were collected. Populations mean age was 50 years, 60% were women and there was a high percentage of illiterate patients or with only primary school level (69.8%), with a medium-low social status (98%). In general, they were aware of the indication of treatment (80%) although 56% of patients did not know the consequences of a poor control of their disease. Seventy eight percent wished to receive more information and 147 (96%) patients preferred the physician as the provider of it. The opinion regarding the information leaflets oriented towards the outpatient was unanimously favorable being the most interesting aspects those regarding the instructions on the use of drugs and adverse effects. The educational level was the factor influencing most significantly the patient's attitude. We conclude saying that in order to carry out a pharmacological treatment educational program it is necessary to evaluate the knowledge, needs and attitudes of the population towards whom it is directed. PMID- 2247683 TI - [A 58-year-old patient with hemodynamic compromise coming from the Mostoles General Hospital for treatment]. PMID- 2247684 TI - [Crohn disease metastatic to the skin]. PMID- 2247685 TI - [Bacterial resistance in non-hospital urinary tract infections]. PMID- 2247686 TI - [Paratesticular myxoid liposarcoma in a child]. PMID- 2247687 TI - [Subacute de Quervain thyroiditis associated with typhoid fever. Description of a case]. PMID- 2247688 TI - [Which is the standard tuberculin test?]. PMID- 2247689 TI - [Ulcerative colitis and fungemia caused by Candida parapsilosis]. PMID- 2247690 TI - [Diabetes mellitus in the elderly: we should suspect a neoplasm of the pancreas]. PMID- 2247691 TI - [Lymphomatoid granulomatosis: presentation of a case with multiple organ involvement and T-cell proliferation]. PMID- 2247692 TI - [Hospitals and immigration: analysis of a case series]. AB - The "immigrants problem", with the inevitable social aspects which this new phenomenon involves, has grown lately into a matter of primary interest to the public opinion of our country. The hospital too, in its capacity as leader among the sociosanitary institutions, has witnessed a change to some extent of the demand for services resulting from this reality. The Authors intend therefore to re-define here the whole body of a large metropolitan hospital patients, referring to an extensive statistical information and analyzing with special attention the statistics about foreign citizens. To this purpose they have considered all the cases of hospitalization occurred during a five-year period, from 1985 to 1989. The gathered data have been elaborated and analyzed from a more strictly demographic standpoint and (in particular) from the epidemiological point of view, comparing the data resulting among the immigrants with those regarding the whole body of hospitalized people during the same period. The data so obtained show, in spite of some significant differences due almost certainly to social differences, a superimposition on the italian reality, reproducing on a smaller scale its distinctive features. Even if this research is restricted to a specific situation, the results obtained can be considered a basis to make further similar studies within other hospital structures, in order to point out the different and variable demands for hospital services originating from this new social reality. PMID- 2247693 TI - Breast involvement in malignant blood diseases. A report of four cases and review of the literature. AB - The breast involvement in malignant blood diseases is a very rare manifestation. Four cases observed by the Author in the last 12 years, consisting of one male with Multiple Myeloma (MM) stage III A, and three females with Non-Hodgkin lymphoma (NHL), in IA-E, IIIA-E and IV A stage respectively are described. The presence of breast plasmacytoma, lymphoblastic or lympho-plasmocytic type lymphoma observed in 3 of 4 cases has been rarely reported. PMID- 2247694 TI - [Still's disease in adults: diagnostic problems]. AB - Still's disease is a seronegative arthritis of children which, in a limited number of cases, can affect adults. The diagnosis of adult-onset Still's disease is characterized by high fever, arthritis and negative serologic tests for rheumatoid factor and antinuclear antibodies and by at least two minor symptoms (leukocytosis, evanescent rash, serositis, hepato- or splenomegaly, and lympho adenopathy). Since many diseases present analogous manifestations and the adult onset Still's disease is generally diagnosed by exclusion, we report two patients, aged 26 and 39, with Still's disease, the former with a classic clinical feature, the latter with a clinical feature characterized by severe hepatic abnormalities. The determination of histocompatibility antigens can be useful because some of them (HLA-DR4 in case 1 and HLA-DRw6 in case 2) are frequently associated with the adult-onset Still's disease. The role of anti inflammatory therapy (acetylsalicylic acid, indomethacin, steroids) must be emphasized, whose efficacy can constitute the pathognomonic element on which the diagnosis of adult-onset Still's disease can be based in a proper clinical pattern. PMID- 2247695 TI - [Neoplasms with unknown primary location]. AB - Neoplasms with unknown primary location (U.P.L.N.) represent an important chapter of oncological pathology which has not yet been completely defined regarding diagnostics, therapy and prognosis. U.P.L.N. recur in clinical practice in 0.5% 10% of cases and show equal sharing in both sexes: still mortality is high. This is in agreement with the biological behavior of U.P.L.N. which is that of a neoplastic illness, systemic from the onset and therefore immediately aggressive. Treatments commonly used only slightly alter the course of the disease. If the general state of the patients allows it, treatment must include every available therapeutical remedy (CHR, RDT, CHM) conveniently evaluated in every single case and preferably under the guidance of the apparent histotype and of the onset seat. The histotype of an U.P.L.N. sensibly affects the prognosis of the patient: there is an improvement in well differentiated and lodged forms and conversely, there is a sharp impairment with fast evolution in the less differentiated and variably metastasized forms. In our case-report, the U.P.L.N. rate has been 5.37% on 1786 cancer diagnoses from February 1980 until January 1988. In 65% of these cases, the histotype sustaining the pathology was represented by adenocarcinoma, in 21% by epidermoid carcinoma and in the remaining 14% by undifferentiated carcinoma. The clinical onset most frequently observed has involved the lymph nodes, followed by involvement of the serosa, bones, lungs and liver. Complex therapeutic treatments have not provided clear results, but the use of anthracyclines and cyclophosphamide seems promising. Finally, we suggest the use of immunomodulators (such as interferons, thymus hormone, lymphokines) in association with the classic chemotherapeutics. PMID- 2247696 TI - [Amebic liver abscess: 2 imported cases]. AB - Two imported cases of amebic liver abscess are discussed with regard to laboratory, diagnostic and therapeutic peculiarities. The diagnostic role of ultrasonography and especially of specific serology is stressed, whereas in therapeutic terms, the efficacy of medical approach alone is emphasized even when complications until yesterday surgically treated occur. PMID- 2247697 TI - Peptic ulcer in migrants. Seven case-reports from Italy. AB - Migrant workers in Central Europe are reported to suffer from an increased prevalence of both duodenal and gastric ulcer as compared to native population. No information is available, however, as far as Italy is concerned. The Authors have thought of interest to report on 7 cases of peptic ulcer disease occurring in migrant workers in Italy. Patients were young adult males from African or Mediterranean developing Countries. In 5 cases the symptoms of their peptic ulcers began after their arrival in Italy. The etiopathogenesis of peptic ulcer was likely to include an interaction among emotional stress, low income, shift and manual work, cigarette smoking and nonsteroidal antiinflammatory drugs self administration. This last factor has not been reported in literature. The hypothesis that migrant workers in Italy are a peptic ulcer-prone population needs further confirmation for its clinical and social implications. PMID- 2247698 TI - [Use of immunoglobulins in AIDS]. AB - Fourteen AIDS patients with constitutional symptoms without a known etiology were treated with intravenous immunoglobulins (IVIG). The dosage regimen was 300 mg/kg per day three times weekly for two weeks followed by 300 mg/kg per day once weekly for ten weeks. All patients improved clinically after treatment with IVIG. The reason for the clinical improvement in our cases is as yet unclear, but it is possible that immunoglobulins have had a therapeutic effect on the underlying immunologic disturbance. PMID- 2247699 TI - For a systemic study of arterial pressure. PMID- 2247700 TI - Angioedema. A review on the acquired, allergic or non-allergic, and the hereditary forms. AB - This review intends to review the various clinical and biochemical backgrounds of angioedema: i.e. angioedema in association with allergic or pseudoallergic reactions and the cells involved as well as angioedema on the basis of functional deficiencies of regulatory proteins such as C1-esterase-inhibitor, plasma carboxypeptidase B, and the angiotensin-converting enzyme. Angioedema in suggested association with sexual hormone balance shifts is another topic discussed. The manuscript further summarizes some possible therapies and laboratory practices for diagnostic purposes of the various forms of angioedema. PMID- 2247701 TI - [Diet and autoimmunity]. AB - New data emphasize the importance of nutritional factors in autoimmune diseases. Dietary alterations can be linked to autoimmune disorders as a specific pathogenetic mechanism and also for the malnutrition conditions frequently documented in these patients. The precise function of different nutrients is not completely known as they can be primary pathogenetic agents or causes of acute reacerbations or, finally, simply accompanying phenomena. It is also difficult to modify the intake of a single dietary component and to clarify its metabolic importance for the complexity of metabolic events in the human body and for the possible appearance of cascade-mechanisms. In lipid metabolism the multiple interactions between fatty acids, prostaglandins and leukotrienes are linked to alterations in inflammatory parameters. The exact role of modifications of proteins or of a single amino acid on immune function, also for the possible interference in protein restricted diet of the caloric component, is still unknown. Trace elements and vitamins are certainly important for the control of inflammation and of susceptibility in infections, albeit their role is not clear. More studies are necessary to clarify the link between dietary component and autoimmune diseases. However, study in experimental models and in human Systemic Lupus Erythematosus and Rheumatoid Arthritis demonstrated that a good nutritional homeostasis can contribute to decrease the severity of these disorders and to modify the clinical course with a physiological treatment that is free of side effects. PMID- 2247703 TI - [Cultural and scientific realities of internal medicine studies]. PMID- 2247702 TI - [Oculogenital infections caused by Chlamydia trachomatis]. AB - C. trachomatis, the causative agent of hyperendemic trachoma and lymphogranuloma venereum, is also responsible of sexually transmitted infections. It is now recognized that genital chlamydial infections are the major cause of sexually transmitted diseases in Western industrialized countries, surpassing the importance of gonococcal infections. C. trachomatis, obligate intracellular parasite, enters the epithelial cells of genital mucosae and can reach, luminally, other organs of both female and male genital tract originating different clinical pictures. Vertical transmission of the microorganism from the infected mother to the newborn is of great importance. The infection takes place during delivery and can lead to disease in the newborn such as inclusion conjunctivitis and interstitial pneumonia. The present review deals mainly with clinical features and the most frequent complications of chlamydial infections. The identification of subjects at risk and the improvement of diagnostic techniques is of utmost importance since a prompt antibiotic treatment can eradicate the microorganism at least in uncomplicated infections, preventing the sequelae of the disease. PMID- 2247704 TI - [Internal medicine, specialism, hospitals]. PMID- 2247705 TI - Blastomycosis: fungal infections of the lung update: 1989. AB - Three additions to the understanding of blastomycosis have been noted over the past several years. First, Blastomyces dermatitidis has now been grown from soil in association with epidemics of infection, indicating that microfoci of the organism exist in nature. Second, immune markers of previous infections have been used to help confirm that subclinical or asymptomatic cases occur in endemic areas. This is well recognized for other fungal infections, like histoplasmosis, and is increasingly recognized for blastomycosis. Third, alternatives to amphotericin B have been discovered effectively to treat clinical blastomycosis. Ketoconazole and itraconazole, which are orally absorbed imidazole antifungal agents, have been shown to be impressive antibiotics for blastomycosis that is less than life-threatening. Amphotericin B remains the agent of choice to treat patients with central nervous system or overwhelming blastomycosis. PMID- 2247706 TI - Invasive pulmonary aspergillosis in patients with neoplastic diseases. AB - Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in granulocytopenic patients. The purpose of this article is to review the current understanding of the microbiology, hospital epidemiology, clinical manifestations, diagnosis, prevention, and treatment of invasive pulmonary aspergillosis. Aspergillus conidia (spores) are inhaled from environmental sources into the paranasal sinuses and lower respiratory tract. Persistent fever, pulmonary infiltrates, and pleuritic pain in granulocytopenic patients receiving antibacterial antibiotics is a common manifestation of invasive pulmonary aspergillosis. Computerized tomographic scans of the chest often reveal characteristic peripheral nodules that also may progress to characteristic cavitary lesions. Hemoptysis may develop due either to hemorrhagic infarction during granulocytopenia or to the rupture of mycotic aneurysms during recovery from granulocytopenia. Aspergillus organisms may extend locally from the lung to involve other thoracic structures, including the heart and chest wall, and may disseminate to extrapulmonary sites, such as the brain, where focal neurological deficits ensue. Early diagnosis of invasive pulmonary aspergillosis may be difficult. Isolation of Aspergillus organisms from respiratory secretions of a persistently febrile granulocytopenic patient is usually indicative of invasive pulmonary aspergillosis and should not be dismissed as a contaminant or saprophyte. Amphotericin B is the treatment of choice; however, high dosages (1.0 to 1.5 mg/kg/day) are often necessary. Aspergillosis may develop in granulocytopenic patients who are already receiving empirical amphotericin B in lower doses (0.5 to 0.6 mg/kg/day). It is hoped that further investigation directed toward an understanding of pathogenesis, improving diagnostic methodology, and developing new therapeutic and preventive strategies will improve the outcome of this life-threatening infection. PMID- 2247707 TI - Candidemia and systemic candidiasis. AB - The growing problem of candidemia and systemic candidiasis reflects the enormous increase in the pool of patients at risk as well as the increased opportunity that exists for Candida sp to invade tissues normally resistant to invasion. Candida sp, as truly opportunistic pathogens, exploit recent technological advances to gain access to the circulation and deep tissues. The increased prevalence of local and systemic disease caused by Candida organisms has resulted in new clinical syndromes, the expression of which depends upon the immune status of the host. These new syndromes include the focal hepatosplenic candidiasis, Candida peritonitis and systemic candidiasis. Management of serious and life threatening invasive candidiasis remains severely hampered by the lack of reliable diagnostic methods that would allow early detection of both fungemia and tissue invasion by Candida organisms. Amphotericin B remains the cornerstone of effective antifungal therapy in systemic candidiasis. Over the last decade, new principles have emerged, including shorter and lower dosage regimens for catheter related candidemia. The newer oral azoles may play a useful role in the management of invasive candidiasis. PMID- 2247708 TI - Cryptococcal meningitis in the acquired immunodeficiency syndrome. AB - Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival. PMID- 2247709 TI - Progressive disseminated histoplasmosis in the acquired immunodeficiency syndrome: a model for disseminated disease. AB - Progressive disseminated histoplasmosis (PDH) is a relatively common infectious illness in human immunodeficiency virus (HIV)-infected patients. In Houston, Texas, (which is moderately endemic for histoplasmosis) the frequency of PDH is 5% among patients with acquired immunodeficiency syndrome (AIDS), almost as high as that of those with cryptoccal disease. In highly endemic areas, the frequency of PDH in AIDS is even greater, up to 75% in some areas. It is likely that as the HIV epidemic continues to penetrate to more remote, highly endemic areas, more and more cases of PDH will occur. It is also clear that PDH may develop in HIV infected patients who presently live in nonendemic areas, but who previously resided in endemic areas. It is important that all physicians who care for HIV infected patients become thoroughly familiar with the clinical manifestation of this illness. Timely diagnosis depends on a high degree of diagnostic suspicion since the illness seldom presents with primary respiratory symptoms. It is prudent to consider PDH in the differential diagnosis of any systemic, wasting, febrile illness in HIV-infected individuals, especially if currently or in the past they have resided in areas endemic for the fungus. Similarly, whenever PDH is diagnosed in any patient who is in a high-risk group for HIV infection, prompt testing for HIV should be performed. PMID- 2247710 TI - Coccidioides immitis in patients with human immunodeficiency virus infections. AB - Coccidioidomycosis in human-immunodeficiency virus-infected patients poses frequent and significant problems. Most cases are presently concentrated in regions highly endemic for the fungus. Infection most frequently involves the lungs, and diffuse reticulonodular infiltrates are typical. Disease has also been evident in extrapulmonary sites including meningitis. When progressive disease occurs, most patients already have low CD4 lymphocyte counts. In such cases, effective therapies have included amphotericin B, ketoconazole, and newer investigational agents such as itraconazole, and fluconazole. Although coccidioidal infections have developed in only a few patients away from the endemic regions, those that have suggest that reactivation is possible. PMID- 2247711 TI - Fungal diseases. Introduction. PMID- 2247712 TI - Histoplasmosis: update 1989. AB - Histoplasmosis is a relatively mature disease that was first described 85 years ago. Histoplasmosis was long thought to be a rare and uniformly fatal illness. However, widespread use of skin testing in the 1940s proved that it was a common infection, especially in the central United States, and almost invariably benign. Primary histoplasmosis often presents as a self-limited, nonspecific respiratory infection, and thus, it was realized that a huge iceberg of subclinical and mildly symptomatic cases had been missed for years, since only the highly symptomatic and progressive infections had been diagnosed. Once the disease was recognized as a common one, many new clinical forms of the illness were recognized, including diffuse infiltrates due to heavy exposure, chronic cavitary disease resembling tuberculosis, and complications of primary infection, including mediastinal granuloma and the superior vena caval syndrome. Despite the mature state of histoplasmosis, it is still a disease capable of producing surprises. In this article, the history of histoplasmosis is reviewed, as well as current major concepts about the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this infection. Newer developments are then highlighted using the same outline. PMID- 2247713 TI - Factorial designs for crossover clinical trials. AB - When measuring the joint effect of two factors it is advantageous to use a factorial design. If the application is suitable, efficiency may be further improved by using a crossover design. This paper presents a flexible method for amalgamating these two devices. Designs are constructed from smaller designs, known as bricks, generated cyclically from tabulated initial sequences. The bricks have known efficiencies for estimation of direct treatment main effects and interactions; the efficiencies can be simply combined to approximate the efficiencies of the whole design. This allows the user to build a design that is tailored to the particular objectives of the experiment. Three and four periods, and two factors with up to four levels are considered. PMID- 2247714 TI - Model selection and the estimation of odds ratios in the presence of extraneous factors. AB - This paper deals with model selection and the estimation of odds ratios from cross-classified frequencies in the presence of extraneous factors. The odds ratio is estimated in different ways dependent on whether the extraneous factor is modelled as an effect modifier, a confounder, or neither. Routinely this choice is based on statistical tests of null hypotheses. By contrast, we propose selection of the model which is estimated to maximize the accuracy of the estimator of the odds ratio, on average. We demonstrate how a non-parametric bootstrap method can be used to carry out the selection, and illustrate the methodology using an example on use of oral contraceptives and myocardial infarction. PMID- 2247715 TI - Symmetry and quasi-symmetry: an example in modelling pairs of sounds from children's early speech. AB - The models of symmetry and quasi-symmetry may have use in the analysis of categorical data in square tables where the row and column classifications are the same. Under the model of symmetry, the probability that an observation falls in, say, the (i,j) cell of a square table is the same as the probability that it falls in the (j,i) cell. The model of symmetry requires that the expected marginal total for any one row of the table be the same as the expected marginal total for the corresponding column. The model of quasi-symmetry, which is a generalization of the model of symmetry, does not require this equality of expected row and column totals. In this paper, we illustrate the use of the models of symmetry and quasi-symmetry in the analysis of categorical data that summarize pairs of sounds in infants' and toddlers' early utterances. In the past, the complexity of infants' early vocalizations has been difficult to measure because of a lack of methods to quantify prelinguistic phonetic variables. We use the models of symmetry and quasi-symmetry as a first attempt to quantify the complexity of infants' early speech. We hope that the discovery of models appropriate for quantification of language development in normal children will have later use in identification of children at risk for communicative disorders. PMID- 2247716 TI - A comparison of Poisson regression models fitted to multiway summary tables and Cox's survival model using data from a blood pressure screening in the city of Bergen, Norway. AB - Multiplicative models for the association between blood pressure and coronary heart disease mortality in 5201 men aged 40-49 years at time of examination were compared. Piecewise exponential models fitted to summary tables formed by cross classification by three systolic and three diastolic blood pressure groups, two age groups and three time intervals gave results close to the Cox model for continuous data. The parametric integrated baseline hazard functions estimated from grouped data were close to Breslow's nonparametric estimate in the Cox model. PMID- 2247717 TI - A note on point estimation of the hazard ratio in exponential distributions. AB - The maximum likelihood estimator (MLE) of the ratio of the hazard rates in two exponential distributions is biased. This bias can be important when sample sizes are small or the ratio of these two hazard rates is large. When there is either no censoring or type II censoring, we propose using the uniformly minimum variance unbiased estimator (UMVUE). We show that using the UMVUE instead of the MLE reduces the mean-squared error (MSE). We have found that the UMVUE always has MSEs smaller than the MLE. We have also found that the UMVUE leads to important reductions in the MSE when the sample size used to calculate the hazard rate in the numerator of the hazard ratio is small (say less than or equal to 20) regardless of the sample size in the denominator. In the presence of type I censoring, the proposed estimator and the MLE are both biased. On the basis of a Monte Carlo study, however, we obtain similar reductions in the MSE using the UMVUE, as for no censoring or type II censoring. PMID- 2247718 TI - Estimating correlation between alternative measures of disease progression in a longitudinal study. Modification of Diet in Renal Disease Study. AB - A primary outcome variable in longitudinal studies is often the rate of change of a continuous measurement over time. Examples include the one-second forced expiratory volume (FEV1) in pulmonary studies or glomerular filtration rate (GFR) in renal studies. An individual patient's least-squares estimate of slope obtained from a linear regression is an imprecise measure of the true slope for that patient, and correlations involving the estimated slopes will be biased due to this measurement error. This paper presents methods for estimating the true correlation between these imprecise slope estimates, or between slope estimates and other variables measured with error. In addition to providing a simple consistent estimator of the correlation, we show how the maximum likelihood estimate of the correlation coefficient and a 100(1 - alpha) per cent confidence interval can be obtained. An example estimating the correlation between GFR and inverse serum creatinine slopes in patients with chronic renal disease is given. PMID- 2247719 TI - Prognostic scores for detecting a high risk group: estimating the sensitivity when applied to new data. AB - The sensitivity of a prognostic scoring system will tend to be exaggerated if the scoring system is both derived and validated on the same data. This paper provides, by analogy to regression with error in an explanatory variable, an intuitive basis for the methodological results of Copas which seek to estimate the degree of such exaggeration. There was good agreement between Copas' results and those achieved in a series of cross-validation exercises where logistic regression models predicting the risk of ischaemic heart disease were derived using data from the prospective British Regional Heart Study. When truly important variables were included, the exaggeration of the sensitivity increased as the number of cases of disease available decreased. It is concluded that Copas' method, which is easy to implement in practice, may be helpful in realistically anticipating the extent of such exaggeration, and that it can be usefully employed before pursuing a scoring system on newly collected data. PMID- 2247720 TI - Variation in heart disease mortality across census tracts as a function of overdispersion and social class mixture. AB - Variation in heart disease (HD) mortality rates across census tracts is greater than expected given binomial error and available explanatory variables. We extended an extra-binomial variation model for rates standardized by the direct method. The overdispersion parameter accounted for 36 per cent of the observed variation in standardized rates. Ignoring overdispersion resulted in a change in an estimate of the effect of social class on HD mortality and substantial underestimation of the error of the estimates of such effects. Ecologic regression on the proportional mixture of social classes within tracts provided an appealing approach to the problem of estimating fixed effects with aggregated data. PMID- 2247721 TI - Estimation of parasitic infection dynamics when detectability is imperfect. AB - The simultaneous estimation of infection rate, cure rate and detectability of parasitic infections is considered. A new method for this estimation based on a simple statistical model assuming constant transition rates between parasite states is proposed. Repeated observations on the infection status of the same individuals is required for this method. A maximum likelihood approach is used for parameter estimation and the calculation of standard errors of the estimates. The method is illustrated by a longitudinal study of the presence of Giardia lamblia infection in Kenyan children. PMID- 2247722 TI - Survival analysis in natural history studies of disease. PMID- 2247723 TI - Bioelectrical impedance analysis to determine fat-free mass, total body water and body fat. PMID- 2247726 TI - Developmental aspects of physiological function relating to aerobic exercise in children. AB - The many physiological determinants of exercise performance mature throughout the childhood years. Current research suggests that the improvements in maximal aerobic power which occur as the child ages are an expression of both increased body size and improved function. Absolute VO2max increases during the childhood years in both girls and boys. Average VO2max related to bodyweight, however, remains stable in boys of all ages, while values in girls decline progressively as they grow. VO2 at a given treadmill speed or slope falls during the growing years. This improvement in running economy may explain parallel advances in endurance exercise performance. The explanation for greater running economy with growth is uncertain, but lower step rate, improved running mechanics, and changes in body mass: surface area ratio may play a role. PMID- 2247724 TI - Physical exercise and menstrual cycle alterations. What are the mechanisms? AB - The prevalence of menstrual cycle alterations in athletes is considerably higher than in sedentary controls. There appears to be a multicausal aetiology, which makes it extremely difficult to dissociate the effects of physical exercise on the menstrual cycle from the other predisposing factors. From cross-sectional studies it appeared that physical training eventually might lead to shortening of the luteal phase and secondary amenorrhoea. Prospective studies in both trained and previously untrained women have shown that the amount and/or the intensity of exercise has to exceed a certain limit in order to elicit this phenomenon. We hypothesise, therefore, that apart from a certain predisposition, athletes with a training-induced altered menstrual cycle are overreached (short term overtraining, which is reversible in days to weeks after training reduction). Menstrual cycle alterations are most likely caused by subtle changes in the episodic secretion pattern of luteinising hormone (LH) as have been found in sedentary women with hypothalamic amenorrhoea as well as in athletes after very demanding training. The altered LH secretion then, might be caused by an increased corticotrophin-releasing hormone (CRH) secretion which inhibits the gonadotrophin-releasing hormone (GnRH) release. In addition, increased CRH tone will lead to increased beta-endorphin levels which will also inhibit the GnRH signaller. Finally, the continuous activation of the adrenals will result in a higher catecholamine production, which may be converted to catecholestrogens. These compounds are known to be potent inhibitors of GnRH secretion. In conclusion, menstrual cycle alterations are likely to occur after very demanding training, which causes an increase secretion of antireproductive hormones. These hormones can inhibit the normal pulsatile secretion pattern of the gonadotrophins. PMID- 2247727 TI - Use of telethermography in the management of sports injuries. AB - Telethermography can contribute to the diagnostic process in the management of sports injuries by clearly demonstrating thermal alterations in the tissues involved. Although there are no typical images, in general hyperthermic images are found when inflammatory reactions prevail, and hypothermic pictures when compression or degenerative processes are present. Telethermography is not only an aid to diagnosis, it also appears to be an ideal tool in controlling the injury evolution and treatment efficacy. In fact this objective method of evaluation is noninvasive, innocuous and repeatable, and well-related to the clinical and functional status. PMID- 2247729 TI - [Dentists and the prevention of oral cancer]. AB - The authors, after participating on the European Conference on Dentists and Cancer Prevention, part of the program Europe Against Cancer, describe the main conclusions of the working groups, namelly on epidemiology and etiology of oral cancer, participation of dentists on community based programs for primary and secondary prevention of pre-cancer and cancer, as well as the curriculum changes proposed for Dental degree and the role of continuous education and of dental societies in this field. PMID- 2247725 TI - Biochemical mechanisms for oxygen free radical formation during exercise. AB - The biochemical mechanisms behind skeletal muscle soreness and damage with muscular overuse have remained unclear. Recently, however, a growing amount of evidence indicates that free radicals play an important role as mediators of skeletal muscle damage and inflammation. During exercise, two of the potentially harmful free radical generating sources are semiquinone in the mitochondria and xanthine oxidase in the capillary endothelial cells. During high intensity exercise the flow of oxygen through the skeletal muscle cells is greatly increased at the same time as the rate of ATP utilisation exceeds the rate of ATP generation. The metabolic stress in the cells causes several biochemical changes to occur, resulting in a markedly enhanced rate of production of oxygen free radicals from semiquinone and xanthine oxidase. During normal conditions free radicals are generated at a low rate and subsequently taken care of by the well developed scavenger and antioxidant systems. However, a greatly increased rate of free radical production may exceed the capacity of the cellular defence system. Consequently, a substantial attack of free radicals on the cell membranes may lead to a loss of cell viability and to cell necrosis and could initiate the skeletal muscle damage and inflammation caused by exhaustive exercise. PMID- 2247728 TI - Triceps brachii injuries. AB - Triceps brachii injuries are uncommon, resulting from indirect or direct trauma generally associated with an eccentric contraction. The tendo-osseous junction is the most common location. An extensor lag and palpable gap are diagnostic of complete rupture. Diminished extension strength against resistance implies a partial triceps rupture. A radiograph must be obtained as triceps ruptures are associated with olecranon or radial head fractures. A lateral radiograph may reveal an avulsion or 'flake' fracture. Early surgical repair of complete tendon ruptures is recommended. Surgical results are generally excellent. PMID- 2247730 TI - [Mouth opening limitation from hypertrophy of the coronoid apophysis]. AB - Bilateral generalized enlargement of the coronoid processes is an unusual and rarely reported condition. In the presented case the alleviation of restriction in mandibular movement was only dependent on bilateral coronoidectomies. There is a need for clarification of the condition regarding cause, diagnosis and probably terminology as well as possible relationship to osteochondroma of the coronoid processes. PMID- 2247731 TI - [Conference on psychosomatic manifestations in the oral cavity]. PMID- 2247733 TI - Actinobacillus actinomycetemcomitans and black-pigmented bacteroides in advanced periodontitis in man. Theoretical and practical considerations. PMID- 2247732 TI - [Fluoride--"state of the art"]. PMID- 2247734 TI - [The repair process in tooth extraction wounds after implantation of microcrystalline collagen fragments. Histological study in rats]. AB - The author studied histologically, the healing process after dental extraction in rats which sockets were filled with fragments of microcrystalline collagen. Thirty six rats (Rattus Novergicus, albinus, Wistar), young, male, weighting from 90 to 110 g and separated into two groups, control and experimental, of eighteen animal each. All animals were anaesthetized with 10% cloral hidrate, 3 ml/Kg body weight and the right maxillary incisors were extracted. In control animal the sockets were sutured after clot filling, and the experimental sockets were sutured after filling with microcrystalline collagen. Three animals of each group were killed after periods of 1, 3, 6, 14, 21 and 24 days after surgery. The following conclusions were drawn: 1. Microcrystalline collagen caused an evident inflammatory reaction in the inicial phases of the healing process of the sockets. 2. Microcrystalline collagen was biodegraded 6 to 14 days after surgery. 3. Microcrystalline collagen delayed the repair process of the sockets. PMID- 2247735 TI - [The prevention of dog bites]. PMID- 2247736 TI - [Team work in cardiac arrest]. PMID- 2247737 TI - [Health problems and health priorities in Spain. Reflexions for a current debate]. PMID- 2247738 TI - [Continuing education and health professionals]. PMID- 2247739 TI - [New prospects for Spanish nurses interested in continuing their education abroad. The Certificate of Nursing Sciences: the Clinical Environment at the University of Montreal. Interview by M. J. Nadal and B. Sune]. PMID- 2247740 TI - [The participation of the user in the improvement of health services. An opinion poll conducted at the Nuestra Senora de Sonsoles Hospital of INSALUD in Avila]. PMID- 2247741 TI - [Irrigation of the colostomy]. PMID- 2247742 TI - [Shorter dialysis with paired filtration dialysis]. PMID- 2247743 TI - [Home visits. What does the population think?]. PMID- 2247744 TI - [Human resources in nursing. The management prospects]. PMID- 2247745 TI - [The oximeter]. PMID- 2247746 TI - [Continuing education. 52. Subject: statistics. Topic: the concepts of statistics]. PMID- 2247747 TI - [The contradictory dichotomy between education and professional practice]. PMID- 2247748 TI - [Carotid stenosis and obliteration of the contralateral carotid. A prospective study of the risks of a carotid endarterectomy intervention and its long-term results]. AB - From March 1980 to July 1988 a consecutive series of 256 patients (p.) underwent 301 carotid endarterectomy + patch with routine use of continuous intraoperative EEG monitoring and selective use of an intraluminal shunt (IS) for the presence of an atherosclerotic plaque concerning the internal carotid artery (ICA). Patients were divided in two groups: the first (42 p.) marked by contralateral ICA occlusion, the second (214 p.) without contralateral ICA occlusion (259 CEA). Immediate peroperative, long term and global (immediate and long term) outcomes were prospectively and comparatively studied. A temporary IS was inserted in 27 p. (64%) of the group I and in 38 p. (14%) of the group II. Immediate permanent postoperative neurological deficit occurred in 1 p. of group I (2.38%) and in 2 p. (0.9%) in group II. Immediate postoperative mortality was 0% and 0.9% in group I and II respectively. All p. had neurological valuation and Echo-Doppler of operated ICA and of the contralateral ICA every 6 months (middle follow-up 44 months). New neurological symptoms compared in 5.8% of p. of group I and in 5.23% of p. of group II with a stroke rate of 0% and 2.32% respectively. There were 2 restenosis of operated ICA, both of them in p. of group I, that underwent reoperation. In the two groups the principal causes of deaths were myocardial infarct and cancer; in the group I no death was due to stroke versus 1.86% in the group II. PMID- 2247749 TI - Imitating gesture learning in apraxic patients. AB - The authors studied a group of patients with ideomotor apraxia (IMA) to verify if these patients had some difficulties in gesture learning task in respect to non apraxic patients and normal control subjects. The results show that learning difficulties are present in patients with IMA. Apraxic patients are not able to perform the gestures in the testing situation and non in everyday life; this fact would demonstrate that the motor pattern still exists in these patients but is inaccessible unless elicited by a strong stimulation. PMID- 2247751 TI - [The combined use of instrumental and laboratory examinations in multiple sclerosis: is the diagnostic facilitation real?]. AB - Spatial-temporal dissemination of neurological signs is an essential criterion for establishing a definite diagnosis of Multiple Sclerosis (MS). Unfortunately, we often observe patients who present a history consistent with MS but without objectivity indicating the presence of at least two or more distinct lesions of Central Nervous System (CNS). In recent years, many Authors have emphasized the use of Multimodal Evoked Responses (MER), Cerebrospinal Fluid (CSF) analysis for the research of Oligoclonal Bands (OB), and Magnetic Resonance Imaging (MRI) as highly sensitive techniques for demonstrating the spreading of the lesions. This study, carried out to evaluate whether the combined use of these three methods would increase the diagnostic MS sensitivity, comprises 62 patients classified in Definite (n = 24). Probable (n = 18) and Possible (n = 20) MS according to the clinical criteria of McAlpine. All our cases fulfilled a complete ER evaluation (VER, SER, BAER), a paired CSF and serum Isoelectric focusing (IEF) and a cerebral MRI. Moreover, IgG Index was also estimated. CSF IEF was the most sensitive test in Definite (91.7%) and Possible (80.0%) MS, nearly followed by MRI (87.5% and 45.0% respectively). VER (87.5% and 60.0%) and SER (87.5% and 65.0%). On the contrary, MRI showed the higher sensitivity in Probable MS (94.4%). The course of the disease influenced only SER and VER in all diagnostic group, while the duration correlated positively with BAER and VER. Only VER and BAER, finally, supplied additional information about the not revealed clinically or by MRI CNS disorders. Thus, our data further emphasize the value of combining these laboratory tests for establishing an early and more accurate diagnosis of MS. PMID- 2247750 TI - Hyperbaric oxygen therapy in the treatment of multiple sclerosis. A clinical and electrophysiological study in a 2 year follow-up. AB - 15 patients with chronic progressive Multiple Sclerosis were treated with Hyperbaric Oxygen Therapy at 2.0 atmospheres absolute for a total of 20 daily exposures followed by 2 exposures every month. The treatment was carried out for a 24 months follow-up. No objective benefit resulted from Hyperbaric Oxygen Therapy at the completion of the study while a subjective improvement in bladder control was reported in the short and in the long-term follow-up by 8 and by 5 patients respectively. No significant variations in the electrophysiological results were observed after the first 20 consecutive exposures. It is concluded from this trial that a long-term Hyperbaric Oxygen Treatment cannot moderate the progression of Multiple Sclerosis. However, an improvement in the quality of life can be obtained in some patients resulting from a better control of bladder function. PMID- 2247752 TI - Adult onset of subacute sclerosing panencephalitis: a case report. AB - A new case of subacute sclerosing panencephalitis with onset in adult life is reported. Clinical picture was characterized by a maculopathy, followed two years after by behavioural disturbances, psychomotor impairment, pyramidal signs and left-side myelonic jerks synchronously with the typical periodic R-complex in the EEG. CT-scan and MRI showed a wide demyelinative lesion in the right temporo occipital area of the brain. Elevated antibody titers to measles virus in serum and CSF were present. Death occurred within 6 months while in coma. The neuropathologic findings confirmed the diagnosis of SSPE revealing widespread inflammatory lesions in the grey and white matter areas of demyelinization more evident in the right temporo-occipital regions and several Cowdry type A inclusions in glial cells and neurons. PMID- 2247753 TI - Molecular pathology of chronic myelogenous leukemia. AB - The presence of Philadelphia chromosome t(9:22) is a hallmark of 95% of clinical cases of chronic myelogenous leukemia (CML) as well as 20% of adult acute lymphoblastic leukemia (ALL) and 5% of acute myeloid leukemia (AML). The product of t(9;22) is a fusion protein BCR-ABL. The fusion proteins of CML, ALL and AML have increased tyrosine kinase activity and show a transforming potential in vitro and in animal models. The shorter p190 protein is associated almost only with ALL and AML, while the protein p210 is present in both chronic phase and blast crisis of CML and also in 50% of Philadelphia-positive (Ph1+) ALL. In CML the transition from chronic phase to blast crisis is usually accompanied by additional genetic events, e.g. additional chromosomal abnormalities, and oncogene activation(s). The detailed understanding of molecular basis of CML, and Ph1+ ALL and AML provides highly sensitive molecular and serological methods to complement classical cytogenetics. The advantages and limitations of these techniques are described and discussed below. PMID- 2247754 TI - Chromosome abnormalities in chronic myeloid leukaemia. A model for acquired chromosome changes in haematological malignancy. AB - The last decade has been very exciting for cancer cytogeneticists. At the start of the decade, the role of cytogenetics in clinical medicine was still unclear. Many felt that such investigations were largely of academic interest. Today, cytogenetic investigations are considered essential in many cancers, where they contribute in diagnosis, staging, choice of therapeutic protocol, and monitoring of the effects of therapy. The number of primary chromosome changes in human cancer exceeds 100, and while the majority of these changes are associated with haematological malignancies, the contribution from the solid tumours is now growing rapidly. Closer ties between scientists and physicians involved in laboratory and clinical medicine have resulted in the emergence of many well defined cytogenetic-clinicopathological entities. With the advances in molecular biology that characterized the 1980s came the disappearance of all scepticism about the critical role played by chromosome change in oncogenesis. To date, we have learned more about the details of cancer biology in chronic myeloid leukaemia and the lymphoid malignancies through the molecular dissection of primary chromosome changes than through any other approach. Further studies will, no doubt, lead us to an understanding of the molecular basis of many of the primary and secondary chromosome changes that are non-randomly acquired in human cancer. PMID- 2247755 TI - Oncogene involvement in myelodysplasia and acute myeloid leukemia. AB - The clonal malignancies of acute myeloid leukemia and the myelodysplastic syndromes are associated with numerous chromosomal and oncogenic abnormalities. Activation of oncogenes has been demonstrated, although there is little evidence that this alone causes malignant transformation of diploid cells as a consequence. Patterns of abnormalities can be seen as the patient progresses from myelodysplastic syndrome to acute myeloid leukemia, but no unique or invariant findings have been described. Chromosomal changes, with the exception of some translocations, are neither disease nor lineage specific. At this time the data provide good support for the multistep view of carcinogenesis, and there is indirect or circumstantial evidence for the presence of tumor suppressor genes on 5q and 7q. The continued study of these clonal hematological disorders will provide considerable insight into mechanisms of tumorigenesis and possibly may lead to new modes of therapy, for example, through altering the microenvironment, interfering with deranged signal transmission, or introducing antioncogenes. PMID- 2247756 TI - T cell receptor and immunoglobulin genes in hematologic malignancies. AB - In this review, we discuss the structure, organization and activation of the immunoglobulin (Ig) and T cell receptor (TCR) genes and the use of DNA probes derived from these genes as tools to determine clonality and cell lineage in hemopoietic malignancies. We also examined briefly the participation of immunoglobulin and TCR genes in chromosomal aberrations present in many lymphoproliferative disorders, often involving protooncogenes and potentially of tumorigenic consequences. PMID- 2247757 TI - Oncogene involvement in lymphoid malignancy. AB - Several nonrandom chromosomal translocations that occur in T and B cell malignancy have been shown to involve the juxtaposition of a putative proto oncogene and one of the antigen receptor genes. Cloning studies of several of these breakpoints have helped to elucidate the structural basis of some of these chromosomal translocations as well as the molecular characteristics of some of the proto-oncogenes. One of the most studied proto-oncogenes is BCL2, frequently involved in a translocation in B cell lymphomas. Several biological studies of the expression of this proto-oncogene in cell lines and/or transgenic mice have shown that it is one of the factors which can induce lymphoid proliferation and may thus be an important etiologic factor in the generation of B cell lymphoma. Cloning studies of these chromosomal breakpoints have led to the application of molecular genetic techniques for the diagnosis and detection of expression of these proto-oncogenes. Further study of these oncogenes is required to establish their role in tumorigenesis and their usefulness in clinical practice. PMID- 2247758 TI - [The anatomy of the pelvis]. AB - The pelvis consists of the sacrum, the ossa coxae, and additionally the ligaments between these bones. According to mathematical calculations the bony structure as well as the arrangement of ligaments result in optimal engineering principles, i.e. maximal strength is achieved by minimal principles, i.e. maximal strength is achieved by minimal material. The muscles inside the pelvis are covered by a fascial layer. The latter represents a continuation of the abdominal transversal fascia which extends to the pelvic floor. The connective tissue fibres around the pelvic viscera interweave with those of the pelvic floor and laterally with the connective tissue around vessels and nerves. Connective tissue around the neurovascular sheaths is nearly transversely arranged and forms the lateral ligaments of bladder, uterus or prostate gland and the rectum. Several vertically arranged connective tissue ligaments accompany either the superior rectal artery and hypogastric nerves or the ureter and the ovarian vessels. Therefore, the lymphatic fluid of the pelvic organs passes the aortic lymph nodes and/or to the lateral pelvic wall along the branches of the internal iliac vessels. PMID- 2247759 TI - [Clinical aspects and requirements of radiology from the point of view of gynecology]. AB - For primary diagnostics and the follow-up of gynaecological diseases, inspection with colposcopy and palpation play the most important role. Ultrasound techniques provide the most essential complementary method. Computed tomography is not helpful for the pretherapeutic staging of gynaecological cancer. This is especially true of the staging of cervical cancer especially for the lymph-node diagnosis. The same is the case in the diagnosis of recurrences. The uncertainty of all diagnostic procedures--the clinical and imaging techniques--very often leads to indications for staging operations. PMID- 2247760 TI - [Possibilities and limitations of radiology--CT and MRT in cases of tumors of the uterus and ovary]. AB - The author describes the present possibilities of computed tomography (CT) and of magnetic resonance (MR) tomography. MR is superior to CT in the visualisation of carcinomas of the cervix and endometrium, especially in the initial stages, whereas in the diagnosis of the spread of tumours (especially the advanced ones) CT yields results similar to those of MR. In carcinoma of the ovary, however, MR has so far not proved to be definitely superior to CT despite the multiplanar visualisation possibilities it offers. It is in fact inferior to CT especially in clarifying the extent of extrapelvic spread. In posttherapeutic diagnostics MR explores new avenues in respect of delineation between scar and recurrence, as initial investigations have shown. PMID- 2247761 TI - [Computed tomography and magnetic resonance tomography in cases of pelvic tumors unconnected with organs]. AB - Computed tomography (CT) will remain the method of choice in cases of parapelvic masses. It allows to identify the extent and the relationship of the mass to the neighbouring structures. Some cases serve to point out the utility of CT in demonstrating findings useful in distinguishing various types of tumours. MRT is compared to CT in visualizing the contrast between tumour and bone marrow as well as surrounding soft tissues, especially muscle. Furthermore, MRT may be helpful in early detection of the cartilage cap of an osseous mass and tumour recurrence. PMID- 2247762 TI - [Computed tomography and magnetic resonance tomography of rectal and sigmoid tumors]. AB - CT and MR imaging are of minor importance for the preoperative diagnosis of rectosigmoid carcinoma. A synchronous colon tumor can be excluded with a barium enema, while an accurate diagnosis of liver metastases is possible using real time ultrasonography. However, post-operative management requires the use of tomographic methods: MR imaging has proved to be more accurate than CT for differentiation between local recurrence and post-operative scars. Therefore MRI should be the method of choice after surgery for rectosigmoid carcinoma in all patients without postoperative baseline examinations. PMID- 2247763 TI - [Indications and applicability of sonography or endosonography in cases of diseases of the bladder and prostate]. PMID- 2247764 TI - [A comparison of conventional tomography and computed tomography in cases of diseases of the sacroiliac joint]. AB - 16 patients with diseases of the sacroiliac joints were examined both with computer tomography and with conventional tomography. Both techniques were characterized by a high sensitivity. Computer tomography was superior in exactly delineating the extent of the pathologic changes. In conventional tomography the joint surface was more blurred, erosions were larger, and signs of ankylosis were more expanded, so that the joints seemed to be more altered in 8 cases than demonstrated by computer tomography. Very accurate changes like subchondral cysts were recognized only in the computer tomograms. In all cases in which anteroposterior radiographs revealed no clear result, the authors recommend to additionally employ computer tomography. PMID- 2247765 TI - Distribution of bronchoalveolar cells and fibronectin levels in bronchoalveolar lavage fluids from patients with lung disorders. AB - Differential cell counts and fibronectin levels were recorded in bronchoalveolar lavage fluids (BALF) from patients with lung cancer, idiopathic pulmonary fibrosis (IPF), sarcoidosis, pneumonia, acquired immunodeficiency syndrome (AIDS), and chronic obstructive lung disease (COLD). In all groups fibronectin levels were significantly higher than in the control group; patients with sarcoidosis had a six-fold higher fibronectin level (mean values), AIDS 5.4-fold, pneumonia 4.4-fold, lung cancer, IPF and COLD 2.4-3.0-fold. In control smokers the fibronectin level was significantly higher compared to healthy nonsmokers (p less than 0.002). The increased fibronectin levels could not be explained by contamination of BALF with blood or leakage of plasma proteins. Thus, increased fibronectin levels probably reflect local (e.g. macrophage/fibroblast) synthesis. PMID- 2247766 TI - The intracellular distribution of cobalt in exposed and unexposed rat myocardium. AB - The intracellular distribution of cobalt was analysed in the myocardium of exposed and unexposed rats. The exposed rats were given a dietary cobalt supplementation of 40 mg CoSO4.7 H2O/kg body weight for 8 weeks. The mitochondrial fraction showed the greatest relative increase in cobalt: 0.09 ng/mg protein in the unexposed rats to 8.43 ng/mg protein in the exposed rats. In the exposed rats the submitochondrial particles had the highest levels of cobalt: 19.43 ng/mg protein, followed by the sarcoplasmatic reticulum: 12.3 ng/mg protein. The microsomal 44,000 g supernatant also showed an increase, although the levels remained low (0.51 ng/mg protein in the exposed animals). Apparently the calcium-storing organelles had the highest levels of cobalt. This could affect calcium flux in myocardial cells and, secondarily, tension development in cardiac muscle. PMID- 2247767 TI - Effect of enalapril on haemoglobin and serum erythropoietin in patients with chronic nephropathy. AB - It has been suggested that angiotensin-converting enzyme (ACE) inhibitors halt the progression of chronic renal failure. During the first months of a controlled trial of this hypothesis a fall in haemoglobin (Hb) was observed in patients treated with the ACE inhibitor enalapril. It was investigated whether this was related to changes in serum erythropoietin (EPO). Data were analysed in 59 consecutive patients during an observation period of 90 days. In enalapril treated patients (n = 27) Hb fell gradually from a median value of 7.6 to 6.7 mmol/l at 90 days of treatment. In the control group of patients on conventional antihypertensive treatment (n = 32) median Hb was unchanged (7.6 mmol/l) throughout the observation period (p less than 0.001 enalapril vs control). In the enalapril-treated group median EPO concentration fell from 32 to 24 U/l at 90 days of treatment, whereas in conventionally treated patients median EPO was 34 U/l and 35 U/l, respectively (p less than 0.05 enalapril vs control). Neither glomerular filtration rate nor arterial blood pressure differed significantly in the two groups. Furthermore, there were no signs of bone marrow suppression, increased haemolysis or change in plasma volume. In conclusion, a decrease in Hb was found after start of treatment with enalapril in patients with progressive chronic renal failure, possibly caused by a suppression of EPO production. PMID- 2247769 TI - Automated cyanide-free method for haemoglobin determination on Technicon H.1. AB - We have developed a cyanide-free haemoglobin method for our Technicon H.1 counter. By adding 2.5 mmol/l of the ionic surfactant sodium dodecyl sulphate in 154 mmol/l sodium chloride, the haemoglobins are converted to a stable product, denatured globin haemichrome, within the 25 s available on the instrument. The method is as precise and accurate as the original H.1 method, and the reagent is easily made in the laboratory at a very low price. Since the method is relatively safe with regard to waste disposal, the effluent from the counter can be drained into the laboratory sink. The method, a 'SDS-haemichrome method', has now worked very satisfactorily in routine use for a year. Manufacturers of haematological analysers should consider this haemoglobin method for their automated instruments. PMID- 2247768 TI - Diurnal and monthly intra-individual variability of the concentration of lipids, lipoproteins and apoproteins. AB - Diurnal and monthly variability of the serum concentration of lipids, lipoproteins and apoproteins were examined in 11 healthy subjects aged 32-63 (mean 46) years. For diurnal measurements, blood samples were drawn at 0800, 1200, 1500, 1800, and 2100 hours. The variability over 1 month was assessed from four analyses taken weekly at 0800 hours after at least 8 h fast. The analytical variability expressed as mean coefficient of variation (CV) ranged from 0.95% for cholesterol to 7.6% for apoprotein B. The mean CVs for diurnal biological variability were 2.4% for cholesterol, 3.5% for HDL-cholesterol, 5.1% for LDL cholesterol, 29.5% for triglycerides, 6.5% for apoprotein A and 6.5% for apoprotein B. The respective biological CVs for monthly variability were 4.2%, 4.1%, 5.2%, 20.7%, 9.4% and 9.7%. A repeated-measures ANOVA revealed a significant increase of triglycerides (p less than 0.01) and decrease of LDL cholesterol (p less than 0.01) during the day. Within 1 month, apoprotein A tended to rise (0.05 less than p less than 0.10). Although the best reproducibility was found for cholesterol, the results obtained indicate that six tests have to be taken before and after intervention by drug or diet to detect a reduction of 10% in an individual with a probability of 0.95. PMID- 2247770 TI - Plasma osteocalcin: biological variations and reference limits. AB - Osteocalcin, the most abundant non-collagenous protein in the bone matrix, is partly released in blood. We have measured its concentration by a radio immunoassay procedure in 1096 apparently healthy subjects from both sexes who came for a health screening examination. Their ages varied from 4 years to over 65 years. Venous blood was drawn in the morning from fasting subjects. Plasma osteocalcin was higher in men than in women. Its level increased significantly with age, body weight, height and bone age until age 12-13 years in girls and 14 15 years in boys. In women, osteocalcin level increased after the age of 50 years and was higher than in men. It remained constant over age 60 years in both sexes, but was higher in women. There was no effect of menstrual cycle in girls at puberty. Plasma osteocalcin did not vary with follicular and luteal phases or with the use of oral contraceptive drugs in women. The usual nonsteroid anti inflammatory drugs had no effect on blood osteocalcin level. Reference limits according to age and sex are provided. PMID- 2247771 TI - Quantitative buffy coat analysis in haematological patients compared to standard laboratory methods. AB - We have tested a Quantitative Buffy Coat (QBC) instrument (Becton Dickinson, USA), and compared results obtained with this instrument to results obtained with standard methods in a haematology clinic. The basic principle of the method is a classical haematocrit centrifuge. The analysis provides a haematocrit value, platelet count, a total white blood count, and separates the white blood cells in granulocytes and mononuclear cells (lymphocytes plus monocytes). The instrument is easy to use but requires a trained observer. All results are available in 15 min. We have found the accuracy of the method good for all parameters. The precision of the instrument is good but for estimation of granulocytes and lymphocytes plus monocytes we did not find the high sensitivity claimed by the manufacturer (manufacturer's lower limit 0.02 x 10(9)/l; standard deviation for low levels of granulocytes: 0.300 x 10(9)/l and lymphocytes plus monocytes: 0.235 x 10(9)/l). A large fraction of samples (leukocytes 27%, platelets 40%) from a haematological clinic falls beyond the limits for reliable results set by the manufacturer, which reduces the utility of the instrument in such patients. Furthermore, in 21% and 10% of samples within the recommended range for leukocytes and platelets, respectively, QBC results could not be read owing to ill-defined boundaries. For granulocytes and lymphocytes plus monocytes 25% and 34% of the samples, respectively, could not be read owing to ill-defined boundaries. The instrument is not constructed to protect against blood contamination of the centrifuge and, therefore, the safety of the instrument is not satisfactory. PMID- 2247773 TI - Correlations between psychological and physiological responses to acute flight phobia stress. AB - Exposure of phobic subjects to real-life psychological stress may induce a high level of anxiety and be better than laboratory experiments for studies of physiological responses to psychological stress in human research. Therefore, by introducing natural psychological stress, i.e. actual flying in subjects with flight phobia (n = 23), the present study aimed at testing the hypothesis that there is, during mental stress, a direct relationship between the level of anxiety and the responses in the physiological variables blood pressure, heart rate and plasma catecholamines. Plasma adrenaline, heart rate, blood pressure and perceived anxiety measured by three different scales increased highly significantly during flight whereas plasma noradrenaline did not change. No direct relationship was found between the physiological and psychological variables. Thus, the physiological responses to natural psychological stress in terms of phobic anxiety may be definite, but the way the responses are related is less clear. PMID- 2247772 TI - Ultrafiltration devices tested for use in a free thyroxine assay validated by comparison with equilibrium dialysis. AB - A new ultrafiltration method for measuring serum free thyroxine (FT4) is presented. The method makes use of disposable ultrafiltration devices, which were selected on grounds of their ability to produce protein-free serum ultrafiltrates necessary for accurate determination of FT4. Ultrafiltrate thyroxine was measured by radio-immunoassay. As measured by this method, the mean serum FT4 concentration in reference subjects (n = 17) was 25.4 pmol/l (SD 7.8). Two patient groups were studied: hyperthyroid (n = 20, mean serum FT4 138 pmol/l, SD 69) and hypothyroid (n = 18, mean serum FT4 14.8 pmol/l, SD 6.5). These results were compared with serum FT4 concentrations, as measured by an ultrafiltration method based on the use of dialysis-tubing bags (r = 0.97), and by an equilibrium dialysis method (r = 0.95). The mean level of FT4, as measured by the ultrafiltration methodologies, was about twice as high as that measured by equilibrium dialysis. This new FT4 method is more practical than earlier ultrafiltration methods and, theoretically, analytically more accurate than equilibrium dialysis methods. PMID- 2247774 TI - Compartmental analysis of short-lived platelet dynamics. AB - 111In-labelled platelets were used for analysing platelet dynamics in 43 patients with idiopathic thrombocytopenic purpura (ITP). The detected time-activity curves, recorded with a gamma camera, were analysed by three methods: two- and three-compartment models, and an open model in which only the splenic curve was analysed. In the two-compartment model the mean rate constant from blood to spleen was 0.328 +/- 0.028 min-1 (mean +/- SEM) and from spleen to blood 0.061 +/ 0.007 min-1, whereas in the three-compartment model the corresponding values were 0.236 +/- 0.020 and 0.044 +/- 0.007 min-1, respectively. The mean rate constant from blood to liver was 0.466 +/- 0.149 min-1 and from liver to blood 0.341 +/- 0.106 min-1 as derived from the three-compartment model. The rate constant from spleen to blood, as determined from the three-compartment model, was significantly higher in patients with a strongly positive result for platelet associated auto-antibodies (platelet suspension immunofluorescence test (PSIFT] than in patients with a negative PSIFT. The mean hepatic net rate in patients with a high level of antibodies is into the liver, while in patients with little or no antibodies the net rate is into the blood pool. The mean half-life for the fast component of the inverted splenic curve was 2.5 +/- 0.2 min and for the slow component 16 +/- 2 min. In patients with a strongly positive PSIFT the half-life for the slow component was significantly longer than in patients with a negative PSIFT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247775 TI - Adsorption of creatinine to Fuller's earth. AB - In search for a secondary reference method for the determination of creatinine, the adsorption of creatinine to seven different commercial batches of Fuller's earth have been investigated. Mineralogical investigation of the batches broadly divided them into two subgroups with quite different cation exchange capacities (CEC): dominant smectitic with and without calcium carbonate and dominant palygorskitic with calcium carbonate. Adsorption experiments using 14C-creatinine show, for all Fuller's earth samples, an incomplete adsorption of creatinine. The amount of creatinine adsorbed depends on pH, temperature, concentration of cations as Ca2+ and Na+, and other conditions. Weakly acidic suspensions of Fuller's earth in the course of time change their ability to adsorb creatinine. Compared to a synthetic strong acidic cation exchanger, Fuller's earth is more selective to creatinine. Because of the sensitivity of the adsorption to the various experimental conditions a determination of creatinine in biological fluids using Fuller's earth is too variable. Therefore, we cannot recommend this procedure as a secondary reference method for the determination of creatinine. PMID- 2247776 TI - Stanozolol and experimental atherosclerosis: atherosclerotic development and blood lipids during anabolic steroid therapy of New Zealand white rabbits. AB - Exogenous oestrogens have been shown to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and reduce the severity of experimental atherosclerosis. In contrast, exogenous progestogens, testosterone and anabolic steroids have been shown to increase the level of LDL cholesterol and decrease the level of HDL cholesterol in man. We induced atheromatosis through cholesterol feeding of New Zealand White rabbits of 1% cholesterol (w/w) food supplementation for three months. Furthermore, control rabbits and cholesterol rabbits respectively, were given stanozolol 5 mg per day orally for the first 6 weeks and thereafter 10 mg per day. We found no significant influence of the anabolic steroid stanozolol either on the extent of atherosclerotic involvement or on HDL or LDL cholesterol. However, we could not exclude an influence of stanozolol on the development of atherosclerosis because of the finding that two out of 10 stanozolol-treated rabbits on normal diet developed macroscopic atherosclerosis compared to none out of 72 rabbits of the same age from previous studies given the same normal diet (p = 0.013). PMID- 2247777 TI - [Fractures due to primary tumors and tumor-like changes]. AB - The incidence of pathological fractures resulting from primary bone tumors and tumor-like lesions and various treatment options for such fractures are discussed. In addition to the benign/malignant nature, site, and extent of the tumorous lesion, the patient's age and activity level have to be considered if optimal treatment is to be selected. The treatment is completely different for a pathological fracture resulting from a benign tumor or a tumor-like lesion than for a fracture resulting from a primary malignant bone tumor. As a rule, benign tumors and tumor-like lesions require wide curettage when a fracture occurs, until macroscopically normal bone is reached. The residual cavity is then filled with autogenous cancellous bone grafts. Other fractures, e.g. those resulting from solitary bone cysts, may be treated as if normal bone were concerned. On the other hand, the treatment of a pathological fracture resulting from a primary malignant bone tumor is subordinate to the management of the primary disease, which may be life-threatening. A pathological fracture means a poorer prognosis because of contamination of the surrounding tissues. The risk of local recurrence is high, so that in most cases wide or radical resection or amputation is required. PMID- 2247778 TI - [Surgical measures in metastatic lesions of the extremities and pelvic bones]. AB - Two factors--generally increased life expectancy with a higher risk of malignant disease and improved survival rates among cancer patients--have led to a steady increase in the incidence of metastatic bone disease over the past 20 years. There is little controversy about the need for ORIF in the case of pathological fractures, but special techniques are necessary to achieve immediate and lasting stability in the presence of frequently extensive bone destruction. Metastatic bone lesions that involve the risk of fracture should preferably be stabilized prophylactically before further treatment in the form of radiation or chemotherapy. Special techniques of composite osteosyntheses for the long bones and particularly for composite reconstructions of acetabular lesions are listed. PMID- 2247779 TI - [Spinal metastases and metastasis-induced pathological fractures of the spine]. AB - The vertebral column is a common site of metastatic disease to the bone. The incidence is very high and varies with tumor type. Radiation therapy is effective in the treatment of most cases of spinal metastases. Pathologic fractures of the vertebral body occur in 30-50% of the patients affected, indicating an operative intervention. The ultimate aim of the operation is to increase the patients' quality of life. The tumor mass is normally located in the vertebral body. Therefore, only with an anterior approach can excellent decompression of the spinal cord and reduction of the tumorous tissue be achieved. In patients with advanced metastatic disease, however, in whom an anterior approach is not practicable, tumor decompression may be accomplished through a costotransversectomy combined with posterior stabilization of the spine. Laminectomy is rarely indicated, and then for posteriorly located tumor tissue, and should be combined with dorsal stabilization of the spine. With reference to a few actual cases, we present the approaches and stabilization methods currently in use at our clinic. PMID- 2247781 TI - [Multiple recurrence of tibial fracture]. AB - After a historical review of the term refracture and the related nomenclature, three cases of multiple refracture of the tibia are presented. Radiological findings confirm that the major etiology in refracture is bone necrosis as a result of vascular damage caused by the initial trauma and/or the surgical maneuvers performed to treat it. Normal loads then lead to microfractures of the avascular bone, which is unable to provide adequate substitution or remodelling. In our three cases not only was the periosteal blood supply diminished, but also the medullary canal was narrowed or closed at the fracture site by bone fragments and/or poorly vascularized new bone formation. These pathogenetic findings are supported by experimental studies. Part of the logical therapeutic concept is the opening of the medullary canal and closed medullary nailing. Although reaming and intramedullary rod placement causes transient circulatory disturbances in the inner diaphyseal cortex, this allows restoration of the medullary vascular network. Bone perfusion of the refracture zone is thereby improved and definitive consolidation can take place, as shown in our three cases. PMID- 2247780 TI - [Femoral fractures following total hip prosthesis]. AB - Fractures of the ipsilateral femur after hip arthroplasty are a serious problem. In most cases, minimal trauma is responsible for the fracture. Predisposing factors, such as severe osteoporosis, loosening of the stem of the prosthesis, or cortex perforations, are often found. Such fractures occurred between 1979 and 1989 in 30 patients, i.e. 2.3% of our patients who had received primary prosthesis and 2.9% of those who had undergone revision. The patients' ages at the time of fracture ranged from 41 to 88 years (mean 63 years), 33% of the patients in these group being female. The time lapse from implantation of the prosthesis to the fracture varied between 1 month and 11 years (mean 4.4 years). The fracture was at the level of the proximal trochanteric region in 3% of these patients, between the trochanteric line and the tip of the prosthesis in 20%, and below the tip of the prosthesis in 70%. Operative treatment was performed in 29 patients. Fractures were fixed with a compression plate in 19 (63%), and in 3 the plate fixation was reinforced with intramedullary cement. In 2 osteoporotic patients with supracondylar fractures the osteosynthesis ruptured and a successful revision operation with cement was performed. In 3 others internal fixation was combined with replacement of the prosthesis; 3 patients received a Wagner revision prosthesis and 1 a long-stem Protek tumor prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247782 TI - [Osteosynthesis in high-grade osteoporosis]. AB - Operative treatment of fractures in osteoporotic bone using standard techniques such as are applied in normal bone leads to special problems. The major difficulty is the limited anchorage of any implant in osteoporotic bone. To improve the stability of an implant in osteoporotic bone the following techniques are applicable, either singly or in combination: impaction, long-distance splinting, large-area surface buttressing, osteotomy, and the use of bone cement as a spacer and to improve the purchase of screws. The different techniques are discussed and examples of their application are presented. PMID- 2247783 TI - [Determination of levels of ethyl alcohol in saliva as an important biological material]. AB - Saliva can be suitable biological material for assessment of the ethanol level, in particular in those subjects who for various reasons refuse to have blood samples taken. This statement is based on the results of a trail in 123 subjects. Probands were given alcoholic beverages in amounts that the ethanol level--with regard to the danger of intolerance--if possible did not exceed 1.5 g.kg-1 in the blood stream. Approximately 90 mins. after ingestion of the alcoholic beverage, i.e. during the postabsorptive stage blood and saliva specimens were collected assessment of the ethanol level. Comparison of ethanol levels in blood and saliva revealed in 78 subjects identical levels. In 40 subjects there was a difference of +/- 0.1 g.kg-1 and only in five subjects ther was a difference of +/- 0.2 g.kg 1. These differences can be considered negligible with regard to hitherto used estimates of the ethanol level in other biological materials. From the experiment it is also apparent that the ethanol level does not change substantially when saliva is stored for periods up to 6 days when the final examination be mode. PMID- 2247784 TI - [Determination of pregnancy by detection of SP1 in tissues]. AB - During investigations of murder sometimes in addition to traces of blood only some organs, tissues and remnants of the victim's body are available. Evidence of pregnancy in the residues, mere portions of the divided body without the genitalia would provide important information for the investigation and would help to classify the parts of the body and to identify the victim. Using double radial immunodiffusion in the modification of permanent elution by means of anti SP 1 antiserum produced according to Malbohan and antiserum of Dakopatts Co. (Glostrum, Denmark) in tissue excisions and tissue impressions the pregnancy product SP 1 (pregnancy-specific-beta-1-glycoprotein) was detected. The author examined 269 different specimens: 1. excisions of organs from women who died during the 8th-35th week of pregnancy by sudden and violent death (43 specimens). 2. excisions which were made during surgical operations of pregnant women during the 8th-20th week of pregnancy (16 specimens) and during delivery by Caesarean section (210 specimens). Excisions from the kidneys, spleen, lungs, liver, heart, skeletal muscle, subcutaneous layer, skin, brain were examined from corpses. During operations excisions from the subcutaneous layer, uterus, skin, great omentum, peritoneum, and oviduct were made and examined. Furthermore the author made 3. impressions of tissues on washed cotton material. In the organs collected on necropsy from pregnant women SP 1 was detected in 82% of the specimens, with the exception of the brain where it was never detected. In tissues from operated pregnant women during the first half of pregnancy SP 1 was detected in 63% specimens incl. only in 33% in the 8th week of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247785 TI - Occupational health of farmworkers. PMID- 2247786 TI - The challenge of malignant mesothelioma. PMID- 2247787 TI - The potential of local authority health services in the provision of comprehensive primary health care in the RSA. PMID- 2247788 TI - Choice of coronary heart disease risk factor variables in a cross-sectional study of white South Africans. AB - This report explores the possibility of redefining risk factors so as to improve their observed associations with prevalent coronary heart disease (CHD). A large cross-sectional community study of 5,895 white males and females aged 25-64 years yielded 240 cases of confirmed angina pectoris and 361 of confirmed myocardial infarction. Odds ratios for CHD end-points by level of risk factors when risk factors were expressed in the conventional manner (e.g. total cholesterol, systolic and diastolic blood pressure or current smoking) were often low and not statistically significant. Redefinition of risk factor variables in a manner that improved their specificity or compensated to some extent for the decreased risk factor exposure as a result of a CHD event (e.g. stopping smoking after a myocardial infarct) improved the strength of association. In this study, the most useful cholesterol variable was total cholesterol minus high-density lipoprotein cholesterol; for blood pressure the most useful variable was a blood pressure of 160/95 mmHg or above and/or being on anti-hypertensive treatment; and for smoking the most useful variable was the total duration of smoking (previous and current). Strong associations with CHD end-points were also found for conventionally expressed serum uric acid, diabetes prevalence (females) and family history of CHD. The study suggests that appropriate redefinition of risk factor variables and CHD end-points in cross-sectional studies yields associations similar in strength and direction to those found in prospective studies. PMID- 2247789 TI - Automation of serum cholinesterase assay--paediatric and adult reference ranges. AB - Serum cholinesterase (CHE) activity falls dramatically with organophosphate poisoning. In view of the need for an accurate, reproducible and inexpensive method for screening large numbers of farmworkers and others exposed to organophosphates, a manual commercial method was modified for use on an automated (centrifugal) chemistry analyser. The resultant procedure can be performed rapidly with a 24-fold cost-saving over the manual method. The volume of sample required is small, results of the automated and manual method showed excellent correlation and the reproducibility characteristics of the automated assay procedure was adequate for clinical use. Reference ranges were determined on children and adults. The results best fitted two reference ranges: children and adult females had a combined mean of 5,687 U/I with a lower (2,5 percentile) and upper (97,5 percentile) limit of 3,070 U/I and 8,483 U/I, respectively. The corresponding figures for adult men were 8,607 U/I (mean), 4,687 U/I and 9,116 U/I. The results also strongly suggested that pregnant women and women taking oral contraceptives had CHE activities approximately 12% lower than the female reference range quoted above. The numbers evaluated were too small, however, to construct a separate reference range for this category. PMID- 2247790 TI - Low serum cholinesterase levels in rural workers exposed to organophosphate pesticide sprays. AB - An automated assay for plasma cholinesterase (CHE) activity (EC 3.1.1.8) was used to screen 44 farmworkers engaged in fruit crop spraying in the Somerset West, CP, area. Seven had markedly reduced CHE activity, at least 30% below the lower limit of the urban reference range, while the group as a whole had moderately depressed levels. A screen of 14 nursery-workers from the same farm showed a similar picture with the 1 individual engaged in spraying duties having an extremely low CHE activity of 1,595 U/I (lower normal limit for adult males is 4,687 U/I). Clinical complaints were few and were described as 'asthma' and 'chronic bronchitis' by the nursing sister in charge of the staff clinic. The mean body mass of the 7 farmworkers with substantially reduced CHE activities was 7,4 kg lower than the others and this was accompanied by significantly diminished body mass index. Removal of the 7 worst affected individuals from spraying duties for a period of 6 weeks resulted in a statistically significant increase in CHE activity of 1,700 U/I, whereas the values in the remaining workers remained unchanged. These results strongly suggest that at least 17,5% of male rural workers engaged in crop spraying suffer from chronic organosphosphate poisoning. The somewhat depressed levels of CHE activity in the rural group as a whole may also reflect chronic exposure of a lesser degree. All 7 female workers tested had enzyme activities within the normal range. PMID- 2247792 TI - The relevance of a First-World therapeutic drug monitoring service to the treatment of epilepsy in Third-World conditions. AB - In May 1988 a Therapeutic Drug Monitoring (TDM) service for anti-epileptic drugs was established at Prince Mshiyeni Memorial Hospital. This service was offered as a multidisciplinary team approach involving sisters, doctors, social workers and pharmacists at an epilepsy clinic. Statistics gathered over a 13-month period showed that: (i) epileptic patient numbers increased from 52 to 211 per 4-week cycle, while patients requiring TDM decreased from 40 to 20 per cycle; (ii) phenytoin was the most frequently prescribed anticonvulsant, followed by carbamazepine and phenobarbitone, throughout the period; (iii) TDM did not alter prescribing patterns--approximately 90% of patients were on monotherapy at the beginning and at the end of the assessment period; (iv) 471 serum levels were measured in 280 patients over 13 months. Phenytoin serum levels constituted the majority (53%) followed by carbamazepine (33%), phenobarbitone (12%) and valproate (2%); (v) of the levels measured in 24 patients taking phenytoin 300 mg/d who were experiencing neither seizures nor side-effects, 38% of levels were in the potentially toxic range; and (vi) well-controlled patients increased from 36% in the first cycle to 60% in the last cycle. A TDM service is very useful in a Third-World setting and can assist in conserving scarce sources provided it is utilised within a holistic treatment framework. PMID- 2247791 TI - Mortality of an asbestos-exposed birth cohort. A pilot study. AB - A pilot study on the health effects of environmental exposure to asbestos (in particular the development of mesothelioma) is almost complete. This is a record linkage study, using birth and death records as the primary sources of data. The vital status and, if applicable, the cause of death was examined for each of the 1227 members of the 'pilot' cohort (birth years 1932-1936). Preliminary results are presented. Eighty-seven per cent (399) of the white cohort members have been traced and the vital status of each has been determined. Sixty-six whites have died, 6 from mesothelioma. It is almost impossible to trace the black and coloured cohort members and the main study, covering the years of birth 1917 1936, may have to be restricted to whites. PMID- 2247793 TI - Medical manpower--South African situation models for planning and recommendations. AB - Imbalances in medical manpower in South Africa are outlined. Theoretical publications on health manpower development are reviewed, with particular reference to factors and problems to be considered when estimating health manpower needs. Four models (health demand, health needs, service target and manpower/population ratio) of health manpower planning are described and their applicability to the South African situation is discussed. Recommendations for health manpower development in South Africa, especially for primary health care, are made. PMID- 2247794 TI - Aspects of work of women medical doctors in the Cape Province. A preliminary investigation. AB - Women form an increasingly important part of the medically trained workforce in South Africa. However, little is known about the professional issues and work related problems affecting them. A survey was undertaken of all registered female medical practitioners practising in the Cape Province in order: (i) to ascertain their current pattern of work; (ii) to identify factors that influence this work pattern; and (iii) to identify factors that would help these women stay in the profession or re-enter it more easily after an absence. A questionnaire on biographical information, qualifications, employment (full-time/part-time), capacity in which employed, ease of keeping up to date, information about those participants not at present practising medicine, and changes in working conditions that would make it easier for those not practising to return to medical practice was posted to all eligible doctors. Of 774 copies posted, 480 were returned (62%). At the time of the survey, 90% of the respondents under 65 years of age were employed. The reason most often cited as to why respondents stopped practising was family commitments. The availability of part-time posts was most often mentioned as a working condition that would make return to work easier. Twice as many respondents found it difficult or very difficult to keep up with current practices than those who found it easy or very easy. There were 196 women (41%) who had been unemployed for more than 6 months; 44 ascribed this to the unavailability of posts. Women doctors need more flexible training schedules and conditions of employment. Part-time training and part-time career options should be extended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2247795 TI - Low-dose intrathecal morphine sulphate as sole analgesic for pain of labour in combination with elective forceps delivery. A report of 10 cases. AB - Preservative-free morphine sulphate (0.5 mg in 0.5 ml normal saline) was injected intrathecally as the sole analgesic in 10 primiparous patients in the first stage of labour. Elective forceps were applied under pudendal block anaesthesia to assist the second stage of labour to prevent cephalad spread during bearing down, and so reduce the side-effects of morphine sulphate. All patients reported good analgesia during the first stage of labour. There was no loss of the bearing down reflex and, except for mild peri-oral itching in 6 patients, no side-effect attributable to intrathecal morphine was noted. No side-effects of morphine sulphate were observed in any of the infants delivered. It is concluded that intrathecal morphine sulphate combined with elective forceps delivery provides a satisfactory alternative to epidural anaesthesia in those patients whose cardiovascular status demands preservation of a normal or elevated systemic vascular resistance. PMID- 2247796 TI - Extracorporeal surgery for renal tumour. A case report. AB - A case of adenocarcinoma of a single functioning kidney is presented. The tumour was removed by extracorporeal bench surgery and the remnant successfully autotransplanted. PMID- 2247797 TI - Posterior tibial nerve neurotmesis complicating a closed tibial fracture. A case report. AB - A case of complete transection of the posterior tibial nerve complicating a closed mid-shaft fracture of the tibia is reported. Early surgical exploration and repair resulted in return of function within 6 months. Such injuries are not common, but the case described highlights the importance of vigilance in assessment of all limb fractures. PMID- 2247798 TI - Benign intracranial hypertension in typhoid fever. A case report. AB - Benign intracranial hypertension, a previously undocumented neurological complication of typhoid fever, is described in an 11-year-old child. Resolution occurred within 5 days of the start of chloramphenicol therapy and recovery was uneventful. PMID- 2247799 TI - A closer look at the oxyhemoglobin-dissociation curve. PMID- 2247800 TI - Sexually transmitted diseases and tubal pregnancy. AB - The risk of tubal pregnancy associated with seropositivity to Chlamydia trachomatis or following a diagnosis of gonorrhea, genital herpes, trichomoniasis, genital warts, or nonspecific vaginal infection was evaluated in a study of this condition among women who were members of a prepaid health plan. A total of 264 women who had a tubal pregnancy between 1981 and 1986 were interviewed about their history of these sexually transmitted diseases (STDs). Their responses were compared to those of 715 women who were matched by age and county of residence but were otherwise randomly selected from the enrollment files of the health plan. Chlamydia antibody status was known in a sample of 135 cases and 192 controls. Although more cases reported a history of gonorrhea, trichomoniasis, and non-specific vaginal infections than did controls, only a modestly elevated risk for trichomoniasis remained after logistic regression was used to adjust for the effects of age, reference year, race, presence of contraception at reference date, seropositivity to Chlamydia trachomatis, and a history of other STDs. By contrast, among women for whom Chlamydia trachomatis antibody status was assessed, presence of antibody was associated with a two-fold increase in the risk of tubal pregnancy after adjusting for the effects of the previously enumerated variables. These findings confirm the relevance of Chlamydia trachomatis as a risk factor for ectopic pregnancy, and they also underscore the importance of adjustment for the influence of other STDs when evaluating the association between a specific STD and the occurrence of tubal pregnancy. PMID- 2247801 TI - Human immunodeficiency virus infection in women attending an inner-city prenatal clinic: ineffectiveness of targeted screening. AB - Women attending an inner-city prenatal clinic between February, 1987 and August, 1988 completed a questionnaire to assess risk factors for human immunodeficiency virus (HIV) infection. Women with risk factors were offered HIV testing. Testing was available to women without risk factors upon their request. Stored sera were obtained for anonymous HIV testing on patients not consenting for testing. Overall, 30 of 622 women (5%) tested HIV positive. Ten per cent of women acknowledging risk factors were seropositive vs 3% denying risk factors (P less than .001). Intravenous (IV) drug use was reported in 40% of seropositive women. However, 47% (14/30) of HIV seropositive women denied risk factors for infection. Limiting prenatal HIV screening to women acknowledging risk factors may fail to identify a substantial number of infected women. Screening for HIV infection, counseling, and education on risk reduction should be offered to all pregnant women. PMID- 2247802 TI - A comparative study of topical analgesia with a lidocaine/prilocaine cream (EMLA) and infiltration anesthesia for laser surgery of genital warts in men. AB - Treatment of genital warts by laser surgery was performed in 100 male patients under local infiltration (2-6 ml 1% Xylocaine) or topical anesthesia with 2.5-7.5 ml EMLA cream. EMLA cream was applied to the warts ten minutes before the operation. Pain was significantly less during application of EMLA than during infiltration of Xylocaine. Infiltration anesthesia resulted in better surgical analgesia than EMLA, although the difference was small. The combined pain scores of application and surgery were significantly smaller in the EMLA group. The result suggests that EMLA applied for ten minutes constitutes a less painful treatment and is thus the anesthetic of choice for the laser surgery of genital warts. PMID- 2247803 TI - Reproductive health practices in women attending an inner-city STD clinic. AB - Inner-city sexually transmitted disease (STD) clinics may provide an important access point to educate patients at high risk for reproductive health problems and their peers in order to effect behavior change. In a pilot study to evaluate the knowledge, health practices, and behavior of patients attending an inner-city STD clinic, 116 women were surveyed concerning their reproductive and general health practices, their knowledge of both, and screened for STDs. The women who had a history of first intercourse before age 18 years had a statistically significant higher rate of infection. Thirty-three percent of the patients did not know the purpose of a Pap smear; of the 67% who stated that they did know, only 30% actually stated that a Pap smear is used to detect cancer. STD clinics offer a unique opportunity for the integration of health care services and education to a group of high-risk patients. PMID- 2247805 TI - Evaluation of Abbott Testpack Chlamydia for detection of Chlamydia trachomatis in patients attending sexually transmitted diseases clinics. AB - This work compares a rapid solid-phase EIA (Abbott TestPack Chlamydia) to tissue culture and a direct fluorescent antibody test (Syva Microtrak) for detection of C. trachomatis in 436 patients attending two inner-city sexually transmitted diseases (STD) clinics. The prevalence of C. trachomatis by culture was 12% (5% in men, 15% in women). Overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TestPack compared to culture were 70%, 98%, 80%, and 96% respectively. In men, 12 specimens were positive by TestPack, while only eight specimens were positive by culture. Six TestPack positive, culture-negative specimens were further evaluated by centrifugation of culture transport media and examination of the sediment for chlamydia elementary bodies (EBs) using fluorescent monoclonal antibodies to C. trachomatis. Using this procedure, five of six culture negative specimens contained EBs (revised sensitivity 85%, specificity 99%, PPV 92%, NPV 99%). In 285 women evaluable in culture and TestPack, 44 (15%) specimens were culture positive; TestPack was positive in 29 (sensitivity 66%) culture positive women. Of 241 culture negative patients, 238 had negative TestPack results (specificity 99%) and no EBs were detected in the culture-negative, TestPack-positive specimens. Twenty-three (8%) Microtrak specimens were unsatisfactory for testing; two of these were culture and TestPack positive. Therefore, of 263 specimens evaluable using Microtrak, 42 (16%) specimens were culture positive; Microtrak was positive in 32 (sensitivity 76%) culture-positive women. Abbott TestPack Chlamydia is a rapid (25 minute), visually read format requiring no specialized equipment for detection of chalmydia infections with a sensitivity comparable to that of Microtrak. PMID- 2247804 TI - Chlamydia trachomatis infection in women attending urban midwestern family planning and community health clinics: risk factors, selective screening, and evaluation of non-culture techniques. AB - To determine prevalence and risk factors for endocervical Chlamydia trachomatis infection in an urban midwestern population and to evaluate two non-culture direct tests for C. trachomatis, we studied 849 women attending two family planning clinics and a community health clinic in Milwaukee, Wisconsin. Adequate endocervical specimens were obtained from 751 women for chlamydial isolation in tissue culture and antigen tests using direct fluorescence (DFA) and enzyme immunoassay (EIA); 93 (12.4%) patients had cultures positive for C. trachomatis. Compared to culture, the DFA test had a 77.4% sensitivity, 96.8% specificity, and a predictive value positive (PVP) of 77%. For the EIA, these values were 83.9%, 97.0%, and 80%, respectively. No single historical, clinical, or laboratory variable, including the previously described cervicitis index and specific cytologic findings on Pap smear, had sufficient predictive value to be used as the only criterion for selective screening in this population. Criteria for selective screening were proposed that would result in screening 43% of patients and would identify 71% of infections. PVP of both non-culture tests was 89% in persons identified by these criteria to be at increased risk of C. trachomatis infection. PMID- 2247806 TI - Subcutaneous interferon alpha in the treatment of refractory condylomata. AB - Fifteen patients (mean age 24, range 19-46) referred for refractory vulvar warts were treated with subcutaneous interferon alpha-2a, 3 million units 3 times a week for 3 weeks. The cumulative rate of complete response was 14% at 2 weeks, 27% at one month, and 36% at three months. The response was independent of the duration of warts. The mean number of vulvar warts was 7 (range 3 to 9) among patients with complete response, 11 (range 4-20) among patients with partial response, and 23 (range 4-35) among patients with no response. The presence of cytologic or colposcopic abnormality of the cervix also predicted poor response. Adverse effects were usually mild. One patient developed progression of warts at one month and was dropped from the study. Future studies should explore the use of interferon as an adjuvant to other treatment modalities. PMID- 2247807 TI - Expanded NIAID support of STD research: STD Cooperative Research Centers. PMID- 2247808 TI - Asymptomatic urethral carriage of Chlamydia trachomatis in male patients with genital ulcerations in Paris, France. PMID- 2247809 TI - Use of penicillin for venereal disease in World War II. PMID- 2247810 TI - Pathogenesis of gallstones. AB - The many developments in nonoperative methods for the treatment of gallstone disease underscore the importance of understanding the pathogenesis of these stones. Elucidation of the factors responsible for nucleation of crystals and the mechanism by which it occurs would appear to be the challenge if we are to define the cascade of events that results in gallstone formation. PMID- 2247811 TI - Biliary tract surgery. PMID- 2247812 TI - Gallstone dissolution. AB - Many methods are available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin or methyl tert-butyl either; and calcium or pigment solvents such as EDTA and polysorbate. Which of these approaches will be appropriate for an individual patient depends on the type of stones; whether they are in the gallbladder or the bile ducts; whether access to the biliary tree is available; the patient's age and general medical condition; and the availability of necessary expertise. In the US, both chenodeoxycholate and ursodeoxycholate are now available. Ursodeoxycholate is more expensive but appears to produce fewer side effects and may be more efficacious. These agents are most effective in thin women with small floating, radiolucent cholesterol stones in a functioning gallbladder. Only about half of the small subset of patients will experience partial or complete dissolution of stones within a year. Stone recurrence and the potential toxicity of long-term therapy are problems with this approach. Therefore, for most patients, cholecystectomy, either in the traditional fashion or using a laparoscopic approach (see article later in this issue by Gadacz et al), is the most cost-effective and perhaps the safest option. Intragallbladder instillation of methyl tert-butyl ether probably will be applicable only to a small subset of patients, and treatment is likely to be followed by a high recurrence rate. In patients with retained common duct cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be initiated as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90% success rate with this technique can be expected within 7 days. PMID- 2247814 TI - Surgery for acute and chronic cholecystitis. AB - Cholecystostomy and cholecystectomy remain appropriate and effective therapy for acute and chronic cholecystitis. Cholecystectomy is the gold standard against which all alternative methods of treatment of inflammatory biliary stone disease should be judged. The pathogenesis, diagnosis, and surgical treatment of acute and chronic cholecystitis have been described. Techniques of cholecystostomy, cholecystectomy, and intraoperative cholangiography used by the author have been given. Our results and those generally described in the literature indicate that the overall mortality rate for cholecystectomy, in all age groups, is approximately 0.5%. This rate increases slightly in patients with acute cholecystitis and in those over the age of 65 years. Cholecystectomy remains the most effective and the definitive treatment for acute and chronic cholecystitis. PMID- 2247813 TI - Extracorporeal shock wave lithotripsy for biliary stones. AB - Extracorporeal shock wave lithotripsy is a noninvasive technique for treatment of patients with gallbladder and bile duct stones. Selected patients with gallbladder stones can be treated on an outpatient basis without general anesthesia and may return to full activity within 1 or 2 days. Stone-free rates of 40% to 60% at 6 months have been achieved in most reported series with minimal morbidity. Bile duct stone lithotripsy has achieved stone clearance in 80% of patients in whom conventional methods were unsuccessful and therefore constitutes a valuable second-line treatment for these patients. PMID- 2247815 TI - Gallstone pancreatitis. AB - Gallstone pancreatitis is caused by transient obstruction of the ampulla of Vater by a migrating gallstone. Intraglandular activation of pancreatic enzymes occurs (by an unclear mechanism), and their entry into the circulation causes most of the local and systemic events of pancreatitis. The diagnosis is based on history and physical examination, an elevation of serum amylase above 1000 IU/L, and ultrasound and CT scans. Endoscopic retrograde cholangiopancreatography can be used in less certain cases to confirm the presence of common bile duct stones. Because of the absence of an agent that can abort progression of the disease, therapy should consist of adequate resuscitation, nutritional support, and careful monitoring to detect early complications. In patients with mild pancreatitis, surgery usually can be performed within 48 or 72 hours of admission or as soon as symptoms and amylase levels return to normal. For patients with severe disease, endoscopic sphincterotomy is emerging as the therapeutic modality of choice. Elective treatment of the associated biliary disease should be performed during the same hospitalization after the acute phase of the disease has subsided. PMID- 2247816 TI - Acute cholangitis. AB - Cholangitis is an infection of the biliary ductal system that results from the combination of bactibilia and biliary obstruction. Choledocholithiasis has been the leading cause of cholangitis. However, in recent years, especially at tertiary referral centers, nonoperative biliary manipulations, often in patients with unresectable malignancies, have become the most common cause of cholangitis. As a result, the complete triad of fever and chills, jaundice, and abdominal pain, as originally described by Charcot, is now seen less frequently. Most patients still have leukocytosis and abnormal liver function tests, but many patients with indwelling tubes may develop cholangitis without significant jaundice. E. coli, Klebsiella species, and the enterococci remain the most frequently isolated organisms, and anaerobes including Bacteroides fragilis are recovered in 15% to 30% of patients. However, Enterobacter and Pseudomonas species, as well as yeasts, are now being isolated more frequently from patients with indwelling tubes, who often have been treated previously with antibiotics. Computed cholangiography usually is necessary to determine the cause and site of biliary obstruction. In the majority of patients with cholangitis, cholangiography can be delayed until the patient has been afebrile for a minimum of 24 to 48 hours. Initial therapy includes bowel rest, intravenous fluids, and antibiotics. Many antibiotic regimens are now available to cover the gram negative aerobes, the enterococcus, and the anaerobes that are likely to be causing the biliary infection. The combination of a penicillin and an aminoglycoside has been the gold standard. However, recent studies suggest that the newer broad-spectrum penicillins provide adequate therapy for these patients. Only a small percentage (5%-10%) of patients with toxic cholangitis require emergency biliary decompression. The choice of percutaneous or endoscopic drainage should be made on the basis of the presumed site and cause of obstruction as well as local expertise. The nature of the biliary obstruction may be the most important determinant of outcome. At present, patients with end-stage malignant obstruction account for most of the deaths, whereas approximately 95% of patients survive an episode of cholangitis. PMID- 2247817 TI - Nonoperative management of bile duct stones. AB - The treatment of choice for most retained bile duct stones is by nonoperative means. If a T-tube is in place, percutaneous techniques via the T-tract are indicated. Percutaneous access via puncture of a Roux-en-Y loop is also practical. In the absence of a T-tube, retrograde endoscopic techniques should be used. Both techniques are very effective and safe. Stones in the intrahepatic and extrahepatic ducts also can be treated nonoperatively. Endoscopic sphincterotomy has a role in the treatment of selected patients with gallstone pancreatitis, acute cholangitis, and choledocholithiasis with in situ gallbladders. In difficult cases, endoscopic and percutaneous techniques are employed in combination. PMID- 2247818 TI - Surgical management of bile duct stones. AB - The biliary surgeon in the 1990s must be familiar with all of the available techniques for the treatment of bile duct stones. Experience and judgment are important in the successful management of the individual patient with intrahepatic or extrahepatic stones. Knowledge of the nonsurgical methods of stone removal is important in the decision-making process. However, the biliary surgeon must resist the temptation to do less than a thorough removal of all stones at the operation lest the patient be subjected to additional procedures, which carry their own risks of morbidity and death. The goal should be to clear the stones from the biliary system with the fewest procedures offering the lowest morbidity and mortality risks to the patient. PMID- 2247819 TI - Stenosis of the sphincter of Oddi. AB - "Stenosing papillitis" is a descriptive term for an anatomic deformity of the papilla of Vater that is characterized by narrowing of the lower end of the bile duct and the proximal end of the duct of Wirsung. The defect is secondary to inflammation and fibrosis from the chronic passage of gallstones, episodes of acute pancreatitis, chronic pancreatitis, sclerosing cholangitis, peptic ulcer disease, and cholesterolosis. Patients with papillary stenosis from gallstones may present with episodes of severe upper-abdominal pain several years after cholecystectomy. The pain is often incapacitating, and patients are often addicted to narcotic analgesics. The work-up includes abdominal ultrasonography and CT scanning and endoscopic retrograde cholangiopancreatography even though the findings usually are normal. Liver and pancreatic enzymes are not frequently elevated with the painful episodes. Transendoscopic manometry may reveal elevated pressures within the papillary portion of the distal bile duct. Some patients are relieved of their pain by transduodenal sphincteroplasty and transampullary septectomy, thereby ablating the sphincter of Oddi around the bile and pancreatic ducts and enlarging their openings. PMID- 2247820 TI - Postoperative bile duct strictures. AB - Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs. PMID- 2247821 TI - Primary sclerosing cholangitis. AB - Primary sclerosing cholangitis is a rare disease of unknown etiology. Sclerosis of the bile ducts may actually be the final result of multiple factors such as autoimmune, bacterial, congenital, drug, or viral injury. The most commonly associated diseases are ulcerative colitis and chronic pancreatitis. Except in the earliest stages of the disease, liver histologic findings are not specific. Most patients present with jaundice, pain, and pruritus, although an increasing number of asymptomatic patients with inflammatory bowel disease and abnormal liver function are being identified. Cholangiography is key to the diagnosis and is usually pathognomonic except in the unusual case where primary sclerosing cholangitis is confused with cholangiocarcinoma. Many forms of medical therapy have been tried, including antibiotics, azathioprine, cholestyramine, colchicine, cyclosporine, D-penicillamine, steroids, and ursodeoxycholic acid. To date, none of these medications has been proved to alter the course of this disease. Recent reports of ursodeoxycholic acid trials have been encouraging, but long-term results of ongoing randomized trials have yet to be published. In recent years, balloon dilatation of biliary strictures has been accomplished via endoscopic and percutaneous transhepatic approaches. However, in patients with primary sclerosing cholangitis, these nonoperative manipulations must be done repeatedly, may entail multiple general anesthetics, and are difficult to perform. We believe that a direct surgical approach to the biliary tree with long-term transhepatic stenting is indicated in selected patients with severe hilar or extrahepatic stricturing, persistent jaundice or recurrent cholangitis, and no evidence of cirrhosis. Hepatic transplantation should be reserved for patients with primary sclerosing cholangitis who have well-established cirrhosis and have not responded to other therapeutic measures. PMID- 2247823 TI - Carcinoma of the gallbladder. AB - Gallbladder cancer remains difficult to diagnose preoperatively. However, recent work suggests that ultrasound may be effective. Gallbladder cancer remains highly lethal despite aggressive therapy. Extension of the disease beyond the mucosa predicts a poor chance of long-term survival. PMID- 2247822 TI - Congenital biliary tract disease. AB - Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common channel-type pancreaticobiliary junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Roux-en-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome. PMID- 2247824 TI - Lithiumogenic disorders of the thyroid and parathyroid glands as surgical disease. AB - Little notice has been paid in the surgical literature to problems with psychoeffective lithium, which by interfering with adenylate cyclase affects thyroid and parathyroid function, causing hypercalcemia, hyperparathyroidism, and hypothyroidism. Seven patients with lithiumogenic hyperparathyroidism occurring after years of lithium therapy underwent treatment and manifested osteoporosis (n = 2), hypertension (n = 2), nephrolithiasis (n = 1), coma (n = 1), rising hypercalcemia (n = 1), goitrous myxedema (n = 4), nephrogenic diabetes insipidus (n = 2), renal failure (n = 2), and hyperlipidemia (n = 1). Disease-directed parathyroidectomy (without morbidity) was curative. Unique laboratory findings included normal serum phosphorus and reduced urinary calcium and cyclic adenosine monophosphate values. Three separate cases of thyroid carcinoma after long-term lithium therapy were also treated, being preceded by myxedema (n = 2) and concurrent with hyperparathyroidism (n = 1). There has been only one previous report of lithium-associated thyroid carcinoma. All patients taking lithium should undergo surveillance for thyroid and parathyroid dysfunction and neoplasia, and appropriate surgical and medical treatment should be considered in each situation. Although hyperparathyroidism may be reversible with lithium discontinuance, such therapy may be obligatory for patient well-being, thus dictating parathyroidectomy. PMID- 2247825 TI - Multiple parathyroid adenomas: report of thirty-three cases. AB - An increasing number of patients with primary hyperparathyroidism are found to have two or three enlarged parathyroid glands. Of 865 patients successfully operated on by one surgeon (J.N.A.), multiple enlarged parathyroid glands (adenomas) were found and resected in 33 cases (3.8%), with resulting normocalcemia lasting from 1 to 22 years (mean 5.8). Twenty-nine patients had two adenomas and four had three adenomas. In 28 patients the multiple adenomas were synchronous. Twenty-five patients underwent removal of all of the enlarged parathyroid glands in one operation; in three patients one adenoma was removed, reoperation for persistent hypercalcemia was performed, and a second adenoma was resected with cure. In five patients one adenoma was removed, normocalcemia ensued for 3 to 18 years, and a second (metachronous) adenoma occurred and was resected successfully. Although 10 of 70 enlarged parathyroid glands removed were labeled hyperplasia, cure in all but one of our patients by selective resection of only enlarged parathyroid glands emphasizes the unreliability of histologic criteria in differentiating between parathyroid adenoma and hyperplasia. Based on this study, we support the existence of multiple adenomas and advocate removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism. PMID- 2247826 TI - Endosonography in the localization of parathyroid tumors: a preliminary study. AB - A preoperative transesophageal exploration of the parathyroids by endosonography was performed on 23 patients with primary hyperparathyroidism. The system used was a 7.5 MHz transducer mounted on the tip of an endoscope with an external diameter of 13 mm. The field of visualization was 360 degrees. A retrograde exploration was done moving up from the aortic arch to the upper esophageal sphincter. All patients underwent surgery afterward, and adenomas were found. In 12 cases the adenoma was visualized. All 12 adenomas were posteriorly located on the right side (four cases) and left side (eight cases) of the esophagus. Nine of these 12 tumors were on the posterior face of the thyroid lobes, with six tumors in the middle one third of the thyroid lobe and three in the lower one third of the thyroid lobe. The other three tumors were located below the lower pole of the thyroid lobes in the upper posterior mediastinum. Mean tumor weight was 1165 mg. Of the 11 tumors that could not be visualized, eight tumors were anteriorly located; three of these tumors were on the anterior and lateral surface of the lower pole of the thyroid, and five were in the thyrothymic tracts. The remaining three tumors were located on the back of the thyroid lobes; two of these tumors were at the upper esophageal sphincter, and one was on the side of the pharynx. Mean tumor size was 1334 mg. Localization of parathyroid tumors by endosonography appears possible but only if lesions are located posteriorly, close to the esophagus. Endosonography is not indicated before routine cervical exploration for primary or secondary hyperparathyroidism. As in other such studies, endosonography could be useful in cases of persistent or recurrent hyperparathyroidism. PMID- 2247827 TI - Characterization of a simplified method of cryopreserving human parathyroid tissue. AB - Cryopreservation of human parathyroid tissue plays an important role in managing difficult parathyroid disease. It also can permit investigators to conduct experiments without dependence on the operating room schedule. Availability of cryopreservation has been limited by the perceived need for expensive, complex equipment. We adapted a simple method of freezing cell suspensions to freezing human parathyroid tissue. Vials containing human parathyroid in culture media, dimethylsulfoxide, and patient serum were placed in a plastic rack in a metal pan containing prechilled (4 degrees C) ethanol and placed in a -70 degrees C freezer. We compared viability (trypan blue dye exclusion by collagenase dispersed cells) of tissue frozen in this manner to that of tissue frozen in a programmable liquid nitrogen freezer at 1 degrees C per minute, a cooling rate recommended for human parathyroid tissue. The viability of 30 patients' samples cooled in liquid nitrogen (average length of storage 5 months) was 74% +/- 15% and that of 64 patients' samples cooled in ethanol (average length of storage 26 months) was 71% +/- 15%. Viability of 19 samples of fresh tissue was 79% +/- 10%. Neither method had a statistically significant correlation between length of storage and viability. Successful cryopreservation with simplified technology may expand the availability of parathyroid tissue to meet both clinical and investigative requirements. PMID- 2247828 TI - Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism. AB - Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man. PMID- 2247829 TI - Evaluation of metastatic cardiac calcification in a model of chronic primary hyperparathyroidism. AB - Recent reports have fueled an interest in the prevalence and significance of metastatic calcium deposition in patients with chronic hyperparathyroidism. Experimental data are limited by the lack of suitable in vivo animal models. We have developed a model of marked hypercalcemia and overproduction of parathyroid hormone using somatic gene transfer. Briefly, the process involves infection of cultured rodent fibroblasts (RAT-1 cells) with a retroviral expression vector that contains the gene encoding human parathyroid hormone. Fibroblasts are grown to confluence on collagen-coated dextran microcarrier beads and are injected into the peritoneal cavities of syngeneic Fisher rats. Human parathyroid hormone production in rat serum is quantified by an immunoradiometric assay for human parathyroid hormone (1-84), which does not recognize rat parathyroid hormone. These rats consistently show production of human hormone within a week. Levels increase progressively, often to 1 ng/ml within 60 days of injection. Serum calcium showed a concomitant rise to an average of 15.5 mg/dl. In this study, 13 rats that had been transplanted with parathyroid hormone-producing fibroblasts were killed 80 days after injection. Examination of the skeleton revealed demineralization and histopathologic sequelae of parathyroid hormone excess with extensive osteoclastic bone resorption. Examination of the hearts revealed calcification in five of 13 hearts. There was no involvement of major coronary arteries or conducting systems, but there was calcification of cardiac myocytes, primarily in subepicardial region. This model may permit an understanding of the mechanisms for sudden cardiac death in severe hypercalcemia. PMID- 2247830 TI - Cardiac calcific deposits in patients with primary hyperparathyroidism: preliminary results of a prospective echocardiographic study. AB - To explain the incidence and significance of mitral and aortic valve calcification and calcific deposits in the myocardium, a prospective echocardiographic study was performed with 21 consecutive patients who had primary hyperparathyroidism (PHP) and with 21 age- and sex-matched control subjects with normocalcemia. Calcific deposits in the myocardium were seen in 13 patients (62%) with PHP, mainly in the interventicular septum, and in one control subject. Aortic valve calcification was observed in 12 patients (57%) with PHP and in one control subject. Calcification of the mitral valve was found in seven patients with PHP (33%) and three controls (14%). Calcification led to mild or moderate stenosis of the aortic valve in three patients with PHP and of the mitral valve in two patients with PHP. No stenosis was found in the subjects in the control group. Both calcification of the aortic and mitral valves and calcific deposits in the myocardium are common in patients with PHP and can be detected noninvasively by echocardiography. Because of the potential relationship of elevated calcium, calcification, and valvular heart disease, clinical evaluation of PHP should include echocardiographic studies before surgery is performed and during follow-up examination. PMID- 2247831 TI - Hyperparathyroidism and cellular mechanisms of gastric acid secretion. AB - Patients with hyperparathyroidism appear to be a particular risk for peptic ulcer disease. To test the hypothesis that hypercalcemia or parathyroid hormone plays a role in promoting ulcer disease, we studied the effect of varying concentrations of extracellular calcium on acid secretion using in vitro isolated rabbit gastric glands. Acid secretion was assessed by the accumulation of carbon 14-labeled aminopyrine (14C-AP). Glands were incubated with varying calcium concentrations in the unstimulated state and with histamine or carbachol (10(-7) to 10(-4) mol/L) in 1 or 2 mmol/L calcium medium. The effect of parathyroid hormone was also examined under identical conditions. Compared to 1 mmol/L standard calcium medium, unstimulated 14C-AP accumulation was significantly inhibited (p less than 0.05) at both lower (0.33 mmol/L) and higher (2 and 2.5 mmol/L) calcium concentrations. Accumulation of 14C-AP in response to histamine stimulation was unaffected by alteration of extracellular calcium (p greater than 0.2). Carbachol stimulated 14C-AP accumulation was significantly augmented (p less than 0.01) by an increase in calcium concentration from 1 to 2 mmol/L. The addition of parathyroid hormone (10(-7) to 10(-4) mmol/L) alone or in combination with carbachol or histamine (10(-6) mmol/L) incubation did not alter 14C-AP accumulation. These data suggest that elevations in extracellular calcium play an active role in the potentiation of cholinergic-mediated gastric gland acid secretion and may thereby play a role in hyperparathyroid-related ulcer disease. PMID- 2247832 TI - Management of Cushing's syndrome secondary to adrenal adenoma during pregnancy. AB - This report discusses our experience with two patients who had unilateral adrenalectomy during pregnancy as treatment for Cushing's syndrome secondary to an adrenal adenoma. Previously only five patients with this clinical problem who underwent unilateral adrenalectomy during pregnancy had been reported. We have reviewed the world literature on Cushing's syndrome in pregnancy secondary to an adrenal adenoma. A total of 19 patients who had unilateral adrenalectomy for this problem after the completion of pregnancy were identified. The review of world literature and the two patients who are the subject of this report were the basis of our analysis of fetal death, neonatal complications, and maternal complications in seven pregnancies during which unilateral adrenalectomy was performed (group 1) compared to the 19 pregnancies that were associated with unilateral adrenalectomy at the completion of pregnancy (group 2). Of the seven pregnancies in group 1, one fetal death and no neonatal complications occurred, but fetal death and neonatal complications occurred in 12 of the 19 pregnancies in group 2. Four of the seven mothers in group 1 had complications; 16 of the 19 mothers in group 2 had complications. This study suggests that adrenalectomy during pregnancy should be considered as a therapeutic option in the management of Cushing's syndrome secondary to an adrenal cortical adenoma. PMID- 2247833 TI - The role of adrenalectomy in Cushing's syndrome. AB - Forty-four patients with Cushing's syndrome were treated by adrenalectomy between 1975 and 1989. Twenty patients had adrenal adenomas: 13 with obvious Cushing's syndrome and 7 whose disease was subclinical, detected after evaluation of an incidentally discovered adrenal mass (es). Twelve patients underwent bilateral adrenalectomies for Cushing's disease after failed transsphenoidal explorations and pituitary irradiation. Six patients had primary adrenal hyperplasia, five as manifestations of Carney's complex. Two others underwent bilateral adrenalectomies for ectopic adrenocorticotropic hormone from carcinoid tumors. Four patients had adrenocortical carcinoma treated with transabdominal adrenalectomy. Three are alive from 8 years to 5 months. There was one postoperative death (2.3%) caused by coagulopathy and multiple organ failure and three (7%) minor postoperative complications. Follow-up showed good to excellent results in 95% of patients. It is concluded that adrenalectomy provides prompt relief from the severe morbidity of Cushing's syndrome regardless of the cause. It is the treatment of choice for adrenal adenomas, carcinomas, primary hyperplasia, and selected patients with Cushing's disease. PMID- 2247834 TI - Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome. AB - The recovery time of the hypothalamic-pituitary-adrenal (HPA) axis after curative resection of adrenal tumors in patients with Cushing's syndrome is poorly documented. Eight consecutive patients were treated with a standardized hydrocortisone replacement strategy after curative resection of a cortisol secreting tumor and the time to recovery of the HPA axis was determined. Hypercortisolism was documented by elevated 24-hour urinary free cortisol levels. Cure was documented by undetectable postoperative morning serum cortisol levels. Each patient received replacement hydrocortisone after surgery and was reevaluated every 3 to 6 months with an adrenocorticotrophic hormone (ACTH) stimulation test. Each patient was also monitored carefully for symptoms and signs of adrenal insufficiency, which was defined as symptoms consistent with this diagnosis that responded to increases in hydrocortisone levels. After surgical resection, each patient was cured of hypercortisolism. Subsequently, despite replacement hydrocortisone, each patient had symptoms of hypocortisolism, and in four of eight patients the dose of hydrocortisone was increased to relieve the symptoms. Patients required a median time of 15 months (range, 9 to 22 months) to recover a normal ACTH stimulation test and 19 months (range, 12 to 24 months) to allow discontinuation of replacement doses of hydrocortisone. The results suggest that surgical resection of a cortisol-secreting adrenal tumor will result in rapid cure of hypercortisolism, but complete recovery of the HPA axis and discontinuation of replacement steroids will require between 1 and 2 years. Normal adrenal function, as assessed by the cortisol response to ACTH, returns despite replacement doses of hydrocortisone, and replacement doses of hydrocortisone can be tapered rapidly or discontinued after a normal ACTH stimulation test. PMID- 2247835 TI - Calcitonin gene-related peptide levels are elevated in patients with sepsis. AB - Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125 labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state. PMID- 2247836 TI - Posttranslational gastrin processing depends on tumor morphology. AB - Extracellular matrices have recently been demonstrated to alter cell morphology in culture. Altered cell morphology has been associated with changes in gene transcription and translation, but it is not known whether it also affects posttranslational processing. Using tyrosine-O-sulfation as a marker of processing, we studied the effects of various substrates on biologically active gastrin (IRG) production and sulfation in gastrin-containing tumor cells (GT cells). Dispersed GT cells were plated onto different substrates and then incubated. Culture media from days 4, 7, and 28 were assayed with specific antibodies that recognize total IRG and nonsulfated IRG. Cells cultured on plastic and dried films of laminin, collagen, and Matrigel (Collaborative Research Inc., Lexington, Mass.) flattened and formed monolayers of GT cells. Cells cultured on a porous membrane and hydrated gels of collagen and Matrigel did not flatten but formed spheroids of GT cells. The monolayer cultures showed an increase in sulfation with time but a decrease in IRG production. The spheroid cultures maintained a constant level of sulfation over time and, with the exception of Matrigel (gel), also showed a decrease in IRG production. These results indicate that the level of sulfation was unchanged from that of the original tumor when cells were grown in spheroids but increased when cultured as monolayers. It appears that alteration of the cellular milieu alters colony morphology, which in turn alters gastrin processing. PMID- 2247837 TI - Long-term results of adrenal autotransplantation in Cushing's disease. AB - Many advances have been made in the diagnosis and treatment of patients with Cushing's disease. Currently, partial or total transsphenoidal resection of the pituitary gland is the surgical approach favored by many authorities, with cure rates of 80% to 90% reported for selected patients. However, long-term follow-up is still needed for this treatment modality, and recurrence rates of up to 50% have been reported. In addition, less favorable results are seen with this approach when there is recurrence after initial transsphenoidal surgery or when there is not a single microadenoma responsible for the disease of the pituitary gland. We report a series of 14 patients who were treated with bilateral adrenalectomy and autotransplantation. Follow-up is 4 to 14 years. Four patients show iodocholesterol uptake at the site of autotransplantation. Of these, three patients have been weaned from cortisone for 12, 10, and 2 years. The fourth patient, after being weaned from all medications, underwent partial resection of a hyperfunctioning autotransplant and currently, 7 years after the original operation, is being weaned from cortisone. A fifth patient was weaned to a reduced dose of cortisone for 8.5 years, but the dose was recently increased. There is no evidence of Nelson's syndrome in any of these patients with clinical evidence of functioning autotransplants. We believe that bilateral adrenalectomy with autotransplantation still plays an important role in the long-term management of selected cases of Cushing's disease and that autotransplantation, when successful, results in few complications and allows long-term freedom from exogenous steroid medication. PMID- 2247838 TI - Direct proabsorptive effect of octreotide on ionic transport in the small intestine. AB - Somatostatin is widely distributed within the nervous system and the gastrointestinal tract. Gastrointestinal actions of somatostatin include inhibition of hormone release, reduction of pancreatic secretion, inhibition of motility, and reduction of blood flow. The purpose of this study was to investigate the role of somatostatin and its analogue octreotide on water and electrolyte transport in the small intestine. Rabbit ileal segments (n = 17) were harvested and arterially perfused ex vivo with a nonrecirculating oxygenated sanguineous solution. The lumen was perfused with an isotonic solution containing carbon 14-labeled polyethylene glycol. Net fluxes of water, Na+, and Cl- were calculated for three 20-minute periods designated basal, drug infusion, and recovery. Three groups were studied: somatostatin at 10(-6) mol/L (n = 5), somatostatin at 10(-5) mol/L (n = 5), and octreotide at 10(-5) mol/L (n = 7). Somatostatin at 10(-5) mol/L yielded a proabsorptive effect on the flux of water and electrolytes. Octreotide at 10(-5) mol/L caused a significant (p less than 0.05) proabsorptive response in the fluxes of water, sodium, and chloride during the period of drug infusion, which returned to basal secretory levels during the recovery period. This proabsorptive effect occurred without alterations in vascular resistance and necessarily was independent of systemic hormone interaction, supporting a direct effect of octreotide on intestinal ionic transport. PMID- 2247839 TI - The glands of Owen--a perspective on the history of hyperparathyroidism. PMID- 2247840 TI - Intraatrial extension of thyroid cancer: technique and results of a radical surgical approach. AB - An occlusion of the superior vena cava by a tumor thrombus extending into the right atrium was diagnosed in three patients with a follicular thyroid cancer. All patients showed the typical clinical picture of the superior vena cava syndrome. A right parasternal thoracotomy was performed for preparation of the major vessels. The superior vena cava was opened and the entire intravascular tumor thrombus was removed. The cavotomy was closed directly in two patients. In the third patient the left brachiocephalic trunk was resected and reconstructed with a vascular (polytetrafluoroethylene) graft. This patient had bone and brain metastases and an occlusion of the graft 3 months after surgery after anticoagulation was stopped. The other two patients were clinically symptom free without local recurrence 13 and 50 months after surgery. An aggressive surgical approach is justified in grossly invasive thyroid cancer to decrease local recurrence and death rates, to correct the disturbing clinical symptoms of superior vena caval occlusion, and to prevent tumor embolism and the development of distant metastases. By reducing tumor mass, an even better basis for radioiodine treatment can be prepared. PMID- 2247841 TI - The intraoperative incidence of detectable bilateral and multicentric disease in papillary cancer of the thyroid. AB - This is a prospective study to determine the incidence of grossly detectable multicentric and bilateral cancer at operation in patients who, before surgery, were believed to have a unilateral lesion. The opposite lobe was inspected at the time of operation and the surgeon made a determination as to whether there was bilateral and/or multicentric disease present. A total thyroidectomy was then carried out and the accuracy of the surgeon's judgment was established by permanent-section pathologic examination. Fifteen of the 44 patients were assessed to have gross bilateral disease. Thirteen of these were confirmed by pathologic examination. One case of microscopic bilateral disease was not recognized by the surgeon. Seventeen patients were thought to have unilateral multicentric disease. Fifteen of these cases were confirmed by microscopy and an additional seven cases were documented to have secondary foci. It is obvious from this study that most disease that is called microscopic disease is actually palpable. A review of the literature confirms this. It was very unlikely for a patient who did not have unilateral multicentric disease to have a contralateral focus of carcinoma. The incidence of bilateral disease was 32%, and the incidence of multicentric disease was 50%; the surgeon was very accurate in assessing this. We believe that surgeons who advocate lobectomy as the primary treatment for thyroid cancer are recognizing grossly detectable disease in a significant number of patients and thus are doing total thyroidectomies in most patients with bilateral disease. PMID- 2247842 TI - Intraoperative decision making during thyroid surgery based on the results of preoperative needle biopsy and frozen section. AB - Prognostic factors in well-differentiated thyroid cancer are age of the patient and grade, size, distant metastasis, and extracapsular spread of the disease. However, the surgeon is often not sure about the pathologic diagnosis of thyroid nodules. The accuracy of preoperative studies, such as ultrasonography and thyroid scanning, is limited. The most cost-effective test is fine-needle aspiration, the accuracy of which exceeds 80% in most series. However, a large group of nodules exist for which aspiration cytologic studies are considered to be either suspicious or indeterminate. The decision about the extent of thyroidectomy may be difficult in these patients. Intraoperative frozen section may help the surgeon to distinguish benign from malignant lesions, but as in fine needle aspiration, the major problem is the distinction between follicular adenoma and follicular carcinoma. The frozen section diagnosis of follicular adenoma was changed to follicular carcinoma in one third of the cases (13 of 38 cases). The decision about the extent of thyroidectomy in patients with follicular adenomas was based on other prognostic factors, such as age and sex of the patient and the size of the nodule. The accuracy of frozen section diagnosis was 95%. Our experience suggests that decisions regarding the extent of thyroidectomy can best be made by preoperative fine-needle aspiration with confirmation by frozen section diagnosis in equivocal cases. PMID- 2247843 TI - Prognostic significance of nondiploid DNA determined by flow cytometry in sporadic and familial medullary thyroid carcinoma. AB - To clarify the role of DNA measurements in predicting outcome after surgical treatment of medullary thyroid carcinoma (MTC), we performed flow cytometric analysis in nuclear suspensions of 119 MTC tumors. Of the 119 patients, 63 (53%) patients had sporadic tumors and 56 (47%) patients had familial tumors; survivors were followed for a mean of 13 years. DNA content was normal in 92 (77%) patients and abnormal (nondiploid) in 27 (23%) patients. Ten-year cause-specific mortality rates were 12%, 42%, and 49% with diploid, tetraploid/polyploid, or aneuploid tumors (p = 0.0009) and were greater with nondiploid tumors both in the sporadic (p = 0.012) and multiple endocrine neoplasia (familial) cases (p = 0.114). None of 27 patients with TNM stage I disease died of MTC. In patients with TNM stages II, III, and IV disease, DNA nondiploid tumors were associated with increased deaths from MTC. In a Cox proportional hazards model involving all 119 patients and adjusted for disease stage and inheritance pattern, nondiploid DNA was independently associated with increased deaths from MTC (p = 0.008). In an identical Cox model restricted to the 92 DNA diploid tumors, an S-phase fraction of 15.0% or more remained a significant variable (p = 0.034) after adjustment for stage and inheritance pattern. We therefore conclude that DNA measurements do have a role to play in predicting outcome after surgical treatment of MTC. PMID- 2247844 TI - Clinicopathologic and flow cytometric DNA study of medullary thyroid carcinoma. AB - Sixty-one patients with medullary thyroid carcinoma were investigated to establish relationships between the neoplasm's DNA content, other clinicopathologic factors, and patient survival (at least 5 years' follow-up). There were 26 (42.6%) familial and 35 (57.4%) sporadic carcinomas. Forty-two neoplasms (68.8%) were diploid and 19 (31.2%) were aneuploid by flow cytometric assessment. In univariate analysis, age, hereditary background, DNA content, calcitonin immunoreactivity, and type of surgery were strong predictors of clinical outcomes. In multivariate regression analysis, none of these factors was an independent prognosticator. Patients' gender, clinical stage, histologic subtype, and amyloid content of the tumor did not influence survival. PMID- 2247845 TI - Actin architecture of cultured human thyroid cancer cells: predictor of differentiation? AB - The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells. PMID- 2247846 TI - N-ras 61 oncogene mutations in Hurthle cell tumors. AB - Mutations of ras oncogenes are believed to play an important role in the initiation or progression of human tumors. In thyroid tumors the incidence of ras activation by specific point mutations has been reported to range from 33% in follicular adenomas up to 60% in anaplastic carcinomas. Because of our long standing interest in Hurthle cell tumors, we began a study of 70 such cases to determine the incidence of ras mutations and their clinical correlates. Analysis of N-ras sequences at codon position 61, with the polymerase chain reaction method and oligonucleotide probe hybridization, showed point mutations of the normal codon CAA* in eight tumor samples. One was a mutation from CAA to AAA, one from CAA to CTA,* and six from CAA to CGA. These mutations would result in amino acid substitutions of lysine, leucine, or arginine for the normal glutamine at position 61 in the N-ras protein. Identical ras mutations in two tumors and some of their surrounding thyroid tissue may indicate that activating ras point mutations are an early event in carcinogenesis. The incidence of mutations was 1 of 24 (4%) of the histologically benign tumors, 5 of 34 (15%) of the intermediate tumors (with vascular or capsular permeation), and 2 of 12 (17%) in the malignant group. Four of these eight patients died of metastatic thyroid disease and four are alive without evidence of recurrence. PMID- 2247847 TI - Directors' and officers' liability. AB - Charities or business associations frequently ask physicians--due to their status in the community--to serve as directors or officers. Just as frequently, physicians agree to serve in those positions without fully understanding the responsibilities and possible liabilities they are assuming. This article describes the duties of directors and officers and the liabilities associated with the job. PMID- 2247848 TI - Immunization status of chronically ill children. AB - The immunization status of 103 chronically ill children attending five specialty clinics, and 52 otherwise healthy children attending an acute care clinic, was determined using a questionnaire self-administered by parents. The immunization rate in specialty clinics was 72%, compared with 85% in the acute care clinic (P = 0.118). Only the neurology clinic rate (55%) differed significantly from the control (P = 0.014). In patients age 48 months or older, there was a significant association between clinics and overall compliance (P = 0.003). Older specialty clinic patients (79%) tended to be more compliant compared to their younger counterparts (60%) (P = 0.057). No significant association was noted between immunization compliance and source of primary care services or intensity of use of services. Greater efforts are needed to identify underimmunized chronically ill children and to provide the means to bring them into compliance. PMID- 2247849 TI - Anemia of chronic disease: a review of pathogenesis. AB - Although anemia of chronic disease is a common hematologic disorder, the pathogenesis of the disease is still not well understood. Various workers have demonstrated decreased red cell life span, decreased erythropoietin levels, and inappropriate response of the bone marrow to the degree of anemia. The iron metabolism in the anemia of chronic disease is abnormal in that the macrophages in the bone marrow hold onto iron and do not release it for reutilization by the erythroid precursors. More recent studies have focused attention on cytokines produced by macrophages. These are interleukin-1 and tumor necrosis factor. These cytokines appear to be involved in both red cell production and ferrokinetics. Greater understanding of the biology of the cytokines may be the key to understanding the pathogenesis of anemia of chronic disease. PMID- 2247850 TI - Cardiac surgery for inmates in the Texas Department of Corrections. AB - All Texas prison inmates requiring hospitalization since 1983 have been transferred to a separate prison hospital adjacent to a tertiary care university hospital. We reviewed and analyzed the data regarding one major tertiary care service, namely cardiac surgery, to describe the rate of utilization of this service and its results. From January 1, 1984, to June 30, 1988, 73 inmates underwent 74 cardiac operations, 50 of which were coronary revascularizations. The age-adjusted rates of utilization for coronary artery bypass grafting were substantially higher for inmates over age 45 than for that described for the general population, whereas the utilization rates for valve surgery were comparable. There were no perioperative or late deaths, and 86% of the inmate patients are currently employed within the Texas Department of Corrections system or were employed at the time of their release. The utilization rates and the results of this representative tertiary medical care service for the state's prison population are comparable to those achieved in the private sector, and may have a substantial beneficial effect on inmate rehabilitation. PMID- 2247851 TI - Effect of gene conversion on variances of digenic identity measures. AB - The variances and covariances of digenic descent measures are studied for a two locus model incorporating mutation, gene conversion, recombination, drift, and finite sampling. Gene conversion can occur between allelic pairs of genes or between non-allelic pairs on the same or different gametes within individuals. Most interest therefore centers on pairs of genes, and five digenic identity measures are required. The behavior over time of these measures is studied, with an emphasis on the effects of gene conversion. Because of the stochastic nature of the forces of drift, recombination, mutation, and conversion, the actual identity status of gene pairs can vary from expectation among replicate populations. To study this variation we compute the expected variances and covariances of the measures, and show that this requires the introduction of trigenic and quadrigenic measures. Allowing for conversion between genes on different gametes requires a large number of these higher-order measures. PMID- 2247852 TI - Evolution of the segregation ratio: modification of gene conversion and meiotic drive. AB - We compare the evolutionary pressures that direct the modification of gene conversion and meiotic drive at loci subject to purifying and overdominant viability selection. Gene conversion differs from meiotic drive in that modifers do not affect their own segregation ratios, even when linked to the viability locus. Segregation distortion generates gametic level disequilibria between alleles at the viability locus and modifiers of gene conversion and meiotic drive: enhancers of segregation distortion become positively associated with driven alleles. Suppression of gene conversion evolves if the driven allele is marginally disadvantageous (overdominant viability selection), and higher rates evolve if the driven alleles are relatively advantageous (purifying viability selection). Gametic disequilibria permit enhancers of meiotic drive that are linked to the driven locus to promote their own segregation. We attribute the failure of genetic modifiers of gene conversion and meiotic drive to maximinize mean fitness to the generation of such associations. PMID- 2247853 TI - Ethical and communal issues in AIDS: an introduction. PMID- 2247854 TI - AIDS and 'dirt': reflections on the ethics of ritual cleanliness. AB - AIDS and the responses and attitudes it evokes surpass the analytic abilities of standard bioethics. These responses and attitudes are explored in terms of literary and anthropological categories, such as dirt, disorder, pollution and ritual cleanliness. Implications for medical education are suggested. PMID- 2247855 TI - Negotiating criteria and setting limits: the case of AIDS. AB - The classification of clinical problems, such as AIDS, requires choices. Choices are made on epistemic (i.e., knowledge-based) and non-epistemic (i.e., action based) grounds. That is, the ways in which we classify clinical problems, such as AIDS, involve a balancing of different understandings of clinical reality and of clinical values among participants of the clinical community. On this view, the interplay between epistemic and non-epistemic interests occurs within the embrace of particular clinical contexts. The ways in which we classify AIDS is the topic of this paper. We consider the extent to which we construct clinical reality; we examine a suggested classification of AIDS; and we conclude suggesting that the choice regarding how to classify AIDS is the result of negotiation among participants in the clinical community. PMID- 2247857 TI - Ethics, AIDS, and community responsibility. AB - In the discussion of the responsibilities of society to the HIV infected and uninfected, a serious question seems to have been left out of the picture: To what extent are people who are not infected, have no special relationship to the infected and have no professional responsibilities for the care of AIDS patients under an obligation to come to the aid of people with the HIV? In this paper, I shall examine our responsibilities, as members of society, for the welfare of others to whom we may or may not have a special relationship. I shall argue that those responsibilities flow from the conditions that structure our transactions with others; conditions that make such transactions possible. PMID- 2247856 TI - HIV and the obligation to treat. AB - The paper is an attempt to review the basis for the claim that physicians have a professional obligation to treat AIDS patients. Considered are the historical record, two professional codes of ethics, and several recent articles. The paper concludes that the arguments considered, which attempt to support the claim that physicians have an obligation to treat, fail. It is suggested, rather, that common humanity, which physicians share with those who suffer from AIDS, ought to be the basis for engaging in the care of AIDS patients. PMID- 2247858 TI - The temporality of illness: four levels of experience. AB - This essay argues that, while much has been gained by medicine's focus on the spatial aspects of disease in light of developments in modern pathology, too little attention has been given to the temporal experience of illness at the subjective level of the patient. In particular, it is noted that there is a radical distinction between subjective and objective time. Whereas the patient experiences his immediate illness in terms of the ongoing flux of subjective time, the physician conceptualizes the illness as a disease state according to the measurements of objective time. A greater understanding of this disparity in temporal experiencing provides insights into the lived experience of illness and can preclude difficulties in communication between physician and patient. PMID- 2247859 TI - Fingarette on the disease concept of alcoholism. AB - Herbert Fingarette argues that alcoholism is not a disease and that the alleged alcoholic under certain circumstances has the power to control his or her drinking disorders. I shall analyze Fingarette's argument and show that his position rests on some logical and conceptual confusions. In analyzing Fingarette's argument for the self-control theory of drinking disorders I conclude that it is problematic for the following reasons: (1) his argument assumes that the identification of a single cause of alcoholism is a necessary condition of its being a disease; (2) unless it is already assumed (a priori) that persons with drinking disorders possess freedom and self-control to the extent that Fingarette assumes they do, then such persons are likely to suffer from apathy or defeatism regarding their condition; (3) even if Fingarette is correct in his criticism of certain health care programs for those with drinking disorders, it does not follow from this that certain theories about the possible causes of such disorders are false; (4) Fingarette's claim that those with drinking disorders are morally responsible for their actions that result from their disorders is problematic, that is, unless it can be shown that such persons act freely; and (5) Fingarette attempts to support the self-control theory of alcoholism by refuting a 'straw man' conception of the disease model of alcoholism. PMID- 2247860 TI - Alcohol breath testing in patients with respiratory disease. PMID- 2247861 TI - Pharyngeal shape and dimensions in healthy subjects, snorers, and patients with obstructive sleep apnoea. AB - To characterise the relation between pharyngeal anatomy and sleep related disordered breathing, 17 men with complaints of snoring were studied by all night polysomnography. Ten of them had obstructive sleep apnoea (mean (SD) apnoea hypopnoea index 56.3 (41.7), age 52 (10) years, body mass index 31.4 (5.3) kg/m2); whereas seven were simple snorers (apnoea-hypopnoea index 6.7 (4.6), age 40 (17) years, body mass index 25.9 (4.3) kg/m2). The pharynx was studied by magnetic resonance imaging in all patients and in a group of eight healthy subjects (age 27 (6) years, body mass index 21.8 (2.2) kg/m2, both significantly lower than in the patients; p less than 0.05). On the midsagittal section and six transverse sections equally spaced between the nasopharynx and the hypopharynx several anatomical measurements were performed. Results showed that there was no difference between groups in most magnetic resonance imaging measurements, but that on transverse sections the pharyngeal cross section had an elliptic shape with the long axis oriented in the coronal plane in normal subjects, whereas in apnoeic and snoring patients the pharynx was circular or had an elliptic shape but with the long axis oriented in the sagittal plane. It is suggested that the change in pharyngeal cross sectional shape, secondary to a reduction in pharyngeal transverse diameter, may be related to the risk of developing sleep related disordered breathing. PMID- 2247862 TI - Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output. AB - Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly. PMID- 2247863 TI - Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids? AB - When used in high doses, inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal axis. The influence of the mode of drug inhalation on the degree of this suppression is not clear. Hypothalamo-pituitary-adrenal function was assessed by measurement of 0900 h serum cortisol concentrations, a short tetracosactrin test, and 24 hour urine free cortisol excretion in 48 adults with asthma taking 1500-2500 micrograms beclomethasone dipropionate daily via a metered dose aerosol. Twelve patients had hypothalamo-pituitary-adrenal suppression, as judged by subnormal results from at least two of the three tests or (in one patient) by an abnormal insulin stress test response. These patients then changed to inhaling the same dose of beclomethasone dipropionate through a 750 ml spacer device (Volumatic). The endocrine tests were repeated from nine days to eight weeks later in 10 patients. Comparison with initial values showed that adding the spacing device caused an increase in the median 0900 h cortisol concentration from 126 nmol/l to 398 nmol/l, in the post-tetracosactrin cortisol concentration from 402 nmol/l to 613 nmol/l and in 24 hour urine free cortisol excretion from 54 nmol to 84 nmol. The rise in serum cortisol concentration in response to tetracosactrin did not change. Evidence of persisting hypothalamo pituitary-adrenal axis suppression was present in only four of the 10 patients; the most pronounced improvements in function tended to occur in those who had never required long term oral corticosteroids. The results from this uncontrolled study suggest that asthmatic patients taking high dose beclomethasone dipropionate may minimise adverse effects by using a large volume spacer device. PMID- 2247864 TI - Morning serum cortisol concentrations after 2 mg inhaled beclomethasone dipropionate in normal subjects: effect of a 750 ml spacing device. AB - Large spacing devices have been shown to provide more selective delivery of an inhaled steroid to the lung but the effect on the hypothalamo-pituitary-adrenal suppression associated with high dose inhaled corticosteroids has been little studied. The effect of a large spacing device (Volumatic; 750 ml) on suppression of 0900 h cortisol after 2 mg inhaled beclomethasone dipropionate was therefore investigated in normal, healthy volunteers. Twenty four subjects (12 male, 12 female) took part in a randomised, double blind, placebo controlled cross over study in which a single dose of 2 mg beclomethasone dipropionate was taken at 2300 h on two occasions seven days apart, once from a metered dose inhaler alone and once from a metered dose inhaler attached to a 750 ml spacing device. The 0900 h serum cortisol concentration was the same on the morning before each administration (468 nmol/l, 95% confidence interval (CI) 390-561 nmol/l, day 1 v 479 nmol/l, 95% CI 463-494 nmol/l, day 8). The 0900 h serum cortisol concentration the following morning, however, was lower when 2 mg beclomethasone dipropionate was given by metered dose inhaler alone (182 (95% CI 128-264) nmol/l) than when it was given by a spacing device (363 (95% CI 281-475) nmol/l). These results suggest that a large spacing device attached to a metered dose inhaler may decrease the risk of hypothalamo-pituitary-adrenal suppression by high dose inhaled steroid treatment. PMID- 2247865 TI - Role of small calibre chest tube drainage for iatrogenic pneumothorax. AB - A 2 mm Teflon catheter was used as a chest tube in 28 patients with iatrogenic pneumothorax. Frequent aspirations through the catheter were performed in 16 of the patients. In the remaining 12 patients the catheter was connected to a one way flutter valve. The treatment was successful in 27 of the 28 patients--one patient required a large calibre chest tube. The mean drainage time was 48 hours. The small catheter technique is superior to the use of a large intercostal drain as it is much less traumatic and troublesome. The small calibre chest tube with a one way valve is recommended as a safe and easy technique. PMID- 2247866 TI - Respiratory muscle function in cystic fibrosis. AB - Maximal static expiratory and inspiratory mouth pressures (PEmax and PImax) and quadriceps femoris muscle strength were measured in 25 patients aged 16-28 years with cystic fibrosis (mean FEV1 46% predicted). Mean (SD) PEmax was 64% (18%) predicted (below 75% predicted in 16 of the 25 patients), and PImax was 64% (24%) predicted (below 75% predicted in 14 patients). Quadriceps muscle strength was 68% (20%) predicted (below 75% predicted in 17 patients). The relatively small reduction in respiratory muscle strength in these patients was unlikely to have contributed appreciably to their respiratory problems. PMID- 2247867 TI - Assisted ventilation. 1. Artificial ventilation: history, equipment and techniques. PMID- 2247869 TI - Granulomatous Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome. AB - A patient with an unusual granulomatous response to infection with Pneumocystis carinii is described. The diagnosis was made by open lung biopsy after two negative bronchoalveolar lavages. PMID- 2247870 TI - Bronchoalveolar lavage via a modified stomach tube in intubated patients with the acquired immunodeficiency syndrome and diffuse pneumonia. AB - A simple non-bronchoscopic bronchoalveolar lavage method was used in 30 patients with the acquired immunodeficiency syndrome undergoing assisted ventilation for respiratory failure. A modified Argyle Levin stomach tube was passed via the endotracheal tube and lavage performed. The lavage was well tolerated and performed quickly and easily, required little training, and had a high degree of sensitivity (73%--a diagnosis in 22 of the 30 cases). PMID- 2247868 TI - Molecular biology and respiratory disease. 7. The alpha 1 antitrypsin gene and chronic lung disease. PMID- 2247871 TI - Posterior mediastinal teratoma with abdominal extension. AB - Posterior mediastinal benign teratomas are uncommon neoplasms in infancy; nine cases have been reported so far. A one month old baby was found to have a benign posterior mediastinal teratoma infiltrating the lower oesophagus from the level of the carina through the oesophageal hiatus into the upper abdomen. Partial oesophagectomy provided a successful outcome. PMID- 2247872 TI - Giant lymph node hyperplasia of the lung (Castleman's disease) associated with recurrent pleural effusion. AB - A case of giant lymph node hyperplasia (Castleman's disease) of the lung presented with pleural effusion (which was recurrent), an unusual complication. The patient was treated with pneumonectomy and has survived for three years without relapse. This is the first report of the disease from black Africa. PMID- 2247873 TI - Investigation of pulmonary disease in HIV infection. PMID- 2247874 TI - British Thoracic Society summer meeting. 11-13 July 1990, Birmingham. Abstracts. PMID- 2247875 TI - [Pathogenesis and pathophysiology of carnitine deficiency, a predictable risk]. AB - When patients suffer from hepato-encephalopathy, (cardio)myopathy, dystrophy, hypoglycaemia, some metabolic diseases and several other disease states, carnitine deficiency should be considered. In this article a survey is given of the pathophysiology, laboratory diagnostics, clinical symptomatology and some therapeutic approaches. Some different cases will be demonstrated. PMID- 2247876 TI - [Neonatal meningitis caused by Enterobacter sakazakii: milk powder is not sterile and bacteria like milk too!]. AB - Powdered milk for infants can contain very low numbers of Enterobacter sakazakii. Larger amounts of this organism can result in non-infective colonization. In infants, particularly the premature newborn, such colonization has been associated with abdominal distention and bloody diarrhoea or bacteriuria, but cases of sepsis and meningitis have also been reported. Infection has been associated with the use of contaminated spoons or blenders as well as the habit of keeping the ready-made milk hot in bottle-heaters. The risk of contamination of the milk can be eliminated by boiling bottles, teats and spoons as well as disinfecting the blender before use. The possibility of bacterial replication can be significantly reduced by keeping the ready-made milk in a refrigerator and warming it up immediately before use eg by using a microwave oven. PMID- 2247877 TI - [Fetal and neonatal outcome prolonged ruptured membranes in a gestational age of less than 24 weeks]. AB - The view appears to be generally held that the survival chances of fetuses in cases of very early rupture of the membranes are low. We report a retrospective study of 12 pregnancies with prolonged rupture of the membranes less than or equal to 24 weeks menstrual age. There was no significant maternal morbidity. After birth special attention was given to respiratory problems, deformities and infections. Four children were born at menstrual age less than 26 weeks. In all cases an intrauterine infection was found (chorioamnionitis). The eight children born greater than or equal to 26 weeks had good chances of survival despite oligohydramnios (all) and deformities (four). Severe intrauterine infections were not present in this group. An expectant obstetric management in cases of very early prolonged rupture of the membranes seems justified. PMID- 2247878 TI - [Early diagnosis of fragile X mental retardation syndrome]. AB - Conducting an inquiry among 32 parents of 46 children with fragile-X mental retardation, we investigated the problems on early recognition of the syndrome. From the first call for medical help until establishment of the diagnosis, on average 2 years elapsed. The family history is very important, since in 82.5% of the cases mental retardation also occurred in other family members. We recommend that investigations should be performed in all children who do not repeat words and/or do not walk without help, at the age of 18 months. A high priority must then be given to specific investigations on the X-chromosomal fragile site. PMID- 2247879 TI - [Minor seizures in young children: epileptic or not?]. AB - In 80 children the clinical features of sudden changes of consciousness, motor activity and/or behavior were studied retrospectively. Epileptic and non epileptic seizures could not be separated because of specific clinical characteristics in this population, although breath holding spells have some rather distinguishing features. The greatest problem was the lack of detailed clinical information in many cases. A group of children remains with paroxysmal events of unknown origin, but from this material the prognosis of them seems to be good. The clinician should be able to differentiate epileptic from non epileptic seizures by taking a careful history based upon a detailed knowledge of the different kinds of both epileptic and non-epileptic attacks. PMID- 2247880 TI - [CRP versus BSE in pediatrics. How good is a diagnostic test?]. AB - In a prospective study CRP and BSE values were compared in 130 children who came to the first aid of our hospital with symptoms suspicious for an infection either viral or bacterial. Since the predictive value of both parameters dependents on the prevalence of diseases we discussed the likelihood ratio and the receiver operating characteristic as better parameters in the evaluation of a test i.e. BSE and CRP. It finally became clear that such characteristics are useful in clinical practice and therefore deserve more attention. PMID- 2247881 TI - [A child with neonatal allo-immune neutropenia]. AB - A newborn child with neonatal neutropenia as a result of the presence of maternal IgG isoantibodies against neutrophil granulocyte blood group antigens is reported. Mechanism, diagnostics and therapy of the disease are discussed. The diagnosis not only has consequences for the child, but also for the mother and following pregnancies. A review of the most important causes of neonatal neutropenia is given. PMID- 2247882 TI - [Generalized candidiasis in a prematurely born infant]. AB - A male neonate born after spontaneous labor during the 25 3/7 week of gestation, developed a fatal course of disseminated candidiasis. Disseminated candidiasis is seen in newborns undergoing intensive care and has a high mortality rate. Important etiologic factors are low immunologic response, invasive monitoring techniques, systemic antibiotics and parenteral nutrition. Early diagnosis and efficient antimycotic therapy with amphotericin B and if necessary combined with flucytosine contribute a great deal to the chance of survival. PMID- 2247883 TI - Two-disease-locus model: segregation analysis using information on two markers in nuclear families. Application to IDDM. AB - In the present paper, an extension of segregation analysis is proposed using information on the joint segregation of two unlinked markers conditional on the disease status in nuclear families, in order to consider two-locus models with one locus linked to the first marker and the other linked to the second marker. We propose tests for examining evidence for the effect of genes located at these two loci and whether this effect is multiplicative or not. This method is then applied to a sample of IDDM families typed for the HLA and Gm markers to test, in addition to a factor of the HLA region, the potential involvement of the Gm system in the susceptibility to IDDM. The analysis does not provide evidence for such an involvement. PMID- 2247884 TI - Large haplotype-specific differences in inter-genic distances in human MHC shown by pulsed field electrophoresis mapping of healthy and type 1 diabetic subjects. AB - Type 1 diabetes is associated with extended haplotypes defined by combinations of specific alleles of genes in the MHC. We have used pulsed field gel electrophoresis mapping to examine the gross structure of the Class II region of the MHC and its relationship to susceptibility to Type 1 diabetes. We have studied heterozygous members of a family in which susceptibility to Type 1 diabetes is associated with an A1/B8/DR3 haplotype and resistance with A2/B7/DR2, an unrelated diabetic DR3,4 patient and a healthy DR4,w10 subject and a DR2/Dw2 cell line. Digestion was performed with the enzymes Sst II, Mlu I, and Pvu I and hybridization with 21-hydroxylase, DRA, DQB, DOB and DPA probes. Within the DQ/DR region the DR4- and DR7-bearing haplotypes studied contain insertions of 140 150kb relative to the DR3 haplotypes whilst the DR2 haplotype in the family was smaller than the DR3 haplotypes by 130kb, whilst that in the cell line was smaller by up to 220kb. This cell line, previously thought to be homozygous by consanguinity, was also shown to be heterozygous in the DP region. Although no differences between diabetic and healthy subjects were observed within the family, these differences in long-range structure may be of importance to the etiology of Type 1 diabetes, as well as to the evolution of the MHC. PMID- 2247886 TI - Familial alopecia areata: no linkage with HLA. AB - HLA antigens of two Jewish families with alopecia areata were studied. There was no linkage between the disease and the HLA complex. PMID- 2247885 TI - A novel human leucocyte surface membrane antigen defined by murine monoclonal antibody. AB - A murine monoclonal antibody has been produced which identifies a novel human leucocyte differentiation antigen. The antibody, designated WM-66, of IgM subclass, was cytolytic with human complement. WM-66 was shown to react with virtually all normal T and B lymphocytes from peripheral blood and lymphoid tissues, as well as blood monocytes and approximately 40% of bone marrow mononuclear cells. The antibody also bound to the majority of cases of chronic B cell malignancies, including chronic lymphatic leukaemia and non-Hodgkin's lymphoma, but not to cases of acute leukaemia or to the majority of leukaemic and lymphoblastoid cell lines. WM-66 also reacted with epithelium of bronchus and salivary gland ducts. A single band of relative molecular mass 65,000 Daltons was immunoprecipitated from membrane extracts of normal lymphocytes and the B-cell line Daudi. Treatment of a number of WM-66-negative B-cell lines with neuraminidase resulted in WM-66 binding, indicating that the antigen exists in a covert form masked by sialic acid residues on a wider spectrum of cell types than was initially apparent. The reactivity pattern of WM-66 indicates that it recognises a previously undescribed surface membrane molecule with broad non lineage-specific distribution on leucocytes. This has recently been confirmed at the Fourth International Workshop on Human Leucocyte Differentiation Antigens. Although the biological function of the molecule recognised by WM-66 is unknown, the lytic properties of the antibody suggest a possible in vivo therapeutic role as an immunosuppressant or for treatment of lymphoid malignancy. PMID- 2247887 TI - Immunohistological patterns of blood group ABO and type 1 chain (Lewis a Lewis b) and type 2 chain (H-2, Y) antigens in normal uterine cervix. AB - Ten monoclonal antibodies and one lectin were used to study the localization and distribution of Blood Group ABH, type 1 chain (Lewis a, Lewis b) and type 2 chain (H-2, Y) antigens in 22 cases of normal uterine cervix, with known ABO and Lewis phenotype and secretor status. The results showed that ABH isoantigen expression is clearly related to the secretor status. It is positive in the endo- and exocervical epithelium of secretor individuals and negative in non-secretors. Lewis antigen expression in both endocervical and exocervical epithelium is related to the patient's Lewis phenotype and is clearly controlled by the secretor gene. Indeed, the expression of the Lewis a antigen is limited to the tissue of people of Lewis (a + b-) phenotype (non-secretors), and the expression of Lewis b antigen is limited to the tissue of people of Lewis a-b+) phenotype (secretors). The Y antigen showed a focal expression in endocervical mucosa in all the cases, independently of secretor status or Lewis phenotype. The same pattern was observed for H-type 2 antigen, though only in secretor individuals. PMID- 2247888 TI - Decreased levels of IL-1 alpha and beta in psoriatic lesional skin. AB - Interleukin 1 (IL-1), which mediates a wide range of biological activities, is thought to play an important role in many inflammatory and immunologic diseases. Normal human epidermal keratinocytes constitutively produce IL-1. Based on our previous data indicating decreased IL-1 activity in psoriatic scale extracts, in the present study, we measured immunoreactive IL-1 alpha and beta levels in the suction blister fluids as well as in the psoriatic scale extracts using enzyme immunoassay for IL-1 alpha and beta. The results showed that although similarly low levels of IL-1 alpha were detectable in the suction blister fluid from normal and psoriatic lesional skin, and that no IL-1 beta was found in most of the blister fluids, indicating that IL-1 alpha is major IL-1 species produced by human skin. As compared to those in the blister fluids, IL-1 alpha levels in the horny tissue extracts were found to be much higher, and they were significantly higher in the orthokeratotic stratum corneum extracts than in the psoriatic scale extracts. However, gel filtration of the orthokeratotic horny tissue extracts demonstrated that constituents for immunoreactive IL-1 alpha and beta were quite variable depending upon the source of the horny tissues. The present study has confirmed that IL-1 levels in the psoriatic scale extracts are decreased when compared with those in the orthokeratotic horny tissue possibly due to an increased epidermal proliferation activity associated with its high turnover rate. The role of IL-1 psoriatic lesions remains unknown. PMID- 2247889 TI - Detection of three sialylated tumor-associated antigens in malignant serous effusions. AB - One hundred thirty-seven fluid samples from patients with malignant diseases, including 58 with lung cancer and 36 with gastric carcinoma, were screened for three tumor-associated carbohydrate antigens. The antigens tested were sialylated Lewis (SLEX) antigen, sialylated SSEA-1 (SLX) antigen, and sialylated Lewis (CA19 9) antigen. Thirty-four fluid samples from patients with benign diseases including 20 with tuberculous pleurisy were also tested for these three antigens as a control. SLEX antigen had the highest positivity rate among the three antigens both in the pleural effusions of patients with pulmonary adenocarcinoma and for all types of lung cancer (64.1% and 46.6%, respectively). In cancers of digestive system, the percentage of SLEX positivity was almost same as that for CA19-9, and higher than that for SLX. A combination assay using the three antigens resulted in an increased rate of detection of tumor-associated antigens (68% of 58 lung cancers including 83% of 39 adenocarcinomas, as well as 77% of 63 digestive system cancers including 84% of 36 gastric carcinomas). Gel filtration of pleural effusions or bile using sephacryl S-1000 showed that these three antigens were eluted in the void volume, indicating a molecular weight of greater than 2 X 10(6). Thus, all 3 antigens possibly exist on carrier protein with a high molecular weight. These observations suggest the potential application of these antigens to distinguish between benign and malignant fluid, and to monitor the effects of the treatment of various types of cancer. PMID- 2247890 TI - Myocardial preservation: a comparison of oxygenated crystalloid and blood cardioplegia. AB - The purpose of this experiment was to compare myocardial protective effect after global ischemia using oxygenated crystalloid (CCcO2) and an oxygenated blood (BCcO2) cardioplegic solutions. Post-ischemic ventricular performance was studied in 2 equal (n = 7) groups of dogs subjected to 120 min of global ischemia induced at average myocardial temperatures of 8 degrees C in the CCcO2 group and 18 degrees C in the BCcO2 group. Left ventricular (LV) function included analysis of LV systolic function (global and regional function), LV diastolic function (chamber and myocardial stiffness) and LV relaxation was measured by sonomicrometry and Millar micrometers. Data were processed with a Dec PDP-11/23 computer. In vitro oxygen content (Vol%) measured 3.2 +/- 1.0 (CCcO2) and 9.5 +/- 0.3 (BCcO2). Percent recoveries of LV global function (LVSP, loop area, % shortening, LV dp/dt, mean VCF and E max) in the CCcO2 group were approximately the same as those in the BCcO2 group. There were no significant differences in LV regional function (loop area and % shortening) after ischemia between the two groups. The chamber and myocardial stiffness after ischemia in the CCcO2 group were almost the same as the baseline values. Values in the BCcO2 group were reduced significantly compared to the baseline level. There were significant differences in post-ischemic chamber and myocardial stiffness between the two groups. Post-ischemic maximum negative LV dp/dt in both groups decreased significantly compared to the baseline values. However, the time constant and diastolic interval after ischemia in both groups were approximately the same as the baseline values. We conclude that there were no significant differences in myocardial protective effect between the CCcO2 and BCcO2 groups, and both methods preserved the ischemic myocardium well. PMID- 2247892 TI - The inhibitory factors of hematopoiesis in chronic hemodialysis patients treated with recombinant human erythropoietin. AB - In order to clarify possible factors responsible for varying responses in uremic patients treated with recombinant human erythropoietin (rHuEPO), we determined the inhibitory effects of ten uremic sera on the erythroid progenitors (CFU-E) and erythroid bursts (BFU-E). We also measured plasma EPO titers, Fe, UIBC, ferritin, PTH-C, beta 2-microglobulin, and aluminum in all ten patients. The inhibitor of CFU-E but not BFU-E, was present in the serum of the single anemic patient whose recovery took longer after the administration of rHuEPO. He did not have such conditions as iron deficiency, excess of aluminum, or chronic inflammation. The remaining patients, who had no CFU-E or BFU-E inhibitors, were good responders to rHuEPO. In none of ten patients were there inhibitors of granulocyte-macrophage progenitors (CFU-GM) or any differences in the other parameters. Although the inhibitory factor of CFU-E can be overcome with a larger dose, its prior determination may be useful to set out minimal effective dose of EPO treatment. PMID- 2247891 TI - Quantitation of IgG subclass antibodies to pneumococcal capsular polysaccharides by ELISA, using Pneumovax-specific antibodies as a reference. AB - A quantitative enzyme-linked immunosorbent assay (ELISA) method has been developed to assay the levels of IgG subclasses to pneumococcal capsular polysaccharides (PCP) by using a reference standard. This standard solution containing specific antibodies to a polyvalent pneumococcal vaccine (Pneumovax) was purified from the serum of an immunized healthy adult by affinity chromatography. In order to determine the predominant response to Pneumovax in the four IgG subclasses, specific IgG subclasses in preimmune and postimmune sera from six healthy adults were assessed quantitatively by the ELISA. With regard to peak concentrations after immunization, there was a marked increase in the IgG2 subclass, compared with those of IgG1 and IgG3. Such a quantitative assay of Pneumovax-specific IgG subclass antibodies is useful for the direct evaluation of immune responses to immunization with a polyvalent pneumococcal vaccine, and at the same time, for estimating the IgG2 response to PCP antigens in individuals. PMID- 2247893 TI - Beneficial effects of low-flow perfusion resumed early after zero-flow ischemia on myocardial energy metabolism and mechanical function: 31P-NMR study in the isolated perfused rat heart. AB - Effects of low-flow perfusion after zero-flow ischemia on myocardial mechanical function and energy metabolism were studied with 31P nuclear magnetic resonance spectroscopy, using isolated perfused rat hearts. After control perfusion, hearts were randomly divided into five experimental groups: Groups I and II were subjected to zero-flow ischemia of 40 and 60 min, respectively. In groups III-V the perfusion was resumed at a rate of 0.1 ml/min after 40 (group III), 30 (group IV) and 20 (group V)-min of zero-flow ischemia in order to compare the effects of low-flow perfusion with those of persistent zero-flow. After these interventions all the hearts were perfused for 40 min at a normal flow rate. Compared with the hearts exposed to total ischemia of 60 min, the preservation of high energy phosphate compounds (HEP) was better in groups with early low-flow perfusion; Creatine phosphate (CrP) levels, which had decreased rapidly after induction of zero-flow ischemia, increased gradually after initiation of the low-flow perfusion and reached significantly higher levels at the end of ischemic period in groups IV and V than in group II (p less than 0.05). The decrease in adenosine triphosphate (ATP) was likewise significantly suppressed by low-flow perfusion (groups IV and V greater than group II). Restoration of CrP levels after complete reperfusion was also significantly greater in group V than in group II. The recovery of ATP after complete reperfusion was also much better in group V being comparable to those in group I, although the total duration of ischemia was longer in group V than in group I. These results indicate the beneficial effects of low-flow perfusion on the preservation during ischemia and recovery after reperfusion of myocardial HEP. PMID- 2247894 TI - Increase in hematocrit by nifedipine in hypertensive patients. AB - The hematocrit, hemoglobin, serum total protein and serum albumin concentration increased significantly following sublingual administration of nifedipine in patients with essential hypertension (p less than 0.05). The mean increase in hematocrit at 60 min after administration was 1.5%. The results suggest a decrease in plasma volume, perhaps due to diuresis and a shift of fluid from the intravascular to the extravascular space. PMID- 2247895 TI - Production of monoclonal antibodies against recombinant HBcAg. AB - Three monoclonal antibodies against recombinant HBcAg were obtained from hybridomas fused between mouse myeloma line NS1 and splenocytes of immunized Balb/C mice. They specifically bound to recombinant HBcAg. Subtypes of these monoclonal antibodies were IgM and IgA. PMID- 2247896 TI - Selenium contents in human gallbladder bile. AB - The selenium contents in human gallbladder bile were analyzed. Thirty-seven subjects were studied; 22 patients with cholelithiasis in Niigata Prefecture and 15 patients (13 with cholelithiasis and 2 with gallbladder polypus) in Kochi Prefecture. Five ml of bile was withdrawn with a syringe from the gallbladder during the operation and stored at -20 degrees C until analysis. For the analysis by gas chromatograph with an electron-capture detector, 0.2 ml of sample was used. The mean selenium contents in bile were 269 +/- 39.0 (mean +/- S.D.) ng/ml for the subjects in Niigata and 285 +/- 84.4 ng/ml in Kochi; without significant difference. Of 37 samples analyzed, the mean content was 276 +/- 61.0 ng/ml. PMID- 2247897 TI - Managing accounts receivable: an overview. PMID- 2247898 TI - Outpatient front office functions. PMID- 2247899 TI - Back office functions of the billing process. PMID- 2247900 TI - Departmental interaction. PMID- 2247901 TI - Inpatient front office functions. PMID- 2247902 TI - Information systems support of accounts receivable process. PMID- 2247903 TI - Application to physicians' groups. PMID- 2247904 TI - The 1990s and beyond. PMID- 2247905 TI - Health care financing note. Selling receivables to raise cash--an inexpensive financing tool. PMID- 2247907 TI - Ultrastructural observations on Penicillium marneffei in natural human infection. AB - The ultrastructure of Penicillium marneffei and the host response to the infection were studied in two patients. One was immunocompetent and the other an immunosuppressed renal graft recipient. In the immunocompetent patient it was observed that all the yeast cells were phagocytosed and were found either within membrane-bound vacuoles or lying freely within the cytoplasm of the macrophages. It was postulated that continuous lysosomal fusion with the phagolysosomes and multiplication of the fungi within the phagocytic vacuoles might eventually lead to the rupture of the vacuoles with release of the organisms into the cytoplasm of the macrophages. In the second patient, the immunosuppressive effects of corticosteroids might account for the large number of nonphagocytosed fungi in the tissue space, and the failure to form large phagocytic vacuoles. PMID- 2247906 TI - Unusual primary lung neoplasms: spindle cell and undifferentiated lung carcinomas expressing only vimentin. AB - Two unusual primary carcinomas of the lung are described. One occurred in a 31 year-old man and was composed of large, undifferentiated, ovoid to polygonal cells. The other occurred in a 72-year-old man, was composed of spindle-shaped cells, and was initially diagnosed as a localized fibrous mesothelioma. The neoplastic cells of these tumors expressed only vimentin intermediate filaments and showed no other immunohistochemical features of epithelial neoplasms, although they exhibited a metastatic pattern characteristic of lung carcinomas. These two malignant neoplasms further expand the spectrum of unusual lung neoplasms, and suggest that there are pulmonary carcinomas that contain only vimentin intermediate filaments. PMID- 2247908 TI - A primary pleural tumor. PMID- 2247909 TI - Microcrystals in microcrystal-associated arthropathy (UP10:395-400, 1986) PMID- 2247910 TI - Malignant mediastinal tumor in a 9-year-old girl (UP11:793-799, 1987) PMID- 2247911 TI - Carcinoma in situ of penis. Is distinction between erythroplasia of Queyrat and Bowen's disease relevant? PMID- 2247912 TI - Are three substages of clinical B prostate carcinoma useful in predicting disease free survival? AB - The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well differentiated grade and a normal acid phosphatase, to have the longest interval to progression. PMID- 2247913 TI - Transrectal sonographic cystourethrography: studies in stress urinary incontinence. AB - Transrectal ultrasonic sagittal transducer is an excellent modality to image the bladder and urethra in dynamic change. In female patients, we found it is also helpful for the diagnosis of urinary stress incontinence. The posterior urethrovesical (PUV) angle is measured with the transrectal sonoprobe under strain and non-strain conditions. We compared the results of sonographic cystourethrogram with the radiographic chain cystourethrogram. The sonographic cystourethrography is superior to the radiography. The former may estimate the PUV angle accurately and differentiate between the patients with and without stress urinary incontinence. Furthermore, we also use the transrectal sagittal probe intraoperatively to adjust the suspension force as well as PUV angle in patients who underwent vesical neck suspension for stress urinary incontinence (SUI). PMID- 2247914 TI - Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer. A fifteen-year follow-up. AB - A fifteen-year follow-up of a prospective, randomized study comparing placebo with radical prostatectomy as the primary treatment of early prostatic cancer is presented. A total of 111 patients with clinical Stage I or II prostatic cancer, normal acid phosphatase levels, and negative findings on skeletal x-ray film were evaluable. Thirty Stage I patients and 20 Stage II patients received placebo only; 31 Stage I and 30 Stage II patients underwent radical prostatectomy. The survival status for 95 patients (86%) was established at the fifteen-year follow up. No significant differences in crude survival occurred in either stage or in both stages combined. Moreover, the survival curves closely followed reference curves based on expected U.S. mortality for men of comparable ages and races. A statistically significant association between a high Gleason histologic score and poor survival was established. In this study, initial treatment with radical prostatectomy did not yield longer survival than initial placebo treatment alone. However, the findings should be interpreted with caution, since sample size was small and staging procedure was simplified. PMID- 2247915 TI - Role of serum prolactin determination in evaluation of impotent patient. AB - Hyperprolactinemia is a recognized cause of impotence. The discovery of elevated prolactin levels in impotent men is very important since pharmacotherapy in this instance is highly successful. We review our experience with prolactin determinations in impotent men, and a population is defined that may benefit from routine prolactin determination. In our experience, the predominant symptom associated with hyperprolactinemia in men is loss of libido. PMID- 2247916 TI - Clinical experience implanting an inflatable penile prosthesis with controlled expansion cylinder. AB - Ninety-four patients with erectile dysfunction underwent implantation of controlled-expansion inflatable penile prosthetic cylinders. Most of these patients had aneurysmal dilatation of the corpora cavernosa after prior implantation of inflatable devices. Follow-up of forty-six months has shown their efficacy to be excellent for management of primary impotence, penile straightening procedures, and revision after cylinder leaks. None of the patients has had recurrence of the primary condition that required revision. PMID- 2247917 TI - Experience with Duraphase penile prosthesis: its use as replacement device. AB - The Duraphase Penile Prosthesis is a new, articulating type of semirigid prosthesis which appears to have several advantages over other semirigid penile prostheses. This series describes the experience with this prosthesis in 12 patients and highlights the experience in 4 patients who underwent removal of other types of prostheses due to mechanical or functional problems and replacement with the Duraphase prosthesis. The device has been mechanically reliable during short follow-up, and there has been excellent patient satisfaction. PMID- 2247918 TI - Retrograde transurethral balloon dilation of prostate: innovative management of abacterial chronic prostatitis and prostatodynia. AB - Retrograde transurethral balloon dilatation (RTBD) of the prostate recently has been suggested as alternative therapy for patients with benign prostatic hyperplasia (BPH). Seven patients with documented functional urinary outlet obstruction at the level of the bladder neck or prostatic urethra underwent RTBD of prostate. Each patient had a classic diagnosis of abacterial chronic prostatitis or prostatodynia based on history, physical examination, and localization cultures. Prior to RTBD of prostate, patients underwent cystoscopy, voiding cystourethrogram, urodynamic and uroflow studies. RTBD of prostate was done as an outpatient procedure requiring intravenous sedation or general anesthesia. Dilation was performed with a 25-mm urethroplasty balloon catheter inflated at 3.5 atm of pressure for twenty minutes. Improvement in voiding symptomatology was noted in all patients and graded numerically (0-10 scale), with ten indicating normal voiding. Follow-up to date ranges from one to five months. This technique may have promise as a treatment option in patients with abacterial chronic prostatitis and prostatodynia. PMID- 2247919 TI - Continence level following radical prostatectomy. AB - The relationship of the urethral anastomosis and postoperative continence following radical prostatectomy is uncertain. The objective of this study was to determine radiographically the functional level of continence following radical prostatectomy relative to the site of the intraoperative urethral anastomosis. In 8 patients having a radical prostatectomy, an intraoperative hemoclip was placed at the site of the urethral anastomosis and the postoperative functional level of continence was determined using a standing lateral cystogram. The functional level of continence was 9 mm (SD = 3.0) distal to the site of the urethral anastomosis. The level in the urethra that continence occurs may be a function of the intrinsic continence parameters of each individual patient. PMID- 2247920 TI - Acute urinary retention in a child with appendiceal abscess: diagnostic dilemma. AB - Rarely do children with appendiceal abscess present with acute urinary retention as the only sign or symptom. This presentation may delay diagnosis and definitive therapy, thereby causing additional morbidity and possible mortality. We report the eighth case of acute urinary retention in a child associated with an appendiceal abscess. PMID- 2247921 TI - The overlooked, retained Double J stent. AB - A series of 4 patients with long overlooked, retained ureteral stents is presented to illustrate the variable, unpredictable, and at times, hazardous course of such patients. These cases are cited to re-emphasize the need for careful documentation, observation, and follow-up of patients in whom stents are placed. PMID- 2247922 TI - Primary lymphoma of prostate: transrectal ultrasonic appearance. AB - In the case presented, primary lymphoma of the prostate was diagnosed by ultrasonically guided transrectal biopsy. Primary lymphoma of the prostate should be included in the differential diagnosis of a hypoechoic lesion found on ultrasonic evaluation of the prostate in a young adult. PMID- 2247923 TI - Transitional cell carcinoma of renal pelvis with multiple cerebral metastases. PMID- 2247924 TI - Perirenal candidial abscess. AB - Perirenal candidial abscesses are rare, with few well-documented cases in the literature. We describe a case of a perinephric abscess treated with amphotericin B and nephrectomy. PMID- 2247925 TI - Methylene blue and pulse oximeter readings in a patient undergoing transurethral procedure. PMID- 2247926 TI - Femoral mononeuropathy after radical prostatectomy. AB - Femoral mononeuropathy is a recognized complication following abdominal and vaginal hysterectomy. Retractor injury and lithotomy position were postulated mechanisms. We report a femoral nerve lesion following a radical perineal prostatectomy. PMID- 2247927 TI - Indications for use of ketoconazole in management of metastatic prostate cancer. AB - Newer methods of androgen ablation for the treatment of metastatic prostatic carcinoma have been developed as alternatives to the standard forms of therapy, oral estrogens and surgical castration. The purpose of this review is to elucidate the indications and to determine the role of ketoconazole in the management of metastatic prostatic cancer. Eighteen patients have been treated with ketoconazole. The indications for usage have included: prompt therapeutic response, when orchiectomy is contraindicated, when estrogens are contraindicated, initial empirical therapy, and hormonally refractory disease. It can also be used in conjunction with luteinizing hormone-releasing hormone analogues. Ketoconazole is excellent for short-term usage prior to bilateral orchiectomy and when prompt therapeutic response is needed but orchiectomy cannot be performed. However, it is not particularly useful for long-term hormonal therapy. PMID- 2247928 TI - Simple technique for total ureteral stent control. PMID- 2247929 TI - Tetracyclines in urology: current concepts. AB - Tetracyclines have an unusually broad spectrum of antimicrobial activity. They are generally well tolerated, with relatively few side effects compared with alternative antibiotic choices. Tetracyclines also compare favorably with newer antimicrobials, i.e., oral quinolones, with respect to cost and microbial resistance. Doxycycline's and minocycline's spectrum of antibacterial activity, pharmacokinetic profile, and safety profile make them preferred drugs when tetracyclines are indicated in urologic infections. PMID- 2247930 TI - Testicular calcifications and neoplasia in patient treated for subfertility. AB - A subfertile male with a history of left cryptorchism underwent scrotal ultrasound that revealed stippled calcifications, without associated mass, in the right testicle. Six months later, while on a regimen of clomiphene citrate, a testicular tumor became palpable. This was sonographically confirmed to be surrounding the calcifications. Testicular calcifications are most commonly associated with benign conditions. We review the literature regarding their relationship to neoplasms and the significance of the ultrasonic findings. Furthermore, this is the sixth reported case of testicular tumor developing during hormonal treatment for oligospermia. Although these cases may be circumstantial, closer surveillance and screening ultrasound may be indicated for subfertile males taking clomiphene citrate. PMID- 2247931 TI - Hemorrhagic cystitis: failure of estrogen treatment. PMID- 2247932 TI - Comparison of rinderpest and peste des petits ruminants viruses using anti nucleoprotein monoclonal antibodies. AB - Monoclonal antibodies (MAbs) were obtained using a purified preparation of the RBOK strain of a rinderpest vaccine virus. The cytoplasmic immunofluorescent staining test showed that these clones had specificity for the nucleoprotein (N) of the virus. Six clones which immunoprecipitated the N protein corroborated these results. Thirteen anti-N MAbs were used to compare geographically widespread rinderpest viruses (RPV) and peste des petits ruminants viruses (PPRV) to two other morbilliviruses, measles (MV) and canine distemper (CDV). The N protein antigen profiles of the 23 isolates determined by immunofluorescent staining and enzyme linked immunosorbent assay (ELISA) on infected cells enabled us to classify the strains into groups. A differential identification of the morbilliviruses can be made using one MAb or associations of the MAbs. The potential to distinguish between RPV and PPRV and between virulent and avirulent strains of rinderpest is of primary interest. PMID- 2247933 TI - Detection and quantitation of a type D retrovirus gag protein in ovine pulmonary carcinoma (sheep pulmonary adenomatosis) by means of a competition radioimmunoassay. AB - A heterologous competition radioimmunoassay (RIA) which consisted of 125I-labeled langur retrovirus major gag protein and goat anti-squirrel monkey retrovirus serum was used to detect a type D retrovirus-associated antigen in tumor cell homogenates, lung fluid, and cell culture supernatant fluids of naturally occurring and experimentally-induced ovine pulmonary carcinoma (OPC, sheep pulmonary adenomatosis). In this assay, there was no cross reactivity between structural proteins of the type D retrovirus and an ovine lentivirus, which frequently co-infects OPC-affected sheep. The sensitivity of the assay was similar to an immunoblotting assay using antiserum to Mason-Pfizer monkey virus major gag protein which had been used previously to detect the OPC retrovirus antigen in tumor homogenates and lung fluids of OPC-affected sheep. All unconcentrated samples of lung fluid collected from five sheep with naturally occurring OPC or six sheep with experimentally induced OPC competed in the competition RIA. The competition RIA titers of the type D retrovirus antigen in lung fluids of lambs with induced OPC were relatively higher than the titers of this antigen in the naturally occurring OPC cases. The competition RIA detected the retrovirus antigen associated with OPC in the culture fluids of four out of five primary lung cultures from OPC sheep tested between 1 and 56 days after culture initiation. Because this RIA is appropriate for the quantitation of OPC associated antigen, it will provide a means for determination of the target cell type for OPC virus replication in vitro. PMID- 2247934 TI - DNA restriction endonuclease cleavage pattern and protein antigen profile of Ehrlichia risticii. AB - Molecular characterization of Ehrlichia risticii, the etiological agent of Potomac horse fever, was performed. Restriction endonuclease cleavage of E. risticii DNA generated distinct patterns by different enzymes. The DNA cleavage patterns of E. risticii isolates obtained from different geographic regions were similar. Protein analysis identified thirty-five distinct proteins with molecular weights ranging from 160 to 16 kilodalton (kDa). Antigenic analysis by radioimmunoprecipitation using 125I surface labeled E. risticii and by Western blotting determined the presence of eighteen antigens (160, 110, 86, 84, 81, 70, 55, 51, 49, 44, 41, 36, 33, 31, 28, 24, 22 and 16 kDa) of which nine (110, 86, 70, 55, 51, 49, 44, 33, and 28 kDa) were major antigens. Fourteen of these antigens, which included the major antigens, were apparent surface components. There were no heat-modifiable proteins but lipopolysaccharide components of 245 and 14 kDa, resistant to proteinase K and of non-antigenic character, were detected in the organism. PMID- 2247935 TI - A differential lysis method for the isolation of Cowdria ruminantium DNA. AB - In order to isolate pure Cowdria ruminantium DNA an enzymatic lysis procedure was used to lyse Cowdria-infected bovine endothelial cell cultures differentially. Infected host cells were treated with trypsin followed by DNase digestion and centrifugation. This method resulted in the isolation of intact Cowdria organisms and removed bovine DNA effectively. PMID- 2247936 TI - An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Anaplasma centrale and Anaplasma marginale. AB - An enzyme-linked immunoassay (ELISA) was applied to detect antibodies to A. centrale and A. marginale using homologous and heterologous antigens. The assay was compared with the indirect fluorescent antibody (IFA) test, and although a similar degree of sensitivity was obtained, the ELISA test had several advantages. Partially purified Anaplasma initial bodies used for antigen preparations contained negligible amounts of residual erythrocytic material, and did not interfere with the specificity of the ELISA. The antigenic similarity between A. marginale and A. centrale was further substantiated by cross reactivity obtained with heterologous antigens in both ELISA and IFA tests, and antibodies produced during natural infection with A. marginale were indistinguishable in both tests from those produced following vaccination with A. centrale. PMID- 2247937 TI - Phenotypical and genotypical characteristics of paired isolates of Pasteurella multocida from the lungs and kidneys of slaughtered pigs. AB - Twenty-eight strains of Pasteurella multocida were isolated from 12 Danish and two Canadian abattoir pigs. Fourteen strains were isolated from pulmonary inflammatory lesions, and 14 strains were isolated from kidneys of the same animals. Phenotypical and genotypical characteristics of the strains were evaluated with a view to determine if P. multocida isolated from kidneys might have been disseminated from the lungs. All field strains were capsular type A. The biochemical reactivity in the API-20E and API-ZYM commercial test-kits was uniform with the exception of alpha-glucosidase activity which was present at low levels in only ten of the strains. One strain was markedly serum sensitive, six strains slightly sensitive and the remaining were serum resistant. The peptide patterns obtained by polyacrylamide gel electrophoresis of whole cell proteins of the strains were very uniform with the exception of differences in intensity of bands in the 38 and 34 kD regions. The pattern of oligonucleotides obtained after electrophoresis of total genomic DNA digested with BamHI showed that the paired isolates had identical patterns in eight of the 14 animals. It is therefore likely that isolates from kidney lesions represent blood borne dissemination from primary pulmonary lesions. PMID- 2247938 TI - Development of an avidin-biotin dot enzyme-linked immunosorbent assay and its comparison with other serological tests for diagnosis of glanders in equines. AB - A dot enzyme-linked immunosorbent assay (dot ELISA) was developed for diagnosis of glanders in equines. The test was based on the detection of IgG antibodies to Pseudomonas mallei antigens bound to nitrocellulose coated on plastic strips (dipsticks), the reaction being amplified by an avidin-biotin system with biotinylated anti-horse IgG and horseradish peroxidase-avidin D. Sera from 810 normal, six naturally infected and 48 sensitized equines were tested by this assay, and results were compared with complement fixation, indirect haemagglutination and counter-immunoelectrophoresis tests. Dot ELISA had the highest sensitivity, and was superior to other tests in that it was rapid and easy to perform, the results were easy to interpret, the assay was not influenced by anti-complement activity, and it was able to detect antibodies at an early stage. Testing of serum at 1:200 dilution is proposed for epidemiological screening. PMID- 2247939 TI - Immunity to Chlamydia psittaci with particular reference to sheep. AB - Chlamydia psittaci, a zoonotic bacterium, is the causal agent of enzootic abortion of ewes, an important disease of sheep in many European countries. The major thrust of current chlamydial research is directed towards the human pathogen Chlamydia trachomatis. This review attempts to bring together relevant information concerning the host immune response to all members of the genus Chlamydiae and show how this has led to an increased understanding of the ovine humoral and cell mediated immune responses to C. psittaci while emphasising areas where there is still a lack of knowledge. Specifically the review looks at the common immuno-accessible antigens of the Chlamydiae and the antibody responses produced during infection, as well as covering the role of T cells and cytokines in the protective immune response. PMID- 2247940 TI - The treatment and prevention of bovine pneumonic pasteurellosis using antimicrobial drugs. PMID- 2247941 TI - Alterations in the systemic acid-base status and blood gas dynamics during progressive hypercalcaemia in calves. PMID- 2247942 TI - The immediate peripheral blood changes following chlorpromazine administration in aggressive mongrel dogs. PMID- 2247943 TI - The financial and production impacts of bovine dermatophilosis in Zambia. AB - During October to December 1986, 365 traditional cattle herds in four provinces in Zambia were inspected and the owners interviewed. Information was collected on the treatment, management and disposal of cases of bovine dermatophilosis and on the effects of this disease on productivity for 1985. The contemporary financial cost per case of treatment and/or premature disposal, slaughter or death to the owners was K. 202 (US$91). The cost due to draft oxen being affected was estimated at K. 428 (US$193) per affected ox. The cost of reduced milk production, replacing affected cows and calf deaths, directly or indirectly from bovine dermatophilosis, was estimated at K. 132 (US$78) per affected milking cow. The total annual national cost of bovine dermatophilosis in 1985 was conservatively estimated to be some K. 6.9 million, (US$3 million). There were indications that the true financial cost in 1985 may have been up to 1.8 times the estimated cost. PMID- 2247944 TI - The epidemiology of helminthosis in small ruminants under the traditional husbandry system in eastern Nigeria. AB - The epidemiology of helminth infections in West African dwarf sheep and goats under the traditional husbandry system prevailing in the derived savanna area of eastern Nigeria was studied for 12 months. The infections observed were due to Haemonchus contortus (87.1%), Trichostrongylus spp. (63.8%), metacestodes of Taenia hydatigena (30.2%), Oesophagostomum columbianum (22.4%), Strongyloides sp. (18.8%), Cooperia spp. (17.2%), Gaigeria pachyscelis (6.0%), Moniezia expansa (6.0%), Bunostomum trigonocephalum (4.3%), Trichuris ovis (3.5%), Capillaria sp. (0.9%) and paramphistomes (0.9%). Mixed infections were most prevalent. The endemicity of parasitic gastroenteritis in the area was indicated by the high prevalence of the helminths irrespective of the season of the year. The overall trend in helminthosis in these animals was that of an escalating worm burden during the period of confinement (April - October) and a low worm burden when animals were allowed free range (November - March), these periods corresponding to the cropping and harvest seasons respectively. A strong positive correlation (r = 0.73; p less than 0.01) was obtained between the mean strongyle worm burden and the eggs per gram (EPG) of faeces. A single treatment with a broad spectrum anthelmintic followed by movement into clean sheds at the beginning of confinement is suggested to give control of helminthosis in small ruminants in this area. PMID- 2247945 TI - Anaesthesia for fluorescein angiography of the ocular fundus in the miniature pig. AB - A safe and reproducible procedure is described for anaesthesia and ophthalmic fluorescein angiography in the miniature pig. Twenty examinations were performed in five adult miniature pigs. A detailed description is given of the anaesthetic procedure, in particular of the techniques for endotracheal intubation and for intra-arterial and intravenous cannulation. All cardiovascular parameters recorded during the experiments remained within acceptable anaesthetic limits. The fluorescein angiographic technique, which is routinely used in human ophthalmology, was adapted for the pig. This procedure for in vivo examination of the porcine eye is interesting and useful for experimental ophthalmic research. PMID- 2247946 TI - A comparison of some of the pharmacokinetic parameters of three commercial sulphadiazine/trimethoprim combined preparations given orally to pigs. AB - Three sulphadiazine/trimethoprim preparations were administered orally during feeding to pigs. Six male and six female pigs were used. Clinically important pharmacokinetic parameters of the two drugs in the three preparations were determined and compared. The plasma concentrations of sulphadiazine and trimethoprim increased rapidly in the pigs followed by a quite rapid decrease from 4 to 12 h after oral administration. The mean values of the absorption half lives of sulphadiazine and trimethoprim were 0.9-1.6 h and 0.5-0.8 h, respectively. The corresponding values for the elimination half-lives of sulphadiazine and trimethoprim were 3.1-4.3 h and 3.4-6.0 h, respectively. There were no significant differences between the pharmacokinetic parameters of the two compounds in the three preparations with the exception of Tmax for sulphadiazine and t 1/2 beta for trimethoprim. Comparative bioavailability calculations showed no statistically significant differences between sulphadiazine and trimethoprim in the three preparations. The weight increase of the pigs during the experimental period (mean = 37.3-64.9 kg) did not cause differences in the kinetics of the two drugs which could have consequences for the use of the three combined preparations in clinical practice. No unacceptable or antibacterial residues of sulphadiazine or trimethoprim were found in the kidneys of pigs slaughtered at 5, 7 and 10 days after administration. PMID- 2247947 TI - Efficacy of alpha-ketoglutaric acid as an effective antidote in cyanide poisoning in dogs. PMID- 2247948 TI - The serological response of young dogs to the Flury LEP strain of rabies virus vaccine. AB - The serological response of puppies from Nigeria to live Flury low egg passage (LEP) rabies vaccine was determined. Two sets of puppies were used: one set from rabies-vaccinated bitches and another set from non-vaccinated bitches. Puppies were vaccinated intramuscularly with Flury LEP strain rabies vaccine and serially bled from the 4th week to the 30th week. Serum rabies virus neutralizing antibodies (VNA) were measured by a modified rapid fluorescent focus inhibition test (RFFIT). Puppies from non-vaccinated bitches responded well to vaccination after the 4th week and through to the 10th week of age, showing a progressive increase in VNA. In contrast, puppies from vaccinated bitches responded well to rabies vaccination only at 10 weeks of age, although detectable maternal rabies VNA and rabies anti-ribonucleoprotein (RNP) antibodies had decreased by 6 weeks post partum. PMID- 2247949 TI - Changes of egg retinoids during the development of Xenopus laevis. AB - The changes of egg retinoids during the development of Xenopus laevis were investigated by high-performance liquid chromatography (HPLC). All-trans retinal and 3-dehydroretinal are endogenous in the egg and are distributed to both the eyes and the ventral portion of the larval body. These retinals are converted to all-trans retinyl palmitate and 3-dehydroretinyl palmitate during the development up to stage 46. 11-cis retinal and 3-dehydroretinal can be detected after stage 40 in the eyes but not in the larval ventral portion. It is suggested that retinoids are transported from the larval ventral portion to the eyes after stage 41/42. PMID- 2247950 TI - The effect of various anaesthetics on the spatial tuning of two major wave peaks in the transient pattern electroretinogram of the cat: evidence for pattern and luminance components. AB - The main PERG component of the transient contrast reversal pattern electroretinogram (PERG) in cats was a negative wave (3.5 microV average, SD 1.7 microV) peaking at about 130 msec (N130) with a spatial resolution above 5.5 c/deg, close to behavioural estimates. The early positivity (P35) was more variable, smaller and had lower spatial resolution. Different anaesthetic protocols affected both the waveform and the amplitude by spatial frequency functions. Responses of urethane anaesthetised cats were like those reported previously for decerebrate cats or cats paralysed and ventilated with N2O/O2/CO2 (75%/24%/1%). P35 was evoked only by coarse stimuli and N130 amplitude decreased linearly as spatial frequency increased. When the luminance response amplitude, predicted from the optical transfer function of the eye, was subtracted, spatial tuning appeared. An anaesthetic mixture of ketamine hydrochloride and xylazine depressed both P35 and N130 at low spatial frequencies while enhancing them at high frequencies. In paralysed animals ventilated with N2O/O2 (67%/33%) P35 was larger and recordable to 1.6 c/deg. Peak times were reduced and the inter-peak time halved. Other anaesthetics depressed the ERGs. These effects suggest that cats are a good model for studying N130 in isolation or its interaction with P35 and that both PERG peaks include luminance and pattern components. PMID- 2247951 TI - Binocular motion rivalry in macaque monkeys: eye dominance and tracking eye movements. AB - When the two eyes are exposed to markedly different patterns, perception becomes unstable, falling into oscillations, so that the image of one eye is seen first and then that from the other. With large stimuli the alternation is piecemeal, whilst when small stimuli are used the whole pattern alternates in unison. The purpose of this study was to determine whether a reliable, objective indicator of the perceptual state during binocular rivalry could be developed in the nonhuman primate. Monkeys (Macaca mulatta) were trained to discriminate direction of motion when presented with vertically drifting gratings moving in opposite directions in the two eyes. A high correlation was found between the direction of the slow phase of the optokinetic nystagmus (OKN) elicited by the drifting gratings during rivalry and the direction of motion reported by the monkey even though the gain of the OKN was reduced during rivalry, and the latency was longer. Behavioral eye dominance during rivalry varied significantly over time, between individuals and as a function of interocular contrast differences. Since the direction of tracking eye movements can be used to reliably monitor perceptual state during binocular motion rivalry, the opportunity exists in nonhuman primates to study the neurophysiological mechanisms underlying motion perception during the perceptually ambiguous condition of binocular rivalry. PMID- 2247952 TI - The use of different features by the matching process in short-range motion. AB - The perception of the direction of motion in luminance kinematograms breaks down when the displacement exceeds a few element widths (this limit is called Dmax). When kinematograms whose elements differ only, in hue are used, motion can be seen but performance declines at smaller displacements. The short-range process, once thought to be only a luminance correlator, is thus able to use hue. If the size of Dmax indicates how well a feature stimulates the motion sensors, hue might be said to have an especially weak input to motion sensors. In order to find the relative potency of luminance and hue as bases of the short-range matching process, Dmax for these features was compared to those obtained for kinematograms whose elements differed in phase (T-phase or L-phase) or orientation (/or/). The matching process could use all the features tested. Luminance seems to be the preferred basis for motion matching, with hue and phase (a tie) yielding smaller Dmax and orientation the smallest. PMID- 2247953 TI - Recognition of stimulus orientation. AB - The threshold for detecting a deviation in the orientation of a test stimulus from vertical and from horizontal was measured with a single test interval. The test stimuli were step edges, thin lines, and sine wave gratings of 2.5, 5.0 and 10.0 c/deg. Recognition thresholds were found to be independent of the frequency content and nature of the test stimulus. The average threshold value on the principal meridians was found to be approx. 0.6 deg. Additional testing was conducted with two interval forced choice designs, both with and without random perturbation of the orientation of the stimuli. Random perturbation of orientation reduces acuity estimates. The results are compared with those obtained by testing on the oblique meridia. We conclude that the meridional anisotropy of orientation discrimination, which favours the vertical and horizontal is a result, in part, of the influence of non-visual mechanisms. PMID- 2247954 TI - Assimilation and contrast in motion perception: explorations in cooperativity. AB - Motions within one region of the field influence motion seen elsewhere. To explore this phenomenon we used cinematograms comprised of alternating strips within which dots (i) tended to move in one direction, or (ii) moved in random directions (dynamic noise). When alternating strips were narrow, motion in one direction induced a similar direction of illusory motion in the adjoining dynamic noise (assimilation); when alternating strips were wide, motion tended to induce an illusory opposed motion in the dynamic noise (contrast). Since this illusory motion exhibits hysteresis, it probably results from spatially distributed, cooperative processes. The shift from assimilation to contrast, as the cinematogram's strips increase in size, suggests that facilitatory and inhibitory influences of the network extend over different distances. PMID- 2247955 TI - Detection of briefly flashed sine-gratings in dark-adapted vision. AB - Scotopic contrast sensitivity was measured near 20 deg retinal eccentricity for briefly flashed (10 or 20 msec) sine-wave gratings presented in darkness to dark adapted subjects. For very low spatial frequencies (0.2-0.5 c/deg), curves of contrast sensitivity vs luminous energy show evidence of a low rod plateau and a high scotopic region, with an intervening transition at around -2 to -2.5 log scot td sec. Similar measurements made using long flashed or flickering gratings do not show a plateau. The results suggest that vision in the low rod region is impaired for brief flashes. For the briefly flashed stimuli, curves of contrast sensitivity versus spatial frequency in the low region were best fit by simple Gaussian functions with a variable centre size (sigma c = 0.5----0.25 deg), size decreasing with increasing flash energy. Difference-of-Gaussian functions with constant centre size (sigma c = 0.25 deg) provided the best fit in the high region. Overt input from the cones and grating area artefacts are excluded by appropriate tests. Calculation of photon flux into the receptive field centres suggests that signal compression in P alpha ganglion cells contributes to the low rod plateau. PMID- 2247956 TI - The influence of spatial frequency on perceived temporal frequency and perceived speed. AB - Speed matching experiments were conducted using drifting gratings of different spatial frequencies in order to assess the influence of spatial frequency on perceived speed. It was found that gratings of high spatial frequency appear to drift more slowly than low spatial frequency gratings of the same actual velocity. The perceived temporal frequency of a counterphase grating similarly declines as spatial frequency increases. The previously reported effect of temporal frequency on perceived spatial frequency probably does not contribute to these phenomena. Our results suggest that the motion sensors thought to operate within different spatial frequency ranges have different velocity transfer functions, a fact not incorporated in existing computational models of motion perception. PMID- 2247957 TI - Development of contrast sensitivity in the human infant. AB - Contrast sensitivity and grating acuity were measured using the sweep VEP method in a group of 48 infants from 2 to 40 weeks of age and in a group of 10 adults. Sinusoidal gratings were reversed in contrast at 12 alternations per sec at a space-average luminance of 220 cd/m2. During 10 sec trials, either the contrast or the spatial frequency was increased in a series of 19 steps. Thresholds were estimated by extrapolation of the VEP response functions to zero amplitude. The contrast threshold at low spatial frequencies developed rapidly from 7% contrast at 2-3 weeks to an asymptote of 0.5% at 9 weeks. For adults, maximum sensitivity at low spatial frequencies was 0.32-0.22%. The sweep VEP estimate of grating acuity showed a gradual increase in spatial frequency with age, starting at 5 c/deg during the first month and reaching 16.3 c/deg at 8 months. The mean adult acuity was 31.9 c/deg. There appeared to be two phases in the development of contrast sensitivity and acuity. Between 4 and 9 weeks overall contrast sensitivity increased by a factor of 4-5 at all spatial frequencies. Beyond 9 weeks, contrast sensitivity at low spatial frequencies remained constant, while sensitivity increased systematically at higher spatial frequencies. PMID- 2247958 TI - Stereopsis, cyclotorsional "noise" and the apparent vertical. AB - In principle, stereopsis can be used to evaluate the subjective vertical in a sagittal plane, but temporal variation in cyclotorsion should degrade that ability. Video recordings of eye orientation during steady fixation were used to evaluate long-term instability in cyclotorsion. Torsion was measured simultaneously in each eye at 1-sec intervals during about 30 sequential fixations (5-sec duration) on the same target. For each eye separately, the standard deviation of torsion around its mean value averaged about 18 min arc. Some of this variation was conjugate, but the variability in torsional difference between the eyes averaged 17 min arc. Most of this second-to-second variation arose between fixations (average SD = 15 min arc). Such low-frequency, inter fixational variation in torsional difference between the eyes must produce spurious horizontal disparities in the upper and lower visual fields, and should thereby limit the precision with which the vertical horopter can be evaluated. All subjects exceeded those theoretical limits on precision, however, in performance tests requiring that two vertically separated targets be adjusted to apparent equidistance--but only when permitted to shift fixation back and forth between the upper and lower targets. That latter result provides a challenge to current understanding of stereopsis. PMID- 2247959 TI - Displacement thresholds for various types of movement: effect of spatial and temporal reference proximity. AB - Displacement thresholds for unidirectional stop-go-stop and continuous types of movement were measured as a function of duration of movement. A circular stationary reference of varying radius surrounding the stimulus was either present throughout the whole duration of movement, disappeared just before movement began, or was totally absent. In the absence of the reference, thresholds increased with duration according to a constant velocity prediction. When present continuously, thresholds for all durations of movement were reduced. For references of close proximity, displacement thresholds became independent of movement duration. Results are discussed in terms of direct mechanisms of movement detection and also spatio-temporal hyperacuity analysis mediating the detection of relative positional change. PMID- 2247960 TI - Post-receptoral undersampling in normal human peripheral vision. AB - In human far peripheral vision, drifting stimuli of particular periodicities appear to move in the opposite direction from their true direction of motion. This "reverse motion illusion" is a consequence of spatial undersampling of the retinal image. The illusion occurs for spatial frequencies an order of magnitude lower than that expected on the basis of anatomical measurements of human photoreceptor density. We conclude that for naturally imaged stimuli the site of undersampling in far peripheral vision must be post-receptoral. PMID- 2247961 TI - Blue light hazard in rat. AB - Rats have been extensively used in light damage studies. Retinal damage threshold for white light were found at 1-10 J/cm2, and the action spectrum resembled the absorption spectrum of visual pigment. We wished to answer the question whether a different class of light damage, the "blue light hazard", with white light damage thresholds at about 300 J/cm2, and an action spectrum peaking in the ultra violet, could also be demonstrated in rat. To that purpose 5 deg patches of retina were exposed to white xenon light with exposure times between 10 sec and 1 hr. We found that for funduscopic threshold damage the product of irradiance and exposure time was constant at a level of 315 J/cm2. Thereafter, the action spectrum was measured by exposing rat eyes to narrow band spectral lights. Threshold irradiant dose ranged from 4 J/cm2 at 379 nm to 2000 J/cm2 at 559 nm. Thus, susceptibility for damage sharply increased towards the ultra-violet, just like in earlier monkey studies. We conclude that in similar experimental conditions susceptibility to photic injury in rat is comparable to that in primates. Rat is the first species for which two different action spectra of photochemical damage have been established. PMID- 2247962 TI - Binocular vergence influences the assignment of stereo correspondences. AB - A modified version of the double-nail illusion was used to measure the influence of binocular vergence on stereoscopic matching. The method is more sensitive than previous procedures and allows quantitative results for various stimulus markers. The results show that matches in the fixation plane are strongly preferred over matches with high disparities. PMID- 2247963 TI - Comparison of vestibulo-ocular reflex (VOR) modification methods in cats. AB - The vestibulo-ocular reflex (VOR) has been measured and optically modified in several animal species. The VOR gain can be increased optokinetically by rotating the animal's visual surround opposite to the animal's direction of rotation or a VOR increase can result from the use of magnifying lenses. We describe here a comparison of three methods for producing VOR increases in cats: (i) optokinetic drum; (ii) a pair of 2.2 x telescopic lenses; (iii) Fresnel lens goggles. The animals were put through several preliminary calibrations followed by a sequence of VOR modification periods alternating with 10 testing periods. The results of the comparison in 4 cats show that the Fresnel lens system produces a greater and more stable VOR gain increase than the other two methods. PMID- 2247964 TI - [Left ventricular ejection fraction estimated by 2-dimensional echocardiography]. AB - Visual assessment of the reduction of left ventricular volumes during the cardiac cycle, which is the basis for calculation of the left ventricular ejection fraction followed up from several planes in real time is close to the objectively assessed changes estimated by various time consuming methods from two-dimensional echocardiography by the one- or two-plane method. The author's method makes it possible to assess the left ventricular ejection fraction and to divide it for clinical needs into four groups: normal above 60%, slightly reduced 45-60%, reduced 30-45% and markedly reduced 30% or less. The described echocardiographic examination method is invaluable when practiced by an experienced worker with restricted time for examination. PMID- 2247965 TI - [The effect of smoking on menopause]. AB - The authors investigated the age of onset of the menopause by random selection, using a questionnaire, in 344 women aged 43 to 90 years in relation to smoking. They evaluated 107 non-smokers, 112 passive smokers, and 118 active smokers. The mean age of onset of the menopause in non-smokers was 49.8 +/- 4.1, in passive smokers 49.1 +/- 4.9 and in active smokers 48.1 +/- 4.3 years. Active smokers had their menopause on average by 1.7 years sooner than non-smokers (p less than 0.01). This difference depended on the duration of smoking and increased with the number of smoked cigarettes to as much as 2.4 years in smokers of greater than 20 cigarettes per day and to three years when also the mother of the investigated woman was a smoker (p less than 0.01). PMID- 2247966 TI - [The prevalence of bronchial asthma in a selected sample of the adult Prague population]. AB - The authors assessed the prevalence of bronchial asthma in 8458 18-year-old and older inhabitants of an economic area in Prague 8. The population of the area up to December 31, 1987 was 90,458 adults. The health communities were selected in a random way to comprise the central as well as peripheral parts of Prague 8. By means of questionnaires information was assembled from 70.9% of the respondents and after supplementation of data by various doctors the scope of information was 89.9% (7605/8458). For detailed examination 902 subjects were selected with "confirmed" and suspect symptoms of asthma. The anamnestic data were analyzed and pulmonary ventilation was examined (flow-volume), and depending on indication, also the provocation or bronchodilatation inhalation test, skin tests, and total IgE. The cumulative prevalence of bronchial asthma was 2.3% +/- 0.3% (174/7605). The highest prevalence values were in subjects under 20 years--3.5% and under 30 years--3.6%. The contemporary prevalence was 2.0% +/- 0.3% (152/7605). Nonatopic asthma was recorded in 54%, atopic asthma in 46% of the subjects. PMID- 2247967 TI - [Development of disorders of glucose tolerance in the offspring of diabetic parents]. AB - The author investigated the development of abnormalities in the glucose tolerance in 70 subjects, 36 men and 34 women, where both parents were type II diabetics. The mean age of the offspring was 35.2 +/- 7.4 years, the mean follow up period 8.7 +/- 3.9 years. In the present work the blood glucose level and serum insulin after an oral glucose tolerance test are evaluated and compared with the results of tests of a matched control group of 37 healthy subjects without a family history of diabetes. Based on repeated examinations the group was divided into sub-groups: with a repeatedly normal glucose tolerance (38%) and sub-groups where at least once a borderline glucose tolerance was recorded (19%), or impaired glucose tolerance (24%) and diabetes (19%). These abnormalities developed variably and were associated with an increased and delayed insulin secretion. Insulin resistance developed. A significant difference was found in the blood glucose levels during the initial normal test among offspring with a repeatedly normal glucose tolerance and offspring who changed from normal glucose tolerance to impaired glucose tolerance and diabetes. From the prognostic aspect the blood glucose level two hours after glucose administration was most valuable. PMID- 2247968 TI - [Early diagnosis of nephropathy in type I diabetics]. AB - In 68 type I diabetics without permanent proteinuria, mean age 28 +/- 9 years, where diabetes was detected at the age of 14 +/- 7 years and persists for 14 +/- 8 years the urinary excretion of albumin and beta-2-microglobulin was assessed. The results were evaluated in relation to the persistence of diabetes, the blood pressure reading, family-history of diabetes and type of insulin therapy. In addition to microalbuminuria in 29% of the subjects which is a manifestation of glomerular damage, the authors detected in 58% elevated beta-2-microglobulin excretion indicating early changes of the proximal tubule. There was a relationship between microalbuminuria and "relative hypertension" which enhances albumin excretion and increases the risk of diabetic nephropathy. The relationship between microalbuminuria and a positive family-history of diabetes supports the hypothesis of a genetic background for the possible development of nephropathy. There was also a relationship with the duration of diabetes and the favourable effect of prolonged intensive insulin treatment. The clinical impact of beta-2-microglobulinuria in the diagnosis of the incipient stage of diabetic nephropathy must be tested in future investigations. PMID- 2247969 TI - [The ISIINR computer program for laboratory standardization of the prothrombin test]. AB - Expression of results by means of INR is a clinically important standardization of the prothrombin test. The INR values of healthy subjects are as a rule within the range of 1.0 and 1.2. Calibration of thromboplastin and processing of the results of the prothrombin test is facilitated by the computer programme ISIINR. PMID- 2247970 TI - [Familial incidence of diffuse idiopathic skeletal hyperostosis]. AB - The authors describe the incidence of diffuse idiopathic skeletal hyperostosis in three members of a family--father and two daughters. Some diagnostic problems of the disease are also discussed. PMID- 2247971 TI - [Transesophageal echocardiography--new possibilities of peroperative monitoring of cardiac hemodynamics]. AB - The authors describe a new method of monitoring of the heart during operation- Intraoperative transoesophageal echocardiography (TEE). They discuss the influence exerted on the cardiovascular system by anaesthesia and surgery and the possibility of echocardiography to record their consequences. The authors describe briefly the technique of this monitoring, possibilities how to evaluate the global and regional function of the left ventricle, the cardiac output, preload. They compare intraoperative transoesophageal echocardiography with invasive methods used for monitoring of cardiac function during operation. PMID- 2247972 TI - [Diabetic osteopathy. 5. Prevention]. AB - The author presents an account on possibilities of prevention of osteoporosis and osteomalacia in diabetics by eliminating or reducing some causes which lead to these complications. In osteoporosis this involves a modified diabetic diet, burdening of the bones by suitable exercise, compensation of diabetes and screening and treatment of complications of diabetes. Prevention of osteomalacia in diabetics includes according to the author adequate exposure to ultraviolet rays which ensures an adequate amount of vitamin D in the skin, dietary measures and administration of vitamin D, treatment of complications of diabetes and methods of mobilization of the patients. PMID- 2247973 TI - [Vitamin D and the immune system]. AB - The authors draw attention to the contemporary broad concept of the vitamin D endocrine system comprising in addition to the gut, bones and kidneys, some other tissues and cells incl. cells of the immune system. They give an account of findings on receptors for the active hormonal metabolite of vitamin D, 1,25 dihydroxycalciferol [1,25(OH)2D], in the cells of the immune system and summarized contemporary ideas on the mechanism of action of 1,25(OH)2D in these cells. They discuss the role of 1,25(OH)2D in non-specific and specific immune processes, and based on data from the literature and results of their own experimental work, they evaluate the possibility to apply the immunoregulating action of vitamin D in clinical practice. PMID- 2247974 TI - [Cor pulmonale and cor pulmonale decompensation--what is the future of these terms?]. AB - Decompensated cor pulmonale is a clinical syndrome manifested by signs of congestive heart failure in pulmonary disease. The authors emphasize that the haemodynamic characteristic of the syndrome differs substantially from the classical picture of chronic heart failure: the cardiac output is usually normal at rest and sometimes even during exercise, signs of impaired contractility of the right ventricle are absent and the effect of cardiac glycosides is minimal. It is possible that the clinical syndrome of decompensated cor pulmonale is caused mainly by respiratory failure and subsequent impaired function of some organs, in particular the kidney. PMID- 2247975 TI - [Use of nonparametric methods in medicine. II. Comparison of levels in 2 related samples]. AB - The authors present two non-parametric tests which are suitable for comparison of the level of a random variable on the basis of results obtained from two dependent samples. The sign test is discussed which is based on the evaluation of the statistical significance of the difference in the number of positive and negative deviations. The application of this test in practice is facilitated by the enclosed table which gives critical frequencies which still lead to the refusal of the zero hypothesis. The authors discuss also Wilcoxon's test for paired values. This test takes into account not only the trend of deviations but also their magnitude and thus uses more information than the sign test and has thus a greater scope. For this test an auxiliary table of critical values is also presented. PMID- 2247976 TI - [International Forum for the Evaluation of Cardiovascular Therapy--Lisbon, Portugal, March 3-6 1990]. PMID- 2247977 TI - [Balneology]. PMID- 2247978 TI - [Early history of the founding of the medical history chair at the University of Vienna (1833 to 1848/1850)]. AB - Regular lectures in the history of medicine were held after 1833 by Romeo (Roman) Seligmann (1808 to 1892). Only after 15 years of uninterrupted activities in the field he was appointed professor, and after another 2 years he was granted a salary. PMID- 2247979 TI - [Pictures of diseases]. AB - It very often happens that the general practitioner by his investigations draws near to the diagnosis of a disease but fails to reach the level of certainty. Then he has to confess reality by a correct denomination: it is a classification of the "picture of a disease". This way he demonstrates that he did not make an unshakable diagnosis. Making diagnoses does mean to have come to an end with the diagnostic work. Having classified a picture of a disease on the other hand stands for diagnostically "remaining in watchful expectancy". That situation usually is veiled by undue making use of the word diagnosis. PMID- 2247980 TI - [Correlation between late potentials, left ventricular function and coronary heart disease]. AB - By signal averaging it is possible to registrate late, fragmented low amplitude signals (late potentials, LP's) from the bodysurface 26 patients (21 males, 5 females) with a mean age of 57 years were investigated by signal averaging, Holter-monitoring and cardiac catheterization. 11 patients had a dilative cardiomyopathy (group A), 10 patients a coronary heart disease (group B), 5 of them with an ejection fraction greater than 50%, 5 of them with a reduced ejection fraction, whereas the control-group with 5 patients (group C) showed no coronary stenosis or reduced ventricular function, 6 out of 11 patients with dilative cardiomyopathy showed LP's; all of these with Lown IVb had LP's. In 2 patients with coronary heart disease and good left ventricular function late potentials were found, and in all 5 patients with disturbed left ventricular function. The control-group revealed no late potentials although 4 patients had Lown IVa or more in Holter-ECG. In conclusion, late potentials show a good correlation to malignant ventricular ectopic beats in patients with dilative cardiomyopathy and coronary heart disease, especially when the left ventricular function is reduced. PMID- 2247981 TI - Allergologic aspects of skin-cleansing products. AB - A review of the international literature and our patch test-results in 4637 patients with contact dermatitis and in 140 persons with a proven formaldehyde allergy revealed: Skin-cleansing products may contain a lot of ingredients which are known as allergens in single cases or-more accidentally - in limited epidemic outbreaks of contact dermatitis, but compared with the enormous amount of their worldwide application the incidence of allergic side-effects is low. They are much more important (in 14% of our patients with contact dermatitis) as an irritant co-factor for sensitization due to other allergens. PMID- 2247982 TI - Skin tolerance to cleansing agents. AB - The types of surfactants used for skin cleansing are discussed. Methods for the evaluation of the relative irritant potential of skin cleansers are reviewed. PMID- 2247983 TI - The effects of the detergent action of cleansing agents on the skin. AB - Detergent substances are important components of cleansing materials. Their detergent cleansing action may also result in skin toxicity. Methods for the evaluation of their toxic effect on the skin surface are reviewed stressing the usefulness of the soap chamber test, and newer in vitro cultural techniques. The action of detergents in promoting desquamation and removing intercorneocyte materials is also discussed. Finally, the point is made that cleansing can also be accomplished with non-detergent containing cleaners. PMID- 2247984 TI - Skin cleansing in dermatoses. AB - Following a swift survey of the different types of cleansers, the author focused the discussion on the management of chronically altered skin states, e.g. atopic dermatitis. Cleansing principles of such a condition primarily involves the prevention of any further local inflammation and stratum corneum dehydration in an attempt of pruritus and xerosis soothing effect. Cleansing rules in atopy are developed through recently demonstrated pathogenic features of this condition. PMID- 2247985 TI - Cleansing problems in senile skin. PMID- 2247986 TI - Children's skin and cleansing agents. AB - Due to its particular physiology, baby skin is highly sensitive towards cleansing agents especially during the child's first period of life. Dermatologists therefore suggest cleansing rules and recommend the use of suitable products to avoid skin defects by cleansing agents. PMID- 2247987 TI - Cleansing of hair and scalp in health and disease. AB - Shampoos contain tensioactives, densifying agents, preservatives, chelating agents, colour, perfume, water and additives. Synthetic anionic tensioactives were the most used. Cationic and amphoteric are also useful. Shampoos could incorporate additives to correct certain functional defects. A good prescription and choice is convenient to have the desired benefit and avoid hair alteration. PMID- 2247988 TI - Skin cleansing of the mucous membrane and skin borders. PMID- 2247989 TI - Skin cleansing in health and disease. AB - Skin cleansing has to be considered as an important component of daily hygiene in normal skin and as an important part of therapy in diseased skin. The crucial point is the choice of the cleansing agent to be recommended as skin tolerance of detergents is sometimes low. The evaluation of cleansing products depends upon their cleansing action (detergent or adsorptive), on the general and specifically epidermal toxicity of the components, on the rinsability of the product, and on the amount and nature of the additives, e. g. perfume oils. The knowledge of all the above-mentioned points will help the cosmetic adviser as well as the dermatologist to make the right choice depending upon the actual condition of the skin. PMID- 2247990 TI - [Experiences from general practice: use of acetylsalicylic acid and anticoagulants in patients following acute myocardial infarct]. AB - An effective therapy with coumarin derivatives within the secondary prevention after acute myocardial infarction makes great demands on the dispensary care. The risk of serious complications is relatively high. The risk of therapy with acetyl salicylic acid (ASS) in low dosage is significantly smaller. A significant decrease of the rate of reinfarctions and lethality by acetyl salicylic acid was made evident. The retrospective evaluation of the duration of treatment and effectiveness of the therapy with anticoagulants in postinfarction patients (n = 260) had the following result: reduction of the anticoagulant therapy from 75% in the year 1985 to 35% in the year 1989. Increase of the acetyl salicylic acid therapy (250 mg/day) from 23% to 60% in the same period. Up to 1987 the average duration of treatment with anticoagulants was 61.2 +/- 33.6 months, since 1988 only 9.6 +/- 2.6 months. 80% of the patients had a temporary ineffective therapy with anticoagulants, 50% were transitorily in the therapeutic risk region. At present only patients with an increased thromboembolic risk received an obligatory anticoagulant therapy. PMID- 2247991 TI - [Multiple reuse of disposable material for insulin injection without resterilization]. AB - Of 123 type I diabetics 306 one-way syringes and canules, respectively, were repeatedly used for the insulin injection in the domestic milieu (altogether 4,157 injections). The average duration of application was 29 days (2-296), the average number of injections 51 (4-422). Of 81% of the patients no immediate cleaning was made. No local reactions appeared at the sites of injection. At the end of the use all injection materials were free from bacterial contaminations (determination of the germ number in the lumen of the syringes and canules). One way material can repeatedly be used by one and the same diabetic for the insulin injection in the domestic milieu, observing a normal personal hygiene regimen (1 week or 30 injection in uninterrupted sequence). It is not necessary to perform an intermediate cleaning of the materials. PMID- 2247992 TI - [Quality control of blood glucose self-monitoring using the Glucosignal test strip and Haemo-Glucotest 20-800]. AB - In 157 capillary blood samples of type I diabetics parallel determinations of the blood sugar concentration were performed by means of the visual evaluation of the test strips Glucosignal and Haemo-Glucotest 20-800 in comparison to an enzymatic reference method by trained special personnel. On the basis of the correlation coefficients the two test strips showed a good accordance between visual evaluation and the reference method (r = 0.98 and 0.97, respectively). In comparison to the reference method in Glucosignal there is a tendency to underestimation (-0.67 mmol/l), on the other hand in the Haemo-Glucotest 20-800 the blood glucose concentrations are on an average +0.87 mmol/l above the reference value. In visual valuation of the blood glucose concentrations by means of Haemo-Glucotest 20-800 with increasing blood glucose concentration an increasing inexactness is to be stated, whereas Glucosignal is characterized by more favourable parameters of quality. PMID- 2247993 TI - [Selected psychoneurotic-somatic disorders and diseases of the digestive tract. An integrated unitary concept]. AB - On the occasion of the 10th anniversary of the inauguration of our new, modern Department of Internal Medicine in Jena it is our intention to characterize, at least roughly, the contribution to its profile that has been made since its institutionalization. In this context, problems that were related to the main tasks in patient care and to the character of the division of general internal medicine had to be picked out from the multitude of services which have been provided by the staff of the division for the benefit of our citizens. As exemplified by two problematic syndromes of the digestive tract, we wished to demonstrate that a non-integrative dualistic medical practice in diagnostics and therapy is not suitable to produce the necessary qualitative breakthrough in our public health service. Only by stepwise and limited diagnostics can a balanced cost-to-benefit ratio be advocated for the patient and the society. Our scientifically oriented mode of prescribing therapeutic measures for the citizens in our public health institutions is intended to harmonize, more than ever before, quality with economics, as the international trend of growing costs in public health services also holds true for the GDR. These few suggestions will have outlined at least first steps in the right direction. PMID- 2247994 TI - [Medicine and natural sciences in the Dessau cultural district of the 18th century. On the 250th anniversary of the birth of Leopold Friedrich Franz (1740 1817) of Anhalt-Dessau]. AB - The 250th anniversary of the birthday of Prince Leopold Friedrich Franz of Anhalt Dessau gives occasion to the appreciation of the progressive achievements of this representative of an enlightened absolutism, taking into particular consideration medicine and natural sciences. Under his reign a public health was established which was exemplarily organized by Dessau community physicians, the benefit of which the whole population of the country enjoyed. PMID- 2247995 TI - [Guidelines for the treatment of hypercholesterolemia]. AB - The prevalence of mild and moderate hypercholesterolemia among the middle-aged population of the G.D.R. is about 30%. Thus, this is the most important risk factor for coronary heart diseases. Primary therapeutic techniques are elimination of overweight, low-fat diet, rich in monoenic and polyenic acids, and increase of physical activity. When by these measures a decrease of cholesterol to 5.2-5.5 mmol/l is not achieved the introduction of lipid drugs is to be considered in dependence on the individual risk (associated risk factors like smoking, hypertension, diabetes, low HDL-cholesterol). In case of mild to moderate polygenic hypercholesterolemia cholestyramine, nicotinic acid and modern fibrates have the priority. Familial hypercholesterolemia demands as a rule the introduction of statins (e.g. lovastatin) or combinations of the above mentioned lipid drugs or the combination of cholestyramine and lovastatin, resp. In this way the prognosis even of patients with severe familial hypercholesterolemia can be improved decisively. Considering the fact that this would be a life accompanying therapy a thorough consideration of the risk/benefit ratio and an adequate medical supervision are necessary. PMID- 2247996 TI - [Experiences with conversion from MC-insulin NOVO to L-insulin S.N.C. of insulin dependent diabetic patients]. AB - After a circa 10-year therapy with MC-insulin NOVO 12 diabetics were changed to the chromatographically purified insulins L-insulin S.N.C. and insulin S.N.C. of the nationally-owned enterprise Berlin-Chemie. 3 and 6 months, respectively, ago after the ambulatory change the patients were metabolically, immunologically, hormonally and clinically characterized. Profiles of blood glucose, value of glycaemia and HbA1 also lipid parameters, creatinine values, residual B-cell function, blood pressure and ophthalmologic state did not show any significant differences to the initial values after change to S.N.C.-insulins. Insulin antibody level (9.5%-9.4%-9.7%) and insulin need (0.48 IU/kg-0.46 IU/kg-0.48 Iu/kg) also remained unchanged. Local reactions were not observed. Under the condition of a permanently good quality of the S.N.C.-insulins (purity and stability of the preparations) the application of chromatographically purified insulin of the firm Berlin-Chemie with comparable therapeutic success as in insulin MC NOVO is possible in a large part of the patients. PMID- 2247997 TI - [Bilateral pleural mesothelioma--case report]. AB - It is reported on the rare case of a 46-year-old female patient with a bilateral mesothelioma of the pleura without contact to asbest. Although the female was suspected in a malignant tumor and many diagnostic investigations were performed, diagnosis could be ensured morphologically only a short time before her death. Causes and development of mesothelioma, histological types, clinical symptoms and diagnostic procedures are described. PMID- 2247998 TI - [Lipoprotein-cell interactions in relation to the risk of atherosclerosis]. PMID- 2247999 TI - [LDL receptor determination in mononuclear blood cells]. AB - The determination of the LDL-receptor-activity with 125I-LDL according to Goldstein and Brown is regarded as reference method, because it permits the quantitative measuring of the partial receptor functions binding, internalization and degradation of LDL. The authors inform of their experiences with the assaying of the LDL-degradation in mononuclear blood cells (lymphocytes and monocytes). The most critical step of the method is the radioactive labelling of the LDL. The quality criteria of the labelling are discussed. The results of the receptor activity assays from patients with heterozygous familial hypercholesterolemia demonstrate that it is necessary to assay patients and normal persons for each 125I-LDL-lot and to calculate the data of the patients in relation to the normal persons because of the limited standardization of the method. In the clinical medicine, today the receptor assay is only indicated for the genetic counseling of patients which are suffering possibly from familial hypercholesterolemia. PMID- 2248000 TI - [Characterization of enzyme immunoassays for T4 determination]. AB - We compared an enzyme immunoassay for T4 (MTPT4) developed in Halle with the Enzymun-Test T4, Boehringer Mannheim (BMT4). Calculated coefficients of correlation can not be used for interpretation of the two methods. By construction of Bias-profiles the evaluation of concentration depended precision and accuracy is possible. Both methods can be used equally in laboratory work. PMID- 2248001 TI - [The validity of sodium excretion in urine in normotensives and hypertensives in a selected population]. AB - Salt intake of 503 people from the south western area of the GDR was investigated. Salt intake is high (151 mmol/d), but lower then expected. There are no important differences between people without (140 mmol/d) and with (161 mmol/d) a essential hypertension. Salt intake of male is higher than female persons. There is no correlation between the height of salt intake and the elevation of systolic or diastolic blood pressure. PMID- 2248002 TI - [Enzyme variation after a special diet in spontaneously hypertensive rats (SHR)]. PMID- 2248003 TI - Multiple representations of the body and input-output relationships in the agranular and granular cortex of the chronic awake guinea pig. AB - The organization of somatosensory input and the input-output relationships in regions of the agranular frontal cortex (AGr) and granular parietal cortex (Gr) were examined in the chronic awake guinea pig, using the combined technique of single-unit recording and intracortical microstimulation (ICMS). AGr, which was cytoarchitectonically subdivided into medial (AGrm) and lateral (AGrl) parts, also can be characterized on a functional basis. AGrl contains the head, forelimb, and most hindlimb representations; only a small number of hindlimb neurons are confined in AGrm. Different distributions of submodalities exist in AGr and Gr: AGr receives predominantly deep input (with the exception of the vibrissa region, which receives cutaneous input), whereas neurons of Gr respond almost exclusively to cutaneous input. The cutaneous or deep receptive field (RF) of each neuron was determined by natural peripheral stimulation. All studied neurons were activated by small RFs, with the exception of lip, nose, pinna, and limb units of lateral Gr (Grl), for which the RFs were larger. Microelectrode mapping experiments revealed the existence of three spatially separate, incomplete body maps in which somatosensory and motor representations overlap. One body map, with limbs medially and head rostrolaterally, is contained in AGr. A second map, comparable to the first somatosensory cortex (SI) of other mammals, is found in Gr, with hindlimb, trunk, forelimb, and head representations in an orderly mediolateral sequence. An unresponsive zone separates the head area from the forelimb region. A third map, with the forelimb rostrally and the hindlimb caudally, lies adjacent and lateral to the SI head area. This limb representation, which is characterized by an upright and small size compared to that found in SI, can be considered to be part of the second somatosensory cortex (SII). A distinct head representation was not recognized as properly belonging to SII, but the evidence that neurons of the SI head region respond to stimulation of large RFs located in lips, nose, and pinna leads us to hypothesize that the SII face area overlaps that of SI to some extent, or, alternatively, that the two areas strictly contiguous and the limits are ambiguous, making them difficult to distinguish. The input-output relationships were based on the results of RF mapping and ICMS in the same electrode penetration. The intrinsic specific interconnections of cortical neurons whose afferent input and motor output is related to identical body regions show a considerable degree of refinement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2248005 TI - Reaction times for hand movements made in response to visual versus vibratory cues. AB - Reaction times were determined for monkeys and humans who made wrist flexion and extension movements in response to vibratory and visual cues. Humans initiated movements approximately 50 msec sooner in response to vibratory as compared to visual cues. For monkeys, this difference was approximately 100 msec. Mean daily reaction times for monkeys and humans improved with practice until they reached a steady level of performance. Increased differences between vibratory and visual reaction times were weakly correlated with increased age of humans. The increase in the differences appeared to result from decreased reaction times by older subjects for vibratory-cued movements; reaction times for visually cued movements did not consistently vary across the age range of subjects tested (19-36 years). The results obtained using this novel paradigm suggest that it may be a useful tool for simultaneously testing behavioral performance or neurological function during somatosensorimotor and visuomotor tasks. PMID- 2248004 TI - Areal distributions of cortical neurons projecting to different levels of the caudal brain stem and spinal cord in rats. AB - Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Agm), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb. The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2248006 TI - [Prevention of early postoperative hematoma with the use of elastic bandages. Its ultrasonic diagnosis and control]. AB - The authors stress out the importance of an application of elastic bandage for a prevention of the early postoperative hemathomas in traumatized patients, whose effect can be controlled by ultrasound. 58 patients were elaborated, of whom in 30 cases an elastic bandage was placed at the end of surgery, and 28 patients (control group) without dressing. In 8 patients of the control group, an existence of postoperative hemathomas was proved by ultrasound, while only in two cases with postoperative bandage a presence of such hemathoma could be discovered. Lesser number of postoperative hemathomas in patients with elastic bandage is statistically important (p less than 0.001). Obtained results indisputably point out the value of elastic bandage application in the course of first three postoperative days in traumatized patients. PMID- 2248007 TI - [Tennis elbow]. AB - The article describes disease known as tennis elbow. Possible causes and morphologous substrate is mentioned. Diagnostics are described briefly. Conservative and operative measures are included. The simplest operative treatment is described. Possible causes of failures in operative treatment are discussed in every case. Analysis of 19 patients treated on surgical Dept. of General Hospital in Novo mesto in the years 1972-1987 is added including possible explanation of four unsuccessfully treated cases. PMID- 2248008 TI - [Testing of an intramedullary reinforcement in osteosynthesis bridging of bone defects using methylmethacrylate]. AB - The purpose of this testing was to determine whether the routinely used intramedullary metallic plate can be replaced by our newly constructed metallic reinforcement ladder without interfering with the static properties of the bone alignment. Our results showed that the alignment obtained by the application of the new metallic reinforcement had the same static value as the formerly used technique. The new technique is superior to the former one as concerns the bending loads due to the greater distance between the external osteosynthesis plate and the reinforcement, and because of the greater friction between the reinforcement and methyl-methacrylate than between the metallic plate and methyl methacrylate. PMID- 2248009 TI - [A complex injury of the knee joint associated with a popliteal artery lesion- case report]. AB - Injuries of the popliteal artery are frequent in the dislocations of the knee joint, and an early diagnosis of a lesion of the popliteal artery is the base for the successful treatment. Generally, in all the traumas in the region or proximity of the knee joint, it should always be taken into consideration a possibility of arterial injury. In our case there was a posterior knee joint luxation with evidently contused and thrombosed popliteal artery. The surgery was done in an inappropriate time (more than 14 hours after the injury), and consisted in a Goretex graft interposition, and following a ligamentary reconstruction a transitory arthrodesis with external fixator (AO) in one level was carried out, what can be a model for similar situations. A control arteriography immediately before the patient's discharge from the hospital showed an arterial passage, while clinically an evidently lesser posterior unstability existed. In the surgical managing of such injuries it is necessary an interdisciplinary approach, appropriate period of time and corresponding sequences of repairs. PMID- 2248010 TI - [The Collis-Nissen operation in the treatment of reflux due to esophageal stenoses associated with brachioesophagus]. AB - Eight patients with esophageal reflux strictures and brachioesophagus were treated by endoscopic dilatation and the Collis-Nissen procedure between 1986 and 1990 at the Institute of Digestive Diseases, Belgrade University Clinical Center. Dilatation of the esophageal stricture was performed by the Eder-Puestow system. All strictures were dilated preoperatively to in average 45 Fr without any complications recorded. The average duration of the Collis-Nissen operation was 3.5 hours and it was hastened by the usage of GIA surgical stapler for construction of the Collis gastroplasty tube. Postoperative course was uneventrful in all eight patients and by dismissal all of them had satisfactory relief of dysphagia and barium esophagogram. Postoperative hospital stay averaged 13.0 days. Satisfactory symptomatic control of gastroesophageal reflux (no symptoms, no treatment) was achieved in 5 patients at a long-term follow-up. Two patients required periodic dilatations and antireflux therapy during the first postoperative year to achieve resolution of the dysphagia and no need for medical therapy. One patient had objective failure of reflux control and progression of stricture formation requiring reoperation. This patient underwent esophagectomy and esophagocoloplasty with a subsequent good result. The combined Collis gastroplasty-Nissen funduplication has become the operation of choice in patients with dilatable reflux stricture and esophageal shortening and a reasonable alternative to a formidable resectional procedures. This report evaluates the first experiences with a Collis-Nissen procedure in our country. PMID- 2248011 TI - [The effect of the age of the child at the time of surgery for pectus excavatum on respiratory function and anthropometric parameters of the thorax]. AB - Respiratory function and anthropometric parameters of the chest were studied in two groups of children aged 15, undergoing pectus excavatum repair before and after the age of 12, respectively. Mean values of static and dynamic functional respiratory parameters were significantly lower in children operated before the age of 12. Sagital diameters of the chest determined at the level of sternal angle and costal arch intersection were significantly shorter in children operated before the age of 12. Restricted respiratory motility of the chest and shorter sagital diameters are very likely caused by the damage of active ossification centers in the sternum of children. The results support the indications for pectus excavatum repair beyond the age of 12. PMID- 2248012 TI - [Morgagni's diaphragmatic hernia--case report]. AB - A sucostosternal hernia (type Morgagni) is a rare diaphragmatic anomaly of congenital origin; in that sense are data that from 100 operated on diaphragmatic hernias, only three belong to this type. Although it is known that 20% of patients with congenital diaphragmatic hernia have other congenital anomalies, a coincidence of a Morgagni's hernia with heart anomalies, in available to use (domestic and foreign) references, there has not yet been reported. Besides a Morgagni's hernia, our patient also had an insufficiency of mitral and tricuspidal valves, atrium septum defect (sec.), pulmonary hypertension and Hiss' right branch block. Surgery was successful: the diaphragmatic defect (size: 7 cm. x 3 cm.) repaired, and the complex heart anomalies corrected in an extracorporeal circulation. PMID- 2248013 TI - [Relaparotomy for intra-abdominal hemorrhage]. AB - On 36,536 abdominal operations, in 36 patients (0.1%) there was necessary to perform a relaparotomy due to intraabdominal hemorrhage, of whom in 28 patients this complication arised after emergency surgical interventions, while in 8 cases after elective surgery. The cause of bleeding in 26 patients were technical mistakes during the first intervention, in two the overdosage of anticoagulants, in other two a fibrinolysis, and in one patient haemophilia. In 5 patients the origin of the hemorrhage could not be verified at relaparotomy. Clinical picture of an intraabdominal bleeding depended on its acuity and extent; in 18 patients the massive bleeding manifested suddenly or by progressive development of heart failure. In 7 patients slow evolution of the blood loss manifested with anemia and intestinal paresis. Hemoperitoneum arised in 6 patients, but without anemia, and in the other five remaining patients, a circuscripted intraabdominal hematoma was formed. In 8 patients laparocentesis was diagnostically successful. (The re laparotomy was lifesaving for 26 patients). 12 patients died. The authors believe that well knowning of parameters of central hemodynamics, together with prolonged paresis of the gut, hyperthermia and hyperleucocytosis it is possible to recognize the predominant signs of acute postoperative hemorrhage. PMID- 2248014 TI - [Duodenal obstruction caused by gallstones (Bouveret syndrome)]. AB - Gallstone obstruction of the duodenum (Bouveret's syndrome) is a very rare complication of biliary calculosis. A great biliary calculus with long-term persistence causes cholecystoduodenal fistula and after passing through this fistula into duodenum, subsequent duodenal obstruction develops. The authors present a 73-years-old woman with Bouveret's syndrome. She was admitted to the Institute of digestive diseases with clinical signs of high intestinal obstruction. Preoperative radiographic examination detected gallstone obturation of the duodenum. At operation, two large gallstones were extracted from the duodenum, a thickened gallbladder was removed and duodenal suture was done. Post operative course was delayed, due to respiratory complications and the patient went home on the 37th day after the operation in good condition. PMID- 2248015 TI - [Emergency surgical procedures in neonates and infants over a 20-year period]. AB - The authors analyse their experience concerning emergency treatments during the twenty year period at their Surgical department in which there never was a pediatric surgeon. The most common surgical procedures are presented, which should be carried out in emergency; it is accentuated that such patients have also to be surgically treated in Subregional hospital's Centers, in which there are no the necessary conditions; that does oblige the general surgeon to pay attention in his everyday activities to these small but delicate patients. Newborns and breastfed babies together with acute surgical disorders, can often have other health problems (or associated diseases), so that there is a necessity of team work and close collaboration between surgeon, anesthesiologist, pediatrician and radiologist in the managing of such patients. PMID- 2248016 TI - [Diagnostic and therapeutic significance of percutaneous nephrostomy in children]. AB - During the period from April 1986 to March 1988 on the Pediatric Clinic in Belgrade a total of 12 percutaneous nephrotomies were performed to relieve obstruction of the upper urinary tract. The youngest patient was a two-month old with giant hydronephrosis, and the oldest was a 12-year old girl with an acute kidney obstruction caused by impaction of wedging the poured off stone. The most common reasons for obstruction of the upper urinary tract were congenital stenoses and postoperative scars, urethrocystoneostomia and pyeloplasty. The most frequent clinical manifestations in patients on whom nephrotomy was carried out as an emergency operation were infection, palpable tumor (cyst) and acute kidney insufficiency. Percutaneous nephrostomy was always performed with basal sedation and local infiltrative anesthesia under X-ray control. Surgery was necessary in all cases, but no complications needing surgical intervention occurred. Mild hematuria can be expected at almost every punction, so it should not be treated as a complication. Dislocation of the nephrostoma catheter immediately after surgery can be a complication which necessitates reintervention, but if this happens after more than ten days, the catheter can easily be replaced through the formed fistulous channel. In one case percutaneous placing of the catheter was not possible, so it was placed surgically in the kidney and skin to enable drainage of the infected urinome a month after rupture of the ureteropyelic segment. Percutaneous placing of a catheter through the nephrostoma is the method of choice for urgent and temporary relief of obstructions of the upper urinary system regardless of etiology, and this procedure achieves immediate therapeutic and, if necessary, diagnostic effect which enables recovery of the patient and preparation for definitive surgery which in such a situation could be hazardous. PMID- 2248017 TI - A significant increase in stroke volume should be adequate to attenuate decreases in blood pressure during the establishment of epidural anesthesia in parturients. PMID- 2248018 TI - Environmental and occupational hazards of the anesthesia workplace. AB - Our present state of research and knowledge strongly suggests that the volatile agents, halothane, enflurane and isoflurane, present only a minimal threat to our environment. Nitrous oxide, however, has ozone-depleting potential as well as a greenhouse gas effect which may contribute much to the problem of global warming over the next few decades. Release of anesthetic gases into the atmosphere presents a small problem in contrast to other sources of ozone-depleting chemicals and greenhouse gases, but anesthesia providers have a responsibility to minimize unnecessary atmospheric pollution by reevaluating the use of N2O, using low flows of gases and exploring the use of activated charcoal absorption in the scavenging systems to remove volatile agents. Infectious waste, radiation, lasers, chemicals and waste gases pose possible occupational health hazards in the operating room. Each of us should play a critical role in monitoring harmful substances and should actively practice techniques which would lessen the hazards. We should be cognizant of the fact that sources not yet introduced into our environment may have adverse effects on our health and that vigilance and education are key factors in maintaining a safe work environment. PMID- 2248019 TI - Anesthesia Advantage, Inc. vs. Metz. PMID- 2248020 TI - Percutaneous transtracheal jet ventilation: an important airway adjunct. AB - Situations wherein patients cannot be ventilated or intubated rarely occur. When they do, however, death is imminent unless rapid and accurate actions are taken to restore adequate gas exchange. Under these circumstances, percutaneous transtracheal high-pressure jet ventilation (TTJV) through an intravenous catheter is life saving. The authors report two recent cases where TTJV was employed to regain control over obstructed upper airways. Discussion of the cases and the therapeutic modality follows. The summary includes a call for the immediate availability of TTJV at all anesthetizing locations. PMID- 2248021 TI - AANA Journal course. 10. AANA Journal course: new technologies in anesthesia: update for nurse anesthetists--integrating computer capabilities into the clinical setting. AB - Clinicians routinely use computer-integrated anesthesia equipment. Clinical application of computers is widespread and, with rapidly advancing computer technology, the availability of computer-integrated equipment is likely to expand. By being able to identify the general functional components of the computer and understanding some of the basics about how a computer functions, the clinician will be better prepared to decide which types of monitors and computer integrated technologies will most appropriately fit individual needs. PMID- 2248022 TI - Report of the National Commission on Nurse Anesthesia Education. PMID- 2248023 TI - [The inflammatory process]. AB - Foremost among the various mechanisms which have developed during the evolution of living creatures are those taking place during the inflammatory process, triggering defense mechanisms vs. chemical, physical and biological toxic agents. The present review aims at explaining some of the physiopathological mechanisms which play a role during inflammation. PMID- 2248024 TI - [Anti-inflammatory drugs in ORL]. AB - The idea of anti-inflammatory therapy in medicine arose in the 1950's with the development of corticosteroids. Prior to this time the treatment of phlogistic pathologies was aimed at achieving analgesic, antipyretic and diaphoretic effects. Cortisone and its derivatives have spurred the setting up of a series of pharmacological tests to study their anti-inflammatory activity and to verify their clinical efficacy in rheumatology. The side effects of corticosteroids have promoted research into non steroid anti-inflammatory drugs (NADs). A new pharmacological class has been created which includes substances-some previously known and some newly synthesized-which can also be used in disease other than rheumatic pathologies. In the E.N.T. field, both cortisone (and its derivatives) and NADs have been applied in many different types of inflammatory pathologies: infective and non infective, acute, subacute, recurrent, chronic and chronic with exacerbations. Modern antiphlogistic therapy avails itself of other therapeutic means of defense as well; means such as proteolytic and secretolytic enzymes, antiedematous substances and the old sulphuric crenotherapy whose action mechanism can, today, be newly interpreted and reassessed in light of modern pharmacological knowledge. PMID- 2248025 TI - [Pharmacological and clinical profile of tiaprofenic acid]. AB - Tiaprofenic acid is a new generation anti-inflammatory drug synthesized to be a valid alternative to both cortisone preparations and other NSADs since it is less toxic yet equally effective. Its anti-inflammatory, analgesic, antipyretic activity is due to a particular interference mechanism active in the early phases of the inflammatory process (PG synthesis inhibition, stabilization of lysosomal membranes). Thanks to its good trophism toward tissues in the otolaryngological area and its tolerability this drug would appear particularly suited for the treatment of inflammatory E.N.T. pathologies. PMID- 2248026 TI - [Tiaprofenic acid: levels in plasma and upper airway tissues]. AB - Inflammatory processes of the upper airways can be successfully improved by using non steroid anti-inflammatory drugs, alone or in association with antibiotics. Recent clinical reports suggest that tiaprofenic acid (TA) is particularly suited for this purpose. This fact can be explained on the basis of the drug's pharmacokinetics and by the high concentration TA can achieve in the respiratory tract mucous membranes. In order to confirm this hypothesis TA levels were studied in the plasma as well as in tonsillar and turbinal tissue. Patients admitted for tonsillectomy or turbinectomy were given two tablets (600 mg) of TA from one and a half to five hours before surgery. In all cases blood and tissue samples were taken at the same time during surgery and drug levels determined by HPLC. Plasma levels ranged from 12 to 26 to 32.2 microgram/ml; tissue levels ranged from 3.9 to 5.4 to 4.9 micrograms/g, respectively, depending on time of administration. There was no significant difference between tonsillar and turbinal tissue. These results suggest a good penetration of nasal and airway mucosa by TA and are in agreement with the clinical data on the efficacy of TA in dealing with upper airway inflammatory conditions. PMID- 2248027 TI - [Anti-inflammatory agents in ORL diseases. Introduction]. PMID- 2248028 TI - [Action of an anti-inflammatory agent on the nasal mucosa]. AB - The histological integrity of the nasal mucosa assures full efficacy of the respiratory, conditioning and defense functions. Together with ciliated and goblet cells, the respiratory epithelium not only carries out mucociliary clearance but it is also responsible for correct assembly of secretory IgA, the foundation of the mucosal defense system. The secretory component stabilizing the immunoglobulin molecule is indeed, an epithelial glycoprotein which begins to fail when the mucous trophism is altered through inflammatory processes of various natures. The efficacy of an anti-inflammatory drug (tiaprofenic acid) can thus be proven not only because the respiratory and mucociliary transport functions are normalized but, histologically speaking, through an accumulation of IgA in the epithelial cells and nasal secretions as well. In the present experiment the effect of tiaprofenic acid on the local production of antibodies appears prompt and long lasting. On the contrary, respiratory function and mucocillary transport are more deeply affected by structural alterations of the epithelium, most likely because the histological integrity-demonstrated by the increase of IgA in the secretion and accumulation of the secretory component in the epithelium-is the starting point for a perfect coordination according to fixed biological rhythms of all nasal functions. PMID- 2248029 TI - [Effects of tiaprofenic acid on nasal mucociliary transport time]. AB - Mucociliary activity is a fundamental aspect of the clearance function of the respiratory tract; mucociliary transport time being the easiest parameter to record in regard to the overall, more complex function of nasal clearance. A double blind, multicenter randomized study was carried out on 40 rhinopathy patients divided into two groups and treated with tiaprofenic acid 300 mg or a placebo twice a day for seven consecutive days. Before and after treatment the following were recorded: subjective and objective nasal MCT time, using an original composition of vegetable charcoal powder and saccharin powder at 3%; nasal obstruction. The authors conclude that the treatment of rhinitis with tiaprofenic acid improved not only the clinical symptomatology but also the mucociliary transport time and rhinomanometric examination. PMID- 2248030 TI - [Tiaprofenic acid: a clinical study of 1186 patients with inflammatory ORL diseases]. AB - A multicenter trial is presented involving 39 Italian university and hospital centers and 1186 patients (mean age 37.6 +/- 0.46 years) suffering from phlogistic aural (33.7%), rhino-sinusal (22.5%) or pharyngolaryngeal (43.8%) pathology. These patients were treated with 600 mg of tiaprofenic acid daily for a period of 7 days. The drug was administered either as monotherapy (53.2% of the cases) or in association with antibiotics (46.8%). Tiaprofenic acid showed similar therapeutic efficacy under both conditions, carrying out a clear antipyretic, anti-inflammatory, mainly analgesic action in the pathologies of all three otolaryngological areas. Treatment tolerance and compliance proved quite good. Only 20% of the patients claimed light side effects. The treatment was interrupted only in 18 (1.5%) of the 1186 patients studied. PMID- 2248031 TI - [Efficacy and tolerance of tiaprofenic acid in acute inflammatory ORL diseases: a multicenter study of 4231 patients]. AB - In order to evaluate effectiveness and safety of tiaprofenic acid (TA), a multicenter study involving outpatients followed by ENT specialists was carried out. Since October 1988, the trials have prospectively enrolled 4231 patients. The demography of the study's population was: 2165 male and 2066 female, mean age 39.6 +/- 15.8 years. The patients were divided into the following groups by pathology: 1281 (30.4%) otitis, 654 (15.5%) rhinosinusitis, 2178 (51.6%) pharyngo laryngo-tonsillitis, and 112 (2.6%) flue syndrome, 300 mg b.i.d. of TA was orally administered for seven consecutive days. At T0 and T7 parameters ranged from 75 90% for symptoms related to inflammation of the oral tract, 80% for nasal edema and 100% for otalgia. The physician's judgement about the drug's effectiveness was 90.6% excellent or good. Side effects were reported in 409 cases (9.6%) mainly related to the gastrointestinal tract. There were 72 drop-out (1.7%): 38 (0.9%) for drug intolerance. In conclusion, TA showed excellent safety and effectiveness in improving the recovery of ENT's outpatients. PMID- 2248032 TI - How do dogs determine the direction of tracks? AB - Two professional tracking dogs were brought in at right angles to 50-m-long tracks to try to identify the clues that the dogs used to determine the direction of the tracks. When the dogs were tested on tracks laid by a walking man, they took the direction that the track-maker had moved significantly more often than predicted by random choice regardless of whether the person had moved forwards or backwards. When tested on tracks laid by bicycling on grass or asphalt, the choice of direction was not significantly different from random, even though the dogs were always rewarded when making correct choices. When four leather strips were tied to the back tyre of the bicycle before laying the track, the one dog tested took the correct direction significantly more often than predicted by random choice. When the leather strips were smeared with sausage before laying the tracks, the dog took the wrong direction more often than predicted by random choice. However, when rewarded for making correct choices, the dog learned to choose the direction in which the bicycle had actually moved. We suggest that our dogs determined the direction of tracks by comparing the scents of consecutive prints and following the prints in the direction of increasing intensity. PMID- 2248033 TI - Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperaemia in skeletal muscle and their underlying regulatory mechanisms. AB - The reactive hyperaemia response cat skeletal muscle to 2-120 s arterial occlusions was analysed with regard to amplitude, duration, 'excess blood flow' and site of dilator action along the vascular bed. The last-mentioned was assessed with a new whole-organ technique permitting continuous segmental resistance recordings in arterial vessels greater than 25 microns, arterioles less than 25 microns and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles less than 25 microns in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels greater than 25 microns and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium-derived relaxing factor) did not seem to affect the reactive hyperaemia response. PMID- 2248034 TI - Effects of magnesium on isolated human fetal and maternal uteroplacental vessels. AB - The effects of Mg2+ were studied in human umbilical arteries, stem villous arteries and maternal intramyometrial arteries. The vessels were dissected and mounted in organ baths, and isometric tension was recorded. In all fetal preparations investigated, Mg2+ (0.5-6.0 mM) in a concentration-related way decreased pD2 values for prostaglandin F2 alpha responses. The maximum response to prostaglandin F2 alpha was depressed in umbilical arteries, but remained unaffected in stem villous artery preparations. In stem villous arteries pretreated in Ca2(+)-free medium, increasing concentrations of Mg2+ markedly depressed the response to Ca2+ after stimulation with K+ or prostaglandin F2 alpha, suggesting that Mg2+ inhibited transmembrane calcium influx and interfered with intracellular calcium effects. In both stem villous and intramyometrial arteries, increasing concentrations of Mg2+ increased EC50 values for responses to K+, whereas Emax values were unaffected. Mg2+ produced relaxation of agonist induced contractions by up to 60% in stem villous arteries and up to 40% in intramyometrial artery preparations. The relaxant effect of Mg2+ did not seem to be mediated through the endothelium or through changes in the synthesis of prostanoids, since endothelial disruption and treatment with indomethacin left the responses to Mg2+ unaffected. Relaxation of vessels important for resistance regulation in the human uteroplacental vascular bed may be of benefit when uteroplacental blood flow is impaired, and the present results support the established use of magnesium sulphate in the treatment of pre-eclampsia. PMID- 2248035 TI - Influence of serotonin on total intravascular capacity in the anaesthetized dog. AB - The influence of serotonin on intravascular volume in the total capacitance circulation has not previously been examined. Thus, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that total intravascular volume changes could be recorded as the inverse of changes in reservoir volume in 31 anaesthetized dogs. Serotonin (588 +/- 47 micrograms) in the left atrium was associated with an initial decrease in intravascular volume of 39 +/- 12 ml (P less than 0.01) followed by an increase of 129 +/- 31 ml (P less than 0.01) above control at 20 min. Mean arterial pressure increased from a control of 74 +/- 4 mmHg to 99 +/- 7 mmHg (P less than 0.01) initially and then decreased to 64 +/- 5 mmHg (P less than 0.05) at 20 min. Following ganglionic blockade with mecamylamine, serotonin caused only a decrease in intravascular volume, which was 73 +/- 12 ml (P less than 0.01) at 20 min. 5 HT2 and alpha-adrenergic blockade with ketanserin did not attenuate the early decrease in intravascular volume. 5-Carboxamidotryptamine (82 +/- 39 micrograms), a 5-HT1 agonist, was associated with only an increase in intravascular volume, which was 82 +/- 13 ml (P less than 0.01) at 20 min and which was abolished after ganglionic blockade. Thus, serotonin causes a biphasic change in total intravascular volume. The initial decrease in intravascular volume is not mediated by a reflex or by 5-HT1, 5-HT2, or alpha-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248036 TI - Influence of angiotensin on total intravascular capacity in the anaesthetized pig. AB - The present study examined the influence of angiotensin on total intravascular capacity. In eight anaesthetized pigs, splenectomy, carotid sinus denervation and cervical vagotomy were performed. Blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be recorded as the inverse of changes in reservoir volume. Angiotensin administration at 0.2 microgram kg-1 min 1 i.v. for 5 min was associated with a decrease in total intravascular volume of 57 +/- 6 ml (P less than 0.05) and an increase in aortic pressure from 96 +/- 5 to 119 +/- 6 mmHg (P less than 0.05). With subsequent angiotensin administration in five of the animals, the responses were not attenuated. In five of the animals, angiotensin was associated with a decrease in intravascular volume of 72 +/- 8 ml (P less than 0.05) before abdominal evisceration and 33 +/- 13 ml (P less than 0.05) after evisceration. These responses were significantly different from each other. In four of these eviscerated animals, angiotensin was associated with a decrease in intravascular volume of 35 +/- 17 ml (P less than 0.05) before ligation of all four limbs and a decrease of 36 +/- 4 ml (P less than 0.05) after limb ligation. Thus, angiotensin acts directly to decrease total intravascular volume. The decrease is due to decreases in both splanchnic and extrasplanchnic volume. The extrasplanchnic volume decrement is not due to decreases in skeletal muscle or cutaneous tissue intravascular capacity in the limbs. PMID- 2248037 TI - Inotropic mechanisms of amrinone in papillary muscles from guinea-pig hearts. AB - Isometric force and action potentials were recorded in papillary muscles from guinea-pigs (temperature 33 degrees C, stimulation frequency 0.5 Hz). Amrinone (1 mM) increased peak twitch force (to 220% of control, n = 12) and rate of rise of force (to 221% of control, n = 12), while time from peak to half-relaxation was markedly reduced (to 70% of control). The time to peak force was not significantly changed. Action potential at 50% repolarization was shortened (93.3% of control, n = 8), whereas plateau voltage became more positive. Peak twitch force in response to a test stimulus after a varied interval, i.e. mechanical restitution, was increased at all intervals by the drug. However, the time to full mechanical restitution (1.5 s) was not affected. Forces in response to the test interval preceding the previous contraction (post-extrasystolic potentiation) were analysed. Maximum potentiation was 16.0 mN mm-2 (2.7 +/- 0.4%) before and 22.6 mN mm-2 (1.7 +/- 0.1%) after addition of the drug, i.e., the relative potentiation was diminished in the presence of the drug. The test interval for optimum potentiation was shortened from 370 to 320 ms (P less than 0.05, n = 12) in 1 mM amrinone. During decay of post-extrasystolic potentiation peak force of the post-potentiated contraction was linearly related to force of the potentiated contraction. The slope of this line (which is believed to monitor recirculation of activator calcium) was increased by amrinone from 0.37 to 0.50 (P less than 0.01, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248038 TI - Effects of indole-pyruvic acid on sleep and food intake in the rat. AB - Indole-pyruvic acid was studied for its short- and long-term effects on electroencephalographic sleep and on food intake in rats implanted with cortical and muscular electrodes. Following a single injection, indole-pyruvic acid (10-50 mg kg-1 i.p.) reduced by 16-23 min (range) the latency of the first slow-wave episode in a dose-related fashion and produced a significant increase in slow wave sleep time (12-40%) in doses of 10-30 mg kg-1. Rapid eye movement sleep latency and rapid eye movement sleep time were increased (by 23-37 min) and reduced (57-71%) respectively. The effects of indole-pyruvic acid on slow-wave sleep time were still present after 3, 7 and 14 days of chronic administration (10 mg kg-1 day-1), whereas tolerance to the effect of indole-pyruvic acid on rapid eye movement sleep was observed. Daily food consumption was reduced (20 28%) by acute administration of indole-pyruvic acid (15-30 mg kg-1 i.p.), but tolerance developed after 5 days of repeated injections. These findings are in accordance with previous evidence suggesting that indole-pyruvic acid effects may be related to the activation of central serotonin neurons, which are involved in the inhibitory control of sleep and food intake. PMID- 2248039 TI - Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3- secretion in the pig. AB - Secretin causes the bile duct cells to secrete HCO3-. To examine whether the transformation of duct cell ultrastructure that follows secretin stimulation depends on microtubules and is important for ductular HCO3- secretion, we examined the effect of colchicine on ductular HCO3- secretion and on the morphology of cells lining bile ductules of anaesthetized pigs. Colchicine blocked secretin-dependent cytoplasmic clearance of tubulovesicles and prevented expansion of the basolateral plasma membrane in duct cells and reduced the ductular HCO3- secretory response from 132 +/- 25 mumol min-1 to 97 +/- 14 mumol min-1. In contrast, lumicolchicine did not affect secretin-dependent tubulovesicle clearance or plasma membrane geometry or ductular HCO3- secretion. Accordingly, secretin-dependent cytoplasmic clearance of tubulovesicles in bile duct cells appears to depend on microtubules and to be important for ductular HCO3- secretion. PMID- 2248040 TI - Increased vasopressor potency of the centrally injected neuropeptide Y fragment 13-36 in the adult spontaneously hypertensive awake male rat of the Wistar-Kyoto strain. PMID- 2248041 TI - Partial curarization abolishes splitting of the inorganic phosphate peak in 31P NMR spectroscopy during intense forearm exercise in man. PMID- 2248042 TI - In-vivo stimulatory effects of mammalian gonadotropin-releasing hormone in male frog, Rana esculenta, during the post-reproductive period. PMID- 2248043 TI - Schizophrenia and assaultive behaviour: the role of alcohol and drug abuse. AB - To assess the role of alcohol and drug abuse among schizophrenics with assaultive behaviour, we analysed case records of 38 patients who were responsible for a total of 71 violent offences between 1972 and 1986. They were identified from a population-based cohort of 644 individuals with schizophrenia hospitalized in Stockholm County during 1971. Fourteen of the 38 offenders abused alcohol and/or drugs and another 7 were probable abusers. These figures are higher than previously reported as regards abuse among schizophrenics. Most of the offences were performed by nonhospitalized patients who had been ill for many years. The nature of most of the violent incidents resembled that of offences committed by non-psychotic individuals. Our findings give further evidence for the role of abuse and social disintegration in assaultive behaviour among persons with schizophrenia. PMID- 2248044 TI - The impact of phenotypic variation on genetic analysis: application to X-linkage in manic-depressive illness. AB - Genetic linkage studies have opened new vistas for behavioral and psychiatric genetics. However, phenotypic diversity and diagnostic uncertainties can lead to spurious linkage findings. A method of analysis is proposed that takes these factors into account. When applied to manic-depressive disease, the results indicate that previous evidence for a major gene localized on the distal long arm of the X-chromosome cannot be ascribed to phenotypic uncertainties and misclassifications, i.e., a type I error. Although the lod score (the logarithm of odds) favoring linkage is reduced with the more restrictive clinical definitions of the phenotype, it remains significant nonetheless. Thus, the linkage finding is robust over a range of phenotypic patterns and presumed phenocopy frequencies. The results also suggest that the X-linked phenotype is a particularly severe form of manic depression characterized by early onset, high familial prevalence of the bipolar form, and high recurrence rate of major depression. These findings may have important implications for the design and interpretation of genetic linkage studies and for refining diagnostic techniques in mental disorders. PMID- 2248045 TI - The phenomenology of psychiatric hospitalization: the patient's experience and expectations. AB - Patients admitted to a psychiatric hospital are confronted by complex and, at times, conflicting models and theories about the cause and treatment of their illness. The patient's understanding and experience of this process are analyzed in this phenomenological study. The need for patients' increased understanding of the purpose and functions of hospitalization is underlined as well as the possible discrepancy between the patients' and the hospital's perspectives on treatment objectives. PMID- 2248046 TI - Psychosexual development of adolescent males after malignancies in childhood. AB - We studied psychosexual development in 28 adolescent males who had survived leukemia and compared it with that in 25 adolescent males who had survived other malignancies in childhood. A clinical semistructured psychiatric interview was used to form 8 criteria of psychosexual development. Sexual identity was also assessed using a psychological test. By every criterion, development was more disturbed in patients who had survived leukemia. Attitudes toward adult-type genital sexuality, contact ability with the opposite sex, and the developmental level of sexuality were most significantly affected. PMID- 2248047 TI - Parental rearing behaviour, family atmosphere and adult depression: a pilot study with psychiatric inpatients. AB - In a sample of 72 depressed inpatients the relationships between severity of depression, emotional family atmosphere and perceived parental rearing were studied at admission, discharge and follow-up. The results indicate that paternal rejection and overprotection might be of particular importance for developing social skills used to form close relationships, whereas maternal emotional warmth seems to have a preventive effect by promoting emotional stability. PMID- 2248048 TI - Mortality in heroin addiction: impact of methadone treatment. AB - The mortality within a cohort of 115 street heroin addicts was studied for 5-8 years using the Kaplan-Meier survival estimate technique. This differed markedly from the relatively low mortality of 166 comparable heroin addicts given methadone maintenance treatment (MT). The street addicts' mortality rate was 63 times that expected, compared with official statistics for a group of this age and sex distribution. When 53 patients in MT were involuntarily expelled from treatment, due to violation of programme rules, they returned to the high mortality of street addicts (55 times that expected). A group of 34 rehabilitated patients who left MT with medical consent retained the low mortality of MT patients (their mortality rate was 4 times that expected). Despite this great improvement in survival, even patients in MT showed a moderately elevated mortality (8 times that expected), mainly due to diseases acquired before entering the treatment programme. It is concluded that MT exerts a major improvement in the survival of heroin addicts. PMID- 2248049 TI - Childhood vulnerability and adult invincibility. AB - This study is salutogenic, focusing on the people who cope successfully with the handicapping background of a high-risk childhood. Of those aged 0-15 in 1947 in a total population survey of 2 Swedish parishes, 221 persons with 3 or more childhood psychiatric risk factors were identified. Personal interviews were conducted with 148 of them in 1988-1989. Four measures were used: the Sense of Coherence Scale, the Symptom Distress Checklist, the Quality of Life Scale, and a qualitative overall measure of health status using all interview material. Data analysis focuses on stressing the considerable proportion who managed to overcome their handicapped backgrounds. The sense of coherence is proposed as a powerful explanatory variable in such success. PMID- 2248050 TI - Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study. AB - The authors compared 16 nondepressed obsessive-compulsive patients (OCS) with 8 normal controls (NC) of similar age for resting-state regional cerebral glucose metabolic rates (rCMRglu) using positron emission tomography with the fluorodeoxyglucose method. OCS were rated for clinical data, and a neuropsychological battery was administered to 14 patients on the day of the scan. Absolute rCMRglu for whole cortex, and normalized prefrontal lateral cortex metabolic rates, were both significantly lower in OCS than in NC. No significant difference between treated (n = 10) and drug-free (n = 6) OCS was found for those variables. OCS were significantly impaired in the neuropsychological tasks assessing memory and attention. The rCMRglu for prefrontal lateral cortex were negatively correlated to Stroop-test subscores. This "frontal-oriented" task assessed the ability of OCS to inhibit immediate but inappropriate responses. These results suggest, in OCS, a modification of the general activating systems of cortical function and a relationship between the lateral prefrontal rCMRglu decrease and a selective attention deficit. PMID- 2248051 TI - Relationship between expressed emotion and family burden in psychotic disorders: an exploratory study. AB - This study explored the relationship between level of expressed emotion (EE) and level of family burden in 20 families of individuals with psychotic disorder. Results indicated that a relationship between EE and family burden did exist, but it appeared to be strongly influenced by demographic and illness-related variables. The usefulness of the 5-min speech sample method of assessing EE was limited by the aversion of some family members to being videotaped and by denial of patient symptoms by some relatives. Other methodological weaknesses are discussed. The relationship between demographic and illness-related variables and level of EE needs further exploration. PMID- 2248052 TI - An American view of the ICD-10 personality disorders. AB - The 1986 version of the ICD-10 diagnostic criteria for the personality disorders was analyzed. In one part of the study, clinicians in the United States were asked to assign the ICD-10 criteria to the ICD-10 categories. In a second part, the ICD-10 criteria were assigned to DSM-III-R categories. In the first part, the face validities of the ICD-10 criteria were highly variable. Thirty percent of the criteria were assigned to the correct parent category by over 80% of the clinicians. In contrast, 34% of the criteria failed to be correctly assigned by at least half of the clinicians. Concerning the correspondence between ICD-10 and DSM-III-R categories, only anankastic (ICD) and obsessive-compulsive (DSM) showed a high level of correspondence. The correspondences of anxious (ICD) with avoidant (DSM), impulsive (ICD) with borderline (DSM), and histronic (ICD) with histrionic (DSM) were poor. PMID- 2248053 TI - Women as victims of torture. AB - This is a retrospective study on the effects of torture on Latin American refugee women in Toronto. Thirty-six cases of female torture victims are reviewed. The cases are divided in 2 groups, according to whether they experienced physical and psychological torture or only psychological assaults. Both groups are compared in terms of demographic characteristics, social and/or political involvement prior to the traumatic experiences, symptoms for which they sought psychiatric intervention and recovery rates. The symptoms presented by all women are consistent with those described in the literature for torture victims, regardless of their sex. The main findings are that women who experienced direct physical and psychological violence more frequently had persistence of symptoms than women who experienced only psychological violence. PMID- 2248054 TI - An investigation of dementia among elderly outpatients. AB - A total of 110 unselected demented outpatients aged 60 and over (mean age: 76.2 years), 69 women and 41 men, were prospectively investigated. A potentially reversible cause of dementia was found in 26 patients (normal pressure hydrocephalus 2, cerebral tumor 1, hyperthyroidism 2, hypothyroidism 4, vitamin B12 deficiency 13, pseudodementia 4). Follow-up investigation showed that the only true reversible dementia in which improvement from abnormal to normal mental status occurred and was sustained for up to 2 years was 1 case of normal pressure hydrocephalus and 1 case of pseudodementia. In all cases of vitamin B12 deficiency, hypothyroidism and hyperthyroidism, despite proper treatment, mental status did not improve significantly and follow-up in most cases showed persistant cognitive deterioration. It can be concluded that although true reversible dementias do exist, they do not seem as prevalent as previously reported. Most elderly outpatients with reversible causes of dementia do not revert to normal and continue showing progressive decline. PMID- 2248055 TI - Ventricular enlargement in normal weight bulimia. AB - Cranial computed tomography (CT) scans of 17 patients with bulimia were compared with those of 21 age- and sex-matched controls. The ventricular brain ratio (VBR) of the bulimics was 7.29, which was significantly greater than the 4.55 seen in controls. However, no correlation was found between VBRs and clinical variables, endocrine or metabolic parameters. PMID- 2248056 TI - Gait disorders in tardive dyskinesia. PMID- 2248057 TI - Use of reversible inhibitors of monamine oxidase-A in major depression and other psychiatric disorders. Proceedings of a symposium. Athens, Greece, 13-19 October 1989. PMID- 2248058 TI - Comparison of monoamine oxidase-A inhibition by moclobemide in vitro and ex vivo in rats. AB - Inhibition of MAO activity was measured in rat brain homogenates using 5-HT as MAO-A substrate and phenylethylamine as MAO-B substrate. Moclobemide rather selectively inhibited MAO-A. Its inhibitory potency is rather low, like that of toloxatone, whereas clorgyline, harmaline, cimoxatone and brofaromine were all found to be at least 100 times more potent. Phenelzine, isocarboxazid and tranylcypromine were nonspecific, inhibiting MAO-A and MAO-B to about the same extent. The same drugs were also tested ex vivo. Here again moclobemide preferentially inhibited MAO-A; it was equipotent to clorgyline and brofaromine in these tests, and 2-4 times as potent as cimoxatone and harmaline. Moclobemide is a relatively weak MAO-A inhibitor in vitro and yet more potent in vivo than other reversible inhibitors, suggesting that the compound may be converted in vivo to an active form. Nevertheless, it has not been possible so far to identify activated derivatives, and recent findings that moclobemide markedly inhibits liver MAO-A within 5 min of an intravenous injection strongly suggests that the compound itself is responsible for the inhibition. PMID- 2248059 TI - Short-lasting and reversible inhibition of monoamine oxidase-A by moclobemide. AB - In ex vivo experiments, the time course of monoamine oxidase-A (MAO-A) inhibition after 10 mg/kg oral moclobemide was virtually the same for whole rat brains and liver: the onset was rapid, the maximum effect was obtained in 15 min, and the duration of action was short (about 16 h) compared with several days for the irreversible MAO inhibitors. The time course of MAO-B inhibition was peculiar: almost complete inhibition was obtained in the time only between the first and second hours, whereas in the whole brain, or various brain areas, maximum MAO-B inhibition (40%) did not occur until 2 h after drug administration. Inhibition in other peripheral organs, such as kidney and small intestine, was of even shorter duration (3 h). After even marked MAO-A inhibition in the liver by moclobemide, the activity recovered within about 4 h when the homogenate was dialysed against water or buffer at 37 degrees C. This rapid recovery is temperature-dependent and does not occur at 18 degrees C. The substance causing the marked inhibition of MAO-A activity when moclobemide is given is probably itself inactivated by the enzyme (reversibility by metabolism). It is expected that more insight into the mechanism of action of moclobemide will be obtained from the use of highly purified preparations of the MAO-A isoenzyme. PMID- 2248060 TI - Hypotensive action and weak potentiation of tyramine effect by moclobemide in rats. AB - Moclobemide belongs to a new class of reversible, selective monoamine oxidase-A (MAO-A) inhibitors; it is clinically well tolerated and has little liability to potentiate tyramine pressor effects. Measurement of blood pressure and heart rate in conscious, freely moving rats showed only a slight, nonsignificant decrease in mean arterial pressure in normotensive animals. However, in spontaneously hypertensive rats, moclobemide significantly decreased blood pressure by 20 mmHg within 30 min of oral intake of 30 mg/kg. In the same animals, heart rate was decreased by 20%; normal values returned after 2-3 h. Tyramine alone in oral doses up to 15 mg/kg had no effect on blood pressure in normotensive rats, and after treatment with 30 mg/kg moclobemide, tyramine at 5 mg/kg did not alter mean arterial pressure, whereas there was a significant increase after doses of tranylcypromine, toloxatone and brofaromine. Higher doses of tyramine (10-20 mg/kg) following moclobemide led to a rise of 30-40 mmHg in pressure, but this had disappeared within 20 min. This effect was almost completely eliminated by desipramine, suggesting that coadministration of a norepinephrine uptake inhibitor with a reversible MAO inhibitor is likely to reduce the risk of tyramine-induced hypertensive crisis. Thus, the authors conclude that moclobemide exerts only a slight hypotensive action in hypertensive rats, and differs from other MAO inhibitors in potentiating the pressor effect of tyramine only weakly. PMID- 2248061 TI - Species-specific biotransformation of moclobemide: a comparative study in rats and humans. AB - This study measured plasma concentration of moclobemide and 2 of its active metabolites in the rat after oral doses of 30 mg/kg moclobemide. The secondary amine metabolite Ro 16-3177 was found in rat plasma at all times investigated (up to 3 weeks); the peak concentration of 200 ng/ml was reached 15 min after administration of moclobemide. The primary amine 16-6491 was found after only 30 min at about 40 ng/ml, and remained at about one half to one third the level of the secondary amine. Unchanged moclobemide appeared in much higher concentrations than the metabolites initially, but declined rapidly to about the same level as Ro 16-3177 by 3 h. In the humans, peak concentrations of moclobemide were reached more slowly than in the rats, and neither of the amine metabolites was found in human plasma at any time. Metabolism of moclobemide, as has been shown for other morpholine compounds, is quantitatively different in rats and humans. Since the concentration of Ro 16-6491 in human plasma remains below the limit of detection, only a very weak inhibition of MAO-B is produced in human platelets, and moclobemide can thus be considered a selective MAO-A inhibitor in humans. PMID- 2248062 TI - Antidepressants, alcohol and psychomotor performance. AB - The acute psychomotor effects of moclobemide, a reversible inhibitor of MAO-A antidepressant (100 and 300 mg) compared with amitriptyline (25 and 75 mg) showed that moclobemide caused no significant impairment in contrast with amitriptyline, which caused significant impairment at both doses. Two other studies are reviewed. One study reported the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg), placebo, and alcohol (0.5 g/kg) or placebo in an elderly group: moclobemide caused little impairment or alcohol potentiation and may reverse some alcohol impairment, whereas trazodone caused substantial impairment and alcohol potentiation. Another study of the acute and chronic effects of moclobemide (200 mg 3 times daily) or clomipramine (25 mg twice daily) and their interactions with alcohol (blood alcohol concentration 0.6 g/l) showed that alcohol caused significant impairment, whereas clomipramine tended to enhance and moclobemide to reduce some impairment. Moclobemide appears to be an antidepressant with few psychomotor effects and minimal alcohol potentiation and may reduce some alcohol impairment. PMID- 2248063 TI - Efficacy of reversible inhibitors of monoamine oxidase-A in various forms of depression. AB - The design and the main therapeutic results of 3 controlled double-blind studies comparing moclobemide with tricyclics and/or placebo in depressed patients are presented. Moclobemide, a reversible inhibitor of monoamine oxidase (RIMA), preferentially inhibits MAO-A. It showed good efficacy in major depression (DSM III), both endogenous and non-endogenous. The 3 studies included a total of 763 patients. The therapeutic results are similar to those observed with tricyclics (2/3 good responders). Tolerability was significantly better. The onset of action was evaluated in 2 studies and was faster in the patients treated with moclobemide. The fact that reversible inhibitors of MAO-A demonstrate good efficacy independently of the diagnostic category of depression is an important new finding. PMID- 2248064 TI - Reversible and irreversible monoamine oxidase inhibitors in other psychiatric disorders. AB - In addition to being effective in depressive disorders, monoamine oxidase inhibitors (MAOIs) have been shown to be effective in controlled studies of patient with panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, posttraumatic stress disorder (PTSD) and borderline personality disorder. Uncontrolled case reports have noted MAOI efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia and avoidant personality disorder. Reversible inhibitors of MAO-A (RIMAs) appear safer than the classical irreversible MAOIs since they have less potential to increase blood pressure. They have not been studied as yet, however, in most of the conditions responsive to MAOIs. If RIMAs are found effective in these disorders, they would probably achieve wider use than MAOIs because they are safer and tend to cause fewer side effects. PMID- 2248065 TI - Moclobemide and the reversible inhibitors of monoamine oxidase antidepressants. PMID- 2248066 TI - Moclobemide versus placebo in the treatment of depression: a multicentre study in Belgium. AB - Moclobemide was compared with placebo for antidepressant activity, tolerance and safety in 2 parallel groups of 23 and 24 depressed patients. At the end of treatment (4 weeks or longer), 9 patients on moclobemide (41%) showed an improvement greater than or equal to 50% on the Hamilton Rating Scale for Depression, compared with only 4 (17%) of those on placebo. The overall assessment of efficacy was significantly better for moclobemide (good or very good results in 50% of patients) than for placebo (80% poor results). Moclobemide was well or very well tolerated by 85% of patients and placebo by 100%. Moclobemide was thus shown to be clearly more effective than placebo and only slightly less well tolerated. PMID- 2248067 TI - Moclobemide (Ro 11-1163) versus imipramine in the treatment of depression. AB - Moclobemide and imipramine were compared single-blind in 2 groups of 20 depressed patients (75% and 65% endogenous depression respectively). There was no significant difference between the 2 groups in improvement on the Hamilton Rating Scale for Depression. The final overall assessment of efficacy was good or very good in 80% of the moclobemide patients and 55% on imipramine. Tolerance was good to very good in 95% of moclobemide patients, compared with 80% on imipramine. No severe adverse effects were reported in either group. PMID- 2248068 TI - Moclobemide (Ro 11-1163) versus desipramine in the treatment of endogenous depression. AB - Moclobemide was compared with desipramine in 30 patients with endogenous depression. The Hamilton Rating Scale for Depression showed significantly greater improvement for moclobemide (69%) than for desipramine (45%). The final assessment of tolerance was good or very good in 87% of moclobemide patients compared with 13% of desipramine patients; 5 patients in the first group and all 15 in the second group complained of adverse effects. One patient on moclobemide and 5 on desipramine stopped treatment prematurely because of poor tolerance; no patients stopped treatment because of lack of efficacy. Assessment in this study was made difficult by concomitant treatment with benzodiazepines and/or mild neuroleptics in both groups, but the results of efficacy and tolerance clearly favour moclobemide over desipramine in the treatment of endogenous depression in hospitalized patients. PMID- 2248069 TI - Moclobemide versus clomipramine in the treatment of depression: a single-centre study, Federal Republic of Germany. AB - Moclobemide was compared with clomipramine for safety and efficacy in 2 groups of 15 patients each with endogenous depression. The drugs were given under double blind conditions in increasing doses; 1 patient in the moclobemide group dropped out because of lack of efficacy. Mean final improvement on the Hamilton Rating Scale for Depression was 51% in the moclobemide group and 54% in the clomipramine group. Efficacy and tolerance were rated good or very good by 47% (moclobemide) and 53% (clomipramine) (NS). The results indicate that moclobemide is as effective as clomipramine in treating endogenous depression. PMID- 2248070 TI - Moclobemide versus clomipramine in the treatment of depression: a multicentre trial in Spain. AB - The efficacy, tolerability and safety of moclobemide were compared with those of clomipramine in a double-blind, randomized parallel group study over 4 weeks. Patients were suffering from various forms of depression: 33 received moclobemide and 31 clomipramine. The mean score on the Hamilton Rating Scale for Depression decreased gradually in both groups, with no significant differences between them; the final scores showed an improvement of 57% in the moclobemide group and 60% in the clomipramine group, compared with baseline. The investigators' assessment of efficacy at the end of treatment was good or very good for 60% of moclobemide patients and 50% of clomipramine patients, and tolerance was good or very good for 31 patients on moclobemide and 26 on clomipramine. The drugs thus showed comparable antidepressant efficacy, and both were mostly well tolerated, although adverse events were more prevalent in patients treated with clomipramine. PMID- 2248071 TI - Moclobemide versus clomipramine in the treatment of depression: a double-blind multicentre study in Belgium. AB - Moclobemide and clomipramine were compared for efficacy, tolerance and safety in 63 mixed endogenous and nonendogenous depressed patients. Treatment was given for at least 4 weeks in a double-blind, randomized, parallel-group design. The mean Hamilton Rating Scale for Depression score decreased gradually during treatment with no differences between groups. Two patients on clomipramine and none on moclobemide were withdrawn for lack of efficacy, and poor tolerance caused 3 patients on moclobemide and 7 on clomipramine to stop treatment prematurely. Patients with endogenous depression responded better to clomipramine, whereas nonendogenous disorders did better on moclobemide. Adverse events were more frequent in the clomipramine group and more of these were severe or very severe than for moclobemide. Thus, although no significant difference in efficacy was seen, moclobemide appeared to be tolerated better than clomipramine. The numbers were small, however, and many patients received concomitant medication, and the results are therefore difficult to interpret. PMID- 2248072 TI - Moclobemide versus amitriptyline in the treatment of depression: two small double blind multicentre studies in Belgium. AB - Moclobemide was compared with amitriptyline for antidepressant efficacy, safety and tolerance. Two studies were conducted, both over at least 4 weeks; in the first, 8 patients were given moclobemide in doses ranging from 300 to 328 mg, and 9 patients amitriptyline in doses of 75 to 96 mg; in the second, the numbers were 13 on moclobemide and 14 on amitriptyline, and the mean doses were 294-408 mg and 95-129 mg respectively. Both studies showed the 2 treatments to be equally effective, and there were no significant differences at any point. Moclobemide appeared slightly more effective and slightly better tolerated than amitriptyline, but the numbers were too small for any valid conclusion. PMID- 2248073 TI - Moclobemide, imipramine and placebo in the treatment of major depression. AB - Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients. The dosage of moclobemide (25 patients) was 300 mg daily for the first 5 days, after which it could be increased to 600 mg. Imipramine (25 patients) was given in a dosage starting with 33 mg and gradually increased to 100 mg/day in the first 5 days, after which it could be further increased; 25 patients received placebo. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression, the overall assessment of efficacy and the Zung Self-rating Scale, and clearly superior to placebo; there were no significant differences between the 2 active drugs. Moclobemide was better tolerated than imipramine, and was almost comparable to placebo in this respect. PMID- 2248074 TI - Efficacy of a reversible monoamine oxidase-A inhibitor versus imipramine in subgroups of depressed patients. AB - Two multicentre studies comparing moclobemide with imipramine under similar conditions in patients undergoing a major depressive episode (DSM-III) were combined in the present analysis. A total of 353 patients received moclobemide (300-600 mg/day) and 356 imipramine (100-200 mg/day). In each study, the antidepressant efficacy of the 2 drugs was comparable, and subgroup analysis showed that moclobemide and imipramine were equally effective in endogenous depression. The response rate did not appear to be influenced by sex, but patients older than 60 years tended to respond less well to both drugs than did those under 60. The conclusion from the 2 studies is that, contrary to what is frequently stated for monoamine oxidase inhibitors, moclobemide appears as effective as a tricyclic in treating endogenous depression. PMID- 2248075 TI - Moclobemide versus tranylcypromine in the treatment of depression. AB - Moclobemide and tranylcypromine were compared in 2 randomized groups of 20 depressed patients each. Fifteen of the patients on moclobemide and 18 of those on tranylcypromine were diagnosed as suffering from endogenous depression. The dosage was 150-300 mg moclobemide and 15-30 mg tranylcypromine daily. At the end of treatment, improvement on the Hamilton Rating Scale for Depression was 59.3% in the moclobemide group and 65.5% in the tranylcypromine group. The final overall assessment of efficacy was good or very good for 68% of the patients on moclobemide and for 85% of those on tranylcypromine. The final assessment of tolerance was good or very good for 85% of the moclobemide patients and 100% of the tranylcypromine patients. None of the differences in scores between the groups were statistically significant. This study therefore yielded comparable results for efficacy and tolerance of the 2 drugs in the treatment of depression. PMID- 2248076 TI - Moclobemide (Ro 11-1163) versus tranylcypromine in the treatment of endogenous depression. AB - In this study, moclobemide (100-350 mg daily) was compared with tranylcypromine (10-30 mg daily) in 40 patients with endogenous depression. Treatment was randomly allocated and most patients also received benzodiazepines or mild neuroleptics concomitantly. Improvement on the Hamilton Rating Scale for Depression at the end of treatment was 66% for moclobemide and 41% for tranylcypromine patients. There were 3 suspected tyramine reactions in patients on tranylcypromine. Tolerance was considered good or very good for 95% of moclobemide patients, and for 75% of tranylcypromine patients. No clinically relevant changes in laboratory data were attributed to either of the trial drugs. The results clearly favour moclobemide over tranylcypromine for both efficacy and tolerance in the treatment of endogenous depression. PMID- 2248077 TI - Moclobemide compared with second-generation antidepressants in elderly people. AB - Two multicentre studies are described here; the first compared moclobemide with mianserin and the second with maprotiline, both in elderly patients with a DSM III diagnosis of major depressive episode. In the first study, 80 eligible patients were randomized to either moclobemide 300-500 mg or mianserin 75-125 mg per day for 4 weeks. Mean reduction in Hamilton Rating Scale for Depression (HRSD) score was 52% in both groups. The overall assessment of efficacy was good or very good for 60% of the patients, and tolerance was considered good or very good for 85% of the patients in both groups; no significant differences between the 2 treatments were seen. The second study comprised 39 hospitalized patients randomized to either moclobemide 150-300 mg daily or maprotiline 75-150 mg daily for 6 weeks. At the end of treatment, HRSD scores declined 85% in both groups compared with baseline. The overall assessment of efficacy was over 90% good or very good in both groups. Tolerance was rated good or very good for 80% of moclobemide and 75% of maprotiline patients; none of these results differed significantly between the groups, indicating that moclobemide is as effective in elderly patients as the 2 second-generation antidepressants. In view of the safety of moclobemide, it should be considered first-line therapy for depression in elderly people. PMID- 2248078 TI - Moclobemide (Ro 11-1163) safety in depressed patients. AB - Safety aspects were compared in 2203 patients given moclobemide and 1214 who received other antidepressants or placebo. A total of 2294 adverse events were reported by patients on moclobemide, mainly subjective symptoms (28.6%). Adverse events such as dry mouth, tremor, sweating, dizziness and constipation occurred much more frequently among 681 patients treated with various tricyclic antidepressants than in the 694 moclobemide patients with whom they were compared. Among 271 placebo-treated patients there were 287 adverse events, compared with 386 events in the 285 moclobemide patients in the same studies. Hypertensive episodes or food-drug interactions were reported by 19 patients on moclobemide and 5 on other antidepressants, but in only 2 of the former was ingestion of cheese a possible cause of headache. The assessment of tolerance on moclobemide was essentially the same as for placebo. Of the 1401 moclobemide patients in the electronic database, only 3.2% stopped treatment prematurely because of poor tolerance; the rates were higher for tranylcypromine, nomifensine, desipramine, clomipramine, amitriptyline and imipramine. During treatment, 6 patients attempted suicide with moclobemide alone (950-2000 mg) or together with imipramine (300 mg and 1200 mg). None of the intoxications was life threatening. PMID- 2248079 TI - Some basic aspects of reversible inhibitors of monoamine oxidase-A. AB - A novel class of antidepressants is emerging with considerable therapeutic potential: reversible inhibitors of monoamine oxidase type A (RIMA). Moclobemide (Aurorix) is a representative RIMA. It is a fully and rapidly reversible inhibitor of MAO-A with a correspondingly intermediate duration of action in vivo. It is free of hepatotoxicity and produces a much weaker potentiation of the tyramine pressor effect than the classical irreversible MAO inhibitors. Interaction of MAO inhibitors and monoamine reuptake inhibitors with tyramine is discussed on the basis of experiments in conscious rats. The issue of tyramine content of foods and beverages has been reinvestigated and its relevance for treatment with RIMA antidepressants is discussed. Recently observed antihypoxic (neuroprotective) effects of moclobemide suggest new indications for this compound. PMID- 2248080 TI - Potential of moclobemide to improve cerebral insufficiency identified using a scopolamine model of aging and dementia. AB - After a baseline performance assessment, 28 healthy male volunteers received subcutaneous injections of scopolamine hydrobromide to induce deficits in memory, attention and cognitive processes. Subsequent performance testing established the decrements caused by the scopolamine, and then each subject was given one of 3 investigational drugs including moclobemide, or placebo, according to a latin square design. Parallel versions of the test procedures were used to assess drug effects on the scopolamine-induced cognitive deficits. Whereas marked and statistically significant impairment was identified 60 min after scopolamine injection, the global analysis revealed statistically significant superiority of moclobemide over placebo at 120 min in relieving the scopolamine-induced decrement in performance. These results show that moclobemide may improve cognition in conditions associated with cholinergic deficit. It may therefore be especially indicated in the treatment of cognitive decline occurring with normal aging, depression in elderly people and Alzheimer's disease. PMID- 2248081 TI - Effects of moclobemide on sleep in healthy human subjects. AB - Ten healthy, normal subjects (5 male and 5 female) aged 20-28 years participated in this experimental study of the effect of moclobemide on sleep. The design consisted of 2 sessions of 5 nights each, comprising 1 adaptation night, 2 nights on placebo and 2 inputs of moclobemide 4 mg/kg (session B). The 2 sessions were separated by at least 15 days and their order was balanced and randomized. During the last 4 nights of each session, sleep parameters were recorded throughout the night according to standard procedures. Moclobemide at a dose of 4 mg/kg induced moderate changes in the sleep-wake balance: a significant increase in stage 1 on the second drug night, a slight increase in stage 2 and a significant decrease in paradoxical sleep on the 2 drug nights. There was also a moderate reduction in the number of rapid eye movements (REM) during paradoxical sleep, but the number of cycles and latency to paradoxical sleep were unchanged, as well as all other sleep parameters measured. With 6.5 mg/kg, the changes were more pronounced: total sleep time was diminished, but this was significant only on the second and third nights. Transient awakenings increased significantly on the first drug night, and wakening latency decreased. The only modification of orthodox sleep was an increase in the percentage of stage 2 on the first drug night, whereas slow-wave sleep was unchanged. Paradoxical sleep was reduced on the first 2 drug nights, but tolerance appeared on the third night. The decrease in paradoxical sleep was exacerbated in the last part of the night. REM were decreased during paradoxical sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248082 TI - Potentiation of the pressor effect of intravenously administered tyramine during moclobemide treatment. AB - Potentiation of the pressor effect of tyramine (TYR) by intravenous (i.v.) injection during moclobemide treatment was investigated in healthy volunteers and in depressed patients. The TYR sensitivity factor (TSF) is calculated as the ratio between the dose of TYR required to raise systolic blood pressure by 30 mmHg (TYR 30) without drug and that required with drug. After single-dose administration the TYR 30 for 100 mg moclobemide was 1.8 mg, and those for moclobemide 200 and 300 mg 1.6, compared with 3.2 for placebo, giving corresponding TSF values of 1.7, 2.0 and 2.0 respectively. Twenty-four hours after moclobemide intake, only the 300-mg dose yielded a mean TYR 30 value significantly different from placebo. The same doses of moclobemide given 3 times daily for 1 week resulted in a peak TSF of 2.0 with 100 mg, 2.9 with 200 mg and 3.3 with 300 mg (the latter dose being higher than normally recommended for 3 times daily administration). Nevertheless, 24 h after the last 300-mg dose the TSF was 1.2, similar to that of a single dose. In a study of 17 depressed female patients treated with moclobemide 100 mg 3 times daily, no relevant differences were found in TSF values from those of the volunteers. The authors conclude that, because of the short-lasting, reversible and selective MAO-A-inhibiting effect of moclobemide, there is no marked interaction with tyramine given by i.v. injection. No relevant difference was seen between depressed patients and healthy volunteers in the tyramine pressor effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248083 TI - Interaction between orally administered tyramine and moclobemide. AB - This article describes a standardized oral tyramine pressor test designed to give information on safety aspects in the real everyday life situation where tyramine is ingested only with food. Results showed that significantly higher doses of tyramine were required to raise standing blood pressure by at least 30 mmHg (TYR 30) when it was taken with food than when subjects fasted. The same test was then conducted in 8 healthy volunteers during treatment with moclobemide 200 mg 3 times daily and tranylcypromine 10 mg 3 times daily. With moclobemide the mean TYR 30 dose was 306 mg, and the ratio of this to baseline was 5.0. With tranylcypromine, however, the mean TYR 30 dose was only 35 mg and the TSF ratio 38.2. The potentiation by tranylcypromine was thus 7.6 times greater than that of moclobemide. When tyramine was given in the food under treatment with MAO inhibitors, the TYR 30 doses were larger than those obtained under fasting conditions, but the TSF ratios were not altered. When the tyramine was given in a protein-rich or a lipid-rich meal, the previously established TYR 30 had significantly less effect on the blood pressure. The lowest TYR 30 dose during moclobemide treatment is at least 150 mg tyramine, an amount contained in about 300 g strong cheese or 100 g of yeast extract. These quantities are unlikely to be consumed in a normal meal. The corresponding TYR 30 dose for tranylcypromine, however, is only 20 mg tyramine, which can easily be contained in a fairly normal portion of strong cheese (40 g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248084 TI - Relationship between tyramine potentiation and monoamine oxidase (MAO) inhibition: comparison between moclobemide and other MAO inhibitors. AB - The pharmacodynamic properties of moclobemide, a reversible inhibitor of MAO-A (RIMA), were compared with the properties of other reversible as well as older irreversible MAO inhibitors in human subjects. All the substances supposed to have MAO-A-inhibitory activity, with the exception of toloxatone, were shown by the decrease in plasma DHPG or MHPG levels to cause inhibition ranging between 50% and 85%. Toloxatone and low doses of deprenyl (a MAO-B inhibitor) caused 20% and 17% inhibition respectively; higher doses of deprenyl, however, strongly inhibited MAO-A. MAO-B inhibition was confirmed for all nonselective and selective MAO-B inhibitors. Moclobemide and clorgyline were found to be the most highly selective MAO-A inhibitors, although both also inhibited 30% of platelet MAO-B activity. Potentiation of the tyramine pressor effect is mainly influenced by the irreversibility and degree of MAO-A inhibition. Tyramine sensitivity was raised (a factor of 10-30) by all irreversible MAO inhibitors in doses inhibiting MAO-A; it diminished with increasing reversibility. In therapeutic doses, moclobemide potentiated the intravenous tyramine pressor effect 3 times less than the old irreversible MAO inhibitors; with the highest therapeutic dose, the tyramine sensitivity factor for moclobemide is only one-seventh to one-tenth that of tranylcypromine or phenelzine. Duration of action is obviously also closely related to the reversibility of inhibition: it ranged from up to 2 days with high doses of moclobemide to 3 weeks with tranylcypromine; clorgyline and phenelzine have been shown to maintain their action for several months. The new generation of RIMAs represents a significant progress in safety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248085 TI - Interaction studies with moclobemide. AB - Drug interactions with moclobemide given to healthy subjects and depressed patients are reviewed. The drugs investigated for safety were antihypertensives, digoxin, oral contraceptives, anticoagulants and benzodiazepines. Cimetidine was studied for the pharmacokinetic effect, and possible interactions with alcohol (stimulation and/or sedation) were included. Finally, since inhibition of monoamine oxidase (MAO) can increase noradrenergic transmission, possible interaction with neuronal reuptake inhibitors such as tricyclic antidepressants (TCAs) was investigated. Whereas replacement of the older, irreversible MAO inhibitors by a TCA was held to be dangerous and to require a therapy-free interval, the studies reviewed here provide evidence that amitriptyline can replace or be added to moclobemide without any sign of impaired tolerance, need for dose reduction or a therapy-free interval. Combined administration of moclobemide and desipramine was also tolerated well. Moclobemide did not interact with the direct-interacting sympathomimetics norepinephrine and isoproterenol and only to a negligible extent with phenylephrine. The combination of moclobemide with antihypertensive agents did not cause postural hypotension or an increase in other side effects. No clinically relevant interaction was observed between moclobemide and phenprocoumon, glibenclamide, oral contraceptives, digoxin or benzodiazepines. Cimetidine increased the concentration of moclobemide in plasma after a single oral dose by about 100%. If moclobemide is to be used in a patient pretreated with cimetidine, treatment should therefore start with the lowest therapeutic dose and then be adjusted to clinical needs. Since moclobemide is devoid of anticholinergic effects, no interaction with alcohol was anticipated. High therapeutic doses (600 mg/day) induced an effect similar to that of low doses of a TCA, but with 100-300 mg no interaction with alcohol was seen, even in elderly people. PMID- 2248086 TI - Biotransformation of moclobemide in humans. AB - The structure of the urinary metabolites formed after moclobemide administration in human was elucidated, and the pattern compared with that in the plasma. The metabolic pathways of moclobemide were also compared with those of structurally related substances. After oral moclobemide administration, on average 95% of the dose was recovered in the urine within 4 days, with a mean of 92% being excreted during the first 12 h. The drug is extensively metabolized: less than 1% of the dose was excreted unchanged. A total of 19 metabolites, accounting together for about 64% of the dose, was isolated and all metabolites accounting for more than 1% of the dose were identified. Consistent with other morpholine-containing compounds, metabolic pathways of moclobemide include mainly oxidative attack on the morpholine moiety, leading to a multitude of oxidation products. Four primary metabolic reactions were identified: morpholine N-oxidation, aromatic hydroxylation, morpholine C-oxidation and deamination. The major metabolites in urine are 4 carboxylic acids (M7A and M7B, M8, M9) that account for 49% of the dose. Only 2 metabolites (M3, M10) were found to be hydroxylated on the aromatic nucleus. They were excreted completely as conjugates of glucuronic and/or sulfuric acid. Conjugation in general, however, seems to be of minor importance in the overall biotransformation of the drug. The metabolite pattern in plasma was found to be qualitatively but not quantitatively similar to that observed in urine. Almost all of the main urinary metabolites were found in plasma as well. The unchanged parent compound and 2 primary oxidation products of the morpholine ring (M1, M15), which were present in urine only in trace amounts, could easily be detected in plasma. PMID- 2248087 TI - Pharmacokinetics of moclobemide after single and multiple oral dosing with 150 milligrams 3 times daily for 15 days. AB - This study was undertaken to determine the absolute bioavailability and steady state concentrations of moclobemide after doses of 150 mg. In 14 healthy human volunteers, no differences in tmax, t 1/2 beta, C1/F, Cmax and AUC were found between a single oral dose of 100 mg and one of 150 mg. The mean absolute oral availability was 0.66 and 0.69 respectively. Plasma concentration profiles of moclobemide on repeated dosing with 150 mg 3 times daily for 15 days were essentially superimposable, although the mean concentration was higher than after the single 150 mg dose. This concentration increased over the first week and then remained relatively constant. Mean accumulation factors for moclobemide during the first week were 1.85 for Cmax and 3.0 for AUC. These values were higher than predicted from single-dose characteristics. There was a marked reduction in the variability of AUC and clearance (C1/F) values at steady-state compared with the first dose. Minimum plasma concentrations of the 2 metabolites, Ro 12-5637 and Ro 12-8095, were relatively stable throughout dosing. The exact mechanism of the decrease in systemic and oral clearance of moclobemide with time during multiple oral dosing is not known at present. Either moclobemide inhibits its own clearance or moclobemide metabolism is inhibited by one or more of its metabolites. The findings indicate that, if dosage needs to be adjusted during treatment with moclobemide, the changes should be made carefully and at intervals of not less than 1 week. PMID- 2248088 TI - Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. AB - Three different studies were conducted to assess the pharmacokinetics of moclobemide in subjects with conditions complicating dose determination. The first examined the absorption and disposition of moclobemide in an elderly population and compared these with results obtained in a group of normal young subjects. No significant differences were found between the groups in the intravenous (i.v.) parameters of disposition, and no differences with regard to disposition of the metabolite, Ro 12-8095. In addition, the minimum steady-state concentrations of moclobemide and the main plasma metabolite did not differ between the elderly and younger patients. In the second study, clearance tests in patients with cirrhosis of the liver confirmed that hepatic function is drastically reduced in this group of patients; it is therefore possible that moclobemide absorption and distribution might be influenced. In only 3 of the 12 patients investigated, slowly declining plasma concentrations after administration pointed to a severely limited elimination capacity for moclobemide. In the remaining 9 subjects, average values of several parameters changed significantly (t 1/2 beta, MRT and C1), whereas Vss and renal clearance were not significantly altered. In patients with kidney dysfunction, there were no differences in kinetics between patients undergoing hemodialysis and those who were not. Compared with normal healthy volunteers, no differences were found for renal patients, with the exception of the mean absorption time, which was significantly prolonged. From these studies it can be concluded that, pharmacokinetically, neither age nor renal impairment require adjusting the dosage of moclobemide. Patients with liver cirrhosis, however, need to have the usual dose reduced to one half or one third, or else the dosage intervals can be increased to prevent cumulation. PMID- 2248089 TI - Comparison of the pharmacokinetics of moclobemide in poor and efficient metabolizers of debrisoquine. AB - A number of pharmacokinetics studies in which patients had been phenotyped and poor metabolizers for moclobemide found were analysed retrospectively. There were 27 subjects in all, aged between 19 and 75 years, and 5 of these were classified as poor debrisoquine metabolizers. Although there was a wide variability in the pharmacokinetic parameters observed, no consistent relationship was found between these and debrisoquine phenotype. Poor debrisoquine metabolizers all had values within the extremes for the efficient metabolism. This was true for both single and multiple dosing. This analysis is limited by the small number of subjects as well as its retrospective nature. Nevertheless, the data suggest that no deviations of moclobemide pharmacokinetics should be expected in poor metabolizers of debrisoquine compared with normal metabolizers. PMID- 2248090 TI - Health and poverty among elderly persons: a community-oriented primary care survey. AB - Providing health care for independent-living elderly persons is important, yet family physicians often lack accurate information about needs and access to care. The Community-Oriented Primary Care (COPC) approach and health status models from health services research provide a framework for assessing need and access to care. Personal interviews were conducted with 990 noninstitutionalized elderly persons in Youngstown, Ohio. Results showed that poverty, gender, and race were not strongly related to health status as measured by numbers of symptoms, functional status, or subjective health status. In addition, elderly persons had fewer health care needs and greater access to care than expected. Simple models of health status, need, and access do not seem to apply. The study shows the usefulness of COPC in planning health services; however, more effort is needed to refine measures of health status, need, and access. PMID- 2248091 TI - Papanicolaou smear cell recovery techniques used by primary care physicians. AB - Nine hundred Tennessee-based internists, family physicians, and obstetrician gynecologists were randomly selected and surveyed to identify Papanicolaou smear cell recovery methods used in their practices. This 16-item survey also requested typical laboratory reporting procedures on Papanicolaous smears. The most frequently reported cell sampling technique was the combination cotton-tipped applicator and spatula, which was used by 47 percent of all physicians. Use of the cervical cytobrush for Papanicolaou smears, which has been shown to improve the detection of cervical dysplasia, was used alone or in combination by 19 percent of those surveyed, of whom 72 percent were gynecologists. Cervical sampling should contain cells from the transformation zone as evidenced by an adequate number of endocervical cells on the smear. Laboratories reporting the presence of endocervical cells were significantly different (P less than 0.05) among the specialties, with 26 percent of the internists', 18 percent of the family physicians', and 15 percent of the obstetricians' laboratories not providing this information in their reports. Reporting inadequate smears is a necessary first step toward improved sampling technique. Without this information, physicians risk missing pathology through reports of false-negative Papanicolaou smears. PMID- 2248092 TI - Screening 1140 fifth graders for hypercholesterolemia: family history inadequate to predict results. AB - Cholesterol screening was performed on 1140 fifth-grade students in Scottsdale, AZ, as part of a school-affiliated, health-education program. The goals were to determine whether family history of heart disease or high cholesterol can predict which children have high cholesterol levels and to examine the feasibility of screening large numbers of elementary school students. Among the children studied, the mean cholesterol level was 168.3 mg/dL (4.35 mmol/L), and 13 percent had cholesterol levels above 200 mg/dL (5.20 mmol/L). Fifty-four percent had a family member with high cholesterol or a heart attack before age 60 years, but 36 percent of the students with cholesterol levels greater than 200 mg/dL (5.20 mmol/L) had a negative family history. Family history was neither sensitive nor specific as a predictor of elevated cholesterol levels (sensitivity 0.64, specificity 0.47, and positive predictive value 0.16 for predicting cholesterol levels greater than 200 mg/dL [5.20 mmol/L]). Large numbers of children were screened safely and efficiently with good student and parental cooperation. Results of this study do not support the current recommendations to screen children for hypercholesterolemia based upon their family histories. PMID- 2248093 TI - Asymptomatic rhabdomyolysis of unknown etiology. AB - A 7-year-old boy developed rhabdomyolysis with a peak creatine phosphokinase level of 261,400 IU/L after his appendectomy. These abnormalities occurred following a 2-3-day illness consisting of upper respiratory tract symptoms, fever, and abdominal pain mimicking acute appendicitis. At the time of operation, a normal appendix was removed, and mesenteric lymphadenitis was noted. The myoglobinuria and elevation of creatine phosphokinase were transient, and the patient remained asymptomatic. We review various causes of right lower quadrant pain and rhabdomyolysis and address the roles of malignant hyperthermia and infectious agents. The possible cause of the phenomena observed in this patient is discussed. PMID- 2248094 TI - The relation of serum cholesterol to risk of coronary heart disease: implications for the elderly. AB - Elevated cholesterol is a known risk factor for coronary heart disease (CHD) in young and middle-aged persons. Because of the high prevalence of CHD in a growing elderly population, physicians must decide whether to devote clinical attention to this condition in older patients. Longitudinal cohort studies show that while the association between serum cholesterol and CHD decreases after age 55 years, it still persists. Primary prevention trials performed mostly on middle-aged men have reduced the incidence rate of CHD through cholesterol lowering but they have yet to show a reduction in overall mortality. Secondary prevention studies of lipid alteration have reported decreased mortality and slowed progression of coronary stenoses, again in predominantly male subjects aged less than 60 years. Implications of these findings for care of older patients are discussed along with recommendations for clinical management and future research. PMID- 2248095 TI - Malignant melanoma presenting as nasal obstruction. AB - Mucosal melanomas arising in the nasal cavity are rare tumors comprising less than 1 percent of all melanomas. Often, the common clinical symptom is nasal obstruction. Grossly, they may or may not be pigmented and frequently attain large sizes. Histologic diagnosis of these tumors may be difficult, requiring immunohistochemical or electron microscopic confirmation. Aggressive surgical management is the treatment of choice in clinical stage I disease. Subsequent surveillance for recurrence is mandatory. Markers such as 5-S-cysteinyldopa may prove useful in staging, prognosticating, and postoperative surveillance for early recurrence, but their exact role has yet to be delineated. Ultimate prognosis is poor. PMID- 2248096 TI - Penetration of the pericardium by a gastric ulcer--survival after pericardiocentesis. AB - Elderly patients often have unusual manifestations of common illnesses. We describe a geriatric patient having a pneumopericardium from pericardial penetration by a gastric ulcer. Benign gastric ulceration causing perforation of the pericardium or other cardiac structures was recognized as early as 1854; however, until 1964, the condition was invariably fatal. Our patient survived the episode after early pericardiocentesis and medical treatment. Aspects of this uncommon clinical entity and a brief review of the literature are described. PMID- 2248097 TI - N-acetylcysteine in the treatment of human arsenic poisoning. AB - A 32-year-old man was brought to the emergency department 5 1/2 hours after ingesting a potentially lethal dose (900 mg) of sodium arsenate ant poison in a suicide attempt. The patient deteriorated progressively for 27 hours. After intramuscular dimercaprol and supportive measures failed to improve his condition, he was given N-acetylcysteine intravenously. The patient showed remarkable clinical improvement during the following 24 hours and was discharged from the hospital several days later. PMID- 2248098 TI - One family of generalists. PMID- 2248099 TI - Dorsal penile nerve block. PMID- 2248100 TI - Respiratory modulation of the cutaneous somatosympathetic reflex in normotensive (WKY) and in spontaneously hypertensive rats (SHR): species and strain-dependent patterns. AB - In 6 normotensive Wistar-Kyoto (WKY) and 6 spontaneously hypertensive rats (SHRs) anesthetized with urethane and chloralose, paralyzed, artificially ventilated, vagotomized with carotid sinus nerves bilaterally cut, somatosympathetic reflex discharges were recorded in cervical and renal nerves by stimulating group II and III cutaneous afferents in the sural nerve. Only a long-circuited, late supraspinal component reflex discharge could be elicited. After averaging the responses evoked by random stimulation, the latency of the reflex discharge was significantly longer in the renal than in the cervical sympathetic nerve, equally in the WKY rat and in SHR. In WKY rats the peak of sympathetic discharge corresponded to early expiration, whereas in SHRs--to late inspiratory phase. The duration of the reflex discharge elicited in inspiration was greater in SHR than in WKY rats. In WKY rats stimuli applied during phrenic discharge produced a reflex response of longer latency and of reduced amplitude than those applied in expiration. In SHRs the latency of the reflex response in the sympathetic cervical nerve was shorter during inspiration than in expiratory phase. The timing of the sympathetic reflex responsiveness within respiratory cycle in SHR and in WKY rats corresponded to strain-dependent opposite respiratory synchronization pattern of the spontaneous sympathetic activity characterizing each strain. No respiratory modulation of the somatosympathetic reflex was observed in the renal nerve of SHR. It is concluded that both spontaneous and evoked sympathetic activity is synchronized differently in SHR and in WKY rats and this difference is both species- and strain-dependent. PMID- 2248101 TI - Intracellular recordings from binocularly activated cells in the cat's dorsal lateral geniculate nucleus. AB - Five binocularly activated cells near the interlaminar layers of the dorsal lateral geniculate nucleus have been studied with intracellular recording techniques. Four neurons were relay cells and antidromically activated from the visual cortex. They received monosynaptic excitation and disynaptic inhibition from Y type retinal ganglion cells in both eyes and disynaptic recurrent inhibition. The fifth cell was similar to perigeniculate neurons. It received disynaptic excitation from retinal ganglion cells in both eyes and monosynaptic excitation from antidromically activated relay cell axons. It was also inhibited from all these sources after an additional synaptic delay. The cell had a large receptive field, about twice the center size of neighboring relay cells, and gave on-off responses from the entire response area. Such displaced perigeniculate like cells may explain why relay cells issue occasional axon collaterals within the dorsal lateral geniculate nucleus. PMID- 2248102 TI - Some aspects of brain morphology of the chronic cat and kitten preparations with brain stem transected at the pretrigeminal level. AB - In two adult cats and in three kittens aged from 8 to 11 days the brain stem was transected at the pretrigeminal level. The preparations were maintained from 7 to 79 days and processed histologically together with nonoperated controls. In kitten preparations brain was underdeveloped as shown by less numerous secondary sulci on the surface of the cortex. However, both cat and kitten preparations showed similar retrograde and anterograde neuronal degeneration. They also showed a similar transneuronal degeneration apparent in an increased density of neurons and their shrinkage in several structures investigated in the isolated cerebrum and the lower brain stem. Thus in kitten preparations a direct effect of transection predominated that of brain development. In the adult preparations at the level of transection a great accumulation of macrophages was found and the scar was built with connective tissue. In contrast, in kittens the transection scar was well delineated and built by astrocyte processes. PMID- 2248103 TI - Disturbances in sleep-waking pattern and cortical desynchronization after lateral hypothalamic damage: effect of the size of the lesion. AB - The effect of electrolytic lesions of varying size within the anterior part of the lateral hypothalamus (LH) on neocortical activity and quantitative sleep waking relations was studied in male Wistar rats. It was found that extensive LH lesions caused simultaneously an abolishment of cortical desynchronizing reactions and an electroencephalographic insomnia. More restricted damage left the qualitative pattern of cortical EEG unchanged, but still produced substantial reduction in the amount of sleep. Pronounced EEG disturbances coexisted with relatively mild behavioral deficits. It is concluded that a constellation of the LH syndrome symptoms is critically dependent on the variations of lesion parameters. PMID- 2248104 TI - Natural observations of smoking behavior: are there sex, age, context- or activity-related differences? AB - We unobtrusively observed 1979 people smoking one to three cigarettes in a variety of everyday activities. There were gender differences only with respect to group size and composition, and the time the cigarette was in the mouth. For most measures the correlations between behaviors were higher for men than women. There were few significant age differences in smoking behavior. We classified the activities of smokers into six broad categories: study, passive watching, active involvement, eating and drinking (non-alcohol), waiting rooms and alcohol related. There were significant differences in all measures (except time in mouth) as a function of the activity categories. Generally, smokers that were actively involved or passively watching had cigarettes lit for longer than smokers actively involved. Generally smokers that were actively involved took fewer puffs per cigarette than other smokers. Number of puffs per cigarette for all activity categories was lower than that reported from laboratory studies. PMID- 2248105 TI - The comparability of two commonly used carbon monoxide analysis systems: a technical note. AB - Carbon monoxide (CO) in expired breath is a common strategy for verifying smoking abstinence. The purpose of this investigation was to determine the comparability of two carbon monoxide (CO) analyzers: the commonly used Ecolyzer Series 2000 analyzer versus the new, highly portable, and less expensive Ecolyzer Model 210. Fifty-eight CO readings were obtained from 29 subjects (17 smokers, 12 nonsmokers) and analyzed on both systems simultaneously. Results indicated that the analyzers yielded highly comparable values for both smokers and nonsmokers. Moreover, the correlation between the two units' readings was very high (r = .92, p less than .001). There was, however, a significant analyzer by sex interaction with the Series 2000 analyzer yielding higher values for males. Overall, it was concluded that the Series 210 analyzer is a highly accurate and cost-effective instrument. PMID- 2248106 TI - Weight change among participants in a large sample minimal contact smoking relapse prevention trial. AB - Weight at baseline and posttreatment was measured for 1096 participants in a smoking relapse prevention trial: 42.1% maintained their weight, 42.5% gained more than 1 kg and 15.4% lost more than 1 kg during the eight-week treatment program. Abstainers (n = 383) gained more than four times the weight gained by relapsers (n = 713) (Abstainers: 1.6 kg, Relapsers: 0.4 kg, p less than .0001). In order to examine the anorexic properties of nicotine gum. Abstainers were classified into nicotine gum user and non-user categories. Users gained significantly less weight than non-users although the difference was small (Users: 1.1 kg, Non-users: 1.8 kg, p less than .004). A dose-response relationship was observed between number of cigarettes smoked per day at baseline and weight gain. Higher cigarette consumption was associated with increased weight gain in both gum user (p less than .004), and non-user groups (p less than .02). There was no significant difference in weight gain between Abstainers who later relapsed at 6 months and those who maintained abstinence (p less than .29). Although the impact of nicotine gum on weight gain was small, this apparent property of the substance may be useful in encouraging cessation among smokers who perceive weight gain as a potential stumbling block to success. PMID- 2248107 TI - Cue exposure as a practical treatment for addictive disorders: why are we waiting? PMID- 2248108 TI - The effects of exposure to drug-related cues in detoxified opiate addicts: a theoretical review and some new data. PMID- 2248109 TI - Integrating systemic cue exposure with standard treatment in recovering drug dependent patients. AB - Repeated drug administration readily produces classically conditioned responses in animal and human experimental studies. The majority of patients applying for treatment of drug dependence show both autonomic and subjective responses when exposed to drug-related stimuli. These responses are presumed to have been conditioned during a period of active drug use, persist after traditional treatment for drug dependence, and may constitute one of several factors which predispose to relapse. Preliminary data are presented from a novel treatment approach which is designed to test whether drug-conditioned responses can be reduced or extinguished by systematic exposure to drug-related cues and whether such extinction improves the overall results of treatment. PMID- 2248110 TI - What is presented, and what prevented, in cue exposure and response prevention with alcohol dependent subjects? AB - The following questions, pertaining to cue reactivity in alcoholics, are discussed: (a) What cues are relevant to alcoholics' drinking? Previous research has been concerned with the obvious: bottles, glasses, pub/bar environments, and other visual cues. Presumably more potent cues, that is, smell, taste and internal effects, subtle stimuli like social climate, shifts in conversations, also influence drinking. The effects of mood states on alcoholics' urges and behavior are rarely integrated into experimental studies. (b) What is the CR? Given that drinking is a very complex social behavior, "the drug effect" becomes problematic to disentangle from the effects of other factors, such as bio-medical states, social setting and learning history. This is further complicated by the fact that drugs affect physiological and cognitive systems differently at different dose levels and with rising and falling Blood Alcohol Levels. Moreover, it has been found that alcohol cues may elicit responses that are in the same and in the opposite direction to the drug response. (c) If such responses are reliably tied to alcohol cues (as opposed to novelty of the experimental situation), the impact of the conditioned responses on craving for alcohol and relapse becomes an issue. (d) Another question relates to the analogy between fear in phobias and craving in substance abuse since, unlike phobics, substance abusers do not fear the substance they are responding to. (e) A further issue is the effectiveness of extinction procedures, as opposed to changes in efficacy expectations, as a therapeutic mechanism for the cue exposure paradigm. Examples of recent research at the Hjellestad Clinic are presented. PMID- 2248111 TI - Conditioning processes and cue exposure in the modification of excessive eating. AB - Excessive eating is one of the principal characteristics of bulimia. Eating more than intended is also a prominent feature both of obese people who are trying to lose weight and normal weight women who are attempting to restrict their food intake. Overeating tends to be triggered by a specific set of cues, which commonly involve either mood disturbances or exposure to "forbidden" food, but may include other environmental cues. It is argued that conditioning processes are relevant both to the establishment of meal patterns in normal subjects and in the maintenance of excessive eating. Treatment procedures have typically followed the general approach of "Self Management" which emphasises reducing exposure to the cues associated with eating. An alternative approach derives from the idea that the association between eating responses (or urges to eat) and external cues may be learned, and therefore should in principle be ameanable to extinction through systematic unreinforced exposure. In this article the possible mechanisms of cue-induced overeating are discussed and the potential utility of cue exposure techniques for the management of excessive eating evaluated. PMID- 2248112 TI - Cue exposure and relapse prevention in the treatment of addictive behaviors. AB - Cue exposure techniques have been increasingly applied in the treatment of addictive behaviors. The role of cue exposure in a comprehensive approach to relapse prevention is considered from several theoretical perspectives. Issues discussed include the optimal definition of both cue and response variables in cue exposure, the relation between exposure to drug-taking cues and elicitation of outcome expectancies, and the combination of extinction-based cue exposure methods and skill training in relapse prevention programs. Whether cue exposure effects are mediated by extinction of appetitive craving responses and/or by the modification of efficacy and outcome expectancies is discussed. PMID- 2248113 TI - Efficacy of an incentive-based community smoking cessation program. AB - Although the number of smokers has declined in recent years, many people remain resistant to traditional smoking cessation programs. Therefore, new and innovative approaches have been attempted. This study describes the application and effects of a community-wide smoking cessation program over three successive years. Smoking cessation rates ranged from 10.6% (CO verified) to 30.1% (self report) at 1 month, and 17.3% to 24.5% at 1 year follow-up. Analyses revealed that successful quitters were more likely to have heart about the program at work and to have used materials contained in the self-help kit; and were more likely to be married and have a higher average income than either people who attempted to quit or made no attempt. Twelve-month follow-up data were used to classify participants into four new, distinct groups: maintainers, new quitters, relapsers, and nonquitters. Maintainers were more likely to have heard about the program at work and less likely to have become involved at Octoberfest. These programs do reach representative samples of the community. Their results compare favorably to other minimal contact intervention and physician-mediated efforts. PMID- 2248114 TI - Effect of parental smoking classification on the association between parental and adolescent smoking. AB - Prior studies of the relationship between smoking by parents and their children have considered only current smoking by parents. In this study of 12- to 14-year old adolescents, however, lifetime parental smoking was more strongly correlated with adolescent smoking than was current parental smoking. Indeed, lifetime parental smoking was as strongly correlated as peer smoking with adolescent smoking, and peer smoking is often considered to be the main determinant of adolescent smoking. These findings suggest that the relative role of parent smoking in adolescent smoking has been underestimated, and that new explanations for the association between parental and adolescent smoking are necessary. PMID- 2248115 TI - Alcohol-related cognitions: do they predict treatment outcome? AB - Relationships have been reported between alcohol-related cognitions and a range of demographic, drinking behavior, and drinking problem variables. There has been speculation that such cognitions might help predict treatment outcome. We investigated the ability of one class of alcohol-related cognitions--motivations (specifically, reasons for limiting drinking)--to predict the outcomes of a secondary prevention program. Heavily drinking university men were randomly assigned to three groups with different intensities of self-regulation training. Data from the combined sample (n = 40) were analyzed, since outcomes did not differ significantly by treatment level. Four motivation factors, alcohol consumption variables, and alcohol-related problems were assessed pre and posttreatment. Multiple regression analyses were used to assess the ability of pretreatment motivations to predict change on selected outcome measures. Two motivational factors were found significantly and differently related to program outcomes. Implications of these findings for future research and treatment effectiveness are discussed. PMID- 2248116 TI - Determinants of neuropsychological impairment in antisocial substance abusers. AB - Persons displaying Antisocial Personality Disorder (ASP) may be at risk for neuropsychological impairment due to a number of developmental and later life experiences to which they are prone. Thirty substance abusers meeting research criteria for ASP were compared to a demographically matched non-ASP cohort on neuropsychological test performance. The ASP subjects were found to have a higher prevalence of neuropsychological deficit. The groups were then compared on factors which might lead to brain impairment. Presence of ASP was associated with earlier and heavier past drinking patterns, more negative health and behavioral effects of alcohol abuse, and greater abuse of other drugs in addition to alcohol. The ASP alcoholics also reported a high prevalence of serious head injury (58%), although they did not differ from non-ASP alcoholics in this regard. Implications for the neuropsychology of alcoholism and for treatment are discussed. PMID- 2248117 TI - Adolescents' first and most recent use situations of smokeless tobacco and cigarettes: similarities and differences. AB - This study compared first and most recent use situations of adolescent smokeless tobacco experimenters with those of adolescent cigarette experimenters. Structured, open-ended interviews were conducted with 320 seventh and tenth grade youths in 16 Southern California schools. Students were categorized as nonusers (those who had never experimented with any tobacco product), minimal experimenters (those who had experimented with smokeless tobacco or cigarettes between 1 and 9 times), and persistent experimenters (those who had experimented with smokeless tobacco or cigarettes 10 or more times). The situations reported by smokeless tobacco were similar to those reported by cigarette experimenters. The most important differences between the two groups are highlighted. In particular, smokeless tobacco users seemed less concerned about negative social consequences of use than cigarette smokers. In addition, nonusers' observations of use and implications for prevention and cessation are discussed. PMID- 2248118 TI - Stages of adolescent tobacco-use acquisition. AB - The present study extended the results of previous research in applying the "stages of acquisition" model to the onset of smokeless tobacco as well as cigarette use. Three expert judges classified an initial pool of items as to whether they represented "precontemplation," "contemplation," "action," or "maintenance" stages of smokeless tobacco acquisition. Fifty items with adequate inter-rater reliability were combined with 21 previously developed items pertaining to cigarette smoking acquisition in an overall tobacco acquisition questionnaire, which in turn was administered to 358 junior and senior high public school students. Three distinct components labeled precontemplation, action, and maintenance were delineated through principal component analyses. Coefficient alphas and discriminant analyses according to self-reported use demonstrated adequate reliability and validity for the new smokeless tobacco- and previously developed smoking-acquisition scale. PMID- 2248119 TI - Differences between white and black youth who drink heavily. AB - This study compares the attitudes and beliefs of white and black adolescents who drink heavily. The study's sample comprises 1,533 youth who responded in 1987 to a survey of 10,259 7th to 12th grade students, and reported that they had gotten drunk at least six times within the previous year. The ratio of blacks to whites decreased with drinking severity. Controlling for age, sex, and living situation, a logistic regression revealed that blacks were significantly more likely than whites to believe that getting drunk would lead to health problems and that alcohol is addicting. Blacks were also more concerned than whites about their parents' disapproval of their drinking alcohol, while whites were more concerned than blacks about their friends' disapproval. The study suggests that programs targeted towards black youth who drink heavily should focus less on enhancing peer refusal skills and more on ensuring that black parents and other adults make explicit their negative attitudes towards alcohol use. PMID- 2248120 TI - Development and validation of the situational appetite measures. AB - Based on a system to categorize high-risk situations for relapse in addictive disorders, instruments were developed to assess cue strength and self-efficacy relevant to weight loss attempts. Two versions of the Situational Appetite Measure (SAM) were developed, one to assess urges to overeat in selected situations and the other to assess self-efficacy in controlling urges to overeat. In a sample of college student dieters and enrollees in commercial diet centers, the measures were found to be highly correlated, such that as consummatory urges increased, self-efficacy to control overeating decreased. High-risk situations were represented by five relatively distinct and reliable subscales: relaxation, food present, hunger, reward, and negative feelings. Low cue strength and high self-efficacy for controlling overeating in situations involving negative feelings predicted weight reduction among female dieters in treatment. The multidimensional nature of the SAM allows for differential prediction of eating behavior across situations. PMID- 2248121 TI - An individualized cognitive intervention: does it increase the efficacy of behavioral interventions for obesity? AB - This study examined the effectiveness of the addition of a cognitive intervention based on individualized assessment to a behavioral intervention. Sixty-three subjects who were at least 15% overweight were randomly assigned to a behavioral intervention or a behavioral intervention and a cognitive intervention focused on changing specific maladaptive self-statements related to weight loss. It was predicted that the behavioral and cognitive intervention would result in greater weight loss and reduction in body fat than the behavioral alone intervention at posttest and at 3-month follow-up; results did not support this hypothesis. Support was found for the construct validity of the behavioral intervention with significant differences between time points on behavioral measures observed. On the cognitive measures, both treatment conditions showed changes over time on cognitive measures, but differences between the treatments were not significant. Based on the results of this study, it is suggested that future research examining the effectiveness of cognitive interventions in the area of weight loss include measures other than those that are weight-related, longer follow-ups to assess long-term maintenance, and sufficient amounts of cognitive therapy so that clients have fully integrated the newly learned cognitive dialogues into their everyday lives. PMID- 2248122 TI - Drug use, health, family and social support in "crack" cocaine users. AB - The purpose of this study was to explore and describe "crack" cocaine use, health, family and social support in adult users. A nonprobability, convenience sample was used comprising 100 inpatients, 77 men and 23 women, from a drug treatment program. Gender differences, though not found in areas related to drug consumption, were found with respect to where and with whom subjects smoked, as well as perceptions of significant others. This initial, exploratory study should provide a foundation for future investigations concerning crack cocaine users. PMID- 2248123 TI - The development of a Short Opiate Withdrawal Scale (SOWS). AB - In previous studies a 32-item Opiate Withdrawal Scale was found to provide a reliable and valid means of measuring the signs and symptoms of withdrawal among heroin (and other opiate) addicts. This paper describes the processes whereby a shorter 10-item version of the same scale was developed. The Short Opiate Withdrawal Scale (SOWS) is simple to understand and easy to administer, and it avoids the redundancy of items contained in the original scale. It is suggested that the SOWS provide a useful instrument which can be used both in research and clinical practice with opiate addicts. PMID- 2248124 TI - The role of drinking restraint success in subsequent alcohol consumption. AB - Intentional self-restraint may play an important role in the control of potentially addictive behavior. Unfortunately, for some individuals, efforts to reduce substance use may prove not only temporary but to increase the likelihood of a later "binge." An experimental study examined the relationship between prior self-restraint efforts and drinking. Results indicated that successfully restrained drinkers (i.e., those individuals who reported exerting considerable effort toward drinking self-control, and who were normatively successful, that is, light drinkers) responded to the sudden availability of alcohol with increased levels of consumption, relative to unrestrained drinkers at a similar level of habitual drinking. There was no such effect among unsuccessfully restraining (i.e., heavy) drinkers. These results suggest that a period of successful drinking restraint which is initiated by the individual, may lead to heightened subsequent alcohol consumption. PMID- 2248125 TI - Pathological gambling treated with cognitive behavior therapy: a case report. AB - A novel approach to the cognitive behavioral treatment of pathological gambling is described. The approach is based on the hypothesis that biased information may form the basis of the rules governing gambling behavior. The treatment focused on modifying assumptions and beliefs underlying the gambling behavior of a 47-year old male with a 26-year gambling history. Based on a 6-month follow-up, the intervention successfully reduced the frequency of the client's gambling behavior from 10 times per month in the 3 years prior to treatment to three total times in the 6-month follow-up period. PMID- 2248126 TI - Spermicides, hormonal contraception and congenital malformations. PMID- 2248127 TI - Present status of contraceptive vaginal rings. PMID- 2248128 TI - Steroidal contraceptives and changes in individual plasma phospholipids: possible role in thrombosis. AB - The changes in the levels of individual phospholipids were studies in women during prolonged use of three types of steroidal contraceptive preparation: high dose combined pills (Noriday 1 + 50 Fe); low-dose combined pills (Nominest Fe) and progestin-only injectables (Depo-Provera). Women on high-dose combined pills had significantly higher (p less than 0.05) mean lysophosphatidylcholine (LPC), sphingomyelin (SPH), phosphatidylserine (PS) and phosphatidylethanolamine (PE) levels, respectively, than the women on low-dose combined pills, progestin-only injectables and the controls, respectively. Women on low-dose combined pills had significantly lower (p less than 0.01) mean LPC and PS levels, respectively, than the controls, while women on progestin-only injectables had significantly lower (p less than 0.01) mean PS and PE levels, respectively, than the controls. Based on the reported high activities of PS and PE in hemostasis, the PE/total plasma phospholipids, PS/total plasma phospholipids and the sum of PE and PS/total plasma phospholipids ratios were calculated to assess the possible overall effect of the changes in plasma phospholipids in steroidal contraceptive users. The results obtained using these indices agree with some earlier reports of an estrogen dose-dependent risk/incidence of thrombosis in steroidal contraceptive users. It is concluded that the observed dose-dependent estrogen-induced alterations in phospholipids, and, most especially, the PE and PS fractions may bear a relationship with thrombotic conditions. PMID- 2248129 TI - Safety of intrauterine contraception. AB - Some of the risks which have been associated with the use of intrauterine contraception are reviewed. For users of copper-releasing IUDs, such as the Multiload Cu375 and TCu380, uterine perforations are rare, there is no evidence of an increased risk of infertility, and there probably is no increased risk of ectopic pregnancy after IUD removal. Any increased risk of pelvic inflammatory disease may be limited to the initial months of IUD use. The safety of intrauterine contraception needs to be re-evaluated for the newer IUDs, since most of the information relating to IUD safety is based on studies of devices which are no longer used or which are not in widespread use. PMID- 2248130 TI - The proliferation and fusion of myoblasts in vivo. PMID- 2248131 TI - The DMD gene promoter: a potential role in gene therapy. AB - The studies I've outlined here are obviously at a preliminary stage but do offer some insight into the complexity of DMD gene regulation and do suggest that an understanding of this regulation may have some potential benefit in gene therapy for this disease. The high promoter activity found was unexpected and suggests that in vivo the activity of the endogenous gene may be repressed by elements not present within this region. Of course, other interpretations are possible. The transcripts in vivo may turn over very quickly, or the very large size of the DMD gene may in itself limit the rate of transcription. Alternatively, the gene may be actively transcribed only during the early stages of differentiation. A more detailed analysis of developmental expression and of DNA sequences surrounding exon one is required to address these alternatives, but the possibility for augmenting dystrophin synthesis during myoblast therapy clearly exists. The high level of activity and the tissue and developmental specificity exhibited by the HP2 construct suggest this may be the promoter of choice in future gene therapy experiments. The high degree of specificity shown by this promoter would reduce the need to target gene constructs to muscle cells and would reduce the potential complications of uncontrolled gene expression. Of course, before any of these benefits could be realized much more work must be done both in analysing DMD gene expression and in testing potential gene therapy constructs both in culture and in animal models of this disease. PMID- 2248132 TI - Regeneration of skeletal muscle fibers after necrosis. PMID- 2248133 TI - Fibroblasts fuse with myotubes developing in culture. PMID- 2248134 TI - Control of satellite cell proliferation. PMID- 2248135 TI - Regeneration of skeletal muscle induced by satellite cell grafts. PMID- 2248136 TI - Localization of muscle gene products in nuclear domains: does this constitute a problem for myoblast therapy? PMID- 2248137 TI - Detection of truncated dystrophin in fetal DMD myotubes. AB - An immunohistochemical study was carried out on a twelve-week old fetus, aborted for high risk of Duchenne muscular dystrophy. Southern and FIGE analysis showed an intragenic duplication in the DMD gene, which had previously resulted in a severe Duchenne phenotype in three relatives. Polyclonal antibodies directed against the NH2-terminal half of dystrophin showed a positive reaction an a similar distribution of dystrophin in the skeletal myotubes of a twelve-week old normal fetus and the affected fetus. In contrast, a polyclonal antibody directed against the COOH-terminus of dystrophin, i.e., distal to the mutation in this family, did only react with the myotubes of the normal fetus and not with those of the affected fetus. This indicates the presence of a truncated dystrophin in the affected fetus. Apparently at this stage, before binding of dystrophin to the sarcolemma, no distinction is made yet between normal and abnormal dystrophins. This implies that the potential to bind to the sarcolemma could be a major point of discrimination between normal and defective dystrophins. The truncated dystrophin will probably be degraded in a later stage during fetal development. So it appears that the use of dystrophin immunostaining to confirm high Duchenne risk abortions requires great caution. To prevent false-positive results, the combined use of NH2- and COOH-terminal antibodies is mandatory. PMID- 2248138 TI - Mouse chimeras and genetic rescue of mosaic muscle. AB - The nuclear-cytoplasmic relationships existing within mosaic muscle will likely determine whether myoblast transfer can effectively rescue diseased muscle. The mouse chimera preparation is one source of such mosaic muscle in which that in vivo relationship can be investigated in the complete absence of complicating immunological or surgical trauma. For several metabolic enzymes, the mature muscle fiber appears to contain a homogeneous mix of the proteins encoded by multiple myonuclei. This relationship is clearly not representative of all muscle proteins, as several examples of proteins highly localized to "nuclear territories" have now been described. Nonetheless, the intrafiber distribution of certain enzymes, particularly GP1-1, is appropriate for the basis of a genotype marking system applicable to mosaic fibers. In vitro rescue of mdg myotubes is readily achievable by incorporation of few normal myonuclei and possibly by only one. In vivo requirements are apparently far more stringent and an hypothesis in which the mdg gene product, a Ca+(+) channel subunit, is restricted to nuclear territories would be consistent with the disparate results obtained in vitro and in vivo. Finally, chimeras containing mdx/mdx cells may show a partial amelioration of muscle pathology and may provide a means of determining the minimum genetically normal myonuclear compliment required to prevent degeneration of dystrophin-deficient fibers. PMID- 2248139 TI - Improved media for rapid clonal growth of normal human skeletal muscle satellite cells. PMID- 2248140 TI - Myogenic conversion of human non-muscle cells for the diagnosis and therapy of neuromuscular diseases. PMID- 2248141 TI - Genetic and biochemical determinations in the pre-transplant workup and in the post-transplant assessment period. PMID- 2248142 TI - Use of quantitative myometry in the evaluation of myoblast transfer therapy. PMID- 2248143 TI - Issues in myoblast transfer. PMID- 2248144 TI - Quantitation of muscle mass and muscle protein synthesis rate: documenting a response to myoblast transfer. AB - Initial trials of myoblast transfer into individual muscles should include studies of regional muscle mass. Magnetic resonance imaging is a safe and accurate technique that should be studied in the context of these trials. Creatinine excretion should also be measured in order to provide baseline information for future studies of myoblast injections into a larger number of muscles. In vivo assessment of muscle protein synthesis can be combined with histologic study to determine if the treatment alters the rate of protein synthesis. PMID- 2248145 TI - Plausible structural/functional/behavioral/biochemical transformations following myoblast transfer therapy. PMID- 2248146 TI - Mdx mouse as therapeutic model system: development and implementation of phenotypic monitoring. PMID- 2248147 TI - Golden retriever muscular dystrophy: monitoring for success. PMID- 2248148 TI - The role of the xmd dog in the assessment of myoblast transfer therapy. PMID- 2248149 TI - The dilemma of manifesting carriers in the context of myoblast transplantation. PMID- 2248150 TI - Immunosuppressive therapy in Duchenne muscular dystrophy: considerations for myoblast transfer studies. PMID- 2248151 TI - MyoD: a regulatory gene of skeletal myogenesis. PMID- 2248152 TI - Immunological aspects of histoincompatible myoblast transfer into non-tolerant hosts. PMID- 2248153 TI - A comparison of long-term survival of muscle precursor cell suspensions and minced muscle allografts in the non-tolerant mouse. PMID- 2248154 TI - N-CAM is a target cell surface antigen for the purification of muscle cells for myoblast transfer therapy. PMID- 2248155 TI - Immunochemical analyses of the myoblast membrane and lineage. PMID- 2248156 TI - The principles and practice of myoblast transfer. PMID- 2248157 TI - Myoblasts, satellite cells, and myoblast transfer. PMID- 2248158 TI - Myoblast transfer improves muscle genetics/structure/function and normalizes the behavior and life-span of dystrophic mice. PMID- 2248159 TI - Practical aspects of myoblast implantation: investigations on two inherited myopathies in animals. PMID- 2248161 TI - [Present status of extraocular muscle research]. PMID- 2248160 TI - Purification and proliferation of human myoblasts isolated with fluorescence activated cell sorting. PMID- 2248162 TI - [Isotonic contraction of rabbit superior rectus muscle]. AB - It is well known that the mammalian extraocular muscle has slow muscle fiber morphologically. But the contraction speed of slow muscle fiber has not been mentioned in previous reports. We studied the isotonic contraction of slow muscle fiber and compared it with fast muscle fiber. Each fiber bundle was isolated from the rabbit superior rectus muscle. Both light microscopic findings and the reaction to isotonic contraction in Ca2+ free Ringer's solution could identify each of the two muscle fiber types. Contraction speed depended on the frequency of stimuli (40-200 Hz) in both slow and fast muscle fiber. Maximum velocities of slow and fast fiber bundles were 4.3 +/- 1.53 mm/sec and 26.9 +/- 3.48mm/sec at 200Hz, respectively. It was suggested that the relaxation of slow muscle fiber did not interfere with the contraction of the fast muscle fiber. The relation between contraction velocity and afterload showed an approximately right angle hyperbolic curve. PMID- 2248163 TI - [Responses in extraocular muscles from magnetic stimulation of the cat brain]. AB - In 12 adult cats, pulsed magnetic stimuli were applied to the scalp, with the center of the stimulating coil over the interparietal bone. Recordings were obtained from the superior rectus, lateral rectus and inferior oblique muscles with concentric needle electrodes. In all cats, single muscle action potentials were recorded easily in all the muscles examined with latencies of 3.2-37.5 ms (mean 15.6ms). These responses disappeared after intravenous administration of pancuronium bromide. Furthermore, the elicited action potentials in the inferior oblique muscles disappeared by amputation of the inferior oblique branch of the oculomotor nerve. In some motor units, stronger stimuli shortened the latency of the responses. In most units, however, stimulus intensity did not influence the latency of responses over a wide range. The mean latency (15.6ms) is coincident with the latency of cortical spike potentials preceding voluntary saccades. This remarkable coincidence suggests that our pulsed magnetic stimuli have a very strong possibility of generation of human saccades. Thus, magnetic stimulation of the scalp may provide further information relevant to the normal operation of the oculomotor system. PMID- 2248164 TI - [Evaluation of experimental proliferative vitreoretinopathy in rabbits]. AB - We established an effective animal experimental model for proliferative vitreoretinopathy (PVR) by intravitreally injecting cultured cells in order to investigate therapies for PVR, including intravitreal drugs, radiation and hyperthermia. After making posterior vitreal separation by injecting SF6 gas into the rabbit's vitreous body, cultured cells were intravitreally injected. Fundus changes were followed up for 4 weeks and PVR stage was recorded according to the classification described by Hida et al. The cultured cells injected were rabbit dermal fibroblasts (5 x 10(4) and 10 x 10(4) and human retinal pigment epithelial (RPE) cells (5 x 10(4]. A total of 37% of animals reached STAGE 5-7 (traction retinal detachment) in 4 weeks in 41 eyes injected with 5 x 10(4) rabbit fibroblasts and were 86% in 14 eyes injected with 10 x 10(4) rabbit fibroblasts. The 10 eyes injected with human RPE cells showed STAGE 2 or less in 4 weeks. Consequently, we selected the experimental PVR model using injecting of 10 x 10(4) rabbit fibroblasts as the most effective method. PMID- 2248165 TI - [Dye laser photocoagulation treatment for experimental subretinal neovascularization. 1. Histopathological findings of healing process]. AB - To clarify the healing process of subretinal neovascularization (SRN) histopathologically following laser photocoagulation treatment, we performed laser photocoagulation for experimental SRNs produced in rhesus monkey eyes. To produce long-lasting SRNs, 0.5M 1-ornithine hydrochloride solution was injected intravitreously 2 weeks after photocoagulation. These SRNs were treated a 590nm dye laser, and examined clinically and histopathologically at 24 hours, 2 weeks, 3 months. Histopathologically, new vessels in the subretinal space were coagulated intensely and disappeared during the course of healed lesion. In these lesions, the retinal pigment epithelial cells proliferated in the subretinal space after the disappearance of the SRNs and covered the scar tissue. In strongly coagulated lesions, glial cells were related to the formation of scar tissue. These results showed that closure of new vessels was necessary for the healing of SRNs by photocoagulation and proliferation of the retinal pigment epithelial cells and glial cells occurred during their healing process. PMID- 2248166 TI - [Dye laser photocoagulation treatment for experimental subretinal neovascularization. 2. Histopathological findings of unsuccess lesions]. AB - We observed the histopathological process in unhealed lesions following photocoagulation treatment for experimental subretinal neovascularization (SRN) in rhesus monkey eyes. Long-lasting SRNs were produced experimentally by the method which we previously reported. These SRNs were treated by a 590nm dye laser beam, and were examined clinically and histopathologically. Lesions in which insufficient photocoagulation treatment was performed showed serous fluid accumulation and fluorescein angiography revealed remaining neovascularization. In these lesions abundant patent neovascularization was seen with proliferation of spindle-shaped fibroblast-like retinal pigment epithelial (RPE) cells in the subretinal space. These metaplastic RPE cells produced matrix and abundant collagen fiber around the cells. The above results showed that insufficient photocoagulation induced neovascularization and proliferation of RPE cells in the subretinal space and promoted the formation of fibrovascular membrane. PMID- 2248167 TI - [Delayed development of binocular function in the long postoperative period of infantile esotropia]. AB - Long-term observation of binocular function was carried out in 30 postoperative cases of infantile esotropia. The period of observation was 5 to 12 years and the targets used for evaluation were deviating angle and stereo acuity. In the successful group, 20 cases out of 30 (67%) achieved a stereo acuity of 60 seconds or better. Among the remainder, partial improvement was seen in 20% and no improvement in 13%. Preexisting amblyopia and ARC improved in the successful group, and the final deviating angle was a mean of 2.3 prism diopter. There were 2 types of cure processes in the successful group. The first group achieved a good binocular function in a relatively early postoperative stage (7 cases), while the second group had delayed development of binocular function over a period of several years (13 cases). The former cases had sufficient orthoptic treatment during admission and the latter showed a gradual improvement of stereo acuity accompanied by good eye position. It has been generally accepted that the rate of binocular function recovery is very poor among cases of infantile esotropia, but our study revealed that skillful orthoptics administered by a selected member of our team over an extended period enabled the achievement of good binocular function in infantile esotropia. PMID- 2248168 TI - [Pointing response before and after strabismus surgery]. AB - Eye-hand open-loop pointing responses were measured in eight patients before and after unilateral strabismus surgery. They showed large shifts in pointing responses with the operated eye and relatively small ones with the non-operated eye. The same pointing responses were examined in five normal subjects. Statistically significant shifts were found even in cases of normal subjects. From these results, it was speculated that visual localization and eye-hand coordination may change by some unknown factors or under casual conditions. PMID- 2248169 TI - [Measurement of incomitance patterns of vertical deviation in superior oblique palsy with a synoptometer]. AB - By using a synoptometer we tried to compare the incomitance pattern of the vertical deviation in congenital superior oblique palsy with that of the vertical deviation in acquired superior oblique palsy. The data were transformed to a three-dimensional format by a computer to classify the incomitance pattern. With this method we found a difference in the incomitance pattern between congenital and acquired superior oblique palsy. In cases of congenital superior oblique palsy the vertical deviation increased proportionately with the change of gaze from abduction to adduction, since the incomitance caused by the horizontal change of gaze was more marked than that of the vertical change of gaze. However in cases of acquired superior oblique palsy the vertical deviation increased proportionately with change of gaze from up- to downward positions, therefore the incomitance caused by vertical change of gaze was more marked than that of the horizontal change of gaze. Moreover congenital superior oblique palsy was classified into three types according to the classification of Wieser and their incomitance patterns of vertical deviation were compared with each other. PMID- 2248170 TI - [Surgical effect on incomitance of vertical deviation in superior oblique palsy measured by a synoptometer]. AB - Using a synoptometer we evaluated the surgical effect on the incomitance of the vertical deviation in 26 patients with congenital superior oblique palsy. Either an inferior oblique recession or a superior oblique plication was performed. The two operative procedures reduced the incomitance caused by horizontal change of gaze, but produced incomitance by the vertical change of gaze and the incomitance increased proportionately with change of gaze from down to upward positions, which was not recognized preoperatively. As a result, the hyperdeviation was markedly reduced in the field of action of the overacting inferior oblique muscle. Moreover the surgical effect on the incomitance of the vertical deviation was studied in 13 patients with acquired superior oblique palsy treated with superior oblique plication. This procedure increased not only the incomitance in the upward positions by horizontal change of gaze, but also produced incomitance in adductive positions by vertical change of gaze. Therefore the hyperdeviation of the paretic eye was remarkably overcorrected in the field of action of the antagonist of the paretic superior oblique muscle. PMID- 2248171 TI - [Histopathological observations on orbital fatty tissue in dysthyroid ophthalmopathy]. AB - Seventeen specimens of orbital fatty tissue taken from cases of dysthyroid ophthalmopathy at the time of operation were observed by light and electron microscopy, and also by immunohistochemical staining. The pathological changes observed were infiltration of the chronic inflammatory cells, deposit of fibrin, sclerosis of vascular wall, occlusion of the vascular lumen, and accumulation of hydrophilic mucopolysaccharide. Immunoglobulin G was detected in fat cells and lymphocytes, and some of the infiltrating lymphocytes were determined to be T cells, by immunohistochemistry. These findings suggested that the pathology of the dysthyroid ophthalmopathy was closely related to the chronic inflammation induced by the immune reaction. The exophthalmos was considered to occur due to edema secondary to chronic inflammation and accumulation of the mucopolysaccharides. PMID- 2248172 TI - [Exfoliative materials in the skin of patients with exfoliation syndrome]. AB - The iris and the skin of the lateral canthus of patients with exfoliation syndrome were studied by light and electron microscopy. The materials were surgically obtained from 9 patients of cataract and/or glaucoma associated with exfoliation syndrome. For the control study, we prepared the iris and the skin of 6 patients without exfoliation syndrome. In all 9 cases of exfoliation syndrome, exfoliative materials were observed in the pigment epithelium of the iris. In 3 of 9 cases, exfoliative materials were found in the dermis. In 6 other cases, microfibrils and immature forms of exfoliative materials were observed, but not typical forms. Neither in the iris nor in the skin of the control cases were exfoliative materials detected. Exfoliative materials in the dermis seen in the patients with exfoliation syndrome were morphologically similar to those in the iris. This is the first report of demonstration of exfoliative materials in the skin. These observations suggest that exfoliation syndrome may be a systemic degenerative disorder of the body. PMID- 2248173 TI - [The relationship between ophthalmoscopic changes and classification of toxemia in toxemia of pregnancy]. AB - Based on ophthalmoscopic findings, 30 toxemic patients were divided into three types: R-type; retinal vascular occlusion type, C-type; choroidal vascular occlusion type, R + C-type; mixed vascular occlusion type. R-type (5 cases) and R + C-type (7 cases) significantly correlated to superimposed preeclampsia. C-type (18 cases) significantly correlated to preeclampsia (pregnancy-induced hypertensive disorder: PIH). Clinical examinations (urine protein, platelet, fibrinogen, fibrin degradation product, partial thromboplastin time and prothrombin time) had no relation to the types of ophthalmoscopic classification. It was concluded that preeclampsia (PIH) and superimposed preeclampsia have different influences on the ocular fundus. PMID- 2248174 TI - [Two cases of idiopathic preretinal macular fibrosis in children]. AB - We report herein the findings in two patients less than 15 years old with the diagnosis of idiopathic preretinal macular fibrosis, a disorder found primarily in the older population. Only a few reports have discussed idiopathic preretinal macular fibrosis in children and its pathogenesis is still unknown. One is a 10 year-old boy and the other is a 14-year-old girl who visited our hospital with a chief complaint of blurred vision in their right eyes. Epiretinal membranes were recognized on the macular region of their right eyes. Since there was no causative factors, a diagnosis of idiopathic preretinal macular fibrosis was made. They were conservatively followed up. The vision of the boy once worsened but improved spontaneously and remained stable for three years. Because the vision of the girl worsened rapidly, vitreous surgery was performed to remove the epiretinal membrane, resulting in poor vision. It was suggested that this disorder in children should be followed up conservatively and the indication of vitreous surgery should be carefully determined. PMID- 2248175 TI - Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease. AB - The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system. PMID- 2248176 TI - Clinical characteristics and coronary angiographic findings of patients with unstable angina, acute myocardial infarction, and survivors of sudden ischemic death occurring during and after sport. AB - The clinical characteristics and coronary angiographic findings of 42 well conditioned subjects with an acute ischemic event related to sport are reported. Five patients had unstable angina, 25 had acute myocardial infarction (AMI), and 12 were resuscitated victims of sudden ischemic death. Twenty-two events occurred during sport (group A) and 20 after sport (group B). There were two women and 40 men. The mean age was 46 years (range 25 to 65). Twelve out of 30 patients who smoked cigarettes had an adjunctive risk factor for coronary artery disease. Twelve others (28%) had no identifiable risk factor. Prodromal cardiac symptoms were detected in three patients (group A). Two patients had previous myocardial infarction (group B). Coronary angiography was performed acutely in 39 patients. The distribution of the ischemia-related coronary artery was comparable in both groups. The lesion morphology of 35 culprit coronary arteries was described as concentric in six patients and eccentric with regular borders (type I lesion) in 11 and irregular borders (type II lesion) in 18. Eccentric lesions consistent with ruptured plaques prevailed in both groups. Associated coronary artery disease was present in 10 patients. There was no relationship between the number of risk factors and the extent of diseased coronary arteries. Clinical characteristics and coronary angiographic findings of patients with unstable angina, AMI, and sudden death either during or after sport are similar and indicate a common pathogenesis. The probable mechanism of a coronary event related to sport is exercise-induced plaque rupture. In most instances such an event is unexpected and unpredictable. Identification of some subjects at risk is possible. PMID- 2248177 TI - Effects of exercise on myocardial catecholamine content and ischemic injury in dogs with gradual coronary occlusion. AB - The effects of exercise on catecholamine content and the extent of myocardial damage in dogs with Ameroid constrictor occlusion of the left circumflex coronary artery were determined. Tissue samples from both the anterior and posterior walls of the left ventricle were obtained for determination of catecholamine content, and the rest of the ventricles were processed for histologic examination. When subjected to treadmill exercise for 40 days after surgery, obstructed animals performed significantly less exercise than sham-operated animals and showed significantly higher percentages of ischemia and necrosis in the left ventricle than sedentary, obstructed, sham-operated, or control dogs. Levels of norepinephrine and epinephrine in the posterior wall of the left ventricle were significantly lower than in the other groups. Our data show that exercise in this well-known model of chronic coronary artery stenosis produced deleterious effects on the myocardium and suggest a marked heterogeneity of catecholamine stores in the myocardium that may have important functional and electrophysiologic consequences. PMID- 2248178 TI - Clinical evaluation of high-frequency (ultrasonic) mechanical debridement in the surgical treatment of calcific aortic stenosis. AB - Repair of aortic valve stenosis due to calcific degeneration may lead to hemodynamic and clinical improvement without the problems inherent with prosthetic valves. We have evaluated the use of a device capable of debriding calcium, the Cavitron ultrasonic aspirator (CUSA), as an adjunct to mechanical debridement in the repair of calcific aortic stenosis. Ten patients (five women), ages 63 to 83 years, were studied by M-mode, two-dimensional, and Doppler echocardiography before and an average of 26 (range 3 to 124) days after this procedure. The degree of calcification of the valve cusps was clearly reduced. The maximal cusp excursion increased from 0.7 +/- 0.1 cm preoperatively to 1.5 +/ 0.4 cm postoperatively (p = 0.006). The peak aortic gradient fell from 80 +/- 36 mm Hg to 28 +/- 10 mm Hg (p = 0.0007). The mean aortic gradient fell from 53 +/- 20 mm Hg to 16 +/- 5 mm Hg (p less than 0.0001). Aortic valve area calculated by the continuity equation increased from 0.6 + 0.2 cm2 to 1.6 +/- 0.6 cm2 (p = 0.0009). No patient had more than mild aortic insufficiency preoperatively. Postoperatively, color Doppler flow mapping revealed severe aortic insufficiency in two patients. Seven patients had further echocardiographic evaluation 99 (range 33 to 196) days after the procedure. These studies revealed the development of severe aortic insufficiency in an additional four patients. Four patients with severe symptomatic aortic insufficiency eventually underwent aortic valve replacement. Pathology revealed scarring and retraction of the aortic cusps. Widening of the commissures was responsible for the severe aortic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248179 TI - Clinical and electrophysiological characteristics of ventricular tachycardia in children with normal hearts. AB - Characteristics of 18 patients with clinical ventricular tachycardia (VT) and normal hearts documented by physical examination, echocardiography, and angiocardiography were analyzed. There were 13 males and 5 females, aged 1 to 16 years (mean +/- SD, 9.7 +/- 4.8 years). Six patients had hemodynamic instability during VT and the other 12 patients were hemodynamically stable. Two patients (11%) presented with sustained VT and 16 (89%) with episodes of nonsustained VT at varying intervals (3 of 16 with repetitive monomorphic VT). Among 14 patients on whom exercise tests were performed, seven had exercise-induced VT. During electrophysiologic studies, VT was induced in 16 of 18 (89%) (in 13 patients with morphology identical to clinical VT). VT was induced by programmed stimulation (single, double, and burst stimulation of the right atrium or right ventricular apex during sinus rhythm or during pacind for eight beats) in 5 of 18 (28%) patients; with isoproterenol, VT was aggravated spontaneously in 6 of 15 (40%) patients; and during stimulation VT was induced in 8 of 15 (53%) patients. Among patients whose VT was not induced during programmed stimulation, VT was induced with the addition of isoproterenol in 11 of 12 (92%). All 14 patients in follow up are in stable condition, seven patients with medication and seven without medication. Pediatric patients with normal hearts and clinically detected VT usually have VT induced by programmed stimulation, either with or without isoproterenol stimulation. PMID- 2248180 TI - The long-term prognosis of patients with out-of-hospital cardiac arrest but no inducible ventricular tachycardia. AB - The long-term prognosis of patients successfully resuscitated from cardiac arrest who do not have acute precipitating factors and in whom ventricular arrhythmias cannot be induced during baseline electrophysiologic testing is controversial. The purpose of this investigation was to evaluate the long-term risk of recurrent sudden death and determine the clinical, angiographic, hemodynamic, and electrophysiologic predictors of recurrent cardiac arrest in such patients. Twenty-six (37%) of 71 consecutive patients with a single episode of aborted sudden death did not have inducible ventricular arrhythmias (less than 7 intraventricular responses) during baseline drug-free electrophysiologic study and they form the basis of this report. Their mean age was 54 +/- 13 (mean +/- SD) years and the left ventricular ejection fraction (LVEF) was 0.47 +/- 0.17. After a mean follow-up period of 16 months, 11 patients (42%) had a recurrent cardiac arrest (fatal in 10 patients). The actuarial incidence of recurrent cardiac arrest was 30 +/- 10% at 1 year and 55 +/- 13% at 3 years. Patients with LVEF less than or equal to 0.40 had a significantly higher occurrence of recurrent cardiac arrest than those with LVEF greater than 0.40 (p = 0.02; 1-year actuarial incidence of 57 +/- 17% versus 13 +/- 19%). Patients with recurrent sudden death had a significantly greater incidence of dilated cardiomyopathy (55% versus 7%; p = 0.02) and baseline frequent premature ventricular contractions (PVCs greater than 10/hr; 64% versus 17%, p = 0.036) or nonsustained ventricular tachycardia (36% versus 0%; p = 0.37) than patients without these characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248181 TI - Efficacy and safety of monophasic and biphasic waveform shocks using a braided endocardial defibrillation lead system. AB - Endocardial lead systems for implantable cardioverter-defibrillators utilize large (12F) rigid catheters with spring defibrillation electrodes, and lead system failure has been observed during long-term implant. We evaluated a novel flexible 8F braided electrode catheter for pacing and defibrillation in canine experiments. Active fixation and pacing were accomplished using a screw-in distal electrode, and defibrillation pulses were delivered through a braided electrode. Two braided electrode catheters were positioned in the right ventricular apex (6 cm2) and in the superior vena cava-right atrial junction (5 cm2), respectively. An elliptical 13 cm2 surface area patch electrode was positioned along the left lateral cardiac border. Ventricular fibrillation (VF) was induced and monophasic and asymmetric biphasic shocks (leading voltages 260 to 1000 V) were delivered via dual and triple electrode configurations in each animal using a prospective randomized crossover study design. Mean right ventricular pacing threshold was 0.5 +/- 0.2 mA, with a mean electrogram amplitude of 11.1 +/- 2.8 mV during sinus rhythm prior to fibrillation and defibrillation. Two hundred seven VF inductions (mean 30 +/- 4 per animal) were analyzed. The mean defibrillation threshold could be reduced to 8.0 +/- 3.2 joules with biphasic shocks from 12.9 +/- 5.1 joules obtained for monophasic shocks using a dual electrode system (p less than 0.004). Mean shock leading voltage was correspondingly reduced to 488 +/- 100 V from 691 +/- 154 V (p less than 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248182 TI - Rapid control of refractory atrial tachyarrhythmias with high-dose oral amiodarone. AB - To shorten the delay in the onset of antiarrhythmic effect when using amiodarone for the conversion of refractory atrial tachyarrhythmias to sinus rhythm, 19 patients were given oral amiodarone according to a high-dose loading protocol. In 18 of 19 patients (95%), sinus rhythm was restored 36 hours (range, 0 to 96 hours) after starting amiodarone. The conversion occurred as a result of amiodarone therapy alone within 48 hours in 12 patients (63%), and by amiodarone therapy plus electrical cardioversion at 48 to 96 hours in six patients (32%). Minor side effects were noted in eight patients (42%). No major side effects were encountered. The length of hospital stay after initiating amiodarone therapy was 3.6 days (range, 2 to 5 days). High-dose oral amiodarone loading is a safe and effective method for the rapid conversion of atrial tachyarrhythmias to sinus rhythm. PMID- 2248183 TI - Pericardial effusion in primary hypothyroidism. AB - Pericardial effusion is reported to occur in 30% to 80% of subjects with hypothyroidism. However, these earlier studies were conducted when the diagnosis of hypothyroidism was only suspected and was confirmed only in the presence of classic clinical features. In contrast, the diagnosis has recently been established in the early mild stage or more often in an asymptomatic stage because of more frequent or routine determinations of thyroid function tests, especially in the elderly. Thus the subjects in the older studies were severely hypothyroid at the time of diagnosis and may not be representative of the present hypothyroid population. For this reason, 30 subjects with hypothyroidism were evaluated with echocardiography to reassess the evidence of pericardial effusion in this disorder. Only two subjects demonstrated pericardial effusion, and in only one of them with severe disease could the pericardial effusion be attributed to hypothyroidism, since it resolved on the patient's attaining the euthyroid state. Thus the incidence of pericardial effusion was only 3% to 6%, depending on the inclusion of one or both subjects, an extremely infrequent occurrence when compared with that of previous studies. Moreover, the occurrence of pericardial effusion in hypothyroidism appears to be dependent on the severity of the disease. Thus pericardial effusion may be a frequent manifestation in myxedema, an advanced severe stage, as previously found, but a rare association of hypothyroidism, an early mild stage, because of the timeliness with which the latter condition is nowadays detected. PMID- 2248184 TI - Effect of machine parameters on variance display in Doppler color flow mapping. AB - In color Doppler flow studies, "variance" is an important display modality for diagnosing stenotic, regurgitant, and shunt lesions. Variance, a mathematical calculation based on the variation in the Doppler signal frequencies, has been reported to reflect the degree of flow disturbance. A wide-band pulsed Doppler spectrum results in a larger degree of variance. It has been suggested that variance area (green color or mosaic area) might provide useful quantitative information regarding the severity of stenotic, regurgitant, and shunt lesions. Since ultrasound machine settings may affect the color Doppler variance image, we evaluated in 101 free jet experiments the effect of packet size (eight versus four samples per line), pulse repetition frequency (3.9 versus 5.2 kHz), frame rate (11 versus 22 frames per second), system gain (+15 dB versus -15 dB), transmit power (high versus low), and moving target indicator (MTI) filter setting (high versus low) on variance display. The variance area was planimetered using an image analysis computer. The following machine parameters were inversely correlated with variance area: (1) packet size (p less than 0.01), (2) pulse repetition frequency (p less than 0.001), and (3) frame rate (p less than 0.05). Both system gain (p less than 0.001) and wall filter setting (p less than 0.01) showed a direct correlation with variance area. We conclude that machine factors must be standardized in evaluating stenotic, regurgitant, and shunt lesions by color Doppler variance display imaging. PMID- 2248185 TI - Cocaine-induced heart diseases. PMID- 2248186 TI - New calcium antagonists: relevance of vasoselectivity. AB - The calcium antagonists are a heterogeneous class of drugs used to treat a number of cardiovascular disorders. A new generation of calcium antagonists under development have a higher degree of selectivity for vascular smooth muscle and coronary vasculature compared with verapamil, nifedipine, and diltiazem. The clinical relevance of vasoselectivity and its impact on drug selection are discussed. The newer calcium antagonists are important alternatives to older agents and may be associated with improved tolerance and a reduced incidence of adverse effects. Their place in therapy has yet to be defined by comparative studies of efficacy and safety. PMID- 2248187 TI - Peripheral arterial occlusive disease of the extremities in the United States: hospitalization and mortality. AB - PAODE is an important cause of morbidity and health care expenditures among the elderly. Data from the NHDS and National Vital Statistics System were used to assess its impact in the U.S. In 1985 to 1987, an estimated 229 thousand men and 184 thousand women per year were discharged with any diagnosis of chronic PAODE. Discharge rates were much higher in men and increased sharply with age. Lower extremity arteriography was performed during 88 thousand hospitalizations and aorta-iliac-femoral bypass procedures were done during 31 thousand hospitalizations per year. Numbers of procedures increased markedly since 1979. An estimated 60 thousand men and 50 thousand women per year were discharged with any diagnosis of acute PAODE. Embolectomy or thrombectomy of lower limb arteries was listed for 28 thousand discharges per year. Few deaths were attributed to PAODE. Although these data are limited by likely incomplete reporting and by the nonspecificity of diagnostic codes, they provide an indication of the magnitude of the problem. An aging population and advances in surgical techniques suggest continued monitoring using multiple data sources. Vigorous primary prevention programs are needed to lessen the impact of all atherosclerotic diseases. PMID- 2248188 TI - Fascinating rhythm: a primer on chaos theory and its application to cardiology. AB - Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible. PMID- 2248189 TI - Transcatheter coil closure of a congenital coronary arterial fistula. PMID- 2248190 TI - Early thromboxane release during pacing-induced myocardial ischemia with angiographically normal coronary arteries. PMID- 2248191 TI - Hyperventilation testing for coronary vasospasm: induction of spontaneous ventricular tachycardia in association with transmural ischemia without obstructive coronary disease. PMID- 2248192 TI - Transient myocardial wall motion abnormalities in a child: the phenomenon of "stunning". PMID- 2248193 TI - Coronary artery spasm induced by anaphylactoid reaction to a new low osmolar contrast medium. PMID- 2248194 TI - Fatal intrapericardial rupture of sinus of Valsalva aneurysm. PMID- 2248195 TI - Transesophageal echocardiographic diagnosis of recurrent right ventricular myxoma 2 years after excision of right atrial myxoma. PMID- 2248196 TI - Primary cardiac rhabdomyosarcoma exhibiting transient and pronounced regression with chemotherapy. PMID- 2248197 TI - Cardiovascular findings in alkaptonuric ochronosis. PMID- 2248198 TI - Free-floating ball thrombus in left atrium after mitral valve replacement: surgical removal following embolization to the aorta. PMID- 2248199 TI - Delayed presentation of cardiac perforation after apparently successful catheter ablation for incessant ventricular tachycardia. PMID- 2248200 TI - Cardiac tamponade in the acquired immunodeficiency syndrome. PMID- 2248201 TI - Arrhythmogenic potential and histopathologic effects of transluminal endomyocardial laser ablation. PMID- 2248202 TI - Preexcited tachycardia due to atrioventricular node reentry with a bystander accessory pathway diagnosed after procainamide infusion. PMID- 2248203 TI - Malignant pericardial effusion. PMID- 2248204 TI - Diltiazem-carbamazepine interaction. PMID- 2248205 TI - Balloon valvotomy. PMID- 2248206 TI - One-year TIMI II pilot results. PMID- 2248207 TI - Appraisal of clinical models based on results of stress nuclear imaging in risk stratification. PMID- 2248208 TI - Prevention of bacterial endocarditis in patients with permanent pacemakers and automatic internal cardioverter defibrillators. PMID- 2248209 TI - Epidemiologic aspects of heart failure. AB - The prevalence of heart failure in Northwest London is 0.4%, a lower figure than that quoted for the United States. Heart failure is a common reason (5%) for medical admission to the hospital in the London area. The problem of heart failure is predominantly in persons over 65 years. Coronary artery disease is the most frequent cause, and hypertension is relatively uncommon. In those patients admitted to the hospital, the prognosis is poor. PMID- 2248210 TI - Can heart failure be prevented, delayed, or reversed? AB - A review of the clinical course of chronic heart failure demonstrates that current outcomes remain highly unsatisfactory both in mortality and perhaps more important in morbidity. The extraordinary satisfactory functional responses seen in patients who undergo cardiac transplantation clearly identify the primary cause as the status of the heart itself, whatever the pathophysiologic adjustments of the neuroendocrine system, and interventions of the wide variety of drugs. Since donor hearts are unlikely to be available even from younger sufferers of these clinical syndromes, prevention must be the hallmark. Protection of the viability of myocytes, such as in acute myocarditis and acute infarction, is essential. Myocardial collagen undergoes continual synthesis, and production is greatly stimulated in the presence of hypertrophy caused by increased wall stress. It is possible that excess collagen is intimately involved with diastolic ventricular dysfunction, but that this may be a reversible process if the collagen-producing stimulus is removed. Thus reduction in wall stress and reversibility of ventricular hypertrophy appear to be promising directions. However, to limit the catastrophic effects of chronic heart failure, early recognition of the precursors of these syndromes, prevention of progression, and surgical intervention in valvular heart disease at an optimal point in time are essential. PMID- 2248211 TI - Regional blood flow supply and demand in heart failure. AB - Heart failure results not only in a fall in cardiac output but also in a redistribution of blood flow favoring some regional beds (the brain and the heart) at the expense of others (the kidney and working skeletal muscle). The chronic resting hypoperfusion of striated muscle is further compromised with exercise. Maladaptive vasoconstrictor control mechanisms prevent the redirection of blood flow from nonworking muscle and liver to working muscle. This inappropriate preservation of nonworking organ perfusion further compromises the functional capacity of working muscle and is associated with evidence for metabolic deconditioning with reduced oxygen extraction and impaired oxidative phosphorylation. It is becoming increasingly clear that the clinical response to the inotropic and vasodilator therapy used in heart failure is in part dependent on the differing regional blood flow profiles of the various agents studied. The ability of the angiotensin-converting enzyme inhibitors to redirect blood flow away from nonworking regional beds to exercising muscle, and thereby to reestablish an appropriate physiologic response to changing metabolic needs, may be the overriding reason for their long-term efficacy. Certainly in the future the comprehensive therapy of heart failure will have to take into consideration not only central hemodynamic but also regional blood flow/supply and demand issues. PMID- 2248212 TI - Compensation and overcompensation in congestive heart failure. AB - The compensatory mechanisms that develop in response to heart failure have been well defined. In this review, it is argued that each compensatory mechanism leads to overcompensation and that there is no way to distinguish between the beneficial aspects of the former and the harmful effects of the latter. Therapeutic agents that maintain rather than decrease blood pressure might perhaps be more beneficial because of the crucial role of hypotension in initiating both compensation and overcompensation. PMID- 2248213 TI - Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. AB - In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha 2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous "down-regulation" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta 2 ARs are nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248214 TI - How to select a drug for the long-term treatment of chronic heart failure. AB - First-line drugs for the treatment of chronic congestive heart failure should produce immediate symptomatic benefit, improve exercise tolerance, and thereby improve the quality of life. They should preferentially be active as monotherapy or at least reduce the need for comedication. The drugs must be safe and well tolerated by patients and change, in the end, the natural history of the disease, so that sudden death will be prevented and life expectancy improves. None of the currently available drugs satisfies all these criteria. Diuretics, digitalis, converting-enzyme inhibitors, and ibopamine come close to the described ideal. PMID- 2248215 TI - The placebo effect in heart failure. AB - Many patients who are enrolled in controlled clinical trials of new drugs for the treatment of heart failure show favorable hemodynamic and clinical responses to placebo therapy. This "placebo effect" results from both the creation of a supportive therapeutic environment and the spontaneous improvement that is commonly seen when measurements of symptoms and cardiac function are repeated frequently over long intervals of time. Three months of treatment with a placebo produces a reduction in symptoms in 25% to 35% of patients, an increase in cardiac output and a decrease in pulmonary wedge pressure, and an increase in exercise tolerance of up to 90 to 120 seconds. Physicians commonly seek to maximize the "placebo effect," since the goal of treatment in the clinical setting is to improve the quality of the patient's life. On the other hand, clinical investigators seek to minimize the "placebo effect," since the goal of a research study is to test the hypothesis that the new drug is superior to a placebo. PMID- 2248216 TI - The ischemic myocardium: new directions in evaluation and management. November 12, 1989, New Orleans, Louisiana. Proceedings. PMID- 2248217 TI - Role of echocardiography in acute myocardial infarction. AB - Interventional therapies such as thrombolytic agents, angioplasty and surgery have emerged as important options in the management of patients with myocardial infarction. These therapies are aimed at improving myocardial perfusion with the ultimate improvement or restoration of myocardial function. Two-dimensional echocardiography with digital storage and display is an ideal technique for temporally monitoring regional ventricular function and the effectiveness of interventional therapy. By design, 2-dimensional echocardiography is noninvasive and can be performed conveniently at the bedside. For these reasons, echocardiography is the principal imaging technique at Indiana University Hospital for patients with acute myocardial infarction. Computer retrieval of echocardiograms can be achieved in about 10 seconds at the nurses' station in the coronary care unit. With the availability of such an examination, the physician has a better understanding of the site, size and function of the infarct area. The state of the noninfarcted myocardium is also assessed and may be critical to the patient's prognosis. With the digital recordings, serial studies can be displayed side-by-side, making it easier for the physician to follow the natural history or to judge the effect of therapy. Echocardiography also is useful in identifying many complications that can occur with myocardial infarction. For these reasons, and because echocardiography will also show related cardiac problems, it is indispensable in the management of acute myocardial infarction. PMID- 2248218 TI - A new generation of calcium antagonists and their role in atherosclerosis. AB - A new generation of calcium antagonists is being developed in an attempt to improve the already widespread therapeutic applications of this class of drugs. In this report the effect of these new calcium antagonists on those processes involved in atherogenesis that occur in the cellular component of the arterial wall is reviewed. The new generation of calcium antagonists appears to possess many of the antiatherosclerotic properties demonstrated by their prototypes. Moreover, these new compounds may have unique mechanisms of action and may be more potent than their first-generation counterparts. PMID- 2248219 TI - Robert N. Hicks receives CAO distinguished service award. PMID- 2248220 TI - Response to Clark's comments in March issue. PMID- 2248221 TI - The bandless bracket attachment. PMID- 2248222 TI - Comments on Class II, division 2 malocclusion. PMID- 2248223 TI - A further word on straight wire appliances. PMID- 2248224 TI - Effect of orthodontic bands on microbiologic and clinical parameters. PMID- 2248225 TI - Mandibular advancement and reduction genioplasty. AB - This case report is presented in accordance with the specifications of the American Board of Orthodontics. Before treatment, the patient had a unilateral transverse discrepancy and dentoskeletal Class II malocclusion. Clinically, however, the profile was acceptable. She was treated with an orthodontic and orthognathic surgical approach. Interesting treatment-planning considerations included the existence of an eight-unit bridge and incisor periapical pathosis. PMID- 2248226 TI - Auxiliary springs in continuous arch treatment: Part 2. Appliance use and case reports. AB - In the second part of this series, three clinical examples are presented to illustrate the use of auxiliary space-closure springs with clinically manageable moment-to-force ratios and new canine brackets to accommodate these springs within the framework of conventional and straight-wire 0.018-inch appliance systems. Eligiloy retraction spring models (0.1650 inch x 0.02150 inch) in the edgewise mode were developed for translational movements along a main archwire. The effects of different preactivation bends for influencing intraarch anchorage are shown for the conditions of reciprocal closure, posterior protraction, and anterior retraction. PMID- 2248227 TI - Evaluation of friction between ceramic brackets and orthodontic wires of four alloys. AB - The purpose of this investigation was to determine the frictional resistance offered by ceramic brackets used in combination with wires of different alloys and sizes during in vitro translatory displacement of brackets. Findings with ceramic brackets were also compared with outcomes of treatment with stainless steel brackets. Stainless steel, cobalt-chromium, beta-titanium, and nickel titanium wires of different cross-sectional sizes were tested in medium-twin monocrystalline ceramic brackets with both 0.018-inch and 0.022-inch slot sizes. The wires were ligated into the brackets with elastomeric modules. Brackets were moved along the wire by means of an Instron universal testing machine, and frictional force was measured by a compression cell and recorded graphically on an xy recorder. Wire friction in the ceramic brackets increased as wire size increased, and rectangular wires produced greater friction than round wires. Beta titanium and nickel-titanium wires were associated with higher frictional forces than stainless steel or cobalt-chromium wires. These findings follow the same general trends as those found with stainless steel brackets; however, wires in ceramic brackets generated significantly stronger frictional force than did wires in stainless steel brackets. PMID- 2248228 TI - Swallowing patterns in human subjects with and without temporomandibular dysfunction. AB - Recent clinical impressions have suggested that tongue-thrust swallowing may often occur in patients with internal derangement of the temporomandibular joint(s) and may represent an unconscious effort to avoid temporomandibular joint (TMJ) dysfunction by minimizing noxious stimuli from the joints. The purpose of this study, therefore, was to determine the swallowing patterns in human subjects with and without TMJ dysfunction. The swallowing patterns of 25 adult orthodontic patients already known to have TMJ dysfunction and 25 adult control subjects without such dysfunction were examined with the aid of kinesiographic and electromyographic recordings taken while the subjects were sipping water. Analysis of the data revealed that 19 patients with TMJ dysfunction used a tongue thrust open-jaw swallowing pattern, while only nine control subjects used such a swallowing pattern. Furthermore, six of the patients with TMJ dysfunction had an anterior open bite, while none of the control subjects had an anterior open bite. The results suggest that patients with aberrant swallowing patterns should be examined for temporomandibular joint dysfunction. PMID- 2248229 TI - TMJ sounds: are they a common finding or are they indicative of pathosis/dysfunction? PMID- 2248230 TI - Increased overbite and craniomandibular disorders--a clinical approach. AB - This study investigated the effect of a maxillary fixed lingual arch with anterior bite plane on adult patients with craniomandibular disorders (CMD) and increased overbite. The sample comprised 11 patients with an increased overbite (greater than 5 mm) and a normal or Class II molar relationship. The main CMD symptoms were daily tension headache in the region of anterior temporal muscles and/or pain or clicking in the temporomandibular joint. Previous treatment with stabilization splints, removal bite plates, or occlusal grinding had not given satisfactory results. When the maxillary lingual arch with anterior bite plane was fitted, molar separation was approximately 4 mm, and occlusal contact occurred only between the acrylic bite plane and the lower six anterior teeth. The permanent appliance could be removed only by the orthodontist. All patients reported relief of CMD symptoms 1 to 2 weeks after initiation of treatment. After a mean time of 3 months, a flatter curve of Spee, molar contact, and reduced overbite could be seen in all cases. The excessive overbite had decreased approximately 3.4 mm. Subsequent treatment involved orthodontic or prosthetic therapy to normalize and stabilize the sagittal and vertical dimensions. After an average posttreatment observation period of 2 years, all patients remained free of CMD pain. PMID- 2248231 TI - A quantitative assessment of respiratory patterns and their effects on dentofacial development. AB - The purpose of this study was to assess the effects of quantitatively determined breathing patterns on dentofacial development in growing children. Forty-nine subjects ranging in age from 10 to 16 years participated in the breathing pattern assessment portion of this project. Oral, nasal, and total airflow were measured at separate times by means of a head-out body plethysmograph technique and the values were compared with the subjects' and parents' subjective perceptions of their breathing modes. These breathing pattern measurements also were compared to nasal airway resistance and nasal power. Temporal variation and cyclic respiration, which may play important roles in quantitative evaluations of childrens' breathing patterns, also were addressed. In addition, objective assessments of possible associations between dentofacial structure and respiration were made on 45 of these children. Most subjects' exhibited was either an oronasal or a completely nasal respiratory pattern. However, significant variation in breathing measures was evident among a number of subjects whose breathing was measured twice on the same day and on different days. No significant correlations were found between objectively measured and subjectively determined impressions of respiratory patterns. In addition, there was no association between nasal airway resistance or nasal power and plethysmograph recordings of percent of mouth breathing. Comparisons of measured breathing modes and dentofacial characteristics revealed a weak tendency among mouth breathers toward a Class II skeletal pattern and retroclination of maxillary and mandibular incisors. In contrast, subjective perception of mouth breathing was associated with increased anterior facial height and greater mandibular plane angles. Nasal power and resistance were not correlated with either dental or skeletal variables. This study presents evidence that determination of respiratory pattern is a complex issue for which methods must be refined and performed longitudinally. PMID- 2248232 TI - The effects of orthodontic forces on the mechanical properties of the periodontal ligament in the rat maxillary molars. AB - Previous studies have shown that the mechanical strength of the periodontal ligament decreased markedly after the application of an orthodontic force to the rat mandibular first molar. However, the effects of orthodontic forces on the mechanical properties of the periodontal ligament of the other teeth in the same dental arch have not been examined. Furthermore, a detailed analysis of the mechanical parameters has not been made. The purpose of the present study was to analyze mechanical parameters such as maximum shear load, maximum deformation, elastic stiffness, and failure energy in shear, estimated from the load deformation curves obtained by extracting the rat maxillary molars from their sockets after application of an orthodontic force for 5 days. It was found that the mechanical properties of the periodontal ligament of the rat maxillary molars varied considerably among control teeth in the same dental arch. Decreases in the mechanical properties of the periodontal ligament of the experimental teeth were greatest in the first, less in the second, and least in the third molars. Significant correlations were found between the maximum load and the failure energy and between the maximum deformation and the failure energy in all teeth. It was concluded that orthodontic force affected not only the mechanical properties of the periodontal ligament of the teeth to which the force had been applied but also the mechanical properties of distant teeth. PMID- 2248233 TI - The effect of bite-opening appliances on mandibular rotational growth and remodeling in the rhesus monkey (Macaca mulatta). AB - Previous experimental studies that have used a bite-block cemented to the maxillary dental arch have shown that the direction of growth of the maxillary complex is redirected in a superior and anterior direction for approximately 12 weeks but reassumes a normal inferior and anterior direction after that time. The purposes of this study were (1) to examine the effect of increased vertical dimension and altered mandibular posture on growth of the mandible and (2) to determine whether or not an alteration in chronic mandibular position alters mandibular intramatrix rotation. Eleven Macaca mulatta monkeys wore 15 mm vertical bite-opening appliances for 24 or 48 weeks. Nine untreated animals were used as controls. All animals received tantalum bone implants to facilitate cephalometric analysis. Serial lateral radiographs of the mandible were traced and superimposed on bone implants for each animal to determine overall changes in mandibular shape (gonial angle) and the location of bone remodeling. During normal growth, the gonial angle closed an average of 0.1 degrees over a 48-week period. In the experimental animals, the gonial angle opened 6.4 degrees (p less than 0.005) as a result of remodeling during the period that mandibular posture was altered. Once normal mandibular posture was restored, this process was reversed; the gonial angle once again became more acute over time, and remodeling along the body and ramus of the mandible was similar to that observed in control animals. These results suggest that mandibular growth and remodeling can be influenced by altered mandibular vertical posture. PMID- 2248234 TI - Assessing treatment effectiveness of removable and fixed orthodontic appliances with the occlusal index. AB - Orthodontists from different backgrounds may have different opinions about removable and fixed orthodontic appliances, but there have been few objective comparisons of their relative treatment effectiveness. It is the purpose of the present study to analyze objectively the effectiveness of these two types of appliances. Eighty cases involving patients who had been treated with removable appliances and 67 cases of patients treated with fixed appliances were studied with respect to the Occlusal Index (OI). Scores indicating severity of malocclusion were obtained from pretreatment and posttreatment study casts. The effectiveness of the fixed appliance (represented by average reduction in OI score) was much greater than that of the removable appliance. The result of treatment with the fixed appliance was also found to be much better than that of the treatment with the removable appliance (indicated by the much lower posttreatment OI score in the fixed-appliance cases). The Occlusal Index was designed to measure features of basic malocclusion and is not a very sensitive index for assessing symptoms of a developing malocclusion. The fact that both the treatment effectiveness and the treatment results of the removable appliance were found to be inferior to those of the fixed appliance may indicate that the removable appliance has been used largely to correct "symptoms" rather than basic malocclusion. PMID- 2248235 TI - Legal aspects of orthodontic practice: risk management concepts. A tale of two splints. PMID- 2248236 TI - Farmers' occupational health care--worldwide. AB - This review will summarize the current state of preventive health care systems for farmers in the world. It is obvious that well-organized occupational health care systems for farmers occur sporadically in only a few countries, and generally are in the initial stages of development. Large cooperative farms and plantations may have industrialized occupational health care. In some countries in Europe, e.g., France and Austria, farmers' organizations may include a certain amount of health and safety activity within their social insurance systems for farmers. Moreso than in other places, the Scandinavian countries have tried different approaches to provide comprehensive health services among farmers. Regardless of the kind of system, it is obvious from experiences worldwide that agriculture is a risky occupation and farmers are exposed to numerous hazards which may result in injuries, work-related diseases, and death. It is promising to note an increased interest in this situation from many parts of the world. PMID- 2248237 TI - Farmers' health and safety programs in Sweden. AB - In 1977, the Swedish Farmers' Federation initiated a pilot project of preventive occupational health services to farmers. After a few years it was decided that this occupation-specific service, Farmers' Preventive Health Service (Lantbrukshalsan), should be permanently established within the federation of farmers. Today, 33 special regional centers have been established around Sweden, providing occupational health services to farmers, farm workers, and others occupied in farm-related enterprises. At another 30 locations collaboration has been established with other existing health care centers. Farmers must pay a fee to become a member of the organization and to provide affiliation is voluntary. Today about 40,000 farmers are members. The main goal of the farmers' preventive health service (FPHS) is to prevent work-related injuries and illnesses and to provide clinical services to farmers for occupational medical problems. Every second year a health check-up is performed; during the years in between other services such as farm visits, first aid courses, and sessions on prevention/amelioration of back and neck problems are provided. A team of occupational nurses, physiotherapists, agricultural safety engineers, doctors, and secretaries work together to provide comprehensive services. This integrated medical-technical approach to service provision is a prerequisite to successful intervention for the many occupational hazards which may cause damage to health. Respiratory problems related to inhalation of organic dust, pesticide exposures, allergies, and orthopedic diseases are important. Psychosocial work-related problems seem to be increasing among farmers. PMID- 2248238 TI - Farmers' occupational health program in Finland, 1979-1988: from research to practice. AB - The Kuopio Regional Institute of Occupational Health, in collaboration with the Social Insurance Institution and the National Board of Health, conducted and evaluated a national model for the farmers' occupational health services. In January 1985 the National Board of Health instructed the Finnish municipal health centers to start the provision of farmers' occupational health services based on the recommendation given by the research group. The service was evaluated by experiments carried out during 1982, 1985, and 1986. The main problem in function of the services was that the health hazards (exposures) were difficult to observe and evaluate. The system of how the occupational health nurse evaluates the working conditions should be further developed. The efficiency of the services was studied by postal inquiries in 1982 and 1986. Farmers' knowledge about the appropriate means of reducing hazardous exposures had increased significantly due to the occupational health services. At the local level, the main problem in providing services for occupational farmers is that health centers do not have the resources to offer services for all farmers at the same time. Altogether by the end of 1986, about 30% of all active farmers in Finland (45,000 farmers) were willing to have occupational health services, which is voluntary for self employed farmers. PMID- 2248239 TI - Iowa Agricultural Health and Safety Service Project. AB - A model community-based comprehensive agricultural occupational health and safety service program has been implemented in Iowa. The functional center of coordination is based in the College of Medicine at the University of Iowa. The community-based hub of the service is the community hospital, where the majority of the direct client services originate. The University provides training of hospital staff, programming, direction, consultation, and referral. The services offered include primary care, health surveillance, industrial hygiene and safety, and education. Through a detailed evaluation of the project's objectives we will be able to evaluate, modify, and disseminate a model agricultural health and safety services delivery program. This model should be effective in changing the farming population's health and safety attitudes and behaviors through a community-based program. PMID- 2248240 TI - The Bassett Farm Safety and Health Project. AB - The Bassett Farm Safety and Health Project was started in 1980 when Drs. May and Pratt made clinical observations on respiratory illnesses in farmers. The initial work involved the investigation of clinical syndromes associated with dust exposures and, from there, environmental dust studies. The current scope of work of The Farm Safety and Health Project includes three major components: research, education, and patient care. The research activities currently include studies into the analysis of injuries on farms, hearing loss in a randomly selected population, and estimating the annual incidence of Silo Filler's Disease in New York State. Educational activities currently include a statewide hearing conservation project, and the provision of numerous education materials for farmers and farm workers. The clinical activities include the establishment of an occupational medicine clinic in the fall of 1988, designed specifically for evaluation and treatment of agricultural workers with occupation-related illness and injuries. PMID- 2248241 TI - Reaching the difficult audience: an experiment to provide occupational health services to farmers and ranchers in Colorado, U.S.A. AB - From its inception in the late 1970s, the W.K. Kellogg Foundation funded Workplace Health in Agriculture Program at Colorado State University underwent numerous evolutions as the needs of the agricultural community were identified. Direct health and safety consultation with agribusiness met with limited success due to the cost of providing services over a wide geographic area and a general unwillingness within this group of employers to involve themselves with "OSHA" type regulations. Therefore, the program changed from promotion of, and providing health and safety consultation upon request, to education of specific target groups within the agricultural community supplemented by consultation services when needs were identified. Target groups for educational services included rural health care providers, vocational-agriculture students and teachers, farm/ranch clubs and groups (with special emphasis on farm wives groups), and rural emergency services. These groups became the promoters of health and safety within the agriculture community, which resulted in a direct, positive impact on requests for, and interest in health and safety services provided by the program. PMID- 2248242 TI - Practice-based agromedicine: the need for client-centered research. AB - During recent years, several client calls received from Clemson University Cooperative Extension Service office and private physicians have required client oriented investigations. These have practical implications for preventive medicine and public service. The challenges for differential diagnosis across disciplines are not for the faint-of-heart or the narrow thinking specialist. Examples of incidents that have signaled a problem and resulting research projects are: 1) anaphylactic cardiovascular response to red imported fire ant venom (statewide morbidity survey); (2) unexplained contact dermatitis in tomato harvesters and floral designers (immunodermatologic study and statewide survey of florists); (3) concerns over two unexplained cancer deaths at an experimental agricultural research station (farmer's mortality study); (4) a household outbreak of organophosphate poisoning (statewide hospital morbidity survey); and (5) a woman in early pregnancy exposed to misapplication of chlordane in her house (literature review and update on trends in U.S. birth defects). These examples reflect a broad but responsive interdisciplinary approach to the needs of the clients of the South Carolina Agromedicine Program. PMID- 2248243 TI - Safety programs of the Farm Safety Association in Ontario, Canada. AB - The Ontario Farm Safety Association, established in 1973 under the Workers' Compensation Act, provides safety education services to the agricultural community to reduce injuries and fatalities. With a staff of 14, various programs are administered including health and safety seminars, inspections, technical consulting, specialized agricultural safety publications and audio-visual materials, statistical gathering and analysis, as well as elementary school programs. PMID- 2248244 TI - A case for medical, environmental, and safety screening. AB - Agriculture is one of the most hazardous occupations in the United States, yet there has been no improvement noted over the past 30 years. While occupational health and safety improvements have been noted in other industrial sections, agriculture continues to pose many unusual health threats to the farmer. Screening programs are fraught with many problems in view of the widely dispersed nature of agriculture. Pulmonary function studies, dust levels, serological testing, hearing testing and noise level production, and cholinesterase levels are but a few of the tools that are available, and are helpful in looking for problems in this most vital industry in the United States. PMID- 2248245 TI - Physicians as the weak link in agricultural health services: defining the agenda for action. PMID- 2248246 TI - The farm family perception of occupational health: a multistate survey of knowledge, attitudes, behaviors, and ideas. AB - It is vitally important to integrate the views and concerns of the farm family into the process of policy development. If the input is not there, policy planners could implement programs that are philosophically separated from the farm families' concerns and attitudes. This would destroy credibility and future farmer support of any new program development. From May of 1988 to April of 1989, a phone and mail survey of approximately 1,500 farmers and spouses was conducted to assess knowledge, attitudes, and behaviors regarding agricultural safety and health. The survey was conducted in Iowa, New York, South Carolina, and Washington state. Preliminary results from Iowa and New York indicated that: 1) farmers value highly, and are concerned with, occupational health and safety issues; 2) farmers report that their major concerns include stress, trauma and respiratory problems; 3) farmers would like access to an occupational health and safety service; and 4) any new farm health and safety programs must include farmer input to ensure practicality, applicability, and acceptance. PMID- 2248247 TI - Rural hospitals and the provision of agricultural occupational health and safety services. AB - Agriculture is one of the most dangerous work environments in the United States. Ironically, there is a near-total absence of occupational health and safety services being provided to agricultural workers. While many of the agricultural occupational hazards could be addressed through health and safety services provided by rural hospitals, the absence of dedicated funds to pay for these services is a major barrier. The ability of rural hospitals to provide these services and specific issues related to the unique character and problems in implementing agricultural occupational health and safety services are discussed. PMID- 2248248 TI - A case for social marketing and education for acceptance and implementation of preventive health and occupational safety measure programs for rural communities. AB - The environment in which acceptance and implementation of preventive health and occupational safety occurs is not conducive to the message being heard, nor are people acting upon the message. Diffusion of innovation and community development models are explored for possible approaches to health education in the rural community. In particular, the community-oriented primary care approach to medical practice is discussed. In addition, the responsibility of the rural community is outlined. PMID- 2248249 TI - Continuing importance of nitrate contamination of groundwater and wells in rural areas. AB - The contamination of groundwater and rural drinking water supplies by nitrates from livestock and human excrement, other organic waste, or chemical fertilizers is a potential hazard throughout the world. Infant illness and death from nitrate induced methemoglobinemia is probably often misdiagnosed, perhaps as sudden infant death syndrome, and certainly contributes to the national infant death rate statistics. A 1950 report listed 144 cases of infant methemoglobinemia with 14 deaths in one 30-month period in Minnesota. Infant deaths resulting from misdiagnosis of this preventable, treatable intoxication were still occurring as recently as 1986 in South Dakota. In this state, about 39% of dug or bored wells were unsafe due to high nitrate content, compared with 22% of drilled wells and 16% of driven wells. Properly constructed wells more than 30 m deep are more likely to be safe. Groundwater concentrations of nitrate may be unsafe for consumption, and standards are needed to regulate such contamination. Such standards could serve as guidelines and could be enforceable in the case of water systems dependent on wells. PMID- 2248250 TI - Pesticide loss to the atmosphere. AB - Pesticides may be transformed by chemical and biological processes or transported from the site of application by several processes including runoff, movement through the soil to ground water, volatilization, transport on soil particles, and wind erosion. Contamination of water by pesticide residues is a matter of concern as is contamination of the earth's atmosphere. The form in which a pesticide enters the air and the dimensions of pesticide-containing particulate matter affect movement and deposition. Local transport over distances of several miles may be responsible for adverse effects on nontarget species. Effects of long-range transport are more difficult to assess, but pesticides increase the burden of organic chemicals in the atmosphere. Field measurements of pesticide volatilization and deposition of residues in rainfall, particulate matter, fog, etc., provide information on the relative importance of these processes. Adequate information concerning chemical reactions of pesticides in air is lacking. Because it is desirable to minimize low-level human and environmental exposure resulting from airborne pesticide residues, potential for losses to the air should be taken into account in selecting pesticide formulations and application methods. PMID- 2248251 TI - Some issues in risk assessment for agricultural chemicals. AB - Risk assessment is now a significant feature of most environmental risk management programs, in both industry and government. The purpose of this paper is to describe the elements of risk assessment, their strengths and limitations, and their relationship to other activities, including research and risk management. Risk assessment issues to be examined are those especially important to the agricultural community, including problems of high-risk subpopulations, exposure through unauthorized pathways (e.g., those resulting from groundwater contamination or pesticide misuse), and inadequacies in toxicity and residue data bases. PMID- 2248252 TI - Agricultural chemical application practices to reduce environmental contamination. AB - Current practices of applying agricultural chemicals play a major role in the environmental health concerns of agriculture. Those who mix, load, and handle the concentrated formulations run the greatest risk of exposure but field hands and others can encounter significant levels of pesticides. Drift can be a major source of contamination to residents, wildlife, and water sources. Improved methods of application and ways of reducing the total amount of pesticide applied can help reduce environmental contamination. Chemigation, direct injection, closed system handling, and fertilizer impregnation are examples of technology that affect the efficiency of applying agricultural chemicals. An area of beneficial research is related to leak and spill technology. Current surveys indicate that point sources such as spills, mixing and loading areas, back siphoning, and direct routes for surface water movement into the ground are often a major cause of pesticides reaching groundwater. The commercial dealer/applicator provides storage, handling, mixing, and loading for large amounts of chemicals and has received limited guidance regarding the products. Education remains an important element of any rural environmental health strategy. With appropriate information about pesticide risks and groundwater, people will be better equipped to address environmental concerns. By design, agricultural chemicals are biologically active and, in most cases, toxic. Thus, they pose potential risks to humans, wildlife, water, and the environment in general. The magnitude of the risks depends to some degree on the methods and techniques used to apply the chemicals. Pesticides are applied by persons possessing a variety of skills, using equipment ranging from hand-operated systems to aircraft. PMID- 2248253 TI - California's Proposition 65: extrapolating animal toxicity to humans. AB - In 1986, the voters of California passed a law regarding the concept of extrapolating animal toxicity data to humans. The California Safe Drinking Water and Toxic Enforcement Act of 1986, known as Proposition 65, does five things: 1. It creates a list of chemicals (including a number of agricultural chemicals) known to cause cancer or reproductive toxicity; 2. It limits discharges of listed chemicals to drinking water sources; 3. It requires prior warning before exposure to listed chemicals by anyone in the course of doing business; 4. It creates a list of chemicals requiring testing for carcinogenicity or reproductive toxicity; and 5. It requires the Governor to consult with qualified experts (a 12-member "Scientific Advisory Panel" was appointed) as necessary to carry out his duties. This paper discusses the details and implications of this proposition. Areas of responsibility have been assigned. The definition of significant risk is being addressed. PMID- 2248254 TI - Food production, environmental protection, and health effects in Mexican agriculture. AB - In countries like Mexico, where the need to increase agricultural productivity to satisfy an ever-increasing population is great, attention to environmental problems is recent. However, current public concern has forced the administration to consider environmental protection as a key strategy in the development model. The purpose of this paper is to present the efforts being made by the country, the state of research, legislation, and regulations, and the level of participation by agrichemical producers in aiming to balance protection of the environment and development in the agricultural sector, including intensive use of mechanization and agrichemicals. PMID- 2248255 TI - Current trends and new directions in crop protection. AB - Synthetic agricultural chemicals will continue to be the major component in protecting food and fiber crops from attack by insects, fungi, and weeds. This trend will most likely continue through the end of this century and possibly beyond. The discovery and introduction of potent new pesticides such as the sulfonylurea and imidazolinone herbicides and synthetic pyrethroid insecticides have demonstrated that excellent weed and insect control can be achieved with minute amounts of chemical per treated unit area in comparison to older chemicals. In some instances, these reductions approached two orders of magnitude. Further improvements in delivery systems and formulations have also contributed to reductions in the chemical load in the environment. However, increased regulatory demands; environmental concerns; developing resistance in key pests; increasing costs of research, development, manufacturing, and selling; and even a smaller number of basic producers, all in concert impact heavily on future developments in chemical pesticides. We can expect also that, within the next decade, there will be an increasing number of introductions of biological pesticides, including microbials and biochemicals derived from microbiological sources. These new products--including mycoherbicides, mycofungicides, and biological insecticides--are expected to become prominent control measures in the intermediate time span (10-20 years), to be supplemented in the long-term by products and transgenic plants derived from recombinant DNA technology. PMID- 2248256 TI - Setting human-health-based groundwater protection standards when toxicological data are inadequate. AB - Toxicological data are not adequate to assess fully the health effects of many of the pesticides that currently contaminate or have the potential to contaminate groundwater. The National Academy of Sciences estimated in 1984 that data to conduct a complete health hazard assessment exist for only 10% of the pesticides currently on the market. Many pesticides have not been tested for their ability to cause cancer, genetic mutation, or birth defects. There are significant gaps in the toxicological data base for the majority of pesticides for which the Environmental Protection Agency proposed health advisories in 1987. To help assure that groundwater standards are adequately protective of human health when toxicological data are not adequate, additional uncertainty factors can be incorporated into such standards. Alternatively, standards can be set at the level of detection. This should be the approach when no data exist to assess major potential health effects. For example, the detection limit could be the standard if no adequate oncogenicity studies have been conducted. In addition, generic standards may be employed when data are inadequate to set chemical specific standards. New York State has recently taken this innovative generic standard approach. PMID- 2248257 TI - Technical workshop report: Working Group II: agricultural occupational health and safety services for farmers and ranchers. AB - This work group felt that there is compelling evidence that effective occupational health services are essential to improve the serious occupational safety and health problems in agriculture. Program initiatives may be stimulated by federal and state governments, but development and implementation must involve the grassroots farm community and local resources. Other countries (Sweden, Finland, Canada) are far ahead of the United States in this area and serve as examples. Developing services should be comprehensive and should include clinical, technical, and educational efforts. Marketing programs to the public must include grassroots involvement. Surveillance and program evaluation are essential in any new program efforts. Funding such programs must be shared by federal, state, local, and private resources. Regulatory options should be a minimal part of such a program, but mandatory rollover protective devices and mandatory reporting seems to be one feasible regulatory option. PMID- 2248258 TI - Epilogue: agricultural occupational and environmental health policy strategies for the future. AB - Farmers' health and safety are critical public health problems that have historically been ignored in the United States and in many countries by health policy developers. The challenges to reduce the hazards are significant. However, by mobilizing the resources, the public will, and the structure to carry out preventive programs, progress is possible. Sweden has shown that research, education, engineering, and regulation have resulted in significant reductions of tractor rollover deaths, chainsaw injuries, and hearing loss. PMID- 2248259 TI - Pharmacists participate in AIDS Clinical Trial Group. PMID- 2248261 TI - Malfunction of syringe-pump system. PMID- 2248260 TI - Rectifying incorrect dosage schedules. PMID- 2248262 TI - Clinical pharmacy without a net. PMID- 2248263 TI - Students' attitudes toward mental illness. PMID- 2248264 TI - Effect of the prospective-pricing system on drug use in Pennsylvania long-term care facilities. AB - Health status, nondrug treatment, and drug use were compared for patients discharged from hospitals to seven long-term-care facilities (LTCFs) in Pennsylvania before and after implementation of the prospective-pricing system (PPS) for hospitalized Medicare patients. Data were collected from medical records of LTCF patients for August 1982 through July 1983 (pre-PPS) and August 1985 through July 1986 (post-PPS). Patients in the post-PPS group (n = 297) had greater numbers of illnesses and more serious illnesses on admission to the LTCFs and were more likely to be readmitted to hospitals than pre-PPS patients (n = 312). Patients in the post-PPS group required more nondrug treatments such as urinary catheters, nutritional supplements, and oxygen and received significantly more drug therapy. The cost of drugs was 50% higher in the PPS group. The post PPS patients admitted to the LTCFs apparently required more posthospital drug and non-drug therapy than the pre-PPS patients. Any system for prospective pricing in LTCFs should take into account the increases in costs for providing long-term care, including drug therapy, that have occurred since prospective pricing for hospitalized patients began. PMID- 2248265 TI - Multi-institutional drug-use evaluation of intraocular irrigating solutions. AB - A collaborative drug-use evaluation (DUE) of intraocular irrigating solutions (IOISs) at ophthalmic specialty hospitals nationwide is reported. Qualifying criteria for the use of an expensive fortified IOIS product were (1) the duration of surgery is more than 60 minutes, (2) the surgery is performed without a viscoelastic agent, (3) the patient's age is less than 50 years, (4) the patient has diabetes, and (5) the patient has evidence of compromised corneal endothelium. Surgical cases involving the use of IOISs were identified at each institution, and those cases involving fortified IOIS were reviewed for conformance with the criteria established. Of 23 institutions, 10 were able to perform the DUE. The review was concurrent at one institution and retrospective at the other nine. A case had to meet only one criterion to be considered in conformance. The cumulative mean rate of conformance with at least one criterion was 74%; the median conformance rate was 91%. The criteria that most frequently justified the use of fortified IOIS were surgical duration and nonuse of a viscoelastic material. Conformance with the DUE criteria varied with the institution, but valuable knowledge about the use of intraocular irrigating solutions was obtained by all. PMID- 2248266 TI - Ethical dimensions of patient drug charges. PMID- 2248267 TI - Health-insurance products and plan options. AB - Trends in health insurance are discussed, with emphasis on insurers' efforts to offer an array of cost-effective plans tailored to the needs of employers and subscribers. Health-insurance companies, responding to employers' demands to curtail the rising costs of premiums, now offer a variety of insurance products. While indemnity plans, health maintenance organizations (HMOs), and preferred provider organizations (PPOs) remain as the three basic types of plans, insurers are combining these elements in different ways, creating dual- and triple-option plans that consist of indemnity insurance and an HMO, a PPO and an HMO, or other variations. Insurers offering multiple options may effect internal cost savings through shared personnel and administrative expenses. Four factors influence the development and marketing of insurance products: cost and volume of healthcare services, adverse selection, competition, and the profit incentive. Many of the insurance products have been developed in response to requests for maximum freedom of choice of provider; as an example, the fastest-growing HMO product in 1989 was the point-of-service HMO, which allows the subscriber to seek care from a provider who is not part of the HMO network. PPOs and exclusive-provider organizations (EPOs) are growing; these are often organized by hospitals or physician networks. Among the new trends in product-line development are "riders" for specialty services such as vision care and prescription drugs. As competition intensifies, marketing efforts are focusing on previously overlooked groups such as the small employer and certain ethnic communities. Cost and freedom of choice will remain important criteria in the selection of insurance products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248268 TI - Member satisfaction in a staff-model health maintenance organization. AB - The results of a June 1988 member-satisfaction survey undertaken by a staff-model health maintenance organization (HMO) are presented, and implications for HMO management are discussed. Focus groups identified key reasons for consumer satisfaction; results were incorporated into a telephone survey that was administered to 600 households randomly selected from among enrollees and to an equal number of nonenrollees in the same region. Questions covered five areas: (1) importance-of-health-plan issues, (2) predictors of health-plan satisfaction, (3) importance-of-provider issues, (4) predictors of satisfaction with providers, and (5) demographics and use of services. Comprehensiveness of coverage was the most important factor in selection of a health plan; cost ranked second. Factors related to health-plan satisfaction included quality and quantity of plan physicians, access to specialists, and scope of benefits. Analysis of the dependent variable, perceived quality of physician care, revealed that physician technical skills, physician availability after hours, and equipment and facilities were among the highest-ranking factors. Enrollees were significantly more satisfied with their health plan overall than were members of preferred provider organizations or indemnity health plans. Management concluded that member satisfaction was related to the number of physicians available and the ease of access to a preferred physician. Physician quality appeared to be the prime determinant of member satisfaction. Competition will spur health plans to place more interest on identifying and responding to member preferences. PMID- 2248269 TI - Managed care is utilization review. AB - The role of utilization review (UR) as a form of managed care is described. As technology has advanced, the use of diagnostic and therapeutic services has increased and care delivery has shifted to outpatient settings, but the increase in healthcare costs has not slowed. The shift to delivery of medical care outside the hospital setting has increased the need for effective UR in both inpatient and outpatient settings. UR is performed not only by private UR organizations and through external review programs of insurance carriers but also through care providers' internal programs. UR has been driven by increased medical costs and by redesign of insurance benefit plans to include financial incentives and penalties and copayments. UR has attempted to control the use of hospital services through preadmission certification and concurrent review, requirements for second surgical opinions, and medical case management, which is the identification before or during hospitalization of patients who could safely receive treatment outside the hospital. In-patient mental health and substance abuse programs have been the subject of intensive review because of high expenditures for such services. Practice indicators are being developed that will be used for prospective determination of treatment plans. As UR techniques improve, management of care in all organized health-care settings will intensify. PMID- 2248270 TI - Case studies of hospital pharmacist involvement in managed care. Memorial Medical Center. PMID- 2248271 TI - Case studies of hospital pharmacist involvement in managed care. Stanford University Hospital. PMID- 2248272 TI - Pharmacy involvement in interdisciplinary quality assurance activities. PMID- 2248273 TI - Cost of training doctor of pharmacy students in a clinical practice setting. PMID- 2248274 TI - Cimetidine suppresses chemically induced experimental hepatic porphyria. AB - The ability of cimetidine to reduce the activity of hepatic aminolevulinic acid synthase (ALA-S) was examined in allylisopropyl acetamide (AIA) treated porphyric adult rats. A dose of 20 mg cimetidine/100 gm body weight resulted in a 50% decrease in the AIA-induced hepatic ALA-S activity compared to rats treated with AIA alone. Heme oxygenase activity was decreased 25% compared to rats treated with AIA alone. The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans. PMID- 2248275 TI - Bone mineral density in spontaneous hypertension: differential effects of dietary calcium and sodium. AB - Dietary calcium and sodium have been postulated to modify both bone mineral status and blood pressure regulation in humans and animals. The spontaneously hypertensive rat (SHR) manifests several defects in calcium metabolism that may contribute to its hypertension. Blood pressure and bone mineral status were measured in SHR and normotensive Wistar-Kyoto rats (WKY) as a marker of whole animal calcium metabolism. In addition, the effect of alterations in dietary calcium and sodium on bone status were examined. At 6 weeks of age, seven male SHR and seven male WKY were placed on a control diet. At the same age, 28 SHR and 28 WKY were randomized to four diets containing either 2.0% or 0.1% calcium and 1.0% or 0.25% sodium. Four markers of bone mineral status were analyzed: bone density measured by direct photon absorptiometry, and total bone calcium, phosphorus, and magnesium content measured by atomic absorption spectrophotometry. The SHR exhibited significantly lower levels (p less than 0.001) of bone density and bone magnesium content than the WKY, whereas bone phosphorus and calcium did not differ between the two strains. The 2.0% calcium diets resulted in increased bone density and bone calcium content, and lower bone magnesium in both strains. The 1.0% sodium diets were associated with decreased bone density in the SHR, but not in the WKY. These findings identify another indicator of disturbed calcium metabolism in the SHR that may be related to impaired renal calcium handling. They are consistent with previously reported reductions in renal calcium reabsorption and decreased intestinal calcium transport in older SHR. PMID- 2248276 TI - Corporectomy for intractable sickle-associated priapism. AB - Priapism is a complication of sickle cell disease, and for those with severe prolonged attacks, it is serious, often resulting in permanent sexual impairment. Treatment is frustrating, and psychological consequences may be profound. A 20 year-old sickle cell patient with intractable priapism associated with intense pain and penile gigantism underwent multiple but unsuccessful medical and surgical treatment regimens. Finally, corpora cavernosa corporectomy was performed. The pathologic findings of extensive vascular thrombosis and stromal fibrosis underscore the irreversibility of this process and explain the inevitable impotence. Pain and sexual impairment were associated with serious psychological difficulties and suicide attempts. Counseling and close follow-up have improved his outlook considerably. He has been pain-free for 1 year, and future management includes consideration of placement of a penile prosthesis. PMID- 2248277 TI - Possible triggering of paroxysmal atrial fibrillation in normal hearts by psychological stressors: a report of two cases. AB - Paroxysmal atrial fibrillation was triggered by psychological stress in two patients, both of whom had normal echocardiograms and coronary angiography. Neither patient was alcoholic or had ingested ethanol in relation to the onset of atrial fibrillation and both were free of metabolic derangements. Possible mechanisms involved in the triggering of atrial fibrillation are discussed. PMID- 2248278 TI - Southern blood club symposium: an update on selected aspects of hemochromatosis. AB - Genetic epidemiology studies have indicated that hereditary hemochromatosis (HH) occurs in caucasians with a frequency of 3 to 13 per thousand. Clinical recognition however occurs far less frequently. The disparity is best resolved by defining HH as homozygosity for the HLA-linked hemochromatosis allele, regardless of the total body iron burden. Variability of clinical expression is explained in part by physiologic iron loss in women but variability in males may be due to environmental factors, gene-gene interactions or polymorphisms in mutated hemochromatosis alleles. Although clinical variability is great, the laboratory phenotype of HH is fairly constant and is marked by elevation of the transferrin saturation. The elevated transferrin saturation occurs early in life, before organ iron loading occurs and can be used as a screening tool to detect HH before organ damage occurs. Cloning and characterizing the HH gene, which is located within 1 centimorgan of the HLA-A locus should resolve some of the issues concerning clinical variability. PMID- 2248279 TI - Hypersensitivity pneumonitis. AB - The lung is constantly exposed to a wide variety of environmental insults. In its defense against these environmental challenges, however, the lung responds through a limited number of pathophysiologic mechanisms. This is well illustrated by a group of diseases which are collectively referred to as hypersensitivity pneumonitis. This syndrome includes a very large number of different diseases. However, in the United States, only farmer's lung, bird-breeder's lung, and ventilation hypersensitivity pneumonitis occur with any significant frequency. Each of these is characterized by flu-like symptoms, in conjunction with a pneumonitis consisting of lymphocytic granulomatous infiltration of the alveoli and terminal bronchioles. This disease is caused by the inhalation of antigenic material which usually originates from the dusts of organic material. A host of different dusts and antigens have been described in conjunction with hypersensitivity pneumonitis but each leads to the same characteristic clinical syndrome. Thus, each of the diseases shares similar clinical features but differs primarily with respect to the nature of the exposure and causative antigens. The clinical features, pathogenesis, course, prognosis, and treatment of these related diseases are reviewed. PMID- 2248280 TI - Octreotide: a long-acting somatostatin analog. AB - One of the exciting recent developments in endocrinology research has been the introduction of the somatostatin analog, octreotide into clinical practice. Octreotide provides a new therapeutic tool for diseases in which somatostatin or somatostatin-like products are secreted abnormally. Unfortunately, early experience was obtained largely with uncontrolled, compassionate drug use. When clinical information regarding octreotide is critically reviewed, evaluation is hampered by the lack of long-term studies with adequate numbers of patients and controls. Nevertheless, the information available does indicate that octreotide is promising in the acute treatment of some of the manifestations of the carcinoid syndrome, including carcinoid crisis. Similarly, octreotide ameliorates symptoms of other gut neuroendocrine tumors, particularly vasoactive intestinal peptide (VIP)-secreting tumors. Octreotide also has potential in the management of growth-hormone-secreting tumors. Long-term treatment with octreotide for these diseases requires more information regarding alterations in disease progression and development of adverse effects including variable effects on blood sugar regulation and steatorrhoea. Octreotide also has been used in nonmalignant gastrointestinal disorders, but larger studies are necessary before recommendations regarding these applications can be made. The cost of octreotide, as may be expected, is high but is justified for patients with the specific indications outlined in this review. These indications may change as understanding of the drug increases. Octreotide offers promise, particularly as acute treatment for the troublesome symptoms of several neuroendocrine disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248281 TI - Marfan syndrome associated with bicuspid aortic valve, premature aging, and primary hypogonadism. AB - We report and discuss a patient with characteristics of Marfan syndrome associated with a bicuspid aortic valve, premature aging, and primary hypogonadism. PMID- 2248282 TI - Rearrangement of chromosome 15 in the region q11.2----q12 in an individual with obesity syndrome and her normal mother. AB - Rearrangement of the proximal long arm of chromosome 15 have been found in most patients with the Prader-Willi syndrome (PWS) and in some with Angelman syndrome. We present an individual with syndromic obesity and her normal mother, who both have an abnormal chromosome 15. The proposita is a 26-year-old women with marked obesity, acanthosis, nigricans, short fingers, and severe cone degeneration of the retina. She has high plasma insulin levels, hypothyroidism, and an empty sella on CT scan. High-resolution chromosome banding demonstrated an increase in band 15q12. Further analysis showed the same abnormal 15 in her normal mother but not in her normal sister. This case and recent reports in the literature indicate that duplication of chromosome 15q in the PWS region may be associated with a syndrome of obesity, acanthosis nigricans, empty sella, and rodcore dystrophy as well as with a normal phenotype. Whether normal individuals with such a duplication carry increased risk of having offspring with an obesity syndrome is yet to be determined. PMID- 2248283 TI - Clinical anophthalmia, dextrocardia, and skeletal anomalies in an infant born to consanguineous parents. PMID- 2248284 TI - Microphthalmia and chorioretinal lesions in a girl with an Xp22.2-pter deletion and partial 3p trisomy: clinical observations relevant to Aicardi syndrome gene localization. AB - We present a 4-year-old girl with a maternally derived, unbalanced X;3 translocation resulting in partial Xp monosomy and partial 3p trisomy. She had chorioretinal defects, developmental delay, infantile seizures, and microphthalmia. These findings initially suggested a diagnosis of Aicardi syndrome. However, she had a normal-appearing corpus callosum on CT and magnetic resonance imaging scans of the brain and her retinal findings were not typical for Aicardi syndrome. This represents the 6th reported example of microphthalmia associated with an Xp22 chromosome abnormality. Four of these individuals also had features suggestive of focal dermal hypoplasia (FDH), which was not evident in our patient. The available evidence supports the hypothesis that gene disruption at Xp22 may lead to findings similar to those seen in Aicardi syndrome and FDH, both of which are believed to be X-linked dominant male lethal conditions. PMID- 2248285 TI - Patterns of mood states in pregnant women undergoing chorionic villus sampling or amniocentesis. AB - The purpose of this study was to compare patterns of self-reported mood states of women having chorionic villus sampling (CVS) (n = 151) to those of women electing amniocentesis (n = 30) with the indication of advanced maternal age. Mood states were defined as scores on the 6 subscales of the Profile of Mood States (POMS). Women at 4 U.S. prenatal diagnostic facilities completed the POMS at 4 assessment periods. These were a) at their initial genetic counseling session, b) 2 weeks post CVS results (or an equivalent time), c) 2 weeks post amniocentesis results (or an equivalent time), and d) at 30 weeks gestation. Repeated measures analysis of variance revealed that anxiety, fatigue, and confusion decreased, and vigor increased in both groups as the pregnancy progressed. Depression decreased in both groups and then increased at assessment 4 in women in the amniocentesis group but not in those electing CVS. Results should be interpreted in conjunction with obstetrically and genetically-oriented findings regarding safety and accuracy to help women decide between the 2 procedures. PMID- 2248286 TI - Chondrodysplasia punctata, tibia-metacarpal (MT) type. AB - We describe 7 patients with a new form of chondrodysplasia punctata. Its principal clinical manifestations are flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn infant are discrete calcific stippling, coronal clefts of vertebral bodies, short tibiae, and shortness of the 2nd and 3rd metacarpal bones. Radiologic findings in the older child include shortness of tibiae and the 3rd and 4th metacarpals. PMID- 2248287 TI - New type of X-linked progressive muscular dystrophy involving shoulder girdle and back. AB - A new type of X-linked muscular dystrophy is described in a family in which 7 men had boyhood onset of progressive dystrophy involving muscles of the shoulder and back but not the calves or face. The scapula-back muscles are affected, but the calf muscles are normal. All patients are still able to walk. The oldest patient is now 37 years old. The muscular dystrophy has been specified by electromyography, pathologic tissue microscopic examination, electron microscopic study, and elevated CK. This type of muscular dystrophy has not been reported previously. PMID- 2248288 TI - GAPO syndrome (McKusick 23074)--a connective tissue disorder: report on two affected sibs and on the pathologic findings in the older. AB - GAPO syndrome was described in 12 patients from 7 families. Constant manifestations include dwarfism, alopecia, pseudoanodontia, and a peculiar, "geriatric" facial appearance. We describe the autopsy findings and all available clinical data on one deceased patient and his living affected sister, previously reported as short abstracts (Epps et al.: Cienc Cult 29(Suppl):740, 1977; Wajntal et al.: Cienc Cult 34(Suppl):705, 1982). Both had the characteristic anomalies of this syndrome but optic atrophy was absent; instead, they had glaucoma and keratoconus; hypogonadism was present in both patients. Biopsy and autopsy findings show that the GAPO syndrome is a dyshistogenetic sequence due to accumulation of extracellular material and thus should be called GAPO dysplasia. We suggest that the basic defect in this autosomal recessive disorder is possibly related to a lack of breakdown of the extracellular components, perhaps due to an enzyme deficiency involved in the metabolism of extracellular matrix. PMID- 2248289 TI - Ullrich-Turner syndrome with agenesis of the corpus callosum. AB - We report on a 19-year-old woman with 45,X Ullrich-Turner syndrome who was severely mentally retarded and had hypotonia. Computer tomography (CT) scan showed agenesis of the corpus callosum. There have been few reports of gross developmental central nervous system (CNS) abnormalities in Ullrich-Turner syndrome. Only one case of Ullrich-Turner syndrome with agenesis of the corpus callosum has been reported. The high prenatal lethality of Ullrich-Turner syndrome may mask a CNS abnormality. PMID- 2248290 TI - On the measurement and interpretation of birth defect associations in epidemiologic studies. AB - The extent of clustering of 2 or more defects in the same infant can be expressed as the ratio of the observed number of infants with the defects (O) over the expected number of such infants (E). The expected is usually derived from the product of population rates of individual defects. Because large O/E ratios are obtained for many defect combinations, it has been suggested that clustering of defects is generalized and nonspecific. To control for the tendency of nonspecific clustering of defects, an alternative method is to perform the same calculations among multimalformed infants only. A main limitation of this method is that it adjusts for the clustering tendency of all defects rather than the ones of interest, often resulting in spuriously low O/E ratios. We present a new method to adjust for the tendency for nonspecific clustering between defects that overcomes this limitation. With this method, adjusted O/E ratios are inversely related to the proportion of infants who are multimalformed and have one or more of the defects being examined. Using data from the Metropolitan Atlanta Congenital Defects Program, we apply this method to the previously described associations among VACTERL defects and midline or "schisis" defects. We show that adjusted O/E ratios obtained are greater than those obtained by using multimalformed infants. For midline defects, many of the adjusted ratios were close to one, indicating nonspecific clustering of these defects. Finally, using the example of isotretinoin embryopathy, we show that O/E ratios depend highly on the frequency of exposure in the population, and thus, they should be interpreted with caution. PMID- 2248291 TI - Arthrogryposis, cholestatic pigmentary liver disease and renal dysfunction: report of a second family. AB - We report on a boy, born to consanguineous parents, who had arthrogryposis, cholestatic liver disease, and renal dysfunction. The child died at age 2 months, and autopsy showed pigmentary storage disease in liver cells, nephrocalcinosis, and rarefaction of motor neuron cells in the anterior horns of spinal cord. This association, reported in 1979 by Nezelof et al., is a distinctive syndrome. The possibility of an autosomal recessive or an X-linked inheritance is discussed. PMID- 2248292 TI - New findings in a patient with Dubowitz syndrome: velopharyngeal insufficiency and hypoparathyroidism. AB - We report on a boy with Dubowitz syndrome and hypoparathyroidism from which he recovered, only to redevelop it at 6 years. He also had a submucous cleft palate and cineradiographic studies showed velopharyngeal insufficiency. Although a submucous cleft palate is a well-known manifestation of Dubowitz syndrome, velopharyngeal insufficiency has not been previously described. PMID- 2248293 TI - Chromosome lesions which could be interpreted as "fragile sites" on the distal end of Xq. AB - Chromosome lesions which could be interpreted as "fragile sites" on the distal end of the long arm of the X chromosome were identified during a cytogenetic study of 160 mentally retarded adult males with no apparent cause of their mental retardation and one normal adult female with a family history of fra (X) syndrome. Peripheral blood samples were cultured in either M199 or RPMI 1640 medium with FUdR or BrdU. Metaphases were examined for chromosome lesions or fragile sites on the distal end of Xq and 3 distinct sites were observed: Xq26, Xq27.2, and Xq27.3. Other chromosome lesions at Xq28 were observed and interpreted as nonspecific telomeric structural changes. Chromosome lesions were observed in cells from 14 of the 161 individuals. These included: 5 patients with an Xq26 site, 2 with the recently reported Xq27.2 site, 4 with the Xq27.3 site (characteristic of the fra (X) syndrome), 2 with nonspecific telomeric structural changes, and one individual with 2 lesions (a nonspecific telomeric structural change and an Xq26 site). Additional research is necessary to determine the frequency and clinical significance, if any, of lesions occurring in this region of the X chromosome and to distinguish among heritable fragile sites, constitutive fragile sites, and nonspecific telomeric structural changes. PMID- 2248294 TI - Clinical diagnosis of partial duplication 7q. AB - We report on two sibs with partial dup (7q), a retarded 9-month-old boy and an aborted fetus of 17 weeks' gestational age. Besides minor anomalies, the boy had frontal bossing, macrocephaly with hydrocephaly, a high forehead, and a large fontanelle. GTG banded chromosomes showed a 14p+ abnormality. Because his mother carries a balanced, de novo translocation with a breakpoint in band 7q33, the boy has a duplication of the distal portion of band 7q33 and the segment 7q34--- qter. Our findings suggest that the phenotype in terminal duplications of 7q may, in some patients, be recognized clinically. PMID- 2248295 TI - Ulnar agenesis and endocardial fibroelastosis. AB - We report on an infant with bilateral ulnar agenesis, radial hypoplasia, oligodactyly, hydrops fetalis, and endocardial fibroelastosis (EFE). The presence of the 2 major malformations and parental consanguinity suggests the possibility of a new autosomal recessive MCA syndrome. PMID- 2248296 TI - Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies. AB - In 3,000 chorionic villi studies (CVS) 33 cases of mosaicism and 7 false-positive cell lines in all cells were seen. The mosaic cell lines were caused by aneuploidy of autosomes (13x), sex chromosomes (9x), and structural anomalies (11x). Mosaics of fetal origin were only 4 cases of trisomy 21 and one 47,XXY mosaic. In 7 cases abnormal karyotype of non-fetal origin was seen in all cells in direct studies, including trisomy 16 (3x) and trisomy 18 (2x). The combined use of direct CVS and cell cultures always uncovered the non-fetal origin of chromosome abnormalities and the study of cultured cells in all cases could have prevented 5 terminations. Complete follow-up studies demonstrated no false negative results. Therefore, CVS can be nearly 100% accurate when both direct studies and cultures are examined in cases of mosaicism and other cell lines of possible non-fetal origin, such as trisomy 16, trisomy 18, translocation (21;21), and 45,X cells. PMID- 2248297 TI - Clinical manifestation of prenatal exposure to valproic acid using case reports and epidemiologic information. AB - The present study includes 28 patients prenatally exposed to valproic acid (VPA) monitored by the Spanish Collaborative Study of Congenital Malformations (ECEMC), from April 1976 to December 1988. Among the 28 cases, 15 (53.6%) were exposed only to VPA and 13 (46.4%) to VPA plus other anticonvulsant drugs. The clinical manifestations observed in those prenatally exposed only to VPA, are compared with the abnormalities observed in those with prenatal exposure to VPA plus other anticonvulsant drugs. To better define the spectrum of clinical manifestation of the prenatal exposure to VPA we used, besides our clinical observations and those from the literature, all available epidemiological data. We consider that a "valproate embryofetopathy (VPEF)" could exist, because different anomalies have been observed in children prenatally exposed to VPA in monotherapy. A facial phenotype of VPA exposure has been reported, and epidemiologic studies have shown an increased risk for congenital defects. However, from a review of published cases as well as those in the present study, it appears that the spectrum of VAE in monotherapy may not include oral clefts. PMID- 2248298 TI - Mental retardation, short stature, almond-shaped eyes, small downturned mouth and coned epiphyses: a new case of Hunter-Fraser syndrome. AB - A 21-year-old male with mental retardation, short stature, almond-shaped eyes, small downturned mouth, and coned epiphyses is presented. The clinical presentation, as well as the metacarpal phalangeal pattern profile, was similar to the affected members of a family reported by Hunter et al.: (Hunter et al.: J Med Genet 14:430-437, 1977). In addition, many features of our patient resembled Ruvalcaba syndrome. However, skeletal abnormalities were different. A reciprocal translocation was also observed in 3 members of our patient's family. PMID- 2248299 TI - Agnathia, holoprosencephaly, and situs inversus: a third report. AB - We report on a male infant with cyclopia, agnathia, and situs inversus. In addition, anal atresia and horseshoe-kidneys were present. To our knowledge, this is the third published case of the "agnathia-holoprosencephaly-further midline defects association." PMID- 2248300 TI - The translocation 11q;22q: a novel unbalanced karyotype. PMID- 2248301 TI - Duchenne-like muscular dystrophy in the Arabs. PMID- 2248302 TI - X-linked microphthalmia syndrome. PMID- 2248303 TI - Chromosome plotbooks and diskettes available from the Human Gene Mapping Library. PMID- 2248304 TI - Genee-Wiedemann syndrome in a family. PMID- 2248305 TI - Parental origin of del(15)(q11-q13) in Angelman and Prader-Willi syndromes. PMID- 2248306 TI - Clinically recognizable chromosomal abnormalities in newborn infants. PMID- 2248307 TI - Pseudotrisomy 13 syndrome. PMID- 2248308 TI - Precocious mortality in Christ-Siemens-Touraine syndrome. PMID- 2248309 TI - Rewarding research. PMID- 2248310 TI - Doing what we want. PMID- 2248311 TI - AIDS: the way it is. PMID- 2248312 TI - Questions nurses ask about pacemakers. How they work--and what to do when they don't. PMID- 2248313 TI - What really interferes with pacemakers? PMID- 2248315 TI - Anaphylactic shock. PMID- 2248314 TI - Nurse-midwifery: the window is wide open. PMID- 2248316 TI - Southeast job focus. Southern exposure: hospitality and health care. PMID- 2248317 TI - Florida job focus. Florida: comfort and challenge. PMID- 2248318 TI - Breast feeding. PMID- 2248320 TI - Hospital upheld on AIDS test. PMID- 2248319 TI - The last four weeks of life. PMID- 2248321 TI - Nurse infected with HIV virus urges others to take care. PMID- 2248322 TI - Identification of Toxoplasma gondii in paraffin-embedded sections by the polymerase chain reaction. AB - We used the polymerase chain reaction to amplify DNA fragments specific to Toxoplasma gondii. The sensitivity of the technique allowed for the detection of as few as ten cultured T. gondii tachyzoites. We applied the same amplification technique to deparaffinized ocular sections from two cases of ocular toxoplasmosis. Although toxoplasmic cysts could only be seen in one eye by optical microscopy, polymerase chain reaction allowed the identification of the parasite in both cases. Our study indicates the feasibility of a sensitive DNA based assay to complement pathologic studies of an ocular parasitic disease. PMID- 2248323 TI - Parental age in sporadic hereditary retinoblastoma. AB - Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma. PMID- 2248324 TI - Epiretinal membrane contracture associated with macular prolapse. AB - We treated two patients with annular epiretinal membranes that produced unusual macular morphologic characteristics. Contracture of the membranes caused herniation of macular tissue through a hole in the center of the membrane. The membranes were removed surgically, and ultrastructural analysis disclosed cells with properties resembling myofibroblasts and apparent new vitreous collagen. Contracture of the cellular components probably produced tangential traction on the retina, which caused prolapse of the retinal tissue through a central defect in the membrane. PMID- 2248325 TI - Experimental endoretinal biopsy. AB - We performed transvitreal endoretinal biopsy in rabbit eyes to develop a reliable and safe technique to obtain retinal specimens from attached retina. Pars plana vitrectomy without lensectomy was followed by injection of Ringer's solution into the subretinal space to produce a focal retinal detachment. The apex of the focal detachment was excised by intraocular scissors and removed from the eye by pneumohydraulic expulsion. A fluid-air exchange reattached the retina. The biopsy sites were evaluated clinically and by light and electron microscopy at regular intervals up to 20 weeks postoperatively. The initial five procedures were performed without heparin in the infusion fluid, and they were complicated by severe fibrin reaction and early retinal detachment. Of the remaining 17 eyes, 15 were without intraoperative complication and maintained attached retinas. The biopsy site developed an early ring of hyperpigmentation along the border, and the biopsy bed became increasingly hyperpigmented because of cytoplasmic hyperplasia and hypertrophy of the pigment epithelium. Epiretinal membranes and subretinal neovascularization were observed histologically. Retinal biopsy specimens were reproducible and suitable for diagnostic studies. PMID- 2248326 TI - Acanthamoeba keratitis associated with disposable contact lenses. AB - Two patients developed Acanthamoeba keratitis associated with the use of disposable extended-wear hydrogel contact lenses. Both patients removed, irrigated, and reinserted the contact lenses without disinfecting them. One patient wore the lenses on a daily basis, rinsed the lenses in tap water, stored them overnight, and discarded them weekly. Both infections were treated successfully. In a third patient, Acanthamoeba species was cultured from two pairs of disposable lenses that had been stored in cases rinsed with well water. Potential benefits from disposable contact lens wear are negated when patients do not comply with a continuous wearing schedule. PMID- 2248327 TI - Ocular injury induced by methyl ethyl ketone peroxide. AB - Methyl ethyl ketone peroxide is a commonly used catalyst in various industries. We studied 19 eyes with a single exposure to methyl ethyl ketone peroxide that developed clinical patterns of mild injury, moderate injury, severe injury, or delayed keratitis. Delayed methyl ethyl ketone peroxide keratitis may cause exacerbations and remissions of corneal and limbal disease lasting more than 20 years with palpebral and bulbar hyperemia equal to the initial chemical exposure. With repeat exacerbation, further pannus may occur, which can be associated with a poorer outcome. Based on the capability of methyl ethyl ketone peroxide to change DNA to a new weak antigen, we suggest possible methods of therapy to prevent or limit delayed methyl ethyl ketone peroxide keratitis. This proposed type of injury has important implications in studying various limbal and corneal diseases. A major factor in the severity of ocular injury was the length of time from exposure to methyl ethyl ketone peroxide to obtaining a topical ocular local anesthetic to perform adequate lavage. PMID- 2248328 TI - Topical use of cyclosporine in the treatment of vernal keratoconjunctivitis. AB - We treated 11 patients with vernal keratoconjunctivitis for four to nine months with topical cyclosporine as a 2% dilution in castor oil. No significant side effects occurred, except for mild and transient burning upon administration. Within the first 15 days, both symptoms and signs of the condition improved significantly, and these results were maintained throughout the entire treatment. Relapses of the disease occurred two to four months after the end of the therapy. A double-masked clinical trial of nine patients (2% cyclosporine in castor oil vs castor oil alone) confirmed the results. Treated eyes improved significantly for both signs and symptoms as compared to control eyes. Topical cyclosporine may, therefore, be considered an effective substitute for corticosteroids, with an excellent anti-inflammatory activity in patients with both corticosteroid dependent and corticosteroid-resistant vernal keratoconjunctivitis. PMID- 2248329 TI - The corneoscleral limbus in human corneal epithelial wound healing. AB - We studied re-epithelialization of the ocular surface in 17 human eyes (14 patients) with large corneal and conjunctival abrasions. We focused on the healing of the limbal region. During re-epithelialization, cell movement was found to occur circumferentially along the corneoscleral limbus and centripetally from the corneoscleral limbus. In no patient did the central corneal defect close before the corneoscleral limbus had first re-epithelialized completely. Normal limbal healing was observed to occur by circumferentially migrating tongue-shaped corneal limbal epithelium. These tongue-shaped projections developed from either side of the remaining intact epithelium and advanced along the corneoscleral limbus until they met. A centripetal movement of cells from the corneoscleral limbus then completed the healing process. In three patients, however, the advancing conjunctival epithelium extended across the corneoscleral limbus before the tongue-shaped projections of corneal limbal epithelium had met. The surface of the cornea covered by conjunctival epithelium was thin and irregular, and later showed peripheral scarring, vascularization, and recurrent erosions. PMID- 2248330 TI - Anisocoria in the pigmentary dispersion syndrome. AB - We studied four patients with anisocoria and the pigmentary dispersion syndrome. In all patients, the larger pupil was on the side of the greater iris transillumination. The amount of anisocoria was between 0.5 and 1.5 mm and was the same in both the light and dark. There was no blepharoptosis, and all pupils dilated normally with cocaine. All of the patients were young men with myopia, and one patient had increased intraocular pressure. PMID- 2248331 TI - Glucose 6-phosphate dehydrogenase deficiency and cataract of patients in northern Sardinia. AB - We determined the activity level of glucose 6-phosphate dehydrogenase in 467 patients with cataract from northern Sardinia. Of 226 men, 18 (8%) had glucose 6 phosphate dehydrogenase deficiency. Of 241 women, 30 (12%) were heterozygous and two (1%) were homozygous for glucose 6-phosphate dehydrogenase deficiency. These prevalences were not significantly different from those expected in the general population. We concluded that patients with glucose 6-phosphate dehydrogenase deficiency do not have a higher risk of developing cataract. PMID- 2248332 TI - Treatment of traumatic optic neuropathy with corticosteroids. AB - We treated 21 patients (22 eyes) with traumatic optic neuropathy by using intravenous megadose methylprednisolone (13 patients) or high-dose dexamethasone (eight patients). Of 13 patients treated with megadose methylprednisolone, 12 had improved visual function, as did seven of nine eyes treated with intravenous dexamethasone. This difference was not significant (P = .3). Initial total blindness, mechanism of injury, or time from injury to treatment did not correlate with visual improvement. PMID- 2248333 TI - Laser placement in noncontact Nd:YAG cyclophotocoagulation. AB - We treated 40 eyes of 40 patients by using noncontact transscleral Nd:YAG cyclophotocoagulation to determine whether treatment 1.5 or 3.0 mm posterior to the corneoscleral lumbus was preferable. Patients were randomly assigned to one of the treatment groups, and all other variables, including power, number, and distribution of laser applications, were kept constant. Six months postoperatively, those treated 1.5 mm posterior to the corneoscleral limbus had a lower intraocular pressure (P = .0047) than those treated 3.0 mm from the corneoscleral limbus. The 1.5-mm group also required fewer retreatment (P = .017) and had a slightly lower occurrence of visual acuity loss after this procedure. We believe it may be advantageous to locate the laser application approximately 1.5 mm posterior to the corneoscleral limbus, rather than further posteriorly, when performing noncontact transscleral Nd:YAG cyclophotocoagulation. PMID- 2248334 TI - Ocular movements in essential blepharospasm. AB - In essential blepharospasm histopathologic and electrophysiologic evidence supports the existence of lesions in proximity to brainstem nuclei controlling ocular movements. We studied horizontal ocular movements in eight patients who had been treated previously with surgery or botulinum toxin injection to control essential blepharospasm (mean age, 58 years) and compared these with seven control subjects who did not have blepharospasm (mean age, 68 years). We examined fixation stability, saccades, the vestibulo-ocular reflex, visual enhancement and suppression of the vestibulo-ocular reflex, optokinetic nystagmus, and pursuit by using digitally sampled, direct current electro-oculography. Patients with blepharospasm exhibited no ocular movement abnormalities. Since quantitative aspects of ocular movements are sensitive to nonspecific brainstem lesions, the absence of abnormal ocular movements suggests that the lesion in blepharospasm is specifically limited to neurons regulating the facial muscles. PMID- 2248335 TI - Antibiotic therapy for Bacillus species infections. AB - We reviewed 36 cases of culture-proven Bacillus species ocular infections occurring between September 1974 and December 1989. Kirby-Bauer disk sensitivities were available in 34 of the 36 cases (95%). All Bacillus species isolates were sensitive to the aminoglycoside antibiotics (N = 34) and to vancomycin hydrochloride (N = 32); resistance to clindamycin was found in four of 18 (22%) of tested isolates. Although B. cereus was uniformly sensitive to these antibiotics, resistance to clindamycin occurred in four cases in the non-B. cereus group. The microbroth dilution technique confirmed the Kirby-Bauer data. The aminoglycosides were uniformly effective, but the cephalosporins (first, second, and third generation drugs) were consistently ineffective against B. cereus and varied from sensitive to moderately sensitive for the non-B. cereus isolates. Our microbiologic laboratory findings suggest that vancomycin hydrochloride in combination with an aminoglycoside ensures more consistent antibiotic coverage of Bacillus species ocular infections. PMID- 2248336 TI - Professionalism, specialization, and competition. PMID- 2248337 TI - Incontinentia pigmenti. PMID- 2248338 TI - Treatment of proliferative retinopathy associated with incontinentia pigmenti. PMID- 2248339 TI - Recurrent bilateral panuveitis and rhegmatogenous retinal detachment in a patient with familial Mediterranean fever. PMID- 2248340 TI - Neuroretinitis associated with cat scratch disease. PMID- 2248341 TI - Superior ophthalmic vein enlargement and proptosis caused by middle cranial fossa lipoma. PMID- 2248342 TI - Orbital findings in acquired immunodeficiency syndrome. PMID- 2248343 TI - Adenocarcinoma of the stomach confirmed by orbital biopsy in a patient seropositive for human immunodeficiency virus. PMID- 2248344 TI - Computed tomographic appearance of extraocular muscle calcification in a patient with seropositive trichinosis. PMID- 2248345 TI - Transmission of light through cataracts. PMID- 2248346 TI - Why cataracts do not produce afferent pupillary defects. PMID- 2248347 TI - Spontaneous lens subluxation in uveitis. PMID- 2248348 TI - Hydroxyamphetamine mydriasis in normal subjects and hydroxyamphetamine mydriasis in Horner's syndrome. PMID- 2248349 TI - Formulating a role for occupational therapy in child psychiatry: a clinical application. AB - Occupational therapy is in need of role clarification within the specialty of child psychiatry. The literature reveals that occupational therapy is often undelineated or unrecognized by child psychiatry, has limited efficacy research, and may be at risk for losing its practice with children hospitalized for psychiatric disturbances. This paper outlines steps for the formulation of a specialized role for occupational therapy within this specialty. The Model of Human Occupation (Kielhofner, 1985) is suggested as a basis for conceptualizing this role. A clinical study focused on the evaluation of adaptive functioning with use of the Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984, 1985) is presented as an example of a way in which occupational therapy can provide assessment data valuable to the interdisciplinary clinical team. The role of occupational therapy in both short-term and long-term hospitalization of children with psychiatric disturbances is described. PMID- 2248350 TI - The zone of proximal development in in-hand manipulation skills of nondysfunctional 3- and 4-year-old children. AB - The purpose of this study was to assess the influence of verbal and visual cues on 28 nondysfunctional 3- and 4-year-old children's performance of in-hand manipulation skills. During the uncued version of the test (pretest), the children were presented with play activities known to elicit in-hand manipulation skills in young children but were given no cues for specific manipulative skill use. Within 1 week of the pretest, after the children were randomly assigned to groups, a posttest was given in which the children were provided with verbal or visual cues. The results indicate that both visual and verbal cues were effective in increasing the groups' test scores, but no significant differences were found based on the type of cue provided. Approximately 30% of the children in the study showed marked improvement on the posttest scores, whereas the others showed little change. The children who had lower pretest scores showed greater score increases on the posttest than did the children who scored somewhat higher initially. The use of an uncued test followed by a cued test may be an effective method for the identification of those children who are most likely to show improvement in these manipulation skills with intervention. This study's findings lend tentative support to Vygotsky's (1978) zone of proximal development theory and extends the application of his work into the domain of fine motor skills. PMID- 2248351 TI - Descriptive analysis of the developmental progression of grip position for pencil and crayon control in nondysfunctional children. AB - This study was designed to investigate the developmental progression in pencil and crayon grip. The subjects were 320 nondysfunctional children aged 3.0 to 6.11 years, with 20 boys and 20 girls at each 6-month age interval. On the basis of a review of the literature, developmental pencil and crayon grips were defined for the study, and the type of grips each child used to perform a drawing task and a coloring task were recorded. Many children at each age level used mature pencil grips. A developmental progression, however, was shown by the percentage change of children at each age level who used mature grips. Forty-eight percent of the youngest group used mature grips, compared with 90% of the oldest children. Two pencil grips-dynamic and lateral tripod-appear to be common in older children. Differences in the developmental progression of pencil grip were noted between boys and girls and between a drawing task and a coloring task. PMID- 2248352 TI - Activity patterns and life changes in people with depression. AB - The Activity Pattern Indicator (API) (Diller, Fordyce, Jacobs, & Brown, 1978) and the Schedule of Recent Experience (SRE) (Holmes, 1981) were used to determine activity patterns and life changes for 15 depressed patients admitted to an acute care mental health unit. Eight categories on the API were correlated with six categories on the SRE to determine the relationship between activity patterns 1 week and 1 month before hospitalization and life changes for the past year. Two correlations indicated that as the total number of life changes and home and family life changes increase, activity related to personal care decreases. Other correlations showed that as life changes related to health, work, and finance increase, such activities as passive recreation, homemaking, socializing, and personal care also increase. Because activity is the cornerstone of occupational therapy, occupational therapists, in treating patients with depression, might include facilitating close inspection of the patients' activity patterns in relation to the changes that have occurred in their lives. PMID- 2248353 TI - Concurrent validity of the task-oriented assessment component of the Bay Area Functional Performance Evaluation with the American Association on Mental Deficiency Adaptive Behavior Scale. AB - This study was designed to test the concurrent validity of the revised Task Oriented Assessment (TOA) component of the Bay Area Functional Performance Evaluation (BaFPE) (Bloomer & Williams, 1979) with Part 1 of the American Association on Mental Deficiency Adaptive Behavior Scale (ABS) (Nihira, Foster, Shellhaas, & Leland, 1969, 1974) and to develop a means of interpretation for the numeric scores on the TOA. Both measures were administered to 67 psychiatric inpatients within the first 14 days of admission. Low to moderate correlations were found between the TOA tasks and functional parameters and the ABS domains. Because the TOA shows low concurrent validity with the ABS, only limited interpretive descriptions for TOA scores could be developed. PMID- 2248354 TI - Effects of continuous passive motion and elevation on hand edema. AB - The purpose of this study was to evaluate the efficacy of the use of continuous passive motion (CPM) of the digits in combination with limb elevation to reduce hand edema. The effects of 30 min of CPM of the digits with the limb elevated were compared with the effects of 30 min of limb elevation alone. Each of 16 subjects with hand edema of varied etiology received both treatments, one on each of 2 consecutive days. Measures of hand volume, finger circumference, and finger stiffness were taken before and after each treatment. Analyses comparing mean percentage change scores for both treatments showed large and significant treatment effects for all three dependent measures. The findings indicate that, for this sample, CPM with limb elevation was a more effective treatment for the reduction of hand edema than limb elevation alone. The results of analyses performed on a subgroup of 11 subjects with hemiplegia were similar, thus suggesting that CPM with limb elevation may be an effective method by which to reduce hand edema for this patient population. PMID- 2248355 TI - An adjustable splint for forearm supination. AB - The adjustable supination splint is used in select cases in which traditional mobilization therapy is not productive in supination gains. The success of the splint varies depending on many factors, including the type and severity of the injury; the timing of the intervention; the patient's age; and the patient's tolerance of and compliance with the treatment program. The therapist must consult with the physician and have his or her approval before initiating the treatment regimen. Splint use is contraindicated in patients with unstable fractures or with injuries that require surgical intervention before splinting. Therapists should watch for edema, pain, and neurological changes. Depending on the severity of these symptoms, the splint may need to be discontinued or the wearing time and tension adjusted. In our experience at Union Memorial Hospital and in our weighing of the above considerations, we have found favorable results in the use of the adjustable supination splint, with gains in range of motion and function in select patients. PMID- 2248356 TI - The new direction in health policy. PMID- 2248357 TI - Book on AIDS missing from special issue. PMID- 2248358 TI - Special issue on AIDS is a substantial contribution. PMID- 2248359 TI - In bed together at the market: psychiatry and the pharmaceutical industry. PMID- 2248360 TI - The readiness of health profession students to comply with a hypothetical program of forced migration of a minority population. AB - The readiness of Jewish Israeli medical, psychology, and social work students to cooperate in a hypothetical government program involving expulsion of Arabs from Israel was explored via research scenarios that pointedly used terms reminiscent of Holocaust events. Strong moral sensitivity was expected on the part of the study subjects as both Jewish Israelis and vocationally committed to human welfare. The authors argue that the readiness of as many as one-third of the sample to "follow orders" is a disturbing sign, calling for greater vigilance in defense of human rights and values. PMID- 2248361 TI - The psychological impact of the Intifada on Palestinian children in the occupied West Bank and Gaza: an exploratory study. AB - The mental health of 796 Palestinian children living in the occupied West Bank and Gaza Strip was assessed in terms of reported psychological status and behavioral symptoms. Results, interpreted within the context of the 1987 uprising (Intifada), indicate that exposure to political and military violence may be associated with the onset of conduct problems and fears, although active participation in the conflict may enhance self-esteem and shield children from development of psychological symptoms. PMID- 2248362 TI - Identification patterns of offspring of Holocaust survivors with their parents. AB - The patterns of identification with their parents of a sample of children of Holocaust survivors showed clear differences from those of a control group. As the clinical literature would indicate, these differences suggest a specific character organization rather than psychopathology. An explanation for the lack of agreement on this issue in the empirical literature is proposed and explored. PMID- 2248363 TI - The role of the father in the development of stranger sociability during the second year. AB - The relationship between quality of infant attachment to parents and sociability toward a strange adult was investigated, and level of stranger sociability with father present was compared to that with mother present. Results suggest that during the child's second year, and particularly for boys, the presence of the father represents a distinct social context for the child. PMID- 2248364 TI - Children and their fathers after parental separation. AB - This two-year longitudinal study of 121 6-12-year-old children in the custody of their mothers following parental separation examined main and interacting effects of child's age and gender, frequency and regularity of visitation, father-child closeness, and parental legal conflict on children's self-esteem and behavioral adjustment at two time points. Predictors were found to have different implications for different groups of children and for children in different situations. Findings suggest the futility of seeking simple answers to whether ongoing contact with fathers following divorce is beneficial or detrimental for children. PMID- 2248365 TI - The effects of marital disruption on adolescents: time as a dynamic. AB - As part of an ongoing ten-year longitudinal research project, 382 15-year-olds from a white, working-class community were studied. Findings indicate that those who experienced parental separation more recently were most likely to be adversely affected, and that girls from recently disrupted families were more likely than boys to experience problems in emotional and behavioral functioning and were likely to express dissatisfaction with available levels of social support. PMID- 2248366 TI - A comparison of stepfamilies with and without child-focused problems. AB - Stepfamilies in therapy for a child-focused problem were compared to those without such a problem and not in therapy. Differences were found in reciprocity within the stepparent-stepchild relationship, satisfaction with the stepparent's role, level of stepfamily conflict, and degree of stepfamily expressiveness. Results are discussed in terms of current research and clinical implications. PMID- 2248367 TI - Perceptions of parental competence while facing the death of a spouse. AB - Healthy parents' perceptions of their competence to meet children's needs during the terminal illness of the other parent were measured on five major domains of parent-child relationships and parental functioning central to children's healthy development. Significant declines from pre-illness competence were perceived, of which the greatest were in emotional sensitivity and responsiveness, and ability to set limits and impose discipline. Implications for the development of preventive intervention strategies are discussed. PMID- 2248368 TI - Characteristics of unmarried adolescent mothers: determinants of child rearing versus adoption. AB - The sociodemographic and biographical characteristics of a group of unmarried adolescent mothers who opted to rear their children were compared with those of a matched group who placed their children for adoption. Those choosing adoption were more likely to be of higher socioeconomic status, to have higher educational aspirations, and to be from suburban residences. Suggestions for intervention and appropriate services are offered. PMID- 2248369 TI - Predicting success in foster placement: the contribution of parent-child temperament characteristics. AB - Parent and child temperament variables were examined in an interactive "goodness of fit" model with respect to foster placement outcome. The "mismatch" of a rigid foster mother and a child of negative mood was found to be predictive of less successful placement outcome, as was the placement of a child of more negative mood than expected by the foster mother. PMID- 2248370 TI - Children from disrupted and adoptive homes on an inpatient unit. AB - Among 375 children and adolescents admitted to a psychiatric hospital inpatient unit, the proportion of adopted children was considerably higher than that of a general pediatric population or of census figures, and the majority of nonadoptees were from disrupted homes. Based on a review of case records, adoption and family disruptions appear to increase significantly the length of hospitalization and to shift diagnoses toward behavioral disturbances. Implications for prevention and treatment are considered. PMID- 2248371 TI - Gender, coping, and psychological well-being in spouses of older adults with chronic dementia. AB - Relationships among gender, types of coping strategies, and psychological well being were examined in 61 spousal caregivers of older adults with chronic dementia. Gender emerged as a significant correlate of well-being (with women reporting higher levels of distress), although not of related coping strategies. Implications for research into interactions among biological, psychological, and social factors contributing to women's psychological distress are discussed. PMID- 2248372 TI - Nuclear freedom and students' sense of efficacy about prevention of nuclear war. AB - Questionnaire and interview responses of young New Zealanders, living in a nuclear-free zone, reveal general concerns about nuclear war but relatively little personal, subjective worry. Their sense of citizen and national efficacy is stronger than that reported by youngsters in other countries, but is not reflected in feelings of self-efficacy. Responses are compared to those reported in North American and European research, and the importance of adult role models in facilitating children's belief in the efficacy of antinuclear activities is highlighted. PMID- 2248373 TI - A reappraisal of the anatomical basis for speech in Middle Palaeolithic hominids. AB - The recovery of a fossil hominid skeleton with a complete hyoid bone from Mousterian deposits in Kebara Cave, Israel, provides new evidence pertaining to the evolution of speech. Previous studies of speech in the Middle Palaeolithic (most notably those on Neandertals) have focused on the basicranium as an indicator of speech capabilities. This work critiques the use of the basicranium and instead presents the anatomical relations of the hyoid and adjacent structures in living humans as a basis for understanding the form of the vocal tract. The size and morphology of the hyoid from Kebara and its relations to other anatomical components are almost identical to those in modern humans, suggesting that Middle Palaeolithic populations were anatomically capable of fully modern speech. PMID- 2248374 TI - Neandertal scapular glenoid morphology. AB - Analysis of Neandertal and recent human scapular glenoid fossae reveals that the former had long, narrow, and flat glenoid articular surfaces relative to those of modern humans. Comparison of glenoid length, breadth, and curvature to humeral articular dimensions demonstrates that Neandertal glenoid length and curvature scale to proximal and distal humeral articular dimensions in the same manner as those of modern humans. The remaining contrast is in the relatively greater glenoid fossa width seen in modern humans. This difference in morphology implies differences in the habitual degree of dorsoventral glenohumeral movement between Neandertals and modern humans. This in turn may be related to contrasts in tool use, especially with respect to throwing and projectile use. PMID- 2248375 TI - Continuous-variable quantification of dermatoglyphic whorl patterns: a statistical study of angular measurements. AB - Core(s) and triradii of dermatoglyphic whorl patterns were joined together to form triangles. Base angles of these triangles were measured (in degrees). The tangent angle at the lower edge of a ridge crossing the core-triradius line was also measured in degrees on each side of the whorl. Significant differences and similarities of these angles were investigated for unrelated Caucasian males and females by the use of Student's t- and Pearson's r-tests. Angular findings were related to the corresponding information provided by ridge counts. Similarities and differences between males and females are described. PMID- 2248376 TI - A quantitative investigation of irregular cuspules in human maxillary permanent molars. AB - The frequency of occurrence of anomalous cusps or tubercles on human upper first molars was investigated in seven racial populations using moire contourography, which permits the three-dimensional measurement of minute cusps. Tubercles on the mesial marginal ridge were more frequently found in Mongoloid populations (Japanese and Eskimo) than in others. The frequency of the protoconule was high in Eskimos and Negroids (Bantu and San). The lingual paracone tubercle (mesial cusp) showed a particularly high frequency in Australian aborigines. The metaconule was rare or absent in all of the populations. Caucasoid groups (Dutch White and Asiatic Indian) showed generally low frequencies of all these abnormal tubercles, especially the distal accessory cusp (C5). Racial differences in the frequencies of occurrence may offer a key to understanding the adaptive significance of these traits and human microevolution. Confusion in nomenclature for upper molar tubercles is also discussed. PMID- 2248377 TI - The choice of a statistic for testing hypotheses regarding seasonality. AB - This paper discusses statistical methods for testing hypotheses of seasonality in births across one year, using monthly frequencies. It argues that the Freedman test, a variant of the Kolmogorov-Smirnov one-sample test, and the Edwards test and its modifications are most appropriate for this purpose. These tests take into account the order of the monthly frequencies and have a higher power than the ordinary chi-square goodness-of-fit test, regarding seasonality. The paper addresses some points mentioned in earlier papers by McCullough, and O'Brien and Holbert. PMID- 2248379 TI - Effects of speed on forelimb joint angular displacement patterns in vervet monkeys (Cercopithecus aethiops). AB - Shoulder, elbow and wrist joint angular displacement patterns were analyzed for five vervet monkeys across increasing speed. Within symmetrical gaits, the peak positions of the pattern for each joint tended to decrease with increasing speed as did the yield angle of the elbow (more "yielding"). Across the walk(run) gallop transition there were no notable changes in the displacement patterns, but there was a consistent decrease in the range of elbow movements and an increase in the yield angle. Across symmetrical gaits, there was also a tendency for some of the peak positions to decrease. These results are compared with those available for cats and dogs, and are interpreted relative to functional and neurological aspects of forelimb movements in primates. PMID- 2248378 TI - Birth spacing patterns in humans and apes. AB - Comparative studies of birth interval dynamics in wild primates suffer from several problems of analysis and interpretation: (1) the data are always right censored, (2) sample sizes are usually small, (3) the distribution of birth intervals is expected to be non-normal, (4) early offspring mortality is a confounding variable, and (5) differences in life history (e.g., presence or absence of menopause) can complicate interpretation of the results. A survival analysis designed to minimize these problems is applied to published data on wild chimpanzees and gorillas from Gombe and Virunga Parks, respectively, and to new data on wild orangutans from Tanjung Puting National Park and on a human population, the Gainj of highland Papua New Guinea. According to this analysis, the estimated median birth interval (when the offspring whose birth opens the interval does not die within the interval) is 43.3 +/- 1.0 months for the Gainj, 45.5 +/- 1.2 months for gorillas, 66.6 +/- 1.3 months for chimpanzees, and 92.6 +/- 2.4 months for orangutans. PMID- 2248380 TI - Age- and sex-associated variations in the directional asymmetry of rhesus macaque forelimb bones. AB - Several investigators have questioned the significance of handedness as an explanation of directional forelimb asymmetries, yet little has been done to isolate other explanatory factors. In this investigation, we analyze 61 female and 76 male rhesus macaque skeletons for evidence of age- and/or sex-associated variations in ten forelimb bone measurements. All significant directional asymmetries are found to favor the right side. Although some of these asymmetries are found to favor the right side. Although some of these asymmetries are compatible with the interpretation of muscle hypertrophy associated with preferential use of the right forelimb, the overall pattern suggests that age- and sex-related ontogenetic factors deserve equal consideration. Significant sex differences in asymmetry means are present within and across age groups (juveniles, subadults, and adults), and numerous changes in asymmetry with age are also found. A pattern of decreasing asymmetry with age was found in males, with 40% of the ten measures being asymmetrical in juveniles, 30% in subadults, and 20% in adults. Among females, this pattern is reversed. No significant asymmetries were found for juvenile or subadult females, whereas 40% of the measures were asymmetrical in adult females. We conclude that greater consideration of age- and sex-related factors is necessary when drawing samples for the purpose of investigating asymmetries, and an awareness of trait-specific age and sex patterns of variation is necessary when citing forelimb asymmetries in demographically nonrepresentative populations as evidence of handedness or other behavioral asymmetries. PMID- 2248381 TI - Occlusal force and craniofacial biomechanics during growth in rhesus monkeys. AB - The masticatory muscles in 132 anesthetized male and female rhesus monkeys ranging in age from juvenile to adult were unilaterally stimulated. Muscle forces and speeds were measured with a bite force transducer positioned at the incisors, premolars, and molars during twitch and tetanic contractions. Lateral cephalographs of all animals were used to estimate the orientation and mechanical advantage of the masticatory muscles. Results showed that maximal occlusal forces increased at a greater rate than body weight during growth. However, maximal occlusal forces increased isometrically relative to mandibular length. Mean forces at the incisors ranged from 70.3 newtons (n) in juveniles up to 139.9 n in adult males. Forces at the molars were 2-2.5 times greater than at the incisors. Time-to-peak tension decreased with increasing body size from 44.1 msec in juveniles to 37.4 msec in adult females to 31.0 msec in adult males. Regression analysis showed that adult males have faster muscles than adult females or juveniles even when corrected for body size. Temporalis and masseter orientation was found to change little throughout growth. The mechanical advantage of the masseter and temporalis muscles for producing occlusal forces on the distal molars improved between juveniles and adults, which is contrary to findings of Oyen et al. (Growth 43:174-187, 1979). Among adults, females had a greater mechanical advantage of the masseter muscles than males. PMID- 2248382 TI - Postnatal protein deprivation in rhesus monkeys. AB - We studied the growth of 97 rhesus monkeys (M. mulatta) that from birth until 120 days of age were fed a diet containing 13.4%, 6.7%, 3.35% protein or a commercial simulated human-milk formula (SMA) affording 9% protein. After 120 days, all animals were fed SMA. Females fed the diet lowest in protein, but not the other diets, were moderately affected, gaining less weight than their well-fed counterparts did, but they recovered their deficit during the repletion period, so that at 240 days no group differences remained. Males fed the two lowest protein diets were severely and profoundly affected, in keeping with the depth of their protein deficiency. Moreover, unlike the females, they recovered none of their weight deficit during the repletion period. Food intake during deprivation was lower in the animals eating the low-protein diets. During SMA repletion, intakes followed no simple rule, but they did not converge. Except for the males fed the 3.35% protein diet, relative food intake (ml formula/kg body weight) did not differ substantially between diets or sexes at any time during the deprivation and diminished as the animals got older. Those males' relative intakes did not decline. During repletion, the SMA females ate the most in proportion to weight and the 13.4% group the least. The lowest-protein males, in contrast, ate the most in proportion to their weight during both deprivation and repletion. Males fed the lowest-protein diet gained little for what they ate; those fed the highest-protein diet gained much. Females were more efficient than males were when eating the low-protein diet and less efficient when eating the high-protein diet. When fed SMA during repletion, males' food efficiencies (grams gained/liter of diet) were nearly equal; females still differed: the SMA group was the least efficient and the low-protein group most efficient. Its counterpart, protein efficiency, was greatest (during deprivation) for females eating the low-protein diet and least (among females) for those eating the high protein diet. Males were least protein efficient if eating the low-protein diet. Evidently, a 4 month bout of protein deprivation had prolonged effects on the amount of food the animals needed to produce a given gain in weight. PMID- 2248383 TI - Aging and reproductive performance in langur monkeys (Presbytis entellus). AB - Analysis of data on age and reproductive performance in 16 captive female Hanuman langurs (Presbytis entellus) shows that adult females under the age of 6 years and over the age of 19 years had the lowest rates of reproductive success as measured by the production of viable young that survived beyond 30 days of age. With the possible exception of one female, females over the age of 19 years experienced a variety of idiosyncratic reproductive problems but did not experience a true menopause as defined by total cessation of menstrual cycles. There was no support for the hypothesis that langur monkey females have evolved a lengthy postreproductive period. PMID- 2248384 TI - On ontogenetic and phylogenetic origins of the human chin. PMID- 2248385 TI - Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study. AB - This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248386 TI - Incidence of perioperative myocardial ischemia detected by different electrocardiographic systems. AB - To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.5-30 Hz (a typical operating room monitor), a Marquette Electronics MAC II ECG at 0.05-40 Hz and 0.05-100 Hz (a standard ECG), and a Del Mar Holter recorder at 0.1-100 Hz. Relative ST-segment position and incidence of new ischemia compared to the preoperative ECG were determined in 109 sets of preinduction traces and 877 sets of intraoperative traces. ST-segment position on the three recording systems conforming with the American Heart Association (AHA) low-frequency response recommendations (0.05 Hz) were similar. Compared to the standard ECG, ST-segment position on the Spacelabs at 0.5-30 Hz was consistently more negative. Displacement on the Holter was consistently less negative and less positive. By the 0.1-mV displacement criterion for diagnosis of myocardial ischemia on any one ECG system, 16.5% of patients on arrival and 32.1% of patients intraoperatively suffered new myocardial ischemia. Based on the operating room monitor, arrival and intraoperative ischemia were present in 15.6 and 27.5% of patients, respectively. Ischemia at the same periods was less frequent by the standard ECG system (5.5 and 12.8%, respectively) and least frequent by the Holter recorder (4.6 and 8.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248387 TI - Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy. AB - Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248388 TI - Pharmacokinetics of fentanyl administered by computer-controlled infusion pump. AB - Fentanyl was administered to 21 patients using a computer-controlled infusion pump (CCIP) based on a pharmacokinetic model. Eleven of the patients were dosed according to the pharmacokinetics described by McClain and Hug, and ten of the patients were dosed according to the pharmacokinetics described by Scott and Stanski. The authors measured the difference between the measured arterial fentanyl concentrations and the concentrations predicted by the CCIP for each pharmacokinetic parameter set. The median absolute performance error (MDAPE) in patients dosed according to McClain and Hug's parameters was 61%, and the MDAPE in patients dosed according to Scott and Stanski's parameters was 33%. The population pharmacokinetics in these 21 patients were analyzed using a pooled data technique. The pharmacokinetics of fentanyl in this population showed a smaller central compartment volume and a more rapid initial distribution half life than previously estimated for fentanyl. The derived pharmacokinetic parameters described these patients well and also predicted the observed fentanyl concentrations from four previously published fentanyl studies with reasonable accuracy. Comparison of the parameters used by the authors with those of McClain and Hug demonstrated that dosing regimens designed from pharmacokinetic models can be fairly accurate at the times sampled in the original study but may not be accurate at time points not sampled in the original research. The authors concluded that although the pharmacokinetics of fentanyl administered by CCIP are the same as the pharmacokinetics of fentanyl administered by a bolus or constant rate infusion, a pharmacokinetic study using a CCIP may be particularly effective at characterizing the most rapid distribution pharmacokinetic parameters, and thus may provide parameters appropriate for subsequent use in a CCIP. PMID- 2248389 TI - Long-term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in the elderly. AB - This study compared the effects of general and regional anesthesia on cognitive and psychosocial functioning in elderly persons. Sixty-four patients between 60 and 86 yr of age undergoing knee arthroplasty were randomly assigned to receive either general or regional anesthesia. A battery of psychometric tests, including the Satz-Mogel form of the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised and the Sickness Impact Profile, and various neuropsychological measures were administered by a blinded observer just before surgery and again 3 months later. Analyses of covariance revealed improvements in most measures that were equivalent between groups. The results indicated that there were no cognitive or psychosocial effects of general or regional anesthesia after 3 months in elderly persons undergoing knee arthroplasty. In this patient population, general anesthesia poses no more risk to long-term mental function than regional anesthesia. PMID- 2248390 TI - Neonatal patterns of breathing after cesarean section with or without epidural fentanyl. AB - The pattern of breathing and lung mechanics were evaluated during the first 7 h of life in full-term healthy newborns delivered by cesarean section with bupivacaine epidural anesthesia, without (group 1) or with the addition of 100 micrograms of fentanyl (group 2). Respiration and oxyhemoglobin saturation (SpO2) were measured with calibrated inductive plethysmography and pulse oximetry, respectively, and recorded from 60-420 min following birth. Compliance of respiratory system (CRS) was measured using a multiple occlusion technique at 60 and 420 min. Pattern of breathing was compared during period I (60-240 min) and II (240-420 min) with the following results: 1) the number of apnea spells was similar in both groups during both periods; 2) in both groups, from period I to period II a significant decrease in apnea duration was observed (7.6 +/- 0.7 s 4.1 +/- 0.5 s in group 1 and 6.7 +/- 1.2 s-5.1 +/- 1.0 s in group 2, respectively (P less than 0.05); 3) respiratory rate (RR) and minute ventilation (VE) were similar in both groups during both study periods; and 4) both RR and VE significantly decreased in the two groups from period I to period II (i.e., 59 +/ 5-46 +/- 2 breath per min-1 and 313 +/- 60-248 +/- 24 ml.kg-1.min-1 in group 1, and 60 +/- 2-51 +/- 1 breath.min-1 and 318 +/- 12-290 +/- 12 ml.kg-1.min-1 in group 2, respectively; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248391 TI - The thermoregulatory threshold in infants and children anesthetized with isoflurane and caudal bupivacaine. AB - Hypothermia in anesthetized adults provokes centrally mediated, peripheral thermoregulatory vasoconstriction at threshold temperatures approximately 2.5 degrees C below normal. The weight dependence of thermoregulatory vasoconstriction was evaluated in 33 unpremedicated pediatric patients receiving isoflurane/oxygen anesthesia (end-tidal concentrations approximately 0.9%) and caudal anesthesia with bupivacaine. The patients were prospectively assigned to four weight groups (5-10 kg, 10-20 kg, 20-30 kg, and 30-50 kg). Central temperature was measured at the tympanic membrane, and average skin surface temperature was determined from four cutaneous sites; mean body temperature was calculated from central and average skin temperatures. Finger blood flow was determined using laser Doppler flowmetry and forearm-fingertip skin temperature gradients. Significant peripheral vasoconstriction was prospectively defined as a laser Doppler flow index 50% of the value recorded 10 min after induction of anesthesia. Thermoregulatory thresholds were defined as the tympanic membrane or mean body temperatures at which significant vasoconstriction occurred. Vasoconstriction occurred in 32 of the patients at temperatures ranging from 34.4 to 35.3 degrees C. Central and mean body threshold temperatures did not differ among the groups, and were similar to those observed previously in adults. There was a good correlation between laser Doppler flowmetry and forearm-fingertip skin temperature gradients in individual patients. PMID- 2248392 TI - Determinants of systolic and diastolic flow in coronary bypass grafts with inotropic stimulation. AB - Using implanted pulsed Doppler microprobes sutured on saphenous bypass grafts in ten patients we studied, 6 h after cardiac surgery, the effects of 5 and 10 micrograms.kg-1.min-1 of dobutamine on mean (Qm), systolic (Qs), and diastolic (Qd) coronary bypass graft flows, as well as on coronary systolic (integral of Qs) and diastolic (integral of Qd) blood volumes entering the myocardium per cardiac beat. Qm increased during the inotropic stimulation from 61.8 +/- 19.2 to 81.1 +/- 21.8 ml.min-1 (P less than 0.001) and resulted from an unchanged Qs and from a large increase in Qd (P less than 0.01). Qd increased more than did diastolic arterial pressure and was related to rate pressure product taken as an index of myocardial oxygen consumption (r = 0.76, P less than 0.001). Despite the dobutamine-induced increase in heart rate (P less than 0.01), integral of Qs, and integral of Qd, the systolic and diastolic inflow volumes per cardiac beat were unchanged. We conclude that increased myocardial blood supply through the saphenous vein bypass graft during inotropic stimulation by dobutamine resulted from different systolic and diastolic events. The oxygenated blood volume entering the coronary vascular bed per beat was unchanged despite tachycardia. PMID- 2248393 TI - Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. AB - We undertook a retrospective chart review of 37 neonates who received fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation (ECMO) between May 1986 and October 1988. We quantified the doses of all sedatives utilized, determined the incidence of neonatal abstinence syndrome (NAS), and identified risk factors associated with NAS. We determined peak fentanyl infusion rate, mean fentanyl infusion rate, total fentanyl dose, and duration of ECMO therapy. NAS was observed in 21 of 37 neonates (57%). In both the NAS and non-NAS neonates, mean infusion rate increased steadily during ECMO therapy, from a mean of 11.6 +/- 6.9 (SD) micrograms.kg-1.h-1 on day 1 to a mean of 52.5 +/- 19.4 (SD) micrograms.kg-1.h-1 by day 8. Total fentanyl dose and duration of ECMO were significantly greater in neonates with NAS. We found that neonates with a total dose greater than 1.6 mg/kg or an ECMO duration greater than 5 days had a significantly greater incidence of NAS (chi-squared test, P less than 0.01 and P less than 0.005; odds ratios = 7.0 and 13.9, respectively). With multiple logistic regression, ECMO duration was found to be the most powerful predictor of the occurrence of NAS. We also measured plasma fentanyl concentrations in a separate group of 5 neonates receiving fentanyl by continuous infusion for sedation. Fentanyl concentrations increased steadily during the period of infusion, suggesting the development of tolerance to the sedating effects. We conclude that continuous administration of fentanyl for sedation is associated with the uniform development of tolerance and a significant incidence of dependence. Alternative approaches to sedation should be investigated. PMID- 2248394 TI - The inhibitory action of halothane on reflex constriction in mesenteric capacitance veins. AB - Potent inhalational anesthetics depress autonomic reflex responses at multiple sites. Most studies emphasize cardiac chronotropic changes and changes in systemic blood pressure. Recently, active reflex venoconstriction of 500-1,000 microns O.D. mesenteric veins has been demonstrated. In the current study, the effects of halothane on the reflex responses of similar mesenteric veins were measured. Mesenteric vein diameter and intravenous pressure were measured in 500 1,000 microns O.D. veins from the mesentery of segments of terminal ileum externalized in situ from 27 New Zealand white rabbits anesthetized with alpha chloralose. Mean arterial pressure was measured with femoral arterial cannulation, and heart rate was determined from the arterial pressure signal. In a separate group of six animals, sympathetic efferent nerve activity was measured from a postganglionic splanchnic nerve. Reflex venoconstriction and increases in mean arterial pressure and mesenteric vein pressure in response to bilateral carotid occlusion were attenuated by 0.5% and 1% inhaled halothane but not by superfusate equilibrated with 3% halothane. Decreases in mesenteric vein diameter and increases in mesenteric vein pressure in response to celiac ganglion stimulation were unaffected by both 0.5% inhaled halothane and superfusate equilibrated with 5% halothane. The bilateral carotid occlusion reflex-mediated increase in sympathetic efferent nerve activity was depressed by both 0.5% and 1% inhaled halothane. The effect of inhaled halothane on prestimulation baseline vein diameter was inconsistent. Superfusate equilibrated with 5% but not 3% halothane caused baseline venodilation. These results suggest a mechanism whereby control of venous tone is inhibited by halothane proximal to the postganglionic neuron. This could involve central or ganglionic inhibition. PMID- 2248395 TI - Subarachnoid clonidine reduces spinal cord blood flow and glucose utilization in conscious rats. AB - The authors investigated the spinal blood flow and metabolic effects of subarachnoid clonidine in conscious rats prepared with chronically implanted subarachnoid catheters. For the blood flow experiments, rats received saline (n = 7) or clonidine 20 nmol (7 micrograms; n = 6), 100 nmol (27 micrograms; n = 5), or 400 nmol (107 micrograms; n = 7) intrathecally. Another group of rats received clonidine 400 nmol intravenously (n = 4). Spinal glucose utilization was measured in rats that received either saline (n = 5) or clonidine 100 nmol (n = 5) intrathecally. Spinal cord blood flow (SCBF) and glucose utilization were measured in five gray and three white matter areas of lumbar spinal cord 15 min after drug administration with the autoradiographic iodo-[14C]-antipyrine and 2 [14C]-deoxyglucose methods, respectively. Physiologic differences between the groups were minor. Rats in the blood flow experiments that received clonidine 100 nmol had a slightly lower arterial PO2 level (70 +/- 1 vs. 82 +/- 3 mmHg; P less than 0.05), whereas those in the glucose utilization group were mildly hypocarbic (PCO2 27 +/- 1 vs. 32 +/- 2 mmHg; P less than 0.01) relative to control animals. Only animals that received 400 nmol clonidine intrathecally had significant analgesia, as assessed by the tail-flick test. One control animal for the metabolism experiments was technically unsatisfactory and was excluded from data analysis. Subarachnoid clonidine reduced both SCBF and glucose utilization. In spinal gray matter, the largest decreases in flow (32-44%; P less than 0.01) occurred with 20 nmol clonidine, whereas flow decreased least (12-27%) with the 400-nmol dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248396 TI - Halothane alters the oxygen consumption-oxygen delivery relationship compared with conscious state. AB - The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2. PMID- 2248397 TI - Covalent binding of oxidative biotransformation intermediates is associated with halothane hepatotoxicity in guinea pigs. AB - In vivo covalent binding of halothane biotransformation-reactive intermediates to hepatic protein and lipid was examined in association with the subsequent development of hepatic necrosis in the guinea pig. Oxidative halothane biotransformation was inhibited by the use of deuterated halothane, whereas reductive metabolism was enhanced by low inspired oxygen concentrations. Male outbred Hartley guinea pigs (n = 8) were exposed to either 1% (v/v) halothane or deuterated halothane--with a fractional inspired O2 concentration (FIO2) of 0.40 or 0.10--for 4 h. Livers removed from half of the animals immediately after anesthesia were evaluated for organic fluorine bound to protein and lipid. The remaining animals were evaluated for a hepatotoxic response up to 96 h after exposure. Only guinea pigs that received 1% halothane at an FIO2 of 0.40 had centrilobular necrosis develop with significantly increased plasma alanine aminotransferase activities. All other treatment conditions significantly reduced oxidative halothane biotransformation, as indicated by decreased plasma trifluoroacetic acid concentrations. These reductions were associated with a significant decrease in organic fluorine bound to hepatic proteins. An FIO2 of 0.10 during halothane anesthesia significantly enhanced reductive biotransformation, as indicated by plasma fluoride ion concentrations. This was associated with a significant increase in organic fluoride bound to hepatic lipids. Centrilobular necrosis did not develop under these conditions. Thus, covalent binding to subcellular proteins by the trifluoroacetyl acid chloride intermediate generated by oxidative halothane biotransformation is implicated as a mechanism of centrilobular necrosis in guinea pigs. Binding to lipids by reductive pathway generated free radicals does not appear to be involved in production of the lesion. PMID- 2248398 TI - Morphine and alfentanil permeability through the spinal dura, arachnoid, and pia mater of dogs and monkeys. AB - Little information exists about which spinal meninx is the principal permeability barrier between the epidural space and the spinal cord or about what physicochemical properties of drug molecules govern their meningeal permeability. To better understand these aspects of epidural pharmacokinetics, the authors measured the permeability of morphine and alfentanil through the different components of the spinal meninges-dura mater, arachnoid mater, and pia mater-of dogs and monkeys in vitro. Live meningeal tissue from either species (dura mater alone, pia mater alone, or intact dura-arachnoid-pia) was placed between two fluid reservoirs of a temperature-controlled diffusion cell. The permeability of the tissues to each opioid was determined by placing the opioid in one of the reservoirs of the diffusion cell and measuring the rate at which the drug diffused through the tissue and appeared in the second reservoir. The arachnoid mater was found to be the major meningeal diffusion barrier between the epidural space and the spinal cord. Alfentanil was 3.7 times more permeable than morphine through all three meninges, suggesting that increased lipid solubility increases meningeal permeability. However, neither lipid solubility nor molecular weight adequately explained the difference in permeability between morphine and alfentanil. The authors conclude that this in vitro model has significant utility for studies aimed at predicting in vivo meningeal permeability and hence the potency and rapidity of action of any opioid administered by the epidural route. PMID- 2248399 TI - Effects of nitrous oxide on contractile function and metabolism of the isolated heart. AB - Nitrous oxide has a long clinical history, but its effects on the heart remain controversial. The direct effects of N2O on global myocardial function have not been reported. The authors' aim was to examine the inotropic, chronotropic, dromotropic, and vascular effects of N2O, compared with its N2 control, on hearts isolated from the guinea pig. Hearts (N = 31) were isolated and perfused at 37 degrees C with Krebs-Ringer solution at constant pressure. Isovolumetric left ventricular pressure (LVP) and its derivative (maximum rate of tension development [dP/dtmax]) were measured by placing a saline-filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurement of heart rate (HR) and atrioventricular conduction time (AVCT). The venae cavae were ligated, and the right ventricle was cannulated through the pulmonic valve to collect coronary sinus effluent for measurement of coronary outflow O2 tension, adenosine, and inosine. After stabilization and perfusion with 96% O2 (plus 4% CO2), each heart was exposed for 10 min either to 48% N2O or to 48% N2 with 48% O2. After repeated perfusion with 96% O2 for 10 min, hearts were exposed in the reverse order to 48% N2O or 48% N2. In the postcontrol period, hearts were again exposed to 96% O2. Inflow Po2 (in mmHg) was 506 +/- 5 (standard error of the mean [SEM]) during 96% O2 and 258 +/- 5 during both 48% N2 and 48% N2O. Effluent Po2 was 155 +/- 7 during 96% O2, 81 +/ 5 during 48% N2, and 83 +/- 5 during 48% N2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248400 TI - Alterations in brain electrical activity may indicate the onset of malignant hyperthermia in swine. AB - The time course of changes in brain electrical activity during halothane anesthesia was examined in 12 malignant hyperthermia-susceptible (MHS) and 14 normal (nMHS) swine. Power densities in selected frequency bands were calculated from the electroen-cephalogram (EEG). EEG and systemic variables were determined over a period of 60 min after starting halothane (1% inspired). Malignant hyperthermia (MH) was triggered in all susceptible pigs. Initial changes in the EEG during development of MH consisted of a decrease in total power and a shift to lower frequencies (delta-theta activity) in all animals. These EEG alterations were noted when there was an increase in heart rate, but other systemic variables were still normal. EEG changes in all MHS animals started at an arterial oxygen tension (PaO2) greater than 90 mmHg and an arterial carbon dioxide tension (PaCO2) less than 50 mmHg. In 5 MHS animals EEG became isoelectric at a PaO2 of 61-82 mmHg and a PaCO2 of 53-68 mmHg. Mean arterial blood pressure at this time was 54-66 mmHg. To determine the effects of hypoxia on the EEG in 7 nMHS animals, oxygen was decreased over a period of 45-60 min to 7% inspired. In 7 other nMHS animals, hypercarbia was produced by admixture of carbon dioxide to the fresh gas supply to achieve incremental increases of PaCO2 to 110-120 mmHg. Significant EEG changes during hypoxia comparable to those seen at the onset of MH were noted at a PaO2 below 40 mmHg and during hypercarbia at a PaCO2 greater than 68 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248401 TI - Effect of halothane and isoflurane on postischemic "stunned" myocardium in the dog. AB - Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic "stunned" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248402 TI - Paraben preservatives but not succinylcholine are cerebral vasodilators in vitro. AB - Since the increase in intracranial pressure produced by succinylcholine is temporally associated with intravenous administration, we investigated in vitro a possible direct cerebrovascular effect of this nicotinic drug. Isometric responses were recorded from dog and guinea pig basilar artery rings suspended in modified Krebs' solution at 37 degrees C. After precontracting with a voltage (KCl)- or a receptor (5-hydroxytryptamine)-mediated agonist, cumulative concentration-relaxation curves were established for: pure succinylcholine; Quelicin from multidose vials containing 20 mg/ml succinylcholine, 1.8 mg/ml methylparaben, and 0.2 mg/ml propylparaben; Anectine from single-dose vials containing 20 mg/ml succinylcholine; multidose Anectine containing 20 mg/ml succinylcholine and 1.0 mg/ml methylparaben; and methylparaben and propylparaben alone. When required, the endothelium of dog artery was removed by gentle mechanical rubbing and the response to the drugs reevaluated. Both Quelicin and multidose Anectine produced statistically significant (P less than 0.05) relaxation; Quelicin was the more potent of the two. Methylparaben and propylparaben produced relaxation in an additive manner and completely accounted for the relaxation produced by Quelicin and multidose Anectine. The vascular relaxation was found to be independent of the presence of a functional endothelium. Consistent with a nicotinic induced contraction, pure succinylcholine maintained vessel tone. It is concluded that the pharmaceutically ubiquitous preservatives methylparaben and propylparaben but not pure succinylcholine have vasoactive properties in vitro. PMID- 2248403 TI - And the patient chose: medical ethics and the case of the Jehovah's Witness. PMID- 2248404 TI - Metered dose inhaler aerosol characteristics are affected by the endotracheal tube actuator/adapter used. AB - The authors studied the particle size of aerosols of metaproterenol produced by three different actuators designed for use in patients with endotracheal tubes in place. These were compared with the metaproterenol aerosol produced by the actuator (provided by Boehringer-Ingelheim [BI]) that was supplied by the manufacturer for use in patients whose tracheas are not intubated. The volume of particles in the respiratory size range (1.0-5.1 microns) delivered to the end of the endotracheal tube were measured using adapters designed by Intec (IT), Instrumentation Industries (II), and Monaghan (MAIS). Particle numbers were measured using a CSAS 100 scattering-aerosol laser spectrometer, and volumes were calculated by assuming the particles were spheres. The authors found that the volume of particles in the respiratory range with the IT, II, and MAIS adapters plus endotracheal tube were 11, 31, and 66%, respectively, of the volume produced in the respiratory range by the BI. When particles likely to impact before reaching the lower airways (greater than 5 microns) were measured, almost none was produced by the adapters plus endotracheal tube, whereas the majority of drug volume in the BI aerosol was in the greater than 5 microns range. It was concluded that the aerosol produced by different actuators differ from each other, that all three produced less drug in the respiratory range than was produced by the manufacturer-supplied actuator, and that large particles are effectively removed by the adapter plus endotracheal tube. PMID- 2248405 TI - Sudden asystole in a marathon runner: the athletic heart syndrome and its anesthetic implications. PMID- 2248406 TI - Airway obstruction in lungs obtained from an asthmatic donor complicating heart lung transplantation. PMID- 2248407 TI - Superior vena cava syndrome as a complication of change in body position during general anesthesia. PMID- 2248408 TI - Anesthetic considerations for severe ovarian hyperstimulation syndrome. PMID- 2248409 TI - Pneumoencephalos after inadvertent intrathecal air injection during epidural block. PMID- 2248410 TI - Tracheal agenesis: resuscitative management. PMID- 2248411 TI - Venous air embolism during hepatic resection. PMID- 2248412 TI - Total spinal anesthesia following early prophylactic epidural blood patch. PMID- 2248413 TI - Knotting of the Theracath after an uneventful epidural insertion for cesarean delivery. PMID- 2248414 TI - Aspiration of meconium from the trachea of neonates. PMID- 2248415 TI - Mechanism of ulnar nerve injury. PMID- 2248416 TI - Improved infection control in the operating room. PMID- 2248417 TI - Sudden cardiac arrest during epidural anesthesia. PMID- 2248418 TI - [Microsurgical approach to the foot arteries in diabetic patients with vascular complications]. AB - This study was made in order to assess the percentage of patients who underwent a by-pass (by saphenous vein) "in situ" on the foot arteries, as an alternative to the amputation for cases of severe ischaemia on the foot. The medium and short term survival associated to the revascularized limb was also analyzed. Sixteen patients underwent this surgical procedure, 8 of them (50%) lost their limb within the following seven days to the revascularization; one patient lost their limb at the first year and 43.7% of patients maintain the viability of their limbs 3 years latter. This surgical procedure was made by microsurgery using a Carl Zeica amplification optic lens 2,3 X and a OFMI microscope with an amplification lens 40 X. PMID- 2248419 TI - [Venous stasis and panniculopathy: a semiologic study]. AB - The relevant role played by the microcirculation on several pathologies and on the genetic evolution of rarely known diseases as the panniculopathy with venous stasis have been explained. It represent a support on the concept for new research of microcirculation's injuries as a primary factor on macrophlebopathies. PMID- 2248420 TI - [Lipedema: clinical and diagnostic criteria]. AB - Lipedema is a common disease in the usual clinical practice. None organic description about the clinical symptoms and signs associated to this condition has been published. Fifty women with lipedema have been examined by the authors, and incidence rates of symptoms and signs have been emphasized. The following signs and symptoms were constantly reported: "Egyptian column", elastic edema, negative Stemmer's sign, alterated plantar support, cutaneous hypothermia. Some others were frequently found: ecchymosis, spontaneous pain, liposclerosis on the thigh, hypodermic hyperalgesia and pain on the internal face of the knee. Moreover, the two most relevant differential diagnosis as well as their two variant's clinical features (mixed lipedema and "thin women" lipedema) have been described. PMID- 2248421 TI - [Capillaroscopic observation in angiologic diagnosis]. AB - The authors present their experience with Morphologic Capillaroscopy, and analyze the diagnostic dates provided by this technique to the current Angiology and Vascular Surgery protocols. Morphologic anomalies founded during diverse systemic diseases as well as the changes on the capillary field produced in cases of chronic ischaemia and venous insufficiency were analysed. The study was made on the basis of 236 capillaroscopic images and it was completed by an extensive bibliographic review of the subject. PMID- 2248422 TI - Intravenous nicardipine: an effective new agent for the treatment of severe hypertension. AB - Fifty-six patients with severe hypertension were treated with intravenous nicardipine for infusion periods of eight to twenty-four hours. Each patient achieved satisfactory blood pressure control during the infusion period with a mean controlling dose of 7.85 mg/hr. The dose of nicardipine needed for sustained blood pressure control correlated with untreated diastolic blood pressure but not with untreated systolic blood pressure. These results demonstrate the potential usefulness of intravenous nicardipine for the treatment of severe hypertension requiring rapid lowering, and they suggest also that the severity of pretreatment diastolic hypertension might be a useful indicator of the dose required for blood pressure control. PMID- 2248423 TI - Calcium antagonists in the management of patients with aneurysmal subarachnoid hemorrhage: a review. AB - Cerebral arterial vasospasm and infarction is the leading cause of death and disability among patients who reach a major medical center after aneurysmal subarachnoid hemorrhage (SAH). Recent evidence suggests that two calcium antagonists, nimodipine or nicardipine, may be useful in preventing this important complication of SAH. This paper reviews the current status of these two calcium antagonists in the management of SAH. PMID- 2248424 TI - Pilot study of nicardipine for acute ischemic stroke. AB - The author performed a pilot study of nicardipine (NC), a Ca(+)+ channel blocker, to study its dosing, toxicity, and possible efficacy for hemispheric cerebral infarction within 12 hours (mean 6.9 hr) of onset to determine the advisability of proceeding with a multi-centered controlled trial. NC was administered IV (3 to 7 mg/hr) X 72 hours by titrating dose to mean arterial blood pressure (MABP not less than 10% of baseline), then orally X 30 days. Forty-three patients have been entered; mean age 63 (range 34-89), 25 male and 18 female. Only 3 had CT evidence of infarct on entry. Results have shown improvement in a 100-point (pt) graded exam (40 pts at entry, 68 pts at 3 months). Of 20 patients completing 3 months' evaluation, 17 improved and none worsened. Sixteen out of 20 were at home and 8 had minimal or no impairment. Mean Barthel's index was 72. Mean maximal serum NC level was 75 ng/mL. MABP decreased from 103 (entry) to 83 (72 hours). A larger controlled study is warranted to determine the efficacy of NC for acute cerebral infarct. PMID- 2248425 TI - Management and clinical use of intravenous nicarpidine. Presented at the 35th annual meeting of the American College of Angiology. Orlando, Florida, October, 1988. Proceedings. PMID- 2248426 TI - Cardiovascular effects of nicardipine. AB - Nicardipine, a new 1-4 dihydropyridine calcium antagonist, has chemical properties that allow oral and stable intravenous preparations. It is the first intravenous dihydropyridine calcium antagonist available in the United States. Among its drug class it has a unique chemical structure that affords properties useful in the treatment of acute cardiovascular conditions, such as myocardial ischemia, congestive heart failure, hypertension, cerebrovascular disease, and other related disorders. In patients with coronary artery disease, intravenous nicardipine has been found to reduce myocardial oxygen demand by reducing afterload and increasing myocardial oxygen supply through coronary vasodilatation. It enhances left ventricular performance and augments coronary blood flow beyond that required by increased myocardial oxygen consumption. Nicardipine may also offer protection from ischemic injury to the heart and central nervous system. Alone and in combination with other antihypertensive agents, nicardipine has been shown to be effective in the treatment of mild to moderate hypertension. It is safe for use in patients with certain types of conduction disturbances because it does not greatly affect sinoatrial and atrioventricular conduction. Additional advantages for nicardipine's use in the management of acute cardiovascular disorders are its rapid onset and short duration of action. PMID- 2248427 TI - An overview of the pharmacology and pharmacokinetics of nicardipine. PMID- 2248428 TI - Postoperative hypertension: a prospective, placebo-controlled, randomized, double blind trial, with intravenous nicardipine hydrochloride. AB - Nicardipine hydrochloride, a new calcium channel blocker for intravenous use, has been compared with placebo in a prospective, randomized, double-blind trial on postoperative hypertension. Of 175 patients who signed preoperative consent, 24 (13.7%) met entry criteria. Hypertension was significantly better controlled in nicardipine-treated patients compared with those receiving placebo (93% versus 30%, p less than 0.05). All the placebo failures were subsequently successfully treated with nicardipine. There were no significant complications in either group. The authors conclude that nicardipine HC1 is an effective, safe therapy for postoperative hypertension. Further studies are now indicated comparing it with other drugs currently used to treat this condition. PMID- 2248429 TI - Prelesional modifications of the vessel wall in hyperlipidemic atherogenesis. Extracellular accumulation of modified and reassembled lipoproteins. PMID- 2248430 TI - Cellular interactions, growth factors, and smooth muscle proliferation in atherogenesis. PMID- 2248431 TI - Electron microscopic exploration of human endothelium in step-serial sections of early and advanced atherosclerotic lesions. AB - A transmission electron microscopic study of step-serial sections of numerous human early and advanced atherosclerotic lesions obtained under conditions preventing artificial endothelial loss was undertaken. It was found that (1) no endothelial denudation with platelet aggregation occurred over any early myoproliferative lesions, (2) endothelial denudation with platelet aggregation had developed only over the mostly necrotic caps of some advanced end-stage lesions, and (3) all stages of atherosclerosis showed endothelial changes that indicated increased permeability of the endothelium over plaques for plasma constituents, namely, opened interendothelial junctions and endothelial lipid inclusions. These results suggest that endothelial denudation and platelet aggregation is not an initiating event in human atherogenesis but something that happens late over the disintegrating surface of some end-stage lesions as a prelude to supra-plaque thrombosis--in agreement with our light microscopic findings of 25 years ago that thrombosis in human atherosclerotic arteries is usually triggered by a breakdown of the mostly necrotic caps of advanced plaques. PMID- 2248432 TI - Arterial metabolism of lipoproteins in relation to atherogenesis. AB - In this short review we have concentrated on the ways in which modification of LDL structure may account for foam cell formation. We have presented in vivo evidence as well as in vitro evidence supporting the proposition that modification of native LDL is a prerequisite for foam cell formation and atherogenesis. Actually, oxidized LDL can contribute to atherogenesis in other ways as well. Oxidized LDL is chemotactic for circulating monocytes, yet inhibits the motility of the tissue macrophage as shown by Quinn et al. Also, oxidized LDL is cytotoxic as discussed above and this could play a crucial role in the transition from the fatty streak lesion to the clinically more consequential fibrous plaque and complicated lesion. If further research supports the importance of LDL modification in atherogenesis, a whole new array of possibilities opens itself to us for intervention. Anything that interferes with the relevant modifications of the LDL structure would presumably be additive to interventions lowering the plasma concentration of LDL. At the moment, the only such intervention that appears to be feasible is prevention of LDL oxidation. Possibly we may find ways to interfere with immune mechanisms that are involved in some patients; conceivably we might be able to interfere with the aggregation of LDL with itself or with other complexes in the artery wall that appear also to favor initiation of the atherogenic process. PMID- 2248433 TI - Peroxidized lipoproteins recognized by a new monoclonal antibody (DLR1a/104G) in atherosclerotic lesions. AB - Monoclonal DLR1a/104G antibody, which recognizes peroxidized lipoproteins, was raised. Mice were immunized with the float-up fraction of the atherosclerotic arterial homogenate from WHHL rabbits. Sensitized spleen cells were fused with myeloma cells (3P/U1). Hybridoma clones were selected using peroxidized LDL prepared by CuSO4-catalyzed peroxidation and native LDL as positive and negative standards, respectively. The monoclonal DLR1a/104G antibody was highly reactive with peroxidized LDL, slightly with LDL modified with malondialdehyde, but not significantly with acetyl- or native LDL. The antigenicity in the case of peroxidized LDL did not decrease on extraction with hexane/isopropanol (3:2). The antigenicity coincided with the fluorescence (E350, F430) of the protein fraction of LDL peroxidized with CuSO4. These results suggest that an antigenic determinant exists in atherosclerotic lesions, which is the same as that for lipoproteins peroxidized with CuSO4. PMID- 2248434 TI - Extracellular matrix-smooth muscle phenotype modulation by macrophages. PMID- 2248435 TI - Vascular signal transduction and atherosclerosis. PMID- 2248436 TI - The involvement of lipoproteins in atherogenesis. Evolving concepts. PMID- 2248437 TI - The control of vascular endothelial cell injury. AB - The mechanism by which MCI-186 showed a potent cytoprotective effect on the in vitro endothelial cell injury due to 15-HPETE was studied. Stimulation of human leukocytes with various chemical mediators such as TPA, f-Met-Leu-Phe, LTB4, etc. elicited the production of active oxygens, which could be detected by luminol dependent chemiluminescence. Among the chemical mediators tested, TPA elicited the chemiluminescence the most, and f-Met-Leu-Phe and LTB4 came next. When the leukocytes were directly placed on a monolayer of cultured endothelial cells, followed by stimulating the leukocytes with TPA, severe endothelial cell injury was observed. The effect of TPA was dose dependent. There was good correlation between the active oxygen releasing activity and the cytotoxic activity. When the leukocytes were placed on a filter which was set apart from the monolayer of endothelial cell in a culture dish, and stimulated the leukocytes with TPA, no cytotoxicity was observed. These data strongly suggest that the substance responsible for the cytotoxicity must be a very labile and short-lived substance, presumably active oxygens. On the other hand, MCI-186 was found to have a complete quenching activity to the chemiluminescence due to active oxygens in the TPA-leukocyte system. Taken together, these factors indicate that the potent cytoprotective effect of MCI-186 may be due to its specific radical scavenging activity. PMID- 2248438 TI - The role of atherogenic low density lipoproteins (LDL) in the pathogenesis of atherosclerosis. PMID- 2248439 TI - Autocrine system for smooth muscle cell migration and proliferation in the arterial wall. PMID- 2248440 TI - Pathobiology of vascular cells in vitro in relation to human atherogenesis. Organ and species differences. PMID- 2248441 TI - Multinucleated variant endothelial cell. Its characterization and relation to atherosclerosis. PMID- 2248442 TI - The fibrinolytic system of the vessel wall and its role in the control of thrombosis. PMID- 2248443 TI - Vascular injuries induced by materials released from white mural thrombus and hypercholesterolemia in vivo. AB - Materials released from platelet-rich white mural thrombi into the arterial circulation and dietary hypercholesterolemia could cause endothelial injury and regeneration, and also smooth muscle cell migration and proliferation in vivo in the intima. In addition, a combination of these two factors showed an additive effect on the endothelial injury in vivo. Further experiments are in progress to clarify how high a level of serum cholesterol and/or oxidized LDL may be sufficient for endothelial injury using this in vivo model for the better understanding of detailed pathogenesis of atherosclerosis. PMID- 2248444 TI - The effects of augmented hemodynamic forces on the progression and topography of atherosclerotic plaques. AB - In order to clarify mechanisms determining different degrees of vulnerability of atherogenesis between the apical and the proximal lateral walls at branchings, both regions of the inferior mesenteric artery in human autopsy cases were investigated electron microscopically. The lateral wall and the apex have been accepted by many researchers as the most preferential and the most resistant sites, respectively, for the disease. In regard to blood flow, the apex is exposed to laminar high shear stress, but the outer lateral wall to turbulent low shear stress. In newborns, intimal thickness in the apex was greater than that in the lateral wall, due mainly to the proliferation of SMC. After the 3rd decade, collagen fibers drastically increased in the apical intima, and SMC embedded between the collagen fibers, modulating their phenotypes from synthetic to contractile. In the lateral intima, SMC remained as the synthetic type. Synthetic SMC are considered capable of proliferation in the arterial wall. The lateral intima was generally abundant in proteoglycans and lacked collagen (including subendothelial basement membranes) as well as elastic fibers, particularly in the upper part of the intima. Such a structural difference may cause favorable conditions for atherosclerosis. Results of in vitro studies revealed that collagen gel suppressed proliferation of SMC and changed their phenotype from synthetic to contractile. Therefore, laminar high shear stress gives the arterial wall resistancy to atherogenesis through this phenotypic change. Rabbits showed preferential regions in certain areas of the flow divider for lipid deposition which were different from those of human beings. These regions were covered by ellipsoidal endothelial cells, which should be exposed to relatively low mean shear stress. Ellipsoidal endothelial cells had already been observed in intact rabbits. Therefore, we can conclude that atherogenic processes could be initiated by relatively low mean shear stress in either humans or rabbits. PMID- 2248445 TI - A new approach to prevention and treatment of atherosclerosis by dyslipoproteinemia. PMID- 2248446 TI - Studies on lipid particles in atherosclerotic lesions. PMID- 2248447 TI - Eicosapentaenoic acid and apoplexy. Influence of EPA loading on SHRSP. PMID- 2248448 TI - Antiplatelet therapy for atherosclerotic disorders. AB - Recent studies have revealed the important roles of platelets in atherogenesis via vascular injury. Our in vivo and in vitro studies clearly demonstrate that activated platelets directly inflict injury to vascular endothelial cells, which is associated with a decrease in intracellular cyclic AMP levels in vascular tissues. Antiplatelet therapy is clinically important not only for the prevention of thrombotic episodes but also for the prevention of vascular injury and atherosclerosis. A small dose of aspirin (80 mg) induces clinically hypoaggregativeness of platelets with concomitantly decreased levels of thromboxane A2 in plasma. Our clinical study involving more than 3 years of treatment with small doses of aspirin demonstrated favorable therapeutic effects characterized by hypoaggregation of platelets and increased levels of cAMP and 6 keto PGF1 alpha in plasma which will aid in the prevention of atherosclerosis. PMID- 2248449 TI - Current use of antiplatelet drugs in stroke syndromes in the USA. PMID- 2248450 TI - Atherogenic lipoproteins resulting from genetic defects of apolipoproteins B and E. AB - Accelerated atherosclerosis occurs in patients with type III hyperlipoproteinemia and familial hypercholesterolemia. These genetic disorders focus attention on specific types of lipoproteins as being responsible for the development of accelerated coronary artery heart disease. The accumulation of chylomicron remnants of intestinal origin and of VLDL remnants or IDL of hepatic origin observed in type III hyperlipoproteinemia appears to correlate with coronary disease. The presence of defective forms of apo E prevents normal receptor mediated catabolism of these lipoproteins. Patients with familial hypercholesterolemia have an elevation of plasma LDL (and to a lesser extent an increase in VLDL remnants and IDL) secondary to defective LDL receptors that impair normal catabolism. Familial defective apo B100 is secondary to an abnormality of apo B100 that prevents the normal interaction of LDL with the LDL receptor and increases plasma LDL. However, it has not yet been established that familial defective apo B100 predisposes affected individuals to accelerated atherosclerosis. Animals fed diets high in saturated fat and cholesterol have an accumulation of beta-VLDL, IDL, and LDL that resembles the changes in lipoproteins observed in patients with these genetic disorders. Macrophages (which are presumably derived from circulating monocytes) have emerged as a likely key component in atherogenesis because they appear to be progenitors of foam cells in arterial lesions. Macrophages in the arterial wall express receptors that recognize chylomicron remnants and VLDL remnants (beta-VLDL) and chemically modified LDL. Thus, in the presence of these specific lipoproteins, macrophages are converted to cells that resemble foam cells. The precise stimulus that causes monocyte-derived macrophages to enter specific regions of the arterial wall remains to be determined. PMID- 2248451 TI - Clinical studies on atherosclerosis in diabetics. PMID- 2248452 TI - Mutations in the low density lipoprotein receptor gene in Japanese patients with familial hypercholesterolemia. PMID- 2248453 TI - Lessons in prevention of atherosclerosis learned from recent studies of Japanese youth. AB - 1) The incidence of myocardial infarction, as well as thrombosis, has been increasing recently in the consecutive autopsy cases over 40 years old in Kyushu University, but is still less frequent than those in the autopsy cases in Boston around 1960. Increased fat intake might play a significant role in the increasing frequency of myocardial infarction in Japanese. 2) In a nationwide cooperative study of atherosclerosis in young Japanese, atherosclerotic changes were observed to begin developing in childhood. Primary prevention of atherosclerosis should be initiated in the pediatric age group. We should pay more attention to subclinical atherosclerosis. Age, serum cholesterol, and blood pressure were significantly and positively correlated with SI and AI of aortas and coronary arteries. Serum cholesterol was more strongly correlated with the extent of fatty streaks than was mean blood pressure and vice versa with that of fibrous plaques. Atherosclerosis of cerebral arteries, however, showed a significant correlation only with the factor of mean blood pressure. Therefore the susceptibility to risk factors varies with the artery in the case of early lesions of atherosclerosis in young people. More attention should be paid to the fact that atherosclerosis is a multifactoral disease. 3) Deposition of fibrinogen in the intima might precede LDL deposition and possibly play a more important role than LDL in the development of atherosclerotic lesions in the cerebral arteries, especially in their early stage. 4) The proliferation of smooth muscle cells is stimulated by fibrin and later inhibited by FDP, as produced by fibrinolytic activity of smooth muscle cells. The metabolism of fibrin in the arterial wall may be of importance in the regulation of smooth muscle cell proliferation, and the coagulation fibrinolysis system may play a significant role in atherosclerosis with the effect of other risk factors such as cholesterol and hypertension. PMID- 2248454 TI - Atherosclerosis in Japanese youth with reference to differences between each artery. PMID- 2248455 TI - The contribution of studies of atherosclerotic lesions in young people to future research. PMID- 2248456 TI - Effects of preceding mural thrombus on the pathogenesis of final obstructive coronary thrombosis. AB - Of sixty-four acute myocardial infarcts showing myocardial necrosis within 5 days after onset, 37 had fresh coronary occlusive thrombi with recent thrombus in the deep layer. The recent thrombi were usually located in the severely stenosed segment of arteriosclerotic coronary arteries. They adhered to the intima not only near but on the opposite site to the plaque ulcers and sometimes covered the ulcer. In two thirds of the cases, both the recent thrombi and plaque ulcers were located in the same segment. In the others, the topographical relationship of plaque ulcers to recent thrombi in the longitudinal direction varied from one case to another. These findings show that the recent thrombus might play an important role in the formation of a fresh occlusive thrombus and plaque ulcer of coronary arteriosclerotic lesions. PMID- 2248457 TI - The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence. AB - Based on the findings presented in this study, we propose the hypothesis that calcium could be a mediator for the development of atherosclerosis. Figure 8 shows a schematic illustration of the hypothesis. The presence of risk factors such as hypertension, hyperlipidemia, and smoking may increase the influx of calcium into vascular ECs. We have shown that reactive oxygen species, which are considered to be a risk factor for the development of atherosclerosis, actually increase [Ca++]i in vascular ECs. Increased intracellular calcium may damage the function of ECs, resulting in platelet aggregation at the damaged site. Increased intracellular calcium may also increase uptake of macromolecules in plasma such as fibrinogen and LDL, eventually forming atherosclerotic plaque. We have also shown that the influx of calcium into vascular ECs is associated with LDL transport across vascular ECs. The pretreatment by nifedipine inhibited both the increase in [Ca++]i and the increase in LDL transport, suggesting that intracellular calcium modulates LDL transport across ECs. Growth factors released from platelets may provoke migration and proliferation of medial SMCs in the aterial intima. It has been reported that migration of SMCs from arterial media to intima is enhanced by the presence of calcium, and can be inhibited by the pretreatment of calcium antagonist. As demonstrated in this study, calcium also plays an important role in the proliferation of SMCs provoked by some kinds of growth factors such as EGF. On the other hand, we found that an increased amount of dietary Mg suppressed the development of atherosclerotic lesions in the aorta of cholesterol-fed rabbits without affecting plasma total cholesterol and HDL cholesterol concentrations. The mechanism of action might also be related to the calcium entry blocking action. The clinical and nutritional implications of these phenomena should be investigated further. The evidences presented in this study, however, would not be sufficient to fully explain the etiological role of calcium in atherogenesis. Further studies are required to elucidate the mechanism of the contribution of calcium to atherogenesis. The efficacy of calcium antagonist for the prevention of atherosclerosis in humans should also be investigated further. PMID- 2248458 TI - Clinical and experimental approaches to the prevention of atherosclerosis by immunological regulations. AB - To evaluate the involvement of the complement system in atherogenesis, we investigated the effect of camostat mesilate (CM), C1r, and C1 esterase inhibitor on cholesterol-induced atherosclerosis in rabbits. We also examined the effect of sodium dextran sulfate (DS, molecular weight: 7000), which is reported to be effective in preventing arteriosclerotic diseases and in inhibiting cholesterol induced atherosclerosis in experimental animals, on complement activation in vitro and in vivo. The administration of CM reduced the formation of atherosclerotic lesions in cholesterol-fed rabbits. DS inhibited complement pathway in vitro, and the administration of DS reduced the C3a level in subjects. These results suggest that complement activation may possibly be involved in the atherosclerotic process. PMID- 2248459 TI - Possible role of dietary proteins and amino acids in atherosclerosis. PMID- 2248460 TI - The effect of milk intake on serum cholesterol in healthy young females. Randomized controlled studies. PMID- 2248461 TI - Disproportionally high concentrations of apolipoprotein E in the interstitial fluid of normal pulmonary artery in man. PMID- 2248462 TI - Risk factors for atherosclerotic vascular diseases with special reference to the relationship between apolipoprotein E mutations and hyperlipidemia. PMID- 2248463 TI - Collagen metabolism in atherogenesis. PMID- 2248464 TI - Increased triglyceride may determine the sites of coronary arterial lesions. PMID- 2248465 TI - Experimental production of intramural hemorrhage by induced coronary artery spasm in atherosclerotic miniature swine. Experimental proof on the roles of spasm in cardiac events of ischemic heart disease. PMID- 2248466 TI - Adrenaline and noradrenaline as possible chemical mediators in the pathogenesis of arteriosclerosis. AB - We studied the relationships between adrenaline and noradrenaline and factors associated with arteriosclerosis to determine whether catecholamines contribute to the atherogenetic process. We investigated the effects of adrenaline and noradrenaline on cultures of vessel wall cells from rats and analyzed plasma catecholamine levels in humans exposed to atherogenic risk factors, undergoing hemodialysis treatment or following myocardial infarction or stroke. I. Cultured endothelial and smooth muscle cells from vessel walls exhibited enhanced proliferation when exposed to adrenaline or noradrenaline. This indicates that catecholamines trigger the activation of vascular wall cells in vitro. Such activation, the unspecific mesenchymal reaction, is the predominant characteristic change in early atherogenesis. II. In individuals subjected to the atherogenic risk factors smoking, essential hypertension and mental stress, plasma adrenaline concentrations were statistically significantly elevated. Mental stress also caused significantly elevated plasma noradrenaline levels. Plasma noradrenaline concentrations were also elevated in smoking and hypertensive individuals when compared with certain controls, but the differences failed to be statistically significant. III. In dialysis patients, plasma adrenaline and noradrenaline concentrations showed a positive correlation with the activity of the sclerotic process; i.e., plasma catecholamine concentrations increased with the severity of the disease. IV. Patients with persisting arteriosclerotic vascular disease, i.e., patients who had had a myocardial infarction or stroke, had significantly elevated plasma adrenaline and/or noradrenaline levels as late as one year after the event. The results of our investigations suggest that adrenaline and noradrenaline may act as chemical mediators during atherogenesis in man, thus contributing to the development and subsequent complications of arteriosclerosis. PMID- 2248467 TI - The key scientific issue of the next century: the science of addiction. AB - The problem of addiction is believed to be the most important scientific issue of the next century. The solution to the riddle of pharmacologic, psychological, and social addiction to nicotine, heroin, alcohol, and a high-fat diet, and the discovery and implementation of strategies for spreading healthy "addictions" will aid in solving many major public health and social science problems in the next century. All-out efforts should be expended on the comprehensive development of a science of addiction and to the wide-scale effective application of the results of such research in order to promote health, prosperity, and peace for every community in the world. PMID- 2248468 TI - Occupational health research in the process of industrialization in China. PMID- 2248469 TI - The role of the Medical Academy. PMID- 2248470 TI - Biomedical science: some controversial issues. PMID- 2248471 TI - Recent trends in cancer. PMID- 2248472 TI - AIDS and the future of science. PMID- 2248473 TI - Low fertility in industrial countries: causes, consequences, policies. PMID- 2248474 TI - Individual programming of life events: a challenge for demographers in the twenty first century. PMID- 2248475 TI - In vitro effects of neuropeptide Y at the vascular neuroeffector junction. PMID- 2248476 TI - Neuropeptide Y-cholinergic interactions in neocortical tissue. PMID- 2248477 TI - Neuropeptide Y and memory processing. PMID- 2248478 TI - Neuropeptide Y in the circadian timing system. PMID- 2248479 TI - Role of neuropeptide Y in reproductive function. AB - NPY acts both at the hypothalamus and the anterior pituitary gland to modulate reproductive hormone secretion. Within the hypothalamus, NPY stimulates LHRH secretion in the presence of physiological levels of estrogen and suppresses pulsatile LHRH release following ovariectomy. Intracerebroventricular injection of NPY antiserum blocks or delays the LH surge in steroid-primed ovariectomized rats, thereby adding support for a physiological role of NPY in the neuroendocrine events preceding ovulation. Blockade of alpha 2 adrenergic receptors decreases NPY-stimulated LH release in steroid-primed rats implying a potential noradrenergic mediation of NPY activity. Physiological levels of progesterone do not augment, and may actually suppress NPY-induced LHRH secretion in vitro from median eminences obtained from estrogen-primed ovariectomized rats. The physiological role of progesterone, if any, in modulating NPY effects on LHRH release remains to be determined. Little, if anything, is known about the NPY receptor in the median eminence or the intracellular mechanisms which transduce the NPY signal into activation of LHRH release in estrogen-treated ovariectomized rats although translocation of intracellular calcium is required. Equally puzzling is the mechanism of desensitization of the LHRH-releasing mechanisms of the median eminence of ovariectomized rats or the specific site of NPY suppression of pulsatile LHRH secretion. NPY is released into the hypothalamo hypophysial portal circulation and this appears correlated with LHRH secretion before the LH surge. NPY affects LH and FSH release from anterior pituitary cells in vitro and enhances LHRH-induced LH secretion. Taken together, the studies described above suggest an important physiological role for NPY as a modulator of neuroendocrine activity which culminates in the preovulatory surge of LH. PMID- 2248480 TI - Biologically active neuropeptide Y analogs. PMID- 2248481 TI - Hypothalamic neuropeptide Y: a circuit in the regulation of gonadotropin secretion and feeding behavior. PMID- 2248482 TI - Hypothalamic neuropeptide Y in relation to energy balance. PMID- 2248483 TI - Regulation of MSH secretion by neuropeptide Y in amphibians. PMID- 2248484 TI - Neuropeptide Y and the anterior pituitary. PMID- 2248485 TI - Pancreatic polypeptide and peptide YY gene expression. PMID- 2248486 TI - Molecular structure of neuropeptide Y. AB - The original description of NPY following its isolation commented on its homology to the pancreatic polypeptide family of peptides. This homology is extended to the mRNA sequences and the genomic structure, suggesting that this family has arisen as a result of gene duplication. However, each member demonstrates remarkable specificity in its expression within tissue types. The expression of the NPY gene is thus controlled by, as yet undefined, factors regulating to neural cells. The level of expression within cells is dependent on nerve growth factor. However, other factors, such as the rate of processing of the precursor, may be involved in regulation of the stored concentrations of the peptide product. PMID- 2248487 TI - Regulation of the human neuropeptide Y gene. PMID- 2248488 TI - Extraorbital use of a disinserted superior oblique as a sling in third nerve palsy: a new single-stage surgical technique. AB - The management of third cranial nerve palsy is surgical. The usual technique is to correct alignment of the eyes in the first stage, followed by ptosis correction by a sling operation in the second stage. A new single-stage surgical technique involved the disinsertion of superior oblique muscle to bring the eye in a midline position. Simultaneously it is used extraorbitally as a sling to raise the ptotic upper eyelid. Postoperatively a fairly good cosmetic effect was achieved, but the upper eyelid showed a paradoxic aberrant elevation on eso depression. PMID- 2248489 TI - Anterior segment ischemia: a complication of retinal detachment repair in a patient with sickle cell trait. AB - Anterior segment ischemia (ASI) is a dreaded complication of retinal detachment surgery particularly in patients with predisposing factors such as sickle cell disease. We report a case of ASI after scleral buckling in an otherwise healthy black patient with sickle cell trait. Conditions of relative hypoxia intraoperatively from either anesthesia or surgical manipulation may precipitate vasoocclusive phenomena in these normally asymptomatic patients. Since the incidence of sickle cell trait in the black population in the United States is 8.5%, we recommend these patients have a preoperative sickle test followed by hemoglobin electrophoresis with quantification if positive. The presence of sickle cell trait should alert the surgeon to the risk of ASI, and factors predisposing to hypoxia should be minimized when possible. PMID- 2248490 TI - Selective photoreceptor cell loss in hypoxic ischemia. AB - We studied the histopathologic changes in the brain and eye of a 5 1/2-month-old infant who suffered a profound hypotensive episode three days antemortem. Nuclear pyknosis and other histologic changes characteristic of ischemic cell necrosis were found throughout the brain and in the retina's photoreceptor-cell layer. These findings suggest that hypoxic ischemia may produce preferential damage to the photoreceptor-cell layer. PMID- 2248491 TI - Sudden blindness after thermocoagulation of the trigeminal ganglion. AB - Sudden blindness during percutaneous thermocoagulation of the gasserian ganglion occurred in a 72-year-old woman with trigeminal neuralgia. Considered a safe procedure, we highlight the possibility of this serious complication which was probably due to direct damage of the optic nerve. PMID- 2248492 TI - Monoscleral fixation for posterior chamber intraocular lenses in cases of posterior capsule rupture. AB - A method for monoscleral fixation of posterior chamber intraocular lenses in posterior capsule rupture is described. Five lenses fixated with this technique are reviewed. PMID- 2248493 TI - Central retinal artery obstruction in herpes zoster ophthalmicus and cerebral vasculopathy. AB - We present a case of acute central retinal artery obstruction in association with Herpes zoster ophthalmicus and delayed cerebral vasculopathy. Retinal vascular obstruction is rare in zoster, and its occurrence during postherpetic cerebral vasculopathy has not been reported previously to our knowledge. The syndrome of delayed cerebral vasculopathy is discussed as is its possible relationship to central retinal artery obstruction. PMID- 2248494 TI - Nylon suture toxicity after vitrectomy surgery. AB - A patient underwent an uneventful pars plana vitrectomy with superior sclerotomies closed with 8-0 nylon suture. Four months later, the patient had a suture reaction presumably related to allergy to the suture itself. The signs and symptoms resolved after removal of the suture. Although similar cases have been reported after nylon sutures in cataract wound closure, this is the first reported occurrence of this phenomenon in vitrectomy surgery to our knowledge. PMID- 2248495 TI - Contact transscleral laser cyclocoagulation in glaucoma. AB - A new way to treat glaucoma by laser coagulation of the ciliary body was developed. The laser beam is channeled to the eye through the fiberoptic system. The tip of the fiberoptic probe is placed in direct contact with the surface of the eye to be treated. The technical equipment developed for contact transscleral laser cyclocoagulation is simple, practical, and easy to use. The method was investigated experimentally (on animals and on human eyes to be enucleated) and tried in clinical practice. Only patients facing glaucoma surgery (on whom all other methods of conservative therapy failed) were selected for this kind of treatment. The immediate hypotensive effect was approximately 13 mmHg during the first 24 hours; then there was a gradual elevation of the tension, reducing the initial effect on average by 30%. This method has definite advantages over surgical cyclocoagulation as far as safety and simplicity are concerned. The use of contact fiberoptic systems may open up new possibilities in other fields of laser treatment of glaucoma, including techniques to channel the laser beam to the structures of the anterior chamber angle. PMID- 2248496 TI - James Spence Medallist 1990. Professor Leonard B. Strang. PMID- 2248497 TI - Diagnosis and management of subglottic stenosis after neonatal ventilation. PMID- 2248498 TI - Aplastic anaemia: continued cause for concern. PMID- 2248499 TI - Audit--where do we go from here? PMID- 2248500 TI - Final height in boys with untreated constitutional delay in growth and puberty. AB - To determine the natural history and psychological impact of the growth pattern in boys with constitutional delay in growth and puberty (CDGP), 43 boys presenting with short stature due to CDGP were followed up to final height. At presentation mean (SD) chronological age was 14.0 (1.9) years, bone age delay 2.7 (1.0) years, standing height standard deviation score (SDS) -3.4 (0.6), and predicted adult height SDS -1.3 (0.7). Final adult height SDS was -1.6 (0.9), measured at 21.2 (2.6) years. There was no significant difference between final height and predicted adult height, but there was a significant difference between final height and measured mid-parental height. Psychological questionnaires showed no significant difference in self esteem, marital, or employment state between the CDGP group and a control group. There was no correlation between self esteem and final height, but 25 felt their growth delay had affected their success either at school, work, or socially and 20 would rather have had treatment to advance their growth spurt. This study supports the more frequent use of active medical treatment to advance growth in boys with CDGP, and shows that although boys with CDGP reach their predicted heights, this is short for their families. PMID- 2248501 TI - Hyperinsulinaemic hypoglycaemia in small for dates babies. AB - Blood glucose concentrations were measured prospectively in 27 small for dates infants in the first 48 hours after birth: 10 infants became hypoglycaemic. Of these, five had inappropriately raised plasma insulin concentrations. Plasma free fatty acids were lower and carbohydrate intake higher in these five infants, further supporting the diagnosis of hyperinsulinism. The hypoglycaemia recurred in four of the five hyperinsulinaemic infants, but in none of those who were not hyperinsulinaemic. Hyperinsulinism is common in small for dates babies. It is important to recognise this because hypoglycaemia is likely to recur and appropriate treatment is needed to prevent long term sequelae. PMID- 2248502 TI - Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. AB - Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started. PMID- 2248503 TI - X linked hypophosphataemia: treatment, height gain, and nephrocalcinosis. AB - The clinical data of 18 patients with X linked hypophosphataemia were analysed retrospectively. The height data were expressed as SD scores. There was no difference in the final height of patients treated with vitamin D (or 1,25 dihydroxyvitamin D) and phosphate for at least two years (n = 12) and that of 16 hypophosphataemic family members who had never been treated. The mean final SD score (-2.07) of treated patients, however, was significantly higher than the value before treatment (-2.79), which indicated an average absolute height gain of 4-4.5 cm compared with the expected height values. Six of the treated patients developed ultrasonographically detectable nephrocalcinosis with normal renal function. The daily phosphate intake and excretion of patients with nephrocalcinosis was significantly higher than that of patients with normal renal morphology. There was no difference in the doses of vitamin D between the two groups. The average urinary calcium:creatinine ratio of the two groups was similar to and below the hypercalciuric 0.6 mmol:mmol limit. The group with nephrocalcinosis, however, had a higher incidence of hypercalciuric episodes than the group without nephrocalcinosis (12 in 130 observations compared with six in 334 observations, respectively). The benefits and risks of treatment of patients with X linked hypophosphataemia must be further evaluated. The high dose of phosphate seems to be an important factor in the development of nephrocalcinosis in this group of patients. PMID- 2248504 TI - Reappraisal of thyroxine treatment in primary hypothyroidism. AB - The optimum daily dose of thyroxine was calculated for 13 children aged 3-16 years with primary hypothyroidism by titrating their doses at monthly intervals. The condition of the thyroid was assessed by sensitive assay of thyroid stimulating hormone concentrations, as well as measurement of total and free thyroid hormone concentrations and systolic time interval ratios. Serum thyroid stimulating hormone concentration was found to be the most responsive to small changes in thyroxine. The calculated optimum daily replacement dose of thyroxine (102 micrograms/m2 or 3.5 micrograms/kg) was fractionally lower than that previously recommended, and was more closely related to surface area (coefficient of variation 8.2%) than to body weight (coefficient of variation 16.2%). Our results suggest that though monthly may be the optimal time interval for increases in the dose of thyroxine, any reduction in the dose should be made more gradually. PMID- 2248505 TI - Survey of adolescents with severe intellectual handicap. AB - A diagnostic survey was undertaken of children aged 11 to 19 years in Tameside with severe learning difficulties (intelligence quotient less than or equal to 50). Eighty-two children were identified and their medical records reviewed. A specific diagnosis for the retardation was documented in 25 (30%) of the children, 18 of whom had Down's syndrome. A probable aetiology or a disorder of unknown aetiology had been identified in a further 21 (26%) children. To confirm the existing diagnosis, identify new diagnoses, and offer genetic counselling, the parents of 63 children were offered detailed reassessment of their child. Fifty three children were reviewed, and a specific disorder identified in 25 out of 31 previously undiagnosed children. The most frequent diagnoses made were fragile X syndrome and Rett's syndrome. On completion of the survey, 61 of the 82 children (74%) had a specific diagnosis or probable aetiology identified, 12 (15%) had associated disorders such as cerebral palsy, and in only nine of the 82 children (11%) were there no clues at all to the cause of their retardation. PMID- 2248506 TI - Normal small bowel biopsy followed by coeliac disease. AB - We report four patients (two children, one adolescent, and one adult) having normal small bowel mucosa shown on a biopsy specimen taken before the initial diagnosis of coeliac disease was made. The first biopsy was undertaken in two cases because of suspected malabsorption, in the third because of suspected dermatitis herpetiformis, and in the fourth as part of a coeliac disease family study. After a further 2.6 to 9 years on a diet containing gluten, small bowel villous atrophy with crypt hyperplasia compatible with coeliac disease was found on a second biopsy specimen. The HLA type of the patients was that typical for coeliac disease; all were DR3 positive. Within the families three other patients with coeliac disease have been diagnosed, two earlier and one at the time the first biopsy was undertaken. Four other HLA-DR3 positive haploidentical first degree relatives were found and had biopsies. All four had normal small bowel villous architecture, one had an increased intraepithelial cell count, and another was positive for reticulin and endomysium antibodies. Coeliac disease may exist latent in patients having normal mucosa when eating a normal diet containing gluten. PMID- 2248507 TI - Kawasaki disease: echocardiographic features in 91 cases presenting in the United Kingdom. AB - Ninety-one patients with Kawasaki disease were examined by cross sectional echocardiography between 1980 and 1988. In the 75 patients evaluated during the acute phase of the illness (the first month), the first echocardiographic examination was carried out at a mean time of 16 days (range 5-30) and coronary arterial lesions were seen in 21 (28%). Two patients with medium sized aneurysms had myocardial infarctions, and one died. Coronary arterial lesions persisted in 17 (23%) patients, most often in younger children. The remaining 16 patients were examined from one month to four years after their acute illnesses, and this group did not have coronary arterial abnormalities. Seven patients with coronary artery lesions have reached school age and require regular echocardiographic examination and exercise electrocardiography. Selective coronary arteriography may be indicated in some patients to identify coronary artery stenosis, which the Japanese experience has shown may progress for several years after the acute illness. PMID- 2248508 TI - Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. AB - Seventy-three children with steroid dependent minimal change nephrotic syndrome were randomly allocated to receive treatment with cyclophosphamide (2 mg/kg/day) for either eight or 12 weeks, in combination with prednisolone. All patients had previously relapsed while the dosage was being reduced or within 14 days of discontinuing prednisolone in the six months before receiving cyclophosphamide treatment (steroid dependent), and had severe steroid toxicity. Thirty two patients were treated with cyclophosphamide for eight weeks, and 41 for 12 weeks. There were no differences between the two groups in age at onset of nephrosis or entry into the study, sex ratio, duration of nephrosis, number of relapses before entry, and follow up period after entry. The relapse free rate of patients treated for eight weeks (25%) was similar to that of those treated for 12 weeks (24%) five years after stopping the treatment, and the mean relapse free interval and the sparing effect of cyclophosphamide (if any) on subsequent treatment with steroids did not differ between the groups. We conclude that cyclophosphamide should be used for no longer than eight weeks at a dose of 2 mg/kg/day in children with steroid dependent minimal change nephrotic syndrome. PMID- 2248509 TI - Continuous papaveretum infusion for the control of pain in painful sickling crisis. AB - We describe our experience of using continuous papaveretum infusions to control pain in 24 children admitted on 45 occasions with painful sickling crisis. The children were aged from 1.7 to 14.3 years. Infusion duration ranged from one to nine days (median three days), total dose from 0.3 to 21 mg/kg (median 2.4 mg/kg), with a pronounced tendency for dosage to increase with increasing age. No respiratory depression was observed. One infusion was discontinued because of cerebral toxicity. PMID- 2248510 TI - Predicting treatment outcome in nocturnal enuresis. AB - A presenting sample of 127 consecutive referrals to a community based enuresis clinic were evaluated after treatment with baseline behavioural recording and the enuresis alarm. Almost one in five became dry after baseline recording only while 81 of 96 (84%) enuretics who used the alarm achieved the initial dryness criterion. Successful outcome was associated with the absence of adverse environmental factors and psychiatric disorders in the child. A logistic regression procedure enabled a risk score to be created so that successful outcome could be predicted. Psychiatric disorder in the child, family stress, and the degree of concern shown by the child emerged as the most important prognostic factors in the treatment of enuresis. The favourable success rates with baseline recording and the enuresis alarm confirm the role of conditioning treatment at the forefront of management of enuresis and the risk score allows outcome to be predicted for the first time. PMID- 2248511 TI - Capillary haemangioma presenting as a lung pseudocyst. AB - A girl who developed a lung cyst at 24 hours of age during gentle ventilation for respiratory distress syndrome is reported. Instead of resolving as expected of a pseudocyst it continued to expand. Resection at 1 year of age showed a cyst entirely surrounded by capillary haemangioma. Aspiration of this cyst would have been dangerous. PMID- 2248512 TI - Benign intracranial hypertension after ciprofloxacin administration. AB - Many drugs, including antibiotics, have been implicated in the aetiology of benign intracranial hypertension. We report the development of benign intracranial hypertension after the use of ciprofloxacin in a teenager with cystic fibrosis. PMID- 2248513 TI - 5 alpha-reductase deficiency without hypospadias. AB - A boy aged 4 with penoscrotal hypospadias and his brother aged 12 with micropenis had typical changes of homozygous 5 alpha-reductase deficiency. After three injections of chorionic gonadotrophin there was a trivial rise in plasma dihydrotestosterone with a normal increase in plasma testosterone. Urine steroid chromatography showed abnormally high 5 beta: 5 alpha ratios and 5 alpha reductase activity was appreciably reduced in genital skin fibroblasts. The results indicate that 5 alpha-reductase deficiency is not invariably associated with genital ambiguity. PMID- 2248514 TI - Indomethacin responsive hypercalcaemia associated with a renal sarcoma. AB - An infant presented with a non-metastatic renal spindle cell sarcoma and hypercalcaemia, which resolved after treatment with indomethacin. There was in vivo and in vitro evidence that hypercalcaemia was mediated by circulatory prostaglandins. PMID- 2248515 TI - Management of migraine. PMID- 2248516 TI - Selective medical examinations for school entrants: the way forward. PMID- 2248517 TI - Early identification of hearing loss: screening and surveillance methods. PMID- 2248518 TI - Growth hormone deficiency in children with chromosomal abnormalities. PMID- 2248519 TI - Lichen sclerosis. PMID- 2248520 TI - Surveillance for anaemia: risk factors in pattern of milk intake. PMID- 2248521 TI - Collecting 24 hour urine samples from children. PMID- 2248522 TI - Glucose polymer regimens and hypernatraemia. PMID- 2248523 TI - Ozone in medical gases. PMID- 2248524 TI - Hearing screening in children--state of the art(s) PMID- 2248525 TI - The genetics of deafness. PMID- 2248526 TI - Postviral fatigue syndrome. PMID- 2248527 TI - Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance. AB - Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmann's syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms. PMID- 2248528 TI - Increase in urinary growth hormone excretion in puberty. AB - During the pubertal years the overnight urinary excretion rate of growth hormone (hGHu) increases to three to four times the prepubertal rate, reaching a peak in girls at 13 years and in boys at 15 years. After puberty the mean rate of overnight hGHu is twice that before puberty. PMID- 2248529 TI - Assessment of gonadal maturation by evaluation of spermaturia. AB - The urinary excretion of spermatozoa (spermaturia) reflects the achievement of exocrine testis function during male puberty. In order to test the sensitivity and practicability of repetitive urine sampling, we analysed the sediments of 1160 first morning urine specimens obtained on successive days from 129 healthy schoolboys aged 10.1 to 17.8 years for the presence of spermatozoa. The proportion of subjects with sperm positive urines increased from pubic hair stage (PH) 1 (6%) to PH 5 (92%) with a steep rise between PH 2 and 3. Estimated median age of first positive spermaturia ('spermarche') was 14.1 years. While at PH 1 to 4 all positive samples were found within the first five days of collection, at PH 5 cumulative frequency of spermaturia increased up to day 8. We conclude that repetitive morning urine sampling is a useful tool in assessing spermaturia and may be helpful to screen for testicular damage in epidemiological surveys. PMID- 2248530 TI - Indices of intact serum parathyroid hormone and renal excretion of calcium, phosphate, and magnesium. AB - Up to date reference ranges were established for fasting renal excretion of calcium, phosphorus, and magnesium on 101 healthy children aged 2-15 years. A normal range for intact parathyroid hormone was also measured. The indices of calcium and magnesium excretion showed no correlation with age or sex so that a common range for all children could be established. The 97th centile values for urinary calcium:creatinine and magnesium:creatinine ratios were 0.69 mmol:mmol and 1.05 mmol:mmol respectively. The calculated tubular maximum for phosphate/litre of glomerular filtrate (TmPO4/GFR) showed no correlation with age with a geometric mean value of 1.67 mmol/l. The normal range for intact serum parathyroid hormone for the age group was 11-35 ng/l, which is lower than the adult normal range using the same assay. There was an inverse correlation between TmPO4/GFR and intact parathyroid hormone in this group of normal children. PMID- 2248531 TI - Helicobacter pylori and associated duodenal ulcer. AB - Twenty three children with coexistent duodenal ulcer and Helicobacter pylori infection were treated with either two weeks of amoxycillin (25 mg/kg/day) in addition to six weeks of cimetidine, or cimetidine alone. Endoscopy with antral and duodenal biopsies for urease test, microaerophilic culture, and histological studies were performed at entry, six weeks, 12 weeks, and at six months. Children with persistent H pylori infection at six weeks were given a further two weeks' course of amoxycillin. H pylori persisted in all children not receiving amoxycillin treatment but cleared in six of the 13 children (46%) treated with amoxycillin. With failure of H pylori clearance at six months, only two out of six (33%) ulcers had healed and 50% of patients had experienced ulcer recurrence. In contrast, when H pylori remained cleared all ulcers healed and no ulcer recurred. Persistent H pylori infection was associated with persistent gastritis and duodenitis despite endoscopic evidence of ulcer healing. Detection and eradication of H pylori deserves particular attention in the routine management of duodenal ulceration in children. PMID- 2248532 TI - Severe hypertension after liver transplantation in alpha 1 antitrypsin deficiency. AB - Five children with alpha 1 antitrypsin deficiency and terminal liver disease received liver grafts; all five became hypertensive and four developed hypertensive encephalopathy. There was evidence of renal disease preoperatively and renal biopsy specimens showed variable glomerulonephritic histology with IgA nephropathy in one, mesangial-proliferative changes in two, and mesangio capillary glomerulonephritis type I in two. Four hypertensive episodes were preceded by a fall in creatinine clearance. The association of glomerulonephritis with alpha 1 antitrypsin deficiency in children is more common than has been recognised. Affected patients are prone to severe hypertension of probable renal origin after liver transplantation and the renal lesion may affect long term prognosis. PMID- 2248533 TI - Corticosteroids in primary tuberculosis with bronchial obstruction. AB - The usefulness of prednisolone in combination with the modern potent antituberculous drugs has been studied in 29 children with primary lung tuberculosis and hilar adenopathy causing bronchial obstruction. These children were divided at random in two groups of 15 and 14 patients. Both groups were treated similarly except that one group received prednisolone. Both groups were very similar before the onset of treatment for most variables. Tuberculous infection healed in both groups but the group on steroids improved earlier and had significantly fewer complications, both on radiography and bronchoscopy. Only two of the patients on steroids still had progressive lesions: a very young baby probably because he developed two severe viral infections consecutively, and another infant of 7 months whose treatment was unreliable, as the parents were not very compliant. Some patients initially not treated with prednisolone improved only after it was given. Prednisolone treatment is not recommended when the reliability of the treatment cannot be guaranteed, as the hazard of harm would exceed the expected benefit. PMID- 2248534 TI - Perianal appearances associated with constipation. AB - The perianal appearances were studied prospectively of 136 constipated children (mean age 3.9 years, 67 boys, 69 girls). Anal dilatation, fissures, tags, warts, perianal oedema, redness, blueness, and veins were recorded. It was noted whether dilatation occurred immediately or at 30 and 60 seconds with the buttocks minimally separated, and on subsequent firm lateral traction of the buttocks. The degree of faecal loading was assessed in all children. Anal dilatation was found in 24 (18%) and first appeared on lateral traction in eight (6%). In three quarters of the children with dilatation faecal loading or perianal signs were present. Fissures were found in 35 (26%) children and tags in seven (5%). Perianal redness was more likely to be associated with fissures, and blueness with dilatation. We conclude that there are no pathognomonic perianal signs in childhood constipation and that the technique of anal examination should be standardised. PMID- 2248535 TI - Ventilator dependency in the United Kingdom. AB - There are 24 children who are currently long term ventilator dependent in the UK. Nine of these are cared for entirely at home. An additional 11 children have been long term ventilator dependent since March 1983. The prevalence of these children appears to be increasing. The financial and manpower resources needed for these children whether at home or in hospital is considerable. There are reasons to suppose that the apparent increase in prevalence will continue. PMID- 2248536 TI - Effects of newborn screening of cystic fibrosis on reported maternal behaviour. AB - Screening for cystic fibrosis is highly controversial. Concerns have been expressed that newborn screening may cause mothers, who had considered their child to be healthy before diagnosis, to overprotect their child. Some critics of screening also suggest that a period of delay from onset of symptoms to diagnosis may help a mother adjust to the reality of the child's lethal condition. This study compared the strength of overprotective child rearing attitudes of 29 mothers whose children were screened (13 had symptomatic children and 16 asymptomatic children) with the attitudes of 29 mothers whose children were diagnosed after the onset of symptoms. Results indicate that newborn screening had not increased a mother's tendency to overprotect her child with cystic fibrosis and in some cases the tendency had decreased. Further, delay in diagnosis when screening was not conducted usually caused mothers considerable personal distress. PMID- 2248537 TI - Central nervous system vasculitis after chickenpox--cause or coincidence? AB - A 7.5 year old boy, known to have a seizure disorder, presented with an infarct in the left middle cerebral artery territory, 10 weeks after severe chickenpox. Immunofluorescent antibody titre to the varicella zoster virus in the cerebrospinal fluid was 1:32. Cerebral angiography showed evidence of focal vasculitis. He presented again seven months later with an acute exacerbation of seizures. Magnetic resonance imaging of the brain showed an old posterior extension of the infarct, but a repeated angiography demonstrated an improvement in the vasculitic process. Cerebrospinal fluid antibody titre was again 1:32. Although this may have been an unfortunate coincidence, a possible association between chickenpox and vasculitis, similar to that reported with herpes zoster, and with potentially significant clinical implications, should be considered. As a definite proof can be obtained only by a brain biopsy, however, which is generally not indicated in such cases, only additional clinical reports can lead to delineation of this association as a definite entity. PMID- 2248538 TI - Reproducibility of 24 hour oesophageal pH studies in infants. AB - Thirteen infants who had undergone 24 hour oesophageal pH monitoring to diagnose gastro-oesophageal reflux had a second study carried out to see if the results were reproducible. The studies were done without restricting the babies' activities. Appreciable differences were found, the percentage of the total time during which the pH was less than 4 varying by up to 3.7-fold between the two tests. The differences were largely the result of biological rather than technical variability. From these results estimates were made of the reliability of a single diagnostic study and the size of changes that would be necessary to show the effect of treatment. These findings have a considerable impact on the diagnosis of abnormal gastro-oesophageal reflux and its response to treatment whether using 24 hour pH monitoring or any other method of measurement. PMID- 2248539 TI - Bronchial asthma and acid reflux into the distal and proximal oesophagus. AB - The prevalence of pathological gastro-oesophageal reflux in children and adolescents with asthma was studied by 24 hour two level oesophageal pH monitoring in 42 subjects aged 9-20 years with moderate or severe bronchial asthma. The importance of oesophagobronchial nerve reflexes and of aspiration of gastric acid as triggers in asthma was assessed by studying whether episodes of reflux into the distal and into the proximal oesophagus were followed by asthma attacks. Twenty-one subjects (50%) had a pathological total reflux time in the distal oesophagus and six (16%) in the proximal oesophagus. Nine patients had pathological gastro-oesophageal reflux into the distal oesophagus together with symptoms of asthma during the day on which the recording took place. In three of them the episodes of asthma symptoms were significantly correlated with preceding episodes of reflux into the distal oesophagus, and in one subject to reflux into the proximal oesophagus. We conclude that pathological gastro-oesophageal reflux is common in children and adolescents with asthma, but it seems to provoke symptoms of asthma in only a few. Symptoms of asthma were more often elicited by exposure of the distal oesophagus to gastric acid, possibly by a vagal reflex, than by aspiration of gastric juice. PMID- 2248540 TI - Air leaks and vasopressin release. AB - Eleven very low birthweight babies being ventilated for respiratory problems during the first week of life developed air leaks on 22 occasions. On 16 out of 19 occasions the infants showed increases in urinary excretion of vasopressin after these events and on 10 occasions out of 13 there was a rise in the plasma arginine vasopressin concentration. The peripheral signs of the syndrome of inappropriate antidiuretic hormone release were seen on only one occasion in response to the sometimes high vasopressin concentrations. PMID- 2248541 TI - Use of thermographic imaging to study babies sleeping at home. AB - Two 3 month old infants sleeping under different thermal conditions were found to maintain similar deep body temperatures. Thermographic imaging suggested that though the uncovered head is the main source of heat transfer, other parts of the body such as the hands may be used when necessary. PMID- 2248542 TI - Continued need for pneumococcal prophylaxis after splenectomy. AB - Two children died from pneumococcal infection five and eight years after splenectomy. Pneumococcal vaccination had not been given to either child. When the infection developed both children were not taking prophylactic penicillin. Vaccination and daily penicillin reduce the incidence of this complication and therefore we strongly recommend that both of these measures are continued indefinitely. PMID- 2248543 TI - Visceral leishmaniasis in a Scottish child. AB - A Scottish girl acquired visceral leishmaniasis (kala-azar) while on holiday in Majorca. She presented with the infection, six months later, in Scotland. Because of inexperience with the disease and a degree of scepticism unnecessary investigations were carried out resulting in a delay in treatment. PMID- 2248544 TI - Crohn's disease of the lung. AB - Two years after developing colonic Crohn's disease, a 17 year old boy presented with focal pulmonary consolidation. A lung biopsy specimen showed areas of non caseating epithelioid granuloma. Although some respiratory abnormalities appear to be associated with inflammatory bowel disease, granulomatous disease affecting the lung has not previously been reported in a child. PMID- 2248545 TI - Topical anaesthesia for repair of minor lacerations. AB - One hundred traumatic skin wounds were sutured under topical anaesthesia using a solution of lignocaine, adrenaline, and cocaine, and the effectiveness of the anaesthesia produced was assessed on a behavioural scale. The procedure was tolerated well by 63 patients, poorly by 11, and in 26 the response was uncertain. The response correlated well with age and with the field of anaesthesia measured from the wound margin. No toxic reactions were observed. PMID- 2248546 TI - Helicobacter pylori. PMID- 2248547 TI - The cytokines are coming. PMID- 2248548 TI - Head injury--how community paediatricians can help. PMID- 2248549 TI - Genetic engineering of plants for virus resistance. AB - Historically, control of plant virus disease has involved numerous strategies which have often been combined to provide effective durable resistance in the field. In recent years, the dramatic advances obtained in plant molecular virology have enhanced our understanding of viral genome organizations and gene functions. Moreover, genetic engineering of plants for virus resistance has recently provided promising additional strategies for control of virus disease. At present, the most promising of these has been the expression of coat-protein coding sequences in plants transformed with a coat protein gene. Other potential methods include the expression of anti-sense viral transcripts in transgenic plants, the application of artificial anti-sense mediated gene regulation to viral systems, and the expression of viral satellite RNAs, RNAs with endoribonuclease activity, antiviral antibody genes, or human interferon genes in plants. PMID- 2248550 TI - Infected cell specific protein and viral DNA synthesis in productive and abortive infections of Spodoptera frugiperda nuclear polyhedrosis virus. AB - This study examines viral protein and DNA synthesis in Spodoptera frugiperda multicapsid nuclear polyhedrosis virus (SfMNPV) infections of S. frugiperda and Trichoplusia ni cells. A total of 28 infected cell specific polypeptides (ICSPs) were detected in the productive S. frugiperda cells. Of these, 14 were identified as structural polypeptides. Based on the change in their rate of synthesis during the replication cycle, these ICSPs were grouped into four classes. Only a 97k and a 29k ICSP were detected in SfMNPV infections of T. ni cells. Inhibition of host protein synthesis occurred in productive infections only, beginning at 10 h postinfection (p.i.) and reaching maximal levels by 20 h p.i. The rate of viral DNA synthesis in the productive cells was maximal between 8 to 16 h postinfection, and only low levels of viral DNA were synthesized in T.ni cells. The data suggest that the productive SfMNPV/S.frugiperda cell infection has a gene expression program similar but not identical to that of Autographa californica MNPV infections. The SfMNPV/T.ni cell infection is nonpermissive and is restricted at the earliest phase of the viral gene expression program. PMID- 2248551 TI - Analysis of polypeptides synthesized in bovine respiratory syncytial virus infected cells. AB - Ten virus-specific polypeptides ranging in molecular weight from approximately 200k to 11k were identified in bovine respiratory syncytial virus (BRSV-)infected cells. Time course analysis of the induction of the viral polypeptides indicated that they could be detected as early as 30 min post-infection and their synthesis reached a plateau 12 h after infection. Cell free translation of total infected cell mRNA in a rabbit reticulocyte system yielded 7 proteins corresponding in size to virus-specific proteins synthesized in BRSV-infected cells. The P protein was highly phosphorylated; G and F were identified as glycoproteins by [3H]glucosamine labeling. Glycosylation of G protein was largely resistant to tunicamycin, suggesting that the majority of the carbohydrate residues are attached via O-glycosidic bonds, whereas the F protein was N-linked glycosylated. Tunicamycin caused a drastic reduction in the yield of infectious virus titer indicating that the carbohydrate moieties serve a critical role in the infectious cycle of BRSV. PMID- 2248552 TI - Relationship between the levels of biological indicators of lead exposure in children and their mothers environmentally exposed to lead. AB - From a follow-up study (1976-1985) on lead exposure in population groups living in the vicinity of a lead smeltery, and those from a control area, data were selected on 222 simultaneous measurements of biological indicators of effective lead exposure (absorption) in the blood of children and their mothers. The range of lead exposure levels in both the children and the mothers was very wide (from "normal" to largely excessive lead exposure) as indicated by blood lead (PbB), activity of delta-aminolaevulinic acid dehydratase (ALAD) and erythrocyte zinc protoporphyrin (ZnPP). A highly significant (P less than 0.001) exponential decrease in ALAD with respect to PbB, as well as an exponential increase in ZnPP with respect to PbB, was found in children and their mothers. Highly significant (P less than 0.001) relationships were found between the levels of PbB, ALAD, and ZnPP in the children with respect to those found in their mothers, indicating the relevant influence of a similar microenvironment (e.g. lead in indoor air and in household dust) and life-style (e.g. household hygiene habits and food preferences) on the level of effective individual lead exposure. Although these relationships have indicated generally higher levels of lead in children with respect to their mothers, the hypothesis of a relatively higher absorption and retention of lead in children of a lower age than that in children of a higher age could not be confirmed, which is in agreement with our previous observations. However, when the three subgroups according to the age of the children were compared (i.e. 0.3-4.5 years, 5-10 years, and 10.5-15 years), it appeared that children aged 0.3-4.5 years had the lowest lead absorption and those aged 5-10 years the highest in relation to their mothers. Within each of these subgroups, a tendency towards relatively higher effective lead exposure in children (i.e. the child/mother ratio of PbB, ALAD and ZnPP levels) with respect to an increase in environmental lead exposure level has been observed. PMID- 2248553 TI - [Immunologic status, respiratory symptoms and ventilatory function in fur processing workers]. AB - A group of 54 women employed in the fur processing industry and a control group of 31 non-furriers were examined. The highest prevalence of positive immediate skin reactions to antigen from animal hair was found for marten (10%), followed by fox and lamb (7%), mink (5%) and chinese lamb, domestic fox and chinese calf (2%). Precipitating antibodies were demonstrated for lamb (17%), astrakhan (14%), mink, domestic fox and for skunk (12%), chinese lamb (10%), and chinese calf (7%). Increased total IgE was found in 9.5% of the furriers. Chronic respiratory symptoms were more prevalent among workers with positive skin tests and positive precipitins than among those with negative tests. The prevalence of the acute symptoms was higher among workers with precipitins than in those without them. There was no such relationship between the symptoms and the results of skin tests. Acute reductions of ventilatory capacity over the work shift occurred in workers with positive precipitins but not in those with positive skin tests. Our study suggests that furriers can develop acute and chronic respiratory difficulties frequently associated with specific indicators of atopy. PMID- 2248554 TI - [Noise as a risk factor for arterial hypertension in sailors]. AB - Analysis of the prevalence of arterial hypertension among seamen using the chi square test did not show a difference between the engine-room personnel (n = 80) exposed to elevated total ship noise levels (103 +/- 4.6 dB) and the rest of the crew (n = 119) exposed to lower noise levels (63 +/- 4.6 dB), or between the engine-room personnel and the control group (n = 108) exposed to lower levels of occupational noise (64-72 dB). The number of persons with hypertension was higher among the rest of the crew than among the controls. According to Student's t-test there was no difference in systolic or diastolic blood pressure levels between the two groups of seamen. In both these groups blood pressures were higher than in the control group. Among the seamen not working in the engine-rooms and in the subpopulations of both groups of seamen the number of hypertensive persons was greater among those with a noise-induced hearing loss than among those without it. Of the features which could be connected with arterial hypertension and are known to be risk factors of atherosclerosis (age, length of service, body mass index, body fat percentage, plasma cholesterol, triglycerides and glucose, cigarette and alcohol consumption, psychic tension index and recovery time in Lorenz test), only the body mass index could have caused the marked differences in blood pressures between seamen and the controls. The degree of hearing loss correlated with systolic blood pressure in both groups of seamen as well as with diastolic blood pressure in the engine-room personnel. The results of the study do not allow to draw a clear conclusion regarding correlation between ship noise and arterial hypertension, although some indicators point to a certain effect of noise on blood pressure. PMID- 2248555 TI - [Ethylene glycol poisoning treated with hemodialysis]. AB - The paper deals with the course of illness in a patient aged 56 years who had ingested accidentally an unknown amount of alcoholic drink followed by 150 ml of 95 percent solution of ethylene glycol. The patient was admitted to the intensive care unit 28 hours after the accident. The serum ethylene glycol concentration reached 14 mg/100 ml. The slow elimination of ethylene glycol during 28 hours before haemodialysis could be explained by the protective effect of ethanol which the patient had consumed before ethylene glycol. The method of extracorporeal haemodialysis was applied for four hours; the membrane surface was 1.3 m2 and blood velocity 200 ml/min. The rate of clearance of ethylene glycol and its metabolites was 110-150 ml/min. The total amount of ethylene glycol eliminated during four hours of haemodialysis came to about 5 g. Four hours from the beginning of the treatment the serum ethylene glycol concentration was not measurable. As the patient developed signs of acute renal failure the haemodialysis method was applied two more times. The patient was dismissed from hospital in good clinical condition, with normal diuresis and repaired renal function on the 13th day from admission. PMID- 2248556 TI - [Scientific basis and professional concept of instituting a medical program of active recreation]. AB - Physical activity is essential to health and should be exercised in accordance with one's functional and health state. Among the most advanced forms of programmed physical activity is medically programmed active leisure (MPAL). The implementation of MPAL in practice relies on research and on scientifically based concepts and attitudes which control the selection of persons for and their inclusion in MPAL. In Croatia MPAL is a form of specific care for worker's health, which is conducted in compliance with the health care and health insurance acts. PMID- 2248557 TI - [The effects of chromium on human health]. AB - This is a review of studies dealing with the physiological role of chromium in the body and its harmful effects to human health. Trivalent chromium is discussed as a trace element essential to normal metabolism of hydrocarbons and to functioning of some enzymes. Toxic and carcinogenic effects of chromium due to occupational exposure, environmental pollution, food contamination and accidental poisoning are described. PMID- 2248558 TI - Interactions between cultured bovine arterial smooth muscle cells and endothelial cells; studies on the release of growth inhibiting and growth stimulating factors. AB - The balance of growth stimulating and growth inhibiting factors in the arterial wall might be of importance in the pathogenesis of atherosclerosis. A method using different dialysis steps was used to allow the simultaneous study of micromolecular (dialysable) and macromolecular (non-dialysable) substances in conditioned media from bovine and human arterial endothelial cells and smooth muscle cells in culture. Micromolecular substances inhibited the proliferation of aortic smooth muscle cells and endothelial cells, while the macromolecular substances were growth stimulating. The effect of the micromolecular and macromolecular factors was dose dependent, but only the micromoleculars were affected by conditioning time. The micromoleculars were heat stable. The effect of macromoleculars was completely abolished by heating to 100 degrees C for 5 minutes. Confluent cells released relatively more growth inhibiting and less growth stimulating activity while the balance was changed in subconfluent cells showing an increased release of growth stimulating activity per cell. A co culture model for endothelial and smooth muscle cells demonstrated that the confluent aortic endothelial cells released relatively more growth inhibiting activity. These models seem suitable for the study of interactions of growth inhibition and stimulation between arterial cells in vitro in the normal or pathological state. PMID- 2248559 TI - The fatty acids of platelets and red blood cells in urban black South Africans with myocardial infarction. AB - The occurrence of myocardial infarction (MI) in Black South Africans, while poorly documented, is believed by many to be approximately one-tenth that of White South Africans. Recently, this disease has been reported to be increasing in the urban Black South African population. In order to determine if variations in dietary habit within the urban black community are contributing to the disease occurrence, the fatty acid content of whole platelets and red blood cells (RBC) were measured in 25 urban Black Africans with documented history of MI. These values were compared to an asymptomatic Black African control group. Total saturated fatty acids were increased and total polyunsaturated fatty acids (PUFA) were decreased in the patient's platelets. Stearic acid (18:0) was significantly increased and eicosapentaenoic acid (20:5 n-3) was slightly but significantly decreased in the patient's platelets. No difference was seen in the total saturated and total unsaturated fatty acid levels of red blood cells (RBCs). Only 20:5n-3 and 22:5n-3 were slightly but significantly decreased in the patient's RBCs. Similarities in RBC fatty acids indicate that the progression of MI in this population may not be related solely to changes in dietary habits. PMID- 2248560 TI - Skin cancer control in the 1990s. PMID- 2248561 TI - Preventive medicine in general practice. PMID- 2248562 TI - Current thinking on fibromyalgia syndrome. AB - Fibromyalgia (fibrositis) syndrome (FS) is a common and chronically painful form of non articular rheumatism. A high count of tender points is characteristic, but there are no confirmatory laboratory tests--the diagnosis is clinical. The cause is unknown, although a number of recognised factors are important in the expression of the condition. PMID- 2248563 TI - Spondyloarthropathies. AB - The spondyloarthropathies are disorders characterised mainly by sacroiliitis (with or without spondylitis), peripheral oligoarthritis, enthesopathy, absence of rheumatoid factor, certain extra-articular features such as iritis, and increased prevalence of HLA-B27. The diagnosis should be considered in patients, especially young people, with low back pain. A history of psoriasis, bowel dysfunction, eye problems and peripheral joint inflammation should point to the diagnosis. PMID- 2248564 TI - Arthralgia: a diagnostic strategy. AB - For arthritis or arthralgia there is no simple system for diagnostic analysis, but whether it is polyarthritis or monoarthritis, acute or chronic in onset, some general rules apply. Common causes include osteoarthritis (primary and secondary) and viral infection. Drugs should be considered, including those inducing gout. It is still imperative not to miss rheumatic fever, sepsis and tuberculosis in assessment. We may encounter more cases of Lyme disease presenting as arthritis. PMID- 2248565 TI - Polyarthritis. A diagnostic approach. AB - The authors discuss the general classification of rheumatic disorders and the likely diagnosis of polyarthritis based on the mode of presentation, the patient's clinical situation and appropriate investigations. There is no simple formula that will lead to the correct diagnosis and specific therapy for every patient. PMID- 2248566 TI - Procedural skills for general practice. The results of a Queensland survey. AB - The acquisition of procedural skills for general practice, appears to be somewhat haphazard. A list of 139 procedural skills of possible use to a GP was compiled. A survey of sixth year medical students, faculty and hospital teaching staff, and GPs in Queensland was undertaken to evaluate the perceived importance of these skills. The list has been modified to 47 'essential' and 22 'essential or desirable' skills, and could form the basis for more directed learning in the area of procedural skills. PMID- 2248567 TI - Caring for the developmentally disabled in the community. AB - As deinstitutionalisation programmes take effect, more and more developmentally disabled people are living in the community. They are becoming patients of general practitioners who need to be aware of some of their special health problems. Primary care of disabled people presents particular challenges and rewards for the interested family doctor. PMID- 2248568 TI - The use of fetal kick charts. AB - This article recommends and reinforces the usefulness of fetal movement charts or 'kick charts' for GP obstetricians. It highlights the importance of adequate explanation to the women using the fetal movement charts (FMC) so that they are aware of why they are counting kicks and what is hoped to be achieved with the use of the FMC. Explanations are also given of problems encountered with the charts. PMID- 2248569 TI - The management of hypertension in Queensland general practice. AB - This survey indicates that hypertension in Queensland is primarily treated by general practitioners. It suggests a real need for a professionally endorsed information package for general practitioners and overwhelmingly points to the need for lifestyle information for patient use. It also identifies the elderly as a special treatment group. PMID- 2248570 TI - Patient education. Plantar fasciitis. PMID- 2248571 TI - Painless injection technique. PMID- 2248572 TI - Tenpin bowler's thumb. PMID- 2248573 TI - A malignant reaction to trifluoperazine (Stelazine). PMID- 2248574 TI - Syndrome quiz. Maternal phenylketonuria. PMID- 2248575 TI - It's all in the genes. PMID- 2248576 TI - Recapping needles. PMID- 2248577 TI - The hazards of city driving. PMID- 2248578 TI - The male menopause. Fact or fancy? AB - Men over 50 may experience a decline in sexual, physical and intellectual potency. In many respects this is analogous to the menopause, hence the term male menopause. Although this term suggests profound hormonal changes and loss of reproductive capacity these do not occur in men. The hormonal changes are subtle and loss of fertility is relative. Other changes, part of normal ageing, include degeneration of neural tissue, arterial occlusion and loss of tissue turgor. PMID- 2248579 TI - Vasectomy in review. AB - In Queensland 60 per cent of vasectomies are performed by general practitioners. Recent statistics are reviewed and suggest a guide to the selection of men for the operation. Improvements in the technique, which increase the possibility of successful reversal, and which speed the testing for sterility, are discussed, and will be described in detail in a second article. PMID- 2248580 TI - Sexual myths in the male. AB - Most men, regardless of intelligence and education, have their sexual behaviour adversely affected by a variety of misconceptions or myths. Much sexual unhappiness results. In this article the commonest misconceptions and some of their adverse effects are examined. PMID- 2248581 TI - The fit male adolescent. AB - Adolescence is a normal developmental phase that can be experienced with confidence and optimism if it is anticipated as a time of challenge and of growth. The characteristics of adolescent thinking and affect are considered and the challenges that the fit adolescent must overcome are reviewed. Factors that protect against things going wrong are discussed. PMID- 2248582 TI - The combined oral contraceptive. A practical guide. AB - Prescribing the combined oral contraceptive pill is a rewarding combination of hands-on clinical medicine, logical therapeutics, prevention, and patient education. Lowest dose with the least side-effects is the overriding principle of prescribing. It is important to spend time teaching patients and partners how to manage their pill-taking and to be responsible for their medication and prevention follow up. PMID- 2248583 TI - Common problems. Tiredness. AB - When a patient presents with tiredness, the diagnostic model is a useful basis for considering the probable diagnosis. At the same time it is imperative not to overlook the serious, even life threatening, causes such as malignant disease or AIDS. Such an organised approach allows the practitioner to ask the correct questions because, as always, the quality of the history taking is vital in leading to the diagnosis of this difficult symptom. PMID- 2248584 TI - Ron Elisha. General practitioner and playwright. AB - Australian Family Physician is privileged to present a regular feature on notable Australian doctors. We are aware that there are hundreds of doctors whose service to their patients and dedication to their vocation make then outstanding people and excellent role models. This feature will present profiles on doctors who have contributed something special in their careers whether it be excellence of service or an additional special skill or achievement other than medical. We hope that readers enjoy learning about their colleagues and invite you to let us know about any members of our profession who would be worthy inclusions in this feature. PMID- 2248585 TI - Aortitis in general practice. PMID- 2248586 TI - Influences. PMID- 2248587 TI - Patient education. Testicular of examination (TSE). PMID- 2248588 TI - Emergency eye injuries. AB - This study analyses all patients presenting with eye complaints to the casualty section of a Brisbane Hospital during a one month period. Eye complaints constituted 3.6 per cent of all patients. A foreign body was involved in 57 per cent of all eye injuries. The patients were subject to a trial assessing the effectiveness of antibiotic treatment following removal of the foreign body. There was no significant difference between antibiotic and placebo (sterile saline). PMID- 2248589 TI - Too big for their boots. PMID- 2248590 TI - Diagnosing a fracture. PMID- 2248592 TI - Appetite and infectious mononucleosis. PMID- 2248591 TI - Storing polio vaccine. PMID- 2248593 TI - Doubts about asthma drug. PMID- 2248594 TI - The endocrinology of conception. PMID- 2248595 TI - Placental steroid hormones. AB - The intent of this review was a selective consideration of recent advances in understanding placental steroidogenesis in humans. While we have omitted material, both intentionally and unintentionally, we hope this discourse presents a flavour of the current molecular endocrinology of placental steroidogenesis. In particular, advances in knowledge as it relates to the enzymes involved in progesterone and oestrogen metabolism have been addressed and correlated with placental development. Finally, because relatively less is known about regulation of steroidogenesis in the human placenta beyond the aspects of growth and differentiation, we have discussed regulation in general terms using recent data obtained in animal species. PMID- 2248596 TI - Prolactin and related peptides in pregnancy. AB - This brief review has attempted to portray the complex involvement of prolactin in pregnancy. Pituitary prolactin production and lactotroph proliferation are markedly affected by oestrogens and pregnancy. Enlargement of pre-existing prolactinomas may occur during pregnancy induced with dopamine agonist drugs, and this can be a major clinical problem with larger tumours. Prolactin is produced by late luteal and decidualized endometrium as well as by the pituitary gland, but much less is known about its secretory regulation or its function. The family of prolactin-related protein hormones is rapidly expanding with the recognition of placental lactogens, variant growth hormone, proliferin, decidual luteotropin, and at least two further prolactin-related peptides in rodents. This complex system of related but distinct protein hormones, with different temporal patterns of production during gestation, suggests an important physiological role, but it remains to be seen to what extent they are involved in placental function itself, maternal metabolism or fetal growth. PMID- 2248597 TI - Diabetes and diet in pregnancy. AB - The mean additional energy requirement for pregnancy has been calculated at 285 kcal daily and it reflects the energy needs for production of the fetoplacental unit and for the maternal physiological adaptations to pregnancy. In practice there is considerable variation in energy requirement due to alterations in maternal energy expenditure. Optimal energy intakes are dictated also by the pre pregnancy maternal weight. The outcome of pregnancy is improved in the underweight mother by an intake which produces a weight gain in pregnancy of approximately 14 kg, whereas a rise of only 7 kg may be optimal for the obese mother. Obesity with or without diabetes is associated with macrosomia and other problems and it is sensible to attempt to limit weight gain in pregnancy at a time when maternal motivation is high. Diabetes in pregnancy may arise in patients with pre-existing NIDDM or IDDM, but more commonly it is diagnosed for the first time during pregnancy and it usually disappears after delivery (gestational diabetes). Recent evidence suggests that gestational diabetes has a strong genetic component and is usually NIDDM precipitated early in life by the pregnancy. Both gestational diabetes and NIDDM are characterized by insulin deficiency and by insulin resistance. Long-term follow-up studies have demonstrated that NIDDM or impaired glucose tolerance develop in later life in 50 70% of women with previous gestational diabetes. The adverse effects of pregnancy on the mother with pre-existing diabetes may be minimized by good diabetic control as may be adverse effects on the fetus and neonate of diabetes in the mother. An increased incidence of fetal malformations persists in pregnancies with pre-existing maternal diabetes. Diabetes of any form may be associated with neonatal hypoglycaemia. The aim of therapy is to produce maternal normoglycaemia throughout pregnancy by dietary measures and insulin treatment if required. Women with pre-existing diabetes should tighten their blood glucose control from before conception. Optimization of insulin therapy and diet are required for IDDM and most NIDDM women will require insulin treatment in pregnancy. Gestational diabetics require diet and possibly insulin. Most pregnancies now proceed to term. PMID- 2248598 TI - Endocrine disease and pregnancy. PMID- 2248599 TI - The endocrinology of parturition in the human. AB - Current evidence suggests that oestrogens, progesterone, relaxin, the prostaglandins, and oxytocin are all hormones concerned to a major degree with the onset and maintenance of parturition. Oestrogens, relaxin, and the prostaglandins are particularly involved with cervical ripening, while prostaglandins, progesterone and oxytocin are more involved in regulating myometrial contractility. Catecholamines may also have some regulatory function in relation to uterine contractions. Progesterone dominance during pregnancy is associated with a firm closed cervix, few myometrial gap junctions, low calcium levels in the cells, and a quiescent myometrium. At term, a change in the oestrogen/progesterone balance favours cervical ripening and increased uterine activity. Of particular importance at the level of the muscle cell are changes in the number of oxytocin receptors; a complex interaction between cAMP and phosphoinositide metabolism governs the intracellular level of calcium, thus regulating contractile activity. PMID- 2248600 TI - Hormonal and developmental regulation of pulmonary surfactant synthesis in fetal lung. AB - Pulmonary surfactant, a unique developmentally regulated, phospholipid-rich lipoprotein, is synthesized by the type II cells of the pulmonary alveolus, where it is stored in organelles termed lamellar bodies. The principal surface-active component of surfactant, dipalmitoylphosphatidylcholine, a disaturated form of phosphatidylcholine, acts in concert with the surfactant-associated proteins to reduce alveolar surface tension. Relatively large amounts of phosphatidylglycerol also are present in lung surfactants of a number of species, including man. The role of phosphatidylglycerol in surfactant function has not been elucidated; however, its presence in increased amounts in pulmonary surfactant is correlated with enhanced fetal lung maturity. Surfactant glycerophospholipid synthesis in fetal lung tissue is regulated by a number of hormones and factors, including glucocorticoids, prolactin, insulin, oestrogens, androgens, thyroid hormones, and catecholamines acting through cyclic AMP. In studies with human fetal lung in organ culture, we have observed that glucocorticoids, in combination with prolactin and/or insulin, increase the rate of lamellar body phosphatidylcholine synthesis and alter lamellar body glycerophospholipid composition to one reflective of surfactant secreted by the human fetal lung at term. Four surfactant-associated proteins, SP-A, SP-B, SP-C and SP-D, have recently been characterized. Recognition of their potential importance in the reduction of alveolar surface tension and in endocytosis and reutilization of secreted surfactant by type II cells has stimulated rapid advancement of knowledge concerning the structures of the surfactant proteins and their genes, as well as their developmental and hormonal regulation in fetal lung tissue. The genes encoding SP-A, SP-B and SP-C are expressed in a cell-specific manner and are independently regulated in fetal lung tissue during development. SP-A gene expression occurs exclusively in the type II cell and is initiated after 75% of gestation is complete. In the human fetus, expression of the SP-B and SP-C genes is detectable much earlier in development than SP-A, before the time of appearance of differentiated type II cells. It is apparent from studies using human and rabbit fetal lung in culture that cyclic AMP and glucocorticoids serve important roles in the regulation of SP-A gene expression. While the effects of cyclic AMP are exerted primarily at the level of gene transcription in human fetal lung tissue, glucocorticoids have stimulatory effects on SP-A gene transcription and inhibitory effects on SP-A mRNA stability. In addition, cyclic AMP and glucocorticoids act synergistically to increase SP-A gene transcription in human fetal lung in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2248601 TI - Physiology of lactation. AB - The development of the human breast is dependent on the presence of ovarian steroids. The basic secretory units--the alveoli--continue to respond to steroids throughout the reproductive years. Lactogenesis is triggered by a rapid and drastic fall in progesterone at delivery and maintained by prolactin while the actual expulsion of milk from the breast depends on oxytocin. The composition of milk is very variable but is adequate to provide the sole source of nutrients for up to the first 6 months of life. Lactation suppresses ovarian activity probably through a disturbance in the pulsatile pattern of LH secretion but the degree of suppression depends on infant feeding patterns and perhaps on maternal nutritional status. Breastfeeding therefore confers a degree of protection against pregnancy but some artificial methods of contraception are appropriate for use during lactation. It is still not clear whether breastfeeding protects significantly against breast cancer. PMID- 2248602 TI - [Allogeneic lyophilized fascia lata "soft" as extra-articular stabilizer in simple and complex knee joint instability]. AB - 50 operative procedures in capsular-ligamentous apparatus of knee joint were done from 1.9.1988 until 31.12.1989 among 209 in charged treated sports injuries. The multiplicity in pattern of injuries is the reason for individual procedure in reconstructive joint-surgery and because of this various indications for auto- and allogenic eg. synthetic materials, static and dynamic procedures else free or vascularized grafts. The lyophylized fascia lata "soft" is used in case of anteromedial instability, isolated medial rupture of collateral ligament of the first degree else for augmentation after primary treated medial injury of collateral ligament. Early results are proving the histocompatibility, the healing without complications else timely stability and recommending the fascia lata-plasty in given indications. PMID- 2248603 TI - [Formaldehyde-fixed human varicose vein bioprosthesis with siliconized inner surface for hemodialysis. Clinical analysis of 165 transplants]. AB - With the submitted study of 165 HVV-vessel-transplantations the marking properties like reduced immunogenity, primary athrombogenicity, form fixated vascular lumen, ability for punction, flow reduction and stability for storage were possible to prove. Few complications (thromboses, aneurysms, infections) and also low rate of revision marks the long-term progress of this bioprosthesis. It will be stated with emphasis, that the use of this vascular device is indicated, if the patient's veins for creation of an arteriovenous vascular access is not available. In long-term progress the rate of function is better in comparison with other similar or synthetic materials for prostheses. PMID- 2248604 TI - Possible virus contaminants in tissue banking. AB - The importance of transplantation in clinical medicine is still increasing. Risks by transmission of infections agents by virus contaminated transplants with following diseases are most feared. Anamnesis and course of spectacular cases by unconventual viruses (Creutzfeld-Jakob), pathogens of AIDS and rabies and transmission by different routes have been analysed. The necessity of legal directives for blood and tissue banks has to be stressed. PMID- 2248605 TI - [Personal experiences with covering burns in children with amnion]. AB - The different methods of local treatment of burns are still controversial. Aims of good local are the therapy prevention of fluid loss, loss of proteins, electrolytes, heat and energy, prevention eg. reduction of wound infections, preservation and acceleration of regeneration of remained own skin, influence on good formation of scars eg. preparing of high value as possible transplant-ground for eventual necessary skin transplantation. Experience in covering juvenile burn injuries with lyophilized Human-Amnion were gathered in our department for more than 15 years. The treatment of patients with this "biological bandage" and results were demonstrated. In our opinion the method of primary amnion covering of juvenile burn-injuries is superior to other procedures. PMID- 2248606 TI - Use of dura mater allografts in operations of abdominal wall hernias. AB - Treatment of large and recurrent abdominal wall hernias represents a rather complicated problem in surgical tactics and technique. In an effort to overcome the shortage of autogeneic material for strengthening the abdominal wall it is possible to substitute the defect by different synthetic or biological materials. Our experience with the use of freeze-dried dura mater is dealt with. The total of 18 allogeneic grafts were used in 11 patients with ventral hernias. The therapeutic procedure and clinical results are reported. Minor complications have developed in 2 patients, but they did not influence the good results of surgical treatment. PMID- 2248607 TI - [Indication for and results of the application of glycerol-preserved homologous split-thickness skin following burns]. AB - Since 1983 the treatment of second-degree burns with glycerol-conserved allogenic split-thickness skin grafts is published. In case of actual problems with AIDS the gathering of split-thickness skin was modified and a new method for gaining split-thickness skin of organ-donors created to prevent the virus transfer. Because of these high security in contagiousness the skin graft transplantation with allogenic glycerol-conserved donor-skin in case of second-degree-burns was standardized in the Berlin Burn Center. To prevent the formation of granulation tissue after second-degree burns a tangential debridement of necrotic corium will be done in 1/10 mm thick slices on the third posttraumatic day and the defects covered with 1:1.5 mesh grafts extended. The results of 267 patients in 1988 and 1989, who were treated in accordance to this regimen, will be demonstrated. In 11% of cases the alloplastic skin graft in adults was not rejected 6 month after transplantation and in 2% of cases the depth of burn was not estimated properly and hypertrophic scars had to be excised and covered with autogenous split thickness skin. General second-degree-burn healed after debridement and covering with allogeneic split-thickness skin without formation of hypertrophic scars. PMID- 2248608 TI - [Experiences in the application of tissue transplants in Butzow district hospital]. AB - In 15 years 63 Transplantations were done. 17 times with autogenous and 46 times with allogeneic transplants. Main indications were relapsed- and scar herniations, ruptures of achilles tendon and acromio-clavicular luxation. Advantages of allogeneic transplantation in comparison with autogenous transplantations will be demonstrated. It is referred to the consistent use of principles of aseptic, antiseptic and the careful atraumatic surgical technique in transplantation. PMID- 2248609 TI - [Results of Keller/Brandes method of hallux valgus surgery]. AB - In 1983 to 1987 we operated 216 Patients on hallux valgus. In most of them we made the method of Keller/Brandes. This is a report about the results of 165 patients with 238 operated hallucis. PMID- 2248610 TI - [Surgical scoliosis therapy using VDS and Harrington instrumentation (ventral derotation spondylodesis)]. AB - The VDS-method in accordance to Zielke and the Harrington-distraction spondylodesis are proved as methods for correction of scoliosis lasting for decades, which late results are world-wide analysed and published. The both diametrical corrective principles and the fundamental different operative techniques settle their different indications, which doubtless depend on the experience of the surgeon. Both methods complete each other in operative spectrum of the spinal surgeon. A careful study of the bending properties and the general situation is the supposition for adequate differential indication, which details and results are reported. PMID- 2248611 TI - [Training-induced changes of reference vectors in the QRS complex of the EKG of young trotting horses]. AB - After the onset of training ("breaking") in young standardbred horses within continuing investigations changes of vectors in the QRS-complex were considered. These changes accomplished in two stages. Mainly within the first three months of training the vector R (VR) in limb leads changed to the left and to caudal and dorsal. In a second interval between five and seven months after breaking the vector S (VS) changed to cranial. As main cause the different character of training in both phases is discussed. Additional indicators of age- or development-related causes were not found. PMID- 2248612 TI - [The absorption of colostral immunoglobulins in newborn piglets. I. Effect of time from birth to the first feeding]. AB - The effects of a delayed onset of feeding on the absorption of intact immunoglobulins from the small intestines was investigated in newborn piglets by using an automatic device ("artificial sow"). Fasting periods extended to a maximum of 24 hours and were followed by 12 hourly allotments of 25 ml of sow colostrum. The concentrations of immunoglobulins G, A and M were analyzed in plasma samples drawn before and after the onset of feeding. The capacity for Ig absorption was not impaired by the fasting. The same plasma levels of 12 and 18 hours after the onset of feeding were obtained in piglets fed immediately after birth as observed with individual variations in all experimental groups, for which we could find no explanation. Our results indicate, that the absorptive ability of the intestinal epithelia for immunoglobulins is not timed from birth but rather from the onset of feeding. PMID- 2248613 TI - [The development of a residue-poor anesthesia in swine]. AB - The intention of this study was to develop an intramuscular injectable anesthesia for swine. Therefore the clinical signs of several sedative or anesthetic drugs and their combinations were tested. The combinations of the phencyclidines ketamine and tiletamine with different benzodiazepines were most effective. The phencyclidines induced a rapid immobilisation of sufficient length. The benzodiazepines produced muscle relaxation, prolonged the immobilisation and suppressed the side effects of the phencyclidines like excitation. The analgetic action of the combinations were insufficient. Trials to improve analgesia by supplementation with opiates were only in the combination ketamine/climazolam/levomethadone successful. In other combinations opiates caused postanesthetic excitations with hyperthermia. The trials to improve the analgetic effect by combining tiletamine/zolazepam with imidazolidine-derivatives were only partly successful. But the tiletamine/zolazepam/imidazolidines combinations caused severe hypothermia and other side effects. Because of postanesthetic excitations, the combination of ketamine with xylazine can not be recommended as a good anesthesia for swine. The action of ketamine with azaperone or different phenothiazine-derivatives was insufficient. PMID- 2248614 TI - [Several physiologic aspects of the reactions of foals in the first three days after weaning]. AB - Changes have been observed in nine foals, six months of age, after weaning for the time of three days, namely in the intake of drinking water, hematocrit, sedimentation of erythrocytes and three minerals Na+, K+ and Cl-. Foals respond to weaning immediately, lowering significantly their consumption of drinking water and increasing high significance of Na+ and Cl-. Changes of level K+, hematocrit and sedimentation don't show any significant variations. The results reached are to be considered as an introductory information for further inquiry on the more extensive methodical basis. PMID- 2248615 TI - [The functional and hygienic evaluation of a thermal exchange storage apparatus for recovering warmth from outgoing stable air]. AB - By means of a thermo exchange apparatus it is possible to recover 70 to 80 percent of warmth of the stable air for heating. Thus much energy for climatizing can be saved. Alternating directions of to and from air streams may cause re influx of germs, dependent on percentage of dust. This risk can be minimized by using an apparatus each for relatively small units separately. PMID- 2248616 TI - Plasma apolipoprotein E, high density lipoprotein1 (HDL1) and urinary mevalonate excretion in pancreatectomized diabetic dogs: effects of insulin and lovastatin. AB - Hypercholesterolemia and increased concentrations of an apolipoprotein E (apoE) containing HDL subclass, high density lipoprotein1 (HDL1) have been observed in streptozocin-alloxan diabetic dogs consuming normal amounts of dietary cholesterol. The aim of this study was to characterize the response of HDL1 and its targeting ligand, apoE, to insulin and HMG-CoA reductase inhibitor treatment in pancreatectomized diabetic dogs. Following induction of diabetes, plasma total cholesterol, HDL1, and apoE concentrations were all increased. Urinary mevalonate excretion, an index of cholesterol synthesis in humans, was 6-fold that of nondiabetic controls. Lipoprotein fractionation by Pevikon block electrophoresis and gel filtration chromatography showed that the increased cholesterol and apoE were associated with alpha 2-migrating particles corresponding to HDL1. Insulin treatment, resulting in near normal fasting blood glucose concentrations in the group as a whole (average 5.1 mM, 92 mg/dl), led to variable reductions in apoE, total plasma cholesterol, and HDL1. Uncorrected dyslipidemia during intensified insulin treatment appeared to be related to failure to achieve euglycemia. Despite unremitting hyperglycemia, treatment with lovastatin resulted in pronounced decreases in plasma cholesterol, HDL1 and apoE to concentrations below those observed in nondiabetic animals. Mevalonate excretion also fell, but remained twice normal. Thus neither modality corrected all of the abnormalities in canine diabetic dyslipidemia. Since apoE-containing HDL1 may mediate cholesterol traffic between the periphery and the liver (reverse cholesterol transport), the present observations suggest that increased cholesterol synthesis is accompanied by parallel abnormalities in cholesterol flux through the reverse transport pathway in the canine model. PMID- 2248617 TI - Sodium oleate promotes a redistribution of cholesteryl esters from high to low density lipoproteins. AB - Cholesteryl esters readily exchanges between the low density lipoproteins (LDL) and high density lipoproteins (HDL) in human plasma in a process of equilibration catalysed by the cholesteryl ester transfer protein (CETP). In the present studies, in which mixtures of human LDL and HDL have been incubated in vitro with partially pure CETP, it has been found that Na oleate disrupts the CETP-mediated equilibrium between LDL and HDL and promotes a concentration dependent redistribution of cholesteryl esters from HDL to LDL. The end result of the redistribution is the appearance of a cholesteryl ester enriched LDL fraction and an HDL fraction which is protein-rich, lipid-depleted and markedly reduced in particle size. PMID- 2248618 TI - Effect of hemodynamic factors on atherosclerosis in the abdominal aorta. AB - The distribution pattern of atherosclerotic plaques in the human abdominal aorta is examined using autopsy specimens. The location of the plaques is found to be dominant where flow separation may occur in the abdominal aorta based on hemodynamic theory. This observation provides strong support for the role of flow separation with subsequent platelet aggregation in atherogenesis. The severity of plaque formed in the anterior inferior wall of the abdominal aorta is found to be affected by the branching angles of the renal arteries as deduced from experimental results using glass tube models. PMID- 2248619 TI - Influence of serum triglycerides on the HDL pattern in normal subjects and patients with coronary artery disease. AB - The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL3 levels was found in any of the studied group. There was a clear negative correlation between HDL2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL3 flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk. PMID- 2248620 TI - Effects of probucol on plasma lipids and lipoproteins in familial hypercholesterolemic patients with and without apolipoprotein E4. AB - It has been reported that total cholesterol (Chol) response to probucol is greater in familial hypercholesterolemic (FH) patients with apo E4 than in those without apo E4. We further examined the effect of probucol on plasma triglyceride (TG) and lipoprotein-Chol levels as well as total Chol levels in heterozygous FH patients with apo E4 (n = 14 for apo E4/3, n = 1 for apo E4/4) and without apo E4 (n = 31 for apo E3/3). Probucol was administered in a dosage of 500 mg twice daily for 3 months. The reduction in total Chol levels was significantly greater in FH patients with apo E4 (-90 mg/dl, -27.5%) than in those without apo E4 (-41 mg/dl, -13.7%). The reduction in low density lipoprotein (LDL)-Chol levels was also significantly greater in FH patients with apo E4 (-73 mg/dl vs. -34 mg/dl). There was a significant difference in the change in TG and very low density lipoprotein (VLDL)-Chol levels with treatment between the FH patients with apo E4 (-37 and -8 mg/dl, respectively) and without apo E4 (+8 and +2 mg/dl, respectively). However, there was no significant difference in the reduction in HDL-Chol levels between the 2 groups (-9 mg/dl vs. -9 mg/dl). It is concluded that FH patients with apo E4 showed the greater reduction in plasma TG levels as well as total Chol levels with probucol treatment than those without apo E4, and that the greater reduction in total Chol levels in them, as reported previously, was mainly due to the greater reduction in LDL-Chol levels and slightly due to that in VLDL-Chol levels. PMID- 2248621 TI - Apheresis of low density lipoproteins using a heparin-based sorbent with low antithrombin III binding capacity. AB - A sorbent based on heparin fraction with low affinity for antithrombin III is proposed for low density lipoproteins apheresis in hypercholesterolemia. Heparin was fractionated on antithrombin III-Sepharose; fractions with high and low affinity for antithrombin III were immobilized on CNBr-activated Sepharose 4B. Both sorbents appeared to have an LDL-binding capacity essentially similar to that of the sorbent based on unfractionated heparin. However only plasmasorption on a low affinity heparin-containing sorbent did not reduce plasma antithrombin III. Hence the use of this sorbent may be advantageous over the currently applied sorbents with unfractionated heparin in the treatment of familial hypercholesterolemia. PMID- 2248622 TI - Aortic and lower limb artery calcification in type 2 (non-insulin-dependent) diabetic patients and non-diabetic control subjects. A five year follow-up study. AB - The purpose of the present study was to assess among a representative group of middle-aged newly diagnosed type 2 diabetics and control subjects the baseline prevalence and 5-year incidence of arterial calcifications of aorta and lower limb and their relationship to cardiovascular morbidity. The relationship of baseline risk factors to the development of arterial calcifications was also studied. At the time of diagnosis the age-adjusted prevalence of aortic and lower limb intimal calcifications was higher in diabetics than in control subjects (aortic calcifications: 29 vs. 17% for men, P = 0.05; 26 vs. 19% for women, P = 0.06; lower limb intimal calcifications: 24 vs. 12% for men, P = 0.02; 10 vs. 7% for women; P = NS), whereas no significant difference in baseline prevalence of lower limb medial calcifications was observed (15 vs. 21% for men, 9 vs. 10% for women). The 5-yr incidence of aortic calcifications in both sexes and of lower limb calcifications in men was similar in diabetic and control subjects, but the incidence of lower limb calcifications was higher in diabetic women than in control women (intimal: 33 vs. 11%, P = 0.009: medial: 29 vs. 14%, P = 0.05). The baseline prevalence of abdominal aortic (37 vs. 22%, P = NS for diabetics; 42 vs. 16%, P = 0.02 for control subjects), lower limb intimal (24 vs. 16% for diabetics, P = NS; 15 vs. 7% for control subjects, P = NS) and medial calcifications (23 vs. 7% for diabetics, P = 0.03) were higher in subjects who developed intermittent claudication during the follow-up than in those free of it at the 5-yr examination. Abnormalities in VLDL-metabolism and high systolic blood pressure were associated with the development of aortic calcification in diabetic subjects. In conclusion, already at the time of diagnosis atherosclerotic calcifications are more prevalent in type 2 diabetics than in nondiabetic subjects. During the follow-up diabetic women, but not men, had higher incidence of lower limb intimal and medial calcifications than non-diabetic subjects. Arterial calcifications tended to be associated with the development of intermittent claudication during the follow-up in diabetic and control subjects. PMID- 2248623 TI - Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation: reply to the letter of R.M.K.W. Lee. PMID- 2248624 TI - High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. AB - After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs = 0.659) between first-pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first-pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished. We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism. PMID- 2248625 TI - Nucleated erythrocytes in healthy infants and in infants of diabetic mothers. PMID- 2248626 TI - Tracheal suction and meconium: a proposed standard of care. PMID- 2248627 TI - Shoulder dystocia: prevention and treatment. AB - Although shoulder dystocia is an infrequent event it has assumed a position of great clinical importance because of our litigious environment. Many cases are preventable by the proper identification of risk factors, especially glucose intolerance, macrosomia, obesity, and postdate pregnancies. The severity of the problem can be rapidly graded or determined by the response to a systematic treatment plan; such a plan is outlined. PMID- 2248628 TI - Causalgic pain responding to epidural but not to sympathetic nerve blockade. PMID- 2248629 TI - Fragile X syndrome--an important cause of mental retardation. PMID- 2248630 TI - An integrated approach to evaluation of the solitary pulmonary nodule. AB - In this article, we describe an integrated approach for detection and evaluation of solitary pulmonary nodules. Initial evaluation of the solitary pulmonary nodule includes tomography, fluoroscopy, and comparison with previously obtained roentgenograms. Subsequently, thin-section computed tomography and phantom densitometry can be used for analysis, if indicated. The rationale for the use of computed tomography in the radiologic staging of bronchogenic carcinoma is to expedite and assist in the identification of the subset of patients with resectable tumors. For nonsurgical tissue diagnosis, fiberoptic bronchoscopy is generally the initial procedure for lesions 2.0 cm or larger in diameter, and transthoracic needle biopsy is used for those smaller than 2.0 cm. PMID- 2248631 TI - Rapid and complete resolution of giant cysticercal cysts after administration of praziquantel. A report of 4 cases. AB - Four patients with giant cysts, one cyst with a diameter of 55 mm, were treated with a 30-day course of praziquantel (Biltricide; Bayer-Miles) 50 mg/kg/d. One patient had corticosteroids administered simultaneously. All 4 patients had anticonvulsant cover. In all cases there was rapid and complete resolution of the cysts. In 2 patients this occurred within 30 days. The computed tomographic features of giant cysticercal cysts are: thin walled cystic lesions containing clear fluid, localised thickening of the wall (probably representing the scolex), absence of pericyst oedema, and the presence of associated smaller and more typical cysticercal larval forms. Giant cysticercal cysts resolve remarkably rapidly on medical therapy. A therapeutic trial of praziquantel can, in suspected giant cysticercal cysts, obviate the need for exploratory craniotomy. PMID- 2248632 TI - Knowledge resource preferences of family physicians. AB - Because of the pivotal role of medical knowledge in clinical problem solving, it is important to understand how clinicians decide to seek additional knowledge for patient care decisions and how they choose among the resources available to them. Using a self-administered questionnaire, 126 family physicians reported their use of 11 types of knowledge resources for answering patient-specific questions arising in clinical practice. They reported almost daily use of the Physicians' Desk Reference and more often than weekly use of colleagues. There was little use reported of Index Medicus or computer-based bibliographic retrieval systems. The research literature of medicine was used infrequently and rated among the lowest of resources in terms of credibility, availability, searchability, understandability, and applicability. In deciding among a subset of knowledge resources for answering a clinical practice question, resource cost variables related to clinical availability and applicability of the information to the problem at hand appeared to be more influential in the minds of physicians than factors related to quality of the resource. These findings have important implications for the development and deployment of knowledge resources intended to be useful and used in clinical practice. PMID- 2248633 TI - A description of eating disorders in 1932. AB - This article consists of a shortened and annotated translation of a paper on "An Interesting Oral Symptom Complex and Its Relationship to Addiction" by M. Wulff of Berlin, which was delivered before the German Psychoanalytic Society on April 12, 1932. The article describes four cases of an eating disorder in women that was characterized by binge eating, hypersomnolence, apathetic depression, and disparagement of the body image. After the eating binges, all four patients manifested periods of fasting, and two of the three, about whom such information is available, vomited. Translations of large excerpts of the case histories are presented together with a summary of Wulff's discussion. PMID- 2248634 TI - Prevalence of cardiovascular disease and diabetes mellitus in residents of Rochester, Minnesota. AB - To determine the prevalence of cardiac disorders as risk factors for stroke, we conducted a survey in 1986 in a stratified random sample of the population of Rochester, Minnesota, 35 years of age or older. The medical records of the 2,122 subjects in the sample were retrieved with use of the Rochester Epidemiology Project medical records linkage system. The data were used to estimate (1) the reliability of self-reported information about cardiac and cerebrovascular disorders and (2) the age- and sex-specific prevalence of diabetes mellitus and various cardiac and cerebrovascular conditions. The estimated prevalence for selected risk factors in the population 35 years of age or older was 5.8% for diabetes mellitus, 3.3% for myocardial infarction, 1.2% for mitral valve disease, 4.2% for left ventricular hypertrophy, and 2.8% for atrial fibrillation or flutter. These data can be used to estimate resources required for evaluation and management of the disorders. When the prevalence and the relative risk for stroke are known for a particular cardiac disorder, the proportion of stroke attributable to that disorder can be estimated. PMID- 2248635 TI - Hysterectomy for chronic pelvic pain of presumed uterine etiology. AB - This study evaluates the long-term outcome of 99 women who underwent hysterectomy for pelvic pain of at least 6 months' duration. All had symptoms and physical examination findings suggestive of disease confined to the uterus. Patients were excluded if there was previously documented extrauterine pelvic disease, extrauterine pelvic disease at the time of surgery, or uterine weight exceeding 200 g. Histopathologic analysis revealed leiomyomata in 12 (12.1%), adenomyosis in 20 (20.2%), and both leiomyomata and adenomyosis in two (2.02%). The average uterine weight was 91.1 g (range 24-198). Patients were followed after hysterectomy for an average of 21.6 months (range 15-64), with 77 of 99 (77.8%) showing significant improvement and 22 (22.2%) having persistent pelvic pain. Despite preoperative history and physical findings suggesting and histologic findings confirming uterine disease, nearly a quarter of the patients had persistent pelvic pain after hysterectomy for chronic pelvic pain. These findings should have a significant impact on the therapeutic choices recommended by gynecologists and may alter the informed consent that patients give in such cases. PMID- 2248636 TI - Should the complete medical record be computerized in family practice? An affirmative view. PMID- 2248637 TI - Endoscopic treatment of Dieulafoy's lesion of the duodenum. AB - Dieulafoy's lesion is an often unrecognized cause of catastrophic upper gastrointestinal hemorrhage, typically seen in otherwise asymptomatic patients. Although the lesion is most often found in the stomach, it has rarely been reported to occur in the jejunum and duodenum. Endoscopic treatment has recently been attempted to arrest the bleeding from these lesions, when found in the stomach, with satisfactory results. We report a patient with a bleeding duodenal Dieulafoy lesion who was successfully treated with endoscopic injection of epinephrine (1:10,000) and electrocoagulation. Endoscopic treatment of Dieulafoy's lesion should be attempted before surgery and, as in other causes of acute nonvariceal hemorrhage, be considered the treatment of choice. PMID- 2248638 TI - Role of glycolipids in the metastatic process: characteristics of neutral glycolipids in clones with different metastatic potentials isolated from a murine fibrosarcoma cell line. AB - We investigated whether metastatic phenotype is associated with a characteristic glycolipid pattern. For this study, we developed a system of variants with different metastatic potentials that we isolated from the highly metastatic T3 murine fibrosarcoma line by culture in 0.3% agar or on plastic. The glycolipid profiles of T3 cells and of their highly metastatic isolates were characterized by a high level of globotriaosylceramide (Gb3ose). On the other hand, Gb3ose was reduced in a weakly metastatic clone isolated from T3 cells. A reduced level of Gb3ose was also found in a weakly metastatic subclone isolated from a highly metastatic T3 clone. Propagation of this subclone led to the emergence of a series of variants which expressed a high metastatic potential together with a high Gb3ose level. We also observed that Gb3ose was 10 times more prevalent on the cell surface in T3 cells than in a weakly metastatic clone. On the whole, these findings indicate that, in our system of metastatic cells, a high Gb3ose level correlates with metastatic phenotype. It is possible that the highly exposed Gb3ose in metastatic cells is relevant to the metastatic process in view of the role played by the unique molecular structure of this glycolipid in other models of cell-to-cell interaction. PMID- 2248639 TI - Modulation of neurogenic inflammation: novel approaches to inflammatory disease. AB - Neurogenic inflammation, which involves the release of neuropeptides from capsaicin-sensitive sensory nerves, may contribute to inflammatory diseases of the airways, joints, bladder, skin, eye and gut. Peter Barnes and colleagues review some of the therapeutic strategies that can be used to inhibit this neurogenic inflammation, with particular reference to the respiratory tract. PMID- 2248640 TI - Transfusion-associated graft-versus-host disease. PMID- 2248641 TI - Magnesium supplementation in pregnancy. PMID- 2248642 TI - Sapphire probes in obstetric laser surgery. PMID- 2248643 TI - Ritodrine infusion and cardiomyopathy. PMID- 2248644 TI - Ethics and routine ultrasonography in pregnancy. PMID- 2248645 TI - Spontaneous resolution of a nuchal fetal cystic hygroma diagnosed early in the second trimester of pregnancy. PMID- 2248646 TI - Thyroid dysfunction in postpartum depression. PMID- 2248647 TI - Colonoscopy or flexible proctosigmoidoscopy. PMID- 2248648 TI - Infantile colic treated by chiropractors: a prospective study of 316 cases. PMID- 2248649 TI - The effects of thiazides plus calcium channel blockers. PMID- 2248650 TI - Selection of subjects in community studies. PMID- 2248651 TI - Abnormalities in the brain and schizophrenia. PMID- 2248652 TI - Contraindications to immunisation. PMID- 2248653 TI - Asphyxia and cerebral palsy. PMID- 2248654 TI - Adaptation of a nebuhaler for use by infants. PMID- 2248655 TI - Treatment of acoustic tumors with radiotherapy. PMID- 2248656 TI - Torsional strength of the ankle in vitro. PMID- 2248657 TI - A new hypolipidaemic agent (gugulipid) PMID- 2248658 TI - Ultrasound measurement of femoral anteversion. PMID- 2248659 TI - Questions raised on efficacy of vitamin B-12 therapy for patients with dementia. PMID- 2248660 TI - If I have sex with a duck does that make me a drake? The Albion Street (AIDS) Centre, intravenous drug use and "prostitution". PMID- 2248661 TI - Low-tension glaucoma. PMID- 2248662 TI - The current state of lung transplantation. PMID- 2248663 TI - Vein graft permeability. PMID- 2248664 TI - The role of optic nerve sheath fenestration in management of anterior ischemic optic neuropathy. PMID- 2248665 TI - Interleukin-2 activity and serum levels of soluble interleukin-2 receptors in chronic active hepatitis B. PMID- 2248666 TI - Definition of primiparas. PMID- 2248667 TI - Fluid cooling of artificial sapphire tips of laser. PMID- 2248668 TI - Use of the T-ACE questions to detect risk-drinking. PMID- 2248669 TI - Caution in use of new test for ectopic pregnancy. PMID- 2248670 TI - Effects of ritodrine tocolysis on cardiac isozymes and electrocardiography. PMID- 2248671 TI - Critical comments on the treatment of tubal pregnancy with prostaglandins. PMID- 2248672 TI - Comments on bulimia. PMID- 2248673 TI - Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome. PMID- 2248674 TI - Chromosome 5 variation. PMID- 2248675 TI - NMR methods for measuring membrane transport rates. AB - NMR methods for measuring membrane transport rates rely in most cases upon there being a significant transmembrane difference in either the resonance frequency or the NMR relaxation times of the transported species. The first part of this review examines the various factors that can give rise to such differences in cell and vesicle suspensions. The second part provides an introduction to the theory of membrane transport measurements and describes the different ways in which transmembrane differences in NMR parameters have been exploited in monitoring both slow and fast membrane transport processes. PMID- 2248676 TI - Cervical cytology. PMID- 2248677 TI - Magnetic starch microspheres, biodistribution and biotransformation. A new organ specific contrast agent for magnetic resonance imaging. AB - The biodistribution and elimination of magnetic starch microspheres (MSM) were studied qualitatively and quantitatively by radioiron tracer studies and relaxation time measurements. One hour after injection of MSM (1 mg/kg of Fe), 85% +/- 5% of the dose was accumulated in the liver and 6.5% +/- 1.3% [corrected] in the spleen. The hepatic clearance led to 50% reduction in the T2 relaxation time of liver tissue. This T2 effect was halved after 24 hours and T2 reversed to baseline value within 5 days after injection. The radioiron was gradually cleared from the liver with a t1/2 of 4 to 5 days. Six weeks after injection of MSM, 72% +/- 7% of the radioiron dose was detected in the circulation in a nonsuperparamagnetic form associated with the erythrocytes. The results indicate a redistribution of iron from the liver and spleen via the erythroid bone marrow to the erythrocytes after injection of MSM. PMID- 2248678 TI - Appendectomy in Australian twins. PMID- 2248679 TI - When sympathectomy fails to relieve causalgic burning pain. PMID- 2248680 TI - Cisapride in Ogilvie's syndrome. PMID- 2248681 TI - Cell-specific activity of cis-acting regulatory elements in the promoter of the mouse multidrug resistance gene mdr1. AB - To define cis-acting elements implicated in transcriptional regulation of the mouse multidrug resistance gene mdr1, we have cloned and characterized the 5' end of the gene. Nucleotide sequence analysis identified TATA, GGGCGG, and CCAAT consensus sequence elements at positions -27, -47, and -83, respectively. The transcriptional activities of 5' deletion fragments from the promoter linked to a reporter gene were tested in mouse cell lines of different tissue origins shown to express different levels of endogenous mdr1 RNA. Sequences located between nucleotides -93 and +84 were able to confer basal promoter activity and cell specificity to the reporter gene. The addition to the basal promoter of sequences upstream of position -141 was found to up or down regulate the basal level of expression of the reporter gene in a cell-specific manner. PMID- 2248682 TI - The technique of polymerase chain reaction--a new diagnostic tool in microbiology and other scientific fields (review). AB - The polymerase chain reaction, a method of so far unknown sensitivity and specificity, is about to become an important diagnostic tool in microbiology. Practically even a single bacterium, virus particle, or parasite can be detected by it. Furthermore, this technique has been used with highly promising results in other scientific fields like genetics, forensic medicine and archeology. This article reviews technical aspects and variations of this new technique. PMID- 2248683 TI - Humoral antibody response of rabbits against experimental Serratia marcescens septicemia. AB - Rabbits reconvalescent from experimental septicemia due to serologically defined strains of Serratia marcescens were examined for the diversity of their humoral antibody response with traditional serological procedures and the Western blot (immunoblotting) technique. Trichloracetic acid (TCA)-whole cell extracts of the homologous and heterologous O-antigen reference strains served as the antigen for the latter procedure. Reconvalescent rabbit sera contained antibodies against the homologous lipopolysaccharide (LPS) moiety (molecular weight (MW) range = 45-31 kilodaltons (= k] and antibodies against numerous heat-modifiable, cross-reactive proteins, in particular 7 proteins characterized by MWs of 117 k, 95 k, 91 k, 71 k, 68 k, 38 k, and 33 k in TCA-whole cell extracts from the homologous as well as from 11 heterologous S. marcescens O-antigen reference strains. Rabbits, which had been actively immunized with TCA-whole cell extracts from representative S. marcescens strains, mounted a humoral antibody response remarkably similar to that of rabbits which had recovered from septicemia, except that the sera from the actively immunized animals interacted somewhat more strongly with an additional cross-reactive protein (MW = 47 k). Conversely, conventional anti-O and anti-H rabbit immune sera revealed antibodies directed predominantly against the homologous LPS moiety (MW range = greater than or equal to 200 k - less than or equal to 15 k). It was concluded that numerous proteinaceous cellular constituents of S. marcescens accounted for immunoblot cross-reactivity. PMID- 2248684 TI - In vitro cytotoxic effect of alpha-hemolytic Escherichia coli on human blood granulocytes. Inhibition by alpha-hemolysin antibody. AB - The influence of alpha-hemolysin antibody on the in vitro cytotoxic effect of alpha-hemolytic Escherichia coli bacteria and culture filtrates was investigated. Damage to human blood granulocytes was quantified by measuring the release of chromium 51 from labelled cells in the presence of whole or fractionated plasma containing alpha-hemolysin antibody. Anti-alpha-hemolysin activity was found exclusively in the IgG fraction of plasma. Human plasma contained "natural" alpha hemolysin antibody to various titers. Vaccination of rabbits resulted in only modest rises in alpha-hemolysin antibody titers. The cytotoxic effect of alpha hemolytic E. coli bacteria as well as that of bacterial culture filtrates was reduced in a titer-dependent way in the presence of plasma containing alpha hemolysin antibody. These results indicate that the cytotoxic effect of alpha hemolytic E. coli is inhibited by alpha-hemolysin antibody. PMID- 2248685 TI - Cefpodoxime: comparable evaluation with other orally available cephalosporins. With a note on the role of beta-lactamases. AB - The antibacterial activity of cefpodoxime, a new orally active methoxy-imino cephalosporin was evaluated in 470 recent isolates of gram-positive cocci and gram-negative rods from clinical specimens and compared to that of other orally active beta-lactam compounds. Cefpodoxime was highly active against ampicillin resistant enterobacteria producing the plasmid-mediated TEM-1, TEM-2 or OXA-1 enzymes, as was the case for the other newer compounds. However, it was poorly active against cefuroxime-resistant (MIC greater than or equal to 16 mg/l) E. coli isolates, thus resembling cefetamet and cefixime. It was inactive against isolates exhibiting a production of large amounts of class I beta-lactamase, as was the case with all other compounds studied. Cefpodoxime was highly active against beta-hemolytic streptococci and against Haemophilus influenzae, resembling the related agents. Moreover, its activity against Staphylococcus aureus was comparable to that of cefotaxime and exceeded that of cefetamet and cefixime. Cefpodoxime and the other methoxyimino cephalosporins exhibited a poor affinity to the plasmid-mediated TEM-2 and OXA-1 enzymes. The hydrolysis of cefpodoxime by class I beta-lactamases was barely detectable, whereas it served as a moderate substrate for the enzyme from Klebsiella oxytoca 3951. Cefpodoxime, cefetamet and cefixime were slowly inactivated by the enzyme from Proteus vulgaris 4917 (an enzyme with cefuroximase activity) and much poorer substrates than cefotaxime. PMID- 2248686 TI - Haemophilus aphrophilus isolated from blood. AB - H. aphrophilus was isolated from 11 successively cultivated blood samples of a male (72) with a fatal atypical endocarditis. Identification and differential diagnosis from Actinobacillus (Haemophilus) actinomycetemcomitans was done on the basis of phenotypic characters of the microorganism. PMID- 2248687 TI - Association of glucocorticoid receptors with prostate nuclear sites for androgen receptors and with androgen response elements. AB - Ventral prostate glands of intact normal rats contained low levels (2500 molecules/cell) of high-affinity (dissociation constant (Kd) 0.57 nmol/l) glucocorticoid receptors (GR). Levels of GR increased 2.8-fold 1 day after castration, and 4.3-fold 3 days after castration. Nuclear GR increased from a normal value of 1150 molecules/nucleus to 5200 molecules/nucleus 3 days after castration. The greater increase in intranuclear GR was in that associated with oligomeric chromatin. Although nuclear GR never approached the normal population of nuclear androgen receptors (AR; approximately 16000 molecules/nucleus), the selective rise in chromatin-associated receptors ensured that almost 60% of chromatin sites remained occupied. GR associated with prostate nuclear structures in a similar manner to AR, and exogenous GR bound saturably and with high affinity (Kd 100 pmol/l) to a similar number of sites as did AR. Both steroid receptors apparently competed for the same sites. In DNA-cellulose competition analyses, synthetic oligonucleotides containing glucocorticoid response elements or putative androgen response elements competed similarly against immobilized non specific DNA for both AR and GR. In view of these data and information from other sources, it is probable that the role of GR in the prostate should be assessed with a view to understanding its action under conditions of androgen deprivation. PMID- 2248688 TI - Production and utilization of monoclonal antibodies to human/rat corticotrophin releasing factor-41. AB - Murine monoclonal antibodies against human/rat corticotrophin-releasing factor-41 (CRF-41) were produced and characterized for use in the immunological and biological characterization of CRF-41. Spleen cells from BALB/c mice immunized with CRF-41 conjugated to bovine gamma-globulin were fused with a BALB/c-derived non-secretor X-63 myeloma line. Hybridomas were selected for CRF antibody production by enzyme-linked immunosorbent assay, and positive hybridomas cloned twice. Three monoclonal antibodies were obtained (KCHMB001, KCHMB002 and KCHMB003) and characterized as IgG1, IgG1 and IgG2a isotypes respectively, with affinity constants for rat CRF-41 of 30, 53 and 34 nmol/l respectively. All three monoclonal antibodies recognize an epitope contained between residues 34 and 41 of the human/rat sequence. The antibodies were able to neutralize the ACTH releasing activity of rat CRF-41, applied to rat pituitary fragments in vitro, in a dose-dependent manner. Isoelectric focusing showed that KCHMB003 detected bands of synthetic rat CRF-41 and rat [Met(O)21,38]-CRF-41 at pH 7.1 and 6.8 respectively. Use of KCHMB003 in a two-site enzyme-amplified immunoassay showed that this antibody recognizes both synthetic rat CRF-41 and immunoreactive CRF-41 in rat hypothalamic tissue extracts. PMID- 2248689 TI - Differential association of endogenous proenkephalin-derived peptides with membranes of microsomes from rat striatum, adrenal medulla and heart ventricle. AB - Proenkephalin-derived peptides, in common with other prohormones, are associated with membranes of microsomes and secretory granules in the bovine adrenal medulla. Post-translational processing of the precursor molecule varies depending upon the tissue. The relationship between post-translational events in different tissues was examined by studying the membrane association of endogenous proenkephalin-derived peptides in the crude microsomal fraction of rat adrenal medulla, brain striatum and heart ventricle. [Met]-Enkephalin and synenkephalin (proenkephalin(1-70)) immunoreactivities were quantified by radioimmunoassay after sequential enzymatic digestion with trypsin and carboxypeptidase B. Between 60 and 75% of total immunoreactive peptides present in intact microsomes of the three tissues were associated with membranes and specifically released with 2 M KSCN (pH 7.4). Analysis of the chromatographic profile of materials present in the soluble and associated fractions produced the following results. In the three tissues the materials associated with microsomal membranes corresponded to peptides larger than 3-5 kDa and displayed synenkephalin and [Met]-enkephalin immunoreactivity. Adrenal and heart microsomes showed a continuous pattern of membrane-associated proenkephalin-derived peptides of high, intermediate and low molecular weights containing the synenkephalin and [Met]-enkephalin sequences. These tissues, however, presented quantitative differences, as the highest concentrations belonged to materials larger and smaller than 12.5 kDa in adrenal and heart microsomes respectively. On the other hand, brain striatal microsomes displayed a discontinuous pattern of associated materials, with the absence of some products of high and intermediate molecular weight. Only in the soluble fraction of striatal microsomes were peptides detected of high and intermediate molecular weight containing the [Met]-enkephalin but not the synenkephalin sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248691 TI - Is anonymous peer review the best way to review and accept manuscripts? PMID- 2248690 TI - Family Spirosomaceae: gram-negative ring-forming aerobic bacteria. AB - The bacteria having a unique ring-like morphology first isolated from nasal mucus by Weibel in 1887 were classified as a new genus Spirosoma by Migula in 1894. However, because these bacteria were not completely described for taxonomic purposes and their cultures were no longer available, the genus was deleted from the Bergey's Manual of Determinative Bacteriology, 6th edition, 1948. Orskov (1928) created a new genus "Microcyclus" (a name that has been found to be illegitimate and replaced with Ancylobacter by Raj 1983) to describe these nonmotile vibroid bacteria that occasionally formed ring-like structures. Several similar isolates found in many countries during the last 60 years were readily identified with this genus on the basis of the characteristic morphology alone. For the first time, these fascinating bacteria were extensively reviewed by Raj in 1977 and again in 1981. However, during the last decade, the systematics of these microcyclus bacteria has been reexamined and redefined. It has been shown that these Gram-negative ring-forming aerobic bacteria constitute a heterogeneous group of five genera: Ancylobacter, Cyclobacterium, Flectobacillus, Runella, and Spirosoma; the last four genera have been grouped into a family Spirosomaceace (reviving the old discarded name originally proposed by Migula 1894), thus separating them from the genus Ancylobacter which remains unaffiliated with any family yet (Bergey's Manual of Systematic Bacteriology, Vol. I, 9th ed., 1984). Also, this article reviews the recent studies reported on the ecology, morphogenesis, metabolism, and physiology of the picturesque bacteria. PMID- 2248692 TI - Blood magnesium status of patients with parathyroid disease. AB - The blood magnesium status--plasma and red blood cell (RBC) concentration and mononuclear blood cell (MBC) content of magnesium and parathyroid hormone (PTH) were determined in 6 patients with chronic hypoparathyroidism and 9 patients with primary hyperparathyroidism before and after surgical cure of the disease. The magnesium content of MBCs and concentration of RBCs increased significantly (p less than 0.01) after the surgical correction of primary hyperparathyroidism. Patients with chronic hypoparathyroidism had significant increase (p less than 0.05) of magnesium in RBCs and MBCs compared with the control group. No significant difference was observed for the plasma magnesium concentration for hypoparathyroid patients compared with the control group and hyperparathyroid patients before and after surgical care. These results suggest that endogenous PTH affects the concentration of magnesium in RBCs and magnesium content in MBCs but does not alter significantly the concentration of magnesium in plasma. PMID- 2248693 TI - Unusual observations on hypermagnesemic levels and cardiorespiratory effects in neonatal swine. AB - Mg is being used as a therapeutic agent in different clinical conditions, i.e. preeclampsia or eclampsia, and as a tocolytic agent to prevent premature delivery. For these reasons we decided to systematically investigate the cardiovascular and respiratory effects of excess Mg in 25 piglets less than 1 day to 3 months of age, lightly anesthetized with Saffan, tracheotomized, paralyzed with C-10 and artificially ventilated on 100% O2. A 1.0 M infusion of MgCl2 was given for 15-60 min, and arterial plasma samples were drawn before and at the end of the infusion for the determination of plasma Mg and Ca levels. Phrenic nerve activity was recorded monophasically simultaneously with arterial blood pressure, electrocardiogram, end-tidal CO2 and intratracheal pressure on a dynograph and on analog tape. In a subset of experiments (n = 6), spontaneous ventilation was monitored in piglets of different ages to determine the Mg concentration at which spontaneous ventilation ceased. Blood gases were measured at 45-min intervals, as well as both immediately before and after the MgCl2 infusion, and pCO2 and pH were maintained within normal limits. As a consequence of the high plasma concentration of Mg, mean arterial pressure and heart rate declined, and the inspiratory duration significantly decreased. Our results indicate that young piglets can survive high levels of plasma Mg (greater than 14 mM). PMID- 2248694 TI - Continuous intravenous infusion of magnesium sulfate after acute myocardial infarction. AB - Two hundred and fifty patients admitted with acute myocardial infarction were treated with a continuous infusion of magnesium sulfate for 24 h (a total of 46 mmol of elemental magnesium). Only 1 patient had ventricular fibrillation; no patient had sustained ventricular tachycardia requiring cardioversion. Twenty five patients had short runs of non-sustained ventricular tachycardia and did not need cardioversion. In 6 further patients, the infusion had to be discontinued because of a drop in blood pressure. The in-hospital mortality for the group was 3.4%. PMID- 2248695 TI - Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. AB - Magnesium may be important in the pathogenesis of coronary heart disease and sudden death. To study the role of magnesium, 400 high risk individuals were asked to volunteer either for a magnesium-rich diet (group A, 206) or for our usual diet (group B, 194) for 10 years in a randomized fashion. The age groups were between 25 and 63 years and the majority (374) of them were males. At entry to the study, age, sex, incidence of hypertension, diabetes, hypercholesterolemia, smoking, coronary disease and diuretic therapy were comparable. Dietary magnesium intake in group A (1,142 +/- 233 mg/day) was higher than in group B (418 +/- 105 mg/day). Total complications in group A (59; 28.6%) were significantly (p less than 0.001) less compared to group B (117; 60.3%). Sudden deaths were one and a half times more common in group B than in group A. Total mortality in group A (22; 10.7%) was significantly (p less than 0.01) less than in group B (34; 18.0%). A greater number of complications and increased mortality in group B subjects was consistent with a higher incidence of hypokalemia, hypomagnesemia and coronary risk factors in group B patients. Mean serum magnesium levels in group B participants were significantly (p less than 0.01) lowered compared to the mean magnesium level in group A participants who were administered the magnesium-rich diet. It is possible that increased intake of dietary magnesium in association with the general effects of a nutritious diet can offer protection against cardiovascular deaths among high-risk individuals predisposed to coronary heart disease. PMID- 2248696 TI - Magnesium and intracellular sodium activity in cardiac Purkinje fibers. AB - The actions of magnesium on intracellular sodium activity (aiNa), transmembrane potentials and contractile force were studied in sheep cardiac Purkinje fibers perfused in vitro. Increasing [Mg]o from 1.05 to 2-8 mM shortens the action potential, decreases force and increases aiNa in active (and quiescent) fibers. High Ca (8.1 mM) increases force and decreases aiNa: in its presence, 8 mM Mg ('high Mg') decreases force as well as the action potential duration and still increases aiNa. Manganese decreases force and aiNa: the effects of high Mg are not changed by Mn-induced blockade of the slow channel. Even in the presence of 0.25 mM lidocaine (which decreases action potential duration, force and aiNa), high Mg increases aiNa, has little effect on the action potential duration and increases the threshold requirements. In the absence of [Ca]o, 1.35 mM Sr increases the action potential duration as well as aiNa and reduces force: high Mg markedly decreases aiNa, force and action potential duration. Thus, Mg decreases the duration of the action potential (as Ca does) but (in contrast to Ca) decreases contractile force (possibly by acting on intracellular structures) and increases intracellular Na activity. These effects are not dependent on Ca or Na influx and show that the increase in aiNa by Mg is the net result of opposing actions. PMID- 2248698 TI - The anophthalmic socket. PMID- 2248697 TI - Ancient and contemporary history of artificial eyes. AB - Throughout history, the human eye has been mentioned by authors as the most precious of gifts. It unveils the entire outer world to our consciousness, gives life expression and dignity to the face. The loss of an eye must therefore have always been regarded as the greatest misfortune. The ancient cultures of Babylon, Jericho, and Egypt used "art-eyes" in mummies, sarcophagus lids, and statues; they were made from precious stones, silver, gold, and copper as a symbol of light and life in their religious beliefs. Most of the recorded sources concerning the ancient practice of medicine were among the scrolls contained in the library of Alexandria. In the period between the Roman Colonial wars, the rise of Christianity and the fall of Alexandria to Arabs in 642 A.D., almost all of these sources, including those concerning the practice of Ophthalmology were lost. The largest collection of antiquity "art-eyes" and artificial eyes, mentioned in this paper, are found in the collection of the firm of Mueller and Sohne, Wiesbaden, Germany. They include the progress made in human artificial eyes to modern times. Historically, man has tried to alleviate the psychological suffering incurred by the loss of an eye, by hiding or covering the defacement with a patch. Of greater significance are the efforts made by the ophthalmologist and the ocularist (past and present) to restore functionally and cosmetically the natural facial appearance by means of an ocular prosthesis that corresponds to the remaining natural eye. Associated problems frequently concern both the reconstructive surgeon, who must be informed of the ocular prosthetic possibilities that are within the capacity of the ocularist, and the ocularist, who must create the prosthesis. PMID- 2248699 TI - Diagnosis and treatment of complications of enucleation and orbital implant surgery. AB - Careful surgical technique is important in enucleation surgery. Gentle and careful handling of tissues leads to superior cosmetic results and fewer complications. Extrusion of orbital implants may occur early or late. Small extrusions may be treated with a scleral patch, and larger extrusions with an acrylic sphere wrapped in fascia lata or donor sclera. Dermis fat grafts are also satisfactory secondary implants. PMID- 2248700 TI - A history of facial and ocular prosthetics. AB - This article traces the history of facial and ocular prosthetics. Creative individuals who have made significant contributions are highlighted and the evolution of techniques and materials is presented. In view of the significance placed upon facial beauty in today's society, it becomes incumbent upon us to recognize the ingenuity and skill of those in the past to gain appreciation for the present state of the art and to provide incentive for improving facial and ocular prosthetic restorations in the future. PMID- 2248701 TI - Empirical impression technique for artificial eye fitting. AB - Using an impression of the anophthalmic socket to facilitate the design of an artificial eye is common practice today. The Modified Impression technique was described in the American Journal of Ophthalmology, February 1969, by Lee Allen and Howard E. Webster. It is a highly successful method that involves taking an impression of the socket using an impression tray, then making a wax casting of the impression, and final modifications to the anterior aspect of the wax model. A different technique has been in use in our office and elsewhere for more than 15 years, also with a high degree of success. We've dubbed it the "Empirical/Impression" method. It involves similar steps to the Modified Impression system, but in different order: first a wax model of the anterior aspect of the eye is designed and modified; second, an impression is made of the socket, using this wax model as an impression tray. The primary advantage of this method is efficiency. It involves one less laboratory procedure, hence making a "one-day custom eye" a reality. Although this process can be used in almost any case, the Modified Impression technique may work better for certain highly irregular sockets where "reading" the fornices by empirical means may be difficult. Either method requires a highly skilled and experienced fitter to make appropriate modifications to the anterior aspect of the prosthesis. PMID- 2248702 TI - Fitting the anophthalmic socket: achieving cosmesis with comfort. AB - In attempting to achieve acceptable cosmesis while maintaining comfort for the anophthalmic patient, communication between the ocularist and oculoplastic surgeon is of paramount importance. The ocularist must realize his limitations in correcting deformities prosthetically and must communicate these limitations to the ophthalmologist when surgical alternatives are being considered. PMID- 2248703 TI - Fitting a prosthesis over phthisis bulbi or discolored blind eyes. AB - An ocular prosthesis fitted over phthisis bulbi or a discolored blind eye of near normal size is a positive approach to improve the cosmetic appearance and psychological well-being of the patient. Unless surgical intervention is essential, fitting a prosthesis over the residual eye is a successful alternative to enucleation or evisceration. In general, for these individuals there is minimal disruption of the periocular tissues, thus, reducing fitting problems associated with enucleation and evisceration. A prosthesis properly fitted over phthisis bulbi or a discolored blind eye will maintain the integrity of the orbital anatomy, enhance cosmesis, and accelerate the rehabilitation of the patient. PMID- 2248704 TI - Care of the ocular prosthesis. AB - The goal of the ocular prosthetic procedure is to return the patient to a normal appearance and lifestyle. Modern eye prostheses can give the patient an excellent physical and cosmetic result. In the final analysis, the success or failure of the long-term use of the prosthesis is dependent on the cooperation of the patient in the care of his ocular prosthesis. It is important for the patient to be aware of and proficient in the care of his prosthesis. Patient education and professional follow-up will ensure the best prosthetic fit, appearance, and health of the anophthalmic socket. PMID- 2248705 TI - Enucleation with placement of fat graft in Tenon's capsule. 1901. PMID- 2248706 TI - Enucleation of the eye with implantation of the patient's fat into the cavity. 1917. PMID- 2248707 TI - Use of autogenous materials in reconstructing the anophthalmic socket. AB - A variety of autogenous materials may be used for orbital implantation in the anophthalmic socket. An understanding of the pathology of the socket is necessary to treat the problem correctly. Autogenous grafts have been used successfully to treat the superior sulcus deformity, extruding implant, and the contracting socket. The major advantages of autogenous material are its minimal inflammatory reaction and its total compatibility with the host. PMID- 2248708 TI - Complications of dermis-fat orbital implantation. AB - Primary dermis-fat implantation can be effectively performed in cases without pre existing systemic vascular disease or orbital burns. Meticulous handling of the graft (using a Goeller trephine and Tenon's capsule traction sutures), filleting Tenon's capsule, and avoiding cautery of the graft bed may minimize graft necrosis and atrophy. Pyogenic granulomas of the conjunctival-graft interface and graft hirsutism are easily managed. Keratinization of the socket, graft wound dehiscence, donor site hematomas, and wound dehiscence are avoided with careful surgical technique. Secondary dermis-fat orbital implantation may add orbital volume and conserve the conjunctival fornices, but may also suffer a slightly increased frequency and amount of graft absorption. PMID- 2248709 TI - Prosthesis fitting following autogenous dermis-fat orbital implantation: an ocularist's view. PMID- 2248710 TI - Prosthetic reduction of upper eyelid ptosis. AB - It is important that an ocularist be knowledgeable of the five types of anophthalmic ptosis, their causes and most effective treatment method. In earlier days ocularists had only one method of correcting this problem. With the advent of plastic material several more were invented, but none were totally effective or comfortable for the patient. This chapter describes the five types of ptoses, some simpler methods for correction with prostheses, but emphasizes a complex method initiated in the early 1950s by Lee Allen. It has been used by many other ocularists since. A description of the method and its effectiveness is discussed. PMID- 2248711 TI - Reconstruction of the anophthalmic socket: lower eyelid malposition and canthal tendon laxity. AB - There are a number of etiologies underlying the development of socket deformity with associated lower eyelid malposition, lateral canthal tendon laxity, and/or contraction of the inferior fornix. In addition to cosmetic considerations, each of these anatomic problems can interfere with comfortable wear and retention of a prosthesis. This chapter gives an overview of these problems and details our preferred surgical approaches to repair of these anatomic deformities. Specifically discussed are techniques for: mucous membrane and ear cartilage grafting to repair lower lid inner lamellar tissue shortage, reconstruction of the inferior fornix/cul-de-sac, direct lower eyelid lateral canthal resuspension, and resuspension using a periosteal flap or autogenous fascia lata from the iliotibial tract. PMID- 2248712 TI - Correction of superior sulcus defects after enucleation. AB - Anophthalmic patients can develop a deep recess or sulcus in the upper lid, usually associated with enophthalmos. If due to an absence or loss of a socket implant, a secondary one can be implanted. In those cases with a socket implant, one method of treatment is directed at adding a silicone block to the inferior orbit to cause a forward movement of fat to fill out the upper eyelid as well as reducing the enophthalmos. Another approach, particularly if enophthalmos is minimal, is to directly implant a dermis-fat graft into the upper eyelid. The graft is taken from above the iliac crest and the amount implanted should create a slight overcorrection, allowing for some fat absorption. PMID- 2248713 TI - Uses of RTV silicone in orbital reconstruction. 1977. PMID- 2248714 TI - Subperiosteal volume augmentation of the anophthalmic socket with RTV silastic. AB - Patients who have worn an ocular prosthesis for many years often develop laxity of the lower eyelid and deepening of the superior sulcus caused by downward displacement of the orbital contents. Herein we describe our technique and results with the lateral canthal sling and subperiosteal room temperature vulcanizing (RTV) silastic volume augmentation procedure performed through a single incision in the lateral canthus. PMID- 2248715 TI - Correcting superior sulcus deformities. AB - There are many different procedures to camouflage the superior sulcus deformity that occurs after an evisceration or enucleation. We have studied 5000 anophthalmic patients. In every case the previous adaptation of the prosthesis was satisfactory. We noted the frequency of the superior sulcus deformity, and we would like to discuss silicone oil infiltration and a modified polymethyl methacrylate (PMMA) banana superior sulcus implant. The silicone oil infiltration is easily performed and the results are permanent. PMID- 2248716 TI - Abnormalities of the palpebral aperture. AB - The socket surfaces, conjunctival fornices and palpebral aperture are intimately related. Any socket or fornix abnormality will affect the contour and size of the palpebral aperture. Conversely, a cicatricial lid deformity will alter the depth and contour of the conjunctival fornix. Any surgical correction of a lid malposition must calculate the resultant effect on the socket. PMID- 2248717 TI - Plastic artificial eyes: overview and technique. AB - Eye prosthetics and its practitioners have evolved through self-development studies, to become an integral part of the ophthalmic plastic surgery multidisciplinary team. Eye prosthetics is a distinct art and science in dealing with the many facets of eye surgery. The ocularist must have in his armamentarium alternate procedures, flexibility, cooperation, and become knowledgeable of all the options available to him. This in turn will offer opportunities for providing the plastic artificial eye patients with the best final results possible. PMID- 2248718 TI - Enucleation and psychic trauma. AB - The surgeon must be aware of the psychological impact on a patient when performing an enucleation. The surgeon should offer patients psychiatric assistance to deal with the trauma of an enucleation. The formation of a group therapeutic organization may be a viable approach to gathering patients to talk about their concerns. "Enucleations Anonymous" is proposed. PMID- 2248719 TI - Psychological recuperation of the patient. AB - This seldom discussed subject is brought into focus with examples of the complex emotional ramifications of eye loss. The professional who is best equipped to counsel these patients is the ocularist. Patients psychological needs are successfully met with accurate information. Our objective is to alter the patient's attitude concerning losing an eye. A step-by-step method of achieving that goal is presented. PMID- 2248720 TI - Surgical psycho-ophthalmology and contracted sockets. AB - Surgical psycho-ophthalmology is the integration of ophthalmic surgery and medicine with basics in psychiatry and psychology, lest the psyche be forgotten amid the spectacular leaps in techniques and technology, or our judgment be veiled by our related psychodynamics [1]. Its scope encompasses a much broader spectrum than the conventional psychosomatic eye diseases. Besides due consideration of the psychological and physical conditions of patients, it increases the awareness of the surgeons' psychodynamics that reflect on our continuing judgment before, during, and after surgery. Further, surgical psycho ophthalmology impacts on the indications, timing, planning, and performance of each individual operation and/or reoperation. It equally emphasizes both the psychologic priming of patients and attuning of the surgical team. In establishing and maintaining rapport with the patient, surgical psycho ophthalmology helps to curb the growing problems of malpractice, iatrogenicity, and noncompliance. It also stresses careful weighing of the risk/benefit ratio in adherence to the surgical axiom: "primum non nocere". Despite all advances and ingenuity in contracted socket surgery, the challenge still remains. However, with the proper evaluation and management in the perspective of psycho ophthalmology we may achieve success, not only in esthetics, but also in sight preservation, and even in life salvage. PMID- 2248721 TI - Mobility implants: a review. AB - We present a brief review of mobility implants, their contribution, and the experiences derived after almost 40 years since the new concepts of full mobility implants were introduced. In early 1940, experiments with a new material for the making of plastic artificial eyes was also being considered for the making of orbital implants. Methyl-methacrylate (MMA) had proven inert and satisfactory for dental products. The Surgeon Generals office of the Armed Services encouraged further research and experimental work in the development of plastic eyes. The success of the new material sponsored the beginning of great expansion with new concepts for orbital implants. Through a period of more than a decade, the design and types of implants went through three stages. First, the buried implant was introduced, then the exposed integrated followed, and the buried integrated subsequently followed. The path of progress was not smooth. Theoretically correct designs and surgical procedures met unexpected practical difficulties for the ophthalmic surgeon, the patient, and the eye maker. Surgical and technical efforts were carefully reviewed to eliminate the problems encountered, only to have further unforeseen complications arise. Infections, extrusions, and migration of the implant were not uncommon. The exposed integrated implant was eventually abandoned. However, there were some extraordinary successes of mobility. A new era introduced fully buried mobility implants that were more successful. However, this procedure also produced some problems, causing infection (or allergy), extrusion, and migration. Tantalum mesh and gauze gave great promise with the inception of their use. Orbital tissue grew into the material in an astonishing way, making it possible to secure the extraocular muscles and tenons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248722 TI - The role of the ocularist. AB - The ocularist plays a significant role in the rehabilitation of patients suffering the loss of an eye. As with any role, the function of the ocularist is a multidisciplinary one, involving a wide range of services in the overall management of the patient. PMID- 2248723 TI - The team approach to the anophthalmic patient. AB - Close interaction between the patient, surgeon, and ocularist is necessary to obtain the most ideal prosthesis. Communication between these parties will facilitate the patient's adjustment to the anophthalmic state and the maintenance of a healthy anophthalmic socket. PMID- 2248724 TI - Orbital anatomy for rehabilitation: the ocularist's point of view. AB - In the post enucleation and evisceration patient, we must continually seek to resolve the functional and cosmetic defects that occur following surgery. Fitting a prosthesis that appears to be symmetrical with the fellow eye is the measuring stick of our success. The success or failure in achieving this cosmetic symmetry will determine to a great degree the rehabilitation of the patient. It is important for the ocularist to have at least a basic understanding of the anatomic changes that have resulted in the anophthalmic socket to correctly assess and treat these changes. The authors suggest a method detailing the steps involved in making an accurate clinical assessment of the patient. The authors will also outline the defects normally associated with post enucleation syndrome, their usual causative effects, and provide a suggested reading list supplying information on both surgical and prosthetic correction for each of these areas. PMID- 2248725 TI - Evisceration of the globe with artificial vitreous. 1884-1895. PMID- 2248726 TI - Modified enucleation. AB - Standard enucleation techniques provide excellent results. Modifications can render the operative field bloodless and permit the performance of all manipulations under direct visualization. Standard enucleation has been postulated to disseminate choroidal malignant melanoma cells as a result of fluctuations in intraocular pressure incident to surgical manipulations. It is possible that the stabilization of intraocular pressure preceding induction of tumor freezing may decrease such dissemination and thereby increase survival. PMID- 2248727 TI - Use of GORE-TEX (polytetrafluoroethylene) in the anophthalmic socket. AB - The GORE-TEX soft tissue patch is composed of large open spaces surrounded by polytetrafluoroethylene (PTFE) fibers connected to nodules of solid PTFE. It was used in 12 oculoplastic surgery patients. Primary and secondary spherical silicone implants were wrapped with a GORE-TEX patch and implanted into Tenon's capsule. This study reports our first results using this versatile material. PMID- 2248728 TI - The universal orbital implant: indications and methods. AB - Major criticisms of quasi-integrated implants, such as the Iowa Implant, have been the time-consuming surgical technique needed to implant the prosthesis, and the high rate of extrusion. The Universal Implant (Oculo-Plastik, Montreal) is designed with these concerns in mind. In addition, those qualities that produce the motility advantages of a quasi-integrated implant and the ease of placement of a sphere have been incorporated into the design of the Universal Implant. The Universal Implant also (1) uses a faster implantation technique at surgery, (2) avoids cleaning the muscles, (3) has smaller mounds that are lower and more rounded, and should decrease the late extrusion rate, (4) can be used as an evisceration implant, enucleation implant, or secondary implant, and (5) has a larger girth and radius on the posterior surface that, in turn, helps support orbital fat and tissues and results in a more natural superior sulcus. It is recommended that the Universal Implant be used by surgeons who were pleased with the Iowa Implant, as the Universal implant represents an excellent alternative with major advantages over most other enucleation implants. PMID- 2248729 TI - Solvent model for protein crystals: on occupancy parameters for discrete solvent sites and the solvent continuum. AB - On the basis of test calculations, Kundrot & Richards [Acta Cryst. (1987), B43, 544-547] suggest that for models of protein crystal structures based on limited resolution X-ray data, it is not appropriate to vary both the occupany (Q) and thermal (B) parameters for the solvent molecules during refinement. There are compelling reasons, however, to adjust both parameters. If the data are sufficiently extensive to include a B parameter for each solvent site, then an adjustable Q parameter should also be included if the model is to represent physical reality. To fix Q at some arbitrary value as suggested, means that differences in occupancy will be absorbed in the 'thermal' parameters, leading to the errors corresponding to the electron density plots of Kundrot & Richards. Although the errors appear to be relatively small, they will be accentuated in Fourier maps of complex structures based on real data, causing error peaks, both positive and negative, that may greatly exceed the random errors. The current practice of using the scattering factor of the O atom, fO, for the water molecule neglects the scattering from the H atoms. A modified scattering factor based on fO- would approximate the scattering from water molecules better. Finally, the solvent continuum should be included in the model, and the low-order data included in calculating the Fourier maps from which the Q parameters are estimated. PMID- 2248730 TI - Effect of the anisotropy of anomalous scattering on the MAD phasing method. AB - The analysis of X-ray diffraction intensities is complicated by the anisotropy of anomalous scattering (AAS) that can occur due to resonance associated with transitions between core electrons and valence molecular orbitals. Substantial AAS has been observed directly in diffraction data near the K edge of selenium in selenolanthionine [Templeton & Templeton (1988). Acta Cryst. A44, 1045-1051] and in pleiochroism of X-ray absorption in selenobiotinyl streptavidin [Hendrickson, Pahler, Smith, Satow, Merritt & Phizackerley (1989). Proc. Natl Acad. Sci. USA, 86, 2190-2194]. The impact of AAS on the multiple-wavelength anomalous diffraction (MAD) method for phase determination is of particular interest in the context of this chemical state of selenium in the light of a general method that has been developed to incorporate selenomethionine into proteins for use in MAD phasing [Hendrickson, Horton & LeMaster (1990). EMBO J. 9, 1665-1672]. The first step of the MAD phasing method necessarily assumes that the anomalous-scattering factors are isotropic and our first aim here is to evaluate the effect of this approximation on initially determined phases. To obtain ultimate phases free from the effects of anisotropy, a least-squares procedure has been written in which global parameters (i.e. pertaining to the whole data set) are refined simultaneously with local parameters (i.e. pertaining to a given node h). The AAS is taken explicityly into account by considering f' and f" as tensors instead of scalars [Templeton & Templeton (1982). Acta Cryst. A38, 62-67], and the components of the f' and f" tensors are among the refinable global parameters. The effectiveness of this procedure is tested with data simulated from the refined atomic model of selenobiotinyl streptavidin. The application of this procedure to actual Photon Factory measurements is also described. The results show that AAS does not cripple the MAD method, and that phases uncorrupted by these effects can be recovered. PMID- 2248731 TI - Differential effect of aging on 3H-SCH 23390 binding sites in the retina and in distinct areas of the rat brain. AB - The effects of age on the binding parameters of the selective D-1 dopamine (DA) receptor antagonist 3H-SCH 23390 were studied in membrane preparations from rat striatum, substantia nigra, olfactory tubercle, prefrontal cortex and retina. When compared with 3-month-old animals, there was a significant decrease in the density of 3H-SCH 23390 binding sites in the striatum (-25%), substantia nigra ( 24%), and olfactory tubercle (-23%), but not in the prefrontal cortex of senescent (23-month-old) rats. The affinity of 3H-SCH 23390 for D-1 DA receptors did not change with age in any of the brain areas analyzed. In contrast, the density of 3H-SCH 23390 binding sites was higher (+53%) in the retina of aged rats that in 3-month-old controls. Confirming previous studies, we observed that light deprivation induced a significant increment in the density of 3H-SCH 23390 binding sites in the retina of adult rats (+31%) but not in the retina of aged animals. The ability of light exposure to activate DAergic neurons in the rat retina was not altered by normal aging. In fact, a similar increase in the concentration of DOPAC was observed in the retina of light-adapted adult and senescent rats when compared to their respective dark-adapted controls (+94% and +95%, respectively). The results indicate that aging has a differential effect on D-1 DA receptors in the retina and different areas of the rat brain. Finally, the age-related increment in the density of retinal D-1 DA receptors does not appear to depend on presynaptic mechanisms, since DA metabolism is increased by light to the same extent in young and aged rats. PMID- 2248732 TI - 3,4-Dihydroxyphenylacetic acid (DOPAC) as an index of noradrenaline turnover: effects of Hydergine and vincamine. AB - Among the drugs commonly used in the treatment of memory disorders of the elderly, vincamine and hydergine have been shown to moderately increase the firing rate of noradrenergic locus coeruleus (LC) neurons. Since changes in electrical activity of noradrenergic neurons are generally reflected in corresponding alterations of the turnover of this transmitter, the effects of these drugs on the accumulation of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) in the presence and absence of the dopamine-beta-hydroxylase inhibitor, FLA 63, were studied in the LC as well as in two of its projection areas, the hippocampus and the cerebellum. Characterization of this procedure with the alpha 2-adrenoceptor antagonist, idazoxan, the corresponding agonist, clonidine, the alpha 1-adrenoceptor antagonist prazosine, and haloperidol, suggested that--DOPAC changes are more suitable than those of DA or DOPAC/DA ratios in reflecting changes in noradrenaline (NA) turnover, inhibiting DBH is advantageous if NA turnover is to be measured in projection areas, but not in LC, and haloperidol and prazosine, in principle, did not affect NA turnover. Vincamine and hydergine at 10 mg/kg doses, at which they were reported to increase LC firing by 50%, did not induce a change in NA turnover in any of the areas. This, together with the data obtained with haloperidol, suggests that a minimal increase in the firing rate of LC cells (+140%) is required before it could influence the turnover of NA, as measured by DOPAC changes. Thus, the stimulating effect of nootropics on the central noradrenergic system may be more sensitively detected by electrophysiological techniques than by biochemical ones. PMID- 2248733 TI - Evidence that cholinergic receptors of muscarinic type may modulate vasopressin release induced by metoclopramide. AB - Studies were carried out in the rat in order to investigate whether cholinergic mechanisms may be involved in vasopressin (VP) release induced by metoclopramide (MCP). The intravenous injection of MCP induced dose-related increases in plasma VP levels in water-loaded rats. These effects were prevented by atropine sulphate, but not by pirenzepine hydrochloride indicating that activation of cholinergic receptors of M-2 type was possibly required for the biologic response. PMID- 2248734 TI - Why pediatric otolaryngology? PMID- 2248735 TI - Surgical strategy in thyroid disease. AB - Over the past 8 years, 311 patients have undergone surgical treatment by the senior authors for thyroid disease. Over 80% of the cases were performed by the head and neck surgical service at Olive View County Hospital, Sylmar, Calif, with the remainder performed at UCLA-affiliated institutions. This service is an important source of thyroid surgical training for UCLA head and neck residents who rotate through this major affiliate. The purpose of this communication is to review our experience with these cases; to describe our overall surgical strategy; and to detail the specifics of our surgical procedure, which we have developed to safely train residents in the treatment of these challenging cases. This article deals with the specific problems of preservation of the recurrent nerve, the parathyroid glands, and the techniques for reimplantation of injured parathyroid glands; the management of larger, substernal thyroid glands; and our techniques for partial thyroid surgery. In addition, the difficult decisions in the management of thyroid cancer, such as completion thyroidectomy; the management of lymph node mestastases; and how tracheal, esophageal, or laryngeal invasion should be managed are discussed. An initial section describing the general preoperative examination of these patients is also included, so that the proper surgical strategy can be developed prior to entering the operating room. PMID- 2248736 TI - Carotid body tumors. AB - The surgical management of carotid body tumors requires identification and preservation of neural and vascular structures without compromising resection of the neoplasm. Fifteen patients were examined and treated for carotid body tumors at the Cleveland (Ohio) Clinic Foundation from 1979 through 1987. The benchmark of diagnosis is bilateral carotid angiography. When neural structures are free of tumor, meticulous dissection facilitates their preservation. Large tumor size increases risk for arterial resection necessitating reconstruction. The use of a vascular shunt minimizes the risk of cerebral ischemia. Postoperative intravenous digital subtraction angiography allows for evaluation of arterial repair. A retrospective review of 15 carotid body tumor resections performed in 14 patients revealed no evidence of tumor recurrence, no mortality associated with surgical intervention, no postoperative cerebrovascular accident, and limited morbidity associated with unavoidable sacrifice of neural elements. PMID- 2248737 TI - Unknown primary squamous cell carcinoma metastatic to the neck. AB - We analyzed retrospectively 157 cases of metastatic neck squamous cell carcinoma from unknown primary sites, treated with surgery, radiotherapy, excisional biopsy, and combined modalities. Median follow-up was 74 months, and overall actuarial survival was 55% at 5 years. The surgery-treated group, despite a higher rate of manifesting primary tumors, had significantly better survival at 5 years compared with those receiving radiation therapy, of whom 23% had residual disease after treatment. Primary tumors were discovered during follow-up in 16% overall. Different treatments yielded comparable results in lower-staged neck disease (NX, N1, N2a), while surgery appeared more effective in controlling advanced disease (N2b, N3a). Factors that affected survival include neck stage, connective tissue invasion, and presence of recurrent or residual disease after treatment. PMID- 2248738 TI - Oncogene amplification in squamous cell carcinoma of the head and neck. AB - Cellular oncogenes appear to be involved in the control of normal cell growth and differentiation. The abnormal activation of these genes in naturally occurring and experimentally induced cancers may have an important role in the expression of the malignant phenotype in cancer cells. Mechanisms for the activation of these genes include chromosomal translocation, point mutation, and DNA amplification. The amplification of specific oncogenes correlates with clinical prognosis in several human malignancies, including breast cancer and neuroblastoma. We examined 21 fresh-frozen human squamous cell carcinomas of the aerodigestive tract for amplification of 10 known cellular oncogenes (c-myc, N myc, L-myc, N-ras, H-ras, K-ras, erb-B, erb-B2, raf, and int-2), using Southern blotting techniques. Eleven of 21 tumors demonstrated a two-fold to 11-fold amplification of the int-2 oncogene, one member of a family of genes related to basic fibroblast growth factor. Amplification of c-myc, a gene that codes for a DNA-binding protein involved in the regulation of cell growth, was seen in two tumors. None of the other eight genes studied were amplified in any of the tumor specimens. PMID- 2248739 TI - Simultaneous 'dual system' rehabilitation in the treatment of facial paralysis. AB - Simultaneous dual system rehabilitation of facial paralysis involves using two independent reanimation techniques to optimize facial movement in both a quantitative and qualitative manner. These techniques involve the use of nerve grafting or crossover procedures combined with a dynamic muscle transfer. A group of 37 patients who underwent five different combinations of reanimation was analyzed. The techniques were evaluated using a standard rating scheme for judging success of reanimation procedures. The combination of a masseter muscle transfer to the lower region of the face and a cable graft of the upper facial nerve division appeared to offer excellent results in terms of independent motion of the upper and lower regions of the face and good eye closure, while allowing spontaneous mimetic function in 50% of cases. The advantages and disadvantages of the other techniques are described. The clinical situations in which these techniques have advantage over single reanimation techniques are outlined. PMID- 2248740 TI - The efficacy of oral steroids in the treatment of persistent otitis media with effusion. AB - One hundred thirty-six children with otitis media with effusion of at least 2 months' duration were investigated in a strict, double-blind, randomized prospective study to evaluate the efficacy of oral steroids in the treatment of this disease. The results of our study showed a significant complete and partial recovery from otitis media with effusion in the group treated by a combination of antibiotics (amoxicillin) and oral steroids (prednisone), compared with an amoxicillin-treated group and a placebo-treated group. We believe that this treatment mostly benefits children aged 4 to 10 years without oversized adenoids. The findings of our study imply that a combined course of antibiotics and oral steroids deserves its place as a routine conservative trial before surgery. PMID- 2248741 TI - Localized antigen challenge of the nasal mucosa. AB - We describe a localized nasal antigen challenge and the measurement of mediators found at the same site. Eight ragweed-allergic subjects were challenged on 2 days, 1 week apart. Challenges consisted of six sequential provocations, beginning with two control challenges (diluent for antigen-phenol-buffered saline) followed by four increasing antigen doses (0.6, 6, 60, and 160 protein nitrogen units) (antigen day) or an additional four control challenges (control day). The number of sneezes and the symptom scores increased significantly with increasing antigen doses. The levels of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased in the eluted secretions on the antigen day, but not on the control day. The amount of secretions collected also increased per unit of time on the antigen day. We found no significant increase in the concentration level of either histamine or N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions on either day. We conclude that the total amount of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased per unit of time while their concentration did not. PMID- 2248742 TI - High-resolution scanning electron microscopy of the murine olfactory receptor. AB - The anatomy of the murine olfactory receptor was analyzed using high-resolution scanning electron microscopy with the aldehyde-osmium-dimethyl sulfoxide-osmium method. A good three-dimensional image of the receptor cell architecture was obtained. Within the olfactory vesicle, a complex tubular network was found that seemed to be physically associated with adjacent organelles, the basal aspect of cilia, and the lateral plasmalemma. It is assumed that these structures may be of significance during the olfactory transduction process. PMID- 2248743 TI - The effect of chronic cocaine abuse on human olfaction. AB - Cocaine has been used for many decades as both a stimulant and as a topical anesthetic/vasoconstrictor. Illicit "snorting" or freebase smoking has increased markedly in recent years. Decreased olfaction has been an often reported subjective complaint of cocaine abusers, but quantification of smell loss using sensitive psychophysical tests has not yet been done, leading to the present study. Eleven cocaine abusers were recruited from a drug treatment clinic. Olfaction was assessed using a butanol threshold test, the UPSIT, and a 7-item discrimination test. One patient tested anosmic, one had a mild discrimination problem, and one had a large septal perforation but was normosmic. From the present study, it appears that most cocaine abusers, even heavy users or those with intranasal damage, do not develop permanent olfactory dysfunction. It is not clear what factors may have resulted in complaints of olfactory loss in previous studies. PMID- 2248744 TI - Nasal valve malfunction resulting from resection of cancer. AB - Following cancer resection of the nasal unit, nasal valve malfunction is manifested by the symptoms of nasal stuffiness or difficulty getting air into the nostril. These symptoms occur in cases in which the resection is in the alar crease at the junction with the lateral sidewall of the nose. Wound scar contracture elevates the alar margin and causes the alar and lateral cartilages to move inward forming a visible and palpable shelf on the lateral wall of the nasal vestibule. This displacement of the alar and lateral cartilages and the rigid scar formed between these cartilages render the nasal valve immobile. Since it is easier to prevent nasal valve malfunction than to repair it later, wounds that bridge the alar crease or are located in either the alae or lateral sidewall and come within 1 mm of the alar crease with a total diameter of 1.0 cm should be repaired to prevent nasal valve malfunction. In the process of repairing deep defects, the overlapping region of the lateral crus of the alar cartilage and the lateral cartilage may be stabilized by a conchal cartilage graft. This cartilage graft may be used in combination with reconstruction of the nasal skin with a forehead flap and repair of the nasal lining. In the event that the nasal lining is intact, the cartilage graft may be used with a full-thickness skin graft. PMID- 2248745 TI - Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers. AB - As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration. PMID- 2248746 TI - Rapid intraoperative tissue expansion in reconstruction of the head and neck. AB - A prolonged tissue expansion has the advantage of creating large amounts of additional skin for reconstructing cutaneous defects that might not be possible without the use of multiple, regional, distant, or microsurgical flaps. In spite of this, there are disadvantages, many of which can be circumvented by the use of rapid intraoperative tissue expansion instead. Although rapid expansion does not increase skin surface area as much as prolonged expansion, it may be helpful in assisting with closure of defects that might otherwise be problematic. PMID- 2248747 TI - Pneumocephalus secondary to a high-pressure water injury to the nose. AB - We report a case of pneumocephalus following a water jet injury to the nose incurred during a water-skiing fall. Pneumocephalus due to this type of injury has not been previously reported, to our knowledge. Since this unusual injury may be associated with serious complications, it must be promptly recognized and treated. PMID- 2248748 TI - Positron emission tomographic study of auditory sensation in a patient with a cochlear implant. AB - The speech comprehension ability of patients with a cochlear implant is fairly good even when information from the implant device is insufficient. It is presumed that the higher brain system has important roles in discriminating speech. The purpose of the present study was to investigate the function of the auditory cortices of a patient with a cochlear implant before and after sound signal inputs. In this study, we used positron emission computed tomography, which can detect brain activity by providing quantitative measurements of the metabolic rates of oxygen and glucose. Without sound signals, the auditory cortices of the patient showed remarkably low metabolic rates. However, with the cochlear implant device, the activity returned to near normal levels. These findings suggest that the activation of the speech comprehension mechanism of the higher brain system can be initiated by sound signals from the implant device. PMID- 2248749 TI - Use of the levator scapulae muscle flap in head and neck reconstruction. AB - There are numerous techniques available for reconstruction of defects following composite resection of oral cavity and oropharyngeal tumors. No single technique is applicable in all situations. The levator scapulae muscle flap is well known for its application in carotid protection. Little attention is paid to its usefulness in other aspects of head and neck reconstruction. We have been using the levator scapulae muscle flap for a variety of reconstructive problems. The flap is useful for buttressing intraoral suture lines, closing intraoral defects, and providing soft tissue to fill in dead spaces and bulk out lateral and anterior oral defects. The levator flap was found to be easy to elevate, safe, and reliable with a minimum of wound complications. A review of 18 patients, representative case studies, and a discussion of surgical technique and relevant anatomy and blood supply is presented. PMID- 2248750 TI - Parotid duct communicating with a labial pit and ectopic salivary cyst. AB - Labial pits are usually described as blind epidermal invaginations of lip mucosa with occasional drainage of minor salivary gland secretions. A case of an aberrant parotid duct in communication with both a unilateral, commissural labial pit and an interposed salivary cyst is presented. A 7-year-old boy who had experienced lifelong clear drainage from a congenital pit at his right oral commissure developed fever, pain, and a submucosal mass of the right cheek over a 6-week period. A preoperative sialogram through the pit demonstrated a communication between the oral commissure fistula, an intervening salivary cyst, and a proximal tract from the cyst to the parotid gland. An en bloc resection of the pit, fistula tract, and cyst was performed through a transoral approach. The dissection was medial to the buccinator muscle. There has been no recurrence of the cyst after 1 year follow-up. A description of labial pits and parotid duct anomalies is presented; however, to our knowledge, this combination of anomalies has not been previously described. PMID- 2248751 TI - Pathologic quiz case 2. Histiocytosis X, Letterer-Siwe variant. PMID- 2248752 TI - Excision of preauricular sinus. PMID- 2248753 TI - Operating room fire. PMID- 2248754 TI - Epidemiology of coronary heart disease and its risk factors in the USSR. PMID- 2248755 TI - Chronic idiopathic pain syndrome. AB - Chronic idiopathic pain syndrome is a common, disabling and costly condition. It is believed to be of psychological origin but may involve both cerebral and peripheral physiological mechanisms. It is often associated with depression. Its assessment and management need to be multifactorial, i.e., medical, psychosocial and psychiatric. A thorough initial medical assessment is crucially important in order to identify any organic contributory factors and to gain the patient's trust. It is also essential to carry out a psychosocial and psychiatric assessment so as to evaluate the role of psychological and socioeconomic factors and establish whether a diagnosable psychiatric disorder is present. The latter is most likely to be a depressive, anxiety, or somatoform disorder. If the medical assessment fails to come up with a plausible organic explanation for the patient's pain, he or she should be told so clearly. The patient should be told that the goal of the treatment is not to cure the pain but to help him/her improve his/her functioning and sense of control over pain and life generally. The type of management most likely to succeed in this goal is one that is multifactorial and comprehensive rather than focused on one treatment modality only. PMID- 2248756 TI - New views to the molecular pathology of osteoarthrosis. PMID- 2248757 TI - Haemodynamic effects of bopindolol and atenolol in coronary artery disease. A noninvasive study. AB - Bopindolol, a new non-selective betablocker, and atenolol, a conventional betablocker, were studied in parallel groups of eight normotensive patients with NYHA II-III angina pectoris. Non-invasive haemodynamic measurements were made using echocardiography and systolic time intervals. Drug doses were 1 mg bopindolol and 100 mg atenolol once daily; measurements were made immediately and at one and six weeks intervals. Both drugs reduced heart rate, atenolol from 62 to 47 beats/minute (24%, P less than 0.01) and bopindolol from 64 to 56 beats/minute (13%, P less than 0.05) at 24 hours. Only atenolol reduced mean blood pressure. Rate pressure product was persistently reduced by atenolol (30% at 24 hours), while with bopindolol this effect lessened with time. Opposite trends in left ventricular enddiastolic and endsystolic diameters were observed; with atenolol tending to increase and bopindolol to lower them. Atenolol had no influence on cardiac contractility, while bopindolol increased it, which was shown by enhancements in the fractional shortening, ejection fraction and maximum velocity of fibre shortening. Neither drug changed peripheral vascular resistance or systolic time intervals. Two patients on bopindolol left the study because of worsening symptoms of coronary artery disease, and two on atenolol owing to side effects, bradycardia and syncope in one and diarrhea in the other. In conclusion, bopindolol showed less beta-blocking effect than atenolol and it had a positive inotropic effect. Its benefit in treating coronary artery disease remains to be proved. PMID- 2248758 TI - Regular sauna bathing and the incidence of common colds. AB - The high morbidity of common colds means that their economic importance is considerable, with colds causing more loss of productivity than any other infection. As no effective prophylaxis is available, this trial was to test the hypothesis that sauna bathing can reduce the incidence of common colds. Twenty five volunteers were submitted to sauna bathing, with 25 controls abstaining from this or comparable procedures. In both groups the frequency, duration and severity of common colds were recorded for six months. There were significantly fewer episodes of common cold in the sauna group. This was found particularly during the last three months of the study period when the incidence was roughly halved compared to controls. The mean duration and average severity of common colds did not differ significantly between the groups. It is concluded that regular sauna bathing probably reduces the incidence of common colds, but further studies are needed to prove this. PMID- 2248759 TI - Lymphopenia in heavy drinkers--reversibility and relation to the duration of drinking episodes. AB - Seventy-four addictive alcoholic subjects were investigated shortly after a period of excessive drinking and were compared with 18 alcoholic subjects who had not been drinking for at least six months. No difference was observed in total white cell count or number of circulating granulocytes. Lymphocyte count was significantly lower in alcoholics whose last alcoholic bout had been three months or more, but after 30 days of abstinence the difference had disappeared. The depressed lymphocyte count did not correlate with other components of the drinking pattern. These results show that lymphopenia in alcoholics is a time dependent and reversible event. PMID- 2248760 TI - Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage. AB - A radioimmunoassay method for endothelin was developed. Antisera raised against endothelin 1 showed significant crossreaction with endothelin 2 and 3 (45 and 13%, respectively). Considerable endothelin immunoreactivity was shown to be present in the cerebrospinal fluid of patients with a subarachnoid hemorrhage, ranging from 0.3 pmol/l cerebrospinal fluid to 4.5 pmol/l cerebrospinal fluid, though no endothelin immunoreactivity was observed in the cerebrospinal fluid of controls and patients with cerebral infarction, subdural haematoma or brain tumours. Endothelin immunoreactivity was also observed in two out of five cerebrospinal fluid samples from patients with cerebral bleeding. Reverse phase high performance liquid chromatography showed that the main immunoreactive component in cerebrospinal fluid appeared to elute at the same position. There was, however, an immunoreactive component which eluted at the same position as endothelin 3. These results may support the idea that endothelin immunoreactivity in the cerebrospinal fluid originate mainly from endothelial and neural tissues and that endothelin may contribute to the generation of the vasospasm often observed in subarachnoid hemorrhage, a conclusion based on the exceptionally high endothelin immunoreactivity in cerebrospinal fluid observed in patients with subarachnoid haemorrhage. PMID- 2248761 TI - Mechanisms of alcohol intoxication in a rodent model: blunted alcohol-opposing reaction in "alcohol-sensitive" rats. AB - In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena. PMID- 2248762 TI - Alcohol dependence and withdrawal: a genetic animal model. AB - Using the techniques of selective breeding, mouse lines have been developed that express severe (Withdrawal Seizure Prone: WSP) or mild (Withdrawal Seizure Resistant: WSR) handling induced convulsions after cessation of chronic ethanol exposure. These lines differ at least ten-fold in severity of withdrawal after identical ethanol treatment. One feature of the genetic model is that other traits which distinguish these lines are presumably influenced by those genes determining ethanol withdrawal severity. WSP and WSR mice do not differ markedly in the metabolism of ethanol. In addition to handling induced convulsions, they also differ in other withdrawal signs: for example, WSP mice show more pronounced tremor. WSP and WSR mice do not differ in sensitivity to ethanol's hypothermic, anesthetic, or locomotor stimulant effects, nor in the magnitude of tolerance development to these responses. This suggests that sensitivity, tolerance and dependence are distinct genetic entities. WSP mice also display more severe withdrawal from diazepam, phenobarbital, and nitrous oxide than WSR mice, suggesting that some genes generally predispose mice to withdrawal from depressants. WSP mice display withdrawal handling induced convulsions after a single dose of ethanol, pentobarbital, or diazepam. The effective dose for producing drug seizures is not markedly different between WSP and WSR mice for a number of compounds with varied mechanisms of action. However, WSP mice are more sensitive than WSR mice to the effects of acute doses of convulsants to elevate handling induced convulsions. WSP mice have more binding sites in hippocampus for the N-methyl-D-aspartate antagonist MK 801. Binding of this ligand is increased during ethanol dependence in both mouse lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248763 TI - Factors regulating ethanol tolerance. AB - Ethanol tolerance is a complex phenomenon. Its development is governed by pharmacological and behavioural, as well as genetic factors. The doses of ethanol employed and the duration of ethanol treatment are important pharmacological variables. Behavioural factors such as experience of intoxication and Pavlovian conditioning may also affect the development or manifestation of ethanol tolerance. Genetic factors can influence the development of tolerance directly or/and indirectly through its influence on the initial sensitivity to ethanol. The relevance and implication of tolerance, particularly conditioned tolerance in alcohol abuse and alcoholism, are discussed. PMID- 2248764 TI - The alcohol tolerant and alcohol nontolerant rat lines selected for differential sensitivity to ethanol: a tool to study mechanisms of the actions of ethanol. AB - Genetic selection work conducted in the Research Laboratories of State Alcohol Company (Alko Ltd), Helsinki, Finland, has resulted in the establishment of the ethanol sensitive Alcohol Nontolerant (ANT) and ethanol insensitive Alcohol Tolerant (AT) rat lines which differ in their sensitivity to ethanol induced motor impairment. These lines have been used in attempts to identify the mechanisms controlling ethanol induced motor impairment. The Alcohol Tolerant rats show a lower sensitivity to ethanol induced motor impairment on a tilting plane over a wide range of doses, but the lines do not differ in all behavioral measures of ethanol sensitivity. Furthermore, the Alcohol Tolerant line shows a higher capacity to develop acute tolerance and less calm behaviour, which may contribute to the line difference. Neurochemical work has shown differences in the functioning and sensitivity to ethanol of the catecholaminergic and GABAergic systems in the two lines, suggesting a role for both of these systems in the control of ethanol induced motor impairment. PMID- 2248765 TI - Prognostic factors and long-term survival in breast cancer in a defined urban population. AB - During the years 1945-1965 461 women in the city of Turku, Southwestern Finland, were diagnosed as having a biopsy-verified breast cancer. Four-hundred and thirty nine patients (95%) with complete clinicopathologic data have now been followed up for a mean of 28 years (range from 22 to 42 years) or until death. The survival rate corrected for intercurrent deaths was 44%, 35%, and 34% 10, 20, and 30 years after the diagnosis, respectively. Only 1.2% of all deaths caused by breast cancer occurred more than 20 years after the diagnosis, and therefore about one third of the patients are likely to be cured. Fifty-six (12.8%) patients developed a second primary breast cancer or cancer of other sites. Survival of the patients diagnosed in the 1960s was better than that of the patients diagnosed earlier (p = 0.02), but the relative percentage of prognostically unfavorable poorly differentiated (Gr III) cancers became smaller with time (p = 0.009). Axillary nodal status was the most important independent prognostic factor for the 342 patients with an operable, unilateral, and invasive breast cancer in Cox's multivariate analysis (p less than 0.001), followed by histologic grade, type of tumor margin, the primary tumor size (p less than 0.001), and the extent of tumor necrosis (p = 0.003). Histologic type, mitotic count, nuclear pleomorphism, extent of tubule formation, amount of elastin, and extent of intraductal tumor growth were also significant prognostic factors in a univariate analysis. PMID- 2248766 TI - Inflammatory pseudotumor of the liver. Report of a case and literature review. AB - The radiologic and histologic features of an inflammatory pseudotumor of the liver in a 62-year-old man are presented. The lesion was coincidentally discovered during clinical work-up of an acute pancreatitis caused by choledocholithiasis. Malignancy was suspected in the light of the radiologic presentation. To our knowledge, only 23 cases of inflammatory pseudotumor of the liver have appeared in the international literature. Its etiology remains unknown, although reactive-inflammatory or infectious mechanisms have been suggested. The present case seemed to be associated with bile flow obstruction, as the mass partially regressed following cholecystectomy and Vaterian sphincterotomy. Therefore, a hypothetical obstructive pathogenetic mechanism is considered. We conclude that this tumor-like condition must be considered in the differential diagnosis of solid masses in the liver. PMID- 2248767 TI - Early response in neonatal septicemia. The effect of Escherichia coli, Streptococcus agalactiae and tumor necrosis factor on the generation of lactoferrin. AB - Using an in vitro model, we report the early effect of Escherichia coli (E. coli), Streptococcus agalactiea (group B streptococci, GBS) and recombinant tumor necrosis factor alpha (TNF) on the release of lactoferrin (LF) and the generation of interleukin-1 (IL-1) due to E. coli, using heparinized whole blood from healthy full-term newborns. We wanted to find a dose response relationship between lactoferrin generation on the one hand and the amount of E. coli, GBS and TNF on the other hand. In a final concentration of 10(7) per ml both bacteria increased the release of LF significantly. The response to E. coli was immediate and mg/l +/- 0.29 mg/l, E. coli 1.83 mg/l +/- 0.76 mg/l, p less than 0.001). GBS was a less potent stimulant than E. coli and the response was only apparent after 20 minutes (mean +/- S.D.: 1.06 mg/l +/- 0.49 mg/l, p less than 0.01). TNF in a concentration of 10000 pg/ml as well as 1000 pg/ml increased the release of LF significantly (after 20 minutes mean +/- S.D.: 1.09 mg/l +/- 0.42 mg/l and 0.97 mg/l +/- 0.36 mg/l, respectively), whereas a concentration of 100 pg/ml had no effect. Whole blood incubated with different preparations of LF for 20 minutes did not increase the generation of LF significantly. No significant changes in IL 1 levels were observed. Lactoferrin had bacteriostatic but no bactericidal effect on GBS and Streptococcus mutans. PMID- 2248768 TI - Long-term prognosis of scar and non-scar cancers of the breast. AB - The prognostic significance of histopathologic classification of ductal breast carcinoma as scar and non-scar types was studied among 311 patients with breast cancer, followed up for a minimum of 22 years after the diagnosis or until death. Ninety-six (31%) cancers were of scar type and they had a more favourable prognosis than the cancers of non-scar type (p = 0.0001). The scar cancers were more often well differentiated (p less than 0.0001), had more pronounced inflammatory cell reaction (p less than 0.0001), less nuclear pleomorphism (p less than 0.0001), less tumor necrosis (p less than 0.0001), and a lower mitotic rate (p less than 0.0001) than the non-scar cancers. It was less common for patients with scar cancer to have axillary lymph node metastases (p = 0.01) and their primary tumor was smaller (p = 0.006). In flow cytometric analysis the scar cancers were more often DNA diploid (p = 0.004) with S-phase fraction below the median (p = 0.0002). In a multivariate analysis the association of cancer with a scar did not appear as an independent prognostic factor, whereas histologic grade (p less than 0.001) and extent of tumor necrosis (p less than 0.001) did. We conclude that the classification of breast cancer as scar and non-scar types has less prognostic value than the conventional histopathologic grading. PMID- 2248769 TI - Arginine catabolism by strains of oral streptococci. AB - Arginine catabolism via the arginine deiminase pathway was found in Streptococcus sanguis 903. Citrulline and ornithine were released from resting cells incubated with arginine, arginine-containing peptides, or saliva. Maximum arginine catabolism by resting cells of S. sanguis 903 was found in the pH range 7-8 and at 45-48 degrees C. Arginine deiminase activity was found in the cytoplasm and in the cell-wall extract of this strain, while ornithine carbamoyltransferase activity was found in the cytoplasm and in extracts of cell walls and cytoplasmic membranes. Streptococcus mutans GS-5 and Streptococcus sobrinus strains OMZ 176 and 6715 could release arginine from salivary peptides but were incapable of significant arginine catabolism. PMID- 2248770 TI - Role of bacterial debris in inflammatory diseases of the joint and eye. AB - Several distinct rheumatic conditions (including Lyme arthritis, Reiter's syndrome and rheumatic fever) as well as certain forms of the blinding disease, uveitis, may share a common etiology. In each instance specific bacterial pathogens may infect a distant site, which on interaction with the immune system, leads to a sterile inflammation in the joint or eye. These "reactive" conditions may result, in some cases, from prior localization of non-viable bacterial remnants (including the cell wall or peptidoglycan) or alternatively "dormant" fastidious bacteria in the affected joint or eye where they act as persisting antigens. Classical culture techniques, would not detect the presence of these putative microbial antigens. Alternative approaches for detection of ubiquitous components of bacteria in the host (using appropriate chemical, molecular and immunological techniques) are discussed. PMID- 2248771 TI - Two cell kinetic methods studied on the rat corneal epithelium. AB - A stathmokinetic method (using Colcemid) and the [3H]thymidine technique (pulse labelling with tritiated thymidine, [3H]TdR) have been evaluated in the rat corneal epithelium. The dose is not of critical importance for the Colcemid method, thus indicating an all or nothing effect within the dose range studied. A one point estimate is sufficient to calculate the mitotic rate (MR), and in the rat corneal epithelium a 4 h accumulation period is recommended. After administration of [3H]TdR there is an increasing response with increasing dose, followed by a levelling off at higher doses. It seems reasonable to use the lowest maximal effective dose. The labelling index (LI) can be reliably registered 1 h after administration of the drug. For each of the drugs we found corresponding results after topical application and intraperitoneal injection. Hence, topical application of small doses of both Colcemid and [3H]TdR makes interesting in vivo experiments on larger animals and even on human beings possible. Due to the extreme regularity of the corneal epithelium this part of the eye is an interesting organ for cell kinetic studies and provides an excellent tool for evaluating cell kinetic methods. PMID- 2248772 TI - Isoenzymes of alkaline phosphatases in seminomas. An immunohistochemical and biochemical study. AB - Placental alkaline phosphatase (the PLAP-like isoenzyme) and liver alkaline phosphatase (LAP) were demonstrated immunohistochemically by use of monoclonal antibodies in the tumor cells of twelve seminomas and one seminoma metastasis. Intestinal alkaline phosphatase (IAP) was not found. The PLAP-like and LAP enzymes showed high catalytic activities compared to normal testis. This is the first occasion that LAP has been demonstrated by immunochemistry in seminoma cells. The results suggest that demonstration of these tumor enzymes may be useful markers for seminomas in histopathological specimens. PMID- 2248773 TI - Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study. AB - A carcinosarcoma of the stomach in a 66-year-old man is reported. The tumor which had a diameter of 4 cm was an ulcerofungating mass in the posterior wall of the antrum. Histologically it was composed of well-differentiated adenocarcinoma admixed with sarcomatous elements which showed chondrocytic differentiation on light and electron microscopy. The sarcomatous areas were multifocally scattered in the central portion of the tumor and intimately blended with adenocarcinoma cells. CEA immunoreactivity was found not only in the adenocarcinoma but also in the transitional sarcomatous cells, supporting the hypothesis that this tumor might derive from mesenchymal metaplasia of a primarily epithelial neoplasm. PMID- 2248774 TI - Potential of hypertonic medium treatment for embryo micromanipulation: I. Survival of rabbit embryos in vitro and in vivo following sucrose treatment. AB - Rabbit zygotes and embryos were exposed to hypertonic sucrose in phosphate buffered saline (SPBS). In experiment one, 144 zygotes shrank to 32-36% of their initial volume in 1.0 M SPBS within 30 min. Neither hypertonic treatment with 0.5 M or 1.0 M SPBS nor micropuncture of the zona pellucida after shrinkage affected embryo development into blastocysts in vitro (88%, 83%, and 82%, respectively), compared to that of the controls (93%, P greater than .05). In experiment two, 252 two- to four-cell- and 177 morula-stage embryos were exposed to isotonic PBS control or 0.5 M, 1.0 M, or 1.5 M SPBS for 30, 60, 90, 120, and 150 min before transfer to PBS (290 mOsm). Embryo development was significantly reduced (P less than .05) when embryos were exposed in 0.5 M and 1.0 M SPBS for more than 60 min or in 1.5 M SPBS for more than 30 min. In experiment 3, morulae exposed for 60 min to 0.5 M or 1.0 M SPBS shrank to 37-39% or 32-35% of their initial volume and then expanded to 87-94% or 81-90% of their initial volume, respectively, after being returned to isotonic PBS for 60 min, but embryos in 1.5 M SPBS had erratic osmotic behavior. In experiment four, 192 two- to four-cell embryos exposed to 0.5 M SPBS for 0, 30, and 60 min before transfer to oviducts of recipients resulted in the production of 39%, 42% and 31% young, respectively (P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248775 TI - Potential of hypertonic medium treatment for embryo micromanipulation: II. Assessment of nuclear transplantation methodology, isolation, subzona insertion, and electrofusion of blastomeres to intact or functionally enucleated oocytes in rabbits. AB - The objective of this research was to study efficiency of embryo development following transfer of blastomeres into the perivitelline space of oocytes. Single blastomeres from 8-, 16-, and 32-cell embryos were obtained following mucin coat and zona pellucida removal by combined treatments with pronase and acidic phosphate-buffered saline (PBS, pH = 2.5). Blastomeres were separated by pipetting with a fire-polished micropipette following incubation in Ca+(+)-free PBS for 15 min at 39 degrees C. This procedure resulted in over 97% blastomere separation. For ease of blastomere insertion, oocytes were placed in droplets of 0.5 M sucrose in PBS (SPBS) during micromanipulation. To functionally enucleate oocytes some were stained with Hoechst 33342 DNA stain and irradiated. A single 8 or 16-cell blastomere was aspirated into an injection pipette (35 microns or 25 microns at the tip, respectively) and inserted into the perivitelline space of an irradiated or non-irradiated oocyte, but not fused with the oocyte. This micromanipulation procedure did not affect development of individual blastomeres into blastocysts or trophectoderm vesicles when compared with cultured control single blastomeres (P greater than .05). When the inserted blastomere was induced to fuse with an intact non-irradiated oocyte under an electric field, 56-57% were fused and 39-45% of the fused and activated oocytes developed to morulae or blastocysts. When an inserted blastomere (from 8-32-cell embryos) was induced to fuse with a functionally enucleated oocyte treated by Hoechst 33342 staining, followed by washing and UV-light irradiation, 63-66% of them were fused, but only 15-22% developed to the morula or blastocyst stage. This research demonstrated that the use of hypertonic medium treated oocytes greatly improved the ease and success rate of blastomere subzona insertion, but the value of functionally enucleated oocytes as recipient cells for nuclear transfer requires further investigation. PMID- 2248776 TI - Ultrastructure of porcine embryos following development in vitro versus in vivo. AB - The present study examined the ultrastructural appearance of porcine embryos from the four-cell stage to the blastocyst grown either in vivo or in vitro. Embryos were collected at slaughter from superovulated gilts and were fixed for transmission electron microscopy either immediately or after various periods of in vitro culture. In general, the morphology of in vivo and in vitro grown embryos was similar. In vivo grown four-cell stages contained dense fibrillar nucleoli. At the eight-cell stage the nucleoli possessed increasing amounts of chromatin and granules. In both stages the mitochondria were spherical or ovoid in shape and had only few cristae. In morulae and blastocysts the nucleoli were mainly of the fibrillogranular type, and the mitochondria were filamentous and possessed more cristae, of which many were tubular. Two major ultrastructural deviations were observed in about half of the in vitro cultured embryos. First, nucleolus-like structures were found outside the nuclei in the cytoplasm of blastomeres. These structures were spherical and composed of chromatin-like material containing characteristically a single large and several small vacuoles. The structures were frequently associated with profiles of smooth endoplasmic reticulum (SER). A second type of deviation was aggregates of SER appearing as spiral coils or multiangular complexes. Some embryos displayed both types of deviations. The physiological significance of these deviations remains speculative. They may be involved in the considerably reduced capability of porcine embryos to develop to piglets following in vitro culture. PMID- 2248777 TI - Relationships between follicular fluid steroid hormone concentrations, oocyte maturity, in vitro fertilization and embryonic development in the rhesus monkey. AB - Oocytes and matched samples of follicular fluid (FF) were obtained from 70 follicles of five rhesus monkeys stimulated with either pregnant mare serum gonadotropin or human menopausal gonadotropin. Follicular aspiration was performed 30-32 h after human chorionic gonadotropin administration. The concentrations of estradiol (E2), progesterone (P), testosterone (T), and dihydrotestosterone (DHT) in FF were measured. Twenty-six percent of oocytes were classified as mature (M), 41% matured in vitro (Miv), 13% were dysmature, and 20% atretic. M oocytes were associated with significantly higher levels of P and a higher P:E2 ratio. There were no differences in hormone levels associated with fertilized and nonfertilized oocytes. Thirty-five embryos developed to the six- to eight-cell stage in vitro, of which 13 exhibited optimal cleavage rates. Significantly lower levels of E2 and higher P:E2 ratios were associated with the more rapidly cleaving embryos. Proportionally more embryos showing optimal cleavage rates developed from M compared to Miv oocytes, and only embryos derived from M oocytes developed to blastocysts in culture. Optimal cleavage rates to the six- to eight-cell stage in vitro, rather than fertilization rates, are a better indicator of (subsequent) developmental capacity, and, in this study, embryonic development was closely associated with the maturity of the oocyte at recovery. PMID- 2248778 TI - Acrosome reaction of stallion spermatozoa evaluated with monoclonal antibody and zona-free hamster eggs. AB - The acrosome of the stallion spermatozoon was visualized by indirect immunofluorescence with monoclonal antibody (18.6) which recognized an integral acrosomal membrane component. Localization was confirmed by electron microscopy using peroxidase labelled antibody. In fresh semen samples (n = 19), 73.9 +/- 9.1% of the spermatozoa from five fertile stallions displayed a uniform bright fluorescence over their acrosome region. In two semen samples from an infertile stallion only 28% and 35% of spermatozoa showed the same pattern of fluorescence. Spermatozoa from fertile stallions incubated for up to 12 hours in TALP medium maintained motility and exhibited a significant progressive loss of acrosomes as detected by immunofluorescence. Alternatively, a similar loss of acrosomes could be induced with calcium ionophore A23187 over a 90 minute incubation. Ultrastructural observations and incubation with zona-free hamster eggs indicated that only with ionophore treatment was immunofluorescent acrosome loss correlated with a physiological acrosome reaction, while prolonged sperm incubation led to degenerative membrane changes. It was concluded that, if carefully validated, immunofluorescent localization of the acrosome of stallion sperm with monoclonal antibody could be used to monitor the acrosome reaction. Furthermore, definitive acrosome visualization would be valuable in assessing semen quality. PMID- 2248779 TI - Sperm DNA and sex chromosome differences between two geographical populations of the creeping vole, Microtus oregoni. AB - The relative DNA content of the "O" and Y chromosome-bearing sperm is presented for the creeping vole, Microtus oregoni. The animals had been trapped in Oregon and in Washington State. The two populations had very similar autosomal chromosome relationships but differed greatly in the size of their X chromosome (which is not carried by vole sperm) and in their Y chromosome. The greater size and banding differences of the Y chromosome of the Washington State vole compared to the Oregon vole paralleled the greater differences in sperm DNA between the Y bearing sperm and the sperm carrying no sex chromosome (O). The actual DNA differences between O and Y sperm was 12.5% for the sperm from the Washington State voles and 9.1% for sperm from the Oregon voles. The difference in sperm DNA content (12.5%) for Washington State voles was far greater than the difference shown for other voles or other mammals. PMID- 2248780 TI - Effect of microinjection and two types of electrical stimuli on bovine sperm hamster egg penetration. AB - These experiments were designed to test the effects of an electrofusion and an electroporation pulse on bovine sperm-hamster egg development. In experiment 1, single motile sperm were injected into the perivitelline space of each egg. A 4,500 V/cm, 30 microseconds fusion pulse (FP) was applied while sperm-egg membrane contact was maintained. It was observed that single motile sperm were rendered immotile immediately after FP application whereas nonpulsed single motile sperm remained motile for up to 36 h postinjection. In addition, both motile and sonicated spermatozoa were injected directly into the ooplasm prior to receiving an FP to determine whether the FP was detrimental to sperm viability. In experiment 2, to induce the acrosome reaction, an 1,150 V/cm electroporation pulse was applied to washed bovine sperm suspended in TALP medium containing 5 mM Ca2+. Treated and nontreated sperm were coincubated with zona-free hamster ova, and sperm-pentrating ability was measured. Results from experiment 1 indicate that FP failed to induce sperm-egg fusion (0/69). FP did not, however, inhibit decondensation or pronuclear formation of sperm injected into hamster egg ooplasm. Single motile sperm injected into the ooplasm resulted in development of both pulsed (19/28) and nonpulsed (21/28) groups. Sonicated tail-free sperm heads injected into the ooplasm resulted in no detectable difference between treated (18/30) and nontreated (19/30) groups. In experiment 2, treatment of sperm with electroporation pulse +5 mM Ca2+ increased zona-free hamster ova penetration scores over nontreated sperm within bulls (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248781 TI - Chromosome constitution of highly motile mouse sperm. AB - In this study, we address the relationship between motility and genetic content of mouse sperm. The chromosome complements of highly motile mouse sperm, selected using the swim-up technique, were analyzed after in vitro fertilization, at the first cleavage state. They were compared to those of unselected sperm. Identification of male and female chromosome sets was possible because of their differential condensation at the first mitotic division. In vitro fertilization, swim-up separation, chromosome preparation, and staining were carried out using standard techniques. The results indicate that highly motile mouse sperm did not differ in types and frequencies of chromosomal abnormalities from those not selected for motility. Moreover, separation of motile sperm does not deviate the sex ratio from the theoretical 1:1. PMID- 2248782 TI - Response to "Leitz IVF II incubator performance". PMID- 2248783 TI - Does the T gene determine the anteroposterior axis of a mouse embryo? AB - The t complex in the mouse is essential to embryonic development. The semidominant mutation, T, is embryonic lethal in homozygotes. In T/T embryos, proper morphogenetic movement is hindered, causing the number of mesodermal cells to be reduced. The other effect of T mutation is shortening of the tail in heterozygotes, T/+ and T/t. t is a series of recessive mutations in the t complex. A detailed examination of tail shortening indicated the T and t mutations to exert various effects, such as the derangement of the pattern of necrosis, fusion or duplication of the neural tube and gut. The most severely affected structure is the notochord. The t mutation augments the effect of T mutation in the formation of normal notochord. A gradient of phenotypic severity along anteroposterior axis of an embryo appeared to exist correlative to the dosage of the T gene. Should the products of the T gene be responsible for inducing mesoderm and the establishment of the anteroposterior axis of an embryo, diverse effects of the T mutation on embryogenesis can be explained collectively. PMID- 2248784 TI - Structural and functional stability of IncP plasmids during stepwise transmission by trans-kingdom mating: promiscuous conjugation of Escherichia coli and Saccharomyces cerevisiae. AB - In order to establish a gene transfer system for yeast by promiscuous conjugation, we constructed plasmid pAY101 which contained an oriT sequence derived from RK2 (IncP) and the yeast TRP1 and ARS1 genes. A conjugation mixture consisted of yeast Saccharomyces cerevisiae, E. coli harboring pAY101, and E. coli carrying a helper plasmid with mob and tra. In the conjugation mixture a tryptophan-requiring yeast mutant (trp1) was converted to be prototrophic for tryptophan at a frequency of about 10(-5) to 10(-3) per recipient cell. This E. coli-yeast conjugation system required the mob, tra, oriT, TRP1 and ARS1 genes. The mob and tra genes were trans-acting elements as in an E. coli conjugation system. The mobilization was inhibited by nalidixic acid as in a typical bacterial conjugation. DNA analysis indicated that the plasmid pAY101 was transferred from E. coli to S. cerevisiae, and retained its original structure and function in yeast host cells. PMID- 2248785 TI - Genetic analysis of variation in the number of primary spermatocytes per cyst in Drosophila virilis. AB - Two experiments were performed with the aim of clarifying the genetic basis of variation in the number of primary spermatocytes per cyst in the B12 strain of Drosophila virilis and identifying the chromosome responsible for the variation. First, crosses between B12, showing a mean cell number of 11.81, and strain TK with a mean of 7.91, were performed. From the results obtained, it was considered that there were two factors, i.e., a recessive gene and certain modifiers, which shifted the cell number toward a higher value in B12. Second, chromosomal analysis with a marker strain and the B12 strain revealed that the third chromosome of B12 was responsible for the major effect of changing the primary spermatocyte number, although this chromosome did not exert a sufficient effect alone, and furthermore that at least one of the modifiers located on the second chromosome. PMID- 2248786 TI - [Atrial pacing in the evaluation of coronary disease]. AB - In order to assess the value of atrial pacing in the diagnosis of myocardial ischemia, 23 patients (mean age 53 +/- 8 years), submitted to coronary angiography, were studied. Atrial Pacing at incremental frequencies was performed until the appearance of electrocardiographic changes (ST segment depression) and/or typical anginal pain. The highest frequency of stimulation was 160/min. The test was negative in four of five patients (80%) without significant obstructive coronary artery disease. Atrial pacing test was positive in 17 of 18 patients (94%) with abnormal angiography. The authors concluded that clinical and ECG abnormalities induced by atrial pacing seems to be correct indicators for the diagnosis of myocardial ischemia. This test can be an useful alternative in patients unable to perform a conclusive stress test. PMID- 2248787 TI - [Diagnosis of silent ischemia in patients with previous myocardial infarct, under 45 years of age]. AB - STUDY OBJECTIVE: Diagnostic methods validation and incidence estimation of silent myocardial ischemia in patients with previous myocardial infarction under 45 years. DESIGN: Prospective in comparison with a healthy group. SETTING: Cardiac outpatients follow-up at Faro's District Hospital. PATIENTS AND PARTICIPANTS: A random group of 23 outpatients (GI) under 45 years, with previous myocardial infarction. A second group of healthy volunteers (GII) similar in age and sex. INTERVENTIONS: After discontinuing therapy, a maximal treadmill exercise test (E.T.) was performed in both groups, using the Bruce protocol. A ST segment depression greater than or equal to 1 mm, measured 80 ms after J point was the positive criteria. Simultaneously a 24 h Holter recording was obtained using a two channel real time recorder. ST segment depression greater than or equal to 1 mm, measured 80 ms after J point and lasting over 60 s., was the positive criteria. Patients with left bundle branch block or left ventricular hypertrophy criteria were excluded. Concerning ventricular arrhythmias only repetitive forms were considered. MEASUREMENTS AND RESULTS: Ten E.T. (43.5%) resulted positive in GI. Simultaneous Holter recording was positive in nine patients (one false negative). From the 13 patients with negative E.T., 12 had negative Holter recordings (one false positive). Every E.T. and simultaneous Holter resulted negative in GII. Silent ischemia was detected in eight GI patients (34.8%) all of them belonging to the subgroup with positive E.T. In four patients the silent ischemia was detected by asymptomatic E.T., and simultaneous Holter. The remaining four patients had silent ischemia diagnosed on the subsequent Holter. Silent ischemia episodes were not detected in the subgroup of 13 patients with negative E.T. Between those two subgroups it is highly significant (p less than 0.001) the difference in the incidence of silent ischemia. The patients with silent ischemia recorded an average of 6.5 episodes/patient/day mainly in day time (p less than 0.001). Episodes of silent ischemia were more frequent in the subgroup of patients with asymptomatic positive E.T. than in the subgroup of positive E.T. with pain (p less than 0.004). It was not confirmed any significant difference in the incidence of ventricular arrhythmias among patients with or without silent ischemia. CONCLUSIONS: We have verified an high incidence of silent ischemia in a group of patients with previous myocardial infarction. Holter's electrocardiographic monitoring has a high concordance with E.T. results, when performed simultaneously. In fact, it does not provide any significant additional information since every patient with silent ischemia had positive E.T., but can be complementary in the evaluation of the total ischemic burden. It has been checked that episodes of silent ischemia have a major incidence at day time, appearing more often in patients with asymptomatic positive E.T. PMID- 2248788 TI - [Postoperative left ventricle-right auricle fistula: a case report]. AB - We present a case of a postoperative left ventricular--right atrial shunt in a 46 year-old patient operated for aortic valvulopathy. Through two-dimensional echocardiography and hemodynamic studies a communication between the left ventricle and the right atrium was observed. We review the literature about this rare anomaly. PMID- 2248789 TI - [Clinical decision analysis. Contribution of economic aspects to the decision making process. II--Practical application of the decision threshold technique]. PMID- 2248790 TI - [Tachyarrhythmia]. PMID- 2248791 TI - [Bradyarrhythmia]. PMID- 2248792 TI - [Left ventricular insufficiency]. PMID- 2248794 TI - [Surgical treatment of variant angina]. PMID- 2248793 TI - [Residual ischemia, angina and re-infarct]. PMID- 2248795 TI - A radical-chemical route to acetyl-CoA: the anaerobically induced pyruvate formate-lyase system of Escherichia coli. AB - Anaerobically growing Escherichia coli cells contain the enzyme pyruvate formate lyase which catalyses the non-oxidative cleavage of pyruvate to acetyl-CoA and formate. The enzyme is subject to interconversion between inactive and active forms. The active form contains an oxygen-sensitive organic free radical located on the polypeptide chain which is essential for catalysis. It affords a novel homolytic C-C bond cleavage of the pyruvate substrate. The radical is generated by an iron-dependent converter enzyme which requires reduced flavodoxin and adenosyl methionine as co-substrates and pyruvate as a positive allosteric effector. A second converter enzyme, also iron-dependent, accomplishes the removal of the radical. This post-translational interconversion cycle controls the activity state of pyruvate formate-lyase in the anaerobic cell. Anaerobic conditions also regulate pyruvate formate-lyase at the level of gene expression. Multiple promoters are responsible for effecting a twelve to fifteen fold induction and they are coordinately controlled in response to the oxygen and metabolic status of the cell by sequences which are located far upstream of the pfl coding region. The transcription factor Fnr has been identified as being responsible for part of the anaerobic control of pfl expression, probably through direct interaction with the upstream sequences. In contrast, the expression of the gene encoding the first iron-dependent converter enzyme is unaffected by anaerobiosis and is independent of the Fnr protein. PMID- 2248796 TI - FNR and its role in oxygen-regulated gene expression in Escherichia coli. AB - Bacteria which can grow in different environments have developed regulatory systems which allow them to exploit specific habitats to their best advantage. In the facultative anaerobe Escherichia coli two transcriptional regulators controlling independent networks of oxygen-regulated gene expression have been identified. One is a two-component sensor-regulator system (ArcB-A), which represses a wide variety of aerobic enzymes under anaerobic conditions. The other is FNR, the transcriptional regulator which is essential for expressing anaerobic respiratory processes. The purpose of this review is to summarize what is known about FNR. The fnr gene was initially defined by the isolation of some pleiotropic mutants which characteristically lacked the ability to use fumarate and nitrate as reducible substrates for supporting anaerobic growth and several other anaerobic respiratory functions. Its role as a transcriptional regulator emerged from genetic and molecular studies in which its homology with CRP (the cyclic AMP receptor protein which mediates catabolite repression) was established and has since been particularly important in identifying the structural basis of its regulatory specificities. FNR is a member of a growing family of CRP-related regulatory proteins which have a DNA-binding domain based on the helix-turn-helix structural motif, and a characteristic beta-roll that is involved in nucleotide binding in CRP. The FNR protein has been isolated in a monomeric form (Mr 30,000) which exhibits a high but as yet non-specific affinity for DNA. Nevertheless, the DNA-recognition site and important residues conferring the functional specificity of FNR have been defined by site-directed mutagenesis. A consensus for the sequences that are recognized by FNR in the promoter regions of FNR-regulated genes, has likewise been identified. The basic features of the genes and operons regulated by FNR are reviewed, and examples in which FNR functions negatively as an anaerobic repressor as well as positively as an anaerobic activator, are included. Less is known about the way in which FNR senses anoxia and is thereby transformed into its 'active' form, but it seems likely that cysteine residues and possibly a metal ion are involved. Four of the five cysteine residues of FNR are clustered in an essential N-terminal 'domain' which is conserved in FNR and the HlyX protein of Actinobacillus pleuropneumoniae, but not in CRP or the FixK protein of Rhizobium meliloti. The relationships between FNR and other oxygen related systems in E. coli are discussed, as well as parallel systems in other organisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2248797 TI - Passive smoking in utero: no objective morphogenetic changes in the neonate. AB - The relationship between smoking during pregnancy and minor morphogenetic and anthropometric variants of the fetus was investigated in a case-control study. Sixty infants of mothers admitting to have smoken more than 20 cigarettes a day during pregnancy were matched to 120 infants of non-smoking mothers. No differences in the prevalence of 54 informative morphogenetic variants and in the values of 31 anthropometric measurements and indices were found. PMID- 2248798 TI - The problem of comparative analysis of birth prevalence of congenital cardiovascular malformations. AB - A number of published papers have dealt with the comparison of birth prevalences of congenital cardiovascular malformation (CCVMs). The feasibility of meaningful intercountry comparison was explored during the visiting fellowships to Dr Andrew Czeizel of Charlotte Ferencz and Dr Francine Lys. Data from three Hungarian studies, one USA and one Belgian study are presented here for selected CCVMs. Differential perinatal and diagnostic circumstances which lead to possible causes of bias involve four main domains: study population, ascertainment of cases, categorization of CCVMs and diagnostic definitions. Unique features are highlighted as a descriptive framework which will promote the comparability of epidemiologic data from various regions. PMID- 2248799 TI - Placental villous edema: a possible cause of antenatal hypoxia. AB - This study was undertaken to determine the relationship between the placental villous edema and the characteristic sequelae of antenatal hypoxia, i.e. the need for resuscitation at birth and low pH values in umbilical arterial blood. Placental villous edema was recognized by finding of open spaces within the cytoplasm of intervillous cells and in the interstitium of the villi. The percentage of edematous villi was significantly higher in the group of newborns requiring resuscitation. The severity of the edema had a positive correlation with the need for resuscitation at birth and with the arterial blood pH values in the umbilical cord. Placenta praevia and maternal toxicosis were associated with high percentage of edematous villi. It is suggested that edema fluid interposed a barrier to gas exchange between mother and fetus. The capillaries were blocked by compression leading to reduction in blood flow through the villi. These abnormalities, if widespread, may reduce gas exchange. It is suggested that hypoxia could partly be prevented by preventing the development of placental villous edema. PMID- 2248800 TI - Serum antioxidant activity in premature babies. AB - Autooxidation of bovine-brain homogenate proved to be a good model to determine the antioxidant capacity of sera. It was measured in parallel with the level of ceruloplasmin and apotransferrin in sera of 35 healthy children and 20 premature babies (gestational age 28-33 weeks). Antioxidant capacity was very low in premature babies with a nadir on the 4th postnatal day. Lipid-peroxidation of bovine-brain homogenate could be inhibited in vitro by the addition of exogen antioxidant. In this assay MTDQ-DS, Cavinton, DPA-HC1, vitamin E, A, C showed different antioxidant activity. PMID- 2248801 TI - Early postnatal changes of immunoglobulin levels in very low birth weight (less than or equal to 1500 g) preterm infants. AB - Immunoglobulin levels were measured in 16 very low birth weight preterm infants (birth weight: 1091 +/- 221 g, gestational age: 28.8 +/- 1.6 wks, mean +/- SD) at birth and at postnatal ages of 2, 4, 6 and 8 weeks. IgM level increased significantly by the age of 2 weeks (0.26 +/- 0.25 g/l vs 0.76 +/- 0.45 g/l, p less than 0.05), then remained unchanged throughout the study period. IgA level did not change significantly. IgG level decreased significantly by the age of 6 weeks (6.04 +/- 3.8 g/l vs 4.4 +/- 1.4 g/l, p less than 0.05), but after that no further decrease could be detected. The extent of the decrease in IgG level, however, proved to be smaller than expected on the basis of the reference data for term infants. The possibility is suggested that the packed red cell transfusions given to the patients may have resulted in the higher immunoglobulin levels. PMID- 2248802 TI - Red blood cell electrolyte changes in patients with juvenile diabetes mellitus. AB - The sodium and potassium concentrations of the red blood cells and the serum were investigated in 21 children with diabetes mellitus. Measurements were made prior to and 1 and 2 hours following insulin administration. Before insulin treatment, the sodium level in the red blood cells of the diabetes patients was significantly higher that the control level, while the potassium level was significantly depressed. These differences were not observed 1 and 2 hours following insulin administration. Attention is drawn to the rapid and extensive electrolyte changes in the red blood cells of diabetics in response to insulin. The potassium content of the serum of the diabetics was significantly decreased by insulin administration. No correlation was found between the electrolyte levels and the fasting blood glucose levels. A weak negative correlation (p less than 0.02) was observed between the potassium content of the red blood cells and the duration of the illness. The pathogenetic, diagnostic and therapeutic implications of the results are discussed. PMID- 2248803 TI - Peroxide haemolysis of erythrocytes in children with diabetes mellitus. AB - Peroxide haemolysis of erythrocytes in children with diabetes mellitus was discussed. The peroxide haemolysis tests of erythrocytes of 32 healthy and 35 diabetic children were compared. The erythrocytes of diabetics were hemolyzed to a small extent when 2% H2O2 was used. If 5 and 10 mmol/l glucose were added, the peroxide haemolysis of the controls decreased but that of the diabetics did not change. The results of the examinations performed with pH 6.8 were compared to those of pH 7.4 and both in the diabetics and controls a slight haemolysis was observed. PMID- 2248804 TI - Peripheral blood lymphocyte subpopulations in children with juvenile chronic arthritis. AB - Peripheral blood lymphocyte subset levels were analyzed in 28 patients with active, polyarticular, juvenile chronic arthritis and in 12 healthy control children. The patients with a similar treatment were divided into two groups, at the beginning of disease and after five years' course. Ten children with juvenile chronic arthritis were treated by glucocorticosteroid. After five years the percentage of active T cells, T suppressor cells and active/total T cells ratio were significantly elevated and there was a decrease in the T4/T8 ratio. Glucocorticosteroids increased the proportion of active T cells but did not change the percentage of other lymphocyte subsets. It is concluded that during the course of disease a drug-induced or spontaneous process appears which corrects the initial immunological disturbance. PMID- 2248805 TI - Early relapses of varicella-zoster virus infection in immunocompromised children treated with acyclovir. AB - Authors observed one or more early VZV relapses in 8 out of 98 Acyclovir treated immunocompromised children with varicella. None of the 8 children developed VZV antibodies by the end of the 5-day ACV treatment. All VZV relapses were successfully treated with ACV or Vidarabine, but were stopped only after the appearance of VZV antibodies in the patients' sera. The possible role of ACV treatment in pathogenesis of early VZV relapses could be excluded by comparing the VZV antibody production of patients treated with ACV from the first day of varicella on with the antibody response of those, who received ACV as late as on the 5th day of varicella. By prolonging the ACV treatment till the appearance of VZV antibodies, early relapses could be avoided. PMID- 2248806 TI - Prognostic value of chromosome aberrations in childhood acute lymphoid leukemia (ALL). AB - Cytogenetic analyses were performed on 43 children with acute lymphoblastic leukemia (ALL) before starting the therapy. Evaluable metaphases were obtained in 26 cases (60.46 %). The prognostic value of the initial chromosome picture and that of the different non-cytogenetic prognostic features was studied. In 14 out of 26 children (53.85 %) clonal chromosomal aberrations were found. The prognosis in the normal and normal/abnormal groups was significantly better than in patients with only abnormal cells. They found the remission rate of the diploid and hyperdiploid groups to be better and the survival duration significantly longer than in the pseudodiploid patients. Studying the correlation between the cytogenetic and non-cytogenetic findings the diploidy and hyperdiploidy seems to associate with low risk factors, while pseudodiploidy with high risk factors. When opposite cytogenetic and non-cytogenetic prognostic parameters were associated, the outcome of disease was determined by the cytogenetic picture. In eight patients out of the 14 children with abnormal karyotype various specific aberrations were found. While patients with specific translocations had a poor prognosis, the prognosis of the patients with 6q- was relatively good. The findings support the necessity of chromosome examination in all the children with ALL at diagnosis in order to distinguish the poor risk patients from the good ones. PMID- 2248807 TI - Cell membrane fluidity in blast cells of children with acute leukaemia. AB - Plasma membrane fluidity has been investigated by determining steady-state fluorescence polarization (FP) of the apolar stain 1,6-diphenyl-1,3,5,-hexatriene in intact blast cells, separated from peripheral blood and bone marrow of children with various types of acute leukaemia. FP-values of blast cells taken before antileukaemic therapy were compared with FP-values of peripheral blood and bone marrow mononuclear cells separated from patients in complete remission as well as from control patients and from healthy volunteers. Moreover, fluorescence polarization measurements were also performed using blast cells of leukaemic patients on short-term single-drug prednisolone pretreatment. The results have shown that untreated blast cells have significantly lower FP-values than normal mononuclear cells of peripheral blood or bone marrow. No compartment difference has been observed within blast cells, while normal mononuclear cells from peripheral blood have significantly higher FP-values than bone marrow cells. FP values of cells separated in remission or during prednisolone treatment do not differ from control values. PMID- 2248808 TI - Increased number of chromosome aberrations in the peripheral blood culture of a retinoblastoma patient. AB - Chromosome studies were performed on blood lymphocytes from an eight-year-old patient whose left eye had been enucleated earlier because of retinoblastoma. GTG banded karyotypes showed both numerical and structural chromosome aberrations, and the number of the patient's lymphocytes with chromosome aberration increased. It was concluded that retinoblastoma survivors need continuous control because of the increased risk of second primary tumors. PMID- 2248809 TI - Provocation of convulsive activity in the EEG by promazine-HCl-induced sleep in children. AB - The authors report on the convulsive activity provoking effect of Promazine as shown on EEG during sleep. It has successfully been used in infants and children who do not tolerate sleep deprivation. Promazine had smaller effect on the EEG pattern than other related compounds or barbiturates. The greatest efficacy could be reached in generalised epilepsy, but the method was also helpful in other epilepsies. It is emphasized that in cases of acute neurological symptoms of not epileptical origin the compound is helpful to exclude epilepsy since Promazine induced sleep was never associated with convulsive activity on EEG in these cases. PMID- 2248810 TI - Glomerulocystic kidney. A case report. AB - This paper presents a rare type of renal cystic disease involving the Bowman's capsule: the glomerulocystic disease associated with multiple malformation. Etiology or pathogenesis of glomerulocystic kidney remained unclear. PMID- 2248811 TI - Ketorolac trometamol--a new non-opioid analgesic. PMID- 2248812 TI - Comparison of i.m. ketorolac trometamol and morphine sulphate for pain relief after cholecystectomy. AB - I.m. ketorolac trometamol 30 mg was compared with morphine sulphate 10 mg after cholecystectomy in a double-blind, multiple dose, randomized study of 100 patients. Assessments of pain were made immediately after operation (day 1), and the next morning (day 2). Pain intensity (verbal response score and visual analogue scale) was recorded before injection and then over a 6-h period. Pain relief was assessed also. The effect of ketorolac on operative blood loss and platelet function was examined. Time to commencing oral intake and the duration of administration of i.v. fluids were recorded. Adverse events were noted. Ketorolac produced significantly less analgesia than morphine on day 1, but on day 2 the two drugs produced a similar effect. Blood loss was not increased by ketorolac, although platelet function was impaired. Repeated i.m. administration of ketorolac did not produce any serious adverse effects. PMID- 2248813 TI - Effects of ranitidine and metoclopramide on gastric fluid pH and volume in children. AB - To determine the effects of ranitidine and metoclopramide on gastric fluid in children, 40 healthy children (aged 2-8 yr) were allocated randomly to groups of 10 to receive one of four oral premedications 4 h before surgery: no premedication, metoclopramide 0.1 mg kg-1, ranitidine 2 mg kg-1 and metoclopramide 0.1 mg kg-1 with ranitidine 2 mg kg-1. After tracheal intubation, gastric fluid was aspirated and analysed for pH and total fluid volume. Ranitidine, with or without metoclopramide, increased gastric fluid pH significantly compared with control (P less than 0.05). Gastric fluid volume did not change significantly. PMID- 2248814 TI - Complications of nasotracheal intubation in neonates, infants and children: a review of 4 years' experience in a children's hospital. AB - A computerized database was set up to study the incidence and outcome of complications of nasotracheal intubation in a paediatric hospital. We studied 2953 intensive care admissions over a 4-yr period. The overall complication rate was 8%. Accidental extubation and tube blockage were the most frequent events, accounting for a mean of 3.5% and 2.6% of the complications per year, respectively. Complications were more common in smaller children and there were differences between fields of intensive care. None of the complications was fatal or resulted in serious sequelae. None of the children in the study showed clinical symptoms of acquired subglottic stenosis before discharge from hospital, and none has been readmitted for this condition subsequently. PMID- 2248815 TI - Pharmacokinetics of an infusion of propofol during cardiac surgery. AB - We have measured whole blood concentrations and pharmacokinetics of propofol administered as a constant rate infusion during cardiac surgery. Ten patients undergoing elective cardiac surgery involving cardiopulmonary bypass (seven myocardial revascularization and three aortic valve surgery) received a continuous infusion of propofol 4 mg kg-1 h-1 to supplement alfentanil analgesia. Whole blood propofol concentrations were measured by high pressure liquid chromatography. A concentration greater than 1 microgram ml-1 was achieved within 15 min of starting the infusion and remained constant throughout surgery. Volume of distribution, clearance and terminal half-life were similar to those found in non-cardiac patients. PMID- 2248816 TI - Preoperative piroxicam for postoperative analgesia in dental surgery. AB - Fifty patients were allocated randomly to receive placebo or piroxicam 40 mg, 2.5 h before surgical removal of lower third molars under general anaesthesia. A significantly greater number of patients in the piroxicam group did not require opioid analgesia after operation (P less than 0.05). The piroxicam group also required fewer doses of paracetamol in the first 24 h after recovery from anaesthesia (P less than 0.05), and the time from recovery to first postoperative analgesia was longer in those patients who had received piroxicam (P less than 0.05). Piroxicam did not significantly prolong the duration of recovery from anaesthesia. PMID- 2248817 TI - Spinal anaesthesia with plain 0.5% bupivacaine at 19 degrees C and 37 degrees C. AB - Forty-five men aged 50-80 yr undergoing urological surgery under spinal anaesthesia were allocated randomly to three groups. All patients received 0.5% plain bupivacaine 3 ml injected at the L2-3 interspace. The temperature of the solution in group 1 was 19 degrees C, in groups 2 and 3 37 degrees C. In groups 1 and 2 the injection was performed with the patient sitting; in group 3 the patient was in a lateral horizontal position. Spread of block, intensity of motor block and cardiovascular stability were measured. Warming the solution from 19 degrees C to 37 degrees C before spinal injection with the patient in the sitting position did not significantly affect these variables. However, the extent of analgesia was reduced significantly when the 37 degrees C solution was injected with the patient in the lateral horizontal compared with the sitting position. PMID- 2248818 TI - Effect of extradural compliance and resistance on spread of extradural analgesia. AB - We have studied the effect of extradural compliance and extradural resistance on the spread of extradural analgesia. In 111 patients aged 21-75 yr, compliance and resistance of the extradural space were calculated by a mathematical analysis (using the Windkessel theory) of the extradural pressure-response curve to injection of a given volume of local anaesthetic. The calculated mean extradural compliance was 0.39 (SD 0.13) ml mm Hg-1 and this increased with advancing age (P less than 0.01). The total number of analgesic segments blocked was related to extradural compliance (P less than 0.01). Segmental dose requirement was related inversely to extradural compliance (P less than 0.01). Calculated extradural resistance was 26.8 (14.5) mm Hg s ml-1 and this decreased with advancing age (P less than 0.05). The total number of analgesic segments blocked was related inversely to extradural resistance (P less than 0.05). Segmental dose requirement was related to extradural resistance (P less than 0.05). PMID- 2248819 TI - Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery. AB - Thirty-five patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) were allocated randomly in a prospective double-blind study to receive either nimodipine 0.5 micrograms kg-1 min-1 or placebo. Cerebral blood flow (CBF) was measured during and immediately after CPB. Neuropsychological tests were performed 6 months after surgery to determine any relationship between ischaemic damage and CBF and administration of nimodipine. There were no differences in CBF between the nimodipine (n = 18) and placebo groups (n = 17). Significant changes in neuropsychological tests were found in six patients tested 6 months after surgery but there were no conclusive signs of ischaemic damage. The nimodipine treated group performed better in tests of verbal fluency and visual retention, suggesting that some memory functions were preserved better in this group. PMID- 2248820 TI - Functional and metabolic effects of bupivacaine and lignocaine in the rat heart lung preparation. AB - We have examined the effects of bupivacaine and lignocaine on myocardial metabolism in the rat isolated heart-lung preparation. Bupivacaine 1, 5 or 25 micrograms ml-1 or lignocaine 4, 20 or 100 micrograms ml-1 was administered 5 min after the start of perfusion. Both bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 reduced heart rate significantly. Bupivacaine 25 micrograms ml-1 was associated with a higher incidence of arrhythmias than the other groups. Three hearts in the bupivacaine 25 micrograms ml-1 group (n = 8) and two hearts in the lignocaine 100 micrograms ml-1 group (n = 8) failed (zero cardiac output) at the end of the experiment. Although there were no significant differences in myocardial lactate and glycogen concentrations between groups, ATP content in the bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 groups was significantly less than that in the control group. The results suggest that myocardial depression and subsequent metabolic deterioration occurred with both the high doses of local anaesthetics; these findings do not account for the apparent increased cardiotoxicity of bupivacaine. PMID- 2248821 TI - Desflurane and sevoflurane: inhalation anaesthetics for this decade? PMID- 2248822 TI - Effect of adrenaline on plasma concentrations of bupivacaine following intra articular injection of bupivacaine for knee arthroscopy. AB - We administered 0.5% bupivacaine 30 ml either with or without adrenaline 5 micrograms ml-1 randomly to 16 healthy outpatients, to determine the efficacy of local and intra-articular local anaesthesia for knee arthroscopy and whether or not adrenaline should be added to intra-articular bupivacaine. Bupivacaine concentrations were measured in plasma obtained 15, 30, 45 and 60 min after intra articular injection. Patients receiving bupivacaine with adrenaline had significantly smaller plasma concentrations of bupivacaine at all times than did patients receiving plain bupivacaine. The maximal concentrations of bupivacaine in the plain group (median 515 ng ml-1, range 46-875 ng ml-1) were greater than those in the adrenaline group (median 33 ng ml-1, range 7-125 ng ml-1) (P = 0.001). All patients found the anaesthetic satisfactory. We conclude that intra articular/local anaesthesia is satisfactory for outpatient arthroscopic surgery, and that adrenaline should probably be added to bupivacaine before intra articular injection. PMID- 2248823 TI - An unusual complication of brachial plexus sheath cannulation. AB - A 20-gauge cannula placed via an interscalene approach in the left brachial plexus sheath of a healthy 18-yr-old male was used inadvertently for injection of 20 ml of antibiotic solution, despite clear labelling of the cannula and painful protest from the patient. The patient suffered no neurological sequelae. The treatment, possible causes and steps to avoid similar incidents are described. PMID- 2248824 TI - Intraventricular diamorphine via an Ommaya shunt for intractable cancer pain. AB - We describe two patients in whom diamorphine was administered into the intraventricular space via an Ommaya reservoir, producing excellent pain relief. The use of this technique for long term administration of analgesia is reviewed. PMID- 2248825 TI - Acute pulmonary oedema following administration of ornithine-8-vasopressin. AB - We report the case of a patient who developed acute pulmonary oedema following a short and uneventful surgical procedure. Among the differential diagnoses, the role of ornithine-8-vasopressin is emphasized. PMID- 2248826 TI - Comparison of pulse oximeters: accuracy at low arterial pressure in volunteers. AB - A laboratory model was developed of limb hypoperfusion in volunteers, using parital occlusion of the brachial artery with consequent reduction in radial artery pulse pressure. This was used to compare the function of 13 pulse oximeters and the effect of reduced pulse pressure and mild hypoxia on these devices. With the exception of one device, all the pulse oximeters studied demonstrated similar accuracies at pulse pressures exceeding 20 mm Hg. There were however, significant differences between several of the pulse oximeters in both ability to display readings and accuracy of readings displayed when brachial artery occlusion reduced radial artery pulse pressures equal to or less than 20 mm Hg. PMID- 2248827 TI - Non-invasive monitoring of finger arterial pressure in patients with Raynaud's phenomenon: effects of exposure to cold. AB - We studied the effects of exposure to cold on finger arterial pressure (FAP) measured by a finger arterial pressure monitor in 15 patients with Raynaud's phenomenon and in 15 healthy volunteers. The cold exposure induced vasoconstriction of the peripheral vascular bed as judged by the plethysmograph of a pulse oximeter and had marked effects on FAP values compared with upper arm arterial pressure. Immediately after the cold exposure, FAP decreased significantly (P less than or equal to 0.01) in both groups. However, during the subsequent 20 min, FAP values increased in relation to upper arm pressure. Finally, FAP values were greater than upper arm pressure in the control individuals, but not in patients with Raynaud's phenomenon. These results have implications for non-invasive monitoring of arterial pressure by the finger pressure device. Clinically, significant problems may arise in the monitoring of FAP in patients with a systemic connective tissue disease affecting peripheral circulation. PMID- 2248828 TI - Effect of motion artefact on pulse oximeters: evaluation of four instruments and finger probes. AB - The ability of the Ohmeda 3700, Nellcor N200, Datex Satlite Plus and Simed S100 pulse oximeters to detect induced hypoxaemia in the presence of motion artefact was assessed, under conditions of controlled vibration using an industrial vibration facility. Vibration at 4 Hz and 8 Hz induced increases in detection time for hypoxaemia and spurious decreases in the displayed SaO2 in some of the oximeters tested. Finger-dependent differences in oximeter performance and pulse rate registration were noted especially in those oximeters without ECG linkage (Ohmeda 3700 and Simed S100). Subsequently, eight different pulse oximeter finger probes were assessed for those characteristics that may predispose to motion artefact. There were marked differences in the mass of the probes, the forces exerted on the test finger and in the force required to displace the probes from the subject's finger. Differences in both the microprocessor programmes and the physical characteristics of the finger probes may explain the observed differences in function. Similar studies should form part of the standard evaluation of new pulse oximeters. PMID- 2248829 TI - Proceedings of the Anaesthetic Research Society, Nottingham meeting. July 6-7, 1990. Abstracts. PMID- 2248830 TI - Regional anaesthesia in porphyria. PMID- 2248831 TI - Surveillance and safety. PMID- 2248832 TI - A user-friendly disconnection alarm. PMID- 2248833 TI - IV infusions of morphine and regional analgesia by extradural block. PMID- 2248834 TI - Omeprazole--a useful new agent? PMID- 2248835 TI - Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane. AB - Eight volunteers inhaled isoflurane in concentrations of 0.1, 0.2 and 0.4 MAC, and 100% oxygen as control in separate sessions more than 1 week apart. When the end-expiratory isoflurane concentration was stable, response to verbal commands was tested, and the subjects were read 30 words in two lists. Response to the commands was impaired at 0.1 MAC in three subjects and lost at 0.2 MAC in two subjects. No subject responded at 0.4 MAC. When the subjects were questioned 1 h after exposure, memory of response to commands was lost also at these concentrations. Frequently, those who responded to the command "open your eyes" failed to remember having done so; non-responders remembered nothing. At the time of that test, at 0.4 MAC, five of eight subjects had no eyelash reflex. Both recall and recognition of neutral words was lost at 0.2 MAC and greater, but the effect of attention was demonstrated by the memory of a "shock" word by four of eight subjects at 0.2 MAC. PMID- 2248836 TI - Effect of oral omeprazole on intragastric pH and volume in women undergoing elective caesarean section. AB - We have studied in obstetric patients the efficacy of omeprazole in increasing intragastric pH to more than 2.5 and reducing volume to less than 25 ml. Omeprazole 40 mg was given orally the night before and again on the morning of surgery to 30 Asian women scheduled to undergo elective Caesarean section. After induction of anaesthesia, a gastric tube was inserted and intragastric contents aspirated. Volume and pH were recorded and measurements were repeated on completion of surgery. The median (range) volume was 2 (1-13) ml before surgery and 4 (0-14) ml at the end of surgery. There was insufficient volume to measure pH in all patients. The median (range) pH was 6.7 (4.6-7.4) before surgery in 20 patients and 6.6 (4.6-7.8) at the end of surgery in 28 patients. No adverse drug reactions were noted in mothers or neonates. Omeprazole 40 mg orally twice before elective Caesarean section appeared to be effective in reducing intragastric volume and acidity to acceptable values. PMID- 2248837 TI - Diclofenac for day-care arthroscopy surgery: comparison with a standard opioid therapy. AB - Sixty unpremedicated patients presenting for day-care arthroscopy surgery were allocated randomly to receive diclofenac 1 mg kg-1 i.m., fentanyl 1 microgram kg 1 i.v. or no analgesic during the course of anaesthesia. Patients receiving fentanyl had slightly, although not significantly prolonged recovery times. Patients receiving diclofenac had significantly improved postoperative visual analogue pain scores compared with patients receiving placebo medication (P less than 0.05). With fentanyl, pain scores were reduced also, but the effect was not statistically significant. Both fentanyl and diclofenac produced significant reduction in postoperative analgesic requirements (P less than 0.05). We conclude that diclofenac 1 mg kg-1 i.m. was an effective analgesic for arthroscopic procedures on the knee and is a useful alternative to opioids for day-care patients. PMID- 2248838 TI - Effect of indomethacin on pain relief after thoracotomy. AB - The effect of indomethacin on postoperative pain was studied in 60 adult patients undergoing thoracotomy in a prospective, randomized, double-blind manner. Patients receiving indomethacin required significantly less opioid after operation and had significantly lower pain scores compared with the control group. Pain on movement and on coughing were reduced also. No major adverse effects were encountered. PMID- 2248839 TI - Preanaesthetic medication with clonidine. AB - The purpose of this study was to evaluate oral clonidine in a dose of 0.3 mg as a routine premedicant. Sixty-nine normotensive female patients were studied in a randomized double-blind investigation in which clonidine was compared with an inert treatment. Clonidine produced a significant reduction in anxiety (P less than 0.05) and sedation and a reduction in the sleep dose of methohexitone (P less than 0.05). Tachycardia in response to intubation was attenuated by clonidine (P less than 0.05). However, the magnitude of the increase in arterial pressure after intubation was not affected. Intraoperative and postoperative hypotension were common after premedication with clonidine 0.3 mg and caution is urged in its use as a premedicant. PMID- 2248840 TI - Quantitative assessment of extradural bupivacaine analgesia. AB - Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection. PMID- 2248841 TI - Onset phase of spinal bupivacaine analgesia assessed quantitatively by laser stimulation. AB - Analgesia was assessed quantitatively at various dermatomes (C7, T8, T10, T12, L1, L3, S1) for the first 30 min after subarachnoid administration of 0.5% bupivacaine 3.5 ml. Stimulation with 10 needles and laser stimulation could evoke pain in dermatomes with adequate analgesia to single needle stimulation. Analgesia was assessed by thresholds (sensory and pain) and by pain-related brain potentials (amplitude and latency) to laser stimulation. Little analgesia was found at T10, but it increased gradually towards caudal segments. The dermatome related to the site of the injection (L3) was not blocked to a greater extent than the surrounding dermatomes. Conduction time (the latency of the evoked brain potential) was increased relatively more from the S1 dermatome compared with L1. PMID- 2248842 TI - Effects of 2% lignocaine on somatosensory evoked potentials recorded in the extradural space. AB - We have studied the effects of extradural administration of 2% lignocaine at the L3-4 interspace on somatosensory evoked potentials recorded in the cervical extradural space before corrective surgery for idiopathic adolescent scoliosis. Eight patients in whom the equivalent volume of 0.9% sodium chloride solution was administered into the lumbar extradural space acted as a control group. Lignocaine 2% resulted in a decrease in overall amplitude, but its main effect was a significant decrease in the amplitude of the second and third peaks, suggesting an action on the dorsal columns of the spinal cord. A significant increase in latency was found in both the lignocaine and sodium chloride groups. We conclude that the use of extradural 2% lignocaine in patients undergoing scoliosis surgery may interfere with the intraoperative monitoring of somatosensory evoked potentials. PMID- 2248843 TI - Comparison of four local extradural anaesthetic solutions for elective caesarean section. AB - We have examined a combination of two local anaesthetics to see if the resultant solution is superior to the agents individually. This study shows that a mixture of bupivacaine and lignocaine provided an excellent alternative to bupivacaine alone, and was superior to 2% lignocaine with adrenaline for elective Caesarean section. By reducing the dose of bupivacaine used, the combination may reduce the risk of cardiotoxicity. PMID- 2248844 TI - Pharmacokinetics of propofol in children. AB - The pharmacokinetics of propofol were studied in 12 healthy Chinese children, aged 4-12 yr, undergoing circumcision under inhalation anaesthesia. All patients received a single i.v. bolus dose of propofol 2.5 mg kg-1 and blood concentrations of propofol over the subsequent 24 h were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistent with a three-compartment model with a mean (SEM) elimination half-life of 209 (29) min and total body clearance of 40.4 (3.6) ml min-1 kg-1. The mean (SEM) apparent volume of distribution at steady state was 5.0 (2.7) litre kg-1 and volume of the central compartment was 0.6 (0.1) litre kg-1. The mean (SEM) ratio of k12:k21 was 1.4 (0.2), suggesting that, after injection of a single bolus dose in children, propofol is distributed rapidly to the shallow compartment. The mean ratio of k31:k10 suggests that lipophilicity constrains return of the drug to the central compartment. PMID- 2248845 TI - Pharmacokinetics of atracurium during continuous infusion. AB - The pharmacokinetics of atracurium were investigated by a model-independent method during continuous infusion under propofol anaesthesia. Following an intubating dose of suxamethonium, atracurium was infused according to a predetermined profile which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration when equilibrium between the biophase and plasma had occurred. Atracurium was infused for the first 1 h to maintain a target steady state plasma concentration of 1.0 microgram ml-1. Thereafter, the target plasma concentration was adjusted to maintain 90% muscle paralysis. The maintenance infusion rate required to maintain 90% paralysis was 4.25 (SD) 1.11 micrograms kg-1 min-1, with an estimated steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90) of 1.13 (0.24) microgram ml-1. The clearances of atracurium, estimated by the constant infusion rate required to maintain the steady state plasma concentration, at 50-60 min and during estimation of Cpss90 were 3.8 (1.0) and 3.9 (1.1) ml kg-1 min-1 (ns), respectively. The volume of distribution at steady state of atracurium after 1 h of infusion, calculated using the clearance and the area under the plasma concentration-time curve to 1 h, was 130 (50) ml kg-1. These estimates of the pharmacokinetic parameters of atracurium are markedly different from those derived from pharmacokinetic analysis of single bolus dose data. Normalization of the pharmacokinetic parameter estimates by lean body mass decreased interpatient variability and improved precision in comparison with the un-weighted data and normalization by total body weight. PMID- 2248846 TI - Pharmacodynamics of atracurium during propofol, thiopentone and opioid anaesthesia. AB - We have assessed in 20 patients the accuracy and precision of an infusion profile for atracurium, which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration, when equilibrium between the biophase and plasma had occurred. Muscle paralysis was stable after 20 min, with a mean absolute drift in muscle paralysis in the succeeding 40 min of 0.13 (SD 0.07)% T1/Tc (height of first twitch/height of control twitch) per min. The plasma samples after 30 min, which were assessed empirically as being in equilibrium with the biophase, had an overall mean bias of 8.0 (SEM 3.7)% (P less than 0.05) and an overall mean absolute prediction error of 16.4 (SEM 2.5)% from the target steady state concentration being delivered by the infusion. The profile was then used to estimate the steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90), by manually adjusting the delivered target concentration of the infusion until muscle paralysis was stable at 88-92% inhibition of T1/Tc for 15-20 min, with three plasma samples taken over the next 10 min. Measurements were completed within 60-90 min. The mean Cpss90 of atracurium with propofol was 1.039 (SD 0.224) microgram ml-1 (n = 10), with thiopentone 1.334 (0.378) microgram ml-1 (n = 10), and with opioid anaesthesia 0.915 (0.221) microgram ml-1 (n = 10). These differences in the Cpss90 explain some of the variability in response which occurs with neuromuscular blocking drugs. The technique enables the Cpss90 of a myoneural blocker to be determined by a simple model-independent method. PMID- 2248847 TI - Late postoperative episodic and constant hypoxaemia and associated ECG abnormalities. AB - Twenty-two patients without cardiopulmonary disease and undergoing elective major abdominal surgery were monitored continuously with a Holter tape recorder and a pulse oximeter on one night before operation and the first two nights after operation (23:00 to 07:00), without oxygen therapy. Mean heart rate increased 16 beat min-1 (P less than 0.001) and mean oxygen saturation (SaO2) decreased 2.6% (P less than 0.001) after operation. Episodic oxygen desaturation to less than 80% occurred in four patients before operation, but in 13 patients after operation (P less than 0.05). ECG abnormalities were observed in 10 patients before operation and in 16 patients after operation (ns). Individual maximum ST depression was more pronounced after than before operation (P less than 0.05). Episodic desaturation was related closely to tachycardia in six patients before operation and one patient after operation; before operation to atrioventricular block in one patient, and after operation to ST depression in two patients. Mean SaO2 on the second night after operation correlated with total dose of opioid for pain relief (rs = -0.48; P less than 0.05), and postoperative decrease in SaO2 correlated with postoperative increase in heart rate (rs = -0.43; P less than 0.05). No patient had postoperative cardiac complications indicating treatment. PMID- 2248848 TI - Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? AB - Excised muscles from patients with myotonia or periodic paralysis were subjected to the in vitro contracture test for susceptibility to malignant hyperthermia (MH). In a group of 44 patients, this standard test gave four positive, 10 equivocal and 30 negative results. The results for 27 control muscles from normal subjects were negative. When the test was performed with less than normal concentrations of contracture-triggering substances (caffeine less than or equal to 2 mmol litre-1, less than or equal to 2% halothane), 70% of the muscles from the patients and only 15% of the controls responded with small contractures (less than 0.2 g). These results should not be taken to indicate that the patients have the genetic trait for MH. The positive and equivocal test results, in addition to the slight contractures, may be accounted for by the electrical after-activity in the cases of pure myotonia, and by increased resting myoplasmic [Ca2+] in myotonic dystrophy. This shows that the in vitro contracture test lacks specificity. PMID- 2248849 TI - Effect of isoflurane on the canine hepatic circulation and hepatic oxygen balance. AB - We have studied the effects of increasing concentrations of isoflurane (1%, 1.5% and 2%) on the hepatic circulation and the oxygen supply and demand of the liver in six barbiturate-anaesthetized greyhounds. Following laparotomy, the hepatic arterial and portal venous blood flows were measured continuously using electromagnetic flow probes, and mean arterial pressure and cardiac output were measured as appropriate. Cardiac output was maintained while mean arterial pressure and systemic vascular resistance decreased in a dose dependent manner. Hepatic arterial and total liver blood flows and oxygen supplies decreased significantly at all isoflurane concentrations. Portal venous blood flow and portal venous oxygen supply did not decrease significantly until the concentration of isoflurane was increased to 2% and 1.5%, respectively. Hepatic oxygen consumption was reduced with 2% isoflurane (P less than 0.05), but this was insufficient to offset the reduction in hepatic oxygen supply and resulted in an increased extraction of oxygen by the liver. PMID- 2248850 TI - Nitrous oxide antagonizes CNS stimulation by laudanosine in mice. AB - We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine. PMID- 2248851 TI - Sinus arrest induced by trivial nasal stimulation during alfentanil-nitrous oxide anaesthesia. AB - A case is reported of bradycardia and sinus arrest induced by insertion of a nasal temperature probe. Other possible causes of bradycardia and sinus arrest under anaesthesia are reviewed briefly. Evidence for the neurological basis of a nasocardiac reflex, similar to the oculocardiac reflex, is presented. A minor, trivial stimulus may elicit this reflex. PMID- 2248852 TI - 7th nerve palsy after extradural blood patch. AB - We describe a patient who developed a 7th cranial nerve palsy following an extradural blood patch; full recovery followed. The likely aetiology is discussed. PMID- 2248853 TI - Anaesthetic hazards of aortocaval fistula. AB - A 66-yr-old man was anaesthetized for repair of a suspected ruptured aortic aneurysm. He became deeply cyanosed and suffered two episodes of asystole as the surgeons entered the abdomen. After the aorta was cross-clamped his condition improved markedly and no further problems ensued. Surgical exploration demonstrated intact aneurysms of the aorta and left iliac artery, the former containing a 3-4 cm long aortocaval fistula. The aneurysms and fistula were repaired and his further course was uncomplicated. Potential causes for the cyanosis and cardiac arrest in this patient are discussed. PMID- 2248854 TI - IV fluids during surgery. AB - During an attempt to measure renal function during operation in six patients undergoing major abdominal surgery involving intestinal resection and blood loss in excess of 300 ml, it became apparent that the conventional recommendation for i.v. crystalloid fluid of 5-10 ml kg-1 h-1 was not sufficient to maintain cardiovascular stability and urine output, but a volume of 15 ml kg-1 h-1, given to a subsequent six patients, was adequate. Administration of low sodium (glucose) solutions also produced biochemical abnormalities of a severity not documented previously. A survey of the published literature on volumes of crystalloid fluids used supports the contention that, during major surgery, crystalloid requirements may be of the order of 10-15 ml kg-1 h-1 rather than 5 10 ml kg-1 h-1. PMID- 2248855 TI - Extradurals and shivering. PMID- 2248856 TI - [Plasma beta-endorphin levels in silent or symptomatic myocardial ischemia]. AB - The role of increased beta-endorphin activity in patients with silent myocardial ischemia has been postulated. To further investigate this hypothesis, 13 patients with silent myocardial ischemia (A) and 10 patients with exercise-induced angina (B) were studied. To be entered in groups A and B patients had to fulfill the following criteria: occurrence or not of anginal pain, according to history and clinical data, during a positive exercise ECG and associated imaging of reversible perfusion defect at thallium-201 scintigraphy. Basal plasma beta endorphin levels showed significantly (p less than 0.05) higher values in group A as compared to group B. At the end of an exercise stress test, plasma beta endorphin levels were measured in 9 patients from group A and in 7 from group B. Post-exercise beta-endorphin levels showed a mild increase in group A, but increased significantly in group B (p less than 0.02). The patients with silent or symptomatic myocardial ischemia were quite well-matched with regard to age, sex, number and localization of obstructed coronary vessels, positive exercise ECG and imaging of reversible perfusion defect at thallium-201 scintigraphy. The higher basal plasma beta-endorphin levels in patients with painless ischemia, compared to symptomatic patients, suggested that endogenous opioid peptides play a role in the perception of anginal pain during myocardial ischemia. The fact that post-exercise plasma beta-endorphin levels increased in symptomatic patients but remained unchanged in patients with silent myocardial ischemia does not lead to conclusive considerations. PMID- 2248857 TI - [Monitored and random arterial blood pressure as prediction of biological risk. Comparison with domiciliary self-measurement]. AB - The approach to the hypertensive patient is still a subject of debate. The use of new measurement methods permits us to obtain more exact blood pressure values which represent an index of cardiovascular condition. We also demonstrated that non-invasive monitoring and self-measurement at home consent better management of hypertension. PMID- 2248858 TI - [Class IgA antigliadin antibodies and monitoring of compliance to gluten-free diet in celiac disease]. AB - Antibodies to gliadin (AGA), detected by ELISA, were found in the sera of 37 (88%) of 42 patients with untreated adult celiac disease. IgG class AGA showed a higher sensitivity for the diagnosis of celiac disease than IgA AGA, but, while IgA AGA had a specificity of 100% for celiac disease, false positives of IgG class were present in 19% of 37 patients with ulcerative colitis and in 27% of 26 patients with Crohn's disease. Twenty-eight out of our 42 adult celiac patients were tested after 6-12 months of gluten free diet: IgG AGA persisted in 43% of them showing antibody titres lower than those observed in untreated celiac disease. IgA AGA became negative after gluten withdrawal and there was regrowth of jejunal villi in all but 2 adult celiac patients (7%), who continued to present IgA AGA positivity and subtotal villous atrophy. These 2 patients did not comply to the gluten free diet. Our study confirms the specificity of IgA AGA for untreated celiac disease and emphasizes their usefulness in monitoring the compliance with gluten free diet in adult celiac disease. PMID- 2248859 TI - [Factor VII and cardiovascular risk in obese subjects]. AB - We investigated whether or not obesity is related to increased factor VII activity. We studied 70 obese subjects (aged 25 to 50 years, 25 males and 45 females, body mass index (BMI): mean +/- SD = 32.44 +/- 5.44) and 33 non-obese subjects (aged 25 to 50 years, 12 males and 21 females, BMI: mean +/- SD = 21.80 +/- 1.70). None of them were smokers or affected by hyperlipidemia, diabetes mellitus, impaired glucose tolerance or arterial hypertension. Factor VII activity was measured by the coagulometric method. We found higher factor VII activity in obese subjects (115.74 +/- 26.10%) than in healthy subjects (98.55 +/ 23.49%, p less than 0.005). Increased factor VII levels could determine a thrombophilic state involved in the genesis of cardiovascular accidents in obesity. PMID- 2248860 TI - [Infection and blood filterability]. AB - Some markers of inflammation were monitored, and whole blood filterability was measured using a low shear positive pressure nuclepore filtration system in 21 patients at the onset of an acute bacterial infection and again after full clinical recovery 4 weeks later and compared to the filterability of 40 matched healthy controls. Impairments in whole blood filterability persisted even after convalescence. PMID- 2248861 TI - [Sudden cardiac death in subjects with healthy heart. Role of heart-mind interactions]. AB - The Authors report the significant progress that has been made in the past few decades in defining the connections between the central nervous system and the cardiovascular system and the mechanisms by which neuroadrenergic influences over cardiac function can lead to heart disease. Moreover, the question of sudden cardiac death, particularly in individuals without a prior history of clinical heart disease, is analysed in the light of present knowledge concerning the deleterious effects on cardiac electrophysiologic properties of psychosocial and behavioural factors. PMID- 2248862 TI - [Clinical significance of serum bile acid determination in liver diseases]. AB - The recent availability of radioimmunological and enzymatic kits to measure serum bile acids (SBA) has allowed diffusion of this laboratory test. The aim of this paper is to provide an assessment of diagnostic and prognostic significance of SBA in liver cirrhosis, on the basis of the most recent data available to us. Measurement of these substances in serum does not appear to be very useful either in screening or in differential diagnosis of liver disorders, since it seems unable to provide further information with respect to commonly used parameters. On the contrary, SBA show a remarkable predictive value both in chronic active hepatitis and in liver cirrhosis. SBA measurement may therefore become a useful tool in planning the therapeutic approach to these hepatic diseases. PMID- 2248863 TI - [Surgical risks for cirrhotic patients]. AB - Evaluation of the surgical risk in cirrhotic patients undergoing emergency operations must take into account potential anesthesia-related problems, the specific type of operation, and altered liver function. Therefore, (a) the generic surgical risk, (b) the specific surgical risk and (c) the anesthetic risk, must be distinguished. The factors which affect the generic risk are the conditions which can worsen pre-existing liver failure (e.g. cardiopulmonary disease, area of surgical intervention, stage of liver cirrhosis). Splanchnic reflexes as well as lower venous return to the heart are the potential factors which may lead to reduced hepatic blood perfusion and, therefore, represent the specific surgical risk. The anesthetic risk is due to negative interference with the splanchnic circulation by both artificial ventilation and direct pharmacologic vasoconstrictor effects. Finally, the possibility that the patient is positive for HBV or HIV markers must be considered in order to carry out the necessary measures to avoid direct contact with the blood. PMID- 2248864 TI - [Ethical duties of medicine]. PMID- 2248865 TI - [Serum osteocalcin in hyperthyroidism]. AB - Several bone metabolism biochemical parameters were measured to evaluate the increased serum osteocalcin (sBGP) in hyperthyroidism. Twenty patients (19 women and 1 man, aged 22-69) and 20 age and sex-matched healthy subjects were examined. The following serum measurements were performed: calcium, phosphate, mid-molecule PTH, calcitonin, 25OH vitD, alkaline phosphatase, total and free thyroid hormones; urinary excretion of calcium, hydroxyproline and creatinine was also measured. The results (mean +/- standard error) show significant increases of sBGP (16.4 +/- 1.02 ng/mL; p less than 0.001), serum calcium (10.1 +/- 0.1 mg/dL; p less than 0.001), alkaline phosphatase (144.0 +/- 11.7 UI/L; p less than 0.001), urinary calcium (315.6 +/- 48.5 mg/g urinary creatinine; p less than 0.001) and hydroxyproline (43.0 +/- 6.1 mg/g urinary creatinine; p less than 0.001). A significant correlation between total and free thyroid hormones and sBGP was found. Accelerated bone turnover in hyperthyroid patients is therefore confirmed: both osteoclastic bone resorption, as suggested by increased serum and urinary calcium and urinary hydroxyproline, and osteoblastic bone formation, as suggested by increased serum osteocalcin and alkaline phosphatase, are stimulated. PMID- 2248866 TI - [Pancreatic pain and splanchnic neurotomy]. PMID- 2248867 TI - [A modification of the Sweet-Allen simple reconstruction technique after total gastrectomy]. AB - The Authors report their personal modification of Sweet-Allen's esophago-jejunal reconstruction after total gastrectomy. In their opinion, it enables to combine the advantages of the omega-shaped loop (easier and faster surgical technique, reduced postoperative morbidity) with those typical of the Roux-en-Y loop, that is complete elimination of biliary reflux, leading to better long term functional outcome and quality of life for the totally gastrectomized patient. PMID- 2248869 TI - [Complications of the anterior resection of the rectum]. AB - The Authors report their experience, referred to the last 10 years (1980-1989), concerning 169 cases of anterior resection of the rectum. Manual and mechanical anastomoses were performed in 83 and 86 cases, respectively. Immediate and long term complications are evaluated considering the type of anastomosis used, while results are correlated to the stage of the tumor. PMID- 2248868 TI - [Role of screening as an index of predictability in the early diagnosis of nonpalpable lesions of the breast]. AB - The Authors, on the basis of their personal experience and supported by more significative data from the international literature, underline the validity of the screening in detecting non palpable lesions of the breast. They conclude by asserting that mortality for breast cancer may be further reduced if more and more women undergo screening programmes. PMID- 2248870 TI - [C. pylori colonization of the mucosa in patients with chronic ulcerative and non ulcerative gastropathies]. AB - C. pyloridis colonization was investigated in a selected group of 58 patients with upper gastrointestinal disorders submitted to endoscopy and biopsy. The following results were registered. C. pyloridis was isolated in 14 out of 18 cases of active chronic gastritis, in 15 out of 24 cases of non active chronic gastritis, and 7 out of 8 cases of antral ulceration. A negative finding was registered in 8 patients whose gastric mucosa was normal. Therefore, the Authors consider as valid the etiopathogenetic correlation between C. pyloridis and ulcerative or non-ulcerative chronic gastric diseases, suggested by others. PMID- 2248871 TI - [Total gastrectomy for cancer: personal experience with reconstruction of the alimentary tract]. AB - Nineteen patients with total gastrectomy for neoplastic diseases were followed up from twelve to thirty months. Three different surgical reconstructive procedures were employed. Results are discussed and compared with those of the recent literature. PMID- 2248872 TI - [Involvement of the inferior vena cava in hepatic and renal neoformations]. AB - The Authors report their experience in 4 cases of involvement of the inferior vena cava by hepatic and renal neoplastic and non neoplastic lesions. They describe the modern diagnostic technics and consider the surgical approaches in such cases. PMID- 2248873 TI - [Symptomatologic and surgical definition of functioning parathyroid carcinoma]. AB - Hyperparathyroidism due to parathyroid carcinoma is rare. The natural history of this neoplastic disease is poorly understood for the extremely small number of cases reported in literature. The Authors observed three cases and discuss the clinical features illustrating how to recognize and treat this neoplasia. PMID- 2248874 TI - [Unilateral polycystic renal dysplasia]. AB - The Authors report two cases of unilateral multicystic kidney dysplasia comparing the etiopathogenetic and clinical characteristics with those of polycystic kidney disease. They conclude with some considerations on the current therapeutic trend in these cases. PMID- 2248875 TI - [Anatomo-surgical study on a new technique of nephropexy]. AB - The Authors carried an autoptic study on ten cadavers in order to clarify and if necessary modify some aspects of the nephropexy technique which was modified and improved by them. Two main conclusions are reported. First, the approach is better obtained by a prolonged incision to the twelfth rib. Second, possible damage to the diaphragm and to the lung are avoided with this technique. Furthermore, the study provides information about the preparation and suture of the capsule. PMID- 2248876 TI - Diarrhoeal diseases control programme. Global activities, 1988-1989. PMID- 2248877 TI - Ethics and epidemiology. PMID- 2248878 TI - Veterinary public health. Poultry and egg salmonellosis. PMID- 2248879 TI - Rabies in a llama. PMID- 2248880 TI - Alcohol abuse. Alcohol-related mortality and potential years of life lost, 1987. PMID- 2248881 TI - Veterinary public health. New approaches in prevention of pathogen colonization in the intestinal tract of food animals. PMID- 2248882 TI - Practical means to reduce Salmonella cross-contamination during slaughtering and processing of animals. PMID- 2248883 TI - Acquired immunodeficiency syndrome (AIDS). HIV infections, 1989. PMID- 2248884 TI - Antigenic analysis of recent influenza virus isolates. PMID- 2248885 TI - Nutrition. Iodine deficiency and its effects in Europe. PMID- 2248886 TI - Radiobiological studies in the naevoid basal cell carcinoma syndrome. AB - The naevoid basal cell carcinoma syndrome is described in a 43-year-old male. The response of dividing fibroblasts from this patient to the lethal effects of ionizing radiation was indistinguishable from that of a normal control: mean inactivation dose (D) = 1.74 Gy and 1.68 Gy, respectively. However, these cells were defective in the repair of potentially lethal damage (D = 2.36 Gy and 3.26 Gy, respectively). The response to radiation of Go T lymphocytes derived from the patient was similar to that of the control. The frequency of mutant circulating T lymphocytes resistant to 6-thioguanine was 17 x 10(-6) which was elevated when compared with age-matched controls. These results suggest an abnormality in the response of the fibroblasts to ionizing radiation damage. PMID- 2248887 TI - Induction of ornithine decarboxylase following sellotape stripping in normal and psoriatic skin. AB - Ornithine decarboxylase (ODC) was measured in the epidermis of healthy volunteers and the uninvolved skin of psoriatic patients at various times after sellotape stripping. Basal levels were less than 1 pmol/min/mg protein. Activity peaked to a maximum of 86 pmol/min/mg protein after 8 h; this was followed by an abrupt decline to a lower level which remained relatively constant for at least 36 h. No difference was seen between the response of controls and psoriatic patients. Pretreatment with topical corticosteroids reduced peak ODC levels to about one half, but oral indomethacin had no effect. PMID- 2248888 TI - The significance of Leu 8 negative T cells in lymphoid skin infiltrates: malignant transformation, selective homing or T-cell activation? AB - The expression of Leu 8 was studied on skin biopsies from a large group of patients with benign and malignant skin disorders and correlated with the expression of T-cell differentiation antigens and activation markers. The effect of in vitro stimulation of peripheral blood T cells and T-cell subsets on the expression of Leu 8 antigen was also determined. In all the skin diseases studied an inverse relationship was found between the proportions of cells expressing Leu 8 and HLA-DR. A deficiency of Leu 8 positive cells was not specific for mycosis fungoides, but was also found in several reactive dermatoses. Stimulation of peripheral blood cells with phytohaemagglutinin (PHA), concanavalin A (Con A), and anti-CD3-PMA resulted in a considerable decrease of Leu 8 antigen expression on day 3 in both CD4+ and CD8+ T cells. These data suggest that the low proportion of Leu 8+ T cells in mycosis fungoides and several reactive skin disorders is not related to malignant transformation or selective homing of Leu 8 T cells, but probably results from local T-cell activation. PMID- 2248889 TI - Immediate contact reactions to chemicals in the fragrance mix and a study of the quenching action of eugenol. AB - In this study, the nature of non-immune immediate contact reactions (NIICR) produced by cinnamic aldehyde, benzoic acid and sorbic acid were investigated, with particular interest in the 'quenching' ability of eugenol. Three groups of human subjects were studied, and the guinea-pig ear was also used as a model of NIICR. Cinnamic aldehyde, benzoic acid and sorbic acid were all able to produce NIICR in the majority of subjects studied. There was a strong correlation between the susceptibility of each subject to each urticant, but no correlation between the susceptibility to NIICR and age, atopic status or tanning ability. Eugenol caused a reduction in NIICR induced by all three urticants. This 'quenching' effect was apparent even when the eugenol was applied up to 60 min prior to application of cinnamic aldehyde, and its effect was not eliminated by washing. In the guinea-pig-ear model, ear thickening was induced by all three urticants, and this response was inhibited by eugenol. PMID- 2248890 TI - Cutaneous sodium lauryl sulphate irritation potential: age and regional variability. AB - To investigate differences in response to irritation according to age and site seven young-adult and eight elderly females were exposed to 0.25% sodium lauryl sulphate (SLS) under patch-test occlusion for 24 h. Ten anatomical regions were tested: forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper back, thigh, and ankle. The skin responses were evaluated 24 h post-patch removal by visual scoring and by transepidermal water loss measurements (TEWL). Non-treated symmetrical anatomical regions served as controls. SLS induced a mild erythematous reaction on most anatomical regions except the palm and TEWL was significantly increased as compared with controls. The elderly group demonstrated significantly less susceptibility to SLS-induced irritation for most regions of the body as indicated by visual scores and TEWL measurements. In addition, evaluation of the stratum corneum water content following SLS irritation demonstrated lower responses in the old age group for most regions. The thigh had the highest reactivity and the palm the lowest, in both age groups. These data suggest that young adult skin is more sensitive to SLS than old skin and that SLS irritation varies considerably with respect to region. Moreover, objective TEWL measurements seem to be a better indicator of irritant susceptibility, especially in the elderly, than clinical evaluation by visual scoring. PMID- 2248891 TI - Conjunctival involvement in pemphigus vulgaris: a clinical, histopathological and immunofluorescence study. AB - Eleven patients with pemphigus vulgaris and with eye complaints had histopathological and direct immunofluorescence (DIF) studies on biopsies of their conjunctivae. In eight of the patients the ocular symptoms preceded the other manifestations of pemphigus. None of the 11 patients had any detectable conjunctival blisters or erosions. The conjunctivitis in three of the patients proved on histopathology and DIF to be a manifestation of pemphigus vulgaris. In the remaining patients, conjunctival hyperaemia with or without a mucoid discharge was observed, but there were no specific histopathological features, although one of them had a positive DIF. PMID- 2248892 TI - Cyclosporin A in combination with photochemotherapy (PUVA) in the treatment of psoriasis. AB - Forty patients with relapsing plaque psoriasis involving more than 20% body surface were treated either with cyclosporin A (CyA) plus PUVA or the retinoid etretinate plus PUVA (RePUVA). They initially received either CyA (2 weeks) or etretinate (1 week) alone and then PUVA was given concomitantly until complete remission. The patients were monitored over a period of 6 months and any relapse recorded. With each combined treatment regimen, CyA plus PUVA and RePUVA, the patients cleared within comparable periods of time (mean treatment period of 5.3 vs. 4.7 weeks after initiation of therapy and 3.3 vs. 3.7 weeks after initiation of PUVA). However, the cumulative UVA dose required for clearance (110.9 J/cm2 vs. 62.1 J/cm2 (P less than 0.05)) and the incidence of severe and early relapses were significantly higher in the CyA cohort. Within 6 months severe relapses had occurred in 58% of CyA plus PUVA but only in 15% of RePUVA-treated patients (P less than 0.001). This suggests that the CyA plus PUVA regimen as performed in this study is less effective than RePUVA. PMID- 2248893 TI - A case of T-cell lymphoma associated with panniculitis, progressive pancytopenia and hyperbilirubinaemia. PMID- 2248894 TI - Pachyonychia congenita complicated by hidradenitis suppurativa: a family study. AB - A family is described in which five of the six members with the Jackson-Lawler type of pachyonychia congenita also had varying degrees of hidradenitis suppurativa. We suggest an association between this type of pachyonychia congenita and hidradenitis suppurativa. PMID- 2248895 TI - Profound digital collagen atrophy: a new cutaneous presentation of adrenal dependent Cushing's syndrome. AB - A 59-year-old Caucasian housewife presented with a 2-year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome. PMID- 2248896 TI - Proceedings of the 248th meeting of the Netherlands Society for Dermatology and Venereology. Groningen, 12 May 1990. Abstracts. PMID- 2248897 TI - Acantholytic lesions in the vagina. PMID- 2248898 TI - Persistent bite reactions responsive to photochemotherapy. PMID- 2248899 TI - Terrien's marginal degeneration: corneal topography. AB - Computer-assisted corneal topographic analysis was used to evaluate the corneal contour of four patients with Terrien's marginal degeneration. The corneal topography in these patients was characterized by flattening over the areas of peripheral thinning produced by the disorder. When thinning was restricted to the superior and/or inferior areas of the peripheral cornea, there was a relative steepening of the corneal surface approximately 90 degrees away from the midpoint of the thinned area. This resulted in high against-the-rule or oblique astigmatism characteristic of the disorder. This common pattern is attributable to the frequency with which the superior and/or inferior peripheral cornea is preferentially involved in Terrien's marginal degeneration. In some patients, the central corneal topography may remain relatively spherical if the area of thinning is small or if the disorder extends around the entire circumference of the cornea. PMID- 2248900 TI - Topographic changes that occur with 10-0 running suture removal following penetrating keratoplasty. AB - Twelve eyes undergoing penetrating keratoplasty with a double-running suture technique had corneal topographical analysis immediately before and one month after 10-0 suture removal. Substantial changes in astigmatism were evident following suture removal. Twenty five percent of eyes showed a decrease of 1 D, 33% of eyes showed a decrease of 3 D, 8.3% of eyes showed an increase of 1 D, 8.3% of eyes showed an increase of 2 D, 16.6% of eyes showed an increase of 3 D, and 8.3% of eyes showed an increase of 4 D of astigmatism following suture removal. The mean corneal astigmatism did not show a significant change from a mean of 5.3 D after suture removal. There was less individual variation of spherical corneal power following suture removal. Thirty three percent of eyes showed a decrease of 1 D, 33% of eyes showed a decrease of 2 D, 8.3% of eyes showed a decrease of 3 D, 18.3% of eyes showed an increase of 1 D, and 6.6% of eyes showed an increase of 2 D of spherical power following suture removal. The surface asymmetry index (SAI), a centrally weighted measure of corneal surface irregularity, decreased significantly (P less than 0.04) from a mean of 1.17 before suture removal to a mean of 0.93 after suture removal. These results suggest that surface irregularity may be decreased following the removal of a single running 10-0 nylon suture following penetrating keratoplasty. PMID- 2248901 TI - The corneal topography of epikeratophakia. AB - Epikeratophakia is a surgical technique initially developed for the correction of aphakia, and later adapted for the correction of keratoconus and myopia. The concurrent development of color-coded computerized corneal topography has greatly assisted in the evolution of epikeratophakia. Corneal topography has demonstrated the importance of both accurate centration of the epikeratophakia lenticle over the visual axis and the size of the optical zone on the final refractive results. Corneal topographic changes associated with correction of aphakia are primarily the result of steepening of the anterior radius of curvature of the cornea, in contrast to myopic correction which results in flattening of the anterior cornea. Correction of keratoconus results from a physical compression of the cone thereby flattening both the anterior and posterior radii of curvature. Preoperative topography in patients with keratoconus permits the precise position and extent of both regular and irregular astigmatism mation may assist in designing the optimal lenticle size and amount of graft decentration necessary to achieve the maximal surgical effect. Corneal topographic mapping has also been helpful in the management of postoperative astigmatism following epikeratophakia. Topography identifies the location and extent of both regular and irregular astigmatism which assists in planning of both surgical and nonsurgical intervention. Corneal topographic mapping has also been extremely helpful in the management of postoperative astigmatism following epikeratophakia. Topography identifies the location and extent of both regular and irregular astigmatism which assists in planning of both surgical and nonsurgical intervention. PMID- 2248902 TI - Lipid deposits posterior to impermeable intracorneal lenses in rhesus monkeys: clinical, histochemical, and ultrastructural studies. AB - Synthetic materials are being evaluated for their potential long-term use in corneal refractive surgery. Clinical and histopathologic studies were performed with polymethylmethacrylate (PMMA) and polysulfone intracorneal lenses in rhesus monkey eyes that were followed for up to 3 years. The 5 mm diameter lenses were placed in the deep posterior corneal stroma of four eyes. Fine, polychromatic crystalline deposits formed a layer posterior to the implants. Enucleated eyes had the corneas either frozen for histochemistry or fixed for electron microscopy. Special stains included oil red 0 and filipin on fresh frozen tissue. The cornea, with a PMMA intracorneal lens showed myriad crystalline aggregates in the deep corneal stroma behind the implant. These crystalline deposits stained positively with oil red 0 and with filipin indicating the presence of neutral fat as well as unesterified cholesterol. The polysulfone implant showed no evidence of crystalline deposits histologically but was surrounded by homogeneous aggregates that could represent nonspecific reaction to the lens material or protein deposits. Electron microscopy of all four corneas revealed dissolved lipid aggregates and laminated electron dense material that were most abundant posterior to the implant where the keratocytes appeared disintegrated. The PMMA lens appeared to induce lipid keratopathy. PMID- 2248903 TI - Barraquer lecture. Bernard E. McCarey, PhD. PMID- 2248904 TI - Stability of refraction during two years after myopic epikeratoplasty. AB - A series of 54 consecutive myopic epikeratoplasty procedures was performed by three surgeons between November 1986 and August 1987. To evaluate the stability of the myopic epikeratoplasty procedure, this study was limited to the 33 eyes that had data 24 months after surgery. One year after surgery, 68% (19/28 eyes) had 20/40 or better uncorrected visual acuity and after two years, 57% (17/30 eyes) had 20/40 or better uncorrected visual acuity. Significant loss of surgical effect (increasing myopia) did not occur during the first six postoperative months (r = 0.09, P = NS). This was due to the large amount of variability in spherical equivalent refraction during this interval. However significant regression was detected between 6 and 12 months after surgery (r = 0.27, F = 4.74, P = 0.03). Even though there was further reduction in variability from 12 to 24 months, significant regression was not found (r = 0.07, P = NS). This suggests stabilization of refraction by approximately 12 months for this population. PMID- 2248905 TI - Current status of refractive surgery with synthetic intracorneal lenses: Barraquer lecture. PMID- 2248906 TI - The importance of pupil size in optical quality measurements following radial keratotomy. AB - This review considers the importance of pupil size when specifying the optical quality or visual performance of eyes following radical keratotomy. The experimental evidence presented includes measurements both before and after radial keratotomy of the eye's: 1) corneal curvature; 2) optical aberrations; 3) modulation transfer function; 4) visual acuity as a function of test beam entry; and 5) disability glare. Together these five lines of evidence demonstrate that pupil size is a key factor influencing both the optical quality of the eye and visual performance. PMID- 2248907 TI - Delayed sterile keratitis following radial keratotomy requiring corneal transplantation for visual rehabilitation. AB - Delayed keratitis is an unusual complication of radial keratotomy surgery. A case of documented sterile keratitis involving four adjacent nasal incisions occurred 34 months following a 16-incision radial keratotomy procedure. Multiple cultures and biopsies failed to show a pathogen. The keratitis was confined to the incisional area without involvement of the intervening stroma. A penetrating keratoplasty was necessary to restore useful vision. Clinical and pathological studies documented delayed corneal wound healing. PMID- 2248908 TI - Minimal essential standards for reporting studies of refractive surgical procedures. PMID- 2248909 TI - Pressure patching after radial keratotomy using a sweatband. PMID- 2248910 TI - Defining the limits of radial keratotomy. PMID- 2248911 TI - Comparison of a computer-assisted laser pachometer with two ultrasonic pachometers in normal corneas. AB - A computer-assisted laser pachometer was compared with two ultrasonic pachometers for intra- and interobserver error. Two observers each performed two examinations at 11 predetermined locations on the corneas of six subjects. The laser pachometer was found to have intra- and interobserver errors comparable to both of the ultrasonic pachometers. By performing multiple examinations on three subjects, the laser pachometer was found to have an average standard deviation of +/- 0.012 mm. Unlike ultrasonic pachometers, the laser pachometer has the advantage of being a noncontact method of evaluating corneal thickness, and does not require topical anesthesia; the trauma and anesthesia might alter corneal thickness by inducing epithelial edema. The nasal cornea was found to be slightly thicker than the temporal cornea in most patients. Lid closure for three hours caused a consistent thickening (about 6.3%) of central and peripheral cornea. PMID- 2248912 TI - Combining refractive error and uncorrected visual acuity to assess the effectiveness of refractive corneal surgery. AB - Residual refractive error and uncorrected visual acuity are two frequently measures used to assess the effectiveness of refractive corneal surgery. Nordan and colleagues have suggested a Visual Function Index which combines these two measures in one quantitative measure. This article presents a Visual Function Score for radial keratotomy which includes a set of qualitative categories (excellent, good, fair, poor) and specifies the clinical values for refractive error and visual acuity in each category. There was substantial agreement among ophthalmologists who reviewed the category definitions, and we think that the Visual Function Score improves our ability to objectively assess surgical outcome. Application of the score to the Prospective Evaluation of Radial Keratotomy (PERK) Study data yielded closer agreement with refractive error results than with visual acuity values. The Visual Function Score lowered the classification of eyes that were hyperopic but had sufficient accommodation to overcome so that a high visual acuity result could be achieved. The inclusion of astigmatism values would be an important next step in the development of composite measures for the assessment of refractive surgery. In the future, a multifactorial index or score may be used to estimate the outcome of reported surgical procedures. PMID- 2248913 TI - Corneal flattening by shallow circular trephination in human eye bank eyes. AB - Recent reports documenting central keratometric changes after removal of failed epikeratoplasty lenticules, compared to preoperative keratometry measurements, suggest that the annular corneal wound alters corneal curvature. Central corneal steepening has also been reported following circular and hexagonal keratotomy. We performed standard epikeratoplasty trephination with a Hessburg-Barron suction trephine followed by a peripheral lamellar spreading keratotomy on seven human eye bank eyes to determine the effect of these incisions on corneal topography. In seven human eye bank eyes, the mean acute central keratometric flattening from the shallow trephine incision was 2.81 D (SD 2.28, P = .017), with no significant change in keratometry due to peripheral lamellar spreading (P = .916). Computerized numeric and three-dimensional graphic analysis of the keratographs demonstrated this central topographic flattening. Further studies are needed to investigate the reversibility of host corneal changes induced by epikeratoplasty procedures. PMID- 2248914 TI - Electron microscopic examination of prelathed, lyophilized tissue used for epikeratophakia in humans. AB - Morphologic changes secondary to cryolathing and lyophilization have been described in tissue lenses used for epikeratophakia. We report the electron microscopic findings of an aphakic tissue lens which could not be used because of sudden preoperative myocardial infarction of the patient. Scanning electron microscopy revealed the presence of three distinct zones (peripheral, intermediate, and central) on the stromal side of the lens. The surface of the central zone appeared to be the smoothest, as a consequence of the different angle of lathing. The Bowman's layer side of the tissue lens exhibited a uniform, smooth surface. Transmission electron microscopy revealed a largely normal collagenous structure of both stroma and Bowman's layer. Interfibrillary distances were within normal limits. Several giant stromal spaces of various dimensions filled with homogeneous material were observed. Variably preserved keratocytes were a regular finding among the lamellae. Our findings confirmed some of the structural changes previously observed in tissue lenses not used for epikeratophakia in humans. The limited size of a smooth central zone of the posterior surface could explain some postoperative complaints such as persistent glare phenomena, as well as prolonged visual rehabilitation time, especially in those cases where centration of the epi-lens onto the recipient cornea is not optimal. PMID- 2248915 TI - Epikeratophakia for the correction of myopia: lenticule design and related histopathological findings. AB - In spite of the numerous changes in surgical technique, epikeratophakia for the correction of myopia is still far from achieving optimal results. The removal rate of myopic lenticules is much higher than that of aphakic or keratoconus lenticules and has prompted the FDA to deny its approval to the industrial production of epi-lenses for the correction of myopia. We report a patient who underwent epikeratophakia for the correction of high myopia in his left eye and required removal of the lenticule because of unsatisfactory visual outcome. The histologic and electron microscopic examination of the removed lenticule revealed the presence of folds in both Bowman's layer and superficial stroma. These had been described in the past and related to the surgical technique used at that time; they were thought to be the cause of poor visual acuity n two patients, and had prompted, therefore, a change in surgical technique. Our findings suggest that the present lenticule design could be responsible for the presence of folds and the consequent poor visual result. PMID- 2248917 TI - Corneal steepening in human eye bank eyes by combined hexagonal and transverse keratotomy. AB - An interrupted 5 mm diameter hexagonal keratotomy was modified to include six paracentral transverse incisions to augment the central corneal steepening. This combined modified-hexagonal and transverse (or hexagonal-transverse) keratotomy was performed on human eye bank eyes to an estimated 85% corneal depth yielding a mean of 7.50 +/- 1.69 diopter increase in central keratometric power (P less than .001); this finding was confirmed by keratography. These results encourage further studies of this procedure and its potential to surgically correct mild amounts of hyperopia. PMID- 2248916 TI - Lamellar keratoplasty combined with extracapsular cataract extraction. PMID- 2248918 TI - Correction of astigmatism after cataract surgery. PMID- 2248919 TI - Disclosure of potential conflict of interest. PMID- 2248920 TI - Contrast sensitivity under photopic conditions in the Prospective Evaluation of Radial Keratotomy (PERK) Study. AB - We studied the effect of radial keratotomy on contrast sensitivity in 69 individuals with one eye operated and one eye unoperated in the Prospective Evaluation of Radial Keratotomy (PERK) Study, with a mean follow-up time of 13.8 months (range 6 months to 31 months). We tested contrast sensitivity under normal daylight conditions using both photographic plates and a computer-video apparatus. On average, we found no clinically meaningful loss of contrast sensitivity in eyes after radial keratotomy. However, eyes with radial keratotomy showed a statistically significant decrease in contrast sensitivity at the higher spatial frequencies of 12 and 18 cycles per degree, although all values were within the previously established normal range. Specifically, 44% of the patients had approximately the same contrast sensitivity in both eyes; 40% of the patients had 50% less contrast sensitivity in the operated eye than in the unoperated eye; 16% of the patients had 50% more contrast sensitivity in the operated eye than in the unoperated eye. Contrast sensitivity improved gradually in operated eyes between 6 months and 2 years after surgery. Eyes with radial keratotomy, in which the diameter of the pupil was the same size as or larger than the central clear zone, had slightly decreased contrast sensitivity compared to eyes in which the pupil was smaller than the clear zone. PMID- 2248921 TI - Epidermal growth factor and insulin in use in corneal preservation: study design and objectives of a multi-center trial. AB - This study determines whether endothelial survival after penetrating keratoplasty is improved by adding the mitogens, human epidermal growth factor (hEGF), and human insulin to a chondroitin-sulfate-based corneal storage medium. It is a multicenter, prospective, double-masked, randomized trial that compares endothelial survival of human corneal transplants using donor corneas that have been stored in one of two media: DexSol (CSM with 1% dextran) or DexSol containing recombinant hEGF and human insulin. This article describes the study design and entry characteristics of the 105 recipient pairs. Each donor pair of corneas is transplanted on the same day into recipients who are matched by diagnosis and procedure. Clinical parameters assessed on day 1, week 1, and 3, 6 and 12 months postoperatively include graft clarity, epithelial integrity, corneal thickness, visual acuity, and intraocular pressure. Postoperative endothelial survival for both groups will be determined by morphometric analysis of endothelial cell images before storage and at 3, 6, and 12 months postoperatively. Such analysis will also identify differences in polymegathism (cell size) or pleomorphism (cell shape). PMID- 2248922 TI - Ablation rate of human corneal epithelium and Bowman's layer with the excimer laser (193 nm). AB - Laser keratomileusis is a laser-specific procedure whereby a layer of corneal tissue as thin as 10 microns or more is removed from the anterior surface. In most cases, the laser ablates not only Bowman's layer but also portions of the anterior stroma. The histologic evaluation presented shows that the ablation behavior of these two layers is not uniform: at a fluence of 205 mJ/cm2 in Bowman's layer, the ablation rate was 0.38 +/- 0.05 microns per pulse, whereas in stroma it amounted to 0.55 +/- 0.1 microns per pulse. In epithelium, the ablation rate was 0.68 +/- 0.15 microns per pulse, but decreased with deeper excisions. We discuss the consequences of these different ablation rates on the procedure of laser keratomileusis. PMID- 2248923 TI - Excimer laser (193 nm) myopic keratomileusis in sighted and blind human eyes. AB - Ten blind and 13 sighted human eyes underwent excimer laser (193 nm) keratomileusis. The radiant exposure was 180 mJ/cm2 with an ablation zone diameter of 3.5 mm. The follow-up of the blind eyes ranged from 9 to 11 months, whereas that of the sighted eyes was at least 6 months. The intended refraction change was -3.0 and -5.0 D in the blind eyes and ranged from -1.5 to -7.0 D in the sighted eyes. After 3 months, 12 of 13 sighted eyes (92%) achieved a refraction between +/- 1.0 D, whereas after 6 months 77% of the refractions were in this range. Temporary subepithelial haze occurred in all eyes except some of the -3.0 D blind eyes. After 6 months, the subepithelial haze had resolved to a clinical non-significant level (trace to grade 0.5 haze), except in one eye that showed a focal scar. PMID- 2248924 TI - Refractive versus keratometric astigmatism postkeratoplasty. AB - In patients who had undergone penetrating keratoplasty, we compared the relationship between keratometric astigmatism and actual refractive cylinder required for visual correction in 115 eyes postoperatively. The average time from surgery to refraction was 49.5 months and from surgery to keratometry 50.3 months. Sixty-five eyes retaining their running 10-0 nylon sutures had an average of 5.43 diopters of keratometric cylinder and 2.95 D of refractive cylinder. The difference was highly statistically significant (P less than .001). This significant difference was true in eyes with keratoconus and Fuchs' endothelial dystrophy. In 50 eyes with all sutures removed, the average keratometry reading revealed 4.27 D of astigmatism while the cylindrical refraction required in spectacles averaged 3.70 D. The difference was not statistically significant (P = .018). The significant difference between astigmatism as measured by keratometry and by refraction in eyes with the sutures still in place should be taken into consideration when using suture removal or adjusting techniques after keratoplasty. PMID- 2248925 TI - Simultaneous and sequential selective suture removal to reduce astigmatism after penetrating keratoplasty. AB - We studied two separate groups of consecutive eyes with penetrating keratoplasty in avascular corneas in which we performed selective interrupted suture removal to decrease postoperative astigmatism, describing the time course of change in astigmatism. In the first group (29 eyes), multiple interrupted sutures were selectively removed at a single visit in an attempt to reduce the astigmatism to less than or equal to 3 diopters; the patients were followed for 30 months. In the second group (24 eyes), one interrupted suture was removed at each visit every 2 weeks until the astigmatism was less than or equal to 3 D; the patients were followed for 15 months. Surgical techniques were different in the two groups. Both techniques reduced postoperative astigmatism. Larger changes in astigmatism occurred between the first suture removal visit and the subsequent visit in the first group. At 1 year, the multiple-suture-removal-at-a-single visit group averaged 3.1 D of astigmatism, with 50% of eyes less than or equal to 3 D, whereas the single-suture-removal-at-multiple-visits group had a mean astigmatism of 1.9 D with 88% of eyes less than or equal to 3 D. The two groups we studied were not directly comparable, because surgical techniques differed, because they were operated at different times, and because the cases were not randomized. Nevertheless, we think that selective suture removal to reduce astigmatism after penetrating keratoplasty is best done by removing only one (or sometimes two) sutures per examination. PMID- 2248926 TI - Clinicopathologic study of healing excimer laser radial excisions. AB - Four radial linear excisions were created by an argon fluoride (193 nm) excimer laser in the edematous cornea of a blind eye of a diabetic human patient. Partial thickness corneal trephinations were performed at 3, 7, and 18 months after surgery for histopathologic examination. At 3 months, a wide gap in Bowman's layer permitted extension of an epithelial plug to a depth of 0.35 mm; at 7 and 18 months, the depth of the epithelial plug was decreased to 0.29 mm and 0.01 mm, respectively. With wound healing, excision width decreased and the two cut ends of Bowman's layer were almost reapposed by 18 months, suggesting wound contraction. Linear excisions with the excimer laser appear to be wider than incisions made with a diamond blade, but the pattern of wound maturation appears to be similar. PMID- 2248927 TI - Scanning electron microscopic evaluation of the effects of intracameral injection of cyanoacrylate in the rabbit. AB - We examined, using scanning electron microscopy, the effects of the injection of an isobutyl cyanoacrylate into the rabbit anterior chamber. Injection of the adhesive produced a rapidly polymerized mass that remained in the anterior chamber throughout the course of the study. Additionally, an active inflammatory response was noted in the anterior chamber, characterized by a progressively enlarging "cocoon" of fibrin and inflammatory cells surrounding the polymerized adhesive, as well as inflammatory cells in the trabecular meshwork. Following cyanoacrylate injection, the corneal endothelial cells were noted to be swollen for the first 14 days of the study. PMID- 2248928 TI - Corneal rupture from blunt trauma 22 months after radial keratotomy. AB - This report describes a case of traumatic corneal rupture 22 months after radial keratotomy in a 39-year-old woman. The patient struck her face on the side of her car resulting in a limbus rupture in her cornea through the horizontal incisions of a four-incision radial keratotomy. An orbital blowout fracture was also present. A sclerotomy was performed to drain persistent choroidal detachment. After the hemorrhage in the anterior chamber resolved, the iris and lens were found to be absent. Visual acuity of 20/40 was achieved with aphakic correction. PMID- 2248929 TI - The importance of corneal asphericity and irregular astigmatism in refractive surgery. PMID- 2248930 TI - Globe holder and artificial anterior chamber. PMID- 2248931 TI - SCMD keratome unit. PMID- 2248932 TI - Escalation of keratospeak: regular and irregular astigmatism. PMID- 2248933 TI - Radial keratotomy: what are the limits? PMID- 2248934 TI - Computed tomography in the diagnosis of maxillofacial trauma. AB - A study of 34 patients who were investigated for maxillofacial trauma using high resolution computed tomography (CT) scanning is presented. The areas where this increasingly available technique offers more accurate information than conventional plain radiographs are discussed. PMID- 2248935 TI - Cross-match requirements in orthognathic surgery: an audit. AB - A retrospective audit was undertaken of the value of routine cross-matching of blood for patients undergoing orthognathic surgery at Canniesburn Hospital, Glasgow. Overall, routine cross-matching of blood was wasteful of resources for all but the more major types of osteotomy procedure: Le Fort III, Le Fort II, malar osteotomies requiring a bicoronal flap and bimaxillary osteotomies. The study has financial implications regarding the proper use of cross-matching in selected patients undergoing elective orthognathic surgery. A blood ordering tariff has been suggested for the various procedures studied. PMID- 2248936 TI - Traumatic aneurysms of the internal maxillary artery and their treatment by embolisation: a report of two cases. AB - Traumatic aneurysms of the head and neck are rare lesions and in the past their treatment has been by a variety of surgical approaches. Two civilian cases of traumatic aneurysm of the internal maxillary artery are reported. These were treated by embolisation, which offered for their management an effective alternative and less invasive approach than surgery. PMID- 2248937 TI - Adie's pupil following Le Fort I maxillary osteotomy. A complication or coincidence? AB - A case is reported of right-sided tonic pupil in isolation (Adie's pupil) following Le Fort I maxillary osteotomy. It is difficult to identify whether this rare finding immediately postoperatively is either a pure coincidence or a genuine complication of surgery. PMID- 2248938 TI - Lingual cellulitis causing upper airway obstruction. AB - A case is reported in which upper airway obstruction occurred in an immunosuppressed patient due to the presence of lingual cellulitis. PMID- 2248939 TI - Benign osteoblastoma of the mandible. AB - Benign osteoblastoma is a rare osteoblastic tumour with osteoid and bone deposition. A rapidly growing osteoblastoma involving the area of the mandibular first and second molar of a 20-year-old female is described. Investigation of the collagenous components of the tumour by immunofluorescence was suggestive of a normal collagen synthesis by the tumour osteoblasts. The lesion is discussed with particular emphasis on its differential diagnosis and matrix constituents. PMID- 2248940 TI - The mandibular infected buccal cyst (paradental cyst). A radiographic and histological study. AB - Mandibular infected buccal cysts occur on the buccal and distal aspects of the roots of partly or fully erupted mandibular molars with vital pulps. In the present investigation six cases associated with mandibular first and second molars were studied. The cysts were lined with a non-keratinised squamous epithelium with a mixed inflammatory cell infiltrate in the connective tissue. The clinical and microscopic features were similar to those of previously reported paradental cysts. The inflammation always present in these cysts may have an important role in their pathogenesis. It may induce periodontal pocketing, which may lead to hyperplasia and cyst formation in adjacent odontogenic epithelium, which may be either remnants of the reduced enamel epithelium or cell rests of Malassez. PMID- 2248941 TI - Necrotizing sialometaplasia: report of 12 new cases. AB - The clinical and histopathological findings of 12 new cases of necrotizing sialometaplasia are described. PMID- 2248942 TI - Lymphoepithelial cyst of the parotid gland. AB - A case of a lymphoepithelial cyst presenting as a parotid tumour is described. Aspects of diagnosis and management are discussed, as well as current theories on the origin and development of lymphoepithelial (branchial) cysts. PMID- 2248943 TI - Hereditary gingival fibromatosis associated with growth hormone deficiency. AB - A case report of gingival fibromatosis in association with growth hormone (GH) deficiency due to a lack of growth hormone releasing factor (GRF) is presented. The girl is the youngest member of a family of eight children, five of whom lack the same hormone and have or have had similar gingival enlargements. After the growth hormone deficiency had been diagnosed and hormone substitute administered the dental age of the girl presented came closer to that of her age and sex matched controls but did not reach the corresponding values even though the teeth were exposed by excising the overgrown gingiva. Test fibroblasts cultured from the overgrown gingiva proliferated at a slower rate than those cultured from age matched controls. Total RNA was extracted from the test and three control fibroblasts and examined by Northern hybridisation using cDNAs for pro alpha 1(I) and pro alpha 1(III) chains. The amount of type I and III procollagen mRNAs were lower in the test fibroblasts as compared to the controls. PMID- 2248944 TI - Primary bone cyst of the mandibular condyle. AB - Cysts of the mandibular condyle are rare and their diagnosis and treatment can be difficult. A case in a young girl is described where the histology was that of a solitary bone cyst but the presentation and behaviour more closely resembled an aneurysmal bone cyst. PMID- 2248945 TI - Odontoameloblastoma: a case report. AB - Confusion in the early literature regarding the odontoameloblastoma, resulted in this tumour being reported under a variety of names. Many of the reported cases fail to meet the clinical and histological criteria required for classification as odontoameloblastomata. This article attempts to present a case with clinical, radiological and histological features that meet the required criteria. In this case the ameloblastic component intermingled with the dental hard tissues. PMID- 2248946 TI - Computer hardware and surgical audit. PMID- 2248947 TI - Fatty acid binding sites of rodent adipocyte and heart fatty acid binding proteins: characterization using fluorescent fatty acids. AB - Murine adipocyte and rat heart fatty acid binding proteins (FABP) are closely related members of a family of cytosolic proteins which bind long-chain free fatty acids (ffa). The physical and chemical characteristics of the fatty acid binding sites of these proteins were studied using a series of fluorescent analogues of stearic acid (18:0) with an anthracene moiety covalently attached at seven different positions along the length of the hydrocarbon chain (AOffa). Previously, we used these probes to investigate the binding site of rat liver FABP (L-FABP) [Storch et al. (1989) J. Biol. Chem. 264, 8708-8713]. Here we extend those studies to adipocyte and heart FABP, two members of the FABP family which share a high degree of sequence homology with each other (62% identity) but which are less homologous with L-FABP (approximately 30%). The results show that the fluorescence emission spectra of AOffa bound to adipocyte FABP (A-FABP) are blue-shifted relative to heart FABP (H-FABP), indicating that AOffa bound to A FABP are held in a more constrained configuration. For both proteins, constraint on the bound ffa probe is highest at the midportion of the acyl chain. Ffa are bound in a hydrophobic environment in both proteins. Excited-state lifetimes and fluorescence quantum yields suggest that the binding site of H-FABP is more hydrophobic than that of A-FABP. Nevertheless, acrylamide quenching experiments indicate that ffa bound to H-FABP are more accessible to the aqueous environment than are A-FABP-bound ffa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248948 TI - Small-angle scattering studies show distinct conformations of calmodulin in its complexes with two peptides based on the regulatory domain of the catalytic subunit of phosphorylase kinase. AB - Small-angle X-ray and neutron scattering have been used to study the solution structures of calmodulin complexed with synthetic peptides corresponding to residues 342-366 and 301-326, designated PhK5 and PhK13, respectively, in the regulatory domain of the catalytic subunit of skeletal muscle phosphorylase kinase. The scattering data show that binding of PhK5 to calmodulin induces a dramatic contraction of calmodulin, similar to that previously observed when calmodulin is complexed with the calmodulin-binding domain peptide from rabbit skeletal muscle myosin light chain kinase. In contrast, calmodulin remains extended upon binding PhK13. In the presence of both peptides, calmodulin also remains extended. Apparently, the presence of PhK13 inhibits calmodulin from undergoing the PhK5-induced contraction. These data indicate that there is a fundamentally different type of calmodulin-target enzyme interaction in the case of the catalytic subunit of phosphorylase kinase compared with that for myosin light chain kinase. PMID- 2248949 TI - High-resolution three-dimensional structure of a single zinc finger from a human enhancer binding protein in solution. AB - The three-dimensional structure of a 30-residue synthetic peptide containing the carboxy-terminal "zinc finger" motif of a human enhancer binding protein has been determined by two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on 487 approximate interproton distance and 63 torsion angle (phi, psi, and chi 1) restraints. A total of 40 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 29 and 30 which are ill-defined) is 0.4 A for the backbone atoms, 0.8 A for all atoms, and 0.41 A for all atoms excluding the lysine and arginine side chains, which are disordered. The solution structure of the zinc finger consists of two irregular antiparallel beta-strands connected by an atypical turn (residues 3-12) and a classical alpha-helix (residues 14-24). The zinc is tetrahedrally coordinated to the sulfur atoms of two cysteines (Cys-5 and Cys-8) and to the N epsilon 2 atoms of two histidines (His-21 and His-27). The two cysteine residues are located in the turn connecting the two beta-strands (residues 5-8); one of the histidine ligands (His-21) is in the alpha-helix, while the second histidine (His-27) is at the end of a looplike structure (formed by the end of the alpha-helix and a turn). The general architecture is qualitatively similar to two previously determined low-resolution Cys2-His2 zinc finger structures, although distinct differences can be observed in the beta strands and turn and in the region around the two histidines coordinated to zinc. Comparison of the overall polypeptide fold of the enhancer binding protein zinc finger with known structures in the crystallographic data base reveals a striking similarity to one region (residues 23-44) of the X-ray structure of proteinase inhibitor domain III of Japanese quail ovomucoid [Papamokos, E., Weber, E., Bode, W., Huber, R., Empie, M. W., Kato, I., & Laskowski, M. (1982) J. Mol. Biol. 158, 515-537], which could be superimposed with a backbone atomic rms difference of 0.95 A on residues 3-25 (excluding residue 6) of the zinc finger from the enhancer binding protein. The presence of structural homology between two proteins of very different function may indicate that the so-called zinc finger motif is not unique for a class of DNA binding proteins but may represent a general folding motif found in a variety of proteins irrespective of their function. PMID- 2248950 TI - Fluorescence investigation of the sex steroid binding protein of rabbit serum: steroid binding and subunit dissociation. AB - The relationship between steroid binding and protein subunit interactions of rabbit sex steroid binding protein (rSBP) has been studied by steady-state and time-resolved fluorescence spectroscopy. The high-affinity (Ka approximately 10(8) M-1 at 4 degrees C), fluorescent estrogen d-1,3,5(10),6,8-estrapentaene 3,17 beta-diol [dihydroequilenin (DHE)] was used as a fluorescent probe of the steroid-binding site. Perturbation of the binding site with guanidinium chloride (Gdm.Cl) was monitored by changes in the steady-state fluorescence anisotropy of DHE as well as by changes in fluorescence quenching of DHE with acrylamide. The results of acrylamide quenching at 11 degrees C show that, while between 0 and 1 M Gdm.Cl the steroid-binding site is completely shielded from bulk solvent, there is decreased DHE binding. To study the subunit-subunit interactions, rSBP was covalently labeled with dansyl chloride in the presence of saturating 5 alpha dihydrotestosterone (DHT), which yielded a dansyl-conjugated protein that retained full steroid-binding activity. The protein subunit perturbation was monitored by changes in the steady-state fluorescence anisotropy of the dansyl group. At 11 degrees C, the dansyl anisotropy perturbation, reflecting changes in global and segmental motions of the dimer protein, occurs at concentrations of Gdm.Cl above 1 M. The Gdm.Cl titration in the presence of steroids with equilibrium association constants less than 10(8) M-1 shows a plateau near 3 M Gdm.Cl at 11 degrees C; at this Gdm.Cl concentration, no DHE is bound. No plateau is observed at 21 degrees C. At higher Gdm.Cl concentrations, the dansyl fluorescence anisotropy decreases further and shows no steroid dependence. Recovery of steroid-binding activity (assayed by saturation binding with [3H]DHT), under renaturation conditions, is dependent on both steroid concentration and affinity. Both unlabeled and dansyl-labeled protein recovery the same amount of activity, and according to fluorescence anisotropy, dansyl labeled rSBP re-forms a dimer upon dilution below 1 M or removal of Gdm.Cl. From the steroid requirement for recovery of steroid-binding activity, it appears that a conformational template is required for the dimeric protein to re-form a steroid-binding site with native-like properties. PMID- 2248951 TI - Estimating the contribution of engineered surface electrostatic interactions to protein stability by using double-mutant cycles. AB - Coulombic interactions between charges on the surface of proteins contribute to stability. It is difficult, however, to estimate their importance by protein engineering methods because mutation of one residue in an ion pair alters the energetics of many interactions in addition to the coulombic energy between the two components. We have estimated the interaction energy between two charged residues, Asp-12 and Arg-16, in an alpha-helix on the surface of a barnase mutant by invoking a double-mutant cycle involving wild-type enzyme (Asp-12, Thr-16), the single mutants Thr----Arg-16 and Asp----Ala-12, and the double mutant Asp--- Ala-12, Thr----Arg-16. The changes in free energy of unfolding of the single mutants are not additive because of the coulombic interaction energy. Additivity is restored at high concentrations of salt that shield electrostatic interactions. The geometry of the ion pair in the mutant was assumed to be the same as that in the highly homologous ribonuclease from Bacillus intermedius, binase, which has Asp-12 and Arg-16 in the native enzyme. The ion pair does not form a hydrogen-bonded salt bridge, but the charges are separated by 5-6 A. The mutant barnase containing the ion pair Asp-12/Arg-16 is more stable than wild type by 0.5 kcal/mol, but only a part of the increased stability is attributable to the electrostatic interaction. We present a formal analysis of how double mutant cycles can be used to measure the energetics of pairwise interactions. PMID- 2248952 TI - Glycine to alanine substitutions in helices of glyceraldehyde-3-phosphate dehydrogenase: effects on stability. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from chicken was expressed in and purified from Escherichia coli. To investigate the physical basis of possible protein stabilization strategies, the effect of substitutions of glycine residues by alanine in helical regions was determined. One Gly to Ala substitution (G316A) located in the central core of the subunit was found to strongly stabilize the protein, while the other mutations are neutral or destabilize the protein. The effect seen for the stabilizing mutant in irreversible heat denaturation correlates with the first transition in folding equilibrium experiments that is observable by fluorescence, but not with the one detected by circular dichroism measurements or in dilution-induced dissociation experiments. The stabilizing effect of a Gly to Ala substitution therefore does not seem to be caused by an entropic effect on the unfolded state. Rather, an internal cavity is filled by the substitution G316A, probably stabilizing the native state. In large oligomeric proteins, imperfect packing may be a frequent cause of limited stability. PMID- 2248953 TI - Point charge distributions and electrostatic steering in enzyme/substrate encounter: Brownian dynamics of modified copper/zinc superoxide dismutases. AB - The electrostatic steering mechanism of bovine erythrocyte Cu/Zn superoxide dismutase (SOD) was investigated through the use of Brownian dynamics. Simulations of enzyme/substrate encounter were carried out on 14 different SOD models defined by simple changes in the enzyme's point charge distribution. The magnitude and ionic strength dependence of reaction rates, rates for collision anywhere on the enzyme surface, and collision efficiency factors were analyzed to elucidate both the general and specific roles for point charges associated with amino acid residues. Collision rates for the general enzyme surface appear to be solely determined by the net charge on the enzyme. At physiological ionic strength this effect is negligible, with only 6% variation in collision rates observed as the net charge ranges from +2e to -10e. With the exception of a few charged residues in the active-site channel of SOD, point charge modifications had modest effects on reaction rates. For a large region within and surrounding the channel, reaction rates increased or decreased by only 10-15% with the addition or subtraction of a protonic unit of charge, respectively. This effect simply disappeared with increasing distance from the active site. More dramatic effects were seen at only three residues: arginine-141, glutamate-131, and lysine 134. Implications for rate enhancement through site-directed mutagenesis are discussed. PMID- 2248954 TI - Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin. AB - Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripeptide substrate and for antithrombin III inhibition rate constants, from those of the unmodified enzyme. The 10,000-fold rate enhancement elicited by the addition of heparin to the antithrombin III inhibition reaction, however, is the same. The observed second order rate constants (k"obs) for antithrombin III inhibition of factor Xa and methylated factor Xa are 3000 and 340 M-1 s-1, respectively, whereas k"obs values for the inhibition of factor Xa or methylated factor Xa with antithrombin III heparin are 4 X 10(7) and 3 X 10(6) M-1 s-1, respectively. These findings provide direct evidence that the interaction of factor Xa with heparin is not involved in the heparin-enhanced inhibition of this enzyme. PMID- 2248955 TI - Proteolytic activation of human factors IX and X by recombinant human factor VIIa: effects of calcium, phospholipids, and tissue factor. AB - Previous studies indicated that factor VIIa, in complex with tissue factor, readily activates either factor X or factor IX in the presence of calcium ions. In order to assess the relative physiological importance of the activation of factor IX versus the activation of factor X by recombinant factor VIIa, we have obtained steady-state kinetic parameters for the factor VIIa catalyzed activation of factor IX and factor X under a variety of cofactor conditions that include calcium alone, calcium and phospholipids, calcium, phospholipids, and tissue factor apoprotein, and calcium and cell-surface tissue factor. Calcium alone stimulated the activation of factors IX and X by factor VIIa maximally at 1 and 2.5 mM, respectively. In the presence of 25 microM phospholipids, maximal rates of factor IX and factor X activation were achieved at 2.5-5 mM calcium. With calcium alone, or with phospholipid and calcium, the initial rates of factor IX activation by factor VIIa were significantly higher than that observed for factor X. Kinetic studies revealed that the Km for the factor VIIa catalyzed activation of factor IX was essentially constant in the presence of 5 mM calcium and 1-500 microM phospholipid, whereas the Km for factor X activation varied with phospholipid concentration, reaching a minimum at 7-20 microM phospholipid. At all concentrations of added phospholipid, the kcat/Km ratio for the activation of factor IX by factor VIIa appeared to be considerably greater than that observed for the activation of factor X.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248956 TI - Length-dependent formation of parallel-stranded DNA in alternating AT segments. AB - Parallel-stranded DNA can be formed from alternating AT segments and is not restricted exclusively to homooligomeric AT sequences. DNA oligonucleotides 3' d(AT)nxC4(AT)n-3' (where x indicates the location of the 5'-5' phosphodiester linkage) form parallel-stranded hairpin structures at micromolar strand concentration for n = 4 or 5 but not for n = 6, 7. The spectral properties of the parallel-stranded structures are similar to those of the hairpin structures containing homooligomeric AT stems. However, parallel-stranded structures formed in alternating AT segments are significantly less stable than either their corresponding antiparallel control or the homooligomeric parallel AT hairpins as evidenced by their lower helix-coil transition enthalpy, melting temperature, and stability constant. This results in a remarkable polymorphism which is most pronounced for 3'-d(AT)5xC4(AT)5-3'. This oligonucleotide can exist as a parallel stranded hairpin, coil, or concatameric antiparallel structure(s), depending on temperature and strand concentration. These results suggest simple guidelines for the design of parallel-stranded DNA. In addition, we present a model for the assessment of the stability of parallel-stranded duplex structures formed from AT base pairs based on their sequence. PMID- 2248957 TI - Organization, structure, and polymorphisms of the human profilaggrin gene. AB - Profilaggrin is a major protein component of the keratohyalin granules of mammalian epidermis. It is initially expressed as a large polyprotein precursor and is subsequently proteolytically processed into individual functional filaggrin molecules. We have isolated genomic DNA and cDNA clones encoding the 5' and 3'-ends of the human gene and mRNA. The data reveal the presence of likely "CAT" and "TATA" sequences, an intron in the 5'-untranslated region, and several potential regulatory sequences. While all repeats are of the same length (972 bp, 324 amino acids), sequences display considerable variation (10-15%) between repeats on the same clone and between different clones. Most variations are attributable to single-base changes, but many also involve changes in charge. Thus, human filaggrin consists of a heterogeneous population of molecules of different sizes, charges, and sequences. However, amino acid sequences encoding the amino and carboxyl termini are more conserved, as are the 5' and 3' DNA sequences flanking the coding portions of the gene. The presence of unique restriction enzyme sites in these conserved flanking sequences has enabled calculations on the size of the full-length gene and the numbers of repeats in it: depending on the source of genomic DNA, the gene contains 10, 11, or 12 filaggrin repeats that segregate in kindred families by normal Mendelian genetic mechanisms. This means that the human profilaggrin gene system is also polymorphic with respect to size due to simple allelic differences between different individuals. The amino- and carboxyl-terminal sequences of profilaggrin contain partial or truncated repeats with unusual un-filaggrin-like sequences on the termini.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248958 TI - Purification of human smooth muscle filamin and characterization of structural domains and functional sites. AB - A method was developed to purify human smooth muscle filamin in high yield and structural domains were defined by using mild proteolysis to dissect the molecule into intermediate-sized peptides. Unique domains were defined and aligned by using high-resolution peptide mapping of iodinated peptides on cellulose plates. The amino- and carboxyl-terminal orientation of these domains within the molecule was determined by amino acid sequence analysis of several aligned peptides. In addition to the three unique domains which were identified, a number of smaller and larger fragments were also characterized and aligned within the intact molecule. These structural domains and related peptides provide a useful set of defined fragments for further elucidation of structure-function relationships. The two known functionally important binding sites of filamin, the self association site and the actin-binding site, have been localized. Self association of two monomers in a tail-to-tail orientation involves a small protease-sensitive region near the carboxyl terminal of the intact polypeptide chain. Sedimentation assays indicate that an actin-binding site is located near the blocked amino terminal of the filamin molecule. Sequences derived from large peptides mapping near the amino terminal show homology to the amino-terminal actin-binding site of alpha-actinin (chicken fibroblast and Dictyostelium), Dictyostelium 120-kDa actin gelation factor, beta-spectrin (human red cell and Drosophila), and human dystrophin. This homology is particularly interesting for two reasons. The functional form of filamin is single stranded, in contrast to alpha-actinin and spectrin which are antiparallel double-stranded actin cross linkers. Also, no homology to the spectrin-like segments which comprise most of the mass of spectrin, alpha-actinin, and dystrophin was found. Instead, the sequence of a domain located near the center of the filamin molecule (tryptic 100 kDa peptide, T100) shows homology to the published internal repeats of the Dictyostelium 120-kDa actin gelation factor. On the basis of these results, a model of human smooth muscle filamin substructure is presented. Also, comparisons of human smooth muscle filamin, avian smooth muscle filamin, and human platelet filamin are reported. PMID- 2248959 TI - Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. AB - The 2.3-A crystal structure of recombinant human dihydrofolate reductase (EC 1.5.1.3, DHFR) has been solved as a binary complex with folate (a poor substrate at neutral pH) and also as a binary complex with an inhibitor, 5-deazafolate. The inhibitor appears to be protonated at N8 on binding, whereas folate is not. Rotation of the peptide plane joining I7 and V8 from its position in the folate complex permits hydrogen bonding of 5-deazafolate's protonated N8 to the backbone carbonyl of I7, thus contributing to the enzyme's greater affinity for 5 deazafolate than for folate. In this respect it is likely that bound 5 deazafolate furnishes a model for 7,8-dihydrofolate binding and, in addition, resembles the transition state for folate reduction. A hypothetical transition state model for folate reduction, generated by superposition of the DHFR binary complexes human.5-deazafolate and chicken liver.NADPH, reveals a 1-A overlap of the binding sites for folate's pteridine ring and the dihydronicotinamide ring of NADPH. It is proposed that this binding-site overlap accelerates the reduction of both folate and 7,8-dihydrofolate by simultaneously binding substrate and cofactor with a sub van der Waals separation that is optimal for hydride transfer. PMID- 2248960 TI - Phospholipid vesicle solubilization and reconstitution by detergents. Symmetrical analysis of the two processes using octaethylene glycol mono-n-dodecyl ether. AB - The processes of liposome solubilization and reconstitution were studied by using n-dodecyl octaethylene glycol monoether (C12E8). The solubilization of large unilamellar liposomes prepared by reverse-phase evaporation was systematically investigated by turbidity, 31P nuclear magnetic resonance, and centrifugation experiments. The solubilization process is well described by the three-stage model previously proposed for other detergents, and our results further demonstrate the validity of some of the postulates related to this model. In stage I, the detergent distributes between the bilayers and the aqueous solution with a partition coefficient of 1.6 mM-1. In stage II, the detergent-saturated liposomes convert into mixed micelles, the conversion being complete by stage III where all the phospholipids are present as mixed micelles. The agreement between the three methods was excellent, and the results allowed quantitative determination of the effective detergent to phospholipid ratios at which the lamellar to micellar transformation begins and is complete, which amounted to 0.66 and 2.2 (mol/mol), respectively. Furthermore, compositional analysis determined from centrifugation experiments directly demonstrate that the properties of detergent-saturated liposomes and mixed micelles remain constant throughout most of stage II: the C12E8 to phospholipid ratios in the pelleted vesicles and in micelles are constant during stage II and similar to the ratios at which stage II was initiated and complete, respectively. On the other hand, bilayer formation upon detergent removal from mixed C12E8-phospholipid micelles by SM2 Bio-Beads is demonstrated to be the symmetrical opposite of bilayer solubilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2248961 TI - Epidermal growth factor stimulated phosphorylation of a 120-kilodalton endogenous substrate protein in rat hepatocytes. AB - Endogenous substrates of the EGF receptor have been described in transformed cells; however, little is known about substrates in normal tissue. To characterize epidermal growth factor (EGF) receptor phosphorylation and search for endogenous substrates in normal rat hepatocytes, cells were labeled with [32P]orthophosphate, and phosphotyrosine-containing proteins were sought by using a high-affinity, specific anti-phosphotyrosine antibody. Exposure of 32P-labeled freshly isolated hepatocytes to 1 microgram/mL EGF caused phosphorylation of several proteins of Mr 185K, 160K, and 120K. The 185- and 160-kDa proteins (pp185 and pp160) were identified as the intact and proteolyzed forms of the EGF receptor by virtue of their immunoprecipitation with anti-EGF receptor antibody. This antibody failed to recognize the 120-kDa phosphoprotein (pp120). The phosphopeptide map derived from pp120 was by trypsinization and HPLC separation different from that of pp185, further indicating that pp120 is distinct from the EGF receptor. This pp120 was also immunologically distinct from the pp120 substrate of the insulin receptor kinase and from ATP-citrate lyase. Phosphoamino acid analysis revealed pp120 to be phosphorylated on both tyrosine and serine residues. Autophosphorylation of EGF receptor and phosphorylation of pp120 were almost maximal within 1 min of EGF stimulation. The dose-response curves for phosphorylation of the EGF receptor and pp120 were identical (ED50 = 30 ng/mL) and were superimposable with the fractional occupancy of the EGF receptor. In A431 cells, a transformed cell line whose growth is inhibited by EGF, EGF produced a decrease in pp120 phosphorylation. These data suggest that pp120 is an endogenous substrate for the EGF receptor in hepatocytes whose phosphorylation may be closely related to EGF stimulation of cell growth. PMID- 2248962 TI - Combination of 31P-NMR magnetization transfer and radioisotope exchange methods for assessment of an enzyme reaction mechanism: rate-determining steps of the creatine kinase reaction. AB - The theoretical analysis of a reversible enzyme reaction performed in this work shows that the 31P-NMR magnetization (saturation) transfer technique combined with a radioisotope exchange method may potentially provide information on the position of rate-determining step(s). It depends on chemical shifts of NMR signals of nuclei of interest in free and enzyme-bound forms of substrate(s) and product(s) of the reaction. The creatine kinase reaction (MgATP + creatine--- MgADP + P-creatine) has been used as a model. Chemical shifts of 31P in binary, ternary and transitional state substrate-enzyme complexes have been estimated by the variable frequency saturation transfer (VFST) method. This method is based on selective irradiation of numerous points in the spectrum and observation of changes in the intensity of visible line(s) which occur due to chemical exchange between it and lines which are not visible in the routine spectrum. Also, dissociation rate constants of MgADP-containing complexes were determined. Magnetization exchange rates, P-creatine----[gamma-P]MgATP and [beta-P]MgADP--- [beta-P]MgATP, were compared with radioisotope exchange rates, [gamma-32P-MgATP-- -P-creatine and [3H]MgADP----MgATP at different [P-creatine]/[creatine] ratios and at different temperatures. All these exchange rates were close to each other at 30-37 degrees C and [PCr]/[Cr] ratios lower than 2. It is concluded that phosphoryl group transfer is the rate-determining step of the overall creatine kinase reaction under these conditions. However, at lower temperatures (below 25 degrees C) or at high [PCr]/[Cr] ratios ([ADP] less than 20 microM) the rate determining step seems to be shifted toward dissociation of nucleotide substrates from enzyme-substrate complexes, since exchange rates became significantly different. This approach is useful for analysis of mechanism of enzymatic reactions and also can be applied to non-enzymatic reactions and evaluation of small rapidly exchangeable metabolite pools. PMID- 2248963 TI - Deuterium NMR study of the interaction of phytanic acid and phytol with the head group region of a phospholipid bilayer. Evidence of magnetic orientation. AB - Deuterium nuclear magnetic resonance (2H-NMR) spectra of multilamellar dispersions of 1,2-dipalmitoyl-sn-glycero-3-phospho-[1',2'-methylene-2H4]choline (DPPC-d4) containing 20 mol% of the isoprenoid compounds phytol or phytanic acid in excess deuterium-depleted water, or Tris buffer (pH 7.4), have been recorded over the temperature range 15-55 degrees C. Phytol (20 mol%) causes a decrease in the residual quadrupolar splitting, delta vQ, of the choline 1'-deuterons (i.e., those adjacent to the phosphate moiety) by 3%, while delta vQ, of the 2' deuterons decrease by 22%. Phytanic acid (20 mol%) reduces delta vQ of the 2' deuterons by 43% and increases delta vQ of the 1'-deuterons by approx. 16%. First (M1) and second (M2) moments were calculated from the spectra. Plots of M1 and M2 versus temperature suggest phytol and phytanic acid have a significant effect on the pretransition. Spin-lattice relaxation times (T1) and transverse relaxation times (T2e, the time constant for decay of the quadrupolar echo) have been determined over the temperature range 15-50 degrees C. The presence of 20 mol% phytanic acid results in orientation of the DPPC bilayers in the magnetic field with the phospholipid long axes oriented perpendicular to the magnetic field as shown by 2H- and 31P-NMR. The sample must be carried through several freeze-thaw cycles in the presence of Tris buffer in order that the phospholipid magnetic field ordering occur. Possible explanations for the effect of phytol and phytanic acid on the dynamic structure of the choline head group of phospholipids in the bilayer are suggested. PMID- 2248964 TI - Effect of experimental conditions on the appearance of distinct forms of placental glucosylceramidase: use of gel filtration analysis as a means of ascertaining their occurrence. AB - We have found that, under some experimental conditions, the placental glucosylceramidase shows an anomalous behaviour on gel filtration chromatography. At pH 5.6, the optimal pH of the enzymatic assay, the purified enzyme remains bound to either Superose 6 or TSK-40-XL HPLC columns, while the interaction of the crude glucosylceramidase contained in the water extract of the lysosome mitochondrial fraction of placenta with the two HPLC gel matrices is much weaker. The quite different behaviour of the crude compared to the purified enzyme may be explained by the formation in the crude preparation of associated form(s) of glucosylceramidase with suitable endogenous compound(s), which compete with the gel matrices for the binding to the enzyme. The most likely one component of the enzyme complex is the placental activating factor, previously reported by us (Vaccaro et al. (1985) Biochim. Biophys. Acta 836, 157-166), as indicated by the negligible stimulation of the crude enzyme activity on addition of the factor, either before or after passage through the HPLC columns. On the assumption that the behaviour of crude glucosylceramidase on gel filtration becomes similar to that of the purified enzyme when its interaction with endogenous substance(s) is impaired, we have identified some conditions which prevent the formation of the enzyme associated form(s): (a) the addition of guanidine chloride (0.2 M), a cahotropic agent, to the crude preparation; and (b) the increase of pH up to 8. In conclusion, taking advantage of the anomalous behaviour of glucosylceramidase on gel filtration chromatography, evidence has been obtained that placental glucosylceramidase may occur under several forms which had not been previously reported; a difference in experimental conditions can promote the formation of one or another form, by possibly affecting the composition and/or the stoichiometry and/or the stability of the enzyme complex. PMID- 2248965 TI - Role of anionic lipid in bacterial membranes. AB - The major phospholipids of Bacillus stearothermophilus are phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL). Under the growth conditions used in this study the concentration of anionic lipid (PG + CL) was determined by the pH of the culture medium. Cells grown in a complex medium at pH 5.8, 7.0, and 8.0 contained 17, 29 and 36 nmol of anionic (PG + CL) lipid/mg cell (dry weight). The concentration of the zwitterionic lipid phosphatidylethanolamine (PE) was 17-20 nmol/mg cell (dry weight) under all conditions. Analysis of isolated membrane preparations suggested that the amount of anionic lipid per unit area of membrane increased as the pH of the growth medium was increased. Membranes from cells grown at pH 5.8 and 8.0 contained 130 and 320 nmol anionic lipid/mg membrane protein, respectively. Phosphatidylethanolamine appeared to be localized on the inner membrane surface in cells grown under all conditions. Increasing the ionic strength of the culture medium by the addition of NaCl or KCl had little effect on growth at pH 5.8 but inhibited growth at pH 7 and 8. It was concluded that anionic phospholipid plays an important physiological role in maintaining an acidic pH at the outer membrane surface. PMID- 2248966 TI - Self-associated tetramer of human apolipoprotein E does not lead to its accumulation on a lipid particle. AB - The data of differential measurements of apo E-containing and -free lipid particles in equilibrium binding (J. Biochem. (1989) 105, 582-587) showed complete fit to the calculated curve showing that distribution of apo E among the lipid particles is purely statistical among lipid particles. It was also demonstrated that 5 apo E molecules are required for the saturation of the surface of LDL-size lipid particle in good agreement with 7 +/- 1 given by the binding isotherm. Thus, it is concluded that tetramer formation of apo E in an aqueous phase (J. Biol. Chem. (1985) 260, 16375-16382) does not result in its accumulation on particular lipid particles. PMID- 2248967 TI - Effect of chronic heparin administration on serum lipolytic activity and some aspects of lipid metabolism. AB - Chronic heparin administration to rats for periods up to 8 days by i.p. implantation of mini pumps, increased serum total lipolytic activity in a dose dependent manner up to infusion rates of 10 U/h per 100 g body weight. This augmentation was predominantly due to lipoprotein lipase (LPL). Synchronously, heart muscle demonstrated a dose-dependent reduction in LPL activity and adipose tissue showed a biphasic response, LPL activity decreasing at low doses and rising towards control levels at higher doses. Lipolytic activities of skeletal muscle and liver were unaffected. Increased serum LPL could not be attributed to altered enzyme clearance from the circulation in chronically heparinised rats, but was accompanied by a reduced response to i.v. high-dose heparin indicating reduction in the pool of endothelial-bound enzyme. Fasting serum concentrations of triacylglycerol and glycerol were unaffected in chronically heparinised animals although accelerated clearance of exogenous 14C-labelled VLDL was demonstrated, together with enhanced uptake of the isotope by liver and heart. Since de novo synthesis of fatty acids and triacylglycerol from 3H2O was not increased by heparin, we suggest that serum triacylglycerol concentrations were maintained by enhanced re-esterification of preformed fatty acids taken up by the liver. Hepatic cholesterol synthesis from 3H2O was augmented by heparin; this observation is consistent with reported increases in serum total and HDL cholesterol mediated by chronic heparin administration in man and dog. PMID- 2248968 TI - Eutectic interactions in binary systems containing cholesterol, cholesteryl esters and triacylglycerols. AB - Binary phase behavior of saturated cholesterol esters with trilaurin or cholesterol, and cholesterol with trilaurin, is studied. The existence of specific molecular interactions is detected by comparing the liquidus curve of the eutectic with ideal theory of freezing point depression and correcting the theoretical curve with the Bragg-Williams model when necessary. X-ray data indicate that all eutectic solids are nearly totally fractionated. The phase diagrams are sometimes well-explained by ideal solution theory indicating that polar interactions (e.g., the hydrogen bonding of cholesterol) are much less important than van der Waals interactions between neighboring molecules. However, the hydrogen bonding networks of cholesterol can lead to nonideal solution behavior with other lipids, a phenomenon consistent with previous observations on simpler molecular binaries. An observed nonideal solution behavior of triacylglycerol with cholesterol esters, on the other hand, is unexpected since significant polar interactions are expected to be 'buried' in the predominant nonpolar volume of the molecules involved. PMID- 2248969 TI - Effects of intravenous infusions of commercial fat emulsions (Intralipid 10 or 20%) on rat plasma lipoproteins: phospholipids in excess are the main precursors of lipoprotein-X-like particles. AB - Like most commercial parenteral emulsions, Intralipid contains the same amount of phospholipids (12 mg/ml) to stabilize 100 or 200 mg of soybean oil (10 or 20% formula, respectively). By centrifugation, 10 or 20% Intralipid was separated into a supernatant, fat particles containing the bulk of triacylglycerols stabilized by a fraction of phospholipids and an infranatant--called mesophase- consisting mainly of phospholipids used in excess as emulsifier. We observed that the initial triacylglycerol/phospholipid ratio of the emulsion (100/12 and 200/12, respectively) determines the size of the triacylglycerol-rich particles (260 and 350 nm) as well as the phospholipid content of the mesophase (6.02 and 4.67 mg/ml). To understand the mechanism of the lipoprotein-X (LPX) accumulation generally reported after intravenous fat infusions, plasma lipid levels and lipoprotein profiles were first compared in the rats after infusion (at a constant rate of 0.5 or 1 ml/h for 43 h) of Intralipid 10 or 20%. For the same intravenous triacylglycerol load (100 mg/h), rats infused with Intralipid 10% at 1 ml/h displayed higher triacylglycerol levels than rats infused with the 20% emulsion at 0.5 ml/h, suggesting that the size of exogenous fat particles modulated the catabolic rate of their triacylglycerols. The plasma levels of LPX varied according to the infusion rate of phospholipids not associated with triacylglycerol-rich particles of the emulsion. Moreover, an apo E and apo B enrichment of plasma and an elevation of the apo B48/apo B100 ratio was always observed after Intralipid infusions. In order to confirm that phospholipids of the mesophase are the main LPX precursors, lipoprotein profiles were then compared in the rats after intravenous infusion, at a constant rate of 1 ml/h, of either the mesophase or a suspension of triacylglycerol-rich particles isolated from Intralipid 20%. As expected, significant LPX amounts were only detected in rats infused with the pure mesophase of the emulsion. It was concluded that products of the lipolysis of exogenous fat particles play only a minor role in the formation of LPX. In fact these abnormal lipoproteins are generated by phospholipids of the mesophase which, like infused liposomes, actively mobilize endogenous free cholesterol. Consequently, in order to be considered as true chylomicron models for safe fat delivery in parenteral nutrition and in order to prevent some detrimental effects on cholesterol metabolism, commercial emulsions should be cleared of phospholipid excess. PMID- 2248970 TI - Inhibition of nuclear T3 binding via PLA2-induced release of fatty acids from nuclear membranes. AB - This study was undertaken to explore putative regulatory mechanisms involved in the inhibition of nuclear T3 binding (INB) by fatty acids. Ether extracts of intact rat liver nuclei contained INB-activity. Removement of the nuclear membrane resulted in the loss of INB-activity of the nuclei. Incubation of intact nuclei with phospholipase A2 increased nuclear INB-activity in a time- and dose dependent manner; this was correlated with a rise of free fatty acid concentration in the ether extract. We conclude that fatty acids present in the nuclear membrane can be released by phospholipase A2, and are capable of inhibiting nuclear T3 binding. PMID- 2248971 TI - Characterization of the delta 12 desaturase in the American cockroach, Periplaneta americana: the nature of the substrate. AB - The cockroach, Periplaneta americana, can convert oleic acid (18:1(n - 9], to linoleic acid, (18:2(n - 6], by a microsomal delta 12 desaturase. Most of the desaturase activity was present in the fat body tissue, with lower activity in the epidermis and no detectable activity in the thorax or gut tissue. In incubations of microsomal preparations from fat body tissues with [1-14C]18:1 CoA, increased amounts of [1-14C]18:2 were found with increasing time and protein concentration. The form of the substrate for the delta 12 desaturase was determined to be 18:1-CoA by comparing activity towards [1-14C]18:1-CoA and [1 14C]18:1 transesterified to phospholipid. Ozonolysis of the 18:2 formed from [1 14C]oleoyl-CoA followed by radio-gas-liquid chromatography gave one labeled peak, 9-oxononanoate, which showed that the product of the delta 12 desaturase is the physiologically important isomer, 18:2(n - 6). PMID- 2248972 TI - The relationship between plasma free fatty acids and liver mitochondrial function in vivo. AB - P/O ratio, state 3 and 4 respiration rates, and acceptor control index (ACI) were assessed in rat liver mitochondria following an overnight fast and single bout of treadmill exercise of 30-180 min. P/O was unaffected by fasting and 30 min of exercise; however, ACI was reduced because of an increase in state 4 respiration. Fasting, followed by running for 1 h or more decreased P/O approx. 40% and ACI by 50%, an effect that could be attributed to a reduction in state 3 respiration. The decrease in P/O was reversed 15 min after the cessation of exercise, whereas ACI remained depressed. All these functional alterations were mimicked by incubation of isolated mitochondria with palmitate and reversed by washing them with albumin. No direct correlation between plasma free fatty acids and the alterations in mitochondrial respiration was apparent. These data demonstrate that the decrease in the normal coupling of oxidation and phosphorylation in liver mitochondria produced by fasting/exercise is reversed rapidly in vivo. Furthermore, it is apparent that, if fatty acids act as a regulatory agent under these conditions, they do not do so solely on the basis of their plasma concentration. PMID- 2248973 TI - Lipogenesis in genetically diabetic (db/db) mice: developmental changes in brown adipose tissue, white adipose tissue and the liver. AB - Developmental changes in lipogenesis have been examined in interscapular brown adipose tissue (BAT), epididymal white adipose tissue and the liver of genetically diabetic (db/db) mice and their normal siblings. Lipogenesis was measured in vivo with 3H2O, from weaning (21 days of age) until 20 weeks of age. Hyperinsulinaemia was evident in db/db mice at all ages. Low rates of lipogenesis were observed at weaning in tissues of both groups of mice, but the rate rose rapidly in the first few days post-weaning. In normal mice, peak lipogenesis was obtained in each tissue at 4-5 weeks of age, and there were no major changes (on a whole-tissue basis) thereafter. A different developmental pattern was apparent in db/db mice. The rate of lipogenesis in BAT rose sharply after weaning, reaching a peak at 26 days of age (several times higher than normal mice), and then falling rapidly such that by 45 days of age it was lower than in normal mice; at age 20 weeks lipogenesis in BAT of the diabetic animals was negligible. In white adipose tissue of the db/db mutants lipogenesis (per tissue) reached a maximum at 5 weeks of age, and fell substantially between 10 and 20 weeks of age. Hepatic lipogenesis in the db/db mice rose progressively from weaning until 8 weeks of age, and then decreased. Except at weaning, hepatic lipogenesis (per tissue) was much greater in db/db mice than in normal mice, and the liver was a more important site of lipogenesis in diabetic mice than in normals, accounting for up to 60% of the whole-body total. In contrast, BAT accounted for a considerably smaller proportion of whole-body lipogenesis in db/db mice than in normal mice. It is concluded that there are major developmental differences in lipogenesis between tissues of db/db mice, and between diabetic and normal animals. The data suggest that there is an early and preferential development of insulin resistance in BAT of the db/db mutant. PMID- 2248974 TI - Phosphatidylcholine metabolism for energy production in sea urchin spermatozoa. AB - Sea urchin spermatozoa use endogenous phosphatidylcholine (PC) to produce energy for swimming. The catabolism of PC was studied in Hemicentrotus pulcherrimus spermatozoa. Following incubation in sea water, the content of PC decreased and that of choline increased gradually, whereas phosphocholine maintained a constant level. Measurement of the radioactivity in metabolites converted from 1-palmitoyl 2-[1-14C]linoleoyl-PC, [choline-methyl-14C]dipalmitoyl-PC and 1-[1-14C]palmitoyl lysophosphatidylcholine (LysoPC) showed that the major degradative pathway is PC- --LysoPC----glycerophosphocholine----choline. 1-Palmitoyl-2-[1-14C]linoleoyl-PC and [1-14C]oleic acid were oxidized to 14CO2 in a cell-free system of spermatozoa. Sea urchin spermatozoa thus appear to quite likely obtain energy through the oxidation of fatty acid(s) from PC. PMID- 2248975 TI - Growth-related modulation of human skin fibroblast cholesterol distribution and metabolism. AB - The relationship between cell growth state and the metabolism and distribution of cellular cholesterol was studied in human skin fibroblasts. Cells made quiescent by serum starvation maintained a smaller fraction of total free cholesterol in a pool susceptible to oxidation by added cholesterol oxidase compared to growing cells. The growth-related differences in the distribution of free cholesterol were magnified in cells which were preincubated in low-density lipoprotein. These latter cells hydrolyzed cholesteryl ester which had accumulated in the presence of LDL, resulting in an increased level of cellular free cholesterol after growth activation. By preincubating cells in [3H]cholesterol linoleate-labeled LDL, it could be demonstrated that activation of cell growth facilitated the appearance of LDL-derived cholesterol in a pool accessible to cholesterol oxidase. These studies suggest that onset of growth in fibroblasts leads to a redistribution of free cholesterol from intracellular to plasma membrane compartments. Furthermore, activation of cell growth in cholesterol loaded cells leads to the net conversion of cholesteryl ester to free cholesterol and most of the latter is in the plasma membrane. PMID- 2248976 TI - Purification and properties of new ribosome-inactivating proteins with RNA N glycosidase activity. AB - Ribosome-inactivating proteins (RIPs) similar to those already known (Stirpe & Barbieri (1986) FEBS Lett. 195, 1-8) were purified from the seeds of Asparagus officinalis (two proteins, asparin 1 and 2), of Citrullus colocynthis (two proteins, colocin 1 and 2), of Lychnis chalcedonica (lychnin) and of Manihot palmata (mapalmin), from the roots of Phytolacca americana (pokeweed antiviral protein from roots, PAP-R) and from the leaves of Bryonia dioica (bryodin-L). The two latter proteins can be considered as isoforms, respectively, of previously purified PAP, from the leaves of P. americana, and of bryodin-R, from the roots of B. dioica. All proteins have an Mr at approx, 30,000, and an alkaline isoelectric point. Bryodin-L, colocins, lychnin and mapalmin are glycoproteins. All RIPs inhibit protein synthesis by a rabbit reticulocyte lysate and phenylalanine polymerization by isolated ribosomes and alter rRNA in a similar manner as the A-chain of ricin and related toxins (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). PMID- 2248977 TI - Mammalian liver contains an activity which mimics bacterial chloramphenicol acetyltransferase. AB - Rat liver extracts contain an activity which mimics Escherichia coli chloramphenicol acetyltransferase (CAT); the latter is commonly used to report transcriptional activation of chimeric genes transfected into cultured cells. Although the activities are indistinguishable by the standard thin-layer chromatography assay, alternate methods can discriminate between them. The rat CAT-like activity appears to be an integral membrane protein. It was observed in the microsomal fraction of both liver and kidney. Similarly CAT-like activities were detected in mouse, rabbit and pig liver. In addition, liver homogenates which contain the CAT-like activity also contain a heat-labile inhibitor of (authentic) bacterial CAT. PMID- 2248978 TI - Nucleotide sequence and expression of the isoamylase gene from an isoamylase hyperproducing mutant, Pseudomonas amyloderamosa JD210. AB - The isoamylase gene (ISO) of Pseudomonas amyloderamosa JD210, an isoamylase hyperproducing mutant, was cloned in an isoamylase-deficient and transformable mutant strain K31. By deletion analysis, the ISO gene was found to be located within a 3.3 kilobases BamHI fragment. Its nucleotide sequence contained an open reading frame of 2328 nucleotides (776 amino acids) encoding a secreted isoamylase precursor. The ISO gene fragment was inserted into plasmids pKT230 and pBR 322 in opposite orientations. The expression of the ISO gene in the constructed plasmids was compared in P. amyloderamosa K31, Pseudomonas aeruginosa PAO1-161, Pseudomonas putida mt-2 and Escherichia coli HB101. In all transformed cells, the majority of the isoamylase produced was secreted and higher isoamylase activities were obtained in transformats with the transcriptional direction of the ISO gene similar to the nearby drug-determinant gene of the vector. PMID- 2248979 TI - Characterization of liver-specific expression of rat uricase using monoclonal antibodies and cloned cDNAs. AB - Tissue distribution of uricase (urate oxidase, EC 1.7.3.3) was studied by immunoblotting and RNA slot blot analysis. For immunoblotting, highly specific monoclonal antibodies against rat liver uricase were obtained, and for mRNA detection, a cloned uricase cDNA was used. Among seven tissues studied, uricase was immunologically detected only in the liver. The contents of uricase in other tissues, i.e., brain, thymus, heart, spleen, kidney and lactating mammary gland, were estimated to be less than 2% of that in the liver. Uricase mRNA was also detected only in the liver. The steady-state level of the mRNA in the isolated hepatocytes was relatively constant during the 8-day culture period when compared with those of other mRNAs expressed in the liver, suggesting a unique control mechanism of its expression. PMID- 2248980 TI - Extent of helix perturbation associated with DNA modification by the o-acetyl derivative of the carcinogen 4-hydroxyaminoquinoline-1-oxide. AB - Duplex unwinding associated with DNA modification by 4-acetoxyaminoquinoline-1 oxide, a model ultimate carcinogen of 4-nitroquinoline-1-oxide, has been determined by the agarose gel electrophoresis band-shift method. An average unwinding angle per stable adduct of -15.1 degrees +/- 1.5 degrees for negatively supercoiled topoisomers and -6.5 degrees +/- 1.4 degrees for positively supercoiled topoisomers was obtained. Because of the different proportion of stable adducts (dGuo-N2-AQO, dGuo-C8-AQO, dAdo-N6-AQO) between negatively (8:1.5:0.5) and positively (5:2.5:1) supercoiled topoisomers, the difference in unwinding angles is suggestive of a diverse contribution of the various adducts to the overall conformational change. Since the largest unwinding angle was coupled with the highest proportion of dGuo-N2-AQO adduct, it is likely that this adduct is the most distortive lesion. A contribution of sites of base loss to DNA unwinding was also observed. PMID- 2248981 TI - Sequence analysis of the pig phosphoglucose isomerase gene promoter region. AB - A cDNA for pig phosphoglucose isomerase (PGI) was used to isolate genomic clones representing the 5' portion of the corresponding gene. A total of 656 bases of the pig PGI gene were obtained that include 5'-flanking information and part of exon 1. A major transcription start was localized at 74 nucleotides from the translation start. The sequence organization of the pig PGI promoter is similar to that of other housekeeping genes. This GC-rich region includes a TATA-like box, two putative Sp1 recognition sites but no CCAAT box. PMID- 2248983 TI - [Chemiluminescence in a toluene-fenoxol scintillation system in the radioreceptor method of researching biological membranes]. AB - The scintillation toluene-fenoxol 8/10 system with ammonia (0.01%) is suggested for radioactive counting in radioreceptor biomembrane assay. It is shown that chemiluminescence in this system is defined mainly by membrane components presence. The remotion of filter from scintillator after labelled molecules elution and methanol (3%) addition to scintillation mixture are suggested to reduce the chemiluminescence level. PMID- 2248982 TI - Identification and initial characterization of a fourth leader exon and promoter of the human IGF-II gene. AB - Transcription of the human insulin-like growth factor II (IGF-II) gene is regulated by activation of multiple promoters which act in a tissue-specific and development-dependent manner. Previously, we have identified three different promoters, one of which is active in adult liver tissue only, whereas the other two are active in many fetal tissues and adult non-hepatic tissues. Here we report the identification of a fourth leader exon of the human IGF-II gene indicating the presence of a fourth promoter. Transcription from this promoter yields a 5.0 kb IGF-II mRNA species, which is detected in fetal liver and leiomyosarcoma tissue. PMID- 2248984 TI - [A DNA study of rat liver oligonucleosomes enriched by transcriptionally active genes during induction due to the administration of an amino acid mixture]. AB - A highly active fraction of rat liver oligonucleosome DNA has been isolated and studied by means of thermal denaturation after induction by amino acid mixture or hydrocortisone. A considerable redistribution of DNA content has been shown in sucrose gradient fractions during these forms of induction. The changes are revealed in melting temperature, differential melting profile of DNA, isolated from actively transcribed chromatine fractions. Analysis of melting profiles shows changes of GC content of oligonucleosome DNA, suggesting that there are differences in activation during two studied forms of induction. PMID- 2248985 TI - [The action of long-wave ultraviolet light on the body]. AB - A review of data obtained lately on the effect of ultraviolet radiation (lambda greater than 280 nm) on organism is given. The role of oxidative processes and first of all of photo lipid peroxidation of biomembranes in developing of a number of effects due to UV radiation are considered. PMID- 2248986 TI - [The negative shift in the reversal potential of the acetylcholine-induced incoming current in the RPa3 and LPa3 neurons of the edible snail during its extinction]. AB - A negative shift of reversal potential at its extinction has been found with the current-voltage relation of acetylcholine-induced inward current in Helix lucorum's RPa3 and LPa3 neurons. An assumption has been made on a nonuniform extinction of acetylcholine-induced currents which is due to the motion of different ions. Ion flow with a more positive equilibrium potential decreases to a greater degree than reversal potential. It can be a current of Ca2+ and/or Na+ ions. PMID- 2248987 TI - [The dynamic excitability of the hypothalamic nuclei in the cat in relation to the degree of thirst]. AB - The increase of excitement of lateral and supraoptic nuclei of hypothalamus in cats on the background of thirsty rate has been established to appear under the influence of shifts in blood physical and chemical properties and via irritation of specific visceral receptors reflectively as well. PMID- 2248988 TI - Dynamics of oxygen unloading from sickle erythrocytes. AB - The objective of this work is to theoretically model oxygen unloading in sickle red cells. This has been done by combining into a single model diffusive transport mechanisms, which have been well-studied for normal red cells, and the hemoglobin polymerization process, which has been previously been studied for deoxyhemoglobin-S solutions and sickle cells in near-equilibrium situations. The resulting model equations allow us to study the important processes of oxygen delivery and polymerization simultaneously. The equations have been solved numerically by a finite-difference technique. The oxygen unloading curve for sickle erythrocytes is biphasic in nature. The rate of unloading depends in a complicated way on (a) the kinetics of hemoglobin S polymerization, (b) the kinetics of hemoglobin deoxygenation, and (c) the diffusive transport of both free oxygen and oxy-hemoglobin. These processes interact. For example, the hemoglobin S polymer interferes with the transport of both free oxygen and unpolymerized oxy-hemoglobin, and this is accounted for in the model by diffusivities which depend on the polymer and solution hemoglobin concentration. Other parameters which influence the interaction of these processes are the concentration of 2,3-diphosphoglycerate and total hemoglobin concentration. By comparing our model predictions for oxygen unloading with simpler predictions based on equilibrium oxygen affinities, we conclude that the relative rate of oxygen unloading of cells with different physical properties cannot be correctly predicted from the equilibrium affinities. To describe the unloading process, a kinetic calculation of the sort we give here is required. PMID- 2248989 TI - Schwan equation and transmembrane potential induced by alternating electric field. AB - The transmembrane potential generated by an alternating electric field (ac) depends strongly on the frequency of the field and can be calculated using the Schwan Equation. We have measured the critical electric breakdown potential, delta psi crit, of the plasma membrane of murine myeloma cell line (Tib9) using ac fields, by monitoring the entry of a fluorescence probe, propidium iodide, into the cells. This dye is weakly fluorescent in solution but becomes strongly fluorescent when it binds to DNA. Experiments were done under a microscope by direct visual examination of single cells or by examining photographic prints. When an ac field reached the intensity, Ecrit, that generated a maximal membrane potential delta psi max, equal to or greater than the delta psi crit, the membrane was perforated at the two loci facing the electrodes. The dye diffused into the cell, giving rise to two bright, narrow bands, which expanded to the whole cell in 1-3 min. delta psi crit's were measured in three media of different resistivities, rho ext, (52,600, 7,050, and 2,380 omega cm), over the range of 0.1-300 kHz, with the field duration of 200 ms. Regression analysis based on the Schwan Equation showed that in a medium of given resistivity, the delta psi crit was constant over the frequency range studied. When the capacitance of the membrane, Cmembr, was taken to be 0.90 microF cm-2, the resistivity of the cytoplasmic medium, rho int, was determined to be 910-1,100 omega cm. The delta psi crit were 0.33, 0.48, and 0.53 V, respectively, for the three media in decreasing resistivities. The good fit of these data to the curves calculated using the Schwan Equation indicates that the equation may be used to describe the transmembrane potential of a living cell generated by an oscillating electric field. PMID- 2248990 TI - Monomer diffusion into polymer domains in sickle hemoglobin. AB - The gelation of sickle hemoglobin includes the formation of spherulitic arrays of polymers, known as polymer domains, which are an intrinsic result of the polymer formation mechanism. We have observed the diffusion of monomers into domains as they form, which substantially increases the total concentration of hemoglobin within the domain. The maximum total concentration attained is comparable with the pellet concentration of 0.5-0.55 g/cm3 obtained in sedimentation experiments. The half time for this process is approximately 50 s for domains of 25 microns radius, and is approximately independent of temperature. The shape of the diffusion progress curves as well as the deduced diffusion constants, and their weak temperature dependence are consistent with a simple model of hemoglobin monomer diffusion into the domain. PMID- 2248991 TI - Fluorescence lifetime distributions in human superoxide dismutase. Effect of temperature and denaturation. AB - The internal dynamics of human superoxide dismutase has been studied using time resolved fluorescence. The fluorescence decay has been analyzed using continuous distribution of lifetime values. The effect of temperature and conformational state on the lifetime distribution has been investigated. The emission of the single tryptophan residue depends on the nature and dynamics of the protein matrix. Conformational changes have been induced by increased concentration of guanidinium hydrochloride. We found that both temperature and conformation strongly effect the width of the lifetime distribution. PMID- 2248992 TI - Quantification of transport and binding parameters using fluorescence recovery after photobleaching. Potential for in vivo applications. AB - Fluorescence Recovery After Photobleaching (FRAP) has been used extensively in the study of transport and binding in biological media in vitro. The present study adapts and further develops FRAP so that it may be utilized for the in vivo quantification of binding parameters. The technique is validated in vitro by measuring mass transport and binding parameters for the Concanavalin A/Mannose binding system (a diffusion-limited system). The pseudo-equilibrium constant (the product of the equilibrium constant and the total concentration of binding sites) for this system was determined to be 26 +/- 15 which compares favorably with literature values ranging between 16 and 32. The applicability of this technique to measure parameters for monoclonal antibody/antigen interactions in a thin tissue preparation such as the rabbit ear chamber tissue preparation is also examined. Unlike other methods for measuring binding parameters, this is the only technique which has the potential to measure parameters relevant to antibody delivery in vivo. The proposed technique is noninvasive and does not require a priori knowledge of, independent measurement of, or variation in the concentration of binding sites or total concentration of binding species. PMID- 2248993 TI - Membrane fluidity changes of liposomes in response to various odorants. Complexity of membrane composition and variety of adsorption sites for odorants. AB - Three kinds of liposomes prepared from phosphatidylcholine (PC), azolectin, and azolectin-containing membrane proteins of the canine erythrocytes were used as models for olfactory cells. To explore properties of the adsorption sites of odorants, membrane fluidity changes in response to various odorants were measured with various fluorescence dyes which monitor the fluidity at different depths and different regions of the membranes. (a) Application of various odorants changed the membrane fluidity of azolectin liposomes. The patterns of membrane fluidity changes in response to odorants having a similar odor were similar to each other and those in response to odorants having different odors were different from each other. These results suggested that odorants having a similar odor are adsorbed on a similar site and odorants having different odors are adsorbed on different sites. (b) Such variation of the pattern was not seen in liposomes of a simple composition (PC liposome). (c) In the proteoliposomes whose composition was more complex than that of azolectin liposomes, the patterns of membrane fluidity changes varied among odorants having a similar odor. It was concluded that liposomes of complex membrane composition have the variety of adsorption sites for odorants. PMID- 2248994 TI - Study of mechanisms of electric field-induced DNA transfection. II. Transfection by low-amplitude, low-frequency alternating electric fields. AB - Electroporation for DNA transfection generally uses short intense electric pulses (direct current of kilovolts per centimeter, microseconds to milliseconds), or intense dc shifted radio-frequency oscillating fields. These methods, while remarkably effective, often cause death of certain cell populations. Previously it was shown that a completely reversible, high ionic permeation state of membranes could be induced by a low-frequency alternating electric field (ac) with a strength one-tenth, or less, of the critical breakdown voltage of the cell membrane (Teissie, J., and T. Y. Tsong. 1981. J. Physiol. (Paris). 77:1043-1053). We report the transfection of E. coli (JM105) by plasmid PUC18 DNA, which carries an ampicillin-resistance gene, using low-amplitude, low-frequency ac fields. E. coli transformants confer the ampicillin resistance and the efficiency of the transfection can be conveniently assayed by counting colonies in a selection medium containing ampicillin. For the range of ac fields employed (peak-to-peak amplitude 50-200 V/cm, frequency 0.1 Hz-1 MHz, duration 1-100 s), 100% of the E. coli survived the electric field treatment. Transfection efficiencies varied with field strength and frequency, and as high as 1 x 10(5)/micrograms DNA was obtained with a 200 V/cm square wave, 1 Hz ac field, 30 s exposure time, when the DNA/cell ratio was 50-75. Control samples gave a background transfection of much less than 10/micrograms DNA. With a square wave ac field, the transfection efficiency showed a frequency window: the optimal frequency was 1 Hz with a 200 V/cm field, and was approximately 0.1 Hz with a 50 V/cm field. Transfection efficiency varied with the waveform: square wave > sine wave > triangle wave. If the DNA was added after the ac field was turned off, transfection efficiency was reduced to the background level within 1 min. The field intensity used in this study was low and insufficient to cause electric breakdown of cell membranes. Thus, DNA transfection was not caused by electroporation of the cell membranes. Other possible mechanisms will be considered. PMID- 2248995 TI - Chemotaxis of bacteria in glass capillary arrays. Escherichia coli, motility, microchannel plate, and light scattering. AB - Random and directed motility of bacterial populations were assayed by monitoring the flux of bacteria through a microchannel plate (a porous glass plate comprising a fused array of capillary tubes) separating two identical stirred chambers. Cells, washed free of growth medium by a new filtration method, were added to one chamber at a low density. Their number in the other chamber was determined from the amount of light scattered from a beam of a laser diode and recorded on a strip chart. Diffusion coefficients were computed from fluxes observed in the absence of chemical gradients, and chemotaxis drift velocities were computed from fluxes observed in their presence. Cells migrated through tubes of diam 10 microns more rapidly than through tubes of diam 50 microns, suggesting that the straight segments of their tracks were aligned with the axes of the smaller tubes. Mutants that are motile but nonchemotactic could be selected because they move through the microchannel plate in the face of an adverse gradient. Weak chemotactic responses were assessed from ratios of fluxes observed in paired experiments in which the sign of the gradient of attractant was reversed. Studies were made of wild-type Escherichia coli and mutants that are nonmotile, tumblely, smooth-swimming, aspartate-blind, or defective in methylation and demethylation. Chemotaxis drift velocities for the latter mutants (cheRcheB) were quite small. PMID- 2248996 TI - Subpicosecond resonance Raman spectroscopy of carbonmonoxy- and oxyhemoglobin. AB - In this paper we present the resonance Raman spectrum of the carbonmonoxy- (HbCO) and oxyhemoglobin (HbO2) photointermediates on a 800-900 fs timescale. In the case of HbCO, the frequencies of the so-called core-size markers (1500-1650 cm-1) are characteristic of a deoxylike photoproduct in a high spin state (S = 2) with a partially domed heme. The spectrum of the HbO2 photointermediate, on the other hand, is different, and may be characteristic of an excited-state species. These results are discussed in terms of a reaction scheme previously presented by Petrich, J. W., C. Poyart, and J. L. Martin (1988. Biochemistry. 27:4049-4060) and compared with those obtained in the literature on a 30-40 ps timescale. In both molecules a distinct downshift of the v4 mode was observed with respect to the equilibrium value, which is indicative of an elevated temperature of the heme after photodissociation. PMID- 2248997 TI - Electrostatic properties of fiber cell membranes from the frog lens. AB - The electrostatic properties of lens fiber cell membranes have been investigated by recording the electrophoretic mobility of membrane vesicles formed from isolated fiber cells. The vesicles appear to be sealed and have external surfaces that are representative of the extracellular surface of fiber cells. The average mobility of a vesicle in normal Ringer's solution was 0.9 microns/s per v/cm, which gives a zeta potential of -9 mV, a value similar to that reported for other cells (McLaughlin, S. 1989. Annu. Rev. Biophys. Biophys. Chem. 18:113-136.). There was no significant difference in the mobility of vesicles formed from peripheral, middle cortical, or nuclear fiber cells. Vesicle surface changes were titrated using Ca and Mg and each had a pK of approximately 2, which is similar to that for the most common phospholipids. We also titrated these charges with varying pH and found the most significant changes in mobility at pH values between 5 and 6. The majority of lipids found in biological membranes are not titratable in this pH range, so the pH effect is probably through a membrane protein charged group. These experimental data in conjunction with the previously measured extracellular voltage gradient (Mathias, R. T., and J. L. Rae. 1985. Am. J. Physiol. 249:C181-C190) imply that electroosmosis can generate a fluid velocity of approximately 0.6 mm/h, directed from the aqueous or vitreous toward the center of the lens, along intercellular clefts. PMID- 2248998 TI - Dynamic motions of 1,6-diphenyl-1,3,5-hexatriene in interdigitated C(18):C(10)phosphatidylcholine bilayers. AB - This study investigates the dynamic behavior of 1,6-diphenyl-1,3,5-hexatriene (DPH) in C(18):C(10)phosphatidylcholine [C(18):C(10)PC] bilayers. C(18):C(10)PC is an asymmetric mixed-chain phosphatidylcholine known to form mixed interdigitated structures below the transition temperature and form partially interdigitated bilayers above the transition temperature. The rotation of DPH in C(18):C(10)PC has been described in terms of the thermal coefficient of rotation using the modified Y-plot method which takes into account the limiting anisotropy value. During the phase transition of C(18):C(10)PC, DPH exhibits a thermal coefficient b2M = 0.41 - 0.51 degrees C-1 which is similar to the b2M values obtained with noninterdigitated phosphatidylcholine bilayers. Differential polarized phase-modulation fluorometry has also been employed to study the dynamic behavior of DPH in C(18):C(10)PC in real time. The data show that DPH contains considerable motion in the highly ordered mixed interdigitated bilayers. The DPH motion steadily increases with an increase in temperature as shown by the rotational correlation time, and the wobbling diffusion constant. However, the limiting anisotropy, the order parameter, and the width of the lifetime distribution undergo an abrupt decrease, and a corresponding abrupt increase in the cone angle, at approximately 16 degrees C. This temperature range is near the onset temperature of the phase transition as determined by differential scanning calorimetry. The rotational parameters show strong hysteresis on heating and cooling. All the rotational parameters derived from DPH fluorescence in mixed interdigitated C(18):C(10)PC exhibit magnitudes similar to those obtained from non interdigitated gel phases of symmetric diacylphosphatidylcholines. These results, combined with those obtained with dehydroergosterol (Kao, Y. L., P. L. G. Chong, and C. Huang. 1990. Biochemistry. 29:1315-1322), suggest that considerable rotational mobility of small molecules can be sustained in an intramolecularly highly ordered interdigitated lipid matrix, implying that the membrane maintains a fluid environment around membrane perturbants even when the lipid matrix is extensively interdigitated. PMID- 2248999 TI - Michaelis-Menten equation for an enzyme in an oscillating electric field. AB - The electric charges on an enzyme may move concomitantly with a conformational change. Such an enzyme will absorb energy from an oscillating electric field. If in addition the enzyme has a larger association constant for substrate than for product, as is often true, it can use this energy to drive the catalyzed reaction away from equilibrium. Approximate analytical expressions are given for the field driven flux, electrical power absorbed, free-energy produced per unit time, thermodynamic efficiency, and zero-flux concentrations. The field-driven flux is written as a generalized Michaelis-Menten equation. PMID- 2249000 TI - Elastic deformation and failure of lipid bilayer membranes containing cholesterol. AB - Giant bilayer vesicles were reconstituted from several lipids and lipid/cholesterol (CHOL) mixtures: stearolyloleoylphosphatidylcholine (SOPC), bovine sphingomyelin (BSM), diarachidonylphosphatidylcholine (DAPC), SOPC/CHOL, BSM/CHOL, DAPC/CHOL, and extracted red blood cell (RBC) lipids with native cholesterol. Single-walled vesicles were manipulated by micropipette suction and several membrane material properties were determined. The properties measured were the elastic area compressibility modulus K, the critical areal strain alpha c, and the tensile strength tau lys, from which the failure energy or membrane toughness Tf was calculated. The elastic area expansion moduli for these lipid and lipid/cholesterol bilayers ranged from 57 dyn/cm for DAPC to 1,734 dyn/cm for BSM/CHOL. The SOPC/CHOL series and RBC lipids had intermediate values. The results indicated that the presence of cholesterol is the single most influential factor in increasing bilayer cohesion, but only for lipids where both chains are saturated, or mono- or diunsaturated. Multiple unsaturation in both lipid chains inhibits the condensing effect of cholesterol in bilayers. The SOPC/CHOL system was studied in more detail. The area expansion modulus showed a nonlinear increase with increasing cholesterol concentration up to a constant plateau, indicating a saturation limit for cholesterol in the bilayer phase of approximately 55 mol% CHOL. The membrane compressibility was modeled by a property-averaging composite theory involving two bilayer components, namely, uncomplexed lipid and a lipid/cholesterol complex of stoichiometry 1/1.22. The area expansion modulus of this molecular composite membrane was evaluated by a combination of the expansion moduli of each component scaled by their area fractions in the bilayer. Bilayer toughness, which is the energy stored in the bilayer at failure, showed a maximum value at approximately 40 mol% CHOL. This breakdown energy was found to be only a fraction of the available thermal energy, implying that many molecules (approximately 50-100) may be involved in forming the defect structure that leads to failure. The area expansion modulus of extracted RBC lipids with native cholesterol was compared with recent measurements of intact RBC membrane compressibility. The natural membrane was also modeled as a simple composite made up to a compressible lipid/cholesterol matrix containing relatively incompressible transmembrane proteins. It appears that the interaction of incompressible proteins with surrounding lipid confers enhanced compressibility on the composite structure. PMID- 2249001 TI - The effect of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide on glucose removal in the anaesthetized rat and on insulin secretion from rat pancreatic islets in vitro. AB - The effect of intravenous infusion of islet amyloid polypeptide (IAPP/amylin) and calcitonin gene-related peptide (CGRP) on blood glucose and plasma insulin in the basal and glucose-stimulated state was investigated in the anaesthetized rat. Both peptides had no effect on basal blood glucose or plasma insulin but following an intravenous bolus of glucose, CGRP-treated rats were hyperglycaemic and hyperinsulinaemic compared with control animals which were similar to IAPP treated rats. IAPP had no effect on glucose-stimulated islet insulin secretion. These results suggest that CGRP, but not IAPP, alters glucose removal in vivo. PMID- 2249002 TI - Semliki Forest virus induced cell-cell fusion at neutral extracellular pH. AB - Semliki Forest virus-induced cell-cell fusion from within was considered to exclusively occur at mildly acidic pH (less than 6.2). Data of this study show that such cell fusion can also be triggered by transient acidification of the cytoplasm of infected cells at an extracellular, neutral pH. Results were obtained by utilizing NH4Cl pulses combined with covalent modification of cell surface proteins. The observation implies a revision of the current consensus regarding the mechanism of Semliki Forest virus induced cell-cell fusion. We propose a model in which at least two peptide segments of the viral spike protein E1 may be involved in triggering the fusion event. PMID- 2249003 TI - Inhibition of protein kinase C by oxidation products of retinol. AB - Retinol has little effect on the activity of protein kinase C. However, air oxidation of retinol produces products which are inhibitory to this enzyme. These results are consistent with a suggestion that the activity of protein kinase C is modulated by the bulk biophysical properties of its environment. The facile susceptibility of retinol to oxidation, as demonstrated by HPLC analysis, explains some of the discrepant reports of its effects on the activity of protein kinase C. PMID- 2249005 TI - A predictive model for life expectancy curves. AB - Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable. PMID- 2249004 TI - Purification of thymocyte growth peptide (TGP) from sheep thymus. Relationship to FTS/thymulin. AB - Thymocyte growth peptide (TGP) initiates DNA synthesis in immature thymocytes and has previously been characterized as an acidic peptide isolated from calf thymus. We now report the isolation of TGP from sheep thymus and show it to be a nonapeptide with a large N-terminal blocking moiety characterized by high UV absorbance. The amino acid composition is identical to FTS, consisting of 2 Gly, 2 Ser, 2 Glx, 1 Ala, 1 Lys, 1 Asx. In contrast to FTS, TGP is acidic with an apparent isoelectric point of 4.2 and a high UV absorbance at 270-280 nm. Reverse phase chromatography of TGP at an acidic pH results in a change of the molecule and the appearance of two new compounds TGP-A and TGP-B, both with less than 50% of the original TGP activity. Full activity could be restored by the addition of ZnCl2 to TGP-A. Both TGP-A and B have some amino acid composition and high UV absorbance as native TGP. We propose that TGP consists of a non-peptide moiety bound to the N-terminal of the nonapeptide Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn and that the active molecule is stabilized by Zn2+. PMID- 2249006 TI - Does a cell perform isoelectric focusing? AB - A model of intracellular electrical sorting of enzymes and organelles in the cytosol, based on isoelectric focusing, is proposed. The focusing is suggested to take place over a centrally symmetric pH gradient which in the cytosol of the yeast Saccharomyces cerevisiae is known to be 7.2-6.4. From published data on the energetic capacity and from the computed electric resistance of the S. cerevisiae cell, the maximum value of the electric field that can be maintained in the cytosol was estimated. The results showed that the strength of a centrally symmetric intracytosolic electric field could be as high as 90 mV/cm, which is sufficient to account for sorting of cytosolic proteins according to their isoelectric points. Although direct experimental evidence for intracellular isoelectric focusing is still missing, several phenomena of physiological importance can be understood on the assumption of its real existence. PMID- 2249007 TI - Interrelationships among major protistan groups based on a parsimony network of 5S rRNA sequences. AB - To test the validity of the maximum parsimony approach to discern protistan interrelationships, we have derived an optimal network of 16S-like rRNA sequences using our parsimony algorithm and compared it with those reported using the distance matrix method. We have also derived an optimal network topology of 50 5S rRNA sequences through an interactive search using our algorithm. In both these networks, the kinetoplastids and euglenoids form a linkage group with Dictyostelium emerging from its neighbourhood. The cryptophytes, dinoflagellates and chromophytes and green algae emerge as independent lines suggesting that plastids arose more than once during protistan evolution. The large 5S rRNA tree further indicates independent origins of mesozoa and metazoa; kinetoplastids and ciliates; and diphyletic origin of fungi. Comparatively close positions of charales and land plants, chytrids and Zygomycetes, Physarum and amoeba, and red algae and green algae are also seen in this network. PMID- 2249009 TI - Chromosomal evolution in Cervidae. AB - On the basis of chromosome data obtained on 30 species and 20 subspecies of Cervidae, a report is submitted on the karyosystematics of this family. The primitive karyotype of Cervidae may be inferred to be composed of 35 acrocentric pairs (2n = 70 FN = 70). During the phyletic evolution of this family different types of chromosome rearrangements were probably selected and the group may have differentiated karyologically into three branches: (1) the Cervinae that fixed a centric fusion resulting in a metacentric pair of autosomes (2n = 68, FN = 70), as shown by the basic karyotype of Cervus elaphus, and where Robertsonian fusions are the preeminent type of chromosome rearrangement; (2) the Odocoileinae, in which pericentric inversions and Robertsonian fusions were favored, yielding first a submetacentric X and then a submetacentric autosome pair. The most representative karyotype is 2n = 70, FN = 74--as in Odocoileus hemionus; and (3) the Muntiacinae, in which centric and tandem fusions were the most common chromosome rearrangements. While Muntiacus reevesi has a karyotype 2n = 46, FN = 46, the chromosome number drops down to 2n = 6 in the females of the M. muntjak vaginalis subspecies group and M. rooseveltorum. Therefore, while the karyotypes are conserved within the subfamilies Cervinae and Odocoileinae; the subfamily Muntiacinae appears to be the most chromosomally diversified group. The few karyological data on the Moschus berezovskii suggest that the Moschinae should be placed in a separate family, the Moschidae. PMID- 2249008 TI - Characterization of nuclear DNA in 12 species of Chlorella (Chlorococcales, Chlorophyta) by DNA reassociation. AB - Strains of 12 different species of the genus Chlorella were analyzed for amount, reiteration frequency and kinetic complexity of chromosomal DNA components by C0t analysis. The resulting C0t curves reveal at least two different DNA components consisting of single copy DNA (up to 95%) and of repetitive DNA with complexities of 4.1 x 10(3) base pairs (bp) to approximately 11.7 x 10(3) bp and a reiteration frequency of 100-760. The total amount of repetitive DNA is less than 9% of the nuclear genome and similar in all strains studied. In contrast, the total kinetic complexity varies in a wide range from 1.26 x 10(7) bp to 8.08 x 10(7) bp which is mainly due to differences in the size of single copy DNA. The genome sizes in Chlorella seem not to be correlated with biochemical and physiological characteristics and therefore are unlikely to be useful as a taxonomical marker. A comparison of thermal denaturation profiles showed that the melting points of repetitive and single copy DNA differ by approximately 7 degrees C which may result from base mismatch and/or from a distinct base composition of the repetitive DNA. PMID- 2249010 TI - Experiments with a universe for molecular modelling of biological processes. AB - A computer simulation program and results of preliminary simulations of an abstract two-dimensional universe are presented, in which biological and physical processes can be modelled at the molecular level. Two types of permanent elements (atoms) occupy squares of the universe: called 0 and 1. Atoms sharing a common square form a particle, with properties determined by its component atoms. Atoms, particles, and complexes of particles move and collide according to rules like those of classical mechanics. At a higher level of organization, the string of atoms in a particle is viewed as a program, whose execution can affect the space around the particle. The computer program (written in Turbo-Pascal language) can simulate the evolution of the universe starting from any given initial configuration of the particles. Three examples of simulations, showing the development of ordered spatial structures from initial sets of randomly distributed particles, illustrate the universe's potential in modelling various molecular processes. PMID- 2249011 TI - [Randomized trial of initial chemotherapy in 151 locally advanced carcinoma of the cervix (T2b-N1, T3b, MO)]. AB - From 1982 to 1987, a randomized phase III trial was performed in order to determine the long-term effect of induction chemotherapy before standard pelvic irradiation in stage IIb-N1, III squamous cell carcinomas of the cervix. Patients were randomized to either chemotherapy and radiotherapy (C + R group) vs radiotherapy alone (R group). Radiotherapy for all patients consisted of 50 Gy in the pelvis with a boost by external irradiation or by brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen was an association of methotrexate (10 mg/m2, D2-4), chlorambucil (4 mg/m2, D1-5), vincristine (0,7 mg/m2, D1), cisplatin (80 mg/m2, D5), given every 3 wks; at least 2 courses were to be given before assessing efficacy and 2 more courses were given to patients who responded. One hundred and fifty-one patients were fully evaluable, after a mean follow-up of 38 mths (range 2-7 years), 76 in the R arm and 75 in the C + R arm. The response rate (greater than 50%) to chemotherapy was 42.5%. After completion of treatment, the complete response rate was 86.8% in the R arm and 86.3% in the C + R arm. The 3 year disease-free survival was 58.7% in the C + R group and 54.5% in the R group, and the median survival was 39.5% and 47 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group (when chemotherapy had been active) than in the R group (p = 0.04). Although radiotherapy was not modified whether patients had initial chemotherapy or not, tolerance was not significantly different between the 2 groups. The data collected in this study indicate that: 1) efficacy of induction chemotherapy is the only available predictive test for long-term results, 2) tolerance to treatment is crucial for optimal chemotherapy delivery, 3) higher dose intensity of chemotherapy in cervical carcinoma is associated with a better tumor reduction, and probably a better survival. PMID- 2249012 TI - [Distal metastases of bronchial cancers. Bone and soft tissue metastases]. AB - Distal metastases are classically situated below the knee or elbow. However, metastases of the extremities: wrist and hand, or ankle and foot, have etiological and histological characteristics. We report one case of bone metastasis and one case of soft tissue metastasis. The distal bone metastases are often solitary. Bronchial cancers represent the most frequent cause of distal metastases (20% of all cases). They are responsible for 50% of distal metastases of the upper limb and more often occurs as a squamous cancer. Their localization may sometimes reveal a bronchial cancer, and so allow curative surgery. The metastases of soft tissue are exceptional. In the literature, only 2 cases of soft tissue metastasis of bronchopulmonary cancer are described. Clinically, it is a painful swelling preserving the under lying bone. The prognosis is always one of bronchial metastasis cancer with an average survival of 3-6 months. PMID- 2249013 TI - High BCM serum levels in patients with non breast tumors: first results. PMID- 2249014 TI - [Treatment of advanced cancer of the breast with FEC polychemotherapy using epirubicin at 75 mg/m2 dose (FEC 75)]. PMID- 2249015 TI - [Multidisciplinary consultation. A diagnosis of AIDS]. PMID- 2249016 TI - [Hodgkin's disease in developing countries]. AB - The presentation of Hodgkin's disease (HD) is not the same in western countries and in developing countries. In the latter HD remains a severe disease partly because of a delayed diagnosis. Pathology is less favorable, stages are more advanced. Young patients are even more afflicted. Despite difficulties to treat patients, oncologists have to move to treat as well as possible potentially curable disease in order to save many years of active life. HD would be a good model to promote multidisciplinary centers where patients could be cared and cured in the best conditions. PMID- 2249017 TI - [Prognostic value of thymidine kinase in cancer of the breast]. AB - We have measured by a radioenzymatic assay the thymidine kinase in the cytosol of 182 primary infiltrating breast cancers. Maximal follow-up is 95 months. Thymidine kinase was found to be related to SBR grade, tumour size and absence of oestradiol receptors (RE). Univariate analysis has pointed out a significant linkage between overall or metastase free survival and thymidine kinase, using a cut-off level of 80 mU/mg protein which is the most discriminating value. Thymidine kinase appeared to be particularly useful in lymph-node-positive, RE negative and grade 3 patients. Multivariate analysis of the overall survival and of the metastase free survival (Cox model) revealed that they were strongly related to thymidine kinase status. PMID- 2249018 TI - [Sensitivity and specificity of the determination of urinary catecholamines and their acid metabolites in the diagnosis of neuroblastoma in children]. AB - A retrospective comparison of urinary excretion of norepinephrine, epinephrine, dopamine and/or their acidic metabolites, HVA and VMA, in 36 children with neuroblastoma versus 360 hospitalized children without neuroblastoma showed a sensibility of 72% and a specificity of 98% for HVA and 80% and 97% for VMA respectively. Consequently, the sensibilities and specificities of these 2 determinations confirm their useful purpose for the biochemical diagnosis of neuroblastoma in preference to the determinations of norepinephrine, epinephrine and dopamine. PMID- 2249019 TI - Phase II study of epirubicin in advanced soft tissue sarcoma. AB - Thirty-seven patients (pts) with previously untreated and measurable advanced soft tissue sarcoma entered this phase II study: 22 men and 15 women were included. Median age was 58 (range: 20-71). The starting dose of epirubicin was 100 mg/m2 IV bolus every 3 wks. In the case of minimal myelosuppression, the dose was increased by 10 mg/m2 to 130 mg/m2 (Mean dose per cycle: 105 mg/m2). Median cumulative dose of epirubicin administered was 445 mg/m2 (range: 200-1320 mg/m2). From 32 evaluable pts, one had a complete response (CR), 5 a partial response (PR), (CR + PR = 18.7% +/- 13.8%), 12 showed no change (37.5%) and 14 had progressive disease. The number of complete or partial responses observed was not modified by increasing the doses of epirubicin. Median time to progression was 4 months. From 32 pts evaluable for toxicity, hematologic toxicity at d 21 was mild. Non hematological toxicities consisted of nausea and vomiting in 74% of pts (WHO grade 3 = 5%), stomatitis in 12.2% (WHO grade 3 = 3%) and alopecia in 91% (WHO grade 2-3 = 72%). No cardiac dysfunction was recorded during the treatment, even though 7 patients received more than 800 mg/m2 of epirubicin (median: 850 mg/m2, range: 810-1320 mg/m2). The results of this study show that epirubicin is an active drug in advanced soft tissue sarcoma. PMID- 2249020 TI - Early diagnosis of acute myocardial infarction. PMID- 2249021 TI - Flat feet in children. PMID- 2249022 TI - Forensic pathology: a blinkered report. PMID- 2249023 TI - Ultrasonography in the diagnosis of renal obstruction. PMID- 2249024 TI - Aerobic work capacity in patients with chronic fatigue syndrome. AB - OBJECTIVE: To determine the aerobic work capacity of patients with the chronic fatigue syndrome and compare it with that of two control groups, and to assess the patients' perception of their level of activity before and during illness. DESIGN: A symptom limited exercise treadmill test with on line gas analysis and blood sampling was used. Subjects were assessed by one investigator, who was blind to the group which they were in. SETTING: Department of medicine, Royal Victoria Hospital, Belfast. SUBJECTS: 13 Patients (10 women, three men) who fulfilled the diagnostic criteria for chronic fatigue syndrome. Two control groups of similar age, sex, and body weight: 13 normal subjects (10 women, three men) and seven patients (five women, two men) with the irritable bowel syndrome. MAIN OUTCOME MEASURES: Aerobic work capacity as assessed by several variables such as length of time on treadmill, heart rate, and biochemical measurements; Borg score; and visual analogue scores of perceived level of physical activity. RESULTS: The patients with the chronic fatigue syndrome had a reduced exercise capacity compared with that of the other subjects, spending a significantly shorter time on the treadmill. They had a significantly higher heart rate at submaximal levels of exertion and at stage III exertion had significantly higher blood lactate concentrations. Using a Borg score, they showed a significantly altered perception of their degree of physical exertion with a mean score of 8.2 compared with 6.6 and 5.3 for the normal subjects and patients with the irritable bowel syndrome respectively. Using a visual analogue scale they indicated that they had a greater capacity for activity before illness than had the patients with the irritable bowel syndrome, but the scores were not significantly different between the two groups. Both groups of patients indicated reduced activity at the time of testing. Normal controls and patients with the irritable bowel syndrome aspired to a greater level of activity than their current level, but the patients with the chronic fatigue syndrome aspired to a level similar to that which they had had before their illness. CONCLUSIONS: Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity. PMID- 2249025 TI - Effects of discrimination by sex and race on the early careers of British medical graduates during 1981-7. AB - OBJECTIVE: To examine the possible effects of discrimination by sex and race on the career patterns of doctors up to six years after qualifying. DESIGN: Postal questionnaire follow up survey. PARTICIPANTS: 1572 Doctors who graduated from five British medical schools in 1981, 1983, and 1985, including 587 women and 131 doctors from ethnic minorities. MAIN OUTCOME MEASURES: Reported success rates of applications for training posts. RESULTS: Comparison of the career patterns of women and men yielded no evidence of discrimination against women in competition for posts. In contrast, there were striking differences in career patterns between graduates of native European origin and those of ethnic minority origin. Graduates from ethnic minorities reported lower success rates and more difficulty in obtaining house officer posts, registrar posts, and places in vocational training schemes in general practice. Most of this discrimination seemed to occur at the stage of shortlisting for interview. Graduates from ethnic minorities were more likely than graduates of native European origin to have experienced spells of unemployment while seeking work. They were also more likely to have changed their original choice of career because of difficulty in obtaining suitable training posts or unfavourable career prospects. CONCLUSIONS: Discrimination against ethnic minorities occurs in the competition for training posts among graduates from British medical schools. There was no evidence of discrimination against women graduates. Shortlisting procedures based on objective scoring systems may help to ensure equality of opportunity in future. PMID- 2249026 TI - Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. AB - OBJECTIVE: To find out whether changes in the daily prothrombin time are of prognostic importance in patients with paracetamol induced fulminant hepatic failure. DESIGN: Retrospective study. SETTING: The Liver Unit, King's College Hospital, London. PATIENTS: 150 Consecutive patients with paracetamol induced fulminant hepatic failure admitted between October 1986 and February 1989. MAIN OUTCOME MEASURE: Death. RESULTS: Of the 150 patients, 72 (48%) died. In all, 34 of the 37 (92%) patients with a peak prothrombin time of greater than or equal to 180 seconds died as did 20 of the 41 (49%) with a time of 130-179 seconds, nine of the 25 (36%) with a time of 90-129 seconds, and nine of the 47 (19%) with a time of less than 90 seconds. Of the 42 patients with a continuing rise in prothrombin time between days 3 and 4 after overdose, 39 died (93%) compared with 21 of the 96 (22%) in whom the prothrombin time fell. CONCLUSIONS: These data indicate that a continued increase in prothrombin time on day 4 after overdose and a peak prothrombin time of greater than or equal to 180 seconds identify at an early stage those patients with a less than 8% chance of survival. Liver transplantation should be considered in patients meeting either of these criteria. PMID- 2249027 TI - Recurrent rupture of intracranial aneurysms in autosomal dominant polycystic kidney disease. PMID- 2249028 TI - Prevalence of Dupuytren's contracture in patients infected with HIV. PMID- 2249029 TI - Analysing ordered categorical data from two independent samples. PMID- 2249030 TI - ABC of major trauma. Trauma in pregnancy. PMID- 2249031 TI - Carbon monoxide poisoning in the home: recognition and treatment. PMID- 2249032 TI - Smoke detectors save lives. PMID- 2249033 TI - Follow up of women with dyskaryotic cervical smears. PMID- 2249034 TI - Whiplash injury. PMID- 2249035 TI - General practitioner maternity units. PMID- 2249036 TI - Early detection of gastric cancer. PMID- 2249037 TI - HIV infection and foreign travel. PMID- 2249038 TI - Low level exposure to lead. PMID- 2249039 TI - The epidemiology of malpractice. PMID- 2249040 TI - Tanning with ultraviolet A sunbeds. PMID- 2249041 TI - Sodium-lithium countertransport activity in red blood cells. PMID- 2249042 TI - Colitis associated with ibuprofen. PMID- 2249043 TI - Clinical recognition of early invasive malignant melanoma. PMID- 2249044 TI - Do streptococci cause toxic shock? PMID- 2249045 TI - Sexual expression in paraplegia. PMID- 2249046 TI - Juniors' hours: measuring the strength of feeling. PMID- 2249047 TI - What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust. AB - OBJECTIVE: To investigate the role of occupational and domestic exposure to dust in the aetiology of cryptogenic fibrosing alveolitis. DESIGN: Matched case control study. SUBJECTS: 40 Patients with cryptogenic fibrosing alveolitis and 106 community controls matched for age and sex who responded to a questionnaire. MAIN OUTCOME MEASURE: Responses to self administered questionnaire asking about lifetime exposure to dust, animals, and smoke at home and at work. RESULTS: The patients with cryptogenic fibrosing alveolitis were more likely to report occupational exposure to metal dust (matched odds ratio 10.97 (95% confidence interval 2.30 to 52.4), p less than 0.001) or wood dust (2.94 (0.87 to 9.90), p = 0.08), to have worked with cattle (10.89 (1.24 to 96.0), p = 0.01), and to have lived in a house heated by a wood fire (12.55 (1.04 to 114), p = 0.009). A history of smoking and social class based on occupation were not significantly related to disease state. CONCLUSION: Environmental exposure to dust may be an important factor in the aetiology of cryptogenic fibrosing alveolitis. PMID- 2249048 TI - Rising mortality from cryptogenic fibrosing alveolitis. AB - OBJECTIVE: To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN: A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979 87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES: Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS: The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS: The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology. PMID- 2249049 TI - Home treatment for acute psychiatric illness. AB - OBJECTIVE: To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. DESIGN: All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. SETTING: Electoral ward of Sparkbrook, Birmingham. SUBJECTS: 99 Patients aged 16-65 with severe acute psychiatric illness. RESULTS: 65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. CONCLUSIONS: Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service. PMID- 2249050 TI - Accuracy of clinical diagnosis of Alzheimer's disease. PMID- 2249051 TI - Life threatening injuries to the chest caused by plastic bullets. PMID- 2249052 TI - How much personal care in four group practices? AB - OBJECTIVE: To establish the degree of continuity of care in general practice. DESIGN: Retrospective study of the records of all eligible patients attending the surgery at randomly selected sessions. SETTING: Four large group practices in the Southampton Health District, one of which operated a strict system of personal lists. PATIENTS: 776 Patients who had been registered for at least two years and had consulted at least 12 times over six years or less. MAIN OUTCOME MEASURES: Continuity score for each patient calculated from the number of consultations (out of the past 12) with his or her usual doctor. Number of the times the patients had consulted the doctor with whom they were registered. RESULTS: In the practice with personal lists a mean of 10 of the 12 consultations had been with the same doctor (83% of consultations), but in the three practices with combined lists the means were 5.9 (49%), 6.2 (52%), and 6.9 (58%). Continuity was associated with increased age and with the recording of a major problem. In the practices with combined lists 63 of 72 children consulted at least five different doctors. Only 140 of 489 patients currently in the practice who were identified as being registered with a doctor had most usually consulted that doctor in the practices with combined lists. CONCLUSIONS: Personal continuity of care may be fairly low in group practice, especially for younger and healthier patients registered at practices with combined lists. These findings support the Department of Health's recent decision to make "target payments" (for cervical smears and childhood immunisations) to groups rather than to individual principals but pose a question for the future of individual clinical responsibility. PMID- 2249053 TI - The population mean predicts the number of deviant individuals. AB - OBJECTIVE: To examine the relation between the prevalence of deviation and the mean for the whole population in characteristics such as blood pressure and consumption of alcohol. DESIGN: Re-examination of standardised data from the Intersalt study, an international, multicentre study on the determinants of blood pressure. SETTING AND SUBJECTS: Samples of adults representing 52 populations in 32 countries. MAIN OUTCOME MEASURES: The relations, expressed as correlation coefficients, between the mean population values for blood pressure, body mass index, alcohol consumption, and sodium intake and the prevalence of, respectively, hypertension (greater than or equal to 140 mm Hg), obesity (body mass index greater than or equal to 30 kg/m2), high alcohol intake (greater than or equal to 300 ml/week), and high sodium intake (greater than or equal to 250 mmol/day). RESULTS: There were close and independent associations between the population mean and the prevalence of deviance for each of the variables examined: correlation coefficients were 0.85 for blood pressure, 0.94 for body mass index, 0.97 for alcohol intake, and 0.78 for sodium intake. CONCLUSIONS: These findings imply that distributions of health related characteristics move up and down as a whole: the frequency of "cases" can be understood only in the context of a population's characteristics. The population thus carries a collective responsibility for its own health and well being, including that of its deviants. PMID- 2249054 TI - Visit a health centre in a developing country. PMID- 2249055 TI - Kwashiorkor. PMID- 2249056 TI - Crutches. PMID- 2249057 TI - ABC of major trauma. Blast and gunshot injuries. PMID- 2249058 TI - Bacteria and arthritis. PMID- 2249059 TI - Guidelines for management of asthma. PMID- 2249060 TI - Invasive aspergillosis in immunosuppressed patients. PMID- 2249061 TI - Osteoporosis after 60. PMID- 2249062 TI - Acid suppression. PMID- 2249063 TI - Neonatal intubation with the Cole tube. PMID- 2249064 TI - Myocardial infarction associated with dextrofenfluramine. PMID- 2249065 TI - Importance of ovulation in ovarian cancer. PMID- 2249066 TI - Retreat from general practice. PMID- 2249067 TI - Australia boosts AIDS research. PMID- 2249068 TI - Opiate addiction in adult offspring through possible imprinting after obstetric treatment. AB - OBJECTIVE: To test the hypothesis that opiate addiction in adults might stem partly from an imprinting process during birth when certain drugs are given to the mother. DESIGN: Retrospective study by logistic regression of opiate addicts with siblings as controls. SETTING: Stockholm, Sweden. SUBJECTS: 200 Opiate addicts born in Stockholm during 1945-66, comprising 41 identified during interviews of probands for an earlier study; 75 patients whose death from opiate addiction had been confirmed during 1978-88; and 84 accepted for the methadone programme. 262 Siblings (controls) born in Stockholm during the same period, 24 of whom were excluded for drug addiction or being brought up outside the family. Birth records were unavailable for eight, leaving 230 siblings and 139 corresponding probands. MAIN OUTCOME MEASURES: Administration of opiates, barbiturates, and nitrous oxide (for greater than 1 h) to mothers of all subjects during labour within 10 hours before birth as a risk factor for adult opiate addiction. RESULTS: In subjects who had subsequently become addicts a significant proportion of mothers had received opiates or barbiturates, or both, compared with unmatched siblings (25% v 16%, chi 2 = 5.83, df = 1, p = 0.02), and these mothers had received nitrous oxide for longer and more often. After controlling for hospital of birth, order of birth, duration of labour, presentation other than vertex, surgical intervention, asphyxia, meconium stained amniotic fluid, and birth weight the relative risk for offspring subsequently becoming an adult opiate addict increased with the number of administrations of any of the three drugs. When the addicts were matched with their own siblings the estimated relative risk was 4.7 (95% confidence interval 1.8 to 12.4, p for trend = 0.002) for three administrations compared with when no drug was given. CONCLUSIONS: The results are compatible with the imprinting hypothesis. Therefore, for obstetric pain relief methods are preferable that do not permit substantial passage of drugs through the placenta. PMID- 2249069 TI - Can prepregnancy care of diabetic women reduce the risk of abnormal babies? AB - OBJECTIVE: To see whether a prepregnancy clinic for diabetic women can achieve tight glycaemic control in early pregnancy and so reduce the high incidence of major congenital malformation that occurs in the infants of these women. DESIGN: An analysis of diabetic control in early pregnancy including a record of severe hypoglycaemic episodes in relation to the occurrence of major congenital malformation among the infants. SETTING: A diabetic clinic and a combined diabetic and antenatal clinic of a teaching hospital. PATIENTS: 143 Insulin dependent women attending a prepregnancy clinic and 96 insulin dependent women managed over the same period who had not received specific prepregnancy care. MAIN OUTCOME MEASURE: The incidence of major congenital malformation. RESULTS: Compared with the women who were not given specific prepregnancy care the group who attended the prepregnancy clinic had a lower haemoglobin AI concentration in the first trimester (8.4% v 10.5%), a higher incidence of hypoglycaemia in early pregnancy (38/143 women v 8/96), and fewer infants with congenital abnormalities (2/143 v 10/96; relative risk among women not given specific prepregnancy care 7.4 (95% confidence interval 1.7 to 33.2]. CONCLUSION: Tight control of the maternal blood glucose concentration in the early weeks of pregnancy can be achieved by the prepregnancy clinic approach and is associated with a highly significant reduction in the risk of serious congenital abnormalities in the offspring. Hypoglycaemic episodes do not seem to lead to fetal malformation even when they occur during the period of organogenesis. PMID- 2249070 TI - Ultrasonography compared with intravenous urography in the investigation of adults with haematuria. AB - OBJECTIVE: To compare ultrasonography with intravenous urography in the investigation of adults with haematuria. DESIGN: Prospective study entailing the examination of all patients with both investigations concurrently. The investigations were performed independently on routine lists by different duty radiologists. Each was aware of the details of the request form but not of the findings of the other investigation. SETTING: Radiology department of a teaching hospital. PATIENTS: 155 Consecutive adult patients (aged 18-93) referred from general practitioners and hospital outpatient clinics with a history of haematuria. FOLLOW UP: When results of both examinations proved normal no clinical or radiological follow up was sought. All abnormal findings of either investigation were correlated with results of subsequent imaging studies or operative findings. RESULTS: 81 Patients (52%) had normal findings on urography and ultrasonography. Overall, the findings of ultrasonography concurred with those of urography in 144 cases (93%). Among the discrepant findings of the two investigations ultrasonography missed two ureteric calculi; one was in a non dilated ureter, and in the other case ultrasonography detected the secondary ureteric dilatation. Ultrasound examination alone detected four bladder tumours not visible on urography with sizes ranging from 5 to 21 mm, representing one fifth of the 20 cystoscopically proved bladder tumours detected in the series. Ultrasonography detected all the 22 neoplastic lesions discovered in the study (20 bladder, two renal). Ultrasonography clarified the nature of renal masses evident in three urograms (simple cysts). CONCLUSIONS: Ultrasonography is a safe and accurate method of investigating the urinary tract in adults with haematuria. When combined with a single plain abdominal radiograph it proved to be superior to urography as the primary imaging study in this series. Ultrasonography should certainly be preferred to urography if cystoscopy is not planned. No urothelial tumours of the upper urinary tract were found in the series, reflecting their rarity. For those patients in whom ultrasonography and plain radiography have shown no abnormality and in whom cystoscopic appearances are normal urography would be advisable to exclude urothelial tumours of the upper urinary tract. PMID- 2249071 TI - Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation. AB - OBJECTIVE: To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation's studies of Hodgkin's disease since 1970. PATIENTS: 2676 Patients entered into Hodgkin's disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN: Retrospective analysis of multicentre trial data by case-control and life table methods. RESULTS: 17 Cases of secondary leukaemia were recorded in this group of 2676 patients, giving an overall risk at 15 years of 1.7%. The risks of leukaemia after chemotherapy alone and chemotherapy with radiotherapy were not significantly different. The risk of leukaemia increased sharply with the amount of treatment given as measured by the number of attempts at treatment. The 15 year risks of leukaemia were 0.2%, 2.3%, and 8.1% for patients receiving one, two, or three or more attempts at treatment. The highest risk, 22.8% at 15 years, was observed in patients treated with lomustine (CCNU), and a case-control study suggested that this was an independent risk factor. The risk of secondary leukaemia was largely related to the overall quantity of treatment, although exposure to lomustine seemed to be an important risk factor. Treatment with both drugs and radiation was not more leukaemogenic than treatment with drugs alone. The greatest risk of secondary leukaemia was seen in multiply treated patients who were unlikely to be cured of Hodgkin's disease. CONCLUSIONS: Avoidance of secondary leukaemia should be a minor factor in the choice of treatment for Hodgkin's disease. PMID- 2249072 TI - Ischaemic colitis as a complication of colonoscopy. PMID- 2249073 TI - Development of renal scars in children: missed opportunities in management. South Bedfordshire Practitioners' Group. AB - OBJECTIVE: To assess the antecedent medical care of children with renal scars. DESIGN: Retrospective study of both general practice and hospital records. SETTING: 12 Group practices in south Bedfordshire and the radiology and paediatric outpatient departments of a district general hospital. SUBJECTS: 23 Children with renal scars (six boys, 17 girls) from the 12 group practices, identified from outpatient, radiology, and general practice records. MAIN OUTCOME MEASURES: Number of children in whom a diagnosis of urinary tract infection had been made without prior examination of a mid-stream specimen of urine; number of children who had had a confirmed urinary tract infection that had not been investigated further; number who had experienced delays in investigation or referral; and number who had received inadequate follow up. RESULTS: In all, 11 of the children had received suboptimal medical care, but the management of the other 12 could not have been better. The most common error was failure to investigate possible urinary tract infections, but follow up of confirmed infections was also inadequate. These problems occurred in hospital as well as in general practice. CONCLUSION: Opportunities for intervention had been missed in nearly half of this sample of children with renal scars. PMID- 2249074 TI - Crisis in our schools: survey of sanitation facilities in schools in Bloomsbury health district. AB - OBJECTIVE: To survey sanitation facilities in schools in Bloomsbury health district. DESIGN: Postal questionnaire. SETTING: Inner London health district. PARTICIPANTS: School nurses. RESULTS: 16 of 17 school nurses responded (37 of 41 schools). Fifteen schools did not have the minimum number of toilets and hand basins established in the Education (School Premises) Regulations 1981. In two schools toilets were kept locked for most of the day. In 10 schools toilet paper was not always available, and three of five secondary schools did not have disposal units for sanitary towels in the girls' toilet areas. In 18 of the schools the toilets were not kept adequately clean. CONCLUSIONS: These conditions raise serious questions about environmental health, with the potential for the spread of infectious diseases, and undermine attempts to teach children basic hygiene. Health professionals have an important role in assessing health and safety standards in schools and ensuring that necessary improvements are made. PMID- 2249076 TI - NHS trusts. PMID- 2249077 TI - Disability among people with mental handicaps. PMID- 2249075 TI - Adult respiratory distress syndrome. Advances in diagnosis and ventilatory management. PMID- 2249078 TI - Shoulder pain in the elderly. PMID- 2249079 TI - Prediction of hip fracture in elderly women. PMID- 2249080 TI - Unawareness of hypoglycaemia. PMID- 2249081 TI - Consultation rates among middle aged men. PMID- 2249082 TI - New agenda for general practice computing. PMID- 2249083 TI - Atenolol in essential hypertension during pregnancy. PMID- 2249084 TI - Obstetrics and the general practitioner. PMID- 2249085 TI - [Academic eulogy of Professor Yves Ruckebusch, foreign correspondent]. PMID- 2249086 TI - [The molecular basis of the virulence of Yersinia]. AB - Pathogenic bacteria of the genus Yersinia (Y. enterocolitica, Y. pseudotuberculosis and Y. pestis) are pathogens of the invasive type. Although they provoke diseases as different as plague and enterocolitis, the molecular bases of their virulence appear to be surprisingly similar: a 70 kb plasmid confers a degree of resistance to the primary immune response and the presence or absence of chromosome encoded functions modulates virulence. The knowledge of the virulence functions that now emerges suggests the conversion of Y. enterocolitica as a life carrier. PMID- 2249087 TI - [Hibernal respiratory disorders]. AB - A long term serological surveillance of the acute respiratory illnesses was conducted, looking for infections by adenoviruses, influenza A.B.C. parainfluenza 1,2,3 and respiratory syncytial viruses as well as Mycoplasma pneumoniae, Coxiella burneti and Chlamydia psittaci. The analysis of the results accumulated for the past 20 years was carried out. Influenza C. Coxiella burneti and Chlamydia psittaci infections were rare and could not account for any epidemic prevalence. The other agents produced mostly winter infections, but their contribution to the annual peak varied from year to year. One or several infections were associated with 21% of our total number of acute respiratory illnesses. Beside their close association with winter disease, the respiratory agents could be found all over the year, both amongst patients with or without respiratory tract involvement. To identify the above mentioned viruses we have been using monoclonal antibodies for 30 months including three epidemic seasons. From december 1987 on, we examined nearly 600 cell specimens collected by pharyngeal washing amongst young children admitted to local hospitals for respiratory tract involvement. The results were in agreement with those given by the serological surveillance. We still lack convenient methods to identify the agents which could account for most of the common acute respiratory diseases. PMID- 2249088 TI - [Aging of nerve tissue]. AB - In the peripheral nervous system, the various alterations, which are the manifestations of the ageing deleterious process, appear according to a precise chronology and, obviously, degradation does not depend on the cell body microenvironment. On the other hand, alterations in the fibres environment could enhance the deleterious process. Similarly, the quality of the environment of the organism itself could act to modulate the spreading of the alterations. It should be strenghtened that the neuron never losses its capacities to react against aggressions, for instance by forming new fibres. In the central nervous system, a toxic activity develops with advancing age, which could be responsible for the neuronal depopulation. Schematically, the neuronal capacities during ageing appear more dependent on the relationships between the neurons and their target organs than on the neurons themselves. PMID- 2249089 TI - Fast neutron therapy damned. PMID- 2249090 TI - Neutron therapy defended. PMID- 2249091 TI - Problems of recruiting ovum donors. PMID- 2249092 TI - New antiepileptic drugs. PMID- 2249093 TI - Multidisciplinary teams create problems for consultants. PMID- 2249094 TI - JPAC quotas unrealistic without increased funding. PMID- 2249095 TI - The moral consensus on euthanasia. PMID- 2249096 TI - Barts Careflight: a truly nationwide service. PMID- 2249097 TI - Haemospermia: a complication of thrombolytic therapy. PMID- 2249098 TI - Heparin-induced thrombocytopenia. PMID- 2249099 TI - Drugs and the bone marrow. AB - Some drugs have a predictable suppressive effect upon the bone marrow and are used in the treatment of malignant disease. Others are unpredictable and may cause unanticipated side effects to bone marrow during the treatment of non malignant pathologies. In this article, bone marrow maturation is discussed and both the defined and potential effects of drugs upon the bone marrow are considered. PMID- 2249100 TI - Mechanisms and clinical significance of resistance to new beta-lactam antibiotics. AB - The newer beta-lactam antibiotics, including various ureidopenicillins, second- and third-generation cephalosporins, carbapenems and monobactams, are active against many bacteria that are resistant to older penicillins, such as ampicillin and ticarcillin. Nonetheless, resistance to the newer agents can arise, and in this article the mechanisms whereby it does so are reviewed and their clinical significance is discussed. PMID- 2249101 TI - Zopiclone. PMID- 2249102 TI - Management of congenital tracheal stenosis in infants. AB - Until recently congenital tracheal stenosis presenting in infants was considered to be almost invariably lethal. With improved diagnostic, anaesthetic and surgical techniques virtually all cases are potentially curable. Prompt recognition and early surgical intervention, combined with skilled perioperative management, will result in a more favourable outcome. PMID- 2249103 TI - Disorders of ocular motility. AB - Disorders of ocular motility usually present with double vision which may be accompanied by ptosis and pupillary changes. The differential diagnosis comprises supranuclear, nuclear and infranuclear palsies and diseases of the myoneural junction. Accurate assessment is important, since the aetiological possibilities include neurosurgical emergencies such as intracranial aneurysm and systemic problems such as diabetes mellitus. PMID- 2249104 TI - Exploratory burr holes. AB - The ability to enter the cranial cavity rapidly and effectively is a mandatory skill for those managing the head-injured patient. It may be increasingly required now that earlier computed tomography diagnosis of non-traumatic intracranial lesions is made in centres without the immediate assistance of a neurosurgeon. PMID- 2249105 TI - Renal transplantation in children. AB - Transplantation with a renal allograft is the treatment of choice for the child with end-stage renal failure. Over the past 20 years rapid advances have made it possible to transplant a kidney of adult proportions into a child aged 1 year or less. Actuarial graft survival at 5 years for first cadaveric kidneys is more than 60% in children aged less than 5 years. Long-term studies have demonstrated an improvement in linear growth and preservation of glomerular filtration rate. PMID- 2249106 TI - Molecular medicine. AB - The enormous advances in the biological sciences are making a dramatic impact upon clinical medicine. The emerging specialty of molecular medicine applies these theoretical and technological advances to understanding the causes, expression and rational treatment of human disease. PMID- 2249107 TI - The premenstrual syndrome. AB - The recognition of the relationship between premenstrual syndrome and cyclical ovarian activity has enabled the rationalization of treatment. Placebo-controlled studies have established the efficacy of treatments that alter ovarian function, therefore it should no longer be necessary to rely on the placebo effect of unproven treatments such as progesterone. PMID- 2249108 TI - Asystole following butane gas inhalation. PMID- 2249110 TI - Family screening for duplex kidneys. AB - Family screening was offered to the relatives of 57 patients with duplex renal systems and this resulted in the detection of another 37 cases. A further 5 first degree relatives had abnormal intravenous urography, so that 25% of the screened relatives had significant renal abnormalities. It is suggested that there may be a place for screening the whole family if renal tract duplex is detected. PMID- 2249109 TI - Prostatectomy--an open or closed case. PMID- 2249111 TI - Dilatation in the duplex kidney: 3 unusual cases. AB - Dilatation in the upper limb of a duplex ureter is usually secondary to obstruction and may be associated with a ureterocele. By contrast, vesicoureteric reflux is the usual cause of a dilated lower moiety ureter. We report 3 cases in which unusual or complex causes of dilatation of 1 limb of a duplex ureter were demonstrated. PMID- 2249112 TI - Crystalluria, medullary matrix crystal deposits and bladder calculi associated with an acutely induced renal papillary necrosis. AB - A single (100 mg/kg) intraperitoneal dose of 2-bromoethanamine hydrobromide induced renal papillary necrosis (RPN) acutely in rodents and caused a transient crystalluria between 4 and 8 h after dosing. These crystals comprised struvite or magnesium ammonium phosphate (MAP) as assessed by shape, solubility, infra-red spectrum and X-ray microprobe analysis. Acid-soluble, bi-refringent crystals were also present within the renal medullary matrix during the same time period as the crystalluria. The presence of the MAP was associated with loss of the anionic renal medullary mucopolysaccharides staining. A total of 5/64 rats with a 2 bromoethanamine-induced renal papillary necrosis and monitored for up to 160 days had bladder calculi that were predominantly MAP. These data suggest that medullary mucopolysaccharide matrix disruption associated with RPN leads to a release of previously bound cations, super-saturation and the nucleation of crystalline MAP. These processes could also be implicated in the formation of MAP bladder calculi. PMID- 2249113 TI - The encased ureter: bullet and bodkin pattern, a reliable radiographic sign. AB - Among the causes of constricted ureter is benign or malignant encasement. The diagnosis of ureteric encasement is frequently overlooked, even by well informed clinicians and radiologists. The most common benign cause is retroperitoneal fibrosis and the most frequent malignant causes are extension from an adjacent primary tumour, true metastases to the ureter and lymphoma. Lack of recognition of the process may lead to mistaken diagnosis of an inflammatory stricture or infiltrating transitional cell tumour, with resultant inappropriate management. A sign which appears to be almost specific for encasement, the bullet and bodkin configuration, is described here. Newer imaging modalities such as computed tomography and ultrasound, while helpful, are probably less sensitive and less specific than the retrograde ureterogram because a detectable mass is not always present. PMID- 2249114 TI - Bladder function in the mentally retarded. AB - A group of 21 mentally retarded patients with severe, long-standing urinary symptoms underwent urodynamical investigation. The most common abnormalities were detrusor areflexia and detrusor hyper-reflexia. Of 11 patients treated surgically, 10 derived marked benefit. Drugs were successful in reducing micturition problems in 3/6 patients. Severely retarded patients with spastic quadriplegia are difficult to investigate and if this is associated with detrusor hyper-reflexia it is impossible to treat them in any way. Severely retarded patients with detrusor areflexia and infrequent voiding can benefit from bladder outlet surgery. Patients with moderate (especially mild) retardation can be investigated and treated in the same way as non-retarded people. PMID- 2249115 TI - Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability. AB - Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy. PMID- 2249116 TI - Response to treatment of detrusor instability in relation to psychoneurotic status. AB - A total of 53 females who entered a double-blind crossover trial of oxybutynin and placebo for idiopathic detrusor instability were questioned about life events and associated medical disorders and were given a psychometric test. Their response to treatment was studied in relation to these factors. It was found that 11% of patients had nocturnal enuresis beyond age 8 and 25% had irritable bowel syndrome: their response to treatment was generally poor. Life events were not consistently related to treatment response. The mean psychoneurotic score of "poor responders" (43.7) was similar to that of female psychoneurotic out patients (47.7), although one-third of poor responders were normal. Patients who responded well to simple anticholinergic treatment had a mean score (30.7), which was similar to that of normal urban females (33.5). Most good responders and one third of poor responders showed little evidence of psychoneuroticism: a further search for neurophysiological abnormality in idiopathic detrusor instability is needed. PMID- 2249117 TI - Double-blind, placebo-controlled, cross-over study of flavoxate in the treatment of idiopathic detrusor instability. AB - Detrusor instability occurs in approximately 10% of the adult population, producing troublesome symptoms. The pharmacotherapy currently available is usually only partially effective and cannot be adequately evaluated except under "blind" conditions because of the significant component attributable to placebo effects. The results of the present study revealed no advantage resulting from treatment with flavoxate, as assessed both subjectively and objectively. We suggest that this therapy does not appear to be beneficial in the medical management of detrusor instability. PMID- 2249118 TI - The perineal artificial sphincter for acquired incontinence--a cut and dried solution? AB - Sixteen males with stress incontinence due to sphincter damage were investigated with videourodynamic studies after implantation of a perineal artificial urinary sphincter. Twelve patients were rendered dry; 4 remained incontinent, all of whom were shown by cystometry to have incontinence from detrusor instability. Of these, 2 also had stress incontinence proven by videourography. Detrusor instability was present in 9 patients before implantation; the instability worsened considerably in 2 patients and new instability was shown in another 2 patients. The limitations of the artificial urinary sphincter and the implications of detrusor instability in patients with an artificial sphincter are discussed. The artificial urinary sphincter is an extremely successful device for the treatment of acquired stress incontinence. PMID- 2249119 TI - Foley catheter balloon puncture and the risk of free fragment formation. AB - The incidence of free fragment formation following balloon puncture or spontaneous bursting was examined in 294 Foley catheters immersed for 48 h in urine. The catheters were divided into 3 groups: 100 were inflated to the manufacturer's recommended volume, 100 to twice the volume and 94 to 3 times the recommended volume. The catheter balloons were punctured by pricking with a hypodermic needle. The overall incidence of free fragment formation was 27.3%. For both types of catheter examined, increasing balloon volume was not associated with an increased risk of free fragment formation following puncture. However, increasing volume was associated with increased free fragment formation when the balloon burst spontaneously. In view of the high risk of free fragment formation, cystoscopy should be performed in all cases of spontaneous catheter balloon rupture or after percutaneous balloon puncture. PMID- 2249120 TI - Urinary infection following out-patient flexible cystoscopy. AB - Of 161 flexible cystoscopies performed in an out-patient endoscopy suite, the incidence of urinary tract infection was 7.5%. Infection rates were higher in patients with a history of previous urinary tract infection or where an additional procedure was also performed. No difference was noted between the infection rates in men and women. PMID- 2249121 TI - Antibiotic compared with antiseptic prophylaxis for prostatic surgery. AB - Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association between the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of post-operative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per operative urinary infection or catheterisation. PMID- 2249122 TI - Serum levels of sex hormone binding globulin and oestradiol in patients with testicular cancer. AB - Serum testosterone (T), oestradiol (E-2) and sex hormone binding globulin (SHBG) were measured in 84 orchiectomised testicular cancer patients before further treatment and 4 to 6 and 12 to 15 months after therapy. Patients were divided into 3 groups according to treatment: Group 1: cisplatin-based chemotherapy (27 patients); Group 2: abdominal radiotherapy (32 patients); Group 3: no antiproliferative treatment (chemotherapy/radiotherapy) (25 patients). Between 4 and 6 months after antiproliferative treatment, particularly after chemotherapy, a reversible significant increase in E-2 and SHBG was observed. Patients without antiproliferative treatment showed no significant changes in their comparable hormone levels; 15% of all normal T values were associated with elevated levels of SHBG and E-2. Although the aetiology of these hormonal changes remains unknown, they may be related to the clinical symptoms of hypogonadism displayed by 10 to 30% of patients undergoing treatment for testicular cancer. PMID- 2249123 TI - Surgical approach to the retrocrural lymph nodes. AB - Removal of retrocrural lymph nodes requires an approach other than the infradiaphragmatic retroperitoneal access generally used in the surgical management of testicular tumours. The transperitoneal route given access, at best, to the origin of the superior mesenteric artery, but advanced testicular tumours occasionally require retrocrural node dissection. We describe a useful surgical approach to these nodes and the underlying anatomy. PMID- 2249124 TI - Blunt renal trauma in childhood. Features indicating severe injury. AB - The clinical presentation of children with blunt renal trauma may differ from that of adults. The clinical features at presentation of 50 consecutive children (20 severe injuries, no pedicle injuries) admitted over a period of almost 8 years were reviewed to determine if there were clinical clues to major renal trauma in childhood. Gross haematuria and low haematocrit were the most helpful factors at the time of presentation and correlated well with severe renal injury. Hypotension was seen in 4 patients and only 1 had severe renal trauma. Suspicion of a major renal injury should be high when there is gross haematuria or a low haematocrit. In this study only 1 of 20 patients with major renal injury demonstrated clinical signs of shock. Unlike adults, hypotension does not appear to be a reliable indicator of the severity of renal injury in children and diagnostic evaluation should not be reserved only for those in shock. PMID- 2249125 TI - Treatment of infants with neurogenic bladder dysfunction using anticholinergic drugs and intermittent catheterisation. AB - The use of anticholinergic drugs in infants with neurogenic dysfunction has not been well documented. In this study, 35 neonates at risk of upper urinary tract damage from neurogenic dysfunction were treated from infancy with anticholinergics, in combination with clean intermittent catheterisation. None of the patients showed upper urinary tract deterioration with follow-up ranging from 6 to 72 months, although 2 required vesicostomy--1 due to difficulty with catheterisation and 1 due to possible anticholinergic side effects. Only 2 (6%) have had clinical pyelonephritis. Twenty-five (76%) are virtually dry between catheterisation. We conclude that anticholinergics are safe and effective, even in the neonatal period, when used in combination with clean intermittent catheterisation for the treatment of neonates with neurogenic bladder dysfunction. PMID- 2249126 TI - Treatment with desmopressin in severe nocturnal enuresis in childhood. AB - A series of 22 patients with severe nocturnal enuresis were treated with desmopressin in a randomised double-blind cross-over study. Treatment with 20 and 40 micrograms was highly effective compared with placebo. No difference in dry nights was found between the 2 dosages. Desmopressin proved to be a safe and effective treatment. PMID- 2249127 TI - Vasa aplasia and cystic fibrosis. AB - Bilateral vasa aplasia is considered an invariable finding in cystic fibrosis, but such patients are rarely seen in male infertility clinics. The improved survival beyond 20 years of age is likely to change this. In a clinical study of a group of male cystics the vasa were absent in 8 of 11 boys and epididymal abnormalities were palpable in the majority. The main cause of infertility appears to be mechanical obstruction. Whether the absence is due to a primary failure of mesonephric duct development or secondary to luminal obstruction and subsequent atrophy is not known. PMID- 2249128 TI - The effect of post-pubertal varicocele on testicular volume. AB - Paediatric varicocele is a well known entity but its effect on adult infertility has not been adequately clarified. Since measurement of testicular volume is currently the best method of estimating the male reproductive potential, 945 boys aged between 13 and 18 years were examined with regard to testicular volume and the incidence of varicocele. The average volumes for right and left testes were 15.087 +/- 0.237 and 14.514 +/- 0.347 ml respectively, and the incidence of varicocele was 16.7%. The incidence increased from 14.5 to 21.7% as the ages increased from 14 to 18. The differences in volume of the 2 testes in boys with varicocele were statistically significant when compared with the normal group, but this significance failed to become more pronounced when the slight varicocele group (grade I) was included with the normal group and compared with the severe varicocele group (grades II and III). There may be no significant differences between the volumes of the 2 testes in boys with varicocele when careful measurement and strict statistical analyses are applied. However, some boys in the varicocele group were found to have testicular volumes below the confidence interval (mean - SE) or under 1 SD, and the 2 testicular volumes differed in certain age groups. This group requires further follow-up. The results of this study have added further contradictory findings to the issue of paediatric varicocele in terms of testicular atrophy, estimation of potential fertility and the indications for immediate surgery. There is a need for further prospective controlled trials. PMID- 2249129 TI - Acute urinary retention: a unique complication of primary varicella infection of childhood. PMID- 2249130 TI - Hydrops tubae profluens--not a genitourinary fistula but a diagnosis to be missed. PMID- 2249131 TI - Actinomycosis causing ureteric obstruction. PMID- 2249132 TI - The AS 800 urinary sphincter in renal transplantation. PMID- 2249133 TI - Urethralisation of the female phallus with absent urogenital sinus. PMID- 2249134 TI - Primary osteosarcoma of penis. PMID- 2249135 TI - Suprapubic catheterisation using a guidewire and dilators. PMID- 2249136 TI - Introduction of a Foley catheter by puncture suprapubic cystostomy. PMID- 2249137 TI - Re: Giant posterior urethral calculus. A. Bolukbasi and B. Gumus. Br. J. Urol., 65, 301-302, 1990. PMID- 2249138 TI - Re: Relationship between intermittent hydronephrosis and megacalicosis.P.H. O'Reilly. Br. J. Urol., 64, 125-129, 1989. PMID- 2249139 TI - [Assessment of the content of small peptides in enzymatic proteolysates using a cuprimetric method: value in nutritional medicine]. AB - The nutritional interest of dipeptides and tripeptides is more and more recognized nowadays. Directly absorbed by enterocyte, they enable to improve the transfer of amino acids not easily absorbable. The quality of proteins hydrolysates mainly depends on the importance of their concentration. But official methods of analysis of protein hydrolysates (total nitrogen, alpha amino nitrogen) are inept to estimate their concentrations. It is possible to realize this estimation by grounding on reactivity with Cu II. Indeed like free amino acids they can give complexes with this ion. The proposed cuprimetric method loads to a more sensible estimation, and especially it's possible to differentiate homogeneous hydrolysates from mixtures which have been added with amino acids. Theirs it enables the nutritional physician to have a better knowledge of the biodisponibility of this preparation. PMID- 2249140 TI - [Eulogy for Alfred-Gilbert Dreyfus (1902-1989)]. PMID- 2249141 TI - [Value of a study of contrast sensitivity in the evaluation of visual function: applications to pathology and visual selection]. AB - Spatial contrast sensitivity function appears to give the most general description available for the basic aspect of spatial visual performance. Classical measurement of visual acuity is unable to give us a fine appreciation of visual function. Visual acuity is only one aspect of the complex process of sight. We have tested contrast sensitivity to detect silent lesions of the visual pathway. In multiple sclerosis we have demonstrated a bilateral involvement in almost all cases. In primary open angle glaucoma contrast sensitivity is affected before perimetry data are able to show any defect. We have the same results in early stages of diabetic retinopathy. Contrast sensitivity testing shows great promise for detection of eye defect in drivers and industry workmen. PMID- 2249142 TI - [Medicine and archaeology: comparison of methods]. AB - Medicine and archaeology are human sciences: their diagnostic claim consists of establishing the link between the singular case and the general model. Comparing and contrasting the two processes is not limited to a game of "similarities differences". It makes possible a finer analysis of different methods of data collection, either with or without the help of instruments, and a comparison of different ways of handling and classifying symptoms observed and documentary evidence gathered. It shows that archaeology, in contrast to medicine (with physiology and health), has as a discipline, no real precisely defined reference. It is suggested that it is in the interest of medicine and archaeology to compare their own working methods...and their imperfections. PMID- 2249143 TI - [New immunopathogenic aspects of IgA nephropathy]. AB - IgA nephropathy (Berger's disease) has become recognized worldwide as one of the most common of the primary glomerulonephritis. The mesangial granular deposits suggested an immune complex disease. The available data evidence that the IgA circulating immune complexes in these patients are heterogeneous. Recent analysis, performed after dissociating the complexes, found both IgA1 and IgG. In fact, high serum levels of IgA rheumatoid factor and shared antibody idiotypes were found in a large proportion of those patients. A close relationship was noted between the presence of cross-reactive idiotypes on mesangial immunoglobulins and the existence of increase levels of serum idiotypes and many patients have increased rates of IgA synthesis either spontaneously or after stimulation of the peripheral blood mononuclear cells by various mitogens. A lot of abnormalities on B and T lymphocytes, related with the IgA immune regulation, have been described. Most of deposited IgA in the mesangium is polymeric and belongs to the IgA1 class. Patients with IgA nephropathy have very often antibodies against exogenous and endogenous antigens. Among the most frequently found are the antibodies against dietary, viral and bacterial antigens as well as against the Fc and Fab portions of immunoglobulins, nuclear and glomerular antigens. The mechanisms of mesangial damage in IgA nephropathy are not well known. Mesangial cells are capable of producing and releasing various lipidic and proteic mediators. The stimulation of mesangial cells, cultured in vitro by IgA or IgG immune complexes induced the release of PAF, PGE2 and superoxide anion. A better knowledge of the mechanism implicated in the abnormality of IgA immune regulation, as well as of the glomerular inflammation response could afford a new therapeutic approach to this nephropathy. PMID- 2249144 TI - [Counsel of the National Academy of Medicine on the rehabilitation of the Montchanin (Saone-et-Loire) waste site]. PMID- 2249145 TI - [A legal project concerning the rights and protection of persons hospitalized for mental disorders and the conditions of their hospitalization]. PMID- 2249146 TI - [Update on the epidemiology of hydatidosis. Hydatid echinococci: species; life cycles; epidemiologic consequences]. AB - Human hydatidosis results from infestation by two species of Echinococcus. (1) E. vogeli, the life-cycle of which occurs in amazonian forests and involves wild canidae and cuniculidae. (2) E. granulosus, which includes two geographical groups: (a) Northern group, with two sub-species E. g borelis and E. g. canadensis, the life-cycle of which is sylvatic and that are agents of a pulmonary hydatidosis which may affect Man. (b) "European" (actually cosmopolitan) form, with two sub-species: (1) E. q. equinus (equine strain) occurring between dogs and horses and unable to infect Man; (2) E. g. granulosus, with several strains and clones according to the species of their intermediate hosts and which are the agents of synanthropic or sylvatic life-cycles. Man may enter into some of these life cycles, but not into all of them: ovine strains, chiefly, but pig and camel strains also, have a zoonotic incidence. From these data, the author emphasizes the epidemiological features of human hydatidosis, which over-runs the classical rural one, resulting from the drog-sheep life cycle. PMID- 2249147 TI - [Mental health and war in Lebanon]. AB - This paper studies the effects of the war on the civilian and military lebanese populations from 1975 to 1987. A review of the literature on war psychiatry is presented as an introduction in order to estimate its applicability to Lebanon, and it seems that all the morbid conditions described in the different wars are to be found in Lebanon. A study on the military population was undertaken, focusing on the comparison of the morbid conditions before and during the war. It shows that war has led to a decrease of malingering and generalized anxiety disorders but to an increase of neurotic and psychotic reactions. A comparison of these conditions with those found in Vietnam shows a greater proportion of generalized anxiety and post-traumatic stress disorders among Marines in Vietnam. The milicians of the Lebanese Forces differ from the Lebanese Army soldiers by a higher proportion of antisocial personality disorders and anxiety neuroses. Among the civilian population war does not seem to have significantly modified in patient morbidity in the main psychotic, affective and neurotic diagnostic categories. Drug abuse whose frequency has considerably increased during the war is studied in detail. In conclusion, the author analyzes the factors having contributed to the relative psychological resistance of the Lebanese population. PMID- 2249148 TI - [The demand for use of hydroxypropyl starches and of phosphates of hydroxypropyl starches in human nutrition]. PMID- 2249149 TI - [Eulogy for Pierre Lepine (1901-1989)]. PMID- 2249150 TI - [Defense and illustration of a health examination in adolescents as observed in the course of secondary education]. AB - In France, children's health is carefully looked after by periodical examinations from birth to six years old. But the french children cannot have afterwards a systematic health examination during the course of their compulsory attendance at school, except those preparing a technical teaching. The author suggests that an examination during the first period of adolescence (between 11 and 15 years old) should be a vector of information very useful to subjects themselves and knowledge in Public Health not much documented at this stage. To assert this statement and draw useful conclusions, the Institut Regional pour la Sante de Tours, whose the author is the founder, and the departmental School Health Service have co-ordinated their actions for an examination on 56 classes in second forms (randomised among 321) of 1316 schoolchildren (662 boys-654 girls). This clinical, paraclinical and biological survey pointed out bad habits of nutrition, alcoholic drinks, smoking, excess of corpulence and blood pressure, visual and auditive trouble unknown or neglected, dental caries not treated, statics trouble and high hypercholesterolemia, as well. All these pathological elements are unknown and not taken over on the whole, at the present time. But these discoveries cannot really justify the systematic generalisation of an health examination, if, on the one hand, there is not an efficient follow-up that affects family physicians, pediatricians, local Health Educational Services, and, on the other hand, a short and mean-dated estimation. Such a completed and systematic examination could then be essential both from the individual benefit point of view and to the literature in Public Health (analytical and descriptive epidemiology). The author also refers to a similar study, as productive as the former, led one year before in the first form. Whatever the form--first or second ones--systematization of a good examination must fill the blank: it can be validly made by the coordinated actions of a dynamic School Health Service, a local partnership (bringing logistic, laboratory, data processing and physicians (general practitioners or pediatricians) for a medical and educational follow-up essential not only in the immediate future but with a view to a mean and long dated prevention. PMID- 2249151 TI - [The research of filaricides for the control of african onchocerciasis]. AB - Amongst several other chemical series, the epoxi and ethylenesulfonamides (which are more stable) have been selected after that we have shown good filaricidal activities on the Filaria Molinema dessetae. This has been confirmed on other models. Good activity was observed with O. gutturosa adult male in vitro, while microfilariae of O. lienalis were insusceptible to the selected compounds. The future of these products was discussed, in the prospect of their development and in relation with their mode of action and the other available pharmacological data. PMID- 2249152 TI - [Request for authorization to use as much natural mineral water as emerges from its source at La Verniere situated in Aires (Herault), after transportation to a distant site and purification]. PMID- 2249153 TI - Elderly oral premedication. PMID- 2249154 TI - A youthful perspective on research. PMID- 2249155 TI - Russian dentistry comes to Kenora. PMID- 2249156 TI - Oral cancer and precancer. AB - Oral carcinoma can be regarded as a largely preventable disease. Early recognition should be an attainable goal for most patients undergoing regular dental recall appointments. An understanding of the risk factors and of the characteristics of precancerous lesions can serve to heighten clinical sensitivity to oral SCC. Biopsies should be performed in all cases where the possibility of SCC exists; alternatively, patients should be referred to appropriate specialists for further evaluation. PMID- 2249157 TI - [Study on the causes of post-endodontic failures: a descriptive analysis of 198 cases of reoperation]. AB - In this article, a statistical analysis describes 198 cases of post-endodontic failures referred from private practitioners for surgical retreatments. Biopsies of these lesions showed that 68.18 per cent of them were identified as apical granulomas, 3.5 per cent as cysts, 16.16 per cent as epitheliated granulomas and 12.12 per cent as "other" cases. The two main groups of causes associated with these failures are: technical errors (55.05 per cent of the cases) and procedural mistakes (17.68 per cent). PMID- 2249158 TI - "Smiles tell secrets...". PMID- 2249159 TI - Getting the "feel" of it: the non-visual component of dimensional accuracy during operative tooth preparation. AB - The purpose of this study was to determine what portion of a dentist's dimensional accuracy in the use of the high-speed rotary handpiece for operative tooth preparation can be attributed to visual control during the preparation. Dental students in a performance simulation laboratory recorded an 87.5 per cent handpiece control accuracy during a maxillary occlusal preparation, using normal intraoral mirror vision. When visual contact was eliminated during preparation, the accuracy declined only 13 per cent, to 74.5 per cent. The results of this study lend support to the development and use of dental clinical simulations and approaches which encourage proprioceptive and other non-visual skills, in addition to visual skills, during preclinical and clinical dental education. PMID- 2249160 TI - An exploratory study on increases in masseteric muscle activity induced by caffeine. AB - In a crossover double blind experimental design, the nocturnal masseteric activity of 14 selected volunteers was evaluated by means of a portable electromyograph recording unit. The recordings lasted for a period of 16 days following ingestion of caffeine or placebo for five specific days each. There were no significant differences between caffeine or placebo on masseteric activity associated with bruxism. But when the two periods were compared, there was a tendency towards reduction of masseteric area activity and increase of stress levels in the second period of ingestion. PMID- 2249161 TI - Treatment of rapidly progressive periodontitis: a review and case report. PMID- 2249162 TI - Pioneers of prevention. PMID- 2249163 TI - A miniaturized vitrectomy system for vitreous and retinal biopsy. AB - The author has developed a miniaturized vitrectomy system and its accessories with the size of a 23-gauge needle. The hand-piece can be inserted inside the eye through a Ziegler knife track. This instrument can be used for "atraumatic" removal of vitreous biopsy specimens and for removal of small pieces of retina. The system also seems to have application in vitreous surgery in premature infants' eyes. PMID- 2249164 TI - Lens opacity as a predictor of visual field impairment due to cataract. AB - The contribution of cataract to the decrease of visual field in patients with glaucoma is difficult to ascertain. To attempt to quantitate the change in visual field due to cataract, we examined 27 eyes of 26 patients before and after cataract extraction. The examination consisted of measurement of best refraction with visual acuity, visual field testing with the pupil dilated, measurement of lens opacity, determination of the intraocular pressure, and evaluation of the character of the cataract before surgery and of the posterior capsule after surgery. The results reaffirmed the detrimental effect that cataract may have on the visual field but also showed that the heterogeneity of cataracts limits the usefulness of the lens opacity meter in quantitating the extent of visual field loss due to cataract. PMID- 2249165 TI - Orbital compartment syndrome. Direct measurement of orbital tissue pressure: 1. Technique. AB - Many disorders of the orbit produce an increase in intraorbital pressure, which may result in the development of an orbital compartment syndrome and visual loss. Traditionally, orbital tension is assessed clinically by indirect means based on retrodisplacement of the globe. The authors describe their experience with the "slit-catheter" technique for direct tissue pressure measurement as applied to the orbit. The preliminary results indicate that normal orbital pressure ranges from 3.0 to 6.0 mm Hg. In patients with Graves' orbitopathy the values ranged from 7.0 to 15.0 mm Hg. The results suggest that the technique may have many exciting possibilities as a clinical research tool in orbital disease, and its use will result in better understanding of orbital compartment syndromes. PMID- 2249166 TI - Possible significance of cilioretinal arteries in low-tension glaucoma. AB - Cilioretinal arteries arise from the short posterior ciliary artery circulation or directly from the choroidal circulation. The presence of a cilioretinal artery may in compromised discs steal flow from the peripapillary circulation and account for worsening glaucoma damage. We reviewed the records of 33 patients with unilateral cilioretinal arteries admitted for investigation of low-tension glaucoma. We looked for absolute difference between the affected and unaffected eyes as well as percent difference relative to the mean value for the two eyes and to the value for the unaffected eye in the following variables: mean defect, corrected loss variance or corrected pattern standard deviation, and adjusted neuroretinal rim area. No statistically significant differences were found. The mean disc area for the eyes with cilioretinal arteries was significantly larger than that previously reported for normal eyes. The results suggest that if vascular steal exists because of the presence of this artery, it is not of major clinical importance. PMID- 2249167 TI - Recession of the superior oblique tendon in A-pattern strabismus. AB - We performed 9 to 12 mm of recession of the superior oblique tendon for A-pattern strabismus in 10 patients. The average preoperative A-pattern measured 29.4 prism dioptres (PD), and the average pattern correction was 29.3 PD. All patients had a residual pattern of 6 PD or less (average 2.3 PD). No patient experienced significant underaction of the superior oblique, and other surgical complications, such as ptosis, Brown's syndrome, and laceration of the vortex vein or superior rectus, did not occur. The procedure corrected 14 to 40 PD of A pattern. The amount of pattern corrected was correlated with the size of the preoperative A-pattern but not with the total amount of recession done. No significant shift in esodeviation in primary position was noted in the patients who underwent only superior oblique recession. The procedure appears to be of particular value in patients with moderate superior oblique overaction. The advantages of recession of the superior oblique tendon include the potential for reversibility and reoperation, low risk of induced superior oblique palsy, allowance for asymmetric surgery and potential for adjustable suture technique. PMID- 2249168 TI - Angle-closure glaucoma as initial presentation of myelodysplastic syndrome. AB - A 57-year-old man presented with proptosis of the right eye and findings consistent with bilateral angle-closure glaucoma. Subsequent evaluation revealed severe bilateral uveal effusions and associated nonrhegmatogenous retinal detachments, which were felt to be related to orbital pseudotumour and associated scleritis. Hematologic studies were consistent with a diagnosis of myelodysplastic syndrome. Although myelodysplastic syndrome has been reported in one patient with orbital inflammation and myositis, to our knowledge ciliochoroidal effusion and secondary angle closure have not previously been reported in myelodysplastic syndrome. PMID- 2249169 TI - Nonpigmented congenital iris stromal cyst. AB - A nonpigmented iris stromal cyst was observed in the right eye of a 6-week-old girl. There was no past history of trauma or use of topical miotics, and the remainder of the ocular examination was normal. The pathophysiology and management of this rare developmental anomaly are controversial. PMID- 2249170 TI - Drug adverse reaction reports: an integral part of good ophthalmologic practice. PMID- 2249171 TI - [The mode of action of a nonpolyenic antifungal (desertomycin) produced by a strain of Streptomyces spectabilis]. AB - A metabolite with antifungal activity, of non polyenic macrolide structure, was extracted and purified from the culture supernatant of a soil-isolated Streptomyces spectabilis strain, BT 352. This product was found to be related to (or being) desertomycin. Six yeast and five filamentous fungus strains were used to determine minimum concentration of the metabolite that inhibits growth by 80% (IMC); it was established at 50 micrograms/mL for the fungi and at 100 micrograms/mL or more for the yeasts tested. Short-term genotoxicity tests showed no antifungal effect on the bacterial genome, and desertomycin at concentration levels of 100 micrograms/mL or more affected protein synthesis. The antifungal metabolite had no immediate inhibiting effect upon yeast respiration, even at high concentrations; however, the respiration activity of cells grown in the presence of subinhibiting doses and collected during their growth phase was reduced by as much as 40%. Saccharomyces uvarum spheroplast regeneration in a liquid medium containing desertomycin was inhibited at doses fivefold weaker than the IMC determined with intact cells. Contrary to amphotericin B, desertomycin subinhibiting doses do not modify, and if so lightly, the yeast latent phase or the spheroplast wall regeneration phase, thus indicating a fungicidal action. Moreover, following a 30-min contact with desertomycin subinhibiting and inhibiting doses, yeasts liberated potassium in large amounts, indicating that plasma membranes were affected. PMID- 2249172 TI - Study of the antigenic relationships between strains of Bacteroides, intermedius, B. melaninogenicus, B. corporis, and B. denticola revealed by immunoblotting with rabbit antisera. AB - Antigen profiles of saccharolytic oral black-pigmented Bacteroides have been developed by Western blotting. Visual comparisons indicated extensive cross reactions between B. intermedius, B. melaninogenicus, B. denticola, and B. corporis. Porphyromonas gingivalis, P. asaccharolyticus, and B. buccae showed less cross-reaction. Quantitation of antigenic similarity was made from densitometric scans. Calculation of the Jackard coefficient gave results of 33 72% similarity among the saccharolytic pigmented species, with the two homology groups of B. intermedius separated at 53%. Species were separated below 70%. Subtraction of the profile of a cross-reacting strain from that of the homologous strain also allowed quantitation of similarities. These similarities were lower; the range between species was 4-62%, although the two homology groups of B. intermedius still separated at 50 and 58%. Species were separated below 63%. Sera absorbed with a cross-reacting strain gave reduced reactions with the homologous strain and cross-reacting strains, indicating several common antigens among the four species. The species-specific antigens demonstrated by sera absorbed with cells of cross-reacting species were relatively few (3-6) compared with cross reacting antigens detected by non-absorbed sera (18-28). The method appears useful to quantitate antigenic similarities among Bacteroides species and strains and allows analysis and quantitation of individual humoral responses in animals to these bacteria. PMID- 2249173 TI - Prediction of the halothane (Hal) genotypes by means of linked marker loci (Phi, Po2, Pgd) in Quebec Landrace pigs. AB - Quebec Landrace pigs (n = 896) were halothane tested and blood samples were taken for the determination of Phi, Po2 and Pgd phenotypes. The incidence of the halothane positive pigs was 5.3%. The frequencies of the favorable alleles PhiA, Po2S and PdgA were respectively 29.2%, 39.6% and 64.4%. The highest linkage disequilibrium was found between Hal-Phi (0.0606) followed by Hal-Pgd (0.0428) and Hal-Po2 (-0.0308). Alleles PhiB, PgdB and Po2F were associated respectively with 97%, 81% and 74% of Haln haplotypes. It was concluded that a selection in order to increase the favorable marker loci PhiA and PgdA would reduce the Haln frequency in Quebec Landrace pigs. PMID- 2249174 TI - Fragment Bb of bovine complement factor B: stimulatory effect on the microbicidal activity of bovine monocytes. AB - We have previously shown that the Bb fragment of bovine complement factor B activates bovine monocytes and neutrophils. The activation was demonstrated by the enhanced uptake of 3H-deoxyglucose. To investigate the potential effect of fragment Bb on the microbicidal activity of bovine monocytes, a direct method was used. This method involves an initial ingestion period at 37 degrees C followed by repeated washing. The decrease in the total number of viable intracellular Staphylococcus aureus during the reincubation of the bacteria with bovine monocytes determines the intracellular killing. Maximal intracellular killing was seen when the monocytes containing the ingested S. aureus was incubated with fresh bovine serum (mean +/- SEM = 73.4 +/- 1.4%). On incubation of the monocytes, containing the ingested bacteria with heat-inactivated bovine serum, 32.5 +/- 0.7% of the intracellular bacteria were killed. When affinity-purified bovine factor Bb was added to the heat-inactivated serum, the intracellular killing capacity was almost restored (65.8 +/- 1.5%). When monocytes were incubated with medium alone, they killed 22.4% of the intracellular microorganisms. When fragment Bb (25 micrograms/mL) was added to the medium, the intracellular killing of S. aureus doubled (46 +/- 1.29%). We conclude that the Bb fragment of bovine complement factor B stimulates bovine monocytes in their microbicidal activity. PMID- 2249175 TI - Hematological changes in calves exposed to a mixture of lipopolysaccharide and crude leukotoxin of Pasteurella haemolytica. AB - The purpose of this investigation was to determine if culture supernatants of Pasteurella haemolytica containing crude leukotoxin and lipopolysaccharide (CLCL) causes disseminated intravascular coagulopathy (DIC) when injected into calves. The effect of intraduodenal (ID) exposure followed by a subsequent subcutaneous (SC) inoculation of either heat-treated or untreated CLCL was evaluated. The relative contribution of the crude leukotoxin and lipopolysaccharide (LPS) to the virulence of P. haemolytica was evaluated. One group of calves received an ID inoculation of CLCL followed two weeks later by a SC inoculation of CLCL; one group received an ID inoculation of tissue culture medium followed two weeks later by a SC inoculation of CLCL; and a third group received an ID inoculation of CLCL followed two weeks later by a SC inoculation of heat-treated CLCL. Hematological parameters used to evaluate DIC included white cell count, platelet count, neutrophil number, fibrinogen, fibrin degradation products, one stage prothrombin time (OSPT), activated partial thromboplastin time, body temperature and clinical signs. Each parameter was measured in calves at 0, 2, 4, 6, 12 and 24 h following the SC inoculation of CLCL. Each group had significant changes over time in all parameters except body temperature. Calves that received a SC inoculation of heat-treated CLCL had smaller changes in all parameters except OSPT compared to the other groups. Results suggest that the LPS and leukotoxin of P. haemolytica exert additive effects on the coagulation cascade and number of peripheral leukocytes, and that the ID inoculation of CLCL does not affect the response of calves to a SC inoculation of toxin. PMID- 2249176 TI - Restriction endonuclease analysis of porcine Pasteurella multocida isolates from Quebec. AB - We have used restriction endonuclease analysis (REA) of genomic DNA to classify porcine Pasteurella multocida isolates with similar capsular and somatic serotypes, and to monitor the distribution of isolates from 12 different herds in Quebec. Within herds, P. multocida isolates of similar capsular and somatic serotypes showed similar REA fingerprints. Between herds, some isolates had similar REA fingerprints. However, differences in REA enabled subtyping of many P. multocida isolates with the same antigen types. Our data indicate that REA would enable accurate epidemiological typing of P. multocida in conjunction with classical capsular and somatic typing. PMID- 2249177 TI - Serodiagnosis of pleuropneumonia using enzyme-linked immunosorbent assay with capsular polysaccharide antigens of Actinobacillus pleuropneumoniae serotypes 1, 2, 5 and 7. AB - Capsular polysaccharide antigens of serotypes 1, 2, 5 and 7 of Actinobacillus pleuropneumoniae were used in enzyme-linked immunosorbent assays (ELISAs) to test sera from experimentally infected and field pigs. Specific reactions were found in sera of experimental pigs with antigens of serotypes 1, 5 and 7 whereas the serotype 2 antigen was cross-reactive. A 1:200 serum dilution was used for testing of 300 sera from 21 swine herds in southern Ontario. Cases of pleuropneumonia had occurred in 11 of these herds, but not in the others. The negative cut-off value was the mean optical density at 405 nm (OD405) + three standard deviations (SD) for 16 negative reference sera. Sera from four pigs naturally infected with Actinobacillus suis were tested and found to react to varying degrees with each of the antigens. Therefore a second cut-off value was determined as the mean OD405 + 2 SD for the A. suis sera. Sera which, in the ELISA produced OD readings above the latter cut-off were considered positive for antibodies to A. pleuropneumoniae; those which were lower than the former cut-off were considered negative. Readings between the two cut-off values may have been due to low positive titers or cross-reactivity, possibly with A. suis, and could not be used to predict pleuropneumonia. Of the pleuropneumonia-free herds, none had positive reactors to serotypes 5 or 7, whereas one and two herds had positive reactors to serotypes 1 and 2, respectively. Of the pleuropneumonia positive herds, six had positive reactors to serotype 1, one to serotype 2, four to serotype 5, and eight to serotype 7. PMID- 2249178 TI - Reproductive failure in mink and ferrets after intravenous or oral inoculation of Campylobacter jejuni. AB - Four pregnant mink and seven pregnant ferrets, including five with previous exposure and specific antibody, were injected intravenously with 10(8)-10(10) colony-forming units of Campylobacter jejuni. All 11 pregnancies failed 1-16 days after infection, with results ranging from fetal resorption to expulsion of dead or premature living kits. In every case, uterine contents (placenta, uterine fluid and/or kits) were culture-positive for C. jejuni. Three pregnant mink and nine pregnant ferrets, including four with previous exposure and antibody, were fed 10(9)-10(11) C. jejuni. Two of the mink aborted; kits of all three were culture-positive, but those of one female survived. Seven of the nine ferrets aborted, with two having culture-positive uterine contents. None of 28 uninfected ferret control pregnancies ended in abortion. The most prominent histological feature observed was severe placentitis, which appears to be a more likely cause of Campylobacter-induced abortion than direct pathogenic effects on infected kits. These results suggest that infection of mink or ferrets with C. jejuni during pregnancy poses a serious risk of reproductive failure, even for previously exposed females. PMID- 2249179 TI - The epidemic of foot-and-mouth disease in Saskatchewan, Canada, 1951-1952. AB - The epidemic of foot-and-mouth disease in Saskatchewan in 1951 and 1952 was studied in order to determine origins of outbreaks and methods of spread. The epidemic was initially considered to be vesicular stomatitis and foot-and-mouth disease was not recognized until February 1952, three months after the initial infection. The reports prepared at that time were reviewed in order to obtain details of the numbers of animals infected and the source and date of infection for the outbreaks. Methods of spread were rated according to their likelihood. The introduction of infection by an immigrant through his clothes as well as by sausage was possible. The sequence of events from the first outbreak to the spread from a feedlot/packing plant and from a dairy farm, which failed to report the disease, were clarified. Methods of spread included movement of animals, animal products and people and the airborne route. Milk delivery and artificial insemination did not result in spread of infection. The quarantine of affected farms reduced spread by animals and deterred visits by people. The original diagnosis of vesicular stomatitis was due to misinterpretation of a lesion in an inoculated horse. Laboratory tests established the presence of foot-and-mouth disease. The limited extent of the epidemic, despite the delay in diagnosis, is attributed to (i) the low density of cattle, (ii) few infected pigs and hence less airborne virus and (iii) absence of waste food feeding and milk collection in addition to the limited quarantine imposed. PMID- 2249180 TI - A morphometric study of the canine colon: comparison of control dogs and cases of colonic disease. AB - The microstructure of the canine colon was described morphometrically. The artifacts induced by administration of enemas and biopsy technique were studied by comparing biopsy specimens to tissues obtained at necropsy from 15 normal dogs. Biopsies from control dogs and clinical cases of colonic disease were then evaluated quantitatively, and histological abnormalities which might clarify mechanisms underlying large bowel dysfunction in the dog were sought. In control dogs, gland length and diameter, epithelial, goblet cell and mucosal mast cell numbers, and intraepithelial lymphocyte and mitotic indices were remarkably uniform throughout the colon. Minor variations were found in the proximal and distal regions of the colon. An apparent shortening of glands, and a reduction in mucous goblets and intraepithelial lymphocytes in biopsies were attributed to suboptimal orientation and irritation caused by enemas. The only significant difference from controls identified by morphometric analysis of biopsies from clinical cases was fewer epithelial cells lining longitudinal sections of glands. It was concluded that failure to identify morphometric variations in the colonic mucosa of clinical cases might reflect either a biased, homogeneously mild clinical syndrome in this group, or the possibility that in many of the clinical cases, a functional rather than physical abnormality was involved. The proprial inflammatory cell population was not examined quantitatively; further investigation of this component is merited. PMID- 2249181 TI - Postmortem eyefluid analysis in dogs, cats and cattle as an estimate of antemortem serum chemistry profiles. AB - This study was carried out to determine the diagnostic usefulness of postmortem eyefluid analysis in estimating antemortem concentrations of serochemical constituents. A total of 31 cattle, 18 dogs and 22 cats were selected from routine elective euthanasia submissions to a diagnostic laboratory. For all cases, a biochemical profile, including determinations for electrolytes, glucose, urea, creatinine, enzymes, cholesterol, bilirubin, protein and osmolality was performed on antemortem serum, and postmortem aqueous and vitreous humors at 0 and 24 h incubation periods. The association between serum and postmortem eyefluid chemistry values was examined using simple linear regression. A strong correlation between serum and postmortem eyefluid urea and creatinine concentrations was demonstrated in the three species examined over a 24 h postmortem interval. We concluded that an accurate estimate of antemortem serum urea or creatinine can be made from the analysis of aqueous or vitreous fluid at necropsy. An estimation of antemortem serum electrolytes (including calcium in cattle) cannot be made with a high degree of accuracy due to the amount of variability in the relationship between serum and eyefluid electrolyte values. For large molecules such as proteins, enzymes, cholesterol and bilirubin there was very poor correlation between serum and eyefluid values. PMID- 2249182 TI - Use of electromyography for the diagnosis of equine hyperkalemic periodic paresis. AB - The use of electromyography (EMG) as a diagnostic aid for equine hyperkalemic periodic paresis (EHPP) was investigated in seven affected and seven control horses. Affected horses were confirmed positive for EHPP either by elevated serum potassium concentration with clinical signs of myotonia, or by inducing hyperkalemia and clinical signs using oral potassium chloride challenge. All horses were asymptomatic at the time EMG was performed, using bipolar fine wire needle electrodes. The myopotentials were recorded on magnetic tape and displayed on paper charts for analysis. Insertional and resting activity were recorded from the right supraspinatus, triceps, extensor carpi radialis and gluteal muscles in standing horses. Myotonic discharges were seen in six of seven affected horses but not in any of the controls. All seven affected horses and two control horses had prolonged insertional activity. Five out of seven affected horses and one control horse displayed spontaneous motor unit discharges unrelated to recording electrode movement. Myoelectrical potentials containing closely timed muscle potentials, i.e. doublets, were found in all affected horses, with four of seven affected horses also showing triplets. These potentials were not observed in any of the controls. No obvious difference in activity was observed among the four muscle sites tested. It is concluded that EMG is a safe and useful tool for diagnosing EHPP in horses not currently displaying clinical signs. Myotonic discharges and doublets appear to be the most diagnostically significant electromyographic abnormalities in EHPP affected horses. PMID- 2249184 TI - The Patterns of Care Outcome Study for cancer of the uterine cervix. Results of the Second National Practice Survey. AB - This report summarizes the outcome results of the Patterns of Care Study (PCS) of cancer of the uterine cervix from 565 patients treated in 1978. The 5-year survival with no evidence of disease was: Stage I, 74%; Stage II, 56%; and Stage III, 33%. The 5-year local in-field failure rate was: Stage I, 12%, Stage II, 27%; and Stage III, 51%. Extent of parametrial involvement, unilateral versus bilateral, may be important in determining survival and local failure. The four year actuarial survival was 58% for unilateral involvement versus 47% for bilateral (P = 0.06), and the local failure rate was 32% for unilateral versus 45% for bilateral (P less than 0.05). When analyzed by stage, patients with Stage IIb disease with unilateral parametrial involvement showed a trend toward improved survival and decreased local failure compared with those with bilateral Stage IIb cancers (P = 0.1). The use of intracavitary irradiation significantly improved survival and reduced local failures. Furthermore, the number of intracavitary applications was important. When two or more intracavitary applications were used compared with one application, local in-field failure was significantly reduced, 29% versus 17% at 4 years (P less than 0.001), and four year survival was improved, 60% versus 73% (P = 0.01). The four-year actuarial rate of major complications depended on the stage: Stage I, 8%; Stage II, 15%; and Stage III, 13%. There was a statistically significant increase in major complications in patients undergoing laparotomy for staging versus no laparotomy 23% versus 11% at 4 years (P less than or equal to 0.01) and a trend toward increased major complications in patients who were thin or had prior abdominal surgery. This study confirmed the stage-dependent outcome of treatment of cancer of the uterine cervix with radiation and indicated that further division of Stage IIb to indicate prognostic significance of unilateral or bilateral parametrial involvement may be warranted. This study also confirmed the importance of intracavitary radiation in optimizing control established by the 1973 PCS. It further suggests that where possible, two intracavitary insertions may yield better results than one insertion. PMID- 2249183 TI - Vaccinia recombinant virus expressing the rabies virus glycoprotein: safety and efficacy trials in Canadian wildlife. AB - Twenty-six meadow voles (Microtus pennsylvanicus), ten woodchucks (Marmota monax), thirteen grey squirrels (Sciurus carolinensis), thirteen ring-billed gulls (Larus delawarensis), six red-tailed hawks (Buteo jamaicensis) and eight great horned owls (Bubo virginianus) received vaccinia virus recombinant expressing the rabies virus glycoprotein (V-RG) by direct instillation into the oral cavity. Each of ten coyotes (Canis latrans) received the virus in two vaccine-laden baits. Several voles and most of the gulls died from diseases unrelated to vaccination during the observation period, but all other animals remained healthy and survived. These deaths from causes other than vaccination and the absence of any lesions suggestive of vaccinia infection indicate that it is unlikely that any animal suffered or died as a result of V-RG administration. In addition several animals showed an unexpected high level of rabies neutralizing antibodies. PMID- 2249185 TI - The influence of autologous lymphokine-activated killer cell infusions on the toxicity and antitumor effect of repetitive cycles of interleukin-2. AB - Twenty patients with refractory malignancies were treated with a protocol evaluating the addition of ex vivo-activated autologous lymphokine-activated killer (LAK) cells to a clinically tolerable interleukin-2 (IL-2) regimen (four weekly cycles of human recombinant IL-2 at 3 x 10(6) U/m2/day by continuous infusion for 4 days/week). Sixteen patients completed their induction month of therapy, two had a partial response, six had stable disease, and eight had progressive disease. Four patients had clinical toxicity preventing completion of the induction month of therapy, and one of these patients died during therapy. Significant clinical toxicities included decreased performance status, weight gain, catheter-related thromboses, infectious complications, fever, hypotension, and dyspnea or hypoxemia requiring oxygen. Thus, the addition of LAK cell infusions to this IL-2 regimen did not cause a noticeable change in antitumor response rate but did not cause more severe toxicity. PMID- 2249186 TI - Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. AB - Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity. PMID- 2249187 TI - Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity. AB - Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs. PMID- 2249188 TI - Conservative surgery and radiation therapy for soft tissue sarcoma of the wrist, hand, ankle, and foot. AB - Seventy-eight patients with soft tissue sarcoma (STS) arising in the distal extremities--wrist, hand, finger, ankle, foot, and toe--who were treated with conservation surgery and radiation therapy were studied retrospectively with respect to survival, local recurrence, functional limb preservation, complications, and distant metastasis. After a median follow-up of 7.9 years, actuarial 5-year and 10-year survival rates were 80% and 69%, respectively, and disease-free rates were 61% and 51% at the same times. Actuarial local control rates were 80% and 74% at 5 and 10 years, respectively. Fifteen patients (19%) had local recurrence, but 12 of these were salvaged. Ultimately, 53 patients (68%) retained a normal or fairly normal extremity, six (8%) needed amputation for complications, and 13 (17%) needed amputation to control recurrent disease. The functional outcome was significantly better for patients with upper extremity lesions than for those with lower extremity tumors; even for the latter, this treatment strategy was preferable to amputation. The incidence of hematogenous metastases from distal extremity sarcomas depends on the size of the primary tumor. It was concluded that conservation surgery and radiation therapy (XRT) is an acceptable treatment strategy for STS arising in distal extremities; it yielded a high rate of disease control and functional limb preservation. PMID- 2249190 TI - A standard dose of radiation for "microscopic disease" is not appropriate. AB - Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = [1 - Pocc x (1 - e-Ni x (SF2)D/2)]A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogens in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose. PMID- 2249189 TI - Multiagent chemotherapy in relapsed acute lymphoblastic leukemia in children. AB - Twenty-seven evaluable children with early first bone marrow relapse of acute lymphoblastic leukemia were treated with an intensive induction/consolidation and ongoing maintenance therapy. Induction therapy consisted of a 35-day course of daunomycin, vincristine, and prednisone, immediately followed by teniposide, cytosine arabinoside (Ara-C), and L-asparaginase. Intrathecal methotrexate, hydrocortisone, and Ara-C were given through the induction/consolidation phase. Twenty-three of 27 patients achieved remission by the end of induction/consolidation. Maintenance with the same drugs in a modified dosage schedule continued for approximately 2 years. A small subgroup of patients who were M3 at day 35 but M1 at day 56 (end of induction/consolidation) and had a cumulative event-free survival (EFS) of only 0.40 at 6 months, all had relapsed by 15 months. However, the EFS for M1 patients by day 35 and maintained on chemotherapy was 0.64 at 12 months and 0.32 at 30, 36, and 48 months, respectively. Although good reinduction and remission duration rates at 12 to 24 months were achieved and an apparent plateau in survival occurs at 30 months, fall-off in survival would not be unexpected with probably less than 20% alive after 5 years. PMID- 2249191 TI - Primary central nervous system lymphoma in a pediatric patient with acquired immune deficiency syndrome. Treatment with radiation therapy. AB - Primary central nervous system (CNS) lymphoma, an otherwise rare pediatric tumor, has been reported with increasing frequency in children with acquired immune deficiency syndrome (AIDS). With current therapy, the outcome of this disease is invariably fatal. The authors present a case of primary CNS lymphoma in a 3.5 year-old girl with AIDS who received treatment with total brain irradiation. After treatment, the patient's mental status improved, the seizures resolved, and she had no further progression of her neurologic symptoms until she died of pneumonia 6 months later. The autopsy revealed a necrotic mass at the site of the original tumor. The brain stem and spinal cord, unirradiated, contained lymphomatous lesions. The patient had extensive fibrinoid necrosis and leukoencephalopathy that were consistent with radiation-induced CNS damage. Coexisting AIDS encephalopathy also contributed to the patient's CNS injury. Effective palliation of CNS lymphoma in children with AIDS may be obtained with cranial irradiation. Pediatric AIDS patients may show more severe tissue effects from irradiation than unaffected children. PMID- 2249192 TI - 131I treatment of thyroid papillary carcinoma in a patient with renal failure. AB - Procedures for 131I ablation in renal failure are not known. In one patient receiving dialysis, detailed dosimetry and health safety aspects were obtained. The results showed insignificant contamination of equipment, but a surprisingly significant reduction in biologic half-life of 131I due to efficient dialysis extraction. The data indicate that 131I ablation can be done safely and easily during dialysis but that much higher 131I doses must be used to achieve equivalent results to those obtained in patients with normal renal function. PMID- 2249193 TI - The interplay of local and distant control in the cure of cervical cancer. AB - From 1978 to 1986, 183 women with cervical cancer received definitive radiation therapy after extraperitoneal surgical staging. Relapse-free rates were strong functions of pelvic lymph node metastases and cervical size. The recurrence distribution consisted of 4% isolated local, 13% isolated distant, and 17% combined local and distant failures. With the assumption of independent local and distant failure probabilities, Suit et al.'s method was extended to assess potential improvement in cure attainable with perfect local and distant control, yielding local (LSA) and distant (DSA) survival advantages of 17% and 28%. Various subsets of clinical stage, cervical size, pelvic node metastases, periaortic metastases, and peritoneal metastases had LSA from 12% to 27% and DSA from 12% to 71%. For any prognostic group, LSA never exceeded DSA, showing that effective systemic therapy would have a greater impact on improving survival than would advances in local and regional tumor control. Therapeutic implications and limitations of the extended LSA-DSA model are discussed. This form of analysis can be used to guide the intensity of local and distant treatment to maximize the cure of the patient with cancer. PMID- 2249194 TI - The role of elective lymph node dissection in the management of patients with thick cutaneous melanoma. AB - A retrospective search of patients seen at the Duke Melanoma Clinic from 1970 to 1986 identified 308 clinically Stage I patients, with 4.0 to 10.0 mm cutaneous melanomas. Five-year and ten-year survival was 56% and 43%, respectively. Elective lymph node dissection (ELND) was done in 116 patients (37.7%); there was no difference in disease-free interval (DFI) or survival between these patients versus patients treated with wide excision only (P = 0.9). Thirty-two patients (27.6%) had pathologically positive nodes on ELND. These patients had a shorter DFI (P = 0.05) and survival (P = 0.03) compared with patients with negative node dissections. When further divided by Breslow's thickness, this difference persisted in patients with 4.0 to 6.0 mm lesions (P = 0.01). However, for thicker lesions (greater than 6.0 mm), there was no difference in survival between the node-negative and node-positive groups (P = 0.9). The mean follow-up was 7.1 years. Elective lymph node dissection was not done in 192 patients; 78 of these recurred first in the regional nodes. These 78 patients were compared with the 32 patients who had pathologically positive nodes by ELND to see if patient survival was improved by early removal of nodal disease. There was no difference in DFI (P = 0.5) or survival (P = 0.3) between these two groups. It is concluded that ELND may provide prognostic information for patients with thick cutaneous melanomas. However, there was no change in DFI or ultimate survival when patients were followed, and nodes removed when clinically positive. The authors do not recommend ELND for patients with thick melanomas because the risk of distant metastases outweighs any benefit of regional node dissection. PMID- 2249195 TI - Endoscopic and radiographic evaluation of the murine colon. AB - Endoscopic and radiographic techniques have not been widely applicable in the evaluation of chemically induced murine colon cancer. The authors investigated methods of cleansing the rat colon and refined endoscopic and radiographic techniques. They compared total colonoscopy (TC) and air-contrast (ACBE) and single-contrast barium enema (SCBE) findings with those obtained at necropsy in rats with 1,2-dimethylhydrazine (DMH)-induced colon cancer. Gastrograffin enemas with bisacodyl suppositiories showed complete evacuation of solid feces. Sprague Dawley rats treated with DMH had their colons cleansed and then underwent TC (5.0 mm Olympus bronchoscope) and either SCBE or ACBE. Colonoscopy and ACBE were equally sensitive (81.5% and 76.3%, respectively), although SCBE was significantly insensitive in identifying lesions (P less than 0.001). This study demonstrates that: (1) mechanical cleansing of the rat colon is feasible, (2) TC and barium radiology can be done routinely after mechanical cleansing, and (3) TC and double-contrast BE are sensitive in identifying colon lesions. These techniques will provide a means for manipulation of murine tumors and in vivo surveillance. PMID- 2249196 TI - Immunohistochemical differentiation of basal cell epithelioma from cutaneous appendages using monoclonal anti-glycoprotein antibody TNKH1. Its application in Mohs' micrographic surgery. AB - TNKH1, which was primarily developed to detect differentiated melanocytic tumor cells, was found to recognize basal keratinocytes of hair follicle and some basal keratinocytes of human epidermis. Thus, TNKH1 decorated the basal cells of following structures: epidermis (39 of 54, only part of each specimen [OPES]), upper hair follicle (one of 24, OPES), lower hair follicle (21 of 21, very high rate of each specimen [VHES]), sebaceous duct (14 of 15, VHES), sebaceous gland (ten of 14, germinative cells near duct), eccrine duct (three of 19, OPES). Epithelial tumors, considered to be derived from or differentiating toward hair follicle such as trichilemmoma (one of one, VHES) and basal cell epithelioma (BCE) (32 of 32, VHES) were labeled not only in the peripheral cells but in their entirety. On the other hand, epidermal tumors, such as seborrheic keratosis (ten of 11, OPES), actinic keratosis (two of three, OPES), and squamous cell carcinoma (one of two, OPES), showed an irregular peripheral basal cell staining as in normal epidermis. The apocrine sweat apparatus and eccrine secretory portion were negative. Eccrine ductal tumors such as syringoma (two tested), eccrine acrospiroma (one), and eccrine carcinoma (two) were TNKH1 negative. Taking advantage of this total labeling of BCE versus peripheral labeling of the hair follicle, the authors could distinguish BCE tissue from other structures clearly. Among confusing structures the upper hair follicle and the eccrine duct were excluded easily because of their negative staining with TNKH1. The lower hair follicle was TNKH1 positive but only in the outer basal layer, whereas the BCE was TNKH1 positive in its entire basaloid cells. The result indicated that TNKH1 will be a useful antibody in Mohs' micrographic surgery. PMID- 2249198 TI - Expression of placental alkaline phosphatase in gastric and colorectal cancers. An immunohistochemical study using the prepared monoclonal antibody. AB - The authors developed monoclonal antibodies (MoAb) against human placental alkaline phosphatase (PLAP). Four specific MoAb reacting only with PLAP and two nonspecific MoAb reacting equally with isozymes of alkaline phosphatase (hepatic, intestinal, and placental) were obtained. Immunohistochemical staining with the specific MoAb showed that the cell membrane and cytoplasm of cancer cells were stained in gastric and colorectal carcinoma. The incidence of PLAP positivity was 23% (25 of 107) of all gastric carcinomas. Among gastric carcinomas, the 42% (13 of 31) positivity of highly differentiated carcinoma (papillary adenocarcinoma and well-differentiated tubular adenocarcinoma) was a significantly higher rate than that found in poorly differentiated carcinoma (poorly differentiated adenocarcinoma and signet-ring cell carcinoma, five of 41, 12%). The incidence of PLAP positivity was 11% (four of 35) in colorectal carcinoma. In contrast, gastric adenoma, intestinal metaplasia, and noncancerous tissue adjacent to cancer did not show staining. These results indicated that expression of PLAP was apt to occur in more highly differentiated gastric carcinoma and was highly specific for carcinoma in the gastrointestinal tract, although its incidence was not high. PMID- 2249197 TI - Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks. AB - This investigation examined the correlation between Helicobacter pylori (HP) infection, as reflected in immunoglobulin G serum antibodies, and the risk of gastric cancer. Serum samples were obtained from populations with contrasting gastric cancer risks. The highest prevalence of HP infection, 93%, was observed in the adult population at highest gastric cancer risk, the residents of Pasto, Colombia. In the lower risk Colombian city of Cali, a 63% overall prevalence rate was found. Both children and adults were sampled in New Orleans, Louisiana, where gastric cancer rates are high for blacks but not for whites. The prevalence of HP infection was significantly higher in black than in white adults, 70% versus 43%, P = 0.0001. A higher prevalence was also detected in black compared with white children, 49% versus 32%, P = 0.01; however, an even greater disparity was noted when comparing children from two hospitals, regardless of race, which serve different socioeconomic groups. A prevalence rate of 54% was found at Charity Hospital compared with 24% (P = 0.0001) at Children's Hospital. Our findings indicate that socioeconomic conditions, known to influence gastric cancer risk, are also important determinants of HP infection. PMID- 2249199 TI - Prognostic significance of type IV collagen and laminin immunoreactivity in urothelial carcinomas of the bladder. AB - Invasion of a carcinoma involves the degradation and penetration of the subepithelial basement membrane (BM). This phenomenon might be used for histopathologic evaluation of neoplasms of the bladder. The authors studied the clinicopathologic data and tissue specimens of 125 cases of urothelial carcinomas collected prospectively. Penetration of the BM was evaluated by immunohistochemical staining of the BM components laminin and type IV collagen. The use of this parameter as a prognostic indicator in bladder cancer was assessed. The 5-year survival rate of patients having tumors with an interrupted or absent BM was significantly lower than that of patients having tumors with an intact BM. The rate of progression was greater in tumors with an interrupted or absent BM than in tumors with an intact BM. No association was found between BM status and recurrence. However, a significant correlation between tumor stage and BM staining was found. A correlation was also found between ploidy and BM staining as well as between histologic grade and BM staining pattern. When evaluating histologic grade, stage, ploidy, age, and BM score as prognostic parameters, the stage of bladder carcinomas turned out to be the most important factor in predicting the survival rate and the progression-free survival. However, BM staining was found to be of value for early identification of microinvasion and is helpful for correct staging of urothelial carcinomas. PMID- 2249200 TI - Primary breast lymphoma. An immunohistologic study of 20 new cases. AB - Primary malignant lymphomas of the breast (PBL) are uncommon. The authors report the clinical, histologic, and immunoperoxidase findings on 20 cases recorded at the Alberta Cancer Registry over the last 23 years. These cases were then added to material on 257 cases abstracted from the literature and analyzed. It was found that there are two clinicopathologic types of PBL. The first affects pregnant or lactating women with bilateral, diffuse disease, is rapidly fatal, and corresponds histologically to a Burkitt's-type lymphoma. The second is unilateral at presentation and afflicts a broad age range, but primarily older women. This has a variable course only part of which is predicted by histologic grade and stage. Tumor size, treatment, and side of presentation were not found to be significant prognostic factors. Histologically, these tumors can be grouped into large cell B-cell lymphomas, monocytoid B-cell lymphomas (MBCL), and undifferentiated, some of which may be T-cell. Evidence suggesting that the MBCL of breast are the equivalent of the malignant lymphomas of the mucosa-associated lymphoid tissues (MALT) is reviewed. The breast is a hormone-dependent member of the MALT and therefore it is interesting that two of these tumors were strongly positive for estrogen receptors. PMID- 2249201 TI - Primary malignant lymphomas of the spleen. A morphologic and immunohistochemical analysis of 17 cases. AB - Seventeen cases of primary malignant lymphoma of the spleen (PMLS) were identified among 500 splenectomy specimens showing involvement by Hodgkin's disease or non-Hodgkin's lymphoma. All PMLS represented non-Hodgkin's lymphoma and most of them were of B-cell origin. In two cases PMLS were associated with hamartomas of the spleen (splenomas). Histologic and immunohistochemical studies did not reveal any differences between PMLS and disseminated malignant lymphomas with splenic involvement with regard to morphologic features, immunophenotype, host cell infiltrates, or proliferation activity. The reasons for the infrequent occurrence of primary lymphomas in the spleen may not be sought in a special immunophenotype of PMLS, a vigorous host response in the spleen, or in a lower proliferation activity of splenic lymphomas. PMID- 2249202 TI - Estrogen receptor localization in normal and neoplastic epithelium of the uterine cervix. AB - To investigate the estrogen receptor (ER) status of cells during carcinogenesis of the uterine cervix, the immunohistochemical reactivity for a monoclonal anti ER antibody (H 222) was studied in 26 normal cervical specimens, 21 cases of cervical intraepithelial neoplasia (CIN), and 21 cases of invasive cervical carcinoma. In addition, the presence of human papillomavirus (HPV) DNA (types 6/11, 16/18, or 31/33/35) was analyzed by in situ hybridization. In the normal cervix, basal cells of the squamous epithelium, metaplastic cells, and endocervical glandular cells were ER positive. In contrast, neoplastic cells of CIN (17 of 21 cases) and invasive carcinoma (19 of 21 cases) were ER negative. The remaining four cases of CIN and two cases of invasive carcinoma were focally ER positive. The HPV DNA analysis revealed that HPV DNA in ER-negative cases was either types 16/18 or undetectable, but all ER-positive neoplasms contained HPV DNA types 31/33/35. These results suggest that most neoplastic cells in CIN and invasive cervical carcinoma lose their ER expression and that this may be related to the HPV DNA types which they possess. PMID- 2249203 TI - Chondrolipoangioma. A cartilage-containing benign mesenchymoma of soft tissue. AB - The clinical and pathologic features of four cases of benign mesenchymoma in which mature cartilage represented the predominant component are reported. The distinctive histologic feature in all four cases was a lobular proliferation of cartilaginous tissue exhibiting a spectrum of hyaline cartilage, fibrocartilage, myxoid cartilage, and cartilage with ossification and even bone marrow formation, intimately associated with mature adipose tissue and vascular elements. The localization of these tumors was in the proximity of a bone, but not attached to the periosteum or in continuity with a joint. Because these lesions may be mistaken for other cartilaginous neoplasms of soft tissue, recognition of this entity has potentially important diagnostic and therapeutic implications in that mutilating surgery may be avoided. PMID- 2249204 TI - Recovery of morphine from a controlled-release preparation. A source of opioid abuse. AB - MS-Contin (Purdue-Fredrick, Norwalk, CT) is a controlled-release preparation of morphine sulfate that has demonstrated efficacy in the management of chronic cancer pain problems. It has recently come to the attention of the authors that MS-Contin represents a potential source of opioid abuse through the extraction and intravenous injection of the morphine from this preparation. The authors describe a simple aqueous extraction method that was used to quantitatively determine the extent to which morphine could be obtained from MS-Contin tablets. PMID- 2249205 TI - Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities. AB - Ninety-seven children who were diagnosed with acute lymphoblastic leukemia before 10 years of age and treated with chemotherapy alone, chemotherapy plus 1800-cGy cranial irradiation (RT), or chemotherapy plus 2400-cGy RT were evaluated for effects of therapy on dentofacial development. All patients were seen at least 5 years postdiagnosis. Dental abnormalities were determined from panoramic radiographs, and craniofacial evaluations were made from lateral cephalometric radiographs. Ninety-one (94%) of all patients and 41 (100%) of patients younger than 5 years of age at diagnosis had abnormal dental development. The severity of these abnormalities was greater in children who received treatment before 5 years of age and in those who received RT. Observed dental abnormalities included tooth agenesis, arrested root development, microdontia, and enamel dysplasias. Craniofacial abnormalities occurred in 18 of 20 (90%) of those patients who received chemotherapy plus 2400-cGy RT before 5 years of age. Mean cephalometric values of this group showed significant deficient mandibular development. The results of this study suggest that the severity of dentofacial-developmental abnormalities secondary to antileukemia therapy are related to the age of the patient at the initiation of treatment and the use of cranial RT. PMID- 2249206 TI - Clinical and prognostic assessment of patients with resected small peripheral lung cancer lesions. AB - One hundred fifteen patients with small (less than or equal to 2 cm in diameter) peripheral lung cancer lesions underwent surgical treatment in the Department of Surgery, The Research Institute for Chest Diseases and Cancer, Tohoku University, Miyagi Prefecture, Japan. The authors investigated several prognostic factors of these cases. The 5-year survival rate of these 115 patients was 70%. Various factors such as histologic type, nodal involvement, pleural involvement, pathologic stage, and curativity of the operation were revealed to affect survival significantly. In patients with and without nodal involvement, there was no significant difference between the survival rate of patients with lung cancer lesions smaller than 2 cm and those with lesions 2.1 to 3 cm. However, the rate of lymph node metastasis was significantly different in the group with lesions smaller than 2 cm compared with those with lesions 2.1 to 3 cm (21% versus 43%, respectively). PMID- 2249207 TI - Choroid plexus tumors in the breast cancer-sarcoma syndrome. AB - Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome. PMID- 2249208 TI - Fallopian tube cancer. The Roswell Park experience. AB - Sixty-four patients with primary fallopian tube cancer treated at Roswell Park Memorial Institute from 1964 to 1987 underwent retrospective clinicopathologic review. In 40 patients fallopian tube cancer was the only primary, but in 24 patients primary fallopian tube cancer was part of a multifocal upper genital tract malignancy. Of the 40 patients with unifocal fallopian disease, the median survival was 28 months. Only 15% of patients were alive and disease free with follow-up ranging from 22 to 141 months (median, 90.5 months). Survival was not associated with stage of disease, tumor histology, grade, or depth of invasion in this series. Fourteen patients who received cisplatin-based chemotherapy were evaluable for response. Three patients (21%) responded; two complete and one partial. Twelve patients without clinical evidence of disease underwent second look procedures, ten laparotomy and two laparoscopy. Four of ten second-look laparotomies were negative. Secondary debulking was done in three of four patients with gross disease, one of which had a negative third-look laparotomy. Negative laparotomy, second-look or third-look, was associated with improved survival (P = 0.016). One of the two laparoscopies was negative, but the patient recurred. In the remaining 24 patients cancer of the fallopian tube was part of a multifocal upper genital tract malignancy. In 12 patients tubal disease was invasive, and in 12, it was in situ. Separate primaries occurred in the ovaries (n = 20); uterus (n = 7); and cervix (n = 2). This represents 1.3% of ovarian malignancies treated at Roswell Park Memorial Institute during the study period. Fallopian tube cancer seems as virulent as ovarian cancer with few long-term survivors. It is frequently associated with other sites of upper genital tract malignancy. Second-look laparotomy is an important predictor of survival. Second look laparoscopy may be useful if positive. PMID- 2249209 TI - True hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, 46,XX/46,XY karyotype, and a successful pregnancy. AB - The first case (to the authors' knowledge) is reported of a true hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, a 46, XX/46,XY karyotype, and a successful pregnancy. The true hermaphroditism was diagnosed during infancy. The patient was subsequently found to have a gonadoblastoma and a microscopic dysgerminoma in the gonad diagnosed as an ovotestis and excised during infancy. The successful pregnancy occurred when the patient was 29 years old. A year later a large gonadal tumor affecting the remaining gonad was excised. The gonad was found to be an ovotestis, and the tumor was a dysgerminoma arising from a gonadoblastoma. This case further emphasizes the malignant potential of the Y chromosome in patients with abnormal gonads. PMID- 2249210 TI - Cancer of the urinary bladder in blacks and whites. A case-control study. AB - Racial differences in the risk of cancer of the urinary bladder associated with cigarette smoking and alcohol consumption were examined in a study of 1663 cases (1534 whites and 129 blacks) and 4930 controls matched 3:1 by sex, race, and age to the cases. Significant increases in cancer risk associated with cigarette smoking were observed in whites and blacks; however, the dose-response patterns appeared to differ by race. In whites, statistically significant elevations of threefold and higher were observed in the odds ratios at all smoking levels above 20 pack-years, whereas in blacks, the corresponding point estimates did not increase significantly until greater than 60 pack-years of smoking. Although these risk patterns are compatible with the higher incidence of bladder cancer in white men, the sample of blacks was small, and tests of significance were only suggestive of higher risks for whites at specific amounts of smoking (P less than 0.15). Effects of alcohol consumption were inconsistent, and there was no detectable synergism between smoking and drinking. Additional study of race specific risk factors and tobacco metabolism will be needed to determine the true nature of the apparent racial differences in the risk of urinary bladder cancer associated with cigarette smoking. PMID- 2249212 TI - Diseases of the pericardium. PMID- 2249211 TI - Diseases of the pericardium. Introduction. PMID- 2249213 TI - Imaging the pericardium. AB - Noninvasive imaging has profoundly altered our ability to diagnose and manage patients with suspected pericardial disease. Although pericardial involvement may first become apparent on a chest radiography, echocardiography (M-mode, 2-D, and Doppler) is the procedure of choice for identifying and characterizing pericardial disease. CT and MRI frequently provide complementary information and in certain instances are necessary for diagnosis. Studies that compare diagnostic accuracy in subsets of patients with pericardial disease are clearly needed, but availability, safety, and cost considerations will influence the choice of procedure. Regardless of the imaging study selected, it is imperative that the results be interpreted in the context of the clinical examination. PMID- 2249214 TI - Pericardial involvement in acute myocardial infarction. AB - The incidence of both early postinfarction pericarditis and post-myocardial infarction (Dressler's syndrome) appears to be declining. Pericardial pain and pericardial friction rub define early postinfarction pericarditis and usually develop on day 2 or 3 after a transmural myocardial infarction. The clinical course is benign, and the prognosis of the patient is not altered by development of this complication. Pericardial effusions have been found in as many as 28% of patients after acute MI. Asymptomatic pericardial effusions do not require specific therapy nor do they absolutely contraindicate the use of anticoagulation as was previously thought. The preferred form of therapy for early postinfarction pericarditis is aspirin. Avoidance of corticosteroids and NSAIDs must be considered carefully because of the reported complications of these agents. The post-myocardial infarction syndrome develops usually during the second or third week after acute MI but may be seen as early as 24 hours and as late as several months after the MI. Whether this syndrome is the result of autosensitization to myocardial antigens released into the circulation during infarction remains uncertain. Alternative hypotheses for the causation of the syndrome include the release of blood in the pericardial space and simply that the syndrome represents a prolonged and exaggerated form of early postinfarction pericarditis. Clinically, post-myocardial infarction syndrome is manifested by fever, malaise, chest pain, and the presence of a pericardial and possibly pleuropericardial friction rub. Pericardial effusion is frequently large, and, rarely, cardiac tamponade may develop and require pericardiocentesis. Treatment consists of aspirin, NSAIDs, or corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249215 TI - A systematic diagnostic approach to primary acute pericardial disease. The Barcelona experience. AB - Acute pericarditis and cardiac tamponade without a definite cause at the time of the initial hospital evaluation are defined as primary acute pericardial disease. In immunologically competent patients from the Western World, most cases (more than 80%) are idiopathic. However, severe specific diseases may be present in the remaining cases, the clinical features often providing insufficient clues to the etiologic diagnosis. A systematic approach to these patients is therefore needed. It is relevant to this approach that pericardiocentesis and pericardial biopsy have a much higher diagnostic yield when performed in patients with cardiac tamponade than when they are performed for purely diagnostic purposes. Strategies to increase this yield might be devised on the basis of noninvasive findings. PMID- 2249216 TI - Recurrent pericarditis. AB - The most common background for recurrent pericarditis is that of acute nonspecific pericarditis. Relapsing pericarditis also may follow cardiac trauma, cardiac operations, myocardial infarction, and intrapericardial bleeding. The exact recurrence rate after initial attacks of idiopathic pericarditis is unknown but appears to be in the range of 15% to 32%. The mechanism of recurrent pericarditis is uncertain. An autoimmune response has been proposed, but this concept is unproved. Yoneda and coworkers, in a case of pericarditis due to coxsackie B virus, found no rise in antibody titer to this virus during recurrences. The prognosis, except for disabling pain and malaise, is good, and constrictive pericarditis, chronic myocardial disease, and cardiac tamponade are unusual complications. Although constrictive pericarditis may follow an initial attack of idiopathic pericarditis, it was reported in neither two other series of patients with relapsing pericarditis nor in this series. Cardiac tamponade has been reported as an occasional complication of relapses but did not occur in our patients. None of our patients died. Most patients with recurrent pericarditis respond to adrenal steroid therapy, but many times there is difficulty in weaning the patient from the drug. Because it is suspected that adrenal steroids may prolong attacks and promote tendency to further recurrences, initial therapy should be offered with aspirin or NSAIDs, and adrenal steroid therapy should be used only when there is no response to these agents. Recurrences may take place over a period lasting as long as 15 years, and patients with as many as 19 recurrences have been described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249218 TI - Acute pericarditis. AB - Acute pericarditis may be of viral or idiopathic origin, may be induced by certain drugs, may occur as a consequence of thoracic surgery, may result from infection by bacteria or other organisms, or may be associated with noninfectious systemic disease. In some instances, pericarditis may be detected quickly, and in other cases it may not be recognized until late. This article discusses clinical findings, clinical course, and treatment of acute pericarditis. In addition, diagnosis and treatment of pericardial effusion are presented. PMID- 2249217 TI - Cardiac tamponade. AB - Hemodynamic abnormalities induced by pericardial effusion can be categorized by stages. During phase I, pericardial and left and right ventricular pressures are elevated but not equilibrated, and cardiac output is not compromised. During phase II, elevated pericardial and right ventricular filling pressures are equilibrated with each other but not with left ventricular filling pressure, which is higher. Cardiac output is compromised, and pulsus paradoxus is present in most but not all patients. During phase III, elevated pericardial right ventricular and left ventricular filling pressures are equilibrated, cardiac output is severely compromised, and pulsus paradoxus is present in all patients. PMID- 2249219 TI - Constrictive pericarditis. AB - Constrictive pericarditis is a complex disorder characterized by abnormal thickening of the pericardium that leads to pathologic changes in cardiac hemodynamic data. The disorder can be suspected by history and physical findings. Data from echocardiography, CT, and MRI offer diagnostic information. The diagnosis cannot generally be established with certainty by noninvasive methods. Additional information from cardiac catheterization may help confirm the diagnosis. Together, these diagnostic modalities aid in the assessment of disease and help to differentiate it from related conditions such as restriction, cardiac tamponade, and right ventricular infarction. Treatment is largely surgical, and new techniques and approaches have made it relatively safe. Early diagnosis and pericardiectomy may lead to cure in most patients. PMID- 2249220 TI - The differentiation of restrictive cardiomyopathy from constrictive pericarditis. AB - The differentiation of restrictive cardiomyopathy from pericardial constriction remains a difficult clinical problem. Although the historical, noninvasive, and hemodynamic and angiographic features discussed here provide poor discriminating value when considered individually, a combination of clues may suggest one diagnosis or the other. Endomyocardial biopsy affords the greatest hope of avoiding unnecessary surgical exploration. Thoracotomy continues, however, to be the gold standard by which to make the distinction, carrying with it significant risk in patients with underlying restrictive cardiomyopathy. PMID- 2249221 TI - Neoplastic pericardial disease. AB - The spread of metastatic cancer to the pericardium is the most common cause of cardiac tamponade in medical inpatient settings. Lung cancer, breast cancer, and the hematologic malignancies account for some three quarters of the cases. Occasionally, usually in lung cancer, the pericardial involvement is the first clinical presentation of the neoplastic disease. Differential diagnosis includes radiation pericarditis and cardiac toxicity from chemotherapeutic drugs, as well as any of the causes of pericardial disease in patients without neoplasm. Idiopathic nonneoplastic, noninflammatory pericardial effusion is surprisingly common in cancer patients. The initial cardiac tamponade may be managed with either needle tap or subxiphoid pericardiostomy. Pericardiocentesis, performed with echocardiographic guidance and followed by percutaneous catheter drainage for several days, is safe and effective in neoplastic pericardial effusion. It may be the only local therapy that is needed. Further local treatment, for those patients who develop recurrent cardiac tamponade after an initial drainage procedure, may include tetracycline sclerosis of the pericardial space, instillation of cancer chemotherapeutic agents, radiation therapy, and pericardiectomy. No controlled clinical trials of these methods of treatment are available. The choice of therapy is based on various considerations in individual patients, particularly the patient's general condition and the likelihood of a long-term response to treatment of the systemic neoplastic disease. PMID- 2249222 TI - Surgical management of pericardial diseases. AB - The institutional experience of the Mayo Clinic in the surgical management of pericardial disease is reviewed. The historical background, indications for, and results of surgical therapy are presented in the management of constrictive pericarditis, effusive pericardial diseases, and recurrent (relapsing) acute pericarditis. With current operative techniques and perioperative management, the vast majority of patients with these conditions can be operated on safely and expect long-term relief of symptoms, with improvement in functional class and survival. PMID- 2249223 TI - Pericarditis in AIDS. AB - A wide variety of organisms and conditions have been reported to cause pericarditis in patients that present and die with AIDS. Although pericarditis is remarkably common in patients dying of AIDS, no consistent pattern of cause emerges. Patients with AIDS are susceptible to pericarditis as a concomitant of the terminal condition, but it seldom contributes to the patient's death. Alternatively, pericarditis (as opposed to silent pericardial effusion) as a cardinal symptom in a patient's illness is likely to have an origin that can be ascribed to organisms typically associated with infectious pericarditis in those patients who have profound cellular immunodeficiency. Thus, it is important to make the diagnosis of infectious or neoplastic pericarditis in the setting of AIDS, since control of the agent has the potential of influencing the clinical course. In the absence of signs of hemodynamic compromise or inflammation, pericardial effusion may be accepted as an accompaniment of pleural effusions or ascites in the appropriate clinical context. Invasive diagnostic measures may be reserved for those cases in which pericardial disease is a prominent feature of the symptom complex or of accompanying pleural effusion. The study of epidemiology and biology of AIDS is a rapidly changing field. Explanations of the high incidence of pericardial disease in terminal disease may emerge with broad ranging studies of the incidence of myocarditis in AIDS as well as the relative contribution to pericardial disease of agents used in the treatment of the illness. PMID- 2249224 TI - Pericarditis in end-stage renal disease. AB - Our approach to the clinical management of uremic and dialysis-associated pericarditis has been presented previously and is outlined in Figure 1. In hemodynamically stable patients with no effusion and in those with small to medium effusions, we recommend initial therapy with intensified dialysis. Close monitoring, perhaps every third day, with echocardiography should be carried out. If pericardial effusion progressively increases or if a large pericardial effusion fails to resolve after 7 to 10 days of intensive dialysis, the pericardial effusion may be drained by subxiphoid pericardiotomy or by pericardiectomy. Similarly, if hemodynamic evidence of cardiac pretamponade or tamponade appears, surgical drainage also should be carried out. If the echocardiogram is inadequate for interpretation but tamponade physiology is present, we recommend confirmation by cardiac catheterization before surgical drainage is attempted, recognizing that there may be circumstances such as left ventricular failure and pulmonary hypertension that may complicate the interpretation of the catheterization data. The type of invasive pericardial procedure chosen is determined by local experience. As stated, we prefer not to perform pericardiocentesis before surgery unless tamponade-induced hypotension is so severe that an adequate blood pressure cannot be maintained by means of plasma volume expansion. Under these circumstances, we prefer that pericardiocentesis be performed in the operating room immediately before the induction of anesthesia for the definitive surgical procedure. Although pericardiectomy is a definitive procedure for pericarditis with effusion in the uremic patient, the procedure has substantial morbidity. The results of subxiphoid pericardiotomy are encouraging, and it is clear that it can be carried out safely in patients who are debilitated or who are at increased risk from general anesthesia and major surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249225 TI - Pericarditis in systemic diseases. AB - Acute pericarditis is associated with four categories of systemic diseases: vasculitis-connective tissue disease; immunopathies and hypersensitivity states; disorders of metabolism; and diseases of uncertain origin or in association with various syndromes. Multiple overlapping may occur among these categories. This article discusses clinical signs and treatment of pericarditis as it occurs with these diseases. PMID- 2249226 TI - Behavioural aspects of dietary habits and dental caries. PMID- 2249227 TI - Changes in the prevalence of dental caries: how much can be attributed to changes in diet? PMID- 2249228 TI - Diet and caries in high-risk groups in developed and developing countries. PMID- 2249229 TI - Food composition and food cariogenicity factors affecting the cariogenic potential of foods. PMID- 2249230 TI - [Changes in NK cell activity in patients with acute leukemia]. AB - Examination of the activity of NK-cells in peripheral mononuclear cells (PMNB) of patients with acute leukaemia (AL) was implemented before the onset of treatment and in the course of the disease following cytostatic treatment. The examination was made by the isotope method based on the release of 51Cr after 4-hour cultivation of effector cells with target cells of line K 562. The mean percentage of NK cellular activity in patients with AL was 9.9 and 5.9, as compared with normal values of 56 and 41 with ratios of effector and target cells of 40:1 and 20:1. The course of the disease after cytostatic treatment revealed that patients where complete remission occurred had before onset of treatment on average a higher NK-cell activity than those who responded poorly to treatment. In the majority of patients who were in complete remission the activity of NK cells increased markedly. PMID- 2249231 TI - [Monoclonal antibodies against fibrinogen and fibrin and against their proteolytic degradation products]. AB - The level of fibrinogen (FDP) and fibrin (fDP) degradation products is one of the surprisingly few unequivocal indicators of the activity of the coagulation and fibrino (geno) lytic system. Today it is beyond doubt that, similarly as the FDP/fDP level is of unequivocal importance, traditional methods of their assessment are very equivocal. Fibrin and FDP/fDP are molecules derived from fibrinogen, which are formed from the latter as a result of a series of reactions during which structures are formed or are made available which are not present in the fibrinogen molecule. New antigenic determinants are formed, in relation to the original molecule so-called neoepitopes, neoantigens. The great predominance of monoclonal antibodies prepared in the meantime reacts with fibrinogen as well as with fibrin and their degradation products. By means of specific approaches and original methods it proved, however, possible to prepare some specific monoclonal antibodies which were successfully used in diagnostic tests in vitro; their use for detection of thrombi in vivo is tested as well as their use for an increasingly effective thrombolytic therapy after their conjugation with plasminogen activators. It may be expected that this problem will be intensely developed in the near future. PMID- 2249232 TI - [Personal experience with treatment of acute myeloid leukemia using the DAT combination]. AB - A combination of cytostatics--Rubomycin (Medexport), Alcysten (Spofa) and LANVIS (Wellcome) was used to treat 44 patients with the diagnosis AML. A total of 66% CR was achieved. The median duration of CR was 15 months and the median of survival of patients with CR was 25 months. 20% of the patients died in induction mostly from infectious complications. The authors assume that this combination with the use of the Czech preparation Alcysten and the Soviet preparation Rubomycin is suitable induction treatment in AML. Treatment, however, calls for perfect supporting therapy and therefore should by concentrated in selected departments. PMID- 2249233 TI - [The importance of determination of ferritin levels in erythrocytes]. AB - The basic ferritin level in red cells was examined in 60 healthy volunteers and in 110 patients with various diseases of the red cell series. From samples of heparinized whole blood first leucocytes were removed and then they were haemolyzed. After subsequent centrifuging in the supernatant the basic ferritin content was assessed by means of an Amersham Ferritin RIA kit (Amersham, Great Britain). Normal values in healthy volunteers varied between 3.2 and 30.2 ag/ery. In patients with iron deficiency the values were significantly reduced, in patients with pernicious anaemia, beta-thalassemia minor, hereditary spherocytosis and glucose-6-phosphate dehydrogenase deficiency or pyruvate kinase deficiency the levels of red cell ferritin were significantly elevated, as compared with the control group. The red cell ferritin level depends on the iron supply to cells of the red cell series and the amount needed for erythropoiesis. A reduced supply in sideropenia leads to a reduced level of red cell ferritin, in haemolytic anaemia its level depends on the generally elevated iron supply in the organism and possibly impaired haemoglobin synthesis, on the one hand, and concurrent elevated iron requirements in case of hyperplasia of red cell formation, on the other hand. Assessment of red cell ferritin is important not only for accurate estimation of the amount of iron available in the cell for haeme formation but also to elucidate the pathogenesis of some changes of iron metabolism in diseases of the red cell series. PMID- 2249234 TI - [The importance of prognostic signs in malignant diseases]. AB - The paper deals with the general importance of prognostic signs in malignant tumours. The author defines basic terms such as disease, illness, sign etc. Diagrams describe individual stages and the complexity of the diagnostic and therapeutic procedure and the main factors which influence its result, the patient's recovery. From the aspect of assessment of the accurate diagnosis signs assembled during the diagnostic process are divided into three prognostic groups as the correct diagnosis is the prerequisite of rational therapy and thus can influence the prognosis of the disease. In the first group are only signs associated with the aetiopathogenesis of the disease, in the second group signs associated with the patient's general condition and in the third group signs of the patient's normal phenotype. The signs in each of these groups have as a rule a different prognostic value. The author emphasizes the great dependence of prognostic signs on the type of applied treatment as well as the fact that with improving treatment the majority of signs lose their prognostic importance. PMID- 2249235 TI - [Use of flow cytometry in the determination of HLA antigens]. AB - The authors compare the classical method of typing of HLA antigens by the microlymphocytotoxic test (CTX) and the results obtained by flow cytometry (FCTX). They investigated agreement of results as regards estimation of 14 HLA antigens, loci A and B. in 42 sera. They compared possibilities of flow cytometry using microquantities of material and investigated changes of results obtained by cytotoxic reactions after 24 hours. The results evaluated by linear regression analysis proved the comparability of flow cytometry and the classical microlymphocytotoxic test. PMID- 2249236 TI - [The patrons of physicians, Cosmos and Damian, in Czech art]. PMID- 2249237 TI - [The transfer of pesticidal agents in the agricultural ecosystem]. AB - The author gives and account of the most important pesticides with regard to the purpose they are used for in agricultural production, their development in the world and in Czechoslovakia, methods of their application and toxicological aspects. Attention is drawn in particular to the main groups of pesticides and their content in foods (milk, fish, free living animals etc.). The way suggested for the solution of this problem is integrated biological protection of plants. PMID- 2249238 TI - [The effect of a combined transplantation of the pancreas and kidney on the course of peripheral diabetic neuropathy]. AB - Sixteen type I diabetics were followed up from the neurological aspect and by electromyography for 6 to 42 months following successful combined transplantation of the pancreas and kidney. Before transplantation all patients suffered from medium severe to severe peripheral polyneuropathy, grade 3-5 according to the commonly used quantitative classification. All patients reported after transplantation subjective improvement, e.g. of the muscular strength or steadiness of gait. In six patients the clinical and in eight patients the electromyographic finding improved by one grade, in four patients at least the conductivity in the nerves of the upper extremities improved. In four patients the neurological and electromyographic finding did not change; none of the patients after successful transplantation deteriorated. The authors discuss the favourable effect not only of elimination of the uraemic syndrome, but also the effect of the improved carbohydrate metabolism on regenerating processes in the peripheral nervous system. PMID- 2249239 TI - [The effect of the duration of a weight reduction regimen on the hormonal, metabolic and cardiovascular response]. AB - The rapid weight decrease at the beginning of strict slimming regimens leads often to an inconsiderate shortening of these cures. Our long-termed experience with a slimming regimen lasting 13 days and based on diet (3.7 MJ) and 4 hours of supervised exercise of low to moderate intensity was omitted by the organizers. They shortened the cure to 8 days. We checked therefore a group of obese women on the first, eighth and twelfth day in the course of this regimen. A statistically significant decrease of serum insulin, growth hormone, triiodothyronine and cholesterol was observed on the twelfth day. These trends were not significant on the eighth day. On the other hand, the step-test has shown on the eighth day a reduction of the heart rate during recovery. Nevertheless, a higher level of significance was obtained after a cure of 12 days. No significant response to the regimen was obtained in the case of blood glucose, thyroxine, cortisol, uric acid, AST and ALT. The advantages of the 12 day regimen were discussed- especially the decrease of insulinemia, because hyperinsulinemia is responsible for several complications of obesity. The importance of the decrease of cholesterolemia and the modification of heart rate after a load was also stressed. These favourable effects should not be depreciated by a smaller weight decrease on the second week due to an enhanced synthesis of proteins, stimulated by exercise and supported by a decrease of T3 which brings a protection against energy defficiency. PMID- 2249240 TI - [The causality of lunar changes on cardiovascular mortality]. AB - The author confirmed, based on different ways of processing of 1437 sudden cardiovascular deaths, that the frequency of these deaths changes in the course of the synodic moon with two maxima during the lunar quarters. Processing by the method of transfer of epochs made it possible to shift steadily the mortality curves according to the phase of solar activity. This made the author assume that the cause of the phenomenon of two-phasic change of mortality during lunation cannot be only gravitation (sudden tides) and that in addition the interfering influence of solar corpuscular radiation is involved. It is known that this radiation causes geomagnetic disorders. Consistent with the above view it was proved that in the course of lunation the greatest number of geomagnetic disorders occur at a time close to the lunar quarters. Then, as the author proved -aurora polaris is more frequent. The increased cardiovascular mortality is thus associated with an increased geomagnetic activity. The relationship is certainly not direct. The author indicates further trends of research to disclose the immediate causes which exert an unfavourable effect on our cardiovascular system. PMID- 2249242 TI - [Memories of professor Rudolf Eiselt and the Clinic for Diseases of the Aged]. PMID- 2249241 TI - [Preclinical modeling of the possible effect of acute uremia on drug resorption in the gastrointestinal tract]. AB - The authors investigated in experiments on rats the course of serum concentrations of sulfisoxazole (S) and acetylsulfisoxazole (AS) in normal rats and in rats after bilateral nephrectomy after intra gastric administration of S. Serum concentrations of S and AS during the first three hours following administration did not differ significantly or were very close. During the subsequent hours the serum concentrations of S and AS in uraemic animals were significantly higher than in controls. The value of the absorption constant in the uraemic animals was on average higher and the absorption half-life lower than in controls. The assembled results suggest that in acute uraemia in rats the intestinal reabsorption of S and its metabolism in the liver are not reduced. The findings support the idea that the model used could be useful in preclinical research of drugs used in the treatment of acute uraemia. PMID- 2249243 TI - [A specific geriatric regimen. I]. AB - The authors discuss the characteristic and justification of a specific geriatric regime, or geriatric departments, and give an account of their experience assembled in tests of this regime under conditions of the geriatric centre of the Third Medical Clinic, Prague, in particular with regard to the general orientation as regards hospitalization of geriatric patients. PMID- 2249244 TI - [A specific geriatric regimen. II]. AB - The authors discuss individual nursing components of the specific geriatric regime. Attention is paid to problems of activation of geriatric patients, cooperation with their families, the system of controlled visits, an individual approach focused on comprehensive solution of the situation in life. Special attention is paid to rationalization of the diagnostic and therapeutic programme with an effort to reduce the administration of tranquillizers. PMID- 2249245 TI - [Change from treatment with cyclosporin A to conventional treatment in kidney transplantation]. AB - Patients after a first transplantation of the kidney from a dead donor treated with cyclosporin A in combination with one, two or three drugs were switched to conventional treatment with azathioprine and prednisone. Fifty-two patients were switched to the new treatment 11-15 months after transplantation (group I), 9 patients after 6-10 months (groups II), 17 patients after 16-30 months (groups III). Group I was compared with 21 patients where no switched was made after 11 15 months (group IV). The authors did not reveal any change in the survival of grafts nor in the number of rejections during the three-month period following the switch. Survival of grafts in patients with rejection was after two years following the switch significantly lower than in patients without rejection, the loss of grafts, however, did not differ as compared with patients who suffered a rejection during a comparable period but were not switched to conventional therapy. The interval of the switch after transplantation did not influence the incidence of rejections. Rejections after the switch cannot be reliably foreseen from the level of cytotoxic anti-HLA antibodies or previous repections before the switch. PMID- 2249246 TI - [Midline granuloma]. AB - Midline malignant granuloma is the term used for a histogenetically heterogeneous group of diseases characterized by progressing destruction of tissues of the sinonasal area. The difficulty of differentiation of basic clinical pathological units included in this group, which is of fundamental importance for the subsequent therapeutic procedure, is demonstrated on two cases of Wegener's granulomatosis and sinonasal pleomorphous reticulosis. PMID- 2249247 TI - [Physician-martyrs of the Czech resistance during World War II. III]. PMID- 2249248 TI - Role of the CDC8 gene in the repair of single strand breaks in DNA of the yeast Saccharomyces cerevisiae. AB - It has been found that the repair of single strand breaks is defective in the DNA replication mutants cdc8-1 and cdc8-3 of Saccharomyces cerevisiae both in permissive (23 degrees C) and restrictive conditions (36 degrees C). In permissive conditions we observed a significant delay in single strand break repair in a diploid strain HB7 (cdc8-1/cdc8-1), as compared with the wild-type strain. Under restrictive conditions no repair was observed, but rather degradation of MMS-damaged DNA occurred. It has been also found that the repair of single strand breaks in yeast is inhibited by cycloheximide but not by hydroxyurea. PMID- 2249249 TI - Resistance to cadmium is under control of the CAD2 gene in the yeast Saccharomyces cerevisiae. AB - A cadmium-resistant strain, X3382-3A, which is able to grow in a medium containing 0.2 mM cadmium sulfate, was picked out from our laboratory stock strains of Saccharomyces cerevisiae. The cadmium resistance of this strain is controlled by a single dominant nuclear gene, denoted as CAD2. The locus of CAD2 was mapped by gene linkage to a site 15.5 centimorgans to the right of the his7 locus on the right arm of chromosome II. The cadmium resistance of the strain carrying CAD2 was evaluated for its properties of cadmium uptake, cadmium distribution and cadmium-metallothionein formation, in comparison with those of some other strains. The results suggest that the novel type of cadmium resistance controlled by CAD2 does ot involve production of a cadmium-metallothionein. PMID- 2249250 TI - A recessive mutant allele of the HNM1 gene of Saccharomyces cerevisiae is responsible for hyper-resistance to nitrogen mustard. AB - A screening of haploid yeast strains for enhanced resistance to nitrogen mustard (HN2) yielded a recessive mutant allele, hnm1, that conferred hyper-resistance (HYR) to HN2. Diploids, homo- or heterozygous for the HNM1 locus, exhibit normal wild-type like resistance while homozygosity for hnm1 leads to the phenotype HYR to HN2. The hnm1 mutation could be found in yeast strains proficient or deficient in different DNA repair systems. In these mostly HN2-sensitive haploid repair deficient mutants, hnm1 acted as a partial suppressor of HN2 sensitivity. All isolated recessive mutations conferring hyper-resistance belonged to a single complementation group. The HYR to HN2 phenotype was maximally expressed in growing cells and was associated with reduced mutability by HN2. HNM1 most probably controls uptake of HN2 which would be impaired in the hnm1 mutants. PMID- 2249251 TI - The recombinational hot spot mutation ade6-M26 of Schizosaccharomyces pombe stimulates recombination at sites in a nearby interval. AB - With the help of in vitro constructed intragenic double mutants, we investigated the influence of the recombinational hot spot mutation ade6-M26 on meiotic recombination between two additional ade6 mutations proximal to it. Recombination was stimulated four-fold when M26 was present in a heterozygous condition and ten fold when homozygous. M26 itself remained unaffected in a substantial number of these events. This indicates that the stimulation can not only be due to a preferred conversion of M26 to wild-type with co-conversion of the second mutation in cis. A model is proposed in which M26 acts as an "entry site" for recombinational enzymes. PMID- 2249252 TI - Detection of length heterogeneity in the ribosomal DNA of Pythium ultimum by PCR amplification of the intergenic region. AB - About one-half of the ribosomal repeat unit of two isolates of Pythium ultimum was amplified by means of the polymerase chain reaction using one primer pair. The amplified region includes a small part of the large subunit ribosomal RNA gene, about half of the small subunit ribosomal RNA gene, and the entire intergenic region. The intergenic region of both isolates of P. ultimum has length heterogeneity due to the presence of subrepeat arrays (Klassen and Buchko 1990). PCR amplification of the heterogeneous target DNA resulted in sets of fragments which accurately reflect the heterogeneity in the target DNA, although there is a preferential amplification of the smaller targets. PCR product sizes ranged from 4.6 to 5.8 kb. PMID- 2249253 TI - Cloning and sequence analysis of a cDNA for cellulase (FI-CMCase) from Aspergillus aculeatus. AB - We have cloned and characterized the cDNA coding for a major component of cellulase, endoglucanase (FI-CMCase), produced by Aspergillus aculeatus. The cDNA was isolated from a A. aculeatus cDNA library using synthetic oligonucleotide mixtures that correspond to the internal amino acid sequence of the mature FI CMCase protein. Nucleotide sequence analysis of the cloned cDNA insert revealed a 711 bp open reading frame that encoded a protein of 237 amino acid residues. The primary structure of FI-CMCase deduced from the nucleotide sequence of cDNA agreed with that found by amino acid sequencing of peptide fragments obtained by digestion with several proteinases and cyanogen bromide cleavage. There may be a signal peptide sequence of 16 amino acid residues at the N-terminus. The molecular mass of the mature protein calculated from the cDNA is 24002 daltons, which compares favorably with molecular mass estimates of purified FI-CMCase obtained from SDS-PAGE (25000 Da). No distinct homology was found between the amino acid sequence of FI-CMCase and known cellulase sequences of other microorganisms. This study is the first example of cDNA cloning of an endoglucanase from the genus Aspergillus. PMID- 2249254 TI - The ndhH genes of gramminean plastomes are linked with the junctions between small single copy and inverted repeat regions. AB - The junctions JSA and JSB between the two inverted repeat regions IRA and IRB and the small single copy region of the maize chloroplast DNA have been identified by DNA sequencing. The JSA junction coincides with the initiation codon of the ndhH gene which is encoded by the adjacent region of the small single copy region. A comparison with the plastomes of rice, rye, tobacco and liverwort shows that linkage of this junction with the ndhH gene is specific for gramminean species. The amino acid sequences deduced from the ndhH genes show conserved histidine and cysteine residues which are likely to form a metal-binding domain. PMID- 2249255 TI - Detection of chloroplast DNA by using fluorescent monoclonal anti bromodeoxyuridine antibody and analysis of its fate during zygote formation in Chlamydomonas reinhardtii. AB - A monoclonal anti-bromodeoxyuridine antibody conjugated to fluorescein was used to detect the chloroplast nucleoids after specific incorporation of bromodeoxyuridine (BUdR) into the chloroplast DNA of Chlamydomonas reinhardtii. The incorporation of BUdR was enhanced by simultaneous treatment with fluorodeoxyuridine (FUdR). The method was applied to analyze the fate of chloroplast DNA in zygotes resulting from mating between BUdR-treated gametes (mt+ or mt-) and untreated gametes of opposite mating-type. In crosses between wild-type strains, the nucleoids of mt+ origin remained in the large majority of zygotes whereas those of mt- origin most often disappeared within the first hours following copulation. In crosses of the type mat-3 mt+ x wild-type mt- (the mat-3 mutation permits a high transmission of chloroplast genes from the mt- parent), the nucleoids of mt- origin were generally not eliminated which indicates that the mat-3 mutation prevents the selective destruction of paternal chloroplast DNA in the zygote. PMID- 2249256 TI - Flow cytometry as a tool to discriminate respiratory-competent and respiratory deficient yeast cells. AB - The cationic lipophilic dye Rhodamine 123 (Rh123) is selectively enriched in mitochondria in a membrane potential-dependent manner. Application of drugs which interfere with the electron flow of the respiratory chain lead to a severe reduction of mitochondrial dye uptake. In this communication we show that the same effect is observed after Rh123-staining of respiratory-deficient yeast mutants. Based on this observation we used flow cytometry to discriminate respiratory-competent and respiratory-deficient yeast cells. Combined with a cell sorter we were able to selectively enrich respiring and non-respiring yeast cells, respectively, from a mixture of cells. PMID- 2249257 TI - The structural gene coding for thiamin-repressible acid phosphatase in Schizosaccharomyces pombe. AB - The pho4 gene of the fission yeast Schizosaccharomyces pombe is regulated by thiamin. The nucleotide sequence of this gene is given here and it is shown that it matches the amino acid sequence of thiamin-repressible acid phosphatase, corroborating genetic evidence that pho4 represents the structural gene of this enzyme. The gene codes for a protein of 463 amino acids in length and shows regions of strong similarity with the phosphate-repressible acid phosphatase of Schizosaccharomyces pombe. The enzyme has a cleavable signal sequence 18 amino acids long and carries nine potential N-glycosylation sites. PMID- 2249258 TI - Restriction site and genetic map of Cucurbita pepo chloroplast DNA. AB - A detailed restriction map of squash chloroplast DNA (cpDNA) was constructed with five restriction endonucleases, SalI, PvuII, BglI, SacII, and PstI. The cleavage sites were mapped by sequential digestion of cpDNA using low-gelling temperature agarose. The restriction map shows that squash cpDNA is an approximately 153 kilobase (kb) circle with a large inverted repeat sequence of 23.3 kb, separated by a large (83.7 kb) and a small (22.7 kb) single copy region. Genes for a number of chloroplast polypeptides were localized on the map by hybridizing the cpDNA restriction fragments to heterologous gene-specific probes from tobacco, pea, tomato, maize, and spinach chloroplasts. The gene locations and organization of squash cpDNA are highly conserved and similar to chloroplast genomes of tomato, pepper, and Ginkgo. PMID- 2249259 TI - Organization of ribosomal DNA in the basidiomycete Thanatephorus praticola. PMID- 2249260 TI - [Retinopathy of prematurity over 3 decades]. AB - The authors give an account of 190 premature infants they treated in 1956-1988, suffering from retinopathy of prematurity--ROP, and for prolonged subsequent periods. As the head of the team followed up all the children, there is an integrated view of the problem. The birth weight of the infants was 640 g--1,900 g. From the total number 76.8% infants had a birth weight of 1,500 g or less, 13.7% had a birthweight of 1,000 g or less. Evidence of the increasing rate is provided by the number of patients treated since birth at the department for premature and pathological infants FNM as well as by the number of children admitted from other departments after development of ROP. In 1956-1970, i. e. in 15 years, the authors looked after 34 patients, in 1971-1988, i. e. in 18 years there were 156 children with ROP. In 1956-70 cases of ROP predominated which developed as a result of absolute or relative hypoxia. They were successfully treated by individually adjusted and carefully controlled oxygen therapy (6.9% blind children). In 1971-1975 the possibility to use this therapy declined briskly because after introduction of modern medical technique the number of findings suggesting a hyperoxic insult increased. At that time the results deteriorated greatly (50% blind children). In 1976-1980 the results were favourably influenced by individual dosage of oxygen therapy in all infants, based on regular monitoring of blood gases (10.5% blind children).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249261 TI - [Secondary implantation of intraocular lenses]. AB - In 17 eyes of 16 patients a secondary lens implantation was performed. In 10 eyes with intact posterior lens capsule a retropupillar (PC) lens was implanted, in the other 7 a AC lens. The VA was always good, in two eyes a secondary glaucoma was found, in one it was transient, in the other a LTP was performed. In one eye a decentration for posterior synechiae arose. PMID- 2249263 TI - [The effect of general anesthesia on the position of the eye]. AB - In 100 children operated on account of strabismus the authors tried to assess whether changes in the position of the eyeballs during general anaesthesia with the stretch test can contribute towards the decision on the magnitude of the surgical operation. At the same time they compared changes in the position of the eyeballs during intubation anaesthesia by means of nitrous oxide and halothane with anaesthesia with ketamine, administered by the i.m. or i.v. route. They found that in 92% of the examined subjects the position of the eyeballs changed during general anaesthesia, most frequently the convergent deviation diminished. During ketamine anaesthesia the changes were more marked. The stretch test was in 73% of the patients normal, in 93% it was equal in both eyes. Based on the results, the authors conclude that neither the evaluation of changes of the eyeballs during general anaesthesia nor the stretch test can make the dosage of the surgical operation in concomitant strabismus more accurate. PMID- 2249262 TI - [Long-term results after implantation of silicone orbital implants]. AB - In 1980-1988 at the Second Ophthalmological Clinic 78 enucleations of the bulbs with a orbital silicon implant were performed. The tolerance of the implant and the cosmetic result of the operation was evaluated in 53 adults and 5 children. The observation period varied between 6 months and 7 years. From the total number of 53 adults a very good cosmetic effect was achieved in 9 (17.1%), a good effect in 25 (47.1%), a satisfactory effect in 12 (22.6%) a poor effect in 2 (1.8%) patients. The implant was rejected in 5 (9.4%) of the cases, 4 implants within one month and one two years after enucleation. A very good cosmetic effect was observed in one (20%) child and a good effect also in one (20%). The implant was rejected in 3 (60%) children, 1, 4 and 20 months after operation. Rejection after 20 months was preceded by an inflammatory reaction in the area of the implant. Rejection of orbital silicon implants in adults was as a rule due to surgical complications or incorrect surgical technique. In the rejection of implants in young children the increased biological reaction of the child organism may be involved. PMID- 2249264 TI - [A rare case of corneal abscess caused by Wangiella dermatitidis]. PMID- 2249265 TI - [The floppy eyelid syndrome]. AB - The floppy eyelid syndrome is a disease characterized by chronic papillary conjunctivitis which practically does not respond to common local treatment. Obese men are most frequently affected. The cause is degeneration of collagenous connective tissue which causes an abnormal consistency of the tarsus, floppy eyelids, in particular the upper ones and thus during sleep eversion of the eyelids occurs with subsequent drying up and mechanical irritation of the mucosa. The complaints are most severe closely after awakening. Improvement is achieved by mechanical protection of the eyelids during sleep. Surgical treatment of the eyelids would be a permanent solution. PMID- 2249266 TI - [Cryotherapy in the treatment of retinopathy of premature neonates]. AB - The author gives a brief account on the use of cryodestruction of the peripheral retina to prevent the development of irreversible stages of retinopathy of the newborn. The author defines the suitable time of indications, describes the technical procedure, complications and subsequent possible treatment. The method is supplemented by the author's results obtained in a group of patients. PMID- 2249267 TI - [Retinopathy of prematurity--ophthalmologic care at units for premature infants in type I and II hospitals]. AB - The author assessed by means of questionnaires organizational aspects of ophthalmological care of premature infants in departments for premature infants in type I and II hospitals. He discusses therapeutic possibilities of children with developing retinopathies of the premature in these departments. In the conclusion he emphasizes that from the organizational aspect consultant services at this level are ensured in a satisfactory way. The actual professional standard cannot be evaluated from questionnaires. PMID- 2249268 TI - [Excimer lasers in ophthalmology. Review]. PMID- 2249269 TI - [Disinfection of ophthalmologic tonometers]. AB - The authors describe an automatic instrument of their own design for disinfection of ophthalmological tonometers by germicide radiation. The tests of effectiveness against microbes (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa), spores of Bacillus mesentericus, adenoviruses and viruses of Herpes simplex provided evidence of a high disinfectant potency of the apparatus. PMID- 2249270 TI - [Clinical contribution of the examination of immunoglobulins and albumin in the feces in children (a group of 610 patients 1-18 years of age]. AB - The authors submit their experience with the examination of immunoglobulins and albumin in the faeces of patients with different diseases of the gastrointestinal tract. The presence of antibodies IgA, sIgA, IgM and albumin were assessed in lavages from the rectum or supernatant of the faeces, using the qualitative method of double immunodifussion according to Ouchterlony. A normal finding is characterized by the presence of IgA, sIgA. For evaluation of the clinical importance and applicability of the examination method the authors draw attention to the importance of asessing the degree of positive or negative correlation between findings and the final diagnosis. The authors present three basic pictures; acute inflammation, chronic inflammation, non-inflammatory exsudation (exsudative enteropathy). They analyze the clinical application of different findings and their practical impact. They give an account of limiting factors in the evaluation of the presence of immunoglobulins and albumin in faeces. PMID- 2249271 TI - [Hepatobiliary gammagraphy in the diagnosis of Dubin-Johnson syndrome in children]. AB - Using hepatobiliary gammagraphy (99mTc-EHIDA), the authors made 26 examinations in six families with Dubin-Johnson's syndrome. From a series of gammagrams they evaluated the hepatobiliary kinetics and from measurements of the activity of series of blood samples they assessed the half-time of decline of the rapid (Tk1) and slow (Tk2) phase of the curve and the percentage of retention in blood during the 45th minute (R45). The values in a group of normal subjects were 3.4 +/- 0.6 min., 49.1 +/- 8.5 min. and 9.9 +/- 1.7%. In 12 patients with a fully developed clinical picture the liver was visualized intensively and homogeneously within 10 min., in 10 it was enlarged. The intrahepatic biliary pathways were not visualized the passage of activity into the intestinal lumen was delayed above 60 to 120 min., and the increased retention in the liver persisted for more than 120 min. The gallbladder was visualized in six but late and with low intensity. Tk1 was 4.3 to 10.0 min., R45 16.7 to 30.0%. In 9 subjects with the clinically inapparent form the visualization of the intrahepatic pathways was only indicated, the gallbladder was not visualized only in one patient. A protracted retention in the liver was in seven subjects above 60 min., in 2 above 90 min. and in 1 above 120 min. Tk1 was 4.0 to 9.0 min. and R45 12.0 to 27.1%. Hepatobiliary gammagraphy with evaluation of blood clearance of the pharmaceutical preparation is a non-invasive method which helps in the diagnosis of Dubin-Johnson's syndrome. PMID- 2249273 TI - [Thrombocytopenia and thrombocytopathy in neonates and infants]. AB - The authors analyze seven cases of thrombocytopenia and three cases of thrombocytopathies in neonates and infants who were hospitalized within a short period of time at the First Paediatric Clinic in Brno. The results support the view that thrombocytopenia and thrombocytopathies in neonates and infants are fairly frequent. Because they are not manifested by clinical symptoms, their frequency escapes attention. PMID- 2249272 TI - [Cutaneous forms of Lyme borreliosis in children]. AB - Thirty-seven children with skin manifestations of Lyme borreliosis (31 with erythema chronicum migrans and six with lymphadenosis benigna cutis) were treated and followed up prospectivelly for 1-24 months (mean 7.58 months). The diagnosis was confirmed serologically by the finding of increased levels of antiborrelial antibodies assessed by the ELISA method, using antigen from Borrelia recurrentis, in a total of 87% patients with erythema chronicum migrans and in all patients with lymphadenosis benigna cutis. In nine patients the dermatoses were associated with general non-characteristic symptoms, after antibiotic treatment in five patients temporary fatigue, arthralgia and gastrointestinal complaints were observed. No extradermal organ complications were present. The authors discuss the clinical pictures of erythema chronicum migrans and lymphadenosis benigna cutis in children, mention diagnostic criteria and the recommended pattern of treatment. PMID- 2249274 TI - [Differences in the incidence of congenital heart defects in boys and girls]. AB - 4,409 children born in Bohemia (1974-1983) with heart defect were distributed almost between 2,296 (52.1%) boys and 2,213 (47.9%) girls: The boy:girl ratio was 1.09:1. Boys prevailed in double outlet right ventricle (2.68:1), hypoplastic left heart (2.25:1), transposition of the great arteries (2.11:1), aortic stenosis (1.95:1), pulmonary atresia (1.55:1), tricuspid atresia (1.45:1), coarctation of the aorta (1.30:1) and the corrected transposition (1.25:1). Girls prevailed significantly in patent ductus arterious (1.66:1), Ebstein's anomaly of the tricuspid valve (1.57:1), truncus arterious (1.22:1), atrioventricular septal defect (1.17:1) and tetralogy of Fallot (1.12:1). The difference in the remaining heart defects was less than 10%. PMID- 2249275 TI - [Clinical picture of Crohn's disease in children and adolescents]. AB - The authors describe the course of Crohn's disease in two boys and six girls aged 11.1-15.6 years. In three patients with terminal ileitis and affection of the ascendent colon the disease is characterized by prolonged growth retardation, subfebrile temperatures, abdominal pain. For patients with granulomatous colitis, blood-stained diarrhoea is typical abdominal pain and loss of body weight. Three patients were treated first for idiopathic proctocolitis and only in the course of the disease the diagnosis of Crohn's disease was established. In 87.5% of the patients on admission anaemia was found and all patients had a varying elevated red cell sedimentation rate and CRP. The author draws attention to extraintestinal symptoms (dermal, ophthalmological, articular, somatic retardation) which precede in particular somatic retardation) which precede in particular in affections of the small intestine intestinal manifestations. Their erroneous interpretation may delay the establishment of the diagnosis of Crohn's disease. The author emphasizes the importance of basic laboratory examinations and examination by ultrasound for early detection of patients. PMID- 2249276 TI - [Results of phototherapy in neonatal hyperbilirubinemia using green and blue light]. AB - In a group of normal newborns with birth weights of 2500 g and more treated on account of hyperbilirubinaemia the authors recorded a significantly shorter period of decline of serum bilirubin in 40 children with blue light phototherapy than in 40 children with green light phototherapy. The period of decline of bilirubinaemia with green light phototherapy did not differ on average from the period of spontaneous decline recorded in a group of 40 normal neonates with untreated hyperbilirubinaemia. PMID- 2249277 TI - [Spophylin Spofa--tablets with a delayed effect: therapeutic use in the complex therapy of acute bronchitis in infants and toddlers]. AB - In 18 children aged 6-36 months with acute respiratory disease and bronchospasms the authors administered as part of comprehensive treatment Spophyllin tablets with a retarded effect (16-20 mg/kg/hours). Concurrently the theophyllin serum and saliva levels were assessed on the third day of administration. The authors proved a direct relationship between serum and saliva levels. The assessed values in saliva accounted on average for 73.5% of the serum levels. Values in saliva (6 7 micrograms/l ml) were indicators of effective serum values. PMID- 2249278 TI - [Clinical and ethical aspects of growth hormone therapy]. PMID- 2249280 TI - [The physical activity of children in weekly nursery schools]. PMID- 2249279 TI - [Changes in systemic blood pressure and cardiorespiratory parameters in premature neonates during phototherapy]. PMID- 2249281 TI - [Radiation loading in children in radionuclide examinations]. PMID- 2249282 TI - [The importance of artificial hyperventilation in the treatment of neonates with severe postnatal depression]. PMID- 2249283 TI - [Infectious endocarditis in children--contribution of 2-dimensional echocardiography]. PMID- 2249284 TI - [Initial experience with cefotiam in respiratory and urinary tract infections]. PMID- 2249285 TI - [Paralen suppositories for children--a new therapeutic form of antipyretic]. PMID- 2249286 TI - [A portable apparatus for capillary blood collection]. PMID- 2249287 TI - [50 years of hospital pediatrics in Olomouc]. PMID- 2249288 TI - [Comparison of the physical fitness of the young population of Czechoslovakia with similar data from other European countries]. AB - In order to analyze the relationship between VO2 max and height, body mass and lean body mass a multi-longitudinal survey was conducted on three different age groups of randomly selected children from a small Czech community. Beginning at the initial ages of 8, 12 and 16 years subjects were subsequently retested three times at two year intervals. At overlapping ages there were no differences in the various age groups between height and VO2 max. By utilizing mean values for the various parameters at specific calendar ages a growth curve was constructed for each sex for the age range 8 to 20 years. The values were compared with longitudinal studies of various countries and no substantial differences were found. When VO2 max was then compared to height, body mass and lean body mass it was apparent that the almost linear relationship with height was the most precise. In addition the children remained, generally speaking, in their same rank order for VO2 max for the three different age groupings. PMID- 2249289 TI - [Malignant lymphoma of the Burkitt type. Study of 21 cases in childhood]. AB - From a group of 151 malignant lymphomas in childhood the authors selected 21 cases of malignant Burkitt lymphoma. The histopathological diagnosis was checked using common paraffin material, and a basic clinicopathological correlations was made. Malignant lymphoma of the Burkitt type was characterized by a diffuse type of growth with striking cellular cohesion. From the cytological aspect it was uniform with minimal differences in cell size. The presence of macrophages forming a "starry-sky" phenomenon was constant in the bioptic material. It is, however, not specific for Burkitt's lymphoma. In necroptic material macrophages were often absent and the morphology of tumour cells was altered. In the differential diagnosis it is necessary to differentiate in particular malignant lymphoblastic lymphomas and monomorphous centroblastomas. The malignant of Burkitt lymphoma type was localized in the majority of patients in the abdominal cavity, less frequently on the neck and in Waldeyer's ring. The mediastinum was not primarily affected. Five patients survive for 16-52 months after termination of oncological therapy without a relapse. Twelve patients died from generalization of the process, or from complications. Eight of those who died had a primary tumour in the abdominal cavity. The mean interval between the bioptic diagnosis and death was 3.6 months. As to the primary localization of the tumour and some other clinical and pathological data, various authors differ--these differences are discussed in relation to possible variations in the distribution of the tumour under different geographical conditions. PMID- 2249290 TI - [Echocardiographic diagnosis of aortic coarctation in neonates and infants]. AB - Based on experience with the examination of 78 children under one year with coarctation of the aorta the authors present an account of basic echocardiographic examination procedures and findings in this defect. Two dimensional echocardiography revealed in 98.8% of the patients a reduced pulsation of the abdominal aorta, as compared with the pulsation of the ascending aorta. In all instances it proved possible to visualize the coarctation. Pulsed Doppler echocardiography proved an abnormal flow in the abdominal aorta in 89.7% children; at the site of coarctation in 96.1% a typical saw-like flow with an acceleration typical for the flow in a stenotic vessel. Hypoplasia of the aortal arch was recorded in 51.3%, a patent ductus arteriosus in 73.2% of the children. An anomaly of the aortal valve was found in 57.7%, obstruction of the left ventricular, outflow tract in 35.9% children. An anomaly of the mitral valve was present in 23.2% children. M-mode echocardiographic findings proved enlargement of the right ventricle and hypertrophy of its wall. The size of the left ventricle and thickness of its wall differed less from normal values. The width of the aortal root was smaller than in a group of normal patients, the left atrium was enlarged. A combination of echocardiographic methods makes reliable non-invasive diagnosis of coarctation of the aorta in neonates and infants possible, as well as the evaluation of associated defects and indication for operation without the application of invasive methods. PMID- 2249291 TI - [Results of treatment of acute lymphoblastic leukemia over a 12-year period]. AB - In the course of a 12-year period the authors treated at the Paediatric Department of the Regional Institute of National Health in Banska Bystrica 72 children with acute lymphoblastic leukaemia according to four protocols. Complete remission was achieved by 67 children, i.e. 93%. None of the children died from complications of treatment during complete remission. A relapse during treatment or soon after its termination occurred in 23 children, i.e. 31.9%. A second complete remission was achieved in 15 children, i.e. 65.2%. During the second complete remission seven children survive for 0.5-91.5 months. Twenty children died, i.e. 27.8%. All children had at the time of death signs of malignant disease. Fifty-two children survive at present for 1-132 months. The cumulative ratio of surviving children in the 12th year since the diagnosis is 0.57, the cumulative ratio of children in initial complete remission in the 12th year is 0.51. PMID- 2249292 TI - [Pancreatic tumors with endocrine activity in adolescents]. AB - The authors demonstrate three patients--two with a nesidioma of the B-cells with insulin production, the third had a nesidioma made up of non-B cells with clinical manifestations of gastrin hypersecretion. The surgical solution was successful in the patients with B-cell nesiodiomas. PMID- 2249293 TI - [Heart involvement in Lyme borreliosis. Case report]. AB - Lyme disease is a systemic illness with skin, neurologic, joint, and cardiac involvement. Absence of typical skin lesion--erythema chronicum migrans--during the first period of disease may cause the diagnosis difficult. Syncope due to complete atrioventricular block was the first symptom of disease in our patient, but no tick bite anamnestic data were available. Quick changes on EKG tracing during cardiac pacing were present. Echocardiography revealed left ventricular dysfunction. Specific immunological tests confirmed the diagnostic suspicion. Cardiac pacing, digitalis and antibiotic treatment ensued in complete recovery. No other systemic lesion appeared. Lyme carditis may be the only manifestation of the disease. Temporary cardiac pacing may be necessary. PMID- 2249294 TI - [Present views on the regulation of IgE synthesis]. PMID- 2249295 TI - [Active immunization against varicella-zoster virus]. PMID- 2249296 TI - [Prolapse of the mitral valve in children]. AB - The purpose of the paper is a review of contemporary findings on the problem of prolapse of the mitral valve in child age, as it is detected on ultrasonic examination in particular in adolescents. Warth's submitted diagnostic criteria of prolapse of the mitral valve differentiate it from normal closure. When these criteria are not respected, this may lead to unnecessary restriction of physical activity or altered work capacity. PMID- 2249297 TI - [Is it necessary to deal with the gypsy problem in pediatric practice?]. PMID- 2249298 TI - [Prevention and reduction of sensory and motor disorders in childhood. Formulation of the problem]. AB - At present the Scientific and Research Laboratory of Preventive and Social Medicine is concerned with an extensive longitudinal research "Detection and reduction of sensory and motor disorders". Specialists from various paediatrics disciplines and some 200 health community paediatricians from six districts on the CR and SSR participate in the research. The research comprises children born in these districts in one calendar year. In part 1 the authors give an account of the basis formulation of the research problem and its incorporation within a wider framework. The aim of the research is to reduce the incidence and prevalence of sensory and motor disorders or to test techniques of the early detection of symptoms which signalize the risks of various affections, and to create prerequisites for further improvement of the programme of preventive care of the child population. PMID- 2249299 TI - [Disorders of sexual development (2 case report, delayed diagnosis)]. PMID- 2249300 TI - [Intracranial calcification in patients with acute lymphoblastic leukemia]. PMID- 2249301 TI - [Reactive arthritis. Is it a problem only in adults or also in children?]. PMID- 2249302 TI - [Penicillin therapy in pediatrics]. PMID- 2249304 TI - [More on nature schools]. PMID- 2249305 TI - [The program for the campaign against diarrheal diseases in Mongolia]. PMID- 2249303 TI - [Is the use of antimicrobial agents in pediatrics excessive?]. PMID- 2249306 TI - [Diagnosis of aneurysms of the abdominal aorta]. AB - Since 1986 in the radiodiagnostic department of the District Institute of National Health in Lucenec 17 768 abdominal sonographies were made. In the total number of examinations by means of ultrasonography 22 aneurysms of the abdominal aorta were diagnosed, incl. one ruptured one. The high mortality rate on operation of ruptured aneurysms can be reduced in particular by elective resections of non-ruptured aneurysms. Examination of the abdominal aorta should be made as a matter of routine, independently on indication of abdominal sonographic examination, in particular in elderly patients. PMID- 2249307 TI - [Aneurysms of the deep veins of the lower extremities: a rarity or just a less common aspect of other pathological conditions?]. AB - The authors demonstrate four observations of aneurysms of the deep veins of the lower extremities and their differential diagnostic problems. They draw attention to basic technical conditions of their phlebographic visualization and discuss the main mechanisms of their pathogenesis. PMID- 2249308 TI - [Digital subtraction angiography in intracranial vascular malformations]. AB - From a total number of 350 DSA examinations in the cervicocranial region intracranial vascular malformations were detected in 14 patients, i.e. in 4%. In six instances an aneurysm was involved, six times arteriovenous and twice a venous malformation. Using digital subtraction angiography, it is usually possible to diagnose by the intravenous or intraaortal route major findings, however, in the majority the finding serves only for orientation. For a more detailed diagnosis, in particular of small findings and findings before operation, a selective examination is more suitable. PMID- 2249309 TI - [Evaluation of the size of the spleen using computer tomography]. AB - The authors describe the examination, diagnostic possibilities and difficulties associated with the diagnosis of the spleen by means of computed tomography. The finding obtained by computed tomography is evaluated as splenomegaly when two of the three main dimension are greater than the maximal values reported, or when the lienal index is higher than 440. From the practical aspect the decision on splenomegaly is facilitated by the position of the anterior margin of the spleen in relation to the medioaxillary line. Splenomegaly is the most frequent pathological finding on the spleen. The authors give an account of causes of splenomegaly and their own experience with the diagnosis of anomalies, cystic processes, tumours, injuries and obstructions of the lienal vessels. PMID- 2249310 TI - [Varices of the colon in the roentgenologic picture]. AB - The authors describe a double contrast X-ray picture of varicosities of the large intestine. In the literature so far irrigoscopic changes specific for varicosities were not described. The authors observed that the defect of the filling increased after Valsalva's manoeuvre. The authors consider this symptom specific for varicosities. PMID- 2249311 TI - [Activity of administered radiopharmaceutical agents and the radiation burden of the Czechoslovak population caused by nuclear medicine]. AB - The authors assessed by means of questionnaires the activities of radiopharmaceuticals administered in departments of nuclear medicine in Czechoslovakia. The mean activities of individual radiopharmaceuticals are roughly equal as in Great Britain, but lower than in the Canadian province of Manitoba. The differences of activities used in different departments are approximately equal in all compared countries. In the Czech Republic the annual collective effective dose equivalent from nuclear medicine was 433 Sv in 1983 and 609 Sv in 1987. The mean effective dose equivalent per examination was 2.23 mSv in 1983 and 2.44 mSv in 1987. The mean effective dose equivalent per inhabitant of the Czech Republic was 0.042 mSv in 1983 and 0.059 mSv in 1987. The radiation dose of the Czech population from nuclear medicine amounts approximately to one tenth of the load from radiodiagnostics. PMID- 2249312 TI - [Transforming growth factor-alpha in human lung cancer tissue]. AB - 12 cases of human lung cancer tissue were analyzed for the presence of transforming growth factor-alpha with RIA. Histologically 9 were squamous cell carcinoma and 3 were adenocarcinoma. Except one squamous carcinoma, TGF-alpha could be detected in 11 cases. TGF-alpha level was from 0.26 ng to 1.26 ng per gram tissue. There was no significant difference in TGF-alpha level between squamous cell carcinoma and adenocarcinoma. The relationship between TGF-alpha and human lung cancer remains for further study. PMID- 2249313 TI - [Diagnosis of bronchogenic carcinoma with MRI]. AB - MRI anatomy of 15 normal chests and features of 24 patients with bronchogenic carcinoma confirmed by surgery or exfoliative cell examination of sputum were analysed. The authors preliminarily conclude that MRI is of remarkable diagnostic value in demonstrating tumor size, its location and extent, exhibiting the relationship between tumor mass and its surrounding such as greater vessel, trachea and bronchi and so forth. It is also more efficient in detecting hilar or mediastinal metastatic lymphadenopathy. PMID- 2249314 TI - [High risk factors of lung cancer and its early detection]. AB - High risk factors and early detection of lung cancer were studied in a population of greater than 45 years old of 10 122 in Lu Wen District. It was shown as follows: 1. The high risk factors of lung cancer were male greater than 50 years old, and with a smoking history of greater than 400 pack year. 2. Questionnaire 70-110 mm X-ray chest film and sputum cytological examination for the suspicious lung cancer were the screen test for the high risk group. Their prevalence rate of lung cancer was 4.74/1000, 50% of them was in p-staging I, it was 6.3 times higher, than in the specialized hospital, their 5-yr survival rate was 31.5%. It was higher than that in the general population. PMID- 2249315 TI - [Application of thoracoscopy in the diagnosis of pleuro-pulmonary disease]. AB - Thoracoscopic examination was performed in 20 cases of pleuro-pulmonary diseases of uncertain etiology, 16 patients (80%) obtained positive thoracoscopic biopsy results while 4 false negative. Needle pleural biopsy was carried out in 10 cases and four of them gave correct diagnosis. After thoracoscopy thoracotomy were performed in 7 cases and all lesions were resected. Thirteen cases with advanced tumor or benign pleural diseases were treated conservatively. It was concluded that thoracoscopy is as an important technique in diagnosis of pleuro-pulmonary diseases. PMID- 2249316 TI - [Significance of the circulating antibodies in patients with interstitial lung disease]. AB - Indirect immunofluorescent study was proceeded in 86 cases of interstitial lung disease by using human fetal lung as the target organ. 2 kinds of antibodies were found. One was type I or III anticollagen antibody, the positive rate in IPF was the highest, 63%. The other was antinuclear antibody (ANA). 8 cases were positive. Both of the antibodies may play active role in the pathogenesis of IPF. The authors suggest that assessment of the antibodies to college type L & III by immunofluorescent method might be helpful in the diagnosis of IPF. PMID- 2249317 TI - [Pathoanatomical and pathophysiological study of lung injury induced by activated complement in rat]. AB - Acute lung injury induced by intravenous infusion of zymosan-activated plasma(ZAP) on Wistar rats was studied. A single infusion of ZAP resulted in an early occurrence of increased respiratory rate, decreased PaO2, elevated activity of superoxide dismutase(SOD) in the arterial blood and lung tissue. The results showed that the content of copperzinic superoxide dismutase(Cu Zn SOD) in bronchiolar columnar epithelial cells was elevated. Histological and electron microscopic examination showed that there was an accumulation of neutrophils in pulmonary microvessels and capillaries, endothelial cell and epithelial cell injury, and pulmonary edema etc. The tight junctions both in the epithelium and endothelium showed alterations in substructure including discontinuity, irregularity, free ends and distention of meshes as early as 2 to 4 h. In later stage, the severity of damage of tight junctions increased, while the number of strands in endothelial junctions reduced. All the parameters in the control group did not change significantly. From the results, the authors consider that acute lung injury is intimately related to the neutrophils and oxygen free radicals, the pathological basis of early pulmonary edema is alterations in the tight junctions of the alveolar epithelium and capillary endothelium. PMID- 2249318 TI - [Study on the fibrin fibrinogen degradation products levels and it's significance in the phlegm of the patients with chronic cor pulmonale through monoclonal antibodies]. AB - For the first time, we determined the levels of FDP in phlegm of the patients with chronic cor pulmonale and normal subjects by the TRCHII with the McAbs. Antihuman FDP McAb was applied the clinic, hence, the specificity and sensitivity of TRCHII method for detecting FDP was increased, facilitating clinical application. The results showed that the FDP level of the patients was significantly higher than that of normal subjects (P less than 0.05), but there was no significant difference between the levels of the patients of acute stage and those of remission stage. (P greater than 0.05). The main reason for the increased FDP levels in the phlegm of the patients with chronic cor pulmonale is probably due to the pathological change of the disease-recurrent infections, anoxemia, hypercoagulability and so on. The detection of FDP is helpful for the diagnosis, treatment, evaluation of prognosis of the disease. It provides an index for the observation of tissue damage of lung, especially the damage of capillary endothelia of the lung. PMID- 2249319 TI - [Pulmonary changes in progressive systemic sclerosis]. AB - The pulmonary changes of progressive systemic sclerosis in 8 cases were reported. The major clinical complaints were unproductive cough and exertional dyspnea. Pulmonary function tests showed restrictive ventilatory defects and impaired diffusing capacity in most of the cases examined. On chest X-rays, diffuse mottling and linear densities were seen in lungs, predominately in the basal regions. On pathological examinations, pulmonary interstitial fibrosis occurred in early stage of the disease. The results showed that pulmonary involvement may be an early event in progressive systemic sclerosis. PMID- 2249320 TI - [Preliminary report of short-course tuberculosis of the spine]. AB - This study consisted of 149 newly diagnosed cases of tuberculosis of the spine; these were alloeated into the following two regimens: 4SHER/5HER and 4SHER/5H3E3R3. 145 cases have completed their chemotherapy. In patients (2.7%) the allocated regimens was modified because of adverse reactions. All of the patients except 9 cases, operative debridment of the spinal focus was performed within 1-3 months of the start of chemotherapy. Some of the results from this study were encouraging: (1) the therapeutic response was favourable in both regimens, and adverse reactions, mainly hepatic toxicity, were rather low, (2) after a four-month initial intensive phase, both intermittent administration for 5 months or daily treatment for 5 month in the continuation phase were of the same high efficacy at the end of treatments as well as during 4-44 months follow up. PMID- 2249321 TI - [Effects of rifamdin on pharmacokinetics of dexamethasone]. AB - The rabbits of same sex and approximate weight, were randomly divided into following two groups: a group given all rifamdin for 12 days before dexamethasone injection and a control group without RFD. After a single IV injection of dexamethasone sodium phosphate, the concentrations of dexamethasone in rabbit plasma taken at 5, 15, 30 min, and 1, 2, 4, 8 h were analysed by reversed phase HPLC-UV. Linear regression analysis was made by LnC(t)-t. The pharmacokinetic parameters of dexamethasone in rabbits were calculated by methods of residuals. The results of main parameters, i.e. K10, beta, T1/2 beta, cls and AUD0-infinity kg-1 showed that rifamdin apparently promotes metabolic clearance of dexamethasone in plasma. PMID- 2249322 TI - [Clinical significance of ultrasonography in detecting pleural effusion]. AB - 159 cases of pleural effusion due to various pathogenic factor are presented. 80 patients with tuberculous pleural fluid were examined by both ultrasonography and radiography, of which 30 cases were explored with B-mode and A-mode ultrasonography. Though the result of thoracentesis it was showed that the sensitivity of B-mode ultrasonography was apparently higher than those of A-mode and X-ray. We feel that B-mode ultrasonograph has a particular diagnostic value of identifying multilocular pleural effusion, small amount, encapsuled effusion and thickened pleura with small amount of fluid. Mean time, it can give a clear view and a quick measurement of thickness of the pleura. PMID- 2249323 TI - [A clinical study on 65 cases with tracheobronchial tuberculosis]. AB - We recently diagnosed 65 cases with tracheobronchial tuberculosis using fiberbronchoscope. All the patients presented TB symptoms and were smear positive, some of them had been misdiagnosed for chronic bronchitis or lung cancer. Among them, 16 cases were simple tracheobronchial tuberculosis (24.6%) without TB lesions in the lungs. The results show that fiberbronchoscopic examination is a good method to diagnose tracheobronchial tuberculosis and distinguish lung cancer by direct observation of tracheobronchial lostons or brush biopsy for TB. PMID- 2249324 TI - Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer. AB - In this study the influence of amino-glutethimide (AG) on the disposition of medroxyprogesterone acetate (MPA) and megestrol acetate (MA) was studied. When 1,000 mg AG daily was supplementally given to six patients on chronic treatment with MPA (1,000 mg/day) or MA (160 mg/day), mean serum levels of progestin were reduced by 74% as compared with control levels (P less than 0.03). AG did not change the blood clearance rate of MPA when the latter was given i.v. This discrepancy between AG's influence on oral and parenteral progestin disposition could be explained by pharmacokinetic properties of the progestins, and our results suggest that AG stimulates the metabolism of progestins. The decrease in MPA and MA serum levels was accompanied by an increase in serum cortisol, sex hormone-binding globulin (SHBG) and testosterone levels. This suggests that AG reduces the biological activity of progestins. PMID- 2249325 TI - The comparative disposition of [14C]-fotemustine in non-tumourous and tumourous mice. AB - The distribution and excretion of radioactivity from [14C]-fotemustine was examined in mice with melanomas at different stages of development to determine whether the disease state substantially alters the disposition of the drug and its metabolites. Normal BDF1 mice and mice that had been subcutaneously grafted with B16 melanoma either 1, 3, 7, 14 or 21 days previously were used. The animals were killed at either 5 min, or at 3, 24 or 96 h after receiving an intravenous dose of [14C]-fotemustine (20 mg/kg) and were examined either by whole-body autoradiography or by liquid scintillation counting of excreta and tissues of interest. The majority of the [14C]-fotemustine dose was excreted in the urine, with similar amounts being measured in both non-tumourous animals (61.6% +/- 13.1%) and tumourous mice grafted 14 days previously (67.2% +/- 5.7%). Small amounts of radioactivity, again similar in both non-tumourous and tumourous mice, were recovered in the faeces (5.4% +/- 5.6% and 3.6% +/- 1.8%, respectively) and as carbon dioxide (7% +/- 3.5% and 6.4% +/- 1%, respectively), with minimal amounts being expired as chloroethanol (less than 1%). When mice were examined 5 min after dosing, there was extensive tissue distribution accounting for 75% +/- 10% of the dose. The highest concentrations determined by both whole-body autoradiography and liquid scintillation counting were measured in the excretory organs, with 33 and 28 micrograms Eq/g being found in the liver and kidney, respectively. High levels were also seen in the lung and plasma (19.8 and 19.5 micrograms Eq/g, respectively). Analysis of variance indicated that groups of tissues, such as the excretory organs, blood and plasma or the pigmented tissues, showed distinct but inconsistent patterns. Only tumours at 14 and 21 days of development were suitable for examination, and these showed levels of 12.1 micrograms Eq/g; however, the tumour-to-plasma ratio increased from between approx. 0.5 and 0.6 at 5 min to approx. 2 at 96 h after dosing, suggesting retention within the melanoma, whereas the ratio for the femur remained at approx. 1. Whole-body autoradiography showed that the distribution in the tumour was not uniform, but rather was concentrated in the peripheral area (presumably viable cells) as opposed to the central necrotic region. Thus, the high and sustained concentration of radioactivity found in the active cells of the melanoma may provide an explanation for the high efficacy of the drug. PMID- 2249326 TI - A new intraperitoneal tumor model in the rat. AB - A new tumour model that is particularly suitable for testing intraperitoneal chemotherapy is described. Single tumours were induced to grow in the mesentery of rats by the implantation of small pieces taken from subcutaneous tumours. Tumour growth was monitored by repeated laparotomies at which the tumour size was measured with calipers. In this way, growth curves of treated and untreated tumours could be defined. The diameter of untreated intraperitoneal tumours increased linearly with time [diameter (mm) = 0.39 t (days) +2.4]. Tests using different numbers of laparotomies showed that the procedure itself had little influence on growth. Cell kinetic studies of 6-mm tumours showed a mean labelling index of 31% and a volume-doubling time of 3.9 days, resulting in cell-loss factors probably in excess of 70%. The model was tested by assessing the effect of the chemotherapeutic agent cisplatin. Regression and regrowth could be satisfactorily followed, leading to estimates of growth delay. This model therefore provides a quantitative way to assess the response of intraperitoneal tumours to chemotherapy. PMID- 2249327 TI - The effect of cimetidine on cyclophosphamide metabolism in rabbits. AB - Six female rabbits were given 20 mg/kg cyclophosphamide (containing 100 microCi [3H-chloroethyl]-cyclophosphamide) alone or 1 h following 100 mg/kg cimetidine. Serial plasma and urine specimens were collected and levels of cyclophosphamide and its metabolites (4-hydroxycyclophosphamide, 4-ketocyclophosphamide, phosphoramide mustard, and carboxyphosphamide) were measured. 4 Ketocyclophosphamide was the major metabolite present in rabbit plasma and urine, with lesser amounts of 4-hydroxycyclophosphamide, carboxyphosphamide, and phosphoramide mustard also being identified. Cimetidine pretreatment resulted in prolongation of cyclophosphamide's half-life from 24.3 +/- 7.3 to 33.5 +/- 9.5 min (mean +/- SD; P = 0.036) but did not significantly alter the AUC0-8 h for the latter drug. Cimetidine pretreatment resulted in a significantly greater AUC0-8 h for 4-hydroxycyclophosphamide (189.4 +/- 77 vs 364.6 +/- 126.7 mumol min/l-1; P = 0.016) as compared with control values. A higher AUC0-8 h value for phosphoramide mustard (53.7 +/- 69.2 vs 95.7 +/- 34.7 mumol min/l-1) was also observed after cimetidine dosing but the difference was not significant (P = 0.21). Kinetics of 4-ketocyclophosphamide and carboxyphosphamide were not significantly affected by cimetidine treatment. Cimetidine was added to hepatic microsomes isolated from phenobarbital-treated rabbits; it did not inhibit cyclophosphamide's metabolism in vitro, suggesting that its in vivo effect may be mediated through mechanisms other than cytochrome P-450 inhibition. Cimetidine pretreatment increases exposure to cyclophosphamide and its major activated metabolite, 4 hydroxycyclophosphamide. Potentiation rather than inhibition of cyclophosphamide's pharmacodynamic effect is to be predicted when cimetidine is given concomitantly with the former. Alterations in hepatic blood flow or mechanisms other than microsomal inhibition by cimetidine may explain this potentiation. PMID- 2249328 TI - Phase I trial of 5-fluorouracil, leucovorin, and cisplatin in combination. AB - The ongoing evaluation of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in several tumors prompted a phase I clinical trial of cisplatin with 5 FU modulated by leucovorin. A total of 26 patients were treated with varying doses of 5-FU by continuous i.v. infusion for 5 days; 200 mg/m2 leucovorin was given by daily bolus injection for 5 days; and 20 mg/m2 cisplatin was infused over 2 h on each day of treatment. Courses were repeated every 21-28 days. The starting dose of 5-FU was 300 mg/m2. Poor-risk patients (extensive prior radiation, performance status of 2 or worse) did not tolerate the initial dose; the maximum tolerated dose of 5-FU in this group was 200 mg/m2 daily. Good-risk patients tolerated 300 mg/m2, but a majority had excessive toxicity at higher doses. The dose-limiting toxicity was gastrointestinal (mucositis/diarrhea) and/or myelosuppression; additional side effects included were nausea and vomiting (less than or equal to grade 2) and ataxia (one patient). Among 13 patients with colorectal cancer, 4 partial responses were observed. The marked reduction in the tolerable dose of 5-FU occasioned by the addition of modulating doses of leucovorin is noteworthy. The responses observed support further investigation of this regimen in phase II trials. PMID- 2249329 TI - Intratumoural administration of cisplatin in slow-release devices. I. Tumour response and toxicity. AB - In this study we investigated the effect of the incorporation of cisplatin in slow-release systems on tumour response and animal toxicity after intratumoural (i.t.) administration. Solid slow-release rods with incorporated cisplatin were prepared either from starch or from three different polyether-hydrogel formulations. In vitro release rates from these rods were widely different. With the starch system, approximately 100% release was obtained in 2 h. For the hydrogel formulations, release was approximately 100% in 1 day for a formulation with 40% water uptake (T3), 45% within 4 days for a formulation with 14% water uptake (T2) and 8% within 4 days for a formulation with 4% water uptake (T1). The slow-release rods containing graded amounts of cisplatin were implanted i.t. in s.c. RIF1 murine tumours. The i.t. administration of cisplatin in starch rods did not reduce animal toxicity or increase tumour response relative to i.t. injections of cisplatin in solution. For the hydrogel rods, the tumour response and animal toxicity for a given dose of cisplatin decreased with decreasing release rate. Higher doses of cisplatin could therefore be delivered with the slower-releasing hydrogel formulations. The slowest-release hydrogel rods (T1) had very little effect on either tumour (growth delay) or host (animal weight loss), even at cisplatin doses 8 times that tolerated as an i.p. injection. The fast (T3)- and intermediate (T2)-release hydrogel rods resulted in dose dependent tumour growth delays that were longer than those obtained with i.p. or i.t. administration of cisplatin. The highest response, a tumour growth delay of 55 days, was obtained with the intermediate-release hydrogel rods (T2) at a cisplatin dose of 40 mg/kg. Analysis of tumour growth delay for a given level of toxicity indicated that the intermediate-release formulation (T2) was slightly better than the fast-release formulation (T3) and confirmed the therapeutic advantage of i.t. implants over systemic therapy. PMID- 2249330 TI - Cellular pharmacology of 1-beta-D-arabinofuranosylcytosine in human myeloid, B lymphoid and T-lymphoid leukemic cells. AB - The in vitro inhibitory action and metabolism of 1-beta-D arabinofuranosylcytosine (ara-C) on human myeloid (HL-60), B-lymphoid (RPMI 8392), and T-lymphoid (Molt-3) leukemic cells was compared. Ara-C produced greater inhibitory effects in Molt-3 cells than in either HL-60 or RPMI-8392 cells. At a 48 h exposure, ara-C was 7 and 10 times more cytotoxic to Molt-3 cells than to HL-60 and RPMI-8392 cells, respectively. The total ara-C uptake to nucleotides and the formation of 1-beta-D-arabinofuranosylcytosine 5' triphosphate (ara-CTP) was about 5 times greater in Molt-3 cells than in either HL-60 or RPMI-8392 cells. The incorporation of ara-C into DNA was also higher in Molt-3 cells than in either HL-60 or RPMI-8392 cells. The mean intracellular half life of ara-CTP was 31.7, 59.4, and 155 min for RPMI-8392, HL-60, and Molt-3 leukemic cells, respectively. The Km and Vmax values of ara-C for deoxycytidine kinase and the feedback inhibition of this enzyme by ara-CTP in the different leukemic cell lines could not explain the differences in metabolism of this analogue in these cells. These data indicate the increased sensitivity of T lymphoid leukemic cells to ara-C than as compared with B-lymphoid and myeloid leukemic cells was due to an increased rate of formation and a longer half-life of ara-CTP in the T-cells. PMID- 2249331 TI - Metabolism of epirubicin to glucuronides: relationship to the pharmacodynamics of the drug. AB - In pharmacokinetic studies of epirubicin, we observed that its main metabolite, epirubicin glucuronide, presented a marked interpatient variation. It was even possible to separate the patients into two groups: those with a high epirubicin glucuronide:epirubicin plasma ratio and those with a low ratio, with few patients in between. We retrospectively analyzed the clinical files of 48 patients who had been subjected to a pharmacokinetic study of epirubicin. We observed that those with a low epirubicin glucuronide:epirubicin ratio had significantly lower plasma levels of fibrinogen and alpha 2-globulins, suggesting that a reduced glucuronidation of epirubicin could be associated with hepatocellular insufficiency. These patients also had significantly lower percentages of change in granulocytes after therapy and responded better to the course of treatment studied. We cannot presently propose a hypothesis to explain these observations. PMID- 2249332 TI - A simplified assay for measurement of cytosine arabinoside incorporation into DNA in Ara-C-sensitive and -resistant leukemic cells. AB - The assays for the detection of unlabeled 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside, Ara-C) incorporation into DNA was simplified. The procedure includes DNA isolation from leukemic cells, quantification of DNA concentrations, breakdown by enzymatic digestion of DNA to nucleosides and a radioimmunoassay (RIA) using an antibody against Ara-C. Different techniques for quantification of DNA concentrations are compared. A fluorimetric technique using Hoechst 33258 is preferred because it is the most specific method. Comparison of this RIA assay with measurement of [3H]-Ara-C/DNA formation under similar conditions in HL-60 cells showed a correlation of 0.99. Ara-C incorporation into DNA of leukemic cells was studied using two rat-leukemia cell lines, one of which is sensitive to Ara-C and the other is an Ara-C-resistant wild type: BNML-Cl/0 and BNML-Cl/Ara-C, respectively. The results showed that Ara-C is incorporated when the cells are incubated at concentrations equal to or higher than the Ara-C concentration that induces 50% growth inhibition after 48 h incubation (IC50). This implies that at lower Ara-C concentration, i.e. levels that do not induce cytotoxicity, Ara-C is not incorporated into DNA. Similar results were obtained with human HL-60 myeloid leukemia cells. The detection limit of this assay is 2 pmol/ml Ara-C; therefore, the assay is more sensitive than measurement of Ara-C triphosphate (Ara-CTP), the only metabolite that can be measured in leukemic cells from patients after in vivo Ara-C administration. On the basis of in vitro studies, the finding of detectable Ara-C/DNA levels in vivo is expected to correlate with cytotoxicity; whether or not the Ara-C/DNA level itself is informative remains to be evaluated. PMID- 2249333 TI - Alteration of dacarbazine pharmacokinetics after interleukin-2 administration in melanoma patients. AB - In an effort to improve the treatment of metastatic malignant melanoma, we evaluated the sequential administration of the chemotherapeutic agent dacarbazine (DTIC) and the biological response modifier interleukin-2 (rIL-2) in a phase I-II study. Since the combination of biological response modifiers and chemotherapeutic agents could alter drug disposition, we evaluated the pharmacokinetics of DTIC and its major metabolite, 5-amino-imidazole 4 carboxamide (AIC), before and after rIL-2 administration. DTIC (1 g/m2, 24-h i.v. infusion) was given on day 1 and rIL-2 (2-4 million Cetus units/m2, 30-min i.v. injection), on days 15-19 and 22-26 of each course of therapy. The second DTIC dose was given on day 29, i.e., 3 days after the last rIL-2 administration. DTIC and AIC were assayed by reversed-phase HPLC. DTIC plasma levels showed a significant decrease after rIL-2 administration as compared with DTIC values obtained in the same patients before rIL-2 administration. DTIC area under the curve (AUC) values obtained after rIL-2 were lower than those obtained on day 1 before rIL-2 administration (P = 0.02). After rIL-2, the total body clearance (ClT) was increased (P = 0.04), as was the volume of distribution at steady state (Vss; P = 0.02). The decrease in AUC after rIL-2 administration became more pronounced as the rIL-2 dose was increased (P = 0.03). No significant difference was detected in the elimination phase of DTIC when half-lives obtained before and after rIL-2 administration were compared; the mean half-lives were 0.7 and 2.8 h for the alpha- and beta-phases, respectively. The model-independent mean residence time was 3.4 h. The plasma AUC for the metabolite AIC did not charge after rIL-2 administration. AIC biphasic plasma elimination was also similar after rIL-2 administration, with alpha- and beta-half-lives of 0.7 and 11.4 h, respectively. Urinary excretion of DTIC and AIC did not differ after rIL-2 administration; the overall DTIC excretion was 39% of the dose over 48 h, and AIC urinary excretion was 25% of the DTIC dose. The observed decrease in the DTIC plasma AUC after rIL-2 administration appears to be due to an increase in the volume of distribution, since other factors such as half-lives, urinary excretion, and metabolism were not significantly altered. The clinical consequences of the rIL-2-DTIC interaction remain difficult to assess based on presently available data, but this drug interaction should be taken into consideration in the development of future chemo-immunotherapy regimens that include high-dose rIL-2. PMID- 2249334 TI - VIM-D salvage chemotherapy in Hodgkin's disease. AB - A total of 15 patients with relapsed or resistant Hodgkin's disease were treated with a combination of etoposide (VP16), ifosfamide, mitozantrone and dexamethasone (VIM-D). The regime was well tolerated, the only major toxicity being myelosuppression. Complete remissions (CRs) were obtained in 4 patients and were maintained for 2, 4, 10 and 14 months. 10 subjects subsequently received an autologous bone marrow transplant with high-dose chemotherapy (ABMT). Previous exposure to VIM-D did not appear to predict for or prejudice the response to subsequent ABMT. PMID- 2249336 TI - Hydroxyurea-induced acute alveolitis in a patient with chronic myeloid leukaemia. AB - A number of cytotoxic agents have been implicated in the production of widespread pulmonary alveolar damage. We present a case of life-threatening alveolitis in a patient on hydroxyurea for chronic myeloid leukaemia. The clinical course suggests that the alveolitis was induced by the hydroxyurea. This is the first reported case of hydroxyurea-induced pulmonary alveolitis. PMID- 2249335 TI - 7-Hydroxymethotrexate concentrations in serum and cerebrospinal fluid of children with acute lymphoblastic leukemia. AB - Concentrations of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) were determined by HPLC in the serum and cerebrospinal fluid (CSF) of 29 children with acute lymphoblastic leukemia. CSF and serum samples were obtained at the end of 104 infusions of MTX given in a dose range of 0.5-8.0 g/m2. Concentrations, distribution ratios in serum and CSF for MTX and 7-OH-MTX, and the metabolic index were analyzed with regard to the MTX dose, age and clinical state of the patients. A wide inter-patient (2- to 12-fold) but narrower (1.1- to 3.5-fold) intra-patient variability of the concentrations was observed. A dose-proportional increase in the metabolite concentration was found in serum. On the other hand, the elevation of the level of metabolite in CSF was less than proportional to the dose. The CSF/serum distribution data suggest the existence of a saturable carrier system for MTX and 7-OH-MTX between serum and CSF that has lower affinity for 7-OH-MTX. No correlation was found between concentrations of MTX and 7-OH-MTX in the serum of patients receiving the same dose of MTX. No significant difference was observed in the values for metabolic index between relapsed patients and those who were in continuous complete remission. A significant correlation was found between age and metabolic index: the younger the patient, the higher the metabolite concentration measured in serum. PMID- 2249337 TI - Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group. AB - A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites. PMID- 2249338 TI - Combination salvage chemotherapy using cisplatin and teniposide for patients with refractory germinal testicular tumors. AB - Ten patients with refractory germ-cell tumors were treated with a chemotherapy regimen consisting of teniposide and cisplatin (VM-26 and CDDP; P-VM therapy). Three patients (30%) achieved a complete remission (CR) after chemotherapy alone, and another three subjects (30%) attained a CR following chemotherapy and radiation therapy. Three of the six complete responders relapsed but were rendered disease-free by re-salvage therapy. Among the responders, six patients (60%) are alive and remain disease-free after follow-up periods ranging from 18 to 84 months (median, 48 months). However, the toxicity of P-VM therapy was high, with severe myelosuppression being observed in nine patients; nevertheless, all side effects were reversible. We concluded that the P-VM regimen seems to be effective in the treatment of refractory testicular cancers. PMID- 2249339 TI - Inflammatory carcinoma of the breast: results of a combined-modality approach- M.D. Anderson Cancer Center experience. AB - A total of 106 patients with inflammatory carcinoma of the breast underwent combined-modality treatment consisting of doxorubicin-containing chemotherapy. All patients received three cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) before local therapy. From 1974 to 1977 (group A), primary radiotherapy was the local treatment modality and chemotherapy was given for a total of 24 months. From 1978 to 1981 (group B), mastectomy became the primary local treatment modality and FAC was reinstituted within 10-14 days after surgery; after completion of FAC, consolidation radiotherapy was given. From 1982 to 1986 (group C), vincristine and prednisone were added to FAC, and doxorubicin was given by continuous infusion. The median follow-up of the three groups was 56 months. For patients alive at the time of analysis, median follow-ups were 141, 111, and 49 months in groups A, B, and C, respectively. Disease-free survival at 5 years was 35%, 22%, and 41% for groups A, B, and C, respectively, and respective overall survival at 5 years was 37%, 30%, and 48%. Mastectomy in addition to radiotherapy resulted in local control rates similar to those obtained with radiotherapy alone, but this approach would result in fewer late sequelae of high-dose irradiation and provided histologic staging for chemotherapy response. The patients treated on protocol C had slightly better disease-free and overall survival, but the differences were not statistically significant. The 5-year disease-free survival of patients achieving a clinical complete remission (CR) or partial remission (PR) was superior to that of patients whose response was less than a PR. There was no episode of doxorubicin related cardiac toxicity in group C. Combined-modality treatment for inflammatory carcinoma of the breast resulted in improved survival. PMID- 2249340 TI - Ethics. PMID- 2249341 TI - Collagen shields. PMID- 2249343 TI - Reservations about disposable contact lenses. PMID- 2249342 TI - The "ideal" contact lens. PMID- 2249344 TI - Computer assistance in keratoconus lens design. AB - In the past, keratoconus patients have been custom fit with multi-curve spherical contact lenses. Recently it has become possible to commercially manufacture aspherical contact lenses of high-Dk material. A computer assisted fitting technique may be used with these new lenses. We report 90 consecutive keratoconus eyes that were fit with aspherical high-Dk contact lenses using a computer-aided fitting system. Mild and severe grades of keratoconus cases were included, with a 6 to 12 month follow-up time. The combination of new lens geometry and lens material produced a reduction in corneal complications. The asphericity of the lens geometry had a slight negative influence on the visual acuity in mild keratoconus cases, but the visual acuity in the severe keratoconus cases was good. The contact lens material proved acceptably durable, despite the high oxygen transmissibility. We found the computer assisted fitting technique very accurate in determining the initial fitting lens and much faster than the former trial-and-error procedure. PMID- 2249345 TI - Corneal infiltrates associated with disposable extended wear soft contact lenses: a report of nine cases. AB - We report nine cases of corneal infiltrates and/or ulceration in patients using disposable extended wear contact lenses. None of the nine patients had worn the lenses more than the recommended 7 days. Cultures were performed on six of the patients; all cultures were negative. One of the six cultured patients had been treated with topical antibiotics prior to culture. All responded promptly to cessation of lens wear and topical antibiotic therapy. Although all of the infiltrates/ulcers were paracentral, none of the patients sustained any permanent visual loss. PMID- 2249346 TI - Contrast sensitivity in extended wear of the Boston IV lens. AB - Over a one-year period we evaluated subjective and objective factors associated with extended wear of Boston IV rigid gas permeable contact lenses. Patients wore the lens on an extended wear schedule, with removal at 2-week intervals for cleaning. We performed keratometry and endothelial cell counts and measured visual acuity, contrast sensitivity, refraction, and corneal thickness at the initial visit (with patients wearing their former glasses or soft or hard lenses) and again at 6 and 12 months (with patients wearing the Boston IV lens). Twenty four of 31 patients (77%) completed the study. All measured parameters were checked for statistically significant change over time. Contrast sensitivity increased at all spatial frequencies tested, with the largest increments occurring at higher frequencies (P less than .001). The other parameters showed no significant changes (P greater than .05). Our data support the use of contrast sensitivity for qualitative assessment of visual function among contact lens wearers and suggest that contrast sensitivity testing may prove to be a more effective means of evaluating visual acuity in contact lens wearers over time than Snellen acuity. PMID- 2249347 TI - Use of gas permeable contact lenses following trabeculectomy. AB - Some patients require a contact lens after glaucoma filtering surgery. The visual rehabilitation of such eyes can be challenging. We report on a total of eight eyes (seven patients) fit with lenticular-design, rigid gas permeable (RGP) contact lenses after the successful establishment of a filtering bleb. In follow up (mean: 40 months), all patients have successfully worn lenses without adverse effects. We believe that, with careful fitting, close monitoring, and appropriate patient selection, the presence of a filtering bleb need not be a contraindication to contact lens wear, particularly when a smooth-edged, rigid gas permeable (RGP) daily wear lens is used. PMID- 2249348 TI - Contact lens materials: a critical review. AB - The development of contact lenses has been guided, in large measure, by the effort to produce lens materials that provide sufficient oxygen to the cornea. The prime obstacle to those efforts has been that attainment of high oxygen transmissibility has necessitated the compromise of other essential properties, such as wettability and resistance to deposits. This article reviews the history and current status of efforts to manufacture a lens material that will provide a balance among all of these properties. In addition, consideration is given to the complications associated with extended wear of contact lenses and practical ways of minimizing those complications, even in the absence of a lens material that is ideally suited for this purpose. PMID- 2249349 TI - Effects of sighting and sensory dominance on monovision high and low contrast visual acuity. AB - We investigated the relationship between ocular dominance and monovision visual performance in 15 presbyopic subjects. Ocular dominance was determined using sighting (hole-in-the-card and mirror tests) and sensory (anisometropic blur suppression test) methods. Correcting the dominant sighting eye for a given viewing distance was found to be an unreliable method of optimizing blur suppression or binocular high/low contrast visual acuity at that distance. If there is any advantage to a particular strategy for selecting the distance monovision eye, it must be realized in vision performance areas other than visual acuity. PMID- 2249350 TI - Pseudostrabismus secondary to use of cosmetic contact lenses. AB - The DuraSoft 3 Colors cosmetic contact lens is manufactured with a pattern of opaque dots applied to its front surface in order to produce a change in apparent iris color. We fit ten subjects with the DuraSoft 3 Colors contact lens, and all were found to have pseudoexotropia. The deviation ranged from 10 to 22 delta (prism diopters) (average: 16 delta). The cause of the pseudoexotropia was creation of a pseudopositive angle kappa from lateral displacement of the contact lens. Physicians fitting the DuraSoft 3 Colors contact lens should pay special attention to centration characteristics during the fitting session in order to avoid creation of pseudostrabismus. PMID- 2249351 TI - Effect of recipient lamellar keratectomy on corneal topography in penetrating keratoplasty. AB - Recipient tissue weakness is thought to be a cause of the high residual astigmatism that may follow penetrating keratoplasty (PK). In a rabbit model, we investigated the topographic effect of a controlled lamellar keratectomy (6 x 3 x 0.25 mm) on the recipient side following PK. Results from 10 animals indicate an overall flattening of 5 D along the axis of the keratectomy--i.e., the axis of recipient tissue weakness. Our results indicate that recipient corneal integrity may be a factor in corneal transplant topography. PMID- 2249352 TI - Tight lens syndrome with extended wear contact lenses. PMID- 2249354 TI - Immunodermatology. PMID- 2249353 TI - Organization of the human immune system. AB - During the past decade, our knowledge concerning immunologic development and function has expanded rapidly as a result of the interplay between fundamental studies of antigen receptors and lymphokine molecules and the genes encoding them and studies of patients with leukemias, autoimmune disorders, and immunodeficiency diseases. The latter have been particularly valuable in defining the critical stages in the differentiation of stem cells into mature lymphoid effector cells and the roles played by different subpopulations of cells in regulating immune responses. Several categories of defects in these cellular maturation and cellular interaction events lead to immunodeficiency diseases, including intrinsic defects in the lymphoid cells; abnormalities in the microenvironments necessary for the generation of the differentiation signals essential for the maturation of lymphoid cells; disorders of regulatory cells that normally control humoral and cellular immune responses; and, finally, disorders in which the production of lymphoid cells and immunoglobulins is normal but in which host environment abnormalities lead to excessive endogenous catabolism or excessive loss of immune elements. A second area of major advance has been in defining the arrangement of immunoglobulin and T-cell receptor genes. These genes in their germline form are organized as discontinuous DNA elements that are joined by recombinations during lymphocyte development. The analysis of immunoglobulin gene structure and arrangement has contributed to the study of human lymphoid neoplasms. In addition, the analysis of rearranged immunoglobulin and T-cell receptor genes has been valuable in defining the lineage (T or B cell) of neoplasms whose origins were previously unknown; in determining the clonality of abnormal lymphocyte proliferation; in diagnosing and monitoring the therapy of lymphoid malignancies; in determining the state of maturation and the causes for failure of maturation of cells of the B-cell series; and in providing insights into the causes of malignant transformation of B and T lymphoid cells. It is apparent that the application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia. A final area of dramatic advance has been in defining an array of lymphokine molecules that regulate T-cell and B-cell growth and differentiation. One of the best studied of these lymphokine systems is that of IL-2 and its receptor. Antigen-induced activation of resting T cells induces the synthesis of IL-2 as well as the expression of specific cell surface high-affinity receptors for this lymphokine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249355 TI - The complement system. Activation, modulation, and clinical relevance. AB - Activation of the classic or the alternative pathway of the complement system results in the generation of biologically active products and the assembly of MAC. Homeostasis is achieved by the presence of control proteins that modulate the activation at various levels. Complement proteins play an important role in the pathogenesis of several dermatologic disorders. Their deficiency is associated with impairment of host-defense; uncontrolled activation of the system results in the development of angioedema or chronic hemolysis. PMID- 2249356 TI - IgE and immediate hypersensitivity. AB - Tissue mast cells play a central role in immediate hypersensitivity reactions. The clinical manifestations of these reactions appear to be dependent, in large part, on the anatomic location of the stimulated mast cells and the type of mediators released. In vivo and in vitro studies indicate that the tissues in which mast cells reside may greatly influence their biochemical composition, expression of surface receptors, and response to potential stimuli. Although all human mast cells in different organs store similar concentrations of histamine, heparin, and tryptase, cutaneous mast cells appear to be the predominant source of mast cell-derived chymase. Furthermore, at the time of stimulation, human skin mast cells predominantly form PGD2, whereas lung and intestinal mast cells generate LTB4, LTC4, and PGD2. Functional studies indicate that human cutaneous mast cells differ from human lung, heart, and intestinal mast cells. Skin mast cells are responsive to a variety of immunologic and nonimmunologic stimuli in vitro, whereas human pulmonary, cardiac, and intestinal mast cells are relatively refractory to many of these stimulatory signals. Taken together, these observations indicate that mast cells may assume different, and possibly specialized, functions within a specific tissue. Such site-to-site variation potentially could have important clinical significance, to the extent that information gained from mast cells in one organ may not be applicable to a mast cell population in a different tissue. Furthermore, these differences among human mast cells may not be confined to their biochemical composition and responses to various stimuli, but also may extend to the effectiveness of different anti allergic preparations. Therefore, these observations underscore the importance of continued detailed investigation of human mast cells from different anatomic sites. PMID- 2249357 TI - Keratinocyte cytokines and growth factors. Functions in skin immunity and homeostasis. AB - Evidence has been presented to support the theory that the KC, by virtue of its production of cytokines and growth factors, is an integral component of the immune system. The production of cytokines by the KC is normally carefully regulated in order to maintain normal body homeostasis. Malfunction of the regulatory processes controlling cytokine release may result in the development of skin disease. PMID- 2249359 TI - Dendritic cells of the skin. AB - The dendritic shape of a given cell is by no means indicative of its origin and function. This is exemplified best by the ontogenetic and functional heterogeneity of dendritic cells in the skin. Even when focusing on bone marrow derived dendritic cells, the mammalian skin contains at least three distinct lineages of dendritic cells, including Ia+ nonlymphoid dendritic cells (epidermal and dermal Langerhans cells, veiled cells in the lymphatics), dendritic epidermal T cells (mouse), and less well-characterized dermal dendrocytes. Methods exist that allow us to isolate and to purify these cells, to study their phenotype and function, and, thus, to clarify their role in both physiologic and pathologic conditions of the skin. PMID- 2249358 TI - T-cell antigen receptors. AB - We have reviewed the knowledge of the human TCR and its implications in dermatology. The TCR has been shown to be the molecule responsible for specific cellular immunity in the same way that immunoglobulins confer humoral immunity. Much has been learned about the complex genomic organization of the TCR chains and how the great diversity of TCR proteins is created by somatic rearrangement of the genes. Most peripheral T cells carry an alpha/beta TCR heterodimer; these cells account for the major T-cell-associated functions such as cytolysis and the modulation of immune responses. The gamma/delta TCR is found on a minor population of T cells, and its functional significance needs further characterization. With respect to dermatology, the knowledge of TCR genetics, along with the application of recombinant DNA methodology, has provided a major improvement in the diagnosis and management of mycosis fungoides. Sezary's syndrome, and other lymphoproliferative diseases of the skin. PMID- 2249360 TI - Pemphigus. AB - Pemphigus is an autoimmune intraepithelial blistering disease of the skin and mucous membranes that is characterized in part by the presence of circulating IgG autoantibodies. These autoantibodies, which have been shown to be pathogenic, bind to complexes on the keratinocyte cell surface and have been utilized to establish that these complexes contain components found in cell adhesion junctions. Although the stimulus for autoantibody production is unknown, proposed mechanisms to explain the disease pathophysiology include proteinase activation, complement activation, and direct interference of cell adhesion junction assembly by autoantibodies. Although pemphigus vulgaris was commonly fatal prior to the availability of glucocorticosteroids, the prognosis has improved dramatically since their introduction. Immunosuppressive agents have also been successfully employed to treat patients with more severe disease. PMID- 2249361 TI - Pemphigoid. Bullous and cicatricial. AB - Bullous pemphigoid is a blistering disease of the elderly that often is self limited. It is apparently caused by autoantibodies against antigens of the basal cell hemidesmosome. There is apparently more than one antigen, but the most significant has a molecular weight of about 230 kD and the second most frequently detected antigen has a lower molecular weight of about 166 to 180 kD. The subepidermal blister presumably is produced by autoantibody binding along the basement membrane zone, followed by a complex series of inflammatory events. Conservative use of oral and topical corticosteroids often is sufficient to control the disease. Cicatricial pemphigoid has similar immunologic features, but it is not known if the same antigens are immunogenic in this disease. Scarring of mucosal surfaces due to recurrent blistering can result in blindness, asphyxiation, and esophageal stenosis. Treatment is more difficult and often requires short-term, intensive immunosuppression with cyclophosphamide. PMID- 2249362 TI - Acquired epidermolysis bullosa. A bullous disease associated with autoimmunity to type VII (anchoring fibril) collagen. AB - Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal blistering disease of the skin in which one finds tissue-bound and circulating antibodies are bound to type VII collagen. Although not definitely proven, current evidence strongly suggests that EBA is an autoimmune disease. The true etiology or initiating event that triggers EBA has not been identified. PMID- 2249364 TI - Psoriasis. Leukocytes and cytokines. AB - Elements of the immune system must take their place alongside other potential mechanisms of psoriasis, such as psoriatic epidermal keratinocytic hyperproliferation, endothelial cell and fibroblast activation and proliferation, abnormal lipid regulation, and transmembrane signalling abnormalities. These data provide support for the concept that cellular immunologic processes are active in a manner that further promotes the patho-physiologic events observed in psoriasis. Thus, therapies useful for psoriasis may have activity on immunologic processes in addition to more traditional mechanistic conceptions of effects on keratinocyte proliferation or other constitutive cell activity. As depicted in Figure 1, UV light, steroids, cyclosporine, and tars have potent inhibitory effects on antigen-presenting cells as well as on T cells. Methotrexate and azathioprine both have immunosuppressive activities, and even retinoids have complex immunomodulatory activity in addition to their ability to alter keratinocyte differentiation (or responsiveness to lymphokines). Cyclosporine has potent effects on T cells after they encounter activating signals such as foreign antigens or autoantigens. Although the T cell actually can become partially activated in the presence of cyclosporine, the drug interferes with the ability of the activated T cell to synthesize and secrete lymphokines (such as IL-2 or gamma-interferon) critical for the initiation and amplification of immune responses to a particular antigen. Although interruption of a single critical pathway improves psoriasis, it is likely that the most effective medications for psoriasis have actions on more than one cell type important in the pathogenesis of the lesion. PMID- 2249363 TI - Herpes gestationis. AB - Herpes gestationis is a rare, pruritic, non-viral, polymorphic dermatosis of pregnancy and the puerperium. Lesions in this disorder are typified by pruritic vesiculobullae and urticarial plaques distributed over the abdomen, buttocks, and extremities. HG tends to recur in subsequent pregnancies and often flares at delivery. Although HG usually resolves within weeks to months of parturition, patients may experience a flare of disease after taking oral contraceptives or in response to other hormonal stimuli. Biopsy specimens from lesional sites demonstrate characteristic but not diagnostic features. The diagnosis of HG is based not only on its clinical and histopathologic features but also on the demonstration of linear deposits of C3 within the epidermal BMZ of the patient's normal-appearing, perilesional skin. These deposits signify the presence of a low titer anti-epidermal BMZ IgG antibody that binds a precise antigen within the lamina lucida, avidly fixes complement, and presumably produces an inflammatory reaction responsible for tissue damage and blister formation. It is critical to study patient skin for evidence of C3 in situ because some patients with HG show no evidence of an antiepidermal BMZ antibody in routine indirect immunofluorescence microscopy and some remain negative in specialized complement fixation studies. An additional laboratory finding in patients with HG is their increased frequency of the HLA-B8 and HLA-DR3 haplotypes as well as the HLA-DR3, DR4 paired haplotype. Herpes gestationis has clinical, histologic, and immunopathologic features that resemble selected aspects of BP. Although many dissimilarities exist between these diseases, studies have shown that antiepidermal BMZ antibodies in patients with HG and BP recognize related or identical antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249365 TI - Immunologic aspects of atopic dermatitis. AB - The immunology of atopic dermatitis is complex, multilayered, and multifaceted. In one realm are the IgE-mediated, type I hypersensitivity reactions that can be elicited in at least 80% of patients. A second realm is that associated with cell mediated immunity and delayed-type hypersensitivity (type IV) reactions. Scattered between these immunologic paradigms are the various splinters: immune complex abnormalities, putative late-phase reactions, and cutaneous basophil hypersensitivity. The inflammatory lesion of atopic dermatitis probably is a composite of the many model reactions that investigators have glimpsed but never resolved into a reasonable concept. PMID- 2249366 TI - Pathogenesis of anti-Ro/SS-A autoantibody-associated cutaneous lupus erythematosus. AB - Patients with several clinically distinctive types of cutaneous LE (e.g., SCLE, neonatal LE) frequently are found to have autoantibodies to the Ro RNP particle present in their circulation. Some studies suggest that these antibodies might be capable of directly triggering the type of histopathologic changes seen in SCLE and neonatal LE through immunologic effector mechanisms such as ADCC. Other investigative results, however, are not compatible with this hypothesis. A better understanding of the molecular configuration of the Ro small cellular RNP particle, the factors that regulate the expression of this complex autoantigen system in epidermal keratinocytes, and the overall pathogenetic potential of the Ro autoimmune response should provide some insight into this seeming paradox. PMID- 2249367 TI - Dermatitis herpetiformis. AB - The state of our understanding of the pathogenesis of DH relies on the integration of several key characteristics: (1) a high frequency of the HLA antigens HLA-B8, HLA-DR3, and HLA-DQw2, (2) an associated GSE, (3) the resolution of both the skin lesions and gut abnormalities in response to a gluten-free diet, and (4) the presence of granular deposits of IgA in normal and perilesional skin. The role of the HLA class II antigens expressed in patients with DH most likely relates to the afferent or initiating arm of the immune system. The association of the HLA-A1, -B8, -DR3, -DQw2 haplotype with Sjogren's syndrome, chronic hepatitis, Graves' disease, and other presumably immunologically mediated diseases, as well as the evidence that some normal HLA-B8, -DR3 individuals have an abnormal in vitro lymphocyte response to wheat protein and mitogens and have abnormal Fc-IgG receptor-mediated functions, suggests that this HLA haplotype or genes linked closely to it may confer a generalized state of immune susceptibility on its carrier, the exact phenotypic expression of which depends on other genetic or environmental determinants. It also is clear, from the association of DH with GSE and the ability to control the cutaneous manifestations of DH with a gluten-free diet, that the gut disease is a critical factor in the pathogenesis of DH. Several pathogenetic theories about the origin of the cutaneous IgA deposits in DH have been proposed, one of which states that the IgA is produced in the gut mucosa as a response to a dietary antigen or gut epithelial antigen and then cross-reacts with the skin of patients with DH. A second hypothesis is that the IgA produced in the gut binds to an antigen and is deposited in skin as an antigen-antibody complex. Finally, it could be that the gut mucosal abnormality simply allows an unknown antigen access to the central immune system where an IgA antibody is produced that binds to skin. The failure to detect circulating IgA anti-basement membrane zone antibodies in patients with DH suggests that either the structures to which the IgA binds are not present in normal skin without DH, that IgA cannot bind to these structures in vitro, or that the circulating IgA is too scant for detection with conventional methods. Finally, it must be considered that the IgA deposited in DH skin may bind as a result of non-antigen-antibody interactions that cannot be duplicated in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249368 TI - Preoperative evaluation of the surgical patient. AB - Both the patient and the surgeon benefit from a complete and thorough preoperative evaluation. Such evaluation may permit the surgeon to identify surgical candidates at risk for problems, institute corrective measures, and thus reduce surgical complications. Time spent by the surgeon in preoperative patient education often yields increased patient confidence and enables patients to make informed decisions about their own care. The overall result is that surgical care becomes more efficient, more pleasant for the patient, and less stressful for the surgeon. PMID- 2249369 TI - Consensus for a core curriculum in clinical pharmacology for medical students. PMID- 2249370 TI - A core curriculum for medical students in clinical pharmacology and therapeutics. The Council for Medical Student Education in Clinical Pharmacology and Therapeutics. PMID- 2249371 TI - A perspective on the American Board of Clinical Pharmacology, Inc. PMID- 2249372 TI - Extrahepatic metabolism of morphine occurs in humans. AB - The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half-life was 92 +/- 9 minutes, total body clearance was 1260 ml.min-1, and the hepatic extraction ratio was 0.65 +/- 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney. PMID- 2249373 TI - The contribution of N-hydroxylation and acetylation to dapsone pharmacokinetics in normal subjects. AB - The relative importance of N-hydroxylation and acetylation of dapsone to the oral clearance of dapsone (100 mg) was investigated in seven healthy volunteers. Plasma dapsone and monoacetyldapsone concentrations rose rapidly with subsequent similar monoexponential elimination. The oral clearance of dapsone was low (33 +/ 14 ml/min), with a threefold variability. Four subjects were identified as fast acetylators; however, differences in acetylation did not explain the variability in oral clearance. The cumulative urinary recoveries of dapsone and its hydroxylamine were approximately 20% of the dose. The formation clearance of hydroxylamine, which exhibited a tenfold intersubject variability, was closely associated with the oral clearance of dapsone (r = 0.96). Thus, the formation of the hydroxylamine is more important than acetylation in determining dapsone's intersubject variability in oral clearance. Variation in N-hydroxylation may have clinical consequences, because the hydroxylamine is considered to be important in dapsone-mediated toxicity. PMID- 2249374 TI - Xipamide disposition in liver cirrhosis. AB - The pharmacokinetics of the sulfonamide-type diuretic xipamide was studied in patients with liver cirrhosis and ascites and compared with healthy control subjects. After oral administration of 40 mg xipamide, the diuretic was rapidly distributed in the blood and the ascites. The ratio of the area under the concentration-time curve (AUC) of plasma and ascitic fluid was 7:2, as was the protein content in the respective compartments. The AUC in plasma of cirrhotic patients was significantly greater than in control subjects (p less than 0.001). The most striking finding was the increase of the amount (Ae) of parent drug and main metabolite excreted into the urine (p less than 0.001). The renal clearance of xipamide was only moderately reduced in patients with liver cirrhosis. Both AUC and Ae were positively correlated to the plasma concentration of direct bilirubin of the patients (p less than 0.05). We concluded that nonrenal drug clearance in patients with liver cirrhosis was reduced as a result of the blockade of hepatobiliary excretion during cholestatic conditions. PMID- 2249375 TI - The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans. AB - In this clinical investigation, four groups of subjects (eight young women and eight young men [age range, 18 to 25 years], and eight elderly women and eight elderly men [greater than 60 years of age]) received single oral doses (400 mg) of racemic mephobarbital. The apparent total body clearance of R-mephobarbital was much greater and the elimination half-life was much shorter in the young men compared with the other three groups. This enantiomer displayed an age-dependent gender effect and a gender-dependent age effect in its metabolism. The apparent total body clearance of the S-enantiomer was much lower than that of the R enantiomer in all subjects and did not differ between subject groups, although the elimination half-life was slightly but significantly shorter in young males. A consequence of these enantiomeric differences was an apparently enhanced stereoselectivity in the metabolism of mephobarbital in young men. These substantial influences of age and gender on the stereoselective disposition of mephobarbital are consistent with recent findings concerning the expression and regulation of cytochrome P450 enzymes. PMID- 2249376 TI - Disposition of nicotine and eight metabolites in smokers and nonsmokers: identification in smokers of two metabolites that are longer lived than cotinine. AB - The disposition of a single intravenous dose of 14C-nicotine was investigated in six cigarette smokers and six nonsmokers. Plasma and urinary elimination of both nicotine and cotinine was faster in smokers than in nonsmokers. In the urine of both smokers and nonsmokers, we identified nicotine and eight metabolites, including two new metabolites: metabolite A (3-hydroxycotinine glucuronide) and metabolite G (demethylcotinine delta 2',3'-enamine). Metabolites A and G were of particular interest because, in smokers, they both persisted longer than cotinine. This property renders them more sensitive than cotinine as potential indicators of passive exposure to cigarette smoke. PMID- 2249377 TI - Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate after single oral doses of each compound in healthy volunteers. AB - The tolerance, pharmacokinetics, and pharmacodynamics of adinazolam and N desmethyladinazolam (NDMAD) were assessed after single oral doses of 10, 30, and 50 mg adinazolam mesylate, NDMAD mesylate, and placebo. Within doses, six healthy male volunteers received these treatments in a double-blind crossover design. No clinically significant changes were observed in blood pressure, pulse, respiration, or clinical laboratory test results. Untoward effects were typical of benzodiazepines. Adinazolam and NDMAD kinetics were dose independent. Greater than 95% of the adinazolam dose was metabolized to NDMAD. Adinazolam and NDMAD mesylate produced dose-related increases in uric acid clearance and decreases in plasma uric acid. Both adinazolam and NDMAD mesylate administration resulted in dose-related sedation and decrements in psychomotor performance. Within doses, decrements produced by adinazolam and NDMAD were quantitatively similar. These results suggest that both adinazolam and NDMAD possess uricosuric activity and support the hypothesis that NDMAD primarily mediates benzodiazepine-like effects of adinazolam mesylate. PMID- 2249378 TI - Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients. AB - The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure ( 12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group. PMID- 2249380 TI - Refinements in flap reconstruction. PMID- 2249381 TI - Flap refinements: logs into harpsichords. PMID- 2249379 TI - Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. AB - The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment. PMID- 2249382 TI - Aesthetic refinements in use of forehead for nasal reconstruction: the paramedian forehead flap. AB - Historically, surgeons have avoided use of the forehead for nose reconstruction because they felt larger areas of tissue were required. As plastic surgery has evolved to achieve successful replacement of major nasal defects, the paramedian forehead flap has been refined as the best alternative. Judicious use of central forehead tissue will provide sufficient skin of excellent tint to allow total repair. Scars are almost always unobtrusive. The forehead flap covers fabricated composite flaps of intravasal lining and primary cartilage grafts that create the subsurface architecture of the external nose. The result is a nose with correct shape and color that appears normal. PMID- 2249383 TI - Lip reconstruction with motor and sensory innervated composite flaps. AB - Among the most elegant of recent flap refinements are innervated composite skin muscle-mucosal flaps that restore the oral sphincter and carry both motor and sensory nerves. These flaps are based on the orbicularis oris, depressor anguli oris, and levator anguli oris perioral muscles of facial expression. Each flap can be dissected in a manner that allows transfer of the muscle into the oral sphincteric ring while restoring lip form and preserves the motor and sensory innervation. Each flap can be designed to carry skin and mucosa as needed for cover, lining, and vermilion reconstruction. Choice is determined by the specific anatomic lip defects. The orbicularis oris flap is most useful for large central defects of either the upper or lower lip. The depressor anguli oris flap is most useful for lateral lower lip defects or total lower lip reconstruction with bilateral flaps. The levator anguli oris is most useful for upper lip lateral element defects or for total upper lip restoration with bilateral flaps and an Abbe flap philtral reconstruction. Innervated composite flaps demonstrate substantial advantages when compared with preceding methods because of the superior function conveyed by the sphincter reconstruction and preserved motor and sensory nerve innervation. PMID- 2249384 TI - Flaps for cleft lip and palate surgery. AB - The advantages of palate repair by double opposing Z-plasty include excellent access for complete mobilization of the palatal muscles, construction of an overlapping muscle sling, and avoidance of the growth-limiting horseshoe-type scars of the hard palate that result from lateral relaxing incisions or pushback procedures. The excellent speech that results seems to justify use of the procedure. An Abbe flap designed to mimic the normal philtrum placed over an interlacing orbicularis reconstruction that is well supported superiorly can salvage a thin, scarred upper lip and improve its mobility. The lateral gingival flap provides excellent esthetic reconstruction of the cleft alveolus, secure cover over an alveolar bone graft, and ease closure of an anterior oronasal fistula. PMID- 2249385 TI - Surgical management of facial palsy. AB - Patients with facial palsy present with a multitude of different problems to which individual solutions must be carefully tailored. Although numerous surgical options exist, the results of reconstruction are rarely ideal. This article discusses different surgical procedures for reconstruction of the eye and mouth with special emphasis on the newer technique of microsurgical transfer of muscle tissue for reanimation. PMID- 2249386 TI - The use of free tissue transfer to restore facial contour. AB - Free tissue transfer offers two-stage augmentation of the facial soft tissues. Nevertheless, it is not unusual to require additional touch-up procedures. An accurate assessment of the preoperative facial deficit will allow for appropriate flap selection and predictable surgical results. PMID- 2249387 TI - Mandibular-facial reconstruction with segmentally split serratus anterior composite flaps. AB - Oncologic or traumatic head and neck defects with missing mandible, facial skin, and oral mucosa are especially well suited to reconstruction with a composite tissue unit, based on the subscapular-thoracodorsal vessels, that carries any combination of skin, bone, and muscle to restore vascularized skeletal structures, oral lining, and skin cover. The subscapular-thoracodorsal vascular pedicles supply segmentally split units of the lower serratus muscle and ribs on which it originates. Also, one or two skin paddles for cover and lining flaps are carried either by the cutaneous scapular and parascapular branches of the circumflex scapular vessels or by surgically split segments of the latissimus dorsi musculocutaneous flap. The composite flap can be designed in a variety of combinations to meet recipient defect needs and allow retained innervated segments of the component muscles in situ for preservation of donor motor function. The common subscapular-thoracodorsal vascular pedicle can be transferred either as a microvascular free flap or by pedicle transposition through a subpectoral-subplatysmal tunnel to the mandibular-facial defect. This versatile reconstructive unit illustrates many of the refinements of contemporary flap reconstructions. PMID- 2249388 TI - Refinements in free flaps for head and neck reconstruction. AB - The decade of adolescence of microsurgical techniques of head and neck reconstruction has led to a further clarification of the indications and methods for microsurgical reconstruction of head and neck defects. A review of the defects and the variety of flaps available for reconstruction leads to an increased understanding of the advantages and disadvantages of these various methods. When assessing a defect in the head and neck for microsurgical reconstruction, the surgeon should consider the various advantages of the flap to be used and weigh them against the disadvantages. The specialty has long since passed the point when one or two donor flaps could be considered to answer all of the reconstructive questions. We must now thoughtfully consider all the available options before settling on a course of treatment. PMID- 2249389 TI - Segmentally split pectoral girdle muscle flaps for chest-wall and intrathoracic reconstruction. AB - The latissimus dorsi, pectoralis major, and serratus anterior provide the principal flaps for major chest-wall and intrathoracic reconstructions. Each of these muscles shows a philogenetically preserved internal metamerism that is expressed by a segmental morphology and neurovascular supply. This segmental anatomy creates multiple independent subunits in each muscle that can be surgically split and independently used. Surgically splitting these muscles permits flap refinements such as creating two flaps from one donor muscle and leaving independent subunits in situ to preserve donor motor function after flap transfer. The latissimus dorsi has a consistent proximal bifurcation of its neurovascular supply into a medial and lateral branch that permits dividing the muscle or skin-muscle unit into two independent flaps. The pectoralis major has three segmental neurovascular subunits, the clavicular, the sternocostal, and the external. These can be surgically split and independently transferred on vascular pedicles from the thoracoacromial, internal mammary, and lateral thoracic vessels. This provides a substantial degree of donor motor preservation, as shown by the pectoralis V-Y myoplasty for mediastinal reconstruction. The serratus arterial has a highly segmental morphology with multiple subunits corresponding to each of the first nine costovertebral units; it also can be surgically split. The resultant upper and lower groups can be further subdivided if needed. These flaps provide useful intrathoracic reconstruction with a substantial degree of donor motor preservation. Such technical refinements substantially increase each flap's versatility and lessens the donor cost for thoracic reconstruction. PMID- 2249390 TI - Refinements in intrathoracic use of muscle flaps. AB - Intrathoracic infections associated with infection, leakage, or bleeding of the airway, lung parenchyma, esophagus, heart or great vessels is a life-threatening situation that luckily is infrequently seen. Failure to control these infections with the usual techniques can often be attributed to the presence of persistent pleural space, continuing empyema or bronchopleural fistula. Intrathoracic transposition of extrathoracic skeletal muscle in these situations offers an effective of management. Our experience has been possible because of the continued integrated effort with our thoracic surgical colleagues. We have found the team approach to work best and will continue to use it. PMID- 2249391 TI - Refinements in vaginal reconstruction using rectus abdominis flaps. AB - An improved method for vaginal reconstruction after pelvic exenteration or abdominal perineal resection is provided by the distally based rectus abdominis flap. This extended flap carries a skin paddle from the upper abdomen on the rectus abdominis muscle and deep inferior epigastric vascular pedicle. The skin paddle is inversely tubed to form a vaginal pouch and delivered transpelvically to the perineum. In addition to providing a vaginal reconstruction for sexual function, this reconstruction lessens pelvic wound complications in the exenteration patient by filling endopelvic dead space and revascularizing these frequently irradiated wounds. This method provides a neovagina with a single flap and does not involve additional donor sites in the thighs. Transpelvic passage from above not only fills endopelvic dead space better than thigh flaps, but also it allows retention of a vaginal cuff in supralevator resections. Another significant advantage of this reconstruction is its great reliability with minimal incidence of paddle loss. This flap design illustrates a type of flap refinement in which specific flaps can carry tissue from adjacent vascular territories because of anastomotic vessels between the two vascular territories, such as the vascular watershed between the deep inferior epigastric and superior epigastric vessels in this case. PMID- 2249392 TI - Fasciocutaneous flaps. AB - It is difficult to be objective about the fasciocutaneous system of flaps, whose development continues at an alarming speed. The references cited in this article, by no means comprehensive, are testimony to that. We have tried to be selective in our choice of reference, and anyone familiar with these references will have a good understanding of the fasciocutaneous system. These flaps have been recognized for less than 10 years, but their origins have been well based on an anatomical foundation. The revival in the anatomical basis of flaps, whether they be skin based, muscle based, or fascia based, is, we think, one of the most significant factors in the huge advance we have seen in reconstructive techniques in the last decade. To put reconstructive surgery in perspective, we see it in the following way: 1. Distant origins from ancient Egypt through Tagliacozzi to Dieffenbach. 2. The birth of modern reconstructive surgery, 1900 to 1930. 3. Skin flaps and the age of the tube, 1930 to 1960. 4. Anatomical renaissance; the axial skin flap and microsurgery. 5. The 1970s, decade of the muscle and musculocutaneous flaps. 6. The 1980s, decade of the fasciocutaneous flap. We repeat that to see our present efforts objectively is difficult. What is close to us seems more important, but as we progress further away from the origins of the fasciocutaneous flap, some aspects of these flaps will be seen as more important than others. The concept of including the fascia to produce a composite fascial skin flap is of fundamental importance. The discovery of these flaps is a milestone in reconstructive surgery. Our anatomical understanding of all flaps is also of paramount importance. Some of the individually described fasciocutaneous flaps will always remain best buys; some will be forgotten--and maybe even rediscovered. PMID- 2249393 TI - V-Y advancement flaps. Reusable flaps for pressure ulcer repair. AB - V-Y advancement modification of skin paddle design for the biceps femoris, tensor fascia lata, transverse lumbar, and gracilis flaps permits readvancement of each of these flaps for recurrent pressure ulcers. Our use of this refinement of these flaps over the past twelve years shows that up to two readvancements of each of these flaps can be done, thus preserving reconstructive options in a patient population prone to pressure ulcer recurrence. PMID- 2249394 TI - Refinements in lower extremity free flap surgery. AB - This chapter recommends numerous factors that are significant refinements in approach and execution of lower extremity free flaps. I encourage a clear conceptual separation between the two essential phases of successful reconstruction of problem wounds: wound preparation and flap transfer. I have found that antibiotic beads maintain the sterility of temporary bony dead space. Due emphasis should be given to preparation of the surgeon, patient, and wound, allowing a nonemergency approach to lower extremity free flap coverage. The surgeon needs to be familiar with a variety of flaps beyond the usual workhorse group. Also, attention should be paid to perioperative warmth and hydration, and vessels affected by posttraumatic vessel disease must be avoided. A positive attitude toward the use of vein grafts whenever necessary is important. I also favor careful planning of the exact size and shape of the flap and length of the vessels along with use of a widely spatulated technique of end-to-side anastomoses. PMID- 2249395 TI - Pulmonary problems in pregnancy. AB - Pregnant women with asthma and pulmonary infections should be treated essentially the same as nonpregnant women with similar disease severity. Definitive diagnosis and prompt treatment with heparin should be used for patients with pulmonary thromboembolism. PMID- 2249397 TI - The prevention of chronic airway obstruction. PMID- 2249396 TI - Update: management of asthma. PMID- 2249398 TI - Meconium aspiration syndrome. PMID- 2249399 TI - Thoracic empyema: causes, diagnosis, and treatment. AB - Thoracic empyema is a disease that has been recognized for centuries. The principles of management as stated by Hippocrates remain more or less unchanged. Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases. With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis. When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay. The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered. If the original infection is adequately treated, empyema rarely occurs. Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention. These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment. Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management. PMID- 2249400 TI - Differential diagnosis and management of chronic cough. PMID- 2249401 TI - Childhood pulmonary function following hyaline membrane disease. AB - Hyaline membrane disease per se is not associated with abnormal lung function or increased nonspecific airway reactivity in childhood or adulthood. Very-low-birth weight infants who survive almost routinely in neonatal ICUs are at risk, however, for developing airflow obstruction and having airway hyperreactivity as children, and for having recurrent bouts of wheezing, cough, and respiratory infections. Neonates who develop BPD have the greatest risk of abnormal pulmonary function as children. Continued research into the prevention of premature birth and into the causes of neonatal lung injury, combined with improvements in the neonatal ICU and follow-up treatment, will undoubtedly contribute to improvement in the clinical course of premature infants. PMID- 2249402 TI - Causes, diagnosis, and treatment of pharyngitis. AB - Pharyngitis is a common disease of the respiratory tract that can be caused by several different viruses and bacterial organisms. Clinically speaking, the most important causative agent is group A streptococcus (Streptococcus pyogenes). Although rare, postpharyngitis complications arise as a result of disease caused almost exclusively by group A streptococcus. Because group A streptococcal pharyngitis usually responds well to antimicrobial treatment, it is important to diagnose it. Penicillin, erythromycin, and peroral first-generation cephalosporins have been documented to be effective. In addition to group A streptococcus, C. pneumoniae and M. pneumoniae have also been detected in patients with pharyngitis. The possibility of diagnosing these organisms is limited at the present. Clinical surveys are still needed, moreover, to evaluate the effect of antimicrobial treatment on the disease caused by these organisms. Although routine viral diagnostic methods do not help primary care physicians in treating patients with pharyngitis, information on bacteria and viruses in the immediate environment could prove to be of great help in daily clinical work. PMID- 2249403 TI - The adult respiratory distress syndrome. AB - The adult respiratory distress syndrome remains an enigmatic disorder with a high mortality rate, although it can sometimes be managed effectively. Recognizing the conditions with which it is associated is the first step in preventing its occurrence. Decreasing the risk factors of developing ARDS remains the fundamental goal of initial management. Once the syndrome has developed in a particular patient, the clinician's goals in management are to stabilize the patient, avoid further insults, maximize the support therapies available, and be cognizant of and avoid the potential adverse effects of these supportive therapies. PMID- 2249404 TI - Bacterial translocation from the gastrointestinal tract. PMID- 2249405 TI - Using a "lifestyle" perspective to understand toothbrushing behaviour in Scottish schoolchildren. AB - Using data from a wider survey of health related behaviour in 4,935 Lothian schoolchildren, 11, 13, and 15 yr old, this paper analysed toothbrushing frequency and its relation to "lifestyle" factors. Analysis of the results showed that girls brush more frequently than boys and that children with higher social class background brushed more frequently than children with low social class background. Further toothbrushing frequency was significantly related to the subjects' health perception, smoking and drinking habits, eating habits, bedtimes, and video-watching. Moreover, all these lifestyle factors were inter related. The paper reinforced the concept of lifestyle as a meaningful descriptive term. The results demonstrated that the bivariate associations are pieces in a more complex mosaic. Toothbrushing thus seems to be an integrated part of a child's lifestyle and should be regarded as such in future health promotion efforts. PMID- 2249406 TI - Combined fluoride therapies. A 6-year double-blind school-based preventive dentistry study in Inverness, Scotland. AB - A 6-yr double-blind study was undertaken to compare the caries inhibiting effectiveness of (a) 1 mgF- tablets (daily at school) plus fortnightly rinsing at school with 1000 ppmF-; (b) 1 mgF- tablets plus placebo rinsing; and (c) placebo tablets plus 1000 ppmF- rinsing. Participants were aged 4.5-5 yr at outset of the trial. At baseline, and annually thereafter, clinical caries and bitewing X-ray examinations were undertaken, hence ethical approval for a negative control was not feasible. Fissure sealant presence was also recorded. Initially, 192 children from predominantly low socio-economic backgrounds were enrolled, and baseline analyses showed no significant differences between groups with respect to primary caries prevalence. After 6 yr, 112 children remained, by which time no significant differences were noted between DMFT and DMFS values for those in the active tablet/active rinse group, as compared to those in the placebo tablet/active rinse group. However, in relation to both indices, in permanent first molars, the effectiveness of the active tablet/placebo rinse regime appeared to be significantly poorer than the placebo tablet/active rinse programme. For the active tablet/active rinse group, the DMFT difference was significantly less than the active tablet/placebo rinse group (37.9%), although for the DMFS difference, significance was not achieved. Similar trends were noted when DMFT and DMFS values for all permanent teeth were considered. The occlusal caries prevalence in permanent first molars followed the DMFT pattern, but differences between combined tablet/rinsing children and tablet-only children could be ascribed solely to the effectiveness of sealant presence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249407 TI - Dental caries, mutans streptococci, lactobacilli, and saliva secretion rate in adults. AB - In 718 Swedish patients, equally divided into four age groups (19-25, 26-45, 46 60, greater than 60 yr), salivary levels of mutans streptococci and lactobacilli, saliva secretion rate, and DMFS were registered. No significant differences were found between the various age groups either in salivary factors or in caries (D). Number of missing (M) and filled (F) surfaces increased with age. Prevalence of root caries, which increased with age, was significantly correlated to number of exposed root surfaces independent of age. Of the total study group, 50% had greater than or equal to 10(6) mutans streptococci and 40% had greater than or equal to 10(5) lactobacilli per mL saliva. Three percent had a saliva secretion rate of less than or equal to 0.5 mL/min. Correlation analyses showed that both mutans streptococci and lactobacilli significantly correlated to the caries prevalence but the r-value never exceeded 0.34. PMID- 2249408 TI - Prevalence of malocclusion and need for orthodontic treatment in Saudi Arabia. AB - The prevalence of different malocclusion features was investigated in 500 14-yr old male Saudi Arabian children, using a modification of the registration method described by Bjork et al. (3). Most of the children were in dental stage DS4 (all permanent teeth anterior to the first molars erupted). Totally 62.4% of the children had one or more malocclusion features related to dentition, occlusion, or space. The treatment need was evaluated according to the guidelines used in the Norwegian Health Service. About 40% were found to need treatment with fixed appliances, and for 33% extraction of permanent teeth would be part of the treatment. Only about 2.5% would benefit from treatment with simple removable appliances. PMID- 2249409 TI - Longitudinal study of accuracy of clinical examination for detection of permanent tooth aplasia. AB - It was the aim of the present investigation to evaluate the accuracy of clinical examination for the detection of permanent tooth aplasia in the 3rd/4th grade and again 1 yr later and to record the number of children initiating orthodontic treatment in the interval between the two examinations. The validating criterion for tooth aplasia was a panoramic radiograph taken in a routine procedure. 628 children participated in the study. The clinical examinations were performed without knowledge of the radiographic evidence. During the examination children exhibiting symptoms of permanent tooth aplasia were selected for radiography. At both occasions clinical examination was very sensitive for the detection of children with aplasia of permanent incisors (nosological sensitivity = 1.00). It was, however, less sensitive for the detection of children with premolar aplasia (nosological sensitivity = 0.22 at both examinations). The nosological specificity for identification of children without aplasia of incisors and premolars was more than 0.90 at both examinations. Twenty-two children had started orthodontic treatment in the timespan between the two clinical examinations, but only three on the basis of observations on their radiographs alone (aplasia of permanent teeth). The present clinical method would have selected two of these children, thus in only one child postponing panorama screening might have affected treatment prognosis. Between the two examinations all permanent teeth mesial to the permanent second molars had erupted in 181 children who might therefore totally avoid screening radiography. PMID- 2249410 TI - Patients' retrospective preference for extraction of asymptomatic third molars. AB - The purpose of this study was to determine the personal utility of asymptomatic third molar removal in military patients. From 1 to 30 days (mean = 7.4) after the extraction of one or more third molars, 100 returning patients (all male, mean age = 20.1) were asked to respond to hypothetical questions concerning the extraction of asymptomatic third molars. If the likelihood of third molars ever having to be removed was given as 10%, 50%, and 100%, then 45%, 61%, and 88% of responses, respectively, showed preference for immediate extraction. When respondents chose to delay treatment until there was a problem, no likelihood group would tolerate more than 2.77 additional days of post-extraction pain before changing their preference to immediate extraction. 87% of respondents preferred extractions prior to a deployment which would make treatment delivery difficult, and 89% prior to becoming a civilian at which time treatment might no longer be free. The results indicate general acceptance of the strategy of prophylactic third molar removal among a sample of military patients who have undergone pre-treatment counseling and the surgical procedure. A question remains as to the personal utility that might be measured prior to surgery. PMID- 2249411 TI - Dental fear and pain: effect on patient's perception of the dentist. AB - A questionnaire was developed including the Dental Anxiety Scale (DAS) and the Dental Beliefs Survey (DBS) as subscales to examine the epidemiology of dental fear and dental beliefs in Germany. The survey was administered before treatment to a sample of 474 dental patients. Of the respondents 56% were female. The mean age was 34.3 yr (SD 12.4 yr). The mean DAS score was 8.6 (SD 3.7). Mean DBS score ranged from 1.73 to 2.75 for single items. The correlation between DAS and DBS scores was highly significant (rs = 0.39, P less than 0.001). Absence or presence of dental pain revealed significant differences for DAS and DBS scores (P less than 0.001). Both tests are valid screening forms for the German linguistic context and easy to implement in daily dental routine. PMID- 2249412 TI - Dental anxiety: a comparison of dentate and edentulous subjects. AB - Dental anxiety was measured in a representative, nationwide sample consisting of both dentate and edentulous subjects. Comparison of the mean scores of both groups shows that the edentulous sample is neither more nor less anxious about dental treatment than the dentate sample. The distribution of dental anxiety in edentulous subjects, however, differs considerably from that of the dentate group. Complete denture wearers are both more often dentally phobic and more often free from any anxiety than subjects still having at least part of their natural dentition. PMID- 2249413 TI - Prevalence of dental anxiety and fear in children in Singapore. AB - 505 primary school children in Singapore aged 10-14 were surveyed regarding fear of the dentist. Sixty-eight children were classified as having high fear, giving a sex and race adjusted population prevalence rate of 177 fearful children per 1000 population. Females were 2.64 times more fearful than males. There were no significant racial differences in the prevalence rate. Children with high state anxiety are almost three times as likely to report dental fear as those with low state anxiety. Children with trait anxiety scores above the population mean were just as likely as those reporting below the mean to be fearful. Access to dental care is an important intervening variable in dental fear. PMID- 2249414 TI - Differences in oral health status between institutionalized and non institutionalized older adults. AB - Differences in oral health status between independent and institutionalized adults have been difficult to interpret because the latter population is typically older and has a higher proportion of women, confounding any association between institutionalization and disease levels. We undertook an analysis of oral disease amongst institutionalized (n = 149) and non-institutionalized (n = 246) samples of older adults randomly selected from the population in East York, Ontario. When the confounding effects of age and gender were controlled by constructing 67 matched pairs, institutionalized people were more than twice as likely to be edentulous (OR = 2.17, 95% CI = 1.09-4.29). This association was confirmed using data from all subjects in a logistic regression model. Analysis of covariance of data from dentate subjects revealed that the institutionalized seniors had fewer filled teeth (P less than 0.05, controlling for age and sex), but there were no statistically significant differences in the number of teeth which were missing, decayed, or requiring extraction. These findings suggest that antecedent, sociodemographic factors prior to institutionalization are responsible for the higher probability of oral disease in this group of older adults. PMID- 2249415 TI - Relationship between dental caries and vegetarian and non-vegetarian diets. PMID- 2249416 TI - What are computers and models good for? Pros and cons. PMID- 2249418 TI - A multicompartment model for open-loop control of glucose in insulin-dependent diabetics. AB - This paper describes a model that has been developed for individually adjusted therapy management in insulin-dependent diabetics. The multicompartment model considers all relevant aspects of glucose kinetics and its dependence on insulin. The structure of the model reflects that of the physiological system. Its parameters can be classified into (a) general parameters that are independent of the individual, (b) classifying parameters that are related systematically to the individual, and (c) distinguishing parameters. Classifying parameters allow a very convenient adjustment to relevant features of the individual like sex, age, body weight and length. The model can be employed in open-loop control for the calculation of insulin dosages. It allows the prediction of the system's behaviour as well as the consideration of predictable disturbance variables, e.g. food intake and physical exercise. PMID- 2249417 TI - Information technology and computer-based decision support in diabetic management. AB - This paper describes the application of computer-based techniques within an intelligent, knowledge-based framework to the management of diabetes. The objectives are to structure data collection and storage so that the relevant patient-specific data are collected and made accessible as needed, and to provide clinical decision support on either a day-by-day or longer timescale as appropriate; these objectives relating to both hospital clinic and general practice. For longer-term management, a prototype rule set (greater than 500 rules) has been developed (coded in Sigma PROLOG), validated and tested on patient data. The data collection programs (written in SCULPTOR) to feed the ruleset have been tested in the hospital clinic and compared with the resident data collection system for usability, and impact on the running of the clinic. Links between the data collection programs and the ruleset program have been written and tested. The computer system will also incorporate a module, combining knowledge-based advisory system and glucose/insulin model as patient simulator, that can be tested as a potential decision aid for adjusting insulin dosage on a daily basis. PMID- 2249419 TI - Computer-assisted diabetic management: a complex approach. AB - This paper describes the architecture of, and the main reasoning methods involved in, a computer system developed to assist in diabetic management. The system integrates (i) a database module used for blood glucose monitoring, (ii) an interpreter module used to analyse the adequacy of diet and insulin treatment for diabetics, and (iii) an advisory module suggesting alterations in diet and/or insulin regimen in order to improve glycaemic control. The analysis of blood glucose profiles and hypoglycaemic episodes, as well as the suggestions for altered diet and insulin therapy, are based on qualitative and quantitative models of insulin effect and carbohydrate absorption using meal-time related glucose balance and distance from the preselected target (DFT) glucose values as focal concepts in the reasoning process. During the sequence of consultations with the system, a dynamic model of carbohydrate metabolism is gradually adjusted in order to constitute an appropriate simulation for the specific patient. This model is used to confirm the suggestions made by the ADVISOR program and to assist the health care professional in selecting the best control action by predicting the blood glucose profiles resulting from alternative control policies. PMID- 2249420 TI - Computer-aided systems in the management of type I diabetes: the application of a model-based strategy. AB - One approach of improving metabolic control in type I diabetic patients is the application of computer-aided procedures aimed at supporting the decision on optimal therapeutic regimens. To accomplish this, a complex strategy was developed which in an individual patient permits (1) the evaluation of metabolic data by means of statistical and graphical methods, and (2) the prediction of the outcome in feedback and in non-feedback-controlled insulin therapy. The latter is realized by means of simulation, employing a structured model of the glucose insulin control system where the model parameters can either be identified individually or be taken at random. The practical applicability was validated in C-peptide-negative type I diabetic patients who were on intensified insulin injection therapy. The comparison between theoretical predictions and daily glycaemic profiles measured by the patients under ambulatory conditions showed close correspondence which justifies the application of this method as a clinical decision support. PMID- 2249421 TI - The influence of different generations of computer algorithms on diabetes control. AB - With all control schedules, the management of diabetes is possible using Skyler's algorithm. In general, those control algorithms which do not allow the individual adaptation to changing conditions lead to overinsulinisation. So-called meal related algorithms do usually minimise the fluctuations in blood sugar. The introduction of self-adapting algorithms, detecting peripheral insulin resistance, may further improve metabolic diabetes control. PMID- 2249422 TI - The use of models in the self-management of insulin-dependent diabetes mellitus. AB - Open-loop control of blood glucose for insulin-dependent diabetes is a biomedical control problem amenable to engineering analysis even when the control decisions and actions are made manually. The fundamental components of any control system include a model of the system being controlled, and a strategy for controlling the system using the model as a guide. Most models presently used in diabetes management limit the flexibility of diabetic control strategies because of technical shortcomings. Most control strategies limit their intervention to insulin adjustments, while food, exercise, and the timing of all metabolic inputs could be manipulated by the patient if suitably powerful, individualized, physiological models could provide the appropriate guidance. The pieces of such a comprehensive model are detailed, and the clinical benefits of the flexible control strategy made possible by the model are described. PMID- 2249423 TI - Estimation of beta-cell secretion and insulin hepatic extraction by the minimal modelling technique. AB - Mathematical models are a necessary tool to quantify physiological processes the direct measurement of which is not possible. Pancreatic beta-cell and liver are respectively the secreting and the major degrading site of insulin. To provide a quantitative description of these processes, we have conceived a method which exploits two minimal mathematical models. By using one model the post-hepatic delivery of insulin into the systemic circulation, IDRT(t), is estimated; the other model yields CPST(t), i.e. the secretion rate of C-peptide, which is equimolarly released by the beta-cell with insulin, but is not degraded by the liver. The estimated C-peptide flow rate into plasma is thus representative of that of pre-hepatic insulin. The difference between CPST(t) and IDRT(t) gives the insulin extraction by the hepatocytes. The parameters of the models are estimated in every single subject from the analysis of glucose, insulin, and C-peptide concentration data measured after an intravenous glucose injection. As an example of its usefulness, the method has been applied in patients with liver cirrhosis and in obese non-diabetic subjects, with the purpose of elucidating which mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because mechanism is responsible for the peripheral dynamic hyperinsulinaemia characteristic of such metabolic states. Because of its relative non-invasiveness compared to other techniques this model based method should prove useful in several other clinical investigations. PMID- 2249424 TI - Experimental validation of a glucose-insulin control model to stimulate patterns in glucose turnover. AB - To verify a structured model of the glucose-insulin system, metabolic measurements were compared with model-based simulations in insulin-dependent diabetic dogs which had been previously identified in terms of model parameters. Glycaemia, glucosuria, plasma insulin, and the rates of appearance Ra and disappearance Rd of glucose (kinetics of double-labelled glucose, evaluated according to Steele's equation in its non-steady-state version) were observed under the following conditions, starting from normoglycaemia during glucose controlled insulin infusion (GCII): (I) insulin withdrawal, (II) insulin withdrawal and glucose infusion, (III) constant i.v. infusion of glucose and insulin, (IV) glucose infusion during GCII. After fitting the patterns of glycaemia, simulations of the other state variables were accomplished, employing the individual model parameters, the preset experimental inputs, and the GCII control constants (test IV only). Under nearly all conditions, correspondence was excellent between measured and simulated data. There were, however, the following exceptions: incomplete representation by the model of kinetics in glucose utilisation after interruption of insulin supply, overestimation of glucosuria by the model in the presence of insulin. It is concluded that the model provides a reasonable representation of metabolic processes which are of importance in the treatment of insulin-dependent diabetes mellitus and that it might thus appropriately simulate the outcome of metabolic regimens. PMID- 2249425 TI - Computer models of albumin and haemoglobin glycation. AB - Two first-order mathematical models were developed to mimic the glycation of haemoglobin (H) and albumin (A). The total concentrations of A and H were assumed to be constant. The responses of the two models to varying blood glucose level were compared. The parameters of the haemoglobin model were not numerically estimated, only an informal fit was performed using clinical and published data. Nonlinear regression analysis was used to estimate the parameters of the albumin model. The level of glycated A (GA) was derived from the measured fructosamine level. Three diabetics were monitored daily for the level of fructosamine and blood glucose profile over a period of 10, 16 and 21 days, respectively. CONCLUSIONS: (1) The difference between GA and glycated H (GH) resulting from different elimination rates is decreased by the stratification of erythrocyte population. (2) Both GA and GH seem to have higher elimination rates than their nonglycated equivalents. PMID- 2249426 TI - Analysis of low density lipoprotein apheresis: post-treatment rebound using mathematical models. AB - Double membrane low density lipoprotein (LDL) apheresis (thermofiltration) was applied to treat six hyperlipidaemic patients and five controls 14 and 5 times, respectively, and post-treatment plasma LDL cholesterol (LDLc) concentration rebound was measured. To simulate the rebound, a nonlinear model (NLM) was developed. It consists of two compartments representing plasma and liver. LDLc uptake by the liver is described by receptor-independent and by receptor-mediated transport as controlled by the liver cholesterol concentration. NLM analysis of patient data resulted in pre-treatment fractional catabolic rate (FCR) for LDLc of 0.19 day-1 and the maximum FCR for LDLc of 0.26 day-1 on the 4th day. NLM showed that in patients and controls the post-treatment LDL synthesis rate rose by 6% to 15%. The steady-state (kinetic) version of this model was used to develop a formula describing the relationship between the FCR for LDLc and blood plasma LDLc concentration which agrees well with published data. PMID- 2249427 TI - Kinetic modelling as a tool for the design of a vascular bioartificial pancreas: feedback between modelling and experimental validation. AB - A bioartificial pancreas is a system which contains isolated islets of Langerhans protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to lymphocytes and immunoglobulins. However, it is necessary to design a device which performs as a closed-loop insulin delivery system, more specifically which rapidly responds to a change in the recipient's blood glucose concentration by an appropriate change in insulin release. We have designed a system intended to be connected as an arteriovenous shunt of the recipient; islets are placed between two flat ultrafiltration membranes, and blood circulates successively above the upper, and below the lower, membrane, in reverse direction. A complete kinetic model of glucose transfer from blood to the islet compartment, of insulin generation by the islets displaying a biphasic insulin pattern, and of insulin transfer into the bloodstream was described, and parameters were calculated on the basis of experimental data obtained when islets of Langerhans were perfused in vitro with a synthetic buffer. The resulting calculations indicated that both diffusional and convective transfers were involved in glucose and insulin mass transfer across the membrane, the contribution of diffusion being the most important. The geometry of the system was therefore modified in order to decrease the resistance to flow inside the blood channel. This should increase, at a given hydrostatic pressure, the blood flow rate, and thereby improve the diffusional transfer of insulin. This should also decrease the thrombogenicity of the device.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249428 TI - DIABETEX--a decision support system for therapy of type I diabetic patients. AB - DIABETEX is a knowledge-based, computer-supported consultation system for the therapy of type I diabetic out-patients. Three knowledge bases contain the medical and technical knowledge for treating either adults, adolescents or children by means of injections or by pumps. For the evaluation of the quality of the decision proposals three groups of patients were studied. The results obtained in test phase 1, i.e. the retrospective evaluation of DIABETEX decision proposals by the experts, and in test phase 2, i.e. the parallel work of DIABETEX and of an expert and the subsequent evaluation by experts, provide the basis for the further development and application of the system by non-expert diabetologists. PMID- 2249429 TI - A consultation system for insulin therapy. AB - This paper describes a computer system to advice on insulin therapy for diabetic in-patients. A mathematical model was developed to describe the effect of insulin on blood glucose (BG) level. The system uses an adaptive approach to analyse the response to an applied insulin dosage. It learns the patient's individual parameters. All conventional injection and insulin pump regimens are supported. The individualised model is used to predict BG level of the proposed insulin dosage. The system uses a generate-reject strategy to output optimum insulin therapy in terms of optimum BG. The predictive capability of the system was tested and it is able to predict BG with a precision of 2.5 mmol/l after 3 days and 6 days of insulin pump treatment and conventional injection therapy, respectively. PMID- 2249430 TI - DIABLOG: a simulation program of insulin-glucose dynamics for education of diabetics. AB - This paper presents a dialogue computer program, DIABLOG, for the education of diabetic patients with insulin therapy. Through mathematical modelling of glucose insulin dynamics this program is able to simulate glucose and insulin profiles of a 24 h period and display them graphically as curves. The subjects could vary the carbohydrate content of meals, the injection time and dose of short-acting and intermediate-acting insulin and could switch to insulin pump therapy. For a first evaluation 22 patients with insulin-dependent diabetes mellitus tested the program and their comments were recorded by a questionnaire. The results indicate a good acceptance of the program even by patients with no previous computer experience. Further suggestions by the patients will be discussed as well. PMID- 2249431 TI - Phases of functional, near-normoglycaemic insulin substitution: what are computers good for in the rehabilitation process in type I (insulin-dependent) diabetes mellitus? AB - We have divided the rehabilitation process in patients with insulin-dependent diabetes mellitus into the following four phases. The basic phase, the so-called 'phase 0', provides information about literature, different strategies of treatment and introduces the use of regular insulin as well as blood sugar self monitoring. During 'phase 1' (i.e. 'diabetes education common sense') all the initial information from 'phase 0' will be used practically and discussed in depth. After the patient's actual insulin need (U/24 h) has been estimated, initial algorithms for functional insulin use can be defined. And this is the turning point to 'phase 2' of the group rehabilitation process, the so-called education in functional insulin use. Initial algorithms should be understood as a preliminary answer to the patient's questions, 'What is my basal insulin need?', 'How much insulin do I need for a particular amount of carbohydrates?', and 'What is the hypothetical response of my blood glucose to a particular amount of insulin?'. These algorithms are going to be used and optimised now by the patient (under the supervision of the physician) during the so-called 'insulin games' (fasting or 24 h, experimental violation of traditional dietary rules, etc.) to demonstrate (1) how to influence actual glycaemia through immediate correction of blood sugar off blood sugar target (primary adjustment of insulin dosing), and (2) how to optimise algorithms for insulin use (secondary insulin adjustment) in future conditions of different insulin sensitivity. The 'phase 3' of individual teaching is an ongoing process of updating the patient's knowledge and practical skills.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249432 TI - A new software for initiating and optimising insulin treatment of out-patients. AB - Two computer programs were developed, program I to optimise insulin treatment using six injections per day, and program II to convert these insulin profiles into less frequent injections of mixtures of regular and NPH insulin. The first software in an HP 41 CV pocket computer uses iterative adjustments during the day and on subsequent days to determine the optimal timing and dosage of insulin. Six self-monitored glucose values at 3 h intervals, insulin doses, and the effects of insulin on plasma glucose are memorised for calculations. The calculated insulin doses were applied by Optipen as five s.c. injections of regular insulin and one bedside injection of NPH insulin. After 5 days the optimised individual insulin profiles with six daily injections were processed by program II. It applies the pharmacokinetics of regular and NPH insulin to make suggestions for a more conventional insulin therapy with one, two, three or four daily injections of regular insulin, NPH insulin, or varying mixtures of both insulins. The procedure was well tolerated in eight insulin-dependent diabetes mellitus out-patients. Insulin therapy with two or three injections, fitted by the second program and selected according to the quality score, produced plasma glucose profiles as satisfactory as those obtained with six injections. The system allows the fine tuning of insulin therapy to out-patients with their individual diets and physical activities. PMID- 2249433 TI - DIABETEX decision module 2--calculation of insulin dose proposals and situation recognition by means of classifiers. AB - Current research in the field of medical decision making tries to represent and to analyse complex, uncertain and complicated situations. The first version of DIABETEX, which is a decision support system for the treatment of diabetic out patients, accepts the challenge to overcome these difficulties. It includes a network of rules on the basis of known glucose-insulin relationships under different situations. The insulin dose for type I diabetic patients is suggested accordingly. In this, the application of special cybernetic methods offers the chance to overcome complexity, uncertainty, fuzzyness and incompleteness of data. Two methods of classification are presented to complete the DIABETEX decision unit: (1) the Bayes' classification is used in the calculation of insulin doses for type I diabetic patients on multiple subcutaneous insulin injections considering the basis-bolus concept; (2) fuzzy classification is employed in separating 'normal diabetic days' from days with information on special situations such as exercise, illness, menstruation on the one side, from stress, hypoglycaemia etc. on the other. PMID- 2249434 TI - Computer-aided system for diabetes care in Berlin, G.D.R. AB - In the Centre of Diabetes and Metabolic Disorders of Berlin, G.D.R., a computer aided care system has been used since 1974, aiming at relieving physicians and medical staff from routine tasks and rendering possible epidemiological research on an unselected diabetes population of a defined area. The basis of the system is the data bank on diabetics (DB), where at present data from approximately 55,000 patients are stored. DB is used as a diabetes register of Berlin. On the basis of standardised criteria of diagnosis and therapy of diabetes mellitus in our dispensary care system, DB facilitates representative epidemiological analyses of the diabetic population, e.g. prevalence, incidence, duration of diabetes, and modes of treatment. The availability of general data on the population or the selection of specified groups of patients serves the management of the care system. Also, it supports the computer-aided recall of type II diabetics, treated either with diet alone or with diet and oral drugs. In this way, the standardised evaluation of treatment strategies in large populations of diabetics is possible on the basis of uniform metabolic criteria (blood glucose plus urinary glucose). The system consists of a main computer in the data processing unit and of personal computers in the diabetes centre which can be used either individually or as terminals to the main computer. During 14 years of experience, the computer-aided out-patient care of type II diabetics has proved efficient in a big-city area with a large population. PMID- 2249435 TI - The deployment of visual attention in the intact field of hemineglect patients. AB - Patients with left hemispatial neglect after right hemisphere lesions and control patients with right hemisphere lesions were presented in the ipsilesional (i.e., intact) visual field with stimuli that could occupy left-right relative positions. The patients were required to discriminate between target stimuli and distractors by emitting go/no-go responses. Reaction times (RTs) and measures of sensitivity (d') and response bias (beta) were obtained. The within-subjects comparisons showed that neglect patients were faster in the right than the left relative position, whereas control patients were faster in the left than the right relative position. The between-subjects comparisons showed that neglect patients were faster than control patients in the right relative position but slower in the left relative position. These effects were due to changes in processing efficiency, as attested by the fact that the differences in response speed were accompanied by congruent differences in sensitivity, whereas no differences in response bias were found. The results were interpreted by assuming that neglect patients focus attention on the right relative position and, therefore, have a small attentional focus concentrated on that position. By contrast, control patients, like normal subjects, would distribute attention between the two possible stimulus positions and, therefore, allocate attention to a larger portion of the visual field. PMID- 2249436 TI - The continuum of deep/phonological alexia. AB - Two patients exhibited all the characteristics of deep alexia shortly following brain injury. Both subsequently recovered some reading abilities and evolved to show a pattern of oral reading consistent with phonological alexia. These findings suggest that deep alexia and phonological alexia share common underlying deficits that are mediated by common neurological systems. A two-deficit psycholinguistic model is presented to account for the apparent continuity between deep alexia and phonological alexia. PMID- 2249437 TI - Automatic memory processes in patients with dementia-Alzheimer's type (DAT). AB - We examined patients with Dementia-Alzheimer's Type, depression, and matched controls on tasks designed to compare automatic (monitoring frequency and modality) and effortful (free recall) processing of words and pictures. The results demonstrated that depressed patients performed poorly only when conditions required effortful processing, but DAT patients performed poorly under all conditions. There was almost no overlap in scores between DAT and elderly depressed patients on one of the measures of automatic processing suggesting that this measure may be clinically useful. The results suggest that automatic memory processes can be partially dissociated from effortful memory processes, but that both types of operations are impaired in DAT patients. PMID- 2249438 TI - Differential sensitivity to context in diencephalic and temporal lobe amnesia. AB - This study compares diencephalic and temporal lobe amnesics on a memory task in which the encoding of temporal context is essential for accurate performance. On trial 1 subjects were shown four pictures and asked to discriminate them from distractors one minute later. On the three subsequent trials the same procedure was used except that items previously used as distractors became targets and vice versa. The results showed that both groups performed close to ceiling on trial 1. On trials 2, 3, and 4, however, the diencephalic group showed poorer accuracy than the temporal lobe group. These results indicate that the diencephalic amnesics have greater difficulty encoding distinctive contexts across trials 2, 3, and 4 than do the temporal lobe group. Explanations of this difference are discussed briefly. PMID- 2249439 TI - Concurrent and sequential pattern discrimination learning by patients with Korsakoff amnesia. AB - Patients with Korsakoff's syndrome and alcoholic controls learned to discriminate sets of pairs of patterns presented concurrently, in order to test predictions based on monkeys' performance in similar tasks following medial temporal or diencephalic lesions. In Experiment 1 the subjects learned a 2-pair, a 6-pair and a 10-pair set; the Korsakoff group were impaired on the first and last, but not on the second set. In Experiment 2, the same subjects learned single pairs sequentially, and 2-pair and 8-pair sets concurrently. The effect of 2 types of feedback for correct responses (visual or non-visual) was also compared. The Korsakoff patients were markedly poorer than controls under all conditions; the type of feedback made little difference. In several respects the patients' impairment differed from what had been predicted from the animal experiments. PMID- 2249440 TI - Double dissociation between temporal and spatial pattern processing in patients with frontal and parietal damage. AB - One hundred and twenty nine patients affected by a cerebral lesion confined to a single lobe, underwent a battery of tests including the "Temporal Rule Induction" (TRI) and the Raven's "Coloured Progressive Matrices" (CPM). Frontal patients scored lower than any other group on TRI and parietal patients on CPM. This contrasting pattern of performance provides strong empirical support to the hypothesis that the frontal lobe is specifically involved in tasks that require a control on temporally ordered information whereas the parietal lobe is concerned with cognitive activities that imply visuo-spatial analysis. PMID- 2249441 TI - A multi-method investigation of individual differences in hemisphericity. AB - The construct of hemisphericity contends that some individuals process information analytically and others holistically, and that these individual differences reflect characteristic preferences or strategies for left- and right hemisphere processing, respectively. We investigated whether hemisphericity was related to personality variables, as measured by trait anxiety and the tendency to express versus inhibit emotions. Sixty six right-handed subjects completed personality measures and were tested on two occasions with multiple measures of hemisphericity, including dichotic listening, tachistoscopic emotion recognition, verbal ability and spatial ability. Although some of the hemisphericity measures exhibited moderate reliability, they generally did not correlate significantly with each other or with measures of personality. However, a composite hemisphericity index indicated that right hemisphericity was modestly correlated with the tendency to express emotions and left hemisphericity with the tendency to inhibit emotions. We discuss some reasons for the failure to find either construct or predictive validity for hemisphericity. PMID- 2249442 TI - Evidence for hemispheric specialization of lexical distinctions in bilingual Chinese-Mandarin speakers. AB - Lexical decision vocal reaction times of a group of English-proficient, Chinese Mandarin speakers and group of monolingual, English speakers were measured to unilaterally presented concrete and abstract English words. Results of an ANOVA showed a significant group x visual field x stimulus type interaction. Post-hoc analysis showed a significant right visual field advantage for the Chinese subjects. For the English speaking subjects, right visual field stimulations yielded significantly faster vocal reaction times to the abstract words than to the concrete ones, while the opposite occurred for left visual-field inputs. Also, a correlation between the two lateral conditions was significant for the Chinese subjects but not for the English speakers. These findings suggest that the English speakers evidenced dissociated left and right hemispheric linguistic processing while the Chinese subjects left hemisphere was responsible for the final phonological stages of linguistic analysis. Such findings support a phonological "monitor-user" hypothesis for cerebral dominance characteristics in bilingual Chinese speakers. PMID- 2249443 TI - Material specific learning during electrical stimulation of the human hippocampus. AB - Material specific learning was assessed during unilateral electrical stimulation of the hippocampus through intracerebrally implanted electrodes in 30 patients with unilateral temporal lobe epilepsy (TLE). Verbal learning significantly decreased in patients with right TLE after stimulation of the left, but not the right, hippocampus. No verbal learning impairment was observed in left TLE patients following stimulation of either hippocampus. Visuospatial memory performance significantly decreased following stimulation of the right hippocampus regardless of the side of seizure onset. Results suggest that the contralateral "nonepileptic" hippocampus does not assume the material specific mnestic functions of the dysfunctional hippocampus associated with longstanding epilepsy. PMID- 2249445 TI - Left handedness and handedness switch amongst the Chinese. AB - The incidence of left handedness amongst the Chinese, as in the case of people with more traditional cultures, is reported to be low. However, there is a group of native left handers, often unrecognized as such, who use the right hand for writing and drawing but the left hand for most other tasks. They had experienced pressure during childhood to shift their preferred hand from left to right. This paper compares the handedness profile, eyedness, footedness, and finger tapping performance of right handed, left handed, and handedness switch Chinese subjects. PMID- 2249444 TI - The contribution of an imagery code to verbal memory. AB - Free recall for auditorially presented spatial information was examined in a patient with a large right cerebral infarction. Despite normal verbal memory at immediate and 30-minute conditions, the patient exhibited a significant loss in verbal recall at 24 hours and a more severe deficit in the recall of the spatial components of prose passages across all delayed recall conditions. These results suggest that although the verbal code is important early in the learning process, spatial imagery exerts an increasing influence over time. Thus, reliance upon a left hemispheric mediated verbal encoding process may only allow for partial integration of linguistic and visuospatial properties. PMID- 2249446 TI - Apparent right neglect in patients with left visual neglect. AB - Two patients with unilateral left visual neglect were asked to bisect lines of different lengths. They showed, as expected, a rightward bias with longer lines. In contrast, they consistently transected very short lines (25 mm) to the left of the objective midpoint. The finding confirms a previous observation of similar behaviour but differs in other aspects that are of theoretical importance. PMID- 2249447 TI - Gerstmann syndrome: a case report. AB - A case of Gerstmann syndrome following a trauma is presented. After one month the patient showed the four symptoms of the Gerstmann syndrome associated with slight visual memory and constructional praxis deficits. Eight months later, however, he showed only dyscalculia, dysgraphia, right-left disorientation and finger agnosia, in accordance with selective damage of the left angular gyrus revealed by CT scan. The findings seems to support the existence and the localizing value of Gerstmann syndrome. PMID- 2249448 TI - Transient ischemic attacks presenting with a loss of pitch perception. AB - It has been suggested that the non-dominant hemisphere is specialized for receptive and expressive music and prosody. The present report describes a patient who experienced a series of non-dominant hemisphere transient ischemic attacks (TIA's) which included an inability to perceive intonation during one episode, and a failure to perceive melody during another. The perceptual losses during these TIA's are consistent with experimental results which suggest that the non-dominant hemisphere is specialized for complex-pitch processing. In some instances, amusia, dysprosody, and aprosodia reflect a common functional deficit. PMID- 2249449 TI - Failure to manipulate objects secondary to active touch disturbance. AB - A peculiar type of sensori-motor disturbance consequent to a lesion in the contralateral postcentral gyrus was reported. The symptom was characterized by motor clumsiness of the left hand without loss of strength and with preserved finger movements on visual imitation. Motor difficulty was most marked when the patient had to manipulate an object. The analysis of the patient's behavior and of his sensory deficits suggests that the basis of the clumsiness was a deficit in active touch perception. PMID- 2249450 TI - Rapid and uniform electromagnetic heating of aqueous cryoprotectant solutions from cryogenic temperatures. AB - Devitrification (ice formation during warming) is one of the primary obstacles to successful organ vitrification (solidification without ice formation). The only feasible approach to overcoming either devitrification or its damaging effects in a large organ appears at present to be the use of some form of electromagnetic heating (EH) to achieve the required high heating rates. One complication of EH in this application is the need for warming within a steel pressure vessel. We have previously reported that resonant radiofrequency (RF) helical coils provide very uniform heating at ambient temperatures and low heating rates and can be modified for coaxial power transmission, which is necessary if only one cable is to penetrate through the wall of the pressure vessel. We now report our initial studies using a modified helical coil, high RF input power, and cryogenic aqueous cryoprotectant solutions [60% (w/v) solution of 4.37 M dimethylsulfoxide and 4.37 M acetamide in water and 50% (w/w) 1,2-propanediol]. We also describe the electronic equipment required for this type of research. Temperatures were monitored during high-power conditions with Luxtron fiberoptic probes. Thermometry was complicated by the use of catheters needed for probe insertion and guidance. The highest heating rates we observed using catheters occurred at temperatures ranging from about -70 to -40 degrees C, the temperature zone where devitrification usually appears in unstable solutions during slow warming. We find that in this range we can achieve measured heating rates of approximately 300 degrees C/min in 30- to 130-ml samples using 200 to 700 W of RF power without overheating the sample at any point. However, energy conservation calculations imply that our measured peak heating rates may be considerably higher than the true heating rates occurring in the bulk of our solutions. We were able to estimate the overall true heating rates, obtaining an average value of about 20 degrees C/min/100 W/100 ml, which implies a heating efficiency close to 100%. It appears that it should be possible to warm vitrified rabbit kidneys rapidly enough under high-pressure conditions to protect them from devitrification. PMID- 2249451 TI - Fracture faces and other interfaces as ice nucleation sites. PMID- 2249452 TI - Vitrification of organized tissues. PMID- 2249453 TI - Physical problems with the vitrification of large biological systems. AB - Vitrification is an attractive potential pathway to the successful cryopreservation of mature mammalian organs, but modern cryobiological research on vitrification to date has been devoted mostly to experiments with solutions and with biological systems ranging in diameter from about 6 through about 100 microns. The present paper focuses on concerns which are particularly relevant to large biological systems, i.e., those systems ranging in size from approximately 10 ml to approximately 1.5 liters. New qualitative data are provided on the effect of sample size on the probability of nucleation and the ultimate size of the resulting ice crystals as well as on the probability of fracture at or below Tg. Nucleation, crystal growth, and fracture depend on cooling velocity and the magnitude of thermal gradients in the sample, which in turn depend on sample size, geometry, and cooling technique (environmental thermal history and thermal uniformity). Quantitative data on thermal gradients, cooling rates, and fracture temperatures are provided as a function of sample size. The main conclusions are as follows. First, cooling rate (from about 0.2 to about 2.5 degrees C/min) has a profound influence on the temperature-dependent processes of nucleation and crystal growth in 47-50% (w/w) solutions of propylene glycol. Second, fracturing depends strongly on cooling rate and thermal uniformity and can be postponed to about 25 degrees C below Tg for a 482-ml sample if cooling is slow and uniform. Third, the presence of a carrier solution reduces the concentration of cryoprotectant needed for vitrification (CV). However, the CV of samples larger than about 10 ml is significantly higher than the CV of smaller samples whether a carrier solution is present or not. PMID- 2249454 TI - Retention of endothelium-dependent vasodilatory responses in canine coronary arteries following cryopreservation. AB - In the present study, the cryoprotective effect of dimethyl sulfoxide (Me2SO) and fetal calf serum (FCS) on coronary endothelium and endothelium-dependent relaxation (EDR) responses was studied in isolated canine coronary arteries following cryostorage at -75 degrees C. Compared to the freshly isolated coronary arteries, the EDR responses to acetylcholine, thrombin, and calcium ionophore were not significantly altered following 1 day storage at -75 degrees C in the presence of 1.8 M Me2SO and 20% FCS. Prolonged cold storage to 7 days, however, resulted in a slight, but significant, rightward shift of the concentration response curves of acetylcholine and thrombin, but not calcium ionophore. The maximum relaxant response after 7-day cryostorage was 80 to 85% of fresh controls. Omission of FCS from the cryostorage incubation medium further accentuated the loss of EDR responses to all three endothelium-dependent vasodilators tested. Scanning electron microscopic examinations of the intimal surface of the Me2SO and FCS cryostored canine coronary arteries confirmed the preservation of intimal endothelial cells following 1 or 7 days of storage at -75 degrees C, while significant patches of loss of endothelial cells were observed in the arteries cryostored only in the presence of Me2SO. No significant inhibitory effect of cryostorage was observed for the direct, endothelium independent relaxation induced by isoproterenol, regardless of the presence or absence of FCS. These results demonstrate that slow freezing of canine coronary arteries to -75 degrees C in Krebs-Henseleit solution containing Me2SO and FCS provides good preservation of the vascular smooth muscle function and endothelium dependent vasodilatory responses. PMID- 2249455 TI - Mechanism of freeze-thaw damage to liver alcohol dehydrogenase and protection by cryoprotectants and amino acids. AB - Multiple freeze-thaw (FT) cycles, with complete melting between cycles, resulted in an exponential decline in liver alcohol dehydrogenase (LADH) enzyme activity. The reduction in activity of LADH as a result of FT damage was proportional to the decrease in the intensity of the tryptophan fluorescence of the enzyme. Treatment with urea resulted in a similar relationship between tryptophan fluorescence intensity and inactivation. Evidence from fluorescence and activity studies from the same sample, as well as gel electrophoresis, indicates that damage to LADH from a FT cycle, resulting in inactivation, is likely an unfolding of the enzyme rather than separation of subunits or aggregation of enzymes at the enzyme concentrations and cooling rates used. A nonexponential decline in enzyme activity, as a function of the number of FT cycles, can be achieved if complete melting between cycles is not allowed or if the samples are stored at +4 degrees C for 24 hr following the last FT cycle, prior to assay. In the latter case, a partial recovery in enzyme activity is seen. "Seeding," while lowering the enzyme activity, is desirable to achieve consistent results without the artifacts that are introduced if not used. Amino acids were tested for their effectiveness as cryoprotectants. From the results of this study, the mean fractional area loss of amino acid residues upon incorporation in globular proteins (f) is inversely proportional to the FT protection by these free amino acids. Thus, amino acid residues which tend to be found at the surface of proteins (e.g., glutamate) improve the FT survival of LADH, when added as the free amino acid, while those amino acids which are found in the interior of proteins (e.g., valine, leucine) sensitize LADH to FT damage. The pattern of protection ("fingerprint") of LADH by various amino acids is different from that of living cells. Furthermore, unlike the case with cells, glutamine and DMSO do not act independently when protecting LADH. PMID- 2249456 TI - Effects of low temperature on contraction in papillary muscles from rabbit, rat, and hedgehog. AB - During hibernation the body temperature may fall to only a few degrees above 0 degree C. The heart of the hedgehog continues to function whereas the hearts of nonhibernating mammals stop beating. The present study was performed to investigate and compare the mechanical responses to hypothermia in rabbits, rats, and hedgehogs. Isometric force was recorded from papillary muscles mounted in an organ bath and effects of hypothermia on the mechanical restitution curve were also compared. A reduction of bath temperature from 35 degrees C caused an increase in peak developed force. Maximum force was seen at 20 degrees C in the rabbit, 15 degrees C in the rat, and 10 degrees C in the hedgehog preparations. In all the species there was a similar prolongation of time to peak force and of time from peak to half-relaxation as temperature was lowered. An increase in resting force and after-contractions were recorded in the rabbit and rat muscles at temperatures below 15 and 10 degrees C, respectively. The rabbit and rat preparations became inexcitable at temperatures below 10 and 5 degrees C, respectively. The hedgehog papillary muscle, on the other hand, still contracted at 0 degree C and did not show increased resting force nor after-contractions. The results are consistent with the hypothesis that there is a calcium overload in cardiac cells from rabbit and rat at low temperatures but there is no calcium overload in the hedgehog muscle during hypothermia. PMID- 2249457 TI - Freezing of isolated thylakoid membranes in complex media. VI. The effect of pH. AB - Thylakoid membranes isolated from spinach leaves (Spinacia oleracea L. cv. Monatol) were used as a model biomembrane system for evaluating the significance of the hydrogen ion activity for cryoprotection. After freeze-thaw treatment in a buffered complex medium adjusted to various pH, light-induced photosynthetic membrane reactions were determined at optimum proton concentration. When thylakoids were suspended at hydrogen ion activities above and below the physiologically important pH range, irreversible inhibition of membrane functions was significantly less distinct after freezing at -15 degrees C than after storage for the same time at 0 degree C. It is suggested that thylakoid preservation at subfreezing temperatures could be due to temperature- and concentration-induced changes of the proton activity in the unfrozen part of the system and retardation of the temperature-dependent aging processes of the isolated membranes. In addition, the increase in the concentration of cryoprotective compounds during freezing could stabilize chloroplast membranes against the deleterious effect of unfavorable high and low proton concentrations. Thylakoid injury brought about by lowering the pH was primarily due to dissociation of the chloroplast coupling factor (CF1), which increased the proton permeability of the membranes and caused inhibition of photophosphorylation. In media adjusted to more alkaline pH, inactivation of the water oxidation system was an initial result of membrane damage. Then, noncyclic photophosphorylation was limited by photosystem II-mediated electron flow. Photosystem I-driven electron transport was substantially more stable over a wide pH range. PMID- 2249458 TI - Freeze-drying of Streptococcus thermophilus: a comparison between the vacuum and the atmospheric method. AB - Frozen suspensions of Streptococcus thermophilus were freeze-dried in a vacuum or a fluidized adsorbent bed at atmospheric pressure. Optimum operating conditions for each process were defined. For the duration of processing and survival rate of bacteria, in each case vacuum freeze-drying seemed more satisfactory than atmospheric pressure freeze-drying. The use of reconstituted skimmed milk as a suspension medium provides good protection for S. thermophilus. PMID- 2249459 TI - A new approach to the cryopreservation of hepatocytes in a sandwich culture configuration. AB - Current methods of cryopreservation of hepatocytes in single cell suspensions result in low overall yields of hepatocytes, demonstrating long-term preservation of hepatocellular functions. A novel culture method has recently been developed to culture liver cells in a sandwich configuration of collagen layers in order to stabilize the phenotypic expression of these cells in vitro (J. C. Y. Dunn, M. L. Yarmush, H. G. Koebe, and R. G. Tompkins, FASEB J. 3, 174, 1989). Using this culture system, rat hepatocytes were frozen with 15% (v/v) Me2SO to -70 degrees C, and stored at approximately -100 degrees C. Following rapid thawing, long-term function was assessed by measuring albumin secretion in culture for 7-14 days postfreezing. Comparison was made with cryopreservation of liver cells in single cell suspensions. Cryopreservation of liver cells in suspension resulted in only a 2% yield of cells which could be successfully cultured; albumin secretion rates in these cultured cells over 48 hr were 26-30% of secretion rates for nonfrozen hepatocytes. Freezing cultured liver cells in the sandwich configuration after 3, 7, and 11 days in culture maintained 0, 26, and 19% of the secretion rates of nonfrozen hepatocytes, respectively. Morphology of the cryopreserved cells appeared grossly similar to cells without freezing; however, this morphological result was patchy and represented approximately 30% of the cells in culture. These results represent the first demonstration of any quantitative long-term preservation of hepatocellular function by cryopreservation, suggesting that cultured hepatocytes can survive freezing and maintain function. PMID- 2249460 TI - SA Wenckebach. PMID- 2249461 TI - Mandatory HIV testing in critical care/emergency patients. AB - Testing for the presence of the human immunodeficiency virus (HIV) remains one of the most controversial issues of this decade. Among persons diagnosed to be HIV positive, social ostracism and exaggerated atypical behavior are common. The resulting impact on the delivery of healthcare services to the seropositive patient has raised many ethical and professional dilemmas. Discussion of HIV testing and the subsequent effects of seropositivity on the delivery of healthcare will be emphasized. PMID- 2249462 TI - DIC: the insidious killer. AB - Disseminated intravascular coagulation (DIC) is not a disease but an abnormal syndrome that is always secondary to another process. Because its symptomatology is varied and subtle, frequent assessments of body systems must be conducted. This article and its plan of care are designed to assist the nurse in the effective management of the DIC patient. PMID- 2249463 TI - Intraosseous infusion. AB - Intraosseous infusion has been documented for many decades to be a safe, fast, and effective method of fluid and medication administration. Complications are infrequent and the benefits generally far outweight the risks. Described in this article are: anatomic considerations, absorption, indications, complications, use in cardiopulmonary arrest, and insertion techniques. PMID- 2249464 TI - An unusual neurologic problem: Werdnig-Hoffmann disease. AB - Werdnig-Hoffmann Disease, its pathophysiology, and the resulting symptoms are described in this article. A case study is presented with treatment goals outlined, and the appropriate nursing interventions are delineated. PMID- 2249465 TI - Acute Guillain-Barre syndrome. PMID- 2249466 TI - Fluid resuscitation following multiple trauma. AB - The initial minutes and hours of nursing care of the trauma victim make a critical difference in the patient's chance for recovery. The critical care and ED nurse's ability to provide fluid resuscitation rapidly to augment the patient's flagging vascular volume is critical to the maintenance of circulation. By administering the most appropriate solution to meet the trauma patient's physiologic requirements, the nurse ensures that the patient will have an adequate circulating volume to meet the oxygenation and nutritional requirements of body tissues. Early, rapid fluid resuscitation is essential to stave off noncompensatory, irreversible shock. By implementing specific nursing care strategies to increase the flow of IV solutions to the patient, the nurse combats the nursing diagnosis appropriate for almost every multiple trauma victim: Fluid Volume Deficit. PMID- 2249467 TI - Salivary gland tumors. PMID- 2249468 TI - Chromosome analysis guidelines--preliminary report. Association of Cytogenetic Technologists Task Force. PMID- 2249469 TI - Isolation and characterization of cell hybrids containing human Xp-chromosome fragments. AB - We have subjected C12D, a Chinese hamster hybrid containing only the human X chromosome, to 6-thioguanine selection. The majority of the derivative clones retained rearranged Xp-fragments, which were characterized by using a combination of enzyme markers, DNA probes, and in situ hybridization. Two of these, TG2 and TG5sc9.1, contained only an Xpter----p21 fragment and should be an ideal resource for directed cloning from this region. A possible mechanism for the specific retention of Xp-fragments is discussed. PMID- 2249470 TI - Combined GTG-banding and nonradioactive in situ hybridization improves characterization of complex karyotypes. AB - Nonradioactive in situ hybridization (ISH) using biotinylated centromere probes for chromosomes 1, 6, 7, 10, 16, 17, 18, and the X, respectively, was combined with GTG-banding to study cytogenetic changes in two different ovarian cancer cell lines. ISH was performed after GTG-banding on the same metaphase. The use of a low trypsin concentration (0.01%) in the banding procedure was essential for subsequent ISH. This combined approach allows the detection of subtle chromosomal rearrangements and appears to aid the identification of marker chromosomes. PMID- 2249471 TI - XYY spermatogenesis in XO/XY/XYY mosaic mice. AB - The relative frequencies of XYY and XY cells in XO/XY/XYY mosaic mice were compared between somatic cells (bone marrow) and spermatogonia, and between spermatogonia and pachytene or MI spermatocytes. The results indicated there was no selection either for or against XYY spermatogonia. There was, however, a strong selection against XYY spermatocytes during pachytene, with their almost total elimination by the first meiotic metaphase. At pachytene, most XYY cells had trivalent or X univalent/YY bivalent configurations. These findings are contrasted with previous studies of XYY spermatogenesis in mice and are discussed with respect to a model that invokes sex-chromosome univalence as the cause of XYY spermatogenic failure. PMID- 2249472 TI - Synaptonemal complex analysis in Talpa occidentalis spermatocytes (Insectivora, Mammalia). II. Evolution of the X-chromosome self-pairing process. AB - Zygotene and pachytene configurations of the X chromosome were studied in whole mount, silver-stained preparations of spermatocytes from XY males from a population of Talpa occidentalis in which sex reversal has been described. The most striking finding in this study was a self-pairing conformation of the axial (differential) element of the X chromosome. This self-pairing was markedly constant in the site of initiation, which invariably involved the distal free end of the X and the region beyond the X-Y pairing segment, so that X-Y synapsis was never disturbed. In addition, self-pairing occurred later than autosomal synapsis and was accompanied by thickening of the axes, although this seemed to occur after the formation of an ordinary synaptonemal complex. The etiology of this phenomenon may be based on residual homology, possibly due to conservation of a primitive isochromosome throughout the karyotypic evolution of this species. However, the possible relationship between self-pairing and sex reversal remains obscure. PMID- 2249473 TI - Deletion of the pseudoautosomal region and lack of sex-chromosome pairing at pachytene in two infertile men carrying an X;Y translocation. AB - Two males with a 46,Y,der(X),t(X;Y)(p22.3;q11) complement were referred independently for evaluation of sterility with azoospermia. Both patients exhibited minimal symptomatology, characterized only by psychological disturbances. Study of X-chromosome breakpoints with pseudoautosomal probes 68B (DXYZ2 elements), 113D (locus DXYS15), and 19B (locus MIC2) indicated in both patients that at least 97% of the X pseudoautosomal sequences are lost. Hybridization with Xp22.3-specific probes DXS283, DXS284, and DXS31 shows that these loci are retained on the rearranged chromosome. Thus, the X-chromosome breakpoints are located close to the proximal boundary of the pseudoautosomal region, between MIC2 and DXS284. PMID- 2249474 TI - Nondisjunction, disturbances in spindle structure, and characteristics of chromosome alignment in maturing oocytes of mice heterozygous for Robertsonian translocations. AB - To correlate the chromosomal constitution of meiotic cells with possible disturbances in spindle function and the etiology of nondisjunction, we examined the spindle apparatus and chromosome behavior in maturing oocytes and analyzed the chromosomal constitution of metaphase II-arrested oocytes of CD/Cremona mice, which are heterozygous for a large number of Robertsonian translocation chromosomes (18 heterobrachial metacentrics in addition to two acrocentric chromosomes 19 and two X chromosomes). Spreading of oocytes during prometaphase 1 revealed that nearly all oocytes of the heterozygotes contained one large ring multivalent, apart from the bivalents of the two acrocentric chromosomes 19 and the X chromosomes, indicating that proper pairing and crossing-over between the homologous chromosome arms of all heterobrachial chromosomes took place during prophase. A large proportion of in vitro-matured oocytes arrested in metaphase II exhibited numerical chromosome aberrations (26.5% hyperploids, 40.8% hypoploids, and 6.1% diploids). In addition, some of the oocytes with euploid chromosome numbers (26.5% of the total examined) appeared to be nullisomic for one chromosome and disomic for another chromosome, so that aneuploidy levels may even be higher than expected on the basis of chromosome counts alone. Although oocytes of the complex heterozygous mice seemed able initially to form a bipolar spindle during first prometaphase, metaphase I spindles were frequently asymmetrical. Chromosomes in the multivalent did not align properly at the equator, centromeres of neighboring chromosomes in the multivalent remained maloriented, and pronounced lagging of chromosomes was observed at telophase I in oocytes obtained from the Robertsonian translocation heterozygotes. Therefore, disturbance in spindle structure and chromosome behavior appear to correlate with the chromosomal constitution in these oocytes and, ultimately, with failures in proper chromosome separation. In particular, reorientation appears to be a rare event, and malorientation of chromosomes may remain uncorrected throughout prometaphase, as we could not find many typical metaphase I stages in heterozygotes. This, in turn, could be the basis for malsegregation at anaphase and may ultimately induce a high rate of nondisjunction and aneuploidy in the oocytes of CD/Cremona mice, leading to total sterility in heterozygous females. PMID- 2249475 TI - Freemartinism in red deer (Cervus elaphus L.). AB - Several mixed-sex twins were produced by red deer treated with progesterone and pregnant mare's serum gonadotrophin. Of seven females karyotyped, two were 68,XX/68,XY chimeras. One male had the same chimeric karyotype as its female co twin. These are the first reported cases of freemartinism in deer. PMID- 2249476 TI - In situ hybridization to human chromosome 1 of a cDNA probe for the gene encoding the basement membrane heparan sulfate proteoglycan (HSPG). AB - A mouse partial cDNA clone of the heparan sulfate proteoglycan gene, an important component of basement membranes, has been mapped to human chromosome 1, band p 36.1, by in situ hybridization. No secondary sites of hybridization were observed. PMID- 2249477 TI - Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12----p13). AB - Human sex hormone-binding globulin (SHBG) is a plasma steroid transport protein which is known to be encoded by an autosomal gene. We have hybridized two separate cDNA probes, corresponding to the 5' and 3' portions of the coding sequence for SHBG, to human metaphase chromosomes in situ. In this way, the SHBG gene has been localized to the p12----p13 bands of chromosome 17. PMID- 2249478 TI - Localisation of neurone-specific enolase (ENO2) to 12p13. AB - We have localised the human cDNA for neurone-specific enolase (ENO2) to chromosome region 12p13 by in situ hybridisation. Two additional smaller peaks of hybridisation to specific chromosomal subregions were observed. That on chromosome 1p36 probably represents cross-hybridisation to the locus for nonneuronal enolase (ENO1), which has been previously localised to this chromosome and with which ENO2 shares homology. A further gene for a member of the enolase family may be responsible for the hybridisation to chromosome 17. PMID- 2249480 TI - Localization of the human luteinizing hormone/choriogonadotropin receptor gene (LHCGR) to chromosome 2p21. AB - Probes corresponding to human and porcine LH (luteinizing hormone) receptor cDNA were used for in situ hybridization to human chromosomes. This allowed us to assign the LH receptor gene to chromosome 2p21. PMID- 2249479 TI - Localization of human cardiac beta-myosin heavy chain gene (MYH7) to chromosome 14q12 by in situ hybridization. AB - The genes coding for each human cardiac myosin heavy chain (alpha-MHC and beta MHC, MYH6 and MYH7, respectively) are tightly linked and the alpha-MHC gene has been assigned to chromosome 14. In order to provide a more precise regional localization, in situ hybridization experiments were carried out using a 3H labeled probe derived from a beta-MHC genomic clone. The results demonstrated that the human cardiac MHC genes are located within the q12 band of chromosome 14. PMID- 2249481 TI - Localization of the insulin receptor-related receptor gene to human chromosome 1. AB - DNA encoding the insulin receptor-related receptor (IRR), a novel receptor whose predicted primary structure is similar to those of the insulin and insulin-like growth factor I receptors, has been used in Southern blot analysis of DNA from human x mouse somatic cell hybrids to assign the IRR gene (INSRR) to human chromosome 1. PMID- 2249483 TI - Mapping of the human type II collagen gene (COL2A1) proximal to fra(12) (q13.1) by nonisotopic in situ hybridization. AB - The human type II collagen gene (COL2A1) was mapped to chromosome 12 immediately proximal to fra(12)(q13.1) by the technique of nonisotopic (biotinylated) in situ hybridization. Thus, the COL2A1 gene was confirmed to be at the subband 12q13.11- --q13.12, in agreement with previous reports. These results are not in agreement with the localization (12q14.3) cited in Ropers and Craig (1989). PMID- 2249482 TI - Localization of human thyrotropin receptor gene to chromosome region 14q3 by in situ hybridization. PMID- 2249484 TI - Localization on pig chromosome 6 of markers GPI, APOE, and ENO1, carried by human chromosomes 1 and 19, using in situ hybridization. AB - In the pig, the linkage group around the halothane gene (HAL), composed of S-GPI HAL-H-A1BG-PGD, has been assigned to bands p1.2----q2.2 of chromosome 6. In man, ENO1-PGD and APOE-GPI constitute two syntenic groups situated on different chromosomes (1 and 19, respectively). Since GPI and PGD are linked in the pig, we have hybridized the human cDNA probes for ENO1 and APOE to pig chromosomes. These markers were assigned to pig chromosome 6, in the q2.2----q2.4 and cen----q2.1 regions, respectively, using in situ hybridization. Since GPI and APOE are situated in the same region, we combined the use of high resolution chromosome analysis and in situ hybridization to give a more precise localization in the q1.2 and q1.2----q2.1.2 regions of chromosome 6. A possible linear order of these genes is proposed. PMID- 2249485 TI - Assignment of the porcine growth hormone gene to chromosome 12. PMID- 2249486 TI - "The invisible light". PMID- 2249487 TI - Image quality and radiation levels in videofluoroscopy for swallowing studies: a review. AB - Inexpensive video recording equipment coupled to conventional x-ray fluoroscopes is now in widespread use by clinicians for the evaluation of patients with swallowing disorders. The prevalence and simplicity of this apparatus have encouraged its use by clinical specialists who are often not specifically trained in the safe use of x-ray equipment, and this may not be in the best interest of either the patient or the examiner. This has prompted an overview of the operating principles of videofluorescopy equipment. The factors governing image quality are discussed as well as potential hazards and protective measures for both patients and operator. A method of estimating the radiation dose to sensitive tissues from a typical swallowing study is included. PMID- 2249488 TI - Approaches to the patient with aspiration and swallowing disabilities. AB - Aspiration, or soiling of the tracheobronchial tree, can produce life-threatening pulmonary disease. Intermittent or persistent aspiration may cause symptoms including cough, intermittent fever, recurrent tracheobronchitis, atelectasis, pneumonia, and/or empyema. The pulmonary disease may be associated with weight loss, cachexia, and dehydration. In many cases the aspiration is caused by laryngeal dysfunction, allowing pulmonary contamination by swallowed material. In other cases the aspiration is caused by a dysfunction of the oral, pharyngeal, or esophageal phases of swallowing. In some cases the aspiration is caused by a combination of laryngeal and swallowing dysfunction. Geriatric patients are more likely to experience aspiration, since muscle weakness causing mechanical disability and neurologic impairment are more common in this age group. Therefore, with the ever-increasing aging of our population, these disabilities will be on the rise, with an associated increase in pulmonary disease and death. The approach to evaluation and management of these disorders must be based on an understanding of the underlying functional impairment. PMID- 2249489 TI - Esophageal motility in an adult with a congenital H-type tracheoesophageal fistula. AB - Congenital H-type tracheoesophageal fistulas (TEF) are rare. Long-standing respiratory symptoms are the most common presenting complaints. Patients with these fistulas have a congenital esophageal motor abnormality characterized by uncoordinated, low-amplitude peristalsis of the esophageal body; both low and normal lower esophageal sphincter pressures have been described. These findings persist despite fistula repair. A case history of an adult patient with congenital TEF is presented and the literature is reviewed. This patient is unusual in that esophageal symptoms (dysphagia) were more prominent than the usual respiratory symptoms. PMID- 2249490 TI - Acoustic technique for determining timing of velopharyngeal closure in swallowing. AB - A pure tone sound source was introduced at a nostril and monitored by a miniature accelerometer on the throat. During velopharyngeal closure in a swallow, the pure tone component in the accelerometer signal was attenuated. Throat accelerometer recordings were made simultaneously with videofluoroscopy of a modified barium swallow in adults with normal velopharyngeal mechanisms. It was verified that the period of sound attenuation corresponded to the period of velar closure. This noninvasive method of monitoring otherwise silent velopharyngeal closure holds promise for normative studies on swallowing function, as an adjunct method in longitudinal assessment, and as a training aid. PMID- 2249491 TI - Effects of a multidisciplinary management program on neurologically impaired patients with dysphagia. AB - Dysphagia is a major problem in patients with neurologic disorders. Aspiration pneumonia and impaired nutritional status are consequences of dysphagia that result in high morbidity and mortality rates. Assessment and treatment of the dysphagic patient by a multidisciplinary team have been advocated but to date the effects of such an approach have not been demonstrated quantitatively. This prospective study was conducted to determine if a dysphagia program would improve patients' caloric intake and body weight, decrease the instances of aspiration pneumonia, or improve patients' feeding ability. Patients were referred from a 26 bed neurology/neurosurgery unit. A time series design was utilized. The control group consisted of 15 patients (mean age = 46.1 years), managed according to the existing ward routine. Subsequently, nursing staff attended a dysphagia training program. Following this, the treated group of 16 patients, (mean age = 49.3 years) was assessed by the dysphagia team, using bedside and videofluoroscopic examinations to determine the specific swallowing disorder. An individualized treatment program was designed for each patient. The groups were compared on the basis of deviation from their baseline weight, deviation from ideal energy intake, and the incidence of aspiration pneumonia. Statistical analysis revealed that the groups were comparable in age, number of days on the study, and Glasgow Coma Scale score; and that a significant weight gain and increase in caloric intake occurred in the treated group. No incidence of aspiration pneumonia was reported in either group. We speculate that this may have been influenced by the meticulousness of the care delivered in an acute unit as well as greater attention to prevention given in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249492 TI - Motility changes in primary achalasia following pneumatic dilatation. AB - The changes in esophageal motility after pneumatic dilatation were evaluated prospectively in 51 patients with achalasia. The patients were evaluated for a median of 14 months. Pneumatic dilatation led to a clinical improvement in 41 patients. On manometric evaluation, a significant decrease in lower esophageal sphincter pressure was observed (28.4 +/- 14.9 mmHg vs. 13.5 +/- 7.2 mmHg; p = 0.001); the resting pressure of the esophageal body dropped from 4.8 +/- 4.2 mmHg above gastric baseline to 0.1 +/- 3.9 mmHg below gastric baseline. After therapy, peristaltic activity was present in 10/51 (20%) patients; in 1 case, complete relaxation of the lower esophageal sphincter was recorded. Treatment-induced motility changes could not be predicted by clinical history or the lower esophageal sphincter pressure before or after therapy. However, the resting pressure of the esophageal body before and after therapy was significantly lower in these patients in whom peristalsis recurred after therapy than in patients with an unchanged motility pattern. The reappearance of peristaltic activity after pneumatic dilatation was unrelated to lower esophageal sphincter pressure. In conclusion, motility disturbances of the esophageal body in patients with achalasia do not simply reflect the functional obstruction of the lower esophageal sphincter. These findings support the hypothesis that achalasia is not a distinct motility disturbance but should be regarded as part of a broad spectrum of different interrelated esophageal motility disorders. PMID- 2249493 TI - Social problem-solving skills of young physically abused children. AB - The ability of physically abused children to resolve hypothetical social problems was compared to the social problem-solving skills of a comparison group of nonabused children. Analyses indicated that the abused children generated a more narrow range of solutions and were more likely to perserverate on negative solutions. Implications for intervention and future research are made. PMID- 2249494 TI - Play in assessment and intervention in the childhood psychoses. AB - Diagnostic and therapeutic uses of play in the childhood psychoses are described. A play procedure suitable for consultative use with children is outlined, and research relating to identification of subgroups of childhood psychoses is reviewed. Case vignettes are employed to illustrate differential therapeutic uses of play with subgroups. PMID- 2249495 TI - Effects of an intensive self-esteem building therapeutic model on adolescents in psychiatric treatment. AB - An intensive two-week day hospital program for adolescent psychiatric clients was developed to build self-esteem. Results indicated that the clients' family relations improved, as did their leadership and affiliation skills. PMID- 2249496 TI - Coping and stress in families of child psychiatric inpatients: parents of children with depressive and schizophrenia spectrum disorders. AB - Coping and disruption were examined in parents of children with depressive and schizophrenia spectrum disorders. Parents described disruption in their family lives, relationships, leisure time, and work functioning. High maternal disruption was associated with the absence of intimate relationships and child chronicity. Parents most frequently reported using active cognitive coping strategies, but with the advantage of hindsight, advised seeking community resources for helping their children. PMID- 2249497 TI - Anorexia nervosa in adolescent males: a review and case study. AB - The clinical presentation of anorexia nervosa among males is quite rare. This paper examines the personality and developmental issues of anorexia nervosa in adolescent males through a comprehensive review of the literature and a case presentation. In addition, this paper will demonstrate the application of the empirical literature in the development of a conceptual model to identify critical diagnostic and psychotherapeutic issues within the assessment of a clinically rare case, a male adolescent with anorexia nervosa. PMID- 2249498 TI - Family characteristics of preschool social competence among black children in a Head Start Program. AB - Social competence has been suggested to serve a protective function in emotional functioning and may compensate for some deleterious experiences. This study found that adherence to family routines and older fathers were significant predictors of preschool social competence. The subjects were 91 black children enrolled in a metropolitan Head Start program who were rated for social competence by their teachers. PMID- 2249499 TI - The first joint meeting of the North-American Musculoskeletal Tumor Society and the European Musculoskeletal Oncology Society. Bologna, September 11-14, 1989. Proceedings. PMID- 2249501 TI - Resection of the sacrum for tumors. PMID- 2249500 TI - Giant cell tumor of the spine and sacrum. PMID- 2249502 TI - Clonal analysis of human chondrosarcoma. PMID- 2249503 TI - Operative procedures in tumors of the sacrum. Results of 26 cases. PMID- 2249505 TI - Total sacrectomy and lower spine resection for giant cell tumor: one case report. PMID- 2249504 TI - Sacral resections: experience of the I.O.R. bone tumor center. PMID- 2249506 TI - Histopathological grading of adult soft tissue sarcomas. PMID- 2249507 TI - The surgical margin in soft tissue sarcoma. PMID- 2249508 TI - Local recurrence and survival in soft tissue sarcomas: the relation of biopsy. PMID- 2249509 TI - The real impact of specialistic procedures and adequate surgery for soft tissue sarcoma. PMID- 2249510 TI - Anatomic extent of soft tissue sarcomas of the extremities: implications for surgical strategy. PMID- 2249511 TI - Limb-sparing surgery without radiotherapy for soft tissue sarcoma. PMID- 2249512 TI - Diagnosis of spinal sarcomas with emphasis on the immunohistochemical staining techniques. PMID- 2249513 TI - The use of intraoperative radiation therapy in the management of patients with non-metastatic high-grade soft tissue sarcomas: a preliminary report. PMID- 2249514 TI - New techniques in the management of soft tissue tumors: combined surgery and radiation therapy. PMID- 2249515 TI - End results in 130 cases of soft tissue sarcomas of the limbs and trunk walls, treated by a systematic radio-surgical association. Multivariate analysis of prognostic factors. PMID- 2249516 TI - Cellular yields and DNA content parameters in osteogenic sarcomas. PMID- 2249517 TI - Soft tissue sarcomas: the experience at the Istituto Ortopedico Rizzoli. PMID- 2249518 TI - The management of unresectable large desmoid tumors: a review of three cases. PMID- 2249519 TI - Angiomatoid variant of epithelioid sarcoma. The value of immunohistochemistry in the differential diagnosis. PMID- 2249520 TI - Rhabdomyosarcoma of the appendicular skeleton: survival and treatment considerations. PMID- 2249521 TI - Schwannoma. A true soft tissue tumor, or autonomous disease? Report of 123 malignant lesions. PMID- 2249522 TI - Composite fixation of segmental bone/joint defect replacement (SDR) prostheses. Biological and biomechanical justifications. PMID- 2249523 TI - Composite fixation of segmental bone/joint defect replacement (SDR) prostheses. Clinical results and functional/device assessment. PMID- 2249524 TI - Cementless modular prostheses. Basic concepts and evolution. PMID- 2249525 TI - Cementless modular prosthesis. Results and complications. PMID- 2249526 TI - DNA ploidy as a prognostic indicator in human osteosarcoma. PMID- 2249527 TI - Cytogenetic analysis of giant cell tumors of bone; diagnostic and prognostic implications. PMID- 2249528 TI - Subchondral replacement: a comparative analysis of reconstruction with methyl methacrylate or autogenous bone graft. PMID- 2249529 TI - M.R.I. study of bone graft incorporation. PMID- 2249530 TI - Adjuvant management of benign tumors; basic concepts of phenol and cement use. PMID- 2249531 TI - Liquid nitrogen as an adjunct. PMID- 2249532 TI - Curettage of giant cell tumor of bone. Introduction--material and methods. PMID- 2249533 TI - Curettage of giant cell tumor of bone. Factors influencing local recurrences and metastasis. PMID- 2249534 TI - Curettage of giant cell tumor of bone. The effect of surgical technique and adjuvants on local recurrence rate. PMID- 2249536 TI - Curettage of giant cell tumor of bone. Complications. PMID- 2249535 TI - Curettage of giant cell tumor of bone. Treatment of local recurrences. PMID- 2249538 TI - A system for the classification of skeletal resections. PMID- 2249539 TI - Effect of preoperative chemotherapy on nuclear DNA content in osteosarcoma. PMID- 2249537 TI - Curettage of giant cell tumor of bone. Reconstruction with subchondral grafts and cement. PMID- 2249540 TI - Giant-cell tumor in the radius: aggressiveness and soft tissue recurrence. PMID- 2249541 TI - Giant-cell tumor of the radius. PMID- 2249542 TI - Chronic tibial lesions. PMID- 2249543 TI - Hip reconstruction following internal hemipelvectomy for primary periacetabular sarcomas. PMID- 2249544 TI - Experience and conclusions from a series of 50 rotation plasties. PMID- 2249545 TI - Pelvic allografts in surgery of pelvic bone tumors. PMID- 2249546 TI - Preservation of the extremity in bone and soft tissue sarcomas with multidisciplinary treatment. PMID- 2249547 TI - Ewing's sarcoma. Fifteen years of experience. PMID- 2249548 TI - The role of surgery in the local treatment of Ewing's sarcoma of the extremities. PMID- 2249549 TI - A new approach to the resection of pulmonary osteosarcoma metastases: results of aggressive metastasectomy. PMID- 2249550 TI - Tumor necrosis following radiation therapy and/or chemotherapy for canine osteosarcoma. PMID- 2249551 TI - Spontaneous necrosis in osteosarcomas. PMID- 2249552 TI - Parametric imaging of 99mTc methylene diphosphonate biokinetics in osteosarcoma for preoperative evaluation of chemotherapy-induced necrosis. PMID- 2249553 TI - MRI and bone scan in osteosarcoma. Is preoperative assessment of tumor necrosis possible? PMID- 2249554 TI - The potential of MRI in preoperative evaluation of chemotherapy-induced necrosis in osteosarcoma and Ewing's sarcoma. PMID- 2249555 TI - Morphological investigation of tumor growth and distribution of viable tumour areas in osteosarcomas after chemotherapy. PMID- 2249556 TI - Long-term followup in the cure of osteogenic sarcoma. The Southwest Oncology Group. PMID- 2249557 TI - TMMR-2, a monoclonal antibody to human osteosarcoma. PMID- 2249558 TI - Intensified chemotherapy with ifosfamide (IFO) and influence of intraarterial (i.a.) versus intravenous (i.v.) infusion of cisplatinum (DDP). Preliminary results. PMID- 2249559 TI - Neoadjuvant chemotherapy for osteosarcoma of the extremities: the Rizzoli Institute experience. PMID- 2249560 TI - Molecular genetic changes in musculoskeletal sarcomas. PMID- 2249561 TI - Prognosis of osteosarcoma with "skip" metastasis. PMID- 2249562 TI - The effect of doxorubicin on local recurrence following marginal resection in the MGH-OGS murine osteosarcoma. PMID- 2249563 TI - Surgical margins in osteosarcoma. PMID- 2249564 TI - Limb salvage for high grade osteosarcoma. Considerations about margins. PMID- 2249565 TI - The surgical margins in 41 high grade bone sarcomas treated with the Morton Eilber protocol. PMID- 2249566 TI - Margins, necrosis and local recurrence after conservative surgery in osteosarcoma. PMID- 2249567 TI - Strategy for the surgical treatment of primary bone tumors of the spine in children. PMID- 2249568 TI - Quantitative aspects of tumor growth. PMID- 2249569 TI - Total vertebrectomy for malignant tumors by combined approach. PMID- 2249570 TI - Total vertebrectomy as treatment of malignant tumors of the spine. PMID- 2249571 TI - Total spondylectomies above the sacrum. PMID- 2249572 TI - Staging, biopsy, surgical planning of primary spinal tumors. PMID- 2249573 TI - [The significance of retinal nerve fiber layer examination in the diagnosis of glaucoma]. AB - To evaluate the significance of nerve fiber layer (NFL) changes in the diagnosis of glaucoma, the authors examined 197 cases (347 eyes) of normal subjects, primary open angle glaucoma (POAG), low tension glaucoma (LTG) and suspects of these two types of glaucoma. The sensitivity of NFL atrophy to glaucoma was high: in POAG eyes with field loss, 88.9% (64/72) had NFL atrophy. In 123 normal eyes, NFL atrophy was found in only one eye, the specificity of NFL atrophy being 99.2%. All LTG patients and suspects of LTG had NFL atrophy. In the fellow eyes of POAG with normal fields and eyes of POAG suspects, NFL defects occurred in 53.8% (7/13) and 20.6% (15/73) respectively. The examination of NFL is a simple procedure; the nerve fibers themselves are directly observed rather than their function. When half of the thickness of NFL is lost, it Will be manifested clinically. With its high sensitivity and specificity, NFL atrophy can be regarded as an important indicator in the diagnosis of glaucoma. PMID- 2249574 TI - [The relation of fluorescein angiography in low tension glaucoma with retinal nerve fiber layer defect and visual field damage]. AB - The fluorescein angiography, visual field and retinal nerve fiber layer defects (RNFLD) in 23 patients (35 eyes) with low tension glaucoma (LTG) showed that there was a marked positional correspondency between the fluorescein filling defect of the optic disc and the RNFLD (91.4%) or the visual field defect (77.1%). Besides, the rate of positional correspondent between the RNFLD and visual field defect was 80.0%. The study indicated that RNFLD and visual field defect of LTG are related to ischemia of the optic disc. PMID- 2249575 TI - [Correlation between the retinal nerve fiber layer defects (RNFLD) and visual field defects in primary open-angle glaucoma]. AB - The RNFLD and the visual field in 73 cases (124 eyes) of primary open-angle glaucoma were studied. It was found that the early RNFLDs were usually local, as combed-hair, slit-like, or wedge shaped defects, while in the medium or late stage, diffuse RNFL atrophy or mixed RNF-LD was the rule. In the group of localized RNFLDs, 8.8% of the patients showed no visual field anomalies, indicating that RNFL damages preceded visual field damages; in the rest of the patients, visual field defects corresponded with the RNFLD in 86.7% of the cases. In patients of the medium or late stage with mixed or diffuse RNFLD, nasal steps and isopter constriction were usually found that corresponded perfectly with the RNFLD. PMID- 2249576 TI - [Observations on the corneal endothelium in glaucoma]. AB - The corneal endothelia in 87 cases of unilateral glaucoma were studied with the TOCEB-160 IV specular photomicroscope, and the healthy fellow eyes served as controls. The endothelial cell density was found decreased in majority of the morbid eyes by an average 12.7% in acute angle-closure glaucoma (34 cases), by 5.34% in chronic angle-closure glaucoma (23 cases), and by 12.4% in glaucoma cyclitis syndrome (30 cases). The average diminution of endothelial cell densities after filtering operations in 16 eyes was 10.2%, and after Nd:YAG laser iridotomy it was 5.11%. The authors are of the opinion that estimation of endothelial cells before operations and precautions against endothelial damage during operations invading the anterior chamber are necessary, especially for cases with risk factors such as trauma, uveitis, persistent high IOP, old age, or history of intra-ocular surgery. PMID- 2249577 TI - [Clinical features and prognosis of retinal lattice degeneration]. AB - 110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand. PMID- 2249578 TI - [Oblique muscle dysfunction and cyclotropia]. AB - The disc-fovea angle was calculated from the fundus photo by measuring the distance of fovea to the geometric center of the disc and the distance of fovea to the horizontal meridian through the disc center. The authors found the average disc-fovea angle of 40 normal individuals to be extorsion 7.43 degrees; and the diagnosis of cyclotropia was made for patients with extorsion over 14.20 degrees or intorsion, and those in whom the disc-fovea angle difference between both eyes was 8 degrees or over. In 9 cases of AV syndrome, 86% (12/14) of the V pattern cases associated with inferior oblique overaction were excyclotropic, and 75% (3/4) of the A pattern cases were incyclotropic. In 5 cases of superior oblique paresis, 86% (6/7) of the diseased eyes were excyclotropic, whether the function of the antagonistic was normal. The authors concluded that fundus photos could serve as a basis for diagnosis of cyclotropia. PMID- 2249579 TI - [Complications associated with soft hydrophilic contact lenses]. AB - The authors report 89 cases of ocular complications associated with soft hydrophilic contact lenses, including corneal abrasions, corneal ulcers, punctate corneal epithelial erosions, aphakic corneal edema, and superior limbal keratoconjunctivitis. Soft contact lenses interfere with the integrity and function of the tear film, so that corneal metabolism is affected, predisposing the cornea to infections by Pseudomonas, Acanthamoebia, fungus and virus. The incidence of the complications is high; therefore, due attention should be devoted to their prevention and treatment. PMID- 2249580 TI - [4 mm incision for cataract extraction: a report of 728 eyes]. AB - The author analyzed 728 cataract extractions performed through 4 mm incisions during January 1972 to January 1987. 230 of the operations were done by phaco emulsification, 320 by lensectomy, and 178 by aspiration. 580 of the eyes were followed up 1-15 years, when 87.8% of the eyes had corrected vision of 0.06 or over, and 48.8% of 0.6 or over. The technical aspect of cataract extraction through a small incision was evaluated and corneal astigmatism thereof discussed. PMID- 2249581 TI - [Ultrasonic diagnosis of intraocular cysticercus]. AB - Intraocular cysticerci are mostly located in the subretinal space or vitreous. When the fundus is obscured by exudate or hemorrhage, the diagnosis becomes very difficult with the ophthalmoscope or biomicroscope. The authors performed A- and B-scan echographic studies on 20 cases of intraocular cysticercus during February 1985 to December 1988; it was found that B-scan was very useful in diagnosing intraocular cysticercus with regard to its location and relation to surrounding tissues. Several cases with typical echograms are presented with discussions. The ultrasonic diagnoses were confirmed by surgery. PMID- 2249582 TI - [An ultrastructural study of the optic papilla in experimental hypotony]. AB - The ultrastructures of the optic papilla at different intervals during experimental hypotony in rabbits were studied by transmission electron microscopy, with the results that after 14 days the axons of optic nerve fibers showed signs of degeneration; after 21 days there appeared marked pathological changes, and after 30 days there were serious irreversible pathological changes. These findings suggest that clinical hypotony, such as occurs after glaucoma operations particularly, should be duly attended to. PMID- 2249583 TI - [A simplified tissue culture technique for rabbit corneal cells]. AB - A simplified technique for short-term culture of pure populations of rabbit corneal epithelial or endothelial cells has been developed. Rabbit corneas were placed on the concave agarose surfaces of a 24 well culture plate, treated briefly with a solution of trypsin and ethylenediamine tetracetic acid, and transferred, epithelial surface or endothelial surface down as needed, to another 24 well culture plate. Within 24 hours, the epithelial cells or endothelial cells grew over the surfaces of the wells. This technique is simple and economical for the initiation of primary culture of rabbit corneal epithelial or endothelial cells for use in various experiments. PMID- 2249584 TI - [Measurement and analysis of the horizontal corneal diameter in the newborn]. PMID- 2249585 TI - [Retinoblastoma gene in human esophageal cancer]. AB - Retinoblastoma gene (Rb) is a tumor suppressor gene. In 21 esophageal cancer and 43 pericancerous non-tumor samples obtained from patients who had undergone surgery for esophageal cancer in Linxian County, a high incidence area of esophageal cancer, Rb gene was studied. DNAs were extracted from the above esophageal tissues, then were separately digested with Hind III, EcoRI, BamHI, PstI, MspI, HpaII and subjected to Southern analysis. The Southern blots were sequentially probed with two fragments of Rb cDAN clone: 0.9 kb and 3.8 kb. Of 43 adjacent non-tumor tissues examined, 15 were found to have structural anomaly (34.9%). Seven of 21 esophageal cancers also showed structural anomaly (33.3%). In order to study the cause of Rb gene deletion, esophageal carcinoma of human fetal origin induced by N-methyl-N-benzylnitrosamine (NMBzA) in nude mice were similarly examined and found to be deleted of Rb gene. Thus, deletional inactivation of Rb gene may play an important role in the pathogenesis of esophageal cancer in this high-risk area. N-nitrosamine may play a causative role in deletion of Rb gene. The above data for the first time demonstrate structural anomaly of Rb gene in esophageal cancer and confirm that chemical carcinogens, such as N-nitrosamines, can delete the antioncogene. PMID- 2249586 TI - [Genotoxicity of fried fish extract, MeIQ and inhibition by green tea antioxidant]. AB - Fried fish extract (FFE) and its related compound MeIQ showed potent genotoxicity to mammalian cells. FFE and MeIQ induced an increase in SCE or micronuclei in V79 cells in the presence of S9mix and an increase in SCE in IAR20 cells without S9mix UDS of rat primary hepatocytes was also significantly increased after treatment by FFE or MeIQ. Green tea antioxidant strongly inhibited the increase in SCE and micronuclei induced by FFE or MeIQ in V79 or IAR20 cells. The inhibitory effect of antioxidant on UDS was also observed in rat primary hepatocytes treated with FFE or MeIQ. The results indicate that mutagens and/or carcinogens might be produced during cooking of meat under high temperature. Frequent intake of green tea might be beneficial to human health. PMID- 2249587 TI - [Genetic etiology of esophageal cancer. V. Fragile sites on chromosome of cultured lymphocytes from members of high risk cancer families in Linxian County]. AB - The chromosome fragile sites of cultured peripheral lymphocytes from 40 members of 4 high risk cancer families and 10 members of 4 low risk cancer families in Linxian County were analysed. The results showed that 46 fragile sites in 7045 lymphocytes expression at 502 times (7.13%) were found in high risk cancer families and 8 fragile sites in 1053 lymphocytes expression at 26 times (2.47%) were found in low risk cancer families. There was a significant difference between the two groups (P less than 0.01). In 46 fragile sites carried by 40 members of high risk cancer families, 27 were common, 5 rare, 12 provisional and 2 new fragile sites. Among them, the fragile sites at 1p22-p36 and 4q21-q31 were detected in members of high risk cancer families and in patients with esophageal cancer, meanwhile, uniform breakpoint in chromosome deletion and rearrangement was also found in 4 esophageal cancer cell lines. Therefore, the author conjectures that these fragile sites at 1p13-p36 and 4q21-q31 may be fragile site specific for high risk cancer families and patients with esophageal cancer, and they may be breakpoint-specific for esophageal cancer cells. These fragile sites may play an important role in esophageal carcinogenesis in high risk cancer families. PMID- 2249588 TI - [Biodistribution and radioimmunoimaging of monoclonal antibody to human lung adenocarcinoma in tumor-bearing nude mice]. AB - Biodistribution and radioimmunoimaging of monoclonal antibody, 5F11, against human lung adenocarcinoma (LTEP-a2) in tumor-bearing nude mice were studied. The binding rate of radioiodinated 5F11 with LTEP-a2, as determined by in vitro binding assay, was 27.64 +/- 5.01%, while the control was less than 5.0%, suggesting that 5F11 reacted specifically with LTEP-a2. Seventy-two, 96 and 120 hr after injection of 125I-5F11, the percentage of dose taken per gram tumor tissue was 4.84%, 6.29% and 6.60%, higher than those of all normal organs. From 48 to 120 hr on, the ratio of tumor to normal tissue (T/NT) in the liver, spleen, kidney, stomach and intestine was more than 2; T/NT in the lung was 3.1-4.7; T/NT in the blood increased gradually and was 1.87 at 96 after injection. Tumor location index was 4.16, while that of the normal tissue was only 1.21. These results showed that human lung adenocarcinoma xenografts in nude mice were specifically located by radioiodinated 5F11. Radioimmunoimaging was performed in tumor-bearing nude mice. The tumors were clearly visualized 72 hr after injection of 131I-5F11. Radioactivity was higher in tumor region than in other regions. The optimal imaging time was 72-96 hr after injection of radioiodinated 5F11. PMID- 2249589 TI - [Histochemical localization of glyco-conjugate and CEA-glycoprotein in human lung neoplasms]. AB - Sixty-six human lung neoplasms of different histological types and normal bronchial epithelial cells of newborn babies and adults were studied histochemically using ConA and PSA and the result was compared with that of CEA. Normal mucosal epithelium could bind to ConA, and the location of ConA receptors was related to the maturation of mucosal epithelial cells. Normal mucosal epithelium in adult bronchi failed to be stained with PSA and anti-CEA, and most of lung neoplasms could bind to PSA and positive for CEA, indicating that new glycoconjugate and CEA-glycoprotein could be synthesized after malignant transformation of mucosal epithelium. The binding of ConA, PSA and anti-CEA to cell membrane and nucleus membrane was characteristic of squamous cell lung cancer while lung adenocarcinoma mainly showed cytoplasmic staining. The weak staining of ConA, PSA and anti-CEA in small cell carcinoma and negative staining in carcinoid and malignant melanoma help testify that their origin may differ from that of squamous cell carcinoma and adenocarcinoma. PMID- 2249590 TI - [Invasion of mouse lung adenocarcinoma (LA795) cell aggregates transplanted into auricle of syngenic T739 mice]. AB - To evaluate invasion quantitatively and qualitatively in vivo, tumor cell aggregate invasion model was established. Mouse lung adenocarcinoma cell line (LA795) cells were allowed to form tumor cell aggregates after 3 days in a gyratory shaker culture system. LA795 cell aggregates, 0.3 mm in diameter, were transplanted subcutaneously to the auricles of syngenic T739 mice, which were then sacrificed at different intervals. Tumorigenicity was 100%. The process of invasion was divided into 5 stages: latent, proliferation, early invasion, mid and late invasion stages. In the mid and late invasion stages, cartilage and its capsule were invaded and progressively destroyed by tumor cells. Cartilage could be used as a criterion of judging invasion. Metastasis into the submaxillary lymph nodes (2/5) was found in the late invasion stage. The tumor cell aggregate invasion model is very useful in studying the invasion in vivo. PMID- 2249591 TI - [Morphological observation of destruction and phagocytosis of the target organs by human lung adenocarcinoma cell line in organ culture]. AB - In a co-culture system of human lung adenocarcinoma cells (LTEP-a2) with tissue fragments of human heart and liver, it was found that the target organs were destroyed with cancer cells invading. The destruction shown as cell swelling, atrophy, fatty degeneration and disappearance of the cardiac muscle streak, myocomma and local cell membrane, always occurred at sites immediately in contact with the invading cancer cells. However, cell changes could develop not in direct contact with tumor cells. The farther invasion by the tumor cells, the more serious destruction was seen. It was also observed that the tumor cytoplasmic processes could surround debris derived from the target tissue and the debris could be found inside cancer cells. The rapidly invading cells contained more phagosomes than the slowly invading ones. PMID- 2249592 TI - [Effect of plasma from normal individuals and lymphoma patients on immune function]. AB - The effect of plasma from 21 normal donors, 19 patients with non-Hodgkin's lymphoma and 11 patients with systemic lupus erythematosus (SLE) on interleukin 2 (IL-2) responsiveness, T cell proliferation and natural killer (NK) cell activity was studied. IL-2 responsiveness was enhanced by plasma from both normal and patients. The positive rate was 90.4% in normal, 89.5% in lymphoma and 90.9% in SLE, respectively. The same enhancing results were obtained in T cell proliferative assay. In contrast, effect of three kinds of plasma on NK cell activity showed inhibition. The inhibitory positive rate was 52.4% in normal, 36.8% in lymphoma and 81.8% in SLE, respectively. These results indicated that both enhancing and inhibitory effects on different immune functions showed certain specificity. The effect of plasmic substances on various immune responses is beneficial to the investigation of normal and abnormal immunoregulation. Furthermore, it is possible to isolate and purify these immunoregulatory substances as biological regulatory modifiers to modulate the abnormal immune functions. PMID- 2249593 TI - [Comparison of serum trace element spectrum of liver cancer patients and healthy adults]. AB - The contents of 15 trace elements in the sera of 30 liver cancer patients and 30 healthy adults were assayed by ICP-AES method. The data obtained were analysed by routine statistical tests, multi-variate discrimination analysis, multi-variate stepwise regression analysis and non-linear mapping algorithm. The results showed that the contents of copper, vanadium, cadmium, stannum, cobalt, nickel in liver cancer patients were significantly higher than those in healthy adults. The serum trace element spectrum of liver cancer patients was different from that of healthy adults. Hence, the liver cancer patients could be differentiated from healthy adults by serum trace element spectrum. PMID- 2249594 TI - [Ultrastructural study of fibrosarcoma]. AB - Ultrastructure of 9 cases of fibrosarcoma was observed and compared with that of fibrous connective tissue of 4 human embryos and 9 cases of spindle cell sarcoma, including 3 each of leiomyosarcoma, neurofibrosarcoma and dermatofibrosarcoma protuberans. Ultrastructurally, fibrosarcoma consisted of well-differentiated fibroblast-like cells, poorly differentiated fibroblast-like cells (embryonic fibroblast-like cells), myofibroblast-like cells and primitive mesenchymal cells. It is suggested that fibrosarcoma may arise from primitive mesenchymal cells which are capable of differentiating into fibroblast and myofibroblast. There were two special cases of fibrosarcoma in this series. One was a congenital fibrosarcoma with ultrastructure resembling adult and the other was a sarcoma of myofibroblast. Diagnosis and differential diagnosis between fibrosarcoma and leiomyosarcoma, neurofibrosarcoma, dermatofibrosarcoma protuberans are discussed. PMID- 2249595 TI - [Midline peripheral T-cell lymphoma--a disease entity recognized anew]. AB - Thirty-one cases of midline peripheral T-cell lymphoma (MPTL), treated during the past two years in our hospital, are reported. All were proven by immunohistochemical stain on frozen section, using a panel of antibodies: IIIC4 (CD5), Leu-2, Leu-3, Leu-4, T,p55, T11, Ia, Ki-1, IL2-R, B1/DAKO-CD22, Kappa, Lambda and IgM. Three cases were also stained with LCA, UCHL-1, MT1, MT2, MB1 and MB2 monoclonal antibodies in paraffin sections, and the results conformed with the frozen-sectionmethod. According to our present and previous reports, it is worthy of note that most of the so-called midline malignant reticuloses (MMR) in the past, including necrotic granulomatosis and malignant granulomatosis, are actually MPTL. In view of MPTL being highly malignant and not very rare in this country, it is emphasized that this disease should be paid more attention and recognized anew. More active treatment should be given to improve the results. PMID- 2249596 TI - [Surgical treatment of lung cancer with brain metastasis]. AB - Twelve cases of lung cancer with brain metastasis, which comprised 20% of all lung cancer patients complicated with brain metastasis in the same period in our hospital, underwent resection of both lung and brain lesions. There were 9 men and 3 women. The ages ranged from 29 to 65. The site of metastasis was supratentorial in 11 patients and on the right side in 8. The interval between thoracotomy and craniotomy was 18 days-5 years. There was no operative death. Six patients have survived for more than one year. Surgical approach to lung cancer with brain metastasis has proved to be better in comparison with other methods of treatment. Obviously, adjuvant therapy after surgery may play an important role in improving survival. Whether craniotomy or thoracotomy is first performed depends on the presence or absence of life-threatening neurological symptoms. If the patient's condition allows, the second operation should be performed as soon as possible. It is emphasized that in lung cancer patients, pre- and postoperative routine CT scan of the brain should be regularly done for early detection of brain metastasis. Meanwhile, a timely, planned, staged operation may improve survival. PMID- 2249597 TI - [Immunohistochemical and ultrastructural study on medullary carcinoma of the thyroid]. AB - Thirty seven cases of medullary carcinoma of the thyroid were studied by immunohistochemical technique and transmission electron microscopy (TEM). No amyloid deposit was observed in the tumor tissue in 6 cases. The monoclonal antibodies used were those directed to calcitonin, S-100, NSE and thyroid globulin. Their positive rates in the cancer cells were 100.0%, 45.9%, 64.9% and 16.2%, respectively. In the amyloid area, it was 89.3%, 25.0%, 35.7% and 14.2%. Many neurosecretory granules were found in the cytoplasm in 4/4 as observed by TEM. This study shows that the presence of calcitonin is of great value in establishing the diagnosis of medullary carcinoma. The results suggest that this tumor may arise from the parafollicular cells of the thyroid. PMID- 2249599 TI - [Female laryngocarcinoma--clinical analysis of 267 cases]. AB - Two hundred and sixty seven cases of female laryngeal carcinoma, treated in our hospital in the past 33 years, were analysed. The number of patients developed laryngeal cancer after menopause was 10 times as high as that developed before menopause. This suggests that a relating preponderance of male sex hormonal influence after menopause might be a contributing factor responsible for the high prevalence of laryngeal cancer in women. Another etiological factor was cigarette smoking. The pathological types and pattern of metastasis to cervical lymph nodes in the female laryngeal carcinoma were similar to those observed in male patients but superglottic cancer was more common than the glottic type. However, no significant difference in prognosis was observed between superglottic and glottic cancers. Provided indications are strictly adhered to, partial laryngectomy can give therapeutic results similar or even superior to total laryngectomy. PMID- 2249598 TI - [Bronchial arterial infusion chemotherapy with or without radiotherapy for advanced lung cancer]. AB - Forty-two patients with Stage III and IV advanced lung cancer received bronchial arterial infusion of Cyclophosphamide or Mitomycin in combination with Adriamycin and Cisplatin (CAP or MAP). Twenty-six patients were given radiotherapy too. Histologically, 16 had squamous cell carcinoma, 11 adenocarcinoma, 3 small cell anaplastic carcinoma and 1 un-classified cancer. Eleven were diagnosed by bronchial arterial radiography. The short-term results showed that complete response rate (CR) was 53.8% and partial response rate (PR) 38.5% in patients treated with combined chemotherapy and radiotherapy whereas in those treated with infusion chemotherapy, CR and PR were 0% and 81.3% respectively. PMID- 2249600 TI - [Comparative study of gray scale ultrasonography and radiography in diagnosis of gastrointestinal tract diseases]. AB - Thirty-seven cases of gastrointestinal (GI) tract diseases proven by operation and pathology were analysed according to gray scale ultrasonographic and radiographic manifestations and diagnoses. The authors consider that X-ray examination remains the first choice for detection of GI diseases; additional information may be obtained through sonography by displaying internal structure of the lesions, extent of tumor infiltration and metastasis if present. Sonography examination can supplement the roentgen findings. Therefore, combination of both methods will improve the accuracy of diagnosis of GI diseases. PMID- 2249601 TI - [Reconstructive operation of the gastric cardia with cardiectomy and ileo-colon replacement of the esophagus, stomach and cardia in gastric cardiac cancer]. AB - After having studied both the advantages and disadvantages of various reconstructive operations, an improved reconstructive operation, i.e. ileo-colon replacement of esophagus, stomach and cardia was performed to avoid regurgitation esophagitis after cardiectomy in gastric cardiac cancer. Twenty patients underwent such reconstructive operation. Clinical observation and measurement of intraluminal pressure in the upper digestive tract before and after operation showed that this kind of operation gave satisfactory short-term results, not only avoiding the regurgitation, but increasing the radical resection rate, reducing the other postoperative complications and improving the diet quantity intake also. This reconstructive operation is better than the traditional routine method and worthy of extensive use. Preparations before, during and after the operation, cooperation in manipulation during the operation are described. PMID- 2249602 TI - Nocturnal growth hormone surges in type 1 diabetes mellitus are both sleep- and glycemia-dependent: assessment under continuous sleep monitoring. AB - Our work has studied the relationship between nocturnal growth hormone (GH) surges, sleep and glycemia in seven conventionally treated type 1 diabetic patients under continuous sleep monitoring and the results were compared to those found in five age-matched healthy controls. On the experimental day, sleep was monitored from 24.00 to 07.00. Blood glucose levels and GH were assayed in both groups. As a group the diabetics had nocturnal GH responses higher than those in controls. However, the sleep-related GH release is not abnormally high in patients who maintain strict normoglycemia. Early-night hypoglycemia and/or rapidly decreasing blood glucose concentrations enhance sleep-related GH secretion in diabetics, whereas hypoglycemia not associated with slow-wave sleep (SWS) causes a moderate increase in GH. Late-onset nocturnal hypoglycemia is not potent enough to stimulate GH. It is proposed that in diabetics sleep-related GH production is probably not abnormally elevated within a wide range of stable glucose levels, but when these thresholds are crossed or when there is a rapid decrease in blood glucose, then GH secretion is inversely related to the changing blood glucose. Therefore, our study supports the conclusion that sleep-related GH secretion is finely modulated by the actual glycemic fluctuations in diabetic patients. PMID- 2249604 TI - Drug consumption in elderly subjects with occult fasting hyperglycaemia. AB - Drug consumption was studied in 87 persons with occult fasting hyperglycaemia and compared with sex- and age-matched non-diabetic controls all selected by screening a well-defined population aged 60-74 years. The daily use of prescribed and nonprescribed drugs was established by questionnaires and interviews. Sixty nine percent of subjects with fasting hyperglycaemia used drugs daily compared with 46% of controls (P less than 0.005). The difference was most pronounced among men. The median use of defined daily doses in those using drugs was not significantly different in the two groups. The main drug usage in both subjects with fasting hyperglycaemia and controls was in the cardiovascular medication group. More than half (59%) of the subjects with fasting hyperglycaemia used cardiovascular drugs compared with 27% of controls (P less than 0.0001). There were no significant differences in the other medication groups. Our results may reflect an increased morbidity from cardiovascular diseases among the elderly with occult fasting hyperglycaemia, and they seem to be comparable with the results on drug consumption found in the elderly with known diabetes. PMID- 2249603 TI - Characteristics of cranial nerve palsies in diabetic patients. AB - The incidence of palsy in the third, sixth and seventh cranial nerves was studied with regard to central nervous system involvement in diabetic patients. Among 1961 diabetic patients, 19 (0.97%) demonstrated cranial nerve palsies. Nine out of these 19 patients showed facial palsy; 6 palsy of the oculomotor nerve; 2 palsy of the abducent nerve; and 3 both oculomotor and abducent nerve palsies. In contrast, only 5 out of 3841 non-diabetic patients (0.13%) had any cranial nerve palsies; all 5 were cases of facial palsy. The incidence of cranial palsies in diabetic patients was significantly higher than that in non-diabetic patients (P less than 0.01). Concerning age, sex, the state of glycemic control, diabetic complications and method of treatment, there were no differences disclosed in the diabetic patients with cranial nerve palsy. The incidences of diabetic complications were compared between the patients with facial palsy and those with ophthalmoplegia. Only one out of 9 patients with facial palsy (11%) had diabetic complications, whereas 7 out of 10 patients with ophthalmoplegia (70%) demonstrated diabetic complications and the difference was significant. Thus ophthalmoplegia appears to be more closely related to diabetic metabolism while facial palsy is less strongly correlated with diabetes. PMID- 2249605 TI - Prevalence and clinical features of diabetes mellitus secondary to chronic pancreatitis in Japan; a study by questionnaire. AB - The prevalence and clinical features of diagnosed mellitus secondary to chronic pancreatitis (CP) were assessed from northern (Hokkaido) to southern (Okinawa) Japan by means of a questionnaire to elucidate whether WHO-classified malnutrition-related diabetes mellitus (MRDM) exists in Japan. Of a total 17,500 diabetic patients, only two (0.011%)-one fibrocalculous pancreatic diabetes (FCPD) and one protein-deficient pancreatic diabetes (PDPD) - exhibited MRDM characteristics. A total of 649 CP were collected and classified into 268 cases with chronic alcoholic pancreatitis (CAP), 150 cases with chronic calcified pancreatitis (CCP) and 231 cases with other CP. The prevalence of diabetes mellitus was found to be 50.7% in CAP, 72.7% in CCP and 22.8% in other CP. Among all diabetics, 56.6% was noninsulin-dependent (NIDDM) and 26.4% insulin-dependent (IDDM). IDDM was most frequent in CP. Satisfactory and less than satisfactory glycemic control was obtained in approximately three quarters of all subjects. Only one quarter showed poor glycemic control. Insulin treatment was frequent in CAP (52.2%) and CCP (61.7%), but less in other CP (27.5%). The prevalence of diabetic retinopathy was observed in 33.1% of all subjects, nephropathy 21.0% and neuropathy 36.3%, respectively. The prevalence of complications, including macroangiopathy tended to be higher in CAP and CCP (40.3 and 56.9%) than in other CP (31.4%). PMID- 2249606 TI - Side effects and indwelling times of subcutaneous catheters for insulin injections: a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus. AB - For 2 months we observed side-effects and indwelling times when using a subcutaneous catheter (Insuflon, Viggo AB, Sweden) for insulin injections. This method is used by approximately 600 children and adolescents with IDDM in Sweden today. 22 children and adolescents aged 4-19 years with a diabetes duration of 4.0 +/- 3.0 (mean +/- SD) years participated. Their HbA1c was 5.8 +/- 1.0%. All used 4-6 dosages of insulin per day. The catheter was placed subcutaneously in the abdominal wall, and replaced by parents when home tests showed increased blood or urine glucose, when the child experienced pain or when skin changes were observed. The 22 patients used 239 catheters with a mean time between changing catheters of 4.8 +/- 2.2 (range 0.5-17) days (= 1147 catheter days). Noted side effects were (% of catheter days): fixation problems, 5.6%; minor infection/irritation (= redness greater than 1 mm), 5.6%; pain, 2.8%; sore skin from plastic wings, 2.4%; itching/dry skin, 2.0%; eczema from band-aid, 1.7%; blocked catheter/injection needle, 1.6%; leakage of insulin, 1.3%, transient lipohypertrophies, 1.1%; hematoma/blood in catheter, 0.8%, and moist skin, 0.3%. No major infections requiring surgical or antibiotic treatment occurred. In conclusion, the use of indwelling insulin catheters seems to be a safe method to lessen the pain of insulin injections with a low frequency of side effects. The long-term metabolic control was not altered in this group of well-controlled children. We therefore find that we can recommend the use of indwelling catheters to children and adolescents who have difficulties with injections because of needle phobia or pain, particularly when using MIT. PMID- 2249607 TI - The ExacTech blood glucose testing system. AB - The ExacTech system, a new device for home measurement of blood glucose was tested in the laboratory, in the out-patient clinic, and by diabetic patients. The system is based on an electrochemical principle, and consists of specially impregnated strips and a small, pencil-shaped meter. (1) Six meters were tested in the laboratory at blood glucose concentrations of 4, 10 and 20 mmol/l. Low coefficients of variation were found at 10 and 20 mmol/l, but those at 4 mmol/l were rather high (approximately 10%). Analysis of variances showed no difference in the between and the within variation of the meters. (2) The blood glucose concentrations of 50 consecutive out-patients were determined by the ExacTech system and a standard laboratory method. Correlation analysis showed an r value of 0.95 (P less than 0.001). (3) The results obtained by 13 patients repeating the correlation experiment were in agreement with the second part of the study. The ExacTech system is very simple to operate by the patients, and can be recommended for home monitoring of blood glucose. PMID- 2249609 TI - Volume-conducted or "far-field" compound action potentials originating from the intrinsic-hand muscles. AB - When a recording electrode is situated at a relatively far and roughly equal distance from multiple muscle action potential (MAP) sources such as the intrinsic-hand muscles (far-field recording), the individual MAPs generated by muscle fibers may contribute to the resultant compound potential with nearly equal weights depending on the orientation of the individual MAP fields. This is in contrast to recording MAPs directly over the muscle (near-field recording), in which the resultant potential primarily reflects the MAPs that were near the recording electrode. Far-field recorded compound MAPs(CMAPs) thus may provide another dimension or perspective into viewing the overall spatio-temporal relationship among MAPs generated by a large number of muscle fibers. In this study, we described CMAPs from intrinsic-hand muscles that were recorded at a distance from their potential sources. PMID- 2249608 TI - Effect of prolonged hyperinsulinaemia on adipocyte insulin binding and action in normal man. AB - Prolonged moderate insulinaemia over 20 h in normal humans produces a significant reduction of in vivo insulin action. To examine the effects in man of such moderate hyperinsulinaemia on in vitro glucose metabolism, insulin-receptor binding, glucose transport and incorporation of glucose into lipid were determined in adipocytes isolated from paired gluteal fat biopsies, taken from six normal human volunteers before and 1 h after 20 h of exogenous hyperinsulinaemia (plasma insulin 38 +/- 3 mU/l). Specific binding of insulin to isolated adipocytes was not altered (6.7 +/- 0.7 versus 7.6 +/- 1.5% per 10(5) cells). Basal glucose transport of 3-O-[14C]methylglucose in the absence of insulin was reduced after hyperinsulinaemia (5.2 +/- 1.1 versus post 4.3 +/- 1.3 pmol/7 s per 10(5) cells, 0.1 less than P greater than 0.05; or expressed as percent of maximal response: 60 +/- 5 versus post 49 +/- 1%, P less than 0.05), but maximal transport (9.2 +/- 1.5 versus post 8.7 +/- 1.5 pmol/7 s per 10(5) cells) and ED50 (87 +/- 17 versus 67 +/- 15 pmol/l) were unchanged. Conversion of glucose into lipid, using 3-D-[3H]glucose, was unchanged basally, at maximal response or ED50 of the dose response curve. In conclusion, moderate 20 h in vivo hyperinsulinaemia in normal humans induces only a small change in basal vitro adipocyte glucose transport, and no change in insulin-receptor binding or in vitro incorporation of glucose into lipid. These data suggest that the adipocyte does not contribute to the impaired insulin action produced by in vivo moderate hyperinsulinaemia in man. PMID- 2249611 TI - Comparison of stretch reflex activities and reaction times in two separate age groups of human subjects. AB - The effect of prior instruction on stretch reflex activity was compared in two separate age groups of healthy subjects. No clear differences were found for amplitude modulation and reaction items between the younger (25.6 +/- 3.2 years) and the older group (56.6 +/- 6.5 years) of subjects. A significant difference was observed in the absolute magnitudes of the background activity, short latency and long latency reflex activities which were higher in the older group of subjects than in the younger subjects. PMID- 2249610 TI - Electromyographic reflexes evoked in human flexor carpi radialis by tendon vibration. AB - The rectified, electromyographic (EMG) reflexes evoked in the voluntarily contracting flexor carpi radialis (FCR) muscle by vibration of its tendon were studied in healthy human subjects. Responses comprised a prominent, transient, short-latency (SL, 20-25 ms) increase in EMG, attributed to Ia mono- and/or oligo synaptic action, followed by a series of less pronounced troughs and peaks of activity. Evidence of continuing Ia mono- or oligo-synaptic action was indicated by (i) the presence of small subpeaks, at vibration frequency, superimposed upon the excitatory components and (ii) the occurrence of a separate reduction in EMG, of consistent latency (ca. 30 ms), after cessation of stimulation. Progressively shortening the train of vibration from 29 cycles (at 145 Hz) to a single cycle significantly reduced net, excitatory reflex activity. Gradually increasing the level (10-50% maximum) of pre-existing voluntary contraction on top of which reflexes were elicited, by moderately prolonged (29 cycles) trains of vibration, resulted in small increases, in absolute terms, in SL peaks and in later, excitatory EMG activity. Excitatory reflexes, when normalised for pre-stimulus EMG, however, declined in an approximately hyperbolic manner with increasing background activity over this range. Thus, effective "automatic gain compensation" does not operate for vibration reflexes in FCR. PMID- 2249612 TI - Modulation of stretch activity with instruction. PMID- 2249613 TI - Cryptogenic hemifacial spasm. A neurophysiological study. AB - Whether hemifacial spasm (HFS) is due to axono-axonal ephaptic transmission or to facial nucleus abnormal hyperexcitability remains controversial. The neurophysiological hallmark of HFS is the delayed response (DR). This response has an indirect pathway and thus a long latency. It is evoked A) as a distant response in muscles innervated by a facial branch other than the one stimulated, and B) in muscles innervated by the branch stimulated. In this work, 99 single all-or-none DRs of 24 cases of cryptogenic HFS were studied by threshold stimulation of a branch, or of the trunk, of the facial nerve. A) Eighty-eight distant DRs were studied. Fifty-four of them were frequently evoked as double discharges (DDs), or sometimes as multiple discharges, with a 3 to 7 ms interval. A collision technique, using paired stimuli, showed that the second discharge of 12 out of 20 DDs was accompanied by a back-wave due to a proximal ectopic re excitation on the axon, or to the back-firing of an alpha cell (F-response), or to both. F-waves in HFS were more frequent than in normals or in other facial pathologies. B) Eleven DRs were recorded in muscles innervated by the facial branch stimulated. Some of them persisted when, using a stronger stimulus, the same all-or-none potential was also evoked as a direct response. In other cases both the direct response and the DR were evoked with identical stimulation threshold. The direct-indirect response interval of these 11 DRs was shorter than the normal M-F interval. These findings suggest that, in the case of HFS, axons are interconnected by uni- and bidirectional ephapses. Self-sustained repetitive firing in such a group of axons apparently results from re-excitations occurring both at the ephapse site and at the cellular level (F-responses). Spasm develops when several groups fire together. The changing excitability of the alpha cells modulates the importance of the phenomenon. PMID- 2249614 TI - Determination of peak-ratio by digital turns-amplitude analysis on line. AB - In a previous study the peak-ratio of turns to mean amplitude of the EMG interference pattern obtained from tape recordings identified 80% of patients with myopathy. In order to obtain the peak-ratio during the examination using the mean amplitude as an indication of force a digital turns-amplitude computer with a TMS 320/10 digital signal processor was developed. The EMG was analysed with a 12 bit resolution and a sampling rate of 100 kHz. In 492 samples from the brachial biceps muscle of controls, patients with myopathy and neuropathy, the digital method gave about the same turns-amplitude values as the analogue analyser. Control material for on line analysis of the peak-ratio was obtained in the brachial biceps, the abductor pollicis brevis, the medial vastus and the anterior tibial muscles of 20 subjects. PMID- 2249615 TI - Chronic inflammatory demyelinating polyneuropathy as first manifestation of human immunodeficiency virus infection. AB - We studied three patients who were admitted to the hospital because of progressive weakness without other systemic signs or symptoms. All three cases were young males who had been intravenous drug user for many years. Electrophysiologic study showed prolonged distal latencies and marked slowing of motor and sensory conduction velocities, consistent with primary demyelination. Nerve biopsy also showed signs of demyelination. Antibodies against HIV in CSF and blood were detected during the diagnostic evaluation. Clinical and electrophysiological studies improved in two cases after prednisone administration. Patients with predominant motor demyelinating neuropathies and risk factors should be screen for HIV infection. PMID- 2249616 TI - Returning to the roots of endocrinology: the challenge of evaluating in vivo glandular secretory activity. PMID- 2249617 TI - Localization of immunoreactivity for calcitonin gene-related peptide in the rat anterior pituitary during ontogeny and gonadal steroid manipulations and detection of its messenger ribonucleic acid. AB - Localization of calcitonin gene-related peptide (CGRP) expression in the rat anterior pituitary and its changes during ontogeny and after gonadal steroid manipulations were studied by immunocytochemistry, RIA, and in situ hybridization. Colocalization studies and the combined use of immunocytochemistry and in situ hybridization revealed that CGRP immunoreactivity is localized mainly in gonadotropes and alpha- and beta-CGRP messenger RNAs were detected in CGRP immunoreactive cells. Immunoreactivity for CGRP also was detected in nerve fibers and colocalized with substance P immunoreactivity. Cells immunoreactive to CGRP antiserum were first detected in fetal rats at gestational day 18, and the incidence considerably increased between postnatal days 5 and 14. CGRP immunoreactivity was low in control adults of both sexes and in pregnant and ovariectomized females but increased in lactating, estrogen-supplemented ovariectomized and high-dose estrogen-treated females, and in high-dose estrogen treated and castrated males. Testosterone supplement suppressed the effect of castration on CGRP immunoreactivity in males. Quantities of extractable immunoreactive CGRP under conditions of estrogen manipulation corresponded well to the immunocytochemical findings (females: controls, 96.4 +/- 13.1 fmol/gland; ovariectomized, 107.6 +/- 19.2; high-dose estrogen-treated, 212 +/- 23.0; estrogen-supplemented ovariectomized, 680 +/- 42.1). The present study suggests that pituitary CGRP is synthesized and stored in gonadotropes, is modulated by gonadal steroids, and may have a functional link with gonadotropins. PMID- 2249618 TI - The effects of parathyroid hormone (PTH) and PTH-related peptide on osteoclast resorption of bone slices in vitro: an analysis of pit size and the resorption focus. AB - The mechanism whereby PTH, a potent stimulator of bone resorption, may under certain circumstances exert anabolic effects on bone is not known, but it is possible that it involves reduction of the size of osteoclast resorption lacunae. We have therefore made a detailed in vitro study of the effects of PTH and PTH related peptide (PTHrP) on resorption by neonatal rat osteoclasts paying particular attention to the plan area of resorption pits. In order to distinguish between increased resorption at a particular site and increased numbers of sites, we have used an eyepiece graticule to define a focus of resorption, namely an area occupying 1/116th of the bone slice, which may contain either one or several pits. In addition we have studied the relationship between the number of pits in a resorption focus and the total area of bone resorbed at the focus. We found that PTH and PTHrP, at doses between 2 x 10(-10) M and 2 x 10(-8) M, while exerting significant stimulatory effects on bone resorption, caused a reduction in the median plan area of pits. An increase in the number of resorption foci was the primary stimulatory effect of PTH and PTHrP, occurring within 6 h in the case of PTH. However, the plan area of bone resorbed at a focus showed no significant increase, despite an increase in the number of pits per focus, because as more pits were formed at a focus, the pits were smaller, thus partially dissipating the stimulatory effect of PTH on resorption. These results are consistent with the activation of new remodeling sites by PTH in vivo. Furthermore, the formation of smaller pits under the resorptive influence of PTH may, together with the maintenance of coupling between formation and resorption, play a role in the preservation of cancellous bone recorded in cases of primary hyperparathyroidism and the anabolic effect of exogenous PTH. PMID- 2249619 TI - Pro-gonadotropin-releasing hormone (ProGnRH) and GnRH content in the preoptic area and the basal hypothalamus of anterior medial preoptic nucleus/suprachiasmatic nucleus-lesioned persistent estrous rats. AB - The content of GnRH and its precursor peptide were quantified in female rats bearing lesions in the anterior medial preoptic nucleus (AMPO) and the suprachiasmatic nucleus (SCN), and the effects of the lesions on the synthetic activity of the GnRH neurons were evaluated. Electrolytic lesions which induced persistent estrous (PE), or irregular estrous cycles, were produced by passing 5 10 microA of direct current into the AMPO or the SCN of female rats which exhibited regular 4 days estrous cycles before the lesions. Approximately 5 weeks after lesion placement, blood samples were withdrawn from catheterized, freely moving animals and plasma LH, PRL, estrogen, and progesterone were determined by RIA. The preovulatory surges of LH and PRL were eliminated in AMPO- or SCN lesioned PE rats. Moreover, the LH surge was eliminated and the PRL surge significantly attenuated after estrogen and progesterone treatment of rats bearing complete lesions, irrespective of the presence of ovaries. Irregular cycling animals with incomplete AMPO or SCN lesions, exhibited attenuated LH surge and PRL surge similar to proestrous controls. In one incidence this occurred spontaneously, and could also be induced by sequential estrogen and progesterone injections. After ovariectomy, plasma LH levels were significantly lower in the lesioned animals as compared to sham operated rats (P less than 0.05). Similar secretory patterns of LH and PRL were obtained from a second series of sham-operated rats during the different stages of the estrous cycle or from AMPO- or SCN-lesioned rats during persistent estrus. After 2 months the animals were killed between 0830 and 0930 h, and the preoptic area and the basal hypothalamus were microdissected from the brain sections. After extraction and purification, proGnRH and GnRH levels were measured by RIA. ProGnRH levels in the preoptic area were significantly reduced in AMPO- or in SCN-lesioned rats, compared to proestrous controls (P less than 0.01). In contrast, GnRH levels in either area did not differ in AMPO- or in SCN-lesioned animals compared to sham operated, proestrous controls. Therefore, lesions of the AMPO or the SCN produce PE and reduce proGnRH without reducing GnRH levels. These data would suggest that the AMPO and the SCN participate in the control of the estrous cycle and are necessary for preovulatory surges of PRL and LH to occur and that the AMPO and the SCN form part of the neural circuit that regulates GnRH synthesis and/or release. PMID- 2249620 TI - Restoration of thyroid function after total thyroidectomy and quantitative thyroid cell transplantation. AB - Quantitative thyroid cell transplantation was used to evaluate the reestablishment of thyroid function in surgically thyroidectomized rats. Donor thyroid glands were enzymatically dispersed, and the cells were quantified, serially diluted, and inoculated into the sc fat pads of syngeneic recipient rats 1 day after surgical thyroidectomy. Blood samples were obtained weekly, and serum T3, T4, and TSH levels were determined by RIA. Recipient rats displayed different patterns of restoration of thyroid function depending on 1) the number of thyroid cells inoculated and 2) their dietary iodine intake. We observed cell dose dependent differences in both the rapidity and extent of thyroid function after cell transplantation. Recipients fed a normal diet and grafted with 6 x 10(4) or more cells reached near-normal levels of all three hormones. In recipients fed a low iodine diet, T4 and TSH levels remained at significantly hypothyroid levels for the duration of the 7-week study. At the highest cell dose examined (3 x 10(5)), however, serum TSH levels began to decline by the sixth to seventh week. In spite of the iodine deficiency, recovery of T3 levels in these recipients paralleled that in recipients fed normal diets. Intact control animals exhibited the anticipated pattern of decreased T4, increased TSH, and essentially unchanged T3. 125I uptake by the grafts was also dependent on the initial number of thyroid cells grafted independent of diet. PMID- 2249621 TI - Glucose transporter in insulin sensitive tissues of lean and obese mice. Effect of the thermogenic agent BRL 26830A. AB - Glucose transport is decreased in skeletal muscle and adipose tissues of obese, hyperglycemic, insulin-resistant animals. Here we have characterized the glucose transporter(s) in muscle and adipose tissues from normal and obese mice, and we have studied the effect of a treatment with the thermogenic agent BRL 26830A. Glucose transporters were examined in crude tissue membrane fractions (microsomal + plasma membranes) by Western blot analysis using antipeptide antibodies specific for the erythroid (Glut 1) or muscle/fat (Glut 4) glucose transporters. In these insulin sensitive tissues, only Glut 4 was detected. In membranes from obese animals, the Glut 4 number was decreased by 40% +/- 4% in brown adipose tissue (mean +/- SEM of 9 preparations, P less than 0.001), whether the results were expressed per total tissue or per mg of protein. By contrast, Glut 4 number was unchanged in skeletal muscle. In white adipose tissue of obese animals, Glut 4 number per total fat pad was increased. However, due to the enlarged fat pad size, Glut 4 content was diminished when expressed per mg of white adipose tissue membrane protein in obese compared to lean animals. After a 18 day-treatment with BRL 26830A (1 or 2 mg/kg.day), glycemia of obese mice, which was slightly elevated compared to lean animals, was normalized, while insulinemia remained markedly above control values. In brown adipose tissue, the total number of Glut 4 returned to normal at 1 mg of the drug, or increased by 63% +/- 14% at 2 mg. Since membrane protein content was increased by the treatment, when results were expressed per mg of membrane protein, Glut 4 was similar in lean and BRL 26830A (1 or 2 mg) treated obese mice. BRL 26830A treatment did not modify Glut 4 in skeletal muscle, and it increased Glut 4 number in white adipose tissue in a dose dependent manner. In conclusion, in obese mice, the glucose transporter number was reduced mainly in brown adipose tissue, a defect which could contribute to the hyperglycemic syndrome. Treatment with the thermogenic agent BRL 26830A normalized in parallel glycemia and glucose transporter number in brown adipose tissue, suggesting that this tissue could play a role in glucose homeostasis in rodents. PMID- 2249622 TI - Purification and characterization of bovine placental retinol-binding protein. AB - A major low mol wt acidic protein, 3B3, produced from cultures of day 29-90 bovine allantoic membranes (in the presence of [3H]leucine or [35S]methionine) and from day 29-60 allantoic fluid, has been purified. The protein consisted of three isoelectric variants (pI 5.3-6.1) of identical mol wt (23,200 +/- 900) when analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino-terminal sequence analysis of 3B3 isolated from allantoic fluid on the first 43 amino acids showed that 3B3 had 93% and 91% homology with rabbit and human plasma retinol-binding protein (RBP), respectively. The UV absorption spectrum and the fluorescence excitation and emission spectra of purified 3B3 from both sources indicated the presence of bound retinol. Rabbit antiserum was raised against placental RBP (3B3) isolated from allantoic membrane culture medium. Placental RBP was immunoprecipitated from radiolabeled allantois and chorion culture medium and was detected in allantoic membrane culture medium and allantoic fluid by Western blotting. These results suggested that bovine placental membranes secrete RBP into allantoic fluid and that placental RBP may play important roles in vitamin A metabolism in the developing embryo. PMID- 2249623 TI - Isolation of a hepatic iodothyronine 5'-monodeiodinase by nondenaturing agarose gel electrophoresis. AB - We have examined the application of nondenaturing agarose gel electrophoresis for isolation of the catalytically active iodothyronine 5'-monodeiodinase (5'-MD) in rat liver microsomes. Preliminary studies showed that most ingredients of conventional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, including acrylamide, SDS, and bromophenol blue, markedly inhibited 5'-MD activity in solubilized rat liver microsomal proteins (SRLMP). We replaced these inhibitory components with those that had little or no inhibitory effect on the 5'-MD and devised conditions for nondenaturing agarose gel electrophoresis for isolation of a 5'-MD protein. SRLMP (up to 120 micrograms protein/well), prepared by preincubation with 5 mM 3-[(3-cholamidopropyl)dimethylammonio 1 propanesulfonate] (CHAPS) and 1% 2-mercaptoethanol, were subjected to electrophoresis in 0.35% agarose gel in 20 mM Tris-HCl, 10 mM EDTA, pH 6.6 buffer containing 2 mM CHAPS and 1 mM thioglycolic acid. Electrophoresis was carried out for 14 h at 4 C using 2.5 V/cm. After phoresis, the gel was sliced into 16 fractions, and homogenates of each fraction were tested for 5'-MD activity by incubation with 0.6 nM [125I]rT3 for 30 min at 37 C in the presence of 10 mM dithiothreitol. The peak 5'-MD activity was detected in fraction 6 (Rf, 0.375). This fraction accounted for about 30% of total 5'-MD activity and only 6% of protein in the gel. The gel slice containing the peak 5'-MD activity was next subjected to a second electrophoresis at pH 7.6 for 4 h in a 90 degrees different direction. The most 5'-MD activity was demonstrated in the third of 8 gel fractions. SDS-polyacrylamide gel electrophoresis of this fraction demonstrated only one 55 K protein in most experiments and occasionally an additional 35 K protein. The specific activity of 5'-MD in this fraction of greater than 11 pmol I-/mg protein.h was at least 2.3-fold that in SRLMP. Rabbits were immunized with agarose gel containing the peak 5'-MD activity. Immunized rabbit immunoglobulin G bound up to 70% of 5'-MD activity in SRLMP, and the binding effect varied in a dose-dependent manner. Western blot analysis revealed that the anti-5'-MD antibody bound only one 55 K protein among innumerable proteins in SRLMP. A specific antiprotein disulfide isomerase antibody bound a slightly larger, 57 K protein in SRLMP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249624 TI - Vanadate augments insulin binding and prolongs insulin action in rat adipocytes. AB - Vanadate has been documented to inhibit tyrosine phosphatase activity and to have insulin-mimetic effects. However, oral administration to hypoinsulinemic diabetic rats in vivo lowers blood glucose at serum concentrations of vanadate that have minimal insulin-like effects in vitro. We, therefore, investigated the effect of low concentrations of vanadate on insulin binding, processing, and action. Preincubation of rat adipocytes for 2 h at 37 C with 10-200 microM vanadate resulted in a dose-dependent increase in [125I]insulin binding at 37 C to a maximum of 45% above the control value. Total cell-associated radioactivity and internalized (acid-resistant) hormone were similarly increased. Binding studies at 15 C in the presence of potassium cyanide revealed that this effect was associated with an increase in insulin receptor affinity. Consistent with these results, vanadate affected binding at 37 C only at low concentrations of insulin. Preloading adipocytes for 8 min with 0.4 ng/ml [125I]insulin revealed that vanadate slowed the rate of release of internalized hormone (50% release; 9.0 min vs. 12.5 min). The proportion of [125I]insulin released in intact form (trichloroacetic acid precipitable) was significantly increased by vanadate up to 15 min. Preincubation of adipocytes with vanadate resulted in an apparent increased sensitivity, with a shift to the left in the dose-response curve of insulin-stimulated lipogenesis (ED50, 0.2 vs. 0.08 ng/ml). Furthermore, vanadate maintained maximum insulin-stimulated lipogenesis after extensive washing to remove insulin. These effects could not be accounted for by the insulin-mimetic effect of vanadate alone. We conclude that 1) low concentrations of vanadate (less than 200 microM) increase insulin receptor affinity and consequent insulin uptake in rat adipocytes; 2) the excess cell-associated insulin exists largely as intact hormone; and 3) the increased binding at low insulin concentrations results in an apparent increase in insulin sensitivity. Vanadate at low concentrations also prolongs insulin action. Whether tyrosine phosphatase inhibition is the basic biochemical mechanism remains to be determined. PMID- 2249625 TI - Rapid effects of 1,25-dihydroxyvitamin D3 and extracellular Ca2+ on phospholipid metabolism in dispersed porcine parathyroid cells. AB - We examined the rapid effects (less than 120 sec) of 1,25(OH)2D3 on membrane phospholipid hydrolysis in porcine parathyroid cells and compared these effects to those produced by extracellular Ca2+. Cells were labeled with [3H]myo-inositol or [14C]arachidonic acid for 3 h, then exposed to various 1,25(OH)2D3 concentrations in 0.5 mM Ca2+ for different time periods or to 2 mM [Ca2+]. Parathyroid cells showed a biphasic increase in diacylglycerol (DAG), monoacylglycerol (MG), phosphatidic acid (PA), and inositol trisphosphate (IP3) in response to 1,25(OH)2D3 (10(-12)-10(-8) M) or to 2 mM [Ca2+]. This effect was rapid (within 5 sec) and dose-dependent, with a maximal stimulation with 10 pM of 1,25(OH)2D3. At this concentration, the first peak of DAG, MG, and IP3 was at 5 sec and reached 176 +/- 9%, 134 +/- 4%, and 154 +/- 13%, respectively vs. basal levels. For PA, the first maximum increase was at 20 sec (130 +/- 6%). At 30 sec MG, PA, and IP3 returned to basal levels, whereas the decrease in DAG was under the basal level (-25 +/- 5%). The second peak reached a maximum at 60 sec for the four products (145 +/- 8%, 119 +/- 5%, 125 +/- 6%, and 175 +/- 20%, respectively) then decreased to basal level at 120 sec. High extracellular Ca2+ (2 mM) and fluoride (5 mM) also produced similar increase in phosphatidylinositol metabolites, except that DAG levels returned to basal level at 30 sec. In conclusion, the present data shows the existence of rapid effects of 1,25(OH)2D3 in porcine parathyroid cells. The short time sequence suggests that they are mediated by a direct interaction with the membrane, possibly through a receptor mediated process linked to phospholipase C by a G-protein. PMID- 2249626 TI - Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus. AB - Considerable evidence shows that gonadal steroids exert a facilitatory influence on levels and release of neuropeptide-Y (NPY) from the hypothalamus. However, it is not known whether gonadal steroids act directly on NPY-producing cells in the arcuate nucleus (ARC) of the hypothalamus to produce these facilitatory effects on NPY or whether they act on other cells that have a modulatory influence via synapses on ARC NPY cells. We applied the combined method of steroid autoradiography and immunocytochemistry to assess the localization of [3H]estradiol in relation to NPY-producing cells in the hypothalamus. Rats (n = 6) were bilaterally ovariectomized and injected intracerebroventricularly with colchicine. Twenty-four hours later each rat received an iv injection of 17 beta [2,4,6,7,16,17(-3)H]estradiol (SA, 166 Ci/mmol) at a dose of 5.0 micrograms/kg BW. One hour after the injection of [3H]estradiol, the rats were perfused with 4% paraformaldehyde; brains were removed, frozen in isopentane precooled in liquid nitrogen (-190 C), sectioned, and processed for autoradiography. The autoradiograms were then incubated with specific antibodies for NPY immunostaining by the avidin-biotin-peroxidase method. The results revealed NPY immunopositive cells in the ARC, striatum, hippocampus, amygdala, and cerebral cortex and a few cells in the median eminence. NPY-immunoreactive fibers were also detected in the internal layer of the median eminence. The largest number of neurons showing NPY immunoreactivity in the cytoplasm was detected in the ARC, and only in this nucleus did we observed colocalization of [3H]estradiol and NPY immunoreactivity in neurons. A population of NPY-immunopositive cells in the ARC (10-20%) exhibited nuclear [3H]estradiol; the majority of these cells were located in the lateral and ventral portions of the ARC. Since gonadal steroids stimulate hypothalamic NPY levels and release, this anatomical evidence of colocalization is suggestive of a direct genomic modulation of NPY neurosecretion by steroids in a subpopulation of hypothalamic NPY-immunopositive neurons. PMID- 2249627 TI - A simple and sensitive microtiter plate estrogen bioassay based on stimulation of alkaline phosphatase in Ishikawa cells: estrogenic action of delta 5 adrenal steroids. AB - We have developed an estrogen bioassay using the Ishikawa human endometrial adenocarcinoma cell line growing in 96-well microtiter plates. Alkaline phosphatase enzyme activity (AlkP) in these cells is markedly stimulated by estrogens, and this enzyme can be easily quantified in situ using a chromogenic substrate. These cells are very sensitive to estrogens; estradiol induces AlkP at levels as low as 10(-12) M. Antiestrogens completely block the action of estradiol. Various estrogens stimulate AlkP with potencies comparable to those achieved in vivo. The induction of AlkP is specific for estrogens; no other type of steroid, including androgens, progestins, mineralocorticoids, or glucocorticoids produce this effect. The stimulation of AlkP in Ishikawa cells is specific for estrogens, is highly reproducible and sensitive, and permits large numbers of samples to be assayed with ease. We have used this assay to investigate the estrogenic action of the adrenal delta 5-3 beta-hydroxysteroids. While pregnenolone is inactive, dehydroepiandrosterone and its sulfate ester induce AlkP slightly. However, the C19 steroid, 5-androstene-3 beta, 17 beta-diol is considerably more estrogenic in this assay, although it stimulates Ishikawa AlkP with a potency of 1/30,000 that of estradiol. The stimulation by 5 androstene-3 beta,17 beta-diol is inhibited by antiestrogens, but it is not blocked by the delta 5-3 beta-hydroxysteroid isomerase/dehydrogenase inhibitor, cyanoketone, or by the aromatase inhibitor, 4-hydroxy-androstenedione. Thus, neither conversion to a delta 4-3-ketone nor aromatization is required for the action of this unusual estrogen. PMID- 2249628 TI - pH-dependent stimulation of peptidylglycine alpha-amidating monooxygenase activity by a granule-associated factor. AB - Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a granule associated enzyme that catalyzes the production of alpha-amidated peptides from their glycine-extended precursors, a posttranslational modification often required for full biological activity. PAM activity in crude homogenates of bovine neurointermediate pituitary has an acidic pH optimum for the peptide substrate alpha-N-Ac-Tyr-Val-Gly. During purification, the pH optimum shifts, so that purified bovine (b)PAM exhibits an alkaline pH optimum for this substrate with virtually no activity below pH 6.5. A factor that restores the ability of purified bPAM to produce alpha-amidated products at pH 6 was identified. In rat anterior pituitary this factor (denoted SPAM for stimulator of PAM activity) was a soluble protein with a mol wt of 44 K by gel filtration; its stimulatory activity could be reduced or eliminated by trypsin digestion or boiling. SPAM stimulated PAM activity at acidic pH by increasing the apparent Vmax and decreasing the apparent Michaelis-Menten constant (Km) for the peptide substrate. Like PAM, SPAM activity is localized to the secretory granule. Levels of SPAM activity in various rat tissues correlated closely with levels of PAM activity, with the greatest amount of SPAM activity in atrium, anterior pituitary, and neurointermediate pituitary. The distribution of PAM and SPAM between soluble and membrane fractions also correlated closely. In AtT-20 cell lines transfected with a complementary DNA (cDNA) encoding the full-length bPAM precursor, both SPAM and PAM activities were increased compared to wild type cells; both activities were decreased in a cell line expressing an antisense rat (r)PAM mRNA. In marked contrast, an AtT-20 cell line transfected with a cDNA encoding a truncated, soluble form of bPAM had elevated levels of PAM activity, but levels of SPAM activity were not increased compared to wild-type cells. These results suggest that SPAM activity is closely linked to the expression of full-length PAM. The interaction of PAM and SPAM may represent a site for regulation of the synthesis of bioactive peptides, particularly at low intragranular pH. PMID- 2249629 TI - Transforming growth factor-beta 1 inhibits ovarian androgen production: gene expression, cellular localization, mechanisms(s), and site(s) of action. AB - It is the aim of this study to establish ovarian transforming growth factor-beta 1 (TGF beta 1) gene expression, to reevaluate its cellular localization, and to explore potential interactions of this regulatory peptide on ovarian androgen biosynthesis. Northern analysis of whole ovarian polyadenylated RNA revealed a single 2.5-kilobase transcript corresponding to the TGF beta 1 precursor. Immunohistochemical staining localized the protein to the thecal-interstitial (interfollicular) compartment. To explore potential autocrine effects of TGF beta 1, use was made of whole ovarian dispersates from immature rats the differentiation of which was monitored by the acquisition of androgen biosynthetic capacity. The accumulation of androsterone, the major androgenic steroid detectable in this culture system, increased 5.4-fold over baseline in response to treatment with hCG (1 ng/ml). This effect was further optimized (2- to 4-fold) by supplementation with insulin (1 microgram/ml) and insulin-like growth factor-I (50 ng/ml). In the absence of these optimizing supplements, TGF beta 1 (10 ng/ml) was without effect on basal androsterone accumulation, producing distinct, albeit relatively limited (25%), inhibition of hCG hormonal action. In contrast, supplement-mediated optimization of ovarian androgen biosynthesis revealed TGF beta 1 to be a highly potent inhibitor (greater than 80%) of hCG hormonal action. This reversible TGF beta 1 action proved time and dose dependent, with a minimal time requirement of 72 h and a median inhibitory dose of 2.6 ng/ml. TGF beta 1 action was not due to diminution in the viable cell mass or altered cAMP generation and, therefore, most likely involved a site(s) of action distal to or independent of cAMP generation. Cellular radiolabeling studies of TGF beta 1-treated ovarian cells disclosed the accumulation of steroid intermediates proximal to the 17 alpha-hydroxylation step, suggesting TGF beta 1 mediated blockade at the level of the steroidogenic enzyme 17 alpha hydroxylase/17-20-lyase. Taken together, these observations are in keeping with the view that TGF beta 1, possibly of thecal-interstitial origin, may not only play a positive paracrine role at the level of the adjacent granulosa cell (as previously reported), but may also constitute one of several autocrine signals concerned with the regulation of ovarian androgen economy. As such, these findings reaffirm the polyfunctional nature of TGF beta 1 action, as manifested by its diametrically opposed effects in different ovarian compartments. PMID- 2249630 TI - Functional coupling of neonatal rat Sertoli cells and gonocytes in coculture. AB - Interaction between Sertoli cells and germ cells is likely to be critical for normal development of the testis. We have established and characterized cocultures of neonatal Sertoli cells and gonocytes and have begun to study the physical and functional relationship between these cells in vitro. Cells were isolated from rat pups by sequential enzymatic treatment and cultured in serum free medium. When plated on Matrigel, Sertoli cells rapidly attach, and gonocytes adhere to the underlying Sertoli cells shortly thereafter. We observed that some of these germ cells develop cytoplasmic processes and elongate during the first day of culture, essentially mimicking their behavior in vivo. Electron microscopic examination of typical cultures revealed the presence of desmosome like adhesion sites and apparent gap junctions between Sertoli cells and gonocytes. To determine whether Sertoli cells and gonocytes are functionally coupled in the cocultures, we used the glass bead-loading technique of McNeil and Warder to introduce Lucifer yellow (LY), a gap junction-permeant probe, and Rhodamine-dextran (RD), a larger marker excluded by gap junctions, simultaneously into cultures 24 h after plating. Immediate fixation and viewing of cultures with fluorescence microscopy indicated that all bead-loaded cells received both probes. We studied other living cultures 10 min after bead-loading and located RD negative (i.e. nonbead-loaded) gonocytes that were in obvious contact with RD- and LY-positive bead-loaded Sertoli cells; these gonocytes were scored for the presence or absence of cytoplasmic LY. This analysis revealed that many gonocytes were able to obtain LY from adjacent Sertoli cells, presumably via gap junctions maintained with these cells. In addition, we quantified the percentage of gonocytes that elongated with increasing time in vitro and correlated the morphology of these cells with their ability to acquire LY from adjacent Sertoli cells. Our findings indicate that although the absolute numbers of gonocytes present decreases, more of those remaining elongate as time in vitro increases. We can also conclude from our data that gonocytes with and without processes are equally likely to be coupled with Sertoli cells under these conditions. These observations provide the first demonstration of functional coupling between Sertoli cells and premeiotic germ cells. Together with our morphological observations, they suggest that gap junction-mediated communication between these cells may be involved in stimulating or regulating changes in the gonocyte population during postnatal development of the testis. PMID- 2249631 TI - 17 beta-estradiol stimulates the calbindin-D9k (CaBP9k) gene expression at the transcriptional and posttranscriptional levels in the rat uterus. AB - The 9 kilodalton vitamin D-dependent calcium-binding protein (CaBP9k), calbindin D9k, is expressed in the intestine and uterus of mammals. Rat intestinal CaBP9k is a well documented expression of the steroid hormone like action of 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3). In contrast exogenous 1,25-(OH)2D3 does not affect the concentration of uterine CaBP9k which is dependent on estrogen. We have analyzed the effect of 17 beta-estradiol on the regulation of CaBP9k gene expression in the uterus of mature ovariectomized rats. CaBP9k mRNA is undetectable in the uterus of mature ovariectomized rats. A single dose of 17 beta-estradiol results in a detectable level of CaBP9k mRNA at 1 h and a significant increase 3 h after injection. The maximal CaBP9k mRNA level is reached 6 to 12 h post injection. These results show that 17 beta-estradiol increases CaBP9k production by increasing CaBP9k gene transcription. Chronic 17 beta-estradiol administration results in a plateau of CaBP9k mRNA but in a large increase in CaBP9k concentration. The kinetic response to a single estradiol injection was similar in immature rats. This result shows that no cellular differentiation is required for the control of CaBP9k gene expression by 17 beta estradiol. The uterine cells of immature rats are already competent to respond optimally to estradiol. There is a single 0.5 kilobase CaBP9k gene transcript in the rat duodenum. In contrast there are two estrogen-inducible CaBP9k mRNA species in the uterus of both the mature ovariectomized and the immature rats. The smallest species corresponds to the duodenal CaBP9k mRNA species, while the larger species is at least 50 nucleotides larger. However, a unique CaBP9k identical to that in the duodenum is expressed in the uterus. PMID- 2249632 TI - Differentiation dependent biphasic regulation of adipsin gene expression by insulin and insulin-like growth factor-1 in 3T3-F442A adipocytes. AB - Adipsin is a serine protease with complement factor D activity that is synthesized by adipocytes and secreted into the blood stream. Expression of adipsin is deficient in models of genetic (ob/ob, db/db) and acquired (monosodium glutamate-lesioned) obesity, but the cellular mechanisms responsible for this deficiency are unknown. Because hyperinsulinemia is frequently associated with obesity, we evaluated the effects of this hormone and insulin-like growth factor 1 (IGF-1) on adipsin secretion and adipsin messenger RNA (mRNA) levels in 3T3 F442A adipocytes. In the present study, we report that in fully differentiated adipocytes (after 11 days post confluence), insulin exposure progressively decreases adipsin secretion by 40%, 67%, and 78% after 2, 4, and 6 days of treatment. The inhibition of adipsin secretion by insulin is the result of a corresponding decrease in adipsin mRNA and is specific since two other differentiation-dependent fat cell mRNAs encoding aP2 (a fatty acid binding protein) and glycerophosphate dehydrogenase (GPD), are unaffected. Insulin suppresses adipsin gene expression via high affinity insulin receptors, because physiological levels of insulin produce this effect, and dose-response curves for insulin stimulation of 2-deoxyglucose uptake and glucose utilization are similar to insulin's effect on adipsin. In contrast, insulin when present during days 1-8 post confluence (during differentiation) markedly increases adipsin secretion and adipsin mRNA levels. This stimulation is due to the ability of insulin to accelerate differentiation as evidenced by corresponding increases in aP2 and GPD mRNAs as well. Insulin and IGF-1 are equipotent in this effect, suggesting that both insulin and IGF-1 receptors can mediate this response. In summary, during the differentiation of 3T3-F442A adipocytes, insulin stimulates adipsin gene expression by accelerating differentiation. As the cells become mature adipocytes, they acquire some differentiation-dependent factor, which couples insulin receptor stimulation to inhibition of adipsin gene expression. This model should aid our search for the molecular links between insulin receptor stimulation and altered gene expression. PMID- 2249633 TI - Hormonal regulation of thecal cell function during antral follicle development in bovine ovaries. AB - The hormonal regulation of thecal cell function was investigated with cells isolated at various stages of antral follicle development. Bovine thecal cells were isolated from small antral, medium antral, and large Graffian follicles (small, medium, and large ovarian follicles). Serum-free cultures of thecal cells were established and viable for a minimum of 6-8 days of culture. The purity of the thecal cell population was characterized cytochemically and was found to contain less than 5% endothelial cell and/or granulosa cell contamination. The steroidogenic capacity of this purified population of thecal cells in serum-free culture was examined through an analysis of androgen and progesterone production. Androgen production was high during the first 3 days of culture, then declined to undetectable levels. Production of androstenedione was approximately 10-fold higher than production of testosterone. Progesterone production remained relatively constant throughout the 8-day culture period. hCG was found to stimulate androgen production during days 1-3 of culture, but had a negligible effect on progesterone production. In contrast, hCG stimulated progesterone production during days 3-6 of culture, but had a negligible effect on androgen production. Insulin stimulated progesterone production during days 3-6 of culture, but had no effect on androgen or progesterone production during days 1-3 of culture. The minimum effective concentrations of hCG and insulin required to stimulate steroidogenesis of the thecal cells ranged from approximately 1-10 ng/ml. Addition of serum to the cultures decreased androgen production and suppressed the hormone responsiveness of the cells. Thecal cells in culture appear to alter their steroidogenic capacity from an androgen-producing cell to a progesterone-producing cell. Analysis of the developmental regulation of thecal cell function revealed that androgen production and hormone responsiveness were relatively constant in small, medium, and large follicles. In contrast, progesterone production and hormone responsiveness were highest in small follicles, intermediate in medium follicles, and lowest in large follicles. A more general analysis of the developmental regulation of thecal cell function examined the secretion of radiolabeled proteins. A large number of radiolabeled proteins were secreted by thecal cells, ranging in molecular mass from 5-500 kDa. Interestingly, insulin and hCG had no major effect on secretion of proteins by cells isolated from any of the stages of development examined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249634 TI - Estrogen regulation of thecal cell steroidogenesis and differentiation: thecal cell-granulosa cell interactions. AB - Estrogen regulation of thecal cell steroidogenesis and differentiation was investigated with cells from ovarian antral follicles. Bovine theca interna cells were isolated and cultured in serum-free conditions to evaluate the effects of estradiol on thecal cell production of androstenedione, testosterone, and progesterone. Estradiol increased thecal cell androgen production throughout a 6 day culture period; however, the basal and stimulated levels of androgen production diminished after day 3 of culture. Androstenedione accumulation was approximately 10-fold greater than that of testosterone. In contrast to the stimulatory effects that estradiol had on androgen production, estradiol suppressed progesterone production throughout the 6-day culture period. Comparison of the effects of estradiol and hCG on thecal cells from small (less than 5 mm), medium (5-10 mm), and large (greater than 10 mm) antral follicles demonstrated that estradiol stimulated androgen production to a greater extent than hCG with cells from all of these stages of follicle development. Estradiol stimulation of androstenedione was greater in theca from small follicles than in theca from medium or large follicles. In contrast, suppressive effects of estradiol on progesterone were most apparent on thecal cells from medium and large follicles and less apparent on theca from small follicles. Estradiol stimulated androstenedione production in a dose-dependent fashion, with a minimum effective concentration of 10(-9) M and a maximum effective concentration of 10( 7)-10(-6) M. Concentrations greater than 10(-6) M estradiol resulted in a decline in the stimulatory response and may be important in the preovulatory follicle to suppress thecal cell androgen production and initiate the process of luteinization. Progesterone production was slightly stimulated by 10(-9) M estradiol, whereas higher concentrations (10(-7)-5 x 10(-6) M) resulted in a dose dependent suppression of progesterone production. Interestingly, combined treatment of thecal cells with estradiol and hCG resulted in a greater than additive stimulation of androstenedione production, and estradiol decreased the ability of hCG to stimulate progesterone production. Observations demonstrate that estradiol can dramatically alter thecal cell production of steroids and support a hypothesis that steroid-mediated interactions between granulosa and thecal cells play an important role in regulating cellular function within follicles. The data provide evidence that a local feedback loop may exist in ovarian follicles, where androgens produced by thecal cells are used as a substrate for granulosa cell aromatization into estrogens, which, in turn, may feed back to stimulate thecal cell production of androgens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249635 TI - Luteinizing hormone causes rapid and transient changes in rat Leydig cell peroxisome volume and intraperoxisomal sterol carrier protein-2 content. AB - The aim of the present study was to investigate the effects of a single injection of LH on rat Leydig cell peroxisome volume and peroxisomal sterol carrier protein 2 (SCP2) content. Sexually mature Sprague-Dawley rats (n = 5) were injected sc with 500 micrograms LH and euthanized, and trunk blood was collected at 0, 0.5, 1, 2, and 3 h. Additionally, LH-treated rats were whole body perfused-fixed, and their testes were processed for qualitative and quantitative histochemical and immunocytochemical studies at 0, 0.5, 1, and 2 h. Peroxisomes were identified by cytochemical staining for catalase activity with the alkaline 3,3' diaminobenzidine tetrahydrochloride method. Catalase and SCP2 were immunolocalized in Leydig cell organelles via 10-nm AuroProbe EM protein-A gold particles. Peak plasma testosterone concentrations were observed 1 and 2 h after the single sc LH injection. The average volume of a Leydig cell was unchanged by the LH treatment at all time points tested. Similarly, the absolute volumes of smooth endoplasmic reticulum and mitochondria per Leydig cell were unchanged at all time points tested. By contrast, the absolute volume of peroxisomes per Leydig cell increased 3-fold 0.5 h after LH injection (P less than 0.01) and then returned to control values by 2 h. The absolute volume of negative bodies (single membrane-bound cytoplasmic organelles lacking catalase) per Leydig cell was elevated above the control value 0.5 and 1 h after LH injection. Western blot analysis demonstrated a single protein at 14 and 60 kDa with anti-SCP2 and anticatalase, respectively, for both homogenates obtained from liver and purified Leydig cells. Quantitative immunocytochemical studies demonstrated that the gold particle density representing SCP2 over peroxisomes increased 5-fold 0.5 h after the LH injection (P less than 0.01) and then returned to control values by 2 h. In contrast, the gold particle density representing catalase over peroxisomes was not different in control and LH-injected groups. We conclude that a single sc injection of LH causes a rapid, specific, and transient increase in both the volume of peroxisomes and the peroxisomal content of SCP2 in Leydig cells. PMID- 2249636 TI - Effect of transforming growth factor-beta 1 on proliferation and death of rat prostatic cells. AB - The ability of transforming growth factor B1 (TGF beta 1) to inhibit proliferation and activate death of rat ventral prostatic glandular cells was tested both in vivo and in vitro. In vivo administration of 50 ng TGF beta 1/day directly to the regressed ventral prostate of previously castrated male rats had no effect on the proliferative regrowth of the prostatic glandular cells induced by exogeneous androgen replacement. In addition, androgen-stimulated ventral prostatic cell proliferation in vitro in organ culture was not affected by exposure to 0.1-20 ng/ml TGF beta 1. In contrast in vivo administration of 50 ng TGF beta 1/day directly to the ventral prostate of intact noncastrated male rats resulted in the death of about 25% of the prostatic glandular cells within 7 days of treatment. Such TGF beta 1 treatment did not lower serum testosterone, nor did it affect the size or DNA content of the seminal vesicles, demonstrating the local nature of the response. Likewise, in androgen-maintained ventral prostate organ cultures in vitro, there was a dose-response relationship between glandular cell death and TGF beta 1 concentration in the medium. These results demonstrate that TGF beta 1 can induce the death of androgen-dependent prostatic glandular cells even when physiological levels of androgen are present. Previous studies have demonstrated that both the receptor and the mRNA for TGF beta 1 increase rapidly in the ventral prostate after castration. Taken with the present data, these results suggest that TGF beta 1 may be a physiological intermediate in the programmed cell death of rat prostatic glandular cells activated after androgen ablation. PMID- 2249638 TI - Mechanisms underlying the acceleration of thyroid hormone-induced tadpole metamorphosis by corticosterone. AB - Adrenal steroids have been shown to accelerate both spontaneous and thyroid hormone (TH)-induced metamorphosis. The present study is concerned with the mechanisms underlying this effect. Premetamorphic Rana catesbeiana tadpoles were immersed in water containing 1-20 nM T4 or T3 +/- 1 microM corticosterone (B) for 6 to 19 days. B is the predominant glucocorticoid in tadpole plasma before climax. As indicated by the rate of tail resorption and hepatic carbamyl phosphate synthetase (CPS) activity, metamorphosis was significantly accelerated when TH-treated animals also received B: after 14 days in T4 (20 nM), tadpole tail length was decreased by 10%; in T4 + B, the decrease was 19%. At the same time, CPS activity was increased approximately 12-fold in tadpoles in T4 and 18 fold in those in T4 + B. Comparable results were obtained when T3 was employed. Neither tail resorption nor CPS activity was influenced by B alone. Plasma T4 levels attained at all bath concentrations of T4 were increased more than 2-fold when B was present. The same was true when T3 was used. In addition, in tadpoles immersed in 20 nM T4, the plasma T3 level-was significantly increased in the presence of B. Assessment of 5'-deiodinase and 5-deiodinase activities in vitro revealed that administration of B for 7 days resulted in a significant increase in 5'-deiodinase activity in skin and a significant reduction in T3 5-deiodinase activity in both liver and gut. Treatment with B reduced the rate of turnover of T3; 72 h after injection of 0.01 nmol [125I]T3, B-treated tadpoles had retained approximately 58% of the dose vs. 42% in controls. T3 nuclear receptor number (sites per nucleus) as assessed by an in vitro saturation technique was not altered in liver, tail, or red blood cells after 14 days of exposure to B. On the basis of these findings it is suggested that the acceleration of TH-induced metamorphosis by B is due at least in part to its ability to increase the plasma level of T4 or T3 through its effects on the peripheral metabolism of TH. HD 09020 PMID- 2249637 TI - Expression of the oxytocin and vasopressin genes in human and baboon gonadal tissues. AB - A variety of molecular techniques were used to search human and baboon gonadal tissues for evidence of transcription of the genes for the peptide hormones oxytocin and vasopressin. Only a highly sensitive assay based on a modification of the polymerase chain reaction succeeded in detecting mRNA copies of the oxytocin gene in both human and baboon corpus luteum. Vasopressin gene transcription was not detected in human testis and corpus luteum and was found only once in four different experiments in baboon corpus luteum. Evidence for oxytocin gene transcription in the human testis was found in three of five experiments. The method employed and subsequent sequence analysis of the polymerase products verified the presence of oxytocin mRNA with normal hypothalamic-type exonic structure in primate corpus luteum. Nevertheless, the very low levels of mRNA present are unlikely to support other than local functions for the encoded nonapeptide hormones. PMID- 2249639 TI - Characterization of 11 beta-hydroxysteroid dehydrogenase gene expression: identification of multiple unique forms of messenger ribonucleic acid in the rat kidney. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) appears to be involved in mediating aldosterone specificity of otherwise nonselective type I receptors in mineralocorticoid target tissues. In the present study gene expression of 11 HSD was characterized in various tissues of the rat by use of a complementary DNA probe coding for the rat liver 11-HSD. In the liver, lung, testis, colon, heart, hippocampus, and kidney papilla a single message was observed of length approximately 1700 nucleotides (nt). In the kidney cortex/medulla, however, messenger RNA (mRNA) species were observed at 1900 nt, 1600 nt and 1500 nt, and deadenylation studies showed that the renal 1900 nt species was heterogeneous. Northern blot analysis of 11-HSD mRNA showed low levels of expression in the kidney of the neonate and much higher levels in liver and lung with expression increasing markedly in all three tissues over development. In mature rats, a low salt diet significantly elevated 11-HSD mRNA in the liver but not in other tissues. We interpret these data as evidence for the existence of a family of 11 HSD genes, and consistent with the possibility that the hepatic species may modulate occupancy of type II (classical) glucocorticoid rather than type I receptors. PMID- 2249640 TI - Effects of electrical stimulation of the medial basal hypothalamus on the in vivo release of luteinizing hormone-releasing hormone in the prepubertal and peripubertal female monkey. AB - In this study the hypothesis that the LHRH neurosecretory system of the prepubertal female monkey has the capacity to function in a manner comparable to that of monkeys in more mature stages of development was tested. Using push-pull perfusion in the stalk-median eminence, effects of electrical stimulation of the medial basal hypothalamus on in vivo LHRH release were determined in conscious prepubertal, early pubertal, and midpubertal monkeys. After a 180-min period of baseline sample collection, electrical stimulation was applied six times at 90 min intervals via a monopolar electrode, the tip of which was 1-2 mm rostro dorsal to the perfusion site. Control experiments were performed in the same manner, but without electrical stimulation. During control perfusions, the mean LHRH level remained stable. Mean (+/- SEM) LHRH release for the entire perfusion period in control experiments was 0.5 +/- 0.2, 2.4 +/- 0.4, and 2.2 +/- 0.7 pg/ml.10 min for the prepubertal (n = 6), early pubertal (n = 4), and midpubertal (n = 6) groups, respectively. Mean LHRH release in the prepubertal group was significantly lower than that in either of the older groups (P less than 0.05). In contrast, in all three age groups, repeated electrical stimulation of the medial basal hypothalamus resulted in 1) a short latency increase in LHRH release occurring within 20 min after each stimulation, and/or 2) a gradual increase in mean LHRH release over several hours. In the prepubertal group (n = 4), mean LHRH levels were 0.8 +/- 0.5 pg/ml.10 min during the 90 min before the first electrical stimulation and increased to 6.1 +/- 2.9 pg/ml.10 min during the 90 min after the sixth stimulation. This degree of responsiveness was similar to that of the older age groups. Mean LHRH levels before stimulation were 1.3 +/- 0.6 and 2.4 +/- 1.1 pg/ml.10 min in the early pubertal (n = 5) and midpubertal (n = 5) groups, respectively, and increased to 7.8 +/- 3.5 and 6.0 +/- 1.8 pg/ml.10 min, respectively, after the sixth stimulation. These increases in LHRH concentration with electrical stimulation were significant for all three age groups (P less than 0.03-0.001), while there were no significant differences between age groups. The temporal patterns of these responses suggest that electrical stimulation elicits LHRH release with a similar magnitude in all three age groups by 1) depolarizing LHRH neurons directly, and/or 2) stimulating multineuronal systems that synapse with LHRH neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249641 TI - Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: I. Alterations in cytosolic-free calcium levels and calcium flux. AB - The effect of prostaglandin F2 alpha (PGF2 alpha) on cytosolic calcium homeostasis was studied in suspensions of ovine large or small luteal cells from superovulated ewes. In large cells loaded with fura-2 (AM), resting cytosolic free calcium ([Ca2+]i) was 62 +/- 5 nM (Hanks' medium, pH 7.15), and PGF2 alpha (0.5 microM) induced a rapid transient increase in [Ca2+]i to 152 +/- 6 nM, which then decreased to 97 +/- 6 nM within 3 min and remained at this level for the remainder of the treatment period (10-20 min). PGF2 alpha did not alter intracellular pH (pHi) in cells loaded with snarf-1 (AM) (pHi indicator). The transient nature of the [Ca2+]i increase was due, at least in part, to the ability of PGF2 alpha to stimulate (P less than 0.05) 45Ca2+ efflux. In small cells, resting [Ca2+]i was 57 +/- 5 nM, and no change in [Ca2+]i levels or pHi occurred with the addition of PGF2 alpha. PGF2 alpha also did not affect 45Ca2+ efflux in small cells. Calcium uptake was not significantly altered by PGF2 alpha in large or small cells. Data from kinetic analysis of the calcium transient was best fit to a two-compartment model consisting of a rapidly effluxing compartment and a slowly effluxing compartment. The size and rate constants were 62 +/- 10 nM and 3.6 +/- 1 min-1, respectively, for the rapidly effluxing compartment and 140 +/- 9 nM and 0.02 +/- 0.002 min-1, respectively, for the slowly effluxing compartment. These results provide evidence for a direct effect of PGF2 alpha specifically on the ovine large luteal cell that involves alterations in [Ca2+]i and calcium flux. This effect is likely to be involved in intracellular mediation of the signal for luteal regression. PMID- 2249642 TI - Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism. AB - We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of [3H]F/[14C]E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E (%F----E = 17 +/- 4; %E----F = 27 +/- 7) to preferential oxidation of F (%F----E = 26 +/- 2; %E----F = 5 +/- 2), a pattern similar to that at term (%F----E = 32 +/- 6; %E----F = 9 +/- 4). In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production. These findings provide indirect evidence that supports our hypothesis that the change in placental F-E metabolism induced by increasing estrogen late in pregnancy results in activation of the fetal hypothalamic-pituitary adrenocortical axis and, thus, ontogenesis of fetal F production near term. PMID- 2249643 TI - Transplantable rat choriocarcinoma cells express placental lactogen: identification of placental lactogen-I immunoreactive protein and messenger ribonucleic acid. AB - The purpose of this investigation was to evaluate the abilities of a transplantable rat choriocarcinoma (Rcho) to produce placental PRLs. The Rcho tumor was analyzed biochemically and histologically for the expression of placental PRLs. Expression of placental PRL mRNAs was determined by Northern blot and in situ hybridization analyses. Expression of placental PRL proteins was determined by Western blot and immunocytochemical analyses. Histologically, Rcho tumors were characterized by the appearance of giant cell surrounding hemorrhagic regions. Female rats bearing the Rcho tumor beneath their kidney capsule showed extensive mammary gland development. The Rcho tumors expressed placental lactogen I (PL-I) mRNA and protein, but there was no evidence of placental lactogen-II (PL II), PRL-like protein-A (PLP-A), or PRL-like protein-B (PLP-B). Rcho PL-I mRNA and proteins migrated as a 1-kilobase species and a 36- to 40-kDa species similar to those expressed by normal rat trophoblast tissues. The cell type responsible for Rcho PL-I production was the giant cell, similar to that observed in normal rat trophoblast tissues. In summary, we have demonstrated the production of PL-I by a transplantable rat choriocarcinoma (Rcho). The Rcho tumor resembles rat trophoblast tissue at early postimplantation stages (days 6-10 of gestation) and may be a useful tool for studying placental PRL expression during trophoblast differentiation. PMID- 2249644 TI - Generation and characterization of monoclonal antibodies directed against noniodinated and iodinated thyroglobulin, among which are antibodies against hormonogenic sites. AB - In this paper we describe the preparation and characterization of three different groups of monoclonal antibodies (Mabs) raised against iodinated and noniodinated human thyroglobulin (hTg). One group (A) of three Mabs is directed against hTg without discrimination between different iodine contents of Tg. The second group (B) of three Mabs has a higher affinity for iodinated Tg than for noniodinated Tg, and the Mabs are not species specific. The last group (C) of two Mabs generated against noniodinated hTg shows a higher affinity for noniodinated hTg than for iodinated hTg. From competition experiments with T4 we conclude that the second group of Mabs is directed against hormonogenic sites in the protein. From these Mabs, probably two are directed against the N-terminal hormonogenic site, and one against one of the C-terminal hormonogenic sites in Tg. Reactivity of the Mabs of group B with Tgs of various degrees of iodination indicates that the N terminal T4 is formed first. PMID- 2249645 TI - In vivo and in vitro effects of a cyclopropenoid fatty acid on ovine corpus luteum function. AB - Experiments were conducted to examine the effect of a cyclopropenoid fatty acid (CPFA) on progesterone (P4) production by the ovine corpus luteum (CL) during the estrous cycle. Ewes in Exp 1 and 2 were laparotomized on day 2 of the estrous cycle, and animals with CL in both ovaries were subjected to unilateral ovariectomy. Ewes with CL in one ovary only were not ovariectomized. During surgery, ewes were injected with a mixture of fatty acids (sterculic acid, 39%; palmitic, 29%; linoleic, 12%; malvalic acid, 9%; oleic, 8%; stearic, 3%) containing 500 micrograms sterculic acid (SA; Exp 1), 750 micrograms SA, or 750 micrograms oleic acid (Exp 2) via the artery supplying the ovary bearing the CL. Control ewes were similarly injected with vehicle only (0.1-0.2 ml dimethylsulfoxide; Exp 1 and 2, respectively). Sera from blood samples collected at 15-min intervals for 1 h after injection or once daily on alternate days of the cycle after surgery were analyzed for LH and P4, respectively. In Exp 3, slices of CL removed from five ewes on day 10 of the cycle were incubated for 90 min in medium containing 100 ng/ml SA or vehicle (10 microliters dimethylsulfoxide). Slices were then reincubated for 90 min in medium containing 10 ng/ml oLH or saline (10 microliters). Tissue and medium were analyzed for P4. Injection of 500 micrograms SA suppressed serum levels of P4 (P less than 0.01), but did not alter mean cycle length. Injection of 750 micrograms SA reduced serum concentrations of P4 and shortened estrous cycle duration (P less than 0.005). Oleic acid (750 micrograms) or as much as 1.9 mg of a mixture of fatty acids devoid of CPFA had no effect on cycle length or serum levels of P4, suggesting that altered luteal function was due to the type and not the quantity of fatty acid injected. Treatments had no effect on serum concentrations of LH. Preincubation with SA interfered with the ability of luteal slices to synthesize P4 when subsequently incubated alone or with ovine LH (P less than 0.01). It is concluded that SA acts on the CL to impair steroidogenesis and ultimately cause luteal regression. PMID- 2249646 TI - Activin stimulates spermatogonial proliferation in germ-Sertoli cell cocultures from immature rat testis. AB - Activin and inhibin are peptide hormones produced in the gonads which may act as autocrine and/or paracrine regulators of testicular function. Sertoli cells produce inhibin, and it has recently been shown that Leydig cells can produce activin in vitro. To further explore the local actions of activin and inhibin in the testis, Sertoli and germ cells were isolated from immature rats and cocultured in vitro. In these cultures we demonstrate that activin A and activin B, but not inhibin A, stimulated spermatogonial proliferation in vitro. Activin increased [3H]thymidine incorporation 2- to 4-fold in cocultures after 48-72 h of treatment. Using autoradiography, the label was localized in the clusters of spermatogonia adhering to the Sertoli cell monolayer. Additionally, activin stimulated a reaggregation of the cultures into tubule-like structures. Fluorescence-activated cytometry was used to analyze the cell population based on size, DNA content, and lipid content. Sertoli cells were identified using Nile Red staining of intracellular lipid droplets; spermatogonia are Nile Red negative. Activin treatment caused a marked increase in the fraction of Nile Red negative cells in the cocultures. Activin also caused an increase in the percentage of these cells having 4C DNA. Lastly, specific binding of activin A to 2C, but not 4C, germ cells was demonstrated. These data demonstrate that activin acts as a regulator of spermatogonial proliferation in the male. PMID- 2249647 TI - Postnatal growth of mouse seminal vesicle is dependent on 5 alpha dihydrotestosterone. AB - The seminal vesicles (SV) develop from the lower portion of the Wolffian ducts (WD) in response to androgens, which prevent their degeneration and subsequently stimulate organogenesis of the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. Earlier studies suggest that testosterone (T) is the active androgen for WD development. By contrast, development of urogenital sinus and external genitalia is dependent upon 5 alpha-dihydrotestosterone (DHT), produced by 5 alpha-reductase within the target tissue itself. To reevaluate the possible role of DHT during SV morphogenesis, SVs from 0-day-old (day of birth) mice were grown for 3, 6, or 9 days in either serum-free or serum-containing medium in the presence or absence of T (10(-7) M) or DHT (10(-8) M). The serum-free medium consisted of Ham's F-12-Dulbecco's Modified Eagle's Medium (1:1) containing insulin, transferrin, cholera toxin, BSA, and epidermal growth factor. The serum containing medium was Ham's F-12-Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum. Epithelial branching morphogenesis of SVs occurred in serum free or serum-containing medium supplemented with either T or DHT and was comparable to that of SVs of similar ages in vivo. In serum-containing medium the DNA content of the cultures was about 2-fold higher in T-containing vs. T deficient medium. However, in serum-free medium the DNA content was the same in cultures grown with or without T. SVs cultured under serum-free conditions in the presence of T plus 390 MSD (17 beta-N,N-diisopropylcarbamoyl-4-aza-5 alpha androstan-3-one, an inhibitor of 5 alpha-reductase) were completely inhibited in their development, while in the presence of DHT plus 390 MSD, branching morphogenesis was comparable to that in SVs cultured in the presence of T or DHT alone. In medium lacking either T or DHT, SV development was inhibited. In addition, it was confirmed by TLC that [1 beta,2 beta-3H]T was converted into [3H]DHT at the ratio of 15.4% for the first 2 days and at 35.3% for the subsequent 2 days of the culture of SVs in serum-free medium. These data demonstrate that T is important as a precursor of DHT and DHT is the major androgen in the postnatal development of mouse SVs from the lower WD. PMID- 2249648 TI - Localization of insulin receptor mRNA in rat brain by in situ hybridization. AB - Insulin receptor mRNA was demonstrated in rat brain slices by in situ hybridization with three 35S-oligonucleotide probes and contact film autoradiography. Specificity was confirmed by showing that (a) excess unlabeled probe abolished the signal, (b) an oligonucleotide probe for rat neuropeptide Y mRNA showed a different distribution of hybridization signal, and (c) the distribution of insulin receptor binding was consistent with the distribution of insulin receptor mRNA. Insulin receptor mRNA was most abundant in the granule cell layers of the olfactory bulb, cerebellum and dentate gyrus, in the pyramidal cell body layers of the pyriform cortex and hippocampus, in the choroid plexus and in the arcuate nucleus of the hypothalamus. PMID- 2249649 TI - Structure and sexual dimorphic expression of a liver-specific rat 3 beta hydroxysteroid dehydrogenase/isomerase. AB - The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) catalyzes the obligatory oxidation and isomerization of delta 5-3 beta hydroxysteroid precursors into delta 4-3-ketosteroids which lead to the formation of all classes of steroid hormones. We report the molecular cloning of a third type of cDNA clone encoding rat 3 beta- HSD isolated from a rat liver lambda gt11 cDNA library. The nucleotide sequence of 1955 bp determined from overlapping cDNA clones predicts a protein of 372 amino acids which displays 80% similarity with that of rat type I and type II 3 beta-HSD proteins. RNA blot analysis reveals the presence of mRNA transcripts of 2.1 kb in male liver in contrast to the 1.7 kb mRNA species detected in adrenal and gonad poly(A)+ RNA. Ribonuclease protection assays using type I, type II and type III specific cRNA probes demonstrate the liver-specific expression of type III mRNA while the two others are expressed in adrenals and gonads. The type III mRNA species was below the detection limit in intact female liver while in hypophysectomized females, its accumulation was restored to 55% of the levels measured in intact or hypophysectomized male rats. The present data describe the presence of a third type of 3 beta-HSD mRNA species and its marked sexual dimorphic gene expression in the liver which apparently results from pituitary hormone-induced gene repression in female rat liver tissue. PMID- 2249650 TI - Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance. AB - To mimick a state of hyperinsulinemia, normal rats were infused with insulin for 4 days via minipumps, and compared to saline infused rats. At the end of the experimental period, the abundance of mRNA was increased in white adipose tissue (WAT) and decreased in muscles of "insulinized" rats compared to controls. These findings were accompanied, in all tissues considered, except the diaphragm, by parallel changes in the amount of the glucose transporter protein and by parallel changes in the in vivo glucose utilization index. Hyperinsulinemia is thus a driving force in stimulating adipose tissue metabolic activity, while bringing about incipient muscle insulin resistance. PMID- 2249651 TI - Inhibition of lymphocyte mediated cytotoxicity by perforin antisense oligonucleotides. AB - The granule/perforin exocytosis model of CTL mediated cytolysis proposes that CTL, upon recognition of the specific targets, release the cytolytic, pore forming protein perforin into the intercellular space which then mediates the cytotoxic effect. However, direct evidence for the involvement of perforin is still lacking, and indeed, recent results even seem incompatible with the model. To determine directly the role of perforin in CTL cytotoxicity, perforin antisense oligonucleotides were exogenously added during the stimulation of mouse spleen derived T cells and human peripheral blood lymphocytes (PBL), respectively. Perforin protein expression in lymphocytes was reduced by up to 65%, and cytotoxicity of stimulated T cells by as much as 69% (5.7-fold). These results provide the first experimental evidence for a crucial role of perforin in lymphocyte mediated cytotoxicity. PMID- 2249652 TI - Activated T cells transcribe an alternatively spliced mRNA encoding a soluble form of Qa-2 antigen. AB - Among the best characterized non-classical mouse major histocompatibility antigens are the Qa-2 molecules. These proteins can serve as targets for allogenic cytotoxic T cells and as signal transducing molecules. They are structurally similar to H-2 transplantation antigens in their N-terminal and beta 2-microglobulin binding domains but differ at their C-termini. While the H-2 antigens span the cell membrane, the Qa-2 molecules are attached to the cell surface via phospholipid anchors. The genetic information encoding this attachment is contained in exon 5. In concanavalin A activated splenocytes the expression of membrane bound Qa-2 antigens declines and, simultaneously, soluble forms of Qa-2 molecules are secreted. We demonstrate here that the soluble Qa-2 polypeptides are translated from alternatively spliced mRNAs lacking exon 5, while the membrane forms are encoded by the full-size transcripts. In cultured cells the alternative splicing of the Qa-2 message is induced by T-cell activation splicing of the Qa-2 message is induced by T-cell activation with concanavalin A. The canonical mRNA encoding the membrane form of Qa-2 predominates in unstimulated mouse tissues but the cultured cell lines, like activated T cells, express enhanced levels of the truncated mRNA. In some cell lines almost all Qa-2 transcripts lack exon 5. For example, in L cells, mRNAs encoding soluble Qa-2 molecules are at least 10 times more abundant than Qa-2 transcripts encoding phospholipid anchored antigens. These findings are discussed in terms of potential functions of membrane bound and secreted Qa-2 molecules. PMID- 2249653 TI - Fatty acids on the A/Japan/305/57 influenza virus hemagglutinin have a role in membrane fusion. AB - The covalent attachment of fatty acid moieties to proteins is a widespread post translational modification of viral and cell proteins yet the functional consequences of acylation are not well understood. We have determined that the A/Japan/305/57 influenza virus hemagglutinin (HA) contains three potential acylation sites at cysteine residues 211, 218 and 221 in the cytoplasmic domain of the molecule. Site-directed mutagenesis of one or more of these sites has no effect on biosynthesis, transport or receptor binding activity of the molecule; however, modification of any single site is sufficient to abolish completely or inhibit severely membrane fusion activity, a function essential for virus infectivity. We present a molecular model of the transmembrane and cytoplasmic domains of the HA to illustrate the potential orientation of these fatty acids and to provide a conceptual framework for further experimentation. PMID- 2249656 TI - Partial agonist/antagonist mouse interleukin-2 proteins indicate that a third component of the receptor complex functions in signal transduction. AB - Some mouse interleukin-2 (mIL-2) proteins with substitutions at residue Gln141 are unable to trigger a maximal biological response. The Asp141 protein induces the lowest maximal response. The Asp141 protein can weakly antagonize the biological activity of mIL-2 and strongly antagonizes the biological activity of active mIL-2 mutant proteins that have defects in interactions with the high affinity receptor. Residue 141 mutant proteins bind with reduced affinity to T cells expressing the high affinity IL-2 receptor, yet bind normally to transfected fibroblasts expressing only the alpha and beta chains of the receptor. These results suggest that a third receptor component is important for both binding and signal transduction. PMID- 2249655 TI - Anionic subsites of the acetylcholinesterase from Torpedo californica: affinity labelling with the cationic reagent N,N-dimethyl-2-phenyl-aziridinium. AB - Several peptides of acetylcholinesterase of Torpedo californica labelled with the alkylating reagent [3H]N,N-dimethyl-2-phenyl-aziridinium (DPA) were localized within the primary structure. One peptide had the sequence KPQELIDVE (positions 270-278); the incorporation of DPA into this peptide could be specifically suppressed by propidium, which suggests that it is part of the peripheral anionic site. The incorporation of DPA into two other peptides was insensitive to propidium but could be prevented by edrophonium; the sequence of one of the peptides assumed to be part of the anionic site in the catalytic centre was found to be DLFR (positions 217-220). Decamethonium efficiently blocked alkylation by DPA in all three investigated peptides. PMID- 2249654 TI - Genetic analysis of an MDR-like export system: the secretion of colicin V. AB - The extracellular secretion of the antibacterial toxin colicin V is mediated via a signal sequence independent process which requires the products of two linked genes: cvaA and cvaB. The nucleotide sequence of cvaB reveals that its product is a member of a subfamily of proteins, involved in the export of diverse molecules, found in both eukaryotes and prokaryotes. This group of proteins, here referred to as the 'MDR-like' subfamily, is characterized by the presence of a hydrophobic region followed by a highly conserved ATP binding fold. By constructing fusions between the structural gene for colicin V, cvaC, and a gene for alkaline phosphatase, phoA, lacking its signal sequence, it was determined that 39 codons in the N-terminus of cvaC contained the structural information to allow CvaC-PhoA fusion proteins to be efficiently translocated across the plasma membrane of Escherichia coli in a CvaA/CvaB dependent fashion. This result is consistent with the location of point mutations in the cvaC gene which yielded export deficient colicin V. The presence of the export signal at the N-terminus of CvaC contrasts with the observed C-terminal location of the export signal for hemolysin, which also utilizes an MDR-like protein for its secretion. It was also found that the CvaA component of the colicin V export system shows amino acid sequence similarities with another component involved in hemolysin export, HlyD. The role of the second component in these systems and the possibility that other members of the MDR-like subfamily will also have corresponding second components are discussed. A third component used in both colicin V and hemolysin extracellular secretion is the E. coli host outer membrane protein, TolC. PMID- 2249657 TI - Negative autoregulation of c-myc gene expression is inactivated in transformed cells. AB - Negative feedback regulation of c-myc gene expression has been observed in some, but not all, cell types. In order to demonstrate conclusively the existence of this mechanism and gain insight into the cause of its inactivation, we have directly examined its function in B cells and then investigated its activity in a number of cell types. We demonstrate the existence of negative c-myc autoregulation by showing the rapid, dose dependent and reversible suppression of endogenous c-myc expression in EBV-immortalized B lymphoblastoid cells transfected with a c-myc gene expressed under the control of a heavy metal inducible promoter. Autoregulation occurs at the level of transcriptional initiation and is mediated by at least one stable intermediate or cofactor molecule. The c-myc autoregulatory mechanism was found operative in all (11 of 11) non-tumorigenic cells tested, including normal and immortalized lymphocytes and fibroblasts. However, this mechanism was found to be inactive in all (10 of 10) tumor cell lines derived from a variety of tissues including those carrying normal and oncogenically activated c-myc genes. These data establish the existence of an important regulatory circuit modulating c-myc expression in normal cells and suggest that its inactivation may represent a general regulatory disturbance of transformed cells. PMID- 2249659 TI - In vitro transcription and DNA binding characteristics of chloroplast and etioplast extracts from mustard (Sinapis alba) indicate differential usage of the psbA promoter. AB - The psbA gene which is differentially expressed in vivo in chloroplasts and etioplasts has an unusual promoter, containing both prokaryotic-type '-35' and ' 10' elements and a sequence motif that resembles the nuclear TATA box. Single base pair substitutions were introduced into the mustard psbA promoter and the mutants were tested in transcription and DNA binding experiments, using extracts from either chloroplasts or etioplasts. Positions within the '-35' region appear to play an essential role in the chloroplast but not in the etioplast system. Altering the first or second position of the 'TATA box'-like region led to decreased psbA in vitro transcription in either plastid extract. These two mutations, however, did not affect binding of extracts to the (linear) psbA promoter fragment in gel retardation assays. Fragments carrying two other plastid promoters effectively competed psbA promoter binding of the etioplast extract, but more weakly that of the chloroplast extract. Lambda exonuclease mapping shows that the 5' border of the binding region is more upstream with the etioplast than with the chloroplast system, whereas the 3' border appears to be the same. Hence, protein(s) of the two plastid types seem to interact differently with the mustard psbA promoter in vitro and perhaps also in vivo. PMID- 2249658 TI - Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor. AB - RU486 induced the binding to a palindromic progestin responsive element (PRE) in vitro of homo- and heterodimers of the human progesterone receptor (hPR) isoforms A and B, present in T47D breast cancer cells or in HeLa cells transiently expressing the recombinant proteins. The resulting complexes were indistinguishable from those induced with the agonist R5020 with respect to specificity, affinity and stability. Ligand exposure was a necessary prerequisite to observe PR/PRE complexes. Antagonist-induced complexes migrated more rapidly during electrophoresis than agonist-induced ones, and no 'mixed' PR/RU486 PR/R5020 complexes were observed, suggesting that the dimerization interfaces of agonist- and antagonist-bound molecules are non-compatible. The analysis of a series of deletion mutants and chimeric receptors revealed the presence of two transcription activation functions (TAFs), located in the N-terminal region A/B (TAF-1) and the hormone binding domain (TAF-2). In the presence of agonists, both TAFs were active in HeLa cells. In the presence of RU486 TAF-2 was inactive, while TAF-1 within the hPR form B/RU486 complex activated transcription from a reporter gene containing a single palindromic PRE. We consider this to be the most convincing evidence that the receptor/RU486-complex does in fact bind to PREs in vivo. No transcriptional activation was observed in the presence of RU486 from a reporter gene containing the complex MMTV-LTR PRE. In contrast to hPR form B, form A was not able to activate transcription from PRE/GRE-tk-CAT in the presence of RU486. In vivo competition between hPR/RU486 and either cPR/R5020 or the human glucocorticoid receptor/dexamethasone (hGR/Dex) complex further supported that hPR/RU486 bound in vivo to its cognate responsive element. Indeed, the observed inhibition of transcription was shown to be due to competition for the MMTV PRE, since no transcriptional interference by the hPR/RU486 was observed, and since no heterodimers were formed between hPR/RU486 and cPR/R5020 or hGR/Dex. That the ligand-free hPR, however, was unable to compete, demonstrated that ligand binding is the prerequisite for DNA binding of hPR in vivo. PMID- 2249660 TI - Functional analysis of transcribed spacers of yeast ribosomal DNA. AB - Making use of an rDNA unit, containing oligonucleotide tags in both the 17S and 26S rRNA gene, we have analyzed the effect of various deletions in the External Transcribed Spacer (ETS) and in one of the Internal Transcribed Spacers 1 (ITS1) on the process of ribosome formation in yeast. By following the fate of the tagged transcripts of this rDNA unit in vivo by Northern hybridization we found that deleting various parts of the ETS prevents the accumulation of tagged 17S rRNA and its assembly into 40S subunits, but not the formation of 60S subunits. Deleting the central region of ITS1, including a processing site that is used in an early stage of the maturation process, was also found to prevent the accumulation of functional 49 S subunits, whereas no effect on the formation of 60S subunits was detected. The implications of these findings for yeast pre-rRNA processing are discussed. PMID- 2249661 TI - Chromatin structure of transcriptionally competent and repressed genes. AB - We have compared transcriptionally competent and repressed genes with respect to their linker histone content and their ability to fold into higher-order structures. Histones were cross-linked covalently to DNA in chicken erythrocyte and oviduct nuclei by UV irradiation, and the DNA that was immunoprecipitated with anti-H1 and (for erythrocytes) anti-H5 antibodies was analysed for particular DNA sequences. None of the sequences investigated was free of H1 (H5). However, in mature erythrocytes the tissue-specific adult beta-globin gene (beta A) appears to be partially depleted of H5, and both the beta-globin gene and the H5 gene (also tissue-specific), as well as the 'housekeeping' beta-actin gene, appear to be partially depleted of H1 relative to inactive genes; in oviduct slight H1-depletion is detected on the ovalbumin gene relative to genes that are inactive in this tissue and the actin gene. Transcriptionally competent erythrocyte chromatin fragments, in contrast to inactive fragments, are unable to self-associate into 'pseudo-higher-order structures'. This is likely to be a consequence of the partial depletion of H5 and/or H1 in active chromatin, resulting in the breakdown of (probably cooperative) interactions between H5 and/or H1 molecules that otherwise mediate the assembly of pseudo-higher-order structures in vitro and a stable 30 nm chromatin filament in vivo. PMID- 2249662 TI - CPF1, a yeast protein which functions in centromeres and promoters. AB - Centromeres and several promoters of Saccharomyces cerevisiae contain a highly conserved octanucleotide, RTCACRTG, called CDEI. Using biochemical, genetic and structural analyses, we show that the same protein binds in vivo to CDEI sites in centromeres and in promoters. This protein, called CPF1 for centromere promoter factor, binds DNA as a dimer. Inactivation of the gene is not lethal but leads to a partial loss of the centromere function and to a Met- phenotype. Changes of the chromatin structure due to inactivation of CPF1 are seen at centromeres and at several CDEI-carrying promoters (e.g. MET25, TRP1, GAL2). However promoter activities are affected in diverse ways making it presently difficult to describe a function for CPF1 in gene expression. The sequence of the cloned gene reveals in the carboxy-terminal part two potential amphipathic helices preceded by a positively charged stretch of amino acids very similar to the helix-loop-helix domains recently identified in factors controlling tissue specific transcription in higher eukaryotes. Carboxy-terminal truncations of CPF1 lacking this domain no longer bind to CDEI. The amino-terminal half of CPF1 carries two clusters of negatively charged amino acid residues. Surprisingly, deletions of these clusters still render cells Met+ and lead only to a marginal decrease in centromere activity. PMID- 2249663 TI - Mutations altering heat shock specific subunit of RNA polymerase suppress major cellular defects of E. coli mutants lacking the DnaK chaperone. AB - An Escherichia coli mutant lacking HSP70 function, delta dnaK52, is unable to grow at both high and low temperatures and, at intermediate temperature (30 degrees C), displays defects in major cellular processes such as cell division, chromosome segregation and regulation of heat shock gene expression that lead to poor growth and genetic instability of the cells. In an effort to understand the roles of molecular chaperones such as DnaK in cellular metabolism, we analyzed secondary mutations (sid) that suppress the growth defects of delta dnaK52 mutants at 30 degrees C and also permit growth at low temperature. Of the five suppressors we analyzed, four were of the sidB class and mapped within rpoH, which encodes the heat shock specific sigma subunit (sigma 32) of RNA polymerase. The sidB mutations affected four different regions of the sigma 32 protein and, in one case, resulted in a several fold reduction in the cellular concentration of sigma 32. Presence of any of the sidB mutations in delta dnaK52 mutants as well as in dnaK+ cells caused down-regulation of heat shock gene expression at 30 degrees C and decreased induction of the heat shock response after shift to 43.5 degrees C. These findings suggest that the physiologically most significant function of DnaK in the metabolism of unstressed cells is its function in heat shock gene regulation. PMID- 2249664 TI - The AT richness and gid transcription determine the left border of the replication origin of the E. coli chromosome. AB - We have identified novel, cis-acting elements which enhance in vivo the replication activity of plasmids carrying the minimal oriC of Escherichia coli. These are (i) the AT rich sequence ('AT-cluster') which exists immediately left of the 13mer repeats and (ii) the gid transcriptional unit. The 'AT-cluster' was functionally replaced by an unrelated AT rich sequence. This was also the case for the left and middle 13mers; they were substituted by the AT rich fragment from mini-F plasmid. The left 13mer was replaced by the AT rich sequence which did not show the 'reduced helical stability' known as the important character of the 13mer region. In contrast to these results, the right 13mer sequence was strictly required. As to the effect of the transcription from the gid promoter, the minimal oriC was activated only when the transcription was directed away from the left side of it. mioC transcription proceeding toward the oriC had no effect on the activation. Mutations in the DnaA boxes were partially suppressed by gid transcription leaving oriC from the left side. From these results, we propose that the AT richness is a determinant to identify the left border of oriC. It is presumed that gid transcription introduces negative superhelicity at the AT rich region and facilitates DnaA dependent duplex opening. PMID- 2249665 TI - Gene structure of nuclear lamin LIII of Xenopus laevis; a model for the evolution of IF proteins from a lamin-like ancestor. AB - The lamin LIII gene of Xenopus laevis has been characterized. The gene is duplicated in the Xenopus genome. The transcribed region spreads over 22 kb of genomic DNA encoding 12 exons. Two alternatively spliced mRNAs are observed which encode LIII isoforms that differ only by the 12 C-terminal amino acids which, however, both contain the CaaX motif known to be the target of post-translational modifications. The intron pattern of the lamin LIII gene is strikingly similar to that of an invertebrate intermediate filament (IF) gene over the entire protein coding sequence. The similarity in gene structure is restricted to the rod domain when compared with vertebrate types I-III IF genes. Our data suggest a model of how IF proteins evolved from a lamin-like ancestor by deletion of two signal sequences; the nuclear localization signal and the C-terminal ras-related CaaX motif. The data rule out the previously proposed hypothesis that IF proteins evolved from an intronless ancestor with an early divergence of neuronal and non neuronal IF proteins. Together with the data presented in the accompanying paper by Dodemond et al. it can be concluded that the tail domains of lamins and invertebrate IF proteins, but not those of vertebrate IF proteins, are homologous. Thus, the different vertebrate IF proteins probably evolved by combination of the central rod domain with different tail domains by exon shuffling. PMID- 2249666 TI - Structure of an invertebrate gene encoding cytoplasmic intermediate filament (IF) proteins: implications for the origin and the diversification of IF proteins. AB - The structure of the single gene encoding the cytoplasmic intermediate filament (IF) proteins in non-neuronal cells of the gastropod Helix aspersa is described. Genomic and cDNA sequences show that the gene is composed of 10 introns and 11 exons, spanning greater than 60 kb of DNA. Alternative RNA processing accounts for two mRNA families which encode two IF proteins differing only in their C terminal sequence. The intron/exon organization of the Helix rod domain is identical to that of the vertebrate type III IF genes in spite of low overall protein sequence homology and the presence of an additional 42 residues in coil 1b of the invertebrate sequence. Intron position homology extends to the entire coding sequence comprising both the rod and tail domains when the invertebrate IF gene is compared with the nuclear lamin LIII gene of Xenopus laevis presented in the accompanying report of Doring and Stick. In contrast the intron patterns of the tail domains of the invertebrate IF and the lamin genes differ from those of the vertebrate type III genes. The combined data are in line with an evolutionary descent of cytoplasmic IF proteins from a nuclear lamin-like progenitor and suggest a mechanism for this derivation. The unique position of intron 7 in the Helix IF gene indicates that the archetype IF gene arose by the elimination of the nuclear localization sequence due to the recruitment of a novel splice site. The presumptive structural organization of the archetype IF gene allows predictions with respect to the later diversification of metazoan IF genes. Whereas models proposing a direct derivation of neurofilament genes seem unlikely, the earlier speculation of an mRNA transposition mechanism is compatible with current results. PMID- 2249667 TI - Specific association of STOP protein with microtubules in vitro and with stable microtubules in mitotic spindles of cultured cells. AB - STOP (Stable Tubule Only Polypeptide) is a neuronal microtubule associated protein of 145 kd that stabilizes microtubules indefinitely to in vitro disassembly induced by cold temperature, millimolar calcium or by drugs. We have produced monoclonal antibodies against STOP. Using an antibody affinity column, we have produced a homogeneously pure 145 kd protein which has STOP activity as defined by its ability to induce cold stability and resistance to dilution induced disassembly in microtubules in vitro. Western blot analysis, using a specific monoclonal antibody, demonstrates that STOP recycles quantitatively with microtubules through three assembly cycles in vitro. Immunofluorescence analysis demonstrates that STOP is specifically associated with microtubules of mitotic spindles in neuronal cells. Further, and most interestingly, STOP at physiological temperature appears to be preferentially distributed on the distinct microtubule subpopulations that display cold stability; kinetochore-to pole microtubules and telophase midbody microtubules. The observed distribution suggests that STOP induces the observed cold stability of these microtubule subpopulations in vivo. PMID- 2249668 TI - HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure. AB - The HIV-1 trans-activator protein, tat, is an RNA binding protein with a high affinity for a U-rich bulge near the tip of the stem in the RNA stem-loop structure encoded by the trans-activation responsive region (TAR). A Scatchard analysis of tat binding has shown that the purified protein forms a one-to-one complex with HIV-1 TAR RNA with a dissociation constant of Kd = 12 nM. Deletion of the uridine residues in the bulge or substitution with guanine residues produced RNAs with a 6- to 8-fold lower affinity than wild-type TAR. Introduction of a point mutation expected to destabilize base pairing in nearby residues of the TAR stem-loop structure reduced tat binding 10-fold. In contrast, mutations that alter the sequence of the six nucleotide long loop at the tip of TAR RNA structure, and mutations which alter the sequence of the stem whilst preserving Watson-Crick base pairing, do not affect tat binding significantly. There is a direct correlation between the ability of tat to bind to TAR RNA and to activate HIV transcription. Viral LTRs carrying TAR sequences encoding any of the mutations known to produce transcripts which bind tat weakly, are not stimulated efficiently by tat in vivo. PMID- 2249669 TI - A human cell factor is essential for HIV-1 Rev action. AB - To examine the restriction of HIV growth in murine cells, we infected NIH 3T3 cells with HIV pseudotyped by Moloney murine leukemia virus. The virus, which carried a dominant selectable marker under the control of the HIV LTR, gave large numbers of resistant clones, showing that murine cells are permissive for HIV uncoating, reverse transcription, nuclear transport and integration. However, we found that several murine cell lines, as well as CHO cells, could not support the function of rev, the viral regulatory gene which, in human cells, induces the cytoplasmic expression of the incompletely spliced class of HIV mRNAs that encode the viral structural proteins. Transfection of the HIV-infected murine cells with a HTLV-1 rex-expressing vector failed to rescue the rev- phenotype, indicating that the block extended to rex function. Most importantly, we could complement the rev defect by fusing the infected murine with uninfected human cells. We conclude that HIV tropism is partly a consequence of a trans-acting cellular factor critical for Rev function. PMID- 2249670 TI - HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA. AB - Expression of the pX gene products (p40tax, p27rex and p21X-III) of human T cell leukemia virus type 1 (HTLV-1), which is known to be a causative agent of adult T cell lymphoma/leukemia, induces expression of the interleukin-2 receptor alpha chain (IL-2R alpha) on infected T cells. Comparison of IL-2R alpha promoter activities has revealed that the transcriptional activation of the promoter alone cannot explain the large numbers of IL-2R alpha expressed on HTLV-1 infected cells. We found that the rates of the IL-2R alpha mRNA degradation were greatly reduced in pX-positive cells as compared with pX-negative cells. Simultaneous transfection of the expression vector plasmid containing IL-2R alpha cDNA and similar plasmids containing various pX sequences showed that p27rex elongated the half life of IL-2R alpha mRNA. As p27rex did not affect the transport of the IL 2R alpha mRNA from nucleus to cytoplasm, prolongation of the IL-2R alpha mRNA half life by p27rex is ascribed to stabilization of the mRNA. Experiments using deletion mutants and chimeric constructs of the IL-2R alpha cDNA demonstrated that the coding sequence but not the 5' or 3' untranslated region of the IL-2R alpha mRNA sequence is responsible for its protection by p27rex. PMID- 2249671 TI - Frame shift mutations as a novel mechanism for the generation of neutralization resistant mutants of human respiratory syncytial virus. AB - The genetic characterization of four previously reported mutants of human respiratory syncytial (RS) virus resistant to monoclonal antibody 63G is described. Sequences of the G protein genes were obtained from: (i) mRNA derived cDNA recombinants, (ii) direct mRNA sequencing and (iii) amplified vRNA derived cDNAs. The results obtained indicate that the original escape mutants, recovered from individual plaques, contained heterogeneous viral populations. This heterogeneity affected the number of adenosine residues present after nucleotides 588 or 623 of the G protein gene. Mutant viruses recovered after a second plaque purification step generated homogeneous sequences but contained single adenosine insertions or deletions at those two sites compared with the Long sequence. These genetic alterations introduced frameshift changes which are reflected in both the antigenic and structural properties of the mutant G proteins. The origin and importance of frameshift mutations in the RS virus G protein gene are discussed. PMID- 2249672 TI - Molecular analysis of an aurea photosynthetic mutant (Su/Su) in tobacco: LHCP depletion leads to pleiotropic mutant phenotypes. AB - Su is a nuclear encoded, semi-dominant aurea mutation in Nicotiana tabacum L. The homozygous plants (Su/Su) are pale yellow and non-photosynthetic while the heterozygous (Su/+) are photosynthetically competent and have a yellow-green phenotype which is distinct from that of green wild-type plants (+/+). We have examined the RNA and protein levels for a number of nuclear and plastid encoded chloroplast proteins under high and low light plant growth conditions. Under high light conditions, the light-harvesting chlorophyll a/b binding proteins (LHCP) were undetectable in the homozygous Su/Su plants, and the large subunit (LSu) and the small subunit (SSu) of ribulose bisphosphate carboxylase (Rubisco) and cytochrome b559 were severely deficient. However, only the nuclear encoded cab and plastid encoded psbE mRNA (encoding LHCP and cytochrome b559 respectively) were reduced significantly. In heterozygous Su/+ plants, the level of LHCP was reduced to 25% of that in wild-type plants while cab and psbE mRNA, LSu, SSu and cytochrome b559 remained at normal levels, suggesting that LCHP is more immediately affected by the Su mutant gene product than the rest of the photosynthetic proteins and mRNA examined. Under low light conditions, the levels of cab and psbE mRNA, LSu, SSu and cytochrome b559 in homozygous Su/Su plants were equivalent to those in wild-type plants except LHCP which remained undetectable. Similarly, the LHCP level in low light grown Su/+ plants still remained at 25% of wild-type level. These results indicate that the decrease in LHCP is independent of light conditions and has not resulted from photooxidation, whereas the depletion of other proteins and mRNA examined under high light growth conditions is a consequence of photooxidative damage to Su/Su plastids. Furthermore, transgenic Su/Su and Su/+ plants with a cauliflower mosaic virus 35S (CaMV 35S)-cab construct constitutively maintained high levels of cab mRNA but displayed the same pattern of diminished LHCP accumulation as their non transformed counterparts when grown under both high and low light conditions. These results indicate that the Su mutation primarily causes depletion of LHCP. The depletion of LHCP leads to photooxidative damage which results in decreased cab mRNA levels and other pleiotropic lesions in Su/Su plants. PMID- 2249673 TI - The secD locus of E. coli codes for two membrane proteins required for protein export. PMID- 2249675 TI - Survey of burn admissions to the Ethio-Swedish Children's Hospital. AB - A retrospective analysis of burn accidents seen in Ethio-Swedish Children's Hospital, Addis Ababa, Ethiopia over 10 years from January 1978 to December 1987 is presented. A total of 347 cases were seen, accounting for 1.73% of all hospital admissions during the period studied. One hundred eighty-six (53.9%) were males. Scald was the commonest cause, 212 patients (61.1%). Second degree burns involving the extremities were the most frequent. Forty (11.5%) of the patients died. Increased mortality was seen in males with deep third degree burns, shock, a low total protein (less than 6 g%), extensive burns, and burns involving sites other than the extremities. Preventive measures such as educational programmes in schools and on the mass media, together with implementation of legislation to minimize the hazard, are recommended. PMID- 2249674 TI - Preliminary studies on antipyretic and analgesic properties of Taverniera abyssinica. AB - In an attempt to ascertain the pharmacological basis of the use of the marketed traditional drug Taverniera abyssinica A. Rich. (Amharic name Dingetegna), crude extracts as well as purified substances of this plant were tested for their antipyretic and analgesic properties. Antipyretic activity was determined on rats made hyperthermic by yeast injection and analgesic activity was determined by the hot plate, as well as the acetic acid induced writhing, methods. The study showed that the plant possesses significant antipyretic and analgesic activities. PMID- 2249676 TI - Infantile hypertropic pyloric stenosis in a children's hospital a retrospective study. AB - A total of 40 patients with a diagnosis of infantile hypertrophic pyloric stenosis were admitted to Ethio-Swedish Children's Hospital, Addis Ababa, Ethiopia over a period of 6 years (1981-1986). The clinical records of 34 patients could be retrieved and analysed. The incidence rose from 2.7 per thousand admissions in 1981 to 3.6 in 1986. The male to female ratio was 4.7:1. Patients started to vomit at a mean age of 21.5 days with age range from birth to three months. In 26 (76.4%) patients, vomiting started before the first month of life. Their distribution showed a bias towards term infants 97%, males 83.2%, first borns 26.5%, and higher socio-economic class 23.5%. No seasonal variations were observed. A palpable tumor was present in 35.3%. [Each of hematemesis with melena and jaundice were seen in 2.9%]. The treatment was pyloromyotomy; seven patients developed complications but none died. PMID- 2249677 TI - Severe rickets in a children's hospital in Addis Ababa. AB - A retrospective, case-controlled study of rachitic patients admitted to Ethio Swedish Children's Hospital (ESCH), Addis Ababa, Ethiopia, over a ten-year period (1979-1988) is presented. Clinical records of 131 patients with clinical and radiological evidence of rickets and an equal number of randomly selected, age and sex matched controls with no rickets were analysed. Rickets was found to be more common in males (2:1) and at 6 to 18 months of age (79%). Associated findings were infectious diseases (90%), protein-energy malnutrition (75%), anaemia (39%), and congestive heart failure (16). Mortality was much higher in rachitic patients. The admission rates show a progressive increase over the study period. The need for early diagnosis and treatment, continued nutrition and health education, and further study to elucidate the relation between protein energy malnutrition (PEM) and rickets is suggested. PMID- 2249678 TI - Some factors associated with birth weight in Jima, southwestern Ethiopia. AB - A retrospective analysis of factors associated with the birth weights of 1707 singleton live births in Jima Hospital, Southwestern Ethiopia was carried out from Sept. 30, 1986 to August 31, 1988. The mean birth weight was 3183.0 grams (+/- 25.0 grams with 95% confidence); and the incidence of low birth weight was 12.3%. The use of multiple linear regression analysis determined significant independent effects of residence, parity, and sex of the baby on birth weight, while maternal age alone was not significantly (P greater than 0.05) related to birth weight. It is suggested that proper recording and analysis of birth weights be practised, as they are useful in monitoring maternal and child health. PMID- 2249679 TI - Insulin injection technique can be taught without hospitalization. AB - Although hospitalization of the diabetic may be seen as a failure of management, and places the patient in an artificial situation, admission for initiation of insulin therapy is the custom in most Ethiopian hospitals. From January 1987 to January 1988, 144 diabetics were taught insulin injection technique in the Diabetic Clinic of Yekatit 12 Hospital in Addis Ababa, Ethiopia, by two nurses in early morning, six days weekly, sessions. Of these, 85 were inpatients aged 6 to 73 years from all wards, admitted because of ketoacidosis, intercurrent illnesses or rural home. The 59 outpatients, aged 7 to 70 years, attended each morning, and started therapy with 8 to 12 units of Lente insulin daily, the dose being increased every 2 or 3 days by small increments until control was attained. These outpatients needed an average of 4.7 mornings (range 1-13) to learn the technique, and an additional 3 to 4 weeks of frequent checkup to achieve control: several continued their jobs while learning. The method failed with 2 very symptomatic patients; there were no severe hypoglycaemic reactions or other complications. In addition to the financial saving for patients, and reduction of hospital bed use by diabetics, the patients helped and encouraged each other, learning faster than when taught individually as "ill" inpatients. PMID- 2249680 TI - Prolonged paresis in a primigravida during and after caesarean section. AB - A primigravida, who had a Caesarean section because of cervical dystocia and relative cephalo-pelvic disproportion, in Nov. 1988 in Yekatit 12 Hospital, Addis Ababa, remained relaxed and without spontaneous respiration for about four hours after the completion of the operation, requiring assisted respiration. This condition is the result of a decreased plasma cholinesterase (PCE) activity which is responsible for the breaking down of succinylcholine used in general anaesthesia as a muscle relaxant. Although the incidence of PCE deficiency in our population is not known, it should be remembered that such a complication may be seen in hospitals where operations are carried out using succinylcholine as a muscle relaxant. PMID- 2249681 TI - Armauer Hansen Research Institute. A 20-year old experiment. PMID- 2249682 TI - Structural and functional aspects of calcium homeostasis in eukaryotic cells. AB - The maintenance of a low cytosolic free-Ca2+ concentration, ([Ca2+]i) is a common feature of all eukaryotic cells. For this purpose a variety of mechanisms have developed during evolution to ensure the buffering of Ca2+ in the cytoplasm, its extrusion from the cell and/or its accumulation within organelles. Opening of plasma membrane channels or release of Ca2+ from intracellular pools leads to elevation of [Ca2+]i; as a result, Ca2+ binds to cytosolic proteins which translate the changes in [Ca2+]i into activation of a number of key cellular functions. The purpose of this review is to provide a comprehensive description of the structural and functional characteristics of the various components of [Ca2+]i homeostasis in eukaryotes. PMID- 2249683 TI - Myosin heavy chain isoform composition in striated muscle after denervation and self-reinnervation. AB - The total content of myosin heavy chains (MHC) and their isoform pattern were studied by biochemical methods in the slow-twitch (soleus) and fast-twitch (extensor digitorum longus) muscles of adult rat during atrophy after denervation and recovery after self-reinnervation. The pattern of fibre types, in terms of ultrastructure, was studied in parallel. After denervation, total MHC content decreased sooner in the slow-twitch muscle than in the fast-twitch. The ratio of MHC-1 and the MHC-2B isoforms to the MHC-2A isoform decreased in the slow and the fast denervated muscles, respectively. After reinnervation of the slow muscle, the normal pattern of MHC recovered within 10 days and the type 1 isoform increased above the normal. In the reinnervated fast muscle, the 2B/2A isoform ratio continued to decrease. Traces of the embryonic MHC isoform, identified by immunochemistry, were found in both denervated and reinnervated slow and fast muscles. A shift in fibre types was similar to that found in the MHC isoforms. Within 2 months of recovery a tendency to normalization was observed. The results show that (a) MHC-2B isoform and the morphological characteristics of the 2B-type muscle fibres are susceptible to lack of innervation, similar to those of type 1, (b) during muscle recovery induced by reinnervation the MHC isoforms and muscle fibres shift transiently to type 1 in the soleus and to type 2A in the extensor digitorum longus muscles, and (c) the embryonic isoform of MHC may appear in the adult skeletal muscles if innervation is disturbed. PMID- 2249684 TI - Structure of the snake short-chain neurotoxin, erabutoxin c, precursor gene. AB - A 2.4-kb genomic clone, which encodes the precursor of a snake neurotoxin, erabutoxin c, was isolated from the liver of the sea snake, Laticauda semifasciata. The erabutoxin c gene is about 1.2 kb long and consists of three exons and two introns. The first intron is found at the position corresponding to the signal peptide between amino acid residues 18(Leu) and 19(Gly). The second intron is located at the position corresponding to the central loop of the mature toxin, between amino acid residues 33(Arg) and 34(Gly). A TATA box consensus sequence, characteristic of promoter regions, is identified 29-33 nucleotides upstream from the transcription-initiation site identified by nuclease S1 analysis. The erabutoxin c cDNA nucleotide sequence, deduced from the present work, is compared with the cDNA sequences of erabutoxins a and b reported previously. Replacements are found at three positions, two of which correspond to the amino acid replacements found among the toxins, while the other is silent. PMID- 2249685 TI - Partial release of AcPhe-Phe-tRNA from ribosomes during poly(U)-dependent poly(Phe) synthesis and the effects of chloramphenicol. AB - Poly(U)-programmed 70S ribosomes can be shown to be 80% to 100% active in binding the peptidyl-tRNA analogue AcPhe-tRNA to their A or P sites, respectively. Despite this fact, only a fraction of such ribosomes primed with AcPhe-tRNA participate in poly(U)-directed poly(Phe) synthesis (up to 65%) at 14 mM Mg2+ and 160 mM NH4+. Here it is demonstrated that the apparently 'inactive' ribosomes (greater than or equal to 35%) are able to participate in peptide-bond formation, but lose their nascent peptidyl-tRNA at the stage of Ac(Phe)n-tRNA, with n greater than or equal to 2. The relative loss of early peptidyl-tRNAs is largely independent of the degree of initial saturation with AcPhe-tRNA and is observed in a poly(A) system as well. This observation resolves a current controversy concerning the active fraction of ribosomes. The loss of Ac(Phe)n-tRNA is reduced but still significant if more physiological conditions for Ac(Phe)n synthesis are applied (3 mM Mg2+, 150 mM NH4+, 2 mM spermidine, 0.05 mM spermine). Chloramphenicol (0.1 mM) blocks the puromycin reaction with AcPhe-tRNA as expected but, surprisingly, does not affect the puromycin reaction with Ac(Phe)2 tRNA nor peptide bond formation between AcPhe-tRNA and Phe-tRNA. The drug facilitates the release of Ac(Phe)2-4-tRNA from ribosomes at 14 mM Mg2+ while it hardly affects the overall synthesis of poly(Phe) or poly(Lys). PMID- 2249686 TI - Characterization of a novel calcium-binding 90-kDa glycoprotein (BM-90) shared by basement membranes and serum. AB - The protein BM-90 was solubilized from the mouse Engelbreth-Holm-Swarm tumor with neutral buffers in molar yields lower (15-30%) than found for other basement membrane proteins (e.g. laminin, BM-40). The purified protein was shown to be rich in cysteine (5 mol%) and to change in SDS electrophoresis from an 84-kDa position to a 95-kDa one upon reduction. BM-90 was also shown to be a calcium binding protein. The N-terminal sequence of BM-90, as well as those of several internal peptides, showed no identity with any known protein sequences, indicating that it is a new protein. Specific radioimmunoassays showed no or only minor cross-reactions with other known basement membrane proteins. Immunological assays demonstrated BM-90 to be present in neutral salt extracts from mouse heart and kidney, in serum (20-40 micrograms/ml) and in the medium of various cultured cells (0.1-1 microgram/ml). The protein in these samples was identical in size to BM-90 purified from the tumor, indicating that negligible degradation occurs during purification. An extracellular matrix localization of BM-90 was shown by immunofluorescence for Reichert's membrane, lens capsules and other basement membranes. Thus, BM-90 appears to be a novel basement membrane protein whose functions remain to be studied. PMID- 2249687 TI - Binding of ellipticine to beta-lactoglobulin. A physico-chemical study of the specific interaction of an antitumor drug with a transport protein. AB - The unprotonated form of the anti-tumor alkaloid ellipticine binds to beta lactoglobulins A and B from bovine milk with an affinity constant of 7 +/- 3 x 10(5) M-1. There is one binding site/dimeric protein molecule (the stable form at medium pH). The attachment site is not the beta-barrel nor the hydrophobic site identified as the retinol site in beta-lactoglobulin but a domain located at the interface of the two monomeric units where the ligand lies close to Trp61 of both polypeptide chains. The positive binding enthalpy observed in temperature-jump relaxation experiments is overcome by a strong entropy increase, tentatively thought to result from water release at the binding domain. Accordingly, desolvation is assumed to be the rate-determining step in the process of ellipticine binding. PMID- 2249688 TI - Patterns of histone acetylation. AB - The N-terminal domains of all four core histones are subject to reversible acetylation at certain lysine residues. This modification has been functionally linked to transcription, histone deposition at replication and to histone removal during spermatogenesis. To increase understanding of the significance of this modification we have studied the specificity of site utilisation in the monoacetyl, diacetyl and triacetyl forms of histones H3, H4 and H2B (histone H2A has only a single modification site), using pig thymus and HeLa cells as the source of histones. The HeLa histones were extracted from cells grown both with and without butyrate treatment. It is found that for histone H3 there is a fairly strict order of site occupancy: Lys14, followed by Lys23, followed by Lys18 in both pig and HeLa histones. Since the order and specificity is the same when butyrate is added to the HeLa cell cultures, we conclude that addition of the fatty acid does not scramble the specificity of site utilisation, but merely allows more of the natural forms of modified histone to accumulate. For histone H4, the monoacetyl form is exclusively modified at Lys16, but further addition of acetyl groups is less specific and progresses through sites 12, 8 and 5 in an N terminal direction. Similar results were obtained for H4 from both pig thymus and butyrate-treated HeLa cells. Histone H2B could be studied in detail only from butyrate-treated HeLa cells and a much lower level of site specificity was found: sites 12 and 15 were preferred to the more N- and C-terminal sites at Lys5 and Lys20. The data reinforces the view that lysine acetylation in core histones is a very specific phenomenon that plays several functionally distinct roles. The high degree of site specificity makes it unlikely that the structural effects of acetylation are mediated merely by a generalised reduction of charge in the histone N-terminal domains. PMID- 2249689 TI - A study on the regulation of N-glycoloylneuraminic acid biosynthesis and utilization in rat and mouse liver. AB - The relative contribution of N-glycoloyl-beta-D-neuraminic acid (Neu5Gc) to total sialic acids expressed in mouse and rat liver glycoconjugates was found to be 95% and 11%, respectively. This considerable difference in sialic acid composition made these two tissues suitable models for a comparative investigation into the regulation of Neu5Gc biosynthesis and utilization. An examination of the CMP glycoside specificity of Golgi-associated sialyltransferases using CMP-N-acetyl beta-D-neuraminic acid (CMP-Neu5Ac) and CMP-Neu5Gc revealed no significant tissue dependent differences. The Golgi membrane CMP-sialic acid transport system from rat liver did, however, exhibit a slightly higher internalisation rate for CMP Neu5Ac, though no preferential affinity for this sugar nucleotide over CMP-Neu5Gc was observed. In experiments, where Golgi membrane preparations were incubated with an equimolar mixture of labelled CMP-Neu5Ac and CMP-Neu5Gc, no significant tissue-dependent differences in [14C]sialic acid composition were observed, either in the luminal soluble sialic acid fraction or in the precipitable sialic acid fraction, results which are consistent with the above observations. From this experiment, evidence was also obtained for the presence of a Golgi-lumen associated CMP--sialic acid hydrolase which exhibited no apparent specificity for either CMP-Neu5Ac or CMP-Neu5Gc. The specific activity of the CMP-Neu5Ac hydroxylase, the enzyme responsible for the biosynthesis of Neu5Gc, was found to be 28-fold greater in high-speed supernatants of mouse liver than of rat liver. No hydroxylase activity was detected in the Golgi membrane preparations. It is therefore proposed that the cytoplasmic ratio of CMP-Neu5Ac and CMP-Neu5Gc produced by the hydroxylase, remains largely unmodified after CMP-glycoside uptake into the Golgi apparatus and transfer on to growing glycoconjugate glycan chains. The close relationship between the total sialic acid composition and the sialic acid pattern in the CMP-glycoside pools of the tissues lends considerable weight to this hypothesis. PMID- 2249690 TI - Binding sites of a novel neuropeptide pituitary-adenylate-cyclase-activating polypeptide in the rat brain and lung. AB - Pituitary-adenylate-cyclase-activating polypeptide (PACAP) is a novel 38-amino acid neuropeptide isolated from ovine hypothalamic tissues based on its activity of stimulating adenylate cyclase of rat pituitary cells. Binding sites for PACAP were studied in rat tissue membranes using a 27-amino-acid N-terminal derivative of PACAP [PACAP(1-27)] labelled with 125I. Particularly high specific binding sites of 125I-PACAP(1-27) were noted in the hypothalamus, brain stem, cerebellum and lung. Specific binding sites are also present in the pituitary gland, but at a lower concentration, and mainly in the anterior lobe. Very low concentration of 125I-PACAP(1-27)-binding sites were found in the colon, aorta and kidney membranes and no binding sites were detected in the pancreas and testis. Maximal binding of 125I-PACAP(1-27) was observed at pH 7.4. Interaction of 125I-PACAP(1 27) with its binding site was rapid, specific and saturable as well as time, pH and temperature dependent. PACAP(1-27) is more potent than PACAP in displacing the binding of 125I-PACAP(1-27) with brain membranes [concentration that inhibits 50% of the binding (IC50) = 7.45 +/- 1.52 nM and 11.45 +/- 3.65 nM, respectively; mean +/- SEM, n = 4] and lung membranes (IC50 = 4.41 +/- 0.87 nM and 10.68 +/- 3.09 nM, respectively). Vasoactive intestinal peptide displaced the binding of 125I-PACAP(1-27) in lung membrane (IC50 = 16.88 +/- 5.14 nM) but not in brain membranes. The equilibrium binding of 125I-PACAP(1-27) at 4 degrees C was characterized by a single class of binding site for the brain membrane with a dissociation constant (Kd) of 2.46 +/- 0.53 nM and a maximal binding capacity (Bmax) of 8.44 +/- 3.13 pmol/mg protein, but there were two classes of binding site for lung membranes with Kd of 1.02 +/- 0.51 nM and 5.19 +/- 0.99 nM, and Bmax of 2.84 +/- 0.72 pmol/mg protein and 9.13 +/- 1.89 pmol/mg protein, respectively. These findings suggest that subtypes of PACAP-binding sites exist and PACAP may have a physiological role in the hypothalamus/pituitary axis as well as in other regions of the brain and lung. PMID- 2249691 TI - The primary structure of artemin from Artemia cysts. AB - The primary structure of artemin, a major protein isolated from Artemia cysts, has been determined by direct Edman degradation of the purified protein. The amino-terminal acetylated protein has 229 amino acid residues and a high content of histidine and cysteine/cystine. A search in the GenBank Data Base at Los Alamos, using the FASTA program [Pearson, W. R. & Lipman, D. J. (1988) Proc. Natl. Acad. Sci. USA 85, 2444-2448] revealed a limited but unmistakable similarity to ferritin from vertebrates. PMID- 2249692 TI - Molecular cloning of cDNAs for two subunits of rat multicatalytic proteinase. Existence of N-terminal conserved and C-terminal diverged sequences among subunits. AB - cDNA clones for two subunits (designated subunits K and L) of rat liver multicatalytic proteinase (MCP) were isolated using oligonucleotide probes synthesized according to their partial amino acid sequences. The encoded polypeptides of subunits K and L consisted of 255 and 261 amino acid residues with calculated molecular mass of 28.3 kDa and 29.5 kDa, respectively. Northern blot analysis revealed that subunits K and L were expressed in all tissues examined and their expression patterns were almost identical. The deduced amino acid sequences showed no similarities to known protein sequences other than the recently reported sequences of rat and Drosophila MCP subunits. Sequence comparison of MCP subunits of rat and Drosophila revealed that the N-terminal two thirds of the sequence (especially the N-terminal approximately 20 residues) is conserved, but the C-terminal third of the sequence shows no similarity, suggesting functional and structural roles for both regions. Implications for the structural and functional aspects of MCP subunits are discussed based on the sequence similarity. PMID- 2249693 TI - Two-dimensional NMR studies and secondary structure of cobrotoxin in aqueous solution. AB - The 1H-NMR spectra of cobrotoxin, a neurotoxic protein isolated from Formosan cobra Naja naja atra, have been studied by two-dimensional NMR techniques. Of 62 amino acid residues in cobrotoxin, the complete assignments of 58 residues have been made. The resonances from several of the remaining residues have been identified but not yet specifically assigned. The secondary structure of an antiparallel triple- and double-stranded beta-sheet has also been determined by observing the NOE. PMID- 2249694 TI - The collagen-binding site of type-II units of bovine seminal fluid protein PDC 109 and fibronectin. AB - A single type-II domain has been isolated by limited proteolysis of the collagen binding bovine seminal fluid protein, PDC-109. The 45-residue fragment corresponding to the second type-II domain of the parent molecule was found to have retained affinity for immobilized collagen, indicating that this minidomain carries critical regions of the collagen-binding site. Studies on various fragments of fibronectin have also implicated the two type-II units of this molecule in collagen-binding. In the present work we have found that type-II domains of human fibronectin, expressed in Escherichia coli as beta-galactosidase fusion proteins, bind specifically to immobilized collagen. PMID- 2249695 TI - Nuclear-magnetic-resonance studies of human epidermal growth factor. AB - The 1H-NMR spectra of native human epidermal growth factor (EGF) and a derivative lacking the final five residues have been assigned by two-dimensional methods, enabling their structures to be compared. The same structural features are observed for each protein, although the final five residues of native human EGF interact with residues earlier in the sequence. Comparison of the resonance shifts of human, rat and mouse EGF and human transforming growth factor alpha (TGF alpha) enables shifts characteristic of the EGF conformation to be identified, providing standards by which the structures of related proteins may be assessed. PMID- 2249697 TI - Structural characterization of sialylated tetrasaccharides and pentasaccharides with blood group H and Le(x) activity isolated from bovine submaxillary mucin. AB - In this study we have investigated the structures of a sialylated tetrasaccharide and two sialylated pentasaccharides released from bovine submaxillary mucin by alkaline borohydride treatment and isolated by high-performance liquid chromatography. The tetrasaccharide contained NeuGc, while one of the pentasaccharides contained NeuAc and the other contained NeuGc. All three oligosaccharides contained the core type-3 structure (GlcNAc beta 1--- 3GalNAcol). The structures, determined by a combination of one- and two dimensional 1H-NMR spectroscopy at 270 MHz and methylation analysis involving gas liquid chromatography/mass spectrometry, were as follows: [formula: see text]. The oligosaccharides occurred in the approximate molar ratios, 1.0:0.6:0.3. This is the first report of these oligosaccharides in bovine submaxillary mucin. 1H NMR data for structures A1/2c and A1/2e, which are novel structures, are presented for the first time. Oligosaccharide A1/2e contains the blood-group-H type-2 antigenic determinant while oligosaccharide A1/2d contains the Lewis(x) determinant. PMID- 2249696 TI - Radiolabel-transfer cross-linking demonstrates that protein 4.1 binds to the N terminal region of beta spectrin and to actin in binary interactions. AB - Erythrocyte protein 4.1 plays a major role in stabilizing the spectrin-actin junction of the erythrocyte membrane skeleton. The particular sites on spectrin responsible for the binding of actin and protein 4.1 have not been specifically defined, although the general region of the 'tail' end, opposite the self association site, has been deduced by electron microscopy. Using a photoactivatable, radiolabel-transfer cross-linker, 1-[N-(2-hydroxy-5 azidobenzoyl)-2-aminoethyl]-4-(N-hydroxysuccinimidyl)- succinate, we have determined that the binding site for protein 4.1 on spectrin resides in the N terminal region of beta spectrin within a sequence homologous to the actin binding region of alpha actinin. Moreover, this technique provided clear evidence for a direct binding interaction between actin filaments and protein 4.1 that was confirmed by rapid-sedimentation assays. In summary, use of radiolabel-transfer cross-linking has enabled assignment of the protein-4.1-binding site on erythrocyte spectrin and has identified a previously ill-defined binary interaction between protein 4.1 and F-actin. PMID- 2249698 TI - Spectroscopic studies on the metal-ion-binding sites of Co2(+)-substituted D xylose isomerase from Streptomyces rubiginosus. AB - The coordination sphere of the two metal-binding sites/subunit of the homotetrameric D-xylose isomerase from Streptomyces rubiginosus has been probed by the investigation of the Co2(+)-substituted enzyme using electronic absorption, CD and magnetic circular dichroic spectroscopies in the visible region. The spectrum of the high-affinity site (B site) has an absorption coefficient, epsilon 545, of 18 M-1 cm-1, indicating a distorted octahedral complex geometry. The spectrum of the low-affinity site (A site) shows two absorption maxima at 505 nm and 586 nm with epsilon values of 170 M-1 cm-1 and 240 M-1 cm-1, respectively, which indicates a distorted tetrahedral or pentacoordinated complex structure as also observed for the enzyme from Streptomyces violaceoruber [Callens et al. (1988) Biochem. J. 250, 285-290] having the same feature but lower epsilon values. The first 4 mol Co2+ added/mol apoenzyme occupy both sites nearly equally. Subsequently the Co2+ located in the A site slowly moves into the B site. After equilibrium is reached, the next 4 mol Co2+/mol again occupy the A site with its typical spectrum, restoring full activity. Addition of 4 mol Cd2+ or Pb2+/mol Co4-loaded derivative displaces the Co2+ from the B site to form the Pb4/Co4 derivative containing Co2+ in the A site, reducing activity fourfold while the Pb4/Pb4 species is completely inactive. In contrast, Eu3+ displaces Co2+ preferentially from the A site. Thus, the high- and low-affinity sites may be different for different cations. After addition of the substrates D-xylose, D-glucose and D-fructose and the inhibitor xylitol the intense Co2+ A-site spectrum of both the active Co4/Co4 derivative and the less active Pb4/PCo4 derivative decreases, indicating that these compounds are bound to the A site, changing the distorted tetrahedral or pentacoordinated symmetry there to a distorted octahedral complex geometry. PMID- 2249699 TI - Nuclear magnetic resonance studies of sodium/calcium exchange in frog perfused, beating hearts. AB - This study explores the effect of extracellular Ca2+ concentration ([Ca2+]o), on the intracellular Na+ concentration ([Na+]i), in frog intact hearts using nuclear magnetic resonance spectroscopy, which allows for the measurement of [Na+]i in perfused, beating hearts. Decreases in [Ca2+]o yielded marked increases in [Na+]i. A similar effect was seen during inhibition of the Na+/K+ pump and was fully reversible. This sensitivity of [Na+]i to [Ca2+]o, previously observed using microelectrodes, supports a crucial physiological role for Na+/Ca2+ exchange in frog intact, beating hearts. PMID- 2249700 TI - Control of hepatic nitrogen metabolism and glutathione release by cell volume regulatory mechanisms. AB - 1. Urea synthesis was studied in isolated perfused rat liver during cell volume regulatory ion fluxes following exposure of the liver to anisotonic perfusion media. Lowering of the osmolarity in influent perfusate from 305 mOsm/l to 225 mOsm/l (by decreasing influent [NaCl] by 40 mmol/l) led to an inhibition of urea synthesis from NH4Cl (0.5 mmol/l) by about 60% and a decrease of hepatic oxygen uptake by 0.43 +/- 0.03 mumol g-1 min-1 [from 3.09 +/- 0.13 mumol g-1 min-1 to 2.66 +/- 0.12 mumol g-1 min-1 (n = 9)]. The effects on urea synthesis and oxygen uptake were observed throughout hypotonic exposure (225 mOsm/l). They persisted although volume regulatory K+ efflux from the liver was complete within 8 min and were fully reversible upon reexposure to normotonic perfusion media (305 mOsm/l). A 42% inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was also observed when the perfusion medium was supplemented with glucose (5 mmol/l). Urea synthesis was inhibited by only 10-20% in livers from fed rats, and was even stimulated in those from starved rats when an amino acid mixture (twice the physiological concentration) plus NH4Cl (0.2 mmol/l) was infused. 2. The inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was accompanied by a threefold increase of citrulline tissue levels, a 50-70% decrease of the tissue contents of glutamate, aspartate, citrate and malate, whereas 2-oxoglutarate, ATP and ornithine tissue levels, and the [3H]inulin extracellular space remained almost unaltered. Further, hypotonic exposure stimulated hepatic glutathione (GSH) release with a time course roughly paralleling volume regulatory K+ efflux. NH4Cl stimulated lactate release from the liver during hypotonic but not during normotonic perfusion. In the absence of NH4Cl, hypotonicity did not significantly affect the lactate/pyruvate ratio in effluent perfusate. With NH4Cl (0.5 mmol/l) present, the lactate/pyruvate ratio increased from 4.3 to 8.2 in hypotonicity, whereas simultaneously the 3 hydroxybutyrate/acetoacetate ratio slightly, but significantly decreased. 3. Addition of lactate (2.1 mmol/l) and pyruvate (0.3 mmol/l) to influent perfusate did not affect urea synthesis in normotonic perfusions, but completely prevented the inhibition of urea synthesis from NH4Cl (0.5 mmol/l) induced by hypotonicity. Restoration of urea production in hypotonic perfusions by addition of lactate and pyruvate was largely abolished in the presence of 2-cyanocinnamate (0.5 mmol/l). Addition of 3-hydroxybutyrate (0.5 mmol/l), but not of acetoacetate (0.5 mmol/l) largely reversed the hypotonicity-induced inhibition of urea synthesis from NH4Cl.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2249701 TI - Isolation and characterization of two glycoproteins from hyaline cartilage. AB - Two acidic glycoproteins of molecular mass 92 kDa and 56 kDa were purified from 4 M guanidine hydrochloride extracts of chick sternal cartilage, by density gradient centrifugation, ion-exchange chromatography, gel chromatography and SDS/PAGE. The glycoproteins differed in their amino acid and carbohydrate compositions. They were identified by the immunoblotting technique in extracts of chick articular cartilage from various sites and in extracts of cartilage from other species. The proteins are synthesized by the chondrocytes and show a partial cross-reactivity between their antisera. PMID- 2249702 TI - Analysis of wheat-germ RNA polymerase II by trypsin cleavage. The integrity of the two largest subunits of the enzyme is not mandatory for basal transcriptional activity. AB - When wheat-germ RNA polymerase II is subjected to mild proteolytic attack in the presence of trypsin, the resulting form of the enzyme migrates as a single species on electrophoresis in native polyacrylamide gels, with an apparent Mr significantly smaller than that of the native enzyme. Analysis by denaturing gel electrophoresis of the truncated eukaryotic polymerase revealed that the two largest subunits of the native enzyme, i.e. the 220,000-Mr and 140,000-Mr subunits, were cleaved, giving rise to shorter polypeptide chains of Mr 172,800, 155,000, 143,000, 133,800, 125,000 and 115,000. The use of affinity-purified antibodies directed against each of the two large subunits of the native enzyme allowed us to probe for possible precursor/product relationships between the 220,000-Mr and 140,000-Mr subunits of wheat-germ RNA polymerase II and their breakdown products generated in the presence of trypsin. None of the smaller subunits of the plant RNA polymerase II appeared to be sensitive to trypsin attack. The results indicate that the truncated RNA polymerase retained a multimeric structure, and therefore that the proteolyzed largest subunits of the enzyme remained associated with the smaller ones. Furthermore, in transcription of a poly[d(A-T)] template, the catalytic activity of the proteolyzed form of wheat-germ RNA polymerase II was identical to that of the native enzyme. Therefore, the protein domains that can be deleted by the action of trypsin from the two large subunits of the plant transcriptase are not involved in DNA binding and/or nucleotide binding, and do not play an important role in template-directed catalysis of phosphodiester bond formation. PMID- 2249703 TI - Making educational research more important. PMID- 2249704 TI - Mainstream assistance teams: a scientific basis for the art of consultation. AB - The purpose of this investigation was to determine whether a consultant-driven prereferral intervention may be shortened in duration, thereby improving its efficiency, without reducing its effectiveness. Subjects were 60 general educators; their 60 most difficult-to-teach pupils without disabilities; and 22 consultants, representing 17 elementary schools in a large metropolitan school system. The teachers were assigned randomly to a short (n = 24) and long version (n = 24) of the prereferral intervention and to a control group (n = 12). Analyses indicated that the two variants of the prereferral intervention improved teacher perceptions of their difficult-to-teach students and decreased referrals for testing and possible special education placement. Moreover, results suggested that the short and long versions were equally effective. Implications for consultation-related activity are discussed. PMID- 2249705 TI - Instructional behaviors of more and less effective beginning regular and special educators. AB - To enhance understanding of effective teaching, we studied 117 elementary and intermediate secondary general and special educators who were more and less effective in maintaining class participation. We performed MANOVAs on 22 variables associated with positive student outcomes in the process-product literature and found that teachers who maintained higher levels of participation provided effective transitions, made assignments, and approved of students' verbal responses more often than less effective educators. In addition, they demonstrated negative regard less often than less effective teachers. They also acknowledged learner-initiated interactions and employed strategies for managing student inattention and disruption less frequently than teachers who were less effective in maintaining active student involvement. We also found differences in the frequencies with which elementary and secondary teachers and general and special educators exhibited specific behaviors. PMID- 2249706 TI - Educating students with mild disabilities in general education classrooms: Minnesota alternatives. AB - This article reports two major data collection efforts conducted during successive years. Study 1 examined the relationship between the school effectiveness variables identified in the Minnesota Educational Effectiveness Project (MEEP), and the attitudes and achievement of students in 31 MEEP schools. Study 2, which focused on 11 of the Study 1 schools, compared the instructional programs provided to students with mild disabilities in three integrated programs in these 11 schools, with those provided by conventional resource "pull-out" programs in three other schools. We not only contrasted program characteristics, but analyzed differences between program characteristics and cognitive and affective outcomes. Results do not provide a strong basis for concluding that general efforts at school improvement will provide the framework for improved outcomes among low-achieving students. PMID- 2249707 TI - Academic outcomes for students with learning disabilities in consultation and resource programs. AB - In this study, pretest and posttest achievement test data were collected for 67 children with learning disabilities assigned to one of four conditions: one period of resource room instruction per day; two periods of resource room instruction per day; consultative services combined with in-class instruction; and consultative services to classroom teachers. Analysis of pretest achievement measures indicated that students assigned to two periods of resource room per day differed significantly from the other groups and results from this group were analyzed separately. Students in the remaining three conditions made gains in standing relative to same-age peers from pretest to posttest. Students receiving a combination of consultation and direct services showed small, but significantly greater overall gains in achievement than did students placed in the resource room. PMID- 2249708 TI - Mainstream Experiences for Learning Disabled students (Project MELD): preliminary report. AB - Mainstream Experiences for the Learning Disabled (MELD) was developed to accommodate students with learning disabilities in the mainstream. This article reports the progress of 13 students at the end of 1 year of planning and 1 year of implementing the MELD model in one urban elementary school. Observational and school adjustment data from the implementation year suggest that although the MELD model was not fully incorporated into the mainstream classes, students with learning disabilities adjusted well to a less individualized and more demanding mainstream program. They came to school regularly, did not present serious behavior problems, and spent as much of reading class and more of math class on task as they had in special education. These students in the mainstream were assigned more opportunities to work with text materials rather than workbooks in reading and spent significantly more reading time in teacher-directed lessions. Nevertheless, the students made no significant progress in reading or math and earned lower grades during the implementation year. The authors suggest that students with learning disabilities will not succeed in the mainstream if teachers continue "business as usual" in mainstream classes. PMID- 2249709 TI - Human antibody response to fragments A and B of diphtheria toxin and a synthetic peptide of amino acid residues 141-157 of fragment A. AB - Examination of a selection of serum samples from adults from two regions of England showed that 50% of men in the 16-24 years and over 55 years age groups had high titres of antibody to diphtheria toxin (DT). In contrast, only 11% of women aged 16 to over 55 years had high titres of antibody to DT. All human antisera with high anti-DT titres reacted with a synthetic peptide (SP) corresponding to the amino acids 141-157 of DT fragment A, with sera from men aged 35 to over 55 years showing the highest titres. High antibody titres to fragment A paralleled those to SP in both sexes. Titres of antibody to DT fragment B were highest in individuals with high titres to DT. In sera from both sexes immunoglobulin G1 was the predominant subclass reactive with all three antigens. However, both IgG1 and IgG4 and to a lesser extent IgG2 and IgG3 were present in immunoglobulin concentrates. PMID- 2249710 TI - Experimental studies on the comparative infectivity and pathogenicity of Streptococcus suis type 2. I. Porcine and human isolates in pigs. AB - Piglets between 1 and 40 days of age were inoculated with varying numbers and with different isolates of Streptococcus suis type 2 by the intranasal, intravenous and subarachnoid routes. Less than 100 organisms of an isolate cultured from apparently normal pigs caused subclinical infection in 1-day-old piglets after intranasal inoculation. This infection was naturally transmitted between litter mates. Intravenous inoculation of a similar isolate in 7-week-old pigs resulted in a sub-clinical bacteraemia in 3 of 8 piglets. One other piglet developed a bacteraemia 7 days after inoculation and concurrently developed signs of lameness and nervous dysfunction. Ten piglets were inoculated by the subarachnoid route with a porcine isolate and two with an isolate from a person with clinical disease. Only the latter two pigs developed the classical signs of nervous disease associated with infection by S. suis type 2. It is concluded that strains of S. suis type 2, of varying pathogenicity for both pigs and man, are endemic in New Zealand. It is suggested that the occurrence of disease is associated with both exposure to a pathogenic strain and other, as yet undetermined, secondary factors. PMID- 2249711 TI - Experimental studies on the comparative infectivity and pathogenicity of Streptococcus suis type 2. II. Porcine and human isolates in laboratory animals. AB - Mice, rats, guinea-pigs and rabbits were inoculated with isolates of Streptococcus suis type 2. An isolate cultured from the tonsils of a healthy pig, produced disease in rabbits after intravenous inoculation but not in mice, rats or guinea-pigs. An isolate of S. suis type 2, that was pathogenic for pigs and had been cultured from a human patient with clinical disease, produced signs of neurological disease in mice, rats and rabbits following intravenous inoculation. There was an apparent dose response in mice with 31% of mice receiving more than 10(6) organisms developing clinical disease, whilst mice receiving less than this did not develop disease. There were no detectable histopathological lesions in the brains or meninges of mice with nervous signs. It is proposed that the disease in mice may mimic that reported in humans and that mice may be a useful indicator species for determining the virulence of isolates cultured from pigs. PMID- 2249712 TI - Red kidney bean poisoning in the UK: an analysis of 50 suspected incidents between 1976 and 1989. AB - Between July 1976 and February 1989, 50 incidents of suspected red kidney bean poisoning were reported in the UK. Nine incidents in which nausea, vomiting and diarrhoea developed within 1-7 h of ingestion, were confirmed by the detection of haemagglutinin in the beans. The diagnosis was made on a further 23 incidents on the basis of symptoms, incubation time and the description of preparation of beans prior to consumption. The haemagglutinin (lectin), which occurs naturally in the red kidney bean, is inactivated by thorough cooking of well soaked beans. In many of the outbreaks reported the implicated beans were consumed raw or following an inadequate heat process. PMID- 2249713 TI - Crystal violet reactions of fresh clinical isolates of Staphylococcus aureus from two British hospitals. AB - When 168 fresh clinical isolates of Staphylococcus aureus were examined for their reactions on a medium containing 1 part in 100,000 crystal violet 50.6% of strains produced a purple appearance, 39.3% produced a white appearance and 10.1% produced a yellow appearance. Purple-reacting isolates were significantly associated with both invasive infections (P less than 0.01) and hospital origin (P less than 0.001). There were no significant associations between the crystal violet reactions and either animal contact or other properties previously reported to be characteristic of white and yellow-reacting strains (beta haemolysin and bovine coagulase production). The results of phage typing showed associations between susceptibility to group III phages and purple-reacting strains and between phage group II susceptibility and white and yellow-reacting strains. There was also a highly significant association between white reactions on crystal violet agar and susceptibility to lysis by a combination of all three groups (that is, I + II + III) and white-reacting strains were significantly more susceptible to lysis by phages 94 and/or 96, whether as a restricted pattern or as part of a broader pattern. The purple reaction on crystal violet medium may be a reliable marker of the 'hospital staphylococcus'. PMID- 2249714 TI - Diversity studies of Salmonella incidents in some domestic livestock and their potential relevance as indicators of niche width. AB - This study attempts to determine whether or not livestock are becoming more susceptible to epidemics of salmonella infections by the analysis of published data on the annual number of reported infections in various animals. The number of incidents reported each year may be subject to a variety of biases due to temporal and geographical differences in reporting practices. This study analysed these reports by the calculation of diversity indices which are not subject to some of these potential biases. The relationship between the ecological concept of niche width and the diversity of species or types occupying that niche is discussed. The diversity of salmonella types reported in fowl has shown a highly significant decline over the 13-year period 1976-88. It is suggested that this declining diversity may be related to the declining niche width of the biotope available to this pathogen. Although speculative, this reduction in niche width could be related to a declining genetic diversity in the host animals or to an increasing intensification of animal husbandry. PMID- 2249715 TI - Extended phage-typing scheme for Escherichia coli O157:H7. AB - In Canada, the number of human isolates of verotoxigenic (VT + ve) Escherichia coli O157:H7 from diarrhoeal cases and haemolytic uraemic syndrome and haemorrhagic colitis has increased from 25 in 1982 to 2384 in 1989. A total of 3273 VT + ve E. coli O157:H7 strains (3255 strains isolated in Canada and 18 isolates from other countries) were phage typed. The phage typing scheme has been extended from 14 to 62 phage types. Of these, five types occurred exclusively in other countries (type 47 in Japan; and types 49, 50, 51 and 52 in the U.K.). Thirty-five different phage types were identified in Canada; only nine of these (1, 2, 4, 8, 14, 21, 23, 31 and 32), each accounted for more than 1% of the cases from human sources. The same nine types were the only ones observed among the isolates from non-human sources (meat and slaughter houses) suggesting a food borne transmission in most of the human cases. Phage types 1 (30.5%); 4 (21%); 8 (13.5%); 31 (8.9%) and 14 (8%) were encountered in varying frequencies in most of the provinces; infrequently occurring phage types also showed regional variation. Thirteen different phage types were identified among 151 outbreaks representing 556 isolates of E. coli O157:H7. More than one phage type were encountered in 12 outbreaks whereas in 141 outbreaks, all strains in each, had the same phage type. PMID- 2249716 TI - Evaluation of numerical typing systems for Escherichia coli using the API 50 CH and the PhP-EC systems as models. AB - Reproducible and discriminating typing methods are required for epidemiological investigations. Numerical typing systems analyse patterns obtained in various ways by calculating similarity coefficients between isolates. In the present study, various measures of the efficiency of a numerical typing system are quantified. These include reproducibility, accuracy, and discrimination power. Three different numerical typing methods for Escherichia coli were compared using these measures: (a) Biotyping with API 50 CH system, (b) Biochemical fingerprinting with the API 50 CH system and (c) Biochemical fingerprinting with the PhP-EC system. Biotyping qualitatively measures the results of a set of biochemical reactions as + or -. Biochemical fingerprinting also uses biochemical reactions, but the tests are scored quantitatively by measuring the kinetics and intensity of each reaction. It was found that biotyping yielded poor reproducibility. When biochemical fingerprinting analysis was used with the API 50 CHE system the reproducibility and the discrimination was good. The PhP-EC system for biochemical fingerprinting showed equal reproducibility but was superior to the API 50 CH system with regard to discrimination power. PMID- 2249717 TI - Escherichia coli populations from diabetic and non-diabetic patients with bacteraemia and faecal samples from healthy subjects--a comparative study. AB - Biochemical reactions, using the PhP-EC system of biochemical fingerprinting, were evaluated in order to group strains into different clusters and to investigate whether a biochemical typing system may be used to distinguish between randomly selected Escherichia coli strains obtained from bacteraemic patients and healthy controls. Fifty epidemiologically unrelated strains isolated from blood of non-diabetic patients and 46 faecal control strains were studied. Separately, 70 E. coli strains from 64 diabetic patients with bacteraemia were investigated. Diversity index was 0.977, 0.969 and 0.941 respectively. The strains were clustered at a similarity level of 0.95. The bacteraemic and control strains were subdivided into 14 different clusters with 2-12 strains each and 40 'outliers'. The largest cluster was dominated by bacteraemic strains (9/12, 75%). Two other clusters were dominated by control strains. In the remaining groups blood and faecal isolates were evenly distributed. No biochemical test was able to distinguish between bacteraemic and faecal control strains. Strains from patients with diabetes mellitus were grouped in 11 clusters containing 2-14 strains and 22 'outliers'. The low diversity index of bacteraemic strains obtained from diabetic patients as compared to other strains indicated a greater homogenicity. However, no correlation was observed between the examined host factors and the clusters. PMID- 2249718 TI - Differentiation of Achromobacter-like strains from human blood by DNA restriction endonuclease digest and ribosomal RNA gene probe patterns. AB - Variation amongst Achromobacter-like strains was examined by DNA restriction endonuclease digestion and rDNA gene patterns generated using a non-radioactive probe. Chromosomal DNA was extracted from 12 cultures representing Achromobacter groups B, E and F, all from human blood cultures. DNA fingerprinting using EcoRI, Hae III or HindIII sub-divided the strains in a similar manner to that obtained by their protein patterns. The HaeIII patterns, with their small number of bands, were the easiest to interpret. The EcoRI patterns included a species-species triplet of bands but minor band patterns allowed further differentiation. The Achromobacter group F strains comprised a separate taxon and were distinct from the group B and E strains by all techniques examined. The study demonstrates that, in addition to total DNA digest analysis, rDNA gene restriction patterns provide a simple but discriminatory electrophoretic method for distinguishing within Achromobacter groups B and E. PMID- 2249719 TI - Enhanced detection of Candida in blood cultures with the BACTEC 460 system by use of the aerobic-hypertonic (8B) medium. AB - The blood culture records during the 6-year period 1984-9 were reviewed to compare the performance of the BACTEC aerobic (6B) and aerobic-hypertonic (8B) media for the recovery of Candida spp. and Torulopsis glabrata from blood. There were 137 positive blood culture sets that contained both a 6B and an 8B bottle. Sixty-eight different yeasts were recovered from 65 patients including 35 Candida albicans, 19 C. tropicalis, 6 C. parapsilosis, 4 C. krusei, 1 C. pseudotropicalis and 3 Torulopsis glabrata. The 8B medium detected 120 of the positive cultures (87.6%) and was the only positive medium in 35 (25.6%) sets, while the 6B medium detected 102 positive cultures (74.4%) and was the only positive medium in 17 (12.4%) sets (P less than 0.04). For those sets in which both bottles were positive, radiometric detection occurred first in the 8B bottle in 39 sets and first in the 6B bottle in 11 sets (P less than 0.001). The superior performance of the 8B bottle was not related to the administration of amphotericin B. Cultures of stock strains of C. albicans, C. tropicalis, and C. parapsilosis in 6B and 8B media with and without added blood confirmed the finding that 8B was substantially superior to 6B for the detection of candidaemia. It is concluded that an 8B bottle should be included in the blood culture set whenever candidaemia is suspected. PMID- 2249720 TI - Neisseria cuniculi in ruminants: epidemiological aspects. AB - Neisseria cuniculi was isolated, between March 1987 and March 1989, from 38 cases of respiratory disease in small and large ruminants. In all but five cases N. cuniculi was cultured together with other potential respiratory pathogens. A survey was conducted to assess the prevalence of N. cuniculi in the pharyngeal region of Merino and Awassi purebred sheep, Awassi/East-Friesian and Merino/Romanov crossbred sheep and one exotic cross breed (goat/ibex). N. cuniculi was isolated from 80-88% of the animals under 1 month of age. Among older animals, the microorganism was isolated from 20.5% of the pure bred animals and 79.3% of the crossbred ones. This difference was significant (P less than 0.001) by the chi 2 test. The prevalence of N. cuniculi in the second age group coincides with the susceptibility of the breeds to respiratory pathology. This, we believe, is the first report of N. cuniculi involved in multiple cases of respiratory pathology and of a survey assessing the prevalence of this microorganism in small ruminants. PMID- 2249721 TI - Specific IgE response in patients with brucellosis. AB - In the search to find discriminative serological markers to differentiate between patients with acute brucellosis and those with chronic brucellosis, an enzyme linked immunosorbent assay (ELISA) was used to determine and compare the brucella specific IgE response in 80 sera from patients with acute brucellosis, 37 sera from patients with chronic brucellosis, 26 sera from patients with positive blood cultures for bacteria other than brucella and 51 sera from healthy controls. The IgE findings were compared to brucella-specific IgG, IgM, IgA and IgG1-4 demonstrated by ELISA, and to microagglutination test (MAT) results. Elevated (positive) antibrucella IgE titres were detected in 89 and 81% of sera from patients with acute and chronic brucellosis respectively. The predominant antibodies found in patients with acute brucellosis were of the IgG, IgM, IgA, IgE, IgG1 and IgG3 types while in chronic brucellosis IgG, IgA, IgE and IgG4 were found. Although IgE can be detected in patients with brucellosis, it does not discriminate between the acute and chronic stages of the disease. PMID- 2249722 TI - Vaccination campaign against meningococcal disease in army recruits in Italy. AB - A high attack rate (17.3/100,000) of meningococcal disease in army recruits in Italy, with 95% of the cases due to serogroup C, constituted the motivating factors to make bivalent serogroup A + C meningococcal vaccination compulsory by law for army recruits starting January 1987. Because the vaccine was given only to the new recruits entering the army, full coverage was not achieved until January 1988. Nearly 900,000 subjects (300,000 yearly) were vaccinated between January 1987 and December 1989. There were no reports of any untoward reactions to the vaccine. Of the 300,000 recruits in service each year, 52, 21, 15, 5 and 4 cases of the disease occurred in 1985, 1986, 1987, 1988 and 1989, respectively (P less than 0.001). Of the 24 cases occurring since the start of the vaccination, only two (due to serogroup C) were attributable to vaccine failure. The remaining cases were in unvaccinated recruits (15 cases) or were due to serogroups other than A or C (7 cases). The cumulative incidence of meningococcal serogroup C in the 600,000 vaccinated recruits during the period 1988-89 was 0.2/100,000 (1 case amongst 600,000 recruits), while the corresponding figure in the 600,000 unvaccinated recruits during the period 1985-6 was 11.3/100,000 (68 cases amongst 600,000 recruits) (P less than 0.001). The protective efficacy of the vaccine in 1987 was 91.2% (12 cases of meningococcal serogroup A and C disease from an average of 150,000 unvaccinated recruits observed for 1 year, and 1 case from the corresponding average of 150,000 vaccinated ones). In 1988 and in 1989 this figure could not be calculated because all recruits were vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249723 TI - Scabies infestation: the effect of intervention by public health education. AB - The objectives of this study were to determine the prevalence of scabies in an infested village; to educate the residents on self-treatment and prevention by the use of 5% monosulfiram soap; to evaluate the short term effectiveness of this intervention by determining, 2 weeks later, the compliance to self-treatment and prevention; and to determine the prevalence rate on the second visit. In 59 households (96.7% of the village) containing 313 persons, an educational session was held and a leaflet distributed on the use and availability of the soap. Thirteen persons (4.2%) from eight households (13.6%) had scabies. After 2 weeks, 7 persons (2.2%) (2 persisting and 5 new cases) from 5 households (8.5%) were infested. Thus a cure rate of 85% was obtained though the prevalence rate showed no statistically significant difference. Among the under 15 year olds, the numbers infected decreased from 10 to 3 while among the over 15 years olds, the numbers infected increased from 3 to 4, neither reading significance at the 5% level. PMID- 2249724 TI - Acute upper respiratory tract viral illness and influenza immunization in homes for the elderly. AB - Occupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine. Influenza immunization rates by home ranged from 15.4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0.7 upper respiratory episodes per bed per annum with a mortality of 3.4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately 7.50 pounds per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines. PMID- 2249725 TI - Analysis of lens protein synthesis in a cataractous mutant mouse: the Cat Fraser. AB - The cataract produced by the dominant Cat Fraser gene in mouse is associated with quantitative changes in lens proteins (crystallin) and with capsule abnormalities. We have analyzed and compared the protein synthesis in control and mutant lenses using [3H]leucine and [3H]proline incorporation. The specific activities of free [3H]leucine in the intracellular pools of the two mouse strains were identical, while the incorporation of both labelled amino acids in proteins was largely increased in Cat Fraser lens. These data indicate that the higher labelling of Cat Fraser lens proteins reflects a true change in the cellular synthesis activity by Cat Fraser lens cells. Despite the enhanced type IV collagen synthesis by Cat Fraser epithelial cells, the amount of type IV collagen in Cat Fraser capsule is lower than in control. This altered type-IV collagen metabolism may disturb the structure of Cat Fraser capsule which becomes thicker. PMID- 2249726 TI - Prevention of cataracts in pink-eyed RCS rats by dark rearing. AB - Royal College of Surgeons rats have hereditary retinal degeneration and associated posterior subcapsular opacities (PSO) of the lens, detectable by slitlamp at 7-8 postnatal weeks in both pink- and black-eyed rats. The retinal degeneration is intensified by light, especially in pink-eyed rats. A fourth of pink-eyed rats developed mature cataracts by 9-12 months of age, but black-eyed rats whose retinas are protected from light by pigmented irises and pigment epithelium rarely have mature cataracts (3% or less), indicating light may be a factor in cataractogenesis. Prior work had shown that dark rearing reduced the rate of retinal degeneration in pink- but not black-eyed rats, but cataracts were not studied. In the present work, pregnant pink-eyed females were placed in a darkroom 1 week before parturition. Pups were removed over intervals at 20-85 postnatal days for: (a) microscopic study of fresh lenses and of fixed, stained retina and lens, and (b) counts of cells mm-2 of the web-like vitreous cortex after it had been dissected free. The macrophage-like cells are a quantitative index of immune reaction to retinal damage. At 50-53 postnatal days, in pink-eyed cyclic light reared RCS, the mean number of macrophages was 4.6-fold that in congenic controls, but in those that were dark reared it was only 1.4-fold. This was less than the increase in cyclic light reared black-eyed RCS (2.3-fold that in congenic black-eyed controls). Total absence of light reduced retinal degeneration and the number of macrophages, and prevented PSO detectable microscopically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249727 TI - Iris-derived melanocytes contain a growth factor that resembles basic fibroblast growth factor. AB - A melanocyte growth stimulating factor has been purified from bovine iris melanocytes and identified as being closely related to the basic form of fibroblast growth factor (bFGF). This conclusion was based on the behavior of the melanocyte-derived growth factor when submitted to heparin-Sepharose affinity chromatography, as well as on its ability to cross-react with bFGF in radioimmuno and radioreceptor assays. The ability of neutralizing bFGF antibodies to block cell proliferation in response to the melanocyte growth factor further confirms that it is closely related to bFGF. Since melanocytes express the 3.7-kb and 7.0 kb bFGF transcript, the possibility exists that uncontrolled expression of melanocyte-derived bFGF could be involved in the malignant transformation of melanocytes into melanoma cells. PMID- 2249728 TI - Biphasic intraocular pressure response to Q-switched Nd:YAG laser irradiation of the iris and the apparent mediatory role of prostaglandins. AB - In rabbits, laser irradiation of the iris causes an immediate rise in intraocular pressure (IOP), with a concomitant increase of prostaglandins (PGs) in the aqueous humor. We studied IOP responses to Q-switched Nd:YAG laser application to the iris in unanesthetized rabbits, and found that a prolonged IOP reduction lasting for 6-24 hr invariably followed the transient IOP rise of 0.5-2 hr duration. The magnitude of both the IOP rise and reduction was dependent on the level of laser energy. A masked, randomized study revealed that the intraperitoneal administration of indomethacin (50 mg kg-1) prior to laser application significantly reduced the ocular hypertensive and hypotensive responses to laser irradiation (energy: 24 mJ). The maximum IOP rise from baseline was 5.4 +/- 3.0 mmHg (n = 10) with the intraperitoneal vehicle and 1.5 +/- 4.2 mmHg (n = 10) with intraperitoneal indomethacin administration. Thus, the difference was statistically significant (P less than 0.025, Student's t-test). The maximum IOP reduction from baseline was -8.5 +/- 2.6 mmHg (n = 10) with the intraperitoneal vehicle and -4.0 +/- 2.4 mmHg (n = 10) with intraperitoneal indomethacin (P less than 0.001, Student's t-test). The concentration of PGE2 in the aqueous humor, as determined by radioimmunoassay on samples obtained at 2 and 4 hr after laser application, was found to be significantly increased in rabbits that received the vehicle solution but not in animals that were pretreated with intraperitoneal injection of indomethacin. This suggests that this PG or other cyclooxygenase products are involved with mediation of the initial IOP increase and the prolonged decrease in IOP that follows laser irradiation of the iris. PMID- 2249729 TI - Ocular effects of dipivalyl esters of epinephrine and alpha-methylepinephrine. AB - The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and alpha-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-alpha-methylepinephrine (DP alpha meE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DP alpha meE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DP alpha meE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DP alpha meE was more rapid (35-45 min) when compared with DPE (1.5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DP alpha meE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DP alpha meE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DP alpha meE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional alpha-adrenoceptors. It is concluded that DP alpha meE is a potent adrenergic ocular hypotensive agent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249730 TI - Expression of the cell surface antigens RET-PE2 and N-CAM by rat retinal pigment epithelial cells during development and in tissue culture. AB - Invagination of the optic vesicle to form the optic cup results in the formation of two apposed layers of neuroepithelium which follow divergent developmental pathways. Changes in the expression of cell surface molecules may be either the cause or result of important inductive signals during this process. We have used immunological reagents to study the expression of two molecules in the rat: the neural cell adhesion molecule N-CAM, and a cell membrane-associated protein which is specific for pigment epithelium in the adult, RET-PE2. Both N-CAM and RET-PE2 are present in both layers of the optic cup at embryonic age E13, but they become restricted to inner retina and pigment epithelium, respectively, by E17 and maintain that pattern of expression in the normal adult. Culture of pigment epithelial cells results in the reexpression of N-CAM and the continued expression of RET-PE2. Western blotting reveals that the size and relative proportions of the 180- and 140-kDa N-CAM molecules synthesized by rat pigment epithelial cells in vitro differ from that made by rat brain, retina and liver. Embryonic RPE N-CAM contains the sulfated carbohydrate recognized by the HNK-1 antibody, but this epitope was not present on N-CAM synthesized by cultured RPE cells. The reexpression of an embryonic antigen when placed in culture suggests that pigment epithelial cells retain some degree of plasticity in the adult state. PMID- 2249731 TI - Stimulatory effects of prostaglandin D2 analogues on adenylate cyclase in rabbit iris-ciliary body membrane fractions. AB - Effects of prostaglandin (PG) D2 analogues on the adenylate cyclase activity in membrane fractions of the iris-ciliary body complex were studied. PGD2 dose dependently activated the adenylate cyclase with a maximal activity increase of about 60%. The concentration required to cause a half-maximal stimulation (EC50) was about 5 x 10(-7) M. The stimulatory effect of PGD2 was totally dependent on GTP with EC50 for GTP at about 10(-7) M. The rank order of potency of PGD2 analogues for stimulating the adenylate cyclase and BW245C (a selective PGD2 agonist) greater than PGD3 greater than PGD2 greater than 9 beta-PGD2. PGD2 metabolites and PGD2 analogues which have little hypotensive activity were essentially ineffective in stimulating the adenylate cyclase. This rank order was strikingly similar to that reported previously for their intraocular pressure lowering effects. One exception was PGD2 methylester. This compound, though reportedly effective in reducing IOP, failed to activate the adenylate cyclase by itself, presumably because its hypotensive effect is due to its hydrolyzed product, PGD2. These results indicate that the abilities of PGD2 analogues to stimulate the adenylate cyclase of the iris-ciliary body complex in GTP-dependent manner are highly correlated with their ocular hypotensive activities, and suggest that a PGD2 receptor-stimulatory GTP-binding protein-adenylate cyclase complex is involved in the PGD2-induced ocular hypotension. PMID- 2249732 TI - Immunocytochemical evidence for an actin-myosin system in lens epithelial cells. AB - Since filamentous actin had been shown earlier to exist in lens epithelial and fiber cells, we inquired whether this could represent a contractile system with myosin and other actin-associated proteins. We resolved this question in freshly removed or organ-cultured rabbit and squirrel lens epithelial whole mounts using immunocytochemical techniques and by immunoblots of extracts separated by electrophoresis. In the former, methods were developed using long fixation times and long incubation in primary antibodies and biotinylated second antibodies visualized by streptavidin immunofluorescence and by diaminobenzidine peroxidase. Myosin was found to be localized along the filamentous rays and at central vertices of polygonal arrays situated at the apices of epithelial cells. It was not clear whether myosin and actin occurred together along the same or adjacent filaments in a bundle. Tubulin and vimentin were found deeper in the cells and were not aligned with actin and myosin filaments. Control lens epithelia treated similarly except for deletion of the primary antibodies showed no staining. As positive controls, pieces of glycerinated sartorius muscle exhibited characteristic cross-banded patterns of actin and myosin when incubated with the same reagents used on the lens epithelium. Denatured extracts of rabbit lens epithelium and of cortical fiber cells separated by electrophoresis and transferred to nitrocellulose paper, stained specifically with the same myosin and tubulin antibodies used in the immunocytochemistry experiments. The molecular weight profile of the myosin polypeptide indicated that lens tissue has myosin II. We conclude that a contractile system exists in lens epithelial and cortical fiber cells, although the function is not understood at this time. We conjecture that the system may act to stabilize lens shape by providing contractile tone. PMID- 2249733 TI - Qualitative and quantitative analyses of sialic acid in the human trabecular meshwork. AB - By using colloidal iron and polycationic ferritin at low pH (1.8 and 1.9, respectively) as electron histochemical stains, we localized sialic acid moieties in the trabecular meshwork of normal human eyes. The markers were distributed continuously over the entire surface of the trabecular cells, but were localized linearly as well as randomly in the basal lamina. Within the beams, the markers were located irregularly in the collagen core, but were absent from the elastic tissue and from the 100 nm banded structures in the cortical zone. Pretreatment of the tissue with neuraminidase abolished this staining which indicates that sialated moieties are present in the stained structures. Biochemical analysis with the lectin Limax flavus agglutinin revealed that the major sialated polypeptides in individual samples of human trabecular meshwork migrated at apparent molecular weights of 56, 75, 95, 128, 140, 180 and 220 kDa under reducing conditions. The fractions at approximate molecular weights of 180 and 220 kDa include the sialoglycoproteins thrombospondin and fibronectin, respectively. The total content of sialic acid in the human trabecular meshwork (patient age range, 27-57 yr) was 3.6 +/- 0.6 mumol g-1 wet weight, as determined by a colorimetric assay. We conclude that significant quantities of sialic acid are present in the normal human trabecular meshwork as neuraminidase-sensitive alpha-ketosidically linked terminal residues of the polypeptides. PMID- 2249734 TI - Near-infrared Fourier transform Raman spectroscopy in human lens research. PMID- 2249735 TI - Ontogeny and localization of alpha A- and alpha B-crystallins during regeneration of the eye lens. PMID- 2249736 TI - Antibodies to the neural cell adhesion molecule disrupt functional recovery in injured nerves. AB - Tubes containing specific monoclonal antibodies to the neural cell adhesion molecule (N-CAM) were applied to transected sciatic nerves to attempt to perturb the recovery of muscle function. Physiological recordings were used to estimate the return of function. The decline of implanted antibody over 28 days was estimated and negatively correlated with the degree of functional recovery. No significant immune responses were detected in response to the implanted material. The data implicated N-CAM as a significant component of nerve regeneration. PMID- 2249737 TI - Trophic actions of recombinant human nerve growth factor on cultured rat embryonic CNS cells. AB - NGF is a neurotrophic factor for basal forebrain cholinergic neurons and may serve to counteract the cholinergic deficits that are observed in Alzheimer's disease. Prior to the introduction of clinical trials, it is essential that recombinant human NGF (rhNGF) be produced and that its actions on target cells in the CNS be demonstrated. We prepared rhNGF and examined its actions on fetal rat brain neurons in culture including, in particular, the cholinergic neurons of the basal forebrain. rhNGF was more potent in increasing choline acetyltransferase (ChAT) activity in septal cultures than NGF purified from mouse salivary glands (mNGF). ED50s of the beta-NGF dimers were 4.9 pM for rhNGF and 12.4 pM for mNGF. The maximal ChAT activity response was achieved at approximately 35 pM with both NGFs and their efficacies were not significantly different. The two NGFs were not additive in effect. Identical to the results with mNGF, rhNGF strongly enhanced the intensity of ChAT immunostaining in septal cultures. Neither rhNGF nor mNGF affected the appearance of the cultures under phase-contrast illumination. Survival of cells at very low plating density on polyornithine/laminin-coated culture dishes was not affected by rhNGF or mNGF. Protein content and the uptake of GABA were also unaffected. At concentrations of up to 10 micrograms/ml, rhNGF did not significantly increase uptake of dopamine into cultures of ventral mesencephalon. We conclude that rhNGF produces potent and selective actions on cholinergic neurons of the basal forebrain as previously shown for mNGF. PMID- 2249738 TI - Different populations of dorsal lateral geniculate nucleus neurons have concentration-specific requirements for a cortically derived neuron survival factor. AB - A macromolecular fraction of conditioned culture medium (CM) derived from explant cocultures of embryonic rat posterior cortex and caudal thalamus is able to support the survival of neurons in the dorsal lateral geniculate nucleus (dLGN) of newborn rats following ablation of dLGN cortical target areas. In the present study we tested whether the survival-promoting activity of this target-derived neurotrophic agent was concentration dependent and whether different subpopulations of dLGN neurons were equally responsive. With the starting concentration of the CM fraction designated X, increasing concentration results in a progressive falloff in trophic activity so that at 200X overall dLGN survival is similar to that seen in unconditioned medium (UM) controls. In contrast, diluting the fraction produces an increase in activity until maximal survival is achieved at 0.2X. Further dilutions result in a decline in trophic activity until control values are reached at 0.001X. Two populations of neurons within the dLGN, defined by their time of origin, respond in a specific manner to the different concentrations. Neurons generated during the early stages of neurogenesis (E14) have maximal survival (25.8%) at 0.05X, whereas those neurons generated later (E15/16) are maximally supported (30.7% survival) at 10X, a 200 fold difference in concentration. While it is possible that separate neurotrophic and neurotoxic molecules exist for each of these populations of dLGN neurons, the most parsimonious interpretation of the data is that a single cortically derived neurotrophic factor exists whose production is strictly controlled during development to achieve maximal effect on different populations of thalamic neurons that may be functionally distinct. PMID- 2249739 TI - Suppression of sensitivity to change in target disparity during vergence eye movements. AB - It has been demonstrated recently in human psychophysical experiments that sensitivity to surround displacement is suppressed during convergence eye movements. To determine whether sensitivity to changes in target disparity is also reduced, responses to test disparities that were superimposed on standard 4 degrees step disparities were investigated. The test disparities consisted of brief (20 ms) positive and negative pulses as well as steps (in the range of +/- 0.6 degrees). A two-alternative forced-choice procedure was used in which the test disparity was presented in either the first or the second portion of a trial. The results showed that suppression of both test pulse and step disparities began before the start of the convergence movement and continued during the movement. Maximum suppression was about 0.50 to 0.85 log units and occurred between 150 ms before to 50 ms after convergence onset. The differences in sensitivity curves for pulse and step stimuli suggest the presence of different central and peripheral neural factors during vergence eye movements. PMID- 2249740 TI - Mapping study of noradrenergic stimulation of vasopressin release. AB - The precise role of hypothalamic norepinephrine (NE) in the control of vasopressin (AVP) release has remained unclear, due to reports of both inhibitory and excitatory effects of NE and only a few studies with direct hypothalamic manipulations. The present study utilized a chronically implanted swivel brain cannula to investigate, in undisturbed and freely behaving rats, the impact of acute hypothalamic infusions of monoamines on circulating AVP levels. The first study examined and compared the responsiveness of six hypothalamic sites to NE infusion through the swivel cannula. Results indicated that the excitatory effect of central noradrenergic stimulation on serum AVP is highly site specific, localized to the paraventricular (PVN) and supraoptic (SON) nuclei. These two nuclei appeared to be equally responsive to NE infusion, yielding a threefold rise in serum AVP over baseline levels. In contrast, NE in the dorsomedial nucleus produced a significantly smaller increase in AVP, and no response was observed in the ventromedial nucleus, posterior hypothalamus, or perifornical lateral hypothalamus. Further tests conducted in the PVN showed this nucleus to respond in a dose-dependent manner to NE infusion. In contrast, under similar test conditions, dopamine caused only a small increase in AVP at a relatively high dose, while a PVN injection of serotonin produced no response. These results support the existence of an excitatory noradrenergic system controlling AVP release and specifically demonstrate that this function of NE is localized to the PVN and SON, in contrast to other hypothalamic areas, and is mimicked to some extent by dopamine but not by serotonin. PMID- 2249742 TI - When is a father really gone? Paternal-child contact in father-absent homes. AB - This research uses unique longitudinal data to examine the dynamics of the father's presence or absence during a child's first few years of life and consider the extent to which overt father-presence/absence statistics mask a continuing contact with the child's father or other potential father figures. I document the extent to which (1) substantial proportions of children born to younger mothers never have had a biological father residing in the home, (2) "net" levels of fathers' absence at various postbirth points mask significant "gross" flows of fathers in and out of the household, and (3) large proportions of children in homes lacking the biological father have potentially significant contact with absent fathers or new father figures. PMID- 2249741 TI - What's happening to the family? Interactions between demographic and institutional change. PMID- 2249743 TI - Welfare benefits, economic opportunities, and out-of-wedlock births among black teenage girls. AB - This article presents a model of teenage out-of-wedlock births that incorporates the effects of both welfare and nonwelfare economic opportunities. We construct measures of the likely "medium-run" income available to a teenage girl in the event of an out-of-wedlock birth and in the absence of a birth and then estimate a logit model to determine their importance in influencing fertility behavior. The model is estimated with data from the Panel Study of Income Dynamics on nearly 900 black teenagers. We find weak and statistically insignificant positive effects of Aid to Families With Dependent Children (AFDC) benefit levels and stronger and significant negative effects of economic opportunities on the probability of AFDC-related out-of-wedlock teen births. PMID- 2249744 TI - Adolescent sexual activity in the family context: the impact of older siblings. AB - Using approximately 2,000 sibling pairs from the National Longitudinal Survey of Labor Market Experience of Youth, we examine the influence of an older sibling's age at first sexual intercourse on the sexual initiation of a younger sibling. Hypotheses about differences by gender composition of the pair are tested, using a framework derived from social comparison theory and a two-stage failure-time model. Results provide evidence of a direct but modest-sized older sibling effect for white but not black youth. This effect is approximately equal in magnitude for same- and opposite-sex siblings. Little support is offered for the greater salience and association of sexual activity for brother-brother as compared with sister-sister pairs. PMID- 2249746 TI - Fertility desires and fertility: hers, his, and theirs. AB - The relationship between desired and achieved fertility may be misspecified by excluding husbands' fertility desires or by confounding effects of shared desires with the resolution of conflicting desires. Using couple data from the classic Princeton Fertility Surveys, we find relatively large husband effects on fertility outcomes as well as unique effects of spousal disagreement. Wives and husbands were equally likely to achieve fertility desires, and disagreeing couples experienced fertility rates midway between couples who wanted the same smaller or larger number of children. These conditions do not hold, however, when we include willingness to delay births for economic mobility as part of the measure of fertility desires. Among couples who both wanted a third child, only husbands' willingness to delay births had significant negative effects on birth rates. PMID- 2249745 TI - Determinants of contraceptive switching behavior in rural Sri Lanka. AB - This study examines the influence of a selected set of determinants of contraceptive method switching in rural Sri Lanka. Of interest is the question of how change in contraceptive practice at the individual level can account for patterns observed at the aggregate level. Based on calendar data on contraceptive use over a 3-year period, collected for more than 3,000 married women in a 1986 survey, the multivariate analysis shows that women who attain all or a significant proportion of their desired fertility tend to switch to more effective methods. Women who experience method failure tend to switch methods, usually to a type that is more effective. The woman's background determinants of age and education have small but significant effects on method switching, whereas the effect of household economic well-being is not significant. There is strong indication that rural couples are practicing contraception in a nonrandom fashion, switching methods in accordance with changes in their fertility motivations and contraceptive experience. PMID- 2249747 TI - Residential preferences and population redistribution: 1972-1988. AB - In seeking to explain recent trends in population distribution, there has been increased interest in residential preferences. This study is a comparison of preferences based on 1972 and 1988 national surveys, years that bracket a period of considerable change in distribution patterns. Over time there has been a small shift in preference toward cities less than 500,000 in size, primarily by those already living there. Rural settings, especially near cities, continue to be very attractive. At both times studied, more than half of those preferring a smaller or more remote place would retain this preference even if it meant 10% less income. Nevertheless, the proportion preferring to live more than 30 miles from a large city was unchanged and approximately equal to the proportion already living there at both times, indicating that a discrepancy between where people live and where they want to live is not an important basis for the upturn in nonmetropolitan growth away from large cities in the 1970s or the downturn in the 1980s. PMID- 2249749 TI - Recent trends in the process of stratification. AB - Using the 14 annual cross-sections from the General Social Survey, we specify a "basic model" of attainment and describe the year-by-year fluctuations in its parameters. The results are partially consistent with theories describing the gradual growth of universalistic patterns of stratification and mobility. Under a linear model of educational achievement, we find that the direct effects of race are weakening and the returns to class-based advantages are declining in tandem. The contours of the socioeconomic "gender gap" are also changing in important ways, with the male intercept declining at a rapid pace and the female term registering small and insignificant year-by-year gains. At the same time, the returns to experience and schooling are increasing for men, whereas the corresponding returns for women have remained stable over the 15-year period. This pattern of interaction effects implies that the size of the gender gap varies over time and across different population groups. PMID- 2249748 TI - Rural-to-urban migration and child survival in Senegal. AB - Analysis of the 1986 Senegal Demographic and Health Survey reveals that mothers may be able to improve their children's survival chances by migrating from the countryside to the city. Children of urban migrants, however, continue to experience a much higher risk of mortality before the age of 5 than children of urban nonmigrants, even after the mother has lived in the city for several years. This migrant mortality disadvantage persists when controlling for numerous socioeconomic and fertility-related factors typically associated with child mortality in developing countries, which also serve as indicators of migrant selection and adaptation. PMID- 2249750 TI - Alternative projections of the U.S. population. AB - The U.S. Bureau of the Census recently released a set of population projections that include middle and high projections that we argue are too conservative. The projections discount the possibility of future baby booms and assume slow rates of mortality decline and low levels of immigration. In this article we explore the impact on the size and age composition of the U.S. population of alternative scenarios of plausible fertility, mortality, and immigration assumptions. We conclude that (1) the Census Bureau's highest projection might be interpreted as a reasonable middle projection, (2) a reasonable high projection would yield a U.S. population in 2080 some 300 million persons larger than the Bureau's highest projection, with the population 85 and older more than twice the Bureau's greatest estimate, and (3) uncertainty about the pace of population growth is substantially greater than the Bureau's projections suggest. PMID- 2249751 TI - Reproductive stopping rules and Lexian variation: a comment on Yamaguchi (1989). PMID- 2249752 TI - Genes and development: molecular and logical themes. PMID- 2249753 TI - Further tests of a recombination model in which chi removes the RecD subunit from the RecBCD enzyme of Escherichia coli. AB - When one of two infecting lambda phage types in a replication-blocked cross is chi + and DNA packaging is divorced from the RecBCD-chi interaction, complementary chi-stimulated recombinants are recovered equally in mass lysates only if the chi + parent is in excess in the infecting parental mixture. Otherwise, the chi 0 recombinant is recovered in excess. This observation implies that, along with the chi 0 chromosome, two chi + parent chromosomes are involved in the formation of each chi + recombinant. The trimolecular nature of chi + stimulated recombination is manifest in recombination between lambda and a plasmid. When lambda recombines with a plasmid via the RecBCD pathway, the resulting chromosome has an enhanced probability of undergoing lambda x lambda recombination in the interval into which the plasmid was incorporated. These two observations support a model in which DNA is degraded by Exo V from cos, the sequence that determines the end of packaged lambda DNA and acts as point of entry for RecBCD enzyme, to chi, the DNA sequence that stimulates the RecBCD enzyme to effect recombination. The model supposes that chi acts by ejecting the RecD subunit from the RecBCD enzyme with two consequences. (1) ExoV activity is blocked leaving a highly recombinagenic, frayed duplex end near chi, and (2) as the enzyme stripped of the RecD subunit travels beyond chi it is competent to catalyze reciprocal recombination. PMID- 2249754 TI - A defect in mismatch repair in Saccharomyces cerevisiae stimulates ectopic recombination between homeologous genes by an excision repair dependent process. AB - Null mutations in three recombination and DNA repair genes were studied to determine their effects on mitotic recombination between the duplicate AdoMet (S adenosylmethionine) synthetase genes (SAM1 and SAM2) in Saccharomyces cerevisiae. SAM1 and SAM2, located on chromosomes XII and IV, respectively, encode functionally equivalent although differentially regulated AdoMet synthetases. These similar but not identical (homeologous) genes are 83% homologous at the nucleotide level and this identity is limited solely to the coding regions of the genes. Single frameshift mutations were introduced into the 5' end of SAM1 and the 3' end of SAM2 by restriction site ablation. The sequences surrounding these mutations differ significantly in their degree of homology to the corresponding area of the other gene. Mitotic ectopic recombination between the mutant sam genes occurs at a rate of 8.4 x 10(-9) in a wild-type genetic background. Gene conversion of the marker within the region of greater sequence homology occurs 20 fold more frequently than conversion of the marker within the region of relative sequence diversity. The relative orientation of the two genes prevents the recovery of translocations. Mitotic recombination between the sam genes is completely dependent on the DNA repair and recombination gene RAD52. A mutation in PMS1, a mismatch repair gene, causes a 4.5-fold increase in the rate of ectopic recombination. RAD1, an excision repair gene, is required to observe this increased rate of ectopic conversion. In addition, RAD1 is involved in modulating the pattern of coconversion during recombination between the homeologous sam genes. These results suggest that interactions between mismatch repair, excision repair and recombinational repair functions are involved in determining the ectopic gene conversion frequency between the sam genes. PMID- 2249755 TI - The translational activator GCN3 functions downstream from GCN1 and GCN2 in the regulatory pathway that couples GCN4 expression to amino acid availability in Saccharomyces cerevisiae. AB - The GCN4 protein of S. cerevisiae is a transcriptional activator of amino acid biosynthetic genes which are subject to general amino acid control. GCN3, a positive regulator required for increased GCN4 expression in amino acid-starved cells, is thought to function by antagonism of one or more negative regulators encoded by GCD genes. We isolated gcn3c alleles that lead to constitutively derepressed expression of GCN4 and amino acid biosynthetic genes under its control. These mutations map in the protein-coding sequences and, with only one exception, do not increase the steady-state level of GCN3 protein. All of the gcn3c alleles lead to derepression of genes under the general control in the absence of GCN1 and GCN2, two other positive regulators of GCN4 expression. This finding suggests that GCN3 functions downstream from GCN1 and GCN2 in the general control pathway. In accord with this idea, constitutively derepressing alleles of GCN2 are greatly dependent on GCN3 for their derepressed phenotype. The gcn3c alleles that are least dependent on GCN1 and GCN2 for derepression cause slow growth under nonstarvation conditions. In addition, all of the gcn3c alleles are less effective than wild-type GCN3 in overcoming the temperature-sensitive lethality associated with certain mutations in the negative regulator GCD2. These results suggest that activation of GCN3 positive regulatory function by the gcn3c mutations involves constitutive antagonism of GCD2 function, leading to reduced growth rates and derepression of GCN4 expression in the absence of amino acid starvation. PMID- 2249756 TI - Meiosis in asynaptic yeast. AB - The Saccharomyces cerevisiae red1 mutant fails to assemble synaptonemal complex during meiotic prophase. This mutant displays locus-specific reductions in interchromosomal gene conversion and a moderate reduction in crossing over. The occurrence of a significant amount of meiotically induced recombination in the red1 mutant indicates that the synaptonemal complex is not absolutely required for meiotic exchange. The RED1 gene product is required for intrachromosomal recombination in some assays but not others. Chromosomes that have undergone reciprocal exchange nevertheless nondisjoin in red1 mutants, indicating that crossovers are not sufficient for disjunction. Epistasis studies reveal that HOP1 is epistatic to RED1, and that RED1 acts in an independent pathway from MER1. A model for the function of the RED1 gene product in chromosome synapsis is discussed. PMID- 2249757 TI - Mitochondrial genetics in a natural population of the plant pathogen armillaria. AB - Transmission and propagation of mitochondrial genotypes in fungi have not been previously investigated in the field. This study examined the distribution of nuclear and mitochondrial genotypes in a natural, local population of the fungal (Basidiomycetes) root-rot pathogen, Armillaria. Six vegetative clones, ranging in size up to 635 m, were identified on the basis of mating-type alleles. Mitochondrial DNA (mtDNA) restriction fragment patterns indicated that each vegetative clone has one, unique mtDNA type. However, as in other basidiomycetous fungi, biparental transmission of mitochondria following laboratory matings of sexually compatible haploid isolates of Armillaria resulted in a uniformly diploid mycelium that was a mosaic for both parental mitochondrial types. Therefore, either matings between monosporous, haploid isolates are uncommon in nature, or when mating does occur, cytoplasmic markers of one partner predominate during subsequent vegetative growth. PMID- 2249758 TI - Essential genes in the hDf6 region of chromosome I in Caenorhabditis elegans. AB - In this paper we describe the analysis of essential genes in the hDf6 region of chromosome I of Caenorhabditis elegans. Nineteen complementation groups have been identified which are required for the growth, survival or fertility of the organism (essential genes). Since ten of these genes were represented by more than one allele, a Poisson calculation predicts a minimum estimate of 25 essential genes in hDf6. The most mutable gene in this region was let-354 with seventeen alleles. An average mutation rate of 5 x 10(-5) mutations/gene/chromosome screened was calculated for an ethyl methanesulfonate dose of 15 mM. Mutations were recovered by screening for lethal mutations using the duplication sDp2 for recovery. Our analysis shows that duplications are very effective for maintenance and mapping of large numbers of lethal mutations. Approximately 600 lethal mutations were mapped in order to identify the 54 that are in the deficiency hDf6. The hDf6 region appears to have a lower proportion of early arresting mutations than other comparably sized regions of the genome. PMID- 2249759 TI - Mutations affecting the meiotic and mitotic divisions of the early Caenorhabditis elegans embryo. AB - We describe interactions between maternal-effect lethal mutations in four genes of Caenorhabditis elegans whose products appear to be involved in the meiotic and mitotic divisions of the one-cell embryo. Mitosis is disrupted by two dominant temperature-sensitive gain-of-function maternal-effect lethal mutations, mei 1(ct46) and mel-26(ct61), and by recessive loss-of-function maternal-effect lethal mutations of zyg-9. The phenotypic defects resulting from these mutations are similar. Doubly mutant combinations show a strong enhancement of the maternal effect lethality under semipermissive conditions, suggesting that the mutant gene products interact. We isolated 15 dominant suppressors of the gain-of-function mutation mei-1(ct46). Thirteen of these suppressors are apparently intragenic, but 11 of them suppress in trans as well as cis. Two extragenic suppressors define a new gene, mei-2. The suppressor mutations in these two genes also result in recessive maternal-effect lethality, but with meiotic rather than mitotic defects. Surprisingly, most of these suppressors are also able to suppress mel 26(ct61) in addition to mei-1(ct46). The products of the four genes mei-1, mei-2, zyg-9 and mel-26 could be responsible for some of the specialized features that distinguish the meiotic from the mitotic divisions in the one-cell embryo. PMID- 2249760 TI - The exuperantia gene is required for Drosophila spermatogenesis as well as anteroposterior polarity of the developing oocyte, and encodes overlapping sex specific transcripts. AB - The Drosophila gene exuperantia (exu) is a maternal effect gene which is needed for proper localization of the bcd RNA during the formation of oocytes. We have extended the characterization of the exu phenotype and find that the gene functions in the male as well as the female germline. Six of seven exu alleles are male-sterile; mutant defects in spermatogenesis first appear during meiosis. A genetic analysis presented here shows that the exu gene does not encode a zygotic vital function. The isolation of two overlapping deficiencies that delete exu function localizes the gene cytologically to polytene bands 57A4-B1. We describe the molecular cloning and identification of the gene, and show that it encodes overlapping sex-specific transcripts of 2.9 kb in the male and 2.1 kb in the female. We also show that these two transcripts are limited in expression to the germline. We demonstrate that one allele, exuVL57, is a deletion of about 700 bp which results in a loss of both transcripts. PMID- 2249761 TI - A hybrid dysgenesis syndrome in Drosophila virilis. AB - A new example of "hybrid dysgenesis" has been demonstrated in the F1 progeny of crosses between two different strains of Drosophila virilis. The dysgenic traits were observed only in hybrids obtained when wild-type females (of the Batumi strain 9 from Georgia, USSR) were crossed to males from a marker strain (the long established laboratory strain, strain 160, carrying recessive markers on all its autosomes). The phenomena observed include high frequencies of male and female sterility, male recombination, chromosomal nondisjunction, transmission ratio distortion and the appearance of numerous visible mutations at different loci in the progeny of dysgenic crosses. The sterility demonstrated in the present study is similar to that of P-M dysgenesis in Drosophila melanogaster and apparently results from underdevelopment of the gonads in both sexes, this phenomenon being sensitive to developmental temperature. However, in contrast to the P-M and I-R dysgenic systems in D. melanogaster, in D. virilis the highest level of sterility (95-98%) occurs at 23-25 degrees. Several of the mutations isolated from the progeny of dysgenic crosses (e.g., singed) proved to be unstable and reverted to wild type. We hypothesize that a mobile element ("Ulysses") which we have recently isolated from a dysgenically induced white eye mutation may be responsible for the phenomena observed. PMID- 2249762 TI - Genetics of 51D-52A, a region containing several maternal-effect genes and two maternal-specific transcripts in Drosophila. AB - Two genomic clones exhibiting a maternal-specific pattern of expression map to cytological region 52A. To elucidate the function of these clones we have undertaken a mutagenesis of the cytological region 51D-52A. This paper presents the results of this screen and the preliminary analysis of female-sterile and lethal mutations isolated. A total of twelve complementation groups have been identified, four of which are defined exclusively by female-sterile alleles. Only one visible mutation was isolated, a recessive temperature-sensitive allele of Thickened-arista (Tarts). Several of the seven lethal loci display an embryonic lethal phase. Three of the four female-sterile loci affect chorion structure with one resulting in underamplification of the chorion genes, and two (possibly three) of the four female-steriles affect nuclear division/DNA replication. Thus it appears that this is a "developmentally important" region, possibly representing a clustering of genes involved in either DNA replication or nuclear division. PMID- 2249763 TI - "Sex ratio" meiotic drive in Drosophila testacea. AB - We document the occurrence of "sex ratio" meiotic drive in natural populations of Drosophila testacea. "Sex ratio" males sire greater than 95% female offspring. Genetic analysis reveals that this effect is due to a meiotically driven X chromosome, as in other species of Drosophila in which "sex ratio" has been found. In contrast to other drosophilids, the "sex ratio" and standard chromosomes of D. testacea do not differ in gene arrangement, implying that the effect may be due to a single genetic factor in this species. In all likelihood, the "sex ratio" condition has evolved independently in D. testacea and in the Drosophila obscura species group, as the loci responsible for the effect occur on different chromosomal elements. An important ecological consequence of "sex ratio" is that natural populations of D. testacea exhibit a strong female bias. Because D. testacea mates, oviposits, and feeds as adults and larvae on mushrooms, this species provides an excellent opportunity to study the selective factors in nature that prevent "sex ratio" chromosomes from increasing to fixation and causing the extinction of the species. PMID- 2249765 TI - Recombination in the B chromosome of maize to produce A-B-A chromosomes. AB - The translocations between the supernumerary B chromosomes and the normal A chromosomes of maize provide a valuable tool for gene localizations, dosage studies and characterization of mutants as null, leaky or gain-of-function. A procedure is described, that relies on recombination in the B chromosome, for marking each of the various B-A translocations with a single dominant marker that will allow dosage classifications of individuals at the mature kernel stage. This marker is R-scm3, which conditions anthocyanin pigment in the aleurone of the endosperm and the scutellum of the embryo. A test for recombination in the B chromosome was conducted by crossing together two translocations, that were broken on opposite sides of the B centromere, and in different A chromosome arms, namely TB-1La and TB-10L18. An example was recovered that linked genetic markers on 1L and 10L to the B centromere. Cytological examination at pachytene of meiosis confirmed the new chromosomal linkage. The use of this procedure to produce a comprehensive set of uniformly marked B-A translocations is discussed. PMID- 2249764 TI - Incomplete maternal transmission of mitochondrial DNA in Drosophila. AB - The possibility of incomplete maternal transmission of mitochondrial DNA (mtDNA) in Drosophila, previously suggested by the presence of heteroplasmy, was examined by intra- and interspecific backcrosses of Drosophila simulans and its closest relative, Drosophila mauritiana. mtDNAs of offspring in these crosses were characterized by Southern hybridization with two alpha-32P-labeled probes that are specific to paternal mtDNAs. This method could detect as little as 0.03% paternal mtDNA, if present, in a sample. Among 331 lines that had been backcrossed for ten generations, four lines from the interspecific cross D. simulans (female) x D. mauritiana (male) showed clear evidence for paternal leakage of mtDNA. In three of these the maternal type was completely replaced while the fourth was heteroplasmic. Since in this experiment the total number of fertilization is known to be 331 x 10 = 3310, the proportion of paternal mtDNA per fertilization was estimated as about 0.1%. The mechanisms and evolutionary significance for paternal leakage are discussed in light of this finding. PMID- 2249767 TI - Use of a controlled-nutrient experiment to test heterosis hypotheses. AB - A controlled-nutrient (CN) experiment was conducted to test three heterosis hypotheses with reference to tomato yield, and its components, for a set of two inbred lines and their hybrid that had previously exhibited considerable heterosis under field conditions. The CN treatments consisted of periodic applications of differential doses of nutrient solution to plants reared individually in containers filled with vermiculite. Ripe fruit were harvested, counted and weighed over a period of 340 days. The data permitted the partitioning of yield into a closed system of five component variables. Heterosis was not exhibited by yield, nor yield components, at any of the four nutrient levels. Hence the total heterosis phenomenon was classified as nutrient dependent: heterosis occurring under field conditions, but not under the nutritional restrictions of the CN experiment. Three heterosis hypotheses were examined for their ability to explain all of the nutrient-dependent aspects of the heterosis phenomenon. Hypothesis 1: Heterosis is a consequence of a more efficient hybrid metabolic system in that it can produce more product with equal input. Hypothesis 2: Heterosis is a consequence of the somatic multiplication of additive component traits. Hypothesis 3: Heterosis is a consequence of a faster hybrid growth rate. Although none of the hypotheses are rejected by the field data, the first two are rejected by the CN experimental results. The third hypothesis fits all aspects of the nutrient-dependent heterosis phenomenon remarkably well. It is speculated that the indeterminate pattern of plant development responsible for yield and its components is due to two major gene systems: genes that determine morphogenetic, and genes that determine growth rate manifestations of growth. Under this hypothesis, the CN technique permits separation of the responses due to these two gene systems. PMID- 2249766 TI - Genetic and molecular organization of ribosomal DNA (rDNA) variants in wild and cultivated barley. AB - Twenty rDNA spacer-length variants (slvs) have been identified in barley. These slvs form a ladder in which each variant (with one exception) differs from its immediate neighbors by a 115-bp subrepeat. The 20 slvs are organized in two families, one forming an eight-step ladder (slvs 100-107) in the nucleolus organizer region (NOR) of chromosome 7 and the other a 12-step ladder (slvs 108a 118) in the NOR of chromosome 6. The eight shorter slvs (100-107) segregate and serve as markers of eight alleles of Mendelian locus Rrn2 and the 12 longer slvs (108a-118) segregate and serve as markers of 12 alleles of Mendelian locus Rrn1. Most barley plants (90%) are homozygous for two alleles, including one from each the 100-107 and the 108a-118 series. Two types of departures from this typical pattern of molecular and genetic organization were identified, one featuring compound alleles marked by two slvs of Rrn1 or of Rrn2, and the other featuring presence in Rrn1 of alleles normally found in Rrn2, and vice versa. The individual and joint effects on adaptedness of the rDNA alleles are discussed. It was concluded that selection acting on specific genotypes plays a major role in molding the strikingly different allelic and genotypic frequency distributions seen in populations of wild and cultivated barley from different ecogeographical regions. PMID- 2249768 TI - Using molecular markers to estimate quantitative trait locus parameters: power and genetic variances for unreplicated and replicated progeny. AB - Many of the progeny types used to estimate quantitative trait locus (QTL) parameters can be replicated, e.g., recombinant inbred, doubled haploid, and F3 lines. These parameters are estimated using molecular markers or QTL genotypes estimated from molecular markers as independent variables. Experiment designs for replicated progeny are functions of the number of replications per line (r) and the number of replications per QTL genotype (n). The value of n is determined by the size of the progeny population (N), the progeny type, and the number of simultaneously estimated QTL parameters (q - 1). Power for testing hypotheses about means of QTL genotypes is increased by increasing r and n, but the effects of these factors have not been quantified. In this paper, we describe how power is affected by r, n, and other factors. The genetic variance between lines nested in QTL genotypes (sigma 2n:q) is the fraction of the genetic variance between lines (sigma 2n) which is not explained by simultaneously estimated intralocus and interlocus QTL parameters (phi 2Q); thus, sigma 2n:q = sigma 2n - phi 2Q. If sigma 2n:q not equal to 0, then power is not efficiently increased by increasing r and is maximized by maximizing n and using r = 1; however, if sigma 2n:q = 0, then r and n affect power equally and power is efficiently increased by increasing r and is maximized by maximizing N.r. Increasing n efficiently increases power for a wide range of values of sigma 2n:q.sigma 2n:q = 0 when the genetic variance between lines is fully explained by QTL parameters (sigma 2n = phi 2Q).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2249769 TI - A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. AB - Naturally occurring deletions that remove sequences located approximately 60 kb upstream of the human adult beta-globin gene result in the failure to transcriptionally activate the cis-linked globin genes in erythroid cells. In addition, transfection, transgenic, and somatic cell hybrid studies have revealed that sequences within this region are essential for the developmentally regulated high-level expression of cis-linked globin genes. This regulatory region located at the 5' end of the beta-globin locus has been termed the locus activation region (LAR). Using somatic cell hybrids, we have studied the chromatin structure and timing of DNA replication of the normal human beta-globin locus and a locus containing a de novo 25-kb deletion that removes elements of the LAR. As a result of this deletion, the entire beta-globin locus and sequences approximately 100 kb 5' and 3' of the adult beta-globin gene are DNase I-resistant and do not form characteristic distant hypersensitive sites. These sequences also replicate late in S phase in an erythroid cell background. In contrast, the sequences of the normal locus are DNase I sensitive and early replicating. These results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance. PMID- 2249770 TI - Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. AB - NF-E1, a DNA-binding protein that recognizes the general consensus motif WGATAR, is the first tissue-specific factor to be identified in erythroid cells. Using a probe from the murine GF-1 (NF-E1) cDNA clone, we isolated three homologous chicken cDNAs: One of these corresponds to an mRNA (NF-E1a) that is abundantly and exclusively expressed in erythroid cells; a second mRNA (NF-E1b) is also expressed in all developmental stages of erythroid cells but is additionally found in a limited subset of other chicken tissues; mRNA representative of a third gene (NF-E1c) is expressed only in definitive (adult) erythrocytes within the red cell lineage but is also abundantly expressed in T lymphocytes and brain. All NF-E1 proteins are highly conserved within the DNA-binding domain and bind to the consensus motif with similar affinities in vitro; they are also all stimulatory trans-acting factors in vivo. The factors differ quantitatively in their ability to trans-activate reporter genes in which the number and position of cognate binding sites is varied relative to the transcriptional initiation site. These data suggest that the NF-E1 consensus motif directs a broader and more complicated array of developmental transcriptional regulatory processes than has been assumed and that NF-E1c may play a unique regulatory role in the developing chicken brain and in T lymphocytes. PMID- 2249771 TI - The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system. AB - Generation of the anterior-posterior body pattern in the Drosophila embryo requires the activity of the segmentation genes. The segmentation gene runt has been classified as one of the primary pair-rule genes because of the pivotal role it plays in regulating the expression of other pair-rule genes. Here, we present the structure of this gene and describe the pattern of runt protein expression during embryogenesis. The deduced protein sequence shows no obvious overall homology with any sequences in the data base. The absence of an identifiable transcription factor motif (e.g., homeo box, zinc finger, leucine zipper, or helix-loop-helix) makes runt different from the other early-acting segmentation proteins. A runt-specific polyclonal antibody was generated and used to demonstrate that the subcellular location of the protein is in the nucleus. Double-staining immunolocalization experiments were used to determine the overlap of the runt protein pattern with the patterns of the pair-rule genes hairy (h), even-skipped (eve), and fushi tarazu (ftz). We found that the patterns of runt and hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary eve and ftz patterns. Experiments with the runt antibody also indicated that the protein is present throughout embryogenesis and is expressed extensively in the developing central and peripheral nervous system. PMID- 2249772 TI - The adenovirus major late transcription factor USF is a member of the helix-loop helix group of regulatory proteins and binds to DNA as a dimer. AB - We isolated full-length cDNAs encoding the 43-kD form of human upstream stimulatory factor (USF), a cellular factor required for efficient transcription of the adenovirus major late (AdML) promoter in vitro. Sequence analysis showed USF to be a member of the c-myc-related family of DNA-binding proteins. Using proteins translated in vitro, we identified a DNA-binding domain near the carboxyl terminus, which includes both a helix-loop-helix motif and a leucine repeat. We show that USF interacts with its target DNA as a dimer. The leucine repeat is required for efficient DNA binding of the intact protein and for interactions between full-length and truncated USF proteins. Interestingly, it is not required for DNA binding of the isolated helix-loop-helix domain. The structure of different cDNA clones indicates that USF RNA is differentially spliced, and alternative exon usage may regulate the levels of functional USF protein. PMID- 2249773 TI - Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. AB - The interaction of interferon-alpha (IFN-alpha) with a specific cell-surface receptor elicits physiological changes that rely on rapid transcriptional activation of a group of IFN-alpha-stimulated genes (ISGs). The IFN-stimulated response element (ISRE), a conserved regulatory element of all ISGs, is the target for transcriptional activation by the positive regulator IFN-stimulated gene factor-3 (ISGF3). We reported previously that post-translational activation of ISGF3 in the cytoplasm of IFN-alpha-treated cells requires two cytoplasmic activities (ISGF3 alpha and ISGF3 gamma) to produce an ISRE-binding complex that accumulates in the nucleus. In this study, we show that these activities are actually distinct subunits of the ISGF3 complex, which associate through noncovalent interaction. Sedimentation analysis, protein renaturation, and photoaffinity cross-linking of enriched preparations of cytoplasmic ISGF3 alpha and ISGF3 gamma and of nuclear ISGF3 demonstrated that ISGF3 gamma was a 48-kD polypeptide with intrinsic, low-affinity DNA-binding activity. Four polypeptides of 48, 84, 91, and 113 kD bound to the ISRE in vitro; the larger three polypeptides most likely compose the ISGF3 alpha component. These ISGF3 alpha polypeptides were unable to bind DNA alone but formed a DNA-binding complex in conjunction with ISGF3 gamma. The resulting heteromeric complex had the same ISRE binding specificity as the individual ISGF3 gamma polypeptide but approximately 25-fold higher affinity. Whereas ISGF3 gamma partitioned between the cytoplasm and nucleus in unstimulated cells, ISGF3 alpha was stimulated to translocate to the nucleus only following IFN-alpha treatment, resulting in preferential nuclear accumulation of both ISGF3 alpha and ISGF3 gamma as a stable ISGF3-ISRE complex. This regulated nuclear translocation of an activated transcription factor subunit maintained the specificity and rapidity of the IFN-alpha signaling pathway. PMID- 2249774 TI - Isolation of two developmentally regulated genes involved in spore wall maturation in Saccharomyces cerevisiae. AB - During sporulation of Saccharomyces cerevisiae, the four haploid nuclei generated by meiosis are encapsulated within multilayered spore walls. Taking advantage of the natural fluorescence imparted to yeast spores by the presence of a dityrosine containing macromolecule in the spore wall, we identified and cloned two genes, termed DIT1 and DIT2, which are required for spore wall maturation. Mutation of these genes has no effect on the efficiency of spore formation or spore viability. The mutant spores, however, fail to accumulate the spore wall-specific dityrosine and lack the outermost layer of the spore wall. The absence of this cross-linked surface layer reduces the resistance of the spores to lytic enzymes, to ether, and to elevated temperature. Expression of the DIT and DIT2 genes is restricted to sporulating cells, with the DIT1 transcripts accumulating at the time of prospore enclosure and just prior to the time of dityrosine biosynthesis. Both genes act in a spore-autonomous manner implying that at least some of the activities responsible for forming the outermost layer of the spore wall reside within the developing spore rather than in the surrounding ascal cytoplasm. As the DIT2 gene product has significant homology with cytochrome P-450s, DIT2 may be responsible for catalyzing the oxidation of tyrosine residues in the formation of dityrosine. PMID- 2249775 TI - Characterization of a cDNA encoding for the 28.5-kDa LHCII apoprotein from the unicellular marine chlorophyte, Dunaliella tertiolecta. AB - Three distinct clones, encoding light-harvesting chlorophyll (LHCII) proteins associated with photosystem II were isolated from a cDNA library of the unicellular marine chlorophyte, Dunaliella tertiolecta. We determined the nucleotide sequence of one of these clones, as well as the N-terminal amino acid (aa) sequences of the four mature LHCII apoproteins (24.5, 28.5, 30 and 31 kDa). The sequenced cDNA clone encoded the precursor of the 28.5-kDa apoprotein. We deduced that the transit peptide is 30 aa long and the mature protein is processed between A and V within the peptide RAAVEFYGP. Southern blots of D. tertiolecta genomic DNA indicated the presence of three to five genes. The algal aa sequence differs from higher plants mainly in the transit peptide and the N terminus. Several aa residues, highly conserved in higher plants, which are believed to play a role in chlorophyll binding, are not conserved in the chlorophytes. PMID- 2249776 TI - Selective enrichment of cDNAs from salt-stress-induced genes in the wheatgrass, Lophopyrum elongatum, by the formamide-phenol emulsion reassociation technique. AB - We present a novel technique for the enrichment of cDNA libraries to enhance the abundance of clones of differentially expressed genes. The technique is relatively simple, requires moderate quantities of poly(A) + RNA and results in preferential enrichment of clones derived from mRNAs that were of low abundance in their original population. This method was used to isolate cDNA clones of salt stress-induced genes in the roots of Lophopyrum elongatum, a highly salt-tolerant wheatgrass. An excess of sonicated plasmid DNA from a cDNA library from nonstressed roots was hybridized in a formamide-phenol emulsion with inserts from a cDNA library of stressed roots. Clones that were more abundant in, or were unique to, the library of the stressed roots were recovered as double-stranded fragments by virtue of reconstituted restriction-enzyme-digested ends by ligating them to a plasmid vector. The resulting enriched library was screened by differential colony hybridization and clones of eleven different genes that were more strongly expressed in stressed roots than in controls were selected. PMID- 2249777 TI - Genomic footprinting of proteins interacting with the chicken lysozyme promoter. AB - The functions of the promoter of the chicken-lysozyme-encoding gene (Lsz) are complex, since, on the one hand, the promoter serves to mediate the effects of five upstream regulatory elements and, on the other, it contains itself important regulatory sequences. To analyze this interplay we first monitored protein-DNA interactions at the Lsz promoter in hormonally regulated oviducts and in constitutively expressing HD11 cells by in vivo genomic footprinting. Two regions of strong protein-DNA interactions shared by both HD11 and oviduct cells were localized between nucleotides (nt) -105 and -119 and between nt -61 and -74, respectively. A third region of protein-DNA contacts was found selectively in HD11 cells from nt -199 to -204; this region corresponds in position with a previously identified HD11 cell-specific enhancer element. Furthermore, we determined the sites hypersensitive to an endogenous endonuclease in isolated nuclei using the genomic sequencing protocol. These sites fall into two regions: one encompasses the in vivo localized protein-DNA contacts between nt -105 and 119 and between nt -61 and -74; the other was found in a sequence largely devoid of in vivo protein-DNA interactions. We hypothesize that hypersensitive cleavage sites are generated by protein-induced changes in the DNA conformation. PMID- 2249778 TI - Structure of the mouse gene encoding parathyroid hormone-related peptide. AB - The parathyroid hormone-related peptide (PTHRP) was initially isolated from tumors associated with the syndrome of humoral hypercalcemia of malignancy. The human PTHRP gene is a complex transcriptional unit which uses multiple promoters and contains alternatively spliced 3' exons that result in mRNAs encoding three different deduced products. We report here the structure of the mouse PTHRP gene. The mouse gene has a considerably simpler organization than its human counterpart. This organization includes a single 3' exon and an apparent single 3' splicing pathway, leading to an mRNA encoding a 139-amino acid mature PTHRP. In addition, the mouse gene appears to be predominantly under the control of a short proximal promoter element. By RNase protection analysis, we identified PTHRP mRNA in specimens prepared from a variety of normal rodent tissues, including a number of tissues not previously recognized as sites of PTHRP gene expression. PMID- 2249779 TI - Structural analysis of the rabbit TNF locus, containing the genes encoding TNF beta (lymphotoxin) and TNF-alpha (tumor necrosis factor). AB - The genes coding for 20-kDa lymphotoxin (TNF-beta) and tumor necrosis factor (TNF alpha) have been cloned from a rabbit genomic library. The two genes are tandemly arranged and separated by only 1 kb of DNA, as previously observed in human and mouse genomes. We have sequenced the entire rabbit lymphotoxin-encoding gene and inferred the primary structure of rabbit TNF-beta, whose cDNA is not yet cloned. We also analysed the upstream sequences of the rabbit TNF-beta and TNF-alpha genes and identified a number of potential binding sites for known nuclear transcription factors, and in particular several putative kappa B-type sequences. PMID- 2249780 TI - Characterization of the Alu-rich 5'-flanking region of the human prothrombin encoding gene: identification of a positive cis-acting element that regulates liver-specific expression. AB - The nt sequence of 6127 bp of sequence upstream of the human prothrombin-encoding gene (F2) has been determined. Since we previously characterized 417 bp of DNA immediately upstream from the transcription start point (tsp), 6544 bp of continuous flanking sequence are known. Eleven Alu repeat sequences present in this region comprise 45% of the sequence; other repetitive sequences were identified by searching GenBank. The tsp was found to be heterogeneous by exon mapping and primer extension analysis. To localize the cis-acting sequences responsible for the liver-specific expression of F2, hybrid cat genes were constructed with various lengths of F2 5'-flanking region cloned upstream from a promoterless cat gene. After transfection into HepG2 and HeLa cells, it was inferred that the region between nt -1101 and -798 was required for synthesis in HepG2 cells; no synthesis was observed using these constructs in HeLa cells. Two sequences for known liver-specific or regulatory cis-acting sequences were identified in this region. PMID- 2249781 TI - A human integrin beta 1 subunit with a unique cytoplasmic domain generated by alternative mRNA processing. AB - The integrin subunit (beta 1) is common to a group of plasma membrane glycoprotein heterodimers that include the fibronectin, laminin and collagen receptors. These receptors span the plasma membrane, providing a transmembrane linkage between the extracellular matrix and the cytoskeleton. Here, we describe a variant of the human beta 1 differing from the previously described beta 1 in the cytoplasmic domain. The variant beta 1 transcript (beta 13'v) is present in different cell types and is synthesized at lower levels compared to the beta 1 mRNA. The cytoplasmic domain of the beta 13'v is characterized by a unique 12 amino acid C-terminal sequence. A Tyr residue present in this region, and known to be phosphorylated in the beta 1, is no longer part of a consensus sequence for phosphorylation by Tyr kinases. The integrin cytoplasmic domain anchors actin fibrils to the plasma membrane by interacting with cytoskeletal proteins such as talin and fibulin. The integrin beta 13'v with the variant cytoplasmic domain is likely to mediate a new type of membrane-cytoskeleton interaction during cell cell and cell-matrix adhesion. Analysis of genomic clones showed that the new sequences of the variant mRNA are identical to an intron located between the last two exons of the beta 1 gene, indicating that the alternative message is generated either by premature transcription termination or by lack of splicing at this site. PMID- 2249782 TI - Conditional expression of foreign genes by temperature-sensitive mutants of vaccinia virus. AB - To assess the utility of two temperature-sensitive (ts) mutant vaccinia viruses as vectors for the conditional in vitro expression of recombinant foreign genes, we have studied the kinetics of expression of foreign genes incorporated into these viruses. At nonpermissive temperature, 40 degrees C, these viruses were defective either in DNA synthesis or in virus assembly. Foreign gene expression was affected by the nature of the ts lesion and by the nature of the vaccinia promoter positioned upstream from the foreign gene. With both vector viruses, a foreign gene controlled by the p7.5 early-late promoter was expressed at both 33 degrees and 40 degrees C. With the DNA synthesis-defective vector virus, foreign gene expression controlled by the p11 DNA synthesis-dependent late promoter was inhibited at 40 degrees C, but could be turned on by shift to 33 degrees C. This ts expression system provides an alternative to use of drugs that inhibit DNA synthesis as a means for experimental manipulation of gene expression. Both vector viruses can be used with existing vaccinia virus expression technology. PMID- 2249783 TI - Promoter sequence and chromosomal organization of the genes encoding glycophorins A, B and E. AB - The promoter and exon 1 sequences of the genes encoding erythrocyte glycophorins GPA, GPB and GPE were investigated in detail, both from a genomic clone sorted out of a human leukocyte library and from genomic clones obtained by polymerase chain reaction amplification of total genomic DNA from control individuals and from GAP and/or GPB deletion variants. The three exons 1 and upstream sequences were shown to be highly homologous with only a few point mutations that did not affect the potential cis-acting elements (CACCC, NF-E1 and NF-E2) that are present in the same position within the three genes. Moreover, these genes share the same transcription start point. Analysis of the exon 1 and promoter sequences together with the gene defects occurring in the GP variants indicate that unequal cross-overs between the three genes are responsible for deletions and the generation of hybrid gene structures in which the promoter of one gene is brought close to another gene of the family. On the basis of these studies, a model of the gene organization is proposed to explain the rearrangements occurring in the variants. PMID- 2249784 TI - Two methods for rapid assembly and oligomerization of synthetic genes: construction of human calcitonin-encoding sequences. AB - Two fast, simple and reliable methods for construction of synthetic genes are described. The first represents a one-vial method for assembly and cloning of monomeric genes, and the second allows a simultaneous assembly, oligomerization and cloning of synthetic genes. Both methods consist of ligation of the synthetic oligodeoxyribonucleotides (oligos) building up the gene directly into the cloning vector, followed by screening of the recombinant clones for the presence of specific gene constructs. The average length of the oligomeric genes thus constructed is directly proportional to the molar ratio between the vector DNA and the synthetic oligos used. Both methods are illustrated by the construction of a series of human calcitonin-encoding genes. PMID- 2249785 TI - Nucleotide sequence of the gene encoding mouse transition protein 2. AB - The gene encoding the testis-specific basic chromosomal protein, mouse transition protein 2, is split by a single small intron that falls between the first and second nucleotides of a codon. Since the genes encoding protamines 1 and 2 and transition protein 1 in mammals contain a single intron in the same position, protamines and transition proteins appear to be evolutionarily related. PMID- 2249786 TI - Structure of a mouse histone-encoding gene cluster. AB - In addition to a previously described histone (H)-encoding H4 gene [Meier et al., Nucleic Acids Res. 17 (1989) 795], the mouse genomic DNA clone 53 contains two H3 genes, one functional and one partially deleted H2A gene, and one H2B gene. Clone 53 overlaps for 3 kb with MH143, another previously isolated mouse H-encoding clone [Yang et al., J. Biol. Chem. 262 (1987) 17118-17125], thus defining a 32-kb region of mouse chromosome 13 with a total of seven H-encoding genes. We have determined the nucleotide sequences and transcription start points of two genes coding for the H2A.1 and H3.2 proteins. PMID- 2249787 TI - Structures of four human pseudogenes for U7 small nuclear RNA. AB - Four U7 RNA-related sequences were isolated from a human genomic DNA library. None of the sequences completely match the published human U7 RNA sequence and all of them contain features typical of reverse-transcribed pseudogenes. PMID- 2249788 TI - Sequence of the putative LDL receptor binding regions of apolipoprotein B in mouse and hamster. PMID- 2249790 TI - Electrical excitability of skeletal muscle postmortem in casework. AB - The paper gives a review of the development of methods of postmortem electrical excitability of skeletal muscle for determining the time since death. For practical application in casework, the following method can be proposed: position of electrodes in the orbicularis oculi muscle, stimulation by rectangular impulses of 10 ms duration, 30 mA in a repetition rate of 50/s. The muscular reaction on excitation is graded in 6 degrees according to the spread of movement and the intensity of contraction. To each degree a time information is corresponding (95%-limits of confidence). These 95%-limits of confidence were proved to be valid for cases of sudden natural or traumatic deaths. EXCLUSIONS: deaths after chronic lingering disease (shorter times), fatal hypothermia, haematomas, emphysemas of the eyelid (longer times). The practical application in casework together with the temperature method (Henssge 1988, 1) is described. Applying both methods the death time estimation in the early postmortem interval may be much more precise and accurate than using one method alone. PMID- 2249789 TI - Aberrant radioimmunoassay results for cannabinoids in urine. AB - False negative and false positive radioimmunoassay results for cannabinoids in urine are reported. Such results occur infrequently and appear to be due to non specific binding of the radiolabel by interfering substances, possibly proteins, in the specimens. False negatives arise when these substances and the non specifically bound radiolabel are precipitated by polyethylene glycol in the separation stage of the assay, increasing the radioactivity in the bound fraction and thus lowering the assay result. False positives occur when the interfering substances and non-specifically bound radiolabel remain in solution during the separation stage, increasing the radioactivity in the free fraction and giving an erroneously high result. False positives could also occur in assays involving solid-phase antibodies or second-antibody separations. Methanol treatment of the samples prior to analysis precipitates the interfering substances and eliminates the aberrant effect. The interfering substances have not been identified through common serum proteins and semen have been excluded. No common factor in the circumstances of the cases that can account for the results has been identified. PMID- 2249791 TI - Hyperphosphatasia-osteoactasia detected during anthropological examination. AB - Minor N.Ny., a 2-year-old girl, was examined in 1986 in a contested paternity case by an order of court. The defendant did not admit paternity and named another man, so anthropological and blood-group examinations were performed on mother, child and the two men. Giving expert opinion may prove to be difficult following anthropological examinations for developmental anomalies of either party. However, the observed disease or developmental anomaly may have clinical importance for parties examined 'by chance'. In our case morphological deviation was detected in mother. PMID- 2249792 TI - A modified Gustafson method of age estimation from teeth. AB - Modifications to the Gustafson method of age estimation from teeth are described. They are designed to minimise the subjective nature of the scoring technique and to quantify the regressive changes in the enamel, dentine and cementum. Randomly selected teeth from 25 Indians were examined by the Gustafson method and by our own modification. It was shown that our modified method resulted in more accurate and reproducible age estimations than did the original method. PMID- 2249793 TI - Lewis typing of human saliva stains by enzyme-linked immunosorbent assay (ELISA) using monoclonal anti-Le(a) and anti-Le(b) antibodies. AB - The Lewis blood grouping of human saliva stains could be detected by an enzyme linked immunosorbent assay (ELISA) using anti-Le(a) and anti-Le(b) monoclonal antibodies with an avidin-biotin complex (ABC). The saliva stains (1.0 by 1.0 cm in size) were used as samples and not only could the Lewis substances of 57 individual stains be correctly typed by this method, but also it was clarified that there are several different secretion patterns of amounts of Le(a) and Le(b) substances in 3 individual Lewis types. PMID- 2249794 TI - The zinc test as an alternative for acid phosphatase spot tests in the primary identification of seminal traces. AB - The value of the acid phosphatase spot test in the primary visualization and identification of seminal traces is hampered by the sensitiveness of the enzyme to biodegradation. An alternative spot test is proposed, based on the high concentration of the more stable zinc metal in seminal plasma. The proposed zinc spot test is simple and suitable for on site investigation. Although the sensitivity in fresh stains is lower than that of the acid phosphatase spot test, this is largely compensated by the lower sensitiveness to biodegradation. The specificity for semen is higher than that of the acid phosphatase spot test. In vaginal swabs it was nevertheless seen, that samples should be taken within 24 h after alleged sexual assault to give reliable results. PMID- 2249796 TI - Necrotizing lymphadenitis: a review of clinicopathological, immunohistochemical and ultrastructural studies. AB - Necrotizing lymphadenitis (NEL) has been reported to be a reactive process described under differing terminology by Fujimoto et al. (1972), Kikuchi (1972), Wakasa et al. (1973) and other Japanese pathologists. Recently, this type of lymphadenitis has also been reported in America and Europe. In Japan, NEL is observed more frequently in the northern area, however, no characteristic seasonal occurrence has been noted. The disease affects young females more than males, particularly from the third and fourth decades onwards. Common cold-like symptoms, lymphadenopathy of the cervical region and leukopenia are characteristic clinical findings in the early stages. Morphological features of the involved lymph nodes include the presence of numerous immunoblasts, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Tubular inclusions are observed ultrastructurally. Immunohistochemical studies of peripheral blood using monoclonal antibodies have revealed that the helper/suppressor (Leu 3a/2a) ratio increases gradually with the clinical course because of a decrease in Leu 2a + cells. The pathogenesis of NEL is uncertain, but it has been speculated that there is cytolytic infection of lymphocytes by a virus or other organism, accompanied by secondary blastic transformation of suppressor T-lymphocytes. PMID- 2249797 TI - DSM-IV in progress. The multiaxial system. PMID- 2249795 TI - Characterization of giant cells in Hodgkin's lymphomas by immunohistochemistry applied to randomly collected diagnostic biopsies from the German Hodgkin Trial. AB - A panel of 10 monoclonal antibodies reactive with formalin-resistant epitopes was applied to characterize the giant cells of the Reed-Sternberg, Hodgkin, and lacunar cell types in diagnostic biopsies from the German Hodgkin Trial. The 94 tissue samples examined had been sent to the Reference Center by 44 different laboratories which made the initial diagnoses. A board of four referees re classified the primary diagnoses established by the 44 different histopathologists, providing subtyping of Nodular Sclerosis according to Bennett et al. (1985, 1989). Only cases with unequivocal agreement among the referees and which satisfied standards of fixation and embedding were included. Giant cells stained positively with: Ber-H2 in 92 per cent (81/88), LN-2 in 86.4 per cent (76/88), and DAKO-M1 in 72.2 per cent (64/88) of cases in which the lymphocyte predominance type was not included. Positive staining was quite rare with the other seven monoclonal antibodies. No significant difference in reactivity was revealed between giant cells of Reed-Sternberg, lacunar or Hodgkin cell types. Approximately one third of the cases were negative for at least one of the markers, Ber-H2, LN-2 or DAKO-M1. The lymphocytic and histiocytic cells in lymphocyte predominance Hodgkin's disease displayed a distinctive staining pattern with positivity for B-cell markers, whereas DAKO-M1 and Ber-H2 were predominantly negative. Finally, we found that randomly collected blocks of primary biopsies permit reliable immunostaining by this panel of monoclonal antibodies, since our results agree with results from the literature obtained from biopsies processed according to more uniform protocols for fixation and embedding. PMID- 2249798 TI - Group psychotherapy with older people. PMID- 2249799 TI - The Robert Wood Johnson Foundation Program on Chronic Mental Illness: an overview. AB - In 1985 the Robert Wood Johnson Foundation implemented the Program on Chronic Mental Illness, which provides grants and assistance to nine cities across the country in their efforts to improve services to persons with chronic mental illness. A basic premise of the program is that a central mental health authority is the cornerstone of improved systems of care. To be eligible for participation in the program, each city had to develop a service system incorporating a central authority and four other features: continuity of care, a full range of services, a housing plan, and new sources of financing. The authors describe how the cities were selected and how the program operates. They also provide a case example of the problems one city faced in establishing a central authority. PMID- 2249800 TI - Design for the national evaluation of the Robert Wood Johnson Foundation Program on Chronic Mental Illness. AB - The Robert Wood Johnson Foundation chose the University of Maryland Mental Health Policy Studies Program to conduct an independent national evaluation of its Program on Chronic Mental Illness, a large-scale demonstration in which nine cities across the country are participating. The national evaluation aims at describing the implementation of the program and assessing its impact on clients. The evaluation effort comprises five groups of interrelated studies: a site-level study, a community care study, housing studies, financing studies, and disability and vocational rehabilitation studies. Taken together, the components of the evaluation should provide evidence that will help create new structures and processes in large cities for delivering care to persons with chronic mental illness. PMID- 2249801 TI - Form and function of mental health authorities at Robert Wood Johnson Foundation Program sites: preliminary observations. AB - The Robert Wood Johnson Foundation Program on Chronic Mental Illness provides support for broad change in the organization, financing, and delivery of services in public systems of care for chronic mentally ill persons. To address the lack of an organizational locus of responsibility in these systems, the foundation proposed that each of the nine cities participating in the program create a mental health authority that would centralize administrative, clinical, and fiscal oversight. The authors present site-by-site observations of the developing mental health authorities at the end of the program's two-and-a-half-year planning phase. They conclude that although the Robert Wood Johnson Foundation grant represented a significant incentive for innovation, at this relatively early stage in the demonstration authorities at only a few sites had achieved direct clinical responsibility for chronic mentally ill persons. Although services had expanded, no site had yet developed a comprehensive system of care that included inpatient services as well as a full range of ambulatory, housing, and social welfare services. PMID- 2249802 TI - A pilot assessment at one month of 17 dual diagnosis patients. AB - A pilot one-month follow-up of 17 inpatients diagnosed with both psychiatric and substance abuse disorders showed that 12 patients reported abstinence and five had relapsed. Significant associations were found between reported abstinence and a diagnosis of a depressive disorder, high motivation for abstinence, and the patient's perception that a specific discharge plan for substance abuse treatment had been developed. PMID- 2249803 TI - Psychotic denial of pregnancy: phenomenology and clinical management. AB - Psychotic denial of pregnancy in chronic mentally ill women may place the women and their fetuses at high risk of postpartum emotional disturbance, precipitous or unassisted delivery, fetal abuse, and neonaticide. Psychotic denial of pregnancy is illustrated with case reports from an inpatient program for pregnant mentally ill women. Women who denied their pregnancies tended to have a diagnosis of chronic schizophrenia, to have previously lost custody of children, and to anticipate separation from the baby they were carrying. The author suggests that treatment for such patients should take place in a setting that integrates comprehensive psychiatric and obstetrical care and may include pharmacotherapy, supportive psychotherapy, and evaluation of the patient's parenting skills and support network to assess whether she is able to keep her baby. PMID- 2249804 TI - The use of ultimatums in psychiatric care. AB - One way in which psychiatrists deal with the problem of a patient who does not follow treatment recommendations is to issue an ultimatum, refusing treatment unless the patient abides by the doctor's treatment plan. The author examines a series of cases to outline seven general principles that can help the psychiatrist decide whether to use an ultimatum and to help make its use a thoughtful clinical intervention rather than an expression of exasperation. The guidelines address practical considerations, such as the complicating fact that ultimatums limit the psychiatrist's future responses to the patient, and ethical issues, such as the possible intrusion of the psychiatrist's self-interest or institutional pressures into treatment ultimatums. PMID- 2249805 TI - Characteristics of sheltered care facility operators in California in 1973 and 1985. AB - During the past 20 years, sheltered care homes have become the primary supervised community residence for mentally ill patients outside of licensed hospitals. To determine factors associated with sheltered care operators' remaining in business, follow-up interviews were conducted in 1985 with operators of 151 sheltered care facilities in California whose operators had been surveyed in 1973. Fifty-five of the original operators continued to operate the facility at 12-year follow-up, and 96 were new to the facilities since 1973. Compared with the original operators, the new operators were younger and better educated, were more likely to be men, and were more likely to be totally dependent on the business for their income. Operators who were members of local associations for sheltered care operators were more likely to have remained in business over the 12-year period, as were those who owned facilities with more than six beds. PMID- 2249806 TI - Social skills training for acute psychiatric inpatients. PMID- 2249807 TI - Cocaine and polysubstance abuse by psychiatric inpatients. PMID- 2249808 TI - Self-reported HIV-related risk behaviors in acute psychiatric inpatients: a pilot study. PMID- 2249809 TI - Lorazepam in the treatment of acute conversion disorder. PMID- 2249810 TI - Financial barriers to care. PMID- 2249811 TI - The Madison model. PMID- 2249812 TI - Patient-therapist sex. PMID- 2249813 TI - Knowledge about AIDS. PMID- 2249814 TI - A forgotten antipsychotic. PMID- 2249815 TI - Data watch. Some hospitals cutting beds and services. PMID- 2249816 TI - Outpatient planning: still more art than science? AB - A general lack of comprehensive data on ambulatory care isn't preventing hospitals from engaging in high-quality planning in that area. "A good forecast" for future ambulatory care demand depends mainly on a "thoughtful determination of what needs to be forecasted and why," says Andrew McCulloch, chief operating officer at Harborview Medical Center, Seattle. The rapid pace of outpatient development has led some hospitals to invest a great deal of time and money to develop improved information systems. Those hospitals are heeding the statistical trends: Outpatient revenue grew far faster than inpatient did in 1990. PMID- 2249817 TI - Fund-raising strategies in hard times: what works for hospitals. AB - "It's been tough going" for fund-raising since the economy began its downturn earlier this year, says John Good, vice-president for community relations and development at Beverly (MA) Hospital. Like many hospitals, his institution has been hit hard by declining corporate contributions. Fortunately, individuals have stepped in to pick up the slack for Beverly. But hospitals are competing with a host of other worthy causes for philanthropic dollars. PMID- 2249818 TI - Employee grievance policy: don't discourage complaints. AB - Developing a grievance policy may not seem like an urgent agenda item for some hospital executives. But labor relations experts urge hospitals to establish strong employee grievance policies and make use of them. PMID- 2249819 TI - The top 10 developments in U.S. health care, 1990. PMID- 2249820 TI - Year in review. Letters to the editor: the public speaks up about... AB - The opinion pages of national newspapers reflected consumers' attitudes about hospitals and health care in 1990. Some of the following letters tell of the confusion and anger consumers feel when the nation's health care crisis has a personal impact on their families or friends. They also point out the importance of educating the public about the crisis and the pressures it puts on hospitals. PMID- 2249821 TI - Fax poll. 1990 was tough; few expect relief in '91. PMID- 2249822 TI - A year of strong opinions and soul-searching. PMID- 2249823 TI - Judge holds state Medicaid officials personally liable. PMID- 2249824 TI - Punitive-damage awards create hospital problems. PMID- 2249825 TI - Drug spending up, inventories down, 1990 survey shows. PMID- 2249827 TI - AHA enhances its Monitrend II data and services. PMID- 2249826 TI - New radiology standards reflect trouble spots. PMID- 2249828 TI - Don't rest when you come to a career plateau. PMID- 2249829 TI - Cleveland's experiment in measuring quality. PMID- 2249830 TI - Diversity of malignant melanoma and its precursor lesions. PMID- 2249831 TI - Malignant melanoma in situ. PMID- 2249832 TI - Malignant melanoma in situ. AB - There is general agreement that there are lesions which should be diagnosed as malignant melanoma in situ. The biologic behavior of the intraepidermal component of superficial spreading melanoma (the radial growth phase) has been demonstrated to have significantly different properties than those of the cells in the vertical growth phase. The central controversies regarding malignant melanoma in situ relate to the criteria for diagnosing melanoma and whether there are atypical melanocytic lesions which are neither nevi nor melanoma. I propose that reliable and reproducible objective criteria for melanoma have not been developed; rather, dermatopathologists use differing subjective criteria which result in diagnostic agreement in the vast majority of lesions. The controversy is over those lesions which are classified as melanoma by one set of criteria and not by others. I am also a proponent of the diagnosis of atypical melanocytic lesions, and have suggested an analogy to keratinocytic lesions in which this concept is well established. Studies of the sensitivity and specificity of the correlation between clinical and histologic features and the biologic behavior of melanocytic lesions are necessary to resolve these issues. PMID- 2249833 TI - Minimal deviation melanoma. PMID- 2249834 TI - Respiratory tract pathology in patients with severe burns. AB - The histologic spectrum, pathogenesis, and clinical correlates of tracheobronchial and pulmonary lesions were studied by autopsy in six children and 27 adult burn victims. The burns covered a mean total body surface area of 57.7 +/- 23%. The mean survival time was 17.6 +/- 14.3 days. Patients over 60 years tended to survive longer than younger adults, but older patients had less extensive burns (P less than .01). Moderate or severe renal failure was an important clinical complication in 19 patients (58%). Diffuse alveolar damage (DAD) was observed in 16 patients, acute bronchopneumonia in seven patients, and necrotizing pneumonia in seven patients. Both DAD and pneumonia coexisted in 11 patients. Children most consistently developed pneumonia, 6 out of 6 versus 4 out of 17 younger adults (P less than .05). Factors which may have contributed to the pathogenesis of DAD included septicemia (12 patients), hypotension (nine patients), necrotizing pneumonia (six patients), and oxygen toxicity (four patients), in addition to the common presence of inhalational injury. The onset of DAD appeared late in eight patients with long survival periods, suggesting causal factors other than inhalational injury. However, survival rate did not differ in patients with or without DAD, and there was no correlation between DAD and the extent of burns. Airway lesions reflected the length of survival and showed the following sequence of changes: (1) mucosal necrosis and denudation, (2) acute inflammation and ulceration, and (3) squamous metaplasia. Endotracheal intubation injury and superinfection were confounding factors beyond the first few days of survival. PMID- 2249836 TI - Ultrastructural heterogeneity of lung carcinomas: representativity of samples for electron microscopy in tumor classification. AB - Histologic heterogeneity of tumors is a well-known phenomenon, which has been repeated studied at the light microscopic level. Electron microscopy has been advocated as an adjunct in classification of tumors which pose difficulties on light microscopic classification. However, in view of tumor heterogeneity, it might be anticipated that the problem of sample error could detract from the usefulness of electron microscopy in tumor typing. Ultrastructural heterogeneity of tumors has thus far not been systematically investigated. We performed an ultrastructural randomized and blinded study of superficial and deep samples of 44 resected lung carcinomas, tumors which are notorious for their histologic heterogeneity. Neuroendocrine and squamous differentiation, as well as adenodifferentiation, were assessed separately and semiquantitatively in each sample. Twenty-six tumors showed more than one type of differentiation in at least one sample. However, in only two cases did the main type of differentiation differ between the two samples. A further nine cases showed one predominant differentiation type in both samples, but a similarly pronounced second differentiation type in one of the samples. Thus, in terms of ultrastructural diagnosis, the two samples showed a major discrepancy in two of 44 cases, and a minor discrepancy in nine of 44 cases. We conclude that ultrastructural heterogeneity of lung tumors is a common occurrence, but that it only rarely leads to totally different ultrastructural diagnoses. PMID- 2249835 TI - Early senile plaques in Alzheimer's disease demonstrated by histochemistry, immunocytochemistry, and electron microscopy. AB - To clarify early pathologic changes in Alzheimer's disease, the brains from two cases from a single family with this disease were examined. A mother who died at age 75 with severe dementia showed an abundance of typical senile plaques, neurofibrillary tangles, and cerebrovascular amyloidosis. The senile plaque and cerebrovascular amyloid were strongly immunoreactive to anti-beta protein antibody. Her son manifested erratic and bizarre behavior, and was suspected of having committed suicide at age 52. His brain weight and macroscopic observations were normal; however, Bielschowsky's silver impregnation and methenamine silver stains showed numerous argyrophilic plaque-like lesions in the neocortex. They were weakly immunolabeled by anti-beta protein antibody, but lacked any abnormal neurites of Congophilic amyloid deposits. These lesions resembled the "type 3" immunoreactive lesions (previously reported by us in Alzheimer's disease and Down's syndrome) which seem to be an early stage of senile plaque formation. These putative early plaque lesions were also examined by methenamine silver electron microscopy, and were seen to consist of loose aggregations of irregular spindle-shaped structures with a heavy deposition of silver grains, with genuine amyloid fibrils not being apparent. It is believed that the accumulation of beta protein immunoreactive material without amyloid fibril formation might be an initial step in the development of the senile plaque, and that the son, having extensive cortical involvement with type 3 plaque lesions, demonstrated clinical manifestations of less completely developed Alzheimer's disease. PMID- 2249837 TI - Structure of mucosa in continent ileal reservoirs 15 to 19 years after construction. AB - Mucosa biopsy specimens were obtained from 12 patients with continent ileostomy reservoirs constructed 15 to 19 years previously. Biopsies from normal ileal mucosa, taken from six other patients with no apparent bowel disease, served as controls. The specimens were processed for light and electron microscopy. The reservoir mucosae showed an increased amount of inflammatory cells, but there were no signs of dysplasia. In the goblet cells, sialomucins dominated over sulfomucins; in this respect no difference was found between reservoirs and controls. Morphometric studies showed an increase of mucus-storing goblet cells in the reservoir mucosae, both with regard to relative number and to volume density. The mitotic index was higher than normal in the reservoirs, but the relative number of the Paneth cells and the height of the villus epithelial cells were similar in the reservoirs and the controls. In the reservoirs, the surface amplification factors due to villi and to microvilli (near the villus tips) were reduced by some 29% and 20%, respectively, indicating villus hypotrophy. It is concluded that only minor morphologic changes appear in the ileal reservoir mucosa 15 to 19 years after construction. Morphometry provides a sensitive tool to demonstrate such changes in intestinal morphology. PMID- 2249838 TI - Role of elastic fiber degradation in emphysema-like lesions of pulmonary lymphangiomyomatosis. AB - To study the pulmonary structural remodeling in pulmonary lymphangiomyomatosis, electron microscopy and light and electron microscopic immunohistochemical observations for elastin and alpha 1-antitrypsin were performed on five open lung biopsy samples. Lung specimens showed emphysema-like changes in areas of abnormally accumulated smooth muscle cells. In the alveolar walls having accumulated smooth muscle cells, elastic fibers were decreased in number, disrupted, granular, and occasionally accumulated. Ultrastructurally, elastic fibers in areas of smooth muscle cell accumulation showed poorly outlined amorphous components and a few microfibrils, and occasionally showed electron dense granular deposits in and around the amorphous components. Spiraling collagen fibrils were frequently found associated with these abnormal elastic fibers. Immunohistochemistry for elastin showed even staining of amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. alpha 1-Antitrypsin was also detected evenly in amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. It is proposed that the emphysema-like lesions of lymphangiomyomatosis are mediated by the degradation of elastic fibers, and these degraded elastic fibers are related to an imbalance of the elastase/alpha 1-antitrypsin system similar to the probable pathogenesis of emphysema. PMID- 2249839 TI - Primary large-cell lymphoma of the thymus: a diffuse B-cell neoplasm presenting as primary mediastinal lymphoma. AB - Primary mediastinal nonlymphoblastic non-Hodgkin's lymphoma (NLNHL) has distinct clinical, histologic (diffuse large-cell morphology, often with sclerosis and clear cytoplasm), and immunohistochemical features (predominantly B-cell lineage, usually immunoglobulin-negative), which suggest origin from a unique B-cell population. The thymus has a resident population of B cells with a unique immunophenotype, and can be involved by primary mediastinal NLNHL, in some cases selectively. Fifteen cases of NLNHL involving the thymus were studied by paraffin section immunohistochemistry using antibodies to formalin-resistant epitopes of B cells (4KB5 [CD45RA] and L26 [CD20]) and T cells (L60 [CD43] and UCHL1 [CD45RO]). All were diffuse large-cell or immunoblastic lymphomas with sclerosis, and were also similar to primary mediastinal NLNHL in clinical features. Neoplastic cells stained with L26 in all but one case, which stained with 4KB5 and an antibody to a leukocyte-common antigen (PD7/26 [CD45RB]), and were uniformly nonreactive with L60 (with one exception) and UCHL1. Intermingled small lymphocytes were uniformly L26-negative and positive for T-cell markers, even in one case with atypia suggesting a lymphoma of mixed morphology. These findings demonstrate that primary thymic and primary mediastinal NLNHL are similar B-lineage neoplasms, and support previous suggestions that both may originate in thymic B cells. PMID- 2249840 TI - HLA-DR expression in B-cell non-Hodgkin's malignant lymphomas: a multiparameter flow cytometry study. AB - Ten cases of reactive follicular hyperplasia and 31 cases of B-cell non-Hodgkin's malignant lymphoma were studied using multiparameter flow cytometry. A bimodal distribution for HLA-DR expression, but not for surface immunoglobulin or B cell specific antigens CD19 and CD20, was observed commonly in mixed cell type and infrequently in non-mixed cell type B-cell malignant lymphomas. On the basis of HLA-DR distribution alone, 31 cases of B-cell malignant lymphomas of low, intermediate, and high grades could be separated into mixed and non-mixed cell types, with only two misclassifications (P = 0.0001). Exceptionally, one case of malignant lymphoma, follicular and diffuse, mixed-cell type had a unimodal HLA-DR distribution, and one case of malignant lymphoma, diffuse, large noncleaved cell type had a bimodal HLA-DR distribution. In all cases of malignant lymphoma, follicular, mixed-cell type studied, low HLA-DR was correlated with small cells, and high HLA-DR was correlated with large cells. In contrast, HLA-DR expression and cell size were not as directly correlated in cases of malignant lymphoma, diffuse, mixed-cell type. These observations suggest that most, but not all, cases of B-cell malignant lymphomas of the mixed cell type can be separated from other B-cell lymphomas on the basis of HLA-DR distribution. PMID- 2249842 TI - Tubo-ovarian abscess caused by Streptococcus pneumoniae. AB - A 46-year-old black woman underwent exploratory surgery for evaluation of a tender mass in her abdomen. During the exploratory surgery bilateral tubo-ovarian abscesses ruptured. Specimens from both tubes and from the wall of the abscesses contained bacteria seen on the Brown-Hopps tissue gram stain. The bacteria were gram-positive, lancet-shaped diplococci characteristic of Streptococcus pneumoniae. Immunoperoxidase stains confirmed the identification of the organism as S pneumoniae. PMID- 2249841 TI - Genomic analysis of T-cell receptor and immunoglobulin antigen receptor genes and breakpoint cluster regions in gastrointestinal lymphomas. AB - Sixteen cases of gastrointestinal B- and T-cell lymphoma were investigated for clonal rearrangements of immunoglobulin and T-cell receptor genes. In all cases the immunogenotype data corresponded well with the immunohistochemical findings, thus confirming the biologic heterogeneity of these lymphomas. Some cases could be distinguished by additional heterogeneity in their genotype which could not be detected by immunohistochemical methods. Moreover, the B-cell lymphomas were studied for the presence of the chromosomal translocations t(11;14) and t(14;18) using probes for bcl-1 and bcl-2 genes, respectively. While bcl-1 rearrangement was not present in these gastrointestinal lymphomas, one case of diffuse low grade lymphoma of mucosa-associated lymphoid tissue and three cases of centroblastic lymphoma (diffuse large cell) could be shown to have detectable bcl 2 rearrangement. PMID- 2249843 TI - Cerebral amyloid angiopathy and granulomatous angiitis: immunohistochemical study using antibodies to the Alzheimer A4 peptide. AB - Neuropathologic study of an 82-year-old male who died from massive cerebral hemorrhage showed extensive amyloid angiopathy, with morphologic and immunohistochemical characteristics similar to those observed in Alzheimer's disease, associated with granulomatous angiitis, including the presence of numerous giant cells. Some of the giant cells contained, in their cytoplasm, congophilic material immunoreactive for the Alzheimer A4 peptide, supporting the hypothesis that the granulomatous angiitis may, in part, represent a foreign body reaction to A4 amyloid deposition. PMID- 2249844 TI - The complete sequence of the human beta-myosin heavy chain gene and a comparative analysis of its product. AB - We have isolated and sequenced the gene and the cDNA coding for the human cardiac beta-myosin heavy chain (designated MYH7). The gene is 22,883 bp long. The 1935 amino acids of this protein (Mr223,111) are encoded by 38 exons. The 5' untranslated region (86 bp) is split by two introns. The 3' untranslated region is 114 bp long. Three Alu repeats were identified within the gene and a fourth one in the 3' flanking intergenic region. The molecular organization of this gene reflects the conservative pattern with respect to size, coding ratio, and number or position of introns characteristic of vertebrate sarcomeric myosin heavy chain genes. The protein sequence of the human beta-heavy chain was compared with corresponding (homologous) sequences of rabbit, rat, and hamster as well as with the (heterologous) embryonic heavy chain sequences of rat, chicken, and man. The results show that protein subregions responsible for basic functions of myosin heavy chains (nucleotide binding and actin binding) are very similar in homologous and heterologous heavy chains. Regions that differ in their primary sequences in heterologous heavy chains appear to be highly conserved within mammalian beta-myosin heavy chains. Constant and variable subregions of heavy chains are discussed in terms of functional significance and evolutionary relatedness. PMID- 2249845 TI - Giant G+C% mosaic structures of the human genome found by arrangement of GenBank human DNA sequences according to genetic positions. AB - To determine the overall variation in the G+C% distribution over long ranges of the human genome, DNA sequences of human genes, which were closely linked genetically or physically, were surveyed from the GenBank Data Bank. A total of 72 sequences longer than 2 kb, which were mutually linked within 500 kb, were identified. The sequences belonged to 17 linkage groups and were ordered in each group according to their genetic positions. Analyses of the G+C% distribution along the ordered sequences showed that sequences within each group almost always had similar G+C% levels, but those belonging to different groups often had different levels. Similar analyses of more distantly linked sequences (e.g., greater than 10 Mb) showed mosaic structures of G+C% distribution. These findings are consistent with predictions made from the "isochore" structures found by CsCl equilibrium centrifugation, in that the structures having homogeneous base compositions stretched over at least several hundred kilobases. A possible boundary of the giant G+C% mosaic structures was identified between X-linked G6PD and F8C. PMID- 2249846 TI - A testis-specific form of the human pyruvate dehydrogenase E1 alpha subunit is coded for by an intronless gene on chromosome 4. AB - The pyruvate dehydrogenase (PDH) complex converts pyruvate to acetyl CoA, an essential step in aerobic glucose metabolism. We have previously shown that the gene for the E1 alpha subunit of this complex, expressed in somatic tissues, is located on band p22.1 of the human X chromosome. This gene, PDHA1, contains 10 introns and spans approximately 17 kb. An autosomal locus, PDHA2, showing significant cross-hybridization with a PDH E1 alpha cDNA probe, was detected on chromosome 4, in the region q22-q23. We here report the isolation of human testis specific PDH E1 alpha cDNA clones. The similarity with the X chromosome-linked cDNA coding sequence at the nucleotide level is 84%. Specific amplification using the polymerase chain reaction confirmed the presence of a testis-specific mRNA and indicated that postmeiotic spermatogenic cells express this subunit. In situ hybridization with a unique probe from the 3' untranslated region of the testis specific cDNA showed that the gene for this form of PDH E1 alpha is localized on chromosome 4 in the region q22-q23. The autosomal human gene was isolated from a chromosome 4-specific genomic library. The transcribed region of this gene is identical to the testis-specific cDNA sequence. It completely lacks introns and possesses characteristics of a functional processed gene. PMID- 2249847 TI - Assignment of the human thyroid stimulating hormone receptor (TSHR) gene to chromosome 14q31. AB - In situ hybridization experiments on human chromosomes were performed using probes corresponding to the 5' and 3' parts of human TSHR cDNA. Both probes allowed a regional localization on chromosome 14q31. PMID- 2249848 TI - Two distinct mutations at the same site in the PCCB gene in propionic acidemia. AB - Propionic acidemia is an inborn error of metabolism resulting from a deficiency of propionyl-CoA carboxylase activity. The alpha- and beta-subunits of the enzyme are encoded by the PCCA and PCCB genes, respectively. Using direct sequencing and restriction digests of amplified reverse transcripts and genomic DNA, we have identified two mutations of the PCCB gene in a propionic acidemia patient from the pccC complementation subgroup (the PCCB gene contains the major complementation group pccBC and subgroups pccB and pccC). One of the proband alleles contains an inframe 3-bp deletion inherited from the father which results in the deletion of an isoleucine residue in the beta-subunit of the enzyme. The other mutant allele, inherited from the mother, has a 14-bp deletion and an addition of 12 bp of new sequence at the same site as the father's allele. The inserted sequence is a partial duplication of a sequence just upstream of the mutation site. The net result of this mutation generates a frameshift and a downstream stop codon. Examination of fibroblast mRNA from the patient showed that it consists essentially of the father's sequence, making it effectively the only expressed allele for the beta-protein. A survey of additional patient cell lines revealed the insertion/deletion rearrangement in three additional patients, two from the pccBC group and one unclassified. The 3-bp deletion allele was unique to the proband. The identification of two distinct alleles occurring at the same site in the PCCB gene underscores the importance of this site in enzyme function or integrity. PMID- 2249849 TI - Two families of low-copy-number repeats are interspersed on Xp22.3: implications for the high frequency of deletions in this region. AB - The locations of two families of low-copy-number repeats (CRI-S232 and G1.3) in the physical and genetic maps of the distal short arm of the human X chromosome (Xp22.3) have been determined. Single-copy fragments flanking several repeat elements from each family have been cloned and assigned to specific intervals on a deletion map of Xp22.3. Physical distances between these loci and previously isolated Xp22.3 markers have been determined by pulsed-field gel electrophoresis (PFGE). The positions of some of these markers on the genetic map of the region have been established by segregation analysis in CEPH families. Four members of the CRI-S232 family have been localized within 3 Mb on Xp22.3, interspersed with two members of the G1.3 family. Both deletion and PFGE mapping data suggest that a CpG island localized in a specific position on the map might be associated with the Kallmann syndrome gene. Unlike the previously reported data on hyperpolymorphic minisatellite sequences, no increase in the recombination rate was detected around the CRI-S233 repeats. The presence of several repeat elements in a region with a very high frequency of deletions, such as Xp22.3, is highly suggestive of the occurrence of unequal crossovers between the various elements, leading to deletion events. PMID- 2249850 TI - Second-generation approach to the construction of yeast artificial-chromosome libraries. AB - We describe an improved method for construction of yeast artificial-chromosome (YAC) libraries that contain large inserts of foreign DNA. The procedure consists of seven steps: (i) preparation of human DNA in agarose beads; (ii) partial digestion of the DNA with EcoRI; (iii) electrophoretic elimination of the smaller partial-digest fragments; (iv) ligation of the EcoRI fragments with vector arms in molten agarose; (v) hydrolysis of agarose with agarase; (vi) fractionation of the recombinant molecules by sucrose-gradient centrifugation; and (vii) transformation of yeast. More than 7000 colonies were obtained starting with 15 micrograms of human DNA, which was fractionated on a single sucrose gradient. The average size of these YACs was approximately 380 kb. It is estimated that the total length of human DNA present in the clones corresponds to 80% of the length of the human haploid genome. The results of screening the clones for a number of single-copy genes indicate that the clones reflect a nearly random sampling of the human genome. The efficiency of the cloning is sufficient to support the construction of multihit libraries for the human genome or for the genomes of other higher organisms. PMID- 2249851 TI - Nucleotide sequence of the gene for human transition protein 1 and its chromosomal localization on chromosome 2. AB - Transition protein 1 (TNP1) is a highly basic nuclear protein of 54 amino acids that is found in haploid spermatogenic cells during the period of transition of histones to protamines. Using the cDNA clone for human TNP1, we have isolated the gene encoding human TNP1 from human genomic libraries. The gene contains an intron of 200 bp; 1104 bp of the 5'- and 276 bp of the 3'-noncoding region have been sequenced. Comparison with the rat TNP1 gene yielded a similarity of 77% over the region between the transcription start point and the polyadenylation signal. The gene contains typical CAAT and TATAA boxes at conventional distances from the transcriptional start site. Using a series of human-rodent somatic cell hybrids containing variant complements of human chromosomes, the TNP1 gene was found to cosegregate with human chromosome 2. By in situ hybridization, the gene was assigned to the q35 and q36 bands of the long arm of chromosome 2. This chromosomal region encodes several genes, including TNP1, that are located on murine chromosome 1. PMID- 2249852 TI - Genomic analysis of a mouse zinc finger gene, Zfp-35, that is up-regulated during spermatogenesis. AB - Zinc finger genes are a class of eukaryotic regulatory genes that encode sequence specific nucleic acid-binding proteins. Members of this large gene family are required for growth and development in a wide range of organisms. We previously identified a mouse zinc finger gene, Zfp-35, that was up-regulated during spermatogenesis at the pachytene spermatocyte stage of development. We now describe the genomic organization of this gene, including its intron-exon structure, the sequence of its flanking regions, and its assignment to a region encompassing bands B3 to C of chromosome 18. The transcription unit has three exons. Intron 1 is within the 5' untranslated region and exon 3 contains the block of all 18 zinc fingers. These two features are common to a number of zinc finger genes. We also show that Zfp-35 is conserved in some placental mammals and that it is a member of a subfamily of related mammalian zinc finger genes. PMID- 2249853 TI - Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization. AB - A new strategy for analyzing chromosomal evolution in primates is presented using chromosomal in situ suppression (CISS) hybridization. Biotin-labeled DNA libraries from flow-sorted human chromosomes are hybridized to chromosome preparations of catarrhines, platyrrhines, and prosimians. By this approach rearrangements of chromosomes that occurred during hominoid evolution are visualized directly at the level of DNA sequences, even in primate species with pronounced chromosomal shuffles. PMID- 2249854 TI - Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid lipofuscinosis) gene (CLN3) maps to human chromosome 16. AB - The ceroid-lipofuscinoses are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. The underlying biochemical defect is unknown. Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) displays autosomal recessive inheritance. Genetic linkage studies were undertaken to determine the chromosomal location of the Batten disease mutation (CLN3). Following identification of linkage to the haptoglobin locus, linkage analysis has been carried out in 42 families by using DNA markers for loci on the long arm of human chromosome 16. The maximal lod score between Batten disease and the locus D16S148 calculated for combined sexes is 6.05 at a recombination fraction theta = 0.00. Multilocus analysis using five loci indicated the most likely order to be HP-D16S151-D16S150-CLN3-D16S148-D16S147. The maximal location score for CLN3 was 48 (equivalent to a lod score of 10.4) in that interval within this fixed marker map. PMID- 2249855 TI - Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses. AB - Infantile neuronal ceroid-lipofuscinosis (CLN1) is the form of neuronal ceroid lipofuscinoses (NCL) with the earliest onset of symptoms. The locus of the most common form of these disorders, juvenile NCL (CLN3), has been mapped to chromosome 16. We report here linkage data of the same region in Finnish CLN1 families. Our results indicate that CLN1 is not allelic with CLN3 but represents a different locus, which is not located within about 70 cM in chromosome 16. PMID- 2249856 TI - The bovine genome contains polymorphic microsatellites. AB - Dinucleotide repeats constitute so-called microsatellites of the human and other eukaryotic genomes. Microsatellite polymorphisms can be identified through the amplification of the microsatellite DNA using the polymerase chain reaction (PCR), followed by resolution of the amplified DNA fragments on a polyacrylamide sequencing gel. We performed a preliminary sequence database search to identify bovine sequences containing (CA)n, (AC)n, (GT)n, or (TG)n blocks, with n greater than or equal to 6. This search yielded 10 sequences containing one or two of the specified repeat blocks and often additional dinucleotide repeat blocks. One of the microsatellite-containing regions has been sequenced twice from independent clones and the reported sequences showed variation in the number of repeats. PCR amplified fragments of another sequence, the gene for steroid 21-hydroxylase, ranged from 186 to 216 nucleotides in 43 unrelated animals. The database search, as well as the hypervariable microsatellite in the bovine steroid 21-hydroxylase gene, indicates that dinucleotide blocks may be an abundant source of DNA polymorphism in cattle. PMID- 2249857 TI - Mapping of the gene for CNBP, a finger protein, to human chromosome 3q13.3-q24. PMID- 2249858 TI - Speech recognition in analog multichannel cochlear prostheses: initial experiments in controlling classifications. AB - Computer-synthesized vowels were used to examine methods for controlling and measuring the perceptions elicited during electrical stimulation of the human cochlea. In the first experiment, we measured the importance of the second formant (F2) in the identification of vowels, matched for duration, in a single subject with a multichannel cochlear implant. The subject never confused vowels having a "low" frequency F2 with those having a "high" frequency F2. In the second experiment, identification functions were generated for a series of vowels varying only in F2. When the pattern of F2 stimulation at the basilar membrane was manipulated, vowel identification functions were altered. For the categorization of vowels, the data indicate that the relative cochlear position of F2 stimulation was more important than fine-grain temporal waveform cues. The data are supportive of cochlear implant coding strategies that make use of cochlear place information. In the later experiments, we manipulated filter passbands and channel gains to explore their effect on these classifications. These preliminary studies indicate that it is possible to "fine-tune" such classifications. PMID- 2249859 TI - Dynamic interactions between accommodation and convergence. AB - Frequency-domain equations were derived for the current dual-interaction model of accommodation and convergence control, and its adaptive behavior was related to the system's parameters. Contrary to predictions based on the steady-state performance of the model [18], dynamic analysis showed that the AC/A is sensitive to the method of measurement and a procedure is established for its reliable determination. Additionally, the results provided theoretical support for the empirical finding that low AC/A and CA/C ratios are associated with high accommodative and convergence adaptation, respectively [15]. The derived equations should help future studies relate the physiological behavior of accommodative and convergence to specific model parameters. PMID- 2249860 TI - A stress wave propagation technique for bone repair study. AB - The diagnosis of bone fracture and its rate of healing still remains a problem among orthopedic surgeons. An acoustic technique based on stress-wave propagation is developed. The technique is used on laboratory experimental in vitro bones, as well as on in vivo (human) bones, to diagnose a fracture. The rate of healing of the fracture is also studied. The technique developed is quick, economical, reliable, portable, and safe for both the patient and the operator. PMID- 2249861 TI - A compartment model for fluorometric indication of tissue perfusion. AB - Sodium fluorescein is an in vivo blood perfusion indicator for soft tissue. When fluorescein dye is introduced into the blood, it distributes throughout the vasculature and the extravascular space. Incident light from an external source causes the dye to fluoresce, the level of which is monitored by a photodetector placed over the tissue. In this study, theoretical analysis incorporating a multicompartmental model for dye distribution is applied to describe the relationship among perfusion, dye kinetics, and fluorescence readings. Errors in calculating perfusion from fluorescence are related to dye concentrations and to measurement errors. These error sources are minimized by selecting the measurement time. The alternatives of measurement during wash-in or during wash out of dye are compared, as well as the alternatives of introducing dye by bolus injection or by constant infusion. Compensation of wash-in measurements for differences in skin pigmentation is accomplished by the matching of skin optical properties between incident and fluorescing wavelengths. A laboratory study at 80 measurement sites (from ten graded perfusion canine flaps) demonstrated a correlation of wash-in and wash-out perfusion data ranging from 0.88 to 0.96 at typical levels of fluorescein in blood. Since wash-in can be completed in a matter of a few minutes, this is likely to be preferable in the clinical setting to wash-out which can take much longer to complete. PMID- 2249862 TI - Development of a multiple thin-film semimicro DC-probe for intracerebral recordings. AB - A thin-film multiple-electrode probe for measuring de potentials at eight sites with interdistances of 1 mm was constructed for the investigation of slow potential changes in deep regions of the human brain during surgery. The thin film electrodes had to be placed on curved cylinder-shaped surgical instruments with dimensions of 2 mm diameter and 33 cm length used with the Freiburg stereotactic equipment. Several novel technological steps had to be introduced for the solution of the encountered problems: 1) Structuring of the metal layers on curved substrates was accomplished by using flexible masks. 2) Special feed through technologies had to be invented in order to obtain reliable connections between the thin-film sensors and the copper wires inside the stereotactic instrument. 3) Thin-film Ag-AgCl electrodes had to be formed in order to obtain satisfying recordings of slow potential changes below 10 Hz. Slow potential changes were recorded from different depths in interdistances of only 1 mm with these new miniaturized thin film Ag-AgCl electrodes and bipolar recordings with an electrode interdistance of only 3 mm showed clearly the appearance of Bereitschaftspotentials. PMID- 2249863 TI - An application of magnet and magnetic sensor: measurement system for tooth movement. AB - A measurement system for tooth displacement and rotation in the sagittal and frontal planes was designed and tested. Four small magnetic sensors were arranged at each corner of a rectangle on a plastic sheet. They were then placed in the mouth and fixed to the front teeth with a plastic splint. A powerful magnet made of a rare earth metal was fixed to the target tooth and placed at the center of the sensors. Movement of the magnet was detected by the four sensors as the tooth trajectory. This system was tested by measuring first molar movement in human subjects with a load generated by an orthodontic aid. This system was small enough to fit in a human oral cavity and did not interfere with the orthodontic aid. Although the oral environment with high humidity and high temperature was not agreeable for the sensors, resolution was estimated at better than 3 microns including the effects of system drift. System calibration was done extra orally and distortion was calculated at less than 6% in a square of 200 microns. The accuracy of this system was not affected by temperature due to the application in the oral cavity at a relatively constant temperature. The advantage of this system was not only the two-dimensional measurement but also rotational measurement in which a 0.05 degree resolution was calculated. PMID- 2249864 TI - A computerized system for video analysis of the aortic valve. AB - A novel technique was developed to study the dynamic behavior of the porcine aortic valve in an isolated heart preparation. Under the control of a personal computer, a video frame grabber board continuously acquired and digitized images of the aortic valve, and an analog-to-digital (A/D) converter read four channels of physiological data (flow rate, aortic and ventricular pressure, and aortic root diameter). The valve was illuminated with a strobe light synchronized to fire at the field acquisition rate of the CCD video camera. Using the overlay bits in the video board, the measured parameters were super-imposed over the live video as graphical tracing, and the resultant composite images were recorded on line to video tape. The overlaying of the valve images with the graphical tracings of acquired data enabled the data tracings to be precisely synchronized with the video images of the aortic valve. This technique enabled us to observe the relationship between aortic root expansion and valve function. PMID- 2249865 TI - Estimation of regurgitant volume and orifice in aortic regurgitation combining CW Doppler and parameter estimation in a Windkessel-like model. AB - A method for noninvasive estimation of regurgitant orifice and volume in aortic regurgitation is proposed and tested in anesthetized open chested pigs. The method can be used with noninvasive measurement of regurgitant jet velocity with continuous wave ultrasound Doppler measurements together with cuff measurements of systolic and diastolic systemic pressure in the arm. These measurements are then used for parameter estimation in a Windkessel-like model which include the regurgitant orifice as a parameter. The aortic volume compliance and the peripheral resistance are also included as parameters measurements in the open chest pigs are used. Electromagnetic flow measurements in the ascending aorta and pulmonary artery are used for control, and a correlation between regurgitant volume obtained from parameter estimation and electromagnetic flow measurements of 0.95 over a range from 2.1 to 17.8 mL is obtained. PMID- 2249866 TI - A comparison of response characteristics of airflow and pressure transducers commonly used in rhinomanometry. AB - Although the ranges in which pneumotachographs evidence linear output to static flows are documented in the literature, measures of output reliability or the stability of calibration functions resulting from the input of dynamic nonsinusoidal flows (such as those which occur during nasal breathing) have not been investigated. Furthermore, it is not known whether the type of requisite pressure transducer used in conjunction with the pneumotachograph influences the pneumotachograph's linearity, output reliability, or dynamic response. To provide information on these points, we determined the dynamic and static responsiveness of three pneumotachographs commonly used in rhinomanometry, in combination with three requisite pressure transducers. In general, a) output reliability depended on the pneumotachograph/pressure transducer combination and was not readily predictable from the reliabilities of the individual components, b) heating increased pneumotachograph reliability, and c) differences in accuracy existed among transducer combinations at high, but not low, flow frequencies. In addition, results from the calibration syringe study (in which the pneumotachograph is calibrated with dynamic non-sinusoidal flows) suggested that: a) a single calibration factor, as supplied by most pneumotachograph manufacturers, is inadequate for accurately measuring the full range of flows produced in sniffing and breathing tasks; b) the measurement of complex waveforms, even when the dominate frequencies of such waveforms are low, requires pneumotachographs that accurately respond to relatively high frequencies; and c) the use of dynamic nonsinusoidal flows (as opposed to static flows) to calibrate pneumotachographs results in a calibration function with higher reliability. PMID- 2249867 TI - Multicategory classification of body surface potential maps. AB - A statistical classification method is suggested for body surface potential maps (BSPM). The initial data reduction utilizes the Fourier expansion and time integration, resulting in physiological-oriented features. Based on Fischer's criterion, optimal discriminant vectors are used to map the features to an optimal subdomain. Experimental criteria determine the dimensionality of the subdomain and the number of features to be mapped into it. Classification is performed in two steps. In the first, a k-nearest neighbor (k-NN) rule is used for every two-category problem, the results of which are fed into a voting rule for final classification. The method is tested with 123 patients divided into four categories: normal (NR), ischemia (IS), myocardial infarction (MI), and left bundle branch block (LB) patients. The success is between 88% (for IS) and 100% (for LB) for QRS segment integration. Departure maps were used to explain the misclassified patterns. PMID- 2249868 TI - The role of intramyocardial pressure during coronary sinus interventions: a computer model study. AB - A model consisting of an arterial, a capillary, and a venous compartment was developed to reproduce experimentally determined hemodynamic results of the arterial and venous sides of the coronary circulation. From the model, intramyocardial flow between capillaries and veins, which is inaccessable to measurement, was then estimated. Results are given for normal perfusion and coronary sinus occlusion conditions. For both conditions, intramyocardial pressure was varied within the model in order to study its impact on intramyocardial flow. For low and moderate intramyocardial pressures under coronary sinus occlusion, retrograde flow from veins to capillaries was seen to increase with increasing intramyocardial pressure. However, for very high values of intramyocardial pressure, which are close to left ventricular pressure, retrograde flow declined. PMID- 2249869 TI - On-line pressure estimation for a left heart assist device. AB - Long term measurement of blood pressures is essential for control of circulatory systems with artificial hearts or circulatory assist devices. Efforts to obtain reliable continuous direct measurements of blood pressures, however, have not been successful. This paper describes an on-line pressure estimation technique for use with a portable pneumatically driven left heart assist device. The on line maximum likelihood algorithms are used for the estimation with the technique based on the use of physical models of the components of the driver and blood pump system. This technique estimates the inlet and outlet pressures of the blood pump. The directly measured driving air pressure and piston position of the pneumatic actuator are used for the estimation. In vitro and in vivo experiments were made to test the use of the on-line estimation technique. The results show successful linear correlations between the actual pressures and their estimates. This technique offers the following advantages: accurate pressure information for on-line control, accessibility to the transducers for recalibration, and noninvasive location of the transducers. PMID- 2249870 TI - A three-dimensional iterative scheme for an electromagnetic capacitive applicator. AB - An efficient iterative method for solving quasi-static electromagnetic field problems is presented. A relaxation function is introduced in the quasi-static field equations. Then, the resulting equations can be solved by iteration. The method is similar to the one of solving a Laplace equation by computing the stationary state of a diffusion equation. Next, for a radially layered configuration the numerical results are compared with the results from an existing integral equation method. Subsequently, for a realistic three dimensional model of a human knee numerical results are arrived at. PMID- 2249871 TI - Optimal excitation of multiapplicator systems for deep regional hyperthermia. AB - A method is proposed for determining the excitation amplitudes and phases of the elements of electromagnetic multiapplicator systems for optimizing the specific absorption rate (SAR) distribution around a deep-seated tumor. In this method, the ratio of the power dissipated in the tumor to a weighted summation of the powers supplied to the surrounding regions is optimized. The optimization procedure is combined with a recently proposed effective technique for analysis of various electromagnetic scattering and interaction problems. The general principle is applied to a two-dimensional problem of a piecewise homogeneous cylinder heated by an array of electric current filaments placed outside the cylinder. Numerical simulations are performed to check the effectiveness of the approach. The results demonstrate that using this optimization method, improved SAR distributions can be achieved. The extension to three-dimensional configurations is discussed. PMID- 2249872 TI - Charge density and charge per phase as cofactors in neural injury induced by electrical stimulation. AB - The possibility of neural injury during prolonged electrical stimulation of the brain imposes some constraints on the use of this technique for therapeutic and experimental applications. Stimulating electrodes of various sizes were used to investigate the interactions of two stimulus parameters, charge density and charge per phase, in determining the threshold of neural injury induced by electrical stimulation. Platinum electrodes ranging in size from 0.002 to 0.5 cm2 were implanted over the parietal cortex of adult cats. Penetrating microelectrodes fabricated from iridium, with surface areas of 65 +/- 3 x 10(-6) cm2 were inserted into the parietal cortex. Ten days after implantation, the electrodes were pulsed continuously for 7h using charge balanced, current regulated, symmetric pulse pairs, 400 microseconds per phase in duration, at a repetition rate of 50 Hz. The animals were perfused immediately after the stimulation for histologic evaluation of the brain tissue subjacent to the electrode sites. The results show that charge density (as measured at the surface of the stimulating electrode), and charge per phase, interact in a synergistic manner to determine the threshold of stimulation-induced neural injury. This interaction occurs over a wide range of both parameters; for charge density from at least 10 to 800 microC/cm2 and, for charge per phase, from at least 0.05 to 5.0 microC per phase. The significance of these findings in elucidating the mechanisms underlying stimulation-induced injury is discussed. PMID- 2249873 TI - The interleukin-2 receptor on cord blood and nulliparous mononuclear cells is downregulated by maternal and cord blood serum. AB - The concentration of interleukin-2 receptor (IL-2R) on maternal, cord blood and unrelated nulliparous mononuclear cells has been studied after a previous phytohaemagglutinin (PHA) stimulation. Furthermore, the inhibitive action of maternal and cord blood serum on the IL-2R expression of stimulated nulliparous and cord blood lymphocytes has been shown. A downregulation of the [3H]-thymidine uptake by these PHA treated cells previously incubated in maternal and cord blood serum has been observed. Retroplacental serum was the most inhibitive experimental medium. The IL-2R modulation property of maternal serum has been studied during the pregnancy. Appearing quite early (in the sixth week), the maternal serum dependent inhibitive factor vanished, 2 to 3 weeks after delivery. After a study of the different serum components, it is suggested that the IL-2R downregulating molecule is included in the maternal immunoglobulin (IgG) fraction. Further experiments suggest that the addition of recombinant IL-2 during the action of low doses of maternal IgG allows a partial re-expression of the IL-2R. However, at physiological concentrations of IgG, the IL-2R downregulation becomes irreversible. PMID- 2249874 TI - Production and characterization of a new monoclonal antibody to colorectal carcinoma. AB - This study describes a new murine monoclonal antibody (MoAb) 5C1 raised against human colorectal carcinoma, which gave a differential reaction on formalin-fixed sections of the gastrointestinal tract. The MoAb 5C1 of immunoglobulin M (IgM) isotype reacted with both the cytoplasm and membrane of all normal colonic epithelia, and with all benign colonic polyps and all premalignant colonic lesions. However, there was a decreased expression of the 5C1 antigen in most cases of colonic malignancy and it was this feature that makes MoAb 5C1 unique. The distribution of the 5C1 epitope in normal gastrointestinal tract is limited to a few epithelial cells in the mid-portion of the small intestine but this distribution increased progressively down the digestive tract until it was found on greater than 90% of normal epithelial cells (in membrane and cytoplasm) of the colon. In addition, the 5C1 epitope was present on mucin secreting cells from normal organs of the gastrointestinal, reproductive and pulmonary tract and benign and malignant tissues of the colon. On Western blots, MoAb 5C1 was found to detect a heterogeneous population of molecules with molecular weights greater than 100 kDa with the strongest staining bands found between 230 and 300 kDa. MoAb 5C1 does not detect carcino-embryonic antigens (CEA), human milk fat globules (HMFG), human lymphocyte antigens (HLA) or ABO blood group antigens. The combination of its presence in mucin secreting cells and its broad molecular weight bands suggest that the antigen detected is a mucin. PMID- 2249875 TI - Production of a monoclonal allo-antibody to murine natural cytotoxic cells. AB - A mouse IgG1 monoclonal antibody (1C4), which recognizes a cell surface molecule on murine natural cytotoxic (NC) cells was produced. By flow cytometry, 1C4 preferentially reacted with less than 5% of fresh CBA spleen cells and 20-50% of CBA-interleukin-3 (IL-3) cells, an in vitro derived NC-like cell line. In vitro treatment of spleen cells from a number of inbred mouse strains either with 1C4 alone or 1C4 coupled to dynabeads markedly decreased or abolished NC activity of the cells against 51Cr-labelled WEH1-164 targets. Splenic NC activity of these same mouse strains was also reduced or abolished by in vivo administration of 1C4. The effect was evident within 2 h of treatment and persisted for at least 1 week. In contrast 1C4 had little or no effect on splenic NK activity against 51Cr labelled YAC-1 targets over the same range of experiments in vitro and in vivo. Results of strain surveys for both in vitro and in vivo reduction of splenic NC activity by 1C4 treatment showed that CBA, C57BL/6, BALB/c and NZB mice were positive and CE and DBA/2 mice were negative, indicating that 1C4 recognizes an allo-antigen on mouse NC cells. This allo-antibody has been designated NC-1.1, and thus 1C4 is an anti-NC-1.1 monoclonal antibody. PMID- 2249876 TI - Special differentiation requirements of original and enriched secondary cytotoxic T lymphocyte precursors (pCTL-2 memory cell) specific for the class I histocompatibility molecule. AB - The in vivo-induced pCTL-2 cells of the L3T4- Lyt-2+ phenotype specific for the H 2Kb molecule are converted into effector CTLs in mixed lymphocyte culture (MLC) in the presence of heat-treated donor stimulators much more efficiently when the donor and recipient differ from each other, not only in the major histocompatibility complex (MHC) class I (H-2Kb) (anti-B10.MBR B10.AKM) but also in the MHC classes I + II, i.e., Kb + Ib (anti-C57BL/6 B10.D2 (R101)). The differentiation of original pCTL-2 is enhanced as the result of a synergistic action of the Kb alloantigen and rIL-2 in small doses. The anti-Kb pCTL-2, after their separation from helper T cells non-adherent to the macrophage donor monolayer and their subsequent elution from it, give rise to pronounced differentiation in simplified conditions over 3 days in monoculture in the absence of both stimulators and rIL-2. It is suggested that spontaneous and highly efficient specific differentiation of the eluted pCTL-2 is due to a dramatically enhanced secretion of the CTL differentiation factor by pCTL-2 themselves, and in addition, rIL-2 can also contribute to the secretion of this factor. PMID- 2249877 TI - Interleukin-1 and tumour necrosis factor alpha induced polymorphonuclear leukocyte-endothelial cell adhesion and transendothelial migration in vitro: the effect of apical versus basal monolayer stimulation. AB - The cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha) enhance polymorphonuclear leukocyte (PMNL) adhesion to vascular endothelium by an endothelial cell dependent mechanism in vitro and induce PMNL infiltration in vivo In this study, we employed human umbilical vein endothelium (HUVE) cultured on microporous membrane filters to form a monolayer, a system in which PMNL adherence and PMNL transendothelial migration could be measured using 51Cr labelled human PMNL. In this system, it was found that PMNL adhesion and migration were dependent on prior treatment of the HUVE monolayer with IL-1 or TNF alpha for at least 2 h and that cytokine could be removed prior to the addition of PMNL without any effect on the response. PMNL adherence to the HUVE was maximal by 30 min and was followed by progressive migration of PMNL across the monolayer and the membrane filter into the lower chamber. The effect of apical surface versus basal surface exposure of the HUVE monolayer to IL-1 alpha and TNF alpha on subsequent PMNL interaction with the HUVE monolayer in the absence of cytokine was examined. Apical or basal stimulation induced comparable PMNL adherence at 30 min following addition of PMNL (35.5% and 43.1%). However, basal (i.e., abluminal) exposure to IL-1 or TNF alpha of the HUVE induced significantly greater PMNL transendothelial migration (e.g., 27.8% vs. 15.4%; P less than 0.01). The expression of endothelial-leukocyte adhesion molecules ELAM 1 and ICAM-1 following apical versus basal stimulation was determined by ELISA on viable cells. These adhesion molecules were upregulated to a similar extent under both conditions. These observations suggest that spacial localization or orientation of adhesion molecules may be influenced by basal versus apical cytokine stimulation or that other mechanisms are responsible for the preferential PMNL migration with basal stimulation. These findings may have implications for the in vivo interactions of PMNL with vascular endothelium, depending on whether the endothelium is exposed to IL-1 of TNF alpha via the blood on the luminal (apical) surface or via the extravascular space on the abluminal (basal) surface. PMID- 2249878 TI - Reduction by OK-432 of the monolayer contact-mediated inhibition of human natural killer cell activity. AB - In the present study we investigated the effect of OK-432, a streptococcus preparation, on the contact-mediated inhibition of human NK activity by primary cultures of monolayer cells. Either peripheral blood lymphocytes (PBL) or large granular lymphocytes (LGL) were incubated (2 x 10(6) cells/ml, total volume 2 ml) on confluent monolayer cells (uvea-derived fibroblasts, uvea-derived melanoma cells, or renal carcinoma cells) for 18 h in 24-well plates, washed twice, and tested for cytotoxicity against K562, a human myelogenous leukemia cell line, in a 4 h 51Cr-release assay. After contact with monolayer cells, NK activity of both PBL and LGL was significantly reduced. When these effector cells were preincubated with 0.1 U/ml of OK-432 for 18 h and then tested for the sensitivity to contact-mediated inhibition, the inhibition was significantly reduced. The pretreatment of monolayer cells with OK-432 or the addition of OK-432 into the coculture wells (of effector cells and monolayer cells) also significantly reduced the contact-mediated inhibition. Moreover, OK-432 (0.1 U/ml) reestablished the inhibited NK activity of PBL. These results suggest that OK-432 might enable NK cells to escape from the contact-mediated inhibition by monolayer cells and thus provide an additional potential mechanism for the observed clinical effectiveness of OK-432 reported by many groups. PMID- 2249879 TI - Molecular characterization of human complement factor B subtypes. AB - While several laboratories have agreed that there are two subtypes of the BF*F alleles, no information has been available until now at the molecular level. The region of the BF gene corresponding to the Ba fragment [1.7 kilobases (kb)] of the BF*S, BF*FA, and BF*FB alleles has been sequenced after specific amplification using the polymerase chain reaction (PCR). A point mutation at codon 7 has been revealed converting a cytosine in the BF*S allele to a thymidine in BF*FB. At the translational level an arginine residue in BF*S is substituted for a tryptophan residue in BF*FB. The amino-terminal sequencing of factor B immunoprecipitated from serum has been carried out from microquantities of protein blotted onto polyvinylidene fluoride (PVDF) membranes. We have shown that the difference between the BF*FA and the BF*FB subtypes in characterized by a glutamine at position 7 in BF*FA and a tryptophan in BF*FB. PMID- 2249880 TI - Sequence analysis and HLA-DR genotyping of a novel HLA-DRw14 allele. AB - Analysis of a Japanese population by oligonucleotide genotyping revealed that one Japanese HLA-DRw14 allele had a DRB1 genotype different from that of the known HLA-DRw14-related alleles, DRB1*1401 (DRw14-Dw9) and DRB1*1402 (DRw14-Dw16). The second exon of the DRB1 gene of the novel DRw14 allele (designated DRB1-14c) was amplified enzymatically and sequenced after cloning into a plasmid vector. The amino acid sequence of the first domain in the DR beta 1 chain encoded in the DRB1-14c allele was more similar to that of the DRB1*1401 allele (three amino acid substitutions) than to that of the DRB1*1402 allele (six amino acid substitutions). No polymorphic amino acid residue that could explain the common serologic HLA-DRw14 specificity was identified among the sequences of the three DRw14-related alleles. Sequence-specific oligonucleotides (SSOs) were synthesized on the basis of the DRB1-14c nucleotide sequence and used for genotyping of the Japanese population. These SSOs served as useful probes for identifying the DRB1 14c allele in a wide range of donors. PMID- 2249881 TI - Experimental allergic orchitis in mice. VI. Recombinations within the H-2S/H-2D interval define the map position of the H-2-associated locus controlling disease susceptibility. AB - Susceptibility to autoimmune orchitis is associated with an immune response (Ir) gene (now designated Orch-1) which was preliminarily shown to reside at or near the H-2D subregion of the major histocompatibility complex in the mouse (H-2). In this study, the role of H-2 in controlling both disease susceptibility and the phenotypic expression of infertility associated with autoimmune orchitis has been significantly extended. Of nine C57BL/10SnJ and three BALB/cAnN H-2 congenic strains, only those mice possessing the H-2d, H-2p haplotypes exhibited autoimmune orchitis accompanied by infertility. All other congenic strains, including those expressing the H-2 haplotypes v, q, b, s, r, f, and k were of the low responder phenotype. In addition, disease susceptibility was found to be inherited as a dominant trait in H-2 congenic F1 hybrid mice. In order to map the precise location of the Orch-1 locus within H-2, 32 intra-H-2 recombinant congenic strains possessing defined crossovers in various locations throughout the H-2 region were studied. The results of the analysis indicate that Orch-1 maps within the interval between the H-2S and H-2D regions. Our results also indicate that class II genes, i.e., A and E region-encoded genes, have little discernable effect in controlling disease susceptibility and resistance despite the fact that testicular lesions can be adoptively transferred with Ia-restricted CD4+ effector T cells. A comparison of the Orch-1 alleles with the genotypes of two additional markers which map within the H-2S/H-2D interval suggests the following gene order: H-2S--TNP-Ficoll--Orch-1--Tnfa--H-2D. PMID- 2249883 TI - Tables--an endangered species. PMID- 2249882 TI - HLA antibody responses in HLA class I transgenic mice. AB - In a previous report we described how cross-immunizations of pairs of transgenic mice expressing different HLA class I antigens led to the production of antibodies directed exclusively at polymorphic epitopes. This was ascribed to self-tolerance of HLA that prevents immune responses to monomorphic epitopes and focuses responses on polymorphic ones. In the present report we extend our findings and demonstrate that immunizations of class I transgenic mice with HLA transfected mouse fibrosarcoma as well as with human lymphoblastoid cells also preferentially yield antibodies to polymorphic epitopes. This was the case whether or not immunizations were carried out across locus barriers [e.g., Tg(HLA A *0201) or Tg(HLA-Cw*0301) transgenic mice immunized with HLA-B27 transfectants] or within the same locus [e.g., Tg(HLA-B*1302) transgenic mice immunized with HLA B27 transfectants or B27-expressing lymphoblastoid cells]. Use of an extended immunization protocol with four or more booster injections favored antibodies of IgG isotype with affinities high enough to lyse normal peripheral blood lymphocytes (PBLs) in complement-dependent cytotoxicity assays and to immunoprecipitate HLA antigens. The specificities covered by the monoclonal antibodies (mAbs) could be either broad or narrow, depending on the genetic distance of the HLA antigens or alleles involved. For instance, a Tg(HLA-B*1302) transgenic mouse immunized with B27 produced both broad B7/B27-specific antibodies, Bw4-specific antibodies, and one antibody reacting with all B alleles except B13 and with some C alleles. On the other hand, a Tg(HLA-B*1302) transgenic mouse immunized with Bw47 transfectants responded narrowly with an antibody to Bw60 and Bw47. Thus it appears that by choosing appropriate recipient mice and closely related or more distant HLA antigens, antibodies of a programmed specificity can be generated. PMID- 2249884 TI - Antiinflammatory reactivity of copper(I)-thionein. AB - In unseparated human blood the reactivity of yeast copper (I)-thionein on TPA activated polymorphonuclear leukocytes was evaluated and compared with low Mr copper chelates exerting Cu2Zn2 superoxide dismutase mimetic activity. Cu, 18 microM, in the form of Cu-thionein was sufficient to inhibit the superoxide production of activated human blood phagocytes by 50%. Furthermore, the scavenging of hydroxyl radicals and singlet oxygen by Cu(I)-thionein was determined, using the 2-deoxyribose fragmentation assay induced by decaying K3CrO8 and the NADPH oxidation caused by UVA illuminated psoralen, respectively. The inhibitory reactivity of Cu-thionein in both assays was compared with that of serum proteins including albumin, ceruloplasmin, transferrin, and ferritin. The galactosamine/endotoxin-induced hepatitis in male NMRI mice was used to evaluate the antiinflammatory reactivity of Cu-thionein in vivo. The serum copper, superoxide dismutase, and sorbitol dehydrogenase concentrations, as well as the activity of polymorphonuclear leukocytes in unseparated blood seemed most appropriate to quantify the protective capacity of Cu-thionein in the course of an oxidative stress-dependent liver injury. The intraperitoneal application of 32.5 mumols/kg thionein-Cu limited this damage to 45%. PMID- 2249885 TI - A monoclonal-antibody-defined adhesion-related antigen on bovine neutrophils is required for neutrophil aggregation. AB - Surface adhesion molecules present on human leukocytes are known to regulate certain adhesion-related events, such as adhesion to endothelium, extravasation, and aggregation. We have used a mouse anti-human monoclonal antibody designated 60.3 (MAb 60.3) and indirect immunofluorescence technique to identify an antigen on bovine neutrophils (PMNs). MAb 60.3 bound to resting and stimulated bovine PMN in a surface-oriented pattern. Immunofluorescence flow cytometric analysis indicated that warming the PMNs from 4 degrees C to 37 degrees C slightly increased (13.9%) expression of the antigen recognized by MAb 60.3. Zymosan activated serum (ZAS, 10%) increased antigen expression by 12.4% over those PMNs in buffer alone, and phorbol 12-myristate 13-acetate (PMA; 100 ng/ml) by 65.6%. Bacterial lipopolysaccharide (LPS; 1 micrograms/ml) from E. coli 0111:B4 did not enhance antigen expression. The functional nature of this antigen was demonstrated by use of MAb 60.3 and PMN aggregation. Preincubation of bovine PMN with MAb 60.3 for 10 min resulted in nearly complete inhibition of PMN-PMN aggregation upon subsequent stimulation with PMA (100 ng/ml); preincubation with a control antibody did not inhibit aggregation. These results indicate that bovine PMNs possess surface molecule(s) that may function in adhesion-related events, and surface expression may be enhanced by PMN stimulation. PMID- 2249886 TI - Time-dependent inhibition of oxygen radical induced lung injury. AB - Experimental acute lung injury mediated by reactive metabolites of oxygen can be inhibited by the antioxidant enzymes catalase and superoxide dismutase (SOD). However, the specific time interval during which these enzymes must be present in order to cause protection is not well defined. Using two experimental models of oxidant-dependent acute lung injury, one involving the intratracheal injection of glucose, glucose oxidase, and lactoperoxidase and the other involving the intravenous injection of cobra venom factor (CVF), we investigated the effects of delaying antioxidant administration on the outcome of the inflammatory response. In both cases, the protective effects of catalase and SOD were rapidly attenuated when their administration was delayed for a short period of time. For example, intratracheal catalase resulted in 98% protection when given simultaneously with the glucose oxidase and lactoperoxidase, but only 13% protection when the catalase was delayed 4 min. Likewise, in the CVF-induced lung injury model, intravenous catalase resulted in 40% protection when given simultaneously with the CVF, but only 2% protection when the catalase was delayed 20 min, even though the peak of the injury occurred hours after the initiation of the injury. A similar time dependence was seen with SOD. These results indicate that antioxidant therapy is required early in the course of oxygen radical-mediated acute lung injury for effective protection. PMID- 2249887 TI - Characterization of leukocyte chemotactic activity of bacteriocin from Streptococcus mutans Rm-10. AB - Bacteriocins have several biological activities in addition to their antibacterial effect. We investigated the chemotactic properties and mode of action of purified streptococcal bacteriocin. Bacteriocin purified from a culture supernatant of Streptococcus mutans (S. mutans) Rm-10 induced chemotaxis of human polymorphonuclear leukocytes and monocytes. Following purification, leukocyte migration appeared in one bacteriocin fraction, and this migration was dependent on the concentration gradient in dilution ranges from 1/960 to 1/15. Chemotactic activity of the bacteriocin was heat labile and trypsin sensitive. Moreover, preincubation of bacteriocin with varying dilutions of its antiserum prepared in rabbits resulted in a significant loss of the chemotactic activity. PMID- 2249888 TI - Human phagocytic cells as oxygen metabolite scavengers. AB - Human neutrophils or monocytes decreased hydrogen peroxide (H2O2) concentrations in vitro. Neutrophils or monocytes decreased H2O2 concentrations as well as human erythrocytes. Treatment with aminotriazole or azide decreased both phagocyte and erythrocyte catalase activity and the ability of each cell to decrease H2O2 concentrations in vitro. Prestimulation of phagocytic cells with phorbol myristate acetate (PMA) or opsonized zymosan decreased neither their catalase activity nor their ability to decrease H2O2 concentrations. The results suggest that unstimulated or stimulated phagocytic cells can scavenge H2O2 and may potentially decrease H2O2-mediated tissue injury. The H2O2 scavenging potential of phagocytic cells is due at least partially to their catalase activity. PMID- 2249890 TI - Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption. AB - The role of different types of alcoholic beverage on cancer of the upper digestive tract was investigated in a case-control study conducted in the northern part of Italy on 305 male cases of cancer of the oral cavity and pharynx, 288 of oesophageal cancer and 1621 controls admitted to hospital for acute, non-neoplastic conditions, unrelated to alcohol intake. Similar significant trends of risk increase with increasing alcohol intake were seen for cancers of the oral cavity, pharynx and oesophagus independent of type (or types) of beverage consumed. Among the heaviest drinkers (i.e. greater than or equal to 84 drinks/week) odds ratios (ORs) of cancer of the oral cavity and pharynx for wine only, wine and spirits, and combination of wine, spirits, and beer were 11.2, 9.9 and 4.1, respectively. Corresponding oesophageal cancer ORs were 15.0, 10.0 and 6.0. This study from an area with high wine consumption confirms that wine per se can greatly enhance the risk of cancer of the upper digestive tract and suggests that the most frequently used alcoholic beverage in each study appears to be the most important determinant of these tumours. PMID- 2249889 TI - Mitogenic peptides in breast cyst fluid: relationship with intracystic electrolyte ratios. AB - Women with palpable breast cysts which are lined with apocrine epithelium may be at higher risk of developing breast cancer than women with breast cysts which are lined with flattened epithelium, the former group being characterized by intracystic sodium to potassium ratios below 3, while the latter group has intracystic sodium to potassium ratios above 3. In this study the distribution of intracystic concentrations of the mitogenic peptides, epidermal growth factor, endothelin and gastrin-releasing peptide in the 2 groups of breast cysts were compared to see whether differences in concentrations between the 2 cyst groups might provide an explanation for the higher risk of breast cancer observed in women with "apocrine" breast cysts. The concentrations of epidermal growth factor and gastrin-releasing peptide were significantly higher in the low electrolyte ratio group (p less than 0.001). There was no difference in endothelin concentrations between the 2 groups. Negative correlations were found between epidermal growth factor concentrations and Na+/K+ and between gastrin-releasing peptide concentrations and Na+/K+ (p less than 0.001). A positive correlation was found between gastrin-releasing peptide and epidermal growth factor concentrations in breast cyst fluid (p less than 0.001). The significantly higher intracystic concentrations of both epidermal growth factor and gastrin-releasing peptide in the low-electrolyte-ratio group may provide an explanation for the higher risk of breast cancer which has been observed in women with "apocrine" breast cysts. PMID- 2249891 TI - Potentiation of TNF-mediated cell killing by VP-16: relationship to DNA single strand break formation. AB - Interaction between tumor necrosis factor (TNF) and the DNA topoisomerase II inhibitor, etoposide VP-16, in cell killing has been studied. To accurately investigate the nature of DNA damage during the cell killing process, experiments were assessed using the highly TNF-sensitive WEHI164.13 murine fibrosarcoma clone and DNA filter elution methodology. Concomitant treatment of cells with combination of TNF/VP-16 resulted in marked enhancement of cell lysis. Using the alkaline elution technique, we show that TNF fails to induce DNA single-strand breaks as compared to those generated by VP-16. In addition, the potentiating effect of VP-16 on TNF-mediated WEHI164.13 cell killing was not associated with an increase in its intrinsic activity with respect to DNA single-strand break formation. While the 2 phospholipase A2 inhibitors, quinacrine and dexamethasone, were efficient in inhibiting TNF-mediated cell lysis, only quinacrine was efficient in selectively abrogating the TNF/VP-16 cell killing pathway. The inhibitory effect of quinacrine on VP-16/TNF-mediated cell lysis was accompanied by a marked decrease in VP-16-mediated DNA single-strand break generation. Taken together, our findings suggest that TNF and TNF/VP-16 treatments may involve different events during cell killing and support the hypothesis that 2 signals are required for optimal induction of cell lysis by the combination of VP-16/TNF: one signal provided by VP-16 resulting in topoisomerase II inhibition and subsequent DNA single-strand break generation, and a second signal involving TNF. PMID- 2249892 TI - Effect of retinoic acid on tumor-mediated immunologic alterations in mice bearing a variant of the B16 melanoma. AB - This investigation examined the effect of retinoic acid on tumor progression and immunological status of mice bearing the B16-F10 melanoma (previously selected for high lung-colonizing capacity). Tumor cells were implanted s.c. in syngeneic C57BL/6 mice, half of which were treated with beta-all trans retinoic acid (RA). Although RA failed to exhibit direct toxicity on this variant at the concentration used, the immunologic aberrations induced by the tumors were diminished by i.p. RA administration (at 45 micrograms twice/week for 3 weeks). In mice bearing B16-F10 tumors, tumor burdens were decreased from 2.9% of body weight to 1.6%. The mitogenic responses of splenic lymphocytes to concanavalin A (ConA) were increased in tumor-bearing mice following this RA treatment. The presence of these tumor cells decreased the absolute number of CD4- and CD8 positive splenic lymphocytes. Following RA treatment, the CD8-positive population was increased in tumor-bearing mice, while the CD4+ population was not significantly altered. Since previous studies indicated that plasma membrane fragments (or vesicles) could alter lymphocyte distributions and proliferative capacities, the in vitro shedding of membrane fragments from B16-F10 tumor cells was assayed and observed to be decreased after continuous treatment of cultures with 10(-6) M RA for 21 days. Membrane shedding from B16-F10 cells was inhibited by 48.5% following RA treatment. Based on these in vivo and in vitro results, we suggest that RA treatment may diminish tumor growth by decreasing tumor-induced immunosuppressive events. PMID- 2249893 TI - Characterization of a sialic-acid-rich mucus glycoprotein secreted by a premalignant human colorectal adenoma cell line. AB - The human colonic cell line PC/AA, derived from an adenoma, retains in vitro colonic cell differentiation, notably the production of mucus glycoproteins. The PC/AA adenoma cells produce an extracellular gel layer in culture. The PC/AA gel could be isolated by extraction of the cell cultures with guanidine hydrochloride. The extracted material was purified by gel filtration and caesium chloride density-gradient centrifugation and showed properties typical of mucus glycoproteins, namely, a carbohydrate content above 60% of dry weight rich in N acetylgalactosamine and sialic acid and low in mannose; an amino acid composition with high serine threonine and proline content; a molecular weight above 1,000 kDa on Sepharose CL 4B chromatography and on SDS-polyacrylamide gel electrophoresis under reducing conditions (greater than 200 kDa); a buoyant density of approximately 1.48 g/ml and the release of oligosaccharides by the alkaline beta-elimination reaction. Comparison of the gel mucus glycoprotein purified from premalignant PC/AA cells with normal human colon mucin showed that it has a higher sialic acid content. This suggests that higher sialic acid levels may precede the development of malignancy. PMID- 2249894 TI - Transfection of a non-metastatic diploid rat mammary epithelial cell line with the oncogenes for EJ-ras-1 and polyoma large T antigen. AB - Transfection of rat mammary (Rama) 37 epithelial cells which yield non metastasizing adenomas in syngeneic Wistar-Furth rats with a drug resistance plasmid containing both the neo gene and EJ-ras-1 (pSV2neo.ras) or with pSV2neo and a plasmid encoding the large T Antigen (pLT214) of polyoma virus yields drug resistant transformants with a frequency of 10(-5). Representative transformants have been propagated in neo-selecting medium to yield various cell lines. The 7 lines transfected with pSV2neo.ras (EJ1 set) and the 10 lines co-transfected with pSV2neo and pLT214 (LT1 set) all produce tumours at subcutaneous (s.c.) sites with a shorter median latent period than tumours produced by the parental Rama 37 cells. In addition, the LT1 set of transformants yields a higher incidence of tumours than the Rama 37 cells. No metastases are produced when any of the oncogene transformants are inoculated s.c. into rats. However, when an EJ1 representative is inoculated intravenously (i.v.), tumour deposits are found in the lungs of the host animals. In contrast, other Rama 37 variants that metastasize from s.c. sites fail to produce any metastases when inoculated i.v. The oncogene transfectants contain integrated DNA that hybridizes to neo and to the requisite oncogenic DNAs; the pattern of hybridizing bands to the transfected genes and their expression as mRNA is complex, and is presented in detail. PMID- 2249895 TI - Steroid hormone receptor gene expression in human breast cancer cells: inverse relationship between oestrogen and glucocorticoid receptor messenger RNA levels. AB - The relative expression in human breast cancer cells of messenger ribonucleic acids (mRNA) encoding different steroid hormone receptors is unknown. Accordingly, mRNA levels in total RNA extracted from 13 human breast cancer cell lines were measured by Northern analysis employing complementary DNA probes for the human oestrogen (ER), progesterone (PR), androgen (AR), vitamin D3 (VDR) and glucocorticoid receptors (GR). The 7 ER+ lines expressed a single 6.4 kilobases (kb) ER mRNA. Interestingly, low concentrations of ER mRNA were detected in the ER- cell lines, MDA-MB-330 and BT 20. PR mRNA, predominantly a 13.5 kb species, was expressed in the 6 lines known to be ER+, PR+ by radioligand binding; however, one ER+ cell line, MDA-MB-134, failed to express PR mRNA. A 10.5 kb AR mRNA was expressed at significantly higher levels in ER+ than ER- cell lines. All cell lines expressed a single 4.6 kb mRNA for VDR and a single 7.4 kb mRNA for GR. ER and PR mRNA levels were positively correlated (p = 0.011) and each was positively correlated with androgen receptor (AR) mRNA levels (p less than or equal to 0.009). ER, PR and AR mRNAs were negatively associated with GR levels (p less than or equal to 0.012), while ER and AR mRNA levels were negatively correlated with mRNA for the epidermal growth factor receptor. In contrast, levels of VDR mRNA were unrelated to the concentration of any other steroid receptor mRNA. Our data demonstrate the coordinate expression of ER, PR and AR genes, and an inverse relationship between sex steroid hormone receptor and GR gene expression in human breast cancer cell lines. PMID- 2249896 TI - Eradication of a disseminated mouse lymphoma by 1,3-bis(2-chloroethyl)-1 nitrosourea is immunologically mediated and accompanied by de novo generation of anti-tumor cytotoxicity. AB - The anti-tumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YC8). A single i.p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i.v. inoculum of 10(4) YC8 cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5-day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU-cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti-tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2 week period elapsed after BCNU injection before an anti-tumor cytotoxic T lymphocyte (CTL) response could be generated by spleen cells of BCNU-treated 5 day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine-activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU-treated 5-day TB and BCNU-treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14, concomitantly with the generation of anti-tumor cytotoxicity by 5-day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU 1 week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin-2. PMID- 2249897 TI - Augmentation for intratumoral accumulation and anti-tumor activity of liposome encapsulated adriamycin by tumor necrosis factor-alpha in mice. AB - The effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on anti tumor activity of adriamycin entrapped in small unilamellar liposomes (ADM-Lip) has been studied using BALB/c mice bearing subdermal Meth-A fibrosarcoma. Accumulation of i.v. injected ADM-Lip, but not of free ADM, into tumor tissue was augmented by a single i.v. injection of rhTNF-alpha. The maximum effect of rhTNF alpha was expressed when it was injected 1 hr before ADM-Lip. This rhTNF-alpha treatment did not result in increased accumulation of ADM-Lip in normal organs. Based on these results, we treated mice bearing Meth-A tumor with rhTNF-alpha and then with ADM-Lip 1 hr later. By 2-cycle treatments using this regimen, tumor growth was markedly inhibited, and 5 out of 13 mice tested were cured of tumor, while treatment with rhTNF-alpha alone, ADM alone, ADM-Lip alone or rhTNF-alpha plus ADM resulted neither in prolongation of survival time nor in cure of mice. Our results indicate that ADM-Lip can express a potent and systemic anti-tumor activity after pretreatment of animals with TNF, but only when administration of these drugs is appropriately timed. PMID- 2249898 TI - Establishment and characterization of a new human B-cell line (ONHL-1) from non Hodgkin's lymphoma: constant expression of bcl-2 gene during mitogen-induced growth inhibition. AB - A new B-cell line (ONHL-1) was established from non-Hodgkin's lymphoma. ONHL-1 was free from Epstein-Barr virus nuclear antigen and expressed CD20, CD24, and slg (mu, delta, gamma and kappa), thus being equivalent to the mature B-cell stage. Chromosome analysis revealed a markedly abnormal pattern including 14q+ and 6q-. In accordance with the positive expression of surface kappa light chains, one of the kappa genes was found to be rearranged. However, rearrangement of the lambda locus was also detected, contrary to the supposed hierarchy for the rearrangement of the light-chain genes. Further, the rearranged fragments of the JH, C lambda, and bcl-2 genes were of the same size in the EcoRI and HindIII digests on the same filter. This may suggest that the bcl-2 gene is juxtaposed with the JH and C lambda locus. The proliferation of ONHL-I was inhibited by adding Staphylococcus aureus Cowan 1 or 12-O-tetradecanoyl-phorbol-13-acetate. During this growth inhibition, the expression of c-myc decreased, while that of bcl-2 mRNA remained steady. This result suggests that not the bcl-2 gene but other oncogenes, such as c-myc, play a key role in the proliferation of ONHL-1. This agrees with the hypothesis that the bcl-2 gene is not concerned with aggressive proliferation but with cell survival. This new cell line will therefore be of value in studying the differentiation and tumorigenesis of B cells. PMID- 2249900 TI - Increasing gall-bladder cancer mortality rate during the last decade in Chile, a high-risk area. PMID- 2249899 TI - Type-II estrogen binding sites in a lymphoblastoid cell line and growth inhibitory effect of estrogen, anti-estrogen and bioflavonoids. AB - Type-II estrogen-binding sites (type-II EBS) have been demonstrated in the human lymphoblastoid cell line IM-9 using a whole-cell assay with (6,7-3H) estradiol (3H-E2) as tracer. Competition analysis showed that the anti-estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)-E2 binding to type-II EBS. Growth experiments demonstrated that diethylstilbestrol (DES) tamoxifen (TAM), quercetin and rutin exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. The relative binding affinity of quercetin, rutin, DES and TAM for type-II EBS correlated well with their potency as cell growth inhibitors. Moreover, hesperidin, a flavonoid which does not bind to type-II EBS, was ineffective in inhibiting cell growth. Cell-cycle analysis showed that the growth-inhibitory effect of DES, TAM or quercetin was due to a blocking effect in the G0-G1 phases. Our results suggest that high estrogen and anti-estrogen concentrations and flavonoids may regulate IM-9 cell growth through a common mechanism involving a binding interaction with type-II EBS. PMID- 2249901 TI - Polymorphic N-acetylation capacity in breast cancer patients. PMID- 2249903 TI - Reproductive factors and breast cancer risk in Iceland. A second cohort study. AB - In a previous prospective study we showed elevated risks for breast cancer in nulliparous women compared to parous women, in those having their first pregnancy at a higher age, and those with few children. This was based on 216 women diagnosed with breast cancer during 1965 to 1975 among 34,525 women having attended the cervix cancer detection clinic in Iceland by the end of 1974, and born between 1906 and 1945. The present investigation on 848 cases, diagnosed among 61,040 women attending the cervix cancer detection clinic during 1964 to 1984 and born between 1901 and 1960, shows the same risk factors to be significant. The relative risks are, however, smaller. The reasons for the difference in relative risks are discussed. We find that the effect of age at first birth is significant for women up to the age of 65 and not for older women. In both cohorts, women older than 55 are underrepresented and more so in the earlier report. In addition, the small number of cases in the reference group with age at first birth below 20 appears to have made the figures of our earlier report unreliable. PMID- 2249902 TI - Biliary-tract cancer in Chile. AB - This epidemiological study in Chile shows a marked increase in biliary-tract cancer based on mortality data, from an age-adjusted rate (1970 world population) of 5.1 per 100,000 in 1970 to 12.0 per 100,000 in 1988. There is an increased risk of this cancer in all age groups but especially in young adults (15-44 years). The female ratio of 3:1 persists. The increase in biliary-tract cancer in 1970-1985 was particularly important for young women but occurred in all female age groups whereas in men it was mostly in the elderly (65 years and more) and less in the middle-aged (45-64 years); no changes were observed in young men. Regional differences have begun to be appreciated. One of the factors which may account for this impressive and unexpected increase is the remarkable decrease in cholecystectomy rates. Less than 20% of the 154% increase in biliary-tract cancer mortality in the period 1970-1985 could be attributed to population aging. Improvements in diagnostic methods did not appear to be an important contributing factor. Other factors that could affect this increase in the incidence to epidemic levels include: an increase in the prevalence of cholelithiasis, an increase in the number of typhoid carriers and possible environmental carcinogens. PMID- 2249904 TI - Physical activity and colon cancer: a case-referent study in Stockholm. AB - A population-based case-referent study on physical activity (during working and recreational hours) and colon cancer was performed in Stockholm in 1986-1988. The study included 1,081 subjects. Low physical activity was associated with an excess risk of colon (but not rectum) cancer for both men and women, showing a dose-response relationship with decreasing levels of physical activity. The effect was seen in the left colon (relative risk = 3.2, 95% confidence interval = 1.5-7.0) rather than in the right colon (relative risk = 1.1, 0.5-2.5). These results persisted after adjustment for year of birth, gender, body mass, intake of total energy, protein, total fat, dietary fibre, and browned meat surface. PMID- 2249905 TI - Number of children and death from hormone-dependent cancers. AB - The association between number of children of current marriage reported by 431,604 women aged 45-74 years at the Norwegian Census in 1970 and mortality, at follow-up through 1985, from hormone-dependent cancers, i.e., cancers of breast, corpus uteri and ovary combined, has been investigated. The reduction in age adjusted mortality was 9.6% (95% confidence interval; 8.3-10.9%) for each child with no deviation from linearity. Women with 8-11 children had a relative risk of 0.34 (0.25-0.47) compared to nullipara. Adjustment for age at first birth slightly changed the effect of number of children on mortality to 9.3% per child. The reduction in mortality per child was for cancer of the breast 7.2%, corpus uteri 12.2% and ovary 12.7%. Our findings indicate that having few children is a major risk factor for death from the 3 hormone-dependent cancers combined. PMID- 2249906 TI - Uveitis. International meeting to commemorate the 10th anniversary of the International Uveitis Study Group (IUSG). June 29-30, 1989. PMID- 2249907 TI - The natural history of uveitis. AB - Inflammatory diseases of the eye were known to the ancients, but only recently have the underlying mechanisms to this problem become better defined. During the middle portion of this century, most cases of uveitis thought to be caused by infectious agents, such as those responsible for syphilis and tuberculosis. Since then, it has become clear that endogenous mechanisms of immunomodulation play an important role in these disorders, which along with environmental and genetic factors make up an important triad. Animals studies have indicated the pivotal role of the T-cell in many of these disorders. The development of T-cell lines has helped to further delineate cell to cell interactions that occur during an ocular inflammatory event. The presence in the eye of uveitogenic antigens raises the strong possibility of autoimmune driven processes as well, similar to what is seen in the animal models. The better understanding of ocular inflammatory mechanisms has led to improved therapeutic strategies, including Sandimmune, and more recently Cyclosporine G, a related compound that may be less nephrotoxic. Newer therapeutic strategies will focus on even more novel modes of immunomodulation, probably without the use of medications. PMID- 2249908 TI - The role of histopathology in the diagnosis and management of uveitis. AB - Intraocular inflammation/uveitis is one of the more poorly understood areas in the field of ophthalmology. We hope to improve this understanding by first reviewing the classic histopathologic approach to intraocular inflammation, and then by integrating that with the current role of histopathology in the diagnosis and management of uveitis. Herein, we will present a systematic approach, beginning with the most accessible conjunctival, lacrimal gland and lymph node biopsy sites; extending through anterior chamber tap, iris biopsy, and vitrectomy and ending with retinal or chorioretinal biopsy of distant organ sites. We will show how a combination of these histopathologic elements can aid in the diagnosis, and thereby the management, of intraocular inflammations and uveitis. PMID- 2249909 TI - Ocular molecules and cells that regulate immune responses in situ. AB - Regulation of T cell-dependent immune responses is mediated in part by bone marrow-derived antigen presenting cells (APC) that (a) process and present antigens which engage the T cell receptor and (b) secrete cytokines that influence the threshold of T cell activation. The anterior chamber of the eye is lined by the corneal endothelium (which rests on a stroma and epithelium that is devoid of class II MHC + APC) and iris/ciliary body (which contain significant numbers of bone marrow-derived cells, one third of which are class II MHC +). When tested in vitro, these potential APCs fail to present antigens in a form that activates T cells. Moreover, iris/ciliary body cells actually suppress activation of T cells exposed to antigens on conventional APC. In addition, aqueous humor under normal circumstances contains factors (one of which is TGFB) that are potent inhibitors of antigen-driven T cell activation, but spare other aspects of T cell function. Evidence suggests that the bone marrow-derived cells in iris/ciliary body are the source of this factor. Thus, the anterior chamber contains powerful forces that can prevent induction and can suppress expression of T cell mediated immunity. It is proposed that these forces are responsible for immunologic privilege and anterior chamber associated immune deviation, and for suppressing pathologic proliferation and inflammation in the anterior segment of the eye. PMID- 2249910 TI - HLA and uveitis. AB - The association between HLA-A29 and birdshot chorioretinopathy is the strongest of all associations between HLA and disease. Determination of HLA-A29 is even of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker, but B27 positive AAU may be considered as a distinct clinical entity. B27 positive patients with AAU should be referred to a rheumatologist, because half of these patients have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behcet's disease. The present article shows how HLA determinations can serve as diagnostic tests. It is explained how the sensitivity and specificity of such tests can be used to calculate the influence of positive or negative results on the probability of the diagnosis. The structure and function of HLA class I molecules is now known to a great extent. This may lead to a better understanding of the pathogenic role of HLA-A29, HLA B27, HLA-Bw51 and other HLA molecules which are associated with uveitis. PMID- 2249911 TI - Ocular toxoplasmosis. AB - Toxoplasmosis is a common infection of man and animals. The disease is widespread in nature and has a worldwide distribution. The infection is caused by the organism Toxoplasma gondii which was first isolated by Nicolle and Manceaux in Tunis from a North African rodent. The disease can be congenital or acquired with a variety of clinical manifestations that may range from a subclinical course to a generalized infection with fatal outcome. The ocular manifestations of the disease include sudden onset of floaters with blurring of vision. Toxoplasmosis causes a localized necrotizing retinitis with inflammation of the subjacent choroid. The retina sustains the primary injury and the major damage. PMID- 2249912 TI - Ocular toxoplasmosis--clinical aspect. AB - Ocular toxoplasmosis in non immuno-deficients can take 3 major aspects: 1) Pseudo acquired (congenital) forms in teenagers and young adults; 2) Congenital forms in the newborn; 3) Acquired toxoplasmosis. PMID- 2249913 TI - Fuchs' cyclitis: a statistical chronology of its signs. PMID- 2249914 TI - Endemic syphilis (Bejel). PMID- 2249915 TI - Ocular toxocariasis: a presumed case of peripheral granuloma. AB - We report a case of peripheral Toxocara granuloma in a young boy of 17. Of the 3 forms of ocular toxocariasis, macular granuloma, endophthalmitis and peripheral granuloma, the latter is the least common and is characterized by the retention of relatively good vision. A differential diagnosis was performed between an intraocular foreign body encapsulated in fibroglial tissue, toxoplasmic retinochoroiditis, retinoblastoma, intermediate uveitis and toxocariasis. Fluorescein angiography showed not only some neovascularizations at the level of the peripheral granuloma but also manifestations of inflammatory reactions at the level of the posterior pole, i.e. diffuse leakages from retinal capillaries and parietal staining of some venous segments. Among the various laboratory tests, the most significant are eosinophilia, IgE concentration and detection of specific antibodies in serum as well as in aqueous humour. PMID- 2249916 TI - Sarcoidosis--a serious enigma. AB - Sarcoid uveitis is usually chronic and requires treatment with steroids. Severe visual impairment is uncommon unless the disease has been continuously active for years. The mildest form of the disease occurs in Caucasians. PMID- 2249917 TI - Prevention of sympathetic ophthalmia. State of the art 1989. AB - Ophthalmologists are daily confronted with intraocular inflammation following trauma and/or intraocular surgery. In rare cases, this may lead to the loss of visual function in both eyes, i.e. sympathetic ophthalmia (SO). In order to reduce the scope of responsible action between enucleation of the exciting eye (EE), which still has good vision, and progressive inflammation of the second eye (SE) resulting in blindness if action is delayed, a score system was established based on all SO symptoms which had become known from the literature and personal communications up the end of 1988. The score system developed by HANNE et al. allows causal differentiation between SO or uveitis of other genesis in the partner eye taking into account the prior history and findings in the EE and the occurrence of symptoms after the last accident/operation and findings in the SE. If the last eye is involved, the presence of SO should be assumed in every case where there are signs of intraocular inflammation in order to allow immediate commencement of anti-inflammatory therapy, the more so since it is known that corticosteroids and cytostatics (this also applies to cyclosporin A) can only arrest the immunopathologic processes in the initial phase of the disease. PMID- 2249918 TI - Cyclosporine-A in the treatment of serpiginous choroiditis. AB - Seven patients affected by bilateral inflammatory serpiginous choroiditis have been treated with Cyclosporine-A for 6-21 months. Nine out of the fourteen eyes showed a significant improvement in their visual acuity; five eyes did not change. Cyclosporine-A may, therefore, be considered effective in the treatment of this disease. Its usefulness seems to be greater when the serpiginous choroiditis is in its 'acute' stage; 'chronic' stages, however, also seem to improve under treatment. Its main indication is, in our opinion, the involvement of the macular region of the 'second' eye, when the 'first' eye is already damaged. We consider Cyclosporine-A, in these situations, to be a first choice treatment. PMID- 2249919 TI - Retinal vasculitis with multifocal retinochoroiditis. AB - We found a multifocal retinochoroiditis in 16 patients (13 female, 3 male). Patients also showed vitreous cells, in some cases pronounced retinal vasculitis, cystoid macular edema and papilledema. The patients ranged in age from 62 to 77 years. The anterior segment was involved in 13 cases. One patient demonstrated subretinal neovascularisation in both eyes. Fluorescein angiograms showed leakage from the retinal vessels, papilledema, macular edema and subretinal neovascularisation. A convincing classification of the described changes within any known disease entity was impossible. The findings most closely resembled a disease described by Dreyer and Gass in 1984 as 'multifocal choroiditis and panuveitis'. PMID- 2249921 TI - Advanced medical technology: finding the answers. AB - Nurses are increasingly questioning the decisions on the use and overuse of advanced medical technology, particularly when it concerns the elderly, psychiatric patients and children. Below, some of the troubling questions being asked and where nurses can find advice. PMID- 2249920 TI - Bilateral visual loss with eosinophilic infiltration in the bone marrow and the retina. AB - A young patient is described who presented with sudden visual loss in the left eye quickly followed by proliferative retinopathy with retinal detachment and thrombotic glaucoma. He developed similar initial symptoms in the right eye but has now made a complete recovery in that eye on systemic steroids, oral acyclovir, cyclosporin A and colchicine. Pathological examination of the left eye revealed inflammation in the ciliary body, retina and choroid with prominent eosinophils. The nature of the initial insult and the possible role of the eosinophils are discussed. PMID- 2249922 TI - Nurses' use of technology: an international concern. AB - The introduction of sophisticated health care technology does not guarantee quality patient care. Nor can all technology be just simply transferred to all countries. Below, the authors explain why. PMID- 2249923 TI - An economic model for nurse manpower planning in the Caribbean--Part 1: The issues. AB - Below is a noneconomist's view on economic issues impacting on nurse manpower development in the Commonwealth Caribbean. The issues however are of an international nature and are therefore pertinent to all those interested in nurse manpower development. The main objective is to present a model for economic analysis and planning. PMID- 2249924 TI - The brain drain as viewed by an exporting country. AB - Philippines, a country of 57 million, graduates a substantial number of nurses each year. In 1989 alone, approximately 7,350 new nurses were successfully registered with the Professional Regulation Commission, bringing the total to over 160,000 nurses registered since 1922. Paradoxically, the country suffers from a shortage of nurses in the midst of a bountiful supply of "human resources". Below are the consequences. PMID- 2249925 TI - Inspiring nursing students to mobilize communities in Nepal. AB - In 1987 nurse educators in Nepal implemented a revised certificate nursing curriculum oriented toward primary health care (PHC) and a bachelor of community health nursing (CHN) curriculum with emphasis on leadership in PHC. As both curricula included practical experience for nursing students in the community, the teachers had to strategize how to maximize both the students' learning and their contribution to community health. Below, how the educators encouraged reluctant students to not only participate in PHC activities but also change their negative attitudes about working in remote areas of Nepal. PMID- 2249926 TI - Glucose-induced dysmorphogenesis in the cultured rat conceptus: prevention by supplementation with myo-inositol. AB - Growth retardation and dysmorphogenesis in the rat conceptus are accompanied by diminished tissue myo-inositol following culture from day 9.5 to 11.5 of development in the presence of increased amounts of glucose. Reductions of myo inositol and increased malformations are not corrected by aldose reductase inhibitors. In contrast, supplementation of culture medium with myo-inositol (1.5 mg/ml) restores tissue myo-inositol content, lowers the incidence of dysmorphogenic embryos (from 51.1 to 28.6%, P less than 0.001) and reduces the incidence of neural tube defects to control levels (from 33.3 to 6%, P less than 0.001). These results suggest that myo-inositol depletion is involved in the mechanism of diabetic embryopathy. PMID- 2249927 TI - Dual challenge for glomerular damage in mice: uninephrectomy and repetitive pregnancies. AB - We examined the effects of unilateral nephrectomy (UNx) and repetitive pregnancies (RP) on glomerular damage and blood pressure in mice. Four groups of 10 female mice, 7 weeks old, underwent sham nephrectomy (SV) alone, sham nephrectomy and six pregnancies (SP), right nephrectomy alone (NV) and right nephrectomy followed by six repetitive pregnancies (NP). UNx resulted in a significant elevation of serum creatinine up to 11 weeks. In all animals pregnancy was associated with a temporary decrease in serum creatinine except at termination of the 6th pregnancy in group NP. UNx and RP did not result in an increase in protein excretion. UNx in both virgin and pregnant mice resulted in blood pressure elevation without any renal histological abnormalities by the end of the 6th pregnancy. We conclude that at least up to the end of the 3rd pregnancy, gestation was associated with augmentation in function of a single kidney. This effect was lost by the end of the 6th pregnancy. Multiple repetitive pregnancies in uninephrectomized animals entailed renal functional deterioration and a rise in blood pressure without renal histological abnormalities on light microscopy. PMID- 2249929 TI - Wartime neurosurgical experience in Lebanon, 1982-85. II: Closed craniocerebral injuries. AB - This report presents 64 patients who sustained military-related closed craniocerebral injuries during the Lebanon conflict of 1982-85, all of whom underwent CT scanning at the initial assessment. Of these, 59% required surgery for removal of hematomas, depressed fractures and for monitoring intracranial pressure, in addition to intensive care management of elevated intracranial pressure and associated insults. CT scan revealed brain concussion only in 23%, depressed fracture in 9%, brain contusion alone in 17%, extracerebral hematomas in 17%, intracerebral hematomas in 11%, and diffuse axonal injury in 22%. Overall mortality was 19%, and the outcome was good in 69%. Various factors affecting survival are discussed, and our findings are compared with those in the literature concerning closed head injuries among civilians. Attention is drawn to the high proportion of diffuse brain injury due to blasts caused by side mines. Despite continued efforts to hasten evacuation from the field and improve the management of warfare-related head trauma, the outcome is still far from satisfactory. PMID- 2249928 TI - Wartime neurosurgical experience in Lebanon, 1982-85. I: Penetrating craniocerebral injuries. AB - The present report analyzes 116 penetrating wounds of the brain sustained during warfare in Lebanon during 1982-85. Two basic mechanisms of injury were encountered: high-velocity bullets, and shrapnel and stones from explosive devices; and in one case a radio antenna penetrated the head through the orbit. The site of impact was at the convexity in 87% of cases and at the base of the skull in the remaining 13%. Surgery was performed in 83% of the patients: debridement-craniotomy in 73%, burr hole for intracranial pressure monitoring only in 6% and scalp closure only in 4%. The remaining 17% did not require surgery because of transbasal penetration without intracranial mass (10%) or due to moribundity. Indriven bone or foreign body fragments were removed only if readily accessible. The mortality rate was highest among patients with a Glasgow Coma Scale of less than or equal to 4 on arrival, after high-velocity bullet wounds, when the intracranial path was multilobar or transventricular, and when associated lesions were accompanied by shock. A follow-up study of the 49 Israeli survivors for almost 6 years revealed intracerebral-retained bone fragments in 48%, but these did not result in increased immediate or late complications (e.g., infection, epilepsy). These results support our conservative approach. Since all victims of penetrating head injuries were evacuated from Lebanon to Rambam Medical Center, Haifa, our report can serve as an estimation of the incidence of penetrating brain wounds and their burden on a front-line hospital. PMID- 2249930 TI - Effects of the Israel physicians' strike on the treatment and outcome of acute appendicitis in Jerusalem. AB - We sought to determine whether a prolonged physicians' strike causes changes in the delivery of health care and in the behavior of health care seekers? We compared appendectomy patients during the 1983 physicians' strike in Israel and during a control period in 1984, by analyzing the records of 171 patients in two Jerusalem hospitals. Patients had similar demographic characteristics and disease manifestation, but differed in their health care seeking behavior. The 1983 patients tended to postpone their first contact with the health system and frequently failed to present themselves for a follow-up visit after discharge. Control group patients were more likely to receive preoperative antibiotics and less likely to develop postoperative fever than the strike group patients. The findings confirmed that the differences between the strike and control groups were caused by administrative barriers resulting from the strike rather than by differences in actual medical treatment. PMID- 2249931 TI - Pyogenic liver abscess. AB - A retrospective study of 18 adults admitted to Meir General Hospital with pyogenic liver abscess during the years 1982-88 was conducted. Our most useful diagnostic tool was ultrasound, which was accurate in all 15 patients in whom it was performed. Only two patients presented with multiple abscesses. Increased alkaline phosphatase was the most predictive laboratory finding, seen in all but one patient. One person was treated conservatively by antibiotics only. In one patient the abscess drained spontaneously into the right thoracic cavity. Initial surgical drainage was done in nine patients and percutaneous catheter drainage in seven. Only one patient died, of septic shock, yielding a mortality rate of 5.5%. The treatment-related complication rate, observed in almost half of the patients, was high. All patients with such complications required repeated drainage, which was achieved surgically in all cases. PMID- 2249932 TI - Atypical presentation of Pneumocystis carinii pneumonia. AB - Pneumocystis carinii is a common cause of pneumonia in the immunosuppressed patient. Its radiological findings are usually homogeneous, diffuse and bilateral. We present a 27-year-old woman with non-Hodgkin's lymphoma presenting with unilateral right lung parenchymal infiltrates due to Pneumocystis carinii. In the immunosuppressed host, pneumonia limited to one lung should not preclude the diagnostic possibility of Pneumocystis carinii infection. PMID- 2249933 TI - Occurrence of cerebrohepatorenal (Zellweger) syndrome in the Karaite community in Israel: a genetic hypothesis. AB - Two infants with the cerebrohepatorenal (Zellweger) syndrome in Karaite families are described. This syndrome has an autosomal recessive mode of inheritance with an estimated incidence of between 1:25,000 and 1:100,000 live births. In addition to a previous report of the syndrome in a Karaite family, this report raises the possibility of a high incidence of Zellweger Syndrome among the Karaites in Israel. PMID- 2249934 TI - Is pregnancy deleterious in females with one kidney? PMID- 2249935 TI - Glucose and insulin responses to a glucose tolerance test in primary hyperparathyroidism before and after parathyroidectomy and during an acute calcium infusion. PMID- 2249936 TI - Central diabetes insipidus as presenting sign of metastatic clear-cell carcinoma. PMID- 2249937 TI - Metastatic carcinoma of the testis mimicking seminoma. PMID- 2249938 TI - Platelet secretory substances enhance in vitro plasma coagulation. PMID- 2249939 TI - Pentamidine-induced cardiotoxicity. PMID- 2249940 TI - Amelioration of severe torsion dystonia with perphenazine. PMID- 2249941 TI - Bone crisis in Gaucher disease--an update. PMID- 2249942 TI - [B-scan ultrasound in dermatology]. PMID- 2249943 TI - [Therapy of penis cancer: border lines between organ preservation and radical surgery]. PMID- 2249944 TI - [Dermatologic aspects of anorexia and bulimia nervosa]. AB - Anorexia and bulimia nervosa are common in western civilized countries. They are frequently associated with disorders of the skin. Up to now, no dermatological studies of large numbers of patients with eating disorders have been published. We examined 145 patients with eating disorders (65 anorexia nervosa, 80 bulimia nervosa) regarding skin alterations. Simultaneously we controlled the moisture content and the superficial lipids of the skin. Several symptoms relevant to dermatology were found. In detail we report on: xerosis, hair changes, nail disorders, pathognomonic hand lesions, sialadenosis, lesions of the oral mucosa and the teeth, peripheral oedema, acrocyanosis, petechiae and artefacts. PMID- 2249947 TI - [Postherpetic erythema exsudativum multiforme with concomitant exacerbation of psoriasis vulgaris]. AB - Herpes simplex virus (HSV) infection is a well-known trigger mechanism for both erythema multiforme (EM) and psoriasis. While HSV-related EM and psoriasis are not uncommon, simultaneous development of both disorders following HSV infection is relatively rare. We report on a patient who simultaneously developed both EM and a guttate psoriasis within 16 days of an HSV infection. The major differences in the pathophysiological mechanisms by which these dermatoses are triggered are discussed. PMID- 2249945 TI - [Acute febrile neutrophilic dermatosis (Sweet syndrome). Case report and immunohistologic study of neutrophil-associated proteolytic enzymes and their inhibitors]. AB - A 59-year-old female patient who developed fever, headache, arthralgia and painful, raised red cutaneous plaques located predominantly on the upper trunk is presented. On the basis of the clinical and histological findings acute febrile neutrophilic dermatosis (Sweet's syndrome) was diagnosed. In affected skin we applied immunohistochemical methods to examine the topographical organization of neutrophil-associated proteinase/proteinase inhibitor systems, i.e. the PMN elastase/alpha 1-proteinase inhibitor and the cathepsin G/alpha 1 antichymotrypsin systems. Cathepsin G, PMN-elastase and alpha 1-antichymotrypsin were found in association with the polymorphonuclear infiltrating cells, whereas alpha 1-proteinase inhibitor was localized exclusively in the subepidermal oedema. In conclusion, our immunohistological findings support the view that free PMN-elastase is involved in the pathogenesis of cutaneous lesions in Sweet's syndrome. PMID- 2249946 TI - [Squamous cell cancers in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa]. AB - Recessive dystrophic epidermolysis bullosa is one of the most severe hereditary mechano-bullous diseases, characterized by scarring blister formation, nail dystrophy and onycholysis, cutaneous contractures, synechiae, mutilations of the hands and feet and oesophageal stenosis. With increasing age the patients may develop multiple, fast-growing and early-metastasizing squamous cell carcinomas. When epidermolysis is present, precise determination of which of the various forms is concerned is necessary soon after birth, to make it possible to advise parents about the prognosis of the disease and the likelihood of its occurrence in further children. In pregnancies at risk of severe epidermolysis bullosa a prenatal diagnosis should be performed. We present two siblings with recessive dystrophic epidermolysis bullosa, each of whom developed two squamous cell carcinomas. PMID- 2249948 TI - [Diagnostic criteria in epiluminescence microscopy. Consensus meeting of the professional committee of analytic morphology of the Society of Dermatologic Research, 17 November 1989 in Hamburg]. PMID- 2249949 TI - [Presentation of patients with skin diseases in the early Renaissance:Fraciscus Petrarca "Von der Artzney bayder Gluck"]. PMID- 2249950 TI - Characterization of skin-infiltrating T lymphocytes during acute graft-versus host disease. AB - A panel of 34 clones was established from a cell line derived from the skin biopsy of a patient (genotype: A1, A2, B7, B8, DR3, DR6) undergoing acute graft versus-host disease after semiallogeneic bone marrow transplantation with his mother's bone marrow (genotype: A1, A1, B7, B8, DR3, DR6). The T-cell line obtained presented the following phenotype: CD3+, CD4+, CD8-, CD16-, WT31+, T cell receptor delta 1-, 4B4+, 2H4-, CD25+, DR+. This CD4+ T-cell line was poorly cytotoxic against the target cells tested, including the mother's phytohemagglutinin blasts as a negative control (autologous T cells), the father's phytohemagglutinin blasts bearing the mismatch haplotype, K562, U937, SVK14 (a keratinocyte cell line), and a panel of B-lymphoblastoid cell lines bearing HLA-A2, the known mismatch antigen. All but 1 of the 34 clones obtained were of CD4+ phenotype, and none was CD16+. Only the sole CD8+ clone showed significant cytotoxicity against the father's phytohemagglutinin blast; however, this cytotoxic activity was associated with the highest score for nonspecific killing against both K562 and U937. This work demonstrates the feasibility of obtaining a large panel of clones from a graft-versus-host disease target organ to constitute the basic cellular material for in vitro study of the graft-versus host process. PMID- 2249951 TI - Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. AB - The data presented here demonstrate that the HLA-G class I gene is unique among the members of the human class I gene family in that its expression is restricted to extraembryonic tissues during gestation. Furthermore, the pattern of HLA-G expression in these tissues changes as gestation proceeds. During first trimester HLA-G is expressed within the placenta and not within the extravillous membrane. At term, the pattern of the HLA-G expression is reversed, extravillous membrane expresses HLA-G while placenta does not. Another non-HLA-A, -B, -C class I gene, HLA-E, is also expressed by extraembryonic tissues. Unlike HLA-G, HLA-E is expressed by both placenta and extravillous membrane at first trimester and at term. These results raise the intriguing possibility that the HLA-G-encoded molecule has a role in embryonic development and/or the fetal-maternal immune response. PMID- 2249952 TI - Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. AB - We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, -B, and -D antigens of the haplotype not shared; 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurrence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts occurrence of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21-0.57, p less than 0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52-2.50, p less than 0.0001; (3) patient age, relative risk = 1.23 per decade; 95% confidence interval, 1.05-1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, the rate of leukemic relapse was 22% in 61 recipients of "one-locus" (A, B, or D) incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of "one-locus"-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients. PMID- 2249953 TI - Superposition of hydrodynamic forces on a hair bundle. AB - Vertebrates sense sound, orientation, and motion by means of bundles of microscopic sensory hairs that protrude from the surfaces of receptor (hair) cells. To determine the effects of the sensory epithelium, tectorial structures, and fluids on the motions of hair bundles, we examine a class of mathematical models in which hair-cell organs are represented as a system of rigid mechanical structures surrounded by fluid. The epithelium and tectorial structures are represented by rigid basal and tectorial plates, respectively; the hair bundle by a rigid body hinged to the basal plate. When the displacements of these structures are small, the equations of motion for the fluid are predominately linear. Therefore, both the fluid velocity and the force of fluid origin on the body can be expressed as a sum of components; each component results from motion of a single structure while all others are stationary. This analysis leads to a network description of the motion of the rigid body in which hydrodynamic forces are segregated from mechanical forces. The separation of hydrodynamics and mechanics not only clarifies the effects of fluids on motion but also minimizes the number of hydrodynamic computations needed to analyze models of hair-bundle motion. PMID- 2249954 TI - On the pathophysiology of tinnitus; a review and a peripheral model. AB - In this paper I investigate the consequences of the assumption that tinnitus is the result of correlated neural activity in auditory nerve fibers under 'no sound' conditions. Two possible pathological conditions capable of causing this correlation are ephaptic excitation of one nerve fiber by neighboring nerve fibers and synchronization of the various synapses in individual hair cells. The first condition is likely to be found in cases suffering from acoustic neuroma where the myelin sheath of the auditory neurons is damaged. The second condition is attributed to a spontaneous excess influx of K+ or Ca2(+)-ions into the hair cell resulting in transient hair cell depolarizations causing synchronous transmitter release at all hair cell synapses. This condition is postulated in noise trauma and ototoxic drug damage of the inner hair cell membrane. The model produces the excess of short interspike intervals found in auditory nerve fiber recordings in animal models of tinnitus as well as the theoretically required correlation in the activity of neighboring neurons. PMID- 2249955 TI - Recovery from short-term adaptation in single neurons in the cochlear nucleus. AB - Recovery from short-term adaptation was measured in single neurons in the cochlear nucleus using a forward masking stimulus paradigm. The response to a short-duration, low-level probe tone at a unit's characteristic frequency (CF) was measured before and after presentation of a masker tone at the unit's CF. The degree of adaptation was defined as the ratio of firing to the probe in the adapted and unadapted conditions. The level of the masker and time difference between the masker offset and probe onset ('DT') were varied. As DT increased, the response to the probe increased in most Primarylike, Primarylike-notch, and Chopper units. Recovery was approximately linear in log time for most of these units. However, approximately half the Pauser/Buildup and On units showed very different recovery patterns, ranging from no adaptation to very non-linear recovery patterns. The results suggest that little alteration in the recovery process occurs between the auditory nerve and Primarylike, Primarylike-notch, and Chopper units, but that significant changes in the recovery process occur in Pauser-Buildup and On units. PMID- 2249956 TI - Toadfish saccular hair cell bundle has a preferred orientation in the otolithic membrane. AB - The macula of the saccule of the toadfish, Opsanus tau, is covered by an otolithic membrane containing sockets into which the stereocilia and kinocilia of the hair cells project. We have found that the hair cell bundle has a distinct eccentric orientation within this space of the otolithic socket. Although the sockets of the otolithic membrane are irregular in shape, all kinocilia are located closet to the same border of the sockets. Since the socket is a fluid or gel filled space through which the hair cell bundle moves, this orientation may have some significance for transduction since it leaves a larger space in the on direction for stereociliary movement. PMID- 2249957 TI - Eighth nerve contributions to cat auditory brainstem responses (ABR). AB - There is a temporal correspondence between some of the early components of the auditory brainstem potentials in cat and the negative peak of the triphasic nerve action potential recorded from selected points along the VIII cranial nerve. The intracranial portion of the VIII nerve in cat has a conduction velocity of 10 meters/s. The initial peak of the ABR, P1a, is coincident with the negative portion of the triphasic VIII nerve action potential within the cochlea as recorded from the round window. The next peak (P1b) of the ABR occurs 400 microseconds later and is coincident with the negative portion of the triphasic VIII nerve action potential recorded from just within the lateral border of the cochlear nucleus. These results are similar to studies of the human ABR that show waves I and II are correlated with activity of the VIII nerve. It is likely that waves P1a and P1b in cat are homologous to waves I and II in human. In cat, these first two peaks of the ABR can be distinguished in vertex to neck recordings but not in vertex to ipsilateral mastoid derivations. PMID- 2249958 TI - Ultrastructural observations on regenerating hair cells in the chick basilar papilla. AB - This experiment was designed to investigate cellular and subcellular maturational changes in regenerated immature sensory cells and support cells of the chick basilar papilla following gentamycin treatment. Scanning and transmission electron microscopy were used. The experimental animals received one subcutaneous injection of gentamycin sulfate daily (50 mg/kg) for five or 10 days. The animals receiving five days of injection were sacrificed the following day. The remaining animals were allowed to survive either seven or 28 days before sacrifice and preparation for electron microscopy. The initial lesion consisted of total degeneration of hair cells within 500 microns of the proximal tip providing the opportunity to study a 'pure' population of regenerating sensory cells. Sensory cell regeneration could be identified by one day after terminating gentamycin treatment. Early in development sensory cell precursors were morphologically very similar to supporting cells. A density gradient, based on cytoplasmic staining characteristics, was established which increased from cells displaying low density at the base of the supporting cell layer to high density cells at the luminal surface. These changes in density were equated to increase in number of and types of cytoplasmic organelles. In contrast to the empty appearing cytoplasm of the support cell, the cytoplasm of the hair cell precursor contained numerous mitochondria, clusters of ribosomes, and vesicles. As the cell approached the surface, mitochondria became more numerous as did smooth and coarse endoplasmic reticulum and Golgi apparatus. This gradient suggested that determination of the cellular phenotype occurred at the level of the basal membrane followed by migration to the surface, during which time differentiation was characterized by an increase in number and complexity of cellular organelles. Luminal surface modifications occurred as soon as the cell erupted. The development of stereocilia, rootlet, cuticular plate and cellular polarization followed the normal embryogenetic pattern. At 28 days, stereocilia organization was still incomplete as was the orientation of the bundle. To the extent that proper orientation of hair cells or bundles is necessary for normal transduction, mature function at 28 days would not be anticipated. Innervation of the presumptive hair cell precursors could be observed one day after treatment, early in the course of hair cell differentiation. Synaptogenesis followed the normal embryogenetic sequence; however, afferent and efferent nerve terminals remained immature appearing at 28 days. This observation may have physiological implications manifested by delay of hearing PMID- 2249959 TI - Hydrodynamic forces on hair bundles at low frequencies. AB - We have analyzed a model for the motion of hair bundles of hair cells at low frequencies. In the model, hair-cell organs are represented as a system of rigid mechanical structures surrounded by fluid. A rigid body, that represents a hair bundle, is hinged to a vibrating plate that represents the sensory epithelium. These structures are surmounted by a second vibrating plate that represents a tectorial structure. The analysis shows that both viscous and inertial properties of the fluid are important even at asymptotically low frequencies. The relative importance of these properties depends critically on the presence and mode of motion of the tectorial plate. As a result, the angular displacement of the body at low frequencies can be proportional to basal plate displacement, velocity, acceleration, or to no simple integral of its motion; the functional relation depends upon the disposition of the tectorial plate. PMID- 2249960 TI - Hydrodynamic forces on hair bundles at high frequencies. AB - We have analyzed a model for the motion of hair bundles of hair cells at high frequencies. In the model, hair-cell organs are represented as a system of rigid mechanical structures surrounded by fluid. A rigid body, that represents a hair bundle, is hinged to a vibrating plate that represents the sensory epithelium. These structures are surmounted by a second vibrating plate that represents a tectorial structure. The analysis shows that at high frequencies, fluid forces cause the rigid body to move as though it were attached to the plates with a system of levers. As a result, the angular displacement of the rigid body is proportional to the displacements of the plates even when there are no mechanical attachments of the body to the tectorial plate. This result is independent of both the size and the shape of the rigid body and independent of the presence and proximity of the tectorial plate, although the constant of proportionality depends upon these factors. Therefore, the mechanical stimulation of hair cells may be particularly simple at high frequencies where the structural differences in hair bundles and tectorial attachments--that have been shown to be important at low frequencies--play a less important role. PMID- 2249961 TI - Hydrodynamic analysis of a two-dimensional model for micromechanical resonance of free-standing hair bundles. AB - To investigate the role of inner ear fluids and structures on mechanical stimulation of the hair bundles of hair cells, we analyzed a two-dimensional structure that consists of: a rectangular flap (which represents a hair bundle) attached to a flat basal plate (which represents the surface of the epithelium that contains the hair cells) with a spring-loaded hinge (that represents the compliant attachment of a hair bundle to the hair cell body) and surrounded by a viscous fluid (that represents endolymph). We computed the fluid velocity as well as the forces on and motion of the flap in response to sinusoidal vibration of the plate by numerical integration of the hydrodynamic equations, and--at asymptotically low and high frequencies--by analytic methods. The results suggest that: (1) the surface of the sensory epithelium, from which hair bundles project into fluid, plays an important part in the production of fluid forces on hair bundles; (2) both fluid inertia and viscosity play a key role in hair bundle mechanics; (3) passive mechanical resonances are likely to contribute to both frequency selectivity and frequency-to-place coding in the inner ear. PMID- 2249963 TI - Suppression and excitation in auditory nerve fibers of the goldfish, Carassius auratus. AB - The suppression of background spike activity in the absence of deliberate acoustic stimulation occurs in fibers of the goldfish saccular nerve tuned in the region of 250 Hz. Suppression is most robust in the frequency range between 450 and 1050 Hz, the range of CF for the mid- and high-frequency saccular fibers. Suppression of background activity tends to occur following the suppressor tone offset ('off-suppression'), even though the spike response during the suppressor is below the background rate. This suggests that the suppressor tone is excitatory at the level of the hair cells and their synapses onto saccular afferents. Tones at the low- frequency edge of the suppression region may show net excitation at low intensity levels, and net suppression at higher levels. This suggests that the spike response observed is the result of the relative strengths of excitatory and suppressive effects which operate simultaneously. The magnitude and frequency of best suppression tends to increase with stimulus intensity. A suppressing tone produces transient excitation at onset. In fibers with high levels of spontaneous activity, a spike response 'rebound' often occurs 20 to 50 ms following the suppressing tone offset. These 'on' and 'off' effects are not due to energy 'splatter' in the stimulus domain. Suppression by tones can also be observed in non-spontaneous fibers when the background spike activity is evoked by noise. In these cases, however, off-suppression following a suppressed response and the 'rebound' seldom occurs. Possible sites of suppression are the hair cells and their synapses, the spike-initiation zones of the saccular afferents, and efferent inhibition. The most likely site seems to be the spike initiation zones of saccular afferents. An important consequence of suppression for hearing is the sharpening of frequency response areas for low frequency fibers, and the partial preservation of frequency analysis in saccular fibers stimulated well above threshold. PMID- 2249962 TI - Morphological correlates of aging in the chinchilla cochlea. AB - The inner ears from 80 chinchillas ranging in age from premature to 19.2 years were examined as plastic-embedded flat preparations to determine the morphological changes associated with aging. Three of the four forms of human presbycusis defined by Schuknecht were found in the chinchillas. All animals had losses of sensory cells or sensory presbycusis. Inner (IHCs) and outer hair cells (OHCs) degenerated at a rate of about 0.29% and 1.0% per year, respectively. Age related degeneration of inner (IPs) and outer pillars (OPs) occurred at a much slower rate. In four animals (5%) the dendritic processes of some of the spiral ganglion cells had degenerated in areas where the loss of sensory cells was minimal. This pathological change is likely equivalent to neural presbycusis. Six animals (7.5%) had regions of degeneration of the stria vascularis or strial presbycusis. The other common finding in the aging cochleas was the presence of lipofuscin or age pigment. Lipofuscin deposits were found to accumulate in the subcuticular region of OHCs, IPs and OPs, near the endolymphatic surfaces of many of the supporting cells and in the epithelial cells of Reissner's membrane. The IHCs accumulated much less lipofuscin. The morphological changes seen in the ears of aging chinchillas were qualitatively similar to those seen in the temporal bones of aging humans although the magnitude of the changes was considerably less. These results suggest that some of the damage found in aging human cochleas may be due to aging plus exposure to one or more ototraumatic agents. PMID- 2249964 TI - An analysis of and intervention in the sexual transmission of disease. AB - Sexually transmitted diseases are a serious threat to the public health. Indeed, when an individual seeks medical treatment for a sexually transmitted disease, health authorities frequently attempt to identify, procure, and treat that individual's sexual contact(s). We conducted a comparative analysis of three alternative approaches to tracing the sexual partners of individuals diagnosed as having a sexually transmitted disease. The first approach involved counseling individuals (n = 27) infected with either gonorrhea or nongonococcal urethritis and exhorting them to procure their sexual partners for treatment. In addition to counseling, the second and third approaches involved distributing "occasion cards" for patients to use when informing sexual contacts of the need for treatment. Moreover, in the second approach, the counselor (a nurse or physician) informed infected patients (n = 19) that they and their partners could waive the $3 clinic fee contingent upon the partners seeking treatment within 1 week. In the third approach, the counselor asked infected persons (n = 19) to accept a follow-up telephone contact if their sexual partners failed to seek treatment within 1 week. The third approach was most effective. Ninety percent of the partners identified through this approach sought treatment, versus only about 60% of the partners in the other two conditions. The third approach was also the least expensive, costing about $2.95 to procure each partner for treatment. PMID- 2249965 TI - Using parents as therapists to evaluate appropriate behavior of their children: application to a tertiary diagnostic clinic. AB - We conducted a preliminary analysis of maintaining variables for children with conduct disorders in an outpatient clinic. Eight children of normal intelligence between the ages of 4 and 9 years were evaluated during 90-min sessions. The children's parents conducted the assessments by varying task demands (easy and difficult) and parental attention (attention and no attention) within a multielement design. The assessment focused on appropriate child behavior and was conducted to formulate hypotheses regarding maintaining contingencies. Results demonstrated that the children's appropriate behavior varied across assessment conditions and, for 7 of the 8 children, occurred at a higher rate during one condition than during other conditions. In addition, treatment integrity data demonstrated that parents were able to implement the procedures as intended. The recommended treatments were rated as being both effective and acceptable to parents for up to 6 months following the evaluation. Our results extend previous studies of functional analytic procedures conducted by trained experimenters with severely handicapped children in more controlled settings. PMID- 2249967 TI - Effects of collateral peer supportive behaviors within the classwide peer tutoring program. AB - A classwide peer tutoring procedure was implemented in an urban elementary school classroom to improve students' spelling performance. Three students combined untrained or collateral tutoring behaviors with the core behaviors initially taught. To explore the function of these natural and spontaneous behaviors, a multielement single-subject experiment with replications was conducted. Results indicated that the additional tutoring behaviors increased (a) the academic response frequencies of 3 tutees and (b) the weekly spelling achievement of 1 target tutee. The remaining class members were successfully taught and continued to use these behaviors over the final 3 weeks of the school year. These findings are discussed with regard to academic instruction, natural communities of peer reinforcement, and the social validation of intervention procedures. PMID- 2249966 TI - Teaching youths with autism to offer assistance. AB - Three adolescent boys with autism were taught to offer assistance to a person stating inability to complete a task. The study used a multiple baseline across the 3 youths and a multiple baseline across three tasks for each student. Both designs provided clear support for the ability of the youths to discriminate those settings in which offers of assistance were desired. All 3 participants showed relatively rapid acquisition of responding. Generalization was assessed to a new person in the training setting, to a familiar person in a new room at the center, to the mother in the youth's home, and to three novel tasks. Generalization to a new person in the familiar setting was most likely to occur, with very high levels of responding for all 3 youths. Generalization to the other conditions varied across youths, although all 3 boys showed some transfer of skills to all conditions. PMID- 2249970 TI - Reducing disruptive behaviors of elementary physical education students with sit and watch. AB - This study reduced the disruptive behaviors of students in two elementary physical education classes: a regular fourth-grade class comprised of 30 students and an alternative education class containing 14 fourth- and fifth-grade boys with severe behavior problems. Using a multiple baseline design, we introduced a modified time-out procedure called "Sit and Watch." The procedure reduced the frequency of disruptive behaviors by 95%. Sit and Watch proved to be socially acceptable to parents, school personnel, and the physical education teacher. PMID- 2249968 TI - The representativeness of observational samples of different durations. AB - The representativeness of behavioral observation samples with durations of less than the whole time of interest was investigated. A real-time recording system was developed to quantify the behavior of 5 profoundly mentally retarded physically handicapped adult students in an institutional training setting. Behavior was observed using six mutually exclusive and exhaustive categories during 2.5-hr observation sessions. Sample observation sessions with durations ranging from 15 to 135 min were computer simulated from the whole-session (150 min) records. It was found that the representativeness of these samples, when compared to whole-session records, was a function of the relative duration of the behavioral categories and of sample duration. The occurrence of relatively high duration behaviors (lasting for more than 50% of the session) was estimated to within 20% error by samples of less than 60 min, but low-duration behaviors (1 to 3% of the session) were inadequately quantified even from 135-min samples. Increasing irregularity of bouts of behavior in the low-duration behaviors is suggested as the cause of the functions obtained. Implications of the findings for applied behavior analysis are discussed, with the recommendation that the adequacy of observational session durations be empirically assessed routinely. PMID- 2249971 TI - Artifactual effects of sensory-integrative therapy on self-injurious behavior. AB - Three individuals who exhibited self-injurious behavior (SIB) were exposed to sensory-integrative therapy. Prior to treatment, a functional analysis baseline was conducted to identify the motivational features of their SIB. One subject's SIB appeared to be an attention-getting response (maintained by positive reinforcement), which varied subsequently as a function of attention being either withheld or provided noncontingently during sensory-integration sessions. The 2nd subject displayed a pattern of responding suggestive of stereotypic SIB (maintained by automatic reinforcement), which paradoxically increased during sensory-integration sessions. The 3rd subject's SIB appeared to function as an escape response (maintained by negative reinforcement), and his behavior during sensory-integration sessions was similar to that observed during baseline sessions in which demands were not present. The SIB of all 3 subjects later was reduced when behavior interventions were applied. The data presented raise questions about the active components of sensory-integrative therapy and the functional types of SIB for which it might be appropriate. PMID- 2249969 TI - Applications of a sequential alternating treatment design. AB - We propose the use of a combined version of the alternating treatments and multiple baseline designs in situations in which a traditional baseline (no treatment) condition either does not provide an adequate contrast condition or is not feasible or practical due to clinical constraints. We refer to this design as a sequential alternating treatments design because two treatments are initially implemented in a random or counterbalanced fashion and are followed by a sequential change in one or both treatments across settings, subjects, or tasks. The effects of the independent variables are assessed first by analyzing the two series of data points representing the different treatments (relative effects) and then by assessing changes in one or both series, as application of the alternative treatment is introduced sequentially. The sequential application of treatment provides an analysis of control in the same manner as the multiple baseline design; the initial alternating treatments phase provides a contrast condition in much the same manner as a baseline condition. Applications of this design to the assessment of peer training and self-injurious behavior are described. PMID- 2249972 TI - Improved curveball hitting through the enhancement of visual cues. AB - This study investigated the effectiveness of using visual cues to highlight the seams of baseballs to improve the hitting of curveballs. Five undergraduate varsity baseball team candidates served as subjects. Behavior change was assessed through an alternating treatments design involving unmarked balls and two treatment conditions that included baseballs with 1/4-in. and 1/8-in. orange stripes marking the seams of the baseballs. Results indicated that subjects hit a greater percentage of marked than unmarked balls. These results suggest that the addition of visual cues may be a significant and beneficial technique to enhance hitting performance. Further research is suggested regarding the training procedures, effect of feedback, rate of fading cues, generalization to live pitching, and generalization to other types of pitches. PMID- 2249973 TI - Mothers as effective therapists for autistic children's phobias. AB - Two autistic children were treated for specific fears. A three-component participant modeling procedure was implemented within a multiple baseline design across subjects. Children were exposed gradually to fearful situations, with mothers serving as therapists and reinforcers. Dependent measures were (a) number of approach steps completed, (b) frequency of verbalizations and vocalizations of fear, and (c) overall appearance of fear. Following treatment, the children functioned effectively in previously fearful situations without verbalizations or appearance of fear. Five-month and 1-year follow-up assessments with 1 child showed maintenance of treatment effects. PMID- 2249974 TI - Long-term follow-up of echolalia and question answering. AB - A long-term follow-up of echolalia and correct question answering was conducted for 6 subjects from three previously published studies. The follow-up periods ranged from 26 to 57 months. In a training site follow-up, subjects were exposed to baseline/posttraining conditions in which the original trainer and/or a novel person(s) presented trained and untrained questions. Four subjects displayed echolalia below baseline levels, and another did so in some assessments. Overall, echolalia was lower than in baseline in 80.6% of the follow-ups. Five subjects displayed correct responding above baseline levels. No clear differences were noted in correct responding or echolalia between the trainer and novel-person presentations or between trained and untrained questions. In a follow-up in a natural environment conducted by a novel person, lower than baseline levels of echolalia were displayed by 3 subjects; 2 subjects displayed lower than baseline levels in some assessments. Two subjects consistently displayed correct responding above baseline, and 3 did so occasionally. Issues related to the study of maintenance are discussed. PMID- 2249976 TI - On the nature of the uncoupling effect of fatty acids. AB - The effect of palmitic acid on the electrical potential differences delta psi across the inner mitochondrial membrane appears to depend on the medium in which mitochondria are incubated. In medium A (cf. Luvisetto et al. (1987), Biochemistry, 26, 7332-7338) delta psi decreases much more than in medium B (cf. Rottenberg and Hashimoto (1986), Biochemistry, 25, 1747-1755) at concentrations of fatty acid which equally stimulate the rate of respiration in state 4. Valinomycin and NaCl were both present in medium B and absent in medium A. However, in both media the pattern of the P/O ratio as a function of antimycin in the presence of a constant amount of palmitic acid or of FCCP shows similar behaviour. We conclude that in both media palmitic acid increases the membrane conductance to protons, but for unclear reasons the delta psi assay fails to measure the decline of delta psi in medium B. However, the increase in membrane conductance induced by palmitic acid does not quantitatively account for the stimulation of the rate of respiration. PMID- 2249975 TI - Plasma membrane dehydrogenases in rat brain synaptic membranes. Multiplicity and subunit composition. AB - Plasma membrane redox enzymes have been investigated in synaptic membranes from rat brain nerve terminals. UV-Vis spectra of intact synaptic plasma membranes are presented and the presence of a b-type cytochrome, detectable at 77 degrees K and sensitive to NADH or NADPH, is shown. The molecular characterization of rat synaptic NADH-dehydrogenases was further performed on solubilized enzymes using a recently developed nondissociating polyacrylamide gel electrophoresis technique. Synaptic plasma membranes were solubilized with 1% sodium cholate or Triton X-114 and centrifuged. The supernatant retained over 60% of the NADH-dehydrogenase activity, tested with either DCIP2 or ferricyanide as substrates, together with NADH. Both enzyme activities were insensitive toward rotenone. This extraction procedure also solubilized about 50% of the proteins. When submitted to polyacrylamide gel electrophoresis under nondenaturing conditions and stained for NADH-dehydrogenase activity, five bands of different mobilities were detected. The multiple NADH-dehydrogenases of synaptic plasma membranes were investigated by means of band excision and the five excised bands each submitted to amino acid analysis and to 2-D electrophoresis. The subunit composition of each band was then deduced, together with the molecular weight and pI of each respective subunit. NADH-dehydrogenases have also been purified by means of FPLC on Mono-P (chromatofocusing) followed by gel filtration on Superose 12. NADH-Dehydrogenase IV and V could be purified in their active forms by this approach. PMID- 2249977 TI - Effects of plasma membrane oxidoreductases on Ca2+ mobilization and protein phosphorylation in rat brain synaptosomes. AB - We have investigated the possible role of plasma membrane oxidoreductases in the Ca2+ export mechanisms in rat brain synaptic membranes. Ca2+ efflux in nerve terminals is controlled both by a high-affinity/low capacity Mg-dependent ATP stimulated Ca2+ pump and by a low affinity/high capacity ATP-independent Na(+) Ca2+ exchanger. Both Ca2+ efflux mechanisms were strongly inhibited by pyridine nucleotides, in the order NADP greater than NAD greater than NADPH greater than NADH with IC50 values of ca. 10 mM for NADP and ca. 3 mM for the other agents in the case of the ATP-driven Ca2+ pump and with IC50 values between 8 and 10 mM for the Na(+)-Ca2+ exchanger. Oxidizing agents such as DCIP3 and ferricyanide inhibited the ATP-driven Ca2+ efflux mechanism but not the Na(+)-Ca2+ exchanger. In addition, full activation of plasma membrane oxidoreductases requires both an acceptor and an electron donor; therefore the combined effects of both substrates added together were also studied. When plasma membrane oxidoreductases of the synaptic plasma membrane were activated in the presence of both NADH (or NADPH) and DCIP or ferricyanide, the inhibition of the ATP-driven Ca2+ pump was optimal; by contrast, the pyridine nucleotide-mediated inhibition of the Na(+)-Ca2+ exchanger was partially released when both substrates of the plasma membrane oxidoreductases were present together. Furthermore, the activation of plasma membrane oxidoreductases also strongly inhibited intracellular protein phosphorylation in intact synaptosomes, mediated by either cAMP-dependent protein kinase, Ca2+ calmodulin-dependent protein kinases, or protein kinase C. PMID- 2249978 TI - A characterization of cuprizone-induced giant mouse liver mitochondria. AB - Cuprizone affects the liver of treated mice in a random manner, causing no appreciable change in some cases and inducing the formation of megamitochondria with altered properties in others. Lack of a full appreciation of this variability may be at the origin of some discrepancies in published work dealing with the properties of cuprizone mouse liver mitochondria (CMLM). CMLM from fully affected livers were remarkably labile and difficult to isolate in a coupled state by homogenization and centrifugation techniques. The integral respiratory chain proteins of CMLM were functionally normal, with the exception of succinic dehydrogenase which showed considerable inhibition. Coupled morphological and functional analysis provided evidence that these properties were independent of CMLM size, a matter which had remained doubtful thus far and bears on the validity of literature reports. PMID- 2249981 TI - The enzymes of detoxication. PMID- 2249982 TI - Anionic site interactions in human butyrylcholinesterase disrupted by two single point mutations. AB - Structure-function relationships of recombinant human butyrylcholinesterase (CHE) variants were investigated by Xenopus oocyte microinjection. A Ser-425 to Pro-425 mutation failed to modify ligand binding properties. In contrast, Asp-70 to Gly 70 substitution significantly reduced CHE binding capacity for succinylcholine and specific inhibitors, demonstrating Asp-70 as a key anionic site component for certain ligands. Furthermore, the presence of both mutations rendered CHE totally resistant to succinylcholine and dibucaine inhibition, while all mutant proteins bound butyrylthiocholine, benzoylcholine, and propionylcholine normally. These findings imply structural interactions between the conserved Asp-70 and Ser-425 regions in cholinesterases and suggest the contribution of additional electronegative amino acids to anionic site binding. PMID- 2249980 TI - The use of amphipathic maleimides to study membrane-associated proteins. AB - A series of amphiphilic polymethlyenecarboxymaleimides has been synthesized for use as sulfhydryl reagents applicable to membrane proteins. Physical properties of the compounds which are relevant to their proposed mode of action have been determined. By comparing rates of reaction in aqueous and aprotic solvents, the compounds have been shown to react exclusively with the thiolate ion. The effects of the reagents on three membrane-associated proteins are reported, and in two cases a comparative study has been made of the effects on the proteins in the absence of membranes. A mechanism is proposed whereby the reagents are anchored at the lipid/water interface by the negatively charged carboxyl group, thus sitting the reactive maleimide in a plane whose depth is defined by the length of the reagent. Supporting evidence for this model is provided by the inability of the reagents to traverse membranes, and variation of their inhibitory potency with chain length when the proteins are embedded in the membrane, but not when extracted into solution. As examples of general use of the reagents to probe sulfhydryl groups in membrane proteins, the reagents have been used to (a) determine the depths in the membrane at which two populations of sulfhydryl groups occur in the mitochondrial phosphate transporter; (b) locate a single sulfhydryl associated with the active site of D-beta-hydroxybutyrate dehydrogenase in the inner mitochondrial membrane; (c) examine sulfhydryl groups in the D-3-glyceraldehyde phosphate dehydrogenase associated with the human red blood cell membrane. PMID- 2249979 TI - Dicyclohexylcarbodiimide as inducer of mitochondrial Ca2+ release. AB - The effect of the alkylating reagent dicyclohexylcarbodiimide (DCCD) on mitochondrial Ca2+ content was studied. The results obtained indicate that DCCD at a concentration of 100 microM induces mitochondrial Ca2+ efflux. This reaction is accompanied by an increasing energy drain on the system, stimulation of oxygen consumption, and mitochondrial swelling. These DCCD effects can be partially suppressed by supplementing the incubation medium with 1 mM phosphate. By electrophoretic analysis on polyacrylamide-sodium dodecyl sulfate, it was found that DCCD binds to a membrane component with an Mr of 20 to 29 kDa. PMID- 2249983 TI - Structural organization of the human S-antigen gene. cDNA, amino acid, intron, exon, promoter, in vitro transcription, retina, and pineal gland. AB - S-Antigen (S-Ag) is a major soluble photoreceptor protein involved in the visual transduction cascade. Several S-Ag cDNAs and a gene coding for human S-Ag were isolated from cDNA and gene libraries. The gene sequences of the coding, noncoding, and 5'-flanking regions of the gene were determined. The S-Ag gene was approximately 50 kbp (kilobase pairs) in length and contained 16 exons and 15 introns. The length of most exons was less than 100 base pairs (bp) and the smallest one was only 10 bp. In contrast, the length of most introns was larger than 2 kbp, and the gene comprised 97% intron and 3% exon. The splice sites for donor and acceptor were in good agreement with the GT/AG rule. The S-Ag protein of 403 amino acid residues was translated from a mRNA of 1.9 kbp, and the mRNA was transcribed from a gene of 50 kbp. The 5'-flanking region of the gene, approximately 1.1 kbp long, had no known regulatory elements for transcription such as TATA, GC, and CCAAT boxes. Interestingly, the 5'-flanking region had promoter activity in an in vitro transcription assay using a nuclear extract of rat brain. A major transcription start site was found at 387 bp upstream from the translation start site ATG. Our results indicate that the sequence of S-Ag promoter differs from other known promoters and may, perhaps, be specific for photoreceptor rod cells and pinealocytes. PMID- 2249985 TI - Differential recognition of core and terminal portions of oligosaccharide ligands by carbohydrate-recognition domains of two mannose-binding proteins. AB - Two different mannose-binding proteins (MBP-A and MBP-C), which show 56% sequence identity, are present in rat serum and liver. It has previously been shown that MBP-A binds to a range of monosaccharide-bovine serum albumin conjugates, and that, among oligosaccharide ligands tested, preferential binding is to terminal nonreducing N-acetylglucosamine residues of complex type N-linked oligosaccharides. In order to compare the binding specificity of MBP-C, an expression system has been developed for production of a fragment of this protein which contains the COOH-terminal carbohydrate-recognition domain. After radioiodination, the domain has been used to probe natural glycoproteins, neoglycoproteins, and neoglycolipids. Like MBP-A, MBP-C binds several different monosaccharides conjugated to bovine serum albumin, including mannose, fucose, and N-acetylglucosamine, although binding to the last of these is relatively weaker than observed for MBP-A. The results of binding to natural glycoproteins and to neoglycolipids containing oligosaccharides derived from these proteins are most compatible with the interpretation that MBP-C interacts primarily with the trimannosyl core of complex N-linked oligosaccharides, with additional ligands being terminal fucose and perhaps also peripheral mannose residues of high mannose type oligosaccharides. This binding specificity is thus quite distinct from that of MBP-A. The presence of multiple MBPs with distinct binding specificities in preparations derived from serum and liver explains conflicting conclusions which have been reached about carbohydrate recognition by these proteins. PMID- 2249984 TI - Expression of biologically active recombinant rat IgE-binding protein in Escherichia coli. AB - IgE-binding protein (epsilon BP) is a protein which has affinity for IgE and was originally identified in rat basophilic leukemia (RBL) cells. Subsequently, it was found to be the rat homolog of CBP35, a murine beta-galactoside-specific lectin. This protein is also designated as L-34 and RL-29 and studied independently by several laboratories. More recently, CBP35 (epsilon BP) was found to be equivalent to Mac-2, a surface marker on activated macrophages. Using rat epsilon BP cDNA, we have succeeded in expressing recombinant epsilon BP in Escherichia coli. Milligram quantities of homogeneous epsilon BP could be obtained from bacterial lysate in a one-step affinity purification procedure utilizing lactosyl-Sepharose 4B and elution with a lactose gradient. The recombinant epsilon BP (r epsilon BP) binds mouse IgE and retains reactivity to anti-peptide antibodies specific for a sequence within rat epsilon BP. The purified r epsilon BP exhibits binding activity to various saccharides, with affinity for N-acetyllactosamine greater than thiodigalactoside greater than lactose much greater than D-galactose greater than L-arabinose, an order identical to that exhibited by native epsilon BP isolated from RBL cells. The recombinant lectin displayed hemagglutination activity when tested with rabbit erythrocytes. Although epsilon BP shares sequence homology to other lectins containing S-type (thiol-dependent) carbohydrate-recognition domains, r epsilon BP is resistant to air oxidation and does not require reducing agents for maintaining its activity. Furthermore, the single cysteine residue appears to be unexposed and can be alkylated only when the protein is denatured in 5.6 M guanidinium hydrochloride. The availability of a source for a large quantity of epsilon BP should facilitate the analysis of biological function(s) and structure activity relationships of this lectin. PMID- 2249988 TI - Blood group A glycolipid antigen expression in kidney, ureter, kidney artery, and kidney vein from a blood group A1Le(a-b+) human individual. Evidence for a novel blood group A heptaglycosylceramide based on a type 3 carbohydrate chain. AB - Kidney, ureter, kidney artery, and kidney vein tissue were obtained from a single human transplant specimen. The donors erythrocyte blood group phenotype was A1Le(a-b+). Total non-acid glycolipid fractions were isolated and individual glycolipid components were identified by immunostaining thin layer plates with a panel of monoclonal antibodies and by mass spectrometry of the permethylated and permethylated-reduced total glycolipid fractions. The dominating glycolipids in all tissues were mono- to tetraglycosylceramides. In the kidney, ureter, and artery tissue less than 1% of the glycolipids were of blood group type, having more than 4 sugar residues. In contrast, 14% of the vein glycolipids were of blood group type, and the dominating components were type 1 chain blood group H pentaglycosylceramides and A hexaglycosylceramides. Trace amounts of structurally different blood group A glycolipids (type 1 to 4 core saccharide chains) with up to 10 sugar residues were found in the kidney, ureter, and vein tissues, including evidence for a novel blood group A heptaglycosylceramide based on the type 3 chain in the vein. The only detected A glycolipid antigen in the artery tissue was the blood group A difucosyl type 1 chain heptaglycosylceramide (ALeb) structure. Blood group Lewis and related antigens (Lea, Leb, and ALeb) were expressed in the kidney, ureter, and artery, but were completely lacking in the vein, indicating that the Le gene-coded alpha 1-4-fucosyltransferase was not expressed in this tissue. The X and Y antigens (type 2 chain isomers of the Lea and Leb antigens) were detected only in the kidney tissue. PMID- 2249986 TI - Purification and characterization of the yeast rDNA binding protein REB1. AB - In the yeast Saccharomyces cerevisiae, the ribosomal RNA genes are present in a single tandem array. A transcriptional enhancer element lies within the spacer region between each rRNA gene, 2.2 kilobases upstream from the transcription initiation site. We have identified previously two proteins, REB1 and REB2, that bind to specific sites within the enhancer (Morrow, B. E., Johnson, S. P., and Warner, J. R. (1989) J. Biol. Chem. 264, 9061-9068). REB1 binds also to a second, higher affinity site near the promoter, 210 base pairs upstream from the initiation site. This report describes the purification and further characterization of REB1. REB1 is a single polypeptide with an apparent molecular mass of 125,000 Da that binds to the sequence CCGGGTAA. It has been found to bind also within transcriptional control regions of several genes transcribed by RNA polymerase II, such as the UASG of the GAL1-GAL10 spacer. Immunoprecipitation analysis demonstrated that REB1 is phosphorylated. PMID- 2249987 TI - Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol linked membrane protein. AB - Uromodulin, originally identified as an immunosuppressive glycoprotein in the urine of pregnant women, has been previously shown to be identical to human Tamm Horsfall glycoprotein (THP). THP is synthesized by the kidney and localizes to the renal thick ascending limb and early distal tubule. It is released into the urine in large quantities and thus represents a potential candidate for a protein secreted in a polarized fashion from the apical plasma membrane of epithelial cells in vivo. After introduction of the full-length cDNA encoding uromodulin/THP into HeLa, Caco-2, and Madin-Darby canine kidney cells by transfection, however, the expressed glycoprotein was almost exclusively cell-associated, as determined by immunoprecipitation after radioactive labeling of the cells. By immunofluorescence, THP was localized to the plasma membranes of transfected cells. In transfected cell extracts, THP also remained primarily in the detergent phase in a Triton X-114 partitioning assay, indicating that it has a hydrophobic character, in contrast to its behavior after isolation from human urine. Triton X 114 detergent-associated THP was redistributed to the aqueous phase after treatment of cell extracts with phosphatidylinositol-specific phospholipase C. Treatment of intact transfected HeLa cells with phosphatidylinositol-specific phospholipase C also resulted in the release of THP into the medium, suggesting that it is a glycosylphosphatidylinositol (GPI)-linked membrane protein. Similar to other known GPI-linked proteins, uromodulin/THP contains a stretch of 16 hydrophobic amino acids at its extreme carboxyl terminus which could function as a GPI addition signal and was shown to label with [3H]ethanolamine. The results indicate that THP is a member of this class of lipid-linked membrane proteins and is released into the urine after the loss of its hydrophobic anchor, probably by the action of a phospholipase or protease. PMID- 2249989 TI - Phorbol ester inhibits surfactant protein SP-A and SP-B expression. AB - Effects of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on expression of pulmonary surfactant proteins, SP-A and SP-B, were determined in a human pulmonary adenocarcinoma cell line (H441-4). TPA decreased cellular SP-A content in association with decreased de novo synthesis of SP-A as assessed by [35S]methionine incorporation. Effects of TPA were time (0-72 h) and dose (IC50 0.5-1.0 nM)-dependent. Phorbol 12,13-dibutyrate (PDBu), and adenosine 5'-O-(3 thiotriphosphate), and 1-oleoyl-2-acetyl-sn-glycerol also decreased SP-A content in these cells. Characteristics of inhibition of SP-A content by PDBu were similar to those of [3H]PDBu binding to H441-4 cells. Inhibitory effects of TPA on SP-A synthesis were associated with concomitant decreases in SP-A mRNA. Expression of a distinct surfactant protein, SP-B, was also markedly decreased after exposure to TPA. SP-A and SP-B mRNA contents decreased more rapidly after treatment with TPA than after actinomycin D. Actinomycin D completely blocked the rapid decrease in SP-A and SP-B mRNAs caused by the phorbol ester, consistent with the concept that the inhibitory effect of TPA on the surfactant protein mRNAs required continued gene transcription and was not mediated solely by changes in SP-A or SP-B transcription. Inhibitory effects of phorbol esters on SP A and SP-B synthesis support the concept that protein kinase C modulates surfactant protein expression in this cell. PMID- 2249991 TI - Free ADP levels in transgenic mouse liver expressing creatine kinase. Effects of enzyme activity, phosphagen type, and substrate concentration. AB - ADP is an important regulator of hepatic metabolism. Despite its importance the level of free ADP in the liver remains controversial. Recently, we engineered transgenic mice which express high levels of creatine kinase in liver. The reaction catalyzed by creatine kinase was assumed to be at equilibrium and used to calculate a free ADP level of 0.059 mumol/g wet weight. In this report we test the equilibrium assumption by studying the free ADP level as a function of enzyme activity or substrate content. Over a 5-fold range of creatine kinase activity, from 150-800 mumol/min/g wet weight, there was no change in the free ADP level. The average value of ADP for these mice was 0.061 +/- 0.016 mumol/g wet weight. Similarly, altering hepatic creatine content from 1.6 to 30 mumol/g wet weight had no effect on the calculated total free ADP level. The average value of ADP for the creatine levels was 0.048 +/- 0.015 mumol/g wet weight. Finally, the free ADP level was calculated using the equilibrium with cyclocreatine rather than creatine as substrate. The equilibrium of the reaction with cyclocreatine lies 30 times more toward phosphorylation than does the equilibrium with creatine. A free ADP level of 0.063 +/- 0.031 mumol/g wet weight was calculated using cyclocreatine. This value is not different from that found with creatine. These results show that the equilibrium assumption used to calculate free ADP levels in transgenic mouse liver is valid, and the presence of creatine kinase does not affect ADP levels. PMID- 2249990 TI - 31P NMR and saturation transfer studies of the effect of Pb2+ on cultured osteoblastic bone cells. AB - The mechanism of lead toxicity at the cellular level remains unknown, although an effect of lead on intracellular Ca2+ has been described. Since bone is a major target for lead, we have investigated the effect of lead on bioenergetic rates and on the intracellular free Mg2+ concentration in cultured osteoblastic bone cells. Using 31P NMR and the saturation transfer technique we have detected a sizable (18%) transfer of saturation from gamma ATP to Pi in a perfused osteoblastic osteosarcoma bone cell line, Ros 17/2.8, and have found a large (greater than 82%) reduction in the Pi----ATP rate upon treatment with 10 microM Pb2+. The NMR-measured unidirectional rate was much greater than the net rate of ATP synthesis through glycolysis and oxidative phosphorylation. By using iodoacetate we investigated the mechanism of the saturation transfer and found that it is catalyzed by the glycolytic enzyme couple glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase. The net rate of glycolysis as measured by lactate production and that of oxidative phosphorylation as measured by O2 consumption were found to be significantly decreased by 18 and 74%, respectively, with lead treatment. In addition, from the chemical shifts of intracellular ATP resonances, we found a significant reduction of 21% in the intracellular free Mg2+ concentration upon Pb2+ treatment. The observed lead-induced reduction in ATP synthesis/utilization and the decrease in intracellular free Mg2+ may contribute to the impairment of bone formation during lead intoxication. PMID- 2249992 TI - Organization of the beta-galactoside alpha 2,6-sialyltransferase gene. Evidence for the transcriptional regulation of terminal glycosylation. AB - Little is currently known about the mechanisms by which the cellular glycosylation machinery is regulated to produce cell type-specific glycosylation sequences on glycoprotein and glycolipid sugar chains. Previously, we have shown that one enzyme involved in terminal glycosylation, beta-galactoside alpha 2,6 sialyltransferase, is expressed in a tissue-specific fashion, with the highest enzyme activity as well as mRNA levels being found in the liver. In addition, the liver mRNA was found to be 4.3 kilobases (kb) in size as compared to a larger message of 4.7 kb in other tissues. To understand the cellular regulation of expression of this sialyltransferase, we have cloned the rat gene encoding the 4.3-kb liver mRNA and found that it spans 40 kb of genomic DNA and contains 6 exons. The gene was found to be very similar in size and exon organization to the murine beta 1,4-galactosyltransferase gene, even though this enzyme has no sequence homology to alpha 2,6-sialyltransferase. The promoter responsible for the production of the liver alpha 2,6-sialyltransferase mRNA is approximately 50 fold more active in a hepatoma cell line known to express this enzyme (HepG2) than in a cell line shown not to express this enzyme (Chinese hamster ovary) and contains consensus binding sites for the liver restricted transcription factors HNF-1 and DBP as well as the transcription factors AP-1 and AP-2. These observations are in accord with the restricted expression of the 4.3-kb mRNA, and provides evidence for the cellular regulation of glycosylation at the level of transcription. PMID- 2249993 TI - Response of rat liver glutaminase to pH, ammonium, and citrate. Possible regulatory role of glutaminase in ureagenesis. AB - Liver glutaminase is stimulated by an increase in NH4+ concentration and NH4+ is an absolute requirement for activity at approximate physiological concentrations of phosphate and glutamine. Increases in the concentration of NH4+ cannot, however, overcome the inhibitory effect of a decrease in pH. In addition, the concentration of NH4+ required for half-maximal rate decreases as pH increases. This decrease is the result of two factors: a direct effect of pH on the apparent affinity of the enzyme for NH4+, and an indirect effect of pH brought about by an increase in the apparent affinity of the enzyme for phosphate which results in a further decrease in the M0.5 for NH4+. In addition, liver glutaminase responds strongly to the concentration of citrate over a physiologically relevant range at approximate physiological concentrations of NH4+, phosphate, and glutamine. An increase in citrate concentration stimulates glutaminase by increasing the affinity of the enzyme for glutamine. The apparent affinity of the enzyme for citrate increases as pH increases. The strong response of liver glutaminase to pH, NH4+, and citrate and the fact that the hydrolysis of glutamine can supply metabolites and effectors for urea synthesis suggest a possible regulatory role of glutaminase in ureagenesis. PMID- 2249994 TI - A 13C NMR study of [5,8-13C2]spermidine binding to tRNA and to Escherichia coli macromolecules. AB - [5,8-13C2]Spermidine was prepared by synthesis, and its binding to macromolecular structures of Escherichia coli was studied. When added to E. coli cells, the two signals of [13C]spermidine (C-5, 47.8 ppm, and C-8, 39.6 ppm; JC-C = 5.8 Hz) were strongly broadened due to binding to macromolecules. When [13C]spermidine was added to E. coli tRNA, the C-5 resonance broadened to v1/2 = 4.7 Hz, whereas the C-8 resonance broadened to v1/2 = 2.7 Hz. tRNA-bound [13C]spermidine could be chased by [12C]spermidine or spermine, but not by putrescine or cadaverine. By using mixtures of [5-13C]- and [8-13C]spermidines (where 13C-13C coupling was avoided), it was possible to estimate a dissociation constant (Kd) of 3 x 10(-3) M using the C-5 v1/2obs values and a Kd of 2.10(-3) M using the C-8 v1/2obs values. The number of spermidine-binding sites (n) could also be estimated by fitting the bound spermidine molar fraction versus tRNA concentration. Values of n = 12 +/- 2 and 14 +/- 3 were obtained for C-5 and C-8, respectively. Measurements of line narrowing at increasing Mg2+ concentrations indicated that approximately 11 spermidines (of the 12-14 bound ones) could be displaced by the former, whereas 3 spermidines remain strongly bound to the tRNA backbone. Measurements of free and bound T1 allowed the determination of a correlation time of 10(-10)s for tRNA-bound spermidine. PMID- 2249995 TI - Site-directed mutagenesis of the m2 muscarinic acetylcholine receptor. Analysis of the role of N-glycosylation in receptor expression and function. AB - The cardiac m2 muscarinic acetylcholine receptor (mAChR) is a sialoglycosylated transmembrane protein which has three potential sites for N-glycosylation (namely, Asn2, Asn3, and Asn6). To investigate the role of N-linked oligosaccharide(s) in the expression and function of the receptor, we constructed glycosylation-defective mutant receptor genes in which the three asparagine codons were substituted by codons for either aspartate (Asp2,3,6), lysine (Lys2,3,6), or glutamine (Gln2,3,6). The glycosylation-defective and wild-type receptor genes were stably expressed in Chinese hamster ovary cells. Binding experiments with the membrane-permeable radioligand [3H]quinuclidinyl-benzilate and the membrane-impermeable radioligand [3H]N-methylscopolamine revealed that the Asp2,3,6, Gln2,3,6, and wild-type receptors were located exclusively on the cell surface and expressed in similar numbers. The Lys2,3,6 mutant receptor was expressed at a relatively low level and was therefore not included in subsequent experiments. Wheat germ agglutinin-Sepharose chromatography and sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis demonstrated that the wild-type receptor, but not the Asp2,3,6 and Gln2,3,6 mutant receptors were N-glycosylated. The Asp2,3,6 and Gln2,3,6 mutant receptors had the same affinities for mAChR ligands as wild-type receptors. The time courses for degradation of the Asp2,3,6, Gln2,3,6, and wild-type receptors were also similar. In vivo functional analysis of the ability of the glycosylation mutant receptors to inhibit forskolin stimulated cAMP accumulation revealed that maximal inhibition of adenylate cyclase activity was similar in the mutant and wild-type receptors. The Asp2,3,6 mutant receptor had an unaltered IC50 value for carbachol while the IC50 value of the Gln2,3,6 mutant receptor was 2-fold higher than that of the wild-type receptor. These results indicate that N-glycosylation of the m2 mAChR is not required for cell surface localization or ligand binding and does not confer increased stability against receptor degradation. Furthermore, N-glycosylation of the m2 mAChR is not required for functional coupling of the m2 mAChR to inhibition of adenylate cyclase. PMID- 2249998 TI - A conserved cysteine in molybdenum oxotransferases. AB - The amino acid sequences of peptides derived from rat hepatic sulfite oxidase have been determined by a combination of amino acid analysis and Edman degradation of the purified protein. The data obtained showed the rat liver enzyme contained 3 cysteine residues which was confirmed by thiol modification studies using 4,4'-dithiodipyridine of the native enzyme. Combining these data with that previously published for chicken liver sulfite oxidase (Neame, P. J., and Barber, M. J. (1989) J. Biol. Chem. 264, 20894-20901) indicates that 2 cysteines (Cys186 and Cys430, based upon the numbering for the chicken sequence) are conserved in both chicken and rat liver enzymes with all the cysteine residues being present in the molybdenum-containing domain. Further comparison of the sequences of the molybdenum domains of rat and chicken liver sulfite oxidase with the amino acid sequences published for the molybdenum domains of a variety of assimilatory nitrate reductases suggests that only a single cysteine residue (Cys186) is conserved in all these enzymes, indicating that it may play a role in the binding of Mo-pterin to the protein. PMID- 2249996 TI - Isolation of polyamine transport-deficient mutants of Escherichia coli and cloning of the genes for polyamine transport proteins. AB - Escherichia coli KK313, which was deficient in spermidine transport, was isolated by treatment of E. coli MA261 with N-methyl-N'-nitro-N-nitrosoguanidine. E. coli NH1596, which was deficient in spermidine transport and has a 90% decreased putrescine transport activity, was obtained by a second treatment of E. coli KK313 with the same mutagen. Genes for polyamine transport systems were isolated by transforming E. coli NH1596 through DNA fragments from E. coli DR112 using pACYC184 as a vector. One clone for the gene of protein(s) catalyzing both putrescine and spermidine uptake (pPT104) was isolated. Two clones for the genes of protein(s) catalyzing only putrescine uptake (pPT79 and pPT71) were obtained. The genes encoded by pPT104, pPT79, and pPT71 were mapped at 15, 19, and 16 min of E. coli chromosome, respectively. Spermidine uptake by NH1596 carrying pPT104, and by MA261, was not inhibited by putrescine and several polyamine analogues, and the Kt values of these two systems were both approximately 0.1 microM. Putrescine transport by NH1596 carrying pPT104 was inhibited completely by spermidine, N,N-dimethyl-4,4'-bipyridylium (paraquat), and N1-acetyl-spermidine, and the Kt value was 1.4 microM. Putrescine uptake by NH1596 carrying pPT79 or pPT71 was not inhibited by spermidine and several polyamine analogues, and the Kt values were 0.5 and 1.8 microM, respectively. In MA261, the putrescine uptake was inhibited by 25-35% by paraquat and N1-acetyl-polyamines and showed two Kt values, 0.5 and 1.5 microM. Based on these findings, the polyamine transport systems of E. coli are discussed. PMID- 2249997 TI - Comparative platelet binding and kinetic studies with normal and variant factor IXa molecules. AB - We have recently shown that thrombin-stimulated human platelets have specific, saturable receptors for factor IXa, occupancy of which promotes factor X activation (Ahmad, S. S., Rawala-Sheikh, R., and Walsh, P. N. (1989) J. Biol. Chem. 264: 3244-3251, 20012-20016; Rawala-Sheikh, R., Ahmad, S. S., and Walsh, P. N. (1990) Biochemistry 29, 2606-2611). To study the structural requirements for factor IXa binding to platelets, equilibrium binding studies and kinetic studies of factor X activation were carried out with normal factor IXa and with two variant proteins: factor IXaAlabama (FIXaAL; Asp47----Gly substitution) and factor IXaChapel Hill (FIXaCH; Arg145----His substitution). In the absence of factors VIIIa and X, there were 331 binding sites/platelet for FIXaCH (Kdapp = 2.8 nM), and 540 sites/platelet for FIXaAL (Kdapp = 3.2 nM), compared with 540 sites/platelet (Kdapp = 2.3 nM) for normal factor IXa. The addition of factors VIIIa and X, both at saturating concentrations, had no effect on the number of binding sites for either normal or variant factor IXa, resulted in a decrease in the Kd for normal factor IXa to 0.67 nM, resulted in a suboptimal decrease in Kd for FIXaAL (1.4 nM), and had no effect on the Kd for FIXaCH. Kinetic studies of factor X activation at variable factor IXa concentration confirmed these values of Kd in the presence of factors VIIIa and X. Determination of rates of factor X activation at variable substrate concentrations yielded normal values of catalytic efficiency (kcat/Km) for the variant proteins, thereby indicating that the abnormally low rates of factor X activation obtained were a consequence of the low affinity binding of FIXaAL and FIXaCH to thrombin-activated platelets in the presence of factors VIIIa and X. These studies suggest that the presence of Asp47 and the cleavage of factor IX at Arg145-Ala146 are important structural features required for specific, high affinity factor IXa binding to platelets in the presence of factors VIIIa and X. PMID- 2249999 TI - Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus. AB - Steroid 21-hydroxylase (P450c21) is absent or defective in more than 90% of patients with congenital adrenal hyperplasia. This disorder of cortisol biosynthesis occurs in a wide spectrum of clinical severity; specific mutations in the 21-hydroxylase gene (CYP21) have been found in association with particular clinical phenotypes. To determine the functional effects of mutations causing amino acid substitutions, normal P450c21 and three mutagenized P450c21 enzymes were expressed at high levels in cultured COS-1 cells using recombinant vaccinia virus. A single amino acid substitution (Val281----Leu) present in patients with mild "nonclassical" 21-hydroxylase deficiency resulted in an enzyme with 20-50% of normal activity. A mutation (Ile172----Asn) identified in patients with the "simple virilizing" form (poor cortisol synthesis but adequate aldosterone synthesis) resulted in an enzyme with less than 2% of normal activity. Finally, a cluster mutation (Ile-Val-Glu-Met234-238----Asn-Glu-Glu-Lys) found in a patient with severe "salt wasting" 21-hydroxylase deficiency (inadequate aldosterone synthesis) results in an enzyme with no detectable activity. These data indicate that the severity of 21-hydroxylase deficiency correlates with the degree of enzymatic compromise. PMID- 2250000 TI - Specificity-determining regions of a lepidopteran-specific insecticidal protein produced by Bacillus thuringiensis. AB - The lepidopteran-specific, insecticidal crystal proteins of Bacillus thuringiensis vary in toxicity to different species of lepidopteran larvae. We report studies of CryIA(a) and CryIA(c), two related proteins that have different degrees of toxicity to Heliothis virescens yet very similar degrees of toxicity to Manduca sexta. The amino acid differences between these proteins are located primarily between residues 280 and 722. We have constructed a series of chimeric proteins and determined their toxicities to both insects. The most significant findings arise from the replacement of three segments of the cryIA(c) gene with homologous portions of the cryIA(a) gene: codons 332-428, 429-447, and 448-722. Each of these segments contributed substantially and largely additively toward efficacy for H. virescens. However, replacement of the 429-447 segment of cryIA(c) gene with the cryIA(a) sequence resulted in a 27-50-fold reduction in toxicity toward M. sexta whereas the reduction in toxicity to H. virescens was only 3-4-fold. Subdivision of the 429-447 segment and replacements involving residues within this segment reduced toxicity to M. sexta by 5- to more than 2000 fold whereas toxicity to H. virescens was only reduced 3-10-fold. These observations indicate that: 1) different but overlapping regions of the cryIA(c) gene determine specificity to each of the two test insects; 2) some of the examined gene segments interact in determining specificity; and 3) different sequences in the cryIA(a) and cryIA(c) genes are required for maximal toxicity to M. sexta. PMID- 2250002 TI - Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis. AB - The thyrotropin (TSH) receptor belongs to a family of guanine nucleotide protein coupled receptors with seven transmembrane-spanning regions joined regulatory together by extracellular and intracellular loops. The cytoplasmic domain comprises three cytoplasmic loops and a cytoplasmic tail that are likely to be important in coupling of the receptor to the guanine nucleotide proteins. To address the question of which portions of the cytoplasmic domain of the TSH receptor are important in this process, we have altered groups of amino acids in the region of the TSH receptor by site-directed mutagenesis. Because of the low affinity of TSH binding to the TSH receptor mutated in the amino terminus of the second cytoplasmic loop and the amino terminus of the cytoplasmic tail, definitive conclusions cannot be made regarding the roles of these regions in signal transduction. However, our data indicate that the first cytoplasmic loop (residues 441-450), the carboxyl-terminal region of the second cytoplasmic loop (residues 528-537), and the carboxyl-terminal (but not the amino-terminal) region of the third cytoplasmic loop (residues 617-625) are important in the ability of the TSH receptor to mediate an increase in intracellular cAMP production. Furthermore, two-thirds of the carboxyl-terminal end of the cytoplasmic tail (residues 709-764; corresponding to the region not conserved between the TSH and lutropin/chorionic gonadotropin receptors) can be removed without functional impairment of the TSH receptor. PMID- 2250001 TI - The role of the bacteriophage T4 gene 32 protein in homologous pairing. AB - The gene 32 protein of the bacteriophage T4 is required for efficient genetic recombination in infected Eschericia coli cells and strongly stimulates in vitro pairing catalyzed by the phage uvsX protein, a RecA-like strand transferase. This helix-destabilizing factor is known to bind tightly and cooperatively to single stranded DNA and to interact specifically with the uvsX protein as well as other phage gene products. However, its detailed role in homologous pairing is not well understood. I show here that when the efficiency of uvsX protein-mediated pairing is examined at different gene 32 protein and duplex DNA concentrations, a correlation between the two is found, suggesting that the two interact in a functionally important manner during the reaction. These and other data are consistent with a model in which the gene 32 protein binds to the strand displaced from the recipient duplex during pairing, thereby stabilizing the heteroduplex product. An alternative model in which the gene 32 protein replaces UvsX on the invading strand, thereby freeing the strand transferase to bind to the displaced strand, is also considered. PMID- 2250003 TI - Structure of a gene for a lysosomal membrane glycoprotein (LEP100). Housekeeping gene with unexpected exon organization. AB - Members of a recently described family of glycoproteins constitute the major protein components of the lysosomal membrane. Changes in glycosylation patterns, redistribution to the cell surface, and increased levels of expression of these proteins are associated, in at least some cases, with cell differentiation, transformation, and metastasis. To understand further the regulation of expression of these proteins and their relationships to each other, we have isolated and characterized the gene for one of these proteins, LEP100, from chicken. Two overlapping clones were isolated which contain the nine exons and eight introns of the 17-kilobase gene for LEP 100. The 5'-flanking region of the gene contains CAAT and TATAAA sequences, but these do not appear to be used as promoter elements. Further downstream are three CCAAT boxes, with no corresponding TATA boxes, which represent putative promoter elements. Multiple CCAAT boxes, the apparent lack of a TATA box, and the GC-rich composition of the 5' region support the classification of the LEP100 gene as a TATA box-lacking housekeeping gene. As further evidence of the housekeeping nature of the LEP100 gene, Northern blots of RNA from several adult and embryonic tissues (skeletal muscle, kidney, liver, heart, gizzard, and brain) revealed a single message for LEP100 of the same size (about 3 kilobases) in each tissue. The gene's introns range in size from 104 to 7200 base pairs. Exons do not represent the four disulfide-bonded loops of the protein, but instead each cysteine of each disulfide-linked pair is encoded by a separate exon. The existence of the same sized mRNA in all tissues indicates that no alternate splicing occurs. The exon organization of the LEP100 gene suggests that it may have evolved from a primordial cysteine-containing exon by gene duplication events. It is likely that the genes of the other members of this family diverged from the same ancestral gene and have a gene organization similar to that of LEP100. PMID- 2250004 TI - Evidence of protein-tyrosine kinase activity in the bacterium Acinetobacter calcoaceticus. AB - Protein phosphorylation was investigated in the bacterium Acinetobacter calcoaceticus both in vivo and in vitro. In cells grown with [32P]orthophosphate, several radioactive phosphoproteins were detected by gel electrophoresis and autoradiography. These proteins were shown to contain phosphoserine, phosphothreonine, and a relatively large proportion of phosphotyrosine residues. Incubation of cellular extracts with [gamma-32P] ATP also resulted in the phosphorylation of several proteins. At least four of them, namely an 81-kDa protein, were modified at tyrosine. No protein labeling occurred when extracts were incubated with [gamma-32P] ATP or [14C]ATP. Moreover, phosphoproteins were insensitive to snake venom phosphodiesterase. All together these results indicate that A. calcoaceticus harbors different protein kinases including a protein tyrosine kinase activity. Further analysis of this activity showed that it has little, if any, functional similarity with eukaryotic protein-tyrosine kinases. PMID- 2250005 TI - Purification and characterization of elongation factor G from bovine liver mitochondria. AB - The mitochondrial protein synthesis translocase elongation factor Gmt (EF-Gmt) from bovine liver has been purified to greater than 90% homogeneity by a combination of conventional gravity and high performance liquid chromatography. The purification scheme results in an approximate overall 14,000-fold purification with 2% total recovery of EF-Gmt activity. Gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicate that the mitochondrial factor is a single polypeptide with a molecular weight of 80,000. EF-Gmt displays similar levels of activity on its homologous mitochondrial ribosomes and on Escherichia coli ribosomes. The mitochondrial translocase is sensitive to temperatures above 37 degrees C, but the factor is partially protected from heat inactivation in the presence of GTP or GDP. The activity of EF-Gmt is inhibited by treatment of the factor with N-ethylmaleimide. In contrast to all other translocases tested to date, EF-Gmt is completely resistant to the inhibiting effect of fusidic acid when tested on its homologous ribosomes. It displays weak sensitivity to this antibiotic when assayed in the presence of heterologous E. coli ribosomes. PMID- 2250006 TI - Regulation of the maltose transport system of Escherichia coli by the glucose specific enzyme III of the phosphoenolpyruvate-sugar phosphotransferase system. Characterization of inducer exclusion-resistant mutants and reconstitution of inducer exclusion in proteoliposomes. AB - Maltose transport in Escherichia coli is regulated at the protein level by the glucose-specific enzyme III (IIIglc) of the phosphoenolpyruvate-sugar phosphotransferase system, by a mechanism known as inducer exclusion. We have isolated and characterized four mutants in the maltose transport system, all of which are in malK, which are resistant to inducer exclusion. The mutations in three of these mutants fall within the COOH-terminal domain of MalK and suggest the first reported function for this domain. Two of these are in a region which shows sequence similarity to lacY and melB, both of which are also regulated by IIIglc, and thus may define a IIIglc-binding domain. We have also reconstituted inducer exclusion in proteoliposomes made from membranes overexpressing the maltose permease. Maltose transport is inhibited by 50-60% when IIIglc is included in the intravesicular space. The inhibition is due to a decrease in the Vmax of transport by a factor of 2. IIIglc does not affect the coupling of ATP hydrolysis to maltose transport, since the ratio of ATP hydrolyzed/maltose transported remained constant in the presence and absence of IIIglc. Finally, the Ki for IIIglc was 40 microM, roughly the same as the in vivo concentration of IIIglc. PMID- 2250007 TI - The multidomain structure of ceruloplasmin from calorimetric and limited proteolysis studies. AB - Differential scanning calorimetry has been used to investigate the thermal stability of three different ceruloplasmins (from sheep, chicken, and turtle) in their native state and after limited proteolysis. The three undegraded proteins showed a similar structural organization in three calorimetric domains, although their temperature of unfolding varied from 57.8 degrees C (turtle) to 71.2 degrees C (sheep) to 82.1 degrees C (chicken). The spectroscopic and the catalytic properties were totally lost at temperatures corresponding to the unfolding of the less thermostable domain in the case of sheep and chicken ceruloplasmins and to the unfolding of the most thermostable domain in the turtle protein. Trypsin, but not plasmin, digestion caused a significant decrease of the thermal stability of sheep and chicken ceruloplasmins. Turtle ceruloplasmin was insensitive to both proteases. Comparing the thermodynamic parameters of the sheep protein in its undegraded and cleaved states revealed a mismatch between the three calorimetric domains and the 3-fold internal replication of the primary structure, which is evident in the highly homologous, fully sequenced human protein. Copper removal caused the rearrangement of the molecule in only two calorimetric domains, suggesting a role of the metal atoms in organizing a new calorimetric domain, which was tentatively assigned to the less thermostable cooperative unit of the native protein. PMID- 2250008 TI - Substrate specificity of prorenin converting enzyme of mouse submandibular gland. Analysis using site-directed mutagenesis. AB - Renin is produced from a larger, inactive precursor, prorenin, through endoproteolytic cleavage at paired basic amino acids. Recently, we have purified and characterized an enzyme, which catalyzes the endoproteolytic process, from mouse submandibular gland. The enzyme, named prorenin converting enzyme, specifically cleaves the peptide bond on the COOH-side of the Arg residue at the Lys-Arg pair of mouse Ren 2 prorenin, but does not cleave mouse Ren 1 and human prorenins. In this study, by synthesizing a series of mutant mouse prorenins using site-directed mutagenesis and the Xenopus oocyte expression system, we have investigated the role of the basic pair as the recognition signal for the enzyme as well as the determinant of the substrate specificity. The results indicate that the basic amino acid at the COOH-side but not at the NH2-side of the basic pair of Ren 2 prorenin is essential for processing directed by prorenin converting enzyme, and that the Arg residue at the COOH-side is more preferable for processing than the Lys. The results also demonstrated that the presence of a Pro residue next to the Lys-Arg pair prevents the processing of Ren 1 prorenin. PMID- 2250012 TI - Characterization of two mutant lactose repressor proteins containing single tryptophans. AB - Two mutant lactose repressors, each containing a single tryptophan, were generated by site-specific mutagenesis. Tyrosine was substituted for tryptophan to be analogous to amber suppression mutants reported previously (Sommer, H., Lu, P., and Miller, J. H. (1976) J. Biol. Chem. 251, 3774-3779). Unlike the amber suppression mutants, plasmids containing the mutant sequences produce large quantities of stable, easily isolable protein. The binding properties of the site specific mutant repressors (W201Y, W220Y) differ from those reported for the corresponding suppression mutants (A201, A220). Whereas minimal effects on operator dissociation rate from lambda plac DNA were noted for the suppression mutants, purified W201Y and W220Y proteins exhibit 10- and 5-fold reduced affinity for a 40-base pair operator, respectively, compared with wild-type. Inducer binding of the A201 and W201Y mutants was similar to that for wild-type repressor, but the inducer affinity of W220Y was approximately 2-fold lower than A220 (approximately 30-fold lower than wild-type). Fluorescence spectra and iodide quenching of the mutant proteins were similar to the suppression mutants, but the absorption coefficient differed significantly from the values reported previously. Acrylamide and iodide quenching results indicate that Trp201 is relatively buried whereas Trp220 is exposed to solvent; inducer binding reduces quenching of Trp220 significantly. CD spectra indicate that the mutant proteins have secondary structural features similar to those of wild-type. Inducer UV difference spectra showed that the major features reported for the wild-type isopropyl beta-D-thiogalactopyranoside difference spectrum were attributable to both tryptophans. In the presence of melibiose, a new minimum appeared in the difference spectra of wild-type and W201Y which was not evident when these proteins bound isopropyl beta-D-thiogalactopyranoside. It is possible that this new feature results from Trp220 involvement in a direct contact with the second sugar in disaccharide inducer molecules such as melibiose and 1,6-allolactose. PMID- 2250010 TI - Interaction of spermatid-specific protein TP2 with nucleic acids, in vitro. A comparative study with TP1. AB - TP2 was purified from rat testes employing a gentle method involving differential salt extraction of the sonication-resistant spermatid nuclei. The nucleic acid binding properties of TP2 were studied by fluorescence quenching, thermal denaturation, circular dichroism techniques and compared with those of TP1 (Singh, J., and Rao, M. R. S. (1987) J. Biol. Chem. 262, 734-740). The tyrosine fluorescence of TP2 was quenched upon binding to double-stranded and denatured DNA and poly(rA). The apparent association constants for binding of TP2 to these nucleic acids were calculated from the fluorescence quenching data, obtained at 50 mM NaCl, and found to be 1.63 x 10(5) M-1, 6.5 x 10(5) M-1, and 7.3 x 10(5) M 1, respectively. Thermal denaturation studies of calf thymus DNA and its complexes with TP2 showed that at 1 mM NaCl, TP2 shifted the Tm from 53 degrees C to 62-67 degrees C, while at 50 mM NaCl, the Tm was shifted from 72 to 78 degrees C suggesting that TP2 is a DNA stabilizing protein. Circular dichroism studies of TP1.DNA and TP2.DNA complexes have revealed that TP2 has a better DNA condensing property than TP1. Furthermore, in contrast to TP1, TP2 does not destabilize in vitro the compactness of liver nucleosome core particles. The DNA binding properties of TP1 and TP2 have been discussed in relation to the significance of their transient appearance during mammalian spermiogenesis. PMID- 2250009 TI - Selective deacylation of arachidonate-containing ethanolamine-linked phosphoglycerides in stimulated human neutrophils. AB - The involvement of the ethanolamine-linked phosphoglyceride fraction (PE) in neutrophil signal transduction is suggested by the stimulus-induced release of arachidonic acid from PE (Chilton, F. H., and Connell, T. R. (1988) J. Biol. Chem. 263, 5260-5265) and by the synthesis of acetylated PE species, predominantly 1-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine (alkenylacetyl-GPE; Tessner, T. G., and Wykle, R. L. (1987) J. Biol. Chem. 262, 12660-12664) in stimulated cells. In the studies reported here, we investigated the relationship between arachidonic acid release from PE and generation of the lysophospholipid precursor required in the biosynthesis of alkenylacetyl-GPE. In order to follow these reactions, we prelabeled neutrophils with 1-O-[3H]alk-1' enyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine (alkenyl-acyl-GPE). We also followed the hydrolysis of endogenous PE by analysis as the dinitrophenyl derivative using a high pressure liquid chromatography method we developed. Our results coupled with those of Chilton et al. (Chilton, F. H., Ellis, J. M., Olson, S. C., and Wykle, R. L. (1984) J. Biol. Chem. 259, 12014-12019) indicate that in human neutrophils the metabolism of alkenylacyl-GPE and alkylacyl-sn glycero-3-phosphocholine (GPC) are strikingly similar with regard to arachidonate metabolism. When added to neutrophils, both 1-O-[3H]alkenyl-2-lyso-GPE and 1-O [3H]alkyl-2-lyso-GPC are acylated predominantly with arachidonic acid, and the resulting arachidonoyl-containing phospholipids are extensively deacylated upon stimulation. However, hydrolysis of PE in the neutrophil differs from hydrolysis of choline-containing phosphoglycerides in that stimulation leads to a greater accumulation of the ethanolamine-linked lysophospholipid. A comparison of the molecular species of endogenous PE (based on molar concentrations measured as the dinitrophenyl derivative) from resting and stimulated neutrophils indicated that only those species which contain arachidonate are significantly hydrolyzed. PMID- 2250011 TI - 12-Hydroxyeicosatetraenoic acid is metabolized by beta-oxidation in mouse peritoneal macrophages. Identification of products and proposed pathway. AB - The products derived from the metabolism of 12-hydroxyeicosatetraenoic acid (12 HETE) by mouse peritoneal macrophages were characterized by high performance liquid chromatography (HPLC) and GC-mass spectrometry. HPLC analysis demonstrated two predominant polar products and several minor ones. The proportion and amounts of these products were dependent on the concentration of 12-HETE, the number of macrophages incubated with the monohydroxy fatty acid, and the time of incubation. The products identified by GC-mass spectrometry suggested that 12 HETE had undergone beta-oxidation. The intermediates identified were: 3,12 dihydroxy-5,8,10,14, 20:4; 10-hydroxy-3,6,8,12, 18:4; 3,10-dihydroxy-6,8,12, 18:3; 8-hydroxy-4,6,10, 16:3; 6-hydroxy-4,8, 14:2; and 4-hydroxy, 12:1. The major products, as identified by HPLC and GC-mass spectrometry, were 8-hydroxy-4,6,10, 16:3 and 4-hydroxy, 12:1. A minor product, 10-hydroxy-6,8,12, 18:3 was postulated to arise from either the isomerization and reduction of 10-hydroxy-3,6,8,12, 18:4 or from chain elongation of 8-hydroxy-4,6,10, 16:3. Inhibiting cyclooxygenase and lipoxygenase activities by ibuprofen and nordihydroguaiaretic acid, respectively, did not inhibit the formation of these products. 82% to 98% of 12-HETE was converted and released into the medium as products of beta-oxidation. The remainder was taken up into cellular lipids. beta-Oxidation of 12-HETE was decreased by only 12 and 21% after inhibiting mitochondrial fatty acid oxidation by 89 and 93% by 5 and 100 microM concentrations of the mitochondrial fatty acid oxidation inhibitor, methyl palmoxirate, respectively. It is thus postulated that the beta-oxidation of 12-HETE by mouse peritoneal macrophages occurs in peroxisomes. PMID- 2250014 TI - Isolation and characterization of disulfide-bonded peptides from the three globular domains of aggregating cartilage proteoglycan. AB - The aggregating cartilage proteoglycan core protein contains two globular domains near the N terminus (G1 and G2) and one near the C terminus (G3). The G1-G3 domains contain 10, 8, and 10 cysteine residues, respectively. The disulfide assignments of the G1 domain have previously been deduced (Neame, P. J., Christner, J. E., and Baker, J. R. (1987) J. Biol. Chem. 262, 17768-17778) as Cys1-Cys2, Cys3-Cys6, Cys4-Cys5, Cys7-Cys10, and Cys8-Cys9, in which the numbers cited after the half-cystine residues are their relative positions from the N terminus. Here we describe a method for the isolation of disulfide-bonded peptides from tryptic digests of bovine nasal cartilage monomer. Sequence analysis of these peptides has allowed us to confirm the pairings previously determined for the G1 domain and to assign a disulfide pattern for the G2 domain of Cys11-Cys14, Cys12-Cys13, Cys15-Cys18, and Cys16-Cys17, in which the Cys15 Cys18 pairing was deduced indirectly. Similarly, for the G3 domain, a pattern of Cys19-Cys20, Cys21-Cys24, Cys22-Cys23, Cys25-Cys27, and Cys26-Cys28 was assigned, in which the Cys22-Cys23 pair was deduced indirectly. The G2 domain therefore contains disulfide bonding which is characteristic of the tandem repeat structures found in the G1 domain and link protein, and the G3 domain contains the three disulfide linkages previously assigned to the family of C-type animal lectins. The method described here, which combines anion-exchange, cation exchange, and reversed-phase chromatography, should have broad application to the isolation of disulfide-bonded peptides from other heavily glycosylated proteins and proteoglycans. PMID- 2250013 TI - Characterization of a tubular basement membrane component reactive with autoantibodies associated with tubulointerstitial nephritis. AB - A kidney tubular basement membrane (TBM) component that is bound by antibodies from individuals with anti-TBM antibody-associated tubulointerstitial nephritis (TIN) was purified and characterized (TIN antigen). TIN antigen was prepared from rabbit TBM by extraction with guanidine and purified by ion-exchange, gel filtration, and reversed-phase chromatography. Based upon yields of protein and antibody reactivity, TIN antigen accounts for about 9% of the mass of TBM and thus is a major component of this basement membrane. A predominant 58-kDa form comprises about 90% of purified TIN antigen, and a 50-kDa form accounts for the remainder. The two forms share the amino-terminal sequence Ser-Ile-Phe-Gln-Gly Gln-Tyr-X-Arg-Ser-Phe-Gly- and give similar tryptic peptide maps, indicating that they are structurally related. Their amino acid compositions overall are similar to laminin and entactin/nidogen. The absence of hydroxyproline and hydroxylysine and the low levels of glycine in TIN antigen indicate that it is noncollagenous. No similarities were found between other known proteins and sequences of tryptic peptides and the amino terminus of TIN antigen, suggesting that it is distinct from other characterized basement membrane components. A goat polyclonal antibody toward rabbit TIN antigen showed the same kidney distribution as human antibodies and was completely inhibited in enzyme-linked immunosorbent assay by purified TIN antigen. These data further support the idea that TIN antigen is the primary target for anti-TBM antibodies associated with TIN. This research presents methods to prepare TIN antigen for biochemical studies and investigations of its role in anti-TBM autoimmune TIN. PMID- 2250015 TI - The biosynthesis of cyanogenic glucosides in higher plants. Identification of three hydroxylation steps in the biosynthesis of dhurrin in Sorghum bicolor (L.) Moench and the involvement of 1-ACI-nitro-2-(p-hydroxyphenyl)ethane as an intermediate. AB - N-Hydroxytyrosine, (E)- and (Z)-p-hydroxyphenyl-acetaldehyde oxime, p hydroxyphenylacetonitrile, and p-hydroxymandelonitrile are established intermediates in the biosynthesis of the tyrosine-derived cyanogenic glucoside dhurrin (Halkier, B. A., Olsen, C. E., and Moller, B. L. (1989) J. Biol. Chem. 264, 19487-19494. Simultaneous measurements of oxygen consumption and biosynthetic activity using a microsomal enzyme system isolated from etiolated sorghum seedlings demonstrate a requirement for three oxygen molecules in the conversion of tyrosine to p-hydroxymandelonitrile. Two oxygen molecules are consumed in the conversion of tyrosine to (E)-p-hydroxyphenylacetaldehyde oxime, indicating the existence of a previously undetected hydroxylation step in addition to that resulting in the formation of N-hydroxytyrosine. Radioactively labeled 1-nitro-2-(p-hydroxyphenyl)ethane was chemically synthesized and tested as a possible intermediate. Biosynthetic experiments demonstrate that the microsomal enzyme system metabolizes the nitro compound to the subsequent intermediates in dhurrin synthesis (Km = 0.05 mM; Vmax = 14 nmol/mg of protein/h). Low amounts of 1-nitro-2-(p-hydroxyphenyl)ethane are produced in the microsomal reaction mixtures when tyrosine is used as substrate. These data support the involvement of 1-nitro-2-(p-hydroxyphenyl)ethane or more likely its aci-nitro tautomer as an intermediate between N-hydroxytyrosine and p hydroxyphenylacetaldehyde oxime. The conversion of (E)-p hydroxyphenylacetaldehydeoxime to p-hydroxymandelonitrile requires a single oxygen molecule. The oxygen molecule is utilized for hydroxylation of p hydroxyphenylacetonitrile into p-hydroxymandelonitrile. This indicates that the conversion of p-hydroxyphenylacetaldehyde oxime into p-hydroxyphenylacetonitrile proceeds by a simple dehydration reaction. PMID- 2250016 TI - Rhizobium leguminosarum exoB mutants are deficient in the synthesis of UDP glucose 4'-epimerase. AB - Rhizobium leguminosarum bv. viciae Exo- mutant strains RBL5523,exo7::Tn5,RBL5523,exo8::Tn5 and RBL5523,exo52::Tn5 are affected in nodulation and in the syntheses of lipopolysaccharide, capsular polysaccharide, and exocellular polysaccharide. These mutants were complemented for nodulation and for the syntheses of these polysaccharides by plasmid pMP2603. The gene in which these mutants are defective is functionally homologous to the exoB gene of Rhizobium meliloti. The repeating unit of the residual amounts of EPS still made by the exoB mutants of R. leguminosarum bv. viciae lacks galactose and the substituents attached to it. The R. leguminosarum bv. viciae and R. meliloti exoB mutants fail to synthesize active UDP-glucose 4'-epimerase. PMID- 2250019 TI - A positively charged region is a determinant of the orientation of cytoplasmic membrane proteins in Escherichia coli. AB - Basic amino acid residues were introduced into an extracellular (periplasmic) domain, preceding a membrane-spanning hydrophobic domain, of SecY, an integral cytoplasmic membrane protein. The localization of the domain was monitored as to the alkaline phosphatase activity of TnPhoA fused adjacent to the domain. The alkaline phosphatase activity of such Escherichia coli cells drastically decreased when positive charges were introduced, indicating that on the introduction the SecY domain showed a change in localization from the periplasm to the cytoplasm. In another experiment, positive charges were introduced to the same periplasmic domain of another SecY-PhoA fusion protein, in which PhoA is fused to the cytoplasmic domain of SecY following the particular hydrophobic domain. The alkaline phosphatase activity increased drastically when positive charges were introduced, indicating that the SecY domain fused to PhoA showed a change in localization from the cytoplasm to the periplasm. In both experiments, the removal of a large amino-terminal portion of the SecY domain did not alter the effect of the positive charge introduction. Changes in localization of SecY domains thus demonstrated were also supported by a protease accessibility test on spheroplasts. It is proposed that a positively charged region adjacent to a membrane-embedded hydrophobic region tends to be stabilized on the cytoplasmic surface of the membrane, which in turn endows the hydrophobic region with the ability to act as a stop-transfer sequence or a signal sequence and consequently determines the orientation of the hydrophobic region in the membrane. PMID- 2250018 TI - RNA splicing in Chlamydomonas chloroplasts. Self-splicing of 23 S preRNA. AB - The 23 S rRNA gene of the Chlamydomonas reinhardtii chloroplast contains an 888 base pair intron with structural features characteristic of Group I introns. The nuclear, chloroplast ribosome-deficient mutant of C. reinhardtii, ac20, overaccumulates a approximately 3.6-kilobase unspliced 23 S preRNA compared to wild-type cells. We have used [alpha-32P]GTP labeling of total RNA preparations from ac20 to rapidly determine that 23 S preRNA is capable of self-splicing. The ability of the 23 S intron (with flanking exon sequences) to correctly catalyze its own splicing was confirmed using RNA produced by in vitro transcription of cloned DNA. These results identify the first example of a self-splicing RNA of chloroplast origin. PMID- 2250017 TI - Cooperative interaction of nuclear factor-kappa B- and cis-regulatory enhancer binding protein-like factor binding elements in activating the interleukin-8 gene by pro-inflammatory cytokines. AB - A novel cytokine, interleukin-8 (IL-8), may play major roles in the inflammatory process by recruiting neutrophils and T cells into inflammatory sites. The production of this cytokine is not constitutive and is induced in a variety of cell types by stimulation with mitogens and cytokines. Among cytokines, only IL-1 and tumor necrosis factor (TNF) can induce IL-8 gene expression at the transcriptional level. Transfection of a human fibrosarcoma cell line with chloramphenicol acetyltransferase expression plasmids linked to a 5'-flanking deletion mutants of the IL-8 gene demonstrated that the nucleotides between -94 and -71 base pairs from the start of the first exon are essential and sufficient for the IL-8 induction by either IL-1, TNF, or phorbol 12-myristate 13-acetate. This sequence is composed of two cis-elements; one is the potential binding site for a nuclear factor-kappa B-like factor and the other for a cis-regulatory enhancer binding protein-like factor. Mutations in either elements abolished IL 1, TNF, and phorbol 12-myristate 13-acetate responsiveness. This report provides the first evidence that cooperation between two distinct cis-elements may be required for induction of gene expression by either IL-1 or TNF. PMID- 2250020 TI - Mitochondrial proton/phosphate transporter. An antibody directed against the COOH terminus and proteolytic cleavage experiments provides new insights about its membrane topology. AB - Molecular cloning and sequencing of a full-length cDNA encoding the rat liver mitochondrial phosphate transporter (H+/Pi symporter) has revealed its primary structure (Ferreira, G. C. Pratt, R. D., and Pedersen, P. L. (1989) J. Biol. Chem. 264, 15628-15633). To date, no experimental data pertinent to the membrane topology of this transporter are available. For this reason, four different peptides which represent different regions of the H+/Pi symporter were synthesized and used to raise polyclonal antibodies. Each of the antipeptide antibodies exhibits immunoreactivity with its synthetic peptide antigen, but only antiserum against a COOH-terminal peptide reacts with the native transporter, suggesting that the other peptides are either conformally restricted or located in the interior of the protein. Competitive radioimmunoassays, using intact "mitoplasts" (outer membrane-free mitochondria) and inverted inner membrane vesicles, show that the COOH-terminal antibodies bind only to the cytoplasmic surface of the inner membrane, indicating that the COOH terminus of the protein is normally exposed to the mitochondrial intermembrane space. In support of this conclusion, tryptic digestion of mitoplasts but not of the inside-out vesicles, cleaves the antigenic site for the COOH-terminal antibodies. In other experiments, it was shown that N-ethylmalemide, a sulfhydryl alkylating agent known to inhibit the mitochondrial phosphate transporter, markedly reduces the accessibility of the COOH terminus to trypsin. These studies provide the first direct experimental data relevant to the membrane topology of the mitochondrial H+/Pi symporter. In addition, they support the view that alkylation of a reactive cysteine residue induces a significant conformational change in the transporter. PMID- 2250021 TI - Fractionation of the general RNA polymerase II transcription factors from Drosophila embryos. AB - We have subdivided the components of the basic RNA polymerase II machinery from Drosophila embryos into three fractions and RNA polymerase II. The RNA polymerase II was 90% homogeneous and possessed the IIa form of the largest subunit. By substitution of these factors with their mammalian homologues in reconstituted transcription reactions, we have determined that the three Drosophila fractions contain transcription factor (TF)IIB, TFIIE/F, and TFIID. In addition, the fraction with TFIID contains another essential activity, which we have tentatively designated as TFIIZ. There was no apparent requirement for TFIIA. The reconstituted transcription factors accurately transcribe both Drosophila and mammalian genes. This fractionated system should serve as a source of general transcription factors for the study of RNA polymerase II transcription in Drosophila as well as other eukaryotes. PMID- 2250022 TI - Cloning, structural analysis, and expression of the human slow twitch skeletal muscle/cardiac troponin C gene. AB - The two isoforms of troponin C that are differentially expressed in slow and fast twitch skeletal muscle are encoded by single copy genes. We are analyzing the mechanisms that control their highly restricted pattern of differential expression. The structure of the human fast twitch troponin C isoform gene has been reported (Gahlmann, R. and Kedes, L. (1990) J. Biol. Chem. 265, 12520 12528). Here we describe the isolation, nucleotide sequence, and localization of a regulating promoter element sufficient to impart expression of the human slow twitch skeletal muscle troponin C gene which is also the isoform expressed in heart. The 3.0-kilobase gene is composed of 6 exons and 5 introns. Introns and 5' flanking sequences between the human and mouse slow troponin C genes are highly conserved. The gene is transcribed from the same start site in skeletal and cardiac muscle. A consensus TATA box is located 29 base pairs upstream of the transcriptional start site but no canonical CAAT box was observed. Cell transfection experiments provided evidence that promoter elements that are responsible for a cell type-specific pattern of gene expression are located in the 5'-flanking sequences. Constructs comprising 4.0 kilobases of 5'-flanking sequences, attached upstream of the chloramphenicol transferase gene as reporter, were expressed at high levels in differentiated cells of three myogenic cell lines (C2, L8, and H9c2(2-1)) and also at high levels in undifferentiated C2 and H9c2(2-1) cells. Chloramphenicol acetyltransferase activity was not detected in either WI38 cells or monkey kidney cells, CV-1. 5'-Deletion constructs were assayed for expression in differentiated H9c2(2-1) and C2 cells. Sequences between base pairs -67 and +24 were sufficient for high level expression in these cell lines. PMID- 2250023 TI - Insulin receptor tyrosine residues 1162 and 1163 control insulin stimulation of myristoyl-diacylglycerol generation and subsequent activation of glucose transport. AB - Chinese hamster ovary (CHO) transfectants expressing human insulin receptors that were mutated at tyrosines 1162 and 1163 (CHO-Y2 cells) exhibit decreased insulin stimulation of both receptor tyrosine kinase and 2-deoxyglucose uptake compared with transfectants expressing wild-type human insulin receptors (CHO-R cells). We now provide evidence that insulin stimulation of myristoyl-diacylglycerol (DAG) production is also markedly impaired in CHO-Y2 cells; this is manifested as a decreased responsiveness and sensitivity to insulin as compared with CHO-R and parental CHO cells. Further, we report that (i) the concentration-response curves of insulin-stimulated myristoyl-DAG production and 2-deoxyglucose uptake were superimposable within each of the three cell lines. (ii) The insulin-induced increase in myristoyl-DAG production preceded that in 2-deoxyglucose uptake, and the time course was altered for both responses in CHO-Y2 cells. (iii) Insulin also increased the phosphorylation of a 40-kDa protein known to be a substrate for protein kinase C, but to a much lesser extent in CHO-Y2 cells than in CHO-R cells. (iv) Exogenously added 1,2-dimyristoyl-glycerol and 4 beta-phorbol 12 beta myristate 13 alpha-acetate (PMA) again stimulated both the phosphorylation of the 40-kDa protein and 2-deoxyglucose uptake, but in contrast to insulin, they elicited the same level of response in both CHO-R and CHO-Y2 cells. (v) Finally, in protein kinase C-depleted CHO-R cells, insulin and PMA stimulation of 40-kDa protein phosphorylation as well as PMA stimulation of 2-deoxyglucose uptake were completely abolished whereas insulin-stimulated 2-deoxyglucose uptake was only partially decreased. Taken together, these results suggest that insulin stimulation of 2-deoxyglucose uptake involves myristoyl-DAG production and, at least in part, protein kinase C activation, all three of these processes being controlled by receptor tyrosines 1162 and 1163. PMID- 2250024 TI - Rat brain N-acetylated alpha-linked acidic dipeptidase activity. Purification and immunologic characterization. AB - N-Acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase) is a membrane bound metallopeptidase that cleaves glutamate from the endogenous neuropeptide N acetyl-L-aspartyl-L-glutamate. In this report, we have solubilized NAALA dipeptidase activity from synaptosomal membranes with Triton X-100 and purified it to apparent homogeneity by sequential column chromatography on DEAE-Sepharose, CM-Sepharose, and lentil lectin-Sepharose. This procedure resulted in a 720-fold purification with 1.6% yield. The purified ezyme migrated as a single silver stained band on a sodium dodecyl sulfate gel with an apparent molecular weight of 94 kDa. Using an enzymatic stain to visualize NAALA dipeptidase activity within a gel matrix, we have confirmed that the 94-kDa band is, indeed, NAALA dipeptidase. The purified enzyme was characterized and found to be pharmacologically similar to NAALA dipeptidase activity described previously in synaptosomal membrane extracts. Using the purified NAALA dipeptidase as antigen, we have raised specific and high titer polyclonal antibodies in guinea pig. Immunocytochemical studies show intense NAALA dipeptidase immunoreactivity in the cerebellar and renal cortices. PMID- 2250025 TI - Increases in phosphatidic acid levels accompany sphingosine-stimulated proliferation of quiescent Swiss 3T3 cells. AB - Sphingosine, a breakdown product of cellular sphingolipids, has recently been shown to stimulate DNA synthesis and act synergistically with known growth factors to induce proliferation of quiescent Swiss 3T3 fibroblasts (Hong, Z., Buckley, N. E., Gibson, K., and Spiegel, S. (1990) J. Biol. Chem. 265, 76-81). The present study demonstrates that mitogenic concentrations of sphingosine induce early increases in cytosolic phosphatidic acid, which is a potent mitogen for Swiss 3T3 cells. Structurally related analogs of sphingosine, such as N stearoylsphingosine and other long chain aliphatic amines, did not mimic the mitogenic effect of sphingosine and did not elevate phosphatidic acid levels. Sphingosine not only stimulated [3H]thymidine incorporation with similar efficiency and kinetics as phosphatidic acid, it also induced similar morphological alterations. Both sphingosine and phosphatidic acid acted synergistically with a variety of growth factors, such as, insulin, epidermal growth factor, fibroblast growth factor, and 12-O-tetradecanoylphorbol 13 acetate. In sharp contrast, sphingosine and phosphatidic acid did not have additive or synergistic effects in either the presence or absence of other growth factors. Both sphingosine and phosphatidic acid stimulated DNA synthesis in cells made protein kinase C-deficient by prolonged treatment with phorbol ester and sphingosine still stimulated similar increases in phosphtidic acid in these cells. Furthermore, similar to the actions of phosphatidic acid on signal transduction in Swiss 3T3 cells, mitogenic concentrations of sphingosine also inhibit cAMP accumulation and trigger the hydrolysis of polyphosphoinositides. Our findings indicate that sphingosine and phosphatidic acid control cellular responses in Swiss 3T3 cells through a common pathway. In view of the prominent role of phosphatidic acid in signal transduction and cellular proliferation, our observations that sphingosine, at mitogenic concentrations, increases the level of phosphatidic acid and also mimics the effects of phosphatidic acid on signal transduction, have important implications for the mechanism of action of sphingosine. PMID- 2250026 TI - Tropomyosin prevents depolymerization of actin filaments from the pointed end. AB - Regulation of the pointed, or slow-growing, end of actin filaments is essential to the regulation of filament length. The purpose of this study is to investigate the role of skeletal muscle tropomyosin (TM) in regulating pointed end assembly and disassembly in vitro. The effects of TM upon assembly and disassembly of actin monomers from the pointed filament end were measured using pyrenyl-actin fluorescence assays in which the barbed ends were capped by villin. Tropomyosin did not affect pointed end elongation; however, filament disassembly from the pointed end stopped in the presence of TM under conditions where control filaments disassembled within minutes. The degree of protection against depolymerization was dependent upon free TM concentration and upon filament length. When filaments were diluted to a subcritical actin concentration in TM, up to 95% of the filamentous actin remained after 24 h and did not depolymerize further. Longer actin filaments (150 monomers average length) were more effectively protected from depolymerization than short filaments (50 monomers average length). Although filaments stopped depolymerizing in the presence of TM, they were not capped as shown by elongation assays. This study demonstrates that a protein, such as TM, which binds to the side of the actin filament can prevent dissociation of monomers from the end without capping the end to elongation. In skeletal muscle, tropomyosin could prevent thin filament disassembly from the pointed end and constitute a mechanism for regulating filament length. PMID- 2250027 TI - Transcription preferentially inhibits nucleotide excision repair of the template DNA strand in vitro. AB - It has been reported that pyrimidine dimers (pyrimidine mean value of pyrimidine) are removed preferentially from actively transcribing genes. Furthermore, the preferential repair is restricted to the transcribed strand of these genes. Currently there is no mechanistic explanation for these phenomena. In this study we investigated the effect of transcription on nucleotide excision repair using defined Escherichia coli systems consisting of DNA substrates containing a strong promoter and either (a) a T mean value of T at a defined position in the nontranscribed or transcribed strand or (b) photoproducts randomly distributed in both strands, as well as transcription and nucleotide excision repair enzymes. While a T mean value of T in the nontranscribed strand had no effect on transcription, a photodimer in the transcribed strand blocked transcription causing RNA polymerase to stall at the T mean value of T site. This stalled elongation complex inhibited the excision of the photodimer by (A)BC excinuclease resulting in a net effect of preferential repair of the nontranscribed strand in a mixture containing both substrates. Similarly, when we conducted transcription/repair experiments with a superhelical plasmid no enhanced repair of the transcribed gene was observed compared to nontranscribed regions. We conclude that RNA polymerase stalled at a photodimer does not direct the (A)BC excinuclease to the damaged template strand and therefore cannot account for the strand-specific repair observed in vivo. PMID- 2250029 TI - Low density lipoprotein receptor-related protein mediates endocytosis of monoclonal antibodies in cultured cells and rabbit liver. AB - Monoclonal antibodies that bound to the external domain of the rabbit low density lipoprotein receptor-related protein (LRP) were taken into rabbit fibroblasts by receptor-mediated endocytosis. Uptake occurred in fibroblasts from Watanabe heritable hyperlipidemic rabbits, which lack low density lipoprotein receptors, as well as in normal rabbit fibroblasts. The fate of the internalized antibodies differed, depending on the domain of LRP that was recognized. LRP is synthesized as a single polypeptide chain that is cleaved to form a heterodimer of two noncovalently bound proteins, 1) a 515-kDa subunit that contains the binding domain, and 2) an 85-kDa subunit that contains the membrane-spanning region and cytoplasmic tail. A monoclonal antibody directed against the 515-kDa subunit (anti-LRP 515) rapidly dissociated from LRP at pH 5.2. After uptake by cells this antibody dissociated from the receptor and was degraded in lysosomes. A second antibody directed against the external portion of the 85-kDa subunit (anti-LRP 85) failed to dissociate at acid pH. After uptake by cells this antibody was not degraded, but instead was released from the cells in an acid-precipitable form. When administered intravenously to rabbits, both 125I-labeled antibodies were rapidly cleared from the circulation, 75-95% of the uptake occurring in the liver. The anti-LRP 515 antibody was degraded and acid-soluble products appeared in the plasma. No significant acid-soluble products appeared when the anti-LRP-85 antibody was infused. We conclude that LRP can carry out receptor-mediated endocytosis and that its ligand-binding domain, like the similar domain of the low density lipoprotein receptor, undergoes an acid-dependent conformational change that ejects ligands within the endosome. We also conclude that in the body this endocytotic function is expressed primarily in the liver. Both of these conclusions lend support to the hypothesis that LRP may function in humans and animals as a receptor for apolipoprotein E-enriched lipoproteins, such as chylomicron remnants. PMID- 2250028 TI - Antimicrobial tachyplesin peptide precursor. cDNA cloning and cellular localization in the horseshoe crab (Tachypleus tridentatus). AB - The hemocytes of the horseshoe crab have been found to contain a new family of Arthropodous antibiotics, termed the "tachyplesin family." These peptides are composed of 17-18 amino acid residues with a carboxyl-terminal arginine alpha amide. We report here the entire cDNA sequence coding for the tachyplesin precursors and their distribution in various tissues of the horseshoe crab. Sequence analysis of the cloned cDNAs revealed that the tachyplesin precursors consist of 77 amino acids with 23 residues in a presegment, and that there are two types of mRNAs corresponding to the isopeptides tachyplesins I and II. Both precursors contain a putative signal peptide, a processing peptide sequence and a carboxyl-terminal amidation signal "Gly-Lys-Arg" connected to the mature tachyplesin peptide. Moreover, an unusual acidic amino acid cluster, Asp-Glu-Asp Glu-Asp-Asp-Asp-Glu-Glu-COOH, is present in the carboxyl-terminal portions of both precursors. These results suggest that the two types of tachyplesin precursors are first synthesized as preproproteins and are then incorporated into the intracellular organelle, accompanied by various processing events. Northern blot analysis on a total RNA from various tissues of the horseshoe crab revealed that the tachyplesin precursors are expressed mainly in hemocytes and cardiac and brain tissues. Tachyplesin was immunohistochemically localized in the smaller dense granules rather than the typical large granules present in abundance in the hemocytes. PMID- 2250030 TI - Serine-rich ultra high sulfur protein gene expression in murine hair and skin during the hair cycle. AB - To study the regulation of hair differentiation, a murine genomic clone, gUHS-SER M16, was isolated that contained two members of the family of serine-rich ultra high sulfur protein genes. One of the genes, gUHS-SER-1, encodes 230 amino acids with 40% cysteine and 23% serine; the other gene, gUHS-SER-2, encodes 223 amino acids with 41% cysteine and 21% serine. The similarity between the two genes is 73%, and both have several 10-amino acid repeats within their coding regions. In the prospective promoter region, there are several regions of similarity including a "TATA" box, with neither gene having a "CAT" box. At the 3' untranslated region, there is no similarity, and thus a fragment from this region was used as a hybridization probe for RNA dot-blots and for in situ hybridizations. The RNA dot-blot showed elevated levels of mRNA during the active phases of hair growth and low levels during the resting phases. In situ hybridizations show that mRNA for the ultra high sulfur protein gene is found during the active phases of the hair cycle not only in the medulla and the inner root sheath of the forming hair but also in upper layers of the epidermis of skin. PMID- 2250031 TI - Ribonuclease A as a substrate of the protease from human immunodeficiency virus 1. AB - Bovine pancreatic ribonuclease A (RNase) contains two bonds, Met29-Met30 and Tyr92-Pro93 which are representative of sites in the human immunodeficiency virus 1 (HIV-1) gag polyprotein precursors that are cleaved by the HIV-1 protease during viral maturation. Nevertheless, neither native nor performic acid-oxidized RNase is a substrate for the protease. However, RNase derivatives obtained by reduction and S-alkylation with iodoacetate or iodoacetamide undergo cleavage by the HIV-1 protease at a single site, Ala109-alkyl-Cys110, that is distinct from either of the two predicted bonds mentioned above. The neutral carboxyamido methylcysteinyl derivative is cleaved 8 times faster than that containing the negatively charged carboxy-methyl substituent at P1'. Succinylation of these S alkylated RNase derivatives creates a second site of cleavage by the protease between succinyl-Lys7 and Phe8. Thus, the pattern of cleavage of denatured RNase by the HIV-1 protease can be manipulated by chemical derivatization of the substrate, and the new sites of hydrolysis revealed by these studies add to our understanding of the specificity of this important enzyme. PMID- 2250032 TI - Age at marriage in Sri Lanka: stabilizing or declining? AB - Over the last four decades in Sri Lanka, age at first marriage for males increased marginally, and for females it rose considerably, but there has been no recent increase in female age at marriage. Among the younger cohorts, estimated ages at which some married indeed show a declining mean age at marriage. Coale McNeil estimates indicate that there is no real decline in female age at marriage in Sri Lanka. Marriages were delayed as a result of economic hardship or increased mortality to the mid-1970s, but once the overall economy improved after 1977, more marriages took place. Female age at marriage in Sri Lanka remained slightly below 24 years, the age which is anticipated by younger cohorts, and this level is likely to persist for some time. PMID- 2250035 TI - The desire for children in tropical Africa: the influence of relatives on fertility decisions in Ankole, Uganda. AB - In a survey in Ankole (Uganda) in 1985, 1664 women in samples of the three socioeconomic groups (pastoralists, cultivators and mixed farmers) were asked questions on their reproductive history, and 1029 men questions on educational and wedding costs and their expectations of help from relatives and obligations to help relatives. It is shown that the extended family system allows a great deal of mutual support, while the power of the elders allows them to influence younger married relatives to follow the pronatalist traditions of the society. PMID- 2250033 TI - Predicting contraceptive method usage among women in west Scotland. AB - Users of the six major methods of contraception are compared across a broad range of variables using data from a community sample. Differences between the groups were apparent for a range of socioeconomic and reproductive variables, and current users of the various methods also differed in their past use of contraception. Users of barrier methods fared particularly well. Few differences were observed for current health status or for the sociocultural variables examined, although users of natural methods differed from all others in their religious affiliation and commitment. Discriminant analysis showed that the most predictive variables distinguishing women who had opted for permanent methods of contraception (female sterilization and vasectomy) were the woman's stated reason for using her current method and her past contraceptive patterns; the inclusion of social, health and reproductive indicators did little to improve the prediction. It is argued that heightened expectations for contraceptive efficacy in the face of increasing concerns about long-term health consequences have contributed to the increased use of permanent methods. PMID- 2250034 TI - Vasectomy reversal in Nepal. AB - Data from 157 men in Nepal who had vasectomy reversal are analysed. Most sought reversal within 5 years of vasectomy. Half of the men sought reversal because of the death of a male child, and about one-fourth because of the loss of a female child. Re-marriage was the primary reason for only 10% of the men. Those having reversal because of the loss of a male child were generally younger, and for almost half of this group, the age of their last child at the time of their vasectomy was under 2 years. The results suggest that the demand for reversal could be considerably reduced by more careful screening of the potential vasectomy acceptors. PMID- 2250036 TI - Demographic and socioeconomic factors affecting infant mortality in Egypt. AB - This paper analyses the relative importance of demographic and socioeconomic factors with respect to their role in reducing infant mortality in Egypt. Logit analyses of data from a nationally representative sample of Egyptian households, and for urban and rural households separately, indicate that demographic factors have more effect on infant mortality than socioeconomic factors. The results also show the need to improve housing in urban areas and sewerage systems in rural areas in order to reduce infant mortality. One of the most important policy conclusions, however, concerns the importance of providing a vigorous educational campaign to enlighten mothers and prospective mothers in both rural and urban areas on the positive effects of breast-feeding, longer birth intervals, and fewer children on the survival of infants. PMID- 2250038 TI - Fertility preferences among Malaysian women: an analysis of responses to the new population policy. AB - About 10% of 3887 ever-married women included in the 1984-85 Malaysian Population and Family Survey revealed that they were influenced by the new population policy to desire more children than they had originally wanted. These women were more likely to be rural Malays from the lower socioeconomic class. Ideal family size was more than four children. Children are desired for economic benefits and emotional support. The natality of the Malays has risen since 1980: their total fertility rate has increased while their contraceptive prevalence rate has dropped sharply. Coupled with a decline in the crude death rate, the present fertility preferences and behaviour of the Malays will render the target of the population policy more attainable than is reflected by the survey data. PMID- 2250039 TI - A comparison of different sources of information about pregnancy and childbirth. AB - Different methods of obtaining information in medical and social research present problems of interpretation for the researcher. However, there are few systematic studies on the extent of the lack of concordance yielded by different methods. This paper uses data from a randomized controlled trial of social support in pregnancy to examine this issue in relation to three methods of data collection- medical records, home interviews and a postal questionnaire--on the following topics: obstetric history; smoking, alcohol use, number of antenatal hospital visits, bleeding and depression in pregnancy; length of labour; baby's sex, birthweight and neonatal health problems; and ethnicity. Considerable discrepancies are found comparing the different data sources. These suggest that mothers may be more reliable sources of information than medical records, and that the anonymity of a postal questionnaire may provide higher estimates than home interviews on some sensitive topics, such as smoking in pregnancy. PMID- 2250040 TI - Constraints on weaning: evidence from Ethiopia and Sudan. AB - Evidence on infant weaning processes provided by field research in Addis Ababa, Ethiopia, and among a refugee population of Eritreans in the Sudan is presented. The study in Addis Ababa, where households were economically disadvantaged but the situation was nutritionally stable, allowed the identification of factors constraining weaning, which includes both the introduction of supplementary foods and the termination of breast-feeding. While the timing of each aspect of weaning was the outcome of the interaction between mother and infant factors, 'infant centred' factors were more important in the commencement and 'mother-centred' factors in the completion of weaning. The refugee population had in normal times a similar weaning regime, but under the unstable conditions of flight and life in a refugee camp the process had been significantly altered. Investigation of the factors which have led to altered weaning processes elaborates and confirms the model derived from the Addis Ababa study. PMID- 2250037 TI - Divorce in contemporary Japan. AB - Data from the 1985-86 Japanese census are analysed to explore the determinants of the divorce rates in Japan's forty-seven prefectures, using two theoretical models: (a) the social integration model, which is shown to have a greater utility in predicting Japanese divorce levels than (b), the human capital model. Female emigration patterns play a significant role in affecting the divorce rate. Population increase and net household income are also important predictors of the Japanese divorce rate and urbanization has a great influence in modern Japan. Demographic and aggregate variables such as migration, urbanization, and socioeconomic factors are useful when organized under a social integration model. PMID- 2250041 TI - Reproductive pattern in a rural Mediterranean population: La Alpujarra, Spain. AB - The reproductive pattern of a sample of nuclear families from La Alpujarra (Andalusia, Spain) is analysed. The origin of the wife or consanguinity of the couple does not influence fertility. Variability in number of pregnancies is most closely associated with marriage duration followed by the wife's year of birth. Differences in the number of births are explained more by the number of pregnancies than by the number of miscarriages. The number of survivors to the first birthday is dependent on the number of births and to a lower extent on infant mortality. Data from incomplete families show that reproductive performance of the wife below the age of 45 cannot be accepted as a reliable estimate of complete reproduction. PMID- 2250042 TI - Socioeconomic structure and fertility in China: a county level investigation. AB - Analysis of the general fertility rate in the counties of China shows significant associations with infant mortality, illiteracy, and the percentage of the population employed in industry, but not with industrial or agricultural output. Urban counties differ from rural in the importance of the illiteracy rate. The associations in the rural counties vary according to the region of China in which they are located. PMID- 2250043 TI - The sex ratios of offspring of sexually promiscuous people: with reference to hepatitis B and prostatic cancer. A comment. PMID- 2250044 TI - Monoclonal antibody 425 inhibits growth stimulation of carcinoma cells by exogenous EGF and tumor-derived EGF/TGF-alpha. AB - Carcinoma cells frequently coexpress transforming growth factor (TGF)-alpha and its receptor, the epidermal growth factor (EGF) receptor, implicating an autocrine function of carcinoma-derived TGF-alpha. Using a monoclonal antibody (425) to the EGF-receptor, we investigated the role of exogenous and tumor cell derived EGF/TGF-alpha mitogenic activities in proliferation of cell lines derived from solid tumors. Monoclonal antibody 425 was chosen for these studies because it inhibits binding of EGF/TGF-alpha to the EGF-receptor and effectively blocks activation of the EGF-receptor by EGF/TGF-alpha. Seven malignant cell lines originating from carcinomas of colon, pancreas, breast, squamous epithelia, and bladder expressed surface EGF-receptor and secreted EGF/TGF-alpha-like mitogenic activities into their tissue culture media. All cell lines were maintained in a defined medium free of exogenous EGF/TGF-alpha. EGF and TGF-alpha added to the culture medium stimulated proliferation of five cell lines to comparable levels. EGF/TGF-alpha-dependent proliferation was significantly reduced by addition of MAb 425 to culture media. In addition, monoclonal antibody 425 reduced proliferation of the five EGF/TGF-alpha responsive cell lines in the absence of exogenous EGF/TGF-alpha. Antiproliferative effects induced by monoclonal antibody 425 were reversible and could be overcome by addition of EGF to culture media. Our results indicate that tumor-derived EGF-receptor-reactive mitogens can promote proliferation of carcinoma cells in an autocrine fashion. PMID- 2250047 TI - Honor volume on the occasion of the 60th birthday of J. Calvin Giddings. PMID- 2250048 TI - Pesticide analysis by gas chromatography with a novel atomic emission detector. AB - An atomic emission detector, consisting of a microwave-induced helium plasma and atomic emission spectrometer, has been used for the gas chromatographic analysis of pesticides. In principle, it is possible to detect any element in the periodic table (except helium) which can elute from a gas chromatograph. Detection limits for C, H, D, N, O, Br, Cl, F, S, Si, P, Sn and Hg were found to range from 0.1 to 75 pg/s with selectivities over carbon of 5000 or more. The gas chromatography atomic emission detection system has been used for the detection and elemental characterization of 27 different pesticides by obtaining element-specific chromatograms for C, H, N, O, Br, Cl, F, P and S. By performing quantitative analysis for each element, it was possible to calculate the approximate empirical formulas for 20 different herbicides in two different mixtures. An extract from an apple doped with three pesticides was analyzed by gas chromatography-atomic emission detection. PMID- 2250046 TI - Alteration of lacto-series glycolipid glycosyltransferase activities in human colonic adenocarcinoma DLD-1 cells after culture in N,N-dimethylformamide containing medium. AB - Human colonic adenocarcinoma DLD-1 cells were grown under conditions which induce characteristics of differentiated cells using medium containing 0.8% N,N dimethylformamide in order to study alterations in glycosphingolipid glycosyltransferase activities during this process. Analysis of biosynthetic reactions involved in lacto-series antigen synthesis revealed no changes in the specific activities of either beta 1----4galactosyltransferase or alpha 1--- 3/4fucosyltransferase with N,N-dimethylformamide treatment. However, a dramatic decrease of from 14- to 20-fold in the beta 1----3N-acetylglucosaminyltransferase activity was observed in the treated cells. This enzyme catalyzes the rate limiting step in lacto-series core chain synthesis. This is consistent with the pattern of regulation of lacto-series antigen expression found to occur during oncogenesis in human colonic mucosa (Holmes EH, Hakomori S, Ostrander GK: J Biol Chem 262:15649, 1987). Total glycolipids from untreated and N,N-dimethylformamide treated cells were isolated and subjected to TLC immunostain analysis and solid phase radioimmunoassay with a series of monoclonal antibodies specific for lacto series-based carbohydrate antigens. A decrease of about 2-fold or less in the quantity of lacto-series antigens was observed as a consequence of N,N dimethylformamide treatment in both neutral glycolipid and ganglioside fractions. The results suggest that only very low levels of beta 1----3N acetylglucosaminyltransferase activity are required for the steady state expression of significant levels of lacto-series based glycolipids and that modulation of its activity levels by N,N-dimethylformamide treatment in DLD-1 cells represents a convenient in vitro system for studying aspects of regulation of lacto-series antigen expression. PMID- 2250045 TI - Gene expression during endochondral bone development: evidence for coordinate expression of transforming growth factor beta 1 and collagen type I. AB - Subcutaneous implantation of demineralized bone particles (DBP) into rats induces the formation of a bone ossicle by a tightly controlled sequence of chondro- and osteo-inductive events which are directly comparable to those which occur in normal endochondral bone development. Although the morphological and biochemical sequence associated with endochondral bone formation in this model has been well characterized, to date little information is available as to the gene regulation by which these events occur. To examine the expression of genes in this system, RNA was isolated from implants every 2 days over a time course spanning 3 to 19 days after implantation of DBP into rats. Cellular levels of mRNA transcripts of cell-growth-regulated and tissue-specific genes were examined by slot blot analysis and compared to the morphological changes occurring during formation of the ossicle. Analysis of the mRNA levels of histone H4 and c-myc, markers of proliferative activity, revealed several periods of actively proliferating cells, corresponding to 1) production of fibroprogenitor cells (day 3), 2) onset of bone formation (day 9), and 3) formation of bone marrow (day 19). The mRNA levels of collagen type II, a phenotypic marker of cartilage, peaked between days 7 and 9 post-implantation, corresponding to the appearance of chondrocytes in the implant, and rapidly declined on day 11 (to 5% of maximum value) when bone formation was observed. The peak mRNA levels of collagen type I, found in fibroblasts and osteoblasts, occurred first with the onset of bone formation (days 7-10) and again during formation of bone marrow (day 19). This study has demonstrated that the temporal patterns of mRNA expression of cartilage type II and bone type I collagens coincide with the morphological sequence in this model of endochondral bone formation. Further, the mRNA levels of transforming growth factor beta 1 (TGF beta) were compared to those of collagen types I and II; a direct temporal correlation of TGF beta mRNA levels with that of collagen type I was found throughout the developmental time course. This observation of a tightly coupled relationship between TGF beta and type I collagen mRNA levels is consistent with a functional role for TGF beta in extracellular matrix production during in vivo bone formation. PMID- 2250050 TI - High-performance liquid chromatography of amino acids, peptides and proteins. C. Characterisation of coulombic interactive regions on hen lysozyme by high performance liquid anion-exchange chromatography and computer graphic analysis. AB - The molecular characteristics of the dominant anion-exchange binding site of hen egg white lysozyme (HEWL) has been investigated using a combination of high performance liquid chromatographic techniques and computer graphic analysis of the X-ray crystallographic structure. These studies have indicated that the site of highest electrostatic potential, in terms of the density of negatively charged amino acid side chains, is located around the catalytic cleft area. The four residues tentatively identified to be involved in the electrostatic binding domain were aspartic acid 48, 52, 101 and glutamic acid 35. The number of these charged groups correlated with the maximum value of the chromatographically determined retention parameter (Zc value). Variations in the range of experimental Zc values obtained under different elution conditions have been interpreted in terms of conformational flexibility of the structural domains of HEWL which result in the opening or closure of the catalytic cleft during the retention process. PMID- 2250049 TI - Isolation and purification of lecithin by preparative high-performance liquid chromatography. AB - Mixed-chain, multispecies, egg yolk-derived lecithin was isolated and purified on a silica column with isocratic elution. A method development column (20 x 0.46 cm I.D.) packed with YMC 15-30 microns, 120 A spherical silica and a mobile phase consisting of 5 mM ammonium acetate in acetonitrile-2-propanol-methanol-water (80:13:5:12) was used to separate the lecithin from other phospholipids. The mobile phase conditions for the method development system was adopted for two types of preparative HPLC systems: a Separations Technology SepTech NovaPrep 5000 system with a 20 x 1.93 cm I.D. column and a ST/800A system with a 20 x 5.00 cm I.D. Annular Expansion (A/E) column. The maximum load was 50 microliters of crude solution (2 mg) for the method development column, 0.90 ml (35 mg) for the 20 x 1.93 cm I.D. column and 6.0 ml (240 mg) for the 20 x 5.00 cm I.D. A/E column. The flow-rates were 2, 35 and 235 ml/min, respectively. The fractions collected from the preparative systems were analyzed for purity by analytical-scale high performance liquid chromatography and by thin-layer chromatography with selective detection with molybdenum blue for phospholipids and detection of all organic compounds by sulfuric acid. Purity of the recovered lecithin was greater than 99%. PMID- 2250051 TI - Particle characterization in centrifugal fields. Comparison between ultracentrifugation and sedimentation field-flow fractionation. AB - A ten-component mixture of polystyrene latex particles in the 67-1220 nm size range was subjected to analysis by analytical ultracentrifugation (AUC) and sedimentation field-flow fractionation (SdFFF) using programmed and constant fields. The AUC analysis of the mixture yielded diameter values in good agreement with data determined on the separate components; the relative amounts of each component in the mixture were likewise closely reproducing the sample's known composition. Diameters determined by SdFFF, either in a constant- or programmed field mode, were in good agreement with the AUC for particles smaller than about 500 nm. For the sample's larger components, however, particularly the programmed mode showed diameter values smaller than expected. In addition, field programming resulted in incomplete recoveries of the larger particles, leading to more or less distorted mass distributions for the complex sample. The observed discrepancies, which are thought to result from events at the analytical wall in the FFF channel, suggested a protocol for accurate sizing, as opposed to fingerprinting, of samples with broad size distribution. By tracking sizes and amounts of the different components at different but constant field strengths, and retaining as analytically valid only those data recorded in a retention range from five to about thirty column volumes, it was possible to determine sizes and amounts in good agreement with known parameters for the sample. Unlike the AUC procedure, SdFFF produces fractions of a high degree of uniformity, which lend themselves to a secondary analysis, e.g. by electron microscopy, as shown in the study. PMID- 2250052 TI - Evaluation of pinched inlet channel for stopless flow injection in steric field flow fractionation. AB - In this article the concept of utilizing a pinched inlet channel for field-flow fractionation (FFF), in which the channel thickness is reduced over a substantial inlet segment to reduce relaxation effects and avoid stopflow, is evaluated for steric FFF using one conventional channel and two pinched inlet channels. It is shown that with the proper adjustment of flow-rate, the stopflow process in FFF can be completely avoided, thus bypassing the flow interruption associated with stopflow and reducing separation time. The maximum flow-rate that can be used for stopless flow operation without incurring zone distortion is shown to agree reasonably well with simple theory; slight departures from theory are attributed to the existence of reduced transport rates of large particles through thin channel structures. PMID- 2250053 TI - Malunited forearm fractures in children. AB - From 1971 to 1986, 80 skeletally immature patients with severe diaphyseal both bone forearm fractures were treated at Orlando Regional Medical Center. Greenstick, Monteggia, and Galeazzi fractures were excluded. Seventy-nine fractures were managed by closed means. When anatomic reduction could not be obtained, the best position was accepted. There were 47 patients with malunions of whom 39 returned for follow-up evaluation greater than 2 years after injury. They form the basis of this study. There were no delayed unions or nonunions in the entire group. Average follow-up in the group reported was 5 years 9 months (range 2 years to 13 years 10 months). All patients were satisfied with their functional and cosmetic results regardless of age, angulation, complete displacement, or loss of radial bow at time of union. Only nine patients had loss of motion. By our criteria, 36 patients (92%) had good or excellent results, with 32 excellent and four good results. Three patients (8%) had fair results, and there were no poor results. Age at time of injury did not correlate with recovery of motion. Distal fractures were found to have a better prognosis than proximal fractures. Based on the results of this study, closed reduction is the treatment of choice for skeletally immature patients with diaphyseal fractures of the radius and ulna. PMID- 2250055 TI - Premature closure of the physis following diaphyseal fractures. AB - Three patients who experienced premature complete physeal closure of the ipsilateral limb following diaphyseal fractures are reported. The diagnosis was recognized because of unexpected progressive limb length discrepancy following fracture healing. The cause is unknown. This phenomenon should be recognized by those treating fractures in children. PMID- 2250054 TI - Distribution of physeal and nonphyseal fractures in 2,650 long-bone fractures in children aged 0-16 years. AB - The distribution of 2,650 long-bone fractures in children is presented. Fractures involving the humerus, radius, ulna, femur, tibia, and fibula were classified according to Salter and Harris. Growth plate injuries accounted for 30% of fractures. Nonphyseal fractures occurred twice as often in the upper extremity as in the lower extremity. Girls with physeal fractures on the average were 1.5 years younger than boys with the same type of fracture in the same location. PMID- 2250057 TI - Diagnostic evaluation of patients with histiocytosis X. AB - The natural history of histiocytosis X was reviewed in 52 patients to identify the characteristics of patients with localized versus disseminated disease. Two categories of patients were identified. Older patients with solitary or multiple bone lesions constituted a low-risk group. This group had a high rate of development of new bone lesions (55% were asymptomatic) but an excellent prognosis. Patients with soft tissue involvement constituted a group at high risk for disease progression and organ dysfunction. These patients required a more extensive diagnostic workup and systemic treatment. A diagnostic algorithm is proposed to identify these two groups. PMID- 2250056 TI - Avulsion fractures of the patella. AB - Forty-seven skeletally immature patients with marginal fractures of the patella were evaluated. We showed that avulsion fractures may affect the superior, inferior, and medial margins of the patella, separating through the subchondral bone along the biomechanically susceptible margin of progressive chondroosseous transformation and expansion of the ossification center. In children, the small size of the osseous fragment may belie the actual size of the more peripheral, radiolucent cartilaginous component. Treatment may be either conservative or operative, depending on the extent of separation of the fragments and the functional capacity of the patellar/quadriceps mechanism. PMID- 2250059 TI - Autologous blood transfusions in children and young adults with low body weight undergoing spinal surgery. AB - The perioperative course of 118 patients weighing less than 45.5 kg (100.1 pounds) who participated in a predeposited autologous blood program from 1979 1984 is reviewed. Average age was 13 years 11 months (range 6 years 4 months to 20 years 4 months) and the average weight, 41 kg (range 30-45.4 kg). All underwent spinal surgery, 96% for scoliosis. The program involved preoperative donation of blood that was stored and subsequently retransfused to replace operative blood losses. Patients donated an average of 811 ml (range 208-1,320 ml) blood. Operation and hospitalization were completed by 63% without receiving any homologous blood, and the need for donor blood was reduced in the remaining 37%. Preoperative blood donation and retransfusion led to no significant complications. We describe an autologous blood transfusion program and show that autotransfusion is a safe and preferred method of blood replacement for children and young adults with low body weight undergoing elective surgery. PMID- 2250060 TI - Results of surgical treatment of muscular torticollis for patients greater than 6 years of age. AB - From 1983-1989, 37 patients with muscular torticollis were treated surgically by partial resection of the distal portion of the sternocleidomastoid muscle. Of these, 19 patients who at surgery were greater than 6 years of age (average 11 years 2 months) were followed for greater than 1 year (average 2 years 2 months). Although both function and cosmesis were improved in all cases, scoliosis was a residual deformity in some cases, especially in girls. PMID- 2250062 TI - Failures of pin removal after in situ pinning of slipped capital femoral epiphyses: a comparison of different pin types. AB - We reviewed 75 pin retrievals after in situ pinning of 35 children with slipped capital femoral epiphysis (SCFE). Four types of pins were used. Ten pins in 8 hips could not be removed because of pin breakage or stripping. Our failure rate was significantly related to pin type and size (p less than 0.039). As compared with the expected values using the chi-square method of analysis, the noncannulated large steel pins and cannulated steel pin groups had fewer failures (p less than 0.001) as compared with the cannulated titanium and noncannulated small steel pin groups. We now avoid using cannulated titanium or noncannulated small pins in treatment of SCFE. PMID- 2250058 TI - Simultaneous correction of pelvic obliquity, frontal plane, and sagittal plane deformities in neuromuscular scoliosis using a unit rod with segmental sublaminar wires: a preliminary report. AB - Ten patients with neuromuscular scoliosis and pelvic obliquity had segmental spinal instrumentation using a unit Luque rod with sublaminar wires and fixation into the pelvis. Nine of the 10 patients also had anterior spinal fusion without instrumentation before the posterior procedure. Average preoperative pelvic obliquity was 42 degrees which was corrected to 6 degrees (82% correction). Average preoperative scoliosis was 92 degrees, which was corrected to 16 degrees (81% correction). Complications included a wound hematoma in one patient and a superficial wound dehiscence in another. There have been no pseudarthroses or hardware failures to date. Excellent correction of the pelvic obliquity and the spinal curve in neuromuscular scoliosis can be obtained with use of a unit rod and without use of anterior instrumentation. PMID- 2250061 TI - Stickler syndrome. AB - Stickler syndrome is an autosomal-dominant disorder of connective tissue characterized by skeletal, orofacial, and ocular abnormalities. The most common specific roentgenographic findings include coxa valga and widening of the femoral neck. Acetabular protrusio, chondrolysis, avascular necrosis, and vertebral changes have also been described. Premature arthritic changes are to be expected. Congenital myopia and micrognathia are the most common nonskeletal findings. This syndrome should be considered when patients have unexplained coxa valga, especially with concomitant acetabular protrusio. PMID- 2250063 TI - Partial physeal growth arrest: treatment by bridge resection and fat interposition. AB - Twenty-eight skeletally immature patients underwent 29 primary physeal bridge resections at Children's Hospital and Medical Center in Seattle, Washington. Twenty-two resections were followed for 2 years. There were 11 excellent, five good, two fair, and four poor results. Overall mean growth was 83% with 98% in the excellent group and 96% in the good group. Physeal bridge resection is an effective method of treating partial physeal growth arrest. Results with fat compare favorably with results of other interposition materials without the disadvantages of local reaction and implant removal. PMID- 2250064 TI - Late diagnosis of hip dislocation in infants. AB - To determine the rate of late diagnosis of hip dislocations in infants, 26,455 newborns were examined by or under the supervision of the authors from 1976 to 1988. The incidence of examinations positive for dislocated or dislocatable hips was 3.8/1,000. The incidence of known late cases was 4/26,455 (0.2/1,000). Because follow-up of all initial examinations was not possible, this rate is probably artificially low. Hip screening programs with direct pediatric orthopaedic supervision can be successful, but late cases will still occur. PMID- 2250065 TI - Comparing the rate of femoral head necrosis of two different treatments of congenital dislocation of the hip. AB - We examined 120 patients with 140 congenital dislocations of the hip joint for femoral head necrosis. Of these, 77 hips were reduced with a Hoffmann-Daimler brace and the patients were subsequently placed in a spica cast in Lange position after a period in the Lorenz position. The hips of 43 patients were reduced the same way but were retained in a spica as described by Fettweis. The Lorenz group showed 10 grade II and III femoral head necroses, whereas there was only one grade III necrosis in the Fettweis group. The results were compared with the collected statistics of the German survey of congenital dislocation of the hip. PMID- 2250067 TI - Pyomyositis in an HIV-positive premature infant: case report and review of the literature. AB - Pyomyositis is a purulent infection of skeletal muscle caused predominantly by Staphylococcus aureus. Although not often encountered in the continental United States, pyomyositis is frequently seen in tropical areas. Pyomyositis is difficult to diagnose as it may mimic other diseases. Delay in diagnosis may lead to septicemia, shock, and death. Recently, two cases of patients with pyomyositis and acquired immune deficiency syndrome were reported. We report a case of pyomyositis in a 7-week-old premature infant who subsequently tested positive for anti-HIV antibodies. A brief review of the topic is included. PMID- 2250068 TI - Idiopathic extension contracture of the cervical spine: a report of two cases. AB - Two cases of a previously undescribed condition are reported. Both patients had an extension contracture of the cervical spine, secondary to a tight ligamentum nuchae. This condition has not been described in patients without an underlying disease process. PMID- 2250066 TI - Treatment of congenital pseudarthrosis of the tibia by the Ilizarov method. AB - Three cases of congenital pseudarthrosis were treated by the Ilizarov method. Consolidation was obtained by 3.5 months in three patients who had undergone several previous surgical procedures. Although the length of follow-up was short (maximum 3.5 years), consolidation occurred more quickly than by traditional methods. This technique also permitted both simultaneous correction of axial malalignment and leg lengthening. We think that this method has a place as a salvage procedure except where the distal fragment is very thin or dystrophic. PMID- 2250070 TI - Magnetic resonance imaging of an osteoid osteoma of the proximal femur: a potentially confusing appearance. AB - Osteoid osteomas are common benign pediatric bone tumors. However, radiographic diagnosis and location of the tumor nidus can be difficult. We recently diagnosed and treated an osteoid osteoma of the right proximal femur in a 9-year-old girl in whom the preoperative magnetic resonance images demonstrated a well-marginated lesion in the medullary canal but no tumor nidus. This was confusing and misleading. Correct diagnosis was made with a computed tomography (CT) scan. Care must be taken in interpretation of magnetic resonance imaging (MRI) in disorders in which secondary bone marrow changes occur to avoid erroneous diagnoses and possible incorrect operative procedures. PMID- 2250069 TI - Osteochondritis of the first metatarsal epiphysis. AB - Two cases of painful osteochondritis of the basal epiphysis of the first metatarsal are described. Complete resolution without deformity was achieved in both patients. We suggest that this condition be considered in the differential diagnosis of transitory foot pain in childhood. PMID- 2250071 TI - Surgical correction of congenital thoracic lordosis. AB - A 13-year-old girl with rigid congenital thoracic lordosis and congenital scoliosis was treated by a three-stage procedure of anterior transthoracic closing wedge osteotomies, posterior osteotomies of the laminar synostosis, correction of the deformity by sublaminar wires pulled back to a kyphotic bent Luque rod, and a later "pulling-out" procedure on the lateral chest wall. PMID- 2250072 TI - Epiphysiodesis: two-year clinical results using a new technique. AB - A new technique for epiphysiodesis was used to treat seven children with lower limb length discrepancies. A low-speed, high-torque drill was used to ablate the epiphyseal plate through a 1-cm incision under image intensification control. Roentgenographically, the physes appeared to be fused as early as 1 month postoperatively. Clinically, growth was arrested at the time of the operation because the discrepancy never became greater than it was at the time of surgery and improved in all cases at subsequent follow-up visits. No failures of fusion, post-operative infections, restricted joint motion, or angular deformities were encountered. PMID- 2250073 TI - Periodontal conditions in a group of Swedish adolescents. (I). A descriptive epidemiologic study. AB - The aim of the present study was to describe, clinically and radiographically, the periodontal conditions in 16- and 18-year-old adolescents from Northern Sweden. The studied samples comprised 287 16-year-olds and 283 18-year-olds. The clinical examination included recording of presence of plaque, bleeding on probing and calculus, and measurements of attachment level and pocket depth. Alveolar bone level was measured on bite-wing radiographs. A history was taken of the individual's occupation, oral hygiene habits and tobacco use, health, medication and previous orthodontic treatment. The prevalence of attachment loss (AL) was 9.4% in the 16-year-olds and 19.4% in the 18-year-olds. Proximal AL was found in 2.8% and 4.9%, respectively, and proximal bone loss in 1% in both groups. With only a few exceptions (3 individuals out of 82), the individuals with AL had their loss either at buccal/lingual surfaces or at proximal surfaces. Calculus was present in 32.7% of the 16-year-olds and in 44.9% of the 18-year olds. Pocket greater than 3 mm were found in 4%. No significant differences concerning the periodontal status or presence of plaque and calculus were detected between urban and rural groups or between sexes. Toothbrushing 2 or more times/day was performed by 84.3% of the 16-year-olds and by 83.7% of the 18-year olds. PMID- 2250074 TI - Periodontal conditions in a group of Swedish adolescents. (II). Analysis of data. AB - Periodontal conditions in adolescents from the north of Sweden have been described in an earlier study. 2 groups were distinguished, one with proximal and the other with buccal/lingual probing attachment loss (AL). The present study analysed the relationship between AL and various background variables: plaque, bleeding, calculus, pocket depth, toothbrushing, experience of fixed orthodontic appliance, general disease, socio-economic level. No significant differences between the total group with AL and that without AL were seen concerning general disease, socio-economic level, experience of orthodontic treatment, or presence of bleeding, plaque or calculus. When groups with AL on proximal surfaces and on buccal/lingual surfaces were analysed separately, it was found that the group with proximal AL more often had plaque, bleeding, calculus and pocket depths greater than or equal to 4 mm than the group with absence of AL and the group with buccal/lingual AL. In the latter group, toothbrushing was more frequent. The differences seen between the group with proximal AL and that with buccal/lingual AL may indicate different etiologies of loss of tooth support in these ages. PMID- 2250075 TI - Clearance of a topically applied fluorescein gel from periodontal pockets. AB - The clearance of a fluorescein gel applied with an irrigation technique in periodontal pockets was studied. In order to evaluate the time a drug remains in a periodontal pocket, the alteration in concentration of this drug in a given time period was investigated. After application of the gel in 4 pockets of 10 patients, samples were taken from 1 of the 4 pockets at 5, 10, 20 and 40 min. The results show that in the 1st phase, directly after application, most of the gel disappeared from the pocket, while in the 2nd phase, the fluorescein gel is washed out with a calculated 50% reduction time of 12.5 min. The rapid clearance of the gel observed after irrigation might provide a partial explanation of the minor effect of pocket irrigation on the subgingival microflora. PMID- 2250076 TI - Tissue regeneration principles applied to separation of fused teeth. AB - A two-step surgical procedure for separating a central incisor fused to a supernumerary tooth with a 4-year follow-up is described. The fusion was between the crowns and 3/4 of the root length. The roots were connected by web-like radio opaque tissue. The periodontal ligament could be followed along the lateral aspect of the roots and was continuous along the base of the web. In the first surgical phase, a full-thickness semilunar flap was raised; a fissure bar was cut along and through the web up to the approximate location of the junctional epithelium and the flap was sutured. It was assumed that cells from the bone surrounding the web and/or connective tissue cells from the flap had migrated into contact with the web hard tissue. This resulted in replacement resorption of the web. The connective tissue replacing the web acted as a septum separating the 2 parts of the root. The distal root was extracted. Resorption continued until most of the web disappeared from the wound. At this point, the remaining layer of web tissue was thin enough to allow repopulation of the resorbed surface with periodontal cells from the buccal and palatal sides of the web. The successful clinical outcome supports the assumption that new attachment consisting of periodontal ligament and cementum was formed following the 2-step surgical procedure. Application of the technique is limited by the width of the fusion rather than by its length. PMID- 2250077 TI - Periodontal bone loss in the aging beagle dog. A radiographic study. AB - Studies in the beagle dog have clearly established the usefulness of this breed in periodontal disease research. However, little is known about the progressive nature of the disease with advancing age. It is the purpose of this paper to describe frequency and distribution of radiographically detectable lesions in an aging population of 166 colony dogs. 3 grades of alveolar bone loss were determined on high-quality postmortem radiographs. The number of teeth involved was similar in male and female and was age-dependent. Disease was more frequent in the maxillary arcades, with the 2nd upper premolar most frequently involved. Most extensive bone loss was noted around the 3rd and 4th upper premolars, and 1st and 2nd lower molars. It is felt that by the study of such a large group of older colony dogs, a better understanding can be gained of the expected alveolar bone loss with age as determined radiographically. PMID- 2250079 TI - An association between long-term non-steroidal anti-inflammatory drug therapy and the severity of periodontal disease. AB - The present study was undertaken to compare the periodontal status of a group of 50 patients on long-term non-steroidal anti-inflammatory drug (NSAID) therapy with that of an age and sex-matched group of 42 controls. The mean duration of drug therapy in the study group was 9 years (range 2-30 years). The clinical parameters investigated were plaque index (PI), gingival index (GI), pocket probing depth (PPD), loss of attachment (LOA), gingival recession (GR) and gingival fluid flow (GFF). Long cone periapical radiographs were also taken to score the amount of alveolar bone resorption. Examinations were carried out on 6 Ramfjord teeth in each subject. The results showed that there were no significant differences between the groups for PI, GI, PPD, LOA, GR or alveolar bone resorption. However, a highly significant difference was seen between the gingival fluid flow in the study (16.74 +/- 10.61) and control (37.72 +/- 28.63) groups (p less than 0.001). It is suggested that this may be associated with the specific effects of NSAIDs in reducing the vascularity and permeability of small blood vessels. PMID- 2250078 TI - Evaluation of gingival suppuration and supragingival plaque following 4 modalities of periodontal therapy. AB - This study evaluated the effect of coronal scaling (CS), root planing (RP), modified Widman surgery (MW) and flap with osseous resectional surgery (FO) upon the presence of gingival suppuration and supragingival plaque. 75 patients completed split-mouth therapy and 2 years of maintenance care. Data were collected prior to the initiation of therapy, following initial therapy, following surgical therapy and yearly during 2 years of maintenance care. All 4 types of therapy reduced the prevalence of suppuration with RP, MW and FO producing a greater reduction than CS in sites greater than or equal to 5 mm. Sites were grouped according to presence of suppuration at 2 consecutive examinations. The mean changes in probing depth and probing attachment level for each time period were compared. Sites that began to suppurate between 2 exams or were suppurating at both exams had a less favorable response in mean probing depth reduction and mean probing attachment gain when compared to sites that stopped suppurating between exams or did not suppurate at either exam. The prevalence of supragingival plaque decreased during active therapy and 2 years of maintenance. There was no difference in the prevalence between the therapy groups except for FO-treated sites showing more plaque accumulation after surgical therapy. The presence or absence of supragingival plaque at specific sites was dynamic, frequently converting to a new status between 2 examinations. PMID- 2250080 TI - Actinobacillus actinomycetemcomitans and Bacteroides intermedius in human periodontitis: age relationship and mutual association. AB - This study examined age relationships and mutual interrelationships between cultivable Actinobacillus actinomycetemcomitans and Bacteroides intermedius in 1624 periodontitis patients, 15 to 89 years of age. Each subject contributed a pooled subgingival sample, obtained from 3 deep periodontal pockets with paper points. A. actinomycetemcomitans occurred with higher prevalence (74%) and mean recovery (7% in culture-positive patients) in patients less than 25 years old than in adult and geriatric patients (prevalence about 31%; mean recovery about 1%). The organism was detected in 85% of localized juvenile periodontitis patients. B. intermedius was recovered from 45% of the study subjects, averaged about 7% of total isolates in positive patients, and showed no predilection for any age group. As determined from predicted and observed values for A. actinomycetemcomitans and B. intermedius, occurring alone and in combination, no synergistic or antagonistic relationships between the organisms could be delineated with respect to subgingival colonization. The therapeutic implication of these findings is discussed. PMID- 2250081 TI - Evidence for rapid multipolar and slow unipolar production of human cellular and acellular cementum matrix with intrinsic fibers. AB - The genesis of root cementum has been studied infrequently in animal models, e.g., in mice, rats and dogs, but rarely in the human. The present study was based on 8 premolars (4 maxillary and 4 mandibular, 7 first and 1 second) selected from a large collection of freshly extracted human teeth. All teeth were free of disease and presented with roots developed to about 50-80% of their length. After decalcification in EDTA, the apical half of the roots was divided axially into mesial and distal portions. The latter were subdivided into 4 slices cut in the corono-apical direction. These slices were Epon-embedded and cut for examination in the light- and transmission electron microscope. It was found that 2 basically different modes of cementum matrix production occurred at or near the advancing root edge. These 2 modes, i.e., the multipolar versus unipolar matrix production, resulted in either cellular (CIFC) or acellular intrinsic fibre cementum (AIFC). Both varieties did not contain fibres of Sharpey and were restricted to regions of the root usually covered with cellular mixed stratified cementum (CMSC). By comparison with recently published data on the rate of cementum apposition, it is suggested that the multipolar mode is a rapid form, whereas the unipolar mode is a slow-rate form of producing intrinsic fibre cementum. PMID- 2250083 TI - Influence of test method on failure stress of brittle dental materials. AB - A bi-axial flexure test (piston-on-three-balls), a four-point flexure test, and a diametral tensile test were used to measure the failure stress of four brittle dental materials: zinc phosphate cement, body porcelain, opaque porcelain, and visible light-cured resin composite. Furthermore, the fracture probability of the bi-axial test specimens was predicted from the results of the four-point flexure test, with use of statistical fracture theory. Bi-axial failure stresses calculated from an equation developed by Marshall (1980) exhibited no significant difference for zinc phosphate cement as a function of piston size, specimen thickness, presence or absence of a stress-distributing film, and loading rate. The four-point flexure strength values of zinc phosphate cement and opaque procelain were significantly lower (p less than 0.05) than the corresponding mean bi-axial strength values, while the mean four-point flexure strength values of body porcelain and resin composite were not significantly lower (p greater than 0.05) than the corresponding mean bi-axial strength values. The diametral tensile strength of all materials was significantly lower than the bi-axial flexure strength. The mean bi-axial flexure strengths of zinc phosphate cement and opaque porcelain were much higher than the theoretical values predicted from surface flaw theory, while the strength values for body porcelain and resin composite were comparable with those determined from the four-point flexure test. These results demonstrate that the strength of zinc phosphate cement depends not only upon the geometric factors, but also upon sample preparation conditions. PMID- 2250085 TI - Influence of water exposure on the tensile strength of composites. AB - The objective of this study was to investigate whether water storage causes permanent damage to composites by determining how the tensile strength of nine different composite materials changes with both water storage and water storage followed by dehydration. Eighteen samples (ASTM-D Specification 1708-66) of each of the nine materials were prepared and divided into three groups of six samples each. Group I was stored dry at 60 degrees C, while Groups II and III were stored in distilled water at 60 degrees C. After six months, Groups I and II were subjected to tensile testing, while Group III was transferred to a desiccator and dehydrated for two weeks at 60 degrees C before this group was tested in tension. Mean values, pooled by storage group independent of material, revealed a significant (p less than 0.05) reduction in strength for both Groups II and III relative to Group I. These findings prove that water has an irreversible effect on most dental composites. A comparison of Group II with Group III data revealed that the samples which were aged in water and tested (Group II) were significantly (p less than 0.05) weaker than the dehydrated samples (Group III). However, some products within Group III did not show any tendency to recover their strength after dehydration. PMID- 2250084 TI - Electrochemical impedance characterization of human and bovine enamel. AB - The alternating current impedance characteristics of human and bovine enamel slices were measured in vitro. An electrochemical cell containing two platinum gauze electrodes and 0.01 mol/L KCl buffered to pH 7.4 at 20 degrees C was used. The electrodes were attached to a potentiostat that was connected to a microcomputer-controlled frequency-response analyzer. Measurements were made at discrete frequencies between 1 Hz and 65 kHz by application of a sinusoidal potential of 50 mV (rms) across the assembled cell. The impedance was calculated from the input potential and the resulting measured flow of current. For quantitative evaluation of these measurements, an equivalent circuit was postulated. It contained five passive electronic components and accurately modeled the different specimens. Values for individual electrical components in the equivalent circuit were estimated by complex non-linear least-squares regression analysis. This study demonstrated that it is possible to measure and quantitatively distinguish between the impedance characteristics of: permanent human, deciduous human, and bovine enamel, as well as the enamel from a variety of sites from human teeth, some of which had been extracted prior to being fully erupted. Proposals are made as to which physical properties in the specimens are modeled by individual components in the equivalent circuit. PMID- 2250082 TI - The effect of tin on the corrosion behavior of the Ag-Hg phase of dental amalgam and dissolution of mercury. AB - The anodic polarization behavior of the Ag-Hg matrix phase of dental amalgam (gamma 1) and the rate of mercury dissolution were examined as a function of the tin content. The objectives were to determine the effect of tin on the electrochemical behavior and dissolution of mercury and to provide evidence on whether tin dissolves in the gamma 1 phase or precipitates as a tin-rich phase. Anodic polarization curves were recorded for specimens of the gamma 1 phase containing 0-1.5% Sn and for the gamma 2 phase and a gamma 2-containing dental amalgam, in synthetic saliva. Mercury dissolved in synthetic saliva in 24 h was determined for the gamma 1 phase containing 0-1.0% Sn, with cold-vapor Atomic Absorption Spectrophotometry used for mercury analysis. Tin induced passive behavior of the gamma 1 phase and suppressed mercury dissolution. The passive gamma 1 phase did not exhibit a breakdown of passivity occurring at the gamma 2 phase. The results were consistent with the tin presence in gamma 1 in a solid solution, rather than in tin-rich precipitates, and indicated that at least 1.5% Sn can be dissolved in gamma 1 at 37 degrees C. PMID- 2250086 TI - Expression of integrins in human gingiva. AB - The distribution of the alpha 1-alpha 6 subunits of beta 1 integrins was studied by using a panel of monoclonal antibodies in indirect immunofluorescence microscopy. The results showed that the beta 1 subunit was expressed at the cell membrane of basal cells of gingival epithelium, throughout the cells of junctional epithelium (JE), and in cells of connective tissue, including endothelial cells and, more faintly, in inflammatory cells in gingival connective tissue. The alpha 4 subunit was expressed selectively in inflammatory cells, and the alpha 5 subunit was expressed in cells throughout gingival connective tissue. An overall cell membrane immunoreactivity for the alpha 2 and alpha 3 subunits was shown in basal cells of gingival epithelium and in cells of JE, corresponding to the epithelial localization of the beta 1 subunit. The alpha 6 subunit was polarized to the basal aspects of basal epithelial cells, but was also present in an overall cell surface distribution in basal cells and in cells of JE. The beta 4 integrin subunit was mainly expressed at the basal aspects of basal cells in gingival epithelium and JE. The results indicate that the alpha 2/beta 1, alpha 3/beta 1, alpha 6/beta 1, and alpha 6/beta 4 integrins are all expressed in human gingival epithelium. Of these, the alpha 6/beta 4 integrin complex is the major candidate for mediation of the attachment of epithelial cells to the basement membrane facing the connective tissue and probably also the tooth. PMID- 2250088 TI - Fluoride intake of infants in New Zealand. AB - Since the fluoride (F-) intake of New Zealand infants and young children is not known, a study was designed to determine and compare the F- intake of infants, aged 11 to 13 months, residing in fluoridated (F) and non-fluoridated (NF) areas. Parents of 60 infants duplicated quantitatively and qualitatively all food and drink that the infants ingested during a three-day period. The acid-diffusible F- content in the liquid homogenate was isolated by the HMDS-HCl diffusion technique (Taves, 1968) and measured by a fluoride electrode. The ionic F- in samples of breast milk was measured directly by the electrode. In the F area, the F- content of the food and drinks of 31 subjects ranged from 0.130 to 0.679 mg/kg (mean, 0.320; SD, 0.168); in the NF areas, the F- content of the food and drinks of 29 subjects ranged from 0.036 to 0.281 mg/kg (mean, 0.095; SD, 0.053). The dietary intake ranged from 0.089 to 0.549 mg F/day (0.009-0.056 mg F/kg bw) in the F area, and from 0.038 to 0.314 mg F/day (0.004-0.038 mg F/kg bw) in the NF area. Including F- from tablets and toothpastes, total intake ranged from 0.093 to 1.299 mg F/day (0.009-0.150 mg F/kg bw) and from 0.039 to 0.720 mg F/day (0.004 0.061 mg F/kg bw) in F and NF areas, respectively. The mean dietary intake of infants in the F area was about half the recommended "optimal" range; in the NF areas, the dietary intake was five to seven times less than the optimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250087 TI - Wavelength-independent microradiography used for quantification of mineral changes in thin enamel and dentin samples with natural surfaces, pseudo-thick tooth sections, and whole teeth. AB - Tests of the efficacy of therapeutic agents for caries repair or prevention in vitro or in situ should be performed as realistically as possible. This implies the non-destructive assessment of mineral changes in whole teeth. In this study, Wavelength-independent Microradiography (WIM), a non-destructive form of microradiography that uses polychromatic x-rays, was tested for its use in following mineral changes during demineralization of whole teeth. Since the method was, in a previous paper, only tested on flat samples of about 0.3 mm in thickness, the present study aimed to adapt and test WIM for use on thicker samples. This was done in three steps: In the first step, natural surfaces were introduced. The mineral content of enamel and dentin samples about 0.3 mm in thickness and with natural (curved) surfaces was determined by WIM, and the result was compared with mineral measurements performed with Longitudinal Microradiography (LMR). A correlation of 0.98 was found for both the enamel and the dentin samples. In the second step, the thickness of whole teeth was added. Thick tooth sections were simulated by addition of a 5-mm block of dentin to such thin enamel and dentin samples. Mineral measurements with WIM of the samples plus the dentin block were compared with mineral measurements of the thin samples (without block). A correlation of 0.97 was found for enamel, and one of 0.90 was found for dentin. Finally, in a third step, the demineralization of whole premolars was followed as a function of time. PMID- 2250089 TI - Long-term effects of orthodontic forces on the morphology of the rat-incisor socket and its location in the mandible. AB - The effect of orthodontic force application on the rat-incisor socket and mandible was studied on roentgenograms. A mean linguo-intrusive force of 19 +/- 0.6 g was applied continuously to the shortened left lower incisor for a period of two (group A) and four weeks (group B). A third group of rats, subjected to shortening of the left mandibular incisor only, served as a hypofunctional control (group C). A fourth group of normal rats constituted the intact control (group D). After a recovery period of three months, the animals were killed, and standardized roentgenograms of the cleaned mandibles were taken. Socket and mandibular dimensions were measured on magnified tracings of the roentgenograms. Comparison of groups A and B with the control groups, on the one hand, and of group C with group D, on the other, facilitated isolation of the hypofunctional factor. In groups A and B, the orthodontic forces caused changes in the parameters affected (i.e., socket area, alveolar bone thickness, mandibular dimensions) and not affected by hypofunction (i.e., socket angulation and location, anterior-socket length). The former findings implies modification of the adaptive capability of dental structures to functional demands. It is concluded that mechanical loading of the incisor for two to four weeks causes long-lasting changes in the socket and its surrounding bone. PMID- 2250090 TI - Setting reactions and compressive strengths of calcium phosphate cements. AB - Setting reactions and compressive strengths of a self-hardening calcium phosphate cement (CPC) were investigated. The CPC consists of tetracalcium phosphate (TTCP) and anhydrous dicalcium phosphate (DCPA). The cement specimens were prepared by mixing 0.7 g of the powder (TTCP 72.9 wt% + DCPA 27.1 wt%) with 0.175 mL of the liquid (25 mmol/L H3PO4 and 1.32 mmol/L sodium fluoride). The specimens were removed from the molds at pre-determined time intervals after being mixed, and their compressive strengths were measured. Immediately afterward, the fractured specimens were rapidly frozen in ethanol (-80 degrees C), lyophilized, and examined by powder x-ray diffraction and scanning electron microscopy (SEM). The results showed that (1) hydroxyapatite was the only reaction product; (2) the reaction was nearly completed within four h, during which both the reaction product and compressive strength increased linearly with time, resulting in a strong correlation between the two; and (3) fully set CPC consisted primarily of small rod-like crystals and some platy crystals. PMID- 2250091 TI - The crown odontoblasts of rat molars from primary dentinogenesis to complete eruption. AB - The involution of crown odontoblasts after primary dentinogenesis in teeth of limited eruption is discussed. The odontoblasts of rat first lower molars were analyzed morphometrically from the tenth day to the 40th day of age, i.e., from the late phase of primary dentinogenesis to complete eruption. All the organelles underwent atrophy, but at different rates. In particular, the membranes of the endoplasmic reticulum decreased progressively in surface area from day 10 to day 40, whereas those of the Golgi apparatus decreased significantly between day 10 and day 14, and then remained practically unchanged in size. The volume of the lysosome compartment never increased beyond that during primary dentinogenesis. The profile length of the endoplasmic reticulum in each observed cell section was taken as an estimate of secretory activity. At day 40, this organelle was smaller in approximately 95% of the cells than it had been in any cell at day 10. These results suggest that cell atrophy may occur without any increase in the degradation processes of the cytoplasmic components and that the organelles along the secretory pathway may have independent regulatory systems. In the odontoblasts, as in several types of secretory epithelial cells, only a small fraction of the cells is engaged in appreciable secretory activity. This occurs, however, when the overall activity of the same cell population is relatively low. PMID- 2250092 TI - Performance indicators in research. PMID- 2250093 TI - Should 75% of IADR abstracts be rejected? PMID- 2250094 TI - Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. AB - This report describes the development of obesity syndromes in mice caused by two autosomal recessive mutations, fat (fat), located on chromosome 8, and tubby (tub), located on chromosome 7. Both mutations cause slowly developing but ultimately severe obesity conditions. Although hyperinsulinemia, hyperactivity of the beta cell of the islets of Langerhans, and beta-cell degranulation are consistent features, these obesity syndromes do not progress to severe diabetes. The many different single-gene mutations in the mouse that produce obesity diabetes syndromes of varying degrees of severity make the mutant mouse a powerful tool for analyzing the number and nature of the primary defects than can cause obesity states. PMID- 2250095 TI - Rheumatic fever susceptibility in four ascertainments: regressive segregation on a geometric ascertainment pattern. AB - On resolving the ascertainment biases of the observed data in the geometric continuum vaffected-1 x P(sibship), where 0 less than v----infinity, four published ascertainments of rheumatic fever show excellent conformation with Mendelian recessive segregation, even in multiplex sibships. In two surveys in which ascertainment bias is near or a little above random sampling (v = 1), this conclusion is further corroborated by classical segregation analysis. The other two surveys have bias trends declining (v less than 1) very much below random sampling. Such levels of ascertainment bias, if defined through the ascertainment probability parameter pi, would be out of range because the range is from single ascertainment, where pi----0 to random sampling where pi = 1 and probability cannot exceed unity. Highly successful antimicrobial measures that would reduce the number of diseased sibs independent of the distribution of susceptible sibs could produce a dissociation of the gene-to-"rheumatic" relationship and thus explains the declining ascertainment bias. PMID- 2250097 TI - A program for calculating Nei's genetic distances and their jackknifed confidence intervals. PMID- 2250096 TI - Characterization of heterochromatin by sequential counterstain-enhanced fluorescence in three domestic bird species: Meleagris gallopavo, Columba livia domestica, and Anser anser L. AB - The karyotypes of three avian species--Meleagris gallopavo, Anser anser L., and Columba livia domestica--were investigated by means of counterstain-enhanced fluorescence techniques (chromomycin A3/distamycin A/DAPI followed by DAPI/actinomycin D staining). A heterochromatin characterization of macro- and microchromosomes was performed. CMA3-positive (GC-rich) regions in the turkey included the telomeres of chromosomes 1, 3, 4, and Z. In the goose, the chromosome 2 was also CMA3-bright at the telomeres. The W chromosome possessed large amounts of CMA3-bright material on the short arm in both the turkey and the goose. Two types of centromeric heterochromatin were distinguished on acro- to telocentric chromosomes 6 to 14 in the pigeon. The microchromosomal heterochromation of the turkey and goose was GC-rich but had a high degree of variation. In the pigeon, several microchromosomes possessed predominantly AT rich heterochromatin. PMID- 2250098 TI - GENE-LINK: a program in PASCAL for backcross genetic analysis. PMID- 2250099 TI - Ascovirus infectivity and effects of infection on the growth and development of noctuid larvae. AB - The infectivity per os and by inoculation of ascoviruses isolated from Heliothis zea, Spodoptera frugiperda, and Trichopulsia ni and the effects of infection by these viruses on host growth and development were studied in the species from which these viruses were originally isolated, or in the case of the H. zea isolate, in H. virescens. Mortality caused by all three viral isolates averaged less than 15% in third instars fed doses of 10 to 10(5) viral vesicles per larva incorporated into diet, whereas inoculation with as few as 10 viral vesicles consistently yielded mortality rates greater than 90%. In tests where groups of 10 larvae were inoculated sequentially with a minuten pin that had been inserted into the hemocoel of an infected larva and then dried for up to 24 hr, mortality rates were consistently greater than 90%. The latter results suggest that ascoviruses in the field may be vectored by insect parasites. The studies of the effects of infection on larval growth and development demonstrated a marked loss of appetite and a decrease in weight gain within 24-48 hr of infection in all three isolates. Third instars inoculated at a weight of ca. 15 mg gained little weight after infection and had difficulty molting, but survived in an arrested state of development for 2-5 weeks. Controls pupated within 5-7 days after attaining weights, depending on the host species, in the range of 300-500 mg. Arrested development and lack of weight gain appear to be due to decreased feeding, whereas the long survival of infected larvae is likely due to the limited destruction of host tissues. PMID- 2250100 TI - Comparative histopathology of three ascovirus isolates in larval noctuids. AB - The histopathology caused by three ascoviruses isolated respectively from Heliothis zea, Spodoptera frugiperda, and Trichoplusia ni was studied in the host species from which the viruses were isolated originally, or in the case of the H. zea isolate, in H. virescens. In all three isolates, infected cells and virion containing vesicles in the hemolymph were observed by 3 days postinoculation. The isolates from H. zea and T. ni exhibited relatively broad tissue tropisms infecting the tracheal matrix, epidermis, and connective tissue, and in the latter isolate, the fat body. Although considered variants of the same virus, these isolates varied slightly in their tissue tropism in that the isolate from H. zea replicated more extensively in the epidermis. The isolate from T. ni replicated in the fat body during early stages of disease, but not in advanced stages, and was not as common in the epidermis as the isolate from H. zea. The isolate from S. frugiperda replicated only in the fat body and completely destroyed this tissue by 12 days postinoculation. The progression of disease within the tissues was correlated with a rise in the concentration of virion containing vesicles in the hemolymph of all three isolates. Vesicle concentrations rose from 10(7) on day 2 to 10(8)/ml of hemolymph on day 9, plateaued for 5-7 days, and then declined gradually through day 20. These results indicate that the chronic nature of the diseases caused by ascoviruses is due to the limited degree to which they infect major tissues (isolates from T. ni and H. zea) or the infection of tissues less essential to the maintenance of larval life (isolate from S. frugiperda). PMID- 2250101 TI - The fate of Bacillus thuringiensis var. israelensis in B. thuringiensis var. israelensis-killed pupae of Aedes aegypti. AB - Carcasses of mosquito larvae killed by Bacillus thuringiensis var. israelensis allow its complete growth cycle (germination, vegetative growth, and sporulation), thus becoming toxic themselves to scavenging larvae. In this study, we demonstrate that the bacterium is capable of inducing death of Aedes aegypti pupae and of recycling in the resulting carcasses. B. thuringiensis var. israelensis-killed pupae were obtained by treating 40-hr-old synchronized fourth instar larvae with a low dose of spores (8000/ml). The fraction of dead pupae was reduced by higher or lower spore concentrations as well as by treating younger or older larval populations (both fourth instar): Increased proportions of dead larvae were obtained at higher concentration or by earlier treatment, whereas lower concentrations or later treatment resulted in more living pupae. Multiplication of B. thuringiensis var. israelensis is shown to occur in the carcasses of dead pupae. The number of spores in each pupal carcass followed a similar kinetic as in larval carcasses, but the final yield was about 10-fold higher, apparently reflecting the difference in dry weight between the two mosquito developmental stages (426 micrograms vs 83 micrograms, respectively). The specific larvicidal activity in a homogenized dead pupa was similar to that of B. thuringiensis var. israelensis powder, LC50 of about 600 spores/ml. PMID- 2250102 TI - Ultrastructural changes in salivary glands of tsetse, Glossina morsitans morsitans, infected with virus and rickettsia-like organisms. AB - Electron microscope observations on enlarged hypertrophied salivary glands dissected from adult laboratory-reared male Glossina morsitans morsitans show a concurrent infection of the salivary gland tissue with rod-shaped virus particles and intracellular rickettsia-like organisms. The latter are found intracellular in the epithelium and in the gland lumen enclosed within lytic zones. The virus particles are found within the degenerating cytoplasm, nuclei, and lumen of the cell where they are especially numerous. Stratified epithelium and gland enlargement are a prominent feature of the infection. These observations suggest that biological associations between salivary gland tissue and diverse microbes may be more common than formerly recognized. The microbes appear to cause damage to salivary gland cells, causing hyperplasia which assumes pathologic proportions. PMID- 2250103 TI - A-431 cells and human keratinocytes synthesize and secrete the third component of complement. AB - Biosynthetic radiolabeling studies demonstrate that A-431 cells, a human epidermoid carcinoma cell line, and human keratinocytes synthesize and secrete C3 as two disulfide-linked polypeptide chains of 120 and 75 kD. Moreover, epithelial cell-derived C3 co-migrates in SDS-PAGE with that produced by HepG2 cells, a human hepatoma cell line previously used to elucidate complement component biosynthesis. Pulse-chase studies in A-431 cells demonstrate that epithelial cell derived C3 is produced as a 195-kD precursor molecule, pro-C3, which is processed intracellularly by limited proteolysis into 120- and 75-kD C3 alpha and beta chains. Comparative studies demonstrate that A-431 cell-derived C3 is synthesized, processed, and secreted in parallel but in lower quantity than that produced by HepG2 cells. Treatment of biosynthetically labeled A-431 cell culture supernatants with normal human serum and zymosan produces C3 alpha chain cleavage and specific C3 fragments that are not present in control culture supernatants treated with heat-inactivated human serum and zymosan. Northern blot analysis of total cellular RNA extracted from A-431 cells, human keratinocytes, and HepG2 cells reveals quantitative identity of a 5.1-kb C3 mRNA species in these three cell types. Epithelial cell-derived C3 may play an important role in local inflammatory and immunologic reactions including such reactions in human skin. Moreover, epithelial cell C3 synthesis may have direct relevance to the recent demonstration of C3d,g within selected normal primate epithelial basement membranes, including epidermal basement membrane. PMID- 2250104 TI - Basic fibroblast growth factor stimulation of epidermal wound healing in pigs. AB - Basic fibroblast growth factor (bFGF) has recently been shown to be a mitogen for keratinocytes. This observation has now been extended in a porcine model of epidermal wound healing. A single application of recombinant human bFGF given at the time of injury to healthy animals accelerated the rate of epithelialization by 20%; multiple applications gave no greater effect than the single application. Histologic analysis of biopsies of these partial-thickness wounds taken during bFGF-mediated healing supported the assessment of an enhanced rate of epithelialization and an earlier onset of dermal healing. Because no histologic abnormalities were observed, bFGF induced an acceleration of what appears to be the normal healing process. PMID- 2250105 TI - Depletion of alcohol (hexanol) dehydrogenase activity in the epidermis and jejunal mucosa in Sjogren-Larsson syndrome. AB - Using a histochemical technique, we have demonstrated a consistent deficiency of alcohol (hexanol) dehydrogenase activity within the epidermis and jejunal mucosa of patients with Sjogren-Larsson syndrome. Biochemical assay of the fatty alcohol: NAD oxidoreductase activity in cultured fibroblasts and leukocytes from these patients showed deficient activities compared with controls. The histochemical and biochemical results are complementary, and the simpler histochemical method can be used reliably for initial screening of patients with ichthyosis in whom a diagnosis of Sjogren-Larsson syndrome is suspected. PMID- 2250106 TI - Thermotolerance and the heat shock response in normal human keratinocytes in culture. AB - Protective responses of normal human epidermal keratinocytes in culture, after exposure to elevated temperatures ("heat shock"), were examined. Cell viability, measured 24-48 h after a 20-min heat challenge at temperatures between 37 degrees C and 54 degrees C, declined sharply within a narrow 2 degrees-3 degrees C range. However, conditioning with a mild thermal pretreatment (40 degrees C or 42 degrees C for 1 h) protected the keratinocytes against a subsequent heat challenge. This induced thermotolerance was apparent when cells were challenged at 1, 3, and 6 h after the thermal pre-treatment, but disappeared by 24 h. Heating conditions that induce thermotolerance also stimulated the synthesis of heat-shock proteins (hsp) in these cells. Inductions of prominent 35S-methionine labeled bands at 70, 78, and 90 kDa were observed. However, the increases in synthesis of these heat-shock proteins did not correlate well with thermotolerance, because large increases were also observed at certain elevated temperatures that did not produce improved survival. Keratins observed in these cells (50 and 58 kDa classes) were not induced by heat shock. The development of thermotolerance, and the induction of hsp, were both completely blocked by 3' deoxyadenosine (cordycepin), an inhibitor of newly synthesized messenger RNA, but not by adenosine, the normal analog. While heat-inducible mRNA apparently mediate some function important for the development of thermotolerance, the nature of that role remains speculative. Overall, our findings establish the existence of a functional thermal protective mechanism in human keratinocytes that appears to require the synthesis of new mRNA. PMID- 2250107 TI - IgG subclasses in the serum and skin in subacute cutaneous lupus erythematosus and neonatal lupus erythematosus. AB - IgG subclasses differ in their biologic and chemical properties, such as complement fixation, protein and cellular binding, and placental transfer. In this study, IgG subclasses of anti-Ro/SSA antibodies in subacute cutaneous lupus (SCLE) and neonatal lupus (NLE) are examined in the serum and in the skin. IgG subclasses in NLE beginning in utero (NLE-heart disease) are compared to subclasses in NLE beginning after birth (NLE-skin disease). Human skin was grafted onto athymic mice, mice were injected with one of eight anti-Ro/SSA maternal NLE sera (four heart block, four skin disease) or seven anti-Ro/SSA SCLE sera, and grafts were examined for IgG subclasses using monoclonal anti-human IgG subclass reagents in an immunofluorescent technique. Lesional skin was examined from four SCLE patients. IgG1 was the only IgG subclass detected in the grafts and skin lesions. IgG1 was the predominant anti-Ro/SSA IgG subclass detected in SCLE and NLE sera in an ELISA using a synthetic Ro/SSA polypeptide. These studies show that the maternal anti-Ro/SSA autoantibodies in NLE-heart disease sera are predominantly IgG1 and are therefore likely to be present in the fetus at the time of gestation, when heart block usually develops. Second, differences in the clinical presentations of NLE (in utero vs. postnatal disease) cannot be attributed to differences in anti-Ro/SSA IgG subclasses. Finally, the subclass bound in the skin in SCLE is IgG1, a subclass capable of mediating tissue injury via complement or cellular effectors. PMID- 2250108 TI - Autoradiographic evaluation of monoclonal antibodies' access to melanoma associated antigens in melanoma xenografts. AB - Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect. PMID- 2250109 TI - The measurement of skin lymph flow by isotope clearance--reliability, reproducibility, injection dynamics, and the effect of massage. AB - The measurement of skin lymph flow was investigated using an isotope clearance technique (ICT). Multiple lymph flow determinations were undertaken in the skin of anaesthetized large white pigs to test for reproducibility, ascertain the most suitable tracer, study the influence of injection dynamics, and observe the effect of massage as a stimulus to lymph flow. Blood clearance of tracer was also investigated. Results demonstrated that lymphatic clearance is a monoexponential function with good reproducibility under controlled laboratory conditions. 99mTc colloid (TCK17 Cis) compared favorably with 131I-human serum albumin as a tracer and both performed better than colloid gold (198Au). Lymph flow was significantly faster in one pig than in the other. No difference existed between left and right sides or between caudal and rostral sites on each flank, but clearance was significantly slower in thigh than flank skin. Sub-epidermal injections cleared faster and more consistently than either deep or subcutaneous injections. Neither injection volume nor needle tract backflow of tracer influenced results, but local massage significantly enhanced clearance. Escape of 99mTc-colloid by the blood was negligible. These results indicate that skin lymph flow can be reliably measured when conditions are controlled. Extrinsic factors such as massage strongly influence lymph flow. Greater sensitivity in detecting degrees of lymphatic insufficiency may be achieved if a standardized stimulus to lymph flow is administered during isotope clearance measurement. PMID- 2250110 TI - Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil. AB - Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth. PMID- 2250111 TI - Interleukin-1 does not stimulate DNA synthesis of cultured human keratinocytes growth-arrested in growth-factor-depleted medium. AB - Interleukin-1, a multifunctional cytokine, plays a central role in inflammatory processes. Several reports have appeared demonstrating that IL-1 stimulates growth of keratinocytes under certain experimental conditions, and we have shown previously that it can act as a strong stimulator of DNA synthesis in murine keratinocytes that have been growth-arrested by removal of growth factors (GF) from the medium for several days. Using the same assay system, we report here that, in contrast to cultured mouse keratinocytes, growth-arrested adult and newborn human keratinocytes do not respond to IL-1 with an increase in DNA synthesis. The experiments were performed with primary and secondary cells and cells propagated with and without feeder layer prior to the assay. A growth response to IL-1 in the absence of exogenous GF was only observed in non-growth arrested human keratinocytes, i.e., when the cytokine was added for 24 to 48 h immediately after removal of other GF from the culture. Because keratinocytes continue to grow during this time anyway, although at a reduced rate, the additional growth observed with IL-1 could be explained as an enhancement of the growth-promoting effect by factors not previously completely removed from the culture. We would like to conclude from our results that, contrary to the findings in cultured mouse keratinocytes, IL-1 has no direct mitogenic effect on cultured human keratinocytes, but can still act as a growth promoter under certain conditions, apparently in concert with other GF. PMID- 2250112 TI - Human dermal fibroblasts modulate the effects of retinoids on epidermal growth. AB - We report the pharmacologic effects of retinoids in a human skin-equivalent model. This sophisticated culture system is composed, as in vivo, of a dermis and epidermis, and provides a unique in vitro system for studying dermal-epidermal interactions and thus, whether normal dermal fibroblasts influence the effects of retinoids on epidermal growth. Epidermalization was initiated on collagen substrates in which fibroblasts were either viable or lysed by osmotic shock. Retinoic acid, isotretinoin, and acitretin at 10(-6) M or 10(-7) M were added to the cultures just after epidermalization, then every two days. Epidermal growth was determined after 2 weeks in terms of the surface area, DNA content, and tritiated thymidine incorporation during the last 24 h of culture. In the absence of viable fibroblasts, retinoic acid and isotretinoin increased epidermal growth, whereas etretin inhibited it. In contrast, in the presence of viable fibroblasts, retinoic acid and isotretinoin inhibited epidermal growth, whereas etretin had no effect. Thus, retinoic acid and isotretinoin had a similar effect on keratinocyte proliferation that contrasted with that of etretin. Taken as a whole, these results show that fibroblasts, present within a collagen substrate, can modulate the pharmacologic effects of retinoids on epidermal growth. PMID- 2250113 TI - International Consensus Meeting on Hyperthermia: Final report. PMID- 2250114 TI - Thermoradiotherapy of patients with locally advanced carcinoma of the rectum. AB - The effectiveness of local hyperthermia was investigated in 56 patients with locally advanced carcinoma of the rectum (T4N0M0). All received combined heat and radiation therapy as a pre-operative treatment. The control group consisted of 59 patients with the same stage of disease as those who were only irradiated. Both groups of patients underwent the same surgical procedure. The total tumour dose of ionizing radiation was 40 Gy in 10 fractions, three times a week. The tumour was heated four or five times to a maximum of 42-43 degrees C by electromagnetic waves with a frequency of 905 MHz before irradiation. Each heating session lasted 60 min. Patients were selected on the principle of randomization: 16.1% of patients (n = 9; n: actual number of patients) showed complete response and 53.6% (n = 30) showed significant regression of the primary tumour compared with 1.7% (n = 1) and 33.9% (n = 20) in the control group, respectively. The differences were significant (p less than 0.05). It was found that thermoradiotherapy allowed the 5-year survival rate of patients to increase up to 35.6% (n = 12) compared with 6.6% (n = 7) in the control group (p less than 0.05). PMID- 2250115 TI - Temperature distributions during clinical scanned, focused ultrasound hyperthermia treatments. AB - In this study a scanned focused ultrasound (SFUS) system was used to heat 66 tumours at various anatomical locations in 52 patients. A total of 160 treatments were given. On average, temperatures were measured in 14 or 15 locations in the scanned volume. The time-averaged temperatures over the 30 min treatment period in the best treatment of each tumour were 44.0 +/- 2.4 degrees C (mean +/- SD) and 39.6 +/- 1.5 degrees C at the location of the highest and lowest sensor, respectively. On average, 39% of the sensors were above 42.5 degrees C. When only the cases that were judged to be good candidates for the hyperthermia device were analysed, 64% of the sensors reached a temperature over 42.5 degrees C with the highest temperature achieved being 45.9 +/- 2.3 degrees C and the lowest 40.7 +/- 1.4 degrees C. Although the system tested has many technical limitations (for example, fixed frequency, beam geometry and power during the scan cycle), the results demonstrate that therapeutic temperatures can be achieved in many tumours. Significantly better temperatures are expected when all of the theoretical potential of scanned focused ultrasound systems has been used. PMID- 2250116 TI - Clinical experience with a multi-element ultrasonic hyperthermia system: analysis of treatment temperatures. AB - A summary of tumour temperature data obtained from 31 patients who underwent 147 hyperthermia treatments with the Sonotherm 1000 ultrasonic system is presented. The treatment goal was to achieve a minimum of 42.0 degrees C in tumour for 60 min duration with normal tissues remaining below 43.0 degrees C. In 83% of treatments at least one measured tumour temperature reached or exceeded 42.0 degrees C at some time during the treatment. Nineteen per cent of these treatments had a time- and spatial-averaged temperature (measured in tumour) greater than or equal to 42.0 degrees C. A variety of anatomical sites were treated and these were grouped into four categories: groin/trunk, axilla, breast/chest wall and head/neck. Measured temperatures in tumours located in the groin and trunk sites were significantly higher (22% greater than or equal to 42 degrees C) than other locations. The head and neck treatment temperatures were significantly lower (8% of measured points greater than or equal to 42 degrees C. PMID- 2250117 TI - Effect of hyperthermia on cisplatin (CDDP) disposition to isolated perfused skin. AB - Hyperthermia has previously been postulated to enhance tissue uptake of systemically administered chemotherapeutic drugs. Normothermic (36.2 degrees C) and hyperthermic (42.1 degrees C) isolated perfused porcine skin flaps (IPPSF) were infused with cisplatin (CDDP) to assess any influence of heat on drug disposition to skin. A three-compartment physiologically relevant model was employed to interpret kinetically the measured arterial and venous flux profiles. Additionally, non-parametric methods were applied to these data in an effort to confirm the propriety of the model. Results of both approaches suggest that heat does not increase tissue uptake of CDDP after infusion in isolated perfused skin, although it does increase the mobility of CDDP as evidenced by shorter transit times through the IPPSF. These findings are similar to those seen in skin in vivo, but do not predict the enhanced in vivo uptake seen with hyperthermia in more highly perfused tissues. PMID- 2250119 TI - The effects of fractionated hyperthermia on normal canine muscle blood flow. AB - This study investigates the changes in normal canine muscle blood flow occurring during three fractions of 43 degrees C (60 min) hyperthermia. Blood flow was measured during heating at 1-, 3-, and 5-day intervals with a laser Doppler flowmeter. For 1-day intervals, blood flow oscillated during the first treatment reaching peak values of approximately 39 ml/min per 100 g of tissue after 8 min and 47 ml/min per 100 g of tissue after 40 min. Heatings at 1-day intervals showed both peaks in perfusion to persist during subsequent treatments with higher blood flows during later heatings. Results of the 3-day fractionated heating demonstrated lower blood flows during the second and third heatings than those at 1-day intervals. The third treatment of the 3-day fractionations showed a disappearance of the first peak and only a small increase in perfusion at the second peak (50 ml/min per 100 g of tissue). Perfusion studies at 5-day intervals demonstrated two peaks at approximately 15 and 40 min. Compared with the first treatment at 5-day intervals, the second and third treatments demonstrated decreased and increased peak perfusion values, respectively. This study suggests that the kinetics of blood flow changes during hyperthermia may be the result of several different mechanisms. There appear to be three different peaks which can be quantified during heating. These peaks may change during subsequent heating independently from one another. Further work must be performed to examine the physiological mechanisms responsible for each peak. PMID- 2250118 TI - Reversal of thermochemotherapeutic resistance to rhodamine 123 by verapamil. AB - Rhodamine 123 (R123) cytotoxicity and intracellular accumulation were studied at elevated temperature in R123-sensitive and R123-resistant B16 mouse melanoma cell lines. Hyperthermic potentiation of R123 cytotoxicity, present in the parental R123-sensitive cell line, was not present in the R123-resistant cell line. R123 resistant melanoma cells did not develop concomitant resistance to hyperthermia. Hyperthermic potentiation of R123 cytotoxicity was restored in the resistant cells by co-treatment with verapamil. Restoration of hyperthermic potentiation of R123 by verapamil in R123-resistant cells was accompanied by increased intracellular accumulation and decreased efflux of R123. These results suggest that verapamil may be used to re-establish thermal enhancement of drug cytotoxicity when thermochemotherapeutic resistance is present. PMID- 2250121 TI - Positioning of temperature measurement points using multiplanar computed tomography. AB - A method is described for the use of computed tomography and multiplanar reconstruction to depict in single images the full course of obliquely running thermometry catheters. In 14 patients given thermoradiotherapy for locally advanced breast carcinoma, reformatted images of the full catheter course were obtained for all 98 catheters so far tested. The main clinical advantage of this time-consuming procedure was the ability to determine the localization within the catheters of individual temperature measurement points of multipoint thermistor probes. It was also possible to study the localization of the measurement points in relation to the tumour margins. PMID- 2250120 TI - The effect of in vivo GSH depletion on thermosensitivity, radiosensitivity and thermal radiosensitization. AB - The effect of glutathione (GSH) depletion on the interaction of hyperthermia (HT) and single-dose external-beam radiation delivered at conventional dose rates (RT) and low-dose-rate brachytherapy (BT) was examined in a murine mammary adenocarcinoma (MTG-B). Tumour volume growth delay from the day of treatment to double the treatment volume (GDDV) was used as the experimental end-point. The growth delay for radiation alone was greater when combined with GSH depletion, while this level of GSH depletion produced no effect on the BT alone or HT alone response. The synergism ratio (SR) was calculated for all HT and RT or HT and BT protocols at each dose. Although depletion did not increase the SR for external beam treatments, the SR for HT and BT treatments was increased with GSH depletion. PMID- 2250122 TI - Concerning automation and standardization of treatment records. PMID- 2250123 TI - Development of decision support systems. AB - Use of hospital information systems (HIS) are no longer limited to administrative functions. The addition to these systems of decision support capability is now a necessity. Development of the decision support modules requires a different software architecture than that employed by most HIS systems today. This paper describes the generic uses of decision support throughout the many hospital applications. Several levels of decision support are outlined with examples to illustrate the many areas where decision support is useful. At LDS Hospital in Salt Lake City, Utah we have developed an HIS using a new software architecture which supports the creation of decision support applications. This system uses a frame structure to represent knowledge. Examples of the frames and their syntax is presented. Using the frame tools which are provided, an application developer can easily develop and test decision support modules which interact directly with the clinical user and the patient database. PMID- 2250124 TI - A unified approach to providing general anaesthesia monitoring with special reference to developing countries. AB - Information concerning general anaesthesia, monitoring and ergonomics has been assembled to present a plan for the introduction of necessary monitors into a department of anaesthesia. This includes reference to: (i) The need for instrumental monitors; (ii) Division of tasks between anaesthetist and monitor; (iii) User education; (iv) Anaesthetist/monitor interface; (v) Hospital infrastructure. Emphasis is placed on the continued need for anaesthetists to employ their own senses for monitoring in the traditional manner and the essential role instrumental monitors should play in helping trainees to refine and calibrate their clinical skills. It is suggested that in situations where neither mechanical ventilators are available nor instrumental monitors necessary to refine the conduct of general anaesthesia a transitional stage in evolution could be the presence of two persons with clearly defined responsibilities for all the anaesthesia tasks necessary during a safely conducted case. PMID- 2250125 TI - Comparison of acceptance and performance of automated and manual data management systems in intensive care. AB - A computerized data management system for intensive care was compared to conventional manual record keeping. The criteria for the comparison were the nurses' acceptance, the reliability in recording haemodynamic trends and the ability of the physicians' to recall patient data after being on duty for 24 hours. At the time of the study the data management system had been in routine clinical use for 18 months. During the study the data management system was replaced by manual record keeping for three weeks. The majority of the nurses preferred the data management system to the manual record keeping. It was also more reliable in collecting data for trend graphs from the patient monitors. The physicians made significantly less mistakes in recalling patient data when the data management system was in use than during manual record keeping. According to the criteria of the study, the data management system was superior to the conventional manual system. PMID- 2250126 TI - Whole body impedance measurements reflect total body water changes. A study in hemodialysis patients. AB - Fluid volume changes during hemodialysis was monitored by continuous whole body impedance measurements. The fluid changes recorded using this method was compared to fluid volume changes measured in plasma water (PV) using 125I-albumin, and extracellular volume (ECV) using 51Cr-EDTA before and after treatment, and total body water (TBW) changes reflected by continuous bed scale monitoring. Changes in impedance correlated to TBW changes, r = 0.80, p less than 0.001, while correlations to changes in ECV and PV were: r = 0.57 and r = 0.55, respectively, p less than 0.05. Alterations in body fluid volumes recorded with whole body impedance is best correlated to total body water changes. The use of continuous whole body impedance monitoring has been shown to offer a simple non-invasive method for recording total body water changes during hemodialysis. PMID- 2250127 TI - GUUS an expert system in the intensive care unit. AB - In cooperation with the Rotterdam School of Management of the Erasmus University in Rotterdam, an expert system GUUS was developed in the intensive care unit of the Department of Thoracic Surgery of the Leiden University Hospital. This expert system is able to diagnose postoperative haemodynamic problems in patients after coronary artery surgery and can give suggestions for therapy. GUUS has been developed by using the expert system shell Acquaint. The knowledge base was initially based on existing protocols and interviews with the medical head of the intensive care unit. The first prototype was tested and modified by using actual patient cases collected via special questionnaires. Subsequently the performance of GUUS was tested in a single blind comparison with three human experts. The results of this test were encouraging and initiated further development and implementation of the system. PMID- 2250128 TI - Clinical evaluation of computer-based respiratory care algorithms. AB - A collection of computer-based respiratory care algorithms were implemented as a prototype computer-based patient advice system (COMPAS) within the existing HELP hospital information system. Detailed medical logic recommended ventilator adjustments for 5 different modes of ventilation: assist/control (A/C), intermittent mandatory ventilation (IMV), continuous positive airway pressure (CPAP), pressure controlled inverted ratio ventilation (PC-IRV), and extracorporeal carbon dioxide removal (ECCO2R). Suggestions for adjusting the mode of ventilation, fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), peak inspiratory pressure, and several other therapeutic measures related to the treatment of severe arterial hypoxemia in adult respiratory distress syndrome (ARDS) patients were automatically presented to the clinical staff via bedside computer terminals. COMPAS was clinically evaluated for 624 hours of patient care on the first 5 ARDS patients in a randomized clinical trial. The clinical staff carried out 84% (320/379) of the computerized therapy suggestions. In response to a questionnaire distributed to clinical users of the system, 86% judged the system to be potentially valuable. Through implementation of COMPAS, a computer-based ventilatory therapy advice system, we have laid the groundwork for standardization of ventilator management of arterial hypoxemia in critically ill ARDS patients. PMID- 2250129 TI - Evaluation of a computerised system for medical records in an accident and emergency department. AB - This paper deals with the impact of the installation of a computerised record and data handling system in an urban Accident and Emergency department. This system became fully operational on the 14th of August, 1989 and replaced the previous manual method of administration. The new system allows 'real time' handling of patient details and generation of letters to both specialists and general practitioners. Audit of the department workload and data generation for research are improved. The current situation is described as well as potential benefits and constraints of the system. PMID- 2250130 TI - The general education initiative. Response to Carnine and Kameenui. PMID- 2250131 TI - Pull-out programs. PMID- 2250132 TI - Response to Hammill. PMID- 2250133 TI - Hypertext computer study guides and the social studies achievement of students with learning disabilities, remedial students, and regular education students. AB - Hypertext is a relatively new term for today's teachers, who work hard to stay abreast of the quickly changing field of computer technology in education. Hypertext as an educational tool is very different from traditional computer assisted instructional software, offering the reader immediate access through its computer format to supplemental information. Two related studies were conducted to design and field-test hypertext computer study guides. In Study 1, 40 students (10 with learning disabilities, 15 remedial, and 15 regular education) worked in three different treatment groups (lecture, lecture/computer study guide, and computer study guide). Study 2 involved the five lowest achieving students (two with learning disabilities and three remedial) from Study 1 in an A-B-A design. Results indicated that (a) the computer study guide treatment was as effective as lecture, (b) the lecture/computer study guide treatment was as effective as lecture, (c) posttest scores were higher for the computer study guide group, and (d) retention test scores were higher for the computer study guide group. PMID- 2250134 TI - Intrinsic motivation and school misbehavior: some intervention implications. AB - The intrinsic motivational concepts of self-determination, competence, and relatedness to others are highlighted to underscore their value in identifying motivational underpinnings for deviant and devious behavior. These constructs are woven into a working schema to differentiate intentional misbehavior in terms of whether it is reactive or proactive. Finally, from the perspective of such motivational thinking, implications for formal intervention research and experimental practice are illustrated. PMID- 2250135 TI - Learning disabilities in alcohol-dependent adults: a preliminary study. AB - To determine if neuropsychological deficits, known to precede alcohol use in those genetically predisposed to alcoholism, were present in an alcoholic population, 25 male alcoholics (mean age 41.1) were interviewed concerning alcohol usage, educational difficulties in elementary school, and family history of alcoholism. Using a regression table, discrepancies between current IQ on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Wechsler, 1981) and achievement on the Woodcock-Johnson Psycho-Educational Battery (WJB) (Woodcock & Johnson, 1977) were calculated to determine present learning status. Forty percent of the alcoholics were found to have had special education, remedial services, or repeated grade failure concurrent with a familial history of alcoholism and current discrepancies indicative of learning disability. There were no significant differences on intelligence, years of drinking, or mean grades completed in school between this group and the rest of the subjects who did not receive services in school. Conclusions were that childhood learning disorders may be related to the development of alcoholism, particularly when alcoholism is in the family, and that special educators have a role to play in the prevention and treatment of alcoholism. PMID- 2250136 TI - Referencing: the cohesive use of pronouns in the written narrative of college underprepared writers, nondisabled writers, and writers with learning disabilities. AB - The purpose of this study was to explore whether college normally achieving writers (n = 35), writers with learning disabilities (n = 35), and underprepared writers (n = 35) demonstrated any differences in their ability to utilize the semantic roles and syntactic rules needed to apply cohesive referencing in written text. Cohesive referencing (the ability to assign roles to the speaker and addressee in written communication) is a critical aspect of written language. In addition, the study explored the relation between referential cohesion and the quality and coherence of a written text. PMID- 2250137 TI - Training phonemic segmentation ability with a phonemic discrimination intervention in second- and third-grade children with reading disabilities. AB - The present study examined the possibility that phonemic discrimination training could improve the phonemic segmentation ability of children with reading disabilities. Half of the 32 children with reading disabilities (14 male and 4 female second graders and 10 male and 4 female third graders, with mean ages of 99.2 and 109.7 months, respectively) deficient in phonemic segmentation skills were assigned to the training group, while the other half acted as a nontrained control group. The trained children were successful at significantly improving their performance on the phonemic segmentation task. The control group made no improvement. Requiring children with reading disabilities to make discriminations concerning phonemic information may have helped them discover properties of the phoneme that they previously did not know. PMID- 2250138 TI - Persisting problems of adults with learning disabilities: self-reported comparisons from their school-age and adult years. AB - The issue of persistence of learning disabilities into the adult years was investigated. The study examined the self-reported comparisons of problems resulting from learning disabilities during school-age years (retrospectively) and in adult years. The responses of 133 adults categorized as highly successful and moderately successful in employment showed that both groups deteriorated markedly in the areas of functioning typically included in diagnostic and remediation efforts. This established a case for persistence and highlights an important issue for those who are directly or indirectly concerned about adults with learning disabilities. PMID- 2250139 TI - Teacher competency testing: what teachers of students with LD need to know. AB - In 1964, North Carolina became the first state to enact a testing program for initial certification of teachers. Today, almost all states and the District of Columbia are actively planning or implementing teacher testing programs; six are administering tests in the specific area of learning disabilities. The objectives and content areas of knowledge included in competency testing programs within this specialized area of teacher competence were analyzed, and comparisons were completed across knowledge areas and among states. In general, much similarity exists in what teachers of students with learning disabilities in different states are expected to know. This information represents a strong foundation for planning, implementing, and evaluating training programs for all teachers. PMID- 2250140 TI - The effects of blending and spelling training on the decoding skills of young poor readers. AB - Blending and spelling training were compared in this experiment to determine which intervention would improve the decoding skills of two first-grade boys with learning disabilities who were in the phonetic cue stage of reading. Additionally, the two boys received pre- and posttest administrations of a phonemic segmentation task. Although neither intervention proved superior, the children met the learning criterion for both interventions and demonstrated both maintenance and generalization of their skills. They also improved their phonemic skills, even though independent training in this area was not provided. It appeared that the equivalence of the interventions may have been due to the intensive instructional setting and use of systematic error analysis procedures. PMID- 2250141 TI - A nonlinear structured population model of tumor growth with quiescence. AB - A nonlinear structured cell population model of tumor growth is considered. The model distinguishes between two types of cells within the tumor: proliferating and quiescent. Within each class the behavior of individual cells depends on cell size, whereas the probabilities of becoming quiescent and returning to the proliferative cycle are in addition controlled by total tumor size. The asymptotic behavior of solutions of the full nonlinear model, as well as some linear special cases, is investigated using spectral theory of positive simigroup of operators. PMID- 2250142 TI - Computer-aided three-dimensional images of the helical structure in the apical tubule of absorbing epithelia. AB - Computer-aided three-dimensional models of the helical structure within an apical tubule (AT) of several absorbing epithelia (kidney proximal tubule, visceral yolk sac, and ductuli efferentes) were constructed using ray-tracing graphics software to further understand the highly ordered structural configuration. Our previous electron microscopic studies using thin-section technique have first revealed the helical structure within the AT fixed in situ with a mixture of formaldehyde, glutaraldehyde, and osmium tetroxide. In the present study, we construct a computer-aided three-dimensional model of the helical structure in the AT to explain quantitative data obtained by the electron microscopy. The model could well explain several aspects of electron microscopical images and enables us to understand more clearly the three-dimensional configuration of the unique structure associated with the AT. PMID- 2250143 TI - 125I-endothelin binds to fibroblasts beneath the epithelium of rat small intestine. AB - Rats were intravenously injected with synthetic 125I-endothelin, and then were fixed by intracardiac perfusion at 10 min, 30 min and 1 hr after the injection. Localization of 125I-endothelin was examined in the small intestine by light and electron microscopic radioautography. Through the time course examined, more than seventy percent of total silver grains were localized in the fibroblasts, especially beneath the basal lamina of epithelium of the intestinal villi. Silver grains were observed mostly on the thin processes, and also on the vacuoles. At 10 min, 80% of silver grains on the fibroblasts were located on the plasmalemma. By the chase, grains on the plasmalemma decreased, and silver grains in the cytoplasm increased gradually. PMID- 2250144 TI - Substrate interactions in the development of insulin resistance in type II diabetes and obesity. PMID- 2250145 TI - Involvement of dopamine D1 receptors in the control of growth hormone secretion in the rat. AB - The effects of dopamine on GH release were investigated both in vivo in freely moving intact rats and in rats with a mediobasal hypothalamic lesion, and in vitro in a perifusion system using dispersed male rat pituitary cells kept in primary culture. In vivo, dopamine (5 mg/kg body weight) induced a rapid and very transient increase in plasma GH levels in lesioned but not in intact rats. This increase was markedly inhibited by a prior injection of the D1 antagonist SCH 23390 (0.5 mg/kg) but not of the D2 antagonist domperidone (0.5 mg/kg). The D1 agonist SKF 38393 induced a dose-dependent stimulation of GH release in lesioned rats, and the effect obtained with a dose of 5 mg/kg was abolished by pretreatment with SCH 23390 (0.5 mg/kg). In vitro, dopamine (0.1 mumol/l) and SKF 38393 (0.1 mumol/l) provoked a rapid and reversible release of GH from superfused rat pituitary cells; this effect was markedly inhibited by simultaneous superfusion of SCH 23390 (1 mumol/l). These findings indicate that dopamine can stimulate basal GH release at the pituitary level and that this stimulation is mediated by D1 but not by D2 receptors. They also support the hypothesis that unidentified hypothalamic neurohormones may modulate this effect. PMID- 2250146 TI - Control of ion transport in the thyroid: prostaglandin E2 activates cation transport on the basal membrane of cultured porcine thyroid cell monolayers. AB - Confluent monolayers of cultured porcine thyroid cells transport fluid from the apical to the basal surface, forming circumscribed zones of detachment (domes) from the culture dish substrate. Stimulation of fluid transport by prostaglandin E2 (PGE2; 1 mumol/l) was associated with an increase in transepithelial potential (TEP). Intracellular potentials (equal to the potential difference across the apical membrane of the cell, Eapical) and the TEP were measured in individual domes so that the potential difference across the basal membrane of the cell (Ebasal) could be calculated from the relationship TEP = Eapical-Ebasal. The PGE2 induced increase in TEP was associated with hyperpolarization of the basal membrane, accompanied by a slight depolarization of the apical membrane. Lines of best fit by least-squares regression showed Eapical = -20.3 mV +0.219 TEP (correlation coefficient r = 0.627; P less than 0.001) and Ebasal = -20.3 mV 0.781 TEP (r = 0.944; P less than 0.001). Phenamil (1 mumol/l), a Na+ channel selective amiloride analogue, reduced the TEP from 13.25 +/- 0.58 (S.E.M.; n = 56) to 2.39 +/- 0.16 mV (n = 51; P less than 0.001) and hyperpolarized the apical membrane potential from -20.7 +/- 0.68 (n = 60) to -32.2 +/- 0.83 mV (n = 105; P less than 0.001). The response of the TEP to phenamil was immediate, and was promptly reversed on washing; in contrast, addition of 5-(N-ethyl-N isopropyl)amiloride (20 mumol/l; selective for Na+/H+ antiporters) resulted in a slow depolarization over 30 min with a slow recovery after washout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250147 TI - Analysis of the ratio of biological to immunological LH secreted during the oestrogen-induced LH surge in the ewe. AB - Plasma concentrations of in-vitro biological and immunological LH were measured throughout the LH surge in cyclic ewes and in ovariectomized ewes treated i.m. with oestradiol benzoate. Both activities increased in parallel during the LH surge in both groups, although the ratio of biological to immunological activities (B/I ratio) was highest at the peak of the LH surge. The two activities were highly correlated (r = 0.86-0.92), with similar slopes from their regression analysis for the cyclic and ovariectomized groups (1.15 and 1.16 respectively). However, the intercepts of the regression lines did not pass through the origin, but intersected the y (radioimmunoassay) axis, suggesting that these serum samples contained immunoactivity not associated with LH bioactivity. In conclusion, an increase in the LH B/I ratio was observed during the LH surge in oestrogen-treated ovariectomized ewes and in cyclic ewes. This increase was not attributable to a change in the relationship between these two LH activities during the LH surge, but rather to the detection of bioinactive immunoactive material in plasma of unknown composition. PMID- 2250148 TI - Effects of modifying gonadotrophin-releasing hormone input before and after the oestrogen-induced LH surge in ovariectomized ewes with hypothalamo-pituitary disconnection. AB - The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 micrograms oestradiol benzoate (OB). The ewes were given a bolus pulse of 2.25 micrograms GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P less than 0.05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P less than 0.05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. In experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 micrograms/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P less than 0.05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen. PMID- 2250149 TI - Effects of altered dietary sodium intake on hormonal profiles in salt-sensitive hypertensive rats. AB - Blood pressure and selected putatively influential hormones were measured in Brattleboro rats which were without diabetes insipidus and which were subjected to various manipulations in dietary sodium intake. Rats fed a control diet from weaning to 16 weeks of age showed a slow increase in blood pressure whereas rats fed a sodium-enriched diet for the same period exhibited sustained hypertension (115 +/- 3 versus 169 +/- 5 (S.E.M.) mmHg). In animals fed a sodium-enriched diet plasma concentrations of antidiuretic hormone (ADH) were significantly increased from 55 +/- 8 to 108 +/- 5 fmol/l. Rats fed the control diet from weaning (group A) and subsequently maintained on that diet or changed to a sodium-enriched diet or sodium-deficient diet showed no differences in their blood pressure. Plasma hormone concentrations were similar in these groups, with the exception of aldosterone suppression in rats switched from control to a sodium-enriched diet (0.26 +/- 0.04 versus 0.08 +/- 0.03 nmol/l; P less than 0.001). Animals fed the sodium-enriched diet from weaning to 16 weeks of age (group b) and either maintained on that diet or changed to a control diet showed little change in their established hypertension. Transfer to the control diet was associated with increased plasma renin concentrations (PRC) (13.8 +/- 2.1 to 122.6 +/- 6.2 nmol/l) and plasma aldosterone concentrations (0.04 +/- 0.01 to 0.08 +/- 0.01 nmol/l; P less than 0.001) but corticosteroids and ADH concentrations were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250150 TI - Synergism of testosterone propionate with growth hormone in promoting growth of hypophysectomized rats: effect of sexual differentiation. AB - The effect of testosterone propionate (TP), alone and in combination with porcine GH, on the growth of hypophysectomized rats was investigated. An initial study determined doses of TP and GH which would result in a synergistic response. Hypophysectomized male rats, approximately 40 days of age, received GH at doses of 5, 25 and 62.5 micrograms/day administered in two injections/day at 08.00 and 16.00 h. At all doses of GH, administration of TP at 100 micrograms/day significantly enhanced the GH-stimulated rate of growth. This growth enhancement by TP was greatest in combination with GH at 25 micrograms/day. In a subsequent study, growth responses to 25 micrograms GH/day and 100 micrograms TP/day were examined in animals with differing degrees of sexual differentiation. Sex groups were: intact males, males castrated at 11 days of age and females administered 100 micrograms TP at 3 days of age (masculinized rats), and males castrated at 2 days of age and normal females (non-masculinized rats). In all sex groups, growth of hypophysectomized rats was stimulated by GH. Genetic sex and masculinization did not influence the response to GH. Masculinized hypophysectomized rats exhibited significantly greater rates of growth and final live, empty body, liver and kidney weights than non-masculinized hypophysectomized rats. All sex groups other than normal females responded synergistically to the combination treatment of GH plus TP. Rats that experienced neonatal exposure to testosterone became programmed to respond to testosterone and demonstrated greater rates of growth and body and organ weights when administered the combination of GH plus TP. These data indicate that TP synergizes with GH to promote growth of hypophysectomized rats appropriately programmed to respond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250151 TI - Suckling-induced release of cholecystokinin into plasma in the lactating rat: effects of abdominal vagotomy and lesions of central pathways concerned with milk ejection. AB - Plasma levels of cholecystokinin were increased in response to suckling in lactating rats. Efferent electrical stimulation of the vagal nerve increased the concentration of cholecystokinin in plasma. Abdominal vagotomy was found to block the suckling-induced release of cholecystokinin. Furthermore, lesions to the lateral midbrain, which disrupt the oxytocin-mediated milk-ejection reflex, were shown to inhibit the increase in plasma cholecystokinin. These results show that the suckling-induced release of cholecystokinin into plasma in lactating rats is dependent upon the vagal nerves and the central neural structures concerned with milk let-down. PMID- 2250152 TI - Ovarian secretion rates and peripheral concentrations of inhibin in normal and androstenedione-immune ewes with an autotransplanted ovary. AB - Active immunization of sheep against androstenedione results in an increase in ovulation rate that is associated with increased plasma levels of LH and progesterone, but not FSH. Although immunized ewes have more activated follicles the secretion rate of oestradiol is not increased. An experiment was conducted to examine the effect of androstenedione immunity on the ovarian secretion and peripheral plasma concentrations of inhibin. Merino ewes in which the left ovary had been autotransplanted to a site in the neck were divided into control (n = 5) and androstenedione-immune (n = 6) groups. Ovarian and jugular venous blood was collected every 10 min at two stages of the follicular phase, 21-27 h and 38-42 h after a luteolytic dose of an analogue of prostaglandin F2 alpha (PG), and every 15 min for 6 h on day 10 of the subsequent luteal phase. The ewes were monitored regularly for luteal function by measurement of the concentration of progesterone and preovulatory LH surges. The concentration of inhibin in jugular and ovarian venous plasma was determined by radioimmunoassay and ovarian secretion rates and peripheral concentrations are expressed as pg of 1-26 peptide fragment of the alpha chain. The ovarian secretion rate of inhibin tended to be greater in androstenedione-immune ewes at all stages of the oestrous cycle measured, with this difference being statistically significant (P less than 0.05) during the luteal phase (100 +/- 40 and 260 +/- 80 (S.E.M.) pg/min for control and immune groups respectively). The pattern of ovarian inhibin secretion exhibited pulsatile-like fluctuations which were not associated with LH pulses. Peripheral concentrations of inhibin were generally higher in immunized than in control ewes with this difference being significant (P less than 0.01) from day 4 to 14 of the luteal phase (59 +/- 5 and 110 +/- 7 ng/l for control and immune respectively). The ovarian secretion rate of immunoactive inhibin was greater (P less than 0.01) during the follicular phase than during the luteal phase in both groups of ewes, and peripheral concentrations of inhibin increased (P less than 0.001) following injection of PG in ewes from both treatment groups. We concluded that androstenedione immunity results in an increase in ovarian inhibin secretion, an effect that can probably be attributed to the greater number of large oestrogenic follicles present in the ovaries of these ewes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2250153 TI - Cytoplasmic pH in the action of insulin-like growth factor-I in cultured porcine thyroid cells. AB - The effects of insulin-like growth factor-I (IGF-I) on cytoplasmic pH (pHi) and [3H]thymidine incorporation were studied in primary cultures of porcine thyroid cells. IGF-I alkalinized thyroid cells and stimulated thymidine incorporation in a dose-dependent manner; the effects of IGF-I on alkalinization (the maximal rates of change of cytoplasmic pHi/min ((dpHi/dt)max)) and thymidine incorporation were observed at 2 ng/ml and were maximal at 100 ng/ml, with half maximal stimulation at approximately 10 ng/ml. The results indicate that Na+/H+ exchange or cell alkalinization may function as a transmembrane signal transducer in the action of IGF-I on thyroid cell proliferation. Several mitogens and comitogens which activate sodium hydrogen exchange, including epidermal growth factor, platelet-derived growth factor and nerve growth factor, have been listed. Activation with IGF-I has not, however, been presented before. Thus the present study constitutes the first demonstration of IGF-I-stimulated activation of Na+/H+ exchange or cell alkalinization. PMID- 2250154 TI - Mitosis in the oesophageal epithelium of rats during chronic antithyroid treatment with carbimazole. AB - The mitotic activity of the oesophageal epithelium of male rats maintained under carefully controlled conditions was studied, using the metaphase-arrest agent, vincristine sulphate. The accumulation of metaphases was linear (r = 0.97). In untreated rats there was a clear mitotic rhythm with a peak metaphase index (expressed as a percentage) of 12.4 +/- 0.86 (S.E.M.) at 12.00-15.00 h and a trough of 1.3 +/- 0.35 at 24.00 h. The overall mean metaphase index was 5.4 +/- 0.76. The effect of treatment with the antithyroid agent, carbimazole (0.1 g/100 ml in the drinking water), for 3 weeks was to depress the higher values at 12.00 18.00 h (P less than 0.01), while leaving the overall index unchanged. Carbimazole caused a significant (P less than 0.01), transient 40% increase in the metaphase index after 2 days; thereafter the metaphase index remained at control levels until 12 weeks of treatment when a steady decline occurred until 24 weeks. The results are in contrast to those in previously described experiments on thyroid follicular cells which show a large increase in the first few days of treatment, followed by a steady decline towards control levels at 12 weeks. The metabolic activity of the animals is about 50% of normal at 12 weeks when both the oesophageal epithelium and the thyroid follicular cells begin to show a reduction in proliferative activity. PMID- 2250155 TI - Immunohistochemical localization of kallikrein within the prolactin-producing cells of the rat anterior pituitary gland. AB - The localization of tissue kallikrein in the pituitary gland of rats was investigated by an immunohistochemical technique using antiserum against rat urinary kallikrein. Kallikrein-positive cells were detected in the anterior lobe of the pituitary of both male and female rats, but were not observed in the posterior lobe of the pituitary in either sex. The kallikrein-positive cells in the anterior pituitary of female rats in oestrus were found to correspond to the prolactin-producing cells, whereas the cells producing GH, LH and ACTH were negative for kallikrein. It is possible, therefore, that the tissue kallikrein may be involved in the production of prolactin and not that of the other anterior pituitary hormones, such as GH, LH, FSH, ACTH and TSH. PMID- 2250156 TI - Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro. AB - Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5.6 mmol glucose/l. 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16.7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2.8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11.1 mmol/l. At 5.6 mmol glucose/l, GRP (100 pmol/1-100 nmol/l) increased (by 50-70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 mumol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores. PMID- 2250157 TI - Cytosolic glucocorticoid receptors in the porcine lung during development and after hypophysectomy or thyroidectomy. AB - The ontogeny of fetal lung glucocorticoid receptors and their regulation by the fetal pituitary, adrenal and thyroid gland during lung maturation were investigated. Sites with a specificity typical of glucocorticoid receptors were detectable in lung cytosol, with the order of potency of steroids being dexamethasone greater than cortisol greater than corticosterone greater than 11 deoxycorticosterone greater than progesterone greater than 17 alpha hydroxyprogesterone greater than oestradiol-17 beta congruent to testosterone congruent to androstenedione congruent to oestrone. The binding affinity for [3H]dexamethasone was high (Kd = 0.23-0.60 nmol/l) and showed an age-related decrease during the perinatal period when cortisol levels were high. After charcoal treatment of the cytosol, however, a decrease in binding affinity was not as clearly evident. The Kd decreased following hypophysectomy of fetuses; thyroidectomy had no significant effect. The concentration of glucocorticoid receptors was high from day 82 to day 100 of gestation (1437 fmol/mg protein) and declined progressively to a lower value at term and following birth (660 fmol/mg protein). Hypophysectomy, but not thyroidectomy, prevented the age-related decline in receptor concentration. Lung glycogen content declined with fetal ageing in association with increases in plasma concentrations of cortisol and thyroxine and with changes in Kd and Bmax, but appeared to be more closely associated with concentrations of thyroxine. Hypophysectomy of fetuses decreased concentrations of both cortisol and thyroxine and prevented the depletion of lung glycogen content. Preliminary results from thyroidectomized fetuses showed decreases in plasma thyroxine and lung glycogen content compared with day-82 fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250158 TI - Binding of 125I-labelled thyrotrophin to transfected human thyrocytes (SGHTL-34 cells). AB - The binding of 125I-labelled bovine TSH to a human thyroid cell line (SGHTL-34) has been studied. Binding to hormonally responsive cells was time dependent, specific and reversible. Scatchard analysis of the binding data indicated the presence of a single binding site with high affinity (intrinsic dissociation constant (Kd) = 0.25 +/- 0.08 nmol/l; mean +/- S.E.M.; n = 4) and low capacity (maximum binding (Bmax) = 104 +/- 29 fmol/mg protein; mean +/- S.E.M.; n = 4). Hill plots confirmed the presence of a single site. Kinetic data demonstrated close agreement between the Kd and Bmax obtained from the competition data (Kd = 0.23 +/- 0.35 nmol/l; Bmax = 161 +/- 83 fmol/mg protein; n = 6). PMID- 2250159 TI - Epidermal growth factor in small antral ovarian follicles of pregnant women. AB - Levels of epidermal growth factor (EGF) and steroids were measured by radioimmunoassay in follicular fluid (FF) aspirated from 114 small antral follicles with diameters from 1 to 6 mm and in serum from 19 women undergoing Caesarean section at term. Concentrations of EGF in FF were inversely and significantly correlated to follicular size, being 4.7 +/- 0.4 (mean +/- S.E.M.) nmol/l in follicles of 1-2 mm in diameter and declining to 2.2 +/- 0.2 and 1.4 +/ 0.2 nmol/l in follicles of 3-4 mm and 5-6 mm in diameter respectively. The mean +/- S.E.M. concentration of EGF in serum (0.7 +/- 0.03 nmol/l) was significantly lower than that in FF. Levels of EGF, progesterone and oestradiol in FF were not significantly correlated to one another. In contrast to EGF, levels of progesterone and oestradiol in FF did not vary significantly with follicular diameter in these small follicles. On the basis of these results we suggest that EGF is synthesized in small human antral follicles, and that EGF stimulates granulosa cell proliferation and follicle growth up to 6 mm in diameter. Furthermore, the high intrafollicular levels of EGF may protect the small follicles against untimely effects of high levels of FSH, for instance during the mid-cycle surge of gonadotrophins. It is concluded that EGF plays an important role as an autocrine and/or paracrine regulator of development of small antral follicles in women. PMID- 2250160 TI - Concurrent protein synthesis is required for in vivo chitin synthesis in postmolt blue crabs. AB - Chitin synthesis in crustaceans involves the deposition of a protein polysaccharide complex at the apical surface of epithelial cells which secrete the cuticle or exoskeleton. The present study involves an examination of in vivo incorporation of radiolabeled amino acids and amino sugars into the cuticle of postmolt blue crabs, Callinectes sapidus. Rates of incorporation of both 3H leucine and 3H threonine were linear with respect to time of incubation. Incorporation of 3H threonine into the endocuticle was inhibited greater than 90% in the presence of the protein synthesis inhibitor, puromycin. Linear incorporation of 14C glucosamine into the cuticle was also demonstrated; a significant improvement of radiolabeling was achieved by using 14C-N acetylglucosamine as the labeled precursor. Incorporation of 3H-N acetylglucosamine into the cuticle of postmolt blue crabs was inhibited 89% by puromycin, indicating that concurrent protein synthesis is required for the deposition of chitin in the blue crab. Autoradiographic analysis of control vs. puromycin-treated crabs indicates that puromycin totally blocks labeling of the new endocuticle with 3H glucosamine. These results are consistent with the notion that crustacean chitin is synthesized as a protein-polysaccharide complex. Analysis of the postmolt and intermolt blue crab cuticle indicates that the exoskeleton contains about 60% protein and 40% chitin. The predominant amino acids are arginine, glutamic acid, alanine, aspartic acid, and threonine. PMID- 2250161 TI - Behavior of rabbit dental tissues in heterospecific association with embryonic quail ectoderm. AB - The behavior of dental tissues from the rabbit, Oryctolagus cuniculus, in association with epithelium from the quail, Coturnix coturnix japonica, has been examined. Adult and embryo rabbits were employed in this study. Dental papillae from teeth at the cap stage from rabbit embryos and dental pulp from adult rabbits were isolated surgically and recombined with skin ectoderm from 72-hour old quail embryos. The recombined tissues were cultured for 48 hours on semi solid medium and subsequently removed and placed on chorio-allantoic membranes of 7-day-old chick embryos. Control cultures (dental pulp, dental papillae, and quail ectoderm) showed regression, atrophy, or differentiation according to the phenotype of the tissue. After 8 days in explant culture, heterologous recombinants composed of dental papillae and flank skin ectoderm from quail embryos developed differentiated chimeric tooth structures. It was unclear whether or not enamel was being secreted. The fact that the interactions between the enamel epithelium and the dental papillae are reciprocal is well known. The differentiation of odontoblasts can only occur in the presence of an enamel organ. Thus, the quail epithelium must have been induced to become an enamel organ, the lack of enamel proteins notwithstanding. Apical pulp and root pulp from adult rabbits plus quail ectoderm showed a high degree of regression and atrophy. At around 15 days of gestation, the rabbit dental papillae at the cap stage have already acquired odontogenic potential. By contrast, under the same experimental conditions, the dental pulp from continuous-growth teeth from adult rabbits did not show odontogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250162 TI - Either chick embryo dermis or retinoid-treated mouse dermis can initiate glandular morphogenesis from mammalian epidermal tissue. AB - Excess retinoids can cause developing mouse vibrissa follicles to be transformed into mucous glands in organ culture. The objective was to test the hypothesis that retinoids act in this system by altering morphogenetic properties of the dermis. After inititation by retinoic acid (RA) in organ culture, glands were shown to develop further in embryonic skin grafted to the chick chorioallantoic membrane (CAM). Recombinants of 12.5 day mouse epidermis with untreated or RA treated mouse or chick dermis were then grafted to CAM for 7 days. For homospecific recombinants, 13.5 day mouse dermis originated from 11.5 day skin cultured for 2 days, with or without 5.2 microgram/ml RA. For heterospecific recombinants, 12 day dermis came from chick embryos, previously injected with 250 microgram RA. Glands were absent from the homospecific recombinants including untreated mouse dermis, but appeared in 26% of those with RA-treated dermis. Among heterospecific recombinants, 75% of those with RA-treated chick dermis and 29% of those with untreated dermis had glands. Untreated 10-12 day chick skin contained two forms of endogenous vitamin A, retinol (4.5 microgram/g protein) and dehydroretinol (3.7 microgram/g protein), while 13-14 day mouse skin contained only retinol (1.8 microgram/g protein), as shown by high performance liquid chromatography. RA injection increased retinol and dehydroretinol in chick skin, while RA was undetectable. Thus RA can act through mouse dermis to form epithelial glands and through chick dermis to increase the incidence of glands. The glands in recombinants with untreated chick dermis may result from the higher levels of endogenous retinoids in chick skin, compared with mouse skin. PMID- 2250163 TI - Radioreceptor assay for growth hormone in coho salmon (Oncorhynchus kisutch) and its application to the study of stunting. AB - Binding sites for native chum salmon growth hormone (sGH) in coho salmon (Oncorhynchus kisutch) hepatic membranes were analyzed by radioreceptor assay. Displaceable (specific) binding represented up to 25% of total radiolabeled sGH added. Binding was dependent on buffer pH and membrane protein concentration, and was complete by 24 hours at 15 degrees C. Specific binding was greatest in liver membranes, and was also detected in muscle, ovary, gill, kidney, and brain. Scatchard analyses indicated a single class of hepatic binding sites that were specific for sGH. In stunts, abnormal seawater salmon with elevated plasma GH levels and inhibited growth, specific binding of sGH to liver membranes was three times lower than in normal seawater smolts. The concentration of salmon GH binding sites was decreased in stunt livers by 60%, while their affinity for sGH was unchanged. Down-regulation of hepatic GH receptors by high plasma GH levels may explain in part the low sGH binding in stunts. PMID- 2250164 TI - Action of 1,25-dihydroxyvitamin D3 and parathyroid hormone on 45calcium uptake by the yolk sac membrane of chick embryos. AB - During development, the chick embryo mobilizes the calcium it needs from two extraembryonic sources, initially from the yolk and later from the eggshell. Calcium may be hormonally regulated during avian embryogenesis, but details of this regulation are lacking. We investigated the effects of 1,25 dihydroxycholecalciferol [1,25(OH)2D3], bovine parathyroid hormone [bPTH], and vehicle [ethanol or saline] on blood calcium values and incorporation of 45Ca into the yolk sac membrane of 9, 12, and 15 day chick embryos. Control data were also collected from uninjected 6 day embryos. Solutions were injected directly into the yolk sac compartment 48 and 24 hours prior to the experiment. Exogenous 1,25(OH)2D3 induced hypercalcemia in all age groups examined, while exogenous PTH induced hypercalcemia in day 12 and 15 embryos. Small disks of yolk sac membrane were incubated in medium to which 45Ca was added and assayed for 45Ca content at various intervals after start of incubation. In control yolk sac tissue, the uptake of 45Ca was greatest in younger embryos with decreasing uptake at developmentally more advanced ages; 1,25(OH)2D3 treatment significantly enhanced the uptake of 45Ca into yolk sac tissue in all groups (9, 12, and 15 day embryos). PTH treatment caused a significant elevation in 45Ca uptake in the day 12 and 15 embryos. PMID- 2250165 TI - Studies on the decondensation of human, mouse, and bull sperm nuclei by heparin and other polyanions. AB - We report heparin-induced decondensation of human, mouse, and bull sperm nuclei. Decondensation did not occur if the spermatozoa were intact but only if the membranes were severely damaged by freezing and thawing or by treatment with a detergent. If a disulphide bond reducing agent (thiol) was absent, decondensation of human sperm nuclei was usually a relatively slow process, with large interindividual variation. Mouse and bull sperm nuclei did not decondense in the absence of a thiol. With a thiol relatively low concentrations of heparin induced a rapid decondensation of the sperm nuclei of all three species. The decondensation activity was not specific for heparin; other polyanions were also active, with heparin being the most effective compound. It is supposed that heparin and other polyanions induce sperm nuclear decondensation because they deplete protamines from the chromatin. Thus the negatively charged phosphate groups of the DNA are no longer opposed by positively charged protamines. Consequently the mutual repulsion of unopposed phosphate groups causes the DNA molecules to stretch, which results in an increase of the sperm nuclear volume. Since heparin and other polyanions induce decondensation under physiological pH and temperature, polyanions might also be active in the oocyte. PMID- 2250166 TI - Sex-determining potencies vary among female incubation temperatures in a turtle. AB - Reptiles whose sex is determined by incubation temperature typically exhibit all male or all-female sex ratios over a wide range of incubation temperatures. The question arises as to whether the various all-female temperatures (or the various all-male temperatures) are equivalent in their "potency", or capacity to effect female determination. In map turtles, warm incubation temperatures produce all females and cool ones produce all males. We compared sex determining potencies of two all-female temperatures, 31 degrees C and 32.5 degrees C, by incubating eggs first at a male-producing temperature (26 degrees C) and then shifting them to the warm temperatures. The resulting sex ratio was significantly more male biased in the 26 degrees C----31 degrees C shift than in the 26 degrees C----32.5 degrees C shift, indicating that 32.5 degrees C has the greater female potency. These results point to the possibility that sex determination depends on a quantitative rather than qualitative level of gene expression. PMID- 2250167 TI - Expression of the Axd (axial defects) mutation in the mouse is insensitive to retinoic acid at low dose. AB - The Axd mutation in the mouse acts by an unknown mechanism to cause lumbosacral open neural tube defects and a variety of tail anomalies. Retinoic acid (RA) plays a number of different physiological and developmental roles and has been shown to affect neurulation in mice and other species. Indeed, reports have shown that this biologically active compound (or its metabolites) at low dose can alter the incidence of neural tube defects (NTD) in curly-tail (ct), splotch (Sp), and delayed splotch (Spd) mice, strains that are genetically predisposed to such abnormalities. The aim of the present study was to determine if RA administered under similar conditions would affect the penetrance or expression of the Axd mutation or survival of Axd homozygotes. Axd/+ and +/+ dams were exposed to RA intraperitoneally (5 mg/kg) on D9 postcoitus. No difference in incidence or extent of neural tube defects or other axial anomalies was detected among embryos of Axd/+ dams given RA compared with those administered vehicle only. This finding is consistent with the diversity of gene-controlled steps required for neurulation and the differing sensitivities of specific mutants to rescue by extrinsic agents. PMID- 2250168 TI - Cerebral rhinocele, hydrocephalus, and cleft lip and palate in infants with cardiac fibroma. AB - Cardiac transplantation was performed in two infants with unresectable fibromas of the myocardium. In one patient, lip surgery was also required for unilateral cleft lip and palate. At autopsy, communicating hydrocephalus of mild to moderate degree was found in both cases. In the patient with facial clefts, there was also a large, ipsilateral cyst, or rhinocele, of the olfactory lobe. This unusual lesion, which seems to represent a previously unreported malformation, was apparently formed by segmental dilatation of a persistent olfactory ventricle. Cerebral or cranial anomalies are thought to be rare in cases of cardiac fibroma; however, macrocephaly was present in five patients. Furthermore, presenting abnormalities among previously reported cases included hydrocephalus in one case, and cleft lip and palate in another. These and other findings suggest that, at least in some cases, cardiac fibroma is a manifestation of a more extensive developmental disorder. PMID- 2250169 TI - Brain amino acid contents are dissimilar in sporadic and Guamanian amyotrophic lateral sclerosis. AB - Amino acid contents were measured in autopsied brains of five Guamanian patients with amyotrophic lateral sclerosis (ALS) or parkinsonism-dementia. Absence of the glutamate deficiency and taurine excess characteristic of sporadic ALS suggest that, despite clinical similarities, Guamanian ALS is a different disorder from sporadic ALS. PMID- 2250170 TI - Acute endothelial swelling is induced in endoneurial microvessels by ischemia. AB - Structural alterations of endoneurial microvessels occur in diabetic neuropathy and are statistically associated with severity of nerve fiber loss and teased fiber abnormality. It is therefore hypothesized that the microvessel alterations may cause or contribute to pathologic alterations of nerve fibers in diabetic neuropathy, possibly through hypoxic injury. The mechanism of the microvessel change in diabetic neuropathy is unknown. The role of microvessels and details of microvessel structure in other possible ischemic neuropathies has not been studied completely. Already there is evidence that hypoxia induces endothelial swelling but this has not been characterized or quantitated in nerve. To determine the acute morphologic effect of ischemia on ultrastructural features of transverse profiles of endoneurial microvessels major pelvic arteries were ligated in rats. At 36 h mean lumen and mural areas were greater in ischemic than in control nerves. All components (endothelium, pericytes and basement membrane) were on average greater in ischemic than controls. The greatest increase was in endothelial cells. In these cells swollen mitochondria were abundant. This study demonstrates that acute ischemia induces swelling of the cells and organelles of endoneurial microvessels. PMID- 2250171 TI - Kynurenic acid synthesis by human glioma. AB - Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40, 200 or 1000 microM L-kynurenine, the immediate bioprecursor of KYNA, freshly prepared tissue slices in a dose-dependent fashion produced KYNA which was detected in the incubation medium. De novo synthesized KYNA was identified by several chromatographic procedures. Astrocytomas produced significantly more KYNA than glioblastomas. PMID- 2250172 TI - GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice. AB - We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity. PMID- 2250173 TI - Calcitonin gene-related peptide and calcitonin immunoreactivity in brain and spinal cord in Alzheimer-type dementia. AB - Calcitonin gene-related peptide (CGRP) and calcitonin (CT) immunoreactivity were measured in hypothalamus, parahippocampal gyrus, pituitary and grey matter of the posterior and anterior spinal cord from five to six cases of Alzheimer-type dementia (ATD) and from five to six controls. CGRP was slightly increased and choline acetyltransferase decreased in the anterior grey of ATD spinal cord. No other significant differences were observed between the levels of the two peptides in the ATD and control tissues, even in the parahippocampal gyrus and posterior grey of the spinal cord which had reduced choline acetyltransferase activity in the ATD cases. These results show that CGRP and CT are not affected in ATD, either as a consequence of a direct effect on peptidergic neurons or secondary to the loss of choline acetyltransferase activity. PMID- 2250174 TI - Pre-mortem diagnosis of Creutzfeldt-Jakob disease by detection of abnormal cerebrospinal fluid proteins. AB - Creutzfeldt-Jakob disease (CJD) may be difficult to diagnose early or when it has an atypical presentation. We describe two patients with progressive dementia in whom the results of diagnostic brain biopsies were unhelpful. Spinal fluid from these patients, analyzed by two-dimensional electrophoresis, contained two abnormal proteins (Nos. 130 and 131, with relative molecular masses of 26,000 and 29,000 daltons and isoelectric points of 5.2 and 5.1). These findings suggested a provisional diagnosis of Creutzfeldt-Jakob disease, which was confirmed in both patients at autopsy. Detection of these abnormal cerebrospinal fluid proteins appears to be a valuable laboratory adjunct in evaluating patients with an unexplained progressive dementia. PMID- 2250176 TI - Somatic reversion/suppression of the mouse mdx phenotype in vivo. AB - The mdx mouse has a myopathy caused by dystrophin deficiency, and is therefore biochemically and genetically homologous to human Duchenne muscular dystrophy. While mdx mouse muscle shows no dystrophin by immunoblotting, a very small percentage of myofibers appear clearly dystrophin-positive by immunofluorescence microscopy. We have characterized these rare positive-staining fibers, and conclude that they are indeed expressing dystrophin despite a nonsense mutation within the dystrophin gene. Thus, the dystrophin-positive fibers probably represent somatic reversion or suppression of the mdx mutation. Cardiac muscle and skeletal muscle from mdx mice showed dramatically different patterns of dystrophin-positive cells. However, this difference is expected given the apparent clonal nature of the reversion/suppression events, the inability of cardiac muscle to regenerate, and other differences in the developmental programs of myofibers and cardiocytes. The prevalence of dystrophin-positive cells in mdx cardiac muscle was determined to be approximately 2 x 10(-5). The observed prevalence of dystrophin-positive cardiocytes in the mdx mouse is a possible estimate of the somatic reversion rate of the mdx mutation in vivo. PMID- 2250175 TI - Electrical myotonia and cataract in X-linked muscular dystrophy (mdx) mouse. AB - An X chromosome-linked mouse mutant (mdx) has been investigated as an animal model of Duchenne's muscular dystrophy, and has been found to have the same defect of dystrophin in the muscle surface membrane. Intracellular recordings from the mdx mouse hemidiaphragm preparations revealed low resting membrane potentials and electrical myotonia which occurred at the time of microelectrode insertion and withdrawal. Electrical myotonia of the mdx mouse was observed in 30 50% of the impaled muscle fibers at low temperature, which decreased to only 7.8% at 37 degrees C. Electrical myotonia of mdx mice was not abolished by (+) tubocurarine. Though there was no behavioral myotonia in mdx mice, repetitive bursts of action potentials in mdx mice were based on the abnormalities of the muscle membrane since neuromuscular blockade did not abolish the repetitive bursts. Also close observation of the lenses of mdx mice revealed cataracts from the newborn stage to the adult age. Slit lamp examination of the lenses of the mdx mice revealed nuclear cataracts followed by anterior subcapsular cataract as they grew. The cataract of mdx mice is different from that of myotonic dystrophy which is usually posterior subcapsular. PMID- 2250177 TI - Detection of mycobacterial antigen in cerebrospinal fluid: diagnostic and prognostic significance. AB - Inhibition enzyme-linked immunosorbent assay (ELISA) was standardised to quantitate circulating mycobacterial antigens in cerebrospinal fluid (CSF) specimens. Of the 40 patients with clinical diagnosis of tuberculous meningitis, the assay was found to be positive in 26 patients. In a control group of 42 patients with non-tuberculous neurological diseases the assay was negative. The assay showed a sensitivity of 65 and 100% specificity for tuberculous meningitis. In 8 patients with tuberculous meningitis receiving chemotherapy, multiple CSF examinations were subjected to this assay. The antigen concentration showed a gradual decrease between 3 and 4 weeks after the commencement of antituberculosis chemotherapy. There was a positive correlation between clinical recovery and antigen concentration. Detection of mycobacterial antigen in CSF specimen by inhibition ELISA has not only diagnostic utility but also could be applied to monitor antituberculosis chemotherapy in patients with tuberculous meningitis. The assay is reproducible and feasible for routine immunology laboratory. It also could be considered as a diagnostic aid when repeated bacteriological cultures are negative in CSF specimens of patients with tuberculous meningitis. PMID- 2250178 TI - Measurement of cerebral blood flow by the stable xenon computerized tomography method. AB - Measurement of cerebral blood flow (CBF) by computerized tomography (CT) is a three-dimensional method with better spatial resolution than the two-dimensional methods. Its principle was first described by Drayer et al. in 1978, with stable xenon (Xes) as CBF indicator. CBF quantitation is based on Fick's principle transformed by Kety and Schmidt when the indicator is a diffusible inert gas. Xes concentrations in cerebral parenchyma and arterial blood are the initial parameters in Kety's equation; they are expressed as variations in attenuation coefficient. Examinations are performed with a Somatom DRH (Siemens) apparatus. Xes (35%) is inhaled from a closed circuit ventilation system which enables xenon to recirculate. From a console connected to the inhalator the operator can command gas preparation, start examination, acquire and transfer data. A reference ("native") section is cut at the site chosen on the topogram. Twelve sections, each 8 mm thick, are then performed while the patient inhales, during 6 minutes, the mixture: air-35% xenon + 65% oxygen. The series of images which enable the CBF parametric image to be calculated is treated in four stages: 1. Xenon concentrations in arterial blood are calculated from the Xes values measured in the air exhaled at the end of expiration. 2. All contrasted sections are visualized on the image monitor after subtraction of the background noise. 3. The CBF parametric image is calculated by Koeppe's optimization method (linear calculation of least squares), using a PDP 11/44 processor. 4. The CBF parametric image is treated to give the CBF value expressed as ml.100 g.min. The method has its limitations: it depends on the limited signal/noise ratio and on the patient's complete immobility; cerebral metabolic rates cannot be measured. But these limitations are largely outweighed by major advantages: the CT/Xes method is non-invasive, safe and reproducible. Owing to its excellent spatial resolution, it provides very accurate maps of superficial and deep regional blood flows. As it measures very low blood flows and can give partition coefficient values, it is of considerable help in the study of ischaemic and degenerative cerebral pathologies. PMID- 2250179 TI - Radio-functional analysis of the cervical spine using the Arlen method. Part Three: Post-traumatic syndromes. A statistical analysis of 480 subjects. AB - The purpose of this study was to determine the differences in patterns of cervical mobility diagrams obtained by the Arlen method in a control population of 240 subjects and in a group of 240 patients who had previously sustained an indirect cervical trauma. The characteristics of antero-posterior mobility of the cervical spine in the control population and their variations due to age and sex are summarized. A statistical study is devoted to the amplitudes of the different vertebral segments during flexion and extension. The authors have tried to elucidate the functional features of the injured spine in its totality and at different levels in both flexion and extension. The two groups were compared in an analysis of spinal dysfunctions (hypomobility, loss of mobility, paradoxical mobility). PMID- 2250180 TI - Mucoceles of the sphenoidal sinus. Report of six cases and review of the literature. AB - Six personal cases of mucocele of the sphenoidal sinus are reported, and 124 cases from the literature are reviewed. Sphenoidal sinus mucocele is a benign and rare lesion which has long been unrecognized. Clinical features include fronto orbital pain, oculomotor palsies, loss of visual acuity, exophthalmos and anosmia. Our series is of particular interest since four of our six patients presented with endocrine disorders. Recent advances in neuroradiological methods should rapidly lead to the correct diagnosis. Treatment consists of aspiration and drainage of the mucocele via a trans-sphenoidal approach. The results are good, and ophthalmoplegia usually subsides. In our experience, endocrine disorders do not always respond to treatment. The prognosis of sphenoidal sinus mucocele depends on the preoperative duration of the loss of visual acuity. PMID- 2250181 TI - Apparently primary malignant melanoma of the cerebellopontine angle. One case. AB - We report a case of primary malignant melanoma of the cerebellopontine angle. This tumour showed RMI features that were totally different from those reported for secondary melanomas, and therefore its nature could not be suspected before surgery. Intracranial primary melanomas are so rare that no other published case is available for comparison, and our tentative explanations for the atypical RMI signals cannot be supported by evidence from the literature. PMID- 2250182 TI - MRI in the diagnosis of Cockayne's syndrome. One case. AB - Computerized tomography (CT) and magnetic resonance imaging (RMI) showed cortico subcortical atrophy as well as calcification of the basal ganglia and the cerebellar dentate nuclei in a patient presenting with cerebellar syndrome. RMI was particularly useful in imaging the demyelination of the periventricular white matter and the subcortical U fibres. A diagnosis of Cockayne's syndrome was made. This is an extremely rare hereditary disease of unknown pathogenesis. Defective recovery of DNA synthesis has been suggested. PMID- 2250183 TI - Ultrastructural correlates of meiotic maturation in mammalian oocytes. AB - Immature mammalian oocytes reside in ovarian follicles with junctionally coupled granulosa cells. When released from a currently undefined meiotic arresting influence, these oocytes resume meiosis to progress from late diplotene (germinal vesicle stage) through the first meiotic division to metaphase II. Oocytes remain at metaphase II until fertilization activates them to complete meiosis. This review summarizes ultrastructural events that occur during meiotic maturation in mammals. Developmental correlates that promise a clearer understanding of regulatory mechanisms operating to control maturation are emphasized. By use of TEM of thin sections, freeze-fracture analysis, and replicated oocyte cortical patches, we demonstrate stage-specific changes in the oocyte nucleus, reorganization of cytoplasmic organelles, correlations between oocyte maturational commitment and the junctional integrity of associated granulosa cells, and definition of the components comprising the oocyte cortical cytoplasm. PMID- 2250184 TI - Morphology of mammalian sperm membranes during differentiation, maturation, and capacitation. AB - The mammalian spermatozoon is a highly polarized cell whose surface membrane can be divided into five functionally, structurally, and biochemically distinct domains. These domains are formed during spermatogenesis, continue to be modified during passage through the epididymis, and are further refined in the female reproductive tract. The integrity of these domains appears to be necessary for the sperm to perform its function--fusion with the egg and subsequent fertilization. The domains can be identified morphologically by their surface contours and texture, the content, distribution, and organization of intramembranous particles after freeze-fracture, and by the density of surface and cytoplasmic electron-dense coatings in thin sections. By using a variety of labels that stain carbohydrates (lectins), lipids (filipin and polymyxin B), and monoclonal antibodies to specific membrane constituents, the biochemical composition of these contiguous membrane regions has also been partly elucidated. We review here what is known about the structure, composition, and behavior of each membrane domain in the mature sperm and include some information regarding domain formation during spermatogenesis. The sperm is an excellent model system to study the creation and maintenance of cell polarity, granule exocytosis, and fertilization. Hopefully this review will provide impetus for future studies aimed more directly at addressing the relationship of its morphology to its functions. PMID- 2250186 TI - Occurrence and developmental consequences of aberrant cellular organization in meiotically mature human oocytes after exogenous ovarian hyperstimulation. AB - The extent to which fertilization failure in in vitro inseminated human oocytes obtained from hyperstimulated ovaries was associated with alterations in cellular structure and cytoplasmic organization was examined by a combination of DIC, fluorescence, time-lapse video, and transmission electron microscopy. Detailed analysis of meiotically mature preovulatory (uninseminated) oocytes, and of oocytes that failed to fertilize in vitro, indicated that between 10% and 15% of grossly normal-appearing MII-stage oocytes displayed one of the following cellular perturbations: 1) a subtle change in organelle distribution, 2) a small region(s) of intracellular cytolysis, 3) a massive aggregation of SER tubules, 4) an accumulation of vesicles presumed to be of SER origin, 5) a change in the structural organization of the cortical cytoplasm and overlying plasma membrane, 6) a sudden and rapid internalization of perivitelline fluid by means of an apparently aberrant process of endocytosis, and 7) a premature and partial exocytosis of cortical granules. The description of these disorders is discussed with respect to the developmental consequences for the oocyte. PMID- 2250185 TI - Cellular and developmental biological aspects of bovine meiotic maturation, fertilization, and preimplantation embryogenesis in vitro. AB - Cellular aspects of reinitiated meiosis, fertilization, and early preimplantation embryogenesis in the bovine species were examined under in vitro conditions. An analysis of the cytoplasmic distribution of mitochondria, lipid droplets and vesicles in over 5,000 living GV-stage oocytes, with subsequent examination by electron microscopy, indicated that the organization of cytoplasm was pleomorphic and that five distinct cellular phenotypes could be identified. Inspection of oocytes during the resumption of arrested meiosis in vivo and in vitro demonstrated that the subcellular organization of the bovine oocyte cytoplasm remains unchanged during maturation to metaphase II. The influence of culture conditions and media on the frequency of maturation, cytoplasmic organization, fertilizability, and early preimplantation embryogenesis was also determined. The findings indicate that meiotic maturation and fertilization in the bovine species can occur at high frequency under comparatively simple and defined conditions. However, the acquisition of developmental competence for fertilization, and the ability of the egg to develop progressively after fertilization appears to be related to the organization of the cytoplasm at the GV stage. The relationship between cytoplasmic organization and conditions of maturation, fertilization, presence or absence of cumulus cells, and the acquisition of developmental competence is discussed with respect to 1) cell biological aspects of mammalian oocyte maturation, 2) the potential influence of extrinsic factors (e.g., differential intrafollicular biochemistry and morphophysiology) on subcellular organization of the GV-stage oocyte, and 3) the finding that morphologically equivalent bovine embryos derived from the in vitro fertilization of in vitro matured oocytes may be developmentally heterogeneous. The studies also revealed that nuclear and cytoplasmic aberrations which could preclude normal embryogenesis can develop shortly after fertilization. The significance of this finding with respect to cytoplasmic phenotype of the oocyte and conditions of maturation, fertilization, and early embryo culture is discussed. PMID- 2250187 TI - Use of microwave fixation in the preparation of cell cultures for observation with the scanning electron microscope. AB - This paper describes a method for primary fixation of cultured cells for scanning (SEM) and transmission (TEM) electron microscopy using microwaves alone. This method of fixation takes 8 seconds and is therefore quicker and less expensive than conventional fixation techniques. The preservation of cell morphology is excellent and cultures of mammalian immune system cells and peripheral nervous tissue have been examined using this fixation. PMID- 2250188 TI - Evaporation during preparation of unsupported thin vitrified aqueous layers for cryo-electron microscopy. AB - Evaporation of water cannot be fully avoided when an unsupported thin vitrified film of an aqueous suspension is prepared for cryo-electron microscopy. This results in increasing concentration of solute which could affect the observed material. We have quantitatively studied this effect by measuring the contrast of polystyrene spheres in a metrizamide solution. The drying effect is generally negligible when specimens are prepared on a hydrophilic perforated support but it is frequently important when hydrophobic films are used instead. A flow of humid air, double blotting with minimal exposure of the thin liquid film to the atmosphere, or an automatic plunger optimizing the blotting conditions are simple methods for reducing drying effects. With this third device acting on a hydrophilic supporting film, the increase of solute concentration is limited to less than 20%. PMID- 2250189 TI - Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. AB - An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues. PMID- 2250190 TI - Sequence analysis of amplified t(14;18) chromosomal breakpoints in B-cell lymphomas. AB - We have explored different strategies for sequencing of major breakpoint (mbr) junctional regions in t(14;18) chromosomal translocations--the most frequent chromosomal abnormality observed in B-cell lymphomas. We demonstrate that coupling of the preparation of single-stranded DNA by asymmetric polymerase chain reaction (PCR) and direct sequencing is the method of choice for the rapid and precise determination of clone-specific bcl-2/JH fusion gene sequences. The rapidity, relative ease, and accuracy of the technique, described for the nucleotide sequence analysis of mbr t(14;18) breakpoints, permits the analysis of a relatively large number of samples and should be considered as part of the clinical evaluation of lymphoma patients. Furthermore, by providing sequence information of clone-specific DNA regions, the procedure should reduce the risk of false-positive results from PCR. PMID- 2250191 TI - A genotypic study of low grade B-cell lymphomas, including lymphomas of mucosa associated lymphoid tissue (MALT). AB - Genotypic analysis has led to the implication of certain oncogenes in the pathogenesis of specific groups of non-Hodgkin's lymphoma. Rearrangements of c myc are associated with Burkitt's lymphoma and of bcl-2 with centroblastic/centrocytic lymphoma. Rearrangement of bcl-1 has yet to be associated with a specific group of lymphoma. In this study DNA from 62 cases of low grade B-cell lymphoma, classified using the Kiel classification, were analysed by Southern blotting and hybridization with probes to bcl-1, bcl-2, and c-myc. Rearrangements of bcl-2 were found in a proportion of centroblastic/centrocytic lymphoma comparable to other published studies. Rearrangement of c-myc was not found in any case studied. Bcl-1 rearrangement was found in 2/9 cases of B-CLL, and 3/6 cases of centrocytic lymphoma. This incidence of bcl-1 rearrangement in centrocytic lymphoma suggests that it is a characteristic change. No rearrangement of bcl-1, bcl-2 or c-myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B-cell lymphoma, lymphomas of MALT comprise a distinct entity. PMID- 2250192 TI - Distribution of type I collagen in human kidney diseases in comparison with type III collagen. AB - The distribution of type I collagen in normal and diseased renal tissues was studied using immunofluorescence and immunoelectron microscopy, and was compared with that of type III collagen. In normal human kidneys, a monoclonal antibody against type I or type III collagen reacted with the renal interstitium, but not with the intra-glomerular structures. In various types of glomerulonephritis, immunofluorescent staining for type I collagen was positive in the fibrocellular and fibrous crescents, sclerosed glomeruli, and infrequently within the glomerular mesangium. In the crescents and sclerosed glomeruli, type I collagen was co-localized with type III collagen. The staining intensity of type I collagen in those areas was generally stronger than that in the interstitium. Mesangial staining for type I collagen was present within the glomeruli, particularly with a marked mesangial matrix increase, but was less in amount and frequency compared with type III collagen staining. These findings indicate that the fibrosclerotic process in damaged glomeruli is accompanied by the appearance of interstitial collagens, and that participation of type I collagen is prominent in crescent organization and global glomerular sclerosis, but is less frequent in mesangial expansion, compared with type III collagen. PMID- 2250193 TI - Analysis of the position of segmental lesions in glomeruli in vasculitic-type glomerulonephritis and other disorders. AB - A method was developed of plotting the position of segmental lesions in glomeruli on histological sections of kidney. Using a Leitz Imagan semi-automatic image analyser, the outline of lesions was traced, as was the outline of Bowman's capsule. The centre of gravity of a lesion, computed by the image analyser, was plotted with reference to the line through the hilum and the centre of gravity of the glomerulus, by taking its angle to that line and its proportional distance between that line and Bowman's capsule. Points representing all lesions were transferred onto a circle graphically representing a glomerulus. Lesions in 11 renal biopsies with the glomerular tip lesion were clustered at the tubular origin. Lesions in four necropsy kidneys from patients with one kidney were clustered at both the vascular pole and the tubular origin. Lesions in 13 renal biopsies with acute vasculitic-type glomerulonephritis were shown to be randomly scattered by nearest-neighbour analysis, after allowance had been made for an edge effect due to the method of plotting lesions and for an area where the arterioles passed through Bowman's capsule. Scientific analysis of the position of segmental lesions is possible and has confirmed previous suggestions that there are at least three general sites in which these lesions can be distributed in glomeruli: at the tip, at the vascular pole, and randomly. PMID- 2250194 TI - Reduction of major histocompatibility complex class I antigens on invasive and high-grade transitional cell carcinoma. AB - We examined immunohistologically the expression of major histocompatibility complex (MHC) class I and II antigens, which play important roles in immune reactions, on transitional cell carcinoma (TCC). When stained with monoclonal antibody W6/32 against class I antigens, reduced staining was observed in 34 of 46 TCCs and was virtually absent in 15 of these. The cases showing reduced staining were much more frequent (29 of 34) in high- to moderate-grade than in low-grade TCC. Furthermore, class I antigens were reduced in 18 of 19 invasive TCCs, but in 16 of 27 superficial TCCs. Thus, the reduction of class I antigens was correlated significantly with a decreased degree of tumour cell differentiation and the presence of invasion. Class II antigens on TCC showed variable expression and were not related to tumour grade or stage. PMID- 2250195 TI - Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection. AB - The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0 3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post transplant biopsies may also be useful as an adjunct to conventional histological diagnosis. PMID- 2250196 TI - Autopsy demonstrations to medical students: audit by questionnaire. PMID- 2250197 TI - Integrin cell adhesion molecules and colorectal cancer. PMID- 2250198 TI - The polymerase chain reaction: miracle or mirage? A critical review of its uses and limitations in diagnosis and research. AB - Since publication of the polymerase chain reaction (PCR) technique in 1985 (Saiki et al. Science 1985; 230: 1350-1354), there has been an explosion of reports on its use in medicine and science. We critically review its use both as a diagnostic technique and as a research tool, and show the pathologist how to evaluate PCR data and how to avoid the pitfalls of overinterpretation. We discuss the value of PCR in the characterization of genetic defects, prenatal diagnosis, carrier testing, HLA typing, detecting micro-organisms, identifying activated oncogenes, and in the characterization of leukaemias and lymphomas, and summarize the main applications in biomedical research. PMID- 2250199 TI - C & S C Folklore. 2. Einstein's last contribution to surface chemistry. PMID- 2250200 TI - The influence of charged lipids on the flocculation and coalescence of oil-in water emulsions. II: Electrophoretic properties and monolayer film studies. AB - The influence of calcium ions on the electrophoretic properties of phospholipid stabilized emulsions containing various quantities of the sodium salts of oleic acid (SO), phosphatidic acid (SPA), phosphatidylinositol (SPI), and phosphatidylserine (SPS) was examined. The critical flocculation concentration of calcium corresponded to a critical zeta potential in all but one of the systems. Systems of approximately equal zeta potential in 0 mM Ca++ had different zeta potentials in dilute solutions of Ca++. A comparison of emulsions of similar polydispersity suggests that these differences may be largely related to differences in particle size and surface area of the emulsions. The influence of Ca++ on the monolayer properties of mixed films containing phosphatidylcholine (PC) with either SPA or SO was also examined at the air-water interface. Films containing PC with SPA were more expanded on a subphase containing calcium compared to a subphase with no calcium. In addition, the compression of films containing PC with SO demonstrated two collapse pressures while SPA was relatively more miscible in the film. This suggests that phase separation of interfacial lipids occurs more easily in systems containing PC and SO. These results may help to explain differences in the flocculation and coalescence of emulsions stabilized by lipid films of different composition. PMID- 2250201 TI - Steam sterilization-in-place technology. AB - Steam sterilization-in-place (more commonly known by its acronym as SIP) is coming into wider usage within the pharmaceutical and biotechnology industries as firms endeavor to increase the level of sterility assurance associated with those products made by aseptic processing. Despite this increase in interest, sterilization-in-place has not been given the attention its growing importance appears to warrant. The intent of this presentation is to define the overall concepts involved with the application of SIP technology and review how these concerns affect specific systems. PMID- 2250203 TI - Validation and environmental monitoring of aseptic processing. Committee on Microbial Purity. AB - The many different checkpoints concerning the complementary activities of validation and monitoring of aseptically processed pharmaceutical preparations are described. The features are based on the official and current GMP guidelines. These are outlined in practical terms according to the personal experience of the authors and manufacturing specialists who were consulted. PMID- 2250202 TI - Eliminating interferences in a compendial test for oxidizable substances in water. AB - The United States Pharmacopoeia (USP) uses acidified potassium permanganate to test for dissolved organics in pharmaceutical-grade water. In the test, a standard permanganate concentration is added to a boiling, acidified water sample. Visually inspecting the sample for residual permanganate determines whether the sample passes (pink color remains) or fails (pink color disappears) the test. The permanganate redox chemistry is complex, however, and test samples are prone to developing suspended particulate and colors other than pink. Forming hazy or off-colored solutions interferes with the subjective end point determination according to the USP test. We report two alternative end point determinations that essentially eliminate interferences from the compendial test method. The first alternative involves recording a uv-visible spectrum of the reduced permanganate test solution. Residual permanganate shows three distinct absorbance maxima at 510, 526, and 545 nm. It is straightforward to differentiate the characteristic permanganate fingerprint from the broad, lower-wavelength extinction that results from interfering substances. The second alternative involves filtering the reduced permanganate test solution through sintered glass. This filtration step removes manganese oxides and other colloidal particles that contribute to haze and off color formation in test samples. Visually inspecting the filtrate for residual pink color remains the end point determination for the test method. A third alternative method, namely spectrophotometric determination of permanganate loss rate constants is not a suitable alternative owing to a strong dependence of permanganate reduction rate on organic substrate structure. PMID- 2250204 TI - Prediction of water vapor transport rates across polyvinylchloride packaging systems using a novel radiotracer method. AB - A radiotracer method is used to study the transport properties of water vapor in polyvinylchloride (PVC), a plastic commonly used in the packaging of parenteral solutions. Water vapor transport across a PVC film appears to be Fickian in nature. Using the steady-state solution of Fick's second law and the permeability coefficient of water vapor across the PVC film obtained using the described method, the predicted water vapor transport rate (WVTR) for a parenteral solution packaged in PVC is in reasonable agreement with actual WVTR as determined by weight loss under precisely controlled conditions. PMID- 2250206 TI - Aseptic validation of a form/fill/seal installation: principles and practice. PMID- 2250205 TI - Interaction of rubber closures with powders for parenteral administration. AB - The migration of volatile components into the headspace of vials sealed with rubber closures is a potential source of haze formation in solutions of reconstituted powders for parenteral administration. Different types of vial closures were examined to determine their propensity to release volatile compounds. It was possible to accumulate the volatiles in a cold trap by means of thermal desorption and dynamic headspace. Gas chromatography coupled with mass spectrometry was then used to characterize the volatiles isolated. Components found in the headspace of butyl and halogenated butyl rubber closures included saturated hydrocarbons, unchlorinated or chlorinated olefins, alkylbenzenes, and low molecular weight polydimethylsiloxanes. PMID- 2250207 TI - Teacher characteristics and competencies related to substance abuse prevention. AB - Teacher characteristics and competencies perceived as beneficial for preventing substance use among students were identified through a literature search, review of existing prevention curricula, and consultation with state and local experts. These qualities were integrated into a questionnaire and administered to acknowledge professionals in the substance use and abuse arena who were affiliated with universities, public schools, and prevention/intervention agencies. A factor analysis yielded six constructs which were then scaled, examined for psychometric appropriateness, and subsequently employed to quantify perceptions of importance. Teacher-Student Relations emerged as the most important aspect of teacher comportment, followed by knowledge associated with Human Behavior, Substances, User Recognition and Referral, Prevention Curricula, and Legal Issues. These findings are encouraging in that the characteristics and skills perceived as important to prevention can be developed in both pre- and in service teacher training. PMID- 2250208 TI - Peer cluster theory and adolescent drug use: a reanalysis. AB - Peer cluster theory hypothesizes that peer drug association has a direct effect on adolescent drug use. In turn, peer drug associations are influenced by familial factors (sanctions and strength) and individual variables (religious identification, school adjustment). Oetting and Beauvais evaluated peer cluster theory in a cross-sectional survey of 415 high school students [1]. We hypothesized, evaluated, and found support for an alternative model in which poorer school adjustment was specified as a consequence of drug use, peer drug associations, lack of family sanctions against drug use, low religious identification, and absence of family strength. This reanalysis illustrates that interpretations of structural equation modeling results from cross-sectional data are especially problematic. PMID- 2250209 TI - Evaluation of a comprehensive elementary school curriculum-based drug education program. AB - This study was designed to evaluate the effectiveness of a province-wide chemical abuse prevention education program for grades two through six. Two separate studies were conducted. Study 1 measured pre- and post-scores on a test with 1101 experimental and 991 control subjects in a quasi-experimental design. Study 2 surveyed 500 elementary school teachers on their opinions and practices regarding drug education, and on the prevalence of the program in schools. The study found that: 1) students had a high initial knowledge level; 2) students showed modest but statistically significant knowledge gains for urban schools and grades three, four, and five of rural schools; 3) the program was most effective with students with a low base knowledge; 4) an estimated 20 to 30 percent of Manitoba elementary teachers had been in-serviced and/or were using the program across the province; and 5) the program was received well among teachers. PMID- 2250210 TI - College students' definitions of social and problem drinking. AB - College students (N = 276) completed surveys describing two common drinking situations. One scenario described a student alone in an apartment after a weekday class; the other, the same student at a weekend party. Sex of the drinker in the scenario was systematically varied. Students estimated the number of drinks a social drinker and a problem drinker would have in each situation. Results indicated that: 1) definitions of social and problem drinking are strongly influenced by drinking context, and 2) male and female subjects estimated that problem drinkers of the opposite sex drank more than problem drinkers of their own sex. Problem drinkers were regularly estimated to consume three to four more drinks than the subject would in the same situation. Implications for education and prevention are discussed. PMID- 2250211 TI - The Marihuana Perception Inventory: the effects of substance abuse instruction. AB - This article reports the latest results of a continuing effort to develop a perceptual inventory of factors associated with the onset of marihuana use among youths and young people. In addition to better understanding why adolescents begin using marihuana, the inventory is intended to assist drug educators target their programs. This phase studied 617 students in three Midwest school districts prior to and after substance abuse instruction to determine the relationship between perceptions and demographic characteristics, and to learn if substance abuse instruction was related to changes in the student's perception of the relationships. Factor analysis again revealed a five-factor solution. All thirty four inventory items were included in the final solution. Items appeared to group themselves among the scales in a fashion similar to that found in prior studies. However, the larger sample size permitted refinement of the scales: Maturational Difficulties; Excessive Pressure; Parental Failings; Rebelliousness; and Societal/Institutional Weaknesses. The inventory appears to be remarkably stable across demographic characteristics. Significant differences between pretest and posttest scores indicated that students perceived less of a relationship between Maturational Difficulties, Excessive Pressure, and Societal/Institutional Weaknesses and the onset of marihuana use after instruction, and more of a relationship between Parental Failings and the young person's decision to begin using marihuana. It appears that instructional programs can be expected to at least contribute to changes in perceptions concerning the relationship between societal and familial factors and the onset of marihuana use. PMID- 2250212 TI - A comparative analysis of factors influencing smoking behaviors of college students: 1963-1987. AB - A questionnaire relating to smoking behavior was developed and administered to 3,786 college students who were attending introductory personal health classes at selected colleges in the state of Oregon during the 1963-64 school year. Analysis of the data was not completed until 1987 (twenty-three years later) at which time the data cards were discovered in storage. During the 1986-87 school year a modified questionnaire was developed and administered to 863 college students attending introductory personal health classes at three of the same four universities that were utilized in the 1963-64 study. The study addressed the smoking behavior of an often neglected population of older adolescents and younger adults over a time period of twenty-three years. Stepwise logistic regression equations were used to determine the set of variables that best accounted for smoking status in 1963-64 and 1986-87. Results indicated that the variables that increased the probability of an individual smoking in 1963-64 did not increase the probability of an individual smoking in 1986-87. The characteristics and behaviors of family members have significantly less influence on the smoking behavior of adolescents and young adults today when compared to adolescents and young adults in 1963-64. PMID- 2250214 TI - Remember the basics. PMID- 2250213 TI - Tobacco prevention in North Carolina public schools. AB - The purpose of this study is to report on the extent of, and organization for, tobacco prevention education in North Carolina Public Schools. Moreover, issues for the diffusion of tobacco prevention curricula are discussed. A questionnaire examining tobacco education practices and curriculum within school districts was mailed to health education representatives in each of the North Carolina public school districts. One-hundred twenty-five usable questionnaires were returned for analysis (125/140 = 89.3%). Of the school districts responding to the survey, 101 (80.8%) reported having adopted a system-wide curriculum which includes tobacco related instruction. Additionally, a large percentage of the school districts with an adopted curriculum were using commercially published materials (85.2%). Large tobacco producing counties in North Carolina were not significantly different than other counties in the adoption or public acceptance of school programs with a tobacco prevention component. However, school systems with an adopted, general tobacco use policy for the district were more likely to have adopted a district-wide tobacco education curriculum. Individual schools were also involved with multiple tobacco prevention curriculum and learning programs. In the sixth, seventh, and eighth grades, the sample reported using a total of twelve different programs. Many of these learning programs lacked necessary elements of effective programs. Key diffusion issues included the impact of multi tobacco curricula use to the introduction of new and effective material, as well as the association between district-wide tobacco use policies and the adoption of curriculum. PMID- 2250215 TI - Teaching materials for pediatric health professionals. AB - Nurses can update their use of pre-op teaching materials with medical playthings. Anatomical dolls, medical puppets and stuffed animals, toys and games, as well as replicas of medical equipment and furniture are now available to demonstrate more clearly to patients what will be happening to them. Using actual medical supplies for supervised play also helps child patients understand procedures, vent feelings and express beliefs. The careful selection or creation of medical toys enhances existing teaching programs. PMID- 2250216 TI - Development and enhancement of self-esteem in children. AB - Self esteem has been recognized as an important factor in a child's development. This literature review explores components of a child's self esteem, the development of self esteem, and roles parents can play in enhancing a child's self esteem. Pediatric nurse practitioners (PNPs) are in an excellent position to help parents understand their child's self esteem development and to assist parents in structuring an environment conducive to this development. Important areas for PNPs to explore with parents include expectations for their children, effective communication techniques, discipline strategies, child-centered guidance, and methods to promote children's autonomy. PMID- 2250217 TI - Pharmacologic treatment of otitis media and sinusitis in pediatrics. AB - Otitis media and sinusitis are common diseases of childhood whose treatment is essential to long-term health. This article presents an update on the microorganisms involved in these two conditions and the selection and appropriate use of antimicrobial drugs for treatment. The issues of prophylaxis of recurrent otitis media and potential vaccines are discussed. In addition, approaches to increase patient compliance are presented, and the role of the nurse in educating parents about the condition and its treatment is discussed. PMID- 2250218 TI - Phototherapy in the home setting. AB - Physiologic jaundice is a self-limiting process affecting approximately 50% of normal-term infants during the first week of life. Phototherapy has proven to be effective in reducing or preventing the rise in bilirubin levels in the newborn when it is related to this natural process. However, phototherapy generally prolongs the length of hospital stay for the jaundiced newborn. The trend toward early discharge and the increase in the availability of highly sophisticated technical equipment designed for home use affords the family the opportunity to actively engage in the decision to take their child home early, thus reducing expenses and time spent in the acute care setting. Home care also allows the family to stay together while caring for the jaundiced newborn and promotes early bonding of all family members, including siblings. This article presents an overview of home phototherapy, focusing on the role and responsibility of the nurse and education of the parent/caretaker. PMID- 2250219 TI - Helping children cope with stress. PMID- 2250220 TI - Adolescent fathers. PMID- 2250221 TI - Year 2000 health objectives. AB - The potential effects of the report reach far into the health care community. This report could mark the beginning of an era of increased preventive health care. How the report is followed-up, however, is the key to the Year 2000 equation. Countless hours of study and countless dollars have, in the past, produced valuable reports similar to the Year 2000 report. Yet, the results of these other reports, because of lack of follow-up, are less than impressive. If the contributions of more than 7000 individuals are to translate to better health for the nation in the year 2000, follow-up measures must be enacted. This is an opportunity for action on the part of NAPNAP and all pediatric nurse practitioners. PMID- 2250222 TI - U.S. Consumer Product Safety Commission. PMID- 2250223 TI - A brief history of pediatric nurse practitioners and NAPNAP 1964-1990. AB - The pediatric nurse practitioner movement began in 1964 and is now 25 years old. Anniversaries are a good time for pausing to look backward and look forward. This brief history reports some early pediatric nurse practitioner adventures and a few of the beginning episodes of the National Association of Pediatric Nurse Associates and Practitioners. These special highlights make a remarkable statement about an elite cohort of nurses. PMID- 2250224 TI - Elucidating the pathogenesis of autoimmune disease: recent advances at the molecular level and relevance to oral mucosal disease. AB - Humoral and/or cellular immune responses directed against self antigen are currently thought to underlie a wide spectrum of systemic and organ-specific human and animal autoimmune diseases. Although the immunopathology of these diseases has been well characterized in most cases, the etiology still remains obscure. In order to gain a more fundamental insight of the abnormal processes leading to autoimmunity, efforts are currently being directed toward defining these diseases at a molecular level. Because of the clinical diversity and immunological complexity of these diseases, several directions are being pursued. Relevant to autoimmune oral disease, this review will focus on antigen processing and recognition (immunoglobulin and T cell receptor genes), the key role of the major histocompatibility complex, and the involvement of the cytokine network. Advances made in these fields have clear relevance for future diagnostic and therapeutic strategies related to autoimmune diseases affecting oral tissues. PMID- 2250225 TI - Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation. AB - Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy. PMID- 2250226 TI - Cytotoxic and immunostimulatory effects of Bacteroides cell products. AB - The etiologic role of Bacteroides in both periodontal and periapical infections has been well documented, with current interest focusing on the specific pathogenic mechanisms involved. The effects of cell fractions derived from Bacteroides gingivalis (BG), Bacteroides intermedius (BI), and Bacteroides asaccharolyticus (BA) have been studied in vitro through: an assessment of the direct cytotoxic effects on human gingival fibroblasts using a tetrazolium dye reduction assay, an evaluation of murine lymphocyte stimulation and interleukin-1 release, and the induction of human lymphocyte-mediated cytotoxicity. Both BG and BI stimulated interleukin-1 release (P less than 0.001), while BA, a nonoral organism, was not significantly active in this respect. Only BG sonicates were able to induce lymphocyte-mediated cytotoxicity (P less than 0.005). All three Bacteroides species demonstrated direct cytotoxic effects on cultured gingival fibroblasts, and these effects were related to the relative protein content and endotoxin activity of the sonicate preparations for each organism. These data show that BG and BI possess factors which may enhance their virulence through activities not shared with BA. PMID- 2250227 TI - LongoVital in the prevention of recurrent aphthous ulceration. AB - LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. The present study was undertaken to investigate prevention of recurrent aphthous ulceration (RAU) during 6 months' daily intake of LV as compared with placebo in a double-blind, randomized clinical, cross-over 1-yr study. The population comprised 29 otherwise healthy minor RAU patients (18 F, 11 M), mean age 36 (18-67), with an estimated average number of recurrences the previous year of 12.8 (3-30). The number of recurrences was significantly reduced on LV the latter 4 of the 6 months (P less than 0.01) where 31% were totally free of recurrences. Subjective all-over evaluation of treatment period was significantly in favor of LV. LV induced no adverse reactions and is the first harmless systemic treatment which has proved better than placebo in the prevention of RAU. PMID- 2250228 TI - Oral senile amyloidosis in senescence accelerated mouse (SAM). AB - Oral senile amyloidosis in senescence accelerated mouse (SAM) was examined for two SAM sublines (P/2/Iw and R/1/Iw) and for various ages by light microscopy, immunohistochemistry, and electron microscopy. The amyloid deposition, identified by green birefrigence following Congo red stain, was observed only in P/2/Iw. In P/2/Iw, no amyloid deposition was found at age 6 months; however, frequency and extent of such deposits increased with advancing age. Distribution of amyloid deposition was as follows: along papillary layers of mucous epithelium in the tongue, the gingiva, the palate, and the buccal mucosa; foci in connective tissues; along vessels, muscles, and minor salivary glands. Immunohistochemically, the amyloid deposition was positive with anti-ASSAM serum being raised against a unique amyloid protein ASSAM which probably induced "senile systemic amyloidosis". P/2/Iw is useful as an animal model of oral senile amyloidosis. PMID- 2250229 TI - Laband syndrome: a case report. AB - A case of Laband syndrome in an 8-yr-old girl is presented. The case is sporadic. The patient manifests enlargement of the soft tissue of the hard palate and the gingiva, which partly or completely covers the crowns of the teeth and macroglossia. The cartilagenous part of the nose and the ears is large and soft. She has synophrys and thick, straight hair. The nails of the fingers and toes are dysplastic. The girl exhibits no other abnormality, except an IQ of 61. PMID- 2250230 TI - Family background and individual measures as predictors of Turkish primary school children's academic achievement. AB - The primary purpose of this study was to predict academic grade point averages (GPAs) of Turki primary school children, using family background and individual measures (sociometric standing, self-reported loneliness, and social efficacy) as predictors. We hypothesized that these two measures would explain the wide variation in GPA for samples differing with respect to sex and paternal education. Regression analyses with male and female subsamples revealed that the background measures explained twice as much variance in GPA, popularity, and loneliness for girls as for boys. Another finding was that the background measures explained a greater proportion of the variance in GPA for children with less- versus more-educated fathers, whereas individual measures explained a greater proportion of the variance for children with more as opposed to less educated fathers. PMID- 2250232 TI - Acceptability of school-based interventions: a replication with a black sample. PMID- 2250231 TI - Enhanced encoding of nonverbal cues in bipolar illness in males. AB - Twenty-five affectively bipolar males were found to possess an enhanced ability to encode nonverbal cues when compared to matched controls. This ability was present during both manic and euthymic phases. PMID- 2250233 TI - Young children's understanding of the shuttle disaster (1986). PMID- 2250234 TI - Cryopreservation of spermatozoa from cynomolgus monkeys (Macaca fascicularis). AB - Three egg-yolk diluents, which have been used successfully in cryopreservation of human spermatozoa, were compared for their ability to protect macaque semen against cryodamage. TEST (Tes + Tris + egg yolk), TEST with 20% skim milk (TSM), and egg yolk-citrate (EYC), each with 3 or 5% glycerol were compared using 12 ejaculates from 6 male cynomolgus macaques. Computer-aided analysis of sperm motion was used to determine the percentage motility (%M), curvilinear velocity (VCL), and linearity (LIN) of spermatozoa after thawing. The supravital stain Hoechst 33258 and a fluoresceinated pea lectin were used to determine the % of viable spermatozoa with intact acrosomes. TSM and TEST were superior to EYC in terms of % M and of % viable, acrosome-intact spermatozoa. TSM and TEST produced equivalent VCL and LIN values, while EYC had clearly reduced VCL and LIN. There were no interactions between diluent and glycerol level. The 3% glycerol level gave superior results to 5% glycerol for %M. EYC, which is widely used for cryopreservation of human spermatozoa, was not suitable for cynomolgus monkey semen. Artificial insemination with semen cryopreserved in TSM resulted in a healthy, full-term infant. PMID- 2250235 TI - Spatial arrangement of the stages of the cycle of the seminiferous epithelium in the Japanese quail, Coturnix coturnix japonica. AB - The spatial arrangement of the stages of the cycle of the seminiferous epithelium of the Japanese quail was investigated by preparing three-dimensional reconstructions of a seminiferous tubule from each of 3 quails. It was found that the stages were not distributed at random, but were arranged in a wave which spiralled helically along a seminiferous tubule. Adjacent stages in space were always adjacent numbers in the cycle of the seminiferous epithelium. Complete spermatogenetic waves were found in which all 10 stages of the cycle were in sequential order. However, in most waves the sequential order of stages was disturbed by the occurrence of modulations. The area of a cellular association varied from 4600 to 41,600 microns 2 with a mean +/- s.e.m. (3 animals) of 17,902 +/- 2614 microns 2. The number of Sertoli cells involved in an association ranged from 4 to 35, with a mean +/- s.e.m. (3 animals) of 13.5 +/- 2.8. The findings support our earlier suggestion that the kinetics of spermatogenesis in the quail are fundamentally similar to the pattern which has been described for mammals. PMID- 2250236 TI - Influence of time of mating and paced copulation on induction of pseudopregnancy in cyclic female rats. AB - The present experiment was designed to examine whether changes occur during the course of behavioural oestrus in the sensitivity of the female to copulatory stimulation and in patterns of sexual behaviour which might influence the likelihood of luteal maintenance. Cyclic female rats were mated on the evening of pro-oestrus (21:00 h) or early on the morning of oestrus (05:00 h) and received either 5 or 10 intromissions from males under conditions which allowed or did not allow pacing of contacts with males to occur. During mating, the levels of sexual receptivity, the timing of sexual mounts from males, and pacing behaviours were measured. The occurrence of pseudopregnancy or pregnancy in each animal was determined by examining vaginal smears for 14 days after mating and by examining the uterus for the presence of fetuses at the end of the experiment. At both mating times, pacing of copulation with males increased the likelihood of prolonged luteal activity. However, females were more likely to become pseudopregnant following non-paced mating at 05:00 h than at 21:00 h the previous evening. Of those females receiving an ejaculation during mating, no difference were seen between groups in the incidence of pregnancy. This change in sensitivity to cervical-vaginal stimulation during oestrus was not associated with changes in sexual receptivity or pacing behaviour. The ability of cervical vaginal stimulation to induce pseudopregnancy therefore increases toward the end of the period of oestrus, but the behavioural mechanisms which regulate receipt of such stimulation remain constant during that time. PMID- 2250237 TI - Failure to maintain interspecific pregnancy after transfer of Dall's sheep embryos to domestic ewes. AB - Over a 3-year period, 32 Dall's sheep (Ovis dalli dalli) embryos were transferred into 24 domestic sheep (O. aries) recipients and 4 were transferred into 2 Dall's sheep recipients. In the first year, none of the 10 O. aries recipients was diagnosed pregnant. In the following 2 years, 9 (37%) of the domestic sheep recipients were pregnant on Day 18, 8 (33%) on Day 40, 6 (25%) on Day 90 and 4 (16%) on Day 120; 1 aborted at Day 125 and another at Day 145. Pregnancies were established only in ewes that had previously been recipients of Dall's sheep embryos. The 2 remaining pregnant sheep were treated with progesterone from Day 125 until the fetuses were determined to be dead at Day 145. Both of the Dall's sheep recipients (Year 2) established pregnancies; 1 live Dall's sheep lamb was born 174 days after mating. No differences in serum progesterone, oestrone, prostaglandin F-2 alpha metabolites or cortisol concentrations could be detected during pregnancy between recipients carrying Dall's sheep embryos, recipients receiving progesterone treatment or domestic ewes carrying domestic sheep pregnancies. Six fetuses were necropsied (1 at Day 125 and 5 at Day 145-146): all fetuses were premature and had various degrees of hydranencephaly. No significant differences were found when cotyledon numbers were compared among domestic ewes carrying Dall's sheep lambs. Dall's sheep ewes lambing naturally and domestic ewes lambing naturally. These results demonstrate that the transfer of Dall's sheep embryos to domestic ewes results in the establishment but subsequent loss of pregnancy and that these losses occur throughout gestation. PMID- 2250239 TI - Progesterone and oestradiol-17 beta concentration profiles throughout the reproductive cycle in harbour seals (Phoca vitulina). AB - Serum samples of harbour seals kept in captivity were analysed for progesterone and oestradiol-17 beta. The hormone profiles obtained were used to describe a complete reproductive cycle. A clear peak in oestradiol values, indicative of ovulation, was followed by elevated concentrations of progesterone. Implantation probably occurred 3-3.5 months thereafter. Progesterone concentrations rose significantly in the last 3-4 months of gestation, whereas oestradiol concentrations gradually increased after implantation. Lactational oestrus was marked by a peak of oestradiol on average 25 days after parturition and lactation lasted 4-5 weeks. Previous pregnancy had a marked influence on the timing of oestrus; females with offspring started a new reproductive cycle about 14 days later than previously non-pregnant seals. No differences in timing of parturition between the 2 groups were observed. This was probably the result of a flexible period of delayed implantation. PMID- 2250238 TI - Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha. AB - Certain strains of mice display an increased frequency of fetal resorption, but little is known about the effector mechanisms involved. We have examined the events associated with lipopolysaccharide (LPS)-induced fetal resorption in mice. Administration of 25 micrograms LPS on Day 12 of gestation resulted in the appearance of tumour necrosis factor-alpha (TNF-alpha) in the amniotic fluid and fetal resorption. Levels of LPS-induced TNF-alpha were reduced by 90% after pretreatment with the TNF-alpha-suppressing drug pentoxifylline (PXF). Treatment of pregnant mice during early gestation with 0.1 micrograms LPS resulted in fetoplacental resorption which was maximal when the LPS was given on Day 8. Resorption induced by 0.1 micrograms LPS on Day 8 of gestation was significantly reduced by pretreatment with PXF. Infiltration of asialo-GM1-positive cells was observed in the decidual-ectoplacental cone area of embryonic units from LPS treated mice. In addition, treatment with anti-AGM1 antiserum prevented the LPS induced resorption. Our results suggest that TNF-alpha and asialo-GM1-positive cells are involved in LPS-induced fetal resorption. PMID- 2250240 TI - Extension of reproductive suppression by pheromonal cues in subordinate female marmoset monkeys, Callithrix jacchus. AB - Pheromonal signals from the dominant female marmoset monkey were implicated in maintaining the suppression of LH secretion and ovulation in socially subordinate females. When subordinate, and reproductively suppressed, female marmoset monkeys were removed from their group without scent contact with their dominant females, subordinate females in control group 1 (N = 8) and control group 2 (N = 5), ovulated 10.8 +/- 1.4 days and 10.4 +/- 0.8 days respectively (mean +/- s.e.m.) after separation. Subordinate females (N = 8) removed from their dominant female and group, but maintained in scent contact only with their dominant females, showed a delay in the onset of ovulation (31.0 +/- 6.4 days) compared with control groups 1 and 2. Plasma LH concentrations of subordinate females during the scent transfer phase were lower than in controls without scent transfer and comparable to those seen whilst the females were subordinates in groups. Contact of subordinate females with olfactory stimuli from dominant females therefore maintains the suppression of both LH secretion and ovulation in socially subordinate female marmosets. Such pheromonal cues provide evidence of a quantifiable link between dominant female marmosets and the maintenance of physiological suppression of reproduction in their female subordinates. PMID- 2250241 TI - Examination for platelet-activating factor production by preimplantation mouse embryos using a specific radioimmunoassay. AB - A specific and highly sensitive radioimmunoassay was used to measure platelet activating factor (PAF) production by preimplantation mouse embryos in vitro. Levels of PAF greater than 1 pg per embryo were not observed in 24-h culture medium from 2-cell embryos, compacted morulae or blastocysts, or in extracts from these embryos. Synthetic PAF added to embryos at the start of culture could be almost totally recovered after the incubation period, indicating negligible degradation of PAF during culture. PAF was also not detected in embryo samples using a washed rabbit-platelet aggregation assay. It can be concluded that mouse embryos do not produce substantial levels of PAF, or any of the biologically active analogues of PAF detected by the assay. PMID- 2250242 TI - Size distribution of luteal cells from pregnant and non-pregnant marmoset monkeys and a comparison of the morphology of marmoset luteal cells with those from the human corpus luteum. AB - The size distribution of marmoset luteal cells was determined on Days 6, 14 and 20 after ovulation in non-pregnant cycles and in early pregnancy. Image analysis was used to estimate the cell diameter of dispersed cells prepared from the marmoset corpus luteum (CL). Steroidogenic cells showed a size distribution consistent with one population of cells. There was a significant increase in mean cell diameter (P less than 0.05) from Day 6 to Day 14 in pregnant and non pregnant animals with no further increase on Day 20. Micrographs of marmoset luteal tissue showed cells of greater than 10 micron containing the organelles typical of steroid-producing cells, and smaller non-steroidogenic cells surrounding the steroid-producing cells. On the basis of microscopy, there were no areas within the CL where cell composition was noticeably different. In contrast, micrographs of human luteal tissue showed two types of steroidogenic cell; most cells were similar to those in the marmoset CL but a smaller population of smaller cells could be distinguished around the periphery and along vascular septa. It is likely that these smaller and larger types of steroidogenic cells are of theca and granulosa cell origin respectively, the two cell populations differing in the degree of electron density and amount of rough endoplasmic reticulum. A distinguishing feature between marmoset and human luteal cells was the shape of the mitochondrian which were considerably rounder in marmoset luteal cells. The origin of steroidogenic cells in the marmoset CL is unclear, although in marmosets and man the luteal cell types display morphological characteristics distinct from the large and small luteal cells described for CL of the domestic ungulates. PMID- 2250243 TI - Tissue concentration, mRNA expression and stimulation of IGF-I in luteal tissue during the oestrous cycle and pregnancy of cows. AB - The expression of IGF-I in bovine luteal tissue was demonstrated by parallel measurement of IGF-I tissue concentration and its mRNA; highest synthesis was observed during Days 12-17 of the cycle and the first months of pregnancy. Tissue levels of IGF-I increased from Days 1-5 to Days 12-17 of the cycle followed by a rapid decrease at luteolysis; there was a continuous decline from early pregnancy until Months 6-9. Microdialysis perfusion experiments with corpora lutea in vitro at Days 8-11 of the cycle revealed a major effect: release of progesterone and oxytocin were highly stimulated in a dose-dependent manner. We suggest that IGF-I could be important in regulating the function of the bovine corpus luteum and may act in an autocrine/paracrine way. PMID- 2250244 TI - Changes in the composition of the hamster zona pellucida after fertilization in vivo but not in vitro. AB - Hamster zonae pellucidae were obtained from follicular oocytes, superovulated eggs, and eggs fertilized in vivo or in vitro. Zonae were labelled with N succinimidyl-3(4-hydroxy,5-[125I]iodophenyl)propionate, and compared on single- and two-dimensional SDS-PAGE. Single-dimensional electrophoresis showed considerable differences between zona categories in the amount of label that they incorporated; follicular zonae incorporated the least label and zonae from eggs fertilized in vivo the most. On two-dimensional electrophoresis, polypeptides from 3 of the 4 zona categories migrated into 4 major groups: two of these groups each with Mr 150,000-250,000 were within the Mr range of ZP1, and two others, at Mr 90,000 and 55,000, appeared to be analogous to ZP2 and ZP3, respectively. The fourth zona category (zonae from eggs fertilized in vivo) showed a changed polypeptide profile as well as incorporating the most label; one of the polypeptides, Mr 150,000-250,000, was undetectable, but a train of Mr 70,000 90,000 polypeptides and a discrete polypeptide at Mr 20,000 were new. Since this changed profile did not occur in zonae from superovulated eggs, or in zonae from eggs fertilized in vitro, a synergism between oviductal factors and factors from the spermatozoon or egg, or both, towards the zona in vivo is indicated. PMID- 2250245 TI - Purines inhibit the development of mouse embryos in vitro. AB - The first cleavage of embryos derived from random-bred, inbred, and hybrid-inbred female mice was not arrested by purines at concentrations as high as 30 microM. Development after the first or second cleavage was arrested by hypoxanthine, adenosine or inosine, but not guanosine. In agreement with previous results, the purine-induced block was reversed when arrested embryos were transferred to purine-free media after 24 h in culture. The cleavage arrest was not due to elevations of cAMP as a result of inhibition of phosphodiesterase activity since similar concentrations of phosphodiesterase inhibitors or dibutyryl cAMP did not block development. Treatment with inhibitors of enzymes that convert IMP to AMP or to GMP did not reverse the hypoxanthine-induced block, thus demonstrating that mitotic arrest is mediated by a mechanism different from the hypoxanthine arrest of meiosis. Thymidine incorporation studies showed that the block did not prevent the onset of DNA synthesis. The results reveal a profound sensitivity to purine inhibition of a cell process that occurs during the first 30 h of mouse embryo development and is necessary for progession through the G2 or M phases of the second or third cleavage. PMID- 2250246 TI - Vasoactive intestinal polypeptide in the PMSG-primed immature rat ovary and its effect on ovulation in the isolated rat ovary perfused in vitro. AB - The immature rat ovary contains VIP immunoreactive nerve fibres sparsely distributed around blood vessels, in the interstitial gland and around follicles. The VIP concentration, measured radioimmunologically, decreased significantly after PMSG treatment (10 i.u.), probably due to ovarian enlargement and oedema, while the total VIP content (total of 0.12 pmol in both ovaries) did not change after PMSG priming. The ovulatory effect of VIP was studied using in-vitro perfused ovaries from immature 28-day-old rats primed with 10 i.u. PMSG. In all ovaries perfused, VIP (10(-7) M) induced ovulations with a rate of 2.33 +/- 0.56. The ovulation rate was significantly lower than that of ovaries stimulated by LH (0.1 microgram/ml) (5.20 +/- 0.86 ovulations per ovary). No synergistic effect on the ovulation rate was seen when LH and VIP were administered together (5.20 +/- 0.49 ovulations per ovary). The results suggest that the neuropeptide VIP may represent one of the local factors involved in the ovulation process. PMID- 2250247 TI - Effects of high-density lipoproteins on storage at 4 degrees C of fowl spermatozoa. AB - Qualitative and quantitative characterization of lipoproteins found in seminal plasma from domestic cocks was performed after isolation by density gradient ultracentrifugation. Trigyceride-rich lipoproteins (very low, intermediate- and low density lipoproteins) were not detectable in seminal plasma. High-density lipoproteins (HDL), identified on the basis of size, chemical composition and protein moiety, were present at a concentration of 66 micrograms/ml. A fraction possibly corresponding to VHDL (very high density lipoproteins, 77% protein, 23% lipid) was also detected but appeared contaminated by a protein-rich opalescent material. Since HDL contains mostly phospholipid and cholesterol, the physiological role of these lipoproteins on the storage of fowl spermatozoa was studied. Replacing seminal plasma with a solution containing chicken HDL at physiological concentration (66 micrograms/ml) had no effect on fertilizing ability of spermatozoa stored at 4 degrees C for 24 h. However, higher concentrations of HDL (560 micrograms/ml) had deleterious effects on spermatozoa stored in vitro. PMID- 2250248 TI - Extension of oestrous cycles and prolonged secretion of progesterone in non pregnant cattle infused continuously with oxytocin. AB - The experimental objective was to evaluate how continuous infusion of oxytocin during the anticipated period of luteolysis in cattle would influence secretion of progesterone, oestradiol and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM). In Exp. I, 6 non-lactating Holstein cows were infused with saline or oxytocin (20 IU/h, i.v.) from Day 13 to Day 20 of an oestrous cycle in a cross over experimental design (Day 0 = oestrus). During saline cycles, concentrations of progesterone decreased from 11.0 +/- 2.0 ng/ml on Day 14 to 2.0 +/- 1.3 ng/ml on Day 23; however, during oxytocin cycles, luteolysis was delayed and progesterone secretion remained near 11 ng/ml until after Day 22 (P less than 0.05). Interoestrous interval was 1.6 days longer in oxytocin than in saline cycles (P = 0.07). Baseline PGFM and amplitude and frequency of PGFM peaks in blood samples collected hourly on Day 18 did not differ between saline and oxytocin cycles. In Exp. II, 7 non-lactating Holstein cows were infused with saline or oxytocin from Day 13 to Day 25 after oestrus in a cross-over experimental design. Secretion of progesterone decreased from 6.8 +/- 0.7 ng/ml on Day 16 to less than 2 ng/ml on Day 22 of saline cycles; however, during oxytocin cycles, luteolysis did not occur until after Day 25 (P less than 0.05). Interoestrous interval was 5.9 days longer for oxytocin than for saline cycles (P less than 0.05). In blood samples taken every 2 h from Day 17 to Day 23, PGFM peak amplitude was higher (P less than 0.05) in saline (142.1 +/- 25.1 pg/ml) than in oxytocin cycles (109.8 +/- 15.2 pg/ml). Nevertheless, pulsatile secretion of PGFM was detected during 6 of 7 oxytocin cycles. In both experiments, the anticipated rise in serum oestradiol concentrations before oestrus, around Days 18-20, was observed during saline cycles, but during oxytocin cycles, concentrations of oestradiol remained at basal levels until after oxytocin infusion was discontinued. We concluded that continuous infusion of oxytocin caused extended oestrous cycles, prolonged the secretion of progesterone, and reduced the amplitude of PGFM pulses. Moreover, when oxytocin was infused, pulsatile secretion of PGFM was not abolished, but oestrogen secretion did not increase until oxytocin infusion stopped. PMID- 2250249 TI - Re-examination of the presence of alpha-lactalbumin in the epididymis of the rat. AB - Using an assay for alpha-lactalbumin in which galactosyltransferase activity was stabilized and a tissue phosphatase inhibitor was present, no evidence was found for alpha-lactalbumin-like activity in rat epididymal tissue, epididymal fluids or medium from cultured epididymal epithelial cells with either glucose or N acetylglucosamine as acceptor. However, when assay conditions were suboptimal, apparent transfer of radioactivity to both acceptors could be demonstrated in the epididymis and other tissues. In these assays the amount of alpha-lactalbumin registered was linearly correlated to the extent of stimulation of alpha lactalbumin added exogenously to tissue extracts as internal standards. When rete testis fluid from rats was used as source of galactosyltransferase under suboptimal conditions, no transfer to glucose was demonstrable in epididymal fluid and an apparent decreased transfer to N-acetylglucosamine could be explained by increases in (pyro)phosphatase activity. Putative alpha-lactalbumin activity in the epididymis may be an artefact of unoptimized assays. PMID- 2250250 TI - Pattern of follicular growth and resumption of ovarian activity in post-partum beef suckler cows. AB - The ovaries of 18 post-partum beef suckler cows were examined daily, using ultrasound, from Day 5 post partum until a normal oestrous cycle was completed. Periods of growth and regression of medium-sized (5-9 mm) follicles were identified before one medium follicle became dominant (single large follicle greater than or equal to 10 mm). The mean (+/- s.e.m.) number of days from parturition to detection of the first post-partum dominant follicle was 10.2 +/- 0.5. The first post-partum dominant follicle ovulated in 2/18 (11%) cows. The interval from calving to first ovulation (mean +/- s.e.m. = 35.9 +/- 3.3 days) was characterized by the growth and regression of a variable number (mean = 3.2 +/- 0.2; range 1-6) of dominant follicles. The maximum diameter of the dominant follicle increased as the cows approached first ovulation (P less than 0.05). Behavioural oestrus was not detected in 16/18 (89%) cows at first ovulation. Following first ovulation, the length of the subsequent cycle was short (mean = 9.7 +/- 0.5 days; range 8-15 days) in 14/18 (78%) cows and was characterized by the development and ovulation of a single dominant follicle. During oestrous cycles of normal length (mean = 20.6 +/- 0.5 days; range 18-23 days) one (N = 2), two (N = 7) or three (N = 8) dominant follicles were identified. The growth rate, maximum diameter or persistence of non-ovulatory dominant follicles before first ovulation or during oestrous cycles were not different (P greater than 0.05). These data show that, in beef suckler cows, follicular development and formation of a dominant follicle occur early after parturition and the incidence of ovulation of the first dominant follicle is low. The number of dominant follicles that develop before first ovulation is variable; first ovulation is rarely associated with oestrus and short cycles are common after first ovulation. It is concluded that prolonged anoestrus in post-partum beef suckler cows is due to lack of ovulation of a dominant follicle rather than delayed development of dominant follicles. PMID- 2250251 TI - Effects of lactational and reproductive status on ovarian follicular waves in llamas (Lama glama). AB - The effects of lactational status and reproductive status on patterns of follicle growth and regression were studied in 41 llamas. Animals were examined daily by transrectal ultrasonography for at least 30 days. The presence or absence of a corpus luteum and the diameter of the largest and second largest follicle in each ovary were recorded. Llamas were categorized as lactating (N = 16) or non lactating (N = 25) and randomly allotted to the following groups (reproductive status): (1) unmated (anovulatory group, N = 14), (2) mated by a vasectomized male (ovulatory non-pregnant group, N = 12), (3) mated by an intact male and confirmed pregnant (pregnant group, N = 15). Ovulation occurred on the 2nd day after mating with a vasectomized or intact male in 26/27 (96%) ovulating llamas. Interval from mating to ovulation (2.0 +/- 0.1 days) and growth rate of the preovulatory follicle (0.8 +/- 0.2 mm/day) were not affected by lactational status or the type of mating (vasectomized vs intact male). Waves of follicular activity were indicated by periodic increases in the number of follicles detected and an associated emergence of a dominant follicle that grew to greater than or equal to 7 mm. There was an inverse relationship (r = -0.2; P = 0.002) between the number of follicles detected and the diameter of the largest follicle. Successive dominant follicles emerged at intervals of 19.8 +/- 0.7 days in unmated and vasectomy-mated llamas and 14.8 +/- 0.6 days in pregnant llamas (P = 0.001). Lactation was associated with an interwave interval that was shortened by 2.5 +/- 0.05 days averaged over all groups (P = 0.03). Maximum diameter of anovulatory dominant follicles ranged from 9 to 16 mm and was greater (P less than 0.05) for non-pregnant llamas (anovulatory group, 12.1 +/- 0.4 mm; ovulatory group, 11.5 +/- 0.2 mm) than for pregnant llamas (9.7 +/- 0.2 mm). In addition, lactation was associated with smaller (P less than 0.05) maximum diameter of dominant follicles averaged over all reproductive statuses (10.4 +/- 0.2 vs 11.7 +/- 0.3 mm). The corpus luteum was maintained for a mean of 10 days after ovulation in non-pregnant llamas and to the end of the observational period in pregnant llamas. The presence (ovulatory non-pregnant group) and persistence (pregnant group) of a corpus luteum was associated with a depression in the number of follicles detected and reduced prominence of dominant follicles (anovulatory group greater than ovulatory non-pregnant group greater than pregnant group).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2250252 TI - Freeze-thaw-induced changes of the zona pellucida explains decreased rates of fertilization in frozen-thawed mouse oocytes. AB - Frozen-thawed oocytes have a reduced rate of fertilization (48.8%) when compared with unfrozen controls (97%). In this study we have used zona-drilling to bypass the zona pellucida and investigate whether the decreased rate of fertilization is due to freezing-induced changes in the zona pellucida which prevent sperm penetration. After zona drilling the fertilization rate of frozen-thawed oocytes (87.8%) was the same as for zona-intact unfrozen controls (88%), indicating that freeze-thaw-induced changes at the level of the zona pellucida were responsible for the decreased rate of fertilization. To determine whether the changes were occurring during the manipulations before and after freezing or the complete freeze-thaw cycle, oocytes were exposed to the complete set of manipulations normally experienced during cryopreservation and appropriate control groups. A small but significant decrease in the rate of fertilization (82.8%) was apparent in oocytes exposed to the manipulations before and after freezing compared with controls (92.2%). The freeze-thaw-induced changes in the zona pellucida therefore occur primarily during the complete freeze-thaw cycle itself and not the manipulations before and after freezing and are responsible for the decreased rate of fertilization observed in frozen-thawed oocytes. PMID- 2250253 TI - A role for short days in sustaining seasonal reproductive activity in the ewe. AB - This study tested the hypothesis that short days can prolong the breeding season of the ewe when reproductive activity is initiated by an endogenous process, as opposed to when it is driven by exposure to short days. Suffolk ewes were ovariectomized and treated with Silastic capsules containing oestradiol; reproductive activity was monitored from serum concentrations of LH. In this model, a rise in LH is indicative of onset of the breeding season and the duration of the elevation in LH is an indicator of length of reproductive activity. The ewes were subjected to 6-month alternations between long and short photoperiods such that the LH rise began during exposure to the inhibitory long photoperiod (i.e. it resulted from an endogenous process). When short days were provided soon after such a spontaneous onset of the LH rise, the duration of reproductive activity was greater than that observed when ewes were maintained in long days throughout the LH elevation (194 +/- 10 vs 155 +/- 15 days; P less than 0.02). Since the transition from anoestrus to the breeding season in Suffolk ewes maintained outdoors does not require a decrease in daylength and appears to be generated by an endogenous process, our results support the hypothesis that shortening photoperiod sustains the natural breeding season which begins in early autumn. PMID- 2250254 TI - Photoperiod and temperature interaction in the determination of reproduction of the edible snail, Helix pomatia. AB - Snails were kept in self-cleaning housing chambers in an artificially controlled environment. Mating was frequent under long days (18 h light) and rare under short days (8 h light) regardless of whether the snails were kept at 15 degrees C or 20 degrees C. An interaction between photoperiod and temperature was observed for egg laying. The number of eggs laid (45-50/snail) and the frequency of egg laying (90-130%) were greater in long than in short days (16-35/snail and 27-77%) but a temperature of 20 degrees C redressed, to some extent, the inhibitory effect of short days. At both temperatures only long photoperiods brought about cyclic reproduction over a period of 16 weeks, confirming the synchronizing role of photoperiod on the neuroendocrine control of egg laying in this species of snail. PMID- 2250255 TI - Embryo survival and conceptus growth after reciprocal embryo transfer between Chinese Meishan and Landrace x Large White gilts. AB - Embryos were transferred between Meishan and Landrace x Large White (control) gilts on Day 4 or 5 to establish approximately equal numbers of all four possible combinations of donor breed and recipient breed. The breed of the donor gilt significantly (P less than 0.01) affected embryo survival with 44.5% of transferred Meishan embryos and 69.6% of transferred control embryos surviving to Day 30 +/- 1. There was no influence of the breed of the recipient gilt on the proportion of embryos which survived. These differences in embryo survival between the two breeds could not be explained by differences in (1) the number of embryos transferred, (2) the stage of development of the embryos transferred, (3) the interval between ovulation and transfer or (4) the degree of asynchrony between donor and recipient gilt. On Day 30 +/- 1 embryos from control donors developed into longer fetuses (P less than 0.01) with larger allantoic sacs (P less than 0.05) than did embryos from Meishan donors. Fetuses in control recipients were longer (P less than 0.01), heavier (P less than 0.001) and had larger allantoic sacs (P less than 0.05) than fetuses occupying Meishan uteri. The interaction between breed of donor gilt and breed of recipient gilt did not significantly affect conceptus growth. These results suggest that Meishan pig embryos may be less tolerant to routine embryo transfer procedures than those of control gilts, that the genotype of the dam does not affect the proportion of embryos surviving to Day 30 +/- 1, and that both fetal and maternal factors affect conceptus growth. PMID- 2250256 TI - Effects of prolonged administration of anti-cumulus oophorus antibody on reproduction in mice. AB - Mice were passively immunized over 6 weeks with contraceptive doses of an anti cumulus oophorus antibody preparation. The persistence of oestrus, accompanied by complete inhibition of conception, was observed throughout treatment. After cessation of treatment, fertility was restored within 2 weeks. Histological examination did not reveal any depletion of the ovarian oocyte stock. These results warrant further research into the nature of cumulus antigens and their use in active immunization studies. PMID- 2250257 TI - Melatonin implants prevent the onset of seasonal quiescence and suppress the release of prolactin in response to a dopamine antagonist in the Bennett's wallaby (Macropus rufogriseus rufogriseus). AB - Three groups of adult female wallabies were maintained out of doors under conditions of natural photoperiod and temperature from late December to mid August. One group (M1; N = 6) received Silastic elastomer melatonin implants on 14 December, a second group (M2; N = 5) were given implants on 16 February and a third group (C; N = 7) were unimplanted controls. Group C animals had all ceased cycling by 15 March and the subsequent breeding season commenced on 5 July +/- 6.9 days. Group M1 wallabies continued to cycle throughout the experimental period and did not exhibit ovarian quiescence. In Group M2, 2/5 animals continued to undergo repeated oestrous cycles and 3/5 ceased cycling between 14 December and 27 January and began again after the insertion of melatonin implants on 16 February. The prolactin response 30 min after s.c. administration of the dopamine antagonist domperidone was determined approximately every 4 weeks. In Group C, peak responses were high during the period of seasonal quiescence (January-June; mean range 14.2-19.6 ng/ml) and fell significantly (P less than 0.02) at the beginning of the breeding season in early July to 7.4 +/- 3.1 ng/ml. In Group M1, prolactin levels remained low (2.8-8.2 ng/ml) throughout the course of the experiment while in Group M2, response to domperidone fell following the insertion of the implants and subsequently remained at levels similar to those in Group M1. Our data support the hypothesis that photoperiod-induced changes in the secretion of melatonin after the winter solstice drive this species into seasonal quiescence by influencing the dopaminergic control of prolactin secretion. PMID- 2250258 TI - Maintenance of the spinal nucleus of bulbocavernosus and perineal muscles in female Albino Swiss rats treated with perinatal dihydrotestosterone. AB - Female Albino Swiss rats were exposed to 5 alpha-dihydrotestosterone benzoate (DHTB) for the last 4 days of gestation, or for 4 days after birth, or both. Post natal DHTB exposure (as well as pre-plus post-natal exposure) resulted in a 2-3 fold increase in the number of motor neurones forming the spinal nucleus of bulbocavernosus (SNB); numbers were intermediate between those found in normal females (approximately 40) and males (approximately 200). These DHTB-treated groups also possessed perineal muscles which were approximately 25% of the weight of those in normal males. Transverse sections of one of the muscles (levator ani) showed that it had approximately half the muscle fibres of normal males. Females exposed prenatally to DHTB showed a small (but significant) rise in SNB numbers, but had no recognizable perineal muscles. PMID- 2250259 TI - Accident prevention. PMID- 2250260 TI - Sexual relationships between doctors and patients. PMID- 2250261 TI - A medical student's view of paediatrics. PMID- 2250262 TI - Slip-shod or safely shod: the bighorn sheep as a natural model for research. AB - Over a million injuries caused by slipping of footwear are believed to require treatment by doctors every year in the United Kingdom and many domestic animals are injured by slipping. Recent research has revealed that surface roughness of solings and floors is an important determinant of grip on lubricated surfaces and it is also known that soling friction is affected by hardness. The bighorn sheep (Ovis canadensis) an animal species which has adapted to a slippery environment, was studied to elucidate optimum roughness and hardness and other features which influence grip. Four adult ewes were examined in the London Zoo. The cloven hooves of this species are very mobile and the cranial tips of the hooves are the first parts to make contact with the ground. A very small contact area ensures penetration of a film of water. Mean roughness of the contact area was found to be 53 microns Rtm and the mean hardness 63 Shore A. These characteristics appear to facilitate an excellent grip on wet slippery rock but not on smooth ice. Further studies of the feet of wild species could contribute to an understanding of the factors which determine the safety of solings and floors. PMID- 2250263 TI - A study of scalds in Birmingham. AB - The causes of serious domestic scald injuries in Birmingham were studied for one year. Seventy-eight people sustained such scalds, 11 adults and 67 children. Only 51 of the patients received satisfactory first aid. Most accidents could have been avoided and the severity of the injury would have been less if appropriate first aid had been given. PMID- 2250264 TI - Survival in acute non-lymphocytic leukaemia following breast cancer. AB - Acute non-lymphocytic leukaemia (ANLL) occurs with increased frequency in women with previously diagnosed breast cancer. Adjuvant radiotherapy and chemotherapy are related to this increase. We studied the interrelationships among age at breast cancer diagnosis, interval to ANLL diagnosis, and survival in 54 women of whom 11 were from Kansas and 43 were from two other published series. Median age at breast cancer diagnosis was 50.5 years, median interval to ANLL diagnosis was 4.8 years, and median survival after ANLL diagnosis was 2.2 months. Increasing age was associated with a decrease of the interval to ANLL diagnosis just short of statistical significance (P = 0.0591). There was no association of survival with either age or the interval to ANLL diagnosis. With an increase in the use of adjuvant therapy in breast cancer there is a need to identify women at greatest risk of subsequently developing ANLL, at present not possible. PMID- 2250265 TI - Clinically and mammographically occult breast lesions demonstrated by ultrasound. AB - Histologic proof from 62 sites in 58 patients in whom an ultrasonic abnormality was detected in the absence of palpable or mammographic evidence revealed no malignancy. It is suggested that decision to biopsy be made on clinical grounds. PMID- 2250266 TI - Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis. AB - In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake. PMID- 2250267 TI - Continuing medical education at a university--evaluation of an MSc programme in general practice. AB - In 1986 London University launched a new MSc programme for GPs. This paper describes the problems met with, and the progress made by course members and tutors during the first part-time, 2-year course. We also describe some early measures of the outcome of this form of CME. PMID- 2250268 TI - Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions. AB - Old people are commonly receiving diuretics on admission to hospital. Diuretics are recognized as a risk factor for electrolyte disturbances; controversy exists about the relative risks of different combinations (in particular, co-amilozide [Moduretic]). We recorded the drug history and serum electrolytes in 1000 consecutive admissions to a geriatric hospital, and examined the relative prescribing rates of various diuretics in the community. Full results were obtained in 929 patients. A history of diuretic prescription was present in 353 (38%) of the patients; the mean serum sodium in this group (95% CI 136.0-137.1 mmol/l) was lower than in the 586 not prescribed diuretics (137.1-137.9 mmol/l). The difference was small but statistically significant (95% CI difference = 0.3 1.6 mmol/l; P less than 0.01). Hyponatraemia (serum sodium less than 130 mmol/l) was not significantly commoner in the 41 patients prescribed co-amilozide than in patients prescribed other diuretics. In general patients prescribed potassium retaining diuretics had a lower serum sodium than the others. There was a significant positive correlation between the serum potassium and the log [serum urea] (r = 0.26, P less than 0.001) and a weak negative correlation existed between sodium and potassium (r = -0.14; P less than 0.001). There was an association between the prescription of potassium-retaining diuretics and a higher serum potassium; also an association between the prescription of a loop or thiazide diuretic and a lower serum potassium. These interactions were shown by multiple regression analysis to be independent and additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250269 TI - A survey of the practice of regional anaesthesia. AB - A questionnaire designed to elucidate the popularity and practice of regional anaesthesia was circulated to all anaesthetists in the South East Thames Region. Two hundred and eleven completed questionnaires were received and subsequently analysed, a response rate of 65%. Regional anaesthesia was employed at least once per week by 83% of respondents usually in combination with general anaesthesia (77% of respondents). The provision of postoperative analgesia was cited as the main advantage by 86% of anaesthetists. PMID- 2250270 TI - Cardiopulmonary resuscitation: a panacea or an ethical decision? Discussion paper. PMID- 2250271 TI - On psychotherapist-patient sex: discussion paper. AB - The transference phenomenon as central to the problem of sex between psychotherapist and patient is discussed. Socio-semantic factors related to the evolution of psychotherapy from Freud to the present are presented. Contemporary pertinent studies are reported. Societal and legal attitudes towards offending therapists are briefly touched upon. Reflections are made and suggestions are offered for dealing with this serious issue. PMID- 2250272 TI - Making and taking health care decisions: discussion paper. PMID- 2250274 TI - Design and redesign of medical journals: a review. PMID- 2250275 TI - Medical advances consequent to the Great War 1914-1918. PMID- 2250273 TI - Epidemiology of mouth cancer in 1989: a review. AB - The oral cavity and pharynx combined is the sixth commonest site of cancer in both sexes. In many countries the mortality rate is increasing among younger men born since approximately 1910-1920. A causal role in the aetiology of mouth cancer has been established for tobacco use, both smoking and chewing, separately and in conjunction with betel-quid chewing; with alcohol consumption and, less certainly, with other factors such as poor oral hygiene, nutritional factors and certain occupational exposures. In Western countries, there is convincing evidence that a large attributable risk can be ascribed to the joint habits of cigarette smoking and alcohol consumption. In Asian societies, a high attributable risk can be ascribed to cigarette smoking and betel chewing. Mouth cancer is at the same time an important form of cancer, and one for which practical prospects for prevention already exist. Against this background of a continually increasing trend among younger persons, it seems essential to engage upon programmes of prevention, including increasing awareness for early detection, against mouth cancer at the present time. PMID- 2250276 TI - Alpha-1-antitrypsin deficiency panniculitis. PMID- 2250277 TI - Delayed presentation of rectal perforation. PMID- 2250278 TI - Oesophago-atrial fistula: a side effect of tetracycline? PMID- 2250279 TI - Primary carcinoma of the cystic duct causing obstructive jaundice. PMID- 2250280 TI - Hepatic hydrothorax without ascites: a rare form of a common complication. PMID- 2250281 TI - Rare type of visceral myopathy mimicking anorexia nervosa. PMID- 2250282 TI - Relationship between longevity and lifeline. PMID- 2250283 TI - The art of resuscitation. PMID- 2250284 TI - Lancefield group F and related streptococci. PMID- 2250285 TI - Interactions of Escherichia coli and Proteus mirabilis with mouse mononuclear phagocytes. AB - Five strains of enterobacteria (three of Escherichia coli and two of Proteus mirabilis) were studied to assess and compare their phagocytic uptake and intracellular killing by mouse macrophages. Each strain was injected intraperitoneally into separate groups of mice and peritoneal exudate cells were harvested after 3 min for phagocytosis to occur in vivo. Acridine orange staining showed that there were approximately 10-fold fewer intracellular P. mirabilis than E. coli cells. The average numbers of viable intracellular bacteria per leucocyte were 0.03 and 0.02 for P. mirabilis strains M13 and H1, respectively, and 0.48, 0.45, and 0.28 for E. coli strains M14, A-D M5 and H40. Thus, both P. mirabilis strains were ingested less readily than any of the three E. coli strains (p less than 0.01). The rates of in-vitro intracellular killing were similar for all five strains of bacteria. The intracellular killing constants (Kk) for the three mouse isolates were 0.017, 0.016 and 0.020 min for E. coli M14 and A-D M5, and P. mirabilis M13, respectively; the Kks for the two human isolates were 0.026 and 0.029/min for E. coli H40 and P. mirabilis H1, respectively. The Kks for all five strains were not significantly different. Assuming that the numbers of viable intracellular bacteria at the beginning of the assay represented 100% viability, 6-17% of the intracellular bacteria remained viable after 2 h, reflecting log10 3.9-5.6 bacteria (6-8) x 10(6) peritoneal exudate cells. Intravenous injection of these five strains into separate groups of mice demonstrated that the P. mirabilis strains were more virulent than the E. coli strains. Injection of each P. mirabilis strain was associated with ruffled fur and death, whereas mice given any of the three E. coli strains remained visibly healthy and none died. Consistent with these observations, quantitation of viable bacteria in the liver and spleen showed that greater numbers of P. mirabilis M13 than of E. coli M14 or A-D M5 persisted in these organs; similarly greater numbers of P. mirabilis H1 than of E. coli H40 persisted in the liver and spleen. Because the rates of intracellular killing of these five strains were similar, the relative virulence of both strains of P. mirabilis appeared to be associated with decreased phagocytic uptake rather than differences in intracellular survival. PMID- 2250286 TI - Functional similarity between the haemolysins of Escherichia coli and Morganella morganii. AB - Haemolysin produced by a clinical isolate of Morganella morganii was examined for antigenic relatedness to the haemolysin of Escherichia coli and for similarities in mode of action. The M. morganii haemolysin migrated in SDS-PAGE as a single protein band with a slightly higher molecular weight than that of E. coli haemolysin. Several murine monoclonal antibodies against E. coli haemolysin cross reacted with the M. morganii haemolysin in Western blots. Diminished haemolysis in the presence of osmotically-stabilising solutes indicated the formation of a pore by M. morganii haemolysin with an effective diameter of 1.5-3 nm. Results from dose-response experiments indicated that a single "hit" was sufficient for lysis of an erythrocyte. Detergent solubilisation of toxin-treated membranes led to recovery of bound toxin exclusively in monomeric form. M. morganii haemolysin was a potent leucocidin, that caused rapid leakage of ATP and death of human polymorphonuclear leucocytes. Under in-vitro conditions M. morganii haemolysin displayed similar leucocidal and haemolytic efficiency. The data demonstrate that M. morganii haemolysin shows functional properties virtually identical with those of E. coli haemolysin. PMID- 2250287 TI - Hepatotoxic activity of Campylobacter jejuni. AB - Hepatotoxic factor(s) were isolated from whole-cell lysates of Campylobacter jejuni GIFU 8734 and purified by chromatography. A single intravenous injection of 10 micrograms of this factor reproducibly produced hepatitis in mice, as determined by histology and liver function tests. The hepatic lesions were very similar to those evoked by C. jejuni infection. Tissue-culture studies with mouse hepatocytes demonstrated that low concentrations of the factor caused release of hepatic enzymes into the medium without appreciable cytolysis. High concentrations of the factor induced cytolysis. These effects were neutralised by antiserum to the factor, but not by antisera to the lipopolysaccharide of C. jejuni or to the heat-labile enterotoxin of Escherichia coli. Among 20 clinical isolates of C. jejuni, only four evoked hepatitis in mice and produced the hepatotoxic factor. PMID- 2250288 TI - Identification of Fusobacterium species by the electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate reductase in relation to their DNA base composition and peptidoglycan dibasic amino acids. AB - Rapid identification of Fusobacterium spp. is hampered by their inability to ferment carbohydrates and the availability of relatively few useful phenotypic characters. In an attempt to identify new diagnostic markers for species, we reported recently the potential utility of glutamate dehydrogenase (GDH) electrophoretic mobilities for distinguishing eight species of Fusobacterium. We have extended these observations to include all recognised members of the genus except F. prausnitzii and F. perfoetens, and our results show that they cluster into three broad electrophoretic groups. Some species, such as F. periodonticum, F. simiae and F. necrophorum, possessed GDH with similar electrophoretic mobilities. However, within such clusters, the electrophoretic migration of 2 oxoglutarate reductase (OGR) distinguished between species. Neither GDH or OGR mobility alone clearly differentiated all species, but their combined use provided unambiguous discrimination of all species except F. varium and F. mortiferum. The DNA base compositions of all species except F. naviforme (ATCC 25832) and F. sulci, were within the range 26-34 mol% G + C, suggesting the genus may be homogeneous. However, the peptidoglycan composition divided the genus into two major groups that contained either lanthionine or diaminopimelic acid; F. mortiferum peptidoglycan contained both dibasic amino acids. PMID- 2250289 TI - A rat model of Staphylococcus aureus chronic osteomyelitis that provides a suitable system for studying the human infection. AB - Chronic osteomyelitis was produced by inoculating Staphylococcus aureus into rat tibia. The infection was characterised grossly by bone deformation and histopathologically by inflammation and the presence of coccal organisms sequestered within the bone tissue. Further observations by scanning electronmicroscopy demonstrated bacteria in microcolonies surrounded by dehydrated amorphous material that was considered to be glycocalyx. Transmission electronmicroscopy, when aided by antibody stabilisation, revealed extensive glycocalyx production within the tibia. These findings indicate that the rat model of chronic S. aureus osteomyelitis mimics the human infection with respect to the sessile mode of growth of bacteria within the bone. Serum antibody levels were assayed by ELISA and immunoblotting procedures. After an initial increase, ELISA titres remained relatively stable, apparently indicating the establishment of chronic osteomyelitis, whereas in immunoblotting an increase in titre over the course of infection was observed. Whole-cell ELISA revealed less subtle differences in antibody titre than did immunoblotting with cell-wall antigen. We found that mid-range antigens, including an antigen implicated as protein A, featured prominently in the immune response in this model of infection. PMID- 2250290 TI - Vaccination of mice with lipopolysaccharide (LPS) and LPS-derived immuno conjugates from Leptospira interrogans. AB - Mice were vaccinated with lipopolysaccharide (LPS) from Leptospira interrogans serovar pomona or hardjo, or with the polysaccharide (PS) fraction of the LPS, or with an immunoconjugate of PS and diphtheria toxoid (DT). Maximum agglutinin titres were found 6-10 weeks after vaccination with LPS or PS-DT conjugate; the latter elicited antibody titres at least 10 times higher than those produced in response to LPS. Animals failed to react significantly to PS. Titres elicited by antigens of serovar pomona were higher than those elicited by serovar hardjo. PMID- 2250292 TI - Cigarette smoking and hematopoietic cancer. PMID- 2250291 TI - Extrachromosomal DNA in human cancers. PMID- 2250293 TI - Cancer vaccines: researchers seek to turn promise into practice. PMID- 2250294 TI - Good news for former smokers from Surgeon General Novello. PMID- 2250295 TI - The national economic burden of cancer: an update. PMID- 2250296 TI - Ability of circular extrachromosomal DNA molecules to carry amplified MYCN proto oncogenes in human neuroblastomas in vivo. AB - Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification. PMID- 2250297 TI - Monoclonal antibodies to immunogenic lymphoma cell variants displaying impaired neoplastic properties: characterization and applications. AB - Immunogenic, nontumorigenic cell variants derived from the highly tumorigenic mouse lymphoma cell line S-49 were used to raise monoclonal antibodies (MAbs) in syngeneic BALB/c mice. MAbs of the following specifications were derived: (a) MAbs that interacted preferentially with the immunogenic variants, (b) MAbs that interacted with both immunogenic variants and parental tumorigenic cells, and (c) a MAb that interacted with both immunogenic and tumorigenic S-49 cells and the normal BALB/c splenocytes. Six MAbs raised in this way were found to recognize at least five different cell-surface epitopes. Functional analysis of the different MAbs suggested their potential usefulness in passive immunization against parental tumorigenic cells as well as in enrichment of immunogenic cells from a mixed population containing a preponderance of tumorigenic cells. PMID- 2250298 TI - Carcinogen hemoglobin adducts, urinary mutagenicity, and metabolic phenotype in active and passive cigarette smokers. AB - In 100 healthy volunteers, we have studied the relationship between the type (air or flue-cured) and number of cigarettes smoked and different biomarkers relevant to the risk of bladder cancer, including the levels of 4-aminobiphenyl (ABP) hemoglobin adduct (a marker of internal dose), urinary mutagenicity in Salmonella typhimurium TA98, and the N-acetylation phenotype (a marker of susceptibility). ABP is a potent bladder carcinogen that is N-acetylated as an overall detoxification step. Levels of the ABP hemoglobin adduct were higher in smokers of black tobacco (air-cured) than in smokers of blond tobacco (flue-cured), confirming our earlier study. In addition, "slow" acetylators had higher levels of the ABP hemoglobin adduct for the same type and quantity of cigarettes smoked. Urinary mutagenicity was also associated with quantity of cigarettes but not with the acetylation phenotype. Convex dose-response relationships were found between the amount smoked and ABP hemoglobin adduct levels or urinary mutagenicity. In 15 nonsmokers who reported exposure to environmental tobacco smoke, ABP hemoglobin adduct levels, unlike urinary mutagenicity, were found to be an aspecific exposure indicator. PMID- 2250299 TI - History of cigarette smoking and risk of leukemia and myeloma: results from the Adventist health study. AB - The risks of leukemia and myeloma associated with cigarette smoking were evaluated in a cohort study of 34,000 Seventh-day Adventists. Although Seventh day Adventists do not smoke by church proscription, many are adult converts who smoked cigarettes prior to their baptism into the church. In comparison with those who never smoked, ex-smokers experience a relative risk of 2.00 (95% confidence interval = 1.01-3.95) for leukemia and 3.01 (95% confidence interval = 1.13-8.05) for myeloma. Risks increased in a dose-response fashion with increasing numbers of cigarettes smoked daily for both leukemia (trend P = .009) and myeloma (trend P = .005). Also, the risks of both leukemia and myeloma increased with the total duration of cigarette smoking. The cigarette smoking leukemia relationship was strongest for myeloid leukemia, for which ex-smokers experienced a relative risk of 2.24 (95% confidence interval = 0.91-5.53). These data lend support to the hypothesis that cigarette smoke may induce malignant degeneration in bone marrow and its products. PMID- 2250300 TI - Schedule dependence for cisplatin and etoposide multifraction treatments of spheroids. AB - Cisplatin and etoposide are both widely used as antineoplastic chemotherapeutic agents. Two approaches are generally adopted when an attempt is made to maximize the efficiency of these drugs: concurrent use (where synergism is expected) or sequential administrations (exploiting the antiproliferative effects of etoposide). To differentiate between these approaches in a quantitative manner, we exposed an in vitro tumor model (V79 multicell spheroids) to the drugs, using treatment regimens with a constant weekly dose intensity. Some treatment schedules suggested the development of drug resistance, but this resulted from a changing growth fraction in the spheroids rather than from selection for or induction of cellular resistance. Fewer administrations of larger doses were generally less satisfactory than multiple, smaller treatments. The most effective sequence was an alternating regimen, by which the cytoreductive effects of cisplatin resulted in recruitment of quiescent cells into active proliferation, enhancing in turn the efficiency of subsequent etoposide treatment. PMID- 2250301 TI - Sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. The Uppsala-Orebro Breast Cancer Study Group. PMID- 2250302 TI - Models that predict the risk of developing breast cancer. PMID- 2250303 TI - Production of matrix-degrading enzymes determined by tumor implantation site. PMID- 2250305 TI - Stanford indirect-cost investigations weigh heavy on university research. PMID- 2250306 TI - The 1971 National Cancer Act--did it pay off? PMID- 2250304 TI - Evaluating cancer chemotherapy by infusion. PMID- 2250307 TI - NCI reauthorization decisions postponed. PMID- 2250308 TI - Clinical alerts: Broder discusses pros and cons on the record. PMID- 2250309 TI - Human gene therapy trial in cancer patients about to begin. PMID- 2250310 TI - Structure, function, and clinical significance of human tumor antigens. PMID- 2250311 TI - Mechanism of antitumor activity of tumor necrosis factor alpha with hyperthermia in a tumor necrosis factor alpha-resistant tumor. AB - Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis. PMID- 2250312 TI - Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. AB - Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation. PMID- 2250313 TI - Lipolytic factors associated with murine and human cancer cachexia. AB - We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells. PMID- 2250314 TI - Effects of the differentiating agent hexamethylene bisacetamide on normal and myelodysplastic hematopoietic progenitors. AB - Hexamethylene bisacetamide (HMBA; NSC 95580) is a potent polar-planar differentiating agent of leukemia and solid tumor cell lines in vitro at clinically achievable concentrations. HMBA is currently being studied in patients with myelodysplastic syndrome. Previous phase I trials have demonstrated that HMBA produces hematologic toxicity in morphologically normal bone marrows of patients with solid tumors. Because of concern that HMBA may produce more severe myelotoxicity in patients with myelodysplastic syndrome since these patients have limited hematopoietic reserves, we studied the effects of HMBA on myelodysplastic and normal hematopoietic progenitors in vitro. HMBA concentrations that are optimal for differentiation in vitro (2 to 5 mmol/L) and HMBA concentrations that are being achieved in clinical trials (1 to 2 mmol/L) inhibited the growth of granulocyte-macrophage colony-forming units and erythroid burst-forming units from all 15 patients with myelodysplastic syndrome and all 4 normal subjects, HMBA did not induce proliferation of myelodysplastic or normal progenitors at any concentration; rather, it produced nearly identical inhibition of normal and myelodysplastic hematopoietic progenitors. HMBA also produced quantitatively similar inhibition of clonogenic leukemic growth of two myeloid leukemia cell lines. For a differentiating agent to be effective, it will likely have to either produce both differentiation and proliferation of abnormal hematopoietic progenitors or show selective inhibitory effects on abnormal as compared with normal progenitors. Although the mechanisms responsible for the antiproliferative effects of HMBA cannot be determined from this study, similar inhibitory effects of HMBA on normal and abnormal hematopoietic progenitors suggest that HMBA may be of limited utility in producing and sustaining elevations of peripheral blood cell counts in patients with myelodysplastic syndrome. PMID- 2250315 TI - High-dose cisplatin and dacarbazine in the treatment of metastatic melanoma. PMID- 2250316 TI - Increased risk of breast cancer in women with central obesity: additional considerations. PMID- 2250317 TI - Interaction of the tick (Haemaphysalis leporispalustris) with a cyclic snowshoe hare (Lepus americanus) population. AB - Prevalence and intensity of the tick, Haemaphysalis leporispalustris, were monitored during 1963 to 1976 in a cyclic snowshoe hare (Lepus americanus) population near Rochester, Alberta, Canada. Prevalence was near zero from December through March, and near 100% among adult hares from May through September. Prevalence among juvenile hares approached 100% by age 2 mo. Intensity peaked for both adults and juveniles during May-June and again in August. Mean intensities were significantly higher among adult males than adult females in 5 of 13 yr, and almost significant in two others. Tick intensities were lowest during 3 yr, 1969 to 1971, when hare densities were highest. Tick intensities in spring were correlated with intensities the previous fall. Survival of marked adult and juvenile hares was unrelated to intensities of infestation. Mean numbers of corpora lutea and embryos tended to be lower among adult females with heavy tick infestations, and intra-uterine losses rose steadily from about 3 to 13% as tick intensities increased from none to heavy. Comparison of average tick intensities on adults 1-, 2-, and greater than or equal to 3-yr-old yielded no evidence of increased immunity with age. PMID- 2250318 TI - Effects of host and spatial factors on a haemoproteid community in mourning doves from western Texas. AB - Two species of hematozoa, Haemoproteus columbae and H. sacharovi, were observed on thin blood smears from populations of mourning doves (Zenaida macroura) in the Rolling Plains (RP, a semiarid dryland farming and grazing area) and Southern High Plains (SHP, an intensively cultivated and irrigated agricultural region with playa lakes) of western Texas (USA). Prevalences of H. columbae and H. sacharovi were 91 and 18% in doves from the RP (n = 44 doves examined) and 81 and 36% in those from thte SHP (n = 84), respectively. Although the prevalences of these species were not significantly different between the RP and SHP, the prevalence of H. sacharovi was significantly greater in juvenile versus adult doves from both localities. Mixed infections of both haemoproteid species occurred in 11 and 24% of the doves from the RP and SHP, respectively. The frequency distributions of the relative density values (numbers of parasites/2,000 erythrocytes counted) of H. columbae and H. sacharovi were overdispersed in hosts from both localities. Relative densities of H. columbae were significantly higher in mourning doves from the RP versus the SHP; likewise those of H. sacharovi were significantly greater in juvenile versus adult doves and between localities. Observed differences in prevalence and relative density of the two species in the haemoproteid community across spatial and host variables may reflect differences in vector transmission and in the physiological and immunological status of the host. This study emphasizes the importance of using adequately quantified density data versus only prevalence data when examining microparasite communities at the component community level. PMID- 2250319 TI - Occurrence and seasonal transmission of hematozoa in wild turkeys. AB - The occurrence and seasonal patterns of transmission of the blood protozoa of wild turkeys (Meleagris gallopavo silvestris) were studied at Tallahala Wildlife Management Area (TWMA) (Jasper County, Mississippi, USA). Blood smears obtained from wild turkeys in winter, spring and summer, and from sentinel domestic turkeys throughout the year were examined for Haemoproteus meleagridis and Leucocytozoon smithi. Whole blood from wild turkeys captured in summer was subinoculated into malaria-free domestic turkey poults and recipient birds were examined for Plasmodium spp. The prevalence of H. meleagridis and L. smithi were not different (P greater than 0.05) between adults and juveniles or between male and female turkeys in any season. Leucocytozoon smithi was not detected in poults in summer or in juveniles examined in winter. Sentinel studies and information from wild birds revealed that transmission of H. meleagridis and L. smithi did not overlap. Haemoproteus meleagridis was transmitted from May through November, while L. smithi was transmitted only from January through April. The onset of transmission of H. meleagridis coincided with peak hatching (mid-May) and brood rearing (May-November) of turkey poults. Plasmodium spp. were not found in turkeys from TWMA (n = 27) nor in birds from three widely separated counties (n = 28) in Mississippi. PMID- 2250320 TI - Helminth parasitism in martens (Martes americana) and ermines (Mustela erminea) from Washington, with comments on the distribution of Trichinella spiralis. AB - Helminths are reported for the first time from ermines (Mustela erminea) and martens (Martes americana) in Washington (USA). Among 22 adult ermines, 41% were infected by one or more of five species (Taenia mustelae, Alaria mustelae, Molineus patens, M. mustelae and Trichinella spiralis). Among 78 adult martens from three geographic localities, the prevalence was 83%. Nine species were identified (Mesocestoides sp., T. mustelae and T. martis americana, Euryhelmis squamula, M. patens, Baylisascaris devosi, Physaloptera sp., Soboliphyme baturini and T. spiralis). Trichinella spiralis occurred with a maximum prevalence of 50% in martens, but only occurred in 9% of ermines. Compression and digestion techniques provided a similar estimate of prevalence of T. spiralis, yet neither was entirely accurate in identifying all infected hosts. The species richness of the helminth community of martens in Washington was greater than that reported from other regions of North America. PMID- 2250321 TI - Survey of hepatic and pulmonary helminths of wild cervids in Alberta, Canada. AB - During the 1988 hunting season, livers and lungs from 263 mule deer (Odocoileus hemionus hemionus), 198 moose (Alces alces), 147 white-tailed deer (Odocoileus virginianus), and 94 wapiti (Cervus elaphus nelsoni) from Alberta (Canada) were collected for parasitological examination. Most of the samples (89%) were submitted by big game hunters throughout the province. Giant liver fluke (Fascioloides magna) was found in 9% of 22 yearling and 29% of 65 adult wapiti; 4% of 161 adult moose; and 2% of 97 adult white-tailed deer. The intensity of infection generally was low; however, one wapiti had over 600 flukes in the liver. Infections were restricted to alpine and montane regions in southwestern Alberta (97%) as well as boreal uplands of the Cypress Hills in southeastern Alberta (3%). Other parasites recorded included Taenia hydatigena cysts in liver of 61% of 191 moose and 14% of 247 mule deer. Dictyocaulus viviparus was found in lungs of 14% of 50 moose, 14% of 118 mule deer, 12% of 41 wapiti, and 6% of 54 white-tailed deer. Echinococcus granulosus cysts were found in lungs (and occasionally liver) of 37% of 51 moose. Incidental infections of Thysanosoma actinoides, Orthostrongylus macrotis, and Taenia omissa were recorded. Adult Dicrocoelium dendriticum were collected from liver of two wapiti, one mule deer, and one white-tailed deer from the Cypress Hills. PMID- 2250322 TI - Epidemiologic features of an intracranial abscessation/suppurative meningoencephalitis complex in white-tailed deer. AB - Case records of 683 white-tailed deer (Odocoileus virginianus) submitted to the Southeastern Cooperative Wildlife Disease Study (Georgia, USA) for diagnostic purposes from 1971 to 1989 were reviewed for the occurrence of pyogenic infections of the central nervous system, specifically intracranial abscessation or suppurative meningoencephalitis. These conditions, either alone or in combination, were diagnosed in 24 of 683 (4%) deer. Thirteen genera of bacteria were isolated; the most frequent species was Actinomyces pyogenes. The disease was strongly sex biased (P less than 0.01); 88% of the cases occurred in males. Cases were more prevalent (P less than 0.05) in older bucks; the median age of infected bucks was 3.2 yr, and 71% of these were greater than or equal to 2.5-yr old. Intracranial abscessation/suppurative meningoencephalitis cases accounted for 20% of the diagnoses among 56 bucks greater than or equal to 3-yr-old. Cases were seasonal, occurring only from October to April. Characteristic necrosis, erosion, and pitting of skull bones were common, and this bone damage may be useful in determining cause of death when only skeletal remains are found. Males, especially older bucks, apparently are predisposed to intracranial abscessation/suppurative meningoencephalitis because of the cycle of antler development and behavioral traits associated with reproduction. The strong bias toward prime age bucks suggests that these infections could specifically hinder management strategies designed to produce populations with older buck age structures. PMID- 2250323 TI - A survey of infectious diseases in wild turkeys (Meleagridis gallopavo silvestris) from Arkansas. AB - Wild turkeys (Meleagridis gallopavo silvestris) trapped as part of a relocation program by the Arkansas Game and Fish Commission were tested for selected infectious diseases and parasites. The 45 birds were trapped at four locations in Pope, Scott, and Montgomery counties (Arkansas, USA). Forty-four blood samples for serology, 27 blood smears and 12 fecal samples were collected. Of the serum samples tested, 20 of 44 (45%) were positive for Pasteurella multocida by enzyme linked immunosorbent assay (ELISA), 42 of 44 (95%) were positive for Bordetella avium by ELISA, and 15 of 44 (34%) were positive for Newcastle disease virus antibody by the hemagglutination inhibition test. All serum samples were negative for Mycoplasma gallisepticum, Mycoplasma synoviae, avian paramyxovirus 3, avian influenza, hemorrhagic enteritis, Marek's disease, avian encephalomyelitis, laryngotracheitis, Salmonella pullorum and Salmonella gallinarum. Haemoproteus meleagridis was found in eight of 27 (30%) and Leucocytozoon smithi in nine of 27 (33%) blood smears; all smears were negative for Plasmodium hermani. Enteric parasites included Ascaridia dissimilis, Heterakis gallinarum, Eimeria dispersa and Raillietina spp. This study was an attempt to document the health status and disease exposure of wild turkeys in Arkansas to aid in managing and preventing the spread of disease agents to wild turkeys and other species of birds. PMID- 2250324 TI - Surveillance and epidemiologic mapping of monoclonal antibody-defined rabies variants in Florida. AB - Brain tissues from 128 rabid animals from Florida in 1987 and 1988 were analyzed with monoclonal antibodies and cases were mapped by species and antigenic variant. The single variant found in terrestrial animals was distinguished easily from the variety of antigenic variants identified for infected bats, and there was no evidence of transmission of rabies between bats and terrestrial animals. The raccoon (Procyon lotor) appeared to be the sole maintenance source for terrestrial animal rabies in Florida. PMID- 2250325 TI - Wild carnivore acceptance of baits for delivery of liquid rabies vaccine. AB - A series of experiments are described on the acceptance, by red foxes (Vulpes vulpes) and other species, of two types of vaccine-baits intended to deliver liquid rabies vaccine. The baits consisted of a cube of sponge coated in a mixture of tallow and wax, or a plastic blister-pack embedded in tallow. All baits contained tetracycline as a biological marking agent: examination of thin sections of carnivore canines under an ultraviolet microscope revealed a fluorescent line of tetracycline if an individual had eaten baits. Baits were dropped from fixed-wing aircraft flying about 100 m above ground at approximately 130 km/h. Flight lines followed the edges of woodlots midway between parallel roads. Baits were dropped at one/sec, resulting in one bait/36 m on the ground, or 17 to 25 baits per km2. Crows (Corvus brachyrhynchos) removed many baits, but did not appear to lower the percent of the fox population which took bait. Dropping baits only into corn and woodland to conceal baits, to reduce depredation by crows, reduced acceptance by foxes. Acceptance by foxes ranged between 37 and 68%. Meat added as an attractant did not raise acceptance. Presence, absence, color and perforations of plastic bags did not alter bait acceptance. Dispersal by juvenile foxes probably lowered the estimates of bait acceptance. It took 7 to 17 days for 80% (n = 330) of foxes to eat their first bait. The rapidity with which foxes picked up their first bait appeared more affected by unknown characteristics of years or study areas than by experimental variables. Skunks (Mephitis mephitis) and raccoons (Procyon lotor) also ate these baits, but acceptance was lower. Small mammals contacted baits, but rarely contacted the vaccine, which had the potential for vaccine-induced rabies in some species. Aerial distribution of baits was more cost-effective than ground distribution as practiced in Europe. This system has potential for field control of rabies, although higher acceptance will be desirable. PMID- 2250326 TI - The C120 Magnum with pan trigger: a humane trap for mink (Mustela vison). AB - The C120 Magnum trap, equipped with a 66 x 69 mm pan trigger, which favored double strikes in the neck and thorax regions, successfully killed nine of nine wild mink (Mustela vison) in simulated natural conditions. Average times to loss of consciousness and heartbeat were estimated at less than 72 (+/- 24) sec and 158 (+/- 48) sec, respectively, after firing of the trap. This study confirmed that the C120 Magnum trap can be expected to render greater than 79% of all captured mink unconscious in less than or equal to 3 min (P less than 0.05). This is the first mink kill trap to meet the requisites of the Canadian General Standards Board regarding killing traps. PMID- 2250327 TI - Serologic survey for Actinobacillus capsulatus in free-ranging snowshoe hares (Lepus americanus) from Alaska and Alberta. AB - A plate agglutination method was developed to test sera from free-ranging snowshoe hares (Lepus americanus) captured in Alaska (USA) or Alberta (Canada) for antibody against Actinobacillus capsulatus. Antiserum against A. capsulatus was prepared in a domestic rabbit. A concentrated suspension of formalin-killed A. capsulatus was prepared for use as an antigen. Serum antibody prevalence for hares was 98 of 239 (41%) in Alaska and 51 of 111 (46%) in Alberta. Prevalence in Alaska peaked in 1981 corresponding to a peak in hare population density. Seasonal prevalence peaked in May in Alaska. Prevalence at one capture site in Alaska was significantly higher than at four other sites. There was no difference in sex-specific prevalence for either Alaska or Alberta. PMID- 2250329 TI - Aberrant migration by Toxocara pteropodis in flying-foxes--two case reports. AB - Adults of the large nematode, Toxocara pteropodis, have not previously been reported from extra-intestinal sites in their hosts, juvenile flying-foxes (fruit bats of the genus Pteropus). In one captive bat which died unexpectedly, a nematode was found coiled within the gall bladder and common bile duct; in another a nematode was in the esophagus and protruded into the laryngopharynx. Like other ascaridoids, this species is capable of aberrant migration. PMID- 2250328 TI - Nematode related spinal myelomeningitis and posterior ataxia in muskoxen (Ovibos moschatus). AB - In the fall of 1988 all five animals in a herd of muskoxen (Ovibos moschatus) developed clinical signs of posterior ataxia. Postmortem investigation revealed inflammatory lesions of the caudal part of the spinal cord, mainly as leptomeningitis. Nematodes were seen in close association with the lesions. Although not identified, the parasites were probably an Elaphostrongylus sp. PMID- 2250330 TI - Parelaphostrongylus andersoni (Nematoda: Protostrongylidae) in white-tailed deer from Michigan. AB - Dorsal-spined larvae in fecal samples from free-ranging white-tailed deer (Odocoileus virginianus) in Michigan and Pennsylvania were used as a source of larvae to infect a hand-raised white-tailed deer fawn. The fawn receive 200 third stage larvae and passed dorsal-spined larvae in feces 66 days later. Muscleworm (Parelaphostrongylus andersoni), and meningeal worm (Parelaphostrongylus tenuis) were recovered at necropsy. Two white-tailed deer and seven wapiti (Cervus elaphus) exposed to larvae of the source from Pennsylvania harbored only P. tenuis. This is the first report of P. andersoni in the midwestern United States and extends the known range of this muscleworm in free-ranging white-tailed deer. Concurrent infections of P. andersoni and P. tenuis have not been established previously in experimentally infected fawns. PMID- 2250331 TI - Dioctophymosis in the little grison (Galictis cuja). AB - Two cases of dioctophymosis in wild little grisons (Galictis cuja) were found in Parana State (southern Brazil). One female host was infected with eight nematodes and a male harbored a single parasite. This represents the first report of the giant kidney nematode (Dioctophyme renale) in the little grison. PMID- 2250332 TI - Occurrence of tetrathyridia of Mesocestoides sp. (Cestoidea: Cyclophyllidea) in North American anurans (Amphibia). AB - A new host and geographic locality record is reported for tetrathyridia of Mesocestoides sp. in two species of ranid frogs (Rana berlandieri and R. pipiens) from Texas and New York, respectively. Tetrathyridia were found encapsulated in liver and mesenteries of the hosts. Morphological examination and experimental inoculation of these tetrathyridia into mice demonstrated the absence of capacity for asexual proliferation. Overall prevalence of infection was low in anurans from Arkansas, Texas and New York, but intensities can be generally high. In addition, a summary of frogs and toads from North America reported as hosts of tetrathyridia of Mesocestoides sp. is presented. PMID- 2250333 TI - Helminth parasites of unisexual and bisexual whiptail lizards (Teiidae) in North America. III. The Chihuahuan spotted whiptail (Cnemidophorus exsanguis). AB - Twenty-four of 87 (28%) parthenogenetic Chihuahuan spotted whiptails (Cnemidophorus exsanguis) from nine counties of New Mexico and seven counties of Texas were infected with one or more endoparasites. These included a linstowiid cestode (Oochoristica bivitellobata) in seven (8%), a larval spirurid nematode (Physaloptera sp.) in nine (10%) and an oxyurid nematode (Pharyngodon warneri) in 10 (11%). This note, the third in a series of reports on helminths of Cnemidophorus spp., documents parasites in C. exsanguis for the first time. PMID- 2250334 TI - A coprological survey of parasites of wild mantled howling monkeys, Alouatta palliata palliata. AB - Fecal samples from 155 mantled howling monkeys (Alouatta palliata palliata) examined at Centro Ecologico La Pacifica, Guanacaste Province, Costa Rica, revealed 75 (48%) had parasitic infections. A sampling of nine howling monkeys from Santa Rosa National Park. Costa Rica indicated only one infected animal (11%). Only three of 19 (16%) spider monkeys (Ateles geoffroyi) also from Santa Rosa were infected. Controrchis biliophilus, Trypanoxyuris minutus, unidentified strongylid eggs and Isospora sp. oocysts were found. Three monkeys from La Pacifica died and were examined for adult helminths. They were infected with Ascaris lumbricoides, C. biliophilus and T. minutus. PMID- 2250335 TI - Geographic occurrence of Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) infesting white-tailed deer in North Carolina. AB - A state-wide survey to determine the occurrence and comparative numbers of ticks infecting white-tailed deer (Odocoileus virginianus) was conducted in North Carolina (USA). One thousand six hundred twenty nine deer were examined in 60 of 100 counties; with the exception of one county in the piedmont region, all tick infested deer occurred in the coastal plain. Ixodes scapularis (46%) and Amblyomma americanum (53%) were the most prevalent species encountered and accounted for more than 98% of the 4,286 ticks collected. Some specimens of Dermacentor albipictus and Amblyomma maculatum also were collected. PMID- 2250336 TI - Psoroptic scabies in Rocky Mountain bighorn sheep (Ovis canadensis canadensis) from Wyoming. AB - Thirteen Rocky Mountain bighorn sheep (Ovis canadensis canadensis) with clinical signs of psoroptic scabies were captured in Wyoming. Signs included droopy ears, depilation on the head and neck, and exudate in the ears. Mites were identified as either Psoroptes cervinus or P. equi. Two ewes with scabies at the time of original capture had no clinical signs of mite infection 1 and 2 yr later. PMID- 2250337 TI - Gill sphaerosporosis in goldfish (Carassius auratus). AB - Infections caused by a Sphaerospora sp. resembling S. chinensis are reported for the first time in goldfish (Carassius auratus) from North America. The myxosporean was found in the respiratory epithelium of the gill of pond-reared fish. Spores from stained tissue sections were spherical with an equal mean length and width of 6.3 microns. Spore valves were thickened at the suture which lies in a plane perpendicular to two prominent pyriform polar capsules. The polar capsules were 4.0 x 2.8 microns in length and width. Both monosporous and disporous development within a surrounding "pseudoplasmodium" was detected. Infections caused moderate hyperplasia and occasional necrosis of the respiratory epithelial cells of the gill. PMID- 2250338 TI - Retained caseous yolk sac in a Burmese python (Python molurus bivittatus). AB - Retained yolk sacs are common in the domestic chicken and account for considerable morbidity and mortality during late embryonic development and within the first 10 days of life. What is believed to be the first recorded instance of a retained caseous yolk sac and its successful surgical removal from a Burmese python (Python molurus bivittatus) is reported. The snake experienced no post operative complications and continues to be well 16 mo following surgery. PMID- 2250339 TI - Congenital osteopetrosis in white-tailed deer (Odocoileus virginianus). AB - Inferior brachygnathia in neonatal fawns occurred sporadically over a 10 yr period in a captive herd of white-tailed deer (Odocoileus virginianus) in southern Ontario. Two fawns submitted for necropsy had marked inferior brachygnathia, protruding tongues, and fractured long bones. Radiographs of the limbs revealed longitudinal striations of relatively translucent immature woven bone that caused loss of distinction between medullary cavities and cortices. Microscopically, there was failure of remodelling of the primary spongiosa and filling of the medulla by cone-shaped chondro-osseous cores. The findings supported a diagnosis of osteopetrosis, usually a hereditary disease characterized by absence of marrow cavities as a result of defective bone remodelling. Osteopetrosis has not been reported previously in deer. PMID- 2250340 TI - On calcium deficiency and brittle antlers. PMID- 2250341 TI - [Tumor control-significance of the stem cell number]. AB - The stem cell number is one of the important factor determining tumor control radiation dose. It is now clear that 50% tumor cell doses in various rodent tumors inversely related to their tumor control radiation doses. Roles of radiation-sterilized cells on the clonogenicity of survived stem cells are controversial, and should be explored by future research. Methodological innovations are also desirable to measure the stem cell number in human tumors. PMID- 2250342 TI - [What is cure of the tumor with radiation therapy? Clinical viewpoint]. AB - Tumors as malignant as lung cancer can be cured by radiation therapy. Local control is the primary requirement for complete cure of the tumor, but the continued presence of the mass demonstrated by imaging techniques does not necessary mean persistence of viable tumor cells. The mass shadow persisting in the region irradiated at a cure dose may simply represent delayed absorption of dead cells so that the patient should be observed for at least 3 months after the therapy. This requires patience on the part of clinitians, but erroneous additional irradiation must be avoided, because excess irradiation can do harm but no good. Radiosensitivity, radioresponsiveness, and radiocurability are all independent characteristics of the tumor. In general, the effects of radiation therapy must be evaluated comprehensively in consideration of these three characteristics of the tumor. Understanding of the natural history of the disease is essential for the treatment of malignant tumors. Therapeutic approach cannot be determined if the natural history of tumor is disregarded. PMID- 2250343 TI - [Biological evaluation of chemo-radiotherapy combined with cisplatin]. AB - Biological basis for the combined chemo-radiotherapy which may be required for the useful application to the radiotherapy combined with cisplatin was discussed. Experimental data have suggested that cisplatin is useful for increasing the therapeutic gain if the tumor is sensitive for cisplatin alone. However, it was revealed from our experiment that a mouse carcinoma as in human tumors contains several clones which differ in their sensitivities to both radiation and cisplatin, and further that the radioresistant clone also showed the resistance to cisplatin. It was considered from both experimental and clinical outcome that the development of more efficient assay method for drug-sensitivity as well as that of therapeutic regimens for preventing cellular proliferation of drug- or radiation-resistant subclones was important. PMID- 2250344 TI - [Hypoxic cell radiosensitizer present status and problems from viewpoint of clinical radiotherapy]. AB - The results of clinical trials of hypoxic cell radiosensitizers were reviewed in order to clarify the present status and problems in this field. Most trials failed to show an effectiveness of the combination, however, some ENT tumors and bladder cancers were improved in local tumor responses and survivals. A selection of the patients suitable for the combination and development of simple method for the selection are indispensable. SERs necessary for clinical radiotherapy are considered to be larger than 1.2 at 2 Gy fraction level. Present hypoxic cell radiosensitizers have no significant effects on alpha values. Since radiation responses at low radiation dose ranges are dominated by alpha values, the chemicals having an effects on alpha values have to be developed. PMID- 2250345 TI - [Thermal radiosensitization in vitro and its implication to radiotherapy]. AB - Thermal radiosensitization and the possible mechanism are reviewed. In vitro studies suggest that hyperthermia can enhance cell killing by radiation resulting in a steeper slope and smaller shoulder of the cell survival curve, compared to the survival were following radiation clone. Molecular studies suggest that inhibition of DNA synthesis and or repair of DNA damage by hyperthermia might be major causes of the thermal radiosensitization. When the curve is fitted by linar quadratic (L-Q) model, a increased number of beta, while relatively stable amount of alpha values are shown for survival curve to radiation combined with hyperthermia. This implies that when a larger radiation dose (greater than or equal to 4 Gy) is combined with hyperthermia, the enhancement would be greater in thermal radiotherapy. PMID- 2250346 TI - [Clinical assessment of thermoradiotherapy of breast cancer and cancer of the urinary bladder]. AB - Non-randomized clinical trials of thermoradiotherapy for breast cancer and carcinoma of the urinary bladder were reported. Thermoradiotherapy was useful for breast cancer treatment in term of (1) increased local control for locally advanced tumors and (2) possibility of reducing dose of irradiation for recurrent tumors following radiotherapy. Tumor response to thermoradiotherapy was dependent on tumor volume and maximum or minimum tumor temperature. Thermoradiotherapy was also effective as a preoperative-treatment for urinary bladder cancer. The incidence of down-staging and degeneration of tumors was significantly higher in thermoradiotherapy than in radiotherapy. These effects were temperature dependent. Patients with T 3-4 NOMO or Grade 3 tumors treated with thermoradiotherapy showed a tendency of increased survival compared with those treated with radiotherapy alone. PMID- 2250347 TI - [Interactions of radiation and biological response modifiers (BRMs) in the treatment of malignant tumor]. AB - This article reports on attempt to characterize the interactions of radiation and BRMs in the treatment of malignant tumor on the basis of our some experimental results. BRMs have a high possibility to enhance radiation effects on tumor cells with in a radiation field and bring some benefits to host tumor immune system with minimizing deleterious effects of irradiation to the immune responses. But it is very difficult to determine the rational design of administration of BRMs to induce the most effective interactions on relevant immune system and other host responses in the combination with radiotherapy. We should make it clear how radiation can be useful to potentiate the tumor antigenecity or antitumor immune responses. PMID- 2250348 TI - [Radiation injury of the normal brain tissue after external radiotherapy of brain tumor]. AB - The calculated dose expressed by neuNSD (or neuret) shows a significant relationship between a therapeutic dose and a post-radiation time in the normal brain injury. An aged patient and a patient with the vulnerable brain in the irradiated field had the high risk of radiation injury. Radiotherapy needs to consider the cost-benefit balance for those risk patients. The hyalinization of the vessels and demyelination were observed even in low-dose radiation areas in non-aged patients, and in aged patients fibrinoid necrosis was observed in low dose radiation areas. The combination of intraarterial chemotherapy and radiotherapy increased the injury of the brain. If the low-density area existed within the irradiated field on CT, it could be a cause of radiation injury. Steroid and anticoagulant drugs should be given to recover from the condition before radionecrosis. PMID- 2250349 TI - [Treatment policies with active intention on radiation therapy in brain tumors and tolerance dose of the nervous system]. AB - For the treatment of brain tumors, radiation tolerance on the central nervous tissues is one of the most serious limiting factor, because glioblastoma has been considered as radioresistant. Radiation therapy in commonly employed dosages for malignant gliomas carries a risk of injury to surrounding cerebral tissues. Therefore, precision radiation therapy concerning that radiation field co-inside with the tumorous lesion is essentially important to intend obtaining an improvement of the local control rate without delayed radiation injuries. In this paper, a review of literatures as for radiation tolerance on the central nervous system and treatment policies with active intention for brain tumors are discussed. PMID- 2250350 TI - [Radiation enteritis: mucosal regeneration and stromal reaction of the small intestine after irradiation]. AB - D-glucose absorption in vivo in mice decreased as a function of dose and time after irradiation returning to normal within a week after irradiation. The lamina propria is seen full of polymorphonuclear leukocytes, other infiltrative cells, capillary and lymphatic network, which seem closely related to chronic enteritis. Since acute and chronic diarrhea after irradiation can be reduced by cholestyramine or acetylsalicylate, malabsorption of bile salts or prostaglandin E of the luminal content has been regarded as a cause of radiation-induced diarrhea. LD 50 of irradiated mice was increased by SOD. From the clinical data, thin physique, previous operation, and total dose of more than 50 Gy could be predisposing factors of radiation-related enteritis. PMID- 2250351 TI - [Tolerance dose of the small intestines and colon in patients with carcinoma of the uterine cervix]. AB - From the clinical data of the 199 patients with carcinoma of the uterine cervix from August 1978 to December 1982 using external irradiation and RALS, the tolerance dose of rectum and sigmoid colon were considered as 65 Gy and 70 Gy, respectively. On the other hand, from the review of 86 patients who had been treated for paraaortic lymph node based on a survey of Kansai Cancer Therapist Group, the tolerance doses of small intestine were considered as 40-50 Gy. For further reassessment of tolerance dose, the analysis of volume factor and basic research for pathogenesis of complication are essential. PMID- 2250352 TI - [Radiation tolerance of normal lung-pulmonary radiation syndrome]. AB - Radiation pneumonitis and radiation fibrosis are two distinct syndromes with probably different target cells. The ultrastructural changes occur rapidly and current evidence suggests that damage to the type II pneumocyte and the endothelial cell is linked to the pneumonia process than the fibrotic. The fibrosis process may be related to the basement membrane of both endothelial cells and alveolar type I cells. Dose time and volume data for tolerance dose are well documented in animals. Many antineoplastic agents enhances radiation lung damage. The pneumonitis and fibrosis will be discussed. PMID- 2250353 TI - [Clinical study on development factors of radiation pneumonitis]. AB - Forty-six lung cancer patients received radiotherapy from 1982 to 1987 were reviewed to analyze the incidence of radiation pneumonitis and the factors which were related to it. The incidence of which evaluated with plain chest X-ray was 54% at 1 month, 78% at 3 months and 89% at 6 months after radiotherapy. The relationship between severity of pneumonitis and several parameters were studied. As a result, six parameters consisting of pre-radiotherapy granulocyte counts, tumor location, T-factor, radiation dose, radiation field size and the combination timing of chemotherapy were found to be contributing factors. PMID- 2250354 TI - [The effect of repeated small doses of radiation on cell killing and repair capacity in plateau phase C3H 10T 1/2 cells]. AB - Using plateau phase C3H 10 T 1/2 cells, we studied the effect of multiple-dose irradiation on the repair capacity of cells after further irradiation. Cells were irradiated with repeated doses of 2.5 Gy delivered two fractions per day at 6 to 7 hours interval. The cell survival after exposure to 1 to 9 fractions was lower above fractions as compared to that predicted by calculating from single dose survival curve by assuming that cells retain their capacity to repair radiation damage after each fraction. Repair kinetics experiments showed that cells were less able to repair only slow type potentially lethal damage after test dose following multiple dose irradiations. Thus, it would appear that an enhancement of the lethal expression of potentially lethal damage of three types of damage may, at least in part, contribute to the difference between the cell survival curve after multiple fractions and that predicted by calculation. PMID- 2250356 TI - [Tolerance dosage of normal tissues by radiotherapy combined with chemotherapy in the group of patients]. AB - Normal tissues have sigmoid dose-response relationships. These relationships are reliably detectable in some clinical and many experimental situations through the aspect of radiobiology. By the way, when the group of patients are treated by radiotherapy combined with chemotherapy, the tolerance dosage of normal tissues in the group is not explained by biological aspect alone. Human tolerance which means the will of patient for the tolerance to the treatment, is the new concept. The compliance to take medicine is the second important problem, when the tolerance dosage of normal tissues in the group of patients treated with combined therapy are discussed. When these new concepts to the normal tolerance dosage, which are human tolerance and compliance, will be scored in the future, these factors will be discussed again about their importance. PMID- 2250355 TI - [Fractionation and radiation injury--clinical aspect]. AB - The late effect of normal tissues in altered fractionation was analyzed with our experience and review in clinical trial. In hypofractionation late effect in normal tissues increased in frequency with increased dose per fraction. In the other hand, the optimal ERD or fractionations in MFD were found in larynx, lung and esophagus. The ERD and the frequency of severe late effect in clinical trial with accelerated or accelerated hyperfractionation tended to be less than those of hyperfractionation. However the tolerance ERD in brain and abdominal organ have not been able to determine due to short life span, combined modality and few clinical trial. PMID- 2250357 TI - [Radiosensitization of mouse intestinal epithelial cells with BudR]. AB - For the radiosensitization of the repair rich epithelial cells of small intestine, BudR (B.U.) was continuously infused into mice. Its uptake into the DNA, as shown by the substitution rate (S.R.) of thymine to B.U., was dose dependent in low dose, but above the 4 mg/d/head it did not increased. The radiosensitization effect was assayed by the clonogenecity of the cells, and (1) the repair capacity (recovery factor, RF.) of the cells and (2) the isoeffect dose (I.D) were obtained. From these data, their enhancement ratios (E.R) were estimated. E.R. by R.F. increased remarkably both in low dose and in low S.R., but showed the plateau at about 10 level after 4 mg/d/h of dose or 10% of S.R. Whereas E.R. by I.D. increased linearly in dose or it did quadratically in S.R. From these results, it was discussed that radiosensitization by debromozation of B.U. was seen in low dose, and the direct cytocidal effect of B.U. became dominant with the dose-increase. Also the clinical application of B.U. was discussed in cell kinetical aspect of B.U. labelling as well as the progress of infusion techniques. PMID- 2250358 TI - [Arterial blood flow changes after hyperthermia on normal liver, normal brain, and normal small intestine]. AB - Arterial blood flow changes are studied after hyperthermia on normal liver, normal brain, and normal small intestine. A small part in left lateral lobe of rat liver was heated by RF capacity heating. Arterial blood flow in heated area of liver decreased to 69.2 +/- 8.1 and 51.3 +/- 6.6 ml/min/100 g dry weight respectively after heating at 43 degrees C for 30 min and 45 min, from 83.1 +/- 2.6 ml/min/100 g dry weight at 37 degrees C. To heat a small part in left hemisphere of rat cerebral tissue, RF interstitial heating device was utilized. Arterial blood flow in heated area increased to 289.1 +/- 41.5 ml/min/100 g dry weight after heating at 42 degrees C for 30 min from 223.6 +/- 18.8 ml/min/100 g dry weight at 37 degrees C. For small intestine heating, water bath was used. Arterial blood flow increased to 6.60 +/- 1.36, 7.44 +/- 1.16, and 11.6 +/- 2.2 ml/min/g dry weight respectively after heating at 39 degrees C, 41 degrees C, and 43 degrees C for 30 min, from 5.04 +/- 0.85 ml/min/g dry weight at 37 degrees C. These data suggest that blood flow changes after hyperthermia differ from tissue to tissue, and require further investigation on the effect of hyperthermia on blood flow changes in liver, brain, small intestine, and other normal tissues. PMID- 2250359 TI - [Physical considerations on the method for improving the outcome of radiation therapy]. AB - The outcome of radiation therapy is closely related to the dose that has been delivered to the target volume and the organs at risk. In this report, sources of errors in dose delivery and their magnitudes at each step of radiation therapy from data acquisition of patient to execution of irradiation, and the methods for reducing the errors are discussed. The influences of systematic or random errors in the target dose level and of dose inhomogeneities throughout the target volume on the dose-effect curve are also described. To improve the outcome of radiation therapy, a constant effort from radiotherapists, physicists and technicians is required for reducing the systematic and random errors at each step of radiation therapy. PMID- 2250360 TI - [Problems and future of radiation oncology in Japan]. AB - The present status and various problems of radiation oncology practice and study in Japan are discussed compared with historical development of radiotherapy in the United States. Besides insufficient resources and personal staffing, traditional thinking and cultural habits have been adversely affecting scientific way of thinking, training of professionals, and daily operation as well as study of radiation oncology in Japan. In the current limited situation, palliative treatment and its systematic, original study should be more emphasized to further develop radiation oncology program and to increase credibility of radiotherapy among medical professions in general. PMID- 2250361 TI - [How is it considered to advance radiotherapy from biological and clinical standpoint of view?]. AB - The main reasons of recent advances of radiotherapy are considered to be due to improvements of therapeutic techniques and therapy machines, but the contributions of radiobiology are thought to be no so great. In the present paper, the history of radiotherapy is reviewed, and several problems to be solved in order to make more effective radiotherapy taken in radiobiological factors was discussed. PMID- 2250362 TI - [Several factors for improving results of radiation therapy]. AB - Various methods have been employed for improving the efficacy of radiation therapy including combined use of radio-sensitizer, chemotherapy, hyperthermia, combination with surgery, intraoperative electron beam therapy, heavy particle therapy, etc. We have evaluated if further improvements in treatment results could be obtained by improving irradiation techniques which are routinely employed in the daily radiation therapy. The results of our evaluation has indicated that therapeutic gains could be raised by: (a) vastly improved radiographic techniques for better visualization of tumor and normal structures, that is, more reliable determination of target volume; (b) improvement of reproducibility of field alignments; (c) improvement of dose distribution by multiportal irradiations. PMID- 2250363 TI - [Multiple primary cancers of the head and neck]. AB - From January 1985 to June 1988, the authors have treated 138 cases of head and neck cancers. Among this number, six cases (4.3%) involved patients with a multiple primary cancer. With the exception of 1 case, all patients were male with a history of heavy smoking and excessive drinking. The primary cancer of the head and neck was most frequently located in the hypopharynx, and a secondary multiple cancer in the upper digestive tract especially the esophagus. Although we were unable to detect an early esophageal cancer by an esophagogram in some cases, each lesion could be detected by using lugol stain and gastrointestinal endoscopy. PMID- 2250364 TI - [A carcinoma of the reconstructed gastric tube after a radical esophageal cancer operation]. AB - Reported are five patients who developed a carcinoma of the reconstructed gastric tube. In 3 of the 5 patients, the esophageal cancer was preceded by a gastric cancer, and the intervals before the gastric cancer was detected were 34, 24, and 60 months. The gastric tube the had been reconstructed by the retrosternal rout was resected with a median sternotomy in cases 1 and 2. In case 3, since a liver and lung metastasis had been detected by routine examination, surgery was not performed. Cases 4 and 5 had an esophageal cancer associated with a simultaneous early gastric cancer located in the lesser curvature of the upper body. Thus, a esophagectomy and a partial gastrectomy were performed. Twenty-eight and 21 months later, respectively, an early gastric cancer was found at the stump of the gastric tube that had been reconstructed by the retrosternal route. Endoscopic laser therapy was subsequently employed for both patients. Because of these findings, the author have concluded that postoperative serial examination of the gastric tube are very important, since cases of a gastric tube cancer are increasing. PMID- 2250365 TI - [A simple mathematical model for a quantitative evaluation of mass screening for detection of cancer]. AB - In Japan, where the mass screening of various cancer are actively pursued under the auspices of the Adult Health Promotion Act of the Japanese Government, the incidence rate of various cancers has been undergoing a drastic change since 1960. Cancers of stomach and uterine cervix, which had predominated, are decreasing steadily, whereas lung, colon and breast cancers are rapidly increasing. To provide therapeutic care on the basis of accurate data, the mass screening system must be re-evaluated so as to maintain its effectiveness and efficiency. For this purpose, a simple, deterministic model is proposed to measure the cost-effectiveness of the mass screening quantitatively. The effect of the screening is estimated by the net number of lives that have been saved by the screening, with the final result being shown as the cost require to save one life of a certain age and sex. The model, although only an approximation, fits all kinds of cancers by changing the parameters employed in the mathematical equation, and has been found useful for forecasting the results of future mass screenings for the detection of cancers in Japan. PMID- 2250366 TI - [A case of two primary carcinomas: thyroid papillary carcinoma with anaplastic transformation of metastatic cervical lymph node and breast cancer]. AB - Reported is the case of a 70-year-old woman who, on diagnosis, was found to have a papillary carcinoma of the thyroid gland that showed an anaplastic transformation of a metastatic lesion of the right cervical lymph node. The primary lesion, however, contained no anaplastic areas. Simultaneously, she also was found to have a primary carcinoma of the left breast, an invasive ductal carcinoma. She thus received a total thyroidectomy with a right cervical node dissection, a modified radical mastectomy, and irradiation of the right cervical area, but no intensive chemotherapy was performed. Six months after the thyroidectomy, the anaplastic carcinoma caused her death. On autopsy, it was found to have involved the right cervical area, the lungs, the mediastinum, the right axilla, and the right kidney. PMID- 2250368 TI - [A diffuse, pleural, malignant mesothelioma kept in long remission by chemotherapy combining pirarubicin and cisplatin]. AB - Reported is the case of a 66-year-old male with a diffuse, pleural, malignant mesothelioma that has been successfully treated by combining cisplatin and doxorubicin. The patient received 100 mg of cisplatin and 50 mg of doxorubicin every 5 weeks, after which a regression of the tumor and a pleural effusion decrease was observed. After partial remission was achieved, the dosage was changed to 50 mg of cisplatin and 50 mg of pirarubicin on a five-week cycle. This led to a partial remission of two-years duration and the abatement of a doxorubicin-induced alopecia. The authors thus have concluded that a combined therapy of doxorubicin and cisplatin is effective for treating a malignant mesothelioma, and that pirarubicin is superior to doxorubicin with reference to side effects. PMID- 2250367 TI - [Esophageal carcinoma with hypercalcemia that appeared to be caused by prostaglandin E2 produced by the tumor cells]. AB - Discussed is the case of a 50-year-old man with a well advanced esophageal carcinoma who, during his final clinical course, suddenly developed hypercalcemia (max: 15.0 mg/ml). His serum parathyroid hormone level, however, remained within normal limits. On autopsy, an extensive metastasis to many organs and lymph nodes was noted but no evidence of a bone metastasis. Nude mice bearing the same tumoral tissue were found, on autopsy, to have similarly developed hypercalcemia and cells that were cultured were found to produce an excessive amount of Prostaglandin E2 (PGE2). These findings suggest that this humoral hypercalcemia of malignancy (HHM) was caused by excessive PGE2 produced by the tumor cells, although other possible factors should be investigated. PMID- 2250370 TI - [Adenomyoma in association with early gastric carcinoma]. AB - Described is a gastric adenomyoma associated with superficial gastric adenocarcinoma that was found in a 72-year-old male. This uncommon benign gastric lesion is believed to be developmental in origin and sometimes categorized as belonging to a subgroup of a heterotopic pancreas. Besides its rarity, an adenomyoma is also known to be a possible cause of a gastric malignancy. Although the focus of the carcinoma in our case was located in the center of the adenomyoma, this finding cannot support the etiology of a gastric carcinoma originating in an adenomyoma. However, the present case appears to imply some relationship between an adenomyoma and a gastric carcinoma. PMID- 2250369 TI - [A case of colony stimulating factor (CSF) producing gastric carcinoma]. AB - A gastric carcinoma associated with marked leukocytosis is reported. The case involved a 70-year-old male who was admitted to Akita Kumiai General Hospital because of general fatigue and vertigo in October, 1989. A palpable, hard, uneven mass was found in the epigastrium. Further, an upper gastrointestinal series revealed a large filling defect in the gastric body. Also, an endoscopic examination disclosed an uneven mass, and specimens that were biopsied showed an adenocarcinoma. The white blood cell (WBC) count was 45,800/microliter and had a 96% presence of neutrophils, and an examination of the bone marrow showed excessive myeloid hyperplasia. The WBC gradually increased, reaching up to 67,800/microliter. Finally, an EIA assay of the serum colony stimulating factor (CSF) disclosed a marked increase. After a gastrectomy, the WBC promptly decreased to the normal range and the CSF activity in a supernatant of a tumor cell-conditioned medium showed a higher value. Thus, this tumor was diagnosed as being a CSF-producing gastric carcinoma. PMID- 2250371 TI - [An early cancer in adenoma of the papilla of Vater]. AB - A 61-year-old male was admitted to our hospital with a complaint of epigastric discomfort and back pain. Chronic pancreatitis was suspected after an abdominal US study. Therefore, an ERCP study was performed. Macroscopically, the papilla of Vater showed an irregular shaped swelling. An ERCP X-ray revealed no abnormal findings, but biopsied specimens from the papilla showed a well differentiated adenocarcinoma in the adenoma, so that a pancreatoduodenectomy was performed. The lesion was 15 x 9 x 6 mm in size, and a histological examination revealed that a minor portion of the tumor was a carcinoma while the major portion was an adenoma, and the invasion as being d0 panc0 n0. PMID- 2250372 TI - [The complete remission of recurrent sweat gland carcinoma by radiotherapy combined with hyperthermia]. AB - The authors describe a case of a sweat gland carcinoma that underwent complete remission after treatment with radiotherapy and hyperthermia. This sweat gland carcinoma had been thought to be unamenable to any therapeutic treatment. Based on this result, the authors feel that radiotherapy combined with hyperthermia may be effective for the treatment of a sweat gland carcinoma. PMID- 2250373 TI - [An autopsy case of multiple myeloma accompanied by extensive nodular infiltration into the extraskeletal tissue]. AB - Discussed is the case of a 41-year-old Japanese man dead at 4 months after start of his clinical course of multiple myeloma of the Bence-Jones protein lambda type of the skull. Autopsy findings revealed that atypical plasmacytes had infiltrated extensively into the testes, the retroperitoneum, including the pancreas and the renal pelvis, the bilateral pleura, the right subclavian soft tissue, and the meningism, but not to the liver, spleen, and lymph nodes. In both testes, which weighted 120 g and 100 g, respectively, myeloma cells were found disseminated throughout the testicular tissue. Such a testicular involvement in cases of a multiple myeloma is extremely rare. The pertinent literature also is reviewed. PMID- 2250374 TI - [An autopsy case of postirradiation cutaneous angiosarcoma of the hip]. AB - Presented is the case of a 63-year-old woman who developed a cutaneous angiosarcoma of the hip after receiving adjuvant radiation therapy for a squamous cell carcinoma of the uterine cervix after a hysterectomy. The time lapse between the radiation therapy and the occurrence of the angiosarcoma was 15 years, and its systemic metastasis was seen on autopsy. This autopsy was carried out 26 years after the patient had received the initial irradiation and no recurrence of the uterine cancer was found. Factor involved in the etiology of an angiosarcoma are discussed, and 34 previously reported cases of a postirradiation angiosarcoma are reviewed. PMID- 2250375 TI - [An experimental study of the effect of perfusion of duodenal juices in the vagally innervated antral pouch upon gastric endocrine and exocrine function]. AB - Vagally innervated antral pouches were created in adult mongrel dogs, the interiors of these antral pouches were perfused with glycocholate, taurocholate, canine bile and human pancreatic juice, and antral function was investigated from the viewpoint of gastric endocrine and exocrine response. Perfusion with glycocholate and taurocholate of 20 mM induced a significant increase in gastric acid secretion as well as serum gastrin secretory response. Perfusion with canine bile and human pancreatic juice induced a pronounced increase in serum gastrin levels as well as gastric acid secretion starting immediately after the beginning of perfusion, and serum gastrin secretory response also displayed a marked increase. These results demonstrated that the regurgitation into the stomach of duodenal fluid containing bile and pancreatic juice, constitutes one factor causing increased serum gastrin levels and gastric acid secretion. PMID- 2250376 TI - [Prevention of alcohol-induced gastric mucosal injury by prostaglandin E-1]. AB - Effects of ethanol and prostaglandin on the glycoprotein synthesis in the gastric mucus cells have been evaluated. The rat gastric mucosal cell were subjected to a short-term tissue culture in the presence of ethanol and prostaglandin E2 (Ornoprostil), using [3H]-proline, [3H]-palmitic acid, [3H]-galactosamine. Low concentration of ethanol (0.05-0.01 M) stimulated the glycoprotein synthesis, but higher concentration of ethanol (0.5-1.5 M) caused a marked reduction in the glycoprotein synthesis. Addition of prostaglandin E2, especially addition of prostaglandin prior to ethanol treatment, has improved the glycoprotein synthesis and secretion in the presence of ethanol. It was suggested that addition of prostaglandin resulted in the stabilization of the synthesis and secretion of the mucus glycoprotein in the presence of ethanol. PMID- 2250377 TI - [Immunohistological study for the ras oncogene products in colorectal cancer]. AB - By using anti-NHK-ras and K-ras monoclonal antibodies, paraffin-embedded tissue specimens of 70 cases of colorectal cancers were immunohistologically examined. Correlation between incidence of expression of these oncogenes and either of postoperative survival rate and stage of colorectal cancer were calculated. The positive rate of anti-NHK-ras and K-ras staining were correlated with maximum diameters of tumor, staging, degree of Dukes classification and depth of invasion. Positive and negative rates of between NHK-ras and K-ras staining were well coincident. The cumulative postoperative survival rate of negative cases for anti-K-ras staining showed a significantly higher survival rate than that of the positive cases. PMID- 2250378 TI - [A proposal for a new histological criteria and staging of non-specific duodenitis (NSD)]. AB - Using normal duodenal mucosa (28 cases), initial duodenal ulcer-associated duodenitis (IUAD, 14 cases; 3 active, 8 healing and 3 scarring or healed ulcers) and recurrent duodenal ulcer-associated duodenitis (RUAD, 16 cases; 5 active, 8 healing and 3 scarring or healed ulcers), a new histological criteria and staging of NSD was tried to be made with discriminant analysis. As a result, it is concluded that neutrophilic cell infiltration in the stroma (Ne), gastric superficial epithelial metaplasia (GM), height of villus-crypt unit (HVC) and width of villus (WV) are important factors for histological criteria of NSD, and that number of neutrophilic cells in the stroma (NeS) and percentage of GM in the villus-crypt unit (%GM) are important factors for histological staging of NSD. PMID- 2250379 TI - [The changes in hepatic hemodynamics and hepatic energy charge (blood ketone body ratio) induced by vasopressin infusion in chronic liver disease]. AB - We evaluated the changes in the hepatic hemodynamics and blood ketone body ratio (KBR) induced by vasopressin in 40 patients with chronic liver diseases to clarify the effect of hepatic blood flow on hepatic energy charge expressed by KBR. Following infusion of vasopressin, the rate of decrease in portal blood flow in liver cirrhosis (LC) was significantly lower than that in chronic hepatitis (CH). Moreover, the blood flow in the hepatic artery after vasopressin infusion was greater in LC than in CH. As a result, the total hepatic blood flow, which was the sum of the flow in the above two vessels, after vasopressin infusion was greater in LC than in CH but the decrease in the blood KBR was not significant in LC. Thus, vasopressin appears to be hemodynamically safe in patients with LC, but caution is needed since it may decrease blood pressure, total hepatic blood flow and KBR in some LC patients. PMID- 2250380 TI - [The role of cholesterol and phosphatidylcholine on very low density lipoprotein secretion from rat hepatocytes]. AB - The role of cholesterol and phosphatidylcholine on hepatic very low density lipoprotein secretion was investigated with rat hepatocytes. Hepatic very low density lipoprotein secretion (apo B, apo E, cholesterol, triglyceride, phosphatidylcholine) was decreased by the reduction of hepatic phosphatidylcholine content. However, cholesterol loading into hepatocytes did not affect hepatic very low density lipoprotein secretion. Hepatic apolipoprotein contents were constant and were not influenced by a change of hepatic cholesterol and phosphatidylcholine contents. These results suggest that lipids, which are constituents of lipoproteins, play different roles on hepatic very low density lipoprotein secretion. PMID- 2250381 TI - [A case of Dieulafoy's ulcer--angiographic demonstration of the bleeding artery]. PMID- 2250382 TI - [A case of ileal carcinoid tumor with mesenteric retraction]. PMID- 2250383 TI - [A case of retroperitoneal schwannoma considered to be of celiac plexus origin (vagus nerve)]. PMID- 2250384 TI - [Stress and stomach lesion]. PMID- 2250385 TI - [The digestive system and aging]. PMID- 2250386 TI - [Intrahepatic calculi]. PMID- 2250387 TI - [Clinical significance and progress of the study on hepatic and portal circulatory disorders]. PMID- 2250388 TI - [The study on descriptive epidemiology of peptic ulcer in Hokkaido]. AB - We previously reported that the reported that the ratio of gastric ulcer to duodenal ulcer in Hokkadio was higher than that in other area of Japan. This time, we analysed peptic ulcer cases of five hospitals in Hokkaido on the point of geographical and pathological distribution. When we divided these hospitals into two groups (in Sapporo city and other provincial areas) and calculated the sex and age adjusted ratio of gastric ulcer to duodenal ulcer in each group, we found the difference between the two groups (in Sapporo city: 2.26, other provincial area: 5.86) and thought the feature of high ratio the feature of the provincial hospitals. This difference in Hokkaido may be due to the environmental factors for peptic ulcer or the biased sampling of the study. The further study is needed to reveal the geographical and pathological distribution of this disease. PMID- 2250390 TI - [Correlation between Campylobacter pylori and chronic atrophic gastritis]. AB - The correlation between urease activity of Campylobacter pylori and atrophic gastritis was studied. On the basis of fundamental study on the optimal pH of C. pylori urease activity, urease activity of 38 biopsied specimens were measured under pH 5 condition, and compared with the positive ratio of C. pylori. In this study, sensitivity was 86.7%, and specificity was 87.0%, respectively. Mean urease activity of C. pylori positive specimens was 3.69 mIU/mg protein, and under this condition, C. pylori was likely to produce ammonia of 0.0218 mumole per minute, enough to damage the gastric mucosa. In addition, there was encountered high urease activity in the specimens which showed moderate glandular atrophy and severe mucosal inflammation. In conclusion, urea-urease-NH3 sequence is most likely to have some association with gastric glandular atrophy. PMID- 2250389 TI - [Evaluation of SOD activity in gastric mucosa of hemorrhagic shock rats]. AB - Superoxide dismutase (SOD) exogenously administered has been documented to protect gastric mucosa against ischemia-reinfusion injury by scavenging oxygen radicals. However, the changes in levels of endogenous SOD in ischemic gastric mucosa are not known. To evaluate this, the present study was designed. METHODS: Fasted and anesthetized SD rats were given 0.1 N HCl i.g. and received the following procedures. Study 1: (1) Ischemia group--25 min after acid instillation, blood pressure was reduced to 20-30 mmHg for 20 min. (2) Ischemia Reinfusion group--5 min after acid administration, rats received the same hypotension as above followed by reinfusion of shed blood for 20 min. (3) Control group-Rats were killed 45 min later without hypotension and reinfusion. Study 2: Three groups of rats treated with the same procedures as in Study 1 were given allopurinol (50 mg/kg/day) i.g. once daily for 2 days prior to the experiment. All rats were killed by exsanguination from the carotid artery to avoid as much as possible contamination of gastric mucosal samples with red blood cells rich in SOD. The supernatants of the corpus and antral mucosa homogenized were prepared for measuring their SOD activity using the nitrite method modified by Oyanagui. RESULTS: SOD activity in the gastric mucosa significantly increased in both the Ischemia (Ische.) and Ischemia-Reinfusion (I-R) groups compared to the control (Ische. vs. I-R vs. Cont'l: corpus-123.4 +/- 4.8 vs. 127.4 +/- 3.6 vs. 96.9 +/- 4.4 NU/Mg protein; antrum-71.6 +/- 2.8 vs. 81.4 +/- 6.8 vs. 62.1 +/- 3.1 NU/mg protein). No increase in SOD activity was observed in rats pretreated with allopurinol. CONCLUSION: SOD activity increases with oxyradicals generation in the rat stomach subjected to either hemorrhagic ischemia alone or hemorrhagic ischemia plus reinfusion. This also suggests that oxyradicals are generated even in the ischemic period. PMID- 2250391 TI - [Analysis of subsets of colonic mucosal lymphocyte in ulcerative colitis by two color flow cytometry]. AB - To assess how the immunological events occur in the colonic mucosa in patients with ulcerative colitis, it is thought to be important to evaluate the subpopulations and/or subsets of mucosal lymphocytes. In this point of view, we assayed those by lymphocyte isolation techniques and two color flow cytometry. Although our results showed no disease-specific abnormalities of the percentages of CD3, CD4, CD8, CD20, and HLA-DR (+) cells in PBL (peripheral blood lymphocyte) nor CML (colonic mucosal lymphocyte), these subsets of CML appeared to be altered according to the grade of severity of inflammation. In our cases, the HLA-DR (+) cell and CD4 population were larger in severely inflamed mucosa. Furthermore, fluorescence intensities of HLA-DR antigen of CD20 population in CML were greater than those in PBL. These results suggest that the B cell-mediated mechanisms may play an important role in maintaining the severe inflammation, and the clinical significance of these studies are discussed. PMID- 2250392 TI - [Clinical study of male patients with primary biliary cirrhosis (PBC)]. AB - We studied 10 male and 23 female patients with PBC to determine whether the clinical and histological features of this disease differed in male and female patients. There were no significant difference between men and women in age distribution and biochemical examinations. In female patients, autoimmune associated conditions such as sicca syndrome, Raynaud syndrome and arthritis were observed 22%, 13% and 36%, respectively. By contrast, no male patients developed those conditions. 80% of the male patients and 70% of the female patients belonged to asymptomatic PBC, and early histological stage, such as Scheuer's I and II were observed 90% of the male patients and 78% of the female patients, respectively. No male patients showed clinical or histological progression during follow-up period (median was 64 months). Nevertheless, not a few female patients showed progression including 3 cases who died during the follow-up period (median was 47 months). We concluded that male patients with PBC tend to have favorable prognosis comparing to female patients. PMID- 2250393 TI - [Serum bilirubin subfractionation by high-performance liquid chromatography in patients with fulminant hepatic failure]. AB - Serum bilirubin subfractionation, using high-performance liquid chromatography (HPLC), was carried out and clinically evaluated in 9 patients with fulminant hepatic failure (FHF). Serum unconjugated bilirubin (UCB), C-8 bilirubin mono conjugate (MBC), C-12BMC and bilirubin di-conjugate (BDC) were quantified by the alkaline methanolysis-HPLC method described by Blanckaert. Similar studies were performed in 10 patients with acute hepatitis (AH) and 6 patients with obstructive jaundice and the results were compared. In patients with rising serum bilirubin, the serum C-12BMC/C-8BMC ratio was calculated to be as follows: 2.10 +/- 0.21 for FHF, 1.05 +/- 0.34 for AH and 0.81 +/- 0.08 for obstructive jaundice, respectively. A significant differences were observed between FHF and AH (P less than 0.01). As there was almost no overlapping, it was considered that this determination is useful for the differential diagnosis of jaundiced patients, especially, in those patients with AH whose sera show a prolonged prothrombin time lower than 40%, and there is a concern that they may develop FHF. The calculation of C-12BMC/C-8BMC allows us to make a differential diagnosis between AH and FHF at an early period in the development of the disease, and it was proved that serum C-12BMC/C-8BMC ratio can reflect the magnitude of hepatocyte damage as well as bilirubin metabolism disturbance. PMID- 2250394 TI - [Gastric ulcer associated with allergic granulomatous angitis (Churg-Strauss syndrome)--report of a case]. PMID- 2250395 TI - [A case of Crohn's colitis with cecal perforation and abnormalities of coagulation and fibrinolytic system]. PMID- 2250396 TI - [Leiomyoblastoma of the jejunum, report of a case]. PMID- 2250398 TI - [A case of liver choriocarcinoma]. PMID- 2250397 TI - [A case of autoimmune hepatitis developing simultaneously with exacerbation of Felty's syndrome]. PMID- 2250399 TI - [A case of solitary tuberculoma of the liver and a review of the Japanese literature on the morphological characteristics in the images]. PMID- 2250400 TI - [A flexible local injection needle for continuous measurement of intravascular oesophageal variceal pressure (IOVP)]. PMID- 2250401 TI - Stable isotope 15N-urea and clinical research in nephrology. AB - Stable isotope 15N-compound, 15N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. 15N-urea incorporation into plasma albumin in addition to plasma 15N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered 15N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through 15N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal. Therefore, administration of 15N-compound to human subjects may contribute to provide us the important informations on nitrogen metabolism. For instance, urea kinetics are described in the endstage chronic renal failure in this review. However, less expensive 15N-compounds should be provided and more simple but accurate measurement of 15N activity should be developed for the further clinical application of the stable isotope. PMID- 2250403 TI - Osseous changes and abnormalities of mineral metabolism in daunomycin rats. AB - We examined whether daunomycin rats could be used as an experimental model of human chronic renal failure in terms of their osseous changes and mineral metabolism. The daunomycin rats revealed hyperphosphatemia and osteodystrophic bone changes. In this respect, they were similar to human chronic renal failure. A high calcium level was found in the daunomycin rats at first due to the effect of the daunomycin injection, but later there was a lower calcium level than in the control rats due to chronic renal failure. We conclude that daunomycin rats can be successfully used as an experimental model of chronic renal failure from the standpoint of their osseous changes and mineral metabolism. PMID- 2250402 TI - Streptococcal type-specific antibody in patients with glomerulonephritis (2): Correlation to their histological types. AB - Using the PHA method, streptococcal type-specific antibody was studied in sera from 230 patients with various types of nephritis diagnosed by renal biopsy in order to clarify the relationship between streptococcal infection and the histological types of glomerulonephritis. Two or more serologic types of streptococcal type-specific antibodies with high titers (1:384 or more) were significantly increased in patients with MGA, FGS, PGN, endocapillary proliferative GN, MPGN and IgA GN as compared with those in healthy subjects. Two or more serologic types having high titers (1:384 or more) were significantly increased in MGA, PGN, MPGN and IgA GN as compared with MN. The highest titers (1:768 or more) of streptococcal type-specific antibodies were significantly more frequent in endocapillary proliferative GN as compared with healthy subjects, and such titers were significantly increased in endocapillary proliferative GN and MPGN as compared with MN. The frequency of detection of streptococcal serologic types having high titers (1:384 or more) as found in patients with various nephritis, was in the order of Types 18, 3, 30, 1, 12, 10, 6 and 37, and more than half of the nephritogenic types were included in these serologic types. The above data, which suggest a higher probability of contact with nephritogenic strains during alternative establishment of streptococci by different serologic types, may indicate a close relationship of streptococcal infections with MGA, PGN, MPGN, IgA GN, FGS and endocapillary proliferative GN. PMID- 2250404 TI - Effects of low protein diet in puromycin aminonucleoside-induced nephrotic rats. AB - Wistar rats were injected with puromycin aminonucleoside (PAN) to induce massive proteinuria and were raised on a low protein diet to determine whether the urinary protein excretion might be reduced. Although PAN nephrotic rats fed with a normal protein diet containing 20% protein (group A) did not show any reduction of their urinary protein excretion, PAN rats fed with a low protein diet containing 6% protein (group B) revealed a marked reduction at day 9 of the present study in comparison with group A. The total serum protein levels were low in groups A and B as compared to group C, the non-treated control. However, group A recovered to normal levels at day 13. In terms of the absolute amount of oral protein intake, marked differences were observed between groups B and C, but little difference was observed between groups A and C. The body weight in all three groups was decreased at 8 days after the start of this study. The serum levels of creatinine were elevated to 1.1 +/- 0.3 mg/dl and 1.0 +/- 0.2 mg/dl in groups A and B, respectively, on day 7, but abruptly recovered to normal levels by day 12. These data indicate that the decreased urinary protein excretion in group B might be dependent on the total protein volume intake, and not on the renal function nor serum levels of total protein. PMID- 2250405 TI - Nodular glomerulosclerosis in a patient showing impaired glucose tolerance. AB - We report a case showing typical diabetic nodular glomerulosclerosis without retinopathy or other apparent clinical findings of DM except for impaired glucose tolerance. The 57-year-old man had a family history but no personal history of DM. In an extensive examination for DM, the results of funduscopy, daily profile of serum glucose and hemoglobin Alc were entirely within normal limits. However, the oral glucose tolerance test was abnormal. A renal biopsy showed typical nodular lesions (Kimmelstiel-Wilson's lesions). Previously, the interesting feature of transient proteinuria had been recognized. Although hypocellular nodular lesions by light microscopy are characteristic of diabetic nephropathy, renal amyloidosis, carbon disulfide intoxication, multiple myeloma and light chain disease, we concluded that the present lesions had resulted from diabetic nephropathy based on the family history, patient history, impaired glucose tolerance, immunofluorescent findings and electron microscopic observations. PMID- 2250406 TI - Administration of calcium carbonate with adequate doses of vitamin D metabolite to patients on hemodialysis improves mild secondary hyperparathyroidism. AB - The effects of CaCO3 with vitamin D metabolite and without vitamin D metabolite on secondary hyperparathyroidism were investigated in 18 patients undergoing maintenance hemodialysis. 9 patients (Group 1) were treated with 1 microgram/day 1 alpha (OH)D3 and 2 g/day Al(OH)3, and the other 9 patients (Group 2) received 2 g/day Al(OH)3 without vitamin D metabolite. CaCO3 at amounts of 3 g/day was subsequently administered to all patients instead of Al(OH)3. The levels of mid portion-parathyroid hormone (M-PTH) in Group 2 and of 1,25-dihydroxyvitamin D3 in Group 1 during the baseline period were significantly increased as compared to those in the other group, respectively. In Group 1 only, the level of serum ionized calcium was appreciably elevated at the 4th and 12th weeks as compared to the baseline value, and the level of M-PTH was significantly decreased at the 4th and 12th weeks as compared to the baseline value. The levels of serum phosphate, calcitonin, magnesium and bicarbonate in both groups at the 4th and 12th weeks were not appreciably different from the baseline values. The level of serum aluminum in all patients of both groups were reduced at the 12th week as compared to the baseline values. A close correlation was recognized between M-PTH and the level of intact parathyroid hormone. It is concluded that prescription of 3g/day CaCO3, together with adequate doses of vitamin D metabolite, can ameliorate mild secondary hyperparathyroidism. PMID- 2250407 TI - Do the H2-receptor antagonists, cimetidine and famotidine, modify the degree of renal recovery following renal insult? AB - The effects of two different H2-receptor antagonists, cimetidine and famotidine, on the acute renal failure induced by 20 min of renal artery occlusion and gentamicin (240mg/kg BW, s. c., for 3 days) were investigated in Sprague-Dawley rats. The animals were treated with either cimetidine (80 or 160 mg/kg BW) or famotidine (4 or 8 mg/kg BW) mixed in the drinking water for 7 days. The low dose of cimetidine and famotidine did not alter the renal function in the absence of renal trauma. However, the high dose of cimetidine or famotidine decreased the GFR by 32% and 22%, whereas RPFR increased by 46% and 62%, and % FENa by 92% and 558%, respectively. The data for the renal function obtained 24 hrs after 20 min of renal ischemia demonstrated a decrease of 54% in GFR, a decrease of 47% in RPFR and an increase of 370% in %FENa over the non-ischemic control values (p less than 0.05). Cimetidine (80 mg/kg BW) or famotidine (4 mg/kg BW) did not modify the recovery of renal function following the ischemic insult, showing 55% and 539% decreases in GFR, 74% and 101% increases in RPFR, and 393% and 461% increases in %FENa over the non-ischemic control rats, respectively. Famotidine reduced the decrease in RPFR significantly during the recovery period following ischemia. In the gentamicin study, gentamicin treatment was found to lower the renal function significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250408 TI - Purification and biochemical characterization of reno-ferredoxin from bovine kidney mitochondria. AB - Bovine reno-ferredoxin was purified from kidney mitochondria by an improved method that included hydrophobic and ion-exchange chromatography on Toyopearl gels. The optical absorption spectrum of the oxidized reno-ferredoxin revealed two peaks, at 414 and 455 nm in the visible region. The minimum molecular weight of the ferredoxin was 12,900 Da by SDS-polyacrylamide gel electrophoresis. The amino acid residues of the NH2-terminal sequence of the ferredoxin were investigated using by a gas-phase sequencer. Bovine reno-ferredoxin and adreno ferredoxin showed almost identical NH2-terminal amino acid sequences. Reconstitution of the 25-hydroxyvitamin D3-1 alpha -hydroxylase system was performed with the following three components: NADPH-ferredoxin reductase from bovine kidney mitochondria, reno-ferredoxin, and cytochrome P-450(D1 alpha) from bovine kidney mitochondria. The results demonstrated that the reno-ferredoxin was essential for the 1 alpha-hydroxylase activity of 25-hydroxyvitamin D3. PMID- 2250409 TI - Fiberoptic transurethral lithotripsy prefers smaller impacted ureteral calculi rather than large renal stones. AB - A total of 30 patients with urolithiasis underwent 35 sessions of fiberoptic transurethral lithotripsy (f-TUL) involving electrohydraulic lithotripsy. There were 11 patients with nephrolithiasis including 4 with staghorn calculi and 19 patients with ureterolithiasis which were all located above the pelvic brim. A fiberoptic nephroureteroscope (URF-P) was successfully introduced up to the stone in all but 2 cases (93.3%). Of the 28 patients with successful introduction, 21 received a single session of f-TUL for complete fragmentation of their stones, which measured less than 16 x 9 mm by radiography. Three patients with larger renal stones (greater than or equal to 17 x 9 mm) underwent 2 sessions of f-TUL for complete fragmentation. The remaining 4 patients who had staghorn calculi (greater than or equal to 38 x 33 mm) received 1 session of f-TUL with partial fragmentation; then 3 were sent to an ESWL clinic with good results, while the other patient received 2 more sessions of f-TUL and formed a stone street. Attempts were subsequently made to destroy the latter by ESWL but were unsuccessful. In conclusion, f-TUL appears to be most suitable for smaller impacted ureteral calculi above the pelvic brim. PMID- 2250410 TI - Exercise-induced acute renal failure in 3 patients with renal hypouricemia. AB - Three cases of exercise-induced non-oliguric acute renal failure in patients with renal hypouricemia, an isolated defect of the renal urate transport system, are described. During acute renal failure, the serum uric acid levels were 5.6, 2.7 and 5.8 mg/dl, respectively, and were within normal limits. The values representing the fractional excretion of uric acid (FEUA) were 28.7, 60.0 and 12.7%, with accompanying serum creatinine levels of 8.1, 3.9 and 3.3 mg/dl, respectively. After recovery, the serum uric acid fell to 0.6, 0.7 and 1.0 mg/dl and the FEUA increased to 79.3, 52.8 and 43.2%, respectively. Two of the patients examined exhibited decreased reabsorption of filtered urate. These 3 examples of renal hypouricemia represented 23% of 13 cases of mild exercise-induced acute renal failure encountered within our experience. PMID- 2250411 TI - Compensatory hypertrophy of renal grafts with triple drug therapy. AB - The kidney volume after transplantation was compared in two groups, one treated by conventional immunosuppression and the other receiving small amounts of ciclosporin (CsA) together with azathioprine and steroid (the so-called triple therapy). Fourteen pairs of donors and recipients were investigated in each group. The kidney volume was measured, using computed tomography (CT scan), before and after transplantation in the donors and after transplantation in the recipients during the allograft rejection-free period. The graft volume at 2-3 months after transplantation was smaller (215.9 +/- 30.9 ml, mean +/- SD) in patients who received small amounts of ciclosporin A (CsA) together with azathioprine and steroid than that (270.9 +/- 75.0 ml) in those treated by conventional immunosuppression. The remaining kidney in the donor after transplantation underwent a similar increase in volume in the conventional and triple therapy groups. It is suggested that even a small amount of CsA can significantly limit the compensatory renal growth. PMID- 2250412 TI - A case of nephrotic syndrome due to alpha-mercaptopropionyl glycine in a patient with familial cystinuria. AB - A 26-year-old male with nephrotic syndrome (NS) due to alpha-mercaptopropionyl glycine (MPG) is described. In March, 1988, he was diagnosed as having familial cystinuria after receiving urolithiasis treatment since December, 1985. Massive proteinuria and slight pedal edema were noted. Nephrotic syndrome was suggested and renal biopsy was performed. The renal pathological finding demonstrated membranous glomerulonephritis (MN) at stage I. This case was defined as NS clinically associated with MPG, and glucocorticoid intake was initiated. The response to the glucocorticoids was fairly good with no clinical problems after discontinuation of MPG, and the cystinuria was maintained with alkaline medication. The patient's parents and younger brother were suggested and confirmed to have cystinuria based on urinary aminogram analysis, but displayed no symptoms. We present a rare case of NS due to MPG therapy in a patient with familial cystinuria. However, the mechanism of onset remains unclear. PMID- 2250413 TI - [Effects of attitude formation, persuasive message, and source expertise on attitude change: an examination based on the Elaboration Likelihood Model and the Attitude Formation Theory]. AB - The purpose of this study was to investigate how attitude change is generated by the recipient's degree of attitude formation, evaluative-emotional elements contained in the persuasive messages, and source expertise as a peripheral cue in the persuasion context. Hypotheses based on the Attitude Formation Theory of Mizuhara (1982) and the Elaboration Likelihood Model of Petty and Cacioppo (1981, 1986) were examined. Eighty undergraduate students served as subjects in the experiment, the first stage of which involving manipulating the degree of attitude formation with respect to nuclear power development. Then, the experimenter presented persuasive messages with varying combinations of evaluative-emotional elements from a source with either high or low expertise on the subject. Results revealed a significant interaction effect on attitude change among attitude formation, persuasive message and the expertise of the message source. That is, high attitude formation subjects resisted evaluative-emotional persuasion from the high expertise source while low attitude formation subjects changed their attitude when exposed to the same persuasive message from a low expertise source. Results exceeded initial predictions based on the Attitude Formation Theory and the Elaboration Likelihood Model. PMID- 2250414 TI - [Connection between finger task movements and contralaterally associated movements in children]. AB - Two experiments were carried out to investigate the connection between finger task movements (TM) and contralaterally associated movements (CAM). In Experiment I, 40 children ranging in age from five to six were required to play "marbles" (TM) with the right thumb or forefinger, while two investigators checked CAM on their left fingers. The result showed the local relation between TM and CAM wasn't strictly symmetric. In Experiment II, 60 children ranging in age from five to seven were required to consciously control their contralateral finger movements while they played TM. Following three conditions were provided; 1) The free condition with no control, 2) the inhibitory condition with conscious inhibition of CAM, and 3) the imitative condition with a typical CAM pattern. Findings were that, though all children could inhibit CAM consciously, the five year-olds couldn't. Furthermore, TM performance improved in the lower performance group, but it deteriorated in the higher group in association with the contralateral control. These results suggest that there is a cooperative and reciprocal relationship between TM and the contralateral finger movements. PMID- 2250415 TI - [Investigation of the concurrent validity of a new personality inventory: construction of a new personality inventory by means of factor analysis based on promax rotation (II)]. AB - The purpose of the present study is to investigate the concurrent validity of a new type of personality inventory (NPI) which has been constructed by the present authors. For this purpose, we conducted three kinds of studies. The first one was to find the relationship of the 13 scales of the NPI with the 12 scales of YG personality inventory. Factor analysis and canonical correlation analysis were employed for the study. It was found that the NPI measured relatively wider area of personality traits as compared with the YG inventory. The second and the third studies were concerned with the concurrent validity of the NPI. The inventory was applied to both six hundred company workers and two hundred university students, and they were classified into adjusted and maladjusted groups respectively according to their responses to a questionnaire aimed at measuring the adaptability to jobs or to majors. Results showed that the 13 scales of the NPI had a strong predictive power in the sense of the concurrent validity. Further studies are needed in order to measure the predictive validity of all the scales of the present personality inventory. PMID- 2250416 TI - [The effects of impolite computer messages on workers]. AB - The purpose of this study was to clarify the effects of computer messages of varying degrees of politeness on subjects' task performance, mental state, and attitude toward computers. The task of subjects in the experiment was to type characters into the computer. When subjects made an input mistake or exceeded the time-limit, or required aid (used the HELP key), a message was given by the computer to which subjects had to reply by pressing either the "Shut up!" button or the "I am sorry" button. Before and after the experiment subjects were required to answer a questionnaire concerned with their image and attitude toward computers and the degree to which the task of typing is unpleasant. The main results were: 1) Subjects who received impolite messages felt that the message was unfriendly, but felt less unpleasantness in typing than subjects who received no message. Subjects became aggressive when impolite message were given repeatedly. 2) Subjects who received impolite messages showed positive attitude change toward computers despite the impolite messages. PMID- 2250417 TI - [Individual differences in encoding and decoding of nonverbal expressions]. AB - The purpose of this experiment was to examine correlations among encoding ability, decoding ability, and individual differences. Thirty undergraduates were measured on the CP110 (short version of California Personality Inventory), Y-G Personality Inventory, and assessed for their ability to encode and decode facial and vocal expressions depicting six different emotions. The main findings were as follows: (a) encoding scores were positively correlated with both CP110 and Y-G; (b) decoding score was correlated with CP110 and negatively correlated with Y-G; (c) there was no correlation between encoding and decoding score on vocal expression or facial expression; and (d) there was no sex difference. PMID- 2250418 TI - [Expectancies of foreign exchange senior high school students towards advisors in Japan]. AB - To contribute to the improvement of conditions for receiving exchange students from abroad, the present study was conducted to clarify the expectancies of such students towards their advisors and to explore possible changes in expectancy as the students gained greater familiarity with the Japanese culture. The types of response the exchange students expected from the advisors were classified into 12 categories including giving advice, acting on behalf, encouragement to be independent, listening, probing, interpretation, value judgment, empathy, clarification, support, confrontation, and others based on Ivey's (1980) microskills classification. An almost identical questionnaire was administered twice to 288 senior high school exchange students from 20 countries upon their arrival in Japan and ten months subsequent to their arrival. The results may be summarized as follows: (1) Although the subjects expected the same responding type from their advisors in Japan as they did from their parents, they were rather dependent on the advisors on their arrival; (2) as time passed and the subjects became more familiar with the Japanese culture, their expectancies towards the advisors became more similar to those in their home countries; and, (3) the longer the subjects stayed in Japan, the more independent the responding type they expected from the advisors. PMID- 2250419 TI - [A comparative study of individuals' responses to formative and declining groups]. AB - Using 40 college students as subjects, this experiment was conducted to investigate differences in the influence exerted by formative groups and declining groups of the same size. No significant differences between formative and declining groups were found at the behavioural level, especially with respect to conformity rates. However, significant differences were found between the two groups at internal levels, especially with respect to the confidence exhibited in subjects' responses and the evaluation of group opinions. In formative groups, the confidence of conformers in the group increased but non-conformers showed no change. In declining groups, the confidence of non-conformers increased but conformers showed no change. Moreover, only the conformers continued to support group opinions after the groups broke down, evaluating the group opinions highly in private. The results suggested in general that individuals are influenced by group changes and that they select their own responses by anticipating changes likely to occur in the group. PMID- 2250420 TI - [Some differences between the visual and auditory memories in the short-term memory]. AB - In order to clarify the differences between the visual and the auditory memories and the interference effect between them, a paired presentation method was developed. In this method, the subject under the experimental condition memorized two independent sequences of random digits, which were presented simultaneously digit by digit, the digits of the one sequence being presented visually and the digits of the other auditorily. After the presentation, subjects were asked to recall first either the visual or the auditory digit sequence, and then the other sequence. The subject under the control condition, on the other hand, memorized one sequence of random digits which were presented either visually or auditorily, and after recalling them memorized another sequence of random digits presented in the other modality. The results can be summarized as follows. (1) Under the experimental as well as under the control conditions, the recency effect appeared in the auditory memory task, but it did not in the visual memory task. (2) The performance for visual by presented digits under the experimental condition was lower than that under the control condition, whereas the performance for auditorily presented digits under the former was equal to that under the latter. The results presented might suggest that: (1) there are independent visual and auditory memories in the short-term memory; and (2) the memorizing of the auditory materials interferes with the memorizing of the visual one, but the latter does not interfere with the former. PMID- 2250421 TI - [The influence of perceived mother model attitudes on children's aggressive or prosocial behavior]. AB - The present experiment was to examine the influence of perceived attitudes of mother models on preschool children's aggressive or prosocial behavior. Based on the score of CCP (children's cognition of parents) Test, sixty four-year-olds were selected and then modeling sessions were administered to them. Their mothers and kindergarten teachers were asked to answer a questionnaire on aggression and altruism of children in daily life situations. Mothers were also required to make self-ratings on their aggression, altruism and rearing attitudes. The following results were obtained. Boys who perceived being rejected by their mothers displayed less imitative aggressive behaviors than other boys and they showed significantly more extrapunitive responses in the P-F Study. No relationships were found between children's modeling behaviors and their aggression or altruism. Children's aggression at kindergarten correlated positively with their aggression at home and with their mother's aggression. It was noteworthy that girl's altruism at kindergarten correlated positively with their mother's rejection, control, and aggression. PMID- 2250422 TI - [Effects of elaboration on retrieval of words in incidental memory]. AB - The present study was carried out to investigate the mechanism of retrieval of words in incidental memory. Thirty college students were asked to generate free associates to each target word followed by unexpected free recall and recognition tests. In the free recall test, subjects were instructed to recall both targets and generated associates. The probability of targets which elicited more associates correctly recalled was higher than that of those which did less when their associates previously recalled. The above result was interpreted as showing that the more target words had retrieval route from the generated associates the more they were recalled. False recognition score as an index of between-item elaboration was higher to an associate elicited by three targets than by two or one. No clear effects of between-item elaboration were observed for free recall performance of targets. These results were discussed in term of between-item and within-item elaboration. PMID- 2250423 TI - [Effects of body-satisfaction on social anxiety and self-disclosing behavior in adolescence]. AB - The present study investigated effects of body-satisfaction on social anxiety and self-disclosing behavior, focusing on the relationship between body and self in adolescence. Thirty-six male and thirty-six female undergraduates talked with an interviewer of the same-sex or opposite-sex. Their interactions were video-taped. The following results were obtained: (1) body-satisfaction level had an effect on social anxiety and on the style of self-disclosing behavior, but not on the contents of disclosure, (2) the high body-satisfaction group was shy and passive with an interviewer of the opposite-sex, and this seemed to be common among late adolescents, (3) the low body-satisfaction group was anxious, shy, tense, and passive with an interviewer of the same-sex, (4) the low body-satisfaction group was both tense and active with an interviewer of the opposite-sex (these results suggest that a relationship exists between body-satisfaction and gender identity confusion), (5) body-satisfaction level had no effect on interpersonal distance. PMID- 2250424 TI - [A study of seat-taking in seminar classes: data analysis of three seminar classes in a women's university]. AB - The purpose of this study was to examine the conditions under which human territoriality (self/other boundary-regulation mechanism) appears in seat-taking behavior. Seat-taking in a social psychology seminar class of twelve students at a women's university was observed during the 1983, 1984 and 1985 academic years by female part-time lecturer (the author herself). At the beginning of each class, the lecturer drew the figure of the students' seating arrangement at a rectangular table, while calling each student's name. Questionnaires were also administered to the students at the end of the observation in the period 1983 and 1985 academic years. The results obtained were: 1) each student was more attached to one seating area and seating side than the others, 2) this fact reflected her seating preference to some extent, 3) no student monopolize the special seats to which she was most attached, 4) extra spaces were left between the lecturer's and the student's seat. The third finding was considered to be due to homogeneity of the student with respect to major, grade and sex and their temporal relationships within the seminar group. Also the fourth result was due to the status difference between the lecturer and the students, which led to the recognition that the seating places were mutually exclusive for both sides of them. PMID- 2250425 TI - [Images of life, death, word and body in adolescence]. AB - Using single-adjective semantic differential scales, images of life, death, word and body were examined in 176 male and 208 female university students. The results were as follows: (1) Factor analysis of scales were carried out concept by concept. Two factors, the positive image and the negative image, were extracted for all concepts. (2) The concepts of life and death showed a concept scale interaction, whereas the factorial structures of the concepts of word and body were very similar. (3) Factor scores indicated that females have a more positive image of life than males, and that males have a more negative image of death and a more positive image of body than females. There was no sex difference in the image of word. (4) The positions of concepts in semantic space indicated that self-image and life image are very similar in females. PMID- 2250426 TI - [The effect of the instantiating information on association between categories and instances]. AB - Two experiments were carried out to make clear the mechanism of inferences and the representation of semantic categories with the instantiating information. In Experiment 1, verification times of instantiating-context-dependent category membership were measured for 24 graduate and undergraduate students. Verification times in RT (related true instance) condition were faster than those in UT (unrelated true instance). But those in RF (related false instance) condition were equal to those in UF (unrelated false instance). In verifying the context dependent category, not forward association inferences from categories with the instantiating information to instance but backward association inferences from instances to instantiating contexts occurred. The results suggested that there weren't the instantiated representations of categories. In Experiment 2, categories with the instantiating information and instances were used as the predicate term in deductive reasoning. Judgements of validity and their reaction times under time pressure were measured for 24 graduate and undergraduate students. Percentages of valid responses were high in valid figure, and reaction times in universal negative proposition were longer. It was concluded that, when the tacit premises are introduced, backward association inferences are much more used than forward association inferences. PMID- 2250427 TI - [Interpersonal anxiety and the self-others cognitive system: a study of the Self identity System]. AB - This study examined the self-others cognitive systems of anthropophobia in terms of the (an) object relationship disorder. The Self-identity Systems of 259 students were measured to clarify visually the relationship between self and others in terms of self and others cognition and interpersonal anxiety. Cluster analysis and principal components analysis of the Self-identity Systems led to the appearance of five Self-identity System types for each sex. Low anxiety level subjects tended more toward the "self convergence type" while high anxiety subjects tended more toward the "self alienation type". These results suggest that disorder in the self-others cognitive system and the problem of self identity relate to anthropophobia. PMID- 2250428 TI - [Renal function after aortic reconstruction for aortic dissection: special reference to the renal blood flow from false lumen]. AB - Relationships between preoperative renal blood flow and postoperative renal dysfunction after aortic reconstruction for aortic dissection of DeBakey I and IIIb type were discussed. The incidence of renal dysfunction after surgery was not so high and renal failure was transient. Renal dysfunction occurred in the cases with true lumen oppressed by false lumen at chronic stage. Sometimes, abnormal findings were showed in CT scanning and/or renogram even in serum creatinine or BUN value was normal. In conclusion, our data showed justification of anastomosis of distal artificial graft to true lumen in acute stage. But in chronic stage, it is very important in point of selection of operative method to recognize how renal blood flow was preserved and to know the location and size of reentry before surgery. PMID- 2250429 TI - [Surgical treatment of bullous emphysema using Gore-Tex sheet]. AB - Surgical treatment for bullous emphysema using Gore-Tex sheet and mechanical stapler is reported. The techniques were followed in a Juetnner's report: Small cut is made at the center of a 10 cm square of a Gore-Tex sheet, through which the area of bullous lung planned for resection is tented out with a lung forceps. A stapling instrument charged with a 4.8 mm clips is placed over the sheet around the suture line, and closed over both sheet and lung parenchyma. The excess sheet is removed after resection of the bullous lung. Five cases of bullous emphysema with a history of pneumothorax were successfully treated by the above method. Air leakage disappeared on the first postoperative day at latest. We assume Gore-Tex sheet, although a non-absorbable material, is in use as well as polydioxanone ribbon for prevention of air leakage in surgical cases of bullous emphysema. PMID- 2250430 TI - [Long-term results of total correction of tetralogy of Fallot less than 2 years old]. AB - Between April 1972 and March 1979, eighteen total correction for tetralogy of Fallot less than 2 years old were performed with a mortality rate of 11.1%. The valved patch made of autologous pericardium was utilized for right ventricular outflow reconstruction in 12 of 16 survivors. Late (from 10 to 17 postoperative year) results of the all survivors were studied on functional and clinical status, hemodynamics and cardiac functions, and also, were compared with that of the patients above 2 years of age. All of them were in NYHA class I with no physical exercise limitation. Chest X-ray showed nearly normal CTR of 51.7%. ECG showed complete or incomplete RBBB in 14 patients and LAD in 3 of them, whereas no ventricular arrhythmia. Cardiac catheterization and cineangiography revealed that they had quite satisfactory hemodynamics and cardiac functions despite their moderate pulmonary regurgitation. In comparison with the older patient group, this younger one had a tendency to take superior results in all parameters of cardiac functions and clinical status. These excellent long term results seem to come from their young and less degenerative myocardium at the time of surgery. PMID- 2250431 TI - [Long-term results of coronary artery bypass grafting: comparison of angiographic evaluation of internal thoracic artery and saphenous vein grafts]. AB - The long term (10 to 15 years) results of coronary artery bypass grafting (CABG) were studied in 20 patients. The duration of follow-up was ranged from 130 to 170 months with mean 146.4 months. Ten out of 20 patients underwent coronary angiography (CAG), which disclosed that the late patency of saphenous vein (SV) grafts was 68.8% (11/16), but 54.5% (6/11) of patent SV grafts showed atherosclerotic changes such as irregularity and localized narrowing. On the other hand, internal thoracic artery (ITA) grafts were all patent without any atherosclerotic luminal changes. We recognized that ITA grafts were superior to SV grafts from an angiographic standpoint of view in the long term in Japan. PMID- 2250433 TI - [Measurement of myocardial temperature with infrared radio-thermometer in cardiovascular surgery]. AB - We used an infrared radio-thermometer for measurement of myocardial temperature in cardiovascular surgery and a high correlation was observed when it was compared with a contact thermometer. This thermometer is characterized by the fact that it can be used in a non-contact remote-control manner either in a moving body or in a dark location. It is expected that this thermometer will be increasingly used in the clinical area in the future. PMID- 2250432 TI - [Surgical treatment of hypoplastic left heart syndrome: a successful case report]. AB - A successful case of Norwood operation for a 5-day-old infant with hypoplastic left heart syndrome is reported. Norwood procedure and central shunting with a 4 mm PTFE tube was performed. Cerebral and coronary artery were perfused independently during reconstruction of aorta in order to shorten the time of circulatory arrest. Post operative UCG documented un-obstructive systemic output from the right ventricle, well regulated pulmonary arterial blood flow and widely patent interatrial communication. This baby was discharged the hospital 66 days after surgery. He has been clinically well for six month after the operation. PMID- 2250434 TI - [Abrasion perforation of two intra-aortic balloons]. AB - We report two patients whose intra-aortic balloons exhibited delayed perforation caused by prolonged contact of the balloon against calcific atheromatous plaque. Perforation was diagnosed by the presence of blood in the tube connecting the balloon. Leak detection systems were useless to diagnose this complication. We believe that the balloon immediately should be removed at the presence of blood in the tube. PMID- 2250435 TI - [Two cases of perioperative coronary vasospasm following ASD closure and OMC]. AB - Two cases of perioperative coronary spasm following ASD closure and OMC are reported. A 36-year-old female had been diagnosed of vasospastic angina and another 47-year-old female patient was diagnosed of effort angina for 99% stenosis of the right ventricular branch preoperatively. Both patients suffered from coronary vasospastic attack and ventricular fibrillation several times within 17 hours postoperatively. Although the coronary dissolution was obtained finally following aggressive cardiac massage, administration of spasmolytic agents, such as NTG, lidocaine, DBcAMP and the start of IABP, the resolution was stormy due to the hemodynamic derangement. To prevent the coronary spastic episode, it is suggested, for patients of possible coronary spasm, to avoid arousal stimulation and to administer spasmolytic agents prophylactically within the first postoperative day. PMID- 2250437 TI - [A surgical case of aortic regurgitation with Behcet disease]. AB - A case of Behcet disease associated with aortic valve regurgitation treated with aortic valve replacement is reported. The patient was treated successfully with special surgical techniques for prevention of post operative paravalvular leakage and occurrence of pseudo aneurysm because the patient was under long-term steroid therapy for Behcet disease. PMID- 2250436 TI - [Surgical treatment of aortic root aneurysm associating with infectious endocarditis]. AB - From 1979 to 1989, aortic root aneurysms were encountered in 6 of the 30 patients who underwent surgical treatment for infectious endocarditis. Four patients underwent aortic valve replacement and direct or patch closure of the orifice of aortic root aneurysm. In additional 2 patients with infected aneurysm of right coronary sinus of Valsalva rupturing into the right ventricle, the aneurysm and infected tissue in the right ventricular outflow tract were completely resected and the defect of aortic sinus and VSD were closed with double Teflon fabric patches. All patients survived postoperatively, however, one patients died 1.5 months after the operation probably due to rupture of mycotic aneurysm of cerebral artery. Another late death seemed to be concerned with recurrent aortic root aneurysm, in which case direct closure of aneurysm had been performed. We believe that even if the aneurysm seems to be small, its orifice should be closed with the use of a fabric patch to prevent recurrent aneurysm formation. PMID- 2250438 TI - [A case of chronic traumatic aneurysm of the descending thoracic aorta with the aberrant right subclavian artery]. AB - A 59-year-old man had developed gradual prominence of the aortic knob in a chest X-ray film after a blunt chest trauma. Two and a half years after trauma, an angiogram revealed the aberrant right subclavian artery and a saccular aneurysm at the thoracic descending aorta just distal to it. It was treated with patch closure of the entrance of the aneurysm under a temporary bypass. Pathological findings were tearing off of a medial layer of the aorta. Postoperative course of this case was excellent. It must be noticed that the traumatic thoracic aortic aneurysm had a high possibility of rupture even in the chronic stage. PMID- 2250439 TI - [Surgical treatment of syphilitic ascending aortic aneurysm: a case report]. AB - A 67-year-old man with positive serum reaction for syphilis had been followed by cardiologist for his moderate-sized saccular ascending aortic aneurysm and small sized abdominal aortic aneurysm. Because of his transient ischemic attack probably secondary to the thrombo-embolism of the aneurysm and rapid growing of its size, surgical treatment was recommended. Resection of the saccular aneurysm with patch plasty of the ascending aorta was performed under the cardiopulmonary bypass associated with right side cerebral perfusion. At the time of operation, the mildly dilated ascending aorta and arch with multiple intimal ulceration were noted. Although his postoperative hemodynamic condition was stable, he suffered from multiple cerebral infarction, probably due to embolism migrated from the fragile aortic intima. His neurological condition was improved promptly, trivial hemi-paralysis was remained. The specimen of resected aneurysmal wall revealed syphilitic changes microscopically. We concluded that the extent of the aortic replacement with prosthetic graft should be deceived not only with its external appearance, but also with the changes of its inside. PMID- 2250440 TI - [Experience of surgical therapy of pyothorax in the pleural fistula of the bronchi and esophagus due to esophageal cancer]. AB - The esophagectomy and total left pneumonectomy were carried out in a 53-year-old male who had developed pyothorax in the pleural fistula of the bronchi and esophagus due to esophageal cancer, and then reconstruction of the esophagus by route of the anterior thoracic wall was performed using stomach tube biphasically. The postoperative course was favorable, and oral intake was possible, and his physical condition recovered as the patient could repeat stopping out from hospital while he died by pneumonia after 7 months. The remote metastasis or metastasis to the mediastinal lymph-node were not noted by autopsy. It is considered that there are cases having indication for active resection among A3-esophageal cancers. PMID- 2250441 TI - [A case report of coronary artery bypass surgery (3-SVG) in 80-year-old woman with acute respiratory failure]. AB - A successful operation for a patient of unstable angina with hypoxia is reported. A 80-year-old woman was admitted with severe chest oppression. The selective coronary angiogram revealed 3-vessel disease. Symptoms were uncontrolled by medical therapy. Aorto-coronary bypass surgery (with 3-saphenous vein grafts) was followed by excellent post-operative course. The patient has been asymptomatic for more than 1 year after operation. PMID- 2250442 TI - [A case of right atrial myxoma, originating from the eustachian valve]. AB - We describe a rate of right atrial myxoma, originating from the Eustachian valve, which entered and occupied the right ventricle during the diastolic phase. A 65 year-old woman was admitted with symptoms of palpitation and tachycardiac attack. The condition was diagnosed by echocardiogram and an emergency operation performed. The tumor was removed with the endocardium around 1 cm2 at its stalk in order to prevent recurrence of tumor. No recurrence has developed during the subsequent 2 years 4 months. PMID- 2250443 TI - [A case of thoracoabdominal aortic aneurysm ruptured into the right extrapleural cavity]. AB - A 63-year-old man of thoracoabdominal aortic aneurysm was transferred to our department. Thoracic and abdominal enhanced CT scan revealed a Crawford's type I A thoracoabdominal aortic aneurysm ruptured into the right extrapleural and retroperitoneal spaces. Without any more additional examination, graft replacement and reconstruction of a lower intercostal artery were performed with an aid of femoro-femoral bypass. Although the postoperative course was complicated by hypertension, hypoventilation and liver dysfunction, the patient recovered from the operation and 10 months later he is leading an almost normal life. Since emergency operation of thoracoabdominal aneurysm is the most courageous challenge because of the difficulties of exposure and visceral organ protection against ischemic, there have been only nine cases with successful surgery in Japan. Now we actively reconstruct lower intercostal and lumbar arteries to prevent spinal cord ischemia without ESCP monitoring in emergency cases. PMID- 2250444 TI - [Cor triatriatum associated with coarctation of the aorta and VSD]. AB - A case of cor triatriatum associated with coarctation of the aorta (CoA) and VSD is reported. A 4-month-old boy underwent subclavian flap aortoplasty and ligation of PDA with the diagnosis of CoA and VSD. At the age of 1 year and 2 months, echocardiography revealed an abnormal subdividing membrane in the left atrium. Under the definite diagnosis of cor triatriatum (Lucas & Schmidt type I B1) and VSD, complete removal of the abnormal septum, patch closure of ASD and VSD was performed with the aid of cardiopulmonary bypass, blood cardioplegia and topical cardiac cooling. Postoperative course was uneventful and the patient was discharged from the hospital on the 38th postoperative day. An association of cor triatriatum, VSD, and coarctation of the aorta is very rare, and to our knowledge, the case presented here seems to be the first report of successful total correction by a staged approach in the literature. PMID- 2250445 TI - [An aged case of coronary-aorta bypass grafting surgery (CABG) with severe chronic obstructive pulmonary disease]. AB - This paper reports CABG which was successfully performed on a male patient of 70 year-old with severe chronic obstructive pulmonary disease (FEV1.0% 43%) and diabetes mellitus. The patient necessitated reintubation because of hypercapnea on 18 POD in spite of bronchodilator and physical therapies. Long respiratory care was continued after tracheotomy, and finally he could wean from the mechanical respiratory care utilizing acetazolamide (carbonic anhydrase inhibitor) on 59 POD. PMID- 2250446 TI - [The unification of Europe and its consequences for Swiss nursing personnel. Swiss nurses have nothing to fear. Interview by Fred Arm]. PMID- 2250447 TI - [Foreign nurses and registration at the Swiss Nursing Registry. Very diverse starting problems]. PMID- 2250448 TI - [Introductory concepts for foreign nursing personnel. Getting rid of anxieties and prejudices]. PMID- 2250449 TI - [The status of nursing in Great Britain. Radical reforms lead to nursing shortages]. PMID- 2250450 TI - [After 2 years in Switzerland back to Germany. Nursing is shortchanged]. PMID- 2250451 TI - [A Swiss nurse in Stockholm. We support the feeling of wellbeing]. PMID- 2250452 TI - [A German nurse after 10 years in Switzerland. Turned useless for German nursing?]. PMID- 2250453 TI - [2 Finnish psychiatric nurses in Switzerland. "I am missing here the personal supervision". Interview by Kaarina Karlstedt]. PMID- 2250454 TI - [A visit with Polish nurses. Great achievement with a minimum of means]. PMID- 2250455 TI - [Nurses--a potential in AIDS control]. PMID- 2250456 TI - [Women have a key role in the campaign against AIDS]. PMID- 2250457 TI - [To be a nurse in Switzerland: a chance]. PMID- 2250458 TI - [I live in France, I work in Geneva...]. PMID- 2250459 TI - [A reception program for our new personnel. Ask, and we shall answer!]. PMID- 2250460 TI - ["They need us here"]. PMID- 2250461 TI - [Attending the dying in Haitian and Swiss rural areas. A revealer of cultural values]. PMID- 2250462 TI - [How is the foreign personnel in the Tessin getting along?]. PMID- 2250463 TI - [Addictive diseases in the nursing home]. PMID- 2250464 TI - [Alcoholism from the viewpoint of a factory physician]. PMID- 2250465 TI - [Etiology, clinical aspects and possible prevention in sudden infant death (SIDS)]. PMID- 2250466 TI - [Dermatological aspects of incontinence]. PMID- 2250467 TI - [More continuing education]. PMID- 2250468 TI - [Headache--essential points and classification]. PMID- 2250469 TI - [Supervision for hospital nursing personnel]. PMID- 2250470 TI - [Human rights and pain]. PMID- 2250471 TI - Recurrence of resected esophagogastric adenocarcinoma: results of re-resection. AB - Isolated local recurrence following potentially curative resection for carcinoma of the esophagus or esophagogastric junction does not necessarily imply pending systemic disease and early demise. While radiation alone or in combination with chemotherapy is standard treatment for such patients, resection is another available option. Resection may also be a consideration should localized disease persist after non-operative therapy in the absence of metastases. A 5 year retrospective review was performed examining 204 resections performed prior to 1989. Only 5 patients underwent resection of locally recurrent esophagogastric (EG) adenocarcinoma during this period. No squamous carcinoma recurrences were resected. One patient is well 15 months later while another died at 18 months of other causes without recurrence. Recurrence after re-resection occurred at 8, 11, and 24 months in the 3 other patients. Although there were no postoperative deaths, major complications occurred in 4 patients. All 5 patients swallowed normally after operation. PMID- 2250472 TI - Cryoprobe as a "handle" for resection of metastatic liver tumors. AB - Resection of metastatic liver tumors can be a difficult and risky procedure. Using a cryoprobe as a "handle" can greatly facilitate resection by providing a taut surface for transection and improving visualization of ductal and vascular structures. In addition, this technique may decrease the risk of contaminating surrounding tissues with cancer cells, and may inhibit tumor recurrence within the margins of resection. PMID- 2250473 TI - Extended neck dissection. AB - From the time Crile described radical neck dissection in 1906, this surgical procedure became popular in the management of metastatic cancer in the neck. Over the past two decades, the modified neck dissection has been effectively utilized for conservation of function and cosmesis while achieving the same oncologic goals. However, there are several instances where the above standard procedures are not adequate for resection of malignant tumors. Although there is a definite trend toward conservation procedures, extended neck dissection is often necessary especially in patients with N2 and N3 disease. Apart from the standard structures removed in radical neck dissection, the other structures removed in extended neck dissection include skin, the digastric muscle, hypoglossal nerve, vagus nerve, sympathetic chain, ramus mandibularis, carotid artery, tracheo-esophageal nodes, etc. Over the past seven years, we have performed 40 extended neck dissections. All the patients had N2 or N3 disease in the neck. Nine patients had unknown primaries. Thirteen patients had their primary tumors in the oral cavity and 11 in the laryngopharynx. Five patients had primary tumor in the salivary glands and two patients had metastatic melanoma. Patients who underwent extensive skin excision had pectoralis myocutaneous flap reconstruction. All patients received postoperative radiation therapy. One patient died of cardiac problems 4 weeks after operation. Local control was achieved in 70%. The most difficult region for local control was the disease behind the mastoid process, and the most difficult problems were patients with involvement of the subdermal lymphatics. Our data suggests that there are definite situations where extended neck dissection is indicated with satisfactory local control of the nodal disease. PMID- 2250475 TI - Surgical wound infection and cancer among the elderly: a case control study. AB - Surgical wound infection occurs in fewer than 5% of operations. Nevertheless, it represents the second most common type of hospital-acquired infection and results in increased morbidity and mortality. As with all nosocomial infections, the rate of surgical wound infection increases with age. Patients over 65 years of age run an approximately 15% risk of surgical wound infection. Two-thirds of patients with invasive cancer other than non-melanotic skin cancer are aged 65 years and over. Over half of them are treated surgically for their cancer. Cancer and other chronic diseases have been cited as possible causes of the increased risk of nosocomial infection among the elderly. Using the Foothills Hospital Wound Study Data Base as the sampling frame, we conducted a case-control study of surgical wound infection and cancer among the elderly. Cancer was found not to be a risk factor for surgical wound infection. The results are discussed in relation to the role of immunity in both disorders. PMID- 2250474 TI - Gamma-detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX-1 colon xenografts. AB - Nude mice bearing CX-1 colon tumors were injected with 50 microCi 125I-labeled monoclonal antibody (MAb) B72.3. Radioactivity in tumors was studied with the gamma detecting probe (GDP) on days 1, 3, 7, and 10 after MAb injection. On each day, two mice were sacrificed and sections were examined with autoradiography (ARG), immunoperoxidase methods (IMP), and routine stains. Mean probe counts showed increasing tumor to background ratios and ARG demonstrated a progressive increase in radionuclide in the tumors. The distribution of 125I was primarily around the vascular spaces on day 1, but by day 3 and progressively it appeared in tumor gland lumina and necrotic areas. A regional correlation was shown between radionuclide in vascular spaces and its sequestration in tumor elements. PMID- 2250476 TI - Carcinoid tumors. AB - The authors carried out a retrospective study of 32 patients (23 M, 9 F) with carcinoid tumors who were diagnosed and treated at Harlem Hospital Center, New York, from 1967 to 1988. All the patients were black and the commonest sites were the ileum (28.1%), rectosigmoid and rectum (21.9%), and the appendix and lung (15.6% each). Metastasis correlated with site, size, and depth of the primary tumor and occurred in 12 patients (38%), most frequently to the regional lymph nodes and liver. Carcinoid syndrome developed in 12.5% (3 F, 1 M). Surgical resection for cure or palliation was the mainstay of treatment. Overall 5 year survival rate was 66%, and for those with metastases was 0%. The poorer survival rates are probably related to the socioeconomic status of our patient population. The only observed racial difference compared to other series is the preponderance of males, and the disproportionately higher ratio of females with the carcinoid syndrome. PMID- 2250477 TI - Symptomatic pericardial effusion in breast cancer patients: the role of fluid cytology. AB - Clinical and cytologic findings in 21 breast cancer patients with symptomatic pericardial effusion are presented. The etiology of the pericardial effusion was definitely malignant, by cytology/histology in 13 patients (62%), and suspected malignant by cytology in 2 patients (9%). One patient (5%) with definitely nonmalignant pericardial effusion by cytology was found to be histologically positive at autopsy. In 5 patients (24%) there was no histological/cytological evidence of malignancy; radiation pericarditis could be the etiology in 4 of these 5 patients. The median time from the diagnosis of breast cancer to the development of symptomatic pericardial effusion was 60 months (range: 1-219 months). Ten patients developed cardiac tamponade; they were treated by either pericardiocentesis or pericardiectomy. The mean survival of patients with negative cytology/histology was 12 months; patients with suspicious cytology had a mean survival of 9 months; patients with malignant effusion, treated by pericardiectomy, had a mean survival of 22.3 months, while patients with malignant pericardial effusion, who were not subjected to surgery, had a mean survival of 4.7 months, only. It is concluded that the etiology of symptomatic pericardial effusion in breast cancer patients is not always malignant, which emphasizes the role of fluid cytology in establishing definite diagnosis. The survival probability is a function of the extent of extracardiac disease; among patients with malignant pericardial effusion those selected for pericardiectomy have a longer than average survival. PMID- 2250478 TI - Hemicorporectomy: a collective review. AB - Hemicorporectomy or translumbar amputation has been described as the most revolutionary of all operative procedures. Frederick E. Kredel, who first voiced the concept of the operation in 1950, referred to it as halfectomy. Demonstration of his cadaver studies established the feasibility of the operation. Amputation is effected through the lower lumbar area of the body. Necessary life functions are preserved in the upper torso. Kredel envisioned hemicorporectomy as a curative operation for locally advanced cancer, limited to the pelvis, not encompassable by standard operative intervention. Additional indications are intractable decubitus ulcers with malignant change, particularly in paraplegics; pelvic organs, and bone infection with nonhealing fistulae; and crushing trauma to the pelvis. The first hemicorporectomy operation was reported in 1960. Thirty four operations have been recorded in the world literature. Two heretofore unreported cases are added, raising the total to 36. Review of these 36 cases confirms the conviction that hemicorporectomy is a humane and ethical alternative to the suffering encumbered by advancing, painful, malodorous malignant disease not treatable by conventional means. While cure rates are not substantial, the best results are reported in paraplegics with intractable decubitus ulcers with or without malignancy. Rehabilitation is prolonged and costly. Most survivors have been restored to preoperative occupations or other gainful employment. PMID- 2250479 TI - The use of interferon alpha-C in patients with metastatic renal cell carcinoma arising in a congenital solitary kidney. AB - Three cases of renal cell carcinoma in a congenital solitary kidney are presented. Treatment with recombinant interferon alpha-C was administered in two cases. A subjective response occurred in one case. The literature is reviewed with respect to treatment options and prognostic factors. PMID- 2250480 TI - The lymphatic edema safety factor: the role of edema dependent lymphatic factors (EDLF) PMID- 2250481 TI - Lymphatics, intraepithelial lymphocytes and endometrial lymphoid tissues in the rabbit uterus: an electron microscopic and immunohistological study. AB - Rabbit uterine intraepithelial lymphocytes, endometrial lymphoid aggregates and lymphatic capillaries were examined electron-microscopically and immunohistochemically at well-defined intervals after the injection of human chorionic gonadotropin (hCG). Lymphatic capillaries originated near the bases of the glands in the uterine cervix and in the border zone between the lamina propria mucosae and myometrium in the uterine body. The lymphatic capillaries were maximally dilated, and their endothelial cells were thinnest 8 hours after hCG injection. Patent junctions between the adjacent endothelial cells of lymphatics in the uterine body were observed in good accordance with the appearance of stromal edema and lymphatic dilatation. The numbers of intraepithelial lymphocytes and macrophages changed cyclically after the induction of ovulation. They were highest 11 hours after hCG injection when lymphocytes were seen occasionally in the lumens of lymphatics located in the lamina propria mucosae of the uterine body. Most of the intraepithelial and interstitial lymphocytes were cells labeled with T cell serum but some were labeled with IgA serum and were occasionally seen beneath the epithelium. Lymphoid aggregates were uniformly present in the stratum basalis and consisted of lymphocytes and macrophages. They had no germinal centers, surrounding lymphatics or high endothelial venules (HEV). The results suggest that lymphatic capillaries are the main route for the removal of edema fluid and for migratory lymphoid cells in the rabbit uterus. PMID- 2250482 TI - Histological framework of lymphatic vasa vasorum of major arteries: an experimental study. AB - We investigated the histological framework of lymphatic vasa vasorum of major arteries in the rabbit and guinea pig combining the "natural filling method" with light and transmission electron microscopy. An absorbing adventitial lymphatic network consisting of large and sparsely distributed vessels with capillary structure occupied a more external arterial wall position than blood capillaries. The latter were smaller, more numerous, densely distributed, and located closer to the arterial lumen at the media-adventitial border. Periarterial lymphatics (with the structure of absorbing lymph vessels) encircled the wall of the major arteries and formed a rich and irregular plexus. The topography and anatomic structure of these absorbing lymph vessels suggest that lymphatic drainage plays a significant role in large arterial wall homeostasis. PMID- 2250483 TI - Diameters of lymphatic capillaries in patients with different forms of primary lymphedema. AB - Fluorescence microlymphography was performed near the medial ankle in 12 healthy controls, 12 patients with congenital and 12 with sporadic lymphedema of the lower extremities. Diameters of lymphatic capillaries were determined on the videoscreen by playback of the tape recordings using a morphometric technique. In the patients with congenital disease (Nonne-Milroy) aplasia of microlymphatics was diagnosed in 8 instances, ectasia in 4. Patients with sporadic lymphedema and manifestation after puberty exhibited initial lymphatics of normal caliber. In controls mean capillary diameter was 56.3 +/- 9.0 microns, in congenital disease with ectasia 99.3 +/- 9.0 microns (difference significant at the p less than 0.005 level) and in the sporadic form 49.7 +/- 7.7 microns. Congenital lymphedema may be subdivided into a form with aplastic and ectatic microvessels which possibly show different responses to therapy. PMID- 2250484 TI - The effect of anesthesia and surgery on diaphragmatic lymph vessel flow after endotoxin in sheep. AB - Increases in diaphragmatic lymph vessel flow (Qdi) may be important in preventing ascites because diaphragmatic lymph vessels drain the peritoneal space. However, lymphatic vessel function may be depressed in anesthetized, open chested animals. To test this hypothesis, we cannulated diaphragmatic lymph vessels in five sheep which were anesthetized with 1-2% halothane. We performed a thoracotomy and cannulated a diaphragmatic lymph vessel in each sheep. Then we infused 0.75-1.0 micrograms/kg of E. coli endotoxin intravenously and we measured Qdi and the lymph protein concentration for 2-4 hrs. The data were compared to previously reported data for five unanesthetized sheep (J. Appl. Physiol. 62:706-710, 1987). At baseline Qdi = 0.8 +/- 0.7 (SD) in the anesthetized sheep and 1.0 +/- 0.8 ml/hr in the unanesthetized sheep. After endotoxin, Qdi increased to 4.5 +/- 3.1 ml/hr in the unanesthetized sheep (p less than 0.05) but Qdi did not change in the anesthetized sheep. However, the lymph protein concentration increased similarly in each group, indicating that endotoxin caused the same degree of injury in each group. Our results indicate that diaphragmatic lymph vessel function is depressed in anesthetized, open chested sheep. PMID- 2250485 TI - Effect of interleukin-2 on microvascular liquid and protein transport in the rat small intestine. AB - Interleukin-2 (IL-2), a glycoprotein lymphokine derived from activated T lymphocytes displays potent anti-cancer properties but its therapeutic use has been limited by generalized tissue swelling. To shed light on the mechanism underlying this potentially life-threatening edematogenic syndrome, recombinant IL-2 or an equal volume of control solution (excipient or 5% dextrose) was administered to 88 adult, male Sprague-Dawley rats. Initially, rats were injected with 50,000 Cetus units (equal to 300,000 I.U.) of IL-2 intraperitoneally, either one-time ("acute" rats) or every eight hours for two or seven days ("chronic" rats). Thereafter, under pentobarbital anesthesia, the main mesenteric lymph duct was isolated, incised, and measurements made of intestinal lymph flow (JV) and the total protein content and protein fractions in lymph (L) and plasma (P) (refractometry and agarose gel electrophoresis, respectively). Final measurements were also carried out after superior mesenteric vein constriction to assess filtration-independent L/P total protein "washdown." After IL-2, JV and protein clearance (JV x L/P) were increased (p less than 0.001) while lymph and plasma total protein content and protein fractionation were unchanged. Protein washdown was also maintained. These data are not only inconsistent with bulk "plasma leak" from damaged capillaries, but in conjunction with previously demonstrated increased cardiac output and reduced systemic vascular resistance after IL-2 administration, the findings favor augmented microvascular surface exchange area from increased capillary perfusion as the primary mechanism underlying increased transcapillary liquid and protein flux. This conclusion conforms to the rapid reversal of edema in patients after cessation of IL-2 therapy. PMID- 2250486 TI - Magnetic resonance assessment of extravascular fluid volume in exercised skeletal muscle. PMID- 2250487 TI - Remission of filarial chyluria after treatment of coexistent conditions. AB - Between April 1965 and March 1984, 659 patients (mean age 52.3 years) with chyluria were encountered (probably from filariasis) and 323 were followed for a mean period of 71.9 months (range 1 to 210 months). Of the 323 patients, chyluria was apparently exacerbated by another condition in 132 (40.8%), and often remitted with effective treatment of the coexistent condition. The findings suggest that chyluria is often accompanied by other physiologic or pathologic processes and treatment of these coexistent conditions should be the initial therapeutic approach. PMID- 2250488 TI - Three strategies to promote cancer screening. How feasible is wide-scale implementation? AB - Many studies have tested the efficacy of intervention strategies for improving physicians' performance of cancer screening tests. Less attention has been paid to the feasibility of strategy implementation. Three important dimensions of feasibility are acceptability to the targeted audience, logistical difficulties, and cost and cost-effectiveness. We assessed the relative feasibility along these dimensions of three intervention strategies shown previously to be efficacious among 62 internal medicine resident physicians. Two strategies, medical record audit with feedback and computerized cancer screening reminders were aimed at physicians directly, and one, patient education, indirectly through their patients. While all three interventions were acceptable to the physicians, implementation of the audit with feedback intervention was logistically more difficult and more costly than either the cancer screening reminders or patient education interventions. The average cost per additional screening test (beyond the number that would have been performed without intervention) was $50.40 for audit with feedback, $18.19 for cancer screening reminders, and $51.20 for patient education. Overall, the cancer screening reminder intervention was the most feasible of the three strategies. PMID- 2250489 TI - Managing physician incentives in managed care. The role of for-profit ownership. AB - The recent rapid growth of HMOs has resulted in a proliferation of contractual arrangements that offer financial incentives to induce primary care doctors to change the way they practice medicine. The impact of these incentives varies with the different incentives and with the environments in which the incentives are implemented. Although financial incentives exist in some form in the great majority of HMOs, there has been no detailed and valid information available on the way these physician incentives are managed or on the characteristics of the standard operating "climate" in which the incentives exist. This study was designed to measure a firm (organizational) characteristic hypothesized to be related to the firm's effort, ability, or desire to make financial incentives work strongly. The characteristic considered is whether the firm is a for-profit or a not-for-profit organization. The goal of this study was to provide a direct test of the relationship between HMO ownership type and the effectiveness of primary care physician incentives. Results of the study indicate that for-profit ownership does enhance the power (or the need) of management to offer effective rewards for parsimonious use of health care resources. PMID- 2250490 TI - The Self-Adapting Focused Review System. Probability sampling of medical records to monitor utilization and quality of care. AB - Medical record review is increasing in importance as the need to identify and monitor utilization and quality of care problems grow. To conserve resources, reviews are usually performed on a subset of cases. If judgment is used to identify subgroups for review, this raises the following questions: How should subgroups be determined, particularly since the locus of problems can change over time? What standard of comparison should be used in interpreting rates of problems found in subgroups? How can population problem rates be estimated from observed subgroup rates? How can the bias be avoided that arises because reviewers know that selected cases are suspected of having problems? How can changes in problem rates over time be interpreted when evaluating intervention programs? Simple random sampling, an alternative to subgroup review, overcomes the problems implied by these questions but is inefficient. The Self-Adapting Focused Review System (SAFRS), introduced and described here, provides an adaptive approach to record selection that is based upon model-weighted probability sampling. It retains the desirable inferential properties of random sampling while allowing reviews to be concentrated on cases currently thought most likely to be problematic. Model development and evaluation are illustrated using hospital data to predict inappropriate admissions. PMID- 2250492 TI - The Duke Health Profile. A 17-item measure of health and dysfunction. AB - The Duke Health Profile (DUKE) is a 17-item generic self-report instrument containing six health measures (physical, mental, social, general, perceived health, and self-esteem), and four dysfunction measures (anxiety, depression, pain, and disability). Items were derived from the 63-item Duke-UNC Health Profile, based upon face validity and item-remainder correlations. The study population included 683 primary care adult patients. Reliability was supported by Cronbach's alphas (0.55 to 0.78) and test-retest correlations (0.30 to 0.78). Convergent and discriminant validity were demonstrated by score correlations between the DUKE and the Sickness Impact Profile, the Tennessee Self-Concept Scale, and the Zung Self-Rating Depression Scale. Clinical validity was supported by differences between the health scores of patients with clinically different health problems. Patients with painful physical problems had a DUKE physical health mean score of 58.1, while patients with only health maintenance problems had a mean score of 83.9 (scale: 0.0 = poorest health and 100.0 = best health). Patients with mental health problems had a DUKE mental health mean score of 49.2, in contrast to 75.7 for patients with painful physical problems and 79.2 for those with health maintenance. The DUKE is presented as a brief technique for measuring health as an outcome of medical intervention and health promotion. PMID- 2250491 TI - Functional status II(R). A measure of child health status. AB - Few measures are available to assess the health status of the growing numbers of children who now survive long-term with chronic physical disorders. A Functional Status Measure, FS I, that had considerable promise for measuring individual child health status and characterizing populations was developed in 1978. This paper describes a revised version of that measures. Data were collected using a new sample of 732 children (aged 0 to 16 years) with and without chronic physical conditions in order to assess the psychometric properties of the new instrument. The FS II(R) has both a long (43-item) and a short (14-item) version. The long version has a total score derived from a one factor solution and a two factor solution consisting of General Health and Stage Specific factors for each age group. The 14-item version of FS II(R) uses a common core of items across the entire age span. Internal consistency estimates (alphas) for the factor-based and 14-item versions are all greater than 0.80. At each age, long and short versions behave similarly in a wide range of tests of discriminant, construct, and content validity--strong support that they constitute a common measure. The FS II(R) has excellent psychometric properties and provides concise measures of health status of children spanning the entire childhood age range from 0 to 16 years. It has particular strengths for the measurement of health status of children with chronic physical conditions who are not disabled. PMID- 2250493 TI - Use of a preferred provider plan by employees of the City of Seattle. AB - Little is known about the use of services in a preferred provider organization (PPO). We studied a preferred provider arrangement between Pacific Medical Center and employees of the City of Seattle. In the second 12 months of this program 8,529 subjects submitted at least one claim; of these, only 420 (4.9%) ever used the preferred provider. Those who used the PPO at least once differed significantly from those who never used it on age, sex, employee/dependent status, and utilization in the previous year. Outpatient and total charges were higher for PPO users than for nonusers before and after control for those characteristics. Those who used the PPO exclusively were similar to those who never used it. People who used both the PPO and other providers were at higher risk for use of services, and had much higher overall utilization, with or without control for other variables. No differences were found between people who obtained only a small proportion of their services at the PPO and those who had most (but not all) of their use at the PPO. Many of these findings can be explained by a self-selection model. It is important for research on PPOs to have an independent manner of assessing who is a PPO user. PMID- 2250494 TI - Status of quality assurance programs in American hospitals. PMID- 2250495 TI - A typology of medical practice organization in Canada. Data from a national survey of physicians. AB - Different modes of practice organization may result in advantages for physicians and their patients. Compared with solo practice, group practice may produce economies of scale, efficiencies in health care delivery, and improvements in the quality of care. However, in Canada assessment of the implications of differences in practice organization have been impeded by a lack of relevant data and a tendency to treat practice type as a dichotomous variable. Conventional solo/group distinctions fail to address the significance of the growing number of medical practices that are neither solo nor group, but combinations of both, and they obscure the policy implications of the growing number of physicians in institutional as opposed to private practice. This paper develops and applies a theoretically based typology of practice organization to data collected as part of a national survey of 2,398 Canadian physicians conducted in late 1986 and early 1987. The analysis identifies six practice types, describes their distribution and operating characteristics, and identifies the characteristics of physicians working in them. PMID- 2250496 TI - The functional status of patients. How can it be measured in physicians' offices? AB - Physicians wishing to maintain the functional capacity of their patients often need, but usually do not have, practical measures of function. The Dartmouth COOP, a primary care research network, developed nine pictorial Charts to efficiently measure patient function in busy office practice. Each Chart has a five-point scale, is illustrated, and can be self-administered or administered by office staff. The Charts are used to measure the patients' overall functional health just as Snellen Charts are used to measure vision. Studies to assess the Charts' reliability, validity, acceptability and clinical utility were conducted on over 2,000 patients in four diverse clinical settings. Results show that the Charts are both reliable and valid. One-hour test-retest intraclass correlations for elderly patients ranged from 0.78 to 0.98 and from 0.73 to 0.98 for low income patients. The average Pearson product-moment correlation between Charts and previously validated measures of function was 0.61 and the Charts were as capable of detecting the association between disease and functioning as were longer, standard measures. Most clinicians and patients report that the Charts are easy to use and provide a valuable tool to measure overall function in busy office practice. For the 25% of patients in which the Charts uncovered new information, changes in clinical management were initiated for 40% of them. We conclude that the COOP Charts are practical, reliable, valid, sensitive to the effects of disease and useful for quickly measuring patient function. PMID- 2250498 TI - Measuring health changes among severely ill patients. The floor phenomenon. AB - The interest in measuring health status with survey instruments has not been matched with an analysis of their performance characteristics in the field. We used the Medical Outcome Study Short Form (MOS-20) to assess health outcomes among patients who were hospitalized in one of two public hospitals. We mailed the MOS-20 and a series of transition questions, which asked about changes in health, to patients admitted in the previous year. We received 414 completed surveys from 480 patients at baseline and follow-up data on 90% of these patients six months later. Baseline MOS-20 scores for study patients were significantly lower, corresponding to worse health, than previously reported outpatient and general population cohorts. While the direction of change on serial applications of the MOS-20 paralleled the patients' perception of change reported on transition questions, many patients who reported their health had become worse also recorded the lowest possible score on the MOS-20 at baseline. These low baseline MOS-20 scores prohibited the recognition of larger declines in function during the follow-up period. This floor in the response range creates an instrument bias against documenting a decline in health among severely ill patients, the group in which it may be most important to detect such a change. PMID- 2250497 TI - Measuring hospital performance. The development and validation of risk-adjusted indexes of mortality, readmissions, and complications. AB - In this study we used information from discharge abstracts to develop three different risk-adjusted measures of hospital performance: a Risk-Adjusted Mortality Index, a Risk-Adjusted Readmissions Index, and a Risk-Adjusted Complications Index. The adjustments have face validity, and appear to account for much of the variation across hospitals in the rates of these adverse events. The indexes are stable over time, and are not biased with respect to hospital size, ownership, or teaching status. All three indexes appear to have construct validity when tested against the changes in hospital care that occurred when PPS was introduced. PMID- 2250499 TI - Patterns of care in general hospitals for patients with psychiatric diagnoses. Some findings and some cautions. AB - Patients with psychiatric diagnoses in general hospitals in New Jersey in 1985 with and without dedicated psychiatric units are compared. Unit and nonunit bed occupants are compared also in hospitals having dedicated units. Types of referral, case-mix, length of stay, co-morbidity, transfer to other settings, and social characteristics of patients vary by type of bed. Patients in scatter beds have relatively low lengths of stay, rarely are attended by a psychiatrist and have more CAT scans and EEGs for almost every diagnostic group. These data suggest the critical need for clinical studies of quality of care in varying psychiatric inpatient settings. PMID- 2250500 TI - Predictors of older adults' longitudinal dental care use. Ten-year results. AB - Our purpose was to identify factors predictive of reported dental care use by elders (65+) over a ten-year period in Massachusetts. The Massachusetts Health Care Panel Study began in 1974-75 (wave 1) as a statewide survey of 1625 noninstitutionalized elders. Wave 2 occurred in 1976, wave 3 in 1980, and wave 4 in 1985. The 540 persons who participated in all four waves are the subject of this report. The remainder either died, entered nursing home, or were lost to follow-up. This longitudinal design permits analysis of cohort, aging, and period effects. The outcome variables were self-reported dental care use within two years, or more than two years, as reported at waves 1, 3, and 4. Wave 2 was excluded because less than two years had elapsed since the previous wave. To identify factors predictive of reported use, we used a generalization of the logistic regression model that included a random effect term, which accounts for repeated measures being made on the same subjects. Covariates in the model were dentate status, education, income, cohort, sex, martial status, and time. The variable "time" served as a measure of aging/period effects. Persons were grouped into four birth cohorts. Before adjusting for other covariates, cohort was significantly associated with dental care use, but was not so in the full multivariate model. Dentate status, education, and income were significant predictors of use. The cohort effect was explained by dentate status, education, and income. Time was not significant, indicating no aging/period effects in this ten-year period, or that their net effect was zero. PMID- 2250501 TI - Medication compliance and health education among outpatients with chronic mental disorders. AB - Medication noncompliance occurs among as many as one-third to one-half of all medical and psychiatric outpatients. Noncompliance has serious consequences for individuals diagnosed with schizophrenia, often resulting in higher rates of relapse and rehospitalization, and poorer community adjustment. Health education interventions have been shown to be effective in promoting compliance among patients with chronic medical illness such as hypertension or diabetes, but there have been few randomized trials of this approach among patients with chronic psychiatric disorders. This paper presents the results of an application of health education among a group of male psychiatric outpatients. Two interventions were developed which used health education techniques to 1) engage families or significant others as active participants in the aftercare process, and 2) train patients to become effective health care consumers. A total of 418 individuals participated in a six-month trial over a four-year study. Both interventions significantly improved medication compliance among those who received them. The results show that comparatively brief interventions can significantly alter medication compliance behavior and improve the quality of life for patients with chronic psychiatric disorders. PMID- 2250502 TI - [Prevalence of nosocomial infections in Catalonia. I. Infections and risk factors. EPINCAT study group]. AB - Following an extensive protocol, an investigation on the prevalence of nosocomial infections was carried out in May 1988 in 33 hospitals from Catalonia. A total number of 7434 patients were included. Communitary infections were also tabulated. The prevalence for nosocomial infections was 12.1% and the incidence of communitary infections was about 17.1%. The nosocomial more frequent infections involved the urinary tract (29.2%), the surgical procedures (25.6%), the low respiratory airways (17.3%), and the blood (4.9%). The prevalence of surgical infections ranged between 5.6% and 8.9%. Logistic adjustment showed that notorious risk factors for nosocomial infections are: urinary catheterization, central vascular catheterization, mechanical ventilation and tracheostomy, and the duration of hospital stay. For some infections the age, sex, risk of the baseline illness, and intrinsic risk factors appear to be important determinants of the risk. The study provided a large information regarding the distribution of hospital infections among the clinic departments, the differences depending on the hospital size, the distribution of the location of the infection, and the importance of the risk factors. Attention is directed to the need for appropriate surveillance systems to reduce the incidence of nosocomial infections. PMID- 2250503 TI - [Pulmonary disease caused by opportunistic environmental mycobacteria. Review of 35 cases]. AB - The clinical characteristics, radiologic findings, and therapeutic response in 35 cases of pulmonary disease induced by opportunistic environmental mycobacteria collected during a period of 4 years are reported. These cases included 21 infections by Mycobacterium kansasii, 10 by M. xenopi, and 4 by M. avium. The cases reported constituted the 6% of all mycobacterial infections of the lung observed in our institution. The mean age of the patients was 56 years and 83% of them were male. The presence of previous pulmonary involvement was rather frequent, specially the existence of chronic limitation of the air flow (CLAF) (91%) and previous tuberculosis (29%). The clinical symptoms were almost nonspecific and they could frequently be misinterpreted as an intercurrent infection in cases of CLAF. The radiologic findings could not be distinguished from an infection by M. tuberculosis. The clinical course with pharmacologic first line therapy (93% of cases) was satisfactory in 28 patients in whom follow up controls are available. PMID- 2250505 TI - [The silent carrier of the human immunodeficiency virus]. PMID- 2250504 TI - [Medical counseling, nursing counseling, and nicotine chewing gum for smoking cessation in primary care]. AB - The 2-month results of a study designed to compare the effectiveness of three methods to encourage giving up smoking in primary health care are reported: individualized medical counseling (minimal intervention), counseling plus follow up option by the nurse, and medical counseling plus nicotine chewing gum. Overall 425 smokers between 15 and 65 years of age were included in the study. In 349 of them (82%), short term follow-up was carried out by phone interview. The proportion who declared to have given up smoking, after adjustment for the estimated validity of the phone report of smoking status, was 10, 9%, 10.8% and 11.1%, respectively, without significant differences between the three groups. In the logistic regression analysis, only the existence of concomitant disease and the anticipated difficulty in giving up smoking appeared as predictive variables of abstention. The implications of the results for the strategies to control smoking are discussed. PMID- 2250506 TI - [Current treatment of mycobacterioses]. PMID- 2250507 TI - [Cerebral toxoplasmosis in a patients with the acquired immunodeficiency syndrome. Discussion of the criteria of computerized axial tomography]. AB - Computed tomography (CT) is a sensitive noninvasive study used for the diagnosis of cerebral lesions in patients with AIDS. Toxoplasmosis is, by far, the most common opportunistic central nervous system disease (CNS) in this population; accordingly, most groups start empirical antitoxoplasma therapy if the radiological features of the lesion suggest the diagnosis. It is common, however, when CT images do not suggest toxoplasmosis, not to start empirical therapy until the investigation of the lesion with other studies has not been completed. We report a case of cerebral toxoplasmosis in a patient with AIDS which, in our opinion, illustrates that empirical antitoxoplasma therapy should be started in all CNS lesions in patients with HIV infection while etiological investigation is undertaken, independently from the appearance of the lesion in the CT. PMID- 2250508 TI - [43-year-old male, with severe marrow aplasia, fever, abdominal pain and hemoptysis]. PMID- 2250509 TI - [Asterixis in bilateral subdural hematoma]. PMID- 2250510 TI - [Rectal sucralfate in post-irradiation hemorrhagic proctitis]. PMID- 2250511 TI - [Leukocytoclastic vasculitis secondary to flu vaccination]. PMID- 2250512 TI - [Analogs of somatostatin and carcinoid tumors]. PMID- 2250513 TI - [Abuse of the term "prospective" in clinical research articles]. PMID- 2250514 TI - [Facial hypoesthesia during mastication and hypertrophy of the masseter muscles]. PMID- 2250515 TI - [Granulomatous hypophysitis probably of autoimmune etiology. A case diagnosed post mortem]. AB - We report a case of idiopathic granulomatous hypophysitis diagnosed at autopsy in a 69-year-old female who, after endocrine coma, died from gastrointestinal hemorrhage. Immunohistochemical studies disclosed a predominance of T-lymphocytes in the inflammatory pituitary infiltrates. In addition to hypophysitis, lymphocytic thyroiditis and adrenalitis lesions and atrophic gastritis were found. These findings, consistent with autoimmune disease, are similar to those reported for lymphocytic hypophysitis, and raise the possibility that both types of hypophysitis are different aspects of the same condition. PMID- 2250516 TI - [Vasculitis associated with proliferation of large granular lymphocytes]. AB - We report a patient with the syndrome of large granular lymphocytes in whom the initial clinical features were polyarthritis, hepatosplenomegaly and neutropenia. Relative lymphocytosis was also demonstrated at the expense of a subpopulation with morphology and surface markers characteristic of large granular lymphocytes (CD2+, CD8+, CD16+ and HNK-1+). After 6 months of asymptomatic course, without changes in clinical or laboratory data, the patient died from an acute abdomen with mesenteric ischemia of different likely causes as suggested by necropsy data (multivisceral diffuse infiltrate by large granular lymphocytes, systemic vasculitis and Clostridium sepsis). The association between this syndrome and systemic vasculitis is discussed. PMID- 2250517 TI - [Cancer and quality of life]. PMID- 2250518 TI - [Cerebral infarct of the lacunar type]. PMID- 2250520 TI - [Inaccuracies of "chi square"]. PMID- 2250519 TI - [Distribution width of erythrocyte size]. PMID- 2250521 TI - [Acute pancreatitis secondary to the administration of 6-mercaptopurine]. PMID- 2250522 TI - [Cyclosporin and deep venous thrombosis]. PMID- 2250523 TI - [Brain metastasis from infiltrating carcinoma of the bladder]. PMID- 2250524 TI - [Castleman's disease and amyloidosis]. PMID- 2250525 TI - [Enteritis caused by Isospora belli in patients with the acquired immunodeficiency syndrome. Description of 9 cases]. AB - The features of the nine first cases of Isospora belli enteritis in patients with acquired immunodeficiency syndrome (AIDS) diagnosed in the Hospital Clinic i Provincial of Barcelona from September 1984 to May 1989 are reported. All patients were male, five were homosexual and four were parenteral drug abusers. The clinical presentation was watery diarrhea without pathological products lasting for more than one month. Five patients had features of dehydration, five had malabsorption, two had fever and one had metabolic acidosis. Enteritis by I. belli was the first opportunistic infection in eight of the nine cases. The number of T4 lymphocytes was lower than 0.4 x 10(9)/l in four of the seven patients in whom it was measured, and the p24 antigen was detected in serum in three out of five. The response to co-trimoxazole, both in the acute phase and as maintenance therapy, was satisfactory; however, two patients had recurrences despite maintenance therapy with co-trimoxazole. In one of them I. belli was clinically resistant to co-trimoxazole therapy and to other drugs, the diarrhea only responding to the administration of a somatostatin analogue (SMS 201-995). PMID- 2250526 TI - [Thyrotropic hormone in an adult population seeking care at a primary health care center]. AB - In a study of the need for detecting subclinical hypothyroidism in a population aged 60-80 years, the measurement of thyrotropin with the immunofluorometric technique in 446 individuals seeking attention identified 58 with high TSH (greater than 4 microU/ml); only 33 of these were evaluated in a specialized endocrinological unit. The abnormality was confirmed by radioimmunometric technique in 19 patients (4%), and in the remaining 14 individuals disease was ruled out. The prevalence in this group of individuals is comparable to that found in other studies which recommend screening for subclinical hypothyroidism, but the requirement for the implementation of such a screening program in our area should be carefully evaluated before it could be recommended. PMID- 2250527 TI - [Importance of risk factors in the extension of pulmonary thromboembolism]. AB - The cases of pulmonary thromboembolism (PTE) diagnosed in the clinical autopsies performed in our hospital during a 15-year period were reviewed. The incidence was 2.7% (63 cases). The most common disease associated with thromboembolism was cancer (41%). In 30 cases, thromboembolism involved more than 60% of the pulmonary circulation (group I), between 40% and 60% in 18 cases (group II), and less than 40% in 15 cases (group III). 30% of the embolisms were recurrent. A statistically significant correlation between the extension of the involved pulmonary circulation and the condition associated with thromboembolism was found. Whereas in patients with neoplasia the extension of pulmonary circulation involved by PTE was quite variable, the patients with cardiovascular disease or thrombophlebitis had PTE with invariably severe compromise of pulmonary vasculature (groups I and II). PMID- 2250528 TI - [Angioimmunoblastic lymphadenopathy]. PMID- 2250529 TI - [Cancer of the pancreas: an ecologic study]. AB - The geographical pattern of mortality due to cancer of pancreas was evaluated in Spain for both sexes, calculating the standardized mortality ratios (SMR) for each province during the period 1975-1980. A multiple linear regression study with a group of environmental variables was carried out. The expenditure on food during the periods 1964-65, 1973-74 and 1980-81 (based on the family budget surveys from the National Institute of Statistics) its volume among these variables. As the most relevant finding, a positive association between death from pancreatic cancer and cheese consumption was observed for the three studied periods: 1964-65 (p less than 0.01 for both sexes), 1973-74 (p less than 0.01 in males) and 1980-81 (p less than 0.02 in males). The validity of these results is analyzed, and an assessment of these studies for the etiological investigation of disease, called ecological studies, is also made. PMID- 2250530 TI - [Hypothyroid myopathy. A clinical and histologic prospective study of 19 patients]. AB - Nineteen patients with primary hypothyroidism were prospectively studied before starting replacement therapy with thyroid hormones. Most patients had mild to moderate muscle symptoms: generalized muscle weakness, myalgia and cramps, and increased serum levels of muscle enzymes. In two patients these features were the motive for consulting the physician. The patients with muscular features had significantly higher plasma levels of lactic dehydrogenase and aldolase than asymptomatic patients. The major histological muscle findings were atrophy of type II fibers, abnormalities in the oxydative pattern of muscle cells, and glycogen deposition. In the biochemical investigations an increased muscle glycogen with reduced activity of the glycolysis and glucogenolysis enzymes were found. The patients with more marked histological abnormalities had lower levels of thyroid hormones, but the differences did not reach significant values. Five patients in euthyroid status after 12 months of therapy underwent a new biopsy. Although the remaining clinical and laboratory parameters had returned to normal, some of the histological muscle abnormalities persisted. This finding leads to the suspicion that the lack of thyroid hormones may induce irreversible structural damage in skeletal muscle. PMID- 2250531 TI - [Secondary amyloidosis and rapidly progressing renal insufficiency. A clinico pathologic study]. AB - In the present study, 7 patients with secondary amyloidosis and renal involvement who developed rapidly progressive deterioration of renal function are reported. After the investigation of the possibly implicated clinicopathological factors a cause was found for 3 patients. In the remaining 4 patients, the rapid evolution to end stage renal disease was attributable to the rapid progression of amyloid deposits by itself. A correlation between the evolution of renal function, vascular amyloid deposits and interstitial fibrosis is reported. PMID- 2250532 TI - [Microangiopathic thrombotic syndromes in adults: results of treatment with intensive plasmapheresis]. AB - The response to intensive plasmapheresis was evaluated in 13 patients (7 males, 6 females; median age 28 years) with microangiopathic thrombotic syndromes (MTS) who were treated at our center during the last 10 years. The most common initial clinical features were anemia, hemorrhage and neurologic abnormalities. Twelve patients had severe thrombocytopenia and 8 had renal failure. Fourteen plasmapheresis courses were carried out to treat 13 initial episodes and one relapse. The mean volumes of removed plasma and fresh frozen plasma infused at each exchange were 57 ml/kg and 41.7 ml/kg, respectively. Eight patients received antiplatelet drugs and/or corticosteroids. After a mean number of 10.6 exchanges per patient and course, complete remission (CR) was achieved in 7 cases (6 initial episodes and one relapse) and a partial response in 3. Four patients did not respond to therapy and died from progression of the disease. The early institution of plasmapheresis and the rapidity to respond were the only factors significantly associated with the achievement of CR. PMID- 2250533 TI - [Prognosis in cancer of the colon]. PMID- 2250534 TI - [Benefits of better control of arterial hypertension]. PMID- 2250536 TI - [Inhibition of angiotensin converting enzyme: a decade's experience]. PMID- 2250535 TI - [Pleural effusion associated with primary lymphedema: a rare combination. Apropos of a case]. AB - A case of exclusive association of pleural effusions and primary lymphedema, without ungual dystrophy is described. This isolated combination is an uncommon clinical condition with only 11 cases reported in the literature. The pathogenesis is characterized by aplasia-hypoplasia of the lymphatic vessels with consequent defective lymphatic drainage. We present a pleural effusion associated with a left lower extremity cellulitis, we argue about the differential diagnosis and treat the patient with thoracocentesis and aspiration with a favourable evolution without recidive. PMID- 2250537 TI - [Diving accidents (1). Decompression sickness]. PMID- 2250538 TI - [A specification]. PMID- 2250539 TI - [Flumazenil in the treatment of hepatic encephalopathy]. PMID- 2250541 TI - [Active euthanasia and medical ethics]. PMID- 2250540 TI - [Is renal vascular amyloidosis clinically relevant?]. PMID- 2250542 TI - [Immunohistochemical profile of epithelioid sarcoma: study of a case localized to the hand]. PMID- 2250543 TI - [Epidemiologic surveillance of hospital infection. Preliminary analysis of a 5 year series]. AB - The epidemiological surveillance provides opportunities to know the magnitude and determinants of nosocomial infection and permits, at the same time, the planning, implementation and evaluation of prevention and treatment activities in order to approach the rates of infection in the hospital, as near as possible, to the irreducible minimum. We show data collected by surveillance system Guadalajara General Hospital from 1982 to 1987. In order to analyze general trends, seasonality, accidental variations and endemic levels, we have used statistical methods as linear regression, chi 2, equality proportions and built of an endemic channel with confidence intervals of 95%. We have observed a decreasing trend, locating endemic levels around to 4% of monthly accumulated incidence. There is a possible seasonal influence concurring with holidays periods and someone accidental variation over that we expected, it was related with a deteriorated situation about medical care. PMID- 2250544 TI - [Serum 1,25-dihydroxyvitamin D in insulin-dependent diabetes mellitus]. AB - To evaluate the relationship between insulin and hormonal vitamin D system we compared the serum concentrations of 1.25 dihydroxyvitamin D (1.25 D) in a group of 56 patients with insulin dependent diabetes mellitus (IDDM) with those from a control population of 26 healthy individuals. We did not find overall significant differences in 1.25 D levels between diabetic patients and control individuals (32.6 +/- 12 vs 35.4 +/- 9 pg/ml), but there were differences between the different patient subgroups depending on the duration of the disease. The dose of insulin and the 1.25 D levels were linearly correlated (r = 0.3693, p = 0.0051). The patients with IDDM had normal 1.25 D levels. Exogenous insulin administration may have relevance for the interpretation of these results. PMID- 2250545 TI - [Pain and its treatment]. PMID- 2250546 TI - [Experimentation and animal rights: history and ethical principles]. PMID- 2250547 TI - [Familial microepidemics of tuberculosis]. AB - We report a microepidemic of tuberculosis (TBC) in a family of 12 members, 4 of which were parenteral drug abusers and 3 had anti-human immunodeficiency virus (HIV) antibodies. Four new cases were simultaneously diagnosed in the investigation of the contacts of a patient with extrapulmonary tuberculosis and acquired immunodeficiency syndrome. We review the requirements for the development of these epidemic outbreaks, both in noninfected communities and in the family contacts, where positive anti-HIV antibodies may increase the risk. We emphasize the importance of a systematic study of contacts in these families and the indication of chemoprophylaxis in all those sharing the same household, without age limit. PMID- 2250549 TI - [Eaton-Lambert myasthenic syndrome and myasthenia gravis]. PMID- 2250548 TI - [The language of pain: differential diagnosis of craniofacial pain]. PMID- 2250550 TI - [Acute focal bacterial nephritis. Apropos of a case]. PMID- 2250551 TI - [Leukocytoclastic vasculitis and famotidine]. PMID- 2250552 TI - [Antibiotic therapy in severe infections caused by Pseudomonas aeruginosa]. PMID- 2250553 TI - [Basal cell carcinoma in a patient with the acquired immunodeficiency syndrome]. PMID- 2250554 TI - [Acute respiratory insufficiency in pneumonia caused by Pneumocystis carinii with normal thoracic radiography]. PMID- 2250555 TI - [Importance of the use of drugs in the heterosexual transmission of the human immunodeficiency virus in our area]. PMID- 2250556 TI - Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis. AB - The spinal antinociceptive interaction between the opiate receptor subtype agonists morphine (mu), U69593 (kappa) and [D-Pen2,5]-enkephalin (DPDPE; delta) with clonidine (alpha 2 adrenergic) was examined. Male SD rats received fixed ratios of clonidine to morphine (10:1), U69593 (1:3), or DPDPE (10:1) through catheters terminating at the lumbar cord. Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED50 calculated. The DRCs of morphine and U69593 but not of DPDPE were parallel to the DRC of the opiate plus clonidine. Synergy was determined by isobolographic analysis. The ED50 values for the mixtures were significantly less than the theoretical additive ED50 values, indicating synergy between clonidine and morphine, U69593, or DPDPE. PMID- 2250557 TI - The Pennsylvania State University College of Medicine 1990 Bernard B. Brodie Lecture. Pharmacogenetics: past and future. PMID- 2250558 TI - Effects of irradiation and semistarvation on rat thyrotropin beta subunit messenger ribonucleic acid, pituitary thyrotropin content, and thyroid hormone levels. AB - The effect of radiation-induced anorexia on serum thyrotropin (TSH), pituitary TSH-beta mRNA, pituitary TSH content, serum thyroxine (T4), and serum 3,5,3' triiodothyronine (T3) was investigated using feed-matched controls. Rats received 10 Gy gamma whole-body irradiation and were examined 1-3 days postirradiation. Feed-matched and untreated controls were also studied. The average food intake of the irradiated and feed-matched groups was approximately 18% of the untreated controls. Over the three day period both the irradiated and feed-matched groups lost a significant amount of body weight. The serum T4 levels of both the irradiated and feed-matched groups were not significantly different from each other, but were significantly depressed when compared to the untreated control group. The serum TSH and T3 were, however, significantly greater in the irradiated than the feed-matched groups at day 3 posttreatment. To determine if the difference in the serum TSH level between the two groups was due to a pretranslational alteration in TSH production, we measured the TSH-beta mRNA using an RNA blot hybridization assay. We found that the TSH-beta mRNA level was the same in the irradiated and feed-matched groups, suggesting that the mechanism responsible for the radiation-induced increase in the serum TSH level is posttranscriptional. Pituitary TSH content in the irradiated rats was significantly less than in pair-fed controls, suggesting that irradiation may permit enhanced secretion of stored hormone. PMID- 2250559 TI - Protein kinase C translocation in human blood platelets. AB - Protein kinase C (PKC) activity and translocation in response to the phorbol ester, phorbol 12-myristate, 13-acetate (PMA), serotonin (5-HT) and thrombin was assessed in human platelets. Stimulation with PMA and 5-HT for 10 minutes or thrombin for 1 minute elicited platelet PKC translocation from cytosol to membrane. The catecholamines, norepinephrine or epinephrine at 10 microM concentrations did not induce redistribution of platelet PKC. Serotonin (0.5-100 microM) and the specific 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) (10-100 microM) but not the 5-HT1A or 5-HT1B agonists, (+/-) 8 hydroxy-dipropylamino-tetralin (8-OH-DPAT) or 5-methoxy-3-3-(1,2,3,6-tetrahydro-4 pyridin) 1H-indole succinate (RU 24969) induced dose-dependent PKC translocations. Serotonin-evoked PKC translocation was blocked by selective 5-HT2 receptor antagonists, ketanserin and spiroperidol. These results suggest that, in human platelets, PMA, thrombin and 5-HT can elicit PKC translocation from cytosol to membrane. Serotonin-induced PKC translocation in platelets is mediated via 5 HT2 receptors. PMID- 2250560 TI - Atypical endogenous opioid systems in mice in relation to an auto-addiction opioid model of anorexia nervosa. AB - We have proposed that the atypical opioid system in the mouse may be representative of that in the anorexia nervosa patient and may account for a biological predisposition to the disorder. This is in the context of our auto addiction model of anorexia nervosa in which endogenous opioids play a critical role in its etiology. Morphine activation of the endogenous opioid systems increases food intake and causes sedation in most species, including normal humans and rats. In contrast in BALB/C mice, morphine causes anorexia and hyperactivity, which we suggest may be true in the anorexia nervosa patient. A variety of atypical opioid systems have been demonstrated in different mouse strains, based on other responses. The present study examines these strains with reference to the responses relevant to our anorexia nervosa model. Three patterns are described--anorexia with hyperactivity (BALB/C and C57BL/6J mice), anorexia without hyperactivity (DBA/J mice), and a biphasic curve with hyperphagia at low doses and anorexia and hyperactivity at higher doses (CF-1 mice). Only female mice were used. These atypical opioid systems may reflect a spectrum of biological predispositions to the disorder. These strain differences may also provide useful correlations of the genetic determinants of various opiate responses and provide useful comparisons in characterizing the essential features responsible for the atypical responses. PMID- 2250562 TI - Pressor responsiveness to endothelin is not attenuated in gravid rats. AB - The aim of this study was to evaluate the effect of synthetic human/porcine endothelin (ET-1) on mean arterial blood pressure (MAP) in pregnant and non pregnant rats and to compare this to the effects of two well characterized agonists, angiotensin II (AII), and vasopressin (VP). On day 14 of gestation (parturition day 22) polyethylene catheters were chronically implanted in the abdominal aorta for monitoring of MAP and in the vena cava for administration of drugs. Pressor responsiveness was measured in conscious freely moving animals on day 20 and again on the 7th day post-partum. All three agonists increased MAP in a dose related manner. However, whereas the sensitivity of pregnant rats (P) to AII and VP was significantly blunted compared to postpartal (PP) measurements, the MAP responses to ET-1 were the same in both groups. Moreover, the combined administration of ET-1 at a subpressor dose (0.05 pmol/100 g bw) and AII or VP at effective doses significantly potentiated (particularly in P) the pressor effects of AII and VP. These results demonstrate that ET-1 and possibly other vasoactive substances of endothelial origin, override the compensatory mechanism of normal pregnancy with respect to the blunted responsiveness to AII and VP. Such a mechanism may be of particular relevance in the evolution of pregnancy-induced hypertension. PMID- 2250561 TI - Argiotoxin-636 blocks effects of N-methyl-D-aspartate on lateral line of Xenopus laevis at concentrations which do not alter spontaneous or evoked neural activity. AB - Activity of primary afferent neurons in acousticolateralis organs can be modulated by excitatory amino acids (EAA) and their antagonists, and EAA are among the better candidates for the transmitter(s) between hair cells and afferent neurons. Argiotoxin-636 (ATX) is a spider venom toxin that is a selective antagonist of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors in vertebrates. In the present study, the effects of NMDA alone and in combination with ATX on resting firing rate (spontaneous activity) and mechanically stimulated activity of lateral line afferent neurons of post metamorphic Xenopus laevis were compared. Perfusion of NMDA (100 or 200 microM) typically produced a biphasic effect on spontaneous activity consisting of a transient increase followed by a decrease in firing rate. Mechanical stimulation applied after the initial response to NMDA produced an increase in firing activity that was not significantly different from the increase in firing activity evoked in the absence of NMDA. ATX at 1-2 microM did not alter either spontaneous or evoked activity, but blocked in a reversible manner both the excitatory and inhibitory actions of NMDA on spontaneous activity. These results suggest the presence of an NMDA receptor in the lateral line but do not support the hypothesis that the generation of action potentials by the afferent transmitter is solely dependent on activation of postsynaptic NMDA receptor-ion channels. PMID- 2250564 TI - Effect of spermine on association of protein kinase C with phospholipid vesicles. AB - The in vitro mechanism by which polyamines affect protein kinase C (PK C) activation process was investigated in a reconstituted system consisting of purified enzyme and phospholipid vesicles of various phosphatidylserine content. It was found that the addition of spermine greatly interferes with the association of PK C to liposomes. This tetramine, at micromolar concentrations, was most potently effective while other polyamines such as spermidine and putrescine were almost ineffective; therefore the modulatory action appeared to be structure specific. The spermine effect is dramatically influenced by the density of the phosphatidylserine present on the liposome, suggesting the complex formation with the acidic component on phospholipid vesicles to be the mechanism by which this polyamine exerts its modulatory action. PMID- 2250563 TI - Salmon calcitonin given by nasal spray or by injection does not increase beta endorphin levels in normal men. AB - It has been suggested that the analgesic action of calcitonin (CT) might involve a stimulation of beta-endorphin (beta-EP) release. To verify whether salmon CT modifies the circulating levels of beta-EP, and whether the route of administration plays any role in this response, we have studied 10 healthy male volunteers, aged 30-40 yr. Each of them was studied on 4 different days, after administration of placebo or salmon CT (100 UI) by the intravenous, intramuscular and nasal route, in random order. Ionized calcium tended to decrease, especially after intravenous CT, but there was no change in plasma beta-EP levels, regardless of the route of administration. It is therefore unlikely that circulating beta-EP mediates any biological effect of CT. PMID- 2250566 TI - Behavioral economics of drug self-administration. I. Functional equivalence of response requirement and drug dose. AB - Response requirement and dose of drug per administration are two separate factors that have been demonstrated to control drug self-administration. Recent developments in behavioral economics have shown that these two factors are in fact functionally equivalent for nondrug reinforcers, as indicated by a unit price analysis. In this review, the unit-price notion was tested for drugs as reinforcers via a re-analysis of ten drug self-administration studies. The results of the re-analysis indicated that response requirement and reinforcer magnitude, the constituents of unit price, have functionally equivalent effects on drug consumption and that a positively decelerating demand curve is produced as unit price increases. This suggests that the behavioral-economic notion of unit price is a more parsimonious explanation of the effects of response requirement and dose in drug self-administration studies, in that it integrates and describes what was previously considered to be two distinct operations. PMID- 2250565 TI - Evidence that the reversible MAO-A inhibitor moclobemide increases prolactin secretion by a serotonergic mechanism in healthy male volunteers. AB - The serotonin receptor antagonist methysergide was used to investigate the mechanism mediating stimulation of prolactin release after single doses of the reversible MAO-A inhibitor moclobemide. Eight healthy male volunteers participated in a placebo-controlled cross-over study, where pretreatment with methysergide almost totally prevented the moclobemide-induced increase in plasma prolactin levels. MAO-A inhibition, as evidenced by up to 80% decreases in the plasma concentration of 3,4-dihydroxyphenylglycol, a deaminated metabolite of norepinephrine, was similar after both pretreatments. This result suggests that moclobemide stimulates prolactin release through activation of serotonergic receptors, and provides evidence that the drug is capable of augmenting central serotonergic neurotransmission in humans. PMID- 2250567 TI - S-emopamil ameliorates ischemic brain damage in rats: histological and behavioural approaches. AB - Transient ischemia induced by 4 vessel occlusion (4VO) in rats is known to produce neuronal damage to particular brain structures such as the CA1 sector of the hippocampus. Behavioural changes associated with ischemic lesioning of this brain region are an impairment in spatial learning of rats tested in a water maze (14). In the present study, it was investigated whether pretreatment with S emopamil, a Ca2(+)-channel blocker as well as a 5-HT2 antagonist, prevents the occurrence of hippocampal cell damage and/or spatial learning impairments in rats subjected to 4VO. Neuronal lesioning in the hippocampus was significantly reduced following pretreatment with S-emopamil in 4VO rats. In addition, S-emopamil treated animals showed an improved spatial learning ability compared to saline treated 4VO rats. It is suggested that S-emopamil may exert a protective effect under ischemic conditions. The possible mechanisms involved are discussed. PMID- 2250569 TI - Paradoxical digestion of myo-inositol phosphates by alkaline phosphatase at low pH. AB - The ability of bovine intestinal alkaline phosphatase (0.1-10 units/ml) to cleave myo-inositol bound phosphate moieties was examined. Paradoxically the digestion was optimal for a number of isomers at pH 5-7. It is possible that digestion at higher pH (9-10) does not proceed at maximal rates due to a conformation of the myo-inositol phosphate molecule which stabilizes the molecule against enzymatic attack. Alkaline phosphatase activity did not require the addition of added divalent cations. Moreover, several divalent cations, particularly zinc, were found to have a marked inhibitory effect. Further studies into this phenomenon suggested that some divalent cations can form insoluble complexes with myo inositol phosphates, particularly those possessing a number of phosphate moieties, preventing the action of degradative enzymes. On the basis of these experiments we conclude that phosphate moieties can be removed from myo-inositol using relatively low concentrations of alkaline phosphatase as long as optimal incubation conditions are selected. This includes the use of a slightly acidic incubation media without the addition of divalent cations, particularly zinc. PMID- 2250568 TI - Diazepam sensitive mice: differential sensitivity to the depressant and anticonvulsant effects of diazepam. AB - A mouse line was developed by selecting for increased sensitivity to the hypnotic effect of diazepam. These "diazepam sensitive" mice showed a mean duration of loss of righting reflex (LORR) of approximately 150 min at a dose of 20 mg/kg diazepam, this dose failed to induce LORR in the control outbred mice. Rotarod treading times of the diazepam sensitive mice were significantly shorter than that of the control mice over the same dose range indicating that these mice are also more sensitive to the sedative/muscle relaxant effects of diazepam. On the contrary, the ability of diazepam to protect against pentylenetetrazole-induced convulsion was found to be the same in the sensitive and control mice. These observations strongly suggest that the heightened sensitivity to the sedative hypnotic effects of diazepam in the sensitive mice is unlikely to be due entirely to changes in drug disposition. PMID- 2250570 TI - Cyclosporine A inhibits prostaglandin E2 release, and has no effect on renin secretion, from rat renal cortical slices. AB - These experiments were designed to test the hypothesis that cyclosporine A (CSA) inhibits renin secretion and stimulates renal prostaglandin E2 (PGE2) release in vitro. In rat renal cortical slices incubated at 37 degrees C in a buffered and oxygenated physiological saline solution containing 4 mM KCl, CSA concentrations ranging from 1 to 30 microM had no significant effect on renin secretion. Furthermore, partial depolarization of the cells, produced by increasing extracellular KCl concentration to 20 mM, failed to reveal any latent inhibitory or stimulatory effects of CSA on renin secretion. On the other hand, PGE2 release was significantly inhibited by CSA over the same range of concentrations. This inhibitory effect might be explained by the previous findings of others, that CSA inhibits phospholipase A2 activity, thereby decreasing arachidonic acid production, the rate-limiting step in PG synthesis. In conclusion, CSA inhibits PGE2 release but fails to affect renin secretion in vitro. These results suggest that the occasional effects of CSA on renin secretion in intact animals must be attributable to indirect and/or chronic effects. PMID- 2250571 TI - Existence of carcinine, a histamine-related compound, in mammalian tissues. AB - Carcinine (beta-alanylhistamine) was synthesized in vitro from histamine and beta alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissue of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and in the mammalian physiologic response to stress. PMID- 2250572 TI - Protective effect of Sn-protoporphyrin against doxorubicin-induced perturbations of heme metabolism. AB - The administration of doxorubicin, an anti-tumor antibiotic, to rodents resulted in an increase in heme oxygenase activity and a decrease in delta-aminolevulinate (ALA) synthase activity and in cellular heme and cytochrome P450 content in liver. Sn-protoporphyrin, a potent inhibitor of heme degradation both in vitro and in vivo, when administered to rodents prior to doxorubicin, mitigates the drug-induced toxic actions which are reflected by the drug-induced decreases of both cellular heme and cytochrome P450 content. Sn-protoporphyrin thus provides a pharmacological means of protecting against the toxic effects of doxorubicin and other drugs which enhance heme oxygenase activity and thus decrease cellular heme and cytochrome P450 content in vivo. PMID- 2250573 TI - Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. AB - Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the contralateral side showed relief of the MPTP induced parkinsonian symptoms. The subsequent bilateral injection of the excitatory amino acid antagonist allowed the monkey to move freely, unhindered by tremor or rigidity. In addition unilateral injections of the NMDA antagonist MK 801 (5, 25 and 50 ug) within the medial pallidum also produced dose-related rotational behaviour, with alleviation of parkinsonian symptoms in the contralateral limbs. Systemic administration of MK-801 (1 ng/kg - 1 ug/kg i.m.) was without effect. PMID- 2250574 TI - The effect of serotonergic agents on haloperidol-induced catalepsy. AB - The effect of various classes of serotonergic agents on haloperidol-induced catalepsy was evaluated in male Sprague-Dawley rats. The 5-HT-1A agonists buspirone, ipsapirone and 8-OH-DPAT all potently reversed catalepsy. The mixed 5 HT-1A and 5-HT-1B agonist RU 24969 reversed catalepsy only at the highest dose tested. The non-selective 5-HT-1 antagonist (l)-propranolol did not affect catalepsy. The 5-HT-2 agonist DOI and 5-HT-2 antagonist mesulergine both reversed catalepsy. ICS 205-930 (5-HT-3 antagonist) reversed catalepsy at low doses only. Another 5-HT-3 antagonist, GR 38032F, had no effect on catalepsy. These studies suggest that 5-HT-1A and 5-HT-2 receptor sites are important in the serotonergic modulation of haloperidol-induced catalepsy. PMID- 2250575 TI - Cocaine attenuates the severity of naloxone-precipitated opioid withdrawal. AB - Cocaine dependence in opioid addicts is associated with less severe naloxone precipitated opioid withdrawal compared to opioid addicts who are not cocaine dependent, suggesting that cocaine may reduce opioid withdrawal severity. The present study examines this effect further by comparing withdrawal severity in these two groups of opioid addicts. To control for dose, length of exposure, and time of administration of drugs, we also studied this effect in rats. Cocaine reduced the overall severity of opioid withdrawal in both human and rat. This drug-drug interaction may occur through alpha-2 adrenergic neurons in the locus coeruleus, similar to the effect of clonidine on opioid withdrawal. PMID- 2250576 TI - Computer-assisted analysis of dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1 propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine. AB - Computer-assisted analysis of self- and cross-displacement studies between dextromethorphan (DM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine ((+)-3 PPP) demonstrated in the rat brain the existence of two high-affinity and one low affinity binding site for each ligand. One high-affinity site is the common DM1/sigma 1 site, the affinity of which is allosterically increased 4 to 5-fold by 10 microM ropizine. The Kd values of the DM1/sigma 1 for DM and (+)-3-PPP are 17 and 11 nM respectively. DM binds to the second high-affinity site (R2) with a Kd of 15 nM; this site has low affinity for (+)-3-PPP. Conversely, (+)-3-PPP binds with high affinity (Kd 53 nM) to another site (R3), that has low-affinity for DM. The Bmax of the common DM1/sigma 1 site in the rat is about ten times smaller than that in the guinea pig. Thus, extreme caution should be exercised in extrapolating from one species to another. Since DM and most sigma ligands bind to more than one site, not all of which are shared, it is important not to attribute the complex pharmacological effects of these ligands to a single hypothetical receptor. PMID- 2250577 TI - Prolactin-releasing effect of tryptolines in the developing and adult male and female rats. AB - The developmental prolactin-releasing effect of Tryptoline (T), Methoxytryptoline (MT) and Hydroxytryptoline (OHT) was examined comparatively in male and female rats. A single injection of T 15 mg/Kg increased serum prolactin in both sexes; the increase was significant from day 20 onwards. OHT evoked a sharp rise in 12 day-old rats and the releasing effect increased with age, both in males and females. No significant sex differences were observed in T or OHT treated rats. MT caused an increment in prolactin secretion in male rats and this action increased with age. The releasing effect of MT was not significant in females, even at 38 postnatal days. In adult animals, the tryptolines (15 mg/Kg) were able to increase serum prolactin in males and in females in diestrous; a dose of 5 mg/Kg of T was only effective in adult male rats. The prolactin-releasing effect was drastically reduced by orchidectomy and by ovariectomy. LH, FSH and TSH were not modified by any treatment. The present results show for the first time the ontogeny of the prolactin-releasing effect of tryptolines in male and female rats and that this effect depends on the presence of gonadal secretions in adults. PMID- 2250578 TI - Chronopharmacological study of furosemide; (VI). Influence of prolonged exposure to continuous light. AB - We have previously reported that a time-dependent variability is observed in the diuretic effects of furosemide in rats. The present study was undertaken to examine the influence of prolonged exposure to continuous light on chronopharmacological profiles of furosemide in Wistar rats. In study I, rats were maintained for more than 2 weeks under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs) (L-D). Furosemide (30 mg/kg) was orally given at 1200 hrs or at 2400 hrs. Urine was collected for 8 hours after the drug and urinary excretion of sodium and furosemide were determined respectively. Thereafter, these rats were exposed to continuous light (L-L) for the next 4 weeks, and were again maintained under the L-D cycle. The identical trial of study I was repeated at the end of the L-L (study II) and the second L-D (study III) conditions. Urine volume and urinary excretion of sodium and furosemide following the drug were significantly greater at 1200 hrs than at 2400 hrs under conditions of L-D (study I and III). However these administration time-dependent changes in the effects of furosemide and its urinary amount disappeared with L-L condition (study II). These findings indicate that the mode of the time-dependent changes in the effects of furosemide is altered by prolonged exposure to continuous light. PMID- 2250579 TI - Prazosin unmasks a renin response to intravenous para-chloroamphetamine. AB - When injected intraperitoneally, p-chloroamphetamine (PCA) causes the acute release of catecholamines and serotonin, increases mean arterial pressure (MAP) and increases plasma renin activity (PRA) in rats. Experiments were designed to determine the dose-response and time-course for the effect of PCA administered intravenously on PRA in conscious, unrestrained rats. It was found initially that intravenous doses of PCA ranging from 0.3 - 6.0 mg/kg caused rapid and marked hypertension, but produced variable effects on PRA for up to 30 minutes after injection. In a second study PCA (0.3 - 6.0 mg/kg) did not alter PRA at 30 or 60 minutes after intravenous injection, but did increase PRA 60 minutes after 10 mg/kg, intraperitoneally. When the hypertension elicited by intravenous PCA was abolished by pretreatment with the alpha 1-adrenoceptor antagonist prazosin (100 micrograms/kg, iv), PCA produced marked elevations in PRA from 15 - 60 minutes. Thus it appeared that the renin response to intravenous PCA was masked by an elevation in MAP; when the vascular response to PCA was blocked, a large increase in PRA was observed. PMID- 2250580 TI - Bacitracin U.S.P. contains a factor that stimulates receptors for 5 hydroxytryptamine on rabbit aortic strips. AB - Bacitracin (BAC) U.S.P., obtained in the form of sterile powder, elicits dose dependent and non-tachyphylactic contractions of the rabbit isolated aorta and of other rabbit vessels. The use of several pharmacologic antagonists suggests that BAC is a 5-hydroxytryptamine mimetic in aortic strips, since the antibiotic is competitively antagonized by methysergide and ketanserin with pA2 values compatible with an agonist action on the 5-HT2 receptors found in the aortic preparation. It remains to be determined whether bacitracin A, the chief constituent of BAC U.S.P., is the 5-HT agonist. PMID- 2250581 TI - Effects of muscimol and flurazepam on the sleep EEG in the rat. AB - In order to assess the possible role of GABA receptor function in the hypnotic property of benzodiazepines, we have examined the sleep EEG in rats given the GABA agonist muscimol, alone and in combination with flurazepam. Muscimol 0.05 and 0.1 mg/kg IP failed to alter sleep latency or total sleep time, and did not interact with the sleep-enhancing properties of flurazepam 20 mg/kg IP. These observations, in conjunction with a previous study of bicuculline, suggest that the hypnotic property of benzodiazepines may not be mediated by alteration of GABAergic activity. PMID- 2250582 TI - Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties. AB - Several new chemical entities (RP 52891, cromakalim and its derivatives) are potent and specific openers of vascular K+ channels. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemma K+ channels produces loss of cytosolic K+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. The former effect is not modified by specific blockers of classical vascular receptors but it is completely antagonized by the hypoglycemic sulphonylurea, glibenclamide, an established blocker of ATP regulated K+ channels. K+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium. This salutary effect is mediated via cardiac K+ channel modulation and may result from an improved myocardial oxygen balance in the ischemic region. K+ channel openers increase plasma renin activity in animals as well as in man. However, only diazoxide, but not cromakalim or RP 52891, lowers plasma insulin concentration. The dose of glibenclamide entirely blocking the latter effect is over 50-fold smaller than that antagonizing the hypotensive and hyper-reninemic responses to diazoxide. In conclusion, K+ channel activators are potent vasorelaxant and cardioprotective agents possessing an original mechanism of action which is the opening of plasmalemma ATP-regulated K+ channels. Their clinical use as antihypertensive agents may be accompanied by undesirable effects (characteristic of peripheral vasodilators) which are likely to be attenuated or avoided by controlled release formulations. However, inasmuch as low doses of K+ channel openers may be sufficient to produce selective coronary artery dilatation and cardioprotection, these compounds could be of particular value in treating patients with coronary artery disease efficaciously and possibly without adverse cardiovascular effects. PMID- 2250583 TI - A mutant protein of human interleukin-1 beta with immunostimulatory but not pyrogenic potency. AB - Interleukin-1 (IL-1) mediates a variety of immune and inflammatory responses. In order to understand the mechanisms involved in multiple biological functions, it is important to define the active sites of IL-1. Using the technique for site specific mutagenesis, we tested whether the arginine residue at the 4th position in human IL-1 beta is essential for multiple biological activities. In our experiments, the fourth position is replaced by a non-basic amino acid--either glycine or aspartic acid. The resulting mutant protein shows both immunostimulatory activity and the ability to induce hematopoietic growth factors similar to native IL-1 beta, but has a markedly reduced pyrogenic potency. Therefore, the mutant protein of IL-1 beta may represent a good candidate for use in vivo as an adjuvant for poor immunogenic vaccines. PMID- 2250584 TI - Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior. AB - Behavioral sensitization can be observed with repeated administration of amphetamine where the intensity of motor stimulation increases over time. The process of sensitization has been well characterized, however, the neurochemical mechanisms that are critical for the development of sensitization are not known. In the present study, the role of the hypothalamic pituitary adrenal axis (HPA) in the development of behavioral sensitization to amphetamine was explored by pretreating rats with an intravenous administration of an antiserum to corticotropin-releasing factor in a volume that has been shown to block significantly stress- and cocaine-induced activation of the HPA. Four groups of eight rats were pretreated intravenously with either heparinized saline or CRF antiserum and subcutaneously with saline or d-amphetamine in a balanced design. The rats were then returned to their home cages and left undisturbed for seven days after which they were given three consecutive behavioral tests with saline SC, 0.75 mg/kg d-amphetamine SC, and 3.0 mg/kg d-amphetamine SC. The rats pretreated with intravenous CRF antiserum showed a significant attenuation of the development of d-amphetamine-induced sensitization but the antiserum did not alter the magnitude of the behavioral response to the initial, sensitizing dose of d-amphetamine. These results suggest that activation of the hypothalamic pituitary adrenal axis may be of critical importance to the development of behavioral sensitization to amphetamine. PMID- 2250585 TI - Binding and solubility of oleic acid to laboratory materials: a possible artifact. AB - The possibility that significant amounts of fatty acids were dissolved in or bound to the surfaces of common laboratory materials was examined. The uptake or adsorption of radioisotopically labeled oleic acid and cholic acid by plastic tubing of Tygon, Teflon, and polyethylene, and Pyrex, and borosilicate glass, and steel was measured. 3H-oleic acid and 14C-cholic acid were used in the presence of different concentrations of unlabeled oleic acid, cholic acid, and/or bovine serum albumin. Concentrations, composition, pH, and perfusion rates were varied. Relatively large amounts (10-95%) of oleic acid (25 microM) were lost by dissolving in plastic and adsorption to glass or metal. The degree of losses decreased in the presence of compounds in the perfusion solution which could bind or dissolve oleic acid. In contrast, cholic acid was not lost to plastic, glass or metal. The magnitude of and influence of perfusion rate, composition, pH, and sequence of perfusion solutions on oleic acid losses were sufficiently large that the results of certain studies, such as those of unstirred water layers of albumin - stimulated fatty acid uptake by hepatocytes may need to be reexamined. PMID- 2250586 TI - Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues. AB - A method combining data on fatty acid composition into subsets is used to illustrate general relative competitive selectivities in the metabolic and transport events that maintain fatty acid compositions in tissue lipids and to minimize differences among tissues or species in the amount of individual fatty acids. Fatty acid compositions of triglycerides and phospholipids in several tissues of the rat were maintained with simple relationships between the exogenous n-3 and n-6 dietary polyunsaturated fatty acids and the endogenous n-7 and n-9 types of fatty acid. The general pattern of fatty acids in triglycerides was similar for liver, plasma and adipose tissue, averaging about 30% as saturated acids, 67% as 16- and 18-carbon unsaturated acids and only about 2% as 20- and 22-carbon highly unsaturated acids. The tissues maintained a linear relationship between the amount of 18-carbon polyunsaturated fatty acids in the diet and in the tissue triglycerides, with the proportionality constant for 18:3n 3 being 60% of that for 18:2n-6. The total phospholipids of liver, plasma and red blood cells maintained about 45% of the fatty acids in the form of saturated fatty acids and 20-30% as 20- and 22-carbon highly unsaturated fatty acids irrespective of very different proportions of n-3, n-6 and n-9 types of fatty acids. In all three tissues, the 20-carbon highly unsaturated fatty acids of the n-3, n-6 and n-9 type were maintained in a competitive hyperbolic relationship with apparent EC50 values for dietary 18:2n-6 and 18:3n-3 near 0.1% of dietary calories. The consistent quantitative relationships described in this study illustrate an underlying principle of competition among fatty acids for a limited number of esterification sites. This approach may be useful in predicting the influence of diet upon tissue levels of the substrates and antagonists of eicosanoid biosynthesis. PMID- 2250587 TI - Tissue phospholipid fatty acid composition in genetically lean (Fa/-) or obese (fa/fa) Zucker female rats on the same diet. AB - The fatty acid composition of serum total lipids, of phospholipids of various organs (liver, heart, kidney), and of nervous structures (brain, retina, sciatic nerve, myelin, synaptosomes) have been compared in lean (Fa/-) and genetically obese (fa/fa) Zucker female rats. Both received a standard commercial diet including 37% of 18:2n-6 and 5% of n-3 polyunsaturated fatty acids (PUFA), 1.7% of which were in the form of 20:5n-3 and 22:6n-3. In comparison with lean rats, the results for the obese rats pointed out (i) no difference in the fatty acid composition of nervous structures; (ii) a decrease of 18:2n-6 (from -8% to -35%) and of 20:4n-6 (from -9% to -49%) in serum, liver and in kidney; this was compensated for by an increase in 20:3n-6 (from +30% to +320%) and in total n-3 PUFA (from +68% to +76%); (iii) a decrease of 20:4n-6 (-18%) and of 22:6n-3 ( 24%) in heart compensated for by an increase in 18:2n-6 (+39%) and in 20:3n-6 (+233%); and (iv) constant levels of total PUFA (n-6 and n-3) in the various fractions studied, except in serum where this level decreased (-23%). Finally, except for the nervous structures, tissue phospholipids of obese rats included a lower proportion of 20:4n-6 and a higher proportion of 20:3n-6. This resulted in a significant reduction in the 20:4n-6/20:3n-6 ratio; by contrast, the 20:3n 6/18:2n-6 ratio increased. The results suggest that in Zucker rats, the obese character (fa/fa) affects the desaturation-elongation process of 18:2n-6 to 20:4n 6 by specifically decreasing delta 5-desaturase activity. PMID- 2250588 TI - Fatty acid content of marine oil capsules. AB - The use of dietary omega 3 fatty acid capsules has been associated with a decrease in plasma triglyceride levels. In addition, populations consuming diets rich in fish appear to have a decreased incidence of cardiovascular disease. Eicosapentaenoic acid (EPA, 20:5 omega 3) and docosahexaenoic acid (DHA, 22:6 omega 3) are major fatty acids in fish oils. It is believed that fish oils exert their biologic effect through these fatty acids. Many individuals are currently taking fish oil capsules to lower lipids, increase bleeding time, and possibly decrease cardiovascular risk. These capsules also have been classified as food additives with less stringent controls on content. We assessed the fatty acid, cholesterol, and vitamin A and E content of eight commercially available capsules along with cod liver oil. The content of EPA was found to range from 8.7-26.4% (wt %) with a mean of 17.3% (82.4% of labeled content), and that of DHA from 8.9 17.4% with a mean of 11.5% (90.0% of labeled content) as assessed by capillary column gas-liquid chromatography. The mean content of the polyunsaturated omega 3 fatty acids was 31.9%, and that of the omega 6 fatty acids was 1.4%. The content of saturated fatty acids was 32.0%, and that of monounsaturated fatty acids was 25.1%. Cholesterol content was low, with a range of 0.7-8.3 mg/g, the alpha tocopherol range was 0.62-2.24 mg/g, and the range of retinyl esters was 0.4 298.4 micrograms/g. Cod liver oil had substantially more retinyl esters (2450.1 micrograms/g) than did fish oil capsules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250589 TI - Exchange of free cholesterol between plasma and erythrocytes from hyperthyroid and hypothyroid rats in vitro. AB - In our previous studies, we found that circulating thyroid hormone levels alter cholesterol partition between plasma and erythrocytes by changing the phospholipid content of erythrocytes (Ruggiero, F. M., et al. (1984) Horm. Metabol. Res. 16, 37-40; Ruggiero, F. M., et al. (1987) Lipids 22, 148-151). As an extension of this work, we now followed the exchange of free cholesterol between plasma and erythrocytes in control, hyperthyroid and hypothyroid rats under various experimental conditions in vitro. In control rats, erythrocytes incubated with plasma at 37 degrees C for 4 hr lose 10% of cholesterol which was esterified by lecithin:cholesterol acyltransferase (LCAT) present in the plasma. In hyperthyroid rats, erythrocytes incubated with plasma lose 30% of cholesterol within the same time. By contrast, in the case of hypothyroid rats incubation for 4 hr was necessary to transfer 24% of free cholesterol from plasma to erythrocytes. Inhibition of cholesterol esterification did not affect the loss of erythrocyte cholesterol in control and in hyperthyroid rats. Ca2+ increased the LCAT activity in the plasma of these rats. The findings shed light on the role of thyroid hormones in regulating cholesterol levels in plasma through active cholesterol transfer between plasma and erythrocytes. PMID- 2250590 TI - The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes. AB - The suppression of plasma very low density lipoprotein (VLDL) triglyceride levels by dietary fish oils rich in polyunsaturated n-3 fatty acids has been attributed to decreased hepatic VLDL secretion. To investigate the effect of n-3 fatty acids on lipid metabolism and VLDL secretion in a tissue culture system, we incubated rabbit hepatocytes with oleic acid and eicosapentaenoic acid (EPA) and examined [3H]glycerol and [14C]fatty acid incorporation into hepatocyte triglyceride and phospholipid and into media VLDL. Glycerol incorporation studies showed that EPA failed to stimulate VLDL triglyceride secretion from hepatocytes as occurred with oleic acid (P less than 0.05). Oleic acid preferentially enhanced hepatocyte triglyceride synthesis while EPA stimulated significantly phospholipid synthesis (P less than 0.01). Varying the relative concentrations of oleic acid and EPA at a constant total fatty acid concentration corroborated preferential triglyceride synthesis from oleic acid. Synthesis shifted predominantly to phospholipids with increasing concentrations of EPA and lower levels of oleic acid. Incorporation of the [14C]fatty acids (800 microM) followed similar patterns: 87% of [14C]oleic acid was incorporated into hepatocyte triglyceride and 44% of [14C]EPA was assimilated in hepatocyte phospholipid (p less than 0.001). Fatty acids at trace concentrations (53 nM) showed a more divergent pattern of lipid incorporation: 60% of [14C]oleic acid was incorporated into triglyceride while 91% of [14C]EPA was incorporated into phospholipid (p less than 0.001). We conclude that in primary rabbit hepatocyte culture, which appears to be a useful model to study lipid metabolism and VLDL secretion, EPA is avidly incorporated into phospholipid while oleic acid predominantly becomes esterified in triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250591 TI - Reduction in microalbuminuria in diabetics by eicosapentaenoic acid ethyl ester. AB - Eicosapentaenoic acid (EPA) ethyl ester (1.8 g/d) was administered to 16 diabetic patients (5 insulin-dependent and 11 noninsulin-dependent diabetics) for 6 mon. EPA in total plasma fatty acids increased from 4.0 +/- 2.4 mol% (mean +/- SD) to 7.5 +/- 3.1 mol% (p less than 0.001). Albumin excretion, measured with spot urine, was significantly reduced from 65 to 36 mg/g creatinine (geometric means, p less than 0.001). Fasting blood sugar levels, glycohemogloblin, body weight and blood pressure did not change significantly during the study. There were also no significant changes in serum levels of creatinine, urea nitrogen, total cholesterol and triglycerides. Although no overt hemorrhage was observed in the patients, hematocrit was reduced from 42.6 +/- 2.8% to 41.0 +/- 3.9% (p less than 0.02). Ten other similar diabetic patients (4 insulin-dependent and 6 noninsulin dependent diabetics) were followed as a reference group, not concomitantly, for 6 mon with neither EPA ethyl ester nor placebo. The parameters mentioned above were not changed significantly in this group during 6 mon. EPA administration might retard the appearance of overt diabetic nephropathy. PMID- 2250592 TI - On the effect of peroxisomal beta-oxidation and carnitine palmitoyltransferase activity by eicosapentaenoic acid in liver and heart from rats. AB - Repeated administration of highly purified eicosapentaenoic acid (as ethyl ester) resulted in a decrease in plasma triglycerides and high density lipoprotein (HDL) cholesterol. This was accompanied by a stimulation in the activities of carnitine palmitoyltransferase, fatty acyl-CoA oxidase and peroxisomal beta-oxidation in the liver. The results suggest that the triglyceride-lowering effect observed with eicosapentaenoic acid may be due to a reduced supply of fatty acids for hepatic triglyceride synthesis because of increased fatty acid oxidation. Eicosapentaenoic acid feeding marginally affected the triglyceride content of heart and mitochondrial and peroxisomal enzyme activities. PMID- 2250593 TI - Intestinal absorption of retinol and retinyl palmitate in the rat. Effects of tetrahydrolipstatin. AB - The aim of the present study was to characterize the intestinal absorption of retinol and retinyl palmitate in thoracic duct and bile duct fistulated rats and to investigate the effect of a simultaneously administered lipase inhibitor, tetrahydrolipstatin (THL). Absorption was determined as lymphatic recovery over a 24-hr period, including an initial 12-hr continuous intraduodenal infusion of either [11,12-3H]retinol or [11,12-3H]retinyl palmitate given in emulsified glyceryl trioleate or in mixed micellar solution of monoolein and oleic acid. From micellar dispersion, labeled retinol and retinyl palmitate were recovered in the lymph to 50-60% and both to the same extent. Administered in emulsified form, labeled retinol from fed retinyl palmitate was recovered to 47%, but retinol from fed retinol to only 18%. THL (10(-4) M) in the infusate had no significant effect on the recovery of 14C-labeled oleic acid. The recovery of label from emulsified glyceryl tri[1-14C]oleate was significantly decreased at this concentration of THL (76.5% vs 19.6% recovery). When administered in emulsified form, retinol absorption was not significantly affected by THL at 10(-4) M, while retinyl palmitate absorption was very significantly decreased (5.0% compared to 47.8%). In the presence of THL, retinol absorption from retinyl palmitate in micellar solution was decreased (from 58% to 17%). Most of the retinol in the lymph extracts (72.2 to 91.3) was present as retinyl ester, regardless of the chemical and physical form of administration. Furthermore, THL did not induce any change in this pattern. PMID- 2250594 TI - Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets. AB - The fatty acid composition of phospholipids in peritoneal exudate cells and spleen cells was assessed in five rat strains fed four test diets of differing fatty acid composition. Distinctive patterns of fatty acids were seen in the total phospholipid preparations in both cell types in response to the diets which contained either olive, sunflower, linseed or fish oil. In general, similar fatty acid profiles were seen in each of the rat strains fed the same diet with the only evidence of possible genetic (strain) variation being a relative deficiency of delta 4 desaturase in Dark Agouti rats. PMID- 2250596 TI - Arteriolar network morphology in gracilis muscle of rats with salt-induced hypertension. AB - The purpose of this study was to determine if structural rarefaction of arterioles occurs in the gracilis muscle of Dahl salt-sensitive (DS) rats with salt-induced hypertension. Arteriolar network architecture was studied in cleared muscles removed from DS fed either a high (7% NaCl) or low-normal (0.45% NaCl) salt diet for 4 weeks. Muscles removed from Dahl salt-resistant (DR) rats on high and low-normal salt diets served as controls. The 7% NaCl diet had no effect on arterial pressure in DR, but caused marked hypertension in DS. The density of arcade arterioles was significantly lower in DS than in DR (0.77 vs 1.26 segments/mg tissue, respectively) and was unrelated to either dietary salt content or mean arterial pressure in both strains. The number of transverse arterioles/mm parent vessel was 19% lower in DS on 7% NaCl than in DS on 0.45% NaCl and DR on either diet. These data indicate that compared to normotensive DR, the DS rat with salt-induced hypertension exhibits a lower vascular density within both the arcading and the transverse portions of the gracilis muscle arteriolar network. The lower arcade vessel density reflects an inherent characteristic of the DS strain, whereas the lower transverse arteriole density reflects a true structural rarefaction associated with salt-induced hypertension. PMID- 2250595 TI - Liver phosphatidylcholine hydroperoxidation provoked by ethionine-containing choline-deficient diet in mice. AB - It is shown that peroxidation of phosphatidylcholine (PC) is enhanced in liver of mice fed a hepatocarcinogenic choline-deficient diet containing 0.1% w/w ethionine. Mice were divided into 4 groups and fed for 4 weeks one of the following diets: choline-supplemented; choline-supplemented containing ethionine; choline-deficient; and choline-deficient containing ethionine. Phosphatidylcholine hydroperoxide (PCOOH) of liver lipids was measured by high performance liquid chromatography using a chemiluminescence detector. Mice fed a choline-deficient diet containing ethionine showed 6-fold higher PCOOH levels than the choline-supplemented control mice: the PCOOH/PC molar ratios of liver lipids were 32.3 X 10(-5) and 5.6 X 10(-5), respectively. In addition to this remarkable degree of lipid peroxidation in liver of mice fed the choline deficient diet containing ethionine, we also observed a significant liver fatty infiltration, a decrease in plasma and liver alpha-tocopherol, and an increase in liver injury-indicative enzyme activities. Also, marker enzymes for hepatocarcinogenesis, glucose-6-phosphatase and gamma-glutamyl transpeptidase were affected. These data suggest that enhanced hydroperoxidation of phosphatidylcholine may participate in hepatocarcinogenesis provoked by choline deficiency in the presence of ethionine. PMID- 2250597 TI - Plasma skimming in serial microvascular bifurcations. AB - Red cell distribution in simple two bifurcation networks has been studied experimentally. The results indicate that fractional red cell flux/fractional volumetric flow curves can be asymmetric at the downstream bifurcation. The important parameters affecting this asymmetry are the fractional flow into the upstream branch Q1*, and the ratio of the distance between junctions to the volumetric flow rate, z/Q. The asymmetry is attenuated as z/Q increases. In 50 micron tubes with Q1* of 0.5, symmetric phase separation behavior is regained when z/Q is greater than 200 sec/mm2. In 25-micron tubes symmetry is recovered before z/Q reaches the value of 50 sec/mm2. These results agree with in vivo data of previous studies and provide additional evidence that flow history can be important in microvascular networks if junctions are close together or flow rates are sufficiently high. PMID- 2250598 TI - Endothelin-induced vasoconstriction of small resistance vessels in the microcirculation of the rat cremaster muscle. AB - Recently, a peptide (endothelin) which has been shown to have potent vasoconstrictor properties has been isolated from the vascular endothelium. In the present study, we assessed the responsiveness of small arterioles and venules in the rat cremaster muscle to topical application of endothelin using closed circuit television microscopy. Exposure to increasing concentrations of endothelin (10(-15)-10(-7) M) produced a dose-dependent constriction in large (90 +/- 8 microns), intermediate (50 +/- 6 microns), and small (21 +/- 4) arterioles. Large (144 +/- 17 microns) and intermediate (79 +/- 18 microns) venules also constricted to the peptide, but the responses were inconsistent and smaller in magnitude. The constriction to endothelin was long lasting and resistant to washout. Arteriolar reactivity to endothelin was similar for all vessel levels with ED50 values ranging from 10(-9) to 10-s;1(0) M. Exposure to the calcium entry blocker, verapamil, attenuated the endothelin-induced constriction in 3A arterioles, suggesting that the constriction in skeletal muscle arterioles is at least partially due to the increased entry of extracellular calcium. PMID- 2250599 TI - The paradox of increased microvascular visualization with decreased perfusion in cerebral focal ischaemia in a primate model. AB - Microvasculature of the right caudate nucleus and insular cortex of monkeys with their right middle cerebral artery occluded was morphometrically measured with an image analysis system at 1/2, 4, 12, 24, and 48 hr and 2 weeks. A biphasic change in the microvasculature was observed. In the first phase up to 12 hr an increase in the number and length of the total microvasculature, visualized by alkaline phosphatase staining, along with a reduction in the number and length of the perfused part of the microvasculature, visualized by India ink perfusion, was observed. In the second phase after 48 hr, the number and length of the total microvascular bed as well as the perfused functional bed were significantly reduced. PMID- 2250600 TI - Microvascular hemodynamics in experimental arthritis: disparity between the distribution of microspheres and plasma flow in bone. AB - The microcirculation in normal and arthritic juxtaarticular bone was studied in 16 young dogs with carragheenan-induced arthritis of one knee. The regional blood flow was determined by the tissue uptake of intracardially injected 15-microns 141Ce-labeled microspheres, and the microvascular plasma volume was determined by the distribution space of circulating 125I-fibrinogen. Disparities between the distribution of plasma flow and microspheres, introduced by plasma skimming or nonentrapment of spheres in the intraosseous circulation, were estimated by 59Fe transferrin, a third intravascular tracer, injected as a bolus intracardially and trapped peripherally after 15 sec by prompt circulatory arrest. The tissue uptake of the plasma flow tracer was compared to that of microspheres by the ratio between observed and expected activity of 59Fe-transferrin, the expected activity being calculated from the microsphere distribution. The transferrin and microsphere uptake agreed well in patella, marginal epiphyseal bone, and cortical bone, whereas observed activity of transferrin was twice the expected in central epiphyseal bone, three times higher in marrow, and up to eightfold higher in metaphyses adjacent to growth plates. This discrepancy was significantly greater in arthritic bone when the metaphyses were examined in toto. The microsphere method thus appears to underestimate blood flow to cancellous bone and marrow due to uneven distribution of plasma and formed elements from profound plasma skimming and perhaps also by AV shunting. PMID- 2250601 TI - A method for isolation and fluorescent labeling of rat neutrophils for intravital microvascular studies. AB - A method for the isolation, fluorescent labeling, and reinfusion of rat neutrophils for in vivo investigation of white blood cell function in the microcirculation is described. The cell surface morphology and function of the labeled and unlabeled neutrophils were compared in vitro and in vivo. The morphology of the labeled and unlabeled cells was visually assessed by differential interference contrast microscopy before and after exposure to the chemotactic peptide FMLP. Labeled and unlabeled cells were morphologically similar under normal and stimulated conditions. The chemotactic responsiveness of the labeled and unlabeled cells was evaluated in vitro by quantifying the movement of cells across a porous membrane in response to FMLP. No significant difference in chemotactic responsiveness was found. The in vivo behavior of the labeled neutrophils was quantitatively studied by examining their interactions with the venular endothelium in the rat cremaster muscle. Rolling velocity for labeled neutrophils and unlabeled white blood cells was measured at different flow velocities and wall shear rates. No difference was found between the labeled and unlabeled cells. It is concluded that this isolation and labeling procedure yields cells possessing normal morphology and function. These labeled neutrophils may be useful for in vivo study of their behavior in the microcirculation. PMID- 2250602 TI - Initial equilibration of albumin and IgG in rabbit hind paw skin and lymph. AB - To determine if the interstitial distribution of plasma proteins influences transport from plasma to lymph, the initial plasma-to-extravascular and plasma-to lymph equilibrations for 131I-labeled rabbit albumin and 125I-labeled rabbit IgG were compared in hind paw heel skin of anesthetized New Zealand White rabbits. Plasma specific activities were maintained constant with time using continuous infusions. The plasma space in skin samples taken at the end of the experiment was estimated by a 3-min accumulation of 59Fe-labeled bovine transferrin. Albumin and IgG concentrations in plasma, lymph, and skin were determined by rocket electroimmunoassay. The lymph specific activity relative to that of plasma for the larger sized IgG was significantly greater (P less than 0.01) than that for albumin during the initial 8 hr of equilibration. The tissue specific activity relative to that of plasma for IgG was significantly less (P less than 0.01) than that for albumin. The distribution space at lymph concentration for both proteins was 1 ml/g dry skin wt, indicating similar excluded volumes. These data are consistent with the hypothesis that convective movement of plasma proteins through the interstitium affects lymph equilibration while diffusion affects tissue equilibration. PMID- 2250603 TI - Transport of fluid and macromolecules in tumors. II. Role of heterogeneous perfusion and lymphatics. AB - We have recently developed a general theoretical framework for transvascular exchange and extravascular transport of fluid and macromolecules in tumors. The model was applied to a homogeneous, alymphatic tumor with no extravascular binding. For this simplified system, the interstitial pressure was found to be a major contributing factor to the heterogeneous distribution of macromolecules within solid tumors. A steep pressure gradient was predicted at the periphery of the tumor. Our recent experiments have verified these predicted profiles. The purpose of this investigation was to apply this theoretical framework to the more realistic case of a nonuniformly perfused tumor. The role of lymphatics for macromolecular transport was also studied using the model. The uptake and distribution of IgG and its fragment, Fab, were simulated. The novel result from this work is that necrosis does not reduce the central interstitial pressure in a tumor. Other results showed that (i) macromolecules do not penetrate a necrotic core at early times after injection; (ii) at longer time periods after a bolus injection (days for Fab, months for IgG in a tumor of radius approximately 1cm) a "reservoir" of material may be formed in the necrotic core; (iii) continuous infusion or repeated injections should maintain a higher interstitial concentration of macromolecules; and (iv) lymphatics, if present in a tumor, would rapidly remove material and result in much lower concentration levels. The model is also used to explain some previous experimental data in the literature on antibody distribution. PMID- 2250604 TI - Endothelium and pericyte interdigitation: pathway for epidermal growth factor? PMID- 2250605 TI - [Effects of cigarette smoking on blood and alveolar air levels of benzene]. AB - Benzene was measured in blood and alveolar air of a group of 168 subjects, consisting of 34 chemical industry workers exposed to benzene and 134 definitely not occupationally exposed to benzene. A gas chromatographic method was used with mass spectrometry and cryogenic trap. The results of the biological measurements were compared with the environmental levels of benzene in the room where samples were taken and at the worksite during the previous day's shift. All environmental air samples showed measurable levels of benzene, which agrees with the observations of many authors, according to which benzene is a common pollutant also of the living and external environments. Benzene in blood measured on morning samples was correlated with the previous day's exposure. In the group of non-exposed, both blood and alveolar concentrations of benzene were significantly higher in the 68 smokers than in the 66 non-smokers and the biological levels of benzene were inversely correlated with the time that had elapsed since the last cigarette smoked. In the chemical workers, the high biological levels of benzene due to occupational exposure largely exceeded the variations in concentration due to cigarette smoking and cancelled out the differences between smokers and non smokers. It can therefore be assumed that smoking was not influential and did not interfere with the interpretation of the results in the occupationally exposed workers. Lastly, cigarette smoking, as a cyclical and additional factors of exposure, seems to be responsible for the disturbance in the relationships between biological benzene levels and ubiquitous environmental pollution, a relationship that was only observable in non-smoking subjects not occupationally exposed, but not in the group of smokers. PMID- 2250606 TI - [A method for measuring urinary concentrations of benzene. Its use in monitoring of subjects exposed to low levels]. AB - Benzene is a widely diffuse solvent (atmosphere, cigarette smoke, some foods); in the industrial environment benzene is currently present at concentrations of ppm. A valid method of biological monitoring that is easy to perform is needed for assessing occupational and non-occupational exposures. A new method has been developed to evaluate low concentrations of benzene in urine samples by means of a "dynamic" headspace (50 ml of urine in a 120 ml vial). The urine is saturated with anhydrous Na2SO4 in order to support the entrance of benzene in the air over the urine. The solvent is stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap 100 tube) by means of a suction pump (150 ml/min). A simultaneous intake of filtered air through a charcoal tube allows wash-up of the headspace. Benzene is thermically desorbed and injected in a column (Thermal tube desorber-Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1 60 m length, 0.75 mm I.D., 1 micron film thickness; G.C. Dani 8580 FID). The detection limit of the method is about 50 ng/l and the variation coefficient is 4.7%. The method was checked on urine samples of 5 non-smokers and 5 smokers: mean values of 135 and 944 ng/l respectively were obtained. A further analysis on urine samples of 60 smokers revealed a significant relationship (p less than 0.001) between urinary benzene concentrations and C0 alveolar concentrations (r = 0.626). A close relationship between benzene exposure levels and urinary concentrations was found in a group of workers exposed to low environmental benzene concentrations (mean value 1200 micrograms/m3) (r = 0.763). PMID- 2250607 TI - Mental abilities of workers exposed to aluminium. AB - The authors tested the psychic abilities of workers occupationally exposed for several years to high environmental aluminium concentrations with psychomotor ability tests, Wechsler's test of intelligence and Bender's test for estimation of cerebral damage. Slower psychomotor reaction and dissociation of oculomotor coordination were found in the exposed workers. Also, exposed workers had reduced memory ability and their mental and emotional balance was disturbed. The observed changes in psychomotor and intellectual abilities could be a consequence of the long-lasting toxic effects of aluminium. PMID- 2250608 TI - [Interdigital pilonidal sinus in barbers]. AB - Three cases of barber's hair sinus of the hand are presented. The lesion is produced by the penetration of extraneous short hairs into the interdigital spaces of the hand. The hairs produce an inflammatory reaction and foreign body granuloma. The clinical picture is usually benign but can be complicated by repeated infection which may require surgery. The structure of the lesions varies from epithelial-lined tract, cyst with surrounding foreign body reaction, to fibrotic cicatricial tissue. The exact reasons for the lesion are not known, but several theories are offered. It is, however, clear that since the 1970's Italian barbers have changed their methods of cutting hair, using their hands more than the customary instruments, i.e., combs, brushes, etc. The authors discuss the occupational problems due to the complications of disabling lesions. PMID- 2250609 TI - [Asthma caused by cyanoacrylic glues]. AB - Cyanoacrylate-based glues have been reported as producing dermatitis and bronchial asthma. The paper describes the case of a patient occupationally exposed to Loctite 406, who developed irritation of the skin and mucosae of the face and late bronchial asthma. Preventive measures for subjects exposed to cyanoacrylic instant glues are discussed. PMID- 2250610 TI - [Validity of some urinary tests considered singly or in combination in the study of renal effects of cadmium]. AB - A number of indicators of renal effect (N-acetyl-glucosaminidase, retinol binding protein, beta-2-microglobulin, albuminuria) were measured in 42 cadmium-exposed workers divided into 3 subgroups on the basis of the results of the last 10 years' biological monitoring (less than 3, 3-10, greater than 10 micrograms/l). An increase in the first three indicators was observed, particularly in the third subgroup, which, however, due to the wide dispersion of the values, was not statistically significant by the Kruskal-Wallis test. Taking the indicators singly, the marked increase in RBP and beta-2-microglobulin in the heavily exposed subjects was confirmed, along with an increasing sensitivity for NAG, while albuminuria levels were unchanged. Assessment of the "degree of association" of the altered tests demonstrated that the number and type of "association" varies between the subgroups in relation to the exposure conditions: in the first group there were no associations between the altered tests, whereas there were 2 duplicates in the second and 2 duplicates, 2 triplicates and 3 quadruplicates in the heavily exposed group. In the study of the renal effects of cadmium, it is therefore advisable to use several indicators and assess their behaviour both singly and combined, and also analyse the altered tests on the basis of the number and type of "association". PMID- 2250611 TI - [Diagnosis of occupational tumors in penal jurisprudence]. PMID- 2250612 TI - [Seropositivity and the work place. A problem which requires cooperation of the labor physician and the infection specialist]. PMID- 2250613 TI - The principles of predicting the individual risk of silicosis and silicotuberculosis. AB - A series of investigations conducted in different "silicosis-risk" industries using a methodology based on the mathematical theory of pattern recognition has shown that in the given conditions of dust exposure, the probability of contracting pneumoconiosis depends for each individual on a complex influence of many factors, both environmental and intrinsic for the individual. Genetic predisposition was one of the most important factors and while the direction in which a factor influences predisposition was the same in every industry, its relative contribution to predisposition to simple silicosis was different in the studied working populations. So a reliable prediction of the high probability of this form of pneumoconiosis on the basis of such a multifactorial analysis is possible only with respect to specific conditions of a particular industry. The complex of factors determining predisposition to silicotuberculosis is more general: this complex comprises both factors influencing susceptibility to silica dust and specially those influencing susceptibility to tuberculosis. Despite the low prevalence of genetic resistance to pneumoconiosis in working populations, the risk of contracting the disease in modern industrial conditions of relatively low dust exposure is high only for a proportion of workers for whom the genotype of predisposition to silicosis or to silicotuberculosis coincides with a most unfavourable combination of non-genetic factors enhancing this predisposition. In the opinion of the authors, the task of screening off those applicants for a "silicosis-risk" employment for whom the risk may be estimated as high on the basis of the developed methodology, is quite feasible. PMID- 2250614 TI - [Effects of the body in personal sampling of noise]. AB - In acoustic free fields the human body changes the energy distribution surrounding it, mainly under narrow band or pure tone noise conditions. Hence, sound levels measured close to the body should be intrinsically incorrect if performed via personal sampling. An experiment was carried out to verify whether this statement is still valid in a diffuse field, such as occurs in industrial workplaces. Noise measurements were made in diffuse field laboratory conditions without the presence of a person (steady state) and were repeated close to the ear of a person (perturbed state). The measurements were carried out with integrating precision sound level meters and also with personal noise dose meters. The trials were repeated in an industrial environment. The states 1/3 octave band levels were matched, as also were the equivalent continuous levels. These findings show that in diffuse fields the human body does not significantly affect equivalent continuous level measurements performed near the body. The mean differences between equivalent continuous levels measured by sound level meter were less than 0.3 dBA, and ranged from -0.6 to 0 dBA between levels measured by sound level meter and by personal noise dose meter. The results of the trial performed in the plant showed closer differences between steady and perturbed states and between sound level meter and personal noise dose meter measurements. PMID- 2250615 TI - Intestinal calcium absorption. Interplay of paracellular and cellular pathways. AB - Intestinal absorption of calcium as characterized by studies in the rat follows both mediated mechanisms through enterocytes as well as fluxes between epithelial cells. Data summarized in this review suggests that the extracellular or paracellular route in distal small intestine plays a dominant role in calcium absorption at luminal calcium concentrations above 1 mM; proximal small intestine and cecum/colon show a much greater dependence on cellular translocation processes. The wide spectrum of paracellular:cellular transport ratios found in the intestine suggests a well-adapted mechanism to minimize energy expenditure for calcium absorption in the presence of adequate dietary calcium with capacity for efficient calcium scavenging when dietary supplies are limited. No evidence to date supports a role for vitamin D in the control of paracellular calcium absorption. Other mechanisms regulating paracellular calcium absorption will undoubtedly become a significant new area for future inquiry. PMID- 2250616 TI - Transcaltachia, vesicular calcium transport, and microtubule-associated calbindin D28K: emerging views of 1,25-dihydroxyvitamin D3-mediated intestinal calcium absorption. AB - Within the past 5 years it has become apparent that the biological actions of the seco-steroid 1,25-dihydroxyvitamin D3 are more complex than previously realized. Many cell types respond in both a classical genomic manner, as well as in a nongenomic fashion to 1,25(OH)2D3. In intestine, the presumptive nongenomic effects of the seco-steroid result in transcaltachia, the rapid, hormonal stimulation of calcium transport. To better understand nongenomic points of regulation in the intestine, studies were undertaken to identify the subcellular components of the 1,25(OH)2D3-stimulated calcium transport pathway. This research has revealed the existence of a vesicular transport mechanism, an involvement of microtubules, and microtubule-associated calbindin-D28K. PMID- 2250617 TI - Mechanism and regulation of intestinal phosphate absorption. AB - Proper absorption of inorganic phosphate (Pi) from the lumen of the small intestine is of great importance for the achievement of Pi homeostasis. Although due to intralumenal H+ and Pi concentrations, Pi probably can be absorbed as H2PO4- by passive means in the duodenum, transepithelial transport of HPO4(2)- requires uptake from the lumen by an active transport system. The latter has been identified in many species as a Na(+)-Pi cotransport system at the brush-border membrane of the enterocyte. Although it is still a matter of debate whether the intestinal Na+ gradient-driven Pi transport system is electrogenic or electroneutral, there is agreement that the transporter accepts H2PO4- and HPO4(2)- alike. Recently, two laboratories independently isolated a Na(+)-Pi binding protein which has been tentatively identified as part of the Na(+)-Pi cotransport system. Movement of Pi from the cytosol across the basolateral membrane into the interstitial space has only been preliminarily characterized as transfer by facilitated diffusion. Na(+)-Pi cotransport across the brush-border membrane is under control by the active vitamin D metabolite, 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3). The sterol increases the intrinsic activity, i.e. the number and/or mobility of Na(+)-Pi carriers through genomic and probably also nongenomic actions. In addition, the rate of Na(+)-gradient-driven Pi transport can be enhanced by the hormone also through reduction of transmembrane Na+ fluxes so that more energy for translocation becomes available from the transmembrane Na+ gradient. Evidence is accumulating that thyroid hormones as well as glucocorticoids, apart from stimulating vitamin D-independent Pi uptake, potentiate the effect of 1,25-(OH)2D3 on Na(+)-Pi cotransport across the brush border membrane. PMID- 2250618 TI - Examination of the mechanism of Na+/phosphate cotransport. Use of fluorophosphate and the nature of cotransporter functional asymmetry. AB - The effect of substrates and mono- and di-fluorophosphates on Na+/phosphate cotransport by intestinal SDS-BBM vesicles was examined. Internal Na+ inhibited Na+/phosphate cotransport and this inhibition was relieved by internal phosphate. Inhibition by internal Na+ displayed Michaelis-Menten kinetics in contrast to the sigmoidal behavior for Na+ activation of phosphate uptake. Difluorophosphate but not monofluorophosphate inhibited Na+/phosphate cotransport in the external medium. In contrast, in the absence of internal Na+ monofluorophosphate but not difluorophosphate inhibited phosphate uptake. These results suggest that the intestinal Na+/phosphate cotransporter is functionally asymmetric in its substrate specificity. PMID- 2250619 TI - In vivo intestinal absorption of calcium in humans. AB - We reviewed data on calcium absorption in humans, mainly focusing on concentrations of soluble calcium in the gut, kinetics of absorption, correlation of net absorption with serum 1,25-(OH)2-vitamin D, and adaptation to different intakes. We conclude: (a) most of the unabsorbed food calcium is insoluble when it reaches the terminal ileum; (b) calcium absorption in jejunum is both active and passive with active component being dependent on vitamin D; ileal absorption is also highly dependent on vitamin D, but it is uncertain whether this action is on the active or passive component; (c) the relative role of vitamin D-dependent and vitamin D-independent mechanisms to dietary calcium absorption depends upon serum 1,25-(OH)2-D level and calcium intake; (d) over short periods, the gut reduces calcium absorption much more in response to a high-calcium diet than it increases absorption in response to a low-calcium diet. We also evaluated the measurement of 'true' calcium absorption by isotopic methods. By ignoring isotopic equilibration, these methods overestimate both the amount of calcium secreted into and absorbed from the gut. Since altered gut physiology and pathology can variably affect isotopic equilibration, 'true' absorption may not reflect absorption of dietary calcium in an individual patient. Moreover, only net absorption has metabolic and nutritional significance. PMID- 2250620 TI - Intestinal calcium transport in systemic disease. Studies with brush-border membrane vesicles. AB - Recent experiments utilizing brush-border membrane vesicles (BBMV) from small intestine to examine calcium uptake processes by the enterocyte are reviewed. Results demonstrate that (a) uptake must be examined in the time frame approaching initial rate, and (b) kinetics of saturable and nonsaturable processes be defined. Saturable uptake of calcium is carrier mediated, since it is inhibited competitively by strontium and noncompetitively by magnesium. Intravesicular strontium (but not magnesium), doubles Vmax for saturable uptake of calcium from the medium (countertransport), consistent with a mobile carrier. Since membrane lipid composition is expected to be an important determinant of function of a mobile carrier in a lipid bilayer, BBMV were treated with liposomes to change phospholipid and cholesterol content. Any change from native lipid composition decreased Vmax, but in treated BBMV, Vmax correlated with BBMV cholesterol content and fluidity. Since nonsaturable calcium uptake is extensively inhibited by both strontium and magnesium, electrostatic binding of calcium to the membrane is a major component of nonsaturable uptake. The remaining uninhibitable component of nonsaturable uptake is diffusion down the calcium concentration gradient. These concepts are applied to considering calcium uptake in disease and to the relationship of uptake to transenterocyte calcium movement. PMID- 2250621 TI - Intestinal calcium transport in the spontaneously hypertensive rat. AB - Alterations in intestinal transport and absorption of calcium have been described for the spontaneously hypertensive rat (SHR) as compared to the normotensive Wistar-Kyoto rat (WKY). Several in vitro studies of intestinal calcium transport done with everted gut sacs and the Ussing chamber found that calcium transport was lower in the SHR than the WKY. Calcium uptake by isolated enterocytes was also lower in SHR than WKY. However, net intestinal calcium absorption measurements by the balance method are variable in the literature with findings of decreased, increased, and no difference in absorption reported for the SHR. Study differences in age of the animals and diets may explain some of the disparate findings. The possible relationship between systemic alterations in calcium metabolism, including intestinal transport and absorption, and the pathogenesis of hypertension is discussed. PMID- 2250622 TI - Effect of age on calcium and phosphate absorption. Role of 1,25-dihydroxyvitamin D. AB - In humans, there is a decrease in intestinal absorption of Ca with age and a decrease in the capacity to adapt to a low Ca diet. The rat has been used as an animal model in which to study the mechanisms responsible for this decreased absorption and adaptation with age. Intestinal absorption of Ca and Pi declines with age in the rat. The decline is primarily in the energy- and vitamin D dependent component of transport found in the duodenum and, in the case of Pi transport, in the proximal jejunum. Administration of 1,25-dihydroxyvitamin D (1,25(OH)2D) increases Ca and P transport in all age groups, but the maximal levels attained are less in older animals compared to the young. Feeding a low-Ca diet increases serum 1,25(OH)2D levels and intestinal Ca absorption only in young animals. However, a low-Ca diet increases intestinal Pi absorption in all age groups, even in the absence of elevated serum 1,25(OH)2D levels. Knowledge of the mechanisms responsible for the age-related decrease in Ca and Pi absorption may suggest new ways of improving mineral absorption in the elderly. PMID- 2250623 TI - Vitamin D-independent regulation of calcium and phosphate absorption. AB - Convincing evidence for the stimulatory action of 1,25-dihydroxyvitamin D (1,25(OH2)D) on transcellular absorption of calcium (Ca) and inorganic phosphate (P) has led to the consensus that this hormone is the major regulator of Ca and P absorption. Careful review of the literature, however, suggests important regulation of Ca and P absorption by factors and agents other than those mediated by vitamin D. Thus, in rapidly growing neonatal rats, the intestine is insensitive to vitamin D and Ca absorption is entirely mediated through passive mechanisms. Patterns of change in Ca absorption associated with pregnancy and lactation are identical in vitamin D-replete and vitamin D-deplete rats. The presence of active Ca and P absorption in young, growing rats rigidly deprived of vitamin D and of active Ca and P secretion in mature rats optimally replete with vitamin D, also suggests the participation of non-vitamin D factors in the regulation of intestinal Ca and P absorption. The possibility that Ca and P in the peri-enterocyte environment may regulate their own absorption is discussed. Kinetic analysis of 1,25(OH2)D-induced transport mechanisms indicates that saturation would occur at low substrate concentrations, thus raising the question whether these mechanisms would have major regulatory roles under normal dietary conditions. There is also suggestive evidence indicating that even under conditions of low dietary Ca or P intake, the adaptive changes in intestinal absorption may not be mediated by vitamin D alone. Bile salts, lactose and prolactin are discussed as examples of agents which can stimulate Ca and/or P absorption through vitamin D-independent mechanisms. PMID- 2250625 TI - Intestinal absorption of minerals: experimental and clinical. PMID- 2250624 TI - Site and mechanism of intestinal magnesium absorption. AB - Despite considerable research on magnesium (Mg) absorption there is still uncertainty regarding the site and mechanism of intestinal Mg transport. A careful review of the literature indicates that while Mg is absorbed throughout the intestine, the predominate site is the distal small intestine. There are three mechanisms by which Mg has been shown to cross the intestine:passive diffusion, solvent drag, and active transport. The importance of each of these mechanisms to total Mg absorption is discussed. Studies in both humans and experimental animals indicate that passive diffusion through the paracellular pathway accounts for the majority of Mg absorbed. Investigators have also consistently demonstrated the existence of a saturable component. Studies in everted gut sacs, however, have failed to demonstrate that Mg is actively transported against a concentration gradient in young or adolescent rats. Recent studies using the Ussing chamber have documented that Mg is actively transported in the descending colon. PMID- 2250626 TI - Intestinal calcium transport: the cellular pathway. AB - The active calcium transport process in the intestine is transcellular. Entry across the brush border of the enterocyte is down an electrochemical gradient, probably via calcium channels. The entry process, although modified by vitamin D, does not appear to be the rate-limiting step, as total vitamin D deficiency lowers the rate of entry only by about a third, whereas active calcium transport is wholly inhibited. Calcium extrusion is effected by the Ca-ATPase, is against an electrochemical gradient, and requires a supply of energy. However, it is not the rate-limiting step, as extrusion capacity is more than sufficient to handle the maximum transcellular flux of calcium. It is the flow of calcium inside the cell, from the brush-border pole to the pump at the basolateral side, that is rate-limiting. Basal calcium flow, in the absence of the cytosolic, vitamin D dependent calcium-binding protein, CaBP, is only about 1/70 of the maximum rate, Vm, in the vitamin D-replete duodenum. CaBP levels vary linearly with the Vm. Moreover, interference with calcium binding by CaBP interferes with active calcium transport. Active calcium transport is totally regulated by vitamin D or processes that modify the action or metabolism of the sterol. Since, however, active calcium transport is only one of the two routes of calcium absorption, the other being a passive, paracellular process, up- or down-regulation of active transport may have only a limited effect on total calcium absorption. PMID- 2250627 TI - [Hemicrania and food allergy in children]. AB - Ninety-two children affected by migraine were studied, of which 49 had positive skin tests to one or more foods. Forty of those who tested positive (87%) improved after following an elimination diet for 4-6 weeks and were positive for at least one challenge test for the same types of foods which resulted in positive skin tests. Thirty-one children were cured following the elimination diet and 9 improved. At two years, despite the reintroduction of the suspected food or foods 6 to 12 months after the start of the elimination diet, these results remained unchanged. PMID- 2250628 TI - [Infantile cerebral palsy and neuromotor development in very low birth weight infants]. AB - One hundred twenty-seven children born between September 1st 1980 and August 31st 1985 weighing less than or equal to 1500 g at birth and submitted to intensive neonatal care were followed-up to the age of 12-36 months of corrected age with a follow-up program to assess their neuromotor and cognitive development. The incidence of cerebral palsy (CP) in the population in question was 15.7% at 12 and 24 months and 14.6% at 36 months. A peak CP rate was observed among those born in 1982 with a steady decline in the number of CP cases among those born in the last years of this study. The group of children with a birth weight of 1001 1500 g (VLBWI) was more heavily affected by CP than those whose weight was less than or equal to 1000 g (ELBWI). Statistical analysis revealed a significant correlation between neuromotor development and the following factors relative to the perinatal period: type of birth, sex, respiratory distress requiring assisted ventilation, acidosis, ultrasound, neurological examination at the 40th week of gestational age. PMID- 2250629 TI - [Skinfold thickness in a group of Roman schoolchildren]. AB - Triceps, biceps, subscapular and supra-iliac skinfold measurements were taken on 871 children, aged 7-14, in three Roman schools. Girls have larger skinfolds than boys; the values at every site increase with age. Boys present an increase in skinfold measurements until 11 years, then a decrease, more marked at 14 years. Skinfold measurements are a method to assess the amount of fat in the body. Age reference curves, prepared from many Authors, in various parts of the world, show differences between different populations. Skinfold reference data for Italian population therefore are necessary. PMID- 2250630 TI - [Clinico-functional evaluation of flunisolide + salbutamol combination (VAL 679/A) vs salbutamol in pediatric patients]. AB - To establish the effectiveness of flunisolide + salbutamol vs salbutamol alone administered by metered aerosol in the phlogistic obstructive diseases, 18 children were evaluated. The treatments were evaluated on the basis of ventilatory function parameters and of tolerance. The results proved positive for all drugs, though the combination flunisolide + salbutamol produced a greater ventilatory and clinical effect. PMID- 2250631 TI - [Thrombocytopenia with bilateral absence of the radius (TAR syndrome). Reports of 2 clinical cases]. AB - Thrombocytopenia with bilateral absent radii (TAR syndrome) is a hereditary condition with a recessive autosomic character. It is characterised by a series of hematological, skeletal and cardiac alterations, and also by various clinical manifestations. The frequency of this syndrome is very low. During the first months of life, prognosis is related to the severity of hemorrhage, but it improves after two years. Diagnosis is at times complex owing to the similarity between this and other syndromes. Therapy, especially during the first year of life, is based on blood transfusion. The paper describes clinical findings in two subjects admitted to the Istituto di Clinica Pediatrica. The two cases presented diverse degrees of hematological and skeletal involvement and followed different clinical evolutions. PMID- 2250633 TI - [Jarcho-Levin syndrome or spondylo-costal dysostosis. Apropos of a case]. AB - The Authors report a case of spondylo-costal dysostosis observed in a child 2 years and 1 month old. They recall its clinical and radiological findings and discuss genetic problems and differential diagnosis of this rare disease. PMID- 2250632 TI - [Endodermal sinus tumor. Histological changes induced by chemotherapy]. AB - The case of a child affected at birth sacrococcygeal teratoma is reported. Twenty eight months following surgical resection, the tumor relapsed locally and liver metastases occurred. A biopsy of the sacrococcygeal mass was performed and histologic examination proved it to be an endodermal sinus (yolk sac) tumor. Chemotherapy consisting of etoposide and high-dose carboplatin was started. When a second operation was performed the mass had disappeared and the macroscopically involved areas of liver were removed. Histologic examination demonstrated that the complete necrosis of the tumor was partially replaced by a fibrous scar tissue. The child underwent adjuvant chemotherapy and now is in complete remission fourteen months after the last operation. PMID- 2250635 TI - The physiologic effects of positioning premature infants in car seats. PMID- 2250634 TI - [Monosomy 7qter: 2 new cases of chromosomal pathology with aspecific disorders of pre- and post-natal development]. AB - Many cases of 7q deletion associated with mental retardation and multiple malformations have been described, nevertheless it is quite different to recognize common features among these infants. In this paper the cases of two female infants with uncommon facial features and 7q deletion are described. We also try to recognize the phenotypic features of this chromosomal disorder. PMID- 2250636 TI - Measuring neonatal assessment. PMID- 2250637 TI - Design issues in the NICU: thermal effects of windows. PMID- 2250638 TI - A descriptive study of sibling visitation in the NICU. AB - Factors that foster sibling involvement with the newborn and the early stages of the attachment process were cited by key experts: Brazelton and Kennell viewed organization as an essential component of any successful sibling involvement program; Rait and Barnard saw recognition of siblings' needs as vital in any effort to help them process the entire experience; and Consolvo recognized attitudinal issues as playing a key role in implementing and accepting sibling involvement. The interviews with the head nurses identified some common themes within their unique programs that centered around families, the NICU atmosphere, and the promotion of sibling activities. A liberal visiting policy was recognized in all the units, promoting the concept of family-centered care and allowing parents, siblings, and grandparents the opportunity to be supportive together. The flip side of having such a liberal visitation program was the sibling's exposure to a noisy, hurried atmosphere and parents' high anxiety level and the staff's concern about the preterm infant being subjected to a noisier, brighter, more stressful environment and possible exposure to infectious disease. The promotion of sibling activities was a recurring theme in all the head nurse interviews. Examples varied from unit to unit, but the implementation of growth and development principles, along with creativity and innovation, indicated that the overall efforts of these units in promoting sibling involvement was commendable. PMID- 2250639 TI - Breastfeeding the low-birthweight infant. AB - Human milk remains an important nutritional source for the low-birthweight infant, although supplementation may be necessary. Information on breast pumping, milk collection and storage, and breastfeeding techniques will help the new mother facilitate human milk feeding for her low-birthweight infant. Providing a supportive environment for the new mother to establish lactation at a time when her infant remains hospitalized is a challenge for the neonatal nurse. PMID- 2250640 TI - Nursing care of the infant of a diabetic mother: an antenatal, intrapartal, and neonatal challenge. AB - An understanding of the metabolic alterations seen in normal and diabetic pregnancies can lead to an optimal plan of care for the diabetic patient and her infant. The problems facing the infant of a diabetic mother antenatally, intrapartally, and neonatally relate directly to the sequence of maternal hyperglycemia, fetal hyperglycemia, and subsequent fetal hyperinsulinemia. Antenatally, intervention is aimed at identifying and preventing macrosomia and sudden fetal demise. Intrapartally, screening and monitoring are used to identify cephalopelvic disproportion and shoulder dystocia to prevent birth trauma and fetal asphyxia. During the neonatal period, a thorough assessment should be made to identify respiratory distress, birth trauma, problems with metabolic transition, and congenital anomalies. PMID- 2250641 TI - Ethics in theory and practice. Applying the decision-making model: case study 2. PMID- 2250642 TI - A new decade for NANN research. PMID- 2250643 TI - Aminoglycoside antibiotics. PMID- 2250644 TI - Asphyxiated infants: pathophysiologic consequences, parenting, and nursing management. PMID- 2250645 TI - Enhancer sequences from Arabidopsis thaliana obtained by library transformation of Nicotiana tabacum. AB - In this paper we report on the use of a bidirectional enhancer cloning vehicle to isolate and characterize new enhancer sequences from Arabidopsis thaliana. A library of A. thaliana genomic Sau3A segments was constructed in Escherichia coli in the binary plasmid enhancer cloning vehicle pROA97. The T-DNA based vector carries abbreviated TATA regions from the cauliflower mosaic virus 35S transcription unit upstream of two genes. The library was transferred via triparental mating into Agrobacterium tumefaciens. The neomycin phosphotransferase II gene was used for selection of kanamycin-resistant transformed tobacco callus cells. Approximately 1100 transgenic plants were regenerated and assayed for expression of the E. coli beta-glucuronidase (GUS) gene in leaves, stems, roots, or seeds. Plasmids carrying putative enhancer sequences were rescued from the genomes of transgenic plants and the cloned sequences were assayed for enhancer function in genetic selection experiments. Plants were regenerated from the kanamycin-resistant calli obtained in the secondary transformation experiments. Histochemical analysis of GUS activity in the leaf, stem, and root tissues of transgenic plants showed a variety of expression patterns. The DNA sequences are presented of five Arabidopsis segments which confer enhancer function. PMID- 2250646 TI - Mitochondrial genome transmission in Chlamydomonas diploids obtained by sexual crosses and artificial fusions: role of the mating type and of a 1 kb intron. AB - The linear mitochondrial DNAs of the two infertile algal species Chlamydomonas smithii and C. reinhardtii are co-linear with the exception of a 1 kb intron (alpha intron) located in the cytochrome b gene of C. smithii. C. smithii also possesses an additional HpaI restriction site (H marker) located in the COXI gene, about 5 kb from the intron. In reciprocal crosses, C. smithii (H+ alpha +) x C. reinhardtii (H- alpha -), the alpha intron is transmitted to all diploid progeny, whereas the H marker is frequently transmitted either biparentally or paternally depending on whether the C. smithii parent is maternal (mt+) or paternal (mt-). In diploids resulting from artificial fusion between vegetative cells, the absolute transmission of alpha is accompanied by the frequent transmission of the H+ marker, irrespective of the mating type of the parental strains. Finally, in reciprocal crosses between C. smithii (H+ alpha +) and recombinant H- alpha + clones, the transmission of the H marker is predominantly paternal or biparental. These results allow us to conclude that (1) the alpha intron behaves as a group I intron whose unidirectional conversion influences the transmission of the H marker; and (2) the mt- paternal mitochondrial genome is transmitted more often than the mt+. The mating type has no effect in diploids obtained by artificial fusion. PMID- 2250647 TI - Isolation and molecular characterisation of the benzoate-para-hydroxylase gene (bphA) of Aspergillus niger: a member of a new gene family of the cytochrome P450 superfamily. AB - The gene coding for benzoate-para-hydroxylase (bphA) of Aspergillus niger was cloned using differential hybridisation techniques and complementation of mutants deficient in this enzyme activity. The nucleotide sequence of the gene was determined, the presence of two introns was shown and the transcription start and termination sites were determined. The structure of the mRNA upstream from the long open reading frame (ORF) is unusual. It contains two small, overlapping ORFs whose function is unknown. Comparison of the deduced amino acid sequence of the protein with the sequences present in the databanks, indicated a significant similarity of BPH to the superfamily of cytochrome P450 enzymes. Further analysis revealed that this protein is a member of a new P450 gene family designated P450LIII. The gene is designated CYP53. To increase the BPH activity of A. niger, multiple copies of the bphA gene were introduced into the genome of a recipient strain by transformation. Although increased intracellular levels of the BPH protein could be detected, the BPH enzyme activity was decreased, suggesting titration of another essential component. PMID- 2250648 TI - Mitochondrial DNA of Chlamydomonas reinhardtii: the gene for apocytochrome b and the complete functional map of the 15.8 kb DNA. AB - We have sequenced the termini of the mitochondrial genome of Chlamydomonas reinhardtii and now present the DNA sequence of the gene for apocytochrome b. This gene is the thirteenth gene of the linear 15.8 kb DNA and appears to be the last one of the mt genome. The deduced protein sequence of 381 amino acid residues shows 56%, 48.6% and 48% identity with the apocytochrome b proteins of maize, Drosophila yakuba and mouse, respectively. RNA analysis reveals a transcript of about 1250 nucleotides. It is now possible to present the complete protein-coding capacity, the pattern of codon utilization for all eight protein genes, and the complete functional map of the mitochondrial 15.8 kb DNA of C. reinhardtii. One surprising feature is the absence of mitochondrial genes for ATPase and subunits II and III of cytochrome oxidase. No more than three tRNA genes appear to be present on the 15.8 kb mitochondrial DNA. PMID- 2250649 TI - Nucleotide sequence of the Ruminococcus albus SY3 endoglucanase genes celA and celB. AB - The complete nucleotide sequences of Ruminococcus albus genes celA and celB coding for endoglucanase A (EGA) and endoglucanase B (EGB), respectively, have been determined. The celA structural gene consists of an open reading frame of 1095 bp. Confirmation of the nucleotide sequence was obtained by comparing the predicted amino acid sequence with that derived by N-terminal analysis of purified EGA. The celB structural gene consists of an open reading frame of 1227 bp; 7 bp upstream of the translational start codon of celB is a typical gram positive Shine-Dalgarno sequence. The deduced N-terminal region of EGB conforms to the general pattern for the signal peptides of secreted prokaryotic proteins. The complete celB gene, cloned into pUC vectors, caused lethality in Escherichia coli. In contrast, celA cloned in pUC18, under the control of lacZp, directed high-level synthesis of EGA in E. coli JM83. EGA in cell-free extract, purified to near homogeneity by ion-exchange chromatography, had a Mr of 44.5 kDa. Gene deletion and subcloning studies with celA revealed that EGA hydrolysed both CMC and xylan, and did not contain discrete functional domains. EGA and EGB showed considerable homology with each other, in addition to exhibiting similarity with Eg1 (R. albus), EGE (Clostridium thermocellum) and End (Butyrivibrio fibrisolvens). PMID- 2250650 TI - Molecular cloning of the Salmonella typhimurium lep gene in Escherichia coli. AB - A system is described which enabled the selection of a heterologous lep gene, encoding signal peptidase I, in Escherichia coli. It is based on complementation of an E. coli mutant, in which the synthesis of signal peptidase I can be regulated. With this system the lep gene of Salmonella typhimurium was cloned and the nucleotide sequence was determined. The S. typhimurium lep gene encodes a protein of 324 amino acids. Expression of the gene in the E. coli mutant resulted in suppression of growth inhibition and in the restoration of processing activity under conditions where synthesis of E. coli signal peptidase I was repressed. The cloned S. typhimurium signal peptidase I had an apparent molecular weight of 36,000 daltons, which is in agreement with the calculated molecular weight of 35,782 daltons. The system described for selection of the S. typhimurium lep gene may permit the cloning and expression of other heterologous signal peptidase I genes. PMID- 2250651 TI - Transformation and recombination in rad mutants of Saccharomyces cerevisiae. AB - Disruption/deletion mutations in genes of the RAD52 epistasis group of Saccharomyces cerevisiae were examined for their effects on recombination between single- and double-stranded circular DNA substrates and chromosomal genes in a transformation assay. In rad50 mutants there was a small reduction in recombination with single-stranded DNA at the leu2-3, 112 allele; in addition there was an almost complete elimination of recombination at trp1-1 for both single- and double-stranded DNA. Reintroduction of a wild-type RAD50 gene on a replicating plasmid carrying CEN4 restored recombinational competence at trp1-1, indicating that rad50 is defective in gene replacement of this allele. In rad52 mutants a reduction of 30%-50% in recombination involving either single- or double-stranded circular DNA was observed in each experiment when compared to the wild type. This reduction of recombination in rad52 mutants was similar for recombination at the ura3-52 mutant locus where only integration events have been observed, and at the trp1-1 mutant locus, where recombination occurs predominantly by gene replacement. Neither the rad54 nor the rad57 mutations had a significant effect on recombination with single- or double-stranded DNA substrates. PMID- 2250653 TI - The extensin gene family in oilseed rape (Brassica napus L.): characterisation of sequences of representative members of the family. AB - A family of cross-hybridising cDNA clones has been isolated from a cDNA library produced with poly(A)+ RNA from the roots of oilseed-rape (Brassica napus L.). The clones were selected as abundantly expressed in root by differential screening of the root cDNA library with cDNA probes prepared from root, green leaf, etiolated leaf and developing seed. mRNA species corresponding to the selected abundant clones were expressed in roots at levels of at least 400 times those in other organs, as shown by Northern blot analysis and RNase protection assays. Complete nucleotide sequence determination of the cDNA clones showed that they encoded proteins homologous to carrot extensin and were the products of at least three different genes. An extensin gene, designated extA, was obtained from an oilseed rape (B. napus L.) genomic library screened with a cDNA species encoding a protein expressed abundantly in roots. The gene is a member of a multigene family, consisting of about 3 members per haploid genome with strong homology to the probe, and a further 20 or so members with weaker homology. The isolated gene, although not identical to the cDNA probe, was also found to be specifically expressed in roots, and was transcribed into a mRNA species approximately 1,300 nucleotides in size. A single transcription start was identified by S1 mapping. The complete nucleotide sequence of the extA gene and its flanking regions has been determined and shown to encode a protein homologous to carrot and tomato extensins. PMID- 2250652 TI - Sequence analysis of the Clostridium stercorarium celZ gene encoding a thermoactive cellulase (Avicelase I): identification of catalytic and cellulose binding domains. AB - The nucleotide sequence of the celZ gene coding for a thermostable endo-beta-1,4 glucanase (Avicelase I) of Clostridium stercorarium was determined. The structural gene consists of an open reading frame of 2958 bp which encodes a preprotein of 986 amino acids with an Mr of 109,000. The signal peptide cleavage site was identified by comparison with the N-terminal amino acid sequence of Avicelase I purified from C. stercorarium culture supernatants. The recombinant protein expressed in Escherichia coli is proteolytically cleaved into catalytic and cellulose-binding fragments of about 50 kDa each. Sequence comparison revealed that the N-terminal half of Avicelase I is closely related to avocado (Persea americana) cellulase. Homology is also observed with Clostridium thermocellum endoglucanase D and Pseudomonas fluorescens cellulase. The cellulose binding region was located in the C-terminal half of Avicelase I. It consists of a reiterated domain of 88 amino acids flanked by a repeated sequence about 140 amino acids in length. The C-terminal flanking sequence is highly homologous to the non-catalytic domain of Bacillus subtilis endoglucanase and Caldocellum saccharolyticum endoglucanase B. It is proposed that the enhanced cellulolytic activity of Avicelase I is due to the presence of multiple cellulose-binding sites. PMID- 2250654 TI - Successive binding of raf repressor to adjacent raf operator sites in vitro. AB - The raf repressor negatively regulates the transcription of the raf operon which encodes functions required for the uptake and hydrolysis of raffinose in Escherichia coli. Overexpression of the repressor gene under lac promoter control led to the formation of inclusion bodies. These were partially purified by centrifugation, solubilized in 0.1% SDS and reactivated by dilution. DNase I protection and gel retardation experiments demonstrated the specific binding of raf repressor to DNA fragments that contained the previously identified raf operator, an element comprising two 18 bp palindromic nucleotide sequences that flank the -35 raf promoter box. By using DNA fragments with one, two, or four copies of the 18 bp palindrome, these experiments revealed concentration dependent, successive occupation of all available binding sites by raf repressor. Melibiose released the repressor from the operator complexes, whereas raffinose and other alpha-galactosides did not, indicating that melibiose is the actual inducer in vivo. We suggest that successive occupation by repressor of two strategically located operator sites is a specific type of stepwise down regulation of gene expression in response to repressor concentration. PMID- 2250656 TI - Ammonia regulation of nod genes in Bradyrhizobium japonicum. AB - The expression of the nodD and nodYABC operons of Bradyrhizobium japonicum is repressed by the addition of ammonia. Repression of nodYABC expression is probably due to the effect on nodD since NodD positively regulates itself, as well as other nod operons. The effect of ammonia is independent of the known nitrogen regulatory protein, NtrC, and another regulatory protein for nitrogen fixation, NifA. PMID- 2250655 TI - Sequencing and expression of a cellodextrinase (ced1) gene from Butyrivibrio fibrisolvens H17c cloned in Escherichia coli. AB - The nucleotide sequence of a 2.314 kb DNA segment containing a gene (ced1) expressing cellodextrinase activity from Butyrivibrio fibrisolvens H17c was determined. The B. fibrisolvens H17c gene was expressed from a weak internal promoter in Escherichia coli and a putative consensus promoter sequence was identified upstream of a ribosome binding site and a GTG start codon. The complete amino acid sequence (547 residues) was deduced and homology was demonstrated with the Clostridium thermocellum endoglucanase D (EGD), Pseudomonas fluorescens var. cellulosa endoglucanase (EG), and a cellulase from the avocado fruit (Persea americana). The ced1 gene product Ced1 showed cellodextrinase activity and rapidly hydrolysed short-chain cellodextrins to yield either cellobiose or cellobiose and glucose as end products. The Ced1 enzyme released cellobiose from p-nitrophenyl-beta-D-cellobioside and the enzyme was not inhibited by methylcellulose, an inhibitor of endoglucanase activity. Although the major activity of the Ced1 enzyme was that of a cellodextrinase it also showed limited activity against endoglucanase specific substrates [carboxymethylcellulose (CMC), lichenan, laminarin and xylan]. Analysis by SDS polyacrylamide gel electrophoresis with incorporated CMC showed a major activity band with an apparent Mr of approximately 61,000. The calculated Mr of the ced1 gene product was 61,023. PMID- 2250657 TI - Expression of the blasticidin S deaminase gene (bsr) in tobacco: fungicide tolerance and a new selective marker for transgenic plants. AB - Blasticidin S (BS), a fungicide of microbial origin, is used for the practical control of rice blast disease. It has broad antimicrobial activity but occasionally exhibits adverse phytotoxic effects on some dicot plants. An inactivating enzyme, BS deaminase, was discovered in the BS resistant strain, Bacillus cereus K55-S1, and the structural gene, bsr, for the enzyme has been cloned. We introduced the bsr gene into tobacco plants using the Ti plasmid vector system and demonstrated that the bsr gene conferred a BS resistant phenotype to the plants. Thus the bsr gene could be useful as a selective marker for plant transformation and provides an example for a new approach to the solution of phytotoxicity problems associated with the use of some types of fungicide. PMID- 2250658 TI - Construction of expression vectors for the gram-negative bacterium Zymomonas mobilis. AB - A set of vectors was constructed for the cloning and expression of heterologous genes in the Gram-negative bacterium Zymomonas mobilis under the control of the pdc promoter of Z. mobilis. The vectors pPTZ1, pPTZ3, and pPTZ4 are based on the cryptic Z. mobilis plasmid pZM02 and on parts of the Escherichia coli plasmids pKK223-3 and pBR322 together with the multiple cloning site of phage M13mp18. DNA fragments can be readily inserted immediately downstream from the pdc promoter at unique restriction sites for KpnI, XbaI and PstI in pPTZ1 and additionally for SmaI and BamHI in pPTZ3. In pPTZ4, the 5' terminal codons of pdc were deleted allowing the formation of gene fusions. Expression of a promoterless chloramphenicol acetyltransferase gene (cat) controlled by the pdc gene promoter resulted in enzyme activities of up to 5.5 U/mg total cell protein in Z. mobilis cells. PMID- 2250659 TI - Magnification of the rDNA cluster in Kluyveromyces lactis. AB - By employing pulsed field gel electrophoresis we find that slow growing strains of Kluyveromyces lactis have only 43%-55% of the wild-type level of ribosomal DNA (rDNA) repeats. When subjected to prolonged vegetative growth these strains can increase both the number of rDNA repeats and their growth rate. PMID- 2250660 TI - Cloning and nucleotide sequence of the Salmonella typhimurium pepM gene. AB - The pepM gene coding for a methionine-specific aminopeptidase was cloned from Salmonella typhimurium and its nucleotide sequence determined. The gene encoded a 264 amino acid protein that was homologous to a similar protein from Escherichia coli. The sequence of an overproducer mutant allele, pepM100, contained a single base change in the likely--35 region of the pepM promoter that increased its homology to the consensus promoter sequence. A region downstream from the pepM coding sequence contained extensive inverted repeats and was homologous to sequences found elsewhere in both Salmonella and other bacterial species. PMID- 2250661 TI - Integration host factor bends the DNA in the Escherichia coli ilvBN promoter region. AB - Integration host factor (IHF) of Escherichia coli is a site-specific DNA binding protein involved in a wide variety of physiological activities in E. coli and its phages and plasmids. We have previously found that IHF binds specifically to a site just upstream from the ilvBN promoter and strongly decreases transcriptional pausing and termination in the ilvBN leader. In this work we show by gel retardation analysis that IHF binds to bent ilvBN DNA and greatly enhances the bend located within or near the IHF binding site. These data are consistent with the hypothesis that IHF-induced alterations in the conformation of ilvBN promoter leader DNA is a key to its antitermination activity in this system. PMID- 2250662 TI - Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells. AB - We have carried out an extensive pharmacological characterization of muscarinic binding sites in rabbit lung and chicken heart in parallel with M1, M2, and M3 sites, [3H]Pirenzepine, a selective antagonist at M1 receptors, bound saturably and reversibly to membranes from chicken heart and rabbit lung. These binding sites were not M1 receptors, however, because the cardioselective antagonist himbacine had 10-fold higher affinity at these sites than at [3H]pirenzepine sites in rat and rabbit cortex (true M1 sites). We measured the inhibitory potency of 28 antagonists at [3H]N-methylscopolamine-labeled sites in chicken heart, rabbit lung, rat heart (M2 sites), and rat submandibular gland (M3 sites) and at M1 sites in rat cortex. The sites in rabbit lung were different from M1, M2, and M3 sites, because they had moderate to high affinity for M1-selective compounds (pirenzepine and telenzepine), M2-selective compounds (himbacine and methoctramine), and M3-selective compounds (hexahydrosiladifenidol and 4 diphenylacetoxy-N-methylpiperidine methiodide). The sites in chicken heart resembled most those in rabbit lung, with similar high affinity for secoverine, but they were not the same because tropicamide, diphenylacetoxybutynyl dimethylamine, and [3H]-N-methylscopolamine were more potent in rabbit lung. In a further series of experiments, we compared the affinity of six of the most discriminating antagonists in membranes from rabbit lung and NG108-15 cells, a neuroblastoma-glioma cell line reported to express the muscarinic m4 receptor gene. The antagonists had very similar affinities in the two tissues, the largest discrepancy being that pirenzepine was twice as potent in rabbit lung as in NG108 15 cells. Northern blots using probes designed to discriminate between five species of muscarinic receptor RNA detected only m4 mRNA in rabbit lung. We conclude that rabbit lung contains a muscarinic M4 binding site with a quite distinctive pharmacology and that chicken heart contains a receptor with similarities to the M4 sites. This is the first report to characterize native M4 binding sites in a nonneuronal mammalian tissue. PMID- 2250663 TI - Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. AB - Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3 methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation. PMID- 2250664 TI - Regulation of guinea pig ileal electrolyte transport by M3-muscarinic acetylcholine receptors in vitro. AB - To determine the muscarinic receptor subtype mediating guinea pig ileal mucosal electrolyte secretion, we compared the potencies (Kb) of selective M1 (pirenzepine) (PZ), M2 (AF-DX 116, methoctramine), and M3 [4-diphenylacetoxy-N methylpiperidine methiodide (4-DAMP), hexahydrosiladifenidol (HHSiD)] antagonists as inhibitors of carbachol-induced reductions in guinea pig atrial heart rate and ileal longitudinal muscle contractions, responses mediated by M2 and M3 receptors, respectively. Pretreatment with all five muscarinic antagonists shifted the carbachol concentration-response curve to the right, in a manner suggesting competitive antagonism. The following affinity profiles (Kb, nM) were obtained for: 1) ileal mucosa: 4-DAMP (2.7) greater than HHSiD (23.0) greater than PZ (110) greater than or equal to methoctramine (395) greater than AF-DX 116 (784); 2) atrial heart rate: 4-DAMP (9.5) congruent to methoctramine (11) greater than AF-DX 116 (63) greater than HHSiD (222) greater than PZ (256); and 3) ileal longitudinal muscle: 4-DAMP (3.1) greater than HHSiD (21) greater than PZ (143) greater than methoctramine (388) greater than or equal to AF-DX 116 (482). The selectivity profiles of these antagonists suggest that muscarinic receptors in the ileal mucosa more closely resemble those in the ileal muscle (M3) than those in atrial muscle (M2). Moreover, M1-muscarinic receptors appear to be relatively unimportant in mediating the effects of carbachol on short circuit current (ISC). Carbachol-induced increases in ISC were also unaffected by pretreatment with 0.5 microM tetrodotoxin, suggesting that electrolyte transport in the guinea pig ileal mucosa may be mediated, in part, by postsynaptic M3-muscarinic receptors on the enterocytes. PMID- 2250665 TI - Direct effects of thymopentin (Arg-Lys-Asp-Val-Tyr) on cholinergic agonist induced slow inactivation of nicotinic acetylcholine receptor function. AB - The effects of thymopentin (TP-5) on the cholinergic agonist-induced inactivation of function (desensitization) of the nicotinic acetylcholine receptor (nAChR) were explored using two systems, 1) Torpedo californica electroplax nAchR reconstituted into phospholipid vesicles and 2) T. californica nAChR expressed, in Xenopus laevis oocytes, from in vitro synthesized RNA transcripts. The pentapeptide did not modify the equilibrium binding of 125I-alpha-bungarotoxin, but toxin rate binding assays in the presence of the cholinergic agonist carbamylcholine (Carb) revealed that it shortened the time course of the Carb induced nAchR transition to the high affinity, desensitized state. Thymopentin (but not thymosins alpha 1 and beta 4) accelerated the slow inactivation of nAchR mediated 86Rb+ influx, as measured by the first-order decrease in the Carb induced 86Rb+ transport into the reconstituted vesicles. The decay of the acetylcholine-induced current from Torpedo receptor expressed in oocytes was also accelerated by TP-5. The pentapeptide had no ion channel-blocking or agonist activity of its own and exhibited a requirement for Ca2+ to express its effects. On the basis of these results, it is proposed that TP-5 has a direct effect on the nAChR, resembling that of noncompetitive blockers, as opposed to an indirect mechanism of action via the activation of specific metabolic pathways. PMID- 2250667 TI - Structure-activity relationships for enhancement of adenosine A1 receptor binding by 2-amino-3-benzoylthiophenes. AB - The structural requirements for stimulation of adenosine A1 agonist binding by 2 amino-3-benzoylthiophenes and related compounds were investigated. Slowing of the dissociation of [3H]N6cyclohexyladenosine binding was used as a specific measure of the allosteric effects of these compounds. The thiophene ring could be replaced with benzene but not with several nitrogen-containing heterocycles. The 2-amino group was required, and at least one hydrogen on the amino group appeared to be necessary for activity. The keto carbonyl was also essential. Alkyl substitution at the 4-position of the thiophene ring increased activity, whereas 5-position substitution appeared to have little effect. Activity was also increased by various substitutions on the phenyl ring, with 3-(trifluoromethyl) showing optimal activity. The phenyl ring could be replaced with cyclohexyl without major loss of activity. 1-Aminofluoren-9-one, a conformationally locked derivative, was active. Based in part in the latter observation, the active conformation is proposed to have an intramolecular hydrogen bond between the amino nitrogen and the carbonyl oxygen. Because the 2-amino-3-benzoylthiophenes showed competitive adenosine antagonism as well as allosteric enhancement, their affinities as competitive inhibitors of [3H]8-cyclopentyl-1,3-dipropylxanthine binding to A1 receptors were also assessed. Structure-activity relationships for competitive antagonism were distinct from those for allosteric enhancement, with ratios between the two activities varying by more than 1000-fold. Of the analogs tested, (2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone (PD 81,723) had the most favorable ratio of enhancement to antagonism. PMID- 2250666 TI - Cellular metabolism of 3'-azido-2',3'-dideoxyuridine with formation of 5'-O diphosphohexose derivatives by previously unrecognized metabolic pathways for 2' deoxyuridine analogs. AB - 3'-Azido-2',3'-dideoxyuridine (AzdU, CS-87) is a potent inhibitor of human immunodeficiency virus replication in human peripheral blood mononuclear cells (PBMC) with limited toxicity for human bone marrow cells (BMC). In the present study, metabolism of AzdU was investigated in human PBMC and BMC after exposure of cells to 2 or 10 microM [3H]AzdU. 3'-Azido-2',3'-dideoxyuridine-5' monophosphate (AzdU-MP) was the predominant metabolite, representing approximately 55 to 65% of intracellular radioactivity in both PBMC and BMC at all times. The AzdU-5'-diphosphate and -5'-triphosphate intracellular levels were 10- to 100-fold lower than the AzdU-MP levels and, of note, AzdU-5'-triphosphate was not detected in human BMC. Using anion exchange chromatography, a new peak of radioactivity, distinct from any known anabolites, was detected. This chromatographic peak was found to be resistant to alkaline phosphatase but was hydrolyzed by 5'-phosphodiesterase, yielding AzdU-MP. Incubation of [3H]AzdU and D-[1-14C]glucose in PBMC and BMC produced a double-labeled peak with the same retention time as the anabolite, suggesting formation of a hexose derivative of AzdU. A novel high performance liquid chromatography method was developed that allowed for the separation of nucleosides, nucleotides, and carbohydrate derivatives thereof. Using this highly specific method, the putative AzdU-hexose actually was separated into two chromatographic peaks. These novel metabolites were identified as 3'-azido-2',3'-dideoxyuridine-5'-O-diphosphoglucose and 3' azido-2',3'-dideoxyuridine-5'-O-diphospho-N-acetylglucosamine. Following 48 hr of incubation with [3H] AzdU, as much as 20 and 30% of these AzdU metabolites accumulated in PBMC and BMC, respectively. When AzdU was removed from the cell cultures, intracellular AzdU diphosphohexose concentrations decayed in a monophasic manner, with an elimination half-life of 14.3 hr. By 48 hr, levels of 0.3 pmol/10(6) cells were still detected, reflecting a gradual anabolism of these metabolites. Elimination of AzdU-MP and AzdU-5'-diphosphate was characterized by a two-phase process, with a short initial half-life of 0.83 and 0.24 hr and a long terminal half-life of 14.10 and 8.24 hr, respectively. Similar diphosphohexoses of deoxyuridine (dUrd) were also detected in human PBMC and BMC after exposure to [3H]dUrd, suggesting that dUrd derivatives are metabolized in a similar manner. In summary, the discovery of novel metabolic pathways for dUrd analogs demonstrates that AzdU has unique metabolic features that may contribute to the low toxicity of this anti-HIV agent in human BMC and also affect its mechanism of action.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2250669 TI - [Genus-specific DNA probe for detection of Yersinia]. AB - In order to create a rDNA probe for plague agent (Yersinia pestis) double stranded DNA fragments complementary to 5'-region of 16S rRNA were synthetized with the help of reverse transcriptase. The fragments were cloned into plasmid vector pUC19 in Escherichia coli. To select plasmids with specific for Y. pestis sequences, recombinant clones and plasmids purified from them were cross hybridized to [gamma-32 P]-labelled 16S rRNA of E. coli and Y. pestis. As was shown after sequencing of recombinant plasmids, those that did not hybridize to 16S rRNA of E. coli carried a DNA copy of variable region V1 of Y. pestis 16S rRNA. This region was used as a basis for the construction of rDNA probe for genus-specific determination of Yersinia. PMID- 2250668 TI - Ethanol potentiates oxygen uptake and toxicity due to menadione bisulfite in perfused rat liver. AB - Menadione bisulfite is a hepatotoxicant that damages periportal regions of the lobule in perfused liver in an oxygen-dependent manner. The effect of ethanol on menadione bisulfite toxicity was examined in perfused rat liver. Addition of menadione bisulfite (3 mM) alone to the perfusate increased oxygen uptake by 20 30 mumols/g/hr. Lactate dehydrogenase was released into the effluent after 60 min of perfusion and reached values around 100 units/g/hr. Under these conditions, trypan blue was taken up exclusively in periportal regions of the liver lobule; 44% of periportal cells were stained. In the presence of ethanol, maximal increases in oxygen uptake due to menadione bisulfite were much larger (about 90 mumols/g/hr), and lactate dehydrogenase release occurred earlier and reached higher maximal values (330 units/g/hr). Trypan blue staining was also more extensive; 90% of periportal cells were stained. The effect of ethanol on menadione bisulfite-induced oxygen uptake required metabolism via alcohol dehydrogenase (ADH), because ethanol increased oxygen uptake due to menadione bisulfite from 44 to 81 mumols/g/hr in deermice with ADH but had no effect in deermice lacking ADH. Other agents that increase NADH (xylitol and 2-ethyl-1 hexanol) also potentiated the stimulation of oxygen uptake due to menadione bisulfite, suggesting that ethanol was working by increasing the NADH redox state. Cyanide abolished the increase in oxygen uptake due to menadione bisulfite, both in the absence and in the presence of ethanol, supporting the hypothesis that the effect of ethanol on menadione bisulfite-mediated oxygen uptake involves the mitochondrial respiratory chain. Further, the stimulation of oxygen uptake by menadione bisulfite in isolated mitochondria was enhanced when matrix NADH was increased by addition of beta-hydroxybutyrate. These data indicate that ethanol potentiates oxygen uptake and toxicity due to menadione bisulfite most likely by generation of NADH for redox cycling of this model quinone. PMID- 2250670 TI - [Comparative analysis of the structure of SUP2 genes in Pichia pinus and Saccharomyces cerevisiae]. AB - SUP2(SUP35) is an omnipotent suppressor gene, coding for an EF-1 alpha-like protein factor, involved in the control of translational accuracy in yeast Saccharomyces cerevisiae. A SUP2 gene analogue from yeast Pichia pinus was isolated by complementation of temperature-sensitive sup2 mutation of S. cerevisiae. Nucleotide sequence of the SUP2 gene of P. pinus codes for a protein of 82.4 kDa exceeding the SUP2 protein of S. cerevisiae for 6 kDa. The SUP2 gene product of P. pinus is similar to the Sup2 protein of S. cerevisiae by its structure and includes a highly conservative (76%) C-terminal region homologus to EF-1 alpha and a lowly conservative N-terminal region. The relation between the evolutionary conservativity of different regions of the Sup2 protein and their functional significance is discussed. PMID- 2250671 TI - [Deletion analysis of the SUP2 gene in Saccharomyces cerevisiae]. AB - The sup2 mutations of the yeast Saccharomyces cerevisiae or plasmid-mediated amplification of the wild type SUP2 gene lead to suppression of different types of nonsense mutations. The Sup2 protein includes a C-terminal region homologous to elongation factor EF-1 alpha and an unique N-terminal region. The SUP2 is an essential gene. The functional role of different regions of the SUP2 gene was investigated, by deleting them without disruption of the reading frame. Such constructs were maintained in yeast on episomal or centromeric plasmids. It was shown that the region, homologous to EF-1 alpha is necessary for viability, while the remaining N-terminal part is nonessential. The region of the first 154 amino acids is necessary and sufficient for the suppressor effect, caused by plasmid mediated amplification of the SUP2 gene. PMID- 2250672 TI - [Specific modification of the alpha-subunit of Escherichia coli Rna polymerase by monomercuric derivative of fluorescein mercuric acetate]. AB - The method for specific modification of Escherichia coli RNA polymerase by a monomercuric derivative of fluorescein--fluoresceinmonomercuracetate (FMMA)--a specific reagent for SH-groups of proteins is suggested. It is shown, that in conditions of equimolar FMMA/enzyme ratio the fluorescent label interacts preferantially with a single sulfhydryl group in alpha-subunit of RNA polymerase. The mercaptide bonding formation is followed by significant alterations of all spectral parameters of FMMA, but has no effect on the kinetic parameters (KB and k2) of RNA synthesis initiation nor does it lead to inhibition of the total RNA synthesis. The modification presented may be used in structural and topological investigations of RNA polymerase functioning. PMID- 2250673 TI - [Activation of transcription function in lymphocytes after irradiation with He-Ne laser]. AB - The influence of He-Ne-laser irradiation (lambda = 632.8 nm) in dose 56 J/m2 on the ultrastructure of the nucleolus from human peripheral lymphocytes was studied electronmicroscopically. After 1 h irradiation a well-expressed reaction of the nucleolus was observed in 70% of the lymphocytes under examination. Changes consist in the appearance of a wrong-shaped fibrillar center or in its fragmentation, the increase of RNP-containing fibrillar and granular components, and also in expansion of vacuoli. In a number of irradiated lymphocytes nucleoli with several fibrillar centres and with a strand-like organization of RNP part were observed. The size of these nucleoli increases. Following the accepted functional interpretations the observed changes can be connected with the intensification of RNA metabolism including the synthesis, processing of pre-rRNA and preribosome transport from the nucleolus. Similar rearrangements of the nucleoli were revealed in parallel experiments with phytohemagglutinin-treated lymphocytes. They were observed 1 h after the stimulation of lymphocytes. Taking into account the absence of mitogenic action of He-Ne-laser irradiation on lymphocytes, the ultrastructural changes of nucleoli under the action of irradiation are considered as functional activation of rRNA synthesis in the Go period. PMID- 2250674 TI - [Characteristics of nonenzymatic binding of oligoribonucleotides-- analogs of mRNA and Phe-tRNA Phe with 80S ribosomes from human placenta]. AB - Binding of labelled oligouridylates--mRNA analogs--to human placenta 80S ribosomes in the presence of Phe-tRNAPhe has been studied. The single site for (pU)n (n = 6, 9, 13) binding on the ribosome was found; association constants for their tRNA-dependent binding were evaluated. In the presence of oligouridylates as templates [14C]Phe-tRNAPhe was found to be able to bind simultaneously at acceptor and donor ribosomal sites which resulted in diphenylalanine formation. The observed maximum Phe-tRNAPhe binding level was considerably lower than for the corresponding oligouridylate binding; the longer oligouridylate the higher Phe-tRNAPhe maximum binding level. To explain the results obtained we have proposed that (i) (Phe)2-tRNA produced from transpeptidation dissociates from the ribosomal A site to a significant extent and (ii) when oligouridylate length increases its interaction with 3'-side of mRNA binding center results in allosteric stabilization of the complex of peptidyl-tRNA with the ribosome at A site. PMID- 2250675 TI - [Interaction of the antineoplastic agent mitoxantrone with double-stranded nucleic acids]. AB - The binding of mitoxantrone with double-helical nucleic acids was investigated by the methods of isothermal microcalorimetry, circular dichroism and absorption at the ionic strength mu = 0.11 and 0.011 M NaCl at temperature region of 30 divided by 60 degrees C. The investigation shows, that at mu = 0.11 M NaCl mitoxantrone interacts with double-helical nucleic acids in one way only. For such conditions using spectrophotometric titration data Scatchard plots for the binding of mitoxantrone with double-helical nucleic acids were constructed. The calculations show that the saturation stoichiometry is one mitoxantrone molecule per 2 divided by 3 base pairs DNA and 6 divided by 8 base pairs RNA. The dependence of binding constant from GC-content is observed. It is shown that the binding enthalpy of mitoxantrone with DNA and RNA increases linearly and reaches -(3.0 +/- 0.5) kkal per 1 mol mitoxantrone. It is shown that a binding mitoxantrone with double helical nucleic acids, besides the intercalation of rings, a determinate contribution in the binding is given also by electrostatic interaction of side chains mitoxantrone with nucleic acids. PMID- 2250676 TI - [Economical sequencing of DNA with terminators]. AB - We describe several improvements of chain-termination DNA sequencing procedure of Sanger et al. For template preparation we use 0.3 ml cultures of M13 clones, grown in standard 1,5 ml polypropylene tubes. The sequencing experiment differs from the previously described by the use of deoxyNTP, labelled with phosphorus-33 (a low energy isotope with a half-life of 25 days, commercially produced in the USSR), and by a "quasi-end labelling" reaction, preceding the DNA synthesis in the presence of dideoxyNTPs. The combination of the phosphorus-33 and the quasi end labelling produces very sharp sequencing ladders, that equal or exceed in quality those obtained with sulphur-35, and only an overnight exposure with a conventional X-ray film is required. The use of plastic tubes for bacterial growth and the 60-well microchambers for carrying out sequencing reactions results in substantial saving of time and cost in routine "middle scale" sequencing (both types of plasticware are produced in the USSR). PMID- 2250677 TI - [Identification of the glucocorticoid receptor binding site at the 5'-flanking region of mouse metallothionein I gene: the effect of base substitutions on binding efficiency]. AB - Interaction of highly purified glucocorticoid receptor complex (GIRC) with synthetic DNA-fragment of mouse metallotionein 1 gene promoter from -209 to -252 b.p. (MTwt) was investigated. By means of nitrocellulose filter binding assay this fragment was shown to contain specific GIRC-binding site. In order to analyse the fine structure of the site, two variants of this DNA-fragment were synthesized and used in gel retardation assay. GIRC specific binding was shown to retain throughout interaction with the fragment in which all base pairs in the surroundings of generally accepted GIRC-binding site consensus G--ACA---TGTTCT C- TGT---ACAAGA were substituted by means of transitions, but it was weaker than the GIRC-binding with MTwt, where the mentioned consensus was situated in the natural surroundings. Complete loss of the GIRC-binding ability was observed when five CG pairs were substituted by AT ones. Two of the CG pairs belonged to the mentioned consensus. Comparison of the data obtained with results of computer analysis allows to consider the consensus as a "core" of GIRC-binding site, flanked with additional elements, interacting with GIRC. PMID- 2250678 TI - [Prediction of protein conformation using a doublet code method]. AB - It is suggested that regions of irregular structure, beta-structure, and alpha helix are composed of 2, 3, and 5 amino acid residue long elements (structurons), respectively, and that the structurons are encoded solely by residue pairs (doublet codons) (i, i + 1), (i, i + 2), (i, i + 4), respectively. Tables of codons are obtained by statistical analysis of the data on the distribution of these pairs in available secondary structures of 62 proteins. These tables are used to obtain distributions of t-, beta- and alpha-codons for an amino acid sequence of protein. When codons of different structures superpose, that is, include the same sequence regions, selection is performed, the selection being performed so to obtain as much as possible number of the non-superposed codons of different structures. The distributions of structurons obtained after this selection are used for localization of structurons in the sequence and prediction of secondary structure on the basis of this localization. The prediction method is illustrated. An accuracy of the method has been tested on the basis an casual selection of fifteen proteins and found equal 64% for secondary structure on the whole and 79%, 53%, 61% for alpha-helix, beta-structure and coil respectively. This result is similar or better than that communicated for contemporary methods. PMID- 2250680 TI - [Fish pituitary gonadotropins. Characteristics of salmon gonadotropic hormones]. AB - This review presents an attempt to systematize the fish gonadotropin investigations data, particularly concerning salmons. The common characterization of pituitary glycoprotein hormones of Vertebrata is presented. A brief review of the history of investigating fish gonadotropins is given. Immunological properties, subunit composition, carbohydrate component and gonadotropin receptors are described. The sequence data comparison and analysis are presented. PMID- 2250679 TI - [The nature of N-terminal signal sequence determines the type of intracellular distribution and effectiveness of export of human growth hormone in Saccharomyces cerevisiae]. AB - Various N-terminal signal peptides (SP) were tested to investigate a human growth hormone (hGH) synthesis, processing and intracellular sorting in yeast. Maximal level of hGH was observed in the case when the mature hGH gene was placed under the control of PHO5 promoter. In this case about 90% of hGH was localized in the cytosol, but some portion was trustworthly detected in microsomes and periplasma in spite of the absence of SP. Addition of own or PHO5 SP resulted in lowering of the synthesis and a difficulty in the prehGH processing. In this case the immunoreactive products were localized mainly in periplasma and vacuoles and to a lesser degree in the cytosol. When hGH gene was placed under the control of the yeast MF alpha 1 promoter and alpha-factor preprosegment was used as SP more then a half (67%) of hGH processed correctly was exported in a medium, the rest was detected in vacuole (17%) and periplasma (8%). PMID- 2250681 TI - [Transforming growth factor beta--a new type of inhibitor of proliferation of normal and tumor cells]. AB - Based on literature data and on the results of the authors' investigation, the analysis of the transforming growth factor beta action as an inhibitor of proliferation of normal and tumor cells was carried out. The possible mechanisms of modulation of this action by other growth factors and by the cultivation conditions were considered. An attempt was made to determine the role of the transforming growth factor beta in the system of regulators of cell proliferation on the early stages of ontogenesis and during carcinogenesis. PMID- 2250682 TI - [Enhancers, DNA loops and stable complexes: a mechanism of transcription activation]. AB - A recurrent theme in molecular biology is that of "action at a distance" along DNA. We consider various mechanisms of action of transcriptional enhancers as a well-characterised example of interaction between widely separated DNA-bound proteins. The role of promoter- and enhancer-binding proteins in the formation of a stable promoter complex, and the mechanisms of interaction between multiple activatory DNA sequences is also discussed. PMID- 2250683 TI - [The use of monoclonal antibodies against insulin for isolation of proteins inhibiting the cell growth]. AB - Extracts of pig kidneys or germinated soya beans after preliminary steps were affinity chromatographied on Sepharose containing cyanogen bromide immobilized monoclonal antibodies to pig insulin. The material bound to the affinity column was separated by HPLC resulting in one homogeneous protein from each source. Both proteins have been shown to inhibit DNA synthesis in cultured embryonic human fibroblasts and VERO fibroblasts. The effect of pig kidney protein was potentiated by insulin. Soya and pig proteins were characterized by the following parameters: molecular weights of 8.5 and 10.3 kD, apparent constants of dissociation with rat liver plasma membranes of 4.7 x 10(-8) M and 9.8 X 10(-8) M, respectively. The soya proteins competed for the binding sites on plasma membranes with insulin whereas the pig protein did not. The N-terminal amino acid sequences of 20 residues were determined for both proteins. Comparison of these sequences with known protein sequences was performed. A 30-40% primary structure homology of the studied fragment of soya bean protein with the fragments of some oncogenic viruses proteins and transforming proteins was revealed. PMID- 2250684 TI - [Molecular-biological study of vaccinia virus genome. I. Cloning of vaccinia virus DNA fragments in bacterial vectors]. AB - The HindIII DNA fragments of vaccinia virus strain L-IVP were cloned in pBR322 bacterial plasmid. A hybrid plasmids collection of pVHn series contains all fragments of virus genome except terminal HindIII-B and HindIII-G, and also a large HindIII-A. The latter was cloned in cosmid pHC79. The obtained collection of hybrid DNA molecules allows to carry out a wide range of molecular biological experiments on the vaccinia virus genome. PMID- 2250685 TI - [Molecular-biological study of vaccinia virus genome. II. Localization and nucleotide sequence of vaccinia virus genes coding for proteins 36K and 12K]. AB - Genes encoding virus-specific late proteins with molecular mass 36 kDa and 12 kDa were mapped in HindIII-P DNA fragment of vaccinia virus strain L-IVP by hybrid selection of RNA to cloned DNA fragments followed by in vitro translation. RNA origin site of the 36K protein was detected in HindIII-J fragment. Nucleotide sequences of these genes were determined. Amino acid sequences of the 36K and 12K polypeptides were compared with the protein bank PIR. PMID- 2250686 TI - [Molecular-biological study of vaccinia virus genome. III. Identification of the late gene product protein 36K from Hind-III-P-fragment of vaccinia virus strain L IVP]. AB - Vaccinia virus gene encoding 36K protein was cloned in pUR290 bacterial expressing vector and resulted in the synthesis of a chimeric protein in E. coli. The chimeric protein consists of beta-galactosidase and virus protein in C termini. It has virus antigen specificity. By monospecific antibody 36K protein of vaccinia virus was determined to be non-virion. It is localized in the cytoplasm of infected cells. PMID- 2250687 TI - Calcium uptake and efflux during the yeast to mycelium transition in Sporothrix schenckii. AB - A study was made of calcium metabolism during germ tube formation in Sporothrix schenckii yeast cells. A net efflux of calcium was observed very early in the transformation process and remained constant thereafter. The efflux of calcium in yeast cells induced to form germ tubes was twice that observed in yeast cells not induced to form germ tubes. Two peaks of calcium uptake were observed in germ tube forming yeast cells at 30 and 300 minutes following inoculation, while non induced yeast cells, a continuous increase in uptake was observed which ultimately reached higher values than the ones obtained in germ tube forming cells. Substances which affect calcium metabolism in other cells such as cobalt ions, ionophore A23187 and compound R24571 were observed to inhibit germ tube formation and calcium uptake. In addition, ionophore A23187 was found to increase calcium efflux to approximately twice the control values. The inhibition of germ tube formation brought about by substances which inhibit calcium uptake or increase efflux suggests that the intracellular calcium concentration in these cells must be precisely regulated for the yeast to mycelium transition to occur. PMID- 2250688 TI - A murine model for the study of the impact of Aspergillus fumigatus inoculation on the foeto-placental unit. AB - Pregnant female BALB/c mice were inoculated intravenously with Aspergillus fumigatus conidia in different concentrations (1 x 10(1)-1 x 10(8)) on day 10 of pregnancy. Pregnancy was confirmed by the presence of murine alpha-fetoprotein (m AFP) in the maternal circulation. Conidia inoculation of 1 x 10(3) and greater significantly (p less than 0.0001) resulted in abortion or placental lesions. Uterine cell infiltrations were recognized in 75% of the mice which aborted following the inoculation of 1 x 10(3) conidia or more. In the placental lesions of mice inoculated with 0.5-1 x 10(8) conidia, hyphae, haemorrhage, thrombosis, necrosis, calcification, and inflammation were regular findings. Histopathology of other maternal organs revealed that extrauterine organ lesions were closely correlated with the dose of conidia inoculated, and the following pattern of reaction was found: liver greater than lung greater than kidney greater than brain greater than heart. PMID- 2250689 TI - A case of sporotrichosis caused by two genetically different Sporothrix schenckii strains. AB - Two Sporothrix schenckii strains of different mitochondrial DNA restriction profiles were isolated from different cutaneous lesions in a 53 year-old woman with sporotrichosis. These results suggest that sporotrichosis can be simultaneously caused by two or more genetically different S. schenckii strains. PMID- 2250690 TI - Isolations of dermatophyte from clinically normal scalps in M. canis infections using the hairbrush method. AB - The scalp hair of patients with dermatophytosis due to M. canis but without scalp lesions, and that of their family members without dermatophytosis were examined using the hairbrush method. The dermatophyte was detected in 93.8% of the scalps of those who lived in homes where cats were kept, and in 25% of those without cats. After the source of infection had been treated, the dermatophyte showed a gradually decreasing presence, finally disappearing altogether, so that no case of the disease on the scalp hair could be found. We inferred from the above findings in M. canis infections that, since the dermatophytes are seen in a high proportion of cases without scalp lesions, the dermatophytes, in many cases, exist only as saprophytes on the hair. PMID- 2250692 TI - Cryptococcus neoformans var. gattii in a Brazilian AIDS patients. PMID- 2250693 TI - Research Lobbying: researchers fight for a voice. PMID- 2250691 TI - Polyamine depletion and growth inhibition of Cryptococcus neoformans by alpha difluoromethylornithine and cyclohexylamine. AB - The ability of two known inhibitors of polyamine synthesis alpha difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and cyclohexylamine, an inhibitor of spermidine synthase, to inhibit the in vitro growth and polyamine synthesis of clinical isolates of Cryptococcus neoformans was examined. Treatment of C. neoformans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth. Cryptococcus neoformans was shown to lack detectable spermine and to require high concentrations of spermidine, but not putrescine, for growth. The growth inhibition by DFMO and cyclohexylamine was reversed by exogenous polyamines. These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important isolates of C. neoformans. PMID- 2250694 TI - Scientific publishing: pressure for quick release. PMID- 2250695 TI - Radiation exposure: lower dose limits. PMID- 2250696 TI - Sexual lifestyles under scrutiny. PMID- 2250697 TI - The testing of laetrile. PMID- 2250698 TI - Cohort of genes. PMID- 2250699 TI - Why become complicated? PMID- 2250701 TI - Insulin signalling: search for the missing links. PMID- 2250700 TI - The new biology of immune recognition. PMID- 2250702 TI - Evolution: living fast and dying young. PMID- 2250703 TI - Influence of colour on the perception of coherent motion. AB - We have colour vision because there are three types of cone photoreceptors which are maximally sensitive in the long (L), middle (M) and short (S) wavelength regions of the spectrum. Psychophysical experiments have, however, revealed mechanisms selectively responsive to light modulated in three 'cardinal directions' in colour space. The responses of these mechanisms are determined by algebraic sums of the excitations of the cones. One of these mechanisms is responsive to changes in luminance, its spectral sensitivity being that of the sum of the L and M cones. The other two respond best to isoluminant changes in light. The responses of one of these mechanisms are determined by the difference in the excitations of the L and M cones, and those of the other one determined by the difference between the excitation of the S cones on the one hand and the excitations of the L and M cones on the other. We have obtained quite surprising results concerning the role of these mechanisms in the perception of motion. Drifting gratings modulated along different cardinal directions appear to slip with respect to one another. In contrast, when the directions of the modulations are rotated by 45 degrees in colour space, the gratings cohere. Our results are consistent with the notion that information about movement is analysed within mechanisms maximally responsive along the cardinal directions. PMID- 2250704 TI - Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. AB - The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B cell lymphomas. The bcl-2 gene product is not altered by the translocation, but its expression is deregulated, presumably by the Igh enhancer E mu. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress and thereby confer a growth advantage. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro but do not show a propensity for spontaneous tumorigenesis. In contrast, an analogous myc transgene, designed to mimic the myc-Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. E mu-bcl-2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than E mu myc mice. Suprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell. PMID- 2250705 TI - Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. AB - The t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein. Transgenic mice bearing a bcl-2 immunoglobulin minigene demonstrate a polyclonal expansion of resting yet responsive IgM-IgD B cells which display prolonged cell survival but no increase in cell cycling. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation. By using immunolocalization studies we now demonstrate that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k). Overexpression of Bcl-2 blocks the apoptotic death of a pro-B-lymphocyte cell line. Thus, Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and interfering with programmed cell death independent of promoting cell division. PMID- 2250706 TI - Loss of photosynthetic and chlororespiratory genes from the plastid genome of a parasitic flowering plant. AB - Photosynthesis is the hallmark of plant life and is the only plastid metabolic process known to be controlled by plastid genes. The complete loss of photosynthetic ability, however, has occurred on several independent occasions in parasitic flowering plants. Some of these plants are known to lack chlorophyll and certain photosynthetic enzymes, but it is not known to what extent changes have occurred in the genes encoding the photosynthetic apparatus or whether the plants even maintain a plastid genome. Here we report that the nonphotosynthetic root parasite Epifagus virginiana has a plastid chromosome only 71 kilobases in size, far smaller than any previously characterized land plant plastid genome. The Epifagus plastid genome has lost most, if not all, of the 30 or more chloroplast genes for photosynthesis and most of a large family of plastid genes, the ndh genes, whose products may be involved in a plastid respiratory chain. The extensive changes in Epifagus plastid gene content must have occurred in a relatively short time (5-50 x 10(6) yr), because Striga asiatica, a related photosynthetic parasite, has a typical complement of chloroplast genes for photosynthesis and chlororespiration. The plastid genome of Epifagus has retained transcribed ribosomal RNA and ribosomal protein genes, suggesting that it expresses one or more gene products for plastid functions not related to photosynthesis. PMID- 2250707 TI - Force generation of organelle transport measured in vivo by an infrared laser trap. AB - Organelle transport along microtubules is believed to be mediated by organelle associated force-generating molecules. Two classes of microtubule-based organelle motors have been identified: kinesin and cytoplasmic dynein. To correlate the mechanochemical basis of force generation with the in vivo behaviour of organelles, it is important to quantify the force needed to propel an organelle along microtubules and to determine the force generated by a single motor molecule. Measurements of force generation are possible under selected conditions in vitro, but are much more difficult using intact or reactivated cells. Here we combine a useful model system for the study of organelle transport, the giant amoeba Reticulomyxa, with a novel technique for the non-invasive manipulation of and force application to subcellular components, which is based on a gradient force optical trap, also referred to as 'optical tweezers'. We demonstrate the feasibility of using controlled manipulation of actively translocating organelles to measure direct force. We have determined the force driving a single organelle along microtubules, allowing us to estimate the force generated by a single motor to be 2.6 x 10(-7) dynes. PMID- 2250708 TI - Genome project to tackle mass screening. PMID- 2250709 TI - Hungarian research. Luring back the exiles. PMID- 2250710 TI - BST gets clean bill of health. PMID- 2250711 TI - Investment in UK universities. PMID- 2250712 TI - Immunology. The invariant dating service. PMID- 2250713 TI - Haemoglobin. Molecular inventiveness. PMID- 2250714 TI - Genetics. Evolution of the X chromosome. PMID- 2250715 TI - Computational physics. Of micelles and membranes. PMID- 2250716 TI - Intracellular transport of class II MHC molecules directed by invariant chain. AB - Three structural motifs in the invariant chain (li) control the intracellular transport of class II major histocompatibility complex molecules. An endoplasmic reticulum retention signal in the full-length li suggests a role for li in the alpha-beta heterodimer assembly. Another signal motif directs a truncated li, alone or associated with individual class II chains, to a degradation compartment by a pathway circumventing the Golgi. When this truncated li binds alpha-beta dimers, a third signal dominates, directing the complex by way of the Golgi to vesicles in the cell periphery, which may represent a subcompartment of recycling endosomes. PMID- 2250717 TI - A yeast mitochondrial outer membrane protein essential for protein import and cell viability. AB - The gene encoding ISP42, an integral outermembrane protein located at the yeast mitochondrial protein import site was cloned, sequenced and modified. Yeast cells depleted of ISP42 accumulate uncleaved mitochondrial precursor proteins and then die. ISP42 is the first mitochondrial membrane protein shown to be indispensable for protein import and cell viability. PMID- 2250718 TI - Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. AB - Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The non-obese diabetic mouse is a good spontaneous animal model of the human disease, with IDDM developing in 50-80% of female mice by the age of 6 months. The disease can be transferred by splenic T cells from diabetic donors and is prevented by T-cell depletion. The mechanism(s) by which the beta cell is specifically destroyed is not known, but T cells and macrophages have both been implicated, based on the presence of macrophages in the infiltrated islet and the ability of chronic silica treatment to prevent disease. The monoclonal antibody 5C6 is specific for the myelomonocytic adhesion-promoting type-3 complement receptor (CR3 or CD11b/CD18) and does not bind to T cells. Here we show that blockade of macrophage CR3 in vivo prevents intra-islet infiltration by both macrophages and T cells and inhibits development of IDDM. We conclude that both T cells and macrophages have an essential role in the onset of IDDM. PMID- 2250719 TI - ATP sulphurylase activity of the nodP and nodQ gene products of Rhizobium meliloti. AB - The symbiotic bacterium Rhizobium meliloti stimulates alfalfa (Medicago sativa L.) roots to undergo morphogenesis and form nitrogen-fixing nodules. It has been proposed that the bacterial genes nodABC, common to all Rhizobium, are required for synthesis of an oligosaccharide factor, which is converted to a sulphated form (NodRm-1) by the products of the R. meliloti-specific genes nodH and nodQ1 5; NodRm-1 elicits host-specific plant responses. Previously we have shown that the nodP gene is homologous to a segment of the Escherichia coli genome; when we cloned this E. coli fragment we found that it mapped near 59 minutes, corresponding to the cysDNC locus. The genes cysD and cysN encode proteins that catalyse the synthesis of adenosine 5'-phosphosulphate, the first step in the activation of inorganic sulphate. Here we demonstrate that nodP and nodQ correspond to cysD and cysN, and that their proteins have ATP sulphurylase activity both in vivo and in vitro. We propose that nodP and nodQ synthesize an activated sulphate that is an intermediate in the formation of the alfalfa specific sulphated nodRm-1 factor. PMID- 2250720 TI - Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells. AB - Specific genes can be inactivated or mutated in the mouse germ line. The phenotypic consequences of the mutation can provide pivotal information on the function of the gene in development and maintenance of the mammalian organism. The procedure entails homologous recombination in embryonic stem cells, which, on fusion to recipient blastocysts, give rise to chimaeric mice that can transmit the mutant gene to their offspring. Inbreeding can then yield mice carrying the mutation in both alleles allowing the phenotypic analysis of recessive mutations. In addition to mice lacking a particular gene function, cell lines carrying null alleles of normally expressed genes can be instrumental in assessing the function of the gene. These cell lines can either be obtained from homozygous animals or, should the mutation be lethal early in embryonic development, be generated by consecutive inactivation of both alleles by homologous recombination in cultured cells. Here we illustrate the feasibility of this latter approach by the efficient consecutive inactivation of both alleles of the pim-1 proto-oncogene in embryonic stem cells. PMID- 2250722 TI - Chemiluminescent multiplex DNA sequencing. PMID- 2250721 TI - Evolution of a polymeric globin in the brine shrimp Artemia. AB - Several invertebrate species possess haemoglobins in which each polypeptide contains multiple haem-binding domains, possibly reflecting the fusion of multiple monomeric globin transcriptional units at the gene level. We have now analysed the transcript of such a polymeric globin gene from the brine shrimp Artemia, which expresses three polymeric haemoglobins, each of relative molecular mass 260,000 (Mr 260K). These are formed by the variable association of two different subunit types, alpha and beta (refs 2,3). Haemoglobins I and III are homodimers of alpha and beta subunit types, respectively, and haemoglobin II is a heterodimer (alpha beta). The individual globin chains are of similar size (Mr 130K), but the exact nature of the differences between the two subunit types is unclear. Analysis of complementary DNA clones encoding one of the subunits of the Artemia dimeric haemoglobin showed that the globin messenger RNA encodes nine myoglobin-like domains, connected by linking peptides. The residues in the linkers are characteristic of those found generally in such protein linkers, and include turn-promoting amino acids. Each domain also contains the conserved residues that are required for functional haem-binding, and from analysis of the sequences it was predicted that they all can adopt the classic myoglobin-like fold. Analysis of the derived amino-acid sequences indicated that the individual domains are duplicated monomers that fused to form the polymeric globin some 200 Myr ago. The fusion of multiple transcriptional units for the evolution of a polymeric globin gene may have been a general mechanism for the appearance of such polymeric haemoglobins in invertebrates. PMID- 2250723 TI - [Biochemistry of cellular radiation reactions. An indication for ongoing protective mechanisms against oxidative cell damage]. AB - Cellular radiation, which is the constant low-level photon emission in animal and plant tissue, is due to particular reactions of metabolism producing ultraweak chemiluminescence. A possible effect of the cellular radiation is the activation of DNA photolyases. In most chemiluminescent processes reactive oxygen metabolites are transformed. When these reactions occur in the cytosol they help to protect vital cell structures against oxidative damage. PMID- 2250724 TI - Electron microscope identification of mineral fibers in human lung tissue. PMID- 2250725 TI - Saturation-type exponential function with a deceleration term for calculating nonlinear kinetics. PMID- 2250727 TI - The bronchial diverticula of Xenopus larvae. Are they essential for hydrostatic assessment? PMID- 2250726 TI - Neurons in the midbrain of the barn owl are sensitive to the direction of apparent acoustic motion. PMID- 2250728 TI - The good and bad for Medicare in the FY '91 budget accord. PMID- 2250729 TI - Renal nutrition and the noncompliant patient: some guidelines. PMID- 2250730 TI - HIV testing and transient dialysis. A study undertaken by the Council of Nephrology Social Workers National Kidney Foundation, Inc. AB - A good summation response came from one Southwest facility: "We can't demand a test, but we request it. We haven't had a positive transient yet, but we couldn't legally turn them away...besides, it wouldn't seem right. We've talked about it, even where our own patients are concerned, and we're scared. Even though we use universal precautions, we know we'd treat a positive (HIV) patient differently. We'll have to face it sooner or later." Unfortunately, it appears that such anxieties are frequently leading to testing and subsequent discriminatory barriers. It is important that nephrology organizations continue to advocate for patients' rights and against unfair and prejudicial practices. Realistically, however, individual health care providers and patients are the ones who must risk challenging the system. Social workers are particularly mandated to become involved in this process through ongoing education and discussion and persistent questioning of HIV testing policies. PMID- 2250731 TI - Care of AIDS and/or HIV+ patients requiring dialysis (a positive statement of the Board of Directors and the Medical Review Board, Southern California Renal Disease Council, Inc., ESRD Network #18). PMID- 2250732 TI - ESRD and AIDS: the NKF viewpoint. National Kidney Foundation, Inc. PMID- 2250733 TI - Planning for compliance: OSHA's bloodborne pathogen rule. AB - Overall, the bloodborne pathogen rule constitutes a reasonable response to a significant threat to workplace safety. The risks to dialysis workers from HBV and HIV must be minimized or eliminated and the rule is generally consistent with the consensus approach. Unfortunately for dialysis providers, the rule is not exempt from the law of unintended consequences: government regulation will always have impact beyond its object. Promulgation of the final rule will immediately increase the expenses of dialysis providers. Additionally, the enormity of the HBV and HIV problem coupled with the open-ended nature of the rule's key provisions will almost certainly bring additional costs. So long as dialysis reimbursement remains flat, the unintended consequence of the bloodborne pathogen rule may be to quicken the pace of consolidation in the dialysis service market. The added burden of compliance may be too much for small independent facilities. Only large chains may have the resources to comply and survive. To forestall this effect and to provide employees with maximum protection, all dialysis providers should plan now for compliance. PMID- 2250734 TI - Hypertension and diabetes. PMID- 2250735 TI - Hypertension in the black population--revisited. PMID- 2250736 TI - The National Kidney Foundation: three glimpses of the past. PMID- 2250737 TI - Canadian physicians provide more services for lower fees--Stanford study. PMID- 2250738 TI - The NKF and organ donation: a look at the past 10 years. National Kidney Foundation, Inc. PMID- 2250739 TI - Waking up to HIV. PMID- 2250740 TI - [Psychiatric aspects of the HIV infection]. PMID- 2250741 TI - [Behavior analytic approaches of research in psychiatry]. AB - Biologically oriented psychiatric research usually relies more on abstract nosological concepts than on purely descriptive psychopathological syndromes. However, biological validation of psychiatric diagnoses has not been possible so far. More recent findings emphasize the nosological unspecificity, but syndromal specificity of biological data. It seems promising therefore to differentiate psychopathological descriptions more clearly by using objective methods of behavioural assessment and analysis. Concept, methods and examples of this empirical approach will be outlined. PMID- 2250742 TI - [The so-called "AIDS phobia". Symptoms and diagnostic classification of a current hypochondriacal syndrome in hospitalized psychiatric patients]. PMID- 2250743 TI - [The premorbid development of patients with various forms of psychoses]. PMID- 2250744 TI - [Mental handicap in school age children of Mannheim. An epidemiologic contribution]. PMID- 2250745 TI - [Life support measures versus death with dignity in demented patients. A case report]. PMID- 2250746 TI - [The patient, family and physician on the path to treatment partnership. Case report of a 19 year schizoaffective disease course]. PMID- 2250747 TI - [Temporary "rapid cycling" in bipolar affective psychosis. Autochthonous manifestation or pharmacogenic induction?]. PMID- 2250748 TI - Netherlands Society of General Medicine. Utrecht, 13 December 1989. Abstracts. PMID- 2250749 TI - Annual meeting of the Netherlands Association of Internal Medicine. 29-30 March 1990. Abstracts. PMID- 2250750 TI - Netherlands Society of Gastroenterology. Veldhoven, 23-24 March 1990. Abstracts. PMID- 2250751 TI - Acquired severe aplastic anaemia in adults--a single centre study with 13 years follow-up. AB - Between 1974 and July 1987 the diagnosis of severe aplastic anaemia (SAA) was confirmed in 82 patients. Overall actuarial survival was 57% at 7 yr. Four patients recovered while receiving conventional therapy, and four died before treatment with antithymocyte globulin (ATG) or bone marrow transplantation (BMT) could be initiated. Nineteen patients (median age 19.6 yr) were treated with allogeneic BMT (11 as initial therapy, eight after ATG). Incidence of acute and chronic graft versus host disease was high, occurring in 14/16 and 4/11 patients at risk, respectively. Survival of BMT patients (18/19 transfused) was 32% at 7 yr. Of 63 patients treated with ATG, survival was 63% at 7 yr but decreased to 43% at 11 yr. The 2.5 yr survival following ATG was influenced by pretreatment disease severity (defined by percentage reticulocytes, granulocyte and platelet counts), age and--in patients under 45 yr of age--by sex. However, pretreatment disease severity was less in patients aged between 20 and 45 yr and in females. Concomitant androgen therapy, animal source of ATG, interval diagnosis--ATG (which was in general rather short) and aetiology did not influence survival. Thirty-four patients became transfusion independent for up to 26 months after ATG. A gradual increase in granulocyte and platelet counts could be observed over a period of many years, and 26 patients recovered to show a normal haemoglobin level, granulocytes greater than or equal to 1.0 X 10(9)/l and platelets greater than or equal to 100 X 10(9)/l). Late complications (paroxysmal nocturnal haemoglobinuria, myelodysplastic syndrome/acute leukaemia, hepatocellular carcinoma) were observed in nine patients who survived with autologous marrow function. Five died within 12 yr of initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250752 TI - Towards individually tailored empiric antibiotic therapy in febrile granulocytopenic patients. AB - The objective of this retrospective analysis was to study the possibility of a treatment strategy for febrile, granulocytopenic patients based on relative infective risks. Data from 441 adult febrile, granulocytopenic patients treated initially with antibacterial monotherapy were reassessed in terms of infection risk and outcome. Two different risk-groups were identified, namely those without and those with a clinical focus of infection (e.g. the respiratory tract and skin and soft tissue). Patients with a focus took longer to respond (4-8 days to defervesce) than those with unexplained fever, urinary tract infection or bacteraemia (2-3 days to defervesce). Patients with respiratory tract and skin and soft tissue infections received additional antibiotics more frequently (greater than 15% versus less than 10%) and were treated for a longer period (50% greater than or equal to 9 versus less than or equal to 8 days). More often the bone marrow had recovered at the time of response (48% versus 65%). These data suggest that a differentiated approach in the selection of initial antibiotics may be feasible, based upon continuous assessment of the patient's clinical condition. Antibiotic therapy may be postponed in patients without a focus of infection who show slowly increasing temperature. Patients with upper respiratory tract and skin and soft tissue infections may benefit from initial addition of penicillin and a glycopeptide, respectively. In cases of lower respiratory infections, antifungal therapy should be considered at an early stage. PMID- 2250753 TI - Hypopituitarism following complicated child birth (Sheehan's syndrome). AB - We describe two patients with hypopituitarism and a history of severe bleeding or hypotensive shock at the time of child birth. Both patients had a decrease of all or some endocrine functions of the anterior pituitary. Although the frequency of Sheehan's syndrome is low in developed countries, it should still be considered in the differential diagnosis of hypopituitarism. An interval of many years between delivery and time of diagnosis does not exclude the diagnosis. PMID- 2250754 TI - Electrocardiographic changes in acute malaria. AB - In this report of two patients with acute malaria, the electrocardiogram on admission showed changes of repolarisation. In both cases these electrocardiographic changes normalised after anti-parasitic treatment. The first patient recovered completely; however, the second patient developed signs of congestive heart failure compatible with cardiomyopathy. In acute malaria, an electrocardiogram should be considered to detect myocardial involvement. PMID- 2250755 TI - Non-Hodgkin's lymphoma and 1,25(OH)2D-related hypercalcaemia. AB - A patient with non-Hodgkin's lymphoma associated hypercalcaemia and a raised serum concentration of 1,25(OH)2D is described. Interestingly, both abnormalities were corrected with treatment. Data implicating calcitriol as an important immunoregulatory hormone are discussed. PMID- 2250756 TI - Acute nitrous oxide intoxication: clinical symptoms, pathophysiology and treatment. AB - Nitrogen dioxide is a representative of the group of compounds which may cause pulmonary symptoms after a symptom free interval. Even when there are no symptoms immediately following exposure to nitrogen dioxide, clinical observation is advisable, because severe pulmonary involvement can be the result. The present paper discusses the clinical symptoms which are observed in man after acute exposure to nitrogen dioxide, as well as the pathophysiological mechanisms involved. Practical therapeutic guidelines are given for dealing with the diagnostic difficulties concerning this type of intoxication. PMID- 2250757 TI - Is there a place for low molecular weight heparins? PMID- 2250758 TI - Selection of asymptomatic HIV carriers for antiviral therapy. AB - In order to find suitable markers for selection and monitoring of antiviral therapy in asymptomatic HIV-infected patients, we evaluated 18 anti-HIV positive individuals at three monthly intervals by HIV culture, HIV antigen, and core (p24) antibody testing as well as by measurement of lymphocyte subsets. Consistent results were obtained with HIV antigen, p24 antibody testing and T4 cell enumeration, whereas results of virus detection were variable. Therefore cumbersome and expensive virus culture is not of use in selecting patients for antiviral therapy. On the basis of our results and recent literature we currently propose using absence of p24 antibodies, presence of HIV antigen and low or falling T4 cells as eligibility criteria for antiviral therapy in asymptomatic infected individuals. PMID- 2250759 TI - Hereditary alpha-1-antitrypsin deficiency in duodenal ulcer. AB - An alpha-1-antitrypsin study was carried out on 184 patients with endoscopically proven duodenal ulcer, 66 first degree relatives of the patients and in 150 healthy controls, to establish the role of genetic factors in the etiology of duodenal ulcer. Alpha-1-antitrypsin served as a genetic marker in this study; it was estimated in terms of serum trypsin inhibitor capacity by the method of Jaccobson. Deficiency of alpha-1-antitrypsin level was recorded in patients as well as their family members when compared with controls. PMID- 2250760 TI - Acute HIV-infection: report of a case and a review of recent developments. AB - A patient is reported with a typical acute HIV-infection. He presented with an infectious mononucleosis-like illness, which included fever, malaise, sore throat, myalgia, swollen glands and a rash. Seroconversion, documented by serial immunoblotting, occurred within a period of four days. If a patient with a glandular fever-like illness belongs to one of the risk groups, an acute HIV infection should be seriously considered. In a recent study an association was found between the clinical course of acute HIV-infection and the subsequent course. Treatment of asymptomatic HIV-infected patients is discouraged, except if included in a clinical trial. PMID- 2250761 TI - Neutropenic enterocolitis in a patient with ovarian cancer after treatment with high-dose carboplatin and granulocyte macrophage-colony stimulating factor (GM CSF). AB - A 50-yr-old women is described with relapsed ovarian cancer. She developed neutropenic enterocolitis after treatment with high-dose carboplatin (1000 mg/m2) and granulocyte macrophage-colony stimulating factor (GM-CSF). The clinical features and the pathogenesis of neutropenic enterocolitis are discussed. This case is the first report of neutropenic enterocolitis associated with the treatment of carboplatin. PMID- 2250762 TI - Antihypertensive drug therapy: achievements, failures and prospects. PMID- 2250763 TI - Identification of two types of neurophysins in Xenopus laevis neurointermediate pituitary homologous to mammalian MSEL- and VLDV-neurophysins. AB - Xenopus laevis neurophysins have been purified from neurointermediate pituitaries through high-pressure reverse-phase liquid chromatography and their N-terminal amino acid sequences have been determined by microsequencing. Two types of neurophysins, corresponding to mammalian MSEL- and VLDV-neurophysins, have been distinguished. A strong homology exists between neurophysins of Xenopus (Pipidae), frog (Ranidae) and toad (Bufonidae). Xenopus MSEL-neurophysin, as frog MSEL-neurophysin, has a high molecular mass suggesting that the C-terminal domain of the vasotocin precursor is not processed in contrast to the two-step processing observed for mammalian vasopressin precursor. ABBREVIATIONS: Mammalian neurophysins are termed MSEL- and VLDV-neurophysins according to the nature of residues in positions 2, 3, 6 and 7 (one-letter symbols for amino acids). PMID- 2250764 TI - Effect of endothelin-1, endothelin-3 and C-terminal hexapeptide, endothelin (16 21) on motor activity in rats. AB - Intracerebroventricular administration of ET-1 (12.5 and 25 pmol/rat) and ET-3 (25 and 50 pmol/rat) induced the loss of the righting reflex and barrel-rolling behaviour in rats. The C-terminal hexapeptide ET(16-21) did not produce these effects. The automated recording of motor activity revealed that, unlike ET (16 21), both ET-1 and ET-3 evoke a dose-regulated increase of the immobility time. Pretreatment with peptidase inhibitors did not modify the activity of subthreshold doses of peptides. Since ET (16-21) display full agonist properties at ETB but does not interact with ETA receptors, the present data suggest that the behavioural syndrome induced by centrally administered ET-1 and ET-3 may be mediated by stimulation of ETA receptors. PMID- 2250765 TI - In vitro release of hypothalamic beta-endorphin (beta E) by arginine vasopressin, corticotropin-releasing hormone and 5-hydroxytryptamine: evidence for release of opioid active and inactive beta E forms. AB - The aims of the present experiments were: 1) to test whether substances which modulate beta-endorphin-immunoreactive (beta E-ir) release from the pituitary gland might act similarly in hypothalamic tissue; and 2) to further characterize the beta E-ir forms which are released from hypothalamus. To address these questions, hypothalamic tissue was incubated in vitro for 10 min periods in either normal media (basal conditions) or in media containing 55 mM KCl or one of several other test substances (stimulation conditions) and release was estimated by measuring the beta E-ir concentrations in the media. Depolarizing concentrations of K+ increased beta E-ir release 2-3 fold over basal levels and this effect appeared to be Ca2(+)-dependent. Dose-dependent increases in beta E ir release were elicited by nanonolar to micromolar concentrations of either corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), or 5 hydroxytryptamine (5-HT). Conversely, dopamine (1 microM) inhibited both the basal and K(+)-stimulated release of beta E-ir from hypothalamus. Gel filtration chromatography revealed that beta E1-31 and beta E1-27/beta E1-26 were the primary beta E-ir peptides released under either basal or CRH-stimulated conditions; the relative amounts of the beta E-ir peptides found in the media were nearly identical to those found in the hypothalamus itself. This result indicates that the release of different beta E-ir peptides into the media appears to be proportional to the relative amounts stored in tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250766 TI - Hypoprolactinemic effect of calcitonin gene-related peptide in the rat. AB - The effect of calcitonin gene-related peptide (CGRP) on prolactin (PRL) secretion was studied in female rats. Prepubertal female rats were submitted to the stressful stimuli of injection, blood puncture and thermal stress. Lactating rats were exposed to suckling stimulus. The effects of CGRP on PRL release were compared to those of calcitonin (CT). CGRP i.p. or s.c. prevents the increase in circulating PRL induced by stress. This effect was observed two hrs and even 24 hrs after CGRP administration. It was elicited at all doses tested, 2.5, 1.25 and 0.6 micrograms per animal. The time course of the actions of CGRP and CT are different. It is proposed that CGRP and CT act on different receptors. PMID- 2250767 TI - Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. AB - External jugular vein blood was sampled in the anesthetized cat during electrical stimulation of the superior sagittal sinus (SSS), and the levels of calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and neuropeptide Y (NPY) were measured with sensitive radioimmunoassays. CGRP levels rose by 85% and VIP levels by 300% while there was no change in SP or NPY levels in the same samples. These data provide the first evidence that activation of the trigeminovascular system, by selective stimulation of nociceptive craniovascular afferents, causes releases of vasodilator peptides and further implicates this system in the pathophysiology of migraine. PMID- 2250768 TI - Intrathecal administration of thiorphan and bestatin enhances the antinociception and release of Met-enkephalin induced by beta-endorphin intraventricularly in anesthetized rats. AB - Effects of bestatin and thiorphan administered intrathecally, on inhibition of the tail-flick response and the release of Met-enkephalin induced by beta endorphin administered intraventricularly were studied in anesthetized rats. Intrathecal pretreatment with 100 micrograms of thiorphan or bestatin potentiated the inhibition of the tail-flick response induced by beta-endorphin injected intraventricularly in pentobarbital anesthetized rats; the ED50 values for beta endorphin were decreased 5- and 7-fold by thiorphan and bestatin, respectively. To determine if the potentiating effect was due to the inhibition of the degradation of Met-enkephalin released by intraventricular beta-endorphin, the effects of intrathecal perfusion with thiorphan or bestatin on the release of immunoreactive Met-enkephalin from the spinal cord by intraventricular injection of beta-endorphin were studied. beta-Endorphin injected into the 4th ventricle at a dose of 5 micrograms increased immunoreactive Met-enkephalin in the spinal perfusate in urethane-anesthetized rats. Thiorphan or bestatin (1 x 10(-7) to 1 x 10(-4) M each) increased the amount of immunoreactive Met-enkephalin released by intraventricular beta-endorphin in a dose-dependent manner. The results provide additional evidence for the hypothesis that antinociception induced by beta endorphin is mediated by release of Met-enkephalin. PMID- 2250769 TI - [Indications for revascularization procedures in patients with intermittent claudication]. AB - Patients suffering from arteriosclerotic obliterating disease of the lower limbs that present with symptoms of rest pain, ulcers or more or less severe gangrene are considered as candidates for revascularization operation. Apart from the possible non relevance of individual symptoms, in some instances the revascularization operation is indicated solely on the basis of the angiographic evidence. Ascending thrombosis of the abdominal aorta, double or triple blocks, stenosis of the collateral circulation and, broadly speaking, any other situation that suggests a possible superimposition of an episode of acute ischaemia due to thrombosis in a condition of chronic obliterating arteriopathy are considered as absolute indication for revascularization operation. Patients whose conditions are not listed above are considered as stage II and indication for operation in this case is not absolute but relative or "luxury" since its purpose is only to improve the quality of life. The importance of the symptoms must be considered along with other factors, including the personal, social, working, sporting and psychological needs of the specific individual apart from the absence of general risks related to the patient's condition. The vascular surgeon's expertise is obviously fundamental in exactly evaluating the arteriography and in understanding the precise anatomic picture that varies in every single case: in fact, since the operation is optional and not a necessity, correction of the arterial lesions in only advisable when it is possible to carry out and operation that is broadly risk free and with good short and long term results, with reference to the patient's life expectancy. PMID- 2250770 TI - [Improved survival in the treatment of ruptured abdominal aortic aneurysm]. AB - Personal experience in the management of 70 ruptured abdominal aortic aneurysm over the past 5 years is reported dividing patients into 2 groups, before and after establishment of intensive care unit: survival was 30.76% on the first, 66.66% in the second. Factors that allowed that result are discussed. PMID- 2250771 TI - [Systemic effects of intravenous dipyridamole in patients of various age groups]. AB - Aim of this study was to assess the role of age-related vascular response in the onset of i.v. dipyridamole effects. The results of 129 patients who underwent a dipyridamole infusion were reviewed. The patients were divided into three according to age: 47 patients of less than 50 years (group I), 54 patients aged between 50 and 60 years (group II) and 28 patients of more than 60 years (group III). For each group heart frequency (HF) and systolic blood pressure (SBP) were considered in basal conditions, at the end of infusion and at the minimum value of SBP (SBP min); moreover the time in reaching SBP min was considered (time to SBP min). At the end of the infusion no significant changes in SBP were observed in all groups while the SBP min value reached from group III were significantly lower than basal (142.6 +/- 20.4 mmHg, p less than 0.02). The HF, without significant differences among the three groups in basal conditions, increased significantly at the end of infusion only in group I and II, with a more significant increase in group I at the time of SBP min with respect to groups II and III. The group 3 showed moreover, a significant longer time to SBP min (286 +/- 208 sec) respect to the group I and II (145 +/- 130 and 160 +/- 177 sec respectively) (p less than 0.02). From these data it can resume that age could be a factor to determine hemodynamic response to intravenous dipyridamole. PMID- 2250772 TI - [Effects of i.v. nicardipine in the treatment of hypertensive crisis]. AB - The availability of i.v. nicardipine has urged us to prove this drug in the treatment of hypertensive attacks (SAP greater than or equal to 210 mmHg and/or DAP greater than or equal to 110 mmHg). Two groups of patients (each made up of ten subjects) were treated with 2 mg and 5 mg respectively of i.v. nicardipine injected for 4 min while mean systolic and diastolic arterial pressure and heart rate were registered until three hours. I.V. nicardipine administration induced in both groups of patients a decrease in systolic pressure from 20 to 30% while diastolic arterial pressure decreased from 15 to 18% in the first group and from 20 to 25% in the second one. Heart rate showed an initial mild increase following arterial vasodilator action of nicardipine whereas it decreased significantly from 120 min in the presence of an unchanged hypotensive effect of the drug. One patient did not respond to nicardipine while another felt chest pain and palpitations. In conclusion our results are satisfactory and argue for the inclusion of nicardipine among the drugs that may be considered useful for the treatment of hypertensive attacks. PMID- 2250774 TI - [Surgical treatment of 100 patients with perforated pyloric ulcer. Immediate and follow-up results]. AB - The aim of this study was to assess the results of different surgical treatments in 100 patients admitted from 1972 to 1984 with perforated pyloric ulcer. Forty six patients were treated with simple suture, thirty-two patients underwent high selective vagotomy with pyloroplasty, 13 patients were submitted to truncal vagotomy with pyloroplasty and 9 to gastrectomy. This study has shown that high selective vagotomy and pyloroplasty for perforated pyloric ulcer can be performed as safely as simple closure. The overall clinical results according to the Visick classification were recorded as excellent or very good in 85 per cent of patients treated with high selective vagotomy with pyloroplasty versus 38 per cent with similar results in simple closure patients. We conclude that high selective vagotomy with pyloroplasty is not less effective for treatment of pyloric perforated ulcer than for duodenal ulcer; simple closure should be reserved for patients treated long time after perforation and with advanced age or in patients with serious associated pathology. PMID- 2250775 TI - [Latero-lateral choledochoduodenostomy in benign pathology of the common bile duct. A prospective study]. AB - Biliodigestive derivations for benign diseases of the biliary tract are currently accepted in case of extended to recurrent choledochal stenosis, excessive dilation of the choledochus, impacted ampullary stones. This paper concerns 19 subjects that underwent laterolateral choledochoduodenostomy (CDS) according to the Roesner technique over the period January 1986 through December 1987 in order to evaluate long-term functional results of this operation. Hepatic serum enzymes and bilirubin were determined at intervals of two weeks during the first three months and of four weeks until the sixth month postoperatively. At this time a battery of controls was performed, namely standard plain X-ray of the abdomen, hepatobiliary sequential scintigraphy with HIDA, endoscopic examination of the anastomosis. The level of serum enzymes was then determined at 18 months postoperatively and scintigraphy was repeated as well. Based on the results of this study and the review of the recent literature, our opinion is that CDS has shown as a safe procedure with good long-term results in the treatment of benign disease of the biliary tract, mostly if high-risk aged subjects are concerned. PMID- 2250776 TI - [Technical note: total duodenal diversion using GIA]. PMID- 2250773 TI - [Evaluation of the efficacy and tolerability of sustained-release nifedipine in arterial hypertension. Continuous monitoring of arterial pressure]. AB - The anti-hypertensive efficacy of slow-release nifedipine 20 mg twice a day was investigated in 20 consecutive patients (13 females and 7 males, mean age 50.3 +/ 9.9 years) with mild to moderate hypertension (mean casual BP 162.2 +/- 7.5/103.1 +/- 4.7 mmHg) continuous blood pressure monitoring and routine laboratory tests were performed before and after three months of continuous therapy, whereas casual blood pressure was assessed after one and three months of therapy. RESULTS: In 4 patients, all female, adverse effects (headache) led to discontinuation of therapy. In the other 16 patients casual blood pressure decreased to 149.8 +/- 12.7/95.3 +/- 6.6 after one month and to 148.7 +/- 11.7/91.4 +/- 7.1 after three months (p less than 0.05 and became normal after three months in 11 patients (68%). Continuous blood pressure monitoring showed a significant fall in systolic and diastolic day time blood pressure (from 132.8 +/ 6.0/87.9 +/- 5.1 - p less than 0.02) and in systolic night time blood pressure (from 117.1 +/- 6.6 to 107.1 +/- 5.1 - p less than 0.02) without changing the shape of the circadian profiles. No significant changes in systolic blood pressure variability were observed. There was no correlation between pretreatment blood pressure levels and the extent of blood pressure fall during therapy. Heart rate, body weight and all biochemical parameters remains unchanged. CONCLUSION: Our findings confirm the antihypertensive efficacy of slow release nifedipine. This study does not concord with other reports regarding the tolerability of this drug in women. However the small number of patients does not allow any firm conclusions to be drawn. PMID- 2250777 TI - [A variant of Bassini's method in radical surgical treatment of direct inguinal hernia]. AB - The paper reports a technical device used in Bassini's original operation for radical surgery of inguinal hernias. On the basis of results achieved in the treatment of 238 cases, it is thought that this easily and quickly performed device may be taken into consideration particularly in the treatment of direct inguinal hernias. PMID- 2250778 TI - [Use of pulsed expansion in lengthening of tubed cutaneous flaps. Experimental study]. AB - The Authors describe an intermittent pulsed pressure methodic applied to bipedicle tubed flaps prepared on the back of the rabbit. Clinical, thermographic, and histological data have demonstrated the safety of the flaps and a microvascular bed increase larger than in inexpanded ones. PMID- 2250779 TI - [Carcinoma of the Vater's ampulla: local exeresis or major resection?]. AB - Ampullary carcinoma are uncommon and case reports are fragmentary and small in number. The varied histotypes, tumour grading and staging methods, together with the different risk factors involved and diverse operating procedures make comparison difficult. The paper makes a contribution towards the number of cases reported and discusses the problems arising from this pathology. PMID- 2250780 TI - [Anorectal lesions in Crohn's disease. Our experience]. AB - Nine years experience of anorectal surgery for Crohn-related lesion have been analysed. The series regards only 14 cases with pathology including ragade, abscesses and anocutaneous and retrovaginal fistulas. Treatment was as conservative as possible except for cases in which fistulizations led to sepsis as a result of which some adjustments had to be made and proctectomies in incontinence. PMID- 2250781 TI - [Endoscopic polypectomy of the stomach]. AB - Until 1970 endoscopy of the digestive tract was the only diagnostic method available. After this date, the introduction of endoscopic polypectomy enabled patients affected by these lesions to be treated, and at the same time considerably reduced their length of stay in hospital. The paper reports the results of 346 gastric polypectomies performed in 187 patients from 1974 to the present. PMID- 2250782 TI - [Role of colonoscopy in the diagnosis of ischemic colitis as a complication of surgery of aneurysms of the abdominal aorta]. AB - Ischaemic colitis is one of the complications following aortic reconstruction for abdominal aortic aneurysm. The diagnosis and monitoring of this complication can be helped by a left colonoscopy. Through an endoscopic valuation of 18 patients, the Authors value the incidence of colonic mucosal or mucosal and muscularis ischaemia following aortic aneurysmectomy with inferior mesenteric arterial ligation. PMID- 2250784 TI - [Use of a new anti-inflammatory drug in the treatment of varicophlebitis of the lower limbs]. AB - The paper reports the results obtained in 20 patients affected by varicophlebitis of the lower limbs following the oral administration of an anti-inflammatory substance. Results were compared with findings in single-blind study performed in a group of 20 patients treated with placebo. The evaluation of residual signs and symptoms and the control of recanalization of venous collectors using Doppler tests revealed a difference between the two groups in favour of the patients treated with the anti-inflammatory agent, although this was not statistically significant. The use of the drug was considered useful as a support to conservative varicophlebitis therapy with the aim of accelerating the resolution of the inflamed condition and thus reducing the functional disability of the limb. PMID- 2250785 TI - [Short-term antibiotic prophylaxis in cholecystectomy]. AB - After describing the stages of surgical infection and the efficacy of short-term antibiotic prophylaxis in surgery, the paper reports a trial in which a single dose of Ceftriaxone was administered in 50 cases of cholecystectomy, with excellent results in terms of efficacy and tolerability. PMID- 2250786 TI - [Amikacin in the topical treatment of small losses of substance]. AB - The paper describes the use of aminoglucoside amikacin over 3 years in a group of 187 patients for the topical treatment of skin lesions extending over a maximum 10% of body surface area. The use of amikacin for topical treatment was chosen on the basis of clinical factors; in the majority of cases these were associated to poor circulation in the affected region which created uncertainty as to whether an efficacious dose would be provided by intravenous administration. PMID- 2250783 TI - [Prevention of deep venous thrombosis after abdominal surgery]. PMID- 2250787 TI - [Mesenteric fibromatosis in Gardner's syndrome]. AB - The paper reports a case of mesenteric fibromatosis with familial polyposis, an association which was diagnosed as Gardner's syndrome, and highlights the complications connected to mesenterial desmoid tumours. In addition, the importance of radical surgical therapy of these neoplasias is underlined. Lastly, it is hypothesised that full screening of patients affected by familial polyposis might show a greater incidence of association between widespread polyposis and pathological changes attributable to Gardner's syndrome. PMID- 2250788 TI - [Volvulus of the gallbladder. Presentation of a case and review of the literature]. AB - A case of acute torsion of the gallbladder in a 83-year old woman is presented. According to the literature, the pathogenetic mechanism, the anatomical bases and the clinical presentation of this disease are discussed. The age intervals more often affected are the pediatric and teen-ager and, mostly, the elderly over the 70's. The basic anatomical defect is the gallbladder flotation, congenital or acquired. The clinical feature is that of right acute abdomen, and emergency cholecystectomy is the treatment of choice. PMID- 2250790 TI - [Intestinal obstruction caused by volvulus of Meckel's diverticulum. Description of a case]. AB - A case of intestinal occlusion is reported caused by volvulus of Meckel's diverticulum. The etiological and clinical aspects are discussed together with their implications in terms of suitable surgical therapy. PMID- 2250791 TI - On giving and getting. PMID- 2250789 TI - [Carcinoma of the parathyroid glands. Apropos of a case associated with thyroid struma]. AB - The paper reports a case of carcinoma of the parathyroid associated with thyroid struma and underlines the difficulties of intraoperative diagnosis and the surgical approach which should be adopted on the basis of this finding. Often the diagnosis of the malignant nature of the neoplasia is based on the possible appearance of local or distant recurrence rather than histological examination. PMID- 2250792 TI - Nit-picking details. PMID- 2250793 TI - Response to Alexander and Marks. PMID- 2250794 TI - The fate of nursing education funding. PMID- 2250795 TI - An interview with Carolyne K. Davis. Interview by Barbara J. Barnum. PMID- 2250796 TI - Resource utilization in home care. Methods and issues. PMID- 2250797 TI - Predicting licensed nurse turnover in skilled long-term care--organizational characteristics, climate, and group characteristics. AB - Chambers gives us information on turnover that directors of skilled long-term care facilities will want to know. The study looks at organizational characteristics, employee group characteristics, and work climate, as they relate to nurse turnover. PMID- 2250798 TI - Toward description. Public health nursing and community health nursing are different. PMID- 2250799 TI - Wear your designer clothes on duty. The Diane Von Furstenberg collection. PMID- 2250800 TI - Marine natural products. PMID- 2250801 TI - Applications of interactive computer graphics in analyses of biomolecular structures. PMID- 2250802 TI - Monoterpenoids. PMID- 2250803 TI - Writing in the disciplines: a nursing faculty perspective. AB - The author discusses how nurse educators can enhance students' writing abilities, concluding with strategies to promote good writing in nursing programs. The author shares her experiences with a university-wide writing in the disciplines and a writing ombudsmen program. PMID- 2250804 TI - Success in nursing: a primary intervention course. PMID- 2250805 TI - Learning from management videos: the producers' point of view. AB - Desiring to use videotapes to teach nursing management and failing to find commercially available tapes on needed topics, the authors produced their own tapes on using a decision tree, negotiating a labor contract, leading a quality circle discussion, defending a budget request, conducting an evaluation conference, and leading a brainstorming session. Having identified the underlying principles for each topic, they wrote scripts for 15 minute vignettes dramatizing a nurse manager's use of each technique. They directed nursing and theater students' portrayals of the characters for each vignette. The edited videotapes of managerial interventions proved to be effective models for nurses enrolled in basic management courses. The scriptwriter, director, camera operator, and student actors all acquired an in-depth understanding of the videotaped managerial interventions through their research and prerehearsal conferences. PMID- 2250806 TI - Education-service interaction group. PMID- 2250807 TI - Routes to acceptance: implementing a wellness focused curriculum. AB - How do faculty and students react to the integration of the concept of wellness into curricula? At first, the two groups respond very differently. In time, they accept the concept of wellness and use it in their nursing practice. The implementation of wellness in one community college program has strengthened the belief that nursing has an independent function in health care. PMID- 2250808 TI - The art of nursing. AB - The author presents a framework for artistic nursing practice that fits within the nursing process and balances scientific principles with artistic concepts. The framework can be used by nurse educators to help them teach the qualitative aspects of nursing care. In addition, artistic concepts which relate to the nursing process, including vision, composition, theme, perspective, congruency, line, color, tone, style, technique, and intensity are discussed. PMID- 2250809 TI - Critical thinking and computer-assisted instruction. PMID- 2250810 TI - Avoiding student-faculty litigation. AB - Nursing faculty have a duty to meet a standard of care to the patient and a standard of conduct to the student. Their double responsibility puts them at increased risk for potential lawsuits. The author presents an overview of the American legal system and discusses three areas of the law and its effect on the student-faculty relationship. PMID- 2250811 TI - On being mentored: a personal experience. PMID- 2250813 TI - Dual assignments: an effective clinical teaching strategy. PMID- 2250812 TI - Enrichment for academic success: helping at-risk students. AB - Successful retention of at-risk nursing students is best accomplished through an organized system that addresses their individual needs in the areas of academic, cognitive, and self-enhancement skills. The cooperative endeavors of students, faculty, and administrators in the development of one such system, Enrichment for Academic Success, has resulted in a 95% retention rate among participants. The authors describe the incentive, development, implementation, and value of the system which can be adapted to any setting with adequate human and material resources. PMID- 2250814 TI - Program evaluation. Part 2: A responsive model proposal. AB - While program evaluation is necessary for understanding and improving educational programs in nursing, it is frequently surrounded by a climate of unease and perplexity. The first article (September/October 1990) in this two-part series reviewed models of program evaluation. This second article examines the state-of the-art of program evaluation in nursing education and proposes implementation of a responsive model of evaluation in schools of nursing. The series aims to foster more dynamic, efficient program analysis, thereby enhancing the effectiveness of nursing education programs. PMID- 2250815 TI - Mental handicap. The value of outdoor activities. PMID- 2250816 TI - Introducing quality assurance. PMID- 2250818 TI - District experience on Project 2000. PMID- 2250817 TI - A course designed to fit. PMID- 2250819 TI - Nursing abroad. An African adventure. PMID- 2250820 TI - In praise of primary nursing. PMID- 2250821 TI - A tale of two cities. PMID- 2250822 TI - Too busy for assessments? PMID- 2250824 TI - Discrimination may be the result of routine testing. PMID- 2250823 TI - The missing link. PMID- 2250825 TI - Changing the culture. PMID- 2250827 TI - Young women at risk of fracture. PMID- 2250826 TI - HIV update. PMID- 2250828 TI - Agency nurse blues. PMID- 2250829 TI - Marketing nurses' skills. PMID- 2250830 TI - Nursing: a basic or an applied science? PMID- 2250831 TI - Research professionalism. PMID- 2250832 TI - Nursing practice: guided by or generating theory? PMID- 2250833 TI - Caring in nursing: analysis of extant theory. AB - Caring in nursing as a substantive area of nursing science has been the focus of considerable scholarly effort. Based on the assumption that caring is the central concept in nursing and is uniquely known and expressed in nursing, this paper focuses on an analysis of major theoretical works related to the concept. Five categories of questions provide a framework for the analysis: ontological, anthropological, ontical, epistemological, and pedagogical. PMID- 2250834 TI - Consumer-centric advocacy: its connection to nursing frameworks. AB - The concept of advocacy is redefined here as consumer-centric advocacy and its essential attributes are identified. Theoretical linkages between advocacy and selected nursing models are described. Specifically, the construct of advocacy is considered as it is operationalized within the theoretical frameworks of King, Newman, Orem, and Rogers. The health care system in the United States is in a state of unrest and undergoing nearly continuous change and reorganization. This reorganization has been hastened by tightened resources within the health care financing system, a growing number of elderly and indigent needing care, and the advent of care intensive disease processes such as AIDS and substance addicted newborns. In addition, the general public has become better informed concerning health and is seeking new approaches to the delivery of health care services. As changes in the health care system continue to occur, the role of nurses, the largest group of health care providers also is changing. In a system in which there is both a shortage of registered nurses and a growing demand for their services, nurses must develop strategies to maximize their impact on the health care system to meet the needs of consumers as well as protect their own professional integrity. The development of such strategies within nursing frameworks may be facilitated by closer scrutiny and clarification of the nurse's traditional role as advocate. PMID- 2250835 TI - The lived experience of self-transcendence in women with advanced breast cancer. AB - The purpose of this exploratory study was to describe the lived-experience of self-transcendence in women with Stage IV breast cancer. A phenomenological approach was chosen for the research design and analysis. Five women who had lived with metastatic disease from 2 to 7 years described experiences from which they derived an increased sense of self-worth, purpose in life, and interconnectedness with others. The self-transcendent experiences involved an effort on the part of the participants to reach out beyond themselves to help other women, to permit others to help them, or to "just accept" unchangeable situations. The results indicated that participants found meaning in their lives in the face of life-threatening illness. Although nurses can not be expected to create self-transcendent experiences for their patients, they may be able to establish and maintain conditions in which the phenomenon occurs. PMID- 2250836 TI - Struggling in change: from the traditional approach to Parse's theory-based practice. AB - This paper presents the struggle of a nurse who changes in practice from being guided by the traditional problem-based approach to being guided by Parse's theory of nursing. Experiences that led to the change are described, and specific practice situations from an acute care setting demonstrate how values and beliefs about human beings and health transformed over time. The nurse's changed values and beliefs lead to a different approach in practice. The nature of the nurse person relationship is described as it relates to Parse's practice dimensions and processes: illuminating meaning through explicating what is, synchronizing rhythms through dwelling with, and mobilizing transcendence through moving beyond. Emerging patterns of health are presented as an alternative to problem based statements for guiding nurse-person activities. The value of Parse's theory for guiding practice is offered as it relates to the individual's perspective of enhanced quality of life and the nurse's perspective of professional practice. PMID- 2250837 TI - The struggle of the diagnosed terminally ill person to maintain hope. AB - Clinical, empirical, and subjective data are used to explore the concept of hope as it is lived by persons who are diagnosed as terminally ill. Interviews with 11 men who were in stage 2 (asymptomatic) HIV disease explicate the form that hope takes and its role in promoting health when a person must cope with a serious diagnosis. Other research and ideas about hope and dying are presented and a critique is presented of both these ideas and current nursing practice. PMID- 2250838 TI - HIV in the dental office: a review of the evidence. PMID- 2250839 TI - Oral cancer on the rise for women. PMID- 2250840 TI - Digging up clues from the past. Dental exam of the Chumash Indians. PMID- 2250841 TI - Dental advertising. A patient attitude survey. PMID- 2250842 TI - Temporomandibular symptoms and occlusion: a review of the literature & the concept. AB - The role of occlusal factors in the etiology of temporomandibular disorders (TMD) is reviewed. The rediscovery of TMD by J.B. Costen in 1934 and the origin of this concept are historically linked. Difficulties in scientifically studying TMD are addressed. TMD lacks specific indicators (signs and symptoms), are episodic and respond to placebos. Clinical success with specific literature (experimental, epidemiological and clinical studies) reviewed fails to support the concept that occlusal factors play a significant role in the etiology of TMD. The remodeling capacity of the temporomandibular joint demonstrates that the joint can accommodate and adapt to various occlusal conditions. PMID- 2250843 TI - A portrait of Poppa. PMID- 2250844 TI - Smoking control policies. PMID- 2250845 TI - Stress in life and work. Part 2: Stress in the workplace. PMID- 2250846 TI - Why you need safe and healthy flooring. PMID- 2250847 TI - 'Passive smoking is an industrial injury'. PMID- 2250848 TI - What is "the best care?". PMID- 2250849 TI - Matched group study of surgical resection versus cobalt-60 plaque radiotherapy for primary choroidal or ciliary body melanoma. AB - We report the results of a nonrandomized, matched-group, survival and visual preservation study of patients with a choroidal or ciliary body melanoma managed by microsurgical resection of the tumor versus cobalt-60 episcleral plaque radiotherapy. Each treatment group consisted of 30 patients. All patients were matched on a case-by-case basis in terms of tumor size (largest linear tumor dimension), location of the anterior tumor margin relative to the ora serrata, location of the posterior tumor margin relative to the equator, and age at the time of treatment. Although the estimated actuarial 5-year survival probability was slightly greater in the resection group (85.2%) than in the cobalt plaque group (81.8%), this difference was neither clinically impressive nor statistically significant. In contrast, there was a substantially higher rate of early posttreatment severe visual loss in the resection group (P = .0008, Mantel Haenszel test). PMID- 2250850 TI - Current trends in suture fixation of posterior chamber intraocular lenses. AB - Corneal surgeons were surveyed with regard to their technique of suture fixation of posterior chamber intraocular lenses in the absence of posterior capsular support. Fifty-nine percent of the 260 respondents stated they perform the procedure almost exclusively during penetrating keratoplasty. Scleral fixation was marginally favored over iris fixation by these surgeons. Most intraoperative problems reported were related to the relative technical difficulty of the procedure, although transient hemorrhage from the ciliary body was also mentioned. Postoperative complications cited included mechanical problems involving the lens and iris, cystoid macular edema, glaucoma, and endophthalmitis. PMID- 2250851 TI - Ocular anesthesia for cataract surgery: a direct sub-Tenon's approach. AB - We describe a new technique in which ocular anesthesia is obtained by dissection of the superior quadrants, as in strabismus or retinal surgery, followed by direct infusion of the retrobulbar space with local anesthetic agent, using a blunt 19-gauge cannula. In 112 cases of cataract surgery in which we used this direct sub-Tenon's approach, we found it to be a safe, simple, and effective method of achieving rapid ocular anesthesia. PMID- 2250852 TI - Trabecular pigmentation following extracapsular cataract extraction and posterior chamber intraocular lens implantation. AB - We prospectively evaluated the change in trabecular pigmentation following extracapsular cataract extraction and posterior-chamber intraocular lens implantation in 70 patients (94 eyes) with senile cataracts. Using the Boys-Smith pigment gradation lens to measure semiquantitatively the amount of pigment visible in the angle, we estimated the mean trabecular pigmentation preoperatively and at 3-month intervals postoperatively. Both the mean pigmentation and the number of eyes with heavy pigmentation rose after the operation and then gradually returned to preoperative levels. There was no correlation between the amount of trabecular pigmentation and intraocular pressure. PMID- 2250853 TI - Glaucoma secondary to epithelial downgrowth and 5-fluorouracil. AB - Since epithelial downgrowth involves an actively proliferating intraocular tissue, it is possible that the antimetabolite 5-fluorouracil may inhibit it. We report a case of secondary glaucoma caused by epithelial downgrowth in which filtration surgery was performed with adjunctive use of subconjunctival 5 fluorouracil. On cessation of the injections, the retrocorneal membrane grew rapidly to involve the entire posterior cornea. The eye eventually became blind and painful and was enucleated. The use of 5-fluorouracil given in the usual manner appears to have been a failure. PMID- 2250854 TI - Use of a symblepharon ring for treatment of over-filtration and leaking blebs after glaucoma filtration surgery. AB - We report the use of a symblepharon ring in the treatment of seven cases of flat anterior chamber (six cases of total iridocorneal touch, and one of corneallens touch) secondary to overfiltration or to bleb leak. In all cases, the anterior chamber reformed within 24 hours after the symblepharon ring was used. Advantages of using the ring are: (a) it permits testing of visual acuity, tonometry, and intraocular examination without removing it; (b) it does not require suturing to the conjunctiva; (c) it does not disturb the corneal epithelium; (d) it may be available at institutions lacking other shells; and (e) it is cost-effective. PMID- 2250855 TI - Hemihang-back recession: description of the technique and review of the literature. AB - We describe a modification of the hang-back and loop techniques that we call the hemihang-back recession, in which the muscle is reattached to the sclera posterior to the original insertion with a single, absorbable suture. We recommend it for difficult strabismus cases, specifically when recessions of 7 mm or more are required. PMID- 2250856 TI - Scleral buckle revision to treat recurrent rhegmatogenous retinal detachment. AB - Recurrent rhegmatogenous retinal detachment sometimes occurs following scleral buckling surgery in the absence of advanced proliferative vitreoretinopathy (grade C-2 or greater). Such detachments can occur because: 1) the scleral buckle is not properly positioned beneath the original break; 2) the buckle is not high enough; 3) the break is elevated off the buckle due to progressive vitreous traction; 4) there are new breaks; and 5) chorioretinal adhesion is insufficient. Techniques that may be useful for reattaching the retina in these cases include: 1) adding scleral buckling material to augment the original buckle; 2) modifying the existing buckle without adding new material; 3) replacing the original buckle with other material; 4) re-treating inadequately closed breaks; and 5) combinations of these four techniques. Vitrectomy may be avoided in many cases. PMID- 2250857 TI - Posterior horizontal and vertical tightening to treat combined punctal ectropion with medial canthal tendon laxity. AB - The classical operations to treat either medial canthal tendon laxity or punctal aversion occurring alone possess drawbacks if they are used to treat these conditions when they occur simultaneously. A simplified procedure is described whereby tissue is removed via a posterior eyelid approach so that the eyelid may be tightened both horizontally and vertically, thus inverting the punctum and fixating it in the lacrimal lake. This procedure is quite easy to perform and can be done under local anesthesia in the office. PMID- 2250858 TI - Retinal toxicity and in vitro efficacy study of cilofungin (LY121019). AB - We assessed the retinal toxicity of a new antifungal agent, cilofungin, by injecting it into the vitreous body of albino rabbit eyes in dosages of 2.5 micrograms to 320 micrograms. The maximum intravitreal drug concentration (320 micrograms) produced no histological evidence of retinal toxicity. Electroretinography data showed some variations, but no toxicity at the highest dose (320 micrograms). When efficacy was evaluated in vitro against Candida albicans, the minimal inhibitory concentration was 2.50 micrograms/mL, using Sabouraud's broth or M3 medium. The minimal fungicidal concentration was 5 micrograms/mL with Sabouraud's broth, and 10 micrograms/mL with M3 medium. Cilofungin is a potentially safe antifungal for the treatment of candida endophthalmitis. PMID- 2250859 TI - Learning curve for radial keratotomy. AB - I prospectively evaluated my own learning curve for radial keratotomy (RK) by comparing the results achieved in two groups: 20 consecutive eyes on which I performed RK without having had previous experience with the procedure (group 1); and 20 other eyes, matched for age, sex, and preoperative refractive error, on which I performed RK after I had performed the procedure 250 times (group 2). Although there were nine microperforations in group 1 and none in group 2, the postoperative refractions and uncorrected visual acuities were similar in both groups. Since the microperforations had no adverse effect on the visual results, it is reasonable to conclude that there was, in effect, no learning curve involved in my experience with RK. PMID- 2250860 TI - Endophthalmitis after placement of a Molteno implant. AB - I report a case of early postoperative endophthalmitis following placement of a Molteno implant. Excellent results were obtained by immediate removal of the implant and surgical management of the infection, followed by replacement of the implant. PMID- 2250861 TI - Thermal side reactions. PMID- 2250862 TI - Congenital eyelid eversion. PMID- 2250863 TI - Preferred practice patterns. PMID- 2250864 TI - Sympathetic ophthalmia following Nd:YAG cyclotherapy. PMID- 2250865 TI - Role of communities in decision-making eye care programs. AB - The concept of primary health care involves educating people to live their lives in ways beneficial to their health. Communities as a whole must participate in the decision-making that is involved in such education, be it promotive, preventive, curative, or rehabilitative. I refer to this participation as "participatory communication." It is based on two fundamental tenets: 1) Everyone in a community has some special knowledge to contribute to the development of the health of that community; and 2) No person is superior to another. Subsequent to sociological and anthropological studies of communities in the Southern Sudan by the Norwegian Church Aid, the Norwegian Association of the Blind and Partially Sighted conducted village workshops based on this concept. PMID- 2250866 TI - Visual results and complications of transsclerally sutured intraocular lenses in penetrating keratoplasty. AB - We retrospectively reviewed the charts of 56 consecutive patients who had undergone penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens. Follow-up ranged from 3 to 28 months (mean, 11.1 months). Postoperative visual acuity improved in 46 patients (82%), remained the same in eight (14%), and worsened in two (3.6%). In 32 patients with at least 10 months' follow-up, best corrected visual acuity as measured with a pinhole or hard contact lens was 20/40 or better in 12 (38%), 20/50 to 20/10 in 10 (31%), and 20/200 or worse in 10 (31%). Problems with lens decentration, tilt, or scleral suture-related infections were minimal. Glaucoma was the msot common cause of decreased vision in patients with 10 or more months' follow-up. Three patients (5.4%) developed rhegmatogenous retinal detachments early in the postoperative course. PMID- 2250867 TI - Small-incision techniques in ophthalmic plastic surgery. AB - A stepped surgical incision, in which an initial small cutaneous incision is followed by progressively longer incisions in the subcutaneous tissues, limits postoperative scar formation in the skin. Placement of incisions parallel to relaxed skin-tension lines further reduces the size of the scar. We describe how these principles may be applied to ophthalmic plastic surgical procedures to improve cosmesis. Autogenous fascia lata can be harvested with scissors through a 15-mm incision parallel to relaxed skin-tension lines, placed over the middle of the iliotibial tract. Lacrimal bypass operations can be performed well and with good cosmesis through a 12 to 15-mm skin wound if the above principles are followed. PMID- 2250868 TI - Central retinal vein obstruction and axial length. AB - The axial lengths of 24 consecutive adult eyes with unilateral central retinal vein obstruction (CRVO) were compared with those of contralateral unaffected eyes and those of a control population. The lengths of the two eyes of persons with a unilateral CRVO were not significantly different. By contrast, eyes of persons with CRVO averaged 0.67 mm (approximately 2 diopters) shorter than their control counterparts (P = .03). This anatomic difference may be a factor in the development of CRVO. PMID- 2250869 TI - The chamber-retaining suture revisited. AB - In 1977, C. William Simcoe developed the anterior chamber-retaining suture as a means of preventing intraocular lens-cornea touch during intraocular lens manipulation, penetrating keratoplasty, and following filtration surgery. Though seldom remembered today, Simcoe's innovation safely and effectively insures corneal well-being following increasingly complex modern filtration and shunt procedures. The use of a combination of double-armed 9-0 nylon suture and anterior chamber-bridging straight needles simplifies placement. PMID- 2250870 TI - Ocular trauma caused by exploding glass bottles containing dry ice and water. AB - We treated three patients with severe ocular injuries caused by exploding glass bottles containing a mixture of dry ice chips and water. One patient had a corneal laceration and traumatic cataract with several retained intraocular glass fragments. The second had a scleral laceration without corneal or lenticular involvement. The third suffered a corneal-scleral laceration, with a total retinal detachment. Following surgery, two patients recovered 20/20 vision; the third patient regained only light perception. PMID- 2250871 TI - Techniques of adjustable suture strabismus surgery. AB - Adjustable sutures allow eye muscle positions to be changed following strabismus surgery, when the patient is awake and able to cooperate in muscle balance testing. Bow-tie-knot and sliding-handle sutures can be adjusted within 24 hours after surgery. Scleral traction sutures, which can be used to fix the globe to periorbital tissues during postoperative healing, can be adjusted for up to 14 days after surgery. We describe these techniques as well as an adjustable loop suture for conjunctival closure. PMID- 2250872 TI - Phacofragmentation of a hard lens nucleus in the posterior segment. AB - Foreign body forceps were used to stabilize a hard lens nucleus during phacofragmentation in the posterior segment. This technique allows removal of the hard lens nucleus with minimal manipulation and without the need for a larger incision. PMID- 2250873 TI - Severe anterior segment inflammation following corneal surgery for keratoconus. AB - We present three keratoconus patients who experienced severe anterior segment inflammation, two following penetrating keratoplasty, and one following epikeratoplasty. A favorable response to indomethacin therapy in the second eyes of these patients suggests that the inflammation in the first ones was prostaglandin mediated. PMID- 2250874 TI - Isolated venous macroaneurysm. PMID- 2250875 TI - A new anterior capsular opening: dumbbell opening--its efficacy in the human eye. AB - Using excised pig eyes and a human eye-bank eye, we demonstrated the efficacy of our new anterior capsular opening, the dumbbell opening, especially for the human eye. The opening consists of two microcircular holes made by an automated electric microtrephine, connected by a straight cut made with scissors. The 3.5 mm-long dumbbell opening fully retained its original shape after cataract removal and posterior-chamber intraocular lens insertion. PMID- 2250876 TI - Silicone vascular loop used in tarsorrhaphy. PMID- 2250877 TI - The irrigating knife: an ultrasharp surgical blade with irrigating system. AB - We present an irrigating microsurgical knife for ocular surgery. Irrigation of balanced salt solution through the knife tip during sectioning removes hemorrhages continuously, allowing uninterrupted sectioning, without cauterization of bleeding vessels. The "zero degree" knife can be bent in any required position. PMID- 2250878 TI - A new ophthalmic microtrephine. AB - We present a new instrument designed to facilitate the microtrephination of tissues required in various ophthalmic procedures. This microtrephine is a 21 gauge stainless steel tube, 0.81 mm in diameter and 16 mm long, with a sharpened cutting end and a plastic finger-grip area to facilitate micro-rotation. A standard plastic luer hub allows the trephine to be used with a syringe, either a standard type or one with a spring-assisted plunger. Scar tissue, biopsy specimens, or abnormal inflammatory fluids can be suctioned into the syringe for subsequent pathologic examination. PMID- 2250879 TI - The viscous fluid pump. AB - We describe a device useful for injection of viscoelastic material into the vitreous cavity for internal tamponade. The instrument has proven to be reliable and "user friendly" in a clinical setting. PMID- 2250880 TI - A new macula lens. PMID- 2250881 TI - Glaucoma gold: from Elliot's. A treatise on glaucoma. PMID- 2250882 TI - The White Pump Shunt. PMID- 2250883 TI - Molteno implant followed by penetrating keratoplasty in corneal graft failure and glaucoma. PMID- 2250884 TI - Corneal graft rejection in a child and inadvertent substitution of Tobrex for TobraDex. PMID- 2250885 TI - Visual acuity and contrast sensitivity of the S cone pathway: preliminary measures with letter charts. AB - Letter charts were used to measure visual acuity and peak contrast sensitivity of the short wavelength sensitive (S cone)-pathway. The accommodative response was monitored retinoscopically. The mean visual acuity (0.92 logMAR) and spatial contrast threshold (8.7%) were comparable to values reported elsewhere, and variability was relatively low. Both S-pathway acuity and contrast sensitivity were selectively reduced in one patient with central serous retinopathy and in another with retinitis pigmentosa. These simple spatial tests offer an additional index of S-pathway integrity which will be useful for detection and evaluation of ocular disease. PMID- 2250887 TI - Adsorption and removal of protein bound to hydrogel contact lenses. AB - Tear film proteins are known to adsorb to new hydrogel contact lenses. Using a radioiodine tracing technique, proteins were shown to adsorb to contact lens surfaces. The quantity of protein adsorbed to the contact lenses within 2 to 4 h was 1 to 3 micrograms/lens. The degree of protein adsorption varied from lens-to lens depending in part on the water content of the lens. High water content ionic lenses bound the most protein, whereas lower water content and nonionic lenses bound less protein. Enzyme cleaning of the protein-coated contact lenses removed about 75% of the adsorbed protein. When the enzyme-cleaned lenses were reincubated with protein, similar quantities were quickly readsorbed within a similar period of time. The rate of readsorption appeared to vary with the type of enzyme used to clean the lenses. Hydrogel lenses adsorb protein from the tear film rapidly and irreversibly. Cleaning the lenses has only a partial and temporary effect on the bound protein. The lens-bound proteins could become partly denatured during their binding to the lenses. These observations suggest a possible role for such proteins in ocular sensitivity to contact lenses. PMID- 2250886 TI - Meibomian therapy in problematic contact lens wear. AB - Utilizing the principal diagnostic criterion of an absent or cloudy Meibomian gland secretion upon repeated expression, patients with Meibomian gland dysfunction (MGD) were selected to participate in a study of the efficacy of lid scrubs and massage in the treatment of MGD. Twenty-one patients with contact lens intolerance unrelated to lens, care system, or health factors were randomly assigned to treatment of one eye with common clinical therapy for MGD. After 2 weeks of treatment, gland expression, biomicroscopy, staining, comfort, and fluorescein breakup time were assessed in a masked manner. Analyzed using a paired-data t-test, the results indicated a significant increase in mean tear film breakup time (BUT) in the treated eye at follow-up compared to baseline (mean increase = 4.0 s, p = 0.0001). The control eye demonstrated no significant change (mean increase = 0.2 s, p = 0.5955). These objective results were corroborated by reports of improved subjective comfort with contact lens wear after therapy. PMID- 2250888 TI - Visual acuity measured with clinical Maxwellian-view systems: effects of beam entry location. AB - Maxwellian-view projection systems are used clinically to evaluate visual acuity in cataract patients because they allow the clinician to direct a beam of light around any localized opacity. However, theory predicts that, as the beam is displaced from the visual axis, acuity will suffer with those instruments using white light due to the effects of ocular chromatic aberration. Using three commercially available Maxwellian-view instruments, we examined the decline of visual acuity with beam decentration in the clear pupil of normal subjects. With all three instruments (Lotmar interferometer, Randwal interferometer, and the Potential Acuity Meter) acuity fell by a factor of 3 for beams placed near the edge of a dilated pupil. Control experiments with monochromatic light indicated that lateral chromatic aberration was the primary cause of acuity loss with the two interferometers, but other off-axis aberrations also contributed to the acuity loss with the Potential Acuity Meter. A detailed analysis of the beam in the pupil plane indicates that the beam's complex structure may be altered if the beam strikes the iris or an opacity in the ocular media. These findings indicate that potential acuity may be significantly underestimated with polychromatic Maxwellian-view systems. PMID- 2250889 TI - Effects of disinfecting solutions on tonometer tips. AB - We investigated the effects of selected disinfecting solutions on the structural integrity of Goldmann applanation tonometer tips. Hydrogen peroxide, isopropyl alcohol, dilute sodium hypochlorite (household bleach), and glutaraldehyde phenate (Sporicidin) have been used for disinfecting tonometer tips. However, the effect of these solutions on the tips' structure has not been fully investigated. Haag-Steit tonometer tips were soaked separately for 30 days (723 h) in 5 different solutions and distilled water, approximately 1 working year of routine use (310 days by 14 patients per day). During the soaking period, the tips were regularly removed from solution, examined through a slitlamp, measured with vernier calipers, and photographed to monitor for structural degradation. Alcohol was the only solution that damaged the tips. The other disinfecting solutions appear to be safe for use on the tips after the equivalent of 1 working year of routine use. PMID- 2250890 TI - Simple clinical techniques to evaluate visual function in patients with early cataract. AB - Among the 80 subjects who were recruited with normal retinal and neural function, 54 had cataract and a visual acuity (VA) better than 6/24. The 26 age-matched subjects had clear media. Contrast sensitivity (CS) at low and intermediate spatial frequencies was measured using the Pelli-Robson letter chart. Two measures of glare disability (GD) were obtained using the Mentor Brightness Acuity Tester (BAT) in conjunction with a logMAR VA chart and the Pelli-Robson chart. Although CS is predominantly affected at high spatial frequencies in early cataract, we found that some subjects had reduced scores on the Pelli-Robson chart. This CS loss could not be predicted from VA measurements and was particularly found in subjects with posterior subcapsular cataract. High GD scores were found in a number of subjects with relatively good VA and could not be predicted from results of VA or CS. We suggest that CS and GD measurements using the Pelli-Robson chart and the BAT provide valuable information regarding the management of patients with early cataract. PMID- 2250891 TI - Normative contrast sensitivity data for young children. AB - Contrast sensitivity (CS) was measured in children ages 3 to 7 years using the Vistech Contrast Sensitivity distance chart (VCTS 6500). The purpose of the study was to determine how effectively the technique could be used with young children and to establish normative data for this age group. Of 286 children participating in a vision screening, the contrast sensitivity function (CSF) was measurable on 241 (84%) under binocular conditions and 229 (80%) under both binocular and monocular conditions. The 219 binocular CSF's and 208 monocular CSF's obtained from visually normal children were used to establish normative data and then compared to similar data from 50 visually normal young adults. The results indicated that there is an effect of age between 3 and 7 years, children are significantly less sensitive than adults, and adult-like levels of CS are not yet reached at 7 years of age. In addition, although the children's mean contrast thresholds fell within the norms provided with the VCTS 6500, the variability in the children's CSF's precludes using the Vistech data for diagnostic purposes in the young. The normative data are presented to assist the clinician in evaluating CS in young children when using the VCTS 6500. PMID- 2250892 TI - Survey of spectacle wear and refractive error prevalence in USAF pilots and navigators. AB - A retrospective survey of 5000 active aircrew records was performed at 12 United States Air Force (USAF) bases to obtain information about the prevalence of spectacle wear and refractive error. The data revealed that 27.4% of pilots and 51.5% of navigators/weapons systems operators (Nav/WSO) required spectacles when flying. Of the spectacle-wearing pilots, 12.4% required bifocals. Myopia was the predominant refractive error and a relatively large percentage of aircrew members had astigmatism of 0.75 D or more, e.g., 33.1% of pilots. At the time of entry into the USAF, refractive error data were clustered around emmetropia with a definite skew toward hyperopia. PMID- 2250893 TI - Orbital pseudotumor, differential diagnosis. AB - A 66-year-old white male presented with complaints of redness of his left eye, blurred vision, lid edema, and an intermittent throbbing pain above his left eye for 4 days. Significant clinical findings included mild hyperemia and edema of the left upper lid, marked engorgement and tortuosity of the conjunctival and episcleral vessels, mild chemosis, and extreme limitation of the extraocular movements of the left eye in all directions of gaze, especially adduction. This eye also showed a measurable proptosis with positive retropulsion. Pupillary responses and color vision were normal in both eyes. A CT scan revealed an enlarged medial rectus muscle, including its tendinous insertion with a normal cavernous sinus. On the basis of the clinical findings and the CT scan, a diagnosis of orbital pseudotumor was made. The patient was treated with high dose systemic prednisone, which resulted in a dramatic improvement of symptoms and signs. PMID- 2250895 TI - Sagittae of toroidal surfaces. PMID- 2250894 TI - True posterior ischemic optic neuropathy associated with herpes zoster ophthalmicus. AB - Although previous reports of ischemic optic neuropathy resulting from herpes zoster have appeared in the literature, these reports have not been convincing of a true optic neuropathy. The case presented is a true posterior ischemic optic neuropathy due to inflammation of the medial posterior ciliary artery, diagnosed on the basis of a deep, steep-sided altitudinal visual field defect. The herpes zoster infection also resulted in retinitis, damage to the iris sphincter, and corneal scarring. The effects of herpes zoster on the visual system are reviewed. PMID- 2250896 TI - Statistics notebook: entry I.L., theoretical aspects of three important cousins of the normal distribution, (1) The chi 2 distribution, (2) The t distribution, and (3) The F distribution. PMID- 2250897 TI - Is accommodative amplitude correlated with lens fluorescence? AB - We found a correlation between accommodative amplitude and lens fluorescence in a small population of subjects of nearly the same age. This supports the hypothesis that aging changes of the lens, including presbyopia, are related to lens growth. PMID- 2250898 TI - [The Tweed-Merrifield Edgewise technic]. PMID- 2250899 TI - [The temporomandibular joint: is it a joint like other joints? Joint pathology]. PMID- 2250900 TI - [The development and perspectives of the Edgewise technic. The therapeutic setting]. PMID- 2250901 TI - [The temporomandibular joint: is it a joint like other joints? Radiologic examination of the joint]. PMID- 2250902 TI - [Imaging of the temporomandibular joint]. PMID- 2250903 TI - [Biometry of the temporomandibular joint]. PMID- 2250904 TI - [The development and perspectives of the Edgewise technic. The biomechanics of the continuous arch]. PMID- 2250905 TI - [Metal technology and materials in Edgewise technic]. PMID- 2250906 TI - Membrane interactions of pp60v-src: a model for myristylated tyrosine protein kinases. PMID- 2250907 TI - The CD4 associated tyrosine protein kinase p56lck is positively regulated through its site of autophosphorylation. AB - Antibody-mediated aggregation of the CD4 T-cell surface antigen activates bound p56lck molecules and can result in increased intracellular tyrosine protein phosphorylation. To evaluate the basis of the CD4 induced tyrosine phosphorylation signal, we have studied the ability of CD4 to regulate the function of p56lck when these two molecules are co-expressed in non-lymphoid cells. Our studies indicate that cross-linking of CD4 is capable of activation of p56lck in fibroblasts in a manner analogous to that previously reported for T lymphocytes. They also demonstrate that replacement of the major site of autophosphorylation of p56lck (tyrosine 394) by a phenylalanine residue abolishes the ability to activate p56lck by CD4 cross-linking, implying that this residue is critical for the positive regulation of the Lck tyrosine kinase activity by CD4. Contrary to what we have previously reported for an antigen-dependent murine T-cell clone, as well as murine thymocytes, the CD4 induced activation of p56lck observed in fibroblasts does not result in marked changes in Lck tyrosine phosphorylation, suggesting that other lymphoid specific components may be required for these tyrosine phosphorylation changes. PMID- 2250908 TI - Properties of tripartite chimeras between Src and Lck. AB - To evaluate the possible regulatory effects of interactions between different domains of Src-family kinases, we have assembled five chimeric molecules containing parts of p60c-src (Src) and p56lck (Lck). Chimeras contained the N terminal portion, kinase domain or C-terminal tail from either of the parent molecules. None of the four full-length hybrid proteins induced morphological transformation of NIH3T3 cells, nor stimulated phosphorylation of cell proteins on tyrosine residues, suggesting that their protein-tyrosine kinase activities were repressed appropriately in fibroblastic cells. However, two hybrid proteins, SLS and SLL, containing the Src N-terminal region, Lck kinase domain, and either Src or Lck tail, respectively, inefficiently induced anchorage-independent growth. Sites of phosphorylation in these molecules were determined by two dimensional peptide mapping. SLS and SLL were both phosphorylated at their C terminal tyrosine residues similarly to the parental molecules. Curiously, both proteins were also significantly phosphorylated at tyrosine 416, a feature of transforming variants of Src and Lck. A modified hybrid, SLO, containing the N terminal region of Src, kinase domain of Lck and a truncated C-terminus, fully transformed cells and stimulated phosphorylation of cell proteins at tyrosine. Comparison of SLS, SLL and SLO suggests that the full-length hybrids are repressed by their C-terminal phosphorylated tyrosine residues in vivo. Consistent with this, SLO resembled activated Src in being cytoskeletal, and SLS and SLL resembled nontransforming Src and were not cytoskeletal. Hybrids with an Lck N-terminal region were cytoskeletal, like Lck itself, even though they were not transforming, suggesting that cytoskeletal localization of Lck is determined through its N terminus. Curiously, the hybrid molecules appeared not to be regulated in vitro. The specific activities of SLS, SLL and Src were approximately equal, but the specific activity of SLO was not increased, being much less than that of activated Src. Enzymatic dephosphorylation stimulated the in vitro kinase activity of parental Src, but not of SLS or SLL. These observations suggest that chimeric Src-Lck molecules are regulated in the cell, but not in vitro. PMID- 2250909 TI - Identification of a PDGF-responsive element in the murine c-myc gene. AB - The c-myc gene is rapidly induced in quiescent Balb/c-3T3 cells in response to the platelet-derived growth factor (PDGF). In order to study the mechanisms by which growth factors regulate induction of c-myc, we have attempted to identify growth factor-responsive elements in the murine c-myc locus. Various fragments of the c-myc gene linked to a bacterial CAT reporter gene were stably transfected into Balb/c-3T3 cells. A construct which includes the P1 promoter and 424 bp of upstream sequences shows a 3-5 fold induction of CAT RNA expression in response to sis/PDGF. S1 nuclease mapping experiments demonstrate that this mRNA initiates from the myc P1 promoter. Nuclear runoff transcription experiments performed with this myc/CAT construct show that this induction occurs at the transcriptional level. Deletion analysis led to the identification of an 81 bp segment in the first exon between the c-myc P1 and P2 promoters which is necessary to confer growth factor responsiveness in this construct. PMID- 2250910 TI - Molecular organization and differential polyadenylation sites of the human ETS2 gene. AB - The human ETS2 gene is a member of the ets gene family (ETS1, ETS2, ERG, ELK1 and ELK2) with amino acid similarity to the v-ets oncogene of the avian leukemia virus, E26. The ETS2 gene is composed of 10 exons, nine of which contribute to the open reading frame encoding 469 amino acids. The ETS2 gene directs the synthesis of three RNA transcripts, which differ from each other by the length of their 3' ends. This heterogeneity of 3' end is the major reason for the size differences between the transcripts, presumably reflecting utilization of three different polyadenylation signals/sites. The coding regions of all of the ETS2 RNA species are the same length and, thus, should contain the same open reading frame. PMID- 2250911 TI - Examination of the role of CSF-1 independence in myc retrovirus induced monocyte tumorigenesis. AB - These studies were initiated as an attempt to estimate the number and nature of genetic changes that are required in addition to c-myc deregulation during monocyte tumorigenesis, and to determine whether the oncogenic changes that can be created in vitro resemble the actual changes that occur in vivo. We found that superinfecting myc-immortalized monocytes with a colony stimulating factor-1 (CSF 1) expressing retrovirus strongly promoted tumorigenesis, whereas granulocyte/macrophage-CSF (GM-CSF) and v-fms retroviruses, or the spontaneous acquisition of CSF-1 independence did so only moderately. In addition myc infected monocytes isolated from mice at a stage prior to tumor formation are more tumorigenic than in vitro myc-immortalized monocytes, but they were still largely CSF-1 dependent, and were not as tumorigenic as reinnoculated tumor cells. In the simplest model only two oncogenic activations are required for monocyte/macrophage transformation, immortalization of the cells with c-myc and deregulation of the CSF-1 gene. However, not all mechanisms that result in loss of CSF-1 dependence lead to full tumorigenicity, suggesting that in vivo tumorigenesis may involve multiple secondary events including growth factor independence. PMID- 2250912 TI - Analysis by pulsed field gel electrophoresis reveals complex rearrangements in two MET alleles in a chemically-treated human cell line, MNNG-HOS. AB - We have previously shown that two alleles of the MET locus are independently rearranged in the chemically-treated human cell line MNNG-HOS. One allele is the TPR-MET oncogene which was activated by fusion of the MET locus on chromosome 7 with the TPR locus on chromosome 1. The second allele is found on a der(7)t(1;7)(q23;q32) chromosome and is characterized by a deletion of the amino terminus of the MET extracellular ligand binding domain. Here we present a pulsed field gel electrophoresis analysis which reveals that the two MET allele rearrangements in MNNG-HOS cells are more complex than originally thought. The breakpoint in MET on der(7) has been molecularly cloned and, unexpectedly, we found that rearrangement in this allele involves sequences derived from chromosome 2. Moreover, the rearrangement producing der(7) involves an inversion of the MET locus or a more complex alteration. Analysis of hybrid cells containing TPR-MET demonstrated that both the upstream and downstream portions of MET are conserved in this rearrangement and that oncogene activation occurred by an insertion of TPR sequences into the MET locus. These findings illustrate that when examined at the molecular level some chromosome abnormalities can be extremely complex and, thus, are of limited value in gene mapping studies. PMID- 2250913 TI - Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. AB - Using the polymerase chain reaction, we have amplified exons 5 and 6 of the human p53 gene from paired samples of tumour and blood DNA of 60 patients with sporadic breast tumours and from placental or tonsil DNA of 30 normal controls. The patients' DNAs were previously examined for loss of heterozygosity of markers distal to the p53 gene on chromosome 17p and tumour samples were assayed for p53 mRNA levels. Hydroxylamine modification of mismatched base pairs was used to identify mutations in the amplified product. We have directly sequenced many of the samples including all those with mutations and have identified the particular mutation in each case. Exons 5 and 6 code for amino acids 126 through to 224 and constitute approximately 25% of the total coding region of the gene. They encompass part of the SV40 binding region as well as 2 of 5 areas known to be highly conserved in evolution and mutations in this region have been shown to be associated with tumorigenicity. We have found mutations in 13% of the primary tumours (8/60), all of which show allele loss of markers in the 17p region. No mutations were found in exons 5 and 6 of 30 normal controls. Our results are the first to identify mutations in p53 in primary breast tumours. Since our analysis has so far been confined to only part of the coding region of the gene, it is likely that further studies will reveal a mutation frequency in excess of 13%. PMID- 2250914 TI - Allele loss from chromosome 17 in ovarian cancer. AB - In a number of human cancers genes capable of suppressing tumorigenicity have been identified and in some instances cloned. Successful isolation of such tumour suppressor genes has depended upon either the mapping of a locus which confers susceptibility to a specific tumour, or the finding of specific allele loss in the tumour cells of heterozygous individuals. In ovarian cancer it is known that a small proportion (approximately 5%) of tumours are due to inheritance (Lynch et al., 1989). However, as yet the locus responsible has not been mapped. The only incidence of allele loss in ovarian tumours reported is on the short arm of chromosome 11 using a c-Ha-ras I probe to detect an RFLP (Lee et al., 1989), and on 3p and 6 in a small number of cases (Ehlen & Dubeau (1990)). We describe here the results of analysis of 19 tumours for allele loss using a probe for a hypervariable locus on the long arm of chromosome 17. Approximately 77% (10/13) of tumours from informative patients showed complete or partial allele loss at this locus. Using a probe for the short arm of chromosome 17, 31% (4 of 13 informative patients) demonstrated allele loss at this position. These results suggest that possible involvement of more than one chromosomal locus in the development of ovarian cancer. PMID- 2250915 TI - AUUUA motifs are dispensable for rapid degradation of the mouse c-myc RNA. AB - Sequence determinants responsible for c-myc RNA rapid turn-over are localized within the 3' non-coding region which is mainly characterized by the presence of two polyadenylation signals and a high content in A and U. Although the AUUUA/UUAUUUA motif is commonly thought to specify a whole class of unstable RNAs coding for various onco-proteins and cytokines, site-directed mutagenesis showed that both of the two such sequences found in the mouse c-myc RNA are dispensable for rapid RNA degradation. Although less efficient than the whole 3' non-coding region, the last 50 nucleotides of c-myc RNA, mainly made up of U and A and devoid of AUUUA/UUAUUUA motif, are sufficient to confer instability to the coding sequence. PMID- 2250916 TI - Biochemical properties of the Drosophila EGF receptor homolog (DER) protein. AB - Antibodies recognizing the Drosophila EGF receptor homolog (DER) were used to define the biochemical properties of the protein. We show that DER is a glycosylated protein, with different processing patterns in Drosophila and mammalian cells, and confirm its localization in the plasma membrane with the predicted orientation. The receptor produced in transfected cells displays only a basal activity of in vivo tyrosine kinase autophosphorylation, providing a sensitive assay for ligands which may trigger DER. EGF and TGF alpha, which trigger the mammalian EGF receptor, did not increase the kinase activity of DER. PMID- 2250917 TI - Allele losses on chromosome 17 in human epithelial ovarian carcinoma. AB - 16 epithelial ovarian carcinomas (12 serous, 2 mucinous and 2 endometrioid) and 2 benign ovarian adenomas were studied using recombinant DNA technology to compare loci on chromosome 17 in germ-line and tumour DNA. Four polymorphic probes mapping to 17p and one mapping to 17q were used. There was a high frequency of allele loss on 17q/(77%) and a slightly lower frequency on 17p (69%). These findings probably indicate loss of tumour suppressor genes which are of fundamental importance in the genesis or progression of epithelial ovarian carcinomas. PMID- 2250918 TI - Changes in thermal and mechanical pain thresholds in hand amputees. A clinical and physiological long-term follow-up. AB - In a previous study, allodynia to cold and vibratory stimuli was found in the finger stumps of 24 patients with amputations, control values being obtained from fingers of the intact contralateral hand. When treated with regional intravenous guanethidine block (RGB), some of the patients only had short-lasting relief of symptoms, whereas others experienced a more long-lasting beneficial effect. In the present long-term follow-up study the patients were re-examined 6 years after the RGB treatment. The aim was to investigate whether the earlier symptoms and signs persisted, and whether there were any differences in these respects, between patients with long-lasting (group 1) and short-lasting relief of symptoms after RGB (group 2). All 24 patients were asked to answer a questionnaire concerning their clinical symptoms. In addition, 14 of them visited the laboratory for determination of thermal and vibration-induced pain thresholds. Comparisons were made with values obtained at the first examination before RGB treatment and with values from 14 healthy subjects tested in a similar way on 2 occasions with an interval of 8 years. Twenty of 23 patients reported that cold exposure still evoked stump pain. However, the threshold measurements showed that with time the patients had become more tolerant to thermal stimuli not only in the injured but also in the uninjured hand. A rise in pain threshold was also observed when vibration-induced pain was tested in the injured hand. There was no significant difference between groups 1 and 2. Similar changes in pain thresholds with time were not observed in the group of healthy control subjects. PMID- 2250919 TI - Recurrent pain, illness intrusiveness, and quality of life in end-stage renal disease. AB - Repeated episodes of headache and muscle cramp were hypothesized to contribute to increased patient perceptions of illness intrusiveness and to compromised quality of life. Standard measures of pain, illness intrusiveness, and quality of life were obtained on 2 occasions, each 6 weeks apart, from 100 end-stage renal disease patients. The impact of recurrent muscle cramps on perceptions of illness intrusiveness was conditional upon the occurrence of headache symptoms. Perceptions of illness intrusiveness were significantly higher when both muscle cramp and headache symptoms occurred during one or more assessment intervals as compared to when muscle cramps or headaches, only, occurred. Illness-related concerns and general feelings of pessimism were also significantly higher among patients who experienced recurrent episodes of muscle cramp. Although no direct relations were observed between pain and other quality of life indicators, previous research has documented a relation between illness intrusiveness and quality of life. Recurrent pain problems, thus, appear to contribute to increased illness intrusiveness and to reduced quality of life in end-stage renal disease patients. PMID- 2250920 TI - Health locus of control, gender differences and adjustment to persistent pain. AB - Locus of control (LOC) beliefs, long thought important in adjustment to persistent pain, were studied among 160 subjects (67 males and 93 females) referred to a comprehensive pain rehabilitation program. The subscale structure of the Multidimensional Health Locus of Control (MHLC) was factorially replicated in our sample. Three unique MHLC profile clusters were identified for both males and females. Among men, cluster assignment was related to age only. The younger male patients reported a stronger internal attributional style. Older male patients relied more heavily on both chance and powerful other factors. Among women, cluster assignment was related to the use of coping strategies. For example, patients with high internal scores only, reflecting a strong internal orientation towards self-management of health care needs, were more likely to utilize Information-Seeking, Self-Blame, and Threat Minimization coping strategies than patients with high scores on both the Internal and Powerful Other factors. It appears that the presence of both Internal and Powerful Other health attributional styles is associated with less frequent use of cognitive self management techniques. In understanding the LOC scores it is important to rely on pattern analysis of scores. Implications for clinical treatment are discussed. PMID- 2250921 TI - Neonatal facial and cry responses to invasive and non-invasive procedures. AB - Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures. PMID- 2250922 TI - Effects of lesions in the anterolateral columns and dorsolateral funiculi on self mutilation behavior in rats. AB - The possible role of the anterolateral columns (ALCs) and dorsolateral funiculi (DLF) in pain mechanisms was examined from the effects of lesions in these tracts (alone or combined) on tests for chronic deafferentation pain (autotomy) in rats. Spinal lesions alone (i.e., without denervation) in either ALC or DLF or combined DLF-ALC did not lead to any form of self-mutilation behavior. Cervical surgery, without spinal lesion, followed by limb denervation (sham) resulted in similar autotomy characteristics to those observed following limb denervation alone (control). Both results were considered as one set of controls. ALC lesions simultaneous with, or 1-2 weeks prior to limb denervation (ipsilaterally or contralaterally) produced significant delay in onset of autotomy and decrease in percentage of rats showing this behavior. DLF lesions followed by limb denervation produced significant acceleration of onset of autotomy and increase in percentage of rats showing this behavior. Combined DLF-ALC lesions with limb denervation produced intermediate effects between those observed following either ALC or DLF lesions alone. These results give further support to the concept that autotomy is related to rostral transmission of nociceptive information and that a spino-bulbo-spinal inhibitory loop involving the DLF and ALC is triggered by chronic deafferentation pain. PMID- 2250923 TI - Effects of chronic clomipramine on central DADLE antinociception. AB - Equipotent antinociceptive doses, as determined by a tail-flick response, for centrally administered (periaqueductal gray) morphine (M) and D-Ala2, D-Leu5 enkephalin (DADLE) were established as 5 micrograms and 19 micrograms, respectively. Chronic (28 day) subcutaneous infusion of clomipramine (CMI) via an Alzet minipump attenuated both central M-and DADLE-induced analgesia by day 15; attenuation persisted for the duration of the infusion (day 29). Within 7 days following removal of the pump, antinociceptive responses to M and DADLE returned to near pre-CMI levels. Our results indicate a similarity between M and DADLE with regard to attenuation of their antinociceptive action by chronic CMI. This attenuation may be due to decreased mu opioid receptor sensitivity or density resulting from chronic tricyclic antidepressant administration. PMID- 2250924 TI - Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies. AB - Transcutaneous cranial electrical stimulation (TCES) with high frequency (166 kHz) intermittent current (100 Hz: Limoge current) has been used for several years in cardiac, thoracic, abdominal, urological and micro-surgery. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long-lasting postoperative analgesia. We have confirmed these clinical observations in rats using the tail-flick latency (TFL) test to measure pain threshold. TCES was not found to modify the pain threshold in drug-free rats, but it potentiated morphine-induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 h before the drug injection and be maintained throughout the duration of its pharmacological action. TCES potentitation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. These findings were confirmed by blind tests of the efficiency of TCES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide). The analgesic effect of these 4 opiates (TFL as % of baseline without or with TCES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 micrograms; analgesic effect 152%, 207% with TCES) suggesting that TCES potentiation of opiate-induced analgesia is centrally mediated. PMID- 2250925 TI - The influence of warning signal timing and cognitive preparation on the aversiveness of electric shock. AB - Many medical and dental procedures are noxious. Finding an optimal way of warning patients concerning the aversive procedures could help them to cope better. A model for the effective use of a warning signal in coping with pain posited that a person needs enough time to be able to react and should possess the skills necessary to utilize the time effectively. It was felt that a very short warning period, e.g., 5 sec, could not be long enough, while a 180 sec warning period would in and of itself become aversive. Reactions to electric shock were obtained from 36 paid, volunteer subjects who were each tested on a within-subject, counterbalanced order at 4 different warning periods: 5, 30, 60, and 180 sec. The subjects were divided into 3 groups: (1) the experimental group was provided with a pretested self-instructional booklet to learn a variety of pain control techniques; (2) the placebo group was provided with a self-instructional booklet on citizenship; (3) the control group waited quietly for 13 min. No significant results were obtained for the different pain-coping conditions. Significant differences, however, were obtained for the various warning periods. Maximum skin resistance changes, higher ratings of pain and of anxiety were obtained for the 60 and 180 compared to the 5 and 30 sec warning periods. Maximum heart rate was obtained for the 30 sec warning. Results were discussed in terms of the psychological meaning of the various measures as well as their clinical implications. PMID- 2250926 TI - Does intravenous methadone provide longer lasting analgesia than intravenous morphine? PMID- 2250927 TI - [Prevention of secondary cataract by intracapsular administration of the antimitotic daunomycin]. AB - Pharmacological inhibition of capsule opacification e.g. using antimitotics such as daunomycin is a promising concept. Our own in vitro studies on cultured porcine lens epithelial cells have shown, that daunomycin penetrates the cells within at least 5 minutes. It possesses a low acute cytotoxicity and significantly inhibits epithelial cell proliferation at dose dependent concentrations ranging from 2.5 to 7.5 mg/l. In addition, in vitro studies on isolated pig corneas showed almost no corneal endothelial toxicity. After 10 resp. 30 min. exposure to 7.5 mg/l daunomycin, there was only 4.8 +/- 1.6 resp. 6.1 +/- 1.5% endothelial damage that dit not significantly differ from BSS serving as control. Encouraged by our clinical experience of good anterior segment tolerance of 7.5 mg/l daunomycin when used during vitrectomy in PVR, we started a prospective clinical trial to assess the effect to daunomycin on capsular opacification after ECCE with endo-capsular IOL implantation using the envelope technique. After agreement of the medical ethic commission we chose 6 patients with a mean age of 78 (72-83), no other ocular or general diseases and bilateral cataract of identical morphology and density. After written consent of the patients their first eye was operated using BSS as control. At least 4 weeks later the second eye was operated and received 0.5 ml of daunomycin (7.5 mg/l) applied during 5 minutes into the cleaned capsular bag, leaving the anterior capsular flap and a Healon filled anterior chamber to protect the surrounding intraocular structures. Mean postoperative control time actually is 12 (6-17) months for the controls and 10 (5-14) months for the eyes treated with daunomycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2250928 TI - [Effect of daunomycin on epithelial cells of the crystalline lens. Experimental and clinical study]. AB - Daunomycin action on human lens epithelial cells has been tested in vitro, with different exposure times. A clinical study on 30 eyes, operated on by the same surgeon, has been carried out according to the Cologne protocol. Cell cultures, with different techniques were grown. This demonstrates that Daunomycin can destroy the lens epithelial cells. We can not currently say what dosage and protocols are necessary to achieve a prevention of secondary cataract. PMID- 2250929 TI - [Differential photo-oculography of vertical and oblique movements]. AB - Up to now EOG has been the only method used to record ocular movements in daily practice. However such a mean has various drawbacks and limits. It has two main gaps: firstly for vertical movements because the interference discharges related with palpebral movements and blinkings; on the other hand for oblique movements because the unequal transmission of EOG potential towards the orbital rim. The differential photo-oculography perfected by Charlier et Buquet has been fitted and now can be easily used in clinical conditions. With this optical method, it exists a direct relation between the gaze direction and video signals of the eye. The authors point out the reliability of its results not only for horizontal movements, but also for vertical and oblique movements. This method allows a relevant analysis of all kinetic parameters whatever the moving axis may be. PMID- 2250930 TI - [Semi-automated quantification of MRI high signals observed in multiple sclerosis]. AB - MR T2 Weighted sequences on the brain demonstrate disseminated "high signal zones" (HSZ) in patients with Multiple Sclerosis; these morphological alterations are corresponding to the plaques. From the very beginnings of MR in 1981, everybody recognizes the main importance of this fact. MR appears as the most sensible exploration in patients with M.S. But the signal alteration is not specific; the clinical considerations and the evolution are requested. The aim of this work is to give a reference tool for evolutive evaluation of the disease. A work station with a specially developed software are presented. The HSZ thresholding is partially automatic. The edition of a cerebral mapping is developed. These results are discussed. PMID- 2250931 TI - [Arterial vascularization and innervation of the lacrimal gland. Apropos of 100 dissections]. AB - The authors report the different types of arterial vascularization and lacrimal gland innervation, noticed in 100 human orbits with arterial latex injected. The lacrimal artery may be unique, arising either from the ophtalmic artery, the most frequent case (vascularization of type I) or from the external carotid system (vascularization of type II): it is possible that 2 lacrimal arteries are simultaneously present, originating from the 2 carotid system (vascularization of type III). The lacrimal gland is innerved by the lacrimal nerve and by one or several nervous branches, originated from the maxillary nerve. 3 possibilities can be found: a zigomatic branch from the maxillary nerve makes a preglandular anastomosis with the lacrimal nerve; a real lacrimal loop, which may form either an intraglandular anastomosis or be completely independant of the lacrimal nerve. Sometimes, several zigomatic rami do exist. These different variations and their frequency are analyzed and referred to the literature. PMID- 2250932 TI - [Proliferation of retinal glia and excitatory amino acids]. AB - Kainic acid administered intravitreally induced mitogenic effects in the adult rat retina at doses ranging from 60 nm to 200 nm. Similar effects resulted from the injection of domoic acid at doses ranging from 20 nm to 400 nm, and ouabain. L-glutamate, N-methyl D-aspartate and quisqualate provoked similar cytotoxic effects, i.e., swelling and vasuolization of the outer plexiform, inner nuclear and inner plexiform layer, and cell pycnosis. The latter induced no mitoses. The use of Rompun ketamine as anesthetic blocked the mitogenic effects. The immunohistochemical labelling of both glial fibrillary acidic protein and S100 protein in the dividing cells and the location of dividing nuclei in the inner nuclear layer are arguments for their Mullerian nature. We suggest that the mitogenic effects could account for reactive gliosis observed in some clinical conditions. PMID- 2250933 TI - [Diffusion of O2 in the normal and the ischemic retina of miniature pigs]. AB - Transretinal PO2 profiles were recorded during normoxia and hyperoxia in normal and ischemic retinal territories in anesthetized miniature pigs using double barrelled recess type microelectrodes. In normoxia and hyperoxia the PO2 in the normal territory decreased from the inner retina and the choroid towards the mid retina, indicating that the choroid cannot supply O2 to the whole normal retina. Preretinal and transretinal PO2 measurements in ischemic territories following a laser occlusion of a retinal branch vein demonstrated that in normoxia the direction of PO2 gradients prevents O2 diffusing from the choroid to reach the inner retina. This explains why the ischemic territories are hypoxic. In the contrary, during hyperoxia the intraretinal PO2 gradient indicates an O2 flux from the choroid to the inner retina resulting to marked preretinal PO2 increase at the affected territories. We proposed the hypothesis that in the ischemic retinas the hyperoxia does not induce a rise of the O2 consumption of the outer retina. Hence hyperoxia could be a useful tool to restore the oxygenation of the inner hypoxic retinal layers. PMID- 2250934 TI - [The role of prostaglandins in the regulation of retinal blood flow]. AB - Hypercapnia causes vasodilatation of retinal arterioles. Prostaglandin E1, injected close to retinal arterioles from the vitreal side cause vasodilatation apparently similar to that caused by hypercapnia. An inhibitor of prostaglandin synthase (indomethacin) was injected into the ocular circulation. There was a reversible inhibition of the retinal vasodilatation normally induced by hypercapnia. Indomethacin injected close to retinal arterioles from the vitreal side causes reversible vasoconstriction and inhibits the vasodilatory effect of hypercapnia. It is concluded that prostaglandin E1 satisfies three criteria for a candidate for a mediator of hypercapnia-induced arteriolar dilatation. PMID- 2250935 TI - [Laser-Doppler velocimetry on the optic nerve head and hemorheology. Animal experiments. First results in humans]. AB - We study capillary microcirculation on the optic nerve head and its interrelation with blood rheological modifications. The mean maximal velocity has been evaluated in the capillaries of the rabbit optic nerve with a laser doppler velocimeter, in physiological conditions and after intravenous Dextrane 250 injections. Dextrane 250 increases red blood cells aggregation and induces blood hyperviscosity at low flow rates. This hyperaggregation is determined with a reflectometric method. Experimental results show a significant reduction of blood velocity when blood viscosity increases. In our present study, we compare blood capillaries flow rate in the optic nerve, between two groups: healthy humans and subjects suffering from glaucoma. The aggregation level is simultaneously measured for the two groups. First results seem to prove that blood flow rate decrease is associated with red blood cells aggregation increase for the second group. PMID- 2250936 TI - Microperfusion studies of normal retinal vessels. D-glucose transport. AB - An experimental model was developed to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from the kidney tubule studies. Inulin was used as the reference tracer and D-glucose as the test tracer. We found a concentration dependent flux of D-glucose from lumen to bath that increased as D-glucose concentrations in the lumen rose. The flattening of the hyperbolic curve at the higher D-glucose concentrations in the lumen appears consistent with the Michaelis-Menten equation (Km = 6 x 10(-3) M). PMID- 2250937 TI - [Our experience with clinical study of the eye in the near infrared region]. AB - An instrumental setup has been developed in order to perform a quantitative clinical study of the reflectance of ocular tissues in several spectral ranges of the visible and the near infrared. The images recorded at different wavelengths are obtained nearly simultaneously from a CCD camera adapted to a retinal camera and connected to a microcomputer. The results of their analysis after processing are described. Each different type of lesion exhibits a typical spectral signature, demonstrating the value of this noninvasive extra ancillary test to help the differential diagnosis and the follow-up of choroidal tumors. PMID- 2250938 TI - [Mitotic effect of the pigment epithelium]. AB - The authors suggest the production by the cultured RPE cell of one or more angiogenic substances. This activity is highly increased when RPE are cultured in poor conditions, either due to a poor medium or after having been challenged by a high number of rod outer segments. The mitotic factor appears heat-labile and trypsine sensitive, but not dialysable which suggest their biochemical nature to be a protein. PMID- 2250939 TI - [In situ hybridization on tissue section: a new method for studying the amacrine cells of the retina and the centers of the visual system]. AB - In situ hybridization of nucleic acid probes, encoding the key enzymes of the synthesis of neurotransmitters, with sections of retina is a new method giving complementary informations to the data obtained by immunocytochemistry and autoradiography. It will allow a better characterization of amacrin cells, whatever might be their type, and a refined understanding of their function. It is an accurate tool to investigate the mechanisms of retinal degenerations and spontaneous or experimental microphtalmia. PMID- 2250940 TI - [Significance of the digital image in the diagnosis and classification of macular drusen]. AB - Macular drusen, hard or soft, have been often observed at the early stages of age related macular degeneration. Clinically, it has been shown that soft drusen and macular subretinal new vessels are associated in a statistically significative manner. The question is to recognize and to determine drusen at greatest risk for developing choroidal neovascularization? To answer to this question, a method of digital images analysis of fluorescein angiography had been perfected. About ten eyes, preliminary results show, an objective and quantitative difference of the evolution of the grey level during the same angiogram between the different retinal structures. This method would bring a prognostic feature for the long term follow-up of patients with drusen. PMID- 2250942 TI - [Immunohistologic study of the epiretinal membranes in proliferative diabetic retinopathy and retinal detachment with vitreo-retinal proliferation]. AB - An immunohistological study was performed in specimens of epiretinal membranes obtained during surgery in patients with proliferative diabetic retinopathy or retinal detachment with proliferative vitreoretinopathy. Using immunostaining procedures, these membranes were found to contain great amounts of immunoglobulins and complement, as well as a strong expression of class II antigens. These results confirm the involvement of auto-immune phenomena in intra ocular proliferative diseases and the close relationship between the immune system and peptide growth factors. PMID- 2250941 TI - [Transforming growth factor beta in the vitreous of patients with epiretinal proliferation]. AB - Recent evidence suggests that TGF beta, a substance synthetized and released by Retinal Pigment Epithelial (RPE) cells, might play a role in fibrotic preretinal proliferation. We measured the concentration of this factor by radioreceptor assay in samples of vitreous obtained from 17 patients by vitrectomy. Seven had uncomplicated Retinal Detachment (RD) and 10 had either Proliferative Vitreoretinopathy (PVR) or Epimacular Membranes (EM). In the RD group, the mean concentration of TGF beta was 0.06 p mole/ml of vitreous, and in the PVR group, 0.21 p mole/ml. The total mitogenic activity of native vitreous and the amounts of a and b FGF in each sample were also measured, but were not different in the 2 groups. These results suggest that TGF beta is involved in the mechanism of excessive repair which characterises preretinal proliferation. PMID- 2250943 TI - [Role of growth hormone in proliferative diabetic retinopathy. Clinical and immunohistochemical aspects]. AB - The first part of this work deals with the various therapeutics with pituitary aims on ten patients with proliferative retinopathy. In the second part, the Growth Hormone involvement is considered, by the mean of IGF-I dosages in the serum and the vitreous of diabetic and non-diabetic patients. IGF-I is also sought in neovascular membranes by immunohistological methods. If radioimmunological dosages are negative, IGF-I deposits are found into new vessels wall. The significance of these immunohistological findings remains to be determined. PMID- 2250944 TI - [The eye of birds of prey. Electroretinographic and histologic approach]. AB - Birds are an excellent material for the study of retinal adaptation. In this work, the purpose of the authors is to analyse differences between electroretinograms of species of diurnal habits (Falconiformes) and electroretinograms of species of nocturnal habits (Strigiformes). The same is done on histology material about the two types of retina. The electroretinography answers and the retina histology can be correlated with the different species habits. PMID- 2250945 TI - [In vitro study of the effects of neodymium-YAG laser on silicone oil]. AB - Composition of gas generated by the utilisation of Nd-Yag laser in eyes filled with silicone oil were studied by means of an in vitro optical breakdown in silicone oil. The newly formed gas were analysed by headspace gas chromatography on two separate columns. The secondary gas were mainly methane and ethylene which might be potentially harmful to the ocular tissues. PMID- 2250946 TI - [Treatment of corneal edema using saturation of free radicals]. AB - We report on the results obtained in the treatment of inflammation of the cornea by means of the saturation of free radicals, using chemiluminescence. The experiment was conducted on the Alloxan model of corneal inflammation caused by the freeing of free radicals in the stroma. We compared the action of steroidal and non-steroidal antiinflammatory substances, and also specific saturators of free radicals. PMID- 2250947 TI - [Effect of retinoids on the growth of corneal endothelial cells in culture]. AB - Corneal endothelium is a target tissue for retinoids and epidermal growth factor (EGF). We report here that retinoic acid and its synthetic analog, CBS-211 A (10( 8)-10(-7) M), enhance the mitogenic effect of EGF on cultured bovine corneal endothelial cells (BCEC). Furthermore, retinoid treatment increases the EGF binding capacity of BCEC. The addition of cycloheximide (0.5 micrograms/ml) to cultures simultaneously with retinoids suppressed the retinoid effect on EGF binding. These results suggest that retinoids could induce the expression of EGF receptors on BCEC as an early event. This study demonstrates a cooperation between retinoids and EGF in corneal endothelium and suggests that retinoids could have a beneficial effect on this tissue repair in vivo. PMID- 2250948 TI - [HLA antigen expression of human cornea. Effect of organ culture preservation]. AB - The aim of this study is to examine the variation of HLA expression on organ cultured human corneas. Using an indirect immunofluorescence technique and monoclonal antibodies anti-HLA-A, B, C and anti-HLA-DR histocompatibility antigens were detected. In fresh corneas class I antigens were detected on epithelium and stroma but not on endothelium. Class II antigens were not detected on any corneal layer but were present on Langerhans cells within epithelium and stroma. The expression of HLA-A, B, C antigens within the corneal epithelium and the corneal stroma was not altered by 28 days of organ culture. HLA-DR antigens were present on Langerhans cells on corneas that had been in organ culture up to 14 days (present 6/9). After 14-28 days in culture Langerhans cells were not found on most corneas (present 3/12). Corneal preservation in organ culture at 31 degrees C affects expression of HLA antigens particularly of HLA-DR antigens. Combination of HLA matching donor-recipient with an 10-15 days organ cultured corneal button in high-risk patients seems to be of interest. PMID- 2250949 TI - [Human collagen IV lenses and epikeratoplasy in monkeys. Study of epithelial cicatrization]. AB - A previous study showed the good tolerance of the human type IV collagen lenses implanted by epikeratoplasty in 8 monkeys. It also showed type IV collagen is a good material for the reepithelialization. But we have been interested in the stability of the epithelial healing. The ultrastructural study found anchoring structures. However these were inconstant. So the authors try to understand better the mechanisms of this synthesis of the anchoring structures and describe the future ways of this experimental study. PMID- 2250950 TI - [Intraocular lens planning. Geometric-optical and Sanders-Retzlaff-Kraff I and II formulas]. AB - In the literature, curves based on the geometrical-optical (theoretical) formula and on regression formulas are established to show the superiority of a certain formula type in respect to the other formula type. Such curves are not based on the data of an individual eye needing an IOL implant, they are (more or less) mean value curves for a certain corneal curvatures and for a certain assumed postoperative position of an IOL. Due to the fact that Sanders, Retzlaff and Kraff suppose a normal corneal curvature, her curve for the theoretical formula gives in short eyes unrealistic and much too high values. A "more realistic" curve for the theoretical formula would be situated in the region of the so called "second generation formulas". All these mean value curves are unable to demonstrate the precision of IOL power formulas for the individual case. For the individual case refractive balances allow precise statements concerning the formulas and the measuring accuracy of the used a-scan. Refractive balances are the comparison of all preoperative data of an eye with all postoperative data including postoperative ultrasound measurings of the pseudophakic eye. Our results of 197 IOL implantations with refractive balances show the clinical precision of the theoretical formula. This is still valid in cases having unusual optical data, for example having short or long eye axes, having unusual corneal curvature or unusual IOL main plain position. PMID- 2250951 TI - [Comparative study of the tumor regression rate of 127 uveal melanomas irradiated with 106 Ru/106 Rh. Attempted analysis of the correlations between per-operative cytology and histopathology of the enucleated eye and the tumoral regression on the one hand, and general prognosis on the other hand]. AB - A study of the speed of tumor regression in 127 uveal melanomas treated with beta rays brachyterapy, since June 1983, allows a division into 2 groups: radiosensitive forms with a volume less than 50% in the following year, and radioresistant forms. Correlation between radio sensitivity and tumor cell type were obtained with intraoperative cytopunction, and showed the prevalence of epithelioid type. The results of enucleation indicate the prevalence of fusiform type inside the radioresistant tumor group. No precise correlation could be brought between death and the previous data, the most important negative criteria being the level of initial tumor height equal or superior to 7 mm. PMID- 2250952 TI - [Treatment of various malignant melanomas of the choroid using a combination of ruthenium 106 and cobalt 60]. AB - The association 106Ru/106Rh and 60Co was used to treat choroidal malignant melanomas with a height of 7 mm above the scleral surface (4 cases) and tumors unsuccessfully treated with a first 60Co plaque therapy (3 cases). The association of both radionuclides allowed a dose of 85 Gy at the apex of the tumor and of 700 Gy at least on the base in every case. All the patients were alive without evidence of metastases with a minimum follow up of one year and the tumor regression was constant and sometimes spectacular. PMID- 2250953 TI - [Maculopathy caused by irradiation in patients treated for choroid melanoma]. AB - We are using Cobalt 60 plaques at Curie Institute since 1968 for the treatment of malignant choroidal melanoma. We reviewed a series of 79 patients treated between 1982 and 1984 with a minimal follow up of 5 years. Tumors thickness varies between 2 and 11 mm with a mean thickness of 5.7 mm. All the tumors received at least 70 grays at the apex. 7 patients died from other cause, 7 patients presented metastasis 65 patients are alive and well, 49 of them have kept their eye and 16 have been enucleated. 18 patients have a visual acuity below 20/200 because of severe maculopathy, 29 patients have a visual acuity between 20/200 and 20/25. The most severe functional visual loss was due to maculopathy. It consisted of obliteration of the capillaries, exsudation and cystoid macular oedema. If we compare these results to other authors we see that maculopathy is a frequent problem with cobalt 60. For these reasons, we intend in the future to use iodine 125 plaques and prothontherapie that should give us better functional results. PMID- 2250954 TI - [Neuron-specific enolase in the aqueous humor. Its significance in the differential diagnosis of retinoblastoma]. AB - Several studies support that retinoblastoma originates from a primitive neuroectodermal cell, the main argument being the expression of the neuron specific enolase (NSE) by the retinoblastic cells. NSE was measured in the aqueous humor taken off: 1) in 19 patients with various eye disorders for which the diagnosis of retinoblastoma was definitely excluded (NSE = 5.0 +/- 7.7 micrograms/l); 2) at the time of the enucleation, in 7 cases of proved retinoblastoma (NSE = 83 to 17,900 micrograms/l); 3) in 2 cases of retinoblastoma held as cured for more than 5 years (NSE = 2.8 and 8.7 micrograms/l). The high level of NSE in the aqueous humor of the subjects with retinoblastoma is very significant, so that it can play a great part in the diagnosis, particularly in the case of atypic tumors. Specific indications of this determination may be considered for the survey of tumors under treatment or of the controlateral eye after a first tumor. PMID- 2250955 TI - [Prenatal diagnosis of various hereditary blinding diseases]. AB - The availability of more and more reliable obstetrical echographies makes now possible to screen fetuses for microphtalmies and anophtalmies. More over, by mean of linkage studies with DNA markers within a family, we can identify the women who will transmit X-linked diseases, and realize a prenatal diagnosis. This technology can be applied to the following ophthalmological diseases: the X linked retinoschisis, the choroideremia, the ocular albinism, the Noorie disease, and recently the retinoblastoma. From now on, the use of such a technology which makes it possible to detect ophthalmological diseases in the fetuses, is posing ethical problems especially in case of diseases without any survival prognosis involvement. PMID- 2250956 TI - [The Binder syndrome and goniodysgenesis. Apropos of a case]. AB - A 15 years old boy was deferred to our department with growth hormone deficiency, deafness with middle ear bones involvement, and a facial dysmorphy called Binder syndrome. He presented ocular abnormalities with juvenile glaucoma and iris anterior insertion and goniodysgenesis. All these pathologic features are linked with the development of the neural crests. In our knowledge, it is the first so complete clinical association reported, which emphasizes the important role of the neural crest cells in early organogenesis. PMID- 2250957 TI - [Development of the steady-state cortical visual evoked response in children]. AB - Steady-state VEPs responses (pattern reversal stimulation) have been studied by the application of frequency analysis with Fourier methods. Authors examined with this method a group of children aged from 4 to 12 years, without ophthalmological or neurological pathologies. Responses evaluation is based on the number of harmonic frequency components and also on the power spectra of the first two components. Frequency analysis shows a well proportioned responses development that can be considered as a good index of visual function growth. PMID- 2250958 TI - [Statistical results of 700 electrophysiologic tests (ERG) in patients without ophthalmologic manifestations treated with synthetic antimalarials for rheumatologic or dermatologic disease]. AB - 737 adapto-electroretinograms are registered on patients treated by chloroquine for a rheumatoid arthritis (RA) or for a lupus. Their ophthalmological examinations are completely normal. In term of the cumulative doses, the statistical results of the electrological characteristics of the different waves of the ERG issued from white, red and blue stimulations show: a great stability of the latencies of the "a" and "b" waves; a gradual decrease of the "b" wave amplitudes for the RA; a gradual increase of the "b" wave amplitudes till a level dose reached between 800 and 900 g and then a decrease of the "b" wave amplitudes, for the lupus. We discuss the electrophysiological criterions for a beginning intoxication. As a standard, for the R.A., it seems that a certain amount of "b" wave amplitude decrease could be admitted but the "a" and "b" wave latencies must be very constant. For the lupus, the hyper normality or at least stability of the "b" wave amplitude can be admitted till a dose around 800 g, associated to a good stability of the "a" and "b" wave latencies. Beyond these statistically established limits a beginning intoxication should be suspected. PMID- 2250959 TI - [Functional study in early strabismus: translucent screens and electro nystagmography]. AB - The symptoms of infantile strabismus are triggered by fixation, chiefly monocular fixation. On the excluded eye, "occlusion deviations" (elevation, esodeviation, extorsion) are well observed through a "translucent" unilateral cover. These deviations are super-imposed upon a position of rest without fixation which may be an orthoposition, well observed through bilateral translucent occluders. They are caused by a rupture of binocular retinal stimuli which does not mean rupture of fusion (ex: the darkening Bielschowsky test). Electro-oculographic studies confirm the prevalence of adduction during fixation (nystagmus, pursuit, optokinetic nystagmus). This directional asymmetry is typical of the infant's immature system of fixation. In infantile strabismus, it persists because of missing binocular links (corpus callosum--cortex----midbrain) as shown by the study of the so-called congenital monophthalm syndrome (unilateral congenital blindness). PMID- 2250960 TI - [Analysis of vergence movements using differential photo-oculography]. AB - Analysis of vergence troubles is weight by an heavy handicap. In clinical conditions it is easy to value the static vergence balance with a great lot of tests. On the contrary examination of kinetic vergence pattern is generally neglected. Usually a refixation vergence is a combination of an horizontal convergence-divergence of 5 to 10 degrees with a vertical component of 15 to 20 degrees. It is impossible to do their reliable analysis by kinetic EOG because the unequal transmission of potential towards the orbital rim. The authors give the results obtained by photo-oculographic method perfected by Charlier and Buquet. On all recordings it can be noticed that, in vergence refixation, vertical movements of both eyes are always true congruent saccadic versions, while the horizontal movements are disjunctive, dissociated and unequal. On the vertical axis it seems to be no real kinetic vergence at all, but in some cases only a mere tonic alignment. Such a device is a very good mean to study the vergence troubles in daily practice. PMID- 2250961 TI - [Automatic perimetry in screening programs]. AB - This work has studied the use of automatic perimetry in glaucoma screening programs. Subjects with suspicious glaucoma were selected on the basis of tonometry and direct ophthalmoscopy. Visual fields were analyzed using the G1 program of the Octopus 500 E automatic perimeter. A prevalence of 3.49% of glaucoma was observed in persons above 40 years old. This represents a higher incidence in comparison to other studies. The inclusion only of those subjects with suspicious glaucoma for automatic perimetry has resulted in a more precise and earlier diagnosis of glaucoma without unduly prolonging the duration of the study. Undoubtedly, automatic perimetry can improve both the reliability of the diagnosis and incidence of glaucoma in screening programs. Moreover, this does not necessarily mean more prolonged or costly studies. PMID- 2250962 TI - [Retinal nerve fibers and automated visual fields during the course of primary open-angle glaucoma]. AB - Retinal nerve fiber examination is confronted with the results of automatic exploration of visual field with Octopus. 99 eyes affected by open angle glaucoma were studied during a period of 4 years or less. Analysis is done in accordance with the course under therapy. Good pressure results are obtained. Meanwhile visual field indexes show a slow deterioration under medical treatment, a stabilisation after laser trabeculoplasty and a marked improvement after surgery (trabeculectomy). Retinal nerve fiber are clear prior affected in comparison with visual field in early glaucoma, and a perfect agreement is demonstrated in mature cases. PMID- 2250963 TI - [The central visual field in flicker stimulation]. AB - The authors reported their results of flicker visual field in ganzfeld and 17 central points with 3, 8, 15 and 35 Hertz flicker. They tested 4 groups of control subjects and 12 patients with glaucoma. The flicker visual field may be a useful aid in determining campimetric abnormalities for glaucoma patients with normal static perimetry. PMID- 2250964 TI - [Static microperimetry with the laser scanning ophthalmoscope]. AB - We have used the scanning laser opthalmoscope (SLO) with a personal computer to develop static microperimetry techniques. They allow to see in real-time on a television monitor the precise retinal localization of the stimulus and fixation. The testing is performed under strict conditions. The size of stimuli can vary between 6 and 30 minarc on a side. 255 different intensity levels are possible with the instrument. We have selected 12 of them, representing a logarithmic scale. Stimulus duration can vary between 50 and 500 ms. Examples of macular pathology including subretinal neovascularization, drusen and macular edema are given. PMID- 2250965 TI - [The perimetric score in Bjerrum's area]. AB - The authors have examined a protocole in automatic perimetry. On glaucoma they have measured, with different instruments, deficits in visual fields in Bjerrum's area. The perimetric score gives them a numeric data which determines rapidly the patient's state. This data may be used on graphics. PMID- 2250966 TI - [Immunologic diagnosis of ocular larva migrans syndrome]. AB - To elicit the differential diagnosis between retinoblastoma and ocular larva migrans, we have realized an immunological diagnosis detecting antibodies in the endoocular fluids, using gel precipitations methods (electrosyneresis, Ouchterlony, immunoelectrophoresis) with the antigens Excretions-Secretions of T. canis and T. cati larvae. We have got 8 positive results out of eight cases of ocular larva migrans and no false reaction out of 11 control sera. Theses methods appear to be better than E.L.I.S.A. because it is difficult to define the threshold value for this technic. PMID- 2250967 TI - [Humoral immunity and the argon-laser]. AB - We have done two argon-laser iridotomies 24 and 72 hours before cataract surgery, to study ocular inflammation. We have taken aqueous samples to study IgA, IgG, C3 and AAT by laser immunonephelometry. All the proteins raised in the first 24 hours (P less than or equal to 0.01) except IgA in aqueous humor, taken with control levels, but only AAT (P less than or equal to 0.05), albumine at 72 hours (P less than or equal to 0.01) in aqueous humor. We tried to understand the observed gap by immunomodulation of released mediators. PMID- 2250968 TI - [Morphometry (Sketch PC) of the corneal endothelium after injection of 5 fluorouracil into the anterior chamber]. AB - We made a study of the effect on the corneal endothelium of rabbits of the introduction of 5-Fluorouracile into the anterior chamber. An EECC was performed on 24 rabbits, using BSS-Plus for right eye and 5-Fluorouracile dissolved in BSS Plus for the left eye as irrigation solutions. We calculated the individual endothelial cell surface and form factor, finding no statistically significant differences between the two groups. PMID- 2250969 TI - [Theoretical study of the optical power of a cornea after keratophakia as a function of the depth of insertion of the lenticule]. PMID- 2250970 TI - [Hemorrhage in the premacular bursa treated with the Q-switched Nd-YAG laser]. AB - Hemorrhages in the premacular bursa may cause an important loss of the visual acuity due to their localization. Several treatments, going from a conservative attitude to prompt vitrectomy, have been proposed. Three cases of premacular hemorrhage, treated by Nd-YAG laser puncture, are reported. One or two impacts are sufficient to empty the blood collection into another vitreous compartment. The blood is dispersed through the vitreous on the second day after treatment and is resorbed within the ten to fifteen following days. With the help of ultrasound, the blood volume was estimated to be equal to or less than 10 microliters in the three cases. In all cases the YAG laser puncture allows a faster recovery of the visual acuity as compared to the conservatively treated cases. In no instance a recurrence, macular degeneration or preretinal proliferation was observed. The new concepts of vitreo-macular relations and vitreous anatomy are well illustrated by this therapeutic indication. Although the precise localization of a blood collection in the premacular area remains controversial, we consider it of no consequence to the outcome of the treatment. PMID- 2250971 TI - [Secondary divergence in esotropia. Effect of the initial surgical technique]. AB - The authors study two hundred observations of children with esotropia operated by recession of internal muscles associated or not with one or two loops. The indications are precise, then the secondary exotropia is studied. The technic doesn't seem to give more frequent exotropia than other surgical procedures if the initial protocol is right. PMID- 2250972 TI - [Chronic vitritis in pseudophakic patients]. AB - We present 15 cases of chronic endocular posterior inflammation, so called vitritis, following cataract surgery. All these cases occurred after uneventful extracapsular surgery plus posterior chamber intraocular lens implantation. Aqueous and a vitreous taps did not reveal any germ but they were done long after the onset of inflammation. Vitrectomy for optical purpose may be helpful for these patients. The two main complications have been retinal detachment and cystoid maculopathy. Retinal detachment can be cured but this requires quite often sophisticated surgical procedures. We found no effective treatment for cystoid maculopathy. PMID- 2250973 TI - The treatment of prolactin-secreting pituitary adenomas. An update. AB - Prolactin-secreting adenomas are the most common type of pituitary tumors. In this paper the Authors review the therapeutic strategies based on the distinction between micro- and macro-adenomas. PMID- 2250974 TI - Gastric angiography: data for oesophagogastroplasty. AB - A report is presented on an angiographic study of the gastric arterial system conducted on 20 human stomachs taken from cadavers during routine autopsies. The aim of the study was to define the anatomical bases for the supply of blood to the isoperistaltic gastric tubule in oesophagogastroplasty operations. The study reveals that on its own the right gastroepiploic artery cannot ensure adequate vascularisation of the gastric fundus. The importance of pressuring the right hand section of the vascular arch along the small curve was also noted and is due to the constant presence of major anastomoses at antral level with the right gastroepiploic artery. The study also revealed the constant presence of a direct intramural anastomotic circulation between the right and left gastroepiploic arteries. PMID- 2250975 TI - Experimental study on the correlation between cardiac function and ovarian hormones. AB - Results of the study of cardiac function carried out on young women during various phases of the menstrual cycle were correlated to those obtained after acute administration of progesterone. In all cases systolic time intervals reveals a reduction of mechanical systole and of preejection. Direct action progesterone on cardiac function by an unknown mechanism was confirmed. PMID- 2250976 TI - Free perforation of small intestine in adults. AB - In a 14-year period 15 cases of free perforation of the small bowel in adults were treated in our department. In two patients perforation was caused by a foreign body and in six by each of the following: duplication of the small bowel, Hodgkin's lymphoma, vasculitis and steroid treatment, intussusception, adhesions, diverticulum. All patients presented with the signs of diffuse peritonitis. One patient died before surgery. Of the 14 patients operated upon, 10 underwent resection and primary anastomosis and four suturing of the perforation. In six cases the etiology remains unknown even after surgical intervention and pathological examination. The mortality rate of the 14 operated patients was 7.1%. 78.5% of the patients were operated on within 24 hours of onset of symptoms, and early surgery is considered to be the most important factor in the low mortality rate achieved in this series. PMID- 2250977 TI - The femorofemoral bypass graft. Report of a 11-year experience. AB - A series of 62 femorofemoral bypass grafts (FFBG) is reported. The indication for this operation was unilateral iliofemoral occlusion with severe ischemia of the lower limb in poor-risk patients. Severe ischemia presented as rest pain and/or minor necrotic lesions to the foot fingers, while patients were defined poor-risk for aging and concomitant diseases advising major surgical procedures and general anaesthesia. Claudication was not considered as an indication for this operation, and this statement is discussed in detail reviewing the literature. Operative death rate was approximately 6.4% (4 subjects), due to acute renal failure, revascularization syndrome, cardiac arrest and pulmonary oedema. Twenty subjects had had a total of 33 previous vascular reconstructive procedures; this occurrence did not reveal any statistically significant consequences on long-term patency rate, although a difference was seen in favour of the patients who had not undergone previous vascular reconstructive procedures. In the group of patients who underwent FFBG as the first vascular procedure, five early occlusions occurred: three Fogarty catheter thrombectomies were successful. Cumulative patency rate was then 77% at 36 months in the series of 58 survivors. Rest pain was relieved in any instances and a satisfactory improvement of claudication was obtained. PMID- 2250978 TI - Effects of oxygen-ozone therapy on age-related degenerative retinal maculopathy. AB - The effects of oxygen-ozone therapy on 20 patients affected by age-related degenerative maculopathy have been studied. Visual acuity and eye fluorangiography were the parameters used in order to evaluate the efficacy of the therapy. Medical ozone was administered intravenously according to the technique called "ozonized major autohemoinfusion", the total amount of ozone ranging from 1,500 to 2,000 micrograms per session for a 4 months period. The results have indicated that the majority of patients showed an improvement of their ocular condition, suggesting continuation of this type of investigation on a larger group of people. PMID- 2250979 TI - The use of nimodipine (Nimotop-Bayer) in patients with chronic ischemic cerebral vasculopathies. Twenty-eight case reports. AB - Nimodipine therapy (30 mg x 3/die) was commenced in twenty-eight patients affected by chronic ischemic cerebral vasculopathies and continued for the 90 days in order to evaluate drug efficacy. Clinical controls were carried out 4, 8 and 12 weeks after the start of therapy using Doppler, ultrasound and neurological tests (the letter based on the SCAG neurological scale). Hemodynamic and hematochemical parameters were also monitored and controlled. PMID- 2250980 TI - Serum immunoglobulin status of psychiatric in-patients. AB - In view of the fact that substantial evidence today links psyche, brain, stress and immune system, the serum immunoglobulin (viz. IgG, IgA, IgM) levels in 40 patients with psychiatric disorders (viz. Schizophrenia, Affective disorder and generalized Anxiety disorders) have been investigated. With the exception of IgA, all psychiatric patients had significantly elevated IgG, IgM levels (p less than 0.001) when compared with healthy controls. Surprisingly these immunoglobulin levels irrespective of prevalent psychiatric disorder were almost similar to those of the hospitalized surgical patients pre-operatively (preferable controls), suggestive of no direct linear causal relationship between the psychiatric disorder and serum immunoglobulin levels. Factors affecting immunoglobulins have been discussed. Considering a probable viral association in Schizophrenia it is felt that simultaneous monitoring of viruses (affecting the nervous system) in the form of antigen/antibodies may be more informative. PMID- 2250981 TI - Elderly-animal postmortem attachment. AB - Attachment can be strong between people and their pets. The present study was conducted to determine: (1) specific variables associated with the final rite and disposition of the deceased pet, and (2) those criteria associated with emotional and social factors pertaining to elderly-animal postmortem attachment. Results suggested four most frequently stated variables of final rite and disposition, and eight emotional and social factors of elderly-animal postmortem attachment. PMID- 2250982 TI - Harlequin fetus: a case report. AB - The authors report a case of "harlequin fetus" which was brought to their attention. The report was justified not only by the rarity of the disease, but above all because, after having examined the literature on the topic, this appears to be the third case treated with etretinate. The case in question was a female affected by congenital ichthyosis in its total form and by initial necrosis of the extremities. Etretinate treatment gave good results in terms of cutaneous modifications: reduction of hyperkeratosis, disappearance of ectropion and eclabium. Therefore, although the patient died when 16 days old due to sudden renal insufficiency, the case confirms the two previous reports on the value of this therapy. PMID- 2250983 TI - Initial factors predicting functional performance in patients with traumatic tetraplegia. AB - The authors present a prospective analysis of the functional outcome in 99 patients with traumatic tetraplegia consecutively admitted to the Pellegrin Hospital (University Hospital, Bordeaux, France). There was a 29% death rate. Eighteen months after injury, 33% of the patients were dependent (not able to perform activities of daily living without the presence of a helping individual), 38% were independent. Two predictors of independence (age and initial Yale Scale Score) were found by a statistical analysis of the course of the disorder. PMID- 2250984 TI - The effect of intrathecal baclofen on the lower urinary tract in paraplegia. AB - The effect of intrathecal baclofen on urethral pressure was investigated in 6 spinal cord injured patients. Although the response was inconsistent, and further studies are necessary to define its role more clearly in the bladder management of these patients, its possible application as an alternative to sensory rhizotomy to improve bladder emptying in patients having sacral nerve stimulation procedures is discussed. PMID- 2250985 TI - Physical endurance capacity, functional status and medical complications in spinal cord injured subjects with long-standing lesions. AB - Seventy two spinal cord injured subjects (63 males and 9 females) with long standing lesions (mean 110 months, range 43-187) were admitted to the Sunnaas Hospital for routine examination (questionnaire, neurological status, radiography, urodynamics, blood specimen, and physical endurance capacity during armergometry). The subjects were divided into three groups with Low-(peak VO2 less than 15 ml/kg/min), Medium-(15 less than VO2 greater than 25) and High-(VO2 greater than 25) endurance capacity. The rate of urinary tract infections (UTIs) and osteoporotic leg bones, was significantly reduced with increasing oxygen uptake (p less than 0.05, X2 test). Differences in scores for ADL-independency (ADL = Activities of daily living) and ambulation on crutches with braces, were even more pronounced between the L, M and H groups (p less than 0.001). The same trends, although not always statistically significant, were also observed in a homogeneous group of paraplegic patients (n = 43, injury level below T6). The results emphasise the importance of regular physical endurance activities to patient well-being, because relatively high endurance capacity was found to be related to less frequent medical complications, and to a higher degree of ADL self-independency. PMID- 2250986 TI - Muscle release in the management of spasticity in spinal cord injury. AB - Muscle spasticity and contractures in the spinal cord injured are a big problem interfering with rehabilitation, leading to inconveniences and complications in these patients. Management is based on pharmacotherapy, physiotherapy and surgeries. The authors are against central neurosurgery except on rare occasions. They have been practicing peripheral surgeries chiefly on muscles and tendons with satisfactory results in selected cases. The guidelines and procedures are presented. PMID- 2250987 TI - Body composition and resting energy expenditure in long term spinal cord injury. AB - Body composition and resting metabolic rate (RMR) were measured in 4 spinal cord injured (SCI) paraplegic men. The level of lesion ranged from T4 to L1, and the duration of disability averaged 7.4 +/- 3.3 (SEM) years. Hydrodensitometry was used to determine percent body fat, fat mass and lean body mass (LBM). RMR was measured following a 12-hour fast and 24 hours post-exercise using a ventilated hood. RMR was also predicted from LBM values based on the equation of Cunningham (1980). Results of the body composition measurements indicated a greater than average amount of body fat for men of this age group. RMR and LBM were significantly correlated (r = 0.98, p less than 0.02). However, measured RMR values were lower than predicted in 3 of the 4 subjects, especially when LBM was relatively low. Further investigation into the relationship between LBM and RMR in SCI individuals is warranted using a larger sample size and with subjects representing a wide range of lesion level. PMID- 2250988 TI - Paraplegia from schistosomiasis. AB - Paraplegia, a rare complication of schistosomiasis has been reported in the literature. However, a detailed description of neurological recovery and long term functional follow-up has not been published. In the cases presented, one patient experienced slow recovery over several years and remains nonambulatory. The other patient, infected at the same time and place, has completely recovered neurologically. Recovery was independent of the rehabilitation efforts applied. Case reports, discussion of spinal cord injury due to schistosomiasis and recommendations for treatment are presented in detail. PMID- 2250989 TI - Chronic pain after spinal cord injury: an expedient diagnostic approach. AB - The reliability of distinguishing central, musculoskeletal, and syringomyelic pain by two points of history: (1) pain quality and (2) pain location relative to the level of paralysis in spinal cord injury patients was tested by (1) physical examination, and (2) by radiographic imaging. Fifty five incidents of chronic pain (median duration 10 years, range 3 weeks-42 years) were found in a survey of 66 spinal cord injured patients. Central pain was suggested in 24 patients on the basis of a predominant 'neurogenic' pain quality: burning, stabbing, needles and pins, or numbness; and a location at or distal to the level of paralysis. Neurogenic pain was not associated with structural pathology in these patients. Musculoskeletal pain was suggested in 20 instances on the basis of predominantly aching pain and a location at or distal to the level of paralysis. Aching pain was associated with degenerative joint disease (11 each); scoliosis, shoulder dislocation, contractures (2 each); fracture, soft tissue calcium deposit (1 each) in 19 patients. Syringomyelic pain was suggested in 11 instances solely on the basis of pain location above the level of paralysis. Magnetic resonance imaging revealed extensive syringomyelia in 8 patients. It is proposed that the quality and location of chronic pain can quickly suggest confirmatory examinations, sometimes revealing correctable causes. PMID- 2250990 TI - Timing of fracture fixation: a review. AB - The timing of fracture stabilization has received little attention in the current orthopaedic literature. The existing data on fracture fixation will be reviewed specifically with regard to early versus delayed stabilization. Timing relative to the multiple trauma patient, open fractures, periarticular fractures, and hip fractures requires special consideration. PMID- 2250992 TI - A dressing for repair of acute nail bed injury. AB - The use of a temporary metal foil stent after primary repair of acute nail bed injuries is a simple and dependable method for restoration of the smooth nail bed. The stent prevents adherence of the proximal nail fold to the underlying matrix, promoting patient comfort during subsequent dressing changes. PMID- 2250991 TI - The tethered spinal cord. Etiology and clinical manifestations. AB - Tethering of the spinal cord is frequently associated with myelomeningocele. However, orthopaedic surgeons must be familiar with the primary tethered cord, which is associated not with an overt myelomeningocele but with more subtle clinical findings, particularly in the pediatric patient. The charts of patients with tethered spinal cords from the Honolulu Unit of the Shriners Hospital for Crippled Children are reviewed to highlight potential diagnostic and treatment problems. Tethered spinal cord should be considered in the differential diagnosis of patients who present with isolated lower extremity deformities and/or subtle neurologic findings. Appropriate evaluation may require magnetic resonance imaging, ultrasonography, or metrizamide computed tomography. Urologic function must also be evaluated and monitored. The literature supports an aggressive diagnostic and, where indicated, surgical approach to the tethered spinal cord. Diagnosis and treatment at a young age has been shown to correlate with optimal results. PMID- 2250993 TI - The pronator compression test revisited. A forgotten physical sign. AB - Pronator compression testing is a valuable clinical feature of median nerve entrapment diagnosis. Of 10 patients with this disorder, all developed paresthesias preoperatively in the hand after 30 seconds or less of manual compression of the median nerve at or near the pronator muscle. Eight patients had a positive Tinel's sign at the impingement site, but only one patient had a positive electromyographic result. More than 50% of the patients had undergone previous carpal tunnel release or were diagnosed at presentation with double crush syndrome. All patients had a good or excellent result from surgical decompression of the median nerve in the forearm, except for one workers' compensation case who had excellent postoperative strength testing but multiple residual complaints. Pronator compression testing is a helpful and dependable physical sign in the diagnosis of pronator syndrome. PMID- 2250994 TI - Necrotizing myonecrosis and polymicrobial sepsis. The role of adjunctive hyperbaric oxygen. AB - A 19-year-old man, who was involved in a motorcycle accident, sustained a combined bony and vascular injury to his right lower extremity that required emergency surgery. Postoperatively, the patient developed a life-threatening, necrotizing, soft-tissue infection and sepsis. Hyperbaric oxygen therapy was used with surgery and antibiotics to control this rapidly progressive infection and to limit the extent of debridement needed. It was found to reverse the patient's deteriorating status and to halt the progression of the necrotizing infection. The scientific evidence for the use of hyperbaric oxygen in such cases is discussed. PMID- 2250995 TI - Osteoid osteoma of the hip: an alternate method of excision. AB - An osteoid osteoma of the femoral neck was successfully excised with a modified core decompression technique. The procedure is superior to the standard methods of excising lesions from the femoral head and neck region of the hip. A discussion of the exposure techniques, excision methods, and incidence of complications is presented. Osteoid osteoma of the hip is a common, benign bone lesion. While much has been written concerning its clinical, roentgenographic, and pathologic features, few articles directly address the technical difficulties in excising lesions from this area. The case presented describes a method of excising an osteoid osteoma from the femoral head and neck areas. PMID- 2250996 TI - Tips of the trade #29. Femoral windows for easy cement removal in hip revision surgery. AB - Long-stem noncemented revision implants allow the creation of large windows for removal of cement distal to a primary stem tip. If the window is cut so that it can be wired back in place, the femur is proximally and distally protected with cerclage wires, and a long noncemented revision stem is used to bypass the defect, the window can heal rapidly and without complication. PMID- 2250997 TI - Imaging rounds #104. Congenital dislocation of the patella. PMID- 2250998 TI - Sonographic features of benign intraperitoneal lipomatous tumors in children- report of 4 cases. AB - Four children with benign intraperitoneal lipomatous tumors (mesenteric lipoma, mesenteric lipoblastoma, omental lipoblastoma and mesenteric mesenchymoma) are reported. The ultrasonographic findings of these unusual pediatric masses are described and correlated with their conventional radiologic and pathologic appearance. The pre-operative diagnosis of these entities can be suggested by these features. PMID- 2250999 TI - Lenticulostriate vasculopathy in infants with infections of the central nervous system sonographic and Doppler findings. AB - Eleven infants had echogenic stripes in the basal ganglia at the location of the lenticulostriate arteries, seen by head ultrasound. Eight patients had proven infection with rubella (2 patients), cytomegalovirus (2 patients), syphilis (1 patient) or bacterial meningitis (3 patients). Two had probable intrauterine infection clinically, but the organism could not be identified; one had trisomy 13. A recent report correlated these echogenic stripes in patients with viral and syphilitic intracranial infection with pathologically proven mineralizing vasculopathy. Our group manifests a wider range of intracerebral infection associated with this finding. Duplex sonography performed in four infants showed these stripes in vivo to be arteries in the basal ganglia. The lenticulostriate arteries are not normally visible by grey scale sonography but their Doppler signal may be elicited in normal children and they are rendered vividly visible by color Doppler. Echogenicity of these vessels is highly suggestive of intracranial infection because it is not encountered normally or in babies with non infectious intracranial disorders except trisomy 13. The prognostic significance of this finding is yet to be determined. PMID- 2251000 TI - Horseshoe lung: differential diagnosis. AB - A detailed radiologic and anatomic study of one horseshoe lung syndrome has already been published from this centre. A further case of horseshoe lung, which was also diagnosed prospectively by radiology, is described. Alongside, this is a set of a group of three conditions: we describe a right accessory lung with a peculiar feeding arterial branch originating from the left basal pulmonary artery. The bronchogram and oesophagogram of this case were normal. The other is a case of bridging bronchus where the left lower lobe bronchus originates from the right main stem bronchus. This was discovered at post mortem bronchogram performed on a 19 weeks foetus. Finally, in the dog, we found that the pulmonary angiogram and bronchogram display close similarity to human horseshoe lung though the dog has two separate lungs. The common denominator of all above cases is the presence of a pulmonary arterial branch or bronchus crossing the midline from the ipsi to the contralateral side. Therefore, it may be concluded "in contradiction to the common belief" that pulmonary angiography or bronchography alone is not sufficient for the diagnosis of horseshoe lung. When only one of these investigations is available, computerized tomography is necessary to show the isthmic lung tissue before the diagnosis of horseshoe lung is confirmed. PMID- 2251001 TI - Idiopathic infantile arterial calcification: unusual features. AB - Idiopathic infantile arterial calcification (IIAC) is a rare disease of unknown etiology, which causes widespread arterial calcification and usually leads to early death from coronary arterial occlusion. Periarticular calcification has been reported in some cases. Two new cases are reported. In addition to the usual features of the disease, one was found to have ear-lobe calcification and the other an aortic aneurysm and coarctation of the aorta. Therapy with diphosphonate was apparently successful in one patient. PMID- 2251002 TI - Familial superior mesenteric artery syndrome. AB - Five members of a family of eight, including the father and four daughters, presented with symptoms previously attributed to the superior mesenteric artery syndrome. The four daughters also had radiographic studies supporting that diagnosis. This familial clustering raises the possibility of a genetic predisposition to this symptom and radiographic complex. PMID- 2251003 TI - Percutaneous transgastric drainage of the lesser sac in children. AB - In four children (5-14 years old), lesser sac fluid collections (3 pseudocysts and 1 abscess) were externally drained using a percutaneous transgastric approach. With ultrasound or CT guidance and fluoroscopic monitoring, a sheathed needle is inserted through the stomach into the lesser sac fluid collection, the catheter is exchanged, secured in place and connected to external drainage. All four fluid collections were complications of pancreatitis (3 acute post traumatic, 1 post-surgical). All four fluid collections were successfully drained without need for surgical intervention. There were no major complications. Three minor complications occurred as a result of reinsertion of catheters: transient gastric venous bleeding, hematuria, and bleeding into the pseudocyst. Percutaneous transgastric drainage can be performed successfully in children, and provides an alternative to surgical intervention of lesser sac fluid collections. Drainage early in the course of pancreatic pseudocysts may lessen the morbidity, potential mortality, and prolonged hospitalization usually necessary for standard medical and surgical management of these patients. PMID- 2251004 TI - Radiographic findings in hereditary multiple exostoses and a new theory of the pathogenesis of exostoses. AB - Analysis of 330 exostoses in 18 patients affected by hereditary multiple exostoses disease suggested a new classification of exostoses as eccentric or full-thickness. Radiographically arrest of metaphyseal remodeling with failure of coning and persistence of the primary metaphyseal trabeculae was evident in full thickness exostoses. Similar bone lesions can be obtained experimentally with inhibitors of bone turn-over. A localized, peripheral defect in remodeling over a limited time can give a satisfactory explanation also for the origin of eccentric exostoses. The thesis that this is the basic mechanism of exostosis formation is presented. PMID- 2251005 TI - Osteopenia and phenylketonuria. AB - Trabecular bone mineral content was assessed by quantitative computed tomography in eleven young adults with phenylketonuria who had been treated from early childhood with a diet restricted in natural protein and supplemented with amino acids, minerals and vitamins. There was a significant reduction in the bone mineral content of patients compared with the normal population. Prospective studies are indicated in younger patients to ensure optimum bone mineralisation is achieved by adulthood. PMID- 2251006 TI - Mucocele of paranasal sinuses in a young infant with cystic fibrosis. AB - We report the case of an infant who developed severe nasal obstruction as an unusual first presentation of cystic fibrosis (CF). Computed tomography (CT) showed homogeneous opacification of the symmetrically enlarged paranasal sinuses that gave the clue for the final diagnosis. PMID- 2251007 TI - Ultrasound findings in post-operative jejunojejunal intussusception. AB - The case is reported of an 11-year-old boy, who developed bowel obstruction after surgical exploration of a kidney transplant. An ultrasound study showed a jejunojejunal intussusception. PMID- 2251008 TI - Transient cerebellopontine demyelinisation revealed by MRI in acute cerebellar ataxia. AB - An eight year old boy was admitted to our ward with a history of abrupt onset of rapidly progressive gait disorder, nausea, vertigo and vomiting. The clinical as well as the laboratory findings suggested the diagnosis of acute cerebellar ataxia. Magnetic resonance imaging (MRI), however, showed marked demyelinisation in the cerebellar region and visual evoked potentials were pathologic. After immunosuppression the patient promptly improved clinically and the lesions depicted by MRI disappeared almost completely. PMID- 2251009 TI - Horseshoe lung without respiratory distress. AB - A case of horseshoe lung associated with scimitar syndrome is reported. The patient, a six year old boy, had no respiratory distress. Plain chest film showed hypoplasia of the right lung and scimitar vein. Angiography demonstrated that right inferior pulmonary arteries crossed the midline and reached to the left lung base. PMID- 2251010 TI - Inferior right hepatic veins: MR assessment of prevalence and potential clinical significance in children. AB - The prevalence of Inferior Right Hepatic Veins (IRHVs) in 82 children who had magnetic resonance imaging (MRI) of the abdomen was assessed. IRHVs larger than or equal in size to the Superior Right Hepatic Vein were found in 23% (19/82). In two patients with radiological evidence of Superior Hepatic Venous occlusion and without radiological evidence of portal hypertension, venous drainage was accomplished via large IRHVs. The findings suggest that, in children, IRHVs may act as efficient collaterals and help protect the liver from the consequences of high IVC obstruction. PMID- 2251012 TI - Familial subluxation of the metacarpophalangeal and proximal interphalangeal joints of the little finger in two consecutive siblings: the "serpentine little finger". AB - Two consecutive siblings, both males, presented with congenital curly little finger ('serpentine finger') caused by subluxations at the metacarpo-phalangeal and the proximal interphalangeal joints. Literature on this phenomenon is scant, and to the best of the authors' knowledge it is probably a new entity. A theory of the possible aetiology is presented. PMID- 2251011 TI - A case of Dandy-Walker malformation associated with occipital meningocele, microphthalmia, and cleft palate. AB - We present a case of Dandy-Walker malformation associated with occipital meningocele, microphthalmia, and cleft palate. Small numbers of cases of Dandy Walker malformation with occipital meningocele have been described in the literature, but to our knowledge, non of these also had microphthalmia or cleft palate. This association suggests that time of intrauterine origin of Dandy Walker syndrome was in the sixth or seventh embryonic week. In the diagnosis, both CT cisternography and direct neurosonography over the occipital meningocele was useful for the demonstration of a posterior fossa cyst which communicated with the fourth ventricle and the occipital meningocele. PMID- 2251014 TI - The doughnut sign. PMID- 2251015 TI - Behavior in Klinefelter syndrome, or where there is smoke there may not be a fire. PMID- 2251013 TI - A new syndrome with cerebro-oculo-skeletal-renal involvement. AB - We report on an infant male who presented with microcephaly of prenatal onset, schizencephaly, decorticated disturbance of the neurological function, congenital optic atrophy, abnormal eye movements and nystagmus. In addition, he had a skeletal dysplasia with predominant acromelic involvement and a renal disease characterized by both nephritic and nephrotic changes. The natural history of his condition included severe postnatal failure to thrive, lack of development of psychomotor milestones, intractable seizures, terminal renal insufficiency with early death. Such spectrum of phenotypic abnormalities has never been reported before and we suggest that it may represent a new syndromic entity. The differential diagnosis with the oculo-skeletal-renal syndromes, with the osteodysplastic primordial dwarfism of the Taybi-Linder type and with the Hutterite cerebro-osteo-nephrodysplasia, is discussed. PMID- 2251016 TI - Periventricular leukomalacia (PVL) and myelination. PMID- 2251018 TI - Are we becoming a two-class society based on neonatal circumcision? PMID- 2251017 TI - Daytime urinary frequency. PMID- 2251019 TI - Blood pressure and intraventricular hemorrhage in premature infants. PMID- 2251020 TI - More on meconium aspiration. PMID- 2251021 TI - Annual summary of vital statistics--1989. AB - US infant mortality continued to decline slowly and the provisional 1989 rate, 9.7 per 1000 live births, was the lowest ever recorded. Final 1988 data showed no change in cause of death distribution or in the wide discrepancy between white and black infant mortality. State rates varied from 6.8 in Vermont to 12.6 in Georgia. Worldwide, the US rate of 10.0 was bettered by 21 other countries, with Japan lowest at 4.8. Births increased in number and rate, because of a higher fertility rate and more women in the childbearing years. The birth rate to mothers 17 years of age and younger increased again. The proportion of women who had no or inadequate prenatal care was essentially unchanged. Deaths, crude death rate, and age-adjusted death rate decreased. The excess of births over deaths added almost 1.9 million persons to the US population, the highest rate of natural increase since 1971. The marriage rate was essentially unchanged, whereas the divorce rate decreased slightly, to the lowest level since 1973. With the exception of human immunodeficiency virus infection, homicide, and pulmonary malignancies, rates for most causes of death declined from 1988 to 1989. In comparison with 1940, most declines were substantial, led by pneumonia, down about 80%, and perinatal conditions, down about 75%. The only large-scale increases among major causes in the half century were in two diseases related to cigarette smoking: chronic obstructive pulmonary disease, up eightfold, and respiratory cancer, up almost sixfold. Death rates from all other cancers, as a group, decreased by some 20% and from cardiovascular diseases by some 60%. PMID- 2251022 TI - Efficacy of tetracaine-adrenaline-cocaine topical anesthetic without tetracaine for facial laceration repair in children. AB - To determine whether the tetracaine component traditionally used in tetracaine adrenaline-cocaine (TAC) is necessary to obtain effective topical anesthesia, a prospective study was performed to compare TAC and adrenaline-cocaine preparations for the repair of facial lacerations in children. Physicians were "blind" to which preparation was being used. Of 55 patients studied, 24 received TAC (103 sutures placed) and 31 received adrenaline-cocaine (151 sutures placed). The anesthetic efficacy of each preparation was approximately 95%; there were no adverse reactions related to administration of either medication or complications of wound healing noted in either group. The tetracaine component of TAC is superfluous for obtaining topical anesthesia of minor dermal lacerations of the face in children. The TAC formulation can be simplified by omitting tetracaine without compromising anesthetic efficacy. PMID- 2251023 TI - Increasing incidence of varicella hospitalizations in United States Army and Navy personnel: are today's teenagers more susceptible? Should recruits be vaccinated? AB - Hospital records for 10,687 United States Army and Navy adult varicella (chickenpox) admissions were reviewed. Annual hospital admission rates for varicella increased more than fourfold in the active-duty army during 1980 to 1988 and more than 18-fold among active-duty navy enlisted personnel during 1975 to 1988. Fifty-seven percent of varicella admissions occurred in the most junior military members, aged 17 to 20. More than half of the total varicella admissions occurred in personnel with less than a year of military service. Multivariate analysis of the navy data confirmed increasing time-related trends of risk, suggesting a national temporal trend of increased varicella susceptibility in US teenagers and young adults. Administering a safe and effective varicella vaccine to army and navy recruits could prevent more than 7260 hospital-bed days during the first year of use. PMID- 2251024 TI - Breast-feeding and diarrheal morbidity. AB - This study used a unique longitudinal survey of more than 3000 mother-infant pairs observed from pregnancy through infancy. The sample is representative of infants from the Cebu region of the Philippines. The sequencing of breast-feeding and diarrheal morbidity events was carefully examined in a longitudinal analysis which allowed for the examination of age-specific effects of feeding patterns. Because the work controlled for a wide range of environmental causes of diarrhea, the results can be generalized to other populations with some confidence. The addition to the breast-milk diet of even water, teas, and other nonnutritive liquids doubled or tripled the likelihood of diarrhea. Supplementation of breast feeding with additional nutritive foods or liquids further increased significantly the risk of diarrhea; most benefits of breast-feeding alone or in combination with nutritive foods/liquids became small during the second half of infancy. Benefits of breast-feeding were slightly greater in urban environments. PMID- 2251025 TI - Accidental poisoning with a superwarfarin compound (brodifacoum) in a child. AB - The "superwarfarin" compounds are 4-hydroxy derivatives of coumarin that have increased activity and a longer duration of action than the parent compound. The superwarfarins are used widely in the United States as rodenticides and are effective against warfarin-resistant strains of rats. A chronic accidental ingestion of one of these products, brodifacoum, by a 7-year-old child who had bleeding and laboratory evidence suggestive of a vitamin K-related coagulopathy is reported. The bleeding manifestations were severe and prolonged, requiring 13 months for normalization of coagulation times. With a negative history of ingestion and despite clinical suspicion, documentation of superwarfarin poisoning was hampered by the lack of readily available assays for these compounds, even from the manufacturers. Brodifacoum was also identified in rat feces from the family home. This finding raises the concern of poisoning not only from ingestion of brodifacoum particles themselves, but also from a fecal-oral route. A review of the literature is presented and the implications of this case for the practicing physician are discussed. PMID- 2251026 TI - Diagnosis and management of infantile marfan syndrome. AB - Marfan syndrome is infrequently diagnosed early in infancy. The experience of the authors with 22 severely affected infants diagnosed as having Marfan syndrome in the first 3 months of life is described and the literature on 32 additional infants with Marfan syndrome is reviewed. It was found that serious cardiac pathology (82% of the patients described in the article, 94% of those described in the literature) may be present at birth, and that congenital contractures (64% of our cases, 47% of literature cases) are often an associated finding. Other useful clinical findings included arachnodactyly, dolichocephaly, a characteristic facies, a high-arched palate, micrognathia, hyperextensible joints, pes planus, anterior chest deformity, iridodenesis, megalocornea, and dislocated lenses. Echocardiography was useful as a noninvasive method for defining the extent of cardiovascular involvement and following its course. Characteristic cardiac findings in early life included mitral valve prolapse, valvular regurgitation, and aortic root dilation. Cardiac function ranged from normal to poor, with a tendency to worsen. Of the 22 cases 3 infants died during the first year of life. Morbidity and mortality may be high when Marfan syndrome is diagnosed during infancy, and prompt recognition of this phenotype can facilitate management and counseling. Most such severe cases appear to be due to a sporadic mutation in a single germ cell of one parent. Many familial cases may have milder manifestations, be more difficult to detect during infancy, and have a better prognosis. PMID- 2251027 TI - Behavioral risk, emotional risk, and child abuse among adolescents in a nonclinical setting. AB - In this replication study of adolescents in a nonclinical setting, the prevalence of reported problem behaviors, emotions, and abuse is evaluated, and the impact of abuse on multivariate emotional and behavioral risk is assessed. A total of 3998 students (69%) in a rural midwestern community in grades 7 to 12 participated in the study. Almost 20% of the students reported some form of physical and/or sexual abuse, with more girls than boys reporting sexual abuse (chi 2 = 48.5, P less than .001). Some problem behaviors (alcohol use) and emotions (trouble sleeping, difficulty with anger) were common among all adolescents and some were strongly associated with a history of abuse (especially, considering or attempting suicide, running away, laxative use, and vomiting to lose weight). Higher emotional and behavioral risk scores among abused students were confirmed. The effects of physical and sexual abuse on risk scores were independent and additive; no interaction was observed. An interaction of gender and sexual abuse on problem behavior was observed, with problem behavior being significantly greater among sexually abused boys. The results confirm increased risk of problem behaviors and negative feelings among abused adolescents when compared with nonabused peers, and better define influences of gender and abuse type on emotional and behavioral risks. PMID- 2251028 TI - High-fat semielemental diet in the treatment of protracted diarrhea of infancy. AB - The capacity for greater fat absorption relative to carbohydrate absorption in protracted diarrhea of infancy was studied in a developed and a developing country (Buffalo, NY, and Bangkok, Thailand). Fifty patients with protracted diarrhea in the first year of life (defined as liquid stools of more than 20 mL/kg per day with more than a 14-day duration) were randomly assigned to receive either a standard semielemental diet (Pregestimil) or a high-fat semielemental diet that contained 40% more fat. The increased fat was largely in the form of medium-chain triglycerides, with the new diet providing 60% of the fat as medium chain triglycerides compared with 40% in the standard diet. Tolerance to both diets was good in both studies. Both groups showed adequate weight gain and an improvement in anthropometric and biochemical parameters. The patients receiving the high-fat diet showed no initial weight loss, however, and their weight gain was initiated earlier. Cumulative weight gain was also higher in the group receiving the high-fat semielemental diet. Fecal fat analyses were performed after 1 week of therapy. There was no difference observed in the coefficient of fat absorption between the groups receiving the two formulas, indicating that infants with protracted diarrhea may be able to tolerate a higher fat intake than is normally provided. As carbohydrate intolerance is known to be a complicating factor when using semielemental enteral feeds for infants with protracted diarrhea, a higher-fat semielemental diet may be the most appropriate way to provide adequate caloric intake. PMID- 2251029 TI - Amino acid concentrations in plasma and urine in very low birth weight infants fed protein-unenriched or human milk protein-enriched human milk. AB - Preprandial plasma and urine amino acid concentrations were measured in 28 growing, very low birth weight, appropriate-for-gestational-age infants randomly assigned to either protein-unenriched (n = 14) or human milk protein-enriched (n = 14) human milk. The two groups of infants had similar birth weights (900 to 1500 g) and gestational ages (26 to 32 weeks). The study was initiated at a mean age of 19 days when the infants tolerated full feeding volumes and lasted for a mean time of 28 days. Mean protein intake values were 2.1 +/- 0.3 and 3.6 +/- 0.3 g/kg per day (mean +/- SD) and weight gain values were 26.6 +/- 7.4 and 35.1 +/- 3.6 g/day in the protein-unenriched and the protein-enriched groups of infants, respectively. Human milk protein enrichment resulted in significantly increased concentrations of all plasma amino acids except serine, taurine, and histidine. Most urine amino acid concentrations correlated with protein intake and with the plasma concentrations, suggesting that the effects of protein quality and quantity can be evaluated by measuring urinary amino acid concentrations alone, thereby making such studies less invasive. Infants fed protein-unenriched human milk had growth rates below the estimated intrauterine rate as well as low plasma and urine amino acid concentrations, indicating suboptimal protein intake levels. When the plasma concentrations of the essential amino acids in the protein enriched infants from the present study were compared with concentrations found in the literature in fetal and umbilical cord plasma, both were found to be much higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251030 TI - Eleven plasma proteins as indicators of protein nutritional status in very low birth weight infants. AB - Concentrations of 11 plasma proteins were measured in 28 healthy, growing, very low birth weight, appropriate-for-gestational-age infants fed varying levels of human milk protein intake (range 1.7 to 3.9 g/kg per day). Significant positive correlations were found between mean protein intake and concentrations of 7 of the plasma proteins studied (transthyretin, retinol-binding protein, and transferrin: P less than .001; vitamin D-binding protein and apolipoprotein B: P less than .01; albumin and apolipoprotein A I: P less than .05). A weak negative correlation with mean protein intake was seen for the plasma level of orosomucoid, whereas no significant correlations were found for the plasma concentrations of fibronectin and alpha 1-antichymotrypsin. Protein intake, not energy intake, constituted the main contribution to the changes in the concentrations of transthyretin, retinol-binding protein, and transferrin. The levels of plasma transthyretin and transferrin were also strongly correlated with weight and length growth of the infants during the study as well as with other indicators of protein nutritional status such as preprandial concentrations of plasma amino acids and serum and urine urea. These data indicate that of the 11 plasma proteins studied, transthyretin, transferrin, and retinol-binding protein are the most suitable to evaluate protein nutritional status in very low birth weight infants. PMID- 2251031 TI - Neonatal ethics: development of a consultative group. AB - Experience of a neonatal ethics advisory group in a tertiary care setting was reviewed to identify which aspects of the experience have been most valuable in the development of a consultative group. Consultations were requested for 31 patients seen from August 1984 through December 1988. Review of these patients indicated that 21 of 31 infants were born after full-term gestations, 11 of 31 infants were seen beyond the neonatal period, and some type of congenital anomaly was the principal diagnosis for 64.7% of the patients. The reasons for seeking consultation primarily involved decisions regarding withdrawal or withholding of treatment. For 22 of the 31 patients, the consensus of the group supported the decision of the health care team. In the remaining consultations, the recommendation of the group was that more information and/or communication was needed. In the analysis of the neonatal ethics advisory group's experience with consultations the characteristics of neonatal patients were identified and the value of having a forum for discussing the difficult ethical issues facing members of the health care team were validated. PMID- 2251032 TI - Quantifying language development from birth to 3 years using the Early Language Milestone Scale. AB - A point-scoring technique for the Early Language Milestone Scale is described. Normative data based on the original 1982 cross-sectional sample and validation data based on a separate longitudinal sample are presented. Mean Early Language Milestone Scale point scores, standard deviations, and percentile equivalents for raw point scores are presented for all ages from birth to 36 months. Correlations between point scores on the Early Language Milestone Scale and scores on other standardized developmental tests such as the Stanford-Binet Intelligence Scale, the Peabody Picture Vocabulary Test, and the Illinois Test of Psycholinguistic Abilities are presented. The clinical and research advantages of this point scoring technique are presented and compared with the original pass/fail scoring method. PMID- 2251033 TI - Delayed detection of coarctation in infancy: implications for timing of newborn follow-up. AB - During a recent 5-year period, 74 patients younger than 6 months of age were diagnosed with coarctation of the aorta. Coarctation was correctly diagnosed in only 22% of patients prior to referral despite readily apparent femoral pulse abnormalities in 86%. Infants whose symptoms were detected between 5 and 14 days of age were significantly more ill than infants outside this age range and had a high mortality rate (25%). The number of associated cardiac defects was not related to the severity of clinical illness in this group, suggesting that closure of the ductus arteriosus is the primary determinate of disease severity. Observations in two patients suggested that a detectable pulse discrepancy occurs between 3 and 5 days postnatally. Upper extremity hypertension was found commonly in infants after 5 days of age despite the presence of congestive heart failure. Earlier detection of coarctation in the newborn requires a diligent cardiovascular and peripheral pulse examination between 3 and 7 days of life, upper extremity and lower extremity blood pressure measurement, and a high index of suspicion. PMID- 2251034 TI - Response to diet and cholestyramine in a patient with sitosterolemia. AB - In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis. PMID- 2251035 TI - After teen suicide: issues for pediatricians who are asked to consult to schools. AB - Every suicide is a unique tragedy. This article has attempted to provide a framework for understanding suicide as it impacts on the school community. Given this background, we have listed 10 frequent dilemmas faced by pediatricians (and others) who consult to schools. The central themes of the approach offered are to avoid inadvertently glorifying suicide, target high-risk groups for interventions, and consider suicide prevention as part of the broad, ongoing task of providing a caring environment for adolescents in which the collaboration of the school community is essential. PMID- 2251036 TI - Congenital abnormalities of the lymphatic system: a new clinical classification. AB - The numerous clinical presentations of congenital abnormalities of the lymphatic system in children and the confusing terminology used to describe their pathologic diagnoses impede the physician's understanding of the condition. The clinical classification based on the actual symptoms of the congenital problems we have presented here should help the physician identify the specific abnormality and a potential treatment. Future research should concentrate on the specific causes and the treatment of these congenital abnormalities. PMID- 2251037 TI - Duplicate publication and related problems. PMID- 2251038 TI - American Academy of Pediatrics Committee on School Health: Guidelines for urgent care in school. PMID- 2251039 TI - [Pediatric polyclinic complex]. PMID- 2251040 TI - [Activation of the complement system and its components in healthy children aged 4 to 15 years]. PMID- 2251041 TI - [Intestinal motility in relation to the type of the autonomic nervous system in practically healthy children 5 and 6 years of age]. PMID- 2251042 TI - [Clinico-psychological correlations in children with non-infectious gastrointestinal pathology]. PMID- 2251043 TI - [Immunologic characteristics of different types of glomerulo- nephritis]. PMID- 2251044 TI - [Fecal intestinal microflora in children with pyelonephritis]. PMID- 2251045 TI - [Plasma malondialdehyde and lactate levels in children and adolescents with diabetes mellitus]. PMID- 2251046 TI - [Histocompatibility antigens in children with acute lymphoblastic leukemia]. PMID- 2251047 TI - [Duodenogastric reflux and functional state of the stomach and duodenum]. AB - As many as 91 children with different gastroenterological diseases were examined. 57.8% of the children manifested the duodenogastric reflux. Acid-forming function of the stomach appeared normal or elevated. Electrogastrography showed the predominance of the hyperkinetic and normokinetic curve types. Manometry of the stomach and duodenum often demonstrated duodenal hypertension with a reflux of the duodenal contents to the stomach. The incidence of the duodenogastric reflux was not dependent on the patients' age, sex or disease standing. Alterations in the gastric and duodenal mucosa may be both the cause and consequence of the gastroduodenal reflux. PMID- 2251049 TI - [Adaptive potential of the secretory system of the stomach in different phases of peptic ulcer in children]. AB - A conjugated shift in the levels of total acidity and lysozyme in the fasting portion of gastric juice within the system of coordinates enables the diagnosis of the stages of the adaptation syndrome and the respective levels of the functioning of the secretory gastric apparatus, which in turn specify differentiation of peptic ulcer phases. The levels of total acidity and lysozyme, the indirect parameter of the level of the secretory apparatus functioning have been measured in accordance with gastric juice fractions in healthy children. PMID- 2251048 TI - [Clinical significance of the changes in glucose-6-phosphate dehydrogenase activity in blood cells of children with acute intestinal infections]. PMID- 2251050 TI - [Activity of acetylation processes and the indicators of the lipid spectrum of blood in children with combined gastro-duodeno-biliary pathology]. AB - As many as 110 children with chronic gastroenterological diseases were examined for coenzymic acetylation in the liver and for the blood lipid spectrum. Considerable disorders in the activity of the acetylation processes in the liver and unbalance in the blood lipid spectrum have been revealed. A complex of vitamins exerting a protective action on the system of coenzymic acetylation in the body have been tried. PMID- 2251052 TI - [Ultrasonography in differential diagnosis of recurrent abdominal pain in children]. AB - The authors relate the data obtained during echographic examination of 863 children suffering from gastric pains. Proceeding from the clinical and laboratory data the early topical diagnosis of the causes of the painful syndrome was impeded. Use was made of ultrasonography of the gallbladder along with its function estimation, of the intra- and extrahepatic bile ducts as well as of the liver and pancreas. A study was made of correlations between the echographic signs of the microscopic and biochemical indicators of the bile and the status of the duodenal mucosa (according to esophagogastroduodenoscopy). The data obtained demonstrate great potentialities of echography in differential diagnosis of gastric pains in children. PMID- 2251051 TI - [Criteria of severity of the pathological process in children with celiac disease]. AB - Assessment of the clinico-anamnestic and morphofunctional parameters in children with celiac disease made it possible to define criteria for the acuity of the pathological process, enabling the diagnosis of the disease phase. The data obtained as a result of morphometric examination of the biopsy material withdrawn from the small intestinal mucosa turned out to be of paramount importance. PMID- 2251053 TI - [Hypoparathyroidism in children]. PMID- 2251054 TI - [Possibilities of detection of pericardial effusion in children]. PMID- 2251055 TI - [Diagnostic sensitization with food antigens for predicting dietetic correction of celiac disease in children]. PMID- 2251056 TI - [Current problems of maternal and child care]. PMID- 2251057 TI - [Individualized euphylline therapy of children with refractory recurrent bronchial asthma controlled by therapeutic monitoring]. PMID- 2251058 TI - [Effectiveness of the treatment of children with hereditary pathology in a specialized clinic]. PMID- 2251059 TI - [Life style and children's health]. PMID- 2251060 TI - [The endocrine system in newborn infants]. PMID- 2251061 TI - [Reye's syndrome in a 15-month-old child]. PMID- 2251062 TI - [Acute renal failure in a generalized form of pseudotuberculosis in children]. PMID- 2251063 TI - [2 cases of toxocariasis in children]. PMID- 2251064 TI - [Experience with the prevention of enterobiasis in children from preschool institutions of the Zhitomir district]. PMID- 2251065 TI - [Experience with early excision of the umbilical cord stump in newborn infants with subsequent use of "lifuzol"]. PMID- 2251066 TI - [Rational tactics in the treatment of acute stenosing laryngo- tracheitis in children]. PMID- 2251067 TI - [Insect-induced allergy in children]. PMID- 2251068 TI - [Nephropathies associated with disorders of oxalic acid metabolism]. PMID- 2251069 TI - [Current principles of chemotherapy of nonspecific ulcerative colitis in children]. PMID- 2251070 TI - Somatization tendencies and ability to detect internal body cues. AB - 39 subjects performed a task in which they were required to detect the presence of a resistive load during the inhalation phase of breathing. Subjects were also measured on somatization tendencies, using the SCL-90-R test. A signal-detection analysis indicated an inverse relationship between ability to detect the resistive load during breathing and somatization score. Results are discussed relative to possible ramifications for somatoform disorders. PMID- 2251071 TI - Reaction time and index of difficulty in target-striking tasks with changes in direction. AB - Reaction time (RT) for two three-segment target-striking responses involving changes in direction of movement was studied as a function of differences in their additive index . . . index of difficulty (A-ID). In one condition the A-ID was 9.96 and in the other, 6.76. For 16 right-handed university students, mean RT was significantly faster for the condition in which the index was 6.76. Movement times were consistent with Fitts' Law. The data support Sidaway, Christina, and Shea's 1988 prediction that for target-striking movements with changes of direction, RT is a function of the cumulative series of movement constraints. PMID- 2251072 TI - Psychology of the scientist: LXIII. Perceiving scattergrams: is visual line fitting related to estimation of the correlation coefficient? AB - Visual line fitting and direct estimation of the correlation coefficient were carried out by 50 subjects using computer-generated scattergrams as stimuli. In visual line fitting, slopes of visual lines were generally greater than the corresponding regression slopes, in agreement with the hypothesis that visual lines are placed so as to bisect the cloud of displayed points at the cloud's major axis rather than to approximate a regression line. Subjects tended to underestimate the correlation coefficient, scaling their judgments of linear structure somewhat more as if they were judging the coefficient of determination. With the actual degree of linear structure partialed out, there were no strong relationships between measures of visual line fitting and measures of estimation. While both of these tasks offer quickly-obtained correlates of linear structure in scattergrams, users should be aware of their biases. We suggest that visual lines do not approximate regression lines very well and estimates of correlation do not approximate the correlation coefficient very well, because the perceptual processes involved perform operations other than regression and correlation. In the present data, these operations appeared to be independent of each other. PMID- 2251073 TI - Automaticity in spelling competence. AB - Two studies examined the speed with which good spellers and poor spellers spell easy and difficult words. At both the elementary school (Grades 3 and 4) and undergraduate levels, good spellers spelled words more quickly than poor spellers. This difference appeared even for very easy words that all subjects could spell. Implications for the importance of automaticity in spelling competence are discussed. PMID- 2251074 TI - Development of internal body image from childhood to early adolescence. AB - The study aimed at providing a psychogenetic characterization of the developmental patterns through which the graphic representations of the inside of the body progress, and at testing the developmental hypothesis of a progressive integration of genital parts into the internal body image. The drawings of the inside of the body by 360 children of both sexes and of age 5 to 10 yr., and by 213 early adolescents, boys and girls of ages 11 to 14 yr., were analyzed on the basis of a series of qualitative and quantitative criteria. The relationship between age and type of drawing corresponds to expectations in children and appears less linear for early adolescents. Further, data support the developmental process of integration of genitals into the body image and show differential aspects in boys and girls. PMID- 2251075 TI - Preliminary analysis of effects of "normal" aging on different memory processes and abilities. AB - Visual recognition-memory span, name-face association, and verbal memory with selective reminding were tested in two groups of 24 normal healthy volunteers (above and below age 50 yr.). The preliminary study suggests differential effects of aging on specific memory components and warrants careful exploration. PMID- 2251076 TI - Judgments about suicide: morality versus rationality and personal versus impersonal. PMID- 2251077 TI - Coping and job performance. AB - An organizational field study comprising 42 subjects examined the relationship between growth-oriented coping and subsequent job performance. Growth orientation was measured using the 7-item growth scale obtained from the Lazarus Ways of Coping Checklist. The hypothesized relationship between growth orientation and job performance was confirmed. Individuals obtaining high evaluations of managerial performance emphasized growth-oriented strategies in their behaviors. Further research directions are introduced. PMID- 2251078 TI - Drawings of the President: 1980 and 1984. AB - In Study 1, 77 children in Grades 3 and 6 were asked to draw pictures of the three major Presidential candidates (John Anderson, Jimmy Carter, and Ronald Reagan) at 2-wk. intervals beginning October 1, 1980 (about five weeks before Election Day) and ending November 12, 1980 (about one week after Election Day). It was hypothesized that the pictures would increase in size until Election Day and decrease thereafter. Drawings of Carter and Reagan decreased after Election Day, while those of Anderson began decreasing three weeks before the election. In Study 2, 81 children in Grades 4 and 5 drew pictures of Ronald Reagan and Walter Mondale at 2-wk. intervals during the 1984 Presidential campaign. Drawings of Reagan decreased in size after Election Day but not those of Mondale. PMID- 2251079 TI - Sudden infant death syndrome and possible relation to vestibular function. AB - Some infants seem to be born with a degree of respiratory centre immaturity which in combination with other problems such as illness, head colds, exposure to cold, air or smoke, may result in cessation of breathing. Vestibular stimulation by rocking has been shown to be beneficial for premature babies in reducing apnea. There also appear to be other benefits, resulting in more rapid maturation of the nerve cells of the cerebellum which is still developing during the first six months of life. The suggestion is made that crib deaths may be reduced by the use of automatically rocking cribs, particularly during the night when most deaths occur. PMID- 2251080 TI - Effects of age and brightness contrast on perception of the Wundt-Hering illusion. AB - Susceptibility to the Wundt-Hering illusion was studied as a function of age and contrast. Preschoolers, third-graders and college students were shown light-grey, medium-grey, and black Wundt-Hering figures on white ground. Pre-schoolers were most susceptible to the illusion, differing from third graders in the medium and high contrast conditions and from college students in all contrast conditions. Low contrast figures resulted in significantly less distortion than did high contrast figures for the preschoolers. The significant interaction of age and contrast effects highlights the importance of a developmental approach to the study of illusions. PMID- 2251081 TI - Effects of target-background luminance ratios upon the autokinetic illusion. AB - This study investigated effects of the target-background luminance ratios upon the autokinetic illusion, with special emphasis on manipulation of the background intensity. Exp. 1, in which the effects of four levels of target luminance were examined against the completely dark background, showed that the target luminance did not affect the illusion as long as the target was small enough in size (0.17 degrees in visual angle). This result confirmed the suggestion by Edwards in 1954. In Exp. II effects of the target-background luminance ratios were examined by varying the luminance of target and background independently. Dominant illusory patterns at the luminance ratio 1 were "pendulum-like" and "bobbing"; these differed from those at higher ratios ("winding"). On the other hand, latency and duration were not affected by the ratios. These findings suggest that the movement pattern is effective in specifying the autokinetic illusion, if it is appropriately categorized and represented. PMID- 2251082 TI - Area perception in simple geometrical figures. AB - The results of experiments on visual perception of area of circles and squares are reported. Pairs of geometrical figures were presented simultaneously on an oscilloscope screen. While one of them was fixed, the other one was controlled by an experimental subject. The task of the subject was to match the area of the variable figure to the area of the fixed one. The obtained data show underestimation of the area of circle when compared with square. A mathematical model designed to explain this phenomenon is proposed here. The image function defined as a low-pass filtered (blurred) version of the figure is employed for this purpose. Then, instead of the position of the image function maxima, the position of a threshold value is used for area computation. PMID- 2251083 TI - Light sensitivity in peripheral retinal fields of dyslexic and proficient readers. AB - This present study furthers research on perceptual differences between dyslexics and normal readers which is contrary to the current linguistic approaches to this problem. Specifically, thresholds of light intensity for small retinal areas were examined. As hypothesized, the peripheral retinas of proficient readers evidenced lower thresholds than the peripheral retinas of dyslexic readers. These results are consistent with Grosser and Spafford's previous research which showed that dyslexics were better able to detect colors with their peripheral retinas than proficient readers. This research lends support to the premise that dyslexics' retinas have unusually high cone density in the periphery. Additional research is warranted to improve both diagnosis and treatment of dyslexia. PMID- 2251084 TI - Hemispheric performance in detecting prosody: a competitive dichotic listening task. AB - Ross's 1981 model of right-hemisphere processing of affective speech components was investigated within the dichotic paradigm. A spoken sentence constant in semantic content but varying among mad, sad, and glad emotional tones was presented to 45 male and 45 female college students. Duration of stimuli was controlled by adjusting digital sound samples to a uniform length. No effect of sex emerged, but the hypothesized ear advantage was found: more correct identifications were made with the left ear than with the right. A main effect of prosody was also observed, with significantly poorer performance in identifying the sad tone; in addition, sad condition scores for the right ear were more greatly depressed than those for the left ear, resulting in a significant interaction of ear and prosody. PMID- 2251085 TI - Stereotypical beliefs about appearance: implications for retailing and consumer issues. AB - This research was designed to identify current stereotypical beliefs about obese men and women, assess subjects' desire to work with individuals described as "normal" weight as opposed to obese, examine subjects' perceptions of their own body size, inquire about subjects' personal desire to gain and lose weight, and identify subjects' diet and consumption behavior. The data indicate sex differences in subjects' perceptions of bodily appearance, desire to work with obese people, perceptions of their own weight, desire to lose rather than gain weight, and consumption and diet behavior. PMID- 2251086 TI - Hemisphericity style, sex, and torque: an exploratory study. AB - A sample of 139 male and 218 female college students were given the Preference Questionnaire and a torque test to assess (a) whether subjects who prefer a left hemisphericity style would show a higher incidence of torque than those who prefer a right hemisphericity style and (b) whether men would yield a higher incidence of torque than women. The first hypothesis received limited support. Men with a left hemisphericity style yielded a higher incidence of torque than men with a right style, however, the difference was only marginally significant. PMID- 2251087 TI - Multivariate analyses of cognitive and cognitive style variables based on hemisphere specialization theory predictive of success in a college developmental studies program. AB - Right and left cerebral hemisphere and limbic scores derived from the Herrmann Brain Dominance Profile, Scholastic Aptitude Test Verbal and Mathematics scores, and High School Grade Point Average were correlated with grades in college developmental courses in reading, English, and mathematics for 146 students. Pearson correlations ranged from -.27 to .42. Multiple correlations with seven predictors ranged from .45 to .55, and from .14 to .37 for the profile scores alone. Discriminant analyses yielded hit-rates (predictive of classification of success and failure/actual classification) of 69%/72% in Reading, 76%/75% in English, and 66%/71% in Mathematics. PMID- 2251088 TI - Scaling of response scale adverbs among black-American adults. AB - Although some attention has been given to the scale characteristics of modifying adverbs in Likert scales, the existing work has been concerned primarily with majority group members. Toward the goal of identifying valid labels for use on Likert scales with black-American respondents, 105 black-American adults scaled each of 27 adverbs (e.g., very, most) on four different adjectives (e.g., important). Four criteria for a set of ideal adverbs were identified for univalent scales. No set of four adverbs, however, met the criteria. Differences in the mean ratings of eight of the adverbs were found by sex group and across the four adjectives modified. The adverbs were not scored at the extremes of the continuum, despite our asking the respondents to rate the adverbs used to define the end points of the continuum. High variances were found across all adverbs. Further research must address the respondents' perceptual frame in the use of such scales. PMID- 2251089 TI - Simulation in hypnosis research: the "hidden" role of attribution of meaning. AB - The role played by attribution of meaning in research involving simulation is examined. Acknowledgement of this role, lacking to date, queries the traditional use of simulation but also opens up interesting research questions. PMID- 2251090 TI - Research on the clinical usefulness of the Rorschach: 1. The diagnosis of schizophrenia. AB - Research on the use of the Rorschach in the diagnosis of schizophrenia is reviewed. The analysis of this research (from that done by Rorschach to the most recent) indicates that schizophrenics do not respond in any unique fashion to any particular determinant or any particular card. The research also indicates that the computation of percentages and ratios, no matter how complex, does not facilitate the identification of a schizophrenic process. What the research does demonstrate is that schizophrenia, in its overt as well as latent and borderline forms, is detectable on the Rorschach through an analysis of the patient's thinking. The thinking of the schizophrenic reveals highly personal, illogical, and bizarre associations to the blots. This analysis of thinking is not accomplished through assessment of the formal properties of the blots, e.g., the analysis of response to color, movement, shading, the color-to-movement ratio, or form level (low form level proves to be a function of psychoticism, not schizophrenia, per se) but more in terms of the phenomenology of the responses. PMID- 2251091 TI - Behavior at 10 and 13 years of age for children with low birth weight. AB - This study was based on data from a longitudinal research program. The cohort consisted of 874 normal children in an entire school grade in a Swedish community. The aim of the study was to investigate the relation between birth weight and behavior at school, for all children and for each sex separately. The results identified specific aspects of behaviour disorder significantly related to low birth weight (LBW) for children at the age of 10 but not at the age of 13. When the sexes were separated, there were no relations between birth weight and deviant behaviour for boys of low birth weight as compared to boys of normal birth weight, while girls of low birth weight showed specific behavioural disorders at age 10 as compared to girls of normal birth weight. For girls reared in families of low parental socioeconomic status, aggressiveness and motor restlessness at age 10 but not at age 13 was also present. Further analyses showed that girls born small-for-gestational age showed lack of school motivation and concentration difficulties both at age 10 and age 13. PMID- 2251092 TI - Effects of variations in force on fractionated reaction time in simple and choice conditions. AB - The present study examined the effects of force output on fractionated reaction time under simple and choice conditions. 20 subjects were required to react and produce a designated force as soon as possible after a visual stimulus. Five different levels of force were 10, 30, 50, 70, and 90% of the maximum grip strength of the subjects. Analysis showed that reaction time (RT) changed as a function of force in both conditions, with the longest RT occurring at the 70% condition. The same pattern was also evident for premotor time. These findings suggest that the changes in RT with increases in force are mediated predominantly by central rather than peripheral processes. PMID- 2251093 TI - Relationships among age, sex, and lateral dominance for 3- to 6-year-old children performing unilateral stance. AB - To assess influence of age, sex, and lateral dominance on children's unilateral stance, from 6 Houston area preschools and day-care centers, 121 subjects were randomly selected and judged by teachers as normal 3- to 6-yr-old children. The children were tested for eye, hand, and foot preference and were then classified on over-all dominance. Maximal duration of unilateral stance, or up to 60 sec., was tested on each foot. Means over age groups show progressive increase in duration of unilateral stance with increasing age. No sex differences were found. A stepwise multiple correlation-regression showed stance on the nondominant foot and age as the only significant variables in stance on the dominant foot. Clinically, this study can help in evaluating children for neurodevelopmental disorders. PMID- 2251094 TI - The multiplicity of dreams: cognitive-affective correlates of lucid, archetypal, and nightmare dreaming. AB - This preliminary research is the first to compare lucid, nightmare, and archetypal-mythological dreams on dimensions important in previous research on each. A first study of 100 subjects showed all three forms significantly correlated with each other and with estimates of dream recall. In a second study, 41 subjects were selected from the above on the basis of relative specialization in each dream form, with a control group equally high on dream recall. Here, the lucid and archetypal dreamers tended to separate themselves from nightmare sufferers on the basis of high imaginativeness, proclivity to waking mystical experience, spatial/analytic skills, and physical balance. It appears that the intensification of dreaming is expressed positively or negatively, depending on variations in these cognitive dimensions. PMID- 2251095 TI - The early motor profile: correlation with the Bruininks-Oseretsky Test of Motor Proficiency. AB - A correlational study of the Bruininks-Oseretsky Test of Motor Proficiency and the Early Motor Profile with 109 kindergarten children showed a significant relation between these two measures of motor abilities. These results support use of the latter profile as a measure of motor development in preschool age children. PMID- 2251096 TI - Effects of an emotional negative stimulus on the cardiac, electrogastrographic, and respiratory responses. AB - The experiment investigated the effects of two film sequences, one neutral and the other emotional, on the cardiac (ECG), electrogastrographic (EGG) and respiratory activities of 24 healthy students during digestion. The physiological activity was recorded before and during the projection of each film sequence. 12 subjects were shown a neutral film sequence and 12 an emotional film sequence. At the end of each viewing period, each subject completed a self-rating questionnaire on the emotional experience. Analysis indicated, with respect to the previewing (baseline) values, an increase in cardiac and respiratory rates and a decrease in electrogastrographic rates during the viewing of the film sequences. Changes in the EGG rate (baseline to viewing) were negatively correlated with the changes in ECG and respiratory rates, whereas the changes in these latter two were positively correlated. In comparing the effects of the neutral and emotional scenes the only significant result was the heart-rate increase in subjects watching the emotional sequence. Also, the self-rating of emotional experience varied with the emotional value of the sequence. PMID- 2251097 TI - Influence of play on creative thinking. AB - The immediate influence of flexible and highly structured play on the creative thinking of 184 fourth-grade boys and girls was investigated. Following either flexible or highly structured art, drama, and playground activities, children's performances on the Torrance Tests of Creative Thinking were evaluated. Children who participated in flexible play experiences showed significantly greater creative thinking than children participating in the highly structured play experiences. No significant differences were found between boys and girls related to effects of flexible and structured play on creative thinking. Implications for curriculum are explored. PMID- 2251098 TI - Wire-bending test as a predictor of preclinical performance by dental students. AB - Traditional Dental Aptitude Test and academic grade point average have been shown to be poor predictors of clinical performance by dental students. To refine predictors of psychomotor skills, a wire-bending test was given to 105 freshmen at the beginning of their dental education. Grades from seven restorative preclinical courses in their freshman and sophomore years were compared to scores on wire bending and the three traditional predictors: GPA, academic aptitude, and perceptual aptitude scores. Wire-bending scores correlated significantly with six out of seven preclinical restorative courses. The predictive power for preclinical performance was doubled when wire bending was added to traditional predictors in stepwise multiple regression analysis. Wire-bending scores identified students of low performance. These preliminary results suggest that the wire-bending test shows some potential as a screening test for identifying students who may hae psychomotor difficulties, early in their dental education. PMID- 2251099 TI - Effects of age and sex on reciprocal tapping performance. AB - Using a reciprocal tapping task (Fitts's task), the speed and accuracy of small amplitude motor movements of the hand were measured for 62 men and 84 women, 20 to 89 yr. of age. Men and women in their 20s and 30s performed similarly, although men in their 20s displayed a tendency to trade accuracy in favor of speed. Movement time increased noticeably for both men and women beginning with the 40s decade and continued to increase through the 80s decade. Error rates were lower for women than men and were relatively uniform for both men and women across all age decades past 30 yr. Older subjects of both sexes appeared to sacrifice speed (slowed down) to maintain accuracy on the task. The slope of the linear regression relating movement time to task difficulty was steeper for men than for women and increased more for men than women with advancing age, indicating that older men slowed down relatively more than older women on more difficult tasks. PMID- 2251100 TI - Concurrent validity of the motor domain of the Vineland Adaptive Behavior Scales. AB - The concurrent validity of the motor domain from the Vineland Adaptive Behavior Scales was estimated using scores from the Peabody Developmental Motor Scales as criteria. A moderately high correlation between the measures was obtained. Implications, particularly for preschool children, were discussed. PMID- 2251102 TI - [Changing one's lifestyle]. PMID- 2251101 TI - Effects of alcohol and white noise on recall of relevant and irrelevant task components. AB - This study examined the effects of arousal, induced by alcohol and white noise, on the free recall of intentionally learned words and incidentally learned word locations, in the presence or absence of word-order cues. The Activation Deactivation Adjective Check List, a self-report measure of arousal showed that noise affected the tension dimension of arousal, whereas the moderate alcohol dose primarily affected the energy dimension of arousal. That the low dose exerted an arousing effect was evidenced by an increase in tension but only when combined with noise. When word-order was randomized over trials, noise improved word-recall and counteracted the deleterious effect of the moderate alcohol dose. When order remained fixed, however, the moderate dose impaired recall, and at that dose recall was worse under noise. Location-recall was impaired by the moderate dose, and it was superior when word-order remained fixed. It was concluded that recall was influenced by arousal mechanisms and that perceived task demand and consequent effort were possible factors contributing to the obtained effects. PMID- 2251103 TI - [Diet treatment in clinical practice. Advice on diet--more than a knowledge of dietetics]. AB - Eating habits are deeply rooted and founded early in life. The need to change one's eating habits in order to treat a certain disease or a metabolic disorder may seem to impose a well nigh impossible task. It is therefore extremely important that the dietitian adjust the recommendations to each individual's needs, wishes and circumstances. The article translates nutritional objectives into practical advice. The desired dietary composition is essentially the same for the foods which are recommended for the treatment of diabetes, hyperlipoproteinemia and hypertension. PMID- 2251104 TI - [The effect of diet on the treatment of malignant diseases]. AB - The importance of dietary factors for the incidence of cancer has been discussed to an increasing extent in recent years while less attention has been devoted to the effect of food on the treatment of an established oncological disease. Carcinoma per se gives rise to reduced food consumption, and different treatments such as surgery, chemotherapy and radiotherapy contribute further to disturbances of nutrition. This article summarises current knowledge of the potential significance of diet and its various components for optimal cancer therapy. There may well be profit to be gained as regards anti-cancer therapy and generally supportive measures. PMID- 2251105 TI - [The role of serotonin in normal appetite regulation and in the pathogenesis of anorexia/bulimia]. AB - Evidence accumulated over the past two decades indicates the existence of several neurochemical systems that influence feeding behavior. The central region regulating appetite is thought to be in the hypothalamus, where different monoaminergic systems are localized. It has been suggested that altered function in these systems is taking part in the pathogenesis of anorexia and bulimia nervosa. According to these theoretical principles and to the development of specific monoaminergic and anti-monoaminergic drugs, the pharmacological treatment of eating disorders can become more successful in the future. This article discusses the role of serotonin in appetite regulation and presents new evidence that a dysfunction in hypothalamic serotonergic pathways can be an important part of the pathogenesis of anorexia and bulimia nervosa. PMID- 2251106 TI - [Crohn's disease and its sometimes many disguises]. AB - The textbook descriptions of Morbus Crohn demonstrate the so-called classic pathology, viz. pains in the ileo-caecal region, a tendency to diarrhoea, a distinct swelling at MacBurney's point, and a certain loss of weight. But the course of the disease is sometimes atypical, which may involve a long delay in the diagnosis. The disease may be seen in all age groups and seems to increase. PMID- 2251107 TI - [Helicobacter pylori]. AB - Ever since 1983 when Marshall & Warren succeeded in cultivating Helicobacter pylori (HP) (previously known as Campylobacter pylori) a high incidence thereof has been demonstrated in patients with ulcers and non-ulcerous dyspepsia. Helicobacter pylori is easily diagnosed via microscopy, cultivation and serological tests. The bacterium may be treated with antibiotics or the ulcer drug bismuth subcitrate (De-Nol). The pathogenetic role of HP is not clear. Some studies have shown a lower recurrence rate of duodenal ulcers after treatment addressed to Helicobacter pylori with the ulcer drug De-Nol, which suggests that HP plays a role in the onset of recurrence in cases of ulcus duodeni. PMID- 2251108 TI - [Symphysis-fundus measurements in Scandinavia]. AB - Since the late 1970s symphysis-fundus measurements have been used in the Nordic countries to predict fetal growth deviation. Via a questionnaire, sent to Nordic university hospitals representative of health care areas, existing practices have been investigated. Symphysis-fundus measurements are almost invariably obtained and plotted onto nomograms as part of routine antenatal care. Five normal curves are in use showing some variation, but there are considerable differences in the selection of material and in the statistical treatment of the data. Revision of some of these curves may be required. PMID- 2251109 TI - [Statistical analysis of 2 x 2 tables: II. Cohort and case-control studies]. AB - The two most frequent forms of epidemiological investigation are the cohort study and the case control study, which was reviewed in a previous article. This article examines the most commonly used methods of statistical analysis of these studies applied to the 2 x 2 table. PMID- 2251110 TI - [Scientific theory and drug abuse research]. AB - Scientific medicine has for years been faced with the classical philosophical dilemma between ontological realism and epistemological empiricism. The impact of this dilemma is especially important in scientific psychiatry and, not least, in the study of substance use disorders. Much controversy exists concerning the question of what psychiatric diseases "really are" and how disease should be separated from non-disease. The anti-psychiatric movement claimed that the disease model in psychiatry should be totally abandoned, and the impact of this movement on our daily thinking may have been greater than we have generally recognized. As for the substance use disorders there is no doubt that the disease model is generally considered no use. But giving up the disease model--or one of the disease models--has serious consequences for the scientific study of these disorders. The interpretation of data from eg a long-term follow-up study of substance users is impossible except in a disease-model frame-of-reference. So is any search for causes or search for effects of a certain treatment. Usually an explicit discussion of the philosophical frame-of-reference in such studies is not given with the consequence that scientific discussions of substance use or substance use disorders are often waste of time. PMID- 2251111 TI - High-frequency transformation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of Schizosaccharomyces pombe. AB - We describe a highly efficient alkali cation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of fission yeast Schizosaccharomyces pombe mutants. cDNA libraries constructed with the pcD or pcD2 vector are transduced into yeast by cotransfection with a linearized vector, which allows an enhanced homologous recombination between the yeast vector and the library plasmid leading to the efficient formation of concatemers containing pcD molecules. The transformation frequencies obtained by the method are 10(6) colonies per 10(8) cells transfected with 2 micrograms of library and 1 microgram of vector, 50-60% of which contain pcD molecules. The high-efficiency alkali cation method circumvents many of the shortcomings of the spheroplast method generally used for Schiz. pombe transfection. The vectors are maximized for the efficiency of library transduction and minimized for the rearrangements of pcD molecules during propagation in yeast. This system allows rapid screening of multi-million cDNA clone libraries for rare cDNAs in a routine scale of experiments. Using this system, various mammalian cDNAs that are extremely difficult, time-consuming, or unclonable to clone by other methods have been cloned. PMID- 2251112 TI - A novel repeated DNA sequence located in the intergenic regions of bacterial chromosomes. AB - We report the discovery of a novel group of highly conserved DNA sequences located within the intergenic regions of the chromosomes of Escherichia coli, Salmonella typhimurium and other bacteria. These intergenic repeat units (IRUs) are 124-127 nucleotides long and have the potential to form stable stem-loop structures. The location of these sequences within the intergenic regions is variable with respect to known or putative signals for transcription and translation of the flanking genes. Some of the IRU sequences are transcribed, others are probably not. The structure and possible functions of these sequences are discussed in relation to palindromic units and other repeated DNA sequences in bacteria. PMID- 2251113 TI - Initiation of transcription of the erythroid promoter of the porphobilinogen deaminase gene is regulated by a cis-acting sequence around the cap site. AB - Although the erythroid-specific promoter of human porphobilinogen deaminase [PBGD] gene has no TATA box, transcription is initiated at a single nucleotide. Using 5' and 3' deletions and point mutations, we have identified an element, located around the initiation site, which is necessary and sufficient for 'in vitro' accurate initiation of transcription. This 15 bp element extends 1 bp 5' and 14 bp 3' from the initiation site. It is composed of two regions, a proximal region centred on the cap site and a distal region which bears homology with the TdT initiator element. We show that a nuclear factor, present both in erythroid and non erythroid cells, binds the distal PBGD initiator element. Lack of heat inactivation suggests that initiation of transcription mediated by this element is not TFIID dependent. By transfection into erythroid cells, we also show that the proximal PBGD initiator element is essential for the selection of the initiation site but not for the regulation of transcription of the PBGD erythroid promoter during erythroid differentiation. PMID- 2251114 TI - Frameshift autoregulation in the gene for Escherichia coli release factor 2: partly functional mutants result in frameshift enhancement. AB - The regulation of release factor 2 (RF-2) synthesis in Escherichia coli occurs, at least in part, through autoregulatory feedback exerted at a unique frameshifting step required during RF-2 translation. We have constructed fusions between the genes for RF-2 and E. coli trpE which make direct measurement of frameshifting efficiency possible since both products of regulation, the termination product and the frameshift product, are stable. The addition of purified RF-2 to in vitro expressions of these fusion genes was found to result in decreased frameshifting and increased termination at the regulation site. The frame-shifted trpE-RF-2 products synthesized from these fusions are unique with respect to their functional release factor activities; when tested in assays of two intermediate steps of translational termination, they were found to be partially active for the function of ribosome binding, but inactive for peptidyl tRNA hydrolysis (release). These are the first examples of release factor mutants selectively active for only one of these function. In vivo these chimeric proteins promote large increases in frameshifting at the RF-2 frameshift region, thereby reversing normal negative autoregulatory feedback and instead supporting fully efficient frameshifting in their own synthesis. This activity provides new evidence for the importance of ribosomal pausing in directing efficient frameshifting at the RF-2 frameshift region. PMID- 2251115 TI - Polypurine/polypyrimidine hairpins form a triple helix structure at low pH. AB - 1D and 2D NMR investigations of the 15 residue deoxynucleotide sequence d(TCTCTC TTT-GAGAGA) show that above pH = 6.5 the molecule adopts a B-form hairpin conformation. As the pH is lowered below 6.5 molecules progressively associate in pairs to form a partially triple helical, partially single stranded structure in which the bases of the oligopyrimidine d(TC)3 tract from one molecule form Hoogsteen pairs with the d(G-A)3 tract of the other. Imino protons of protonated cytosines can be observed at very low field (approximately 15 ppm). The enthalpy of triplex formation was estimated by NMR techniques to be -16 kcal mol-1. Intense H6 to H3' cross peaks from residues in all three strands suggest the presence of N-type sugars at some but not at all possible sites. Surprisingly strong cross peaks between H5' or H5" and non-exchangeable base protons are also observed. These suggest that certain of the O5'-C5'-C4'-C3' phosphate backbone torsion angles (gamma) are unusual. PMID- 2251116 TI - Codon recognition in polypeptide chain termination: site directed crosslinking of termination codon to Escherichia coli release factor 2. AB - An RNA synthesized in vitro was positioned on the Escherichia coli ribosome at the P site with tRNAala, and with a termination codon, UAA, as the next codon in the A site. Such a complex bound stoichiometric amounts of release factor 2 (RF 2); a corresponding RNA with UAC in place of UAA was not a template for the factor. An RNA containing 4-thio-UAA in place of the UAA supported binding of RF 2, and this has allowed site-directed crosslinking from the first position of the termination codon to answer two long standing questions about the termination of protein biosynthesis, the position of the termination codon and its proximity to the release factor during codon recognition. An RF-2.mRNA crosslinked product was detected, indicating the release factor and the termination codon are in close physical contact during the codon recognition event of termination. The 4-thio-U crosslinked also to the ribosome but only to the 30S subunit, and the proteins and the rRNA site concerned were identified. RF-2 decreased significantly the crosslinking to the ribosomal components, but no new crosslink sites were found. If the stop codon was deliberately displaced from the decoding site by one codon's length then a different pattern of crosslinking in particular to the rRNA resulted. These observations are consistent with a model of codon recognition by RF-2 at the decoding site, without a major shift in position of the codon. PMID- 2251117 TI - Characterization of a DNA binding protein of bacteriophage PRD1 involved in DNA replication. AB - Escherichia coli phage PRD1 protein P12, involved in PRD1 DNA replication in vivo, has been highly purified from E. coli cells harbouring a gene XII containing plasmid. Protein P12 binds to single-stranded DNA as shown by gel retardation assays and nuclease protection experiments. Binding of protein P12 to single-stranded DNA increases about 14% the contour length of the DNA as revealed by electron microscopy. Binding to single-stranded DNA seems to be cooperative, and it is not sequence specific. Protein P12 also binds to double-stranded DNA although with an affinity 10 times lower than to single-stranded DNA. Using the in vitro phage phi 29 DNA replication system, it is shown that protein P12 stimulates the overall phi 29 DNA replication. PMID- 2251118 TI - Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. AB - PRP2 protein of Saccharomyces cerevisiae is required for the pre-mRNA splicing reaction but not for the early stages of spliceosome assembly. Using anti-PRP2 antibodies we demonstrate that PRP2 protein is associated with spliceosomes prior to, and throughout step 1 of the splicing reaction. Heat-inactivated prp2 protein, by contrast, does not seem to associate with spliceosomes. By elution of electrophoretically distinct spliceosomal complexes from non-denaturing gels we identify the specific complex with which PRP2 initially interacts in the pathway of spliceosome assembly. PMID- 2251119 TI - Mouse U14 snRNA is encoded in an intron of the mouse cognate hsc70 heat shock gene. AB - Mouse U14 snRNA (previously designated mouse 4.5S hybRNA) is an evolutionarily conserved eukaryotic low molecular weight RNA capable of intermolecular hybridization with both homologous and heterologous 18S rRNA (1). A single genomic fragment of mouse DNA containing the U14 snRNA gene(s) has been isolated from a Charon 4A lambda phage mouse genomic library and sequenced. Results have surprisingly revealed the presence of three U14 snRNA-homologous regions positioned within introns 5, 6, and 8 of the mouse cognate hsc70 heat shock gene. Comparative analysis with the previously reported rat and human cognate hsc70 genes revealed a similar positioning of U14 snRNA-homologous sequences within introns 5, 6 and 8 of the respective rat and human genes. The U14 sequences contained in all three introns of all three organisms are highly homologous to each other and well conserved with respect to the diverging intron sequences flanking each U14-homologous sequence. Comparison of the mouse U14 snRNA sequence with the U14 DNA sequences contained in the three mouse hsc70 introns indicates that intron 5 is utilized for U14 snRNA synthesis in normally growing mouse ascites cells. Analysis of the determined mouse, rat, and human U14-homologous sequences and the upstream and downstream flanking regions did not reveal the presence of any previously defined RNA polymerase I, II, or III binding sites. This suggests that either higher eukaryotic U14 snRNA is transcribed from a unique transcriptional promoter sequence, or alternatively, is generated by intron processing of the hsc70 pre-mRNA transcript. PMID- 2251120 TI - Recombinant hnRNP protein A1 and its N-terminal domain show preferential affinity for oligodeoxynucleotides homologous to intron/exon acceptor sites. AB - The reported binding preference of human hnRNP protein A1 for the 3'-splice site of some introns (Swanson and Dreyfuss (1988) EMBO J. 7, 3519-3529; Mayrand and Pederson (1990) Nucleic Acids Res. 18, 3307-3318) was tested by assaying in vitro the binding of purified recombinant A1 protein (expressed in bacteria) to synthetic oligodeoxynucleotides (21-mers) of suitable sequence. In such a minimal system we find preferential binding of protein A1 to oligodeoxynucleotide sequences corresponding to the 3'-splice site of IVS1 of human beta-globin pre mRNA and of IVS1 of Adenovirus type 2 major late transcript. Mutation studies demonstrate that the binding specificity is dependent on the known critical domains of this intron region, the AG splice site dinucleotide and polypyrimidine tract, and resides entirely in the short oligonucleotide sequence. Moreover specific binding does not require the presence of other hnRNP proteins or of snRNP particles. Studies with a truncated recombinant protein demonstrated that the minimal protein sequence determinants for A1 recognition of 3'-splice acceptor site reside entirely in the N-terminal 195 aa of the unmodified protein. PMID- 2251121 TI - M.Smal is an N4-methylcytosine specific DNA-methylase. AB - An enzymatic activity rendering DNA immune to the action of the Smal restriction endonuclease in the presence of S-adenosyl-L-methionine has been detected in Serratia marcescens Sb. This methylase, M.Smal, modifies the second cytosine residue of the substrate sequence CCCGGG yielding N4-methylcytosine. PMID- 2251122 TI - Formation of intramolecular triplex in homopurine-homopyrimidine mirror repeats with point substitutions. AB - We have used two-dimensional gel electrophoresis to study the structural transition to the triplex H form of sequences 5'-AAGGGAGAAXGGGGTATAGGGGYAAGAGGGAA 3' where X and Y are any DNA bases. The transition was observed at acid pH under superhelical stress. For X = Y = A or X = Y = G the sequences corresponded to homopurine-homopyrimidine mirror repeats (H-palindrome) which are known to adopt the H form under acid pH and superhelical stress. We have shown that the H form is actually formed for all X and Y, though in cases other than X = Y = A and X = Y = G the transition requires larger negative superhelical stress. Different substitutions require different superhelicity levels for the transition to occur. Theoretical analysis of the data obtained made it possible to estimate the energy cost of triplex formation due to all possible mismatched base triads. PMID- 2251123 TI - UV-induced cross-linking of Tet repressor to DNA containing tet operator sequences and 8-azidoadenines. AB - The synthesis of 8-azido-2'-deoxyadenosine-5'-triphosphate is described. The photoreactive dATP analog was characterized by thin layer chromatography, proton resonance spectroscopy, infrared spectroscopy and UV spectroscopy. Its photolysis upon UV irradiation was studied. After incorporation of this dATP analog into DNA containing the tet operator sequence the investigation of the interactions between tet operator DNA and Tet repressor protein by UV photocross-linking becomes possible. Photocross-linking of protein to DNA was demonstrated by the reduced migration of the DNA in SDS polyacrylamide gel electrophoresis. Addition of the inducer tetracycline prior to UV irradiation significantly reduces the DNA protein cross-linking rate. The long wave UV light applied here does not significantly alter the DNA or the protein under the photocross-linking conditions. PMID- 2251124 TI - Transcriptional regulation of gene expression in Tetrahymena thermophila. AB - The only well-characterized study of gene expression in Tetrahymena thermophila (1) demonstrates that the temperature dependent expression of the Ser H3 gene is regulated at the level of mRNA stability. A run-on transcription assay was developed to determine if regulation of RNA stability was a major mechanism regulating gene expression in Tetrahymena or if transcriptional regulation dominates. The relative transcriptional activities of 14 Tetrahymena genes were determined in different physiological/developmental states (growing, starved and conjugating) in which many of the genes showed striking differences in RNA abundance. In every case except Ser H3, changes in transcription accompanied changes in RNA abundance. Thus differential transcription, not differential RNA degradation, is the major mechanism regulating RNA abundance in Tetrahymena. PMID- 2251125 TI - Statistical analysis of nucleotide sequences. AB - In order to scan nucleic acid databases for potentially relevant but as yet unknown signals, we have developed an improved statistical model for pattern analysis of nucleic acid sequences by modifying previous methods based on Markov chains. We demonstrate the importance of selecting the appropriate parameters in order for the method to function at all. The model allows the simultaneous analysis of several short sequences with unequal base frequencies and Markov order k not equal to 0 as is usually the case in databases. As a test of these modifications, we show that in E. coli sequences there is a bias against palindromic hexamers which correspond to known restriction enzyme recognition sites. PMID- 2251127 TI - Nucleotide sequence of two rice prolamin cDNAs. PMID- 2251126 TI - The structure of a subterminal repeated sequence present on many human chromosomes. AB - All telomeres which have been studied consist of an array of simple G/C rich repeats. Human telomeres were shown to share sequence similarity with those of lower eukaryotes by cross-hybridization and human telomeric sequences have been cloned by complementation of telomere function in yeast. Analysis of human telomeric sequences cloned in this way is described here. The terminal part of the cloned human telomeric DNA consists of an array of simple repeats, principally of the sequence TTAGGG and derivatives. The very terminal part consists of yeast-type telomeric repeats which suggests that the human telomeric sequences have acted as a primer for the addition of additional telomeric repeats in the yeast. Subterminal sequences are shared between a number of clones and in situ data shows that these subterminal sequences are present at several different chromosomal ends. Related sequences are present at internal as well as telomeric positions. Differences in the hybridization patterns of subterminal sequences in somatic compared to germ-line tissues are described which indicate differential modification of these sequences during development. PMID- 2251128 TI - Nucleotide sequence of an actinidin genomic clone. PMID- 2251129 TI - Nucleotide sequence of the unassigned reading frame urf a in the mitochondrial genome of three Schizosaccharomyces pombe strains. PMID- 2251130 TI - Nucleotide sequence of Rhizobium loti nodC. PMID- 2251131 TI - Nucleotide sequence of Rhizobium loti nodI. PMID- 2251132 TI - Nucleotide sequence of cDNA covering the complete coding part of the human vimentin gene. PMID- 2251133 TI - Nucleotide sequence of the Streptococcus pneumoniae ung gene encoding uracil-DNA glycosylase. PMID- 2251134 TI - Cloning and sequencing of the 3'-terminal region of potato virus YN (Russian isolate) RNA genome. PMID- 2251135 TI - Molecular cloning and sequencing of cDNA for rat cystatin beta. PMID- 2251136 TI - Nucleotide sequence of rice dwarf virus (RDV) genome segment S3 coding for 114 K major core protein. PMID- 2251137 TI - Nucleotide sequence of an HLA-A1 gene. PMID- 2251138 TI - Nucleotide sequence of an HLA-Bw57 gene. PMID- 2251139 TI - The nucleotide sequence of a human tRNA(Glu) gene. PMID- 2251140 TI - Nucleotide sequence of the Adh gene of Drosophila lebanonensis. PMID- 2251141 TI - The complete nucleotide sequence of the GDVII strain of Theiler's murine encephalomyelitis virus (TMEV). PMID- 2251142 TI - A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line. PMID- 2251143 TI - The nucleotide and derived amino acid sequence of the omp2 gene of Chlamydia trachomatis serovar E. PMID- 2251144 TI - Nucleotide sequence of the epsilon-subunit of the mouse muscle nicotinic acetylcholine receptor. PMID- 2251145 TI - Yeast mitochondrial DNA polymerase is related to the family A DNA polymerases. PMID- 2251147 TI - Nucleotide sequence of the gene encoding rhesus monkey (Macaca mulatta) interleukin-3. PMID- 2251146 TI - Sequence of the Trichoderma viride phosphoglycerate kinase gene. PMID- 2251148 TI - Sequence of the cDNA encoding rat furin, a possible propeptide-processing endoprotease. PMID- 2251149 TI - Nucleotide sequence of an altered virulence potato virus Y coat protein gene (PVYH strain). PMID- 2251150 TI - Nucleotide sequence of the araD gene of Escherichia coli K12 encoding the L ribulose 5-phosphate 4-epimerase. PMID- 2251151 TI - Primary structure of ovine tumor necrosis factor alpha cDNA. PMID- 2251152 TI - Nucleotide sequence of the maize Mutator element, Mu8. PMID- 2251153 TI - Sequence of a cDNA encoding Syrian hamster islet amyloid polypeptide precursor. PMID- 2251154 TI - Selenocysteine inserting tRNAs are likely generated by tRNA editing. PMID- 2251155 TI - Nucleotide sequence of tRNAval (GUU) from Arabidopsis thaliana. PMID- 2251156 TI - A rapid test for V(D)J recombinase activity. PMID- 2251157 TI - Comparative sequence analysis of mammalian factor IX promoters. PMID- 2251159 TI - A swift and facile radiosynthesis of [alpha-32P]-3'-azido-3'-deoxythymidine 5' triphosphate (AZT triphosphate). PMID- 2251158 TI - A simple strategy to generate small deletions using Bal31 nuclease. PMID- 2251160 TI - Use of psoralen as extinguisher of contaminated DNA in PCR. PMID- 2251161 TI - Restriction endonuclease from thermophilic bacterial species. II. Isolation and characterization of BsiBI. PMID- 2251162 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2251164 TI - Prisoners of the system.... PMID- 2251163 TI - Conflict of interests. PMID- 2251165 TI - . . . finding a better system. PMID- 2251166 TI - Dangerous ground. PMID- 2251167 TI - Children's rights. PMID- 2251168 TI - Patching up the NHS. PMID- 2251170 TI - A common-sense duty rota. PMID- 2251171 TI - A hard decision. PMID- 2251169 TI - Regaining a basic pleasure. Care study. PMID- 2251172 TI - Demystifying masturbation. PMID- 2251173 TI - Labour's prescription for grading appeals. Interview by Andrew Cole. PMID- 2251174 TI - Researching chronic fatigue. PMID- 2251175 TI - Open learning. No through road?. Interview by Laura Swaffield. PMID- 2251176 TI - Open learning. The role of the tutor. PMID- 2251178 TI - Extradural anaesthesia and spinal surgery. PMID- 2251177 TI - I shall overcome. Interview by Daloni Carlisle. PMID- 2251180 TI - Mental handicap nursing. Making care count. The heart of the matter. PMID- 2251179 TI - Mental handicap nursing. Making care count. A long day's journey. PMID- 2251181 TI - Prevention and detection: what's needed now? PMID- 2251182 TI - Clinical trial procedures clarified. PMID- 2251183 TI - Piper fatigue scale available for clinical testing. PMID- 2251184 TI - Management of cutaneous reactions and mechanical complications of central venous access devices in pediatric patients with cancer: algorithms for decision making. AB - Surgically placed central venous catheters (CVCs) facilitate the delivery of medication and nutrition support for patients with malignant disease. There is little information regarding allergic reactions to materials used for standard CVC care or about mechanical complications associated with CVC use. This study describes allergic and mechanical complications that occurred in a series of 288 CVCs implanted in 238 pediatric patients with malignant disease. There were 20 episodes of cutaneous reactions to standard central line dressing care (alcohol/povidone-iodine/TegadermTM), 13 incidents of catheter exit site infections, and 14 experiences of mechanical breakage in external CVCs. Complications were managed from algorithms that provided a systematic sequence of nursing interventions for alternative catheter dressing techniques and line repair. Only two CVCs were removed because of progressive infection, and one catheter was removed because of occlusion after repair. PMID- 2251185 TI - Teaching oncology nurses about epidural catheters. AB - Medication administered through epidural catheters for control of acute and chronic pain is becoming a common practice in some hospitals. The care of epidural catheters usually is not included in basic nursing education curriculum. In settings where RNs will administer medication by this route or monitor patients receiving epidural medication, adequate preparation of the RN staff is vital to ensure that the catheter remains intact, that therapy is administered without complications, and that the patient has optimal pain relief. Instruction should include information on the catheter's purpose, administration techniques, pharmacology of the drug, side effects, and monitoring techniques. For program planning, a multidisciplinary group set criteria on which the policy and procedure for administration of epidural analgesia were based. The educational program focused on administering morphine sulfate through an epidural catheter and on safe discontinuation of the catheter. PMID- 2251186 TI - A multifaceted rehabilitation program for women with cancer. AB - A multifaceted rehabilitation program for women diagnosed with cancer includes a personal fitness plan, aerobic exercise classes, journaling, and a six-day environmental wilderness experience. The program's purpose is for participants to learn how to cope with uncertainties in life and to promote a wellness concept for living with cancer. This is achieved through successfully meeting the challenges of the program. A descriptive study, using journal entries of the pilot group's 12 women with breast cancer, provides insight into participants' views of the program. Their responses described: personal growth through succeeding at new and difficult experiences; normalization engendered by communicating with others having cancer; exhilaration at focusing on challenging events external to personal health problems; and courage that overrode their fears of facing what seemed impossible. PMID- 2251187 TI - Learning needs of Oncology Nursing Society members. AB - The ONS mission is to promote excellence in oncology nursing. In its effort to carry out this mission, ONS has a responsibility to provide high-quality continuing education (CE) for cancer nurses. An important first step in the provision of quality CE is determining learners' needs. The ONS Continuing Education Provider Committee (CEPC) conducted a comprehensive educational needs assessment of the ONS membership during 1988. Preferred content (98 topics were included), level of content needed (basic versus advanced), preferred teaching learning methods, and items related to the logistics of CE programs (i.e., preferred length, days of week, employer reimbursement) were assessed. Half of the 1988 ONS membership (6,500) was randomly surveyed, with a 30.8% (2,002) return rate. Analysis revealed the five topics of most interest to be oncologic emergencies, pain, critical care of the patient with cancer, legal issues, and advanced nursing practice roles. PMID- 2251188 TI - Factors contributing to health promotion behaviors among African-American men. AB - Few studies reported in the literature address healthcare trends of African American men. A study of health promotion behaviors of African-American men was undertaken using a health beliefs framework. The study examined the cancer related knowledge, attitudes, and perceptions (KAP) of a select group of African American men to evaluate their influence on health promotion behaviors. The health beliefs framework was very useful in predicting the health promotion behaviors of African-American men. Significant relationships were observed between the variables of knowledge of early warning signs of cancer, attitudes related to screening procedures, perceptions of seriousness of cancer, and cancer risk reduction and early detection health promotion behaviors. The results reinforce earlier reports indicating the pronounced effects of knowledge, attitudes, and perceptions on the use of health-promoting activities. PMID- 2251189 TI - Predictors of older adults' participation in fecal occult blood screening. AB - This study describes variables that predicted participation in fecal occult blood screening. Orem's theory provides the conceptual basis for this descriptive research study. As part of the research, the American Cancer Society's (ACS) colorectal cancer educational program was given to 171 participants of a congregate meal program. Forty-seven percent of the respondents submitted specimens for occult blood testing. Female gender was the only demographic variable found to predict participation in the fecal occult blood screening. The ability to use the telephone, shop for groceries or clothes, and clean house were associated with submission of a fecal specimen. Respondents who assessed their eyesight and hearing as good did not differ from other respondents in regard to submitting fecal specimens. Implications for health education, early detection, and oncology and gerontological nursing are identified. PMID- 2251190 TI - Nurses' compliance with American Cancer Society guidelines for cancer prevention and detection. AB - This study aimed to ascertain the extent to which female nurses comply with American Cancer Society (ACS) guidelines and whether their rate of compliance is related to either age or education. A sample of 3,226 Florida nurses received the Health Habits Assessment Survey (HHAS), a nine-item questionnaire that assesses compliance with selected ACS guidelines. A total of 559 usable forms were received from female nurses. Results indicated that only 28% of RNs practice breast self-examination (BSE) monthly. Of nurses 40-49 years old, 64% reported having a mammogram in the past two years. In the over-50 group, 57% reported having a mammogram in the past year. Only 21% reported no Pap smear in the past year (and no hysterectomy). Only 47% of RNs over 40 reported a digital rectal exam in the past year. Of RNs over 50, only 47% reported having their stools examined for blood during the previous year, and only 19% had a proctosigmoidoscopic exam in the past five years. Thirty-five percent reported using sunscreen all or most of the time, while another 27% reported using sunscreen 50%-90% of the time. No significant relationships were found between cancer prevention and detection practices and either age or educational level. Results suggest that RNs are not doing all they could to protect themselves against cancer. PMID- 2251191 TI - Use of amphotericin B in immunosuppressed patients with cancer. Part One: Pharmacology and toxicities. AB - Potentially fatal fungal infections account for most of the prolonged fevers found in immunosuppressed patients with cancer. Amphotericin B (AmB) is the most effective drug available to treat these infections. This article, Part One of two parts, reviews the biochemical properties of AmB and its dosage and administration. Major toxicities and common side effects are discussed. Part Two uses the pharmacodynamics addressed in Part One as a basis for planning nursing interventions to prevent or suppress adverse reactions. PMID- 2251192 TI - Use of amphotericin B in immunosuppressed patients with cancer. Part Two: Pharmacodynamics and nursing implications. AB - Nursing care of patients receiving amphotericin B (AmB) must address the underlying condition of the immunosuppressed patient with cancer and the iatrogenic responses induced by the drug. This review, the companion to "Part One: Pharmacology and Toxicities," focuses on nursing actions that consider both the drug's specific pharmacodynamics and the altered human responses caused by disease and therapy. Maximization of drug effectiveness and minimization of drug toxicity are key care goals. PMID- 2251193 TI - Groshong catheter or implanted port: which is better for you? PMID- 2251195 TI - Comfort pillows. PMID- 2251194 TI - Oncology Nursing Society Position Paper on cancer pain. Part II. PMID- 2251196 TI - How to create a catheter pocket. PMID- 2251197 TI - Enhanced hyperpigmentation with combination chemotherapy. PMID- 2251198 TI - 5-FU and leucovorin: unexpected side effects. PMID- 2251199 TI - Combination antiemetic therapy. PMID- 2251200 TI - Facilitating communication in a radiation therapy treatment center. PMID- 2251201 TI - Maintaining independence. PMID- 2251202 TI - Chemotherapy spills on carpet. PMID- 2251203 TI - Enabling independence in the bone marrow transplant patient population. PMID- 2251204 TI - The get-away room. PMID- 2251205 TI - Causes of accidental exposure to antineoplastic agents. PMID- 2251206 TI - Spanish medication card. PMID- 2251207 TI - [Serum cholic acid levels in patients with acute leukemia]. AB - In 34 patients (16 women and 18 men) with acute leukaemias (8 with acute lymphoblastic leukaemia and 26 with acute myeloblastic leukaemia), as yet untreated, the serum levels were determined of conjugated cholic acid, bilirubin, aspartate aminotransferase (AspAT), alanine aminotransferase (AlAT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and cholinesterase (Chol). Serum conjugated cholic acid level was determined by radioimmunoassay. The mean values of AP and Chol activity were within the range of normal values in this laboratory, the values of AspAT and AlAT were slightly above this range, and LDH value exceeded twice this normal range. The mean bilirubin concentration was within normal range. The greatest changes were noted in conjugated cholic acid values, the mean value exceeded five times the upper normal range (1.0 mumol/l). In 30 patients (88%) the conjugated cholic acid level in the serum was above 1.0 mumol/l, in the remaining 4 cases it was above the mean value for the control group. No correlation was found between conjugated cholic acid and any of the determined parameters. These results point out that the serum level of conjugated cholic acid may be a valuable parameter for assessment of hepatocellular function in acute leukaemias. PMID- 2251208 TI - [Evaluation of the effect of yohimbine, an alpha2 adrenolytic drug, on gastric emptying in obesity]. AB - In 15 obese subjects (11 women and 4 men) the effect was assessed of yohimbine, an alpha 2-adrenolytic drug on gastric emptying after solid food. After oral administration of 15 mg of the drug no significant change was observed in this emptying in relation to placebo. PMID- 2251209 TI - [Renin activity and aldosterone level in the plasma of children with lipoid nephrosis]. AB - In 16 children with steroid-responsive nephrotic syndrome (with minimal changes in the glomeruli) the plasma renin activity and aldosterone level were determined during recurrence of the nephrotic syndrome at the stage of oedema increase (FEN alpha 0.25%) and in early period of remission. Plasma renin activity was raised in all cases suggesting presence of hypovolaemia. Since it was not possible to establish a correlation between plasma renin activity and albumin level, as well as between this activity and aldosterone level, and aldosterone level and sodium excretion it may be surmised that the renin-angiotensin-aldosterone system has no decisive role in the pathogenesis of the nephrotic syndrome. The mechanism of oedema development is doubtlessly more complex. PMID- 2251210 TI - [Arrhythmia and silent myocardial ischemia in patients after myocardial infarction]. AB - In a group of 37 patients (30 men and 7 women aged from 36 to 67 years, men age 50.3) after a first acute myocardial infarction the frequency was analysed of the episodes of silent myocardial ischaemia with ST depression, and its correlation with arrhythmia was studied during outpatient ECG monitoring and exercise test on cycle ergometer. Outpatient ECG monitoring during 24 hours was done with a recorder Oxford Medilog MR-14 AM System 8-12 weeks after the onset of infarction. In the same patients the exercise test on cycle ergometer (KF-12 Medicor) was done by graded exercise method with workload increasing by 25 Watt every 3 minutes. The test was terminated after achieving 85% maximal heart rate or appearance of limiting signs. Each episode of ST depression by 1.0 mm or more lasting over 1 minute with horizontal or sloping ST depression 80 msec from point J was regarded in both cases as ischaemic. During outpatient ECG monitoring it was observed that 30 out of 37 (81.1%) had 138 episodes of ST depression, including 45 (32.6%) associated with pain and 93 (67.9%) painless (p less than 0.02). The mean maximal ST depression during painful and painless episodes was respectively 3.4 +/- 1.3 mm and 2.9 +/- 1.1 mm (p less than 0.03). Out of 30 patients 7 (23.3%) had 54 episodes of various arrhythmias, with bursts of ventricular ectopic beats, in one patient supraventricular tachycardia and in another one grade II atrioventricular block developed. These patients had also isolated ventricular ectopic beats. In 6 patients (20.0%) arrhythmia was temporarily associated with signs of ischaemia with ST depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251211 TI - [Operative endoscopy and ultrasonography in the treatment of pancreatic diseases]. PMID- 2251213 TI - [Blood levels of insulin and growth hormone during exercise test in obese patients with normal glucose tolerance and with diabetes mellitus after food intake and fasting]. AB - Ten obese patients with normal glucose tolerance, 11 obese with type II diabetes and 15 normal non-obese controls were studied. The submaximal exercise test was made before fasting in all the mentioned 3 groups of patients and in the obese patients after a 10 days fast. The exercise on normal diet did not cause any changes in serum insulin in all groups. The growth hormone secretion, however, rose in all the groups studied. Fasting did not modify the insulin secretion following the exercise in both groups of the obese. The growth hormone secretion, exercise stimulated, was elevated by fasting as well in the obese with normal and abnormal glucose tolerance. We believe that a marked energetic deficit due to exercise on fasting may supplement the deficit of the growth hormone which usually occurs in obesity. This might be therapeutically usefull in treating obesity in selected cases. PMID- 2251212 TI - [Immunosuppressive effect of heparin]. PMID- 2251214 TI - [Difficulties in the diagnosis of pancreatic cancer using endoscopic retrograde cholangiopancreatography]. AB - Difficulties are presented which the authors met on ERCP-evaluation of the pancreatic cancer. 64 cases were analyzed of the diagnosed cancer, then confirmed on surgery, histopathologically+ and post mortem. Differentiation of the cancer from chronic pancreatitis was most difficult with the false positive results being 20.3. PMID- 2251215 TI - [Effect of peritoneal dialysis on respiratory function in patients with chronic renal failure]. AB - In 17 patients with end stage renal failure the effect was studied of a single peritoneal dialysis on the respiratory function, in the sitting and the recumbent position of the body. After the infusion of 2 liters of the dialysis fluid into the peritoneal cavity arterial PaO2 fell as well as the functional residual capacity, but the alveolar/arterial oxygenation difference (A-alpha)O2 rose. The most marked changes accompanied by dyspnea occurred in most patients in the sitting position. The inspiratory residual volume (IRV) increase reflects a better diaphragmatic function. The usefulness of aminophylline is discussed which not only dilates the bronchi but also improves the contractibility of the diaphragmatic muscle. PMID- 2251216 TI - [Solitary metastasis of clear cell carcinoma of the kidney to the thyroid gland]. AB - Two rare cases of solitary metastasis to the thyroid of the clarocellular carcinoma of the kidney are described. The diagnostic difficulties are presented as well as the surgical treatment and the katamnesis of the patients. A short review of the literature has been given. PMID- 2251217 TI - [Hodgkin's disease and non-Hodgkin's lymphoma in 2 sisters]. AB - For the first time in the Polish medical literature an appearance is presented of malignant lymphogranulomatosis and of a non-Hodgkin lymphoma in two sisters. A discussion on the etiology of the condition is presented on the ground of the cytogenic studies and tissue compatibilities antigens as well as of the literature of the subject. Genetic background of the two different diseases in two sisters is stressed. PMID- 2251218 TI - [Colony stimulating factor (CSF)--various aspects of its therapeutic use]. PMID- 2251219 TI - [Mechanisms of immunologic deposits in glomerulonephritis]. PMID- 2251220 TI - [Dr. Michal Litynski (1906-1989]. PMID- 2251221 TI - Characterization of muscarinic cholinergic receptors in membrane preparations from rat prostatic adenocarcinoma. AB - The binding characteristics of 3H-quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions from R-3327 Dunning tumors (H and AT 1 sublines); ventral, dorsolateral prostate; and urinary bladder of the rat were studied. QNB binding to all preparations, except from AT-1 tumors, was specific, saturable, and of high affinity. The AT-1 tumors completely lacked specific QNB binding. The muscarinic receptor density in H tumors was twofold and twentyfold higher than that in the ventral prostate and dorsolateral prostate respectively. The receptor density in the urinary bladder was approximately twofold higher than that in H tumors. The Kd values in H tumors and ventral prostate were very similar and significantly higher than that in dorsolateral prostate or the urinary bladder. QNB binding in H tumors was strongly inhibited by classical muscarinic receptor antagonists atropine and scopolamine, but poorly by the agonists carbacholine and pilocarpine. In contrast to scopolamine or atropine, inhibition by pirenzepine and AF-DX116 was relatively low. These data indicate that the muscarinic receptor in Dunning H tumors is of M3 type. PMID- 2251222 TI - A case-control study of prostatic cancer in Kyoto, Japan: sexual risk factors. AB - A case-control study on prostatic cancer was conducted in Kyoto, Japan, from 1981 1984, including 100 patients with prostatic cancer (PC) and age, hospital, and date-of-admission matched controls of benign prostatic hyperplasia (BPH) patients and general hospital patients. Analysis of several sexual factors obtained through a self-administered questionnaire revealed the following observations: 1) cancer patients had fewer sex partners before marriage (relative risk, RR = 0.35; 95% confidence interval: 0.13-0.93) than the hospital controls; 2) they had more vigorous sexual activities in the third (RR = 2.89; 1.01-8.28) and fourth decades of life (RR = 2.26: 1.03-4.95) than hospital controls, but no significantly different sexual activities from controls in other decades; 3) they had less frequent orgasms (RR = 2.55; 1.11-5.83) than BPH controls or (RR = 4.96: 1.78 13.9) hospital controls, and sexual intercourse appeared to be less satisfactory (RR = 2.08: 1.05-4.13) than that of hospital controls; and 4) they had less frequent episodes of sexually transmitted diseases (RR = 0.36: 0.16-0.83) than BPH controls. Marital status, fertility, ejaculation, masturbation, nocturnal emission, contraceptive use, and wife's episodes of sexually transmitted disease were not linked to prostatic cancer risk. PMID- 2251223 TI - Reduction of testosterone availability to 5 alpha-reductase by human sex hormone binding globulin in the rat ventral prostate gland in vivo. AB - The present studies assess the effects of human sex hormone-binding globulin (SHBG) on the conversion of [3H]testosterone (T) into dihydrotestosterone (DHT) in rat ventral prostate gland in vivo using a constant aortic infusion technique. The DHT/T ratio was determined using two-dimensional thin-layer chromatography (TLC), and these results were confirmed with reverse-phase high-performance liquid chromatography. The prostatic gland DHT/T ratio was 2.1 +/- 0.4, 1.3 +/- 0.2, 0.24 +/- 0.02, or 1.1 +/- 0.2, following a 60 sec aortic perfusion of [3H]testosterone dissolved in either Krebs-Henselite buffer (KHB), 5 g/dl human serum albumin (HSA), human pregnancy serum (HPS), or heat inactivated HPS, respectively. Heat inactivation (60 degrees C, 60 min) selectively denatured SHBG in HPS. The distribution of [3H]testosterone in rat ventral prostate was examined with thaw-mount light in microscopic autoradiography. Following an aortic perfusion of [3H]testosterone in buffer alone, the radiolabeled steroid was uniformly distributed among the epithelial and stromal compartments. However, the [3H]steroid hormone was selectively sequestered in the stromal compartment following aortic perfusion of HPS. In conclusion, these studies demonstrate that human SHBG markedly restricts the availability of circulating testosterone to 5 alpha-reductase in the prostate gland in vivo and that the presence of SHBG in serum causes the selective sequestration of the steroid hormone within the stromal compartment of the gland in vivo. PMID- 2251224 TI - Differential effects of growth factor antagonists on neoplastic and normal prostatic cells. AB - Growth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen-dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen-independent AT-2 subline of the Dunning R-3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT-2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells. PMID- 2251226 TI - Practice guidelines: a surgeon's perspective. PMID- 2251225 TI - Family history and the risk of prostate cancer. AB - A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P less than .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11-fold increased risk of developing prostate cancer. Recognizing that 9-10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease. PMID- 2251227 TI - Intraarticular fractures of the calcaneus: diagnosis and surgical management. PMID- 2251228 TI - Fractures of the neck of the talus. AB - Talar neck fractures should be managed with meticulous attention to detail, and anatomical reduction is mandatory. Most type I fractures can be treated closed, unless there is loss of reduction, but type II, III, and IV, especially if displaced, usually require open reduction and internal fixation. Closed reduction may be attempted, but if the reduction is lost, or satisfactory reduction cannot be obtained, open reduction should be performed. Two incisions may be necessary to confirm accurate anatomical reduction. Poor results occur because of avascular necrosis, malunion, subtalar arthritis, and infection. Attention to detail can decrease the incidence of the latter three of these complications; the development of avascular necrosis does not seem to be related to the type of treatment. Though the most serious complication, avascular necrosis, may not require surgical intervention, many of the authors' patients have done well with conservative treatment. PMID- 2251229 TI - Effect of an unrestricted knee-ankle-foot orthosis on the stance phase of gait in healthy persons. AB - Twenty healthy women (mean age: 25 +/- 3.6 years) were studied for postural adaptations produced when walking with unrestricted knee-ankle-foot orthoses. Stride characteristics, motion, floor reaction forces and their torques, and indwelling electromyographic activity of the lower gluteus maximus, as well as the long head of the biceps femoris, vastus lateralis, and soleus muscles were all measured during barefoot and orthosis walking. Wearing a knee-ankle-foot orthosis increased stride length and decreased cadence and stance duration. The subjects walked in slightly more plantar flexion, knee flexion, and hip flexion, while increasing the duration of the corresponding floor reaction torques, resulting in an activity increase of the vastus lateralis, soleus, and biceps femoris muscles. These results, obtained in healthy subjects, show a definite effect of an unrestricted knee-ankle-foot orthosis on gait. PMID- 2251230 TI - Primary Bateman-Leinbach bipolar prosthetic replacement of the hip in the treatment of unstable intertrochanteric fractures in the elderly. AB - The results of primary Bateman-Leinbach bipolar prosthetic replacement for comminuted intertrochanteric fractures of the hip in the elderly are examined. In an effort to avoid the postoperative complications seen in open reduction and internal fixation of severely comminuted fractures with osteoporotic bone, and to avoid postoperative restrictions when fixation is suboptimal, a group of 58 patients were treated with a bipolar Bateman-Leinbach prosthesis. They were followed for an average of 28 months. Surgery was performed using an anterolateral approach, which is recommended. A detailed description of the surgical approach and operative technique are provided. Eighty-eight percent of patients were able to ambulate within the first week, weight bearing as tolerated with no postoperative restrictions, except for a simple abduction pillow for 2 weeks while in bed. Ninety-one percent of patients ambulated prior to discharge. Morbidity and mortality was no greater in this group than in groups treated by open reduction and internal fixation for these types of fractures. Complications were few. Primary Bateman-Leinbach bipolar prosthetic replacement is recommended as the preferred treatment of selected unstable comminuted intertrochanteric fractures in the elderly. PMID- 2251231 TI - Developments in locked femoral nailing. PMID- 2251232 TI - 38-year follow up of femoral endoprosthesis. PMID- 2251233 TI - A subperiosteal abscess of the ilium. PMID- 2251234 TI - Modified Judet radiographic projection in evaluation of acetabular insufficiency secondary to metastatic disease. PMID- 2251235 TI - Posttraumatic Aeromonas hydrophila osteomyelitis. PMID- 2251236 TI - Pseudogout and pseudosepsis of the shoulder. PMID- 2251237 TI - Answer please. Femur fractures associated with total hip arthroplasty. PMID- 2251238 TI - A new medium containing antibiotics for the xenic cultivation of Entamoeba gingivalis. AB - Diamond's trypticase-yeast extract-serum-gastric mucin (TYSGM-9) medium was studied for its suitability to support the xenic growth of the oral protozoan Entamoeba gingivalis. Amoebic growth was found to be best when the inoculum for transfer was 0.1 ml, the incubation temperature was 35 degrees C, and the interval between transfers was 48 h. These parameters were also useful for controlling the growth of accompanying bacteria. In addition, bacterial growth in xenic stock cultures, which had a direct effect on the activity of E. gingivalis trophozoites, was kept to a minimum by addition of the antibiotics piperacillin, erythromycin, neomycin, and penicillin. Varying substitutions and selected supplementations of TYSGM-9 medium led to the development of an improved medium for E. gingivalis. Supplements most beneficial for the growth of E. gingivalis trophozoites were ascorbic acid, ferric ammonium citrate, and special NCTC 107 vitamin mixture. As compared with TYSGM-9 medium (6-10 E. gingivalis trophozoites observed per field), the new E. gingivalis medium supported excellent growth (16 20 E. gingivalis trophozoites observed per field during optimal growth) of the oral protozoan. The medium is suitable for clinical isolation of E. gingivalis. PMID- 2251239 TI - An improved ELISA for the detection of antibodies against Babesia bovis using either a native or a recombinant B. bovis antigen. AB - Two new enzyme-linked immunosorbent assays (ELISA) for the diagnosis of Babesia bovis in cattle are described. The ELISA using a native antigen is more sensitive and less laborious than the assays described previously, because it does not require adsorption of sera with bovine erythrocytes. The second ELISA, using a recombinant B. bovis antigen expressed in Escherichia coli, was both sensitive and specific. It is suitable to replace the native antigen, thus avoiding large batch-to-batch variations in antigen preparations and the need to sacrifice experimental cattle. PMID- 2251240 TI - Lethal efficacy of extract from Zingiber officinale (traditional Chinese medicine) or [6]-shogaol and [6]-gingerol in Anisakis larvae in vitro. AB - The authors previously reported that an extract from Zingiber officinale, traditionally eaten along with raw fish and used in traditional Chinese medicine, effectively destroyed Anisakis larvae in vitro. In this study, we analyzed the effective components of ginger rhizomes. Methanol extracts were fractionated after first being treated with HCl at pH 3, then with NaHCO3 at pH 10, and, finally, with NaOH at pH 13 (fraction 1). In general, this fraction is rich in neutral substances. [6]-Shogaol and [6]-gingerol, known neutral components of ginger rhizomes, were detected using gas chromatography and were found to be the most prevalent components in the fraction, occurring in quantities that resulted in a dose-dependent killing efficacy. Authentic [6]-shogaol and [6]-gingerol could kill Anisakis larvae at a minimal effective dose of 62.5 and 250 micrograms/ml, respectively. However, the concentration of [6]-gingerol in fraction 1 was greater than 20 times that of [6]-shogaol, making the former the most active component in the fraction. Furthermore, synergistic effects between [6]-gingerol and a small amount of [6]-shogaol were observed. Pyrantel pamoate, an available antinematodal drug, had no lethal effect, even at a concentration of 1 mg/ml. In saline solution containing [6]-shogaol (62.5 micrograms/ml), greater than 90% of larvae lost spontaneous movement within 4 h and were destroyed completely within 16 h. Microscopical examinations showed destruction of the digestive tract and disturbances of culticulae. PMID- 2251241 TI - Biochemical characterization, localization and immunostimulating properties of a soluble glycoprotein, Ag1, isolated from in vitro cultures of Plasmodium falciparum. AB - The soluble amphiphilic glycoprotein, Ag1 (gp60), purified from supernatants of in vitro cultures of Plasmodium falciparum has a molecular mass of 60 kDa and did not exhibit size variation in the different P. falciparum isolates tested by immunoblotting. Ag1 was shown to interact with the lectin Erythrina christagalli agglutinin, which is specific for carbohydrates bearing beta-D-galactose(1-4)-D-N acetylglucosamine. Indirect immunofluorescence studies showed that Ag1 is located on the surface of trophozoites and schizonts but not on the surface of merozoites. Ag1 is recognized by human immune sera from six different malaria endemic regions. Ag1 induces in vitro proliferation of lymphocytes from malaria immune individuals in an antigen-specific manner. PMID- 2251242 TI - Purification of the erythrocytic stages of Babesia bigemina from cultures. AB - Exposure of erythrocytes infected with Babesia bigemina to glycerol-enhanced osmotic shock yielded preparations containing infected erythrocyte ghosts, free parasites, and some intact erythrocytes. The released parasites were purified and concentrated by centrifugation in Percoll gradient. Recovered free parasites were shown by the fluorescein acetate technique to be metabolically active, but their infectivity in vitro was low. It was demonstrated by electron microscopy that most of the released parasites had intact plasma membranes. There was only slight contamination of the free-parasite preparation with host erythrocyte debris. PMID- 2251244 TI - Experimental infection of the leaf-monkey, Presbytis cristata, with subperiodic Brugia malayi. AB - Presbytis cristata monkeys infected through the inoculation of between 200 and 400 subperiodic Brugia malayi infective larvae (L3) in the right thigh, in both thighs or in the dorsum of the right foot were followed up for varying periods of up to about 8 months after infection. All 148 inoculated animals became patent, with mean prepatent periods being between 66 and 76 days. In animals injected in the thigh, the patterns of microfilaraemia were similar, there being a rapid rise in the geometric mean counts (GMCs) of microfilariae during the first 10-12 weeks of patency, which then plateaued at levels of greater than 1000/ml. Adult worm recovery, expressed as the percentage of the infective dose, was significantly higher in animals injected with 100 L3 in each thigh, being 9.4% as compared with 2.8%-4.8% in other groups. It is therefore recommended that animals should be injected with 100 L3 in each thigh and that the testing of potential filaricides in this model be carried out during the phase of rapid increase in microfilaraemia to ensure that any microfilaricidal effect can easily be detected. PMID- 2251243 TI - Role of calcium and erythrocyte cytoskeleton phosphorylation in the invasion of Plasmodium falciparum. AB - The role of calcium in the invasion of the human erythrocyte by the parasite Plasmodium falciparum was studied. The intraerythrocytic and intraparasitic concentrations of Ca2+ were modified using calcium-ionophore A23187 and the chelator EGTA. The Ca2+ inside the parasite appeared to be necessary for the normal completion of invasion. We determined that in recently invaded erythrocytes (2 h), the Ca2+ concentration increased about 10 times. Merozoite invasion produced a decrease in beta-spectrin phosphorylation and an increase in the phosphorylation of a protein with band 4.1 mobility. These changes were similar to those produced by an ionophore-mediated Ca2+ influx in uninfected erythrocytes. These facts support the idea that a calcium influx into erythrocytes might precede or accompany merozoite invasion, triggering a series of molecular events, including phosphorylation and dephosphorylation of cystoskeletal proteins. PMID- 2251245 TI - Oogenesis in the free proglottis of Trilocularia acanthiaevulgaris (Cestoda, Tetraphyllidea). AB - The early (ovarian) stages of oogenesis in Trilocularia acanthiaevulgaris have been studied by light microscope histochemistry and transmission electron microscopy. The process proceeds as far as meiotic prophase in the primary oocyte. The oogonia and early immature primary oocytes occupy the anterior and outer edges of the ovary and are typically undifferentiated cells, showing a high nucleo-cytoplasmic ratio. The scant cytoplasm is packed with free ribosomes and contains a small number of mitochondria and a few short strands of granular endoplasmic reticulum (GER). The oogonia undergo a number of mitotic divisions, marked by the presence of centrioles. The immature primary oocytes enter meiotic prophase, as evidenced by the appearance of nuclear synaptonemal complexes. The maturing primary oocytes, which occupy the inner, central region of the ovary, undergo a growth phase that is accompanied by an increased nucleolar volume and export of RNA to the cytoplasm via nuclear pores, and by an increase in the number of mitochondria. A GER network develops and, together with the Golgi complexes, is involved in the production of a small number of cortical granules. The GER often takes the form of concentric cisternae. Numerous lipid droplets are also present in the cytoplasm. The mature primary oocytes predominate in the posterior region of the ovary, near the oviduct. They represent a resting phase in development, in which cellular activity is minimal. Lipid droplets are abundant and the cortical granules remain in more central regions of the cell and do not migrate to the periphery of the cell. The ovary contains a second, non germinal type of cell, the follicle cell. The cell body is smaller in size than the oogonia, and cytoplasmic processes from it ramify around the periphery of the ovary. The different cell types within the ovary are embedded in a cytoplasmic matrix that contains a number of organelles. PMID- 2251246 TI - Transmission electron microscopic studies on the effects of toltrazuril on Glugea anomala, Moniez, 1887 (Microsporidia) infecting the three-spined stickleback Gasterosteus aculeatus. AB - A symmetric triazinone, toltrazuril, was tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in toltrazuril-containing water as intermittent therapy (3 x 2 micrograms/ml for 6 h at 3-day intervals or 3 x 2 micrograms/ml for 24 h at 2-day intervals). As seen at the ultrastructural level, the drug caused severe damage to all developmental stages of G. anomala. When treatment was carried out for 6 h, the xenoma wall exhibited a network appearance. The multinucleate meronts showed tapering at one end and were lysed at places; disintegration of the nuclei was also observed. The sporogonial plasmodia were partially fragmented, and the dumbbell-shaped nuclei of the sporoblast mother cells showed damaged spindle fibres and lysis of the chromosomal material and nuclear membranes. The shape of the mature spores was altered as well. When treatment was done for 24 h, the xenoma wall was completely destroyed. The uni- and multinucleate meronts were completely destroyed and lacked their nuclei, and the sporogonial plasmodia were frequently totally fragmented. The development of the sporophorous vesicle stopped in many cases. In the sporoblasts and their mother cells, vacuolization of the cytoplasma and lysis of the nuclei were observed. Destroyed spores with damaged polar tubes and polaroblasts were frequently detected. It seems likely that toltrazuril could be successfully applied against Microsporidia in fish when used as intermittent therapy at low doses and with prolonged exposure. PMID- 2251247 TI - Experimental transfer of immunity to Plasmodium yoelii nigeriensis from adult rats to baby rats. PMID- 2251248 TI - Radiolabeling of Necator americanus third stage larvae with 75Se-methionine. AB - Third stage larvae of Necator americanus were radiolabeled with 75Se-methionine by two methods. Larvae labeled in aqueous cultures contained 188 and 25 cpm per sheathed and ex-sheathed larva, respectively. Larvae labeled in coproculture incorporated 25 and 18 cpm per sheathed and ex-sheathed larva, respectively. All of the label was decayed in 5 days from larvae labeled in aqueous cultures, whereas appreciable amounts of radioactivity were still detectable at day 7 of chase period in coproculture labeled larvae. PMID- 2251249 TI - Experimental cutaneous leishmaniasis by Leishmania amazonensis: course of fast growth infection in the mouse ear. PMID- 2251250 TI - Characterization of the human 5-lipoxygenase gene promoter. AB - Nucleotide sequences that direct transcription of the human 5-lipoxygenase gene have been examined by ligation to the chloramphenicol acetyltransferase gene and determination of chloramphenicol acetyltransferase activity in transfected HeLa and HL-60 cells. Various lengths of 5'-flanking sequences up to 5.9 kilobase pairs 5' of the transcriptional initiation sites were tested. Two positive and two negative apparent regulatory regions were seen. Part of the promoter sequence (-179 to -56 from ATG), which includes five repeated GC boxes (the putative Sp1 binding sequence) was essential for transcription in both HeLa and HL-60 cells. Gel-shift assays (using the DNA fragment -212 to -88) revealed that the transcriptional factor Sp1 could bind to this region of the 5-lipoxygenase promoter. Furthermore, HL-60 nuclear extracts contained specific nuclear factor(s) binding to 5-lipoxygenase promoter DNA, which could not be detected in HeLa cell nuclear extracts. PMID- 2251251 TI - Molecular phylogeny of Dictyostelium discoideum by protein sequence comparison. AB - Comparison of the amino acid sequences of eight proteins from the soil amoeba Dictyostelium discoideum to those of their homologs in bacteria, yeast, and other eukaryotes indicates that Dictyostelium diverged from the line leading to mammals at about the same time as the plant/animal divergence. Yeast appear to have diverged considerably earlier. It is argued that previous analyses indicating that D. discoideum diverged before yeast were misleading because of the nature of the small ribosomal subunit rRNA sequences used in these studies. We suggest that amino acid sequences may be more reliable than untranslated nucleic acid sequences for evolutionary comparisons, especially among organisms with significant skewing of their A+T content. PMID- 2251252 TI - Extracellular matrix and hormones transcriptionally regulate bovine beta-casein 5' sequences in stably transfected mouse mammary cells. AB - Milk protein regulation involves synergistic action of lactogenic hormones and extracellular matrix (ECM). It is well established that substratum has a dramatic effect on morphology and function of mammary cells. The molecular mechanisms that regulate the ECM- and hormone-dependent gene expression, however, have not been resolved. To address this question, a subpopulation (designated CID 9) of the mouse mammary epithelial cell strain COMMA-1D has been developed in which more than 35% of the cells express beta-casein, form alveoli-like structures when plated onto a reconstituted basement membrane, and secrete beta-casein unidirectionally into a lumen. These cells were stably transfected with a series of chloramphenicol acetyltransferase (CAT) fusion genes to study transcriptional regulation of the bovine beta-casein gene. The expression of CAT in these lines demonstrated a striking matrix and hormone dependency (greater than 150-fold induction in some cases). This regulation occurred primarily at the transcriptional level and was dependent on the length of the 5' flanking region of the beta-casein promotor. Both matrix and hormonal control of transcription occurred within at least the first 1790 base pairs upstream and/or 42 base pairs downstream of the transcriptional initiation site. The ECM effect was independent of glucocorticoid stimulation. However, prolactin was essential and hydrocortisone further increased CAT expression. Endogenous beta-casein expression in these lines was similar to that of the parent CID 9 cells. Our data indicate the existence of matrix-dependent elements that regulate transcription. PMID- 2251253 TI - Alpha and beta replication origins of plasmid R6K show similar distortions of the DNA helix in vivo. AB - Plasmid R6K contains inverted repeats of an approximately 100-base-pair sequence separated by 5.5 kilobases. These long inverted repeats (LIRs) occur within the alpha and beta origins of replication and are essential for origin function. In this study, primer-extension analysis of DNA modified in vivo by dimethyl sulfate or KMnO4 revealed that both alpha and beta LIRs acquire similar structural distortions of the DNA helix in a functional R6K replicon. These distortions were not seen in plasmids containing isolated LIR sequences. In the functional replicon, the dimethyl sulfate and KMnO4 hyperreactive sites appear on complementary strands and are located to one side of an internal palindromic sequence within the LIRs. This asymmetry coincides with the primary direction of DNA replication from alpha and beta origins in vivo. We also observed two intermediate structures when certain R6K cis- or trans-acting elements are missing. Sequences near the alpha origin are required for generation of the dimethyl sulfate hyperreactive sites, whereas sequences near the beta origin are responsible for the appearance of KMnO4 hyperreactive sites. We suggest that these structures represent a hierarchy that leads to a "locked" preinitiation complex, which functions to synchronize and determine the direction of replication from the alpha and beta replication origins in vivo. PMID- 2251254 TI - Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. AB - Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP 1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane spanning (II), spacer (III), alpha-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis. PMID- 2251255 TI - Resolution of hypervariable regions in T-cell receptor beta chains by a modified Wu-Kabat index of amino acid diversity. AB - The Wu-Kabat variability coefficient is a well-established descriptor of the susceptibility of an amino acid position to evolutionary replacements. It conveniently highlights stretches of accentuated amino acid variation that, for example, in an antibody molecule account for most of the antigen contacts (complementarity-determining regions). Diverse opinion are held as to why the index yields unclear results when applied instead to the polypeptide sequences of the T-cell antigen receptor. We show that a simple modification enhances the resolving power of the index by increasing the weight on the frequency distribution of the amino acids in the formula. Application of the improved index to T-cell receptor beta chains highlights four unambiguous hypervariable regions, three of which are positioned similar to immunoglobulin complementarity determining regions along the chain. In a Fab-like three-dimensional model of the T-cell receptor, the four hypervariable regions coincide with the four loops on the surface of the domain and form a contiguous area available for binding. PMID- 2251256 TI - Recombinant yeast TFIID, a general transcription factor, mediates activation by the gene-specific factor USF in a chromatin assembly assay. AB - The TATA box-binding transcription factor TFIID from Saccharomyces cerevisiae was tested for its ability to mediate regulatory factor functions both in a cell-free system reconstituted with other general initiation factors (purified from HeLa cells) and in a combined nucleosome assembly-transcription system. In the latter assay recombinant yeast TFIID, expressed in and purified from bacteria, was sufficient to prevent nucleosome assembly-mediated repression and to mediate transcriptional enhancement of the adenovirus major late promoter by the gene specific activator USF. In contrast, recombinant yeast TFIID was unable to mediate activation by USF in the system reconstituted only with purified general factors. Under the same conditions a partially purified natural yeast TFIID was able to mediate activation by both USF and Sp1 (assayed with the human immunodeficiency virus promoter), but to a lesser extent than observed with a partially purified natural human TFIID. The implications of these findings are discussed with respect to the structure of the yeast and human TATA factors and the possible involvement either of specific TFIID modifications or of coactivators. PMID- 2251257 TI - Factors involved in specific transcription by mammalian RNA polymerase II: identification of general transcription factor TFIIG. AB - We have identified and partially characterized another human general transcription factor, TFIIG. Using a reconstituted in vitro system comprised of purified RNA polymerase II, TFIIB, TFIID, TFIIE, and TFIIF, we found that TFIIG was essential for specific initiation from all class II genes tested. In this system TFIIA could partially replace TFIIG; however, even at saturating concentrations of TFIIA, addition of TFIIG further stimulated transcription. Since the chromatographic properties of TFIIG differed significantly from those of TFIIA, we concluded that TFIIA and TFIIG are distinct but functionally related transcription factors. Heparin challenge assays showed that TFIIG is required for the assembly of a functional preinitiation complex. However, it must act after template commitment by TFIID, since this step did not require, and was unaffected by, either TFIIG or TFIIA. PMID- 2251258 TI - Factors involved in specific transcription by mammalian RNA polymerase II: purification and characterization of general transcription factor TFIIE. AB - Human transcription factor TFIIE, a ubiquitous factor required for transcription initiation by RNA polymerase II, was purified to homogeneity by a combination of conventional and HPLC steps. The purified TFIIE contained equimolar amounts of 57 kDa (TFIIE-alpha) and 34-kDa (TFIIE-beta) polypeptides that were judged to be functional subunits on the basis of their copurification with transcriptional activity and the recovery of activity following renaturation of polypeptides separated by reverse-phase HPLC. TFIIE-alpha had an independent TFIIE activity whereas TFIIE-beta had no activity alone but enhanced the activity of TFIIE alpha. In conjunction with gel filtration studies, which indicated a molecular mass of approximately 180 kDa for the native protein, these results suggested that TFIIE is a heterotetramer containing two alpha and two beta polypeptides. Functional studies with the purified TFIIE demonstrated that it is a general initiation factor, required for all of the genes tested, but it failed to show any DNA-dependent ATPase activity. PMID- 2251259 TI - Cloned yeast and mammalian transcription factor TFIID gene products support basal but not activated metallothionein gene transcription. AB - Transcription factor IID (TFIID), the "TATA binding factor," is thought to play a key role in the regulation of eukaryotic transcriptional initiation. We have studied the role of TFIID in the transcription of the yeast metallothionein gene, which is regulated by the copper-dependent activator protein ACE1. Both basal and induced transcription of the metallothionein gene require TFIID and a functional TATA binding site. Crude human and mouse TFIID fractions, prepared from mammalian cells, respond to stimulation by ACE1. In contrast, human and yeast TFIID proteins expressed from the cloned genes do not respond to ACE1, except in the presence of wheat germ or yeast total cell extracts. These results indicate that the cloned TFIID gene products lack a component(s) or modification(s) that is required for regulated as compared to basal transcription. PMID- 2251261 TI - v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. AB - Experimental carcinogenesis has led to a concept that defines two discrete stages in the development of skin tumors: (i) initiation, which is accomplished by using a mutagen that presumably activates a protooncogene, and (ii) promotion, which is a reversible process brought about most commonly by repeated application of phorbol esters. We have created a transgenic mouse strain that carries the activated v-Ha-ras oncogene fused to the promoter of the mouse embryonic alpha like, zeta-globin gene. Unexpectedly, these animals developed papillomas at areas of epidermal abrasion and, because abrasion can also serve as a tumor-promoting event in mutagen-treated mouse skin, we tested these mice for their ability to respond to phorbol ester application. Within 6 weeks virtually all treated carrier mice had developed multiple papillomas, some of which went on to develop squamous cell carcinomas and, more frequently, underlying sarcomas. We conclude that the oncogene "preinitiates" carrier mice, replacing the initiation/mutagenesis step and immediately sensitizing them to the action of tumor promoters. In addition, treatment of the mice with retinoic acid dramatically delays, reduces, and often completely inhibits the appearance of promoter-induced papillomas. This strain has use in screening tumor promoters and for assessing antitumor and antiproliferative agents. PMID- 2251260 TI - In vitro assembly of infectious nucleocapsids of bacteriophage phi 6: formation of a recombinant double-stranded RNA virus. AB - A system is described for assembling infectious bacteriophage phi 6 nucleocapsids in vitro. Procapsids encoded by cDNA copies of genomic segment L in Escherichia coli were used to package and replicate viral RNA segments. The resulting filled particles were shown to be capable of infecting host cell spheroplasts after incubation with purified nucleocapsid shell protein P8. The infected spheroplasts yielded infectious virions. A modified cDNA-derived RNA segment was inserted into virions by this method. The resulting infectious virions contained the same 4 base-pair deletion as the modified cDNA. These findings support the contention that the preformed procapsids are the "machine" that replicates the phi 6 genome, by showing that the cDNA-derived procapsids are competent to package and replicate RNA properly. PMID- 2251262 TI - Variable patterns of expression of luciferase in transgenic tobacco leaves. AB - A carboxyl-terminally modified firefly luciferase, encoded as a gene fusion to the neomycin phosphotransferase gene (which confers kanamycin resistance), was found to be enzymatically active for both enzymes when expressed in bacteria and in transgenic plants. A military-type starlight vision system was used to conveniently analyze the pattern of gene expression in transgenic tobacco plant leaves. Transgenic tobacco plants which expressed luciferase uniformly in all areas of the leaf, and assays for luciferin, demonstrated that luciferin rapidly penetrates all regions of a tobacco leaf in at least two dimensions. Depending on the test gene structure or, presumably, on the transferred DNA (T-DNA) insertional context, other transgenic plants were obtained that expressed luciferase with a wide range of nonuniform patterns from nominally the same cauliflower mosaic virus 35S promoter. For instance, the veins can be dark, while only the interveinal regions of the leaf lamina glow, or only the small capillary veins glow, or only the major veins glow. Local and/or systemic induction in response to wounding was also demonstrated. PMID- 2251263 TI - Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. AB - Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions. PMID- 2251264 TI - Multisurface method of pattern separation for medical diagnosis applied to breast cytology. AB - Multisurface pattern separation is a mathematical method for distinguishing between elements of two pattern sets. Each element of the pattern sets is comprised of various scalar observations. In this paper, we use the diagnosis of breast cytology to demonstrate the applicability of this method to medical diagnosis and decision making. Each of 11 cytological characteristics of breast fine-needle aspirates reported to differ between benign and malignant samples was graded 1 to 10 at the time of sample collection. Nine characteristics were found to differ significantly between benign and malignant samples. Mathematically, these values for each sample were represented by a point in a nine-dimensional space of real variables. Benign points were separated from malignant ones by planes determined by linear programming. Correct separation was accomplished in 369 of 370 samples (201 benign and 169 malignant). In the one misclassified malignant case, the fine-needle aspirate cytology was so definitely benign and the cytology of the excised cancer so definitely malignant that we believe the tumor was missed on aspiration. Our mathematical method is applicable to other medical diagnostic and decision-making problems. PMID- 2251265 TI - Embryonic stem cell virus, a recombinant murine retrovirus with expression in embryonic stem cells. AB - The expression of Moloney murine leukemia virus and vectors derived from it is restricted in undifferentiated mouse embryonal carcinoma and embryonal stem (ES) cells. We have developed a retroviral vector, the murine embryonic stem cell virus (MESV), that is active in embryonal carcinoma and ES cells. MESV was derived from a retroviral mutant [PCC4-cell-passaged myeloproliferative sarcoma virus (PCMV)] expressed in embryonal carcinoma cells but not in ES cells. The enhancer region of PCMV was shown to be functional in both cell types, but sequences within the 5' untranslated region of PCMV were found to restrict viral expression in ES cells. Replacement of this region by related sequences obtained from the dl-587rev retrovirus results in MESV, a modified PCMV virus that confers G418 resistance to fibroblasts and ES cells with similar efficiencies. Expression of MESV in ES cells is mediated by transcriptional regulatory elements within the 5' long terminal repeat of the viral genome. PMID- 2251266 TI - Fuel selection in rufous hummingbirds: ecological implications of metabolic biochemistry. AB - Hummingbirds in flight display the highest rates of aerobic metabolism known among vertebrates. Their flight muscles possess sufficient maximal activities of hexokinase and carnitine palmitoyltransferase to allow the exclusive use of either glucose or long-chain fatty acids as metabolic fuels during flight. Respiratory quotients (RQ = VCO2/VO2) indicate that fatty acid oxidation serves as the primary energy source in fasted resting birds, while subsequent foraging occurs with a rapid shift towards the use of carbohydrate as the metabolic fuel. We suggest that hummingbirds building up fat deposits in preparation for migration behave as carbohydrate maximizers (or fat minimizers) with respect to the metabolic fuels selected to power foraging flight. PMID- 2251267 TI - mutA and mutC: two mutator loci in Escherichia coli that stimulate transversions. AB - Two transversion-specific mutator loci, mutA and mutC, were identified in Escherichia coli. Mutators with high rates of A.T----T.A transversions were identified using a screening technique that relied upon the reversion of an altered lacZ gene back to wild-type via a specific A.T----T.A transversion. Among the mutators collected, one class mapped to a previously unidentified locus that we designate mutA. Analysis of reverse mutations in lacZ and forward nonsense mutations in lacI showed that the mutA strain has higher levels of A.T----T.A and G.C----T.A transversions, and to a lesser degree A.T----C.G transversions. The mutA locus maps very near to, but is separable from, mutL, at about 95 min on the E. coli chromosome. Both its mutagenic specificity and complementation experiments confirmed that mutA is distinct from mutL and from a nearby mutator locus, miaA. The phenotype of a mutA mutL double mutator strain suggests that the mutA gene product prevents some replication errors. Another mutator, designated mutC, maps very near uvrC, at 42 min, but is distinguishable from uvrC, which has no mutator effects. The specificity of reversion of lacZ mutations in a mutC strain is identical to that in a mutA strain. Also, the behavior of a mutC mutS double mutant is identical to that of a mutA mutL double mutant. It is likely that mutA and mutC are components of the same error-avoidance system. PMID- 2251268 TI - Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency. AB - Deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a common inherited defect in energy metabolism. Characterization of the mRNA encoding MCAD in a Dutch MCAD-deficient patient revealed an A----G change at nucleotide position 985 of the MCAD mRNA coding region. This point mutation results in the substitution of a glutamic acid for a lysine at amino acid position 304 of the mature protein. The single base change was not found in any wild-type MCAD mRNAs. A mutant allele specific oligonucleotide probe was used in a hybridization analysis of amplified genomic DNA of MCAD-deficient family members, a carrier, and normal individuals. The hybridization analysis specifically identified individuals who were heterozygotes or homozygotes. In addition to the point mutation, a significant proportion of the index patient's MCAD mRNA contained a variety of deletions and insertions as a result of exon skipping and intron retention. The missplicing occurred in multiple regions throughout the MCAD mRNA. Analysis of the patient's MCAD gene in the regions where the missplicing occurred most frequently did not reveal a mutation in the splicing acceptor or donor sites. Therefore, the molecular characterization of this family revealed a crucial point mutation in the MCAD gene and an unusual abnormality in MCAD pre-mRNA splicing. PMID- 2251269 TI - Modulation of function and gated learning in a network memory. AB - Memory and learning are studied in a model neural network made from component cells with a variety of realistic intrinsic dynamic behaviors. Modulation of intrinsic cellular characteristics causes a network to switch between two entirely different modes of operation. In one mode the network acts as a selective, long-term associative memory, whereas in the other it is a nonselective, short-term latching memory. Such functional modulation can be used as a mechanism for initiating and terminating learning in a network associative memory. PMID- 2251270 TI - Nucleotides that determine Escherichia coli tRNA(Arg) and tRNA(Lys) acceptor identities revealed by analyses of mutant opal and amber suppressor tRNAs. AB - We have constructed an opal suppressor system in Escherichia coli to complement an existing amber suppressor system to study the structural basis of tRNA acceptor identity, particularly the role of middle anticodon nucleotide at position 35. The opal suppressor tRNA contains a UCA anticodon and the mRNA of the suppressed protein (which is easily purified and sequenced) contains a UGA nonsense triplet. Opal suppressor tRNAs of two tRNA(Arg) isoacceptor sequences each gave arginine in the suppressed protein, while the corresponding amber suppressors with U35 in their CUA anticodons each gave arginine plus a second amino acid in the suppressed protein. Since C35 but not U35 is present in the anticodon of wild-type tRNA(Arg) molecules, while the first anticodon position contains either C34 or U34, these results establish that C35 contributes to tRNA(Arg) acceptor identity. Initial characterizations of opal suppressor tRNA(Arg) mutants by suppression efficiency measurements suggest that the fourth nucleotide from the 3' end of tRNA(Arg) (A73 or G73 in different isoacceptors) also contributes to tRNA(Arg) acceptor identity. Wild-type and mutant versions of opal and amber tRNA(Lys) suppressors were examined, revealing that U35 and A73 are important determinants of tRNA(Lys) acceptor identity. Several possibilities are discussed for the general significance of having tRNA acceptor identity in the same positions in different tRNA acceptor types, as exemplified by positions 35 and 73 in tRNA(Arg) and tRNA(Lys). PMID- 2251271 TI - An antifreeze glycopeptide gene from the antarctic cod Notothenia coriiceps neglecta encodes a polyprotein of high peptide copy number. AB - The antarctic fish Notothenia coriiceps neglecta synthesizes eight antifreeze glycopeptides (AFGP 1-8; Mr 2600-34,000) to avoid freezing in its ice-laden freezing habitat. We report here the sequence of one of its AFGP genes. The structural gene contains 46 tandemly repeated segments, each encoding one AFGP peptide plus a 3-amino acid spacer. Most of the repeats (44/46) code for peptides of AFGP 8; the remaining 2 code for peptides of AFGP 7. At least 2 of the 3 amino acids in the spacers could act as substrate for chymotrypsin-like proteases. The nucleotide sequence between the translation initiation codon (ATG) and the first AFGP-coding segment is G + T-rich and encodes a presumptive 37-residue signal peptide of unusual sequence. Primer extension establishes the transcription start site at nucleotide 43 upstream from ATG. CAAT and TATA boxes begin at nucleotides 53 and 49, respectively, upstream from the transcription start site. The polyadenylylation signal, AATAAA, is located approximately 240 nucleotides downstream from the termination codon. A mRNA (approximately 3 kilobases) was found that matches the size of this AFGP gene. Thus, this AFGP gene encodes a secreted, high-copy-number polyprotein that is processed posttranslationally to produce active AFGPs. PMID- 2251272 TI - Multiple stores of calcium are released in the sea urchin egg during fertilization. AB - Fertilization initiates a transient increase in intracellular Ca2+ principally by Ca2+ release from intracellular stores. Possible multiple Ca2+ stores and multiple receptor regulation of the same store have been reported. Here we report the presence of at least two independent intracellular Ca2+ stores in the sea urchin egg, which are released during fertilization. Ca2+ release from one store is mediated by inositol 1,4,5-trisphosphate (IP3) and is sensitive to low molecular weight heparin. The other store is heparin insensitive and independent of IP3 regulation, but the regulatory factor remains unidentified. A transient increase in Ca2+ in heparin-loaded eggs is observed during fertilization, which suggests that IP3-independent Ca2+ release mediates the production of IP3 and release of the IP3-dependent store. Experiments presented here do not support the idea of sperm receptor coupling to inositol phospholipid hydrolysis through a GTP binding protein mediating the fertilization response. PMID- 2251273 TI - Transformed and nontransformed cells differ in stability and cell cycle regulation of a binding activity to the murine thymidine kinase promoter. AB - A DNA binding activity to an upstream region of the murine thymidine kinase gene is regulated differently in a transformed and nontransformed cell line pair. Differences in regulation were observed (i) after serum levels were reduced, (ii) when serum levels were returned to initial high levels, and (iii) while protein synthesis was inhibited. After reduction of serum levels, the binding activity was unstable in nontransformed BALB/c 3T3 clone A31 cells but was significantly more stable in benzo[a]pyrene-transformed BALB/c 3T3 cells. After serum concentration was returned to high levels, the kinetic pattern of the binding activity differed between nontransformed and transformed cells. While protein synthesis was inhibited, the binding activity was unstable in nontransformed cells and stable in transformed cells. Partial inhibition of protein synthesis--a more stringent condition to test instability--prevented the induction of the binding activity in nontransformed cells. Previously, the labile protein hypothesis set forth the criterion that a protein regulating the onset of DNA synthesis should be unstable in nontransformed cells and stable in transformed cells. The DNA binding activity described here satisfies this criterion. PMID- 2251275 TI - Control of mitochondrial gene expression in the yeast Saccharomyces cerevisiae. AB - Mitochondrial promoters in Saccharomyces cerevisiae contain an identical octanucleotide [sequence: see text] sequence present just upstream of the initiation site (at the left end of the arrow). Studies have shown that the transcription rates of mitochondrial genes vary from 7- to 15-fold. The nucleotide at position +2 regulates the efficiency of mitochondrial promoters but does not affect the specificity of initiation. The data presented herein demonstrate that the variable transcription rates of mitochondrial genes are due to different levels of transcriptional initiation. The rate of first phosphodiester bond formation between a purine and a pyrimidine on a weak promoter is much lower than that of purine-purine on a strong promoter. A dinucleotide corresponding to positions +1 and +2 acts in vitro as a primer, bypassing the first phosphodiester bond formation at the initiation site. When these dinucleotides were used to prime transcription, the activities of the strong and weak promoters were found to be identical. In heparin-challenge experiments, there is no significant effect of dinucleotide on heparin-resistant DNA-RNA polymerase complex formation. These results indicate that the low level of transcription from the weak mitochondrial promoter is due to the slow rate of formation of the first phosphodiester bond. PMID- 2251274 TI - Evidence against a requisite role for defective virus in the establishment of persistent hepadnavirus infections. AB - The factors involved in the establishment of persistent hepadnavirus infection are poorly understood. Recent findings demonstrate that the sequence of the genome of hepatitis B virus (HBV) is variable in infected individuals and that, in some cases, virus mutants predominate. Our objectives in the present study were to analyze the variability of woodchuck hepatitis virus (WHV) genomes in an infected animal and to determine whether sequence heterogeneity played a critical role in the ability of WHV to induce chronic infection. We cloned and determined the complete nucleotide sequence of three supercoiled genomes from an animal that became infected after inoculation with a standardized WHV serum pool (i.e., the WHV7 virus pool). We found that there were four nucleotide substitutions among the three genome sequences as well as a 73-nucleotide deletion in one of the recombinants. DNA transfection experiments revealed that only one of the three recombinants was capable of independent replication. These data suggest that a significant proportion of replicative templates in woodchucks that are infected with WHV are defective virus genomes. Next, we compared the outcome of acute infection after inoculation with a serum pool containing a uniform population of replication competent virus (i.e., the WHV7R pool) with a serum pool composed of WHV genomes of variable sequence. The WHV7R serum pool originated from a woodchuck that became a chronic carrier after in vivo transfection of the liver with the infectious WHV7 recombinant. Neonatal woodchucks were inoculated with 5 x 10(6) WHV genome equivalents of either the WHV7 pool or the WHV7R pool. All animals in the study became acutely infected with WHV. Of the animals infected with the WHV7 serum pool, 65% became chronic carriers, while 80% of the animals infected with the WHV7R serum pool developed chronic infection. Thus, infection of woodchucks with a serum pool containing defective virus resulted in a rate of chronic WHV infection that was similar to, or even lower than, a rate from a pool containing only wild-type virus. This suggests that the presence of defective virus in the inoculum is not a prerequisite for the establishment of persistent hepadnavirus infections. PMID- 2251276 TI - Thickness determination of biological samples with a zeta-calibrated scanning tunneling microscope. AB - A single-tube scanning tunneling microscope has been zeta-calibrated by using atomic steps of crystalline gold and was used for measuring the thickness of two biological samples, metal-coated as well as uncoated. The hexagonal surface layer of the bacterium Deinococcus radiodurans with an open network-type structure shows thickness values that are strongly influenced by the substrate and the preparation method. In contrast, the thickness of the purple membrane of Halobacterium halobium with its densely packed less-corrugated structure exhibits very little variation in thickness in coated preparations and the values obtained are in good agreement with x-ray data. PMID- 2251277 TI - Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. AB - Translocations involving chromosome 11, band q23, are frequent recurring abnormalities in human acute lymphoblastic and acute myeloid leukemia. We used 19 biotin-labeled probes derived from genes and anonymous cosmids for hybridization to metaphase chromosomes from leukemia cells that contained four translocations involving band 11q23: t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13). The location of the cosmid probes relative to the breakpoint in 11q23 was the same in all translocations. Of the cosmid clones containing known genes, CD3D was proximal and PBGD, THY1, SRPR, and ETS1 were distal to the breakpoint on 11q23. Hybridization of genomic DNA from a yeast clone containing yeast artificial chromosomes (YACs), that carry 320 kilobases (kb) of human DNA including CD3D and CD3G genes, showed that the YACs were split in all four translocations. These results indicate that the breakpoint at 11q23 in each of these translocations occurs within the 320 kb encompassed by these YACs; whether the breakpoint within the YACs is precisely the same in the different translocations is presently unknown. PMID- 2251278 TI - Direction selectivity of blowfly motion-sensitive neurons is computed in a two stage process. AB - Direction selectivity of motion-sensitive neurons is generally thought to result from the nonlinear interaction between the signals derived from adjacent image points. Modeling of motion-sensitive networks, however, reveals that such elements may still respond to motion in a rather poor directionally selective way. Direction selectivity can be significantly enhanced if the nonlinear interaction is followed by another processing stage in which the signals of elements with opposite preferred directions are subtracted from each other. Our electrophysiological experiments in the fly visual system suggest that here direction selectivity is acquired in such a two-stage process. PMID- 2251279 TI - Mitochondrial respiratory inhibition by N-methylated beta-carboline derivatives structurally resembling N-methyl-4-phenylpyridine. AB - Mitochondrial accumulation and respiratory inhibition are critical steps in the actions of N-methyl-4-phenylpyridinium ion (MPP+), the toxic metabolite of the parkinsonism-inducing agent, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We examined the respiratory characteristics of 2-methylated beta-carbolines (2-Me beta Cs) and 2-methylated 3,4-dihydro-beta-carbolines (2-MeDH beta Cs), which encompass the MPP+ structure. As indoleamine derivatives, they could have endogenous roles in idiopathic parkinsonism. With rat liver mitochondria, the order for inhibition of NAD(+)-linked O2 consumption (6-min preincubations) was as follows: MPP+ = 2-methylharmine greater than 2-methylharmol = 2 methylharmaline much greater than 2-methylharmalol greater than 2-methylnorharman greater than 6-OH-2-methylharmalan much greater than 2-methylharman. Similar to MPP+, 2-MeDH beta C/2-Me beta C inhibition was potentiated by tetraphenylboron and reversed by dinitrophenol, consistent with the involvement of cationic forms. However, the participation of neutral forms was indicated by the 2-MeDH beta C/2 Me beta C inhibitory time courses, which were unlike MPP+. The neutral forms probably arise via indolic nitrogen deprotonation because the characteristics of a cationic beta-carboline that cannot N-deprotonate, 2,9-dimethylnorharman, mirrored MPP+ rather than 2-Me beta Cs. Succinate-supported respiration was also significantly blocked by 2-MeDH beta Cs/2-Me beta Cs, but results with tetraphenylboron and 2,9-dimethylnorharman indicated that cationic forms were less important than in the inhibition of NAD(+)-linked respiration. We suggest that the relatively potent inhibition by certain 2-MeDH beta Cs/2-Me beta Cs involves neutral forms for passive mitochondrial entry and cationic as well as neutral forms that act at several respiratory sites. Respiratory inhibition could reasonably underlie the reported neurotoxicity of 2-Me beta Cs. PMID- 2251281 TI - p-Aminobenzoate synthesis in Escherichia coli: purification and characterization of PabB as aminodeoxychorismate synthase and enzyme X as aminodeoxychorismate lyase. AB - The Escherichia coli pabA and pabB genes have been overexpressed separately and in tandem. Using purified PabB, we have confirmed the recent suggestion that PabB needs an additional protein, enzyme X, to convert chorismate and NH3 to p aminobenzoate (PABA). With chorismate and NH3, pure PabB generates an intermediate presumed to be 4-amino-4-deoxychorismate based upon UV/visible spectroscopy and enzymatic and nonenzymatic transformations. The PabB-catalyzed interconversion of chorismate and isolated aminodeoxychorismate is readily reversible. With pure PabB as a stoichiometric assay reagent, enzyme X was purified approximately 800-fold to near homogeneity as an apparent homodimer of 50 kDa from E. coli. Enzyme X shows no activity on chorismate but quantitatively converts the preformed aminodeoxychorismate into p-aminobenzoate and pyruvate, acting thereby as an aminodeoxychorismate lyase. PMID- 2251280 TI - Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. AB - Intracellular proteolytic processing of precursor polypeptides is an essential step in the maturation of many proteins, including plasma proteins, hormones, neuropeptides, and growth factors. Most frequently, propeptide cleavage occurs after paired basic amino acid residues. To date, no mammalian propeptide processing enzyme with such specificity has been purified or cloned and functionally characterized. We report the isolation and functional expression of a cDNA encoding a propeptide-cleaving enzyme from a human liver cell line. The encoded protein, called PACE (paired basic amino acid cleaving enzyme), has structural homology to the well-characterized subtilisin-like protease Kex2 from yeast. The functional specificity of PACE for mediating propeptide cleavage at paired basic amino acid residues was demonstrated by the enhancement of propeptide processing of human von Willebrand factor when coexpressed with PACE in COS-1 cells. PMID- 2251282 TI - Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen. AB - Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ2, and delta 12 PGJ2, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA2 and delta 12 PGJ2 in primary cultures of purified rat hepatocytes. As a model ligand, [3H]PGA1 bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 microM (low affinity). The high-affinity binding of [3H]PGA1 was 9- and approximately 13-fold more avid than the binding of the conventional fatty acid ligands, oleic acid and arachidonic acid, respectively. The abilities of different prostaglandins to compete with the high-affinity binding of [3H]PGA1 correlated with their growth inhibitory activities reported previously and here. The growth inhibitory cyclopentenone prostaglandins (PGA1, PGA2, delta 12-PGJ2, and PGJ2) were the best competitive ligands, intermediate competitors were the weak growth inhibitors PGE1 and PGD2, and the poorest competitors were PGE2 and PGF2 alpha, which stimulate rather than inhibit DNA synthesis in rat hepatocytes in primary culture. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins. PMID- 2251283 TI - Expression and chromosomal localization of a lymphocyte K+ channel gene. AB - We recently isolated a family of three closely related mouse K+ channel genes (MK1, MK2, and MK3) with coding regions contained in single uninterrupted exons. Here we have used patch-clamp recordings from Xenopus oocytes injected with mRNA to show that MK3 encodes a channel with biophysical and pharmacological properties indistinguishable from those of voltage-gated type n K+ channels in T cells. In addition, we used the polymerase chain reaction to demonstrate the presence of MK3 mRNA in T cells. These data suggest that MK3 may encode the T cell voltage-gated type n K+ channel. We also show that MK3 and MK2 are localized on human chromosomes 13 and 12, respectively. PMID- 2251284 TI - Lipophilic halogenated congeners of 2',3'-dideoxypurine nucleosides active against human immunodeficiency virus in vitro. AB - Four 2-amino-6-halo- and four 6-halo-2',3'-dideoxypurine ribofuranosides (ddPs) were synthesized and tested for in vitro activity to suppress the infectivity, cytopathic effect, Gag protein expression, and DNA synthesis of human immunodeficiency virus (HIV). The comparative order of in vitro anti-HIV activity of the eight 6-halo-ddPs was as follows: 2-amino-6-fluoro, 2-amino-6-chloro, 6 fluoro greater than 2-amino-6-bromo greater than 2-amino-6-iodo, 6-chloro greater than 6-bromo greater than 6-iodo. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6 fluoro-ddPs showed a potent activity against HIV comparable to that of 2',3' dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG) and completely blocked the infectivity of HIV without affecting the growth of target cells. The lipophilicity order was as follows: 2-amino-6-iodo greater than 2-amino-6-bromo greater than 2-amino-6-chloro greater than 2-amino-6-fluoro much greater than ddG greater than ddI. All eight 6-halo-ddPs were substrates for adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4). The relative rates of hydrolysis by ADA were as follows: ddA, 2-amino-6-fluoro much greater than 2-amino-6-chloro, 2 amino-6-bromo greater than 2-amino-6-iodo. Taken together, these compounds may represent an additional class of lipophilic prodrugs for ddI and ddG and may also provide a strategy for endowing therapeutic purine nucleosides with desirable lipophilicity. PMID- 2251285 TI - Thermodynamic characterization of the stability and the melting behavior of a DNA triplex: a spectroscopic and calorimetric study. AB - We report a complete thermodynamic characterization of the stability and the melting behavior of an oligomeric DNA triplex. The triplex chosen for study forms by way of major-groove Hoogsteen association of an all-pyrimidine 15-mer single strand (termed y15) with a Watson-Crick 21-mer duplex composed of one purine-rich strand (termed u21) and one pyrimidine-rich strand (termed y21). We find that the near-UV CD spectrum of the triplex can be duplicated by the addition of the B like CD spectrum of the isolated 21-mer duplex and the CD spectrum of the 15-mer single strand. Spectroscopic and calorimetric measurements show that the triplex (y15.u21.y21) melts by two well-resolved sequential transitions. The first transition (melting temperature, Tm, approximately 30 degrees C) is pH-dependent and involves the thermal expulsion of the 15-mer strand to form the free duplex u21.y21 and the free single strand y15. The second transition (Tm approximately 65 degrees C) is pH-independent between pH 6 and 7 and reflects the thermal disruption of the u21.y21 Watson-Crick duplex to form the component single strands. The thermal stability of the y15.u21.y21 triplex increases with increasing Na+ concentration but is nearly independent of DNA strand concentration. Differential scanning calorimetric measurements at pH 6.5 show the triplex to be enthalpically stabilized by only 2.0 +/- 0.1 kcal/mol of base triplets (1 cal = 4.184 J), whereas the duplex is stabilized by 6.3 +/- 0.3 kcal/mol of base pairs. From the calorimetric data, we calculate that at 25 degrees C the y15.u21.y21 triplex is stabilized by a free energy of only 1.3 +/- 0.1 kcal/mol relative to its component u21.y21 duplex and y15 single strand, whereas the 21-mer duplex is stabilized by a free energy of 17.2 +/- 1.2 kcal/mol relative to its component single strands. The y15 single strand modified by methylation of cytosine at the C-5 position forms a triplex with the u21.y21 duplex, which exhibits enhanced thermal stability. The spectroscopic and calorimetric data reported here provide a quantitative measure of the influence of salt, temperature, pH, strand concentration, and base modification on the stability and the melting behavior of a DNA triplex. Such information should prove useful in designing third-strand oligonucleotides and in defining solution conditions for the effective use of triplex structure formation as a tool for modulating biochemical events. PMID- 2251286 TI - Localization of androgen receptors and estrogen receptors in the same cells of the songbird brain. AB - Estrogens and androgens each have unique effects but act together for the neural differentiation and control of sexual behaviors in male vertebrates, such as the canary. The neuronal basis for these synergistic effects is elusive because the spatial relation between estrogen target cells and androgen target cells is unknown. This study localized estrogen receptor (ER)-containing cells by using immunocytochemistry and androgen receptor (AR)-containing cells by using autoradiography in the same sections of the male canary brain. Three cell types, those containing only ER, those containing only AR, and those containing both ER and AR, were found in tissue-specific frequencies. The midbrain nucleus intercollicularis exhibited the highest number of cells expressing both ER and AR, whereas ER and AR are expressed only in disjunctive cell populations in the forebrain nucleus hyperstriatalis ventrale, pars caudale. Synergistic effects of androgens and estrogens for the neural behavorial control could result from cells containing both ER and AR (intracellular) and from neural circuits containing ER and AR in different cells (intercellular). PMID- 2251287 TI - Oscillations and chaos in neural networks: an exactly solvable model. AB - We consider a randomly diluted higher-order network with noise, consisting of McCulloch-Pitts neurons that interact by Hebbian-type connections. For this model, exact dynamical equations are derived and solved for both parallel and random sequential updating algorithms. For parallel dynamics, we find a rich spectrum of different behaviors including static retrieving and oscillatory and chaotic phenomena in different parts of the parameter space. The bifurcation parameters include first- and second-order neuronal interaction coefficients and a rescaled noise level, which represents the combined effects of the random synaptic dilution, interference between stored patterns, and additional background noise. We show that a marked difference in terms of the occurrence of oscillations or chaos exists between neural networks with parallel and random sequential dynamics. PMID- 2251288 TI - Amplification of an ancestral mammalian L1 family of long interspersed repeated DNA occurred just before the murine radiation. AB - Each mammalian genus examined so far contains 50,000-100,000 members of an L1 (LINE 1) family of long interspersed repeated DNA elements. Current knowledge on the evolution of L1 families presents a paradox because, although L1 families have been in mammalian genomes since before the mammalian radiation approximately 80 million years ago, most members of the L1 families are only a few million years old. Accordingly it has been suggested either that the extensive amplification that characterizes present-day L1 families did not occur in the past or that old members were removed as new ones were generated. However, we show here that an ancestral rodent L1 family was extensively amplified approximately 10 million years ago and that the relics (approximately 60,000 copies) of this amplification have persisted in modern murine genomes (Old World rats and mice). This amplification occurred just before the divergence of modern murine genera from their common ancestor and identifies the murine node in the lineage of modern muroid rodents. Our results suggest that repeated amplification of L1 elements is a feature of the evolution of mammalian genomes and that ancestral amplification events could provide a useful tool for determining mammalian lineages. PMID- 2251289 TI - A recombinant single-chain immunotoxin composed of anti-Tac variable regions and a truncated diphtheria toxin. AB - To kill human or primate cells expressing the p55 subunit of the interleukin 2 receptor, we have constructed a single-chain immunotoxin. DNA sequences encoding the first 388 amino acids of diphtheria toxin (DT) were fused to DNA elements encoding the antigen-binding portion (variable region or Fv) of the anti-Tac monoclonal antibody. The antigen-binding portion consists of 116 amino acids of the heavy-chain variable region connected by a 15-amino acid linker to 106 amino acids of the variable region of the light chain. The single-chain immunotoxin DT388-anti-Tac(Fv) was expressed in Escherichia coli and found in inclusion bodies. The monomeric form was then purified to near homogeneity with a high yield (3-5 mg/liter). Monomeric DT388-anti-Tac(Fv) was highly cytotoxic to cell lines bearing the p55 subunit of the human interleukin 2 receptor but not to cells without this subunit. DT388-anti-Tac(Fv) was also very effective in killing proliferating human T cells produced in a mixed leukocyte reaction. PMID- 2251290 TI - Effects of glycyl-L-glutamine and methylprednisolone on maintenance of acetylcholinesterase of transected rat sciatic nerves. AB - Under anesthesia with sodium pentobarbital, the sciatic nerves of rats were transected bilaterally, and a catheter was inserted into the central end of the left renal artery. After an initial flush, an Alzet pump was attached to the catheter, containing various concentrations of glycyl-L-glutamine (Gly-Gln), methylprednisolone sodium succinate (MePred), or both. Rats were sacrificed at intervals of 2, 4, or 6 days; the peripheral portions of the sciatic nerves were excised, homogenized, and centrifuged, and the supernates were assayed for acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) and protein. Significantly higher contents of AcChoEase over untreated transected controls were obtained (i) at 4 days posttransection in rats infused with 0.015 M Gly-Gln and (ii) at 6 days posttransection in rats infused with MePred at 3.0 mg.kg-1.hr-1 after an initial dose of 120 mg/kg with or without Gly-Gln. PMID- 2251292 TI - Influence of ova within rat oviducts on spontaneous motility and on prostaglandin production. AB - The present study was performed in order to explore the influence of ova present within rat oviducts on: a) tubal spontaneous motility and b) oviduct prostaglandin production. It was found that the isometric developed tension (IDT) of tubes isolated from proestrous rats (preovulatory oviducts) was significantly higher (P less than 0.01) than the IDT of tubes from rats at estrus and at metestrus (postovulatory oviducts). After flushing the oviducts with KRB solution (i.e., after removing existing ova) the IDT of the oviducts obtained from estrous rats increased significantly (P less than 0.01), whereas the IDT of tubes isolated from proestrous rats (i.e., preparations without ova) was not modified. On the other hand, isolated tubes containing their corresponding ova released into the suspending solution significantly more PGE1 than PGE2 or PGF2 alpha (P less than 0.005). It was particularly interesting to find that after flushing the oviducts, tissue production of PGE1, PGE2 and PGF2 alpha was similar. Finally, when dose response curves for PGE1 and for PGE2 on the spontaneous contractions of oviducts isolated from rats at proestrus, estrus and metestrus were constructed, both PGs evoked an inhibitory inotropic action. The ED50 for PGE1 in tubes from estrous rats was significantly smaller (P less than 0.01) than that for metestrous animals but significantly greater (P less than 0.01) than that observed in oviducts from proestrous rats. The ED50 for PGE2 did not change in the different tested periods of the sex cycle. Results reported herein suggest the possibility that the ova present within rat oviducts, may influence their own transport along the tubes by modifying the amount of prostaglandins produced by the oviducts or via their own prostaglandin synthesis. PMID- 2251291 TI - Vaccination against tumor cells expressing breast cancer epithelial tumor antigen. AB - Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts. PMID- 2251293 TI - Isolation of rat renal NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. AB - Rat renal NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase was purified to apparent homogeneity in the present study. The purification included ammonium sulfate precipitation, DEAE-Sepharose CL-6B column chromatography, Blue Sepharose CL-6B column chromatography, Sephadex G-100 column chromatography and Mono-P isoelectrofocusing column chromatography. Among the chromatographies used, Mono-P chromatofocusing column of fast protein liquid chromatography gave the most powerful resolution. The enzyme was eluted at pH 6.75 on chromatofocusing column. It indicated that the rat renal enzyme is an acidic protein. Its molecular weight in SDS-polyacrylamide gel electrophoresis was 28 Kd, and the molecular weight of the enzyme having enzyme activity detected by gel filtration column chromatography was 55 Kd. For comparing the characteristics of rat renal enzyme with that of human placental enzyme, polyclonal antibodies and a monoclonal antibody against human placental enzyme were used. The rat renal enzyme did not react with the polyclonal antibodies of human placental enzyme, however, it reacted with a monoclonal antibody of human placental enzyme. The results indicated that the antigenicity of rat renal NAD(+)-dependent 15 hydroxyprostaglandin dehydrogenase is different from that of human placental enzyme. The amino acid composition of rat renal enzyme was also different from that of human placental enzyme. Nine tyrosine molecules were observed in the subunit of rat renal enzyme, while no tyrosine has been reported in human placental enzyme. PMID- 2251294 TI - Prostaglandin biosynthesis by human decidual cells: effects of inflammatory mediators. AB - There is substantial evidence that decidual activation, in association with infection, is linked with the onset of both preterm and term labor. We therefore undertook the present study to evaluate prostaglandin production and its potential regulation by inflammatory mediators in human decidual cells in primary monolayer culture. Upon attaining confluence, the cells were incubated with endotoxin, interleukin 1 alpha (IL1 alpha), interleukin 1 beta (IL1 beta); or tumor necrosis factor (TNF). Production of prostaglandin (PG) E2 and PGF2 alpha was determined using specific radioimmunoassays. Endotoxin and these cytokines all induced significant concentration-dependent increases in PGE2 and PGF2 alpha production. Our results suggest that term human decidual cells are responsive to endotoxin and cytokines and that generation of these substances in the decidua or nearby (eg. in response to infection) will lead to increased prostaglandin production and uterine contractions. PMID- 2251295 TI - Changes of 6-keto PGF1 alpha concentration in plasma and vessel wall and TxB2 in plasma of whole-body irradiated rats in the early stage of irradiation. AB - The aim of this work was to monitor concentrations of prostanoids affecting platelet aggregation, namely prostacyclin and thromboxane A2, in the plasma and prostacyclin in the endothelium of vessel wall after whole-body irradiation of rats by the doses 5, 10, 50, 100 and 250 Gy (source 60Co) in the early stage of irradiation up to 24 hours. Stable metabolites of the prostanoids - 6-keto PGF1 alpha and TxB2 were determined by a RIA technique. The 6-keto PGF1 alpha plasma concentration increased after irradiation by the 50 Gy dose between 3rd and 24th hours and at all sampling times after the 100 and 250 Gy doses. A rise in prostanoid concentrations was noted after low doses of irradiation in the first sampling intervals only. The TxB2 level increased after the same doses (5 and 10 Gy) up to the 6th hour and then decreased. The thromboxane concentration increased after 50 Gy at the 90th minute, 12th and 24th hours, after 100 Gy at the 24th hour and after 250 Gy at the 90th minute, 3rd and 24th hours. PMID- 2251296 TI - Cardiodynamic improvement following PGE1 administration in sheep with congestive heart failure. AB - The cardiodynamic effects of Prostaglandin E1 were studied in sheep with congestive heart failure. Six Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, [+dP/dt]max and a single exponential time constant (T) were calculated on a computer from the recorded pressure curves and the Wilcoxon signed rank test used to determine the statistical significance of the differences. Prostaglandin E1 (20 micrograms.kg 1) significantly improved left ventricular contractility and relaxation rate as seen respectively from [+dP/dt]max and the single-exponential time-constant and reduced the afterload conditions under which the heart operated, during various stages of congestive heat failure, without significant tachycardia during the more advanced stages of the disease. The results show that [+dP/dt]max increased between 16% (stage 4) and 38% (stage 1); T shortened between 14% (stage 4) and 25% (stage 1) and left ventricular systolic pressure decreased between 14% (stage 4) and 21% (stage 1) when prostaglandin E1 was administered during four stages of left ventricular pump failure, which ranged from a 20% decrease in [+dP/dt]max (congestive heart failure stage 1) to a 50% decrease in [+dP/dt]max (congestive heart failure stage 4). In contrast to normal animals, prostaglandin E1 caused an increase in left ventricular end-diastolic pressure during the more advanced stages of pump failure. Nevertheless the favourable cardiodynamic changes brought about by prostaglandin E1 administration might contribute, together with afterload reduction, to a general haemodynamic improvement during congestive heart failure. PMID- 2251297 TI - Identification and purification of a bovine corpora luteal membrane glycoprotein with [3H]prostaglandin F2-alpha binding properties. AB - A bovine corpora luteal membrane glycoprotein which coelutes from multiple chromatographic procedures with bound tritiated prostaglandin F2a ([3H]PGF2 alpha) has been identified and purified to homogeneity. The properties of this molecule include: an apparent molecular mass by polyacrylamide gel electrophoresis (PAGE) of 135 kD; glycosylation which resists endoglycosidases D and H but is susceptible to cleavage by the exoglycosidase sialidase; binding of the molecule to Wheat Germ Agglutinin Sepharose but not to Concanavalin A Sepharose or Soybean Agglutinin Sepharose; migration on O'Farrell 2-D PAGE (pI 3 10) to the acidic side of the gel; binding to DEAE-Cellulose at pH 7.5 which can be displaced with NaCl at concentrations above approximately 100 mM; and, when solubilized with Triton X-100, binding to Phenyl-Sepharose or Octyl-Sepharose columns. Lastly, a rabbit polyclonal antibody against this [3H]PGF2 alpha binding protein has been made which allows both Western blotting of the 135 kD protein as well as immunohistochemical staining of ovarian tissue in a manner expected from previous binding studies. Problems associated with membrane solubilization of the receptor and receptor renaturation are discussed. PMID- 2251298 TI - A monokine stimulates prostaglandin-E2 production by human amnion. AB - The studies reported in this communication were designed to test the hypothesis that products of mononuclear cells are capable of stimulating prostaglandin E2 production by human amnion. Conditioned media obtained from peripheral blood mononuclear cells were incubated with amnion cells in primary culture. A dose dependent increase in PGE2 biosynthesis was observed in response to increasing amounts of the conditioned media. These observations suggest that mononuclear cells produce a factor(s) capable of stimulating prostaglandin production by amnion cells. The signal responsible for the increased biosynthesis of prostaglandins by human amnion associated with parturition in the setting of intraamniotic infection may be of host origin. PMID- 2251299 TI - The necessity of placebo application in psychotropic drug trials. PMID- 2251300 TI - Mood curves of neurotic-depressive patients undergoing treatment with antidepressants: time-series analyses of experience with HTAKA model. AB - Statistical time-series analyses of single case data allow a sophisticated person centered evaluation of therapeutic effects. The possibilities and limitations of a new method of time series analysis are shown by the example of mood curves of neurotic depressive patients. The HTAKA model seems advantageous, because this procedure is less restrictive than other methods as regards the data basis. The cluster-analytical agglomeration of the single-case results indicates a sufficient response to antidepressants in about 40% of the patients who were treated with antidepressants in addition to psychotherapy. PMID- 2251301 TI - Study of the unidimensionality of the Bech-Rafaelsen Melancholia Scale using Rasch analysis in a French sample of major depressive disorders. AB - In a French sample of 73 major depressive disorders (according to the DSM III definition), the unidimensionality of the Bech-Rafaelsen Melancholia Scale was studied; firstly by means of traditional but not really valid methods (i.e., factor analysis and Cronbach's alpha), and second, using the Rasch logistic model. These methods would seem to show that the B.R.M.E.S. provides a unidimensional measurement of depression. PMID- 2251302 TI - Attachment and separateness. A dialectic model of the products and processes of development throughout the life cycle. AB - Various theories of psychological development can be characterized according to whether they are primarily separation or attachment theories and whether they emphasize primarily the processes or the products of development. A full understanding of psychological development requires an integration of theories of attachment and separation and of what is attained in the course of psychological development (the products), as well as the mechanisms (or processes) by which these products are attained. Discussion of a revised model of Erikson's eight stages of psychosocial development illustrates the importance of formulating a dialectical developmental model that describes the interaction between attachment and separation and between product and process. PMID- 2251303 TI - Play narratives in 36-month-old children. Early moral development and family relationships. AB - Whether there is significant moral development prior to the resolution of the oedipal conflict has been a source of debate between classic psychoanalytic and more recent clinical theories. We devised a play narrative technique, using standard story stems, to elicit 36-month-olds' representations of affective themes related to moral conflicts. Since morality is both influenced by interactions with significant others and involves dealing with the roles of others in the midst of conflict, we also explored narrative representations of the family. Results indicate that children as young as 36 months represent a considerable amount of moral development in narrative form. Children were able to articulate coherent stories about rules, reciprocity, empathy, and internalized prohibitions. Most remarkable was their ability to deal with alternative outcomes in order to resolve a moral dilemma. With respect to family relationships, the majority of the children represented a range of family figures who served as reparative agents and who initiated prosocial interventions for conflict. Interestingly, the children portrayed less difficulty with separation from parents when the parents were physically absent than when they were present but not available. We conclude that our narrative story stem technique offers promising opportunities for learning more about early moral development and family relationships in 3-year-olds. PMID- 2251304 TI - Enduring sadness. Early loss, vulnerability, and the shaping of character. AB - This paper describes the psychoanalysis of two individuals, a child (Andrew) and an adult (Quentin), who suffered from early disruptions in their families. Their fathers played prominent roles as caregivers during prolonged periods and buffered the traumatic loss of their mothers. Both Andrew and Quentin had family histories of depression and both developed depressive and characterological difficulties marked by disturbances in the regulation of aggression, with sadistic and masochistic features. Their early childhoods and experience of recurrent loss, longing, and anger were reconstructed during psychoanalysis. Psychoanalysis was therapeutically useful in relieving acute symptoms and in helping both patients move ahead in their development more securely and less burdened by diffuse, inner- and outer-directed rage. Andrew returned for psychotherapy twice, in early and late adolescence, and it was possible to follow the course of his character development during the transition from childhood into young adulthood. Using the clinical psychoanalysis as a base, the paper describes aspects of the development of character with a special emphasis on the roles of loss and the representation of aggression. PMID- 2251305 TI - The third individuation. The effect of biological parenthood on separation individuation processes in adulthood. AB - The subject of this paper is the Third Individuation, the continuous process of elaboration of the self and differentiation from objects which occurs in the developmental phases of early (20 to 40) and middle (40 to 60) adulthood. Although it is influenced by all important adult object ties, at its core are involvements with children, spouse, and parents, i.e., the family, the same psychological constellation that shaped the first (Mahler) and second (Blos) individuations. PMID- 2251306 TI - Boundaries, limitations, and the wish for fusion in the treatment of adolescents. AB - The centrality of boundaries to the adolescent experience is reviewed from a variety of perspectives, such as the development and consolidation of the self, superego internalization and authority, and the encounter between self and other. The study of boundaries through the experiential modes of Being and Doing leads to distinguishing two kinds of boundary experiences, one requiring separation and differentiation, the other leading to merger and fusion. Adolescence entails the integration of these two modalities so that identity formation and intimacy can take place. The implications for treatment are discussed and illustrated with a clinical vignette. PMID- 2251307 TI - The analysis of a latency boy. The developmental impact of separation, divorce, and remarriage. AB - John was a highly intelligent, unhappy boy who was failing to function academically and socially. This paper attempts to show how the cumulative stress between the parents resulting in divorce and remarriage affected a child with a predisposition to anxiety. The internal and external chaos wrought by disturbed and unpredictable parents distorted his development. His feelings of abandonment and bewilderment led to low self-esteem. The paper will illustrate how this influenced the analytic process and the areas in which treatment helped to restore him to the path of normal development. PMID- 2251308 TI - The role of fantasy in the treatment of a severely disturbed child. AB - This case study demonstrates the psychodynamic role of a system of fantasies that dominated the emotional life of a severely disturbed child. Transformations in these fantasies revealed her development of a more stable sense of reality and the capacity for object relations. PMID- 2251309 TI - The analyst's stance and the method of free association. AB - The concept of the analyst's stance is employed to organize a number of ideas about psychoanalytic work, past and present, especially from the viewpoint of the method of free association. Beginning with an emphasis on the intrinsic uncertainties and paradoxes of the analytic process, the author reviews the importance of words, the aim of mastering resistances (i.e., promoting freedom of association), and functional neutrality on the analyst's part. The problem of anonymity is considered from a number of angles. Two traditions of transference are described, deriving from Freud's overlapping early formulations. The distinction between old and new determinants in the two kinds of transference is useful and important in the analyst's stance. Attitudes toward insight, resistance, and conflict resolution are considered from the perspective of the distinction between divergent and convergent conflicts, with special emphasis on the role of punitive, unconscious self-criticism. PMID- 2251310 TI - An imaginary brother. His role in the formation of a girl's self image and ego ideal. AB - Motivated by narcissistic and libidinal strivings in a pathological family setting, the patient developed discordant identification systems which neither fused nor modulated each other. The structure of her wished-for self image with its autonomous tendencies was based on an Older Brother fantasy with which she identified. Her submissive self image was determined by an unconscious ideal modeled on her mother. These incompatible identifications continued in conflict. Enactment of the pattern determined by the maternal ideal led to object choices which evoked masochistic behavior, recognized by the patient as destructive to her ego aims. PMID- 2251312 TI - The velveteen rabbit. Fragment of an analysis. AB - This paper develops a psychoanalytic interpretation both of the popular children's story and of the process by which interpretation of the story unfolded within the writer's experience as an analysand. Questions of attachment and separation prove central to both investigations. PMID- 2251311 TI - Somatization and dream work. AB - This paper refers to somatization processes which correspond to organic disorders in the body or illness. In relation to it, the author discusses dream production and its development as major indicators to be used in following the course of treatment, as changes, both positive and negative, are reflected in the form, texture, and content of dreams. These points are illustrated by clinical material. PMID- 2251313 TI - Some theoretical and technical aspects of gender and social reality in clinical psychoanalysis. AB - Since the social order embodies and authorizes ideals of femininity and masculinity, a psychoanalysis of gender entails decisions as to how social reality figures in the clinical situation. This paper approaches social reality as part of a general problem of neurosis, in which all versions of normality are analyzed as aspects of resistance. What such an approach emphasizes about social ideals is their role in a psychopathology of conformity, which constitutes a stage in the development of neurosis. PMID- 2251314 TI - Adventure in the outdoors. Its importance in the development of an adolescent boy. AB - This exploration of how the analyst works uses a 15-year-old boy's description of an adventure in the outdoors as the starting point for a sequence of associations which led first to a passage from a Wordsworth poem and then to memories from the analyst's own childhood. The related themes of rite of passage and adolescent mourning are elaborated. PMID- 2251315 TI - Developmental aspects of self-esteem in the analysis of an 11-year-old boy. AB - This paper explores the vicissitudes of self-esteem in the analysis of an 11-year old boy. The paper highlights the complex interplay from different developmental periods that underlies the growth and sustaining of self-esteem. This interplay, catalyzed in the crucible of the transference, includes issues of evolution of affect states, self-structure, object relations, psychosexual development, conflict, and defenses. PMID- 2251316 TI - The oedipal organization of shame. The analysis of a phobia. AB - The affect of shame in its development and transformations plays an important role in the oedipal period, alongside guilt, as a source of unpleasure and a signal affect. Earlier experiences of shame, associated with loss of control, are now incorporated into the new meanings derived from oedipal conflicts. The analysis of a phobic woman shows how the shame of exposure, experienced by the patient in terms of body concerns, involved complex compromises representing impulses, defenses, and fantasies. Signals of shame anxiety helped to ward off guilty fantasies of love and hostility by motivating character traits in which even ordinary caring was renounced. In the analysis these traits were represented in a transference of defense. PMID- 2251317 TI - The development and functioning of the sense of shame. AB - An extensive literature on shame has not yet sufficiently addressed the nature and functioning of this affect from the psychoanalytic, developmental point of view. This paper tries to lay the ground for such a task. PMID- 2251318 TI - Orienting perspectives on shame and self-esteem. AB - The orienting perspectives for examining shame and self-esteem included phenomenological, developmental (from a linear and from a discontinuous point of view), pathogenesis, and modes of therapeutic action. The perspectives are overlapping but potential incompatibilities exist, especially in the area of therapeutic action. PMID- 2251319 TI - Comments on termination in child, adolescent, and adult analysis. AB - Termination phenomena in the psychoanalytic treatment of children and adolescents demonstrate the obstacles and resistances to a mutually agreed ending, the importance of reality considerations as part of the decision to terminate, and "restoration to the path of progressive development" as the overarching criterion for the start of a termination phase. The assumption of continuity among developmental phases allows us to apply what we learn from child analysis to termination of adult cases, and this new perspective reinforces the idea that child analysis is an untapped source of insights into the analytic process. PMID- 2251320 TI - The ego ideal. AB - An outline is given of the varied uses and meanings attributed to the term "ego ideal" in the current literature. The concept is clarified and defined, with special attention to its historical origins. The locus of the ego ideal is placed in the superego, and its structure and function are integrated with those of the superego. Criteria for differentiating superego precursors from superego proper are given, and the importance of the distinction is stressed. The clinical usefulness of these issues is illustrated by clinical examples. In addition, "narcissism" as it pertains to the ego ideal is explored, and there is a discussion of the distinctions between shame and guilt. PMID- 2251321 TI - Some issues affecting termination. The treatment of a high-risk adolescent. AB - This paper addresses some of the difficulties of termination in the psychoanalytic psychotherapy of a deprived, high-risk adolescent girl, who had two previous treatments. Some commonly referred to issues are explored: termination and the developmental process of adolescence; the relationship between termination, mourning, and internalization; the need for the resolution of the transference and careful monitoring of the countertransference; the importance of the transference resolution of the oedipus complex and related issues concerning preoedipal development and identification; and the consolidation of ego strength. PMID- 2251322 TI - Termination in midadolescence. AB - At the start of the terminal phase, the patient wrestled with the conflict of whether to leave treatment and establish himself as a self-reliant young man or cling to the analyst, who represented, ambivalently, significant protective power. The resolution of the transference neurosis during the termination phase of a six-year analysis in this midadolescent bore a strong resemblance to work with adults. PMID- 2251323 TI - The Secret Garden. A therapeutic metaphor. AB - This paper analyzes a work of children's literature, The Secret Garden by Frances Hodgson Burnett, to demonstrate a therapeutic process. Two children are able to resume normal development, and overcome pathological character traits, through the agency of new object relationships, peer group experiences, and favorable environmental influences. As a result, both attain the skills and ego functions of normal latency and prepuberty. Elements of this therapeutic process that resembles the psychoanalytic encounter and the therapeutic treatment milieu are highlighted and discussed. The central role of transference, with its similarities and differences in both settings, is emphasized. Finally, the metaphoric meanings of "secret gardens" are explored and connected with the enormous appeal of this book for its prepubertal girl readers. PMID- 2251324 TI - Alain-Fournier. Memory, youth, and longing. AB - The interweaving of life and art appears with unusual clarity in the work and personal history of this author of one novel. Examining them also affords insight into his neurotic burden and its relief through his writing. PMID- 2251325 TI - Who's afraid in Virginia Woolf? Clues to early sexual abuse in literature. AB - Virginia Woolf, by self-admission, was a victim of repeated sexual abuses. At age 5 or 6 she was sexually mishandled by her older half brother, Gerald Duckworth. In her teenage years another older half brother, George Duckworth, misused her repeatedly. As a result of these abuses, Woolf suffered the special signs and symptoms of long-standing childhood psychic trauma--sexual numbing, emotional distancing, self-hypnosis, splitting, and dissociation. She also suffered some of the more ordinary signs and symptoms common to most childhood traumas--fears, perceptual repetitions, and repetitions in behavior (in this case, in writing). Interestingly, Virginia Woolf's fictional characters manifest the very same signs and symptoms Woolf manifested all of her life. The occasional reader may treat Woolf's fiction, because of these "symptoms," in much the same way that an actual childhood sex abuse victim is often treated--with boredom, disbelief, and failure to respond. PMID- 2251326 TI - Reflections on the sense of entitlement. AB - This paper looks at entitlement as consisting of three possible modes: an appropriate adequate sense of entitlement; an excessive sense of entitlement; and a sense of entitlement which is not usually in awareness. The authors discuss some of the antecedents of an excessive sense of entitlement as well as certain specific family constellations and traumatic events which seem to encourage or facilitate its existence. Clinical examples are presented to show the importance of an excessive sense of entitlement--related to narcissism--as it appears in psychotherapy or psychoanalysis; yet it is also visible culturally and politically. Entitlement and narcissistic proclivities are viewed according to the developmental history as well as the clinical manifestations (intensity, frequency, duration, and spread). PMID- 2251327 TI - Portal aspects of memory overlay in psychoanalysis. An object relations contribution to screen memory phenomena. AB - Distortion in screen memories illustrates the unique manner in which part-object representations unite perceptions from different temporal periods. "Portal" aspects of a given source memory designate anachronistic distortions borrowed from perceptions at a subsequent time when the source memory and its full emotional significance attempted access to consciousness. The unconscious perception of recall at the subsequent occasion is represented by the appearance of portal details in the source dream. The portal concept is related to object relations theory and the psychology of memory. PMID- 2251329 TI - Acute morphine lowers brain stimulation reward thresholds in rats with depressed or elevated response rates. AB - The positively-reinforcing effect of acute morphine sulfate (MS) administration was assessed by concurrent rate-dependent and rate-independent measures of brain stimulation reward in male rats. An acute 4 mg/kg MS injection produced a rapid, statistically-significant decrease in reward threshold of 28.5%, when compared with saline control values, 45 min after injection. Response rates for brain stimulation delivery decreased by 60.6%, when compared with saline values during the period of maximum threshold change. Other animals, injected with an acute 1 mg/kg MS dose, exhibited significant threshold decreases (21.5%), relative to changes in saline values that occurred in a prior session, and response-rate increases of 23.1%, relative to saline-session changes, when the data were recorded 40 min after injection. The findings reported here demonstrate that the decreases in reward threshold produced by acute morphine administration are independent of the response-rate changes that occur and also support the idea that morphine's rewarding effect may be independent of the behavioral inhibition or activation that can result from the effects of different morphine doses. PMID- 2251328 TI - Antagonism of the anti-conflict effects of phenobarbital, but not diazepam, by the A-1 adenosine agonist l-PIA. AB - The present study examined the effects of the anxiolytics diazepam and phenobarbital, the A-1 adenosine agonist N6-R-phenylisopropyladenosine (l-PIA), and the A-2 adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) on conflict behavior. Water-restricted rats were trained to drink from a tube that was electrified (0.5 mA intensity) on a FI-29s schedule, electrification being signaled by a tone. After 3 weeks of daily 10-min sessions, the animals accepted a stable number of shocks (punished responding) and consumed a consistent volume of water (unpunished responding) per session. Different doses of l-PIA and NECA were then tested separately at weekly intervals. In addition, the effects of diazepam and phenobarbital were determined in animals pretreated with saline, l PIA, or NECA. Neither l-PIA (15-250 nmole/kg) nor NECA (2.5-20 nmole/kg) produced a significant anti-conflict effect when administered alone. Diazepam (1.25-10 mg/kg) or phenobarbital (10-40 mg/kg) administration to saline-pretreated rats resulted in a dose-dependent increase in punished responding (shocks received) with minimal effects on unpunished responding (water intake). Neither l-PIA nor NECA pretreatment reliably altered the effects of diazepam on conflict behavior. Pretreatment with l-PIA, but not NECA, significantly reduced the anti-conflict effects of phenobarbital on conflict behavior. These data suggest that phenobarbital, but not diazepam, anti-conflict responses may involve interactions with A-1 adenosine receptors. PMID- 2251331 TI - Effects of chlordiazepoxide and flumazenil on preference for punished and unpunished response alternatives in rats. AB - Male food-restricted hooded rats were trained to respond on a two-component multiple schedule. Reinforcement density was several times higher in one component than in the other. However, responses were intermittently punished with shock in the richer reinforcement component (conflict situation). Shock intensities were adjusted to produce mild and strong suppression of responding in two separate phases. Half of the rats controlled which component was operating (Preference group) and half did not (Yoked group). The effect of chlordiazepoxide (CDZ; 0, 1, 3, and 10 mg/kg; IP) was measured on component preference and response rate. Chlordiazepoxide increased both time spent in the conflict situation and response rate in that component. This is the first study employing a schedule that permitted these two behavioral indices to be measured independently in a conflict paradigm. Response rates were also increased in the unpunished response alternative, but to a lesser degree than in the conflict situation. The effects of CDZ were at least partially mediated by the benzodiazepine receptor because CDZ's effects were diminished by flumazenil (10 mg/kg; IP), a benzodiazepine antagonist. PMID- 2251330 TI - Environment-dependent effects of ethanol on DOPAC and HVA in various brain regions of ethanol-tolerant rats. AB - The development of tolerance to the behavioral and biochemical effects of ethanol was studied. Rats were made tolerant to ethanol by the administration of daily ethanol injections (3 g/kg, IP) for 7 and 28 days. Tolerance developed both to the behavioral (hypothermic, sedative) and biochemical (accumulation of dopamine metabolites in various brain areas) actions of ethanol. However, it was found that this tolerance to both the behavioral and biochemical effects of ethanol was no longer present when previously ethanol-tolerant animals were moved from their home environment and given a challenge dose of ethanol (2.5 g/kg; IP) in a new, unfamiliar environment. Our findings confirm that ethanol tolerance cannot be explained on the basis of a singular neurochemical event. The development of ethanol tolerance is due to a complex interaction between environmental, learning, and biochemical factors. PMID- 2251332 TI - Puff-by-puff sensory evaluation of a low to middle tar medium nicotine cigarette designed to maintain nicotine delivery to the smoker. AB - Puff-by-puff assessments of a range of sensory and subjective attributes were made for three cigarettes, with tar and nicotine yields of: 10.0 and 1.4; 17.0 and 1.7; and 8.8 and 0.8 mg/cigarette, respectively. Seven attributes were assessed: mouth impact, throat impact, chest effect, roughness, intensity of flavour, satisfaction and quality of flavour. Significant differences between the three cigarettes were obtained for most of these attributes. Principal component analysis of the data revealed three principal components related to the cigarettes under investigation. Components 1 and 2 accounted for approximately 47 and 28% of the total variance and component 3 only added a further 7%. Principal component 1 was a complex combination of intensity-related characteristics, i.e. mouth and throat impact, chest effect, intensity of flavour, roughness, while quality of flavour and satisfaction contributed to the separation of samples on principal component 2. However, the two major components could not be defined simply in terms of the yields of tar and nicotine for the products determined on a smoking machine. PMID- 2251333 TI - Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats: possible disruption of dopamine-dependent mechanisms of the nucleus accumbens. AB - These experiments compared isolation-reared and socially-reared rats in two complementary paradigms for measuring responding to signals of reward, both undrugged and following either systemic or intraaccumbens d-amphetamine (AMPH). In experiment 1, locomotor activity conditioned to food presentation was measured in rats exposed to a restricted feeding schedule. The interaction between this conditioned activity, AMPH administration (0.5, 2.0, 3.5, 5.0 mg/kg IP) and motivational state was measured. In experiment 2, hungry rats were trained to associate a compound light/noise stimulus with sucrose reward and were then implanted with guide cannulae in the nucleus accumbens. In the test phase, responding on one of two novel levers produced the compound stimulus (conditioned reinforcer; CR). Responses on the other lever had no effect. Each rat received four counterbalanced intra-accumbens infusions of AMPH (0, 3, 10, 20 micrograms). In both experiments, isolated rats responded more with stimuli associated with reward and this differential rearing effect was further exaggerated by AMPH. The isolation-induced sensitivity to these stimuli and to AMPH was critically dependent on motivational variables. Thus, in experiment 1 there were no differences between the groups when sated or during extinction and in experiment 2 the increased responding was restricted to the lever providing CR. Measurements of the locomotor response to intra-accumbens AMPH (0, 3, 10 micrograms) also revealed that isolated rats were more sensitive to a low dose of the drug when tested food-deprived in a relatively novel environment. These results suggest that the experience of isolation-rearing interacts either directly or indirectly with dopamine-dependent mechanisms of the nucleus accumbens to enhance the effects of reward-related stimuli. PMID- 2251334 TI - Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy. AB - In a study designed to examine the role of the genotype on sensitivity to drug induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development. PMID- 2251335 TI - Ethanol effects on delayed spatial matching as modeled by a negative exponential forgetting function. AB - Performance on delayed matching-to-position as a function of ethanol was investigated in rats and dose effects assessed by fitting an exponential decay model of forgetting to signal detection sensitivity scores. Three ethanol doses (0.25, 0.50, and 0.75 g/kg) and one isovolume saline control were examined. For further comparison, one dose of chlordiazepoxide (CDP; 5 mg/kg) and its saline control were also given. Forgetting functions were reasonably well described by the decay model under all treatment conditions. In addition, the functions's decay constant (-b) proved to be differentially sensitive to both drug and dose effects. Reduced decay estimates were obtained following the two lowest ethanol doses, the reduction being statistically significant for the 0.25 g/kg dose. In contrast, the function estimate of initial sensitivity, the intercept parameter (SI0), was not significantly affected by ethanol. Consistent with the low-dose ethanol effects, CDP significantly decreased the value of the decay parameter while leaving the intercept parameter unaffected. But unlike ethanol, the variance accounted for by the model for the individual data was less following CDP administration. Drug effects were interpreted using the exponential decay model of forgetting, and the results suggest independent discriminative control over SI0 and b. The significant effect of the low-dose sedative-hypnotics upon b, with no attendant effects upon SI0, is suggested to result from enhanced, spontaneous, delay interval mediation. PMID- 2251337 TI - Extinction and reacquisition of differential responding in rats trained to discriminate between chlordiazepoxide and saline. AB - In order to assess the resistance of drug discriminative responding to prolonged reinforcement omission, rats were trained to discriminate between either 6.0 mg/kg PO or 30.0 mg/kg PO. CDP and saline, using a food reinforced (V140-FR10) operant procedure. Dose generalization tests were conducted for both groups. Sessions were then run without reinforcement while drug (D) and saline (S) administrations were continued (extinction phase). After a maximum of 30 sessions without reinforcement, or when the rats emitted less than ten responses on either lever during three successive sessions (extinction criterion), reinforcement was reinstated. Finally, additional dose generalization tests with CDP were run. The discriminative responding controlled by the D and S administrations was not affected significantly by prolonged reinforcement omission in either group. For both groups, response rates were decreased and latencies to initiate responding were increased during the extinction phase. Response rate reduction occurred more rapidly for the drug condition in the high training dose group. This group also reached the extinction criterion sooner than the low training dose group. The reacquisition process occurred very rapidly. Response rates increased substantially after the first reinforcement had been obtained. After ten reacquisition sessions, response rates and latencies had reached values similar to those observed before extinction was initiated. Data revealed no differences between groups and the course of reacquisition did not differ between the S and D conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251336 TI - Antagonistic effect of physostigmine on ketamine-induced anesthesia. AB - Effects of physostigmine on ketamine-induced anesthesia and analgesia were studied in male Sprague-Dawley rats using behavioral tests. Rats were divided into six groups. Immediately after loss of the righting reflex following an intraperitoneal injection of ketamine 75 mg/kg, each group of rats was given an intraperitoneal injection of either physostigmine 0.05, 0.1, 0.2, 0.4, 0.6 mg/kg or saline as the control, respectively. Physostigmine 0.1 mg/kg caused the greatest antagonistic effect on ketamine anesthesia as indicated by sleeping time, duration of ataxia and motor coordination. The antagonistic effects of physostigmine were reduced by a dose of physostigmine of greater than 0.1 mg/kg. However, at no dose did physostigmine antagonize ketamine analgesia as indicated by the tail-flick latency. Physostigmine (0.4 and 0.6 mg/kg) itself had analgesic and motor-suppressive actions. It can therefore be presumed that there is a limited threshold of the dose of physostigmine which develops an antagonistic effect on ketamine anesthesia due to the motor-suppressive action. It is also confirmed that physostigmine itself produces analgesia, and does not antagonize ketamine-induced analgesia. PMID- 2251339 TI - Differential effects of apomorphine on prepulse inhibition of acoustic startle reflex in two rat strains. AB - Apomorphine disruption of prepulse inhibition (PPI) has been proposed as an animal model of sensorimotor gating deficits exhibited by schizophrenics. The effects of apomorphine on PPI of the acoustic startle reflex in male rats of Wistar and CD (Sprague-Dawley derived) strains were compared under identical test conditions. In Wistar rats, subcutaneous administration of 0.25-1.0 mg/kg apomorphine blocked PPI without affecting startle amplitude. In CD rats, apomorphine (0.3-3.0 mg/kg, SC) had no effect on PPI, but increased startle amplitude. Therefore, choice of rat strain is an important factor in the design of experiments studying apomorphine effects on PPI. PMID- 2251338 TI - Effect of chronic D-1 and/or D-2 dopamine antagonist treatment on SKF 38393 induced non-stereotyped grooming. AB - The effects of chronic D-1 and/or D-2 dopamine (DA) receptor blockade on a putative D-1 DA receptor-mediated behavioral function was studied in rats treated for 21 days with the selective D-1 antagonist SCH 23390, the predominantly D-2 antagonist haloperidol, or the combination of both drugs at the same daily doses. Four days after the last drug dose, the non-stereotyped grooming response to the selective D-1 agonist SKF 38393 increased in SCH 23390-pretreated rats decreased in haloperidol-pretreated rats compared to controls, but remained unchanged in animals receiving both drugs. Underlying DA receptor changes and the resulting imbalance between D-1 and D-2 receptor presumably contribute to these effects, suggesting that the upregulation of one DA receptor subtype may modify the expression of behaviors associated with the other subtype. PMID- 2251340 TI - Effects of scopolamine, trimipramine and diazepam on explicit memory and repetition priming in healthy volunteers. AB - The effects of scopolamine, an anticholinergic drug, of trimipramine, a tricyclic antidepressant with both anticholinergic and sedative properties, of diazepam and a placebo, on explicit memory and repetition priming were assessed using a free recall task and a word-stem completion task. Forty-eight healthy volunteers took part in this double-blind study. Diazepam provoked a dissociation between free recall, which was profoundly impaired, and word completion, which was spared. No significant changes in memory performances were observed in the scopolamine group; however, a significant correlation between explicit and implicit memory performances was observed in this group. At the low dose used, the effects of trimipramine on memory were mild. The results suggest that the cholinergic system is involved in the priming effect. PMID- 2251343 TI - [A comparison of the number of chromatid aberrations with dose, estimated from the frequency of dicentrics, in the cytogenetic study of lymphocytes in subjects involved in the accident at the Chernobyl Nuclear Power Station]. AB - A study was made of the frequency of chromatid aberrations in lymphocyte culture of subjects affected by the Chernobyl accident as a function of dose estimated by the incidence of dicentrics. The average number of chromatid aberrations was nearly the same within the dose range from 0 to 5 Gy exhibiting a tendency towards growth with dose. A high individual variability of the chromatid aberration frequency was observed. PMID- 2251341 TI - [D-Pen2, D-Pen5]enkephalin, the standard delta opioid agonist, induces morphine like behaviors in mice. AB - [D-Pen2, D-Pen5]enkephalin (DPDPE; 3-30 micrograms) and morphine (10 micrograms) both caused Straub tails, increased locomotion, and circling after ICV administration to ICR mice. DPDPE-induced tail stiffening was reduced when mice were pretreated with naloxone (0.5 mg/kg SC) or beta-funaltrexamine (10 micrograms ICV), but not with ICI 174864 (2 mg/kg SC), the selective antagonist at delta opioid receptors. These results point to (a) mu receptors mediating the tail stiffening and (b) the loss of delta receptor selectivity after 10 and 30 micrograms DPDPE. PMID- 2251342 TI - [Pressing problems of modern radiobiology in the light of the evaluation and prognosis of the aftermath of the accident at the Chernobyl Nuclear Power Station]. PMID- 2251344 TI - [Monitoring the seeds of chronically irradiated native populations of Plantago lanceolata L. The radiosensitivity of seeds]. AB - The method of provocative gamma-irradiation was used to study the radiosensitivity of seeds of three first post-accident reproductions of Plantago lanceolata L. within the thirty kilometer zone of Chernobyl. The radiation injury was severer among seeds taken in 1987-1988 from the areas with a higher level of radioactive contamination. PMID- 2251346 TI - [Systemic hemodynamics and cerebral blood supply following irradiation with highly lethal doses]. PMID- 2251345 TI - [The effect of cystamine and diethylstilbestrol on the proliferative activity and differentiation of bone marrow cells]. PMID- 2251347 TI - [The intracellular cycle of glucocorticoid receptors during gamma irradiation and the administration of dexamethasone, actinomycin D and cycloheximide]. PMID- 2251348 TI - [The role of serotonin and histamine in the neurohumoral mechanisms of postirradiation diarrhea in rats]. AB - In experiments with rats exposed to 200 Gy radiation it was shown that the diarrhea effect of serotonin under the effect of radiation is implemented via D- and M-type receptors, and that of histamine via H1 and H2 receptors. Serotonin and histamine, that were released under the effect of radiation from endocrine and mast cells of the digestive tract, stimulated the propulsion activity of the intestine whereas histamine, in addition, inhibited the absorption process. It is suggested that serotonin and histamine antagonists should be used as means of preventing of radiation-induced diarrhea. PMID- 2251349 TI - [The effect of highly intensive irradiation on the functional status of the brain in monkeys]. AB - In experiments with Macaca fascicularis a study was made of early manifestations of the central nervous system (CNS) disturbances caused by exposure to 24 MeV electrons (45 Gy). The results obtained permit us to distinguish two main ways (stereotypes) by which a clinical picture of early postirradiation period develops: "comatose" and "non-comatose". A general clinical characteristic of each stereotype and stages of their development are presented. The postirradiation disturbances of nervous and psychic activity of monkeys are considered within the framework of the concept concerning acute reactions of exogenous type. It is suggested that the course of the early postirradiation period is conditioned by the "involvement" of some phylogenetically determined, universal systemic mechanisms of the CNS response to external harmful effects. PMID- 2251350 TI - [The activity of carbohydrate metabolic enzymes in bone marrow cells of rats with radiation injuries]. AB - The influence of ionizing radiation (154.8 mC/kg) on activity of some carbohydrate metabolism dehydrogenases in cells of the whole and fractionated rat bone marrow has been investigated. Different glucose metabolism units differently responded to radiation, the highest radiation response being exhibited by pentosophosphate cycle processes. The pattern of changes in the enzyme activity of different myelokaryocyte populations was shown to depend directly on the functional specialization of cells and the energy exchange types predominated in them. PMID- 2251351 TI - [The impairment of antitoxic antitetanus immunity due to the combined effect of radiation and heat]. AB - In experiments with mice a delay was noted in the development of secondary immune response to revaccination with a tetanic anatoxin after the combined effect of radiation and heat; the maximum antibody formation occurred at later times. The low level of antitoxins within the first 10 days after the combined effect of radiation and heat correlated with the low tetanus resistance of animals. PMID- 2251352 TI - [Mathematical modeling of the dynamics of erythropoiesis and granulocytopoiesis in mammals exposed to acute irradiation]. PMID- 2251353 TI - [Characteristics of the development of radiation sickness in guinea pigs exposed to non-uniform irradiation in highly lethal doses]. AB - Certain peculiarities have been revealed in the development of radiation sickness in guinea pigs subjected to nonuniform irradiation with superlethal doses. With electron and gamma-neutron radiation LD50/1.5 was 116.11 and 114.48 Gy respectively, when delivered to whole body, and 133.40 and 111.72 Gy when delivered to the posterior part of the body. PMID- 2251354 TI - [The effect of analgesics on hemodynamic indices following irradiation with high doses]. AB - With radiation doses of 10 and 150 Gy morphine does not change the arterial tension and the pressor nociceptive reactions of rats. Clopheline delivered in an analgesic dose invokes a pressor reaction of the haemodynamics after irradiation with a dose of 10 Gy, but it is ineffective after superlethal doses. PMID- 2251355 TI - [The applicability of the concept of morpho-physiologic metabolic factors to the modification of the distribution of 239Pu deposited in the respiratory organs]. AB - At the stage of intensive resorption of plutonium from lungs to blood the competitive per os administration of an iron preparation increased plutonium excretion from blood. As a result, soft tissues were enriched with plutonium at an early stage of metabolism. However, at the end of the experiment (30 days) the radionuclide content of soft tissues dropped to control values. Simultaneously, the share of plutonium deposited in bone tissue decreased considerably and that of the radionuclide eliminated from the body increased throughout the entire period of observation. PMID- 2251356 TI - [The effect of laser puncture on the functional indices of the mammalian body]. AB - Biologically active points (acupuncture points) and reflexogenic zones of Wistar rats of different age were exposed to He-Ne laser radiation with the subsequent control of acetylcholine esterase activity, electric parameters of skeletal muscles and heart, and physical activity. Laser puncture was shown to increase the sympathetic nervous system tonus which was manifested by the decreased acetylcholine esterase activity and increased heart rate. Laser puncture stimulated the growth of membrane potential and increased considerably the performance capability of animals, particularly of three-month-olds. PMID- 2251357 TI - [The effect of microwave irradiation on the peroxide modification of low density lipoproteins in human blood serum]. AB - In experiments in vitro the electromagnetic field of 2375 mHz, 500 microW/cm2 was shown to influence peroxide modification of low density lipoproteids. It was also shown that this modifying effect was prevented by high density lipoproteids that decreased the level of lipid peroxidation. PMID- 2251358 TI - [The effect of microwave irradiation on the status of the thyroid gland]. AB - Multiple irradiation of rats with microwaves of continuous generation (2450 MHz, 1 mW/cm2) increased and of pulsed generation (3000 MHz, 0.1 to 2.5 mW/cm2) decreased the functional activity of the thyroid gland with no changes in the triiodothyronine and thyroxin in blood serum. The role of the thyroid gland in inducing behaviour effects of microwaves was demonstrated by the method of extirpation. PMID- 2251359 TI - [Postradiation changes in the functioning of the systems of lipid peroxidation and phospholipase hydrolysis in the cellular formations of the brain]. AB - A study was made of the effect of irradiation with lethal and superlethal doses on lipid peroxidation and endogenous phospholipase hydrolysis in the enriched fractions of neurons and glia. Severe and irreversible changes occurred in a lipid membrane component of both neuronal and glial fractions of the brain under the effect of ionizing radiation. PMID- 2251360 TI - [Interphase death of dividing cells. Relation of the death of cultured Chinese hamster fibroblasts to the inter- and extracellular pH]. AB - In studying interphase death (ID) of dividing cells from Chinese hamster fibroblast culture a differently directed relationship between ID rate and pH has been shown: the ID rate increases with pH increasing from 6.6 to 8.1 and decreases with pH from 5.0 to 6.6. The dependence is the same as that observed with lymphoid cells. With radiation doses increasing from 100 to 600 Gy and pH defined, the ID rate increases. PMID- 2251362 TI - [Cataractogenic action of accelerated carbon ions with energies of 300 MeV/nucleon]. AB - The influence of carbon ions of 300 MeV/nucleon on the incidence of lenticular opacity has been studied on mice. The cataractogenic efficiency of low carbon ion doses (0.003 to 0.5 Gy) is higher than that of gamma-radiation. The threshold dose of carbon ions is 0.05 Gy. The RBE ratios vary from 30.4 to 11.1 as the period of the postirradiation observation increases from 20 to 50 weeks. PMID- 2251361 TI - [The effect of irradiation in lethal and highly lethal doses on arterial pressure and hemodynamic nociceptive reactions]. AB - It has been found that the effect of whole-body gamma-irradiation with doses of 10 and 150 Gy on the haemodynamics regulation varies. Thus, the dose of 10 Gy does not change the arterial tension and the dose of 150 Gy decreases the arterial tension 6 and 24 hr after irradiation, the nociceptive reactions of haemodynamics being invariable with both doses. PMID- 2251363 TI - [The effect of a U-2 fraction of a tortoise spleen extract on the formation of an ectopic locus of hematopoiesis]. AB - The implantation of a bone marrow fragment of intact mouse donors below the kidney capsule of irradiated (7 Gy) recipients leads to the formation of the haemopoiesis locus that somewhat exceeds, by mass and cellularity, the new-formed locus of control animals. The U-2 fraction of a tortoise spleen extract administered to recipients irradiated with the same dose increases the mass and cellularity of the haemopoiesis locus by 2.2 and 4.9 times respectively. PMID- 2251364 TI - [The functional status of the small intestine in rats in the dynamics of a bone marrow form of acute radiation sickness]. AB - A study was made of 75Se-methionine absorption rate and contraction and choline reactivity of smooth muscle cells of rat jejunum longitudinal layer. Whole-body X irradiation with a dose of 5.8 Gy (LD50/30) caused a sharp decrease in the rate of absorption of 75Se-methionine by the blood from the intestine on days 3--4 after irradiation followed by an incomplete recovery of absorption by the 14th day. At the height of acute radiation sickness there was an 8- to 10-fold decrease in the sensitivity of the smooth muscle cell membrane to acetylcholine the contractile capacity being retained. This was perhaps the cause of the intestine motor activity inhibition. It is concluded that rat intestine functions are suppressed considerably with the bone marrow form of acute radiation sickness. PMID- 2251365 TI - [The protection of mice against x-radiation using sodium succinate]. AB - Dynamics of mouse resistance to X-radiation was studied after single and double injection of sodium succinate in doses of 2.5 and 10 mmol/kg. The criteria by which the radioprotective effect of the agent was estimated were: survival rate, spleen mass, and DNA content in the bone marrow. PMID- 2251366 TI - [Long-term results of local x-irradiation of rats]. PMID- 2251367 TI - [The cytotoxic activity of natural killer cells exposed to the joint and separate actions on the body of 239Pu, hexachlorobutadiene and tributyl phosphate]. AB - Wistar rats were subjected to a single exposure to 239Pu nitrate through inhalation with the subsequent procedure of imitation of inhalation or without it (the amount of 239Pu deposited in the lungs in 24 hr was 8.9 +/- 1.9 kBq/lung) and inhalation of hexachlorobutadiene and tributyl phosphate within one month in a combination with the radionuclide or without it. There was a 1.5-fold increase, above additive, in the harmful effect of 239Pu and chemical agents on the function of natural killers as observed 15--30 days after the combined exposure as compared to individual inhalation. On days 120 to 240 cell cytotoxic activity in rats of all groups was normalized to reach or to exceed the intact control. PMID- 2251368 TI - [The effect of the combined inhalation of tributyl phosphate, hexachlorobutadiene and 239Pu on the blood system in rats]. PMID- 2251369 TI - [Determination of the content of 137Cs in the human body]. PMID- 2251371 TI - [Scabies--1988]. PMID- 2251370 TI - [Diarrhea in infants under 2 years of age--1988]. PMID- 2251372 TI - [Rabies among humans and animals--1988]. PMID- 2251373 TI - [Brucellosis--1988]. PMID- 2251374 TI - [Trichinosis--1988]. PMID- 2251375 TI - [Taeniasis--1988]. PMID- 2251376 TI - [AIDS and HIV infections--1988]. PMID- 2251377 TI - [Infectious diseases in Poland compared with the epidemiological situation in Europe and in the world]. PMID- 2251378 TI - [Measles--1988]. PMID- 2251379 TI - [Whooping cough--1988]. PMID- 2251380 TI - [Scarlet fever--1988]. PMID- 2251381 TI - [Epidemic parotitis (EP)--1988]. PMID- 2251383 TI - [Rubella--1988]. PMID- 2251382 TI - [Influenza--1988]. PMID- 2251384 TI - [Cerebrospinal meningitis and encephalitis--1988]. PMID- 2251385 TI - [Bacillary dysentery--1988]. PMID- 2251386 TI - [Food poisoning--1988]. PMID- 2251387 TI - [Botulism--1988]. PMID- 2251388 TI - [Viral hepatitis--1988. Total number of cases]. PMID- 2251389 TI - [Tetanus--1988]. PMID- 2251390 TI - [Some parallels between results of infant observation and clinical observations of adults, especially borderline patients and patients with narcissistic personality disorder]. PMID- 2251391 TI - [When it is not the patient who pays]. PMID- 2251392 TI - ["Archaic matrix of the oedipus complex"]. AB - The clinical implication of Janine Chasseguet-Smirgel's concept of the "archaic matrix of the Oedipus complex" is examined, the resulting deeper understanding of the Oedipus myth is considered. A discussion follows of Chasseguet-Smirgel's way of using this concept in her historical evaluation of German Romantism with regard to the Nazi times and nowadays politics of the Westgerman Green Party. PMID- 2251393 TI - [A controversial use of psychoanalysis and the question of neutrality. Open letter to Johannes Cremerius]. PMID- 2251394 TI - [Fast electron beams in radiotherapy. Physico-dosimetric basis]. AB - The author starting from the electron beams production describes their interaction with matter in terms of stopping and diffusion. The "dose" and its spatial distribution is considered the physical parameter more suitable to describe the electron beams characteristics. Particularly, it is outlined that the experimental depth penetration curve of dose in water, can provide the parameter evaluation useful to characterize the electron beams both qualitatively and quantitatively, i.e.: beam dimensions at the entrance surface; mean energy Eo; maximum dose (Dmax) depth, R100; surface dose, Ds (% Dmax); depth of 50% of Dmax, R50; practical range, Rp; therapeutic range, R85. The operative steps are described as referred to the National Protocol of Standardization (basic dosimetry). PMID- 2251395 TI - [Preliminary evaluation of the clinical use of a system for intraoperative radiotherapy with electrons (IORT)]. AB - The preliminary evaluation of the dosimetric characteristics of a dedicated intraoperative electron beam therapy system is described (Bionix Corporation). The linear accelerator is the Varian 2100 C with electron beam energies of 6, 9, 12, 16 e 20 MeV. The isodose distribution for each of 15 available applicators (5 plane and 10 beveled) has been studied with a water phantom. The problems of the homogeneity of dose distribution, scattered and leakage radiation outside the applicators and X-ray contamination of the electron beams have been addressed, at the nominal 20 MeV energy for exemplification. The accurate knowledge of such physical and dosimetric properties are necessary for the implementation of the IORT techniques in terms of choice of the applicator size and electron beam energy for tumor coverage and dose sparing of critical organs. PMID- 2251396 TI - [Intraoperative radiotherapy with electrons: construction of facilities and dosimetry]. AB - The technical complexity of intraoperative radiotherapy (IORT) requires modification of the standard physical and dosimetric methods used in external electron beam therapy. At the Radiotherapy Department of Ospedale S. Chiara in Trento a number of technical innovations have been developed, including an electron beam applicators system and related devices. Ionometric and film dosimetry have been used to obtain relative dose distributions of clinical electron beams in phantoms. PMID- 2251397 TI - Electron beam therapy of primary tumors of the skin. AB - High energy electrons have, in comparison with 50-100 kV X rays, definitive advantages in treating large, thick or deeply infiltrating skin cancers. Moreover, a skillful therapeutic policy (fractionation, use of acrylic absorbers, shrinking field technique) often leads to excellent late results, with none or only insignificant side effects especially on bone and cartilage. PMID- 2251398 TI - [Role of accelerated electrons in the therapy of advanced-stage skin epithelioma advanced stage: analysis of 31 cases]. AB - Electron beam therapy is the superior modality of treatment for advanced skin cancer or in specific anatomical situations. The authors report the results for the electron beam therapy of 31 patients with advanced skin carcinoma. There were 15 squamous cell carcinomas, 11 basal cell carcinomas and 5 mixed, basosquamous cell carcinomas. All lesions were 3 cm or greater in maximum diameter. With follow-up ranging from 1 to 6 years, 28 patients have not evidence of disease, 1 is dead with disease, 1 is alive with suspicious residual disease and 1 is alive with recurrence. Acute and late complications are acceptable; bone, cartilage and soft tissue necrosis are not reported. The treatment results are similar to those in the literature and show the advantages of the electron beam irradiation for advanced skin carcinomas. PMID- 2251399 TI - [Use of fast electrons in oncologic therapy. More than a decade's experience]. AB - Criteria of choice in the utilization of fast electrons in radiotherapy on the basis of 2400 cases and 13 years of experience in the radiotherapy department of Cancer Institute in Milan are discussed. In the opinion of the authors fast electrons represent the most rational treatment to homogenize or differentiate the dose distribution according to space as a complementary technique after first time treatments by different ionizing radiation. Authors demonstrate also that fast electron treatment is the most rational technique for metastases in the retina and for recurrence of rhinopharynx cancer. Radiotherapy by fast electrons allows to deliver to the patient's body on integral dose lesser than with ionizing radiation of other type. Sequelae are regarding in most of the cases soft tissues and are caused by an unrecognized distribution of dose delivered by the ionizing radiations of other type in the first time treatment more than by difficulty im dosimetry of post-electrons. PMID- 2251400 TI - [The use of high energy electrons in the field of oncology. Experience of the O. Alberti Radio Institute of Brescia]. AB - The vast clinical experience of the "Istituto del Radio" (Brescia) in electron beam therapy (2-18 MeV Betatron, 1964-1974; 5-21 MeV Microtron accelerator, 1974 onwards) leads to underline three possible risks: the underestimation of the lesion thickness, the underestimation of the field dimensions, the exclusive use of electrons to give the whole tumour dose. Both in ENT tumours and in breast cancer electrons must be associated with high energy photons, in order to improving the clinical results with reduced risks of severe late effects. The exclusive use of fast electrons in cancer therapy is only indicated in "particular and rare" cases. PMID- 2251401 TI - [A decade's experience with electron radiotherapy]. AB - The experience related to 1170 patients treated with electron beam between 1979 1988 at Radiation Therapy Department in Pisa is reported. Beam dosimetry and dose distribution in tissue, patients contour and other parameters have been analysed as main important factors to optimise this technique. Electron beam therapy offers important contributions to the management of peculiar types of cancer because of the radiotherapy treatments optimisation and the reduced normal tissue reactions. PMID- 2251402 TI - [Clinical radiobiology of fast electrons]. AB - The characteristics of microdosimetry, in terms of "lineal energy" value distribution, differ widely between high energy photons and electrons, so as to explain the existence of measurable RBE differences. Nevertheless one can accept for clinical purposes the RBE value 0.9 and a correlated dose increment of 10%. Most important are the macrodosimetric features of electron beams. As far as the skin reactions are concerned, they depend on many factors and are gaining a new relevance in clinical radiotherapy, being a guide in the treatment policy for a given patient. PMID- 2251404 TI - [Electron beam radiotherapy for loco-regional recurrence of breast cancer]. AB - 125 cases of recurrent breast carcinoma (skin nodules or regional lymphnodes) after the primary radical treatment have been treated from 1975 to 1980. Most of these patients were irradiated with 6 MeV electron beams at 50-65 Gy; some of them with 20 MeV electrons. A complete response followed in 68% of lesions, a partial response in 23.2%. The survival at 5 and 10 years was respectively 25.6% and 8.8%. Low energy electron beam therapy is therefore an efficient way of treating loco-regional recurrences of breast carcinoma, after the failure of a radical primary treatment. PMID- 2251403 TI - [The use of electrons in oncologic radiotherapy: our experience]. AB - The authors describe the interaction of electrons with tissues, the characteristics of depth isodose curves with sharp dose fall-off. These characteristics reduce the utilization of electron therapy only for tumors situated some 5 cm depth below the skin surface and with regular surface. The authors report their experience from 1978 in the treatment of vulvar carcinoma, chest-wall recurrences from breast carcinoma, and cutaneous lymphomas. All these neoplastic diseases were treated with electron beam of adequate energy. Initially betatron was used, successively a linear accelerator (Siemens) about for two years. Results obtained in the treatment of vulvar carcinoma are reported. Two and five years disease free survival rates was respectively 33% and 19% (it is remarked the importance of prophylactic treatment on inguinal lymphnodes). Local control observed in 44 patients with cutaneous lymphomas was 85% until three years; a greater number of recurrences was observed in centrocytic-centroblastic lymphomas. Moreover, local control of breast recurrences was 65% with 5 years survival rate of 22% (34% in patients with only one skin recurrence). Only 22% of the further local failures appear within the treatment field while 78% appear out of field. PMID- 2251405 TI - [Total skin irradiation with electrons for mycosis fungoides: criteria for the choice of technique and experimental dosimetry]. AB - The initial lesions of mycosis fungoides are confined to the skin at a depth of about 1 cm. Wide fields irradiation with low energy electron beams is therefore the treatment of choice for the first stages of the disease. The authors have analysed the various treatment techniques of total skin electron beam irradiation reported in the literature. Dosimetric and practical features are considered. The angled beams technique seems to fit better the needs of a common Radiation Therapy Department. A treatment system with six pairs of 3 MeV electron beams is described and preliminary dosimetric measurements of a similar system that employs 6 MeV electrons are reported. PMID- 2251406 TI - [Physico-technical aspects of total skin irradiation with high-intensity-dose electrons]. AB - The authors have addressed the physical and technical problems involved in the total skin irradiation with a linear accelerator Varian Clinac 2100 C expressly preset for this modality with electrons of 6 MeV nominal energy and dose rate of about 2500 UM/min at the isocenter. The six dual field technique has been implemented and the effect of interposed degrading filters has been evaluated with film dosimetry on an anthropomorphic phantom. It was verified that the total skin electron irradiation expressly offered by the manufacturer as an established treatment option on the Clinac 2100 C with high performance ionizing chambers and high dose rate makes the all procedure safer and simpler. PMID- 2251407 TI - Use of electrons for radiation therapy in France. AB - The development of high energy radiotherapy equipments in France between 1950 and 1990 is analyzed. The use of betatrons after a growth between 1960-1970 decreased progressively from 1975 in favour of linear accelerators (133 in 1989). Cobalt therapy, rapidly grown up between 1960 and 1980, has reached a plateau phase with a trend to being progressively substituted by low energy linac. The dosimetric aspects are considered: calibration of electron beams, quality control and treatment planning. About 22000 cancer patients were treated in 16 Centres in 1983; of these only 23% (mean value) received electron therapy, but the number varies greatly from one center to another (9-45%). The major indications for electrons in France are: neck nodes, operated breast, internal mammary chain. The general trend is to restrict their use to lesions not deeper than 4-5 cm and first of all to employ them as a boosting treatment, after an X ray irradiation. PMID- 2251408 TI - [Total skin therapy with electron beams. I. Physical and geometric factors]. AB - The study pf physical and geometrical factors influencing dose distribution is necessary in performing the Total Skin Electron Therapy. The authors examined some aspects. Photographic emulsions in humanoid phantom were used for dosimetry. The techniques uses 6 dual fields at 320 cm treatment distance, with a degrading lucite filter 100 x 200 x 0.6 cm3 at 20 cm from the patient. Absorbed dose and energy were determined according TG 30 and 21 AAPM. The position of degrading filter was recognized to be the main factor influencing dose rate, penetration depth and dose homogeneity. PMID- 2251409 TI - [Total skin therapy with electron beams. II. Clinical results in mycosis fungoides]. AB - Between 1985 and 1989, 19 patients with mycosis fungoides were treated by Total Skin Electron Therapy (TSET). Overall and disease-free survival at 3 years were 72% and 40%. The complete remission (CR) rate was 100% in patients with plaque and 33.3% in those with tumor masses; patients with negative nodes had a 90% CR rate whereas in those with adenopathy the rate was 55%. Overall and disease free survivals were also correlated with these factors. PMID- 2251410 TI - Electron backscattering. Implication to electron dosimetry. AB - Plane-parallel electron chambers have structures made of plastic materials of low atomic number which do not provide the same scattering into the sensitive volume as water and suitable correction factors are therefore required to allow for this effect. Hunt et al. (1988) measured electron backscatter in low atomic number materials and this data was, in this work, analyzed together with the experimental data obtained for higher atomic number materials published earlier (Klevenhagen et al., 1982). It was found that both sets of data correlate well and fit to an empirical exponential expression for which the necessary calculation parameters were derived. This expression enables suitable backscatter correction factors to be calculated for materials of atomic numbers between 4 and 82, including plastics, and electron energies between 3 and 35 MeV. The deficiency of backscatter was evaluated for the most popular materials used in the construction of electron chambers and this data may be used for corrections. PMID- 2251411 TI - The radiotherapeutical use of high energy electrons in West Germany. AB - Germany has always deserved a great interest to electron beam radiotherapy (betatron, linear accelerator). At St. Vincentius Hospital in Karlsruhe the percentage of electron treated patients grew up in the years from 15% to 45%. Electron energies between 7 and 12 MeV are the most commonly used. Major RT Centres need a wider range of energies (5/7-20 MeV), but the minor ones should have at least electron beams of 5-12/15 MeV. PMID- 2251412 TI - [Distribution of linear accelerators in Great Britain. Use of fast electrons and their main applications]. AB - The features of the electron beam that make it a unique therapeutic tool, are related to physical characteristic rather than to any special biological effectiveness. The advantages of the dose distribution pattern are greatest at low energies (under 20 MeV), suggesting the use of electrons for irradiation of superficial tumors with the sparing of underlying tissues. Modern clinical electron practice demands electron treatment beams offering a high degree of purity, uniformity and the steepest possible fall-off of dose beyond the treatment volume. There are approximately 135 Linacs installed in UK, and approximately half of them have electron capacity with range of energy between 4 and 15/20 MeV. Compared to photon beams, 10% of treatment load is for electrons with a maximum of 15% in very specialised centres. PMID- 2251413 TI - Current use of electron beam therapy in the United States. AB - Owing to their physical characteristics, electron beams are a crucial component in radiotherapy of human tumors. Besides their main indications (skin cancers, head and neck tumors, breast, chest wall recurrence, low pelvic tumors) other types and sites of malignancies are to be considered: skin lymphomas, soft tissue sarcomas, Kaposi's sarcoma in AIDS patients, as well as Intra Operative Radiotherapy. PMID- 2251414 TI - [Radiotherapy with electron beams in Italy]. AB - The use in Italy of high energy electrons in radiotherapy is analyzed following the answers of 29 Centres to a questionnaire. The CISDR (AIFB) dosimetric protocol, some noticeable clinical, technical and dosimetric experiences are underlined. At the moment computerized dosimetry, intraoperative radiotherapy and total skin electron irradiation are the topical subjects in high energy electron radiotherapy. PMID- 2251415 TI - [Accuracy of distribution of the doses obtained with electron beams of irregular shape and in the presence of inhomogeneous structures]. AB - The authors have addressed the problem of dose distribution calculation accuracy when irregularly shaped electron beams are used and structural dishomogeneities are present. The mathematical model used for the electrons from the "scattering foil" and from the colimator walls is the "gaussian pencil beam", and the total dose is obtained by adding to the above mentioned components the dose from the electrons diffused by the field defining frame and from bremsstrahlung photons. Depth dose curves, with and without frames, are compared with a satisfactory correspondence between the calculated and the measured curves. The calculation method is considered accurate within 2% of dose and 2 mm in position. When dishomogeneous structures are present and treated as semi-infinite layers, corrections are referred in 2-D to a single anatomical section and can be extended to 3-D if a sufficient number of sections is available for the whole volume definition. However current algorithms need to be improved when there is the possibility to use a much more powerful hardware. PMID- 2251416 TI - [Dosimetry problems of radiotherapy with electron fields of small dimension or partially shielded]. AB - In radiotherapy in many clinical cases it is necessary to employ electron beams of small dimensions and/or shielded in order to have shaped fields. It is well known that percentage depth dose and output depend on the energy, on the field dimensions and on the collimation system. In order to evaluate separately the influence of these factors measurements were performed with electron beams of nominal energy from 6 to 14 MeV, of a linear accelerator Philips SL/75. Measurements were performed in standard dimension phantoms and in a small perspex phantom, 3 cm diameter. The values obtained in this small phantom were compared with the ones obtained for the same diameter collimator in order to have information on effect of missing lateral scatter equilibrium. Other measurements for an applicator, open and partially shielded, were performed. The results of these measurements are shown in graphics. Data show that the percentage depth dose ionization curves at fixed energy depend on the collimator linear dimension in particular, when these dimensions are smaller than the range of secondary electrons. However it is evident the difficulty to find a correlation between linear field dimensions and the percentage depth ionization curves. In the clinical practice it is important to take into account this difficulty when employing small or irregular electron fields. PMID- 2251417 TI - [Inhomogeneity of electron beam dose distribution]. AB - The radiation therapy employing high energy electron beams took place in superficial or near-superficial target volume treatments. The author describes the dose distribution in the patient whose body is not homogeneous for the presence of bone structures or air cavities that may involve localised perturbations of the dose distributions. Several methods have been developed to obtain the correct dose distribution including the influence of depth, field size and energy. The author describes how the dose distribution changes when the body contour at the beam entrance is bent and oblique. Artificial inhomogeneity like compensators, bolus and adjacent electron beam field may give unexpected small overdose areas. PMID- 2251418 TI - [Personalized low-melting alloy shield for high-energy electrons in the treatment of superficial neoplasms of critical or esthetically important regions]. AB - Individualized Cerrobend beam shapings for high-energy electrons have been utilized in the treatment of superficial tumours located in aesthetic or critical regions. Individualized cellulose acetate masks have been used as immobilization device. Measured transmissions through Cerrobend ranged from 0.5% at 4 MeV to 8.5% at 18 MeV. Phantom dosimetry showed a poor influence of Cerrobend on PDD (percentage depth doses). Output factor variations appeared to depend on electron energy and shielded area. It is very important to perform either empirical measurements or to adopt semiempirical models in order to exactly calculate those output factors. Three clinical examples are presented: the utilization of immobilization device and field shaping are illustrated with the main aim of sparing the dose to critical organs. PMID- 2251419 TI - [The recombination factor in an ionizing chamber used for dosimetry of a linear accelerator]. AB - The authors starting from the discussion of Boag address experimentally the ion recombination in an ionizing camera. They outline the fact that several basic dosimetry protocols do not highlight the importance of the used radiation sources, beam width, ionizing camera dimensions, even though they mention to take into account the recombination factor. The authors determine experimentally the recombination factor with two kinds of ionizing camera, one cylindrical and the other flat, on a linac pulsed and scanned radiation beams. As a result it ensued that it is advisable to use a Markus type ionizing camera rather than a cylindrical one, especially when scanning beams are used, to reduce the recombination phenomena. PMID- 2251420 TI - [Dosimetry of electron beams: verification of the accuracy of an automatic dosimeter and a system for treatment planning]. AB - This study is part of a quality assurance programme evaluating the performances of two connected on-line systems (automatic dosimeter and treatment planning) and verifying the correctness of the applied algorithms and the accuracy of the basic beam data. We compared PDD measured in an automatic water phantom using a p-Si detector with point doses using an ion-chamber, for electron beams from a linac. To record dose distributions of scanned electron beams, the detector measurement time was triggered by the frame scan frequency. Data were automatically transferred to the treatment planning system by an interface. Measured and calculated isodose charts were compared for perpendicular incidence fields. Relative dose values calculated, in axis and off-axis points, were compared with those determined by the ion-chamber in the following situations: perpendicular and oblique incidence, different SSD. PMID- 2251421 TI - [Verification of 3 computerized systems for drafting a plan for treatment with electrons]. AB - The electron beam treatment planning systems, with the availability of more and more developed hardware for complex calculation algorithms, need quality controls of accuracy and comparability of treatment plans from different systems. In this paper three systems have been evaluated; their similar computation algorithms (pencil beam) have been used but in some conditions (beam reconstruction, oblique incidence and dishomogeneity) different results have been drawn. The basic data (PDD, dose profile, etc.) were the same for every system, therefore it has been observed that different results are mainly due to differences in: a) input of parameter values, b) calculation algorithm approximations, c) image acquisitions and elaboration. PMID- 2251422 TI - [Simulation of an instrumental head for 6 MeV electron beam therapy]. AB - Simulation of a therapy head for 6 MeV electron beams. We present the results of a simulation, performed using a Monte Carlo method, of depth dose curves in water for electron beams of initial kinetic energy of 6.4 MeV, generated by a radiotherapy microtron MM22 Scanditronix. The Fortran code in EGS4: comparison is made between simulated curves, obtained using various approximation criteria, and the experimental one. PMID- 2251424 TI - [Photon or electron irradiation of the internal breast lymph node chain. Experimental dosimetry and clinical implications]. AB - The radiation therapy of internal mammary chain, according to many other authors, is indicated in patients with N + breast cancer or with inner quadrant disease. Since the direct field with gamma radiation seems to induce important adverse effects on myocardium, the authors were induced to check experimentally dose distributions of 12-15 MeV electron beams and compare the results to gamma photon dose distribution. Materials and dosimetric methods as well as experimental results are described. Moreover theoretic and practical point of view are discussed coming to the conclusion that electron beams are more suitable for myocardial saving. Nevertheless some technical variations are required, to maintain the typical homogeneity of photon beams. PMID- 2251423 TI - [A proposal for the treatment technique for the breast and regional lymph nodes in patients with conservatively operated neoplasms]. AB - Adequate irradiation of regional lymph-nodes in selected patients seems to improve disease-free and over-all survival rates. Technically, regional lymph nodes are generally treated separately (supra-infra clavicular, apex of axilla and internal mammary chain-IMC). About the treatment of the IMC nodes, there are two main problems: the identification of the individual target volume, and its correct irradiation. For the latter problem, the most employed solutions are: the inclusion of IMC in the tangential fields, the use of the direct or oblique electron beam for IMC alone. None of them is optimal regarding to the tolerance of adjacent critical organs and from a geometric and dosimetric point of view. In this paper we propose and discuss a modified method. The IMC nodes together with the breast are irradiated by a three field technique (two tangential photon beams and one oblique electron beam). Their arrangement allows to treat every part of the target by two fields, reducing the risk of hot and cold spots. This is obtained by extending the internal tangential photon beams to cover the electron beam. Wedges and different weights must be used to achieve an uniform dose distribution. PMID- 2251425 TI - Intraoperative electron beam therapy. PMID- 2251426 TI - [Technical-dosimetric aspects of a simplified procedure for intraoperative radiotherapy with electrons. Experience at the San Raffaele Hospital of Milan]. AB - A modified IORT procedure with electron beams, used at HSR-Mi, has been illustrated. The design and the technical innovations of our IORT applicator system are presented. The dosimetric properties of this system for a variety of energies and applicator sizes are documented. PMID- 2251427 TI - [Description and results of a simplified procedure for intraoperative electron radiotherapy]. AB - In San Raffaele Institute a simplified procedure for intraoperative radiotherapy (IORT) was developed. An applicator system of "guide-containers" was used to facilitate the use of IORT (with electron beam) with different treatment fields. Application of this technique was studied; no IORT related complications was observed in phase I and clinical good results are reported. PMID- 2251428 TI - [Intraoperative radiotherapy with electrons (IORT). Dosimetry problems, first experience]. AB - In this paper, preliminary results on the IORT dosimetry performed on the two radiotherapy centers, "Regina Elena National Cancer Institute" and "S. Cuore Catholic University", are presented. The absolute dosimetry has been performed with ion chambers (ENEA chamber and Markus flat chamber) using a water phantom. The relative measurements have been performed with solid state diodes and radiographic films, calibrated on absolute dosimetry system. PMID- 2251429 TI - [Latent alveolitis in systemic disease. The transition between the normal and the pathological]. AB - Alveolitis, an accumulation of inflammatory and immune cells in the alveolar structures, is the essential anatomical lesion associated with the development of pulmonary fibrosis. Broncho-alveolar lavage enables the detection of an alveolitis in patients without any respiratory disorder but having known pathology which can frequently lead to interstitial pneumonia, (certain systemic diseases). The cellular analysis of the bronchoalveolar lavage enabled two types of latent alveolitis to be identified: a lymphocytic alveolitis is very frequent during the course of extra-thoracic sarcoidosis, Crohn's disease, primary biliary cirrhosis, Sjogren-Gougerot syndrome, acute systemic lupus erythematosus and rheumatoid disease. A polymorphonuclear neutrophil alveolitis with or without an associated lymphocytosis which confirmed the almost exclusive attribute of either scleroderma, dermatopolymyositis or Sharp's syndrome. The role of alveolar macrophages is shown to be essential by the secretion of free oxygen radicals, chemotactic factor for polymorphonuclear neutrophils and for fibroblasts proliferation factors (fibronectin, fibroblastic growth factor). The significant and prognostic value of latent alveolitis remains poorly understood. A prolonged follow up of patients shows that the existence of a polymorpho-nuclear alveolar neutrophilia or of secretions containing fibronectin and free oxygen radicals from the alveolar macrophages is associated with a progressive deterioration of respiratory function. In summary the evidence of latent alveolitis in asymptomatic patients leads to the hope that in the future early therapeutic intervention may be instituted before the development of irreversible anatomical lesions. PMID- 2251430 TI - [Respiratory history in children and asthma]. AB - The purpose of this study was to examine the relationship between asthma, the respiratory history and possible disturbances of pulmonary function in teenage asthmatics. This aetiological study was carried out in 103 asthmatics and 1094 controls who were teenagers attending schools in Bordeaux. In addition to the data collected by the teenagers using a self administered questionnaire, parents also filled out a complementary questionnaire. Spirometry was performed in a sample of 112 subjects. The result showed a significant relationship between asthma and respiratory history in childhood and infancy. Moreover there was a significant decrease of FEV1, (in girls only) and FEF 25-75 (boys and girls) amongst the asthmatic pupils. PMID- 2251431 TI - [The measurement of dyspnea]. PMID- 2251432 TI - [Symptoms and respiratory function in a group of Gruyere cheese processors in Comte]. AB - We have analysed the symptoms and respiratory function of a group of cheese processors making gruyere Comte in relation to a group of controls: 96 male cheese workers (mean age 36 +/- 11.1) and 97 controls who were of the male sex and of comparable age, height, weight and smoking habits. The cheese workers had a lower educational and professional level (p less than 0.01) and had a higher level of alcohol consumption than the controls (p less than 0.05). The prevalence of chronic bronchitis and of dyspnoea in the cheese workers (respectively 13.5 and 23.9%) was not significantly different from that in the controls (10.3 and 35%). 5 cheese workers (5.2%) were suspected of having occupational asthma; 5 (5.2%) were suspected of having hypersensitivity pneumonia (cheese workers' disease): 41 (42.7%) had signs of conjunctivitis during work, of whom 30 occurred only in the hot cellars. The respiratory function parameters measured were identical in the two groups (vital capacity, FEV1, mean expiratory flow at 25% and 75% of vital capacity). In conclusion, evidence of allergic problems (asthma, hypersensitivity pneumonia and conjunctivitis) seems to be frequent in refiners of Comte but the cases identified need to be confirmed; cheese refiners of Comte do not seem to have any particular risks of chronic bronchitis and of alteration of respiratory function. PMID- 2251433 TI - [A visual analog scale of exercise dyspnea]. AB - We have adapted a visual analogue scale (VAS) to make repeated measurements of the sensation of dyspnoea during an exercise test on a bicycle ergometer. We tested the reproducibility of the development of the VAS as a function of work load and its sensitivity in detecting changes in the sensation of dyspnoea induced by the addition of an inspiratory resistance or by a trial of oxygen administration in 13 patients who were dyspnoeic on effort. The reproducibility was acceptable providing to perform a preliminary test and to eliminate the rare subjects who was incapable of performing the test (1/13). The method turned out to be equally sensitive as to the effect of inspiratory resistance for 8/12 patients and for the oxygen enrichment of inspired air for 8/9 patients. This scale thus provides a reproducible and sensitive estimation of the sensation of dyspnoea during effort and thus appears valuable in evaluating the subjective response in therapeutic trials in patients who are dyspnoeic on effort. PMID- 2251434 TI - [Childhood asthma and sports in school: a survey of teachers of sports and physical education]. AB - Exercise induced bronchial obstruction is very common in asthmatic children who represent at least 5% of the general paediatric population. 89 teachers of physical education at school replied to a questionnaire on asthma: 82% knew the existence of exercise induced asthma, all thought that asthmatics can do sport at school; however their knowledge of this disorder seemed insufficient to offer sporting activities in a satisfactory manner; the idea of asthma as a psychological disorder is well ingrained (61.6%), they felt that necessarily the bronchial obstruction should be noticed by the asthmatic (58%) and finally a significant proportion (29%) thought that they had never seen a child in an asthmatic crisis during their lessons. The majority (88%) were favourable to information on asthma given by an information film followed by a discussion. PMID- 2251435 TI - [Pneumopathy caused by methotrexate]. AB - Methotrexate, an antifolate cytotoxic drug, is used in anticancer chemotherapy as well as an immuno suppressive in rheumatoid arthritis. It is responsible for numerous secondary effects, amongst which is a characteristic acute pneumonia known since 1969. This pneumonitis has been described in detail, up to the present time in 78 cases gathered in this review. The prevalence of this complication is estimated at around 7%. This pneumonia may occur whatever the age, indication for which methotrexate is prescribed, the route of administration of the product (including the intra-thecal route) and the dose. It includes dyspnoea, fever, (sometimes quite marked) and frequently an acute reversible respiratory failure. Radiologically the opacities are usually diffuse interstitial and symmetrical with a basal predominance with sometimes some confluence and occasionally a pleural reaction. In a small number of cases a transient mediastinal adenopathy has been described. Respiratory function tests show a rapidly developing restrictive syndrome accompanied by hypoxia and hypocapnia. Broncho-alveolar lavage is characterised by hypercellularity with a frank and apparently transitory lymphocytosis. Histologically the most frequent lesion sighted is an extensive acute granulomatous reaction with or without oedema. Most often the outcome is favourable (75% of cases). However 6 deaths due to respiratory failure have been reported. Even though there has not been any formal test, steroid therapy in high dosage seems to accelerate recovery. Progress to an irreversible pulmonary fibrosis is possible but rare. The mechanism of this drug related acute pneumonia is not known but would seem to resemble that of other granulomatosis. Besides this rapidly progressive pneumonitis, methotrexate is responsible for a very small number of cases of severe pulmonary oedema and of acute painful pleurisies. PMID- 2251436 TI - [Practical diagnostic approach to anomalies of the aortic arch. Apropos of 31 pediatric cases]. AB - This analysis of 31 cases of anomalies of the aortic arch has confirmed the predominance of subclavian retro-oesophageal arteries and double aortic arches (74% of cases). The age at which the first clinical signs presented was less than one year in 75% of cases. Respiratory signs predominated with recurrent bronchitis (16 cases) and bronchial congestion (9 cases). These signs were not specific for the type of aetiology and were characterised by their chronicity and recurrent nature. Inspiratory and expiratory stridor was found on 8 occasions and was very suggestive of the diagnosis. There was a frequent association of asthma and anomalies of the aortic arch in this series (13 cases) with 6 cases of atopic asthma in early childhood and 7 cases of asthma in infancy. The oesophago gastroduodenal transit was the key diagnosis which enabled the vascular anomaly to be confirmed. There was, however, a failure on 5 occasions with 2 false negatives and 3 cases where the wrong type was suspected. Fibreoptic bronchoscopy enabled the topography to be established more precisely including the degree of compression (in 14 cases) and showed evidence of associated tracheomalacia in 7 cases. Nuclear magnetic resonance was very helpful, giving a better definition of the anatomical type and of the relationship of the vascular arch with the oesophago-tracheal axis. Broncho-fibroscopy and nuclear magnetic resonance make strong contributions towards the indications for operation. PMID- 2251437 TI - [The bronchodilator effect of aerosol beta-2-mimetic and anticholinergic agents in patients with chronic bronchitis]. AB - The aim of this study was to compare the effects of beta-2 stimulant adrenergic bronchodilators, salbutamol (S) and atropinic bronchodilators, oxitropium bromide (O). The drugs were administered by aerosol, alone or in combination. 20 patients with stable chronic bronchitis were randomised into two groups G1 and G2 and respiratory function tests were done on each group in two sequences, S1 and S2 with 24 hours between. The sequence S1 consisted of three spirometric measurements; an initial control measurement (C) preceding the inhalation of two puffs of 100 mcg of S with a repeat spirometry 15 minutes later followed by the inhalation of two puffs of 100 mcg of O followed by a final spirometry 45 minutes later, one hour after beginning the test. The protocol S2 was similar but the order of drugs was reversed (O then S). The subjects were subjected successively to regimes S1 and S2 for group 1 and inversely for group 2 according to the standard procedure for a crossover trial. The forced expired volume (FEV1) was expected as a percentage of the predicted values and absolute values. Thus only the first dose of inhaled bronchodilator increased slightly but significantly the FEV1. In effect, the administration of the second product led to no supplementary bronchodilator effect. The patients were classified as responders or non responders for different thresholds of improvement of FEV1 of 10, 15 and 20%. The number of non-responders to the 2 classes of drugs was much greater when the threshold of improvement was raised to 20%. Some patients responded to bronchodilators, others uniquely to one of the two products and finally some to neither. Without reversibility tests it is not possible to predict the response to atropine from the response to beta-2-mimetics. PMID- 2251438 TI - [Steroid-sensitive cavitating pulmonary opacity in Horton's disease]. AB - We report the case of a 72 year old woman treated for seven months for Horton's disease presenting with a cavitating pneumonia of the left axillary segment associated with a deterioration of the general state, at the time of which the steroid therapy was in the course of being decreased. The radiological appearance and the clinical context of immune depression had led to a trial of a quadruple anti-tuberculous therapy in spite of the absence of any bacteriological proof. This rapid aggravation of the condition under treatment led to the suggestion of a pulmonary localisation of Horton's disease. The rapid regression of the lesions after increasing the dose of steroids and the negative cultures on Lowenstein medium pleaded in favour of this hypothesis. However the continuation of anti tuberculous treatment seems justified in such cases in so far as the diagnosis of Horton's disease of the lung often cannot be maintained other than retrospectively in the absence of histological proof. PMID- 2251439 TI - [Favorable outcome of Wegener's disease limited to the lungs. Apropos of a case]. AB - A case of Wegener's granuloma limited to the lungs is reported in a 22 year old man. The pulmonary radiograph showed bilateral nodules. A lung biopsy of a nodule revealed a necrosing vasculitis involving the arteries and the veins and some areas of necrosis in geographical contours around these vessels. The renal function was normal and 4 1/2 years later the outcome remains favourable with the minimum of treatment, the exception being a course of antibiotics post operatively. Fifty seven cases of Wegener's granuloma limited to the lungs have been diagnosed after lung biopsy, transbronchial or bronchial material. The outcome was favourable in 72% of cases. This result was observed in the absence of any treatment in 6 cases (13%). In 2 cases the pulmonary nodules disappeared or developed cavities. In 4 cases the anatomical and/or radiological progress is unknown. Currently the factors leading to such an outcome have not yet been identified. PMID- 2251440 TI - [Multiple basocellular epitheliomas of the back after repeated radiologic tests]. AB - The authors report the observation of multiple epitheliomas of the back in a patient submitted to numerous radiological examination forty years earlier. They recall the likely risk of the appearance of these cutaneous tumours after this type of exposure. PMID- 2251441 TI - [Pleural fibroma: apropos of a case]. AB - The authors report a case of a pleural fibroma occurring in a 72 year old woman. The tumour presented with both an osteoarthropathy and hypoglycaemia. An X-ray revealed an abundant associated pleural effusion. Immune studies were positive for the presence of vimentin and negative for keratin, as occurred in this case, were in favour of a pure fibroblastic origin for these tumours. PMID- 2251442 TI - [Plasma cell granuloma. Report of a case]. AB - The authors report a case of plasma cell granuloma of the lung, an inflammatory tumour occurring in a young Egyptian aged 23 without any history of chest diseases. The patient had had three weeks before his hospital admission light haemoptysis and associated with weight loss. The diagnosis was made on a bronchial biopsy. Thus a diagnosis could be made without recourse to surgery because of the occurrence of bronchial invasion. No aetiological factor was found to explain the pathogenesis of the granuloma. PMID- 2251443 TI - [Cervico-mediastinal inflammatory pseudotumors due to esophageal perforation by foreign bodies]. AB - Two patients suffered from superior mediastinal masses producing pain and dysphagia. They were investigated using imagery and endoscopy without a definite diagnosis being made. It was finally decided to perform a cervical exploration in both cases and this enabled a diagnosis of perforation of the oesophagus and pseudo-tumoral abscess to be made. The foreign body responsible was found in one case. The symptoms and signs of oesophageal perforation by foreign body may be misleading when they are chronic or delayed. There remains a place for surgical exploration when other methods have failed. PMID- 2251444 TI - Aetiology of duodenal ulcer. AB - Epidemiological evidence indicates that duodenal ulcers are caused by environmental ulcerogens, although the nature of these ulcerogens has not yet been defined. It is not known whether individuals who develop an ulcer do so because they are uniquely susceptible to the ulcerogens or whether the ulcerogenesis is a chance event. It seems that the main abnormality underlying duodenal ulceration relates to failure of normal healing, as reflected by chronicity and tendency to recurrence. It is not yet known whether there is failure of the repair processes, or interference with the processes involved in normal mucosal repair. PMID- 2251445 TI - Recent concepts in bile formation and cholestasis. AB - Progress has recently been made in the understanding of normal bile secretion mechanisms. The membrane carriers for bile acids have been identified and new insights into intracellular transport mechanisms have been obtained. In particular, characterization of a vesicular pathway involving the Golgi apparatus is well under way. Hypercholeretic bile acids, such as ursodeoxycholic acid, have been discovered. Their choleretic effect is far greater than that of physiological bile acids and they stimulate bicarbonate secretion. Testable hypotheses to explain their hypercholeretic effect have been proposed, in particular the chole-hepatic shunt hypothesis. Several mechanisms capable of inducing cholestasis have been identified: a) inhibition of Na+, K(+)-ATPase; b) increased permeability of the paracellular pathway leading to leakage of bile constituents back into plasma; c) microtubule or microfilament dysfunction; d) increased cytosolic free calcium concentration due to permeabilization of the endoplasmic reticulum calcium stores. It is not yet possible, in a given case, to establish which of these mechanisms is predominant. Several may operate. A better knowledge of the mechanisms involved may lead to improved treatment. PMID- 2251446 TI - Destructive intrahepatic bile duct diseases. AB - This paper reviews cholestatic liver diseases which are characterized by disappearance of the intrahepatic bile ducts ("vanishing bile duct" diseases). In neonates and children, the most important entities are extrahepatic bile duct atresia and paucity of intrahepatic bile ducts, including syndromatic and nonsyndromatic varieties. Immunological mechanisms play a role in the bile duct obstruction observed in primary biliary cirrhosis, graft-versus-host disease and chronic liver transplant rejection, and possibly also in primary sclerosing cholangitis and sarcoidosis with chronic intrahepatic cholestasis. Idiopathic adulthood ductopenia represents a newly defined entity, the nature of which remains unclear. Mention is made of recently reported forms of intrahepatic bile duct destruction due to toxins and drugs (iatrogenic cholangiopathies). New insight into the pathogenesis of these diseases has been brought about by progress in immunology, imaging techniques of the liver and hepatobiliary surgery. PMID- 2251447 TI - [Indications and limitations of the surgical treatment of portal hypertension]. AB - The authors report a review of the literature and describe their personal experience with treating esophageal varices; all types of surgical approaches (selective and total shunts, esophageal transection) are examined and compared to the results obtained with non surgical treatment (particularly endoscopic sclerotherapy). Indications and results of surgical treatment are discussed from three definitive viewpoints: prevention of first bleeding or prophylactic treatment, control of acute bleeding or emergency treatment and prevention of rebleeding or elective treatment. PMID- 2251448 TI - Liver steatosis: recent advances. PMID- 2251449 TI - Controversies on terminology, definition and morbid significance of gastric and duodenal erosions. PMID- 2251450 TI - [Changes in mechanical and functional processes of the lower esophageal sphincter in patients with reflux esophagitis]. AB - The present study was performed to establish eventual inferences of functional and mechanical alterations of the lower esophageal sphincter (LES) in determining reflux esophagitis. The LES basal pressure, the percentual incidence of the incoordinate LES relaxations swallowing-induced, the LES overall and abdominal length, with gastroesophageal reflux disease (GERD), with and without endoscopic evidence of esophagitis, were manometrically evaluated in 117 consecutive patients. In patients with symptomatic GERD, a significant LES pressure reduction, which is inversely related to the severity of the endoscopic mucosal damage, an increased prevalence of the incoordinate LES relaxations swallowing induced and, only in patients with esophagitis, a significant reduction of the LES overall and abdominal length of the LES, were showed. Two or three alterations of the LES antireflux devices can occur in the same patient, thus increasing the risk of esophagitis. PMID- 2251451 TI - [Clinical characteristics of 153 patients with Crohn's disease. Presentation of a Turin case series]. AB - This clinical and epidemiological retrospective study of 153 Italian Crohn's disease patients, surveyed between 1965 and 1988 took into account the following features: male to female ratio; region of origin; familiarity; age at onset; anatomical site of lesions; symptoms at onset; diagnostic delay; local and general complications; relapses; admissions; surgery and mortality rates. The clinical patterns of 67 patients surveyed between 1965 and 1977 (group A) were compared with those of 86 patients observed from 1978 to 1988 (group B). Overall results agreed with those of the literature, except for a male prevalence and a longer diagnostic delay. As compared to group A, group B showed: a) a higher number of females; b) a statistically significant increase (p less than 0.001) of patients from Southern Italy, thus supporting the hypothesis of a role of environmental factors in the onset of the disease; c) a reduced surgery rate, in agreement with the general trend of a more cautious surgical approach in Crohn's disease. PMID- 2251452 TI - [Failed dissolution of a gallstone by methyl tert-butyl ether: importance of predicting gallstone chemical composition]. AB - In December 1986 we attempted direct chemical litholysis using methyl-tertiary butyl-ether (MTBE) in a sixty-year-old man with severe ischemic heart disease who had suffered frequent episodes of biliary colic due to a radiolucent gallstone. MTBE was infused for a total of 17 hrs over a period of 5 days; however the gallstone diameter remained unchanged. The patient was subsequently cholecystomized and chemical analysis revealed that the gallstone was a pigment stone. The need for accurate prediction of gallstone composition before beginning an invasive, such as MTBE infusion, is emphasized. PMID- 2251453 TI - Multiple mucosal gastrointestinal metastases from primary asymptomatic bronchogenic carcinoma. AB - Gastrointestinal metastases from bronchogenic carcinoma are considered very unusual. We report a case of a 62-years-old man with a primary asymptomatic bronchogenic carcinoma who developed symptomatic multiple mucosal metastases to gastrointestinal tract. The following case is presented to draw attention to the unusual clinic presentation with a variety of differential diagnostic considerations. PMID- 2251454 TI - [Clinical importance of echographic screening of the entire abdomen]. AB - Unsuspected abnormalities are occasionally detected during real-time examinations. To determine the frequency of such findings detected during the standard ultrasound examination of the entire abdomen, the records of 765 consecutive patients were reviewed. A significant number of occult abnormalities were detected: approximately one-fourth of all abnormalities were found in the abdominal survey. The influence of the abdominal survey on the clinical management and improved radiological consultation are discussed. PMID- 2251455 TI - Surgery and chemotherapy in the treatment of gastric non-Hodgkin's lymphoma. AB - We have retrospectively examined 35 cases of non-Hodgkin's lymphoma (NHL) with gastric involvement at the onset. All patients have completed induction therapy at the time of this report. Histologic specimens have been classified according to the Working Formulation. Patients have undergone surgery and/or chemotherapy. Twenty out of 22 patients with stage I or II disease had surgery. Seventeen out of 20 gastrectomized patients achieved complete remission (11 with stage I and 6 with stage II): Fifteen of these are in their first complete remission with median follow-up of 24 months (range 8-68). Three patients with stage IV had surgery, two of which achieved CR. These data confirm that combined therapy is useful in gastric NHL presenting with stage I and II; no conclusions can be drawn regarding disseminated disease. PMID- 2251456 TI - [The duodenum and non-steroidal anti-inflammatory agents]. AB - We have carried out a longitudinal study in order to confirm our preliminary data on the heavier involvement of the duodenum compared to the stomach after non aspirin non-steroidal anti-inflammatory drugs (NSAIDs). 53 patients with upper digestive haemorrhage due to recent intake of NSAIDs without preexisting known peptic pathology -28 p. from aspirin and 25 p. from NSAIDs other than aspirin- were selected. Aspirin and its derivatives mainly affected gastric mucosa whereas non aspirin NSAIDs the duodenum. 42 of these patients have been observed for two more years; independently of the treatment, ranitidine 150 mg daily vs antacids if needed, the annual rate of recurrence has been very low. These findings have further confirmed the accurate selection of our patients without previous peptic pathology (in this case the rate of recurrence would have been much higher) and also suggest a more rational diagnostic and therapeutic approach to these patients. We then observed a consecutive series of 107 patients affected with duodenal ulcer bleeding: 51 by NSAIDs and 56 not by NSAIDs; both groups were given H2-antagonists and blood transfusions if needed. The short term prognosis has been rather positive mainly for the NSAIDs group, in which no mortality has been observed, independently of the number of blood transfusions and length of hospitalization. In our experience the high percentage of NSAIDs duodenal ulcers (about 50%), shows an increase of this pathology, less severe than peptic one, even if expressed by a serious event as digestive bleeding. It is our opinion that these percentages and prognostic evaluations should be considered in therapeutic decision, limiting thus surgical and aggressive endoscopic procedures. PMID- 2251457 TI - [Acute pancreatitis and uremia: what is their pathogenetic relationship? Description of a case observed during hemofiltration]. PMID- 2251458 TI - [What is your diagnosis? Antero-lateral repolarization disorder]. PMID- 2251459 TI - [Strategy in sonographic suspicion of a parasitic disease of the liver (echinococcosis and amebic abscess)]. AB - Ultrasonography is a widely used, early available and well established method in the examination of abdominal symptoms. The strategy for investigation of focal liver lesions, suspected to be parasitoses of the liver (echinococcus cysts or amebic abscess) is shown. The ultrasonographic morphology of echinococcosis and amebic abscess is characteristic, although it is imperative to distinguish these lesions from other tumorous or cystic lesions. The diagnosis suspected through case history and clinical appearance is confirmed by modern serological tests in 90 to 95% of echinococcosis and in 95 to 100% of amebiasis. Fine-needle aspiration guided by ultrasound is indicated in cases of a negative serological result in order to exclude a pyogenic abscess. This evaluation allows a fast diagnosis and efficient therapy. PMID- 2251460 TI - [Surgical aspects of focal pancreatic lesions]. AB - Focal lesions of the pancreas or its surroundings comprise a variety of morphologic substrates that do not always require treatment. Cysts and neoplasms are the two important groups. Postpancreatic cysts are increasingly and successfully treated by endoscopy and interventions guided by ultrasound. They have to be distinguished from cystic neoplasms or intracavitary hemorrhage which have to be approached by primary surgery. Pancreatic malignancies do not necessarily invite to a fatalistic attitude. Only ductal pancreatic cancer carries a still poor prognosis although we have achieved a 20% 5 year survival rate if resection without residual tumor was possible. If lymph nodes were not involved 43% of patients survived for 5 years. Periampullary carcinoma and the other pancreatic neoplasms carry a much better prognosis. The search for focal pancreatic lesions must be particularly thorough in patients presenting with diabetes of sudden onset, persistent hyperamylasemia and in some cases with an acute, possibly severe pancreatitis without apparent cause and an age of over 40 years. PMID- 2251461 TI - [Lymphocytic gastritis]. AB - Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the epithelium of the gastric mucosa. This form accounts for 4.5% of chronic B gastritis and manifests itself by dyspepsia, anorexia and weight loss. The course is benign, as 12 of 19 patients recovered within 24 to 36 months in Haot's studies. Macroscopically it appears with nodules, erosions, thickened mucosal folds, or diffuse varioliform pattern. The gastric corpus is preferentially involved. The etiology is unknown. Some authors have hypothesized an abnormal immune response to a local antigen, i.e. Campylobacter pylori. PMID- 2251462 TI - [Ultrasonically-guided sclerosing of kidney and liver cysts using polidocanol]. AB - First experiences are reported with percutaneous sclerosing therapy of cysts with polidocanol (aethoxysklerol 1%) using ultrasound for needle guidance. They cover two patients with symptomatic cysts of the liver and a patient with polyglobulinemia and an erythropoietin-producing renal cyst. These experiences are compared to previously reported ones. PMID- 2251463 TI - [Endoscopic treatment of bile duct stones and their complications]. AB - Endoscopic treatment of bile duct stones has reached a high degree of perfection by the introduction of adjuvant therapies raising the rate of success while at the same time reducing risk. Large stones are fragmented mechanically or by means of extracorporal shock wave lithotripsy thus permitting to avoid a long and risky papillotomy. Drainage of the bile is assured with a nasobiliary drain in case of primary failure reducing the risk for cholangitis. Endoscopic treatment is the choice for residual or recurring stones after cholecystectomy and for severe purulent cholangitis in which surgical treatment is still charged with a high mortality. Endoscopic stone removal is further indicated when an operation per se carries a high risk. Long-term studies have demonstrated that even patients in which the gall bladder is preserved stay free of recurrence. In patients with severe biliary pancreatitis early papillotomy reduces complication-rate and mortality. The question remains unsettled whether patients at normal risk with simultaneous cholecysto- and choledocholithiasis should undergo direct cholecystectomy and bile duct revision or if they could profit from endoscopic removal of stones prior to cholecystectomy. PMID- 2251464 TI - IgE-positive mast cells on the human nasal mucosal surface in response to allergen exposure. AB - IgE-bearing mediator cells are suggested to be the effector cells in type I allergic rhinitis. These cells can be demonstrated by their granular constituents or by the surface-bound IgE antibodies. We developed immunohistochemical techniques in order to stain the cell-bound IgE using polyclonal or monoclonal anti-human IgE antibodies. These techniques can be applied to nasal biopsies as shown previously or to cytospin specimen harvested by a brush method. They deliver excellent staining results with well-preserved morphological details. Brush samples were taken from 24 grass pollen allergic subjects before season, after a nasal allergen provocation and two weeks after the onset of season. There was a statistically significant increase in toluidine blue positive and IgE positive cells 24 hours after nasal provocation (app. 12-fold, p less than 0.05) and more pronounced within the season (app. 58-fold, p less than 0.001) compared to preseasonal values. These cells appeared to be mast cells rather than blood basophils judged by morphological criteria. There was a striking correlation between the number of toluidine blue cells and that of IgE-positive cells (r = 0.98). The number of eosinophils also increased due to the seasonal allergen exposure (p less than 0.001), but less pronouncedly compared to the mast cells. These data re-emphasize the migration of IgE-bearing mast cells and eosinophils into the epithelial lining of the nasal mucosa due to allergen interaction and point to a possible role of mast cells as a carrier for IgE-molecules. PMID- 2251465 TI - Septum dislocation in the newborn: a long-term follow-up study of immediate reposition. AB - A report on the late outcome of reposition performed for septal dislocation present at birth. 42 cases have been examined 13 to 16 years after the intervention and it has been found that in the majority of patients (69%) the final esthetic and functional results have been satisfactory. Conversely, those cases (31%) where uni- or bilateral obstruction was still present at the time of late control had experienced a markedly increased incidence of upper respiratory infections. The different situations present at birth are indicated and it is stated that cases which tend to recur after repositioning requiring a second intervention and--possibly--unilateral packing are more likely to have an unsatisfactory late outcome. PMID- 2251466 TI - Nasal allergy in medical students. AB - The incidence of nasal allergy in medical students was studied in our University from 1983 to 1987. Intradermal skin tests were performed using six allergens: house dust (HD), ragweed, Japanese cedar, orchard grass, candida and broncasma berna. 154 out of 471 students (32.7%) had symptoms indicative of nasal allergy. HD and Japanese cedar were the main allergens and their positive rates were 66.4% and 51.0%, respectively in symptomatic cases. However, 34.4% of asymptomatic students also showed positive reactions to HD and 19.6% to Japanese cedar. In nasal provocation tests, 53.8% of symptomatic students who reacted positively to HD skin test showed positive reactions, while even 34.8% of asymptomatic students also showed positive reactions. The same results were obtained for Japanese cedar. It seemed that some asymptomatic students who had positive reactions to skin tests have latent allergies. A long-term follow-up would be necessary for these cases. PMID- 2251467 TI - Blood flow and pulse amplitude in the mucosa of the human maxillary sinus in relation to body posture. AB - The paranasal sinuses are non-collapsible ventilated gas pockets without any known function. They should, however, be adequately ventilated to stay healthy. Persons lying in a recumbent body position compared to persons sitting or standing upright have reduced antral mucosal blood flow, a reduction of 35%, and a congested mucosa which reduces both the mucosal gas exchange and the perostial ventilation, creating a more anaerobic antral gas mixture facilitating pathogenic bacterial growth and reduced ciliary activity. It is, therefore, recommendable for patients with sinusitis to treat themselves or be treated in an upright or semi-recumbent body position. PMID- 2251468 TI - CT-scan study of the incidence of sinus involvement and nasal anatomic variations in 196 children. AB - CT-scan was used to examine rhinosinusitis in the developing sinuses; 196 children aged from 3 to 14 years were selected on the base of their chronic rhinorrhea, nasal congestion and cough. The patients were subdivided into six age groups (3-4, 5-6, 7-8, 9-10, 11-12 and 13-14 years). In the youngest age group, the authors noted maxillary involvement in 63%, ethmoidal involvement in 58%, and even sphenoidal sinus involvement in 29% of the children. Involvement decreased gradually with age, with 10% of ethmoidal and 0% of sphenoidal involvement in the 13-14 years age group. Maxillary sinusitis, however, persisted very frequently in the oldest age group (65%). Frontal involvement seems to become significant at the age of 7-8 years (7%) but it never exceeds 15% (11-12 age group). Septal deviations occurred in 16% of the youngest up to 72% in the oldest age group. The prevalence of bullous conchae increased with age too, although less prominently. PMID- 2251469 TI - The influence of palato-cranial base (basomaxillary) angle on the length of the caudal process of the nasal septum in man. AB - The authors investigated and defined the relationship between the length of the caudal process of the quadrangular lamina and the palato-cranial base (basomaxillary) angle. The length of the caudal process was measured by an indirect method during surgical exposure in 71 patients with nasal septum deformity. The usual cephalometric reference points were used to form the angle reference lines; the points were marked over X-rays and traced on transparent paper using the "against the light" technique. It was found that the caudal process was longer than 3 cm (range 3.1-4.2 cm, mean value 3.45, standard deviation 0.34) when there existed a palato-cranial base angle; contrary, it was always shorter than 3 cm (range 1.9-3.0 cm, mean value 2.40, standard deviation 0.33) when the reference lines were parallel. That means that the angulation between the reference lines assigning the angle predisposes a longer caudal process, making possible a backward growth of this cartilaginous baton, and therefore the occurrence of some particular types of septal deformities. Finally, the authors suggest another name for the palato-cranial base angle, i.e. the basomaxillary angle, because it is simpler, shorter and still clear enough. PMID- 2251470 TI - Assessment of nasal obstruction. A comparison between rhinomanometry and nasal inspiratory peak flow. AB - In several conditions objective assessment of nasal obstruction would be of great value. In this study we have compared two different methods for this purpose. Anterior rhinomanometry is a well established method, which measures nasal airway resistance (NAR). This was compared with nasal inspiratory peak flow (NIPF) measured with a Youlten peak flow meter. The assessments were undertaken in patients with allergic rhinitis, before and after challenge with hyperosmolar saline solution. After challenge there was a fall in NIPF value as a mean of 17.4%, that was mirrored by a rise in NAR of 15.6%. There was also a statistically significant negative linear correlation between these two methods (p less than 0.01). We conclude that NIPF is a cheap, easily performed and quick method suitable for assessing nasal airway patency in e.g. allergics during treatment and during challenge. PMID- 2251471 TI - The postoperative nasal dressing. A new intranasal splint. AB - A new intranasal dressing is presented, which helps avoid discomforts caused by intranasal packings. The splint, made of polypropylene, is introduced into the nasal cavity folded like a tent, achieving a good readaptation of the mucosa and permitting breathing immediately after surgery of the septum. PMID- 2251472 TI - Aneurysmal bone cyst of the maxilla. A case report. PMID- 2251473 TI - [Neurosyphilis 1982-1989]. AB - We report the signs, symptoms, serological and CSF findings in 27 patients with syphilis and inflammatory involvement of the central nervous system. In 24 patients the neurosyphilis was symptomatic. Most patients did not report previous signs of early syphilis. A CSF pleocytosis was present in 25 patients (greater than 90%) and the CSF VDRL was reactive with a titer of 1:2 or above in 19 patients (70%). The symptomatology seemed not to be atypical for neurosyphilis although a precise classification was often not possible and the diagnosis was seldom suspected on clinical grounds. In most patients the clinician can monitor the effectiveness of antibiotic therapy by simple laboratory parameters which reflect the activity of the inflammatory process. It is disquieting, however, to note how inconsistently this follow-up was performed. PMID- 2251474 TI - [Spontaneous pneumomediastinum]. AB - We report two cases of spontaneous pneumomediastinum, typically occurring without trauma. The findings disappeared without treatment. The clinical presentation, pathophysiology, diagnosis and treatment are reviewed. PMID- 2251475 TI - [Magnetic resonance angiography. Work in progress]. AB - Rapid progress has been made in the development and clinical application of magnetic resonance (MR) techniques for creating angiogram-like images of blood vessels. Combinations of techniques such as gradient-echo pulse sequences and flow compensation (bright blood imaging) or presaturation (black blood imaging) permit the signal intensities of moving spins to be altered, so as to generate contrast between flowing blood and stationary tissues. Postprocessing of the images allows the creation of projection angiograms, which show the vasculature in a large slice of the body. Preliminary studies suggest a variety of potential clinical applications, including intracranial arteriovenous malformations and aneurysms, carotid artery disease, portal hypertension, renal artery stenosis, peripheral arterial disease and venous thrombosis. At present, MR angiography is not directly competitive with conventional contrast angiography because of lower spatial resolution and loss of signal from flow turbulence and from slow flow. Nonetheless, it is proving to be a useful clinical tool for the investigation of vascular pathology involving the head and body. PMID- 2251476 TI - [Concerning "risks and benefits of long-term treatment with estrogens" by T.M. Mack and R.K. Ross, Schweiz. med. Wschr. 1989; 119:1811-1820]. PMID- 2251477 TI - [Ovarian carcinoma: current therapeutic aspects. A review]. AB - Ovarian cancer is the leading cause of gynaecologic cancer death and the fourth most frequent cause of cancer death in women. 70% of all ovarian cancers will be diagnosed only at an advanced stage of the disease despite the improvements in diagnostic tools. Standard therapeutic concepts and new therapeutic modalities are discussed. Staging laparotomy with cytoreductive surgery is the most important part of initial patient management. Second-look operation has recently come under criticism, as it probably offers only minor therapeutic benefit. However, it remains the golden rule for evaluating different therapy modalities in the setting of a clinical trial. After surgery, chemotherapy is indicated for all patients with ovarian cancer FIGO stage III and IV. The question whether all patients with stage I and II disease need additional treatment remains unresolved. The standard regimen for patients with advanced ovarian cancer consists of six months' chemotherapy with a combination of cisplatin and an alkylating agent. Current cisplatin containing regimens achieve a clinical response rate of 60-80% and a documented pathologic complete response rate of 30% overall. Despite higher overall response rates and increased disease-free survival rates with cisplatinum combinations, long term survival is not significantly altered. Investigative approaches with intraperitoneal chemotherapy, biologic response modifiers and drug resistance modifiers may open new therapeutic avenues for this challenging disease. Radiotherapy (open field technique) also represents a highly active and curative treatment modality for certain ovarian cancer patients. Nowadays radiotherapy is mainly used as adjuvant treatment for patients with low risk early stage disease and as consolidation treatment for patients with complete remission after chemotherapy and second-look operation. PMID- 2251478 TI - [Eosinophilia-myalgia syndrome following administration of a L-tryptophan preparation]. AB - An unusual new syndrome of eosinophilia and myalgia linked with the ingestion of L-tryptophan has recently been recorded in the USA. Some of the cases were lethal. In this report we describe a severe case of eosinophilia-myalgia syndrome observed in a woman in Switzerland who fortunately recovered after one and a half years' duration. Thus far it is not clear if L-tryptophan or a contamination of the tryptophan is the cause of the syndrome. PMID- 2251479 TI - [The prehospital phase of acute myocardial infarct and its significance for thrombolytic therapy]. AB - Early thrombolytic therapy has become the treatment of choice for acute myocardial infarction (AMI). Of 189 patients admitted with AMI to the CCU of Berne University Hospital in 1988, only 17 (9%) underwent thrombolytic treatment. 101 patients (53%) were admitted within 4 hours after onset of symptoms. Early arrival (less than 4 hours) was significantly more frequent among patients admitted without prior medical consultation (76%, p less than 0.001), patients less than 65 years of age (67%, p less than 0.001), patients sustaining AMI outdoors (74%, p less than 0.005) and patients without a history of typical angina (71%, p less than 0.05). In all subgroups analyzed more than half of the prehospital delay (2.8 hours) was due to the patients' indecision whether to seek medical help; prehospital consultation by a general practitioner took 66 minutes and transportation arrangements 30 minutes; in-hospital delay from admission to intensive care treatment amounted to 72 minutes (39 minutes for arrival less than 4 hours; all median times). Overall in-hospital mortality was 16.6%. Mortality during a follow-up period of 4-16 months (overall 8.4%) was higher for patients with reinfarction (15.2%, p less than 0.05) and patients arriving with a delay greater than 4 hours (12.5%, p = 0.08). Combined mortality was 25% among 172 conservatively treated patients vs 0/17 among patients undergoing thrombolytic treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251480 TI - [Toxicomania: death beyond risk. Analysis of cause-of-death in drug addicts]. AB - Violent deaths are of considerable importance among young adults, since they account for half the deaths in this age group (average age 26.4 years). Suicide and accidents (both categories including drug overdoses) are the most frequent categories of deaths from non-natural causes, while in the USA deaths by homicide are also of considerable importance. Current repressive policies have not brought the problem of drug addiction under control. Each year deaths by overdose among drug abusers occur. Nevertheless, 40% of deaths among drug addicts are from other causes, principally accidents and suicides. In the near future, AIDS may well account for the majority of deaths among drug addicts, thus adding to the mortality from overdose, both accidental and suicidal. Has the time come to reconsider the problem of drug abuse and to find radical solutions which would previously have been unthinkable? PMID- 2251481 TI - [Value of cyto-puncture and of ultrasonic-guided micro-biopsy in solid tumors of the pancreas]. AB - 43 patients (29 men, 14 women, average age 64.7 years) with a solid lesion of the pancreas underwent echography-guided cytopuncture (needle 22 G, 88 mm) associated in 11 cases with microbiopsy (needle 21 G, 150 mm). The lesions were localized in the pancreatic head (n = 27), body (n = 13) and tail (n = 3). The sensitivity and specificity of cytopuncture were 81% and 100% respectively. There were 27 true positives (26 pancreatic adenocarcinomas and one metastasis of a prostatic adenocarcinoma); 10 true negatives (5 cases of calcifying chronic pancreatitis, 3 benign endocrine tumors, 2 cases of acute pancreatitis); and 6 false negatives (4 adenocarcinomas and 2 intrapancreatic cholangiocarcinomas). There were no false positives. Microbiopsy diagnosed 5 adenocarcinomas out of 9 cases biopsied and 2 benign endocrine tumors not detected by cytopuncture. Its sensitivity was thus 56% for malignant lesions and 64% for all lesions biopsied. Its specificity was 100%. There was one (= 2.5%) complication (dissemination on the needle pathway). We conclude that echography-guided cytopuncture is a simple and effective method of diagnosing solid tumors of the pancreas. Biopsy, though of lower sensitivity, probably serves to increase the specificity of cytopuncture, in the case of benign lesions in particular. PMID- 2251482 TI - [Current aspects in the diagnosis of pulmonary infections in intensive care patients]. AB - The diagnosis of pneumonia in the ICU patient is difficult and controversial. Clinical aspects and examination of tracheobronchial secretions are often unhelpful and even misleading. Blood and pleural fluid cultures are not sensitive, while transtracheal or transthoracic aspirations are contraindicated in the ventilated patient. However, quantitative cultures of protected specimen brush samples and bronchoalveolar lavage fluid improve sensitivity and specificity of diagnosis in pulmonary infections in the ICU patient. An easy and rapid aid in differentiating infection from colonization is quantitative analysis of gram-stained specimens of bronchoalveolar lavage fluid. PMID- 2251483 TI - [The diagnosis of pneumonia in the ventilated patient]. AB - The diagnosis of ventilator-associated pneumonia is difficult to confirm because the usual clinical criteria lack predictive value. Risk factors evaluated recently serve to assess subgroups of exposed patients. Bronchoscopic bronchoalveolar lavage (BAL) or protected specimen brush, together with quantitative bacteriology, are the present method of choice for diagnosis of nosocomial pneumonia during mechanical ventilation. Nonbronchoscopic "blind" BAL catheters provide new, attractive, accurate and easy sampling techniques. This could become the technique of choice in the future. Efforts are needed to standardize diagnostic criteria, in order to allow comparisons between groups of patients or clinical trials for prevention or treatment of ventilator-associated pneumonia. PMID- 2251484 TI - [Methods in mixed ventilation: advantages, disadvantages and consequences for work of breathing]. AB - During partial ventilatory support modes both the ventilator and the patient are performing mechanical work. These modes are currently used as mechanical ventilatory support to provide a better synchronism between the patient and the machine and to avoid a complete rest of the respiratory muscles, or as modes of weaning from mechanical ventilation. Assist control ventilation allows the patient to regulate his own respiratory rate by triggering preset ventilatory cycles. Synchronized intermittent mandatory ventilation includes both controlled cycles and spontaneous breathing cycles. Lastly, during inspiratory pressure support, each spontaneous cycle is assisted by pressurization of the circuit. This latter modality alone seems efficiently to decrease the patients' breathing work while allowing complete synchronism between patient and ventilator. PMID- 2251485 TI - [Intermediate results of balloon valvuloplasty in children with congenital aortic valve stenosis]. AB - Eleven children with aortic valve stenosis requiring treatment underwent percutaneous balloon valvuloplasty instead of surgery. Three were newborns or infants and 8 were aged 2-18 years. Aortic valve gradient was 45-160 mm Hg (mean 83 mm Hg) before valvuloplasty; after the procedure the gradients ranged from 7 43 mm Hg (mean 25). One newborn with critical stenosis and associated left ventricular fibroelastosis died 48 hours after valvuloplasty. All others showed marked clinical improvement after the procedure. Main complications included permanent loss of peripheral pulses in the catheterized leg (2 cases, age 2 months and 20 months) and aortic valve regurgitation. This was estimated as moderate (++) in 2 and moderately severe (3+) in one; it was minimal or absent in the others. All patients were followed up for 3 months to 4 years. There was one recurrence of aortic stenosis, 2 years after valvuloplasty, requiring surgery. Two infants also underwent late surgery after successful valvuloplasty, one for mitral valve replacement and one for severe subvalvular aortic stenosis. In the remaining seven children the good initial result was maintained. Aortic valve gradient was estimated with Doppler at regular intervals and did not increase significantly over the follow-up period. In conclusion, balloon valvuloplasty is an alternative to open heart surgery in aortic valve stenosis in the young; both procedures are palliative. PMID- 2251486 TI - [Percutaneous mitral valvuloplasty]. AB - Since its introduction as an alternative to surgical commissurotomy, percutaneous mitral valvuloplasty (PMV) has been preformed in a wide range of patients. PMV improves valve function significantly, and provides a final valve area of 2 cm2. The quality of the results is mainly related to valve anatomy. The incidence of complications is relatively low: death 0.5%, severe mitral incompetence 4%, and left to right shunts, as assessed by oximetry 20% of which two thirds disappear during follow-up. As of now, only mid-term follow-up results are available. If the initial result is good, functional improvement occurs in most cases and re stenosis is rare. On the other hand, secondary surgery is most often necessary in case of poor initial result or severe mitral regurgitation complicating PMV. These favorable results lead us to propose PMV as the first treatment for mitral stenosis with pliable valves. On the contrary, valve replacement remains the main treatment in calcific stenosis, PMV being restricted to particular cases: mild calcification, high surgical risk or even refusal of surgery. Finally, the decision of PMV can only be taken after exclusion of contraindications: left atrial thrombosis, moderate to severe mitral regurgitation. PMID- 2251487 TI - [Coronary restenosis 6 months following transluminal atherectomy]. AB - Directional coronary atherectomy was developed to decrease the incidence of restenosis. Among the first 61 patients treated with directional atherectomy at Mayo Clinic, 50 have been considered a success. Half of the patients had had one or more previous PTCA performed on the target lesion. Patients were followed during 6 months. Coronary angiogram was performed 6 months after atherectomy or earlier if ischemia appeared. Restenosis was defined as a greater than or equal to 50% luminal narrowing or loss of greater than or equal to 50% of the initial gain. Ischemia was documented in 23 patients. Control angiogram demonstrated restenosis in 24 patients (48%). Among those 24 patients, 18 had ischemia documented during stress test or at rest, and underwent a second procedure (second atherectomy in 4, PTCA in 8 and bypass surgery in 6 patients). Neither previous procedures nor the type of vessel significantly influenced restenosis rates. CONCLUSIONS: coronary restenosis was not less frequent after directional atherectomy, than after conventional balloon angioplasty. Previous procedures or type of vessel did not influence restenosis incidence. PMID- 2251488 TI - [Congenital heart defects and abnormalities newly detected with echocardiography in adolescents and adults]. AB - In 12,576 consecutive Doppler-echocardiographic studies (DE) performed on 11,450 patients over 3 years (1987-1989), 183 newly diagnosed congenital heart abnormalities were detected in 161 patients. The age of the 161 patients (86 female, 75 male) ranged from 16 to 84 years (median 34.5). The highest incidences of pathologies were those of ASD II (29%) and VSD (11%). With decreasing frequency the following abnormalities were diagnosed: pulmonary valve disease (8%), interatrial septal aneurysms (7%), membranous subvalvular aortic stenosis (5%), anomalous pulmonary venous connections (4%), atrioventricular canal defects (4%), persistent left superior venae cavae (4%), patent ductus arteriosus (4%), aneurysms of the membranous septum (4%), and sinus venosus defects (3%). Less common findings were coarctation of the aorta (2.5%), persistent sinusoids (2.5%), arteriovenous fistulas (2.5%), congenital LV-aneurysms (2.5%), Ebstein's anomalies (1%), anomalies of the papillary muscles (1%) and RV-dysplasias (1%). Rare findings were a cor triatriatum, a tetralogy of Fallot, a partial defect of the pericardium, a pulmonic atresia with VSD, an isolated cleft of the tricuspid valve, and finally a connection of a hepatic vein to the right atrium. In conclusion, we found an incidence of 1.4% in newly diagnosed congenital heart disease in adolescents and adults undergoing DE. 32 of 159 patients (20%) were referred to surgery, while endocarditis prophylaxis was indicated in 45%. PMID- 2251489 TI - [Significance of trans-esophageal echocardiography as an adjunct to transthoracic echocardiography]. AB - We describe our experience with the first 103 patients undergoing transesophageal echocardiography at our institution. The procedure was well accepted by most patients and associated with no major complications. The clinical indications for this procedure have included endocarditis, prosthetic cardiac valve dysfunction, detection of intracardiac source of embolism, atrial septal defect and thoracic aortic dissection. Transesophageal echocardiography proved to be useful in all of these diagnostic categories, especially if standard transthoracic echocardiography did not provide a complete assessment. PMID- 2251490 TI - [Vertebrobasilar circulatory disorders. Diagnosis--pathogenesis--therapy]. AB - Disturbances of the vertebrobasilar circulation are often seen by the general physician and usually described as "vertebrobasilar insufficiency" (VBI). However, the term VBI is only a description of a syndrome and not a definitive diagnosis. It is emphasized that on therapeutic grounds the different etiologies and pathogenesis of this syndrome should be searched for carefully by adequate examination, including clinical findings, extra- and intracranial cerebrovascular doppler sonography, computed tomography, possibly intraarterial digital angiography and nuclear magnetic resonance imaging, and laboratory examinations. The usual diagnostic and therapeutic problems in managing a patient with "vertebrobasilar insufficiency" are discussed in the light of typical case reports. PMID- 2251491 TI - [Acute effects of the natural atmospheric ozone exposure on lung function of clinically normal smokers and non-smokers]. AB - The influence of moderate ambient ozone exposure on spirometric lung function and bronchial responsiveness was analyzed in 13 healthy adult nonsmokers and 11 asymptomatic smokers. The study was divided into an initial investigation at low atmospheric ozone concentrations of about 80 (range 68-102) micrograms/m3 and a subsequent similar testing at moderately elevated ozone concentrations above 140 (range 145-205) micrograms/m3. Overall there was a slight but significant impairment in forced expiratory volumes (p less than 0.002) at elevated compared with low ozone concentrations. Furthermore, a significant increase in bronchial responsiveness was shown, with a decrease in threshold dose for inhaled metacholine to produce a 50% fall in specific airway conductance (p less than 0.02). In both smokers and nonsmokers there was a similar change in lung function at ambient ozone concentrations, with more pronounced bronchial irritation in the smokers group. It is concluded that even moderately elevated ambient ozone concentrations can induce slight but significant ventilatory obstruction and an obvious increase in bronchial responsiveness in healthy adults. Although the minor impairment of lung function did not cause manifest acute respiratory problems, it still reduced maximal physical ventilation capacity. The results further support the assumption that air pollution may act as a primary trigger in the development of obstructive airway disease. PMID- 2251492 TI - [The treatment of juvenile migraine using flunarizine or propranolol]. AB - The clinical efficacy of flunarizine and propranolol for the prevention of migraine attacks was assessed in 33 children in a double blind study. After a run in phase of one month, 32 patients started the active medication. A reduction in the number of migraine attacks was observed in 75% of the flunarizine group and in 73.8% of the propranolol group. Propranolol also reduced the severity of attacks. Transient side effects were observed in 3 of 17 of the flunarizine group and in 5 of 15 of the propranolol group. The most frequent side effect was increased fatigue, which required interruption of therapy in 2 patients of the propranolol group. PMID- 2251493 TI - [Menetrier's disease: brain infarction as an unusual first symptom]. AB - A 43-year-old patient was admitted to hospital with an apoplectic stroke caused by an angiographically confirmed partial stenosis of the arteria cerebri media branch. We diagnosed Menetrier's disease, documented by gastroscopy and histology, after having eliminated other causes for the apoplexy. We suggest a direct causal relationship between the stroke and Menetrier's disease, since high incidences of thromboembolic complications have been reported in association with this rare disease. After conservative therapy with H2-blockers, laboratory values returned to normal. In the two years following diagnosis, the patient reported no recurrence of neurologic complications. PMID- 2251494 TI - [Fetal complete heart block with myocarditis and maternal SS-A-/AA-B/antibodies]. AB - We report on a newborn with fetal acquired heart block (CHB). CHB is a rare, irreversible defect, commonly occurring in conjunction with myocarditis in the neonatal lupus syndrome. Development of CHB is strongly associated with maternal anti-SS-A(Ro)/SS-B(La) antibodies. Intrauterine therapy of CHB is not possible. Concomitant myocarditis, however, can be treated effectively with dexamethasone. Mothers with an elevated risk of fetal CHB can be identified by their history (underlying systemic connective tissue disease, previous pregnancies with CHB), an immunogenetic predisposition (HLA-DR3) and analysis of the SS-A/SS-B antibody pattern. In these pregnancies prevention of CHB with plasmapheresis plus dexamethasone during pregnancy may be possible. PMID- 2251496 TI - Promotion of the human genome project. PMID- 2251495 TI - Hair analysis. PMID- 2251497 TI - Cystic fibrosis pilot projects go begging. PMID- 2251498 TI - The ethics of AIDS care. PMID- 2251499 TI - Biomechanics of mammalian terrestrial locomotion. AB - Mammalian skeletons experience peak locomotor stresses (force per area) that are 25 to 50% of their failure strength, indicating a safety factor of between two and four. The mechanism by which animals achieve a constant safety factor varies depending on the size of the animal. Over much of their size (0.1 to 300 kilograms), larger mammals maintain uniform skeletal stress primarily by having a more upright posture, which decreases mass-specific muscle force by increasing muscle mechanical advantage. At greater sizes, increased skeletal allometry and decreased locomotor performance likely maintain stresses constant. At smaller sizes, skeletal stiffness may be more critical than strength. The decrease in mass-specific muscle force in mammals weighing 0.1 to 300 kilogram indicates that peak muscle stresses are also constant and correlates with a decrease in mass specific energy cost of locomotion. The consistent pattern of locomotor stresses developed in long bones at different speeds and gaits within a species may have important implications for how bones adaptively remodel to changes in stress. PMID- 2251500 TI - The enzymic nature of antibody catalysis: development of multistep kinetic processing. AB - Detailed kinetic investigations of a catalytic antibody that promotes the hydrolyses of an anilide and phenyl ester show that this catalyst uses a multistep kinetic sequence resembling that found in serine proteases to hydrolyze its substrates, although antibody was elicited to a single transition-state analog. Like the serine proteases the antibody catalyzes the hydrolysis reactions through a putative covalent intermediate, but unlike the enzymes it may use hydroxide ion to cleave the intermediates. Nevertheless, the antibody is a potent catalyst with turnover at higher pH values rivaling that of chymotrypsin. This analysis also reveals that turnover by the antibody is ultimately limited by product desorption, suggesting that improvements in catalytic efficiency may be achieved by judicious changes in the structure of the substrate, so that it is not superimposable on that of the eliciting hapten. PMID- 2251501 TI - Dissociation of gp120 from HIV-1 virions induced by soluble CD4. AB - The CD4 antigen is the high affinity cellular receptor for the human immunodeficiency virus type-1 (HIV-1). Binding of recombinant soluble CD4 (sCD4) or the purified V1 domain of sCD4 to the surface glycoprotein gp120 on virions resulted in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41. This may represent the initial stage in virus-cell and cell cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1. PMID- 2251502 TI - Autonomous developmental control of human embryonic globin gene switching in transgenic mice. AB - The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (epsilon) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human epsilon-globin gene was linked to a 2.5 kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human epsilon globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of epsilon gene expression in definitive erythroid cells suggests that the developmental regulation of the epsilon-globin gene depends only on the presence of the LCR and the epsilon-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of epsilon-globin gene developmental control distinguishes it from the competitive mechanism of regulation of gamma and beta globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching. PMID- 2251503 TI - Sequence-specific DNA binding by the c-Myc protein. AB - While it has been known for some time that the c-Myc protein binds to random DNA sequences, no sequence-specific binding activity has been detected. At its carboxyl terminus, c-Myc contains a basic--helix-loop-helix (bHLH) motif, which is important for dimerization and specific DNA binding, as demonstrated for other bHLH protein family members. Of those studied, most bHLH proteins bind to sites that contain a CA- -TG consensus. In this study, the technique of selected and amplified binding-sequence (SAAB) imprinting was used to identify a DNA sequence that was recognized by c-Myc. A purified carboxyl-terminal fragment of human c Myc that contained the bHLH domain bound in vitro in a sequence-specific manner to the sequence, CACGTG. These results suggest that some of the biological functions of Myc family proteins are accomplished by sequence-specific DNA binding that is mediated by the carboxyl-terminal region of the protein. PMID- 2251504 TI - HIV research in the SCID mouse: biosafety considerations. PMID- 2251505 TI - A wider spectrum of spondyloarthropathies. AB - As in other diseases of undetermined etiology, the diagnosis of ankylosing spondylitis (AS) and related spondyloarthropathies (SpA) is based on clinical and roentgenographic features. The current criteria for diagnosis of some of these diseases are too restricted, and do not recognize the existence of a much wider disease spectrum. For example, radiographically detected sacroiliitis is extremely frequent in AS, but may not be an obligate manifestation, especially in early or atypical forms of the disease. Arthritis involving the axial skeleton, including the sacroiliac joints, can be present in some patients without evidence of erosive disease roentgenographically. The disease spectrum of Reiter's syndrome has also been broadened considerably, and "incomplete" forms of Reiter's syndrome are observed much more commonly than the classical triad of arthritis, conjunctivitis, and urethritis. The term "B27-associated reactive arthritis" has been used in recent years to refer to SpA following enteric or urogenital infections, and the disease spectrum includes the clinical picture of typical Reiter's syndrome. The clinical spectrum of psoriatic SpA has been better clarified. Some of the less well defined B27-associated clinical syndromes include seronegative oligoarthritis, polyarthritis, or dactylitis ("sausagelike" toes) of the lower extremities, and heel pain caused by calcaneal (and tarsal) periostitis. These and other undifferentiated SpA have been ignored in previous epidemiological studies because of the inadequacy of the existing classification criteria. The European Spondylarthropathy Study Group (ESSG) has completed a study aimed at developing preliminary classification criteria for the whole group of SpA patients, with the specific intention of encompassing patients with undifferentiated SpA. PMID- 2251506 TI - Adult-onset polymyositis-dermatomyositis: description of 25 patients with emphasis on treatment. AB - A retrospective study of 25 patients with polymyositis-dermatomyositis (PM-DM) is analyzed with special attention to the effects of therapy and follow-up. All patients (100%) complained of muscle weakness and 68% of these demonstrated typical skin changes of DM. All patients, except 2, received corticosteroids at the onset of the disease, 23 were treated with azathioprine, 7 received cyclophosphamide, 4 methotrexate, and 1 had total body irradiation. Among the patients adequately treated with azathioprine, 75% had a good response, but 5 patients did not improve. Cyclophosphamide was used subsequently in 2, with a satisfactory response in 1. Another patient had a striking response to oral methotrexate, and total body irradiation helped to improve another patient. Although high dose corticosteroids were the preferred starting medication for the treatment of PM-DM, it is important to detect those patients who do not respond adequately and/or develop side effects. In these circumstances, the prompt use of immunosuppressive agents appears justified. PMID- 2251507 TI - Proposition: methotrexate should not be the first second-line agent to be used in rheumatoid arthritis if NSAIDs fail. AB - Although methotrexate (MTX) is an effective antirheumatic drug, it cannot clearly be defined as a disease modifying antirheumatic drug (DMARD), when this term is characterized by its effect on radiographs or laboratory data. Current data, in the form of small studies or case reports, show that MTX's hepatic toxicity is not yet fully defined, that its acute pulmonary toxicity is significant, that systemic fungal infections may be associated with MTX use in rheumatoid arthritis (RA), that unexplained significant weight loss can be a problem, and that the consequence of drug interactions with MTX are not yet fully known. Thus, although clearly an effective antiinflammatory drug in RA, the place of MTX in the RA armamentarium is not fully defined. For this reason, MTX should not at present be used as the first second-line agent in RA after nonsteroidal antiinflammatory drugs (NSAIDs) fail. PMID- 2251508 TI - Resolve: methotrexate is the drug of choice after NSAIDs in rheumatoid arthritis. AB - This article, in favor of the resolution that methotrexate (MTX) is the drug of choice after nonsteroidal antiinflammatory treatment, develops the following four points. MTX is an effective treatment of rheumatoid arthritis. MTX is easy to administer and to monitor for effectiveness and safety. MTX has demonstrated a therapeutic to toxic ratio that exceeds that of other second-line antirheumatic drugs. MTX has the potential to impair disease progression. PMID- 2251509 TI - Antiphospholipid antibody syndrome: immunologic and clinical aspects. AB - Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss, and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. A positive antiphospholipid antibody test is defined by enzyme-linked immunosorbent assay (ELISA) (antiphospholipid antibody itself) or by coagulation assay (lupus anticoagulant). These are similar but not identical antibodies. The test for syphilis is less closely related to the preceding two and is less regularly associated with clinical complications. The mechanism of action of either antiphospholipid antibody or lupus anticoagulant is as yet unknown. SLE induced but not infection-induced antiphospholipid antibody has immunoglobulin G2 (IgG2) and IgG4 predominance. It recognizes all negatively charged phospholipids, but various physical characteristics of the phospholipids alter the recognition patterns. Treatment for the antiphospholipid antibody syndrome has not been clearly defined. Anticoagulation with aspirin, heparin, or warfarin is currently favored. A role for corticosteroid remains to be demonstrated. PMID- 2251511 TI - Hodgkin's disease. PMID- 2251510 TI - Nutritional status and growth in juvenile rheumatoid arthritis. AB - The specific cause of short stature in juvenile rheumatoid arthritis (JRA) is unknown. One hypothesis links altered growth to inadequate dietary intake. In this study, nutritional status was assessed in 34 children with JRA (8 with systemic JRA, 14 with polyarticular JRA, and 12 with pauciarticular JRA) and 9 healthy controls using 3-day diet records, anthropometrics, and biochemical analyses. Differences in growth were found among the three types of JRA. One third of all subjects were at or below the 10th percentile in height for age (these being predominantly among the systemic and polyarticular groups). With few exceptions, the mean dietary intake for calories and essential nutrients was found to be adequate for each of the three groups. However, more than half of those with systemic JRA reportedly consumed less than the recommended caloric intake for their age and weight. No significant correlations were found linking dietary intake to growth percentiles in any of the groups studied. Biochemical abnormalities were found among the systemic and polyarticular groups. These abnormalities included low plasma levels of vitamins A and C, proteins (albumin, prealbumin, and retinol binding protein) and zinc; and increased levels of copper and glutathione peroxidase activity. Plasma selenium and vitamin E levels were unchanged. The discrepancy between intake and certain circulating nutrient levels may reflect alterations in the requirements, absorption, or use of these nutrients in the presence of chronic inflammation. PMID- 2251512 TI - Hodgkin's disease in black populations: a review of the epidemiologic literature. PMID- 2251513 TI - The cell of origin in Hodgkin's disease. PMID- 2251514 TI - The impact of Hodgkin's disease on the immune system. AB - Patients with Hodgkin's disease, at presentation or in remission, exhibit a persistent defect in cellular immunity. Natural killer cell mediated cytotoxicity is depressed in untreated patients. Humoral immune function is transiently reduced following treatment. The cellular immune defect appears to be the result of enhanced sensitivity to suppressor monocytes and T-suppressor cells, in addition to abnormal interleukin-2 production. Patients with advanced disease have an inherent T-lymphocyte defect. Reed-Sternberg cells function as antigen presenting cells for mitogen-induced and mixed lymphocyte T-cell proliferation. PMID- 2251515 TI - The pathology of Hodgkin's disease. PMID- 2251516 TI - Staging for Hodgkin's disease. PMID- 2251517 TI - Radiation therapy in the management of Hodgkin's disease. PMID- 2251518 TI - The use of chemotherapy in the treatment of Hodgkin's disease. PMID- 2251519 TI - Hodgkin's disease in children. PMID- 2251520 TI - Hodgkin's disease: the role of bone marrow transplantation. AB - Because results with conventional salvage therapy remain disappointing, the approach of using high-dose therapy and bone marrow transplantation has gained increasing support in recent years. Several trials have now been reported using various conditioning regimens and hematopoietic rescue sources. Although it is not clear which high-dose chemotherapy is the best conditioning regimen, many of the trials contain patients who are long-term disease-free survivors using this therapeutic approach. As more experience is gained with this therapy, the patient population for which it offers the best results will be better defined. High-dose therapy and bone marrow transplantation has been shown to offer better long-term disease-free survival to patients who are transplanted after failing one or two chemotherapy regimens, have good performance status, and still have chemotherapy sensitive disease. For research to continue in this area, it is important that patients who are otherwise eligible for high-dose therapy and bone marrow transplantation participate in clinical trials to address the unanswered questions concerning high-dose therapy and bone marrow transplantation. PMID- 2251522 TI - On procrastination. PMID- 2251521 TI - Survival outcome after Hodgkin's disease: a report from the international data base on Hodgkin's disease. PMID- 2251523 TI - All I want for Christmas... PMID- 2251524 TI - The apotheosis of 'safe sex': please don't say the 'A' word here. PMID- 2251525 TI - AIDS, minority patients, and doctors: what's the risk? Who's talking? AB - We asked 39 physicians providing primary care for a mostly minority patient population to respond to a questionnaire concerning their attitudes and behavior toward AIDS risk assessment and preventive counseling and to indicate their beliefs concerning patients' knowledge and behavior. Most of the 36 physicians who responded (92%) agreed that physicians must educate their patients about AIDS. They also reported that patients who engage in risk-taking behavior may not know much about AIDS transmission and prevention. Despite these beliefs, these doctors reported that they gave advice to only 11% of their male patients and 14% of their female patients. More than one third of physicians reported feeling uncomfortable talking about patients' sexual preferences and practices. To identify patients at risk and to help prevent AIDS, methods must be found to make physicians more comfortable discussing sexual issues with their patients, especially their minority patients. PMID- 2251526 TI - Chancroid: results from an outbreak in Houston, Texas. AB - A recent (and continuing) epidemic of chancroid in Houston has included morphologic variation in the disease, including so-called dwarf, classic, giant, transient, follicular, phagedenic, and pseudogranuloma inguinale types. Most cases were clearly acquired by unprotected sexual encounters with local prostitutes. The strain of Haemophilus ducreyi responsible for this outbreak was relatively easily cultured on routine media; unexpected sensitivity of this strain to vancomycin rendered the recommended "selective" growth medium much less optimal for isolation. Therapeutic success uniformly followed the use of intramuscular ceftriaxone sodium; one case responded to oral ciprofloxacin hydrochloride. PMID- 2251527 TI - Morbidly obese patients' perceptions of social discrimination before and after surgery for obesity. AB - Morbidly obese patients' perceptions of obesity-related prejudice and discrimination were assessed before and 14 months after operation for obesity. Preoperatively, the 57 consecutive patients perceived overwhelming prejudice and discrimination at work, within the family, and in public places. After a weight loss of more than 45.5 kg (100 lb), these patients perceived little or no prejudice or discrimination. We examine factors contributing to the change in patients' perceptions and comment upon patients' perceptions of the negative attitudes held by health professionals toward obese patients. PMID- 2251528 TI - Attention deficit hyperactivity disorder: does it affect adults too? AB - A review of the literature and our experience suggest that attention deficit hyperactivity disorder does not necessarily disappear in adolescence but may persist into adult life. Detection of the disorder later in life may be made more difficult when it is masked by other diagnostic labels. Once the disorder has been identified in the adult, however, proper intervention with psychotherapy and medical management can make a significant difference in the patient's life. PMID- 2251530 TI - A resurgence of acute rheumatic fever in a mid-South children's hospital. AB - A resurgence of acute rheumatic fever (ARF) has been reported in many areas of the United States in recent years. We retrospectively reviewed the medical records of inpatients with a new diagnosis of ARF from 1982 through 1988 at a children's hospital that serves a six-state referral area in the mid-South. Thirty patients were identified, 21 of whom were seen in 1987 (13) and 1988 (8). The rate of new cases of ARF per 1000 hospital discharges (0.7) was significantly greater for 1987 and 1988 than it was (0.15) from 1982 through 1986. Patients with recently diagnosed ARF were predominantly from nonurban areas, and polyarthritis was the most common recent major manifestation. Reasons for the resurgence of ARF in the US, including the mid-South, are unclear, but our experience serves to support recently published guidelines for the diagnosis and management of streptococcal pharyngitis in light of this resurgence of ARF. PMID- 2251529 TI - Head and neck paragangliomas: a clinicopathologic study with DNA flow cytometric analysis. AB - A total of 11 head and neck paragangliomas were the subject of pathologic study, including histologic, immunohistochemical, and DNA flow cytometric analyses. We cannot absolutely predict aggressive clinical behavior using histologic parameters alone, but we can use such parameters to segregate patients into low risk and high-risk groups. Several trends were observed in the current study. Tumors with higher S-phase fractions, G2/M fractions, or aneuploid cell populations tended to behave "aggressively." The presence of sustentacular cells in the primary tumors cannot be used as an absolute indicator of tumor metastatic potential, as two metastatic paragangliomas in this study contained sustentacular cells in both the primary and metastatic lesions. DNA ploidy status cannot be used as an absolute prognostic parameter as the two metastatic tumors were composed of diploid primary and metastatic lesions. The three tumors with aneuploid cell populations showed "aggressive" histologic and clinical features, but the length of the follow-up period for these cases is too limited to draw any conclusions. Although no absolute criteria can be used at present to gauge aggressiveness, close follow-up of these patients is essential, especially if pathologic findings suggest an "aggressive" course (ie, "malignant" histology, higher S-phase fractions, G2/M fractions, aneuploid cell populations, or decreased sustentacular cell density). PMID- 2251531 TI - Physician documentation of diabetes care: use of a diabetes flow sheet and patient education clinic. AB - We assessed two interventions designed to improve the care of patients with diabetes mellitus by documenting the complications of their disease. These were a flow sheet, included with outpatient medical records, and a weekly patient education clinic, in which a nurse educator provided individualized instruction to patients with diabetes. Physician compliance with recommendations of the National Diabetes Advisory Board for diabetes care was measured before (n = 45) and after (n = 158) these interventions. The numbers of referrals to ophthalmologists increased from 22% to 46%, urinalyses increased from 58% to 77%, and lower extremity examinations increased from 36% to 61%. Nutrition education documentation increased from 51% to 69%, and diabetes education documentation increased from 31% to 61%. These results suggest that a significant improvement in physicians' documentation of care of patients with diabetes can be achieved by using a flow sheet and a diabetes patient education clinic. PMID- 2251532 TI - Femorofemoral bypass: a profile of graft failure. AB - We have reviewed our experience with 71 patients who had a femorofemoral bypass for unilateral iliac artery occlusion or stenosis. We analyzed morbidity, mortality, initial relief of symptoms, early patency, and long-term primary and secondary patency; and we attempted to identify the cause of graft failure. The overall hospital mortality after operative repair was 4%. One-year survival was 84% and 2-year survival was 81%. Early patency was 98.5% at 1 month, late patency was 91% at 1 year and 82% at 5 years. The major cause of graft failure was inadequate run-off and outflow disease progression. PMID- 2251533 TI - Deep femoral to anterior tibial bypass after failed femoropopliteal reconstructions. AB - Deep femoral to anterior tibial artery bypass is a reconstructive technique occasionally applicable when more conventional attempts at revascularization of the distal portion of the leg have failed. Three such patients, in whom the anterior tibial was the only distal patent branch of the popliteal artery, had severe symptoms of arterial insufficiency. Deep femoral to anterior tibial bypass was done using autogenous The distal portion of the deep femoral artery was exposed through an anteromedial distal thigh approach. The three patients have been followed up for a mean of 20.3 months, and each maintains graft patency and marked symptomatic improvement. PMID- 2251534 TI - Screening for slight albuminuria: a comparison of selected commercially available methods. AB - Slight albuminuria predicts clinically significant nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and early death in patients with non insulin-dependent diabetes mellitus (NIDDM). This study compares four commercially available methods for measuring low concentrations of urinary albumin. We tested random spot urine specimens from 50 nondiabetic volunteers and 100 diabetic patients. This specimen was chosen to simplify collection in an outpatient setting. Two screening methods were evaluated for their ability to detect urinary albumin in the range of 15 to 200 mg/L. Sensitivity and specificity were 100% and 54.7%, respectively, for the Ames Micro-Bumintest; and 95.5% and 91.5%, respectively, for the Sclavo Albumin Screen. The high number of false-positive results made the Micro-Bumintest unacceptable. The Albumin Screen yielded fewer false-positive results, but also produced some false-negatives. Two quantitative methods, a radioimmunoassay (RIA) and a turbidimetric assay (the SPQ Microalbumin), yielded results that agreed well with each other. PMID- 2251535 TI - Angiodysplasia: characterization, diagnosis, and advances in treatment. AB - Gastrointestinal bleeding accounts for 2% of all adult hospital admissions each year. Angiodysplasia is one of the most frequently reported causes of lower gastrointestinal bleeding. In 80% of patients with bleeding angiodysplasia, the bleeding will stop spontaneously, but will often recur. Although angiography may detect bleeding in 86% of actively bleeding patients, the bleeding rate must be at least 0.5 mL/min. The treatment of choice for control of bleeding has been resection of the suspected segment of bowel, but this procedure is associated with a 10% rebleeding rate and 7% to 8% mortality. Superselective catheterization with infusion of vasoconstrictors has been used to control bleeding, but effects are short-lived. Superselective embolization occludes an offending vessel, but is difficult to perform accurately and is associated with risk of infarction. Laser photocoagulation controls bleeding in 84% of patients, with a 6% complication rate. This method of controlling bleeding offers distinct advantages, especially for the hemodynamically unstable patient. Except for cases in which surgical resection is indicated, Nd:YAG laser photocoagulation is the safest, least invasive, and probably most effective means of treating angiodysplasia. PMID- 2251536 TI - Folic acid, 1991: an update, with new recommended daily allowances. PMID- 2251537 TI - Apical hypertrophic cardiomyopathy in a non-Oriental man. AB - Japanese investigators first described apical HCM in 2.9% of patients who had diagnostic left ventricular catheterization for suspected ischemic heart disease or cardiomyopathy. This entity was initially thought to be limited to individuals of Asian origin and has been uncommonly described in patients of Western origin. Patients of Western origin differ in several ways from those in the original description of Yamaguchi et al, but they both share the same classic criterion of hypertrophy of the left ventricular apex. The major differences probably relate to the anatomic variation in the distribution of the left ventricular hypertrophy as described by Maron et al. It is not known whether racial, genetic, or environmental factors account for the variation of disease expression in Asian and Western patients. Our case illustrates that this diagnosis should be considered in patients who have chest pain (anginal or atypical) and markedly abnormal findings on electrocardiograms in the absence of hypertension or significant coronary artery disease. PMID- 2251538 TI - Sternoclavicular septic arthritis due to haemophilus influenzae. AB - We have reported a case of septic sternoclavicular arthritis illustrating a rare complication of infection with a relatively common pathogen, Haemophilus influenze. Early identification of the infecting organism and appropriate antibiotic therapy are essential to prevent further morbidity from the complications of this unusual pyoarthritis. PMID- 2251539 TI - Pheochromocytoma and acute myocardial infarction. AB - When a pheochromocytoma is manifested as an acute myocardial illness, diagnosis may be difficult to make. If the tumor is suspected early enough, a workup can be done while the complications of the myocardial illness are being controlled (as in our case). The tumor can then be expeditiously removed before any further problems develop. The case presented here underscores the importance of maintaining a high index of suspicion for a pheochromocytoma in any patient who has an unexpected myocardial event. PMID- 2251540 TI - Complete jejunoileal necrosis due to torsion of the superior mesenteric artery. AB - We have reported a case of small-bowel volvulus in which complete jejunoileal necrosis resulted from torsion of the superior mesenteric artery. This case was unusual not only because of the extent of necrosis but also because primary small bowel volvulus is rare in adults. Despite nearly total small-bowel resection, the patient continues to do well 6 months postoperatively. PMID- 2251541 TI - Ulcerative lesions and herpes simplex virus type 2 in a patient with Evan's syndrome. AB - We have described a case of herpes genitalis in a patient with Evans's syndrome who had violaceous macules leading to deep ulcerations. This case serves as a reminder that HSV infection may be atypical and have an unusual course in immunocompromised patients. With the availability of specific therapy for this infection, it is important to consider HSV in the differential diagnosis of all ulcerative skin lesions. PMID- 2251542 TI - Cardiovascular anomalies associated with prenatal exposure to theophylline. AB - Theophylline has been shown to be a potent cardiovascular teratogen in animals, but there has been no evidence linking theophylline with congenital anomalies in infants. The cardiovascular anomalies in our three patients were aortic anomalies, double-outlet right ventricle, transposition of the great arteries, total anomalous pulmonary venous connection, and hypoplasia of the left ventricle. Some of these rare defects were also induced frequently in animal experiments with theophylline, which suggests that this drug can be a cardiovascular teratogen in a susceptible human fetus. PMID- 2251543 TI - Treatment of postphlebitic lipodermatosclerosis. PMID- 2251545 TI - Jejunal adenocarcinoma manifested as an adnexal mass. PMID- 2251544 TI - A Creutzfeldt-Jakob-like syndrome due to polypharmacy. PMID- 2251546 TI - Umbilical stump keloid. PMID- 2251547 TI - [Apparatus for fixation of fractures of the forearm bones with preservation of the function of the radioulnar articulation]. PMID- 2251548 TI - [A case of osteomyelofibrosis with jaundice]. PMID- 2251549 TI - [A complicated course of idiopathic thrombocytopenic purpura]. PMID- 2251551 TI - [Multiple sclerosis associated with myasthenia gravis]. PMID- 2251550 TI - [Immunomodulating properties of leukinferon]. AB - Tolerance and immunomodulating properties of leukinferon for injections were studied in 13 healthy volunteers. The drug was administered by inhalation and intramuscularly in a single dose of 10,000 MU twice daily for 3 days. Intramuscular injections of the drug were accompanied by a number of side effects: pyrogenicity, weakness, headache, that ceased 8-12 hrs after the drug was discontinued. Despite these side effects, the drug was satisfactorily tolerated. Neither viscera nor systemic disorders nor allergic reactions were detected. T-lymphocytes proved to be the most sensitive to the drug. Leukinferon was found to activate the interferon system. The effect was the most marked in respect of IRL-gamma. PMID- 2251552 TI - [Effect of nadolol on central and regional hemodynamics in arterial hypertension]. PMID- 2251553 TI - [Effect of early physical activation on the course of myocardial infarction]. PMID- 2251554 TI - [Combined roentgenological examinations in neoplasms of the major salivary glands]. PMID- 2251555 TI - [Metastasis as a prognostic factor in cancer of the thoracic segment of the esophagus]. AB - Prognostic value of metastases is analyzed on the basis of the results of surgical and combined treatment of 631 cases with carcinoma of the thoracic portion of the esophagus. The metastasizing factor was found to correlate with the depth of the tumor invasion and size. The presence of metastases reduces the possibility of radical operations and lowers the index of 5-year survival. PMID- 2251556 TI - [Breast cancer and the background processes]. AB - A morphologic study of the background changes in mammary tissue was carried out, based on systematization of elementary, nosologically and morphologically well determined parenchymatous structures with the use of analysis of correlations. Regularities in the relationships between parenchymatous changes were revealed, depending on the site and severity of epithelial dysplasia. Statistical analysis has proved that grave epithelial dysplasia is a marker of high risk of preinvasive and invasive carcinoma. Histologic structure of both invasive and preinvasive carcinoma is not always determined by the site of grave epithelial dysplasia in certain type structures. Regularities in relationships and combinations of parenchymatous structures associated with severe epithelial dysplasia are diagnostically valuable for the detection of preinvasive and invasive carcinoma irrespective of its histologic form. PMID- 2251557 TI - [Biomechanism of magneto-laser therapy]. PMID- 2251558 TI - [AIDS and mycoses]. PMID- 2251559 TI - [Medico-legal evaluation of unfavorable outcomes in medical practice]. PMID- 2251560 TI - [Plasmapheresis as an optimal method to improve the outcome of surgical diseases]. PMID- 2251561 TI - [Cardiac glycosides in the complex treatment of chronic cor pulmonale]. PMID- 2251562 TI - [Automated working places of physicians-gastroenterologists]. PMID- 2251563 TI - [Principles and organization of the activities of teachers in the internal medicine department]. PMID- 2251564 TI - [Pulsatile Doppler echocardiography in the evaluation of the functional state of the myocardium in ischemic heart disease]. PMID- 2251565 TI - [Bicycle ergometry in the early post-infarction period]. PMID- 2251566 TI - [Rare developmental anomalies of the right cardiac ventricle]. PMID- 2251567 TI - [External respiratory function in the surgical treatment of bullous pulmonary emphysema]. PMID- 2251568 TI - [Plasmapheresis and plasma sorption after surgical treatment of acute intestinal obstruction]. PMID- 2251569 TI - [Physio-hemotherapy in the complex detoxification of the body in acute exogenic poisoning]. PMID- 2251570 TI - [Comparative evaluation of the effectiveness of alternating low-frequency magnetic field in chronic cholecystitis]. PMID- 2251571 TI - [Photomodification of autologous blood in the complex treatment and prevention of peritonitis]. PMID- 2251572 TI - [Treatment of acute hepatitis B with deoxyribonuclease]. PMID- 2251573 TI - [Therapeutic and diagnostic endoscopic procedures in mechanical jaundice]. PMID- 2251574 TI - [Radioisotope diagnosis of the changes in the hepatobiliary tract in children]. PMID- 2251575 TI - [Ultrasonography and computerized tomography in diseases of the organs of the abdominal cavity and retroperitoneal space]. PMID- 2251576 TI - [Ambulatory endoscopic operations on the gastrointestinal tract]. PMID- 2251578 TI - [Professional profiles of surgeons in the surgical specialties]. PMID- 2251577 TI - [Elimination of cicatricial deformities and defects of the skin by the method of soft tissue expansion]. PMID- 2251579 TI - [Surgery in congenital sternal cleft with a covered ectopia cordis using Sabiston's sternal plasty method]. PMID- 2251580 TI - [Surgical treatment of congenital vascular anomalies causing tracheoesophageal compression]. AB - Forty four children underwent surgery for congenital vascular anomalies causing tracheal compression in Kardiocentrum--Motol during last ten years. Double aortic arch was encountered 18 times, tracheal compression by the innominate artery in 12 instances, right aortic arch with left ligamentum arteriosum and possibly aberrant left subclavian artery 7 times, pulmonary artery sling in 5, finally aberrant right subclavian artery twice. The age of the children was 2 weeks to 11 years (median 6 months). Stridor was present in 38 infants under 3 months, 17 children with severe dyspnoea had artificial ventilation or were resuscitated or hospitalized at the intensive care department. In four an associated cardiac defects was present. The diagnosis was made by oesophagography, echography, laryngotracheoscopy, in the majority of children it was confirmed by angiography of the sometime with tracheobronchography. The operation was performed in 41 children from left-sided thoracotomy, the vascular ring was released by resection or retraction of the compromising vessel and connective tissue from the trachea. Serious stenosis of the distal trachea in one patient found before operation persists one year after operation, the patient breathes through an individual tracheostomic cannula. Four children could not be extubated for prolonged periods after operation, they were re-operated, the annulus was released. Three patients died, one from bronchopneumonia during the postoperative period, the second one from hypoxic brain damage and the third one after operation of a complex heart disease. In 40 children satisfactory long-term results were achieved, the operation resolved respiratory complaints. The prerequisite of satisfactory results in an accurate diagnosis, early indication of the operation and a perfect surgical operation and good postoperative care. PMID- 2251581 TI - [Miniaturized extracorporeal circulation for infants]. AB - By using the smallest commercially available oxygenator and our own modification of an apparatus for extracorporeal circulation we achieved minimal filling. By placing the apparatus close to the operating table the set can be miniaturized and the length of the tubes can be maximally reduced, while a satisfactory overview is ensured. The authors compared a group of 10 children operated by using this miniature apparatus with a control group of 20 children where the standard set up was used. The filling of the apparatus incl. added solutions was significantly smaller in the group with the mini-apparatus--on average 420 ml, as compared with the control group (671 ml). Despite the substantially larger amount of transfused blood in the control group with the greater volume (500 ml/patient), the resulting packed cell volume was the same in both groups. The other common postoperative parameters did not differ significantly in the two groups. The minimal filling of the apparatus for extracorporeal circulation in the described set up makes possible in the majority of children and infants with an elevated packed cell volume perfusion without the use of donor blood which is consistent with contemporary trends. PMID- 2251582 TI - [Possible use of the autotransfusion technic in pediatric heart surgery]. AB - Consequential miniaturization of the apparatus for extracorporeal circulation and its simple connection, by introduction of haemodilution into perfusion technique along with careful surgical technique and the introduction of the principle of autotransfusion made it possible to reduce the consumption of donor blood in our department during the last six years to 25%. Autotransfusion proved to be in children weighing more than 15 kg a safe method. In the first half of 1989 we made 194 operations of the open heart. 167 patients (i.e. 86%) of this number did not require preserved blood in the primary filling of the apparatus for extracorporeal circulation. In a group of 100 patients weighing more than 15 kg in 65% the method of autotransfusion was applied; 55% of the patients did not need donor blood in the course of hospitalization. PMID- 2251583 TI - [Morphological and angiocardiographic study of atrioventricular septal defects]. AB - A group of post-mortem specimens of 82 hearts with a defect of the atrioventricular septum (atrioventricular canal) was retrospectively examined with special attention to the morphology of the defect in relation to the left atrioventricular anastomosis. In 42 preparations the finding was compared with previous angiocardiography and post-mortally with X-ray pictures of the specimens. Correlation of the findings revealed malformation of the left atrioventricular orifice as part of a complex malformation affecting the valvular apparatus in conjunction with the atrioventricular septal defect. In the very variable anatomical morphology a major part is played by the superior cusp of the left atrioventricular anastomosis. The relationship of the superior cusp to the outflow tract of the left ventricle and to the atrioventricular septal defect has an impact on the variability of the angiocardiographic picture, and last but not least, also on the results of surgical treatment. The anteroposterior, left oblique and hepatoclavicular projections are optimal for visualization of the anomaly. PMID- 2251584 TI - [Prophylactic administration of Klion in acute appendicitis]. AB - The authors present their experience with the prophylactic administration of metronidazole of Richter Co. Hungary (trade name Klion) in children with phlegmonous appendicitis. The preparation was administered in three doses to 51 children. The bacteriological results were evaluated in 42 children. The results of Klion administration in phlegmonous appendicitis were excellent. In the investigated group there were no wound inflammatory nor intraabdominal complications. For comparison the authors mention a group of 1008 children with phlegmonous appendicitis without prophylactic provisions where the number of inflammatory wound complications was 3.62%. Klion has minimal side-effects, was well tolerated and proved excellent for prophylactic administration. PMID- 2251585 TI - [Infectious diseases in children complicated by appendicitis]. AB - The authors draw attention to the pitfalls in the diagnosis and treatment of children who develop abdominal pain in the course of an infection. Based on many years experience with the nursing and treatment of children at the Isolation Clinics of the Faculty Hospital and Policlinic Na Bulovce, rPague the authors evaluated a group of children (1982-1987) treated most frequently on account of parotitis, varicella, diarrhoeal disease and meningitis who developed concurrently symptoms of true or false acute abdomen. The authors analyze the most frequent diagnostic and therapeutic errors which cause deterioration of the course and prognosis of surgical acute abdomen in children whose health status is adversely influenced by the infectious disease. PMID- 2251587 TI - [Thoracic injuries in children]. AB - During the period between 1967 and 1987 at the Paediatric Surgical Clinic in Brno 87 multiple injuries with a dominant affection of the chest were treated. Two patients from the group died. The mortality increases considerably in groups with combined injuries of the chest and other parts of the body. The authors give indications for surgical treatment of chest injuries and their own experience with the treatment of associated injuries of the chest in children. PMID- 2251586 TI - [Ileus after appendicitis in children]. AB - A relatively frequent and alarming complication of appendicitis in children is ileus. The authors submit an analysis of 41 cases of ileus with a time interval of 3 days to 8 years after appendectomy. In eight patients conservative treatment was successful, and 33 children were operated with the finding of intraabdominal adhesions (23 times), bands (3 times), abscesses and adhesions (7 times). Two children were re-operated on account a relapsing ileus. None of the children died. Prophylaxis of ileus after appendectomy is ineffective and uncertain, therefore the authors emphasize early diagnosis and early operation of the appendicitis but warn against inadequately considered appendectomy. PMID- 2251588 TI - [Traumatic obstruction of the duodenum]. AB - The authors describe a rare observation of traumatic duodenal obstruction by an intramural haematoma with concurrent extensive retroperitoneal haemorrhage and a minor haemoperitoneum in a six-year-old girl who fell and hurt her abdomen on a flat stone. The first symptoms--abdominal pain and vomiting--developed 24 hours after the injury. She was referred to hospital and admitted only three days after the injury with the clinical picture of an inflammatory acute abdomen with peritoneal irritation, concurrent with a respiratory infection persisting for four days. Based on the authors' own observation and data in the literature the diagnostic possibilities are analyzed as well as pitfalls and the optimal therapeutic procedure in this rare type of injury. PMID- 2251589 TI - [Posttraumatic biliary pseudocyst of the liver in a child]. AB - The authors describe a rare complication of a severe liver injury--the development of a post-traumatic biliary pseudocyst--in a 5-year-old child with a multiple injury. The pseudocyst was detected by ultrasound and computed tomography when searching for the cause of the persisting septic condition following prolonged resuscitation during the postoperative period. Percutaneous puncture drainage by means of a pigtail made under sonographic control, although because of limited experience it was repeated, led to recovery of the child. Thus it proved possible to resolve a post-traumatic infected biliary hepatic pseudocyst without a major invasion into the child's organism which was severely affected by the multiple injury as well as septic condition. PMID- 2251590 TI - [Unusual burns in older boys]. AB - The authors give an account a less frequent mechanism of burns in older boys during the domestic manufacture of smoke-boxes from a mixture of sodium dithionite (decolourizer) and urea peroxyhydrate (solid hydrogen peroxide). The chemical reaction explains the development of exogenous heat and the depth of burns. The authors analyze their own material of 16 patients and emphasize early necrectomy and prevention. PMID- 2251591 TI - [Our attitude to the so-called extended surgical procedures for colorectal carcinoma]. AB - The authors present their experience with 29 extended operations performed on account of tumours of the sigmoid, rectosigmoid and rectum. These operations accounted for 13.4% of all operations on account of operable tumours of the colon and rectum in 1984-1988. In addition to the basic operation one organ was removed 11 times, two organs twice, three organs four times and four organs were removed en bloc twice. Complications occurred in 61% of the patients, the mortality rate was 6.9%. The authors submit an account of recent views published in the literature on the given subject with emphasis on en bloc resection, and conclude that when certain principles are respected, these extended operations are justified. PMID- 2251592 TI - [Transplantation of embryonal nerve tissue into the brain of donors under experimental and clinical conditions]. AB - The authors, stimulated by the results of transplantations of embryonic nervous tissue under experimental conditions and by findings on the biochemical background of some manifestations of mental diseases, dared to use for the first time transplantation of portions of human embryonic brain in the treatment of schizophrenia. Before the experiment they evaluated the bilateral xeno as well as autotransplantations in ten cats. Under clinical conditions they used transplantation of embryonic nervous tissue in two patients with the acute and chronic form of schizophrenia. The operation was performed, using Mundinger's stereotactic apparatus controlled by a computer. The tissue from the central portion of the embryonic brain from the 5th and 7th week of gestation with a high serotonin content was deposited bilaterally in the septal area in the recipient's brain. They recorded improvement in particular in a case of acute schizophrenia. By monitoring the foci of transplanted tissue by computed tomography and magnetic resonance, they provided evidence that embryonic nervous tissue is incorporated in the recipient's brain without reverting into malignant growth and that it is not rejected by the immune system of the recipient. PMID- 2251593 TI - [Bronchopleural fistula as a complication of pulmonary resection]. AB - During a 15-year period, when in the department for thoracic surgery in the Research Institute for Tuberculosis and Respiratory Diseases 1612 resections of the lungs were performed, the authors recorded 18 patients with bronchopleural fistulae. After pneumonectomies and lobectomies the incidence of this complication was recorded in 1.4%. The majority of fistulae was observed after resection on the lungs on account of bronchogenic carcinoma, in two patients after resection on account of a pulmonary aspergilloma. After resection on account of TB and bronchiectas is the authors did not observe bronchopleural fistulae. Treatment of the fistula was in two thirds of the patients of the investigated group conservative with a 33% lethality. In six patients on account of the fistula rethoracotomy was performed with a lethality of 66.6%. The total lethality during treatment of bronchopleural fistulae was 44.4%. The purpose of the present work is to draw attention to the serious character of this post resection complication and to its possible prevention by preoperative preparation and surgical technique. PMID- 2251594 TI - [Postoperative hypoxemia in aged surgical patients]. AB - The authors analyze postoperative hypoxaemia in a group of 48 patients aged 60 years or more after operation in the upper half of the abdomen. Hypoxaemia with values below 8 kPa in the arterial blood stream which are classified as a respiratory insufficiency were recorded in this group in 52%. In the mechanism of development they draw attention to changes which lead to the formation of atelectases and an impaired relationship of ventilation and perfusion. They draw attention to risk factors and polymorbidity in this age group. In their opinion a suitable indicator of impaired pulmonary function before operation are gas levels in arterial blood compared to normal ones. They emphasize a comprehensive approach in prevention and treatment. PMID- 2251595 TI - [Surgery of the spleen in relation to portal hypertension]. AB - Unfounded splenectomy in portal hypertension exposes the patients to several risks. This is apparent from presented case-histories as well as reviews and the authors' experience. The authors emphasize general principles of the approach to surgery of the spleen in portal hypertension. PMID- 2251596 TI - [Scintigraphic determination of the function of an autotransplanted spleen]. AB - In an 8-year-old boy after abdominal injury scintigraphically, using radiocolloid labelled 99mTc, suspicion of a ruptured spleen was confirmed. Therefore splenectomy was performed and an autotransplantation of a portion of the spleen into the great omentum. After three months during scintigraphy performed with autologous thermally damaged and indium 113mIn labelled erythrocytes a small functional autotransplant of the spleen on the left side of the navel was revealed. Twelve months after operation scintigraphy confirmed its vitality and even an increase in size. Scintigraphy by means of damaged and labelled erythrocytes is the only visualization method to reveal vitality and functioning of autotransplants of the spleen. PMID- 2251597 TI - [Indications for peroperative cholangiography in cholecystectomy]. AB - In a group of 466 cholecystectomies with peroperative cholangiography the authors revealed sensitivity of the examination for cholangiolithiasis (255 before operation) in 95.3%, for diagnosis of all benign diseases of the bile ducts (288 operations) in 95.8%. They established six indication criterias for peroperative cholangiography during cholecystectomy: 1. jaundice or elevated serum bilirubin before operation, 2. pancreatitis or elevated amylase values in blood or urine before operation, 3. elevated alkaline phosphatase (ALP) or gamma-glutamyl transpeptidase (GMT) serum values before operation, 4. small (under 3 mm) or multiple (more than 10) gallstones, 5. a choledochus wider than 10 mm, 6 a cystic duct wider than 3 mm. As indication suffices positivity of one of the criteria. By introducing these indications it was possible to reduce peroperative cholangiography during cholecystectomies by cca 40% with a 0.1% risk of diagnostic errors in the diagnosis of benign diseases of the bile ducts. PMID- 2251598 TI - [Endometriosis as a cause of obstruction of the small intestine]. AB - The authors describe a rare case of obstruction of the small intestine, caused by extragenital endometriosis in the stage of proliferation with progressing endometriosis. Resection of the affected portion of the ileum with decompression of the dilated loops and end-to-end anastomosis led to rapid restoration of the passage and to the patient's recovery. PMID- 2251599 TI - [Carcinoma of the large intestine and cholecystectomy]. AB - The authors draw attention to the high incidence of carcinoma of the large intestine in conjunction with cholecystectomy. The increased incidence of this disease was observed in patients after cholecystectomy (17.69%). The authors processed data from a group of 260 patients with colorectal carcinoma during the ten-year period from 1979 to 1988, in 46 with cholelithiasis during previous period cholecystectomy was performed, i.e. in 17.69%. It is assumed that the stimulating effect in carcinogenesis of the large intestine are changes in the bile acid metabolism occurring after cholecystectomy. Hitherto valid indications for cholecystectomy do not change, however, but make us consider these relationships in clinical practice and call for further analyses. PMID- 2251601 TI - [Czech surgeons--authors]. PMID- 2251600 TI - [A multipurpose vacuum mattress in health care]. AB - The authors draw attention to vacuum mattresses which are a modern appliance for the immobilization of casualties and patients. They present their initial experience with the use of these mattresses during examinations on a computed tomograph, during all-body stereotaxis and minor surgical operations. The material from which the mattress is made allows X-rays to penetrate, therefore it can be used also for immobilization of restless patients and children during X ray examinations. It is, however, possible to manufacture also various types of vacuum splints for fixation of the extremities after injuries. PMID- 2251602 TI - Effects of alpha-interferon on iron-related measurements in human subjects. AB - Subcutaneous administration of alpha-interferon to normal volunteers caused hypoferraemia and hyperferritinaemia. There was, however, no concomitant rise in other components of the acute-phase response, including the serum C-reactive protein value, the granulocyte count and the plasma lactoferrin concentration. In fact, the latter two dropped significantly. The hypoferraemic response could be prolonged when a second dose was given 48 hours after the initial one. This hypoferraemic response may play a role similar to that induced by interleukin-1, which limits the proliferation of invading micro-organisms or neoplastic cells. The present findings may therefore have relevance to the clinical mechanism of action of the interferons. PMID- 2251603 TI - Serum keratan sulphate levels during prolonged rest. AB - Serum levels of keratan sulphate (KS) were measured by an enzyme-linked immunosorbent-inhibition assay on admission to hospital in 26 previously healthy young patients who had sustained fractures of the pelvis without involvement of the hips. The serum KS level was found to decrease during the period in hospital (5-6 weeks), but rose after return to ambulatory life (6-12 months). The results suggest that serum KS levels are related to rest. PMID- 2251604 TI - Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease? AB - The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17 54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251605 TI - Evaluation of the post-exercise time-course behaviour of ST-segment and T-wave changes in the elimination of the false-positive stress ECG. AB - Routine stress ECG has been criticised for yielding too many so-called false positive results because ST-segment and T-wave (ST/T) changes that develop during and after exercise are prevalent. Recent studies in our institutions indicate that the time-course behaviour patterns of ST/T configurational abnormalities after exercise reflecting myocardial ischaemia are different from those that do not. The epicardial coronary arteries of 111 patients, who had positive stress tests for ischaemia based on ST/T configurational changes alone but were considered non-ischaemic when the ST/T time-course behaviour was analysed, were assessed. Of these patients, 102 had normal coronary arteries, 7 had insignificant stenoses and only 2 had significant coronary artery diseases. ST/T abnormalities on stress testing with a non-ischaemic time-course pattern should be regarded in the same category as ST segments that remain normal as far as the detection of myocardial ischaemia due to epicardial coronary artery disease is concerned. This policy has resulted in an improved predictive value of exercise testing and has considerably decreased the number of patients subjected to coronary arteriography in our institutions. The assessment of the post-exercise stress ECG remains the most practical and cost-effective method for detecting ischaemic heart disease. PMID- 2251606 TI - The role of the aortic aneurysm diameter aortic diameter ratio in predicting the risk of rupture. AB - This study was performed to examine the ratio between the size of an infrarenal aortic aneurysm and the normal aorta proximal to it, in the hope of identifying a high-risk group of patients. All patients underwent a computed tomography scan of the abdomen, at which time the diameters of the largest aneurysm and of the normal proximal aorta were measured. The ratio was calculated by dividing the diameter of the normal aorta (in centimetres) into the diameter of the aneurysm. One hundred and thirty patients were assessed. One hundred asymptomatic patients had a mean ratio of 2.0. The 30 symptomatic patients were subdivided into 2 groups; 17 were symptomatic but had no evidence of rupture (mean ratio 2.7), and the remaining 13 had a contained rupture (mean ratio 3.4). There was a significant difference between the asymptomatic patients and the two symptomatic groups (P less than 0.001). The results suggest that the aneurysm/aorta ratio may be helpful in identifying the high-risk aneurysm. Patients with a ratio of 2.7 or greater are likely to become symptomatic, whereas those with a ratio of 3.4 or greater are at risk of rupture. PMID- 2251607 TI - Dynamic skinfold thickness measurement in infants fed breast-milk, low- or high sodium formula. AB - A stratified sample of normal infants born at term at Johannesburg Hospital, who attended the hospital for a routine 6-week follow-up visit, were selected to include 43 infants who were exclusively breast-fed, 42 fed a low-sodium formula and 39 fed a high-sodium formula (greater than 10 mmol sodium/l). Dynamic skinfold thickness measurements (DSTM), designed to assess the amount of interstitial fluid, were performed on each infant by the application of a skinfold caliper for a 3-second sampling period at two sites. The curves generated by these applications were recorded and analysed by microcomputer. There were no differences between any of the feeding groups for DSTM measurements of blood pressure suggesting that the range of sodium ingested by these groups of infants had no significant effects on extracellular water content. However, using multiple linear regression, both DSTM and blood pressure were best predicted by body weight and not by age or any other anthropometric measurement. Thus the normal postnatal decrease in extracellular fluid volume and increase in blood pressure appears to be most closely related to an increase in body weight. PMID- 2251608 TI - Respiratory health status of children in the eastern Transvaal highveld. AB - A study was undertaken to determine if there were detectable effects on the respiratory health status of children resident in the eastern Transvaal highveld as a consequence of their exposure to community air pollution, comparing them with children in areas ostensibly less polluted. A prevalence study was conducted in white schoolchildren from 11 schools in the eastern Transvaal highveld (1,031 children) and from 11 schools in non-polluted towns in the Transvaal (978 children). A questionnaire was completed by each child's mother, and height and weight were measured and spirometry recorded on a vitalograph. Cough, wheeze, asthma and chest illnesses were more frequently reported from polluted areas compared with non-polluted areas, taking into account parental smoking and home cooking fuel (odds ratios 1.34, 1.20, 1.15 and 1.88, respectively). After correcting for age, children in the polluted area were 0.83 cm shorter (P = 0.035). However, there were no significant differences in forced vital capacity and forced expiratory volume in 1 second after standardising for height, age, parental smoking and home cooking fuel. We conclude that, in children, exposure to pollution in the eastern Transvaal highveld may cause respiratory symptoms and chest illness and may affect height but does not measurably affect lung function, as assessed by spirometry. PMID- 2251609 TI - Surgical correction of ventricular septal defects in black and white children--an 11-year study. AB - The clinical and ECG features, anatomical subtypes and outcome in 309 children (169 black; 140 white; 58% female) who underwent surgical closure of ventricular septal defects (VSDs) are presented. Clinical presentation was more severe in the black children; with recurrent pulmonary infections in 65% blacks compared with 34% whites. Congestive cardiac failure was noted in 60% blacks and in 37% whites. At cardiac catheterisation a left to right shunt greater than 2.5/1 was found in 45.5% of the black and in 39.3% of the white children. Severe pulmonary hypertension (greater than 80% of systemic systolic pressure) was evenly distributed in both groups. Of the 140 white children, 74.3% underwent surgery under the age of 2 years compared with 68.6% of the 169 blacks. A perimembranous VSD was found in 65% of patients in each group. Infundibular (muscular outlet) defects were observed in 28.6% of white and 30.8% of black children. Left axis deviation (LAD) on ECG was found in 11.9% of white and 9.2% of black patients; and 93% of the total of 27 cases had a perimembranous defect. Early mortality was 3.6% in white and 7.1% among the black children. Of the 17 fatal cases in the total group, 16 had severe pulmonary hypertension. It is concluded that: (i) operative results compared favourably with those reported elsewhere; (ii) the anatomical subtypes occurred with equal frequency in both ethnic groups; and (iii) this was also the case for LAD on ECG, which was most commonly associated with a perimembranous VSD. PMID- 2251610 TI - Barrett's oesophagus--radiological features in 100 cases. AB - The columnar-lined or Barrett's oesophagus is an acquired condition resulting from long-continued gastro-oesophageal reflux. In the last 20 years 149 patients with Barrett's oesophagus have been studied in the clinics of the Johannesburg Teaching Hospitals. Important radiological predictors of Barrett's oesophagus, as defined from a series of 100 cases, are the presence of a stricture well above the gastro-oesophageal junction (41 cases), a long stricture (13 cases) and ulceration in the body of the oesophagus (16 cases). An early stricture may be so subtle that it is missed or disregarded, and is the usual site of the squamocolumnar junction. Significant strictures may be seen even in the absence of a hiatus hernia. When associated with a hiatus hernia the strictures are usually concentric and are longer than the usual reflux strictures. The varying length of these strictures suggests an upward progression of the disease process, which begins at the gastro-oesophageal junction. This feature, seen in 6 of our patients, has not previously been stressed as a predictor for Barrett's oesophagus. Radiological reflux, although in itself a poor predictor, lends support to the diagnosis of Barrett's oesophagus if one or more of the other predictors is present. A less important predictor is a reticular mucosal pattern seen on double-contrast radiography. PMID- 2251611 TI - Isolated traumatic posterior dislocation of the radial head. AB - Only 4 cases of isolated posterior dislocation of the radial head in adults have been reported in the English-language literature. We describe 2 cases with a clear mechanism of injury and present a concise review of the literature. PMID- 2251612 TI - Pure word deafness. AB - Two cases of pure word deafness, both with bilateral temporal lobe lesions due to cerebrovascular disease, are presented. This rare disorder is briefly discussed. PMID- 2251613 TI - The use of nasogastric intubation in the radiological diagnosis of oesophageal atresias. AB - Correctly performed oesophageal intubation determines the presence of atresia. The physical properties of the nasogastric tube used determines the place of radiology in this diagnosis. The appearance of a curled tube (hoop sign) in the proximal oesophagus in the newborn is diagnostic of atresia, as it clearly delineates the oesophageal pouch. The performance of a contrast study to establish this diagnosis is never indicated, since it is impossible to eliminate aspiration completely. PMID- 2251614 TI - Angiotensin-converting enzyme inhibitors in pregnancy may result in neonatal renal failure. AB - Oligohydramnios and neonatal renal failure is reported in a premature infant whose mother had used enalapril in weeks 32-35 of her pregnancy. The infant recovered adequate renal function after peritoneal dialysis. Review of the literature supports our view that angiotensin-converting enzyme inhibitors should not be used in pregnancy; if they are, both mother and fetus should be monitored with extreme care. PMID- 2251615 TI - Natural childbirth--the Johannesburg Hospital experience, 1983-1989. AB - The Johannesburg Hospital Active Birth Unit (ABU), the only one of its kind in southern Africa to date, has provided an alternative to conventional labour practices since 1983. In a retrospective study of the results achieved in this unit the intrapartum records of 492 patients admitted to the ABU between 1 March 1983 and 30 June 1989 were analysed. During the 6.3-year study period 364 patients (74%) successfully laboured and delivered within the unit. These figures included 50 underwater deliveries. One hundred and twenty-eight patients required intrapartum transfer to the conventional labour ward and of these 44 achieved spontaneous vaginal delivery. Thirty-four patients (7%) 'self-selecting' for natural childbirth ultimately required caesarean section delivery. Primiparous patients were more likely than their multiparous counterparts to require intrapartum transfer to the labour ward (38% v. 13%). Birth outcome results achieved in the Johannesburg Hospital ABU compare favourably with those for 6 other ABUs reported in the literature. PMID- 2251616 TI - Adjunctive therapy with bromocriptine in Parkinson's disease. AB - Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient. PMID- 2251617 TI - Neonatal allo-immune thrombocytopenia. A case report and review of obstetric management. AB - The prime object in the obstetric management of mothers who have previously delivered an infant with neonatal alloimmune thrombocytopenia is to prevent the occurrence of intracranial haemorrhage, which may occur in subsequent pregnancies in 15-20% of infants with this disease. Elective caesarean section at 38 weeks' gestation may obviate the problem, since it prevents trauma during vaginal delivery but it will not eliminate neurological sequelae in those infants who have already suffered antenatal intracranial bleeding, an entity now well described in these fetuses. A review is presented in which all possible antenatal and post-natal modalities of treatment in the management of these cases are highlighted. PMID- 2251618 TI - The effect of magnesium sulphate infusion on circulating catecholamine levels in severe gestational proteinuric hypertension. A report of 8 cases. AB - The effect of magnesium sulphate (MgSO4) infusion on blood pressure and circulating venous catecholamine levels in 8 patients with severe gestational proteinuric hypertension is described. A significant fall in blood pressure was noted after MgSO4 infusion; the maximal fall in diastolic blood pressure correlated with the greatest rise in serum magnesium levels (P less than 0.04). No significant change was observed in mean venous plasma adrenaline or noradrenaline levels after MgSO4 infusion, although the mean dopamine concentration declined significantly. It is concluded that the decrease in systemic vascular resistance after MgSO4 infusion in gestational proteinuric hypertension is mediated predominantly by mechanisms other than a change in circulating catecholamine levels. PMID- 2251619 TI - Fanconi's anaemia in pregnancy. A case report. AB - Fanconi's anaemia associated with congenital anomalies is a rare aplastic anaemia occurring in childhood. No case of pregnancy occurring in the presence of this condition has previously been reported. The outcome of pregnancy in a patient with Fanconi's anaemia is described and guidelines for management of the disease in pregnancy suggested. PMID- 2251620 TI - Fulminant adult respiratory distress syndrome after suction lipectomy. A case report. AB - The adult respiratory distress syndrome developing within 24 hours in a patient who underwent suction lipectomy for body contouring under general anaesthesia is reported. During surgery, in which a total of 1.3 l of suction matter was removed, the patient became haemodynamically unstable and mildly hyperthermic. Subsequently, clinical signs and symptoms of the fat embolism syndrome developed. Aggressive haemodynamic and respiratory support over an 8-day period resulted in patient survival. Malignant hyperthermia was excluded as cause for the clinical presentation on muscle biopsy and in vitro caffeine contracture studies. Although usually complication-free, suction lipectomy may be associated with life threatening incidents. Even suction volumes as low as 1.3 l have potential hazards, therefore the procedure merits regular postoperative observation and re assessment. PMID- 2251621 TI - Childhood tuberculous meningitis. PMID- 2251622 TI - Human babesiosis--a preliminary report of 2 suspected cases in South Africa. PMID- 2251623 TI - Current attitudes of members of SASOG to the present law on abortion. AB - 1. It is the opinion of 85% of the 289 gynecologists who replied to the questionnaire that the present Abortion Act should be reviewed. 2. At least 75% of respondents supported termination under the following circumstances: In a girl under age 14--85% In a girl under age 16--76% After failed female sterilisation- 78% 3. TOP 'on request' before 12 weeks was not supported by the majority (60%) and 93% were opposed to termination 'on request' after 12 weeks gestation. 4. The results of this survey were discussed by the Council of SASOG who agreed to the publication of the data but considered that only changes acceptable to at least 75% of the members could be supported by Council and that the minority viewpoint should also be respected. PMID- 2251624 TI - AIDS risk to health care workers. PMID- 2251625 TI - Smoking and lung cancer. PMID- 2251626 TI - Transplantation, fetuses and Parkinson's disease. PMID- 2251627 TI - The diagnosis and management of respiratory sleep disorders--the first 5 years at Groote Schuur Hospital. AB - While insomnia is a familiar management problem for most doctors, disorders of hypersomnolence are much less familiar. The evolution of sleep monitoring at a major South African teaching hospital is described and the classification of sleep disorders reviewed. Analysis of the first 5 years' experience revealed that 27 of 46 patients had sleep apnoea (all obstructive, but 13 with a central component), while 3 had narcolepsy. Contributing causes of sleep apnoea included obesity (25 patients), tonsillar enlargement (3), acromegaly (3), rheumatoid cervical spondylosis (1), Hunter's syndrome (1) and haemangioma of the throat (1). Death from sleep apnoea occurred in 3 cases. Treatment of specific causes was effective in abolishing sleep apnoea, although attempts at weight loss were effective in a minority only. Nasal continuous positive airway pressure was effective in achieving symptomatic relief. Sleep monitoring was found to be valuable, provided all-night study facilities are available, and provided that patients who simply snore are excluded by prior clinical evaluation. PMID- 2251628 TI - Lung cancer at Groote Schuur Hospital--a local perspective. AB - Over a 1-year period (1 January 1987-31 December 1987) 401 patients at Groote Schuur Hospital with newly diagnosed lung cancer were evaluated prospectively. The mean age of the patients was 59 years (range 31-87 years); 251 were coloured (62%), 100 white (25%), 47 black (12%) and 3 Asian (1%), and 280 were men (70%). Smokers numbered 378 (95%). The median delay between the onset of symptoms and presentation was 13 weeks (range 0-65 weeks). The commonest cell type was squamous--127 patients (34%), followed by adenocarcinoma 84 (23%), undifferentiated 78 (21%), small-cell 48 (13%), large-cell 29 (8%) and other types in 5 (1%). At the time of diagnosis 228 patients (57%) had evidence of metastases. Forty-six patients (11%) underwent surgery, 46 (11%) received chemotherapy, 141 (35%) radiotherapy and 168 (42%) symptomatic treatment as initial management. The overall 1- and 2-year survival rates were 18% and 8% respectively. PMID- 2251629 TI - Benzodiazepine use in a small community hospital. Appropriate prescribing or not? AB - Benzodiazepine (BDZ)-prescribing patterns in relation to indications and to drug characteristics in a small short-stay hospital were examined. In a sample of 800 patients, 183 were prescribed BDZs during their stay. Female patients received more BDZs (BDZ:female patients 1.31:1.0) than males (BDZs:male patients 1.02:1.0), particularly in the 21-40-year age group in which polypharmacy was highest. BDZs were classified according to their elimination half-lives. Our data showed that the majority fell into the long-acting (half-life greater than 24 h) (55%) and intermediate-acting (half-life 12-24 h) (20.7%) categories, despite the fact that most indications (pre-anaesthetic and night-time sedation; total 71.6%) called for the shorter-acting drugs. The merits or otherwise of this situation are discussed, and a number of questions put regarding the validity of this approach. Overall, BDZs accounted for 5.8% of the calculated medications given to the 800-patient sample. PMID- 2251630 TI - Vaccination--coverage of under-fives, validity of records, and the impact of mass campaigns in the Edendale/Vulindlela district of KwaZulu. AB - Recent epidemics of poliomyelitis and measles in the Edendale/Vulindlela district of KwaZulu spurred an investigation into the causes of vaccination failure. Vaccination coverage achieved by routine clinic services and by two mass campaigns was assessed. The validity of routine clinic vaccination records was also determined. Using a modified 30 x 7 random cluster sampling technique, 224 children aged 1-5 years were studied. Of these, 62% had a 'Road to Health' card. Best estimates show that 87% had had BCG, 62% three doses of diphtheria, pertussis and tetanus and polio, and 55% measles vaccine. The mass campaigns raised coverage for measles by 26%, and that for polio by 27%. Coverage estimates made from routine clinic data were consistently 13-25% higher than from this survey. This discrepancy is unfortunate, since it could lead to complacency if certain targets are apparently achieved using only clinic records, and points to the need for regular population-based surveys in all but the best organised health services. Inadequate vaccination coverage alone can explain the epidemics of polio and measles. The reasons for this, in the presence of an adequate clinic infrastructure, need to be assessed urgently to prevent further outbreaks. PMID- 2251631 TI - Measles vaccination coverage and its determinants in a rapidly growing peri-urban area. AB - A study was undertaken to ascertain the vaccination coverage of children aged 12 23 months living in Khayelitsha, a peri-urban township outside Cape Town, and to identify factors associated with measles vaccination coverage. A stratified proportional cluster sampling technique was used to select 46 clusters of 10 children each. Three strata were defined according to area of residence. The vaccination status of each child was determined from the preschool card. Usable information was obtained for 432 children; in 75.4% of cases the respondent was the child's mother, and 69.4% of children possessed a preschool card. Measles vaccination coverage was 63.5% (95% confidence interval 58-67%). Three factors had a significant association with incomplete measles vaccination: less than 6 months' residence in the area (odds ratio (OR) 3.1), having been born outside Cape Town (OR 2.5), and home delivery (OR 2.0). The mothers' level of education and children's age were not associated with measles vaccination status. Children in the New Shanty area were identified as a high-risk group. Carers of children in the New Shanty area were the least likely to know of the need for measles vaccination and to be visited by a community health worker. Greater efforts are required to identify high-risk children and areas. PMID- 2251632 TI - Synthetic laminaria tent for cervical ripening. AB - The efficacy and safety of a synthetic laminaria tent (Lamicel; Cabot) in ripening the cervix before induction of labour was compared with prostaglandin E2 (PGE2) oral tablets used intravaginally. Eighty patients were randomly assigned to use of the laminaria tent (N = 40) or PGE2 (N = 40). There were an equal number of primigravidas and multigravidas in each group. The only significant difference between the groups was the higher frequency of uterine hypertonicity (29 v. 5 : PGE2 v. tent) and consequent fetal distress (5 v. 1 : PGE2 v. tent) in the PGE2 group. However, the duration of labour was shorter in the PGE2 group than in the tent group (10, 14 h v. 11,61 h). These findings indicate that the synthetic laminaria tent is the preferred agent for cervical ripening in high risk pregnancies and in developing countries. PMID- 2251633 TI - [The influence of exercise-induced bronchoconstriction on participation in organized sport]. AB - Approximately 70-80% of all asthma sufferers develop acute airway obstruction with exercise, while at least 7% of children in the general population develop exercise-induced bronchoconstriction. The purpose of this study was: (i) to determine whether children in the Cape Peninsula who suffer from asthma and/or exercise-induced bronchoconstriction are as inactive and uninvolved in sport as asthmatic children in the USA; and (ii) whether this uninvolvement is a direct result of their susceptibility to exercise-induced bronchoconstriction. An in depth study was done on the intensity, frequency and level of participation in sport by children with asthma and/or exercise-induced bronchoconstriction compared with a control group of healthy children without a history of asthma or exercise-induced bronchoconstriction. Children with asthma and/or exercise induced bronchoconstriction generally maintained a similar level of sport participation as healthy children, and only children with serious asthma or exercise-induced bronchoconstriction experienced limitations with regard to physical activity. It was found that, in contrast to children in the USA, non participation in sport could not be explained by asthma and/or exercise-induced bronchoconstriction. PMID- 2251634 TI - The prevalence of exercise-induced bronchoconstriction in Cape Town schoolchildren. AB - An attempt was made to determine: (i) the prevalence of exercise-induced bronchoconstriction among white and coloured schoolchildren in Cape Town; and (ii) the validity of an exercise test for the diagnosis of asthma in the general population. Children (698 white and 494 coloured) were randomly drawn from schools in the northern suburbs of Cape Town. Each child participated in a standard 6-minute exercise test and spirometric measurements were taken before and 10 minutes after exercise with a portable spirometer. The diagnosis of asthma was based on a questionnaire and personal questioning and included those children who, in the past or at present, suffered episodic or continuous airflow obstruction, which was responsive to a bronchodilator. The criterion for the diagnosis of exercise-induced bronchoconstriction was a 10% decline in forced expiratory volume in 1 second after exercise. The prevalence of exercise-induced bronchoconstriction was significantly higher among white children (5.87%) than coloured children (4.05%). The sensitivity of the exercise test was 0.31 and the specificity 0.97. In contrast to the results of hospital-based studies, the negative predictive value of an exercise test (95%) was found to be greater than the positive predictive value (46%). It is therefore concluded that exercise testing is not a useful screening test for epidemiological use; it is probably useful as a challenge test for detecting asthma in the individual patient when the likelihood of the disease is high. PMID- 2251635 TI - A simple method of tattoo removal. AB - The use of trichloracetic acid in the treatment of decorative tattoos is described. The technique is simple to perform. No anaesthesia or analgesia is required. Complications are uncommon and usually minor. Trichloracetic acid acts by inflicting a chemical burn. PMID- 2251636 TI - Asthma and hyperthyroidism. A report of 4 cases. AB - For many years it has been known that thyrotoxicosis can worsen asthma, increasing both the frequency and severity of asthma attacks and increasing requirements for medication. Clinical recognition of this association may be difficult. Thyrotoxic asthmatics frequently experience side-effects from medications, particularly beta-receptor agonists and theophyllines. Four case reports of asthmatics in whom thyrotoxicosis was diagnosed are presented. All 4 patients improved on returning to euthyroid status. The mechanism responsible for the harmful interaction is not known. PMID- 2251637 TI - A 36-year-old man with complete heart block and shock. PMID- 2251639 TI - Diagnosis of tuberculosis. PMID- 2251638 TI - Fluoxetine-induced syndrome of inappropriate antidiuretic hormone excretion. PMID- 2251640 TI - The morbidity associated with traditional circumcisions. PMID- 2251641 TI - Aetiopathology of non-insulin-dependent diabetes. PMID- 2251642 TI - Management of non-insulin-dependent diabetes. PMID- 2251643 TI - Advances in hypertension associated with diabetes. PMID- 2251644 TI - Islet amyloid and type 2 (non-insulin-dependent) diabetes. PMID- 2251645 TI - [Myocardial function in patients with hereditary hemochromatosis based on echocardiographic data]. AB - In order to reveal changes in the myocardium at the preclinical stage of heart failure, 34 patients with hereditary hemochromatosis (HHC) underwent echocardiography in the M-mode. There were 26 men and 8 women aged 24 to 59 years. The control group was made up of 20 healthy persons. The HHC patients over 35 years of age (49.5 years on the average) manifested enlargement of the left ventricular cavity, an increase of the thickness of the interventricular septum and of the posterior heart wall, and reduction of pump function of the left ventricle. PMID- 2251646 TI - [Monoclonal immunoglobulinopathy in chronic active hepatitis and liver cirrhosis]. AB - The clinico-laboratory and morphological studies were performed to examine and characterize 15 patients with chronic active hepatitis and liver cirrhosis mainly of viral etiology, going in association with monoclonal immunoglobulinopathy. The diagnostic difficulties determined by the syndrome of monoclonal immunoglobulinopathy are demonstrated. The results of a long follow-up (up to 17 years) of the indicated patients' group are provided. A possible role is discussed of hepatitis B virus as a source of long antigenic stimulation in the origin of monoclonal immunoglobulinopathy in chronic diffuse diseases of the liver. PMID- 2251647 TI - [Combined radiation exposures and their immediate and late sequelae]. AB - The author reviews correlations between the general and local processes and criteria for the diagnosis of acute radiation sickness (acute radiation syndrome) /ARS/ as well as other clinical sequels of radiation injury (radiation burns, abnormalities of critical organ function, stochastic sequels) induced by total even and uneven radiation and concomitant radiation effects. Based on the own observations the coefficients were defined of private correlations of the doses of the total gamma- and high-absorbable ("soft") components of concomitant radiation effects on the content of neutrophil leukocytes in peripheral blood seen during successive transformations of the development of ARS and the subclinical forms of radiation injury. The main characteristic features of ARS induced by concomitant radiation injury as a result of nuclear reactor break down have been formulated. PMID- 2251648 TI - [Circulating immune complexes and the immune system in hemorrhagic vasculitis]. AB - The paper is concerned with the results of studying the concentration of circulating immune complexes and immune system (the number of lymphocyte populations and subpopulations in the peripheral blood, the level of serum immunoglobulins) in 45 patients aged 10 to 72 years with hemorrhagic vasculitis depending on the disease pattern and course before and after the treatment. The patients suffering from hemorrhagic vasculitis manifested appreciable changes in humoral immunity and negligible derangement of cellular immunity associated with dramatic enhancement of complex formation. The intensity of the alterations was discovered to be dependent on the pattern and course of the disease. PMID- 2251649 TI - [Toxic complications in bone marrow recipients]. AB - The authors provide the data on the rate and main clinical manifestations of toxic complications seen in bone marrow recipients in the early posttransplantation period. Analyze the causes of those complications. Give practical recommendations aimed at the prophylaxis of toxic complications and their early removal. PMID- 2251650 TI - [The megakaryoblastic variant of the blast crisis in chronic myeloleukemia]. PMID- 2251651 TI - [The combination of chronic lympholeukemia with other malignant neoplasms]. AB - Altogether 23 patients examined for secondary tumors at the All-Union Cancer Research Center of the USSR AMS underwent a clinical analysis. The overwhelming majority of the patients (17) were subjected to surgical intervention. Of these, none of the patients developed any postoperative complications or showed progress of chronic lympholeukemia (CLL). No relationship was noted between cytostatic treatment of CLL and origin of second tumors. No correlation was revealed either between the duration of CLL treatment and the incidence of second tumors origin. The authors provide a brief review of the literature on the given problem. Give a summary of the statistics of the CLL incidence in other malignant neoplasms. PMID- 2251652 TI - [The efficacy of combined chemotherapy in lymphogranulomatosis]. AB - Successive use of cyclic polychemotherapy according to the CVPP scheme before and after x-ray therapy made it possible to reach pronounced anticancer effect in the majority out of 58 patients with lymphogranulomatosis. It is recommended that the given treatment method be employed on a broader scale including the treatment of patients with the local disease patterns. PMID- 2251653 TI - [The late sequelae of the combined treatment of lymphogranulomatosis patients]. AB - As many as 107 patients with lymphogranulomatosis subjected to multimodality therapy were followed up for a long time. The rate of the occurrence of pneumofibrosis, alterations on the part of the cardiovascular system, the rate and causes of the development of hypothyrosis and herpetic infection are described. The cases of osteonecrosis of the head of the femur are reported. The efficacy of omento-oophoropexy and protection of the median part of the pelvis in preventing radiation-induced women's castration is appraised. PMID- 2251654 TI - [Goodpasture's syndrome]. AB - Two cases of Goodpasture's syndrome in men aged 68 and 58 years are described. The disease may go as a chronic relapsing process with rapid decompensation of renal functions and development of chronic renal failure after the patient's refusal to be given glucocorticoids. PMID- 2251655 TI - [The clinical significance of secondary erythrocytosis]. PMID- 2251656 TI - [Acute myeloid leukemias in elderly patients]. PMID- 2251657 TI - [Age-related differences in hematopoietic progenitor cells and the problems of carcinogenesis]. AB - In the past years the authors advanced a hypothesis of the "age-associated layers" of parent hemopoietic cells. The hypothesis was based first of all on the differences in the patterns of leukemias and noncancerous diseases (of the hemopoietic tissues) in children and adults. The nature of the changing age associated characteristics of parent cells remained obscure. Analysis of leukemias and epithelial tumors of radiation nature, formed in the victims to nuclear bomb explosion in Japan in 1945, analysis of leukemias occurring in persons with genetic diseases characterized by the known chromosomal aberrations (Down's syndrome, Louis-Bar syndrome, etc.), studies into the inherited forms of leukemias (chronic lympholeukemia, subleukemic myelosis, etc.--all these conditions are marked by the unstable genetic apparatus and high mutability) allowed the authors to make a conclusion about a kit of active differentiation genes which are replaced in health with age. Cancerous transformation may take place just at the level of those genes in parent cells with an unstable genome, since there appear specific mutation (in contrast to nonspecific ones characterizing the unstable genome) and a cancerous clone. PMID- 2251658 TI - [The regimen for corticosteroid use in acute lymphoblastic leukemia]. PMID- 2251659 TI - [The clinical importance of the radioimmunological determination of the beta 2 microglobulin in acute leukemia patients]. AB - The concentration of beta 2-microglobulin in the blood serum was examined in 141 patients with acute leukemia. There were 63 men and 78 women aged 14 to 78 years. Studies performed before chemotherapy was instituted revealed a statistically significant increase in serum beta 2-microglobulin in all varieties of acute leukemia as applicable to the control values. There was a considerable scattering of individual indicators of protein concentration in the serum, which did not allow the use of measurements of beta 2-microglobulin in the blood serum as a criterion for differential diagnosis in identification of certain clinicomorphological varieties of acute leukemia. A direct correlation was established between the concentration of serum beta 2-microglobulin and the phase of the disease. The data obtained indicate that the beta 2-microglobulin test is of great help for the control of remission completeness in acute leukemias and for early diagnosis of relapses. PMID- 2251660 TI - [A trial of the use of high doses of cytosar with autologous bone marrow protection in acute leukemias]. PMID- 2251661 TI - [The programmed treatment of acute leukemias]. PMID- 2251662 TI - [The determination of the D-arabinitol content of the blood serum--a method for the diagnosis and monitoring of an invasive candidal infection in cytopenia patients (preliminary data)]. AB - Gas chromatography was used to identify D-arabinitol over time (5-6 times on the average) in the blood serum of 24 patients with fever of unclear etiology. The patients were in a state of cytostatic and/or cytostatic and radiation cytopenia. In 20 donors, D-arabinitol was identified once. In the majority of the donors, that indicator did not exceed 1 microgram/ml, amounting on the average to 0.7 +/- 0.3. In patients with invasive candidiasis, the concentration of D-arabinitol surpassed 1 microgram/ml, reaching 4.0-5.5 micrograms/ml in some patients. In patients colonized with Candida, that indicator also exceeded 1 microgram/ml, not reaching, however, such high values as those seen in invasive candidiasis. Identification of the D-arabinitol level reflects the total activity of the fungi of the Candida genus contaminating the patients' mucous membranes at the moment of investigation irrespective of the process site, whereas monitoring allows one to follow tendencies of that activity and to correct therapy. PMID- 2251663 TI - [The respiratory therapy of acute respiratory failure in pneumonia in the presence of myelotoxic agranulocytosis]. PMID- 2251664 TI - [Recombinant alpha-interferon (reaferon) in the treatment of patients with chronic myeloleukemia]. AB - The authors relate the results of a clinical study of the Soviet recombination alpha-interferon (reaferon) in 46 patients with chronic myeloleukemia at different stages of the disease. Reaferon is shown to be tolerated well, to have a low percentage of side effects in particular high temperature and allergic reactions, to possess no hepato-, nephro- and cardiotoxicity. It has been proved that in patients with chronic myeloleukemia reaferon produces an independent antiproliferative effect and is capable of controlling the leukemic process without chemotherapeutic drug (in the stable chronic phase of the disease). Doses and administration of reaferon for a long time are suggested in order to prolong the disease course. PMID- 2251666 TI - [Para-amyloidosis of the internal organs in multiple myeloma]. PMID- 2251665 TI - [Local immunity in pathology of the IgA system (IgA subclasses in the saliva of patients with A-paraproteinemia)]. AB - In 39 patients with A-paraproteinemia, the local immunity status was estimated according to the level of IgA subclasses in the saliva and antibody activity of secretory IgA to E. coli and S. Sonnei. Local production of normal IgA was undisturbed only in 12 patients with A-paraproteinemia, since in the saliva of those patients, there was a normal correlation of IgA subclasses and the level of antimicrobial IgA antibodies was the same as in healthy persons. The overwhelming majority of the patients with A-paraproteinemia and all the patients suffering from heavy alpha-chain disease manifested deficiency of local production of normal IgA, which consisted in the impairment of the normal correlation of IgA subclasses in the saliva and in the reduction of sIgA function. A-paraprotein was detected in many samples of the saliva using agar electrophoresis followed by immunoblotting. Secretion was shown to be mainly penetrated by the polymeric forms of A-paraprotein. PMID- 2251667 TI - [The diagnostic importance of echography of the spleen, abdominal lymph nodes and vessels in chronic lympho- and myeloleukemias]. AB - Echography of the spleen and abdominal vessels was performed in patients with chronic myeloleukemia (CML) and chronic lympholeukemia (CLL). The patients belonging to these groups manifested enlargement of the spleen, alterations of its echo structure and dilatation of the vessels even at the initial disease stage. Appreciable splenomegaly with a proportional increase of the diameter of the main vessels of the abdominal cavity and derangement of the splenic echo structure were ascertained in patients in the stage of pronounced clinicohematological manifestations. Moreover, provided those diseases run an atypical course, echography of the spleen, abdominal lymph nodes and vessels is of differential diagnostic importance. As compared to patients with CLL, the spleen of those with CML differed as regards the extent of enlargement and alterations in the organ structure in different stages of the tumorous process. There were differences in the diameter of the abdominal vessels. The patients with CML demonstrated splenic infarctions of different standing whereas patients with CLL conglomerates of the abdominal lymph nodes. In patients with CML, remarkable splenomegaly was observed more frequently. Echography of the spleen and vessels in patients with CML and CLL is a highly informative, noninvasive and safe method which is likely to be widely used in hematology. PMID- 2251668 TI - [The pulmonary manifestations of lymphogranulomatosis]. PMID- 2251669 TI - [The polychemotherapy and combined treatment of patients with stage-I and -II lymphogranulomatosis and unfavorable prognosis]. AB - As many as 104 patients with lymphogranulomatosis, clinical stages I-II, having an unfavourable prognosis were examined for the efficacy of polychemotherapy and combined treatment. Polychemotherapy was received by 47 patients, combined treatment (chemo- plus radiotherapy) by 57 patients. Complete remissions were attained significantly more often in patients given combined treatment (92%) as compared to patients on polychemotherapy alone (64%). After complete remissions relapses occurred in 60% of the patients on polychemotherapy and in 13% of the patients receiving combined treatment. The 7-year survival without any relapses was significantly higher (85%) in patients on combined therapy as compared to patients given polychemotherapy (36%). However, the 10-year survival appeared the same in both the groups (87 and 88%). Splenectomy affected neither the rate of relapses in both the groups nor the immediate treatment efficacy or survival. PMID- 2251670 TI - [The comparative efficacy of splenectomy and antilymphocyte globulin therapy in patients with aplastic anemia]. AB - Analysis of the clinical efficacy and long-term survival of patients with grave and not grave forms of aplastic anemia, subjected to splenectomy or treated with antilymphocytic globulin has shown that in grave aplastic anemia, the clinical efficacy of antilymphocytic globulin is higher than the efficacy of the operative treatment methods. The 30-month survival can be attained in 42% of the patients given globulin and in 28% of the patients after splenectomy. In patients with grave aplastic anemia, it is recommended that the treatment be instituted from the use of antilymphocytic globulin in a dose of 15 mg/kg bw daily for 5 days, provided there are no contraindications. In patients with not grave aplastic anemia, the results of splenectomy and therapy with antilymphocytic globulin are approximately the same: the 5-year survival amounts to 94 and 93%, respectively. Therefore, the use of globulin may be recommended as a method of choice for the above patients' group, since surgical approaches to the treatment are still coupled with a high risk for the patient's life. PMID- 2251671 TI - [The advisability of modifying the current outline of blood coagulation]. AB - The necessity of modifying the scheme of blood coagulation employed in the practice of clinicians is determined by the fact that the schemes offered before were short of the following important moments: 1) the whole totality of the mechanisms of factor VII activation (by factors III, XIIa, IXa, Xa, IIa, phospholipids and lipoproteins) and importance of its activation and increase of the level to reveal the risk of the development of the DIC syndrome, thromboses, sudden cardiac death; 2) formation during transformation of fibrinogen to fibrin of high molecular weight complexes of fibrin monomers (stabilized and not stabilized by factor XIIIa), whose presence in the blood plasma and serum provides important evidence for intravascular coagulation; 3) peptide splitting from prothrombin (fragments 1, 2) and fibrinogen (peptides A and B, 1-42, 15-42) the determination of which is also used for revealing activation of the blood and fibrinolytic system. Those and a number of other characteristic features are taken into account in the scheme of blood coagulation offered by the authors. A scheme of the functioning of the main anticoagulant mechanisms (antithrombin III and heparinoids; thrombomodulin, the system of proteins C and S) is also provided. PMID- 2251672 TI - [Variant forms of von Willebrand's disease]. AB - Abnormalities of platelet and plasma Willebrand's factor produce noticeable effects on the clinico-laboratory manifestations of Willebrand's disease. This is confirmed by more pronounced gravity of the hemorrhagic syndrome, the lack of the correcting effect in response to physiological conditions (pregnancy) and administration of DDAVP in contrast to beneficial effect seen in patients with normal content of Willebrand's factor in platelets. PMID- 2251673 TI - [Hemostasis in influenza and acute respiratory viral infections in the middle aged and elderly]. AB - Hemostasis was examined over time in 168 patients with influenza and ARVI. There were 53 elderly patients, 54 senile patients and 4 long-livers. 57 patients under 60 years made up a reference group. The patients with influenza did not differ significantly from those with ARVI as regards hemostasis. The elderly persons manifested pronounced acceleration of phases I-II blood coagulation. In the acute disease period, the old men demonstrated high platelet aggregation, whereas during convalescence, activation of the plasmic component of hemostasis in the presence of relatively low antithrombin III. Analysis was also made of the age associated changes in hemostasis depending on influenza and ARVI complications (pneumonia, exacerbation of coronary disease, bronchitis). The changes revealed dictate the necessity of hemostasis control in elderly and senile persons afflicted with influenza and ARVI. PMID- 2251675 TI - Alteration of renal amino acid transport system in cadmium-intoxicated rats. AB - Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria. PMID- 2251674 TI - Glutathione conjugate mediated toxicities. AB - Glutathione (gamma-glutamyl-L-cysteinylglycine: GSH) is present in high concentrations in most living cells and participates in a variety of vital cellular reactions. In particular, GSH protects cells from potentially toxic electrophiles formed via the metabolism of xenobiotics, and such reactions have long been associated with the process of detoxication (Baumann and Preusse, 1879; Jaffe, 1879). Compounds that form GSH conjugates are processed by gamma-glutamyl transpeptidase (gamma-GT) and dipeptidases to cysteine S-conjugates, which are usually excreted in urine as their corresponding mercapturic acids (S-substituted N-acetyl-L-cysteine conjugates). In addition, GSH peroxidase activity, whether catalyzed by the selenium-dependent GSH peroxidase or by the GSH S-transferases, serves to detoxify hydrogen peroxide and organic hydroperoxides. However, in recent years, evidence indicating that GSH conjugation plays an important role in the formation of toxic metabolites from a variety of chemicals has accumulated. Thus, several classes of compounds are converted, via conjugation with GSH, into either cytotoxic, genotoxic, or mutagenic metabolites. The purposes of the symposium on "Glutathione Conjugate Mediated Toxicities" presented at the 1990 Society of Toxicology Annual Meeting were to discuss recent findings in this rapidly moving field, to present ideas on the mechanisms and modulation of GSH conjugate-dependent toxicities, to present a consensus on the broader significance of this work, and to identify directions for future research. This paper summarizes these presentations. GSH conjugation reactions are involved in the bioactivation of several classes of xenobiotics, and four types of GSH dependent bioactivation reactions can be identified: (1) directly toxic GSH conjugates may be formed from vicinal dihaloalkanes via formation of electrophilic sulfur mustards; (2) cysteine conjugate beta-lyase-dependent bioactivation is involved in the selective nephrotoxicity of haloalkenes; (3) GSH conjugates of hydroquinones and isothiocyanates may serve as transport and targeting metabolites; and (4) GSH-dependent reactions may be involved in the release of toxic agents from precursor organic thiocyanates and nitrosoguanidines (N-methyl-N'-nitro-N-nitroguanidine). PMID- 2251676 TI - Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation. AB - The mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases testosterone (T) secretion without significantly altering plasma luteinizing hormone (LH) concentrations was investigated. Testes from sexually mature Sprague-Dawley rats dosed 7 days earlier with 100 micrograms TCDD/kg secreted 30-75% less T than did testes from control rats when perfused in vitro with the LH analog human chorionic gonadotropin (hCG). This decrease confirms that testicular responsiveness to LH, the hormone which regulates T secretion in vivo, is impaired by TCDD treatment. Because TCDD also reduced intratesticular T content, the decrease in T secretion is due to an inhibition of T synthesis rather than to a failure of the secretion process. These effects of TCDD are not secondary to undernutrition, because perfused testes from feed-restricted control rats were fully hCG responsive. TCDD treatment neither increased the hCG stimulated secretion of any T precursor nor significantly decreased the efficiency with which testes converted the pregnenolone (PREG) they synthesized into T (PREG is the initial steroidogenic intermediate). In addition, TCDD did not inhibit T secretion when steroidogenesis was supported by exogenous PREG at approximately the in vivo rate. We conclude that TCDD does not inhibit the conversion of PREG to T. The inhibition of T biosynthesis must instead result from an inhibition of PREG formation. The finding that TCDD treatment substantially decreased the rate at which hCG-perfused testes secreted PREG and its metabolites (a decrease seen across all hCG concentrations) confirms this conclusion. This inhibition of LH/hCG-stimulated PREG formation by TCDD must be due to a reduction in the activity of the enzyme which converts cholesterol to PREG (cytochrome P450scc), and/or an impairment in the multistep process responsible for mobilizing cholesterol to this enzyme. PMID- 2251677 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced oxidative stress in female rats. AB - Oxidative stress may play a role in the toxic manifestations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Therefore, the time-dependent effects of 100 micrograms TCDD/kg on various indices of oxidative stress including lipid peroxidation. DNA damage, membrane fluidity, calcium homeostasis, nonprotein sulfhydryl content, and NADPH content of hepatic subcellular fractions of female rats were followed for 12 days. Increases in lipid peroxidation of 400-500% occurred in mitochondrial and microsomal membranes and nuclei, with maximum increases occurring 5-6 days post-treatment. Decreases in the nonprotein sulfhydryl content of mitochondrial and microsomal fractions of approximately 80% were observed by Day 12 posttreatment. Membrane fluidity gradually decreased following administration of TCDD, with decreases of 30-40% being observed in mitochondria, microsomes, and plasma membranes. A sharp increase in the incidence of hepatic nuclear DNA single strand breaks was observed 3 days after treatment with an increase of approximately 600% by Day 9. Following the administration of TCDD, increases of 70-80% occurred in the calcium content of mitochondria and microsomes. An 18% increase in cytosolic calcium was present 12 days after the administration of TCDD. Cytosol and mitochondria both exhibited an initial increase in NADPH content following administration of TCDD, but by Day 12 both had decreased to approximately two-thirds of control values. The results clearly demonstrate that TCDD administration induces an oxidative stress in rat liver. The most pronounced effects were observed in membrane lipid peroxidation and DNA damage with gradual changes being observed in calcium and nonprotein sulfhydryl contents and membrane fluidity. PMID- 2251678 TI - The effects of mercuric chloride on transport by brush border and basolateral membrane vesicles isolated from rat kidney. AB - Both brush border and basolateral membrane vesicles were prepared from rat kidney by Percoll gradient centrifugation. The addition of mercuric chloride (100 nM) to vesicles prepared from healthy, male, Sprague-Dawley rats reduced p aminohippurate (PAH) transport by basolateral vesicles. No effect was observed on glucose transport by brush border vesicles even at mercuric chloride concentrations as high as 10 microM. However, when the metal salt was added in the presence of 5% bovine serum albumin, basolateral PAH transport was unaffected. Transport studies also were done with vesicles isolated from rats pretreated with mercuric chloride (4 mg/kg, sc). Transport of PAH was unaffected at all times studied. Glucose transport was unaffected at 1 and 3 hr, but at 16 hr was reduced significantly. By 48 hr, brush border glucose transport had recovered. These data demonstrate that mercuric chloride can alter renal membrane function, and that the effects depend on the membrane vesicle population used. With pretreatment studies, the time after treatment also influences whether or not an effect is seen. PMID- 2251679 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat is not a direct effect on feed intake regulation in the brain. AB - The most striking sign of acute toxicity of TCDD in animals is a progressive reduction of feed intake, accompanied by loss of body weight eventually resulting in death. The mechanism(s) of this voluntary feed refusal is (are) not known but it is generally accepted that both centrally and peripherally (via feedback) acting anorectic agents exert their effect(s) in the hypothalamus. In this study direct administration into the lateral cerebral ventricle of rats resulted in much higher concentrations of TCDD in the hypothalamus and also in other regions of the brain than after a lethal intravenous (iv) injection. While rats injected iv displayed the expected cachectic syndrome, intracerebroventricularly (icv) dosed animals ate and gained weight normally. These findings preclude the possibility of a direct effect of TCDD on appetite-regulating areas of the brain. Moreover, these results require the assumption that the appetite suppressive effect of TCDD is due to a (feedback) mechanism originating in the periphery. PMID- 2251680 TI - Opiates depress ACh and ATP release from cholinergic synaptosomes by blocking calcium uptake. AB - We have studied the effects of opiates on ATP and acetylcholine (ACh) release from cholinergic nerve terminals isolated from the electric organ of Torpedo marmorata. The release of ATP was inhibited by morphine and this action was reversed by naloxone. Morphine, [D-Met2-Pro5]enkephalinamide and [D-Ala2 Leu5]enkephalin also inhibited acetylcholine release. Naloxone prevented these inhibitory effects. The action of enkephalin on ACh release was less effective than that of morphine. The calcium uptake by nerve terminals of Torpedo electric organ was also inhibited by morphine, either under resting or depolarizing conditions, and this effect was reversed by naloxone. Using the quick freeze fracture method, the structural changes induced by morphine in the presynaptic membrane were also studied. Morphine prevents the rearrangement of intramembrane particles (IMPs) at both freeze-fractured faces of the synaptosomal presynaptic membrane after depolarization. It is concluded that opiates depress the ATP and the ACh releases from cholinergic synaptosomes by inhibiting the calcium uptake by the nerve terminals and the rearrangement of the IMPs after potassium-induced depolarization. Furthermore, ACh release, but not ATP release, seems to be related with the rearrangement of IMPs in the presynaptic membrane. PMID- 2251681 TI - Eseroline, a metabolite of physostigmine, induces neuronal cell death. AB - The toxic effects of physostigmine, an anticholinesterase drug, and its metabolite eseroline were investigated in three neuronal cell culture systems, mouse neuroblastoma N1E-115, rat glioma C6, and neuroblastoma-glioma hybrid NG 108-15. Physostigmine and eseroline (0.5 nM) elicited a time-dependent leakage of lactic acid dehydrogenase (LDH) from all three cell types. An increased release of [14C]adenine nucleotides was also detected from cells when they were prelabeled with [14C]adenine. Eseroline was comparatively more toxic than the parent compound, physostigmine. Eseroline elicited a dose- and time-dependent leakage of LDH and release of adenine nucleotides from the neuronal cells. A nonneuronal cell line, rat liver ARL-15, was comparatively the most resistant cell type to eseroline toxicity. The concentrations of eseroline needed for 50% release of adenine nucleotides or 50% leakage of LDH from NG-108-15 and N1E-115 cells in 24 hr ranged from 40 to 75 microM. The concentrations of eseroline needed to obtain similar responses in C6 and ARL-15 cells were much higher and ranged from 80 to 120 microM. Phase contrast microscopy showed extensive damage to three neuronal cell lines at concentrations of eseroline as low as 75 microM. The loss of ATP from N1E-115 cells exceeded 50% when they were treated with 0.3 mM eseroline for 1 hr--at which time the leakage of LDH was not detectable. It seems that eseroline causes neuronal cell death by a mechanism involving loss of cell ATP. Thus, the formation of eseroline may contribute to the toxic effect of physostigmine. PMID- 2251682 TI - Lack of changes in cytosolic ionized calcium in primary cultures of rat kidney cortical cells exposed to cytotoxic concentrations of gentamicin. AB - Gentamicin nephrotoxicity in vivo has a delayed onset. Our assessment of gentamicin-induced cell death in vitro, by measuring the release of cytosolic lactate dehydrogenase (LDH), indicated a prolonged onset as well. A recent study, which showed that gentamicin caused an abrupt increase in the concentration of cytosolic free calcium ([Ca2+]i) in a trypsin-harvested kidney cell line, suggested that immediate changes in calcium homeostasis may initiate the pathogenesis of gentamicin nephrotoxicity. To study the immediate effect of gentamicin on [Ca2+]i, gentamicin was perfused for 1 hr over primary monolayer cultures of renal cortical epithelial cells, and suspensions of trypsin-harvested renal cells (from primary cultures and a cell line) were treated with gentamicin for 30 min. [Ca2+]i was determined using the fluorescent probe fura-2. Positive controls (ionomycin and mercury) reliably increased [Ca2+]i in each experimental model, but no increase in [Ca2+]i was observed with gentamicin. Because enzyme release data indicated that significant cytotoxicity did not occur until 48 hr of exposure to 2 mM gentamicin, primary cultures were exposed to gentamicin (1-2 mM) for 24-48 hr and [Ca2+]i was measured. No gentamicin-induced increase in [Ca2+]i was observed in these longer exposures, whether or not significant LDH release occurred. These results do not support a role for elevated [Ca2+]i in the cytotoxicity of gentamicin in cultured kidney cells, either immediately after exposure or following prolonged exposures. PMID- 2251683 TI - Atropine inhibition of the cardiodepressive effect of mono(2-ethylhexyl)phthalate on human myocardium. AB - Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer in polyvinylchloride (PVC)-derived plastic. Mono(2-ethylhexyl)phthalate (MEHP), the major metabolite of DEHP, had a reversible, concentration-dependent (15-200 micrograms/ml) negative inotropic effect on a human in vitro atrial trabecular isometric preparation with an IC50 of 85 micrograms/ml. When atropine (22-32 micrograms/ml) was included in the atrial preparation the IC50 was shifted to greater than 120 micrograms/ml, suggesting that MEHP acts in part through the cholinergic receptors. PMID- 2251684 TI - Effects of novel antioxidants on carbon tetrachloride-induced lipid peroxidation and toxicity in precision-cut rat liver slices. AB - Previous studies in rat liver microsomes have demonstrated the effectiveness of the 21-aminosteroid, U-74,006F, the troloxamine, U-78,517G, and N,N'-diphenyl-p phenylenediamine (DPPD) in preventing carbon tetrachloride (CCl4)-induced lipid peroxidation. Studies reported here utilized liver slices to assess whether these antioxidants could prevent lipid peroxidation and ensuing toxicity in a more complete/complex system. Liver slices prepared from Aroclor 1254-induced SD rats were incubated in Dulbecco's modified eagle media, 37 degrees C, for up to 9 hr. Slices were preincubated with test compounds for 30 min prior to addition of CCl4. Lipid peroxidation, as measured by the formation of thiobarbituric acid reactive substances and ethane evolution, was decreased by U-74,006F (100 microM), U-78,517G (100 microM), and DPPD (1 microM). CCl4 (2.5 microliters) decreased intracellular K+ content, intracellular lactate dehydrogenase (LDH), and intracellular isocitrate dehydrogenase (ICD) activities over a 9-hr incubation period. Despite the marked effects on lipid peroxidation, U-74,006F showed no protection against K+ or LDH loss and only moderate protection against ICD loss. U-78,517G showed no protection against K+ loss but substantial protection against enzyme loss. DPPD demonstrated slight protection against K+ and marked protection against enzyme loss. All three compounds inhibited CCl4 induced lipid peroxidation; U-78,517G being most effective, followed by DPPD and U-74,006F. Inhibition of lipid peroxidation provided protection to the membrane structure as indicated by inhibition of LDH and ICD loss. The antioxidants failed to protect against CCl4-induced toxicity (K+ loss). These results suggest that CCl4-induced lipid peroxidation and toxicity may be dissociable. PMID- 2251685 TI - [The vascularization of the autograft in different states of the recipient bed based on data from the superselective angiography of a canine mandibular preparation]. AB - Superselective angiography of mandibular preparations from 72 dogs has revealed that the inferior alveolar artery, tied up by a routine method, does not take part in the transplant revascularization. Binding of an intraosseous or transplanted facial artery stump with a heparin plug has revealed recanalizing vessels in the transplant, that speed up its restructuring. PMID- 2251687 TI - [A comparative study of the effectiveness of the analgesic effect of electropuncture stimulation and nonnarcotic analgesics in therapy patients in an emergency dental care office]. AB - Analysis of patients' subjective sensations, of rheography and electro odontometry data has lead the authors to a conclusion that the analgesic effect of rengasil was higher than that of ibuprofen and that rengasil combination with electropuncture was still more effective. The analgesic effect was the most marked in alveolitis and periodontitis, less so in inflammations of the pulp, and no effect could be achieved in acute purulent pulpitis. The authors suppose that pain syndrome alleviation after electropuncture stimulation and after administration of anti-inflammatory drugs is explained mainly by changed hemodynamics at the site of inflammation, this resulting in reduction of the edema and in diminished effects of biochemical substances released in the course of inflammation. PMID- 2251686 TI - [A new siloxane material for eliminating defects of the soft facial tissues by an injection method. I. The laboratory and experimental research]. AB - The authors present the results of laboratory and clinical analysis of vinyl siloxane polymer-based compositions, Pt catalyzer-hardened. Animal experiments have demonstrated high biologic inertness of the implantation material, inducing virtually no irritation of the adjacent tissues. These results confirm the possibility of clinical use of this new material. PMID- 2251688 TI - [The index assessment of periodontal status in the combined treatment of patients with generalized periodontitis]. AB - The authors compare the periodontal status in 94 patients with moderate periodontitis over the course of treatment making use of various splint designs and without splints. The status of the periodontium was assessed basing on the time course of indexes. Administration of various multiple-modality treatment schemes resulted in improvement of the periodontal clinical status in all the patients, though the efficacy of the therapeutic measures was different. The improvement in respect of all the examined parameters was the most manifest only in the group of patients treated with fixed splints with parapulpal fixation or with those pickling-based. PMID- 2251690 TI - [Image distortions occurring on intraoral dental x-rays and the ways to overcome them]. AB - Typical errors occurring in roentgenography of the teeth were simulated in a series of experiments. The results evidence that erroneous centering and angle of the x-ray tube inclination, incorrect centering of the film lead to disproportionate distortion of the shape, size, and position of all anatomical elements, that make the results of x-ray examination unreliable. Standardization of methods of intraoral roentgenography implies strict adherence to the rules of roentgenogram recording and treatment; this will permit obtaining high-quality roentgenograms and reduce the x-ray load of the patients. PMID- 2251689 TI - [The utilization of the influence of pathological factors on the status of the periodontal tissues of the mandible]. AB - A quantitative assessment of the influence of local and general factors on the development of pathologic processes in the periodontium is given for the first time. Factors characterized by the highest influence are distinguished. Mathematical analysis was based on information theory. PMID- 2251691 TI - [The dynamic biochemical indices of the blood in patients with suppurative inflammatory processes of the soft tissues of the face and neck]. AB - Changes in the blood serum protein and mineral composition, trypsin inhibitor content, alanine amino-transferase, aspartate aminotransferase, alpha-glutamyl transpeptidase, creatine kinase, choline esterase activities, blood plasma trace element levels were examined in 112 patients with pyoinflammatory involvement of the soft tissues of the face and neck. The study was revealed reduced blood serum albumin concentration, elevated trypsin inhibitor levels and alpha-glutamyl transpeptidase and creatine kinase activities, decreased content of Mg and Zn and, in some patients, of choline esterase activity. Biochemical parameters gradually normalize, as the patients recover, their normalization depending on the therapeutic methods and detoxication treatment. PMID- 2251692 TI - [The pathogenetic aspects of the effect of hypoxia on the trigger mechanisms of suppurative-inflammatory complications in patients with combined maxillofacial and craniocerebral trauma]. AB - Study of the relationship between the time course of secondary tissue hypoxia development and changes in the neutrophilic phagocytic activity, which was carried out in 65 patients with combined maxillofacial and craniocerebral injury, has revealed a detrimental effect of hypoxia on antibacterial defense factors of the body, this effect being conductive to development of pyoinflammatory complications; this should be borne in mind when planning treatment strategy. PMID- 2251693 TI - [The clinical value of the middle-molecule metabolite index in assessing the severity of the intoxication syndrome in patients with maxillofacial phlegmons]. AB - A total of 74 patients with maxillofacial phlegmons were followed up. The examinations have revealed a relationship between the severity of the intoxication syndrome and signs of a local inflammatory process, on the one hand, and peripheral blood leukocyte count, leukocytic index of intoxication, and level of medium molecular mass metabolites, on the other. The latter index was the most objective indicator of the severity of the body intoxication. The authors claim that this index may become a valuable diagnostic test in the assessment of body intoxication in patients with maxillofacial assessment of body intoxication in patients with maxillofacial inflammatory processes, of the time course of these processes, of the treatment efficacy and prediction of their outcome. PMID- 2251694 TI - [The bacterial associations in maxillofacial actinomycosis]. AB - A variety of clinical forms of actinomycosis, difficulties of its early diagnosis and particularly of the differential diagnosis between this condition and tuberculosis, nocardiosis, aspergillosis necessitate the development of present day methods for the early laboratory diagnosis of actinomycosis. Basing on the data on present-day methods for isolation of anaerobic and microaerobic diphtheroids, the authors characterize the bacterial associations occurring in maxillofacial actinomycosis and other odontogenic processes, discuss problems in isolation and identification of Actinomyces cultures. PMID- 2251695 TI - [The late treatment results in cancer of the lower lip]. AB - Analysis of late results of treatment of carcinoma of the lower lip in 106 patients followed up for 4-5 years has confirmed that these results are worse if a patient consults a doctor late and if the process is disseminated. Our data evidence that late results do not depend on the method used to manage the primary focus on the lip, though radiotherapy may be considered as the optimal treatment modality. Histologic study of operation material after preventive surgery has not revealed metastases to regional lymph nodes, therefore if the lymph nodes are clinically intact, a dynamic follow-up is recommended after the primary focus is cured. PMID- 2251696 TI - [The effect of toothbrushes on human dental enamel and dentin wear]. AB - The authors compare the effects of natural (porcine) and synthetic (Toinex, USA, and Eschalon, France) bristle and rough toothbrushes on the tooth enamel and dentin in the course of toothbrushing. No abrasive effects were detected when brushing normal teeth in clear water. The rate of enamel and dentin abrasion in tooth powder or tooth paste suspension depended on the shape of bristle cut and particularly on the toothbrush roughness. PMID- 2251697 TI - [The assessment of the course of the wound process after surgical interventions on the soft tissues of the face and neck by indices of the free-radical oxidation of the peripheral blood]. AB - Interventions in surgery on soft tissues of the face and neck cause a nonspecific response of the body, which mobilizes functioning of the enzymic antioxidative complex. Pyoinflammatory complications in the postoperative period are associated with impairment of the total antioxidative mechanism of the body. These data may be useful in the early diagnosis of complications and in the development of a pathogenetic strategy for the prevention and treatment of postoperative wounds. PMID- 2251698 TI - [A new myoplasty method using the temporal muscle and cartilage allograft with the perichondrium]. AB - The authors have for the first time achieved good results in experimental operations performed in 2 cadavers and 8 laboratory animals. A female patient suffering from progressive facial hemiatrophy was operated on with good results. The authors have revealed that facial deformation associated with Parry-Romberg's syndrome may be eliminated by myoplasty with the temporal muscle combined with transplantation of the allocartilage covered with perichondrium. PMID- 2251699 TI - [The diagnosis of sialolithiasis taking into account the stage of the pathological process]. AB - A total of 142 patients with sialolithiasis were examined, treated, and followed up. Analysis of clinical manifestations and morphologic changes has revealed a staged pattern of this condition, depending on the sialolith localization, disease standing, and incidence of inflammation exacerbations. The authors consider that a profound study of clinical symptoms with the use of mathematical statistics methods permits a sufficiently accurate identification of the histologic stage of the process and helps define the scope of surgical intervention. PMID- 2251700 TI - [Changes in the amount of gingival fluid after tooth preparation and the reinforcement of bridgework made from different alloys]. AB - Preparation of dental hard tissue and fortification of dentures made of NiCr steel and NiCr steel coated with titanium nitride activate gingival fluid secretion. Gold and silver-palladium alloys decrease gingival fluid secretion and promote alleviation of the inflammatory process. PMID- 2251701 TI - [The diagnostic value of epicutaneous tests in intolerance for dentures made of stainless steel]. AB - A total of 19 patients with stainless denture intolerance were examined. In addition to the routine stomatological examination, the authors determined pH of mixed saliva, measured the steady-state potentials of dentures, and performed epicutaneous tests with samples made of stainless steel, chromium and nickel. In all the patients, the epicutaneous tests with chromium and/or nickel were positive, those with stainless steel were negative. Abnormal reactions can be accounted for by the influence of an electroplating factor in 8 patients and by an allergic factor in 6. It is impossible to explain the pathogenesis of intolerance in 3 patients. Replacement of the dentures by those made of other material resulted in full recovery. Terminological aspects are also dealt with in the present paper. PMID- 2251702 TI - [The late results of using fixed dentures made of stainless steel with a titanium nitride-based finish coating]. AB - Forty-four patients fitted with fixed dentures made of stainless steel with TiN based decorative coating were followed up for 2 years. Abrasion of the decorative coating at the site of the crown contact with the basis and clammers of plate dentures and at the site of cutting edges of frontal teeth was recorded in 11 (25 percent) subjects. Measurements of the electric potentials have revealed their essential increase in the patients fitted with dentures with TiN-based coating vs. those with dentures made of gold and steel. PMID- 2251703 TI - [An evaluation of the quality of the fabrication of removable plate dentures by the histamine content in mixed saliva]. AB - Clinical and laboratory study, aimed at development of an objective criterion that would permit assessment of the quality of plate dentures early after orthodontic treatment, was carried out in 66 subjects aged 45 to 74 years. The examinations carried out before and after orthodontic treatment revealed a relationship between histamine concentrations in the background salivary pool and the presence of inflammation signs in denture bed tissues in the first days after plate denture application. The detected relationship may be regarded as an additional objective criterion permitting assessment of the denture quality in early periods after orthodontic treatment. PMID- 2251704 TI - [Changes in the immune system of patients with dental implants made of different materials]. AB - To assess the immune system status, the authors have measured various lymphocyte populations, whose ratio was determined in indirect immunofluorescence with Ortho or BL monoclonal antibodies, CD3, CD4, CD8, and DR-specific. The detected shifts in the immunity system permitted dividing the patients into 3 groups: Group 1 consisting of subjects with moderate immunity depression, Group 2 including those with moderate immunity stimulation, and Group 3 comprising patients with poorly manifest changes in the immunity system. The authors recommend carrying out analyses of the immunity system before and after implantation surgery, for such analyses may help predict possible complications and improve therapeutic correction thereof. PMID- 2251705 TI - [The biomechanical characteristics of the instruments for preparing the bone bed for cylindrical implants]. AB - The author has studied the instruments used for osseous bed preparation for a cylindrical implant in respect of their heating the bone, time of boring, and pressure on the instrument. 21 cadaveric mandibles were used in the study. Round and fissure bursa and a drill were compared at rotation velocities of 1000 to 7000 r.p.m. and pressure of 5 and 10 mg Hg; bone temperature was measured at a distance of 0.5 cm from the drilling site. Drilling with round and fissure bursa was found to essentially heat the bone. The optimal instrument as regards the least heating, pressure on the instrument, and the most rapid drilling was found a drill with a rotation speed of 1000 r.p.m. PMID- 2251706 TI - [The results of sanitary chemical research into denture base materials coated with components from essential-oil plants]. AB - Examinations of the basic material for removable dentures, coated with rose, lavender, sage wax evidence that such coating essentially reduces residual methylmetacrylate migration and its side effect on the denture bed tissues, and improves the hygienic characteristics of dentures. Modification of the basic material by introducing Sklariol into the polymer considerably reduces the residual monomer migration. These results recommend coating of essential-oil plant wax for the prevention of denture bed tissue inflammations. PMID- 2251707 TI - [The electrical excitability of the neuroreceptor apparatus of the pulp in the intact teeth of patients with chronic alcoholism]. AB - The aim of the study was to develop rapid methods for tentative diagnosis of chronic alcoholism. For this purpose 50 patients, male and female ones, suffering from chronic alcoholism were examined for electroexcitability of their intact teeth pulp nerve receptor system. Initial examination revealed reduced the threshold of tooth pulp electroexcitability as against the control. Drastic variations in electroexcitability values of neighbouring teeth were noted. The parameter studied was found perverted in 52 percent of the alcoholics. This characteristic improved by the patient's discharge from hospital, though in the majority of cases the regularities cited above persisted. PMID- 2251708 TI - [Structural research on silicate dental materials]. AB - Comparative studies of the structural features of Gamma porcelain, Sikor glass ceramic, and Cast Glass Ceramic (CGC) by x-ray structural analysis and IR spectroscopy have revealed that improvement of the physical characteristics of stomatological silicate material in transition to glass ceramic is explained by similarity of their composition with lithium disilicate. CGC structure due to convergence of the composition of the major areas of chemical heterogeneities is the most compact as compared to Sikor structure and more so us. Gamma. As evidenced by IR spectroscopy, super microhardness of CGC, observed in practice, appears to be related to their higher solidity in contrast to that of Gamma porcelain, structurally similar to amorphous silica, and that of Sikor characterized by a poorly crystallized tridymite structure. Higher physical characteristics of CGC distinguish it among the known silicate materials used in dentistry and recommend it for wide practice. PMID- 2251709 TI - [The orthodontic indications for the removal of individual permanent teeth in treating distal bite]. AB - A follow-up of 28 patients with permanent distal occlusion, aged 11 to 15 years, and analysis of the results of their treatment have demonstrated that maxilla underdevelopment in the frontal area is one of the principal causes contributing to a dense disposition of the incisors, their protrusion, and lack of space for canines. To eliminate this abnormality and achieve stable results, extraction of some permanent teeth is recommended. PMID- 2251710 TI - [The results of using extraoral traction in children with a prognathic bite]. AB - Primary and repeated lateral teleroentgenograms of the head of 37 children aged 4 8 with prognathic occlusion were analyzed, recorded on an average in 2 years after employment of a chin sling with extraoral traction. Analysis has shown normalization of the jaws and occlusion in the sagittal plane, resultant from limitation of mesial transposition of the mandible in the skull in the course of facial skeleton growth. This has been achieved at the expense of inhibition of longitudinal growth of the mandibular body and ascending branches more than twofold as against the reference values and was also a result of mandibular shift due to traction and of enhanced vertical transposition of the mandible in the skull due to distal rotation. The principal indications for the employment of chin sling in the management of prognathic occlusion are intensive growth of the mandible or a tendency to such growth, mesial position of the mandible in the skull, and a combination of these disorders, that may be the principal or additional factors contributing to the pathogenesis of this abnormality. PMID- 2251711 TI - [The prophylactic aspects of dental caries in the antenatal period]. AB - To elucidate the contribution of stress exposures of pregnant women to the development of deciduous teeth caries in their children, the authors have analyzed the stomatological status of 320 infants with favorable and unfavorable antenatal period complicated by stress situations (that were detected with the help of questionnaires) in 3 regions of Moscow, where fluorine levels in potable water are different. The study has revealed that mother's emotional stress in the period of formation of deciduous teeth hard tissues in the fetus reduced infant teeth resistance to caries and lowered the prophylactic effect of fluorine. PMID- 2251712 TI - [The outcomes of chronic parenchymatous parotitis in children]. AB - Time course of the process was examined in 16 patients with chronic parenchymatous parotitis. The follow-up started in children and was proceeded in adults, thus permitting an answer to the problem of parenchymatous parotitis outcome. Dynamic sialographic studies have shown that the process in the gland may develop in three directions, i.e. improvement, deterioration, or stabilization. Positive changes were the most manifest in the initial stage of the disease and not manifest in the late one. The authors' findings help predict the course of parotitis and outcome of the changes in the parotid gland in children. PMID- 2251713 TI - [The conditions for dispensary care with a dentist for naval personnel]. PMID- 2251715 TI - [An analysis of x-rays and the characteristics of interpreting the skialographic picture in the diagnosis of diseases of the teeth and jaws]. PMID- 2251714 TI - [The problems of health education in oral medicine]. PMID- 2251717 TI - [The immune system in the tooth-maxillodental segment area]. PMID- 2251716 TI - [The complications of the tooth extraction operation. I. Alveolitis (its causes, diagnosis, treatment and prevention)]. PMID- 2251719 TI - [Does growth hormone improve quality of life in the elderly?]. PMID- 2251718 TI - [Enamel and dentinal changes in pulpitis and in pulpectomized teeth]. PMID- 2251721 TI - [Extension of life, at what price? Consequences for health care of the elderly]. AB - Prolonging life only makes sense if quality of life is maintained. In biomedical terms this means that life extension should not be accomplished at the cost of an increase of morbidity and dependence. The survival curve must maintain its rectangular shape and compression of morbidity should be sought for. Ageing is not synonymous with disease, and a healthy old age certainly is possible. Many disorders of old age are a result of extrinsic, avoidable factors such as drinking, smoking, eating habits, and inactivity. Prevention must begin in youth. This is the price to be paid by the individual. The medical and scientific community should increase its efforts to develop health care for the aged and increase investments in the study of the ageing process itself. Society as a whole can give support by funding the development of geriatrics and gerontology, and by improving the position and the acceptance of the elderly in daily life. PMID- 2251720 TI - [Extension of life: the apotheosis of the molecular biomedical sciences?]. AB - Evolutionary biologists have shown that many of the adverse effects associated with the ageing process are the (by)products of certain genes: the manifestation of the negative effects of these genes only late in life has effectively constrained their elimination from the germ line by natural selection. In addition, during evolution genes have evolved that govern mechanisms for the protection of the body against exogenous and endogenous insults. These two types of genes, in interaction both with themselves and with the environment specify the maximum life span of a species. New scientific developments, especially in molecular biology, allow the careful analysis of the genetic information and its manipulation. On the basis of these developments more insight will be obtained in the causes of ageing and it will be possible to design new therapies for many of the adverse effects associated with ageing. In the long term it may be possible to remove the basic causes of ageing by genetic manipulation. The mission of the biomedical sciences may then be considered as completed. PMID- 2251722 TI - [Extension of life from a psychogeriatric viewpoint]. AB - Life prolongation (lp) is not only a quantitative, but also a qualitative concept, especially when we look at the factors, which cause life prolongation. One of the consequences of lp is that in the Western world most people live into old age (defined as reaching the age of 65). Now the question is: do we have to continue to work on this product of 'progression-mindedness'. Do we like lp, considering all the negative features which accompany this phenomenon? We think that to a certain extent quality of life has been affected by lp. Qualitative lp we connect to the meaningfulness of lp. What do we understand by meaning? First, we describe some cases. These cases show that meaning is an interactive process, which, we can best conceptualize as commitment. We describe the different categories of commitment and their function. This makes clear the relations between commitment and the development of the individual older person. A consequence would be, that where commitments no longer exist, life prolongation should not be pursued. PMID- 2251723 TI - [2 scenarios on extension of life. Various social consequences of a higher life expectancy]. AB - This article explores the potential consequences of an extra life extension till 2010. For this purpose the method of scenario analysis is used. Life extension is defined as an extra increase in life expectancy at birth (compared to the 'normal' demographic forecast). The optimistic scenario is based on an equal delay of both death and the prevalence of disease and disability. In the pessimistic scenario, only death is delayed, which brings more morbidity. It is stressed that the development of morbidity considerably influences the social consequences of extra life extension, such as the use older people make of the (health) care services system, and the socio-economic and the socio-cultural position of the elderly. In the optimistic scenario the pressure on care services is more or less the same as it would be according to the normal demographic forecast, although the patients/clients are older. Due to the extra increase in life expectancy the costs of social security will be much higher. The percentage of people incapable of work, the age of retirement, the position of the elderly employee in the labour force and the norms and values concerning old age differ in both scenarios. PMID- 2251724 TI - [Longevity and meaning of life. Philosophical-ethical considerations of the theme 'extension of life']. AB - The desire for the extension of life is not one out of many desire in life, but a form of the fundamental desire for life itself. This so called 'categorical desire' is a necessary condition for the many desires in life. The question why we desire for life (and for its extension), is the question for the meaning of life. The searching for a 'natural lifespan' is meaningless when it wants to find in nature a given norm for the duration of life. It can only have meaning when it tries to formulate the conditions for the experience of life as successful and meaningful. A long tradition in philosophy and religion associates the meaning of life with the acknowledgement of its finitude and mortality and with the acceptance of death. As far as the extension of life is motivated by a fear of death and by an effort to escape from it, it is a neglect of what makes life meaningful, and of what makes it (and its extension) worthwhile to desire. PMID- 2251725 TI - [Dental aspects of aging]. AB - The oral cavity fulfils important functions also at an older age in life. In getting older the chances to loose quality in these functions will increase. The following three problem areas are relevant in this respect: teeth can decay by dental caries or by progressive wear; the gums and periodontal tissues may develop serious inflammation and degeneration; finally after extraction of teeth dentures can be provided, but may create new problems in turn. Dental life can be extended by preventive measures and restorative treatment. New developments in the areas of so-called adhesive dentistry and dental implantology may contribute to quality improvement. Based on recently published epidemiological data and on computer simulation studies it is expected that there will be no major changes in need and supply for dental care in the dutch population. However, care spent on children and adults will shift towards care for adults and elderly. PMID- 2251726 TI - Embedded or not? Hydrophobic sequences and membranes. AB - The same translocation machinery appears to be responsible for both the translocation of soluble proteins across membranes and the insertion of integral membrane proteins into the bilayer. A single mechanism is proposed to accommodate these two functions. This model is also extended to explain the paradoxical translocation of mitochondrial and chloroplastic membrane proteins across one or more membranes before they are finally inserted into their target membranes. PMID- 2251727 TI - Histone deletion mutants challenge the molecular clock hypothesis. AB - A basic tenet of the molecular clock hypothesis is that the rate of sequence drift for a protein depends on the number of amino acid residues that are critical for its function. However, recent experiments have determined that, although core histone sequences are highly conserved among eukaryotes, large regions of the proteins are dispensable for growth in yeast. PMID- 2251728 TI - Periplasm underestimated. PMID- 2251729 TI - Tails of RNA polymerase II. AB - Eukaryotic RNA polymerase II contains two distinct structural domains: a catalytic core consisting of subunits that are homologous to other multisubunit RNA polymerases, and a unique extension of the carboxy-terminus of the largest subunit comprising tandem repeats of the seven amino acid sequence YSPTSPS. This repetitive 'tail' domain is essential for polymerase function in vivo. Although the nature of this essential function is unknown, actively transcribing RNA polymerase II is known to be multiphosphorylated on this repetitive domain. PMID- 2251730 TI - The fats of life: the importance and function of protein acylation. AB - Interest in the study of the direct attachment of fatty acids to cellular proteins, termed protein acylation, has been greatly stimulated by recent experimentation that has increased our understanding of the function of the attached lipid. These developments are described, and the possibility that inhibitors of protein acylation might provide new drugs is discussed. PMID- 2251732 TI - Advances in clinical dermatology. PMID- 2251731 TI - Regulation of bacterial physiological processes by three types of protein phosphorylating systems. AB - A single type of protein-phosphorylating system, the ATP-dependent protein kinases, is employed in the regulation of a variety of cellular physiological processes in eukaryotes. By contrast, recent work with bacteria has revealed that three types of protein-phosphorylating systems are involved in regulation: (1) the classical protein kinases, (2) the newly discovered sensor-kinase/response regulator systems, and (3) the multifaceted phosphoenolpyruvate-dependent phosphotransferase system. Physiological and mechanistic aspects of these three evolutionarily distinct systems are discussed. PMID- 2251733 TI - Advances in methodology for diagnosis of allergic skin disease. AB - Advantages of IDST for diagnosis of atopy and selection of antigens for hyposensitization include the following: 1. The test is widely accepted by clients. 2. The clinician can select individual test allergens based on the patient history and geographic location. 3. It has been the standard for diagnosing atopy in the dog for more than 40 years. Disadvantages of IDST include the following: 1. The test should be performed on a regular basis to maintain reliability. 2. Interpretation of test results is subjective. 3. The test is not standardized on the basis of the examiner, source of the allergen, or reproducibility. 4. There is occasional difficulty in performing the test (e.g., need for sedation). 5. Anaphylaxis is a potential risk. 6. A significant amount of office time is needed to perform the test. 7. Condition of the patient's skin (e.g., lichenification, hyperpigmentation, pyoderma) may preclude its use. 8. There is a possibility of failure to test for appropriate allergens. 9. There may be false-positive and false-negative reactions. 10. Other medications can interfere with the test (e.g., antihistamines, corticosteroids). Advantages of in vitro testing for diagnosis of atopy and selecting antigens for hyposensitization include the following.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251735 TI - Allergic contact dermatitis in the dog. Principles and diagnosis. AB - Allergic contact dermatitis is a rare hypersensitivity disorder in the dog. Clinical diagnosis is not easy. Primary lesions are transient. Secondary lesions caused by chronic inflammation and self-trauma are commonly present on typical areas, especially in sparsely haired regions and on the feet. A presumptive diagnosis can be made based on the history, clinical signs, and positive standardized closed patch testing. Histopathology and basophil degranulation testing may also be helpful in supporting the diagnosis and in identifying the offending allergens. However, a definitive diagnosis can be made only after restriction-provocation testing. With better understanding of the pathogenesis and clinical signs, and with increased availability of diagnostic tests (especially a standardized closed patch test), increased recognition of this dermatosis is expected. PMID- 2251734 TI - Current diagnostic techniques for evaluating thyroid function in the dog. AB - Hypothyroidism is a common endocrinopathy in dogs. There are a wide variety of diagnostic tests to evaluate thyroid function. The measurement of basal thyroid hormone concentrations is used widely as an indicator of thyroid function; however, there are many factors that may affect basal hormone concentrations. The thyrotropic stimulation test is not affected by many of these factors, and often it is preferred for this reason. Current diagnostic procedures for evaluating thyroid function for the veterinary practitioner are reviewed. PMID- 2251736 TI - Management of dermatophyte infections in catteries and multiple-cat households. AB - Successful elimination of dermatophytosis from cats requires clipping of the haircoat, weekly or twice-weekly antifungal dips, and systemic antifungal therapy. In addition, the environment should be repeatedly decontaminated with an appropriate chemical, for example, household bleach. Successful treatment may take weeks to months depending on the circumstances. Monitoring response to therapy is best done via toothbrush-culturing techniques and inoculation of the bristles onto fungal culture media. Currently, there is no successful fungal vaccine, and prevention of reinfection can be difficult and requires careful quarantine measures. PMID- 2251737 TI - Fatty acid supplementation and skin disease. AB - The importance of dietary fatty acids to the health of the skin was recognized more than 60 years ago. Fatty acids are important in providing membrane fluidity and maintaining the cutaneous water permeability barrier. Fatty acids function as precursors of eicosanoids. Eicosanoids, which include prostaglandins and leukotrienes, influence cellular interactions, cellular proliferation, and inflammation. Certain diseases, such as atopy and hypothyroidism, are characterized by abnormalities in fatty acid metabolism. Dietary manipulations may be useful in the treatment of diseases mediated by eicosanoids. PMID- 2251738 TI - Long-term management of atopic disease in the dog. AB - Canine atopy is a common dermatologic disorder. Because the disease most frequently strikes young dogs, lifetime management strategies are necessary. Consideration must be given to the treatment of pruritus and secondary manifestations of the allergy, such as pyoderma, otitis externa, and seborrhea, to manage these patients successfully. The use of glucocorticoid therapy and hyposensitization are discussed. PMID- 2251739 TI - Strategies for management of recurrent pyoderma in dogs. AB - Staphylococcal skin infection (pyoderma) is a common clinical problem in dogs. The infection can be either superficial or deep. Most cases of staphylococcal pyoderma occur secondary to a definable underlying cause. Treatment consists of finding the underlying cause and correcting it, if possible, and treating the pyoderma with antibiotics. Antibacterial shampoos may be used as adjunct treatment, but corticosteroid drugs should not be used. When canine pyoderma recurs in the absence of an identifiable underlying cause, several treatment strategies can be effective in eliminating recurrence or limiting its severity. Frequent antibacterial shampoos are an easy and sometimes effective method. Immunomodulatory drugs are variably effective. Some commercially available bacterins are clearly helpful in treating recurrent pyoderma. As a last resort, the clinician may opt to keep the patient on long-term antibiotic therapy. Such therapy may promote development and dissemination of resistant strains of Staphylococcus and should be used only if absolutely necessary. PMID- 2251740 TI - Synthetic retinoids in veterinary dermatology. AB - The synthetic retinoids, isotretinoin (Accutane) and etretinate (Tegison) are vitamin A analogs. They affect epithelial differentiation and thus have potential for therapy for disorders of epithelial maturation such as keratinization defects of cutaneous neoplasia. The pharmacology, indications for use, clinical experience, potential toxicities, and recommended monitoring of these drugs are discussed. PMID- 2251741 TI - Sex hormone-related and growth hormone-related alopecias. AB - Canine endocrine dermatoses are characterized by bilateral symmetrical alopecia. Although growth hormone-related and sex hormone-related dermatoses are less common than hypothyroidism and hyperadrenocorticism, they are important causes of hormonal skin disease. Several new syndromes associated with growth and sex hormones recently have been described. PMID- 2251742 TI - Newly reported skin disease syndromes in the dog. AB - Several recently recognized canine dermatoses are described. Syndromes discussed include superficial necrolytic dermatitis, Malasezzia dermatitis, sebaceous adenitis, nodular dermatofibrosis in German shepherd dogs, solar-induced dermatitis, and acrodermatitis. PMID- 2251743 TI - Recently described feline dermatoses. AB - This article discusses the etiology, clinical signs, diagnosis, and treatment of several diseases. Feline immunodeficiency, virus infection, cryptococcosis, dermatophyte pseudomycetomas, demodicosis, Sezary-like syndrome, and discoid lupus erythematosus in cats are reviewed. PMID- 2251744 TI - Skin diseases of the Chinese Shar-Pei. AB - This article deals with the unique skin disorders seen only in the Shar-Pei. The difference between skin diseases in Shar-Pei and other breeds is described. Prevention and treatment are discussed. Suggestions are given to alter the breed's anatomy slightly to decrease the genetic predisposition to certain dermatoses. PMID- 2251745 TI - The egg production of Toxocara vitulorum in Asian buffalo (Bubalus bubalis). AB - The egg production of Toxocara vitulorum in Asian buffalo has been studied. Eggs were first present in the faeces of calves when they were 22.3 +/- 1.6 days old. In calves treated with pyrantel when 3 days old, the age at first patency was extended by 3.5 days indicating that there was no pre-natal transmission. Calves on only half the milk of the cow had a significantly longer prepatent period of 27.7 +/- 2.2 days. The peak egg output occurred in calves 35.7 +/- 2.6 days old and had a duration of 5.5 +/- 2.5 days with 98,000 +/- 63,700 eggs g-1 of faeces. The duration of the patent period was 35 +/- 12 days. The average lengths of populations of mature female parasites from different hosts at the time of peak egg output or older, ranged from 15.0 to 31.0 cm and was correlated with those of the males in the same populations (10.6-20.4 cm). The size of females was not affected by intraspecific competition. The proportion of males in the populations was 0.39 +/- 0.11. The egg output per female per day at the peak was 110,000 +/- 58,000 and was correlated with the size of the females at autopsy, but the egg output per female per day at the time of autopsy was lower and was not correlated, so it was concluded that the drop in egg counts was the result of reduced fecundity. The fertility of the eggs from faeces was greater than 92% throughout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251746 TI - Effects of tactical late-season treatments with ivermectin on calves naturally exposed to trichostrongyles. AB - This study was conducted to evaluate the effects of tactical treatments with ivermectin against trichostrongyles in first-season grazing heifer calves in the Danish marshland. A group of Black-Pied Friesian calves was turned out in early May on a permanent pasture naturally infected with trichostrongyle larvae. In late July, when high herbage infectivity started to appear, the pasture was divided into two plots of equal size, which from then and until housing in late October were each grazed by half of the original group of calves. One of these groups was given three anthelmintic treatments with ivermectin at 4-week intervals starting in late July. The other group served as non-treated controls. Ostertagia ostertagi and Cooperia oncophora were the predominant trichostrongyles. Nematodirus helvetianus was observed on few occasions. Although the animals were exposed to a high herbage infectivity from July onwards, the anthelmintic treatments conferred a significant reduction in trichostrongyle loads, as evidenced by an almost complete cessation of egg excretion and a significant lowering of pepsinogen and gastrin levels in the blood. This was reflected in higher weight gains. PMID- 2251747 TI - A modified technique for the estimation of the number of infective nematode larvae present on pasture, and its application in the field under South Australian conditions. AB - A modified technique for the recovery of larvae from pasture is described involving two centrifugations of pasture washings in a solution of potassium iodide. On average, the technique recovered 96% of larvae and was simple to perform. At three sites in South Australia (rainfall 550-330 mm year-1), the numbers of larvae present on pasture each month using this technique was compared with results obtained using one or four tracer sheep. The general pattern of larval availability was similar using the two methods, but discrepancies were noted. In some instances, particularly when numbers of larvae were low, pasture sampling underestimated the numbers of larvae available to sheep; in other situations, when the numbers of larvae were high, tracer sheep probably underestimated the number being ingested. Increasing the numbers of tracer sheep from one to four did not appreciably increase the correspondence between the two methods. PMID- 2251748 TI - Evaluation of an enzyme-linked immunosorbent assay to detect specific antibodies in pigs infested with the tick Ornithodoros erraticus (Argasidae). AB - Ornithodoros erraticus is known to transmit the virus that causes the highly contagious disease, African Swine Fever, in Spain. As part of the disease eradication campaign, an ELISA test to detect specific antibodies against the tick was developed. The ELISA, using salivary gland preparations as an antigen, showed high sensitivity and was able to detect as few as 10 adult ticks. The specific antibodies were detected in the sera 6 weeks after the primary infestation and strongly increased after the challenge. The utility of this test under field conditions was also tested. PMID- 2251749 TI - Larvicidal activity of blastospores and conidiospores of Beauveria bassiana (strain GK 2016) against age groups of Aedes aegypti. AB - Laboratory bioassays of two development stages, blastospores (BS) and conidiospores (CS) of Beauveria bassiana (strain GK 2016) against Aedes aegypti larvae were conducted at 27 degrees C. In Study 1, against 24 h post-hatched larvae, both BS and CS stages showed significant difference in their respective larvicidal efficacy over the control (P less than 0.0001). Larval mortality between 24 and 96 h post-exposure was significantly higher than any other time period investigated. Significantly higher larval mortality was observed with BS or CS at 10(8) ml-1 over lower concentrations (P less than 0.05). In Study 2, against different age groups, 12-24 h post-hatched larvae showed significantly higher mortality when treated with BS or CS than older age groups (P less than 0.05). A significant difference was found in the larvicidal potency of B. bassiana at different fungal stages. PMID- 2251750 TI - Prevalence and serology of hydatidosis in large ruminants of Pakistan. AB - Hydatidosis was seen in 38.90% of cattle, 33.06% of buffaloes and 58.9% of camels slaughtered at a local abattoir. No statistically significant seasonal difference in prevalence was observed. Most cysts (63.14%) were infertile. Protein and carbohydrate contents of fluid from fertile and infertile cysts did not differ significantly. Sensitivity, specificity and efficiency of indirect haemagglutination test and enzyme-linked immunosorbent assay were low. PMID- 2251751 TI - Studies on the stage of action of lasalocid against Eimeria tenella and Eimeria acervulina in the chicken. AB - Broiler chickens in battery pens were either fed a diet containing 100 ppm lasalocid or no drug for 24 h prior to inoculation with sporulated oocysts of Eimeria tenella or Eimeria acervulina. Different groups of birds remained on medicated feed for 24, 48, 72, 96, 120 or 144 h after inoculation. Conversely, other groups started on an unmedicated diet, were given medicated feed at different times after oocyst inoculation. Starting lasalocid medication 24 h (E. tenella) or 48 h (E. acervulina) after inoculation reduced the lesions and improved the weight gain. There was no significant difference in performance of birds after withdrawal of the drug at 48 h (E. tenella) or 72 h (E. acervulina) and thereafter. Starting lasalocid medication at 96 or 120 h did not suppress but rather reduced oocyst production. PMID- 2251752 TI - [Soviet roentgenology in the years of World War II]. PMID- 2251753 TI - [Current methods of radiotherapy of malignant tumors and prospects for their development]. PMID- 2251755 TI - [The current status and future of the development of maxillofacial radiography]. PMID- 2251754 TI - [The state of the coronary arteries during balloon dilatation following thrombolytic therapy of acute myocardial infarction (a quantitative angiographic study)]. AB - The paper is concerned with the investigation of 52 patients who received i.v. thrombolytic therapy and "delayed" balloon dilatation of the coronary arteries in the first hours of acute myocardial infarction for the first 6 days. The investigation was repeated 6 mos after the onset of disease. Analysis of the coronaroventriculography results has shown that a combined use of i.v. thrombolytic therapy and delayed balloon dilatation of the coronary arteries results in a considerable and prolonged improvement of vascular permeability attended by a significant improvement of left ventricular local function and a decrease in the number of reocclusions. Infarction-related artery restenosis after combined therapy has little influence on left ventricular function which can be probably associated with a slow rate of its formation. Infarction-related vascular reocclusion leads to marked impairment of left ventricular total and local function. PMID- 2251756 TI - [The roentgenologic service in the era of perestroika]. PMID- 2251757 TI - [Computed tomography in the comprehensive diagnosis of acute diseases and injuries]. AB - The author presents the results of a CT use during combined investigation on 2500 patients and the wounded who were admitted to hospital on emergency as well as patients who developed serious complications during treatment, especially in the postoperative period. CT findings were verified during operation, at autopsy or during a follow-up. They were indicative of a high effectiveness of emergency CT of different organs and systems in the diagnosis of lesions, acute diseases and their complications. The use of CT permitted considerable reduction of a diagnostic (preoperative) period, a decrease in use of routine invasive x-ray and surgical methods, and the improvement of therapeutic results. PMID- 2251758 TI - [The x-ray morphological characteristics of the early manifestations of sarcoidosis]. AB - The paper is devoted to an analysis of combined x-ray findings supplemented by CT findings in patients with sarcoidosis detected for the first time with early signs of this disease. A conclusion has been made that apart from lymph node enlargement, sarcoidosis is characterized by lung parenchymal changes which manifest themselves as symptoms of broncho-alveolitis. Characteristic x-ray symptom complexes are described. Roentgeno-semiotics of these changes were compared with the results of morphological investigation of transbronchial puncture specimens. Roentgenologically detectable changes showed good correlation with morphology findings. The authors have also emphasized the importance of morphological verification of this disease at early stages. PMID- 2251759 TI - [The seventieth anniversary of Vestnik Rentgenologii i Radiologii]. PMID- 2251760 TI - [Computed tomography in the diagnosis of endophytic cancer of the stomach]. AB - The authors discuss the potentialities of CT in the diagnosis of endophytic stomach cancer. They proposed a method for CT of the stomach based on a pneumatic study of its lumen via a nasogastric probe with graded inflation and repeated CT imaging. The major CT-semiotics of endophytic stomach cancer were obtained. This method should be employed in combination with the existing routine methods of stomach cancer diagnosis, and its efficacy is in direct relation to the quality of preliminary routine x-ray and endoscopic investigations. PMID- 2251761 TI - [The comprehensive diagnosis of changes in the stomach and small intestine in patients with chronic colitis]. AB - Combined investigation of 121 patients with chronic colitis (CC) has shown chronic gastroduodenitis in 90.9% and the intestinal malabsorption syndrome in all the patients. Comparison of the frequency of intestinal malabsorption symptoms has shown that they are less marked in CC than in chronic enterocolitis with predominant intestinal lesion. PMID- 2251762 TI - [Irreversible loss of the substantia compacta in metabolic bone diseases based on roentgenogrammetric data]. AB - A study was made of gram roentgenographic indices of the compact substance (CS) in metabolic skeletal diseases: of the cortical layer summary thickness (CST) and a cortical area (CA) of the metacarpal bone II in 310 patients and the femoral cortical index (FCI) in 184 patients. Three components in CS loss were singled out: involution, metabolic and inert. Irreversibility of endocortical loss of the osseous tissue was shown and interpreted as fast developing involution osteoporosis. CST is a more sensitive index of CS loss than FCI though the combination of both indices provides more information on CS loss. PMID- 2251763 TI - [Computed tomographic semiotics of chronic subdural hematomas]. AB - Analysis of the results of investigation of 72 patients with verified chronic subdural hematomas (CSH) has revealed their CT dense characteristics, the peculiarities of their structure compared with the time of their formation, the patients' age, the clinical stage of disease, and operative findings. Direct and indirect CT signs of uni- and bilateral hemispherical chronic subdural hematomas were described. PMID- 2251764 TI - Selective alteration of bovine neutrophil responses by recombinant bovine interleukin-1 beta. AB - The effects of recombinant bovine interleukin-1 beta (rBIL-1 beta) upon in vitro bovine neutrophil functions were determined. Exposure of peripheral blood neutrophils to various concentrations of rBIL-1 beta induced dose dependent suppression of the phagocyte's ability to migrate under agarose. Preincubation of neutrophils with rBIL-1 beta did not influence their ability to ingest radiolabelled Staphylococcus aureus nor did it induce hydrogen peroxide production or elastase release. However, pretreatment of phagocytes with rBIL-1 beta did result in a dose-dependent enhancement of opsonized zymosan-induced H2O2 production. In contrast, rBIL-1 beta had no effect upon the ability of opsonized zymosan-stimulated neutrophils to release elastase from primary granules. Pretreatment of neutrophils with rBIL-1 beta for as little as 15 min was sufficient to induce suppression of migration and enhancement of opsonized zymosan-induced H2O2 production. These results suggest rBIL-1 beta is capable of directly modulating selected neutrophil activities. In addition, rBIL-1 beta appears to augment the phagocyte's oxidative metabolic responses to subsequent stimulation by microbial antigens. PMID- 2251765 TI - A novel population of cells in the peripheral blood of a cow with a neurofibrosarcoma. AB - An unusual population of leukocytes was observed in the peripheral blood of a cow with a large tumor burden, using flow microfluorimetry. This new population accounted for 50% of the total cells in the peripheral blood of this animal. These cells expressed the p150,95 molecule (bovine CD11c equivalent), identified by the monoclonal antibody C5B6, a molecule found on myeloid cells and activated lymphocytes. The new population did not express the pan T molecules BoCD2 (the bovine T11 equivalent), BoCD5 (the bovine CD5 equivalent) or surface IgM. Isolated peripheral blood mononuclear cells maintained in bulk culture were able to kill autologous tumor cells and BHV-1 infected A549 in an NK-like assay. In vitro cytotoxicity by cells cultured from the peripheral blood of this animal was augmented 2- to 4-fold by the addition of IL-2. PMID- 2251766 TI - Role of the chancre in induction of immunity to tsetse-transmitted Trypanosoma (Nannomonas) congolense in goats. AB - Local skin reactions (chancres) developed in goats at the sites of deposition, by tsetse flies, of metacyclics of Trypanosoma congolense. The chancres developed much faster and were more pronounced when ten infected tsetse were allowed to feed on a spot as compared to only one fly per spot. The initial host cellular reaction in the chancre was predominantly polymorphonuclear, followed at the peak of development of the chancre by a predominantly lymphoblastic and plasmacytic reaction. Trypanosomes were found in various stages of division as well as degeneration in chancre biopsies taken at various days post-infection (p.i.). Most of the trypanosomes recovered from the chancre tissue fluid were found to bear the same variable surface glycoprotein (VSG) epitopes as the corresponding metacyclics for as long as 13 days p.i., as revealed by indirect immunofluorescence using mouse anti-metacyclic VSG hyperimmune sera and monoclonal antibodies. Immunization of goats with metacyclic trypanosomes, by exposure to infected tsetse bites followed by treatment of the infected goats on day 13 p.i., gave rise to the development of protection to homologous tsetse transmitted challenge, whilst immunization by intravenous inoculation of the metacyclics did not induce such protection. Chancre formation would thus appear to be vital for the induction of comprehensive immune recognition of the metacyclic variable antigen repertoire deposited in the skin by infected tsetse, and hence development of protective immunity. PMID- 2251767 TI - Inhibitory effect of African swine fever virus on lectin-dependent swine lymphocyte proliferation. AB - The incubation of swine peripheral blood mononuclear cells (PBMC) with African swine fever (ASF) virus preparations strongly inhibited the proliferative response of lymphocytes to PHA and other lectins. The inhibition, which persisted after inactivation of the virus by UV radiation, was dependent upon the dose and the time that virus preparations were present in cultures. When virus preparations were fractionated by ultracentrifugation, the inhibitory activity resulted to be soluble, whereas no activity was found in the sedimented viral fraction. However, the preincubation during 4 days of this sedimented fraction with swine PBMC, before the addition of the mitogen, restored the inhibitory activity. The results obtained suggest that the inhibition is mediated by one or more soluble factors released by swine PBMC after coincubation with ASF virus in a time dependent process. These factors show a molecular weight between 40 and 80 kDa by gel filtration chromatography. The inhibitory activity described in the present paper is an indication of inhibition of lymphocyte function produced by ASF virus which can help to understand how this virus escapes from the host immune system. PMID- 2251768 TI - Characterization of monoclonal antibodies to channel catfish, Ictalurus punctatus, leucocytes. AB - Four monoclonal antibodies (MAbs) were evaluated for specific reactions to various catfish peripheral blood leucocytes and anterior kidney cells. The MAb 9E1 served as a standard and positive control for all test reactions because of its defined reactivity with channel catfish immunoglobulin and immunoglobulin bearing cells. Of the four MAbs, two have been characterized as being specific for a non-immunoglobulin marker on lymphocytes, thus marking T lymphocytes and two were specific for catfish neutrophils. Morphological, flow cytometric and functional analysis of the reactive cells verified these findings. PMID- 2251769 TI - [Does early echocardiography contribute to the prediction of complications in acute myocardial infarct?]. AB - The authors give an account of their experience with early echocardiography (two dimensional examination, division of left ventricle into 20 segments) during stratification of patients with acute myocardial infarction (a group of patients with a first infarction). They evaluated the presence or absence of serious asynergy (akinesia or dyskinesia) of the left ventricle and its relationship to the incidence of complications (serious dysrhythmia, decompensation, cardiogenic shock and death). The relations between asynergy and different complications were tested by means of multidimensional contingency tables. A statistically significant partial correlation (p less than 0.01) was recorded between the most serious asynergy and the presence of decompensation and also cardiogenic shock. The detection of serious asynergy of the left ventricle is a useful stratification indicator of the risk of the acute infarction, as no patient without asynergy died or overcame cardiogenic shock. PMID- 2251770 TI - [Paroxysmal atrioventricular block]. AB - The authors analyzed paroxysmal atrioventricular blocks which were not frequency dependent. It was a clinical, electrocardiographic and electrophysiological evaluation. The authors draw attention to the pitfalls of diagnosis and emphasize that the problem of interpretation of atrioventricular (intraventricular) conductivity is unequivocally associated with the problem of indication of permanent cardiac pacing. Based on their own experience, the authors describe the procedure used for establishment of the diagnosis of paroxysms of atrioventricular blocks. What are the main conclusions? 1. In the first place it is necessary to pay attention to the history of syncopes. 2. On the conventional ECG we find usually disorders of atrioventricular and intraventricular conductivity. 3. Electrophysiological examination should be always supplemented also by pharmacological intervention, using Gilurytmal by the i.v. route. PMID- 2251771 TI - [Plasma renin activity and aldosterone in patients with essential hypertension]. AB - The authors examined the plasma renin activity (PRA) in 80 patients and plasma aldosterone (PA) in 27 patients with essential hypertension (EH). They confirmed the significant drop of stimulated PRA with age. The PA levels of hypertonic patients did not change with age and did not change significantly in relation to PRA. In obese hypertonic patients a satisfactory response of PRA to stimulation was lacking, while PA reacted adequately. The PA levels are thus in older age groups as well as in obese subjects much higher, as compared with relatively low PRA levels. In relation to the stage of EH the authors did not find any significant differences of PRA levels. PMID- 2251772 TI - [Cholecystolithiasis in type II diabetics]. AB - In a group of 166 type II diabetics hospitalized in a medical department the authors made clinical and ultrasonographic examinations focused on the presence of cholecystolithiasis. The control group was formed by 67 subjects with normal glucose tolerance. None of the patients were hospitalized on account of biliary disease. The purpose of the work was to 1. evaluate the difference in the incidence of cholecystolithiasis in diabetic patients and controls with regard to age and sex, 2. to assess differences in the incidence of obesity, impaired lipid metabolism and a positive biliary family--history in diabetics and controls with lithiasis, 3. to evaluate diabetes and the presence of microalbuminuria. In the authors' group cholecystolithiasis is significantly more frequent in diabetics as compared with controls, in men, women and people above 65 years (p less than 0.01). The group of diabetics and controls with lithiasis does not differ as to the incidence of obesity, hyperlipoproteinaemia and positive family-history of biliary disease. No significant differences in parameters of compensation of diabetes nor differences in the incidence of microalbuminuria were found between diabetics with and without lithiasis. The results suggest that it is useful to screen cholecystolithiasis in diabetic subjects. PMID- 2251773 TI - [Weight reduction in obese patients in the early period after myocardial infarct]. AB - During the early rehabilitation stage to 27 obese subjects after a non complicated myocardial infarction a low energy diet was administered (2 and 5 MJ resp.--19 patients) or diet no. 7 or 9 (9 and 6 MJ--8 patients). The regime was started on average 8.4 days (at least 5 days) after the acute attack, its tolerance was satisfactory, there were no complications. In the group with a markedly low energy diet the cholesterol and total lipid levels declined. The body weight declined in both groups. It was revealed that early body weight reduction in obese subjects with non-complicated myocardial infarction involves no risk and the hospitalization period can be effectively used also as introduction to the regime in secondary prevention of ischaemic heart disease. PMID- 2251774 TI - [The HLA crossmatching test before thrombocyte transfusion. Comparison of 3 methods]. AB - Weak accessory HLA antibodies in HLA sera were assessed by three test--the microlymphocytotoxic, antiglobulin cytotoxic and fluorescent cytotoxic test. Most frequently they were detected by the antiglobulin cytotoxic test (69.64%), followed by the fluorescent cytotoxic test (55.73%) and least frequently by the microlymphocytotoxic test (45.77%). From the results ensues that the antiglobulin cytotoxic test is a suitable method of crossmatch before thrombocyte transfusions to patients who developed reactions after transfusions or where therapy failed although the crossmatch was performed by the microlymphocytotoxic test between the donor's lymphocytes and the patient's serum and the test was negative. PMID- 2251775 TI - [Ebstein's anomaly of the tricuspid valve in adulthood]. AB - Ebstein's anomaly is a rare congenital malformation of the heart, the basic feature of which is dislocation of the tricuspid valve into the right ventricular cavity. The frequently present dysplasia of the tricuspid valve is considered as integral part of this anomaly. Although affected subjects may reach adult age, it is no exception that the diagnosis of this anomaly in clinical practice is problematical, as apparent from the presented case-history. The authors emphasize the importance of two-dimensional echocardiography which provides very valuable morphological information needed not only for establishment of the diagnosis of this malformation but it makes it also possible to foresee the prognosis of the patient and the therapeutic tactics--conservative or surgical treatment. PMID- 2251776 TI - [Thrombotic thrombocytopenic purpura. Report of 2 cases]. AB - The authors present a report on thrombotic thrombocytopenic purpura in a 63-year old woman and a 23-year-old man. In both the disease was diagnosed in vivo. In the first case the patient died in the fulminant stage, in the second case, treated for three weeks, death occurred after an infectious complication. In the first case necropsy confirmed the florid stage of the disease, in the second case only late non-specific changes were detected. The varied and prolonged history of the second case can be explained by repeated attacks of the disease, the last one being fatal. PMID- 2251777 TI - [New quinolines for the treatment of urinary tract infections]. AB - The submitted review draws attention to the role of new quinolones in anti infectious chemotherapy of the urinary pathways. It gives an account of published results of treatment and prophylaxis of infections of the urinary pathways and the prostate, as compared with hitherto used chemotherapeutic drugs and antibiotics. PMID- 2251778 TI - [Reactive oxygen metabolites, antioxidant activity, antioxidants and aging]. AB - The authors refer to literary data on the much discussed issues of reactive oxygen metabolites, presumably involved in a variety of physiological and pathophysiological processes as well as in ageing. The other part of the paper deals with intra- and extracellular antioxidant mechanisms and the feasibility of using different antioxidants to constrain the deleterious effects produced by reactive oxygen products in pathological processes which accelerate ageing. The authors' own observations are also presented. PMID- 2251779 TI - [Myths and superstitions in the treatment of pain]. AB - Based on recent pharmacological and pathophysiological findings, the authors confront still persisting unsubstantiated views with modern ones regarding the duration of action of analgetics, equianalgesic doses, abstention symptoms, development of dependence, tolerance and the use of co-analgetics. An important place in the potentiation of the effect of analgetics is held by the application of suitable procedures and methods in the sphere of nursing care. PMID- 2251780 TI - [Compulsory medical confidentiality in association with AIDS]. AB - The author deals with the problem of medical secrecy in conjunction with AIDS. He draws attention to some problems pertaining to the relationship of legal authorities and health facilities in conjunction with the provision of data from the medical documentation. He presents brief information on the discussion about compulsory medical secrecy in some western countries in conjunction with AIDS. The author reaches the conclusion that it will be necessary to create prerequisite conditions for the objective evaluation of the problem, while accepting the justified protection of rights of HIV carriers and patients with AIDS, as well as the interests of preserving the health of other citizens. PMID- 2251781 TI - [Use of nonparametric methods in medicine. IV. Comparison of levels in more than 2 samples]. AB - The authors mention two tests for comparison of the level of random variables in more than two random samples. It is thus a question of generalization of methods presented in parts II and III. Friedman's test resolves the position for dependent samples when data assembled during different experimental situations in the same group are to be evaluated. This test calls for a complete series of measurements from every statistical unit, in mathematical terminology this means that the samples are equally extensive. In case of large samples Friedman's test is based on chi 2 distribution; for a small number of samples special tables of critical values are given. Kruskal-Wallis's test resolves the position for independent samples. It is also based on chi 2 distribution. PMID- 2251782 TI - [Treatment of hyperglycemic coma states in diabetics]. PMID- 2251783 TI - [Changes in the immunochemical properties of beta-lactoglobulin during proteolysis and exposure to various physico-chemical factors]. AB - Heating of cow milk beta-lactoglobulin at 96 degrees, pH 8.0 led to the protein aggregation because of intermolecular disulfide exchange as shown by agarose gel immunoelectrophoresis, where additional precipitation strips were detected. At the same time, there was not observed dissociation of beta-lactoglobulin into separate fractions after proteolysis or denaturation in 8 M urea. beta Lactoglobulin, its thermoaggregated and S-carboxymethyl denaturated forms exhibited similar anaphylactic effect on sensitized guinea pigs. Allergenic properties of beta-lactoglobulin appears to be unaltered in food hydrolyzates after thermal treatment and limited proteolysis. PMID- 2251784 TI - [The effect of ethanol and the catalase inhibitor 3-amino-1,2,4-triazole on lipid peroxidation in rat liver homogenate and subcellular fractions]. AB - Effects of repeated administration of ethanol and the catalase inhibitor 3-amino 1,2,4-triazole on the rate of Fe2+/ADP-ascorbate induced (nonenzymatic) lipid peroxidation were studied in rat liver tissue homogenate and subcellular fractions using estimation of low-level chemiluminescence and malonic dialdehyde content. The rate of lipid peroxidation was decreased in whole and nuclear-free homogenates as a result of combined or individual ethanol and aminotriazole treatment. However, this pattern was unaltered in mitochondrial and microsomal fractions. Both these agents did not affect the content of conjugated dienes in lipid containing extracts of subcellular fractions as well as the total malonic dialdehyde concentration in whole liver tissue homogenate. The data obtained suggest that antioxidative protein factor, inhibiting nonenzymatic lipid peroxidation in biological membranes, was induced in liver cytosol of rats repeatedly administered with ethanol and/or amino-triazole. PMID- 2251785 TI - [Active metabolites of vitamin D as regulators of proliferation and differentiation of monocyte-macrophage cells (review)]. PMID- 2251786 TI - [Antioxidative properties of glycyrrhyzic acid salts and their effect on the liver monooxygenase system]. AB - Antioxidative activity of potassium- and sodium glycyrrhizins was detected by means of chemoluminescence procedure. As shown by the spectral studies the glycyrrhizin salts formed complex of the I type with cytochrome P-450 from rat liver microsomes, inhibited inactivation of isolated cytochrome P-450LM2 and induced hemoprotein formation after administration into rats. The preparations of glycyrrhizic acid appear to be useful for treatment of toxic impairment of liver tissue. PMID- 2251787 TI - [Multiple forms of monoaminoxidase in the rat brain during experimental catatonia]. AB - Catalytic properties of multiple forms (separated by affinity chromatography) of rats brain mitochondrial monoamine oxidase (MAO, MAO-I, MAO-11 alpha, MAO-11 beta, MAO-111) have been studied in the animals selected for propensity to development of catatonic syndrome considered as an experimental model of the catatonic syndrome occurring in schizophrenia. It was shown that in experimental catatonia (as compared with rats of the corresponding control group) there was a dramatic increase in the brain stem of the rate of oxidative deamination of beta phenylethylamine catalyzed by MAO-III; there was also a statistically significant (albeit less expressed than in the experiments with beta-phenylethylamine) increase in the rate of deamination of tyramine and a decrease in the rate of deamination of serotonin. In the systems with MAO-II beta we detected statistically significant increase in the rates of deamination of tyramine and beta-phenylethylamine in experimental catatonia as compared with corresponding control. Studies of multiple forms of brain MAO provide more informative data than estimation of "total" MAO activity (without separation of the multiple forms of this enzyme). PMID- 2251788 TI - [The use of highly sensitive immunoblotting for detecting the phenylalanine hydroxylase antigen in human platelets]. AB - Incubation of nitrocellulose filters containing proteins in solutions of organic alcohols (ethanol, methanol, isopropanol) enabled to increase the immunoblotting sensitivity after denaturating electrophoresis in presence of SDS. Maximal elevation of the label sensitivity (4-6-fold) was observed after incubation of these filters in 30% isopropanol within 2 hrs. The effect of sensitivity elevation appears to be caused by the antigen renaturation due to SDS washing off. The modified procedure of immunoblotting allowed to detect phenylalanine hydroxylase antigen in human thrombocytes. The antigen had electrophoretic mobility similar to that of phenylalanine hydroxylase from liver tissue; its concentration constituted less than 0.1 microgram per 1 mg of protein in thrombocytes. PMID- 2251789 TI - [Protective effect of selenium in acute T-2 mycotoxicosis]. AB - Male Wistar rats were fed diets supplemented with selenium (0.5 and 2.5 mg/kg) for 6 weeks. When T-2 toxin was administered at 3.8 mg/kg body weight; sings of intoxication were less distinct in rats fed selenium-supplemented diets. Mortality caused by T-2 toxin was two times lower if selenium content amounted to 2.5 mg/kg. The level of cytochrome P-450 and the rate of deethylation of 7 ethoxycoumarin were considerably decreased in the liver of rats that received T-2 toxin and fed a diet with high selenium content. At the same time the activity of epoxide hydrolase and UDP-glucuronosyltransferase was significantly higher (1.6 and 1.7 times more) as compared with unsupplemented group. The results obtained allow to assume that there is a relationship between the decrease of T-2 toxin toxicity and the change in its metabolism in rats fed selenium-supplemented diets. PMID- 2251790 TI - [Hetero-oligoproteins containing pancreatic ribonuclease--enzyme conjugates of prolonged action]. AB - Conjugates containing blood serum albumin and pancreatic ribonuclease, produced by means of polycondensation reaction, exhibited higher half-life in rabbit circulation as compared with non-modified enzyme. Presence of the protein-carrier contributed to elevation of the ribonuclease therapeutic efficiency and enabled to decrease the quantity of injections. PMID- 2251791 TI - [Contribution of lysosomal enzymes into degradation of short- and long-lived proteins in human embryonal fibroblasts with abnormal chromosome complement]. AB - Degradation of short- and long-life proteins was studied in human embryonal fibroblasts with normal karyotype, trisomy and triploidy. Degradation of both short- and long-life proteins by means of lysosomal enzymes was elevated in fibroblasts with anomalous karyotype at the logarithmic phase of growth as compared with normal state, when lysosomotropic agent NH4Cl was used. In transition to stationary phase of growth participation of the lysosomal system in degradation of long-life proteins was increased in fibroblasts with normal karyotype, whereas degradation of these proteins in aneuploid fibroblasts maintained at the level found during the logarithmic phase of growth. Lysosomal enzymes did not participate apparently in degradation of short-life proteins in fibroblasts with normal and anomalous karyotype at both phases of growth. The data obtained suggest that chromosomal disbalance was related to impaired regulation of protein degradation as well as to possible alteration in the ratio of cytosol and lysosomal proteolysis. PMID- 2251792 TI - [Fractionation of proteins of chorionic villi and chorionic membranes by two dimensional electrophoresis]. AB - Human chorionic villi and choriomembrane proteins were analyzed by two dimensional electrophoresis. The samples were obtained during the first trimester of pregnancy and were solubilized in buffer containing Triton X-100 and CHAPS. High molecular weight proteins with Mr above 200 KDa and proteins with basic pI were found to be better resolved in this buffer system that in solution containing Triton X-100 only. Nearly 200 protein spots could be visualized on the silver stained gels. PMID- 2251793 TI - [Mechanism of impairment of calcium metabolism caused by toxin T-2; the role of the vitamin D-dependent endocrine system]. AB - Functions of the vitamin D-dependent endocrine system were studied in rats deprived of the vitamin after administration of T-2 toxin. Impairments of calcium metabolism, alterations in the enzymatic activity related to vitamin D3 bioactivation and receptor binding of the hormonal form 1,25(OH)2D3 were similar both in rats deprived of vitamin D, treated with T-2 toxin within 5 days at a dose of 0.54 mg/kg and in the corresponding controls. At the same time, reduction of the calcium metabolism patterns was retarded in rats obtaining vitamin D3 simultaneously with T-2 toxin. This effect was expressed as a decrease in normalization of 25-OHD concentration in blood, absence of renal I-hydroxylase 25 OHD3 activation, inspite of the higher content of parath hormone in blood and of cAMP in kidney, while concentration of bound 1,25(OH)2D3 receptors was distinctly decreased in tissues-targets in vivo. Thus, the effects of T-2 toxin on the vitamin D-dependent endocrine system were manifested as development of the vitamin, secondary deficiency, as resistance of I-hydroxylase 25OHD3 to regulating effect of parath hormone as well as inhibition of interaction between the complexes 1,25(OH)2D3-receptor and chromatin. PMID- 2251794 TI - [Clinico-biochemical evaluation of the effectiveness of diet therapy in gastroenterologic patients]. AB - Dissimilar immunochemical, protein and vitamin parameters were found in blood of patients with gastroenterological diseases at the initial step of impairments under conditions of routine and special diets. Specific alterations in content of transferrin, haptoglobin, tocopherol as well as in glutathione peroxidase and glucose-6-phosphate dehydrogenase activities showed that compensatory mechanisms were maintained better under conditions of the special diet therapy. PMID- 2251795 TI - [Changes in the lipid composition of mitochondrial membranes during succinate oxidase reaction]. AB - Content of lipids, free cholesterol, cholesterol esters, phospholipids and fatty acid composition were studied in mitochondria incubated in samples containing succinate. Induction of lipid peroxidation, production of malonic dialdehyde and alterations in membranes fluidity were not detected in the preparations of mitochondria within 3 hrs of succinate oxidation. Self-inactivation of mitochondria appears to occur due to an increased uncoupling of oxidative phosphorylation. PMID- 2251796 TI - [Age-dependent characteristics of metabolism of DNA precursors in healthy women, patients with mastopathy and breast cancer]. AB - Activities of thymidine kinase, thymidine phosphorylase, adenosine deaminase and 5'-nucleotidase of AMP were studied in blood serum and lymphocytes of healthy women, patients with mastopathy and with mammary gland cancer of 23-70 years old. Age-dependent alterations in the enzymatic activity were detected in blood serum of healthy women. Activity of thymidine kinase was increased simultaneously with a decrease in thymidine phosphorylase activity in 36-70 years old oncological patients, while adenosine deaminase activity was increased in patients with mastopathy and with mammary gland cancer of all the age groups. Dynamics of the enzymatic activity studied before and during chemotherapeutic treatment may be used as one of biochemical tests for evaluation of the therapy efficiency in oncological patients. PMID- 2251797 TI - [Interaction of eukaryotic aminoacyl-tRNA-synthases with polyribosomes]. AB - Properties of rabbit liver tissue aminoacyl-tRNA synthetases, associated with polyribosomes, were studied under conditions of normal state and within 12 hrs after simulation of myocardium infarction. Under conditions of myocardium infarction the activity of some forms of aminoacyl-tRNA synthetase was decreased in polyribosomes and protein fractions, liberated from polyribosomes by means of washing with buffer containing 0.5 M KCl. Polyribosomes stimulated the synthetases and protected them from heat inactivation. Deterioration of the synthetases interaction with polyribosomes appears to be among the factors responsible for impairment of protein biosynthesis under conditions of myocardium infarction. PMID- 2251798 TI - [The effect of enterosorption on lipid peroxidation and antioxidant activity of liver and blood lipids during combined thermal injury]. AB - Enterosorbents IHANT, VUGS and PMS decreased considerably the lipid peroxidation products content in liver tissue within 3 days after combined thermic trauma. The effect observed appears to occur due to adsorption of endotoxins including lipid toxins in gastrointestinal tract. Content of lipid peroxidation products in liver tissue under pathologic conditions may serve as a criterion in evaluation of enterosorbents efficiency in gastrointestinal detoxication. PMID- 2251799 TI - [Glycosaminoglycans in leukocytes of children with bronchial asthma]. AB - Content of hexuronic acids, hexoses and hexosamines was studied in lymphocytes and polymorphonuclear leukocytes of 56 children with bronchial asthma. The disease step-dependent alterations of the patterns studied were detected. Treatment of these children with bronchospasmolytic drug clenbuterol and with immunomodulator taktivine affected positively the bronchial asthma attack, which was followed by specific alterations in the carbohydrates content. Structural modifications of glycosaminoglycans in lymphocytes and phagocytes appear to be of importance for formation and development of allergic reactions in children with bronchial asthma. PMID- 2251801 TI - [Turnover of microsomal hemeproteins in the guinea pig liver during food sensitization]. AB - A phase-dependent type of microsomal hemoproteins turnover in liver tissue, estimated by incorporation of 14C-amino-levulinic acid, was detected in guinea pig males in dynamics of alimentary sensitization (1, 7, 14 and 21 days) with ovalbumin and bovine blood serum albumin (BSA). The first phase was expressed as elevated catabolism of microsomal cytochromes simultaneously with a decrease in their turnover; the second phase involved an increase in the hemoproteins biosynthesis. Less distinct sensitization with BSA exhibited the shortened period of the first phase, while activation of aminopyrine N-demethylase and aniline p hydroxylase as well as considerably increased rate of microsomal cytochromes turnover were found during the second phase in liver tissue. PMID- 2251800 TI - [Structure and properties of collagen in leukemia]. AB - Collagen I was isolated from human bone tissue and from mice bone tissue of the AKR-50 strain at the pronounced stage of leukosis. Dissimilarity of native and leukemic collagens was exhibited after evaluation of their amino acid composition, electrophoretic mobility in polyacrylamide gel containing SDS, content of the carbohydrate moiety as well as of isopoints, elution profiles in reverse-phase chromatography and gel filtration and electron microscopy of SLS crystallites. Impairments of collagen processing in leukemia appear to be responsible for its alterations in structure and properties. PMID- 2251802 TI - [The effect of surgical stress on DNA synthesis in liver and brain cells]. AB - Distinct alterations in the rate of DNA synthesis (an increase in the rate of reparation and a decrease in the rate of replication in nuclei and mitochondria) were detected in liver and brain cells during the stress caused by surgical operation. Within 8-10 hrs after the operation the rate of DNA reparation was increased by 40-50% in nuclei of liver cells and by 31-35% in brain cell nuclei. Replication of nuclear DNA was decreased immediately after the operation--by 33% in liver cells and by 50% in brain cells. Within a day after the operation the rate of replication was restored up to the control level in liver cells, while it was still decreased by 30% in brain cells. The rate of mitochondrial DNA synthesis was slightly decreased within the first 12 hrs after the operation: by 12-14% in liver cells and by 18-20% in brain cells. The stress, and particularly postoperative stress, exhibited pronounced action on structure and various systems of DNA synthesis in cells of various tissues. PMID- 2251803 TI - [The effect of adenosine on the distribution of glucocorticoid receptor complexes in rat thymocytes]. AB - In presence of adenosine (10(-7)-10(-6) M) content of nuclear 3H-hydrocortisone receptor complexes was increased in rat thymus lymphocytes, while amount of these complexes was decreased in cytosol of these cells. DEAE-cellulose chromatography of the 3H-hydrocortisone-receptor complexes demonstrated that adenosine 1.10(-6) M altered the ratio between active and non-active forms of the hormone-receptor complex. Adenosine appears to regulate transformation and translocation of the glucocorticoid-receptor complexes into the cell-target nuclei cAMP-dependent apparatus. PMID- 2251805 TI - [Identification of cholesterol esters using topological criteria]. AB - Cholesterol esters obtained from biological sources were separated using highly effective liquid chromatography. Identification of individual molecular forms of these esters was carried out by means of linear correlation between the period of their retaining and the topological indices by Balaban and Randich, describing the structure of descriptors (acyl group) in cholesterol esters. PMID- 2251804 TI - [Levels of extracellular DNA and polyamines as criteria of resistance to chemotherapy in patients with acute leukemia]. AB - Content of polyamines and extracellular DNA were studied in blood of patients with acute leukoses which did not respond to chemotherapy. Concentration of total polyamines was distinctly lower in blood of patients with acute lymphoblast and myeloblast leukoses as compared with healthy persons. Free and total polyamines were unaltered in blood of these patients after cytostatic therapy. In the patients with acute leukoses content of extracellular DNA was 2-fold higher as compared with controls. The high DNA content was maintained during the therapeutic course. Absence of any alterations in the biochemical patterns studied suggest that the patients with acute leukoses did not respond to the course of treatment used. PMID- 2251807 TI - [Differential forms of self-directed study of biochemistry in medical schools]. AB - Methods of self-directed study of biochemistry by students are considered in connection with initial levels of their theoretical knowledge and laboratory experience. This type of training involved individual tasks and free discussion on the results obtained. Optimal results were observed in organization of self directed work in small groups. PMID- 2251806 TI - [A modified method of isolation of Langerhans islets from the rat pancreas]. AB - A simple procedure is developed for isolation of Langerhans islands (LI) from rat pancreas. Homogenization of pancreatic tissue was carried out using two "Record" syringes equipped with needles of various diameter. Collagenase was not used in the procedure. After homogenization LI were individually separated using stereomicroscope. The insulin-producing capacity of LI was estimated by assay of immunoreactive insulin content in LI and in the incubation media at 0 degrees and 37 degrees as well as by their reaction to various concentrations of glucose. The procedure enabled to isolate functionally active LI and to study biosynthesis and secretion of insulin in vitro. PMID- 2251808 TI - [Antioxidants in the chemotherapy of tumors]. PMID- 2251809 TI - [The prospects for using nonsteroidal anti-inflammatory agents in the treatment of malignant neoplasms]. PMID- 2251810 TI - [The role of macrophages in tumor growth]. PMID- 2251811 TI - [DNA methylation in human lung tumors]. AB - Nucleotide profile and level of methylated cytosine (5-MC) were evaluated in DNA obtained from lung tumors in males. The level of 5-MC in DNA in malignant tissue (1.7 +/- 0.1 mol%) was half as much again that of normal lung (1.1 +/- 0.1 mol%), the difference being statistically significant. PMID- 2251812 TI - [The preoperative embolization of the hepatic artery in patients with malignant liver tumors]. AB - Hepatic artery embolization (HAE) was performed in 4 patients with liver tumors 5 60 days prior to radical resection. No adverse effects of HAE on the liver or gallbladder were observed at surgery. Intraoperative blood loss was reduced in 2 patients. Surgery was completed with intraportal chemotherapy. At 6-26 months post-surgery, all the patients were alive with no evidence of disease. It was concluded that preoperative HAE may be used in treatment of liver malignancies. PMID- 2251813 TI - [High methotrexate doses in the treatment program for acute lymphoblastic leukemia and lymphosarcoma in children]. AB - Tolerability and efficacy of high-dose methotrexate was studied in 70 pediatric patients with lymphoblastic tumors (acute lymphoblastic leukemia and non Hodgkin's lymphoma). Methotrexate was given by 24-hour infusion of 500-1000 mg/m2 (total dose-700-3000 mg) after remission had been achieved. An antidote--calcium folinate--was administered 24 hours postinfusion. Major adverse side-effects involved were stomatitis, hepatotoxicity and fever. Survival in the study group was higher than in controls. PMID- 2251814 TI - [Changes in protein metabolism and the free amino acid profile in bladder cancer]. AB - Protein metabolism status was assessed by standard procedures versus tumor stage and nitrogen-excreting function of the kidneys in 250 cases of urinary bladder cancer. In addition, 18 amino acids in the blood were assayed in 63 patients. Standard methods of examination identified protein metabolism disturbances in patients with stage III-IV renal failure whereas amino acid profile showed changes at a much earlier stage. Patients with T3-4 tumors revealed decreased blood amino acid levels. Renal failure and surgical trauma caused the level of most amino acids checked to decrease. The need for correction of the amino acid profile of the blood before and after surgery is discussed. PMID- 2251815 TI - [A method for predicting the course of chronic myeloleukemia]. AB - The effects of a synthetic prostaglandin E1 (PGE1) analog on colony-forming activity in agar cultures of peripheral blood and bone marrow was studied in 28 patients with chronic myeloid leukemia and 9 hematologically healthy subjects. Addition of PGE1 to normal bone marrow culture was followed by a significant drop in the number of colonies per dish in 8 out of the 9 subjects. In leukemic patients, the effect was bizarre. It proved to be in correlation with survival thus suggesting that the effect of PGE1 on colony-forming activity of granulocyte macrophage precursors be used in predicting survival in patients with chronic myeloid leukemia. PMID- 2251816 TI - [Endogenous factors in the development of leukoplakia and kraurosis vulvae]. AB - Levels of tropic hormones of the pituitary, glucocorticoids and male and female sex hormones were assayed in 17 cases of kraurosis and leukoplakia of the vulva prior to treatment. Most patients revealed an abnormally high androgen/estrogen ratio, elevated level of glucocorticoids and low concentrations of thyrotropic hormone, prolactin and T3. The above disturbances are closely related and interdependent. PMID- 2251817 TI - [The effect of iron carrier proteins on the transplantation of H-2 locus incompatible bone marrow in irradiated mice]. AB - Rabbit bone marrow supernatants were fractionated and purified by Ultrogel and Superose chromatography. A unique fraction promoted engraftment of allogenic bone marrow and enduring hemopoietic chimerism across the histocompatibility (H-2) barrier in lethally irradiated mice. This fraction analysed by reducing SDS-PAGE electrophoresis and transblotted on PVDF membrane or purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main pre-albumin band that was examined for primary structure by Edman degradation. It appeared to be rabbit transferrin. Iron saturated human transferrin, lactotransferrin and egg transferrin (conalbumin) were then tested in irradiated C57B1/6 mice transplanted with bone marrow from histoincompatible BALB/CJ donors. Most mice treated with iron-loaded transferrins survived and developed enduring allogeneic chimerism with no discernible signs of graft-versus-host disease at 10 months posttransplant. Observation of these animals is still carried on. Iron carrier proteins seem to provide a novel unexpected means for achieving a successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations and may open a new approach in the clinical area. PMID- 2251818 TI - [The individual characteristics of the excretion of benzo(a)pyrene metabolites in rats]. AB - Assessment of individual peculiarities of carcinogen metabolism in the body opens up new vistas in predicting individual sensitivity to these agents. The authors developed a spectrofluorometric [correction of spectrofluorescence] technique to assay concentrations of carcinogenic benzo(a)-pyrene (BP) metabolite (7,8-BP) and a product of its detoxication (3-BP) in excreta of male rats who had been given a single dose of 200 mg/kg of benzo(a)pyrene intraperitoneally. Ten-thirty times daily variations in individual levels of both metabolites were accompanied by less variation in their total amount. Parameters of BP metabolism perhaps can be used for predicting individual risk of BP-induced tumor development. PMID- 2251819 TI - [A "wrapping-up" gastrointestinal anastomosis]. AB - Formation of "wrapping" gastrointestinal anastomosis is suggested to reduce lethality after subtotal resection of the stomach for cancer in patients at high risk for pyo-septic complications. The procedure allows to completely avoid anastomotic leakage and thus decreases lethality by half. PMID- 2251820 TI - [The cytological diagnosis and classification of tumorous and nontumorous lesions of the pancreas]. AB - The paper summarizes the cytologic features of tumor and non-tumor pathology of the pancreas observed in 108 cases. Cytologic examination proved highly (90%) reliable in differential diagnosis of pancreatic pathology. A cytologic classification of pancreatic lesions is suggested. PMID- 2251821 TI - [The role of colonoscopy in screening for tumors of the large intestine]. AB - In 1986-1988, 6434 patients underwent colonoscopy in general hospital: 2076 were at risk for large bowel cancer whereas in 4358 the procedure was used for prophylaxis. Benign polyps or polyposis were detected in a total of 1699 (26.4%) patients: 856 (41.2%) in the risk group and 843 (19.3%) in the prophylactic one. Malignancy was diagnosed in 248 (11.9%) and 41 (0.9%) patients, respectively. It was found that small and early tumors made up 22% of the total number of cancers in the prophylactic group and 16.9% in the high risk group only. Colonoscopic screening carried out under general hospital condition is psychologically and economically justified since it allows to form a risk group and diagnose early cancer whereas timely removal of polyps assures secondary prophylaxis of large bowel cancer. PMID- 2251823 TI - [The late results of the surgical treatment of patients with cancer of the sigmoid and rectum]. PMID- 2251822 TI - [The importance of echography in the diagnosis of precancer and cancer of the endometrium]. AB - Ten-year experience with ultrasonography was gained at an outpatient center. Within this period, 27000 examinations were performed in 11996 females. The credibility of the method in diagnosing endometrial pathology was 85.8%. Cancer morbidity for the last 5 years was compared in the ultrasonography and no ultrasonography groups. Endometrial cancer morbidity was 6.2 times higher in the latter group. Large-scale application of the procedure followed by adequate treatment assures significantly lower incidence of said pathology. PMID- 2251824 TI - [A combination of carcinoid of the appendix and cancer of the ascending colon]. PMID- 2251825 TI - [The potentials for optimizing the treatment of III-stage squamous cell cancer of the oral mucosa]. PMID- 2251826 TI - [Separation and purification of the toxic protein of Bacillus sphaericus Ts-1]. AB - Bacillus sphaericus strain Ts-1 is highly insecticidal to larvae of the mosquito. It's insecticidal component is toxic proteins. The toxin was extracted from spore crystal complexes by disruption in a Sonicator Cell Disruptor Model W-220F followed by treatment with 0.05 mol/L NaOH. Fraction recovered from chromatography of the spore-crystal complexes on column of Sephadex G-200 were assayed against mosquito larvae and the toxic fractions from gel chromatography were subjected to SDS-PAGE. The toxic proteins in B. sphaericus Ts-1 spore crystal complex migrated in position corresponding to 42kD and 43kD. Bioassay of the two purified proteins prepared by PAGE indicated that they were all toxic to mosquito larvae. Toxic protein was further purified by DEAE-cellulose chromatography. The toxic protein with a molecular weight of 42kD was obtained. PMID- 2251827 TI - [A new serotype of Shigella boydii]. AB - Two strains which belong to the same serotype of Shigella were isolated from the bloody-pus stool of two patients (in 1986) and is reported in this paper. The results were identical both showing agglutination in low titer with serotype 8 of S. dysenteriae and serotype 4 of S. boydii when the two strains were checked well with all kinds of diagnostic antisera and vice versa, ie the antisera produced by the two strains were also checked well with sera prepared with the representative strains of all Shigella spp. No cross agglutination with O6, O7, and O150 of E. coli were found. Consequently, It appears to be a new serotype of Shigella. These two strains possess the ability of causing keratitis in guinea-pigs as well as invading epithelial cells, the DNA of both strains in agarose-electrophoresis showed a large plasmid, indicating that they are virulent strains possessing invasive ability. It was concluded that these two strains belonged to Shigella boydii as they fermented mannitol and non-related antigenically with Shigella flexneri. Since serotype 1-18 of S. boydii have been reported recently, we propose that this new serotype should be serotype 19 of Shigella boydii. PMID- 2251828 TI - [Mutagenesis of vitamin B2 producer by using protoplasts]. AB - Studies on preparation, regeneration and ultraviolet-mutagenesis of protoplasts of vitamin B2 producer Eremothecium aohbyii were reported. By using a complex enzyme system (0.5% snial digestase + 0.5% cellulase), a great number of protoplasts were obtained. Ultraviolet-mutagenesising positive mutation ratio is 14.29%. The HPLC analysis indicated that a lot of mutants were screened by using ultraviolet-mutagenesis mutation of protoplasts, Vitamin B2 produced by the mutant E3 increased 116.4%. PMID- 2251829 TI - [Enzyme-linked immunosorbent assay of larvicidal toxic proteins of Bacillus sphaericus Ts-1]. AB - Bacillus sphaericus Ts-1 Mosquito larvicidal toxins 42 k Da and 43 k Da were isolated by Sephadex G-200 chromatography. Three strains of highly toxic B. sphaericus and two non toxic strains were screened for toxic proteins using ELISA. The lowest detectable toxin level was 1.56 X 10(-5) mg/ml. Non toxic strains did not produce antigens reacting to either the 42 kDa or the 43 kDa antibodies. Ts-1 cultures were examined at 12 and 24 h by LC50 bioassay against Culex pipiens. The LC50's at 12 h and 24 h were 0.71 ppm and 0.154 ppm, respectively, i.e., the toxin level at 24 h was 4.6 times the level at 12 h. ELISA tests established total toxin at 0.049 mg/ml and 0.225 mg/ml at 12 h and 24 h, respectively, confirming the LC50 study. PMID- 2251830 TI - [Survey of Bacillus thuringiensis and Bacillus sphaericus from soils of four provinces of China and their principal biological properties]. AB - A number of isolates of Bacillus thuringiensis and Bacillus sphaericus were obtained from soils of Southwestern Area and Shaanxi Province of China. Among isolates of B. thuringiensis were under 13 sorts of serotype in total of 23 sorts of B. thuringiensis and about 20% of auto-agglutinate strains. Rules of ecologic distribution of two sorts of bacteria were analysed. Toxicities on six species of insects, morphology and crystal proteins of B. thuringiensis, as well as toxicities, morphology and crystal proteins of B. sphaericus, were investigated. 22 strains of more efficient of B. thuringiensis and 2 strains of more efficient of B. sphaericus were obtained. It was shown that B. thuringiensis is actually soil microorganism, and resource of B. thuringiensis is much fruitful in Southwestern Area of China. PMID- 2251831 TI - [Establishment of standard strains of serotypes (groups) of Streptococcus pneumoniae in China]. AB - Streptococcus pneumoniae is an important human pathogen which is responsible for life-threatening infections such as pneumonia, bacteremia and meningitis as well as for less severe but highly prevalent diseases such as otitis media and sinusitis. The number of serogroups (types) of Streptococcus pneumoniae found in the world is total 46 groups or 83 types according to typing system of Statens Serum Institute, Copenhagen, Denmark. The standard strains established in our lab of 42 groups or 67 types distributed in 17 different regions in China. The significance of this study is that two of the new serotypes (10C, 16A) are first reported in the literature in which the microbes were the agents causing pneumococcal infections. Our standard strains also include some serotypes on rare occasions such as 19C and 22A and 33C which have been found only in Asia. Our findings not only increase the total number of known types of pneumococci from 83 to 85, but also indicate that China has made progress in the field of pneumococcal research. It is the first time to report establishing a series of standard strains of pneumococci involving many serotypes (groups) in China. The work is necessary as a preliminary for pneumococcal disease prevention and treatment. The standard strains listed here with providing the resource of strain and scientific basis for developing vaccine and biological products. PMID- 2251832 TI - [Classify species of Pseudomonas pseudomallei into serotypes]. AB - Species of P. pseudomallei can be classified into two serotypes, serotype I and serotype II, based on whether or not it contains a thermolabile antigen beside a thermostable one. Under the condition of lack of typing serum, by means of serum absorption test, we recognized a strain which contains a major thermolabile antigen. The antigen was purified by Sephadex G-200, and it was used to inoculate rabbits. With the immunoserum at hand, we identified 68 of the domestic chinese strains and 6 of alien strains for serotyping by bi-directional agar diffusion test. The results showed that 68 strains were identified serotype I, 3 strains serotype II, and the remaining 3 comparable with those reported indicating that strains of serotype I were found mostly in Asia, and that the serotype are unrelated to their existing environments, nor that of animal bodies, but connected with their existence in geographic distribution. PMID- 2251833 TI - [The preparation and properties of catechol-1,2-dioxygenase from Pseudomonas putida]. AB - Catechol-1,2-dioxygenase (EC 1.13.11.1) catalyzes the degradation of catechol to cis, cis-muconic acid. The biochemical properties of catechol-1,2-dioxygenase from Pseudomonas putida 84103 were investigated. The optimum pH and temperature is 7.5-8.0 and 25-30 degrees C, respectively. Cu2+, Zn2+ inhibit the enzyme activity. The paper chromatograph and UV absorption spectrum of enzymatic reaction product are accordance with those of the standard muconic acid. PMID- 2251835 TI - [Osteoporosis]. PMID- 2251834 TI - [Demonstration of the presence of Methanobrevibacter in a colon cancer Chinese patient]. AB - A fecal specimen from a Chinese patient (85-year-old man) suffering from colonic cancer was examined for the presence of methane-producing bacteria. As a result, a Methanobrevibacter organism was isolated. Our isolate did not grow in the presence of bile salts, a result different from Methanobrevibacter from healthy Americans' feces by Miller et al. PMID- 2251836 TI - [The epidemiology of osteoporosis]. AB - In this paper risk factors and distinctive criteria between Typ I and Typ II osteoporosis are reviewed. In addition, data about fracture incidence and bone mineral content in different populations are presented. Lifetime risk for fractures is estimated and compared with that of other common diseases. It is concluded, that further improvement of bone mass measurement is necessary to identify women at risk for osteoporosis in order to initiate appropriate treatment and avoid fractures. PMID- 2251838 TI - [Radiological diagnosis of osteoporosis]. AB - The roentgen-morphologic findings of "osteoporosis" in the different regions of the skeleton are demonstrated. A combination of osteoporosis and osteomalacia induced by hormonal and metabolic bone diseases occur frequently. The results of sequential studies are discussed. Diagnostic informations obtained by quantitative radiology, especially by different methods like x-ray morphometry, densitometry with gamma-rays of isotopes of different energies, quantitative computed tomography, and imaging analysis with electronic methods are described. The sequential use of diagnostic imaging techniques in cases of suspected osteoporosis are explained. PMID- 2251837 TI - [Role and possibilities of pathology in the diagnosis of osteoporosis]. AB - Iliac crest biopsy and clinical laboratory investigations are the important criteria to diagnose metabolic osteopathies and osteoporosis. The technic of iliac crest biopsy, the histological technic and the histomorphological and histometric criteria will be discussed. The necessity to compare clinical data with the histomorphology and the importance of surgical pathology, especially osteopathology, will be emphasized. PMID- 2251839 TI - [Differential diagnosis in osteoporosis]. AB - Osteoporosis is a so called metabolic osteopathy. Under this term alterations are included concerning primary the bone tissue, but in consequence disable bone organs. Into this group of affections belong also the osteomalacia, the parathyreogenic osteodystrophy, the osteosclerosis caused by systemic changes of the bone tissue turn-over and furthermore different combinations of such alterations. For their principal diagnosis in every single case the histological findings are most important for their pathogenetic differentiation and for the (therapeutically and diagnostically important) individual specification anamnesis, X-ray findings and several biochemical parameters are important. PMID- 2251840 TI - [Clinical aspects of osteoporosis]. AB - The development of osteoporosis is a multifactorial process. Part of contributing factors are not to be influenced, others may be avoided or prevented. The achievement of an optimal peak bone mass as well as its maintenance require sufficient sex hormones in connection with optimal calcium supply with the nourishment and sufficient physical exercise. During the preclinical phase of osteoporosis only the analysis of risk factors is possible. There are no clinical symptoms of the condition itself. Manifestation of osteoporosis is documented by crush fractures or discontinuing fractures. In osteoporosis type I the vertebral column is involved. Back pains and loss of body height are the consequences leading to diminished quality of life. The pain syndrome is unspecific and may be caused by other diseases, too. In osteoporosis type II in addition peripheral fractures at disposed sites show up (neck of femur, distal radius = Colle's fracture). During aging the diminished bone mass presumably becomes less decisive for the fracture risk whereas the significance of impaired eye sight, loss of hearing, delayed reflexes and diminished muscle strength increases. For evaluating clinics of osteoporosis systems for grading are mandatory. PMID- 2251841 TI - [Current aspects of fluoride therapy of osteoporosis]. AB - Fluorine has an effect on the bone, it increases both the number and the activity of osteoblasts and, thus, at first leads to an osteoidosis. The mineralization is somewhat lagging behind. This mode of action is best suited for low-turnover osteoporosis. For all other forms of osteoporosis, such as high-turnover osteoporosis, osteoporomalacia and mixed osteopathies, fluorine therapy as the sole treatment is not optimal. In our opinion, it is not the action principle "fluorine" that is insufficient or dangerous, but the indication for this therapy was not given in case of treatment failures or certain side effects. The decisive progress in the treatment of osteoporosis is to be expected from an essentially improved and pathophysiologically oriented differential diagnosis and the resulting differential therapy. PMID- 2251842 TI - [Osteoporosis and estrogens]. AB - 5 major risk factors for osteoporosis have been identified: age, initial bone density, the menopause, bioavailability of calcium, and sporadic factors. Age appears to be the major determinant of bone mass. During a lifetime, a woman will typically lose 50% of her trabecular bone and 35% of her cortical bone. Bone density is affected by the amount of bone developed during growth, as well as by the subsequent rate of loss. Strong evidence has shown that loss of ovarian function leads to an accelerated phase of bone loss. Bone turnover rates increase, but resorption occurs faster than formation. This acceleration slows with time, reaching the level of the underlying slower phase of bone loss approximately 10 years after the onset of menopause. The role of calcium intake in preventing osteoporosis remains a matter of debate. Other factors shown to affect the risk of osteoporosis include low weight, smoking, alcohol intake, and degree of physical activity. The fact that not all postmenopausal women develop osteoporosis suggest that other, as yet determinant factors may play a role in this condition. PMID- 2251843 TI - [The role of calcitonin in osteoporosis therapy]. PMID- 2251844 TI - [Physical therapy in osteoporosis]. AB - The aims of physical therapy in the treatment of osteoporosis are lying in inhibition of progression of the degenerative process and combat of the symptoms. There is no chance of being cured of manifest osteoporosis but we can try to keep a "status presens" for giving the patient a possibility of an adequate quality of life. The used methods are mechanotherapy, electrotherapy and thermotherapy. Cryotherapy as an assisting method and therapeutic exercises especially act as a preventive measure against decreased function of locomotor system. All the other kinds of therapy try to reduce the principle symptom as pain and to produce an improvement of the general condition of the trophic situation. PMID- 2251846 TI - [Osteocalcin]. AB - The serum levels of osteocalcin, a 49 amino acid bone matrix protein have been found to represent a specific biochemical parameter of bone formation. The serum osteocalcin levels are influenced by age, sex and the time of blood sampling. In various studies on osteoporosis, endocrinopathies and other diseases which might be associated with bone disorders, the determination of serum osteocalcin levels has been proved to be an interesting research tool. However, further studies are necessary to clarify, whether the measurement of serum osteocalcin levels should be recommended in general clinical praxis. PMID- 2251845 TI - [Renal osteopathy]. AB - The pathogenesis of renal osteopathy is multifactorial. Disturbances in calcium phosphorus metabolism leading to the development of secondary hyperparathyroidism, abnormalities in vitamin D and beta-2-microglobulin metabolism, and aluminum intoxication are the most important factors. In this overview the clinic, diagnostic and therapeutic procedures of the renal osteopathy are presented. PMID- 2251847 TI - [Emergency medicine today]. PMID- 2251848 TI - [Conservative therapy on cholelithiasis]. PMID- 2251849 TI - [Prevention of malignant neoplasms]. PMID- 2251850 TI - [Bacterial adhesion as a pathogenetic factor in infections]. PMID- 2251851 TI - [Cardiopulmonary resuscitation in childhood]. PMID- 2251852 TI - [Pigeon tick dermatitis]. PMID- 2251853 TI - [Methodical aspects in the analysis of intramural morbidity as exemplified by the diagnosis cholelithiasis]. PMID- 2251854 TI - [Family practice and social care of elderly citizens in an urban new construction area]. PMID- 2251855 TI - [Robert Remak (1815-1865). A jewish physician and researcher between recognition and rejection]. PMID- 2251856 TI - [Remembering Hermann Zucker]. PMID- 2251857 TI - [Control of the use of bovine somatotropin (bST) by the determination of bST and insulin-like growth factor I (IGF-I) in blood and milk of cows]. AB - bST, a milk production-enhancing compound not yet registered in the EG and the USA, has been evaluated as safe for the consumer. Nevertheless, actual discussions include a possible ban of applications; therefore, effective measures of control are demanded. The evaluation of bST plus IGF-I in blood only allows a monitoring of bST treatment. Under the condition of two blood samplings from each cow with a 7-day interval and the favorable experimental design (1. sampling rigorous on days 4 or 6 after injection of a bST depot preparation), an efficiency of 96% correct evaluations could be obtained; under field conditions, despite analytical efforts, about 20% false estimations must be taken into account. There is no means of monitoring milk and other products of cows treated with bST, hence analytical measures for the control of imports seems to be useless. PMID- 2251858 TI - Effects of short chain fatty acids and K on absorption of Mg and other cations by the colon and caecum. AB - The influence of short chain fatty acids (SCFA) on Mg, Na, and water absorption was studied in the rat distal colon and caecum using an in vivo luminal perfusion technique. The effect of SCFA on K absorption by the distal colon and the effect of K on Mg absorption by the distal colon and caecum were also investigated. Butyrate (60 mmol/l) or a mixture of SCFA (60 mmol/l acetate, 20 mmol/l propionate, 10 mmol/l butyrate) stimulated Mg and K absorption by the distal colon, while Na and water absorption was not affected. The effect on Mg absorption was pH-dependent. In the caecum, butyrate enhanced Na and water absorption, but not Mg absorption. Acetate (60 mmol/l) did not influence electrolyte absorption by either intestinal segment. K (30 mmol/l) inhibited Mg absorption by the distal colon, but not by the caecum. It is concluded from these findings that SCFA deriving from fermentation of carbohydrates in the large intestine stimulate Mg, K, and Na absorption by delivering protons to Mg++/H+, K+/H+ and Na+/H+ exchangers located in the apical membrane of the epithelium. K seems to inhibit Mg absorption in the colon by affecting a mechanism which does not respond to SCFA. PMID- 2251859 TI - [Effects of different vitamin D metabolites on the leg weakness syndrome of turkeys]. AB - In two experiments the influence of vitamin D metabolites on leg weakness in turkeys belonging to the Big 6 line was studied. The metabolites were given orally or intravenously in different dosages. There are no differences in vitamin D-dependent parameters between healthy turkeys and turkeys with leg weakness. Additional oral application of 1,25 (OH)2D3 in dosages of 2, 5 or 10 micrograms per animal day and of 400 micrograms 25 (OH)D3 per animal day had no influence on leg weakness. Even after intravenous application of 2 or 5 micrograms 1,25(OH)2D3 per animal day there were no changes concerning the degree of leg weakness nor were any signs of hypervitaminosis D observed (increase of serum calcium level or increase of the activity of duodenal calcium binding protein). Our results indicate that this form of leg weakness in turkeys is not connected to a disturbance of vitamin D metabolism. PMID- 2251860 TI - Parenteral beta-carotene administration to cows: effect on plasma levels, lipoprotein distribution and secretion in the milk. AB - Beta-carotene has been considered to have a positive effect on fertility. Therefore the effect of a parenteral administration (intravenous or intramuscular) of beta-carotene on plasma levels, its distribution among the lipoprotein fractions and its secretion in the milk was investigated in cows. A single parenteral administration of beta-carotene resulted in a marked increase in total beta-carotene in the blood. Low density lipoprotein (LDL)-bound beta carotene increased rapidly in the initial phase and then remained rather constant. The proportion bound to the high density fraction (HDL), however, increased continuously, reaching maximum levels parallel to the total plasma concentration. Beta-carotene administration had no effect on vitamin A levels in plasma, but caused an increase of beta-carotene and vitamin A in milk. The results show that the parenteral administration of beta-carotene is not only an effective way to increase its blood plasma level but also results in a binding of beta-carotene to its physiological carrier--the lipoproteins. Beta-carotene is therefore supplied to peripheral target tissue by the same carriers as those when beta-carotene is administered orally. The availability of beta-carotene for peripheral tissues is further supported by the increase in beta-carotene in milk, as well as by the increase in vitamin A in milk which points to a local conversion of beta-carotene into vitamin A in the mammary gland. PMID- 2251861 TI - Studies on the ascorbic acid metabolism of callitrichid monkeys by 14C isotope excretion technique. AB - Recently it has been found that the two monkey species Callithrix jacchus and Saguinus fuscicollis, both belonging to the same New World monkey family Callitrichidae and held in the same colony under identical conditions, had extremely different serum ascorbate levels. To examine the ascorbic acid metabolism the 14C-excretion of orally given 1-14C-ascorbic acid was studied under conditions of marginal and abundant vitamin C supply and under intentional stress. There were large differences in the mode of 14C excretion between low and high ascorbate supply. The differences were smaller between stress/no stress conditions intraindividually than between the two species, but they were in the same manner. In comparable trials S. fuscicollis reacted such that a higher status of stress can be supposed in this species. PMID- 2251862 TI - [Radiotelemetric studies of the body temperature of white-tufted monkeys (Callithrix jacchus)]. AB - A newly developed telemetry system was used to study deep body temperature (BT) of two adult male common marmosets (Callithrix jacchus). The BT-curves of both monkeys showed a similar clear circadian rhythm with a range up to 3.5 degrees C. At environmental temperature of 28 degrees C (ET) the BT of the monkeys varied in the daytime dependent on their spontaneous activity, with little individual differences between 37.5 degrees C and 39.3 degrees C; at night the BT of the remarkably deeply-sleeping animals decreased to an average at 35.8 degrees C. Elevating ET up to 30 degrees C effected an increase of BT by 0.6 degrees C, both during day and night. On the contrary, reducing ET to 24 degrees C the BT increased only at night, by 0.2 degrees C at ad libitum food intake and 1.0 degrees C at fasting. Measurements of BT by inserted rectal thermometer caused, compared with telemetry, an average at 0.4 degrees C higher values. PMID- 2251864 TI - [Difficulties in the explication process with psychosomatic clients: the significance of understanding and process directedness]. AB - In the study it has been investigated in what way therapeutical interventions influence the clarification/explication processes of psychosomatic and non psychosomatic clients. It was found that therapists exert a strong influence on the clients' explication processes, that the type of the content references made by the therapist strongly influences the effects of the interventions and that the processes of psychosomatic clients are less capable of being furthered than that of non-psychosomatic clients. Theoretical and practical implications of the results are discussed. PMID- 2251863 TI - [Effects of purine-rich nutrition on the renal and extrarenal excretion of purine catabolites in Dalmatian dogs]. AB - In eight Dalmatian dogs exogenous effects (dietary purine, xylit infusion) on plasma uric acid were examined and relationships between purine intake and excretion were established. Increasing purine intake resulted in a linear increase in renal excretion of urate (r = 0.952) and a less steep increase of allantoin (r = 0.901). In pairs of two animals with low and high purine intakes the metabolic fluxes in steady state were measured by continuous infusion of (2 14C) urate. The extrarenal excretion rates of urate + allantoin during high purine and low purine feeding averaged 2.9% and 8.5% of entry rates. The results are discussed in comparison with human data and a remarkably good agreement is observed. PMID- 2251865 TI - [Diagnosing the social behavior of autistic children]. AB - This article describes a new assessment of the social behaviour of autistic children. The relevance of clinical and developmental diagnostic criteria for the social interaction with autistic children will be illustrated. A practical example stresses that new developmental psychology studies on autistic children's reciprocal interaction, analyse the social behavior in the "social context". Aspects of the social context--the social situation and the background knowledge- are used to demonstrate the construction of observation units. Those units will structure and help to control the social interaction of the examiner and the child. One observation unit consists of the interactional situation, the interactional style and the interaction behavior. The construction of several observational units as quasi-natural situations and the audio-visual record of the social behavior in those situations permit the collection of qualitative deviations in the social behavior of autistic children. Identification, differential diagnosis and therapy-orientated assessment can be based on those informations. PMID- 2251866 TI - [Ambulatory psychotherapy management (as exemplified by Urban-Basel and Rural Basel cantons)]. AB - In 1977 a cantonal regulation for the independent practice of psychotherapists, the first in Switzerland, came into effect in Basel-Stadt and Baselland. In 1982 psychologists with a postgraduate formation in psychotherapy were surveyed with a first questionnaire. A second such questionnaire has been sent out in 1988 of which the results are presented here. In Basel-Stadt (about 190,000 inhabitants) about 64 psychologists and 104 psychiatrists in private practice provide psychotherapeutic services for outpatients. In Baselland (about 233,000 inhabitants) the number of psychotherapists is roughly one fourth, indicating the center function of the city with regard to psychotherapeutic services. In the two cantons a total of 4,800 weekly therapy sessions are provided. This amounts to a sharp increase of psychotherapeutic services rendered. Inspite of an often heard trend toward group therapy individual therapies dominate with 82%. The postgraduate therapeutic formation of psychiatrists and psychologists continues to be dominated by psychoanalyticly oriented schools. The clients served by psychologists do not differ dramatically from those of psychiatrists: Mainly neuroses, psychosomatic diseases and neurotic depressions are treated, only a few addictions and psychogeriatric problems. 80% of the psychiatrists judge the effect of the regulation positively. The cooperation between psychologists and psychiatrists is closer than generally assumed. Finally some fundamental questions about the psychotherapeutic maintenance are discussed. PMID- 2251867 TI - [Method of existence analytic psychotherapy]. AB - Introducing questions of individual purpose and meaning into psychotherapy was an important contribution of Viktor Frankl and a necessary supplement to traditional psychotherapy. V. Frankls "Logotherapy" (logos = meaning) however has found its main application in counselling (especially bereavement and grief processes) and prophylactic endeavours (e.g. pedagogics). Suffering from meaninglessness, on the other hand, showed up to be a respectively rare indication for psychotherapeutic interventions in its proper sense. Thus the question was arising how to apply Frankl's valuable meaning-centered concept of man (which he called "Existential Analysis") in a genuine way to other neurosis and to personality disorders, so far "unspecific indications" to Logotherapy. This paper gives an outline and methodological foundation of "Existential Analysis Psychotherapy". A case study finally is illustrating its phenomenological proceeding. PMID- 2251868 TI - [Ontology and pathical existence. On the philosophical-medical anthropology of Victor von Weizsacker]. AB - In his medical-philosophical anthropology Weizsacker claims the introduction of the subject into the sciences insofar as they deal with man. In contrast to modern Cartisianism subjectivity is defined as pathical existence and this again considered as a polarity of activity and suffering. The manifold of the phenomena of disease and pain shows the frontiers of pure functionalism and the principle of causality in a theory of the living. Such a theory demands a principle of complementarity for the relation between being and subjectivity, between ontology and pathosophy. PMID- 2251869 TI - Potential use of live viral and bacterial vectors for vaccines. WHO meeting, Geneva, 19-22 June, 1989. AB - The use of vaccinia virus vector for the delivery of antigens was first described by Moss and Paoletti and their colleagues in 1982. Such vaccines could be of particular value in developing countries because they would be cheap, stable, easy to administer and provide long-lasting immunity. WHO recognized the potential value of such a delivery system by convening two meetings, one at the National Institutes of Health, USA in November 1984 and the second at WHO headquarters, Geneva, Switzerland in September 1985, to discuss the possibility of using such products, particularly with regard to their safety. Since that time, other vehicles which could be useful for the delivery of antigens have been described. These include Escherichia coli, Salmonella typhimurium, BCG, all other poxviruses, adenovirus, herpesvirus and poliovirus. At its meeting in July 1988, the Scientific Advisory Group of Experts of the Programme for Vaccine Development (SAGE) concluded that it was appropriate to discuss the general topic of live vectors and proceeded to arrange a meeting to discuss the present position and to prepare a report on the following key issues: requirements for safety and efficacy; immunological factors which may influence efficacy; medical constraints on use. The present report results from a meeting held in Geneva from 19 to 22 June 1989. PMID- 2251870 TI - Polio immunity to killed vaccine: an 18-year follow-up. AB - Two hundred and fifty children born in 1967 and vaccinated with killed polio vaccine in Sweden were followed for 18 years and tested for neutralizing antibodies against polio. All of them had demonstrable antibodies at the age of 18. Sixty-four children were tested in samples collected throughout the years. After a more marked fall of antibody titres during the first few years after vaccination, the decline levelled off to a mean decrease in titre of 0.05-0.10 log10 per year. In half of them, the routine vaccination comprising a fourth dose at 6 years of age was changed and this booster was postponed to the age of ten. The children given the booster dose at ten had significantly higher antibody levels at 18 years of age than those given it at six. PMID- 2251871 TI - Measles-mumps vaccination in the FRG: an empirical analysis after 14 years of use. II. Tolerability and analysis of spontaneously reported side effects. AB - Four hundred and thirty-three reports of suspected side effects following measles mumps vaccination had been received at Behringwerke by the end of December 1989. The analysis of the data shows that no new risks of the vaccination could be identified and that the frequency of side effects is in good agreement with the findings of other authors. It therefore can be assumed that the relative risks of the vaccination continue to be distinctly outweighed by the benefits. The findings clearly demonstrate once more that it is necessary to carry out a thorough differential diagnosis before one can assume that the symptoms observed are causally related to the vaccination. In addition the analysis shows the importance of the epidemiological approach to the assessment of rare side effects. PMID- 2251872 TI - Secondary analyses of the efficacy of two acellular pertussis vaccines evaluated in a Swedish phase III trial. AB - A placebo-controlled efficacy trial of two acellular pertussis vaccines carried out in Sweden in 1986-87 used culture confirmation as the principal case definition. However, the sensitivity of pertussis culture is low, and secondary analyses using more sensitive serological diagnostic criteria have therefore been carried out. These analyses confirm that vaccination with pertussis toxoid alone does protect against typical whooping cough with laboratory confirmation, but show that it does not protect against infection or colonization. There is evidence that the addition of filamentous haemagglutinin provides some protection against infection. Bacterial isolation rates were lower in vaccinated than unvaccinated children with serologically confirmed pertussis and increased with disease severity. PMID- 2251873 TI - Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines. AB - In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01. PMID- 2251874 TI - Functional role of respiratory tract haemagglutinin-specific IgA antibodies in protection against influenza. AB - Intranasal inoculation of haemagglutinin (HA) purified from influenza virus A/PR/8/34 (PR8, H1N1) together with cholera toxin B subunit, into Balb/c mice resulted in complete protection against PR8 infection in parallel with the induction of high levels of HA-specific IgA and IgG antibodies on the respiratory tract. The respiratory tract IgA and IgG were purified from nasal and lung washings of the immunized mice using affinity columns, and their HA-specific activities were measured by enzyme-linked immunosolvent, plaque neutralization and haemagglutination inhibition assays. The purified IgA and IgG had the following properties: (1) They were able to neutralize virus in vitro. (2) The purified IgA included major antibodies directed against PR8 virus and minor antibodies cross-reactive with A/Yamagata/120/86 (H1N1) or A/Fukuoka/C29/85 (H3N2) virus, while the purified IgG included major antibodies to the homotypic virus, minor antibodies to the H1N1 virus and only a trace amount of antibodies to the H3N2 virus. (3) When separated on a Sephacryl column, most of the IgA anti HA activities occurred in the polymeric fractions of purified IgA, whereas the IgG anti-HA activities occurred in the monomeric fractions. (4) When passively administered to normal mouse respiratory tract before infection, the purified IgA protected against PR8 infection. These results suggest that HA-specific, polymeric IgA antibodies on the respiratory tract by themselves provide not only protection against the homotypic virus but also higher levels of heterotypic immunity than IgG. PMID- 2251875 TI - Enhanced pulmonary histopathology is observed in cotton rats immunized with formalin-inactivated respiratory syncytial virus (RSV) or purified F glycoprotein and challenged with RSV 3-6 months after immunization. AB - Formalin-inactivated (FI) RSV, purified F glycoprotein in alum, and RSV infection (intranasal) were compared for their immunogenicity, efficacy, and ability to enhance pulmonary histopathology during RSV infection 3 and 6 months following immunization by the intramuscular route. Purified influenza virus in alum was used as a control immunogen. At 1 month following immunization with one dose of purified F glycoprotein (5 micrograms), cotton rats developed levels of F antibodies (ELISA) higher than the other groups, but these antibodies had the lowest level of neutralizing activity, Little increase in antibody titre was seen following a second dose of FI-RSV or purified F vaccine given at 1 month. Animals that received 5 micrograms F, 0.5 microgram F, or were almost completely resistant to pulmonary RSV infection following challenge at 3 months, but were susceptible by 6 months. Animals immunized with 5 micrograms of purified F glycoprotein developed alveolar and bronchiolar histopathology following RSV challenge at 3 or 6 months which was comparable to that of animals immunized with FI-RSV. These levels significantly exceeded those in animals previously immunized with influenza A virus vaccine which exhibited little histopathology. Animals previously infected with RSV also developed bronchiolar, but not alveolar, histopathology suggesting that the bronchiolar histopathology seen in RSV challenged cotton rats is a normal component of the immune resolution of RSV infection. These results suggest that the immune response of cotton rats to immunoaffinity purified F glycoprotein can result in enhanced bronchiolar and alveolar histopathology following RSV challenge. Thus, caution should be exercised in studies in humans using a purified F glycoprotein subunit vaccine. PMID- 2251876 TI - Development of a new type of influenza subunit vaccine made by muramyldipeptide liposome: enhancement of humoral and cellular immune responses. AB - The muramyldipeptide (MDP), [6-O-(2-tetradecyl-hexa-decanoyl)-N-acetylmuramyl-L isoglutamine] can be incorporated into liposomes with haemagglutinin and neuraminidase subunits were attached to the inner and outer surfaces of lamellar structures of the liposomes, probably through their hydrophobic ends. The addition of cholesterol resulted in much more stable liposomes, which were similar in size and shape to native influenza virus particles. These liposomes enhanced the immunogenicity of haemagglutinin in mice, such that the levels of antibody induced were about 16-fold higher than those of subunit haemagglutinin vaccine alone. Results of proliferation tests with spleen cells from mice and guinea-pigs were consistent with the immunopotentiation of haemagglutinin by liposomes. In addition, the higher antibody levels produced in mice, immunized with the haemagglutinin and MDP-containing liposomes (MDP-virosomes), were maintained for at least 6 months. Enhancement of the cellular immune response, measured by delayed type hypersensitivity reactions, was also observed in the guinea-pigs immunized with MDP-virosome vaccine. Preliminary tests with splenocytes from mice immunized with different vaccines also indicated that the MDP-virosome vaccine induced cytotoxic T-cell activity in these mice. This study revealed that the formation of liposomes with muramyldipeptide enhanced the level and persistence of circulating antibody, and enhanced cellular immunity in guinea pigs and mice. PMID- 2251877 TI - [Pharmacogenetic studies on analgesic activity of and physical dependence on morphine in BALB/c, C57BL/6 inbred mice and these recombinant CBF1 mice]. AB - Mice of the BALB/c, C57BL/6, and CBF1 strains were studied with respect to analgesic activity of and physical dependence on morphine. The acute administration of morphine resulted in analgesic response in the three strains with the following ranking orders: BALB/c greater than C57BL/6 = CBF1 for 5 mg/kg, and C57BL/6 greater than BALB/c greater than CBF1 for 10 and 20 mg/kg. Mice were treated with morphine-admixed food (1-3 mg/g of food) for 9 days. During the treatment, morphine intake in BALB/c was lower than those in C57BL/6 and CBF1. Thus, we examined the degree of physical dependence in three mouse strains after chronic morphine injections for 10 days. There was significant difference in naloxone-precipitated body weight loss among strains, the ranking being as follows: BALB/c greater than CBF1 greater than C57BL/6. However, there was no difference in appearance rate of naloxone-precipitated jumping, but a difference in body shakes and body weight loss, among strains. These results suggest that analgesia of and preference for morphine, and naloxone-precipitated weight loss and body shakes may be influenced by genetic factors. PMID- 2251878 TI - [Effects of BY-1949 on three kinds of experimental amnesia in rodents]. AB - The possible anti-amnesic effects of a dibenzoxazepine derivative, BY-1949 (3 methoxy-11-methyldibenz[b,f] [1, 4] oxazepine-8-carboxylate), were examined using the three learning paradigms. In the one-trial passive avoidance task in mice, BY 1949 (1-30 mg/kg, po) and aniracetam (3-30 mg/kg, po) reversed the shortening of the response latency in the retention test produced by exposure to 100% CO2 immediately after the acquisition trial. In the two-way active avoidance task in rats, BY-1949 (10, 30 mg/kg, po) reversed the decreased avoidance rate produced by the hypoxia treatment (5% O2:95% N2). In the radial-arm maze task in rats, BY 1949 (10 mg/kg, po) and aniracetam (10, 30 mg/kg, po) improved the impaired correct choices induced by scopolamine (0.25 mg/kg, ip). These results suggest that BY-1949, as well as aniracetam, exerts some improvement effects on experimental amnesia. PMID- 2251879 TI - [The effect of diazepam on exploratory behavior and its strain differences in inbred rats]. AB - The effect of diazepam on exploratory behavior was investigated in two inbred strains of rats, Fischer 344 (F344) and Lewis (LEW). The total numbers of head dips and head-dipping duration in the rat hole-board test, and the total number of rearing and locomotor activity in the open-field test were measured after diazepam administration. The numbers of head-dips and rearings, and head-dipping duration and locomotor activity in naive F344 were significantly greater than those in naive LEW (P less than 0.001), suggesting that LEW is more emotional than F344. Diazepam, 0.31 and 0.63 mg/kg for F344 and 0.31-1.25 mg/kg for LEW, increased head-dips, head-dipping duration and rearings. However, there were no strain differences in enhancing effect of diazepam on locomotor activity. On the contrary, higher doses of diazepam, 0.94-2.50 mg/kg for F344 and 2.50 mg/kg for LEW, decreased head-dips, head-dipping duration, and rearings. However, the effect of diazepam on rotarod performance in LEW was similar to that in F344. These results suggest that F344 is more sensitive to sedative effect of diazepam than LEW, and that the sensitivity to diazepam may be strongly influenced by genetic factors. PMID- 2251880 TI - Effects of psychoactive drugs on the conflict behavior under operant situation in Mongolian gerbils (Meriones unguiculatus). AB - Effects of diazepam, pentobarbital, morphine, ethanol, caffeine, and nicotine on the conflict behavior established under a MULT FR 20/FR 20 punishment schedule of food reinforcement were investigated in Mongolian gerbils. Fourteen out of 17 gerbils learned lever-press response for food within 15 sessions of training under FR 20 schedule. Although high voltage of electric shock (125-225 V) was required for attaining lever-press suppression, all 14 gerbils exhibited stable conflict behavior, i.e., showing high response rate of 20-30 responses/min in the safety period and low response rate of 0-3 responses/min in the alarm period. Diazepam, a prototype of the antianxiety drugs, increased the response rate in the alarm period. The anticonflict effect was also observed after administration of either pentobarbital or ethanol. On the other hand, morphine suppressed lever pressing in a nonspecific manner. Caffeine tended to attenuate the conflict behavior, but nicotine had no such effect. These results suggest that the effects of psychoactive drugs on the conflict behavior of gerbils are almost identical with those in mice and rats. PMID- 2251881 TI - [The molecular heterogeneity of Shigella sonnei lipopolysaccharide based on polyacrylamide gel electrophoretic data]. AB - The molecular heterogeneity of S. sonnei lipopolysaccharide (LPS), reflecting the size of lateral O-specific polysaccharide chains, has been established by the method of electrophoresis in acrylamide gel in the presence of sodium dodecyl sulfate and urea. The dominating components fall into three types, viz. those with 0-3, 10-16 and 35-40 repeating structures, the remaining components being minor ones. The electrophoretic profile of S. sonnei LPS considerably differs from the profiles of Escherichia coli and S. flexneri LPS, but coincides with the LPS profiles of other strains with different virulence. The preparations of LPS obtained by extraction with trichloroacetic acid have the same electrophoretic profiles as LPS obtained by the method of aqueous phenol extraction. The domination of certain molecular variants reflects, seemingly, specific features of the biosynthesis of LPS, characteristic of a given strain. The mechanisms of the preferable synthesis of lateral O-specific chains of the definite size and the importance of the molecular parameters of lateral chains for the biological properties of LPS require further study. PMID- 2251882 TI - [Antigenic preparations for the immunodiagnosis of candidiasis]. PMID- 2251883 TI - [The principles for organizing independent work in studying a course in microbiology, virology and immunology]. PMID- 2251884 TI - [The correction of dysbiotic disorders of the vaginal microflora by using a preparation made from highly adhesive lactobacteria]. AB - The effectiveness of a new bacterial preparation obtained from highly adhesive lactobacteria and intended for the correction of dysbiotic disturbances of vaginal microflora was studied in the treatment of 60 pregnant women with dysbacteriosis of the maternal passages. 30 pregnant women were simultaneously treated by the vaginal application of Lactobacterin. The study showed that the use of the preparation of highly adhesive lactobacteria caused the pronounced and stable correction of the microflora of the maternal passages. This correction was manifested by the domination of lactic acid bacterial flora and a decrease in the number of opportunistic microorganisms. PMID- 2251886 TI - [A comprehensive evaluation of the biological properties of the causative agents of typhoid fever isolated from patients and carriers]. AB - The biological properties of 106 S. typhi cultures were studied; of these, 59 cultures were isolated from 45 chronic carriers and 47 cultures, from 23 typhoid fever patients. According to the degree of their virulence (CPD50 in the continuous cell-line culture Hep-2), the strains isolated from the patients were more virulent than those isolated from the chronic carriers. The mean value of lg CPD50 was 5.76 +/- 0.04 for the patients and 6.86 +/- 0.03 for the chronic carriers. The strains isolated from the patients showed greater variability in the degree of their virulence. The study of the plasmid spectrum showed that 9.4 +/- 5.6% of the strains contained plasmids. From the patients plasmid-containing strains were isolated more frequently than from the carriers (14.9 +/- 2.5% and 5.1 +/- 2.9%). Multiresistance to antibiotics in combination with the presence of plasmids was detected in 6 strains isolated from the typhoid patients with morbidity having the character of outbreaks. PMID- 2251885 TI - [Lyme borreliosis in Lithuania: its prevalence, clinical picture and treatment efficacy]. AB - In 1988 Lyme borreliosis (LA) was diagnosed in 376 patients in Lithuania, including 101 patients who had the first stage of circular migrating erythema. Of this latter group, in 40 patients (39.6%) specific antibodies to the causative agent of LB were detected. All 101 patients were intensively treated with antibiotics for 10-14 days. The effectiveness of treatment was evaluated 4-5 months later. Information was collected only on 90 patients, including 82 patients who had undergone treatment. Complete convalescence was achieved in 52 cases (63.4%). 20 more persons considered themselves to be practically healthy. But in 10 patients (12.2%) the development of the disease continued, among them in 6 patients who stopped the prescribed course of treatment on their own accord. Out of 8 patients who had not yet even started to undergo treatment, 5 patients had signs of the manifest progress of the disease. Besides, information on the incubation period of the disease, its seasonal character, the characteristic features of erythema and concomitant symptoms in presented. PMID- 2251887 TI - [The adhesion of clinical isolates of Campylobacter jejuni to intestinal epithelial cells in vitro]. AB - The adhesive activity of C. jejuni isolated from feces of children with Campylobacter infection was studied with the use of a newly developed model. 47 clinical isolates were analyzed; of these, 91% were found to be enteroadhesive to a variable degree. As the result of in vitro studies, Campylobacter were found to have much greater tropism to colonic cells and epithelial cells of Peyer's patches in comparison with the epithelial cells of the small intestine. The correlation between the degree of adhesive activity and the severity of the course of Campylobacter infection in children. PMID- 2251888 TI - [Rabies prognosis in western Siberia and the regulatory factors of the epizootic process]. AB - In this article the regulatory factors of the epizootic process are considered and the spatial-temporal prognostication of rabies infection in the region is proposed on the basis of data on rabies morbidity among animals, the purchase of skins of carnivorous animals for 20-25 years, virological experiments on wild animals, calculation of the number of carnivores and small mammals, as meteorological observations. The study has shown that a variety of animal species serving as hosts for the virus and its population differences contribute to the stable existence of the infection. Rabies morbidity has been found to be positively linked with its preceding level, the number of wild animals, the height and hardness of the snow cover and negatively with the number of small mammals. PMID- 2251889 TI - [An explosive outbreak of respiratory streptococcal infection with a droplet transmission mechanism]. AB - The data obtained in the study of an explosive outbreak of acute respiratory diseases, tonsillitis and scarlet fever in one of schools in Moscow have made it possible to exclude the alimentary mechanism of its development and to demonstrate the role of the droplet mechanism of transmission in the appearance of its outbreak. The epidemiological analysis of the outbreak has permitted the formulation of the hypothesis on the conditions of the formation and spread of the epidemic variant of the infective agent; this hypothesis corresponds to the available data in literature on the qualitative changes of the infective agent in the course of the epidemic process. The study has shown that the prophylaxis of the explosive outbreaks of respiratory streptococcal infections must be ensured by the system of epidemiological surveillance with timely intervention into the epidemiological process at its early stages. PMID- 2251890 TI - [The immunobiological properties of the antigenic preparations obtained from a vaccinal strain of Klebsiella pneumoniae 204 grown in media of differing compositions]. AB - In the technology of the cultivation of K. pneumoniae vaccine strain 204 with a view to obtaining biomass for the production of antigenic preparations the traditionally used culture medium with full nutritional value has been replaced by the alternative variant of synthetic medium. The specific physiological and morphological features of this strain grown in synthetic culture medium have been studied and described. Irrespective of the composition of the culture media used for cultivation, the antigenic preparations have been shown to have no difference in their chemical composition, immunogenic and toxic properties. PMID- 2251891 TI - [The quality standardization of a national vaccine against yellow fever]. AB - One of the commercial lots of yellow fever vaccine has been attested as the National Branch Standard (NBS) of yellow fever vaccine. This NBS has been studied in all tests required by the regulations for standard vaccines. The NBS has been found to meet the necessary requirements in all its characteristics. The study of the thermostability of the NBS at temperatures of 4-10 degrees C, 20-22 degrees C, 37 degrees C during storage for 24 hours to 1 year has revealed the rapid loss of the infectious capacity of the virus at the above temperatures and its high stability during storage at -20 degrees C. Thus, the NBS has been found to retain the required level of immunizing potency for 3 months at a temperature of 4-10 degrees C, for 1 month at 20-22 degrees C and for 2 weeks (the term of observation) at 37 degrees C. The heat resistance of the NBS of yellow fever vaccine corresponds to the WHO requirements. The newly developed NBS has been used as the standard preparation for controlling 27 lots of commercial yellow fever vaccine. PMID- 2251892 TI - [The formation of a test system for assessing the safety of different types of pertussis preparations: their cytotoxic action on mouse thymocytes in vitro]. AB - The test for the evaluation of the toxicity of different types of pertussis preparations as manifested by their in vitro influence on mouse thymic cells (T test) has been finally worked out. The use of the T test has made it possible to reveal the nonstandard character of the production lots of adsorbed diphtheria pertussis-tetanus vaccines, both whole-cell vaccine and Japanese acellular vaccine. The degree of the in vitro damaging action of pertussis preparations on mouse thymic cells greatly depends on the residual content of Bordetella pertussis nontoxoidized toxin which, in contrast to B. pertussis lipopolysaccharide and filamentous hemagglutinin, produces pronounced cytotoxic action on mouse thymic cells. PMID- 2251893 TI - [An immunoenzyme system for determining antibodies to Streptococcus pneumoniae polysaccharides in biological fluids]. AB - The enzyme immunoassay (EIA) system for the determination of antibodies to capsular polysaccharides of pneumococci, serotypes 1, 3, 6B, 8, 9N, 15F, 23F, and C-polysaccharide has been developed on the basis of poly-L-lysin-modified antigens. The use of isotype-specific conjugates in this system permits the detection of IgG and IgA antibodies in different biological fluids: blood serum, pleural fluid, saliva, milk. Samples obtained from children with pneumococcal infection and from nursing mothers have been studied. As shown in this study, the EIA system can be used for the evaluation of the dynamics of pneumococcal infection in children. PMID- 2251894 TI - [A method for the experimental determination of the doses of antigen protecting 50% of animals from a series of doses of pathogenic material]. AB - A new immunological regularity has been discovered mathematically. Proceeding from this regularity, a simple index characterizing the pathological reactivity of animals has been proposed and a new (universal) method for the determination of the D50 of the antigen, i. e. doses protecting 50% of the animals receiving a series of doses of pathogenic material, has been developed and checked according to experimental data. PMID- 2251895 TI - [Antibodies to Streptococcus pneumoniae antigens in newborn infants]. AB - The levels of antibodies to capsular polysaccharide antigens of pneumococci (serotypes 1, 3, 6B, 8, 9N, 15F, 23F), C-polysaccharide and protein antigen of pneumococci in the blood sera of 38 newborn infants at the moment of their birth (umbilical blood) and on the 5th or 6th day of their life, in their mothers' blood sera, as well as in the colostrum and milk of 48 nursing women, have been studied by means of the enzyme immunoassay. The study showed that in the normal course of pregnancy antibodies to pneumococci were transferred transplacentally from the mother to the fetus. Though in most cases their content in the blood of newborn infants was lower than that in maternal blood, it exceeded the average level of antipneumococcal antibodies in children aged 3-12 months. In the milk of nursing mothers considerable amount of IgA antibodies to pneumococci was detected, which might be an additional protective factor with respect to pneumococcal infection in infants. PMID- 2251897 TI - [The immunochemical characteristics of allergens]. AB - Modern approaches to the standardization of allergens require the use of not only biological methods, but also a wide range of physicochemical and immunological ones. To obtain Soviet standard samples, the optimum spectrum of methods for their characterization, evaluation and comparison with international standard samples should be definitely selected. After the preliminary study of a number of allergens by different immunochemical methods a set of such methods, including different kinds of electrophoresis, isoelectrofocusing, immunoblotting, etc., are proposed, these methods being considered obligatory for obtaining Soviet standard samples of allergens. PMID- 2251896 TI - [Proteus peritonitis-bacteremia in mice--a model for studying postvaccinal Proteus immunity]. AB - The dynamics of the formation of postvaccinal immunity after immunization with preparations obtained with the use of hydroxylamine (HA) preparations from Proteus strains of different O serogroups, Salmonella minnesota Re-mutant and the common antimicrobial antigen isolated from Escherichia coli 14 has been studied on mice with Proteus peritonitis-bacteremia used as a model. The study has revealed that intraperitoneal immunization with Proteus HA preparations stimulates the phagocytic activity of peritoneal mononuclear cells in mice and induces an increase in the titers of specific O antibodies. Proteus antigens ensure the formation of anti-Proteus immunity, preventing the death of the animals from peritonitis-bacteremia. The protection of mice from such infection resulting from the injection of the common antigens of gram-negative bacteria is considerably less. These data are indicative of the possibility of using Proteus peritonitis-bacteremia as a model for the study of the protective potency of Proteus vaccines. PMID- 2251898 TI - [The subject of epidemiology]. PMID- 2251900 TI - [The enterotoxins of enterotoxigenic Escherichia coli: their characteristics, mechanism of action and genetic control]. PMID- 2251899 TI - [The biological and social aspects of infectious pathology in animals]. PMID- 2251901 TI - [The use of rapid direct methods for identifying Streptococcus group A in medical practice]. PMID- 2251902 TI - Fibre-type composition, structure and cytoskeletal protein location of fibres in anterior tibial muscle. Comparison between young adults and physically active aged humans. AB - Muscle biopsies were obtained from the anterior tibial muscle (TA) of 15 healthy, sedentary young (23-37 years) and 13 healthy and physically active elderly (66-77 years) volunteers. The mean frequency of type I fibres was lower in the young subjects compared with the elderly, but the mean type I fibre cross-sectional area was equal in the two groups. The type IIA fibres were, however, smaller in the elderly than in young subjects. Capillary density, capillary per fibre ratio, capillaries in contact with type I fibres (CC) and CC in relation to type I and type II fibre area did not differ in the two groups. The number of capillaries in contact with type IIA fibres was higher in the younger group. Only occasional and minor pathological changes were observed in the young subjects. In the elderly, such changes were much more common, including central nuclei, ring fibres, fibre splitting, scattered highly atrophic fibres, moth-eaten fibres and vacuoles. Ring fibres were most easily identified with anti-desmin labelling and highly atrophic fibres exhibited a rough network of labelling. Increased content of actin and spectrin was also observed at the periphery of ring fibres. In the elderly group, a qualitative ultrastructural analysis was also obtained and obvious changes included some myofilament loss, collections of lipofuscin which were also observed in satellite cells, proliferation of the SR-T systems and increased wrinkling of nuclear membranes and sarcolemma. PMID- 2251903 TI - Distribution of neuropeptide Y-like immunoreactivity in the normoganglionic and aganglionic segments of human colon. AB - The localisation and distribution of neuropeptide Y (NPY)-like immunoreactivity were studied by use of immunohistochemical methods in gut tissues from 19 patients with Hirschsprung's disease, including 4 cases of long segment aganglionosis. In the normoganglionic segment, immunoreactive cell bodies and nonvaricose processes were seen within both myenteric and submucous plexuses. A scarce supply of varicose fibres was found in the lamina propria mucosae, muscularis mucosae and longitudinal muscle layer. NPY fibres were more frequently encountered in the circular muscle layer, although with a weakly immunostaining intensity. In addition, blood vessels in the submucosal connective tissue were surrounded by a typical plexus of varicose, NPY-positive fibres. Immunoreactive endocrine cells could be detected in the colonic epithelium. In the aganglionic segment, numerous nerve fasciculi comprising a small to moderate number of NPY fibres with varicosities were observed throughout the entire layer of the colonic wall. A few varicose, NPY-positive fibres were also contained in the relatively large, hypertrophic nerve fasciculi located in the intermuscular zone and submucosal connective tissue. NPY-immunoreactive fasciculi were more densely distributed in the distal aganglionic segment than in the proximal aganglionic one. On the other hand, the distribution of NPY-positive fibres in long segment aganglionosis was quite different from that in short segment type; in cases of long segment type, no immunoreactive nerve fibres were detected within the circular muscle layer of the proximal aganglionic segment near the oligoganglionic segment and only a few fibres were observed within the hypertrophic nerve bundle of the intermuscular zone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251904 TI - Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia. AB - Cases of old-aged demented individuals exhibited abundant cortical amyloid deposits but only small numbers of neurofibrillary changes. Neuritic plaques were rare or absent. Neither Ammon's horn nor isocortex revealed sufficiently large numbers of tangles to permit the diagnosis of fully developed Alzheimer's disease. Dense accumulations of neurofibrillary tangles and neuropil threads occurred only in layer Pre-alpha (II) of the entorhinal region. This pattern of cortical destruction may represent a variant of Alzheimer's disease or an initial stage of this disorder. PMID- 2251905 TI - Ultrastructural investigation of the CA1 region of the hippocampus after transient cerebral ischemia in gerbils. AB - Ultrastructural damage leading to delayed neuronal death was investigated in the mid-CA1 region of the hippocampus from the stratum (str.) moleculare to oriens after transient bilateral forebrain ischemia in Mongolian gerbils. After ischemia for 5 min without recirculation, mild swelling of the peripheral part of the apical and basal dendrites was already apparent in the str. moleculare and str. oriens. Mitochondria in the dendrites were also swollen in the same area. During recirculation for 12 h to 3 days, swelling of the dendritic cytoplasm persisted with formation of microvacuoles, but swelling of mitochondria receded. Microvacuolation and loss of microtubules were also observed in the proximal part of the dendrites during this period, and swelling and disruption of internal cristae were observed in mitochondria after recirculation for 3 days. The dendrites became severely degenerated after recirculation for 4 days. In the pyramidal cell bodies, no abnormality was observed at the end of ischemia for 5 min, but disaggregation of polyribosomes and swelling of the endoplasmic reticulum were observed 12 h after recirculation. Proliferation of the endoplasmic reticulum in parallel arrays occurred after recirculation for 1 day and persisted. Severe degeneration of the pyramidal cell bodies was obvious after recirculation for 4 days. The findings observed in the present investigation suggested that the neuronal structure most vulnerable to ischemia was the peripheral part of the dendrites and postischemic neuronal damage occurred early in this part of the dendrites. PMID- 2251906 TI - Microglia in cerebellar plaques in Alzheimer's disease. AB - Cerebellar amyloid deposits in Alzheimer's disease were studied by immunocytochemistry and with a series of antibodies that recognize human microglia, including anti-HLA-DR, LN-1, Leu-M5 and leukocyte common antigen. Microglia formed a dense reticular array throughout the cerebellum in areas with and without amyloid deposits. In areas with compact and reticular amyloid deposits, microglia had morphological features consistent with activation, such as cytoplasmic swelling and shortening and thickening of cell processes. In areas with diffuse amyloid deposits, microglia had delicate and highly ramified processes. Nevertheless, microglial cells or their processes were detected in association with amyloid deposits of all morphological types. These results raise the possibility that microglia may play a fundamental role in the pathogenesis of amyloid deposition in the cerebellum in Alzheimer's disease. PMID- 2251907 TI - Differential vulnerability of microtubule components in cerebral ischemia. AB - Differential vulnerability of the major components of microtubules was examined in ischemic gerbil brains by a light microscopic, immunohistochemical method using monoclonal antibodies for microtubule-associated protein (MAP) 1A and MAP2, polyclonal antibody for MAP1 and 2 as well as monoclonal antibody for alpha tubulin. Progressive cerebral ischemia during unilateral carotid occlusion for 5, 15 and 120 min and reperfusion for 3, 12 and 48 h following bilateral carotid occlusion for 10 min were studied. Ischemic lesions in the subiculum-CA1 region were visualized by all antibodies after ischemia for 5 min but the antibody for alpha-tubulin was less sensitive. The antibody for alpha-tubulin was also less sensitive than antibodies for MAPs for detection of early postischemic lesions. Differential sensitivity was also observed in the cerebral cortex and other brain regions. Microtubules in myelinated axons were more stable than those in dendrites. The observed loss of immunohistochemical reactivities for MAPs and alpha-tubulin may have been caused by activation of calcium-dependent proteolytic enzymes such as calpains. The discrepancy between MAPs and alpha-tubulin could be due to differences in affinities or topographic distributions of these proteins within microtubules. PMID- 2251908 TI - Morphology and neurophysiology of focal axonal injury experimentally induced in the guinea pig optic nerve. AB - A new model of focal axonal injury was reproduced by rapid and controlled elongation (uniaxial stretch) of the guinea pig optic nerve. Light microscopy study of optic nerve specimens after horseradish peroxidase injection into the vitreous of the animal's eye showed that axonal lesions were identical to those seen in human and primate post-traumatic diffuse axonal injury (DAI). The lesions were characterized by the formation of terminal clubs in severed axons and focal axonal enlargements in those axons that were lesioned-in-continuity. Visual evoked potentials upon flash stimulation were recorded before and after injury. Mean amplitude and mean latency of occipital peaks were significantly elongated in the acute post-traumatic phase. Electron microscopy examination showed that the main axonal changes observed in this model were cytoskeleton disorganization, accumulation of axoplasm membrane-bound bodies at the site of terminal balls and dilatations-in-continuity and detachment of the axolemma from the myelin sheath. Such axonal alterations were similar to those found in many other biological models of central and peripheral axonal injuries in which the lesion was produced by invasive methods. This model is unique since it reproduces the same mechanism of injury and the identical lesions that have been demonstrated in humans and primates with post-traumatic (DAI). PMID- 2251910 TI - Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells. AB - We have developed a functional vegetative model by an 18-min clamping of the ascending aorta combined with a bypass formation between the aorta to right atrium and the aorta to femoral vein. Complete global brain ischemia (CGBI) induced for 18 min with this model provided the following distinct advantages: cardiopulmonary functions were well preserved during postischemic recirculation, and all dogs survived without serious extracerebral complications. Neuronal damage in vegetative dog induced by an 18-min CGBI was studied by light and electron microscopy. The Purkinje cells and the hippocampal CA1 pyramidal cells showing clumping of nuclear chromatin and slightly increased stainability were observed after CGBI without recirculation. All these neurons showed transient increased stainability with microvacuolation 15 min after recirculation. Over 50% of these neurons showed virtually normal features 1 h after recirculation. Damage to these neurons progressed again slowly up to 6 h after recirculation. However, all these neurons had disintegrated 2-3 days after recirculation. A decrease in synaptic vesicles was observed in many presynaptic terminals in the molecular layers of the cerebellum after CGBI without recirculation. These changes in the presynaptic terminals progressed 15 min after recirculation. These results indicated that the damage to the Purkinje cells and the CA1 pyramidal cells induced by CGBI consisted of two phases, and that the change in the early phase was reversible. We speculate that the damage to the Purkinje cells in the early stage is related to the decrease of the synaptic vesicles in the presynaptic terminals. PMID- 2251909 TI - Targeting of adoptively transferred experimental allergic encephalitis lesion at the sites of wallerian degeneration. AB - To clarify the implication of the major histocompatibility complex class II (Ia) antigen induction in microglia following Wallerian degeneration in the central nervous system (CNS), experimental allergic encephalitis (EAE) was adoptively transferred to Lewis rats in which Ia antigens had been induced in microglia at the sites of Wallerian degeneration. In addition to randomly distributed typical EAE lesions, the recipient rats developed distinct inflammatory lesions in accord with the distribution of Ia-positive microglia; i.e., in the ipsilateral thalamus after cortical cryoinjury, and in the ipsilateral optic nerve, the contralateral optic tract and superior colliculus after unilateral eye ball enucleation. Thus, the EAE locus may be targeted by this approach. The inflammatory response was inducible by transfer of myelin basic protein-stimulated lymphocytes but not by transfer of phytohemagglutinin-stimulated or non-stimulated lymphocytes. When examined using monoclonal antibody surface markers; OX-6 for Ia antigen, W3/13 for pan T lymphocyte and OX-8 for cytotoxic/suppresser T lymphocyte, the types of lymphocytes in these lesions did not differ from those in ordinary EAE lesions in the spinal cord. The potential role of non-immunologically induced Ia-positive cell clusters that serve as a target for autoimmune CNS diseases was discussed. PMID- 2251911 TI - The human pineal gland in aging and Alzheimer's disease: patterns of cytoskeletal antigen immunoreactivity. AB - Patients with Alzheimer's disease (AD) and some aged controls may have diminished functions of the pineal gland. In this immunocytochemical study, we stained pineal glands from cases of AD and young and aged controls for cytoskeletal elements and amyloid. We found no evidence of neurofibrillary tangles (NFT) or the accumulation of neurofilaments, tau, A68, or beta/A4 amyloid deposition in pinealocytes or associated structures in cases of AD or controls. In both AD and controls, we observed dense immunoreactivity for phosphorylated neurofilaments in marginal plexuses associated with processes of pinealocytes, boutons, and knob like endings. The accumulation of phosphorylated neurofilaments in the processes of pinealocytes appears to be a normal morphological characteristic of the pineal gland and may not represent a pathological change. PMID- 2251912 TI - Neuropathology in Kearns-Sayre syndrome. AB - The neuropathological changes found at autopsy in a case of Kearns-Sayre syndrome are described. We have previously analyzed the respiratory chain function in isolated muscle mitochondria and also described a large deletion of muscle mitochondrial DNA (mtDNA) in this case. The neuropathological examination revealed prominent neuronal degeneration and gliosis of the basal ganglia and there were bilateral areas of softening and total loss of nerve cells in the lenticular nuclei. The pallidum and caudate nucleus disclosed accumulation of iron-containing pigment. The white matter in the cerebrum, brain stem and cerebellum showed widespread and focally accentuated spongy change due to splitting of myelin lamellae. It is suggested that deficiency of respiratory chain enzymes due to the mtDNA deletion is of pathogenetic importance in the development of the described changes. PMID- 2251913 TI - Polyglucosan bodies in sural nerve biopsies. AB - The presence of polyglucosan bodies in sural nerves collected over a 16-year period was studied in relation to age, sex, presence of polyneuropathy, and concomitant presence of central nervous system disorder. Polyglucosan bodies have been seen in only one patient without a polyneuropathy. This patient was suffering from Lafora's disease. In all other sural nerves positive for polyglucosan bodies a polyneuropathy was present. Within this group the prevalence of polyglucosan bodies was positively correlated with age, and if a central nervous system disorder was associated, this prevalence was more distinct. With semiquantitative measurements of the surface of polyglucosan bodies a significant correlation was found between age and percentage of large bodies. PMID- 2251914 TI - Lewy bodies in the lower sacral parasympathetic neurons of a patient with Parkinson's disease. AB - Lewy bodies were observed incidentally in the neurons of the dorsal group of nucleus intermediolateralis of the 3rd sacral segment of the spinal cord in a 74 year-old male with Parkinson's disease. The findings indicate the degeneration of the preganglionic parasympathetic neurons innervating the internal anal sphincter. The correlation between the findings and the mechanism of constipation in this disease are discussed. PMID- 2251915 TI - Selective sparing of Betz cells in primary motor area in hypoxic-ischemic encephalopathy. AB - Two cases of postoperative hypoxic-ischemic encephalopathy are described in which Betz cells of the primary motor area were selectively spared. In one patient the hypoxic-ischemic encephalopathy led to a vegetative state and in the other patient to a spastic quadriparesis and cortical blindness. In contrast to the relative sparing of Betz cells, Purkinje cells of the cerebellar cortex were totally destroyed. These two cases suggest that Betz cells are relatively resistant to hypoxic-ischemic insult under certain conditions. PMID- 2251916 TI - Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis. AB - Recent observations have delineated the neurological manifestations of Lyme disease, but, to our knowledge, no detailed neuropathological study from autopsy cases has been reported. In this report we describe the neuropathological findings in a case of Lyme neuroborreliosis. The chronic meningitis, the occlusive meningovascular and secondary parenchymal changes that we found are similar to those occurring in the meningovascular form of neurosyphilis. Thus, we suggest that the case described here represents the meningovascular form of tertiary Lyme neuroborreliosis. PMID- 2251917 TI - Sarcomatous proliferation of the vasculature in a subependymoma: a follow-up study of sarcomatous dedifferentiation. PMID- 2251918 TI - Placement and longevity of amalgam restorations in Denmark. AB - A survey has been made of the reasons for placement of 4932 amalgam restorations in Denmark. In patients more than 16 years of age 39% of all restorations were made because of primary caries, and 61% were replacements of failed restorations. In children 74% of the restorations in primary teeth and 84% of those in permanent teeth were inserted because of primary caries. The reasons for replacement of restorations depended on dentition, age of the patient, and type of restoration. Secondary caries was the most frequent reason for replacement of failed restorations in permanent teeth and accounted for 38% of all failures. Marginal discrepancies and bulk fracture of fillings were the other two major reasons. In primary teeth fracture and loss of fillings were the commonest reasons, whereas secondary caries accounted for only a quarter of all restorations replaced. The age of the restorations replaced ranged from 0 to 46 years, and half of the failed restorations in permanent teeth of adults were more than 8 years old. A shorter longevity of failed restorations was noted in primary teeth and permanent teeth of children. PMID- 2251919 TI - Placement and longevity of tooth-colored restorations in Denmark. AB - A survey has been made of the use of materials and the reasons for placement of 2542 tooth-colored restorations in Denmark. In adults 38% of all the restorations were inserted because of primary caries, and 62% were replacements of failed restorations. In children primary caries was the reason for placing 68% of the restorations in deciduous teeth and 77% of those in permanent teeth. Resin-based materials were the most frequently used tooth-colored restorative, except in the treatment of deciduous teeth, for which glass ionomer cement was used preferentially. Silicate cement was used for less than 2% of the tooth-colored restorations, and the few old silicate cement restorations were most often replaced with resin materials. The reasons for replacement of resin restorations were dependent on dentition, age of the patient, and type of restoration. Secondary caries, fracture of restoration, and loss of fillings were the most frequently recorded failures. The age of the resin restorations replaced ranged from 0 to 19 years, and half of the failed restorations in adults were more than 6 years old. In permanent teeth in children half of the failed resin restorations were replaced within 2 years, whereas half of those in primary teeth were replaced within 1 year. PMID- 2251920 TI - Invasive growth of Actinobacillus actinomycetemcomitans on solid medium (TSBV). AB - When grown on agar, most Actinobacillus actinomycetemcomitans form circular and convex colonies with an internal star-shaped morphology. Such colonies adhere firmly to the agar, and when removed, a star-shaped imprint similar to that of the intact colony remains. This study was undertaken to determine the nature of this in vitro growth. Stereo-microscopy and scanning and transmission electron microscopy showed that the star-shaped imprint of A. actinomycetemcomitans colonies reflected pseudopod-like extensions of the bacterial colony which penetrated deep into the TSBV agar. The center of the colonies consisted primarily of ghost-like cells, while the dense border of each colony, including the pseudopods, expressed characteristics of vital cells. The latter were embedded in vast amounts of extracellular vesicles, and the outer aspect of the pseudopods was lined with a border of such vesicles. PMID- 2251921 TI - A 3-year clinical study of alternatives to high noble dental casting alloys type 3. AB - For the purpose of evaluating the quality of dental casting alloys, 22 patients were recalled for clinical examination 3 years after insertion of crowns and bridges made from the low-gold alloy Midas and the silver-palladium alloy Albacast. A high-gold alloy, JS C, served as a reference alloy. The examination included registrations of tarnish, plaque index, gingival index, and margin index. In addition, the California Dental Association's quality evaluation of dental care was used by two independent calibrated examiners. From the results of the present study it can be concluded that the crowns made from the alloy Midas in the annealed condition and the alloy Albacast are well suited for clinical use. Some tarnish appeared, but this may occur intermittently. PMID- 2251923 TI - Effect of polyacrylic acid treatment of dentin on adhesion of glass ionomer cement. AB - This investigation measured the effect of polyacrylic acid treatment of dentin on adhesion of glass ionomer cement. The dentin was ground on paper no. 220 or no. 500 and treated with a polyacrylic acid solution of 10% or 25% for either 10 or 30 sec. The differences observed in the scanning electron microscope between the differently treated dentin surfaces were not reflected in the bond strength results. Only variations in surface texture due to different coarseness of grinding influenced the adhesion. For specimens ground on paper no. 220, pretreatment with polyacrylic acid enhanced adhesion of glass ionomer cement. Polyacrylic acid had no effect on bonding between glass ionomer cement and dentin ground on paper no. 500. PMID- 2251922 TI - Non-specific esterases in partly mineralized bovine enamel. AB - Activity for non-specific esterase was demonstrated in the matrix of developing bovine enamel with alpha-naphthyl acetate and 5-bromoindoxyl acetate as the esterase substrates. By use of high-performance liquid chromatography gel filtration, ion-exchange chromatography, and electrophoresis three esterases were shown to be present in the enamel matrix. The enzymes showed highest activity at pH 6.5-7.5. In sections a strong reaction was observed in the secretory ameloblasts. The esterases may be proteolytic enzymes that participate in the degradation of the matrix proteins. PMID- 2251924 TI - An individual tooth wear index and an analysis of factors correlated to incisal and occlusal wear in an adult Swedish population. AB - The aim of the study was to introduce an individual tooth wear index and to use this index to investigate factors correlated to occlusal wear. The material consisted of 585 randomly selected dentate individuals from the community of Jonkoping, Sweden, who in 1983 reached the age of 20, 30, 40, 50, 60, 70, or 80 years. The degree of incisal and occlusal wear was evaluated for each single tooth in accordance with criteria presented earlier. An individual tooth wear index, which made it possible to rank individuals in accordance with incisal and occlusal wear, was used as dependent variable to investigate factors related to incisal and occlusal wear. Of all factors analyzed, the following were found to correlate significantly with increased incisal and occlusal wear: number of existing teeth, age, sex, occurrence of bruxism, use of snuff, and saliva buffer capacity. Stepwise multiple regression analysis gave a total explanation factor of R2 = 0.41. It was also possible to distinguish well between groups of individuals with and without tooth wear by means of these factors. PMID- 2251925 TI - An in vivo study of glass ceramic (Dicor) inlays. Preliminary report. AB - For the purpose of evaluating the clinical quality of glass ceramic (Dicor) inlays 15 patients with 37 inlays were examined 1 to 22 months after placement. In addition to certain periodontal variables, the inlays were rated by two independent examiners using the California Dental Association (CDA) quality evaluation system. The results of the present study showed that dental plaque was seen less often on proximal surfaces with inlays than on homologous proximal surfaces. Three patients reported hypersensitivity of the dental pulp. The examination using the CDA criteria showed that 54% of the inlays had a slight color mismatch, and slightly roughened surfaces were occasionally seen (35.5%). In nearly 30% of the inlays there was visible evidence of ditching along the margins. At present, no judgement can be made about the longevity of ceramic inlays. PMID- 2251926 TI - Posture in otoneurology. Volume I. AB - In this study, posture is studied in the context of neuro-otological problems. In the several chapters, postural elements, postural influence upon balance aspects as well as postural components of the balance function in normal and pathological conditions are emphasized. Two main applications are put forward: rehabilitation by postural treatment techniques (REHAB) and examination techniques for the vestibulospinal aspects (posturography--PG). I. Balance function Balance is provided by automatic reflexes for stabilization of the visual field (vestibulo ocular reflex--VOR) and for a correct posture, erect standing (vestibulo-spinal reflex--VSR) and head position (vestibulo-collic reflex--VCR). The fundamental characteristics of these reflexes are described, especially of those related to posture. The reflexes are elaborated on the basis of sensory inputs that inform about changed relations to space and environment, provided by visual, vestibular and proprioceptive systems. The sensory signals are further processed by the centers to adequate reflexes and to some extent to a conscious awareness. II. Dysfunction and adaptation Dysfunction in the balance mechanisms leads to erroneous reflexes, but most importantly to frightening sensations of vertigo. The peripheral disturbances produce a sensory mismatch which is the primum movens of vertigo. Built-in adaptive mechanisms cope with this disturbance and restore global balance function. The mechanisms involved have been studied as vestibular compensation and habituation, VOR-reflex plasticity and sensory "substitutive" compensation. The mechanisms are set into action by the dysfunctional situation and constitute an error-controlled process. Emphasis is laid upon the items related to rehabilitation treatment and posturography. A survey of clinical entities of vestibular peripheral dysfunction is included. III. Examination techniques The logical approach to the patient with vertigo consists in an analysis of the complaints pattern, correlation of it with the dysfunctional state revealed by clinical observation, and functional tests of balance. Correct interpretation of the test results is a pre-requisite. Postural aspects of these examination techniques, especially posturography, are put into evidence in this review. The strategy used in the department is sketched. IV. Contribution of the examination techniques: functional evaluation results The several data obtained by each examination technique are discussed within the scope of the experiences in the department. Data from the literature and from personal experience, especially interpreted in the context of rehabilitation and posturography, are analysed. V. Reh PMID- 2251927 TI - Posture in otoneurology. Volume II. PMID- 2251928 TI - Selective response activation can begin before stimulus recognition is complete: a psychophysiological and error analysis of continuous flow. AB - In discussions of process models of human information processing, the continuous flow conception (Eriksen and Schultz 1979) plays a prominent role. A central prediction of this conception is that any information in a display associated with a response activates that response as soon as it becomes available in the perceptual system. If it concerns the correct response channel, then response facilitation occurs. If it concerns the incorrect response channel, then response competition occurs. To assess these mechanisms more directly, we used psychophysiological measures as well as reaction time (RT). We used the latency of the P3 component of the event related brain potential (ERP) as an index of stimulus evaluation duration, the onset of lateralized motor activity derived from the ERP as an index of selective central motor activation, and the onset of electromyographic activity as an index of the start of peripheral motor activation. Subjects were required to respond to target letters that were either flanked by letters that signalled the opposite response (incompatible arrays), by the target itself (compatible arrays), by letters not associated with a response (neutral arrays), or by no other letters (targets alone). Our results replicated the basic findings obtained in this paradigm. RTs to targets alone did not differ from RTs to compatible arrays. The latter were faster than RTs to neutral arrays, which were faster than RTs to incompatible arrays. P3 latencies were longer on incompatible than on neutral trials, and longer on compatible than on target alone trials. Incorrect central response activation on incompatible trials and correct central response activation on compatible trials, both began earlier than on target alone trials. Peripheral responding on both trial types, however, began later than on target alone trials. More incompatible but less compatible trials than neutral ones exhibited incorrect peripheral response activation. Peripheral response execution was faster and more accurate on compatible than on target alone trials, while it was slower and less accurate on incompatible than on neutral trials. These results indicate, that the flankers activated their associated response channel while display evaluation was still going on, and that response facilitation and competition occurred. After applying criteria proposed by Miller (1988), it was concluded that the set of stimulus recognition processes and the set of response activation processes cannot be regarded as independent stages of processing. PMID- 2251929 TI - Internal and external control: a two-factor model of amplitude change of event related potentials. AB - The present paper critically examines the contributions of Event-Related Potential (ERP) measures in mental chronometry research. It is argued that amplitude variations in ERP components may provide valuable information regarding the intensity and timing of information processes, and that these amplitude changes are related to energetical rather than to computational processes. It is also suggested that amplitude variations of ERP components in visual discrimination and selective attention tasks are caused by two different processing modes, denoted as external and internal control that are associated with different neural structures. It is further assumed that these two control systems converge upon thalamic neurons that regulate the sensory input to cortex, and that the direction of sustained ERP amplitude changes reflects which system is dominant. Recent ERP studies have shown that the effects of task variables related to motor control are manifested in a surprisingly early phase of the ERP waveform, and that these effects overlap in time with the effects of task variables related to input control. These findings suggest that at least in visual discrimination and selective attention tasks external and internal modes of processing may be activated in parallel. PMID- 2251930 TI - Phonological and motoric demands in handwriting: evidence for discrete transmission of information. AB - In an experiment with handwriting tasks effects of phonological and motoric task factors upon reaction time and movement time were measured to test implications of a discrete information processing account of the task. The model is built up of serially organized stages, each of which monitors one specific type of operation, necessary to generate a message. The serial structure of the model is defined as the limitation that higher levels of the model provide their output to the next lower processor in the hierarchy, and receive their input from the next higher stage. The parallel character of the model is exemplified through the assumption that all processors are active at the same time and concurrently with the real time production of writing movements. The study adds evidence that a serial architecture of processors can be compatible with the parallel processing of a message as long as more abstract operations are prepared more in advance to real-time movements than operations lower in the hierarchy. In the experiment the prediction was tested that the time course of the manifestation of phonological and motoric task demands reflects the discrete and serial structure of the model. PMID- 2251931 TI - Additive factor method applied to psychopathology with special reference to childhood hyperactivity. AB - A review is made of available studies using the Additive Factor Method (AFM) in clinical research. The paper argues that by using the AFM in studies of psychological dysfunctioning a major contribution can be made: first, in preventing spurious findings, second, distinguishing between group differences with and without information processing deficits, and third, by identifying fundamental processes which may be impaired. This may offer psychodiagnostics an empirical basis on which to define disorders. This paper reviews studies contributing to this endeavour. It further raises the question of how to interpret clinical research, which is conducted in the tradition of information processing but not within the frame of reference of the AFM. It is suggested that such research is useful and complementary to that conducted using the AFM. Further, it is suggested that the role of energetical factors in clinical disorders and in their treatment is an important area for future experimental clinical research. PMID- 2251932 TI - Discreteness and continuity in models of human information processing. PMID- 2251933 TI - Plastic and trophic effects of amino acid transmitters in the developing nervous system. PMID- 2251934 TI - Glia protect hippocampal neurons against excitatory amino acid-induced degeneration: involvement of fibroblast growth factor. AB - Low density cell cultures of embryonic rat hippocampus containing astrocyte-like glia and neurons were used to test the hypothesis that glia can alter 'natural' and excitatory amino acid (EAA)-induced neuronal death. Neurons contacting glia survived for longer time periods than did neurons not contacting glia. Neurons associated with glia were also protected against glutamate and kainate neurotoxicity. Fibroblast growth factor (FGF)-like immunoreactivity was associated with the glia. Addition to the cultures of an antiserum raised against an internal peptide fragment of FGF greatly reduced the protective effect of glia against both spontaneous and EAA-induced neurotoxicity. Contact with glia, or exposure to exogenous FGF, also protected the hippocampal neurons against Ca2+ ionophore-induced degeneration indicating that FGF enhanced the ability of neurons to handle a Ca2+ load. Taken together, these results suggest that glia surface-associated FGF may play important roles in hippocampal development, and in neurodegenerative conditions that involve EAAs. PMID- 2251935 TI - Kainic acid lesioning alters development of the outer plexiform layer in neonatal rabbit retina. AB - The first synaptic relay in the primary visual pathway occurs between terminals of photoreceptors and second-order neurons within the outer plexiform layer of the retina. During development, one of these types of second-order neurons, the type A horizontal cell, differentiates and assumes mature characteristics several days before any other cells ramifying in that synaptic layer. In neonates, horizontal cells appear to be GABAergic during the first 5 days of postnatal life and in addition they also are responsive to kainic acid. We have previously suggested that they may play a pioneering role in the postnatal development of the outer plexiform layer, perhaps providing structural guidance or trophic substances such as GABA, for synaptic development. To test this hypothesis, we first demonstrated that a single intraocular injection of kainic acid within 24 hr of birth results in a permanent and selective loss of type A horizontal cells in the outer retina. Retinas from animals maintained for 5 days postinjection were harvested for analysis of postnatal development of the outer plexiform layer in the absence of horizontal cells. One of the major findings was that kainic acid treatment caused a reversal of the normal complement of photoreceptor cell types, resulting in an abnormally high rod/cone ratio. The distribution of cell processes within the outer plexiform layer was also altered and normal synaptic connections were not made. In spite of these changes in the constituents of the outer plexiform layer, the normal position of the synaptic layer was not affected by the loss of horizontal cells. These results rule out the possibility that horizontal cells provide a structural barrier which is an absolute requirement for establishing the location of the outer plexiform layer. Rather, these cells may be more involved in cell differentiation and synaptogenesis. PMID- 2251936 TI - Taurine-induced neuronal differentiation: the influence of calcium and the ganglioside GM1. AB - Taurine-induced differentiation was examined in the murine neuroblastoma Neuro-2a cell line in the presence or absence of the monosialoganglioside GM1 and under conditions in which Ca2+ levels were manipulated. Taurine (4 mM), GM1 (200 micrograms/ml), or taurine with GM1 were applied to culture media that contained either various concentrations of Ca2+ or the Ca2+ ionophore A23187. Taurine or GM1 and taurine with GM1 increased the number of cells emitting neurites above that found for controls. A significant interaction was found between treatment (taurine, GM1 or taurine + GM1) and the manipulations of Ca2+ levels, affecting the number of neurites and producing changes on the neuritic and perikaryal surfaces. Treatment with both taurine and taurine + GM1 and the various concentrations of Ca2+ resulted in a significant increase in neurite elongation. The Ca2+ ionophore A23187 in the presence of taurine or taurine + GM1 caused neurites to grow longer than observed in media containing Ca2+, either in a low concentration (about 125 microM) or at 1-2 mM. Taurine-treated cultures in the presence of extracellular Ca2+ or A23187 were characterized by surfaces with numerous microvillar, spine-like projections. This effect was enhanced with GM1 and was less pronounced in the medium containing low levels of Ca2+. Transmission electron microscopy of the taurine-stimulated neurons revealed an excessive number of clear-core vesicles (40-200 nm in diameter) in perikarya, neurites and neuritic varicosities and growth cones. In addition, numerous aggregates of intermediate filaments were seen. They were most abundant in the taurine + GM1 treated cultures. The taurine + A23187 cultures also exhibited numerous microtubules within the elongated processes. The different neuritic patterns induced by taurine under conditions in which Ca2+ levels were manipulated and/or when cells were exposed to exogenous GM1 suggest that taurine's actions depend in part on Ca2+ flux. PMID- 2251937 TI - Chemiluminescent reactions in the Belousov-Zhabotinskii oscillating system. AB - Chemiluminescence (CL) occurs during reactions of several of the components of the CH2 (COOH)2-KBrO3-MnSO4-H2SO4 self-sustained system. In contrast to the kinetics determined using potentiometry and spectrophotometry, the CL intensity kinetic curve during the oxidation of manganese (II) ions by acidic bromate has an extremum. Experimental dependences of the maximum CL intensity value on the initial reagent concentrations have been determined and compared with the results of the numerical simulation based on the commonly accepted Noyes-Field-Thompson mechanism. PMID- 2251939 TI - Bioluminescence and chemoluminescence literature. The 1983 literature: Part 1. PMID- 2251938 TI - Three-peaked chemiluminescent response of human peripheral blood leukocytes following stimulation with phytohaemagglutinin (PHA). AB - Luminol-enhanced chemiluminescence (CL) was used to examine the response of various leukocyte populations following stimulation with a crude extract of Phaseolus vulgaris, namely phytohaemagglutinin (PHA-C). Populations stimulated included a human peripheral mixed leukocyte preparation (MLP), and purified preparations of lymphocytes, monocytes and polymorphonuclear leukocytes (PMNL). Mouse peritoneal exudate cells and the lymphocytic cells lines Molt #4 and Daudi were also stimulated. Following stimulation, a characteristic three-peaked chemiluminescent response was obtained from the MLP population. Little or no response was obtained from the purified lymphocytes. Monocytes produced a sharp peak corresponding to the second peak of the MLP response and PMNL produced a broad peak corresponding to the third peak of the MLP response. Mouse peritoneal exudate cells containing lymphocytes and monocytes/macrophages showed a two peaked stimulation which corresponded to the first two peaks of the MLP response. Molt #4 and Daudi showed no chemiluminescence if stimulated individually, but if added to a MLP substantial enhancement of the first and second peaks was observed. These results indicate some form of lymphocyte/monocyte interaction leading to enhanced CL following PHA-C stimulation. PMID- 2251940 TI - Different types of postoperative diabetes insipidus and the relation to basal and stimulated serum prolactin levels in patients with hypothalamo-hypophyseal tumorous lesions. AB - To evaluate the interrelationships between anterior pituitary function and the antidiuretic system in patients harbouring hypothalamo-hypophyseal tumorous lesions, combined anterior pituitary stimulation tests were performed in the pre (n = 192 patients) and postoperative (n = 151 patients) state. Basal and stimulated plasma antidiuretic hormone, serum as well as urinary osmolality and diuresis were analyzed to determine the residual functional capacity of the antidiuretic system. In 106 patients with non-prolactin (PRL) secreting tumours basal and stimulated PRL secretion of the residual anterior pituitary was studied pre- and postoperatively. It was found that in the preoperative state latent (n = 12 patients) or manifest (n = 10 patients) types of diabetes insipidus (DI) were related to a significant decrease of maximal stimulated levels of thyroid stimulating hormone as well as basal and maximal stimulated levels of follicle stimulating hormone relative to patients without DI. In the postoperative state DI lasting longer than 10 days (n = 51 patients) was associated with decreased basal and maximal stimulated concentrations of cortisol, luteinizing and follicle stimulating hormone, whereas basal and maximal stimulated levels of PRL were significantly increased compared to those patients without DI (n = 61 patients). Decompression (n = 65 procedures) via the transnasal route was related with a lower frequency of the more severe types of DI (n = 7 patients) and a significant decrease of basal and maximal PRL levels in patients with non-PRL secreting tumours. The transcranial approach (n = 86 procedures) caused a higher rate of severe DI types (n = 33 patients) and an increase of PRL secretion from the residual anterior pituitary lobe. Patients without DI or DI of mild severity (n = 50), as a group, had a significant decrease of basal and maximal PRL levels compared with preoperative values (preoperative: basal = 14.3 +/- 1.5 ng/ml, max = 31.4 +/- 1.5 ng/ml, postoperative: basal = 9.6 +/- 1.1 ng/ml, max = 24.9 +/- 2.9 ng/ml). In patients with severer degrees of DI (n = 40) PRL levels were significantly increased, respectively (preoperative: basal = 15.3 +/- 3.1 ng/ml, max = 23.9 +/- 7.6 ng/ml, postoperative: basal = 19.7 +/- 3.4 ng/ml, max = 38.6 +/- 7.9 ng/ml). It was concluded that in the surgical treatment of non-PRL secreting hypothalamo-hypophyseal lesions the results of early postoperative assessment of basal and stimulated PRL levels may predict the type of postoperative DI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2251941 TI - Rebound of ICP after brain compression. An MRI study in dogs. AB - The rebound of intracranial pressure (ICP) occurring after decompression of an intracranial mass lesion was studied in an epidural balloon compression model. Intracranial morphology and brain tissue water content were assessed with magnetic resonance imaging (MRI). Fast and slow components of the transverse relaxation time (T2) were used as indicators of brain oedema development. During balloon compression a progressive prolongation of both the fast and the slow T2 components took place. Following deflation of the balloon both components increased rapidly, particularly the slow-T2. The MR scans displayed progressive occlusion of the aqueduct, and obliteration of the ambient and pontine cisterns. The changes in morphology and in water content after decompression had largely the same time course as the development of the rebound of ICP. In contrast, no changes in morphology and tissue water content occurred after hydrostatic brain compression achieved by subarachnoid fluid infusion. The findings suggest that the intracranial pressure rebound is caused by cerebral oedema accumulated during and particularly in the recirculation phase after an ischaemic injury of adequate intensity and adequate duration. PMID- 2251942 TI - A new haemodynamic factor in cerebral AVM. Aspiration from the venous system demonstrated in two cases of pedonculo-Galen AVM successfully cured by occlusion of the superior longitudinal sinus. AB - Using a Doppler Mark 500 of ATL we measured the systolic and diastolic velocity of the red cells into the main arteries of the neck (diastolic rate cm/sec) thus approaching the flow in two cases of upper brain stem AVM with a unique drainage into the superior longitudinal sinus through an enlarged vein of Galen and a falcine sinus. Because of the desperate clinical condition of the children it was decided to stop the high blood flow by closing the aspiration coming from the low pressure of the venous system above and below the site of union between the malformation and the superior longitudinal sinus. An intra-operative and post operative measurement of the diastolic rate showed a radical effect of the closure of the superior longitudinal sinus. The demonstration of this aspirative factor has allowed us to classify an AVM as a haemodynamic push-pull malformation. PMID- 2251943 TI - Hypoglossal neuroma following excision of a huge recurrent acoustic neuroma and facio-hypoglossal anastomosis. A complex management problem. AB - A case of neuroma of the intracranial part of the hypoglossal nerve, not associated with neurofibromatosis, is presented. The patient had previously undergone surgery for the removal of a contralateral acoustic neuroma, and subsequent facio-hypoglossal anastomosis. The importance of early diagnosis, pre operative clinical assessment and post-operative care is stressed. PMID- 2251944 TI - Dynamic aspects of expanding cava septi pellucidi et Vergae. AB - Two paediatric patients with expanding cysts of the cava Vergae et septi pellucidi are presented. In the first patient, consecutive CT scans showed a growing cavum thought to be responsible for his dramatic increase in head circumference. In the other patient, the expanding cavum was discovered because a routine skull X-ray after minor head trauma revealed marked impressiones digitatae. Both patients were successfully treated with stereotactically placed internal shunts from the cysts via the lateral ventricle to the subarachnoid space. During this procedure, contrast medium was instilled, and the cysts were visualized on postoperative CT scans. Some dynamic aspects of such expanding cava are discussed. PMID- 2251945 TI - Large colloid cyst in lateral ventricle simulating brain tumour. Case report. AB - This case report describes a patient presenting with symptoms of increased intracranial pressure, whose computerized tomographic (CT) scan was highly suggestive of a large low-grade glioma invading the basal ganglia. Magnetic resonance imaging (MRI) revealed a well-demarcated space-occupying mass of increased intensity in the left lateral ventricle and adjacent white matter. Following stereotactic biopsy, which yielded a homogeneous jelly-like material, the mass was removed microsurgically and was found to be most like a colloid cyst on histological examination. Discussion focuses on the clinical and differential diagnostic implications of this very unusual combination of findings. PMID- 2251946 TI - New microsurgical suction tubes. AB - A set of new suitable microsurgical suction tubes has been designed especially suitable for fragile and delicate tissues such as the nervous and vascular tissues in the brain and spinal cord. The set provides two different shafts and five different tubes for superficial of deep micro- as well as macro-operations. These new suction tubes have two major advantages compared to traditional suction tubes. Firstly: the perforated smooth suction-tip allows continuous suction without damage to the tissue and secondly: the tubes are quickly and easily exchanged from the suction shaft when necessary. PMID- 2251947 TI - Fronto-temporal approach with orbito-zygomatic removal. Surgical anatomy. AB - Removal of the orbital rim and the zygomatic arch can be associated with fronto temporal craniotomy to gain additional space, so as to decrease cerebral retraction. In order to quantify the gain provided by this enlarged approach, the authors underwent anatomical studies comparing the field view angle of various intracranial targets with and without orbito-zygomatic removal, in 11 fresh human cadavers with the brain in situ. The field view angle was increased, thanks to orbito-zygomatic removal, on average, by 75% in the sub-frontal approach, 46% in the pterional approach, and 86% in the sub-temporal approach. Such approaches can be very useful for access to difficult lesions located in the vicinity of the skull base. In the last 3 years 21 patients were operated upon using this technique, with excellent results. PMID- 2251949 TI - Encephalo-duro-arterio-synangiosis in children with moyamoya disease. AB - Encephalo-duro-arterio-synangiosis (EDAS) was done in 16 Japanese children with Moyamoya disease on 22 sides. The results were evaluated clinically, angiographically, and by positron emission computed tomography (PET). Postoperative external carotid angiograms showed a good collateral circulation through EDAS in 72 percent of the treated sides. Two-thirds of the sides examined by PET showed improvement in cerebral blood circulation, particularly at the surgically-treated cortex. Postoperatively the symptoms disappeared in those with good new collateral formation. TIA, RIND, and/or involuntary movement disappeared in 31 percent and partially so in 44 percent 6 months after EDAS. The TIA in the lower limb and/or involuntary movement persisted in some children. This surgical approach seems applicable particularly for children with the ischaemic type of Moyamoya disease, however, the procedure also has drawbacks. Development of collateral circulation was insufficient in some cases, and the territories of the anterior cerebral artery (ACA) or posterior cerebral artery (PCA) were often not covered, even in those with a good new collateral formation in the middle cerebral arterial (MCA) area. PMID- 2251948 TI - Intraoperative ultrasound (US) imaging. Comparison of pathomorphological findings in US and CT. AB - Experience with the use of intraoperative ultrasound (US) imaging in over 300 patients are presented in this paper and discussed with special reference to various pathomorphologies as well as their identifiability within the brain/intracranium. In 201 of these patients, the pathomorphological peculiarities in US could be compared with preoperative CT findings. As a general result, all investigated lesions could be identified during intraoperative US investigations with the exception of small aneurysms. Most of the lesions gave at least partly higher echosignals than normal brain tissue, except arachnoid cysts. Size and shape of lesions were comparable in US and CT with the exception of some gliomas; in the latter group, the diffuse image in US was more akin to the situation likely to be found by the surgeon during operation, whereas CT used to give a misleading picture of a more or less clearly delineated tumour. US allowed more accurate differentiation between intratumoural necrosis and cysts than CT: the latter was misleading in many instances. At the present state of development, real time US imaging does not allow a histopathological diagnosis. The ease of handling and the high quality of morphological imaging, however, warrant a number of practical applications in daily neurosurgical practice. PMID- 2251951 TI - Neurocutaneous syndromes with pigmentary abnormalities and central nervous system involvement. II. Two cases with atypical incontinentia pigmenti. AB - Two cases are reported of a boy and a girl with similar neurocutaneous syndromes clinically characterized by hyperpigmented skin patches and severe CNS involvement. The diagnosis of atypical cases of Incontinentia Pigmenti is suggested. The different syndromes with mental and motor retardation associated with skin abnormalities (Incontinentia Pigmenti, Ito's hypomelanosis, phakomatoses, etc.) are reviewed. PMID- 2251950 TI - Exaggerated spontaneous release of tumor necrosis factor-alpha/cachectin in patients with migraine without aura. AB - Serum levels of tumor necrosis factor (TNF)-alpha/cachectin have been evaluated in 20 patients with Migraine without Aura (MwA) versus 17 patients with Chronic Type Tension Headache (CTTH). Results show an exaggerated release of TNF alpha/cachectin in sera of patients affected by MwA, while in CTTH patients TNF serum concentration is comparable to that observed in normal donors. Some hypotheses are formulated in order to clarify the TNF-alpha/cachectin spontaneous production and its biological significance in patients with MwA. PMID- 2251952 TI - The distal type of hereditary motor neuropathy. Clinical and neurophysiological report of a dominant case. PMID- 2251953 TI - Asymptomatic carotid bruit as related to single risk factors. A flowmetric study. AB - The prevalence of asymptomatic carotid bruit is 4 per cent in the general population aged over 40 years. According to most authors, it is an evident risk factor for stroke and myocardial infarction. In the present study the clinical data and Doppler flowmeter analysis of 5 groups of patients are reported. These patients had risk factors for cerebrovascular disease, without cerebral symptoms. An age matched group of healthy control subjects was also studied. The prevalence of haemodynamic stenosis (more than 50 per cent) of carotid artery is significantly higher among subjects with peripheral arteriopathy and arterial hypertension compared with other groups. On the other hand nonhaemodynamic stenosis (below 50 per cent) of carotid artery occurs to the same extent in patients and control groups. The possible implications of these findings on the knowledge of cerebrovascular obstructive disease are discussed. PMID- 2251954 TI - Epidemiology of Parkinson's disease in Italy. A descriptive survey in the U.S.L. of Cento, province of Ferrara, Emilia-Romagna. AB - In order to verify the epidemiology of Parkinson's disease in northern-Italy, we carried out a descriptive study in the Local Health Service No. 30 of Cento, Emilia-Romagna. Based on 73 accepted cases, the prevalence rate on December 31, 1987, was 190.3 per 100,000 population. No significant difference was reported between the two sexes. The highest rates were observed in the age groups over 60 years. Our data indicate that the risk of Parkinson's disease in northern-Italy is similar to that observed in other Caucasian populations. PMID- 2251955 TI - Subacute parkinsonism from a single lacunar infarct in the basal ganglia. AB - The authors describe the case of a patient showing a lateralized and subacute parkinsonism with CT-evidence of a single lacunar infarct in the contralateral basal ganglia. The vascular origin of this type of subacute parkinsonism is emphasized. PMID- 2251956 TI - Abnormalities of central motor conduction in asymptomatic HIV-positive patients. Significance and prognostic value. AB - Percutaneous magnetic stimulation of the brain and spinal cord is a technique developed to demonstrate early and subclinical abnormalities in corticomotoneuron pathways. Central motor conduction time (CMCT) was evaluated in 58 HIV seropositive patients neurologically asymptomatic (CDC groups II and III) and in two control groups. CMCT was abnormal in about 50% of HIV-seropositive patients. These electrophysiological abnormalities seem to have a negative prognostic value since about 64% of the patients with abnormal parameters seem to progress more rapidly to AIDS stages. PMID- 2251957 TI - A case of cryptococcal meningoencephalitis and focal cerebral vasculitis with transient immunodeficiency. AB - The AA. report a case of CNS cryptococcosis with vasculopathic complications in a woman in perfect physical conditions. The patient was admitted to hospital after complaining for 20 days of fever, headache and rachialgia. CSF examination revealed hypoglicorrachia (18 mg %), cells 440 mmc (polymorphonuclear leukocytes 90%), brain CT scan negative. During antimycobacterial treatment right hemiparesis appeared; brain CT: hypodense lesion in the posterior brachium of the left inner capsule; at its base the lesion showed a hypodense streak coherent with thromboembolic damage or deep vasculitis. OKT4 lymphocytes were 6% (absolute number: 70). The antimycotic treatment, following the positive reaction of the CSF culture to Cryptococcus Neoformans, entirely cured the hemiparesis and normalized the CSF while OKT4 lymphocytes rapidly grew. PMID- 2251958 TI - Multiple primary malignant tumours: gemistocytic astrocytoma with leptomeningeal spreading and papillary thyroid carcinoma. A case report. PMID- 2251959 TI - [Possible mechanisms of the action of drugs for hemicrania]. AB - Different classes of drugs are used in the pharmacological treatment of headache, both during migraine crisis and migraine prophylaxis. How these drugs exert their therapeutical effect in migraine is not clearly understood. Hypothetical mechanisms of action are discussed by the Authors in regard to the different pathogenetical events relevant to migraine. It is proposed that different pathological events can be modified by one drug and, conversely, one mechanism of action may be common to different drugs. PMID- 2251960 TI - Serum lipids in later life. PMID- 2251961 TI - Historical risk factors for stroke: a case control study. AB - The aim of this study was to determine the risk factors for admission to hospital with stroke by means of a case-control study recruiting age- and sex-matched controls from the local community. Four hundred pairs of patients and controls were recruited. Of historical factors, preceding cerebrovascular disease contributed the greatest odds of stroke (odds ratio 9.8). Taking prescribed medicines (odds ratio 2.6), regular snoring (odds ratio 3.2), smoking (odds ratio 1.7) and some factors in the family history were also significant risk factors. PMID- 2251962 TI - Is orthostatic hypotension in the elderly due to autonomic failure? AB - In order to investigate whether orthostatic hypotension in elderly people is due to autonomic nervous system dysfunction or blood vessel abnormalities, we have measured platelet and lymphocyte adrenoceptor numbers and agonist binding in addition to venous plasma catecholamine concentrations. Eight elderly subjects with orthostatic hypotension and six control elderly subjects were studied. None of the subjects had other symptoms of autonomic failure. There was no significant difference between the heart rate or plasma catecholamine responses to standing of the two groups. The orthostatic hypotension subjects had a significant rise of their plasma vasopressin levels whereas the control group had no significant change. The number of alpha 2-adrenoceptor sites in platelets was lower in the orthostatic hypotensive group compared to the controls and the binding affinity was greater than in the controls. There were no significant differences in beta adrenoceptor binding sites or affinities in isolated lymphocytes between the two groups. The similar changes in heart rate and catecholamines together with the vasopressin changes suggest that, in these elderly patients with an abnormal drop of blood pressure on standing, there is no dysfunction of autonomic pathways concerned with cardiovascular function. The lower numbers of alpha 2-adrenoceptor sites on isolated platelets in subjects with orthostatic hypotension could indicate reduced alpha 2-adrenoceptor numbers on their blood vessels which could contribute to their inability to maintain blood pressure while standing. PMID- 2251963 TI - Coronary heart disease at 70, 75 and 79 years of age: a longitudinal study with special reference to sex differences and mortality. AB - In a population study of 70-year-old people in Goteborg, Sweden, a representative sample of 449 men and 524 women was followed for nine years. The prevalence of coronary heart disease (CHD) at age 70 was about 30% in both sexes and did not change up to age 79. Myocardial infarction appeared twice as often in men as in women at age 70 but angina pectoris and ST-T changes on ECG showed no sex difference. Myocardial infarction and probable ischaemia on ECG increased significantly between ages 70 and 79 in both sexes. Half of the men with angina pectoris had a history of myocardial infarction and/or probable ischaemia on ECG criteria compared with 23% of the women. The mortality rate was twice as high in men as in women irrespective of CHD. When CHD was present at age 70 the nine-year mortality was doubled. CHD was shown to be a strong independent risk factor for death also in this age group. PMID- 2251964 TI - Rectal motility studies in faecally incontinent geriatric patients. AB - Rectal motility was assessed in three groups of geriatric patients (faecally incontinent, continent faecally impacted and control patients) to determine whether 'uninhibited' rectal contractions are a cause of faecal incontinence. The incidence of rectal contractions in response to rectal distension did not differ between the three study groups. Two-thirds of the incontinent patients were unable to retain a condom distended with water (soft-stool model) during a proctometrogram. Involuntary expulsion of this device was correlated with the presence of rectal contractions and low anal resting pressure. Involuntary expulsion of an airfilled balloon (firm-stool model) from the rectum occurred less frequently and was correlated with low resting pressure but not with rectal contractions. The contribution of 'uninhibited' rectal contractions to faecal incontinence is insignificant except for a minor role in the expulsion of liquid stool. PMID- 2251965 TI - The impact of private residential and nursing care on statutory residential and hospital care of elderly people in south Belfast. AB - Dependency levels were compared in residents of private, voluntary and statutory residential homes, private nursing homes and patients in geriatric continuing care wards in South Belfast. Dependency levels were least in private and voluntary residential homes, were similar in residential and private nursing homes, but were very much greater in the geriatric wards. Evidence of dementia was found in 23% of residents of voluntary homes, 35% of residents of private residential homes, 61% of residents of statutory residential homes, 54% of those in private nursing homes and 80% of patients in geriatric wards. Severe degrees of immobility and incontinence were commoner in nursing than in residential homes, but much commoner in geriatric wards. The number of private residential and nursing home places in the area studied has increased three- to five-fold since a previous survey in 1985. In this time, dependency levels, and frequencies of dementia, immobility and incontinence have increased in both statutory residential homes and geriatric continuing-care wards. It appears, therefore, that private residential and nursing homes take rather less dependent old people and that highly dependent old people are being concentrated in hospital. PMID- 2251966 TI - Thiamine status of healthy and institutionalized elderly subjects: analysis of dietary intake and biochemical indices. AB - Thiamine status was assessed in healthy young and elderly subjects and institutionalized elderly patients by measuring dietary intake, erythrocyte levels of thiamine and the activity of the thiamine-dependent enzyme, erythrocyte transketolase, with and without the addition of excess thiamine pyrophosphate (the TPP effect). Healthy elderly subjects had a reduced intake of thiamine compared with the younger subjects but erythrocyte levels of thiamine and the TPP effect were comparable, suggesting adequate thiamine status. The institutionalized elderly patients had a low intake of thiamine compared with the healthy elderly as well as abnormal biochemical indices suggestive of suboptimal thiamine status. Thiamine deficiency does not appear to be a problem in healthy elderly people but those in institutions are at risk of deficiency which might adversely affect their clinical state. PMID- 2251967 TI - Association of muscle strength with functional status of elderly people. AB - We have studied the association of muscle strength (quadriceps, biceps, handgrip), measured by a portable chair technique, with functional status (Barthel Index, manual dexterity, Mental Test Score, history of falls, fracture, prescribed drugs), in a sample of 92 elderly subjects attending a Local Authority Day Centre and Day Hospital. Anthropometric measurements and hand-grip strength were also measured in 30 young controls. Muscle area, mass and strength were significantly greater in young controls. Elderly men had significantly greater muscle area, mass and strength than elderly women. Muscle strength correlated with several measures of functional status. Using stepwise multiple regression, an independent association of muscle strength with manual dexterity, Barthel Index and receipt of domiciliary services is demonstrated. PMID- 2251968 TI - Post-operative urinary retention in women: management by intermittent catheterization. AB - We have investigated the value of intermittent catheterization in the management of post-operative urinary retention occurring in elderly women after operative fixation of lower limb fracture. Eleven patients, aged 70-86, underwent intermittent catheterization two or three times daily for between 9 and 40 days as inpatients, and one patient continued intermittent self-catheterization at home for 3 months after discharge. Ten patients became continent. One severely disabled lady required an indwelling catheter. Intermittent catheterization is safe and practical, with several advantages over indwelling catheterization in the management of post-operative urinary retention during inpatient rehabilitation. PMID- 2251969 TI - Cause of death in Alzheimer's disease. AB - Bronchopneumonia was the commonest cause of death in 84 elderly patients suffering from Alzheimer's disease. The cause of death as stated on the death certificate agreed with the pathological diagnosis in 77% of cases. In 30%, no mention of the presence of a dementia syndrome was recorded on the death certificate. An increased willingness to record the presence of a dementia syndrome and a higher autopsy rate would increase the accuracy of death certification in Alzheimer's disease. PMID- 2251970 TI - Fallers and non-fallers. PMID- 2251971 TI - Plasma osmolality and survival of elderly continuing-care patients. PMID- 2251972 TI - Analysis of immune response in oral tumors. AB - Currently, there is widespread disagreement over the role of the immune system in controlling, via the major histocompatibility complex, the organism's response to cells in the process of tumoral degeneration. One possible mechanism by which tumoral cells escape detection by the antitumoral surveillance system is the lack of expression of HLA class I molecules. The APAAP technique was used to study the levels of expression of these molecules and other cell markers on 27 oral cavity tumors. Heterogenous class I expression was recorded, some tumors completely lacking class I antigens. Similar patterns of expression were found for beta-2 microglobulin and ABC molecules (different class I chains encoded in different chromosomes). The number of DR/DP positive cells was similar to the number of immune cells infiltrating the tumors. Statistical analyses failed to show any significant relationship between class I antigen expression and the anatomoclinical parameters of tumoral aggressivity considered. PMID- 2251973 TI - Changes in the lymphocyte response and in the production of IgE regulatory factors in relation to the course of immunotherapy. AB - In previous studies we described isotype-specific but antigen non-restricted soluble factors produced by human lymphocytes. In subsequent studies we demonstrated changes in the production of these factors during the course of immunotherapy (IT) by testing them on lymphocytes from normal healthy controls and allergic patients. Through these studies we confirmed that there exists a difference in lymphocytes' responsiveness to soluble factors between both groups. In this report, we investigated the effect of soluble factors on lymphocytes from allergic patients without IT (LyG1) and with IT longer than 2 years (LyG4). Peripheral blood samples were collected from healthy controls and allergic patients at different time periods of IT, and bidirectional mixed cultures were performed with the isolated lymphocytes. Supernatants obtained from chromatography were tested on lymphocytes of allergic patients without IT and with IT greater than 2 years to determine their effect on IgE synthesis. Long periods of IT reduce the production of Suppressor Factors (SF) by allergic patients as well as their responsiveness. Long periods of IT increase the responsiveness of lymphocytes of allergic patients to Enhancing Factors (EF) and decrease EF production. We propose a "receptor hypothesis" to explain these events. PMID- 2251974 TI - Study of various immunological parameters in the diagnosis of allergy to penicillin G and its derivatives. AB - The objective of this paper was to draw up an efficient and safe study protocol to diagnose allergy to beta-lactam antibiotics. Seven hundred and fifty patients with clinical histories suggesting penicillin allergy were studied. RAST to penicilloyl G/V, skin tests with PPL, MDM, penicillin G and ampicillin, epicutaneous tests with differed type reactions and a provocation test (in case of the negative results of the other tests) were performed on the patients. The incidence of this pathology is very low (6.5%) and atopic patients do not present greater predisposition to suffer from it than the general population. By carrying out RAST and skin tests with PPL, MDM, penicillin G and ampicillin we arrived at the diagnosis, in the anaphylactic type charts, in 97.5% of the cases. In reactions of a differed type, by performing patch tests we arrived at the diagnosis in 50% of the cases. PMID- 2251975 TI - Secretory IgA deficiency in pediatric patients: clinical and laboratory follow up. AB - This is a prospective three-year (1985-1988) clinical and laboratory follow-up study of 43 pediatric patients without any measurable secretory IgA, intending to describe the their natural course. We also intended to detect evidence which may allow to predict their future outcome, whether they would become asymptomatic or end up developing chronic disease. A direct statistical correlation was found between those patients who normalize their secretory IgA levels and their course in an asymptomatic state. Thus, if a child does not have any sIgA at all, the relative risk to get sick is 0.86 (86%), while in those having sIgA within normal ranges, the relative risk of disease decreases to 0.46 (46%), representing a p value less than or equal to 0.05. Among the analyzed variables and their influence on the fact that a patient may or may not synthesize sIgA, none of them showed a predictive value for bronchial asthma by itself. However, when sIgA and total serum IgE levels, were analyzed together (being the two variables demonstrating to influence), the probability of becoming asthmatic is much greater in the ones with elevated total serum IgE and absent sIgA. This group is significantly different from the one with normal IgE and sIgA levels (p less than or equal to 0.001). According to our experience in evaluating and controlling a pediatric patient with repeated episodes of bronchial obstruction and lacking sIgA, an immediate strict environmental control should be established in order to avoid all possible contacts with allergens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251976 TI - Clinical, biochemical and immunological effectiveness of diacetyl-splenopentin (BCH 069) in hay fever. AB - Diacetyl-splenopentin (BCH 069) is a new pentapeptide of splenin modified by twofold acetylation. BCH 069 has thymopentin-like activity demonstrated by in vivo animal and in vitro human studies. Two groups of patients received 50 mg BCH 069 and placebo, respectively, by subcutaneous injection 3 times weekly for 4 weeks. The third group of patients received 50 mg BCH 069 by intravenous injection 3 times weekly for 6 weeks. The therapy was carried out during the peak of the pollen season. BCH 069 intravenous treatment was found to be significantly superior to placebo treatment in reducing clinical symptoms. Biochemical inflammatory signs were not observed. No increase of bronchomotoric reactivity was established in comparison to the placebo group. There was a significantly lower increase in gras-spollen specific IgE and IgG4 in the intravenous group of BCH 069. Subcutaneous therapy with BCH 069 was not effective. The study demonstrated that BCH 069 used intravenously induces clinical improvement in patients suffering from hay fever. Thus the possibility to influence hyperreactive conditions of the immune system has been confirmed. The study indicates that various application routes of BCH 069 have different effects on the immune system. PMID- 2251977 TI - Occurrence and clinical profile of the sensitization to Chenopodium in the province of Cordoba (Spain). AB - The sensitization to pollen from the Amarantaceae and Chenopodiaceae families is responsible for some pollinoses according to various authors. Following an aeropalynological carried out by the Botany Division of our University, we investigated the sensitization to Chenopodium in our pollinic patients in order to establish their clinical patterns. We evaluated 14 variables in Chenopodium sensitive (CHE +) and nonsensitive (CHE -) patients; the results were analysed by using a computerized statistical programme. Of the 1,000 records reviewed, 38% corresponded to pollinic patients, of whom 8.42% were sensitive to pollen from this family. We found no significant differences between the two groups in the parameters representative of atopic features (e.g. eosinophilia, IgE). However, marked differences were indeed found in the age of appearance of symptoms, frequency of clinical pictures, origin of the patients, duration of the symptoms and evolution upon immunotherapeutic treatment not involving this antigen. These findings endow the sensitization to Chenopodium with special features which should be taken into account in choosing a specific treatment. PMID- 2251978 TI - Seasonal and daily variation of Aspergillus Mich. Ex Fr. spores in the atmosphere of Cordoba (Spain). AB - The atmosphere contains a complex of spores whose concentration and variation have been the subject of much study, mainly because of the relevance of fungi to allergic and aerobiological pollution problems. This paper reports on the cataloguing of the Aspergillus species present in the atmosphere of Cordoba, their seasonal and daily variation and their potential relationship with meterological parameters. The sampling was carried out in the city of Cordoba by using a volumetric trap on a culture medium; three samplings were done daily at various times throughout the year (May 1986-April 1987). An unreplicated variance analysis was applied to two variation sources in order to check for statistically significant differences between the number of colony forming units (CFU) detected at each sampling time. Meterological data and concentrations were also contrasted through statistical correlation tests. A total of 94,200 colonies were counted; 32.3% of all were from 24 species of the Aspergillus genus, of which A. fumigatus Fresen, was found to be the most abundant. Aspergillus niger Van Tiegh, A. oryzae (Ahlburg) Cohn, A. terreus Thom and A. ochraceus Wilhelm also occurred at a high frequency. All these species were detected throughout the year and in virtually all of the samplings, but particularly in autumn, which was the most favourable period for the occurrence of their spores, which in turn seemed to be conditioned by the time at which samplings were carried out, at least for the six most frequent species--A. candidus expected as it only occurred occasionally. Finally, the occurrence of spores of this genus seems to be positively and negatively correlated with meterological factors such as the wind speed and the temperature, respectively. PMID- 2251979 TI - Alveolar macrophage: origin, kinetics and relationship with cells of the alveolo interstitial region. AB - The alveolar macrophage (AM) is the most abundant immunocompetent cell in the alveolus. Studies of this cell type have usually focused on its morphological, enzymatic or functional aspects but little attention has been paid to its origin or kinetics or to the functional relationship it has with local structures. There were two aims in this present work: firstly, to review the current data relating to the origin of this cell type, emphasizing the following aspects: Immediate and remote precursors of the alveolar macrophage. The proliferative capacity of the alveolar macrophage. Its routes of elimination. Regulating factors. Secondly, the main relationships of the alveolar macrophage with other cells of the alveolus and pulmonary interstitium were considered. This was done from two different viewpoints: The action of the alveolar macrophage on adjacent cells. The actions of local cells of the alveolar macrophage itself. PMID- 2251980 TI - 1990 Yant memorial award lecture. Science, occupational exposure limits, and regulations: a case study on organochlorine solvents. PMID- 2251981 TI - Positional stability of five insert-type hearing protectors as a function of controlled jaw movement. AB - Five insert-type hearing protectors (three viscose foam, one multiflanged, and one glass fiber) were evaluated for lateral drift in the ear canal as a result of 30 min of controlled jaw movement. The lateral drift was compared to changes in attenuation for the same protectors over the same duration of jaw movement. The ranked correlation of positional and attenuation stability was very low (Spearman Rho = 0.3). Possible explanations for this observation are discussed. PMID- 2251982 TI - Assessment of potential biases in the application of MSHA respirable coal mine dust data to an epidemiologic study. AB - Systematic errors in exposure data will result in biased estimates of the exposure-response relationship derived from epidemiologic analyses. Thus, adjustment of exposure data to account for identified errors may provide for a more accurate assessment of effect. In preparing to apply respirable coal mine dust exposure data collected by the Mine Safety and Health Administration (MSHA) to a study of the pulmonary status of underground coal miners, an assessment of potential systematic errors was undertaken. Potential errors stemming from adjustment of controls during sampling, concentration-dependent sampling, truncation of sampling results, identified sampling equipment problems, and a disproportionate number of low concentration samples in mine operator-collected samples were identified and evaluated. Methods to account for these errors and adjust mean exposures by mine, occupation, and year are given. PMID- 2251983 TI - Thermal discomfort of respiratory protective devices. AB - Respiratory protective devices which would protect the wearer against noxious material and gases are not worn in many of the appropriate circumstances. They have been said to feel uncomfortable and hot. In the present study, six men and six women in a 25 degrees C room reported on facial discomfort, thermal sensation, and sweating while wearing three different types of half-facepiece respirators requiring tidal airflow. Skin temperature of the face was measured using a thermocouple taped to the nasolabial fold. The subjects reported that the face felt comfortable when the skin temperature was 34 degrees C or below. However, at skin temperatures above 34.5 degrees C, the face felt increasingly warm, uncomfortable, and sweaty. This finding is similar to that reported previously when subjects wore a half-facepiece respirator supplied continuously with warm, humid air. The conclusion is that thermal conditions of the face contributed to, and may possibly dominate, the discomfort of wearing respiratory protective devices. PMID- 2251984 TI - Perchloroethylene exposure assessment among dry cleaning workers. AB - Perchloroethylene (Perc), the most widely used solvent in dry cleaning, is toxic to the liver, kidneys, and central nervous system and may be a human carcinogen. In the Detroit area, as part of a project investigating the health status of dry cleaning workers, an exposure assessment was carried out in dry cleaning plants using perchloroethylene. Breath samples were obtained from each participant, and time-weighted average (TWA) breathing zone air samples were obtained using passive dosimeters on a subset expected to experience a range of exposures. Perc in breath and Perc in air were highly correlated (r2 = 0.75, p less than 0.0001). On average, operators of dry cleaning equipment experienced significantly more exposure than nonoperators. Also, employees working in shops that use transfer equipment (requiring physical transfer of Perc-saturated clothing from washers to dryers) showed significantly higher exposure than those in shops utilizing dry-to dry machinery (permitting washing and drying in one machine in a single cycle). One or more air samples in every transfer shop exceeded the recently revised Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 25 ppm, while no air samples in dry-to-dry shops exceeded this limit. The results suggest concern for exposures to operators in transfer shops and that compliance with the PEL is achievable by engineering controls with presently existing technology. PMID- 2251985 TI - Changes in myocardial ischemic threshold during daily activities. AB - This study assesses the variations in myocardial ischemic threshold (heart rate at the onset of ischemia) during daily activities in patients with ischemic episodes on Holter monitoring. Eighty patients with known coronary artery disease, positive treadmill stress test results and greater than or equal to 2 ischemic episodes during a 24-hour period of Holter monitoring were studied. The lowest and the highest ischemic thresholds were determined for each patient. The mean lowest ischemic threshold was 85 beats/min, and the mean highest ischemic threshold was 109 beats/min. The highest ischemic threshold was identical to ischemic threshold values noted during exercise. Of the 895 ischemic episodes, 654 (74%) were preceded by a moderate (greater than 10%) increase in heart rate. The variability of ischemic threshold (difference in percentage between the highest and lowest ischemic thresholds) increased with the number of ischemic episodes (range 2 to 60%). However, in different patients with a similar number of ischemic episodes, different variability was observed. These differences in ischemic thresholds are probably indirect indicators of the vasomotor activity of the coronary arteries in different patients. PMID- 2251986 TI - Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. AB - A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or beta blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p less than 10(-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration greater than 150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects. PMID- 2251987 TI - Prehospital thrombolysis in acute myocardial infarction. AB - The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs 2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function. PMID- 2251988 TI - Acute myocardial infarction and chest pain syndromes after cocaine use. AB - Seventy patients hospitalized with chest pain after cocaine use were retrospectively evaluated to define the risk and clinical course of acute myocardial infarction (AMI). AMI developed in 22 patients (31%) and transient myocardial ischemia was seen in an additional 9 patients (13%). Coronary risk factors did not distinguish those who developed AMI from those who did not. The presenting electrocardiogram was abnormal in 20 of 22 patients who evolved AMI and in 19 of 48 of those who did not. Creatine kinase levels were elevated in 75% of the patients, including 65% of those who did not develop AMI, but creatine kinase-MB elevations were only observed in the AMI group. The route of cocaine administration did not predict AMI and there was no predilection for a particular coronary vascular bed. The length of time between drug use and onset of AMI pain was often quite prolonged (median interval, 18 vs 1 hour in the non-AMI group). Eight of the patients with AMI underwent cardiac catheterization and 4 had significant coronary narrowing. PMID- 2251989 TI - Recanalization of chronic total coronary arterial occlusions by percutaneous excimer-laser and laser-assisted angioplasty. AB - A low primary success and high restenosis rate after recanalization of chronic total occlusions by conventional coronary angioplasty have encouraged the application of new interventional techniques like excimer-laser angioplasty. In 39 patients with a coronary occlusion for 1 to 12 months, recanalization was attempted by laser angioplasty through a multifiber-catheter coupled to a pulsed XeCl excimer laser. After successful passage of the occlusion by a standard guidewire in 27 patients (69%), the laser catheter was advanced over the central guidewire and crossed the occlusion in 25 patients (64%). In 2 patients with unsuccessful passage of the laser catheter, the subsequent attempt with a low profile balloon catheter also failed. In 19 of the 25 patients with successful laser recanalization, the residual stenosis exceeded 50% and was therefore followed by additional balloon angioplasty. The average residual stenosis after laser was 61 +/- 17% of the vessel diameter, and after balloon angioplasty 28 +/- 9% (n = 19), whereas after laser angioplasty alone it was 38 +/- 5% (n = 6). No complications associated with the laser application were observed. Angiographic control after 24 hours showed a reocclusion of 2 (8%) recanalized vessels. In this pilot study, laser angioplasty proved to be a safe and feasible method for the treatment of chronic total coronary occlusions. Because it was necessary to guide the catheter by a central wire, the primary success was limited by a successful passage of the wire of the occlusion. The rate of stand-alone laser angioplasty has to be increased by future improvements of the technique to enable a comparative evaluation of this method with conventional angioplasty. PMID- 2251990 TI - Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting. AB - Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/ 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death. PMID- 2251991 TI - Temporal relation between left ventricular dysfunction and chest pain in coronary artery disease during activities of daily living. AB - Forty-three ambulatory patients with angina of increasing frequency underwent continuous monitoring of left ventricular (LV) function for an average of 2.9 +/- 1.9 hours to determine the incidence and temporal sequence of LV dysfunction, ST segment depression and chest pain. Indicators of ischemia were: a decrease in ejection fraction greater than 5% lasting greater than 1 minute; horizontal or downsloping ST-segment depression of greater than or equal to 1 mm; or onset of the patient's typical chest pain complex, or a combination of these. During the monitoring interval, subjects performed daily activities such as sitting, walking, climbing stairs and eating. In 11 patients, 22 episodes of chest pain or ST-segment depression, or both, were observed. Eighteen episodes were accompanied by a decrease in ejection fraction (9 patients); chest pain accompanied the decrease in ejection fraction during 13 episodes, whereas ST-segment changes occurred during 7. In 12 of 13 episodes the decrease in ejection fraction began earlier than the onset of chest pain, whereas in 1 patient ejection fraction decrease and chest pain onset started at the same time. The average interval from a decrease in ejection fraction to the onset of chest pain was 56 +/- 41 seconds (range 0 to 120). ST changes occurred after the onset of a decrease in ejection fraction in 6 of 7 episodes. The average interval from the onset of ejection fraction decrease and the onset of ST change was 99 +/- 91 seconds. These data suggest that LV dysfunction manifested by a decrease in ejection fraction is an earlier indicator of myocardial ischemia than is angina pectoris or electrocardiographic evidence of ischemia. PMID- 2251992 TI - Recanalization of chronic, totally occluded coronary arteries by new angioplasty systems. AB - The benefit and safety of new angioplasty equipment as compared with the conventional guidewire approach was evaluated in 154 consecutive patients. with chronic, totally occluded coronary arteries. The protocol followed a stepwise design: first, conventional guidewires and low-profile balloons were used, followed by "balloon-on-the-wire" systems (Probe, Ace) or by a shaft-enforced, tip-deflecting catheter (Omniflex). In 97 patients with occlusions of 2 to 12 weeks' duration, recanalization was achieved in 51 patients (53%) with the conventional approach and in 29 patients with the new devices (balloon-on-the wire [n = 5], Omniflex [n = 24]), thereby raising the success rate to 82%. In 57 occlusions of greater than 12 weeks' duration, the recanalization attempt was successful in 58%, mediated in 16 patients (28%) by the Omniflex catheter and in 5 patients by balloon-on-the-wire systems. There were no life-threatening complications and only 1 (0.6%) emergency bypass operation was necessary. New angioplasty devices are therefore of considerable value in the attempt to improve the results of coronary angioplasty in chronic total occlusions. PMID- 2251993 TI - Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion. AB - The prevention of graft occlusion by aspirin (100 mg/day) or heparin followed by phenprocoumon was investigated in a randomized trial in 235 patients after aortocoronary bypass operation. Aspirin treatment started 24 hours before, and heparin 6 hours and phenprocoumon 2 days after surgery. The results of the vein graft angiography and the clinical outcome 3 months postoperatively did not differ: 22% of 218 vein graft distal anastomoses in the aspirin group and 20% of 272 in the anticoagulant group were occluded. At least 1 occluded distal anastomosis was present in 38% of 74 patients in the aspirin-treated group and in 39% of 86 in the anticoagulant group. Worst-case analysis of all randomized patients showed graft occlusions, cardiovascular complications or lost to follow up in 42% of 122 aspirin-treated patients compared with 41% of 113 patients treated with anticoagulants. For grafts with endarterectomy the occlusion rate was lower in the aspirin (12% of 49) than in the anticoagulant (22% of 41) group (p less than or equal to 0.05). Increased perioperative blood loss in the aspirin group (1,211 +/- 814 ml in the first 48 hours vs 874 +/- 818 ml in the anticoagulant group [p less than or equal to 0.001]) without a higher reoperation rate indicates effective platelet inhibition with low-dose aspirin. Because occlusion rates were equal but high in these patients with advanced stage of coronary artery disease, a combination of low-dose aspirin and anticoagulation should be investigated to reduce graft occlusion rates further. PMID- 2251994 TI - Left ventricular filling impairment in asymptomatic chronic alcoholics. AB - Systolic left ventricular dysfunction is relatively common in even asymptomatic alcoholics, but whether diastolic function is also altered is much less well studied. We used M-mode and Doppler echocardiography to study left ventricular size, mass, systolic function and diastolic filling in 32 alcoholics free of clinically detectable heart disease and in 15 healthy control subjects. Left ventricular mass index and posterior wall thickness were higher in alcoholics than in controls, but there was no statistically significant difference either in end-diastolic size or in systolic ventricular function. More abnormalities were found in the Doppler indexes of diastolic function, however. The alcoholics had a prolonged relaxation time (200 +/- 6 vs 184 +/- 5 ms [mean +/- standard error], p less than 0.05), a decreased peak early diastolic velocity (52 +/- 2 vs 60 +/- 3 cm/s, p less than 0.05), a slower acceleration of the early flow (410 +/- 18 vs 552 +/- 43 cm/s2, p less than 0.01), and a higher atrial-to-early peak velocity ratio (0.74 +/- 0.04 vs 0.60 +/- 0.05, p less than 0.05). This pattern of changes suggests a primary abnormality in the relaxation of the left ventricle. In multivariate analyses, the abnormalities in the Doppler indexes were independent of the duration of alcoholism, the quantity of the most recent ethanol exposure and the increased mass of the left ventricle. Impaired early filling of the left ventricle due to delayed relaxation is common in asymptomatic alcoholics and may in fact be the earliest functional sign of preclinical alcoholic cardiomyopathy. PMID- 2251995 TI - Physiologic peripheral pulmonic stenosis in infancy. AB - We studied 14 premature infants with the clinical diagnosis of peripheral pulmonic stenosis (PPS) and 15 normal full-term neonates by echocardiographic Doppler examinations. The PPS group had an average main pulmonary artery (PA) diameter similar to the control group (0.91 vs 0.96 cm, difference not significant), but had smaller branch PA diameters: right PA = 0.41 vs 0.50 cm, p less than 0.001, and left PA = 0.41 vs 0.49 cm, p less than 0.001. The PPS group also had greater peak velocities in the main PA (76 vs 63 cm/s, p less than 0.05), right PA (193 vs 118 cm/s, p less than 0.001) and left PA (187 vs 123 cm/s, p less than 0.001). Similarly, the ratio of peak velocity in the branch/main PA was greater for the PPS group: right/main PA peak velocity = 2.91 vs 1.92, p less than 0.01, and left/main PA peak velocity = 2.73 vs 1.99, p less than 0.05. The calculated right ventricular output for the PPS group was more than the control group: 437 vs 261 ml/min/kg, p less than 0.001. Hematocrits were not done on the control group, but the PPS group had an average hematocrit which was low (34%). It is concluded that patients with PPS have mild underdevelopment of the PA branches, with consequent increased flow velocity and turbulent flow. This turbulent flow may be contributed to by increased cardiac output and mild anemia. PMID- 2251996 TI - Coronary arteries in truncus arteriosus. AB - The origin and distribution of the coronary arteries was described in 39 autopsy specimens of truncus arteriosus (TA). The specimens were classified according to the number and the patterns of the truncal cusps. The position of the truncal cusps was defined in relation to intracardiac structures, namely, the atrioventricular orifices. Bicuspid truncal valves were observed in 8 cases (21%), tricuspid in 22 cases (56%) and quadricuspid in 9 cases (23%). All tricuspid valves had 2 anterior and 1 posterior cusp. Great variability in the origin of the coronary arteries was observed, with a tendency for the right coronary artery to arise from the anterior right quadrant and for the left coronary artery to arise from the anterior and left quadrant. Such a tendency was observed in 50% of the bicuspid, in 59% of the tricuspid and in 66% of the quadricuspid valves. The anatomic right ventricle was always observed to be vascularized by a right coronary artery, and the anatomic left ventricle by a left coronary artery, even in cases in which there was a single coronary trunk. The anterior surface of the right ventricle was crossed by a right coronary artery in 5 cases. A single coronary artery was observed in 7 cases (18%). Embryologic considerations are offered, especially regarding the relation between the observed variability in coronary artery patterns in TA and the absence of the truncal septation. PMID- 2251997 TI - Spectrum of hemodynamic changes in cardiac tamponade. AB - To investigate the pathophysiology of cardiac tamponade, the hemodynamics of 77 consecutive patients with greater than 150 ml of pericardial effusion were studied. Patients were classified into 3 groups based on the equilibration of intrapericardial with right atrial and pulmonary arterial wedge pressures (mm Hg): group I (n = 16), intrapericardial pressure was less than right atrial and pulmonary arterial wedge pressures; group II (n = 13), intrapericardial pressure was equilibrated with right atrial but not pulmonary arterial wedge pressures; group III (n = 48), intrapericardial pressure was equilibrated with right atrial and pulmonary arterial wedge pressures. Pericardiocentesis produced the following changes: group I--significant (p less than 0.03) decreases in intrapericardial pressure (7 +/- 2 mm Hg), right atrial pressure (3 +/- 2 mm Hg), pulmonary arterial wedge pressure (2 +/- 2 mm Hg), and the inspiratory decrease in arterial systolic pressure (3 +/- 4 mm Hg) but no significant change in cardiac output; group II--significant (p less than 0.02) decreases in intrapericardial pressure (11 +/- 5 mm Hg), right atrial pressure (6 +/- 4 mm Hg), pulmonary arterial wedge pressure (4 +/- 5 mm Hg), and inspiratory decrease in arterial systolic pressure (8 +/- 7 mm Hg), and increase in cardiac output (1.1 +/- 1.2 liters/min); group III--significant (p less than 0.001) decreases in intrapericardial pressure (16 +/- 7 mm Hg), right atrial pressure (9 +/- 4 mm Hg), pulmonary arterial wedge pressure (8 +/- 5 mm Hg), inspiratory decrease in arterial systolic pressure (17 +/- 11 mm Hg), and increase in cardiac output (2.8 +/- 1.5 liters/min). The changes after pericardiocentesis in all parameters were significantly (p less than 0.05) greater in group III than in groups I or II except for the change in right atrial pressure, which was not significantly different in groups II versus III. The changes after pericardiocentesis indicate pericardial effusion caused the greatest abnormalities in group III but also caused significant abnormalities of pressure and flow in group II and of pressure alone in group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2251998 TI - Transesophageal echocardiography in critically ill patients. AB - The feasibility, safety and clinical impact of transesophageal echocardiography were evaluated in 51 critically ill intensive care unit patients (28 men and 23 women; mean age 63 years) in whom transthoracic echocardiography was inadequate. At the time of transesophageal echocardiography, 30 patients (59%) were being mechanically ventilated. Transesophageal echocardiography was performed without significant complications in 49 patients (96%), and 2 patients with heart failure had worsening of hemodynamic and respiratory difficulties after insertion of the transesophageal probe. The most frequent indication, in 25 patients (49%), was unexplained hemodynamic instability. Other indications included evaluation of mitral regurgitation severity, prosthetic valvular dysfunction, endocarditis, aortic dissection and potential donor heart. In 30 patients (59%), transesophageal echocardiography identified cardiovascular problems that could not be clearly diagnosed by transthoracic echocardiography. In the remaining patients, transesophageal echocardiography permitted confident exclusion of suspected abnormalities because of its superior imaging qualities. Cardiac surgery was prompted by transesophageal echocardiographic findings in 12 patients (24%) and these findings were confirmed at operation in all. Therefore, transesophageal echocardiography can be safely performed and has a definite role in the diagnosis and expeditious management of critically ill cardiovascular patients. PMID- 2251999 TI - The developmental phase of modern coronary artery surgery. PMID- 2252000 TI - Atrial isomerism in the heterotaxy syndromes with asplenia, or polysplenia, or normally formed spleen: an erroneous concept. PMID- 2252001 TI - Statistical significance of Veterans Administration Vasodilator Heart Failure Trial results. PMID- 2252002 TI - Transient electrocardiographic changes of elective coronary angioplasty compared with evolutionary changes of subsequent acute myocardial infarction observed with continuous three-lead monitoring. PMID- 2252003 TI - Long-term clinical and angiographic follow-up of percutaneous transluminal coronary angioplasty in patients greater than or equal to 65 years of age. PMID- 2252004 TI - Insurance reimbursement for preventive cardiology services. PMID- 2252005 TI - Prognostic value of junctional recovery times and long-time follow-up of complete atrioventricular nodal block at a young age. PMID- 2252006 TI - Seasonal variation in occurrence of acute atrial fibrillation and relation to air temperature and sale of alcohol. PMID- 2252007 TI - Risk factors for atrial fibrillation after coronary artery bypass grafting. PMID- 2252008 TI - Efficient estimation of the heart period power spectrum suitable for physiologic or pharmacologic studies. PMID- 2252009 TI - Transvenous atrial septal defect occlusion by the buttoned device. PMID- 2252010 TI - Experience with a newly developed pericardiocentesis set. PMID- 2252011 TI - Relation of mean pulmonary arterial wedge pressure and left ventricular end diastolic pressure. PMID- 2252012 TI - Ventricular arrhythmias after balloon aortic valvuloplasty. PMID- 2252013 TI - The who's and when's of therapy for Helicobacter pylori. PMID- 2252014 TI - Normal hepatic function foiled by HBV infection after liver transplantation. PMID- 2252015 TI - Rectal hyperplastic polyps: now you see them, now you don't--a differential point. PMID- 2252016 TI - Controversies, dilemmas, and dialogues. Nonsurgical gastrostomy: X-ray or endoscopy? PMID- 2252017 TI - Controversies, dilemmas, and dialogues. When is colonoscopic resection of an adenomatous polyp containing a "malignancy" sufficient? PMID- 2252018 TI - Aging-related alterations in human upper esophageal sphincter function. AB - Recent improvements in manometric catheters have made measurement of pharyngeal (P) and upper esophageal sphincter (UES) swallowing mechanics more reliable. Few studies have attempted to evaluate the effect of normal aging on P and UES mechanics. Pharyngeal and upper esophageal sphincter dynamics were studied in 10 healthy elderly adults (age greater than 60; range 62-79 yr) and 10 younger adults (age less than 60; range 24-59 yr). A solid-state intraluminal transducer system was used with a proximal unidirectional Konigsberg microtransducer and a circumferential (sphincter) transducer located 5 cm distally. Mean resting UES pressure was significantly (p less than 0.05) lower in the elderly than in the younger subjects (52 +/- 5 vs 72 +/- 6 (SE)) mm Hg. A significant inverse relation (R = -0.54; p less than 0.02) was found between age and resting UES pressure. Time from peak of pharyngeal contraction to UES nadir was significantly (p less than 0.05) shortened in the healthy elderly vs younger controls (10 +/- 30 vs 90 +/- 20 ms) during dry swallows. Our studies indicate that aging is associated with lower resting UES pressure and delayed UES relaxation, relative to the pharyngeal peak. PMID- 2252019 TI - Helicobacter pylori infection: a simplified diagnostic approach. AB - We evaluated the diagnostic accuracy of endoscopic finding of nodular antritis and rapid urease test (RUT) in order to simplify the approach to the diagnosis of Helicobacter pylori (H. pylori) infection. Forty-four consecutive patients (mean age 7.9 yr, range 6-13 yr) referred because of recurrent abdominal pain as the main symptom, were prospectively investigated for the presence of H. pylori. H. pylori positivity or negativity was defined as the concordance of two of the following tests: RUT, microbiologic culture, and histologic examination on bioptic samples. RUT sensitivity was 100%, whereas specificity was 87.5%. The presence of nodular antritis had a sensitivity of 96.4% and specificity of 87.5% in H. pylori infection diagnosis. The predictivity value of combined RUT and nodular antritis, whether positive or negative, was 100%. Only in case of discordance do we suggest the utilization of other expensive tools for diagnosis of H. pylori infection. PMID- 2252020 TI - Helicobacter pylori infection in patients with acquired immune deficiency syndrome. AB - A controlled study was conducted on patients with human immunodeficiency virus (HIV) infection referred for upper endoscopy to evaluate the prevalence of Helicobacter pylori (H. pylori) infection. Four different stains and culture for H. pylori were performed on biopsy specimens from the gastric antrum. Sixteen (40%) of 40 patients with acquired immune deficiency syndrome (AIDS) or AIDS related complex (ARC) were diagnosed to be infected with H. pylori versus 14 (39%) of 36 age-matched control patients. Eight of 15 AIDS/ARC patients without AIDS-related esophagogastroduodenal findings (53%) were infected with H. pylori versus 8/25 (32%) with endoscopic findings typical of AIDS. No invasion of the lamina propria by H. pylori was noted in any patient. Active chronic gastritis was present in 60% of AIDS/ARC patients and 61% of controls. Fifty-eight and 59%, respectively, of active chronic gastritis cases were infected with H. pylori. All the H. pylori infections, except one, were found in patients with chronic gastritis. In AIDS/ARC patients, H. pylori infection and active chronic gastritis are as common as in other patients referred for upper endoscopy. They may play a pathogenic role, especially when endoscopic AIDS-related findings are lacking. Cell-mediated immune deficiency does not appear to increase the risk of infection with H. pylori. PMID- 2252021 TI - Incidence and prevalence of ulcerative colitis in the upper Galilee, Northern Israel, 1967-1986. AB - An epidemiological study of ulcerative colitis was performed in the Upper Galilee, Israel, over a 20-yr period (1967-1986). The average annual incidence of ulcerative colitis was 2.23 per 100,000 population, and the prevalence on December 31, 1986, was 44.58 per 100,000. Considering the fact that strict steps were taken to include only definite cases, these figures are probably an underestimation. An increase of the average annual incidence from 0.88 in the period 1967-1976 to 3.79 in 1977-1986 was found. When the data were stratified according to ethnic groups, the highest average annual incidence and the highest point prevalence was found in Israeli-born Jews (6.9 and 138.2 per 100,000 population, respectively). When Jewish residence patterns were compared, the highest average annual incidence and point prevalence were found among Kibbutz members (5.52 and 110.39, respectively), and the lowest (1.94 and 38.76) among Moshav inhabitants. There were 10 Arab patients with an average annual incidence of 0.96 and a point prevalence of 19.27. There were 25 women and 28 men (female:male ratio of 0.89). Among the Jews, the female:male ratio was 1.04. Peak incidence was found in the 25- to 34-yr-old range. No second peak was noticed. Anemia was demonstrated in 66.6% of the women and 27.5% of the men in our study. We suggest that the increase in UC incidence and prevalence in Israeli and Asia/africa-born Jew and in Arabs in the Upper Galilee points toward environmental factors in the etiology of this disease. PMID- 2252022 TI - Failure of hepatitis B immunization in liver transplant recipients: results of a prospective trial. AB - Twenty patients with advanced liver disease, in need of transplantation, were given three injections of 20 micrograms and three injections of 40 micrograms hepatitis B vaccine to see if an antibody response could be obtained. Only 20% of patients developed measurable anti-HBs. One who failed to develop anti-HBs developed chronic hepatitis B after exposure to her infected sexual partner. Type of liver disease in the native liver, age, sex, sexual preference, timing of immunization (before or after transplantation), and dosage of hepatitis B vaccine did not seem to explain the lack of immunologic response to hepatitis B vaccine. It is presumed that immunosuppression, both from the underlying disease and from immunosuppressive medications, best explains our findings. Liver transplantation patients infrequently benefit from hepatitis B vaccine. It is possible that other vaccines given to prevent viral and bacterial illness may also fail to elicit immunologic response in such patients. PMID- 2252023 TI - Increasing prevalence of gallstones in male veterans with alcoholic cirrhosis. AB - Cases of alcoholic cirrhosis identified at necropsy were studied for the prevalence and type of gallstones, compared with age- and race-matched autopsy controls. Data were examined from 1970-1977 and 1980-1987. In the early sample of 460 cirrhotic patients, 33% had gallstone disease, contrasted with 12% in the controls. In the 1980s, among 299 patients, 46% had gallstone disease, whereas it was present in 13% of the controls. The prevalence of stones was significantly greater in the patients than in the controls for both time periods and, among the patients, was significantly greater in the 1980s than in the 1970s (p less than 0.05). A comparison of cirrhotic patients with and without gallstones indicated a significantly higher incidence of ascites in the patients with gallstones. The gallstones in cirrhotics were more frequently pigmented than in the controls in both time periods. In 100 living patients with advanced cirrhosis studied by sonography during 1987 and 1989, the prevalence of gallstones was 43%, almost the same as the autopsy sample from 1980-1987. In these cirrhotics, ascites, encephalopathy, and varices were more prevalent in the patients with stones than those without. We conclude that pigmented gallstones are increasing in cirrhosis of the liver related to the severity of the liver disease. PMID- 2252024 TI - Plasma fatty acid profile in advanced cirrhosis: unsaturation deficit of lipid fractions. AB - Fatty acid (FA) profile of plasma total lipids, phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG) were measured in 101 patients with advanced liver cirrhosis and in 44 age- and sex-matched healthy controls. Plasma levels of lipidic phosphorus, esterified cholesterol, and TG also were measured, and the unsaturation index (UI) was calculated for each fraction. Total plasma concentrations of saturated FA, linoleate, and polyunsaturated FA (PUFA) were lower in cirrhotics than in controls. This profile was also found in plasma levels of PL- and CE-associated FA. No detectable amounts of C20:3n9 were found in cirrhotic patients. Percent FA distribution of lipid fractions showed a lower percentage of linoleate and PUFA and a higher relative amount of saturated and monoenoic FA in cirrhotics than in controls. As a consequence, the UI of PL and CE was diminished in liver cirrhosis. Linoleate and PUFA deficiency was more marked in CE than in PL, as shown by the number of patients with values below the 5th percentile of the control group, suggesting an attempt to maintain the unsaturation of PL as the most important component of cell membranes. Hepatic failure, poor essential FA intake, and malnutrition are some of the possible etiologic factors for PUFA deficiency in cirrhosis. Their relative contribution to plasma FA abnormalities, as well as the clinical and pathophysiological consequences of PUFA deficit in cirrhotic patients, requires further investigation. PMID- 2252026 TI - Hemodynamic changes in splenic blood flow during and after distal splenorenal shunt. AB - The purpose of this study was to examine the hemodynamic changes of the spleen and the subsequent influence on the numbers of blood cells both during and 1 month after distal splenorenal shunt (DSRS) with splenopancreatic disconnection in 20 patients with portal hypertension. The intraoperative splenic blood flow, measured with an electromagnetic flowmeter, significantly increased after shunt insertion: the mean percentage increases within the splenic vein and artery were 60% (p less than 0.01) and 37% (p less than 0.05), respectively. The splenic venous blood flow, measured with a pulsed Doppler flowmeter, had not changed significantly 1 month postoperatively (676 +/- 501 to 540 +/- 306 ml/min). The WBC and platelet counts significantly (p less than 0.05 and p less than 0.01, respectively) increased 1 month postoperatively, whereas there was a small, but significant (p less than 0.05), decrease in RBC count. We concluded that splenic blood flow increases immediately after DSRS with splenopancreatic disconnection, but this increase may be only short term. The influence of the postoperative hemodynamic changes on blood cell count is uncertain. PMID- 2252025 TI - Comparison of two ascitic fluid culture methods in cirrhotic patients with spontaneous bacterial peritonitis. AB - The conventional method of ascitic fluid culture detects bacteria in only 50% of cirrhotic patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis (SBP). We have prospectively compared two ascites culture methods in cirrhotic patients with spontaneous bacterial peritonitis: 1) conventional (on chocolate agar, blood agar, Mac Conkay agar, and thioglycolate broth), and 2) modified [inoculation of 10 ml of ascites in a tryptic soy broth (TSB) blood culture bottle at the patient's bedside]. In a 21-month period, 70 episodes of SBP were diagnosed according to our criteria in 60 cirrhotic patients. Both culture methods were performed simultaneously. The conventional grew bacteria in 40 episodes (57%), whereas the modified grew bacteria in 54 episodes (77%), a significantly higher sensitivity (p = 0.0001). In 16 cases (23%), ascitic culture was negative by both methods. The mortality rate was higher among patients with culture-positive SBP than those with culture-negative SBP (46% vs 37%), but did not reach statistical significance. We conclude that ascitic fluid inoculated into a TSB blood culture bottle at the patient's bedside should be used routinely for ascites culture in cirrhotic patients. PMID- 2252027 TI - Pedunculated giant lipoma of the esophagus. AB - A patient with a giant lipoma of the esophagus presented with progressive dysphagia and odynophagia, fever, and recurrent melena. Two years previously, when the symptoms were less pronounced, it had been misdiagnosed as achalasia. After surgical removal of the lipoma, the patient became symptom free. PMID- 2252028 TI - Peritoneal mesothelioma: an unusual cause of esophageal achalasia. AB - Secondary esophageal achalasia due to malignancy is a rare condition; only 53 such cases have been reported to date. Sixty-two percent of the cases were due to gastric adenocarcinoma. Mesothelioma of the peritoneum is an uncommon neoplasm. The usual presenting symptoms are abdominal pain, abdominal mass, or abdominal distention. The patient we are reporting had peritoneal mesothelioma which presented with dysphagia and weight loss, in addition to the radiological and manometric picture of achalasia. Secondary achalasia was suspected clinically, and was confirmed by computed tomography and laparotomy. The diagnosis of peritoneal mesothelioma was made only by histopathological examination. We are not aware of any other report documenting the association of peritoneal mesothelioma and achalasia. PMID- 2252029 TI - Voluntary induction of transient lower esophageal sphincter relaxations in an adult patient with the rumination syndrome. PMID- 2252030 TI - Primary adrenal insufficiency: a new cause of reversible gastric stasis. AB - Primary adrenal insufficiency is known to cause a wide spectrum of sometimes severe upper gastrointestinal symptoms; however, it has not previously been shown to be the cause of reversible gastric stasis. We have documented such a case in which the symptoms and physiologic abnormalities associated with gastric stasis were reversed by steroid replacement. A follow-up radionuclide gastric-emptying study after physiologic steroid replacement showed complete normalization of gastric emptying. Although gastric stasis has long been suspected of being present with primary adrenal insufficiency, this represents the first case in which it has been documented, and so should be included in the differential diagnosis of patients presenting with chronic nausea and vomiting. PMID- 2252031 TI - Multifocal gastric carcinoma arising from hyperplastic and adenomatous polyps. AB - This paper is a presentation of the unusual case of a 61-yr-old woman operated on for multiple gastric cancers. Two of the cancers were found in the hyperplastic polyps and one in the adenoma. Apart from cancers that arose from these polyps, there were four separate polypoid or flat gastric carcinomas and three other hyperplastic polyps with no signs of malignancy, in this case. The presentation is followed by a detailed discussion focusing on the possible development of carcinoma in gastric hyperplastic polyps in view of the data from the literature. PMID- 2252032 TI - Synchronous diffuse well-differentiated lymphocytic lymphoma and gastric adenocarcinoma presenting as splenomegaly and iron deficiency anemia. AB - Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed. PMID- 2252033 TI - Reversal of chronic hepatic encephalopathy by colonic exclusion: poor correlation with blood GABA levels. AB - Previous studies have suggested that the inhibitory neurotransmitter gamma aminobutyric acid (GABA) is a key factor in the syndrome of portasystemic encephalopathy. We report the case of a patient with medically intractable portasytemic encephalopathy after portacaval shunt who had marked clinical improvement after creation of an end ileostomy. Plasma GABA and serum ammonia levels were measured before and after ileostomy. Although the clinical syndrome and the EEG improved markedly after the ileostomy, the plasma GABA levels remained markedly elevated. Preoperative and postoperative GABA levels were 865 and 633 pmol/ml, respectively (nl = 100-180 pmol/ml). Our findings confirm previous reports of the efficacy of colonic exclusion in patients with intractable portasystemic encephalopathy. However, our results conflict with the hypothesis that GABA itself is the key mediator of the syndrome. PMID- 2252034 TI - Primary leiomyoma of the liver. AB - A 30-yr-old woman with right upper quadrant abdominal pain was found to have a hepatic leiomyoma. This is the youngest patient in whom this rare tumor has been found. The diagnostic approach toward gastrointestinal leiomyomata is emphasized, including the role of immunohistochemistry. PMID- 2252035 TI - Hormonal therapy for bleeding from angiodysplasia: chronic renal failure, et al?? PMID- 2252036 TI - Variceal bleeding and beta-blockade: permutation on the theme? PMID- 2252037 TI - Taylor intragastric balloon. PMID- 2252038 TI - Trial of Taylor intragastric balloon. PMID- 2252039 TI - Hospitalization decision in patients with community-acquired pneumonia: a prospective cohort study. AB - PURPOSE: To identify a low-risk subset of patients with community-acquired pneumonia that could safely be treated in the ambulatory setting; and to assess how clinicians make the hospitalization decision. PATIENTS AND METHODS: We performed a prospective, observational study of 280 ambulatory and hospitalized adults with clinical and radiographic evidence of pneumonia. Patients were followed to assess all potential morbid complications and 6-week mortality. Physicians responsible for managing these patients were surveyed to assess the reasons for treating in a hospital or ambulatory setting and the therapies that dictate hospitalization. RESULTS: Sixty-one percent (170 of 280) of patients did not have an indication for admission at presentation using modified Appropriateness Evaluation Protocol criteria (a severe vital sign abnormality, alteration in mental status, suppurative complication, arterial hypoxemia, severe laboratory abnormality, or an acute coexistent medical problem requiring admission independent of the pneumonia). Among these 170 patients, 38% had a complicated course defined as death within 6 weeks, development of a new suppurative or medical complication due to pneumonia, intensive care unit admission, persistent fever or use of intravenous fluids or oxygen beyond 3 days, hospitalization lasting more than 3 days, or subsequent hospitalization in patients initially treated in the ambulatory setting. Five predisposing factors for a complicated course were identified in logistic regression models. The odds ratio for age more than 65 years was 2.7; for comorbid illness, 3.2; for temperature more than 38.3 degrees C (101 degrees F), 4.1; for immunosuppression, 12.0; and for a high-risk etiology, 23.3. The risk of a complicated course increased linearly with the number of risk factors, from 12% with none to 100% with four or more factors (p less than 0.001). Physicians most often relied on the general clinical appearance of the patient when making the triage decision, and most commonly cited intravenous antibiotics and chest physical therapy as treatments requiring hospitalization. CONCLUSIONS: If validated, our findings could improve physicians' assessment of prognosis, and may identify a low-risk subset of patients with community-acquired pneumonia who could safely be managed in the ambulatory setting. PMID- 2252040 TI - Ofloxacin treatment of Chlamydia pneumoniae (strain TWAR) lower respiratory tract infections. AB - PURPOSE: Limited data suggest that tetracycline or erythromycin is the antibiotic of choice for treating Chlamydia pneumoniae infection, but they are not always effective or well tolerated. Because the fluoroquinolone ofloxacin is effective for Chlamydia trachomatis infections, we investigated its role in treating C. pneumoniae infections. PATIENTS AND METHODS: Eighty-seven patients were enrolled in a randomized trial of antibiotic therapy for acute lower respiratory tract infections. The patients were randomly assigned to oral treatment with either ofloxacin (400 mg twice a day) or erythromycin (400 mg four times a day) for 10 days. Frozen acute and convalescent serologic specimens were tested for TWAR antibody by microimmunofluorescence. Susceptibility testing of C. pneumoniae to ofloxacin was also performed. RESULTS: Four patients who received ofloxacin were retrospectively identified as having C. pneumoniae pneumonia (two) or bronchitis (two). Within 2 weeks of starting ofloxacin therapy, all were cured or markedly improved. The minimum inhibitory concentrations of ofloxacin for three previously isolated clinical strains of C. pneumoniae were determined to be 1.0 to 2.0 micrograms/mL, well within the achievable serum levels (3 to 5 micrograms/mL) with ofloxacin therapy. CONCLUSION: Ofloxacin may be an effective alternative antibiotic treatment for C. pneumoniae respiratory infections. PMID- 2252041 TI - Failure to limit quantities of benzodiazepine hypnotic drugs for outpatients: placing the elderly at risk. AB - PURPOSE: The long-term use of benzodiazepine hypnotics by the elderly is associated with serious side effects, and prescriptions of large quantities of these agents allow such use. Therefore, we determined the quantities of these agents prescribed to outpatients in our Veterans Administration teaching hospital, and the relationship of patient age to total number of doses prescribed per prescription. PATIENTS AND METHODS: Pharmacy and patient records related to 655 consecutive prescriptions for triazolam (Halcion) and flurazepam (Dalmane) were reviewed. Only 266 (41%) of the prescriptions were for 30 or fewer doses, while 178 (27%) were written for 180 or more doses. RESULTS: Thirty-six percent of prescriptions for patients aged 65 years or older were for 180 or more doses, compared with 24% for those aged 45 to 64 years old, and 16% of the prescriptions for patients less than 45 years old (p less than 0.0001). In a multivariate analysis controlling for six other factors related to the total number of doses prescribed, patients aged 65 years or older were still more likely to receive a prescription for 180 or more doses (relative risk 1.9, 95% confidence interval 1.3, 2.8). CONCLUSION: We conclude that inappropriately large quantities of benzodiazepine hypnotics were commonly prescribed, and that patients aged 65 years or older were at greatest risk for receiving such prescriptions. PMID- 2252042 TI - Avascular necrosis of bone: a common serious complication of allogeneic bone marrow transplantation. AB - PURPOSE: To describe the incidence, presentation, clinical course, and management of avascular necrosis of bone following bone marrow transplantation, and to identify risk factors related to its development and outcome. PATIENTS AND METHODS: All patients developing avascular necrosis after transplantation between March 1974 and May 1988 were identified by means of the Minnesota Bone Marrow Transplant Database and hospital records and included in analysis. Of 902 consecutive patients undergoing bone marrow transplantation, 28 developed avascular necrosis of bone. RESULTS: Twenty-eight of 642 allogeneic transplant recipients (10.4% by product limit estimate) developed avascular necrosis compared to zero of 260 autologous transplant recipients. Symptoms developed 1 to 62 months (median 12 months) after transplantation. In the 28 patients a total of 91 joints were affected (mean 3.3 per patient, range one to eight joints). The hip joint was most often involved (64% of patients), followed by knee (61%), ankle (29%), shoulder (21%), and elbow (7%). Initial standard radiographs were negative in 13 patients, while in nine patients, technetium-99 scans and/or magnetic resonance imaging demonstrated changes of osteonecrosis before changes on routine radiographs. Almost all patients had received steroid prophylaxis and therapy for graft-versus-host disease (GVHD). We observed a significant correlation between the total cumulative dose of steroids and number of joints involved (p less than 0.01). A multivariate analysis (allogeneic transplant patients only) identified acute or chronic GVHD requiring steroid therapy (p = 0.003), and increasing age (p = 0.002) as significant and independent risk factors. Fourteen patients required surgery, including joint replacement in 11 patients. In six of six patients, hip core decompression failed to halt disease progression, and total hip arthroplasty was subsequently required. CONCLUSION: Avascular necrosis of bone is a frequent late complication of bone marrow transplantation, causing significant morbidity and often requiring surgery; diagnosis using conventional imaging techniques may be difficult and treatment remains inadequate. PMID- 2252044 TI - Major depression, panic disorder, and mitral valve prolapse in patients who complain of chest pain. AB - PURPOSE: Patients with chest pain but without angiographic evidence of significant atherosclerotic coronary artery disease (CAD) are often found to have other medical or psychiatric disorders, including mitral valve prolapse, panic disorder (PD), and major depressive disorder (MDD). The purpose of this study was to determine the degree of comorbidity between MDD/PD and mitral valve prolapse in a group of patients with non-CAD chest pain. PATIENTS AND METHODS: Patients referred for cardiac catheterization and coronary angiography for suspected CAD who were 70 years of age or younger and without other significant medical illnesses or cardiac complications were eligible for study. The first 100 patients who agreed to a psychiatric diagnostic interview were recruited. RESULTS: Forty-eight of the 100 patients were found to be without significant CAD. Forty-two percent of these patients, compared to 19% of the patients with significant CAD, were found to have either MDD, PD, or both. Eighty percent of the patients without CAD who had mitral valve prolapse also had either MDD or PD (p less than 0.006). CONCLUSIONS: The finding that mitral valve prolapse was significantly associated with MDD/PD has implications for the diagnosis and treatment of patients with non-CAD chest pain, and may explain why these patients complain of symptoms. PMID- 2252043 TI - Treatment with 13-cis-retinoic acid in transfusion-dependent patients with myelodysplastic syndrome and decreased toxicity with addition of alpha tocopherol. AB - PURPOSE: The purpose of this study was to determine the response and tolerance to long-term treatment using 13-cis-retinoic acid (13-CRA) in transfusion-dependent patients with the myelodysplastic syndrome (MDS) and to determine the effects of therapy on the natural history of the disease. PATIENTS AND METHODS: Sixty-six consecutive patients with transfusion-dependent MDS seen in a medical school hospital and outpatient clinic from 1981 to 1988 were studied. The first 21 patients were treated with 13-CRA alone and the next 45 patients with 13-CRA plus alpha-tocopherol (AT). We compared responses to and toxicities of therapy, rates of transformation, and survival from onset of therapy in 20 evaluable patients treated with 13-CRA alone and 43 patients treated with 13-CRA plus AT. RESULTS: Four patients responded (20%) at 4 to 8 months to 13-CRA alone, but this response was associated with considerable toxicity and resulted in cessation of therapy. Among the responders, only one continued therapy and is currently in remission, whereas three discontinued therapy because of toxicity and have had a relapse and died. In the 13-CRA plus AT group, we observed one prolonged complete remission and 10 partial remissions (26%), with a decrease in skin and constitutional toxicities by the addition of AT, which enabled the continuation of 13-CRA indefinitely. Although the response rates were similar in both groups, fewer patients (28% versus 60%) experienced progression to acute leukemia in the 13-CRA plus AT group than in the group receiving 13-CRA alone, who terminated treatment (p = 0.018). A twofold increase in median survival of the RA/RARS and RAEB/CMML patient groups was observed with 13-CRA plus AT but was not significant (p greater than 0.5). CONCLUSION: This study shows a 20% to 26% response rate to 13 CRA and suggests that 13-CRA, if given continuously, decreases the rate of progression or transformation to acute leukemia in patients with MDS. The addition of AT ameliorates the toxicity of 13-CRA and allows for long-term treatment with 13-CRA. Since the standard treatment for MDS is currently unsatisfactory, these findings indicate that longer treatment with a non-marrow suppressive agent such as 13-CRA is important, and further trials to determine the role of 13-CRA plus AT in combination with new recombinant growth factors in the therapy for transfusion-dependent MDS should offer a new approach to a disease common in the elderly population. PMID- 2252046 TI - Visit to the doctor. PMID- 2252045 TI - Aspirin in the primary prevention of angina pectoris in a randomized trial of United States physicians. AB - PURPOSE: The objective of this study was to examine the effect of low-dose aspirin (325 mg on alternate days) on the primary prevention of angina pectoris in the United States Physicians' Health Study. Despite a postulated role of platelets in atherogenesis and myocardial ischemia, the effect of chronic platelet inhibition on the development of clinical angina pectoris is unknown. SUBJECTS AND METHODS: The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial among 22,071 male physicians aged 40 to 84 years, free from previous myocardial infarction, stroke, and transient cerebral ischemia at entry, and followed for an average of 60.2 months. The 21,738 physicians who were also free from angina pectoris at baseline constituted the study population for the present analyses. RESULTS: During 106,652 person-years of follow-up, 331 patients with confirmed angina pectoris were diagnosed, 194 of whom underwent a coronary revascularization procedure (coronary artery bypass graft surgery or coronary angioplasty). As compared to participants assigned placebo, the relative risk of confirmed angina pectoris in the aspirin group was 1.10 (95% confidence interval [CI], 0.88 to 1.38). For coronary revascularization, the relative risk was 1.19 (95% CI, 0.88 to 1.59). After simultaneous control for other coronary risk factors in a proportional-hazards model, these relative risks remained near unity at 1.07 (95% CI, 0.84 to 1.36) and 1.11 (95% CI, 0.81 to 1.52), respectively. When the risks of angina pectoris were examined according to year of randomization in the trial, there was no pattern of increasing benefit with longer duration of treatment. CONCLUSION: These randomized trial data indicate that chronic platelet inhibition with low-dose aspirin for an average duration of 60.2 months does not reduce the incidence of angina pectoris. PMID- 2252047 TI - Hirsutism with virilization. PMID- 2252048 TI - Central nervous system epidermoid cyst: a probable etiology of Mollaret's meningitis. PMID- 2252050 TI - Conus medullaris syndrome resulting from Toxoplasma gondii infection in a patient with the acquired immunodeficiency syndrome. PMID- 2252049 TI - Recurrent aseptic meningitis secondary to intracranial epidermoid cyst and Mollaret's meningitis: two distinct entities or a single disease? A case report and a nosologic discussion. PMID- 2252051 TI - Plasma cell dyscrasia in a 15-year-old boy: case report and review of the literature. PMID- 2252052 TI - Fast-growing pericardial mass as first manifestation of intrapericardial teratoma in a young man. PMID- 2252053 TI - Biliary obstruction caused by epithelioid angiomatosis in a patient with AIDS. PMID- 2252054 TI - Anaphylactoid reaction after typhoid vaccination. PMID- 2252055 TI - Inclement weather, pneumothorax, and a cavitary apical infiltrate. PMID- 2252056 TI - Careers in academic medicine. PMID- 2252057 TI - Medical complications of cocaine. PMID- 2252058 TI - Coffee consumption and serum lipids. PMID- 2252059 TI - Varicella hepatitis or post-varicella Reye's syndrome? PMID- 2252060 TI - Use of the Role Checklist with the patient with multiple personality disorder. AB - A paucity of occupational therapy evaluation tools exists for use with patients with multiple personality disorder. The Model of Human Occupation (Kielhofner & Burke, 1980), particularly the volition and habituation subsystems within this model, proved useful for the identification of the many facets of patients with multiple personality disorder on a short-term treatment unit. The Role Checklist (Oakley, Kielhofner, Barris, & Richler, 1986), a tool derived from the Model of Human Occupation, was adapted for use with this population and was found to be beneficial in the identification of common goals held by most of the personalities of each patient with multiple personality disorder. The use of the Role Checklist is illustrated with a case example. PMID- 2252061 TI - Art and multiple personality disorder: an expressive framework for occupational therapy. AB - Patients with multiple personality and dissociative disorders have learned to create an alternate identity system, originally designed to protect them from experiencing the pain of inescapable, unrelieved trauma and abuse. The resulting amnesia and identity confusion cause significant dysfunction in daily living. Issues of trust and control are paramount, and occupational therapists are challenged with the task of engaging these patients in meaningful activity. Although these patients often avoid structured groups, they have generally been responsive to expressive art opportunities as an initial activity. This paper outlines an expressive framework by which occupational therapists can therapeutically manage the artwork behaviors of the patient with dissociative or multiple personality disorder. The material presented is based on clinical observation of more than a dozen patients with multiple personality disorder in various stages of recovery and of many persons with dissociative trauma who may have multiple personality disorder. These observations took place within an acute care, inpatient occupational therapy setting. Guidelines for the creation of a positive working alliance and therapeutic climate for self-expression are outlined, and a progressive model for the viewing of patients' art products is described. PMID- 2252062 TI - Occupational therapy with patients with multiple personality disorder: personal reflections. AB - Patients with multiple personality disorder are being admitted to acute care psychiatric units with increasing frequency. Occupational therapists have been confronted with setting treatment goals and designing interventions for this population with little information available in the occupational therapy literature. This paper describes how one therapist, the author, reviewed psychiatric and psychological literature on multiple personality disorder to delineate a role for occupational therapists who are working with this special population on an acute care psychiatric unit within the context of existing programs. PMID- 2252063 TI - Evolving educational practices in occupational therapy: the War Emergency Courses, 1936-1954. AB - The paper uses evidence collected from both written and oral history sources to present one approach to understanding the way in which educational practices evolved in occupational therapy. The paper introduces two fundamental positions regarding the nature, scope, and content of professional preparation for occupational therapists. For expediency, these viewpoints are labeled academicism and experientialism. This paper traces the interaction of these positions in the development and implementation of the War Emergency Courses. The implications for educational policy in occupational therapy arising from that program are also examined. PMID- 2252064 TI - Toward becoming one self. AB - I communicated often with the patient's psychologist during her last hospitalization. As the patient moves slowly toward integration, she and I remain in contact through correspondence and occasional lunch meetings. This friendly relationship provides a much-needed ongoing support system for the patient, which is provided by one who is familiar with her diagnostic picture. This paper has described early occupational therapy interventions with a patient whose condition has been newly diagnosed as multiple personality disorder. Skinner (1987) suggested that additional occupational therapy interventions be implemented as the patient improves. PMID- 2252065 TI - The sand tray technique in the treatment of patients with dissociative disorders: recommendations for occupational therapists. PMID- 2252066 TI - Understanding skepticism toward multiple personality disorder. PMID- 2252067 TI - Multiple personality disorder. PMID- 2252068 TI - Childhood sexual abuse and multiple personality disorder: emotional sequelae of caretakers. PMID- 2252069 TI - Multiple personality disorder: an overview. AB - Multiple personality disorder is understood today as chronic dissociative psychopathology that most often develops in response to severe abuse in childhood. The dissociative component is a manifestation of a defense mechanism out of control. The person with a biopsychological capacity to dissociate flees inward from overwhelming abuse or feared abuse. When continuing abuse perpetuates dissociations and they are chained by common affective themes, the foundations of multiple personality disorder are laid. Although the disorder has its roots in childhood, most patients are not diagnosed with this condition until 20 to 50 years of age. Many have received several prior, erroneous diagnoses of mental or physical disorders or both over a period of 7 or more years. Failure of diagnosis is an indication of the multiple factors that contribute to making this a covert disorder. Diagnosis and management begin at the same place: the establishment of trust and therapeutic alliance between patient and therapist. PMID- 2252070 TI - Child abuse as an antecedent of multiple personality disorder. AB - Until recently, few cases of multiple personality disorder were diagnosed in children. Today, the number of cases is increasing at an alarming rate and appears to be most closely associated with repeated sexual and physical abuse. This paper focuses on reports of childhood multiple personality disorder in the literature, the etiology of this disorder, family dynamics, the differences between childhood and adult multiple personality disorder, credibility problems in children, reasons for failure to diagnose multiple personality disorder in children, treatment, and signs and symptoms to look for in the clinical setting. PMID- 2252072 TI - Expressive therapy in conjunction with psychotherapy in the treatment of persons with multiple personality disorder. AB - This article examines the prevalence and complexity of multiple personality disorder as well as the contributions that psychiatry and occupational therapy make in its treatment. The value of activity is that it serves as a nonverbal mediator of communication. Activities are also useful in helping the therapist to obtain a patient's history, which is necessary for abreaction (i.e., the patient's reliving and recalling of the original abuse). Abreaction is a precursor to the integration of the abusive memories into the patient's current life. PMID- 2252071 TI - Clinical manifestations in persons with multiple personality disorder. AB - Occupational therapists are becoming more involved in the treatment of persons with multiple personality disorder. Occupational therapy literature concerning treatment of this group of patients, however, is sparse. Clinical manifestations of multiple personality disorder include common alter personalities with distinct roles and functions, age-related behavioral patterns, and physiological differences. By recognizing and understanding these differences and characteristics and their relationship to treatment goals, occupational therapists can better use their background in life roles and occupations to increase the functional daily living skills of patients with multiple personality disorder. PMID- 2252073 TI - Understanding and cooperation among alter and host personalities. AB - There is little occupational therapy literature that addresses the profession's efficacy in the treatment of persons with multiple personality disorder, yet the characteristics and complexity of this disorder render it one that can gain much from occupational therapy intervention. This paper examines the ways in which the occupational therapist can help in the treatment of patients with multiple personality disorder by introducing the alter personalities to each other, encouraging rapport among the personalities, and providing tasks that allow the alter personalities and the host to work together for mutual benefit. PMID- 2252074 TI - Considerations and techniques in the treatment of persons with multiple personality disorder. AB - Occupational therapy intervention with the patient with multiple personality disorder requires an understanding of the complex psychotherapeutic goals for the patient and of the process involved in resolution of the trauma that led to the development of multiple personality. The psychotherapeutic techniques of hypnosis and abreaction affect the provision of occupational therapy services. Hypnotic communication, particularly the use of ideomotor hand signals, often facilitates work with various alter personalities. Occupational therapists may use a developmental approach with both child and adult alter personalities and may also use projective techniques, self-care training, and role and task management techniques. Occupational therapy can act as a stabilizing force for the person with multiple personality disorder through the enhancement of function and competency during the psychotherapeutic process. PMID- 2252075 TI - Stature estimation in prehistoric Native Americans of Ohio. AB - In the present report we investigate stature estimation techniques in a sample of 64 (35 male, 29 female) prehistoric Native Americans from Ohio. Because living stature is unknown for these 64 individuals, we use Fully's (1956) anatomical method to provide the best estimates of living stature. In this method all osseous components of skeletal height are measured and soft tissue correction is added. Comparisons of regression equations commonly used for stature estimation in prehistoric Eastern Woodland Native American populations, but developed for East Asian and East Asian-derived populations (using lower extremity components), show that these commonly used equations consistently yield stature estimates 2 to 8 cm in excess of the best estimates from Fully's method. Based on the skeletal height measures of the 64 individuals in the present sample, we develop regression equations for the estimation of stature. These equations yield stature estimates virtually identical to estimates from Fully's method and may prove useful for stature reconstruction in other prehistoric Eastern Woodland Native American populations. PMID- 2252076 TI - Opportunity for natural selection among the Indian populations. AB - A critical review of data on opportunity for natural selection among the Indian populations has been made. These data on 96 populations were analysed according to regional, habitat, and socioeconomic backgrounds. The trends observed on the basis of these Indian data have been compared with worldwide data and data from industrialized nations. As in the industrialized nations, a gradual decrease in I(m) and I(t) is observed with improving socioeconomic and technological status in the Indian populations. The Indian situation is similar to that of the first phase in the modern demographic transition among the industrialized nations. PMID- 2252077 TI - Age estimation from cortical index of the human clavicle in northwest Indians. AB - The proportion of the cortical thickness to the total diameter of the bone (cortical index) was calculated in paired clavicles obtained from 128 male and 82 female medicolegal postmortem subjects who were apparently healthy prior to their accidental death. The ages of the subjects varied from 15 to 85 years. The clavicles were cut either horizontally or parasagittally, and measurements were taken at midclavicle. From the ages of 15 to 30 years, the cortical index increased. It decreased steadily thereafter, with an initial sharp decrease in the age group 31-40 years in both sexes. After the age of 40 years, this rapid decrease in the index continued in the females, but became slow and gradual in the males. Differences between left and right sides were statistically insignificant in both sexes (P greater than 0.05). However, the sexual differences were significant (P less than 0.01) in the age groups from 41 years onwards. PMID- 2252078 TI - Efficiency of cranial bilateral measurements in separating human populations. AB - A set of 31 nonconventional paired cranial measurements, as well as six conventional nonpaired measures, were taken on 266 skulls, representing two related populations: Bedouins of the Israeli Negev Desert and Bedouins of the Sinai. The data were subjected to univariate and discriminant analyses to determine the relative efficacy of paired vs. conventional measures in sorting individuals according to tribal and sex affiliation. It was found that paired measures have greater discriminatory power (87%) than conventional ones (47%) in terms of classifying individuals belonging to human isolates derived from a common ancestor and sharing similar environmental conditions. This greater discrimination attests to the value of the level of "developmental noise" (a measure provided by fluctuating asymmetry) in sorting human populations. Possible explanations are proffered for the above finding. PMID- 2252079 TI - Mass-to-surface area index in a large cohort. AB - Many biological and anthropological investigations have described the role between mass-to-surface area index (M/SA) and heat tolerance. No large M/SA database exists that can be used as a reference standard to interpret previous or future M/SA studies. This report presents the M/SA data of a large military cohort (1,170 males aged 17-54 years, 305 females aged 17-40 years). The effects of gender, ethnic group, and age on the distribution of M/SA, as well as the relationship between M/SA and other physical characteristics, were described. It was observed that the increases of M/SA with increasing age (over the 17-75 years category) were not significant. All descriptive characteristics (including M/SA) were different (P less than .001) between males and females. M/SA was not statistically different between ethnic groups among both males and females. These data may be utilized to compare the M/SA values of U.S. citizens to those of other ethnic groups and to identify those laborers or athletes who possess the greatest theoretical risk of heat intolerance. PMID- 2252080 TI - Sleep and arousal patterns of co-sleeping human mother/infant pairs: a preliminary physiological study with implications for the study of sudden infant death syndrome (SIDS). AB - The prevailing research design for studying infant sleep erroneously assumes the species-wide normalcy of solitary nocturnal sleep rather than a social sleeping environment. In fact, current clinical perspectives on infant sleep, which are based exclusively on studies of solitary sleeping infants, may partly reflect culturally induced rather than species-typical infant sleep patterns which can only be gleaned, we contend here, from infants sleeping with their parents--the context within which, and for well over 4 million years, the hominid infant's sleep, breathing, and arousal patterns evolved. Our physiological study of five co-sleeping mother-infant pairs in a sleep lab is the first study of its kind to document the unfolding sleep patterns of mothers and infants sleeping in physical contact. Our data show that co-sleeping mothers and infants exhibit synchronous arousals, which, because of the suspected relationship between arousal and breathing stability in infants, have important implications for how we study environmental factors possibly related to some forms of the sudden infant death syndrome (SIDS). While our data show that co-sleeping mothers and infants also experience many moments of physiological independence from each other, it is clear that the temporal unfolding of particular sleep stages and awake periods of the mother and infant become entwined and that on a minute-to-minute basis, throughout the night, much sensory communication is occurring between them. Our research acknowledges the human infant's evolutionary past and considers the implications that nocturnal separation (a historically novel and alien experience for them) has for maternal and infant well-being in general and SIDS research strategies in particular. PMID- 2252081 TI - Reliability of age at death in the Hamann-Todd collection: validity of subselection procedures used in blind tests of the summary age technique. AB - The blind test procedures used by Lovejoy et al., (Am. J. Phys. Anthropol. 68:1 14, 1985a) have been criticized because they used the Hamann-Todd collection as their known-age population. It has been suggested that variation within this sample was reduced by selection procedures designed to ensure accuracy of age at death. Powerful statistical tests for differences in dispersion of ages for pubic symphyseal stages were applied to comparisons between their core sample (N = 238) and those of a large autopsy-room collection used to develop the Suchey-Brooks System (N = 530). The variances in ages of the selected Hamann-Todd Sample are not reduced. The careful subselection of specimens has resulted in a valid statistical core sample for use in the development of aging methodologies. PMID- 2252082 TI - Femur/stature ratio and estimates of stature in mid- and late-Pleistocene fossil hominids. AB - In previous limited investigations of the human femur/stature ratio we (Feldesman and Lundy: Journal of Human Evolution 17:583-596, 1988; Feldesman et al.: American Journal of Physical Anthropology 79:219-220, 1989) have shown it to be remarkably stable across ethnic and gender boundaries. In this study we evaluate the femur/stature ratio in 51 different "populations" of contemporary humans (n = 13,149) sampled from all over the world. We find that the mean ratio of femur length to stature in these populations is 26.74%, with a very restricted range of variation. When we compare mean femur/stature ratios of males and females, there are no statistically significant differences. ANOVA performed on a naive grouping of samples into "whites," "blacks," and "Asians" indicates that there are significant racial differences (P less than 0.001). When we subject these groups to Tukey's HSD procedure (a post-hoc test), we find that "blacks" are responsible for the significant ANOVA, being significantly (P less than 0.005) different from the other ethnic groups. "Whites" and "Asians" are not significantly different (P = 0.067) under the conditions of this analysis, although all these racial comparisons may be suspect given the small sample sizes. We tested the efficacy of the ratio in three situations: predicting stature of repatriated white Vietnam veterans; predicting stature in a random sample of South African blacks (of known stature), and predicting the stature of a single Akka pygmy. In the first and third cases, the femur/stature ratio does better than the traditionally recommended regression equation, while in the second case the predictions from the femur/stature ratio are less accurate than from the appropriate regression equation. These results encouraged us to apply this ratio to mid- and late Pleistocene fossil hominids, where the choice of reference population for stature estimates continues to trouble workers. We estimated stature for a sizeable number of Homo erectus (HE), early Neanderthal (EN), Near Eastern Neanderthal (NEN), and early anatomically modern Homo sapiens (EAMHS) by using the simple relationship: stature (cm) = femur length (cm) * 100/26.74. Our results show that HE fossils are slightly taller on average than either EN or NEN samples, which do not differ significantly in stature, while EAMHS fossils are significantly taller than all three earlier groups. While these results are not surprising, our stature estimates for these fossils differ from currently published estimates based on sample-specific regression-based formulae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2252083 TI - The anatomy and histology of the inferior glenohumeral ligament complex of the shoulder. AB - The gross and histologic anatomy of the inferior glenohumeral ligament was studied in 11 fresh frozen cadaver shoulders. Arthroscopic observations of the joint capsule through the normal range of motion revealed that the inferior glenohumeral ligament is actually a complex of structures consisting of an anterior band, a posterior band, and an interposed axillary pouch. While these components of the inferior glenohumeral ligament complex were present in all 11 specimens, they were best demonstrated in some shoulders by placing the humeral head in internal or external rotation in varying degrees of abduction. Histologic examination of the joint capsule revealed that the anterior and posterior bands of the inferior glenohumeral ligament complex were readily identifiable as distinct structures comprised of thickened bands of well-organized collagen bundles. Although slight variations were noted in the attachment sites of the anterior and posterior bands to the glenoid, the inferior glenohumeral ligament complex was observed to attach to the humeral neck in one of two distinct configurations. A collar-like attachment, in which the entire inferior glenohumeral ligament complex attaches just inferior to the articular edge of the humeral head, was observed in six specimens. In the remaining five specimens, the attachment was in the shape of a "V," with the anterior and posterior bands attaching adjacent to the articular edge of the humeral head and the axillary pouch attaching at the apex of the "V" distal to the articular edge. The orientation and design of the inferior glenohumeral ligament complex supports the functional concept of this single structure as an important anterior and posterior stabilizer of the shoulder joint. PMID- 2252084 TI - Reconstruction of the anterior cruciate ligament using allogeneic tendon. Long term followup. AB - Eighty-four patients who underwent ACL reconstruction with fresh-frozen allogeneic tendon were reviewed and evaluated with subjective and functional rating scales, physical examinations, instrumented anterior drawer tests, isokinetic testing, and arthroscopy. The average followup was 57 months (range, 36 to 90 months) and the average age at operation was 22 years (range, 16 to 37 years). The subjective and functional results were rated as excellent in 48 patients (57%), good in 31 (37%), and fair in 2 (2%). Three patients (3%) experienced a retear of the ACL. Physical examinations and instrumented anterior drawer tests showed that satisfactory anterior stability was restored in 88% of the patients. Isokinetic evaluations demonstrated that the extension torque of the involved knee recovered to a slightly lower level than that of the controls, although the flexion torque recovered to a level equivalent to that of the controls. Arthroscopic evaluations revealed that the allografts were elaborately remodeled, viable, and taut. There was no sign of immunologic rejection at any time postoperatively. Additional extraarticular procedures, consisting of both pes anserinus transfer on the medial side and iliotibial band reinforcement on the lateral side, had no effect on the results. PMID- 2252085 TI - Pathologic synovial plica of the knee. Results of conservative treatment. AB - Observations of 136 cases of pathologic synovial plica of the knee were analyzed with regard to etiology, symptoms, and the results of conservative treatment. The results obtained with conservative treatment were good in 40% of cases, average in 20%, and poor in 40%. In our opinion, these results justify the treatment of this condition with physical therapy before proceeding with surgical correction. The objective of physical therapy was to decrease the compressive forces in the anterior compartment of the knee by increasing the structural flexibility of the flexor and extensor muscles. This increase in flexibility was obtained by instituting stretching exercises for the hamstrings, gastrocnemius, and quadriceps. PMID- 2252086 TI - Surgical correction of the snapping iliopsoas tendon. AB - Eighteen patients with 20 symptomatic hips underwent lengthening of the iliopsoas tendon for persistent painful snapping of this "internal" variety of snapping hip. We referred to the pathologic, painful snapping of the iliopsoas in the deep anterior groin as the "internal" snapping hip. This is in contrast to the more common and better-known "external" snapping that involves the greater trochanter and its overlying soft tissues. The results of our iliopsoas lengthening procedure are presented here. Lengthening of the iliopsoas tendon was accomplished by step cutting of the tendinous portion of the iliopsoas. The pathoanatomy of this poorly understood symptom complex was described in 1984 paper from this institution and is reviewed here. Iliopsoas bursography demonstrated a sudden jerking movement of the iliopsoas tendon between the anterior inferior iliac spine and iliopectineal eminence, synchronous with the patient's pain and often accompanied by an audible snap. The average preoperative duration of symptoms was 2.9 years, and the average length of postoperative followup was 25 months. All patients, except one, had a marked reduction in the frequency of snapping after tendon lengthening, and 14 of 20 hips had no snapping postoperatively. Of the six patients who had recurrence of snapping, all but one stated that this occurred much less frequently and was much less painful compared to the preoperative state. Two hips required reoperation. Postoperatively, only three patients complained of subjective weakness, and most patients were unlimited in physical activity with return to activities such as competitive football, pole vaulting, and long-distance running.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252087 TI - Secondary damage to the knee after isolated injury of the anterior cruciate ligament. AB - Between 1978 and 1984, we examined and performed arthroscopy on 1000 consecutive patients. Ninety-eight of the 1000 had isolated ACL damage. These cases do not include patients with initial ACL injuries combined with other intraarticular damage. Diagnosis was by physical and arthroscopic examination. Examination took place an average 13.6 months after injury. Of the 98 isolated ACL injuries, 56 were complete ruptures and 42 were partial ruptures. In most cases of partial rupture, the clinical diagnosis was wrong. "Meniscal damage" was the usual diagnosis in these cases; the true diagnosis was made only by arthroscopic examination. Thirty-four of the 98 patients with isolated ACL injuries (30 men and 4 women) developed further intraarticular damage. Of these 34, 20 had complete ACL rupture and 14 had partial ACL rupture. Treatment after primary injury included physiotherapy in all patients and bracing in those whose knee was unstable during daily activities. Reconstructive surgical procedures were not performed in those patients. The time lapse from the primary to the secondary injury varied from 1 month to 20 years, with an average of 28 months. The secondary damage was caused by a secondary injury that was mild (22 cases) or developed insidiously (12 cases). Five types of secondary damage were observed: partial ACL tears that became complete--11 cases; meniscal tear--8 cases; loosening and subluxation of the anterior horn of the medial meniscus--14 cases; and fracture or damage to the articular condylar cartilage, with or without bone involvement--11 cases. It should be emphasized that the secondary damages were at times combined. PMID- 2252088 TI - Shoulder arthroscopy: its role in evaluating shoulder disorders in the athlete. AB - We retrospectively reviewed 100 initial shoulder arthroscopies from a general sports medicine orthopaedic practice to determine if arthroscopy is helpful diagnostically and to see if specific lesions correlate well with specific diagnoses. Seventy-two percent of the patients in the review had glenoid labral tears. Ninety-two percent of patients who had a diagnosis of either recurrent anterior dislocation or recurrent anterior subluxation demonstrated a tear of the anterior inferior margin of the glenoid labrum. Sixty-eight percent of patients with a diagnosis of impingement demonstrated tears at the superior margin of the labrum. There was a significant difference between throwing and nonthrowing athletes. Partial rotator cuff tears were noted in 18 patients, the majority occurring in throwing athletes. Other abnormalities, such as degenerative joint changes and biceps tendon lesions, were also noted at the time of arthroscopy. A large number of glenoid labral tears found at the time of arthroscopy appeared to be associated with conditions other than instability, which may or may not affect the throwing athlete. There also appeared to be a high correlation between tears in the anterior inferior glenoid labrum and anterior instability. Arthroscopy enabled us to identify other significant information about the status of the biceps tendon or the undersurface of the rotator cuff. These are areas in which problems might otherwise have been missed. Degenerative changes of the articular surface, not apparent on plain radiographs, may also be better evaluated arthroscopically. PMID- 2252089 TI - Anterior cruciate ligament injury: evaluation of intraarticular reconstruction of acute tears without repair. Two to seven year followup of 155 athletes. AB - To evaluate the effectiveness of our treatment regimen, we retrospectively studied the surgically treated knees of 155 athletes, aged 15 to 42 years, who had sustained acute ACL tears. All were treated with ligament excision and intraarticular bone-patellar tendon-bone reconstruction followed by early motion with emphasis on full extension. The follow-up period ranged from 2 to 7 years. Of the 155 patients, 140 were available for final followup at a minimum of 2 years after reconstruction. The patients were evaluated by objective measures (KT 1000, Cybex, Lachman test, range of motion, and postoperative competition level) and subjective assessment scores (pain, swelling, stability, activity level, walking, stair climbing, running, jumping, or twisting). The subjective scores were tabulated for stability level, total score, and activity level. After the patients achieved full range of motion, the KT-1000 measurements at a 20 pound force revealed an average difference of 1.3 mm between the injured and noninjured knees. All but 3 of the 140 patients had a firm endpoint on the Lachman test, and the Cybex tests showed a mean hamstring strength of 98% and mean quadriceps strength of 90%. Sixty of the 69 varsity athletes who were eligible to play returned to preinjury competition level the following season. One had reconstruction failure and eight chose not to continue competition for academic reasons. The questionnaire score average was 92.7 (maximum, 100 points, normal athletic knee score 93.5). We concluded that the surgical procedure, with emphasis on early full extension postoperatively, achieved excellent results and provided a stable knee. PMID- 2252091 TI - Comparison of support provided by a semirigid orthosis and adhesive ankle taping before, during, and after exercise. AB - The purpose of this study was to compare the relative effectiveness of athletic taping and a semirigid orthosis in providing inversion-eversion range restriction before, during, and after a 3 hour volleyball practice. The effect of each support method on the subjects' vertical jumping ability was also assessed. Fourteen ankles were treated with both methods of support. Passive inversion eversion range of motion was measured on an ankle stability test instrument during five testing sessions: 1) before support, 2) before exercise, 3) 20 minutes during exercise, 4) 60 minutes during exercise, and 5) after exercise. The two-way analysis of variance and posthoc comparisons revealed maximal losses in taping restriction for both inversion and eversion at 20 minutes into exercise. The orthosis demonstrated no mechanical restrictive failure until before and after exercise comparisons were made, and then only eversion range of motion was compromised. Neither support system affected subjects' vertical jumping ability. These results suggest that the semirigid orthosis may be more effective than taping in providing initial ankle protection and in guarding against ligamentous reinjury. PMID- 2252090 TI - Anteromedial tibial tubercle transfer without bone graft. AB - We followed 30 patients for more than 2 years after anteromedial tibial tubercle transfer for persistent patellofemoral pain associated with patellar articular degeneration. Twelve of these patients were followed more than 5 years. We report 93% good and excellent results subjectively and 89% good and excellent results objectively. The quality of improvement was sustained in all 12 of the patients who were evaluated again after more than 5 years from surgery. When examined separately, 75% of those patients with advanced patellar arthrosis achieved a good result; none of these patients achieved an excellent result. Postoperative continuous passive motion has markedly reduced the incidence of stiffness. Serious complications such as compartment syndrome, infection, and skin slough were avoided completely in 51 consecutive cases. Patellofemoral contact pressure studies in five cadaver knees have shown that anteromedial tibial tubercle transfer can provide substantial reduction of patellofemoral contact stress while helping to balance medial and lateral facet pressures. This surgical procedure is mechanically and clinically successful for alleviating intractable pain related to patellar malalignment and articular degeneration. This procedure enables the majority of appropriately selected patients with malalignment and patellar articular degeneration to resume increased levels of activity with substantially diminished pain. PMID- 2252092 TI - Incidence of cervical spinal stenosis in professional and rookie football players. AB - Sagittal canal/vertebral body ratios were measured on cervical spine lateral radiographs of 124 professional football players and 100 rookie football players. A total of 894 levels were measured in 224 players. Thirty-two percent (40) of the 124 professional football players, and 34% of the 100 rookies had a ratio of less than 0.80 at one or more levels from C3 to C6. The 0.80 ratio has been considered indicative of cervical spinal stenosis. This is the first time that the incidence of spinal stenosis, as determined by Torg's ratio, has been demonstrated in a population of professional and rookie football players. Because one-third of this population has cervical spinal stenosis as determined by the Torg ratio, other factors should be considered in the evaluation of a player with a transient quadriplegic episode when making continued play decisions. PMID- 2252093 TI - Living with artificial grass: a knowledge update. Part 2: Epidemiology. AB - Part 2 of our study evaluated the effect of artificial grass on the athletes that play on it. In this section we have reviewed the epidemiological studies that have evaluated the influence that artificial grass has on the frequency and site of injury to American football players. From this review we have concluded that play and practice on an artificial surface is probably responsible for an increase in the relative risk of injury to the lower extremity of the participants. However, it is evident that more well controlled studies are necessary to completely clarify this issue. PMID- 2252094 TI - Arterial abnormalities of the shoulder in athletes. AB - Vascular lesions of the shoulder may be misinterpreted as one of the more familiar shoulder abnormalities by a treating physician. We are reporting on 13 athletes who were found to have symptoms related to compression of the subclavian or axillary artery or their tributaries. Nine were amateur or professional baseball pitchers. Severe arm fatigue or finger ischemia, secondary to embolization, were presenting symptoms. Arm fatigue was noted in all pitchers. After complete history and physical examination, including auscultation for bruits in functional positions, all athletes were evaluated by noninvasive tests (Doppler and Duplex scanning). Arteriography was performed with positional testing, recreating overhead activity, and complete radiographic visualization of the dye to the digital arteries. Two patients were found to have subclavian artery aneurysm. The remaining athletes were found to have compression of the subclavian artery beneath the anterior scalene muscle (five patients), the axillary artery beneath the pectoralis minor (two patients), both arterial segments (two patients), and one was found to have arterial compromise at the level of the humeral head. Branch artery compression was also noted. One pitcher occluded the posterior circumflex humeral artery with embolization to the digit. The two patients with subclavian aneurysms underwent saphenous vein bypass with cervical rib resection. All of the other athletes except one underwent resection of a 2 to 3 cm segment of the anterior scalene muscle or pectoralis minor muscles. All returned to their previous level of activity except one patient who developed impingement type symptoms and required acromioplasty. He is currently undergoing rehabilitation. Proper recognition of vascular compromise in the upper extremity of athletes is essential to avoid the catastropic complications of arterial thrombosis. PMID- 2252095 TI - Arterial abnormalities of the hand in athletes. AB - Vascular lesions of the hand may be seen in athletes exposed to repetitive blunt trauma. Thirteen athletes seen from 1983 to 1988 experienced symptoms related to hand ischemia. Nine were professional baseball catchers. The majority of patients complained of chronic symptoms, including cold hypersensitivity (four patients), finger numbness (one), finger coolness (three), and finger blanching (three). Two patients had acute symptoms with sudden posttraumatic hand ischemia with finger and palmar pain. Diagnosis was established by history and physical examination and confirmed by noninvasive testing. Testing included use of Doppler examination and cold tolerance examination with thermistors. Two athletes required angiographic evaluation because of severe ischemia and continuous pain. All patients in this group were managed nonoperatively. Those with chronic complaints were counseled regarding cold avoidance and instructed to increase their glove padding. The two patients with acute symptoms required vasodilator (papaverine chloride) infusion, followed by intravenous heparin and dextran. All baseball catchers returned to their sport with dissipation of symptoms. PMID- 2252097 TI - Injury patterns in Scottish heavy athletics. AB - As interest and participation in the athletics of Scottish-American Highland games has increased throughout the United States, the aim of this study was to define injury patterns and risk factors. Field events of modern track and field evolved in part from the seven events of the "heavy athletics." A retrospective and prospective study of 170 athletes with at least 3 years of experience was carried out over 10 years. There were 729 injuries, 60% of which involved the upper extremities and back. The incidence of injury was 42.9%; there was an injury exposure rate of 0.3 per 40 hours of competition or training. With appropriate instruction, a consistent weight program, and exercise, few injuries were serious. PMID- 2252096 TI - Stress fractures of the femoral neck in athletes. The consequence of a delay in diagnosis. AB - Twenty-three patients with stress fractures of the femoral neck were followed up at an average of 6.5 years after the injury. There were 16 recreational athletes and seven elite athletes. Most injuries (N = 15) occurred during running. The diagnosis was confirmed within 3 to 104 weeks (mean, 14 weeks) after the initial onset of symptoms. Sixteen of the patients were treated with internal fixation, the remaining seven were treated conservatively. Seven patients (30%) developed complications requiring major surgery. Five of these patients had Type 3 fractures (displaced) and four had been treated with internal fixation initially. The remaining two patients had Type 1 fractures (endosteal or periosteal callus without an overt fracture line); one was treated operatively and the other conservatively. Three patients developed avascular necrosis and two were treated by hip replacement. The third patient was treated with arthrodesis. Three refractures and one pseudarthrosis were treated by osteotomy. At followup, all elite athletes stated that they had to end their career as a result of the injury. Results were rated by the ability of the athlete to return to sports. There were 9 bad or fair results, 13 good, and 1 excellent result. No difference in activity level or subjective rating was observed between the surgically and conservatively treated group either preinjury or postinjury. The most important factor influencing the complication rate seems to be the type of fracture. The high incidence of displaced fractures (Type 3) could speculatively be caused by undiagnosed tension side stress fractures. If so, the delay in correct diagnosis may be disastrous. However, we could only objectively observe this in one of our cases. PMID- 2252098 TI - Chondroma. An unusual presentation of an extraarticular soft tissue mass about the knee. PMID- 2252099 TI - Lateral ankle instability associated with dislocation of the peroneal tendons treated by the Chrisman-Snook procedure. A case report and literature review. PMID- 2252100 TI - Amateur boxing in Denmark. PMID- 2252101 TI - Mesonephric remnants, hyperplasia, and neoplasia in the uterine cervix. A study of 49 cases. AB - Hyperplasia of mesonephric remnants in the uterine cervix is an unusual condition that is often misdiagnosed as adenocarcinoma. The rare mesonephric carcinoma can be confused with more common forms of cervical adenocarcinoma. We studied 49 specimens of cervix containing mesonephric remnants, or lesions derived from them, in women 21 to 72 (mean, 38) years of age. Four cases were classified as mesonephric remnants, 31 as lobular mesonephric hyperplasia, eight as diffuse mesonephric hyperplasia, two as mesonephric ductal hyperplasia, and four as mesonephric carcinoma. In the nonneoplastic cases, the lesion was unrelated to symptoms that resulted from excision of cervical tissue and, except in one case, did not produce a detectable mass. In two cases of carcinoma, the patient presented with bleeding; in one case, the patient presented with pelvic relaxation. The manner of presentation was not known in the fourth case of carcinoma. Twenty-eight patients with mesonephric remnants or hyperplasia underwent hysterectomy; 15 had a cone biopsy; one underwent excision of the cervical stump; and one had only a cervical biopsy. None of these patients has had a recurrence. All four patients with carcinoma had a hysterectomy; three of them died of carcinoma 2 years and 10 months, 7 years, and 9 years after diagnosis, respectively. Correct classification of mesonephric lesions is imperative for appropriate patient management. PMID- 2252102 TI - A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation. AB - Based on a clinicopathologic study of 34 patients with biopsy-confirmed diffuse pulmonary hemorrhage (DPH), we present an approach to the differential diagnosis of DPH with attention to histologic features such as capillaritis and the importance of laboratory tests such as anticytoplasmic autoantibodies (ACPA). The following DPH syndromes were encountered: antibasement membrane antibody (ABMA) disease (four cases); idiopathic pulmonary hemorrhage (four cases); Wegener's granulomatosis (WG) (five cases); probable WG (six cases); systemic necrotizing vasculitis otherwise unclassified (three cases); systemic lupus erythematosus (two cases); rheumatoid arthritis (one case); seronegative juvenile rheumatoid arthritis (one case); IgA nephropathy (one case); idiopathic glomerulonephritis (two cases--one with and one without immune complexes); and unclassified pulmonary-renal syndromes (five cases). Capillaritis was found in lung biopsy samples from 30 of the 34 patients (88%) and included patients with every type of DPH syndrome. Serologic testing for ACPA was useful in the diagnosis of WG. Identification of ABMA in the serum, kidney, or lung was the defining feature for the diagnosis of ABMA-mediated disease. Subclassification of the cases could not be done solely on histologic grounds except for cases of WG that showed granulomatous inflammation, foci of necrosis, or vasculitis. Classification of the remaining cases required correlation with (a) clinical and laboratory data; (b) biopsy samples from other sites such as the kidney, nasal sinuses, or skin; and (c) results of immunofluorescence or electron microscopy of kidney or lung biopsy samples. PMID- 2252103 TI - bcl-2 gene rearrangement in salivary gland lymphoma. AB - There is a wide spectrum of lymphoid hyperplasias and neoplasias that may arise in salivary gland tissue. Some lesions arise in the extranodal mucosal-associated lymphoid tissue (MALT) located in the salivary gland; others arise within the lymph nodes embedded in the gland parenchyma. It is difficult to distinguish the site and cell of origin in many salivary gland lymphoid lesions, but recent advances in the identification of specific gene rearrangements in lymphomas corresponding to normal follicular center cells have provided a molecular marker for these tumors. The genes involved are the immunoglobulin heavy chain gene (located on chromosome 14) and the blc-2 gene (located on chromosome 18). This specific chromosomal translocation [t(14;18)] has been sought in extranodal lymphomas of skin, stomach, and intestine. To date, primary lymphomas in these sites have lacked the t(14;18) translocation. We investigated the t(14;18) using molecular techniques in a series of morphologically and immunophenotypically defined malignant non-Hodgkin's lymphomas presenting in the salivary gland. Of the seven cases we examined, three had molecular evidence of a t(14;18) translocation. All three lesions had a nodular growth pattern. The four cases lacking bcl-2 rearrangement had diffuse growth patterns. In addition, all four bcl-2 germline cases had morphologic or clinical findings consistent with a MALT origin. In contrast to the data published to date for primary lymphomas of the stomach, skin, and intestine, our findings indicate that salivary gland lymphomas frequently contain bcl-2 gene rearrangement. In addition, there appear to be differences in the clinical findings of bcl-2 rearranged and bcl-2 germline salivary gland lymphomas. PMID- 2252104 TI - An immunohistochemical study of thymic epithelial tumors. III. The distribution of interdigitating reticulum cells and S-100 beta-positive small lymphocytes. AB - We report an immunohistochemical study of the distribution and number of interdigitating reticulum cells (IDC) and S-100 beta-positive small lymphocytes (S-100 beta + lymphocytes) in 53 thymomas and 11 thymic carcinomas. All 53 thymomas showed the presence of IDC in the tumor parenchyma. In most cases of predominantly lymphocytic and mixed-type thymoma, IDC clustered in areas, that corresponded to locations that had medullary differentiation and contained accumulated mature lymphocytes. By contrast, in most of the predominantly epithelial-type thymomas, IDC were scattered rather than forming clusters. The distribution and number of IDC were correlation with the histological type of thymoma but not with invasiveness. In thymic carcinomas, IDC were scattered in tumor nests. In 47 of the 53 thymomas (89%), infiltrating S-100 beta + lymphocytes were readily recognized. The remaining six cases without S-100 beta + lymphocytes were noninvasive thymoma. We conclude that the degree of S-100 beta + lymphocyte infiltration is correlated with the stage of thymoma and may be a marker of thymoma malignancy. PMID- 2252105 TI - Nucleolar organizer regions (NOR) in hyperplastic and neoplastic prostate disease. AB - Nucleolar organizer regions (NOR) are DNA loops encoding ribosomal RNA production. Detectable by the argyrophilia (AgNOR) of associated proteins, AgNOR numbers correlate with growth fraction and may have diagnostic and prognostic utility in human tumors. Because nucleolar size is important in the diagnosis of prostate carcinoma, we compared AgNOR counts in benign, atypical, and malignant prostate lesions and correlated them with nucleolar diameter. We counted AgNOR in benign prostatic hyperplasia, atypical adenomatous hyperplasia, intraductal dysplasias, and carcinomas of various Gleason grades. The mean AgNOR count per nucleus for benign prostatic hyperplasia nuclei was 4.51; for atypical adenomatous hyperplasia, 5.64; for intraductal dysplasias, 7.35; for carcinoma of Gleason grades 2 + 3, 8.87; and for carcinoma Gleason grades 4 + 5, 10.42. Counts in the carcinomas and intraductal dysplasias were significantly different from those of benign prostatic hyperplasia. Mean AgNOR counts of the carcinomas and intraductal dysplasias did not overlap with those of benign prostatic hyperplasia, suggesting that intraductal dysplasia shares more with carcinoma than benign prostatic hyperplasia. Nucleolar diameters increased from benign prostatic hyperplasia to atypical adenomatous hyperplasia, intraductal dysplasias, and the carcinomas, correlating with increasing AgNOR counts. Nucleolar diameters in the carcinomas were significantly different than those of benign prostatic hyperplasia; those in intraductal dysplasias were not. Our findings suggest that AgNOR counts are superior to nucleolar diameters alone in separating intraductal dysplasias from benign prostatic hyperplasia but provide no additional information in diagnosing carcinoma. PMID- 2252106 TI - Dermatofibroma extending into the subcutaneous tissue. Differential diagnosis from dermatofibrosarcoma protuberans. AB - When dermatofibromas are composed predominantly of fibroblasts and extend into the subcutaneous tissue, it may be difficult to distinguish them from dermatofibrosarcoma protuberans. Because the patterns of extension of dermatofibroma have not been well characterized, we studied 185 cases of the fibrous variant of dermatofibroma with extension into the subcutaneous tissue and 40 cases of dermatofibrosarcoma protuberans. Dermatofibromas had two main patterns of extension into subcutaneous tissue. One pattern, seen in 133 of 185 cases (72%), consisted of irregular extension into the subcutaneous tissue in a vertical or radial fashion, predominantly along the septa, which appeared wedge shaped. The other pattern, seen in 52 of 185 cases (28%), showed a smooth and well-demarcated deep margin that bulged into the subcutaneous tissue. Dermatofibrosarcoma protuberans also had two main patterns of extension into the subcutaneous tissue. In one pattern, seen in 12 of 40 cases (30%), slender spindle-shaped cells extended along septa and between fat cells in a classic honeycomb or lacelike pattern. The other pattern observed in 24 of 40 cases (60%) exhibited a distinct multilayered pattern in which the bundles of slender spindle shaped cells showed a predominantly parallel orientation to the skin surface. In four cases (10%), a mixture of both patterns was present. We conclude that the patterns of extension of dermatofibroma into the subcutaneous tissue are different from the patterns of dermatofibrosarcoma protuberans. PMID- 2252107 TI - Malignant thyroid hemangioendothelioma. PMID- 2252108 TI - Papers of the Southwestern Surgical Congress. Proceedings of the 42nd annual meeting. La Quinta, California, April 22-25, 1990. PMID- 2252109 TI - The operation was a success, but.... PMID- 2252110 TI - Edgar J Poth lecture. Pathogenesis, diagnosis, and treatment of thrombosis. AB - Thrombosis and its major sequela, embolism, continue to contribute significantly to morbidity and mortality, both as primary disorders and as complications of other systemic systems. The understanding of the etiology of thromboembolism and the role of platelets, endothelium, and the plasma proteins in the development of thrombotic disorders has recently improved. Other blood cells, in particular neutrophils, have been suggested as possible mediators of thrombosis in clinical disorders characterized by decreased capillary blood flow. Newer imaging techniques such as duplex scanning have improved the accuracy and ease of diagnosis. Thrombolytic therapy is a more physiologic approach to the management of thrombosis, but its role is limited by systemic fibrinolysis. The development of fibrin-specific agents and better delivery techniques in combination with thromboembolectomy and anticoagulation should improve the management of patients with thrombosis. PMID- 2252111 TI - The "all-autogenous" tissue policy for infrainguinal reconstruction questioned. AB - In 33% of patients referred for infrainguinal reconstruction for limb-threatening ischemia (mean preoperative ankle-arm index [AAI] = 0.26), no suitable autogenous reconstruction was possible. In 40% of cases, intraoperative pre-bypass contrast arteriography was necessary to identify a graftable tibial or pedal artery. The results of polytetrafluoroethylene (PTFE) and autogenous bypasses were compared after 1 to 3 years. After 1 year, patency was 85% and 67% for autogenous and PTFE bypasses, respectively. Limb salvage was 90% for autogenous bypass and 70% for PTFE bypass. Cumulative patency rates at 3 years were 80% for autogenous and 57% for PTFE grafts. Graft surveillance with duplex scanning and AAI was valuable in detecting failing grafts. For both types of reconstruction, secondary procedures were required to maintain patency. We attribute the excellent results with PTFE in part to long-term aspirin and warfarin therapy. In cases of combined superficial femoral and severe infra-popliteal occlusive disease, PTFE bypass is an excellent alternative when no autogenous conduit is available. PMID- 2252112 TI - In vitro and in vivo evaluation of intraluminal ultrasound in normal and atherosclerotic arteries. AB - This study evaluated the dimensional and morphologic precision of arterial images obtained using intraluminal rotating A-scan ultrasound catheters [5.0F (30 mHz) and 8.0F (20 mHz)]. Dimensions of in vitro ultrasound images from human arteries (eight normal and nine arteriosclerotic) were compared with those from histologic sections of the vessels. In addition, in vivo ultrasound studies (23 normal and 22 arteriosclerotic) of canine femoral arteries were compared with luminal dimensions obtained from angiograms of the vessels. The correlation of in vitro ultrasound images to luminal diameters (n = 22, r = 0.96), adventitial diameters (n = 19, r = 0.83), and wall thickness (n = 19, r = 0.68) in normal human vessels was significant (p less than 0.05). In vitro measurements of images and histologic specimens from human atherosclerotic arteries also correlated significantly (p less than 0.05) with luminal diameters (n = 27, r = 0.91), adventitial diameters (n = 24, r = 0.60), and wall thickness (n = 24, r = 0.62). Morphologically, in vitro images of the wall of normal human arteries had a concentric laminated appearance and atherosclerotic vessels had patchy echodense and echolucent areas. In vivo studies showed significant correlation of diameters for both normal (n = 16, r = 0.91, p less than 0.05) and arteriosclerotic (n = 16, r = 0.57, p less than 0.05) canine arteries compared with luminal dimensions measured from uniplanar angiograms. We conclude that rotating A-scan intraluminal ultrasound accurately defines both normal and atherosclerotic arterial wall morphology and dimensions. This technology may be valuable for intravascular guidance of angioplasty devices by identifying the location and consistency of lesions. PMID- 2252113 TI - Surgical complications of continuous ambulatory peritoneal dialysis. AB - Surgical experience with 260 consecutive patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis (CAPD) at one medical center from 1980 to 1989 is reviewed. Patients received CAPD for a mean of 24.2 months (range: 3 days to 91 months). Catheter longevity consistently improved in all but 1 year from 1984 to 1989, as did exit-site and tunnel infections. Of 311 catheters inserted, 151 (49%) required removal, of which 111 (74%) were attributed to peritonitis. Cumulative patient survival was 80%, 60%, and 53% at 1, 2, and 3 years, respectively. Diabetic patients had statistically significant lower survival rates. Additional complications including catheter leakage, catheter malposition, catheter obstruction, and abdominal wall hernias were negligible. Although CAPD is not free from serious complications, our data show remarkable improvement since 1980 in catheter longevity, hospital stay, and infection rates. PMID- 2252114 TI - Ethanol diffuses across the gastric muscle wall. AB - Ethanol inhibits the electrical and mechanical activities of gastric smooth muscle, but only at concentrations higher than can be provided by serum delivery. We speculated that the ethanol concentration in the gastric wall may exceed plasma levels by direct diffusion across the mucosa and through the muscle layers. A model of acute ethanol ingestion was created by partitioning the stomachs of three dogs with a surgical stapling device and instilling carbon 14 (14C)-labeled ethanol into the proximal segments. The flux of ethanol was traced by counting 14C in serial sections of the gastric wall. A mucosa-to-serosa gradient of 14C activity was established. The data indicate that direct diffusion from the mucosal surface will produce dramatically higher concentrations of ethanol in gastric muscle than would be anticipated from serum levels alone. PMID- 2252115 TI - Acute appendicitis in the pregnant patient. AB - Acute appendicitis is the most common surgical problem in pregnancy requiring emergent intervention. To establish a contemporary patient profile and formulate an effective management strategy, a retrospective review was conducted of 84 pregnant patients who underwent laparotomy with a preoperative diagnosis of acute appendicitis. Gestational stage at presentation included the first trimester in 27 patients (32%), the second trimester in 37 patients (44%), the third trimester in 13 patients (16%), and the puerperium in 7 patients (8%). Fifty-four patients (64%) had pathologically proven acute appendicitis; the incidence did not vary by trimester. Other intra-abdominal conditions were detected in 15 patients (18%). There were no significant differences between patients with positive and negative laparotomies (or among trimesters) regarding frequency of presenting symptoms and signs or laboratory results. Operation occurred within 24 hours of symptom onset in 19 of 54 (35%) instances of proven acute appendicitis. Perforation occurred in 23 of 54 patients (43%), all of whom had symptoms exceeding 24 hours (p less than 0.0005). Five instances of perinatal death and one case of extreme perinatal morbidity were associated with negative laparotomies; only one of these was attributed to operation itself. No adverse long-term maternal morbidity or mortality occurred. Wound infection developed in seven cases of acute appendicitis (six perforated) and two negative explorations. We conclude that (1) gestational physiologic changes obscure the accurate diagnosis of acute appendicitis; (2) the natural history of acute appendicitis is not affected by trimester of presentation; and (3) adverse sequelae of acute appendicitis are obviated by prompt operative exploration and prevention of appendiceal perforation. PMID- 2252116 TI - Early detection of myocardial contusion and its complications in patients with blunt trauma. AB - Myocardial contusion remains an elusive clinical entity, which consumes a disproportionate amount of scarce and expensive critical care resources for the purpose of cardiac monitoring. This study attempts to define a group of patients at high risk who can be identified from the available data present at the time of admission. All patients admitted with the suspicion of a myocardial contusion over a 3-year period were retrospectively studied. The records were examined for history, physical findings, electrocardiographic (ECG) results, creatine kinase levels, Injury Severity Score (ISS), and echocardiographic findings. A diagnosis of a myocardial contusion was made if patients had an ECG consistent with acute injury, increased creatine kinase-MB, or an abnormal echocardiogram consistent with acute injury. Patients were stratified into two groups: Group 1 patients satisfied the criteria for a myocardial contusion and Group 2 patients lacked sufficient evidence to substantiate this diagnosis. The records were then examined for the presence of factors available in the emergency room that might be predictive of a myocardial contusion or its complications. A total of 88 patients were evaluated; 27 of these were found to have a myocardial contusion (Group 1) with 61 patients placed in Group 2 (no myocardial contusion). Group 1 patients had an abnormal admission ECG (p less than 0.05), and an ISS greater than or equal to 10 (p less than 0.05). Multivariate analysis identified two factors predictive of a myocardial contusion: an abnormal ECG and an ISS greater than 10. When these two predictors were absent, the probability of a myocardial contusion was 1%. No predictors of a complication of a myocardial contusion were identified. These data suggest that a combination of easily obtained variables in the emergency department can be used to select a patient population at high risk for myocardial contusion. Prospective evaluation of these variables is necessary. PMID- 2252117 TI - Balloon catheter tamponade in cardiovascular wounds. AB - From 1980 to 1990, operative balloon catheter tamponade was used in 12 patients with cardiac or vascular injuries from penetrating wounds. In nine patients, a balloon catheter was passed into a bleeding site through a bullet track or proximal artery and inflated with saline or radiologic dye. In two of these patients, the proximal balloon catheter was folded on itself, tied in that position, and left in the patient permanently. In the other seven patients in this group, the balloon catheter was attached to a three-way stopcock and left temporarily inflated postoperatively. These patients were then observed in the intensive care unit for 3 to 4 days, at which time the balloon was withdrawn. Eight of nine patients survived without recurrent hemorrhage after removal of the balloon catheter, while one patient with a Fogarty balloon placed in the carotid siphon died of a cerebral infarction. Balloon catheter tamponade was also used on a temporary basis in one patient with a posterior cardiac wound and in one patient with an anterior stab wound of the inferior vena cava at the renal veins, whereas in two patients with high cervical arteriovenous fistulas, one had permanent placement of the balloon catheter while the other had temporary placement. One of the latter patients also had acute hemorrhage. Although all four patients survived, one of the patients with a fistula developed a recurrence and another required two separate operative procedures for correct placement of the balloon to cure the fistula. PMID- 2252118 TI - Trend toward nonoperative management of splenic injuries. AB - Treatment of splenic injuries has evolved over the past decade to reflect more effort to conserve function of the spleen. Records of 169 patients admitted over a 6-year period were identified as documenting the treatment of splenic injuries. We collected data regarding patient age, gender, degree of hemodynamic stability, number of units of blood required, severity of splenic injury, Injury Severity Score, and results of treatment. There were 143 adults (age greater than 16 years) and 26 pediatric patients (age less than 17 years), with mean age in the 2 groups of 31.6 and 11.4 years, respectively. Males comprised 72% of the group, and blunt injury occurred in 154 of the 169 patients. In the adults, splenectomy, splenorrhaphy, laparotomy without operative treatment of the spleen, and nonoperative management were observed 48%, 30%, 14%, and 8% of the time and in the pediatric group 31%, 27%, 19%, and 23% of the time, respectively. By using operative splenic repair techniques and increased use of nonoperative management, the splenic salvage rate has increased in the last 6 years from 41% to 61% without an increase in morbidity and mortality. Incidence of spleen salvage correlated with severity of spleen and overall injury and cardiovascular stability. PMID- 2252119 TI - Open versus closed diagnostic peritoneal lavage in the evaluation of abdominal trauma. AB - Two hundred forty-two patients underwent diagnostic peritoneal lavage (DPL) over a 12-month period. One hundred sixteen patients (48%) were randomized to an open lavage technique and 126 (52%) to a percutaneous (closed) guide wire procedure. The closed procedure required an average of 16 minutes to complete with one operator, whereas the open method required two operators and an average time of 26 minutes (p less than 0.001). Technical complications occurred in 31 patients undergoing closed lavage (25%) and 4 patients undergoing open lavage (3%) (p less than 0.01). Fifty-eight percent of the closed lavage complications were related to fluid return and 42% to guide wire placement. All the open lavage complications were caused by inadequate fluid return. These data do not support the initial use of percutaneous lavage. The open technique is favored and certainly used when the closed method fails or when direct visualization of the peritoneal cavity is indicated. Physicians involved in the management of abdominal trauma must be familiar with both methods of DPL. PMID- 2252120 TI - Community hospital carotid endarterectomy in patients over age 75. AB - We compared the prevalence of stroke and death in 133 patients aged 75 and older in whom 170 carotid endarterectomies were performed with that in 501 patients less than age 75 in whom 640 carotid endarterectomies were performed. There were three strokes (2%) in patients aged 75 and older and nine strokes (1%) in younger patients (p = 0.7). There were 8 deaths (5%) in patients aged 75 and older and 14 deaths (2%) in younger patients (p = 0.1). After controlling for the possible confounding effects of diabetes, prior stroke, history of angina, prior carotid artery disease, previous vascular surgery, history of myocardial infarction, preoperative hypertension requiring medication, and female gender, a logistic regression model showed that patients aged 75 and older were no more likely to have a stroke or death than patients under age 75. We conclude that age alone is not a contraindication to the safe performance of carotid endarterectomy in the community hospital. PMID- 2252121 TI - Current status of duplex Doppler ultrasound in the examination of the abdominal vasculature. AB - Duplex Doppler ultrasound has come to play a central role in the diagnosis of a broad spectrum of vascular diseases such as carotid artery occlusive disease and deep vein thrombosis. The role of duplex Doppler in the evaluation of intra abdominal vascular disease remains unclear. This article summarizes the current status of duplex scanning in the investigation of the mesenteric arteries, the renal arteries, and the portal venous system. The examination is technically demanding, operator-dependent, time-consuming, and frequently unsatisfactory due to bowel gas, obesity, complex anatomy, or postoperative alterations in the normal anatomic patterns. Its advantages reside primarily in the absence of toxicity and in the generation of physiologic as well as anatomic information. In centers with the proper instrumentation and a skilled technician, duplex examination can be useful in the diagnosis and management of abdominal vascular disease and avoids the inherent dangers of contrast angiography. PMID- 2252122 TI - Choledochotomy for calculous disease in the elderly. AB - To determine the risk of operations on the biliary tract in the elderly, we retrospectively examined 56 patients 80 years of age or older undergoing choledochotomy for calculous disease and compared their outcomes with those of a contemporary group of 257 patients undergoing similar surgery. Thirty of 56 elderly patients (54%) required urgent surgery for acute cholangitis, acute cholecystitis, or obstructive jaundice (serum bilirubin greater than 5 mg/dL), compared with 97 of 257 younger patients (38%) (p = 0.029). Mortality in elderly patients was significantly higher (5 of 56) than in younger (6 of 257) patients (p = 0.015). In three of the five patients who died, urgent surgery was performed for obstructive jaundice, reflecting the higher mortality experienced by jaundiced patients in the entire series (9.4%). Biliary cultures grew organisms in 25 of 27 elderly patients (93%). This is in contrast to findings of bactibilia in 62 of 118 patients (53%) under the age of 80 (p = 0.001). Similarly, preoperative blood cultures were positive more often in elderly (63%) than in younger patients (26%) (p = 0.007). Mean postoperative hospital recovery was longer in the elderly group (16.2 +/- 8.5 days) than in the younger group (12.2 +/- 9.3 days) (p = 0.002). In conclusion, elderly patients, particularly those with obstructive jaundice, are at higher risk for complicated biliary tract disease necessitating choledochotomy. They appear to be more susceptible to bactibilia and bacteremia, and require longer hospital recovery than younger patients. PMID- 2252123 TI - Increased septic complications with three-drug sequential immunosuppression for cadaver renal transplants. AB - In 152 renal transplant recipients, the results of immunosuppression with three drug sequential (Minnesota antilymphocyte globulin, prednisone, azathioprine, and cyclosporine) immunosuppression (n = 107) were compared with those of a two-drug sequential protocol (Minnesota antilymphocyte globulin, prednisone, and cyclosporine) that excluded azathioprine (n = 45). The study groups were comparable by age, sex, etiology of renal failure, incidence of diabetes, and degree of HLA matching. Patient survival at 1 year was not significantly different in the two groups (two drug, 93% versus three drug, 86%; p = 0.19). One year graft survival was superior in the two-drug group (two drug, 93% versus three drug, 75%; p = 0.02). Analysis of primary transplants only (n = 116) yielded the same results. During the first year, the serum creatinine level remained stable in both groups. As expected, the three-drug therapy group had significantly more bacterial and viral infections. For low-risk primary cadaveric renal transplants, two-drug sequential immunosuppression is superior. PMID- 2252124 TI - Characteristics of duodenal wall gastrinomas. AB - Fifteen patients with duodenal wall gastrinomas (DWGs) and the Zollinger-Ellison syndrome have been treated since 1960. In 6 of 11 patients, DWGs were recognized at operation and totally excised. In four patients, the tumor was subsequently found in the proximal duodenum of the surgical specimens. In 12 patients, DWGs were single and lymph node metastases were present in 8. In three patients, DWGs were multiple and lymph node metastases were present in two. All DWGs were submucosal and all were located in the first or second portions of the duodenum except one found in the fourth portion. Tumor size ranged from 1 to 15 mm, and nine were less than 5 mm. Of 12 patients with single DWGs, 9 have remained eugastrinemic after resection (mean follow-up: 5.5 years). None of the patients with multiple DWGs became eugastrinemic after surgery. DWGs are characteristically single, small or microscopic, submucosal, located in the proximal duodenum, rarely metastasize to the liver, and are usually curable by surgical resection. PMID- 2252125 TI - Glucagonoma syndrome is an underdiagnosed clinical entity. AB - Glucagonomas, considered among the rarest of the islet cell neoplasms, produce a well-defined clinical syndrome characterized by necrolytic migratory erythema, diabetes mellitus, glossitis, anemia, and weight loss. This report describes seven patients with glucagonoma treated at our institution. All seven had the characteristic dermatologic manifestations, present from 1 to 6 years prior to diagnosis. Five patients had extensive disease at the time of initial operation, three of whom underwent aggressive cytoreductive surgery, whereas the other two had biopsy only. The remaining two patients presented with a single nodule each, underwent distal pancreatectomy and splenectomy, and remain free of disease 2 and 6 years postoperatively. Earlier recognition of the distinctive physical findings peculiar to this syndrome should increase survival. Aggressive cytoreductive surgery results in prolonged remission. PMID- 2252126 TI - Continent ileocolonic urinary reservoirs for filling and lining the post exenteration pelvis. AB - Pelvic exenteration has a high complication rate due, in large part, to the extensive raw surfaces and dead space it creates. Numerous techniques have been used to control this space and line these surfaces, but none, to date, has proven to be a reliable solution. We investigated the use of continent ileocolonic urinary reservoirs as a new "flap" to fill and line the pelvis in 17 patients, and found that our historical complication rate of 44% for pelvic exenteration was reduced to 18%. These reservoirs appear to be an improved method of managing the post-exenteration pelvis. PMID- 2252127 TI - The asymptomatic patient with suspected myocardial contusion. AB - Diagnostic criteria and guidelines for hospital admission for suspected myocardial contusion (MCC) remain unclear. This study defines and examines the clinical sequelae of patients admitted with a suspicion of MCC. Criteria for observation following isolated, minor blunt chest trauma are suggested. Hospital and trauma registry records of patients admitted over a 33-month period with suspected MCC were reviewed. Conventional evaluation criteria, cardiac-related complications, and associated injuries were analyzed for 524 patients. Twenty eight cardiac-related complications occurred in 27 of 524 patients (5%). These complications included 23 dysrhythmias, 3 infarctions, and 2 pericardial effusions. There were 23 patients with abnormal admission electrocardiograms and 4 with normal ones. Of the latter, one patient developed dysrhythmia 4 hours after admission, and three had other major multi-system injuries requiring admission to the intensive care unit. The overall incidence of cardiac-related complications in minimally injured patients was 0.1%. There were no complications in patients with isolated chest wall contusions, a normal admission electrocardiogram, and a normal rhythm at 4 hours. There was no significant association between creatine phosphokinase isoenzymes or echocardiogram and cardiac-related complications. The complete absence of significant cardiac sequelae in patients with isolated chest wall contusion, normal admission and 4 hour electrocardiograms, and no other associated major injuries suggests that these patients need not be admitted. PMID- 2252128 TI - Stunned myocardium during extracorporeal membrane oxygenation. AB - The "stunned myocardium" is a syndrome of reversible myocardial dysfunction that may be mediated by oxygen-derived free radicals. This phenomenon has been seen in some neonates undergoing extracorporeal membrane oxygenation. We performed echocardiograms and measured creatine phosphokinase isoenzymes and lipid peroxide levels in 16 neonates before, during, and after extracorporeal membrane oxygenation. Infants who developed stunned myocardia by echocardiography did so shortly after initiation of bypass and exhibited concurrent elevations of the MB fraction of creatine phosphokinase. Lipid peroxide levels did not simultaneously rise. These data suggest that oxygen-derived free radicals may not cause the stunned myocardium seen in neonates undergoing extracorporeal membrane oxygenation. PMID- 2252129 TI - Hypoxic events in the surgical intensive care unit. AB - An oxygen-monitoring protocol was established in the surgical intensive care unit (SICU) at the Denver General Hospital in July 1988. A 3-month surveillance audit ending March 1989 prospectively documented 100 consecutive hypoxic events in 51 of 241 (21%) SICU patients. These episodes occurred during mechanical ventilation in 46 patients, during spontaneous ventilation in 15 patients with artificial airways, and the remaining 39 occurred in nonintubated patients. Hypoxemia was recognized by pulse oximetry in 59, arterial blood gas analysis in 24, mixed venous oximetry in 15, and transcutaneous oxygen monitoring in 2. These events were due to problems with the ventilator or airway in 42, recent interventions in 21, new pulmonary process in 19, progression of underlying disease in 11, and unknown causes in 7. Two thirds resulted from mechanical problems amenable to simple intervention; there were two adverse outcomes. In conclusion, acute hypoxia is a frequent potentially morbid SICU event. Advances in continuous oxygen monitoring permit early identification and thereby may limit adverse outcomes, but should not prompt an expensive diagnostic work-up. PMID- 2252130 TI - Tertiary trauma care in a rural state. AB - Trauma patients in rural areas usually have no access to regional trauma systems or designated trauma centers. Efforts to provide quality trauma care in small hospitals may seriously overextend local capabilities. The urban trauma center retains an important role in trauma care even when the initial care must be provided at the local level. Twenty-five trauma patients were transferred to University Hospital between 1985 and 1988 after definitive care was initiated in community hospitals. During the same time period, a total of 147 trauma patients were transferred to the trauma service. No information was available on the total incidence of trauma. Medical records were reviewed to determine the reasons for transfer. Major reasons included the need for further complex surgery, better critical care support, and inadequate blood banks. Trauma centers serving rural areas provide a valuable resource well beyond the initial 24 hours. PMID- 2252131 TI - Improved trauma care in a rural hospital after establishing a level II trauma center. AB - A study of motor vehicle accident deaths occurring in Napa County, California, from 1979 through 1983 showed that there was a preventable death rate of 42% for deaths that were not related to central nervous system injuries. After developing a Level II trauma center at our hospital, the preventable death rate decreased to 14%. This was statistically significant (total chi-square, 0.01 less than p less than 0.025). There was a significant increase in the average Injury Severity Score (34 versus 45, p less than 0.005) as well as significant improvements in the surgeon's response time (32 minutes versus 11 minutes, p less than 0.005) and in the time from hospital arrival to the start of surgery (3.6 hours versus 1.9 hours, 0.01 less than p less than 0.025). We conclude that these changes are indicative of improved trauma care and reflect favorably upon the effectiveness of a rural trauma center that meets Level II trauma center guidelines established by the American College of Surgeons Committee on Trauma. PMID- 2252132 TI - Selective nonoperative management of patients referred with abnormal mammograms. AB - Screening mammography provides a means of detecting clinically occult breast carcinoma, but the question of whether all abnormal mammograms require biopsy remains unanswered. We retrospectively reviewed records of 214 women referred over an 8-year period for abnormal mammograms. They were selectively assigned to biopsy or mammographic follow-up based on specific mammographic criteria. Of 114 women initially observed mammographically, 2 were later found by biopsy to have carcinoma. Initial assignment to mammographic observation delayed the recommendation for biopsy 3 and 12 months, respectively, in these patients, but no effect on outcome was documented. Because they have benign lesions by clinical and mammographic criteria, 102 women (53%) have been spared biopsy; they continue to be monitored closely. We believe these data support the use of a selective approach to biopsy based on specific mammographic criteria. PMID- 2252133 TI - When is polypectomy sufficient treatment for colorectal cancer in a polyp? AB - Eighty-seven patients with a carcinoma in a polyp were reviewed over a 12-year period. Ten histologic criteria were analyzed for an association with the presence of residual carcinoma. Four factors were identified as having prognostic value: size greater than 1.5 cm, sessility, cancer of at least 50% of the adenoma volume, and invasive carcinoma. Polypectomy alone is adequate treatment unless the carcinoma invades deeper to the muscularis mucosa and is associated with one or more of these characteristics. PMID- 2252134 TI - Multimodal therapy in locally advanced breast carcinoma. AB - Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease. PMID- 2252135 TI - Outpatient percutaneous central venous access in cancer patients. AB - A 1-year experience of percutaneous subclavian catheterization in outpatients with cancer was reviewed to document reliability, safety, and cost. There were 763 catheter insertions attempted with prospective documentation of complications in 664 consecutive patients. Catheter insertion was successful in 722 attempts (95%). There were only 13 pneumothoraces (2%). Thirty catheters required repositioning (4%). The average catheter duration was 191 days (range: 0 to 892 days). Fifty-six catheters (8%) were removed because of suspected infection. Documented catheter sepsis occurred in 21 patients (3%); catheter site infection occurred in 8 patients (1%). Thus, only 0.22 infections per catheter year occurred during this 382 catheter-year experience. The estimated cost of catheter insertion was $562, which is one-third the estimated cost for tunneled catheters ($1,403) and for reservoir devices ($1,738). In our experience, percutaneous subclavian catheterization is a reliable, cost-effective method compared with tunneled or reservoir devices, with an equivalent incidence of catheter-related infections. The cornerstone of our success with this program is a staff dedicated to catheter care and intensive patient education. In centers where a large number of patients require central venous access, percutaneous catheterization should be the technique of choice. PMID- 2252136 TI - Kaposi's sarcoma of the rectum in patients with the acquired immunodeficiency syndrome. AB - We retrospectively reviewed eight patients with biopsy-proven anorectal Kaposi's sarcoma (KS) treated between 1984 and 1989 at San Francisco General Hospital. All patients were homosexual men with the acquired immunodeficiency syndrome (AIDS). The average age was 34 years. Three patients had primary rectal KS without metastases. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients with advanced AIDS received no specific treatment for anorectal KS. Follow-up ranged from 1 month to 5 years. Three of the untreated patients and the three patients treated with chemotherapy or radiotherapy were alive 1 month to 5 years after diagnosis. Aggressive surgical treatment of anorectal KS is not indicated. PMID- 2252137 TI - [Doppler study of the fetal and uteroplacental blood flows in IUGR]. AB - It was established during Doppler examination of the fetal and uteroplacental blood flow in intrauterine retardation in the growth of the fetus (IUGR) that the mean velocity of blood flow in the fetal aorta was 29.21 +/- 3.98 sm/s. It was statistically significantly lower than that in normal pregnancy. The mean velocity of the blood flow in the umbilical artery--30.90 +/- 5.82 cm/s and in the artery--54.22 +/- 15.48 cm/s were also lower than those in normal pregnancy, but the difference was not statistically significant. It is pointed out that the lack of terminal diastolic blood flow of the fetal aorta and the presence of double incisure of the artery arcuatus are pathological signs of Doppler wave. It is indicated the Doppler examination of the fetal and uteroplacental blood flow in IUGR is a new noninvasive method for early diagnosis of placental insufficiency. PMID- 2252138 TI - [The importance of the prophylactic use of antibiotics with women undergoing elective cesarean section]. AB - Postoperative infectious morbidity was described in two groups of low risk cesarean sections (CS). The frequency of postoperative infectious complications was 6.89% of women, who received penicillin for a period of 3 to 5 days, but 5.67% of women, who did not received antibiotics prophylactically. Data were presented, which showed also the economic insignificance of antibiotic prophylaxis (AP) in women with low risk CS. On the basis of the indicated data an inference was made that AP was of no clinical efficiency in women with low risk cesarean sections. The authors recommend restraint in AP of such women, in whom postoperative infectious inflammatory complications are anyway very rare. PMID- 2252140 TI - [The risk factors to the fetus and newborn infant with mothers under the age of 16]. AB - The study described risk factors for the fetus and newborn up to one year of age in 271 mothers under 15 years of age, using the alternative analysis. It was found that the body mass of the newborns of under age mothers was 328 g lower (Pt less than 0.0001) than the mean body mass of the whole population in the region, but the frequency of underweight newborns was twice as large. Perinatal infant mortality of the examined group did not differ from the mean mortality of the whole population in contrast to almost three-fold higher mortality in newborns up one year of age. Feeding and morbidity did not differ substantially from those of the remaining children in the region. Malformations were the most frequent cause for postnatal mortality. The authors conclude that inspite of accelerating processes the medico-social risk for still unborn infants of pregnant under age individuals remain rather high. PMID- 2252139 TI - [Delivery in prolonged pregnancy following preparation and induction with aprofen and prednisolone]. AB - In 51 chronological prolonged pregnancies at 42 weeks gestation the preparation and induction was made usage of the Soviet spasmolytic preparation Aprophen. Aprophen blocks also N-cholinergic receptors in sympathetic ganglia. The tocolytic action of sympathetic system on uterine musculature was removed as well as its tonic alpha-adrenergic effect on the cervix. Thirty pregnant women were included in a control comparative group, in whom induction and preparation of labour activity was achieved by usage of corticosteroids-Prednisolone. The medication in both groups continued till beginning of labour activity, but in failure after 96 h till oxytocin indication. In 77% of women, treated with Aprophen, labour activity occurred before 96 h (40 out of 51 women but 50% of women treated with Predinisolone (15 out of 30 women)/p less than 0.02/. In 31% of women, treated with Aprophen, labour activity was induced by oxytocin stimulation (14 out of 40 women, but in 76% of women, treated with Predinisolone (10 out of 15 women)/p less than 0.05/. The high percentage of children delivered with signs of postmaturity according to Clifford in pregnant women treated with corticosteroid--23.3% against 9.8% of women treated with Aprophen (p less than 0.01) show the connection between the usage of corticosteroids and the increase of the frequency of signs of postmaturity in newborns. PMID- 2252141 TI - [Pregnancy and myocardial infarct]. AB - The authors described the pregnancy and delivery of a woman with unstable angina pectoris (ECG data for ischemic disease of the heart). Delivery occurred through the vagina without complications for the mother and fetus. The literary references treat the question about course of pregnancy, way of delivery and analgesia in women with myocardial infarction during pregnancy. PMID- 2252142 TI - [Artificial abortion in Europe]. AB - The authors of the article review the state in various European nations and the possibilities for performance of induced interruption of pregnancy. In connection with this they describe the existing various forms of legislation. There are countries, in which induced abortions are absolutely band (Ireland). Legislation of socialistic countries is far more democratic in this respect. There are many factors, on which depend whether to legalize or not induced interruption of pregnancy. In Roman-catholic countries the religious motives are determinant, but in some other countries--the demographic policy of the government, ect. The practice however prove that induced abortions are widely distributes in Europe. The number of registered abortions is quite large in the socialistic countries. The data show that Bulgaria occupies one the first places (61.9% of women). Furthermore there are a series of problems in connection with the formation of high sexual culture of the population. Attention is paid to family planning all over the world. The question about contraception is an important and pressing problem. Good knowledge of current drugs and methods for prevention of unwanted pregnancy and their correct usage leads to a substantial reduction in the number of induced abortions and their unfavourable consequences. PMID- 2252143 TI - [The use of computers in obstetrics and gynecology]. AB - The authors describe usage of computers in obstetrics and gynecology presenting 4 basic activities: therapeutic-diagnostic, educational-teaching, scientific research, administrative-economic. The most characteristic usages of computers are given for each activity as well as the most interesting our and foreign programme products. PMID- 2252144 TI - [The determination of estrogen and progesterone receptors in the endometrium and myometrium]. PMID- 2252145 TI - [The effect of estradiol and reserpine on cortisol formation in sexually immature rats]. AB - The studies were carried out on immature female rats. The animals were divided into 4 groups: 1) treated with saline, 2) treated with reserpine, 3) treated with estradiol and 4) treated with estradiol and reserpine. Administration of drugs were made on 35, 36 and 37 day after delivery. There was statistically significant difference between the control group, treated with saline, and the group of rats, treated with estradiol. This is a new original fact for the presence of estrogen receptors in adrenal cells. Significant difference was found between the groups, treated with reserpine, and those, treated with saline and estradiol. The presented new data support the concept on the role of the adrenergic system in inhibiting hypothalamo-hypophysial-adrenal axis. PMID- 2252147 TI - [The characteristics of the x-ray image of the uterus bicornis]. AB - The results from a hysterographic study on women with bicornuate uterus are discussed. It is established that its frequency is 2.2% of 1623 performed hysterosalpingographies. A detailed analysis is made on the form and dimensions of the cornua [correction of corns], total isthmic part and cervical canal. Some metric parameters (height and width, sizes of the isthmus the an angle between the corns) are given with the purpose of greater precision of roentgenological interpretation. PMID- 2252146 TI - [The function of the hepatobiliary system in patients who have had inflammatory diseases of the uterus and adnexa]. AB - The function of the hepatobiliary system was studied on 60 women, undergone inflammatory diseases in the uterus and adnexa. The women of the basic group (n = 60) were divided into two subgroups in accordance with the state of genital organs. The first subgroup (n = 39) included women with residual manifestation of chronic salpingo-oophoritis. The second subgroup (n = 21) included women with tumours and tumour-like processes of genital organs, occurred on the back ground of a continuous inflammatory process. The control group included 10 healthy women. Dynamic scintigraphy of the liver and gallbladder utilizing Tc99 radionuclide with short duration of life, was used to determine the functional state of the liver and gallbladder together with biochemical parameters of blood. The obtained results showed that there were significant changes in hepatobiliary system of women with residual manifestations of chronic salpingo-oophoritis. In women with tumours and tumour-like processes of genitals, occurred on the background of continuous inflammatory process, there were significant disturbances in the engulfing-depurating function of the liver and gallbladder of hypokinetic type. PMID- 2252148 TI - [A report of 2 cases of the Herlyn-Werner-Wunderlich syndrome]. AB - Two cases are described, illustrating two varieties of comparatively little known, but not rarely encountered syndrome--the syndrome of Herlyn-Werner Wunderlich. The characteristic and the symptoms of the syndrome are presented and various concepts on therapeutic management are discussed. The question about future fertile capability of the patients is discussed as well. PMID- 2252149 TI - [Malignant neoplasms of the ovaries. The diagnostic and therapeutic results]. AB - The study included 291 women, who suffered from malignant ovarian tumours, hospitalized and treated in the gynecological clinic of the Higher Medical Institute in the town of Pleven during two period: of 1984-1988-168 patients and of 1980-1983-123 patients. A total 5-year survival was estimated for those women. The mean age of women was 55.08 +/- 15.79 years with a mean number of deliveries 1.82 +/- 0.78 and a number of abortions 2.03 +/- 0.75. The great relative part of epithelial tumours--91.66% was noted in the general structure similar to other distributions. The age groups of 40-49, 50-59 and 60-69 were mostly represented. An interesting case of a woman with an ovarian carcinoma at late stages with more than an 8-year survival was described. The total 5-year survival, estimated by the authors, for the period of 1980-1983, was 26.19%. The principles of combined treatment are discussed in accordance with the clinical stage, operative and histological results. The significance of some risk and prognostic factors are evaluated. PMID- 2252150 TI - [Gynecologic cytological cancer screening over an 11-year period]. AB - The results from compulsory gynecological screening programme for the period of 1977 to 1987 were described. A staining method with hemalaun--eosin was used. The results showed that 18,204 women were examined during prophylactic check up for a period of 11 years and their cytologic smears were diagnosed in accordance with Pap groups. 1.57% of women were under regular medical supervision till final recovery. Histological examination of biopsy or operative material was made in 54 women. The positive effect of screening on women for the investigated period was appreciated well It is indicated that the used routine and additional cytological methods are of good diagnostic reliability and high efficiency within the framework of the performed on cogynecological screening programme. PMID- 2252151 TI - [The incidence of idiopathic varicocele among andrological patients]. AB - The author carried out a study on 9753 andrologic patients, as idiopathic varicocele was established in 2102 (21.55%). In respect to age, the disease involved men most frequently between 21-30 years of age and this comprised 58.00% of the cases. In respect to family status he established that 77.00% of the cases were married without children, 6% of them were married with children and 17% of them were unmarried. In respect to profession the disease involved men with technical profession on the first place (34.00%), employees on the second place (14.70%) and chauffeurs on third place (12.00%). In conclusion the author indicates that the frequency of idiopathic varicocele is over 20% as 86% of men during fertile age are affected, but 77.00% of the examined cases suffer from disturbed fertility. PMID- 2252152 TI - [Migration of the placenta]. PMID- 2252153 TI - [Obstetrical management in prolonged pregnancy]. PMID- 2252154 TI - [A rare case of a giant ovarian leiomyosarcoma]. PMID- 2252155 TI - [Parasitic myoma. The difficulties in the differential diagnosis from an ovarian tumor]. PMID- 2252156 TI - [A clinical trial of the preparation palin in women with refractory colpitis]. AB - The authors carried out clinical trial of the preparation Palin (pipemidinic acid) on 43 women with persistent colpitis after preliminary testing. There was negative microbiological finding in 67% of women. The results of the authors differed from those of other authors, since Palin was used mainly in women with chronic colpitis resistant to routine treatment. Minimal side effects were found. Usage of Palin is recommended in women with colpitis, caused by: E. coli, Enterococcus, Klebsiella and mixed aerobic flora. PMID- 2252157 TI - [Delivery after cesarean section based on the data of the Obstetrical Gynecological Clinic of the Higher Medical Institute in Plovdiv for the period of 1984-1988]. AB - The authors studied the history of delivery of all women, who delivered for the period of 1984-1988. For this period 8981 deliveries took place, 849 of which (9.45%) by cesarean section. For the same period 193 women were admitted to the clinic after undergone cesarean section. 161 out of 193 women (83.4%) were delivered by repeated section. 113 women delivered by elective repeated section. Trial of labour was carried out on 80 women. 32 out of 80 women delivered vaginally. Trial of labour was unsuccessful in the remaining 48 women and delivery ended by cesarean section. The causes for failure in the trial of labour are discussed as well as the possible ways for increasing its efficiency. PMID- 2252158 TI - Detection of Chlorella-specific IgE in mould-sensitized children. AB - The content of IgE, specific to the unicellular green alga Chlorella sp., was analysed in sera from 46 atopic children sensitized to moulds, using radioallergosorbent test (RAST), immunoblotting and crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis (CIE/CRIE). Chlorella specific IgE was found in 23/46 sera by RAST, in 28/41 sera by immunoblotting and in 6/30 sera by CIE/CRIE. The Chlorella components most frequently binding IgE as analysed by gradient gel electrophoresis and immunoblotting were of molecular weights of approximately 13, 17, 19, 26 and 49 kD. Twenty-nine precipitating antigens, including seven IgE-binding precipitates were detected by CIE/CRIE. The study shows that low concentrations of specific IgE are formed to the green alga Chlorella in sera from atopic individuals sensitized to moulds. PMID- 2252159 TI - Antigen-induced dyspnea in Sprague Dawley rats. Effects of local treatment with anti-asthmatic drugs. AB - We wanted to study the effect of anti-asthma drugs on antigen-induced dyspnea in conscious Sprague Dawley (S.D.) rats. A line of dyspnea bred rats was produced, where all immunized animals respond with dyspnea when challenged with aerosolized ovalbumin (OA). The animals were immunized intraperitoneally (i.p.) with OA (10 micrograms) together with Al(OH)3 (100 mg) and challenged 2 to 3 weeks later with OA aerosol. We examined the effects of terbutaline (TERB), disodium cromoglycate (DSCG), atropine (ATRO), theophylline (THEO), a 5-HT receptor antagonist methysergide (METH), and two glucocorticosteroids (GCS) budesonide (BUD) and dexamethasone (DEX), on this response. The drugs were given locally either by intratracheal (i.t.) instillation or by aerosol. The rats were placed one by one in an air tight box and the breathing pattern was recorded. Parameters such as time of onset of dyspnea after end of challenge (elapsed time), duration and occurrence of dyspnea, were used to quantify the response. In the vehicle- treated group nearly all animals responded to OA with signs of dyspnea. TERB was the only drug effective when given as an aerosol, whereas when given i.t., also DEX and METH inhibited the dyspnea. Dyspnea is a serious response and can only be alleviated by the most effective anti-asthma drugs. PMID- 2252160 TI - Clinical significance of IgG subclass antibodies to wheat flour antigens in bakers. AB - We measured the IgG subclass antibody levels to wheat flour in 42 bakers and 20 controls with an enzyme immunoassay. The levels of total IgG, IgG1 IgG2 and IgG4 antibodies were significantly higher in the bakers than in the unexposed controls. The presence of anti-wheat flour IgG subclass antibodies in the bakers was correlated with various clinical variables including IgE levels, duration of asthmatic or rhinitis symptoms, skin prick test response, peripheral blood eosinophil levels, bronchial histamine reactivity and responses to nasal challenge with wheat flour. The IgG subclass antibody levels of the total cohort of bakers did not correlate with any of the measured clinical variables. However, among men specific IgG4 and IgG1 antibody levels correlated negatively with total IgE levels and duration of rhinitis, respectively. We conclude that IgG and IgG subclass levels to wheat flour in bakers reflect exposure, but that it is not related to any specific clinical situation. The exact pathogenic role of these antibodies in the development of occupational asthma and rhinitis is thus not clear. PMID- 2252161 TI - A double-blind study of hyposensitization with an alginate-conjugated extract of Dermatophagoides pteronyssinus (Conjuvac) in patients with perennial rhinitis. II. Immunological aspects. AB - In a 2-year double-blind placebo controlled study an immunological evaluation was carried out on 33 patients (15 males, 18 females, mean age 29.2 years) with mite induced perennial rhinitis who were submitted to specific immunotherapy (IT) with an alginate-conjugated extract of D. pteronyssinus. The behaviour of IgE, IgG, IgG1 and IgG4 antibodies specific to D. pteronyssinus and its major allergen Der p1 was characterized by assessment of their changes in serum, and changes in IgG in nasal secretions during the treatment. The placebo-treated patients did not show any significant variation in the levels of specific antibodies, while in the actively treated patients we found: a statistically significant decrease (P less than 0.005) of specific IgE, a statistically significant increase of specific IgG (P less than 0.005), IgG1 (P less than 0.005) and IgG4 (P less than 0.005) in serum and a statistically significant increase (P less than 0.001) of specific IgG in nasal secretions. The IgG response showed an early relative predominance of the IgG1 subclass and a late absolute predominance of IgG4 subclass, that confirmed the model of IgG4 restriction in prolonged allergen stimulation. No correlation was found between immunological and clinical data. PMID- 2252162 TI - Hay fever, eczema and urticaria in southwest Norway. Lifetime prevalences and association with sex, age, smoking habits, occupational airborne exposures and respiratory symptoms. AB - Information on hay fever, eczema, urticaria, respiratory symptoms, smoking habits and occupational dust or gas exposure was obtained by a self-administered questionnaire from a random sample of 4992 subjects of the general population aged 15-70 years of the Hordaland county, Norway. The response rate was 90% of the sample. The lifetime prevalences of hay fever, eczema and urticaria were 10%, 25% and 9% of the respondents, respectively. Eczema and urticaria were more often reported by women than by men. The lifetime prevalence of hay fever decreased substantially by age in both sexes. A history of hay fever was inversely related to cigarette smoking. The lifetime prevalences of eczema and urticaria were associated with occupational dust or gas exposure after adjusting for sex, age, smoking habits and area of residence. Adjusted odds ratios of respiratory symptoms in subjects with hay fever were almost 2.0 compared with those without. PMID- 2252163 TI - Lowered platelet glutathione peroxidase activity in patients with intrinsic asthma. AB - Platelet glutathione peroxidase (GSH-Px) activity and serum selenium (Se) levels were determined in 20 patients with intrinsic asthma. Nine of the patients had NSAID-intolerance. The mean value of GSH-Px activity in the patients was 47.0 +/- 7.1 U/10(11) platelets, which is significantly lower than that of 56.4 +/- 12 U/10(11) platelets in the controls (P less than 0.01). There was also a tendency towards lowered Se levels in the patients compared with controls. The results are discussed in view of the protective role of GSH-Px against oxidative stress and the tentative regulatory function of GSH-Px in arachidonic acid metabolism. PMID- 2252164 TI - Comparative safety and efficacy of short ragweed extracts differing in potency and composition in the treatment of fall hay fever. Use of allergenically bioequivalent doses by parallel line bioassay to evaluate comparative safety and efficacy. AB - One high potency (HP) and two low potency (LP) commercial whole short ragweed (WSR) extracts were assayed for relative potency (RP) by antigen E (AgE-Amb a 1), RAST inhibition, and parallel line bioassay (PLBA). The RP of the HP extract (300 micrograms AgE) was equal to the reference WSR, but the LP extracts were only approximately 0.01 of the RP of the reference. Each extract was administered to fall hay fever patients with skin sensitivity to WSR (less than or equal to 10( 3) micrograms/ml AgE for sum of erythema = 50 mm) to the maximum tolerated dose, or 0.5 cc of the concentrate, by either a 9- or 40-dose regimen. HP-treated patients had significantly lower symptom scores than untreated controls. No significant difference was noted in the total symptom scores between HP and LP extract-treated patients. Despite approximately 100-fold differences in the RP of HP versus LP extracts, both produced similar frequencies of severe systemic and severe late phase local reactions. Furthermore, when RP of HP and LP extracts were estimated by PLBA, both reached similar peak dosages, similar dosage for IgG WSR antibody response, and comparable IgG WSR antibody levels, indicating that the WSR dose estimates based on RP were bioequivalent. The 9-dose HP regimen produced fewer late phase local and systemic reactions per patient than the 40 dose HP regimen. Most patients experiencing severe systemic reactions were among those most skin sensitive to WSR. The number of systemic reactions per injection was significantly higher at higher WSR doses. One LP extract produced a high incidence of systemic reactions in the initial three injections. With respect to HP, its RP varied approximately 10-fold depending on the skin sensitivity of the patient to heat-stable ragweed allergens, demonstrating that it was compositionally different. However, when the dose of this extract was estimated by RP based on the skin sensitivity of each patient, the peak dose of the extract as well as the doses associated with late phase and systemic reactions were found to be similar to the HP doses. This indicated that immunizing dose estimates of compositionally different WSR extracts based on RP by PLBA were also bioequivalent. PMID- 2252165 TI - Infants and children with cow milk allergy/intolerance. Investigation of the uptake of cow milk protein and activation of the complement system. AB - Seventeen children with challenge-verified cow milk allergy/intolerance (CMAI), age 3-78 months, median 12 months, were re-challenged with cow milk in increasing doses. All subjects developed symptoms, such as bronchospasm, rhinitis, diarrhoea, erythema or eczema. Blood samples were taken before and up to 24 h after the start of the challenge. The cow milk protein beta-lactoglobulin (BLG) was determined in serum with ELISA (lower detection limit 0.3 micrograms/l). BLG was detectable in five children at low levels (below 2 micrograms/l). Analysis of the size distribution of the BLG by size exclusion chromatography indicated immunoreactive material as small aggregates. Plasma samples were analysed by electroimmunoassay for complement factor split product C3d, which was not demonstrable above background values in any of the cases. CMAI in infants and children may not be related to systemic activation of the complement system and may be elicited without considerable amounts of immunoreactive BLG in the circulation. PMID- 2252166 TI - Allergy to heroin. PMID- 2252167 TI - [Horst Stoeckel 60 years]. PMID- 2252168 TI - [An infusion model for intraoperative peridural anesthesia by catheter using mepivacaine]. AB - With the introduction of repetitive or continuous catheter techniques in regional anaesthesia, potential systemic intoxication hazards have increased. Especially high dose techniques such as peridural anaesthesia or plexus brachialis blockade consecutively generate high blood levels. In this study, blood levels collected from 20 patients (36 +/- 19 y, 173 +/- 9 cm, 73 +/- 15 kg) after lumbar epidural anaesthesia with mepivacaine led to the development of a linear open one compartment-model (VD,ss: 109 l, Cltot: 594 ml/min, t1/2abs: 13 min, t1/2 beta: 149 min). With that model, dosage strategies could be studied via computer simulation. A mepivacaine dosage regimen for lumbar epidural anaesthesia, consisting of 250 mg as an initial bolus dose and an infusion rate of 150 mg/h after 15 min, cumulated to maximum concentrations of 2.5-3.5 micrograms/ml after 150 min. Such an infusion regimen may lead to concentrations of more than 4 micrograms/ml if applied for longer than 4 h. The pharmacokinetic computer simulation proved to be precise and could be compared to the measured blood levels of mepivacaine. PMID- 2252169 TI - [The predictability of inspiratory and endexpiratory concentrations of isoflurane and enflurane using pharmacokinetic models and interindividual variability]. AB - The predictability of the inspiratory and endexpiratory concentrations of the volatile anaesthetics isoflurane and enflurane by pharmacokinetic models was investigated. 67 patients of ASA-classes 1-2 that underwent minor surgical procedures were studied. The pharmacokinetic model consisted of two parts, a model of the anaesthesia machine and a model of the patient. The mean values of the predicted/measured concentrations of isoflurane had an amount of 1.01 +/- 0.13 (inspiratory) and 0.97 +/- 0.13 (endexpiratory), the mean values of enflurane showed a value of 1.00 +/- 0.11 (inspiratory) and 0.97 +/- 0.13 (endexpiratory). The interindividual variances amounted to between 10% and 40% of the variance of all patients. This corresponded to a standard deviation of about 6% (inspiratory) while the endexpiratory concentrations showed a standard deviation about 8% for the average values of every patient. PMID- 2252170 TI - [The recovery period following total intravenous anesthesia using propofol and alfentanil versus inhalation anesthesia using nitrous oxide and enflurane at 1.3 MAC]. AB - Recovery of motor and mental functions were investigated in two groups with 20 young patients each. One group received total intravenous anaesthesia (TIVA) with propofol and alfentanil for urological surgery and the other group received nitrous oxide-oxygen anaesthesia in combination with 1.3 MAC of enflurane for lumbar nucleotomy. The following parameters were investigated before and up to 100 minutes after extubation: simple and discriminating motor activities, vigilance and short and long term memory. --Simple and in discriminating motor actions show a significantly faster recovery was seen in the TIVA group during the first 20 minutes after extubation compared to the enflurane-treated patients. Speech-related functions were particularly inhibited in the inhalational anaesthesia group. After 30 to 40 minutes the propofol-alfentanil group was able to meet all requirements while patients with inhalational anaesthesia needed 80 minutes to reach the same level. Recovery of short and long-term memory was also significantly shorter in the TIVA group. This clearly indicates a faster return of mental and motor functions following total intravenous anaesthesia with propofol and alfentanil. However the large dosages of alfentanil may be a problem with regard to post-anaesthetic respiratory depression. Further studies with larger numbers of patients will be necessary to evaluate the potential side effects of continuous propofol/alfentanil infusion. Presently, safety demands require, at least a sixty-minute post anaesthesia monitoring for patients receiving this new anaesthesia method. PMID- 2252171 TI - [Oxygen uptake and blood circulation parameters during anesthesia using EEG assisted determination of anesthetic dosages]. AB - Anaesthesia has significant effects on circulation and oxidative metabolism which are closely related to each other. Usually there is a marked reduction of oxygen uptake (VO2) and energy expenditure. A controversial discussion on the effects of the drugs administered and the degree of metabolic depression has continued in the literature fuelled by a lack of studies in patients under standardized conditions. 18 patients (ASA I-II) scheduled for major abdominal surgery were given closed-loop feedback control anaesthesia by quantitative EEG analysis. Group 1 received a total intravenous anaesthesia with methohexital and fentanyl whereas group 2 was given a combined anaesthesia with alfentanil and N2O. The aim of this comparative study was to evaluate the effects of different techniques for general anaesthesia on oxygen uptake and on the cardiovascular system. Preanaesthetic values of VO2 taken after flunitrazepam premedication were slightly below the predicted range determined by indirect calorimetry for basal metabolism. Steady-state general anaesthesia led to an approximately 30% reduction of VO2 for both groups. In contrast to oxygen uptake, blood pressure and especially heart rate were defined by the type of anaesthesia as in the methohexital fentanyl group higher values of both blood pressure and heart rate were observed. PMID- 2252172 TI - [The effect of positive end expiratory pressure on the blood flow velocity in the basal cerebral arteries during general anesthesia]. AB - The effects of incremental positive end-expiratory pressure (PEEP) on middle cerebral artery (MCA) blood flow velocity and pulsatility index were studied in 20 patients scheduled for minor elective surgery. Transcranial Doppler sonography (TCD) was used to measure systolic (Vsyst) and mean flow velocity (Vmean) and the pulsatility index (PI). Heart rate (HR), mean arterial blood pressure (MAP), end tidal CO2(PetCO2) and TCD parameters were recorded at control (PEEP = O) and following PEEP of 5 cm H2O, 10 cm H2O and 15 cm H2O for a period of 5 minutes for each PEEP level. Vsyst and Vmean were significantly reduced with each increment of PEEP. PI increased stepwise in response to each PEEP level. MAP decreased with PEEP 10 and 15 while HR and PetCO2 remained constant over time. These data suggest that PEEP-induced decreases in MCA blood flow velocity may represent decreases in CBF due to impairment of the intracranial venous flow if the diameter of the insonated vascular segment remains constant. PMID- 2252173 TI - [How safe is isovolemic hemodilution in elderly patients at risk? Clinical studies of geriatric heart surgery]. AB - The aim of this study was to evaluate isovolaemic haemodilution (IHD) as a method to reduce the use of homologous blood in high-risk geriatric patients undergoing cardiac surgery. Haemodynamics were continuously assessed in both the systemic and the pulmonary circulation, and, in addition, the EEG was continuously analysed by on-line power spectrum analysis. The mean blood use in this series could be reduced from 4.2 units to 1.12 units (67 patients). 73% of the patients needed intraoperatively no blood at all. The haemodynamic response to haemodilution in these patients consisted of an increase in stroke volume by 9%, and decreases in systemic vascular resistance and myocardial-O2 consumption (as reflected by the rate/pressure product RPP) by 9% and 10%, respectively. At the same time, O2 transport capacity increased by 8%. No signs of oxygen balance impairment were found in either ECG or EEG during haemodilution. It is concluded that moderate IHD can be safely performed in the geriatric cardiac patient and represents a useful method to reduce homologous blood use in these patients. PMID- 2252174 TI - [The efficiency of prehospital cardiopulmonary resuscitation. Which factors determine the outcome?]. AB - Survival rates following cardiopulmonary resuscitation differ widely with regard to the diverse rescue systems where the investigations were performed, and also with regard to the different patient populations. From 1981 to 1986, 1037 patients with out-of-hospital cardiac arrest were investigated in the city of Bonn. It was the purpose of this study to differentiate between various patient populations and to analyze factors which are responsible for CPR success. Survival rates following CPR could be increased from 8% in 1981 to 23% in 1984. Thereafter, a relatively stable survival rate of 20.1 +/- 1.7% with an initial CPR success rate of 62.5 +/- 8.1% was observed. Patients with ventricular fibrillation showed significantly higher survival rates (33.2 +/- 2.9%) when compared to asystolic victims (11.3 +/- 1.9%). The worst results were seen in these patients where CPR was initiated following trauma (8%) or in paediatric patients (8%). Factors which significantly determine survival following CPR are: initial ECG finding, therapeutic delay with regard to bystander-initiated basic life support, as well as advanced life support by emergency physicians. In addition, well standardized therapeutical strategies are of importance with early defibrillation, rapid endotracheal intubation and swift epinephrine application mostly by endobronchial administration. PMID- 2252175 TI - [Characteristics of cerebral blood flow and the electroencephalogram during experimental malignant hyperthermia]. AB - It is generally assumed that the brain is not primarily involved in the development of a malignant hyperthermia syndrome (MH). However, spontaneous brain electrical activity (EEG) has not been related temporally to the development of haemodynamic, respiratory and metabolic changes during a fulminant MH crisis. In the present study cerebral blood flow (CBF) and spontaneous electroencephalogram (EEG) were recorded in 8 pigs susceptible (MHS) for the development of malignant hyperthermia and 8 non-susceptible pigs (nMHS) after exposure to 1% halothane. Power densities in selected frequency bands were calculated from the EEG. Additionally, body temperature and haemodynamic and blood gas parameters were studied over a period of 60 min. MH was triggered in all MHS animals. Following exposure to halothane initial EEG changes were noted after 20 to 30 min. They consisted of a decrease in total power and a shift to lower frequencies (delta theta activity). At this time, CBF was significantly increased compared to control. In 4 animals an isoelectric EEG was noted at a PaO2 of 65-78 mmHg and PaCO2 of 52 to 64 mmHg. Characteristic changes for the development of an MH syndrome in haemodynamic and respiratory parameters as well as a rise in body temperature occurred after first EEG changes were seen. Our results do not support the hypothesis that early EEG changes during MH occur as a result of systemic hypotension, hypoxaemia, hypercapnia or cerebral ischaemia. Our data indicate that EEG monitoring in combination with monitoring of haemodynamic, respiratory and metabolic parameters may be of value for an early detection of an MH-crisis. PMID- 2252176 TI - [The effects of midazolam on the mechanical and electrical properties of the isolated ventricular myocardium]. AB - The direct effects of midazolam on isometric force of contraction (Fc) and on transmembrane action potential (AP) in electrically driven right ventricular papillary muscles were investigated. The results were compared with the effects of thiopental. Midazolam (0.01-200 mumol/l) had a concentration-dependent maximal negative inotropic effect of 94 +/- 4% compared with the pre-drug value on the papillary muscles of animals pretreated with reserpine (RES) [7.5 mg/kg b.wt. i.p., 16-18 h prior to the study]. The IC25 and IC50 values were 2.9 mumol/l (2.0 4.5; n = 9) and 12.4 mumol/l (6.5-30; n = 9) respectively. However, on the papillary muscles of untreated animals (nRES) midazolam developed a concentration dependent positive inotropic effect (maximal 20 +/- 7%). Midazolam at a clinically relevant concentration of 2.8 mumol/l (= 1 microgram/ml; equivalent with the maximum plasma level following a midazolam i.v. bolus injection of 0.15 mg/kg b. wt.) reduced Fc by 15 +/- 3% (p less than 0.05) compared with the pre drug value on the RES papillary muscles (n = 6) and increased Fc by 3 +/- 0.3% (p less than 0.05) on nRES animals. The resting membrane potential (RMP), the AP amplitude (APA) and the AP duration at 20% (APD20) and 90% (APD90) repolarisation showed no significant differences with midazolam (2.8 mumol/l; n = 5). Thiopental (0.01-200 mumol/l) produced a concentration-dependent maximal negative inotropic effect of 86 +/- 2% compared with the pre-drug value on the papillary muscles of nRES animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252177 TI - [Anesthesiologic implications in the Shy-Drager syndrome--a case report]. AB - Based on a case report with vaginal hysterectomy, the anaesthetic implications are discussed in a patient with Shy-Drager syndrome, which is a degenerative disease in middle-aged to elderly patients, resulting in autonomic dysfunction. The syndrome is reviewed and the anaesthetic management is described. Adequate cardiovascular monitoring and maintenance of haemodynamic stability are important. The response to sympathomimetic drugs is unpredictable and may be extreme due to denervation hypersensitivity. In the postoperative period, signs of postural hypotension may be severe and require training by elevation of the upper part of the body, fluid therapy, sympathomimetics and fludrocortisone. PMID- 2252178 TI - Interlocking connexion in anaesthetic systems. PMID- 2252179 TI - Fixation of the laryngeal mask airway. PMID- 2252181 TI - Preparation and use of propofol. PMID- 2252180 TI - Attachments to double lumen bronchial tubes. PMID- 2252182 TI - Ethics and research in anaesthesia. PMID- 2252183 TI - Recovery after day-case anaesthesia. A 24-hour comparison of recovery after thiopentone or propofol anaesthesia. AB - Sixty patients who presented for day-case dilatation and curettage were allocated randomly to receive either thiopentone or propofol for induction and maintenance of anaesthesia. One anaesthetist administered all the anaesthetics whilst all assessments were made by one other. The results indicate that early recovery of memory function, critical flicker fusion frequency and subjective feelings of tiredness, drowsiness and alertness were superior in the propofol group. There was a significant difference in subjective feelings of tiredness and drowsiness recorded by the two study groups at 24 hours. Memory function assessed by Wechsler logical memory function passages at 24 hours was impaired in the propofol group in comparison to a group of 'reference' subjects. PMID- 2252184 TI - Platelet function after intramuscular diclofenac. AB - A randomised double-blind controlled study was performed to examine the effect of diclofenac on skin bleeding time and in vitro whole blood platelet aggregation. Twenty thoracotomy patients were studied; 10 were given diclofenac 75 mg intramuscularly at induction of anaesthesia, and 10 formed a control group. Skin bleeding times and platelet aggregation tests were performed the day before and repeated one hour after induction of anaesthesia. Diclofenac prolonged skin bleeding time and reduced platelet aggregation. There were no significant changes in the control group. PMID- 2252185 TI - Posture and epidural catheter insertion. The relationship between skill, experience and maternal posture on the outcome of epidural catheter insertion. AB - This study was undertaken to investigate the outcome of epidural catheter insertion in the sitting or lateral position in mothers during labour. An initial prospective randomised study period (144 patients) suggested that the sitting position offered some superiority over the lateral in terms of technical ease of insertion. It was concluded, by minimising the subjective aspects in a follow-up, prospective nonrandomised study period (152 patients), that the determining factor lies in the skill and experience of the anaesthetist. There was no significant difference in complication rates or maternal discomfort between the two positions in either study period. PMID- 2252186 TI - The laryngeal mask airway in paediatric anaesthesia. AB - Forty-eight children, aged between 2 and 10 years, admitted as day cases for otological surgery were allocated at random into two groups. The first group was anaesthetised using a standard facemask, and the second with a laryngeal mask airway. The laryngeal airway produced a satisfactory airway in all children, and was inserted on the first attempt in 67% of patients. Hypoxia was significantly less frequent in the laryngeal airway group (p less than 0.05), and there were significantly fewer interruptions to surgery than in the facemask group (p less than 0.001). Patient safety, operating and anaesthetic conditions were all considered superior in the laryngeal airway group. PMID- 2252188 TI - Life-threatening complications during anaesthesia in a patient with a ventriculo atrial shunt and pulmonary hypertension. AB - A 6-year-old patient with hydrocephalus who underwent revision of a ventriculo atrial shunt is described. Anaesthesia was complicated by the occurrence of systemic hypertension and arterial hypoxaemia. The patient was subsequently found to have pulmonary hypertension secondary to recurrent pulmonary thromboembolism. The pathophysiological mechanisms for the patient's deterioration are discussed and the anaesthetic management of children with pulmonary hypertension is outlined. It is concluded that patients with a ventriculo-atrial shunt who present for surgery should be screened carefully for the presence of pulmonary hypertension. PMID- 2252187 TI - Flumazenil in ketamine and midazolam anaesthesia. AB - A double-blind, parallel group study using flumazenil and placebo was carried out to determine whether patients who received flumazenil would awake more quickly and whether this drug would reverse the protection conferred by midazolam on the psychic sequelae of ketamine. Fifty female patients were studied. The results showed that there was a significant reduction in awakening time (p = 0.02) and a very significant increase (p = 0.001) in the incidence of dreams in the flumazenil group. PMID- 2252189 TI - Nitrobenzene poisoning and spurious pulse oximetry. AB - The successful management of nitrobenzene poisoning in a 21-year-old patient is presented. We report our experience of ventilatory care with additional intravenous methylene blue and ascorbic acid therapy. Pulse oximeters available at present are not useful in patients treated with methylene blue and should be used cautiously in the presence of cyanosis of unknown aetiology. PMID- 2252190 TI - Dural puncture during attempted stellate ganglion block. AB - Dural puncture is rarely reported as a complication of stellate ganglion blockade. Breach of the dura occurred in the case described because of the anatomy of the cervical spine. PMID- 2252191 TI - The use of diazepam in chloroquine poisoning. AB - A 39-year-old patient was found to be unconscious after having taken 2.5 g of chloroquine. Treatment consisted mainly of gastric lavage and diazepam. Experimental and clinical evidence is presented to show that diazepam in varying doses significantly decreases the mortality rate. PMID- 2252192 TI - Caesarean section in a patient with haemoglobin SC disease and a phaeochromocytoma. AB - The anaesthetic management of a patient with haemoglobin SC disease for lower segment Caesarean section and excision of a phaeochromocytoma is described. The patient was given a general anaesthetic for the surgical procedure after exchange transfusion had achieved an haemoglobin A concentration of greater than 50%. A live infant was delivered and a suprarenal phaeochromocytoma was excised during a 6.5 hour procedure. The patient's postoperative recovery was uneventful. PMID- 2252193 TI - An evaluation of the Level 1 blood warmer series. AB - The Level 1 blood warmer series comprises three infusion sets and two blood warmers of different power outputs. All systems were found to be extremely efficient, with the larger 500 series capable of warming the equivalent of 80 units of blood an hour almost to body temperature. PMID- 2252194 TI - Embolism during caesarean section. AB - We investigated the occurrence of gas embolism during Caesarean section using a Doppler ultrasound probe and found that it occurs between uterine incision and delivery. Embolism is less common during general anaesthesia than has been reported during regional anaesthesia. Both ruptured membranes and a protracted uterine incision to delivery interval predispose to embolism. PMID- 2252195 TI - Anaesthesia in the field. Spontaneous ventilation--a new technique. AB - In recent years the British Army has used the Triservice Anaesthetic Apparatus in the field. Trichloroethylene is no longer manufactured in the United Kingdom and halothane is not recommended for closely repeated anaesthetics. A method based on existing equipment is described for patients breathing spontaneously. A background infusion of ketamine, midazolam and alfentanil supplements the inhalation of isoflurane in oxygen-enriched air. PMID- 2252196 TI - Postoperative sore throat: topical hydrocortisone. AB - Forty patients undergoing tracheal intubation and controlled ventilation of the lungs for elective surgical procedures were studied. They were allocated randomly into one of two groups. The tracheal tubes used for group A patients were lubricated before insertion with water-soluble 1% hydrocortisone cream. Those for group B patients were lubricated with KY jelly. The incidence of postoperative sore throat was found to be significantly greater in group A. Topical 1% hydrocortisone cream is therefore ineffective in the prevention of postoperative sore throat. PMID- 2252197 TI - Isolated lung transplantation for pulmonary fibrosis. AB - The peri-operative anaesthetic management of 11 patients with pulmonary fibrosis undergoing single-lung transplantation is presented. Intra-operative problems, the early postoperative phase of recovery and intensive care, and other incidents in which general anaesthesia was required for the management of complications, are featured. Results, both short- and long-term, are mentioned. Major intra operative events that cause concern appear to be related to the severity of the presenting illness and the development of respiratory failure. Others have reported the development of intra-operative cardiac failure. All cases were successfully managed operatively using conventional one-lung anaesthesia, although resort to partial cardiopulmonary bypass may have been indicated in some. The indications and attitudes to utilising cardiopulmonary bypass in the evolution of techniques for facilitating single-lung transplantation are reviewed. PMID- 2252198 TI - Was CEPOD right? AB - This retrospective study found that the long-term (greater than 6 months) postoperative survival in ASA 4E and 5E patients was 41% and 21% respectively, in 1986. This supports the Confidential Enquiry into Peri-operative Deaths' recommendation that life-saving surgery should not be withheld from patients who present in so serious a condition that they are unlikely to survive surgery. PMID- 2252199 TI - Two locum anaesthetists convicted of manslaughter. PMID- 2252200 TI - Anaesthetic research: new approaches need fresh attitudes. PMID- 2252201 TI - Unilateral spinal anaesthesia and prolonged femoral nerve block. PMID- 2252202 TI - Meningitis after spinal anaesthesia. PMID- 2252203 TI - Continuous epidural infusion. PMID- 2252204 TI - Race and Apgar scores. PMID- 2252205 TI - Occupational exposure to HIV and zidovudine chemoprophylaxis. PMID- 2252206 TI - Hyperkalaemia, cardiac arrest, suxamethonium and intensive care. PMID- 2252207 TI - Atracurium in whole body hyperthermia. PMID- 2252208 TI - HMEs and body temperature. PMID- 2252209 TI - Oximetry in pulseless disease. PMID- 2252210 TI - Noncardiogenic pulmonary oedema after attempted suicide by hanging. PMID- 2252211 TI - Pre-induction behaviour in children. PMID- 2252212 TI - Failed obstetric intubation. PMID- 2252213 TI - Laryngeal mask and magnetic resonance--a caution. PMID- 2252214 TI - Successful use of propofol in status epilepticus. PMID- 2252215 TI - Increased use of gum-elastic bougie in clinical practice. PMID- 2252216 TI - Unexpected airway obstruction. PMID- 2252217 TI - Central venous cannulation: two complications. PMID- 2252218 TI - Provoked gastro-oesophageal reflux? PMID- 2252219 TI - Malfunction of Servo ventilator in manual mode. PMID- 2252220 TI - Postnatal development of the interstitial tissue of the rat kidney. AB - To study the ontogenetic development of the interstitial tissue of the kidney, rats were investigated 1, 3, 7, 14, 21 and 28 days after birth. Kidneys perfusion fixed with glutaraldehyde were studied with light- and electron microscopy. Cryostate sections from kidneys immediately frozen in liquid nitrogen were studied with respect to the expression of MHC class II antigen using the monoclonal antibody OX6. The interstitial space of both the renal cortex and the outer and inner medulla was prominent during the first days postnatally. The relative interstitial volume of the cortex and outer part of the medulla then decreased in conjunction with the outgrowth and maturation of the superficial nephrons while the inner medullary interstitium remained wide. During the first postnatal days, the abundant interstitial cells of the cortex were connected via cytoplasmic processes to form a loose network which later became less well defined. The lipid-laden interstitial cells of the inner medulla showed essentially the same ultrastructure in the newborn as in the adult animal. Strong expression of class II antigen first appeared on epithelial cells of the thick ascending limb of Henle's loop about 7 days postnatally, and became weak at 28 days. From 21 days, a weak staining of the proximal tubules was also observed. While interstitial cells in the inner medulla were always negative, cortical and outer medullary interstitial cells became strongly positive for class II antigen from day 21 post partum. PMID- 2252221 TI - Segregation of fate during cleavage of frog (Xenopus laevis) blastomeres. AB - A detailed fate map of all the progeny derived from each of the blastomeres of the 4- and 8-cell stage South African clawed frog (Xenopus laevis) embryo is presented. Each "identified" blastomere that results from stereotypic cleavages has a characteristic set of progeny that distinguishes it from the other blastomeres of the embryo. The 4-cell dorsal (D) blastomere is the major progenitor of the stomodeum, cement gland, retina, notochord, head somite, pharynx and liver. The 4-cell ventral (V) blastomere is the major progenitor of the trunk and fin epidermis, ventral somite, nephrotome, lateral plate mesoderm and proctodeum. The other organs are derived from both blastomeres. At the next cell division, the animal hemisphere daughters of both blastomeres (D1 and V1, respectively) become the major progenitors for head ectodermal and mesodermal structures, and the vegetal hemisphere daughters become the major progenitors for trunk mesodermal (D2) or trunk endodermal (V2) structures. Semiquantitative lineage diagrams, using data from this and from previous studies demonstrate that as cleavage proceeds from the 2- to the 32-cell stage, the progenitors for particular organs or for specific regions of organs segregate into defined regions of the blastula. To determine whether this segregation is related to the position of the blastomere or to its geneological lineage, we compared the fates of radial 8-cell blastomeres to those of stereotypic 8-cell blastomeres. Radial blastomeres have fates nearly equivalent to the sum of the two 16-cell blastomeres that occupy the same position in the embryo, demonstrating that fate depends upon blastomere position rather than lineage. PMID- 2252223 TI - The effects of surgical section of the embryonic chick mandibular arch. AB - The embryonic chick mandibular arch was surgically sectioned in ovo on day 7 of incubation and the subsequent wound healing of the arch, together with the response of Meckel's cartilage to fracture, was examined. The repair process observed (in contrast to that in adults) was characterised by minimal haematoma formation or cell death and the absence of formation of either cellular blastema or fracture callus. re-epithelialisation was complete within 48 h with no scar tissue formed. Continuity of Meckel's cartilage, together with restoration of its histological appearance and that of the surrounding soft tissues, was re established within 24 h in 88% of cases. In the case of the cartilage this was due to fusion of the matrix followed apparently by chondrocytic and perichondrial proliferation. This differs from the repair of embryonic long bone cartilages. In 12% of cases, however, mal-union or non-union of the cartilage resulted in mandibular arch deviation. This observation suggests that mandibular arch growth and morphogenesis may parallel the development of Meckel's cartilage. Where cartilaginous non-union occurred, some irregularities in the pattern of the developing mandibular bones were evident, and it is argued that deformity in the cartilage may ultimately affect the length and shape of the adult mandible. PMID- 2252222 TI - The human brain at stages 21-23, with particular reference to the cerebral cortical plate and to the development of the cerebellum. AB - The development of the human brain during the eighth embryonic week was studied in serial sections of 22 embryos, and graphic reconstructions were prepared. The cortical plate appears in stage 21 in the area of the future insula and is an excellent feature for staging. The internal capsule contains neocortical fibres. Its three main outlets begin to be present in stage 22 and lead to epithalamus, to dorsal thalamus, and to mesencephalon. At this time a well developed lateral olfactory tract can be seen. The anterior commissure appears in stage 23. A clear developmental relationship between claustrum and olfactory area is described for the first time in human embryos. The optic tract reaches the ventral area of the lateral geniculate body. Scattered fibres of the lateral lemniscus reach at least as far as the caudal mesencephalon, in which superior and inferior colliculi can be distinguished at stage 23; two caudal Blindsacke containing ventricular recesses form in stage 23. The cerebellum is still present as a plate, but its internal bulge is considerably enlarged. It possesses radially- and tangentially arranged cells; the latter form the external germinal layer. The dentate nucleus, as well as the inferior and superior cerebellar peduncles and some of the cerebellar commissures, are present. Compared with the highly developed and probably already functional remainder of the hindbrain, the cerebellar plate shows far less differentiation. Two caudal migratory streams (marginal and submarginal) are present and represent the corpus pontobulbare. The decussation of the pyramids appears in stage 23. This article concludes the study of the developing human brain during the embryonic period, from stage 8 to stage 23. The series was based on 340 serially-sectioned embryos and graphic reconstructions from 89 brains. No comparable investigation of the fetal brain is available. PMID- 2252224 TI - Effect of surgeon's diagnosis on surgical wound infection rates. AB - To determine the impact of a surgeon's diagnosis of surgical wound infections on infection rates, during a 6-month period we prospectively examined patients undergoing surgical wound surveillance for any of four services (orthopedic surgery, general surgery, neurosurgery, or cardiovascular surgery). Criteria were judged as standardized if the infection control practitioner observed pus, redness, or drainage associated with positive culture or if a diagnosis of deep seated infection was made. Surgeon's diagnosis was judged as a nonstandardized criterion. Using the Centers for Disease Control's criteria, we identified 113 surgical wound infections in 3024 patients undergoing surgical procedures in the four services. Of these, 95 (84%) met objective criteria (pus observed in 53%; drainage, redness, and positive culture in 20%; and deep-seated infection in 11%). In 18 patients (16%), the nonstandardized criterion alone was used for diagnosis. There was wide variation in use of the nonstandardized criterion, ranging from 5% of orthopedic infections to 21% of cardiovascular surgery infections and 40% of neurosurgical infections. For individual surgeons with at least one wound infection, the range of surgeon's diagnosis was up to 67%. We conclude that a surgeon's diagnosis can have a major impact on surgical wound infection rates; this impact is not borne equally among surgical services or individual surgeons. PMID- 2252225 TI - Sterility of assembled heart-lung pump beyond 48 hours. PMID- 2252226 TI - Control of Clostridium difficile colitis outbreak by treating asymptomatic carriers with metronidazole. PMID- 2252227 TI - Ambulatory surgery postoperative wound surveillance. PMID- 2252228 TI - Limiting the use of urinary catheters to carefully selected patients. PMID- 2252229 TI - Nosocomial Escherichia coli O157:H7 diarrhea. PMID- 2252230 TI - Ageism in undergraduate psychology texts. AB - A sample of 139 texts written over the past 40 years was analyzed for evidence of ageism (i.e., lack of attention to the psychology of later life and stereotyping of older adults). More recent texts cover the topic more comprehensively than in the past, but this coverage is limited in depth. Although textbook authors appear to be trying to communicate a positive message about aging and older persons, their efforts are compromised by ambivalence in the form of contradictory statements about the nature of the aging process. There is an unfortunate condensation of sources in recent texts, which draw heavily from a small cluster of authorities. Implications of these findings for the larger textbook enterprise are discussed. PMID- 2252231 TI - Reducing adverse reaction to stress in the workplace. Psychology's expanding role. AB - This section draws attention to occupational stress and suggests ways in which psychologists can apply their knowledge of research methods and treatment to this issue. In this article, the past and present role of psychologists in occupational stress is examined and ways in which psychologists might play a more central role are proposed. Although industrial/organizational and health psychology are most obviously applicable to the study of workplace wellness, more focused attention and wider application of knowledge from other subspecialities are also examined. The need for increased attention to work and family; race, class, and gender; and training and public policy issues are also discussed. PMID- 2252232 TI - Occupational stress. Spice of life or kiss of death? AB - Work-related psychosocial stressors originate in social structures and processes, affect the human organism through psychological processes, and influence health through four types of closely interrelated mechanisms--emotional, cognitive, behavioral, and physiological. The health outcome is modified by situational (e.g., social support) and individual factors (e.g., personality, coping repertoire). The work-environment-stress-health system is a dynamic one with many feedback loops. There is little but increasing direct evidence of a causal relationship between work-related psychosocial stressors and the incidence and prevalence of occupational morbidity and mortality. But, a substantial body of indirect evidence strongly suggests that such associations exist and emphasizes the need to better understand their role. Accordingly, research and health action should aim at being systems-oriented, interdisciplinary, intersectorial, health- (and not only disease-) oriented, and participative. PMID- 2252233 TI - Prevention of work-related psychological disorders. A national strategy proposed by the National Institute for Occupational Safety and Health (NIOSH). AB - The National Institute for Occupational Safety and Health (NIOSH) recognizes psychological disorders as a leading occupational health problem. This document, developed by a NIOSH working group led by the present authors, represents a first attempt to fashion a comprehensive national strategy to protect and promote the psychological health of workers. Roles are identified for industry, labor, government, and academia. Key initiatives include (a) steps to improve working conditions and employee mental health services and (b) increased research and surveillance to advance understanding of the problem. Because work-related psychological disorders appear to be a rapidly developing problem lacking complete definition in terms of scope and etiology, this strategy is not to be considered a final statement of NIOSH policy. PMID- 2252234 TI - Psychology doctoral training in work and health. AB - Psychology as a profession has an opportunity and obligation to advocate for and develop healthy work environments. This will require the design and conduct of doctoral-level training in occupational health psychology. A model for training might well be based on the assumptions that there is a viable role for occupational health psychologists trained at the doctoral level for both academic and applied work settings, and that doctoral training would be based on the integration of health psychology and public health. Issues remaining to be addressed in the development of doctoral training programs include appropriate predoctoral training, academic standards, the interdisciplinary nature of faculties, and appropriate settings for training. Future directions in establishing doctoral training in occupational health psychology will best be taken in dialogue with several other professions and institutions that share a common interest in reducing leading work-related diseases and injuries and promoting public health in the workplace. PMID- 2252235 TI - Stress and the American worker. AB - Stress and stress-related diseases are considered as they relate to American worker productivity and global competitiveness. Occupational trends, current and future federal government efforts to address stress in the workplace, as well as external factors that contribute to stress are discussed. PMID- 2252236 TI - Mental health and the workplace. An interchangeable partnership. AB - Mental health is an important component of occupational health. The National Institute for Occupational Safety and Health (NIOSH) recognizes psychological disorders as one of the 10 leading work-related diseases and injuries (Millar, 1984). Job-related stress is receiving an increasing amount of public attention, and several studies indicate that stress-related conditions are among the most important health problems of the 1990s for people at work and outside of work. PMID- 2252237 TI - The Seville Statement on Violence. PMID- 2252238 TI - The eosinophil and acute lung injury. PMID- 2252239 TI - When the alveolus is flooding, it's time to man the pumps. PMID- 2252240 TI - Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. AB - Within 15 min of endotracheal intubation, the resolution of pulmonary edema was studied over the next 12 h in 34 mechanically ventilated patients by (1) serial measurements of the alveolar-arterial oxygen difference, (2) the extent of edema on the initial and follow-up chest radiograph, and (3) by an initial and final measurement of total protein and albumin concentration in sequential samples of pulmonary edema fluid. Based on the oxygenation and chest radiographic data, 24 patients clinically improved and 10 patients did not improve. In the 10 patients who did not clinically improve (3, hydrostatic edema; 7, permeability edema), there was no change in the final edema fluid protein concentration (4.1 +/- 1.1 g/100 ml) compared with the initial edema fluid protein concentration (4.2 +/- 1.0 g/100 ml) (p = ns). However, in the 24 patients who clinically improved (15, hydrostatic edema; 9, permeability edema), there was an increase in every patient's final edema protein concentration (5.6 +/- 2.3 g/100 ml) compared with their initial edema protein concentration (3.8 +/- 1.2 g/100 ml) (p less than 0.01). In 13 of these 24 patients, the final edema fluid concentration (7.3 +/- 1.6 g/100 ml) exceeded the final plasma protein concentration (5.6 +/- 0.8 g/100 ml) by a mean value of 1.7 g/100 ml protein. The data provide the first evidence in humans to support the hypothesis that active ion transport across the alveolar epithelial barrier is the primary mechanism for clearance of edema fluid from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252241 TI - Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. AB - Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension. PMID- 2252242 TI - Endotoxin in vivo impairs endothelium-dependent relaxation of canine arteries in vitro. AB - We studied the effect of endotoxin administration in vivo on arterial smooth muscle responses in vitro, testing the hypotheses that endotoxin augments adrenergic vasoconstriction and impairs endothelium-dependent vascular relaxation. Ten mongrel dogs were anesthetized and mechanically ventilated. Five received a bolus infusion of Escherichia coli endotoxin (5 mg/kg), and the remainder received a sham infusion. After 4 to 5 h, the anesthetized dogs were rapidly exsanguinated, and femoral, renal, and superior mesenteric arteries were removed. Arterial rings were mounted on force transducers in organ baths; contraction to phenylephrine or potassium-substituted Krebs-Henseleit solution (KCl), and relaxation to nitroprusside or acetylcholine were studied. Smooth muscle contractions to phenylephrine or KCl were similar between sham and endotoxin for each agonist. Also, nitroprusside-elicited relaxation from half maximal phenylephrine-elicited contraction was similar. However, relaxation elicited by acetylcholine was markedly impaired in vessels from endotoxin-treated dogs. The negative log molar concentration of acetylcholine producing 50% relaxation for femoral arteries was 7.38 +/- 0.11 (endotoxin) versus 8.09 +/- 0.12 (control, p = 0.002), for renal arteries it was 6.71 +/- 0.33 (endotoxin) versus 7.81 +/- 0.18 (control, p = 0.019), and for mesenteric arteries it was 7.27 +/- 0.03 (endotoxin) versus 7.95 +/- 0.15 (control, p = 0.002). These results demonstrate that endotoxin treatment impairs endothelium-dependent relaxation of canine arteries in vitro. The data suggest that vascular changes in endotoxemia are accompanied by alteration in endothelial cell function, perhaps through altered endothelial production of vasodilatory mediators. PMID- 2252244 TI - Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. AB - We tested the hypothesis that surfactant replacement would be beneficial in the acid-aspiration model of acute lung injury. HCl (0.1 N, 2 ml/kg) was injected into the trachea of excised rabbit lungs (n = 8). Control lungs (n = 4) had no intervention. All were perfused with Tyrode's solution mixed 1:1 with autologous whole blood at 40 ml/min/kg for 30 min, and then degassed. A modified natural surfactant (Survanta, Ross Laboratories) was then injected into the trachea of four lungs injured with HCl (100 mg/kg at 25 mg/ml). Two quasi-static pressure volume curves were determined. The mean alveolar pressures at 50, 60, 70, 80, and 90% of TLC were greater in the HCl group than in the control group (p less than 0.05). However, no difference was observed between the control lungs and those that received HCl + Survanta. In 13 anesthetized, paralyzed, and ventilated rabbits, deflation pressure-volume curves were determined from TLC to FRC (measured by helium dilution). Then, 0.1 N HCl (3 ml/kg) was injected into the trachea and, in seven, Survanta was instilled 5 min later. The mean alveolar pressures at 60, 70, 80, and 90% TLC were higher at 15 and 60 min in the HCl group compared with their pre-HCl time point (p less than 0.05). In the HCl + Survanta group, no differences were seen at 15 min, and only slight increased were seen at 60 min. No effect of surfactant replacement on arterial blood gases was observed. HCl aspiration increased recoil in both excised and in vivo lungs, and surfactant replacement with Survanta returned recoil to normal. PMID- 2252243 TI - The effect of corticosteroid or methotrexate therapy on lung lymphocytes and macrophages in sarcoidosis. AB - Methotrexate appears to be an effective alternative to corticosteroid therapy for some patients with sarcoidosis. The mechanism of action of methotrexate as an immunosuppressive is unknown. Patients with symptomatic pulmonary sarcoidosis underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage. Patients were treated with 10 mg methotrexate or prednisone weekly for at least 6 months and repeat studies were performed. A comparison was made between those patients receiving methotrexate (12 patients) and those receiving prednisone (12 patients). For both groups, there was a significant improvement in the vital capacity with therapy (Prednisone: Pre = 2.5 +/- 0.14 L (Mean +/- SEM); Post = 3.1 +/- 0.18 L, p less than 0.01; Methotrexate: Pre = 2.4 +/- 0.14 L; Post = 2.8 +/- 0.18 L, p less than 0.01). In addition, the percentage of lymphocytes in the lavage fell significantly for both the prednisone (Pre: 30 +/- 3.5%; Post: 16 +/- 2.7%, p less than 0.001) and methotrexate (Pre: 37 +/- 3.4%; Post: 13 +/- 2.9%, p less than 0.001) groups. Alveolar macrophages from the symptomatic sarcoid patients were found to be spontaneously releasing hydrogen peroxide and tumor necrosis factor. After treatment with either prednisone or methotrexate, alveolar macrophages retrieved by lavage spontaneously released less of either macrophage product. We found that effective doses of methotrexate for sarcoidosis led to significant changes in lymphocyte and macrophages retrieved by lavage. PMID- 2252245 TI - Inspiratory flow dynamics during mechanical ventilation in patients with respiratory failure. AB - We studied the effect of inspiratory flow rate on respiratory resistance during mechanical ventilation in 15 patients with acute respiratory failure (ARF). Resistance was measured by both constant flow inflation and occlusion methods as inspiratory flow rates were increased from 0.66 to 2.0 L/s. Endotracheal tube resistance was subtracted from total resistance to obtain respiratory resistance. In contrast to the flow-dependent increase in endotracheal tube resistance, respiratory resistance decreased continuously as flow rate and airway pressure increased, except in four of six patients with asthma in whom respiratory resistance increased as flow increased. Mechanical airway dilatation, tissue resistance, stress relaxation, and time-constant inequalities may contribute to the decrease in respiratory resistance. In status asthmaticus, however, the effects of turbulence, noncompliant airways, and/or "reflex" bronchoconstriction may be sufficient to cause a flow-dependent increase in resistance. PMID- 2252246 TI - Nasal and oral flow-volume loops in normal subjects and patients with obstructive sleep apnea. AB - Because flow-volume loops (FVLs) are clinically useful in evaluating upper airway (UA) obstruction and the fact that patency of the nasopharyngeal ventilatory pathway is important to the prevention of obstructive sleep apnea (OSA), the present study examined the role of nasal compared with oral FVLs in evaluating patients with OSA. Fourteen obese male patients 56 +/- 3 yr of age with a mean apnea plus hypopnea index (AHI) of 51 +/- 9/h were studied along with 14 nonobese, healthy, age- and sex-matched control subjects whose mean AHI was 6 +/- 1/h. Nasal and oral FVLs obtained in the normal subjects indicated the nose behaved like a variable resistor, with flow limitation during inspiration but not during expiration. In the patient group, flow limitation was observed during expiration as well as inspiration indicating nondistensibility of the nasopharyngeal ventilatory pathway in the patients compared to the control subjects. A change in body position from upright to supine in the OSA group was associated with small reductions in expiratory but not inspiratory flow rates. The area under the nasal supine flow-volume loop (FVLANaSup) was found to be highly correlated with awake resting PaO2 (r = 0.80) and PaCO2 (r = -0.83) in the patient group. In addition, multiple linear regression analysis revealed that PaO2 and the area under the nasal FVLs independently contributed to the prediction of AHI with a multiple R of 0.89. These results suggest that limitations to ventilation via the nasopharynx may significantly influence both gas exchange and the frequency of sleep-disordered breathing in patients with OSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252247 TI - Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness. AB - Persons with chronic mountain sickness (CMS) hypoventilate and are more hypoxemic than normal individuals, but the cause of the hypoventilation is unclear. Studies of 14 patients with CMS and 11 healthy age-matched control subjects residing in Lhasa, Tibet, China (3,658 m) were conducted to test the hypothesis that hypoventilation, blunted hypoxic ventilatory responsiveness (HVR), and hypoxic ventilatory depression of CMS were due to increased endogenous opioid production. Patients with CMS compared with control subjects exhibited hypoventilation (end tidal carbon dioxide pressure [PETCO2] = 36.6 +/- 1.0 versus 31.5 +/- 0.5 mm Hg, p less than 0.05), lower tidal volume (VT = 0.54 +/- 0.02 versus 0.61 +/- 0.02 ml BTPS, p less than 0.05), blunted HVR (shape parameter A = 17 +/- 8 versus 114 +/- 22 mm Hg/L BTPS/min, p less than 0.05), and a depressant effect of ambient hypoxia on ventilation (delta PETCO2 with acute hyperoxia = -3.5 +/- 0.5 versus 1.0 +/- 0.6 mm Hg, p less than 0.05). Reduced forced expiratory volume in 1 s to vital capacity ratios (FEV1/VC) and a higher proportion of cigarette smokers in the group of patients with CMS compared with control subjects suggested that at least some patients with CMS had mild airway obstructive lung disease. Naloxone infusion (0.14 mg/kg) to six patients with CMS did not change resting VT, PETCO2, HVR, or SaO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252248 TI - Severe anemia is an important negative predictor for survival with disseminated Mycobacterium avium-intracellulare in acquired immunodeficiency syndrome. AB - Disseminated Mycobacterium avium-intracellulare (MAI) in patients with the acquired immunodeficiency syndrome (AIDS) is usually unresponsive to antimycobacterial therapy. We examined clinical and laboratory characteristics of MAI organisms and their relationship to the length of survival. We studied factors influencing survival and compared these in 76 patients with AIDS with and without MAI. Serum levels of p24 antigen and erythropoietin, and CD4-positive helper T-lymphocytes in blood were assessed in 36 additional patients with various clinical stages of HIV infection. In patients with MAI infection, survival was significantly related only to total lymphocyte count, hematocrit, platelet count, and sex. Of these, hematocrit and total lymphocyte count were the only linear predictors of survival. Anemia was significantly more profound in patients with AIDS and MAI than in the other patients. This anemia in patients with MAI could not be ascribed to increased peripheral destruction of red cells, deficient nutritional factors, or erythropoietin production, HIV viral or bacterial load, or a general effect on other blood elements such as neutrophils or platelets. The influence of MAI on survival in patients with AIDS did depend upon whether the MAI occurred as an index infection or was preceded by other opportunistic infections. Patients with other preceding opportunistic infection lived for a much shorter duration from the time of diagnosis of MAI. PMID- 2252249 TI - Risk factors for Staphylococcus aureus nosocomial pneumonia in critically ill patients. AB - Staphylococcus aureus nosocomial pneumonia has become an important infection not only because of an apparently increasing incidence but also because of its high mortality rate. A total of 50 episodes of nosocomial pneumonia in critically ill patients in which etiologic diagnosis was well established were prospectively followed in a medical-surgical intensive care unit (ICU). S. aureus was isolated in a total of 13 episodes. In the univariate analysis the variables significantly associated with S. aureus nosocomial pneumonia were below 25 yr of age, coma, nonuse of corticosteroids, and antecedent trauma. A step-forward logistic regression analysis defined only coma as significantly influencing the risk of developing S. aureus nosocomial pneumonia. We suggest that antimicrobial drugs active against S. aureus must be included in the initial empirical antimicrobial regimen for treating nosocomial pneumonia in patients with coma. The identification of factors influencing the etiology and the possibility of earlier effective antimicrobial treatment may represent a further step in the control of nosocomial pneumonia in critically ill patients by improving its prognosis. PMID- 2252250 TI - Radiologic detection of pleural thickening. AB - The purpose of this study was to investigate four aspects of the radiologic detection of pleural thickening: the specificity of chest X-rays read by B readers, the effects of threshold definitions of positivity, the extent of variability among different X-ray readers, and the effect of film quality. A series of 421 chest X-rays corresponding to consecutive autopsies was reviewed by six B readers working independently and using modified International Labour Organization forms. The prevalence of true pleural thickening was approximately 6%. Using a strict definition of positivity, the average specificity was 0.85. Specificity decreased when a more liberal definition was used. (The average sensitivity was 0.32, which appeared to increase with a more liberal definition of positivity; because of small numbers of true positives, the sensitivity estimates were unstable.) Kappa statistics for interreader agreement ranged from 0.06 to 0.40, suggesting considerable interreader variability. Decreasing film quality was associated with decreasing sensitivity, but specificity was not affected by film quality. Because the chest X-ray has suboptimal test characteristics in the diagnosis of pleural thickening and because there is considerable interreader variability, we conclude that caution is required in interpreting radiologic detection of pleural thickening using ILO procedures. PMID- 2252251 TI - Path analysis of familial resemblance of pulmonary function and cigarette smoking. AB - The techniques of path analysis were utilized to assess the relative importance of genetic factors, personal smoking behavior, and shared environment in the resemblance of pulmonary function among relatives using both cross-sectional and longitudinal data from nuclear families. Data on 1-s forced expiratory volume, FEV1 (adjusted for age, sex, race, height, and ascertainment group) and the number of cigarettes smoked per day were available on 978 individuals in 384 nuclear families residing in the Baltimore metropolitan area. All these individuals were seen twice between 1971 and 1981, with an average of 5 yr between visits. The direct effect of an individual's own smoking explained 10 and 3% of variation in adjusted FEV1 among parents and offspring, respectively. Shared environmental factors influencing personal smoking behavior accounted for 5% of the parent-offspring correlation in adjusted FEV1 and 3% of the sibling correlation in adjusted FEV1 in this sample. Undefined environmental factors that influenced an individual's smoking habits and could be shared among relatives were found to explain 19% of the familial correlations in smoking. Genetic heritability estimates ranged between 36 and 40%, with no evidence of intergenerational differences in the expression of apparent genetic control of pulmonary function. PMID- 2252252 TI - The South Karelia Air Pollution Study. The effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms. AB - The paper mills in South Karelia, the southeast part of Finland, are responsible for releasing a substantial amount of malodorous sulfur compounds such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and methyl sulfides [(CH3)2S and (CH3)2S2], into ambient air. In the most polluted residential area the annual mean concentrations of hydrogen sulfide and methyl mercaptan are estimated to be 8 and 2 to 5 micrograms/m3 and the highest daily average concentration 100 and 50 micrograms/m3. The annual mean and highest daily concentrations of sulfur dioxide (SO2) are very low. We studied the effects of malodorous sulfur compounds on eye, nasal and respiratory symptoms, and headache in adults. A cross-sectional self administered questionnaire was distributed in February 1987 and responded to by 488 adults living in a severely (n = 198), a moderately (n = 204), and a nonpolluted community (n = 86). This included questions about occurrence of the symptoms of interest during the previous 4 wk and 12 months and individual, behavioral, and other environmental determinants of the symptoms. The response rate was 83%. The odds ratios (OR) for symptoms experienced often or constantly in severely versus nonpolluted and moderately versus nonpolluted communities were estimated in logistic regression analysis controlling potential confounders. The odds ratios for eye (moderate exposure OR 11.70, Cl95% 2.33 to 58.65; severe exposure OR 11.78, Cl95% 2.35 to 59.09) and nasal symptoms (OR 2.01, Cl95% 0.97 to 4.15; OR 2.19, Cl95% 1.06 to 4.55) and cough (OR 1.89, Cl95% 0.61 to 5.86; OR 3.06, Cl95% 1.02 to 9.29) during the previous 12 months were increased, with a dose-response pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252253 TI - Genetics of asthma and hay fever in Australian twins. AB - The occurrence of self-reported asthma/wheezing and hay fever among 3,808 pairs of twins from the Australian National Health and Medical Research Council Twin Registry was examined for evidence of genetic transmission by path analytic methods. The cumulative prevalence of asthma or wheezing was 13.2% and of hay fever, 32%. There were significant correlations in liability to reported disease among twins, and these were higher in monozygotic twins (MZ) (r = 0.65) than in dizygotic twins (DZ) (r = 0.25), and in male MZ twins (r = 0.75) compared with female MZ twins (r = 0.60). Analysis under the assumptions of the classic twin model suggested that there were genetic factors common to asthma and hay fever, with a correlation in genetic liability to the traits of 0.52 for men and 0.65 for women. These genes acted substantially in a nonadditive fashion in men but not in women. As the genetic correlation was significantly less than unity, this implied additional genetic factors influencing either or both diseases individually. The estimated heritability of these diseases was 60 to 70% in this population. Environmental causes of both diseases also were correlated (r = 0.53 for men and 0.33 for women). Cigarette smoking was only weakly associated with wheezing. PMID- 2252254 TI - Prevalence of occupational asthma and immunologic sensitization to psyllium among health personnel in chronic care hospitals. AB - Psyllium is a high molecular weight laxative that can cause occupational asthma among health care workers who prepare this product for chronically ill patients. The prevalence of immunologic sensitization and occupational asthma to psyllium is unknown. We investigated the personnel of four chronic care hospitals, including two where four cases of occupational asthma had been confirmed the year preceding the trial. A questionnaire and skin prick tests with psyllium and various inhalants were administered to 193 of 248 (78%) of the workers who agreed to participate. Seventy-five subjects (39%) had a history of respiratory symptoms in normal life and/or respiratory symptoms and/or rhinoconjunctivitis after handling psyllium. Six (3%) showed skin reactivity to psyllium. Increased specific IgE antibodies were found in 20 of 162 of the sera that were tested (12%). In the second part of the study, a histamine inhalation challenge was performed on 70 of 75 (93%) of the subjects with a history suggestive of asthma and/or occupational asthma and/or skin reactivity to psyllium. Twenty (29%) had significant bronchial hyperresponsiveness. The six subjects with a history suggestive of occupational asthma (n = 3) and/or asthma (n = 6) and/or positive skin test results to psyllium (n = 6) had significant bronchial hyperresponsiveness and increased specific IgE levels. They all underwent specific inhalation challenges with psyllium in the laboratory. Four developed bronchospastic reactions (two immediate and two dual reactions). We conclude that by including the initial four cases reported in the year preceding the initiation of this trial, the prevalence of IgE sensitization to psyllium was between 5 (skin testing) and 12% (increased specific IgE levels).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252255 TI - Changes in airway reactivity with age in normal infants and young children. AB - We have previously demonstrated that normal healthy infants exhibit airway reactivity to inhaled methacholine. The purpose of this study was to evaluate the changes in airway reactivity with age in infants and young children. We tested 24 healthy term subjects 4 to 24 months of age (mean 13 months) with history negative for lower respiratory illnesses and wheezing. Airway function was assessed by maximal expiratory flow at FRC (VmaxFRC), generated by rapid chest compression. After baseline measurements, each subject inhaled increasing concentrations of methacholine (Mch), beginning with 0.075 mg/ml, until VmaxFRC decreased 30% or Mch = 2.5 mg/ml. Sensitivity to Mch was defined as the threshold concentration (TC) required to decrease VmaxFRC 2 SD from control, and the Mch required to decrease VmaxFRC 30% (PC-30). Airway reactivity was defined as the slope between TC and PC-30 (SPC-30). We found significant regressions for TC, PC 30, and log SPC-30 versus age. TC and PC-30 increased with increasing age (r = 0.51, p less than 0.02; r = 0.63, p less than 0.001, respectively), indicating decreasing sensitivity to Mch with increasing age. Log SPC-30 became less steep with increasing age (r = -0.59, p less than 0.01), reflecting decreasing reactivity to Mch with increasing age. Of these infants, 10 had their Mch challenge repeated a mean of 8 months (range 4 to 11.5) following their initial test, with no lower respiratory illnesses in the interim.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252256 TI - Methacholine responsiveness among working populations. Relationship to smoking and airway caliber. AB - It has been suggested that the development of bronchial hyperresponsiveness (BHR) in some smokers may be an intermediate event in the progression to chronic obstructive pulmonary disease in this group. If this is true, prevalence data on BHR in a general population should show an independent association between BHR and smoking status. To test this, we analyzed BHR to inhaled methacholine in 654 white men without known asthma, in relation to smoking, skin-test reactivity, type of work (office versus industrial), and indicators of baseline airway caliber (FEV1 % predicted and FEV1/FVC). BHR was measured in the traditional way (PC20) and as the slope of FEV1 versus the methacholine concentration (linear scale). A PC20 of less than 16 mg/ml was considered "responsive" for analyses of this outcome. We found that although a positive skin test, smoking, and being an industrial worker all appeared to be significant predictors of increased BHR (p less than 0.05), once FEV1 (% predicted) and FEV1/FVC% were taken into account, none of these variables alone remained significantly associated with BHR. The strongest predictors of BHR were prechallenge FEV1 and FEV1/FVC (both p less than 0.01). The combination of smoking, atopy, and work groups, which identified a small subgroup of atopic smokers who were office workers, also remained significantly associated with increased BHR. We also used a regression model that allowed for comparison of predictors for BHR between the most responsive subset of the population (n = 84) and the remainder of the study population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252257 TI - Bronchoconstriction induced by inhaled sodium metabisulfite in the guinea pig. Effect of capsaicin pretreatment and of neutral endopeptidase inhibition. AB - Sodium metabisulfite (MBS), a commonly used preservative, induces bronchoconstriction in asthmatics, probably through the release of sulfur dioxide (SO2). The mechanisms involved in MBS- and SO2-induced bronchoconstriction are not yet certain. We aerosolized MBS or acid control solution (pH, 2.7) to anesthetized, tracheostomized guinea pigs pretreated intravenously with propranolol (1 mg/kg). MBS was given at increasing doubling concentrations (0.01, 0.02, 0.04, and 0.08 M) every 5 min. Steep concentration-response curves were observed, and most animals responded at 0.02 or 0.04 M. Tachyphylaxis was seen at high concentrations and during a subsequent MBS challenge 15 min later. For pharmacologic studies, we stopped the challenge when lung resistance (RL) had increased by at least 350%; a second challenge was found to be reproducible. MBS response was measured as the concentration needed to increase RL by 350% (PC350). Atropine (1 mg/kg given intravenously) did not affect PC350 or the peak RL response. Inhibition of neutral endopeptidase by inhaled phosphoramidon (7.5 nmol) administered before the repeated challenge did not alter PC350 value to MBS or peak RL responses (phosphoramidon, 201 +/- 49% of first peak; vehicle, 164 +/- 35%). In addition, the increase in RL was not prolonged in the phosphoramidon treated group. Animals treated subcutaneously with capsaicin (50 mg/kg) 1 wk before the experiment, so as to deplete neuropeptides from airway sensory nerves, had PC350 values similar to those of the control animals. Our data demonstrate that inhaled MBS causes bronchoconstriction in guinea pigs by mechanisms that are due neither to a cholinergic reflex nor to the release of tachykinins from airway sensory nerves. PMID- 2252258 TI - Effects of aging on diaphragm contractile function in golden hamsters. AB - The present study investigated the effects of aging on the contractile properties of the adult diaphragm in 42 Golden Syrian hamsters. Experiments were performed on isolated diaphragm strips from three groups of animals 4.9 +/- 0.4 (SE), 12.8 +/- 0.2, and 18.8 +/- 0.3 months of age. Aging was associated with a decrease in the maximal isometric tension generated per unit cross-sectional area of muscle and slowing in the time-to-peak tension and rate of muscle relaxation. The velocity of muscle shortening at a given load was also significantly less in older than in younger animals, and the force-velocity curve became flatter with advancing age as reflected by increases in the Hill coefficient (a/P0). Changes in maximal active tension and maximal velocity of unloaded shortening with aging correlated weakly (r greater than 0.3; p less than 0.05) and were of similar magnitude (-17 to -21%), suggesting that aging affects these two indices of muscle function in similar fashion. Finally, the diaphragm fatigued more rapidly in older than in younger animals. We conclude that aging depresses the ability of the adult diaphragm to generate tension and to shorten and resist fatigue. PMID- 2252259 TI - Effect of cooling on the responsiveness of canine tracheal muscle. AB - Airway cooling causes bronchoconstriction in many persons who have asthma. To determine the direct effect of cooling on the response of tracheal muscle to parasympathetic and muscarinic stimuli in situ, the temperature of a segment of canine cervical trachea was adjusted to 37 degrees, 30 degrees, or 25 degrees C by superfusing temperature-controlled saline over its epithelial surface. The contractile response of the tracheal muscle to electrical stimulation of the vagus nerves and to intra-arterial acetylcholine was then determined. Cooling the segment to 25 degrees C decreased the contraction induced by parasympathetic stimulation. However, cooling did not alter the contraction induced by intra arterial acetylcholine. Parallel studies were conducted in vitro using nine excised tracheal muscle strips taken from the same section of trachea in three additional dogs. Cooling the tracheal muscle to 25 degrees C in vitro increased the maximal contraction induced by both electrical field stimulation and by acetylcholine. Thus, cooling in situ does not alter the response of tracheal muscle to muscarinic stimuli and inhibits the response to parasympathetic stimuli. These data indicate that augmentation of the tracheal muscle response elicited by cooling in vitro does not reflect the response in situ. They suggest that a direct effect of cooling on airway smooth muscle response to parasympathetic and muscarinic stimuli does not account for cooling-induced bronchoconstriction in vivo. PMID- 2252260 TI - Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. AB - We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1% predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p less than 0.05) and normal control subjects (p less than 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p less than 0.05). EG2-positive cells (an index of secretion of eosinophil cationic protein following activation) were found at both airway levels in the asthmatic group and at level I in the nonasthmatic atopic control group (p less than 0.05). When asthmatic subjects were compared with normal healthy subjects, there was a reduction in the number of neutrophil elastase-positive cells in the asthmatic subjects which, as a percentage of leukocytes, was significant (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252261 TI - Activated eosinophils increase vascular permeability and resistance in isolated perfused rat lungs. AB - The effects of eosinophils activated with phorbol myristate acetate (PMA) on isolated perfused rat lungs were examined. Eosinophils were obtained from lungs of rats infected with Toxocara canis by bronchoalveolar lavage, incubated with PMA, and administered to an isolated perfused rat lung preparation. Vascular endothelial permeability was assessed by measuring the capillary filtration coefficient (Kf,c) in the perfused lungs. In lungs receiving either no eosinophils (control) or nonactivated eosinophils, there were no changes in pulmonary hemodynamics or Kf,c. However, in lungs receiving 2 x 10(6) eosinophils activated with PMA, there was a transient 4.8-fold increase in pulmonary vascular resistance that peaked at 30 min, primarily due to the constriction of small arteries and veins. After the initial pressor response, Kf,c was increased to 7.5 times control at 130 min and resulted in marked lung edema, increased wet-dry weight ratios, and edema on histologic examination. Pulmonary arterial pressure and Kf,c responses were dose related for eosinophil numbers between 1 x 10(6) and 4 x 10(6) cells. Peak airway pressure (Paw) during constant tidal volume ventilation also increased in lungs receiving activated eosinophils compared to the control and nonactivated eosinophil groups. These findings indicate that activated eosinophils are potent effector cells and can cause pulmonary vasoconstriction, bronchoconstriction, and vascular endothelial injury without widespread plugging of capillaries by aggregated eosinophils. PMID- 2252262 TI - Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. AB - To investigate the long-term effect of cigarette smoke on pulmonary structure and function, we exposed groups of guinea pigs to the smoke of 10 cigarettes each day, 5 days per week, for 1, 3, 6, and 12 months. We found that the guinea pigs developed progressive lung destruction (emphysema) and alterations in their pulmonary function tests similar to that seen in humans with cigarette smoke induced chronic obstructive lung disease. This method of smoke-induced lung destruction should provide a good model for the study of the early changes of emphysema. PMID- 2252263 TI - A rat model of prolonged pulmonary infection due to nontypable Haemophilus influenzae. AB - Pulmonary colonization and infection with nontypable (unencapsulated) Haemophilus influenzae (NTHI) occurs commonly in the setting of chronic lung diseases. Because the study of NTHI pulmonary infection in animal models has been limited by the rapid clearance of organisms, a model of persistent pulmonary infection was developed. Groups of rats were inoculated by transtracheal instillation of viable NTHI suspended in broth or semisolid agar. Some rats had received hexamethylphosphoramide (HMP) in drinking water before inoculation to cause respiratory epithelial mucosal damage. Groups of animals were sacrificed serially. Lungs were cultured quantitatively and their gross and microscopic anatomy examined. NTHI was recovered in small quantities from few broth inoculated rats after the first day of infection and in none after Day 7. In contrast, NTHI was recovered from the majority of animals and in greater amounts through 2 wk after agar-borne inoculation. HMP pretreatment further enhanced recovery through 4 wk after inoculation with an agar vehicle. The pulmonary inflammatory reaction was brief in broth-inoculated rats. The longer persistence of gross and histologic changes seen in agar-infected lungs paralleled the enhanced recovery of NTHI. Abscess formation occurred at 7 to 14 days in some agar-inoculated animals. Thus pulmonary inoculation of NTHI in a viscous vehicle resulted in perpetuation of infection and inflammatory response, and previous damage to respiratory mucosal epithelium induced by HMP further enhanced such infection. PMID- 2252264 TI - Inhalation injury to tracheal epithelium in an ovine model of cotton smoke exposure. Early phase (30 minutes). AB - The purpose of this study was to evaluate lung cell injury during the acute phase of smoke inhalation injury. A group of 10 sheep were anesthetized with halothane and pancuronium followed by endotracheal intubation. In the first experiment 5 sheep were given air (sham group) and 5 were insufflated with cooled cotton smoke with a modified bee smoker. In the second part of our study (Experiment 2) the animals were insufflated with the following number of smoke breaths: 1 x 12 (n = 3); 2 x 12 (n = 4); 3 x 12 (n = 4) 4 x 12 (n = 4); and sham control (n = 1). After 30 min the animals were killed with KCl and the trachea prepared for scanning, transmission electron, and light microscopy. Our initial observation with scanning electron microscopy revealed a large amount of mucus on the surface of the epithelia. Numerous ciliated cells had been sloughed from the epithelium and were observed on the surface of the remaining ciliated cells. The sloughed cells were intact, and the cilia remained on the apical cell surface. Light and transmission electron microscopy revealed that most goblet cells were in the process of extruding mucus. The cytoplasm of goblet and basal cells appeared normal. Ciliated cells had a slightly vesiculated cytoplasm, and many were in the process of being sloughed from the epithelial surface. In these cells desmosomal attachment had been separated. The light microscope evaluation of the tracheal epithelium showed there was no dose-dependent effect between the four treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252265 TI - Computed tomography of chronic diffuse infiltrative lung disease. Part 2. PMID- 2252266 TI - Bilateral intrapulmonary hematomas. AB - A 67-yr-old man, known to have chronic obstructive lung disease, developed bilateral localized pulmonary densities on chest radiographs after cardiopulmonary resuscitation. An autopsy disclosed bilateral intrapulmonary hematomas without communication with bronchi, pulmonary arteries, or pleural cavities. We suggest blunt pulmonary injury is the most probable cause of the hematomas and discuss its pathogenic mechanism. Intrapulmonary hematomas should be considered in the differential diagnosis of pulmonary densities developing after a vigorous resuscitation. PMID- 2252267 TI - Health effects of tremolite. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, June 1990. PMID- 2252268 TI - Artifacts in measuring airway areas by acoustic reflections. PMID- 2252269 TI - A cluster of silicosis in sandblasters. PMID- 2252270 TI - Effect of inhaled preservatives on asthmatic subjects: II. Benzalkonium chloride. PMID- 2252271 TI - Pyrazinamide in the chemoprophylaxis of tuberculosis. PMID- 2252272 TI - The ras oncogenes in human lung cancer. AB - The three well-characterized genes of the ras gene family H-ras, K-ras, and N ras, code for closely related 21-kD proteins that have a role in the transduction of growth signals. The ras proteins acquire transforming potential when a point mutation in the gene leads to replacement of an amino acid in one of the critical positions 12, 13, or 61. Overexpression of the normal protein, usually associated with gene amplification, can have similar effects. The detection of mutationally activated ras genes has been facilitated by the development of oligonucleotide hybridization assays that allow the identification of each possible mutation at the critical sites. Employment of the polymerase chain reaction has greatly increased the sensitivity of these assays. Studies of human lung cancer have shown that adenocarcinoma is the only subtype associated with ras mutations. These occur in about 30% of primary tumors. In almost all cases, the mutation is present in codon 12 of the K-ras gene. No mutations have been observed to date in tumors of nonsmokers, suggesting that the mutation may result from exposure to carcinogenic ingredients of tobacco smoke. Amplifications of ras genes were shown to be very uncommon in clinically early stages of lung cancer. Analysis of the clinical data of patients who were operated on for adenocarcinoma of the lung shows that K-ras mutations are not associated with particular histologic characteristics of the tumors or with specific presenting features. Patients with K-ras mutations, however, had significantly worse survival than did those without an activation. PMID- 2252273 TI - Progression through the cell cycle: an overview. AB - Tissues in adults can be maintained at constant mass or they can increase or decrease in size because of imbalances of synthetic and degradative processes acting at the cellular and molecular levels. Some size changes are caused by physiologic conditions to which the tissue must adjust. Alternatively, the balance may be distorted in favor of net tissue increase in pathologic situations such as cancer. Strict regulatory mechanisms are required to keep proliferation responsive to the organism's needs; these mechanisms may be defective in disease. Net tissue proliferation requires repeated rounds of cell duplication in excess of that necessary to counterbalance cell death. Duplication of a cell requires a net doubling of its every molecule and structure. The myriad of molecular events required for cell proliferation such as DNA duplication and its partitioning at mitosis are tightly regulated in normal cells. One may conceive of two classes of molecules: those required for "housekeeping," which constitute the cell's structural and functional machinery, and those such as growth factors, their receptors, and second messengers involved in signal transduction responsible for regulating the activities of the housekeeping molecules. These molecular events and the cascade of processes that control them can be organized within the sequence of the cell cycle. In this brief overview, we illustrate these issues with a few examples taken from very recent discoveries of novel proteins that appear to have major regulatory roles. Most of these results have been obtained with mammalian fibroblasts, but some have originated with discoveries made using two very different yeasts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252274 TI - Positive and negative regulation of proliferation and differentiation in tracheobronchial epithelial cells. AB - The lung (in particular the bronchial epithelium) is a major site for tumor formation in humans. Environmental factors in conjunction with genetic factors are important determinants in this disease. The acquisition of defects in the control of proliferation and differentiation appears to constitute crucial steps in the transition of a normal to a neoplastic cell. Several factors have been identified that control positively or negatively the proliferation and differentiation of tracheobronchial epithelial cells. These factors include EGF/TGF alpha, TGF beta, insulin/IGFI, KGF, certain cytokines, retinoids, and activators of protein kinase C. Studies with neoplastic cells have identified several protooncogenes and tumor suppressor genes whose gene products are involved in the regulation of cell growth of normal tracheobronchial epithelial cells, and when mutated, lost, or activated, bring about a neoplastic phenotype. Future studies on the precise function of these genes will help to elucidate the mechanisms by which proliferation and differentiation in normal tracheobronchial epithelial cells are regulated and help to understand the molecular changes involved in diseases such as cancer. PMID- 2252275 TI - Cell-to-cell communication and the control of growth. AB - Growth of transformed cells is inhibited by cell-to-cell communication with normal cells. This communication is regulated by certain oncogenes that alone or in cooperation can block the communication. PMID- 2252276 TI - Growth-related gene expression in type 2 alveolar epithelial cells. AB - Our laboratory is studying mechanisms of growth control in alveolar type 2 cells. This highly differentiated cell is induced to proliferate in lungs of animals of all ages during various forms of growth and during the repair process after lung injury. Using type 2 (T2) cells isolated from adult and neonatal rat lungs and an SV40-T transfected T2 cell line, we have shown tha growth-arrested T2 cells constitutively express genes associated with G1 and S phase of the cell cycle, yet they do not efficiently translate the proteins encoded by these genes. This block of growth-related gene expression is post-transcriptional and appears to involve mechanisms that control translation, perhaps at the level of initiation. Furthermore, growth-arrested T2 cells initiate DNA synthesis; however, the cells do not complete the cell cycle, suggesting that they are arrested in a late stage, perhaps the G1/S border. Differential screening of a cDNA library of growth-arrested T2 cells with DNA from growing and growth-arrested T2 cells has identified four families of genes preferentially expressed in the growth-arrested cells. These genes, which are in the process of being characterized, may be responsible for the unusual type of growth arrest demonstrated by T2 cells. PMID- 2252277 TI - Growth factor-regulated pathways in epithelial cell proliferation. AB - Investigations of the pathways regulating normal growth of epithelial cells have revealed the existence of two major growth-factor signaling cascades required for proliferation. One pathway is activated by IGF-1 or high insulin concentration. The other is triggered by EGF, TGF alpha, or members of the FGF family, including the recently discovered epithelial-cell-specific growth factor, designated keratinocyte growth factor (KGF). Its expression pattern in vivo suggests that KGF plays an important normal physiologic role as a stromal effector of epithelial cell proliferation. Oncogenes, which represent constitutively activated forms of genes critically involved in growth-factor signaling pathways, specifically abrogate the requirement for mitogens of the EGF pathway. Examples of such genes include the erbB/EGF receptor and erbB-2, which encode structurally related receptor proteins and are often amplified and/or overexpressed in epithelial malignancies. Employing reduced stringency hybridization with v-erbB as a probe, we recently identified a third member of this receptor family, designated erbB-3. cDNA cloning revealed a predicted 148-kD transmembrane polypeptide with structural features similar to those of the EGF receptor. Normal erbB-3 expression in keratinocytes and glandular epithelium suggests its physiologic role in these cell types. Moreover, markedly elevated erbB-3 mRNA levels in certain mammary tumor cell lines suggest that increased erbB-3 expression may also play a role in some human epithelial malignancies. PMID- 2252278 TI - [Treatment of HIV infection in childhood]. PMID- 2252279 TI - [Birth weight of children born without congenital defects. I. Birthweight percentiles by gestational age]. AB - We studied the birthweight by gestational age and sex from a population of 14,097 liveborns without congenital defects who were monitored by the Spanish Collaborative Study of Congenital Malformations (ECEMC). We have calculated the curves of percentiles for gestational age in males and females. As our sample size is very large, and it includes births from almost the whole country, we think these curves are enoughly representative of the Spanish population, fitter than the Denver's (1) which are widely utilized. On the other hand, we stress our attention in making curves of birthweight for malformed and not malformed babies separately. PMID- 2252280 TI - [Birth weight of infants born without congenital defects. II. Effect of tobacco and parity of the mother on the wight of the newborn infant]. AB - We analyzed the effect that number of gestations, smoking and number of cigarettes per day during pregnancy have on the birthweight using a sample of 14,097 liveborns without birth defects identifiable within the first three days of life. To our purposes, we controlled the effect of gestational age, sex and maternal age through multiple regression analysis. From the results we concluded that the birthweight is increased 39.80 g per each pregnancy of mothers, showing a progressive but smoothed increase by a negative quadratic effect. Smoking in mothers decreases the weight of newborns and has no effect on the gestational age. The decrease of birthweight was stronger when we looked at the number of cigarettes per day, showing a diminishing trend when the number of cigarettes per day, showing a diminishing trend when the number of cigarettes is increased, but again smoothed by a positive quadratic effect. From the multiple regression analysis controlling some factors we got a formula that permitted to us to estimate the average in decreasing weight depending on the number of cigarettes that mother smokes during pregnancy. PMID- 2252281 TI - [Spontaneous resolution of biochemical iron deficiency, without manifest relation to nutrition and growth, in a randomly selected group among the healthy population]. AB - In order to prevent iron deficiency, especially in children, iron-enriched foods are recommended in developed countries. In a random sample of 300 children (aged 6 months-16 years). 14 children between 0.5 and 4 years were diagnosed as iron deficient but without anaemia. Subjects were considered to present with iron deficiency if they possessed two or more abnormal values of the following biochemical parameters: red cell volume, erythrocyte protoporphyrin concentration, transferrin saturation capacity and serum ferritin. After one year, 12 of the 14 children on reassessment, were considered to be non-deficient in iron. During this period, we observed no statistical difference in dietary intake and growth rate between there iron deficient children and age and sex matched controls. This suggest that children presenting abnormal biochemical values, of iron status, could be observed in presence of normal dietary intake and growth rate, and does not necessary require rectification by dietary iron enrichment. PMID- 2252282 TI - [Vaccination coverage in a pediatric population attended by a primary health care center]. AB - It is hereby presented a quality control study of a systematic vaccination program developed in an urban primary care center. Target population were children between 0 and 8 years attended in the center. They were considered as having a correct vaccination coverage those cases in which it was possible to verify documented accomplishment of the local vaccination schedule. Out of the 538 children included in our study, 168 (31%) were founded not to have appropriate vaccination coverage evidenced in their clinical records, and their families were requested for an interview: 126 (75%) attended de appointment. In 93 of them it was founded a recording mistake, and 33 cases were verified as no correctly covered. Vaccination coverage rate was 86%, being inverse relationship between age and coverage rate. They are discussed corrective actions derived from the quality control. PMID- 2252283 TI - [Correlation between IGA from colostrum and serum and IGA is closer than between salivary IGA and total IGA]. AB - Colostrum, serum and saliva were simultaneously obtained from 50 normal mothers. 19-45 years old, 36-72 hours post-delivery. Total IgA level and class-IgA antibodies against 3 common food antigens (lactoglobulin, gliadin and ovalbumin) and 4 types of salmonella (typhi, paratyphi A, B and C) were determined in all samples. The 7 antibodies (Ab) were detected in colostrum, by ELISA, in a higher percentage of samples (88-62%), than in serum (82-34%) and saliva (77-27%). These percentages were higher for food-Ab than for anti-salmonella Ab. The total colostral IgA was close correlated with food-Ab in colostrum (p less than 0.001) and quite poorer with anti-salmonella Ab (p less than 0.05-p less than 0.01). A good correlation was generally also present between Ab from colostrum/serum, but was worse between both secretions (colostrum/saliva). The present results suggest that colostrum specific Ab levels can be predicted, depending on total IgA and the specific Ab from serum. PMID- 2252284 TI - [Socio-familial characteristics of children carriers of HIV antibodies. A disturbing factor of the clinical course of the disease to be recognized and controlled]. AB - A social study is made of 60 families with offspring presenting antibodies to HIV and monitored in our Service. Their data are compared with those obtained from an HIV antibody-negative control population randomly extracted from our Center. PMID- 2252285 TI - [Status asthmaticus; experience in a pediatric intensive care unit]. AB - Thirty children presenting status asthmaticus in fifty episodes were studied during a period of three and a half years. All of them showed acute respiratory failure secondary to asthma. The purpose was to evaluate treatment results and complications compared with a previous similar study conducted in our unit. We have noticed that there is a lower number of admissions for SA in our ICU and a different seasonal tendency. Precious treatment of asthmatic crisis selective inhaled beta 2 bronchodilators can prevent the ICU admission of an asthmatic patient. PMID- 2252286 TI - [Stress fractures in children: clinico-radiologic diagnosis]. AB - The authors present 4 children with stress bone fractures and review this entity. The most significant aspects in the mechanism of production of stress fractures are considered along with the appropriate steps for the diagnosis after careful history and physical examination, with special emphasis to the imaging diagnosis. PMID- 2252287 TI - [Xanthogranulomatous pyelonephritis: possibilities of diagnostic imaging]. AB - We report on two cases of xanthogranulomatous pyelonephritis (XGP) in children. In one patient preoperative diagnosis could be made on the basis of computerized tomography. Although XGP is a pathology diagnosis, new imagine techniques should allow its suspicion in a growing number of cases. This unusual disease should be suspected in from of a IVP showing non-functioning kidney specially when associated with urinary infection and/or lithiasis. Nephrectomy should be performed in all cases. PMID- 2252288 TI - [Kawasaki disease. Report of two cases]. AB - We present two reports of Kawasaki's disease. The first a five months old male, which was diagnosed through autopsy developed cardiovascular complications (myocarditis, coronary aneurysms, myocardial infarction) which led to death. The second one a two years and ten months old female, which was diagnosed at the fifth day of illness, was treated with aspirin at rate of 100 mg/kg/day and healed without consequences. It is interesting to emphasize the different development as a function of age, sex and precocity of diagnosis. PMID- 2252289 TI - [Homozygous familial hypercholesterolemia. Response to combined cholestyramine and lovastatin therapy]. AB - Homozygous familiar hypercholesterolemia (FH) is a serious inherited disease caused by a genetic defect in the cell surface receptor that controls the degradation of low density lipoprotein (LDL). These patients often have myocardial infarction in their teens or early adulthood and are usually unresponsive to drugs. Recently it has been reported promising results using combined drugs regimens in patients with residual receptor activity. We report a new additional patient with receptor-defective homozygous FH treated with a combination of lovastatin and cholestyramine. The cholesterol levels were reduced in a 67% and there were adverse events related to treatment during a 7 month period of follow-up. PMID- 2252290 TI - [Health care units for adolescents]. PMID- 2252291 TI - [Septic shock caused by Neisseria flavescens]. PMID- 2252292 TI - [King's syndrome. Malignant hyperthermia]. PMID- 2252293 TI - [Idiopathic hypereosinophilic syndrome in a 6 year old child]. PMID- 2252294 TI - [Intrahepatic biliary hypoplasia. Report of a case of an atypical syndrome]. PMID- 2252295 TI - [Idiopathic pericardial effusion in the neonatal period. Report of a case]. PMID- 2252296 TI - [Clinical and genetic heterogeneity in Robinow's syndrome. Report of a new case and review of the literature I]. PMID- 2252297 TI - [Metacarpophalangeal pattern as well as length and proportions of the bones of the extremities in an infant with Robinow's syndrome II]. PMID- 2252298 TI - [Hemorrhagic disease of the newborn and alpha-1-antitrypsin deficiency]. PMID- 2252299 TI - [Sirenomelia. Report of 3 cases]. PMID- 2252300 TI - [Surgical repair of a laryngo-tracheo-esophageal cleft]. PMID- 2252301 TI - [Transient hyperphosphatasemia in infancy. Report of a case]. PMID- 2252302 TI - [Do cases of asymptomatic leishmaniasis occur in Spain?]. PMID- 2252303 TI - History of serotonin and serotinin disorders. PMID- 2252304 TI - Serotonin receptor "families" in the central nervous system: an overview. PMID- 2252305 TI - The central 5-HT1A receptors: pharmacological, biochemical, functional, and regulatory properties. PMID- 2252306 TI - The 5-HT1B receptors. AB - The 5-HT1B receptors have been identified by radioligand binding techniques predominantly in the basal ganglia of the rat and mouse brain. A number of 5-HT receptor agonists have been shown to display high affinity but limited selectivity for the 5-HT1B recognition site. These include 5-CT, 5-HT, RU 24969, TFMPP, MCPP, and CGS 12066B. Antagonists at the 5-HT1B site include the drugs metitepin, metergoline, cyanopindolol, isamoltane, and propranolol but none of these drugs are selective for this receptor. Functional correlates of 5-HT1B receptor activation have been most closely defined in vitro. These include inhibition of transmitter release, inhibition of forskolin-stimulated adenylate cyclase and actions on the mouse urinary bladder strip and the rat vena cava. Many functional correlates of 5-HT1B receptor activation in vivo have been proposed, but convincing evidence from antagonist studies is generally lacking. The development of selective 5-HT1B receptor agonists and antagonists will be a key step in defining the physiological role of this receptor site in the brain and periphery of the mouse and rat although it must be realized that these compounds, if they are developed, are unlikely to have functional effects in man since the 5-HT1B recognition site is absent in the human CNS. Nevertheless many of these studies on the 5-HT1B receptor may aid the development of drugs acting at the 5-HT1D site since this receptor has been identified as being the equivalent of the 5-HT1B site in species other than the rat and mouse. PMID- 2252307 TI - The 5-HT1C receptor. PMID- 2252308 TI - Serotonin 5-HT1D receptors. AB - 5-HT receptors are subdivided into 3 families, 5-HT1, 5-HT2, and 5-HT3, of which subtypes have been described. The 5-HT receptor field has experienced over the last 10 years a revival due to the availability of new and more selective drugs and new techniques. This communication deals essentially with the biochemical approaches to characterize 5-HT1D receptors, and their comparison with 5-HT1B receptors. The methods used include radioligand binding, in vitro autoradiography, and second messenger studies. 5-HT1 receptor subtypes are labeled with [3H]5-HT and present a large heterogeneity: no less than 4 subtypes have been characterized: 5-HT1B and 5-HT1D are labeled respectively with [125I]cyanopindolol, and [3H]5-HT under appropriate conditions. Although some similarities are evident, the pharmacology of the two receptors is clearly different. Rat 5-HT1B receptors recognize with high affinity a number of beta adrenoceptor antagonists, such as SDZ 21-009, cyanopindolol, pindolol, propranolol and isamoltane. In contrast, calf, pig or human 5-HT1D receptors show significantly lower affinities for these drugs. 5-HT1D receptors show high to intermediate affinities to compounds such as PAPP, DP-5-CT, 8-OH-DPAT, yohimbine and rauwolscine, whereas 5-HT1B receptors have very low affinities for these compounds. The presence of 5-HT1B receptors has been documented convincingly only in rat, mouse and hamster. 5-HT1D receptors have been demonstrated in pigeon, guinea-pig, cat, dog, pig, calf, monkey, and man. The distribution of 5-HT1B and 5-HT1D receptors in all species examined so far, is very similar: high concentrations of sites are found in the nigro-striatal pathway, caudate-putamen, globus pallidus and especially substantia nigra. The subicullum shows also high densities of sites. Similar functional correlates have been proposed to 5-HT1B and 5-HT1D sites. Thus, 5-HT1D receptors are negatively coupled to adenylate cyclase in guinea-pig and calf substantia nigra, and 5-HT1B receptors are negatively coupled to adenylate cyclase in rat substantia nigra. Further, it is established that terminal 5-HT autoreceptors are of the 5-HT1B type in rat cortex, and of the 5-HT1D type in guinea-pig, pig, human and possibly rabbit cortex. In the rat saphenous vein, 5-HT1B receptors mediate inhibition of noradrenaline release. Preliminary evidence suggests that the canine basilar artery and saphenous vein, described as models for "5-HT1-like" receptors, could contain 5-HT1D receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2252309 TI - 5-HT2 receptors, roles and regulation. AB - Stimulation of 5-HT2 receptors in mammals by agonists causes detrimental neurological, psychological, and circulatory effects. 5-HT2 antagonists block the elicited effects, but by themselves, they do not cause any apparent behavioral, neurological or subjective effects. However, 5-HT2 antagonists increase slow wave sleep and have a therapeutic action on impaired circulation, dysthymia, and negative symptoms in schizophrenia. Chronic treatment of rodents with various 5 HT2 antagonists was reported to cause an anomalous desensitization and 5-HT2 receptor down regulation. In this study we further investigated the 5-HT2 receptor regulation in vivo and in vitro by agonist and antagonist treatment. Treatment of rats with the 5-HT2 agonist, 1-(2,5-dimethoxy-4-methylphenyl)-2 aminopropane (DOM) (2.5 mg/kg s.c., every 8 h), rapidly caused desensitization of the head twitch response (-20% and -80% after 2 and 4 injections) and a decrease in the number of frontal cortical 5-HT2 receptors labeled with [3H]ketanserin ( 24% and -41%, 24 h after 2 and 4 injections). The receptor resynthesis/degradation revealed half-times of 5 days initially to 3 days in the later drug-free period. Administration of the antagonist ketanserin (2.5 mg/kg, s.c., every 8 h) 15 min before the agonist, antagonized the acute behavioral effect but did not prevent the 5-HT2 receptor down regulation after 4 treatments. In contrast, ketanserin by itself, given 4 times, caused a reduction in the Bmax value of [3H]ketanserin binding by 19% and given 10 times it caused a reduction in the Bmax-values by 28% and 31% of [3H]ketanserin and [3H]DOB binding in the frontal cortex. Hence 5-HT2 receptors labeled by an antagonist and an agonist ligand were similarly decreased. In vascular smooth muscle cells in culture kept for at least 24 h in a serotonin-free medium before treatment, the 5-HT2 receptor mediated 5-HT-induced inositol phosphate formation, was rapidly desensitized by agonist treatment: -20% after 15 min and -80% after 1 h incubation of the cells with 10(-5) M 5-HT or DOM. After 2 h and 24 h treatment resensitization occurred with half-times of 5 h and 12 h, respectively. Pretreatment of the cells for 15 min or 24 h with 10(-7) M of the antagonists setoperone or ketanserin, followed by extensive washing, caused a reduction in the 5-HT-induced inositol phosphate formation by about 50% with setoperone and by 30% with ketanserin. Effects of 15 min and 24 h drug pretreatment were similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2252310 TI - 5-HT3 receptors. PMID- 2252311 TI - Serotonin receptors and phosphatidylinositol turnover. PMID- 2252312 TI - Animal models of serotonin behavior. PMID- 2252314 TI - Neurophysiological and neurochemical studies of brain serotonergic neurons in behaving animals. PMID- 2252313 TI - Endocrinological responses to 5-HT. AB - There is increasing evidence that neuroendocrine and temperature responses in humans can be employed to study the functional sensitivity of different 5-HT receptor subtypes. The evidence suggests that the PRL response to LTP is mediated by 5-HT1 receptors, perhaps the 5-HT1A subtype, though further studies are needed to confirm this effect. It is uncertain whether the PRL responses to other 'presynaptic' challenges of 5-HT function, for example, fenfluramine, are mediated by the same post-synaptic 5-HT receptor subtype as that for LTP. Conversely it seems likely that agonists which stimulate 5-HT2/1C receptors increase both plasma PRL and ACTH in humans. There is also evidence that 5-HT1A receptors can increase ACTH secretion. This suggests that in humans as in animals both the 5-HT1A and 5HT2/1C receptors can facilitate ACTH release, though the significance of this dual control is not understood. It is also possible that both 5-HT1A and 5-HT2/1C receptors stimulate PRL release, but 5-HT1A receptors may have a more prominent role in GH secretion. In both human and animal studies 5-HT1A and 5-HT2 receptor agonists may produce opposite effects on body temperature. These recent developments in 5-HT neuroendocrinology have been of great interest, but much is still uncertain. Progress in this field will be considerably advanced by the availability of new selective 5-HT receptor ligands, particularly selective receptor antagonists. PMID- 2252315 TI - Imaging the serotonergic system by positron emission tomography. PMID- 2252316 TI - Peripheral indices of central serotonin function in humans. PMID- 2252317 TI - Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal. AB - The serotonergic system is an early forming component of the CNS circuitry, beginning its development on gestational days 11-12 in the rat. Owing to its early presence in the embryonic nervous system, 5-HT has been proposed to act as a developmental signal for receptive cells. In vivo and in vitro evidence that 5 HT can influence both biochemical and morphological differentiation of raphe neurons and receptive target cells suggests that this neurotransmitter may have an organizing function in the developing nervous system which involves effects on neurite outgrowth and other aspects of neuronal differentiation, including synaptogenesis. Such functions may be mediated by a variety of 5-HT receptors located on both neuronal and non-neuronal cells. The apparent function of 5-HT as a differentiation signal in the developing nervous system raises important issues regarding the use of psychoactive serotonergic drugs by pregnant women, since these drugs may act as neural teratogens in the unborn child. PMID- 2252318 TI - Role of high affinity serotonin receptors in neuronal growth. PMID- 2252319 TI - The hyperserotonemia of autism. AB - The planned and ongoing studies of platelet function and composition should allow us to better define the alteration which we presume to be present in platelets of autistic subjects. Although much of the research focuses on serotonergic aspects, the more general research should permit a better delineation of the extent of the alteration and will protect against a premature narrowing of the inquiry. The methodological development which has been a necessary aspect of the work should contribute to an improved understanding of platelet function and composition, as well as result in improved clinical tools for the assessment of platelet functioning in neuropsychiatric disorders and hematology. As an example, improvements in short-term in vitro storage conditions to stabilize aggregation and shape change responses over time were found to be necessary, and are probably critical to an optimal comparison of these phenomena across groups. The identification of the platelet alteration which is responsible for the hyperserotonemia of autism should prove useful in several ways. It would be expected that assessment of the altered function would provide a marker with less overlap with the normal population than the multidetermined measure of blood 5 HT. Determination of the specific protein(s) involved in the altered platelet should lead directly to gene probes and chromosomal location. These, in turn, should prove useful for neonatal screening, subtyping, and more powerful genetic and family studies. Work of this sort might also allow early intervention and improved treatment. Finally, characterization of the physiological alteration would provide a basis for focusing studies of brain neurochemistry and should, as well, suggest modes of neuropharmacological intervention. The confidence that one can have in the basic finding of hyperserotonemia in autism and the potential benefits to be derived from its explication make further research in this area of great interest. PMID- 2252320 TI - Distribution of serotonin receptors. PMID- 2252321 TI - Serotonergic control of cerebral activity and behavior: models of dementia. PMID- 2252322 TI - Aging and regenerative capacity of the rat serotonergic system. A morphological, neurochemical and behavioral analysis after transplantation of fetal raphe cells. AB - Morphological dissimilarities between the brains of young (3 months) and aged (28 months and older) rats were demonstrated using serotonin-immunocytochemistry. A degeneration of the serotonergic system, noted as a decreased innervation and the appearance of enlarged or swollen varicosities, was observed particularly in the frontoparietal cortex, and the neostriatum of the aged rat brain. No direct relationship between this aberrant morphology and decrease in density of serotonin-innervation was found as we demonstrated a decline in fiber density without the appearance of aberrant serotonergic fibers in the hippocampus. HPLC analysis revealed that serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in the frontoparietal cortex, hippocampus and raphe area were increased in the aged rat, while the 5-HT level in the caudate-putamen complex was not different from the young adult rat. The ratio 5-HIAA/5-HT, indicative of 5-HT turnover, appeared increased in the frontoparietal cortex, sensoric part, the caudate-putamen and the raphe area, while this ration in the frontoparietal cortex, motoric part and the hippocampus was not altered in the aged rat. Behavioral screening revealed a decrease spatial performance of aged males in a Morris Water-Maze task. To investigate whether the age of the host recipient was of influence on the regenerative capacity, a fetal raphe cell suspension of embryonic day E 15 was implanted in the caudate-putamen of young adult as well as aged rats. Neither differences in survival of the serotonergic cells nor in fiber outgrowth between both groups appeared five weeks after transplantation. Subsequently, transplantation of raphe cells in the hippocampus of young adult rats, after lesioning the hippocampal serotonergic innervation with 5,7-DHT, was performed to compare behavioral, morphological and neurochemical effects of the implants. It appeared that 11 months after transplantation the serotonergic innervation of the previously denervated hippocampus was greatly restored. There was a striking resemblance between the immunohistochemical and neurochemical data with respect to the increase in the amount of newly formed serotonergic fibers, the increase in uptake of [3H]-5-HT and in 5-HT and 5-HIAA levels. Also the behavior of lesioned and lesioned + transplanted males was rather similar to controls. In the behavioral tests we were mainly interested in hippocampal functioning, therefore orientation was of our prime interest. The other behavioral tests were only to confirm that the possible changes were linked to hypothalamic or extra-hypothalamic functions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2252323 TI - Serotonin regulation of circadian rhythmicity. PMID- 2252324 TI - Effects of steroid hormones on the serotonergic system. PMID- 2252325 TI - Serotonin receptor subtypes and sexual behavior. PMID- 2252326 TI - Serotonin and sleep-wakefulness. PMID- 2252327 TI - Serotonin and suicidal behavior. AB - Studies of the brain of suicide victims indicate there is a decrease in brain stem levels of 5-HT and/or 5-HIAA. There also appears to be a region-specific increase in 5-HT2 receptors, which are post synaptic and may therefore be increased in number secondary to decreased serotonin levels. Lack of information about how 5-HT2 and other serotonin receptor populations are regulated hamper our ability to explain the mechanisms underlying these findings. If the initial reports of a decrease in the number of imipramine binding sites prove to be correct then this finding would be further evidence for an effect involving the serotonin neurons, seen in this case at the level of the terminals. The relationship between suicide attempters and completers remains to be worked out. However, studies of suicide attempters, particularly those making more lethal attempts, appear to confirm the findings made in the brain of suicide completers. Neuroendocrine and CSF studies indicate the presence of serotonin subresponsivity and lower levels of CSF 5-HIAA. Thus, the overall direction of change is towards a weaker serotonin signal which rather than being due to a primary receptor defect (a possibility that cannot be ruled out but for which there is no current evidence), appears to be due to reduced levels of serotonin release. The causes of this effect represent a research challenge. It is clear that reduced levels of serotonin alone cannot explain the timing and type of suicidal behavior. Future studies must address the role of other neurotransmitters which may explain why some aggression is directed outward (towards other people) and in other cases the aggression is directed toward the self (suicidal behavior). Defining the role of serotonin and other involved transmitter systems is a necessary step before a comprehensive pharmacological treatment plan can be designed and tested. PMID- 2252328 TI - Role of serotonin in depression. PMID- 2252329 TI - Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology. AB - Classical nosology has been the major cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, one we have designated as "functional," seems possible, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. We have pursued this route for many years, and based on the resulting findings we formulated the following hypothesis. Signs of diminished dopamine, serotonine, and noradrenaline metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions; i.e., hypoactivity/inertia; increased aggression/anxiety and anhedonia, independent of the nosological framework in which these dysfunctions occur (van Praag et al. 1990). In this paper only the 5 HT data have been discussed. Implications of the functional approach for psychiatry are discussed, including a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-oriented and therefore inevitably geared towards utilizing drug combinations. This prospect is hailed as progress, both practically and scientifically. PMID- 2252330 TI - Serotonin and nociception. PMID- 2252331 TI - Serotonin and appetite. AB - Feeding or food withdrawal can affect the supply of tryptophan to the brain and hence (in some circumstances) 5-HT synthesis therein. Also fenfluramine which releases 5-HT to postsynaptic receptors suppresses appetite, and there are reports that tryptophan can have a similar effect. Furthermore, feeding is reported to release hypothalamic 5-HT. Therefore 5-HT could have a role in the normal termination of feeding and perhaps also in disorders of appetite. The recognition of various 5-HT receptor subtypes has stimulated research in this area. We have now investigated the involvement of the subtypes in the pharmacological control of feeding. Thus, 5-HT1A agonists (8-OHDPAT, buspirone, gepirone, etc.) stimulate intake in freely feeding rats, probably by activating autoreceptors on the cell bodies of 5-HT neurons so that 5-HT release at terminals is decreased. The hyperphagia is not explicable by increased activity or gnawing and is strikingly manifest against carbohydrate in carbohydrate vs. protein choice experiments. Feeding in previously food-deprived rats is decreased by the 5-HT agonists RU 24969, 1-(3-chlorophenyl) piperazine (mCPP) and 1-(3 trifluoromethyl) phenyl) piperazine (TFMPP). Effects of antagonists on these properties suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors only, while mCPP and TFMPP induce hypophagia at 5-HT1C sites, though this effect also requires 5-HT1B receptors for its expression. Responsible sites occur in the paraventricular nucleus of the hypothalamus as infusing either RU 24969 or TFMPP therein causes hypophagia. On systemic injection, the hypophagic drugs are particularly active in female rats, an effect of conceivable relevance to human anorexic illness. PMID- 2252332 TI - Serotonin-storing secretory vesicles. AB - Advances have been made in the characterization of 5-HT-storing organelles of neurectodermal cells. The parafollicular cell of the thyroid has been used as a model. This cell stores 5-HT, shares many properties with neurons, and can be induced to change its phenotype from endocrine to neuronal by exposure in vitro to NGF. The membranes of isolated parafollicular 5-HT storage vesicles appear to contain a chloride channel that is gated in response to stimulation of the cells by secretogogues. Opening of this channel permits the interior of the vesicle to acidify in response to the action of a H+ ATPase in the vesicular membrane. Development of a delta psi appears to limit acidification of the vesicular interior when the chloride conductance is low. Transmembrane transport of 3H-5-HT into parafollicular vesicle is inhibited by dissipating the delta pH across the granular membranes. The physiological significance of the ability of parafollicular vesicles to modify the internal pH of their 5-HT-storing organelles remains to be determined. Like the synaptic vesicles of central and peripheral serotonergic neurons parafollicular vesicles contain a specific 5-HT binding protein, SBP. 5-HT storage organelles and SBP have been found in medullary thyroid carcinoma (MTC) cells, a tumor line derived from parafollicular cells. The cell biology of SBP is now under study utilizing the MTC cells. PMID- 2252333 TI - Serotonin in human eating disorders. AB - The onset and progression of symptomatology in patients with anorexia nervosa and bulimia nervosa is complex. It is unlikely that dysregulation of a single neurotransmitter system would be sufficient to explain the pathophysiology of these disorders. The studies reviewed above provide preliminary evidence that decreased central serotonin function may contribute to the onset or persistence of binge eating episodes in patients with bulimia nervosa, including low weight anorexic patients with bulimic symptoms. Future clinical studies will benefit from the availability of selective serotonin receptor agonists and antagonists. Longitudinal studies through progressive phases of treatment and clinical remission will be important to clarify the contribution of dietary and body weight changes to results of neurotransmitter studies with eating disorder patients. PMID- 2252334 TI - Serotonin agents in anxiety. AB - The side effects and unwanted or unnecessary ancillary pharmacological properties of benzodiazepine anxiolytic drugs resulted in a continuing search for new agents with improved profiles of activity. Buspirone was the first novel drug to emerge from this search in almost thirty years. Investigations into its mechanism of action revealed a key role for serotonin in the pharmacotherapy of anxiety. A variety of serotonergic agents are now in preclinical and clinical development as anxiolytics, including 5-HT1A partial agonists, 5-HT2 antagonists, and 5-HT3 antagonists. In addition to the new drugs which will be developed as a consequence of these investigations, their clinical efficacy will prompt the development of new animal models of psychopathology, leading us ever closer to a full understanding of the neurobiological substrates of anxiety. In addition, deployment of these new agents in the armamentaria of the clinician and the basic scientist will lead to new insights into the treatment of other disorders and the biochemical mechanisms by which the effects of these drugs are obtained. PMID- 2252335 TI - Serotonin function and human anxiety disorders. PMID- 2252336 TI - Serotonin in obsessions, compulsions, and the control of aggressive impulses. PMID- 2252337 TI - Serotonin and migraine. AB - Migraine has long been considered as a "vascular headache" but clearly neurological mechanisms are involved. The pathophysiology appears to somehow involve serotonin, both peripherally and centrally, but its involvement may be just epiphenomenal. Adding to the enigma it is apparent that many of the presently available drugs for the treatment of migraine interact in one way or another with serotonin receptors. However, they tend to have a number of other unrelated actions and they are only of limited clinical value. Interestingly a promising new drug for the treatment of the acute attack, sumatriptan, has a very selective action as an agonist at a specific 5-HT1-like receptor sub-type, mediating vasoconstriction, which is localized on cranial blood vessels. Its action may, or may not, be independent of any involvement of serotonin in the genesis of migraine. Hopefully though, current attempts to determine sumatriptan's mechanism of action will shed further light on the pathology of migraine itself and the putative involvement of serotonin. PMID- 2252338 TI - Serotonin uptake and serotonin uptake inhibition. AB - Serotonin uptake carriers occur on serotonin neurons, on glial cells and on blood platelets. The uptake carrier on serotonin neurons inactivates serotonin that has been released into the synaptic cleft by transporting it back into the nerve terminal. The serotonin uptake carrier is the means by which blood platelets acquire serotonin, since they do not synthesize it. The function of the serotonin uptake carrier on glial cells is poorly understood. Selective inhibitors of serotonin uptake enhance neurotransmission via serotonergic neurons and have been useful pharmacologic tools for studying physiologic roles of serotonin neurons. Some serotonin uptake inhibitors are finding therapeutic uses in mental depression and other psychiatric disorders and in treating obesity and bulimia; other therapeutic applications continue to be evaluated. PMID- 2252339 TI - Morphology of central serotonin neurons. Brief review of quantified aspects of their distribution and ultrastructural relationships. PMID- 2252340 TI - Anatomy of the serotonergic system. PMID- 2252341 TI - [Harvesting multiple organs]. AB - The development of organ transplants is limited by the shortage of organs. The improvement of this situation depends on two factors: increased awareness by the general public that refraining from refusing the removal of organs from the body of a patient with brain death is the most modern form of solidarity; and increased awareness by the medical profession that removal of organs should be proposed for every patient with brain death and that adequate resuscitative techniques should be used to preserve the organs in these patients. When the decision to harvest organs is taken, the transplant specialists must decide whether an organ should be used or not. Advances have been made in preservation techniques but are still insufficient to allow a reduction in immunosuppression. The UW solution is a major advance for liver, kidney and pancreas transplants. During harvesting, the separation of the vascular pedicles requires a good knowledge of surgical anatomy. Furthermore, the needs of the other surgical groups should be taken into account and concessions made to allow the harvesting of the greatest possible number of organs and consequently the treatment of the largest number of patients awaiting organs. PMID- 2252342 TI - [Hautmann enterocystoplasty. Clinical and urodynamic study in 24 patients]. AB - Twenty-four patients with invasive bladder cancer underwent Hautmann enterocystoplasty. A study of the urinary continence revealed 100 per cent of good results during the day and 87.5 per cent of good results at night. Urodynamic investigation after 3 months revealed that only one patient presented with peristaltic waves and that the postmicturating residual urine volume was always less than 100 cc. There was no mortality in this series. The only uncertainty concerns the long-term outcome of these patients because of the risk of incomplete emptying and distension of the neobladder. PMID- 2252343 TI - [Female vesical instability: etiologic problems in 209 cases]. AB - Based on a series of 209 cases, the authors investigate the aetiological factors responsible for vesical instability in adult females. Fifty five p. cent of patients suffered from incontinence due to isolated urgency. These patients presented a history of neurological disturbances in 21 cases, total hysterectomy in 22 cases and surgery for incontinence in 54 cases. Sixty p. cent of cases presented with genital prolapse. There were 7 cases of urinary tract infection, 2 cases of renal stones and 2 bladder tumours. Urodynamic studies revealed 60 dysuric syndromes. The responsibility of urinary tract infection or genital prolapse in the development of vesical instability is questionable. Nevertheless, the frequency of genital prolapse in the present series argues in favour of deficiency of the perineal musculature which decreases the capacity for inhibition of the detrusor. Lastly, 40% of patients did not have any neurological causes or any vesical or adjacent pathology. These cases were described as idiopathic vesical instability for which the aetiopathogenesis remains unknown. PMID- 2252344 TI - [Electrocoagulation of the paraurethral glands (Reiser's operation) in women with urethro-cystalgia]. AB - One hundred nineteen cases of women with chronic urethrocystalgia were reviewed. The symptoms were dominated by urethral burning (83%) and pollakiuria (75%). Electrosection of the paraurethral glands according to Rieser's technique and resection of the urethral floor (100% of cases) were combined with hymeneoplasty in 9% of cases. The results concern 67 women with a mean follow-up of 6 years: cure: 36%; marked improvement: 34%; no change: 30%. The authors discuss the presence of paraurethral glands, their role in the urethrocystalgia syndrome and the place of Rieser's operation in their treatment. PMID- 2252345 TI - [Penile extensibility and erectile function. Preliminary results]. AB - Extensibility, one of the main biomechanical functions of the penis, has been studied in 422 subjects. Preliminary results showed that a) the flaccid penis was extensible; b) this extensibility was significantly correlated with both age and erectile function. Thus, the more penile extensibility decreased, the more erectile function became impaired. This loss of extensibility is caused by fibrosis of the penis, that mainly affects the corpus cavernosa and, by reducing distensibility, impairs the vascular events involved in erection. Evaluation of the extensibility of the flaccid penis is a new, simple, no-invasive and reproducible clinical test. It contributes to the etiologic diagnosis of impotence by detecting tissular anomalies of the erectile corpora. PMID- 2252346 TI - [Comparative study of deferential permeability in rats after microsurgical vasovasotomy using the Howard technique and vasovasotomy using microsurgical low energy CO2 laser]. AB - Microsurgery is the technique of choice for vasectomy reversal. This study was undertaken to compare the patency of the vas deferens in rats after vasovasostomy performed either according to the technique described by Howard or using low energy Co2 laser. Two groups of rats were operated on using a surgical microscope. Results were evaluated on the external appearance and histopathological studies of the anastomosis, as well as on patency as documented by a methylene blue test. Both techniques proved satisfactory, but results were clearly better with the laser method. These findings suggest that the laser technique should be preferred in human surgery. PMID- 2252347 TI - [Ablation of a retro-hepatic caval thrombus without a thoracic approach]. PMID- 2252348 TI - [Ureterocele complicated by lithiasis. A study of 4 cases]. AB - The authors report a series of 4 cases of ureterocele complicated by renal stones and treated in the Urology Department of the CHU of Sousse. The diagnosis was radiological and treatment was surgical, consisting of removal of the stones, excision of the ureterocele and ureteroneocystostomy. PMID- 2252349 TI - [Renal ectopic pheochromocytoma. A case report]. AB - The authors report the case of an ectopic pheochromocytoma without any clinical symptoms or laboratory signs which simulated a renal tumor during clinical and complementary investigations. The diagnosis was established by histology. The ectopic pheochromocytoma and the diagnostic problems of silent tumors are discussed. PMID- 2252350 TI - [Extra-adrenal pheochromocytoma. Report of two cases]. AB - Paraganglioma is rare neoplasm. The authors report two new cases. The first case was a 36 year-old woman who presented with post-micturitional episodes of hypertension. Radiologic and endoscopic investigations showed a left submucosal bladder neck tumor. A partial cystectomy was performed under neuroleptanalgesia. The postoperative course was uneventful is simple. The second case was a 61 year old woman who presented with a non secreting para-aortic paraganglioma. PMID- 2252351 TI - [Report of a case of malignant vesical pheochromocytoma. Diagnosis and therapy]. AB - Bladder pheochromocytoma is a rare, usually benign bladder tumor. An exceptionally malignant bladder pheochromocytoma is reported with more than 5 years follow-up. The study of our case, and the review of 15 other cases reported in the literature show that surgery is the only effective therapy. Partial cystectomy with regional lymphadenectomy, when feasible is the treatment of choice. Because metastatic occurrence may be late, we emphasize the importance of long term follow-up. PMID- 2252352 TI - [Nucleolar organizers: NOR. New prognostic factors in prostatic cancer. Preliminary results in 20 cases]. AB - The authors present a preliminary series if two groups of ten patients with advanced prostatic cancer with sufficient follow-up in whom the study of nucleolar organizers (NOR) was performed according to a new light microscopy argentaffin technique. This original technique was developed by D. Ploton at the CHU de Reims. The principles of the technique are presented. The interpretation of the results, very dispersed at the present time, leads the authors two us two new clinical and histological indicators estimating the degree of severity of the prostatic cancer: the index of clinical severity based on the quality of survival and its duration from time T0 and the multifactorial index of histological severity based on the WHO classification, Gleason grade and NOR. PMID- 2252353 TI - [Fibrous polyps of the urinary tract]. AB - The authors report five cases of fibrous polyps of the urinary tract, which is a rare disease, as Mazeman only reported 12 cases in his review in 1972. These cases confirm the polymorphic nature of the clinical presentation and the site of these tumours of mesodermal origin, essentially composed of richly vascular connective tissue covered with surface epithelium. Treatment is surgical and conservative. The authors performed two junctional resections, one ureterotomy, one ureteroscopic resection and one nephro-ureterectomy for a partially destroyed kidney. PMID- 2252354 TI - [Value of arterioscopy in the prevention of renal artery stenosis after transplantation]. AB - Renal artery stenosis is frequent after transplantation. The systematic pre operative search for arterial injuries by angioscopy allows a reduction in their incidence. The authors report a series of 60 transplantations with pre-operative angioscopy, which revealed benign injuries and two major injuries which were successfully treated surgically. This prevention allows a reduction in the incidence of stenosis from 12 to 6.6% according to a previous series of 210 transplantations without angioscopy. PMID- 2252355 TI - ["Wallstent" endoprosthesis in recurrent urethral stricture in men]. AB - Many patients are condemned to repeated urethral dilatations because of the poor efficacy of treatment for male urethral stricture. The authors have recently used a new urethral prosthesis: a metal-reinforced, meshed tube which opens in the urethra and maintains a it open allowing the urothelium to grow over. The prosthesis therefore becomes incorporated in the wall of the urethra. they have implanted this prosthesis in 21 patients with a mean age of 61 years, essentially in the bulbar urethra, for longstanding strictures measuring 5 to 35 mm and unresponsive to currently available treatments. The endoscopic insertion of the prosthesis is performed after dilatation. The mean follow-up is 9 months. The stricture was correctly treated in all patients (three patients required two sessions). The follow-up of these patients is short and the stability of these favourable results needs to be confirmed by a longer follow-up. PMID- 2252357 TI - [Ureteral endometriosis]. AB - Endometriosis, initially believed to be a gynecologic disease, occasionally involves the urinary bladder, and less frequently the ureters. Use of ureteral stents with an appropriate hormonal treatment can obviate the need for open surgery. PMID- 2252356 TI - [Non-seminomatous germ cell tumors of the testicles: therapeutic approach. Report of 31 cases]. PMID- 2252358 TI - [Results of treatment of superficial vesical tumors by transurethral resection alone and transurethral resection followed by an intravesical instillation of Calmette-Guerin bacillus]. AB - Superficial bladder tumors treated at the Henri Mondor Hospital from 1984 through 1988 were analyzed for recurrence and progression using the following prognostic parameters: stage (TNM classification, 1978), grade (G1, G2, G3), size, number of tumors, and tumor malignancy index as defined by the Besancon group. Forty-five patients were treated with transurethral resection alone (TUR group) whereas 30 had TUR followed by the prophylactic instillation of fresh Calmette-Guerin bacillus in the bladder (BCG group). In TUR patients, parameters predictive of progression included grade G3, multiple tumors, stage T1, recurrence within 6 months of TUR, and a tumor malignancy index above 455. None of these criteria were predictive of a response to BCG. Results obtained in the BCG group were comparable to those reported in the literature and confirmed the efficacy of BCG instillations to prevent recurrence and progression of superficial carcinomas of the bladder. PMID- 2252359 TI - Neurological complications of open heart surgery. PMID- 2252360 TI - Brain microemboli during cardiac surgery or aortography. AB - We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium-sized arterioles. Two other patients had a small number of the same microvascular changes following proximal aortography. Thirty-four patients and 6 dogs not undergoing cardiopulmonary bypass had none. (A 35th patient who had not undergone cardiopulmonary bypass or aortography showed a small number of dilatations; mediastinal air was a suggested source.) Some of the dilatations exhibited various forms of birefringence. Because most of the dilatations appear empty, we speculate that they are the sites of gas bubbles or fat emboli that have been removed by the solvents used in processing. These microvascular events, occurring only in conjunction with major arterial interventions, may be the anatomical correlate of the neurological deficits or moderate to severe intellectual dysfunction seen in at least 24% of patients after cardiac surgical procedures assisted by cardiopulmonary bypass. PMID- 2252361 TI - Methods for estimating the number of motor units in human muscles. AB - The number of motor units in the thenar muscle group was calculated by dividing the surface electromyogram and twitch force, in maximal stimulation of the median nerve, by estimates of the average electromyogram and twitch force from single units. The following three techniques were used to estimate the average electromyogram from single units: spike-triggered averaging from units recorded with a needle electrode, intramuscular microstimulation of motor nerve branches, and graded whole nerve stimulation at the wrist. The first two techniques also provided independent estimates of motor unit numbers based on the average force generated by single units. The five estimates (three based on the electromyogram and two on force) ranged from 116 to 170 motor units in the thenar group. Correcting for cancellation when unit responses sum to form the compound action potential or twitch increased the estimated number of units, which ranged from 130 to 179. The estimates were not statistically different from one another but were substantially lower than some previous electrophysiological estimates based on graded whole nerve stimulation. The recruitment pattern of single units during whole nerve stimulation was recorded and simulated mathematically. The most likely reason for the higher estimates in previous studies using graded whole nerve stimulation is shown to be alternation of motor units. Potential errors in all the techniques are discussed and compared. PMID- 2252362 TI - Motor unit numbers and contractile properties after spinal cord injury. AB - The number of motor units in the thenar muscle group was estimated in 11 patients with cervical spinal cord injuries. The surface electromyogram and twitch force, in response to maximal stimulation of the median nerve was divided by the average surface electromyogram and twitch of single units. The average single unit size was obtained by intramuscular microstimulation of motor nerve branches and by graded whole nerve stimulation, which provided three independent estimates, two based on the electromyogram and one based on force. The motor unit estimates from the patients covered a wide range. Some had essentially normal motor units both in numbers and contractile properties, while others had varying reductions in numbers of units. Those patients who showed a large reduction in motor unit numbers also had greatly enlarged units, which produced an average of up to sixfold the normal force. These enlarged units summed to produce maximal compound action potentials and twitches that were sometimes indistinguishable from normal. Magnetic resonance imaging scans of the cervical spine obtained from some patients provided independent evidence that patients with low motor unit counts had sustained direct injury to the anterior aspect of the spinal cord at the relevant segmental levels. Some patients showed a normal number of motor units long after the injury. No evidence of transneuronal degeneration could be demonstrated in the thenar group in these patients with the current techniques. PMID- 2252363 TI - Treatment of spasticity with botulinum toxin: a double-blind study. AB - We studied the effect of botulinum-A toxin on spasticity of the leg adductors in 9 patients who were either chair-bound or bed-bound with chronic stable multiple sclerosis. We injected botulinum toxin (400 mouse units) or placebo into the adductor muscles in a randomized, crossover, double-blind design. Two physicians, who were unaware of the treatment order, used an objective rating scale and independently assessed the patients; interobserver correlation was excellent (r = 0.93-0.81). We found that botulinum toxin produced a significant reduction in spasticity (p = 0.009) and a significant improvement in the ease of nursing care (p = 0.009). There were no adverse effects during this short-term trial. This is the first demonstration of the beneficial effect of botulinum toxin on focal spastic muscle contractions. PMID- 2252364 TI - Adult phosphorylase b kinase deficiency. AB - Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both. PMID- 2252365 TI - NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine depleted rats. AB - Systemically administered N-methyl-D-aspartate (NMDA) antagonists, MK-801 ((+)5 methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) and CPP (3 [(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate), potentiate the ability of L dopa (L-3,4-dihydroxyphenylalanine) to reverse akinesia and to alleviate muscular rigidity in monoamine-depleted rats. On the basis of these findings, it is proposed that NMDA antagonists may be beneficial as adjunctive treatment in the therapy of Parkinson's disease. CPP locally injected into the subthalamic nucleus, entopeduncular nucleus--the rat homologue of the internal pallidal segment--or substantia nigra pars reticulata of monoamine-depleted rats stimulates locomotor activity and alleviates rigidity, whereas local microinjection of CPP into the neostriatum is ineffective. These results make it unlikely that the neostriatum is the site of the antiparkinsonian action of NMDA antagonists in monoamine-depleted rats, whereas the subthalamic nucleus, internal pallidal segment, and substantia nigra pars reticulata appear to be important for the effects of NMDA antagonists. PMID- 2252366 TI - Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection. AB - We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy. PMID- 2252367 TI - Failure of nine-month phenobarbital administration to reverse amygdaloid-kindled seizure susceptibility in cats. AB - Upon completion of left amygdaloid kindling, 4 cats underwent long-term phenobarbital administration during the subsequent 5- to 9-month rest period. Plasma phenobarbital levels were maintained above 15 to 20 micrograms/ml and were restimulated following plasma phenobarbital washout. Three cats served as nonmedicated controls. All 7 cats were subjected to repeated 6-hour sleep monitoring for observation of interictal discharges, which were observed most often in the immediate postictal period. Their frequency decreased gradually throughout the experiment in both the medicated and control animals, but they never completely disappeared except from the contralateral amygdala in 1 medicated animal. Upon primary site restimulation, all of the medicated animals responded with a generalized convulsion once the afterdischarge was induced. When these animals underwent secondary-site amygdaloid kindling, 3 showed a positive transfer effect. The findings suggest that although phenobarbital is a potent anticonvulsant, it has little effect on the acquired seizure susceptibility of previously amygdaloid kindled cats. PMID- 2252368 TI - HTLV-I sequences are not detected in peripheral blood genomic DNA or in brain cDNA of multiple sclerosis patients. AB - Human T-cell lymphotropic virus (HTLV-I) was recently reported to be etiologically associated with multiple sclerosis (MS). Genomic DNA from peripheral blood lymphocytes and brain plaques of patients with MS was analyzed for the presence of sequences homologous to the HTLV-I pol gene using the polymerase chain reaction and dot blot techniques. Comparison of DNA amplification patterns between patients with MS, and with control subjects who have other autoimmune conditions, with those in healthy control subjects and with an HTLV-I-infected cell line indicates that HTLV-I pol sequence is not present in the peripheral blood of patients with MS, and that the virus is not active in MS brain plaques. PMID- 2252369 TI - Aggravation of myasthenia gravis by erythromycin. AB - Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction. PMID- 2252370 TI - Human immunodeficiency virus (HIV)-associated myopathy: immunocytochemical identification of an HIV antigen (gp 41) in muscle macrophages. AB - In a patient with acquired immunodeficiency disease syndrome (AIDS) and muscle weakness, a muscle biopsy specimen disclosed degeneration of muscle fibers, regeneration, and focal endomysial mononuclear inflammation. A conspicuous feature was the presence of perivascular macrophages within the endomysium that showed positive immunostaining for human immunodeficiency virus (HIV) (gp 41) antigen. HIV was not detected within myofibers. Our findings suggest an important role for the HIV-infected macrophage in the pathogenesis of this myopathy. PMID- 2252371 TI - Effect of digitalis on clinical symptoms and conduction variables in patients with multiple sclerosis. AB - Digitalis has been shown to reverse conduction block in demyelinated nerve fibers in experimental animals. In the search for a symptomatic treatment of multiple sclerosis, digoxin (0.02 mg per kilogram of body weight) was given intravenously to 7 patients with probable or clinically definite multiple sclerosis. All of these patients had temperature-dependent symptoms. In 3 patients, improvement of clinical deficits was observed concurrent with significant changes in evoked potential findings. Digitalis derivatives may be useful in ameliorating symptoms in selected patients with multiple sclerosis. PMID- 2252372 TI - Familial Creutzfeldt-Jakob disease without periodic EEG activity. AB - Four members of a kindred with Creutzfeldt-Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt-Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt Jakob disease, as it is in other slow transmissible encephalopathies. PMID- 2252373 TI - Intraaxial divisional oculomotor nerve paresis suggests intraaxial fascicular organization. PMID- 2252374 TI - Cerebral mycotic aneurysms are rare in infective endocarditis. PMID- 2252375 TI - Driving and Alzheimer's disease. PMID- 2252376 TI - Dopa-responsive parkinsonism with normal 6[18F]-fluorodopa positron emission tomography scans. PMID- 2252377 TI - Cabergoline: a long-acting dopamine agonist in Parkinson's disease. PMID- 2252378 TI - Extracellular amino acids in traumatic spinal cord injury. PMID- 2252379 TI - A life with biological products. PMID- 2252380 TI - Rickettsia species (as organisms). PMID- 2252381 TI - Antigenic variation of a relapsing fever Borrelia species. PMID- 2252382 TI - Molecular evolution and genetic engineering of protein domains involving aspartate transcarbamoylase. PMID- 2252383 TI - Molecular biology of cellulose degradation. PMID- 2252384 TI - Helicobacter (Campylobacter) pylori: a new twist to an old disease. PMID- 2252385 TI - Bioactive microbial products: focus upon mechanism of action. PMID- 2252386 TI - Coronavirus: organization, replication and expression of genome. PMID- 2252387 TI - General microbiology of recA: environmental and evolutionary significance. PMID- 2252388 TI - Functions of secondary metabolites. PMID- 2252389 TI - Sexual differentiation in malaria parasites. PMID- 2252390 TI - Variation and control of protein expression in Neisseria. PMID- 2252391 TI - The generation of genetic diversity in malaria parasites. AB - The genetic diversity among malaria parasites is considerable, and much scientific investigation has focused on the ramifications of this diversity. Here we have discussed types of genetic change that are related to phenotypic changes in the parasite. To date, these changes have not been observed to result from precise mechanisms like the antigenic diversity seen in trypanosomes. Rather, the parasite seems to depend upon less precise mechanisms for generating diversity in combination with the large number of organisms that accumulate during infection as a reservoir for selection. PMID- 2252392 TI - Molecular determinants of Leishmania virulence. PMID- 2252393 TI - The genetics of bacterial spore germination. PMID- 2252394 TI - The global epidemiology of HIV infection and AIDS. PMID- 2252395 TI - Determination of bacterial growth and activity at solid-liquid interfaces. PMID- 2252396 TI - Proteolytic processing of picornaviral polyprotein. PMID- 2252397 TI - Environmental application of nucleic acid hybridization. PMID- 2252398 TI - Regulation of the cell division cycle and differentiation in bacteria. PMID- 2252399 TI - Mycoplasmal genetics. PMID- 2252400 TI - The effect of massage on pain in cancer patients. AB - Evaluating the effectiveness of nursing interventions in decreasing pain is a top priority for clinical research. Unfortunately, most of the research on cancer pain relief has been limited to treatment studies involving the administration of analgesics. Research is needed to determine which nonanalgesic methods of pain control are effective and under what conditions. Consequently, an experimental study was designed to test the effectiveness of massage as an intervention for cancer pain. Twenty-eight patients were randomly assigned to a massage or control group. The patients in the massage group were given a 10 minute massage to the back; the patients in the control group were visited for 10 minutes. For males, there was a significant decrease in pain level immediately after the massage. For females, there was not a significant decrease in pain level immediately after the massage. There were no significant differences between pain 1 hour and 2 hours after the massage in comparison with the initial pain for males or females. Massage was shown to be an effective short-term nursing intervention for pain in males in this sample. PMID- 2252401 TI - Intravenous therapy management: who will develop insertion site symptoms? AB - In this multisite study, symptoms at the intravenous (IV) insertion site and the relationship of patient and clinical data to these symptoms are described. It was found that approximately 40% of the subjects experienced at least one site symptom. The most common was pain. Presence of symptoms was associated with IV site duration, potassium chloride concentration, number of antibiotics, and solution osmolarity. Infusions started by anesthesiologists and sites with no dressings were least likely to be symptomatic. PMID- 2252402 TI - Methodological problems in the assessment of nurse-midwifery practice. AB - Through a review of the past 30 years' literature that addresses the structure, process, and outcomes of nurse-midwifery care, the limitations inherent to the study of nurse-midwifery are identified. The need for a prospective study that represents the diversity of nurse-midwifery practice patterns and incorporates an appropriate control group is acknowledged. Difficulties inherent in the design and statistical analysis of such a study are discussed. PMID- 2252403 TI - Reliability and validity of the Popovich Scale in home health care assessments. PMID- 2252404 TI - Interrater reliability of the Apgar score in term and premature infants. PMID- 2252405 TI - Differences in volunteer and randomly acquired samples. PMID- 2252406 TI - Involving practicing nurses in research. PMID- 2252407 TI - The proliferation of unreliable and invalid questionnaires. PMID- 2252408 TI - Bleeding time: a guide to its diagnostic and clinical utility. PMID- 2252409 TI - Hematology reference ranges. PMID- 2252411 TI - Is there a plethora of pathologists? PMID- 2252412 TI - A response to challenge for the College of American Pathologists' new Q-Probes program. The impact of whole-blood testing on response time. PMID- 2252410 TI - The Anasazi connection. PMID- 2252413 TI - The origin of primary tumors of the atrioventricular node. Resolving an old controversy. PMID- 2252414 TI - College of American Pathologists-Centers for Disease Control collaborative study for evaluating reference materials for total serum cholesterol measurements. AB - Several recent studies to evaluate the performance of laboratory instruments have shown that with some instrument systems processed (lyophilized, frozen, and stabilized) materials exhibit matrix effects that cause the assay for cholesterol to respond differently for them than for patient specimens. To understand this phenomenon better the College of American Pathologists, Northfield, III, and the Centers for Disease Control, Atlanta, Ga, have conducted a collaborative study with 44 laboratories where 16 instruments manufactured by nine companies are evaluated. The purposes were to assess measurement variation on several reference materials used for standardizing total cholesterol measurements and to evaluate a new stabilized liquid serum as a potential reference material. Lypophilized, frozen, fresh-frozen, and stabilized materials at three concentrations were measured for total cholesterol. The results show that the average coefficient of variation of measured total cholesterol for all instruments, laboratories, vials, and replicates is 3.6% to 4.1% for each of the materials measured (excluding the results for one instrument). For one instrument, however, significant bias was found on the stabilized liquid serum material. Results from the fresh-frozen materials indicate that the instrument systems evaluated allow laboratories to attain the National Cholesterol Education Program analytical performance goals. PMID- 2252415 TI - The 1988 comprehensive blood bank survey of the College of American Pathologists. AB - An average of 2211 laboratories reported results in this comprehensive blood bank survey. In general, the participant performance remains strong in ABO and D typing, unexpected antibody detection and identification, crossmatching, and antigen identification. However, certain samples achieved less than the usual performance levels. In one sample, anti-C, which was not present, was reported by many participants. In a third sample, only 90% of the participants correctly recorded that no antibody was detectable. Two cross-match challenges did not reach the required participant consensus for grading purposes. The ungraded samples and the supplementary questions provide mock clinical situations and are used to determine current practices and procedures in transfusion medicine. The results of these studies and the participant responses are included. PMID- 2252416 TI - An analysis of outcome following percutaneous transluminal coronary artery angioplasty. An autopsy series. AB - We analyzed autopsy findings on 26 patients who died following percutaneous transluminal coronary angioplasty (PTCA). Twenty-one patients died within 3 weeks of undergoing PTCA; demonstrable cardiac complications were found in 19 patients: platelet-fibrin thrombi (10 patients [48%]), coronary artery dissections (17 patients [81%]), thromboemboli (13 patients [62%]), atheroemboli (seven patients [33%]), and myocardial infarcts (17 patients [81%]). An increased incidence of coronary platelet-fibrin thrombi was noted when compared with a non-PTCA cardiac autopsy population (five of 53 patients). Apparently there was an increased incidence of coronary atheroemboli and thromboemboli in the patients with coronary platelet-fibrin thrombi (eight patients) when compared with patients who did not have platelet-fibrin thrombi (five patients), although this was not statistically significant. There was no evidence of a systemic hypercoagulable state or of disseminated intravascular coagulation. The pathogenesis of this is unclear; however, vasospasm and a disruption of the endothelial surface induced by PTCA with subsequent platelet activation are possible causes. Although not statistically significant, there was a proponderance of female subjects (seven patients) and an increased incidence of diabetes mellitus (six patients) and hypertension (13 patients) when compared with a control population of all patients undergoing PTCA at The Cleveland (Ohio) Clinic Foundation in 1987, suggesting that diabetes mellitus, hypertension, and female sex may be clinical risk factors for fatal complications following PTCA. PMID- 2252417 TI - Pulmonary capillaritis and glomerulonephritis in an antineutrophil cytoplasmic antibody-positive patient with prior granulomatous aortitis. AB - A 59-year-old man showed asynchronous development of noninfectious granulomatous aortitis with aneurysm, followed 9 months later by pulmonary capillaritis and glomerulonephritis in association with elevated serum antineutrophil cytoplasmic antibody levels. To our knowledge, the combination of large artery vasculitis and small vessel systemic vasculitis (capillaritis) has not been previously reported. This case may represent a hybrid type of systemic vasculitis combining features of giant cell arteritis and Wegener's granulomatosis. PMID- 2252418 TI - The distribution of enkephalins in human carotid bodies showing cellular proliferation and chronic glomitis. AB - Human carotid bodies obtained at necropsy that showed prominence of either the sustentacular cell or the dark variant of chief cell or chronic carotid glomitis were studied by an immunogold labeling technique. The peptides methionine and leucine enkephalin had a similar distribution to that found in the normal human carotid body. They were localized prominently and predominantly in the dark and progenitor variants of chief (type I) cells. The sustentacular (type II) cells showed no immunoreactivity for the enkephalins. Cell counts on immunolabeled chief cells in cases of sustentacular cell hyperplasia and chronic carotid glomitis were found to be at the lower end of the normal range, whereas those in dark cell prominence occurred nearer the upper limit. PMID- 2252420 TI - Normal reticulin level in iliac bone marrow. AB - While the level of marrow reticulin may be a factor that is used when the presence of a hematologic disorder is being considered, to our knowledge no study has graded the amount of reticulin present in normal iliac bone marrow. Grading reticulin stains of bone biopsy specimens from 100 hematologically normal patients documented that the normal amount of reticulin in the marrow is low. Twenty-seven percent of the patients had marrow reticulin grade 0 using the Bauermeister scale, 42% had grade N, 27% had grade 1, and 4% had grade 2; no patient had a Bauermeister grade 3 or 4 reticulin level. Knowledge of the normal range of reticulin is essential when the reticulin level is used as a factor in evaluating the possibility of a hematologic disorder. PMID- 2252419 TI - Intestinal metaplasia is age related in Barrett's esophagus. AB - The correlation among cellular characteristics of Barrett's esophagus, patient age, and malignant neoplasm is not well documented. This study, which describes a population of 66 patients with Barrett's esophagus spanning 1 to 80 years of age, analyzes the cellular constituents of their lesional tissues by endoscopic biopsy and histochemical and morphometric studies. Goblet cell metaplasia, identified in 50% (n = 14) of pediatric patients, increased significantly to involve 84% (n = 32) of biopsy specimens from adult patients with Barrett's esophagus. This increase was exponential by linear regression analysis (R2 = .64) between the ages of 5 and 29 years. Pediatric patients usually had 25 or less goblet cells per square millimeter of Barrett mucosa with no identifiable epithelial dysplasia or cancer; Nissen fundoplication lessened esophageal inflammation, but the Barrett mucosa persisted. Goblet cell metaplasia maintained a plateau (mean of 57 cells per square millimeter of Barrett mucosa) between the ages of 41 and 80 years. Dysplasia, in situ carcinoma, or invasive carcinoma was found in patients with Barrett's esophagus who were aged 41 years or older. This study demonstrates persistence of Barrett mucosa, increased incidence of goblet cell metaplasia, and predictable changes in goblet cell number with advancing patient age. The relationship between Barrett mucosa and malignant neoplasm remains uncertain, but the goblet cell may serve as a marker of disease chronicity in which setting neoplasia evolves. PMID- 2252421 TI - Lymphoproliferative disorders associated with carbamazepine. AB - Carbamazepine-induced lymphoproliferative disorders are relatively rare. A 32 year-old woman developed cervical lymphadenopathy while taking carbamazepine. Histologic evaluation of the lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture by a population of pleomorphic immunoblasts. The predominant cell population expressed CD3, CD2, CD5, and CD4, while results of testing for CD8 were negative. On the basis of the morphologic and immunohistologic features, a diagnosis of high-grade, non-Hodgkin's lymphoma, T cell immunoblastic type, was made. Despite the fact that aggressive behavior is usually associated with immunoblastic lymphomas, the patient has done well for 33 months after cessation of carbamazepine in the absence of chemotherapeutic treatment. The clinical features of this patient's illness, therefore, suggest that it is best regarded as a so-called pseudolymphoma. PMID- 2252422 TI - Enhanced expression of c-myc and H-ras oncogenes in Letterer-Siwe disease. A sequential study using colorimetric in situ hybridization. AB - Tissues from two patients with disseminated histiocytosis X (Letterer-Siwe disease) in which histiocytosis X cells exhibited histologic and cytologic features of malignancy were evaluated by in situ hybridization with the use of biotinylated nucleic acid probes to c-myc and H-ras oncogenes. Enhanced expression of these oncogenes was observed in mononucleated and multinucleated cells of histiocytosis X in the terminal proliferative phase but not in the early quiescent phase of Letterer-Siwe disease in both patients. Our findings indicate that deregulation of c-myc and H-ras in histiocytosis X are late events that likely confer a selective growth advantage to histiocytosis X cells. PMID- 2252423 TI - Monocytoid B-cell lymphoma in a patient with human immunodeficiency virus infection. Demonstration of human immunodeficiency virus sequences in paraffin embedded lymph node sections by polymerase chain reaction amplification. AB - There is a significantly increased incidence of malignant lymphoma in patients with acquired immunodeficiency syndrome (AIDS). The lymphomas are usually of a high grade and of B-cell phenotype. While the frequent presence of reactive monocytoid B lymphocytes in patients with AIDS-related lymphadenopathy has recently been documented in several studies, to our knowledge, there are no reported cases of monocytoid B-cell lymphoma, the neoplastic counterpart of monocytoid B lymphocytes, in patients with AIDS. We now describe a human immunodeficiency virus (HIV)-positive patient with HIV-related lymphadenopathy in whom monocytoid B-cell lymphoma developed during the course of his disease. The morphologic and immunologic features of the lymphoma were characteristic of monocytoid B-cell lymphoma, and the involved lymph node exhibited a reversed CD4/CD8 ratio. Moreover, using the polymerase chain reaction, we were able to demonstrate HIV genome in DNA extracted from the lymph node tissue. To our knowledge, this is the first report of a case of monocytoid B-cell lymphoma occurring in an HIV-positive patient and in which we were able, by using a sensitive molecular biologic technique, to demonstrate HIV sequence in paraffin embedded, fixed lymph node sections. PMID- 2252424 TI - Pulmonary malakoplakia in a patient with the acquired immunodeficiency syndrome. Differential diagnostic considerations. AB - Malakoplakia is an unusual inflammatory condition characterized histopathologically by accumulations of benign macrophages, or von Hansemann's cells, that are associated with diagnostic intracellular and extracellular calcospherites, termed Michaelis-Gutmann bodies. Currently believed to represent an acquired defect of macrophage digestion, malakoplakia most commonly occurs in the urinary tract and is associated with a variety of infectious agents, notably gram-negative bacilli. We describe a patient with the acquired immunodeficiency syndrome who presented with a cavitating lingular mass. A transbronchial biopsy specimen revealed pulmonary malakoplakia, the seventh reported case of this condition and the second reported occurrence of pulmonary malakoplakia in a patient with acquired immunodeficiency syndrome. Microbiological cultures were positive for Rhodococcus equi. The significance of this finding, and the differential diagnosis of intra-alveolar histiocytic proliferations in patients with acquired immunodeficiency syndrome, is discussed. PMID- 2252425 TI - Disseminated Conidiobolus infection with endocarditis in a cocaine abuser. AB - A crack cocaine abuser developed disseminated infection caused by a species of Conidiobolus not known to cause disease in vertebrates. The fungus gained entry via skin abrasions on the lower extremities, spread through the hematogenous route, and caused endocarditis. There was evidence of fungal infection in the lungs, heart, kidneys, skeletal muscles, and brain. An additional complication was extensive rhabdomyolysis, with a marked elevation of creatine kinase of up to 1.2 million U/L. PMID- 2252426 TI - Hepatic cyst associated with Peutz-Jeghers syndrome. AB - A solitary hepatic cyst, associated with Peutz-Jeghers syndrome, is described. To our knowledge, this association has not been previously reported. A developmental anomaly or hamartomatous nature of this lesion is suggested. Knowledge of this association may be helpful in the clinical diagnosis of this benign entity. PMID- 2252427 TI - Soft-tissue tumor with abnormal amianthoid collagen fibers. AB - Electron microscopic examination of a solitary soft-tissue tumor from the face demonstrated large areas with abnormal amianthoid collagen fibers in the neoplasm. The lesion was classified as a benign neoplasm of myofibroblasts and tentatively named a myofibroblastoma. The significance of the amianthoid collagen fibers is unknown. Normal native collagen fibers were found in some parts of the neoplasm. PMID- 2252428 TI - Extramedullary hematopoiesis in a bronchial carcinoid tumor. An unusual complication of agnogenic myeloid metaplasia. AB - A case of bronchial carcinoid tumor with foci of extramedullary hematopoiesis is presented. The patient had a 6-year history of agnogenic myeloid metaplasia and hepatosplenomegaly. All three hematopoietic cell lines were represented in different areas of the bronchial tumor. To our knowledge, this is the first case of extramedullary hematopoiesis described in a bronchial carcinoid and only the fourth report of hematopoietic cells in a neoplasm of otherwise unrelated origin. The pathogenesis of this uncommon finding is discussed and the literature is reviewed. PMID- 2252429 TI - Sponge artifact in biopsy specimens. AB - We describe a sponge-induced artifact in histologic sections of small biopsy specimens. The artifacts are angulated, often triangular holes within the tissue. They appear to be introduced as individual sponge barbs become embedded in the perimeter of biopsy specimens during tissue processing. The artifact is generally of little importance, but in certain specimens, such as needle biopsies of the kidney or liver, it may occasionally obscure important information. Other methods, such as lens paper wrapping, may be superior in these situations. The utility of the tissue cassette sponge, in most situations, outweighs the artifact. PMID- 2252431 TI - Sense and antisense oligonucleotides. PMID- 2252430 TI - From Army Medical Museum to National Museum of Health and Medicine. A century-old institution on the move. PMID- 2252432 TI - [Functional and morphological characteristics of the digestive reaction of gastric mucosa]. AB - Morphological state of connective tissue (stromal) cells of the stomach mucous membrane has been studied in healthy persons, having a habitual regime of feeding. During digestive period in the stomach mucous membrane, certain changes develop, which are considered as a digestive reaction. Three stages of the digestive reaction, having strict morphological signs are determined, their connections being stated by means of morphometry and mathematical analysis. I stage (preparatory) is characterized with a moderate vascular reaction, degranulation of mast cells under the superficial++ epithelium of the mucous membrane, with a moderate neutrophilic leukopedesis and a moderate lymphocytic infiltration; II stage (developed) is distinguished as a definitely demonstrated reaction of the microcirculatory bed, intensive degranulation of mast cells at all levels of the mucous membrane, massive discharge of neutrophilic granulocytes and lymphocytes into stroma; III stage (restorative) is characterized with a predominance of fibroblasts and fibrocytes, with reparation of mast cells, with decreasing saturation of stroma with neutrophilic granulocytes, lymphocytes, an increased number of eosinophilic granulocytes takes place. The data obtained widen our knowledge on functional morphology of the stomach mucous membrane, normal and at gastroduodenal pathology. PMID- 2252433 TI - [Morphofunctional changes in the lymph nodes and microcirculatory bed of small intestinal mesentery of dogs in septic peritonitis after endolymphatic administration of ampicillin]. AB - With the aim to study effectiveness+ of endolymphatic (EL) administration of ampicillin (AC), using the model of an acute diffuse septic peritonitis in dogs, the morphological and morphometrical investigation has been performed concerning the state of the lymph nodes (LN), which are regional as regards the pathological focus (pelvic) and remote (tracheobronchial, mesenteric) and hemomicrocirculatory bed (HMCB) of the small intestine mesentery. All LN groups studied are involved in the pathological process, that produces certain increasing disturbances in the structure and cell composition in LN. In 6 h the changes are especially manifested in the pelvic LN, and in 18 h--in the animals without application of AC, or at its intramuscular injection LN lose their typical structure. Their dimensions and number of lymphoid nodules++ and medullary cords decrease, a sharp impoverishment of lymphocytes in LN is observed. By this time critical disturbances in the HMCB structure develop; they are characterized as presence of great amount of avascular areas in the mesentery, extended capillary loops, plasmatic saturation of interstitium. When AC is injected endolymphatically, simultaneously with peritonitis modelling T- and B-dependent zones in LN are preserved, a high volumetric part of lymphocytes is kept in all groups of LN, structure and function of HMCB are normalized. The pronounced delay in development and decreasing manifestation of infective-toxic disorder in LN and HMCB depend on effective concentrations of the antibiotic, produces in the lymphatic system. PMID- 2252434 TI - [Synaptic structure of human cerebral cortex in chronic hypoxia and epileptic changes in the brain]. AB - Comparative quantitative analysis of the synaptic pool of the neuropil in the molecular layer at the temporal epilepsy and cerebral chronic hypoxia (brain tumor, that is not accompanied with a convulsive syndrome) has been performed using biopsy material. As a control the brain of practically healthy persons, who died a sudden death, has been used. The contrasting method of the phosphoric tungsten acid alcohol solution and OsO4 has been applied. An essential complication in the cerebral cortex synaptic structure in the zone with a regular epileptic activity, as well as preservation of quantitative density of synapses near to the control level at epilepsy have been revealed. At the chronic hypoxia simplification in organization of interneuronal connections at the level of synapses and reduction in the quantitative density of synapses have been noted. The complication of the cerebral cortex synaptic structure and epileptic changes++ of the brain is considered as an increase in the neuropil informativity, contributing to keeping a long-term memory about the character of epileptic manifestations. PMID- 2252435 TI - [Morpho-chemical characteristics of the brain of rats genetically predisposed to catalepsy]. AB - Cell organization of the cerebral cortex and striatum has been studied by+light optics and enzymatic activity of neuromediators catabolism--histochemically. In layers III and V of the sensomotor cortex and in the nucleus caudatus the number of neurons per unit area is increased, and their size is decreased. Volume of cytoplasm and nuclei of neurons in both layers is decreased, the latter--to less extent. The total amount of the perineuronal glia in the nucleus caudatus is also decreased at the expense of astroglia. In the cerebral cortex it is equal, but the ratio between astro-++- and oligodendroglia is changed. Acetylcholinesterase activity in the layers III and V of the sensomotor cortex is lower than in the control, while monoamine oxidase activity is kept at the control level. The genetically determined anomalies++ of growth and development of the cerebral cells is supposed to be considered as a structural base of the cataleptic state. PMID- 2252436 TI - [Localization of leu enkephalin in animal and human brain stem]. AB - At investigating brains of humans, rabbits and pigeons by means of the cytochemical method, using peroxidase-++--antiperoxidase complex, an immune positive reactivity to ++leu enkephalin has been revealed in neurons of the substantia nigra, in the grey substance of the aqueduct area, in the posterior nucleus of the cochlear nerve, in the ventral part of the giant-cellular reticular nucleus in the nucleus of the solitary tract and in capillaries of the brain also. By means of some ultrastructural investigations certain places have been determined where synapsis and deposition of neuropeptides take place. These are specialized endotheliocytes, pericytes and neurons, situating especially close to the capillary wall. PMID- 2252437 TI - [The cell theory--history, present state and prospects (on the 150th anniversary of the development of the cell theory)]. AB - The main stages of history of this most important biological conception are presented and the state of the modern cell theory and its future prospects are considered. Since 1839, when T. Schwann expounded his conception of the cell, a long pathway in cognition of the cell function and organization has been covered. From the original picture of the complex organism as a "cellular state", made up of relatively independent "elementary organisms", i.e. cells the modern biology has come to the idea of the cell as an integral system either being a part of a complex organism, or living free in the nature (protists). The cell represents certain qualitatively peculiar level in a complex evolutionary established hierarchy of biological systems. Some particular tight relations, existing between cytology, as a fundamental biological science and molecular biology, genetics, ecology and other biological disciplines are considered. The importance of the cell conception is ascertained for practical aims, especially in medicine. PMID- 2252438 TI - [Manifestations of the mobility of sensory neurons of the spinal ganglion after stimulation of its peripheral receptors]. AB - The body of sensory neurons in the frog spinal ganglion++ possesses an active mobility. This is demonstrated as pulsation and changes in its form. The mobility is closely connected with electrogenesis of cells. When an irritation is applied (press of a needle, or application of acetylcholine on the urinary bladder receptors), the neurons of the node respond with an increasing rate of impulse activity. Simultaneously, the mobility of these neurons increases. The character and form of their mobility in response to mechano- and chemoirritation differ from each other. Possible mechanisms of connection between the form of the cell body mobility and the character (active or passive) of its electrogenesis are considered. The mobility of the neurons, together with other morphological signs (tinctorial peculiarities and some others) can serve as an indication of their functional state without application of electrodes in morphological experiments. PMID- 2252439 TI - [Studies of human skin by cryofractographic and electron-microscopic methods]. AB - Ultrathin slices from the human abdominal skin and platinum-carbonic replicas, obtained by means of the freeze-fracture method have been studied electron microscopically. Transmembranous proteins are revealed on the membrane surface as membrane-bound particles with the diameter 5-7 nm. They mainly concentrate on the membrane protoplasmic surface. Certain difference is noted in distribution of tonofibrils in cytoplasm of the epidermal cells, when various methods for preparation of specimens to be investigated are used. Predominance of the freeze fracture method comparing to the routine method of electron microscopy is discussed, since the specimens do not subjected to fixation, dehydration and resin saturation. PMID- 2252440 TI - [Morpho-functional characteristics of lymph nodes in mice of different strains after administration of immunomodulators]. AB - Using certain histological and morphometrical methods, cytoarchitectonics of T- and B-zones in the iliac lymph nodes have been studied with a simultaneous embryometry at a physiological pregnancy and under conditions of immunomodulators (IM) administration. The degree of influence of IM changes in the raw polysaccharide++-conjugate-polyelectrolite. Mass of the lymph nodes studied under effect of polyelectrolite becomes greater. Polyelectrolite and conjugate stimulate essentially the hormonal link of immunity and activate the system of mononuclear phagocytes. Morphofunctional state of the iliac lymph node changes more considerably at polyelectrolite administration and somewhat less--at conjugate, with the greatest degree in pregnant mice, in comparison with nonpregnant ones. The IM produce hypertrophy of the lymph node, making a stimulating effect in lymphatic nodules++, paracortical zone cortical plateau, medullary cords, medullary intermediate sinus, as well as in cellular reactions (blast transformation++, amount of macrophages and plasma cells having various degree of differentiation, bi- and multinuclearity). Parallelizm between rearrangement degree of the iliac lymph node, administration of the synthetic IM and growth of the fetus mass has been revealed. This stresses the volume of reserved plastic properties of the lymph node and possibility to make longer the period of its greatest activity up to termination of pregnancy when IM are introduced. Pregnancy is a sensibilizing factor, which intensifies (or prolongates) the reaction of T- and B-zones in the lymph node and its cell composition. IM, altering the maternal immunological status, produce certain changes in the fetus mass. PMID- 2252441 TI - [Anatomy and topography of extra-organic lymphatic vessels and regional lymph nodes of human prostate]. AB - The work has been performed on 50 complexes of the small pelvis organs of men at the age of 22-88 years. The interstitial injection of Gerota mass has been used. The extra-organic++ lymphatic vessels (LV) get out of the lateral surfaces and base of the gland. Their amount varies from 2 up to 14, diameter 0.1-1.5 mm. Three directions of LN course have been detected. The regional lymph nodes are external, internal and common iliac, superior and inferior rectal and lumbar lymph nodes. Dimensions of the area where the regional lymph nodes are situated, are defined. PMID- 2252442 TI - [Histo-topography of the lymphoid tissue of children's trachea]. AB - By means of certain microscopical methods areas from the middle third of trachea have been examined in children, died from various causes not connected with diseases in the pulmonary pathways. At birth in the mucous membrane of the trachea there is no lymphoid tissue. Its elements in a small amount appear at the initial stage of the suckling period. In two-month-old infants the first signs of lymphoid perinucleoli appear. During the early period of infancy the main regions of the lymphoid cells localization are clearly defined, in the area of some ducts of the tracheal glands including. In children, whose age corresponds to the first period of childhood, lymphoid accumulations have a pattern, resembling similar structures of the trachea in mature persons and the greatest concentration of cells, in comparison to the preceding groups of children in the ages examined. PMID- 2252443 TI - [Manifestations of adaptive processes in the epithelium of the renal glomerular filter]. AB - Fifteen kidney biopsy samples+, obtained from children suffering from the primary nephrotic syndrome, characterized with a high selective proteinuria and non inflammatory character of changes in the renal corpuscles have been investigated after hormonotherapy (11 cases before and 4 cases 2-3 weeks after it). In podocytes certain disturbances in the lysosomal-vascular apparatus develop with a successive appearance of degeneration, desquamation and even necrosis of these cells. After prednisolone++ treatment edema of cytoplasm of the cells and their processes disappears, amount and size of the filtration slits are partly restored. PMID- 2252444 TI - [Characteristics of liver regeneration after vagotomy]. AB - Peculiarities of a reparative process in the hepatic parenchyma have been studied after toxic effect of CCl4, at vagotomy in 1, 2 and 4 weeks after the operation. Appearance of a more massive lesion and decreasing regeneration of the vagotomized liver have been revealed. The proliferative activity of hepatocytes, normal and after vagotomy has a principally similar character and is described as a curve with two picks, having its maximum on the 2nd and the 5th-6th days after xenobiotic administration. The intensity of the hepatocyte proliferative activity in the denervated liver essentially surpasses that in the control and decreases, as the area of the parenchymal lesion decreases in the latest time after the operation. PMID- 2252445 TI - Albendazole therapy for neurocysticercosis. PMID- 2252446 TI - Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results. AB - Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period. PMID- 2252447 TI - White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study. AB - T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252448 TI - Tuberculous meningitis. Short course of chemotherapy. AB - In March 1986, we began a 6-month short course trial of therapy for tuberculous meningitis, in which 28 patients were analyzed. The diagnosis was based on the following cerebrospinal fluid test results: in 53.5% of the cases, Mycobacterium tuberculosis was identified by direct smear; in 57%, culture in Lowenstein-Jensen medium was positive; in 83.3%, the detection of anti-bacille Calmette-Guerin (BCG) antibodies by enzyme-linked immunosorbent assay was positive; and in 74%, the dosification of adenosine deaminase activity was positive. In addition, in 21.4% of the cases, the diagnosis was established by means of autopsy findings. Moreover, the diagnosis was supported by bacteriological analyses from another tissue or body fluids. Despite the administration of an antituberculous therapy, 32.4% of the patients died: all of the decreased had reached the last stage of the disease by the beginning of treatment. Sixteen percent of the patients who survived after more than 18 months of follow-up after therapy had ended suffered neurological sequelae. With the 6-month therapeutic regimen, the morbidity/mortality is similar to that found in the longer-course therapies. The latter regimen is therefore thought to be a good and acceptable therapeutic option for the treatment of tuberculous meningitis. PMID- 2252449 TI - Clinical and positron emission tomographic studies in the 'extrapyramidal syndrome' of dementia of the Alzheimer type. AB - Extrapyramidal signs, particularly rigidity and tremor, have been reported in a proportion of patients with dementia of the Alzheimer type. To test the hypothesis that these extrapyramidal signs are similar clinically and neurochemically to the extrapyramidal signs of Parkinson's disease, a group of 20 patients satisfying clinical criteria for probable Alzheimer's disease were studied and assessed clinically for the presence of rigidity, tremor, and bradykinesia. In those patients with extrapyramidal signs, qualitative differences were observed between the signs in these patients and in subjects with Parkinson's disease. Fifteen of 20 patients underwent fluoro-18-dopa scans, which showed no significant difference in fluoro-18-dopa uptake into the caudate and putamen between normal subjects and the rigid and nonrigid patients with Alzheimer's disease, in contrast to the marked reduction in fluoro-18-dopa uptake into the putamen that is observed in Parkinson's disease. This provides clinical and in vivo neurochemical support for the hypothesis that extranigral factors may be involved in the pathogenesis of rigidity in Alzheimer's disease. PMID- 2252450 TI - Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features. AB - Four patients with the clinical syndrome of primary progressive aphasia and a nonfluent aphasia profile were followed up over a period of 3 to 5 years. Extensive neuropsychological data for three patients revealed a progressive, quantitative decline of language with relative stability of memory, visuospatial skills, and reasoning. Comportment and most activities of daily living were preserved even when speech was unintelligible. Although several aphasia types may be associated with primary progressive aphasia, a nonfluent aphasia profile and phonemic paraphasic errors are most useful in differentiating it from the much more common clinical syndrome, "probable Alzheimer's disease." The clinicopathological correlates of probable Alzheimer's disease differ from those associated with primary progressive aphasia. Therefore, the clinical distinction between the two syndromes may be important for predicting the underlying pathophysiologic changes during the life of the patient. PMID- 2252451 TI - Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery. AB - The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease. PMID- 2252453 TI - Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy. AB - We tested patients with progressive supranuclear palsy and control subjects on a task of visuopatial attention. Targets preceded by cues on the same side were termed validly cued; and those on the opposite side, invalidly cued. For all subjects, validly cued targets were responded to faster than those that were invalidly cued. The difference between reaction times for invalidly and validly cued targets, which is hypothesized to measure attentional movement, was significantly increased for the patients. The performance of the controls on certain neuropsychological tests was correlated with their attentional ability. These correlations were altered by progressive supranuclear palsy. Physostigmine treatment of the patients induced a speeding of responses to invalidly cued targets as a function of the duration of the disease. These studies show defects in cognition and attention in patients with progressive supranuclear palsy and demonstrate that physostigmine reduces some of the abnormal visual attentional performance. PMID- 2252452 TI - Reduced cerebral blood flow in early stages of human immunodeficiency virus infection. AB - In order to determine if brain perfusion abnormalities, which are known in patients with acquiredimmunodeficiency syndrome dementia, occur in early stages of human immunodeficiency virus infection, technetium 99m hexamethyl propyleneamine oxime-single-photon emission computed tomography studies were performed in 20 patients infected with human immunodeficiency virus who belonged to Walter Reed stages I through IV. None of these patients demonstrated signs of dementia or severe neurological dysfunction. Pathological patterns of hexamethyl propyleneamine oxime uptake were seen in 14 patients, seven of whom had normal results during neurological examination. Only four patients had signs of cerebral atrophy on cranial computed tomographic scan. These data suggest that subtle changes in cerebral perfusion seem to arise early in the course of human immunodeficiency virus infection and may indicate human immunodeficiency virus encephalopathy before neurological symptoms or noticeable structural damage occurs. PMID- 2252455 TI - Aspirin and stroke. PMID- 2252454 TI - The Physician's Health Study. A neurologist's concern. PMID- 2252456 TI - Aspirin and the primary prevention of myocardial infarction and stroke. PMID- 2252457 TI - Reminiscences. On running a small department. PMID- 2252458 TI - [Chemistry and clinical significance of human plasma proteins]. AB - Enormous progress has been made in the course of the past few years in the various fields of plasma protein research. The primary and disulfide bridge structures are now known for almost all of the 120 proteins thus far isolated from human plasma, including trace and ultratrace proteins as well as a number of genetic variants. Genetic cloning and the derivation of the amino-acid sequence from the nucleotide sequence have played a decisive role here. However, we are only in possession of the exact three-dimensional structure for a small number of plasma proteins. The major problem in this respect is, at present, the lack of suitable protein crystals for X-ray structure analysis. We still do not know the physiological function of a large number of plasma proteins, despite the fact that they, in part, have been well characterised both physically and chemically and could be assigned to their respective protein families on the basis of their amino-acid sequence. The development of techniques for protein structure determination is relatively well advanced today, yet we lack methods of illuminating the structure-function relationship. There are more than 20 different highly purified protein preparations in virus-safe form available today for substitution therapy. To this effect new purification procedures have been developed which pay particular attention to virus elimination and inactivation. Should present indications be confirmed, one may assume that further plasma proteins (e. g. proteinase inhibitors, apolipoproteins, fibronectin) could be of significance in therapy and prophylaxis. Unlimited amounts of human blood are not available. Gene technology offers a promising alternative, at least for the production of plasma protein administered to patients in small amounts. Work is being done intensively on various blood coagulation factors and proteinase inhibitors at the moment, and factor VIII: C is already being successfully used for the treatment of patients with hemophilia A. However, it will no doubt take years before recombinant plasma proteins are in a position to extensively replace traditional preparations. In the field of diagnostic investigation with plasma proteins immunochemical methods of determination have assumed an increasing significance during the course of the last two decades. Particularly the development of automated techniques which allow serial quantification of individual proteins, has made protein profiling for diagnosis and monitoring in a number of diseases a routine procedure in many clinical laboratories. PMID- 2252459 TI - [Hemostasis, fibrinolysis, proteolysis: interaction with inflammatory reactions]. AB - Many physiological processes are based on the finely regulated interaction between cells and enzymatic reaction cascades. Mainly proteinases are involved in these processes, which are regulated by inhibitors, principally proteins. If this sensitive balance is disturbed, uncontrolled pathophysiological events can be induced, which are often associated with inflammatory reactions. Characteristic for inflammation are events like contact activation of hemostasis, increasing permeability of blood vessels caused by activation of the Kallikrein-Kinin- and the Complement-system and Plasmin-release induced by activation of fibrinolysis. The following uncontrolled proteolysis, leading to tissue destruction, is mainly associated with the degree of illness. Inflammatory cells excrete besides proteinases also mediators maintaining and increasing these processes. Only when the balance between proteinases and inhibitors is restored, inflammation subsides. Afterwards the controlled course of physiological reactions is possible again. PMID- 2252460 TI - Molecular biology of proteins involved in blood coagulation. AB - Normal hemostasis in humans requires the interaction of a large number of plasma glycoproteins with blood platelets and vascular endothelial cells. Many of the plasma glycoproteins which participate in blood coagulation are zymogens of enzymes that interact in a stepwise manner in a series of reactions. In the last years most of these glycoproteins have been purified from human plasma by standard techniques. Some of them are used as therapeutics for restoring coagulation disorders. The knowledge about the plasma proteins involved in blood coagulation was greatly increased after cloning and sequencing of the respective complementary DNAs. Furthermore, recombinant DNA technology is used for the alternative production of several coagulation factors. It is the aim of this article to give an overview about the molecular biology of the enzymes and cofactors involved in blood coagulation. PMID- 2252461 TI - [In vitro and in vivo efficacy of a toxin-neutralizing human staphylococcal immunoglobulin]. AB - The pathogenic relevance of alpha-hemolysin of Staph. aureus in human infections is up to the present in discussion. Numerous therapeutic human trials to modify the outcome of a Staph. aureus infection by giving passively hyperimmune sera did not clarify the situation. First the work of Bhakdi22 has provided us with a rational approach for a systemic use of specific immunoglobulin preparations. A highly purified Staph. aureus alpha-hemolysin was carefully detoxified and injected into volunteers. From these sera were collected by plasmapheresis and a 5S immunoglobulin was prepared. In preclinical trials the antitoxin efficacy was evaluated. We examined in vitro cultures of human thrombocytes and monocytes, and of porcine pulmonary arterial endothelial cells. As in vivo models we used the intoxication of mice and monkeys and an intradermal test in rabbits. In all these models we were able to demonstrate the high antitoxic efficacy of a human anti alpha-hemolysin-5S-immunoglobulin preparation. PMID- 2252462 TI - Physiochemical features of monoclonal idiotype-anti-idiotype complexes: importance of inter-chain disulfides for size distribution patterns and molecular geometries. AB - Cyclic tetramers represent the preferentially formed complexes of a murine monoclonal idiotype-anti-idiotype (Id-anti-Id) system consisting of IgG antibodies or (Fab')2 fragments at micromolar concentrations. The cleavage of inter-chain disulfides of both Id and anti-Id caused the predominant generation of cyclic dimers at the expense of larger aggregates, suggesting with regard to already published data that the hinge located interheavy-chain disulfides are essential for the strain. PMID- 2252463 TI - Development of an ELISA for the detection and determination of contaminating proteins in recombinant DNA derived human erythropoietin. AB - An enzyme linked immunosorbent assay (ELISA) has been developed for the quantitative determination of the most probable contaminating proteins (MCP) of recombinant human Erythropoietin produced in the mouse fibroblast cell line C 127. The developed ELISA is a double polyclonal sandwich type immunoassay, which allows a quantitation of the MCPs in the range of parts per million. The polyclonal antibody, used for both coat and conjugate in this ELISA, was demonstrated to be reactive with the reference MCPs (a collection of the most probable protein contaminants) by immunoblot analysis and immunoabsorption of radiolabeled MCPs. Affinity purification of this antibody preparation using the immobilized MCPs resulted in an assay with higher signal-to-noise ratio. The assay was demonstrated to be very specific for the MCPs obtained from the rhu EPO purification process. Since the purification of each recombinant DNA derived protein expressed in mammalian cells requires its own unique process, no generic assay for contaminating proteins can be developed. There are only a few common criteria for the development of such multi-antigen ELISA, which will be discussed in this paper. PMID- 2252464 TI - Development of monoclonal antibodies for therapeutic drug monitoring. AB - For the development of multilayer fluorescent immunoassays to determine directly a variety of therapeutic drugs high specific monoclonal antibodies against the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproic acid have been prepared. For each antibody a standard curve could be established showing good linearity and a suitable sensitivity scope. To validate the eligibility of the desired antibodies a variety of drugs and metabolites sharing structural similarities to the individual drugs were tested for their cross-reactivity. It could be shown that only a few very closely related compounds exhibited substantial cross-reactivity. These monoclonal antibodies are therefore assumed to be suitable for a TDM-assay development. PMID- 2252465 TI - [Problems in standardization of the immunochemical detection of plasma proteins. I. International reference standards for plasma proteins. II. Immunochemical relation of measurement signals and values]. AB - When the results of plasmaprotein determination--dependent on the reagents, methods and other factors--are expressed in international units (IU) a better comparison of the results between different labs is possible. By this means and using the corresponding reference values and reference intervals the reliability of the interpretation of laboratory data will increase. The situation regarding the WHO IRP's for plasma proteins (approx. 20 parameters) and the relation from IU to mg in the reagents of the Behringwerke AG are reported. The overlability of WHO IRP's has not allowed yet to achieve an optimal standardization of the immunochemical methods for measurement of plasma proteins. This depends especially on the complexity of the antigen-antibody reaction. The relationship between the measured signal and the hence obtained value will be discussed in details in the second part of this paper. Hereby especially the reciprocal interdependence between physicochemical properties of proteins and the deriving immunochemical behaviour as well as the dependence of the results from the quality of the antibodies-containing reagents are also considered. Possible solutions for a better control system of the plasma protein determination by using the so called master calibrators as internal support for validation will be presented. Furthermore, general immunochemical postulates and rules for optimization of the standardization of plasma protein determination will be proposed and discussed. PMID- 2252466 TI - Token economy approaches for psychiatric patients. Progress and pitfalls over 25 years. PMID- 2252467 TI - Family interventions for schizophrenia. AB - Studies that have attempted to reduce schizophrenic relapse by the use of family interventions are described. Results from studies that implemented behavioral family interventions with patients who were identified as high risk because of the expressed emotion status of their relatives have demonstrated that relapse rates can be significantly reduced over a 2-year postdischarge follow-up period. A number of ongoing studies, especially those that are investigating the interaction of family interventions and different medication regimes, are also discussed. Areas for further investigation are identified, for example: the use of multiple outcome measures, the use of single-case studies and the development of ideographic assessment measures, the interaction of biological and environmental influences, the alleviation of the burden of care, the involvement of the consumer in services, the development of behavioral formulations and analysis of family engagement and compliance, staff training in intervention methods, and the translation of research results into clinical practice. PMID- 2252468 TI - Behavioral family treatment for patients with bipolar affective disorder. AB - Techniques of behavioral family management (BFM), which have been found to be highly effective in delaying relapse for schizophrenic patients when used as adjuncts to medication maintenance, are also applicable in the outpatient treatment of recently hospitalized bipolar, manic patients. The authors describe their adaptation of the educational, communication skills training, and problem solving skills training modules of BFM to families containing a bipolar member. The observations that families of bipolar patients are often high functioning, and that these families seem to enjoy interchanges that are highly affective and spontaneous, led to certain modifications in the original BFM approach. The authors found it necessary to be (a) more flexible and less didactic, (b) more oriented toward dealing with affect and resistance to change, and (c) more focused on the patient's and family members' feelings about labeling, stigmatization, and medication usage. Research issues relevant to testing the efficacy of this approach are also discussed. PMID- 2252469 TI - Social and independent living skills for psychiatric patients in a prison setting. Innovations and challenges. AB - There is a tremendous need for mental health services in correctional settings. An innovative psychosocial rehabilitation program that emphasizes skills training has been implemented by a state mental health agency within a large state prison. Preliminary results indicate that the treatment is effective in teaching social and independent living skills to mentally ill inmates. However, durability of treatment effects ultimately depends on the ability to track and to provide follow-up services for inmates after they are discharged to the general prison facility or to parole settings. Recommendations for developing and implementing effective systems of delivering mental health services in prisons are offered. PMID- 2252470 TI - Teaching conflict resolution skills to the chronically mentally Ill. Social skills training groups for briefly hospitalized patients. AB - Previous research on social skills training has demonstrated its usefulness as an adjunct treatment for a variety of psychiatric disorders. At the Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, an acute-care psychiatric hospital, a social skills training group has been in operation for over 3 years. The group is unique in its format in several ways that are described in this article. Data collected over the 3-year period are also presented. The major findings indicate that even over a very brief period of time during an acute hospitalization, patients can learn basic conflict resolution skills. Some predictors of skill acquisition were also identified. PMID- 2252471 TI - Spermatocytic seminoma associated with rhabdomyosarcoma. AB - A case of spermatocytic seminoma intimately associated with rhabdomyosarcoma is reported. The patient, a 51-year-old man, presented with a two-year history of right-sided testicular enlargement. Orchiectomy was performed, and a large testicular tumor was excised. Further investigations during hospitalization revealed lung, liver, and retroperitoneal lymph node metastases. Further therapy was refused, and the patient died at home two months after orchiectomy. Autopsy was not permitted. Although the great majority of spermatocytic seminomas occur in pure form, do not metastasize, and have very good prognosis, in addition to the present case, seven cases of spermatocytic seminoma associated either with rhabdomyosarcoma or undifferentiated sarcoma have been reported. Presence of the sarcomatous element is associated with aggressive behavior, metastatic disease, and very poor prognosis. It is considered that the sarcomatous element develops from the spermatocytic seminoma by anaplastic transformation. PMID- 2252472 TI - Clinical and biochemical correlates in primary amyloidosis. PMID- 2252473 TI - [Tobacco- and alcohol-associated cancer risk of the upper respiratory and digestive tract]. AB - A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in the ENT Departments of the University hospitals of Heidelberg and Giessen (FRG) provided information on the role of chronic tobacco and alcohol consumption as risk factors in 200 patients and 800 control subjects (4:1 matched design).--Only 4.5% of the tumour patients were non-smokers in contrast to 29.5% in the control group. The average tobacco and alcohol consumption in the patients was more than twice that high than in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer.--It could be demonstrated that tobacco as well as alcohol increased the risk for head and neck cancer, in a dose-dependent fashion, as separate risk factors. In heavy smokers (greater than 60 pack years) a relative risk of 23.4 (alcohol-adjusted) was calculated. For heavy drinkers (greater than 100 g ethanol/day) a relative risk of 21.4 (tobacco-adjusted) was documented. Combined alcohol and tobacco consumption showed a synergistic effect and increased the cancer risk more in an multiplicative than in an additive manner: A daily ethanol consumption of more than 75 g/day combined with more than 50 pack years caused a risk value of 146.2. PMID- 2252474 TI - [What happens to vocal cord dysplasias in variable smoking behavior?]. AB - The influence of smoking with regard to the development and course of laryngeal dysplasias was examined. The case histories of 63 patients with histologically proven dysplasias of the larynx were evaluated in the light of their answers to a questionnaire covering their lifetime smoking habits. RESULTS: 1. The percentage of smokers in the patient group significantly exceeds the percentage of smokers in the general population. 2. The disease is more likely to lead to deteriorated histological findings in smokers. 3. A change in smoking habits at the time of diagnosis has no significant effect on the further course of disease. 4. Non smokers have higher levels of dysplasia at first biopsy, but the disease is less likely to progress. The development of malignancy was not observed in the non smoker group. PMID- 2252475 TI - [The tonsils as MALT (mucosa-associated lymphoid tissue) of the nasal mucosa]. AB - One of the most effective defense mechanisms of the nasal mucosa is its immune response leading to the synthesis of antibodies directed against inhaled antigens. In order to understand the immunology of the upper respiratory tract it is essential to know whether this response takes place within the mucosa itself or within regional lymphoid organs. The authors investigated cell populations involved in immune processes within the mucosa and as a model of a lymphoid organ, in the tonsil. Using a range of monoclonal cell surface markers, the authors concentrated on antigen-presenting cells, the B-cell differentiation, and T-cell subpopulations and their corresponding activation markers. The findings demonstrate that the normal mucosa has no organized lymphoid structures and few or no early, maturing, or activated B-lymphocyte stages. The antibody-producing plasma cells found within the mucosa can therefore not be regarded as locally formed. On the contrary, the palatine tonsils demonstrate a typical lymphoid structure and contain all activation and differentiation stages of B-lymphocytes from premature to plasma cells. This would suggest that the human nasal mucosa is not capable of providing a local immune response, but is dependent on lymphoid organs like the tonsil, as the regional "mucosa-associated lymphoid tissue" (MALT). PMID- 2252476 TI - [The effect of endonasal paranasal sinus surgery on lung function of patients with bronchial asthma]. AB - Lung function tests of 13 patients suffering from manifest asthma and of 4 patients showing only bronchial hyperreactivity were performed before and on an average of 12 months after endonasal surgery of the paranasal sinuses. In the four subjects, bronchial hyperreactivity was no longer detectable postoperatively by provocation with carbachol. Five asthmatics could stop medication of 1 to 3 of their drugs, five others were able to reduce the dosage of one of their drugs to 50% or more. Lung function and medication was unchanged in two asthmatic patients, one patient had to add a drug to his medication while showing an unchanged lung function. In patients with asthma and chronic paranasal sinusitis, endoscopic endonasal sinus surgery (together with flanking measures, e.g. septal correction) is able to improve antiasthmatic therapy in a high percentage. PMID- 2252477 TI - [Tumors of the parapharyngeal space. Topographical anatomy, diagnosis, therapy, literature review]. AB - The borders of the parapharyngeal space are formed of fasciae of muscular tissue. Its lateral border is formed by the bone of the mandible, while its cranial border is formed by the petrous bone. The initial symptoms of parapharyngeal tumors are diagnostically volatile because of the soft tissue contents of the parapharyngeal borders. For diagnostic reasons, it has to be decided whether to extirpate tumor immediately in order to obtain a specimen for histological evaluation or whether extensive presurgical examinations are necessary. Aside from multiple serological investigations for infectious diseases, these include all kinds of noninvasive morphological procedures such as CT scan, MR scan, transcutaneous and endoscopic B-mode sonography. In addition, invasive procedures such as arterial angiographies and the taking of specimens may be necessary in some cases. PMID- 2252478 TI - [Supraorbital tumor as manifestation of Jaffe-Lichtenstein fibrous dysplasia]. AB - We report on the case of a 16 year old white female who presented at our outpatient clinic with a swelling of the left supraorbital region. Histologically a fibrous dysplasia Jaffe-Lichtenstein was found. Diagnostic procedures, possible complications, adequate therapy and prognosis of this disease are discussed and compared with the relevant literature. PMID- 2252479 TI - [Changes in blood flow velocity in the basal cerebral arteries following neck dissection]. AB - Cerebral blood-flow velocities (cm/s) and pulse index (PI) were studied pre- and postoperatively in a total of 15 male patients following bilateral radical/functional (group A; n = 10) or unilateral radical neck dissection (group B; n = 5) using a 2 MHz-pulsed transcranial Doppler ultrasonographical system (TCD), with a transtemporal approach to the middle cerebral artery. Systolic and mean flow velocities were significant reduced with subsequent increases in PI during the first postoperative sonography in group A-patients while no significant differences in TCD date developed in group B. Blood-flow velocities and PI reached control values within three days. General hemodynamic and respiratory parameters did not influence the changes in TCD flow profiles with the exception of moderate increases in arterial CO2 during the early postoperative period. It is concluded that the reductions in blood-flow velocities and concomitant increases in PI reflect a heightened resistance to flow in the arterial cerebral vasculature. The decrease in cerebral vascular compliance suggests increases in the cerebral venous outflow following the resection of essential drainage pathways. However, TCD does not provide any information about the adequacy of cerebral blood flow. PMID- 2252480 TI - [Synchronous registration of vestibulospinal and vestibulo-ocular reflexes in rotatory stimulation]. AB - A comparative study of vestibulo-spinal and vestibulo-ocular reactions is presented in normal subjects and in patients with different vestibular lesions. Four our investigations the rotatory chair was prepared with a special equipment for the "Vertical Drawing Test" to achieve the simultaneous recording of the nystagmus and laterotorsion reactions. Analyses of the two reflexes demonstrated a rare independence between the vestibulo-ocular and vestibulo-spinal reactions despite a common stimulus. Further studies supplying additional information laterotorsion to nystagmus, may be helpful in the analysis of balance. Variations were found in the patterns of behaviour in different groups of vestibular disturbances. PMID- 2252481 TI - [Pneumocele of the frontal sinus]. AB - Pneumosinus dilatans frontalis is a rare condition of the frontal sinus. Although the aetiologic mechanism is not yet known, it is presumed that an increased intrasinusal pressure due to a check valve mechanism is responsible for this condition. By measuring intrasinusal pressure we demonstrated this mechanism. PMID- 2252482 TI - [A simple method for the demonstration of the bacterial spectrum in the nose and the nasopharynx in the infection-free interval in children with adenoid hypertrophy]. AB - The implications of bacterial colonization and distribution patterns in the nasopharynx and nasal cavities of children with adenoidal hypertrophy without clinical signs of acute infection are to be determined. We examined the spectrum and distribution of the facultative pathogenic bacterial flora in nasal cavities and nasopharynx of children with clinical apparent symptoms or signs of adenoid hypertrophy in an infection free interval. Compared with the nasal cavity we found an accumulation of pathogenic bacteria in the nasopharynx. A transnasal single swab from the nasopharynx showed to be the most effectively practical way to detect clinically relevant pathogenic bacteria. A thin flexible calcium alginate swab was used in our experiments. Swabbing from the anterior nasal cavities proved to be a minor successful diagnostic method. PMID- 2252483 TI - [Hyperkinetic syndrome following premedication with Thalamonal]. AB - A rare hyperkinetic syndrome in a child after premedication with Thalamonal has been known for some time. The triad: unconsciousness, opisthothonus and conjugate deviation should be considered by surgeon and anesthetist and it looks like the somnolent-ophthalmoplegic-hyperkinetic type of Economo's Encephalitis lethargica. The therapy is simple: 1 ml Biperiden i.v. PMID- 2252484 TI - Score reporting for the 1991 Medical College Admission Test. AB - In December 1988, a 16-member advisory panel, made up of medical school deans, basic science faculty, clinical scientists, medical education researchers, medical students, premedical advisers, and practicing physicians, completed a full-scale review of the format, content, and score-reporting system of the Medical College Admission Test (MCAT). The advisory panel's recommendations will shape the MCAT to be introduced in 1991. Presented here are data the panel used in deciding to keep the score scale for the upcoming MCAT. Survey data on student selection practices in U.S. and Canadian medical schools and acceptance information for 1987 applicants showed that medical schools used the scores differently within each school and between the schools in deciding whom to admit. The data demonstrated the value of the current reporting system and led the advisory panel to recommend retention of the 15-point MCAT score scale in 1991. PMID- 2252485 TI - Score reporting on NBME examinations. AB - Because the National Board of Medical Examiners (NBME) will introduce new comprehensive Part I and Part II examinations in 1991, a review has been made of score reporting methods to be used in the new examinations. The review was conducted also because of concern expressed by some that NBME examination scores are misused in medical schools and in resident selection. In this paper, selected aspects of score reporting are defined, the uses of score reports outlined, and the potential for misuse described. It should be noted that the NBME is obliged to make available numerical scores to state medical boards and to examinees. Individual scores are reported to others only with the permission of the examinee. The results of an opinion poll conducted by the NBME of medical educators and medical students are presented. The range of opinion is broad but favors numerical score reporting and a designated pass/fail score. PMID- 2252486 TI - Physician manpower for rural America: summary of a WAMI region conference. AB - Although legislators have intermittently focused their attention on physician manpower issues, the needs of rural America for physicians remain unmet. These needs will not be met unless there is an adequate supply of physicians receptive to and appropriately trained for the challenges and opportunities of practice in a rural community. A declining interest by matriculating and graduating medical students in primary care practice makes it problematic that the needs of rural America can be met in the near future unless medical schools attempt to reverse the trends in medical students' specialty choices. In October 1989, the University of Washington School of Medicine conducted a working conference on physician manpower issues facing rural communities in Washington, Alaska, Montana, and Idaho. The discussions and conclusions of this conference about increasing the percentage of graduates entering rural practice apply to other regions of the country, and this paper summarizes the conference's recommendations. PMID- 2252487 TI - Using senior students as clinical skills teaching assistants. PMID- 2252488 TI - Making prevention a practical reality. PMID- 2252489 TI - Hard choices, no easy solutions. PMID- 2252490 TI - Survey research, or debunking the Q-sort. PMID- 2252491 TI - Job satisfaction of behavioral scientists in family medicine. PMID- 2252492 TI - The meagerness of physicians' training in emergency psychiatric intervention. AB - This study was undertaken to determine how much training physicians receive in emergency psychiatric intervention (EPI) during their residency programs. In 1988 the author mailed a questionnaire to 256 program directors of residencies in the major nonpsychiatry specialties. A total of 236 (92%) responded. Their responses indicate that emergency medicine and family practice residency programs provide the most training in EPI, followed by pediatrics, internal medicine, obstetrics gynecology, and surgery. But overall, EPI training was meager. The findings indicate that 75% of the programs never assigned EPI-oriented readings to the residents and 70% of the programs never gave lectures or seminars on that subject. The author concludes that EPI skills are frequently absent in current medical practice because physicians have not been taught these skills; he recommends that more training is essential and indicates what it might consist of. PMID- 2252493 TI - Variables influencing career choices of graduates of informatics programs funded by the National Library of Medicine. AB - Graduates of the National Library of Medicine-supported Medical Informatics (MI) training programs were studied to determine the variables influencing their choices of an academic or nonacademic career. More than 60% of the available population of trainees (171 of 272) were studied in 1986 and four of the nine variables measured by means of a questionnaire were significant in differentiating the choices the students made. The training programs located in a private institution, with the majority of the faculty from the medical school and with a small number of trainees who already had the M.D. or Ph.D. degree, generated the highest proportion of graduates seeking academic careers. Discriminant analysis was done to determine whether a combination of variables would discriminate between those who chose academic careers and those who did not. It indicated that the status of the institution (public or private); the entry degree of the trainee; and the productivity of the training program faculty were sufficient to correctly classify 75.3% (67 of 89) of the students who chose academics and 71.9% (59 of 82) of those who did not. There is now a baseline of data that can be used in future studies. PMID- 2252494 TI - Differences in professional activities, perceptions of professional problems, and practice patterns between men and women graduates of Jefferson Medical College. AB - Differences between men and women graduates of one medical school in practice patterns, professional activities, and problems were investigated. A questionnaire was mailed in 1986 to 600 physicians, randomly selected from 1,102 who had graduated from Jefferson Medical College of Thomas Jefferson University between 1977 and 1981. Four hundred fifty (364 men and 86 women) responded (75%). The women were less likely than the men to be employed full-time; however, proportionately more women than men held full-time academic appointments, treated patients from low-income families, and served in underserved areas in inner cities. The women reported working fewer hours per week and having fewer patients than did the men. The women published scientific articles as often as did the men but were less likely to serve on professional committees, receive professional awards, or develop medical procedures. The women were less concerned about the oversupply of physicians and malpractice litigation. Implications of the findings for health manpower planning and practice pattern expectations are discussed. PMID- 2252495 TI - Factors influencing the development of area health education centers with Texas Mexico border populations. AB - Area Health Education Centers (AHECs) have been viewed as an appropriate vehicle for implementing new initiatives for training health professionals who will work along the U.S.-Mexico border. Perceptions about this program in Texas were evaluated from July 1988 to June 1989 to identify problems and formulate suggestions that might be of use to academic health science centers (HSCs)--and in particular medical schools--working with Hispanic populations. Interviews were conducted with 116 people: the presidents and/or deans of all eight Texas HSCs and/or medical schools, other deans and faculty, community leaders in five border counties, and state officials. The school and community perspectives about past and present AHEC activities were compared. Some of the barriers were: insufficient components of the health care delivery system to support medical education in severely underserved areas; differing school and community priorities; cultural differences between the school faculty and the community; and feeling among community physicians and dentists that AHECs were a source of competition. The school and community respondents agreed that the AHEC program needs more cooperative planning and training that emphasizes public health education for future AHEC-like activities with border populations. PMID- 2252496 TI - Credentialing protocols used by internal medicine residency programs in New York State. AB - In the fall of 1988, the Association of Program Directors in Internal Medicine established a New York State (NYS) Task Force to assess the impact of the "Report of the New York State Ad Hoc Advisory Committee on Emergency Services- Supervision and Residents' Working Conditions." Fifty-eight of the 62 NYS internal medicine residencies were surveyed in 1989 and 21 provided copies of their credentialing protocols. Analysis of these protocols identified eight essentials of a viable credentialing protocol, including five present in a majority of the examined protocols. The study produced a master list of procedures with a corresponding range of certification criteria and confirmed most programs had undergone parallel development of remarkably similar protocols, suggesting that a uniform credentialing system was possible and warranted further study. PMID- 2252497 TI - Factors encouraging research productivity in a division of general internal medicine. AB - The authors investigated two of the causes of and possible remedies for low research activity (as measured by rate of publication) of faculty members in a division of general internal medicine at a university hospital and its affiliated Veterans Administration medical center. They did this by analyzing information about the faculty in the health center's records spanning a 16-year period. This 1989 study suggests that the general medicine faculty members who are also involved in subspecialties and who have protected research time can improve their research productivity. PMID- 2252499 TI - Evaluation of a program to train Saudi Arabian physicians. AB - The authors evaluated a program at the University of Calgary, in Alberta, Canada, that provided residency training for 11 Saudi Arabian physicians. Through a series of semistructured meetings in 1989 involving the Saudi residents, other residents in the program, members of residency training committees, faculty, and program directors, the program was reviewed to assess whether the Saudi physicians were prepared for the program and progressed satisfactorily when compared with the other residents, whether the training and evaluation were equivalent to those of the other residents, the advantages of the program to the university, and whether the university should be pursuing opportunities to train other foreign nationals. The interviews showed that there was variability in the preparation and progress made by the Saudi residents but the benefits to the university in providing training to a small group of carefully selected foreign trained physicians were greater than the disadvantages. The information gained during the review reinforced the need to do periodic examinations of training opportunities for foreign physicians and yielded recommendations for improving such training. PMID- 2252498 TI - Influences of marital status and parental status on the professional choices of physicians about to enter practice. AB - The trend toward increasing numbers of working women may alter the ways both men and women physicians structure their professional lives. The 1987 graduates of residency and fellowship programs at the University of Minnesota Medical School- Minneapolis were surveyed in June 1987 about professional plans and factors that led to their decisions. The women expected that their spouses would contribute half of their family's income, whereas the men expected that they would be largely responsible for their family's income. The married women with children planned on working fewer hours than did other physicians. Family structure may play an important role in preventing the convergence of men and women physicians' personal incomes or working hours. PMID- 2252501 TI - Teaching pediatrics residents how to give information to parents. PMID- 2252500 TI - Success in obtaining an orthopedics residency. PMID- 2252502 TI - A community internship as a continuation of a community-oriented curriculum. PMID- 2252503 TI - A subspecialty outpatient clinic experience for third-year medical students. PMID- 2252504 TI - An international health fellowship in primary care in the developing world. PMID- 2252505 TI - Teaching neonatal resuscitation using an advanced life support course and laboratory experience. PMID- 2252506 TI - Residents in COTH hospitals by specialty and selected characteristics, 1988. PMID- 2252507 TI - Come on in, the water's just fine. AB - Rural America is dynamic and challenging, and it is vastly different from what it was mid-way through the century. Unfortunately, many people, including policymakers, have a very outmoded picture of what today's rural America is really like. This paper begins by exploding seven common myths about rural America. Next, three characteristics of the rural environment--diversity, sparse population, and interdependency with broader social and economic forces--are examined in relation to health care delivery and medical education. The contribution of health care to the economic needs of rural America is also explored. The paper closes by noting both altruistic and self-serving motives for the medical education establishment to become more concerned and involved in rural health issues. PMID- 2252508 TI - Physicians for the American homelands. AB - Academic health centers in the United States are in danger of becoming more and more irrelevant to the non-tertiary, primary health care needs of modern society. This paper explores options to respond to one segment that repeatedly has been demonstrated to be in distress: rural health care. Recommendations are made about selective recruitment into medical and other health schools to address the issue, early professional socialization, curricular reform, and the types of technical assistance that academic centers might well provide to rural practitioners and caregiver institutions. PMID- 2252509 TI - Physician distribution and rural health care in the states. Part 2--State legislative summaries addressing physician distribution and rural health care, 1984-1989. PMID- 2252510 TI - Policy priorities for rural physician supply. AB - A number of efforts can be attempted in rural medical education initiatives in recruitment, socialization, curricular reform, and community technical assistance. Further work is needed in identifying strategies that are most appropriate and cost effective in different states and regions that may have different situations and needs. Careful consideration needs to be given to reasons why such ideas have not moved beyond the demonstration stage over the past 20 years; it is suggested that without substantial reform of payment systems favoring rural and primary care, educational reform will have marginal effectiveness and remain at the demonstration level. PMID- 2252511 TI - Rurally based education: confronting social forces underlying ill health. AB - Skills needed by physicians to address and prevent our communities' leading causes of premature death--injuries, cancer, cardiovascular disease, homicide, and suicide--are not in the typical roster of medical school learning experiences. And traditional, urban, hospital-based venues of medical education scarcely model for students appealing careers in the community. These twin problems are especially severe in rural America. Yet rural training sites are ideal locations for students to confront the array of social, political, and economic forces underlying ill health in our society. If learning in medical schools is to be suitable for rural practice, students must receive early and sustained exposure to rural communities and to rural physician role models. To facilitate this educational redirection, medical schools must (1) sensitize their existing faculty and residents to community health needs via in-service training on community health topics, (2) encourage faculty and residents to provide service and education outreach to rural communities, and (3) promote rural health research. Finally, to prevent the marginalization of rural health concerns within the academic agenda, efforts should be made to develop university-community partnerships in which model rural training practices and a "field" teaching faculty are established and nourished by the medical center. PMID- 2252512 TI - Graduate medical education and rural health care. AB - Currently, residency training is neither detrimental nor helpful to the problems of rural health. Based on four generally accepted "truths" about rural health, medical schools should recruit students from rural areas, have them choose family practice as a career, and train them in rural settings. Given no substantial changes in residency training, the following recommendations are made. Develop a consensus definition of "rural." Educate rural communities to the purpose of residency training. Residency review committees should support rural rotations of at least six months; consider the number of residencies at a site irrelevant for accreditation; judge the quality of the product as the standard of accreditation; and define teaching competency by other than specialty label. All medical school departments should be involved in seeking solutions to the problems of rural health. New opportunities for funding of rural residency training should be sought. If major changes in residency training are possible, internal medicine, family practice, and pediatrics should merge as a single primary care specialty and for residency training. Only this residency should be considered primary care for residency reimbursement purposes, and only its graduates should be reimbursed for primary care services. PMID- 2252513 TI - Residency training for rural primary care. AB - Student selection, curriculum, training environment, and special inducements should be considered in the attempt to increase the availability of primary care physician services to rural populations. Some controversial areas such as rural training sites, merging of primary care specialties, and compromise of the continuity experiences in residency are also addressed. Some basic philosophic differences in academic centers must be recognized. PMID- 2252514 TI - Medical education and the rural health crisis: a personal perspective from experiences in five states. AB - While there is good evidence that decisions regarding practice site are influenced by experience in medical school and residency, medical education constitutes only one of a complex set of factors that have made it difficult to recruit physicians to rural America. A solution to the rural health crisis will require not only changes in student selection, curriculum, and training location, but also strengthening of the rural economy, improved reimbursement to rural hospitals and primary care physicians, and increased sensitivity by leaders of the medical profession to the needs of rural areas and rural practitioners. PMID- 2252515 TI - Rural practice modes. AB - Solo practice is the dominant mode of rural medical care delivery. At the same time, it is the most likely not to succeed, because the solo physician is choosing to leave the rural community. Group family practice is the most stable form of rural practice, is acceptable, and is sought by the majority of family practice residents seeking to establish new practices. Characteristics of successful rural practices include group practice, retention of the same health care providers for more than three years, a community-oriented focus, integration of non-M.D. health care providers, and a commitment to education within the practice. Academic medical centers with area health education centers (AHECs) should consider developing expanded AHECs to provide the education, planning, consultation, and expertise now needed by rural communities. Academic medical centers without AHECs should consider creating offices of rural health to provide the education, planning, consultation, and expertise needed in rural communities. PMID- 2252516 TI - Rural health care--in the "future perfect". AB - Rural health care can thrive if innovative tactics are used. Four assumptions can influence how health care occurs in rural areas. One assumption is to view the world in a "both/and" view of human phenomena. Second is to recognize that competition is a dominant mode; and that using integrative/collaborative solutions could enhance all health care. Cultural ethnocentricity and professional ethnocentricity, the third assumption, are counterproductive. This is especially true in rural America. The fourth assumption, one can only accomplish what one can imagine, sets an infinite range of possibilities for rural health care. Education must change to incorporate a commitment to collaboration and to integrative, innovative solutions to problems. PMID- 2252517 TI - The National Health Service Corps: a partner in rural medical education. AB - Within the United States Public Health Service, the programs of the Bureau of Health Care Delivery and Assistance have played an important role in improving access to primary care services in rural America. In part, this has been accomplished through the administration of grants to assist in establishing systems of care and the assignment of National Health Service Corps (NHSC) health professionals. From a peak of over 1,600 NHSC-obligated scholarship recipients available for service in 1985, the number of available obligated practitioners has decreased to around 120 in 1990. A main focus of the NHSC has, therefore, necessarily changed from the placement of obligated health professionals to the recruitment of volunteers and increased emphasis on the retention of current providers. The systems of care that have been most successful in their retention efforts have been: group practices, composed of a nucleus of individuals who had been at the site for three to five years; community-oriented, utilizing non physician providers as part of the delivery team; and those committed to continued provider education. The NHSC has initiated programs to help increase the likelihood that medical students will choose a primary care career and spend all or part of that career serving those most in need. These programs include the National Medical Association Minority Mentor Network, the American Medical Student Association Health Promotion/Disease Prevention Program, the Commissioned Officer Student Training and Externship Program, and the American Academy of Family Physicians Residency Advocate Program. To meet the future needs for access to care in rural America, partnerships with academic centers must be enhanced and expanded. PMID- 2252518 TI - Academic support for rural practice: the role of area health education centers in the school of medicine. AB - An area health education center (AHEC) program offers a school of medicine a special way to improve the environment for professional practice in rural areas. An AHEC is a regional center for education and training that houses faculty and staff who teach students and residents while providing continuing education, consultation, and technical assistance for rural practices. With the support of outreach library services and visits by university-based faculty, AHECs help improve a rural community's ability to recruit, retain, and keep up-to-date primary care physicians and other health manpower. PMID- 2252519 TI - Osteopathic medicine and primary care practice: plan or serendipity? AB - General practitioners predominate in osteopathic medicine (57% of all D.O.s), as compared with allopathic medicine. A number of possible reasons are put forth: the student selection process (cloning by admission committee general practitioners); special features of osteopathic education (more required courses, primary care courses, and rotations); training in osteopathic hospitals (mainly community institutions); a required rotating internship; and predominant departments of general practice in osteopathic hospitals and colleges (providing more high-quality general practitioner role models). The author suggests consideration of personality differences, as measured by the Myers-Briggs Type Indicator, as a possible causative factor in differences between the allopathic and osteopathic segments of medicine. PMID- 2252520 TI - Education for rural health in Saskatchewan. AB - The Canadian Province of Saskatchewan, like its American counterparts, is experiencing a steady urbanization of its population particularly by young adults. This has been accompanied by progressive decrease in the availability of health services to an aging rural population. Physicians, and, in particular, Saskatchewan graduates, find rural practice unattractive. Unlike the American experience, level of income is not the issue. Not only is rural practice unattractive to Saskatchewan graduates, but medicine as a career is not attracting students from rural areas. The need for a comprehensive overall strategy ranging from recruitment to reorganization of rural health care is proposed. PMID- 2252521 TI - Physician distribution and rural health care in the states. Part 1--An overview of state legislative activity, 1984-1989. PMID- 2252522 TI - Spontaneous antibody-secreting cells against DNA and common environmental antigens in systemic lupus erythematosus. AB - Cells spontaneously secreting IgG or IgM antibodies to DNA or to common environmental antigens--influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans--have been enumerated by ELISA spot in blood from patients with systemic lupus erythematosus (SLE) and normal donors. Mean values were raised for all antigens in the disease, with those for DNA being no greater than for the other antigens. In normal donors, levels of IgM-secreting cells were similar for DNA and the environmental antigens whereas virtually no IgG anti-DNA secreting cells were found. When results were expressed relative to total numbers of IgG or IgM-secreting cells, the differences between the groups disappeared or were greatly reduced in all systems except IgG anti-DNA. These findings are consistent with a requirement for both polyclonal activation and a self-antigen response in the production of IgG autoantibodies in SLE. PMID- 2252523 TI - Cross-reactivity of monoclonal anti-DNA antibodies with heparan sulfate is mediated via bound DNA/histone complexes. AB - To study in more detail the cross-reactive binding of anti-DNA antibodies to heparan sulfate (HS) and heparan sulfate proteoglycan (HSPG) purified from glomerular basement membranes (GBM), the binding pattern of 31 murine IgG anti DNA MoAbs, derived from MRL/lpr, NZB/W and graft-versus-host diseased mice, was analysed. In ELISA we found binding of 10 anti-DNA MoAbs to HS. Seven of the 10 anti-HS positive clones bound to HSPG but not to the HSPG core protein in ELISA and/or on Western blots. However, DNase-I treatment partly reduced this binding, whereas after purification of MoAb by protein-A sepharose chromatography under dissociative conditions, all clones completely lost their binding capacity to HS and HSPG. Culturing of hybridoma cells in the presence of 3H-thymidine revealed DNA bound to the MoAb. Although the binding to HS and HSPG could be reconstituted by the addition of the protein-A column effluent, this was not possible by the addition of DNA alone. Therefore, we performed immunoprecipitation of the effluent with purified MoAb and subsequent SDS-PAGE which showed that the complex also contained histones. However, histones alone were also not able to reconstitute the binding to HS and HSPG. It is concluded that binding of anti-DNA MoAb to HS and GMB-HSPG is mediated via bound complexes containing both DNA and histones. A comparable reaction with polyclonal anti-DNA Ab might play a role in the pathogenesis of SLE nephritis, since histones have a very high affinity for HS, the major glycosaminoglycan of the GBM. PMID- 2252524 TI - Differential effects of cyclosporine A on Langerhans cells and regulatory T-cell populations in severe psoriasis: an immunohistochemical and flow cytometric analysis. AB - Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions. PMID- 2252525 TI - Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type. AB - Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control. PMID- 2252526 TI - The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients. AB - In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compared to conventionally treated patients was observed at the third (0.17 +/- 0.06 vs 0.44 +/- 0.08 IU/kg/BW; P less than 0.02) and at the sixth month of therapy (0.19 +/- 0.07 vs 0.54 +/- 0.07 IU/kg/BW; P less than 0.005). Two patients ceased to require insulin therapy within the BW; P less than 0.005). Two patients ceased to require insulin therapy within the first month, showing a prolonged restoration of B-cell function. Serum C-peptide values were also significantly higher in the Ig-treated group compared to the control group after 3 and 6 months. As regards immunological parameters, patients showed a decrease in insulin antibody levels and a reduction in TAC+ cells. Intravenous Ig therapy seems able to affect positively the first phases of metabolic and immunological deterioration of Type I diabetes. PMID- 2252527 TI - Prednisone administration in recent onset type I diabetes. AB - The aim of our study was to investigate the efficacy of prednisone to preserve pancreatic beta-cell function in patients with recent-onset Type I diabetes mellitus (IDDM). Twenty-five patients with IDDM, aged 24 +/- 6 years, entered the trial within 8 weeks of the onset of diabetes. They were allocated, according to a single blind randomized protocol, to one of the following treatments: (A) prednisone (15 mg/day), (B) indomethacin (100 mg/day), (C) placebo. All treatments lasted 8 months and all patients achieved satisfactory metabolic control with a multi-injection regimen (three injections/day) within a few weeks, and maintained it throughout the entire period of observation. Only minor side effects were observed in the prednisone-treated patients. A lower insulin requirement was observed in the prednisone group than in other patients at 12 months (0.33 +/- 0.11 vs 0.57 +/- 0.06 U/kg/day, P less than 0.05), 18 months (0.34 +/- 0.11 vs 0.64 +/- 0.06, P less than 0.05) and 24 months (0.38 +/- 0.10 vs 0.63 +/- 0.05, P less than 0.05). Endogenous insulin release, evaluated as urinary C-peptide, was higher in the prednisone group than in other patients at 3, 6, 9, 12, 18 and 24 months (P less than 0.05). ANOVA confirmed differences among the three groups. Our study indicates that prednisone administration, at low doses and for a long period of time, effectively restored endogenous insulin release in IDDM patients. PMID- 2252528 TI - Lymphocyte transfusion in recent onset type I diabetes mellitus--a one-year follow-up of cell-mediated anti-islet cytotoxicity and C-peptide secretion. AB - In 19 patients with newly diagnosed Type I diabetes mellitus a single transfusion of 1.9 x 10(9) to 1.5 x 10(10) lymphocytes was performed. Fifteen Type I diabetic patients who did not receive a transfusion were used as controls. Anti-beta-cell cell-mediated cytotoxicity was measured using an insulin release assay. Stimulated C-peptide secretion (100 g glucose orally, 1 mg glucagon i.v.) was used to estimate residual beta-cell function. Both parameters were measured prior to transfusion and after 12 months. The transfusions were followed by a fall of cytotoxicity below the 95% confidence limit of the controls in 11 of the 19 patients ('responders') (15.7 +/- 1.7 ng insulin/islet/20 h vs 6.7 +/- 1.3 P less than 0.001), while the other eight transfused patients ('non-responders') (13.5 +/- 1.9 vs 17.1 +/- 2.9, ns) and the non-transfused control patients (11.6 +/- 1.1 vs 14.2 +/- 2.4, ns) displayed persistently high cytotoxicity levels. In the responder group a slight improvement in stimulated C-peptide secretion was observed (136 +/- 43 pmol/dl vs 148 +/- 38, ns) whereas in the non-responder (127 +/- 28 vs 106 +/- 25, ns) and in the control group (130 +/- 17 vs 97 +/- 19, P less than 0.05) the stimulated C-peptide responses declined during the 12-month follow-up. Thus, lymphocyte transfusion may have beneficial effects by suppressing anti-beta-cell cytotoxicity and preserving C-peptide secretion. PMID- 2252529 TI - Early administration of an immunomodulator and induction of remission in insulin dependent diabetes mellitus. AB - A clinical trial was undertaken to determine whether intensive thymopentin administration enhances remission of insulin-dependent diabetes (IDDM) during the first year after diagnosis. Dosage with insulin was minimized with target control of blood glucose levels less than or equal to 7.8 mmol/l before meals. Remission was defined as a prolonged period after IDDM onset (not less than 3 months) characterized by a non-insulin-receiving (NIR) state in which target metabolic control was reached without administration of insulin and with a valid C-peptide response, evaluated after standard breakfast. Sixteen IDDM patients aged 12-31 years, recruited within 2 weeks of initiation of insulin therapy and within 5 weeks of onset of symptoms, were treated with intravenous (i.v.) thymopoietin32 36 pentapeptide (Thy) (1 mg/kg/body weight) for 7 days and twice per week for up to 3 months. A control IDDM group without initial significant differences in metabolic control parameters was also studied. No difference was observed between the two IDDM groups regarding the after-diagnosis normalization curve of HbA1c; mean daily glycemic level rates and ICA titer decreased during the observation. A reduction in anti-insulin antibodies (AIA) in Thy-treated patients was observed in comparison to conventionally treated IDDM starting from 6 months and reaching a reduction peak at 1 year (P less than or equal to 0.02). As regards the NIR remission rate, it was significantly more accelerated in Thy-treated patients, reaching 43% at 6 months and 57% at 1 year vs 12% and 6.7% respectively in the control IDDM group (P range less than or equal to 0.05-0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252530 TI - Risk of progression to diabetes of low titer ICA-positive first-degree relatives of type I diabetics in southern Germany. AB - In a prospective study to evaluate the prevalence and predictive potential of circulating cytoplasmatic islet cell antibodies (ICA) and competitive insulin autoantibodies (CIAA), we screened 406 non-diabetic first-degree relatives of patients with Type I diabetes mellitus (n = 154 for CIAA). The prevalence of ICA was 2.5% (10/406) and of CIAA 0.6% (1/154) in ICA- and 10% (1/10) in ICA+ relatives at initial screening. The titer of ICA positivity in all relatives varied between 1:1 and 1:4. Values of elevated CIAA were 256 nU/ml of the CIAA+/ICA+, and 97 nU/ml of the CIAA+/ICA- relatives (normal range less than or equal to 39 nU/ml). Sera for repeat ICA and CIAA determination was obtained, and 70% of relatives were found to be again ICA+ after 1.5 years, 40% after 3 years, and 10% after 5.7 years. Both CIAA+ relatives were found to be again CIAA+ on follow-up. Intravenous glucose tolerance tests (IVGTT) were performed in all antibody-positive relatives. No decrease in first-phase insulin secretion (1 + 3 min) below the 1st percentile was observed in any of the ICA+ relatives during follow-up. No ICA+, but one CIAA+/ICA- relative had developed Type I diabetes after 5.6 years of follow-up. In summary, these results indicate that low titer ICA (less than 40 JDF units) are often transient and relatives with low titer ICA rarely progress to Type I diabetes. Elevated CIAA appear to be constant over time and associated with increased progression to overt diabetes. PMID- 2252532 TI - Identifying the pre-diabetic state in type I diabetics: condition for early intervention. PMID- 2252531 TI - Insulin requirements and residual beta-cell function 12 months after concluding immunotherapy in type I diabetic patients treated with combined azathioprine and thymostimulin administration for one year. AB - An increase in clinical and functional remissions with immunosuppression, as well as abnormal T-cell function, in Type I diabetic patients has been reported in the early stages of diabetes. A controlled trial with azathioprine and thymostimulin in separate and combined administration was performed in 45 recently diagnosed Type I diabetic patients. Phenotyping of the T-lymphocyte subsets, levels of CD25 positive cells and interleukin-2 production by patients' lymphocytes, as well as remission rate and stimulated C-peptide levels, were serially assessed. Remission was defined as mean weekly glycemic profiles less than or equal to 7 mmole/l, serial HbA1 values in the normal range and no insulin requirements for at least 2 consecutive months. At 3,6,9 and 12 months of immunotherapy, remission occurred respectively in 0%, 8.3%, 16.6% and 0% of the conventionally treated diabetic controls and in 42.8%, 50%, 42.8% and 36.2% of the subjects submitted to combined azathioprine and thymostimulin administration. Patients receiving azathioprine or thymostimulin alone did not achieve better remission rates than controls. C peptide levels were significantly higher (above 0.6 pmol/ml) in patients with remission than in those not in remission (P less than 0.02) throughout the trial. Excessive interleukin-2 production in recently diagnosed diabetics returned to normal levels in patients in remission. In the group receiving combined therapy, 38.5%, 25% and 23% were still in clinical remission at 6, 9 and 12 months after drug withdrawal. Twelve months after stopping treatment, patients who had remitted exhibited significantly lower insulin requirements and greater endogenous insulin secretion than those who had not remitted; the former also maintained near normal glycemic control. No side effects were detected except mild and transient leucopenia in a reduced number of patients receiving azathioprine. Remission was related to the time of beginning immunotherapy after the onset of diabetes (17.1 +/- 7 vs 42.5 +/- 15 days; P less than 0.01) and to age (17.7 +/- 5.6 vs 13 +/- 7 years; P less than 0.05). Interleukin-2 production seems to be negatively associated with clinical remission in the early stages of diabetes. Results suggest a complementary effect of the drugs used in this study that may enhance long-term remission in recently diagnosed Type I diabetic patients. PMID- 2252533 TI - Applying 100 millimetre and digital technology to general radiography. PMID- 2252534 TI - Imaging of the lumbar spine in spondylolysis and spondylolisthesis. PMID- 2252535 TI - Individual performance review. PMID- 2252537 TI - Radiography education meets the challenges. PMID- 2252536 TI - Low cost equipment for rapid throughput chest radiography. AB - Reorganisation within Harrow Health District in 1987 resulted in chest services being centralised at Northwick Park Hospital, and during the planning period much thought was given to choosing cost effective equipment capable of a throughput of a minimum of 30 patients per hour. The equipment that has been installed is based on a Transworld DCX-100 MSP1 dedicated chest unit, and is currently the only unit of its kind installed in the UK. After two years of use it is now possible to make comments on the benefits and drawbacks of the system, and this article may be of particular interest to managers of imaging departments in district general hospitals where value for money with low capital outlay is an important consideration. PMID- 2252539 TI - Choosing a radiological management system. PMID- 2252538 TI - Computers and nuclear medicine. PMID- 2252540 TI - Interventional radiography--child's play. PMID- 2252541 TI - Alpha-melanocyte-stimulating hormone immunoreactivity in melanoma cells. AB - Using a radioimmunoassay specific for alpha-melanocyte-stimulating hormone (alpha MSH), significant levels of immunoreactivity were detected in a range of murine and human melanoma cell lines, including a series of ras-transfected melanocytes. The levels found in the melanoma cell lines tested varied, and overall were higher than in non-melanoma cell lines assayed for comparison. Furthermore the highest levels of immunoreactivity measured tended to be in the least differentiated and most metastatic melanoma lines. High performance liquid chromatography showed a peak of immunoreactivity which co-migrated with a desacetyl alpha-MSH standard. Additional unidentified components of immunoreactivity were found, including a high molecular weight form revealed by Sephadex-G50 gel exclusion. These may represent bound alpha-MSH or fragments of the proopiomelanocortin precursor having in common the C-terminus epitope recognised by the antibody. In view of the known effects of alpha-MSH on anchorage independent growth and metastasis of melanoma cells, our findings raise the possibility that MSH peptides may have an autocrine role in the growth and progression of melanoma. However, further characterisation of the immunoreactive species is required to determine whether these represent biologically active forms. PMID- 2252542 TI - Expression of human epithelial characteristics in late passages of interspecific somatic hybrids derived from normal and hand wart keratinocytes. AB - The expression of epithelial features has been investigated from the 9th to the 30th passage in cells derived from the fusion of mouse 3T3.4E cells with normal or hand wart human keratinocytes. These cells stratified and grew either on plastic or collagen substrate without modifications. Such growth characteristics are similar to those observed in the epidermis. The doubling time of hybrid cells is nearer to that of 3T3.4E than to that of keratinocytes. Some epithelial markers were detected by immunofluorescence staining. Bullous pemphigoid antigen characteristic of the basal keratinocyte was detected, and cytoplasmic antigen of basal cells was positive with BL7 monoclonal antibody. Among the antigens of the suprabasal cell layers of the epidermis, the pemphigus antigen was present in all hybrids; epidermal keratins recognized by the monoclonal antibodies KL1 and KL2 were detected in wart hybrids up to the 9th passage. When hybrids were cultured in delipidized serum or in methylcellulose, few cells (less than 10%) reacted with KL2. Karyological analysis revealed both murine acrocentric and human submetacentric chromosomes. Thus, hybrid cells obtained from normal and wart keratinocytes were new cell types with a phenotype between keratinocytes and 3T3.4E cells. PMID- 2252543 TI - Differential expansion of human endothelial monolayers on basement membrane and interstitial collagens, laminin and fibronectin in vitro. AB - In this study the ability of a human endothelial cell monolayer to expand over specific components of the basement membrane and extracellular matrix was investigated over a 5-day period. The method was intended as a model to study the mechanisms of endothelial regeneration. All components were coated onto sterile coverslips at a concentration of 10 micrograms/ml. The highest expansion was obtained on fibronectin, laminin and collagen type III, all three being statistically significantly greater than on the uncoated control surface (0.002 greater than p greater than 0.0001). Collagens types I and IV and a high molecular weight fragment mixture of type IV (IV-F, consisting of 75, 120 and 140 kD fragments) elicited approximately similar expansion rates, significantly higher than the control (0.02 greater than p greater than 0.003), although significantly lower (approximately 15%) than collagen type III, fibronectin and laminin (p less than 0.001). The high monolayer expansion on collagen type III is surprising, as it is a relatively minor biosynthetic product of the endothelial cell. It could, however, be of significance in wound healing, in which endothelial cells come into contact with this interstitial collagen. In addition, the similar results obtained with collagens IV and IV-F indicate that expansion of the endothelial monolayer is not dependent on the integrity of the tetrameric structure of type-IV collagen. PMID- 2252544 TI - Immunologic effects of interleukin-2 adoptive immunotherapy in humans: acute in vitro anergy, in vivo antibody response to tetanus. AB - In a previous study we evaluated the in vitro immunologic responses of 14 patients receiving immunotherapy with either interleukin-2 (IL-2; 3 x 10(6) units/m2) or IL-2 plus lymphokine-activated killer (LAK) cells over a 45-day period. Blastogenic responses to mitogens or antigens were found to significantly decrease. Pokeweed mitogen immunoglobulin production decreased or showed no change. Multitest skin test response decreased during and after therapy. We concluded that, although natural killer and LAK activity are enhanced during therapy, in vitro blastogenic or immunoglobulin tests using mitogens or antigens for patients undergoing IL-2 immunotherapy have no predictive values and are depressed. In this study, we provide information that patients while receiving IL 2/interferon-alpha immunotherapy demonstrate as in the previous study in vitro reduced immunologic responses by at least 60%; however, in vivo, they had a normal immunoglobulin response to a tetanus booster. The disparity in results (in vitro versus in vivo) is unexplainable. Further analysis of other in vitro and/or in vivo tests is required to determine the effect IL-2 immunotherapy may have on the immune response status. PMID- 2252545 TI - Effects of cadmium on the energy metabolism of isolated hepatocytes: its relationship with the nonviability of isolated hepatocytes caused by cadmium. AB - The effects of cadmium on the energy metabolism of mitochondria were studied with isolated hepatocytes and rat liver mitochondria. It was found that cadmium inhibited the respiration of both isolated hepatocytes and mitochondria and decreased the ATP content of isolated hepatocytes. This inhibition of energy metabolism of mitochondria was highly related to the nonviability of isolated hepatocytes caused by cadmium. The site of electron transport of the mitochondrial respiratory chain blocked by cadmium was located between cytochrome b and flavo-proteins. The uncoupling effects of mitochondrial oxidative phosphorylation caused by cadmium may have resulted from changes in the fluidity and permeability of the mitochondrial membrane. PMID- 2252546 TI - Investigation of the amount of dissolved iron in food cooked in Chinese iron pots and estimation of daily iron intake. AB - The amount of dissolved iron in food cooked in Chinese iron pots and that in food cooked in aluminum, stainless steel, and clay pots were determined. It was found that the amount of dissolved iron in food cooked in Chinese iron pots was two to five times higher than that in food cooked in the other types of pots. According to the test results, the estimated increase in daily iron intake was about 14.5 mg for adults and 7.4 mg for children when Chinese iron pots were used. PMID- 2252547 TI - Studies of the genotoxicity of glycidyl methacrylate (GMA). AB - The following experiments were conducted to evaluate the genotoxic effects of GMA (glycidyl methacrylate) on mammalian and human cells. (1) Using the absorption spectrum shift method in vitro, we observed that the maximums of calf thymus DNA and GMA were shifted toward longer wavelengths (a change of more than 15 nm) and the absorbance decreased after incubation at room temperature for 15 min or more. The result indicates that binding of DNA and GMA had occurred. The binding force is strong, not affected by the addition of concentrated sodium chloride solution, and only slightly decreased by the addition of 8 M urea solution. Therefore the bond between DNA and GMA might be covalent. (2) In cell cultures, unscheduled DNA synthesis (UDS) in human and/or rat lymphocyte was induced and DNA semiconservative replication was inhibited by GMA at concentrations of less than 5.2 mM. (3) Sperm abnormality tests and assays of UDS in germ cells of male mice were conducted to study the in vivo genotoxicity of GMA. The results revealed that GMA could damage DNA, increase sperm abnormality frequency, and reduce the number of sperm cells. PMID- 2252548 TI - Detergent-induced changes in the protein constituents of various cell types of opercular epidermis of Rita rita. AB - Fish (Rita rita) were exposed to an anionic detergent, dodecylbenzene sodium sulfonate, at a concentration of 6.9 mg/liter (96-hr LC50 of the detergent). A series of histochemical techniques, used in this study for the demonstration of various protein constituents, indicated a gradual decrease in the intensity of staining reactions of the cytoplasmic material, suggesting a loss of protein moieties from the club cells and the epithelial cells of the opercular epidermis as a result of detergent exposure. PMID- 2252549 TI - The lead-chelating effects of substituted dithiocarbamates. AB - The effectiveness of certain substituted dithiocarbamates in mobilizing lead from preexposed rats was investigated. The animals received 10 mg Pb/kg/day, intragastrically, for 8 weeks and were treated thereafter with 400 mumol/kg, intraperitoneally, of morpholine dithiocarbamate, tetraammonium ethylenediamine diacetic acid dithiocarbamate (EDDTC), ammonium diethanolamine dithiocarbamate (ADDTC), sodium diethyldithiocarbamate, N-benzyl-D-glucamine dithiocarbamate (NBGDTC), or dimercaptosuccinic acid, daily for 5 days. All the chelating agents were effective in lowering the hepatic and renal burden of Pb. ADDTC, EDDTC, and NBGDTC were also able to lower the long bone Pb content. The lowering of Pb burden had no relationship to restoration of Pb-induced hematopoietic alterations. The relatively lower lipophilicity of substituted dithiocarbamates, owing to the presence of hydrophilic groups, seems to be advantageous in preventing passage of metal chelate into the brain. None of the substituted dithiocarbamates caused excessive excretion of urinary Cu and Zn. ADDTC and EDDTC appear to be promising in the management of Pb poisoning. PMID- 2252550 TI - Influences of refined konjac meal on the levels of tissue lipids and the absorption of four minerals in rats. AB - This paper reports a study on the hypocholesterolemic effect of the refined konjac meal (RKM) containing about 80% glucomannan prepared from the tubers of Amorphophallus konjac K. Koch. Male and female Sprague-Dawley rats, 5 weeks old, were divided into five groups and fed a normal basal diet, a hypercholesterolemic diet (control diet), and three test diets (RKM added to the control diet at levels of 2.5, 5, and 10%, respectively) for 12 weeks. The results obtained indicate that RKM could markedly lower the cholesterol levels in the serum and the liver of rats eating hypercholesterolemic diets. At the end of the 4th week of feeding experiment, the serum cholesterol levels in the 5 and the 10% RKM groups and the liver cholesterol level in the 10% RKM group were significantly lower than those in the control groups. At the end of the 12th week, the serum cholesterol levels of all the three RKM groups were lowered to a normal level as was the liver cholesterol level of the 10% RKM group. The lipotropic effect of RKM was also confirmed by histopathologic examination of the livers. In addition to the hypocholesterolemic effects, RKM diets also increased stool bulk. Minor effects on the absorption and utilization of Ca, Fe, Zn, and Cu were found. PMID- 2252551 TI - Biochemical and immunochemical characterization of Caenorhabditis elegans metallothioneins I and II induced by cadmium. AB - Metallothioneins in Caenorhabditis elegans (CeMT-I and II) were purified by the combination of gel filtration, ion-exchange chromatography, and high-performance liquid chromatography. Amino acid compositions and amino-terminal sequences of CeMT-I and II were slightly different from those of vertebrate MTs previously reported, although cysteine residue contents were relatively high. Enzyme immunoassay using anti-CeMT-II antibody showed the difference of antigenicity to rat MT-I and II and even to CeMT-I. Immunohistochemical staining revealed the existence of CeMT-II in the intestine and the eggs, suggesting the role of MT in detoxification and homeostasis of heavy metals. PMID- 2252552 TI - A review of botulism in China. AB - The epidemiological characteristics and etiology of botulism in China, as well as the distribution of different types of Clostridium botulinum in China, are described. Through 1989, 15 provinces and autonomous regions reported the occurrence of botulism. There were 2861 cases involved in 745 outbreaks. Among the cases 421 died, with a case fatality of 14.7%. The main epidemiological characteristics of botulism in China are: (i) the major foods causing botulism are homemade fermented bean products which accounted for 62.6% of the cases; (ii) the incubation period is longer (3 h-54 days) than that described in the western literature (mostly 2-7 days); (iii) the peak occurrence is from February to May; (iv) the progression of symptoms and signs is slower than that of western cases. All types of C. botulinum, with the exception of type G, have been found in China. The distribution of various types of C. botulinum is significantly different between southern and northern China; this is related to the latitude and is correlated with the prevalence of this disease. Most of the botulism outbreaks occurred above 30 degrees north latitude in northern China and outbreaks rarely occurred below 30 degrees north latitude. Nationwide surveys showed that the average detection rate of C. botulinum spores in soil and foods in the northern parts of China was 14.8%, while it was only 2.5% in the south. C. botulinum types A, B, E, and F, which are involved in human botulism, were frequently found in the North, while types C and D, which are involved only in animal intoxication, were found more frequently in the south. PMID- 2252553 TI - Biological significance of [14C]phenol accumulation in different organs of a murrel, Channa punctatus, and the common carp, Cyprinus carpio. AB - Phenol, a ubiquitous component of industrial effluents, is a common pollutant of water resources and a serious threat to fish. The present work demonstrates that a significant amount of phenol is retained by various tissues of the common carp, Cyprinus carpio, and the snake-headed murrel, Channa punctatus. The rate of [14C]phenol accumulation was higher carp than in the murrel. It is suggested that retention of phenol in the brain and ovary may seriously affect the reproductive potential of the fish. PMID- 2252554 TI - Biochemical changes in rat lung during acute paraquat intoxication. AB - Paraquat (PQ) was administered intraperitoneally to male Wistar rats at a dose of 30 mg/kg. This dose caused mortality in 14% of the animals and significantly increased the lung wet weight by 28 and 93% at 2 and 3 days after treatment, respectively, compared to controls. The activity of several enzymes present in the lung was affected by PQ treatment. Pulmonary angiotensin-converting enzyme activity was significantly reduced at 4 h after PQ treatment and remained 32-36% below control levels during the following 3-day observation period. Alkaline phosphatase activity in the lung was significantly decreased by 26-33% at 1, 2, and 3 days after PQ treatment. Lung glucose-6-phosphate dehydrogenase activity demonstrated a drop at 4 h, recovery to control levels at 1 day, and a subsequent rise to levels 45-55% higher than control levels at 2 and 3 days. Glutathione reductase activity in the lung decreased significantly by 21% at 2 and 3 days. These changes in enzyme activities, which may reflect effects on different cell populations of the lung and process of damage and reparation, may prove to be useful as biochemical indicators of PQ toxicity. PMID- 2252555 TI - Microbiological analyses and inflammatory effects of settled dusts from rice and hay. AB - Fourteen samples of settled dust from two factories processing rice and wheat straw near Shanghai, China, were examined by dilution plating for total bacteria, gram-negative bacteria, thermophilic actinomycetes, and fungi. They were also examined for aflatoxin, endotoxin, and potential to stimulate production of human interleukin 1 beta (IL-1 beta) and to consume complement. The concentrations of total microorganisms were consistently greater than 10(7) CFU/g and ranged from 10(7) to 10(9) CFU/g. In general, the level of microbial contamination was greater in the hay dust samples than in the rice dust samples, with bacteria being the most numerous microorganisms observed followed by molds, thermophilic actinomycetes, and yeasts. The predominant fungi were species of Aspergillus, Cladosporium, Penicillium, Trichosporon, and Cryptococcus. No significant levels of aflatoxin were observed and the isolates of A. flavus examined lack significant aflatoxigenic potential. The levels of microorganisms in these samples, the types of organisms found, and the inflammatory mediators such as endotoxin suggest that workers exposed to these dusts may be at risk for respiratory illness. PMID- 2252556 TI - Safety evaluation of a potent tetanus vaccine (250 Lf) in guinea pigs (Cavia procellus). AB - A subacute toxicity study of a potent tetanus toxoid (250 Lf) was carried out in guinea pigs. The toxoid was injected subcutaneously at the nape of the neck at dose levels of 1.0, 1.5, and 2.0 ml in Groups II, III, and IV, respectively. In the controls (Group I) 2.0 ml of aluminum phosphate suspension was given in each injection. Periodic evaluations of body weight, food/water intake, general observable behavior, hematology, and blood chemistry in toxoid-injected guinea pigs were similar to those in control guinea pigs. Thus, the toxoid did not cause any side effects up to four times the dose proposed for humans. PMID- 2252557 TI - Bibliography of the current world literature. PMID- 2252558 TI - Organic mental disorders in HIV-1 infection. PMID- 2252559 TI - Genomic divergence of an HIV-2 from a German AIDS patient probably infected in Mali. AB - The complete nucleotide sequence of an HIV-2 isolate derived from a German AIDS patient with predominantly neurological symptoms is reported. The HIV-2BEN sequence is highly divergent from those of previously described HIV-2 and SIV strains. Evolutionary tree analysis of eight HIV-2 sequences reveals the existence of three HIV-2 groups. HIV-2BEN belongs to a group with two isolates from Ghana and The Gambia. Based on a comparison of HIV-2BEN with six HIV-2 isolates, SIVsmm and SIVmac, the variability of the structural env and gag proteins is similar within the HIV-2/SIVsmm/mac and HIV-1 groups. In contrast, the regulatory HIV-1 proteins are more highly conserved than those from HIV-2 strains. Multiple sequence alignments reveal that some domains of the envelope and regulatory proteins are well conserved among HIV-1, HIV-2/SIVsmm/mac, SIVagm and SIVmnd. The identification of conserved domains within the external glycoprotein could help to develop broadly active vaccines. PMID- 2252560 TI - Rapid and specific diagnosis of HIV-1 and HIV-2 infections: an evaluation of testing strategies. AB - To identify cost-effective testing strategies for HIV-1 and HIV-2 infections, we evaluated different combinations of tests on serum specimens from 1134 consecutive patients attending tuberculosis treatment centers in Abidjan, Cote d'lvoire. Virus-specific whole-virus enzyme-linked immunosorbent assay (WVE), Western blot (WB) and synthetic peptide enzyme-linked immunosorbent assay (SPE) were used in sequential fashion to determine the true prevalence of infection; 27% were reactive to HIV-1, 5% to HIV-2, and 10% to both viruses. Of 239 specimens positive on WB for both HIV-1 and HIV-2, SPE diagnosed 38% as HIV-1 reactive and 16% as HIV-2-reactive, while 46% remained reactive to both viruses. Using WVE or one of two rapid (5-10 min) mixed (HIV-1 and HIV-2) antigen tests (RMATs) as a screening test, followed by SPE as a supplemental test, gave results with sensitivity of 97.3-99.2%, specificity of 99.5-99.7%, and positive predictive value for diagnosing HIV infection of 99.4-99.6%, with important savings in time and reagent costs. SPE allows more specific distinction between HIV-1 and HIV-2 infections than WB, and could replace it as a supplemental test in many settings. WB may be required for specimens reactive on screening tests but negative on SPE, until sensitivity of the SPE is further evaluated. A mixed antigen screening test followed by SPE seems to be an efficient testing strategy for diagnosing HIV-1 and HIV-2 infections. PMID- 2252561 TI - An analysis of the economic impact of HIV infection among patients at Mama Yemo Hospital, Kinshasa, Zaire. AB - In a prospective study of adult admissions to the Department of Internal Medicine at Mama Yemo Hospital, Kinshasa, Zaire in late 1988, 129 women and 122 men were screened for HIV infection. Fifty per cent were found to be seropositive, with half of the seropositives meeting the World Health Organization (WHO) clinical AIDS definition. The HIV seropositives had a mortality rate of 50%, which was significantly higher (P = 0.004) than the 30% mortality rate seen in the seronegative group. Direct costs during hospitalization did not differ ($60.30 for HIV seropositives, $56.50 for HIV seronegatives), but pre-hospitalization expenses were significantly higher in the HIV-seropositive group ($170 for HIV seropositives, $110 for HIV seronegatives). Years of productive life lost due to death were also significantly higher for HIV seropositives versus HIV seronegatives (30.6 versus 21.3 years; P = 0.0007), and 73% of the premature mortality in the study population was attributable to HIV infection. PMID- 2252562 TI - Differences in knowledge of and risk factors for AIDS between Hispanic and non Hispanic women attending an urban family planning clinic. AB - Risk factors for AIDS, contraceptive use, seroprevalence of HIV, and level of knowledge before and after an AIDS education session were assessed for 657 clients attending a family planning clinic in Los Angeles, USA. History of a partner who was bisexual, an intravenous drug user, or a blood transfusion recipient were the most common risk factors. Spanish speakers reported fewer traditional risk factors than English speakers. They were also less likely to report a history of drug or alcohol use or sexually transmitted diseases, and to have had fewer sexual partners. Less than one-third of the women identified as being at risk of exposure were using condoms. None of 351 consecutive patients tested for HIV antibodies was positive. English speakers scored higher on both pre- and post-tests of knowledge about AIDS. Cultural factors may lower the personal risk of HIV exposure for Spanish-speaking women, but lack of knowledge about AIDS and partner behavior may increase risk. PMID- 2252563 TI - High HIV risk-taking among young gay men. AB - Previous research has shown younger age to be correlated with greater HIV sexual risk-taking among gay men. The purpose of this study was to identify variables associated with HIV risk-taking among younger gay men. Ninety-nine gay men aged 18-25 in three medium-sized West Coast communities completed self-report questionnaires regarding HIV-related behaviors and attitudes. Of the respondents, 43% reported having engaged in unprotected anal intercourse during the previous 6 months. Men who engaged in unprotected anal intercourse reported greater enjoyment of unprotected anal intercourse, perceived less risk of unprotected anal intercourse, labeled themselves as more at risk for AIDS, reported poorer communication skills with sexual partners, and were more likely to have a boyfriend/lover than men who had not engaged in high-risk sex. In addition, respondents perceived the likelihood of acquiring HIV from unprotected anal intercourse with young gay men to be significantly lower than with older gay men. These findings highlight the need for HIV risk-reduction interventions designed specifically for young gay men and identify critical areas to be targeted in such interventions. PMID- 2252564 TI - Prevention of perinatal HIV transmission: are there alternatives to pre-pregnancy serological screening in Kinshasa, Zaire? AB - Complete obstetrical and medical histories were obtained from 6312 women between the ages of 15 and 45 years who had undergone HIV serological tests. Individual factors were examined for sensitivity, specificity and positive predictive value of HIV infection. No individual risk factors for HIV infection were identified which had sensitivities greater than 60%. Combinations of factors were modelled by logistic regression. Only a model which included indicators of present illness with AIDS/HIV-related symptoms (i.e., chronic fever, diarrhea or profound weight loss) was predictive of HIV serostatus. These results suggest that identification of healthy women at high risk of HIV infection using non-serological information is not feasible. Thus, since the yearly cost of universal serological screening is prohibitively expensive in the Zairean context, HIV/AIDS education and prevention campaigns may in fact be a more cost-effective means of preventing perinatal transmission of HIV. PMID- 2252565 TI - Detection of HIV in fetal central nervous system tissue. AB - Neurological disease is a common finding in children with AIDS and in others without signs of disease but with evidence of congenital HIV-1 infection. To investigate the possibility that HIV-1 can infect fetal central nervous system (CNS) tissue and therefore possibly serve as the substrate for the abnormal neurodevelopment characteristic of pediatric AIDS, eight abortus CNS samples (one set of twins) from seven HIV-1-seropositive intravenous drug users (IVDUs) and eight control abortus CNS samples from eight HIV-1-seronegative IVDUs were analyzed for HIV-1 infection. HIV-1 nucleic acid was detected only after the use of polymerase chain reaction (PCR) in three of eight CNS samples from HIV seropositive IVDUs but not in samples from seronegative subjects. In situ hybridization confirmed that HIV-1 DNA sequences were in cells in the CNS parenchyma of two of the three positive samples. This study demonstrates that HIV 1 can infect human fetal CNS tissue in vivo, but that the use of PCR may be necessary for its detection. PMID- 2252567 TI - Chronic myeloid leukemia in a homosexual HIV-seropositive man. PMID- 2252566 TI - Two quick estimates of the HIV prevalence in homosexual men in Los Angeles, New York and San Francisco. The Multicenter AIDS Cohort Study. AB - Two rough methods are given to estimate the combined HIV prevalence in Los Angeles, New York and San Francisco in homosexual men. Both methods are related to the back calculation technique, and use AIDS surveillance data and information obtained from the Multicenter AIDS Cohort Study. Both methods suggest that the combined HIV prevalence is approximately 100,000, with a possible range of 80,000 140,000. PMID- 2252568 TI - Porphyria cutanea tarda associated with HIV infection. PMID- 2252569 TI - Porphyria cutanea tarda and HIV infection. PMID- 2252570 TI - Porphyria cutanea tarda associated with HIV infection: are those conditions pathogenetically related or merely coincidental? PMID- 2252571 TI - Correlation of HIV core antigen, antibody and immune complex levels in sera of HIV-infected individuals. PMID- 2252572 TI - Follow-up of HIV-1 seroconversion in a dialysed patient infected by an 'HIV negative' blood unit. PMID- 2252573 TI - Seropositivity for HTLV-1 among Italian prisoners. PMID- 2252574 TI - Heparine-like anticoagulant vasculitis associated with severe primary infection by HIV. PMID- 2252575 TI - Zidovudine and HIV-2 disease. PMID- 2252576 TI - World Health Organization consultation on the neuropsychiatric aspects of HIV-1 infection. Geneva, 11-13 January 1990. PMID- 2252577 TI - "Professional" and "nonprofessional" contractile cells in the lung. PMID- 2252579 TI - Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase. AB - Hydroxyl radical scavengers and xanthine oxidase inhibitors protect cultured bovine pulmonary endothelial cells (BPAEC) from lytic injury by the endotoxin lipopolysaccharide (LPS). We hypothesized that exposure of BPAEC to cytotoxic concentrations of LPS activated intracellular xanthine oxidase, and that intracellular iron-dependent hydroxyl radical formation (a Fenton reaction) ensued, resulting in cell lysis. To test this, the protective effects of deferoxamine against H2O2 and LPS-induced cytotoxicity to BPAEC was assessed by 51Cr release. Preincubation with 0.4 mM deferoxamine conferred 67 +/- 15% (mean +/- SE) protection from LPS-induced cytotoxicity but 48 h of preincubation were required to induce significant protection. Significant protection form a classical Fenton reaction model, injury by 50 microM H2O2, could be induced by a 1-h preincubation with a 0.4 mM deferoxamine. The dissociated time course suggested that deferoxamine might work by different mechanisms in these models. The effects of LPS and deferoxamine on BPAEC-associated xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity were assessed using a spectrofluorophotometric measurement of the conversion of pterin to isoxanthopterin. BPAEC had 106 +/- 7 microU/mg XD+XO activity; XO activity constituted 48 +/- 1% of total XO+XD activity. LPS at a cytotoxic concentration did not alter XO, XD, or percent XO. Deferoxamine had striking proportional inhibitory effects on XO and XD in intact cells. XO+XD activity fell to 6 +/- 1% of control levels during a 48-h exposure of BPAEC to deferoxamine. Deferoxamine did not inhibit XO+XD ex vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252578 TI - Smooth muscle cell markers in developing rat lung. AB - We employed a panel of antibodies directed against cytoskeletal and contractile proteins in a developmental study to follow the differentiation and distribution of smooth muscle-like cells in the rat lung. We observed that, in the mesenchyme around developing airways and vessels, desmin replaces vimentin as the predominant intermediate filament as specialization toward smooth muscle occurs. Normally, desmin and smooth muscle myosin were expressed together in the cells and their acquisition appeared indicative of terminal differentiation of smooth muscle. In this regard, the maturation of vascular smooth muscle is delayed in the lung relative to that surrounding the developing air passages. alpha-smooth muscle actin-containing cells form a thicker coat around the primitive airway tubes and extend farther down the tree than desmin or smooth muscle myosin positive cells. This suggests that the alpha-actin is a marker for initial differentiation of smooth muscle cells and that these cells arise from the enveloping mesenchyme. In the pseudoglandular and canalicular lung, alpha-actin containing cells were also found in regions of epithelial tube cleft formation, suggesting an association with the process of branching morphogenesis. In addition, a large complement of alpha-actin-positive but smooth muscle myosin negative cells were observed in the saccular interstitium during the period of secondary saccule formation and capillary reorganization that leads to final alveolarization. In summary, we note an association of smooth muscle-like, alpha actin-containing cells with areas and periods of remodeling during normal pulmonary development. This observation may have relevance to the repair process in the adult lung. PMID- 2252580 TI - Cytolytic human lung lymphocytes: characterization of intragranular protease content and response to interleukin-2. AB - Cytolytic lymphocytes play an important role in defense against viral and neoplastic disease. Integral to the function of these cells is the content of lysosomal granules. Recent attention has focused on a family of proteases present in the granules of natural killer (NK) cells, interleukin-2 (IL-2)-activated NK cells (LAK cells), and cytotoxic T lymphocytes (CTL). In the current investigation, lymphocytes were obtained from human lung parenchyma and peripheral blood. Following activation with IL-2, both groups of lymphocytes exhibited comparable cytolytic activity against K562 targets. Lysosomal granules obtained from these cells contained two serine proteases with molecular weights of 30 and 28 kD. These proteases were capable of hydrolyzing benzyloxycarbonyl-L lysine thiobenzyl ester (BLT-ester), a substrate of cytolytic lymphocyte proteases. When compared to blood, unactivated lung lymphocytes contained significantly higher levels of protease content. Although IL-2 produced a significant increase in blood lymphocyte protease content, no change in lung lymphocyte granule protease activity was observed. We conclude that cytolytic lung lymphocytes contain high levels of lysosomal granule protease but differ from blood lymphocytes in the ability to increase protease content following activation with IL-2. The high level of protease content in cytolytic lung lymphocytes suggests that these cells could produce local tissue injury during the release of lysosomal granules. PMID- 2252581 TI - Separation of bovine bronchial epithelial cell subpopulations by density centrifugation: a method to isolate ciliated and nonciliated cell fractions. AB - Bronchial epithelial cells isolated by protease digestion can be cultured in vitro for the study of proliferation and differentiation. However, these cells represent a heterogenous population, the components of which likely interact with one another. We attempted to utilize density gradient centrifugation as a method to prepare subpopulations of these bronchial epithelial cells. The suspension of the cells obtained by protease digestion of the bovine bronchi was mixed with an equal volume of colloidal silica reagent, Sepracell-MN, and centrifuged to form a continuous density gradient. Two distinct cell layers were identified in addition to a cell pellet at the bottom. Cells from fraction A (top layer) were more than 95% ciliated cells by morphologic examination. These ciliated cells were recovered intact as assessed by trypan blue dye exclusion and by watching beating of their cilia. The cells from fraction C (bottom layer) were 89.9 +/- 3.88% nonciliated, small round cells with a densely staining nucleus and scant cytoplasm. Comparison of cell morphology of these cells with basal cells in vivo and electron microscopic examinations suggested that these cells were basal cells. These basal cells showed an exponential cell proliferation until confluence in Ham's F12 with supplements, LHC9, and a 1:1 mixture of Medium-199 and modified Eagle's medium with 2% fetal calf serum. In contrast, the cells from fraction A grew minimally in all conditions tested. This difference was also shown in the study of DNA synthesis by [3H]thymidine uptake. Enzyme-linked immunosorbent assay for release of bovine fibronectin into cultured media indicated that fraction C cells secreted much more fibronectin (532 +/- 5.28 ng/10(6) cells/h) than fraction A cells (73.4 +/- 1.00). We also used Percoll as a density-gradient reagent and showed potential usefulness in the preparation of cell fractions of bronchial epithelial cells. In conclusion, it was possible to separate ciliated and nonciliated, presumably basal, cells of bovine bronchial epithelial cells. These differed in growth and fibronectin secretion. Studies of airway cell biology may be aided by the availability of more homogenous cell populations. PMID- 2252582 TI - Fibronectin is not detectable on the intact buccal epithelial surface of normal rats or humans. AB - Fibronectin (FN) has been postulated to prevent gram-negative bacillary (GNB) colonization of the oropharynx by covering epithelial cell GNB receptors. We investigated the distribution of FN along the luminal surface of oropharyngeal epithelium in animals and humans. Examination of buccal epithelial biopsies obtained from normal rats revealed no luminal surface FN by either immunofluorescent or immunoperoxidase staining. Extraction of epithelial surface proteins and quantitation of FN by rocket immunoelectrophoresis and electrophoretic transfer to nitrocellulose followed by immunologic detection also detected no FN from normal animals' oropharyngeal biopsies. Buccal epithelial biopsies from three normal humans were examined for FN using electrophoretic transfer to nitrocellulose followed by immunologic detection, and no FN was demonstrable. Our results suggest that FN is not present on the oral epithelial surface of healthy rodents or humans, and that FN may not be involved in the pathogenesis of bacillary colonization. PMID- 2252583 TI - Human alveolar type II cells: stimulation of DNA synthesis by insulin and endothelial cell growth supplement. AB - Proliferation of type II cells is important for the recovery of the alveolar epithelium after acute lung injury. However, the factors that regulate the proliferation of human type II cells are unknown. Human alveolar type II cells were isolated from resected lung by dissociation with porcine pancreatic elastase and crystalline trypsin and purified by density-gradient centrifugation and serial differential adherence. The purity of the type II cells in the final adherent preparation was 84.4 +/- 1.1% type II cells by alkaline phosphatase and 87.7 +/- 2.8% by cytokeratin (n = 7). The medium MCDB-151 with 0.4% fetal bovine serum (FBS) was used to demonstrate the stimulatory effect of individual growth factors. Under these conditions, thymidine incorporation was stimulated by insulin, epidermal growth factor, endothelial cell growth supplement (ECGS), and acidic and basic fibroblast growth factors. Cholera toxin did not stimulate thymidine incorporation. The most effective stimulation was by the combination of insulin and ECGS. The incorporation of bromodeoxyuridine was used to identify the proportion of cells that were active in DNA synthesis. Insulin and ECGS increased the percentage of cells that incorporated bromodeoxyuridine from 8.5 +/- 1.3% to 21.3 +/- 2.4% (n = 6). Mitotic figures were seen in smears prepared from cultures incubated with insulin and ECGS. This observation was confirmed by electron microscopy, which demonstrated type II cells in metaphase. Increasing the concentration of FBS or human serum in the culture medium to 10% decreased the stimulatory effect of insulin and ECGS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252584 TI - Histamine acting on a histamine type 1 (H1) receptor increases beta-glucuronidase release from human lung macrophages. AB - The effects of histamine on lung macrophages have been studied by both biologic and radioligand experiments. After overnight adherence, lung macrophages spontaneously released beta-glucuronidase (beta-G) at a rate of approximately 7 nmol of hydrolyzed substrate/h/million cells. Histamine at low concentrations (10(-9) to 10(-8) M) resulted in a consistent potentiation of this release. The concentration-effect curve of histamine was bell-shaped, reaching an optimum at 10(-9) M, with concentrations greater than 10(-8) M having no significant effect. At a maximally effective concentration (10(-9) M), histamine evoked a 135 +/- 9.6% (mean +/- SE; n = 8, P less than 0.001) potentiation in the total amount of beta-G released during the first 60 min of incubation. This increase in beta-G release represented both a slight increase in beta-G synthesis as well as an increase in the percentage of beta-G released. When the secreted beta-G is expressed as a percentage of total content, histamine (10(-9) M) evoked a 125 +/- 3.2% (mean +/- SE; n = 27, P less than 0.0005) enhancement. The potentiation of beta-G release by histamine was evident after 45 min of incubation and persisted for up to 6 h. The potentiation of beta-G by histamine was sensitive to inhibition by pyrilamine (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252586 TI - Protein targeting signals. PMID- 2252585 TI - Immunohistochemical localization of endopeptidase 24.15 in rat trachea, lung tissue, and alveolar macrophages. AB - Endopeptidase 24.15 (EP 24.15; EC 3.4.24.15), a zinc-metalloendopeptidase purified from rat brain and testes and also present in many other tissues, including the lung, degrades substance P, neurotensin, bradykinin, luteinizing hormone-releasing hormone, and some other bioactive peptides. The enzyme, present both as soluble cytoplasmic and membrane-bound forms, also rapidly converts dynorphin, alpha- and beta-neoendorphin, and some other opioid peptides into their respective enkephalins. In this study, a rabbit antibody to EP 24.15 purified from rat testes was used to study distribution of the enzyme in rat trachea, lung tissue, and alveolar macrophages (AMs) by immunohistochemical techniques. We found intense immunoreactivity to EP 24.15 within the cytoplasm of ciliated epithelial cells of tracheobronchial mucosa extending from trachea to terminal bronchioles. In addition, large myelinated paratracheal and peribronchial nerve fibers showed immunoreactivity. Blood vessels and alveolar lining cells were negative. AMs also showed intense diffuse cytoplasmic immunoreactivity. The findings of EP 24.15 immunoreactivity in airway epithelium, AMs, and paratracheal and peribroncheal nerve fibers suggest that the enzyme may modulate the activities of bioactive peptides within the lung. PMID- 2252587 TI - Translocation of proteins with signal sequences across membranes. PMID- 2252588 TI - Membrane translocation of proteins without hydrophobic signal peptides. PMID- 2252589 TI - Regulated secretion. PMID- 2252590 TI - A new hematopoietic growth factor receptor superfamily: structural features and implications for signal transduction. PMID- 2252591 TI - Lipid traffic in eukaryotic cells: mechanisms for intracellular transport and organelle-specific enrichment of lipids. PMID- 2252592 TI - Endomembrane traffic and targeting in plant cells. PMID- 2252593 TI - Membrane protein structure. PMID- 2252595 TI - Membranes. PMID- 2252594 TI - Uniporters and anion antiporters. PMID- 2252596 TI - [Generalized genetic parameters of multiple traits]. AB - Generalized phenotypic variance (p), genetic variance (g), heritability (h2) and genetic correlation coefficient (p) are defined as follows. (formula, see text) The profile analysis of variation, covariation of multiple traits and correlation between trait sets can be made by using the parameters above. Two examples about cotton and alfalfa are given to explain these new parameters' estimation and application. PMID- 2252597 TI - [Studies on the systematic status of a new species of Drosophila (sophophora)- from morphological to molecular level]. AB - Bock and Wheeler (1972) reviewed the Drosophila melanogaster species group in which more than 70 species were classified into a number of subgroups. One of them is the takahashii species subgroup which is a large subgroup with 12 species. We collected many specimens of drosophilid fly in Mt. Huaping, Guangxi Province and Mt. Siming, Zhejiang Province in 1983, among which taxon A and taxon B were thought to be a new species, belonging to the takahashii subgroup and named as D. liui sp. n. However, after Prof. T. Okada examined this new species, he thought it is the same as the known species D. nepalensis Okada, 1955 from Nepal and later Dr. J. Toda examined the same species and thought it was the known species D. prostipennis Lin, in Bock and Wheeler 1972 from Taiwan and/or D. trilutea Bock and Wheeler 1972 from Borneo, so that D. liui sp. n. is considered as the species incertae sedis. In the present paper, we studied 6 species of this subgroup: D. takahashii, D. lutescens, D. liui sp. n., D. nepalensis, D. prostipennis and D. trilutea. Our studies from morphological to molecular level provided the evidences which can support the description of a new species, hence we draw the conclusion that D. liui sp. n. is a new member of the takahashii subgroup. PMID- 2252598 TI - [Study on antifreeze protein in fishes. II. The cloning of antifreeze protein gene cDNA of Pseudopleuronectes yokohamae and its expression in E. coli]. AB - Pseudopleuronectes yokohamae, existing in the Yellow Sea of China, contains antifreeze peptide (AFP). This protein could depress the serum freezing point. On the basis of purification and characterization of this protein, we synthesized a segment of Oligo-nucleotides of antifreeze protein gene as a primer and hybridized with the mRNA of Pseudopleuronectes yokohamae. The cDNA of antifreeze protein gene has specifically been reversely transcribed. This segment has been cloned onto pUC19 with Ecor I linker method. After confirmation of the insert segment of the cDNA of antifreeze protein gene, the zymogram was detected and the sequence of the nucleotides was determined. This recombinated clone was transformed into E. coli JM83 and expressed well. PMID- 2252599 TI - [A novel type of phase variation regarding integrated and free states of plasmid pFDX163 in Bacillus stearothermophilus CU21]. AB - pFDX1 is a recombinant plasmid which carries a foreign gene xylE. By selecting for kanamycin-resistant mutants of Bacillus stearothermophilus CU21(pFDX1) at higher temperature, a variant strain CU21-163 was obtained. This strain harbors a mutant plasmid pFDX163, which was formed by insertion of a 2.0kb H-fragment from the CU21 genome onto the plasmid pFDX1. pFDX163 was supposed to be integrated into the CU21 chromosome via homologous recombination of H-fragments. The CU21 163 strain consists of two cell types, i.e. y-cell and w-cell. The expression level of xylE gene in the former is higher than that in the latter. The progeny of a y-cell always contains some w-cells, while that of a w-cell contains y cells. This is supposed to be due to a phase variation of CU21-163. Analysis on the amount of free and integrated plasmid DNA in different DNA samples of CU21 163 cells allows us to draw the conclusion that there are both free and integrated plasmids in the y-cells, whereas only integrated ones in the w-cells. PMID- 2252600 TI - [Preparation of human minisatellite DNA probes]. AB - A 23-mer oligonucleotide based on the core sequence was chemically synthesized and used to screen the human genomic library. Fifteen positive recombinants containing the minisatellite sequences were identified, and one of them, C35.9, was used to perform Southern hybridization with the DNAs from unrelated Chinese individuals. Each sample has 3-11 hybridizing bands, and some of which are polymorphic. The band patterns detected under controlled condition are individual specific in a limited population. This indicates that the minisatellites obtained by screening the library can be used to detect the polymorphisms of the minisatellites. PMID- 2252601 TI - [The diagnosable rate of beta-thalassemia in Chinese population and the strategy for selecting genetic markers in prenatal diagnosis of the disease]. AB - It is possible to use some beta-thalassemia gene linkage markers for prenatal diagnosis of the disease currently. But there are some limitations due to incomplete linkage between these genetic markers and beta-thalassemia gene in population. The diagnosable rate of the genetic markers and their combinations have been calculated according to the polymorphism distribution data of the seven genetic markers in Chinese population. Then according to the diagnosable rate of each genetic marker and their combinations, the following is deduced: (1) Precedent estimation to the diagnosable rate of prenatal diagnosis; (2) Select the optimum strategy for prenatal diagnosis of beta-thalassemia suitable for Chinese population. In this paper, an optimum line is presented, regarding to select genetic markers for prenatal diagnosis of beta-thalassemia in Chinese population. Meanwhile, the method of gene linkage analysis and that of using oligonucleotide probe are compared. PMID- 2252602 TI - [Assessment of the mutagenic effect of maternal factors on human chorionic villi by micronucleus test]. AB - Rapid determination of DNA damage by micronucleus test is well accepted. Animal bone marrow cells or human peripheral lymphocytes used in most studies could not directly reflect the influence of the mutagenic effect on the offsprings by environmental factors. Human chorionic villi micronucleus test to detect directly the mutagenic effect of environmental factors has not been reported in the literature. Direct determination of human chorionic villi micronuclei (CVMN) was established in our laboratory, to study the mutagenic effect of mother's age, gravidity, gestation age, abortion history, contraception (condom, diaphragm, rhythm, oral contraceptives, spermicide or IUD), smoking and drinking on the offsprings. Cross investigation and micronucleus test were used in 507 couples undergoing artificial abortion. Micronuclei were scored according to Countryman's standard 2,000 interphases were observed in each subject for CVMN frequency (%). Arcsine transformation (arcsine [Sqr (P)]) was used in transforming CVMN frequency and the analysis of variance were used for statistics. No correlation between CVMN frequency and mother's age, gravidity, gestation age, abortion history, and contraception was found. Neither smoking nor drinking habit was found among the women of this study. The CVMN frequency of husband smoking was 0.7645 +/- 0.0561%, of husband non-smoking-drinking was 0.5522 +/- 0.0616%, of husband drinking was 0.5667 +/- 0.2004%, of husband smoking and drinking was 0.7944 +/- 0.0754%. There was a statistical difference in CVMN frequency between husband smoking and non-smoking (F = 2.78 DF = 408 P less than 0.05). No significant difference was found between husband drinking and non-drinking. PMID- 2252603 TI - [Studies on polymorphism of C6 in Han nationality of China]. AB - The polymorphism of C6 in three groups of Han nationality was investigated by using polyacrylamide gel isoelectric focusing and immunoblotting technique. The gene frequencies obtained are as follows: Zhangzhou City (Fujiang Province) C6*A:0.4634, C6*B:0.5000, C6*R:0.0366 (C6*B2:0.0317); Chendu City (Sichuan Province) C6*A:0.4975, C6*B:0.4480, C6*R:0.0545 (C6*B2:0.0396); Harbin City (Heilongjiang Province) C6*A:0.4708, C6*B:0.5219, C6*R:0.0073 (C6*B2:0.0073). The frequency of C6*A in Mongoloid populations is usually lower than 0.5, while that of black people ranges between 0.5 and 0.6 and that of white people is higher than 0.6. The other difference between Caucasian and Mongoloid is that the former has very few C6*B2 while the frequency of C6*B2 in the latter ranges from 0.03 to 0.07. PMID- 2252604 TI - Carbon-13 NMR imaging study of in-vivo glucose metabolism. AB - Carbon-13 NMR spectroscopy and chemical shift selective imaging studies of in vivo glucose metabolism were performed at 2.0 T. Some metabolite peaks were observed in 13C NMR spectra, and carbon NMR imaging focused in the spectral region attributed to D-1-13C-glucose were also performed. A 13C NMR signal accumulated in the liver was detected and the average time resolution of these spectra and images were 10 and 30 minutes, respectively. PMID- 2252605 TI - Direct stereotactic intracerebral injection of monoclonal antibodies and their fragments: a potential approach to brain tumor immunotherapy. AB - Delivery of monoclonal antibodies (Mab) to brain tumors is restricted by the blood:brain barrier. To circumvent this problem, we studied direct stereotactic injection of the Mab into the brain. An anti-melanoma intact Mab and its Fab fragments, which do not react with normal rat brain, were radioiodinated and injected either intracerebrally (IC) or intravenously (IV) into rats. At 5 days after injection, IC delivery of intact antibody was 101 times higher than IV delivery. The ratio of radioantibody in injected cerebrum:blood was 14:1. With IC delivered Fab fragments, the radioantibody ratio in injected cerebrum:blood was 242:1 at 5 days after IC injection, with a 680-fold delivery advantage over IV injection. These data demonstrate a dramatic regional delivery advantage for intact Mab and especially for Fab fragments injected directly into the brain. This route of Mab delivery may have therapeutic potential for brain tumors. PMID- 2252607 TI - Investigation by scintigraphic methods of platelet kinetics under normal and septic shock conditions in the experimental baboon model. AB - This study concerned the correlation of platelet kinetics with the pathogenic course of septic shock and adult respiratory distress syndrome (ARDS) in the anesthetised baboon model. 111In-tropolonate platelets were traced in vivo in normal baboons (n = 7) and in Escherichia coli-infected baboons, which were reinjected with the labeled autologous platelets either 2 hr after the onset of the E. coli infusion (procedure A: n = 4) or simultaneously with the infusion (procedure B; n = 3). One minute images were taken hourly for 5 hr, using a gamma camera and data processor. Time-activity curves were obtained for platelet clearance from the blood and the lungs and for platelet accumulation in the liver and spleen. A significant retention of platelets in the lungs of baboons with E. coli-induced septic shock was noted, as well as an accelerated clearance from the circulation. Platelets were distributed mainly to the spleen after induction of bacteremia, later substantially moved to the liver, and even later moved back to the spleen. PMID- 2252606 TI - Subcortical arteriosclerotic encephalopathy: single photon emission computed tomography-magnetic resonance imaging correlation. AB - Regional cerebral blood flow was studied using 99mTc-HM-PAO and single photon emission computed tomography (SPECT) in five healthy subjects and in eight patients with clinical and computed tomography (CT) features of subcortical arteriosclerotic encephalopathy. All the patients and controls underwent magnetic resonance imaging (MRI). Circumscribed cortical hypoperfusion was observed in three patients, and in one case there was no evidence of cortical or sulcal alterations on MRI. In all the patients, a reduction of the white matter perfusion was found in periventricular and/or supraventricular regions. This pattern was substantially correlated with the typical white matter hyperintensities shown by MRI scans. These findings support the hypothesis that white matter hypoperfusion is the most prominent functional abnormality in subcortical arteriosclerotic encephalopathy. PMID- 2252608 TI - Thrombogenicity and long-term patency in autologous vein, polytetrafluoroethylene (PTFE) and silk grafts in a sheep model: evaluated through the use of indium-III labeled platelets. AB - Vascular conduits have different thrombogenicity and since platelet sequestration onto a graft surface is a contributing factor for subsequent graft occlusion, this constitutes an important feature. Most studies on thrombogenicity have been done as short-term experiments. In the present communication we have evaluated graft thrombogenicity for autologous vein, polytetrafluoroethylene (PTFE), and pure chinese silk grafts, immediately after graft implantation, 1, and 2 months thereafter, using Indium-111-labelled platelets, evaluated platelet consumption, and studied patency up to 4 months after graft implantation in a sheep model. The least thrombogenic graft material was found to be the autologous vein, followed by the silk graft and the PTFE graft. Already 1 month after graft implantation healing of the grafts seems to have occurred, resulting in a minimal detectable platelet sequestration. Platelet consumption by the graft can be seen as a decrease in platelet count in the peripheral blood. Four months after graft implantation the autologous vein grafts showed a patency rate of 71%, the silk grafts 55%, and the PTFE grafts 38%. The pure silk prosthesis revealed though at harvest of the grafts, a high incidence of aneurysmal graft dilatation. PMID- 2252609 TI - Continuous arterial positron monitor for quantitation in PET imaging. AB - Quantitative measures of physiologic function with PET require continuous monitoring of arterial positron isotope concentration. A device has been developed that automates this process. This device has advantages over manual sampling techniques with syringes since fewer personnel are required, measurements are less error prone, and more continuous measures of arterial positron concentration are available. A constant flow infusion/withdrawal pump withdraws blood from the radial artery through a catheter connected to 0.5 mm inner diameter teflon tubing. This tubing is wrapped around a 50 mm thick by 50 mm diameter NaI(T1) crystal that is interfaced to a photomultiplier tube (PMT) and encased in a cylindrical lead shield. This crystal detects 511 Kev photons that result from positron annihilation. The device sensitivity is greater than 240 (cts/sec)/(microCi/ml) corresponding to a peak activity of approximately 10,000 cts/sec for a 50 mCi bolus injection in an adult. The system dynamic response has been measured and the true arterial input function is recovered by deconvolution. The system has been used clinically for more than 400 human PET studies and has been a reliable continuous monitor of arterial positron concentration. PMID- 2252610 TI - Current status of imaging in the diagnosis of acute appendicitis. AB - The diagnosis of acute appendicitis remains a problem in clinical surgery. Negative appendectomy represents misdiagnosis, and perforation may be the result of delayed diagnosis. The accuracy of diagnosis has improved little in decades, with a rate of 20% for negative appendectomy and 21% for perforation in one large series [Lewis FR: Arch Surg 110:677-685, 1975. Clearly, the need exists for a sensitive yet specific diagnostic imaging tool. The purpose of this paper is to review the role of currently available imaging modalities in the diagnosis of acute appendicitis. PMID- 2252611 TI - Sialyltransferase activity in AF10 myeloma cell line. AB - A STA was observed in a human-derived myeloma cell line, AF10, that produces IgE paraprotein. The STA in the culture medium of the AF10 myeloma cell line was associated in the 24 to 48 hr period of incubation with IgE biosynthesis, and increased thereafter up to 72 hr, while IgE remained stable. These data support our previous observations that human myeloma cells are associated with a relatively high production of sialyltransferase, which is released to the medium, presumably by a mechanism of shedding. PMID- 2252612 TI - 26-hydroxycholesterol-stimulated DNA synthesis in smooth muscle cells and induction of endothelial injury using a coculture technique. AB - We investigated the effects of 0.5, 2.5, and 10 micrograms/ml of cholesterol or 26-hydroxycholesterol on bovine aortic ECs and SMCs. Suppression of viable cell density and cytotoxic changes in both cells were induced by 2.5 and 10 micrograms/ml 26-hydroxycholesterol. ECs were more severely damaged than SMCs in the presence of 26-hydroxycholesterol. Levels of up to 10 micrograms/ml cholesterol had no effect on ECs or SMCs growth or cytotoxicity. Confluent ECs exposed to 2.5 or 10 micrograms/ml of 26-hydroxycholesterol secreted significant amounts of 6-ketoprostaglandin F1 alpha after a 24-hr incubation. An equivalent concentration of cholesterol had no such effect. SMCs cocultured with ECs exposed to 10 micrograms/ml 26-hydroxycholesterol, when compared with an equivalent level of cholesterol, synthesized DNA in significantly greater amounts during a 24-hr incubation. The cocultured ECs incubated in the presence of 2.5 and 10 micrograms/ml 26-hydroxycholesterol were partially detached due to cell death. However, no difference was observed in the DNA content of SMCs cultured without ECs in the presence of cholesterol or 26-hydroxycholesterol. The results suggest that 26-hydroxycholesterol produced not only cytotoxicity to ECs and SMCs but also stimulated DNA synthesis in SMCs through endothelial injury. PMID- 2252613 TI - Propranolol-sensitive and phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets from rat adipocytes. AB - Norepinephrine, epinephrine, and isoproterenol at concentrations of 5.5 x 10(-8) M were found to elicit lipolysis in a cell-free system containing lipid droplets from fat cells and lipase solution. In the cell-free system, the beta-blockers propranolol and dichloroisoproterenol at concentrations of 1 microM inhibited lipolysis induced by norepinephrine, whereas similar concentrations of the alpha blockers phenoxybenzamine and yohimbine did not inhibit lipolysis. The binding of norepinephrine to endogenous lipid droplets was inhibited by propranolol, but not by phenoxybenzamine. We concluded that the propranolol-sensitive, phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets is involved in lipolysis in fat cells. Treatment of endogenous lipid droplets with phospholipase C, but not phospholipase D, trypsin, chymotrypsin, or neuraminidase, inhibited the propranolol-sensitive binding of norepinephrine to the droplets. These results suggest that the phosphate group of phospholipid in endogenous lipid droplets may be the site of propranolol-sensitive binding of norepinephrine. The physiological significance of the propranolol-sensitive binding is discussed. PMID- 2252614 TI - The relation of diabetic control to in vivo pH of soft tissue abscesses. AB - It has been shown that induced soft tissue abscesses have a lower intra-abscess pH in the uncontrolled diabetic host than in the nondiabetic control. These differences were felt to be secondary to alterations in white cell metabolism. The current study compares the intra-abscess pH in three groups of mice: (I) nondiabetic, (II) untreated diabetic, and (III) insulin-treated diabetic. Diabetes was induced with streptozotocin in male white mice. The bacteria used to induce the abscesses were a combination of B. fragilis and Enterococcus. The blood glucose values of groups I, II, and III were 189 mg% (+/- 20.3), 256 mg% (+/- 121.9), and 712.8 mg% (+/- 169.7), respectively. None of the animals were ketotic, and peritoneal pH (reflecting systemic pH) showed no significant differences between groups. There were no significant differences in colony counts between any groups. The intra-abscess pH values of groups I, II, and III were 6.97 (+/- 0.26), 6.85 (+/- 0.41), and 6.08 (+/- 0.70). The differences in intra-abscess pH and blood glucose levels were all significantly different from each other when all three groups were compared. The insulin-treated mice tended to return to normality but had the widest spread of values. Since a decrease in intra-abscess pH has been felt to be a reflection of white cell activity, our studies may be the first to demonstrate an in vivo effect of insulin on white cell activity. PMID- 2252615 TI - Resolution and kinetic characterization of glutathione S-transferases from human jejunal mucosa. AB - Cytosolic glutathione S-transferases were purified from human jejunal mucosa by affinity chromatography on S-hexylglutathione-Sepharose 4B. Chromatofocusing in the pH range 7-4 yielded peaks with apparent pI's of 7.2 (peak 1), 5.2 (peak 2), and 4.4 (peak 3). Each enzymatic fraction was shown to have a homodimeric structure, with subunit mass of 24.9 +/- 0.5 (P1), 27.9 +/- 0.9 (P2), and 23.4 +/ 0.8 (P3) kDa, as determined by SDS-PAGE. The substrate specificity of each peak was tested using discriminating substrates for basic, near-neutral, and acidic GSTs. With cumene hydroperoxide, the diagnostic substrate for the alpha (basic) class of GSTs, P1 showed 8- to 36-fold higher activity than P2 and P3. Ethacrynic acid, the selective substrate for the acidic enzyme (pi), gave highest activity with P3. The inhibitory potentials of sulfobromophthalein, cibacron blue, tributyltin acetate, triphenyltin chloride, and bromphenol blue were also tested. A qualitative resemblance between P1 and alpha, and P3 and pi GSTs was noted. The substrate specificity and inhibiton parameters of P2 corresponded most closely to those of mu-GST. The relative abundances of P1, P2, and P3 (based on CDNB conjugating activity) were 35, 5, and 60%, respectively. PMID- 2252616 TI - Effect of trifluoperazine on cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro. AB - We recently demonstrated that the preventive effect of trifluoperazine (a potent inhibitor of calmodulin, protein kinase C, and phospholipase A2) on cholesterol induced atherogenic activity of smooth muscle cells was mediated through its ability to inhibit smooth muscle cellular DNA synthesis coupled with stimulation of LDL receptor synthesis. The present study addressed the effect of trifluoperazine on cholesterol metabolism of aortic SMCs enriched with cholesterol through the nonreceptor pathway and revealed that (a) TFP caused inhibition of cholesterol synthesis compared with control cells bathed with hypercholesterolemic medium alone. (b) The drug also caused inhibition of free cholesterol and cholesteryl ester accumulation within smooth muscle cells compared to control cells. These results demonstrate that the preventive effect of TFP on atherogenic activity of smooth muscle cells may also be due to its ability to affect the altered/modified cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro. PMID- 2252618 TI - Accelerated heme synthesis and degradation in transformed fibroblasts. AB - Various parameters of the heme biosynthetic pathway were studied in two cell lines, one nontransformed and the other malignantly transformed (MLV/MS), both replicating at the same rate. Using the above system enabled us to distinguish between phenomena characteristic of the malignant transformation per se and those due to accelerated growth rate. Heme synthesis and degradation as well as the activities of ALAS, ALAD, PBGD, and FC were found to be increased in the transformed cells. However, the concentration of intracellular heme was markedly reduced from 30.4 +/- 4.4 pmole/mg protein in nontransformed cells to 10.5 +/- 2.6 pmole/mg protein in transformed cells. These observations show that malignant transformation leads to changes in heme metabolism unrelated to growth rate in this cell line. PMID- 2252617 TI - Effects of a first exposure to ethanol on the compositions of neutral and polar lipids in Euglena gracilis Z, taken as a hepatic cell model: equilibration by citrulline-malate. AB - In comparison to the lipid composition of Euglena cells fed with lactate, a first exposure of the cells to ethanol favors the production of neutral lipids containing mainly unsaturated fatty acids. The ethanol diminishes drastically the proportion of PC and weakly that of PE. In contrast, it increases slightly the proportion of DPG. The ethanol induces important changes in the fatty acid distributions of each lipid class, suggesting modifications of the elongation desaturation system. On the one hand the proportion of unsaturated fatty acids is increased and, on the other hand, the last double bond is predominantly situated in the delta 6 position in place of delta 3. The addition of the complex citrulline-malate corrects most of these changes. PMID- 2252619 TI - Modulation of Masheri- and benzo[a]pyrene-inducible carcinogen-metabolizing enzymes by dietary vitamin A. AB - The modulatory role of dietary vitamin A on the carcinogen metabolizing enzymes was studied in masheri extract and benzo[a]pyrene-treated rats. Weanling male Sprague-Dawley rats were fed vitamin A deficient (SR-) and vitamin A sufficient (SR+) semisynthetic diets for 12 weeks. ME/B[a]P treatment significantly increased the phase I activating enzymes in both SR- and SR+ groups. However, a higher percentage increase in enzyme activities was observed in both liver and lung of the SR- animals compared to the SR+ groups. Glutathione content and activity of glutathione S-transferase were decreased in both liver and lung of SR animals on treatment with either ME or B[a]P. In the SR+ group, an increase in GSH content and GST activity was observed following the ME/B[a]P treatment. The hepatic pool of vitamin A was depleted while that of vitamin C was increased after ME or B[a]P treatment in both SR- and SR+ groups. PMID- 2252620 TI - Cerebrospinal fluid concentrations of S-adenosylmethionine, methionine, and 5 methyltetrahydrofolate in a reference population: cerebrospinal fluid S adenosylmethionine declines with age in humans. AB - Cerebrospinal fluid concentrations of S-adenosylmethionine, methionine, and 5 methyltetrahydrofolate were measured in 80 children and young adults in whom there was no disturbance of the methyl transfer pathway. Cerebrospinal fluid was collected under standardized conditions and analyzed by high-performance liquid chromatography. S-Adenosylmethionine, but not methionine nor 5 methyltetrahydrofolate, concentrations declined sharply during the first year of life. There was no correlation between concentrations of S-adenosylmethionine and methionine or 5-methyltetrahydrofolate. Reference ranges for the three metabolites are given. PMID- 2252621 TI - Concentrations of neopterin and biopterin in the cerebrospinal fluid of patients with Parkinson's disease. AB - The concentrations of neopterin and biopterin in CSF of 18 younger and 10 older, control patients and of 18 patients with Parkinson's disease were measured by high-performance liquid chromatography with fluorescence detection. Both neopterin concentrations and the neopterin to biopterin ratios in CSF were lower in 50-year or younger group than in 51-year or older group. Biopterin concentrations were also decreased but not significantly in the older group. The concentrations of neopterin and biopterin in CSF of patients with Parkinson's disease were lower than those of the age-matched older control group. However, the neopterin/biopterin ratios tended to be lower but not change significantly as compared to the age-matched older control group. PMID- 2252622 TI - The lymphatics and lymphoreticular tissues in relation to the action of sex hormones. PMID- 2252623 TI - Mechanisms causing initial lymphatics to expand and compress to promote lymph flow. AB - Microlymphatics can be devided into two segments, initial lymphatics which are made up of irregular tissue crevices lined by a continuous attenuated endothelium, and collecting lymphatics with a smooth muscle media and the ability for spontaneous contractility. Virtually the entire array of mammalian organs with lymphatic drainage have initial lymphatics which are drained by collecting lymphatics, but in organs like skeletal muscle and intestine almost all lymphatics are of the initial type, and the muscular collecting lymphatics arise only outside the organs per se. How can interstitial fluid find its way into the sparely positioned initial lymphatics? Initial lymphatics exhibit no detectable contractile activity. Their endothelium shows incomplete attachment between neighbouring cells, providing a mechanism to open and close lymphatic endothelial microvalves along the walls of the initial lymphatics. Current evidence suggests that lymph fluid formation in the initial lymphatics requires periodic expansion and compression of the initial lymphatics. Expansion of the initial lymphatics causes filling by percolation of interstitial fluid across the open endothelial microvalves. Compression causes closure of the endothelial microvalves and outflow along the lumen of the microlymphatics with eventual transport into collecting lymphatics, towards the nodes and into the thoracic ducts. Reflow towards the initial lymphatics is prevented by valves. Expansion and compression of the initial lymphatics depend on deformation of the tissue in which they are embedded. In skeletal muscle, lymphatics are usually paired with arterioles so that vasomotion and arterial pulsations as well as muscle contraction may lead to periodic expansion and compression. In other organs alternative mechanisms are expected to operate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252624 TI - Morphological studies of the cardiac lymphatic system. AB - The distribution and structure of the mammalian cardiac lymphatic system have been investigated by puncture injection, intra-arterial injection of silver nitrate, hydrogen peroxide immersion, and light and electron microscopy. The cardiac lymphatic system consists of drainage vessels and lymphatic capillaries. The drainage vessels contain many valves and are mainly situated subepicardially following branches of the coronary artery. The lymphatic capillaries are composed of a thin layer of endothelial cells, and form relatively dense networks in a fishnet arrangement. These lymphatic networks are richer in the ventricles than in the atria, being present in the subepicardial myocardial and subendocardial regions. In addition, networks are found in all cusps of the atrioventricular valves, and in the sinuatrial node and atrioventricular system. The lymphatic system maintains cardiac homeostasis by receiving proteins, electrolytes and excess fluid from the interstitial tissue and returning them to the venous system. PMID- 2252625 TI - The intimate association of nerve terminals with the lacteal endothelium in the canine duodenal villi observed by transmission electron microscopy of serial sections. AB - A hitherto undescribed intimate association of the nerve fibers with the central lacteal endothelium in the canine duodenum was demonstrated by transmission electron microscopy of ultrathin serial sections. Around the proximal half of the entire extent of the central lacteal, there exist three to ten unmyelinated nerve fibers 0.1-0.15 microns in diameter. Some of these exhibit bulbar swellings (0.7 1.0 microns in diameter) which contain small clear vesicles (30-35 nm in diameter) and/or rather large vesicles (60-90 nm) with electron-dense cores (40 60 nm). Most of the bulbar structures of the nerve fibers are in contact with or surrounded by the central lacteal endothelial cells. These results suggest the existence of a neuronal control over the activity of the lacteal endothelial cells. PMID- 2252626 TI - The arrangement of collagen fibrils in the lymphatic sinus wall of the rabbit appendix. AB - The lymphatic sinus of the rabbit appendix was examined by scanning and transmission electron microscopy. Luminal surfaces of the sinus were lined by squamous endothelial cells, some of which, however, were blebby in surface relief due to the presence of electron dense granules in the cytoplasm. Many clusters of lymphocytes were present on the endothelial surface, mainly along the blood vessels of the trabeculae and of the sinus wall. Regional differences in collagen fibrillar arrangement of the sinus wall were demonstrated after the removal of the endothelial cells by the NaOH maceration method (OHTANI, 1987). In the upper region of the sinus and the lymphatic plexus of the internodular thymus dependent area (TDA), the fibrillar layer was a delicate network of interwoven thin fibrils. Furthermore, transmission electron microscopy revealed frequent transmural passages of lymphocytes, which suggest the existence of pores or fenestrations in the fibrillar layer of these regions. The fibrillar layer in the lateral and basal sinus was formed by densely interwoven thick bundles or sheets which consisted of thin collagen fibrils. No obvious space was seen between fibrils. These observations suggest that the upper region of the sinus and the lymphatics in the TDA may be active sites of cell migration from the reticular tissue. PMID- 2252627 TI - Organization of the lymphatic vessels and their relationships to blood vessels in rabbit Peyer's patches. AB - The three-dimensional organization of the lymphatic vessels and their relationship to blood vessels in rabbit Peyer's patches were demonstrated by scanning electron microscopy (SEM) of corrosion casts and of tissues. The interconnected central lacteals in the villi overlying the interfollicular area were connected with the lymphatic plexus in the area. There were many blind ending lymphatic vessels in the upper part of the interfollicular area. These lymphatics gradually fused and formed perifollicular lymphatic sinuses which surrounded the lateral surfaces and bottoms of the follicles. There were no lymphatic vessels within the dome and the follicle. The perifollicular lymphatic network surrounded the capillary network of the follicle. Between the perifollicular lymphatic networks in the interfollicular area were many high endothelial venules (HEVs) which collected the capillaries in the dome and the follicle. The voluminous perifollicular lymphatic sinuses seemed to have a great potential capacity as both reservoirs and as drainage routes for fluid and lymphocytes. The close association of HEVs with the perifollicular lymphatic vessels seemed to facilitate the prompt drainage of fluid and macromolecules leaking out of HEVs during lymphocyte migration into the lymphatics. That the HEVs are downstream of the capillaries in both the dome and the follicle suggests that substances such as cytokines may be involved in the induction of the post capillary venules into HEVs. PMID- 2252628 TI - Milky spots of the omentum: a source of peritoneal cells in the normal and stimulated animal. AB - The topography and ultrastructure of the omentum in normal and stimulated mice were investigated with combined transmission (TEM) and scanning electron microscopy (SEM). The present study demonstrated that lymphocytes and monocytes were the principle cell types in the non-stimulated milky spot. Following stimulation with bacterial toxin and adjuvant there was an increased microvascular permeability to fluid, neutrophils, monocytes and fibrin deposits within the connective tissue matrix of milky spots, and a subsequent increased cellular migration across the mesothelial lining into the peritoneal cavity. Cellular migration from the milky spot to the peritoneal cavity is facilitated by the absence of a basal lamina from the submesothelial connective tissue layer, therefore, cells can migrate from the interstitial spaces of the milky spot to intercellular gaps between mesothelial cells without having to penetrate a fibrous barrier. PMID- 2252629 TI - The liver lymphatics as a migratory pathway of macrophages from the sinusoids to the celiac lymph nodes in the rat. AB - A migratory pathway of macrophages as well as lymphatic communications from the liver to the celiac lymph nodes were studied both macroscopically and histologically. The injection of gelatinized carbon into the porta hepatis revealed a new pathway of the liver lymphatics running independently of the portal vein in addition to the ordinary periportal lymphatics. By obstruction of the efferent lymph flow of the celiac nodes and immunostaining with a monoclonal antibody to lymphatics, perilobular lymphatic vessels in the portal tract was readily demonstrated. It was suggested that heavily carbon-laden (HC) macrophages had migrated from the sinusoid into the interlobular connective tissue by 6 h after an intravenous injection of carbon, and then entered the lymphatic vessels of the portal tract. By 9 h to 12 h after carbon injection, HC macrophages started to migrate into the celiac nodes via the two lymphatic pathways. From the marginal sinus in the celiac nodes, they moved into the interfollicular area of the superficial cortex, then accumulated in the paracortex by 12 h to 24 h. They finally ended up in the corticomedullary junction. Migrating HC macrophages showed morphological homogeneity. The liver lymphatic pathway in the rat and a significance for the translocation and function of migrating macrophages were discussed. PMID- 2252630 TI - Macrophage and tissue changes in the developmental phases of secondary lymphoedema and during conservative therapy with benzopyrone. AB - The normal role that the macrophage plays in tissue homeostasis is presented along with the morphological and functional changes that occur to the macrophage population as the lymphoedema progresses from the latent to the chronic phase and then with the treatment with a representative benzopyrone called coumarin. Underlying the lymphoedema, there is a chronic inflammation. It is this, in association with the accumulating protein and the subsequent alterations it produces in the tissues that attract monocytes and macrophages to the affected area. Despite the fact that macrophages are facultative anaerobes, and that larger numbers than normal accumulate, the tissue conditions result in a depression in their activity levels. Apart from these tissue conditions there is the possible production of deactivating proteins such as transforming growth factor beta 1 and 2. Evidence for this deactivation comes from enzymatic studies in which levels of typical macrophage enzymes are reduced and from morphological work which has shown a reduction in pseudopods and a tendency to accumulate large amounts of lipid in their vacuoles. As a consequence of this deactivation further protein accumulation occurs thereby osmotically attracting fluid. Also there is a tendency for the tissues to become fibrotic as the balance between collagen lysis and deposition shifts towards the latter since it has been shown that macrophages have an important role in collagen lysis. The administration of coumarin stimulates the macrophages resulting to their return to normal or supranormal activity levels within the lymphoedematous tissues. As well as this there is an increase in macrophage numbers. The reasons for stimulation are uncertain, however, alterations in the fine structure of the proteins and complement which make these more attractive for phagocytosis seem the most likely. The end result is an rapid enhanced breakup of the excess interstitial protein and the removal of the osmotically attracted fluid together with a more gradual removal of the deposits of fibrotic tissue by the non-stimulated macrophage. Clinically this manifests itself as a softening of the tissues, a reduction in circumference of the lymphoedematous extremity, a return to normal tissue remodelling processes and a range of subjective improvements for the patient. PMID- 2252631 TI - Topographical anatomy of the bronchomediastinal lymph vessels: their relationships and formation of the collecting trunks. AB - This article aims to clarify the topographical relationships of the bronchomediastinal collecting lymph vessels to other structures, in particular the great vessels, the trachea, the esophagus and the mediastinal pleura. Minute dissection was performed on eight cadavers with special reference to the converging collecting lymph vessels which form the bronchomediastinal trunks. On the right side, the trunks were consistently observed on both the right brachiocephalic vein and the subserous surface of the mediastinal pleura (anterior and posterior mediastinal trunks). The pathway from the right recurrent chain nodes ran laterally behind the carotid sheath and led either into the deep cervical nodes situated on the scalenus anterior or directly into the right venous angle. On the left side, the trunks showed varying courses. The nodes from which the trunks arose were constant, and classifiable into three groups: the uppermost paratracheal nodes near the recurrent chain nodes, the anterior mediastinal nodes (the left phrenic nodes) surrounding the phrenic nerve in front of and inferior to the aortic arch (the origin of the superior mediastinal trunk), and the left tracheobronchial nodes (the origin of the inferior mediastinal trunk). The large transverse superficial communicating vessel between the right and left sides was usually found in front of the trachea above the aortic arch; it was often connected to the nodes of the brachiocephalic angle. Deep communications were also found in front of the carina and behind the trachea. These findings allow the collecting vessels from the thoracic viscera to be divided into two pathways on each side: the anterior and posterior mediastinal trunks on the right side, and the superior and inferior mediastinal trunks on the left side. In addition to the four trunks, the superficial communicating vessel between the right and left sides is also drained from the superior mediastinum. The internal mammary lymph chain, which often emptied directly into the venous angle or into the deep cervical nodes, occasionally joined with the right anterior mediastinal trunk or the left superior mediastinal trunk. PMID- 2252632 TI - A new approach for identification of rat lymphatic capillaries using a monoclonal antibody. AB - In order to discriminate rat lymphatics from blood vessels on tissue cryosections by immunohistochemistry, a mouse monoclonal antibody (B27) was produced by immunization of mice with a homogenate of rat thoracic duct. B27 strongly recognized endothelial cells of almost all rat lymphatics, such as lacteals, lymphatic capillaries in the diaphragm at sites of absorption from the peritoneal cavity, collecting lymphatics and the thoracic duct. Besides the lymphatics, B27 reacted with the endothelium of some types of blood vessel, the mesothelium of the peritoneal cavity and substances between smooth muscle fibers. A new double immunostaining technique was then developed to distinguish the lymphatic capillaries, having no or only scanty basement membranes more clearly from the blood vessels. Cryosections were stained first with an anti-type IV collagen antibody for basement membranes, secondly with B27 for the endothelium, and then examined by either light microscopy or fluorescence microscopy. With this technique, the lymphatic capillaries were easily distinguished from other vessels by their positive reaction with B27 alone. B27 appears to be very useful for the simple and reliable identification of rat lymphatics, particularly lymphatic capillaries, in various tissues when applied for double immunostaining. PMID- 2252633 TI - Enzyme-histochemical demonstration of intralobular lymphatic vessels in the mouse thymus. AB - Intralobular lymphatic vessels in the mouse thymus were demonstrated enzyme histochemically by combined light and electron microscopy. In sections reacting to both 5'-nucleotidase (5'-Nase) and alkaline phosphatase (ALPase), the intralobular lymphatic vessels were identified as irregularly shaped spaces with strong 5'-Nase activity. The lymphatic vessels were closely associated with the branches of ALPase-positive intralobular arteries and veins. The initial lymphatics, which presumably originate from the perivascular spaces, were 5'-Nase positive. The distribution and intensity of the 5'-Nase activity in the lymphatic vessels revealed by light microscopy correlated well with those by backscattered image electron microscopy. The backscattered image scanning electron microscopy of the same area as observed under a light microscope more clearly highlighted the peculiar contours of lymphatic endothelial cells. Transmission electron microscopy showed that specific reaction product of the 5'-Nase after incubation in a medium containing L-tetramisole was predominantly localized on the outer surface of the lymphatic endothelial cell membranes. PMID- 2252634 TI - Immunohistochemical differentiation between lymphatic vessels and blood vessels- use of anti-basement membrane antibodies and anti-factor VIII-related antigen. AB - Several immunohistochemical methods using Factor VIII-Related antigen (FVIIIR:Ag), laminin, Type IV collagen and fibronectin antisera were applied for the purpose of differentiating rat lymphatics from blood vessels by light and electron microscopy. Weibel-Palade bodies (WPB) were demonstrated in both types of vessels by conventional electron microscopy. The immunoreactivity to laminin and Type IV collagen in blood vessels showed a strong, continuous, linear subendothelial staining pattern in contrast to lymphatic vessels in which immunoreactivity was absent or weak in paraffin-embedded sections stained with the indirect immunoperoxidase technique. A positive reaction for fibronectin was observed in all extra-vascular tissue spaces as well as in lymphatics and blood vessels. FVIIIR:Ag and WPB were present in both lymphatic and blood endothelial cells. FVIIIR:Ag antiserum labeled with gold particles was observed only in the vacuoles which were assumed to be identical with WPB as demonstrated by our conventional electron microscopy. We conclude that the immunohistochemical method using laminin and Type IV collagen antisera is a reliable and practical way to differentiate lymphatic vessels from blood vessels by light microscopy. PMID- 2252635 TI - Corticosteroid modifications in HIV infection: a role for nonesterified fatty acids. PMID- 2252636 TI - Morphine-induced transactivation of HIV-1 LTR in human neuroblastoma cells. AB - Infection by human immunodeficiency virus (HIV) is followed in many cases by a clinically quiescent or latent phase that appears to continue as long as host antiviral defense is intact. This has raised the possibility that certain host susceptibility factors (i.e., environmental cofactors) might influence the progression of the disease. In this study we demonstrate that morphine can function to activate HIV/LTR-CAT fusion gene (HIV-long terminal repeat chloramphenicol acetyltransferase) when transfected into undifferentiated human SH-SY5Y neuroblastoma cells. The stimulatory effect of morphine is amplified in SH-SY5Y cells that have been induced to differentiate first with phorbol 12 myristate 13-acetate (PMA) and is much less in cells differentiated with retinoic acid (RA). Morphine does not appreciably activate HIV/LTR-CAT expression in human MOLT-3 and other T cells. Morphine activation of HIV/LTR-CAT in the SH-SY5Y cells is not reversible by naltrexone and appears to involve a Fos/Jun signaling system. Our results suggest that narcotics such as morphine may lead to activation of latent HIV infection. This may be particularly important in tissues, such as brain, which can host latent HIV infection and which is uniquely damaged in patients with acquired immunodeficiency syndrome (AIDS) as evidenced by neuronal degeneration and dementia. We also predict that these findings may have important implications for the pathogenesis of AIDS, particularly in opiate drug abusers. PMID- 2252637 TI - Naturally occurring HIV-1 isolates with differences in replicative capacity are distinguished by in situ hybridization of infected cells. AB - Replication of human immunodeficiency virus type 1 (HIV-1) isolates in peripheral blood mononuclear cells (PBMC) has been studied by in situ hybridization using the riboprobe BH10-R3 from HTLV-IIIB. Two series of isolates were tested: (a) 20 isolates from individuals with varying severity of HIV-1 infection and (b) sequential isolates from 5 subjects showing signs of clinical progression over a 45 month observation period. The results show that HIV-1 isolates with distinct replicative capacity can be distinguished by the intensity of radioactive labeling over single infected cells after in situ hybridization. Sequential isolates from patients with clinically progressive HIV-1 infection show a gradual increase in replicative capacity over time. In PBMC cultures infected with such sequential isolates, intensity of radioactive label over single infected cells increases and is strongest with isolates obtained at the time of low CD4 counts in blood. The results suggest that the restriction of virus replication that operates in the early stages of HIV-1 infection is gradually lost with progression of the disease. PMID- 2252638 TI - A semiquantitative microassay for measurement of relative number of blood mononuclear cells infected with human immunodeficiency virus. AB - A simple semiquantitative microassay was developed for the measurement of relative number of infected peripheral blood mononuclear cells (PBMC) from individuals infected with human immunodeficiency virus (HIV). The assay is based on cocultivation of serially diluted PBMC of a seropositive person with phytohemagglutinin-stimulated normal PBMC. The microassay has comparable sensitivity with the standard virus culture method in detecting positive HIV cultures. Since the microassay uses only 2-3 x 10(5) patients' PBMC, the assay is also most suitable for HIV isolation from HIV-infected infants or from AIDS patients with extremely low T-cell counts. The microassay can also be used to measure antiviral effects of a drug on persistent HIV infection in vitro. Because the microassay measures the relative number of infected PBMC, it can be readily used for following the quantitative antiviral effect of a drug in a clinical trial. PMID- 2252639 TI - Cumulative AIDS incidence and altered mortality from bacterial infections. AB - To determine whether populations with high cumulative incidence of acquired immunodeficiency syndrome (AIDS) experienced increased deaths from sepsis, central nervous system abscess, or endocarditis, New Jersey AIDS patients were grouped according to their age, sex, race, and residence-specific cumulative incidence of AIDS since the onset of the AIDS epidemic. Between 1980 and 1986, among 25-44 year olds in the highest cumulative incidence group for AIDS, sepsis mortality increased from 3.3 to 15.2 deaths/100,000/year, an increase of 11.9 deaths/100,000/year (95% confidence interval (6.9, 17.0) deaths/100,000/year); mortality from central nervous system abscesses increased from zero to 1.7 (0.1, 3.2) deaths/100,000/year; and mortality from endocarditis increased from 0.8 deaths/100,000/year to 2.4 deaths/100,000/year, an increase of 1.6 (-0.5, 3.7) deaths/100,000/year. Age-matched New Jersey patient populations with low cumulative incidence of AIDS did not sustain a similar increase. The HIV disease associated increase in sepsis mortality among young populations represents a new component of the substantial increase in U.S. sepsis mortality that occurred over the last two decades, but was previously limited to older populations. PMID- 2252640 TI - Morphometric analysis of recombinant soluble CD4-mediated release of the envelope glycoprotein gp120 from HIV-1. PMID- 2252641 TI - Circulatory support at the turn of the decade. A clinician's view. PMID- 2252642 TI - Artificial heart. Hemorrheology and transient ischemic attacks. AB - Hemorrheology was studied in patients undergoing artificial heart support as a bridge-to-cardiac transplantation. Abnormal hemorrheology was seen in two patients, one on a Jarvik-7 total artificial heart, and the other on a Novacor left ventricular assist device. Both of these patients suffered neurologic episodes. The rheology of these two patients coincided well with their clinical status, and was accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration, and platelet aggregation. Results show that improving hemorrheology may be a beneficial avenue to pursue in preventing or treating transient ischemic attacks or other complications in patients during support with mechanical devices. PMID- 2252643 TI - Patterns of bacterial infection in calves implanted with artificial hearts. AB - Device-related infection is one of the most serious potential consequences of total artificial heart (TAH) implantation. This complication must be addressed before the full potential benefit of these devices, especially fully implantable devices, can be realized. A review of research reports and clinical data was conducted to ascertain if similarities existed between the patterns of infection reported in human TAH recipients and those seen in the experimental animal models. Infection was reported in approximately 57% of the human TAH recipients and approximately 47% of the implanted animals. Implant periods ranged from 1-620 days for the humans, and 32-287 days for the animals. The spectrum of organisms isolated from both groups were similar, with a high proportion of infections caused by Pseudomonas aeruginosa and Staphylococcus epidermidis. In addition, numerous isolates of Enterobacter and Enterococci were obtained from the animals. Positive blood cultures have often been observed in animals within 2-4 weeks following implantation of the devices. The similarities noted in this review suggest that the calf may be an appropriate animal model in which to study the pathogenesis of TAH-related infection. PMID- 2252644 TI - Combined administration of protease inhibitor and thromboxane A2 synthetase inhibitor for anticoagulation of a left ventricular assist device. AB - To establish ideal anticoagulant therapy for left ventricular assist devices (LVADs), a comparative study was made of a thromboxane A2 synthetase inhibitor, a protease inhibitor, and combined administration of the two. Results of the investigation indicate that combined administration of a thromboxane A2 synthetase inhibitor (OKY-046) and a protease inhibitor (nafamostat mesilate, FUT 175) provides ideal anticoagulant therapy during cardiac support using LVADs from the point of blood coagulation and fibrinolysis. Artificial hearts have come into practical use as left ventricular assist devices, and have contributed to the saving of many patients with severe postoperative low cardiac output syndrome, but they sometimes encounter severe complications, i.e. cerebrovascular bleeding, thromboembolism, infection, or multiple organ failure. It is very important, therefore, to control coagulation and fibrinolysis adequately during cardiac support by an LVAD. PMID- 2252645 TI - Shortening of the hemodialysis procedure and mortality in "healthy" dialysis patients. AB - The influence of shortening chronic hemodialysis on mortality was studied by following cumulative survival in "ideal" nondiabetic dialysis patients, who had no other diseases besides their renal disease when beginning dialysis. It was hoped that thereby problems of shortening dialysis could be separated from problems inherent in the patient. Otherwise healthy dialysis patients (n = 556) were divided into age groups (less than 50, 51-75, and greater than 75 years) and studied during four periods, 1966-75, 1976-82, 1983-85, and 1986-88. Dialysis time was shortened from 17 to 2.7 hr per treatment during that time, but a Kt/V of 1.3 maintained. Generally, both first- and four-year cumulative survival improved as dialysis was shortened, and four-year cumulative survival was best in all age groups during 1986-88 when dialysis was shortest. During this time, the four-year cumulative survival was no different from that of the age-matched total U.S. population. Shortening of dialysis time and increasing efficiency while keeping at least a 4.0, stable, weekly Kt/V has not been harmful to healthy patients on dialysis, but has led to continued improvement on cumulative survival. PMID- 2252646 TI - Morbidity and mortality in hemodialysis patients. AB - Increase in mortality in hemodialysis patients in the United States is a rising concern. In this study, the annual mortality rate from 1981 to 1989 was determined and the morbidity and mortality of 136 patients dialyzed during 1988 was analyzed. All patients were followed with urea kinetics (UK). Patients were divided according to NCDS mapping of BUN and protein catabolic rate (pcr): Group 1, inadequate protein intake (n = 28); Group 2, adequate dialysis (n = 51); Group 3, excessive dialysis (n = 28); Group 4, undefined domain (n = 13); and Group 5, transitional domain (n = 16). The UK parameters measured were midweek predialysis BUN, pcr, and Kt/V. Group 1 by definition had the lowest pcr (0.7 g/kg/day vs. greater than 1.0 in the other groups). Patients in Group 1 had significantly lower BUN, creatinine, hematocrit, and serum albumin. Results of all other laboratory tests were not significantly different. Numbers of hospitalizations and days in the hospital were higher in Group 1. Causes of hospitalization were similar in all groups. Mortality rate was 8% in Group 1 vs. 4.4% in Group 2. Dialysis prescription using UK has maintained the annual mortality rate at about 14% for the past nine years. PMID- 2252647 TI - Kt/V and hemodialysis morbidity revisited. AB - Analysis of the National Cooperative Dialysis Study (NCDS) showed that dialysis morbidity was related to Kt/V. Recently, various formulae have been shown to be accurate for easier calculation of Kt/V. We calculated Kt/V in an outpatient unit utilizing Kt/V = -In (R - 0.03 - UF/W) in 51 patients. Kt/V was less than 0.8 in 16 patients (Group A), 0.8-1.0 in 20 (Group B), and greater than 1.0 in 15 (Group C). There was no difference in hematocrit (Hct), BUN, creatinine, serum phosphorus, and albumin. Ratio of men to women was 11/5, 15/5, and 4/11; mean age was 54, 63, and 58 years; mean body weight 177, 144, and 122 lb in Groups A, B, and C, respectively. Dialysis-related hospital admissions were similar (p greater than 0.05). These data suggest patients with higher body weights, and men, frequently had a Kt/V less than 0.8. Kt/V that did not influence biochemical parameters or hospitalizations in this population. This indicates that Kt/V may not be a good predictor of morbidity, and/or some heavier patients may do fairly well even with a Kt/V less than 0.8. The search for a better index of dialysis adequacy should be continued. PMID- 2252648 TI - Income and survival in chronic dialysis patients. AB - The relationship between income and survival rates for chronic dialysis patients in Michigan was examined. To evaluate the relative risk (RR) of dying, by income, a Cox survival regression model was used to adjust for age, race (black versus white), gender, dialytic treatment modality, year of first end-stage renal disease (ESRD) therapy, and primary cause of ESRD. The average household income reported from census data for the ZIP Code of residence for each patient was analyzed as a socioeconomic indicator. Treatment modality on day 120 of ESRD was classified as either center hemodialysis (HD) or CAPD. All new patients, aged 20 59 and registered at the Michigan Kidney Registry between 1/1/80 and 12/31/87 were included in the study. Patients were followed from day 180 of ESRD until death, censoring at transplant, or 12/31/87. The adjusted relative risk of dying decreased for black patients by 3.3% per $1,000 increase in income (p less than 0.01), while the trend by income for white patients was negligible (p greater than 0.10). The difference in trends for the two groups was statistically significant (p less than 0.01). This is a surprising result, since white patients have higher death rates, overall, than do black patients, particularly among subgroups with diabetes and hypertension whose RR was 1.77 and 1.82, respectively. Poor socioeconomic status of the area of residence has a strongly negative effect on survival for black patients, but not for white patients. The reasons for the relationship of death rates with income, especially for black patients, need to be examined in greater detail. PMID- 2252650 TI - Endothelialization on various segmented polyurethanes: cellular behavior and its substrate dependency. AB - Endothelialization on artificial substrates is essential for providing vital function to artificial and hybrid vascular prostheses. The authors studied fundamental behaviors of endothelial cells (EC), including adhesion, spreading, migration, and growth, on various segmented polyurethanes (SPU) with a wide variety of wettability. Endothelialization has a synergistic action on these cellular behaviors that was quantitatively evaluated by phase contrast microscopy. Surface characteristics of SPU were analyzed by contact angle measurement and X-ray photoelectron spectroscopy. Adhesion, spreading, migration, growth, and endothelialization in vitro of bovine aortic EC on relatively hydrophobic SPU exceeded those on both a hydrophilic SPU, and a very hydrophobic siliconized one. Minimal interaction with EC was found for hydrophilic SPU. Adherent cells tended to be delaminated from siliconized SPU in a later culture period. The addition of a peptidyl antagonist of adhesive protein receptor inhibited adhesion of EC on SPU. These results suggest that surface characteristics, possibly regulating adsorption of adhesive proteins, are important factors in the development of vascular SPU prostheses. PMID- 2252649 TI - Novel photoreactive surface modification technology for fabricated devices. AB - A novel surface process technology was developed to improve biocompatibility of fabricated devices, such as artificial blood pumps. The developed technology is based on photochemistry of a phenyl azide group, which is capable of covalently binding a synthetic polymer or protein to substrate surfaces upon ultraviolet (UV) irradiation. The photoreactive co-polymers or proteins, which were grafted or modified with phenyl azide groups, were successfully chemically fixed to surfaces. Photoreactive, hydrophilic copolymers with poly(dimethyl acrylamide) and albumin, both of which were chemically fixed on surfaces, were found effective for blood compatible surfaces; a fibronectin-bound surface was suitable for providing tissue compatibility. The quartz optical fiber guided UV irradiation system enables one to provide desired biocompatibility to a specific part of a fabricated device. PMID- 2252651 TI - In vivo nonthrombogenicity of heparin immobilized polymer surfaces. AB - The authors developed two different methods to immobilize heparin on polymer surfaces. One method involves in situ heparin immobilization on a segmented polyurethane urea (Biomer) surface via hydrophilic poly(ethylene oxide) (PEO, Mn = 4,000) spacers. The other method uses PEO/poly(dimethylsiloxane) (PDMS) block co-polymer and heparin covalently linked in a block co-polymer system (PEO-PDMS Hep). These surfaces have demonstrated high heparin bioactivity in vitro and excellent blood compatibility in in vitro-ex vivo experiments. This report evaluates the long-term in vivo blood compatibility of these heparin immobilized surfaces. Vascular grafts (6 mm ID, 7 cm in length) were fabricated with Biomer, and heparin was immobilized in situ with PEO spacers (B-PEO4K) and coated on their luminal surfaces with PEO-PDMS-Hep. Biomer and PEO (Mn = 4,000) grafted Biomer (B-PEO4K) were used as controls. The grafts were implanted in the abdominal aorta of dogs and retrieved at 3 months or when graft occlusion was suspected. Retrieved grafts were evaluated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). TEM measured the thickness of the adsorbed protein layer on the surface and the protein distribution (albumin, fibrinogen, and IgG) visualized by an immunogold method. All heparin immobilized grafts were patent at 3 months, whereas Biomer and B-PEO4K grafts occluded within 1 month. SEM pictures of heparin immobilized surfaces after 3 months demonstrated minimal platelet adhesion and activation without detectable fibrin formation. Heparin immobilized surfaces showed a thin protein layer (300-600 A) even after 3 months, with high concentrations of albumin and IgG and less fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252652 TI - Complement activation and use of a cell saver in cardiopulmonary bypass. AB - Complement activation was evaluated in ten patients undergoing cardiopulmonary bypass (CPB) and intraoperative blood salvage with a cell saver (CS) to assess the inflammatory response related to the CS. The washed red blood cell concentrate was reinfused after protamine injection. Plasma C3a was measured by radioimmunoassay preoperatively, 5 min before CPB, at 5, 60, and 90 min during CPB, 5 min after protamine infusion, at the end of surgery, and after 24 hr. In addition, a clinical score based on renal, pulmonary, neurologic, and myocardial postoperative evolution was given (0-8) to every patient. Results were compared with the C3a changes and clinical scores obtained from 26 routine (no CS) cardiac surgical patients. Results showed maximal C3a generation after protamine and no further activation in cases of CS concentrate reinfusion, which ranged from 400 ml to 2,000 ml. No difference in clinical score was observed between the CS (1 +/ 1) and control (0.85 +/- 0.6) groups. The authors conclude that the CS does not enhance complement activation resulting from extracorporeal circulation and can be safely used as a blood saving strategy in cardiac surgery. PMID- 2252653 TI - Biomaterial calcification without direct material-cell interaction. AB - This report summarizes 1) features of the local redistribution of calcium ions and formation of complexes with calcium (Ca) in the presence of polymer samples; 2) the adsorption of Ca ions and Ca containing complexes onto biomaterial surfaces; 3) the character and composition of Ca containing deposits; and 4) the role of cellular and humoral factors in calcification. All experiments were done with three types of medical grade polymer material (from USSR): silicone rubber (SR), polyurethane "Vitur" (PU), and polyethylene (PE). Biochemical, radioisotopic, SEM, and EDAX methods were used in in vitro and in vivo experiments. The diffusion chamber model was used in animal experiments. SR was shown to induce greater changes in complex formation processes and to adsorb more Ca containing complexes than PE or PU. In addition to the degree of SR calcification seen after 21 days, implantation accentuated these findings. The possibility of calcification of polymer materials without direct contact of material and cells was observed. Combining the in vitro and in vivo experimental data, the authors propose a hypothetical scheme of biomaterial calcification. PMID- 2252654 TI - Differential light scattering cuvettes for the measurement of thromboemboli in high shear blood flow systems. AB - Newly developed optical scattering cuvettes were constructed as a modification of our existing 1.0 mm and 3.0 mm internal diameter (ID) cuvettes to facilitate the measurement of platelet microemboli ranging from 20 microns to 1,000 microns diameter in whole blood in 0.9 mm ID flows ranging from 250 to 4,000 ml/min. A perturbation solution to the one-speed radiative transport equation was used in the design and calibration of these cuvettes. A series of tests were performed with these cuvettes in an extracorporeal left ventricular assist device bovine model, and in a recirculating closed-loop flow system containing anticoagulated whole baboon blood, to determine to what extent they affect platelet and erythrocyte function ex vivo and in vitro. Serial hemolysis tests, thromboxane radioimmunoassay measurements, platelet counts, and activated partial thromboplastin times were measured. All of these tests with cuvettes in the extracorporeal and in vitro circuits were statistically indistinguishable from baseline measurements, suggesting the usefulness of this system for the measurement of microemboli in blood-contacting materials of extracorporeal circuits and cardiac assist devices. PMID- 2252655 TI - Shear stress induces not only platelet aggregation but also platelet-tumor cell interaction. AB - To investigate the interaction between platelets and tumor cells under well defined flow conditions, the effect of tumor cells on platelet aggregation induced by shear stress was studied using a cone and plate viscometer adapted for measuring transmitted light intensity. Aggregation was markedly enhanced by HMV-1 cells in a cell number-dependent fashion under shear stress of 12 dyne/cm2. Enhancement was not observed at a high shear stress of 108 dyne/cm2. A monoclonal antibody against GPIIb/IIIa, 7E3 completely abolished enhancement of aggregation by HMV-1. Apyrase had similar inhibitory effects. Scanning electronmicroscopy showed that direct contacts of platelets with HMV-1 cells could be demonstrated when platelet-platelet interaction was inhibited by 7E3 or apyrase. These results may indicate that, at a shear stress of 12 dyne/cm2, direct contacts of platelets and HMV-1 cells may trigger enhancement of platelet aggregation. PMID- 2252656 TI - Development of a new transvenous patent ductus arteriosus occlusion technique using a shape memory polymer. AB - A novel percutaneous patent ductus arteriosus (PDA) occlusion technique, without the potential problems associated with conventional techniques, has been long awaited. The development of a novel transvenous PDA occlusion technique using a temperature-shape changeable occluder device, and the verification of its in vitro performance, were demonstrated in this study. The principles of this technique are: 1) the bar form device was inserted into the PDA transvenously by a guide wire and a pushing catheter, 2) the device was dashed with hot water through catheters, 3) the device was expanded by hot water in the PDA, and the PDA was occluded. The occluder device, made of a shape memory polymer (polynorbornene), was designed to have the monobloc configuration of a thin disk with a hole for a guide wire in the center and a cone. The barlike device by hot press was fully expanded within 10 sec upon immersion into 45 degrees C water. The mock-circulation test with the "great arteries" and a specially designed "PDA" showed 1) the introduction of hot water (45 degrees C) through the catheters caused expansion of the device which stayed in the "PDA" without any support, 2) the "aortic" pressure and the distal "aortic" flow increased rapidly, and the "pulmonary" flow reduced promptly. This resulted in a drastically reduced shunt ratio at the PDA from 68% to 30%. Thus, the novel PDA occlusion technique developed here functioned well to occlude the PDA in a great arteries model. PMID- 2252657 TI - Effects of retrovenous myocardial drug delivery after coronary artery occlusion in sheep. AB - Retrovenous (RV) myocardial delivery of blood and drugs into the coronary sinus (CS) through a 3 lumen balloon catheter was evaluated in sheep (no coronary collaterals) for protection from ventricular fibrillation (VF) during coronary artery occlusion. The balloon was asynchronously inflated (CS occlusion) for 5 sec and then deflated for 5 sec with 1 cc/sec of flow. The left anterior descending coronary artery was occluded with inflation of a percutaneous transluminal coronary angiography balloon and therapy started immediately. In a control group (no therapy, n = 4) all developed VF by 30 min after coronary artery occlusion. The drugs lidocaine (L), esmolol (E), adenosine (A), and deferoxamine (D) were evaluated for effects on eliminating developing VF with intravenous (i.v.) administration compared with RV administration with venous blood (VB) or arterial blood (AB). The percent survival after CA occlusion (no VF) was: L i.v., 0%; L RV with VB, 43%; L RV with AB, 17%; E i.v., 50%; E RV with VB, 70%; A. i.v., 29%; A RV with VB, 88%; D i.v., 17%; and D RV with AB, 80%. There was a trend toward lower myocardial necrosis (seen by tetrazolium stain and/or light microscopy) in the RV survivors (especially with VB) compared with the group i.v. survivors. These data suggest that RV antiarrhythmic drug delivery is a feasible alternative to i.v. administration during CA occlusion. PMID- 2252658 TI - Safety, stability, and effectiveness of immunoadsorption under membrane plasmapheresis treatment for myasthenia gravis. AB - Nine patients (five women and four men, average age 50.4 years) with refractory myasthenia gravis (MG) underwent thymectomy and were then treated with immunoadsorption under membrane plasmaphersis (IAP). Thymic histology showed hyperplasia in nine patients. An immunoadsorption column (ASAHI, Med, Co) was made with tryptophan. A Plasouto 1,000 (ASAHI, Med, Co) was used as the machine. The plasma separator was a first filter (ASAHI, Med, Co), and immunoadsorption columns were used for plasma perfusion. IAP treatment was performed three times weekly for a total of six times, after which IAP was done every 3 weeks. The removal rate of anti-Ach-R titer was 54 +/- 12%; IgG, IgA, and IgM levels improved in nine of nine patients after IAP treatment, and improvement of gait disturbances were seen in two of two. Muscle strength improved in all nine patients, whereas speech disturbances improved in two of three. Eye ptosis improved in nine of nine patients. Subjective improvement was reported by nine of nine patients, and none had severe side effects with IAP. In conclusion, IAP is a safe, stable, effective, and clinically useful treatment. for MG. PMID- 2252659 TI - Basic studies on a new material for inducing antitumor immune cells. AB - Recently, adoptive immunotherapy for cancer with lymphokine activated killer (LAK) cells has been widely used experimentally. The therapy has several problems, including difficulty in handling, sterilization, and time consumption. To solve these problems, new materials able to induce antitumor immune cells were investigated. Pokeweed mitogen (PWM) and PWM-conjugated materials (CMC-1) could induce strong killer cells by short-term stimulation of human peripheral blood lymphocytes (PBL). The induced killer cells showed a wide killing spectrum in vitro against human tumor cell lines (MKK-1, PRMI4788, NBT-2, ZR-7530, H-1, Hela, KB, HMV-1, PC-10, C-1). Human PBL stimulated for a short time by CMC-1 also showed a tumoricidal effect on tumor bearing (MKN-1, MKN-45) nude mice. These results suggest that CMC-1 may solve the problems with currently used LAK therapy and may provide easily applicable extracorporeal immunotherapy for cancer. PMID- 2252660 TI - Non-heparin hemodialysis with oral administration of newly developed antiplatelet agent. AB - Non-heparin hemodialysis (HD) was successfully done in anuric dogs with the oral administration of a newly developed antiplatelet agent, 4-cyano-5,5-bis(4 methoxyphenyl)-4-pentenoic acid, (E5510, Eisai Pharmaceutical Co., Japan). In the current study, the antithrombotic effect of E5510 during HD was investigated. Eleven mongrel dogs with bilateral ureteral ligation were given 0.1 mg/kg of E5510 orally 1 hr before undergoing 4 hr HD using hollow fiber dialyzers, (PMMA 5, regenerated cellulose 6) without heparin and under general anesthesia. Blood samples were taken before the administration of E5510 and before and 1, 2, 3, and 4 hr after starting HD; blood counts, hematocrits, blood chemistries, and plasma thromboxane levels (TxB2) were examined. Platelet aggregation, activated clotting times (ACT), and activated partial thrombin times (APTT) were also measured, and sequential plasma E5510 concentrations were determined. In 10 of 11 anuric dogs, non-heparin HD was successfully done with minimal clotting in the dialyzer and drip chambers. The maximum aggregation rate was depressed to less than 20% of the initial value throughout HD. Plasma TxB2 concentration was depressed, and ACT and APTT were mildly, but not significantly prolonged. Neither hemorrhagic complications nor other side effects of E5510 were observed. PMID- 2252661 TI - Cardiac arrest after hypertonic citrate anticoagulation for chronic hemodialysis. AB - The use of regional citrate anticoagulation as an alternative to standard therapy in hemodialysis patients at risk for bleeding complications has been well described. Recently, a method using hypertonic citrate has been reported as being safe and efficacious, and having several advantages over the usual techniques. Two patients who suffered cardiac arrests after dialysis using hypertonic citrate are discussed. Both received anticoagulation as described in the literature, although the citrate infusion rate was lower than recommended. Electrocardiograms obtained during the first such session showed no change in the Q-Tc interval with initiation of the infusion in either patient. Both were noted to have cardiac arrest within 5 minutes of discontinuation of dialysis, without warning symptoms, following the second and fifteenth treatments, respectively. The initial rhythm of ventricular fibrillation did not respond to standard advanced cardiac life support therapy, and the patients were not successfully resuscitated until they received intravenous calcium. The authors postulate that the loss of positive calcium flux from the dialysate, in conjunction with circulating unmetabolized citrate, caused an electrolyte imbalance leading to the potentially fatal arrhythmia. Caution is recommended in using this method of regional anticoagulation. PMID- 2252662 TI - Effectiveness of low dose erythropoietin: a possible advantage of high flux hemodialysis. AB - Recombinant human erythropoietin (EPO) was administered to 32 stable out-patients with end-stage renal disease (ESRD) on a priority basis three times a week. All patients underwent dialysis with polysulfone hollow fiber dialyzers. Mean time averaged blood urea nitrogen (BUN) value was 50 +/- 12 mg/dl, and Kt/V for urea was 1.20 +/- 0.34/dialysis. The initial dose of EPO was 2,800 +/- 950 U/dialysis (45 +/- 17 U/kg/dialysis). The maintenance dose averaged 2,500 U/dialysis. Within the mean time of observation, 15 +/- 4 weeks, all but one patient responded to EPO by eliminating transfusion requirements, and 29 of 32 achieved the target hematocrit of 30-33%. For patients with hematocrits below 25% before EPO, the increase averaged 1.6 +/- 0.8%/week. The dose of EPO was lower and the hematocrit response was higher than reported previously. The rate of increase in hematocrit did not correlate with small molecular weight solute removal. Mean red blood cell survival was 52 +/- 18 days. No adjustments in blood pressure (BP) medications or dry weight were required to control BP. These data and earlier experiences with recovery from the anemia of ESRD after more effective dialysis suggest that the bone marrow response to EPO may be augmented by high flux hemodialysis. PMID- 2252663 TI - A total artificial heart for neonates allowing bridging to transplantation. AB - Since the early 1980s, a rapid increase in successful pediatric heart transplantation has improved the chance of survival for many children suffering from otherwise fatal cardiomyopathies or congenital cardiac defects. During the last 5 years, heart transplantation in neonates and infants (0-28 days and 1-12 months, respectively) has been the most rapidly growing area within the pediatric patient population. No adequate mechanical circulatory support system, designed to be used as a bridge to transplantation, is available for many of these pediatric patients. Neonates are the smallest candidates to potentially benefit from heart transplantation, and their often acute need for either heart transplantation or temporary circulatory support indicates that any new development of a pediatric bridging device should focus on this youngest group. Subsequently, such a device may be modified to any weight or age group. An innovative total artificial heart design was developed in an attempt to meet the anatomic and physiologic requirements of neonates and infants. This report discusses the rapidly growing pediatric heart transplantation patient population, as well as an innovative total artificial heart design. PMID- 2252664 TI - Design mediated thrombus reduction in the Utah-100 total artificial heart. AB - The Utah-100 total artificial heart was initially designed and tested in 1983. General design goals, including improved fit for human application, improved reliability, and elimination of thrombus formation, were identified as improvements over the clinically used Jarvik-7 artificial heart, previously developed at the Institute for Biomedical Engineering, University of Utah. Specific design goals included 1) elimination of connector and valve-associated thrombus formation and 2) elimination of gross mineralization, thrombus formation, and creases on the blood-pumping diaphragm of the device. Explant retrieval results from 29 calves and sheep implanted with the Jarvik-7 artificial heart were compared with results from 25 calves and sheep implanted with the Utah 100 artificial heart. Macroscopic thrombus formation was found in 44% of the connectors of the Jarvik-7 artificial-hearts, compared with 2% (p less than or equal to 0.01) in animals with the Utah-100 artificial heart. Subvalvular and supravalvular thrombi were observed in 33% of the valves in the Jarvik-7 artificial heart and 10% (p less than or equal to 0.01) of the valves in the Utah 100 artificial heart. Mineralization of the pumping diaphragm was observed in 12% of the animals implanted with the Jarvik-7 artificial heart and in 4% of the animals with the Utah-100 diaphragms. Thrombus formation in the diaphragm-housing interface occurred in 2% of Jarvik-7 ventricles and in 6% of the Utah-100 ventricles. There were no identifiable diaphragm creases in the Utah-100 diaphragms, but a 10% incidence was found in Jarvik-7 devices. These results validate substantial progress toward improved design and fabrication methods in the Utah-100 total artificial heart. PMID- 2252665 TI - Development of the E4T electrohydraulic total artificial heart. AB - A completely implantable total artificial heart (TAH) is being developed based on many years of research performed at the Cleveland Clinic Foundation and Nimbus, Inc. The pumping unit consists of biolized surface-treated pusher plate blood pumps powered by an interventricular electrohydraulic energy converter. A variable volume device references the back side of the pusher plates to lung pressure. Electrical power is supplied by a transcutaneous energy transmission system, integrated with a wearable external battery pack. An implanted internal battery provides back-up power. System design and optimization efforts have resulted in a compact pumping unit package and an overall TAH that meets anatomic, physiologic, and engineering requirements. Overall pumping unit basic dimensions are 98 mm diameter and 80 mm thick. The blood pumps have a truncated conical shape and are separated by a thin interventricular septum 21 mm thick. Theoretical stroke volume is 64 ml, and maximum stroke length is 13.2 mm. Normal pump operation is at 90% of full stroke, which yields a net output of 53 ml, with valve regurgitation taken into account. PMID- 2252666 TI - Soft artificial ventricles for infants and adults, with or without a clamshell. AB - The quick connect system and mechanical disk valves used in total artificial hearts (TAH) are sources of thrombogenesis and blood damage. Our soft TAH, which has no quick connectors, can be squeezed and bent, making it easily implantable, and blood damage is reduced by the use of trileaflet and biflap polyurethane valves. The soft ventricles were made by vacuum forming, after which the pieces were welded together by radiofrequency heat sealing. A rapid clamshell can be pushed and slipped over the soft heart to prevent deformation of the ventricle. Three calves have had the 60 cc soft TAH implanted, both with and without a clamshell. The cardiac outputs were as high as 7 L/min, without a vacuum applied during diastole. Two lambs received the 20 cc TAH (as an acute experiment); it fit and functioned well. One healthy lamb received a 20 cc left ventricular assist device (LVAD) with a pulsating artificial atrium as a survival experiment. The lamb survived for 8 days, after which the device was removed and the lamb returned to the meadow. Thrombosis in the TAH was minimal, and the plasma free hemoglobin values in all the TAH and LVAD experiments were usually lower than 5 mg/dl and often lower than 2 mg/dl. PMID- 2252667 TI - An electrohydraulic total artificial heart with a separately placed actuator. AB - An electrohydraulic total artificial heart (EHTAH) system, consisting of a separately placed actuator and blood pumps with good anatomic fit, was designed. In the actuator is a brushless DC motor sandwiched between two metal bellows or two pusher-plate pumps connected with the blood pumps by polyvinylchloride tubes. A roller-screw system coupled with the bellows is used for alternative pumping, and silicone oil transmits the action. The pumps are elliptical, and the right pump has a flatter and longer shape than the left to fit the extremely short distance between the right atrium and the sternum. To evaluate in vivo performance, the pumps were implanted as a pneumatic system in a calf weighing 53 kg and three goats weighing 54-55 kg. The pump fit well in the animals, and the calf survived for 111 days, and one goat was alive for 8 days. The EHTAH system could provide an output of 6 L/min with pusher-plate pumps as oil chambers on in vitro evaluation. This system could become one of the most suitable approaches for a totally implantable system. PMID- 2252668 TI - Development of an efficient electrohydraulic total artificial heart. AB - The efficient use of space and energy is achieved in a new implantable total artificial heart (TAH). To fit the orthotopic thoracic space, toroidal blood pumps encircle an energy converter, consisting of a centrifugal hydraulic fluid pump and a rotary reversing valve. The new centrifugal pump produces cardiac outputs of 6 L/min, with an average hydraulic efficiency of 47%. Toroidal blood pumps encircling the pump deliver a 60 cc stroke with an 85% ejection fraction and have a predictable blood flow pattern with no stagnant regions. Components have been characterized in vitro, and blood contacting elements have been tested in vivo. PMID- 2252669 TI - A tether-free, moving actuator total artificial heart. AB - An electromechanical moving-actuator TAH was developed and implanted for 5 days in a calf experiment. The efficiency and durability were further improved using pendulous motion of the actuator. This new pendulum pump has a circular motion produced by gear mechanisms connected to the motor. It has a height (from valves to housing bottom) of 7 cm and centrally directed inlets and outlets for good fittability. Active filling (-10 mmHg) inside inner blood sacs was produced by the suction effects of the outer sacs attached to a moving actuator. Two acute animal experiments were performed using the pendulum pump with a Coridale sheep (50 kg weight), and a male calf (70 kg weight). A test was made of 30 minutes of tether-free operation of the implanted pendulum pump inside the small chest of the calf. The pump shows the engineering feasibility of the implantable electrical TAH inside a human chest cavity. PMID- 2252670 TI - Computer simulation of the circulatory system during support with a rotary blood pump. AB - In order to investigate the performance characteristics of nonpulsatile centrifugal pumps and their interaction with the pulsating heart, a computer simulation model was developed. A model of the pump, including the cannulae and the interference of the cannula and the left atrial wall, was added to a simulator of the circulation. It was implemented on a PC-AT using the analog simulating software AGO1000. An interval of 1 msec real-time per calculation step was evaluated to provide stable results. The calculation speed was approximately 100 msec per step. First simulation studies showed that both the positioning and resistance of the cannulae exert a major influence on system performance and equalized the different pressure-flow characteristics of vaneless and impeller pumps (difference of dp/dQ decreases from more than 6 times without cannulae to 130% with cannulae). In addition, the effects of suction in the atrial cannula, and changes of ventricular performance during changes in pumping power, could be properly simulated. The comparison with animal tests proved that the model is a suitable tool for testing control algorithms for centrifugal pumps. PMID- 2252671 TI - In vitro analysis of an atrial shunt in balancing an electrohydraulic total artificial heart. AB - In vitro tests were performed to evaluate the use of an interatrial shunt in balancing a dual energy converter, actively filled, volumetrically coupled, electrohydraulic total artificial heart. The in vitro atrial shunt was comprised of a 8 mm (PTFE) Teflon graft placed between the left and the right atrium. Other features under study were 1) cardiac output (CO) response to preload, 2) CO relationship to mean aortic pressure, and 3) balance of ventricular outputs. The tests were performed by varying the right filling pressure and monitoring ventricular output and inflow/outflow pressures. Effects of changes in afterload were simulated by varying the (AoP) pressure from 80 mmHg to 120 mmHg, and the (PAP) pressure from 15 mmHg to 40 mmHg. The test results indicated a rise in CO from 4 L/min to 9 L/min, with a change in mean right atrial pressure from 0 mmHg to 12 mmHg. No significant difference in CO was found as afterload pressures were varied. The interatrial shunt (IAS) was effective in establishing ventricular balance over a wide range of preload and afterload conditions, and a mean positive flow from left to right was maintained in the atrial shunt, even at conditions simulating an extreme left-right imbalance. PMID- 2252673 TI - An artificial heart driven by liquid gas. AB - An artificial heart (AH) driving system, in which a sac or diaphragm type blood pump is liquid gas driven, is designed. The working mechanism of this system is as follows: 1) liquid gas is used for the driving source; 2) a liquid gas is stored in its liquid state in the circuit; 3) a liquid gas is vaporized, and the vaporizing pressure squeezes the blood pump, causing ejection of blood; 4) vaporized gas is aspirated and compressed by a small compressor to liquefaction through the heat exchanger, then negative pressure is applied to the blood pump and blood is aspirated; and 5) the blood pump is driven in this closed cycle. To demonstrate the mechanism of this system, a prototype was developed using Freon 114 as the liquid gas. In this system, the maximum flow of the AH at a 100 pulse per minute rate, was about 6.9 L/min, using a 90 ml sac type blood pump. The advantages of this AH driving mechanism are as follows: 1) a small system is available because pressure chambers are not necessary; 2) a biventricular system is available, with a single compressor; 3) no compliance chamber is necessary if the system is small enough to be implanted. PMID- 2252672 TI - Another way of pumping blood with a rotary but noncentrifugal pump for an artificial heart. AB - This article describes an alternative mode of pumping blood inside the body. The device is a non centrifugal, valveless, low speed rotary pump, electrically powered, based on Wankel engine principle. The authors developed an implantable electrical actuator resulting in a compact, sealed motor-pump unit with electrical and magnetic components insulated from fluids. The results in the flow curve and in the pumping action show some common points but also some basic differences compared to classical pulsatile pumps or centrifugal pumps. The blood coming from the atrium follows a continuous movement without any stop flow but with variations creating pulsatility. Ejection and filling of the pump are simultaneous. It is always an active filling. Hydraulic efficiency depends on clearance in the pumping chamber and outlet port pressure. A 60 cc device allows flows up to 8-9 liters. The implantable motor is cyclindrical in shape, has a moderate weight (490 grams) and presents a good efficiency (32% for a rotary speed of 90 rpm against a mean aortic pressure of 150 mm of Hg). The authors conclude that their device could be proposed after further experimental studies, as an LVAD for shortterm assistance with a good promise for permanent application. PMID- 2252674 TI - Factors influencing the accuracy of the cardiac output monitoring and diagnostic unit for pneumatic artificial hearts. AB - The Cardiac Output Monitor and Diagnostic Unit (COMDU) has been the most widely used method to noninvasively determine cardiac output in pneumatic ventricles for the past 10 years. Clinical observation has suggested a discrepancy between the COMDU and expected cardiac outputs. In vivo tests verified and quantified this error. The error sources were examined using in vitro test conditions, with both the inflow and outflow, as well as COMDU flow readings, being analyzed. Transducer and calibration error sources were also identified, and the accuracy of the method for determining cardiac output for the in vitro test conditions was quantified. With a more accurate calibration scheme, the in vitro average error was reduced from -16.2% (range of 0.1% to -41.1%) to 0.1% (range 4.8% to -3.65). The major error sources were identified as missed inflow, transducer calibration and drift, and system variance. PMID- 2252675 TI - Ventricular assist device volume compensation using a two phase fluid. AB - A two-phase fluid (TPF) volume compensation chamber (VCC), using Freon as a working fluid, has been developed to reduce pressure fluctuations created in electric ventricular assist devices (VADs) during emptying and filling of the blood sac. The advantages of a TPF VCC over the currently employed flexible compliance chambers are as follows: 1) the TPF VCC has rigid external walls, eliminating the deleterious effects of fibrous ingrowth; 2) the internal diaphragm is made of Saran HB, which has a permeability two orders of magnitude less than that of butyl rubber; and 3) the TPF VCC has an external volume of 477 ml, comparable to that of the flexible compliance chambers used for electric VADs with a stroke volume of 100 ml. Experiments were conducted with the VCC attached to an electric VAD operated in a mock circulatory system. The results show that the strong temperature sensitivity of Freon vapor pressure does not compromise VAD flow output over a temperature range of 6 degrees C. Since body temperature generally fluctuates no more than 5 degrees C, this result is promising. A compromise is seen, however, in VAD power consumption. As the temperature of the VCC drops 6 degrees C, the mean pressure of the system drops 95 mmHg, causing an increase in power consumption that may require introduction of a temperature control system. PMID- 2252676 TI - Estimation of Reynolds stresses within the Penn State left ventricular assist device. AB - Fluid velocities were measured using a two-component laser Doppler anemometery (LDA) system at 129 locations within a Plexiglas model of a 70 cm3 Penn State electric Left Ventricular Assist Device (LVAD). The LVAD was driven by a pulsatile piston pump acting on an attached segmented polyurethane diaphragm. Bjork-Shiley tilting disc valves were used to provide unidirectional flow through the inlet and outlet ports. A seeded blood analog fluid, which matched the kinematic viscosity of blood at high shear rates and the refractive index of Plexiglas, was used to make the measurements. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The maximum Reynolds shear and normal stresses were calculated for each pump cycle time and location after filtering the data. The results reveal that the highest Reynolds shear and normal stresses occur in the near wall region just proximal to the aortic valve during diastole, and reach values of 5,300 dynes/cm2 and 10,800 dynes/cm2, respectively. The elevated turbulent stresses are observed during the period of regurgitant flow through the aortic valve, with peak stress values arising during the period of peak regurgitant flow. This supports the hypothesis that a regurgitant turbulent jet is formed near the wall of the prosthetic aortic valve and may be contributing to blood damage. PMID- 2252677 TI - A transcutaneous optical information transmission system for implantable motor driven artificial hearts. AB - Precise regulation of output voltage (motor voltage) and monitoring of the implanted pump were obtained with a transcutaneous energy transmission system. Information on both motor voltage and pump stroke is transmitted through the skin by frequency-modulated infrared pulses using a light emitting diode and a phototransistor. The motor voltage is compared with the nominal value, and the duty cycle of the primary pulse is regulated according to the error signal. Infrared pulses up to 100 KHz were transmitted through porcine muscle up to 1 cm thick. Both the pump stroke and motor voltage signals were transferred across the muscle without interference. The output voltage was kept almost constant for the change in tissue gap of 3-8 mm and of 0-10 mm in radial displacement. The system developed is useful for implantable artificial hearts. PMID- 2252678 TI - Rotacor: a new rotary blood pump. AB - A new rotary blood pump was tested in calves for 6 hr. The pump consists of a rigid housing with a trochoidal internal surface, an inlet and outlet, and two lateral walls. A two-corner piston rotates on an eccentric shaft in a trochoidal path, thus creating a gap seal. The pump is driven by a water-cooled DC motor. For right ventricular assist, a cannula was inserted into the right ventricle through the right atrium, and into the left ventricle for left ventricular assist. From a total of 10 experiments, two left ventricular assists, two right ventricular assists, and three biventricular assists were evaluated. The pump produced a pulsatile flow of 3 L at 70 rpm. Energy requirements were 2.19 watts for left, 2.06 for right, and 7.26 for biventricular assists. Plasma hemoglobin remained as low as 10 mg/dl during monoventricular, and increased during biventricular assists to 20 mg/dl after 3 hr, when it started to chop again; after 6 hr it was 16 mg/dl. From these preliminary results it is concluded that this new type of blood pump may be suitable as a circulatory assist device. PMID- 2252679 TI - Chronic in vivo evaluation of a portable electrohydraulic ventricular assist system with a linear actuator. AB - Chronic experiments of the electrohydraulic ventricular assist system with a linear motor actuator were performed in two goats weighing 54 kg and 56 kg, and the system was used for more than 30 days. The actuator was designed to be fixed on the goat's back with a saddle. The pump was connected between the left atrium and descending aorta and placed paracorporeally on the chest wall. Linear action of an actuator bellows was delivered by silicone oil in a U-shaped polyvinylchloride tube to activate the pump. The maximum output in the 56 kg goat was 5.0 L/min. Goats could stand and sit freely. The first goat with a pusher plate type pump died on the fifth day because of thromboembolism, but the second goat with a diaphragm type pump survived for 42 days. Blood chemistries remained within normal limits. Pump control was easy in both the duty-control mode and the stroke-control mode. With the automatic negative pressure control (ANPC) to prevent atrial wall sucking, the left atrial pressure was kept within +/- 10 mmHg, although left atrial pressure sometimes went below -80 mmHg without ANPC. Considering reliability, automaticity, and portability, the electrohydraulic ventricular assist system has become another choice for a practical, electrically driven ventricular assist system. PMID- 2252680 TI - Right-left ventricular balance in implanted electrically powered artificial hearts. AB - An electrohydraulic total artificial heart (EHTAH), using an interatrial shunt (IAS) for right-left heart balance, was evaluated in acute, in vivo, open-chested calves. The EHTAH system demonstrated physiologic autoregulation with Starling like responsiveness to preload. Output varied from 4 to 9 L/min, as right atrial pressure increased from 3 to 15 mmHg. Device output was minimally influenced by afterload. The efficacy of an IAS to balance the EHTAH was demonstrated over a wide range of preload and afterload conditions. Interatrial shunt flow rates, reflective of the degree of right-left imbalance, varied from 2% to 14% (IAS flow from left to right) of cardiac output. Left atrial pressures typically did not exceed right atrial pressures by more than 6-8 mmHg using an instrumented vascular graft such as the IAS. The simplicity and distinct anatomic, surgical, and engineering advantages of the IAS approach to right-left balance of implanted electrically powered artificial hearts justify further development toward a reliable long-term design. PMID- 2252681 TI - Development of an artificial extracellular matrix. Solution castable polymers with cell recognizable peptidyl side chain. AB - This article reports a novel cell-adhesion-promoting polymeric system as an adhesive-protein model. The characteristic features of the system are that polymers have recognition sites and are solution-castable on material surfaces. These co-polymers were prepared by radical co-polymerization of styrene with peptidyl macromer, which include an Arg-Gly-Asp (RGD) sequence, the minimal core peptide recognizable by cell adhesion receptors. Upon casting and subsequent immersion into water, RGD-peptide chains were enriched at the interface with water. Bovine endothelial cells (ECs) adhered to the cast surface, and adhesion was partly directed by RGD-recognition mechanisms. These co-polymers, incorporated with artificial bioactive ligands, may provide an artificial extracellular matrix (ECM) for implantable devices and hybrid organs using a conventional solution-casting technique. PMID- 2252683 TI - Improved biocompatibility by postfixation treatment of aldehyde fixed bovine pericardium. AB - Long-standing release of locally cytotoxic aldehyde concentrations is responsible for lack of spontaneous endothelialization and increased calcification of glutaraldehyde fixed bovine pericardium. Postfixation treatment with amino acids made in vitro endothelialization of bioprosthetic heart valves possible. Such treated pericardium calcified significantly less (13 +/- 4 micrograms/mg dry weight) than did conventionally processed pericardium (114 +/- 25 micrograms/mg) after 63 days of subcutaneous implantation in rats. To test the ability for spontaneous in vivo endothelialization, 5 sheep had 6 mm grafts made from postfixation treated pericardium (PTP) implanted into the carotid artery, compared to PTFE grafts on the contralateral side, which spontaneously endothelialize in animal models. In a pregnant animal, both grafts occluded. All remaining pericardial grafts remained patent, but one additional PTFE graft occluded and another one was stenosed. The area covered with red thrombus was significantly smaller in the PTP grafts (3.05 +/- 3.9%) than in the PTFE grafts 42 +/- 14% (p = 0.0036); TEM and SEM showed endothelial cells growing directly on the PTP, but only on myofibroblasts in PTFE grafts. Postfixation treatment of glutaraldehyde fixed pericardium aids spontaneous endothelialization and decreases tissue calcification. PMID- 2252682 TI - The effect of protamine on antibiotic action against Staphylococcus epidermidis biofilms. AB - Infection associated with medical devices may involve bacterial biofilms, a possible cause of antibiotic resistance. Protamine, a basic polypeptide, depresses the metabolic activity of Staphylococcus epidermidis in a standardized biofilm assay. The resistance of the biofilm preparations to many antibiotics, with the sole exception of rifampin, was confirmed. Rifampin produced predominant lysis and killing with foci of genetically programmed resistance. The combination of protamine with antibiotics produced no change, except the combination with rifampin where clear classic synergism with a totally bactericidal outcome was demonstrated. Protamine is a member of the larger family of charged polycations, some of which possess membrane potential altering properties, possibly interfering with the protective nature exhibited by the negatively charged bacterial biofilm matrix. PMID- 2252684 TI - Neointima formation on an antithrombogenic cardiac wall substitute that can be reconstructed by host cells. AB - The authors previously reported on a new cardiac wall substitute (collagen-coated ultrafine polyester mesh, CUFP), which in an animal study showed satisfactory antithrombogenicity due to its hydrophilicity and excellent neointimal formation because it induced cell migration and proliferation. Both the ultrafine polyester mesh, and the collagen cross-linked with a hydrophilic reagent, have a special affinity for host cells. In the current study, the focus was on neointima formation on the CUFP, compared with that on glutaraldehyde-treated equine pericardium (GA graft), over longer time periods. Twenty-one CUFPs, and 19 GA grafts as controls, were implanted as patches in the right ventricular outflow tract in 40 dogs. In the CUFP at 28 days, a thin neointima, which was almost endothelialized, had been formed. Fibroblasts and vasa vasorum were seen inside both the neointima and the graft wall. The CUFP showed a white, shiny, smooth, thin, and uniform neointima with endothilialization at 486 days, and the neointima was firmly anchored by day 699. In the GA graft at 484 days, however, the neointima was partly detached from the GA graft and almost no fibroblasts had infiltrated the graft wall. Therefore, neointimal formation on the CUFP is almost completed within 1 month and maintained over the long term. PMID- 2252685 TI - Biocompatible coatings with high albumin affinity. AB - A process was developed to coat complex medical devices with a thin, transparent, biocompatible film. The film is based on silicone rubber (SR) but has higher albumin affinity than SR. Two polymer forms have been developed: one substitutes hydroxyl groups (OH), the other, 16 carbon acyl groups (C16) in the siloxane side chains. Oxymercuration/demercuration or hydroboration reactions can be used. SEM reveals film surfaces are smooth, uniform, and featureless. ATR/FTIR spectra and advancing/receding water contact angle measurements confirm the presence of surface OH groups and suggest the presence of surface acyl groups. Albumin adsorption and retention are markedly enhanced for surface OH and C16 concentrations as low as 5% reaction yield. Kinetics, isotherm, and competitive albumin/fibrinogen adsorption studies suggest that surface hydroxylation, and perhaps C16 acylation as well, markedly improve the albumin affinity, but not the fibrinogen affinity, of this material. The SR film can be durably coated on several materials, making it possible to favorably treat many blood-contacting devices, using a simple immersion process. PMID- 2252686 TI - Backdiffusion rather than backfiltration enhances endotoxin transport through highly permeable dialysis membranes. AB - Endotoxin transfer from dialysate to blood by backfiltration has been reported to occur when highly permeable dialysis membranes available for efficient removal of beta-2-microglobulin are used clinically. Little is known concerning endotoxin transfer from dialysate to blood by diffusion. The present paper describes technical determination of diffusive and convective clearances for endotoxins based on conventional mass and momentum transfer models. Fractional diffusive transport of endotoxins with molecular weights of 1,000 and 10,000 daltons approximated unity. This indicates that clean-up of contaminated dialysate is necessary for safe hemodialysis treatment with highly permeable dialysis membranes. Diffusive in-flow of endotoxin with a molecular weight of 1,000 was calculated to be 278 and 88 pg/min for PAN-12CX2 and MC0.8H at an endotoxin concentration of inflowing dialysate of 2 pg/ml. These results demonstrate that dialysate should be carefully cleaned to prevent diffusive inflow of endotoxins from dialysate to blood. PMID- 2252687 TI - Leukocyte overshoot: a new sign of bioincompatibility in fast hemodialysis. AB - A high blood flow of 400 ml/min induces leukocytosis after 2 hr of dialysis with leukocyte concentrations of 110-150% of predialysis values. The leukocytosis occurs with both low and high biocompatible membranes, such as Cuprophan, Hemophan, and Polyamide. Cuprophan induces the most profound leukopenia, and also induces the most pronounced leukocytosis. For treatments with a given membrane there was, however, no correlation between leukopenia and leukocytosis. Leukopenia was independent of blood flow, while leukocytosis was strongly influenced by this factor. These observations indicate that different factors cause leukopenia and leukocytosis. Although a larger area induced more leukopenia, the effect was small. Membrane area had no effect on leukocytosis. There were no acute clinical side effects during dialysis that could be related to the leukocyte overshoot. The cause and chronic clinical consequences of leukocyte overshoot are unknown. PMID- 2252689 TI - Low-dose heparinization can be used with DEAE-cellulose hemodialysis membranes. AB - The ability of DEAE-cellulose (Hemophan) membranes to bind heparin may reduce bioavailable heparin and predispose to dialyzer clotting, thus preventing use of Hemophan with low-dose heparin. To examine this possibility, residual blood volumes were determined following 95 treatments with dialyzers containing Hemophan membranes in 11 patients. No heparin was added to the saline used to prime the dialyzers. The anticoagulant effect of heparin was measured using recalcified activated clotting times (RACT). Two heparin doses, calculated by a pharmacokinetic model to increase baseline RACT by 12.5% and 25%, were used for each patient. The mean heparin loading doses were 10.2 +/- 2.8 and 15.3 +/- 2.2 IU/kg, respectively, and the mean infusion rates were 11.1 +/- 3.2 and 14.7 +/- 3.2 IU/kg/h, respectively. Residual blood volumes were determined by red cell lysis and hemoglobinometry. In 88 treatments, residual blood volume averaged 1.6 +/- 1.5 ml. In the other seven treatments, residual blood volume greater than 10 ml was seen. In five of these cases, clotting appeared to propagate from the arterial drip chamber. Residual blood volume did not correlate with the level of heparin. The data show that low-dose heparin can be used with Hemophan membranes, and suggest that blood tubing design may be an important factor in blood circuit clotting during hemodialysis. PMID- 2252688 TI - Sterile versus non-sterile dialysis fluid in chronic hemodialysis treatment. AB - As the quality of water in the dialysis fluid varies considerably, and in view of the fact that endotoxin or active derivatives can cause acute side effects in patients, the dialysis fluid must be sterile. Therefore, we introduced ultrafiltration of dialysis fluid before entering the dialyzer. Fifteen patients, (ten women, five men) were treated for 4 weeks with nonsterile, and then with sterile dialysis fluid. The bacterial loading in the dialysis fluid before hemodialysis was 1.34 X 10(5)/ml, and after hemodialysis 2.9 X 10(3)/ml; the endotoxin concentration was high and varied between less than 1 EU/ml and greater than 10 EU/ml before and after hemodialysis. After ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane, all samples were free of bacteria and the concentration of endotoxin was lower than the detectable limit (less than 0.03 and less than 0.5 EU/ml). With ultrafiltration of dialysis fluid we can obtain sterile dialysate, which is endotoxin free. Interleukin-1 and tumor necrosis factor in the patients with ultrafiltration was significantly lower than without ultrafiltration. PMID- 2252690 TI - Ionic strength affects diffusive permeability to an inorganic phosphate ion of negatively charged dialysis membranes. AB - Electrolytes undergo electrostatic resistances in reaching membrane surfaces and passing through membrane pores when weakly charged dialysis membranes are used in hemodialysis treatments. Diffusive permeability to an electrolyte of weakly charged dialysis membranes depends upon the effective charge density of the membranes, which varies with ionic strength. The authors carried out dialysis experiments at a temperature of 310 K, with 32P-Na2HPO4 in aqueous NaCl and bovine serum, to obtain diffusive permeability to an inorganic phosphate ion of regenerated cellulose, and polymethylmethacrylate membranes of various fixed charge densities at varying ionic strengths ranging from 1.66 to 100 mol/m3. Diffusive permeability to an inorganic phosphate ion increased with ionic strength. Bovine serum, having an ionic strength of approximately 150 mol/m3, gave higher diffusive permeability to an inorganic phosphate ion. The internal structure of dialysis membranes, such as pore size, surface porosity, and tortuosity, also affects diffusive permeability. The electrolyte diffusion theory gives an effective charge density of -5.3 mol/m3 for the cellulosic membrane. In conclusion, ionic strength enhances diffusive permeability to an inorganic phosphate ion in both aqueous NaCl and bovine serum. Inorganic phosphate ion transport through negatively charged dialysis membranes depends upon the degree of dissociation of inorganic phosphate, the molecular size and valence of hydrated inorganic phosphate ion, the effective charge density and internal structure of the membrane, and ionic strength. PMID- 2252691 TI - In vivo rheologic effects of lipid apheresis techniques: comparison of dextran sulfate LDL adsorption and heparin induced LDL precipitation. AB - The effects of two different LDL apheresis techniques, heparin-induced LDL precipitation (HELP) and dextran sulfate LDL adsorption (DSA), were compared in six patients with familial hypercholesterolemia. Total and LDL cholesterol were effectively lowered with both techniques. The reduction of serum triglycerides was more pronounced with DSA, whereas the reduction of HDL cholesterol was more pronounced with HELP. Single sessions using both techniques immediately reduced whole blood and plasma viscosity, as well as erythrocyte aggregation. Serum fibrinogen decreased by 62% (HELP) and 11% (DSA). Maintenance lipid apheresis administered 1 time per week resulted in a sustained reduction of total and LDL cholesterol and was associated with a sustained improvement in blood flow properties. Data suggest that besides serum fibrinogen, serum lipoproteins may adversely effect the rheologic characteristics of blood. PMID- 2252692 TI - (A)typical symptoms during single needle dialysis. AB - In 5 elderly patients, an abnormally high occurrence of some symptoms was noted during dialysis. All patients were dialyzed with biocompatible membranes, bicarbonate dialysate, and a blood flow of 250 to 300 ml/min by a single needle system, on a fistula 14 Gauge catheter-needle. These symptoms were: 1) "angina," resistant to O2 and nitrates, with biochemical stigmata of infarction, but without electrocardiogram (ECG) localization; 2) intractable persistent hypotension, not hypovolemic, lasting 1 or 2 days; 3) esophagal spasms, with inability to swallow solid food. Because we knew that these symptoms were compatible with hemolysis (biochemically proven by the increase in serum LDH during dialysis and by a fall in haptoglobin) due to red cell fragmentation (RCF), we switched these patients from fistula dialysis (A) to central catheter dialysis (B), with the same apperture, blood flow, etc. The total number of sessions of A versus B were 512 and 891; the mean LDH ratios (serum LDH postdialysis divided by predialysis) were 1.8 and 1.0 (= no RCF); angina events were 132 (26%) for A, and 25 (3%) for B; persistent hypotension was seen 37 (7%) times in A and 5 (0.6%) times in B; esophagal spasms were noted 65 (13%) times for A, and 0 times for B. This clinical improvement was so overwhelming that 3 patients refused to be dialyzed again using their well functioning fistulae. This study also proved the need for a better designed and manufactured peripheral dialysis catheter-needle. PMID- 2252693 TI - Acellular matrix allograft small caliber vascular prostheses. AB - We have developed an acellular matrix vascular prosthesis (AMVP) made by detergent and enzymatic extraction of natural arteries, yielding a tissue framework of collagen and elastin from the original vessel, with preservation of the natural basement membrane at the blood flow surface. These biografts have excellent handling characteristics and suturability, as well as low thromboreactivity. Whole vessel static testing of circumferential compliance (8.9 +/- 1 [SEM] X 10(-2)% mmHg at 100 mmHg) revealed behavior virtually identical to the paired natural vessel from which each AMVP was derived in nine canine carotid arteries. We implanted 16 canine-origin AMVPs into nine dogs (12 femoral and three carotid arteries, and one infrarenal aorta) with no antithrombotic drugs. Angiographic patency was maintained in 15 of 16 (one occlusion within 3 days) for follow-up from 3 days to 6 years, with no aneurysm formation in three AMVP at over 4 1/2 years. Explant analysis revealed preservation of AMVP elastica and collagen with no inflammation or dystropic calcification of the AMVP, and almost total thrombus free flow surfaces. These results suggest that allograft AMVPs could achieve long-term patency equivalent to saphenous veins. PMID- 2252694 TI - Development of a soft, pliable, slow heparin release venous graft. AB - To prevent their collapse, a certain amount of stiffness is generally required for prosthetic venous grafts, so EPTFE grafts have been used. However, the native vein is pliable without any stiffness. We developed a soft and pliable graft that can maintain patency of the lumen because of its compliance. Fresh porcine ureter was incubated in a ficin solution to remove cell components and noncollagenous proteins. One percent protamine sulfate solution was injected into the ureter lumen to impregnate the inner surface. The ureter was then crosslinked with a 1% glutaraldehyde solution, dipped into a 1% heparin solution for 5 hours, and rinsed with distilled water. This procedure made the ureter very soft and pliable, and also conferred antithrombogenicity to the graft by heparinization. The grafts were implanted into the posterior vena cavae of 20 dogs and were removed from 1 to 878 days after implantation. Eighteen grafts were patent, but two grafts were occluded at the anastomotic site at 218 and 107 days, respectively. As a control experiment, nonheparinized grafts were implanted into 15 dogs; all were occluded with fresh thrombi. All the patent grafts kept their original elasticity, which allowed them to heave in unison with the heartbeat, and were similar in appearance to the native vena cava. Heparinization was effective in preventing thrombus formation. These results indicate that this type of graft is an ideal prosthesis as a venous graft, having physiologic properties such as compliance and antithrombogenicity. PMID- 2252695 TI - Endothelialization of vascular prostheses by transplantation of venous tissue fragments. AB - A method to accelerate the endothelialization of vascular prostheses by seeding venous tissue fragments was developed. A piece of peripheral vein was obtained, chopped into small fragments, and stirred into 20 ml of saline, making a tissue suspension. This suspension was sieved through the wall of a highly porous vascular prosthesis (water porosity: 3,600-4,000). The prostheses, (7 mm ID and 5.7 cm in length) seeded with tissue fragments, were implanted into the thoracic descending aortae of 20 dogs, and were removed from 1 to 371 days after implantation. Ten prostheses, preclotted with fresh blood, were used as controls. In the seeded grafts, an infinite number of endothelial cells migrated and proliferated from the fragments. These had produced numerous capillaries by 5 days after implantation that had reached and opened onto the luminal surface of the prosthesis. From these openings, numerous endothelial cells spread out and formed colonies. With the increase in the size of the colonies, the inner surface was completely endothelialized within 5 weeks. This quick neointimal formation by seeding venous tissue fragments might be applicable to several artificial organs. PMID- 2252696 TI - Development of a polyurethane percutaneous access device for long-term vascular access. AB - The percutaneous placement of intravascular devices creates a portal for microbial invasion that can result in local infections or septicemia. In nature, resistance to "exist site" infection in percutaneous organs, such as teeth, is prevented by a dense collagen/epithelial barrier. A new percutaneous access device has been developed that incorporates a porous polyurethane "button" at the subdermal level. This device promotes the development of a collagen/epithelial interface, thus inhibiting sinus formation. Twelve percutaneous access devices (PCADS) were implanted in calves; eight devices were utilized for venting of, and hard wire passage to, an implantable left ventricular assist device (LVAD) and served as controls. Four devices were utilized for long-term vascular access. The PCADS remained in situ for 2-127 days (mean 70). Excellent healing was apparent in all cases, and no exit site or catheter related infections occurred. Histologic examination demonstrated fibroblastic in-growth and collagen deposition within the porous polyurethane, which provides a barrier to epithelial migration and firmly anchors the device. These PCADS appear to reduce exit site infections and may improve upon currently available long-term vascular access catheters. PMID- 2252697 TI - Events following implantation of an intraluminal ringed prosthesis in the ascending, transverse, and descending thoracic aorta. AB - From March 1978 through July 1985, 23 patients underwent implantation of 24 intraluminal ringed prostheses (IRP). There were 18 men and 5 women, with a mean age of 54.7 years, range 15-74 years. Eleven IRP were placed in the ascending aorta, two in the transverse arch, and 11 in the descending aorta. Pathology included acute aortic dissection in four patients, chronic dissection in four, and aortic aneurysm in 16. There were eight hospital deaths (35%). Causes of death included acute cardiac failure in seven patients, and ruptured abdominal aortic aneurysm in one. IRP complications requiring revision included right coronary artery occlusion in three of 11 patients (27%) with an IRP in the ascending aorta. Graft revision was also required in three of 11 IRP implanted in the descending aorta (27%), due to graft occlusion in one and graft stenosis in two. Of the six patients with IRP complications, there were three hospital deaths (50%). All 15 hospital survivors were followed for a mean of 68.5 months, range 5 112 months. There were four late deaths (26.7%). Causes of late death included hemoptysis in one, cardiomyopathy in one, and aortic redissection and rupture in two. We conclude that patients undergoing repair of aortic pathology with IRP have an important risk of early phase events, as technical problems can occur due to malposition and slippage of the securing rings. PMID- 2252698 TI - In vitro and in vivo testing of a new valved intravascular catheter design. AB - Long-term intravascular catheterization carries a finite risk of catheter occlusion. A catheter tip valve design is presented (Buchwald-Wigness, Strato Medical Corporation, Beverly, MA) which incorporates features designed to decrease the risk of thromboembolism and reduce the need for maintenance procedures. Aspiration and infusion are controlled by separate valves, making it possible to engineer optimized inlet and outlet parameters. The outlet valve is an elastic sleeve expanded around the sidewall outlet ports which opens under injection pressure. The inlet valve is a tubular elastic element compressed against the inlet port from within the lumen, opening under aspiration pressure. A series of valves were prototyped with outlet pressures ranging from 2 to 100" H2O, and inlet pressures ranging from -40-70" H2O, and flowrates at 36" H2O of greater than 1,400 ml/hr. Dog implants of two prototypes with outlet valve pressures of 10" H2O, and inlet pressures of -40" H2O, demonstrated that dormant periods of up to 7.5 weeks could be achieved without detectable blood cell entry into the lumen. No significant hemolysis was observed in blood samples aspirated with a 6 cc syringe (8% scored "slightly hemolyzed" vs. 44% with the nonvalved controls) indicating that a hemodialysis application is likely. PMID- 2252699 TI - An on-line monitor of dialyzer Na and K flux in hemodialysis. AB - A closed loop Na kinetic model is developed which permits 1) prescription of precise profiles of Na removal from its extracellular volume of distribution ((dVeCe)/dt), while 2) assuring that the total interdialytic accumulation of Na is removed during each dialysis. The model requires precise continuous measurement of Na flux in the dialysate stream, and a device to accomplish this (Ionflow) was developed and evaluated. In vivo studies showed that changes in body content of Na agreed to +/- 40 mEq, with total Na flux measured by Ionoflow. This agreement is excellent, considering that +/- 1 mEq/L in blood Na represents approximately 40 mEq in the average patient. The Ionoflow is considered accurate to +/- 10 to 20 mEq Na over a dialysis. The Ionoflow fulfills monitoring requirements necessary to implement clinical trials of closed loop Na modeling. PMID- 2252700 TI - Rapid methods of estimating Kt/V: three formulas compared. AB - Three rapid formulas for Kt/V were compared: 1) Kt/V-PRU = 0.04*PRU-1.2; 2) Kt/V PRUopt = 0.026*PRU-0.46; and 3) KTV-LN = -In(R-0.03-UF/W). Accuracy was compared in a database of 339 3/week modeling sessions in 256 patients. The standard of comparison was Kt/V obtained by 3 point variable volume single pool modeling, using K values estimated from KoA, Qb, Qd, and UF rate. The most accurate formula was Kt/V-LN, which correlated with Kt/V to a high degree (0.994), and with a [%ERROR] of only 2.2 +/- 1.7 (SD). There was no correlation of %ERROR with the modeled Kt/V. The least accurate formula was Kt/V-PRU. Although the correlation of Kt/V-PRU with modeled Kt/V was high (0.962), the [%ERROR] was 12.0 +/- 11, and %ERROR correlated significantly with modeled Kt/V (0.68). The Kt/V-PRUopt showed a high correlation with modeled Kt/V (0.962), and a [%ERROR] of 5.0 +/- 3.8; the latter had a minimal correlation with modeled Kt/V (-0.168). The relative accuracies of the three formulae were: Kt/V-LN vs. Kt/V-PRU = 5.98, Kt/V-LN vs. Kt/V-PRUopt = 2.45. The results suggest that Kt/V-LN is a more accurate estimate of Kt/V than any formula based on PRU alone. PMID- 2252701 TI - Various methods for calculation of Kt/V: a clinical comparison. AB - Analysis of the National Cooperative Dialysis Study (NCDS) showed that dialysis morbidity and mortality was related to Kt/V of urea. Various formulas have been derived to make calculation of Kt/V simpler. We compared the kinetically measured Kt/V (A) to estimated Kt/V derived from approximate total body water (0.6 body weight) and uniform dialyzer clearance (B), Kt/V = 0.04 PRU-1.2 where PRU is % reduction in BUN (C) and Kt/V = In(R-0.03-UF/W) where R is post/pre BUN, UF is ultrafiltration L/HD and W is postdialysis weight (D) in 26 patients. The correlation coefficient (r) was 0.14 (p less than 0.05) for A vs. B; 0.75 (p less than 0.01) A vs. C; 0.77 (p less than 0.01) A vs. D; and 0.97 for C vs. D. In an additional 51 patients, Kt/V was calculated using formulas B, C, and D. The r was 0.91 C vs. D, 0.70 B vs. D, and 0.68 B vs. C. With B, greater than 30% of the patients could have been misclassified using NCDS criteria for adequacy of dialysis. The study suggests that use of formulas C and D, but not B, is appropriate and accurate for Kt/V calculation. Formula C may be simpler and easier than D, as UF and W are not required. Serial Kt/V could be easily and accurately calculated using C and D for quality assurance and quantitation of dialysis. PMID- 2252702 TI - A muscle powered cardiac assist device for right ventricular support: total assist or partial assist? AB - A muscle powered cardiac assist device (MCAD) for right ventricular support requires optimized diastolic filling to obtain full stroke and acceptable fluid dynamics. A valved and spring-assembled skeletal muscle ventricle (SMV) was designed as a prototype MCAD, regardless of fluid dynamics. The present study addresses the optimal bypass method for right ventricular support, and predicts the future design for an implantable MCAD. Latissimus dorsi muscle (LDM) of 11 dogs were conditioned electrically for a one year maximum, and transformed into fatigue-resistant muscles (Type I fibers). Superior and inferior vena cavae were anastomosed using one arm of a Y-shaped vascular graft, as an inflow conduit, and the outflow conduit was placed on the main pulmonary artery. SMV was wrapped with transformed LDM and the bypass method was varied by SVC and/or IVC ligation. SMV demonstrated sufficient right ventricular support on total bypass (70% compared with control output), and the maximum pump off-to-on flow ratio (200%) was obtained. Maximum SMV power output was 0.27 X 10(6) erg, which was equivalent to that of canine right ventricle. Right atrial-to-pulmonary artery bypass was also constructed by using SMV in another 14 dogs, and also showed that total bypass was preferable for optimal SMV diastolic filling. In conclusion, specific requirements for a future MCAD include a subsystem assembly such as a spring, magnet, or alternative auxiliary muscle pump assembly for MCAD filling, and total bypass with optimized fluid dynamics and anatomic fitting. PMID- 2252703 TI - In vitro and in vivo evaluation of a right ventricular assist device. AB - A simple right ventricular assist device (RVAD) has been developed. This device will be useful in situations where biventricular failure has been partially treated by placement of a left ventricular assist device, or when right ventricular failure occurs in isolation. This pneumatically actuated, R-wave synchronized, sac type pump contains no valves, and is connected by a graft to the pulmonary artery. The RVAD was tested in a circulation simulator to verify its hemodynamic efficacy and then implanted in six calves for 2-4 weeks to evaluate its biocompatibility. In vitro testing of the RVAD demonstrated that it restored normal hemodynamics in the presence of severe simulated RVF. In six animal implantations, a small amount of thrombus was found in one pump. No anticoagulants were employed. Thrombus was present in the connecting graft in three animals; in two this was clearly related to technical implant errors. No evidence of significant hemolysis was found. This simple RVAD has been found to be hemodynamically effective, is simple to use, and is well tolerated. Refinements in the interconnection graft between the pulmonary artery and the device are necessary. PMID- 2252704 TI - Functional heart replacement with the spindle pump: first results. AB - The spindle pump is a nonpulsatile blood pump with a double function, i.e., it works centrifugally and represses simultaneously. The first experiences with this type of pump used as a biventricular assist device in four short-term animal experiments (up to 13 hours) are described. It can be demonstrated that in cases of a normally beating heart, this BVAD decompresses both ventricles by 60-70%, while the aortic pressure is slightly increased; on the other hand, in case of ventricular fibrillation, the BVAD with two spindle pumps maintained the entire circulation, at an arterial pressure between 80 and 90 mmHg with a flow volume between 3.5 and 4 L/min. PMID- 2252705 TI - Pulmonary artery counterpulsation with a skeletal muscle power source. AB - We evaluated the feasibility of using skeletal muscle (SM) to provide pulmonary artery (PA) counterpulsation in an acute pulmonary hypertension (PHT) model. PA counterpulsation was achieved in six dogs with a dual chambered pump powered by the latissimus dorsi muscle. A rate-responsive stimulator was used to make the muscle contract in counterpulsation. Graded PHT was induced by infusing 150 microns glass beads into the PA, while RV and PA pressures were monitored. With PA pressures ranging from 19/10 to 115/62 mmHg, effective counterpulsation was observed. The degree of counterpulsation was influenced by the extent of PHT induced, with the amount of RV tension-time index (TTI) unloading correlated with the level of PA systole (r = 0.92). Therefore, results were divided into two groups (Group 1: PA systole less than or equal to 40 mmHg, and Group 2: PA systole greater than 40 mmHg). In Group 1, RV TTI decreased from 11.29 +/- 0.76 to 9.99 +/- 0.72 mmHg.sec, PA diastole increased from 20 +/- 2.3 to 31 +/- 3.0 mmHg, and PA mean increased from 24 +/- 2.2 to 2.9 +/- 2.2 mmHg (all p less than 0.05). In Group 2, RV TT1 decreased from 15.12 +/- 1.83 to 10.99 +/- 0.90 mmHg.sec, PA diastole increased from 41 +/- 3.5 to 64 +/- 6.2 mmHg, and PA mean increased from 49 +/- 4.8 to 55 +/- 5.7 mmHg (all p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252706 TI - Novacor left ventricular assist filling and ejection in the presence of device complications. AB - In order to better understand the relationship among certain device related complications and Novacor left ventricular assist system (LVAS) pumping parameters, a Mock Circulatory Loop was utilized to simulate the following clinically realistic conditions: 1) inflow valve regurgitation, 2) inflow cannula obstruction, 3) outflow valve regurgitation, and 4) outflow cannula obstruction. Various pumping parameters (e.g., pump rate, stroke volume, pump output) were recorded at baseline (control) and during each simulation. Additionally, pump volumes were continuously recorded and differentiated for calculation of rates of pump filling (FR) and ejection (ER). The results indicate that perfusion pressures and rates of filling and ejection change significantly in the presence of device complications. The implications of these findings, as relates to assessment of pump operation in LVAS patients, are discussed. PMID- 2252707 TI - Efficacy of a biomechanical counterpulsation device powered by skeletal muscle for right heart assist. AB - A valveless, single-orifice counterpulsation device powered by skeletal muscle was applied to the pulmonary artery for right heart assist. Latissimus dorsi muscles of six dogs had been electrically conditioned for four months in advance (Group 1); the muscles of eight dogs were not preconditioned (Group 2). A polyvinyl chloride balloon was placed beneath the latissimus dorsi muscle and connected to the left pulmonary artery using a noncollapsing graft. Latissimus dorsi muscle was paced synchronously to the cardiac cycle to produce pulmonary artery diastolic augmentation. Percent changes in diastolic augmentation pressure (% DAP) in the main PA was measured. Percent DAP after 180 min assistance was 91 +/- 10% in Group 1, whereas it decreased to 17 +/- 12% in Group 2 (p less than 0.001). These results demonstrate that electrically conditioned skeletal muscle is effective as a power source in right heart assist. PMID- 2252708 TI - An intrathoracic left ventricular assist system: utilization of results from a development program. AB - An intrathoracic, electrohydraulically actuated, left ventricular assist system (LVAS) was subjected to formal device readiness testing. Endurance testing was initiated on eight systems before testing was halted due to failure of four of the systems. Three failed due to environmental leakage. Solutions were straightforward, involving gasket changes and o-ring resizing. The fourth failure involved a magnetic coupling piston swelling and seizing. The failure was attributed, after long investigation, to hydrogen adsorption by the samarium cobalt magnets. An unknown number of coupling magnets were affected in this fashion, necessitating complete replacement of magnets to resolve the problem. However, this was beyond the scope of the program, and no further endurance testing was accomplished. The test experience of the Nimbus/CCF LVAS has demonstrated all functional aspects of the complete LVAS, both in vitro and in vivo, and the endurance and reliability potential is indicated as well. Although the LVAS program is currently inactive, its legacy of technical innovations continue to drive the development of other medical devices. PMID- 2252709 TI - Maintenance of circulation during ventricular fibrillation with the simultaneous use of two "counterpulsation" devices. AB - Two valveless, single orifice counterpulsation devices, with pumping stroke volumes of 65 ml each, were implanted on the ascending aorta and pulmonary artery of seven open chest anesthetized dogs. After completion of the preparation, ventricular fibrillation was induced. The devices were synchronized to pump simultaneously at a rate of 85-100 bpm. The combined use of the counterpulsation devices provided maximal aortic pressure of 111.4 +/- 25.1 mmHg during ventricular fibrillation for a period of 15-60 min. The mean left ventricular pressure was 17.7 +/- 4.4 mmHg, and the cardiac index 64.5 +/- 23.6 ml/kg/min. Cardioversion of ventricular fibrillation to sinus rhythm restored normal hemodynamics. The counterpulsation device implanted on the ascending aorta was not able to maintain circulation for more than 5 min after the induction of ventricular fibrillation, if used alone. In conclusion, the use of two counterpulsation devices implanted on the ascending aorta and pulmonary artery was able to maintain circulation in experimental animals during ventricular fibrillation. PMID- 2252710 TI - Limitation of myocardial infarct size by a right ventricular assist device. AB - To evaluate the effects of an RVAD on myocardial ischemic injury during right coronary artery (RCA) ligation, a pneumatically driven pusher plate pump was inserted between the right atrium and pulmonary artery, and the RCA was ligated at its origin for two hr. There were 18 sheep, of which nine each served as the control and RVAD groups. Hemodynamic parameters and blood samples were collected from the coronary sinus. Area at risk and area of infarct were detected by gentian violet injection and triphenyltetrazolium (TTC) staining. Hemodynamic parameters (left ventricular systolic pressure (LVSP), cardiac output (CO], and creatine kinase levels in coronary sinus blood tended to be beneficial, to some degree, in the RVAD group. Electron microscopic examination revealed chromatin clumping and mitochondrial destruction, however this ultrastructural damage was more severe in the control group. The ratio of area of infarct to area at risk in the RVAD group was significantly less than that in the control group, being 20.25 +/- 6.93% vs. 47.24 +/- 10.53% (p less than 0.05). The infarct size induced by RCA occlusion was significantly reduced by the RVAD, due to the right ventricular unloading via reduced myocardial oxygen demand. PMID- 2252711 TI - A novel mechanical cardiac assist device for reversing left ventricular failure. AB - Diastolic augmentation of aortic pressure is an efficacious means of improving coronary perfusion in heart failure. A novel mechanical cardiac assist device (MCAD), that has advantages over a conventional intraaortic balloon pump and left ventricular assist devices, has been developed. It consists of a high efficiency rotary solenoid, coupled to a pair of actuator plates that clamp on a shunt aortic graft section, and operates in a diastolic counterpulsation mode. The system has been evaluated in six anesthetized, thoracotomized dogs with myocardial ischemia. The MCAD was activated 30-40 min after coronary artery occlusion and synchronized with the R-wave. As illustrated by a representative sample of the data obtained from one of several trials, the preliminary experimental results demonstrated that the MCAD worked effectively to fulfill the primary functions of a counterpulsation assist device, i.e., augmentation of coronary perfusion and reduction in the vascular impedance to ventricular ejection. PMID- 2252712 TI - Mechanical properties of basal and marginal mitral valve chordae tendineae. AB - The authors determined the stress/strain characteristics of basal and marginal mitral valve chordae tendineae. The chordae exhibit a nonlinear stress/strain behavior typical of biologic materials, with a discrete transition in the tensile elastic modulus. The post-transition moduli for both basal and marginal chordae are greater than the pretransition values by a factor of approximately 10. In addition, the stress carried by the marginal chordae is higher than that supported by the basal ones at all recorded strains, indicating the marginal chordae are stiffer than the basal chordae. The authors determined the number and distribution of chordal insertions, and found a marginal to basal insertion ratio of almost 2 to 1. The implication is that it may be possible surgically to remove basal chordae without seriously compromising mitral valve function. PMID- 2252713 TI - Long-term efficacy of Al3+ for prevention of bioprosthetic heart valve calcification. AB - AI3+ preincubation has been shown in 21 and 60 day implants to inhibit calcification of glutaraldehyde preserved bovine pericardium (GPBP) in the rat subdermal model. This study was designed to assess the long-term anticalcification efficacy of GPBP AI3+ preincubation. Rat (50-60 gm, male, CD Sprague-Dawley) subdermal implants of GPBP, pretreated with 0.01 M or 0.1 M AICI3, were carried out for 21, 60, 90, and 120 days. Each explanted GPBP was analyzed for Ca2+ by atomic absorption spectroscopy and for AI3+ by atomic absorption spectroscopy or neutron activation irradiation. Results showed profound long-term (implant duration 120 days) inhibition of calcification after GPBP preincubation in 0.1 M AICI3 (Ca2+ = 21.8 +/- 12.6 micrograms/mg), compared to control (Ca2+ = 329.0 +/- 20.3 micrograms/mg). After preincubation in 0.1 M AICI3 and 21 day rat subdermal implantation, GPBP AI3+ levels declined from 9033 +/- 680 micrograms/g (control = 6.3 +/- 3.7 micrograms/g) to 2700 +/- 156 micrograms/g; however, there was no further significant decline in GPBP AI3+ levels after long-term implantation of 120 days (2618.4 +/- 349 micrograms/g). The authors conclude that GPBP preincubation in 0.1 M AICI3 markedly inhibited pathologic calcification to 7% of control values in the rat model after long-term (120 day) subdermal implantation. PMID- 2252714 TI - A new bioprosthetic cardiac valve with reduced calcification. AB - A bioprosthetic cardiac valve cross-linked with a glycerol polyglycidyl ether polyepoxy compound (PC) was developed in order to reduce calcification and degeneration, which often occurs in bioprosthetic cardiac valves. Aortic valves harvested from dogs were treated with PC (PC valve). Right ventricle (RV) pulmonary artery (PA) bypasses were placed in 12 dogs with PC-valved conduits, and the main PA was ligated. X-ray right ventriculography at 36 days (1 dog) and 37 days (1 dog) revealed an excellent open/close performance of the PC valve, and there was no visible thrombus in the valve. In our basic study, PC treated collagen gel disks implanted in the subcutaneous layer of growing rats showed remarkably less calcium deposition than did those treated with glutaraldehyde (GA). Biologic materials cross-linked with PC maintain their pliability, and become more hydrophilic and more hydrated than those cross-linked with GA. The hydrophilicity and hydration provide sufficient antithrombogenicity and a suitable environment for metabolism in the tissue fluid which contains oxygen, nutritive substances, and electrolytes, leading to inhibition of material degeneration. Therefore, PC valves are expected to show good valve function, sufficient antithrombogenicity, and excellent durability with less calcification, when compared to GA treated valves. PMID- 2252715 TI - Detailed examination of complete bioprosthetic heart valves. AB - Six (3 control and 3 explanted) bioprostheses were examined histologically after embedding the complete valve in "plastic" and sectioning across the valve at 90 degree to the horizontal plane, and then horizontally across a stent post, with a low speed saw. The prostheses, porcine or pericardial, had been in place 52 to 121 months. In addition to cusp changes of degeneration and calcification that have been previously reported, the authors found extensive pannus deposition on the cloth covering the inflow surface of the prostheses, with some extension onto the biologic components; evidence of insudation of tissue fluid and ingrowth of fibroblasts; deposition of collagen; and infiltration of mononuclear cells in the interstices and interfaces. Non-biologic components showed changes which may have affected prosthesis function. The synthetic material covering the metal/plastic frame showed interstitial mononuclear cells. Two of the three explanted valves showed changes in the polymeric plastic, and one in the metal components, including accentuated notching along the surfaces when compared to unimplanted prostheses. A larger number of prostheses must be examined before definite conclusions can be drawn. PMID- 2252716 TI - Delrin as an occluder material. AB - Delrin (DR) has been used in biomedical applications for more than 25 years. Because of durability concerns, it was replaced by the expensive Pyrolytic Carbon (PC) in numerous cardiac valves. However, the durability problem could be related to design rather than poor materials selection. Recent reports on brittle fracture of PC, leading to sudden deaths, have prompted a critical comparison between DR and PC in the St. Vincents Mechanical (SVM) heart valves. Three SVM-DR and SVM-PC valves were subjected to accelerated life cycle tests, and examined for wear at 400 million cycles. These results were compared to those of Bjork Shiley Delrin (BS-DR) valves. Wear in BS-DR valves in vivo for more than 17 years were also analyzed and compared. Using a linear (wear depth)-log (cycles) plot, wear rates in mm/log (million cycles) were obtained. The results showed that the wear rates for DR and PC in SVM valves are close. The double reduction in wear rate of the SVM-DR, compared to BS-DR, is probably due to the lower contact stresses of the SVM valves. SVM-DR in vivo should, therefore, have lower wear. The PC discs also showed edge chipping and hairline cracks. The authors conclude that the durability of DR can be improved by design and, since it is more impact resistant than PC, it is a safer, more inexpensive occluder material for cardiac valves. PMID- 2252717 TI - An electromagnetically controllable heart valve suitable for chronic implantation. AB - A controllable valve suitable for chronic implantation was designed, and preliminary performance tests were conducted. A Bjork-Shiley monostrut valve with an 18 mm disk was modified so that permanent magnetic material was implanted in the disk and an electromagnet was fitted around the ring of the valve. The opening of the disk is controlled by the interaction of the magnetic field created by the permanent magnets, and the field created by the electromagnet. The coil can be activated intermittently so that the valve can be held in the closed position or allowed to open and close unimpeded. The unit was designed to hold a maximum hydrostatic pressure equivalent to 50 mmHg. Power consumption by the prototype, while holding a pressure of 50 mmHg, is less than 10 watts. The overall diameter of the valve and electromagnet is 27 mm. The design and test results indicate that it is feasible to develop a unit suitable for chronic implantation in experimental animals and, possibly, in prosthetic blood pumping devices. PMID- 2252718 TI - Effect of a pulsing electromagnetic field on metabolically derived osteoporosis in rats: a pilot study. AB - The literature suggests that a pulsating electromagnetic field (PEMF) is effective against bone loss in disuse osteoporosis. This study was conducted to evaluate the effects of PEMF on metabolically derived osteoporosis in rats. Sixteen 5 month old female Sprague-Dawley rats were divided into three groups (G 1,2,3). G-1 was given a normal diet and no exposure to PEMF; G-2,3 were oophrectomized and fed a low calcium diet for 8 months; and G-3 was also exposed for 24 hr/day to PEMF generated by applying a 15 Hz, 5.6 A peak to peak square wave to Helmholtz coils (64 cm I.D., 200 turns/coil). The rats were sacrificed at 4, 6, and 8 months. Skeletal changes were analyzed by measurements of acid extracted bone calcium and bone mineral content (BMC) using single photon absorptiometry (SPA). Although all animals started at approximately the same weight (mean of 290.0 g), G-2 showed a more progressive increase. While the mean weight after 8 months in G-1 was 350.0 g, and 352.5 g for G-3, that in G-2 was 400.0 g. The calcium content of the femur in G-2 and G-3 at 8 months was lower than that of G-1, but there were no significant differences among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252719 TI - Experimental development of a fixed volume, gravity draining, prosthetic urinary bladder. AB - A fixed volume, semi-rigid, gravity draining prosthetic urinary bladder has been developed in experimental animals. The conceptual model demands: 1) an encrustation resistant lumenal surface; 2) successful urothelial-prosthesis and bowel-prosthesis anastomoses; 3) a transcutaneous abdominal wall prosthesis that bonds with skin, muscle, bladder, and peritoneum which resists external and intraluminal bacterial challenge; and 4) an air permeable, fluid impermeable filter which allows passive filling and gravity evacuation of urine. The principles involved have been successfully tested in rodents, rabbits, swine, and dogs. To date two total alloplastic prosthetic bladders fabricated from Biolor II and Proplast have been inserted in mini-swine for 4 weeks. PMID- 2252720 TI - Experimental studies of a hybrid artificial esophagus combined with autologous mucosal cells. AB - Preliminary results, obtained using an artificial esophagus combined with autologous mucosal cells in dogs, are reported. The authors' prosthesis is a silicone tube coated with freeze dried collagen sponge. Cells infiltrate this collagen layer and synthesize new tissue, which will become the neoesophagus. The silicone tube imparts rigidity to the prosthesis and prevents infection, leakage, and dislocation of the prosthesis at the anastomotic site. After formation of the epithelized neoesophageal lumen, the silicone tube drops into the stomach as the result of peristalsis in response to food. Eventually, no artificial prosthesis remains in place, and the defect is replaced by ingrowing tissue. This process was shortened by mucosal cell seeding. Before replacement, the authors harvested oral mucosal (OM) cells, cultured them for 10 days, and seeded them in the collagen layer of the prosthesis just after anastomosis. The neo-esophageal lumen was formed 1 week after the operation without any local complications, infection, leakage, or stenosis, and 2 weeks later the firm, epithelized neoesophagus was completed. OM cell seeding accelerated not only epithelization, but also regeneration of mesenchymal tissue. Parallel with this, transmission electron microscopy showed that most of the cells in the neoesophagus exhibited large nuclei and prominent rough endoplasmic reticulum, indicative of active collagen production. PMID- 2252721 TI - Prevention of infection in a porous tracheal prosthesis by omental wrapping. AB - The ideal tracheal prosthesis has to permit complete incorporation by epithelialization of the luminal surface. This is not possible with the currently available impermeable solid silicone tube. The authors developed a reinforced, porous polyurethane tubular prosthesis which has the potential for complete incorporation. However, because these prostheses are implanted in a contamined area such as the airway, they all become infected. In order to prevent infection, the authors evaluated the effect of omental wrapping in guinea pigs. The authors' tubular prosthesis was implanted subcutaneously in the abdominal area with the ends open to the air. Ten prostheses were wrapped with omentum and 10 prostheses were not. In 4 weeks, all control prostheses were infected and marsupialized. All the wrapped prostheses remained in place and were macroscopically not infected. Microscopically, all wrapped prostheses were well vascularized and were incorporated by granulation tissue, which did not occur in the prostheses of the control group. From these results the authors conclude that omental wrapping would be an effective way to prevent infection of porous tracheal prostheses in an open-to-the-air situation, and allow rapid tissue ingrowth and incorporation in the host. PMID- 2252722 TI - Measurement of back clearance. AB - With improvement in dialysis membranes, back filtration becomes the focus of study. Because new membranes that remove low molecular weight proteins, such as beta 2-microglobulin by diffusion are now available for clinical use, both back filtration and back diffusion become problems. This paper gives the mass transfer rate of solutes from the dialysate to blood compartment. As markers of toxic or antigenic substances, inulin (MW 5,200), lysozyme (MW 14,300), and alpha lactoalbumin (MW 14,400) were used. The dialyzers tested were the CLSU-12W, AM FP10, BK-1.0P, and FB-110U. The UFR controller set the flow rate on the blood side at 200, dialysate at 500, and ultrafiltration (QF) as 0 to 50 ml/min. Under these conditions, the inulin back clearance is 16 (CLSU) to 26 ml/min (FB), even if the QF is 50 ml/min, and is 10 to 34 ml/min for lysozyme at QF = 0 ml/min. Although a substantial amount of solute moves into the blood compartment, back clearance does not drastically decrease with increase in QF. To avoid contamination of the blood side, clean-up techniques for the dialysis line or online protein adsorber should be followed. PMID- 2252723 TI - Evaluation of plasma sodium concentration during hemodialysis by computerization of dialysate conductivity. AB - Kinetics modeling based on sodium mass balance and changes in conductivity at the dialysate outlet compared to that at the dialysate inlet, led to predicting the plasma water conductivity of the blood inlet. Conductivity transducers, with temperature compensation, located at the dialysate inlet and outlet ports of the dialyzer and connected to a conductimeter, were interfaced with a portable computer for data acquisition. In 38 dialysis sessions, a close relationship was found between estimated plasma water conductivity (CdBi) and measured plasma sodium concentration [Na]Bi, according to the formula: CdBi = 0.101[Na]Bi + 0.37 (n = 38; r = 0.922). The study shows that plasma sodium concentration at the dialyzer inlet could be evaluated, with a standard error of +/- 1.5 mEq/L, by continuous measurement of conductivity gradient between dialysate inlet and outlet. PMID- 2252724 TI - Effects of EPO therapy on backfiltration of dialysate in high flux dialysis. AB - The authors have developed a comprehensive mathematical model of the hemodialysis process to investigate the effect of r-HuEPO and the accompanying higher hematocrit on backfiltration in high flux dialysis. Model simulations indicate that under otherwise identical conditions typical of high flux dialysis, an increase in hematocrit from 20 to 33% will increase the amount of dialysate fluid entering the blood from 2.4 L to 3.8 L in a 4 hr treatment. We used the mathematical model to investigate the effect of the following variables on backfiltration: blood flow rate, ultrafiltration rate, inside fiber diameter, fiber length, and membrane permeability. While increasing the blood flow rate may enhance solute transport, it was found to increase backfiltration substantially through its effect on the axial pressure drop. This effect was most pronounced at the higher hematocrits due to the higher viscosity. It was found that increasing the fiber ID, decreasing the fiber length, and decreasing the permeability of the membrane (all at constant surface area) could be beneficial in reducing backfiltration. However, these results do not consider the potential negative impact of these changes on solute clearance. Finally, the mathematical model enhanced our understanding of the transport processes governing backfiltration. Due to protein concentration gradients in the lumen, protein osmotic pressures as high as 50-100 mmHg can be obtained in high-flux dialysis. As a result, providing an outlet hydrostatic blood pressure greater than the inlet hydrostatic dialysate pressure is not sufficient to guarantee the absence of backfiltration. PMID- 2252725 TI - Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy. AB - Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX. PMID- 2252726 TI - Pressure effects on roller pump blood flow during hemodialysis. AB - Accurate measurement of blood flow during hemodialysis is essential to avoid underdialysis. When blood roller pumps are pushed to the high-flow rates demanded by high performance dialyzers, flow may be overestimated. This study examined the effect of inflow (Pa) and outflow (Pv) pressures induced by hemodialysis roller pumps on flow in vitro and in vivo. Blood flow was measured volumetrically, and with an ultrasonic flow probe, whereas Pa was adjusted from -50 to -400 torr and Pv from 50 to 300 torr. Only Pa influenced flow. At -200 torr, true flow measured volumetrically averaged 8.5% +/- 1.3% less than the blood pump revolutions per minute (RPM) meter reading. At -400 torr, the difference was 33.0% +/- 1.9%. There was no visible indication that flow was reduced to less than pump meter readings. Pv, hematocrit, and the source of pump tubing had no significant effect. Flow measured with an ultrasonic transit-time probe during routine hemodialysis in 64 patients was 9.0% +/- 2.7% less than pump meter readings when Pa varied from -180 to -220 torr. Blood pump meter readings greater than 400 ml/min were usually inaccurate because of low Pa. Prepump monitoring of arterial inflow pressure can prevent hidden reductions in blood flow that decrease dialysis efficiency. PMID- 2252727 TI - Change in sympathetic activity before, during, and after dialysis-induced hypotension. AB - During the hemodialyses of eight patients with end-stage renal failure, who often had sudden-onset dialysis-induced hypotension, catecholamine (CA) levels were measured in the ultrafiltrate obtained by a mini-filter placed in series upstream of the dialyzer. The water evaporation rate from the skin (reflecting the perspiration rate) was also monitored. Results showed a temporary elevation in CA levels in the ultrafiltrate before hypotension occurred. This rise did not continue for long, returning to baseline when hypotension actually occurred. The temporary elevation may reflect transient compensation by the sympathetic nervous system for the decrease in vascular wall tension. It was also found that there was considerable water evaporation from the skin during hypotension. Because sweat gland activity is reflexively modulated by the baroreceptor, perspiration after a drop in blood pressure may reflect the normal diminiution in baroreceptor activity. PMID- 2252728 TI - Benefit of bicarbonate dialysis during CAVHD. AB - The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was examined during seven episodes of metabolic acidosis. When metabolic acidosis was not corrected with CAVHD, a sterile BD was substituted for either acetate- or lactate-based dialysate. Pre- and post-BD substitution levels of lactate, HCO3, PCO2, anion gap, and pH were recorded, as well as dose of intravenous (i.v.) bicarbonate. Improvements in pH and serum HCO3 were seen in all seven cases. Anion gap decreased in all but one of the patients who were switched from lactate to bicarbonate dialysate, with improvement most marked in those patients with marked elevation of the anion gap. No adverse effect on PCO2 was noted. Lactate dialysate may be less effective when serum lactate levels are high, and may contribute to further elevation of lactate levels and anion gap. These data suggest that bicarbonate dialysate may be preferable to lactate or acetate dialysate in CAVHD patients with persistent metabolic acidosis. PMID- 2252729 TI - Cardiopulmonary bypass with a surface-heparinized extracorporeal perfusion system. AB - To evaluate the effect of surface heparinization on platelet consumption during cardiopulmonary bypass (CPB) ten pigs were placed on CPB for 3 hours. All pigs were injected with autologous Indium-111 labeled platelets (300-420 uCi) 24 hours prior to CPB and were systemically heparinized prior to cannulation for CPB. CPB was established with a roller pump, a hollow fiber membrane oxygenator (HFMO, Bentley CM-50) and an arterial filter (AF, Bentley 1025). In six pigs the extracorporeal system was untreated whereas in four pigs it was surface heparinized with the Duraflo-II method. Cardiotomy suction was not used. Percent of injected radiation dose in HFMO and AF at 3 hours of CPB in the nontreated systems was 1.53 +/- 1.12 and 0.88 +/- 0.63%, whereas in the surface heparinized systems was 2.45 +/- 1.71 and 0.49 +/- 0.39% respectively (NS). (Values are mean +/- SD). Blood loss during (CPB) was 225 +/- 179 ml in the nontreated systems, and 263 +/- 103 ml in the surface heparinized systems (NS). Platelet counts were reduced by 12% or 21.8% at 3 hours of CPB in the two groups of pigs respectively (NS). No difference was observed in platelet consumption (in HFMO and in AF) or in platelet count reduction between the two groups of pigs. Surface heparinization did not improve platelet preservation in systemically heparinized pigs at 3 hours of CPB. PMID- 2252731 TI - Long-term experience with Swan Neck Missouri catheters. AB - The Swan Neck Missouri catheters are designed to reduce major complications including 1) exit/tunnel infections, by a downward directed exit hole; 2) pericatheter leaks, by placement of the deep cuff in the rectus muscle; 3) catheter tip migration, by caudal direction of the intraperitoneal segment; and 4) outer cuff extrusion, by a permanent bend between the 5 cm or 3 cm spaced cuffs in SN-M2 and SN-M3 catheters, respectively. Between April 1986 and April 1990, 103 swan neck catheters were implanted. Comparison of prospective data from 103 swan neck catheters and retrospective data from 148 standard (Tenckhoff and Toronto Western Hospital) catheters implanted between January 1982 and June 1985 showed reduced complication rates with swan neck catheters. An overall survival of 64% at 36 months for swan neck catheters is significantly better than that of 29% for standard catheters. PMID- 2252730 TI - ECMO assisted angioplasty for cardiomyopathy patients with unstable angina. AB - Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy. PMID- 2252732 TI - A prospective randomized evaluation of chronic peritoneal catheters. Insertion site and intraperitoneal segment. AB - The insertion site (midline or through the lateral rectus muscle) and type of chronic dialysis catheter (straight or spiral intraperitoneal segment) were evaluated in a prospective randomized trial. Dialysis catheter complications and catheter survival were the endpoints of evaluation. Eighty-five first catheters were evaluated. Neither race, gender, renal diagnosis, type of catheter, nor insertion site was a determinant of dialysis catheter survival. Overall median catheter survival was 308 days. There were 40 catheter complications (70%, n = 28) that occurred during the first 61 days following insertion. Median time to the first complication occurring within the first 61 days was 3 days. Late catheter removals were due to peritonitis episodes that failed to resolve. Complications are frequent with peritoneal dialysis catheters, and care of the peritoneal dialysis catheters requires constant vigilance. PMID- 2252733 TI - Complications of Tenckhoff catheters post removal. AB - Complications due to Tenckhoff catheters can occur at prolonged intervals after their removal. From January 1979 to October 1989, 431 patients at our center began continuous ambulatory peritoneal dialysis (CAPD), 278 of whom subsequently transferred to another form of renal replacement therapy. We identified 12 patients (4.3% or 12/278) with post removal catheter complications. There were 14 post removal complications, two each in two patients, and one in each of 12 others. The mean time to complication was 541 +/- 143 days (27-2,040). In 71% (10/14) of the complications, an abscess was found at the site of the previously removed Tenckhoff catheter. In 29% (4/14) of the complications, foreign body material consistent with a retained cuff was recovered. Documentation at the time of Tenckhoff catheter removal should include a statement regarding the presence of the Tenckhoff catheter cuffs, and patients with retained cuffs should be monitored closely for the development of abscesses or other complications. Immunocompromised patients are at high risk for these complications. PMID- 2252734 TI - Bioenergetic recovery processes of injured myocardium. AB - We employed cervically transplanted nonworking myocardium to simulate the condition of a heart supported by a ventricular assist device, and to investigate the bioenergetic recovery processes of injured myocardium with 31P nuclear magnetic resonance (NMR) techniques. A heterotopic graft was placed in the cervical portion of a recipient rat. One week later, a control 31P NMR spectrum was obtained from the graft. On the same day, the aorta of the graft was clamped for 30 minutes at room temperature. After this procedure, 31P NMR measurements of the graft were performed for 1 week. The phosphocreatine (PCr)/Inorganic phosphate (Pi) ratio, and beta-phosphate from adenosine triphosphate (beta ATP)/Pi ratio on the first and second day after injury were significantly lower than control (p less than 0.05). However, these ratios recovered to a significant extent on the third and fourth day. These results suggest that 3 or 4 days are required for bioenergetic recovery of reversibly injured myocardium, even under nonworking conditions. PMID- 2252735 TI - Additional salutary hemodynamic effects of the combined use of the paraaortic counterpulsation device and intraaortic balloon pump versus a paraaortic counterpulsation device alone. AB - The hemodynamic effects of the combined use of the paraaortic counterpulsation device (PACD) (stroke volume 65 ml) implanted on the ascending aorta, and a 20 ml intraaortic balloon pump (IABP) placed in the descending aorta, were compared with the PACD working alone in 12 dogs after the induction of heart failure. Heart failure was characterized by left ventricular end-diastolic pressure (LVEDP) greater than 18 mmHg and systolic aortic pressure (SAP) in stage A: 116 mmHg greater than or equal to SAP greater than 70 mmHg; in stage B: 70 mmHg greater than or equal to SAP greater than 30 mmHg; and in stage C: SAP less than or equal to 30 mmHg. Both modalities of mechanical assistance produced significant salutary hemodynamic effects in stages A and B. No difference was observed in stage C. In conclusion, the combined use of PACD and IABP is more effective than the use of either of these devices alone. This modality of mechanical assistance may easily be applied in patients that cannot be weaned from extracorporeal circulation, and in whom IABP was unsuccessfully applied. PMID- 2252737 TI - Hemodynamic effects of a new right ventricular assist device. AB - A right ventricular assist device (VAD) based on the principle of counterpulsation has been developed at our institution. The device is a valveless, pneumatically actuated, 40 cc, sac-type pump, with a single inlet outlet port. For right ventricular support, the "Uniport" pump is anastamosed end to-side to the pulmonary artery. In previous experimental trials, the device has been shown to impart minimal trauma to blood components. In this study, biventricular failure was induced in eight Holstein calves by normothermic ischemia during cardiopulmonary bypass. A Pierce-Donachy left VAD (LVAD) was used for left ventricular support following the ischemic insult. Hemodynamic measurements were obtained throughout the study, and each animal served as its own control. A significant increase in post injury cardiac output (33.5 +/- 11.4%) was obtained with use of the Uniport and LVAD, as compared to use of the LVAD alone (p less than or equal to 0.005). Other hemodynamic parameters of right heart failure, including right atrial pressure (RAP), pulmonary artery pressure (PAP), and left atrial pressure (LAP) were not significantly affected. These data suggest that the Uniport right ventricular assist device significantly improves cardiac output in this model of moderate right ventricular failure. Additional studies are required, however, to optimize pump stroke volume, and to further define the performance envelope of the device. PMID- 2252736 TI - A composite driving system for LVAS and IABP: practical and effective driving and weaning. AB - We have devised a new method, termed alternate synchronous driving (ASD), to wean patients from a left ventricular assist system (LVAS) to a pressure assist intraaortic balloon pump (IABP). We have built a new drive unit, VCT200, to apply ASD easily and automatically. After IABP insertion in the final weaning stage, this method drives the LVAS and IABP alternately, with electrocardiogram (ECG) synchronization. The pumping ratio of IABP increases while that of LVAS decreases according to recovery of natural heart function. In in vitro studies, ASD was effective when bypass flow (BF) was less than 50% of total flow (TF) (TF:BF + cardiac output [CO]), and its advantages increased under lower BF conditions. Mean aortic pressure (mAP) and CO increased 10 mmHg and 15%, respectively, with this method (IABP:LVAS = 1:1) when BF was 30% of TF. During in vivo studies, mAP increased 75.7 +/- 6.7 mmHg to 80.1 +/- 3.6 mmHg (p less than 0.001), and the CO increased from 3.1 +/- 0.5 L/min to 3.3 +/- 0.5 L/min (p less than 0.001), while the endocardial viability ratio (DPTI/TTI) increased 20-30%. This method was used in a 62-year-old man in which LVAS was applied after ventricular aneurysmectomy, BF was reduced from 2.2 L/min to 1.1 L/min by using ASD without any change in systemic perfusion. This reduction of BF could not be achieved with LVAS alone. From these data, this system could wean patients from LVAS and then switch to IABP smoothly, easily, and automatically, without hemodynamic instability. PMID- 2252738 TI - Left ventricular assist using a jet pump. AB - A simple, effective, cardiac assist device was developed using a jet pump, a device that performs pumping by energy transfer from a high speed jet to low speed surrounding fluids. This jet pump is inserted retrograde through the aorta and placed in the left ventricle transvalvularly. The jet of oxygenated venous blood entrains blood inside the left ventricle and pumps into the aorta through the aortic valve. Jet velocity is kept below the hemolytic threshold of 1000 cm/sec. The device was placed in a mock circulatory system that stimulates the left ventricle and vascular system by generating a pressure wave (120/75 mmHg) with a 4 L/min cardiac output (CO). A bypass loop (from the venous reservoir to aorta using a Biomedicus pump, Biomedicus Inc., Eden Prairie, MN) was set up, and the jet pump was installed. When the jet pump is turned on, bypass flow rate (BF) is 2.5 L/min, entrainment pumping 1.5 L/min, and peak ventricular pressure (VP) falls below aortic pressure (AP), while maintaining the mean AP. Time tension index (TTI) is decreased 31%. This result, when compared with simple bypass at differing BF, shows more than a 20% reduction in TTI. This simple jet pump provided significant unloading of the left ventricle and may be potentially useful as a left ventricular assist device. PMID- 2252739 TI - Light scattering detection of microemboli in an extracorporeal LVAD bovine model. AB - Thromboembolization studies were performed on two calves supported by extracorporeal left ventricular assist devices (LVAD) using a light scattering (He Ne Laser) microemboli detector (LSMD). The LSMD system was placed on the outflow cannula of the LVAD in the extracorporeal loop of each animal. The measurements included the size, number, and rate of production of circulating microemboli in the range 20 microns less than microemboli diameter less than 1,000 microns. These data were compared to independently and concurrently obtained measurements of emboli shear rate (CPF), platelet count, red blood count (RBC), leukocyte count (WBC), plasma free hemoglobin, factors XIII, X, and V, and sorbitol dehydrogenase. Embolic number and volume were seen to be most dynamic in the very early phases of acute thromboembolization (0-40 minutes) with a peak embolic response within the first 30 minutes. The dynamics of reduced emboli volume, rather than number, may be implicated in the later stages of the thromboembolic passivation of these ventricles. The LSMD results generally showed an inverse correlation of microemboli volume rate with CPF measurements for each ventricle. LSMD, CPF, and leukocyte and platelet counts, showed a direct correlation with reduced counts for each additional ventricle for both calves. Factor XII was seen to have a more direct correlation in time with LSMD measurements for each ventricle than other parameters under investigation. This study represents the first time laser scattering and filtration methods have been applied simultaneously with hematologic assays in order to study the dynamics of device associated thrombogenesis. PMID- 2252740 TI - Comparison of right ventricular and biventricular circulatory support in a porcine model of right heart failure. AB - The effects of right ventricular (RVAD) and biventricular assist devices (BVAD) in an acute porcine model of right heart ischemic failure produced by occluding the right coronary artery for 2 min (RCAO) were compared. Right and left ventricular pressures were measured with Millar transducers and respective septal to-free wall dimensions (RVSFWD, LVSFWD) with ultrasonic crystals. RCAO alone resulted in significant right heart failure, marked by a 36 +/- 5% reduction in cardiac output (pulmonary artery flow) and a 54 +/- 16% reduction in RV stroke work. Isolated RVAD significantly improved the hemodynamic conditions by restoring pulmonary blood flow and left heart filling to control levels. RVAD also resulted in reduced RVSFWD to control levels and increased LVSFWD via a rightward septal shift due to right heart unloading. Biventricular support resulted in the same hemodynamic improvement, but estimated LV peak systolic wall stress was reduced by 65 +/- 15% compared with control, due to concomitant LV unloading and reductions in LVSFWD. Therefore, either right or biventricular devices are effective in treating RV failure. The advantage of biventricular support is that the left ventricle is also unloaded, thus allowing improved circulatory support with minimal LV wall stress. PMID- 2252741 TI - Thromboembolytic complications during circulatory assistance with a centrifugal pump in patients with valvular prostheses. AB - This article describes two patients with artificial heart valves who suffered thromboembolytic complications during circulatory assistance using a Biomedicus centrifugal pump. The first case involved a 25-year-old man who presented acute blockage of a mechanical aortic valve. Emergency surgery was performed to replace this valve with a bioprosthesis. Postoperatively the patient developed severe left heart insufficiency and a Biomedicus centrifugal pump was placed between the left atrium and the ascending aorta. After 3 days of total left ventricular assistance, weaning was started and successfully completed with explanation on the 5th day. Two days later the patient died of multiple coronary embolism with thrombosis of the valve. The second case involved a 30-year-old man. Six months before, he underwent surgical procedure with placement of Bio-prosthesis for dissecting aortic aneurysm due to annuloectasia. Upon admission for terminal dilated myocardiopathy, the patient was in kidney failure almost requiring dialysis. Because of this patient's size (Marfan syndrome), no donor heart was immediately available and left circulatory assistance with a Biomedicus pump had to be initiated. The patient lived without mechanical ventilation, in good clinical condition until day 23 when he presented acute right heart failure due to extensive valvular and coronary thrombosis. From these two cases, several important comments can be made about anticoagulation therapy, partial unloading of left ventricle, or need for biventricular assistance, and efficiency of centrifugal devices in these clinical applications. PMID- 2252742 TI - The closing velocity of Baxter Duromedic heart valve prostheses. AB - The closing velocity of a mechanical heart valve (MHV) leaflet has been conventionally related to the valve sound, and possibly to recently observed MHV cavitation phenomenon. Presently, the MHV leaflet terminal closing velocity has been indirectly assessed either by listening to the valve sound and/or averaging over the closing period. Leaflet motion during the closing phase is not uniform. Using a laser sweeping technique developed in this laboratory, an experimental study was carried out to analyze the closing motion of Baxter Duromedic (DM) 29 mm mitral MHVs. The results were compared with that of a St. Jude Mechanical (SJ) 29 mm mitral MHV, using the same technique. The in vitro experiment was carried out by mounting the testing MHV at the mitral position of a mock circulatory testing facility, with heart rates ranging from 70-120 beats/min, ventricular pressure slopes (dp/dt) from 1800-5600 mmHg/sec, and cardiac outputs from 5.0-7.5 liters/min. This paper introduces the laser sweeping technique developed for precision monitoring of MHV leaflet motion, and presents the detailed leaflet motions within the last 3 degrees before final closure. The experimental results showed that the final closing velocity of DM, which is known to generate a louder valve sound and has a shorter closing period than that of SJ, actually has approximately the same closing velocity within the range of the experiment. Theoretical analysis further confirms that a short closing period may not lead to a higher leaflet final closing velocity. PMID- 2252743 TI - In vitro ultrasound characterization of a polyurethane trileaflet valve. AB - Polyurethane synthetic trileaflet valves were compared with commercial prostheses in vitro, in a pulse duplicator using ultrasound to characterize the flow velocities and patterns. Flow-pressure drop behavior was in the middle range of other prosthetic valves. Diastolic regurgitant jets were located by color Doppler ultrasound, and there appeared to be some leakage through the leaflet fold at the commissure. Nevertheless, the closing volumes and closed valve leakage volumes were, on average, lower than other prosthetic valves. Systolic 20 Hz spectral oscillations detected with pulsed Doppler and continuous wave Doppler were attributed to leaflet flutter in the open valve. PMID- 2252744 TI - Long-term echocardiographic follow-up of patients with a tricuspid bioprosthesis. AB - To clarify the long-term results of bioprosthetic valve function in the tricuspid position, 29 consecutive patients who underwent tricuspid valve replacement (TVR) were evaluated. There were 20 girls/women and 9 boys/men, with ages ranging from 6 to 61 years (mean 41.4 years). The bioprosthetic valves included Hancock in 2, and Carpentier-Edwards in 27. The follow-up period ranged from 32 to 145 months (mean 89 months). Regurgitant flow of the tricuspid bioprosthesis was studied by color Doppler echocardiography. Peak velocity (Vp) and pressure half time (PHT) were measured by continuous wave Doppler echocardiography. Operative mortality was 13.7% (4/29), with the actuarial survival rate, including operative deaths, 75% at 10 years. Valve thrombosis developed in one patient 4 years after TVR. Color Doppler showed regurgitation in 7 of the 20 patients who were completely followed up, but they were all asymptomatic and required no special intervention. Cusp tear or calcification requiring reoperation was not observed in this study, including 8 patients younger than 35 years of age. The Vp was significantly slower, and PHT was significantly prolonged, in the tricuspid rather than the mitral position. These data demonstrate that bioprosthetic valves in the tricuspid position can be used safely. Doppler examination should be performed taking these different flow dynamics into account. PMID- 2252745 TI - Hemodynamic influence of LVAD on right ventricular failure. AB - Left ventricular assist device (LVAD) pumping has hemodynamic and anatomic influences on right ventricular performance. A total artificial heart (TAH) model was employed to better understand the hemodynamic influence of an LVAD on the failing right ventricle. Biventricular failure was simulated by reducing both ventricular drive pressures of the TAH. After getting hemodynamic data, LVAD pumping in the case of right ventricular failure was simulated by increasing just the left ventricular drive pressure. In the LVAD-simulating condition, cardiac output increased and right atrial pressure decreased significantly (p less than 0.05) compared with the biventricular failure condition, whereas right ventricular function and minute work were the same in these two conditions. Even though changes were accompanied by adaptive increases in pulmonary resistance, substantially lower pulmonary artery and left atrial pressures resulted in the LVAD-simulating condition. From a hemodynamic perspective, these results indicate that an LVAD can increase right ventricular volume work by decreasing right ventricular pressure work, whereas right ventricular net pressure-volume work is unchanged and right ventricular failure is not worsened. PMID- 2252747 TI - Left ventricular versus left atrial cannulation for the Thoratec ventricular assist device. AB - In a retrospective study of 28 patients (23 men, 5 women) supported with ventricular assist devices greater than 3 days, the effect of LV cannulation versus LA cannulation on device performance was compared. Patients ranged in age from 12 to 67 years (mean 46 years) and were supported for 3-81 days (mean 15 years). Fifteen patients were supported with left VADs (6 LV and 9 LA), and 13 patients were supported with BVADs (5 LV and 8 LA). The mode of operation 91% of the time was the fill-to-empty mode. Ten data points were taken for each patient. LV cannulation results in higher VAD flow index at decreased preload, lower VAD systolic and vacuum pressures, and shorter diastolic durations. Eleven of the 28 patients survived. Although survival was greater in patients with LV cannulation, survival was more dependent upon reversibility of myocardial damage, eligibility for transplantation, or the development of complications. These data indicate that LV cannulation provides better VAD performance than LA cannulation in the fill-to-empty mode. PMID- 2252746 TI - Physiologic reactions of awake animals to an immediate switch from a pulsatile to nonpulsatile systemic circulation. AB - The purpose of this study is to clarify physiologic reactions to an immediate switch of flow pattern from pulsatile to nonpulsatile. A pulsatile ventricular assist device (VAD) was implanted in four 40-64 kg goats. Blood was drawn from the left atrium and ventricle and expelled into the aorta. After 2 weeks the VAD was quickly replaced by a centrifugal pump, MD-10 (Iwaki Pump, Tokyo, Japan), 760 g in weight and phi 70 mm x 84 mm in size, set on the back, without anesthesia. A 100% nonpulsatile bypass flow was immediately obtained, and the pump was set to maintain the same mean aortic pressure as before the switch; central venous pressure, cardiac output, systemic vascular resistance, oxygen consumption, blood lactate, plasma adrenalin, noradrenalin, renin activity, angiotensin II, and aldosterone were measured. Behavior of the goats did not change, and fluid infusion and higher cardiac outputs were not required. Most of the parameters did not deviate from control levels after the switch. In conclusion, a mammal immediately accommodates well to nonpulsatile flow. PMID- 2252748 TI - Early and late tamponade with the Novacor left ventricular assist system. AB - Cardiac tamponade can be a major complication after implantation of the Novacor left ventricular assist system (LVAS). Between 1987 and 1989, 14 patients received an LVAS as a bridge to cardiac transplantation: 3 developed early tamponade (33 +/- 12 hr postoperatively) and 5 were diagnosed with a late tamponade (9.4 +/- 3.2 days postoperatively). One patient had both early and late tamponade. Early tamponade was more common in those with increased perioperative blood loss (5,270 +/- 1,942 ml vs. 1,420 +/- 1,160 ml in other patients, p less than 0.05). Early tamponade was suggested by reduction in mean arterial pressure (74 +/- 1 to 64 +/- 3 mmHg), LVAS output (5 +/- 0.5 to 2.7 +/- 0.7 L/min), LVAS stroke volume (55 +/- 4 to 23 +/- 5 ml), and an increase in central venous pressure (13 +/- 1 to 21 +/- 1 mmHg, p less than 0.05 for all values). Late tamponade was associated with a marked rise in central venous pressure (14 +/- 1 to 22 +/- 2 mmHg, p less than 0.05), with only a mild decrease in LVAS output (4.9 +/- 1 to 3.8 +/- 0.9 L/min) and stroke volume (49 +/- 8 to 36 +/- 3 ml), without a significant change in mean arterial pressure. Two of these five late episodes occurred in patients who were anticoagulated with heparin (PTT 52 and 100 sec), and in one other with warfarin (PT 27 sec, PTT 55 sec); two patients were not on any anticoagulants. Surgical drainage of pericardial effusions, and especially of clotted blood found frequently posterior to the left ventricle in the space created by the LVAS decompressed left ventricle, resulted in an immediate return of all hemodynamic measurements to normal in both early and late tamponade. PMID- 2252749 TI - Prognosis of hospital survivors after salvage from cardiopulmonary bypass with centrifugal cardiac assist. AB - Since October 1986, 6 hospital survivors who were salvaged from cardiopulmonary bypass (CPB) with the Sarns centrifugal pump were observed. Centrifugal assist was employed only after failure to wean with usual resuscitative measures, including multiple high dose inotropes and intraaortic balloon pumping. There were five men and one woman, 46-59 years of age (mean 61 years). All patients had undergone coronary artery bypass grafting, with two patients having had concomitant left ventricular aneurysmectomy and two aortic valve replacement. Five patients had left ventricular assist only and one had biventricular assist. Duration of assist ranged from 26 to 72 hr (mean 48 hr). Complications were ubiquitous, and the resultant prolonged hospitalization was resource intensive. All hospital survivors remain alive and are in New York Heart Association functional Class II, with an average follow-up of 24 months, (6-41 months). Compared with preoperative values, current left ventricular function is improved in 2 patients, has deteriorated in 3, and is unchanged in 1. Thus, the Sarns centrifugal pump will allow salvage of some patients who otherwise are not weanable from CPB. Survivors can expect a reasonable functional capacity as reflected by this experience. PMID- 2252750 TI - Development of micropatterning technology for cultured cells. AB - The manipulation of regional cell adhesiveness by surface design could provide micropatterned cell culturing. Based on the photoreactive chemistry of a phenylazide group, a novel surface micropatterning technology for cultured cells was successfully developed. The principle is as follows: 1) a photoreactive hydrophilic co-polymer with phenylazide was cast on a hydrophobic matrix surface, 2) a photoreactive hydrophobic co-polymer was cast on a hydrophilic matrix; 3) a photomask with a given pattern was tightly placed on the cast film; and 4) after UV irradiation and subsequent washing, bovine endothelial cells (ECs) were seeded and cultured. ECs adhered and grew only on nonhydrophilic regions, eventually resulting in micropatterning of ECs. The micropatterns of cultured ECs prepared by 1) and 2) were negative- and positive-type patterns to that of the photomask used, respectively. PMID- 2252751 TI - Development of a novel potent peptidyl platelet preserving agent: molecular design and biologic activity. AB - This paper reports the molecular design of potent peptidyl platelet preserving agents. The principal structural feature of the designed agents has an RGD(Arg Gly-Asp) sequence in a molecule, which is the adhesive site of adhesive proteins, such as fibrinogen. From conformational analyses and inhibitory effects on adhesion and aggregation of platelets, the logical design criteria aimed at enhanced antiplatelet activities depended upon enforcement of beta-turn structure or spacial rigidity of RGD sequences. The dose-dependent inhibitory effect on platelet aggregation induced by collagen showed that a ten-fold higher activity was found for a linear decapeptide, VVVRGDSVVV (V = Val), and a 100-fold increase for cyclic tetrapeptide, cyclo(RGDG), as compared with RGDS (half inhibition concentration, 0.1 mmol/L). Very potent antiplatelet agents, specially designed for the cardiopulmonary circulation, were successfully developed. PMID- 2252752 TI - The force of detachment of endothelial cells from different solid surfaces. AB - With the use of a technique based on the detachment of single cells by suctioning of the cells with a glass micropipette, the authors studied human endothelial cell adhesion on 4 different surfaces (Fluorocarbon FC 721, polyester, nylon, glass) versus time of contact in phosphate buffered solution and a complete culture medium. It was observed that the force of detachment from solid surfaces of endothelial cells increases significantly with time and with increasing substrate surface tension in PBS and decreasing substrate surface tension in complete culture medium. This dependence of cell-fiber interactions with surface tension of the fibers demonstrates that cell adhesion in the authors' experimental conditions in primarily controlled by surface tension. PMID- 2252753 TI - A hydrogel pericardial patch. AB - Patients undergoing repeat cardiac operations are higher operative risks than those undergoing an initial cardiac procedure because adhesion formation can occur if the native pericardium is not closed. A unique composite patch that may be used to augment the pericardial tissue when primary closure is not possible has been developed. The patch is made of a hydrogel, poly (2-hydroxyethyl methacrylate), reinforced with an ethylene tetrafluoroethylene (ETFE) mesh. The mesh provides the needed mechanical properties, whereas the patch's surface properties are comparable to the hydrogel. Two types of patches were fabricated: one with the mesh weave at a perpendicular orientation and one at 45 degrees to the principle loading direction. The patches were mechanically tested and compared with canine pericardium. Ultimate tensile strength of the patches is not significantly different from canine pericardium (p less than 0.05), are the patch suture strength is nearly twice that of canine pericardium. The perpendicular patch is stiffer than canine pericardium, whereas the 45 degree patch is not (p less than 0.05). The 45 degree patch shows considerable promise as a pericardial substitute because it closely matches the properties native canine pericardium. PMID- 2252754 TI - Phenotypic characterization of monocytes and macrophages from CAPD patients. AB - The purpose of this study was to phenotypically characterize and compare peripheral blood monocytes from CAPD patients with peritoneal macrophages isolated from their peritoneal dialysis effluents. Monocytes/macrophages were labeled with fluorescent ligands or monoclonal antibodies specific for 1) receptors for C5a, formyl-met-leu-phe (fMLP); Fc region of IgG; C3b (CR1); and C3bi (CR3), 2) Class II histocompatibility antigens HLA-DR and HLA-DQ; and 3) monocyte/macrophage surface antigen CD14. The cells were analyzed using flow cytometry. Results indicated that there were no differences between monocytes and peritoneal macrophages in their receptor expression for fMLP, CR1, or CR3. However, paired t-testing indicated that peritoneal macrophages had significantly increased expression of Fc and C5a receptors, as well as enhanced antigen expression of HLA-DR, HLA-DQ, and CD14. These results suggest that peritoneal macrophages from CAPD patients are activated with increased expression of receptors and antigens important in host defense. PMID- 2252755 TI - Therapeutic effects of simvastatin on hyperlipidemia in CAPD patients. AB - A causal link between hypercholesterolemia due to elevated plasma concentrations of LDL and VLDL remnants of CAPD patients has been established. The effects of 24 weeks of treatment with Simvastatin, a new HMG coenzyme A-reductase inhibitor (at 20 and 40 mg/day) on serum lipid, lipoprotein, and apolipoprotein A-I and B concentrations, as well as safety parameters and subjective side effects, were evaluated in eight patients (mean duration CAPD 24.80 +/- 7.50 months, age 54.50 +/- 13.70 years). Maximal effects on plasma lipoprotein and apolipoprotein concentrations were achieved after 4 weeks, and remained stable thereafter during the study. Mean fasting plasma cholesterol concentrations decreased from 280.5 +/ 60.2 mg% to 190.2 +/- 40.4 mg/dl (p less than 0.005) (-47%); mean plasma LDL cholesterol concentrations also decreased from 257.6 +/- 13.4 mg% to 190.5 +/- 15.4 mg/dl (p less than 0.001) (-35%). Apolipoprotein A and B concentrations decreased significantly from 1.78 +/- 0.19 to 1.40 +/- 0.22 g/L (p less than .005) and 1.81 +/- 0.26 to 1.38 +/- 0.20 g/L (p less than .005). These data substantiate the view that Simvastatin is well tolerated and that no serious clinical or adverse laboratory effects have been observed. It appears to be a promising drug for the effective control of hyperlipemia in a large proportion of hypercholesterolemic patients, reducing their cardiovascular morbidity while on CAPD. PMID- 2252756 TI - Influence of phosphatidylcholine on ultrafiltration and solute transfer in CAPD patients. AB - Fifteen patients (mean age 59.9 +/- 16.1 years) treated by CAPD for a mean of 21.6 +/- 14 months, underwent peritoneal clearances before and after 15 days of intraperitoneal phosphatidylcholine (PC) treatment (50 mg/L). No difference was observed in urea, creatinine, uric acid, and reverse dextrose clearances. A statistically significant increase in phosphate clearances (4 and 6 hr dwell times) (1.36%) and a reduction in drainage volume (2 hr dwell time) (1.36%) were observed after treatment. Urine output and percent dextrose reabsorption were unchanged. The ultrafiltration (UF) showed a tendency to increase, which lasted for 15 days after discontinuation of treatment. This tendency allowed the patients to reduce, during the same period, the amount of hypertonic solution (23.8 L vs. 21.3 L) required. The tendency to increase UF over time deserves further study. PMID- 2252757 TI - Chronic nightly tidal peritoneal dialysis. AB - Nightly tidal peritoneal dialysis (NTPD) is a technique in which, after an initial fill of the peritoneal cavity, only a portion of dialysate is rapidly cycled. Five anuric, stable, PD patients entered a 4 month study to determine the NTPD session length necessary for clinically adequate dialysis and creatinine clearance similar to those on four daily 2 L CAPD exchanges. NTPD was performed using a modified PAC-X-2 cycler, with the drain phase regulated by a target volume. One patient completed 3.5 months of study, one 4 months, three 6 months, and one patient each continued on NTPD for 13, 14, and 32 months. The mean NTPD session time was 9 hr 24 min (range 8 hr 35 min to 9 hr 55 min) at the end of 4 months. All patients had clinically adequate dialysis. Three patients preferred NTPD over CAPD, particularly because of an empty abdomen during the daytime. One patient required an increase in NTPD time, and an addition of one daytime exchange, because of low creatinine clearance. In conclusion, NTPD provides weekly creatinine clearances comparable to CAPD, with an acceptable duration of nightly dialysis sessions in most anuric patients. A new PD machine providing inexpensive dialysis solution in large quantities, as well as safe and false alarm free dialysis sessions, is needed for practical NTPD implementation. PMID- 2252758 TI - Development and evaluation of a wearable blood glucose monitor. AB - Complex operation, prolonged set-up time, reliability problems, high cost, and excessive size limits the use of currently available extracorporeal continuous blood glucose analyzers. A self-calibrating, wearable blood glucose monitor has been developed to overcome these impediments. The wearable blood glucose monitor is a 410 g forearm-mounted instrument with three miniature pumps for blood sampling, calibration, and insulin infusion, and a flow cell containing an enzyme electrode sensor capable of determining plasma glucose levels accurately and precisely in undiluted whole blood. The unit is connected to a computer controller with graphics display. Venous blood is drawn from a 21 gauge single lumen cannula through the sensor flow cell. A rate determination of glucose is completed in 20 sec and the blood is returned to the arm vein. Heparinized saline wash solution follows. No blood loss or significant systemic heparinization occurs. Cycle time is set from 2 to 5 min. The method is linear to at least 300 mg/dl glucose, independent of hematocrit, and free of interferences from blood constituents at normal venous pO2 with a coefficient of variation of 1-3% between calibrations. The sensor has a service life of at least 3 weeks. This wearable blood glucose monitor, with its high performance sensor, reduced size, and ease of operation, shows promise for evaluating and treating diabetes. PMID- 2252759 TI - In vitro and in vivo testing of an electrocatalytic glucose sensor. AB - A prerequisite for the development of an implantable artificial pancreas is the availability of a stable, long-life glucose sensor. Platinum (Pt) catalyzed electrodes have been demonstrated in vitro to show high sensitivity to glucose and long cycle life but are more sensitive to co-reactants compared with enzymatic methods. The authors developed a special data processing method (compensated net charge ratio, or CNCR) in which the measured electrode response is very sensitive to glucose, completely insensitive to urea, and only moderately sensitive to amino acids. Other endogenous and exogenous co-reactants show only minor interferences. The CNCR method involves the determination of the ratio of net oxidation charge to total charge during one complete cycle of a cyclic voltammogram. Prototype electrodes tested in vitro in spiked plasma have shown typical sensitivities of greater than 2 x 10(-4) CNCR units per 1 mg/dl change in glucose concentration, with linear response up to 400 mg/dl. For in vivo testing, a modified 5 F vascular catheter with membrane covered surface mounted electrodes was used at a vena cava site in swine. Several sensor designs were tested in vivo, with sensitivities of 1-5 x 10(-4) CNCR units (mg/dl). PMID- 2252760 TI - Time and pressure dependence of sieving coefficients during membrane plasma fractionation. AB - The apparent sieving coefficient (S') of a membrane, defined as the ratio of permeate to feed concentration, is not an intrinsic property of the membrane, but depends upon operating conditions. The variation of albumin, IgG, and IgM sieving coefficients with time during dead-end filtration was investigated using human pooled plasma and two types of hollow fiber filters (cellulose acetate PF 100 and ethylene vinyl alcohol Eval 2A). For the same filtrate flux (3.6 10(-3) cm/min) the transmembrane pressure (TMP) rises faster with time for the Eval filter because of its smaller hydraulic permeability (0.26 10(-4) cm/min mmHg vs. 7.3 10(-4). The albumin S' of the PF 100 reaches 0.95 after 20 min of filtration but drops to 0.4 after 50 min, whereas the S' of the Eval filter, which never exceeds 0.6, remains at this level for at least 50 min. By varying the inlet flow rate the authors show that for a given membrane, the critical parameter that governs the S' is the TMP. These data suggest that it is essential to specify the TMP when quoting a value of S', and the most permeable membrane, with the highest maximum S', is not necessarily the one that maximizes the overall recovery over a long period. PMID- 2252761 TI - A simple and accurate method for prescribing plasma exchange. AB - During plasma exchange, prediction of treatment results requires an estimate of plasma volume (EPV). Using a simplified formula for EPV, EPV = [0.065 X wt(kg)] X [1-Hct], the predicted and actual decline in serum levels of several large molecular weight substances was evaluated during 102 treatments in 18 patients. Predicted as opposed to actual percent of decline in serum levels for IgG was 67 +/- 7% vs. 64 +/- 10% (+/- SD, R = 0.66, n = 40, p = 0.0001); for IgA was 66 +/- 8% vs. 66 +/- 9% (R = 0.59, n = 36, p = 0.0001); and for IgM was 66 +/- 7% vs. 69 +/- 8% (R = 0.63, n = 39, p = 0.0001). For the third component of complement the values were 58 +/- 7% vs. 61 +/- 5% (R = 0.73, n = 17, p = 0.009), and for total cholesterol 66 +/- 3% vs. 70 +/- 4% (R = 0.62, n = 28, p = 0.005). It can be concluded that a simplified method for estimating plasma exchange allows for a reasonably reliable prediction of treatment results. PMID- 2252762 TI - Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia reperfusion injury in liver transplantation. AB - This study evaluated the effects of a prostaglandin I2 analogue (aPGI2), superoxide dismutase (SOD), and catalase (CAT) on hepatic injury after warm ischemia and reperfusion in terms of survival, mitochondrial function, serum enzymes, and histology. Hepatic ischemia was created in rats by clamping the hepatoduodenal ligament for 90 min with splenofemoral bypass. Reperfusion was induced by unclamping the vessels and disconnecting the splenofemoral bypass. Then aPGI2 (350 ng/kg/min) was infused for 60 min just before hepatic ischemia, and SOD and CAT (5,000 units/kg each) were administered immediately before the start of reperfusion. Serum enzyme and mitochondrial function assessments of livers were made just after ischemia, and after 2 hr of reperfusion. Survival rate was also assessed in a separate group of rats. Liver enzymes such as SGOT, SGPT, and LDH showed no correlation to liver viability. The administration of aPGI2 alone showed no effect on ischemically injured mitochondria; however, the free radical scavengers (SOD, CAT), in combination with aPGI2, showed significant improvement of mitochondrial function together with extension of survival. The ultrastructure of hepatocytes was better preserved in the treated groups. These agents improved the viability of ischemic-reperfused injured livers. PMID- 2252763 TI - An extracorporeal perfusion system to bridge pediatric liver transplant candidates. AB - An extracorporeal liver perfusion system was designed to maintain cadaver livers in an oxygenated, normothermic state for bridging procedures for hepatic transplantation. Nonpulsatile high flow and pulsatile low flow blood are supplied to the portal venous (PV) and hepatic arterial (HA) circulations. Controlled low blood flow (5-10 cc/kg [patient]/min) is exchanged between the high flow extracorporeal perfusion circuit (1 cc/g [liver]/min) and the patient. The system was evaluated in perfusions of fresh, excised pig livers (n = 5). The average oxygen consumption was 9 +/- 3 microliters/g/min, and bile production averaged 4.7 microliters/g/hr. Perfusion pressures and flows were normal in both the HA and PV circulations for about 4 hr. Pressures then gradually rose, especially in the HA circulation, causing flow to decrease, with subsequent mottling and discoloration of the liver. Red blood cell, platelet, and white blood cell counts fell continuously. Maintenance of liver function was assessed by clearance of an 80 mg taurocholic acid challenge. An average of 56% of injected acid was cleared from the perfused livers (n = 5) in the first half hour, compared with 90% and 25% for the in situ (n = 3) and unperfused (n = 3) control livers, respectively. The system consistently maintained livers in a moderately well functioning state through the first 4 hr of perfusion. Adequate support of animals with induced hepatic failure must now be demonstrated. PMID- 2252764 TI - Sulfation and glucuronidation of acetaminophen by cultured hepatocytes replicating in vivo metabolism. AB - A requirement of hepatocytes incorporated into an artificial liver support system will be preservation of in vivo metabolism of the cultured hepatocytes. The metabolic fate of a low (15 mg/kg), medium (125 mg/kg), and high (300 mg/kg) dose of acetaminophen (APAP) was determined in male and female rats. Male rats excreted more APAP as the sulfate conjugate than female rats, which correlated with the twofold greater APAP sulfotransferase activity in the male versus female rats (301 +/- 24 vs. 156 +/- 18 pmol/mg protein/min). Also, as sulfate conjugation became saturated, there was a dose-related shift in APAP metabolism to glucuronide conjugation in both genders. After sacrifice, hepatocytes were cultured with APAP (0, 150, 250, 500, and 1,000 microM). Gender differences in APAP sulfation and glucuronidation persisted in culture for up to 4 days, with sulfation predominating in the male rats, similar to that seen in vivo. With increasing APAP dose, there was a saturation of sulfate conjugation and a shift to glucuronidation as observed in vivo. APAP sulfation and glucuronidation by freshly isolated cultured hepatocytes in vitro can replicate in vivo metabolism. PMID- 2252765 TI - An efficient method for removing bilirubin. AB - Bilirubin is tightly bound to albumin, making hemoperfusion an ineffective treatment for hyperbilirubinemia. By adding a safe unbinding agent to the blood (solutizer), which itself is adsorbed, hemoperfusion can become efficient and practical. Canines were made hyperbilirubinemic with an intravenous infusion of a 5 mg/ml solution (with Na2CO3) for 1 hour. Peak concentrations of 14-22 mg/dl were reached in adult dogs (25-35 kg). Hemoperfusion was then initiated with or without (control) the solutizer (sodium benzoate). The bilirubin unbinding effect of sodium benzoate was rapid and effective. Because of the simultaneous adsorption of sodium benzoate, a small activated carbon section that was presaturated with the solutizer was located proximal to the main hemoperfusion column, in addition to continuous infusion to reach 20 mM in the blood. Comparison of the normalized bilirubin concentration for benzoate augmented hemoperfusion with the average for control dogs, shows that benzoate results in a threefold decrease in the normalized bilirubin concentration after 1.5 hr of hemoperfusion. Sodium benzoate may also have the advantage of protecting platelets during hemoperfusion. PMID- 2252766 TI - Experience with the Sarns centrifugal pump as a ventricular assist device. AB - The authors used the Sarns centrifugal pump (Sarns 3M, Ann Arbor, MI) as a ventricular assist device (VAD) in 30 patients between May 1985 and February 1990. Sixteen patients were unweanable from cardiopulmonary bypass at the time of surgery; nine were patients who developed cardiogenic shock postoperatively in the intensive care unit. One was a donor organ failure; one had a failed PTCA; and one an acute myocardial infarction with cardiogenic shock preoperatively. Two patients were bridged to cardiac transplantation. Of the 28 nontransplant candidates, 20 (71.4%) were weaned successfully, 14 (50%) were discharged from the hospital, and 13 (46%) are alive from 1 to 46 months postoperatively (mean, 21.1 months). Three patients received right ventricular support alone; all three were weaned, and two (66.7%) were discharged. Ten patients received left ventricular assistance alone. Six (60%) were weaned, and four (40%) were discharged. Two patients received left ventricular support initially but were taken back for right VAD insertion because of right-sided heart failure; one (50%) is alive. Fifteen patients received biventricular support. Eleven (77.3%) were weaned, and eight (53.3%) were discharged. Patient ages ranged from 19 to 73 years, with a mean age for men of 59 years and 50.5 years for women. There were no thromboembolic events. Various clinical parameters were evaluated to determine effect on weanability and survival. These results show survival equivalent to any other VAD at this time. The centrifugal pump is a convenient and effective means of maintaining ventricular support in individuals who are believed to have salvageable myocardium. PMID- 2252767 TI - Hemopump ventricular support for patients undergoing high risk coronary angioplasty. AB - Prophylactic implantation of a Hemopump (Johnson and Johnson, Skillman, NJ) has been evaluated in nine patients selected for high risk coronary angioplasty. They were unstable patients, refractory to maximal pharmacology, with indications for revascularization, but contraindications for surgery such as low ejection fraction and lack of material for bypass. In all, the target lesion was located on the last patent vessel. The pump was inserted under local anesthesia, without any graft. A specially designed occluder permitted avoidance of retrograde bleeding during implantation. The bypass flow ranged from 2.5 to 3.2 L/min, and permitted a rise in cardiac index from 2.05 to 2.55 L/min/m2, with a drop in capillary wedge pressure from 13 (7-18) to 10 (7-13) mmHg. During balloon inflation, no electrocardiographic changes were observed, because only minor ventricular arrhythmias occurred. No significant hemolysis was seen (plasma free hemoglobin less than 10 mg/dl in all) after 2 hr of pumping. The only limitation of the technique appears to be difficulty at the time of implantation from narrow, stenosed, or tortuous iliofemoral arteries (3 patients). This experience strongly supports the benefit of temporary left ventricular Hemopump support in high-risk situations and clearly shows the need for a smaller pump. PMID- 2252768 TI - Improved survival after Hemopump insertion in patients experiencing postcardiotomy cardiogenic shock during cardiopulmonary bypass. AB - Immediate placement of a Hemopump (HP) ventricular assist device was undertaken in nine patients (seven men, two women) after other attempts at weaning from cardiopulmonary bypass (CPB) after coronary bypass surgery had failed. All nine patients (100%) were successfully weaned from CPB, and six (63.3%) gradually improved enough to permit removal of HP support. Five (83.3%) of the six who were weaned from CPB survived beyond hospital discharge. HP support was evaluated in terms of vital organ function, incidence of complications, and clinical outcome. In both survivors (S) and nonsurvivors (NS), serial hemodynamic measurements were taken. Although there were few differences in hemodynamic parameters between groups at 4 hr, by 24 hr the S group had markedly improved cardiac index, Glasgow Coma Scale, urinary output, and pulse pressure and required far less inotropic support than did the NS group. All four patients who required high dose inotropic agents to maintain acceptable end-organ perfusion on HP support died; three were unable to tolerate weaning from the HP, and all died within 72 hr of surgery because of ineffective myocardial recovery. None of the survivors required additional early inotropic augmentation. Renal perfusion appeared to be well maintained, even with mean arterial pressures below 60 mmHg during HP support. There were no episodes of hemolysis, infection, or limb ischemia in either group. Thus, the Hemopump provided excellent circulatory support for those patients who could not be weaned from CPB by traditional methods. PMID- 2252770 TI - Clinical experience with the Nimbus pump. AB - The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy. PMID- 2252769 TI - Hemopump support for the failing heart. AB - Under fluoroscopy, the hemopump is passed through the aortic valve into the left ventricle through a Gortex (WF Gore, Denver, CO) chimney sewn to a surgically exposed femoral artery. The system aspirates the left ventricular blood and actively pumps it into the aorta. Five patients (four men, one woman), aged 47-71 years (mean, 62 years), were candidates for hemopump support because of refractory cardiogenic shock. Three were recovering from repeated coronary artery bypass graft (CABG) surgery, and two required postoperative emergency CABG for failed percutaneous transluminal coronary angioplasty (PTCA). One patient died during insertion, and four had the hemo-pump successfully placed. All patients had low cardiac out-put and had intraaortic balloons in place. Average insertion time took 20 min, with maintenance on the hemopump for an average of 13 hr. One patient was maintained on the hemopump for 12 hr, but because of continued deterioration, was placed on a total artificial heart (Harvik 7-70). Patients 3 (hemopump inserted transthoracically) and 4 had the hemopump discontinued because of brain death, and the fifth survived. This patient is alive and working 1 yr later. The hemopump is an effective left ventricular support system that is less invasive than conventional transthoracic systems. PMID- 2252771 TI - Biocompatibility of dialysis membranes is of no importance for objective or subjective symptoms during or after hemodialysis. AB - The clinical importance of biocompatibility of hemodialysis membranes is a matter of controversy. The authors studied the relationship between biocompatibility and acute symptoms during hemodialysis (HD). Twenty-three patients underwent 12 different bicarbonate HD using Cuprophan, Hemophan, or Polyamide membranes for short (2 hr) and long (4 hr) treatments, with small or large membrane areas. Subjective and objective symptoms were registered during HD and 12 and 36 hours thereafter. Type of membrane, membrane area, or Kt/V were of no importance for the occurrence of subjective or objective symptoms. The patients registered fewer symptoms during 2 hr HD with high blood flow than during 4 hr HD with slow blood flow (p = 0.04). Headache was particularly more frequent during the 4 hr HD. Blood pressure, and to some extent subjective symptoms, were influenced by ultrafiltration volume but not by type of membrane. Biocompatibility is not a determinant of acute side effects of hemodialysis. PMID- 2252772 TI - Clinical effects of a polyethylene glycol grafted cellulose membrane on thrombogenicity and biocompatibility during hemodialysis. AB - The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD. PMID- 2252773 TI - Difference in beta 2-microglobulin removal between cellulosic and synthetic polymer membrane dialyzers. AB - Several kinds of dialyzers, with highly permeable membranes (HPM), have been designed to specifically remove beta 2-microglobulin (BMG). To clarify their solute transport characteristics, nine types of HPM dialyzers were evaluated during in vivo and in vitro studies using human plasma and aqueous solutions. No BMG membrane adsorption and/or plugging was seen with cellulosic membrane dialyzers during in vitro experiments using human plasma. On the other hand, all synthetic polymer membrane dialyzers had adsorptive properties, and in a dialyzer with a polymethylmethacrylate membrane, a large amount of BMG was removed by adsorption alone. Dialyzers with cellulose triacetate and polyacrylonitril membranes showed higher values of BMG diffusive dialysance (greater than 20 ml/min) and sieving coefficient (greater than 0.9). From in vitro experiments using an aqueous solution containing several solutes with relatively small or middle molecular weights, all HPM dialyzers had a higher overall mass transfer coefficient than any conventional membrane dialyzer. PMID- 2252774 TI - Endothelial injury during extracorporeal circulation. Role of the complement system. AB - This study attempted to elucidate in vitro, endothelial cell (EC) injury induced by complement activation in extracorporeal devices. The in vitro injury model using cultured bovine ECs showed the following: 1) a dose-dependent transmembrane injury, determined by monitoring intracellular calcium mobilization, occurred spontaneously upon addition of complement-activated serum. 2) The respiratory rate of adherent ECs, monitored by an oxygen electrode, was reduced with increases in activated complement serum levels, and increased further with time. 3) Whole cell activity, measured by the rate of cellular proliferation, was reduced with an increase in activated serum complement levels. 4) These cellular responses were almost completely absent in the presence of C3 antiserum, strongly indicating that activated C3 fragments are responsible for EC injury. Thus, complement activation during extracorporeal circulation may injure endothelium at the transmembranous, mitochondrial, and/or proliferative levels, depending upon contact time and concentration of activated complement. PMID- 2252775 TI - Evaluation of Duraflo II heparin immobilized cardiopulmonary bypass circuits. AB - Cardiopulmonary bypass (CPB) involves extensive contact between blood and synthetic surfaces and may result in blood cell activation and plasma protein alterations. This study determines the effect of Duraflo II heparin treated CPB circuits (Bentley Laboratories, Irvine, CA) on calves under simulated clinical conditions. Calves were placed on CPB for 4 hr, and activated clotting times were maintained above 480 sec with systemic heparin. Better preserved platelet number and function, lower fibrinopeptide A levels, and lack of thrombus deposition were observed in the Duraflo II treated group, relative to the untreated control group, during the entire bypass period. The results suggest that despite high doses of circulating heparin in calves during CPB, the use of extracorporeal circuits with improved blood compatibility still provides measurable benefit. PMID- 2252776 TI - A blood-liquid interface for prolonged extracorporeal oxygenation with excellent antithrombogenicity. AB - The authors verified the excellent antithrombogenicity of a blood-liquid interface (BLI) and introduced an oxygenator based on the principle of gas exchange across direct BLI. In a newly developed oxygenator, three layers of liquid flowed horizontally, contacting one another: O2 saturated silicone oil on the top, O2 saturated fluorcarbon at the bottom, and blood in the middle. Gas exchange was carried out across both direct BLIs. This system provided excellent antithrombogenicity as well as good gas exchange. The results indicate that this method will become a promising modality for prolonged extracorporeal oxygenation. PMID- 2252777 TI - Rapid and precise whole blood protamine titration. AB - A rapid and precise whole blood protamine titration method was developed. The method uses azure A dye as the titration indicator and thereby replaces the tedious and time-consuming clotting assay with a facile colorimetric assay. The method provides the same accuracy in estimating the titration end-point, but allows the processing time to be shortened to that required by current clinical methods. The simplicity, flexibility, speed, and accuracy offered by the method, and the ability to use whole blood specimens for the measurements, should allow the method to be used by clinicians in the operating room or during a surgical procedure to estimate the adequate protamine dose required for heparin reversal. PMID- 2252778 TI - Evaluation of platelet damage in extracorporeal circuits using a visual platelet morphology method. AB - Platelet damage in extracorporeal circuits occurs as the result of contact with foreign surfaces, shear stress, gas interface, and other nonphysiologic conditions. A scoring method developed to determine platelet activation was modified for evaluating platelet damage in extracorporeal circuits. This method assigns a numerical score to platelet damage, as assessed by direct visualization with phase microscopy. Various commercially available blood oxygenators were tested by using a modified AAMI/ASAIO in vitro blood trauma protocol. Direct gas contact oxygenators showed a marked decrease in total platelet count and significant platelet damage. Platelet depletion and platelet damage were lower in membrane oxygenators than in direct gas contact oxygenators. Differences in platelet damage were observed between membrane oxygenators. The observed differences between devices demonstrate the influence of materials and hemodynamic design on platelet depletion and damage. The method developed allows quantitative evaluation of platelet damage caused by extracorporeal devices and is a sensitive indicator of lethal and sublethal trauma. PMID- 2252779 TI - Increase of intraplatelet free calcium ion during extracorporeal circulation with a hollow fiber oxygenator: arterial filter and dynamics of platelet thrombosis on oxygenator and filter in a pig model. AB - Intraplatelet free calcium (IPFC) ions provide a common pathway for platelet activation leading to thrombosis and embolization. IPFC levels were determined by chlorotetracycline fluorometry during extracorporeal circulation (ECC) with systemic heparin in eight Yorkshire pigs (weighing 30-40 kg; 3 control and 5 ECC); the ratio of slow phase organelle calcium sequestration to fast phase platelet-membrane binding is an index of free calcium. During 3 hr of ECC with a hollow fiber oxygenator (HFO) (Bentley CM-50) and AF (Bentley 1025), seven blood samples were collected 5 min before and during ECC. The platelet deposition (CPM/microCi) on HFO (PDHFO) was simultaneously measured with In-111-labeled autologous platelets (300-400 microCi) and a Geiger probe detector at -5, 0, 5, 30, 45, 60, 120, and 180 min. During ECC, IPFC and HFO thrombus increase significantly (p less than 0.05) at 45 min with respect to control IPFC values of 0.4 +/- 0.1, suggesting direct participation of calcium activated platelets in thrombosis on HFO. The decline of IPFC is due to extrusion and sequestration by dense granules, and decline in HFO thrombus is due to embolization. On the other hand, the embolus in the arterial filter was trapped in a linear fashion, with a consistent increase with time of ECC. PMID- 2252780 TI - Rapid platelet separation and collection for postoperative autologous transfusion. AB - The authors describe a technique for rapid, on-line, precardiopulmonary bypass separation and collection of 10-20% of a patient's platelets for storage and postoperative reinfusion. In a three stage process, blood is diverted through a hollow fiber hemofilter and platelets are concentrated near the fiber walls; the core is flushed of whole blood and the concentrated platelets are collected. Process mechanics were investigated in vitro with bovine blood; efficacy was studied with in vivo ovine experiments; and platelet function and viability were examined with in vitro human blood tests. Using commercially available hemofilters with 13,000 polyacrylonitrile fibers, the authors collected 1 x 10(11) to 2 x 10(11) platelets in 250 ml in 3.5 min. With fresh human blood, collected platelets exhibited normal morphology and aggregation response to adenosine diphosphate, collagen, and thrombin for 4 hours after collection. PMID- 2252781 TI - Maximum blood flow rates for arterial cannulae used in neonatal ECMO. AB - The arterial cannulae used in neonatal ECMO cause hemolysis and red blood cell damage at elevated blood flows. Hemolysis in extracorporeal circuits has been found to occur with shear stress greater than 132 dynes/cm2, turbulence as measured by Reynold's number greater than 1,000, and velocity greater than 120 to 200 cm/sec. These parameters need to be considered when sizing the proper arterial cannula for a required flow rate. In-vitro measurements of the pressure drop across six arterial cannulae at varying flow rates were performed using human blood with a hematocrit of 43%. Shear stress, Reynold's number, velocity, and pressure drop were calculated for each catheter at flow rates from 50 to 1,000 cc/min. The maximum mean flow rate to maintain the shear stress, Reynold's number, velocity, and pressure drop within the accepted range, was determined for each cannula. Recommended maximum blood flow rates for each of the six cannulae are given. Internal diameter, length, and cannula geometry appear to be the factors most affecting the flow achievable without causing red blood cell damage and hemolysis. Ten French Biomedicus, 10 French Cook, and 10 French Elecath arterial cannulae appear best suited to deliver the range of blood flow rates used in neonatal ECMO. PMID- 2252782 TI - Protection of the small intestine against irradiation by means of a removable prosthesis. AB - In radiation therapy of tumors, several techniques are used to prevent injury of the intestinal loops. Their purpose is to drive the intestine out of the external beam. Understanding the disadvantages they present, a temporary prosthesis which effectively protects the small bowel, and is easy to remove, has been developed. The device is a 600 to 1,000 ml, silicone rubber, expandable balloon. When implanted in the pelvis or retroperitoneal cavity, and filled, this balloon displaces the intestinal loops out of the pelvic irradiation field. It may remain either filled or empty between each irradiation session. Due to its particular elliptical shape, once empty, the balloon can be removed through a 3 cm incision under local or peridural anesthesia at the completion of radiotherapy. Eleven patients with recurrent (8) or primary (3) cancer have been implanted. The protective effect has been evaluated on successive biologic tests, performed during treatment. No problem related to the prosthesis, no alteration of the biologic tests, nor bowel injury have been observed after several months follow up. This device is suitable for preventing intestinal complications during therapy, allowing a higher dose of radiations in some cases. PMID- 2252783 TI - Improvements in determination of cardiac output with a Swan-Ganz catheter. AB - The time constant for heat transfer may affect exact determination of cardiac output with Swan-Ganz catheters. Commercially available Swan-Ganz catheters are provided with thermistors with varying time constants. Current monitoring of cardiac output is not corrected for these time constants, so the conventional method of determining cardiac output using the equation of Stewart-Hamilton produces marked errors. The authors propose a new method of determining cardiac output with Swan-Ganz catheters with varying time constants from thermal dilution curve data based on Newton's cooling law. Values for blood flow rate determined by the new method using a completely stirred tank of original design, mimicking the natural heart and using bovine blood, are almost the same as values observed at varying saline infusion volumes, saline temperatures, and saline infusion times. PMID- 2252784 TI - Sensitivity of the Azure heparin assay and comparisons with activated clotting time and whole blood partial thromboplastin time. AB - In order to compare the Azure A Assay to other commonly accepted measures of heparinization, samples of fresh donor sheep blood were prepared with known levels of heparin between 0 and 9 U/ml. For each sample, two determinations of the Activated Clotting Time (ACT) and Whole Blood Partial Thromboplastin Time (WBPTT) were performed. Similarly, an Azure A Assay standard curve of absorbance versus heparin concentration was constructed for the same blood. Three replicates of the procedure were performed, and the average relative error in each assay was computed as the 95% confidence interval on the regression line divided by the slope of the regression curve. Parallel studies were also performed to assess the effect of various plasma constituents on the Azure Assay. Results indicate that all of the assays are equally accurate for heparin levels at or below 2 U/ml, while the ACT and Azure assays are equivalent at heparin levels near 4 U/ml, but the WBPTT is not usable at concentrations above 2 U/ml. The Azure Assay is not sensitive enough for very low heparin levels (less than 1 U/ml), but it is quite accurate and, indeed, is the only rapid assay for heparin concentrations higher than 4 U/ml. In the sensitivity studies, variations in albumin levels and plasma platelet count were shown to have a significant effect on the accuracy of the Azure assay, whereas calcium levels had no effect. PMID- 2252785 TI - One year of rHuEPO therapy prolongs RBC survival and may stabilize RBC membranes despite natural progression of chronic renal failure to uremia and need for dialysis. AB - rHuEPO was administered to eight patients with chronic renal failure (CRF) and uremia (U) for 1 year. Creatinine Clearance (GFR) averaged 14.3 (9-25) ml/min at an Hct of 28% (26-30). Baseline RBC survival by 51Cr T1/2 was highly correlated with GFR (r = 0.66), p less than 0.05 (2), average 21.6 days. Repeat 51Cr T1/2 at 3 months with GFR 10 ml/min at Hct 38% was prolonged by 7 days to 28.6 (p less than 0.005), and at 1 year remained increased to 28 days (p less than 0.001) with Hct 39%, despite further decreased GFR to less than 4 ml/min and need for dialysis. Reticulocytes varied from 1.6% to 7.4 (3-6 weeks) to 3.1 (3 months) and 1.5% (1 year). Bone marrow cellularity increased from 36% to 47% (3 months) and 44% (1 year). M:E ratio decreased from 3.9:1 to 1.7:1 (3 months) to 1.6:1 (1 year). Marrow iron decreased from 4.1/6 to 2.4/6 (3 months) to 1.8/6 (1 year). Doses of rHuEPO had to be reduced to avoid polycythemia. rHuEPO stimulates erythropoiesis in pts with progressive CRF and U for 1 year. The initial increase in hematocrit is due to the early peak of reticulocytes. At 3 months, rHuEPO maintains the increased hematocrit by three mechanisms: 1) increased reticulocytosis, 2) a trend to increased bone marrow erythroid cellularity, and 3) lengthened RBC survival. At 1 year of rHuEPO therapy, the trend to increased marrow cellularity persists, however, the maintenance of target hematocrit is via a lengthened RBC survival. Despite progression of CRF and U, rHuEPO produced RBCs with longer survival than expected. RBC membranes may have been stabilized by rHuEPO. PMID- 2252786 TI - Change in intracellular calcium ions during shear induced platelet aggregation. AB - The authors have developed a method to measure intracellular calcium ion concentration ([Ca2+]i) during shear-induced platelet aggregation. A cone and plate viscometer was adapted for continuous recording of both light transmission and fluorescence intensity. Citrated platelet rich plasma was incubated with Indo 1AM at a concentration of 10 microns for 30 min at 37 degrees C, then applied to the albumin density gradient to prepare washed platelets. To Indo-1AM loaded washed platelets, fibrinogen, and von Willebrand factor (vWf) were added, with 1 mM CaCl2. Platelets were then exposed to changing shear stress (6-108 dynes/cm2) for simultaneous measurement of aggregation and [Ca2+]i. [Ca2+]i in resting platelets was estimated as approximately 100 nM. At low shear stress (10-20 dynes/cm2), [Ca2+]i did not change. In contrast, a marked increase in [Ca2+]i was observed concurrent with aggregation at high shear stress (100-108 dynes/cm2). However, no increase was seen in the presence of 1 mM EGTA. The increase was prevented by monoclonal antibodies against GPIb or vWf, which inhibited vWf binding to GPIb. A monoclonal anti-vWf antibody, which inhibited vWf binding to the GPIIb/IIIa complex, did not affect [Ca2+]i increase during high shear induced platelet aggregation. These results suggest that binding of vWf to GPIb may trigger Ca2+ influx. PMID- 2252787 TI - Oral anticoagulation in patients with ventricular assist devices. AB - Nine men aged 25-63 years (mean 42 years) received pulsatile ventricular assist devices (VADs) as a bridge to cardiac transplantation. Duration of support ranged from 8-266 days (mean 70.7 days); seven patients (pts.) were bridged with a LVAD and two received BVADs. All pts. were maintained on oral anticoagulants after initial intravenous (IV) heparin or dextran therapy. During warfarin therapy, supplemental IV heparin was used only if the prothrombin time fell below 1.5 times control (approximately 30% activity). In 639 days of support, there was one thromboembolic event due to mechanical failure, and one pt. had thrombus in the VAD which did not embolize. PMID- 2252788 TI - LVAS pump performance following initiation of left ventricular assistance. AB - Prevention of disturbed flow (e.g., flow stasis) and consequent thrombosis in heart pumps is based upon design characteristics determined during laboratory bench tests. These tests employ optimal filling and emptying characteristics, such as the full-fill to complete empty mode in the Novacor left ventricular assist system. Filling characteristics of the Novacor LVAS were examined during the first 48 hours after implantation in 14 patients. Fill volume of the pump was reduced in pathologic states, such as cardiac tamponade, and following the initiation of right ventricular mechanical circulatory support. In addition, multiple regression analysis revealed that right ventricular function measured by the amount of inotropic support required, the right ventricular ejection fraction, and the total pulmonary resistance, significantly predicted left ventricular assist pump fill volume during the first 48 hours of support. Flow visualization simulating these clinical conditions of incomplete filling suggest inadequate valve washing, particularly around the inlet valve and its conduit, which may predispose to thrombus formation. PMID- 2252789 TI - Clinical use of the Berlin Biventricular Assist Device as a bridge to transplantation. AB - The Berlin Artificial Heart System/Biventricular Assist Device (BVAD) was used in 38 patients. 1) Twenty-eight patients were awaiting cardiac transplantation (Tx) (age 23-56 yrs). All patients had contraindications not allowing immediate Tx. 2) Five patients were emergency cases not on our Tx list (postcardiotomy cardiac failure, acute myocarditis) (age 28-59). 3) Five patients were post Tx patients with graft failure (age 22-52). Extracorporal circulation was used for implantation of the BVAD. In group 1, 21 of 28 patients (pts) recovered, and all were subsequently transplanted after 6 hours to 39 days, when all organ function was restored. In 7 pts, mechanical circulation was terminated after 1-40 days because of further deterioration. Five of the transplanted pts died, 14 pts survived (greater than 30 days), and 2 pts were just transplanted with satisfactory postoperative courses. Of group 2 and 3 pts, two were successfully weaned. In one patient the allograft recovered after 11 days of support. PMID- 2252790 TI - Multi-institutional evaluation of the Tokyo University Ventricular Assist System. AB - A total of 61 VASs developed in Tokyo University were evaluated at 21 institutions in the period 1985-1989 for determination of its reliability and effectiveness. The system is comprised of a pneumatic sack-type pump (Nippon Zeon Co.), and its driving console (Aishin Seiki Co.). The stroke volume of the pump is 40 ml and blood contacting surfaces are coated with Cardiothane. Ages of the patients (pts) ranged from 12-82 yrs (mean 58 yrs). VASs were used in the assist mode of LVAD (54 pts), RVAD (5 pts) and BVAD (2 pts). Most of the cases (58 pts) included postocardiotomy cardiogenic shock after surgery for ischemic (28 pts), valvular (22 pts), both ischemic and valvular (7 pts) and congenital (1 pt) heart diseases. Average duration of the assist ranged from 1 hr-20 days (mean 5.6 dys). The VADs could be weaned in 34 cases (56%) and among these, 13 cases (21%) survived to discharge from the hospital. Causes of death in cases which could be weaned from the VAD included multiple organ failure/due to delayed institution of adequate circulatory support, renal failure and systemic infection. Small and minute thrombus formations were noted in 7 cases however, no pump originated thromboembolism were complicated. No troubles of the pump including leakage nor breakage, no mechanical failures of the driving consoles were experienced in any of the cases. Thus, it is concluded that the system was proved to be clinically effective and reliable. PMID- 2252791 TI - Thrombus in a natural left ventricle during left ventricular assist: another thromboembolic risk factor. AB - Systemic thromboembolism is one of the serious complications during use of a left ventricular assist system (LVAS). The authors' original LVAS has excellent antithrombogenicity to reduce this risk, but thrombus formation in a natural left ventricle (LV) is another risk factor for systemic embolization. We used our LVAS in 22 patients. Of these, LV wall motion was studied in 15, and a smoke-like echo disclosed thrombus in the LV in eight. When LVAS sufficiently supported the systemic circulation, LV wall motion was irregular upon closure of the aortic valve. Upon recovery of LV function and decrease of LVAS flow, the smoke-like echo diminished and LV thrombus decreased in one, but LV thrombus remained unchanged or increased in seven. Systemic administration of antithrombotic agents had an unclear effect. Seven of eight patients with LV thrombus on echo died during or after LVAS. In these seven, a high incidence of LV thrombus (71%), and systemic embolism to the brain (29%) or kidney (86%), were revealed at necropsy. We subsequently used local heparinization to prevent LV thrombus formation. One patient with a smoke-like echo had no evidence of LV thrombus or systemic embolism. During LV assist, careful management of the LVAS, and intra-LV heparinization should be considered to reduce the risk of thrombus formation in the natural LV. PMID- 2252792 TI - Effect of beta cell distribution on the performance of a bioartificial pancreas. AB - The insulin response of available prototype hollow fiber bioartificial pancreas devices remains unacceptably slow. Although previous experimental and theoretical investigations provide insight into the factors governing the performance of these devices, there are currently no results on the effects of beta cell distribution on insulin response. The authors have developed a detailed theoretical model for insulin response in a hollow fiber bioartificial pancreas. Model predictions have been shown to be in good agreement with literature data on the insulin release from an in vitro hollow fiber device. In this study, model simulations were used to evaluate the effects of axial and radial variations in beta cell density on the insulin response. For a device with no convective recirculation (i.e., a diffusion controlled device), the radical distribution of cells in the matrix and shell plays a critical role in determining device response, but the insulin response is essentially independent of the axial beta cell distribution. In contrast, for a device with substantial recirculation, there is a very strong dependence on the axial beta cell distribution, with a weaker dependence upon the radial distribution. These results clearly demonstrate the potential importance of beta cell distribution in the analysis of in vivo and in vitro experimental data, and in the design of effective clinical devices. PMID- 2252793 TI - An implanted peritoneal oxygen tonometer that can be calibrated in situ. AB - Oxygen tension in the peritoneum has been continuously measured with a Silastic tonometer having an integral oxygen electrode and inlet and outlet tubes for gasequilibrated electrolyte solution. Remote kinetic calibration of the system is periodically performed. Tonometers were implanted in six rabbits. Peritoneal oxygen tension was measured in awake and anesthetized rabbits under various oxygen breathing conditions. PMID- 2252794 TI - Effect of a leukocyte-platelet removal filter on ischemia induced reperfusion injury. AB - The effect of leukocyte and platelet depletion on reperfusion injury using a leukocyte-platelet removal filter (LRF) in intracoronary thrombolysis is reported. To better define the usefulness of LRF in evaluating the effectiveness of intracoronary thrombolysis with this device, several cardiovascular variables were examined in rabbits during ischemia followed by reperfusion. The rabbits underwent cytoapheresis with LRF (n = 5) and were compared with controls without LRF (n = 5). LRF was composed of a nonwoven polyester fabric (1.8 microns, 4.6 gm). Removal of leukocytes and platelets by LRF was 98% for both. A period of 30 min equilibration was allowed before any experimental intervention, at which time the diagonal artery was occluded for 20 min and then reperfused. All arrhythmias were defined and quantified in accordance with the Lambeth Convention. Regional wall thickening was examined by a pulsed Doppler dimension system. No significant differences were observed in hemodynamic variables between the two groups; however, rabbits treated with a LRF demonstrated greater regional wall thickening (LRF group: 17 +/- 0.9%, control group: 11 +/- 0.3%, p less than 0.01), as well as significant improvement in the frequency of ventricular arrhythmias (LRF group: 12.5%, control group: 47.2%, p less than 0.01). The data suggest that LRF may help prevent arrhythmias, and preserve left ventricular contraction, during and after intracoronary thrombolysis. PMID- 2252795 TI - A high density culture of hepatocytes using a reticulated polyvinyl formol resin. AB - To enable high density culture of hepatocytes to be used as a hybrid artificial liver support or bioreactor system, collagen coated reticulated polyvinyl formal (PVF) resin (a filter material with a porosity of more than 80%) was used for the primary culture of hepatocytes. Stationary and perfusion culture experiments using PVF resin and monolayer culture were performed as control experiments. Due to the porous structure of the substrate material, hepatocytes were able to penetrate the reticulated pores of the PVF resin, and adhere to and spread on its surface. The densities of hepatocytes attained with PVF were about 10 times as high as those in the monolayer culture using conventional collagen coated Petri dishes. Hepatocytes immobilized in the PVF resin showed viability, as assessed by glutamic pyruvic transaminase (GPT) activity in the medium. Perfusion culture with PVF resin showed stable, high level metabolism, ammonium removal, and urea secretion comparable to the monolayer culture. It is concluded that perfusion culture with PVF resin is useful in attaining a high density culture of hepatocytes. PMID- 2252796 TI - Pore size and temperature effects in membrane separation of albumin from immunoglobulins. AB - A series of ethylene-vinyl alcohol co-polymer hollow fiber membranes, differing in maximum pore diameter (0.01, 0.02, 0.03 micron), in modules of 2 m2 total surface area, were evaluated for separation of immunoglobulins G and M (IgG and IgM) from albumin (Alb) in normal human plasma at two different temperatures (4 degrees C and 37 degrees C). Separation was based on molecular size differences. In the dead end mode, with constant flow rate (20 ml/min) filtration, nearly total recovery of Alb, 27% rejection of IgG, and 87% rejection of IgM at VT = 2.4 L (total volume of filtrate accumulated at transmembrane pressure delta p = 300 mmHg) was observed for the largest pore membrane at 37 degrees C. A significant increase in IgG rejection to 50% was observed at 4 degrees C for this membrane, with a concomitant decrease of VT to 1 L. Average rejection coefficients of representative solutes, and delta p dependence on filtrate volume, were analyzed using the log-normal regression method and membrane pore blocking models. Filtration characteristics were noted to be dominated by the native membrane properties at 37 degrees C, and by solute-solute and solute-membrane interactions at 4 degrees C. PMID- 2252797 TI - Development of a small caliber biologic vascular graft: evaluation of its antithrombogenicity and the early healing process. AB - The authors previously showed that a small caliber xenograft using our crosslinking technique was applicable to aortocoronary bypass grafting. In this study of the graft, the antithrombogenicity and healing process was evaluated at an early stage after implantation. Fresh sheep carotid artery (3mm ID) was obtained and cross-linked with polyepoxy compounds, and then used as a small caliber vascular graft. The graft was white and soft. Six cm segments of the graft were implanted into the carotid arteries bilaterally in nine dogs. Sodium heparin was given during the surgery, but no anticoagulant was used postoperatively. Fifteen grafts from eight dogs were removed from 1 hr to 30 days after implantation, and 13 of 15 grafts were found to be patent. Two grafts, one at 3 days, and the other at 14 days, were occluded. The anastomotic area of the occluded grafts felt hard when touched from the outside. In one dog, the grafts were shown angiographically to be patent at 14 days after implantation, and this dog was kept for long-term observation. Macroscopically, no thrombus was observed on any of the patent grafts. Microscopically, the inner surface near the anastomotic lines was covered with endothelial cells, and infiltration of fibroblasts was observed from the outside 7 days after implantation. No foreign body reactions were seen around the graft. After 30 days of implantation, a thin layer of plasma protein at the middle of the graft was observed by scanning electron microscopy (SEM). From these observations, it was concluded that the grafts exhibited satisfactory early antithrombogenicity and healing after implantation. PMID- 2252798 TI - Proliferation and substrate effects on endothelial cell thrombogenicity. AB - The effects of the cellular differentiation status and the adhesive-substrate on endothelial cell function in cell culture were measured with an enzyme based assay of surface thrombogenicity. A solid plastic, microporous polymeric, and fibronectin (FN) treated microporous polymeric were used as substrates for growth of endothelial cells. The microporous and FN treated synthetic substrates have been shown to aid in the induction of cellular differentiation mechanisms. Cells were studied under proliferative and nonproliferative growth conditions. The thrombogenicity of the surface created by the endothelial cell monolayers under various experimental conditions was determined using an enzyme based assay of fibrin deposition. Actively proliferating cells on the solid plastic substrate produced the most thrombogenic surface, while confluent endothelial cell monolayers grown on FN treated microporous substrate were the least thrombogenic surfaces. These data suggest that endothelial cell surface thrombogenicity is under substrate control, and also related to the cellular differentiation status. These findings are being used to design a novel approach to the small diameter synthetic vascular graft problem. PMID- 2252799 TI - Substrate effects on endothelial cell adherence rates. AB - Endothelial cell attachment to a synthetic substrate was studied using an in vitro model system. Attachment rate was defined as the number of tritium-labeled endothelial cells attached to a synthetic substrate after 30 minutes. The surface of the synthetic substrate was chemically modified with either laminin or fibronectin. Labeled endothelial cells attached more rapidly to synthetic substrate, chemically modified with biomolecules, as compared with the untreated substrate controls. Unlabeled endothelial cells were grown to confluency on a second set of modified and untreated substrates. The cells were removed with 1% Triton, and the rate of re-endothelialization with tritium-labeled endothelial cells was determined. The rate was 11-13 times that of the same cells on untreated substrate. These data confirm that biomolecules increase the attachment rate of endothelial cells to synthetic substrate, and also suggest that endothelial cells may secrete a Triton-insoluble product (Sigma, St. Louis, MO) into subendothelial matrix that increases re-endothelialization. PMID- 2252800 TI - Effect of complement and arachidonic acid pathway inhibition on white blood cell count and deposition on vascular grafts. AB - To determine the role of complement and arachidonic acid metabolites in the decrease in peripheral white blood cell count (pWBC) observed with graft implantation, Dacron aortic grafts were implanted in control rabbits (Group I, n = 13), or rabbits pretreated with cobra venom factor (80 U/kg) to deplete complement (Group II, n = 13), indomethacin (2.5 mg/kg) to inhibit cyclooxygenase (Group III, n = 7), or diethylcarbamazine (DEC, 90 mg/kg) to inhibit leukotriene synthesis (Group IV, n = 7). pWBC was measured 15 min and 1 hr after graft implantation. After graft removal, the WBC count on grafts (gWBC) was determined by light microscopy (LM) and scanning electron microscopy (SEM). One hr after graft implantation, pWBC decreased significantly in Groups I-IV to 46%, 52%, 40%, and 45% of preoperative pWBC, respectively. There was no significant difference among the groups. LM revealed gWBC per 63x field of 8.0, 12.3, 5.8, and 6.8 in Groups I-IV, respectively. Similarly, SEM showed gWBC per 2000x field of 2.5, 5.6, 0.7, and 1.5 in Groups I-IV, respectively. SEM gWBC was significantly greater in Group II than I (p less than 0.01), and significantly less in Group III than I (p less than 0.05). Results suggested that complement and arachidonic acid pathways alone do not affect the fall in pWBC, but may influence gWBC. PMID- 2252801 TI - The dynamics of platelet thrombus formation rate, thrombus retention time, and rate of embolization on a control and heparin bonded polyurethane angio-catheter. AB - The dynamics of platelet deposition and embolization from control and heparin bonded polyurethane catheters (CPC and HBPC) was evaluated with In-111 labeled autologous platelets (IN-PLT) and a computerized gamma camera (CGC). Ten non heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis) 24 hr after injection of 300-420 microCi of In PLT, and imaged for 3 hr with the computerized gamma camera. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the curves were analyzed for early rate of thrombus formation (upswing), thrombus retention time (full width at half maxima of the RPDC-peak), and rate of embolization (downswing) on both catheters. The four parameters (mean +/- SD) of thrombosis on catheters and integral of the radioactivity time curve for the 3 hr duration of imaging were calculated from normalized counts/sec. The rate of thrombus formation and rate of embolization are higher for the control than HBPC, suggesting that heparin-bonding decreases the early rate of thrombosis and embolization. The thrombus adhesivity and retention time appear shorter for the control catheter, indicating that the control thrombogenic catheter forms multiple thrombi and emboli than HBPC. The integral appears larger for the control catheter than HBPC. In vivo (dynamic) studies, in vitro studies, and critical analyses of the radioactivity time curve were essential for complete evaluation of thrombogenicity of catheters and other cardiovascular prostheses. PMID- 2252802 TI - Recombinant human erythropoietin does not increase clotting in vascular accesses. AB - The incidence of vascular access clotting was evaluated over 5.25 years. The first 32 months served as a control period. During the second period of 31 months, recombinant human erythropoietin (epoetin) was used for an average duration of 13 months (range, 2-32 months) in 79 patients. The overall incidence of vascular access clotting decreased from a monthly rate of 0.06 to 0.03 events per patient-month over the 5 year period. Distribution of the number of events per patient did not differ between the two periods, with 55% to 60% of patients having no clotting episode. Patients with recurrent clotting (two or more events) accounted for 68% of episodes. During the second period, there were no differences in the incidence of vascular access clotting in epoetin treated patients vs untreated patients (0.38 events per patient-year vs. 0.46 events per patient-year, both slightly lower than in period 1 [0.52 events per patient year]). It is concluded that epoetin does not increase vascular access clotting. PMID- 2252803 TI - Venturi grafts for hemodialysis access. AB - Vascular access grafts can produce venous and puncture site stenosis, and excessive shunted flow. A vascular access graft that controls the shunted flow at 500-650 ml/min by venturi flow resistance, and offers the potential for reduced venous stenosis, is presented. Twelve venturi grafts consisting of 6 mm ePTFE, with a thermally formed venturi resistance, were implanted in a canine femoral arterio-venous (A-V) model and cannulated for simulated dialysis for periods up to 6 months. Pressures, bleeding times, and puncture site healing were compared at sites upstream and downstream of the venturi. Nine 6 mm ePTFE grafts were implanted as controls. Venturi and control graft patency rates were similar: 90% for venturi grafts and 89% for control implants at 4 months. Measurements verified pressure dissipation by the venturi from 85 to 15 mmHg, delivering near normal pressures to the vein; downstream pressures were 22 mmHg higher in controls. Sites downstream of the venturi did not bleed at 4 min, whereas bleeding was often noted after 9 min at other sites. Puncture sites upstream of the venturi had less stenosis and less mural thrombus than sites downstream of the venturi, and compared favorably with puncture sites in the control grafts. This improved healing and low pressure delivery to the vein may offer clinical advantages. PMID- 2252804 TI - Performance of a longitudinally compliant PTFE vascular prosthesis in an ovine A V fistula model. AB - Nine chronic implants of 6 mm diameter vascular grafts were performed in an ovine model to compare the performance of the longitudinally compliant Ultraflex PTFE Plus vascular prosthesis with that of the Gore-Tex reinforced expanded polytetra fluoroethylene (PTFE) graft. Implants were performed in the sheep neck as right carotid to left jugular arterio-venous (A-V) grafts. Grafts were explanted after 6 months unless they occluded earlier. The Ultraflex graft demonstrated superior handling characteristics during implant. Patency rate at 6 months was 60% (three of five) for the Ultraflex graft (experimental graft by Baxter Edwards, CVS Division, Irvine, CA), and 25% (one of four) for the Gore-Tex graft (WL Gore & Associates, Inc., Flagstaff, AZ). The Gore-Tex prosthesis had more calcification of the graft wall. PMID- 2252805 TI - Dynamic internal compliance measurements of fresh and fixed artery. AB - A new device is used to compare dynamic internal compliance of biologic vascular prostheses derived from bovine artery. These grafts were prepared using dialdehyde starch (DS), and a polyepoxy polyether compound (PC), as crosslinking agents. Internal compliance was measured using the Dynatek DCT1 Dynamic Compliance Tester, developed by Dynatek Laboratories. This device utilizes a variable speed DC motor coupled to miniature bellows, which displace a stroke volume controllable to within 0.5 microliter. The bellows displace fluid into and out of the graft, resulting in a sinusoidal change in internal pressure. Volumetric displacement is monitored by a linear voltage displacement transducer (LVDT) mounted on the motor coupling, whereas internal graft pressure is monitored by a miniature pressure transducer mounted on the closed end of the graft. For this series of experiments, a pressure range of 80-120 mmHg was used, with a cycle speed of 80 cycles/min. Preliminary results indicate that PC fixation of bovine artery results in a vascular graft with internal compliance somewhere between fresh tissue and DS fixation. This data confirms qualitative assessment. The DCT1 provides valuable comparative information on the dynamic internal compliance of vascular prostheses. These measurements reflect what occurs in the graft lumen, since they take into account wall compression and axial deformation. Further development is required to separate radial and longitudinal compliance components. PMID- 2252807 TI - The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro. AB - To examine the effects of T3 on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated 45Ca. The effects of T3 were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T3 had a biphasic effect. At high concentrations (10(-5) M-10(-6) M) T3 inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while 45Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T3, at lower concentrations (10(-7) M-10(-9) M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. 45Ca release was significantly decreased at these concentrations. Neither T3 nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T3 has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T3 stimulates bone resorption in a way similar to PTH. PMID- 2252806 TI - Suppression of immunoglobulin and interleukin-6 production from peripheral blood mononuclear cells by dialysis membranes. AB - The influence of dialysis membranes on immunoglobulin and interleukin-6 production was estimated in vitro. Peripheral blood mononuclear cells from 11 patients undergoing hemodialysis were incubated for 7 days on Cuprophan, Hemophan, and polyacrylonitrile flat sheet membranes. IgG, IgA, IgM, and IL-6 were assayed in the supernatants with the aid of enzyme-linked immunosorbent assay (ELISA) techniques. Pokeweed mitogen-stimulated IgG production declined significantly from 319 +/- 40 ng/ml on polystyrole to 162 +/- 26 ng/ml on Cuprophan; 135 +/- 25 ng/ml on Hemophan; and 109 +/- 20 ng/ml on polyacrylonitrile. A similar pattern was observed for IgA and IgM production. IL 6 production was significantly reduced in the presence of Cuprophan (151 +/- 45 pg/ml), Hemophan (167 +/- 6 pg/ml), and polyacrylonitrile (108 +/- 33 pg/ml) when compared with polystyrole (724 +/- 34 pg/ml). It was concluded that the long-term exposure of mononuclear cells to artificial surfaces during dialysis may contribute to the impaired humoral response observed in dialysis patients. This effect may be due to a decline in B cell stimulation by monocytes, a possibility suggested by the reduction in monocytic IL-6 production. PMID- 2252808 TI - Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. AB - 5,5-diphenylhydantoin (Phenytoin, PHT), a widely used anticonvulsant, is also a vitamin K antagonist and disrupts bone metabolism, leading to osteomalacia. The vitamin K-dependently synthesized protein, osteocalcin, has been implicated as a key regulatory protein in bone resorption. The purpose of the present study was to determine whether PHT had an effect on osteocalcin secretion. Cells were grown to confluence in Ham's F-12 nutrient mixture, and treated with 1,25 (OH)2 vitamin D3 (2.6 microM to 2.6 pM) or PHT (5-100 micrograms/mL) for either 24 or 48 h of pretreatment. The media were then discarded, replaced with fresh media and test reagents, and quantitated for osteocalcin by radioimmunoassay at 0, 4, and 8 h secretion time points. Results were statistically analyzed by the Student's two tailed t test. Controls showed a nearly linear secretion rate of osteocalcin, reaching 8-9 ng/10(6) cells by 8 h. Vitamin D3 (2.6 nM) maximally stimulated secretion nearly two-fold after 24 or 48 h of pretreatment in comparison to controls. PHT alone (25-100 micrograms/mL) exerted an inhibitory effect, which appeared dose-dependent and was most evident at 4 and 8 h. PHT (50 micrograms/mL) had a significant effect, in the presence of a range of vitamin D3 concentrations (2.6 microM to 2.6 pM), after 48 h of pretreatment. A maximal PHT dose of 100 micrograms/mL had no effect on either the viability or the numbers of cultured cells. These data indicate that PHT affects osteocalcin secretion from osteoblastic rat osteosarcoma (ROS 17/2.8) cells. PMID- 2252809 TI - Effects of low doses of strontium on bone quality and quantity in rats. AB - Strontium (Sr) has been shown to increase bone mass when given at low doses. In this study, the diets of rats containing 0.50% calcium were supplemented with Sr (0.19 and 0.40% of SrCl2 orally) for periods of four and eight weeks. Long bones and vertebrae were studied by density fractionation and each fraction was analyzed chemically. X-ray diffraction was used to determine crystal size. Static and dynamic histomorphometric parameters of bone formation were also measured. We found a shift towards lower density in the mineralization profiles of Sr supplemented rats (0.40%), as well as a decrease in bone crystal size at the larger dose of Sr. The CO3 content and the Ca/Sr ratio of the bone decreased with increasing Sr content. We found an increase in the vertebral trabecular bone volume together with an increase in osteoid volume in Sr supplemented rats. This study shows that Sr at the larger dose induces bone hypomineralization as well as an increase in bone mass in rats fed a relatively low calcium diet. PMID- 2252810 TI - Long-term fatigue behavior of compact bone at low strain magnitude and rate. AB - Fatigue behavior of compact bone at physiological strain ranges was examined in vitro. Standardized specimens of bovine compact bone were cyclically loaded in uniaxial tension of 0-1200 or 0-1500 microstrain for up to 13-37 million cycles to study the long-term fatigue properties. All specimens exhibited fatigue during the first several million cycles of loading, evidenced by a gradual decrease of specimen modulus during this initial loading period; mean modulus loss for all specimens was approximately 6%. After this initial stiffness loss, specimen modulus stabilized and did not change again for the duration of the loading. Osteonal bone specimens lost significantly more stiffness than primary bone specimens during the early loading history, but neither microstructural type progressed to fatigue failure. These data suggest that some fatigue of compact bone is a realistic expectation of the normal loading environment, but this fatigue does not progress to fatigue failure within a physiologically reasonable number of cycles when tested in vitro at strain magnitudes like those measured in living animals. Implications for fatigue/stress fractures in vivo are discussed. PMID- 2252811 TI - Enzyme cytochemical localization of alkaline phosphatase in cultures of chondrocytes derived from normal and rachitic rats. AB - Epiphyseal growth plate cartilages were removed from rats which had been maintained on normal laboratory chow or a rachitogenic diet. Chondrocytes were released from the growth plates by collagenase digestion and cultured in tissue chamber slides. After 7, 10 and 12 days of culture, the chondrocytes were removed as intact multilayers and processed for electron microscopical enzyme cytochemical studies. Alkaline phosphatase activity in the cultures was visualized by means of a cerium based capture method. Electron-dense cerium phosphate deposits were localized on the membrane of matrix vesicles and plasma membranes of chondrocytes derived from normal and rachitic animals. The appearance of first crystals within matrix vesicles was characterized by a concomitant decrease in alkaline phosphatase activity in the membrane of these structures. Calcification was initiated at approximately the same time in cultures of chondrocytes derived from normal or rachitic animals. The results suggest that rickets has no serious effects on the capacity of chondrocytes to support matrix calcification in vitro. Additionally, the evidence indicates that alkaline phosphatase-positive matrix vesicles play a significant role in the initiation of this process. PMID- 2252812 TI - Transient effects of subcutaneously administered prostaglandin E2 on cancellous and cortical bone in young adult dogs. AB - The transient effects of prostaglandin E2 (PGE2) on cancellous and cortical bone in iliac crests and mid-tibial shafts of nine intact young adult dogs were evaluated following 31 days of treatment. Histomorphometric bone changes were characterized from in vivo fluorescent double-labeled undecalcified bone specimens. PGE2 caused an increase in cancellous bone remodeling evidence by increased in activation frequency; increased percent eroded and formation surfaces; increased mineral apposition and bone formation rates; and shortened resorption, formation, and total bone remodeling periods. Activated cancellous bone remodeling did not lead to decreased cancellous bone mass, indicating an imbalance between bone resorption and formation in favor of formation (activation ---resorption----stimulated formation; A----R----F increases) at remodeling sites. The PGE2 treatment activated bone modeling in the formation mode (activation----formation; A----F) at the periosteal and endocortical surfaces and increased activation frequency of intracortical bone remodeling in the tibial shaft. Increased modeling activation converted quiescent bone surfaces to formation surfaces with stimulated osteoblastic activity (i.e., increased percent labeled periosteal and endocortical surfaces, mineral apposition rates, and woven and lamellar trabecular bone formation) leading to 9- to 26-fold increases in newly formed bone mass in subperiosteal, subendosteal, and marrow regions, compared to controls. However, increased intracortical bone remodelling elevated remodeling space (i.e., increased cortical porosity), producing a bone loss that partially offsets the bone gain. The combined events lead to a positive bone balance in PGE2-treated cortical bone, compared to a negative bone balance in control bones. Collectively our data suggest that in vivo PGE2 is a powerful activator of cancellous and cortical bone formation, which may be able to build a peak bone mass to prevent and/or correct the skeletal defects to cure osteoporosis. PMID- 2252813 TI - Vitamin D status among patients with fractured neck of femur in Hong Kong. AB - Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control. PMID- 2252814 TI - Changes in mast cell number during the activation phase of an induced synchronized remodeling sequence in the rat. AB - Increase in mast cell (MC) number has been reported in some pathological conditions with increased remodeling. However, it is not known whether MCs are involved in the physiological remodeling of bone. In the present study the possible variations in MCs were investigated during the activation phase in a rat model of synchronized remodeling. Seven groups of 10 rats were used. As early as the first day of induction, MCs increased by 50% and then decreased on day 2. The same pattern of changes recurred on days 3 and 4. Intact non-degranulating MCs increased mainly at some distance from the bone surface. Degranulating MCs conversely decreased near the cambium layer of the periosteum. Prostaglandins were not involved in these changes. These results suggest an association between the events leading to the onset of bone resorption and MCs. Degranulation might induce the release of agents active on these events. PMID- 2252815 TI - [Theme: hand hygiene--hand hygiene campaign 1990]. PMID- 2252816 TI - [Cleaning, disinfection and sterilization of anesthesia equipment]. PMID- 2252817 TI - [Rehabilitation. Systematic exercising of stroke patients in a cross-professional environment]. PMID- 2252818 TI - ["Alternative" nurse. Acupuncture in the hospital]. PMID- 2252819 TI - [Rehabilitation. Teaching model for patients with heart infarct]. PMID- 2252820 TI - [Care of the aged. Handling of drugs in old age and nursing homes]. PMID- 2252822 TI - [A different viewpoint: illness as a possibility for development]. PMID- 2252821 TI - [The frail elderly--I am not sick, I am only old]. PMID- 2252823 TI - [HIV infection and AIDS--hygiene and AIDS]. PMID- 2252824 TI - [From the patient's world. Residents shall have disposal over their own days]. PMID- 2252825 TI - [From the patient's world. No changes without acting--expression therapy for psychotic women]. PMID- 2252826 TI - [From the patient's world. Can we stop the supply of food and water?]. PMID- 2252827 TI - [From the patient's world--he is cheerful when he chats and fools around with us!. Interview by Bente Ramholt]. PMID- 2252829 TI - [Farmers should also take care of their health!]. PMID- 2252830 TI - [Establishing standards in nursing of cancer patients]. PMID- 2252828 TI - [Pharmacology (2). Chemotherapy]. PMID- 2252831 TI - [Registration of nursing resources. Staffing for the future. Intensive care staffing in the neonatal department]. PMID- 2252832 TI - [From the patient's world. Mountain milkmaid's working day]. PMID- 2252833 TI - [From the patient's world. Patients as objects--patients as person?]. PMID- 2252834 TI - Pressure sores--a manager's perspective. PMID- 2252835 TI - Temperature taking--getting it right. PMID- 2252836 TI - The Charing Cross approach to venous ulcers. PMID- 2252837 TI - Regulation of haemopoietic cell development by growth factors. PMID- 2252838 TI - Selectivity of protein kinase inhibitors in human intact platelets. AB - The specificity of commonly used protein kinase inhibitors has been evaluated in the intact human platelet. Protein kinase C (PKC) and cyclic AMP-dependent protein kinase (PKA) were activated selectively by treating platelets with phorbol dibutyrate (PDBu) or prostacyclin (PGl2). PKC activity was quantitated by measuring PDBu-specific phosphorylation of a 47,000 molecular weight protein, and PKA activity monitored by measuring prostacyclin-dependent phosphorylation of a 22,000 molecular weight protein. Staurosporine and 1-(5-isoquinolinylsulphonyl)-2 methyl-piperazine (H-7) were found to be non-specific inhibitors in the intact platelet, consistent with their effects on the isolated enzymes. Tamoxifen inhibited PKC activity (IC50 = 80 microM) but increased PKA-dependent protein phosphorylation. These results support the use of human platelets for measuring the specificity of protein kinase inhibitors and indicate that tamoxifen might have value for experimental purposes as a relatively selective PKC inhibitor. PMID- 2252839 TI - Daurisoline derivatives inhibit the ability of calmodulin to stimulate cyclic nucleotide phosphodiesterase activity. AB - Daurisoline alkaloid derivatives were found to be potent calmodulin (CaM) antagonists. The ability of daurisoline derivatives to attenuate the stimulatory effect on calmodulin activated cyclic nucleotides phosphodiesterase (CaM-PDE) was studied. These compounds did not inhibit the basal activity of this enzyme. The hydrophobicity of these compounds was related to their inhibitory potency. It is suggested that such drugs bind directly to calmodulin in a Ca2(+)-dependent fashion, as indicated by their ability to change calmodulin fluorescence. PMID- 2252840 TI - Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells. AB - The effects of tamoxifen (TAM) on cell proliferation and voltage-dependent K+ channels were studied on the mouse neuroblastoma cells NG 108-15. TAM inhibited cell proliferation with an effective dose inducing a half maximum effect (ED50) of 2 microM and was cytotoxic from and beyond 2.5 microM. TAM accelerated the apparent inactivation of the whole cell K+ current with an apparent dissociation constant of 0.46 microM, and shifted the peak K+ conductance-voltage curve towards negative voltages with an apparent dissociation constant of 1.07 microM. The K+ flux at the resting potential, calculated from the time integral of the K+ current recorded during depolarizations, was decreased by TAM. The effect of TAM on the cell proliferation was perfectly correlated with the effect of TAM on the resting K+ flux. The results suggest that cell mitosis is, in some way, controlled by the functioning of K+ channels and that the antitumour action of tamoxifen could be due to its interaction with K+ channels. PMID- 2252841 TI - Racemates versus enantiomers in drug development: dogmatism or pragmatism? PMID- 2252842 TI - Stereoselective disposition of ibuprofen and flurbiprofen in rats. AB - (R)-2-Arylpropionates are often inverted to the pharmacologically active S enantiomers in vivo, although there is significant interspecies variability in inversion. In order to provide a basis for determining the biochemical consequences of this unique process using rats as a model, it was important to establish the pharmacokinetic disposition of the enantiomers of ibuprofen, a drug well inverted in man and flurbiprofen, a drug apparently poorly inverted in man. Rats were dosed i.v. with a single dose of (R)- or (S)-ibuprofen (20 mg/kg), (R,S)-ibuprofen (40 mg/kg), (R)- or (S)-flurbiprofen (10 mg/kg), or (R,S) flurbiprofen (20 mg/kg). Each treatment group consisted of six animals. Serial blood samples were withdrawn over a period of 6 h for ibuprofen and 10 h for flurbiprofen. These drugs were assayed in plasma by a stereospecific HPLC assay. The pharmacokinetics of the ibuprofen and flurbiprofen enantiomers were evaluated using a two-compartment open model with conversion of the R- to S-enantiomers in the central compartment. There was 50 +/- 4% inversion of (R)-ibuprofen, a figure similar to that observed in man and (R)-ibuprofen had a higher clearance (12.6 +/ 1.3 ml/min/kg) than (S)-ibuprofen (7.7 +/- 0.7 ml/min/kg; P less than 0.01). The clearance of (R)-flurbiprofen after racemate (2.3 +/- 0.1 ml/min/kg) was higher than its clearance when administered alone (1.7 +/- 0.2 ml/min/kg; P less than 0.01), indicating a pharmacokinetic interaction between the enantiomers (most probably at plasma protein binding sites). A corresponding difference was not observed for ibuprofen. There was a small amount of inversion of (R)-flurbiprofen as determined by area analysis (4.5 +/- 1.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252843 TI - Enantioselective aliphatic hydroxylations of racemic 1-hydroxy-3 methylcholanthrene by rat liver microsomes. AB - Enantiomeric pairs of 1-hydroxy-3-hydroxymethylcholanthrene (1-OH-3-OHMC), 3 methylcholanthrene (3MC) trans- and cis-1,2-diols, and 1-hydroxy-3 methylcholanthrene (1-OH-3MC) were resolved by HPLC using a covalently bonded (R) N-(3,5-dinitrobenzoyl)phenylglycine chiral stationary phase (Pirkle type 1A) column. The absolute configuration of an enantiomeric 3MC trans-1,2-diol was established by the exciton chirality CD method following conversion to a bis-p N,N-dimethylaminobenzoate. Incubation of an enantiomeric 1-OH-3MC with rat liver microsomes resulted in the formation of enantiomeric 3MC trans- and cis-1,2 diols; the absolute configurations of the enantiomeric 1-OH-3MC and 3MC cis-1,2 diol were established on the basis of the absolute configuration of an enantiomeric 3MC trans-1,2-diol. Absolute configurations of enantiomeric 1-OH-3 OHMC were determined by comparing their CD spectra with those of enantiomeric 1 OH-3MC. The relative amount of three aliphatic hydroxylation products formed by rat liver microsomal metabolism of racemic 1-OH-3MC was 1-OH-3-OHMC greater than 3MC cis-1,2-diol greater than 3MC trans-1,2-diol. Enzymatic hydroxylation at C2 of racemic 1-OH-3MC was enantioselective toward the 1S-enantiomer over the 1R enantiomer (approximately 3/1); hydroxylation at the C3-methyl group was enantioselective toward the 1R-enantiomer over the 1S-enantiomer (approximately 58/42). Rat liver microsomal C2-hydroxylation of racemic 1-OH-3MC resulted in a 3MC trans-1,2-diol with a (1S,2S)/(1R,2R) ratio of 63/37 and a 3MC cis-1,2-diol with a (1S,2R)/(1R,2S) ratio of 12/88, respectively. PMID- 2252844 TI - Enantioselective hydrolysis of oxazepam 3-acetate by esterases in human and rat liver microsomes and rat brain S9 fraction. AB - Rates of hydrolysis of racemic and enantiomeric oxazepam 3-acetates (OXA) by esterases in human and rat liver microsomes and rat brain S9 fraction were compared. When rac-OXA was the substrate, esterases in human and rat liver microsomes were highly enantioselective toward (R)-OXA. In contrast, esterases in rat brain S9 fraction were highly enantioselective toward (S)-OXA. Hydrolysis rates of rac-OXA were highly dependent on the amount of esterases used. At 0.05 mg protein equivalent of esterases and 150 nmol of rac-OXA per ml of incubation mixture, the (R)-OXA was hydrolyzed 3.6-fold and 18.5-fold faster than (S)-OXA by rat and human liver microsomes, respectively. The specific activities (nmol of OXA hydrolyzed/mg microsomal protein/min) of liver microsomes in the hydrolysis of enantiomerically pure (R)-OXA were approximately 120 (rat) and 1,980 (human), and in the hydrolysis of enantiomerically pure (S)-OXA were 4 (rat) and 7 (human), respectively. In the incubation of rac-OXA with rat brain S9 fraction, (S)-OXA was hydrolyzed approximately 6-fold faster than (R)-OXA. Results also indicated an enantiomeric interaction in the hydrolysis of rac-OXA by esterases in rat and human liver microsomes; the presence of (R)-OXA stimulated the hydrolysis of (S)-OXA, whereas the presence of (S)-OXA inhibited the hydrolysis of (R)-OXA. In rat brain S9 fraction, the presence of (R)-OXA inhibited the hydrolysis of (S)-OXA, whereas the presence of (S)-OXA appeared to have stimulated the hydrolysis of (R)-OXA. PMID- 2252845 TI - Stereochemical features of 1,4-benzodiazepin-2-ones bound to human serum albumin: difference CD and UV studies. AB - The stereochemistry of an achiral (Diazepam) and two chiral (3-methyl and 3 succinyloxy substituted) 1,4-benzodiazepin-2-ones interacting with human serum albumin (HSA) has been investigated by making use of difference absorption (UV) and circular dichroism (CD) spectroscopies. Evidence is obtained for a higher affinity with HSA for one of the two possible conformations of the seven-membered benzodiazepine ring. The red shift revealed by the absorption difference spectrum between the free and the bound drug accounts for the CD difference spectra observed. PMID- 2252846 TI - Direct resolution of some phenylglycines by liquid chromatography on a chiral crown ether phase. AB - The optical resolution of a series of 12 amino acids of the phenylglycine family was studied using a chiral crown ether column. The effects of pH, temperature, and mobile phase additive were investigated. In three examples it was confirmed that the R enantiomer eluted prior to the S enantiomer. Most phenylglycines were resolved with large separation factors; those with two functional groups substituents on opposing sides of the phenyl ring, however, were not well separated. PMID- 2252847 TI - [Consequences of resecting the ileocecal union]. AB - 22 patients, divided in 2 groups, are studied under-going intestinal resection as consequence of different pathological entities. Group I of 13 patients who had the ileocecal union resected. Group II is made up of 9 patients who had small fragments of the small intestine enucleated. All the patients have, among other things, various anthropometrical, hematological and biochemical parameters, and their Ca/P metabolism analyzed, as well as the elimination of urinary nitrogen in its different forms. The patients who underwent resection of the ileocecal union present anthropometrical alterations, which can be consequence of a state of chronic malnutrition. The differences found in the alkaline phosphatase and in the elimination of amino acids in the urine can be a sign of a bacterial contamination of the small intestine by fecal flora or a sign of less availability of energetic contribution. PMID- 2252848 TI - [Is it necessary to remove polycystic kidneys?]. AB - The Multicystic Dysplastic Kidney is the most frequent renal congenital anomaly and the second most common cause of an abdominal mass in the newborn. Traditionally, since this pathological entity was described as such by Spene in 1955, early resection has been deemed its best treatment. In the last decade, a conservative approach has been advocated by some authors, except for the patients presenting with concomitant abdominal pain or infection. In our hospital, relying on the support afforded by the echographic assessment of these patients, we have proposed an expectant behaviour in the management of this entity. So far, we have had the opportunity to follow the course of the disease in 15 patients with the diagnosis of Multicystic Dysplastic Kidney, with the result that in no one of them the size of the cystic mass increased, but instead the mass disappeared completely in one case, diminished greatly in three cases, had a moderate decrease in size in eight cases and in just three patients it has not varied in size. No patient has complained of abdominal pain or has become infected. In the face of such findings, we believe that early resection of the multicystic kidney is not warranted if no complications develop. PMID- 2252849 TI - [Acidic stimulation of esophageal peristalsis: its prognostic value in reflux]. AB - Gastroesophageal Reflux (GER) in children manifests itself by several clinical pictures. Its diagnosis is difficult and so are surgical indications. The search for prognostic parameters able to predict the need for surgery are therefore warranted. We have demonstrated in previous studies in children with GER a decrease in propulsive peristalsis and an increase in non-propulsive activity. We have also reported that patients able to respond to medical treatment correct their motor trouble when acid is instilled into the esophagus, whereas those unable to respond to it do not. Aiming at clarifying the prognostic value of this acid challenge test we have thus measured Esophageal Motor Efficiency (EME) (prop. waves/h multiplied by mean pressure) in basal conditions and after acid challenge in 52 children divided into two groups according to their response to medical treatment during periods exceeding 6 months. EME in basal conditions did not allow differentiation between both groups, but EME after acid challenge did so. Optimum threshold value was 565, sensitivity 0.76, specificity 0.75, positive predictive value 87%, and negative predictive value 60%. This test seems to have some prognostic value in pediatric GER. PMID- 2252850 TI - [Our experience in the treatment of cervico-facial adenitis caused by non tuberculous mycobacteria (atypical mycobacteria)]. AB - The authors believe that the greater part of chronic cervicofacial adenitis actually observed in our hospitals, are not caused by M. tuberculosis or M. bovis but by scrofulaceum mycobacterium, M. avium, M. fortuitum and M. Kansasii, and above all, by the first two of these. They present their experience with 16 cases of cervico-facial adenitis due to atypical mycobacterium (CAAM) treated in our centre during the last years, in which period no case of cervical tuberculosis (CT) was observed. It is important to establish an early differential diagnosis between both etiologies, seeing as treatment is different. Whilst tuberculostatics can solve the phymic infection, surgical extirpation is the only solution for CAAM. The diagnosis of these types of infection is achieved by means of a very characteristic clinical procedure and by cutaneous tests specific for each bacteria. Faced with the clinical suspicion, the total extirpation should be effected of the adenopathic block affected. The exact diagnosis can only be made by the culture of the operatory mass. PMID- 2252851 TI - [Follow-up and evolution of 10 cases operated on for total colonic aganglionosis]. AB - One hundred sixty-one cases of HIRSCHSPRUNG's disease have been operated on by us between 1966 and 1988. Of these, 19 were total colonic aganglionosis. Of eleven that underwent surgery before 1982, five are still alive. The eight that were operated on after 1982 have a good evolution. This report is a retrospective study of the clinical evolution in ten of the thirteen survivors. The ages are comprised between 21 and 2 1/2 years. We have reviewed their general condition, weight, height, tolerance to oral intake, stool frequency, general laboratory determinations, circulating iron, transferrin, transferrin saturation, absorption of vitamin B12 and folic acid, hydrogen test and stool examination. Except for one case, the others are in a perfect nutritional and growth condition. DUHAMEL's technique was employed in eight cases and REHBEIN's technique, in two. Given our good results, we think that LESTER-MARTIN's technique is unnecessary, except for that cases with extensive small bowel involvement due to the serious problems of absorption that this represents. PMID- 2252852 TI - [Surgical treatment of differentiated carcinoma of the thyroid. Retrospective study]. AB - This is a review of the surgical treatment in six patients with papillary carcinoma of the thyroid. The mean age at the time of diagnosis was eight years (range four-twelve years). Clinical presentation was: all patients had a palpable thyroid tumor, palpable lymph nodes in four and one with lung metastases. The initial surgical treatment was lobectomy and modified regional lymph nodes resection. Four patients underwent a second operation for multifocal disease, palpable lymph node or thyroid tumor. The interval from initial surgical management to the detection of recurrence ranging from one month to four years. In three patients the remaining thyroid gland was removed. Radioiodine, external irradiation and chemotherapy were given during the postoperative. The median follow-up was eight years (range one-fifteen years). All patients are alive with thyroid hormone therapy by hypothyroidism. There were no hypoparathyroidism or injuries to the recurrent laryngeal nerve. The results of this study suggest that the surgical approach in papillary carcinoma of the thyroid is total thyroidectomy because reoperation were performed in four patients. PMID- 2252853 TI - [Results of biofeedback on incontinence caused by anorectal atresia]. AB - Eight patients with anorectal incontinence because of anorectal atresia, aged between seven and seventeen years, following surgical treatment with Romualdi Soave procedure in seven cases and with PSARP in one case, have received biofeedback training to improve their continence. Clinical evaluation has been performed with a new numeric punctuation method that allows a quantitative and precise appraisal of incontinence (Incontinence Punctuation: IP). From a clinical point of view, biofeedback training has increased 4.16 points IP in patients in whom the method has been effective. It has prolonged the mean duration of voluntary contraction in 5.9 sec. and elevated in 13.6 mm. Hg. the maximal pressure contraction. In two patients, clinical evolution and manometry measurements indicated surgical treatment and PSARP was performed, improving IP in 5.5 points. We considered biofeedback training, when indicated, an adequate and innocuous technique to achieve an important clinical continence improvement in these patients. PMID- 2252854 TI - [Meconial peritonitis: conclusions based on 53 cases]. AB - The study of 53 patients with neonatal meconium peritonitis (MP) over a twenty two year-period, the largest surgically-treated series at a single centre, is presented. Three different types of MP were established: Generalized, Localized and Cystic. Prognosis and surgical techniques to be used were determined by each MP type. The following survival rates achieved: for Generalized MP, 70% with "one stage" and 89% with "two stage"; for Localized MP, 80% with "one stage" and 100% with "two stage" and for Cystic MP, 57% with "two stage". The overall survival rate was 77%, rising to 85% in the last fifteen years, probably due to the advent of parenteral nutrition and advances in neonatal intensive care. PMID- 2252856 TI - [Emergencies of the left colon: what tactics?]. PMID- 2252855 TI - [Cervical thymic cysts in children]. AB - Two cases of Cervical Thymic Cysts are communicated, a seven old year boy and a four year old girl, operated on the last three years. Both children suffered for one month an asymptomatic cervical mass. Preoperative studies included: Roentgenogram study, Ultrasound, CT scan and 131 I scan. The diagnosis was established by excision and Histological study. The clinical, anatomical and histological characteristics, were similar to the few published cases (79 cases). PMID- 2252857 TI - [Carotid thromboendarterectomy in old age]. AB - Data obtained in 323 carotid bifurcation endarterectomies and in 77 patients affected by extracranial internal carotid artery stenosis not operated, have been analyzed in relation to patients' age: Group 1 less than or equal to 69 years old (268 cases operated on and 59 not operated), and Group 2 greater than or equal to 70 years old (55 cases operated on and 18 not operated). Among the operated patients, the most important anaesthetic risk factors, the type of neurological symptoms, and the diameter of the lesion did not turn out significantly different between the two age groups, except for the patients operated on because of stenoses less than or equal to 50% of carotid lumen reduction (42 cases in Group 1 and 1 case in Group 2, p less than 0.001). The overall operative mortality rate was 1.8% (6/323 carotid endarterectomies): 1.5% in Group 1 (4/268 cases, 2 due to stroke and 2 to heart disease), and 3.6% in Group 2 (2/55 cases, both due to stroke) (N.S.). The overall neurological morbidity was 0.6%, owing to 2 strokes both found in Group 2 (3.6% of patients greater than or equal to 70 years). Therefore, the overall incidence of fatal and non fatal stroke was 1.8% (6/323 carotid endarterectomies): 0.7% (2 cases) in Group 1, and 7.3% (4 cases) in Group 2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252858 TI - [Anatomical and surgical considerations on the internal spermatic venous system]. AB - The surgical anatomy of the spermatic venous system is described. Thereafter an experimental evaluation performed on cadavers by the vascular mould technique using plastic materials is reported. The resulting data point out the complex variability of the spermatic venous circulation, stressing the value of preoperative phlebography in the surgical approach to varicocele. PMID- 2252859 TI - [Surgery in aged patients: a study on 476 surgical cases]. AB - The Authors report their experience from 1984 to 1989 with surgery in the elderly. Patients aged 75 years were considered as geriatric and entered the study. Mortality and morbidity rates were analysed in 476 cases operated. Pre existent diseases were related to postoperative complications. The Authors conclude underlining the feasibility of geriatric surgery as well as the acceptable risk rate. PMID- 2252860 TI - [Immediate complications in thyroid surgery]. AB - The Authors report the results of a series of 502 thyroid operations (bilateral in 322 cases [64%] and unilateral in 180 cases [36%]), with the aim to evaluate the incidence of early complications and to establish when they were more likely to occur. Preoperative diagnosis was based on scintigraphic scan recently combined to ultrasonography with fine needle biopsy. In all patients a pre and postoperative control of vocal cords motility was performed. Intraoperative identification of recurrent laryngeal nerve was the rule. Complications include a single case of mortality due to cerebral haemorrhage, 2 cases of monolateral recurrent laryngeal nerve paralysis, 4 cases of transient dysphonia, 8 cases of temporary hypoparathyroidism, 5 cases of postoperative bleeding. In three patients a temporary tracheostomy was needed. Thyrotoxic storm did not occur and wound infections were negligible. The various thyroid diseases and their different biological behavior are responsible of the risk factors, local and general ones, which the surgeon must recognize. Diagnostic accuracy, meticulous surgical technique and the best treatment at the first approach are the main factors to prevent complications in thyroid surgery. PMID- 2252861 TI - [Clinico-statistical findings in Fournier's gangrene]. AB - Pathophysiological mechanisms of Fournier's gangrene are reported. Variety and progression of clinical manifestations are stressed as well. The importance of an accurate therapeutic protocol in the treatment of this peculiar and serious disease is therefore underlined. PMID- 2252863 TI - Acquired immunodeficiency syndrome (AIDS). Surveillance update to 30 June 1990 in the WHO European Region. PMID- 2252862 TI - [Percutaneous drainage of liver abscesses]. AB - Three patients with hepatic abscess were treated by percutaneous drainage ultrasonographically or tomographically guided. The treatment was effective in two out of three patients. The low morbidity and the high success rate obtained suggest that this therapeutic modality should be used before considering any surgical approach. PMID- 2252864 TI - HIV antibody screening of blood donations 1987-1989. PMID- 2252865 TI - Chronic disease surveys. Evaluation of hypertension screening in a Swiss community using the cluster survey methodology of the EPI. PMID- 2252866 TI - Measles. Measles outbreak, Chicago, 1989. PMID- 2252867 TI - The effect of established and gestational diabetes on pregnancy outcome. AB - OBJECTIVE: To study the prevalence and type of glucose intolerance in pregnancy and the effect of different types on perinatal mortality and fetal size. DESIGN: A prospective case-control study with data collected by patient interview and examination of all available records during a 16-months period between 1984 and 1986. SETTING: A large maternity hospital in Kuwait where diabetes in pregnancy is common. SUBJECTS: The cases were a consecutive sample of 731 women, delivered during the study period, recorded in the labour ward register as being diabetic or having abnormal glucose tolerance, the control group was formed from the next woman in the register (provided she was not known to be diabetic). MAIN OUTCOME MEASURES: Type of diabetes followed the WHO classification, with subdivision depending on level of fasting plasma glucose. Type of perinatal death was examined in detail and birthweight centile calculated. RESULTS: Of the 731 cases, 22% were established diabetics, most were treated with oral hypoglycaemic drugs before pregnancy and insulin during pregnancy. Of those discovered during pregnancy, 43% were classified as gestational diabetes and the remainder as impaired glucose tolerance. Overall, 50% of cases were treated with insulin. Established diabetics had a perinatal mortality rate nearly four times greater than non diabetics (RR, 3.7, 95% CI 2.6 to 6.4) and for gestational diabetics RR was 2.0 95% CI 1.2 to 3.7). Unexplained deaths were particularly common, both in established diabetics (RR, 18.4, 95% CI 3.9 to 85.7) and in gestational diabetics (RR, 13.4, 95% (CI 2.9 to 61.6). Cases with impaired glucose tolerance had no stillbirths and had a lower perinatal loss than the controls, though this was not statistically significant. Heavier babies were seen in all case groups compared with controls, though the impaired glucose tolerance group had lower birthweights than the other two case groups. CONCLUSIONS: Type 2 diabetes was found to be common, most cases being diagnosed in pregnancy. Under the conditions found in Kuwait, diabetes, in the sense of a raised fasting glucose, is accompanied by a high rate of perinatal loss from unexplained stillbirth. This applies whether the condition was present before pregnancy or was discovered during pregnancy. Fetal macrosomia was also common in both situations. Impaired glucose tolerance, where fasting levels remain normal, does not appear to increase fetal loss, but may be associated with fetal macrosomia. As these women age they are likely to develop overt diabetes in the non-pregnant state, and subsequently to develop serious complications of this disease. Improving glycaemic control, both during preg PMID- 2252868 TI - The use of rectus abdominis myocutaneous flaps following excision of vulvar cancer. AB - Rectus abdominis myocutaneous flaps have been used in 16 women following radical excision of extensive vulvar cancer. In two women the procedure was part of the primary surgery, in 11 for recurrence of vulvar cancer and in three for symptomatic palliation. Fifteen (94%) of the grafts took with primary healing. Thirteen of the 16 patients are alive 6-60 months (median 29 months) after surgery and the three who died benefited from symptomatic palliation. Simultaneous vulvar reconstruction allows good cosmetic rehabilitation and is an important part of the armamentarium for the management of patients with advanced primary or recurrent vulvar carcinoma. This technique offers excellent surgical clearance of massive offensive and painful vulvar tumors. PMID- 2252869 TI - Regional differences in vascular responses in the human uterus. AB - Tissue specimens from the fundus, isthmus and distal cervix were obtained from 14 women at hysterectomy at various phases of the menstrual cycle. Ring preparations of small intramyometrial and intracervical arteries were dissected and mounted in organ baths; isometric tension was recorded and responses to contractile agents were studied. The amplitude of responses to K+ (124 mmol/l) of the vessel preparations ranked fundus greater than or equal to isthmus greater than cervix. While similar pD2 values for noradrenaline (NA) were found, the Emax values ranked cervix greater than or equal to isthmus greater than or equal to fundus (cervix greater than fundus). The pD2 values for arginine-vasopressin (AVP) showed minor differences, while the Emax values for this peptide ranked fundus greater than or equal to isthmus greater than or equal to cervix (fundus greater than cervix). Arteries from the fundus and isthmus displayed weak, inconsistent contractile responses to prostaglandin F2 alpha, but more pronounced contractions were induced by this prostanoid in arterial preparations from the distal cervix. The results suggest regional differences in vascular mechanical responses to endogenous vasoactive agents in the human uterus. PMID- 2252870 TI - Transvaginal ultrasound for diagnosis of uterine malformations. AB - Uterine malformations were detected in 8 of 300 patients (3%) referred for transvaginal ultrasound scan (TVS) for different indications. Six of them had a partially septate uterus and two had a uterus didelphys. As uterine malformations can be associated with both sterility and reproductive failure, we suggest that the study of uterine morphology and structure could be a part of routine TVS examination. PMID- 2252871 TI - Hypercalcaemia in pregnancy in a renal transplant recipient with secondary hyperparathyroidism. Case report. PMID- 2252872 TI - Uterine rupture in midtrimester abortion. A complication of gemeprost vaginal pessaries and oxytocin. Case report. PMID- 2252873 TI - Has in-vitro fertilization made salpingostomy obsolete? PMID- 2252874 TI - Effective care in pregnancy and childbirth. PMID- 2252875 TI - Andrology: a new sub-specialty. PMID- 2252876 TI - Non-surgical treatment of ectopic pregnancy. PMID- 2252877 TI - A morphological and immunological study of human placental bed biopsies in miscarriage. AB - Placental bed biopsies were examined in three groups of pregnant women for maternal vascular response to placentation as well as for the presence of cells associated with local immunosuppression activity. In the group of women undergoing legal abortion, the histological appearance of trophoblastic invasion was normal in all but one, and the proportion of immunosuppressor cells was also normal. In the missed miscarriage group the histological appearances were abnormal except in one patient. In women with a history of recurrent miscarriage who had miscarried after immunization, placentation was normal in some and defective in others. Immunosuppressor cells appeared to be diminished in number, although there was no correlation between the cytotoxic status of their sera and their pregnancy outcome. PMID- 2252878 TI - Embryonic heart activity: appearance and development in early human pregnancy. AB - The appearance and development of embryonic cardiac activity was studied in early human pregnancies established by in-vitro fertilization (IVF) using transvaginal sonography. Embryonic cardiac activity could be detected as early as 25 days after follicle aspiration. The range in appearance of embryonic cardiac activity in normal continuing pregnancies was 5 days. There was no correlation with maternal age, day of embryo transfer, or cell stage at embryo transfer. As the difference in appearance of embryonic cardiac activity was associated with a difference in crown-rump length whilst the subsequent growth curve was normal we ascribe these findings to different duration of the implantation stage. The later cardiac activity was detected the greater the risk of miscarriage. Reference curves were created relating embryonic heart rate to the number of days after follicle aspiration, the number of days that cardiac activity is present and the crown-rump length. In pregnancies ending in miscarriage heart rate patterns fell away from the reference curve. Embryonic factors seem to play an essential role in these observations. PMID- 2252879 TI - Large loop excision of the transformation zone (LLETZ) compared to carbon dioxide laser in the treatment of CIN: a superior mode of treatment. AB - A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or III were allocated by hospital number to receive out patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone (LLETZ). All patients received local anaesthesia. The women in the LLETZ group experienced less post operative haemorrhage, less discomfort, operative time was greatly reduced, and histological material was available for confirmation of the diagnosis. There was no significant difference in recurrence of CIN after treatment between the two groups. At 6 month follow up, recurrence rates of 8.2% (CIN II) and 7.5% (CIN III) were observed in the laser-group and 5% (CIN II) and 5.3% (CIN III) in the LLETZ group. Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon, but laser treatment is preferable in patients with widespread vaginal involvement. PMID- 2252880 TI - Total perinatal wastage. A clarification of priorities. AB - The pregnancy outcome of 16,971 women carrying 17,352 living fetuses after 16 weeks gestation was studied. As well as recording perinatal deaths, all losses before 28 weeks and up to one year after delivery were recorded to give a total perinatal wastage rate of 21.6 per 1000 fetuses alive at 16 weeks compared with a perinatal mortality rate (stillbirths plus early neonatal deaths) of 7.8 per 1000 births. All deaths were then classified according to pathological sub-groups. The concept of auditing perinatal care using perinatal mortality was then compared with that using total perinatal wastage. PMID- 2252881 TI - Secondary structure of the mammalian 70-kilodalton heat shock cognate protein analyzed by circular dichroism spectroscopy and secondary structure prediction. AB - Heat shock proteins are rapidly synthesized when cells are exposed to stressful agents that cause protein damage. The 70-kDa heat shock induced proteins and their closely related constitutively expressed cognate proteins bind to unfolded and aberrant polypeptides and to hydrophilic peptides. The structural features of the 70-kDa heat shock proteins that confer the ability to associate with diverse polypeptides are unknown. In this study, we have used circular dichroism (CD) spectroscopy and secondary structure prediction to analyze the secondary structure of the mammalian 70-kDa heat shock cognate protein (hsc 70). The far ultraviolet CD spectrum of hsc 70 indicates a large fraction of alpha-helix in the protein and resembles the spectra one obtains from proteins of the alpha/beta structural class. Analysis of the CD spectra with deconvolution methods yielded estimates of secondary structure content. The results indicate about 40% alpha helix and 20% aperiodic structure within hsc 70 and between 16-41% beta-sheet and 21-0% beta-turn. The Garnier-Osguthorpe-Robson method of secondary structure prediction was applied to the rat hsc 70 amino acid sequence. The predicted estimates of alpha-helix and aperiodic structure closely matched the values derived from the CD analysis, whereas the predicted estimates of beta-sheet and beta-turn were midway between the CD-derived values. Present evidence suggests that the polypeptide ligand binding domain of the 70-kDa heat shock protein resides within the C-terminal 160 amino acids [Milarski, K. L., & Morimoto, R. I. (1989) J. Cell Biol. 109, 1947-1962].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252882 TI - Folding of the reduced form of the thioredoxin from bacteriophage T4. AB - The folding pattern for bacteriophage T4 thioredoxin is similar to that of the oxidized form [Borden, K. L. B., & Richards, F. M. (1990) Biochemistry 29, 3071 3077]. Equilibrium and kinetic studies were carried out by fluorescence and circular dichroism techniques. The same box model proposed for the oxidized form, with four identifiable states, can accommodate most of the data: N----Uc----Ut--- It----N, where N is the native state, Uc is the unfolded species with Pro 66 in the cis form, Ut is the unfolded species with Pro 66 in the trans form, and It is a trans-Pro 66 intermediate with a volume comparable to that of N. However, the relative importance of the different components is shifted between the oxidized and reduced proteins. In spite of the small size of the disulfide loop, the Cys 14-Cys 17 bond appears to be important in stabilizing It. The tertiary structure as monitored by near-UV CD and fluorescence indicates that the reduced form is significantly less stable than its oxidized counterpart; however, the two secondary structures, as seen by far-UV CD, are very similar. The intermediate It behaves as though it is cold denaturated at 4 degrees C. PMID- 2252883 TI - Nonnative isomers of proline-93 and -114 predominate in heat-unfolded ribonuclease A. AB - The peptide bonds preceding both Pro-93 and Pro-114, which are in the cis conformation in native RNase A, are predominantly in the trans conformation in the heat-unfolded protein. The percentages are estimated to be 60% and 63%, respectively, with a standard deviation of +/- 7% in each quantity. These ratios are close to those found for corresponding sequences in X-Pro-Y peptides. The concentration of the trans proline species was determined from the integrated intensities of resonance peaks of the C alpha H protons of Tyr-92 and Asn-113, which are well resolved in the 1D proton NMR spectrum of heat-unfolded RNase A. The assignments of the resonances were deduced from 2D NOESY and DQF-COSY spectra of unfolded RNase A in D2O. Furthermore, the C alpha H protons of both Tyr-92 and Asn-113 had an intense NOE cross-peak with the C delta H and C delta' H of the respective following prolines. For both Pro-93 and Pro-114, these NOE cross-peaks would arise only if the X-Pro peptide bond were in the trans conformation. It is generally believed that the rate of refolding of RNase A is considerably reduced by nonnative proline isomers, such as trans Pro-93. Two models for folding RNase A, that are consistent with these new results and the work of previous investigators, are presented here. PMID- 2252884 TI - Stability and reconstitution of the soluble variant surface glycoprotein (sVSG) from Trypanosoma brucei. AB - Soluble variant surface glycoprotein (sVSG) is the form of the coat protein of Trypanosoma brucei released by cleavage of its lipid anchor. As shown by ultracentrifugal analysis, the protein of the variant clone MITat 1.2 is a stable dimer of (117 +/- 6)-kDa molecular mass. Its quaternary structure remains unaltered in the concentration range from 0.01 to approximately 50 mg/mL. Further extrapolation to the in situ concentration on the cell surface points to no significant protein association beyond the dimer, because after correction for solution viscosity sedimentation velocity is independent of the protein concentration. The sedimentation constant, s20,w = 5.1 X 10(-13) s, together with the particle weight confirms the high anisotropy of the dimer. Circular dichroism and fluorescence spectra show the typical properties of an alpha-helical protein (51% alpha-helix) with fluorophores buried in the hydrophobic interior of the protein. Denaturation at extremes of pH leads to the monomer still maintaining a relatively compact structure. Increased concentrations of urea and guanidine hydrochloride cause randomization with cooperative transitions at 1.7 and 0.7 M, respectively. The yield of reconstitution of the denatured protein reaches 87% under optimum conditions. The final product is indistinguishable from the native protein in its spectral, hydrodynamic, and immunochemical properties. Immunological analysis included polyclonal antibodies as well as monoclonal antibodies raised against epitopes in the surface of the complete trypanosome, as well as cryptic epitopes exposed only on sVSG in solution. The kinetics of reconstitution involve sequential uni-bimolecular processes, corresponding to consecutive folding and subunit association. About 38% of the fluorescence of the native protein is recovered within the mixing time (secondary structure formation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252885 TI - Extraction of the energetics of selected types of motion from molecular dynamics trajectories by filtering. AB - A novel method for analyzing molecular dynamics trajectories has been developed which enables the study of selected motions and the corresponding energetics. In particular, it is possible to filter out the high-frequency motions and focus on the structural and energetic features of low-frequency collective motions. The trajectories of the properties of interest are Fourier transformed to the frequency domain, a filtering function is applied, and then an inverse transformation back to the time domain yields the filtered trajectory. The method is demonstrated for harmonic fluctuations and conformational transitions of acetamide and N-acetylalanine N-methylamide, as models for peptides and proteins. PMID- 2252886 TI - The role of charge and hydrophobicity in peptide-lipid interaction: a comparative study based on tryptophan fluorescence measurements combined with the use of aqueous and hydrophobic quenchers. AB - The interaction of interrelated model peptides with model membranes has been studied by techniques based on tryptophan fluorescence. The peptides used are derivatives of the sequence H-Ala-Met-Leu-Trp-Ala-OH, which was designed for this purpose. Several modifications yielded a set of 13 penta- and hexapeptides varying in net charge, hydrophobicity, charge distribution, and the intramolecular position of the tryptophan residue with respect to the charge(s). The affinity of these peptides for small unilamellar vesicles (SUV) consisting of zwitterionic egg phosphatidylcholine (eggPC) and negatively charged beef heart cardiolipin (bhCL) has been investigated in a comparative way. The criteria for affinity comprise (1) intrinsic fluorescence changes upon titration of the peptides with the lipid vesicles, (2) reduced accessibility of the peptides to aqueous quenchers of tryptophan fluorescence (I- and acrylamide) in the presence of lipid, and (3) exposure to membrane-incorporated fluorescence quenchers, brominated phosphatidylcholines (BrPC). Application of BrPC brominated at different positions along the acyl chains provided information on the membrane topology of the peptides. With respect to the extent of affinity for zwitterionic membranes, the overall hydrophobicity of the peptides is the main determinant. A comparison of the affinity for PC of equally hydrophobic peptides carrying either a single positive or negative charge reveals preferential interaction of the cationic peptide. Both hydrophobic and electrostatic interactions determine the affinity of positively charged mono- and divalent peptides for CL vesicles. The distribution of the charged moieties in divalent positively charged peptides, either both at one end of the molecule or one at each end, has little influence on the affinity of these peptides for CL but does affect the extent of exposure to BrPC. Upon decreasing the surface charge density of the vesicles by diluting CL with increasing amounts of PC, both types of peptides show different behavior. The position of the tryptophan relative to the charged moiety in the peptide molecule is shown to affect the fluorescent properties upon interaction with vesicles. Concerning the membrane topology, all peptides adopt a localization near the membrane surface, with the neutral peptides inserting slightly deeper into the bilayer than the charged peptides. The results allow a comparative analysis of the factors determining the extents and modes of lipid-model peptide interaction; in addition, the validity of the methods applied is discussed. PMID- 2252887 TI - Structure and chemical modifications of neurotoxin from Naja nigricollis studied by Raman spectroscopy. AB - Raman spectroscopy was used to determine structural features of the native toxin alpha from Naja nigricollis, which contains only one Trp and one Tyr, and of chemically modified toxins having chromophores added to these two conserved aromatic amino acids. The percentages of secondary structure were determined by using amide I polypeptidic vibration analysis and are in agreement with X-ray structure [Low et al. (1976) Proc. Natl. Acad Sci. U.S.A. 73, 2991-2994] as well as with the geometry of the disulfide bridges estimated by using the v(S-S) vibrations. In the native toxin alpha, the single invariant tyrosine 25 appears to be buried in the structure and involved in a strong hydrogen bond. We have chemically modified these two invariant aromatic side chains by addition of chromophores. The presence of a (nitrophenyl)sulfenyl (NPS) chromophore bound to the Trp does not perturb the secondary structure of the toxin as shown by the analysis of the polypeptidic amide I vibrations; however, the environment of this Trp and the geometry of a disulfide bridge seem to be modified. The secondary structure is not affected by the presence of the NPS chromophore; therefore, the decrease in binding affinity observed after modification of Trp-29 by the reagent NPS-Cl [Faure et al. (1983) Biochemistry 22, 2068-2076] is due to an alteration of the environment of this aromatic amino acid and/or a steric hindrance and not to an overall modification of the toxin structure. The binding assays of [nitrotyrosyl]toxin show that after nitration the affinity toward the monoclonal antibody M alpha 1 is unchanged and that the affinity toward the cholinergic receptor (AcChR) from Torpedo marmorata remains high. We concluded that the structure of toxin alpha after adding the NO2 chromophore to Tyr-25 is the same as it is in native toxin. PMID- 2252888 TI - Subunit location and sequences of the cysteinyl peptides of pig heart NAD dependent isocitrate dehydrogenase. AB - Pig heart NAD-dependent isocitrate dehydrogenase has a subunit structure consisting of alpha 2 beta gamma, with the alpha subunit exhibiting a molecular weight of 39,000 and the beta and gamma each having molecular weights of 41,000. The amino-terminal sequences (33-35 residues) and the cysteinyl peptide sequences have now been determined by using subunits separated by chromatofocusing or isoelectric focusing and electroblotting. Displacement of the N-terminal sequence of the alpha subunit by 11-12 amino acids relative to that of the larger beta and gamma subunits reveals a 17 amino acid region of great similarity in which 10 residues are identical in all three subunits. The complete enzyme has 6.0 free SH groups per average subunit of 40,000 daltons, but yields 15 distinguishable cysteines in isolated tryptic peptides. Six distinct cysteines in sequenced peptides have been located in the alpha subunit. The beta and gamma subunits contain seven and five cysteines, respectively, with tryptic peptides containing three cysteines being common to the beta and gamma subunits. The three subunits appear to be closely related, but beta and gamma are more similar to each other than either is to the alpha subunit. The NAD-specific isocitrate dehydrogenase from pig heart has been shown to have 2 binding sites/enzyme tetramer for isocitrate, manganous ion, NAD+, and the allosteric activator ADP [Colman, R. F. (1983) Pept. Protein Rev. 1, 41-69]. It is proposed that the catalytically active tetrameric enzyme is organized as a dimer of dimers in which the alpha beta and alpha gamma dimers are nonidentical but functionally similar. PMID- 2252889 TI - Reconstitution of transferrin receptor in mixed lipid vesicles. An example of the role of elastic and electrostatic forces for protein/lipid assembly. AB - We studied the interaction of transferrin receptors (of cell line Molt-4) with mixed model membranes as a function of lipid chain length (phospholipids with C14:0 and C18:1 hydrocarbon chains) and of the surface charge of the membrane using mixtures of C14:0 lecithin (DMPC) with C14:0 phosphatidylglycerol (DMPG) and C14:0 phosphatidylserine (DMPS). Spontaneous self-assembly of receptors and lipids was achieved by freeze-thaw cycles of a codispersion of mixed vesicles and receptors in buffer and subsequent separation of receptor-loaded and receptor free vesicles by density gradient centrifugation. Information on specific lipid/protein interaction mechanisms was obtained by evaluation of protein induced shifts of phase boundaries of lipid mixtures by calorimetry and by FTIR spectroscopy of partially deuterated lipid mixtures. The important role (1) of minimizing the elastic forces caused by the mismatch of the lengths of hydrophobic cores of the protein (lp) and the bilayer (lL) and (2) of the electrostatic coupling of protein head groups with the charged membrane/water interface for the lipid/protein self-assembly is established. The electrostatic interaction energy per receptor is about 10(3) kBT (by coupling to about 1000 charged lipids) which is sufficient to overcompensate the elastic energy associated with a mismatch of lp - lL approximately 1.0 nm. The maximum receptor concentration incorporated was measured as a function of membrane surface charge and lipid chain length. The maximum receptor molar fraction varied from xpmax = 5 x 10(-5) for DMPC to xpmax = 4 x 10(-4) for 1:1 DMPC/DMPG; moreover xpmax is higher for DMPS than for DMPG as charged component. For the long-chain lipids, xpmax is higher for a 9:1 DEPE/DEPC mixture [(4.2-9) x 10(-4)] than for pure DEPC (ca. 3.5 x 10(-4)). By decomposition of reconstituted receptors with proteases, we demonstrated the homogeneous orientation of the receptor with its extracellular head group pointing to the convex side of the vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252890 TI - Thermodynamics of mixing of phosphatidylserine/phosphatidylcholine from measurements of high-affinity calcium binding. AB - A simple model system is described that allows measurement of equilibrium Ca2+ binding to multilamellar vesicle mixtures of palmitoyloleoylphosphatidylserine (P,O-PS) and dimyristoleoylphosphatidylcholine (MO,MO-PC). The constraint of the chemical equilibrium among aqueous Ca2+, hydrated P,O-PS/MO,MO-PC, and Ca(PS)2, together with measurements of the Ca2+ concentration in equilibrium with defined PS/PC ratios, enables the determination of the thermodynamic activity of the lipids. The activity coefficient of dilute P,O-PS in PC is analyzed in terms of the partial molal free energy to transfer P,O-PS from an environment of PS to an environment of PC. This study of P,O-PS/MO,MO-PC, by comparison with the earlier study of P,O-PS/P,O-PC [Feigensen, G.W. (1989) Biochemistry 20, 1270-1278], reveals that the excess partial molal free energy to transfer P,O-PS from P,O-PS to P,O-PC is -0.7 kcal mol-1. This free energy change arises in part from the favorable transfer of the negatively charged phosphoserine headgroup from an environment of negative charges to an environment of zwitterions. The contribution of acyl chain mismatch to the partial molal free energy to transfer P,O-PS from P,O-PS to MO,MO-PC is found to be approximately +0.7 kcal mol-1. This value is much larger than that of the excess partial molal free energy of mixing in isotropic solutions of linear hydrocarbons that differ in chain length or unsaturation. PMID- 2252892 TI - Comparison of the orientational order of lipid chains in the L alpha and HII phases. AB - The orientational order profile has been determined by using deuterium nuclear magnetic resonance (2H NMR) for POPE in the lamellar liquid-crystalline (L alpha) and the hexagonal (HII) phases and is shown to be sensitive to the symmetry of the lipid phase. In the HII phase, as compared to the L alpha phase, the acyl chains are characterized by a greater motional freedom, and the orientational order is distributed more uniformly along the lipid acyl chain. This is consistent with a change from a cylindrical to a wedge-shaped space available for the lipid chain. 2H NMR studies of POPE dispersions containing tetradecanol or decane, both of which can induce HII phase structure, show very different behavior. Tetradecanol appears to align with the phospholipid chains and experience the L alpha to HII phase transition with a similar change in motional averaging as observed for the phospholipid chains themselves. In contrast, decane is apparently deeply embedded in the lipid structure and exhibits only a small degree of orientation. The L alpha to HII phase transition for systems containing decane leads to a dramatic increase of the motional freedom of decane which is more pronounced than that observed for the lipid chains. This is consistent with a preferential partition of the decane molecules into a disordered environment such as the intercylinder spaces in the HII phase. The presence of decane in the HII phase structure does not modify the order of the lipid chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252891 TI - 65-kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites. AB - We have previously characterized a 65-kilodalton protein (p65) as an interleukin 2 stimulated phosphoprotein in human T cells and showed that three endopeptide sequences of p65 are present in the sequence of l-plastin [Zu et al. (1990) Biochemistry 29, 1055-1062]. In this paper, we present the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequences and the amino acid composition of cleaved p65 N-terminal peptide indicated that the deduced p65 amino acid sequence exactly coincides with that of l-plastin over the C-terminal 580 residues [Lin et al. (1988) Mol. Cell. Biol. 8, 4659-4668] and has a 57-residue extension at the N terminus to l-plastin. Computer-assisted structural analysis revealed that p65 is a multidomain molecule involving at least three intriguing functional domains: two putative calcium-binding sites along the N-terminal 80 amino acid residues; a putative calmodulin-binding site following the calcium-binding region; and two tandem repeats of putative actin-binding domains in its middle and C-terminal parts, each containing approximately 240 amino acid residues. These results suggest that p65 belongs to actin-binding proteins. PMID- 2252893 TI - Chemiluminescence of the Mn2(+)-activated ribulose-1,5-bisphosphate oxygenase reaction: evidence for singlet oxygen production. AB - Chemiluminescence has been observed during catalysis by Mn2(+)-activated ribulose bisphosphate carboxylase/oxygenase from spinach. The luminescence is ribulose 1,5 bisphosphate (RuBP) and O2-dependent and is inhibited by 2-carboxyarabinitol 1,5 bisphosphate and high concentrations of bicarbonate; it is therefore ascribed to the RuBP oxygenase activity. The luminescence is inhibited by azide and enhanced in D2O and in the presence of diazabicyclooctane. The emission maximum is between 620 and 660 nm. The initial rate of light emission is second order in enzyme concentration. The data strongly suggest that singlet oxygen is produced during turnover, that the observed chemiluminescence is due to dimol emission of singlet oxygen, and that this provides a basis for a highly sensitive assay for RuBP oxygenase. PMID- 2252894 TI - 15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinogen synthase elucidate the structures of enzyme-bound product and a Schiff base intermediate. AB - Porphobilinogen synthase (PBGS) catalyzes the asymmetric condensation of two molecules of 5-aminolevulinic acid (ALA). Despite the 280,000-dalton size of PBGS, much can be learned about the reaction mechanism through 13C and 15N NMR. To our knowledge, these studies represent the largest protein complex for which individual nuclei have been characterized by 13C or 15N NMR. Here we extend our 13C NMR studies to PBGS complexes with [3,3-2H2,3-13C]ALA and report 15N NMR studies of [15N]ALA bound to PBGS. As in our previous 13C NMR studies, observation of enzyme-bound 15N-labeled species was facilitated by deuteration at nitrogens that are attached to slowly exchanging hydrogens. For holo-PBGS at neutral pH, the NMR spectra reflect the structure of the enzyme-bound product porphobilinogen (PBG), whose chemical shifts are uniformly consistent with deprotonation of the amino group whose solution pKa is 11. Despite this local environment, the protons of the amino group are in rapid exchange with solvent (kexchange greater than 10(2) s-1). For methyl methanethiosulfonate (MMTS) modified PBGS, the NMR spectra reflect the chemistry of an enzyme-bound Schiff base intermediate that is formed between C4 of ALA and an active-site lysine. The 13C chemical shift of [3,3-2H2,3-13C]ALA confirms that the Schiff base is an imine of E stereochemistry. By comparison to model imines formed between [15N]ALA and hydrazine or hydroxylamine, the 15N chemical shift of the enzyme-bound Schiff base suggests that the free amino group is an environment resembling partial deprotonation; again the protons are in rapid exchange with solvent. Deprotonation of the amino group would facilitate formation of a Schiff base between the amino group of the enzyme-bound Schiff base and C4 of the second ALA substrate. This is the first evidence supporting carbon-nitrogen bond formation as the initial site of interaction between the two substrate molecules. PMID- 2252896 TI - The rate constant describing slow-onset inhibition of yeast AMP deaminase by coformycin analogues is independent of inhibitor structure. AB - (R)- and (S)-2'-deoxycoformycin, (R)-coformycin, and the corresponding 5' monophosphates were compared as inhibitors of yeast AMP deaminase. The overall inhibition constants ranged from 4.2 mM for (S)-2'-deoxycoformycin to 10 pM for (R)-coformycin 5'-monophosphate, a difference of 3.8 x 10(8) in affinities. (R) Coformycin, (R)-2'-deoxycoformycin 5'-monophosphate, and (R)-coformycin 5' monophosphate exhibited both rapid and slow-onset inhibition. The S inhibitors and (R)-2'-deoxycoformycin exhibited classical competitive inhibition but no time dependent onset of inhibition. The results indicate that the presence of the 2' hydroxyl and 5'-phosphate and the R stereochemistry at the C-8 position of the diazepine ring are necessary for the optimum interaction of inhibitors with yeast AMP deaminase. This differs from the results for rabbit muscle AMP deaminase [Frieden C., Kurz, L. C., & Gilbert, H. R. (1980) Biochemistry 19, 5303-5309] and calf intestinal adenosine deaminase [Schramm, V. L., & Baker, D. C. (1985) Biochemistry 24, 641-646], in which a tetrahedral hydroxyl at C-8 in the R stereochemistry is sufficient for slow-onset inhibition with the coformycins. The results suggest that the transition state contains a tetrahedral carbon with the R configuration as a result of the direct attack of an oxygen nucleophile at C-6 of AMP. Slow-onset inhibition of yeast AMP deaminase is consistent with the mechanism [formula: see text] in which the combination of E and I is rapidly reversible. For these inhibitors, Ki varied by a factor of 3 x 10(3), and the overall inhibition constant (Ki*) varied by a factor of 2 x 10(5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252895 TI - Structure of an acyl-enzyme intermediate during catalysis: (guanidinobenzoyl)trypsin. AB - The crystal and molecular structure of trypsin at a transiently stable intermediate step during catalysis has been determined by X-ray diffraction methods. Bovine trypsin cleaved the substrate p-nitrophenyl p-guanidinobenzoate during crystallization under conditions in which the acyl-enzyme intermediate, (guanidinobenzoyl)trypsin, was stable. Orthorhombic crystals formed in space group P2(1)2(1)2(1), with a = 63.74, b = 63.54, and c = 68.93 A. This is a crystal form of bovine trypsin for which a molecular structure has not been reported. Diffraction data were measured with a FAST (Enraf Nonius) diffractometer. The structure was refined to a crystallographic residual of R = 0.16 for data in the resolution range 7.0-2.0 A. The refined model of (guanidinobenzoyl)trypsin provides insight into the structural basis for its slow rate of deacylation, which in solution at 25 degrees C and pH 7.4 exhibits a t1/2 of 12 h. In addition to the rotation of the Ser-195 hydroxyl away from His-157, C beta of Ser-195 moves 0.7 A toward Asp-189 at the bottom of the active site, with respect to the native structure. This allows formation of energetically favorable H bonds and an ion pair between the carboxylate of Asp-189 and the guanidino group of the substrate. This movement is dictated by the rigidity of the aromatic ring in guanidinobenzoate--model-building indicates that this should not occur when arginine, with its more flexible aliphatic backbone, forms the ester bond with Ser-195. As a consequence, highly ordered water molecules in the active site are no longer close enough to the scissile ester bond to serve as potential nucleophiles for hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252897 TI - Avian alcohol dehydrogenase. Characterization of the quail enzyme, functional interpretations, and relationships to the different classes of mammalian alcohol dehydrogenase. AB - The primary structure of the major quail liver alcohol dehydrogenase was determined. It is a long-chain, zinc-containing alcohol dehydrogenase of the type occurring also in mammals and hence allows judgement of the gene duplications giving rise to the classes of the human alcohol dehydrogenase system. The avian form is most closely related to the class I mammalian enzyme (72-75% residue identity), least related to class II (60% identity), and intermediately related to class III (64-65% identity). This pattern distinguishes the mammalian enzyme classes and separates classes I and II in particular. In addition to the generally larger similarities with class I, the avian enzyme exhibits certain residue patterns otherwise typical of the other classes, including an extra Trp residue, present in both class II and III but not in class I, with a corresponding increase in the UV absorbance. The avian enzyme further shows that a Gly residue at position 260 previously considered strictly conserved in alcohol dehydrogenases can be exchanged with Lys. However, zinc-binding residues, coenzyme-binding residues, and to a large extent substrate-binding residues are unchanged in the avian enzyme, suggesting its functional properties to be related to those of the class I mammalian alcohol dehydrogenases. In contrast, the areas of subunit interactions in the dimers differ substantially. These results show that (a) the vertebrate enzyme classes are of distant origin, (b) the submammalian enzyme exhibits partly mixed properties in relation to the classes, and (c) the three mammalian enzyme classes are not as equidistantly related as initially apparent but suggest origins from two sublevels. PMID- 2252898 TI - Processing of newly synthesized cachectin/tumor necrosis factor in endotoxin stimulated macrophages. AB - The biosynthesis and processing of cachetin/tumor necrosis-factor (TNF) were examined in the murine macrophage-like cell line RAW 264.7. Lipopolysaccharide stimulated cells secreted both glycosylated and nonglycosylated 17-kilodalton (kDa) mature cachectin/TNF into the culture medium. Secreted cachectin/TNF was derived from membrane-associated precursors that were precipitated by polyclonal antisera raised against either the mature protein or synthetic peptide fragments of the 79 amino acid cachectin/TNF prohormone sequence. About half of the precursors were N-glycosylated, apparently cotranslationally. The cachectin/TNF precursors were then proteolytically cleaved to release soluble mature cytokine into the medium, while the membrane-bound 14-kDa presequence remained cell associated. During the period of LPS stimulation, the amount of macrophage cell surface cachectin/TNF remained at a low level, suggesting that both nonglycosylated and glycosylated precursors of cachectin/TNF are efficiently cleaved by these cells. These findings suggest the presence of a unique mechanism for the secretion of cachectin/TNF. PMID- 2252899 TI - Estrogen receptor binding to a DNA response element in vitro is not dependent upon estradiol. AB - Gel shift assays were employed to distinguish between the contribution of 17 beta estradiol (E2) and a short heating step to the ability of the rat uterine cytosolic estrogen receptor (ER) to bind to the estrogen response element (ERE) from the vitellogenin A2 gene (vitERE). Despite the popularity of models in which the ER is a ligand-activated DNA-binding protein, these studies find that estrogen does not significantly contribute to receptor-DNA complex formation. An avidin-biotin complex with DNA (ABCD) assay was utilized to obtain quantitative measurement of the affinities of the ER for the vitERE and a mutant sequence. Scatchard analysis gave a dissociation constant of 390 +/- 40 pM for the E2 occupied, heated ER to the vitERE. The data fit a one-site model and evidence for cooperatively was not observed. A dissociation constant of 450 +/- 170 pM was obtained for the unoccupied, heated ER, leading to the conclusion that estrogen was not necessary for specific binding to DNA. The percentage of ER capable of binding vitERE varied with each cytosol preparation, ranging from 60 to 100% and estrogen did not appear to affect this variation. Competition against the vitERE with a 2-bp mutant sequence showed a 250-fold lower relative binding affinity of the receptor for the mutant over the vitERE sequence. This ability of the ER to discriminate between target and nonspecific DNA sequences was also not dependent on the presence of estrogen. PMID- 2252900 TI - 1H NMR dipolar echo decay spectroscopy: a sensitive probe of membrane structure. AB - The structural and motional properties of membrane lipids in various physical states and macroscopic organizations are elucidated by 1H NMR dipolar echo decay spectroscopy (DECODE). Multilamellar lipid dispersions in the gel (L beta') and liquid-crystalline (L alpha) states and a nonbilayer, hexagonal (HII) phase are readily distinguished, a dynamic profile within these phases is identified, and dipolar order parameters are obtained in the fluid phases. The method is suitable for any pulsed NMR spectrometer. DECODE provides the first depth-dependent assay of lipid order that does not rely on isotopic labeling or exogenous probe. PMID- 2252901 TI - NMR and photo-CIDNP studies of human proinsulin and prohormone processing intermediates with application to endopeptidase recognition. AB - The proinsulin-insulin system provides a general model for the proteolytic processing of polypeptide hormones. Two proinsulin-specific endopeptidases have been defined, a type I activity that cleaves the B-chain/C-peptide junction (Arg31-Arg32) and a type II activity that cleaves the C-peptide/A-chain junction (Lys64-Arg65). These endopeptidases are specific for their respective dibasic target sites; not all such dibasic sites are cleaved, however, and studies of mutant proinsulins have demonstrated that additional sequence or structural features are involved in determining substrate specificity. To define structural elements required for endopeptidase recognition, we have undertaken comparative 1H NMR and photochemical dynamic nuclear polarization (photo-CIDNP) studies of human proinsulin, insulin, and split proinsulin analogues as models of prohormone processing intermediates. The overall conformation of proinsulin is observed to be similar to that of insulin, and the connecting peptide is largely unstructured. In the 1H NMR spectrum of proinsulin significant variation is observed in the line widths of insulin-specific amide resonances, reflecting exchange among conformational substates; similar exchange is observed in insulin and is not damped by the connecting peptide. The aromatic 1H NMR resonances of proinsulin are assigned by analogy to the spectrum of insulin, and assignments are verified by chemical modification. Unexpectedly, nonlocal perturbations are observed in the insulin moiety of proinsulin, as monitored by the resonances of internal aromatic groups. Remarkably, these perturbations are reverted by site specific cleavage of the connecting peptide at the CA junction but not the BC junction. These results suggest that a stable local structure is formed at the CA junction, which influences insulin-specific packing interactions. We propose that this structure (designated the "CA knuckle") provides a recognition element for type II proinsulin endopeptidase. PMID- 2252902 TI - Resonance Raman studies of genetically modified reaction centers from Rhodobacter capsulatus. AB - Resonance Raman (RR) spectra are reported for the photosynthetic reaction center (RC) proteins from Rhodobacter capsulatus wild type and the genetically modified systems GluL104----Leu and HisM200----Leu. The spectra were obtained with a variety of excitation wavelengths, spanning the UV, violet, and yellow-green regions of the absorption spectrum, and at temperatures of 30 and 200 K. The RR data indicate that the structures of the bacteriochlorin pigments in RCs from Rb. capsulatus wild type are similar to those in RCs from Rhodobacter sphaeroides wild type. The data also show that the amino acid modifications near the primary electron acceptor (GluL104----Leu) and special pair (HisM200----Leu) perturb only those bacteriochlorin pigments near the site of the mutation and do not influence the structures of the other pigments in the RC. In the case of the GluL104----Leu mutant, elimination of the hydrogen bond to the C9 keto group of BPhL results in frequency shifts of RR bands of certain skeletal modes of the macrocycle. This allows the assignment of bands to the individual BPhL and BPhM pigments. In the case of the HisM200----Leu mutant, in which the special pair is comprised of a bacteriochlorophyll (BChl)-bacteriopheophytin (BPh) heterodimer rather than the BChl2 unit bound in the wild type, certain skeletal vibrations due to the additional BPh unit are identified. The frequencies of these modes are similar to those of the analogous vibrations BPhL and BPhM, which indicates that the structure of the BPh in the heterodimer is not unusual in any discernible way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2252903 TI - Pulmonary surfactant-associated protein A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro. AB - Although a monolayer of dipalmitoylphosphatidylcholine, the major component of pulmonary surfactant, is thought to be responsible for the reduction of the surface tension at the air-liquid interface of the alveolus, the participation of unsaturated and anionic phospholipids and the three surfactant-associated proteins is suggested in the generation and maintenance of this surface-active monolayer. We have examined the effects of surfactant-associated protein A (SP-A) purified from bovine lavage material on the surface activity of lipid extract surfactant (LES), an organic extract of pulmonary surfactant containing all of the phospholipids and SP-B and SP-C, but lacking SP-A. Measurements of the surface tension during dynamic compression were made on a pulsating bubble surfactometer. Addition of SP-A to LES reduces the number of pulsations required to attain surface tensions near zero at minimum bubble radius. This increase in surface activity is dependent upon the presence of Ca2+ in the assay mixture. Maximal enhancement is observed at or below 1% of the lipid concentration (w/w). The addition of two blood proteins, fibrinogen and albumin, at physiological concentrations to LES causes severe inhibition of surface activity. Addition of SP-A in the presence of Ca2+ completely counteracts the inhibition by fibrinogen. The amount of SP-A required for full reversal of this inhibition was less than 0.5% of the lipid concentration. Complete reversal of inhibition by albumin was also observed, even though there was a approximately 5000-fold molar excess of inhibitor. Addition of lysophosphatidylcholine also inhibits LES; however, SP-A has no effect on this inhibition. PMID- 2252904 TI - DNA sequence dependent binding modes of 4',6-diamidino-2-phenylindole (DAPI). AB - The interactions of DAPI with natural DNA and synthetic polymers have been investigated by hydrodynamic, DNase I footprinting, spectroscopic, binding, and kinetic methods. Footprinting results at low ratios (compound to base pair) are similar for DAPI and distamycin. At high ratios, however, GC regions are blocked from enzyme cleavage by DAPI but not by distamycin. Both poly[d(G-C)]2 and poly[d(A-T)]2 induce hypochromism and shifts of the DAPI absorption band to longer wavelengths, but the effects are larger with the GC polymer. NMR shifts of DAPI protons in the presence of excess AT and GC polymers are significantly different, upfield for GC and mixed small shifts for AT. The dissociation rate constants and effects of salt concentration on the rate constants are also quite different for the AT and the GC polymer complexes. The DAPI dissociation rate constant is larger with the GC polymer but is less sensitive to changes in salt concentration than with the AT complex. Binding of DAPI to the GC polymer and to poly[d(A-C)].poly[d(G-T)] exhibits slight negative cooperativity, characteristic of a neighbor-exclusion binding mode. DAPI binding to the AT polymer is unusually strong and exhibits significant positive cooperativity. DAPI has very different effects on the bleomycin-catalyzed cleavage of the AT and GC polymers, a strong inhibition with the AT polymer but enhanced cleavage with the GC polymer. All of these results are consistent with two totally different DNA binding modes for DAPI in regions containing consecutive AT base pairs versus regions containing GC or mixed GC and AT base pair sequences. The binding mode at AT sites has characteristics which are similar to those of the distamycin-AT complex, and all results are consistent with a cooperative, very strong minor groove binding mode. In GC and mixed-sequence regions the results are very similar to those observed with classical intercalators such as ethidium and indicate that DAPI intercalates in DNA sequences which do not contain at least three consecutive AT base pairs. PMID- 2252905 TI - Color regulation in the archaebacterial phototaxis receptor phoborhodopsin (sensory rhodopsin II). AB - Phoborhodopsin, a repellent phototaxis receptor in Halobacterium halobium, exhibits vibrational fine structure, a feature that has not been identified for any other rhodopsin pigment at physiological temperatures. This conclusion follows form analysis of the absorption properties of the pigment in H. halobium membranes containing native retinal and an array of retinal analogues. The absorption spectrum of the native pigment has a maximum at 487 nm with a pronounced shoulder at 460 nm; however, the bandwidth is that expected for a single retinylidene species. Gaussian band-shape simulation with a spacing corresponding to the vibrational frequencies of polyene stretching modes reproduces the structured absorption spectra of native pigment as well as of analogue phoborhodopsin. Absorption shifts produced by a series of dihydroretinal and other retinal analogues strongly indicate that the dominant factor regulating the color of the pigment is planarization of the retinal ring with respect to the polyene chain. PMID- 2252907 TI - The catalytic site of Escherichia coli aspartate transcarbamylase: interaction between histidine 134 and the carbonyl group of the substrate carbamyl phosphate. AB - Previous pKa determinations indicated that histidine 134, present in the catalytic site of aspartate transcarbamylase, might be the group involved in the binding of the substrate carbamyl phosphate and, possibly, in the catalytic efficiency of this enzyme. In the present work, this residue was replaced by an asparagine through site-directed mutagenesis. The results obtained show that histidine 134 is indeed the group of the enzyme whose deprotonation increases the affinity of the catalytic site for carbamyl phosphate. In the wild-type enzyme this group can be titrated only by those carbamyl phosphate analogues that bear the carbonyl group. In the modified enzyme the group whose deprotonation increases the catalytic efficiency is still present, indicating that this group is not the imidazole ring of histidine 134 (pKa = 6.3). In addition, the pKa of the still unknown group involved in aspartate binding is shifted by one unit in the mutant as compared to the wild type. PMID- 2252906 TI - Organization of glycosphingolipids in phosphatidylcholine bilayers: use of antibody molecules and Fab fragments as morphologic markers. AB - The techniques of ultrafast freezing and freeze-etch electron microscopy have been successfully employed to visualize IgG molecules and Fab fragments specifically bound to the neutral glycosphingolipids Forssman and asialo-GM1 incorporated into phosphatidylcholine liposomes. Monovalent Fab is the superior marker because of its small size and because it does not cause liposomal aggregation with concomitant glycolipid reorganization. Analysis of Fab labeling of liposomes containing these neutral glycosphingolipids leads to the conclusion that the Forssman glycosphingolipid is dispersed in clusters of not more than several molecules when present at low mole fraction in fluid-phase 1-palmitoyl-2 oleoylphosphatidylcholine liposomes. In contrast to this, asialo-GM1 under the same conditions is present in clusters of about 15 molecules in this phospholipid matrix. PMID- 2252909 TI - Lipid transport function of lipoproteins in flying insects. PMID- 2252908 TI - Interactions between G-actin and myosin subfragment 1: immunochemical probing of the NH2-terminal segment on actin. AB - The role of the N-terminal segment of actin in myosin-induced polymerization of G actin was studied by using peptide antibodies directed against the first seven N terminal residues of alpha-skeletal actin. Light scattering, fluorescence, and analytical ultracentrifugation experiments showed that the Fab fragments of these antibodies inhibited the polymerization of G-actin by myosin subfragment 1 (S-1) by inhibiting the binding of these proteins to each other. Fluorescence measurements using actin labeled with pyrenyliodoacetamide revealed that Fab inhibited the initial step in the binding of S-1 to G-actin. It is deduced from these results and from other literature data that the initial contact between G actin and S-1 involves residues 1-7 on actin and residues 633-642 on the S-1 heavy chain. This interaction appears to be of major importance for the binding of S-1 and G-actin. The presence of additional myosin contact sites on G-actin was indicated by concentration-dependent recovery of S-1 binding to G-actin without displacement of Fab. The reduced Fab inhibition of S-1 binding to polymerizing and polymerized actin is consistent with the tightening of acto-S-1 binding at these sites or the creation of new sites upon formation of F-actin. PMID- 2252910 TI - Fatty acid binding protein in flight muscle of the locust, Schistocerca gregaria. AB - The cytosol of flight muscle from the adult desert locust, Schistocerca gregaria, contains a fatty acid binding protein (FABP). Locust FABP has a molecular weight of 15,000 and an isoelectric point of 5.2. It binds fatty acids stoichiometrically in a 1:1 ratio. Its molecular characteristics, tissue specificity and electrophoretic behavior are reminiscent of mammalian M-FABP. Compared to its mammalian counterpart, the cytosolic concentration is much higher, reflecting the high rate of fatty acid oxidation observed during locust flight. Our discovery, showing for the first time an FABP in an invertebrate species, supports the proposed function of muscle FABP as intracellular fatty acid receptor or transport protein. PMID- 2252911 TI - Identification of novel hydroxy fatty acids in the barnacle Balanus balanoides. AB - The ability of the barnacle Balanus balanoides tissues to produce eicosanoid hatching factors from endogenous polyunsaturated fatty acids has been investigated. GC-MS analysis of an active HPLC fraction from the trihydroxy fatty acid band on TLC revealed the presence of a number of trihydroxy fatty acids and two compounds which were tentatively identified as chlorinated dihydroxy fatty acids. The identified trihydroxy fatty acids are 10,11,12-trihydroxy-5,8,14 eicosatrienoic acid, 10,11,12-trihydroxy-5,8,14,17-eicosatetraenoic acid, 13,14,15-trihydroxy-5,8,11,17-eicosatetraenoic acid and 12,13,14-trihydroxy 4,7,10,16,19-docosapentaenoic acid. The tentatively identified chlorinated dihydroxy fatty acids are 9-chloro- and/or 11-chloro-8,12 dihydroxyeicosatetraenoic acid. The formation of these compounds is evidence of lipoxygenase activities in Balanus balanoides and their identification will facilitate the understanding of the roles eicosanoids play in barnacle physiology, especially with regard to the larval hatching process. PMID- 2252912 TI - Cholesterol: free radical peroxidation and transfer into phospholipid membranes. AB - Cholesterol, when sequestered in saturated liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC), undergoes peroxidation thermally initiated either by a lipid-soluble or a water soluble azo initiator and in both cases the reaction is inhibited effectively by the water-soluble antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox). Quantitative kinetic methods of autoxidation show that the oxidizability, kp/(2kt)1/2 (where kp and 2kt are the rate constants of radical chain propagation and termination, respectively) of cholesterol in DMPC or DPPC multilamellar liposomes, where kp/(2kt)1/2 is 3.0.10(-3) to 4.3.10(-3) M-1/2 s 1/2 at 37-45 degrees C, is similar to that measured in homogeneous solution in chlorobenzene, where kp/(2kt)1/2 is 3.32.10(-3). However, its oxidizability in smaller unilamellar vesicles of DMPC or DPPC increases by at least 3-times that measured in multilamellar systems. Autoxidation/antioxidant methods show that cholesterol partitions directly from the solid state into DMPC or DPPC liposomes by shaking and this is confirmed by 31P and 2H quadrupole NMR spectra of deuterated cholesterol when membrane bound. Analytical studies indicate that up to 21 mol% cholesterol will partition into the membranes by shaking. PMID- 2252913 TI - Purification and characterization of a soluble phospholipase A2 from guinea pig lung. AB - Guinea pig lung cytosolic phospholipase A2 was purified to near homogeneity by chromatography on a phosphocellulose column, followed by Q-Sepharose, S Sepharose, gel filtration chromatography and reverse-phase HPLC. The purified enzyme exhibited an apparent molecular weight of 16,700 by SDS-polyacrylamide gel electrophoresis. Active enzyme eluted from the gel at an apparent molecular weight of 16,700. The purified enzyme exhibited a pH optimum of 9.0 and was calcium-dependent. Guinea pig lung phospholipase A2 hydrolyzed phosphatidylcholine and phosphatidylethanolamine equally well. Substrates containing unsaturated fatty acids in the sn-2 position were hydrolyzed preferentially to those containing saturated fatty acids. Anionic detergents stimulated enzyme activity while nonionic detergents inhibited the enzyme. Disulfide reducing agents dithiothreitol, glutathione and 2-mercaptoethanol modestly stimulated enzyme activity. The sulfhydryl aklylating agent n ethylmaleimide had no effect on enzyme activity and only high concentrations of p hydroxymercuribenzoic acid inhibited enzyme activity. The histidine modifying agent, bromophenacyl bromide did not inhibit guinea pig lung phospholipase A2 under conditions in which Crotalus adamanteus phospholipase A2 was inhibited 80%. Manoalide inhibited guinea pig lung phospholipase A2 in a concentration-dependent manner (IC50 = 2 microM). Antibodies prepared against porcine pancreatic phospholipase A2 specifically immunoprecipitated guinea pig lung phospholipase A2 suggesting that the major phospholipase A2 in guinea pig lung cytosol is immunologically related to pancreatic phospholipase A2 in agreement with the biochemical properties of the enzyme. PMID- 2252914 TI - Surface properties of two rabbit lung lamellar body preparations with markedly different fatty acid profiles. AB - The effect of fatty acid desaturation on the surface properties of lung surfactant were studied on a Wilhelmy surface balance by using two preparations of lamellar body (LB) material with markedly different fatty acid profiles: (1) lamellar bodies from adult rabbit lung tissue, and (2) lamellar bodies from fetal rabbit lung tissue maintained in organ culture for 7 days. The fetal lung preparation contains an unusually high level of 16: 1 fatty acid (principally palmitoleic acid) at position sn-2 of phosphatidylcholine (Longmuir, K.J., Resele Tiden, C. and Rossi M.E. (1988) J. Lipid Res. 29, 1065-1077). Surface pressure surface area isotherms were obtained for both preparations and compared to isotherms of monolayers of dipalmitoylphosphatidylcholine. In addition, the elasticity of the lamellar body preparations were analyzed as a function of surface pressure, temperature, and rate of compression, both in the presence and absence of Ca2+ plus Mg2+. At slow rates of compression, we found that fetal LB films have lower elasticity and better respreading ability compared to the adult LB films, which can be explained by the high concentration of unsaturated palmitoleic acid in the fetal preparation. A dynamic component of elasticity was observed at high rates of compression only if Ca2+ and Mg2+ were present in the subphase. The analysis of the free energies, enthalpies and entropies of compression suggests that films with low concentrations of unsaturated fatty acids are are likely to undergo irreversible collapse, but films with excess unsaturated fatty acids accommodate the overcompression with a reversible loss of molecules from the surface. PMID- 2252915 TI - Effect of the methylation inhibitors 3-deazaadenosine and 3-deazaaristeromycin on phosphatidylcholine formation in Tetrahymena. AB - The methylation inhibitors 3-deazaadenosine and 3-deazaaristeromycin inhibited the methylation pathway for phosphatidylcholine formation in Tetrahymena. At the same time, the phosphatidylcholine levels within the cell were maintained by increased use of the phosphotransferase pathway. Cell growth was not affected at inhibitor concentrations up to 50 microM but was 50% inhibited at inhibitor concentrations of 100 microM. This growth inhibition was not reversed by the addition of choline to the growth medium. The added choline resulted in greater use of the phosphotransferase pathway, even in uninhibited cultures, but there was no effect on phosphatidylcholine levels, pointing to a much tighter control on phosphatidylcholine formation than exists in animal cells. PMID- 2252916 TI - Sodium oleate dissociates the heteroexchange of cholesteryl esters and triacylglycerol between HDL and triacylglycerol-rich lipoproteins. AB - Mixtures of human high-density lipoproteins (HDL) and triacylglycerol-rich lipoproteins (TGRL) have been incubated in the presence of partially pure cholesteryl ester transfer protein (CETP). There were net mass transfers of cholesteryl ester from HDL to TGRL and of triacylglycerol from TGRL to HDL which were accompanied by the formation of minor subpopulations of small HDL particles. When the mixture of HDL, TGRL and CETP was supplemented with fatty acid-poor bovine serum albumin (40 mg/ml) there was a 7% reduction in the transfer of cholesteryl esters out of HDL (P less than 0.05) and a 14% increase in the transfer of triacylglycerol into HDL (P less than 0.05); there was also a reduction in the formation of very small HDL particles. In contrast, when the mixture of HDL, TGRL and CETP was supplemented with 0.16 mM sodium oleate the transfer of cholesteryl esters out of HDL was increased by 31% (P less than 0.001) and the transfer of triacylglycerol into HDL was decreased by 25% (P less than 0.01); under these conditions the formation of very small HDL particles was enhanced. It has been concluded that in the presence of sodium oleate, there is a dissociation of the CETP-mediated heteroexchange of cholesteryl esters and triacylglycerol between HDL and TGRL. PMID- 2252917 TI - Changes in the law on abortion. PMID- 2252918 TI - Recurrent hereditary polyserositis. PMID- 2252919 TI - The fetal and infant origins of adult disease. PMID- 2252920 TI - Changing view of prognosis of epilepsy. PMID- 2252921 TI - Socioeconomic conditions in childhood and ischaemic heart disease during middle age. AB - OBJECTIVE: To examine the association between socioeconomic conditions in childhood and ischaemic heart disease in middle aged men, including the role of physiological and behavioural risk factors. DESIGN: Prevalence study with extensive examination and testing and with recall of childhood conditions. SETTING: Population based study in Kuopio, Finland. SUBJECTS: Representative sample of 2679 men aged 42, 48, 54, and 60. MAIN OUTCOME MEASURES: Ischaemic findings on progressive maximal exercise test. RESULTS: Low socioeconomic style in childhood was associated with significantly higher prevalence of findings indicating ischaemias. Compared with those in the highest tertile of childhood socioeconomic conditions, the age adjusted odds ratio for subjects in the lowest tertile was 1.44 and for those in the middle tertile 1.35. Adjustment for years of cigarette smoking times the average number of cigarettes smoked, ratio of high density lipoprotein to low density lipoprotein cholesterol, fibrinogen and serum selenium concentrations, and adult height did not appreciably weaken the association. Adjustment for adult socioeconomic state resulted in a 16% decline in the association. The association was reduced to non-significance by adjustment for measures of prevalent cardiovascular illness. CONCLUSIONS: Socioeconomic state in childhood was significantly associated with ischaemic heart disease in middle aged men. Levels of risk factors measured at middle age did not account for this association, nor did adult height. Because childhood socioeconomic conditions precede the development of ischaemic heart disease the substantial impact of prevalent illness on the observed association suggests that ischaemic heart disease develops earlier in those with lower socioeconomic state during childhood. PMID- 2252922 TI - Famine in southern Ethiopia 1985-6: population structure, nutritional state, and incidence of death among children. AB - OBJECTIVE: To assess the effects of drought on mortality in children. DESIGN: Prospective epidemiological study forming part of nutritional monitoring during famine relief work. SETTING: 24 Food distribution sites in Arero and Borana provinces in southern Ethiopia. PATIENTS: A monthly average of 14,173 and 5,334 children under 5 were examined in 1985 and 1986, respectively. Altogether 148,966 child months (105,872 for 1985 and 43,094 for 1986) were available for analysis. INTERVENTION: The families of all children were supplied with food each month. Basic medical care was also provided. MAIN OUTCOME MEASURE: Mortality in children under 5. RESULTS: A 40% increase in crude mortality was observed among children living in traditional and stable societies. The severe consequences were observed mainly among children living in relief shelters, where a threefold to fourfold increase in crude mortality was recorded among children. Increased childhood mortality was also associated with high prevalence of malnutrition, living in the most arid areas, and the dry season. A long period of food aid was needed to normalise the nutritional state, especially for children living in relief shelters. CONCLUSIONS: The most severe consequences of the widespread famine that occurred in the Arero and Borana provinces of southern Ethiopia during 1985-6 were seen among children living in relief shelters. Early food intervention may decrease the scale of migration and thus also reduce the severe consequences of a famine. PMID- 2252923 TI - Long term survival after intensive care. AB - OBJECTIVE: To examine the long term survival of critically ill patients admitted to an intensive therapy unit and to ascertain the effects of age, severity of illness, and diagnostic category at admission on survival. DESIGN: Retrospective observational study with prospectively gathered data on all patients admitted to the unit between June 1985 and July 1987 and followed up until 1 January 1989. SETTING: Regional intensive therapy unit. PATIENTS: 513 critically ill adult patients, 16 of whom were excluded because measurements on severity of illness scoring were not available. MAIN OUTCOME MEASURES: Age, severity of illness (determined with the acute physiology and chronic health evaluation (APACHE) II score), and diagnostic category on admission; deaths in the unit; and long term survival after discharge. Details of the survivors were sent to the Registrar General for Scotland, who issued copies of death certificates for the patients who had died between discharge and 1 January 1989. RESULTS: Of 497 patients, 119 (24%) died in the intensive therapy unit and 120 (24%) after discharge, leaving 258 (52%) who were still alive at two years. The median (APACHE II) score was 13 and about half of the patients were aged 55 years or more. A wide range of critical illnesses, except neurosurgical emergencies, were treated. Survival analysis showed that only 41 (34%) of 122 patients with an APACHE II score of greater than or equal to 20 were alive at one year (95% confidence interval 25 to 42) compared with 124 (80%) of 155 patients with a score of less than 10 (73 to 87). Of the 144 patients aged 65 or more, only 68 (47%) survived to one year (39 to 55) but 90 (83%) of the 109 patients aged between 18 and 34 survived a similar period (76 to 71). Mortality was also related to diagnostic category; 71% of trauma victims survived to one year compared with only 41% of those admitted with gastrointestinal pathology. Univariate analysis of the results showed that age, severity of illness, and diagnosis were all predictors of long term survival. Multivariate analysis, however, showed that only age and severity of illness were independent prognostic factors. CONCLUSIONS: Long term survival of patients treated in an intensive therapy unit is related to severity of illness and to age. The outcome from critical illness in the elderly population is poor. PMID- 2252924 TI - Women in prison and use of illicit drugs before arrest. PMID- 2252925 TI - Are readmissions avoidable? AB - OBJECTIVE: To examine the possible use of readmission rates as an outcome indicator of hospital inpatient care by investigating avoidability of unplanned readmissions within 28 days of discharge. DESIGN: Retrospective analysis of a stratified random sample of case notes of patients with an unplanned readmission between July 1987 and June 1988 by nine clinical assessors (263 assessments) and categorisation of the readmission as avoidable, unavoidable, or unclassifiable. SETTING: District in North East Thames region. 481 General medical, geriatric, and general surgical inpatients with a readmission at 0-6 days or 21-27 days after the first (index) discharge between July 1987 and June 1988 from whom 100 case notes were selected randomly and of which 74 were available for study. MAIN OUTCOME MEASURES: Assessment of readmissions as avoidable, unavoidable, unclassifiable, variability of assessment within cases and variability among assessors according to specialty and duration to readmission. RESULTS: General medical and geriatric readmissions and surgical readmissions at 0-6 days after discharge were more likely to be assessed as avoidable than those at 21-27 days (medical readmissions 32 v 6%, surgical admissions 49 v 19%). General surgical readmissions were significantly more frequently assessed as avoidable than general medical and geriatric readmissions. The extent of agreement between doctors varied, with general medical and geriatric readmissions at 21-27 days after first discharge causing the greatest variability of judgment. CONCLUSIONS: Differences were apparent in the extent of avoidability of readmissions in different groups of admissions. However, assessors rated only 49.3% of the group with the highest proportion of avoidable admissions (surgical readmissions at 0-6 days) as avoidable. The remainder were thought to be unavoidable except for 2%, which could not be classified. The use of readmission rates as an outcome indicator of hospital inpatient care should be avoided. PMID- 2252926 TI - Can readmission rates be used as an outcome indicator? PMID- 2252927 TI - Management of "brittle" diabetes with a preprogrammable implanted insulin pump delivering intraperitoneal insulin. AB - OBJECTIVE: Glycaemic control in a young woman with "brittle" diabetes. DESIGN: Use of a preprogrammable fully implanted pump (Infusaid) to deliver insulin intraperitoneally at variable rates, giving a total dose of about 60 units/24 h. SETTING: Endocrinology department in a teaching hospital. PATIENT: Thirty year old woman with 15 years' history of "brittle" diabetes. MAIN OUTCOME MEASURES: Glycated haemoglobin concentration; plasma glucose concentration. RESULTS: After implantation of the pump there was an immediate and sustained improvement in diabetic control. The patient's glycated haemoglobin concentration decreased from 15.2% to 9.2% over seven months. Her daily glucose concentrations were in the range 3.5-12 mmol/l. She has not been admitted to hospital since implantation of the pump, which was eight months before the time of writing. CONCLUSION: The implanted programmable intraperitoneal insulin pump may be of value in the management of patients with "brittle" diabetes in whom other attempts at glycaemic control have failed. PMID- 2252928 TI - ABC of major trauma. Handling distressed relatives and breaking bad news. PMID- 2252929 TI - Aids for visual impairment. AB - This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue. PMID- 2252930 TI - Tale of two hospitals. PMID- 2252931 TI - Long term reduction in sodium balance. PMID- 2252932 TI - Forensic pathology. PMID- 2252933 TI - Carbon monoxide poisoning in the home. PMID- 2252934 TI - Diabetic autonomic neuropathy. PMID- 2252935 TI - Guidelines for management of asthma. PMID- 2252936 TI - Trauma in pregnancy. PMID- 2252937 TI - How easy is it to contact the duty doctor responsible for admissions? PMID- 2252938 TI - Diagnosing cancer of the pancreas. PMID- 2252939 TI - Potassium and magnesium in essential hypertension. PMID- 2252940 TI - Management of intercostal drains. PMID- 2252941 TI - Nobel prizes given for clinical research. PMID- 2252942 TI - Treatment of viral pharyngitis or flu. PMID- 2252943 TI - Behavioural and cognitive-behavioural treatments for epilepsy: a progress review. AB - Epilepsy is increasingly being viewed as a condition where psychological interventions may offer great potential in bringing about a reduction in the frequency of seizures. Early studies of behavioural interventions (including classical and operant conditioning approaches) designed to reduce seizure frequency were often subject to considerable methodological flaws. The outcome of recent behavioural and cognitive-behavioural treatment trials is reviewed in the light of criticisms of earlier studies. Persisting methodological difficulties are discussed and recommendations made for future studies. PMID- 2252944 TI - Coping and help-seeking in the UK adult population. AB - A large national sample of the UK adult population was surveyed to find out how respondents would cope and whom they would turn to for help if they experienced psychological problems. Overall, the most frequently endorsed coping methods were cognitive or behavioural rather than avoidance- or substance-based. Respondents tended to endorse informal rather than formal helpers, especially partners and close relatives, although the family doctor was given greater endorsement than in corresponding US studies. Individual differences in coping and help seeking were examined with respect to demographic variables and level of reported psychological symptoms. Respondents who reported higher levels of symptoms tended to endorse more coping methods, especially avoidance methods, and to show greater readiness to seek help. The implications of the findings for traditional clinical work and for mental health education and promotion are discussed. PMID- 2252945 TI - Group counselling for relatives of hospitalized presenile dementia patients: a controlled study. AB - A controlled study is reported in which the effects of time-limited group counselling for the relatives of hospitalized presenile dementia patients is evaluated. The results indicate that such group counselling was effective in increasing relatives' morale, increasing their knowledge about dementia, and increasing the number of activities performed with the patient during visits, but had no effect upon the frequency or duration of visits or the amount of verbal and non-verbal communication between patient and relative. All changes achieved were maintained at three month follow-up. PMID- 2252947 TI - The relationship between the Eysenck Personality Questionnaire and Beck's concepts of sociotropy and autonomy. PMID- 2252946 TI - Young adult offspring of parents with drinking problems: recollections of parents' drinking and its immediate effects. AB - One hundred and seventy 16- to 35-year-old offspring of parents with drinking problems were recruited from a variety of clinical and community sources and each was interviewed at length using a semi-structured interview. The present paper focuses upon carefully reconstructed recollections of childhood, and presents quantitative information from the whole sample and three briefly described individual examples. Large variances on quantitative measures and very varied qualitative accounts of childhood were evident. The large majority described parental drinking problems which spanned their childhood and adolescent years without interruption and without treatment. Amongst the most frequently recalled effects on life at home were parental moodiness, unreliability, and a tendency to upset or fail to join in with family activities. Amongst negative childhood experiences recalled most frequently were worry and uncertainty, a feeling of family instability, the experience of being caught between the interests of two parents, and the adoption of certain adult roles. Those with mothers with drinking problems scored significantly higher on a scale of negative childhood experiences and mothers with drinking problems were more likely to have drunk regularly at home. Those offspring from families of higher social status estimated their parental problems to have started slightly later in childhood. Qualitative analysis suggested that whether excessive parental drinking is perceived as alien to or integral with family life may have been a neglected variable. PMID- 2252948 TI - Eating disorders, perceived control, assertiveness and hostility. AB - There are anecdotal claims that eating disorder patients perceive themselves as highly controlled by the family and by society, but that they do not show assertive behaviour towards controllers. Anorexic and bulimic females were compared with female psychiatric patients, dieters and non-dieting controls on measures of eating disorder symptomatology, locus of control, assertiveness, inwardly directed hostility, family control and family encouragement of independence. Eating disorder patients reported significantly more external control, more inwardly directed hostility, less self-assertion and less family encouragement of independence than dieters and non-dieting controls, but they did not differ from psychiatric controls. Most of the characteristics seen in eating disorder subjects were also reported by psychiatric controls. PMID- 2252949 TI - Factors underlying a psychiatric day hospital consumer survey. AB - The results of a recently reported consumer survey were further examined by means of a factor analysis. Two factors emerged: the major one reflecting the general perceived helpfulness of the day hospital, and a secondary one which correlated positively with the rated helpfulness of talking to nurses and negatively with the helpfulness of medication. Day attenders who rated talking with nurses as more helpful showed a greater tendency to be married with children. PMID- 2252950 TI - Clinical depression and attributional complexity. AB - Recent research on attributional complexity with college student samples has indicated that mild and moderate depression are associated with increased attributional complexity but more severe depression may be related to decreased attributional complexity. The present study examined levels of attributional complexity in clinically depressed patients and normal controls. The results confirmed that severe depression is associated with reduced attributional complexity. The results are discussed in terms of the need for a multidimensional model of attribution and depression that incorporates individual differences in variables such as attributional complexity. PMID- 2252951 TI - External attributions and outcome in depressive in-patients. AB - Thirty-four voluntarily admitted depressive in-patients were asked by their clinicians in the first interview why they came into hospital and what they expected there. Some patients expressed external attributions referring to other persons who were viewed as being responsible for the admission or for improvement under treatment. External attributions of this kind were found to have some negative predictive value for the outcome of treatment. PMID- 2252952 TI - Psychological and psychophysiological characteristics in irritable bowel syndrome. AB - Psychiatric disorder is reported to occur in a large proportion of patients with irritable bowel syndrome (IBS) and psychological treatment methods have been advocated for this patient group. In a sample of 25 out-patients with intractable IBS, only four patients with psychiatric disorder were identified. The majority did not have elevated levels of anxiety or depression nor was there evidence of significant abnormal illness behaviour. Electrodermal activity did not show the extremes of responding and habituation associated with anxiety, depression or chronic pain. It is suggested that, when accurate diagnostic criteria are employed, a specific relationship between IBS and psychopathology is no longer evident. PMID- 2252953 TI - Dieting concerns of 10-year-old girls and their mothers. AB - The responses of a group of 10-year-old girls on a dietary restraint questionnaire described a wide range of dieting concerns. Subgroups of highly restrained and low-restrained girls were identified and their mothers interviewed. A strong relationship (r = .68) was found between the degree of dietary restraint expressed by the girls and their mothers. The highly restrained girls had a significantly higher EAT score than the low-restrained girls, and shared with their mothers a susceptibility to the disinhibitory effects of negative mood states on their eating behaviour. PMID- 2252954 TI - The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? AB - Graft-versus-leukemia (GVL) is a major component of the overall beneficial effects of allogeneic bone marrow transplantation (BMT) in the treatment of leukemia. Although several clinical trials have suggested a direct relationship between GVL effects and acute and chronic graft-versus-host disease (GVHD), it is not yet known whether GVL can be separated from GVHD. However, several investigations in murine models of human leukemia indicate that the two may be at least partially separable. Moreover, analysis of clinical data from the International Bone Marrow Transplant Registry suggest that allogeneic BMT may be more advantageous than syngeneic BMT, regardless of the GVHD. Likewise, T lymphocyte depletion is associated with an increased incidence of relapse, independently of GVHD. Recent investigations in murine leukemia suggest that GVL like effects may be inducible following syngeneic BMT by recombinant cytokines with no overt GVHD. Taken together, current data in experimental animals and man suggest that GVL may be at least partially separable from GVHD. Hence, further understanding of effector and target cells of GVL as well as our ability to induce antitumor effector cells, especially those that are MHC nonrestricted, may lead to new approaches for potentiating anti-tumor effector mechanisms without inducing severe, clinically overt GVHD. Successful attempts in these directions may also lead to improved results following autologous BMT as a result of activation of GVL-like effects by recombinant cytokines that are capable of activating effector cells with anti-leukemic activity in vivo, such as recombinant human IL2, alpha interferon or perhaps a synergistic combination of factors. PMID- 2252955 TI - High efficiency of a new immunological magnetic cell sorting method for T cell depletion of human bone marrow. AB - Fresh human bone marrow (BM) mononuclear cells containing a mean of 11% T cells underwent T cell depletion utilizing a newly developed magnetic cell sorter. In order to remove T cells, 10(8) cells were labeled with either a specific CD3 monoclonal antibody or a cocktail of monoclonal CD2 + CD5 + CD7 antibodies and biotin-conjugated magnetic microparticles (size 100-150 nm) employing a streptavidin-FITC complex. Labeled cells were removed by using columns filled with a ferromagnetic matrix and placed within a recess in a strong permanent magnet. Recovery of non-T cells was 79% after the first passage and 61% after the second. The absolute recovery of BFU-E and CFU-GM was 70% and 51% respectively (n = 11). Limiting dilution analysis revealed less than 0.1% residual clonable BM T cells (cloning efficiency greater than 50%) which corresponds to a 2.1 (1st passage) and to a 2.3 (2nd passage) log depletion. This new separating system is a highly efficient, reproducible, and quick method of depleting T cells from human BM. It could be easily adapted to process large scale marrow specimens or for the elimination of residual tumor cells from BM in autologous transplantation. PMID- 2252956 TI - Lymphokine-activated killer (LAK) cell purging of leukemic bone marrow: range of activity against different hematopoietic neoplasms. AB - Natural killer cells activated in vitro by incubation with IL-2 display a broad range of cytolytic activity against neoplastic cells. These lymphokine-activated killer (LAK) cells can discriminate between neoplastic and normal bone marrow cells and may represent a useful means of purging bone marrow prior to autologous transplantation. We demonstrate that LAK cells can successfully remove four distinctly different malignant hematopoietic cell types from normal bone marrow grafts. The LAK purging technique is capable of a 2-3 log10 reduction in tumor cells in the bone marrow graft without compromising hematological recovery or survival. Our results also suggest, however, that an inhibitory effect on stem cell function by allogeneic LAK cells exists, and this form of purging may be used only if greater levels of bone marrow are transferred in an allogeneic setting. The ability to detect and eliminate malignant cells in bone marrow prior to use for autologous transplantation suggests that LAK cells, alone or in conjunction with current methods of bone marrow purging, could be useful for the in vitro treatment of bone marrow in patients who require high-dose chemotherapy and autologous bone marrow transplantation. PMID- 2252957 TI - Levels of detection of tumor cells in human bone marrow with or without prior culture. AB - With an in vitro culture technique combined with light microscopy, immunocytochemistry and molecular probing, we previously detected occult tumor cells in histologically-normal human bone marrow harvested for autologous transplantation. In this study, we mixed known numbers of malignant lymphoid (Raji and CEM) or breast cancer (MCF-7) cells with normal human bone marrow cells to determine the levels at which tumor cells can be detected before and after culture. Cytocentrifuge preparations were made before culture and after 2 or more weeks of culture and examined by light microscopy. We detected contaminating lymphoma cells at a level of more than 5% before culture, and at a level of 0.01% after culture for 2 or more weeks in 2% human lymphocyte conditioned medium. Before culture, we detected MCF-7 cells at a level of 0.001% using glucose oxidase immunocytochemical staining techniques; these cells were detected at a level of 0.00001% after culture. Since, of necessity, these calibrations rations were performed using cell lines, it is likely that these results overestimate the absolute sensitivity of these methods for detection of tumor cells in patient samples. We found the glucose oxidase immunocytochemical method more specific for detecting occult tumor cells in bone marrow than the immunoperoxidase staining method because of the absence of non-specific staining arising from endogenous peroxidase in bone marrow cells which makes the interpretation of the latter difficult. We conclude that culture techniques can increase the sensitivity of detection of occult tumor cells in human bone marrow about 100-fold. PMID- 2252959 TI - A novel approach to purging of leukemia by activation of bone marrow with interleukin 2. AB - The cytotoxic potential of interleukin 2 (IL-2) activated bone marrow (ABM) was compared with that of IL-2 activated peripheral blood lymphocytes (LAK cells) against three hematologic tumor cell lines (K-562, CEM, Daudi) and fresh lymphoid blasts in short-term chromium release assays. ABM was found to be superior to LAK cells against all tumor cells tested. The recovery of bone marrow (BM) cells dropped with passage of time in culture but their clonogenic potential was not impaired (with or without IL-2). BM contaminated with CEM cells and treated with IL-2 showed significant ability to purge itself of the leukemic cells in semisolid agar culture; the purging ability of 3- and 1-day ABM was comparable. IL-2 alone or BM alone had no influence on the growth of CEM cells. This study suggests that BM can be activated with IL-2 in vitro to generate the ability to eliminate contaminating leukemic cells without affecting its progenitor cell function in vitro. PMID- 2252958 TI - Patients at increased risk for late engraftment after transplantation: a novel method for their identification. AB - The time to platelet engraftment (platelets greater than 50 x 10(9)/l for 3 successive days without transfusions) is a major endpoint in treatment regimens of high dose chemotherapy and autologous stem cell rescue. A number of transplanted patients die before recovery of platelets. To include such patients appropriately in an analysis to identify prognostic factors for engraftment, a proportional odds model was employed. The outcome measure was a categorization of patients into four levels based on time to engraftment: early (0-40 days), intermediate (41-70 days), late (greater than 70 days) or died without engraftment. Of 45 women with advanced breast cancer who underwent high dose chemotherapy and autologous transplantation, there were: 10 early, 11 intermediate and eight late engrafters and 16 who died before platelet engraftment. Based on the proportional odds model applied to these data, four significant and independent prognostic factors for later or non-engraftment were revealed: lower numbers of mononuclear cells/kg harvested (p = 0.002), lower serum albumin level (p = 0.003), prior cisplatin chemotherapy (p = 0.006), and the existence of bone marrow malignancy (p = 0.025). PMID- 2252960 TI - Use of an immunoglobulin preparation enriched for IgM (Pentaglobin) for the treatment of acute graft-versus-host disease. AB - Pentaglobin is a commercial immunoglobulin preparation which is enriched specifically for IgM and also contains antibodies that are capable of neutralizing endotoxins. Its potential use in treating patients with acute graft versus-host disease (GVHD) was studied in a phase I/II study. Pentaglobin was administered at a dose of 8 ml/kg/day for 4 days as a continuous infusion to 10 patients after allogeneic marrow transplantation who had histologically documented moderate grade II (n = 8) or moderately severe acute GVHD grade III (n = 2), and who did not require immediate treatment with steroids. There were no side effects related to the infusion of Pentaglobin and in all cases the serum concentrations of IgA, IgG and IgM at least doubled. Improvement of GVHD was seen in five patients with grade II GVHD. Conversely, in three patients with grade II and two patients with grade III GVHD, the disease either progressed during Pentaglobin infusion and required steroid treatment or showed no change and required steroids later in the course. Pentaglobin, therefore, might have some effect on mild and moderate GVHD. Randomized trials should be able to determine whether Pentaglobin could be considered as part of the GVHD prophylaxis or as adjunct treatment for acute GVHD together with low doses of steroids. PMID- 2252961 TI - Processing and storage of human bone marrow: a survey of current practices in North America. AB - We conducted a two-step survey to question 110 transplant centers in the United States and Canada regarding marrow processing and storage policies and procedures. Approximately 65% of the centers surveyed responded to the questionnaires. Major differences with respect to patient diagnoses, amount of marrow harvested, purging method applied, freezing procedure, storage bag, cell concentrations, storage duration, interval until transplantation, cell counting, viability determination and so forth were reported. Among those centers responding 13% stored not only autologous but also allogeneic marrow. There was no consensus regarding patient consent for duration of storage, coverage of cost for cryopreservation or utilization of stored marrow after a patient's death. Additional studies will be necessary to correlate in vitro methods of marrow storage with clinical transplantation results, and to determine the cost/benefit ratio of this approach to various diagnoses. This should provide the basis for the establishment of standards and should facilitate the approach to various ethical questions. PMID- 2252962 TI - Treatment with marrow transplantation or immunosuppression of childhood acquired severe aplastic anemia: a report from the EBMT SAA Working Party. AB - A total of 304 children under the age of 15 years with acquired severe aplastic anemia (SAA) received immunosuppressive therapy (IS) (n = 133) or a matched bone marrow transplant (BMT) (n = 171). The projected 10-year survival is 48% and 63% respectively (p = 0.002). Results following BMT have improved considerably over the years from 49% in 1970-80, to 70% in 1981-83 (p = 0.002) and to 81% between 1984-88 (p = 0.08). Other favorable prognostic factors are the use of cyclosporin A (p = 0.004), no previous therapy (p = 0.006) and early BMT (p = 0.009). In multivariate analysis only the year of treatment proved significant (p = 0.02). In contrast, results of IS are greatly dependent on the severity of pre-treatment neutropenia with survival of 56% versus 37% for neutrophils more or less than 0.2 x 10(9)/l (p = 0.003). Poor survival was associated in univariate analysis with female sex (43%), post-hepatitis SAA (37%), children not receiving androgens (38%) and patients younger than 5 years (35%), especially if associated with a low neutrophil count (11%). In multivariate analysis only the degree of neutropenia proved significant (p = 0.005). These results suggest that IS is a satisfactory alternative therapy for children with moderately SAA in the absence of an HLA-identical sibling, although BMT remains the treatment of choice. In children under 5 years with very SAA, results with IS are so poor that a search for an unrelated matched donor is justified as early as possible. PMID- 2252963 TI - Disseminated Trichosporon capitatum infection in a patient with acute leukemia undergoing bone marrow transplantation. AB - A case of disseminated infection with Trichosporon capitatum is reported in a 23 year-old patient with acute myeloid leukemia undergoing HLA-mismatched bone marrow transplantation. He was receiving immunosuppressive therapy with cyclosporine and corticosteroids for acute graft-versus-host disease and he was severely neutropenic. While being treated with fluconazole for 28 days for an oropharyngeal candidiasis the patient developed a T. capitatum septicemia. He died despite receiving amphotericin B therapy. Autopsy revealed widespread infection with T. capitatum. The portal of entry was probably the digestive tract in this patient as T. capitatum had been first isolated in the stools. PMID- 2252964 TI - Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. AB - Eight cases of a persistent vegetative state caused by brain damage were treated by chronic deep-brain stimulation (stimulation target: the mesencephalic reticular formation and/or non-specific thalamic nucleus) over a period of more than 6 months. Three of the patients are currently able to communicate and to express their demands by voice and one other patient has recovered very close to this state. These four cases showed changeable spectrograms with desynchronization on continuous EEG recording and all components of the BSR and SER could be recorded except for prolonged latency of both N20 (SER) and the V wave (BSR) 2 months after the initial coma. Following chronic deep-brain stimulation, EEG and behavioural arousal responses were observed with increased r CBF, r-CMRO2 and r-CMRGL in the whole brain tissue. After 3-6 months of chronic deep brain stimulation, the prolonged coma scale rose in four of the eight cases and three cases emerged from the persistent vegetative state. Transmitter substances and their metabolites were also found to be increased in the CSF after chronic deep-brain stimulation. Based on these findings, chronic deep-brain stimulation represents a useful kind of treatment that can lead to emergence from a persistent vegetative state, if the candidate is selected by electrophysiological studies 2 months after the initial insult and if the stimulation is applied for more than 6-8 months using a high-safety chronic deep brain stimulating instrument. PMID- 2252965 TI - Prediction of outcome of prolonged coma caused by brain damage. AB - Thirty-one prolonged coma patients, who continued in a comatose state for at least 2 months, were classified electrophysiologically employing EEG, a compressed spectral array of continuous EEG frequency analysis, BSR, SEP and SSEP. The prognoses of long-term follow-up (at least 8 months) in these patients were compared with the results of such electrophysiological analysis and with the neurological gradings of the prolonged coma patients. In the continuous EEG frequency analysis, 22 cases were classified as having a changeable spectrogram, nine cases as having a slow monotonous spectrogram, and no cases as having a borderline spectrogram. We also classified the changeable spectrograms into the following three patterns: no desynchronization, slight desynchronization, and desynchronization. The nine cases with a slow monotonous spectrogram revealed severe damage of the brain stem and cerebral function with multimodality evoked potentials, and most of these cases could not survive without assisted respiration. The 22 cases with a changeable spectrogram had mild damage of the brain stem and cerebral function with multimodality evoked potentials, and these cases were identical with a persistent vegetative state. Three of the cases showed a changeable spectrogram that revealed a desynchronization pattern, normal BSR and normal N20 of SEP and SSEP, recovered spontaneously from the persistent vegetative state within 6 months after electrophysiological evaluation. We conclude that not only a neurological but also an electrophysiological classification is necessary to evaluate the brain function and prognosis of prolonged coma. PMID- 2252966 TI - Cognitive rehabilitation versus day treatment in head-injured adults: is there an impact on emotional and psychosocial adjustment? AB - Emotional and psychosocial adjustments are typically the most challenging problems faced by the head injured, but there exists a paucity in research as to how affective problems are best ameliorated. In the present analysis, emotional and psychosocial adjustment were evaluated as part of a study comparing the efficacy of cognitive remediation versus day treatment. Out of 24 head-injured patients, half were randomly assigned into either treatment condition, each conducted 4 days a week over an 8-week span. A more favourable outcome for emotional adjustment was postulated for the day-treatment programme, since it was far more nurturing compared with cognitive remediation, which was thought to be more challenging if not confronting. However, our differential hypothesis for the two treatments was not confirmed, because in both groups there was a lessening of depression as measured by the Katz Adjustment Scale. The need is discussed for providing ongoing structured activities for the head injured in order to facilitate their emotional and psychosocial adjustment. PMID- 2252967 TI - The relationship between neuropsychological function and brain damage detected by neuroimaging after closed head injury. AB - Studies relating neuropsychology and structural neuroimaging after closed head injury are reviewed. Particular attention is given to the question of the relative contribution of focal and diffuse damage to neuropsychological impairment. The evidence currently available emphasizes the importance of diffuse damage in closed head injury. Diffuse damage is not equally distributed in the brain, and the review suggests three axes that are relevant for neuropsychological function: (1) damage may be unilateral or bilateral, (2) damage is characteristically greater in anterior regions than posterior regions, and (3) damage shows a centripetal gradient. A large gap remains between the emergent generalizations concerning head injury and reliable neuropsychological interpretation of scans from individual patients. PMID- 2252968 TI - Hypertension in traumatic brain injury. AB - The incidence and natural history of hypertension associated with traumatic brain injury were studied using a cohort of 80 patients discharged from a brain-injury rehabilitation centre. Although a significant incidence (15%) of hypertension is documented in traumatic brain-injured patients, the problem appears transient for most patients. Nonetheless, hypertension after brain injury merits treatment while it is an ongoing process for the anticipated few patients in whom it might persist. PMID- 2252969 TI - The rehabilitation of adolescents with traumatic brain injury: outcome and follow up. AB - Outcome data from 17 brain-injured adolescents discharged from a rehabilitation centre during a 2-year period were analysed. The outcome measures were academic status and living environment. The descriptive variables were demographic, behavioural, psychological and neuropsychological data for each client. Before admission, 24% of the adolescents were living at home with their parents, 29% were in rehabilitation hospitals and 47% were in psychiatric settings. At discharge, 58% were living with their families, 23% were living in group homes, 12% were in supervised apartments and 5% were in an alternative rehabilitation centre. Academically, 53% were discharged into public schools, 23% were competitively employed and 23% attended special schools. Follow-up reports, dated 8-24 months post-discharge, found that 40% of the adolescents continued to live with their parents and 30% were in public schools. All of the adolescents were living and working or attending school in the community. Factors in the successful rehabilitation of brain-injured adolescents are discussed. PMID- 2252970 TI - Long-term multi-dimensional outcome following isolated traumatic brain injuries and traumatic brain injuries associated with multiple trauma. AB - We retrospectively investigated long-term, multi-dimensional quality-of-life outcomes in 68 male patients who suffered pure head injuries and 63 male head injured patients with associated multiple trauma. Results indicated that patients sustaining associated multiple trauma were significantly younger and more deeply comatose on admission. Trends were found to suggest that patients sustaining associated multiple trauma also remain in coma longer, and experience more difficulties in social interaction and overall psychosocial functioning, but less difficulties in mobility compared with pure-head-injured patients. These findings should be taken into account in the evaluation of results of treatment as well as in the planning and allocation of resources for head-injured patients. PMID- 2252971 TI - Modification of severe behaviour problems following herpes simplex encephalitis. AB - Violent and sexually disinhibited behaviour together with poor self-care developed in a 38-year-old teacher following herpes simplex encephalitis. These behaviours were sufficiently severe to make rehabilitation difficult and return to the community impossible. Initially, only violent behaviour was treated, both by medication and a behaviour programme, and sexual disinhibition subsequently by the latter. In order to implement the programme a special (psychiatric) nurse was required on a 24 h basis. The incidence of violent behaviour was reduced from up to 55 times per day to zero over a period of 2 months. Whether this was affected by medication or behaviour management, or by spontaneous recovery, is discussed. Sexual disinhibition was eliminated in supervised settings, but continued to occur if left unsupervised and this improvement resulted from behaviour management. Poor personal hygiene also improved markedly over the 6-month period. The goal of returning the patient home to live with her family was achieved and she remained there at follow-up. This intervention was carried out in a rehabilitation unit that does not specialize in the treatment of such cases; clearly this has implications for cost and quality of care. PMID- 2252972 TI - The role of and possibilities for physical conditioning programmes in the rehabilitation of traumatically brain-injured persons. AB - The development of rehabilitation programmes for traumatically brain-injured persons is a complex and multidisciplinary effort. One aspect of such programmes is the development of physical work capacity via exercise or physical conditioning. This paper reviews literature dealing with the physical work capacity following traumatic brain injury and its responses to training. The incorporation of physical activity into a specific rehabilitation programme is described and the possible roles of exercise in the rehabilitation programme are discussed. PMID- 2252973 TI - AIDS and the rheumatic diseases. PMID- 2252974 TI - Echo planar imaging of the human fetus in utero at 0.5 T. AB - The snap-shot capability of the echo-planar imaging technique is used to freeze motion effectively in human fetal studies in utero. These first results obtained at 0.5 T demonstrate diagnostic quality images without the need for averaging. Although averaging improves the image signal to noise ratio, it is shown that significant image blurring is produced even when only eight separate images are averaged over a period of a few seconds. Results are presented showing anatomical detail of the internal organs of the fetus. Some pathology is also demonstrated. These results were obtained using the modulus blipped echo-planar single-pulse technique (MBEST). Running at 10 frames/second, the modulus version of the fast low-angle excitation echo-planar technique (FLEET) is used to produce ungated fetal cardiac movies. PMID- 2252975 TI - Magnetic resonance imaging in idiopathic retroperitoneal fibrosis: measurement of T1 relaxation time. AB - Magnetic resonance imaging at 0.08 Tesla was performed in nine patients with proven idiopathic retroperitoneal fibrosis. A total of 11 scans was performed. Three patients were scanned before diagnosis; one of these also had two follow-up scans. A further six patients were scanned a variable time after diagnosis and treatment. On each scan, a periaortic soft-tissue mass was readily identified, the distribution corresponding to that seen on computed tomography. There was no difference in the mean T1 relaxation time of the mass between patients scanned before diagnosis and those scanned after treatment. However, the patient followed with serial scans showed a progressive reduction in the T1 value of the mass with time. Comparison with results obtained in patients with lymphoma suggests that the T1 values in retroperitoneal fibrosis are lower than in lymphoma, particularly non-Hodgkin's lymphoma. PMID- 2252976 TI - The relationship of "high risk" mammographic patterns to histological risk factors for development of cancer in the human breast. AB - In the UK Trial for the Early Detection of Breast Cancer in Nottingham, 119 women were identified as having fibrocystic change with epithelial hyperplasia or in situ carcinoma. Their mammograms were classified according to Wolfe's criteria and the corresponding histology for each patient was classified for degrees of epithelial hyperplasia, atypia and in situ neoplasia using Page's criteria. A control population of patients presenting for breast screening was used to represent the general population. No correlation was found between the four mammographic Wolfe patterns, N1, P1, P2 and DY and histological evidence of epithelial hyperplasia, atypia or in situ carcinoma. A further study was carried out to determine histological features of Wolfe pattern, using radiological examination of resected breast tissue. The variation in Wolfe pattern was related to the distribution of fibrous and adipose tissue in the breast interlobular stroma and appeared to have no relationship to epithelial parenchymal content. This information does not support the hypothesis that radiographic densities of P2 and DY patterns correspond to high risk epithelial proliferation. PMID- 2252977 TI - The role of indium-labelled leukocyte imaging in pyrexia of unknown origin. AB - Indium-111-labeled white blood cell scanning is often used in the investigation of pyrexia of unknown origin (PUO) to locate an otherwise occult source of sepsis. From a series of 166 white blood cell studies performed for sepsis, 28 cases of true PUO were identified and reviewed. The sensitivity was 60% and specificity 70%, with a positive predictive value of 38% and negative predictive value of 90%. Only 11% of studies revealed a pyogenic cause for PUO. These results are discussed and the potential role of gallium scanning in PUO is raised. PMID- 2252978 TI - Urinary tract dilatation in constipated children. AB - Abnormalities of the upper urinary tract were sought retrospectively in 180 children with constipation who had been investigated surgically over a 5-year period. Of those in whom an intravenous urogram had been performed, the incidence of dilatation of the upper renal tract was high, but only 12% of the patients with non-organic constipation had been so investigated. PMID- 2252979 TI - A clinical application of iodine quantitation using digital fluorography. AB - A preliminary clinical study of 20 patients is described in which a method of iodine quantitation in vitro using digital fluoroscopy was applied to the intravenous urogram. It was possible to quantitate iodine levels, in terms of mass thickness, in both the renal parenchyma and collecting system in 38 of 40 kidneys studied (20 patients). In the two kidneys on which measurements could not be made, the cause of failure was subtraction artefact due to movement of bowel gas, compounded in one case by poor renal opacification. The variations of iodine mass thickness against time were plotted and their forms were similar to dynamic computed tomography and magnetic resonance imaging studies of transplanted kidneys. Potential clinical applications of this method, in particular the functional assessment of the dilated upper urinary tract, are suggested based on its ability to offer quantitative information in addition to anatomical images. PMID- 2252980 TI - Lack of late skin necrosis in man after high-dose irradiation using small field sizes: experiences of grid therapy. AB - Out of a total of 437 patients with superior vena caval syndrome or advanced malignancy, given single-dose grid radiotherapy, four survived to 7 years. The dose to the skin under each of the 77 holes in the grid was approximately 58 Gy. The lack of skin necrosis in the total of 308 skin circles of 1 cm diameter among these survivors, compared with known necrosis rates in larger irradiated areas, implies that there is a marked field-size effect for late necrosis in small areas of irradiated skin. PMID- 2252981 TI - The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues. III. Effects on lung function. AB - The effect of single and fractionated doses of fast neutrons (42 MeVd----Be) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 +/- 0.94 for infinitely small X-ray doses per fraction. PMID- 2252982 TI - A survey of the radiation exposures received by the staff at two cardiac catheterization laboratories. PMID- 2252983 TI - Ultrasound cystography: a valuable technique. PMID- 2252984 TI - Skeletal abnormalities in a case of congenital erythropoietic porphyria. PMID- 2252985 TI - Computed tomography in volvulus of the midgut. PMID- 2252986 TI - The value of computed tomography in the diagnosis of atlanto-axial rotatory fixation. PMID- 2252987 TI - The nidus of an osteoid osteoma mimicking an os supratrochleare dorsale. PMID- 2252989 TI - A case of colonic defection. PMID- 2252988 TI - Radiological diagnosis and management of a solitary tuberculous hepatic abscess. PMID- 2252990 TI - High resolution, high field magnetic resonance imaging of joints: unexpected features in proton images of cartilage. PMID- 2252992 TI - Extrahepatic portal vein obstruction. PMID- 2252991 TI - Major contamination from an iodine-131 therapy patient. PMID- 2252993 TI - General surgical problems in pregnancy. PMID- 2252994 TI - Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy. AB - Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis. PMID- 2252995 TI - Preoperative cytology and mammography in patients with single-duct nipple discharge treated by surgery. AB - Microdochectomy has been the routine management for single-duct nipple discharge. Our review of 176 consecutive patients surgically treated between 1975 and 1988 revealed eight patients with in situ carcinomas and seven with infiltrative carcinomas. Seventeen patients had multiple papillomas, two had atypical hyperplasia and two had atypical epitheliosis. Case selection for surgery has recently been advocated. In our study, nipple discharge cytology was helpful in 67 per cent of cases with underlying malignant pathology. Mammography was found to be unreliable, alerting suspicion in only two of 15 cases. PMID- 2252996 TI - Microdochectomy for discharge from a single lactiferous duct. AB - Microdochectomy for persistent discharge from a single lactiferous duct was performed in 162 women. Invasive or in situ ductal carcinoma was diagnosed in 16 patients (10 per cent), none of whom had a palpable lump. The discharge was blood stained in 14 of these women and in two it was clear. Mammography was performed in 15 of these 16 patients and was abnormal in only five. Three patients had atypical ductal hyperplasia, one of whom subsequently developed an invasive ductal carcinoma. Microdochectomy for persistent discharge from a single lactiferous duct is curative and gives a diagnosis of the cause. It remains the treatment of choice whether the discharge is blood-stained or clear. PMID- 2252997 TI - Fine needle aspiration biopsy in the diagnosis and management of fibroadenoma of the breast. AB - Cytological and histological biopsies were obtained on 75 breast lumps clinically diagnosed as fibroadenomas. Of these, 95 per cent of lesions were benign. In 51 (68 per cent) confirmed as fibroadenomas histologically, cytology was benign in 78 per cent, but inadequate for diagnosis in 16 per cent. The remaining 24 lesions included three breast cancers and one lymph node with Hodgkin's disease. In this group cytology was inadequate for diagnosis in 54 per cent, including one breast cancer. No lesion with benign cytology was subsequently shown to be malignant. The study supports the view that clinical diagnosis and cytology are accurate in the diagnosis of benign breast disease of this type. Breast cancer may rarely present with the clinical features of a fibroadenoma and too few lesions have been studied to assess fully the performance of cytological biopsy in detecting these small mobile lesions. A non-excisional policy should therefore include prolonged follow-up and repeat biopsy. PMID- 2252998 TI - Microdochectomy: the precise identification of the suspicious duct. PMID- 2253000 TI - Development and reversibility of T lymphocyte dysfunction in experimental obstructive jaundice. AB - This study evaluates the effect of experimental biliary obstruction by bile duct ligation (BDL) and biliary drainage on cell-mediated immunity in Wistar rats. Immune status has been assessed by a mitogen stimulation test of T lymphocytes with phytohaemagglutinin. Animals were followed for up to 35 days after BDL. Regression analysis showed a significant negative correlation between lymphocyte function and the period of jaundice (correlation coefficient -0.57, P less than 0.001). Following BDL for 21 days, groups of animals had internal biliary drainage for 7, 14 and 28 days, and external drainage for 14 days. Compared with obstructed animals, 14 days internal drainage was required to improve lymphocyte function (P less than 0.05). Animals which had 14 days of external drainage had significantly lower lymphocyte stimulation than internal drainage animals (P less than 0.05). The results demonstrate that obstructive jaundice produces a progressive reduction of T lymphocyte function. This can be reversed by biliary drainage, internal drainage being more effective than external drainage. PMID- 2252999 TI - Reduced psychological morbidity after breast conservation. AB - Psychological morbidity was compared in 52 patients treated by mastectomy and 67 patients treated by lumpectomy for early breast cancer. An informal counselling service was provided for all patients. Morbidity was measured at 6, 9 and 12 months after surgery with two self-rating scales: the general health questionnaire and the Leeds depression and anxiety scales. There was a significant excess of severe depression in the mastectomy group. In contrast to the findings of previous research, this result suggests that breast conservation reduces psychological morbidity. PMID- 2253001 TI - Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning. AB - Biliary tract obstruction or anastomotic leakage are common problems following liver transplantation. In a sequential study, 31 patients with a liver transplant were investigated by 99mTc-IODIDA (IODIDA) scanning and T tube cholangiography (TTC) and the results were compared with clinical outcome. Seven patients had an extrahepatic biliary obstruction and one patient had a biliary leak. In the detection of biliary complications TTC and IODIDA scanning were similar in terms of sensitivity (63 per cent for both) but TTC had a better specificity (79 per cent versus 60 per cent) and accuracy (74 per cent versus 60 per cent) than IODIDA scanning. When liver function was taken into account, the diagnostic efficacy of both tests in patients with bilirubin levels of less than 200 mumol/l was similar. With levels greater than 200 mumol/l there was a greater number of false positive results with IODIDA scanning (12 per cent versus 54 per cent). The only significant biliary leak was clearly detected by TTC but not IODIDA scanning. TTC remains the more effective way of evaluating the biliary tract after transplantation. IODIDA scanning has limited value when bilirubin levels are elevated, but may provide additional information about blood supply, hepatocyte function and intrahepatic cholestasis. PMID- 2253002 TI - Regional chemotherapy for colorectal liver metastases: a phase II evaluation of targeted hepatic arterial 5-fluorouracil for colorectal liver metastases. AB - The results of systemic chemotherapy in patients with liver metastases from colorectal cancer remain dismal. Regional chemotherapy has been advocated as a method of improving the delivery of cytotoxic drugs to tumour, while minimizing systemic toxicity. The use of vasoactive agents to redistribute arterial blood flow towards tumour, and of biodegradable microspheres to slow tumour blood flow, have also been suggested as methods of further improving tumour exposure to drug. We present 21 patients who received intrahepatic arterial chemotherapy for colorectal liver metastases. Combined treatment (angiotensin II, albumin microspheres and 5-fluorouracil) was administered 4-6 weekly, and bolus 5 fluorouracil was given in the intervening weeks. Toxicity was minimal. Responses were seen in seven patients. Fewer than half of the deaths were from liver metastases; a quarter of the patients died from non-cancer-related causes. Survival was prolonged in the treated group compared with historical controls. These results suggest that this regimen has activity in patients with colorectal liver metastases. PMID- 2253003 TI - Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. AB - From 1960 to 1987, 1209 patients with colorectal liver metastases were recorded, and followed until 1 January 1990. In 242 cases the diagnosis was based on external imaging, whereas 967 patients had operative confirmation and staging of their liver disease. Three groups of patients were analysed: group 1 involved 921 cases, of whom 902 were deemed non-resectable whereas 19 could not be unequivocally classified. Only 21 patients lived for longer than 3 years, seven survived for 4 years, but there were no 5-year survivors. Group 2 comprised 62 highly selected patients who at laparotomy demonstrated resectable metastatic spread confined to the liver, but this was not treated mainly because of a formerly different therapeutic approach. These patients had a significantly longer median survival time (14.2 versus 6.9 months), but also failed to achieve 5-year survival. The 226 patients forming group 3 underwent hepatic resection with intent to cure. Nine of them had minimal macroscopic disease left, and 34 with all gross tumour removed had positive margins. Survival of patients with these 43 eventually non-radical resections followed an identical course as in group 2 (median survival 13.3 months, maximum 42 months). Of the 183 patients with potentially curative resection ten died after surgery (5.5 per cent). Actuarial 5 and 10-year survival rates in the remaining 173 patients were 40 and 27 per cent with 25 and seven patients alive at respective periods of time. Until 1 January 1990, 64 patients remained free from recurrent disease for up to 24 years. In three patients the tumour status at death was unclear. The other 106 patients developed definite cancer relapse. Nevertheless they demonstrated a prolongation of survival time by a median of 1 year when compared with the 43 non radically resected patients or the 62 untreated patients with resectable liver only metastases, and accomplished a maximum survival time of 8 years. Radical excision of colorectal secondaries to the liver therefore offers effective palliation, and in a small number the chance of a cure. PMID- 2253004 TI - Antigen CA 19-9 and mucinous cystadenoma of the pancreas. PMID- 2253005 TI - Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. AB - The APACHE II severity of disease classification system has been examined prospectively in 160 patients with acute pancreatitis. Using clinical and simple laboratory data APACHE II was able to provide useful discrimination between uncomplicated, complicated and fatal attacks within a few hours of admission. Peak APACHE II scores (recorded during the first 3 days) had a prognostic accuracy similar to the multiple factor scoring systems, but then incurred a similar delay. Patients could be graded according to their risk of death or of developing a major complication; no deaths occurred in patients with a peak APACHE II score less than 10. APACHE II can be repeated daily, uncomplicated attacks demonstrating falling scores in association with clinical improvement, in contrast to the rising scores associated with clinical deterioration in those dying early. APACHE II appears to reflect any continuing disease activity and may prove a useful means of monitoring the course of the illness and response to therapy. PMID- 2253006 TI - Gallstone clearance: a randomized study of extracorporeal shock wave lithotripsy and chemical dissolution. AB - Following extracorporeal shock wave lithotripsy it is not known whether gallstone fragments are cleared from the gallbladder without the use of oral dissolution therapy. To assess the efficacy of lithotripsy and dissolution therapy, alone or in combination, 35 patients were randomized to one of three treatment groups: lithotripsy alone, dissolution therapy alone or combined lithotripsy and dissolution therapy. All patients had symptomatic gallstones, functioning gallbladders and comparable stone profiles. Lithotripsy was administered using a piezoelectric lithotripter. Dissolution therapy consisted of combined bile acid and terpene. Clearance was assessed at 6 months using ultrasound and oral cholecystography. Patients with less than 50 per cent stone clearance at the end of 6 months were considered failures. The number of patients with total or partial clearance in the combined group (7/10) was significantly greater than those in the lithotripsy alone group (0/10, P less than 0.002). Gallstone clearance following lithotripsy appears to be dependent upon dissolution therapy. PMID- 2253007 TI - Gallbladder surgery following cholecystlithotripsy: suggested guidelines for treatment. AB - Twenty-three of 229 symptomatic patients undergoing cholecystlithotripsy underwent surgical intervention: 22 of the patients had cholecystectomy performed (five also undergoing choledochotomy) and one patient had a cholecystostomy. Of these 23 patients, five were lithotripsy failures, five developed acute pancreatitis, one had acute cholecystitis, and one had cholangitis. One patient had her gallbladder removed incidentally at the time of surgery for a bleeding gastric ulcer. Ten patients underwent surgery for recurrent biliary pain, probably related to fragment passage via the cystic duct. We suggest that up to 16 of these 23 patients did not necessarily require cholecystectomy, i.e. five patients with pancreatitis, one patient with cholangitis and ten patients with recurrent biliary colic. Conservative and/or endoscopic management may be successful in the first instance to allow further treatment with lithotripsy in the majority of patients. If, however, the expertise to perform endoscopic sphincterotomy is not available or the patient declines further lithotripsy, then resort to surgery may be necessary. We propose that it is the responsibility of the management team in charge of the lithotripsy unit to inform both the patient and the referring clinicians of the possible side-effects and outcome of treatment in an attempt to avoid unnecessary surgical procedures. PMID- 2253008 TI - Treatment of sleep apnoea by vertical gastroplasty. PMID- 2253009 TI - Surgical presentation of Kawasaki disease (mucocutaneous lymph node syndrome). AB - Five patients with Kawasaki disease (mucocutaneous lymph node syndrome) are reported whose varied presentations included acute abdominal pain, peripheral arterial aneurysms, digital gangrene and sterile pyuria and whose presenting pathology ranged from hydrops of the gallbladder to enteric pseudo-obstruction. As the complications of the disease can usually be managed without resort to surgery, which is associated with a mortality rate of up to 25 per cent, the recognition of Kawasaki disease will prevent hazardous and unnecessary laparotomy. PMID- 2253010 TI - Vastus lateralis myocutaneous flap for reconstruction of defects around the groin and pelvis. AB - We present our experience using the vastus lateralis myocutaneous flap for the repair of defects around the groin and pelvis. It is a relatively new technique, with many advantages over other flaps used in this area, though it has limitations. The history, anatomy and surgical technique of raising the flap are described and clinical cases are discussed. The importance of patient selection is highlighted. PMID- 2253011 TI - Massive gastrointestinal haemorrhage due to ileal varices. PMID- 2253012 TI - Association between extent of colonic mucosal sialomucin change and subsequent local recurrence after curative excision of primary colorectal cancer. AB - Two interrelated studies were carried out to determine whether extent of sialomucin change adjacent to a primary colorectal carcinoma predicted local tumour invasiveness and risk of local recurrence. In the first, depth of tumour penetration was correlated with the length of the sialomucin band adjacent to 72 primary colorectal cancers. There was a significant (P less than 0.05) increase in sialomucin band length adjacent to tumours invading adjacent structures compared with those which had not (Mann-Whitney U test), although there was no overall correlation between depth of penetration, Duke's classification or degree of differentiation (Kruskal-Wallis test). A sialomucin band of greater than 3 cm was associated with a 70 per cent probability of adjacent structure (T4) invasion. These observations were then tested prospectively in a second study involving 256 patients to determine whether the presence of a greater than 3 cm sialomucin band could predict local recurrence. Presence of a greater than 3 cm sialomucin band was a significant (x2 = 7.12, d.f. = 1, P less than 0.001) and independent predictor of local but not distant recurrence. In addition both the interval to local recurrence and survival were significantly shorter if a greater than 3 cm sialomucin band was present. However the accuracy of greater than 3 cm sialomucin band as a predictive test for local recurrence was only 70 per cent. The extent of sialomucin adjacent to a primary colorectal cancer does provide a crude assessment of tumour invasiveness and risk of local recurrence. PMID- 2253013 TI - Intraluminal pressure adjacent to left colonic anastomoses. AB - A cumulative total of 89 h of pressure data was acquired from both sides of a left colonic anastomosis in 15 patients over a median period of 7 postoperative study days. Patients had a colonic ileus lasting 3-10 days and during this proximal and distal inactivity the intraluminal pressure remained within 6 mmHg of atmospheric pressure. After recovery of activity, pressures proximal to the anastomosis in excess of 10 mmHg occurred during less than 1 per cent of the recording time. Distal peak pressures were significantly elevated with respect to the proximal site (P less than 0.001). Two-thirds of the distal pressures recorded were between 10 and 20 mmHg and 98 per cent were less than 50 mmHg; the peak distal pressure was 90 mmHg. Four patients had distal repetitive tonic contractions creating a pressure difference across the anastomosis with a mean of 20 mmHg and a peak of 45 mmHg. Each contraction persisted for 15-20 min. Intraluminal pressures are unlikely to play a role in anastomotic dehiscence. PMID- 2253014 TI - Effect of hydrocele on testis and spermatogenesis. AB - One hundred and twenty cases of big unilateral hydrocele of the tunica vaginalis testis have been studied to ascertain the effect on the structure and function of the testis, taking the normal side as control. There was no pressure effect from the hydrocele on the structure of the testis in 70 per cent, a flattening of testis in 22 per cent, and atrophy of testis in 8 per cent of cases. There was partial arrest of spermatogenesis in 10 per cent and total arrest of spermatogenesis in 8 per cent of cases. The remaining 82 per cent showed normal spermatogenesis. PMID- 2253015 TI - Buerger's colour. AB - Cyanosis of the hands and feet in Buerger's disease is known as 'Buerger's colour'. This characteristic skin colour is produced by the subpapillary venous plexus. The reactions of the subpapillary venous plexus in patients with Buerger's disease were observed by analysing the fractional blood volume of tissue using a visible light reflective spectrophotometer. Capillary morphology was investigated using an intravital video-microscopic system. Twenty-seven subjects, comprising 13 normals and 14 patients with Buerger's disease, were studied. In the nailbeds of patients with Buerger's disease, an increase in the number of loops, cyanotic colour change and dilatation were observed. In this condition there was incompetence of venular tonus and regurgitation at venular valves. Buerger's colour is probably due to excessive congestion of venous blood in the subpapillary venous plexus which is produced by these mechanisms. PMID- 2253016 TI - Thallous chloride uptake and DNA profile in parathyroid adenomas. AB - Thallium isotope scintigraphy is used to localize parathyroid adenomas but the mechanism underlying the technique is poorly understood. While larger adenomas are reliably localized the results are less certain for small tumours. This study explores the relationship between cellular DNA profile and thallium uptake (localization accuracy) in 24 parathyroid adenomas. The DNA profile was assessed using flow cytometry and standard subtraction thallium scintigraphy was performed before surgery. Fifteen of the 24 adenomas demonstrated excessive mitotic activity and 13 of these glands were accurately localized. Of the remaining nine glands, only five were localized accurately (P less than 0.01, chi 2 test including Yates' correction). This difference in thallium uptake could not be accounted for on the basis of gland weight. Thallium localization of parathyroid adenomas is related to mitotic activity. This may explain some of the limitations of this technique. PMID- 2253017 TI - Duodenogastric reflux and gastric histology after cholecystectomy with or without sphincteroplasty. AB - Sixteen patients who had undergone cholecystectomy plus sphincteroplasty, 14 cholecystectomized patients and ten control patients were studied to evaluate whether differences existed in duodenogastric reflux and whether these were related to morphological damage of the gastric mucosa. Duodenogastric bile reflux during fasting was evaluated by measuring the concentration of total bile acids (by an enzymatic method) and single bile acids in the gastric juice by high performance liquid chromatography. The damage was evaluated histologically by systematic endoscopic biopsy of the antrum and body of the stomach. There was a statistically significant difference in fasting bile reflux between the three groups (Kruskal-Wallis test, P less than 0.001), and the group that underwent cholecystectomy plus sphincteroplasty had a significantly higher median value than the cholecystectomized group (P less than 0.05) and the control group (P less than 0.01). The distribution of chronic antral atrophic and superficial gastritis was different in the three groups (chi 2 test, P less than 0.005). Chronic atrophic gastritis was associated with cholecystectomy plus sphincteroplasty (P less than 0.01), while chronic superficial gastritis was more frequent in cholecystectomized patients. These results suggest that there may be more duodenogastric reflux after cholecystectomy plus sphincteroplasty than after cholecystectomy alone, and that there may be a correlation between the amount of duodenogastric reflux and the severity of mucosal damage. PMID- 2253018 TI - Intragastric balloons for morbid obesity. PMID- 2253019 TI - Urine acid output after a test meal. PMID- 2253020 TI - Asymmetrical nature of the muscular anatomy of the infantile pylorus. PMID- 2253021 TI - Extrapleural intercostal analgesia after thoracotomy. PMID- 2253022 TI - Metabolic effects of cancer. PMID- 2253023 TI - Percutaneous endoscopic gastrostomy. PMID- 2253024 TI - Thromboprophylaxis--combination of graduated compression stockings and pharmacological substances. PMID- 2253025 TI - Sympathetic preganglionic neurones in neonatal rat spinal cord in vitro: electrophysiological characteristics and the effects of selective excitatory amino acid receptor agonists. AB - Intracellular recordings were made from 52 lateral horn neurones in thin slices of neonatal rat thoracolumbar spinal cord. Of these neurones 12 were spontaneously active and the remainder silent. A number of these cells could be activated antidromically by stimulation of ventral roots. The conduction velocity of the antidromic potential was estimated to be 0.9-2 m/s which is within the range reported for axons of sympathetic preganglionic neurones (SPNs). The membrane properties of antidromically identified SPNs were similar to other lateral horn neurones included in this study and comparable to those reported for SPNs by others. Spontaneous burst firing was recorded in 3 neurones and activity in a further 5 neurones was characterized by the discharge of an action potential followed by an afterhyperpolarization potential (AHP) of peak amplitude 3-13 mV and duration 0.5-4 s. The AHP had an initial fast component (fAHP) which was sensitive to the potassium channel blocker tetraethylammonium (TEA), and a second slower component (sAHP) which was both sensitive to extracellular calcium and TEA. The effects of the selective excitatory amino acid receptor agonists N methyl-D-aspartate (NMDA), kainate and quisqualate were investigated by superfusion of the agonists, at known concentrations (100 nM to 100 microM). These agonists induced concentration-dependent depolarizations which were primarily associated with a reduction in neuronal input resistance. NMDA-induced depolarizations were potentiated in the absence of magnesium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253026 TI - Plasticity of some spinal dorsal horn neurons as revealed by pentobarbital induced disinhibition. AB - Extracellular activity was recorded from single spinal dorsal horn neurons in physiologically intact, awake, drug-free cats before and after the intravenous administration of 20 mg/kg pentobarbital (Pb). Pb produced a series of changes in response properties that reflect a significant moment-to-moment plasticity of some spinal dorsal horn neurons. Pb administration unmasked the ability of some low-threshold (LT) neurons to respond to noxious mechanical or thermal stimuli resulting in their being reclassified as wide dynamic range (WDR) neurons. Pb also appeared to unmask an afterdischarge in some neurons following noxious mechanical stimulation. In addition, some neurons appeared to be better able to signal changes in the intensity of mechanical stimulation after Pb. Neuronal receptive fields for low threshold stimulation were reduced in many instances but enlargement was also observed. The responses of some neurons to peripheral stimulation were unchanged by Pb. We hypothesize that the relatively low doses of Pb used in the study reduced tonic inhibition of some spinal dorsal neurons although the observed effects could have been produced by excitation. PMID- 2253027 TI - The influence of daily electrical stimulation of the amygdala on optokinetic nystagmus in rabbits. AB - To clarify the role of the amygdala in optokinetic nystagmus (OKN), the following experiment was carried out. Electrical stimulation, using 0.1-ms, 200-Hz pulse waves of 100 microA over a 30-s period, was performed once daily for 10 days to the amygdala of rabbits (medial or lateral area). Daily electrical stimulation of the medial area of the amygdala caused a significant increase of OKN frequency in rabbits. PMID- 2253028 TI - The ontogeny of feline temporal lobe epilepsy: kindling a spontaneous seizure disorder in kittens. AB - We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals. Preadolescent kittens (n = 12 less than or equal to 6.5 months) are far more likely to develop epilepsy, indexed by spontaneous seizures, than are adult cats (n = 12 greater than 1 year). Moreover, youth accelerated the development of epilepsy. The younger the kitten at the beginning of kindling, the more probable and rapid the onset of spontaneous seizures. Failed postictal depression was the most reliable precursor of spontaneous seizures in immature cats. However, spontaneous epilepsy continued after postictal refractory periods stabilized and was still present when kittens matured to adulthood. Collectively, the results suggest that failed inhibition contributes to the onset of spontaneous epilepsy in immature animals but that other morphologic, physiological and/or chemical changes might sustain epilepsy afterwards. PMID- 2253029 TI - Differential acute influence of medial and lateral preoptic areas on sleep wakefulness in freely moving rats. AB - The role of preoptic area (POA) in sleep-wakefulness and related EEG changes is well established. Anatomically the area is divided into medial (mPOA) and lateral (IPOA) portions having different physiological functions. Knowledge regarding the differential role, if any, of those two areas in sleep and wakefulness was lacking in the literature. Therefore, an attempt was made in this study, to investigate the same systematically. Experiments were conducted during day and night in freely moving rats. Electrophysiological parameters defining sleep and wakefulness were recorded before and after reversible inactivation of those two areas separately by microinjection of a local anaesthetic, marcain. The responses were opposite in nature depending upon the time, day or night, when the anaesthetic was applied. During the day, anaesthetization induced wakefulness while during the night, sleep was precipitated. However, anaesthetization of both the areas though induced similar qualitative response, the degree of the responses differed significantly. The results suggest that the mPOA is more effective in maintaining tonic sleep while the IPOA is more potent in the maintenance of tonic wakefulness in the normal rats. The finding supports and fits well with the existing knowledge. PMID- 2253030 TI - Chronic estradiol treatment alters central cholinergic function in the female rat: effect on choline acetyltransferase activity, acetylcholine content, and nicotinic autoreceptor function. AB - The purpose of the present study was to determine the effects of chronic (2 month) estradiol (E2) treatment on cholinergic function in the frontal cortex, hippocampus and hypothalamus of the female rat. Chronic E2 treatment selectively increased choline acetyltransferase (ChAT) activity in the frontal cortex and decreased ChAT activity in the hypothalamus: hippocampal ChAT activity was not significantly changed. The decrease of ChAT activity in the hypothalamus was paralleled by a significant reduction in the content and release (basal and evoked) of acetylcholine (ACh) in this structure. Neither the content nor the release of ACh was altered in the frontal cortex. In the hippocampus, there was a significant increase in spontaneous ACh release; however, hippocampal ACh content and evoked ACh release were not changed. Chronic E2 treatment also altered nicotinic binding sites in these same regions as determined by saturation analysis of [3H]methylcarbamylcholine (MCC) to membranes. There was a decrease in the affinity and an increase in the density of [3H]MCC binding sites in hippocampal membranes and an increase in the density of [3H]MCC binding sites was observed in hypothalamic membranes. These alterations were paralleled by changes in nicotinic autoreceptor function within these two structures. In the hippocampus, the increase in spontaneous ACh release induced by MCC in control animals was no longer apparent after chronic treatment with E2. In hypothalamus, higher concentrations of the nicotinic agonist were required to increase spontaneous ACh release in slices from E2-treated rats as compared to control rats. Taken together, these results suggest that chronic E2 treatment decreases presynaptic cholinergic function in the female rat hippocampus and hypothalamus. PMID- 2253031 TI - A novel effect of MPTP: the selective suppression of paradoxical sleep in cats. AB - We studied the effect of MPTP on sleep-wakefulness cycle in cats. Five mg/kg n methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered i.p. for 5 consecutive days. Electrocorticographic, electrooculographic and electromyographic recordings were performed before (5 days), during (5 days) and after (14 days) the treatment. Total selective paradoxical sleep deprivation was observed from the first injection. This effect lasted 6-9 days after the last dose, while the relative amount of slow wave sleep increased. The Berg-Fourier analysis showed no significant change in the EEG power spectra of slow-wave sleep during the paradoxical sleep deprivation compared to control period. Recurrence of paradoxical sleep was parallel to the disappearance of the motor symptoms. Histopathological investigation showed neuronal loss mainly in the substantia nigra. Our present study suggests a complex behavioral effect of MPTP. PMID- 2253032 TI - Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone. AB - In order to determine whether pyramidal cells of the adult hippocampus are morphologically sensitive to thyroid hormone, we performed single-section Golgi impregnation analyses on brains from hyperthyroid and control rats. Quantitative analyses of Golgi-impregnated pyramidal cells from the CA1 region showed a significant decrease in the density of apical dendritic spines with hyperthyroidism. In contrast, no changes were observed in spine density of basal dendrites or in cross-sectional cell body area of CA1 pyramidal cells. No changes in any of these morphological variables were detected in pyramidal cells of the CA3 region with hyperthyroidism. These results suggest that spine density of the apical dendrites of CA1 pyramidal cells is specifically affected by thyroid hormone in adulthood. Since dendritic spines are thought to represent postsynaptic sites it is likely that this morphological change results in altered hippocampal function. PMID- 2253033 TI - The effect of systemic cocaine on the responses to noxious stimuli and spontaneous activity of medial bulboreticular projection neurons. AB - The effect of antinociceptive doses of cocaine (25 mg/kg, i.p.) on unit responses to noxious somatic stimuli and spontaneous activity of antidromically identified projection neurons in the medial medullary reticular formation (MRF) was studied in the rat. Thirty-three antidromically activated neurons were recorded from the medullary raphe, gigantocellular, or paragigantocellular nuclei in an acute anaesthetized preparation; 25 cells projected to the spinal cord and 8 neurons had rostral projections through the medial forebrain bundle (n = 4) or the medial thalamus (n = 4). After cocaine administration, 24 (73%) of these cells showed immediate (less than 5 min) and prolonged (45-70 min) increases in their level of spontaneous activity. Associated with this increased interstimulus activity, 21 of 29 (72%) neurons responsive to noxious somatic stimulation reduced their responsiveness, relative to prestimulus activity, after cocaine administration. In 5 animals tested, the cocaine-induced changes in spontaneous activity and changes in evoked responsiveness were unaffected by naloxone (1 mg/kg, i.p.) but partially reversed within 5 min of the administration of chlorpromazine (3 mg/kg, i.p.). There were no obvious differences in neuronal response characteristics or the effect of cocaine that correlated with anatomical location or direction of axonal projection. Similar results were obtained while recording from 14 somatically responsive units in chronic, unrestrained, lightly anesthetized or awake rats. These findings provide direct evidence that cocaine, in doses that are antinociceptive for the rat, affects both unit responses to noxious stimuli and the spontaneous activity of caudally and rostrally projecting bulboreticular neurons over a time course that parallels the behavioral antinociception. The observation that unit responses to somatic stimuli were reduced while spontaneous activity was unchanged or increased in most cells suggests that cocaine antinociception may be due to the activation of sensory inhibitory mechanisms mediated by the MRF. PMID- 2253034 TI - Inhibition by carbachol microinjections of presumptive cholinergic PGO-on neurons in freely moving cats. AB - The effects of microinjections of a cholinergic agonist, carbachol (0.2 micrograms/0.2 microliters), were examined on a population of presumptive cholinergic mesopontine PGO-on neurons that presents a tonic pattern of discharge during waking and exhibits short spike bursts preceding the onset of dorsal lateral geniculate PGO waves during paradoxical sleep and slow wave sleep just prior to it. PGO-on neurons were activated antidromically by the stimulation of the dorsal lateral geniculate, pulvinar and/or medial and intralaminar thalamic nuclei. They were all characterized by a long spike duration and a slow conduction velocity. Microinjections of carbachol near unit recording sites in freely moving cats induced a complete suppression of the spontaneous tonic activity during waking, but did not suppress the spontaneous phasic burst activity during sleep. Carbachol microinjections also resulted in a marked reduction in responsiveness of PGO-on neurons to orthodromic stimulation. These spike depressant effects lasted for approximately 90-120 min and were reversed completely by a local or systemic administration of atropine sulfate. These findings point to a direct inhibition of central cholinergic PGO-on neurons via a muscarinic autoreceptor and a difference in the mechanisms underlying the generation of tonic and phasic burst activity of PGO-on neurons occurring during waking and sleep. PMID- 2253035 TI - Dose-dependent effects of morphine differentiate self-administration elicited from lateral hypothalamus and mesencephalic central gray area in mice. AB - BALB/c mice were unilaterally implanted with a guide-cannula, the tip of which was positioned 1 mm above either the lateral hypothalamus (LH) or the mesencephalic central gray area (CG). On each experimental day, a stainless-steel injection cannula was inserted into the LH or the CG and self-administration of two doses of morphine (50 and 5 ng) was compared in the two brain structures using a spatial discrimination task in a Y-maze. At the dose of 50 ng, mice injected into the LH rapidly discriminated the reinforced arm from the neutral arm of the maze in order to self-administer morphine. In contrast, at this same dose, mice of the CG group do not show any regular self-administration behavior. At the dose of 5 ng, both LH and CG injected mice show a regular self administration response. The rate of discrimination was similar in the two groups. When naloxone (5 ng) was mixed with morphine (5 ng), the number of self administrations progressively decreased in both brain areas. This decrease was both larger and more rapid in CG than in LH. Marked signs of physical dependence (escapes from the maze) were observed in the two groups during this phase. Finally, when morphine alone (5 ng) was again made available, a regular self administration response reappeared in the two brain structures. These data suggest (1) that morphine has reinforcing effects in both LH and CG and (2) that in these two brain structures self-injection of this drug is dependent on an opiate receptor mediated mechanism. PMID- 2253036 TI - Nicotine interferes with GABA-mediated inhibitory processes in mouse hippocampus. AB - Previous studies indicated that the excitatory effects of nicotine may be mediated via interference with GABAergic transmission. Here, several variants of the paired-pulse paradigm were employed to ascertain whether nicotine interferes with endogenous inhibitory circuits in the hippocampus. Nicotine attenuated the inhibition evoked by antidromic (alvear) stimulation in the CA1 region in a concentration-dependent manner (EC50 = 60-75 microM). This same phenomenon was also observed for the GABAA receptor antagonist bicuculline (0.1 microM). Orthodromic-orthodromic paired-pulse paradigms were found to be unsuitable for investigating the effects of epileptogenic agents such as nicotine and bicuculline on endogenous inhibition. PMID- 2253037 TI - Ganglioside AGF2 promotes task-specific recovery and attenuates the cholinergic hypofunction induced by AF64A. AB - Ganglioside AGF2 attenuated both the cognitive impairments and the cholinergic hypofunction induced by ethylcholine aziridinium ion (AF64A). Adult male rats were initially trained to perform a standard radial arm maze (RAM) task. Following training, they were injected intraperitoneally with 10 mg/kg AGF2 (AF/AGF2, CSF/AGF2) or the saline vehicle (AF/SAL, CSF/SAL) for 3 days prior to and for 14 days following bilateral injection of AF64A (3 nmol/side) or artificial CSF into the lateral ventricles. AF64A (AF/SAL) impaired performance of the standard RAM task and a working memory version of the task in which various delays were imposed between the fourth and fifth arm choices. In contrast, animals that received AGF2 and AF64A (AF/AGF2) were initially impaired on the standard RAM task but rapidly recovered and were performing as well as the control groups (CSF/SAL, CSF/AGF2) by the end of training. The AF/AGF2 group, however, exhibited persistent deficits on the working memory version of the RAM task. These data demonstrate that AGF2 promotes behavioral recovery in a task dependent manner in this model system. Neurochemical analysis revealed that AF64A produced a significant 37% decrease in hippocampal ChAT activity that was significantly attenuated, but not prevented, by prior treatment with AGF2. Thus the behavioral recovery afforded by AGF2 might be related to increased cholinergic activity in the hippocampus that is sufficient for the performance of tasks which either lack or have a minimal working memory component. An analysis of the temporal profile of AGF2-induced neurochemical recovery revealed that ChAT activity was enhanced at 20, but not 2 or 11, weeks following AF64A. Since AGF2 did not attenuate the cholinergic cell loss (35%) induced by AF64A in the medial septum these data indicate that AGF2 might have (1) enhanced sprouting of cholinergic terminals following the initial insult, (2) directly increased ChAT activity in surviving neurons, or (3) induced behavioral and neurochemical recovery through a combination of these or other mechanisms. PMID- 2253038 TI - Ultrastructural immunolocalization of adenosine deaminase in histaminergic neurons of the tuberomammillary nucleus of rat. AB - Neurons in the tuberomammillary nucleus (TM) of the rat hypothalamus were immunolabelled for the enzyme adenosine deaminase (ADA) and investigated by electron microscopic immunohistochemical techniques. ADA-immunoreactivity was distributed throughout the somal and dendritic cytoplasm of TM neurons and in the karyoplasm of most, but not all of these neurons. Immunoreactive axons were rarely observed within the tightly packed cell clusters of the TM subdivisions examined. Dense deposition of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreaction product together with reasonable preservation of morphological detail facilitated identification of immunoreactive profiles and allowed characterization of the ultrastructural features of labelled neurons and the relationships of these with each other and with surrounding unlabelled neuronal and glial elements. Immunolocalization of ADA therefore represents a reliable and convenient method for the identification of TM neurons in EM studies of their ultrastructure and synaptic interactions. PMID- 2253039 TI - Interaction between raphe dorsalis and nucleus basalis magnocellularis in spatial learning. AB - We compared the effects on spatial learning of an ibotenic acid lesion of the nucleus basalis magnocellularis (NBM), a 5, 7-dihydroxytryptamine lesion of the raphe dorsalis (RD) and a combined NBM and RD lesion. The RD lesion reduced serotonin levels, and the NBM lesion reduced cholineacetyltransferase (ChAT) activity in the cortex. Although RD lesions alone did not affect spatial learning in the water-maze, the lesion aggravated the spatial navigation deficit produced by NMB lesioning. The current results suggest a functional interaction between the RD and NBM in spatial navigation. PMID- 2253040 TI - Noradrenaline induced stimulation of oxidative metabolism in astrocytes but not in neurons in primary cultures. AB - Noradrenaline effects on oxidative metabolism (tricarboxylic acid cycle activity) were examined by measuring the formation of 14CO2 from labeled aspartate in primary cultures of cerebral astrocytes and neurons and of cerebellar granule cells. At all time periods studied, CO2 formation in astrocytes was significantly increased in the presence of noradrenaline. The EC50 value was calculated to be 5 x 10(-7) M. No corresponding stimulation of CO2 production in cerebellar or cortical neurons was observed, suggesting that the stimulation of energy metabolism by noradrenaline in vivo may be confined to astrocytes. PMID- 2253042 TI - [Pharmacokinetic modeling in clinical practice: pefloxacin]. AB - Pharmacokinetic modelling allows to set up a therapeutic plan for administering a drug. The advances of this procedure are particularly remarkable in drugs discharged by the liver. The principles of this approach are presented and illustrated on the treatment with pefloxacin. The potential causes of the adverse effect of the drug observed in one patient of the series studied could thus be suggested. PMID- 2253041 TI - Effects of noise on high-affinity choline uptake in the frontal cortex and hippocampus of the rat are blocked by intracerebroventricular injection of corticotropin-releasing factor antagonist. AB - Acute exposure (20 min) to loud noise (100 dB) decreased sodium-dependent high affinity choline uptake activities in the frontal cortex and hippocampus of the rat. These effects were blocked by intracerebroventricular (i.c.v.) administration of the corticotropin-releasing factor (CRF) antagonist alpha helical-CRF9-41 (alpha-HCRF) immediately before noise exposure. Intracerebroventricular injection of CRF (1 microgram) also decreased high affinity choline uptake in the frontal cortex and the hippocampus of the rat, and these effects of CRF could be blocked by pretreating the animal with the narcotic antagonist naltrexone (1 mg/kg, i.p.). These results indicate that the effects of noise on central cholinergic systems are mediated by CRF and suggest a stressor CRF-endogenous opioid-acetylcholine sequence of effects in the brain. PMID- 2253043 TI - [Photodynamic therapy of human tumor xenotransplants in athymic nu/nu mice]. AB - The effect of phototherapy on the growth of two human tumors, i.e. carcinoma of the rectum I and III, was studied. The tumors were xenotransplated into athymic nu/nu mice. Meso-tetra-(para-sulfophenyl)-porphin, TPPS4, was used as photosensitizer. Incorporation studies showed the optimal dose for phototherapy to be 10 mg/kg TPPS4 and the time interval 72 hours. Under these experimental conditions (helium-neon laser, 632, 8, 300 J/cm2) one of six tumors was cured in the group with carcinoma of the rectum I, and that both after IV and IT administration of the photosensitizer. The other five experimental animals exhibited only partial responses to phototherapy. In the group with carcinoma of the rectum III, five out of six tumors were cured by IT administration of TPPS4 under the same experimental conditions. In one mouse there was only partial response to phototherapy. After IV administration of TPPS4, however, not a single tumor was cured and the response to phototherapy was only partial in all the six experimental animals. PMID- 2253044 TI - [Familial occurrence of Hodgkin's disease]. AB - Of a series of 300 patients with histologically verified Hodgkin's lymphoma, six cases of familial occurrence of the disease involving three families were reported from two clinical centers. In two families the affected patients were next of kin (daughter and father in the first family and two brothers in the third one). The interval between the onset of the disease was 6 years in the first and 4 months in the third family. In the second family an aunt and her niece were affected with an 18 year interval in the onset of the disease. The histological type was identical within the families involved (1 x LP and 2 x NS). Deficiency of cellular immunity was established in all the members of the two Prague families and the expression of HLA-A and B antigens of the MHC was determined in the first family. The involvement of environmental and genetic factors in familial Hodgkin's disease was analyzed also in the light of findings reported in the literature. PMID- 2253046 TI - [Trichomonas in girls during the period of hormonal inactivity]. AB - Trichomoniasis occurs also in childhood in the period of hormonal inactivity, though its rate is not so high as in women of childbearing age and full sexual activity. In our series of children in the period of sexual inactivity, established by functional cytology, trichomoniasis was diagnosed in 3.8% of the total number of 1,562 children. Preparations of imidazol proved to be fully effective in the treatment of trichomoniasis in girls. In diagnosis the semisolid Szenes's culture medium in Valent's modification was used to advantage. Its standard use provides a basic precondition for good recovery of the protozoon. Trichomoniasis as such does not present so serious a problem as do the consequences of the unrecognized and untreated disease when the proliferated secondary flora potentiates the severity of the infection. This condition may lead to salpingitis and peritonitis causing sterility, and it may also spread into the uropoietic system. PMID- 2253045 TI - [Splenectomy in hairy cell leukemia]. AB - Splenectomy was performed in five patients with hairy cell leukemia at the Surgical Department of the Hospital with Policlinic, Bezrucova, Bratislava, over the years 1982-1987. One of the patients died 3 years after operation due to progression of the disease, the other four patients have been surviving for 2-7 years following surgery without relapse of the disease. The presented results, compared with the world literature, justify splenectomy to be advocated as the primary therapeutic procedure in hairy cell leukemia. PMID- 2253047 TI - [Comparison of ultrasonic and computer tomography examinations of the intracranial space in early childhood]. AB - Comparison of ultrasound (US) and computer tomography (CT) examinations of intracranial pathology in early childhood yielded results speaking in favor of CT examination both in the light of overall precision and completeness of the information provided. The distress involved in the examination of generally seriously threatened children (anesthesia, radiation, transport) on the other hand, advocates US examination as the method of choice, particularly due to its noninvasiveness, the possibility to follow up the dynamics of the process in a series of examinations, its cost effectivity, mobility, threedimensional imaging ability, as well as the possibility to assess conditions that can be affected by treatment in early childhood. PMID- 2253048 TI - [Use of modern brain imaging methods in psychiatry]. AB - The paper expands on three methods of brain imaging developed over the recent years. Their physical principles are presented and their value in psychiatric research is discussed. PMID- 2253049 TI - [Chronology of scheduling repeated dives and its importance in professional diving]. AB - Repeated dives are frequently performed in diving practice. The value of proper chronology of sequencing repeated dives into different depths was verified by analyzing three professional tabular decompression systems. Sequencing of dives from greater to smaller depths proved to be the only correct algorithm. Such an algorithm plays an important role in preventing the development of critical supersaturation with inert gas and of potential manifestations of decompression sickness in divers. PMID- 2253050 TI - Art in the service of public health: the illustrated poster. PMID- 2253051 TI - The poster collection at the National Library of Medicine. PMID- 2253052 TI - Evolution of federal dietary guidance policy: from food adequacy to chronic disease prevention. PMID- 2253054 TI - Establishment of two new multi-drug resistant variants of the human tumor line Hep-2. AB - Two multi-drug resistant variants of the human carcinoma line Hep-2 have been selected by adaptation to progressively increasing concentrations of adriamycin. In comparison to the wild-type Hep-2 cells, the variant lines both showed approximately 100-fold resistance to adriamycin, 10 to 20-fold resistance to the vinca alkaloids but only 2-3 fold resistance to VP-16 and VM-26. There was essentially no difference between wild-type and variant cells in regard to sensitivity to threosulfan and 5-fluorouracil. The drug-resistant phenotype is stable for at least 3 months in the absence of drug, and is partially reversible by concomitant treatment with Verapamil. Chromosomal abnormalities consistent with gene amplification were observed in one of the variant lines. Sensitivity of variant cells to adriamycin was enhanced following trypsin-EDTA treatment. PMID- 2253053 TI - A comparison of the inhibition of deacetylase in primary cultures of rat and human hepatocytes effecting metabolism and DNA-binding of 2-acetylaminofluorene. AB - The metabolism of 2-acetylaminofluorene (AAF) in primary cultures of rat and human hepatocytes was investigated to determine if the activation of this well studied chemical carcinogen proceeds via similar routes of metabolism between species. The total level of AAF metabolite(s) bound to hepatocellular DNA was determined in the presence of deacetylase inhibitors, diethyl(p-nitrophenyl) phosphate (paraoxon) or bis(p-nitrophenyl) phosphate (BPNPP). These compounds are known to inhibit deacetylase and to decrease the mutagenicity of AAF. Experiments with rat and human hepatocytes demonstrated inhibition in the deacetylation of AAF (5 x 10(-4) M) with paraoxon or BPNPP. The BPNPP (5 x 10(-4) M inhibited 99% of the AF formation in the human hepatocytes and 88% inhibition in the rat hepatocytes. Paraoxon at 10(-4) M demonstrated a 98% inhibition of deacetylation with humans and a 92% inhibition with rats. The rat hepatocytes also showed a 53% decrease in DNA binding in the presence of paraoxon. In contrast with human hepatocytes, while paraoxon decreased the AF metabolite by greater than 97%, there was no change in total DNA binding. PMID- 2253056 TI - Widespread apathy and the public's reaction to information concerning the health effects of indoor air radon concentrations. PMID- 2253055 TI - Vanadium compounds promote the induction of morphological transformation of hamster embryo cells with no effect on gap junctional cell communication. AB - Vanadium compounds were found to promote the induction of morphological transformation of hamster embryo cells. Exposure of the cells to Na-O-vanadate, vanadin (V) oxide or vanadin (IV) oxide sulfate following pre-exposure to a low concentration of benzo[a]pyrene, potentiated the induction of transformed colonies similar to 12-O-tetradecanoylphorbol-13-acetate. Unlike this phorbol ester, vanadium compounds did not inhibit intercellular communication, or active protein kinase C. Nor did vanadate influence the reoccurrence of communication after removal of a communication blocking phorbol ester. On the other hand, vanadate showed strong synergism with the phorbol ester on induction of transformed morphology in the phorbol ester sensitive cell line BPNi. This suggests that vanadium and tumor promoting phorbol esters mediate their effect on the induction of morphological transformation of hamster embryo cells through different mechanisms. PMID- 2253057 TI - [Anesthesia and pollution]. PMID- 2253058 TI - [Massive surgery in pediatric orthopedics without homologous transfusion]. PMID- 2253059 TI - [The effect of the preanesthetic interview on anxiety prior to minor interventions]. PMID- 2253060 TI - [Anesthesia using propofol during surgery of strabismus in children. A comparison of two different protocols of induction and maintenance]. AB - The purpose of this study is an investigation of two protocols using propofol as induction and maintenance agent in 100 children scheduled for strabismus surgery (4-8 year, ASA I, NYHA I). Protocol I; Propofol 6 mg.kg-1 in 60 s with fentanyl 2 micrograms.kg-1 and vecuronium bromide 0.08 mg.kg-1 for induction, followed by propofol 11 mg.kg-1 for maintenance; Protocol II; Propofol 3 mg.kg-1 in 20 s with fentanyl 3 micrograms.kg-1 for induction, followed by propofol 12 mg.kg-1.h-1 for maintenance. It appears that the use of protocol I offers significant advantages compared with protocol II: a better quality of induction with a lesser incidence of pain during injection of propofol; a better quality of maintenance with very infrequent bradycardia from oculocardiac reflectivity; and a better recovery with a greatly reduced frequency of nausea and vomiting. PMID- 2253061 TI - [Criteria of recovery from caudal anesthesia in children]. AB - The authors evaluated the return of sensory, motor, and sympathetic nervous system function following caudal block in children. Twenty children, ASA PS I, aged 5 +/- 4 yr (mean +/- SD), weighing 22 +/- 9 kg, scheduled for lower abdominal and urologic surgical procedures were studied. Anaesthesia was induced and maintained by halothane, N2O and oxygen. A caudal block was performed with 1 ml/kg of 0.25% bupivacaine. Analgesia assessed by Broadman's score was efficient in 18 out of the 20 children during the first 4 hours after the block. Upper level of cutaneous analgesia was T10 +/- 2 after the block. Two hours after the caudal injection an incomplete motor blockade was found in 14 of 20 children, and at 4 hours no block was found in any child. Heart rate was significantly increased in the upright position (122 +/- 12 to 131 +/- 26 bpm at 2 hours, and 110 +/- 21 to 118 +/- 28 bpm at 4 hours), whereas arterial blood pressure was unchanged in the upright position. PMID- 2253062 TI - [Anesthesia in pediatric ophthalmology]. PMID- 2253063 TI - [Pulse oximetry: incidents in newborn infants]. PMID- 2253064 TI - [Ketamine infusion in tympanoplasty]. AB - The reduction of capillary hemorrhage obtained with ketamine induced us to use this agent in anaesthesia for eardrum plastic surgery. During a period of 8 years 278 operations of this type were performed with this method. Its results were very satisfactory especially with regard to postoperative analgesia. No increase of capillary bleeding was observed after a temporary rise of arterial pressure following induction. Premedication consisted of atropine 0.5 mg intravenous and diazepam (later substituted by midazolam) according to age and weight. Induction was realized with fentanyl 0.1 mg intravenously followed by ketamine 3 mg.kg-1 intravenously. Anaesthesia was maintained by infusion of ketamine (500 mg in 500 ml of saline solution), nitrous oxide-oxygen (50% each) inhalation and pancuronium or vecuronium. Ketamine infusion was stopped approximately 45 min before operation was completed. Most patients regained consciousness in about 15 to 30 min after nitrous oxide was discontinued. Side effects such as bad dreams were noticed only in 29 patients (10.43%). Perturbed recovery from ketamine anaesthesia might be largely prevented by psychological preoperative preparation and adequate dosage of the benzodiazepine used for premedication. PMID- 2253065 TI - [Peroperative septic shock during a percutaneous nephrolithotomy]. PMID- 2253066 TI - [Persistent left superior vena cava and catheterization of the pulmonary artery]. PMID- 2253067 TI - [An exceptional cause of pulmonary embolism]. PMID- 2253068 TI - [Rupture of the splenic pedicle during labor]. PMID- 2253069 TI - [Etomidate for cesarean section]. PMID- 2253070 TI - [The role of the anesthetist in the care of burn patients]. PMID- 2253071 TI - [Ambulatory surgery and anesthesia]. PMID- 2253072 TI - [Anesthesia of the burned child]. PMID- 2253073 TI - [Nalbuphine by the rectal route in children]. PMID- 2253074 TI - Side-chain specific beta-lactam allergy. PMID- 2253075 TI - Does inhaled PAF cause airway hyperresponsiveness in humans? PMID- 2253076 TI - Mediators of bronchial hyperresponsiveness. PMID- 2253077 TI - Pathogenesis of eczema. PMID- 2253078 TI - Macrophage-granulocyte interactions in allergic diseases. PMID- 2253079 TI - Allergy to penicillin with good tolerance to other penicillins; study of the incidence in subjects allergic to beta-lactams. AB - Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests. 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxy-methyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21.8% for skin testing with BPO-PLL, 9.3% with MDM and 12.5% with AX. Nine point three per cent were RAST positive to BPO and 1.5% to AX; 7.8% developed a positive response after challenge to BP, 7.8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6.9% of the total group would have been missed in this study using benzyl or phenoxymethyl penicillin diagnostic reagents alone. PMID- 2253080 TI - Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis. AB - In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1 year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults. PMID- 2253081 TI - Crossreactivity of IgE antibodies from sera of subjects allergic to both ryegrass pollen and wheat endosperm proteins: evidence for common allergenic determinants. AB - Positive RAST (greater than 5% radioactive uptakes) to wheat endosperm proteins were found in approximately one-quarter of subjects who had both a positive skin prick and RAST (greater than 10% radioactive uptake) to ryegrass pollen proteins. Immunoblotting of proteins electrophoretically transferred to nitrocellulose membrane after SDS-PAGE of ryegrass pollen and wheat endosperm proteins confirmed the crossreactive properties of the sera identified by RAST testing. Immunoadsorption of serum IgE onto nitrocellulose membrane, to which ryegrass pollen or wheat endosperm proteins had been adsorbed, removed IgE from crossreactive sera reactive to both ryegrass pollen and wheat endosperm proteins. Elution of the adsorbed IgE from the nitrocellulose membrane after immunoadsorption and probing blotted strips of both ryegrass pollen and wheat endosperm proteins supported the results obtained from the immunoadsorption experiments. This data provides evidence that the crossreactivity of IgE antibodies in sera reacting with both ryegrass pollen and wheat endosperm proteins involves common or related determinants and has implications for the clinical management of these allergic subjects. PMID- 2253082 TI - Role of insects as inhalant allergens in bronchial asthma with special reference to the clinical characteristics of patients. AB - The whole body extracts (WBEs) of 13 common insects from Delhi, namely Musca domestica (house fly); Sitophilus oryzae (rice weevil); Callosobrochous maculatus (pulse beetle); Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti (mosquitoes); Blattella germanica and Periplaneta americana (cockroaches: male, female and nymph); Spodoptera litura and Heliothis armigera (moths), were prepared to evaluate their allergenic significance in patients with allergic bronchial asthma. Intradermal (ID) tests were performed with these WBEs on 75 patients with bronchial asthma and 20 healthy non-allergic volunteers. An ID test was considered positive when the weal diameter was more than twice that of phosphate-buffered saline control and at least 6 mm in size and an erythema of more than 15 mm. In the patients 27.7% of the ID tests performed were total positive (1+ to 4+) as compared to 7.1% in the controls. Ten point two per cent of ID responses were markedly positive in asthmatics (2+ to 4+) as against none in controls. Of the 13 bronchial provocation tests (BPTs) performed on patients giving positive cutaneous responses, eight (61.5%) were positive. Similarly, RASTs were positive in 87.5% of the limited sera tested from the patients with positive ID responses. The patients with a positive family history of allergic disorders gave higher percentages of positive ID responses as compared to the asthmatics with no family history. Similarly, the ID positivity was significantly higher in patients with associated allergic diseases like allergic rhinitis as compared to the patients with bronchial asthma alone. Interestingly, we observed significantly higher ID response to insects in seasonal asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253083 TI - Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man. AB - The reproducibility of acute effects of inhaled PAF on airway calibre, circulating neutrophil count and any subsequent increase in bronchial responsiveness has been studied in six normal subjects and compared to the effects of inhaled lyso-PAF, the inactive precursor and metabolite of PAF. PAF caused acute bronchoconstriction and a transient fall in neutrophil count on two separate occasions in five out of six subjects (minimum percentage of baseline values (mean): first PAF challenge; sGaw 69%, Vmax30 72%; neutrophil count 70%; second PAF challenge; sGaw 61%, Vmax30 74%, neutrophil count 63%). In one subject inhaled PAF caused bronchoconstriction and a transient fall in neutrophil count once, but a second challenge resulted in no detectable changes. There was no significant increase in bronchial responsiveness to methacholine in any subject studied on five occasions over a 2-week period following each PAF challenge. Challenge with lyso-PAF did not cause acute effects or any subsequent changes in bronchial responsiveness. These findings demonstrate that any effects of inhaled PAF on bronchial responsiveness in normal man are small and probably not of clinical significance. It would also be inappropriate to use this human model to study the mechanisms of bronchial hyperresponsiveness or for the preliminary assessment of potential new anti-asthma drugs. PMID- 2253084 TI - Evaluation of Basidiomycete and Deuteromycete (Fungi Imperfecti) extracts for shared allergenic determinants. AB - Aqueous extracts of select members of the Basidiomycetes and Deuteromycetes (Fungi Imperfecti) were evaluated for the presence of shared allergenic determinants using skin prick and radio-allergosorbent test (RAST) inhibition. Twenty adults with perennial symptoms of rhinitis, with or without asthma, were skin-prick tested with six species of Deuteromycetes and seven species of Basidomycetes. Positive weal-and-flare reactivity to Pleurotus ostreatus was associated with Alternaria alternata, Fusarium solani and Epicoccum purpurescens. Positive skin reactivity to Calvatia cyathiformis was also associated with A. alternata and F. solani. Coprinus quadrifidus was associated only with F. solani, and Psilocybe cubensis was only associated with Aspergillus fumigatus. No other skin test associations were demonstrated. For every allergen tested by RAST inhibition, significant dose-dependent homologous inhibition was demonstrated. Although the ability of an individual heterologous extract to inhibit the direct RAST varied, inhibition was generally minimal. In the most extreme example, no heterologous allergen inhibited the A. alternata RAST. However, the Armillaria tabescens RAST was inhibited 52.6%, 38.1% and 25.1% by A. fumigatus, E. purpurescens, and Penicillium notatum, respectively, suggesting significant cross reactivity. These results suggest that, although shared allergenic determinants exist between select species of Basidiomycetes and Deuteromycetes, crossreactivity is minimal and its clinical significance is not clear. These data confirm that for reliable diagnosis of fungal allergy, representatives of both major groups must be used. PMID- 2253085 TI - Changes in non-specific nasal reactivity and eosinophil influx and activation after allergen challenge. AB - It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0.051 ml +/- 0.012 (mean +/- s.e.m.) to 0.255 +/- 0.062 (P less than 0.01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253087 TI - Immediate hypersensitivity to Parthenium hysterophorus. I. Association of HLA antigens and Parthenium rhinitis. AB - Lymphocytes collected from rhinitis subjects with strong positive skin reactions to the pollen allergens of Parthenium hysterophorus (American feverfew) having moderate to high titres of Parthenium-specific serum IgE were analysed for association of HLA-antigens covering 13 specificities of HLA-A, 17 specificities of HLA-B and eight specificities of HLA-DR loci by the NIH two-stage microlymphocytotoxicity assay. Comparison of the phenotypic frequencies of HLA-A and B antigens between Parthenium rhinitis subjects (n = 22) and control subjects (n = 137) did not suggest any significant association when tested for these antigen specificities. A significant correlation in the association of HLA-DR3 antigen with a relative risk of 11.33, however, was observed in Parthenium rhinitis subjects (n = 30) when compared to controls (n = 50). PMID- 2253086 TI - IgE, IgA and IgG antibodies and delayed skin response towards Candida albicans antigens in atopics with and without saprophytic growth. AB - Immunoblotting and RAST were used to analyse IgE, IgA and IgG responses to antigens of Candida albicans. These were compared with the delayed skin response and C. albicans carriage in 40 atopic subjects. The majority of the atopic patients showed a strong IgG and IgA antibody response towards mannan, a carbohydrate, but only occasionally to proteins. Altogether 22 of the 40 patients showed specific IgE towards C. albicans by immunoblotting. The IgE response was mainly towards proteins, particularly to ones with molecular weights of 29 kD and 46 kD, and only in eight out of 22 IgE-positive subjects towards mannan. The IgG and IgA responses to mannan and the total IgE response towards C. albicans assessed by RAST showed an association with C. albicans carriage, whereas the delayed skin response showed an inverse relationship. The immunological parameters characteristic of C. albicans carriage were found to be C. albicans specific depressed delayed skin response and elevated IgE, IgA and IgG responses. This situation in the atopics presenting such parameters may favour simultaneous sensitization and exposure by colonization. The degree of sensitization may be sufficiently high to produce symptomatic allergy, such as asthma, in some individuals during occasional overgrowth of C. albicans, e.g. due to antibiotic therapy. PMID- 2253088 TI - House dust mite allergen levels and an anti-mite mattress spray (natamycin) in the treatment of childhood asthma. AB - Natamycin, a fungicide marketed as Tymasil, is claimed to reduce house dust mite numbers and would therefore be expected to improve asthma in children with mite sensitivity. We have tested this assertion by a double-blind, placebo-controlled trial. There was no significant effect on levels of Der p I in mattress dust between active and placebo groups at the end of the spraying period. Histamine inhalation challenge PC20, clinic visit symptom scores and lung function tests reflecting either large or small airways obstruction were also unchanged. Therefore this product is not a therapeutic option for mite-allergic patients using the manufacturer's recommended dose and method of administration. Other factors influencing the Der p I levels were also investigated. Of these, only month of measurement and bedroom wall humidity showed any association. PMID- 2253089 TI - Hymenoptera venom anaphylaxis: may decreased levels of angiotensin peptides play a role? PMID- 2253090 TI - Ragweed IgE and IgG4 antibody in nasal secretions during immunotherapy. AB - We have developed sensitive amplified immunoassays for measurement of IgE and IgG4 ragweed (RW) antibodies in unconcentrated nasal washes. IgE to Amb a I (formerly antigen E) can be assayed to less than 0.1 ng/ml using IgE capture by anti-IgE on microtitre plates and an alkaline phosphatase-conjugated Amb a I with an amplification substrate technique. IgG4 to whole RW extract was assayed to less than 0.01 ng/ml by amplification ELISA using monoclonal anti-IgG4. Nasal washes (NW) (10 ml) and serum were obtained in December from 22 RW-sensitive patients before and after 1 and 2 yr of RW immunotherapy (IT), and assayed for Amb a I IgE or RW IgE and RW IgG4 antibodies Amb a I IgE could be measured in the NW of 15/22 pre IT, 19/22 at 1 yr IT, but only 3/10 at 2 yr IT (compared with pre IT, P less than 0.05). Mean Amb a I IgE in NW was 0.66, 0.36 and 0.21 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Mean serum RW IgE, was 76, 55 and 27 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Amb a I IgE in nasal washes was correlated with RW IgE in serum (r = 0.56, P less than 0.001, n = 44). RW IgG4 was detectable in NW of 15/22 pre-IT, 18/22 at 1 yr IT and 9/10 at 2 yr IT (P-values greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253091 TI - Production and characterization of monoclonal antibodies specific for human mast cell tryptase. AB - Human mast cell tryptase was purified from lung tissue by high salt extraction, ammonium sulphate precipitation, octyl Sepharose and heparin-agarose chromatography. The tryptase isolated was a tetramer with a molecular weight of 132 kD on gel filtration, and on SDS-polyacrylamide gel electrophoresis was reduced to a single diffuse band with a mean molecular weight of 32.5 kD. Purified tryptase catalysed the cleavage of the tryptic substrates tosyl L arginine methyl ester and benzoyl DL-arginine p-nitroanilide; enzymatic activity was enhanced in the presence of heparin but markedly decreased in the presence of 2 M sodium chloride. Rabbit antisera and three new monoclonal antibodies (AA1, AA3 and AA5) were produced which were specific for tryptase in indirect ELISAs, immunoenzymatic overlay in crossed immunoelectrophoresis and by Western blotting. Additive and competitive ELISA experiments suggested that the three monoclonal antibodies all recognized epitopes within a single highly immunogenic area of the tryptase molecule, and enzyme assays indicated that this site was distant from the active site. Binding of monoclonal antibodies to tryptase was not affected by the presence of heparin, or by periodate treatment of the antigen suggesting that carbohydrate epitopes were not recognized. Western blotting indicated that some heterogeneity in molecular weight for monomeric tryptase was not reflected in antigenic differences. An immunofluorescence procedure with cytocentrifuge preparations of enzymatically dispersed lung, colon and skin revealed highly specific localization of tryptase to the granules of all mast cells, but there was no binding to other cells in these preparations, to cultured keratinocytes, to basophils or to any other blood leucocyte. PMID- 2253092 TI - Aero-allergen avoidance in the prevention and treatment of asthma. PMID- 2253093 TI - Prediction of atopic disease in the newborn: methodological aspects. PMID- 2253094 TI - The role of the paediatrician in the management of allergy. PMID- 2253095 TI - Perinatal environmental factors influencing the development of allergy. PMID- 2253096 TI - Prevention of childhood allergy by dietary manipulation. PMID- 2253097 TI - [Etiology of intestinal obstruction--4 years' experience]. AB - In order to find out the etiological patterns of intestinal obstruction, we reviewed 1205 cases diagnosed as intestinal obstruction at our hospital. The operative findings, locations of obstruction and pathological results were analyzed among 707 cases who were operated on. The most common cause of colon obstruction was tumor (78.7%). The etiologies of small intestinal obstruction were: adhesions, 47.4%; hernia, 22.1%; tumor, 11.8%; intussusception, 8.8%; foreign bodies, 3.7%; and miscellaneous causes, 6.2%. In the patients older than 40 years, the most common causes of intestinal obstruction were adhesion and malignancy, in contrast to hernia and intussusception that were commonly found in children. The mean age of the patients with colon obstruction was older than those with small bowel obstruction, 55.7 +/- 21. vs 39.4 +/- 17.3 (P less than 0.001). Of the patients with previous abdominal surgery, adhesions caused the obstruction in up to 60.5%. Among the 102 cases who had been operated for abdominal malignancy, the cause of intestinal obstruction was due to recurrent tumor in 78 patients (76.4%). Of patients without previous abdominal surgery, the etiologies of intestinal obstruction were: incarcerated hernia, 36.7%; tumor, 21.1%; intussusception, 15.6%; and adhesion, 13.8%. The incidence of strangulation obstruction was 25.7%, of which the major causes were adhesions, 51.7%; and hernia. 43.0%. We concluded that the most common cause of colon obstruction was tumor. The two most common causes of small intestinal obstruction were adhesions and hernia. Age and past history of abdominal surgery can much help for the differential diagnosis. PMID- 2253098 TI - A comparative histopathological study of hepatic venous outflow obstruction in veno-occlusive disease and Budd-Chiari's syndrome. AB - Forty-two cases of hepatic venous outflow obstruction with biopsied and autopsied specimens were studied. The morphological changes in the liver and the value of liver tissue in the diagnosis among the different subgroups of this conditions were evaluated. Seven cases in the group with veno-occlusive disease (VOD) showed prominent changes in the sublobular veins and terminal hepatic venules and were characterized by acute disruption of the vessel walls. Two cases showed thrombosis in which there were history of chemotherapy. In the group with Budd Chiari's syndrome (BCS), in addition to the involvement of the large veins, thrombosis was observed in the small hepatic vein radicles in five out of six cases with myeloproliferative related disorders. Thrombosis was rarely present in cases associated with idiopathic and web lesions in BCS but frequent large vessel tumor thrombosis was noted in the group with malignant tumors. The hepatic parenchymal changes in the VOD group and the tumor related cases in BCS group were acute perivenular congestion, hemorrhage and coagulative necrosis, whereas the histological changes in other subgroups of BCS were perivenular scarring, dilatation of the sinusoids and rarely, reversed lobulation. Subtle differences were noted in the vascular system and the liver parenchyma between each subgroup. If good clinical information is available, it is possible to differentiate the various etiologies in hepatic venous outflow obstruction in the liver by morphology. PMID- 2253099 TI - [Speech outcome after early or delayed hard palate closure]. AB - Delayed hard palate closure (after age 6-7) was widely used for palatal repair in cleft palate children from 1976 to 1982. Since 1982, the approach has been revised into early complete closure of the soft and hard palate (before age 2). The articulation skills of 60 children with cleft lip and palate (age 3-5:11) who underwent early complete palate closure were compared with 47 children of similar age with soft palate closure only. The results indicated that the early complete closure group had more children with adequate articulation skills than the delayed hard palate closure group. Detailed analysis of the articulation patterns in each group revealed that the articulation substitution patterns made by the early complete closure group followed the trends of developmental articulation patterns, i.e. unaspirated, stopping and fronting phonological features. On the contrary, the articulation substitution patterns made by the delayed hard palate closure group were more related to structural deficits, i.e. compensatory articulation. Age 3-5 is a critical period for articulation maturation. We advocate that the complete palatal closure should be achieved before age 2 in order to equip cleft palate children with an equally normal oral structures to enhance speech/language development in a normal learning process during this critical period. PMID- 2253100 TI - Tibial fracture with or without fibular fracture--clinical studies. AB - This report investigated 145 cases of closed tibial fractures treated with closed reduction and cast immobilization, and followed up at least for 2 years, from 1981 to 1984, at Chang Gung Memorial Hospital of Taiwan. The total delayed or nonunion rate was 28.3% (41 patients), and the healing period was 4.6 months on average (range, 3-6 months). Among them, the delayed or nonunion rate in the tibial fractures with fibular fracture group was 33.3% (35/105), but in the tibial fractures without fibular fracture group it was only 15% (6/40). The difference between the groups was statistically significant (P less than 0.05). The severity of soft tissue injury may be a very important prognostic factor for bone healing. PMID- 2253101 TI - [Nevus sebaceus--a clinicopathological study of 104 cases]. AB - We studied the clinical and histopathologic features of 104 cases of nevus sebaceus observed between January 1983 and December 1988 in the department of Dermatology of Chang Gung Memorial Hospital. There were 48 males and 56 females, the ages ranged from 3 to 60 years, the mean age was 23.5 years old. Among them, most nevus sebaceus developed before age 10 (83%); the most common site of nevus sebaceus was the scalp (70%), followed by the face (26%) and only a few lesions were situated away from the head. Twenty-one cases were associated with secondary tumors in a portion of the lesions were found. In nineteen of the twenty-one patients, the secondary tumors occurred after age 10, their mean age was 30 years old. Of the 25 tumors developed in the 21 patients, 8 were syringocystadenoma papilliferum, 6 were basal cell epithelioma, 4 were trichilemmoma, 3 were sebaceous epithelioma. Multiple tumors were developed in 3 cases of nevus sebaceus. Since a variety of tumors may develop in the nevus sebaceus after puberty, prophylactic removal of nevus sebaceus and close follow-up are suggested. PMID- 2253102 TI - Gastrointestinal phytobezoar in children. AB - Phytobezoars are composed of fruit or vegetable matter, including seeds, nuts, and pits, and are the most common type of bezoar associated with gastrointestinal obstruction. Eleven gastrointestinal phytobezoar in children (less than 15 years old) seen within a period of 8 years (1981-1988) were analysed. Six were boys and 5 were girls. On history, 6 patients developed symptoms after ingestion of persimmon. All cases except one occurred in late fall and winter. In 8 patients, phytobezoar was found in a single location with 5 in the ileum and 3 in the jejunum. Multiple locations were found in 3 patients. Emergency laparotomy was performed on all cases who had typical mechanical intestinal obstruction. Treatment consisted of fragmentation of bezoar with pushing toward the cecum in 9 patients, combined with gastrotomy in 3 patients, and enterotomy in 2 patients. Because the persimmon ingestion is the most common cause of bezoar formation, a careful dietary history will usually suggest the diagnosis preoperatively. All the gastrointestinal tract should be thoroughly examined intraoperatively, especially the stomach and terminal ileum, to prevent another intestinal obstruction caused by an undiscovered phytobezoar. PMID- 2253103 TI - Ultrasonographic diagnosis of fetal cystic hygroma. AB - Prenatal diagnosis of seven cases of fetal cystic hygroma was characterized by multiloculated cystic mass with septated appearance in relation to the fetal head and neck, as well as various degree of lymphedema and peritoneal effusion and no direct communication with the central nervous system. Karyotype studies were performed in four cases and a composite of karyotypes from literatures is presented. The sonographic appearances and cytogenetic analyses will provide the significant framework needed for accurate prenatal diagnosis and genetic counseling. PMID- 2253104 TI - [Effect of topical fluoridation on post-radiation caries in patients with head and neck cancer]. AB - Post-radiation caries, a rapidly progressing and highly destructive type of dental caries, is one of the most common post- radiation complications in patients with head and neck cancer. Topical fluoride application has been shown in clinical studies to reduce post-radiation caries in irradiated patients. This study reviewed 148 patients who had received radiation for head and neck cancer. All the subjects received pre-radiation dental care. After radiation, the first group consisted of 53 patients who were under regular 3 months dental recall and received topical fluoride applications. The second group consisted of 95 patients who did not return for regular dental recall. Result from clinical examination and bitewing radiographs revealed that the caries indexes were 7% and 31% for the first and second groups, respectively. Chi-Square test showed significant difference between the two groups (P value less than 0.005). Regular topical fluoride application is valuable in reducing dental caries after radiation for head and neck cancer. PMID- 2253105 TI - [Delayed intracranial aneurysm of left atrial myxoma--a case report]. AB - Although embolism is known as a common complication in the early growing stage of atrial myxoma, development of further neurologic disorders after the removal of tumor is rarely encountered. Arterial aneurysm formation and metastatic tumor growth represent the two disorders that had been reported in the literature. Based on the pathogenesis of hematogeneous disseminating, atrial myxoma may lodge its fragment or its adherent thrombus on intracranial vessels to produce cerebral infarct. Besides, several reports have indicated that myxoma emboli in the cerebral vessels may invade the vessel wall to produce delayed disorders. Embolization from atrial myxoma is now recognized as a potentially treatable cause of cerebral infarct. However, the long-term course following resection of the tumor remain complicated, partly due to these inconsistent delayed complications, or the therapeutic dilemma. We report a case with delayed intracranial aneurysm formation and reviewed the literature. A 67-year old woman with a past history of left cerebral infarction was transferred to our hospital for further evaluation of her gross hematuria. Infarction of the left kidney was then demonstrated by angiography. A left atrial myxoma was found in a echocardiographic screen, and the patient received a successful resection of the myxoma subsequently. Unfortunately, three episodes of stroke developed in a half year after the operation of the cardiac myxoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253106 TI - [Leiomyosarcoma associated hypoglycemia--report of two cases]. AB - We report 2 cases of leiomyosarcoma associated hypoglycemia. Case 1 had had a tumor over his left thigh area for 13 years and a few episodes of hypoglycemia occurred when the tumor grew rather large (10 cm x 10 cm x 6 cm). Abdominal sonogram showed metastatic masses in the left lobe of liver. Hypoglycemia syndrome improved after chemotherapy, but relapse was noted later. Another case suffered from progressive abdominal distension for about one year and a huge mass (19 cm x 15 cm x 12 cm) over small intestine was found. Although surgical resection of the tumor and adjuvant chemotherapy was performed, recurrence of the tumor with hypoglycemia was noted. Both of the cases produced hypoglycemia in a fasting state rather than postprandial hypoglycemia. Hypoglycemia associated with non-islet cell tumor is one of the endocrinologic paraneoplastic Syndromes. The most common tumor found in this syndrome is sarcoma and such tumors are usually large when hypoglycemia is noted. Treatment of paraneoplastic hypoglycemia initially requires glucose infusion for acute symptomatic relief, then treatment of the underlying tumor. Reduction of tumor, radiotherapy or chemotherapy can improve the hypoglycemia syndrome, but it readily relapses. PMID- 2253107 TI - Pulmonary edema during ritodrine tocolysis--a case report. AB - A case of maternal pulmonary edema is presented as a late complication after intravenous administration of ritodrine in combination with dexamethasone for the suppression of premature uterine contraction and for the stimulation of fetal lung maturity. Swan-Ganz catheterization showed normal pulmonary capillary wedge pressures. Two-dimensional echocardiography disclosed good ventricular performance. The patient recovered very soon in 2 days post termination of pregnancy. Relative fluid overload might probably be responsible for the development of pulmonary edema in this case. PMID- 2253108 TI - Preliminary study on relationships among strains forming a bacterial community selected on naphthalene from a marine sediment. AB - Two bacterial strains were isolated from a bacterial community formed of nine strains, selected from a marine sediment on a seawater medium with naphthalene as sole carbon source. The two strains studied in the present work were the only strains of this community able to grow in pure culture on naphthalene; therefore, they were called "primary" strains. The seven other strains were maintained in the community by using metabolic intermediates of the two primary strains; they were called "auxiliary" strains. Regulation of naphthalene metabolism was studied for the two primary strains. They oxidized naphthalene into catechol, which was degraded only by the meta pathway. For Pseudomonas Lav. 4, naphthalene oxygenase and salicylate hydroxylase were inducible; catechol 2,3-dioxygenase was constitutive. For Moraxella Lav. 7, naphthalene oxygenase was constitutive; salicylate hydroxylase and catechol 2,3-oxygenase were inducible. The Moraxella strain carries two cryptic plasmids, about 63- and 85-kb in molecular size. In the bacterial community culture medium, Moraxella Lav. 7 prevented accumulation of 2-hydroxymuconate semialdehyde formed by Pseudomonas Lav. 4. The auxiliary strains take up formic, acetic, pyruvic, propionic, and succinic acids released by the two primary strains. PMID- 2253109 TI - Molecular size variation of the hemagglutinating adhesin HA-Ag2, a common antigen of Bacteroides gingivalis. AB - The array of Bacteroides gingivalis W83 antigens revealed by crossed immunoelectrophoresis includes one antigen that is associated with an erythrocyte binding capacity, termed the hemagglutinating adhesin HA-Ag2. This antigen was excised from crossed-immunoelectrophoresis plates to produce two polyclonal antisera, VL 011 and WL 303, whose restricted specificity for HA-Ag2 was assessed using crossed immunoelectrophoresis, crossed immunoelectrophoresis with an intermediate gel, and crossed immunoaffinoelectrophoresis. Both antisera, when used to probe blots of an EDTA cell surface extract of B. gingivalis W83, reacted with two bands, at 33 and 38 kDa, which were also detected by a monoclonal antibody (Naito et al. 1985. Infect. Immun. 50: 231-235), specific for a hemagglutinin of B. gingivalis. Antiserum WL 303 was used to examined by immunoblotting the distribution of HA-Ag2 among a variety of human and animal strains of B. gingivalis. All human strains tested showed two major bands at 33 and 38 kDa in the EDTA cell surface extract, and at 43 and 49 kDa in outer membrane preparations. Only one band, at 29 kDa, was detected in EDTA cell surface extracts from the animal strains, while the outer membrane preparation of a single strain showed a positive reaction. We concluded that HA-Ag2 is an antigen common to human and animal strains of B. gingivalis and that its subunits may show heterogeneity in apparent molecular mass. PMID- 2253110 TI - Accumulation of radiocaesium in fungi. AB - The accumulation of radioactive Cs by fungi was studied by analysis of fruit bodies (n (total) = 205, n greater than or equal to 5 for 22 species) collected in 1988 in a Norwegian mountain area with high deposition of radiocaesium from the Chernobyl accident. To account for site variation, the radiocaesium content of soil and plants was determined for each sampling spot. The soil contained 5 600 kBq/m2 (median = 50 kbq/m2, 134Cs + 137Cs). The plant content ranged from 0.25 to 23 Bq/g dry weight (median = 3.1 Bq/g) and was positively correlated with radiocaesium concentration in the soil (r = 0.56) and negatively correlated with soil pH (r = -0.28). The ratio between radiocaesium content in fungi and that in plants at the same spot (F/P) differed among species: 25 species had F/P values between 30 and 270, 12 species had F/P values between 10 and 30, and the rest (16 species) had F/P values below 10 (only four samples had values below 1). The concentration of nonradioactive Cs in fruit bodies was positively correlated with their radiocaesium content. Certain species selectively accumulated one or several trace elements (V, Cd, Hg, Pb, Th). PMID- 2253111 TI - Soluble factors from rabbit spleen cells kill and lyse Treponema pallidum in vitro. AB - Antibody and complement immobilize (kill) Treponema pallidum in vitro. Recent evidence also documents immobilization by soluble factors released by activated macrophages and lymphocytes. Immune-mediated lysis of treponemes, however, has not been reported. The findings in this paper focus on apparent treponemal lysis by rabbit splenic cell preparations. Using cells from animals infected testicularly for 9 to 12 days, unfractionated splenic preparations, as well as adherent and nonadherent preparations, killed and lysed T. pallidum. Phagocytosis alone could not explain the detrimental effects of adherent cells. When cytochalasin B was used to block phagocytosis, decreases in treponemal numbers were still detected. In related studies, immune rabbit sera did not enhance treponemicidal activity of the adherent cells. To assess the specificity of these reactions, T. pallidum was incubated with two monocyte-like cell lines (human U937 and mouse P388D1). Neither cell line was detrimental, and treponemal numbers were not lowered. The soluble nature of the treponemicidal factors from adherent and nonadherent preparations was shown by physically separating these cells from the organisms and demonstrating treponemal killing and lysis. In summary, clearance of T. pallidum from infected tissues is probably at least partially attributed to macrophage phagocytosis. Our findings suggest another mechanism involving lytic factors secreted by activated adherent and nonadherent cells. PMID- 2253112 TI - Expression of dibenzothiophene-degradative genes in two Pseudomonas species. AB - The genes encoding dibenzothiophene (DBT) degradation in Pseudomonas alcaligenes strain DBT2 were cloned into plasmid pC1 by other workers. This plasmid was conjugally transferred into a spontaneous variant of Pseudomonas sp. HL7b (designated HL7bR) incapable of oxidizing DBT (Dbt- phenotype). Acquisition of plasmid pC1 simultaneously restored oxidation of DBT and naphthalene to the transconjugant, although the primary DBT metabolite produced by transconjugant HL7bR(pC1) corresponded to that produced by wild-type strain DBT2 rather than that from wild-type strain HL7b. Inducers of the naphthalene pathway (naphthalene, salicylic acid, and 2-aminobenzoate) stimulated DBT oxidation in transconjugant HL7bR(pC1) when present at 0.1 mM concentrations but had no effect on wild-type strain HL7b. Higher concentrations (5 mM) of salicylic acid and naphthalene were inhibitory to DBT oxidation in all strains. DNA-DNA hybridization was not observed between plasmid pC1 and genomic DNA from strains HL7b or HL7bR, nor between authentic naphthalene-degradative genes (plasmid NAH2) and either plasmid pC1 or strain HL7b, despite the observation that the degradative genes encoded on plasmid pC1 functionally resembled broad-specificity naphthalene-degradative genes. Transconjugant HL7bR(pC1) is a mosaic of the parental types regarding DBT metabolite production, regulation, and use of carbon sources. PMID- 2253113 TI - Optimization of 7 alpha-hydroxysteroid dehydrogenase production by Escherichia coli 080. AB - 7 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.159) production by Escherichia coli strain 080 was highest when the organism was grown in brain heart infusion broth at pH 6.5 for 72-96 h with shaking at 37 degrees C. The oxygen consumption rate had a strong effect on the production of this constitutive enzyme. Glucose and lactose at 0.2-0.4%, detergents, and ethylenediaminetetra-acetic acid were found to increase the enzyme production. PMID- 2253114 TI - Homology among bacterial catalase genes. AB - Catalase activities in crude extracts of exponential and stationary phase cultures of various bacteria were visualized following gel electrophoresis for comparison with the enzymes from Escherichia coli. Citrobacter freundii, Edwardsiella tarda, Enterobacter aerogenes, Klebsiella pneumoniae, and Salmonella typhimurium exhibited patterns of catalase activity similar to E. coli, including bifunctional HPI-like bands and a monofunctional HPII-like band. Proteus mirabilis, Erwinia carotovora, and Serratia marcescens contained a single band of monofunctional catalase with a mobility intermediate between the HPI-like and HPII-like bands. The cloned genes for catalases HPI (katG) and HPII (katE) from E. coli were used as probes in Southern hybridization analyses for homologous sequences in genomic DNA of the same bacteria. katG was found to hybridize with fragments from C. freudii, Ent. aerogenes, Sal. typhimurium, and K. pneumoniae but not at all with Ed. tarda, P. mirabilis, S. marcesens, or Er. carotovora. katE hybridized with C. freundii and K. pneumoniae DNAs and not with the other bacterial DNAs. PMID- 2253115 TI - Antituberculous drug susceptibility testing of Mycobacterium bovis BCG strain Montreal. AB - Testing of Mycobacterium bovis BCG strain Montreal for susceptibility to four primary antituberculous drugs (isoniazid, ethambutol, streptomycin, and rifampin) and to one secondary drug (p-aminosalicylic acid) showed the strain to be susceptible to all five substances. Mycobacterium bovis strains ATCC 35735, which is isoniazid sensitive, and ATCC 35747, which is isoniazid resistant, were included in the test; with the exception of their respective susceptibility to isoniazid, both were inhibited by the other four drugs. PMID- 2253116 TI - Pelvic ring fractures. PMID- 2253117 TI - Perforated sigmoid diverticulum occurring after surgery. PMID- 2253118 TI - Update on trauma care in Canada. 1. Recent advances in thermal injuries. AB - Thermal injury frequently occurs in traumatized patients in North America and causes serious morbidity and mortality, predominantly to children and young adults. Over the past decade, considerable technologic advances have improved survival after burn injury. Ongoing research coupled with current surgical advances in equipment, technique, early wound closure and alternative forms of wound coverage offer the potential for greater survival with enhanced quality of life for traumatized patients with burn injuries. However, sepsis and inhalation injury remain important ongoing causes of death, for which the understanding and solutions appear to be unfolding as research into the multisystem effects of the inflammatory process continues. PMID- 2253119 TI - Update on trauma care in Canada. 2. Update on pediatric trauma. AB - Selective conservatism is the key to the rational management of pediatric trauma, realizing that children may harbour severe occult injuries. The modern treatment of childhood abdominal trauma best exemplifies this approach: nonoperative management of splenic trauma is now standard for children, and a selective conservative approach is advised in the handling of childhood liver and pancreatic injuries. Prevention of childhood injuries should be the goal. The development of a national database of childhood trauma should provide the basis for action to educate and legislate for prevention. When prevention fails, however, up-to-date quality pediatric trauma care is the key. PMID- 2253120 TI - Update on trauma care in Canada. 3. Pelvic ring fractures. AB - Correct assessment and treatment of pelvic ring fractures in the multiply injured patient is important because it can result in fewer deaths and less long-term disability. There is ample evidence to show that surgical stabilization of unstable pelvic ring fractures is a life-saving intervention that should be done on the day of injury. Anterior frame external fixation is the standard form of treatment and is life-saving. However, it is not ideal biomechanically, and over the next decade open reduction and internal fixation of pelvic ring fractures will likely become the treatment of choice. PMID- 2253122 TI - Update on trauma care in Canada. 5. Trauma and hypothermia. AB - Trauma may be accompanied by hypothermia in all climates. Because of the associated increased death rate due to hypothermia (core body temperature less than 35 degrees C), traumatized patients must be protected from it. The body maintains heat balance by hypothalamic regulation of endogenous heat generation and heat loss. Decreased core temperature causes generalized physiologic deceleration and homeostatic disturbances in all organ systems. To prevent hypothermia in polytraumatized patients a number of methods may be used: warming crystalloid, increasing ambient temperature, the use of warming devices, irrigation of body cavities with warmed fluids, heating of inspired gases and, in severe cases when there is circulatory instability, the use of extracorporeal membrane oxygenation. PMID- 2253121 TI - Update on trauma care in Canada. 4. Resuscitation through the three phases of hemorrhagic shock after trauma. AB - There are three phases of acute hemorrhagic shock after trauma. In phase I (from injury to operation for control of bleeding) the patient suffers from low cardiac output, tachycardia, reduced organ perfusion, oliguria and decreased capillary hydrostatic pressure, which in turn reduces extravascular fluid loss. Contraction of the interstitial space matrix replenishes plasma volume. Optimal therapy includes blood and crystalloid replacement to restore plasma volume, red cell mass and interstitial fluid. Three litres of crystalloid are usually required for each litre of blood lost. After operation, a period of obligatory extravascular fluid sequestration occurs as the intracellular and interstitial spaces expand (phase II). Optimal replacement therapy during this phase maintains plasma volume. Replacement is provided according to the patient's vital signs, because extravascular fluid expansion cannot be influenced by therapeutic manipulation. Phase III is a mobilization and diuretic phase. During this phase systolic hypertension may occur, and the patient must be treated with restriction of fluid, diuresis and careful monitoring of the heart and lungs. Attempts to alter these physiologic responses with supplemental albumin have proved detrimental. The albumin causes salt and water retention in the nephron, leading to weight gain, higher central filing pressures and worsening pulmonary function, and a greater need for diuretic and inotropic therapy. Albumin therapy also induces relocation of non-albumin proteins into the interstitial space, leading to impaired immunocompetence and coagulation. Successful resuscitation is facilitated by adaptation to these physiologic responses of hemorrhagic shock rather than manipulation of them. PMID- 2253123 TI - Update on trauma care in Canada. 6. Update on trauma registries and trauma scoring. AB - Developments in microcomputer technology and user friendly software have resulted in rapidly expanding interest in trauma registries and injury scoring. The trauma registry, particularly when it is population based, is an empowering tool for epidemiologic research, planning of trauma systems, development of prevention programs, outcome evaluation and research. Injury coding performed in conjunction with trauma registry can also provide the basis for institutional quality assurance. The Major Trauma Outcome Study has played a major role in this, through the development of normative standards, permitting inter-institutional comparisons. These issues as well as some of the present Canadian and American initiatives in the trauma registry field are reviewed in this paper. Advances in injury scaling are addressed as are some of the limitations in existing coding methodologies. PMID- 2253124 TI - Aortic dissection: current expectations and treatment. Experience with 258 patients over 20 years. AB - Aortic dissection, the most common acute disease of the thoracic aorta, is associated with high mortality and morbidity. The authors reviewed their experience over the last 20 years with 258 patients who had aortic dissection (259 dissections). The diagnosis was made at autopsy in 69 (27%) patients (59 type A, 10 type B). Of the remainder, 97 patients had type A dissection (78 acute, 19 chronic) and 93 had type B dissection (56 acute, 37 chronic). The sudden onset of severe, unremitting chest pain associated with hyper- or hypotension or a history of hypertension are suggestive of acute aortic dissection. The diagnosis should be followed by prompt investigation and treatment. The 30-day survival rate for patients with type A dissection who underwent surgical treatment was 62%; survival rates for patients with type B dissection, acute and chronic, were 70% and 86% respectively with pharmacotherapy and 66% and 91% with surgery. The authors stress the importance of early, accurate diagnosis and immediate surgical treatment for all patients who have type A dissection and complicated or unresponsive (carefully monitored pharmacologic control of blood pressure) type B dissection. PMID- 2253125 TI - Determination of operability in candidates who undergo lung resection for bronchogenic carcinoma. AB - In this prospective study the authors attempted to determine the effect of lung resection for bronchogenic carcinoma on final pulmonary function in patients who had severe limitation of lung air flow preoperatively and were therefore likely to have severe, progressive pulmonary failure and in those who had acceptable pulmonary function preoperatively. Preoperative and postoperative pulmonary function tests were performed on 20 patients chosen to undergo various types of resection for bronchogenic carcinoma. Those who underwent pneumonectomy had changes in lung volume that were expected for a resection of that magnitude. Patients who underwent lesser resections had more variable postoperative lung volumes and flows. The patients whose preoperative pulmonary function was poorest had the least change postoperatively and even, in some cases, showed some improvement in function, yet they were the ones most likely to be denied surgery, because of their poor preoperative pulmonary function. PMID- 2253126 TI - Improvement in thoracic aortic pressure after proximal aortic cross-clamping by balloon occlusion of the distal aorta. AB - Spinal cord hypoperfusion injury is a devastating complication of cross-clamping the proximal thoracic aorta. The collateral circulation around the cross-clamp is generally poorly developed, and the run-off is immense, resulting in extremely low thoracic aortic and spinal cord perfusion pressures. The authors postulated that balloon occlusion of the abdominal aorta might confine this reduced collateral flow around the cross-clamp to the thoracic aorta. In 8 of 16 dogs subjected to aortic cross-clamping of the aorta just beyond the arch vessels, the abdominal aorta was also occluded by a balloon. Thoracic aortic pressure and spinal cord perfusion pressure were significantly higher in the animals with aortic balloon occlusion than in those without balloon occlusion (77 +/- 8 mm Hg versus 26 +/- 1 mm Hg, p less than 0.01, and 67 +/- 8 mm Hg versus 18 +/- 2 mm Hg, p less than 0.01, at 10 minutes after cross-clamping). Abdominal aortic balloon occlusion increases thoracic aortic pressure after the aorta is cross clamped proximally. Further studies are necessary in primates to assess the effect of this procedure in spinal cord perfusion and the rate of paraplegia. PMID- 2253127 TI - Renal cell carcinoma: incidental detection. AB - The mode of presentation of renal cell carcinoma is changing; in 40% of cases the condition is now found incidentally during the investigation of complaints other than those usually associated with this tumour. Chemotherapy and radiotherapy have not improved the survival of patients with renal cell carcinomas, but, with the introduction of ultrasonography, renal cell carcinomas, including those found incidentally, are being diagnosed earlier than they were a decade ago, resulting in improved survival rates. PMID- 2253128 TI - Long-term pain and disability in relation to residual deformity after displaced pelvic ring fractures. AB - In a retrospective review and follow-up study of 43 patients who had had high energy pelvic fractures 5 or more years earlier, the occurrence of late pain and the functional outcome were adversely related to residual deformity of the pelvic ring. Among patients who had no residual deformity (displacement less than 1 cm), 88% had no serious pain and 82% had normal function. Of patients who had residual deformity (displacement more than 1 cm posteriorly), only 30% had no serious pain (p less than 0.01) and only 30% had normal function (p less than 0.01). Definitive reduction and stabilization is therefore recommended early after the injury whenever possible. PMID- 2253129 TI - Laser-assisted balloon angioplasty: initial 18 months' experience. AB - The authors describe their initial 18-month experience with laser-assisted balloon angioplasty (LABA) of femoral arteries in 44 patients. Primary patency was achieved in 28 patients, but within 30 days the artery became occluded in 9 of them. Perforation occurred much more frequently early in the study. Complications associated with antegrade femoral artery puncture have led to more liberal use of LABA through an operative approach in the femoral artery. Attention to technical detail is critical. When LABA fails it does not appear to worsen the patient's condition clinically or radiologically. Endovascular procedures are undergoing continued, rapid change, so ongoing development and assessment of results are necessary for those who perform LABA. PMID- 2253130 TI - Malignant transformation occurring in mature cystic teratomas of the ovary. AB - Two cases in which tumours of contrasting malignant potential arose in mature cystic teratomas (dermoid cysts) of the ovary are presented: one patient had a spindle-cell sarcoma and the other a trabecular carcinoid. The first patient's clinical course was characterized by rapid recurrence of the tumour and death 3 months after surgery. The second patient is alive and well with no evidence of residual carcinoid, although the follow-up time is short. Since the surgical procedure of choice differs substantially if malignant transformation occurs in an ovarian dermoid cyst, the pathologist should be consulted intraoperatively in selected cases. PMID- 2253132 TI - Coronary artery bypass surgery rates in Ottawa. PMID- 2253131 TI - The national AIDS strategy is a start, nothing more. PMID- 2253133 TI - The Medical Reform Group has a purpose. PMID- 2253134 TI - Safety of contrast media. PMID- 2253135 TI - Periodic health examination, 1990 update: 3. Interventions to prevent lung cancer other than smoking cessation. PMID- 2253136 TI - When your husband turns 50. PMID- 2253137 TI - Error, ignorance and fraud. PMID- 2253138 TI - Why are clinical problems difficult? General practitioners' opinions concerning 24 clinical problems. AB - This study was conducted to describe the difficulties perceived by general practitioners concerning 24 common clinical problems and to compare their perceptions with those of faculty members in family medicine. A random sample of 467 general practitioners and all 182 faculty members in family medicine in Quebec were sent one of four open-ended questionnaires, each of which dealt with six clinical problems; 214 general practitioners and 114 faculty members participated. A total of 5111 difficulties were reported; the number reported by each subject varied from 0 to 13 (mean 2.6 [standard deviation 2.09]) per problem. The problems that generated the most difficulties were depression, confusion in the elderly, chronic back pain, loss of autonomy in the elderly and sexually transmitted disease. The most frequent difficulties were with the patient's noncompliance with treatment, clinical diagnosis, failure of a specific treatment, inadequate health care resources and the physician's own emotional reactions. The difficulties for each problem were the same in the two groups 70% of the time. Physician's perceptions of their difficulties can be useful in the planning of initial training and continuing medical education. PMID- 2253139 TI - Plasma therapy for severe hemolytic-uremic syndrome in children in Atlantic Canada. AB - Clinical reports have suggested that therapy with fresh frozen plasma is a useful adjunct in the management of the hemolytic-uremic syndrome (HUS). We reviewed the charts of 36 children with severe HUS who were treated at the Izaac Walton Killam Hospital for Children, Halifax, over 10 years to assess the effectiveness of plasma therapy. All children who required specific supportive therapy for renal dysfunction, hemolysis or serious extrarenal complications were included. We compared the outcome of 18 children who received plasma therapy from 1982 to 1987 with that of 18 children who did not. The two groups were similar with regard to the severity of HUS, the length of hospital stay, the duration of renal dysfunction and the incidence of disease-related complications, such as seizures, enterocolitis and cardiomyopathy. At discharge the prevalence of hypertension was higher in the plasma therapy group than in the control group. Plasma therapy did not demonstrate any benefit that would outweigh the risk of fluid overload, hyperproteinemia and transmission of viral infection. PMID- 2253140 TI - Miliary blastomycosis and HIV infection. PMID- 2253141 TI - Gene-environment interactions and atherosclerosis. PMID- 2253142 TI - Speakers offer vastly different views on disposable health care products. PMID- 2253143 TI - Organ nonretrieval rate remains high because "people are not being asked". PMID- 2253144 TI - We could learn a lesson from Kenya's midwives. PMID- 2253145 TI - SOGC issues guidelines for responding to federal abortion law. PMID- 2253146 TI - Schweitzer's example still shines. PMID- 2253147 TI - "Get yourself a new heart": Judaism and the organ transplantation issue. PMID- 2253148 TI - Influenza immunization in Canada. PMID- 2253149 TI - Combatting sexual assault: an evaluation of a prevention program. AB - Few guidelines exist for the planning or evaluation of community-based sexual assault prevention initiatives. Records from the Safety Van Program, as well as survey data from 60 users and 60 non-users characteristic of the target group, were used to explore the complex relationship between awareness, fear of assault and service use. Findings from the evaluation address issues such as basing program expansion on utilization rates, and using incidence rates to justify service need. PMID- 2253150 TI - Effects of residential exposure to environmental tobacco smoke on Canadian children. AB - The effects of residential exposure to environmental tobacco smoke were studied in a sample of 6,529 Canadian children under 15 years of age. Univariate analysis indicated an elevated risk of bronchitis among children whose mothers were single, or under age 25, or whose income or educational level was low. Multivariate analysis indicated that the relative risk of bronchitis among children whose mothers were current smokers relative to those whose mothers never smoked was 3.0 (95% CI:1.6,5.2). Significant dose-response relationships between risk of bronchitis and amount smoked as well as duration of exposure were observed. Using the composite exposure score of all smokers in the household as the source of exposure, the risk of bronchitis decreased slightly but remained significantly elevated. Examination of the risk conferred by the mother's smoking relative to the total household exposure showed that most of the elevation in risk was associated with the mother's smoking contribution. Asthma was also studied, but failed to show a statistically significant association with smoking. PMID- 2253151 TI - The prevalence of smokeless tobacco use in native children in northern Saskatchewan, Canada. AB - We used a self-administered questionnaire to develop a profile of smokeless tobacco use among 1,170 Canadian native children aged 7 to 21 years attending schools situated in remote communities in northern Saskatchewan. Nearly 30% of the sample were current users of smokeless tobacco; more than 50% of users began to use these products before the age of 12 years. More males than females chewed tobacco or dipped snuff. The results revealed a relatively high prevalence of smokeless tobacco users among the present sample of native children and were found to be consistent with data from other studies of similarly aged native populations. The results also showed a prevailing pattern of addiction among the users of smokeless tobacco. It is suggested that educational programs aimed at preventing or reducing the use of tobacco products among native populations be intensified and as well, these programs would benefit from the active participation of trained native personnel. PMID- 2253152 TI - Giardiasis outbreak from a chlorinated community water supply. AB - A giardiasis outbreak from a chlorinated, unfiltered surface water supply in Penticton, British Columbia (pop. 25,000) from June to August 1986 resulted in 362 laboratory-confirmed cases. A telephone survey estimated an attack rate of over 12%. A reservoir pond containing Giardia-infected beaver was implicated as the source. A case-control study with 65 cases did not find any significant associations. A retrospective case-finding survey of records from eight (out of 35) general physicians estimated that 1,500 physician visits occurred and produced an epidemic curve in close parallel with that from laboratory-confirmed and reported cases. Despite improvements on the reservoir, another outbreak occurred when this water source was reinstituted in October for several weeks, confirming our conclusion that it was the source of the first outbreak. Various options for reducing the risk of future outbreaks are being explored including full water treatment. PMID- 2253153 TI - [Selection of target behaviors before planning health education objectives: application to prevention of STD in teenagers]. AB - This article describes a semi-quantitative technique enabling the person responsible for the planning of a health education program to select the behaviour that should be targeted. The technique is adapted from Morley and used within Green's health education planning model. The relevant behaviours are ranked according to their importance and their changeability. A global weight is calculated for both by multiplying the weights attributed for each criterion of importance and changeability. This method is illustrated by an application for sexually transmitted diseases in teenagers. Calculations are made both for younger and older teenagers. PMID- 2253154 TI - The effects of nutritional quality and frequency of consumption of sugary foods on dental caries increment. AB - This study investigates the association of dietary quality with dental caries increment of 11-year-old children. A 3-day dietary record including one weekend day was completed by the subjects and their parents. The nutritional quality was evaluated using a quality index based on the eating frequency of foods recommended in food guides and divided into 8 levels. The frequency of consumption of sugary foods, liquid and solid, at and between meals was also calculated. Two oral examinations 20 months apart were made in 1983-85; each time, the quality of oral hygiene was determined by using the simplified oral hygiene was determined by using the simplified oral hygiene index of Greene and Vermillon. the dental caries increment between the two examinations was evaluated using the DMFS index. When the subjects were distributed into 3 groups according to their nutritional quality index, the mean dental caries increment had a tendency to decrease as the nutritional quality increased for the total sample as well as for boys and girls considered separately; however, the analysis of variance did not reveal any differences of statistical significance. No association was established for children in this study between frequency of consumption of sugary foods and caries increment. No association was observed between nutritional quality and oral hygiene nor between the mother's education and the children's frequency of consumption of sugary foods. Thus, in our study, children with the highest dental caries increment are not necessarily the ones having a diet of poor nutritional quality nor the ones consuming sugary foods more frequently. PMID- 2253155 TI - Premature deaths in Canada: impact, trends and opportunities for prevention. AB - The impact, time trends and potential for prevention of premature deaths in Canada were assessed. There were almost 100,000 deaths before age 75 in Canada during 1986 resulting in over 1.7 million potential years of life lost (PYLL). The three leading broad disease categories responsible for PYLL were cancer, injuries/violence and cardiovascular disease. In both sexes, coronary heart disease, car accidents, lung cancer and perinatal conditions ranked in the top 5 specific diseases responsible for PYLL; breast cancer (females) and suicide (males) also ranked in the top 5 conditions. Over the period 1969 to 1986, death rates among persons less than age 75 increased for 3 conditions among females and 11 conditions among males. Lung cancer and brain cancer death rates increased in both sexes, chronic obstructive pulmonary disease death rates increased among females only and death rates for suicide and 8 types of cancer increased among males only. Over the same period, death rates declined for 37 discrete disease categories among both females and males including particularly large improvements for coronary heart disease, stroke, car accidents and perinatal conditions. An estimated 50,000 or over 50% of all premature deaths per year are preventable through control of smoking, hypertension, elevated serum cholesterol, diabetes and alcohol abuse. About 6,000 premature deaths are avoidable through improvements in medical care. PMID- 2253156 TI - [Aging and technology: physical condition in a post-industrial society]. AB - Compulsory retirement, normally set at 65, may be considered discriminatory by people who wish to continue in their current employment to a greater age. The aging process sometimes limits the performance of daily work, particularly in occupations that demand a high rate of energy expenditure. However, this is not a general rule; there are many individuals older than 65 years (particularly those who have remained physically active) who can still carry out moderate physical tasks without fatigue. This article reviews various aspects of occupation, including the evaluation of work performance, and the beneficial effects of programs designed to increase functional capacity in the context of compulsory retirement. Biological age seems a useful criterion in deciding upon the appropriateness of mandatory retirement when reviewing individual cases. The authors recommend adopting a form of health hazard appraisal and measures of physical condition (including aerobic power, muscular strength and reaction time) as a part of such an evaluation, while recognizing the need for more precise methods of identifying those who can remain in gainful employment beyond the age of 65 years. PMID- 2253157 TI - The association between aversive and pleasurable oral sensations and oral health behaviour. PMID- 2253158 TI - Mental health services in Edmonton: an assessment of service availability. PMID- 2253159 TI - Is cervical cancer increasing among young women in Canada? PMID- 2253160 TI - Are we ready for international consultation? PMID- 2253161 TI - Health care spending as a risk to health. PMID- 2253162 TI - Smokers--hazards on road? PMID- 2253163 TI - Historic perspective of lesser metatarsalgia. AB - Metatarsalgia is often a catch-all word. This article discusses metatarsalgia in general and gives guidelines based on the combined experience of the authors. PMID- 2253164 TI - Lesser metatarsalgia. PMID- 2253165 TI - Differential diagnosis of lesser metatarsalgia. AB - Pain in the lesser metatarsophalangeal area of the foot remains a diagnostic challenge. This pathology often is attributed to neuromas. These painful lesions, although predisposed to this area, are not nearly as common as they are thought to be. The "systems approach" to diagnosis can be extremely helpful in establishing an accurate cause and subsequent proper diagnosis of lesser metatarsophalangeal joint pain. PMID- 2253166 TI - Soft-tissue causes of metatarsalgia. AB - A soft-tissue cause should always be considered when evaluating metatarsalgia. The history, examination, and plain radiographs can all suggest an avenue of pursuit, be it a potential dermatologic, connective tissue, vascular, neurologic, muscular, or neoplastic process. PMID- 2253167 TI - Lesser metatarsalgia evaluation and treatment. AB - Anatomic and biomechanical aspects of the complex topic of metatarsalgia are reviewed. Cause is classified as structural, functional, and a combination of both. Evaluation of the lesion symptom complex is presented and light is shed on reasons for complications after metatarsal osteotomy. Ways to avoid complications are also discussed. The oblique osteotomy with rigid fixation performed at the distal surgical neck or the proximal metaphysis is recommended. PMID- 2253168 TI - Freiberg's disease and dislocation of the second metatarsophalangeal joint: etiology and treatment. AB - Surgical and conservative treatments, based on historic and current concepts, are presented for management of Freiberg's disease and dislocation of the second metatarsophalangeal joint. A preliminary review of the interpositional arthroplasty used at the University of Texas Health Science Center is presented. PMID- 2253169 TI - Lesser metatarsal stress fractures: a study of 37 cases. AB - A study of lower-extremity stress fractures is presented with emphasis placed on metatarsal stress fractures. The metatarsals were found to be the second most common site in the study. The study documents not only the number of metatarsal stress fractures found, but also the location within the affected metatarsal. Because stress fractures are a common problem, especially for the military recruit or athlete, metatarsal stress fractures can represent a common cause of metatarsalgia. PMID- 2253170 TI - Pathology of the fifth ray, including the tailor's bunion deformity. AB - Pathology of the fifth ray has been reviewed with emphasis on the tailor's bunion. Based on a thorough radiographic analysis, the bunionette has been grouped into four types, and surgical criteria has been proposed. The goal of this study is to provide guidelines that may enable both podiatric and orthopedic surgeons to recognize the types of tailor's bunions and assist in the selection of an appropriate surgical procedure. PMID- 2253171 TI - Sesamoids and accessory bones of the foot. AB - This contribution presents the major pathologic findings and causes of sesamoid disease. The reader will appreciate the thoroughness of this article. PMID- 2253172 TI - Ulceration and osteomyelitis. AB - The pathophysiology, mortality, and morbidity of osteomyelitis and ulcers are discussed, including making the diagnoses. Treatments described include topical and surgical methods as well as hyperbaric oxygen therapy. PMID- 2253174 TI - Lesser metatarsalgia. Rheumatologic considerations. AB - The differential diagnosis for metatarsalgia should include rheumatoid arthritis, SLE, mixed connective tissue disease, psoriatic arthritis, Reiter's syndrome, fibromyalgic syndrome, gout, post-traumatic joint disease, and septic arthritis. When the patient's symptoms are approached systematically an accurate diagnosis can lead to implementation of an appropriate treatment plan. Multidisciplinary treatment approaches often lead to the most satisfying therapeutic outcomes. PMID- 2253173 TI - Lesser metatarsalgia in the geriatric patient. AB - This segment provides a classic definition of the clinical condition as it presents in the older patient. This article discusses causative considerations as they relate to aging and management and related aspects involved in the care of the older patient. PMID- 2253175 TI - Pathomechanical metatarsal arc: radiographic evaluation of its geometric configuration. AB - A total nonlinear relationship among all five metatarsals is presented in this article. This relationship is an equation whose graph is a conic curve. The metatarsal arc is defined as a conic curve that has a unique numeric value, its eccentricity. Thus, each metatarsal arc variation has a unique eccentricity value, an axis location value, and a coefficient of variation value. It is assumed that many of these metatarsal arc variations are pathomechanical, and that an optimal arc exists. A small sample yielded numeric values that appear to be related to the degree of pathomechanical variation. Based on a small sample, clinical experience, and a numeric classification that is theoretically attractive, it is recommended that the surgeon plan each case of forefoot surgery so that these numeric values are given due consideration in the establishment of a geometric configuration for the metatarsal arc. To obtain these numeric values, the surgeon can learn to analyze the radiographs mathematically or submit them to someone who can. PMID- 2253176 TI - Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease. AB - A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease. PMID- 2253177 TI - Cytogenetics of three cases of ANLL M2 and M4. Involvement of chromosomal region 8q22 in all three but 21q22 in only one. AB - Cytogenetic investigation of the bone marrow of two patients with acute nonlymphocytic leukemia (ANLL), French-American-British Cooperative group (FAB) classification M2, revealed a translocation (8;22)(q22.1;q13.3), without involving chromosome 21, and a variant translocation (8;21)(q22;q22). These findings, together with a del(8)(q22) found in a patient with refractory anemia, erythroblastic (RAEB)-t with progression to acute myelogenous leukemia (AML)-M4, are discussed in relation to the possible role of abnormalities of chromosomes 8 and 21 in the oncogenesis of ANLL M2 and M4. PMID- 2253178 TI - Cytogenetic findings in patients with acute promyelocytic leukemia and a case of CML blast crisis with promyelocytic proliferation. AB - Nineteen patients with acute promyelocytic leukemia (APL) and one with promyelocytic blast crisis were studied by a methotrexate cell synchronization technique and by 24-hour short-term culture. Nineteen cases of APL included two cases of the microgranular variant (M3V). Except in one case of M3V, t(15;17) was detected in all patients. The breakpoints were determined as 15q22 and 17q12-21. A chronic myeloid leukemia (CML) blast crisis patient with high promyelocyte count also had a t(15;17) as well as a masked Ph chromosome. Other abnormalities, such as +8,del(7q) and an i(17q), were also observed in some patients. Our studies have indicated that 1) the translocation (15;17), characteristic of APL, was present in our population in almost all patients; 2) the presence of an identical abnormality in a promyelocytic CML blast crisis supported and confirmed the phenomenon of association of specific chromosome change with target cell type; and 3) the precise localization of breakpoints on chromosome 17 is still difficult to determine. The identification of as yet unknown genes at region 17q11-q21 and their subsequent translocation on chromosome 15 will help in assigning a precise position to these breakpoints. PMID- 2253179 TI - Cancers in 44 families with ataxia-telangiectasia. AB - Cancer incidence was measured retrospectively in 574 close blood relatives of white ataxia-telangiectasia (A-T) patients and 213 spouse controls in 44 previously unreported families. The cancer incidence rate in the adult blood relatives was significantly elevated over the rate in the spouse controls (rate ratio = 3.9, p less than 0.01). For heterozygous carriers of the A-T gene, the relative risk of cancer was estimated to be 6.1 (p less than 0.005) as compared with nonheterozygotes. The most frequent cancer site in the blood relatives was the female breast, with nine cancers observed. These findings provide further support for the hypothesis that heterozygotes for the A-T gene are predisposed to cancer. PMID- 2253180 TI - Symmetrical chromosome rearrangements in cell lines established from human radiation-induced sarcomas. AB - We report the establishment of cell lines from six radiation-induced tumors, three osteosarcomas, and three soft tissue sarcomas. Cytogenetic analysis of the lines showed mostly balanced rearrangements in the osteosarcomas; the soft tissue sarcomas had more unstable karyotypes. The rearrangements observed were unlike those previously reported for spontaneously occurring tumors of the same histological type and were more typical of the long-term changes observed after radiation exposure. PMID- 2253181 TI - Correlation between in vitro tetraploidy in skin fibroblasts and development of sporadic colorectal carcinomas. AB - In vitro tetraploidy (IVT) in skin fibroblasts cultures measured by flow cytometry was compared with histological type and degree of dysplasia in 22 patients with adenomas of the colon and rectum. Furthermore, IVT was compared with stage and differentiation in 36 patients with carcinoma of the colon and rectum. In vitro tetraploidy in skin fibroblasts was correlated to type as well as dysplasia in adenomas and differentiation in carcinomas but was not correlated to Dukes' stage in carcinomas. Skin fibroblast genetic instability, expressed as increased IVT (IVT+), has been reported to reflect a genetic predisposition to colorectal cancer in the hereditary nonpolyposis colorectal cancer syndrome. Because IVT+, which appears to be associated with the progression of adenomas to carcinomas, also is found in many of the non-syndrome colorectal cancers, we suggest that development of colorectal cancer is considerably influenced by the constitutive genetic instability of the autosomal dominant colorectal cancer syndromes. PMID- 2253182 TI - Appearance time of leukemic cells with t(8;21) in bone marrow. AB - A 30-year-old man was referred because of slight leukocytosis. The hematological findings, including those of the bone marrow, showed no evidence of leukemia. The level of neutrophil alkaline phosphatase (NAP) in the peripheral blood was normal, as were the chromosomes from bone marrow cells. Fifteen months later, the disease was diagnosed as M2 (according to the French-American-British classification) showing a t(8;21)(q22;q22) and a low NAP level as two markers of M2 cells. This is probably the first case of acute leukemia in which the cytogenetic analysis was performed before and after the appearance of a specific chromosome abnormality. PMID- 2253183 TI - Stepwise development of chromosomal abnormalities in angioimmunoblastic lymphadenopathy. AB - Cytogenetic studies of lymphoproliferative diseases, such as angioimmunoblastic lymphadenopathy (AILD), may provide a clue to the understanding of tumor development. Angioimmunoblastic lymphadenopathy may evolve from a nonmalignant lymphoproliferation into a peripheral T-cell lymphoma or even into a high-grade B cell lymphoma and thus offers the chance to observe cytogenetic changes during lymphoma development. We report the cytogenetic findings in 24 cases of AILD. They are discussed together with 18 previously published cases from the same series. A striking feature was that unrelated chromosome abnormalities, both clonal and nonclonal, were frequently observed. Eighteen of 25 cases with aberrant clones show trisomy 3 (a characteristic chromosome abnormality in peripheral T-cell lymphoma), trisomy 5, or both. This finding provides cytogenetic evidence that these cases are definitely peripheral T-cell lymphomas. From the results of the 42 cases, hypotheses of stepwise evolution of the chromosome abnormalities in AILD are deduced: the first step is the appearance of chromosome abnormalities in different cells because of a genetic instability. At this time, clonal proliferation of T cells was already demonstrated by the rearrangement of T-cell receptor genes. As a second step, chromosomally aberrant clones become established. A cytogenetically detectable monoclonal proliferation represents the third step. PMID- 2253184 TI - Absence of isochromosome 12p in a pineal region malignant germ cell tumor. AB - We report the first cytogenetic investigation of a rare pineal region mixed germ cell tumor. The mean modal number was 78. Multiple numerical and structural abnormalities were noted. Chromosomes 21 and 1q were consistently overrepresented, and chromosome 13 was underrepresented. A translocation involving chromosome 11 occurred in all metaphases examined. The Y chromosome was lost, and three copies of the X chromosome were present. No isochromosome 12p was identified, but four copies of chromosome 12 were present. PMID- 2253185 TI - Translocation (1;3)(p36;q21) in secondary leukemia. AB - A case of acute nonlymphocytic leukemia (M4) secondary to treatment for multiple myeloma is described. The patient presented a translocation t(1;3)(p36;q21) and monosomy 7. PMID- 2253186 TI - A complex chromosomal rearrangement and congenital anomalies in the progeny of a mother treated for childhood leukemia. PMID- 2253187 TI - i(12q) in B-cell chronic lymphocytic leukemia. PMID- 2253188 TI - T-cell acute lymphoblastic leukemia with t(1;18)(p36;q22). AB - An 8-year-old white boy with a T-cell acute lymphoblastic leukemia (T-ALL) developed chromosomal abnormalities t(1;18)(p36;q22) and del (6)(q21) at the first bone marrow relapse. Rearrangements of the chromosome region 1p36 have been reported previously in adults with T-ALL. PMID- 2253189 TI - Deletion of (7p13p14) in non-Hodgkin's lymphoma. AB - Deletion of the short arm of chromosome 7 at 7(p13p14) has been occasionally reported in non-Hodgkin's malignant lymphoma (NHL). The inclusion of this abnormality within the list of nonrandom changes awaited further data. We report three partial deletions of 7p with breakpoint at 7p13, found in various subtypes of NHL, and one deletion covering these bands (7p11 to 7p15). The association of 7p- with other chromosomal changes in the same NHL suggests that partial 7p deletion is a nonrandom secondary abnormality. PMID- 2253190 TI - Centromere separation. Early replication of repetitive DNA associated with inactive centromeres. AB - Four types of stable dicentric and one octacentric chromosomes from mouse brain tumor cells and L-929 cells were analyzed for the timing of replication of repetitive deoxyribonucleic acid (DNA) located in the centric and pericentric regions associated with active versus inactive centromeres. The repetitive DNA present in the heterochromatin blocks of inactive centromeres replicates much earlier than similar DNA associated with the active centromeres. The former appears to replicate during early to mid S when several euchromatic segments are still replicating. There seems to be little or no overlap in the timing of replication of the repetitive DNA present in the vicinity of prematurely separating centromeres (which are accessory and nonfunctional) and those that separate at meta-anaphase junction (which are the functional centromeres). In the absence of any information about the mechanism(s) controlling initiation and completion of DNA synthesis in the two types of heterochromatic blocks, the differential timing of replication of the DNA with similar base composition remains an enigma. PMID- 2253191 TI - Nonrandom chromosome abnormalities in testicular and ovarian germ cell tumor cell lines. AB - We report the karyotypic analysis of seven testicular and one ovarian germ cell tumor (GCT) cell lines, a number of which have previously been partially investigated. An i(12p) was found in each of the testicular GCT cell lines, while it was absent in the ovarian GCT cell line. Thus, our study extends to cell lines the observation from fresh tumor tissues that i(12p) is a highly nonrandom chromosomal abnormality of testicular GCT. Additional consistent nonrandom abnormalities in the testicular GCT cell lines included the following: del(1)(p22), del(1)(q21), i(1q), del(7)(q11.2), and del(12)(q14). The del(12)(q14) abnormality was identified in five of the cell lines investigated. This observation, together with previous detection of this marker chromosome in fresh tumor specimens by us and others, suggests that loss of genetic material on 12q may represent a primary change associated with malignant transformation of testicular germ cells. As reported in a previous study, a t(15;20)(p11;q11) translocation was identified in the ovarian GCT cell line. Interestingly, it also was seen in one testicular GCT cell line. In addition, a der(15)t(15;20)(p11;q11) marker chromosome was identified in two other testicular GCT cell lines. Thus, this reinvestigation of GCT cell lines has resolved the discrepancy regarding the occurrence of i(12p) in fresh tumors versus established cell lines and identified additional nonrandom abnormalities of potential importance to the development of GCTs. PMID- 2253192 TI - Cytogenetic features of erythroleukemia (EL). A study of 11 cases. AB - Cytogenetic studies were carried on 11 patients with erythroleukemia (EL). Most of these patients showed major chromosomal abnormalities (MAKA), karyotypic instability, and complex chromosomal rearrangements. On the basis of the cytogenetic criteria, 10 patients could be distinguished into erythroid (9 cases) and myeloid types of EL (1 case). The patients did not show any consistent chromosomal abnormality. However, abnormalities of chromosomes 1, 3, 7, 8, 16, and 17 were seen in more than one patient. In patients with the erythroid type of EL, besides the MAKA pattern, three patients showed increased frequency of hyperdiploid polyploid cells ranging from triploidy to tetraploidy. PMID- 2253193 TI - Trisomy 7 may be a primary change in noninvasive transitional cell carcinoma of the bladder. AB - We describe two cases of transitional cell carcinoma of the bladder associated with trisomy 7. In one of them, trisomy 7 was the only chromosome abnormality observed. In the second case, trisomy 7 was found in 25 (80.6%) of the metaphases; in two of them this was the only anomaly, while in three metaphases trisomy 8 was also present, and in other two trisomy 10 was also observed. Our results suggest that trisomy 7 could be a primary change in TCC, and a review of the literature indicates that when it is present as the sole karyotypic abnormality is may be associated with a non-invasive behavior of the tumor. PMID- 2253194 TI - Apparent correlation of sex chromosome loss and disease course in urothelial cancer. AB - In recent years, interest in the genetics of various solid tumours has increased dramatically. Over the last several years, our laboratory has pursued genetic studies of transitional cell carcinoma of the bladder. We have studied the cytogenetics and disease course of more than 100 patients, achieving successful cultures in more than 75%. In these patients, we observed the loss of a sex chromosome (either X or Y) with a frequency of 40%. We stratified patients with loss of sex chromosomes into three groups: 1) presence of markers or chromosome rearrangements, 2) aneuploidy without marker chromosomes, and 3) loss of a sex chromosome only. The relevancy of both the natural history and potential impact of sex chromosome loss to the disease course, including invasive potential, will be discussed in detail for each of the three groups. PMID- 2253195 TI - Glycosphingolipids of human gliomas. AB - Histologically characterized human gliomas of various grades of malignancy obtained during surgery were extracted, and their glycolipids were isolated and partially identified. Among the gliomas analyzed, three types of glycolipid component distribution could be identified. The glycosphingolipid (GSL) type I pattern correlated closely with that of the most malignant gliomas (Grade IV). Its neutral GSLs consisted of glucosyl- and, as a major component, dihexosylceramide, in addition to globo- and neolactotetraosylceramide. Galactosylceramide and sulfatide were absent. The gangliosides of GSL type I were almost exclusively of the GLac family, aside from small amounts of neolacto series-derived species. The neutral components of GSL type II were similar to those of GSL type I. The acidic compounds of GSL type II were gangliosides of the Gtri family and trace amounts of neolacto-series sialoglycolipids, in addition to GLac1 and GLac2. GSL type II contained no Gtet gangliosides and no sulfatide. The GSL type III pattern was that of the most benign gliomas, with all glycolipids present that are found in normal brain and, in addition, those of the GSL type II. PMID- 2253197 TI - Phase I and clinical pharmacology trial of 502U83 using a monthly single dose schedule. AB - 502U83 is an arylmethylaminopropanediol derivative exhibiting significant antineoplastic activity in a number of murine and human tumor models. In this Phase I trial, a 1-h or 4-h infusion of the agent was administered i.v. in 250 ml of 5% dextrose in water every 28 days. Fifty-three courses at doses of 25 to 2000 mg/m2 were administered to 36 patients with refractory solid tumors. Prolongation of the PR, QRS, and QT intervals on electrocardiograms was dose limiting at 2000 mg/m2. This prolongation appeared dose related and was reversible upon discontinuation of the infusion. No hematological toxicity was observed. Other toxicities included only sporadic and mild to moderate nausea and vomiting. No tumor responses were noted. 502U83 plasma concentrations were determined by high pressure liquid chromatography. Complete pharmacokinetic profiles were obtained for 21 of the 36 patients. After infusion, plasma concentrations declined in a biexponential or in a triexponential manner with a harmonic mean terminal t 1/2 of 8.83 h. Using a three-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 195 liters/m2 and 42.5 liters/h/m2, respectively, indicative of extensive tissue distribution. No correlation could be found between the pharmacokinetic parameters and prolongation of the cardiac conduction intervals. Because of the cardiac effects with the drug, the schedule of administration of 502U83 used in this study cannot be recommended. PMID- 2253196 TI - Phase I evaluation of a combination of monoclonal antibody R24 and interleukin 2 in patients with metastatic melanoma. AB - A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10(6) units/m2 i.v. over 6 h on days 1-5 and 8-12. R24 was given on days 8 12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 +/- 554/ml in patients treated at R24 doses of 8 and 12 mg/m2 versus 2239 +/- 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2 mediated T-cell activation in vivo. Two patients demonstrated increases in R24 mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro. PMID- 2253198 TI - A case-cohort study of diet and stomach cancer. AB - In this case-cohort study, from 1965 to 1968, 8006 Hawaiian men of Japanese ancestry were interviewed with a 24-h dietary recall questionnaire. After a follow-up period of 18 years, 111 stomach cancer incident cases were identified. Dietary data from these patients and from 361 cancer-free men were analyzed for intake of selected foods, food groups, and nutrients. We found that the consumption of all types of vegetables was protective against stomach cancer. Specifically, subjects in the highest group of vegetable consumption (greater than or equal to 80 g/day) had a relative risk of 0.6 (95% confidence interval, 0.3-0.9) in comparison with nonconsumers. This statistically significant inverse trend persisted after adjustment for age at examination and cigarette-smoking status. Similar but weaker protective effects from consumption of green and cruciferous vegetables were also observed. In addition, an inverse association between stomach cancer risk and intake of fruits was noted (P = 0.05), but this inverse trend was weakened after the effect of cigarette smoking was taken into account. There were no other dietary factors significantly associated with the risk of gastric cancer. PMID- 2253199 TI - Role of endocytosis in the action of ether lipids on WEHI-3B, HL60, and FDCP-mix A4 cells. AB - We investigated the effect of a number of platelet activating factor antagonists on cell killing by 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphoryl choline (ET 18-OCH3). Of six platelet activating factor antagonists tested, four were found to protect WEHI-3B leukemic cells against cell death induced by ET-18-OCH3. Certain other compounds, not platelet activating factor antagonists, had similar protective effects. The protective compounds were all lipophilic weak bases. We describe experiments that indicate that these compounds protect by inhibition of endocytic uptake of ET-18-OCH3. Sensitive cells showed rapid endocytic uptake, whereas in resistant cells, uptake was slow. Uptake of ET-18-OCH3 could be suppressed by inhibitors of endocytosis such as chloroquine, monensin, and vinblastine. We conclude that one of the principal determinants of sensitivity or resistance to ether lipids may be the rate at which cells take them up by endocytosis. PMID- 2253200 TI - Inherent sensitivity and induced resistance to chemotherapeutic drugs and irradiation in human cancer cell lines: relationship to mutation frequencies. AB - Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug resistant disease following chemotherapy. Cell lines derived from testis tumors retain hypersensitivity to both drugs and radiation in vitro, thus providing a model system with which to investigate the genetic basis of hypersensitivity to these agents. This study compared the spontaneous and both ethyl methanesulfonate and cisplatin-induced frequencies of mutation of 6-thioguanine resistance in 3 human bladder and 3 testis tumor cell lines and a bladder and a testis cell line with cisplatin resistance induced in vitro. The two tumor types showed similar frequencies of both spontaneous and induced mutation frequencies at this locus. Therefore, we failed to provide evidence for the hypothesis that the curability of testis tumors is associated with a low frequency of mutation to drug resistance. PMID- 2253201 TI - Pharmacokinetics in the rat of a panel of immunotoxins made with abrin A chain, ricin A chain, gelonin, and momordin. AB - A panel of immunotoxins was constructed by chemically attaching the ribosome inactivating proteins abrin A chain, ricin A chain, gelonin, and momordin to the monoclonal mouse IgG2a antibody Fib75 by means of a disulfide linkage. All the immunotoxins were toxic in tissue culture to the EJ human bladder carcinoma cell line expressing the antigen recognized by Fib75, inhibiting the incorporation of [3H]leucine by 50% at concentrations between 1 x 10(-10) M and 8 x 10(-10) M. The pharmacokinetics of the immunotoxins in the normal Wistar rat was determined following i.v. administration. The concentrations of intact immunotoxin in serum samples taken at various intervals after injection for up to 24 h were measured by solid-phase enzyme-linked immunosorbent assays specific for each of the four different ribosome-inactivating proteins. The Fib75 immunotoxins were cleared from the circulation with comparable, but not identical, biphasic kinetics best described by a two compartment open pharmacokinetic model. The alpha-phase half lives of the panel, between 0.35 and 0.71 h, were similar. The beta-phase half life of Fib75-abrin A chain, 13.3 h, was significantly longer than the beta-phase half-lives of Fib75-ricin A chain, Fib75-gelonin, and Fib75-momordin, between 7.5 and 8.6 h. Fib75-abrin A chain was found to be about 3- to 4-fold more resistant than the other immunotoxins to breakdown by reduction of the disulfide linkage between the A chain and the antibody with glutathione in vitro. This suggests that the longer serum half-life of Fib75-abrin A chain may have been due to greater stability against reduction in vivo. Analysis of serum samples obtained up to 24 h after injection of Fib75-abrin A chain revealed that the chemically intact immunotoxin present in the circulation retained full cytotoxic activity. An abrin A chain immunotoxin made with a different monoclonal mouse IgG2a antibody was also found to be more stable against reduction by glutathione in vitro than an analogous ricin A chain immunotoxin. Thus, abrin A chain may posses unique molecular properties that endow immunotoxins made with this A chain with greater stability in vivo than immunotoxins made with ricin A chain or other ribosome-inactivating proteins. PMID- 2253202 TI - Multiple membrane transport systems for the uptake of folate-based thymidylate synthase inhibitors. AB - N10-Propargyl-5,8-dideazafolic acid (CB3717) and 2-desamino-2-methyl-N10 propargyl-5,8-dideazafolic acid (ICI-198,583) are potent folate-based inhibitors of thymidylate synthase. We studied the membrane transport and the growth inhibitory effects of the two thymidylate synthase inhibitors on human CCRF-CEM leukemia cells with different transport properties for folic acid, reduced folates, and methotrexate (MTX). Membrane transport of [3H]ICI-198,583 can proceed via the high affinity/low capacity reduced folate carrier as supported by findings that (a) uptake of [3H]ICI-198,583 was significantly impaired in CEM cells which have a transport defect for MTX, (b) variants of CEM cells which overproduce the reduced folate carrier system showed a concomitant increase in the uptake of [3H]ICI-198,583 as for [3H]MTX, (c) MTX inhibited transport of [3H]ICI-198,583, and (d) uptake of [3H]ICI-198,583 was inhibited after treatment of CEM cells with an N-hydroxysuccinimide ester of MTX, which is a potent inhibitor of MTX transport. However, a membrane-associated folate-binding protein (FBP) offers another route for entry of CB3717 and ICI-198,583. CEM-FBP cells that have an elevated amount of FBP and do not have a functional reduced folate carrier were 640- and 61-fold more sensitive to CB3717 and ICI-198,583, respectively, compared to control CEM cells expressing the reduced folate/MTX carrier. This high sensitivity was related to a high affinity of the FBP for CB3717 and ICI-198,583 (Kd 2-3 nM), which is only 3-fold lower than for folic acid (Kd 1 nM) but significantly higher than for MTX (Kd 100 nM). Furthermore, after incubation of CEM-FBP cells for 24 h at 10 nM [3H]ICI-198,583, the high affinity binding of the FBP for ICI-198,583 allowed a 600-fold concentrative uptake of [3H]ICI-198,583 and its conversion to polyglutamate forms. These results indicate that multiple folate transport systems may be involved in the uptake of folate-based thymidylate synthase inhibitors. PMID- 2253203 TI - Appendectomy, appendicitis, and large bowel cancer. AB - A cohort of 167,561 persons who received multiphasic health checkups were followed up for cancer development. A history of appendectomy showed slightly negative nonsignificant associations with the development of cancer of the colon, rectum, and all sites combined. By inference, the relation of appendicitis with these cancers was also inverse. Upper 95% confidence limits were compatible only with small positive associations of appendectomy and appendicitis with these cancers. These data do not support the view that removing the appendix increases cancer risk by diminishing immunocompetency. A link between appendicitis and large bowel cancer has been noted in intersociety correlations and has been hypothesized to be due to prevention of both by a high-fiber diet. However, appendicitis does not appear to be a useful predictor of large bowel cancer within a developed society. PMID- 2253204 TI - Mechanisms of toxicity of hepsulfam in human tumor cell lines. AB - 1,7-Heptanediol disulfamate (hepsulfam, NSC 329680) is a new anti-cancer agent which is currently undergoing phase I clinical trials. The mechanism of action of this compound is not clear at this time. We have recently shown that hepsulfam was more toxic to L1210 leukemia cells than was busulfan. Consistent with the difference in toxicity, we found that hepsulfam induced DNA interstrand cross links in L1210 mouse leukemia cells, whereas busulfan did not. In the present study, we have found that hepsulfam was more cytotoxic to two human leukemia cell lines (HL-60 and K562) and to two human colon carcinoma cell lines (BE and HT-29) than was busulfan. As in L1210 cells, hepsulfam induced a higher level of DNA interstrand cross-links than busulfan. Both compounds induced DNA-protein cross links. Hepsulfam was also more cytotoxic to the human leukemia cell lines when the concentrations were reduced 10-fold and the duration of drug exposure was increased to 12-h This more accurately reflects the drug exposures that human leukemia cells may encounter in vivo. Under these 12-h drug exposures, hepsulfam was still able to form DNA interstrand and DNA-protein cross-links, whereas busulfan was only able to form DNA-protein cross-links. These results show that busulfan and hepsulfam react with DNA differently and that hepsulfam is a more potent cytotoxic agent. PMID- 2253205 TI - In vitro studies on the mechanism of action of hepsulfam in chronic myelogenous leukemia patients. AB - In the present study we have characterized the cytotoxicity and DNA damage induced by hepsulfam and busulfan in cells isolated from both chronic myelogenous leukemia (CML) patients and normal donors. hepsulfam inhibited colony-forming units-granulocyte, macrophage to a greater extent than busulfan in peripheral blood cells (PBCs) isolated from CML patients. Normal PBCs were equally sensitive to both agents and were more sensitive than the cells isolated from CML patients. Hepsulfam induced DNA interstrand cross-links in PBCs and bone marrow from both CML and normal volunteers, whereas busulfan produced few or no DNA interstrand cross-links. In addition, hepsulfam induced higher levels of DNA interstrand cross-linking than busulfam in three samples isolated from CML patients in blast crisis. Busulfan did however cause a small number of DNA strand breaks to be formed in human cells. Both agents produced similar levels of DNA-protein cross links in PBCs from CML patients. These results suggest that the mechanism of DNA reactivity of hepsulfam and busulfan differ and that hepsulfam may prove useful in the treatment of CML. PMID- 2253206 TI - Carcinogenic sulfide salts of nickel and cadmium induce H2O2 formation by human polymorphonuclear leukocytes. AB - Some derivatives of nickel, cadmium, and cobalt are carcinogenic in humans and/or animals but their mechanisms of action are not known. We show that they are capable of stimulating human polymorphonuclear leukocytes (PMNs), as measured by H2O2 formation, a known tumor promoter. Most effective were the carcinogens nickel subsulfide, which caused a 550% net increase in H2O2 over that formed by resting PMNs, followed by cadmium sulfide, 400%, and nickel disulfide, 200%. Nickel sulfide and cobalt sulfide caused statistically nonsignificant increases of 45 and 20%, respectively. Noncarcinogenic barium and manganese sulfides, and sulfates of nickel, cadmium, and cobalt were inactive. The enhancement of H2O2 formation by CdS and Ni3S2 (1 mumol/2.5 x 10(5) PMNs) was comparable to that mediated by the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate, used at 0.5 and 1 nM, respectively. Concurrent treatment of 12-O-tetradecanoylphorbol 13-acetate-stimulated PMNs with Ni3S2 or NiS caused a decrease in H2O2 accumulation from that expected if the effects were additive. Including catalase in the reaction mixture proved that the oxidant formed by stimulated PMNs was H2O2, whereas adding superoxide dismutase showed that superoxide was also present in PMN samples treated with NiS but not with Ni3S2. Since nickel- and cadmium containing particulates are deposited in the lungs and cause infiltration of PMNs, the ability to activate those cells and induce H2O2 formation may contribute to their carcinogenicity. PMID- 2253207 TI - Nuclear DNA content of altered hepatic foci in a rat liver carcinogenesis model. AB - In individual altered hepatic foci (AHF), aneuploidy occurs before malignant changes can be diagnosed histologically (O. Sudilovsky and T. K. Hei. Fed. Proc., 42:2225, 1983). In the current experiments Sprague-Dawley rats of both sexes were given i.p. injections of diethylnitrosamine (50 mg/kg body weight) 18 h after partial hepatectomy and were given a choline-sufficient diet (CS) for 1 wk. Four treatment groups were then formed and fed CS, CS containing 0.05% phenobarbital (PHB), choline-deficient diet (CD), and CD with 0.05% PHB. An extra female group received infusions of saline after the hepatectomy and fared CD. Control animals were partially hepatectomized, inoculated i.p. with saline, and placed on CS. The rats were sacrificed 16 wk later, liver sections were stained with a combined Feulgen-gamma-glutamyl transpeptidase stain, and the DNA content of gamma glutamyl transpeptidase-positive foci was measured cytospectrophotometrically. There were no AHF in the control animals. Hepatocytes from control livers and cells adjacent to foci in treated livers had peaks corresponding to the 2C, 4C, and 8C range. In AHF the ploidy, however, was predominantly diploid, tetraploid, or heterogeneous. The ratio of diploid to tetraploid cells in foci of rats provided with CS + PHB was 5.5 and in those supplied with CD + PHB was 0.09. This suggested that dietary manipulations change the nuclear DNA distribution of AHF. Aneuploidy was also present, as expected, in 4 of 33 AHF in the animals placed on CD + PHB. It was observed as well in 2 of 26 AHF of rats given CD but in none of the 20 AHF fed CS + PHB. These data indicate that CD (which acts as both initiator and promoter) may be responsible for the appearance of aneuploidy. A general model, based on these results and the clonality of each individual focus, is proposed for the development of cells through the preneoplastic stage. PMID- 2253208 TI - Persistent reduction of indigenous DNA modification (I-compound) levels in liver DNA from male Fischer rats fed choline-devoid diet and in DNA of resulting neoplasms. AB - Reduced levels of putative indigenous DNA modifications (I-compounds) in liver DNA of male Fischer 344 rats fed a hepatocarcinogenic choline-devoid (CD) diet for up to 7 mo have been previously reported. To investigate the persistence of this effect and possible relationships between I-compounds and hepatocarcinogenesis, liver DNA modifications of tumor-free male rats fed a CD diet for 3, 6, 9, or 12 mo, followed by a choline-supplemented (CS) diet to 16 mo, were compared with those in rats fed exclusively the CD or CS diet for 16 mo by a 32P-postlabeling assay. In addition, DNA from nontumorous and tumorous tissues of rats fed the CD diet similarly for 12 or 16 mo was analyzed. It was found that total I-compound levels in male rats consecutively fed CD and CS diets for various lengths of time were similar to those in rats fed the CD diet only and significantly lower than those in rats fed the CS diet only. I-compound levels of nontumorous regions from tumor-bearing livers were 73% of those in tumor-free livers from the same treatment group. I-compound levels were further reduced, some to undetectable levels, in tumor tissues and exhibited an inverse relationship with tumor incidence. The patterns and levels of I-compounds in liver DNA of CD diet-fed female rats, which were not susceptible to CD diet induced hepatocarcinogenesis, on the other hand, were not significantly different from those of controls. Thus, reduction of I-compound levels by feeding a CD diet lasted for many months after changing from the CD to the CS diet. Whether this persistent DNA alteration contributes to carcinogenesis remains to be determined. PMID- 2253209 TI - Effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine on blast progenitors of acute myeloblastic leukemia. AB - To determine the antileukemic effect of N4-behenoyl-1-beta-D arabinofuranosylcytosine (BH-AC), a synthetic masked compound of 1-beta-D arabinofuranosylcytosine, the pharmacokinetics and suppressive effect on leukemic blast progenitors of BH-AC were studied. When BH-AC was added to the suspension culture of leukemic cells, BH-AC gradually decreased in concentration in the culture media and was rapidly taken into the cellular fraction. The conversion from BH-AC to 1-beta-D-arabinofuranosylcytosine was noted in both the culture media and the cellular fraction. The concentration of 1-beta-D arabinofuranosylcytosine converted from BH-AC in the culture medium gradually increased during 7 days of culture, although the rate of conversion was variable among the samples. BH-AC suppressed primary and secondary blast colony formation in a dose responsive manner. BH-AC also suppressed the recovery of clonogenic cells in suspension culture. The suppression by BH-AC was more prominent in secondary blast colony formation and the recovery of clonogenic cells in suspension culture than in primary blast colony formation. Secondary blast colony formation and the recovery of clonogenic cells in suspension are considered to reflect the self-renewal of blast progenitors, while primary blast colony formation is considered to reflect the terminal divisions of blast progenitors. The results obtained in the present study suggest that BH-AC is more effective to suppress the self-renewal of blast progenitors than the terminal divisions. The findings offer a theoretical basis in the utility of BH-AC in the therapy of acute myeloblastic leukemia. PMID- 2253210 TI - Definition of a sequence, RYVVLPR, within laminin peptide F-9 that mediates metastatic fibrosarcoma cell adhesion and spreading. AB - A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic murine fibrosarcoma cell line, UV-2237-MM, adhered and spread on surfaces coated with laminin and peptide F-9 in a concentration- and time dependent fashion. Cells migrated toward laminin in Boyden microchemotaxis chambers but not toward peptide F-9. However, exogenous soluble peptide F-9 inhibited both the adhesion and migration of cells toward laminin. Polyclonal antibodies raised against peptide F-9 were capable of inhibiting laminin-mediated cell adhesion and migration. Peptide F-9 is located 265 residues from CDPGYIGSR, another sequence on the B1 chain of laminin which has been reported by others to promote cell adhesion (Graft et al., Cell, 48: 989-996, 1987). In contrast to peptide F-9, various control peptides including CDPGYIGSR did not promote the adhesion, spreading, or migration of the UV-2237-MM fibrosarcoma cells. In addition, neither exogenous peptide CDPGYIGSR nor antibodies raised against peptide CDPGYIGSR were capable of inhibiting laminin-mediated cell adhesion or migration. These results indicate that peptide F-9, but not peptide CDPGYIGSR, represents a major fibrosarcoma cell adhesion-promoting domain on intact laminin. A series of overlapping peptides were synthesized which contained various portions of the parent peptide F-9. The use of these peptides in cell adhesion assays demonstrated that the sequence RYVVLPR from the amino terminus of peptide F-9 was essential for cell adhesion-promoting activity. PMID- 2253211 TI - Effects of sex difference, gonadectomy, and estrogen on N-methyl-N-nitrosourea induced rat thyroid tumors. AB - The occurrence of thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet in Long-Evans (LE) rats was studied with special reference to sex difference, effect of gonadectomy, and estradiol administration. Rats of experimental groups 1-6 were given i.v. injections of 40 mg of MNU/kg of body weight at 50 days of age and fed on low iodine diet from 28 days of age to the end of the experiment (30 weeks after MNU administration). They consisted of male, female, castrated male, ovariectomized female, and gonadectomized male and female rats given 2.5 mg estradiol pellets s.c. Rats of groups 7-10 served as the respective controls without MNU or low iodine diet. Levels of serum thyroid stimulating hormone and estrogen receptor of the thyroid lesions were also examined. It was noted that the incidence of thyroid carcinoma was higher in females than in males (P less than 0.01) and did not change by castration in males but decreased in ovariectomized rats (P less than 0.01). Administration of estradiol after gonadectomy significantly increased the incidence of thyroid carcinomas in castrated and ovariectomized rats. Increase of mean serum thyroid stimulating hormone levels and thyroid and pituitary weights was also predominant in females. Mean thyroid stimulating hormone levels of both sexes were decreased by gonadectomy. Mean thyroid and pituitary weights were inhibited from increasing not by castration but by ovariectomy. Estradiol supplemented after gonadectomy significantly increased all of these factors. Estrogen receptors were detected in transplanted thyroid tumors but not in euthyroid tissues. The results suggest that estradiol promoted the thyroid tumorigenesis through activation of thyrotrophs in pituitary or direct interaction of estradiol and estrogen receptors in the thyroid. PMID- 2253212 TI - Expression of epithelial antigens Exo-1 and EPM-1 in human epidermal keratinocyte maturation and benign and malignant neoplasia. AB - Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM 1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis. PMID- 2253213 TI - An in vivo study of the role of the tumor cell cytoskeleton in tumor cell platelet-endothelial cell interactions. AB - We recently reported that disruption of tumor cell microfilaments or intermediate filaments resulted in an inhibition of the ability of tumor cells to induce the aggregation of homologous platelets in vitro (H. Chopra et al., Cancer Res., 48: 3787-3800, 1988). Previous investigators demonstrated that disruption of the tumor cell cytoskeleton decreases the ability of these cells to form lung colonies. We proposed that this latter effect is due, in part, to decreased interaction of tumor cells with platelets, following their arrest in the microvasculature. To test this hypothesis, B16 amelanotic melanoma cell microtubules, microfilaments, or vimentin intermediate filaments were disrupted with colchicine (50 microns), cytochalasin D (50 microns), or cycloheximide (50 microns), respectively, and then cells were tail vein injected into syngeneic mice. Both cytochalasin D- and cycloheximide-treated cells formed fewer lung colonies than did control cells. Colchicine, however, failed to inhibit lung colony formation. Neither colchicine nor cycloheximide treatment altered initial pulmonary arrest; however, fewer cycloheximide-treated cells remained in the lungs 8 h postinjection. Greater than 90% of control or colchicine-treated cells were found to be associated with activated platelets, and they also demonstrated typical cell membrane process formation 10 min and 8 h post-tumor cell injection. In contrast, less than 10% of cycloheximide-treated cells were in contact with activated platelets 10 min postinjection. However, by 8 h approximately 90% of cycloheximide-treated cells were in contact with activated platelets. This recovery coincided with the reformation of the B16 amelanotic melanoma vimentin intermediate filament network and the reacquisition of the ability to induce platelet aggregation in vitro. Neither colchicine nor cycloheximide treatment altered initial B16 amelanotic melanoma cell adhesion to murine microvessel derived endothelial cells. This study provides in vivo evidence in support of our previous findings that disruption of certain cytoskeletal elements (i.e., vimentin intermediate filaments) inhibits the tumor cell ability to activate platelets. This study also suggests that platelet activation may stabilize the initial tumor cell arrest in the microvasculature. PMID- 2253214 TI - Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. AB - Parathyroid hormone-related protein (PTHrP) is known to be a causative factor in humoral hypercalcemia of malignancy. A polyclonal rabbit antiserum directed against the amino-terminal region of the protein and immunoperoxidase methods have been used to locate the presence of PTHrP in a series of 102 consecutive invasive breast tumors removed surgically from normocalcemic women. Positive PTHrP staining was detected in 60% of the tumors but not in the accompanying normal breast tissue. Positive staining was related to the progesterone receptor status of the tumor (P = 0.039) and to the prognostic index of the patient (P = 0.046) and not to estrogen receptor status, patient age, tumor size, histological grade, or nodal status. PMID- 2253215 TI - p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. AB - Coordinate loss of one copy of the p53 gene and mutation of the remaining copy occur in colorectal carcinomas and in many other human malignancies. However, the prevalence of p53 gene mutations in carcinomas which maintain both parental copies of p53 has not previously been evaluated. Moreover, it is not known whether p53 gene mutations are limited to malignant tumors or whether they can also occur in benign neoplasms. To answer these questions, a total of 58 colorectal tumors have been examined; in each tumor, allelic losses were assessed using restriction fragment length polymorphisms and p53 gene mutations were assessed by sequencing cloned polymerase chain reaction products. The following conclusions emerged: (a) p53 gene mutations occurred but were relatively rare in adenomas, regardless of size and whether the adenomas were derived from patients with familial adenomatous polyposis; (b) In carcinomas as well as in adenomas, p53 gene mutations were infrequently observed in tumors which contain both copies of chromosome 17p (17% of 30 tumors), while tumors which lost one copy of chromosome 17p usually had a mutation in the remaining p53 allele (86% of 28 tumors); (c) p53 gene mutations were found at similar frequencies in primary tumor samples and in cell lines derived from tumors. These and other data suggest that the rate limiting step in p53 inactivation is point mutation and that once a mutation occurs, loss of the remaining wild-type allele rapidly follows. Both mutations and allelic losses generally occur near the transition from benign to malignant growth, and the p53 gene may play a causal role in this progression. PMID- 2253216 TI - The emerging biology of modern radiation oncology. PMID- 2253217 TI - Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors. AB - The new bioreductive drug 3-amino-1,2,4-benzotriazine 1,4-dioxide (SR 4233) shows a high selective cytotoxicity for hypoxic cells, both in vitro and in tumors in vivo. In the present experiments, we have tested the hypothesis that this selective killing of hypoxic cells might be exploited by taking advantage of the fluctuating hypoxia in tumors by use of a multidose regimen of SR 4233 with multiple small doses of X-rays. We have tested four different transplantable mouse tumors using a standard fractionated protocol of 8 x 2.5 Gy in 4 days, using a well tolerated dose of SR 4233 given with each radiation dose. All of the tumors showed a substantial enhancement of cell killing by SR 4233 over that produced by radiation alone with dose-modifying factors of 1.5 to 3.0 for the different tumors. In all four tumors, the enhancement of cell killing was greater than that produced by a large dose of the hypoxic cell sensitizer SR 2508 given before each irradiation, thereby demonstrating the superiority of the approach of using a hypoxic cytotoxic agent rather than a radiosensitizer in fractionated radiation protocols. The data suggest that SR 4233 has considerable promise as an adjunct to standard radiotherapy. PMID- 2253218 TI - Inhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice. AB - Immunotoxins are potent cell-killing agents that may be useful in the treatment of cancer. The early production of neutralizing antibodies to immunotoxins is one of the major limiting factors for their use in humans. 15-Deoxyspergualin (DSG), a derivative of spergualin, which is a metabolite of Bacillus laterosporus, has been found to have immunosuppressive activity in rodents, dogs, and primates. We examined the suppressive activity of DSG on the antibody response to Pseudomonas exotoxin in mice by enzyme-linked immunosorbent assay. Male BDF1 mice were immunized with a single dose of a nontoxic mutant of Pseudomonas exotoxin (40 micrograms) and then treated with i.p. injections of DSF at a dose of 10 mg/kg for 3 days. Although antibodies to Pseudomonas exotoxin were observed within 7 days in the control group, there was complete suppression of antibody production in the DSG-treated group. Immunosuppression has also been observed in animals immunized with multiple doses (10 mg x 7 d) of Pseudomonas exotoxin and treated with DSG at a dose of 5 mg/kg for 21 days. Similar immunosuppression was observed in mice given multiple doses of the immunotoxin, anti-Tac-LysPE40. We conclude that the immunosuppressive activity of DSG may be useful in increasing the duration of immunotoxin treatment. PMID- 2253219 TI - Purification and characterization of extracellular matrix-degrading metalloproteinase, matrin (pump-1), secreted from human rectal carcinoma cell line. AB - A metalloproteinase with Mr 29,000 was purified to homogeneity as a latent proenzyme from the conditioned medium of a human rectal carcinoma cell line CaR 1. This enzyme hydrolyzed casein more potently than gelatin embedded in polyacrylamide gels in zymography assay. Calcium ion was essential for the activity. It exerted the maximum activity at pH 7-9. Its activity was stimulated by organomercurials, such as p-amino-phenyl mercuric acetate and p-chloromercuric benzoic acid, and was inhibited by 1,10-phenanthroline but was hardly affected by diisopropyl fluorophosphate and pepstatin. When the purified proenzyme was activated by the organomercurials, it effectively hydrolyzed fibronectin, laminin, type IV basement membrane collagen, and several types of gelatins but not interstitial type I and III collagens. The treatment of the purified proenzyme with p-aminophenyl mercuric acetate or trypsin formed an active peptide with Mr 20,000. The structural analysis indicated that it was most likely identical to putative metalloproteinase-1, the complementary DNA of which had been cloned from human tumor mRNAs capable of hybridizing to a rat transin complementary DNA. Based on the fact that this enzyme is secreted extracellularly and degrades the matrix proteins, we propose the name "matrin" for this newly identified enzyme. PMID- 2253220 TI - Site-dependent differences in response of the UV-2237 murine fibrosarcoma to systemic therapy with adriamycin. AB - Murine fibrosarcoma UV-2237MM cells were implanted into different organs of syngeneic C3H/HeN mice. The resultant tumors were treated by i.v. administration of Adriamycin (ADR). Despite the high sensitivity of the fibrosarcoma cells to ADR in vitro, the established tumors growing in vivo exhibited marked differences in their responses to ADR. Tumors growing in the subcutis and the spleen were ADR sensitive, whereas lung metastases were not. The resistance of lung metastases to ADR was not due to selection of a drug-resistant population since tumor cells isolated from lung metastases were highly sensitive to ADR under in vitro conditions. The responsiveness of skin and spleen tumors to ADR was due neither to increased blood supply nor to preferential accumulation of ADR, since both parameters were higher in lung metastases. Protein kinase C activity levels correlated with ADR resistance in the closely related murine fibrosarcoma cell line UV-2237 and its ADR-selected multidrug-resistant variants. However, nearly identical levels of protein kinase C activity were found in UV-2237MM tumors growing in the lung, spleen, and subcutis, indicating that protein kinase C activity levels did not account for the different responses to ADR. The present studies suggest that the organ environment influences the response of UV-2237MM to ADR administered systemically. This finding may have implications for the design of animal models for therapy of disseminated cancer. PMID- 2253221 TI - Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. AB - We have probed for the presence of interleukin 6 (IL6) receptors in prostatic carcinoma cell lines (LNCaP, DU 145, and PC3) by examining their sensitivity to the cytotoxic effects of a chimeric toxin composed of IL6 and Pseudomonas exotoxin (PE). All three cell lines were killed by IL6-PE66(4)Glu, a version of IL6-PE in which the binding domain of native PE has been mutated to debilitate PE binding to its own receptor. This cytotoxic activity confirmed the presence of IL6 receptors on prostatic carcinoma cells. We have measured the number of IL6 receptors found on these cells and have further determined that they secrete IL6. These data provide evidence that IL6 and its receptor may play an important role in human prostate cancer. PMID- 2253222 TI - Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor positive tumors. AB - 16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha [123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha [123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers. PMID- 2253223 TI - Growth control of human mammary cancer cells (MCF-7 cells) in culture: effect of estradiol and growth factors in serum-containing medium. AB - The growth control of estrogen-dependent mammary cancer is very complex and only partly understood. The present study was undertaken in order to establish conditions for growth control of MCF-7 cells in monolayer culture with focus on the effect of estradiol-17 beta, fetal calf serum, and growth factors. The effect of charcoal-stripped fetal calf serum (CSFCS) on cell growth was dependent upon the presence of hormones or growth factors in the medium. In the presence of insulin (or insulin-like growth factor 1) and in the absence of estradiol-17 beta, increasing concentrations of CSFCS, 0.625-20%, produced a bell-shaped growth response curve. Serum concentrations greater than 2.5% inhibited cell growth in the absence of estradiol-17 beta, whereas CSFCS in a dose-dependent way up to 10% stimulated growth in the presence of estradiol-17 beta (5 x 10(-10) mol/liter). The growth inhibitory effect of CSFCS could not be demonstrated in the absence of insulin (or insulin-like growth factor 1) and estradiol-17 beta. CSFCS stimulated growth in a dose-dependent way in the presence of estradiol-17 beta and also in the absence of insulin. Both the putative growth inhibitor and stimulator were found to be heat stable and not dialyzable. Epidermal growth factor stimulated growth but was unable to eliminate the growth inhibitory effect of 5-10% CSFCS. Interleukin-1 alpha inhibited MCF-7 cell growth in a dose dependent way and produced a 75% reduction in cell number at a concentration of 5 x 10(-10) mol/liter. This inhibition was almost totally overcome by estradiol-17 beta. It is concluded that serum appears to contain factors with both stimulatory and inhibitory effects on the growth of MCF-7 cells. The inhibitory effect can be eliminated by estradiol (5 x 10(-10) mol/liter). In the presence of estradiol cell growth is stimulated by CSFCS in a dose-related way up to 5-10%. Taken together these data seem to indicate that estradiol stimulates cell growth in two principal ways: partly by eliminating the effect of an inhibitor, in support of a "negative hypothesis," and partly by an effect whereby estradiol permits a growth stimulator in CSFCS to be expressed, in support of the "indirect positive hypothesis." PMID- 2253224 TI - Heterogeneous protooncogene amplification correlates with tumor progression and presence of metastases in gastric cancer patients. AB - In order to evaluate the relevance of protooncogene alterations in gastric cancer and to specifically relate these alterations to types and stages of the neoplasia, we studied oncogenes of possible interest in gastric tumors with different clinical parameters. Fifty DNAs from primary gastric adenocarcinoma were analyzed, by the Southern blotting technique, for the presence of amplification or rearrangements of seven different protooncogenes: c-myc, c erbB2, c-Ki-ras, c-Ha-ras, c-N-ras, hst, and c-mos. All the tumors analyzed were histologically classified and staged. Amplification of the following genes was found: c-myc (2 of 50), hst (3 of 50), c-erbB2 (3 of 50), and c-Ki-ras (5 of 50). The simultaneous amplification of hst (3 cases), c-myc (1 of 3), or c-Ki-ras (2 of 3) was observed. Analysis of DNAs from atrophic and metaplastic gastric mucosa (which can be regarded as preneoplastic lesions) of the 10 patients showing gene amplification demonstrated that this was limited to neoplastic cells. Considering protooncogene amplification in general (i.e., involving different genes and occurring to different degrees) and clinical parameters of tumors, we found a statistically significant association between amplification and both tumor progression and presence of metastases. Therefore, at least for the genes analyzed, amplification is a relatively infrequent phenomenon and represents a late event in the temporal development of gastric cancer. PMID- 2253225 TI - Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts. AB - We previously showed that carcinogenic nickel, arsenic, and chromium(VI) compounds induced anchorage independence (AI) in diploid human fibroblastic cells (HFC) derived from foreskins (K. A. Biedermann and J. R. Landolph, Cancer Res., 47: 3815-3823, 1987). To elucidate the role of the valence state of chromium and solubility of chromium compounds in inducing AI, we studied the ability of soluble and insoluble hexavalent [chromium(VI)] and trivalent [chromium(III)] chromium compounds to induce mutation and AI in HFC. Chromium(VI) compounds (PbCrO4, CaCrO4, Na2CrO4, and CrO3) were 1000-fold more cytotoxic to HFC (average 50% lethal dose 0.5 microM) than chromium(III) compounds (CrCl3, Cr2O3, Cr2S3; average 50% lethal dose 500 microM). However, equal concentrations (0.1-10.0 microM) of soluble or insoluble chromium compounds in either +6 or +3 valence states induced similar increases in frequencies of AI in HFC (100-200/10(5]. Chromium(VI)- and chromium(III)-induced AI was a stable phenotype. All soluble chromium(VI) and insoluble chromium(III) compounds studied induced mutation to 6 thioguanine resistance at cytotoxic concentrations in HFC. Insoluble PbCr(VI)O4 and a soluble form of Cr(III)Cl3 were inactive in this assay. Mutation induction by chromium(III) compounds only occurred at cytotoxic concentrations (100-1000 microM) 1000-fold greater than those concentrations of chromium(VI) compounds (0.25-1 microM) which were cytotoxic, mutagenic, and induced AI. Soluble hexavalent Na2(51)CrO4 was taken up facilely by cells at concentrations that induced cytotoxicity, mutation, and AI. At concentrations of 0.25-1.0 microM, which induced AI but were not cytotoxic or mutagenic, or concentrations of 1-1000 microM, which were cytotoxic and mutagenic, soluble trivalent 51CrCl3 was not taken up by cells. An insoluble form of CrCl3 was not taken up intracellularly but did avidly associate with cells over the concentration range 1 to 100 microM which induced AI, cytotoxicity, and mutagenicity. Therefore, both chromium(VI) and chromium(III) compounds induced genotoxic effects in human fibroblasts. Cellular uptake, cytotoxicity, mutagenicity, and AI induced by soluble chromium(VI) compounds all occurred at the low concentrations of 0.2 to 1.0 microM; hence mutagenicity and induction of AI may be coupled for soluble chromium(VI) compounds but not for insoluble PbCrO4, which induced AI but was not mutagenic. Cytotoxicity and mutagenicity of insoluble chromium(III) occurred at concentrations of 10-100 microM, but induction of AI occurred at concentrations of 0.1-10 microM, indicating that inductions of mutagenicity and AI were not coupled for chromium(III) compounds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2253227 TI - Cytotoxicity of lonidamine alone and in combination with other drugs against murine RIF-1 and human HT1080 cells in vitro. AB - Lonidamine is an agent that is reported to inhibit recovery from potentially lethal damage. By itself, it has only mild anticancer activity. We have examined the ability of lonidamine to enhance the cytotoxicity of several drugs against a mouse and a human fibrosarcoma cell line in vitro. By itself, lonidamine showed only a limited cytotoxic effect with drug exposure up to 100 micrograms/ml and 24 h duration. Lower concentrations and shorter term exposures were not toxic to either of these tumor cell lines. When tested against the mouse line, the cytotoxicity of 5-fluorouracil, methotrexate, and etoposide was enhanced by lonidamine if the latter drug was given either before or after the exposure of the cells to the cytotoxic agents. For cisplatinum, bleomycin, mitomycin C, doxorubicin, and Actinomycin D, cytotoxicity was also enhanced, but only if lonidamine followed the other agents. In contrast, potentiation of 1,3-bis(2 chloroethyl)-1-nitrosourea toxicity was maximum when lonidamine preceded the nitrosourea. The human cells were more resistant to lonidamine and to the combination treatments than were the mouse cells. Nevertheless, substantial enhancement was seen particularly for cisplatin and mitomycin C. We examined in more detail the enhancement of cisplatin. Maximum interaction was obtained when lonidamine was given immediately following (or in conjunction with) the platinum agent. Our results suggest that lonidamine enhances the effects of several other agents in a time- and concentration-dependent manner and indicate a potential usefulness for lonidamine in multidrug therapy. PMID- 2253226 TI - Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinoma cells. AB - The effects of progesterone on the growth of breast carcinoma cells are undefined. In the present study we investigated the effect of progestins on insulin receptor gene expression and insulin action in human breast cancer cells. Treatment of T47D cells with the synthetic progestin R5020 induced a time- and dose-dependent increase in insulin receptor content as measured by both ligand binding studies and radioimmunoassay. Binding was half-maximally stimulated at 300 pM R5020 and maximal levels were reached after 4 days of treatment. Progesterone was 10-fold less potent than R5020. Cortisol had no effect on insulin receptor levels, while 17 beta-estradiol and dihydrotestosterone had minimal effects. Progestin treatment both increased insulin receptor mRNA levels and altered the relative distribution of the multiple insulin receptor mRNA transcripts. In order to study the functional significance of the increased insulin receptor levels, we incubated T47D cells with progesterone and then treated them with insulin. Insulin alone had a small effect on cell growth; however, the effect of insulin was markedly potentiated by progesterone treatment. These studies in breast cancer cells demonstrate, therefore, that insulin receptor gene expression is under the regulation of progestins and raise the possibility that progestin-insulin interactions may regulate breast cancer cell growth in vivo. PMID- 2253228 TI - Kinetics of the formation and removal of cisplatin-DNA adducts in blood cells and tumor tissue of cancer patients receiving chemotherapy: comparison with in vitro adduct formation. AB - During chemotherapy with a cisplatin-containing combination of drugs, 217 blood samples from 30 cancer patients were analyzed for the presence of the main cisplatin-DNA adduct cis-Pt(NH3)2d(pGpG) (Pt-GG). Cisplatin was administered during 3-h infusions on each of 5 consecutive days, resulting in increasing adduct levels which, on the average, were about twice as high after the fifth as after the first infusion. Higher levels were found in blood samples of patients who received the same total amount of cisplatin in one single 3-h infusion. No significant differences in adduct levels were found during first and repeated courses. The nonlinear dependence of adduct levels on total dose can be attributed to removal of adducts. At 21 h after a very first cisplatin infusion 76% of the adducts were removed. Lower percentages of removal were observed over the 21-h periods following the fourth and fifth infusions of 5-day courses (49 and 53%, respectively). After the initial 21 h the removal of adducts continued, albeit at a slower rate. Substantial interindividual variation was found in the adduct levels, which did correlate with the levels obtained after in vitro cisplatin treatment of blood samples from the same patients but not with their age or gender. Testicular cancer patients with complete tumor response showed higher adduct levels in their blood than those with partial response or progressive disease. When blood samples from 8 healthy volunteers were treated with cisplatin in vitro, the person-to-person variation in adduct levels and the intraindividual variation observed over a 2-year period were found to be in the same range, which was narrower than that observed with samples from treated patients. In vitro studies with human blood showed that the formation of the Pt GG adduct is proportional to cisplatin concentration and complete after about 1 hour. In some of the in vivo and in vitro cisplatin-treated blood samples, all 4 known platinum-DNA adducts were determined. In all cases Pt-GG was by far the major adduct, and no significant differences were observed with respect to the relative amounts of the 4 adducts. Similar adduct ratios were found in DNA from a testicular tumor obtained from a patient who underwent orchidectomy; the Pt-GG adduct level was about 10-fold higher than that in his blood cells. PMID- 2253229 TI - Myxoid liposarcoma with t(12;16) (q13;p11) contains site-specific differences in methylation patterns surrounding a zinc-finger gene mapped to the breakpoint region on chromosome 12. AB - The q13 to q15 region of human chromosome 12 is frequently and consistently rearranged in malignant and benign adipose tissue tumors as well as benign tumors of smooth muscle and salivary glands. A reciprocal translocation, (12;16) (q13;p11), is characteristic of the myxoid subtype of liposarcoma, whereas translocations within 12q13-14 are frequently observed in benign lipomas. We are using pulsed-field gel electrophoresis to study the 12q13-q14 region in order to detect and clone the respective translocation breakpoints in these tumors. The locus GLI, which encodes a zinc-finger protein, has been mapped to the same region as the myxoid liposarcoma breakpoint. Pulsed-field analysis of myxoid liposarcoma and lipoma DNA has allowed us to construct a 600-kilobase physical map surrounding the GLI locus, which shows that breakpoints in both types of tumor are outside this region. However, myxoid liposarcoma DNA samples contained altered restriction fragments detectable with GLI probes that were highly specific and reproducible from case to case. These altered fragments are due to highly specific and reproducible methylation differences that are unique to myxoid liposarcoma DNA. These methylation changes may prove to be useful clinically as a diagnostic tool to differentiate subtypes of liposarcoma. PMID- 2253230 TI - Expression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells. AB - DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated with their transferase activity levels, whereas Mer- cells contained undetectable amounts of transferase mRNA. The mRNA levels were not induced in human cells by treatments that induce other DNA damage-inducible genes. These results demonstrate that in human cells the transferase gene is constitutively expressed, that its expression is related to activity levels, and that in Mer- tumor cells the expression of the transferase gene is probably blocked at the level of mRNA production. PMID- 2253231 TI - DNA in situ sensitivity to denaturation in bladder cancer and its correlation with tumor stage. AB - DNA content and sensitivity of DNA in situ to denaturation by acid were analyzed by flow cytometry of cell nuclei freshly isolated from the bladder tumors of 32 patients and were compared with normal urothelium of 8 subjects. DNA sensitivity to denaturation was assessed in RNase treated cells by acridine orange metachromasia following partial denaturation with hydrochloric acid; the extent of denatured DNA is given as an index (alpha t), representing the ratio of single stranded to total DNA per nucleus. Of the low stage tumors (papillomas, Ta, Tis, T1) 11 of 18 (61%) were aneuploid. Of the high stage tumors (T2 and T3a) 11 of 14 (79%) were aneuploid. DNA in nuclei of normal transitional epithelium was very sensitive to denaturation, as was papilloma, characterized by nuclear alpha t indices of 0.73 +/- 0.01 (SD) and 0.73 +/- 0.04, respectively. Nuclear DNA of noninvasive carcinomas (Ta, Tis) was significantly more resistant to denaturation (alpha t = 0.69), and DNA of invasive carcinomas was most resistant, ranging from alpha t = 0.61 (T1 tumors) to alpha t = 0.59 (T2 tumors) to alpha t = 0.57 (T3 tumors). High stage tumors as a group (T2, T3) had significantly different (lower) alpha t values than low stage tumors (Ta, Tis, T1). In model cell culture systems it is known that a decrease in alpha t index, i.e., greater resistance to denaturability, occurs as cells transit from resting phase into the cell cycle. Whether the alpha t index can be used to estimate resting vesus cycling cells of human tumors is still speculative; changes in DNA denaturability also are known to occur with changes in chromatin structure during cell differentiation and in transformation. However, the empirical relationship between alpha t index and tumor stage, of itself, may prove clinically useful in identifying more advanced and perhaps more aggressive tumors. PMID- 2253232 TI - Pharmacokinetics and metabolism of cyclopentenyl cytosine in nonhuman primates. AB - The plasma and cerebrospinal fluid pharmacokinetics of cyclopentenyl cytosine (CPE-C) were studied following i.v. bolus and continuous i.v. infusion in male rhesus monkeys. Following an i.v. bolus dose of 100 mg/m2 plasma elimination of CPE-C was biexponential with a mean t1/2 alpha of 8.4 min, a mean t1/2 beta of 36 min, and a total clearance (CLTB) of 662 ml/min/m2, which is 5- to 10-fold higher than clearance rates in rodents and dogs. Less than 20% of the total dose of CPE C was excreted unchanged in the urine. The remainder was excreted as the inactive deamination product cyclopentenyl uridine (CPE-U). The ratio of the areas under the plasma concentration versus time curves of CPE-U to CPE-C was 7.0 +/- 2.4 following i.v. bolus CPE-C. The cerebrospinal fluid:plasma ratios of CPE-C and CPE-U were 0.08 and 0.30, respectively. Continuous i.v. infusion of CPE-C was compared to continuous infusion of 1-beta-D-arabinofuranosylcytosine in two monkeys. Steady state plasma concentrations, normalized to a dose of 12.5 mg/m2/h of CPE-C and an equimolar dose of 1-beta-D-arabinofuranosylcytosine, were 2.1 and 0.53 microM, respectively. The steady state concentrations of their corresponding uridine metabolites (CPE-U and 1-beta-D-arabinofuranosyluridine) were 8.2 and 15.5 microM. The rapid elimination of CPE-C by deamination in the primate resulted in a much higher CLTB and considerably lower total drug exposure than in rodents and dogs that clear CPE-C at a much lower rate by renal excretion. These significant interspecies differences in the disposition of CPE-C should be considered in the selection of a starting dose and schedule for human trials and suggest that a pharmacologically directed dose escalation scheme should be used in the planned phase I studies. PMID- 2253233 TI - Systemic alkalinization inhibits the ability of flavone acetic acid to augment natural killer activity, induce cytokine gene expression, and synergize with interleukin 2 for the treatment of murine renal cancer. AB - Flavone acetic acid (FAA) is an investigational drug that augments natural killer activity, induces the genes for alpha- and gamma-interferon (IFN) and tumor necrosis factor alpha, and synergizes with recombinant interleukin 2 for the successful treatment of murine renal cancer. However, in most clinical studies of FAA only minimal immunomodulatory effects have been reported. Most of the patients in these studies have also been given sodium bicarbonate to prevent possible nephrotoxicity. The current study was performed to determine whether alkalinization had any effects on FAA-induced immune modulation and therapeutic activity in mice. The results showed that alkalinization inhibited the treatment of murine renal cancer by FAA plus recombinant interleukin 2 such that the survival rate of 84% in nonalkalinized mice was reduced to 0 in mice that were alkalinized during treatment. Alkalinization also significantly inhibited the ability of FAA to augment both splenic and hepatic natural killer activity in a dose-dependent manner. In contrast, alkalinization did not inhibit the ability of polyinosinic:polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose, maleic anhydride divinyl ether, or Propionibacterium acnes to augment liver-associated natural killer activity. By Northern blot analysis, it was shown that the induction of mRNA for IFN-alpha, IFN-gamma, and tumor necrosis factor alpha by FAA in the spleen cells of mice was significantly reduced in alkalinized mice. Consistent with a reduction in the FAA-induced expression of the cytokine genes, alkalinization also resulted in a significant decrease in both the peak serum concentration and duration of detectable IFN activity following FAA treatment. Increasing the dose of FAA in alkalinized mice to 300 mg/kg overcame the deleterious effects of alkalinization for treatment of murine renal cancer by FAA plus recombinant interleukin 2. These results demonstrate that the process of alkalinization inhibits the immunomodulatory and immunotherapeutic effects of FAA in mice and suggest that alkalinization might have similar deleterious effects on FAA-induced immune stimulation in human clinical trials. PMID- 2253234 TI - Epidermal growth factor inhibits transiently the progression from G2-phase to mitosis: a receptor-mediated phenomenon in various cells. AB - An immediate effect of epidermal growth factor (EGF) on the cell cycle is described. EGF, when given to replicating cells such as HeLa, A431, and D HER 14, very rapidly inhibits the transition from G2 phase to mitosis (M) in a transient fashion. The influence of EGF (10(-10) to 10(-7) M concentrations) on the G2-M transition of individual cells has been analyzed by time-lapse photography in cell lines carrying intact, mutated, or no EGF receptor. The G2-M transition of cells devoid of EGF receptor or carrying an EGF receptor devoid of most of the cytoplasmic domain was not influenced by EGF. In cells carrying intact EGF receptor, EGF caused a transient and dose-dependent delay in G2 phase which could last for greater than 2 h. Cells were inhibited in G2 within less than 10-20 min prior to prophase. A parasynchronous recovery from G2 inhibition was observed at large EGF concentrations; the G2-M transition rate exceeded that of the controls. The system described may represent a model for the mechanistic analysis of a ligand-induced transient restriction of the cell cycle, particularly at the G2-M border. PMID- 2253235 TI - Epithelial cell kinetics in the remaining colorectal mucosa after surgery for cancer of the large bowel. AB - We used microautoradiography in order to evaluate cell replication of the remaining colorectal mucosa in 20 patients previously operated on for cancer of the large bowel. The results were compared to those of 24 controls without neoplasms or other relevant colorectal disease. Samples of colorectal mucosa were taken during endoscopy. At histological examination each labeled intestinal hemicrypt was divided into 5 longitudinal compartments, from the base to the surface, and S-phase cells in each compartment were counted. Total labeling index (LI, ratio of labeled to total cells x 100) and labeling index per crypt compartment were similar in surgical patients and in controls. In contrast, both total LI and labeling index in the upper portions of the crypt (compartments 3, 4, and 5) were significantly higher in the 9 patients who showed recurrence of polyps than in those (n = 11) without recurrence. The LI in compartments 4 and 5 (the "high crypt region") was 4.37 +/- 0.95 (SEM) in patients with recurrence versus 0.88 +/- 0.21 (P less than 0.001) in patients with negative endoscopy finding and 1.47 +/- 0.22 in controls. Moreover, the fifth compartment was labeled in 8 of 9 individuals in whom polyps recurred but in only 2 of 11 patients without recurrence and 3 of 24 controls. In conclusion, after resection for large bowel cancer colonic epithelial cell proliferation tends to become more quiescent and similar to that of controls. However, in the subgroup of patients in whom polyps reappear, the colorectal mucosa maintains a hyperproliferative state with an expansion of the replicative zone to the most superficial portions of the crypt. These findings support the sequence adenoma-carcinoma and suggest that the evaluation of cell proliferation might be useful in the identification of subjects at increased risk for multiple tumors of the large bowel. PMID- 2253236 TI - Purification of hepatic polymorphic arylamine N-acetyltransferase from homozygous rapid acetylator inbred hamster: identity with polymorphic N-hydroxyarylamine-O acetyltransferase. AB - The polymorphic acetyltransferase isozyme expressed in homozygous rapid acetylator inbred hamster liver cytosol was purified over 2000-fold by sequential Q-Sepharose fast-flow anion-exchange chromatography, Sephacryl S-200 high resolution size-exclusion chromatography, Mono Q anion-exchange fast-protein liquid chromatography, and preparative polyacrylamide gel electrophoresis. The isozyme migrated as a single homogeneous monomer following both preparative and sodium dodecyl sulfate-polyacrylamide electrophoresis. The molecular weight was estimated at 34,170 following elution via size-exclusion chromatography and 35,467 following migration via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The homogeneous polymorphic acetyltransferase exhibited a broad substrate specificity; it catalyzed the acetyl coenzyme A-dependent N-acetylation of p-aminobenzoic acid, carbocyclic arylamine carcinogens such as 2 aminofluorene, 4-aminobiphenyl and beta-naphthylamine, and heterocyclic arylamine carcinogens such as 2-aminodipyrido[1,2-a:3'2'd]imidazole and 3-amino-1-methyl-5H pyrido[4,3-b]indole. It also readily catalyzed the acetyl coenzyme A-dependent metabolic activation (via O-acetylation) of N-hydroxy-2-aminofluorene to DNA adducts but not the metabolic activation (via intramolecular, N,O-acetyltransfer) of N-hydroxy-2-acetylaminofluorene or N-hydroxy-4-acetylaminobiphenyl to DNA adducts. Conversely, the partially purified monomorphic acetyltransferase isozyme from the same hamsters readily catalyzed the metabolic activation of N-hydroxy-2 acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl, and rates of metabolic activation of these substrates did not differ between homozygous rapid and slow acetylator liver, intestine, kidney, and lung cytosols. Heat inactivation rates for the purified polymorphic acetyltransferase isozyme were first order and indistinguishable for the acetyl coenzyme A-dependent N-acetylation and O acetylation activities. The results strongly suggest the expression of a single polymorphic acetyltransferase product of the hamster polymorphic acetyltransferase gene that catalyzes both acetyl coenzyme A-dependent N acetylation and O-acetylation of arylamine and N-hydroxyarylamine carcinogens but not the metabolic activation of N-hydroxy-N-acetylarylamines (arylhydroxamic acids) via intramolecular N,O-acetyltransfer. Consequently, acetylator genotype dependent metabolic activation of N-hydroxyarylamines to a DNA adduct in hamster is catalyzed by direct O-acetylation of the hydroxyl group and not via sequential N-acetylation followed by N,O-acetyltransfer. PMID- 2253237 TI - Frequency and structure of p53 rearrangements in human osteosarcoma. AB - Osteosarcoma is the most frequent childhood bone cancer (Tebbi, C. K., and Gaeta, J. Pediatr. Ann., 17:285-300, 1988). Using Southern blot mapping, we found that 11 of 60 (18%) osteosarcomas had altered restriction patterns of the p53 gene and that six of these had loss of the other p53 allele. In contrast, no alteration of the p53 gene was detected in 50 samples from other types of sarcomas. Fifty % of osteosarcoma cell lines (4 of 8) also had gross rearrangements of one p53 allele with loss of the second allele, and these had no detectable p53 mRNA. Osteosarcoma cell lines with no detectable alteration of the p53 gene contained abundant p53 transcripts. Taken together, data show that human osteosarcomas can have rearrangements of the p53 gene; these rearrangements may cause loss of normal constraints on cellular growth. PMID- 2253238 TI - Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice. AB - Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU 10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re (3.7-day physical half-life; 1.07-MeV beta particle and 137-keV gamma, 9% abundance) by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 (5.3% injected dose/g) at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained. The biodistribution, pharmacokinetic, and scintigraphic image results suggest that 186Re-labeled NR-LU-10 shows promise as a therapeutic agent for gastrointestinal cancer. PMID- 2253240 TI - Glucocorticoid receptor monoclonal antibodies define the biological action of RU 38486 in intact B16 melanoma cells. AB - The mechanism of action of the synthetic glucocorticoid antagonist, RU 38486, has yet to be completely elucidated. Although RU 38486 is a potent antiglucocorticoid in vivo, several studies have indicated that it has some agonist activities in vitro, such as high-affinity steroid binding to the receptor, activation, and DNA binding. Nevertheless, these in vitro postbinding events do not lead to any known gene expression. To understand the action of the glucocorticoid antagonist RU 38486, we studied glucocorticoid receptor localization on a mouse melanoma cell line (B16C3) by indirect immunofluorescent staining techniques, using monoclonal antibodies to the glucocorticoid receptor. Our data in intact cells suggest that, unlike glucocorticoid agonists such as triamcinolone acetonide, and similar to the glucocorticoid antagonist cortexolone, RU 38486-bound receptors do not translocate to the nucleus and hence do not allow for transcription of glucocorticoid-regulated genes to occur. Passage through the nuclear membrane may be a rate-limiting step in the action of glucocorticoid antagonists, and translocation may in itself be an important regulatory mechanism of steroid hormone action. PMID- 2253239 TI - Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni cancer syndrome: aneuploidy and immortalization. AB - Families of patients with the Li-Fraumeni cancer syndrome have an inherited pattern of sarcomas and various other types of cancers that follow a dominant mode of transmission, an early age of onset, and exhibit multiple primary tumors. As soft tissue sarcomas (including fibrosarcomas) are frequently observed with this syndrome, the in vitro growth characteristics of fibroblasts derived from skin biopsies of Li-Fraumeni syndrome patients were studied. Control fibroblasts maintained a normal morphology and eventually senesced in culture. Fibroblasts from seven of eight affected individuals developed changes in morphology, anchorage-independent growth, and chromosomal abnormalities. In a fashion similar to that of fibroblasts from normal donors they underwent a growth crisis during which their growth was slow, but they continued to grow past the point at which control samples had stopped dividing (35 population doublings). Fibroblasts from Li-Fraumeni cancer patients escape senescence, growing well beyond 35 population doublings with growth rates similar to early-passage cells. Patient fibroblasts maintain the morphology of a transformed cell but remain nontumorigenic in nude mice. These observations of the behavior of fibroblasts from patients with the Li Fraumeni syndrome may have predictive value for the determination of gene carriers within these families who are at high risk of cancer. PMID- 2253241 TI - Mutagenesis of mouse intestine in vivo using the Dlb-1 specific locus test: studies with 1,2-dimethylhydrazine, dimethylnitrosamine, and the dietary mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. AB - The ability of three model carcinogens, 1,2-dimethylhydrazine, dimethylnitrosamine, and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, to induce mutation in a novel in vivo assay in mouse intestine has been examined. The assay is based on mutations at the Dlb-1 locus which determines the tissue specific pattern of expressio of the binding site for the lectin Dolichos biflorus agglutinin. In C57BL/6J x SWR F1 mice Dlb-1 mutants are recognized as clones of epithelial cells not staining with a peroxidase conjugate of D. biflorus agglutinin. Chronic administration of 1,2-dimethylhydrazine (20 mg/kg/week s.c. for 10 weeks) induced Dlb-1 mutants, whereas administration of a single dose did not. Similarly, chronic dimethylnitrosamine treatment p.o. (0.001% in drinking water for 8 weeks) induced Dlb-1 mutants, but acute administration did not. In contrast, neither chronic nor acute treatment of the mice with 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline induced Dlb-1 mutations. The activities of 1,2 dimethylhydrazine, dimethylnitrosamine, and 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline in the Dlb-1 assay more accurately reflect their carcinogenic potential than do many in vitro bioassays. PMID- 2253242 TI - Suppression of wound healing in tumor bearing animals as a model for tumor-host interaction: mechanism of suppression. AB - Tumor wound healing was explored as a possible model for tumor-host interactions. Wound healing within tumors progressed normally through the hemorrhagic and inflammatory stages but failed at the mesenchymal ingrowth phase. Due to this failure of mesenchymal ingrowth, no significant collagen deposition could be detected within tumor wounds. Fluid collected from tumor wounds markedly altered fibroblast cytoskeletal structures and profoundly inhibited fibroblast proliferation and collagen synthesis. This suppression did not appear to be the direct consequence of tumor products, since tumor conditioned media enhanced fibroblast proliferation and had no effects on collagen synthesis and fibroblast cytoskeleton. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of lysed fibroblasts demonstrated that two polypeptides (Mr 280,000 and 240,000) were induced in or adherent to fibroblasts exposed to fluid from the tumor wound but not in fibroblasts exposed to fluid obtained from wounds in normal tissue or tumor conditioned media. These findings suggest that tumor wound healing is a model for mesenchymal inhibition within tumors but that the inhibitors are not tumor derived products. PMID- 2253243 TI - Interaction of fibrinogen with murine melanoma cells: covalent association with cell membranes and protection against recognition by lymphokine-activated killer cells. AB - B16/F10 melanoma cells, in a medium containing fibrinogen, form a coating of fibrin(ogen) on their surfaces. This coating is cross-linked in a manner characteristic of catalysis by cellular transglutaminase. The fibrin(ogen) coating on the surface of these tumor cells provides protection against the lytic effect of autologous lymphokine-activated killer cells. PMID- 2253245 TI - Renal artery injury in child abuse. AB - Injuries constitute one of the major disease categories in infancy and childhood. Child abuse is a significant portion of this. A rare case of battered child presenting with acute renal artery occlusion is reviewed. PMID- 2253244 TI - Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. AB - Both permanent cultured cell lines and athymic mouse xenografts were established from two human glioblastomas. Biopsies from D-245 MG and D-270 MG contained amplified and rearranged epidermal growth factor receptor (EGFR) genes. Although the gene amplification and rearrangement seen originally was maintained in the xenografts, cultured cell lines established from these biopsies lost the amplified rearranged genes in vitro. Analysis of these cell lines and 11 additional permanent human glioma cell lines with normal EGFR gene copy number showed from 2.7 x 10(3) to 4.1 x 10(5) high affinity EGFRs/cell by radioreceptor assay. The RNase A protection assay showed minimal differences in the quantity of EGFR mRNA among the 13 glioma lines, while the D-245 MG and D-270 MG xenografts expressed approximately 10-20 times as much EGFR mRNA as the corresponding cell lines. Immunoprecipitation of EGFR from these lines, including D-245 MG and D-270 MG, demonstrated only the intact Mr 170,000 Da form, while truncated Mr 145,000 Da and 100,000 Da EGFR proteins were immunoprecipitated from the D-270 MG and D 245 MG xenografts, respectively. These studies demonstrate that gliomas with amplification of the EGFR gene are capable of establishing in culture but that the amplified rearranged genes are not maintained. Possible explanations are that the abnormal genes are lost during serial passage or that the cells with amplified rearranged genes only represent a minor subpopulation of cells, which are unable to grow in culture. In either case, these observations suggest that high expression and structural abnormalities of EGFR proteins generated by amplification and rearrangement of the EGFR gene provide a growth advantage for gliomas in vivo but not in vitro. PMID- 2253246 TI - Renal transplantation in a child with primary oxalosis. AB - Primary hyperoxaluria (oxalosis) is an autosomal recessive disorder due to an inherited deficiency of the peroxisomal alanine:glyoxylate aminotransferase characterized by increased production and urinary excretion of oxalate and glycolate resulting in renal failure due to oxalate deposition. Because of the risk of continuing oxalate deposition in the transplanted kidney, oxalosis had been considered a contraindication for transplantation. A 5-year-old boy with oxalosis, maintained on peritoneal dialysis, received a haploidentical qiving related transplant. The preoperative management included donor-specific transfusions and daily hemodialysis to remove a maximum amount of oxalate. The immunosuppression consisted of azathioprine and prednisone. Aggressive fluid management including noncalciuric diuretics (hydrochlorothiazide) kept urine output high. Pyridoxine, magnesium, neutral phosphate and sodium benzoate were used to prevent deposition of oxalate in the transplanted kidney. Two acute rejection episodes responded to steroid boluses. A kidney biopsy during the second rejection episode confirmed the diagnosis but also revealed oxalate deposits in the transplanted kidney. More than 4 years after transplantation, the patient has catch-up growth and his serum creatinine is 1.4 mg/dl. In conclusion, oxalosis is not an absolute contraindication to renal transplantation. Transplantation can be performed successfully utilizing living-related donor kidneys and aggressive medical management. The risks of deterioration of function and oxalate deposition in the transplant kidney are offset by improvement in quality of life. PMID- 2253248 TI - Focal sclerosing glomerulonephritis in a child with Laurence-Moon-Biedl syndrome. AB - We report a 6-year-old white male with Laurence-Moon-Biedl syndrome and focal sclerosing glomerulonephritis (FSGN). To our knowledge, FSGN has not been reported previously in patients with this syndrome. We wish to alert the clinician to the wide variety of renal abnormalities that can be seen in patients with this rare, autosomal recessive disorder. PMID- 2253249 TI - Acute poststreptococcal glomerulonephritis and acute rheumatic fever: occurrence in the same patient. AB - Group A streptococcus can cause both acute glomerulonephritis and acute rheumatic fever. The occurrence of characteristic acute poststreptococcal glomerulonephritis and acute rheumatic fever in the same patient is rare. We describe a 10-year-old girl with acute rheumatic fever who presented with the typical clinical and biopsy findings of acute poststreptococcal glomerulonephritis. PMID- 2253247 TI - Early and unusual presentation of type I primary hyperoxaluria. AB - Oxalosis, the systemic deposition of calcium oxalate crystals, may occur in several hyperoxaluric states due to increased production or absorption of oxalate. Type I primary hyperoxaluria (PH I) is a rare autosomal recessive disease caused by deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase. Most patients with this disorder are noticed in mid-childhood or even later due to symptoms related to urinary stone disease. In this paper, we report a patient with PH I with a rapid downhill progression to renal failure and death. Oxalosis was detected by renal biopsy, and the diagnosis of PH I was confirmed by increased urinary oxalate and glycolate levels. PMID- 2253250 TI - Familial hyperuricemia and renal insufficiency. AB - A kindred is described in which hyperuricemia and renal insufficiency were observed in three generations. The hyperuricemia appeared to precede the renal diseases. Lowering the serum uric acid level to normal did not decrease the progression of renal insufficiency. This suggested that the hyperuricemia was a marker of a familial nephropathy and possibly not the cause. PMID- 2253251 TI - External iliac vessel tear presenting as acute anuria. AB - The unusual occurrence of acute anuria due to external iliac vessel tear is described. Immediate accurate diagnosis helped to prevent unnecessary procedures in a child. PMID- 2253252 TI - The immune system in uremia. PMID- 2253253 TI - Mumps associated with nephritis. AB - During an endemic of mumps in 1987, urinalysis was performed in 124 children with the symptoms of mumps during the acute phase of the disease, 36 children (29.0%) with microscopic hematuria and 8 children (6.4%) with proteinuria were studied. In the children with abnormal urinalysis, whose creatinine clearance was within the normal range, an urine culture for mumps virus was also performed. Nine specimens (20.4%) were positive, 8 (88.8%) of them during the first 5 days of illness. Renal biopsy, performed in a girl with persistent hematuria, revealed a mild mesangial proliferative glomerulonephritis with deposition of immunoglobulins A and M, C3, and mumps virus antigen in the glomerulus, suggesting an immune complex deposition. Electron microscopy demonstrated a moderate number of granular electron-dense deposits in the paramesangial regions. The relationship between the development of mumps and the onset of nephritis and the immunofluorescent demonstration of mumps antigen in the glomeruli suggested that the mesangial nephropathy may have developed after the mumps infection. Therefore, in our cases, the clinical course was benign. PMID- 2253255 TI - Decreased urinary citrate in premature infants with lung disease. AB - Urinary citrate prevents nephrocalcinosis in adults. Premature infants have a high incidence of nephrocalcinosis. We measured urinary citrate (Ucit) and creatinine (Ucre) concentrations in infants with and without lung disease. Ucit was lower in the infants requiring mechanical ventilation than in the controls (mean = 9.7 vs. 15, p = 0.05). Ucit/Ucre ratios were lower in hypercarbic (mean = 0.95 vs. 1.47 in normocarbic, p less than 0.05) and acidotic (mean = 0.57 vs. 1.44 in nonacidotic, p less than 0.004) premature infants. The lowered Ucit of premature infants with lung disease (and acidosis or hypercarbia) may predispose to nephrocalcinosis by increased urinary lithogenesis. PMID- 2253254 TI - Plasma and urinary growth hormone and insulin-like growth factor I in children with chronic renal insufficiency. AB - We investigated the plasma and urinary growth hormone (GH) levels, and plasma insulin-like growth factor (IGF-I) in 15 (8 prepubertal and 7 pubertal) subjects with chronic renal insufficiency. Four of our 7 pubertal patients had a short stature (standard deviation score from -2.7 to -4.0). Significantly increased plasma GH and IGF-I levels were found in pubertal subjects alone (p less than 0.05). The urinary GH levels was significantly increased in prepubertal and pubertal subjects (p less than 0.001 and 0.05, respectively). A significantly inverse correlation between urinary GH excretion and creatinine clearance was found (r = -0.55; p less than 0.05). Increased plasma GH, IGF-I and urinary GH levels seem to suggest a complex alteration of GH and somatomedin metabolism in central and peripheral (receptor) cells. PMID- 2253257 TI - Surgical treatment of ectopic ureteroceles and the role of heminephrectomy with subtotal ureterectomy. AB - We evaluated 16 patients, 2 weeks to 8 years of age (median: 18 months), operated on for ectopic ureterocele. Five patients, in whom the upper kidney, drained by the ureter with the ureterocele, was viable, were submitted to excision of the ureterocele with reimplantation of the double ureter (n = 4) or high ureteroureterostomy (n = 1). A 2-week-old baby with a non-functioning kidney was treated by nephroureterectomy. The remaining 10 children with a non-functioning upper part of a duplex kidney were submitted to heminephrectomy with subtotal ureterectomy. In this group of patients no problems arose from the retained ureteral stump or the decompressed ureterocele, and vesicoureteral reflux accompanying the ureterocele resolved postoperatively in 6 of 10 ureters. PMID- 2253256 TI - Promoters and inhibitors of calcium urolithiasis in children. AB - We have evaluated the urinary excretion of promoting (calcium, phosphorus, uric acid, oxalate) and inhibiting (citrate, magnesium, glycosaminoglycans) factors of crystallization in subjects with idiopathic hypercalciuria and calcium urolithiasis and in a control group. The examined children had a free diet and were drug free for the last 2 weeks. They were not affected by malabsorption, D RTA, urinary tract infection, or urinary tract malformation (factors interfering with urinary excretion of citrate and oxalate). In the patients with calcium urolithiasis, the daily urinary excretion of oxalate was significantly higher (p less than 0.01), and the urinary excretion of citrate was significantly lower (p less than 0.001) than in the subjects with idiopathic hypercalciuria and in the control group. Among the subjects with idiopathic hypercalciuria, those aged 4-9 years had a significantly reduced, though in the normal range, urinary excretion of citrate as compared with those aged 10-15 years (362 +/- 189 and 503 +/- 198 mg/g creatinine/24 h, respectively; p less than 0.01). Our data show that hypocitruria may play an important role in the pathogenesis of urolithiasis in children with idiopathic hypercalciuria. In these cases, the urinary citrate excretion was not inversely related to age, as has been suggested by other authors. PMID- 2253258 TI - Retrospective diagnosis of Jeune's syndrome in two patients with chronic renal failure. AB - Two patients are reported who presented at the age of 12 1/2 years with advanced chronic renal failure. Clinical findings and renal histology were consistent with nephronophthisis. The retrospective diagnosis of Jeune's syndrome was possible in both. Cone-shaped phalangeal epiphyses of hands and feet and metaphyseal chondrodysplasia of femoral heads and necks were the prominent findings on skeletal survey. One patient had a small bell-shaped thorax; in the other this aspect was present on reevaluation of neonatal X-rays. Our patients support the view that nephronophthisis is the principal cause of renal failure in Jeune's syndrome and that a wider awareness of this association could lead to detection of more so far unrecognized patients. PMID- 2253259 TI - Congenital nephrotic syndrome associated with Lowe's syndrome. AB - Two cases of the oculo-cerebro-renal syndrome of Lowe are reported, in which the course of the disease was very fast and unusual. Within the first hours after birth the patients developed nephrotic syndrome and died at the age of 45 and 4 days, respectively. Renal tissue obtained by biopsy and at autopsy disclosed pronounced glomerular changes. PMID- 2253260 TI - Acute hypertensive encephalopathy in minimal change nephrotic syndrome. AB - A 3-year-old child with minimal change nephrotic syndrome (MCNS) developed an acute hypertensive encephalopathy characterized by coma, focal seizures, right hemiparesis, global aphasia and cortical blindness. Episodic hypertension and seizures persisted for 24 h despite intervention with antihypertensive and anticonvulsant therapy. Clinical suspicion of cortical blindness was confirmed by visual-evoked potential studies. CT scans performed 14 and 21 days after the acute episode demonstrated symmetric occipital white matter lucencies compatible with ischemia and/or associated edema. Hypertensive encephalopathy with cortical blindness and symmetric white matter hypodense lesions visualized on CT scan have recently also been described in eclampsia of pregnancy. This report documents an unusual acute hypertensive encephalopathy in childhood MCNS, unassociated with membranoproliferative glomerulonephritis, or progressive focal glomerulosclerosis. PMID- 2253261 TI - Opposite alterations in cerebrospinal fluid uridine after severe cerebral ischemia or intrathecal blood injection. AB - 1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells. PMID- 2253263 TI - Potassium channel blockade differentially affects the relative refractory period of frog afferent terminals and axons. AB - 1. The effects of potassium channel blockade on afferent axons and terminal regions in frog dorsal roots and spinal cords, respectively, were investigated in vitro. 2. A condition-test (C-T) protocol was used to assess the population relative refractory period. Characteristics of main axons were evaluated by stimulation at the proximal end of transected dorsal roots (DR). Characteristics of terminal regions were tested by stimulation at the base of the dorsal horn (DH). 3. DH recovery of excitability was delayed by low concentrations of 4 aminopyridine (4-AP) and tetraethylammonium (TEA) alone or combined. The same treatments did not affect recovery to DR stimulation. 4. DH recovery of excitability was not delayed by solutions suppressing terminal calcium influx. 5. We conclude that sensitivity of the relative refractory period to potassium channel blocking agents differs between main axons and axon terminal regions. This may indicate differences between axon terminals and main axons in the mechanism of action potential repolarization. 6. We hypothesize that rapid action potential repolarization by pharmacologically sensitive potassium channels in presynaptic terminal regions keeps terminal action potentials short. Terminal action potential brevity would limit calcium influx, thus preventing terminal calcium overload but contributing to transmission failures at spinal synapses. PMID- 2253264 TI - Regulation of nicotinic acetylcholine receptor function by adenine nucleotides. AB - 1. Nicotinic acetylcholine receptors (nAChR)4 from BC3H1 cells (which express a skeletal muscle-type receptor) and from Torpedo californica electric organ were expressed in Xenopus laevis oocytes and studied with a voltage-clamp technique. 2. We found that bath application of ATP in the micromolar to millimolar range increased the ACh-elicited current in both muscle and electrocyte receptors. The effect of ATP increased with successive applications. This "use-dependent" increase in potentiation was Ca2+ dependent, while the potentiation itself was not. 3. Four other nucleotides were tested on muscle nAChR: ADP, AMP, adenosine, and GTP. Of these, only ADP was a potentiator, but its effect was not use dependent. Neither ATP nor ADP affected the resting potential of the oocyte membrane. 4. ADP potentiated the response to suberyldicholine and nicotine, as well as ACh. 5. Finally, ADP reversed the phencyclidine-induced block of ACh currents in oocytes expressing muscle nAChR. PMID- 2253265 TI - [Analysis of 259 patients with myelodysplastic syndromes. The Czechoslovak MDS Cooperative Group]. AB - The authors analyze data of 259 patients assembled in seven haematological departments by the Czechoslovak cooperative MDS group and compare them with world wide groups. The mean age of 60 years of our patients is by 5-10 years lower than of groups reported abroad. In our group and in the majority of groups abroad refractory anaemia predominates over "preleukaemic" types of MDS. CMML is obviously a heterogeneous group from the diagnostic aspect. With the exception of CMML there is marked agreement as regards survival of different types of MDS starting with the longest survival of RAS, via RA, RAEB and finally the lowest survival of patients with RAEB-T. The diagnostic classification is thus to a certain extent also the prognosis of the patient with MDS. Transformation into AL (in 22% in our group) belongs to groups with a lower incidence of AL. Nevertheless more than 50% of the patients do not die from AL but from the sequelae of cytopenia. The incidence of secondary MDS (in the authors' group 13% patients, most frequently after mutagens) is mentioned in groups reported abroad only in one quarter of the papers. The incidence of chromosomal aberrations in our group is one of the highest in the world and along with the low average age of our patients is an alarming finding. PMID- 2253262 TI - Receptor-mediated presynaptic facilitation of quantal release of acetylcholine induced by pralidoxime in Aplysia. AB - 1. Possible interactions of contrathion (pralidoxime sulfomethylate), a reactivator of phosphorylated acetylcholinesterase (AChE), with the regulation of cholinergic transmission were investigated on an identified synapse in the buccal ganglion of Aplysia californica. 2. Transmitter release was evoked either by a presynaptic action potential or, under voltage clamp, by a long depolarization of the presynaptic cell. At concentrations higher than 10(-5) M, bath-applied contrathion decreased the amplitude of miniature postsynaptic currents and increased their decay time. At the same time, the quantal release of ACh was transiently facilitated. The facilitatory effect of contrathion was prevented by tubocurarine but not by atropine. Because in this preparation, these drugs block, respectively, the presynaptic nicotinic-like and muscarinic-like receptors involved in positive and negative feedback of ACh release, we proposed that contrathion activates presynaptic nicotinic-like receptors. 3. Differential desensitization of the presynaptic receptors is proposed to explain the transience of the facilitatory action of contrathion on ACh release. 4. The complexity of the synaptic action of contrathion raises the possibility that its therapeutic effects in AChE poisonings are not limited to AChE reactivation. PMID- 2253266 TI - [The effect of extreme endurance loading on the chronometry of cardiac systole]. AB - 1. Extreme long-term endurance loads of great intensity lead during the recovery period to significant changes of the preejection period and Weissler's index. The cause of this change is most probably the reversibly impaired contractility of the heart muscle after fatigue of the left ventricle as a result of a certain degree of overburdening. 2. Systolic time intervals are suitable means for the dynamic follow-up of the performance of the left ventricle in subjects after sports performances. PMID- 2253267 TI - [Best's calipers modified for examinations of obese patients]. AB - Assessment of the skinfold thickness in obese patients by means of a caliper makes it possible to determine the percentage of total body fat and provides information on the distribution of subcutaneous body fat and thus to characterize the type of obesity. In more severe obesity it is not possible to differentiate reliably by means of classical calipers larger skinfolds, in particular the subscapular and abdominal skinfold which thus makes these anthropometric examinations useless. A newly developed modification of the Best caliper makes it possible to measure reliably the majority of skinfolds in obese subjects as the arm of the caliper can be shifted to a range as high as 90 mm. Best's caliper provides, in contrary to others, the possibility to set a constant pressure when measuring the skinfold. In the discussion the authors draw attention to some methodological problems and the clinical importance of examining obese subjects by means of a caliper. PMID- 2253268 TI - [A simple method for estimating the level of physical fitness]. AB - Physical activity is becoming an integral part of everyday life. In order to modify and control this activity we need simple and readily available criteria for the control of physical fitness. One of the possible approaches how to resolve this problem is to use motor tests. The most frequently used method for evaluation of physical fitness proposed by Cooper, based on measurement in the American population may involve, when used under our conditions, inaccuracy of estimates of physical fitness and be associated with some difficulties regarding the 12-minute period of the test. The author submits therefore tables for the estimation of physical fitness elaborated with regard to our population standards and general relations between the velocity of movement and energy required for this activity expressed indirectly by oxygen consumption. The basic element of evaluation is the velocity of movement of a 2000 to 3000 m track. The tables were prepared for men and women aged 14-65 years and make it possible to estimate below-average, average and above-average levels of physical fitness. The error of assessment of VO2 max and thus also of the estimate of physical fitness level varies round 15%. PMID- 2253269 TI - [Arteriovenous fistula complicating central venous catheterization]. AB - Iatrogenic fistulae are sporadic but potentially serious complications of catheterization of central veins. The authors present the case-history of a 57 year-old patient with chronic renal failure where after 19 months following temporary insertion of a central venous catheter into the subclavian vein on the right from and infraclavicular approach a continual murmur was recorded in the right subclavicular area, along with increasing manifestations of left-sided cardiac insufficiency. Using digital subtraction angiography, the authors diagnosed an arteriovenous fistula between the internal thoracic artery and the right brachiocephalic vein. The described case draws attention to a rare complication of catheterization of the central veins and its possible haemodynamic sequelae. PMID- 2253270 TI - Functional analysis of the yeast genome: use of two-dimensional gel electrophoresis to detect genes in randomly cloned DNA sequences. AB - Genes are overexpressed when present in yeast cells on multicopy plasmids. Taking advantage of the protein amplification which results from this overexpression, a method has been developed for large scale detection of yeast genes on randomly cloned DNA sequences. It is based on the analysis, by two-dimensional gel electrophoresis, of the proteins from yeast cells transformed with a yeast genomic DNA library constructed in a multicopy vector. We demonstrate here the applicability of this method for exploring the yeast genome. In addition, we report results which suggest that this method may also be useful for detecting regulatory genes. PMID- 2253271 TI - Cloning and sequencing of a human cDNA coding for a multifunctional polypeptide of the purine pathway by complementation of the ade2-101 mutant in Saccharomyces cerevisiae. AB - A HeLa cell cDNA library on a yeast expression vector was used to complement auxotrophic markers of Saccharomyces cerevisiae. Clones complementing the ade2 101 mutation harbor a 1.5 kb poly(A)+ tailed insert with a 425 amino acid open reading frame hybridizing with two human mRNAs of 1.5 kb and 3.1 kb. Its 5' half is homologous to Bacillus subtilis SAICAR synthetase (E.C.6.3.2.6.) and its 3' terminal half corresponds to the catalytic subunit of Escherichia coli and B. subtilis AIR carboxylase (E.C.4.1.1.21). In agreement with these homologies, pADE2H1 clones complement both ade1 and ade2 mutants of S. cerevisiae, as was also recently reported for a 3.1 kb cDNA isolated from human hepatocytes. PMID- 2253272 TI - Functional analysis of the sporulation-specific SPR6 gene of Saccharomyces cerevisiae. AB - The SPR6 gene of Saccharomyces cerevisiae encodes a moderately abundant RNA that is present at high levels only during sporulation. The gene contains a long open reading frame that could encode a hydrophilic protein approximately 21 kDa in size. This protein is probably produced by the yeast, because the lacZ gene of Escherichia coli is expressed during sporulation when fused to SPR6 in the expected reading frame. SPR6 is inessential for sporulation; mutants that lack SPR6 activity sporulate normally and produce viable ascospores. Nonetheless, the SPR6 gene encodes a function that is relevant to sporulating cells; the wild-type allele can enhance sporulation in strains that are defective for several SPR functions. SPR6 is located on chromosome V, 14.4 centimorgans centromere-distal to MET6. PMID- 2253274 TI - Analysis of large deletions in the Mauriceville and Varkud mitochondrial plasmids of Neurospora. AB - The Mauriceville and Varkud mitochondrial plasmids are closely related, closed circular DNAs (3.6 and 3.7 kb, respectively) that have characteristics of mtDNA introns and retroid elements. Both plasmids contain a 710 amino acid open reading frame (ORF) that encodes an 81 kDa protein having reverse transcriptase activity. Here, we analyzed two mutant plasmids, V5-36 and M3-24, that have undergone relatively large deletions (approximately 0.35 and 0.5 kb, respectively). Both deletions occur downstream of the long ORF in a non-coding region of the plasmids that contains a direct repeat of 160 bp and a cluster of five PstI-palindromes, a repetitive sequence element in Neurospora mtDNA. In V5-36, the deletion end points are at the bases of two hairpin structures that are centered around PstI palindromes and flank the deleted region. In M3-24, the deletion junction contains an extra T-residue that is not encoded in the plasmid. In both plasmids, the deletion end points do not correspond to homologous or directly repeated sequences of more than one nucleotide, whose pairing could account for the deletion junction. The characteristics of the deletion end points can be accounted for either by illegitimate recombination, possibly following double strand breaks at cruciform structures, or by interruption of reverse transcription followed by reinitiation downstream. The finding that the deletions encompass the 160 bp direct repeat and all five PstI-palindromes indicates that neither are required for propagation of the plasmids and supports the hypothesis that PstI-palindromes are selfish DNA elements that inserted into a nonessential region of the plasmid. PMID- 2253273 TI - Structure and expression of a single actin gene in Volvox carteri. AB - Southern blot analysis of Volvox carteri DNA indicated the presence of a single actin gene; the nucleotide sequence of that gene is reported here. In comparison with plant animal and fungal actins, the derived primary structure of 377 amino acids is highly conserved yielding similarity values of 79% to 94% (including non identical conservative exchanges). In contrast, the intron structure of the gene is highly unusual: in addition to one intron in the 5' untranslated region (ten nucleotides upstream of the initiator ATG), it has eight introns in the coding region, only three of which are in locations where introns have previously been reported. Transcription starts 26 nucleotides downstream of the putative TATA box and 70 nucleotides downstream of a conspicuous CCAAT motif. A potential polyadenylation signal, TGTAA, is located 366 nucleotides downstream of the terminator TAA. Northern hybridization indicates that the actin gene is transcribed throughout the Volvox life cycle with only a slight depression during the release of juveniles from mother spheroids. This pattern of gene expression suggests that actin may assume various functional roles in the differentiation and growth of Volvox. PMID- 2253276 TI - Electrophoretic karyotyping without the need for generating protoplasts. AB - Chromosome samples for pulsed-field electrophoresis have been prepared without first generating protoplasts. The technique involves treatment of intact, agarose solidified cell material with protease in the presence of EDTA and SDS. Saccharomyces cerevisiae, Ustilago hordei, Tilletia caries, and T. controversa karyotypes are clearly resolved with this technique. Colonies of U. hordei and S. cerevisiae removed from the surface of agar-solidified media and prepared for PFGE by this abbreviated method also yield well resolved karyotypes. PMID- 2253277 TI - [Law, medicine and health care]. PMID- 2253275 TI - The chloroplast psbK operon from mustard (Sinapis alba L.): multiple transcripts during seedling development and evidence for divergent overlapping transcription. AB - The mustard chloroplasts genes psbK and psbI are co-transcribed, giving rise to precursor transcripts of several size classes, which are processed to the monocistronic mature RNAs. The psbK and psbI coding regions are flanked by the two tRNA genes trnS-GCU and trnQ-UUG on the opposite DNA strand. Transcript mapping indicates that the (primary) psbK-psbI transcript overlaps the complete trnS-GCU and trnQ-UUG transcripts. The transcription start site of the psbK operon appears to overlap that of the rps16 gene. During seedling development, the psbK and psbI precursors and mature transcripts all become detectable between 30 and 48 h after sowing and then remain at constant levels without much difference either in light or in darkness. PMID- 2253278 TI - [The rights of citizens for health care consistent with findings in modern medicine]. PMID- 2253279 TI - [Administrative legal guarantees of the rights of citizens to preventive health care in Czechoslovakia]. PMID- 2253280 TI - [Decision-making by the physician in situations of life and death]. PMID- 2253281 TI - [The role of anesthesiology and resuscitation in the care of patients in terminal states]. PMID- 2253282 TI - [Contraception from the aspect of present legal reforms]. PMID- 2253283 TI - [Saving life versus respect for the wishes of the patient (views of physicians on ethics and the law]. PMID- 2253284 TI - [Informed consent by patients in the laws of socialist countries]. PMID- 2253285 TI - [Codification of health care in socialist countries]. PMID- 2253286 TI - [The Spanish laws in 1988 regarding the handling of human genetic material]. PMID- 2253287 TI - [Attitudes of medical students toward smoking]. AB - The investigation made by questionnaire was focused not only on the number of smokers but also on attitudes and knowledge of third year students of the Faculty of General Medicine, Charles University, towards smoking. At the same time a partial view of the lifestyle and subjective evaluation of the health status was obtained. The data were compared also with the results of other surveys published in the literature. PMID- 2253288 TI - Surveying anaesthesia. PMID- 2253289 TI - Catecholamines and neuraxial anaesthesia. PMID- 2253290 TI - Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia. AB - This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect. PMID- 2253291 TI - Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery. AB - A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs. PMID- 2253292 TI - Oral transmucosal fentanyl citrate for premedication in paediatric outpatients. AB - Two doses (10-15 micrograms.kg-1, Group I, and 15-20 micrograms.kg-1, Group II) of oral transmucosal fentanyl citrate (OTFC) plus a placebo (Group III) were evaluated for premedication in 105 healthy children, aged 2 to 13 yr, undergoing short (less than 1 hr) operations in the hospital short-stay unit. The study was randomized and double-blinded and 91 of the 105 children also received droperidol, 25 micrograms.kg-1 IV, after induction of anaesthesia with halothane and N2O in oxygen. Both doses of OTFC produced significantly greater sedation (first present at 20 min) and anxiolysis (first present in Group I at 40 min) than the placebo. Recovery times were similar in the three groups and analgesic requirements in the recovery room were significantly lower in Group I than Group III. Both OTFC groups took longer to tolerate oral fluids in the postoperative discharge unit than the placebo group and this caused patients in Group I to have a delayed discharge from the hospital compared to Group III. Preoperative pruritus occurred significantly more frequently in Groups I and II (58 and 76 per cent, respectively) than Group III (23 per cent). Although the incidences of nausea and vomiting tended to be slightly higher in the OTFC groups in the preoperative holding and postoperative discharge units, the differences among the groups were not statistically significant. Likewise droperidol did not reduce the incidence of postoperative nausea or vomiting. The data indicate that OTFC may be a safe and effective premedicant in paediatric patients having short operations but delays discharge from the hospital (by 30-50 min) by delaying the time patients tolerate fluids early after operation. PMID- 2253293 TI - Halothane anaesthesia does not modify the cardiovascular response to phenylephrine in man. AB - Conflicting results exist regarding the ability of halothane to alter the vascular response to alpha 1 adrenergic agonists in animals. Because data from humans are lacking, we studied the haemodynamic response to phenylephrine (PHE) in eight patients about to undergo coronary artery bypass surgery before and during halothane anaesthesia. After obtaining baseline measurements in patients while awake, the responses to PHE infusion at 30, 40, and 50 micrograms.min-1 were determined. New baseline measurements were made following stabilisation during anaesthesia with halothane, one per cent inspired in oxygen, prior to surgical incision. Then the responses to identical PHE doses were measured again. Halothane did not influence the cardiovascular response to PHE: there was no dose response shift for any cardiovascular variable. No arrhythmias or signs of ischaemia were observed. We conclude that one per cent halothane anaesthesia does not attenuate PHE-induced vasoconstriction in man. PMID- 2253294 TI - Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block. AB - The purpose of this study was to determine the pharmacokinetic properties of the local anaesthetic ropivacaine used with or without epinephrine for brachial plexus block. Seventeen ASA physical status I or II adult patients undergoing elective orthopaedic surgery received a single injection of 33 ml ropivacaine for subclavian perivascular block and 5 ml to block the intercostobrachial nerve in the axilla. One group (n = 8) received 0.5 per cent ropivacaine without epinephrine (190 mg) and the other (n = 9) received 0.5 per cent ropivacaine with epinephrine 1:200,000 (190 mg). Plasma ropivacaine concentrations were measured from peripheral venous blood samples taken for 12 hr after drug administration. Ropivacaine base was determined in plasma using gas chromatography and a nitrogen sensitive detector. The mean peak plasma concentration (Cmax) was 1.6 +/- 0.6 mg.L-1 and 1.3 +/- 0.4 mg.L-1 after administration of ropivacaine with and without epinephrine. The median time to peak plasma concentration (tmax) was 0.75 hr and 0.88 hr and the mean area under the plasma concentration curve AUC0-12h was 7.7 +/- 3.6 and 7.0 +/- 3.4 mg.l hr-1. The differences were not statistically significant. The terminal phase of the individual plasma concentration-time curves showed a varying and sometimes slow decline possibly indicating a sustained systemic uptake of ropivacaine from the brachial plexus. No central nervous system or cardiovascular symptoms attributed to systemic plasma concentrations of the drug were observed, with the dose (1.90-3.28 mg.kg-1) of ropivacaine used. It is concluded that the addition of epinephrine does not alter the pharmacokinetic properties of ropivacaine when used for subclavian perivascular brachial plexus block. PMID- 2253295 TI - The upgrading and replacement of anaesthetic equipment: a provincial approach. AB - A formal on-site survey of all anaesthetizing locations in the Province of Manitoba was initiated in the Spring of 1988. Serious deficiencies of anaesthetic equipment previously noted on random survey were confirmed. Recognizing a need for improved standards for delivery of anaesthetic services through safe, functional anaesthetic equipment, the province undertook to fund the upgrading of all anaesthetic gas delivery systems under its jurisdiction. Sixty-six hospitals were surveyed for a total of 203 anaesthetic machines (111 urban, 92 rural). One hundred and sixty-seven machines had been used at least once in the previous year. After careful assessment 92 machines were replaced, 66 machines were upgraded and 45 machines were deleted from further service. Although the maintenance and upgrading of medical equipment is the individual health care facility's responsibility, substantial benefit was recognized by a provincial approach. The authors recommend a similar approach for other Canadian provinces. PMID- 2253296 TI - Post-cannulation radial artery aneurysm--a rare complication. AB - The following case report describes an expanding aneurysmal dilatation of the radial artery which developed 17 days following cannulation. Possible causes of this complication are: abnormal state of the vessel wall, multiple attempts at cannulation, and haematoma or infection at cannulation site. Other major and minor sequelae following arterial cannulation are reviewed. PMID- 2253297 TI - Amyloidosis associated bleeding diatheses in the surgical patient. AB - The coagulopathies associated with amyloidosis have not been widely appreciated. We encountered a patient with amyloidosis and mildly abnormal coagulation studies who presented for an emergency laparotomy for acute bowel obstruction. Upon gentle manipulation of the bowel, an unexpected bleeding diathesis was manifested by the formation of several large haematomas resulting in a large amount of blood loss (approximately 800 ml). Numerous defects of platelet function and coagulation have been associated with amyloidosis, including abnormal platelet aggregation, increased vascular fragility, factor IX and X deficiencies, decreased levels of alpha-2-plasmin inhibitor, and increased levels of plasminogen. Intraoperative therapy for our patient included the rapid administration of four units of fresh frozen plasma and ten units of platelet concentrate. A review of the pathology and therapeutic modalities for this potentially life-threatening complication is presented. PMID- 2253298 TI - Crico-tracheal disruption and common carotid artery occlusion: a case of blunt trauma. AB - A case of blunt trauma to the neck is presented. While driving an all terrain vehicle (ATV), a 20-yr-old male was struck across the anterior neck by a cord suspended between two poles. Initial findings were suggestive of an isolated laryngeal injury; 48 hours later, however, a dense left hemiplegia became manifest. A CT scan demonstrated a large right frontoparietal cerebral infarct, and an angiogram confirmed occlusion of the right common carotid artery. Intractable cerebral oedema developed, and the patient died five days after the initial insult. Such injuries should alert the clinician to the possibility of major vascular injury, and if suspected, angiography is warranted. PMID- 2253300 TI - Nicardipine reduces the cardio-respiratory toxicity of intravenously administered bupivacaine in rats. AB - The purpose of our study was to examine the effect of intravenous (IV) nicardipine pretreatment (30 micrograms.kg-1), given three minutes before an IV bolus of bupivacaine to determine its effect on the incidence of fatal bupivacaine cardio-respiratory toxicity in adult male Sprague Dawley rats anaesthetized with intraperitoneal pentobarbital. Fifty rats were divided into four groups. Groups I and II (n = 10 each) received 3.5 mg.kg-1 0.5 per cent bupivacaine and Groups III and IV (n = 15 each) received 5.0 mg.kg-1, 0.5 per cent bupivacaine. Groups I and III received pretreatment with normal saline before bupivacaine, whereas Groups II and IV were given pretreatment with nicardipine, 30 mg.kg-1. There was no difference in the incidence of survival between the nicardipine pretreatment group and the saline placebo pretreatment group given 3.5 mg.kg-1, 0.5 per cent bupivacaine (no fatalities in either group). However, there was significant protection by nicardipine pretreatment in the group given 5 mg.kg-1, 0.5 per cent bupivacaine (13 of 15 survived, compared with only 4 of 15 in the saline pretreatment group, P less than 0.001). In conclusion, our data demonstrate that in rats given 0.5 per cent bupivacaine, 5 mg.kg-1, nicardipine pretreatment protected against fatal cardio-respiratory toxicity. PMID- 2253299 TI - In vitro effects of fluoride and bromide on pseudocholinesterase and acetylcholinesterase activities. AB - The in vitro effects of two metabolites of inhalational anaesthetics, fluoride and bromide, on pseudocholinesterase (PCHE) and acetylcholinesterase (ACHE) activities in the blood samples of seven healthy patients were studied. The PCHE and ACHE activities were determined by kinetic spectrophotometric methods. Fluoride at the levels achieved with clinical concentrations of enflurane and sevoflurane (25-75 microM.L-1) inhibited PCHE activity by 28-65 per cent (P less than 0.01) and ACHE activity by less than five per cent (P greater than 0.05). Bromide at the levels achieved with clinical concentrations of inhalational anaesthetics had no significant effect on either PCHE or ACHE activity. We recommend caution when succinylcholine and/or ester type local anaesthetics are used in the immediate postoperative period following enflurane or sevoflurane anaesthesia. We also recommend that blood drawing for PCHE activity be delayed at least until 24 hr following enflurane or sevoflurane anaesthesia. PMID- 2253302 TI - History of Canadian anaesthesia. William Bayard 1814-1907. PMID- 2253301 TI - Re-evaluation of the Farman entrainer in a low-pressure system for field anaesthesia. AB - The aim of this project was to develop a portable anaesthesia system that was compatible with modern anaesthesia practice under field conditions, when compressed gas supplies are limited. We assembled and evaluated a low-pressure plenum system, based upon the Farman entrainer, which was adaptable to spontaneous, assisted or intermittent positive pressure ventilation (IPPV). The entrainer was tested using a low flow of compressed gas, O2 at 1-3 L.min-1. We measured the fresh gas flow (FGF) and O2 concentrations (F1O2) delivered at various source gas flow rates (O2 flow), and with various breathing circuits. Entrainment ratio, FGF, and F1O2 were highly dependent upon resistance to flow in the different breathing circuits. With a wide bore T-piece the air/O2 entrainment ratio was 6:1, and the F1O2 was 0.3. When circuit resistance was higher, e.g., with the Bain circuit, air entrainment and FGF were reduced, but F1O2 was higher. Because it offered the lowest resistance, the T-piece circuit was selected for a clinical trial. PMID- 2253303 TI - Regional anaesthesia for 12,000 cataract extraction and intraocular lens implantation procedures. PMID- 2253304 TI - Anaphylactoid reactions following propofol-atracurium sequence. PMID- 2253305 TI - Low-dose intrathecal-meperidine for lower limb orthopaedic surgery. PMID- 2253306 TI - Intra- and postoperative management of craniosynostosis. PMID- 2253307 TI - Triple lumen catheter: a potential hazard. PMID- 2253308 TI - "Dental trauma" to oral airways. PMID- 2253309 TI - Canadian Anaesthetists' Society medal. Emerson A. Moffitt. PMID- 2253310 TI - Human melanoma: development and progression. AB - Clinical and histopathological evidence suggests that melanoma develops in a sequence of steps, progressing from benign proliferative lesions, to primary melanomas that do not show evidence for metastasis, to invasive primary lesions, and to metastases. This review focuses on the experimental studies examining the phenotypic characteristics of cultured primary melanoma cells as they relate to cells from non-malignant nevi and metastases. Genetic, biologic, and immunologic criteria have been established to distinguish melanocytes from different steps of tumor development. These include non-random chromosomal abnormalities, expression of melanocyte- and melanoma-specific antigens, requirements for exogenous growth factors, production of endogenous growth factors, and expression of receptors for growth factors. The transformation of melanocytes and nevus cells with viral oncogenes has facilitated studies on the malignant phenotype. Variants have been developed through successive selections from primary melanoma cell populations that have one or several characteristics of metastatic cells. The study of melanocytes isolated from various stages of tumor development and the generation of cell variants with specific properties should enable a long-term search for the molecular mechanisms of melanoma development and progression. PMID- 2253312 TI - Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment. AB - Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma. Canine osteosarcoma is a malignant aggressive bone tumor with a 90% metastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers. Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies. Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches. Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers. Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers. This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology. PMID- 2253311 TI - Cell-matrix interactions during tumor invasion. AB - This manuscript reviews the molecular aspects of tumor cell invasion of extracellular matrix. The changes in cell:substrate and cell:cell receptors that characterize motile cells are discussed for their importance not only in mediating invasive cell behavior, but also as diagnostic markers for invasive potential. Autocrine motility and scatter factors probably have key roles in initiating migratory behavior, while specific and non-specific extracellular matrix alterations can facilitate cell locomotion. The manuscript reviews reported changes, such as induction of cell motility, matrix degrading enzymes, and invasive/metastatic potential, which can follow transfection with ras oncogenes, and details the key roles of metalloproteinases, heparanase, and plasminogen activator in matrix degradation. Enzymatic inhibitors of initial steps in extracellular matrix degradation, such as rTIMP, and synthetic blockers of adhesive steps in tumor cell invasion represent types of reagent with potential as anti-metastatic agents. Their potential usefulness may be increased if they can be incorporated into a novel, long-term, non-traditional delivery system. PMID- 2253313 TI - Tumor progression: potential role of unstable genomic changes. AB - It is generally accepted that the genome of tumor cells is less stable than that of most normal cells, and it has been hypothesized that this genomic instability is probably involved in the process of tumor progression. However, the rate of occurrence of classical spontaneous mutations in tumor cells is too low to account for the rapid changes that can occur during tumor progression. Thus it is likely that other types of changes, such as gene amplification, must be involved in tumor progression. Gene amplification has been extensively studied in relation to the development of drug resistance. Low levels of amplification can occur spontaneously in tumor cell populations, but the amplified genes are lost rapidly unless prolonged selective pressure is applied. This paper argues that unstable increases in the expression of genes, probably as a result of low levels of amplification, may be all that is required for some of the stages in the process of tumor progression. This may be particularly true for the steps involved in metastasis formation. Recent studies have suggested that microenvironmental conditions known to occur in tumors (hypoxia, nutrient deprivation) may induce gene amplification in cells. This suggests the possibility that such conditions could promote tumor progression. PMID- 2253315 TI - Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat. AB - Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats. PMID- 2253316 TI - Effect of histamine receptor antagonists on mortality in compound 48/80-induced shock. AB - The roles of histamine and H1 and H2 receptors in shock are uncertain. We have found that treatment of aged rats with compound 48/80 (a mast cell degranulator) produced lethal (LD99) shock which was completely prevented by lodoxamide (LOD), a mast cell degranulation inhibitor. This study evaluated the effect of H1 and H2 receptors and age on mortality of 48/80-induced shock in rats. To assess survival, 65 young male (125 g), 65 mature male (250 g) and 30 aged male (500 g) SD rats were placed in groups and treated intraperitoneally with saline; 48/80; LOD + 48/80; the H1 blocker diphenhydramine (DPH) + 48/80; the H2 blocker cimetidine (CIM) + 48/80; or DPH and CIM + 48/80. Rats were observed for 30 min or until death. All 125 g rats survived. Of the 250 g rats, 50% of 48/80-treated and 100% of CIM + 48/80-treated rats died; all others survived. All 500 g 48/80- and CIM + 48/80-treated rats died; all other 500 g rats survived. For all ages, survival differences between saline-, 48/80-, and CIM + 48/80-treated rats were highly significant (P less than or equal to 0.0001). In addition, both 48/80 and CIM + 48/80 greatly reduced mean survival time in the 250 g and 500 g groups (P less than or equal to 0.0001) compared to all other treatments. Both LOD and DPH were protective against 48/80, and DPH was also protective against CIM + 48/80, for both absolute survival and mean survival time (P less than or equal to 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253314 TI - Orthotopic implantation is essential for the selection, growth and metastasis of human renal cell cancer in nude mice [corrected]. AB - Human neoplasms are heterogeneous for a variety of biological properties that include invasion and metastasis. The presence of a small subpopulation of cells with a highly metastatic phenotype has important clinical implications for diagnosis and therapy of cancer. For this reason, it is important to develop an animal model for the selection and isolation of metastatic variants from human neoplasms and for testing the metastatic potential of human tumor cells. We have implanted human renal cell carcinoma (HRCC) cells (obtained from a surgical specimen) into different organs of nude mice and then recovered the tumors and established each in culture. The 5 established lines differed in their biological metastatic properties and had a unique karyotype, indicating that growth at different organs selects for different subpopulations of HRCC. Moreover, the HRCC did not metastasize unless they were implanted orthotopically. These findings indicate that the appropriate nude mouse model for studying the biology and therapy of HRCC must be based on the orthotopic implantation of tumor cells. PMID- 2253317 TI - Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. AB - Previous studies of hypothermia and blood coagulation have focused on alterations in the levels of blood clotting elements using coagulation tests performed under normothermic conditions. However, because of the enzymatic nature of activated clotting factors, hypothermia should also be expected to affect clotting factor activities. Multiple determinations of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on commercially available normal human plasma at assay temperatures similar to those encountered clinically (25-37 degrees C). Both the APTT and the PT were significantly prolonged at temperatures below 35 degrees C (P less than 0.05). Clotting time correlated significantly with assay temperature in a negative exponential fashion for all three tests (r = -0.97 for APTT, -0.93 for PT, -0.71 for TT, P less than 0.001 for all regressions). Clotting time prolongation appears proportional to the number of enzymatic steps involved. These data indicate that the coagulopathy observed during hypothermia is, in part, independent of clotting factor levels. PMID- 2253318 TI - Contribution of platelet activating factor to hemodynamic and sympathetic responses to bacterial endotoxin in conscious rats. AB - The effect of the platelet activating factor (PAF) antagonist WEB 2086 on blood pressure; heart rate; and plasma glucose, lactate, and catecholamine concentrations were examined following either PAF or endotoxin administration in conscious rats. PAF infusion (50 ng/kg/min for 60 min) resulted in a sustained hypotension, with tachycardia and elevated plasma norepinephrine (NE; 1.8-fold increase), epinephrine (E; 6.7-fold increase), and dopamine (DA; 1.0-fold increase) at 30 min after beginning infusion. Plasma NE, E, and DA became 4.1 (NE)-, 17.4 (E)-, and 3.3 (DA)-fold higher than control at 60 min after beginning infusion. Both the hemodynamic and plasma catecholamine alterations induced with PAF were completely blocked with WEB 2086 pretreatment. Bacterial endotoxin treatment (5 mg/kg, i.v. bolus) produced well-characterized responses of hypotension, tachycardia, hyperglycemia, hyperlactacidemia, and an elevation in plasma catecholamines. Whereas complete blockade of the hypotensive and tachycardic effect of endotoxin was achieved with WEB 2086 at 30 min following endotoxin, the increases in plasma catecholamines and lactate elicited by endotoxin were attenuated but remained significantly higher than control levels. Hyperglycemia following endotoxin was not altered by WEB 2086 treatment. In endotoxic rats pretreated with WEB 2086 there was significant hypotension, tachycardia, and hyperlactacidemia and an elevation in plasma catecholamines at both 60 and 120 min, but all were less severe compared to non-WEB 2086-treated endotoxic animals. The results demonstrate that WEB 2086 completely blocked early endotoxin-induced hypotension and tachycardia but not catecholamine elevation following endotoxin. This work suggests that sympathetic activation following endotoxin may be mediated by factors other than hypotension. PMID- 2253319 TI - Estrogen-independent and estrogen-induced progesterone receptors, and their regulation by progestins in the hypothalamus and pituitary of the chick embryo: an immunohistochemical study. AB - The effects of an anti-estrogen and of progestins on the progesterone receptor (PR) in the hypothalamus and pituitary of 10-day-old chick embryos were studied by immunohistochemistry with an antibody to the receptor. In a first experiment, to determine if endogenous estrogens are responsible for the early appearance of PR in the chick embryo, a continuous treatment with the anti-estrogen. Tamoxifen, was applied from day 0 of incubation. In the hypothalamus and pars distalis of the pituitary a Tamoxifen treatment (10 micrograms every other day from day 0) did not modify the distribution of PR-positive cells or the intensity of PR immunoreactivity (PR-IR), compared to oil-injected embryos. In contrast, the same treatment totally blocked the increase of PR-IR in embryos administered estradiol (10 micrograms on day 7). Thus, the estradiol-induced PR-IR is inhibited by Tamoxifen, whereas the natural appearance of PR is not. We conclude that, in the chick embryo, the basal expression of PR is estradiol independent. In a second experiment, the regulation of PR by its own ligands (progesterone and the synthetic progestin, R5020) was studied. Progesterone (150 micrograms), administered to embryos 16 or 48 h before sacrifice on day 10, induced a slight increase in PR-IR in hypothalamus and anterior pituitary, whereas R5020 had no effect. In embryos treated with estradiol on day 7, R5020 decreased the PR-IR to a level comparable to that of control embryos. Thus R5020, a non metabolizable progestin, down-regulates the estradiol-induced PR-IR, but has no effect on the estradiol-independent, naturally expressed PR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253320 TI - Ontogenesis of the secretory epithelium of the bovine subcommissural organ. A histofluorescence study using lectins and monoclonal antibodies. AB - A spatio-temporal analysis of the differentiation of a group of specialized (secretory) ependymal cells in the subcommissural organ (SCO) of the brain was undertaken in the bovine using a monoclonal antibody (C1B8A8) which is specific of the secretory process in this organ. In addition, lectins (concanavalin agglutinin (Con A), Lens culinaris agglutinin (LCA), wheat germ agglutinin (WGA), and Phaseolus vulgaris agglutinin (PHA] were used to analyse the maturation of the carbohydrate moieties of the secretory product (subcommissuralin). Monoclonal antibody NC-1 specific to a complex carbohydrate epitope including a terminal 3 sulfoglucuronyl residue similar to HNK-1 was also tested to compare the reactivity of the SCO with that of other brain structures. These cells express a specific antigen related to the known secretory activity of the SCO during early embryogenesis (2 months). This antigen is recognized by C1B8A8 antibody and by Con A suggesting that high mannose-type glycoproteins are synthesized at this stage. Later on (approximately 3.5 months), appearance of C1B8A8, WGA, LCA, L- and E-PHA-positive material in the apical lining of the ependymal cells, close to the ventricular cavity, suggests that maturation of the complex-type glycoproteins (Asn-linked) occurs at this stage. Presence of secretory material in the CSF and Reissner's fibre could be detected using the same probes at a stage of 4 months. As early as 2 months NC-1-positive material was detected in the ependyma of the mesencephalic roof, while no reaction occurred in the SCO epithelium. This suggests that the carbohydrate moieties of subcommissuralin is different from that of ependymins beta and gamma. Using specific monoclonal antibodies, molecular characterization of subcommissuralin and experimental analyses on its accurate role in brain development will further our tentative comparison with ependymins. The secretory ependymal cells in the SCO express a particular phenotype and could represent an increasing model to study cell differentiation in the brain. PMID- 2253321 TI - A position-dependent transgene reveals patterns of gene expression in the developing brain. AB - We have made a detailed analysis of the developing mouse brain using a transgene (HSVtk-lacZ), whose expression is dependent on its unique site of integration. The position-dependent transgene expression defines a novel pattern of gene expression in the developing mouse brain. The transgene is first transcribed on day 10 of gestation in a small cluster of cells in the developing hind brain. Extensive expression is subsequently seen in a number of developing brain structures (cortex, cerebellum, hippocampus), but postnatally this becomes restricted to cell types within distinct anatomical foci principally associated with the olfactory system. Expression in the olfactory system is maintained even into adulthood. Hence, the expression of this transgene is confined to cell types which are known from other studies to sustain developmental plasticity in embryos and in adults. It will be of interest to analyse the transgene pre-integration site and determine if endogenous genes at this locus are also expressed in these cells and if they have a role in maintaining their developmental potential. PMID- 2253322 TI - Four patterns of laminin-immunoreactive structure in developing rat brain. AB - Laminin has been known to promote neurite outgrowth in culture. We have recently demonstrated that laminin facilitates and guides fiber growth of grafted neurons in the brain. In this study, I report that 4 distinct patterns of laminin immunoreactivity--small and large punctiform laminin, sheath laminin, and somal laminin--were expressed in the brain, each having unique spatial and temporal distributions. They are extensively produced in the developing brain while nerve fibers and vessels are actively growing. Two patterns of laminin, small and large puncta, disappear when the brain matures; the other two, sheath laminin and somal laminin, reduce in intensity but persist through adult life. The small puncta, size less than 1 micron in diameter, frequently accumulated along acellular spaces where future fiber bundles will form, interneuronal spaces and surfaces of neurons where terminal fibers dwell, and around the microvessels where neomicrovessels form. The small puncta, which reportedly appear at the eight-cell stage, were observed in our study at stage E10. They increased in expression from E14 to 19 during the stage when many nerve fibers are navigating to their targets, and subsided in the early postnatal days (P6) when less fiber growth occurs. Large puncta, size about 2 microns in diameter, existed exclusively in the hippocampus. They appeared about E16, and ended P16. The sheath laminin is known to form wrappings on microvessels, the ependymal layer, the choroid plexus, and the surface of the brain. This pattern of laminin attaches to non-neuronal structures which associate with CNS fluid. It was detected at E10 (our youngest group), increased its distribution along with expansion of the associated structure, and persisted throughout the adult life. The somal laminin, associated mainly with the soma of neurons, was the latest appearing laminin pattern (not until E16). It also persisted through adult life in the brain. The somal laminin, which was highly associated with the appearance of neuronal groups in brain nuclei, appeared group by group along with neurons. In summary, laminin attaches with distinct groups of cells in the central nervous system with specific temporal association. This close temporal and spatial association may allow laminin to actively affect nerve growth during brain development. The detailed mapping of laminin distribution is in progress in our lab. PMID- 2253323 TI - Neuron-glia cell adhesion molecule (Ng-CAM) expression in the chick embryo spinal cord: observations on the earliest developing intersegmental interneurons. AB - The pattern of expression of the neuron-glia cell adhesion molecule (Ng-CAM) among the presumptive intersegmental interneurons in the early chick embryo spinal cord (stage 14-19) was examined using whole-mount and cryostat preparations double-stained with anti-Ng-CAM antibody and a neuron-specific anti beta-tubulin antibody. In brachial segments, primitive longitudinal cells (PL cells), located in the ventrolateral region of the spinal cord, express Ng-CAM both on their cell bodies and longitudinally growing axons, beginning at Hamburger-Hamilton stage 15 (embryonic day (E) 2.5). Shortly thereafter, at stage 16, circumferential cells (C-cells), composed of associational and commissural interneurons in the dorsolateral and lateral region of the spinal cord begin to express Ng-CAM both on their cell bodies and their axons which project ventrally along the lateral surface of the spinal cord. In the following stages. PL-cells express Ng-CAM strongly and begin to fasciculate to form a longitudinal fascicle in the ventrolateral marginal region of the spinal cord. C-Cells either extend their Ng-CAM-positive axons ventrally without fasciculation to join the Ng-CAM positive ipsilateral longitudinal fascicle at stage 17 (which has already been formed by PL-cell axons), or they cross the midline to join the Ng-CAM positive contralateral longitudinal fascicle after growing through the floor plate at stage 19. By stage 19, cell bodies and proximal segments of the C-cell axons exhibit decreased Ng-CAM expression, whereas the distal segment of these axons, including growth cones, strongly express Ng-CAM. Many contacts were observed between Ng-CAM-positive growth cones and axons in the ventral region of the spinal cord, both within the longitudinal fascicle and the floor plate region, suggesting the involvement of Ng-CAM in neurite-neurite interactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253324 TI - Microglia and cell death in the developing mouse cerebellum. AB - The appearance and distribution of microglia in the developing cerebellum has been examined with the aid of a peroxidase-conjugated lectin derived from Griffonia simplicifolia. This distribution has in turn been correlated with that of pyknotic figures in the same Nissl-counterstained sections, in order to gain an understanding of the role of microglial in the developing cerebellum. Round and ameboid microglia may be recognised in the fetal cerebellum as early as E11. Numbers of microglia increase steadily from that time, with initial concentrations in the region of the dorsal and ventricular surfaces. By P1, concentrations of both pyknotic figures and ameboid microglia begin to appear in the region of the future cerebellar medulla. Ameboid microglia are recognisable in the cerebellar medulla until P10, with particular concentrations where folia branch and in the rostral cerebellar peduncles. After this time only resting microglia are found in the cerebellum. Concentrations of microglia largely match the positions of pyknotic figures throughout development, except at P10 and P14, when cell death is found in the external granular layer without an accompanying concentration of microglia. Electron microscopic examination of the phagosomes of ameboid microglia at P5 and P6 indicates that these cells are mainly concerned with the phagocytosis of entire cells rather than axons. Cell death in the cerebellar medulla may serve to clear pathways for developing cortical afferents and efferents, or to increase the mechanical plasticity of the medulla during cortical folding. PMID- 2253325 TI - Local cerebral glucose utilization in normoxemic and hypoxemic newborn lambs. AB - To determine if hypoxemia altered local cerebral glucose utilization (LCGU) in newborn lambs, and where these alterations occurred, we measured LCGU using the 2 [14C]deoxyglucose [( 14C]DG) autoradiographic technique in lambs made hypoxemic by gradual reduction in inspired oxygen concentration. In 5 normoxemic control lambs, aged 3 days. LCGU of the cerebral cortex and white matter was higher than published values of LCGU in similar structures in near term normal fetuses and 2 4 times higher than reported values in normoxemic puppies. LCGU was highest in vestibular nuclei and auditory structures, followed by cerebellar nuclei, cerebral subcortical structures, and white matter. In 6 hypoxemic newborn lambs (paO2 14-18 torr) consistent increases in LCGU were noted only in the corona radiata compared to the values obtained in the normoxemic control lambs (36.5 +/- 8.1 vs. 23.9 +/- 1.7 mumol/100 per min, mean +/- S.D., P less than 0.02). This increase in LCGU in white matter was clearly noted in autoradiographs in which thin dark central regions within white matter often reached high into the gyri. In the hypoxic group. LCGU of the corona radiata superseded the value in many gray matter structures. In addition, patchy increases of [14C]DG utilization were present in the cerebral cortex of two hypoxemic lambs. Acute hypoxemia increases glucose utilization of the corona radiata to values equivalent to many gray matter structures, and leads to heterogeneous glucose metabolism in the cerebral cortex, but does not alter LCGU in other gray matter structures of newborn sheep. PMID- 2253326 TI - The development of ependyma in the human fetal brain: an immunohistological and electron microscopic study. AB - The stratified inner layer of the embryonic fetal brain, the ventricular zone (VZ), contains glial fibrillary acidic protein (GFAP)-positive cell bodies of radial glia. The adult cerebral ventricle is lined by a single layer of cuboidal, ciliated common ependymal cells which are, immunohistologically, GFAP negative. In late gestation, the ventricular lining is formed by tanycytes, ependymal cells with short, intensely GFAP-positive basal fibres. The development of ependyma was examined, morphologically and immunohistologically, in human fetal brain from between 11 weeks gestation to 6 months post-term to determine the relationship between the radial glia cell, tanycyte and common ependymal cell. This study was not able to show whether tanycytes were formed from radial glia or were formed from a previously uncommitted population of VZ cells. The study did show, however, that tanycytes probably mature into common ependymal cells following acquisition of cilia and loss of basal fibres. Electron microscopic data indicate that tanycytes have features suggestive of a secretory and/or transport function. PMID- 2253327 TI - Gradients of neurogenesis in possum neocortex. AB - Gradients of neurogenesis in neocortex of the brushtailed possum were determined with [3H]thymidine autoradiography, using data taken from 16 possums injected with [3H]thymidine between postnatal (P) days 5-68, and allowed to survive until brain cytoarchitecture was mature. Gradients of neurogenesis shown in neocortex were: (a) an inside-out radial gradient within cortical areas with neurogenesis beginning around P5 in layer 6 and concluding between 1 and 2 months later in layer 2, and (b) a single, simple, regional gradient across all neocortex. On the lateral surface of the hemisphere neurogenesis runs anteroventrolateral to posterodorsomedial, and on the medial surface neurogenesis runs anteroventral to posterodorsal. When plotted for the whole neocortex, the two regional gradients from the lateral and medial surfaces of the hemisphere are seen as parts of the one simple pattern. The time duration of neurogenesis in possum cortex is 1-2 months, and is similar to that seen in monkeys. PMID- 2253328 TI - Oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells from neonatal and adult rat optic nerve differ in their responsiveness to platelet-derived growth factor. AB - We have investigated, in vitro, the mitogenic responsiveness to platelet-derived growth factor (PDGF) of oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells isolated from adult rat optic nerve and their differentiation into oligodendrocytes. Progenitor cells from adult optic nerves differentiate into oligodendrocytes in a limiting concentration of foetal calf serum more slowly than in cultures of neonatal cells. Nevertheless, differentiation of oligodendrocytes from progenitors is nearly complete by 6 days in vitro, with 50% expressing galactocerebroside by 4-5 days. In these experiments, adult optic nerve cells were grown in medium containing PDGF, a potent mitogen for neonatal O 2A progenitor cells, and yet the decline in numbers of O-2A progenitor cells matches the rise in oligodendrocyte numbers. We suggest that this is because adult O-2A progenitor cells differ from their neonatal counterparts and do not show the same proliferative response in the presence of exogenous PDGF. We tested this hypothesis by a quantitative autoradiographic analysis of tritiated thymidine-labelled nuclei, comparing percentages of labelled adult and neonatal O 2A lineage glial cells in low-serum medium, in the presence of absence of PDGF, with their response to a monolayer of neonatal rat cortical type 1 astrocytes or astrocyte-conditioned medium. Whereas, adult O-2A progenitors responded to astrocyte monolayers and to conditioned medium from astrocyte cultures, there was no dose-dependent response to PDGF-BB over a wide range of concentrations. Antibodies to human PDGF neutralise the growth-promoting activity of astrocyte conditioned medium for neonatal O-2A cells but do not neutralise astrocyte conditioned medium stimulation of adult O-2A progenitor cells. This indicates that the principal astrocyte-derived growth factor(s) for adult O-2A progenitor cells is unlikely to be PDGF. PMID- 2253329 TI - Hippocampal neurotrophic factors influence the perikaryal size of septal acetylcholinesterase-containing neurons in culture. AB - The septal neurons were cultured under the following conditions: (1) treated with 7S nerve growth factor (NGF) (50 ng/ml); (2) grown with hippocampal cell conditioned medium supernatant; (3) cocultivated with hippocampal cells; (4) cocultivated with cerebellar cells; (5) no treatment. Acetylcholinesterase histochemistry was used to identify cholinergic cells after pretreatment with diisopropylfluorophosphate. The mean values of the perikaryal major axis and minor axis at day 14 of culture were significantly larger in septal cells cocultivated with hippocampal cells than in septal cells grown under other conditions. NGF-treated septal cells showed a smaller, but significant, increase in the mean value of the major axis of these neurons. PMID- 2253330 TI - Cellular and secreted lipoprotein lipase revisited. AB - Lipoprotein lipase (LPL) of adipose cells is present only in membrane compartments, mainly in the Golgi apparatus. LPL is a typical secretory protein which appears to be active as a homodimer. The process of LPL synthesis and maturation requires multiple steps. LPL is synthesized in the endoplasmic reticulum as an inactive monomer of Mr 51,000; a high-mannose, inactive monomer of Mr 55,500 is then formed. An active homodimer form, bearing two complex oligosaccharide chains per monomer of Mr 58,000, forms in the Golgi apparatus. This mature form, present in secretory vesicles, can be secreted constitutively or after exposure to heparin. A model is proposed in which LPL is present in secretory vesicles in a potentially active, condensed, or "polymerized" form. This model, which applies to various LPL-containing tissues in different species including human - would explain the "activation" of LPL. PMID- 2253331 TI - Phospholipases in biology and medicine. AB - Phospholipases, a group of enzymes that catalyze the hydrolysis of membrane phospholipids, are classified according to the bond cleaved in a phospholipid into PLA1 (EC 3.1.1.3), PLA2 (EC 3.1.1.4), PLB (EC 3.1.1.5), PLC (EC 3.1.4.3), and PLD (EC 3.1.4.4). This paper reviews source and structure of PLA2 and the involvement of PLA2 and PLC in several biological phenomena, such as, signal transduction, photoreception, biosynthesis of lung surfactant, sperm motility, and fertilization. New assays for PLA2 activity and concentration in biological fluids are discussed. Phospholipases are involved in many inflammatory reactions by making arachidonate available for eicosanoid biosynthesis. The determination of PLA2 activity and mass concentration in plasma is useful in the diagnosis and prognosis of pancreatitis and of septic shock. Naturally occurring phospholipase inhibitors, such as lipocortins act as second messengers in the anti-inflammatory response to steroids. Lipocortins may be valuable therapeutic agents, because they are more specific in their anti-inflammatory action than glucocorticoids; therefore, they are less likely to produce harmful side effects. PMID- 2253332 TI - Enzyme heterogeneity in the porphyrias. AB - The use of immunological methods for measuring enzyme mass has identified several varieties of porphyria in which the reduction of porphyrin enzyme activity is not accompanied by a corresponding change in the enzyme mass. Currently, acute intermittent porphyria and hepatoerythropoietic porphyria have exhibited this phenomenon. In porphyria cutanea tarda, it has recently been shown that the pattern of enzyme deficiency in erythrocytic and nonerythrocytic tissues does not strictly follow the inheritance pattern (familial and sporadic) previously described. Also, contrary to previous dogma, some cases of type 1 porphyria cutanea tarda appear to be positive for cross reactive immunological material (CRIM). PMID- 2253333 TI - Advances in the enzyme diagnosis of pancreatic diseases. AB - This paper reviews recent developments of analytical methods for the determination of alpha-amylase, of its isoenzymes, and of lipase. The evaluation of severity and etiology of acute pancreatitis by enzyme assays, e.g., pancreatic elastase 1, phospholipase A2, and routine enzymes are discussed. The limited significance of enzyme determinations as compared to imaging and endoscopic procedures for the diagnosis of chronic pancreatitis is demonstrated. Indirect "tubeless" tests for the evaluation of pancreatic exocrine insufficiency with respect to the secretion of chymotrypsin (chymotrypsin in stool and NBT-PABA test) and cholesterol esterase (pancreolauryl test) are reviewed. Finally, the superiority of morphologic investigations over biochemical tests for the timely detection of pancreatic carcinoma is shown. PMID- 2253334 TI - Rapid diagnosis of myocardial infarction and reperfusion by assay of plasma isoforms of creatine kinase isoenzymes. AB - Early, reliable detection of acute myocardial infarction and of coronary artery recanalization, in patients receiving thrombolytic agents, is essential to guide the course of therapy. Because the MM and MB isoenzymes of creatine kinase (CK) released from myocardium, undergo time-dependent removal of carboxyl terminal lysine residues from each monomer during exposure to circulating carboxypeptidase N, plasma profiles of the resulting isoforms are altered promptly and markedly after the release of new tissue isoenzymes. This paper reviews the results of experimental and preliminary clinical studies, showing the potential for rapid diagnosis of myocardial infarction and coronary artery recanalization by analysis of isoforms of CK isoenzymes in plasma. PMID- 2253335 TI - Red blood cell enzymes in the diagnosis of genetic disease. AB - Erythrocytes are uniform cells which contain only those proteins that are synthesized during the reticulocyte stage. The relationship of red cell enzymes to gene dosage and gene expression enables the use of red cell enzyme assays to determine the presence or absence of gene defects causing enzyme deficiencies leading to various metabolic diseases; in addition, the mode of inheritance of these defects can frequently be ascertained by analyzing red cell enzymes. However, indirect evidence favoring other enzyme deficiency states can sometimes be obtained from a study of red cell enzyme activities, because apparent enzyme deficiencies may result from the accumulation of inhibitory metabolites formed due to an enzyme deficiency in other tissues. The polymorphic expression of many red cell enzymes lends itself to biochemical analysis which can produce highly accurate and specific diagnostic information. PMID- 2253336 TI - Phenotypic and molecular biological analysis of human butyrylcholinesterase variants. AB - Our laboratory has recently shown that several variant forms of human butyrylcholinesterase, associated with unusual sensitivity to succinylcholine, are caused by specific mutations within the structural DNA coding for this enzyme. Atypical (dibucaine-resistant) butyrylcholinesterase is caused by a point mutation at nucleotide position 209(GAT-- greater than GGT), which changes aspartate 70 to glycine. One fluoride-resistant variant family has a point mutation at nucleotide 728(ACG-- greater than ATG), which changes threonine 243 to methionine. Another type of fluoride-resistant variant has a point mutation at nucleotide 1169(GGT-- greater than GTT), which changes glycine 390 to valine. One type of silent phenotype is due to a frame-shift mutation at nucleotide position 351(GGT-- greater than GGAG). A polymorphic site at nucleotide position 1615 (GCA/ACA), coding for Ala/Thr, accounts for the quantitative K-variant, which causes an approximate one-third reduction of activity, if Thr occupies that position at codon 539. Examples are given to illustrate the advantages of using a combination of the new DNA analytical techniques, including: the use of allele specific probes, with the standard serum cholinesterase phenotyping methods. More accurate typing of patients with certain variants is now possible; pedigree analysis will be aided by the improved methodology. PMID- 2253337 TI - Enzyme reagents from unusual sources. AB - Although microbes are frequent sources of clinically useful enzymes, there are certain biocatalysts which appear to be enriched in, or more naturally available from nonmicrobes. This paper highlights several of these enzyme reagents, and illustrates their potential or actual clinical diagnostic uses. These reagents include: an enzyme extract containing both glucose oxidase and mutarotase activities from peppers; a bilirubin-degrading enzyme from orange peels; a gentisic acid metabolizing activity from onions; and enzymes from snails which catalyze the detoxification of cyanide by divergent mechanisms. PMID- 2253338 TI - Detection techniques for immunoassay and DNA probing applications. AB - A brief review of the major detection systems used in the field of biotechnology is presented. The focus is on immunoassay and DNA probing applications and on systems that show promise of extreme sensitivity. Specific examples are discussed to illustrate approaches which introduce chemical, enzymatic, or exponential amplification. The author's projections for the next 5-10 years in this field are expressed. PMID- 2253340 TI - Does CLIA '88 mandate regulation of physician utilization of laboratory testing? PMID- 2253339 TI - The eicosanoids: a historical overview. AB - Eicosanoids are biologically active compounds derived from 20 carbon unsaturated fatty acids, among which arachidonic acid is a substrate of particular importance. The history of the eicosanoids dates back to the thirties, when new biologically active compounds were found in human seminal plasma. These "prostaglandins" were purified, and their structures and mechanisms of biosynthesis were elucidated in the early sixties. Other eicosanoids, including thromboxane A2, a potent platelet aggregating agent, and prostacyclin, an antagonist to thromboxane A2, were discovered in the seventies. The inhibitory actions of acetylsalicylic acid on eicosanoid synthesis were also uncovered at this time. In 1979, a new metabolic sequence leading to the synthesis of a new group of eicosanoids, called leukotrienes, was reported. The leukotrienes have several biological activities, including the mediation of bronchoconstriction in allergic response. The eicosanoids comprise a diverse group of biologically active compounds; many of these arise from arachidonic acid, and are associated with injury, allergic responses, and platelet aggregation. PMID- 2253342 TI - Clinical laboratory regulation under the Clinical Laboratory Improvement Amendments of 1988: can it be done? AB - This report examines logical but not yet widely recognized ramifications of the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88), federal legislation that will require certification of all laboratories examining human specimens. Examination of the CLIA'88 committee reports and committee hearings suggest that more than the conventional approach to laboratory standards will be needed to meet the public's expectations as articulated by our elected representatives. The conventional approach to clinical testing standards seeks to assure quality by regulating the laboratory analytical process. However, little empirical evidence is available to support or refute this model, which has been used during the past 25 years. One alternative paradigm for laboratory standards is an approach that examines the total laboratory testing process, including the selection, ordering, and interpretation of the test as well as the laboratory analysis per se. The history of controversy over laboratory standards--especially personnel standards, the glacial federal regulatory rulemaking process, public expectations of fail safe technology, among other factors--suggests the implementation of CLIA'88 will be a lengthy and vigorously debated contest. The risk of a test is seldom inherent in the test itself, but rather is a function of the context in which the test is being used to provide information for medical decision making. Our premise is that diagnostic tests must be examined in the context of the laboratory testing situation. We suggest that now is the appropriate time for laboratory professionals, practicing physicians, and the public to abandon conventional thinking regarding clinical laboratory standards. We believe that CLIA'88 reflects a shift in public expectations toward fail-safe laboratory testing and the need for additional government oversight in laboratory test quality. If these new expectations persist, CLIA'88 represents a potential landmark in the course of federal authority and the practice of medicine in the United States. PMID- 2253341 TI - The unique lipoprotein(a): properties and immunochemical measurement. AB - Lipoprotein (a) [Lp(a)] represents a class of lipoprotein particles defined by the presence of apolipoprotein(a), a unique glycoprotein linked by a disulfide bond to apolipoprotein B-100 to form a single macromolecule. Apolipoprotein(a) is formed by three different structural domains having high amino acid sequence homology with plasminogen. One of the domains, called kringle 4, is present in multiple copies, the number of which varies and is genetically determined. This accounts for the size heterogeneity of apolipoprotein(a) and thus of Lp(a). Because high concentrations of Lp(a) are associated with atherosclerotic cardiovascular and cerebrovascular disease and may inhibit fibrinolysis, interest in measuring Lp(a) has increased considerably, leading to a rapid development of commercially available immunoassays for the measurement of Lp(a) in human plasma. However, the immunochemical measurement of Lp(a) has several peculiar problems in addition to those encountered by the measurements of other apolipoproteins. The major problems that need to be carefully evaluated are (a) the structural complexity and heterogeneity of Lp(a), (b) the homology of apolipoprotein(a) with plasminogen, (c) the lack of standardization of the methods, and (d) the lack of a common means of expressing the Lp(a) values. PMID- 2253343 TI - Direct chemiluminescence immunoassay of estradiol in saliva. AB - A sensitive and simple direct solid-phase chemiluminescence immunoassay is described for estradiol in saliva. In this assay, a second antibody is bound to the wells of microtiter plates. Either buffer with standards or saliva (100 microL) is incubated in these wells with monoclonal anti-estradiol antibody and with estradiol-isoluminol conjugate. Incubation time is 2 h. Chemiluminescence of the bound fraction is measured in a manually operated luminometer (Biocounter). The assay has a detection limit of 3.8 pmol/L; analytical recovery of added estradiol is 96.8% (SD 7.0%); within- and between-assay CVs range between 2.5% and 12.7%. Forty unknown saliva samples can be assayed and results calculated within 4.5 h. Results of a slightly modified procedure-with black microtiter plates and a prototype of an automated plate reader (Luminoskan)--compare well with those of the described method (r = 0.97). Because steroid-binding globulins have been found in saliva, the effect of displacing agents on the results of the direct chemiluminescence assay is described. PMID- 2253344 TI - Concentrations of apoprotein CII, CIII, and E in total serum and in the apoprotein B-containing lipoproteins, determined by a new enzyme-linked immunosorbent assay. AB - We describe a new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of apoprotein (apo) CII, CIII, and E in total serum as well as in apo B-containing lipoprotein particles. To validate this ELISA technique, we studied several aspects of the assay: its specificity, the influence of the conditions of conservation of plasma and of lipoprotein fractions, the effect of delipidation, and its reproducibility. We measured the concentrations of apo CII, CIII, and E in total serum and in apo B-containing lipoproteins from a pool of normal sera and in sera from 75 healthy subjects. After sequential ultracentrifugation, the content of apo CII, CIII, and E in the major lipoprotein fractions was also determined. Total serum or plasma could be stored at -20 or 50 degrees C for at least six weeks and the isolated lipoprotein fractions for as long as four weeks, which suggests a protective effect of total serum on lipoprotein particle structure. Advantages of this ELISA include (a) its specificity, sensitivity, and reliability; (b) better discrimination than determination of total serum apoprotein; (c) easier application and greater rapidity; and (d) the possibility of application to population screening. PMID- 2253345 TI - Development and comparative evaluation of immunoblot assays for detecting autoantibodies to Scl 70 and Jo 1 antigens in serum. AB - We developed rapid 24-h immunoblot assays for detecting autoantibodies to Scl 70 and Jo 1 antigens in serum. In comparative studies, we evaluated the analytical sensitivity of the immunoblot assays and commercial immunodiffusion assays for anti-Scl 70 and anti-Jo 1 autoantibodies with the use of positive control sera, and compared the frequencies of positive and negative results in a group of 116 sera, including specimens from 34 healthy controls and 82 patients with various connective-tissue diseases. The immunoblot assays were greater than 100-fold more sensitive than immunodiffusion for detecting both autoantibodies. Despite greater analytical sensitivity, there were no false-positive results by the immunoblot assay for anti-Scl 70 or anti-Jo 1 autoantibodies in sera from either the controls or the patients. The diagnostic sensitivity of the immunoblot assay for anti-Scl 70 autoantibodies in patients with scleroderma was greater than that of the immunodiffusion assay, 70% vs 20%, and was equivalent in patients with polymyositis, 43%. We conclude that rapid immunoblot assays for anti-Scl 70 and anti-Jo 1 autoantibodies are superior to immunodiffusion assays for clinical use and are suitable for routine use in the clinical laboratory. PMID- 2253346 TI - Kinetic measurement of bicarbonate in serum by thiocyanate inhibition of wheat germ phosphoenolpyruvate carboxylase. AB - We describe a kinetic enzymic method for serum bicarbonate analysis, using wheat germ phosphoenolpyruvate carboxylase (EC 4.1.1.31) coupled through oxaloacetate reduction with NADH in the presence of malate dehydrogenase (EC 1.1.1.37). Inhibition with potassium thiocyanate yielded first-order kinetics with respect to bicarbonate over the concentration range of 0-45 mmol/L. The inhibitor was chosen by evaluating reaction data in the presence of different anions, with use of a monoexponential model. Criteria for first-order kinetics included a constant reaction half-life over the concentration range and SDest for the model comparable with the magnitude of spectrophotometric noise. We compared our kinetic method (y) with an automated ion-selective electrode method (x), obtaining the regression relationship y = 0.97x + 1.2 mmol/L (r = 0.991; n = 77; mean = 25.5 mmol/L; y = 25.3 mmol/L). Within-run precision from duplicates was 3.1% (mean = 25.2 mmol/L; n = 72). Total analytical precision (n = 12) was 9.4% (mean = 15 mmol/L) for the low control and 4.3% (mean = 32 mmol/L) for the high control. We conclude that the kinetic assay allows use of large serum-to-reagent ratios (1:100) and smaller amounts of NADH than an equilibrium assay. The assay is suitable for automated kinetic analysis. PMID- 2253347 TI - Automation of specific human gene detection. AB - An instrument/chemistry system is described that automates a new chemical procedure functionally equivalent to Southern blotting. A fluorescence gel scanner that detects migrating DNA fragments in real-time analyzes the samples produced by a prototype liquid-handling instrument that automates a solution phase hybridization/solid-phase capture chemistry for DNA analysis. The combination of this chemistry, the gel scanner, and robotic automation eliminates the tedium encountered in traditional manual methods for specific gene detection and reduces analysis time from days to hours. Restriction fragment lengths are measured with high precision by comparison with in-lane standards to minimize effects attributable to migration anomalies. The utility of this automated system is demonstrated by executing a clinical research application involving hybridization to a multi-copy repeat sequence on the Y chromosome and its detection. PMID- 2253348 TI - Fluorometric determination of carnitine in serum with immobilized carnitine dehydrogenase and diaphorase. AB - A fluorometric flow-injection method for determining carnitine with use of immobilized enzymes carnitine dehydrogenase (EC 1.1.1.108) and diaphorase (EC 1.8.1.4) was developed and applied to the assay of carnitine in serum of patients treated with valproic acid. After fractionation and hydrolysis of carnitines in serum samples by perchloric acid and potassium hydroxide, liberated carnitine was converted to resorufin by immobilized carnitine dehydrogenase and diaphorase in the presence of beta-NAD+ (1.0 mmol/L), resazurin (12.5 mumol/L), and Tris acetate (0.6 mol/L, pH 9.0) at 37 degrees C. The fluorescence intensity of resorufin was monitored at lambda Ex 560 nm and lambda Em 580 nm. The calibration curve was linear for carnitine amounts from 0.1 to 1.0 nmol. Quantitative analytical recovery and satisfactory within- and between-run imprecision of carnitine in each carnitine fraction were obtained. Interference by bilirubin, serum albumin, and hemoglobin was negligible. Carnitine deficiencies were detected in about 20% of the valproic acid-treated patients (n = 198). The present method should be useful for monitoring carnitine deficiencies in clinical laboratories. PMID- 2253349 TI - Assay of functional activity of alpha 1-antichymotrypsin in plasma. AB - We introduce a novel assay for measuring active alpha 1-antichymotrypsin (alpha 1X) in human plasma. The assay works on the principle that cathepsin G, immobilized in microtiter plates, preferentially binds alpha 1X, which then can be specifically quantified immunologically. alpha 1X activity can be detected even after 50,000-fold dilution of normal plasma. A linear range was defined for reproducible quantification. There was no interference by alpha 1-proteinase inhibitor or alpha 2-macroglobulin. The assay is designed to detect conditions having decreased alpha 1X activity to further elucidate the biological function of this prominent acute-phase protein. PMID- 2253350 TI - Polyol concentrations in serum during hemodialysis. AB - Polyol concentrations were determined by selected-ion monitoring in 10 sample sets taken before dialysis and hourly for 4 h during dialysis. Predialysis concentrations (mumol/L) exceeding the upper limit of normal (mean + 2 SD; n = 33) were found for erythritol (25.4-59.0), threitol (11.5-46.7), and arabinitol (21.0-49.3) in all 10 cases; mannitol (2.7-62.0) in nine cases; and xylitol (0.7 1.3) in eight cases. Concentrations of adonitol, galactitol, and sorbitol were all within normal limits. During dialysis, the concentration of six polyols decreased by approximately 50%, but there were no significant changes for xylitol and adonitol. Erythritol, threitol, and arabinitol concentrations remained more than double the upper limit of normal in all patients after 4 h of dialysis. High residual concentrations were found for mannitol (seven cases) and xylitol (six cases). The results suggest fundamental differences in the homeostasis as well as the dialyzability of different polyols. The potential toxic significance of the high residual concentrations after a 4-h dialysis needs to be investigated. PMID- 2253351 TI - Apolipoprotein E polymorphism determined by restriction enzyme analysis of DNA amplified by polymerase chain reaction: convenient alternative to phenotyping by isoelectric focusing. AB - Three common alleles determine six apolipoprotein E (apo E) phenotypes that are associated with variations in serum cholesterol in the population. This genetic variation results from single nucleotide alterations at two DNA loci encoding the amino acid residues 112 and 158 of apo E. We compared results of apo E phenotyping carried out by isoelectric focusing with those of apo E genotyping accomplished by direct DNA analysis. In the latter, the target DNA was amplified by the polymerase chain reaction (PCR) and subsequently analyzed by digestion with the restriction enzyme Hha I, followed by polyacrylamide gel electrophoresis of the cleavage products. With one exception, these two techniques yielded similar results from all 40 samples tested. In addition, a rare variant form of apo E (phenotype E1) was analyzed separately and incorrectly diagnosed as E2 by the Hha I digestion method; the anticipated mutation in the codon 127 was, however, confirmed by demonstration of a new Taq I restriction site in this variant gene. These data confirm that the common isoforms of apo E usually arise from genetic variation of the codons 112 and 158 and demonstrate the feasibility of the PCR technique in apo E genotyping. PMID- 2253352 TI - Diagnosis of ectopic pregnancy by the rate of increase of choriogonadotropin in serum: diagnostic criteria compared. AB - We compare three methods for using the rate of change of human choriogonadotropin (hCG) concentration in serum to diagnose ectopic pregnancy. With Method I, the lower limit for the rate of increase of serum hCG in normal pregnancy is 66% per 48 h. With Method II, a different lower limit of normal is specified for each of four discrete sampling intervals of hCG. With Method III, the lower limit of normal is determined by a continuous discriminant function of the initial hCG concentration. If the initial hCG concentration is less than or equal to 2000 int. units/L (Second International Standard), all three methods have acceptable diagnostic efficiencies, and there are no statistically significant differences among conclusions from the methods. None of the three methods performs satisfactorily if the initial hCG concentration is greater than 2000 int. units/L. We recommend Method I because it is simpler than the other two. PMID- 2253353 TI - Proficiency testing for creatine kinase isoenzyme CK-2 (CK-MB) in Ontario. AB - Three surveys of the measurement and interpretation of creatine kinase (CK; EC 2.7.3.2) isoenzyme 2 (CK-MB) were conducted in Ontario, Canada, in 1989. Of the clinical laboratories participating, 66% used immunological methods and 24% used electrophoretic methods. Although reference ranges and interpretative routines varied widely, 95% of the laboratories reported correct interpretations for 10 of the 15 vials tested. The only major problems occurred with samples with very low total CK activity. Within-survey duplicate results compared well, and 89% of the laboratories had consistent between-survey results, even for specimens with low total CK activity. Errors were proportional to the frequency of use of the different analytical methods. The lyophilized testing material gave higher results with methods for measuring the mass of CK-2, suggesting that the material contained inactive but immunologically intact CK-2. The surveys indicate that laboratories should review their protocols for measuring CK-2 when only a single sample from the patient is available. PMID- 2253354 TI - Increased circulating concentrations of interleukin 2 receptor during rejection episodes in heart- or kidney-transplant recipients. AB - Concentrations of interleukin 2 receptor (sIL-2R) have been suggested as a marker of rejection episodes after organ transplantation. To evaluate the analytical performance of a "sandwich-type" enzyme immunoassay method for sIL-2R and to verify whether increased concentrations of sIL-2R might be a useful marker of allograft rejection, we quantified sIL-2R in serum samples from heart- or kidney transplant patients. The mean (+/- SD) pre-transplant value of sIL-2R (592 +/- 209 kilo-units/L) in heart-transplant patients was significantly higher (P less than 0.01) than that observed in controls (350 +/- 101 kilo-units/L). After heart transplantation, the concentrations of sIL-2R slowly decreased to baseline in successfully treated patients but increased significantly (1129 +/- 215 kilo units/L; P less than 0.01) during acute rejection crisis. However, severe infections were also associated with a significant increase of sIL-2R, so the sIL 2R test is not specific for allograft rejection. The mean pre-transplant concentration of sIL-2R was also increased (1943 +/- 878 kilo-units/L) in 26 renal-transplant patients; after transplantation, this value returned to normal, as did that for creatinine, but persisted steadily high in five patients who experienced acute tubular necrosis. In this group of patients, the sIL-2R concentration increased by 1.5- to fourfold, both during acute rejection episodes and in clinically evident infection; thus measurement of creatinine and sIL-2R concentrations can help to distinguish between rejection, infection, and cyclosporine toxicity. In two episodes of mild cyclosporine-induced nephrotoxicity, we observed slight increases in serum creatinine (which returned to baseline when the cyclosporine dose was decreased) not associated with an increase in sIL-2R. We conclude that systematic monitoring of sIL-2R together with other biochemical and clinical markers may be useful in the management of kidney-transplant patients. PMID- 2253355 TI - Insufficient accuracy and specificity of polyanion precipitation methods for quantifying low-density lipoproteins. AB - Recently, polyanion precipitation assays for low-density lipoprotein (LDL) cholesterol have been found to underestimate their analyte in normolipidemic samples (Siekmeier et al., Clin Chim Acta 1988;177:221-30). Therefore, accuracy, specificity, and interference by nonesterified fatty acids have been studied for three precipitants (obtained by heparin, dextran sulfate, or polyvinyl sulfate precipitation). At normal concentrations of LDL, precipitation is incomplete, whereas it is nearly quantitative at high concentrations of LDL. The polyvinyl sulfate reagent markedly responds to variations in the amount of non-LDL protein present in the precipitation mixture. In the dextran sulfate and the polyvinyl sulfate method, but not in the heparin method, the percentages of LDL precipitated notably increase as the concentration of the polyanion compound is decreased. In either assay, very-low-density lipoproteins, but not high-density lipoproteins, are significantly coprecipitated (dextran sulfate 28%, polyvinyl sulfate and heparin 66%) in a concentration-independent fashion. Increased concentrations of nonesterified fatty acids markedly interfere with the dextran sulfate and polyvinyl sulfate assay, but do not much affect results with the heparin reagent. PMID- 2253356 TI - Determination of carrier status in Duchenne and Becker muscular dystrophies by quantitative polymerase chain reaction and allele-specific oligonucleotides. AB - Detection of carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), in the deletion cases, involves calculating gene dosage from Southern blots. We show that the analysis of dosage can also be made from the polymerase chain reaction (PCR) with use of allele-specific oligonucleotides (ASOs). The deletion-prone exons are amplified, transferred to a membrane, and hybridized with ASOs complementary to the exons; the autoradiographic bands are then quantified with a densitometer. After determining the quantitative conditions of the amplification reaction, we were able to identify deletions in a DMD/BMD carrier female. The determination of carrier status via PCR removes several of the technical limitations of Southern analysis and is also cost- and labor-effective. PMID- 2253357 TI - Determination of reference values for serotonin concentration in platelets of healthy newborns, children, adults, and elderly subjects by HPLC with electrochemical detection. AB - We adapted a high-performance liquid chromatographic method with electrochemical detection (Clin Chim Acta 1984;139:1-12) to the determination of platelet serotonin. We used this method to determine platelet serotonin reference values in a healthy population, measuring platelet serotonin concentration in the following subjects: 31 newborns (16 girls, 15 boys); 41 children (11 girls, 30 boys), ages 20 months to 15 years; 56 adults (26 women, 30 men), ages 20 to 58 years; and 20 elderly subjects (16 women, four men), ages 65 to 94 years. There was no significant difference in platelet serotonin concentration between sexes in each age group. However, significant changes (P less than 0.001) were observed between the newborns (mean +/- SD: 1.67 +/- 0.74 nmol/10(9) platelets) and the children (4.09 +/- 1.04) or the adults (3.81 +/- 0.87). Moreover, the platelet serotonin concentration in the elderly subjects (2.57 +/- 1.12) was significantly (P less than 0.001) lower than in the adults and children and significantly higher (P less than 0.01) than in the newborns. Such age-related differences must be taken into consideration when data from neurological or psychiatric patients and control subjects are compared. PMID- 2253358 TI - Monitoring free digoxin instead of total digoxin in patients with congestive heart failure and high concentrations of digoxin-like immunoreactive substances. AB - Digoxin-like immunoreactive substances (DLIS) are present in patients with conditions associated with volume expansion (including hypervolemic hypertension, renal failure, and liver failure) and in pre-eclampsia and premature birth. These strongly-protein-bound substances cross-react with anti-digoxin antibodies and cause falsely increased measured concentrations of digoxin in serum. Patients with congestive heart failure (CHF) often have volume expansion and are receiving digoxin therapy. They are also very sensitive to digoxin toxicity and have a very narrow therapeutic range (1.0-1.9 nmol/L). We found monitoring the concentrations of free digoxin (in protein-free ultrafiltrates) helpful in eliminating the interferences of DLIS in CHF patients. DLIS concentrations were measured by fluorescence polarization assay. Concentrations of DLIS were detectable in significantly more (58.3%) of the 12 CHF patients (group A) who were not receiving digoxin than in the 22 normal volunteers tested (13.6%) (P less than 0.05 by both chi-square and Fisher's exact test). Protein-free filtrates from patients or normal volunteers did not show any measurable DLIS activities. We also determined the concentrations of total and free digoxin in 12 patients with CHF who were receiving digoxin (group B) and compared the results with those for 22 patients receiving digoxin without the diagnosis of CHF or any known pathological conditions that could increase DLIS concentrations. The ratio of free to total digoxin in patients in group B was significantly lower (mean = 52.8%, SD 10.2%) than in those receiving digoxin (mean = 72.7%, SD 6.5%) for other reasons (independent two-tailed t-test, P less than 0.05). PMID- 2253359 TI - Simplified fluorometric assay of total selenium in plasma and urine. AB - We describe here a single-tube assay that may be applied to the whole range of selenium status in adult and pediatric patients, including depletion during parenteral or other nutrition. A specimen or aqueous standard, 100 microL, is digested with 0.5 mL of HNO3/HCIO4 (4/1 by vol, at 190 degrees C for 90 min), reduced with 0.5 mL of concentrated HCI (150 degrees C, 30 min), and complexed with 0.5 mL of 6.3 mmol/L 2,3-diaminonaphthalene (DAN) reagent in the presence of EDTA (60 degrees C, 30 min). The resulting fluorophore is extracted into cyclohexane and its fluorescence measured (excitation at 366 nm; emission at 544 nm). It is not necessary to control pH during the complexing step or to protect the DAN from light. The limit of detection of selenium is 10 micrograms/L (0.126 mumol/L); linearity of results extends to 2000 micrograms/L (25.3 mumol/L). Between-batch precision is 5%, analytical recovery 90%-96%. Performance is good as tested against Reference Materials and by participation in a National Quality Assurance Scheme. PMID- 2253360 TI - Centrifugal ion-selective electrode system for potassium in whole blood. AB - We describe a novel ion-selective electrode (ISE) system that can be used in the Abbott Vision analyzer. A reusable sensor pack and a disposable test pack have been miniaturized to approximately the size and weight of a conventional Vision test pack, thus eliminating the need for a separate ISE module. The sensor pack contains a fluid path, battery-powered electronics, and screw-in electrodes. The test pack contains separate chambers and fluid channels for a blood specimen and two aqueous calibrators. During a run, plasma is separated from blood cells and is moved sequentially, along with the two calibrators, into and out of the sensor pack by centrifugal force. Each run includes checks for electromechanical integrity, fluid contamination, calibration slope and intercept, and specimen hemolysis. The system operates with CVs of less than 2% and gives results that correlate well with those by flame photometry and direct ISE methods. Either skin puncture or venipuncture whole blood can be assayed, as well as serum or plasma. PMID- 2253361 TI - Semi-automated colorimetric method for measuring glycohemoglobin, with reduction of nitroblue tetrazolium, evaluated. AB - I evaluated a semi-automated method for measuring glycohemoglobin via reduction of nitroblue tetrazolium by acetone-extracted globin. The simultaneous measurement of glycated protein and total protein with the Roche Mira S analyzer showed good analytical precision (between-batch CV 3.5%-8.5%). Correlation of results (y) with those by a boronate affinity chromatography method (x) gave a regression line of y = 2.0x + 5.9 for samples from patients attending a diabetic outpatient clinic. I also studied reaction kinetics; chloromercuribenzoate concentration, sample volume, and detergent concentration affect the reaction, probably by modulating the reduction of dye by globin-thiol groups. PMID- 2253362 TI - Relationship between delta checks for selected chemistry tests. AB - The correlation between delta differences for 20 serum chemistry tests was calculated for 2400 samples from 288 patients. There were 12 pairs of chemistry tests for which correlation coefficients of the delta checks exceeded 0.25; aspartate aminotransferase and alanine aminotransferase had the highest Pearson correlation coefficient, 0.915. The highest negative, indirect, correlation was between the delta checks of bicarbonate and chloride (-0.219). The relationship between delta differences may be used as a quality-control technique to detect analytical errors. PMID- 2253363 TI - Concentrations of total homocysteine in plasma in chronic renal failure. PMID- 2253364 TI - Reference ranges for insulin-like growth factor-1 in healthy children and adolescents, determined with filter-paper blood specimens. PMID- 2253365 TI - Improved materials for long-term quality-control assessment of erythrocyte folate analysis. PMID- 2253366 TI - Interference by newer cephalosporins in current methods for measuring creatinine. PMID- 2253367 TI - Biological variation of Zn, Cu, and Mg in serum of healthy subjects. PMID- 2253368 TI - Effect of storage conditions on salivary sialic acid concentrations. PMID- 2253369 TI - Different sensitivity to anti-triiodothyronine autoantibodies of two direct radioimmunoassays of free triiodothyronine. PMID- 2253370 TI - Competitive immunochemiluminescence assay for measuring lutropin in urine. PMID- 2253371 TI - Adenosine deaminase in pregnancy serum. PMID- 2253372 TI - Rhabdomyolysis secondary to lovastatin therapy. AB - We report a case of lovastatin-induced rhabdomyolysis and resulting life threatening renal failure. Lovastatin, a hypocholesterolemic agent, decreases endogenous cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88). This agent has been implicated in causing rare serious side effects in various clinical settings; however, the mechanism of these adverse reactions is not understood. The clinical course of our patient was characterized by profound muscle weakness with marked increases in serum creatine kinase and myoglobin. Light- and electron-microscopic studies of skeletal muscle of our patient demonstrated a noninflammatory myopathy suggestive of ongoing rhabdomyolysis with vacuolization and focal degeneration of myocytes. The patient's symptoms and the laboratory values referable to rhabdomyolysis resolved after discontinuation of the drug. We speculate that the rhabdomyolysis was due to mitochondrial damage secondary to inadequate synthesis of coenzyme Q and heme A, members of the electron-transport system of the inner mitochondrial membrane. PMID- 2253373 TI - Imprecision of the Stratus immunoassay system for free thyroxin underestimated. PMID- 2253374 TI - Measuring cholesterol without interference from lipemia. PMID- 2253375 TI - Determination of glycated protein by agarose gel electrophoresis with nitroblue tetrazolium staining. PMID- 2253376 TI - Guidelines for out-of-hours clinical chemistry investigations. PMID- 2253377 TI - Progressive changes in glycine and glycine derivatives in plasma and cerebrospinal fluid after transurethral prostatic resection. PMID- 2253378 TI - What's in a name? PMID- 2253379 TI - Standardization for the reporting of nasopharyngoscopy and multiview videofluoroscopy: a report from an International Working Group. AB - A multidisciplinary International Working Group of scientists was assembled to address the question of standardizing reporting techniques for multiview videofluoroscopy and nasopharyngoscopy, the generally accepted standards for direct observation of the velopharyngeal valve. This report is a first attempt to propose standards while seeking feedback from the readership in order to further develop a common methodology. PMID- 2253380 TI - Effect of timing and method of cleft palate repair on dental arches at the age of three years. AB - The purpose of this study was to compare the influence of two different ages at the time of palatal closure and two surgical methods on the size of the dental arches at the age of 3 years in children, with CP, UCLP, and BCLP. In 88 children the one-stage palatal closure had been performed at the age of 1.8 years and in 92 children at the age of 1.1 years. In both groups palatal surgery had been performed with a V to Y push back procedure (Veau-Wardill-Killner) or with the Cronin modification. Dimensions of the maxillary arch in both groups at age 3 were smaller than in noncleft children, but the timing of palatal closure did not affect arch dimensions in children with CP, UCLP, or BCLP. Arch dimensions at 3 years of age were not related to the method used in palatal closure. PMID- 2253381 TI - Evaluation of unilateral cleft lip and palate treatment: long term results. AB - Fifty-seven consecutive complete unilateral cleft lip and palate patients were followed longitudinally from birth to 21 years of age. All patients were operated with the same primary surgical procedures. Reevaluation at age 21 with respect to speech, dental condition, need for secondary surgery, and skeletal and soft tissue facial growth was completed. Speech results indicated that 13 patients (23 percent) had required a pharyngeal flap, and that at age 21 only one patient still had unacceptable speech. The majority of patients had slight speech disturbances related to articulation and voice quality. Fifty-one patients had acceptable occlusion following orthodontic treatment, twenty-two patients (39 percent) without need for prosthodontic treatment of the cleft area. Secondary surgery for correction of nasal deformities was required for fifty-two patients. Growth analysis demonstrated deficiency in growth; however, normal and acceptable profiles were obtained in 50/57 of the patients. PMID- 2253382 TI - Trigonocephaly: clinical and cephalometric assessment of craniofacial morphology in operated and nontreated patients. AB - Craniofacial parameters were studied clinically and by cephalometry in 11 trigonocephalic patients from infancy to 4 years of age. Six of the most severe patients had surgery between 6 and 18 months of age. Analysis of morphology indicated that bony interorbital distance was reduced in patients selected for surgery and hypotelorism persisted at final examination. All patients demonstrated orbital width measurements above the mean for the norm, while orbital height was essentially normal. All but one of the patients had a variably prominent forehead bony ridge that was eliminated or reduced as a result of surgery and/or growth. However, the forehead of most patients, whether operated or not, was too narrow when compared to normal skulls. Thus, although some of the striking features of trigonocephaly are eliminated, minor characteristics of the anomaly still persevere at 4 years of age. PMID- 2253383 TI - Audiologic management of bilateral external auditory canal atresia with the bone conducting implantable hearing device. AB - The hearing impairment associated with congenital external auditory canal atresia has been managed with early bone conduction hearing aid placement and surgical reconstruction in selected patients. However, many patients do not wear a bone conduction hearing aid because of physical or social considerations and surgical reconstruction of the external auditory canal and middle ear may be difficult or contraindicated. This report details the use of implantable bone conducting hearing devices in five children with bilateral external auditory canal atresia. Each patient had bilateral conductive hearing impairment with normal bone conduction thresholds. Four of the five patients had associated craniofacial anomalies including three cases of microtia. The average preoperative sound field speech reception threshold improved from 63 dB to 13 dB with the implant. Patients experienced a definite preference for the implanted hearing device over the bone conduction hearing aid. PMID- 2253384 TI - The morphometry and three-dimensional structure of the adult eustachian tube: implications for function. AB - An accurate description of the functioning Eustachian tube (ET) requires a thorough knowledge of the anatomic relationships of its components. To this end, 15 "normal" adult ETs were obtained, sectioned, and stained with hemotoxylin eosin. Descriptive and quantitative data of ET structures and their relationships were obtained. Eustachian tube length was normalized and comparisons between specimens made. This analysis suggests (1) in its midsection the cartilage is loosely attached to the cranial base; (2) the deep portion of the tensor veli palatini (TVP) originates from the lateral lamina and the fibrous portion of the lateral membraneous wall; and (3) the levator veli palatini (LVP) can interact with the ET primarily via the elongated medial lamina in the anterior portion of the ET. These observations suggest the ET is opened by a medial rotation of cartilage effected primarily by the TVP, but aided anteriorly by the LVP. PMID- 2253385 TI - Individual skull model fabrication for craniofacial surgery. AB - The purpose of this report is to describe a milling procedure for the fabrication of skull models from 3-D CT data. Data from computer tomographic cuts are transferred to a computer and stored. Model fabrication takes place using high quality styrodur that is shaped with a high speed milling device. This allows the modeling of an individual life size skull in its skeletal as well as in its soft tissue contours. Smaller bone pieces and areas can be enlarged separately up to eight times normal size for better visualization. Planning and simulation of craniofacial surgery in three dimensions is possible, and bone implants or alloplastic biomaterials can be modeled for implantation. PMID- 2253386 TI - Dexamethasone receptor levels in palatal and lung fibroblasts of adult A/J and C57BL/6J mice: relationship to glucocorticoid-induced cleft palate. AB - Glucocorticoid-induced cleft palate (CP) has been used as an animal model for hormonal teratogenesis. In mice, the susceptibility to glucocorticoid-induced CP varies with the strain, A/J being very sensitive and C57/BL6J relatively resistant. Studies in adult and embryonic murine tissues have attempted to correlate the number of glucocorticoid receptors and CP susceptibility, with conflicting results. The relative quantities of dexamethasone receptors were now studied in established palatal and lung fibroblast cell cultures obtained from adult C57 and A/J mice. A rapidly saturable, stable binding system was demonstrated. Scatchard plots were linear indicating a single class of high affinity receptors. The glucocorticoid receptor number ranged from 6.2 x 10(-16) mole/microgram prot to 8.6 x 10(-16) mole/microgram prot, while the KD varied from 1.0 x 10(-8) M to 2.8 x 10(-8) M. The differences in receptor characteristics between murine strains were not significant (p greater than 0.05). The absence of a difference in receptor number between the two strains may reflect the limitation of fibroblast cell culture in assessing glucocorticoid binding in vivo. Alternatively, if a difference in palatal dexamethasone receptor levels between mice strains exists, it may occur only in the embryo. PMID- 2253387 TI - The aerodynamic characteristics of speech produced by normal speakers and cleft palate speakers with adequate velopharyngeal function. AB - Pressure-flow data were obtained on 20 noncleft adults with normal speech and 26 adults with repaired cleft palate. All subjects had adequate velopharyngeal function as determined by preliminary aerodynamic assessment. Subjects were considered to have adequate closure if they had velopharyngeal areas no greater than 0.049 cm2 during production of /p/ in the word "hamper." Although the subjects in both groups demonstrated velopharyngeal adequacy, the subjects with cleft palate produced speech with significantly less nasal airflow. In addition, their intra-oral pressure curve was shifted forward in time. These differences suggest that speakers with cleft palate and adequate velopharyngeal function make certain compensatory adjustments that may be necessary because of differences in velopharyngeal movement capabilities. The potential significance of this for treatment planning is discussed. PMID- 2253388 TI - The tongue flap: placement and fixation for closure of postpalatoplasty fistulae. AB - A tongue flap is frequently used for closure of fistulae following cleft palate repair. Early tongue flap dehiscence is a troublesome complication. While the tongue flap is a very effective means of functionally obliterating the transpalatal oronasal opening, the final appearance of the repair leaves much to be desired. More often than not, the tongue tissue appears bulky and unnatural in the roof of the mouth. A method is described that overcomes the problem of flap detachment during the early postoperative period by suspending and supporting the tongue pedicle with a palatal sling. On peroral view, the repaired area has a better appearance when the tongue flap lines the nasal side rather than the oral side as in conventional procedures. PMID- 2253389 TI - Webbing of the pharyngeal recess in adults with cleft palate. AB - The limited literature on the lateral pharyngeal recess of Rosenmuller and the various presentations of pharyngeal webbing are reviewed. Webbing across the lateral pharyngeal recess is described in 28 of 31 adults with cleft palate examined. The phenomenon has not been reported before and does not appear to be a feature of the nasopharyngeal wall in noncleft individuals. PMID- 2253390 TI - Agnathia and associated malformations: a case report. AB - A case of a rare first branchial arch anomaly with severe hypoplasia of the mandible and fusion between the mandible and adjacent bones is presented. The patient also had intracranial, cardiac, and acral deformities. The craniofacial malformations may reflect incomplete separation of the first branchial arch into its maxillary and mandibular processes. The association between the craniofacial and other corporal anomalies is unknown. PMID- 2253391 TI - Observation: a comment on "A discussion of presurgical orthodontics in patients with clefts". PMID- 2253392 TI - Resorption of grafted alveolar bone associated with abnormal dental follicle: is it a rare incident or not? PMID- 2253393 TI - Redox electrode for monitoring dehydrogenase-catalyzed reactions. AB - Dehydrogenase-catalyzed reactions are widely used in the quantitative analysis of chemical substances. In these reactions the common product is NADH. By including diaphorase and a redox couple (ferricyanide and ferrocyanide ions) in the assay medium, the production of NADH becomes detectable with a redox electrode. The relationship between the redox potential and the substrate concentration can be simplified by reducing the number of variables. With the method described here the Nernst equation reduces to E = K - S log[con.], where E is the redox potential, K and S are the intercept and the slope of a straight line respectively, and [con.] is the sample concentration. The method was successfully applied to the analysis of blood alcohol, and shows promise for assaying many other tissue constituents. PMID- 2253394 TI - Myoadenylate deaminase deficiency studies on normal and deaminase-deficient skeletal muscle. AB - Two kinetically and regulatory similar isoforms of AMP-deaminase were demonstrated in adult human skeletal muscle. In an extract from normal muscle, 5 10% of the AMP-deaminase activity was released from a phosphocellulose column in the 0.75 mol/l potassium chloride eluate, the remaning activity being eluted with 2.0 mol/l potassium chloride. In a muscle extract from a patient with myoadenylate deaminase deficiency the total AMP-deaminase activity was only 2% of the control, and it eluted mainly in 0.75 mol/l KCl fraction. The AMP-deaminase variant, which eluted with 2.0 mol/l KCl from the deficient muscle extract displayed kinetic properties distinctly different from those of normal muscle and resembled in this respect the isoform from fetal tissue. The experiments presented suggest that disturbances in the mechanisms regulating an alternative splicing of the primary transcript of skeletal muscle AMP-deaminase gene might be the molecular basis of the defect. PMID- 2253395 TI - Elevation of blood lactate and pyruvate levels in acute intermittent porphyria--a reflection of haem deficiency? AB - Blood lactate concentrations after glucose loading were significantly higher in 6 patients with acute intermittent porphyria in clinical remission than in 6 control subjects and the percentage rise in glucose pyruvate and lactate concentrations were greater in the porphyric subjects than in the control group. It is postulated that the raised lactate levels in the porphyric patient group may reflect haem deficiency affecting the cytochromes of the terminal respiratory chain. PMID- 2253397 TI - Enzyme immunosorbant assay of oestradiol in unextracted plasma using penicillinase as label. AB - An enzyme-linked immunosorbant assay (ELISA) for measuring oestradiol directly in plasma without extraction utilizing antibodies raised against oestradiol-3-(O carboxymethyl) ether-bovine serum albumin conjugate, and oestradiol-6-(O carboxymethyl) oxime linked to penicillinase (EC 3.5.2.6) as a marker was developed. Polyvinyl 96-well microtitre plates were used for immobilization of anti-oestradiol IgG. Standards of oestradiol (92 to 9,190 pmol/l were prepared in oestradiol-free plasma and 8-anilino-1-naphthalene sulphonic acid (8-ANS, 5 mg/ml of 10 mmol/l PBS) was added to the microtitre plate wells to displace oestradiol from plasma binding proteins. The assay had a lower limit of detection of 92 pmol/l plasma and could be performed within 4 h. Comparison of oestradiol values of 51 plasma specimens obtained by ELISA with those of radioimmunoassay (RIA), in which oestradiol was extracted with diethyl ether, showed good correlation (y = 0.786x + 0.03; r = 0.900). PMID- 2253396 TI - Comparison of the effects of purified human alpha 1-antichymotrypsin and alpha 1 proteinase inhibitor on NK cytotoxicity: only alpha 1-proteinase inhibitor inhibits natural killing. AB - While an inhibitory effect on natural killer (NK) cell activity was demonstrated with partially purified alpha 1 Achy, neither highly purified alpha 1 Achy from two healthy donors nor from one patient with giant-cell arteritis, which carries more highly branched glycans, inhibited the NK cytotoxicity. Our purification procedure, based on immunoaffinity chromatography and gel filtration, was not in question since the pure alpha 1-proteinase inhibitor (alpha 1PI) prepared in our laboratory by using a similar procedure continued to inhibit the NK cytotoxicity. If an inhibitory effect not related to antiprotease activity occurs with alpha 1PI, it is surprising that it is not shared by alpha 1 Achy which, like alpha 1PI, belongs to the serpin family and which possesses a strong structural homology with alpha 1PI. Our finding that alpha 1PI is able to affect human NK cytotoxicity while alpha 1 Achy (even with more highly branched glycans) is unable to suggests that events controlling NK activity may involve other enzymes than chymotrypsin-like enzymes. PMID- 2253398 TI - Immunoreactive vasopressin in end stage renal failure. AB - Patients with end stage renal failure have been shown to have higher basal concentrations of plasma arginine vasopressin than subjects with normal renal function. Immunoreactive vasopressin was detected in plasma from patients with severe chronic renal failure and a healthy subject at an elution volume identical to that previously determined with synthetic vasopressin. Assay of all fractions yielded identical chromatograms in the renal failure and healthy control groups. We conclude that the plasma immunoreactive vasopressin in end stage renal failure plasma coelutes with synthetic vasopressin and that the elevated concentrations found in these patients are not due to non-specific depression of binding in the vasopressin radioimmunoassay by circulating substances in renal failure. PMID- 2253399 TI - Theoretical isoelectric points and electric charges of mutated human hemoglobin subunits. AB - Isoelectric point values have been determined from a theoretical standpoint for alpha, beta, gamma and delta human abnormal subunits bearing elimination or addition of 1-2 different aminoacids with acid-base residues. The charge distribution, in relation to pH values, of the four types of subunits are also reported. These values may be of interest both to predict the electrophoretic behaviour and to characterize human abnormal hemoglobins. PMID- 2253400 TI - A sensitive radioimmunoassay using a monoclonal antibody that is equipotent for ercalcitriol and calcitriol (1,25-dihydroxy vitamin D2 and D3). AB - A monoclonal antibody has been used in a sensitive radioimmunoassay that measures 1,25-dihydroxyvitamin D2 (ercalcitriol) and 1,25-dihydroxyvitamin D3 (calcitriol) with equal potency. This important characteristic has not been reported for any other radioimmunoassay for 1,25-dihydroxyvitamin D. The two forms can be assayed in human serum together or individually after HPLC separation. Sample preparation entails acetonitrile extraction followed by C18-Sep-pak chromatography and HPLC. The assay measures 98% of added analyte, and achieves inter- and intra-assay coefficients of variation of 10.7% at 34 pg/ml and 7.8% at 81 pg/ml respectively. The limit of detection is 1.25 pg/tube and 50% displacement of bound ligand is achieved at 14 pg/tube. The reference interval is 20-50 pg/ml, mean 35. The correlation between results from the monoclonal radioimmunoassay and an established polyclonal antibody method was r = 0.98, slope 0.99. The assay has particular application in patients treated with vitamin D2 since 1,25 dihydroxyvitamin D2 can now be measured accurately in the presence of 1,25 dihydroxyvitamin D3. PMID- 2253401 TI - The effect of oral contraceptive use and pregnancy on the daily rhythm of cortisol and cortisone. AB - The effect of oral contraceptives and of pregnancy on the daily rhythm of cortisol, and its metabolite cortisone in plasma and saliva has been investigated. In both conditions the total plasma cortisol levels were raised to the same extent, the mean values in saliva in the oral contraceptive users being intermediate between those in pregnancy and in the controls, particularly in the morning. Salivary cortisone levels were more related to salivary cortisol than to total plasma cortisone which exhibited a rather flat daily rhythm. There was a shift in peak values for salivary cortisol and cortisone towards late morning: this may be due to a delay in the daily activation of the hypothalamic-pituitary adrenal axis in these patients. PMID- 2253402 TI - Does Tamm-Horsfall mucoprotein inhibit or promote calcium oxalate crystallization in human urine? AB - Using two different experimental techniques, Tamm-Horsfall mucoprotein (THM) has been reported both to inhibit and to promote calcium oxalate (CaOx) crystallization in ultrafiltered human urine. In this study, these two techniques were used to compare the effects of THM on CaOx crystallization in the same ultrafiltered urine samples. Urine was collected from 10 healthy men and ultrafiltered (10,000 Da). Each sample was divided and to one half was added sufficient human THM to give a final concentration of 35 mg/L. CaOx crystallization was induced in the samples by addition of an oxalate load and by evaporation. Using the evaporation technique THM significantly increased the deposition of CaOx determined as 14C-oxalate, from 9,772 cpm to 43,652 cpm (P less than 0.01). Using the oxalate load method THM had no effect on the metastable limits of the urine with respect to CaOx, and significantly increased the volume of particulate material deposited from 26,000 to 39,995 microns 3/microliters - an increase of 54%. This increase was reduced to 21% when values were corrected for the volume of THM particles recorded in control samples to which no oxalate load was added. Using 14C-oxalate, it was shown that this increase in volume could not be attributed to an enhanced deposition of crystalline CaOx, but was probably the result of an increased polymerization of THM in the presence of CaOx crystals. Despite this, the average size of the particles precipitated in the presence of THM (6.5 microns) was significantly (P less than 0.01) less than that observed in the absence of THM (12.1 microns). It was concluded that the effect of THM on CaOx crystallization in urine depends upon the methodology used to assess it and that promotion would only be expected in vivo in cases of extreme dehydration. Under usual physiological conditions THM would be expected to inhibit CaOx crystal aggregation and to have little effect, if any, on the amount of crystalline material deposited. PMID- 2253403 TI - Urinary proteins and red blood cell membrane negative charges in diabetes mellitus. AB - The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2 microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2 microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy. PMID- 2253405 TI - Different molecular forms of acid-stable trypsin inhibitor in normal and uremic plasma. PMID- 2253404 TI - Immunological study on hypophosphatasia. PMID- 2253406 TI - Serum alkaline phosphatase in sickle cell anaemia. PMID- 2253407 TI - Serum soluble interleukin 2 receptor in hyperthyroid Graves' disease and effect of carbimazole therapy. AB - To study the activation of T lymphocytes in hyperthyroid Graves' disease, the serum concentrations of soluble interleukin 2 receptors (sIL2R) were determined during active thyrotoxicosis and following the return to a euthyroid state with carbimazole therapy. Serum sIL2R was measured by an enzyme linked immunoassay. The mean +/- SD serum sIL2R concentration during untreated hyperthyroidism was elevated as compared with controls (919.1 +/- 523.4 vs 374.2 +/- 189.4 U/ml, P less than 0.005). However, after carbimazole therapy the serum sIL2R in euthyroid patients fell to 377.9 +/- 90.3 U/ml, which did not differ from healthy controls. Serum sIL2R correlated significantly with the serum free T3 only during hyperthyroidism (r = 0.678, P less than 0.01). Our study suggests that in vivo measurement of serum sIL2R released from activated T lymphocytes is a useful immunological indicator of disease activity. PMID- 2253408 TI - Pharmacological 'rescue' of the corpus luteum results in increased inhibin production. AB - Inhibin production by the corpus luteum was investigated by undertaking pharmacological rescue of the corpus luteum with hCG in four healthy women. Blood samples were collected daily for two menstrual cycles. Starting 7 days after the LH surge in the second cycle, incremental doses of hCG (125-8000 IU) were administered daily for 7 days resulting in hCG levels comparable to those seen in normal pregnancy. Following hCG, the luteal phase was prolonged and there were significant increases in the plasma concentrations of inhibin (P less than 0.05), and oestradiol (P less than 0.05). The progesterone concentration was maintained at the mid-luteal phase peak and as a result was significantly higher than those on the equivalent days of the control cycle (P less than 0.05). It was concluded that rescue of the corpus luteum with physiological levels of hCG resulted in a significant output of inhibin, thus suggesting that the corpus luteum is a significant source of inhibin in early pregnancy. PMID- 2253409 TI - In-situ analysis of calcitonin and CGRP expression in medullary thyroid carcinoma. AB - A combination of immunocytochemistry (ICC) and in-situ hybridization (ISH) applied to formalin-fixed tissue sections was used to analyse the differential expression of calcitonin and CGRP genes, at both peptide and mRNA levels, in normal and neoplastic human thyroid C cells. Calcitonin peptide was readily detectable in normal C cells but its abundance in the neoplastic C cells of medullary thyroid carcinoma (MTC) was reduced in correlation with the degree of tumour differentiation. Conversely, the content of calcitonin mRNA was higher in MTC than in normal C cells and was not significantly related to tumour differentiation. Both the peptide and mRNA of CGRP were present at much lower levels than those of calcitonin in normal C cells but were increased in neoplastic C cells. We conclude that neoplasia of thyroid C cells is associated with (i) an increase in the content of CGRP mRNA and peptide relative to that of calcitonin, consistent with a defect in control of transcript processing, and (ii) a decrease in the ratio of calcitonin peptide to mRNA abundance relative to the normal, suggesting a defect in synthesis or storage of the peptide. ISH analysis of calcitonin mRNA may therefore be a very valuable addition to ICC analysis of the peptide as a diagnostic and prognostic marker for MTC. PMID- 2253410 TI - Screening for thyroid diseases. PMID- 2253411 TI - Ovarian electrocautery or hormone therapy in the treatment of polycystic ovary syndrome. PMID- 2253412 TI - Production of immunoreactive inhibin by a virilizing ovarian tumour (Sertoli Leydig tumour). AB - A 59-year-old post-menopausal woman was admitted to the hospital with atypical vaginal bleeding and hirsute lower extremities. There was a high serum testosterone level (15.8 nmol/l) and also an appreciable serum immunoreactive inhibin level. No adrenal or ovarian lesions were detected by conventional imaging procedures. Selective blood sampling was performed during venous catheterization and showed that testosterone and inhibin levels were highest in the right ovarian vein. Laparotomy revealed a Sertoli-Leydig tumour in the right ovary, which was excised. Post-operatively, immunoreactive inhibin became undetectable while the testosterone level fell to 2.8 nmol/l. Specific radioimmunoassay showed a high immunoreactive inhibin content in the tumour. These findings indicate that Sertoli-Leydig tumours can produce both testosterone and immunoreactive inhibin, both of which would then inhibit LH and FSH release to produce the symptoms seen in this patient. Thus, assay of inhibin may aid in the differential diagnosis of virilizing tumours. PMID- 2253413 TI - The effect of radioactive iodine treatment on thyroid C cells. AB - To determine the effect of radioiodine treatment on thyroid C cells, calcitonin (CT) levels were measured by RIA before and after intravenous calcium stimulation (2 mg/kg body-weight elemental calcium) in 22 women treated with 131I for hyperthyroidism. The results were compared with sex, age and weight-matched normal controls. There was a slight but statistically significant decrease in basal CT levels of the patients compared to the control group (mean +/- SE; 0.009 +/- 0.001 vs 0.011 +/- 0.001 pmol/l, P less than 0.05). The mean stimulated CT level of the patient group was significantly lower than that of the controls (0.010 +/- 0.001 vs. 0.018 +/- 0.003 pmol/l, P less than 0.001). The absence or presence of 131I-induced hypothyroidism at the time of the study did not influence basal or stimulated CT levels. Basal and stimulated CT levels were significantly lower in the patients with Graves' disease than in the patients with toxic nodular goitre. We conclude that 131I used to correct hyperthyroidism may cause marked CT deficiency. PMID- 2253414 TI - Twenty-four-hour profiles of growth hormone, prolactin and cortisol in the chronic vegetative state. AB - The 24-h profiles of growth hormone (GH), prolactin (PRL) and cortisol were obtained from 11 patients in the chronic vegetative state in order to gain more insight into the neuroendocrine alterations caused by widespread suprahypothalamic brain damage. Age and sex-matched normal subjects served as a control group. Patients had fewer high-amplitude GH peaks (greater than 20 mU/l: 6 peaks/24 h vs 21 peaks/24-h in controls) and a (non-significant) tendency towards higher basal GH concentrations. PRL concentrations were higher in patients (296 +/- 212 (SD) vs 120 +/- 28 mU/l). Cosinor analysis also showed that 24-h rhythmicity was preserved, but acrophases were more dispersed. A nocturnal PRL acrophase occurred in only three of 11 patients but in 10 of 11 control subjects. The number of PRL peaks was the same in patients and controls. Cortisol concentrations were also higher in patients (298.3 +/- 114.6 vs 193.6 +/- 97.4 nmol/l) with a preserved circadian rhythm. The acrophases, however, were likewise more dispersed. There was no difference in the number of cortisol peaks between patients and controls, but the mean peak duration was shorter in patients (75.4 +/- 28.1 vs 109.5 +/- 28.2 min). The stage of remission was negatively correlated with the 24-h mean and the mean peak amplitude of PRL. No patient showed a normal organization of sleep stages. On visual analysis there was no apparent association between EEG patterns and hormonal parameters. These results suggest that the endocrine hypothalamus is essentially intact in the chronic vegetative state. The observed changes may be due to an altered input from extrahypothalamic brain structures. PMID- 2253415 TI - Osteoporosis. PMID- 2253416 TI - [Computed tomographic analyses on skeletal muscles in bulbar spinal muscular atrophy]. AB - We analysed the patterns of skeletal muscular involvement in 18 patients with bulbar-spinal muscular atrophy (BSMA) of the Kennedy-Alter-Sung type by using the computed tomographic scanner. Fatty infiltrations were prominent in various skeletal muscles of extremities and trunk, and its degree was severe in the following numerical orders; the gluteal muscles, flexors of the thighs, flexors of the lower extremities, extensors and the adductors of the thighs, the paraspinal muscles, and extensors of the lower extremities. There was statistically significant correlation between fatty infiltrations in flexors of the lower extremities and duration of illness. And were noted findings that the skeletal muscle lesion progressed with the preserved fasciae and sectional areas, fatty infiltrations in the lower extremities were more conspicuous in flexors than in extensors, and compensatory hypertrophic muscles in the thigh were apparent in 50% of cases. In conclusions, the computed tomographic analyses on skeletal muscle of BSMA may be useful to detect distributions, progression of the muscle lesion, in addition to a profile of the myopathic alterations of the disease. PMID- 2253417 TI - [Clinical significance of serum cardiac myosin light chain I in patients with muscular dystrophy]. AB - We examined serum cardiac myosin light chain I (LCI), serum creatine kinase (CK) levels and left ventricular function in patients with muscular dystrophy and secondary cardiac involvement. LCI levels were determined by a two-site immunoradiometric assay method in 25 patients with muscular dystrophy and 10 normal subjects. This study included 15 patients with Duchenne muscular dystrophy (DMD), 8 patients with Fukuyama type congenital muscular dystrophy (FCMD) and 2 sisters with non-Fukuyama type congenital muscular dystrophy (nFCMD). We measured the value of left ventricular fractional shortening (FS) using echocardiography. All patients with DMD and FCMD showed moderate or severe skeletal muscle weakness. The mean values of LCI were significantly higher in patients with DMD (11.0 +/- 8.3 ng/ml, p less than 0.01) and in patients with FCMD (1.6 +/- 1.4 ng/ml, p less than 0.05) than in normal subjects (0.3 +/- 0.2 ng/ml). In patients with DMD, LCI level correlated closely with CK level (r = 0.81, p less than 0.01) but not with FS (r = 0.35, n.s.). In patients with FCMD, LCI level correlated significantly with CK level (r = 0.75, p less than 0.05) but not with FS (r = 0.44, n.s.). Close correlation between LCI and CK levels was thought to result from the cross reaction between cardiac LCI and myosin light chains of skeletal muscle in the assay method we used. Two siblings with nFCMD showed mild skeletal muscle weakness. A 22-year-old sister with mild left ventricular dysfunction (FS = 0.41) showed high level of CK (4794/U/L) and mild elevation of LCI (7.3 ngml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253418 TI - [Herpes simplex brainstem encephalitis presenting high intensity area on MRI--a case report]. AB - A case of herpes simplex encephalitis with high signal intensity area in brainstem on MRI was presented. A 44 year-old woman suffered from oral aphthous ulcerations in the end of 1988, and then it improved naturally. Oral aphtha appeared again on February 1988 followed by resistant fever to antibiotics and right hemiparesis. She was admitted to our hospital on 25 February 1988. Neurological examination revealed mild consciousness disturbance, neck stiffness, right-side deviation of tongue with dysarthria and right hemiparesis with bilateral plantar extensor reflex. Right hemisensory deficit in all modalities and truncal ataxia was also detected. Some aphthous ulcerations were revealed in oral cavity, but there were no ulcers on genitalia nor uveitis. CSF showed 32 mononuclear cells/mm3, protein 52 mg/dl and glucose 97 mg/dl. CSF culture and india ink stain, and serum autoantibodies were all negative. EEG and CT scan with contrast enhancement showed no significant abnormalities. T2-weighted brain MRI revealed high intensity area in the center of the pons. Anti-herpes simplex virus (HSV) type I antibody titer (FA method) in both serum and CSF were highly positive. Neurological symptoms gradually improved on the therapy of aciclovir and adrenal cortico-steroid. High intensity area in the pons on MRI was also gradually reduced. In this case, complete diagnostic differentiation from neuro Behcet disease was difficult, but this case did not meet its diagnostic criteria. From the change of anti-HSV antibody titer both in serum and CSF, we diagnosed this case HSV brainstem encephalitis presenting high intensity area in the pons on MRI which has never been reported. PMID- 2253419 TI - [Myasthenia gravis associated with tonic pupil]. AB - A 41 year-old female patient with acquired autoimmune myasthenia gravis (MG, IIa type) and tonic pupil (Adie's pupil) of the right side was reported. Adie's pupil was pointed out at the same time of the clinical diagnosis of MG in September, 1988. She had the solitary thymoma identified by pneumo-mediastinograph and mediastinal CT scan. Results of the positive anti-nicotinic AChR antibody titer, the positive edrophonium test and the electrophysiological examination gave unambiguous evidences of acquired autoimmune MG with thymoma. Instillations to the eyes of cocaine, pilocarpine and epinephrine, and the pupillary response to the intravenous injection of edrophonium revealed the postganglionic abnormality mainly in the parasympathetic system. There were no other overt symptoms due to dysautonomia. She refused thymectomy. Her myasthenic and pupillary signs became gradually improving without any immunosuppressive medications. It is concluded that two diseases of the patient may be probably caused by multiple organ- or tissue-specific autoantibodies, in addition to pathogenetic significance of Adie's pupil. PMID- 2253420 TI - [An autopsy case of primary cerebral malignant lymphoma initiated with choreoathetosis]. AB - An autopsy case of primary cerebral malignant lymphoma with choreoathetosis as initial and main symptom was reported. A 57-year-old woman showed choreoathetosis in right upper and lower extremities, and mental aberration. Cranial CT scan showed high density areas in bilateral frontal lobes, right caudate nucleus and putamen, right vermis of cerebellum, left corpus callosum, all of which revealed increased high density by enhancement. The diagnosis of malignant lymphoma was confirmed by the findings of CT scan-guided stereotaxic biopsy. Although the consciousness became gradually drowsy, neurological signs and symptoms and cranial CT scan's findings were improved by radiation therapy. Subsequently, she developed paresis of left upper and bilateral lower extremities and died of sepsis and disseminated intravascular coagulation 8 months after the onset. Neuropathological examination revealed macroscopically atrophy and brawnish discoloration in bilateral caudate nuclei and right globus pallidus. Microscopically, there were invasions of tumor cells in the subependymal perivascular space of ventricles and subarachnoidal spaces of cerebellum and brainstem. The bilateral heads of caudate nuclei revealed severe atrophy, neuronal loss and astrocytic proliferation induced by tumor cell invasion into the head of caudate nuclei, of which body and tail were well preserved. The globus pallidus and putamen did not show any abnormalities on left side, but the right globus pallidus was atrophic, and middle part of putamen and globus pallidus showed tissue rarefaction, loss of myelin, and astrocytic proliferation. However, neuronal cells were relatively preserved. In the spinal cord, the tumor cells invaded to the subarachnoidal and perivascular spaces and necrosis of spinal parenchyma were noted from lower cervical to upper thoracic cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253421 TI - [Two cases of X-linked ichthyosis associated with myopathies]. AB - X-linked ichthyosis is an inborn error of metabolism due to the deficiency of steroid sulfatase. We reported two cases of the patients associated with myopathies, which are Duchenne muscular dystrophy (DMD) and myotonic dystrophy (MyD), respectively. In addition to DMD and MyD, they showed corneal opacities, lack of steroid-sulfatase activities in peripheral leukocytes and massive accumulation of cholesterol sulfate in plasma. Such cases were not reported, previously. Assay of steroid sulfatase and cholesterol sulfate in the patients having ichthyosis is important to elucidate the wide clinical spectrum of steroid sulfatase deficiency. PMID- 2253422 TI - [Thrombosis of the superior cerebral vein with hemorrhagic cerebral infarction- serial MRI and pathological study of a case]. AB - We reported an autopsy case of thrombotic occlusion of the superior cerebral vein with hemorrhagic laminar necrosis of the right parietal cortex. A 68-year-old woman was admitted to our hospital because of a severe headache and left hemiplegia of acute onset. There was a past history of hypertension, fever of unknown origin, leukocytopenia and nasal dermatitis. Magnetic resonance images (MRI) disclosed thrombosis of the superior sagittal sinus and of the right parietal cortical vein as well as right parieto-occipital cerebral infarction. Although she improved with mild sequelae, the subsequent MRI showed a recurrent thrombosis of the superior sagittal sinus. Ten months after the onset she died suddenly, presumably due to acute myocardial infarction. Pathologically, thrombotic occlusion of the right parietal cortical vein, recurrent thrombosis of the superior sagittal sinus and old hemorrhagic cortical laminar necrosis of the right parietal region were revealed. Moreover, intracranial arteritis and phlebitis were observed, as well as arteriolitis in the peripheral nerves. In our case, MRI was useful for the diagnosis and following the course of cerebral venous thrombosis. Cerebral noninfective vasculitis may well have caused the venous thrombosis. PMID- 2253423 TI - [Intradural extramedullary tumor of lower spinal cord in a 89-year-old man with cervical spondylosis and lumbar spondylolisthesis]. AB - A 89-year-old man was admitted because of slowly progressive gait disturbance during these several years. Neurological examination revealed paraparesis with bilateral sensory disturbance in the lower extremities, more severely on the left side. Vibration sense was almost completely disturbed under the level of bilateral crista iliaca. Deep tendon reflexes decreased in the lower extremities. No urinary incontinence was observed. The narrow spinal canal and cervical spondylosis were seen at the C 5-6 level, showing the anterior-posterior distance of 10 mm. Computed tomography of the lumbar spine showed spondylolisthesis between the level 4 and 5. CSF showed high protein concentration (300 mg/dl), whereas normal cell counts. These findings suggested the following two possibilities; cervical myelopathy associated with the disturbance of the cauda equina due to lumbar spondylolisthesis, or the disturbance at the lower thoracic or upper lumbar level of spinal cord. The spinal MRI revealed the irregular mass lesion in the lower spinal cord at the level of spine Th 11-12 on T2 weighted images, with enhancement by Gd-DTPA on T1 weighted images. These MRI findings suggested the intradural extramedullary tumor, such as benign neurinoma or meningioma. No clear cut lesions were found at the cervical spinal cord or at the cauda equina. MRI was useful for the diagnosis of sites and lesions of spinal cord in the present case, whose neurological signs and symptoms could be explained by the coexistent cervical spondylosis and lumbar spondylolisthesis. PMID- 2253424 TI - [A case of long thoracic nerve palsy, with winged scapula, as a result of prolonged exertion on practicing archery]. AB - Reports of isolated long thoracic nerve palsy are rare in Japan. We reported a case of isolated long thoracic nerve palsy, resulted from recurrent injury to the nerve. Muscle CT and electrodiagnostic study were useful for confirming diagnosis of this cases. This patient was a student aged 20 years, with nothing of importance in his family or past history. After he started practicing archery, winging of left scapula was gradually developed. Physical examination revealed weakness and atrophy of left serratus anterior muscle. There was no wasting and weakness of other should girdle muscles. Hematochemical tests were normal, except slight hyperthyroidism. Radiography and myelography of the cervical spine were normal. Muscle CT of upper thoracic level demonstrated atrophy of left serratus anterior muscle, and no abnormality were found in other muscles. Electromyogram of the left serratus anterior revealed discrete activity of reduced amplitude, and fibrillation potentials and positive sharp waves. Conduction time for left long thoracic nerve was prolonged, and amplitude of the evoked response was small and there were temporal dispersion. Muscle CT and electrodiagnostic studies were suggestive of neuroapraxia of left long thoracic nerve. Over stretching or compression during exercises may be responsible for the damage to the long thoracic nerve. PMID- 2253425 TI - [Improvement in hemiballism after transient hypoxia in a case of subthalamic hemorrhage]. AB - A 73-year-old man was admitted complaining of violent involuntary movement in the left upper and lower extremities. He had a ten-year history of hypertension and had had a left thalamic hemorrhage 6 years before admission. On neurological examination Horner's sign in the right eye, typical hemiballism in the left extremities and right hemiparesis, which was caused by the previous left thalamic hemorrhage, were observed. CT scan and MRI revealed recent hemorrhage in the right subthalamic nucleus. Haloperidol, tiapride and diazepam were administered to ameliorate the ballism, but they had to be reduced in amount because of the development of parkinsonism. Two months after onset, when there was still moderate ballism, he suffocated due to a swallowing disturbance. After two hours' coma, consciousness returned gradually. Twenty-four hours after suffocation, the neurological examination revealed normal consciousness and no deterioration in other neurological symptoms, but the ballism had almost disappeared without medication. No change was detected in MRI findings and the blood flows in the basal ganglia before and after suffocation. It is interesting that transient hypoxia due to suffocation reduced hemiballism in this patient without neuroradiological findings of ischemia in the basal ganglia. The mechanisms of reduction of hemiballism after transient hypoxia were discussed. PMID- 2253426 TI - [A case of pure trigeminal motor neuropathy]. AB - We reported a case of pure trigeminal motor neuropathy. A 57-year-old man was admitted with the complaints of vague headache and left upper limb numbness. Neurological examination showed mild wasting of the right masseter muscle on chewing. The jaw deviated to the right when he opened his mouth fully. Corneal reflex was intact bilaterally and so was the sensation on the face and taste. Mild hemiparesis including the face was observed on the left. Laboratory data including cerebrospinal fluid analysis were normal except for mild glucose intolerance. Blink reflex, brainstem auditory response and trigeminal sensory evoked potential elicited by electric stimulation of the lower lip were all normal. EMG findings obtained from the left masseter and lateral pterygoid muscles were neurogenic. The CT scan demonstrated a characteristically distributed low density area, which substituted the muscle supplied by the motor branch of he trigeminal nerve, namely, the right masseter, temporalis, lateral and medial pterygoid muscles. With MRI, the lesion was high on T1 and T2 weighted images. In addition, spotty high signal intensities suggestive of small infarction were observed in the bilateral centrum semiovale on T2 weighted images. Judging from the above results, the present case was believed to have pure motor trigeminal neuropathy confirmed by electrophysiological findings and image analyses together with clinical features. The mild left hemiparesis was thought to be incidental complication of vascular origin. PMID- 2253427 TI - [The quantitative analysis of electroencephalography in primary hypothyroidism]. AB - The EEG topography was recorded in the patients with primary hypothyroidism, and the relationship between equivalent potential and blood thyroid hormonal levels were investigated. To determine the relationship between the % equivalent potential fraction (%EPF) and the levels of blood free T3, free T4, and TSH in each patient, regression lines were drawn in respective EEG spectral bands. The %EPF of each patient showed a tendency to have a negative correlation with the values of blood free T3 and free T4 in slow frequency spectral bands such as delta, theta, and alpha 1 waves, whereas a positive correlation in fast frequency bands such as alpha 2, beta 1, and beta 2 waves. In particular %EPF had a significant relationship with blood free T3 levels in alpha 1 and beta 2 spectral bands. These results suggest that the thyroid hormones may have influence on the mechanisms of EEG rhythm formation in primary pypothyroidism. PMID- 2253428 TI - [A case of posterior cerebral artery territory infarction with micropsia as the chief complaint]. AB - A 63-year-old man was admitted to the hospital complaining that all objects in his vision suddenly appeared small. Examination on admission revealed amnesia of recent events, recognition memory deficits, emotional disturbance, right upper quadrantanopsia and micropsia. The patient was diagnosed as posterior cerebral artery territory infarction based on brain CT scan and MRI findings which showed an ischemic lesion involving the left occipital lobe and hippocampus. We regarded the quadrantanopsia to have originated in the occipital lobe lesion and memory and emotional disturbances to have originated in the hippocampal lesion. After admission, micropsia and disturbances of memory and emotion improved within a month, but the quadrantanopsia did not recover. A comparison of the 25th and 2nd day brain CT scans indicated that the low density of the ischemic lesion near the hippocampus had become less clear and smaller. These findings suggest that the pathogenesis of micropsia in this case was a visual perceptional abnormality due to edematous change in the structures near the hippocampus. Cases of occipital artery territory infarction with micropsia, disturbances of memory and emotion, and quadrantanopsia appear to be rare, but micropsia may be overlooked since it is often masked by disturbance of memory or emotion. PMID- 2253429 TI - [Lacune in the white matter revealed by MRI in a case of pure motor monoparesis]. AB - It has been reported that most of pure motor monoparesis were induced by the superficial mass lesions in the cerebral hemisphere. However, pure motor monoparesis due to lacune is rare. We reported a 81 year-old woman of pure motor monoparesis caused by the lacunar infarction in the parasagittal subcortical white matter. That lesion could not be detected by CT scan performed at onset, and 18 days later after the stroke, but was detected by MRI performed 5 days after the onset. The coronal section of MRI showed the stick-like shaped small infarction in the white matter, which runs along the corticospinal tract, just under the precentral gyrus. The coronal section of MRI is useful for the demonstration of the anatomical localization of lacune. PMID- 2253430 TI - The Indian experience with hypertrophic pyloric stenosis. AB - A study of 58 consecutive Indian infants operated for congenital hypertrophic pyloric stenosis revealed an accentuated male predominance in the incidence of the disease and far less preoperative hemetemesis as compared to that in their Western counterparts. 'Pyloric tumor' was palpable in 89% of cases. Only 34.5% of these infants were first born. Postoperative vomiting occurred in 13.8% of patients and wound sepsis was not encountered. Air contrast radiography confirmed the diagnosis in clinically doubtful cases. PMID- 2253431 TI - Serum carotene concentrations in normal infants and children. AB - The blood of 444 healthy Canadian children (246 males and 198 females) aged 6 days to 18 years was analyzed to determine the concentration of serum carotene. The serum carotene concentration was very low in the first six months of life. In the first three months of life, breast fed infants had significantly higher serum carotene concentration than infants who were formula fed. Infants 7 to 12 months of age had the highest serum carotene concentration. The serum carotene concentration dropped off after the age of one year and remained low until two years of age. After two years of age, the serum carotene concentration showed a progressive and small rise until the age of six to seven years and then fell until the age of 14 to 18 years. The serum carotene concentration did not appear to vary according to the sex of the child except for infants 7 to 12 months of age. In infants 7 to 12 months of age, girls had a higher serum carotene concentration. The measurement of the serum carotene concentration is a simple screening test for fat malabsorption. Our study provides the normal range of serum carotene concentration for children of various age groups. PMID- 2253432 TI - Croup in older children. Case report of 2 school-age children with croup. PMID- 2253433 TI - Munchausen syndrome by proxy presenting as factitious apnea. PMID- 2253434 TI - Omental cystic lymphohemangioma in children. Acute presentation. PMID- 2253435 TI - Acute encephalopathy from shigellosis with localized brain edema. PMID- 2253436 TI - Mycoplasma pneumoniae infections associated with severe mucositis. PMID- 2253437 TI - Poland's syndrome. PMID- 2253439 TI - Proteus mirabilis isolation as a sign of nasal foreign body. PMID- 2253438 TI - 'Abandoned' parents--a challenge for health professionals. PMID- 2253440 TI - Pediatric chest pain: a prospective study. PMID- 2253441 TI - Lead. AB - This article reviews historical and current uses of lead and sources of absorbed lead, such as water, lead-based paint, cookware, and bullet wounds. The means of absorption, collection of specimens, quantification methods, and effects of lead toxicity are discussed. PMID- 2253442 TI - Clinical toxicology II. Strategies for clinical laboratory management: horizontal and vertical integration in hospital laboratories. PMID- 2253443 TI - An update on arsenic. AB - Arsenic poisoning is more than just a medical curiosity. Cases of acute and chronic intoxication continue to occur in the United States. Much is now known about the biochemical mechanisms of injury, which has led to a rational basis for therapy. Most importantly, however, the clinician must stay alert to correctly diagnose and treat cases of arsenic poisoning. PMID- 2253444 TI - Human growth hormone. Its use and abuse. AB - The use of hGH may become a significant challenge to the sports world. Scientific and ethical questions regarding its use may become more pressing if synthetic hGH becomes available to the public. The potential appeal of hGH to athletic competitors is obvious, but at present no benefits of this hormone as an ergogenic aid have been clearly demonstrated. Indeed, clinical experience with acromegalics suggests that prolonged exposure to elevated doses of hGH produces detrimental neuromuscular responses. Perhaps an even more intense ethical issue concerns the use of hGH in children and adolescents. The use of hGH to increase height and thereby increase chances for athletic success may be tempting to both coaches and parents. Athletes, parents, coaches, and team physicians must be aware that hGH has not been shown to enhance athletic performance and that its potential long-term side effects are irreversible and even may be life threatening. PMID- 2253445 TI - Understanding digoxin use in the elderly patient. AB - There are many disease states in the elderly that mandate the use of drugs with extremely narrow therapeutic indexes and potentially fatal toxicity. Digoxin is one example of such drugs. It is extensively used for the treatment of congestive heart failure of diverse origin and of cardiac arrhythmias of supraventricular origin. Aging can produce changes in essentially all organ systems, which as a whole render geriatric patients particularly vulnerable to the toxic effects of digoxin. Among all age-related pharmacokinetic and pharmacodynamic changes, declining renal function is perhaps the most important factor that must be considered. This often means a significantly less efficient renal digoxin clearance, which necessitates a reduction in dosage. The geriatric population tends to consume more drugs and are more at risk for undesirable multidrug interactions than their younger counterparts. To name a few, quinidine, verapamil, amiodarone, and non-K(+)-sparing diuretics are notorious for predisposing the patient to digoxin toxicity when administered concurrently with digoxin. Therefore, digoxin must be prescribed to elderly patients with great judiciousness, with careful interpretation of serum digoxin assay, and due consideration of its intrinsic limitations. PMID- 2253446 TI - Drugs-of-abuse testing. Screening and confirmation. AB - It is essential to understand that any rapid urine drugs-of-abuse screening test should be confirmed by an equally sensitive and more specific test. In this regard, the confirmation procedure chosen should provide the most accurate and unequivocal results possible. Confirmation techniques other than GC/MS may be adequate for certain drugs of abuse, but GC/MS is generally accepted as the most rigorous confirmation technique for most drugs of abuse. It provides the best confirmatory information when performed appropriately. Consumers should be aware of the limitations of screening tests and the need for more specific confirmatory testing. Each drug-of-abuse testing claim must be supported by appropriate data. Labeling instructions and other pertinent information must be accurate. Labeling for drug-testing devices must provide adequate information about the intended use and expected performance, in addition to instructions for use, known limitations, and indications of the quality of performance. PMID- 2253447 TI - Quality assurance in drug testing laboratories. AB - Drug testing is currently regulated for Department of Defense and other federal agency programs and many of the QA actions listed in this article are mandated in the regulations cited. This trend will probably continue in an effort to ensure high-quality test results and may expand into private sector testing. Also, more drugs may be added to the list of the five currently mandated for federal agencies. It remains to be seen if the certified DTLs avoid the pitfalls of past programs. A good QA program will undoubtedly be the key to success. PMID- 2253448 TI - Mandatory drug testing in the United States. Opportunities and challenges for the medical review officer. AB - The authors discuss the challenging problems involved in designing a fair and accurate drug testing program. The role of the medical review officer is described in detail, including verification procedures, record keeping, and legal liability. PMID- 2253449 TI - The importance of calcium regulation in toxic cell injury. Studies utilizing the technology of digital imaging fluorescence microscopy. AB - The regulation of ions within the cell is of critical importance in both acute and chronic toxicology. Recently, new methods have been developed for measuring such changes in living cells and correlating them with studies of structure, function, and biochemistry. A major revolution has occurred from the linkage between the computer and the light microscope, which has resulted in the use of digital imaging fluorescence microscopy and video intensification microscopy coupled with image analysis. These methods have already yielded much additional information and it is anticipated that their further application by pathologists and toxicologists will continue to uncover the important role of ion deregulation and toxic cell injury. PMID- 2253450 TI - Toxicology and biocompatibility considerations in the evaluation of polymeric materials for biomedical applications. AB - It is necessary to determine the safety of polymeric materials through laboratory and animal testing before biomedical use can become more widespread. This article describes many of the methods used in analyzing the toxicology and biocompatibility of potentially important biomedical polymers. The study method used in the development of an important new class of polymeric materials for human use, the poly(anhydrides), is presented from laboratory bench to human clinical trials. PMID- 2253451 TI - Postmortem forensic toxicology. AB - After all of the analytic data have been accumulated, the final step in the toxicologic process is to assess the meaning of the results. In suspected drug intoxications, one must determine if the amount of toxicant or toxicants present in the appropriate specimens is consistent with producing lethality. This decision ultimately must be made by the medical examiner or coroner, who must also consider the history, scene investigation, and gross and microscopic autopsy findings in reaching this decision. Once the cause of death has been determined, the manner of death needs to be decided. This can produce another group of questions to be addressed by the toxicologist. Items such as route of administration, acute versus chronic dose, and consistency between drug concentrations and behavioral effects may be critical factors in assessing the manner of death. These questions may arise even if the cause of death is ruled not to be drug related. PMID- 2253452 TI - Cost analysis in the toxicology laboratory. AB - The process of determining laboratory sectional and departmental costs and test costs for instrument-generated and manually generated reportable results for toxicology laboratories has been outlined in this article. It is hoped that the basic principles outlined in the preceding text will clarify and elucidate one of the most important areas needed for laboratory fiscal integrity and its survival in these difficult times for health care providers. The following general principles derived from this article are helpful aids for managers of toxicology laboratories. 1. To manage a cost-effective, efficient toxicology laboratory, several factors must be considered: the laboratory's instrument configuration, test turnaround time needs, the test menu offered, the analytic methods used, the cost of labor based on time expended and the experience and educational level of the staff, and logistics that determine specimen delivery time and costs. 2. There is a wide variation in costs for toxicologic methods, which requires that an analysis of capital (equipment) purchase and operational (test performance) costs be performed to avoid waste, purchase wisely, and determine which tests consume the majority of the laboratory's resources. 3. Toxicologic analysis is composed of many complex steps. Each step must be individually cost-accounted. Screening test results must be confirmed, and the cost for both steps must be included in the cost per reportable result. 4. Total costs will vary in the same laboratory and between laboratories based on differences in salaries paid to technical staff, differences in reagent/supply costs, the number of technical staff needed to operate the analyzer or perform the method, and the inefficient use of highly paid staff to operate the analyzer or perform the method. 5. Since direct test costs vary directly with the type and number of analyzers or methods and are dependent on the operational mode designed by the manufacturer, laboratory managers should construct an actual test-cost data base for instrument or method in use to accurately compare costs using the "bottom-up" approach. 6. Laboratory expenses can be examined from three perspectives: total laboratory, laboratory section, and subsection workstation. The objective is to track all laboratory expenses through each of these levels. 7. In the final analysis, a portion of total laboratory expenses must be allocated to each unit of laboratory output--the billable procedure or, in laboratories where tests are not billed, the tests produced.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2253453 TI - Horizontal and vertical integration in hospital laboratories and the laboratory information system. AB - An understanding of horizontal and vertical integration and their quasi integration variants is important for pathologists to formulate a competitive strategy for hospital clinical laboratories. These basic organizational concepts, in turn, are based on the need to establish control over critical laboratory inputs and outputs. The pathologist seeks greater control of mission-critical system inputs and outputs to increase the quality and efficiency of the laboratory operations. The LIS produces horizontal integration of the various hospital laboratories by integrating them vertically. Forward vertical quasi integration of the laboratories is mediated primarily by the LIS through front end valued-added features such as reporting of results and creating a long-term on-line test result archive. These features increase the value of the information product of pathology for clinicians and increase the cost of switching to another system. The LIS can also serve as a means for customizing the information product of the laboratories to appeal to new market segments such as hospital administrators. PMID- 2253454 TI - Haptic classification of common objects: knowledge-driven exploration. AB - In Experiment 1, haptically available object properties that would be diagnostic for constrained common object classification at the basic and subordinate levels were elicited in a questionnaire. The results are considered in terms of the nature of the haptically derived representations of common objects. Initial data are also presented regarding knowledge of the natural co-occurrence of properties in haptic object perception. In Experiment 2, the hand movements executed during haptic classification of manipulable common objects were examined. Manual exploration consisted of a two-stage sequence, an initial generalized "grasp-and lift" routine, followed by a series of more specialized hand-movement patterns strongly driven by knowledge of the property diagnosticity for the specific object (obtained in Experiment 1). The current results may guide computational models of human haptic object classification and the development of perceptual systems for robots equipped with sensate dextrous hands, capable of intelligent exploration, recognition, and manipulation of concrete objects. PMID- 2253455 TI - Orthographic processing in visual word identification. AB - A series of experiments is reported examining orthographic priming effects between briefly presented pairs of letter strings. The experiments investigate the effects of the number and position of letters shared by primes and targets, and the effects of prime-target length. Priming effects increase nonlinearly as a function of both the number and the position of shared letters, and they are dependent on the positions of letters relative to both the end positions in the string and to the identities of their nearest neighbours. There is little effect of absolute string length on priming. These priming effects can be distinguished from intrusion errors where letters from primes are reported in response to targets. An account of orthographic processing is outlined which attributes priming to cooperative interactions between coarse relative-position coded letter cluster representations activated by primes and targets. The implications of the findings for understanding other effects in word recognition and reading are discussed. PMID- 2253456 TI - The public health implications of technology and its assessment. PMID- 2253457 TI - The impact of health technology assessment. PMID- 2253458 TI - Methodology used to monitor and evaluate in vitro fertilization and related procedures in Western Australia, 1983-1987. AB - A methodology was developed to support a comprehensive health services research project undertaken to monitor and evaluate the practice of in vitro fertilization (IVF) and related procedures, such as GIFT, in Western Australia (WA) from 1983 to 1987. The project included demographic, clinical and economic assessments of the new technology. The study subjects were the 1,240 couples who began IVF treatment between January 1, 1983 and December 30, 1986. Information was collected on all 2,982 treatment cycles commenced by June 30, 1987, and on the 273 births that resulted from these treatment cycles. Where relevant, comparisons were based on information obtained from the Australian Bureau of Statistics (ABS) census, the WA Midwives' Notification System and the WA Hospital Morbidity Data System. The need for long-term follow-up studies of children and participants is identified, as is the need for randomized clinical trials to evaluate more fully the success of the procedures where bilateral tubal blockage is not the indication for the treatment. PMID- 2253459 TI - Evaluating in vitro fertilization technology in Australia. AB - Following a summary background to the research, development and diffusion of in vitro fertilization (IVF) and related technologies in Australia from 1971 to 1989, two arguments are developed. The first is that what evaluations have so far been done of the safety, efficacy and effectiveness of the techniques used in this country have revealed worrying results. The second suggests that the existing methodologies of technology assessment and ethical control of human experimentation are themselves too limited to meet the recent goal, adopted by the 1988 Australian Health Ministers' Conference, of reducing inequities in health. The discussion offers suggestions for a more comprehensive methodology for the technical, ethical and social evaluation of these (and other) medical and health technologies, derived from recent social science research. PMID- 2253460 TI - Pap smear usage in New South Wales--impact of active promotion. AB - Less than 25 per cent of eligible Australian women have cervical ('Pap') smear tests in any year. Rates are particularly low (less than 8%) for women over 55 years, the group at highest risk of cervical cancer. A regional program, actively promoting Pap smears by widespread direct community intervention and attention to service needs, targeting women over 55 years and under 25 years, was conducted on the North Coast (population 132,000 women) immediately after a New South Wales State-wide media campaign in February 1988. The number of Pap smears done in the region increased 119 per cent for women over 55 years and 44 per cent for 15-24 year-olds during the promotion (63% overall) compared to New South Wales increases of 58 per cent for women over 55 years and 23 per cent for 15-24 year olds (31% overall). Differences between the North Coast and New South Wales were statistically significant for all age groups in March and in April for women over 55 years. Differences between New South Wales and Australia (no active promotion) were significant for women over 55 years in March and April. Records from a sample of 152 women attending clinics during the campaign showed 63 per cent had not had a smear test for three or more years, 10 per cent never.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253461 TI - An evaluation of a campaign to increase cervical cancer screening in rural Victoria. AB - This paper reports on the second of four regionally-based campaigns co-ordinated in rural Victoria by the Anti-Cancer Council of Victoria. The campaign encompassed community-based activities, general practitioner involvement and screening clinics. The impact of the campaign on Pap test rates and on the profile of women whose tests were reported by the Victorian Cytology Gynaecological Service is examined. We conclude that the campaign was successful in achieving its primary objective of attracting older and relatively underscreened women into having a Pap test. The special screening clinics were considered particularly effective in reaching women in the target audience. As a result of this campaign, new initiatives, were incorporated into subsequent programs. PMID- 2253462 TI - Pesticides in breast milk--a public health perspective. AB - Concern in the community about the risk of environmental hazards such as pesticides seems widespread. Pesticides have been widely used in agriculture to enhance food production and pesticide residues are now found in most human breast milk samples taken in industrialised countries. A breast milk survey on 158 women in Victoria was carried out during 1985/86 among women attending infant welfare centres. The survey showed that the mean sigma DDT and HCB concentrations had fallen by 62 per cent and 74 per cent respectively since the previous Victorian study in 1978. However dieldrin levels had not decreased significantly and most pesticide levels, as well as those for PCB, were above the acceptable daily intake levels set by the World Health Organization. The significance of these findings is still unclear. The response of governments and the media to this type of controversy is discussed in the light of the Victorian Breast Milk Survey. PMID- 2253463 TI - Validation studies from the Western Australian Congenital Malformations Registry. AB - A series of studies was undertaken in 1989 to validate the data held by the Western Australian Congenital Malformations Registry. Comparison with hospital discharge data identified 1585 children six years of age or younger with malformations discharged from hospitals in Western Australia in 1986, 226 of whom were not already recorded on the Congenital Malformations Register. When the records of a special register for cleft lip and palate were examined, all cases of facial cleft known to the special register were also recorded on the Malformations Register. Comparison of the Western Australian data for major groups of malformations with data from the South Australian Birth Defects Register raised the possibility of under ascertainment in Western Australia of cases of congenital heart disease. Multiple sources of ascertainment and evaluation of the ways in which such sources are tapped are important factors in striving for complete and accurate information on congenital malformations for research and public health purposes. PMID- 2253464 TI - Serious occupational injuries in Australia: some deficiencies of the existing data collections. AB - This study examines the incidence in Australia of "serious" occupational injuries, arbitrarily defined as those which resulted in absence from work for six months or more. The raw data were contained in computer print-outs specially prepared by the State offices of the Australian Bureau of Statistics (ABS) and the study includes analyses by age, sex, occupation and industry of the injured person. The unexpectedly large total of 14,281 high-severity injuries cannot be supported with confidence since the principal finding was the large and consistent variation in injury rates between the States. For males, the overall injury rates (per 10,000 persons) for Victoria, South Australia and Tasmania were in the range 11 to 16: those for Queensland and Western Australia were in the high 30s; whilst that for New South Wales exceeded 50. A similar ranking of injury rates prevailed in almost every subset. The highest rates arose in New South Wales, Queensland and Western Australia in six of the seven occupation groups, in nine of the ten industry groups and in all eleven age groups. It is difficult to find any scientific explanation for these variations in terms of levels or extent of exposure to risk. In the opinion of this author, these variations should be attributed to differences in the institutional arrangements for the coverage, collection and/or compilation of compensation data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253465 TI - Flawed foundation: a re-examination of the scientific basis for a dental benefit from fluoridation. AB - The scientific basis for a dental benefit from water fluoridation is critically examined. Professional responses and the "mind set" about fluoridation are described and discussed. PMID- 2253466 TI - Where there's smoke...carbon monoxide exposures in smoking and smoke-free workplaces. AB - Comparisons of expired air carbon monoxide levels in non-smoking staff in six licensed clubs (a smoking workplace) were made with those of non-smoking staff of a large public hospital (a smoke-free workplace). There was a significant difference between clubs and hospital in levels of CO at end of work. The average concentration of club workers was 8.7 ppm (Hospital, 5.3 ppm). Approximately one third of these non-smokers in licensed clubs exceeded 10 ppm putting them in the 'light smoker' category according to the manufacturer of the monitoring equipment. Club workers increased their CO level during work time by four times the increase of Hospital staff. This study suggests that there are significant gains to be made in reduction of intake of harmful passive-smoking products by removing tobacco smoke from workplaces. PMID- 2253468 TI - Commentary: 'What is to be done?' in public health. PMID- 2253467 TI - Parental help-seeking for behavioural and emotional problems in childhood and adolescence. AB - Previous publications from the Dunedin Multidisciplinary Health and Development Research Unit have reported the prevalence of DSM-III disorders through its longitudinal examination of a New Zealand birth cohort. The present study describes the help-seeking practices of each sample member's parents for their child's behavioural or emotional problems exhibited in childhood (ages 5-11) or adolescence (ages 12-15). Increased help-seeking for boys was evident in childhood. However, this sex difference was not present at adolescence. There was a decline in the frequency with which medically oriented agencies were contacted between childhood and adolescence, and teachers were found to be the most frequently used source of assistance in adolescence. Although there was a strong association between help-seeking and mental health disorder, approximately half of those with disorder had parents who had not sought help for their child's problems. In addition, family characteristics of low SES, low family social support and poorer maternal mental health predicted help-seeking. The results are discussed in terms of service provision for these age groups, within the present restructuring of the public health system in New Zealand. PMID- 2253469 TI - Comparison of respiration in rat, guinea pig and muskrat heart mitochondria. AB - 1. Subsarcolemmal and interfibrillar mitochondria were isolated from the hearts of the diving muskrat and non-diving guinea pig and rat. Respiration rates, respiratory control ratio (RCR) and phosphorous to oxygen (P:O) ratios determined. 2. There was no significant difference in these values among the three species or between mitochondrial populations. 3. Mitochondrial yield as measured by citrate synthase of whole heart homogenates was greatest in the rat, intermediate in the muskrat and lowest in the guinea pig. 4. Muskrat heart mitochondria do not differ from rat and guinea pig heart mitochondria in the ability to use pyruvate as a substrate. 5. Differences in heart mitochondrial function between diving and non-diving rodents were not found and thus do not appear to be adaptations for the hypoxia of diving. PMID- 2253470 TI - Catalatic capacities in heat-shocked Euglena cells. AB - 1. Various heat treatments were applied to the wild strain Z. Klebs. of Euglena gracilis. 2. Samples of cells were taken at day 1 of the culture at 26 degrees C in a 33 mM lactate medium, when the catalatic capacities of the catalase were highest. 3. They were either submitted to heat treatments (36 and 38 degrees C), or heat-shocks (40, 42 degrees C) or non-permissive heat stress (45 degrees C) for 15 min, 1 and 2 hr. 4. After a 2-hr 45 degrees C treatment the cells were unable to recover normal physiological functions. 5. Heat treatments between 36 and 38 degrees C decreased the catalatic capacities of cells, while heat-shocks at 40 and 42 degrees C strongly reinforced these capacities of hydrogen peroxide dismutation. 6. Having been heat-shocked at 42 degrees C for 2 hr, the cells became different from control cells: (a) after several months of culture, they displayed catalatic capacities increased by 65%; (b) they were able from now on to survive a 2 hr heat shock at 45 degrees C. PMID- 2253471 TI - Arterial fatty acid-binding protein activity associated with dietarily-induced and spontaneously occurring atherosclerosis in the rabbit (Oryctolagus cuniculus). AB - 1. Adult WHHL rabbits, or New Zealand rabbits fed either a stock chow diet or a high cholesterol diet were evaluated to assess the relationship between the development of aortic atherosclerosis and arterial FABP activity. 2. Aortic FABP activity was significantly (P less than 0.05) lower in atherosclerotic New Zealand aortas (0.039 +/- 0.008 nmol palmitoyl CoA bound/mg soluble prot) which had developed macroscopic lesions on 80% of the aortic surface as compared to lesion-free New Zealand aortas (0.053 +/- 0.002 nmol palmitoyl CoA bound/mg soluble prot). 3. In spontaneously hyperlipidemic rabbit (WHHL) aortas, FABP activity (0.023 +/- 0.004 nmol palmitoyl CoA bound/mg soluble prot) was significantly lower (P less than 0.05) than in either the normal or atherosclerotic New Zealand aortas. 4. To our knowledge, this study is the first to report a change in arterial FABP with the atherogenic process. PMID- 2253472 TI - Comparison of xanthine:NAD+ oxidoreductase from liver of two uricotelic species: hen Gallus gallus and snake Natrix natrix. AB - 1. Kinetic properties of xanthine:NAD+ oxidoreductase from liver of two uricotelic species of vertebrates (hen Gallus gallus and snake Natrix natrix) are compared. 2. Hen enzyme is saturated by hypoxanthine and xanthine at higher concentrations than the snake enzyme. For both species the enzyme-saturating concentration and hydroxylation rate of hypoxanthine are higher than those of xanthine, and the rate of uric acid production in the hypoxanthine----xanthine--- uric acid reaction sequence is independent of the initial hypoxanthine concentration. 3. Km's for xanthine are the same, but Km for NAD+ of the hen enzyme is approximately 5-fold lower. The enzyme from both species is inhibited by NADH only slightly and at high non-physiological concentrations. PMID- 2253473 TI - Xanthine:NAD+ oxidoreductase from embryo liver of hen Gallus gallus. AB - 1. Xanthine:NAD+ oxidoreductase from chick embryo liver is unconvertible to the O2-dependent form, as is the enzyme from the adult hen. The Km for NAD+ (approximately 3 microM) of the embryonic enzyme is equal to, and the Km for xanthine (approximately 5 microM) is 2.5-fold lower, when compared with respective Km values of the "adult" hen enzyme. The inhibition of embryonic enzyme by NADH begins at 10 microM NADH and attains 13% at 35 microM NADH (respective data for the "adult" enzyme: 50 microM and 20% at 80 microM NADH). 2. The course of hypoxanthine----xanthine----uric acid hydroxylation catalyzed by the embryonic and "adult" enzymes is similar, however the rate of the first reaction is 2-fold lower for the embryonic enzyme. Under conditions of the limited nutritional system in the developing chick embryo, the low rate of hypoxanthine hydroxylation may promote reutilization of hypoxanthine for nucleotide synthesis. PMID- 2253474 TI - Effect of low and high temperatures on chymotrypsin from Atlantic cod (Gadus morhua L.); comparison with bovine alpha-chymotrypsin. AB - 1. Cod chymotrypsin displays higher enzyme activity compared to bovine alpha chymotrypsin when assayed at low temperatures (3-15 degrees C). 2. Both enzymes are inactivated when incubated at temperatures between 60 and 70 degrees C. 3. When incubated at 99 degrees C the cod enzyme retains about 50% of the initial activity measured at room temperature. 4. Preincubation at boiling temperature renders the cod chymotrypsin active at 70 degrees C whereas the bovine enzyme is rapidly inactivated. PMID- 2253475 TI - Inhibition of intrinsic protein tyrosine kinase activity of EGF-receptor kinase complex from human breast cancer cells by the marine sponge metabolite (+) aeroplysinin-1. AB - 1. (+)-Aeroplysinin-1, a naturally occurring tyrosine metabolite from the marine sponge Verongia aerophoba, was found to inhibit the phosphorylation of lipocortin like proteins by a highly purified preparation of the epidermal growth factor (EGF) receptor-tyrosine protein kinase complex from MCF-7 breast carcinoma cells. 2. (+)-Aeroplysinin-1 blocked the EGF-dependent proliferation of both MCF-7 and ZR-75-1 human breast cancer cells and inhibited the ligand-induced endocytosis of the EGF receptor in vitro. 3. Treatment with aeroplysinin-1 in the concentration range at 0.25-0.5 microM resulted in a time- and dose-dependent total tumor cell death in vitro. 4. At a 10-fold higher concentration the compound did not reveal any cytostatic activity in normal human fibroblasts. 5. From these data we conclude that (+)-aeroplysinin-1 represents a compound which displays a strong anti-tumor effect on EGF-dependent tumor cell lines. PMID- 2253476 TI - Studies on the energy metabolism of opossum (Didelphis virginiana) erythrocytes- VI. De novo purine nucleotide biosynthesis is limited to the final steps of the pathway in vitro. AB - 1. High pressure liquid radiochromatography was used to show the incorporation of [14C] formate with Z-compounds into ATP and GTP in opossum erythrocytes. 2. The use of Z-riboside with [14C] formate resulted in more extensive labeling of ATP than the Z-base/[14C] formate combination as substrates for nucleotide biosynthesis. 3. Substantial accumulation of ZMP and ZTP, but no ZDP was detected in the chromatograms. 4. ATP was unstable in red cells metabolizing in the presence of Z-compounds under an atmosphere of air as gas phase in these experiments. PMID- 2253477 TI - Biochemical and histochemical studies on skeletal muscle in rat during the course of development. The biochemical properties of type 2C muscle fiber. AB - 1. Biochemical and histochemical analyses were performed on skeletal rat muscles over the course of development from neonate to adult. 2. A small amount of triglyceride and a large amount of glycogen were found to be contained in neonatal type 2C muscle fiber; based on this finding the main energy metabolism in this fiber was thought to be anaerobic glycolysis. 3. Moreover at 10 days type 2C muscle fiber was shown to contain a large amount of triglyceride. 4. These results suggest that, although histochemical characteristics remain the same, biochemical properties change during the course of muscle development. PMID- 2253478 TI - Age-dependent variations in the camel lens crystallins. AB - 1. Water-soluble crystallins from cortex and nucleus of both young and adult camel lenses were fractionated by gel filtration into high molecular weight aggregate (HMW-aggregate), alpha-low, beta-high, beta-low, gamma-high and gamma low protein fractions. 2. Crystallins were characterized by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF). Changes related to age and lens parts were compared. 3. The major changes in crystallin distribution included an increase in HMW-aggregate (alpha-high), beta-high, and gamma, and a decrease in alpha-low and beta-low, when comparing lenses in the direction of the nucleus and in the direction of increasing age. 4. Similar changes were detected comparing either cortex and nucleus of the same lens or whole lenses of different age. PMID- 2253479 TI - The blue-green blood plasma of marine fish. AB - 1. The blue-green coloration of the blood plasma in some marine fishes, which is attributed to a protein bound tetrapyrrol (biliverdin), is an anomaly in vertebrates. 2. Recent studies have shown that biliverdin not only occurs in many fish, but is also present in the blood of tobacco hornworm, the wings of moth and butterfly, the shell of bird eggs, the serum and egg of frog, the placenta of dog and in the blood of humans suffering from hepatic diseases. 3. In this review, we begin with a historical account of the description of the presence of blue-green blood plasma in fish, and then consider the biochemistry, metabolism, physiology, and the ecological implications of biliverdin in fish. 4. A comparative description of the occurrence of biliverdin in fish and other animals is presented. 5. The mechanism of accumulation of biliverdin in fish blood and its evolutionary significance are also considered. It is suggested that this process may serve as a useful model for further research on bile pigment metabolism in other animals. PMID- 2253480 TI - The effect of temperature on catalytic function of glyceraldehyde-3-phosphate dehydrogenase from muscle of pig and carp Cyprinus carpio. AB - 1. The temperature dependence of the kinetics of glyceraldehyde-3-phosphate dehydrogenase from white muscle of carp and skeletal muscle of pig was examined. 2. The Km values of carp muscle enzyme were stable over the temperature range 5 35 degrees C, but increased for pig muscle enzyme with increasing temperature. 3. The Arrhenius plot for pig muscle enzyme is linear but non-linear for carp muscle enzyme. 4. The differences indicate that glyceraldehyde-3-phosphate dehydrogenase from white carp muscle may contribute to the adaptive mechanism of carp to varied temperature conditions. PMID- 2253481 TI - ApoVLDLII gene transcription in immature cockerels without estradiol stimulation. AB - 1. Previous studies have led to the conclusion that the gene encoding the apo very low density lipoprotein II (ApoVLDLII) is under full estrogen control. However, by using a sensitive hybridization technique we found a weak expression of this gene in some males in the absence of hormone. 2. As the vitellogenin II gene, which is also estrogen dependent, remains inactive in these animals it is likely that they carry a deregulated allele of the ApoVLDLII gene. 3. The highest level of ApoVLDLII mRNA is found in genetically fat males suggesting a possible involvement of the ApoVLDLII gene in fatness determinism. PMID- 2253482 TI - Comparative studies on lipogenic enzyme activities in brown adipose tissue and liver of the rat during starvation-refeeding transition and cold exposure. AB - 1. The effect of starvation-refeeding transition and cold exposure on the activity of lipogenic enzymes in brown adipose tissue (BAT) and liver from rats was compared. 2. Starvation caused a decrease of lipogenic enzyme activities in BAT and liver. 3. Refeeding of the animals with a high carbohydrate diet caused an increase of lipogenic enzymes in these tissues. 4. Cold exposure (4 degrees C for 30 days) led to the increase of BAT enzyme activities to the values observed in rats fed a high carbohydrate diet. 5. Under the same conditions the activity of hepatic lipogenic enzymes also increased but never reached the values observed in the liver of rats fed with a high carbohydrate diet. 6. Therefore BAT and liver lipogenic enzymes showed, in general, a similar pattern of variation under identical nutritional conditions, but substantial differences between these two organs occurred as far as the response to cold exposure was concerned. 7. The experiments also revealed that in the control animals BAT displayed a higher lipogenic potential than the liver. PMID- 2253483 TI - Effect of dietary cholesterol on the lipoprotein profile and binding of radioiodinated lipoproteins to hepatic membranes in the cockerel (Gallus domesticus). AB - 1. Cockerels fed a cholesterol-supplemented diet experienced a marked elevation of lipoprotein particles of density less than or equal to 1.006 g/ml (VLDL) and a diminution of lipoprotein particles of density 1.02-1.05 g/ml (LDL). 2. Unlike VLDL of some cholesterol-fed animals, cholesterol-fed cockerel VLDL did not display beta-mobility on agarose gel electrophoresis. 3. [125I]LDL and [125I]HDL binding to cockerel liver membranes was not affected by cholesterol feeding. 4. Different lipoprotein types appear to bind to a common site on cockerel liver membranes. 5. The results suggest that liver cells of cockerels may not possess LDL binding sites that are analogous to those of mammalian species. PMID- 2253484 TI - Molecular characteristics of pepsinogen and pepsin from duck glandular stomach. AB - 1. Two procedures were developed for the preparation of duck pepsinogen, an enzyme from the family of aspartic proteases (EC 3.4.23.1) and its zymogen. 2. The amino acid composition, sugar content and the partial N- and C-terminal sequences of both the enzyme and the zymogen were determined. These sequences are highly homologous with the terminal sequences of chicken pepsin(ogen). 3. Duck pepsinogen and pepsin are unlike other pepsin(ogen)s in being relatively stable in alkaline media: pepsinogen is inactivated at pH 12.1, pepsin at pH 9.6. 4. Duck pepsin is inhibited by diazoacetyl-D,L-norleucine methyl ester (DAN), 1,2 epoxy-3(p-nitrophe-noxy)propane (EPNP), pepstatin and a synthetic pepsin inhibitor Val-D-Leu-Pro-Phe-Phe-Val-D- Leu. The pH-optimum of duck pepsin determined in the presence of synthetic substrate is pH 4. 5. Duck pepsin has a marked milk-clotting activity whereas its proteolytic activity is lower than that of chicken pepsin. 6. The activation of duck pepsinogen is paralleled by two conformational changes. The activation half-life determined in the presence of a synthetic substrate at pH 2 and 14 degrees C is 20 sec. PMID- 2253485 TI - Cellular and biochemical aspects of muscle differentiation. PMID- 2253486 TI - L-dopa decarboxylase in Ceratitis capitata white puparia and human: a comparative study. AB - 1. L-DOPA decarboxylase (DDC) from Ceratitis capitata and from human kidney have been purified by the same methodology. 2. Both enzymes show mol. wts of 100,000, consisting of two identical mol. wt subunits and solely decarboxylate L-DOPA. 3. In the presence of 5-hydroxytryptophan (5-HTP) only the DDC activity from human kidney is remarkably reduced. 4. Addition of exogenous coenzyme is essential only for human DDC activity. 5. Polyclonal antibodies, raised against DDC purified from insects or humans, cross-react with both antigens. PMID- 2253487 TI - Elevated hepatic mitochondrial oxidative capacities in cold exposed rats. AB - 1. Hepatic mitochondrial oxidative capacities were studied in rats exposed to cold for periods ranging from 5 to 15 days. The mitochondria obtained in this study were well coupled as shown by RCR and ADP/O ratios. 2. The liver mitochondria of cold exposed rats showed significantly increased respiratory rates (ng atoms of oxygen consumed min-1 mg prot-1), starting from day 10 of cold exposure, using lipid and non-lipid substrates. 3. For non-lipid substrates, the elevated respiratory rates found in the mitochondria could indicate an increased capacity to oxidize these substrates. For the lipid substrate, on the other hand, an enhanced oxidation through Krebs-cycle of a part of acetyl-CoA otherwise utilized to form ketone bodies, could also occur. 4. Taken together the results suggest that, during cold exposure, liver mitochondria could participate in cold adaptation mechanisms, by improving ATP production. PMID- 2253489 TI - Toxocariasis. PMID- 2253488 TI - Pyruvate sparing by butyrate and propionate in proliferating colonic epithelium. AB - 1. The effects of fasting and fasting followed by refeeding on the relative activities of the pyruvate dehydrogenase (PDH) complex and the tricarboxylic acid (TCA) cycle in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]pyruvate and [3-14C]pyruvate, respectively. 2. Decarboxylation of pyruvate by the PDH complex exceeded that by the TCA cycle in both fasted and fasted/refed colonocytes, was higher in distal than in proximal colon, and was stimulated by refeeding following a fast. 3. Oxidation of pyruvate by both the PDH complex and the TCA cycle was inhibited by butyrate. 4. Propionate alone had no effect, but synergized with butyrate to further reduce pyruvate decarboxylation by the TCA cycle. 5. Preferential utilization of butyrate by proliferating colonic epithelial cells is postulated to maximize the energy yield and spare pyruvate and its precursors for alternative synthetic roles necessary for active cell division. PMID- 2253491 TI - Care of the elderly. Who cares? PMID- 2253490 TI - Care of the elderly. The best solution. PMID- 2253492 TI - Constipation. PMID- 2253493 TI - Behavioral treatment in pediatrics. PMID- 2253494 TI - Interstitial fluid concentrations of ceftriaxone (1 g.i.v.) in the subperitoneal space after hysterectomy. AB - The ability of an antibiotic to penetrate into the extravascular site of infection is particularly important for a successful perioperative antibiotic prophylaxis and postoperative therapy of bacterial infection. We, therefore, measured interstitial fluid concentrations of ceftriaxone in the subperitoneal space following hysterectomy using Rubinstein's disc method after intravenous administration of 1 g of ceftriaxone preoperatively. After removal of the uterus, two disc units were implanted intraoperatively in the right and left subperitoneal space of 16 patients and were drawn out through the open vaginal cuff after given periods of time. Five disc and blood specimens were obtained after 90 min and 2, 6, 12, 24, and 48 h, respectively. Ceftriaxone concentrations were determined by bioassay. After administration of 1 g of ceftriaxone, interstitial fluid concentrations following hysterectomy were above the MIC90 of most pathogens encountered in gynecologic infections over a period of 24 h. PMID- 2253495 TI - Penetration of aminoglycosides into human peritoneal tissue. AB - Each of 30 patients underwent elective laparotomy following administration of a single intravenous dose of amikacin, netilmicin or tobramycin. Therapeutic concentrations of amikacin were achieved in peritoneal tissue in 10/10 patients. Only 13/20 samples from patients receiving the other two antibiotics showed antibacterial activity. Our data suggest that the penetrability of tobramycin (53%) and amikacin (39%) into the uninflamed peritoneal tissue is superior to that of netilmicin (16%). PMID- 2253496 TI - Relevance of protein binding to cephalosporin antimicrobial activity in vivo. AB - Protein binding, serum kinetics and minimum inhibitory concentrations (MICs) for Staphylococcus aureus were determined for cefoxitin, cefazolin, ceftazidime and ceftriaxone in the rabbit. MICs of cefazolin and cefoxitin were also measured for Escherichia coli. Varying concentrations of the bacteria were administered intradermally to create areas of cellulitis, which were quantified as mean erythematous areas (EAs). Despite large differences in protein binding of the antibiotics (range 12-88%) and antibiotic dosing to allow serum concentrations to drop below the respective MICs, there was no statistical difference in the mean EAs of the animals after bacterial challenge. Antibiotic protein binding did not alter the course of cellulitis nor correlate with bacterial MIC in this model. PMID- 2253497 TI - Influence of temperature on beta-lactamase production and outer membrane proteins in gram-negative rods. AB - The influence of temperature (ranging from 28 to 42 degrees C) was studied on the phenotypic expression of chromosomally mediated beta-lactamases in gram-negative clinical isolates and in their beta-lactamase-depressed resistant counterparts. The enzymes were expressed most intensely at lower temperatures (28 or 32 degrees C). In most strains the enzyme was barely detectable at growth temperatures of 42 degrees C independent of the inducer employed. The release of the enzyme into the surrounding medium was marginal even at a growth temperature of 42 degrees C. The major outer membrane proteins revealed discrepancies dependent on the growth temperature only for the Providencia rettgeri W 862 strain. Thus, it can be concluded that the phenotypic expression of chromosomal beta-lactamase is temperature dependent to the effect that the enzymes are most expressed at 28 or 32 degrees C. This agrees well with the increased susceptibility to most beta lactams due to the lowered beta-lactamase production at higher temperatures. This effect was pronounced most strikingly in Proteus vulgaris. PMID- 2253498 TI - Comparison of the effects of intra-arterial and intravenous cisplatin on both limb tumor and lung metastases of transitional cell carcinoma RBT-1 in rats. AB - The effects of intra-arterial (i.a.) and intravenous (i.v.) cisplatin on both limb tumor and lung metastases of transitional cell carcinoma RBT-1 in rats were compared. Tumor weights of limb tumors and the amount of lung nodules were evaluated on the eighth day after chemotherapy experiments. Both cisplatin 5 mg/kg i.a. and 5 mg/kg i.v. were administered to rats, but the intra-arterial method showed a significantly better effect on the limb tumor, whereas the intravenous method tended to be more effective on the lung metastases. Using the same dosage (5 mg/kg), the intra-arterial cisplatin group demonstrated a weaker level of nephrotoxicity and a smaller loss of body weight than seen in the intravenous cisplatin group. When a higher dose of cisplatin (6 mg/kg) was administered in the intra-arterial group, the antitumor effect on lung metastases and nephrotoxicity were similar to those of the group given cisplatin 5 mg/kg i.v. These data suggest that the dose of intra-arterial cisplatin can be slightly higher than that of intravenous cisplatin. Subsequently, a similar antitumor effect on lung metastases and a significantly better antitumor effect on primary tumor may be obtained at the equitoxic level. PMID- 2253499 TI - Combinations of antifungal and antineoplastic drugs with interactive effects on inhibition of yeast growth. AB - Interactive effects among antifungal and antineoplastic drugs contributed to toxicities when combinations of these drugs were used to inhibit the growth of five Candida spp. Drug interactions were measured by growth inhibition in both liquid and solid media, by viable cell counts and by examination using scanning electron microscopy. Large cooperative effects on toxicity were demonstrated between some antineoplastic and antifungal drugs. For example, positive cooperativity was seen between the antineoplastic drug 5-fluorouracil and combinations of the antifungal agents amphotericin B and miconazole nitrate. Smaller, and often negative, interactions occurred between the antineoplastic drug cyclophosphamide and antifungal drugs. The levels of drugs required for inhibition in combination drug treatments were critically dependent upon the ratios as well as the absolute concentrations of the drugs tested. Drug combinations were selected which inhibit yeast growth at concentrations far below the individual MIC of the drugs. These combinations may prove of value in clinical treatments of cancer patients infected by Candida. PMID- 2253500 TI - Chinese patients with transient ischemic attacks. AB - In 123 cases of transient ischemic attacks, 72 were followed up for 22 years. The percentage of complete stroke was 46.5% and the fatality rate 47.9%. Causes of death, survival rate by life table, limitation of indication of neurovascular surgical operation and rehabilitation of survived patients were studied. The causes of death were mainly cerebral strokes. The long-term follow-up showed that the range for neurovascular surgical operation was limited to only 17.9%. The 95% confidence interval of the 20-year survival rate was 17.7-53.6%. Ninety-four, 48 and 44 cases were examined by B-mode Doppler tomography, cerebral CT scanning and echocardiography, respectively. PMID- 2253501 TI - [Follow-up study of outcome of schizophrenia]. AB - In May to October, 1984. Jieyany County psychiatric epidemiology research group follow-up the patient 2545 cases (1979-1984) of schizophrenia. 27 cases were transfer to other localities (1.06%), 17 cases were missing (0.67%), 206 cases were dead (8.09%), 280 cases (11.00%) changed diagnosis in there years, and 2015 cases (79.17%) were followed. In this paper, the current condition of morbidity, the outcome and relation between the morbidity and prognosis were analysed. Results of present investigation show that fully recover from increased and social influence decreased as a results of conducting family therapy social prevention and support. PMID- 2253502 TI - [A preliminary exploration of the factors of some early family environment in schizophrenia]. AB - The relations between the factors of some early family environment and the psychosis in 200 cases of schizophrenia and 50 cases of argunic psychosis were studied with a comparison. As a result, a significant difference was showed (chi 2 = 5.06, P less than 0.05), OR = 4.18, and the confidence limit of 95 per cent was 1.20 to 14.51. It's considered that these factors are closely related to schizophrenia. PMID- 2253503 TI - [Analyzing MMPI examination in patients with neurosis by the criteria of Chinese T score]. AB - In the present paper, the results are summarized of MMPI measurements in 210 cases of neurosis. They, by the criteria of Chinese T score, show an increase in the scales 1, 2, 3 and 7 and have an identical rate of 87.5%. Hence, it is reasonable for the scales above to be designated as the coding model of neurosis. In every type of neurosis the scales 1, 2, 3 and 7 have a tendency to increase, but there is a slight difference in their highest point and kurtosis. In depression neurosis, neurasthenia and anxiety neurosis the scale 2 (D) increases dominantly; in hysteria, the scale 3 (HY); in hypochondria, the scale 1 (HS); in phobic and compulsion neurosis, the scale 7. Therefore, MMPI measurements can be useful for clinical classification of neurosis. PMID- 2253504 TI - [A controlled study of recent memory disturbance in patients with cerebral arteriosclerosis]. AB - "The Clinical Memory Test" was administered to 40 elderly patients with cerebral arteriosclerosis (group A), compared with 40 aged subjects as control (group B), all subjects of both groups were over 60 year old. The results indicate: MQ, directed memory, free recall of pictures and paired-association learning in group A were found significantly less than in group B. This shows the ability of active recall, memory and learning of abstract ideas decreased in the patients of cerebral arterlosclerosis, but it's only quantitative difference between groups A and B, there was not qualitative difference. PMID- 2253505 TI - [Clinical analysis, heredity and follow-up studies of mental retardation with schizophrenia]. AB - 58 cases of mental retardation with schizophrenia and 60 cases of schizophrenia had been studied in family, clinically analysed and followed up. It was found that there were statistical differences between two groups in forms of onset, age at onset, frequency of symptoms, time of acted effectiveness, out-come and morbidity risk of first degree relative etc. PMID- 2253506 TI - [Determination of plasma factor VIII-related antigen in patients with cerebrovascular disease]. AB - The associated antigen of factor VIII in plasma of 124 cases of cerebrovascular disease and 40 normal cases were detected using immune rocket electrophoresis. There were significant differences between the 3 illness groups and the normal group. The results suggest that the associated antigen of factor VIII may be one of the useful markers for forecasting the danger of cerebrovascular disease. PMID- 2253507 TI - [Inherited relationship of levels of serum lipid and lipoprotein in nuclear families in patients with arteriosclerotic stroke]. AB - This report presents the study on inherited relationship of levels of lipids and lipoprotein in 20 nuclear families of patients with arteriosclerotic stroke through application of analysis of correlation and regression. The results showed that the levels of serum lipids between spouses had little or nearly no correlation; and that between mid-parent and their children had positive or significant positive correlation, and so did that between siblings. It seems that the genetic factor have an important influence on levels of serum lipids in members of nuclear families of patients with arteriosclerotic stroke. PMID- 2253508 TI - [Lipid storage myopathy. Report of 2 cases]. AB - This paper reports two cases of lipid storage myopathy. Light microscopic studies of muscle biopsy materials showed excessive amounts of neutral fatty droplets under oil red O staining. Electron-microscopic studies showed that the fatty droplets were situated in the myofibrils, under the sarcolemma or even in lines. Symptoms of the patients were improved after treatment with prednisone. The clinical, pathological and electromyographic characteristics of both types (I and II) of lipid storage myopathy are reviewed. PMID- 2253509 TI - [A pathological and clinical study of cerebral embolism]. AB - 16 specimens of cerebral embolism were studied with regard to their pathological and clinical manifestations. Close observations were made in 35 foci of infarction and 24 emboli in 14 specimens, among which 5 were multi-embolic. Most of the embolism were located at the bifurcations of the middle cerebral arteries. The emboli in 11 specimens were confirmed to be cardiogenic and in 1 specimen to be neoplastic. 7 specimens and twelve emboli were examined under the scanning electron microscope. It was found that the pathological appearances of the emboli varied and there were tiny spaces inside the embolized arteries. This might facilitate the embolus to get organized. PMID- 2253510 TI - [Analysis of the high-resolution real-time sonographic images of the carotid bifurcations in normal adults]. AB - The high-resolution real-time sonographic images in 186 carotid bifurcations (CB) of 93 selected normal persons were quantitatively analysed for 9 parameters including the diameters of the internal carotid arteries (CCA), the bifurcating angles of the ICA and ECA, and the angles between the ICA and ECA. The results of all the measurements were analysed with the relevant statistical methods. The normal field (99% limit) of CB in every age group was shown in this paper. The normal range of the measured values of the carotid bifurcations in each age group was calculated, and the laws governing their changing trends and their clinical significance were discussed. PMID- 2253511 TI - [A clinicopathological analysis of 12 cases of cerebrovascular leptospirosis]. AB - 12 pathologically verified cases of cerebrovascular leptospirosis were analysed of its clinical characteristics and types. Formation and development of cerebral panarteritis and infarctions were also discussed. It occurred in rural areas among children and adolescents after infection by leptospira pomona, especially following latent infection. Multiple occlusive vascular disorder presenting as a late manifestation of pomona infection occurred in 9 cases, intracranial hemorrhage in 2, and intracranial hypertension in 1 case. Cerebral panarteritis involved the main trunks of larger arteries at the base of the brain. Owing to invariable narrowing of intracranial portions of internal carotid arteries, infarcts always appeared in areas supplied by the middle cerebral artery, often accompanied by marginal infarction at watershed areas. It was suggested that cerebrovascular leptospirosis could be ascribed to residual infection of cerebral arteries soaked in CSF during the septicemic stage of pomona infection. PMID- 2253512 TI - [Pathologic observations on the peripheral nerves in simple polymyositis]. AB - In 6 cases of polymyositis was performed muscle and sural nerve biopsy. All the 6 patients presented typical clinical pictures of simple polymyositis. Sural nerves showed demyelination and axonal changes, under light and electron microscopy. It seems that simple polymyositis accompanied by the alterations in peripheral nerves is not very rare. In 3 cases, a few small arteries in the interfascicular areas of the nerves were nearly totally occluded due to the intimal proliferation. Clinical examination revealed no evidence of systemic vasculitis. On the basis of these data, the authors suspect that the above mentioned pathological findings probably are partial presentations among the spectrum of allergic disorder, which presents many clinical types and various combinations. PMID- 2253513 TI - [Intracerebral tuberculomas. A CT study of 14 cases]. AB - The clinical manife stations and CT scans of 14 cases of intracerebral tuberculomas were reviewed. 9 cases were associated with tuberculous meningitis. The images of the tuberculomas on CT scans appeared to be disc-like, ring-like or irregular in shape. The irregular mass consisted of multiple discs or rings coalescing to produce such irregular contours. On the plain scans, fewer of the tuberculomas showed images of low density or isodenseimages they became clear images of high density on the enhanced scans. Of the 5 cases not associated with tuberculous meningitis, 3 had epilepsies. The experience obtained in recent years indicated that the majority of tuberculomas could decrease in size or completely reabsorbed with adequate antituberculous medications. For the treatment of intracerebral tuberulomas it was recommended to use regular doses of Isoniazid, Rifampin, Ethambutol and other antituberculous drugs in combination for one to one and half years. Surgery should be performed when necessary. PMID- 2253514 TI - [A comparison of myodil and omnipaque as contrast media in myelography]. AB - The myelographic results of 30 cases in each group using myodil and omnipaque respectively were compared. As far as intraspinal extramedullary lesions were concerned, the diagnostic value of either contrast medium was almost the same. If CT scan was used along with omnipaque myelography, the fine structural changes could better be observed. As to the intramedullary lesions of the spinal cord, both contrast media seemed to be of less diagnostic value even though CT scan was used together. This was especially true in cases of demyelinating lesions. But it seemed to the authors that the number of the cases studied was too small to draw a definite conclusion. The side effects and toxicity of omnipaque as a contrast medium in myelography were less than those of myodil. However, myodil myelography might be useful and not abandoned in those areas where local economic conditions and facilities were less favorable. PMID- 2253515 TI - [Clinicopathological features and immunohistological diagnosis of olfactory neuroblastoma]. AB - Nasal olfactory neuroblastoma and other malignant neoplasms showing spherical cell are easily confused in clinical and pathological diagnosis. We have made immunohistochemical staining in 7 olfactory neuroblastoma cases. Results showed that they were all positively stained by NSE, and negatively by keratin, leucocyte common antigen, desmin and S-100 protein (except 1 positive by desmin). We believe that the olfactory neuroblastoma cells are uniform morphologically. The cells are round, elliptic, having scant cytoplasm; with coarse or fine chromatin. Neurofibers can be found among tumor cells. Their histological structures vary greatly. They may form nest or garland, and they may also form striation, cleft or discrete structure; but rosette or pseudo-rosette structure is uncommon. PMID- 2253516 TI - [Significance of GABA-energic system in the central nervous system in clinical psychologic medicine]. PMID- 2253517 TI - [Inhibitory effects of Phyllanthus emblica juice on formation of N nitrosomorpholine in vitro and N-nitrosoproline in rat and human]. AB - The juice of Phyllanthus emblica and its dialyzate were examined for their inhibition on formation of N-nitrosomorpholine (NMOR) in vitro and N nitrosoproline (NPRO) in vivo. Addition of 2 ml of the juice dialyzate (JD) to a system containing 22 mumols/L NaNO2 and 22 mumols/L morpholine was found to effectively block NMOR formation, with the inhibition of 93%, while only 49.2% of inhibition was observed from the low concentration of vitamin C (VC, 20.5 mumols/L), which is equal to those present in the JD. Moreover, the inhibition was not affected by precipitating JD with plumbous acetate and gelatin. In rats garaging with NaNO2 and proline (40 mumols/L), co-administration of 1.3 ml of the undialyzed juice containing 36 mumols/L of VC reduced the urinary excretion of NPRO from 69.62 nmol/L to 4.24 nmol/L. Similarly, it was found in human studies that 13 ml of the juice dramatically diminished the NPRO excretion from 75.10 nmol/L to 22.79 nmol/L in the 24-hr urine of 12 healthy volunteers, who had ingested 300 mg NaNO3 and 500 mg proline. Again, the juice showed a higher inhibition in both cases in inhibiting NPRO synthesis than the equivalent of VC solution. The results suggested that only a fraction of inhibition is accounted for by VC in the juice, whereas the rest might contribute to some unknown non phenolic inhibitors, which are worthwhile further identifying. PMID- 2253518 TI - [The determination of DNA adducts in liver and lung of mice exposed to dimethylnitrosamine]. AB - The purpose of this study was to assess the role of dimethylnitrosamine (DMN) in DNA lesions and to determine the levels of O6-methyl-guanine (O6-mGua) and N-7 methyl-guanine (m7-Gua). Mice were treated with 10 ppm DMN in drinking water for 1, 2, 4, 8, 16 and 32 days. The average dosage of DMN was 2 mg/kg/day, DNA was isolated from liver and lung specimens, and its purine bases separated by high performance liquid chromatography with fluorescence detection. The results showed the presence of O6-mGua and m7-Gua in the DNA following administration of DMN. The m7-Gua was found to be unsteady. O6-mGua decreased rapidly after 1 and 2 days treatment with DMN, but was raised after 32 days with continuous exposure. These findings suggest that damaged DNA would be repaired in vivo, but with continuous exposure to DMN, O6-mGua would accumulate in the DNA and this might be the cause of tumor induction. PMID- 2253519 TI - [Comparative ability of three aniline derivatives to alter biotransformation enzymes in rat liver]. AB - The effect of 4,4'-methylene bis (2-chloroaniline) (MOCA), 4,4'-methylene dianiline (MDA) and 4,4'-sulfonyl dianiline (Dapsone) on xenobiotic biotransformation in vivo was studied in male rat liver. Treatment with MOCA and MDA caused a dose dependent increase in ethoxyresorufin O-deethylase activity and concomitant decrease in aldrin epoxidase activity. Treatment with MOCA and MDA also resulted in increases in ethoxycoumarin O-deethylation and epoxide hydrolation while only MOCA induced cytosolic glutathione S-transferase activity. Treatment with Dapsone resulted in no changes in xenobiotic biotransformation except for the induction of aniline hydroxylation. The results are consistent with the contention that there is a relationship between carcinogenic chemicals and particular alteration in the activities of biotransformation enzymes. PMID- 2253520 TI - [Experimental research on toxic reaction of rats to sodium fluoride after a short period of exposure]. AB - This article reported the effects of 3 different dosages of NaF on the rats when they were exposed for 30-90 days. The results showed that many toxic indexes had significant changes when high dose of NaF (3.37 mg/kg) was given to rats for 30 days. Some toxic indexes had significant changes when medium dose of NaF (1.12 mg/kg) was given to rats for 90 days. But no significant difference was observed when compared to the normal control group, when low dose of NaF (0.37 mg/kg) was given to rats for 90 days. PMID- 2253521 TI - [Case control study of child obesity]. AB - Using 1:1 matched Logistic regression model to study the etiology of 80 obese children, we find the Kaup's index of their parents, birth weight and breast feeding were the risk factors of child obesity. On the other hand, we find the basal metabolic rate of obese children was not different from that of controls. Besides, as to the extent of obesity, we find the earlier obesity occurred (age less than or equal to 4 years) the more severe were they than that of the latter one (age greater than 4 years) because the etiology of these two types was different. The former was associated with prenatal factors while the latter with feeding types. In this study, we also find the skeletal age of obese children was advanced the systolic and diastolic blood pressures were higher and the cardiovascular and respiratory functions weakened. PMID- 2253522 TI - [A study on investigation of an outbreak of Paederus dermatitis in the city of Yantai]. AB - This paper reports on an outbreak of paederus dermatitis occurring the Chinese Coaleconomy College at the suburbs of Yantai in September 1987. The incidence rate was 35.02 percent. The clinical characteristics of paederus dermatitis were described and the ecology of paederuses was studied. That provided scientific basis for prevention and treatment of this disease. PMID- 2253523 TI - [Investigation of the water quality of Yalu Zangbo Jiang and the well-water of towns along it]. AB - This article reports for the first time results of investigation on the water quality of the Yalu Zangbo Jiang and the wells-water of towns along it. It analysed such items of the water quality as pH, temperature, turbidity, total hardness, chloride, sulphate, nitrogen nitrate, fluoride, iron, manganese, zinc, copper, cadmium, lead and arsenic. The data indicated clearly that the turbidity and iron content of the river water and some of the wells were higher, but total hardness and fluoride content were lower, while other items analysed all conformed to the country's hygienic standard. Generally speaking, the hygienic standard of the water quality of the Yalu Zangbo Jiang, and the wells' water of towns along it is fairly good. PMID- 2253524 TI - [The investigation of air ion and particulates condition in Tianzhu Mountain]. AB - In order to monitor the distribution of atmospheric air ion and particulates in Tianzhu Mountain region, two observation points were established in Tianzhu Mountain in April, 1989. The results showed that the average concentration of air anode ion was 680/cm3, cathode ion 650/cm3. the range of single electrode coefficient is comfortable feeling, air quality index is 0.71 up to standard B grade (clean air), Total average concentration of suspended particulates was 0.242 mg/m3, average concentration of inhalation particulates was 0.168 mg/m3. Seventy percent particulates had diameters less than 10 microns, and thirty percent greater than 10 microns in total suspended particulates. PMID- 2253525 TI - [Effects of covering the windowpane with plastic film on microclimate and sunshine of the living room in a cold region]. AB - Experiments were made to ascertain the effects of covering windowpane with plastic film in Hulunbeir region on microclimate and sunshine intensity in the living room. It was found that a good regulative effect on the room microclimate resulted by covering the windowpane with plastic film in the cold region. The room temperature rose distinctly. No evident effects were found on ultra-violet radiation and illumination. But the concentration of carbon dioxide increased to some extent. Attention should be paid to ventilation of the room. PMID- 2253526 TI - [Accidental methyl alcohol poisoning]. AB - An accidental poisoning due to drinking methyl alcohol in Chaoyang county is reported, analysing the accident. The poison came from the "retail white spirit" which was contaminated with methyl alcohol. Twenty-nine persons drank the wine, fourteen of them died, two of them became blind. After drinking this "retail white spirit" the drinkers showed symptoms of vertigo, headache, weakness, vomiting, night sweat, dyspnea and blurring of vision etc. within 6-120 hours. On examining the remaining spirit, we found the content of methyl alcohol to be between 16.6 and 40.69 g/100 ml. Some of the patients' urine and blood also contained methyl alcohol. We reckoned that each one of the twenty patients had taken more than 27 g of methyl alcohol and each of the ten dead drank more than 40 ml of the alcohol. PMID- 2253527 TI - Chest pain with normal coronary arteries. Another perspective. PMID- 2253528 TI - Edrophonium provocative test in noncardiac chest pain. Evaluation of testing techniques. AB - Edrophonium chloride is used frequently as a provocative agent in the assessment of noncardiac chest pain (NCCP). However, the optimum dose and most appropriate method of interpreting test results is controversial. We studied 150 consecutive NCCP patients and 50 age-matched controls who alternately received either 80 micrograms/kg or 10 mg intravenous bolus doses of edrophonium preceded by saline placebo injections. Distal esophageal pressures were measured before and after drug injection in response to ten 5-cc wet swallows. Following 10 mg of edrophonium, 33% of patients and 4% of controls reported chest pain, while 29% of patients and no controls receiving the 80 micrograms/kg dose complained of chest pain. Amplitude changes after either dose were not significantly different for all comparisons, but the duration of response did distinguish the two doses in patients with chest pain. A significantly greater (P = 0.01) increase in distal contraction duration occurred after 10 mg (74 +/- 12%; +/- SE) compared to 80 micrograms/kg dose (43 +/- 6%). However, individual responses to the two doses overlapped considerably. If a positive test is redefined to include both chest pain and manometric changes that are significantly different from controls, the positivity rate changes drastically; 33% to 9% in the 10-mg group and 30% to 3% in the 80-micrograms/kg group. Side effects were similar between doses, but there was a significant (P = 0.02) linear relationship between intensity of side effects and the edrophonium dose per kilogram of body weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253529 TI - Patterns of dyspepsia in patients with no clinical evidence of organic diseases. AB - We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis. PMID- 2253530 TI - Pyloric deformation from peptic disease. Radiographic evidence for incompetence rather than obstruction. AB - We have used double-contrast radiographic techniques to clarify what changes in the configuration and movements of the gastroduodenal junction result when peptic lesions involve the distal gastric segment between the proximal (PPL) and the distal pyloric muscle loop (DPL). Among 50 cases of pyloric ulceration diagnosed during a four-year study period, 18 cases fulfilled all study criteria. Ulcers maintained a consistent location with regard to the muscular structures of the pylorus, and by affecting these structures, led to many strange deformations of the gastric outlet including permanent pseudodiverticula and reversal of pyloric angulation. The most common site for peptic lesions in the pyloric segment was the protuberance of the lesser curvature called the pyloric torus; many torus lesions extended into and destroyed the DPL. This led to widening of the gastric outlet and radiographic evidence of increased duodenogastric reflux. Pyloric closure was further impaired in this setting because the mucosa no longer prolapsed into the gastric outlet and did not occlude the pyloric lumen as it normally does. Less common lesions involved the greater curvature and the PPL. In one patient, scarring of the PPL led to an antral web and gastric hyperperistalsis. This was the only patient who required operation for chronic gastric outlet obstruction. One-third of the 18 patients had reflux esophagitis in addition to peptic pyloric disease. In most patients without additional ulcerogenic risk factors, treatment with antisecretory agents led to the healing of ulcer craters. We conclude that the morphologic and functional changes of the gastric outlet caused by peptic lesions depend, in part, on the effect the ulcer has on the underlying pyloric musculature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253531 TI - Human gastric mucosa expresses glandular M3 subtype of muscarinic receptors. AB - Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 +/- 6 fmol/mg protein and the tritiated ligand N methylscopolamine had an affinity of (KD) 0.39 +/- 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF DX 116 had low affinities of 148 +/- 32 nM (n = 13) and 4043 +/- 1011 nM (n = 3) KD, respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities of KD 78 +/- 23 nM (n = 5) and 5.6 +/- 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type. PMID- 2253532 TI - Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity. AB - Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24-hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitro of antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivo pH metry studies, because we found that the greatest absolute difference between raw fast acquired (4-6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1-A2; glass-glass, G1-G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland Altman technique for assessing measurement agreement, the differences between the 24-hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P = .903 and P = 0.824, respectively) and their 95% confidence limits are comprised within the range (+/-) of the reading error of the measuring systems (namely, +/- 0.3 pH units and +/- 12 mmol/liter in terms of [H+]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253533 TI - Cigarette smoking, gastric acidity and peptic ulceration. What are the relationships? AB - The influence of cigarette smoking on intragastric acidity was assessed in duodenal ulcer patients in symptomatic remission and in healthy volunteers in a retrospective study. Continuous 24-hr pH recordings in 150 nonsmokers and 174 smokers receiving placebo treatment were compared. Daytime intragastric acidity was higher in smokers with a median pH (interquartile range) of 1.56 (1.34-1.80) than in nonsmokers, who had a median pH of 1.70 (1.45-1.97) (P less than 0.001). There was no difference in 24-hr and nighttime median pH between the two groups. The small difference in daytime intragastric acidity in smokers and nonsmokers is unlikely to account for the increased prevalence of peptic ulcer disease in smokers. The analysis of smoking status in duodenal ulcer patients and healthy controls and males and females supports the general trend towards higher daytime acidity in smokers. Again, no differences in pH during the 24-hr or night period were found between the groups. The epidemiological and clinical correlation between smoking and duodenal ulcer disease is not adequately explained by increased intragastric acidity. PMID- 2253534 TI - Gastric mucosal PGE2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects. AB - PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia. PMID- 2253535 TI - Endoscopic comparison of cimetidine and sucralfate for prevention of naproxen induced acute gastroduodenal injury. Effect of scoring method. AB - Nonsteroidal antiinflammatory drug-induced gastroduodenal mucosal damage observed endoscopically is usually categorized as hemorrhages, erosions, or ulcerations. We undertook this study to determine whether the injury produced by a commonly prescribed NSAID, naproxen, could be reduced by cotherapy with sucralfate or cimetidine and to determine how dependent the differences in the degree of protection against mucosal injury measured were on the scoring system used. Four groups of 20 healthy volunteers with endoscopically normal gastric and duodenal mucosa received naproxen (500 mg twice a day) plus cimetidine (300 mg four times a day or 400 mg twice a day), sucralfate (1 g four times a day), or placebo for seven days. After seven days of therapy, a second endoscopy was performed. Separate scoring systems were used for the presence of hemorrhages, erosions, and a combination of both types of injury. There were significantly fewer mucosal hemorrhages present when naproxen and cimetidine were administered than when naproxen was administered with placebo or sucralfate (placebo vs 300 mg cimetidine, P = 0.04, and placebo vs 400 mg cimetidine, P = 0.006, placebo vs sucralfate, P = 0.26). Both cimetidine dosages resulted in significantly fewer hemorrhages than were present following cotherapy of naproxen and sucralfate (P less than 0.05). In contrast, there was no discernible difference in the mucosal injury between placebo and any drug or between any two active therapies when the injury was evaluated based on the presence of gastric erosions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253536 TI - Effects of cisapride on gastrointestinal transit in healthy humans. AB - It was the aim of this study to assess the effects of cisapride on gastrointestinal transit of solids in healthy humans. Twelve men received cisapride 10 mg or placebo orally four times a day in random, double-blind, crossover fashion. Transit measurements were performed with a new gamma camera technique. Cisapride reduced mean gastric emptying time of 99mTc-labeled cellulose fiber [0.77 (0.69-1.12) hr [median (range)] vs 0.98 (0.63-1.95) hr; P less than 0.05] and 1- to 2-mm 111In-labeled plastic particles [1.08 (0.50-1.42) hr vs 1.69 (0.59-3.03) hr; P less than 0.01]. Cisapride also decreased mean small intestinal transit time of cellulose fiber [2.11 (0.80-5.08) hr vs 2.82 (0.78 7.12) hr; P less than 0.05] and plastic particles [2.06 (1.13-5.13) hr vs 2.64 (1.18-7.04) hr; P less than 0.05]. However, cisapride increased mean large intestinal transit time of plastic particles [31 (13-75) hr vs 23 (12-36) hr; P less than 0.05]. In conclusion, oral cisapride 10 mg four times a day accelerates gastric emptying and small intestinal transit whereas this dose of cisapride seems to delay large intestinal transit of solids in healthy humans. PMID- 2253537 TI - Long-term effects of jejunoileal autotransplantation on myoelectrical activity in canine small intestine. AB - We studied the longitudinal effects of autotransplantation on the motor function of the jejunoileum. By performing the autotransplantation procedure in a manner similar to that employed for allotransplantation, we sought to examine the long term effects of both extrinsic denervation and the operative procedure itself on small intestinal motor function. Although initially disrupted, interdigestive myoelectrical activity demonstrated progressive organization: 88% of migrating myoelectrical complexes in animals studied between 12 and 20 months following autotransplantation demonstrated each phase of the complex in normal sequence. Longitudinal studies of several parameters of myoelectrical activity provided further evidence of progressive organization and entrainment of motor functions within the denervated intestine. Several abnormal myoelectrical patterns were observed within the autotransplanted segment, however, and coordination of either slow wave or phase III activity with the proximal innervated intestine did not recover with time. The major component of the myoelectrical response to feeding was permanently impaired with a delayed onset and shortened duration of the fed response. We conclude that the extrinsically denervated intestine recovers the ability to generate and organize all phases of the MMC but demonstrates permanent impairment of the major motor response to food. However, anoxic and cooling damage to enteric nerves and muscle, incurred during the autotransplantation procedure, may explain the persistence of abnormal motor patterns and impaired myoelectrical conduction and could play an important role, additional to that of extrinsic denervation, in the long-term motor function of the allotransplanted intestine. PMID- 2253538 TI - Primary peritoneal sarcoidosis. AB - A 14-year-old male was admitted for the evaluation of tense exudative ascites. Despite thorough evaluation, the diagnosis remained cryptic until peritoneoscopy revealed diffuse studding of the entire visualized peritoneum with multiple miliary nodules, and peritoneal biopsy demonstrated multiple noncaseating epithelioid granulomas. After other causes were excluded, a diagnosis of sarcoidosis was considered and confirmed with classic endobronchial findings at bronchoscopy. Involvement of the peritoneum with sarcoidosis is rare and, to our knowledge, only one other case describes this as the initial manifestation of this disease. PMID- 2253539 TI - Esophageal adenocarcinoma in a patient with surgically treated achalasia. AB - Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastro-esophageal reflux disease. PMID- 2253540 TI - Development of acute myelocytic leukemia in patients with Crohn's disease. AB - In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases. PMID- 2253541 TI - Massive hepatic infarction in systemic lupus erythematosus. AB - Liver disease in systemic lupus erythematosus, as demonstrated by abnormal histopathology, is rare and usually mild; typically, this hepatic disease is of chronic nature and not related to a hypercoagulable state. A patient is described in whom life-threatening hypercoagulability in association with systemic lupus erythematosus resulted in extensive liver infarction. Follow-up radionuclide liver scintigraphy suggested that regenerative recovery in the infarcted areas of the liver may be delayed or absent, but there was no evident functional hepatic impairment. PMID- 2253542 TI - Closure of refractory perineal Crohn's lesion. Integration of hyperbaric oxygen into case management. AB - A case is reported in which a comprehensive program of hyperbaric oxygen (HBO), surgical debridement and reconstruction, and continuing medical management resulted in complete and sustained closure of an extensive perineal Crohn's lesion refractory to conventional medical and surgical management. It is emphasized that in this case healing occurred in the setting of previous removal of all diseased intestinal tissue and only with the combined use of all three treatment modalities. HBO may be a useful adjunct in the therapy of large nonhealing perineal lesions post-proctocolectomy in patients who are unresponsive to metronidazole or to immunosuppressant therapy or who experience limiting side effects from continued medical therapy. PMID- 2253543 TI - [Kinetics of platelet aggregation]. PMID- 2253544 TI - [Tomato proteins during infection with tomato mosaic virus]. PMID- 2253545 TI - [The effect of peptides-analogs of T4 receptor and HLA class II antigens on the reproduction of human immunodeficiency virus]. PMID- 2253546 TI - [Adhesion receptors--regulators of respiratory burst in neutrophils]. PMID- 2253547 TI - [The effect of cytoplasmic modulator of thyroxine on the activity of RNA polymerase in cell nuclei from rat liver and brain]. PMID- 2253548 TI - [Determination and identification of the nucleoside phosphate in the basal plate of bacteriophage T4]. PMID- 2253549 TI - [Adaptation to stress limits the reperfusion injury of the heart after total ischemia and increases its resistance to the heat shock]. PMID- 2253550 TI - [Selectivity of squirrel visual cortex neurons to the direction of movement of light and dark bands]. PMID- 2253551 TI - [The effect of bathing of newborn rats in ice water on their radioresistance]. PMID- 2253552 TI - [A comparative study of the regenerative capacity of the gastrocnemius muscle in young and old rats with autografts]. PMID- 2253553 TI - [A plasmid vector with cascade regulation of gene expression]. PMID- 2253554 TI - [The functional antagonism of the first and third domains of E. coli SSB proteins in vivo]. PMID- 2253555 TI - The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism. PMID- 2253556 TI - Physiological disposition of HMG-CoA-reductase inhibitors. PMID- 2253557 TI - Cutaneous metabolism of xenobiotics. PMID- 2253558 TI - [Significance of family anamnesis in colorectal carcinoma]. AB - To assess the familial risk of colorectal cancer among first-degree relatives of colorectal cancer patients, a tumour-related family history study was conducted in 1982-1988 on 184 patients (median age 60 [28-92] years). These family data were compared with the data recorded in the cancer register of the population of Basel. An enhanced risk among first-degree relatives was noted (relative risk: 1.8%; 95% confidence interval: 1.4-2.3). The enhanced risk was attributed exclusively to seven families involving 2-3 relatives each (the relative risk in these families being 34). In four of these seven families an autosomal dominant site-specific cancer of the colon (Lynch's syndrome I) was diagnosed. Hence, family case history of colorectal cancer patients enables the identification of relatives with a high risk for colorectal carcinoma. PMID- 2253559 TI - [Long-term results after implantation of autologous cryopreserved parathyroid tissue]. AB - Autologous cryopreserved parathyroid tissue was implanted into 25 patients (12 men and 12 women, median age 45 [24-75] years, and an 18-month-old child) who after a parathyroidectomy for primary or secondary hyperparathyroidism, had developed permanent postoperative hypoparathyroidism. In 12 of the patients it had developed after a second operation for persisting or recurrent hyperparathyroidism. In ten patients it had occurred after total parathyroidectomy and autologous transplantation of fresh parathyroid tissue, in two patients after subtotal parathyroidectomy and in one patient after excision of a solitary parathyroid adenoma following goitre resection. In 22 patients the state of the tissue to be implanted was examined histologically before implantation after defrosting and any necrosis made up by replacement with more than 20 tissue particles. Re-examination took place a median of 40 [3-120] months postoperatively. The high doses of calcium and vitamin D preparations required preoperatively were reduced stepwise in all patients, completely discontinued in 16. At the time of follow-up nine patients were still receiving low doses of calcium and/or vitamin D. Symptoms of hypocalcaemia disappeared in all patients. Thus implantation of autologous cryopreserved parathyroid tissue is a reliable method for the treatment of permanent postoperative hypoparathyroidism. PMID- 2253560 TI - [Primary chondrosarcoma of the ureter]. AB - A 62-year-old patient had complained of recurring colicky pain in the right renal bed, seven days before he was admitted as an inpatient. Macrohaematuria was an accompanying sign during one of these attacks. Sonography revealed right urinary obstruction of medium severity; the right kidney could not be demonstrated by urography. Since CT did not yield any clue, retrograde ureteropyelography was performed. An obstructive tumour of the right ureter was identified. This tumour, which had a length of 3.5 cm and a width of 1.2 cm, was completely resected by ureteronephrectomy. Examination revealed an extraskeletal mesenchymal chondrosarcoma of predominantly intraluminal growth, and a tumour-free external ureteral wall. A chondrosarcoma at this site has not been reported as yet. Pathogenesis may be ascribed either to degeneration of an existing chorista or to the development of a pluripotent tumour parent cell. PMID- 2253561 TI - [Therapeutic possibilities in arthroscopy of the knee joint]. PMID- 2253562 TI - [Nosocomial bacterial pneumonia]. PMID- 2253563 TI - [Serum therapy: discovery of a pioneer therapeutic principle in the year 1890]. PMID- 2253564 TI - [Crohn's disease and Hodgkin's disease]. PMID- 2253565 TI - [Cyanide poisoning]. PMID- 2253566 TI - Appendicitis. PMID- 2253567 TI - Analysis of the pathology of 405 appendices. AB - An analysis was made of 405 appendices removed with the preoperative diagnosis of acute appendicitis. Diagnosis was confirmed histologically in 334 organs. Morphological changes in the appendix were found to correlate with the duration of symptoms. 25% of the acutely inflamed appendices showed significant lymphoid hyperplasia which support the theory that obstruction by lymphoid hyperplasia is important in the pathogenesis of acute appendicitis. Faecoliths, Enterobius vermicularis and schistosomal ova were found in 6.3% and 2.4% of inflamed organs. PMID- 2253568 TI - Implication of altered pulmonary function in pneumonectomy for tuberculous destroyed lung. AB - Twelve patients undergoing pneumonectomy for tuberculous destroyed lung were studied to determine the value of preoperative spirometry in the assessment of their pulmonary reserve, and prediction of their post-operative morbidity. Preoperatively, the functional losses were evidenced by mean values of FVC of 56.4%, FEV1 of 48.9% and PEFR of 65.8%--all expressed as percentage of predicted normals. No significant alteration occurred in pulmonary function post pneumonectomy. All patients were in Class 1 (HYHA) pre- and post-operatively. It is concluded that operability in these patients cannot be based on spirometry alone but must include the preoperative assessment of clinical (symptomatic) stage and cardiovascular status. PMID- 2253570 TI - A type of macular degeneration in adult Nigerians; a possible role of chloroquine. AB - Eleven cases of macular degeneration occurring between the ages of 22 years and 40 years are presented. All the patients gave positive history of chloroquine intake and outdoor activity. In 4 of the 11 cases, pterygium was an associated ocular finding. The female to male ratio was 3 to 1. The macular lesions were bilateral and symmetrical in all the cases. It is postulated that the effect of chronic chloroquine ingestion exacerbated by chronic light toxicity might be responsible for this type of macular degeneration presenting in adults. PMID- 2253569 TI - Constrictive pericarditis in Saudi Arabia. AB - Twenty four patients underwent pericardectomy for constrictive pericarditis. There were 2 operative deaths. Tuberculosis was the aetiological factor in 20 patients and a post surgical aetiology was found in 2 patients. The aetiology remained unclear in 2 patients. PMID- 2253571 TI - A comparison of diprivan and thiopentone when used as induction agents for short surgical procedures. AB - Anaesthetic properties of Diprivan and thiopentone as intravenous induction agents were compared on patients presenting for short surgical or investigative procedures at the Kenyatta National Hospital, Nairobi, Kenya. Each group of the comparative study consisted of 20 cases randomly allocated and similar parameters compared. Diprivan was found to have an overall superiority as an induction agent over thiopentone particularly on recovery characteristics. PMID- 2253572 TI - Multidrug therapy for treatment of paucibacillary leprosy in western Kenya- preliminary communications. AB - A prospective study is being undertaken in Western Kenya to evaluate the effectiveness and tolerability of WHO-MDT, while at the same time comparing it to a modified multidrug regimen, which is rifampicin 1500mg at the onset supervised, and repeated after 3 months and dapsone 100mg daily for 6 months. Preliminary analysis done on 127 cases admitted into the study are presented. The inactivity index observed between 0-12 weeks was 20% for WHO-MDT and 47% for modified-MDT (p less than 0.01). The inactivity index observed between 0-24 weeks was 63.3% for WHO-MDT and 82.3% for modified-MDT (p less than 0.05). The inactivity index observed between 0-32 weeks was 83% for WHO-MDT, and 88% for modified-MDT. Type 1 reaction was noted in 23.3% on those on WHO-MDT, and 20.3% on those cases on modified-MDT (p greater than 0.1). Compliance rate was 93.8% for those on WHO-MDT and 95.2% on those on modified MDT. All regimens were well tolerated. These preliminary results indicate that MDT is effective in treatment of paucibacillary leprosy, and also that clinical cure can be achieved in much shorter duration, particularly with higher dosage of rifampicin. PMID- 2253573 TI - A community based longitudinal study of viral hepatitis B in a rural community. AB - Community based longitudinal epidemiological study of hepatitis B virus (HBV) was done in Maragua between June 1986 and November 1987. Hepatitis B surface antigen (HBsAg) carrier rate in the community was 3%. The high risk groups of HBV infection in the community were members of HBV carrier families and babies born to highly infectious mothers. Horizontal transmission of HBV at school did not seem to be very important. PMID- 2253575 TI - Cholelithiasis in the Kenyan African. AB - A prospective and retrospective review of 20 cases of cholelithiasis diagnosed at Kenyatta National Hospital (KNH) between June 1987 and June 1989 was done. Females were more often affected (6 times) than their male counterparts. 94% of the females were parous with a mean parity of 5.6. Most patients were in the 4th decade at the time of diagnosis. Qualitative analysis for gall-stones showed evidence of cholesterol in all stones analysed with calcium being detected in only one female patient. PMID- 2253574 TI - Serosurvey of prevalence of human immunodeficiency virus amongst high risk groups in Port Sudan, Sudan. AB - During October, 1987, 593 sera were collected from risk groups in Sudan's only major deepwater port, Port Sudan. The risk groups included prostitutes, lorry drivers and prisoners. A large proportion of the study participants practised high risk behaviour which included sexual promiscuity, medical treatment by injection, scarification and tattooing. Despite high risk behaviour and evidence of a high prevalence of hepatitis B infection, a virus transmitted in a manner similar to HIV, no study participants were positive for HIV infection. This data suggests that the prevalence of HIV infection amongst high risk groups in Port Sudan is very low. These findings confirm a lack of clinical cases of AIDS in hospitalized patients in Port Sudan and the small number of reported cases in other areas of northern Sudan. PMID- 2253576 TI - Effects of steroidal contraceptives on gallbladder: a review. AB - In regard to gallbladder disease and oral contraceptive use, more than ten controlled epidemiologic studies have been reported and reviewed in this paper. The findings presented concerning the association of oral contraceptive use with the development of a gallbladder disease are contradictory. Oral contraceptive use and use of estrogens in postmenopausal women have been reported to be associated with increased attack-rates of a gallbladder disease, but the increased risk is found higher in those using estrogens than progestin based oral contraceptives. Other studies, however, have reported little overall effect of oral contraceptive use on the risk of the gallbladder disease. Where increased risk has been documented, this has been more related to duration than overall. The increased risk of oral contraceptive use to gallbladder disease has been observed higher in the 6-12 months of usage. Only one study has reported increased risk of gallbladder disease in long-term users. The increased gallbladder disease in oral contraceptive users may be greater in multiparae than in nulliparae; pregnancy and obesity may also pose an increased risk to the disease in oral contraceptive users. However, these findings are not widely accepted. PMID- 2253577 TI - Chediak-Higashi syndrome: a case report on an African infant. AB - An African Kenyan female infant was born with very light skin and ashen grey, scanty hair. At 18 months she presented with a bluish skin pigmentation, hepatosplenomegaly, generalised lymphadenopathy and non-responsive fever. A bone marrow aspirate and peripheral blood examination done revealed characteristic features of the Chediak-Higashi Syndrome. This is a rare disorder, to our knowledge not previously described in Africans. The case is presented with a brief review of the literature. PMID- 2253578 TI - Qualitative changes of spontaneous movements in fetus and preterm infant are a marker of neurological dysfunction. PMID- 2253579 TI - Preterm and early postterm motor behaviour in low-risk premature infants. AB - The development of spontaneous motility and posture was studied longitudinally in 14 carefully selected low-risk preterm infants. The aim of this investigation was to provide a set of data suitable for comparison with fetuses and with neurologically abnormal preterm infants. The infants were videorecorded weekly, for one hour in a supine position, from birth until their discharge from the hospital. Ten of them were thereafter also observed at home at 3-week intervals from 3 to 18 weeks of corrected age, together with 10 healthy fullterm infants. Occurrence and duration of motor patterns and postures in periods of rest and activity were obtained by off-line analysis of the videotapes. Few significant changes were found from birth until term age in the composition and quantity of the spontaneous movement patterns. Only twitches and stretches during activity periods showed a small decline approaching term age. However, notable inter individual differences and intra-individual fluctuations from week to week were observed. Postterm development of preterm infants was similar to that of the fullterms. Both showed considerable changes in the qualities of general movements after the first postterm weeks. Only fidgety character movements occur earlier in preterm infants. No age-specific preference postures of the limbs were found in the preterm period. Midline position of the head in supine was observed at about the same postterm age in preterm and fullterm groups. Asymmetrical tonic neck postures were very inconsistently present before term age and rapidly disappeared after term, earlier so in preterm infants. PMID- 2253580 TI - Qualitative changes of general movements in preterm infants with brain lesions. AB - The aims of the study were (1) to replicate previous quantitative studies of motor activity in low-risk and high-risk preterm infants and (2) to apply a new method of systematic analysis of the qualitative characteristics of general movements in these two groups of infants. Sequential one-hour videorecordings of the unstimulated infants in the incubator were made during the preterm period and then continued during the postterm period until about 20 weeks. The high-risk group consisted only of infants with signs of haemorrhage and/or leucomalacia in the repeated ultrasonograms of the brain. The neurological follow-up continued up to a minimum of one and a maximum of three years of corrected age. The quantification of the various motor patterns in 12 matched pairs of low-risk and high-risk preterm infants revealed a slight but significant (P = 0.05) excess of isolated arm movements in the low-risk cases during the activity phase. No other movement pattern differed significantly. The qualitative assessment of general movements during the preterm period resulted in all but one of the 14 low-risk cases having a normal quality of general movements. In the lesion-group (N = 29) all the infants had an abnormal quality during the preterm period. Eight cases later became neurologically normal although 1 of them had strabism. In addition, one infant was blind (ROP) and retarded and one other had mental retardation. Nineteen infants later developed cerebral palsy (two monoplegia of a leg, three hemiplegia, 5 diplegia and 9 quadriplegia). Strabism was present in 48.3% of the whole group of 29 cases. A semi-quantitative estimation of various aspects of the abnormal general movements made a typology of abnormal patterns possible. A graphic display of developmental trajectories of individual cases, depicting the course of abnormal aspects along the time axis, helps document the evolution of abnormal signs. Their course is a better predictor of the neurological outcome than the nature and localization of the lesion, detected by imaging techniques. The qualitative assessment of general movements from videorecordings is a reliable, quick, cheap and totally non-intrusive method in neonatology for the early detection of functional impairment of the nervous system. PMID- 2253581 TI - Does reduction of amniotic fluid affect fetal movements? AB - The effect of the amount of amniotic fluid on the form of fetal general movements was studied longitudinally in 19 pregnancies complicated by premature rupture of the amniotic membranes (PROM). Before birth, general movements were studied weekly by means of 1-h ultrasound observations, performed under standardized conditions. In the early postnatal period, 11 of these infants were followed with video recordings of their spontaneous movements. In the fetus, speed and amplitude of general movements were directly related to the reduction in amniotic fluid. A moderate reduction of amniotic fluid was associated with a decrease in amplitude, while a more severe reduction of amniotic fluid caused a decrease in speed as well. Postnatally, the small amplitude and low speed showed a marked tendency to normalize between 1 and 5 weeks. These results are important for the qualitative assessment of motor behaviour in pregnancies with obstetrical complications that are associated with oligohydramnios (such as PROM or intra uterine growth retardation). PMID- 2253582 TI - Acute decrease in vitellogenin synthesis by deprivation of food and water in laying hens. AB - Vitellogenin synthesis during a decrease in egg production caused by depriving food and water was investigated in Single Comb White Leghorn hens. They were transferred from long days of 14L: 10D to short days of 10L: 14D 5 days before food and water deprivation. Then food was deprived for 5 days and water for 2 days. The body weight was markedly decreased by the treatment and reached its minimum after 5 days. The egg production rate which was 85% before the treatment was nil after 4 days. On day 3 the circulating vitellogenin concentrations, measured by a newly established RIA system, was markedly decreased by deprivation of food and water to 22% of the pretreatment level. The concentrations remained less than 10% during cessation of egg laying. Serum luteinizing hormone (LH) and progesterone concentrations decreased gradually, but estradiol 17 beta (E2) decreased abruptly. This acute decrease closely coincided with the decrease in egg production and the weight of the oviduct and ovary. These concentrations were gradually increased after day 16 and returned to the normal level after 46 days. Circulating thyroxine (T4) and triiodothyronine (T3) concentrations gradually increased from the beginning of the change in the day length and peaked on day 7 or 9, whereas reverse (r)T3 rapidly increased. The concentrations again decreased at the beginning of molting which occurred later due to the deprivation of food and water. Thus, these results demonstrated for the first time that the decrease in egg production induced by deprivation of food and water closely related to the decrease in vitellogenin synthesis as well as gonadal and pituitary functions. Further, recovery of egg production was coupled with the increase in the ovary and oviduct weight, and circulating LH, E2, progesterone, and vitellogenin. PMID- 2253583 TI - Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. AB - We investigated the pharmacokinetics of prednisolone (PSL) in six healthy men, with or without glycyrrhizin (GL), to confirm whether GL influences the metabolism of PSL in humans. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS, equivalent to 0.075 mg/kg of PSL), with or without 200 mg of GL. Blood samples were taken from a peripheral vein at 5, 10, 15, 30 and 45 min, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after PSL-HS infusion. The concentration of total PSL in the plasma was analyzed by high-performance liquid chromatography, and the free PSL was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of PSL were determined, using noncompartmental analysis. GL was found to increase significantly the concentration of total PSL at 6, 8 h, and of free PSL at 4, 6, and 8 h after PSL-HS infusion. GL was also found to modify the pharmacokinetics of PSL. After the administration of GL, the area under the curve (AUC) increased, total plasma clearance (CL) decreased, and the mean residence time (MRT) was prolonged. However, only those of AUC, CL, and MRT of free PSL were significantly different. The volume of distribution at a steady-state (Vdss) of both total and free PSL showed no evident change. This suggests that GL increases the plasma PSL concentrations by inhibiting the metabolism of PSL and that it potentiates pharmacological effects of PSL. PMID- 2253584 TI - Similarity and dissimilarity between clinical and laboratory findings, especially anti-thyrotropin receptor antibody in ophthalmic Graves' disease without persistent hyperthyroidism and hyperthyroid Graves' disease. AB - The aim of this study was to investigate thyroid states, significance of anti-TSH receptor antibodies and the clinical courses of patients with euthyroid Graves' ophthalmopathy. The clinical and laboratory finding of 30 patients with euthyroid Graves' ophthalmopathy were briefly as follows: 1) normal sized thyroid or small goiter; 2) negative or weakly positive thyrotropin binding inhibitor immunoglobulin (TBII); 3) normal thyroid [99 m-Tc] pertechnetate uptake; and 4) frequent observations of low serum TSH values. Besides TBII, thyroid stimulating antibody (TSAb) was measured under low salt and isotonic conditions using FRTL-5 rat thyroid cells. Both TBII and TSAb titers were lower in euthyroid Graves' ophthalmopathy than in hyperthyroid Graves' disease. Serum TSH levels frequently became low in patients considered as euthyroid upon the first examination as well as in Graves' patients in remission, reflecting preceding or mild hyperthyroidism. In follow-up studies, these patients with mildly elevated thyroid hormone levels and low TSH levels seldom reached a state of persistent hyperthyroidism, when TBII was negative or only weakly positive. PMID- 2253585 TI - Replacement of L-T4 suppository in MMI treated rabbits. AB - L-T4 suppositories containing 50, 100 or 200 micrograms of L-T4 were given to rabbits treated with MMI. The serum T4 gradually increased within 3.5 and 6.5 hours following the use of 100 and 200 micrograms of L-T4 suppositories, respectively, without an acute increase in serum T3. The increase in serum T4 continued up to 48 hours. The area under the curve (AUC) for serum T4 was evidently dose-dependent. It is concluded from these results that the T4 suppository will be useful as a replacement therapy for patients with hypothyroidism. PMID- 2253586 TI - Effect of EGF administration on EGF receptor mRNA in hCG producing tumor. AB - In this study we examined the expression of EGF receptor mRNA after EGF administration in hCG producing tumor (choriocarcinoma). We transplanted the tissue of choriocarcinoma into female nude mice and investigated the effects of EGF on the growth of tumors, the binding activity of EGF receptor and the expression of EGF receptor mRNA in the tumor tissues. Two doses of EGF 5.0 micrograms, 50 micrograms and phosphate buffered saline as a control were injected subcutaneously every day for four weeks. Removed tumors were used for immunocytochemical studies and EGF receptor mRNA investigations. HCG and EGF receptors were detected immunocytochemically in the tumor. The low dose EGF employed stimulated the tumor growth while the high dose EGF inhibited the tumor growth compared with that of the control group. The binding activity of EGF receptor and the expression of EGF receptor mRNA also changed in accordance with the stimulation or inhibition of tumor growth. The growth of hCG producing tumor by EGF administration appeared to be dependent upon the binding activity of EGF receptor and the expression of EGF receptor mRNA. PMID- 2253587 TI - Transient hypothyroidism in infants born to mothers with chronic thyroiditis--a nationwide study of twenty-three cases. The Transient Hypothyroidism Study Group. AB - To define the difference in prognosis and the clinical features of transient neonatal hypothyroidism in infants born to mothers with chronic thyroiditis, we conducted a nationwide study of this condition. Sixteen mothers with chronic thyroiditis and twenty-three of their offspring with transient hypothyroidism were registered and reported in this paper. Five (group A) of twenty-two live infants showed physical, mental and/or psychomotor developmental delay (IQ below 80). No significant difference between TSH-binding inhibitor immunoglobulin (TBII) or thyroid-stimulation blocking antibody (TSBAb) activities in groups A and B (normal development) were noted. Moreover, there was no significant difference in thyroid function in the newborn period, ages at the start of thyroid medication or the dose and duration of treatment in the two groups. A striking difference observed between the two groups was the thyroid function of their mothers during pregnancy. In group A, four mothers were hypothyroid during pregnancy, and another mother discontinued thyroid medication in the last trimester and her baby was most delayed at the start thyroid medication. On the other hand, the mothers of only two of seventeen live cases in group B had mild hypothyroidism during pregnancy. There were two sets of siblings whose mother received inadequate treatment during the first pregnancy and adequate treatment during the second pregnancy. The psychomotor, physical and mental developmental delay were observed in their first babies. These findings suggested that maternal thyroid function during pregnancy might be an important factor in the prognosis of infants born to mothers with chronic thyroiditis. PMID- 2253588 TI - Vasopressin-induced increases in cellular free calcium concentration measured in single cells of rat renal papillary collecting tubule. AB - We determined the cellular free calcium concentration [Ca2+]i in response to arginine vasopressin (AVP) using single cells of cultured rat renal papillary collecting tubule cells. AVP at a concentration of 1 x 10(-10) M or higher significantly increased [Ca2+]i in a dose-dependent manner. The prompt increase in [Ca2+]i induced by AVP was completely blocked by the V1V2 antagonist, but not by the V1 antagonist. Also, an antidiuretic agonist of 1-deamino-8-D-arginine vasopressin (dDAVP) increased [Ca2+]i, which was blocked by the pretreatment with the V1 V2 antagonist. An AVP-induced increase in [Ca2+]i was still demonstrable in cells pretreated with Ca2(+)-free medium containing 1 x 10(-3) M EGTA, or a blocker of cellular Ca2+ uptake, 5 x 10(-5) M verapamil. These results indicate that AVP increases [Ca2+]i through the V2 receptor in renal papillary collecting tubule cells where cAMP is a well-known second messenger for AVP, and that cellular free Ca2+ mobilization depends on both the intracellular and extracellular Ca2+. PMID- 2253589 TI - Can the type of variant albumin in familial dysalbuminemic hyperthyroxinemia be determined by measuring iodothyronines in serum? AB - A recent report documented the existence of three putative types of variant albumin in dysalbuminemic hyperthyroxinemia (DH) and suggested that measurement of the total concentration of three iodothyronines (T4, T3 and rT3) in serum of affected subjects could aid in their differentiation. In the present report, we describe three affected subjects from a single family which DH exhibited, in addition to increased serum total T4 levels, variable changes in the concentrations of total T3 and rT3. The concentrations of the following iodothyronines were above the normal limit: T4, T3 and rT3 in the propositus, T4 and T3 but not rT3 in her sister, and T4 but not T3 and rT3 in her mother. These differences cannot be caused by structurally different types of variant albumins, because the three subjects are members of the same family. They rather correlated with the relative abundance of the variant albumin in serum of the affected family members. Although previously reported subjects with DH always had serum T4 levels above the normal limit due to the predominantly higher affinity of the variant albumin for T4, significant increases in the concentration of serum T3 and rT3, reaching at times values above the upper normal range, have also been observed. Since a number of factors, including the relative abundance of the variant albumin, influence the concentration of iodothyronines in serum, their measurement alone cannot be used to determine the inherited type of DH. PMID- 2253590 TI - Transient subclinical hypothyroidism in early pregnancy. AB - In the present study, a new clinical state of transient subclinical hypothyroidism in 12 early pregnant women is documented. The incidence of transient subclinical hypothyroidism was 18 (0.19%) among 9,453 pregnant women examined in this series in Sapporo. The characteristics of transient subclinical early gestational hypothyroidism in our study may be summarized as follows: temporarily increased TSH in the blood (11.7 +/- 6.3 microU/ml; mean +/- S.D.) in early pregnant women at 8.5 +/- 2.4 weeks of gestation, accompanied with or without reduced FT4 which spontaneously return to normal at 17.9 +/- 7.1 weeks; no subjective complaints and no previous history of thyroid disease; small struma; positive titers of antimicrosome antibody and antithyroglobulin antibody; normal serum hCG; negative results for TSH receptor antibody. None of the infants show any physical abnormality such as struma and none of the patients had neck pain or fever suggesting subacute thyroiditis. The presence of autoantibody to the thyroid gland and echographical findings strongly suggest the existence of Hashimoto's thyroiditis in early pregnant women with transient subclinical hypothyroidism, although the cause of transient subclinical early gestational hypothyroidism remains obscure. PMID- 2253591 TI - Prolactin does not mediate the suppressive effect of the suckling stimulus on luteinizing hormone secretion in ovariectomized lactating rats. AB - The plasma LH concentration in ovariectomized lactating rats is low for 14 days postpartum, while the prolactin concentration is high during this period. We examined the effect of the inhibition of increased prolactin secretion with bromocriptine (CB-154) on the LH secretion in lactating rats ovariectomized on day 2 (day 0 = day of parturition). Blood samples were collected through an indwelling atrial cannula every day. LH levels were kept low until day 9 in lactating rats injected daily with CB-154 (0.6 mg/day, s.c.). The duration of the period during which LH secretion was suppressed was shorter in lactating rats treated with CB-154 than in saline-injected controls. The replacement with ovine prolactin by means of a mini-osmotic pump (0.3 mg/day, s.c.) in CB-154-treated lactating rats restored the duration of LH suppression. In rats deprived of their pups on day 2, the LH concentration rose immediately after removal of the pups and the LH level was not significantly different between rats treated with CB 154, ovine prolactin and saline, indicating that neither the CB-154 treatment nor the high level of prolactin alone has any effect on LH secretion in rats deprived of their pups. The present results clearly demonstrate that prolactin does not mediate the suppressing effect of the suckling stimulus on LH secretion in early lactation and support our theory that the suckling stimulus controls the LH and prolactin secretion independently at the hypothalamic level. PMID- 2253592 TI - Enhanced ketone body uptake by perfused skeletal muscle in trained rats. AB - Training effect on exercise-induced hyperketonemia was investigated in normal post-absorptive rats subjected to running exercise on a treadmill. Furthermore, rat hindlimb-muscle perfusion was performed to elucidate the mechanism of the training effect. A medium intensity prolonged exercise (running at 15 m/min for 90 min) caused a greater increase in plasma 3-hydroxybutyrate than in acetoacetate both during and after the exercise. Training with medium-intensity exercise (15 m/min) for 90 min 3 times per week for 14 wks or 28 wks caused 1) a reduction of the increase in plasma ketone body (mainly 3-hydroxybutyrate), free fatty acids and glucagon induced by the exercise, and 2) an increase in ketone body (mainly acetoacetate) uptake by perfused skeletal muscle. The present study demonstrates that the reduction of exercise-induced hyperketonemia by prolonged training is caused by increased ketone body utilization in skeletal muscle, and suggested that inhibition of hepatic ketogenesis might also participate in this reduction. PMID- 2253593 TI - Epidermal growth factor receptor mRNA in livers from newborn, adult and partially hepatectomized rats. AB - Epidermal growth factor (EGF) receptor mRNA expression in livers of newborn, adult control and partially hepatectomized rats 1 and 3 days post-operation was examined by Northern blot analysis. A human EGF receptor cDNA (P 64-1, Ullrich et al., 1984) was hybridized to RNA species of 10, 6 and 3 kb. These mRNAs were profoundly decreased in livers from newborn rats and relatively decreased in regenerating rat livers. beta-Actin mRNA in these tissues showed a tendency to increase over that of the adult controls. PMID- 2253594 TI - The release of hepatic triglyceride lipase from rat monolayered hepatocytes in primary culture. AB - The release of hepatic triglyceride lipase from cultured rat hepatocytes and its hormonal regulation were studied. The activity of lipase released into the medium in the presence of heparin was increasing for 24 hours on the 2nd day of culture. The activity in the absence of heparin was only 10% of that in the presence of heparin. When hepatocytes were cultured with anti-hepatic triglyceride lipase IgG, the lipase activity was suppressed by 92%. The results suggest that the enzyme released into the culture medium is identical to hepatic triglyceride lipase which can be released only in the presence of heparin, the mode of release being similar to that of lipoprotein lipase from adipocytes. The addition of colchicine and monensin to the medium resulted in the inhibition of lipase secretion by 20% and 61%, respectively. Insulin enhanced lipase activity only 20%, whereas dexamethasone suppressed the activity by 44%. These data indicated that hepatic triglyceride lipase is secreted and released from hepatocytes in the presence of heparin and its secretion is regulated by hormones. PMID- 2253595 TI - Studies on the T3 suppression test with reference to the thyroidal 123I uptake in Graves' disease: comparison of 24-hour and 3-hour uptake. AB - Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T3 suppression test. The 3-hour and 24-hour thyroidal 123I uptake after T3 administration (75 micrograms/day, 2 weeks) were measured (post T3 uptake). In 38 patients whose post T3 uptake was below 35% in post T3 24-hour uptake, treatment was stopped. The T3 suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of 123I after T3 administration (r = 0.847, p less than 0.001). In 38 patients who showed positive T3 suppression, most patients with MMI withdrawal produced a marked overshoot of post T3 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3 hour uptake values are able to be substituted for 24-hour uptake values during a T3 suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values. PMID- 2253596 TI - Characterization of estrogen receptor in estrogen-dependent transplantable rat pituitary tumor MtT/F84. AB - Properties of nuclear and cytosolic estrogen receptors (ERs) were examined in a new transplantable rat pituitary tumor designated as MtT/F84, of which growth is stimulated by estrogen. The optimal incubation conditions of both nuclear and cytosolic exchange were found to be at 37 degrees C for 15 min and at 25 degrees C for 2 hr, respectively. Molybdate increased a specific binding of estradiol (E2) as determined by [3H]E2-binding assay. Sucrose density gradient analyses of crude cytosol revealed specific peaks of radioactivity in both 4-5S and 8-10S areas. However, only a single 5S peak was present in 0.4M KCl-extractable nuclear ER. Molybdate also enhanced the stability of cytosolic 8-10S receptor in density gradient sedimentation behavior. Scatchard plot analysis for nuclear ER yielded a single class of binding sites with a dissociation constant (Kd) of 0.317 nM and the maximum number of binding sites (NBSmax) of 25.4 fmol/mg protein. Saturation analysis of [3H]estrogen binding to cytosolic ER also yielded a straight line with a Kd of 0.146 nM and NBSmax of 58.5 fmol/mg protein. The effect of E2 administration on the intracellular distribution of ER was also examined. A marked disappearance in the ER binding in cytosol with a concomitant increase in binding in nuclear fraction was found after the administration of the unlabeled E2 in vivo, whereas the total number of ER did not change. Thus, it is concluded that properties of ER in the MtT/F84 were very similar to those in other target organs such as uterus and pituitary gland. PMID- 2253597 TI - Regulatory effects of epidermal growth factor and retinol on the glucocorticoid receptor level in cultured chick embryonic skin. AB - When undifferentiated skin from 13-day-old chick embryos was cultured in a chemically defined medium, glucocorticoid specifically decreased the dexamethasone-binding activity of the epidermal cytosol after 1 day of culture, 3 days before it induced formation of a cornified layer over the intermediate cells of the epidermis. The binding activity reappeared after removal of the steroid from the medium. This reappearance was inhibited by epidermal growth factor (EGF, 100 ng/ml). The Addition of 2 microM retinol resulted in a 3-fold increase in specific dexamethasone binding in the epidermal cytosol within 12 h with no change in the binding affinity. The inhibition of glucocorticoid-induced keratinization by retinol is due a to mechanism other than inactivation of the glucocorticoid receptor. PMID- 2253598 TI - Dynamics of sulfur dioxide absorption in excised porcine tracheae. AB - The absorption of sulfur dioxide (SO2) into excised porcine tracheae was characterized by a step-response experiment in which SO2 outlet concentration was monitored during the 30-min interval following introduction of inlet concentrations of 0.1-0.6 ppm at steady air flows of 2.7-11.0 liter/min. These data were analyzed with a diffusion-reaction theory incorporating three independent parameters--a gas phase mass transfer coefficient, kg, a tissue phase diffusivity x solubility product, D(alpha RT)2, and a tissue phase reaction constant, kr. While single values of 17 sec-1 for kr and 0.28 m2/sec for D(alpha RT)2 were sufficient to simulate all the data, it was necessary to vary kg from a 0.032 to 0.121 m/sec in direct proportion to the gas flow. Based on these parameter values, gas phase resistance accounts for about one-fourth of the total resistance to absorption in gas and tissue phases combined. All three parameters were independent of inlet concentration, implying that diffusion, solubility, and irreversible reaction of SO2 in tissue are all linear processes. PMID- 2253599 TI - Inhibition of liver, kidney, and erythrocyte delta-aminolevulinic acid dehydratase (porphobilinogen synthase) by gallium in the rat. AB - Selective inhibition of enzymes in the heme biosynthesis pathway with concomitant urinary excretion of heme precursors serve as potentially important biological markers of chemical exposure and cell injury. Intratracheal administration of gallium arsenide particulate suspensions has been shown to result in inhibition of delta-aminolevulinic acid dehydratase (ALAD) in several tissues and increased excretion of the heme precursor aminolevulinic acid (ALA). This study was undertaken to evaluate in vivo the role of gallium alone in ALAD inhibition and increased urinary excretion of ALA. Male CD rats received a single ip injection of Ga2(SO4)3 at doses of 12.5, 25, 50, 100, and 200 mg Ga/kg. A dose-dependent inhibition of ALAD was observed 24 hr later in liver, kidney, and erythrocytes. After injection of 25 mg Ga/kg, maximal inhibition (42 to 49% of control) of ALAD occurred between 6 and 24 hr in liver and kidney with full recovery of activity at 96 hr. In erythrocytes, maximal inhibition (48% of control) occurred between 24 and 48 hr with recovery of activity at 96 hr. Mild to moderate renal proximal tubular necrosis in the pars recta was observed 24 hr after administration of 100 and 200 mg/kg, but no histopathologic changes were evident at lower doses. No consistent changes in urinary excretion of ALA were observed. Lineweaver-Burk analyses of renal and hepatic ALAD activities in the absence and presence of gallium indicated that the inhibition of ALAD by this element is noncompetitive (same Km, decreased Vmax). Gallium was shown to possess an inhibition constant (Ki) of approximately 3 microns for ALAD, similar to the Ki obtained for lead in other studies. Incubation of ALAD in vitro with gallium and lead, an active thiol group inhibitor, resulted in a greater inhibition of the enzyme. Further in vitro studies demonstrated the attenuation of gallium inhibition of hepatic and renal ALAD by zinc, suggesting that the mechanism of gallium action may involve competition for or displacement of zinc from the sulfhydryl group of the enzyme active site. Since ALAD inhibition occurred at doses at which no histopathologic changes were evident, the determination of ALAD activity in various tissues, including blood, may be of potential value as a biomarker of exposure/toxicity to metals such as gallium. The effect of chemical form and route of exposure of gallium and effects of other Group III metals on inhibition of ALAD and excretion of ALA is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253600 TI - A test of the linear-no threshold theory of radiation carcinogenesis. AB - It has been pointed out that, while an ecological study cannot determine whether radon causes lung cancer, it can test the validity of a linear-no threshold relationship between them. The linear-no threshold theory predicts a substantial positive correlation between the average radon exposure in various counties and their lung cancer mortality rates. Data on living areas of houses in 411 counties from all parts of the United States exhibit, rather, a substantial negative correlation with the slopes of the lines of regression differing from zero by 10 and 7 standard deviations for males and females, respectively, and from the positive slope predicted by the theory by at least 16 and 12 standard deviations. When the data are segmented into 23 groups of states or into 7 regions of the country, the predominantly negative slopes and correlations persist, applying to 18 of the 23 state groups and 6 of the 7 regions. Five state-sponsored studies are analyzed, and four of these give a strong negative slope (the other gives a weak positive slope, in agreement with our data for that state). A strong negative slope is also obtained in our data on basements in 253 counties. A random selection-no charge study of 39 high and low lung cancer counties (+4 low population states) gives a much stronger negative correlation. When nine potential confounding factors are included in a multiple linear regression analysis, the discrepancy with theory is reduced only to 12 and 8.5 standard deviations for males and females, respectively. When the data are segmented into four groups by population, the multiple regression vs radon level gives a strong negative slope for each of the four groups. Other considerations are introduced to reduce the discrepancy, but it remains very substantial. Since cigarette sales data are available only on a statewide basis, mean radon data for states are analyzed. The linear regression for lung cancer rates vs radon levels is also negative and has a much steeper slope than that for the county data. When cigarette sales per capita is introduced into the regression, the negative slope for dependence on radon level is essentially unchanged. PMID- 2253601 TI - Benzene: environmental partitioning and human exposure. AB - A multimedia transport model was used to evaluate the environmental partitioning of benzene. Measured and predicted environmental concentrations were used to estimate the accumulation of benzene in the food chain and the subsequent extent of human exposure from inhalation and ingestion. Results show that benzene partitions mainly into air (99.9%) and that inhalation is the dominant pathway of human exposure, accounting for more than 99% of the total daily intake of benzene. Ingestion of contaminated food items represents only a minor pathway of human exposure. The long-term average daily intake of benzene by the general population of the U.S. was estimated using three independent methods. Intake estimates based on measured personal air exposures, measured exhaled air concentrations, and a pharmacokinetically derived adipose tissue concentration (73, 63, and 72 micrograms/day, respectively) are in good agreement. Although inhalation is the primary route of human exposure to background levels of benzene in the environment, smoking was found to be the largest anthropogenic source of background human exposure to benzene. PMID- 2253602 TI - Metabolism and bacterial mutagenicity of binary mixtures of benzo(a)pyrene and polychlorinated aromatic hydrocarbons. AB - The results of both the Salmonella/microsome mutagenicity assay and high performance liquid chromatography (HPLC) analysis were used to evaluate the interactions of binary mixtures of benzo(a)pyrene (BAP) and several different polychlorinated aromatic hydrocarbons. Binary mixtures of either 2-nitro-3,7,8 trichlorodibenzo-p-dioxin (2NTCDD) or pentachlorophenol (PCP) with BAP produced synergism, whereas strictly additive effects were observed with mixtures of octa- or hepta-chlorodibenzo-p-dioxin and BAP. At a dose of 50 micrograms per plate, BAP induced 120 total revertants, whereas the binary mixture of BAP and PCP induced 303 total revertants. The binary mixture of BAP at 1 microgram per plate and 2NTCDD at 0.5 microgram per plate induced 261 net revertants, whereas BAP alone induced 42 net revertants. HPLC analysis of the mixtures indicated that preincubation of BAP with 2NTCDD increased the quantity of benzo(a)pyrene-7,8 dihydrodiol, and 9,10-dihydrodiol metabolites detected. The data suggest that nonmutagenic components of a complex mixture may alter the metabolism of promixate mutagens. Thus, in the present study, 2NTCDD appears to have inhibited the detoxication of BAP metabolites. PMID- 2253603 TI - Stability of the mutagenicity in stored cigarette smokers' urine and extract. AB - Urine from cigarette smokers was analyzed for the effect upon mutagenic activity when stored for as long as 175 days. Frozen aliquots of urine were thawed out at various time points in the study and prepared for bioassay. These urine extracts were not bioassayed immediately, but rather refrozen until all of the unprocessed urine samples had eventually been prepared for bioassay. All extracts were obtained using cyanopropyl solid phase extraction techniques. At the end of 175 days, all extracts were bioassayed using a microsuspension assay of Salmonella typhimurium TA98. Urine from smokers was found to be mutagenic (14.4-30.9 revertants/ml equivalent) while a control set of urine from non-smokers was not. Data from the storage study when analyzed by analysis of variance techniques indicated no statistical loss of mutagens occurred over the 175-day period although near significance was observed (P = 0.054). This near significance was the result of decreasing mutant response as storage time increased for two of the higher doses tested. PMID- 2253604 TI - In vitro and in vivo genotoxicity evaluation of hormonal drugs. I. Hydrocortisone. AB - Genotoxic evaluation of a widely used glucocorticoid, hydrocortisone, was undertaken using a battery of in vitro and in vivo test systems. Human lymphocyte cultures and mouse bone marrow studies (micronuclei and sister chromatid exchange analyses) showed the drug to be very potent clastogen. However, the Ames/Salmonella assay both with and without S9 did not show an increase in the His+ revertants. PMID- 2253605 TI - An evaluation of the CHO/HGPRT mutation assay involving suspension cultures and soft agar cloning: results for 33 chemicals. AB - The Chinese hamster ovary cell assay (CHO), which measures forward mutation of the HGPRT locus, is used in several laboratories for the detection of mutagens. A procedure involving treatment of CHO cells in suspension culture and mutant selection in soft agar cloning has been developed (Oberly TJ, Bewsey BJ, Probst GS (1987): Mutat Res 182:99-111). In order to evaluate the effectiveness of these modifications, 33 chemicals representing six chemical classes were tested, and the results were compared to findings obtained in other tests for genotoxicity at Lilly Research Laboratories (LRL). A positive response was obtained with 21 chemicals, all of which are recognized mutagens. Of the 12 compounds that produced negative results, 4 were considered to be mutagens and/or carcinogens. Twelve of the compounds mentioned in this report have been previously tested in the CHO/HGPRT assay by other laboratories, and the results showed strong agreement between laboratories. These findings support the conclusion that the use of suspension cultures and soft agar cloning in the CHO assay provides a sensitive test for the identification of mutagens and is a viable alternative to the traditional monolayer procedure of O'Neill et al. (O'Neill JP, Couch DB, Machanoff R, San Sebastian JR, Brimer PA, Hsie AW (1977): Mutat Res 45:103-109). PMID- 2253606 TI - Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. V: Results with 46 chemicals. AB - Forty-six coded chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary (CHO) cells using a standard protocol with and without exogenous metabolic activation. Sixteen chemicals were negative and 15 were positive in both assays; 15 were positive for SCEs only (one chemical that was positive for SCEs was equivocal for ABs), and no chemicals induced ABs only. The effect of cell harvest time on the ability to detect the induction of ABs was examined for 18 chemicals. Seven chemicals produced a positive response using both standard and extended harvest times, five were positive only using an extended harvest time, and six were negative using both harvest times. The relationship between cell cycle delay and SCE induction was also examined, and the two appear to be unrelated. PMID- 2253607 TI - Morphological transformation of BALB/3T3 cells by various procarcinogens in the presence of a rat liver S-9 activation system. AB - An Aroclor-induced rat hepatic S-9 metabolic activation system was incorporated into the BALB/3T3 cell transformation assay to increase its sensitivity to a wide range of procarcinogens. S-9 was prepared from Aroclor 1254-induced (500 mg/kg) Fischer 344 rats. Cyclophosphamide, dimethylnitrosamine, 2-aminofluorene, and 2 naphthylamine were metabolized to reactive forms capable of inducing both dose dependent toxicity and morphological transformation of BALB/3T3 cells. Treatments without an exogenous metabolic activation system were nontoxic and nontransforming. Adaptation of this commonly used exogenous metabolic activation system to BALB/3T3 cells will allow detection of the transforming potential of procarcinogens which test negative in a standard assay. PMID- 2253608 TI - The feasibility of using Chinese hamsters as an animal model for aneuploidy. AB - The utility of Chinese hamsters as a test species for aneuploidy analysis was studied using four chemicals--vincristine, methyl 2-benzimidazole carbamate (MBC), nocodazole, and cyclophosphamide. Ten or more male Chinese hamsters were used per dose and bone marrow was removed at intervals of 6-96 hr. Slides were coded and 50-100 metaphases were analyzed per animal. A metaphase with more than 22 chromosomes was classified as a hyperploid cell, and the data were evaluated by using a one-tailed Fisher's exact test. In experiments using vincristine, MBC, and nocodazole, the frequencies of hyperploid cells were 0.43, 1.14, and 0.91%, respectively, for the control groups. In the experiment using cyclophosphamide, the control value frequency was 3.75%. The treated groups showed no significant increase in hyperploid frequencies when compared to concurrent controls at each of the treated times, except the value at 24 hr for the group that had been treated with vincristine at 0.75 mg/kg. However, this increase was not significant when compared to the overall value for pooled controls, with or without the cyclophosphamide control. Therefore, no significant effects due to chemical treatment were obtained in the present study. The results illustrate the extent of animal-to-animal as well as experiment-to-experiment variability in hyperploid frequencies and the importance of incorporating concurrent controls in assays for aneuploidy. PMID- 2253609 TI - Are short-term genetic tests useful for predicting carcinogenicity? A panel discussion revisited. PMID- 2253610 TI - Ultimate limits for the reaction flux and metabolite levels that may be evolutionarily reached in a linear metabolic pathway. AB - A relationship is derived for the maximum steady-state reaction rate that may be supported by an enzyme catalysing substrate/product interconversion by a generalized Michaelian mechanism for a single-substrate reaction. This relationship is used to characterize the ultimate kinetic and thermodynamic limits for the evolutionary improvement of a linear metabolic sequence of reactions catalysed by Michaelian enzymes in response to a selective pressure in the direction of increased reaction flux. A mathematical analysis is presented which provides explicit expressions for the maximum reaction flux and metabolite concentrations that can be evolutionarily reached in such a pathway. These expressions may be used to obtain information on the reaction steps that represent ultimate bottlenecks for the attainment of high reaction flux in a certain pathway and to identify the enzymes that ultimately are likely to exert main flux control. PMID- 2253611 TI - What metabolite levels may be evolutionarily reached in the glycolytic pathway? AB - The thermodynamic and kinetic properties of the glycolytic pathway have been analyzed in order to characterize the ultimate limits for the metabolite concentrations that may be evolutionarily reached in response to a selective pressure in the direction of increased glycolytic reaction flux. The results indicate that the chemical potential for conversion of glucose into pyruvate at presently observed levels of these two metabolites (and of NADH, NAD+, ATP, ADP and inorganic phosphate) is high enough to allow ultimately for an accumulation of fructose 1,6-bisphosphate at concentrations which may be considered as indefinitely high from a practical point of view. This means that non-kinetic factors such as metabolite solubility put a definite limit to the glycolytic reaction flux that may be evolutionarily reached. With the reasonable assumption that evolution eventually may raise the concentration of fructose 1,6 bisphosphate minimally to the same level as that presently attained by glucose, analytical evidence is presented to show that catalytic improvement of enzymes in the glycolytic pathway ultimately may result in glycerone phosphate levels that are at least two orders of magnitude higher than those presently observed. This argues strongly against the idea that triose-phosphate isomerase represents a perfectly evolved catalyst in the sense that it should have reached the end of its evolutionary development. PMID- 2253612 TI - Delineation of the minimal portion of the Bacillus sphaericus 1593M toxin required for the expression of larvicidal activity. AB - The two genes of Bacillus sphaericus 1953M coding for the 51.4-kDa and 41.9-kDa proteins are both required for the expression of the active larvicidal toxin in Escherichia coli. The minimal size of the active peptide of the 41.9-kDa toxin was defined by in vitro deletion analysis of the gene and found to consist of 338 amino acids (38.3 kDa). N-terminal deletions past the Ile18 residue and C terminal deletions past the His352 residue result in the loss of toxic activity and rapid degradation of such modified toxins by host proteases. The minimal active 38.3-kDa peptide produced in E. coli seems to mimick the stable processed form of the toxin found in larval midguts. However, it still requires the action of the synergistic 51.4-kDa protein for the larvicidal activity. PMID- 2253613 TI - Physical and immunological characterization of human transcription factor IIIA. AB - Human transcription factor IIIA (htFIIIA), specifically required for transcription of the gene for 5S ribosomal RNA has been characterized with respect to some of its physical, immunological and functional properties. TFIIIA from HeLa cells, which selectively binds 5S RNA, is a monomer of approximately 35 kDa with a Stokes' radius of approximately 2.65 nm and a sedimentation coefficient of approximately 2.8 S. These values indicate that the human protein is of rather globular shape and hence diverges not only in molecular mass but also in most of the molecular properties from its highly asymmetric counterpart in Xenopus laevis oocytes. By raising specific polyclonal antibodies against hTFIIIA it was shown in Western immunoblots that there was no cross-reaction between anti-hTFIIIA antibodies and the amphibian protein. Conversely, monoclonal antibodies against three domains of X. laevis TFIIIA antibodies and the amphibian protein. Conversely, monoclonal antibodies against three domains of X. laevis TFIIIA did not cross-react with the human transcription factor. The polyclonal antisera raised against hTFIIIA specifically neutralized binding of the human transcription factor to 5S DNA and abolished in vitro transcription of 5S RNA but these antibodies were unable to inhibit 5S RNA synthesis in cellular extracts from Xenopus, Drosophila or yeast cells. Finally, the species variation of TFIIIA could be substantiated by electrophoretic mobility shift assays revealing preferential binding of hTFIIIA to the homologous 5S RNA gene. PMID- 2253614 TI - Tertiary structure of two-electron reduced Megasphaera elsdenii flavodoxin and some implications, as determined by two-dimensional 1H-NMR and restrained molecular dynamics. AB - The tertiary structure of the non-crystallizable two-electron-reduced Megasphaera elsdenii flavodoxin (15 kDa, 137 amino acid residues) has been determined using nuclear Overhauser enhancement restraints extracted from two-dimensional 1H-NMR spectra. A tertiary structure satisfying the experimental restraints very well (maximum NOE violation of 66 pm) was obtained with use of restrained molecular dynamics, using 509 distance restraints (including one non-NOE) on a starting structure modeled from the crystal structure of one-electron-reduced Clostridium MP flavodoxin. The protein consists of a central parallel beta-sheet surrounded on both sides by two alpha-helices. The flavin is positioned at the periphery of the molecule. The tertiary structure of the protein is highly defined with the exception of the flavin. The latter is expected to result from performing the restrained molecular dynamics simulation without water molecules and without proper charges on the flavin. The flavin, including the phosphate, the ribityl side chain and the isoalloxazine ring, is solvent accessible under the experimental conditions used and evidenced by a two-dimensional amide exchange experiment. This accessibility is expected to be important in the redox potential regulation of the semiquinone/hydroquinone couple of the protein. The amide exchange against deuterons and several typical line shapes in the two-dimensional NMR spectra are consistent with the structure generated. The structure is discussed in detail. PMID- 2253615 TI - Amino acid sequence of a 12-kDa inhibitor of protein kinase C. AB - The complete primary structure of a bovine-brain-derived inhibitor of protein kinase C has been established. Fragments of the purified protein were obtained by cleavage with cyanogen bromide, Staphylococcus aureus V8 protease, trypsin and chymotrypsin. Subsequent analysis of the resulting fragments by fast-atom bombardment mass spectrometry and Edman degradation revealed a calculated molecular mass of 11,779 Da with the following 107-amino-acid sequence: [sequence: see text] This inhibitor does not share significant primary structural identity with any other known protein. PMID- 2253616 TI - A two-dimensional 1H-NMR study on Megasphaera elsdenii flavodoxin in the oxidized state and some comparisons with the two-electron-reduced state. AB - Assignments for the 137 amino acid residues of oxidized Megasphaera elsdenii flavodoxin have been made using the sequential resonance assignment procedure. Great benefit was experienced from assignments of the fully reduced protein. The secondary and tertiary structures of the typical alpha/beta protein remain virtually identical on going from the oxidized to the two-electron-reduced state as judged from two-dimensional NOE spectroscopy. However, functionally important conformation changes in the flavin-binding region do occur on reduction. Considerable reduction-state-dependent chemical shift variations of protons in the immediate vicinity of the isoalloxazine moiety take place. From analysis of these shifts, it can be concluded that ring current effects of the pyrazine part of the flavin diminish on two-electron reduction. PMID- 2253617 TI - Biosynthesis of the lantibiotic Pep5. Isolation and characterization of a prepeptide containing dehydroamino acids. AB - Pep5 is a tricyclic peptide antibiotic which contains the unusual amino acids dehydrobutyrine, lanthionine and 3-methyllanthionine. It is matured from a 60 amino-acid precursor peptide (pre-Pep5) deduced from the sequence of the structural gene pepA. To study the biosynthesis of Pep5 we tried to isolate the primary translation product. We identified a peptide in crude extracts of the Pep5-producing Staphylococcus epidermidis strain using antibodies raised against a synthetic 26-residue peptide representing the leader peptide region of pre Pep5. The putative precursor was purified by reversed-phase HPLC. The isolated peptide did not react with antibodies directed against a C-terminal fragment of mature Pep5 containing two sulfide bridges. Neither lanthionine nor 3 methyllanthionine was detected in amino acid analysis of the isolated precursor. Its amino acid sequence was identical with the sequence predicted from pepA, but Edman degradation stopped at the first threonine residue of the prolantibiotic region indicating a posttranslational modification at this position. The molecular mass of the isolated peptide was 6575.4 +/- 1.7 Da, determined by ion spray mass spectrometry. This is in agreement with a molecule being dehydrated at the four threonine and the two serine residues in the propeptide region; such a peptide has a calculated molecular mass of 6576.7 Da. The results strongly suggest that maturation of the lantibiotic Pep5 is initiated by selective dehydration of hydroxyamino acids in the propeptide region of the primary translation product and that thioether ring formation is not closely linked to dehydration. PMID- 2253618 TI - ADP-ribosylation of actin isoforms by Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin. AB - The substrate specificities of the actin-ADP-ribosylating toxins, Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin were studied by using five different preparations of actin isoforms: alpha-skeletal muscle actin, alpha cardiac muscle actin, gizzard gamma-smooth muscle actin, spleen beta- and gamma cytoplasmic actin, and aortic smooth muscle actin containing alpha- and gamma smooth muscle actin isoforms. C. perfringens iota toxin ADP-ribosylated all actin isoforms tested, whereas C. botulinum C2 toxin did not modify alpha-skeletal muscle actin or alpha-cardiac muscle actin. Spleen beta/gamma-cytoplasmic actin and gizzard gamma-smooth muscle actin were substrates of C. botulinum C2 toxin. In the aortic smooth muscle actin preparation, gamma-smooth muscle actin but not alpha-smooth muscle actin was ADP-ribosylated by C. botulinum C2 toxin. The data indicate that, in contrast to C. perfringens iota toxin, C. botulinum C2 toxin ADP-ribosylates only beta/gamma-cytoplasmic and gamma-smooth muscle actin and suggest that the N-terminal region of actin isoforms define the substrate specificity for ADP-ribosylation by C. botulinum C2 toxin. PMID- 2253619 TI - Effect of isolated C-terminal fragment of theta-toxin (perfringolysin O) on toxin assembly and membrane lysis. AB - theta-toxin, a thiol-activated cytolysin, binds cholesterol and assembles on plasma membrane during the lytic process. In order to understand the process at the molecular level, two fragments (T1 and T2) were isolated from a nicked toxin obtained by limited proteolysis with trypsin. Although neither the T1 nor T2 fragment has hemolytic activity. T2 has almost the same potential as native theta toxin in its binding affinity for erythrocytes and in its binding specificity for cholesterol. T2, derived from the C-terminus of the toxin, loses binding activity upon 5,5'-dithiobis(2-nitrobenzoic acid) modification of the thiol group. The T2 fragment was found to abolish the hemolytic activity of theta-toxin completely without any inhibition of theta-toxin binding to erythrocytes. theta-toxin normally appears in polymeric form on membranes, while it remains in monomer form in the presence of the T2 fragment, as judged by sedimentation patterns in sucrose density-gradient centrifugation. These results indicate that without inhibiting binding, the T2 fragment inhibits hemolysis by preventing theta-toxin from aggregating on membranes, a step that might be essential for the lytic process. PMID- 2253620 TI - Kinetics of the oxidation of ferrocyanide by lactoperoxidase compound II. AB - The kinetics of the oxidation of ferrocyanide by lactoperoxidase compound II has been studied over the pH range 5.2-9.9 at 25 degrees C and an ionic strength of 0.11 M. For all pH values, exponential decay curves are obtained for the reaction of compound II in the presence of ferrocyanide which yielded pseudo-first-order rate constants kobs. The spontaneous decay of compound II in the absence of ferrocyanide occurs at an appreciable rate which was measured independently and used in the data analysis. At all pH values two striking effects were observed when the rate of the decay reaction in the presence of ferrocyanide, kobs, was plotted against ferrocyanide concentration: a saturation effect and positive intercepts which are attributable to the spontaneous decay. The plots of kobs versus ferrocyanide concentration were analyzed in terms of the following parameters: a first-order rate constant k3,obs, a Michaelis constant Km,obs and a spontaneous-decay rate constant k4. The parameters k3,obs and Km,obs describe the reaction of compound II with ferrocyanide, independently of the spontaneous decay. The parameter k4 has only a small pH dependence, whereas plots of the logs of k3,obs and Km,obs versus pH have slopes of -1 at high pH. The major part of the pH dependence can be explained by the influence of a single heme-linked acid group in the LPO-compound-II-ferrocyanide complex. PMID- 2253621 TI - Photoaffinity labelling of the purine-cytosine permease of Saccharomyces cerevisiae. AB - 8-Azidoadenine was used as a photoaffinity reagent to characterize the purine cytosine permease of Saccharomyces cerevisiae. It is a potent competitive inhibitor of cytosine uptake and irradiation of the cells incubated with the label induced the irreversible inactivation of cytosine uptake. Addition of excess cytosine prevented this labelling which was restricted to the outer face of the plasma membrane since it was not accumulated by the cells. In the strain with the amplified purine-cytosine permease gene the maximum cytosine uptake rate was increased 4-5-fold relative to wild type without a modification of the Michaelis constant of uptake (Kt); no uptake could be measured in the deleted strain. The relative amounts of specific labelling determined for the cells and for membrane preparations were 0, 1 and 4 for the null, the wild-type and the amplified strains, respectively. One major band specifically labelled by [3H]azidoadenine, corresponding to a polypeptide with an apparent molecular mass of 45 kDa, was observed in the wild type, amplified in the strain carrying the multicopy plasmid and not detected in the deleted strain. Therefore this polypeptide corresponds to the purine-cytosine permease. PMID- 2253622 TI - Early events in the import/assembly pathway of an integral thylakoid protein. AB - The light-harvesting chlorophyll a/b protein (LHCP) is nuclear-encoded and must traverse the chloroplast envelope before becoming integrally assembled into thylakoid membranes. Previous studies implicated a soluble stromal form of LHCP in the assembly pathway, but relied upon assays in which the thylakoid insertion step was intentionally impaired [Cline, K., Fulsom, D. R. and Viitanen, P. V. (1989) J. Biol. Chem. 264, 14225-14232]. Here we have developed a rapid-stopping procedure, based upon the use of HgCl2, to analyze early events of the uninhibited assembly process. With this approach, we have found that proper assembly of LHCP into thylakoids lags considerably behind trans-envelope translocation. During the first few minutes of import, two distinct populations of mature-size LHCP accumulate within the chloroplast. One is the aforementioned soluble stromal intermediate, while the other is a partially (or improperly) assembled thylakoid species. Consistent with precursor/product relationships, both species reach peak levels at a time when virtually none of the imported molecules are correctly assembled. These results confirm and extend our previous interpretation, that upon import, preLHCP is rapidly processed to its mature form, giving rise to a soluble stromal intermediate. They further suggest that the stromal intermediate initially inserts into the thylakoid bilayer in a partially assembled form, which eventually becomes properly assembled into the light-harvesting complex. PMID- 2253623 TI - Structural transition of alpha 1-antitrypsin by a peptide sequentially similar to beta-strand s4A. AB - Crystal structure studies have shown that cleaved and intact serpins differ essentially in the topology of beta-sheet A. This is five-stranded in the intact molecules and six-stranded after cleavage by insertion of strand s4A whose C terminus has become free [Lobermann, H., Tokuoka, R., Deisenhofer, J. & Huber, R. (1984) J. Mol. Biol. 177, 531-556; Wright, T. H., Qian, H. X. & Huber, R. (1990) J. Mol. Biol. 213, 513-528]. The structural transition is accompanied by changes in spectral properties and an increase in thermal stability. We show here that an N alpha-acetyl-tetradecapeptide with the amino acid sequence of strand s4A, residues 345-358 of human alpha 1-antitrypsin, associates with intact alpha 1 antitrypsin and forms a stoichiometric complex with properties very similar to cleaved alpha 1-antitrypsin. Complex generation has the characteristics of a folding process. PMID- 2253624 TI - Interaction of hemoglobin with chloride and 2,3-bisphosphoglycerate. A comparative approach. AB - The equilibrium oxygen-binding properties of hemoglobins from reindeer (Rangifer tarandus tarandus), musk ox (Ovibos muschatos) and a bat (Rousettus aegyptiacus) have been investigated with special reference to the effect of heterotrophic ligands such as chloride and 2,3-bisphosphoglycerate [Gri(2,3)P2]. The results obtained with hemoglobins from reindeer and musk ox indicate that their low oxygen affinity and their insensitivity to Gri(2,3)P2 are not only an intrinsic property of the molecule, as proposed in the case of ruminant hemoglobins, but also the results of the interplay between chloride and Gri(2,3)P2 interactions. In other words, insensitivity of reindeer and musk ox hemoglobins to Gri(2,3)P2 is mainly due to a decreased affinity constant for this cofactor and to an increased affinity constant for chloride anions; this renders more effective the competition of chloride for th anion-binding site. On the other hand bat hemoglobin behaves in a completely different way and could be regarded as a type case of low-affinity hemoglobin since its functional properties are modulated neither by chloride nor by Gri(2,3)P2. The results are discussed in the light of the amino acid residues which are known to be involved in the binding of organic phosphates. PMID- 2253625 TI - Amino acid sequence of the monomer subunit of the giant extracellular hemoglobin of the aquatic oligochaete, Tubifex tubifex. AB - The extracellular hemoglobin of the aquatic oligochaete Tubifex tubifex consists of four subunits: a monomer of 16.5 kDa, a disulfide-bonded trimer of about 50 kDa and at least two subunits of about 30 kDa. The complete amino acid sequence of the monomeric subunit was determined: it consists of 141 amino acid residues and has a molecular mass of 16,286 Da including a heme group. 39 residues (28%) were found to be identical with those in the corresponding positions in the monomeric globin chains from Lumbricus terrestris, Pheretima sieboldi, and Tylorrhynchus heterochaetus. Tubifex and Lumbricus are most similar, with 75 amino acid identities (53%). There are eight invariant residues amongst these monomeric globins and the intracellular monomeric globin of Glycera and the human beta-globin. The monomeric globin from Tubifex aligns best with those of group A, globins which have a Cys in their second position and an invariant Lys-Val-Lys at positions 9-11 [Gotoh et al. (1987) Biochem. J. 241, 441-445]. The two cysteine residues, at positions 2 and 131, appear to be disulfide-bonded. PMID- 2253626 TI - Properties of purified squalene-hopene cyclase from Bacillus acidocaldarius. AB - The squalene-hopene cyclase from Bacillus acidocaldarius cytoplasmic membrane, was purified to homogeneity by solubilization with Triton X-100, chromatography on DEAE-cellulose, phenyl Sepharose and two gel-filtration columns. The enzyme monomer had a molecular mass of 75 kDa. The sequence of the first 23 amino acids was determined by Edman degradation. The enzyme activity was efficiently inhibited by n-alkyldimethylammonium halides with alkyl chain lengths between 12 and 18 C atoms. Inhibition was also observed with (5 hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate, dodecyldimethylamine N-oxide, azasqualene and farnesol. Competitive inhibition with dodecyltrimethylammonium bromide, (5-hydroxycarvacryl)trimethylammonium chloride 1-piperidine carboxylate and dodecyldimethylamine N-oxide was demonstrated by Lineweaver-Burk plots. PMID- 2253627 TI - Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation. AB - Protein kinase C is maintained in an inactive state by the action of an inhibitory region within the effector binding domain of the kinase. It has been suggested that a short stretch of amino acids (pseudosubstrate site) mediates this inhibition by binding to the active site and preventing substrate interaction [House, C. and Kemp, B. E. (1987) Science 238, 1726-1728]. A mutated version of protein kinase C-alpha containing a glutamic acid for alanine substitution in this region has been analysed for biochemical properties and biological function. Consistent with the importance of this pseudosubstrate site in regulating kinase activity, this altered protein has a significantly increased effector-independent kinase activity relative to wild-type protein kinase C-alpha and shows increased sensitivity to activation by proteolysis. The increased activity of this protein in the intact cell was confirmed by its ability to stimulate expression from a phorbol-ester-inducible reporter construct in a transient transfection system. Expression of a mutant kinase with the pseudosubstrate sequence deleted causes greater induction in this transient expression system, consistent with this kinase being independent of effectors and thus constitutively active. PMID- 2253628 TI - Cloning and nucleotide sequence of cDNA encoding human liver serine-pyruvate aminotransferase. AB - Cloned cDNAs for human liver serine-pyruvate aminotransferase (Ser-PyrAT) were obtained by screening of a human liver cDNA library with a fragment of cDNA for rat mitochondrial Ser-PyrAT as a probe. Two clones were isolated from 50,000 transformants. Both clones contained approximately 1.5 kb cDNA inserts and were shown to almost completely overlap each other on restriction enzyme mapping and DNA sequencing. The nucleotide sequence of the mRNA coding for human liver Ser PyrAT was determined from those of the cDNA clones. The mRNA comprises at least 1487 nucleotides, and encodes a polypeptide consisting of 392 amino acid residues with a molecular mass of 43,039 Da. The amino acid composition determined on acid hydrolysis of the purified enzyme showed good agreement with that deduced from the nucleotide sequence of the cDNA. In vitro translation of the mRNA derived from one of the isolated clones, pHspt12, as well as that of mRNA extracted from human liver, yielded a product of 43 kDa which reacted with rabbit anti-(rat mitochondrial Ser-PyrAT) serum. Comparison of the deduced amino acid sequences of human Ser-PyrAT and the mature form of rat mitochondrial Ser-PyrAT revealed 79.3% identity. Although human Ser-PyrAT appears to be synthesized as the mature size, the 5'-noncoding region of human Ser-PyrAT mRNA contains a nucleotide sequence which would encode, if translated, an amino acid sequence similar to that of the N-terminal extension peptide of the precursor for rat mitochondrial Ser-PyrAT. PMID- 2253630 TI - Hepatic metastases in medullary thyroid carcinoma: possible pitfall with MR imaging. PMID- 2253629 TI - Cloning and sequence analysis of the genes encoding the dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase components of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. AB - A 2641-bp EcoRI fragment of DNA that encodes the C-terminal part of the dihydrolipoyl acetyltransferase (E2) component and the dihydrolipoamide dehydrogenase (E3) component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus has been cloned in Escherichia coli. Its nucleotide sequence was determined. A 705-bp truncated open reading frame was located at the 5'end of the insert which, together with the 588-bp truncated open reading frame at the 3' end of another EcoRI fragment of B. stearothermophilus DNA previously cloned and sequenced [Hawkins, C. F., Borges, A. & Perham, R. N. (1990) Eur. J. Biochem. 191, 337-446], was identified as the gene, pdhC, encoding the E2 polypeptide chain. Direct sequence analysis of the purified E2 chain confirmed that the two EcoRI fragments are adjoining in the B. stearothermophilus genome. The E3 gene, pdhD, begins just 4 bp downstream from the stop codon of the pdhC gene. The amino acid sequences deduced from the pdhC and pdhD genes correspond to proteins of 427 amino acids (E2, Mr 46,265) and 469 amino acids (E3, Mr 49,193), respectively. Both genes are preceded by potential ribosome-binding sites and the E3 gene is followed by a stemloop structure characteristic of rho-independent transcription terminators. The B. stearothermophilus E2 and E3 chains exhibit substantial sequence similarity with the corresponding subunits of other 2-oxo-acid dehydrogenase multienzyme complexes. The cloning and sequence analysis described here complete the description of the gene cluster (pdhA, B, C and D) which encodes the B. stearothermophilus pyruvate dehydrogenase multienzyme complex. PMID- 2253631 TI - Follow-up of regional myocardial T2 relaxation times in patients with myocardial infarction evaluated with magnetic resonance imaging. AB - Multi-echo spin-echo cardiac magnetic resonance imaging studies (echo times 30, 60, 90 and 120 ms) were performed in 19 patients with a 7-14-day (mean 10) old myocardial infarction and were repeated in 13 patients 4-7 months (mean 6) later. Also, 10 normal subjects were studied with magnetic resonance imaging. T2 relaxation times of certain left ventricular segments were calculated from the signal intensities at echo times of 30 and 90 ms. Compared to normal individuals, the mean T2 values on the early magnetic resonance images of the patients with inferior infarction showed significantly prolonged T2 times in the inferiorly localized segments, while on the follow-up magnetic resonance images the T2 times had almost returned to the normal range. Also the patients with anterior infarction showed significantly prolonged T2 times in the anteriorly localized segments on the early nuclear magnetic resonance images, but the T2 times remained prolonged at the follow-up magnetic resonance images. For every patient a myocardial damage score was determined, which was defined as the sum of the segmental T2 values in the patients minus the upper limit of normal T2 values obtained from the normal volunteers (= mean normal + 2SD). The damage score on both the early and late magnetic resonance imaging study correlated well with infarct size determined by myocardial enzyme release. Only the patients with an inferior infarction showed a significant decrease in damage score at follow-up magnetic resonance imaging. It is concluded that the regional T2 relaxation times are increased in infarcted myocardial regions and may remain prolonged for at least up to 7 months after the acute event, particularly in patients with an anterior infarction. These findings demonstrate the clinical potential of T2 weighted magnetic resonance imaging studies for detecting myocardial infarction, and estimating infarct size for an extended period after acute myocardial infarction. PMID- 2253632 TI - Use of non-ionic contrast media for tracheobronchography in neonates and young infants. AB - The paper describes the experience gained with tracheobronchography in 11 neonates and young infants with severe pulmonary disease--most of them on artificial respiration--using isotonic solutions of iopromide (17 series) and iotrolan (14 series). Both contrast agents were tolerated without any obvious problems when instilled into the lungs. Because of its higher content of iodine and greater viscosity, iotrolan was superior to iopromide as regards both the demonstration even of the more peripheral bronchial morphology and the duration of the contrast coating. PMID- 2253633 TI - Techniques of phlebography: a review. AB - Phlebographic techniques for ascending and descending phlebography, and varicography based on personal experience of over 15,000 examinations are described. The indications for their use and their interpretation are discussed. PMID- 2253634 TI - Contrast venography: from gold standard to 'golden backup' in clinically suspected deep vein thrombosis. AB - In a series of 180 patients, clinically suspected of having deep venous thrombosis (DVT), contrast venography was compared with radionuclide phlebography, duplex ultrasonography and strain gauge plethysmography. In most patients lung scintigraphy was also performed to detect pulmonary embolism (PE). Venography was performed on a routine basis. All venograms were read by at least two observers (radiologists or radiologist/resident) and an inter-observer agreement was reached of 96% with a kappa value of 0.935. In six patients venography was technically impossible or inadequate, 58% of the patients actually had DVT and 26% developed pulmonary embolism (PE). Of the patients with proven DVT, 43% developed PE. Of the three other methods duplex scanning scored the best for the detection of proximal thrombosis, with 92%, 90% and 9.2, and strain gauge plethysmography the worst, with values of 72%, 78% and 3.2 for, respectively, sensitivity, specificity and positive likelihood ratio's. On the basis of the presented material and the current literature it is concluded that the choice for a screening test for proximal thrombosis could best be made on the basis of (local) availability, cost-effectiveness and patient comfort. Duplex ultra sonography is tipped as the most promising method, accepting that distal thrombosis (calf veins) does not play an important role in PE. Contrast venography should be used as a 'golden backup' in any case of doubt. PMID- 2253636 TI - Computed tomography-guided scalp marking of cerebral surface lesions; an alternative to stereotaxis for small convexity lesions. AB - Marking of the skull prior to craniotomy on the basis of CT images can prove to be a difficult problem. The method reported here essentially consists of a procedure which involves tilting and manoeuvreing the head within the scanner so that the surface marker is perpendicular to the skull at the site of the lesion. This is easy, useful and not time consuming. PMID- 2253635 TI - CT and MR imaging of melanocytic schwannomas; report of three cases. AB - Melanocytic Schwannomas are rare tumours which can arise in soft tissues, spinal nerve roots and in the central nervous system. The literature suggests that they have a malignant behaviour with local recurrence after surgery. We present three patients with this lesion, two in the thoracic spine and one in the head of the pancreas. The clinical outcome in these cases has been disappointing, since two patients died from complications due to local spreading of the tumour in spite of surgery and radiotherapy. CT could not distinguish these tumours from other neurogenic neoplasms. When these tumours occur near the vertebral body, CT could only detect early bone erosion. MR findings show promising features, with a high signal on T1-weighted images, due to melanin. However, more experience is necessary to establish the possible specific features of melanocytic Schwannomas in MRI. PMID- 2253637 TI - Echographic patterns of just evolving acute pancreatitis: an experimental study. AB - The earliest echographic manifestations of just evolving acute pancreatitis were studied in five dogs. Fifteen minutes after induction of acute pancreatitis, the pancreas was excised. Serial echographic and microscopic cuts were performed in exactly corresponding levels of each pancreas. In all slices containing a pancreatic necrosis of 50% or more, the echographic pattern was abnormal. In extended pancreatic necrosis (i.e., 75-100% necrosis), a characteristic sonographic pattern could be observed, allowing differentiation from interstitial acute pancreatitis and minor necroses. PMID- 2253638 TI - Preoperative CT staging of colon carcinoma (excluding the recto-sigmoid region). AB - Twenty-eight patients with colon carcinoma (excluding the recto-sigmoid region) underwent preoperative staging with computed tomography (CT). The CT had a sensitivity and a specificity of 60 and 67% for detection of extramural invasion, 75% sensitivity and specificity for lymph node metastases and a sensitivity of 87% and specificity of 95% for liver metastases. Compared with the modified Dukes classification, CT correctly staged 50% of the patients with Dukes A lesions; 40% with Dukes B; 75% with Dukes C and 85% with Dukes D lesions. The data presented in this study showed that CT has limitations in the sensitivity and accuracy of staging local colonic carcinoma. However, we recommend its use for patients who are clinically suspected of having extensive disease. PMID- 2253639 TI - Metastatic malignant tumor in native kidney with acquired cystic disease after renal transplantation. AB - Patients on long-term hemodialysis frequently develop Acquired Cystic Renal Disease (ACRD). When hematuria or flank pain occurs, the possibility of malignant renal tumors should be investigated. We present an ACRD patient who received a kidney transplant and developed malignancy in a native kidney, the first manifestation being bone metastases, and discuss the role of CT in evaluating these patients. PMID- 2253640 TI - A rare acute pulmonary lesion after blunt chest trauma: a case report. PMID- 2253641 TI - Examination: what is best? PMID- 2253642 TI - CT-fluoroscopy link-up (CTF): potential for special procedures. AB - Some interventional radiological procedures call for unrestricted axial vision and monoplanar fluoroscopy at different angles. We have mounted a fluoroscopic image intensifier in front of the gantry of a CT scanner to assess whether the combination would be useful. This link-up has been tested in a variety of situations and, even with the shortcomings of makeshift equipment, the combination filled some gaps in our vision of what is going on inside the patient, especially before an invasive procedure. It also proved useful in the planning of multiple procedures in a single session, especially when they had to be performed under general anesthesia in children or in the management of critical cases. We feel that the possibilities afforded by CTF (computed tomography plus fluoroscopy) need further exploration prior to the construction of purpose-built equipment. The interim information supplied suggests that it will be worth developing. PMID- 2253643 TI - Ultrasonic diagnosis of ureteral calculi in patients with acute flank pain. AB - The diagnostic value of ultrasonography (US) and intravenous urography has been compared in a prospective study comprising 123 consecutive patients with severe acute flank pain of less than 72 hours' duration. Ultrasonography was performed transabdominally with a 5 MHz sector real-time transducer. Ureteral calculi were considered the final diagnoses in 46 patients, of which 35 with and 11 without accompanying hydronephrosis. Ureteral calculi were correctly diagnosed by US in 17 patients (sensitivity 37%). If hydronephrosis with or without calculus is included as a positive sign of ureteral calculus, a correct diagnosis was suggested by US in 34 patients (sensitivity 74%). We consider US to be a valuable method in patients with previous contrast media reactions, but recommend urography as the standard imaging method when renal colic is clinically suspected. PMID- 2253644 TI - Renal candidiasis: a case report showing the contribution of computed tomography. PMID- 2253645 TI - Value and limits of arthrography in the study of pathological mediopatellar plicae of the knee; a comparison with arthroscopy. AB - The results from arthroscopy and arthrography were compared in a prospective study of the mediopatellar plicae in 100 knees with internal disorders. With reference to arthroscopy, the sensitivity and specificity of arthrography for the detection of mediopatellar plicae were, respectively, 83.6 and 88.8%. The arthrographic signs of pathological plicae were: a thick plica, thicker than the internal condylar cartilage (sensitivity: 72%; specificity: 84%) and an interposed plica (sensitivity: 85%; specificity: 81.8%). Statistically the arthrographic signs agreed with the arthroscopic signs. The two methods did not differ significantly in their contribution to the diagnosis of pathological plicae. PMID- 2253646 TI - Osteosarcoma: correlation between radiological and histological changes after intra-arterial chemotherapy. AB - The statistical correlation between three different radiological methods (conventional radiography, computed tomography and angiography) and tumor necrosis (TN) of the resected specimen have been studied in a series of 31 patients diagnosed with osteosarcoma (OS). They were treated with a multidisciplinary approach including intraarterial and intravenous chemotherapy followed by limb salvage procedures, plus intraoperative radiotherapy and adjuvant chemotherapy. A clear statistical correlation has been obtained between TN and angiography (p = 0.02) and between TN and two specific radiological signs: 'tumoral stain and neovascularity' (p = 0.02) and 'peritumoral fat planes' (p = 0.05). Conventional radiography, computed tomography and other radiological signs studied (nutrient vessel, soft tissue mass and central peripheral calcifications) did not show any significant correlation with TN. These results seem to suggest that angiography is a method to evaluate TN preoperatively and also to define the efficacy of neoadjuvant chemotherapy in OS. PMID- 2253647 TI - Evaluation of first pass effect and biliary excretion of diperdipine in the dog. AB - Intravenous, oral and intraportal doses of diperdipine were given to bile duct cannulated dogs in order to assess the impact of first pass effect on the pharmacokinetics of this compound. After intravenous and oral doses, absolute bioavailability was calculated to be 18.7%. Biliary excretion accounted for about 0.1% of the total clearance of diperdipine and did not contribute to the overall elimination of the drug. After intraportal administration, the bioavailable fraction of diperdipine was increasing up to 44.3% suggesting a prehepatic site of loss of the drug. This was also substantiated by the fact that after oral administration a lesser fraction was excreted in the bile, than after the intraportal dose. The drug was highly bound to plasma proteins (greater than 96%) and was largely distributed in the blood cells for which a concentration dependent process was observed. PMID- 2253648 TI - Metabolism of difebarbamate in man. AB - The metabolism of 1,3-bis(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl- (1H,3H,5H)-pyrimidine-2,4,6-trione (difebarbamate) in man was studied. Human volunteers received a single oral dose of 25 mg/kg difebarbamate. Urine was extracted with Amberlite XAD-2 resin and the extracts were separated by preparative HPLC after enzymatic hydrolysis. Four major metabolites were isolated and their structures were determined using NMR and mass spectrometry. The oxygen dealkylation led to the formation of two metabolites: 1-(3-butoxy-2 carbamoyloxypropyl)-3-(2-carbamoyloxy-3-hydrox ypropyl)-5-ethyl-5- phenyl-(1H, 3H, 5H)-pyrimidine-2,4,6,-trione and 1,3-bis(2-carbamoyloxy-3-hydroxypropyl)-5 ethyl-5-phenyl-(1H,3H,5H )- pyrimidine-2,4,6,-trione. The hydrolysis of the carbamoyloxy group with the oxygen dealkylation led to the formation of 1-(2 carbamoyloxy-3-hydroxypropyl)-3-(2,3-dihydroxypropyl)-5-ethyl - 5-phenyl (1H,3H,5H)-pyrimidine-2,4,6,-tione, whereas the 4-hydroxylation of the benzene ring together with the oxygen dealkylation led to the formation of 1,3-bis(2 carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-(4-hydroxyphenyl )-(1H,3H,5H)- pyrimidine 2,4,6,-trione. No traces of the parent drug were found. PMID- 2253649 TI - Effect of experimentally-induced hepatic cirrhosis on the pharmacokinetics of orally administered praziquantel in the rat. AB - The effects of pretreatment with the hepatotoxin, thioacetamide, on the pharmacokinetics of praziquantel, a broad spectrum schistosomicidal agent with a high hepatic clearance, were studied in male Wistar rats. Animals were pretreated with either thioacetamide (25 mg in 100 ml of drinking water, n = 5) for 24 weeks or received plain drinking water (n = 5) over the same period. After the treatment period, praziquantel was administered orally (25 mg/kg as a 20 mg/ml solution in PEG 200) as a single dose. Blood samples (0.3 ml) were collected from the clipped tail at various times up to 4 h post administration. Plasma was analysed for praziquantel using an HPLC method. Mean peak plasma praziquantel concentrations were approximately 1.0 mg/l for both groups. The time to reach peak concentrations, and post-peak elimination half-life, were approximately 0.7 h and 1.0 h, respectively, for both groups. Similarly, mean AUC was approximately 2.0 mg.h/l for both groups. Statistical comparisons indicated that there were no significant differences in the pharmacokinetic parameters estimated in the two groups of animals. It was concluded that thioacetamide-induced hepatic cirrhosis has no effect on the pharmacokinetics of orally administered praziquantel in the rat, at the dose level studied. PMID- 2253650 TI - Evaluation of hepatic dysfunction in endotoxin pretreated rats using tolbutamide as a marker. AB - The pharmacokinetics of tolbutamide (TB) have been studied in endotoxin pretreated rats with the aim of evaluating TB as a marker for endotoxin effects. Endotoxin dose of 10 mg/kg resulted in a 50% rate of mortality. TB was i.v. administered 24 h. after endotoxin dosing. Clearance (Cl) decreased by approximately 2/3 of its value, area under the curve (AUC) and half-life (t1/2) in the pretreated animals were an average 1.5 times the values for the respective controls. Volume of distribution (Vd) increased by 10% approximately. These findings suggest that endotoxin pretreatment may cause hepatic damage by producing a decrease in Cl and an increase in the t1/2 of TB. But, SGOT levels in pretreated animals were not significantly different. This phenomenon may be explained by the increase in plasma protein binding of TB during endotoxin pretreatment, which decreases the free fraction of the drug in plasma available for metabolism. Endotoxin increased tmax of hydroxy-TB, while no change in Cmax was observed. Since tmax is inversely related to the formation and elimination rates of hydroxy-TB, an increase in tmax may be due to the decrease in both elimination rates. No change in Cmax may be due to the decrease in the rate of formation which is equivalent to the decrease in the rate of elimination of hydroxy-TB. PMID- 2253651 TI - Quantitative structure--pharmacokinetic relationship of a series of sulfonamides in the rat. AB - The pharmacokinetics of a series of sulfonamides were investigated after intravenous administration of a 7 mg/kg dose of individual sulfonamides to cannulated female lean Zucker rats. The concentrations of the sulfonamides in blood were determined by colorimetry. The blood concentration-time curves were fitted to a biexponential equation. The partition coefficient, log P, and pKa values of the sulfonamides were taken from the literature, log P and pKa values differed markedly across the series. The extent of protein binding varied enormously, increasing with partition coefficient. There was no significant relationship between the volume of distribution and partition coefficient. However, when the influence of protein binding on volume of distribution was eliminated, a significant linear relationship emerged. Total clearance formed a relatively complex nonlinear relationship with partition coefficient. The relationship of elimination half-life and partition coefficient was inverse of that between clearance and partition coefficient because of a lack of significant relationship between volume of distribution and partition coefficient. PMID- 2253652 TI - Pharmacokinetics of mitoxantrone in patients after 2 h and 24 h intra-arterial administration. AB - The pharmacokinetic parameters of mitoxantrone in patients with liver metastasis after intra-arterial 2 h and 24 h infusion (dosage 12 mg/m2) were investigated. Peak plasma concentrations were 305 +/- 60 ng/ml at 2 h infusion and 244 +/- 89 ng/ml at 24 h infusion. These peak plasma concentrations occurred at 0.9 +/- 0.8 h during 2 h infusion and 5.5 +/- 3.4 h during 24 h infusion. No significant difference between both intra-arterial administrations in elimination half-life (50-223 h at 2 h infusion, 58-246 h at 24 h infusion) and area under the plasma concentration-time curve (AUC0-72 = 11.6 micrograms/ml.h for 2 h infusion, AUC0 72 = 11.2 micrograms/ml.h for 24 h infusion) could be found. The results indicate that no change of availability in the central compartment at infusion of mitoxantrone over a period of 24 h could be achieved. The 2 h infusion lead to sufficient plasma levels with pharmacokinetic parameters of mitoxantrone similar to 24 h infusion and showed a good clinical picture with mild toxicity. PMID- 2253653 TI - Pharmacokinetics of oxiracetam in elderly patients after 800 mg oral doses, comparison with non-geriatric healthy subjects. AB - The pharmacokinetics of oxiracetam have been studied in eighteen elderly patients and in six healthy non-geriatric adults. A 800 mg single oral dose was administered in the morning of the first day and repeatedly, every 12 h, from day 2 evening to day 10 morning, to the elderly patients. The healthy non-geriatric adults were given a 800 mg single oral dose of oxiracetam. In healthy non geriatric subjects after a single oral administration of 800 mg, the normalized plasma levels of oxiracetam for 1 mg/kg dose were similar to those already recorded after a 2000 mg single dose of oxiracetam. Therefore, there was no tendency towards non-linear pharmacokinetics of oxiracetam between 800 and 2000 mg single doses in healthy subjects. After the single oral dose, the mean area under the plasma concentration-time curve of oxiracetam in elderly patients was increased by a factor of two as compared to that observed in non-geriatric healthy subjects whereas the maximum concentration (Cmax) was almost not modified and slightly delayed. This can be explained by a slower absorption and elimination in the elderly patients. The highest oxiracetam levels were predominantly recorded in the oldest patients. The slower elimination (mean T1/2 = 12.3 h in elderly and 7.7 h in healthy subjects) could be attributed to a physiological decrease of the renal function. The volume of distribution was not significantly modified in the elderly patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253654 TI - Pharmacokinetics of oxiracetam in patients with renal impairment after a 800 mg single oral dose. AB - The pharmacokinetics of oxiracetam in patients with renal impairment were investigated after administration of a 800 mg single oral dose of oxiracetam. The renal insufficiency was estimated on the basis of the creatinine clearance (CLcr) which ranged from 9 to 95 ml/min among the 20 patients. In plasma, the terminal elimination half-life (T1/2) ranged from 10.6 to 68.1 h, the highest T1/2 corresponding to the patients with a high degree of renal impairment. In urine, the amounts of oxiracetam excreted during the 48 h postdosing represented 8.3 to 82.6% of the dose. They were lower in patients with a high degree of renal impairment. The correlations between the total clearance of oxiracetam, the renal clearance, the terminal apparent elimination rate constant in plasma, and CLcr were estimated by linear regression analysis. The correlation coefficients were 0.916, 0.985 and 0.803 respectively. The apparent volume of distribution of the central compartment V(1) and the total volume of distribution at the steady-state V(SS) were not dependent on the degree of renal impairment. The mean values +/- SD were 25.9 +/- 13.0 litres and 48.3 +/- 21.5 litres respectively. Oxiracetam concentrations in plasma of patients were estimated for repeated administration of 800 mg of oxiracetam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253655 TI - Mephenytoin stereoselective elimination in the rat: III. Stereoselective time course of induction during chronic hepatic portal vein administration. AB - The blood concentrations of R- and S-mephenytoin were followed in seven rats over a 5-8 day period during a hepatic portal vein infusion of racemic mephenytoin. In all but two rats, both of the enantiomers achieved an initial steady-state level before a measurable change was observed in their blood concentrations. In each case, the decrease in the initial S-mephenytoin steady state blood level occurred after the change in R-mephenytoin was apparent. During the period of study, the mean +/- SD portal vein clearance of S-mephenytoin increased from 96 +/- 33 ml/h to 450 +/- 160 ml/h. The mean +/- SD portal vein clearance of R-mephenytoin increased from 170 +/- 50 ml/h to 2400 +/- 1600 ml/h. The larger increase in the portal vein clearance for the R-enantiomer resulted in the R/S-mephenytoin clearance ratio over this same time period changing from 1.8 +/- 0.2 to 5.2 +/- 1.8. Attempts to describe the time course of change in the clearance of S- or R mephenytoin using a previously reported model of induction were unsuccessful. The induction time course did suggest, however, that the rate of induction may be similar for each enantiomer. PMID- 2253656 TI - In vitro metabolism of cannabinol in rat, mouse, rabbit, guinea pig, hamster, gerbil and cat. AB - Metabolism of cannabinol (CBN) was studied in hepatic microsomal incubates from mouse, rat, rabbit, guinea pig, cat, hamster and gerbil. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS as TMS derivatives. Six monohydroxy metabolites were identified. These had hydroxy groups at C-11 and at all positions of the pentyl side-chain. Metabolism varied considerably between the species. 11-Hydroxylation was the most prominent route in the majority of species, but in the hamster and cat the major metabolic pathway was 4'-hydroxylation. Metabolites hydroxylated in the pentyl chain were generally more abundant in guinea pig, hamster and cat. PMID- 2253657 TI - Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation. AB - Steady-state plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were determined in 4 different groups of a total of 27 patients with ketamine long-term analgosedation (1.1 - 1.3 mg/kg/h). In 9 of the patients who had normal liver and kidney function (group 1), steady-state levels after 3 days of continuous infusion were 1.2 +/- 0.3 micrograms/ml ketamine, 1.0 +/- 0.6 micrograms/ml norketamine, and 2.6 +/- 1.0 micrograms/ml dehydronorketamine. The measured ketamine levels in group 1 were in agreement with the expected value, which may be calculated from published pharmacokinetic data after bolus injection. In 8 patients with acute renal failure (group 2), a tendency to about 20% higher ketamine steady-state plasma levels compared to group 1 was observed, but this difference was not significant. However, dehydronorketamine plasma levels were significantly higher in this group. Only a minor fraction of the ketamine dose (10% and 4%) was eliminated during hemodialysis or hemofiltration treatment, respectively. Steady-state plasma levels in 5 patients with cardiogenic shock (group 3) did not differ significantly from those of group 1. In 5 patients with long-term use of barbiturates (group 4), steady-state plasma levels of ketamine were significantly lower compared to groups 1 and 3, most likely due to barbiturate-induced enzyme induction. Hyperdynamic circulatory reactions were not observed in any of the patients. Psychomimetic effects could be excluded in 16 of the patients and were unlikely in 6 patients. In 5 further patients, psychomimetic effects could not definitely be excluded due to difficulties in non-verbal communication. PMID- 2253658 TI - Effect of furosemide on angiotensin II-mediated prostaglandin I2 production in hypertensive subjects. AB - The role of angiotensin II (AII) in Prostaglandin I2 (PGI2) production following furosemide has been examined in a placebo-controlled, cross-over study. Furosemide 20 mg was injected intravenously in eight hypertensive subjects already treated with oral captopril 25 mg or a matching placebo. Urinary excretion of 6-keto-PGF1 alpha (a metabolite of PGI2) and PGE2, PRA and AII was increased following furosemide without captopril pretreatment. The rises in urinary 6-keto-PGF1 alpha and PGE2, and plasma AII after furosemide were prevented by the captopril pretreatment. Urinary volume, sodium and furosemide were not affected by captopril. The data indicate that the effect of furosemide on PGI2 production, as reflected by the urinary excretion of 6-keto-PGF1 alpha, was mediated by an action of AII. PMID- 2253659 TI - Nocturnal oxygen saturation and body movement in asthmatics treated with controlled-release preparations of theophylline or terbutaline. AB - Nine adult asthmatics with a history of nocturnal symptoms and with morning dips in peak expiratory flow (PEF) were treated for 10-14 days with 24-h controlled release preparation of theophylline (Th), or a controlled-release preparation of terbutaline (Te), in a double-blind cross-over experiment. During treatment with 450-900 mg Th in the evening morning, plasma drug levels ranged from 53-95 (mean 73) mumol/l. The Te dose was 7.5 mg twice daily. Morning PEF values during Th (mean 338 l.min-1) and Te (316 l.min-1) were not significantly different. There were no significant differences between the treatments in average nocturnal oximetric O2 saturation (91.9% during Th and 91.0% during Te), or the amount of nocturnal body movement, recorded with a static charge sensitive bed (total number of movements 146 during Th and 120 during Te). No difference between the treatments was seen with respect to assessment by the subjects of sleep quality, which was considered fair or good. The findings suggest that in moderately severe asthma, nocturnal oxygenation and sleep quality were similar during the two treatments. PMID- 2253661 TI - Assessment of the systemic effects of inhaled glucocorticosteroids: the influence of blood sampling technique and frequency on plasma cortisol and leucocytes. AB - Twelve healthy males (mean age 27.6 y, range 23-35 y) took part in a randomized, double-blind, cross-over study of the effect of blood sampling technique (separate isolated venepunctures vs use of an IV cannula) and frequency (overnight vs morning) on plasma cortisol and white blood cell count after inhalation of a single dose of budesonide 3.2 mg or placebo, in order to establish the more sensitive method for future use. Sampling technique and frequency affected neither leucocytes nor plasma or urinary cortisol. Budesonide suppressed both plasma and urine free cortisol and delayed the nocturnal rise due to the circadian rhythm, thus reducing the AUC of plasma cortisol vs time. Lymphocytes, eosinophils and monocytes were decreased and neutrophils and total white blood cells were increased by the high dose of budesonide used. Lymphocytes and neutrophils showed significant changes earlier than eosinophils and cortisol and may be the variables of choice under certain conditions. Frequent sampling gave more complete information about the systemic effect of the drug than single morning samples. PMID- 2253660 TI - Effects of propranolol on ventricular repolarization in man. AB - The acute effects on monophasic action potentials (MAP), QT interval, and right ventricle effective refractory period (V-ERP) of propranolol 0.2 mg.kg-1 body weight have been studied in 10 patients with coronary artery disease. The median duration of MAP at 90% repolarization (MAP90) was shortened from 238 to 228 ms at a constant paced heart rate of 100 beats.min-1, while V-ERP remained unchanged. The median ratio V-ERP/MAP90 increased from 1.00 to 1.03. The electrical restitution curves of the duration of premature action potentials, normalized to those paced at constant heart rate, were more horizontal after propranolol. Isometric handgrip shortened MAP90 from 217 to 211 ms and after propranolol similar shortening was found (215 to 209 ms), although both values were slightly lower than before beta-blockade. PMID- 2253662 TI - Ibopamine-induced reduction of serum prolactin level and milk secretion in puerperal women. AB - Ibopamine, a peripheral dopamine agonist, was administered to 80 postpartum women to assess its effect on prolactin (PRL) and milk production. The acute administration of 400 mg significantly decreased serum PRL for more than 240 min. Women given ibopamine 400 mg t.d.s. for 5 to 10 days showed suppression of PRL and milk letdown was prevented in the latter group. No side effects were observed on repeated administration. Ibopamine may be a useful alternative to other dopaminergic compounds for the inhibition of puerperal lactation. PMID- 2253663 TI - Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics. AB - The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 microM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 microM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (-51%) and renal clearance (-33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00-14.00 h, 14.00-20.00 h) on Day 4 of the acetaminophen regimen. PMID- 2253664 TI - Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 micrograms. AB - In a Phase I study, the tolerability, pharmacodynamics and pharmacokinetics of cicaprost have been investigated in 6 male volunteers given 5, 10, 15 and 20 micrograms as tablets of the beta-cyclodextrin clathrate. Individual inhibition of platelet aggregation and changes in facial colour (measured by chromametry) were dose-dependent and reached a maximum 30 to 60 min post-dose. The maximum inhibition of platelet aggregation was about 40%. After 3 to 4 h pre-treatment values had returned. Blood pressure remained within the normal range. The peak plasma level of cicaprost was reached within 15 to 90 min after drug intake. Both Cmax- and AUC were individually dose-dependent. The terminal half-life in plasma of cicaprost was approx. 1 h, and its total clearance amounted to 4-7 ml.min-1.kg 1. The time courses of the plasma levels and of the pharmacodynamic actions were in agreement. Interindividual differences were observed in the occurrence of unwanted effects (e.g. headache). Thus, cicaprost is an orally available PGI2 mimetic, for which effects on platelet aggregation and vascular perfusion have been demonstrated in healthy volunteers after doses of 5 to 15 micrograms. PMID- 2253665 TI - Comparison of non-kinetic and kinetic approaches to individualization of gentamicin dosage. AB - A prospective study was carried out in 40 acutely ill patients to compare the non kinetic and kinetic approaches to individualization of the dosage regimen of gentamicin. The patients were divided into two equal groups. For the non-kinetic group, the doses were derived from the physician's personal experience, on a mg/kg basis, and by use of nomograms. The total daily dose ranged from 1.43 to 4.5 mg/kg. Based on serum concentration measurements, the dosage regimen for individual patient was calculated by Sawchuk-Zaske's method. The calculated doses were compared to the prescribed doses in each patient. Of the patients on empirically prescribed doses 65% received 36% more drug than the calculated dose and 20% received 36% less than the calculated dose. The calculated dosing intervals were greater than the recommended intervals in 60% of the patients. The gentamicin trough concentration was greater than 2 micrograms/ml in 70% of the patients. There was a significant tendency to overdosage of the patients. For the kinetic group, following administration of the calculated dose, the steady-state peak and trough concentrations in each patient were measured. The correlation of measured to predicted steady-state serum concentrations was excellent (r = 0.9968, p less than 0.05). About 85% of the served trough concentrations and 90% of the peak values fell within the therapeutic range. The mean of the prediction error (ME), mean absolute error (MAE), mean squared error (MSE), and root mean squared error (RMSE) of the trough and peak concentrations were calculated. The 95% confidence interval of the ME for the trough and peak concentrations included zero, which shows that the prediction was not significantly biased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253666 TI - Effect of age on single- and multiple-dose pharmacokinetics of erythromycin. AB - The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d. for 7 doses. The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses. Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively). The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h). No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution. The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults. Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance. The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people. PMID- 2253667 TI - Effect of ponsinomycin on cyclosporin pharmacokinetics. AB - The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin. On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption. Ponsinomycin should be use very carefully in patients treated with cyclosporin A. PMID- 2253668 TI - Medifoxamine: oral tolerance and pharmacokinetic study in healthy human volunteers. AB - Medifoxamine is a monoamine reuptake inhibiting antidepressant drug. We have investigated its pharmacokinetics in normal healthy volunteers. After an overnight fast, ascending doses of 200, 500, 750 and 1000 mg of medifoxamine were taken orally. Plasma samples were analysed using a specific HPLC method. Medifoxamine was well tolerated and exhibited a first order linear pharmacokinetic profile. It underwent rapid absorption and peak plasma concentrations were achieved about 1.0 h after administration. Thereafter the elimination profile was biphasic with a mean terminal half life less than 3 hours. We found a linear relationship (r = 0.80) between administered dose and AUC values for the four doses. High values were obtained for the apparent volumes of distribution and the plasma clearance. PMID- 2253669 TI - Variation of benzbromarone elimination in man--a population study. AB - The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes. PMID- 2253670 TI - Population pharmacokinetics of phenytoin in Singapore Chinese. AB - The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non linear mixed effect model, in the MULTI (ELS) program. There was no age or gender related effect on either the apparent maximum elimination rate (kmax) or Michaelis-Menten constant (KM). Kmax was related to body weight 0.656. The population pharmacokinetics was similar in children and adults. Kmax and KM were estimated to be 30.72 mg.kg-0.656 day-1 and 2.307 mg.l-1, respectively. Kmax was higher than reported values, and KM was comparable to that reported in a study in Japanese, but was much lower than that reported in studies of European patients. The inter-individual variability of KM (CV 65.58%) was substantially higher than that of kmax (CV 28.49%), and the residual (intra-individual) variability was found 21.33% (CV). PMID- 2253671 TI - Apparent racial difference in response to angiotensin I infusion. AB - Angiotensin I was infused into 16 healthy volunteers, 8 blacks and 8 whites with diastolic blood pressures below 75 mm Hg and the infusion rate increased at 3 min intervals until a diastolic blood pressure of equal to or greater than 95 mm Hg was achieved. Blacks exhibited a significantly greater angiotensin I sensitivity needing 1.8 micrograms/min as opposed to 3.9 micrograms/min in whites to achieve the target blood pressure. Plasma renin activities were similar in the two groups, but blacks had significantly higher urinary sodium values than whites, 223 mmol per 24 h as compared to 121 mmol per 24 h. It is concluded that the differences in response could be largely due to differences in dietary sodium intake. These factors need to be carefully considered when using angiotensin I infusion as a pharmacodynamic model for studying the effects of ACE inhibitors. PMID- 2253672 TI - Dose dependent enzyme induction by oxcarbazepine? AB - Antipyrine half life and clearance was compared in four patients with classical idiopathic trigeminal neuralgia during carbamazepine (CBZ) or CBZ/phenytoin (PHT) and after substitution with oxcarbazepine (OXC) monotherapy. OXC is observed to be less of a hepatic enzyme inducer than CBZ or CBZ/PHT in combination, however induction by OXC may be dose related. PMID- 2253673 TI - Bioinequivalence of marketed diltiazem preparations. AB - A bioequivalence study of three brands of regular diltiazem--Angizem (A), Dilzem (B) and Herbesser (C) has been carried out in 5 healthy, male volunteers. After a single oral dose of 60 mg of each preparation, the mean AUC (0-8 h) and Cmax of preparation B was significantly higher than of brands A and C. The tmax of A and B was significantly lower than of C. B had a higher dissolution rate in vitro (98.8% dissolved in 45 min) than A and C. Thus, there was bioinequivalence of the three brands of diltiazem, due partly to differences in dissolution and perhaps in part to a first pass effect. PMID- 2253674 TI - Pharmacokinetics of midazolam in critically ill neonates. AB - Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children. An IV bolus of midazolam 0.2 mg.kg-1 was administered to 10 critically ill neonates receiving intensive care who required sedation. The plasma clearance was 6.85 ml.min-1 and the elimination half-life was 6.52 h. Midazolam was well tolerated during and after administration. Because of its short half-life compared to diazepam, midazolam could be used during the neonatal period to produce brief rapid sedation. PMID- 2253675 TI - Pharmacokinetics and protein binding of methocarbamol in renal insufficiency and normals. AB - We determined plasma methocarbamol concentrations over 24 h following a 1.5 g methocarbamol dose (off-dialysis day) to 8 chronic haemodialysis patients and compared these results to those from 17 healthy male volunteers. The harmonic mean elimination half-life was similar between the two groups, 1.24 and 1.14 h, respectively. tmax and the weight-adjusted Cmax were 1.1 h and 27.0 mg.m-1 for haemodialysis patients and 1.1 and 23.1 mg.l-1 for normals. Relative systemic availability was assessed by comparing weight-normalized AUC x k10 products. These results indicate no significant differences with respect to methocarbamol absorption, with the relative systemic availability in patients being 113%. These data suggest that absorption and elimination of methocarbamol is similar between normal subjects and patients undergoing maintenance haemodialysis. PMID- 2253676 TI - Pharmacokinetics of various single intravenous and oral doses of omeprazole. AB - The influence of dose on the kinetics of omeprazole and two of its metabolites, hydroxyomeprazole and the sulphone, has been studied. Ten healthy subjects were given omeprazole 10 and 40 mg iv and 10, 40 and 90 mg orally. No significant dose related difference in any parameter calculated from the iv experiments was detected. Following the oral solutions, however, there was a dose-dependent increase in systemic availability, probably due to saturable first-pass elimination. The AUC of the sulphone also seemed to increase non-linearly with increasing dose, and that of the hydroxyomeprazole increased in proportion to dose. The slight dose-dependency of the bioavailability of the solution is considered to be of no or limited clinical relevance. Furthermore, since omeprazole is given orally as slowly absorbed enteric coated granules in the dose of 20 mg o.d., the potential for dose-dependent kinetics in clinical practice would be much less than in the present study. PMID- 2253677 TI - Chronokinetic study of netilmicin in man. AB - Netilmicin 1.5 mg/kg body weight was administered intravenously every 8 h for 2 days to 8 patients with normal renal function. Significant elevation of mean and trough plasma concentrations was found at 05.00 h and 09.00 h. This was considered to be due to circadian variation, with possible accumulation during the night. The clinical importance of this phenomenon in relation to the development of aminoglycoside toxicity awaits further investigation. PMID- 2253678 TI - Poly(Glu60Ala30Tyr10) (GAT)-induced IgG monoclonal antibodies cross-react with various self and non-self antigens through the complementarity determining regions. Comparison with IgM monoclonal polyreactive natural antibodies. AB - Previous studies have shown that the antibodies of the preimmune repertoire are able to bind to various auto- and xenoantigens including chemical haptens. Sequence analysis of two such murine monoclonal IgM natural autoantibodies showed that they are encoded by unmutated germ-line variable regions of the light and heavy chain (V alpha and VH) genes which were also found in various murine immune responses, like phenyl-oxazolone, dinitrophenyl, arsonate, phosphorylcholine and influenza virus hemagglutinin. These data raised the question as to whether induced antibodies possessing germ-line sequence are also able to react with autoantigens. To study this problem, anti-poly(Glu60Ala30Tyr10) (GAT) and anti alprenolol (Alp) monoclonal antibodies, carrying similar VH and V alpha genes and the same IgG1 isotype, were examined for their capacity to react with several self and non-self antigens. The results showed that: (a) the anti-GAT antibodies tested reacted with different autoantigens, such as murine tubulin, actin and myosin as well as trinitrophenyl (TNP) and bovine serum albumin. Similarly, one of the anti-Alp showed weak reactivities for myosin, DNA, actin and TNP; (b) in contrast two other anti-Alp antibodies did not react with any of the tested antigens. Since the major differences between the oligoreactive anti-GAT and the monoreactive anti-Alp antibodies are in the complementarity determining regions (CDR) our results suggest that the observed cross-reactions are mediated by hypervariable loops. Sequence comparison of these antibodies indicate a possible correlation between cross-reactivity and the presence of aromatic and charged amino acids in the CDR. PMID- 2253679 TI - Microenvironmental organization and stromal cell associations of B lymphocyte precursor cells in mouse bone marrow. AB - B lymphocyte precursor cells expressing B220 glycoprotein have been examined in mouse bone marrow (BM) by the in vivo binding of monoclonal antibody (mAb) 14.8 visualized by light and electron microscope radio autography. Young mice were injected intravenously with 125I-labeled mAb 14.8 and then perfused to remove unbound antibody. Quantitative analysis of radioauto graphic sections of femoral BM revealed many labeled mAb 14.8-binding cells which were situated both singly and in groups throughout the extravascular BM parenchyma. Groups of large 14.8+ cells were located in patchy areas in the peripheral regions of the BM near the endosteum. These cells were shown to include proliferating precursor B cells by using mice given vincristine sulfate to stop cells in metaphase and mice treated from birth with anti-IgM antibodies to delete mature B lymphocytes. Electron microscopy revealed clusters of 14.8+ cells intimately associated with the processes of stromal reticular cells. Other 14.8+ cells were in close contact with macrophages; in some instances the intervening cell membranes were indistinct and the macrophages contained 14.8+ material in their cytoplasm. In addition, 14.8+ small lymphocytes were highly concentrated within the lumen of some sinusoids. The present method of detecting B lineage precursor cells in situ has led to a working model of the microenvironmental organization of primary B cell genesis in vivo. The model proposes (a) a centrally directed sequence of differentiation initiated by early precursor cells situated peripherally near the surrounding bone; (b) close associations between precursor B cells and stromal reticular cells; (c) deletion of ineffective B cells by macrophages, and (d) an intravascular maturation phase before B lymphocytes are finally delivered into the blood stream. PMID- 2253680 TI - Spontaneous production of anti-mouse red blood cell autoantibodies is independent of the polyclonal activation in NZB mice. AB - New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation. PMID- 2253681 TI - Low IgG2 and polysaccharide response in a T cell receptor expression defect. AB - B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens. PMID- 2253682 TI - Characterization of B cell growth in systemic lupus erythematosus. Effects of recombinant 12-kDa B cell growth factor, interleukin 4 and transforming growth factor-beta. AB - B cells from systemic lupus erythematosus (SLE) patients have been shown to be hyperactive as measured by proliferation and immunoglobulin production. We find that B cells from 6 of 13 SLE patients, in the absence of prior activation, respond two to three times better to recombinant 12-kDa B cell growth factor (BCGF) than do normal or rheumatoid arthritis B cells (p less than 0.005). B cells from normally responsive SLE patients require an anti-mu antibody activation step to generate similar proliferative signal in response to r12-kDa BCGF. There are no clinical or serological parameters that distinguish these hyperresponsive SLE patients from the normally responsive SLE patients. The combination of r12-kDa-BCGF and interleukin 4 (IL4) gives an enhanced response with both normal and SLE B cells. Transforming growth factor type beta (TGF-beta) suppresses the response to r12-kDa-BCGF in a dose-dependent fashion using B cells from both healthy donors and SLE patients. We conclude that peripheral blood B cells are in an activated state (as detected by response to 12-kDa-BCGF) in approximately 50% of SLE patients. These B cells respond normally to regulation by IL4 and TGF-beta. A therapeutic approach aimed at reducing the B cell hyperactivity in SLE would involve suppressing the effects of 12-kDa-BCGF and IL4 while at the same time enhancing the effects of TGF-beta. PMID- 2253683 TI - The effect of mutations in the MHC class I peptide binding groove on the cytotoxic T lymphocyte recognition of the Kb-restricted ovalbumin determinant. AB - The H-2Kb-restricted cytotoxic T lymphocyte (CTL) response directed against ovalbumin (OVA) is specific for a region contained within the sequence OVA253 276. In this study we have characterized this response by examining the class I restricted presentation of OVA peptides by the naturally occurring Kb mutant (Kbm) glycoproteins Kbm1, Kbm3, Kbm5, Kbm8, Kbm10, Kbm11 and Kbm23. To facilitate this study we derived a series of somatic cell hybrid targets expressing the various Kbm class I molecules. Experiments using bulk OVA-specific CTL from C57BL/6 mice demonstrated that all the Kbm molecules except for Kbm1 and Kbm8 could present OVA peptides for effective T cell recognition. Clonal analysis revealed a more complex and relatively diverse pattern of CTL recognition of the Kbm/peptide combinations. This diversity is unlikely to result from the existence of multiple, independent Kb-restricted T cell determinants within OVA, since all CTL tested were specific for a single region between residues 259 and 273. Examination of the fine specificity of Kbm presentation identified individual changes at residues 77, 80 and 116 which affected T cell recognition. The results imply that these changes do not inhibit peptide binding since some clones could recognize peptide presented by a particular Kbm molecule, while other clones could not. All three residues reside within the peptide-binding cleft of the class I protein and are not expected to directly contact the T cell receptor. Although we did not formally demonstrate that OVA binding by Kbm vs. Kb is quantitatively identical, our results are best explained by postulating that the changes at residues 77, 80 and 116 indirectly affect T cell recognition by altering peptide conformation. Taken together our results suggest that changes within the class I binding site can profoundly modify peptide presentation without significantly inhibiting peptide-class I association. PMID- 2253684 TI - Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. AB - We have examined the effect of dexamethasone (DM) and cortisol on the production of interleukin (IL)6 from the murine macrophage cell line RAW264.9, human monocytes, human endothelial cells and the human fibroblast cell line FS4. In RAW264.9 cells DM in the concentration range 10(-9) M to 10(-6) M inhibited the lipopolysaccharide (LPS)-induced production of IL6 by 10% to 90%. Cortisol had a similar effect, but was about 25 times less potent than DM. Also, when 10(-6) M of DM was added to the cultures after addition of LPS, it completely inhibited the residual 24-h production of IL6. Corresponding to the effect on IL6 production, DM (10(-6) M) reduced the mRNA levels for IL6 in the RAW264.9 cells. The glucocorticoid analogue RU 486 competes with DM and cortisol for the glucocorticoid receptor and reversed the inhibitory effect of DM, demonstrating that DM exerts its effect via the glucocorticoid receptor. DM also had an inhibitory effect on LPS-stimulated IL6 production in freshly isolated human monocytes, and on IL 1-stimulated IL6 production in human endothelial cells and FS4 fibroblasts. These results demonstrate that DM via a receptor-mediated mechanism inhibits IL6 production at the transcriptional level, and this may contribute to the anti-inflammatory and immunosuppressive effect of glucocorticoids. PMID- 2253685 TI - Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro. AB - Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory [interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection. PMID- 2253686 TI - Autoimmune reactions to heat-shock proteins in pristane-induced arthritis. AB - The development of arthritis induced in mice by intraperitoneal injection of the non-antigenic mineral oil, 2,6,10,14-tetramethylpentadecane (pristane), was shown to depend on an intact immune response possibly to a heat-shock protein (hsp) in the synovium. Initial experiments suggested that some crucial event in the development of arthritis takes place early after pristane injection. First, irradiated pristane-treated mice failed to develop arthritis unless they were reconstituted with spleen cells from normal donors within 25 days of irradiation. Second, mice irradiated up to 50 days after pristane injection, but not later, did not develop arthritis. Evidence for the involvement of an immune response to heat-shock protein (hsp) comes from the finding that mice injected with mycobacterial 65-kDa hsp prior to pristane challenge had a reduced incidence of arthritis in contrast to animals pre-immunized with the E. coli hsp equivalent GroEL or with bovine serum albumin. Other experiments revealed that T cells from mice with gross morphologically defined arthritis proliferated strongly to hsp65 and to normal joint antigens, whereas T cells from animals treated with pristane which did not develop arthritis gave much smaller responses. Mice which developed arthritis also had elevated levels of anti-hsp65 IgG in comparison with non arthritic animals. These findings strongly suggest that autoimmune reactions to an antigen which cross-reacts with hsp65 are generated in pristane-induced arthritis. It is considered that the autoimmune response is directed to a synovial antigen and that pre-immunization with hsp65 protects the animals from the development of pristane-induced arthritis by altering the specificity or quality of the immune response to this antigen. PMID- 2253687 TI - Parasite-accessory cell interactions in theileriosis. Antigen presentation by Theileria annulata-infected macrophages and production of continuously growing antigen-presenting cell lines. AB - Theileria annulata, a protozoan parasite of cattle, infects major histocompatibility complex (MHC) class II+ cells, particularly macrophages, and transforms them into continuously growing cell lines. We examined the effects of parasitism by T. annulata on antigen-presenting cell function. T. annulata infected cells (TaH) presented ovalbumin (as measured by [3H]thymidine incorporation) to both resting autologous bovine T cells and ovalbumin-specific bovine CD4+ T cell lines. However, the former cells were also stimulated by TaH without exogenous antigen although to a lesser degree than in the presence of antigen. This "nonspecific" proliferation was not seen with the ovalbumin specific T cell lines. The magnitude of response by resting T cells in the presence of antigen, to TaH or purified peripheral blood monocytes, was essentially similar. However, on a per cell basis fewer TaH were required. Considerably greater proliferation to antigen was seen with the ovalbumin specific T cell lines in the presence of TaH compared to monocytes and again fewer TaH were required to elicit a response. The kinetics of processing did not appear to be substantially altered in TaH and the increased proliferation may be due to the elevated MHC class II expression of these cells. Genetic restriction studies with the T cell lines indicated that the restricting elements used to present ovalbumin by TaH were the same as those used by monocytes, as identified by an isoelectric focusing technique. The continuously growing cell lines provide us with a unique model for investigating parasite-accessory cell interactions in theileriosis. The augmented antigen presenting cell activity of TaH may play an important role in the pathogenesis of the disease. TaH will also provide us with a valuable resource for our antigen presentation studies. In particular, the enhanced antigen presentation by TaH enabled us to detect responses to lower levels of antigen, often an important consideration for experiments where the quantity of antigen available is the major limiting factor. PMID- 2253688 TI - Prostaglandin E2 as a selective stimulator of antigen-specific IgE response in murine lymphocytes. AB - Anti-2,4,6-trinitrophenyl (TNP) IgE antibody response was elicited by stimulating TNP-keyhole limpet hemocyanin-primed murine spleen cells with the same antigen in vitro. The released anti-TNP IgE was assayed by antigen- and isotype-specific enzyme immunoassay developed in our laboratory. When prostaglandin E2 (PGE2) was added to the lymphocyte culture at 10(-7) M, anti-TNP IgE response was augmented two- to fourfold. Interestingly, PGE2 did not affect the production of anti-TNP antibodies belonging to other isotypes including IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA. Moreover, PGE2 showed neither enhancing nor interleukin 4-replacing activities in the polyclonal IgE response by B cells stimulated with lipopolysaccharide and interleukin 4. When endogenous prostaglandin synthesis was inhibited by 10(-6) M indomethacin, the anti-TNP IgE response, but not the corresponding IgG response, was suppressed by 30%-60%. These results suggest a potential role of PGE2 in the up-regulation of the antigen-specific IgE response. PMID- 2253689 TI - Is the hypothesis alive that IgM anti-IgG1 rheumatoid factor specificity is determined by framework regions? PMID- 2253690 TI - Effects of inorganic cations on K(+)-, 5-hydroxytryptamine- and noradrenaline induced contractions of the isolated rat jugular vein and aorta. AB - We investigated the inhibitory effects of 1 mM of the inorganic cations, La3+, Cd2+, Mn2+, Ni2+ and Co2+ on contractions induced by K+ (100 mM) and 5 hydroxytryptamine (5-HT, 10(-5) M) in the isolated rat jugular vein and on contractions induced by K+ (100 mM), 5-HT (10(-5] and noradrenaline (NA, 10(-5) M) in the rat aorta. In the venous preparation, both K(+)- and 5-HT-induced Ca2+ influx could be suppressed completely by all cations studied. In the aorta, the K(+)-induced Ca2+ influx was antagonized completely only by Cd2+. The other cations were less effective and Mn2+ was completely ineffective. Similarly to that in the venous preparation, the 5-HT-induced Ca2+ influx in the aorta was abolished by all the cations. A similar picture was found for the NA-induced Ca2+ influx with the exception of Mn2+, which antagonized the NA-induced contractions only slightly. Although organic calcium entry blockers (CEBs) (nifedipine, diltiazem, flunarizine and gallopamil) inhibited NA-induced contractions to the same extent as did Mn2+, a combination of organic CEBs and Mn2+ abolished the NA induced Ca2+ influx completely. Apparently, organic CEBs and Mn2+ block different components of the NA-induced Ca2+ influx pathway. PMID- 2253691 TI - Morphine attenuation of a conditioned emotional response in post-dependent rats. AB - Rats placed in a test chamber where they had received repetitive shocks the previous day significantly reduced their motor activity; this was taken as indicator of a conditioned emotional response. Morphine attenuated this conditioned suppression of motility, possibly due to a reduction of the anxiety associated with the expectation of the noxious stimuli. Previous morphine dependence (20 mg/kg daily for 26 days) did not modify the effect of the opioid on the conditioned suppression of motility. This fact suggests that the action of morphine on pain anticipatory anxiety is similar in non-dependent and in post dependent rats. Opioids are considered to produce pain relief in part by decreasing the anticipatory anxiety. The present results thus indicate that this important component of the analgesic action of morphine is unchanged in post addicts. PMID- 2253692 TI - Direct evidence for the involvement of vasoactive intestinal polypeptide in the motor response of the human isolated ileum to capsaicin. AB - Capsaicin (1 microM) produced complex motor responses in longitudinal and circular muscle strips from the human isolated small intestine (jejunum and ileum). In the longitudinal muscle, inhibition of the nerve-mediated contractions (electrical field stimulation) was the dominant response, while capsaicin had a weak and inconsistent effect on tone and spontaneous activity. In contrast, relaxation and decreased spontaneous activity were the responses of the circular muscle to capsaicin. These effects of capsaicin were not reproduced by a second application of capsaicin, indicating desensitization, a feature of the specific action of this drug on sensory nerves. All the effects of capsaicin in the longitudinal and circular muscle were closely mimicked by exogenous vasoactive intestinal polypeptide (VIP). Further, the inhibitory motor effect of capsaicin in both muscle layers was blocked by an anti VIP serum. In the longitudinal muscle, VIP, like capsaicin, inhibited the electrically evoked nerve-mediated contractions but not the tetrodotoxin-resistant myogenic contractions, suggesting a prejunctional site of action. The inhibitory effect of both capsaicin and VIP in the circular muscle was tetrodotoxin-resistant suggesting direct inhibition of muscle cells. Capsaicin (1 microM) evoked a tetrodotoxin-resistant release of VIP like immunoreactivity from the human small intestine. On high pressure liquid chromatography, a major peak of the immunoreactive material released by capsaicin co-eluted with authentic VIP and a minor, unidentified peak eluted shortly afterward. We conclude that authentic VIP is involved in the local motor response to capsaicin in the human small intestine. These findings raise the possibility that VIP might be present in sensory nerves of the human gut from which it is released by capsaicin. PMID- 2253693 TI - Theophylline concentration in the extracellular space of the rat brain: measurement by microdialysis and relation to behaviour. AB - The free extracellular concentration of theophylline in the brain was estimated from microdialysis samples. Two different methods were used to estimate extracellular concentrations by microdialysis, the perfusion rate method and the difference method. Theophylline 20 mg/kg (s.c.) gave a sufficiently stable level of theophylline in the brain 60 min after injection and lasting over the observation period to allow application of the two methods in vivo. The relation between dose and dialysate concentration was linear. It was found that doses of 20-24 mg/kg theophylline corresponded to a free extracellular concentration of 60 90 microM. The behaviour of theophylline-treated rats was assessed in parallel experiments by means of a holeboard apparatus. Behavioural activation was observed in the dose-range 3-30 mg/kg. It is concluded that behavioural effects of theophylline can be induced at a concentration well below that required to inhibit phosphodiesterase but within the range in which adenosine receptor blockade may be observed, suggesting that the latter mechanism is responsible for the behavioural effects of theophylline. PMID- 2253694 TI - Localization of peripheral cholecystokinin receptors in vivo using the cholecystokinin antagonist [3H](+/-)-MK-329. AB - Cholecystokinin (CCK) regulates various gastrointestinal functions through specific receptors. The mechanisms responsible for disorders of these functions could be elucidated by non-invasively localizing CCK receptors and quantifying their number in vivo. MK-329 is a highly selective and very high affinity antagonist at the peripheral CCK receptor. We investigated the in vivo binding of [3H](+/-)-MK-329 in mice to determine if binding to CCK receptors could be detected after systemic administration of the tracer. The uptake of [3H](+/-)-MK 329 increased in the pancreas from 5 min to 4 h after administration. The binding was saturable, stereospecific, and more than 80% specific. A total/non-specific binding ratio of 43 was reached at 8 h post-injection. The pancreas was the only organ where specific binding could be detected. Our results suggest that MK-329 labeled with a positron emitter such as C-11 could be used with positron emission tomography to image and quantify peripheral CCK receptors in man. PMID- 2253696 TI - p-Fluoro-hexahydro-sila-difenidol: affinity for vascular muscarinic receptors. AB - The M3-selective antagonist, p-fluorohexahydro-sila-difenidol was used to characterize muscarinic receptors in two vascular preparations, the rabbit ear artery with an endothelium-dependent relaxation and the bovine coronary artery with an endothelium-independent contractile response. pKB values were consistent with the presence of M3 receptors, 7.9 and 7.5 in coronary and ear arteries, respectively. These findings confirm that muscarinic receptors of the rabbit ear artery and bovine coronary artery have similar characteristics and belong to the M3 subtype. PMID- 2253695 TI - Effects of chronic treatment of MPTP monkeys with bromocriptine alone or in combination with SKF 38393. AB - Eight monkeys developed a severe parkinsonian syndrome after i.v. administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with bromocriptine (5 mg/kg) relieved the parkinsonian symptoms, but the efficacy of this treatment appeared to decrease slightly with time. The addition of SKF38393 (5 mg/kg) to the bromocriptine treatment in four monkeys prevented and even reversed the tendency to decreased efficacy with an increased response in three out of four animals. Neither of these two treatments induced dyskinesia in these monkeys. Dopamine D1 and D2 receptors, assayed in the caudate nucleus, the putamen and nucleus accumbens with [3H]SCH 23390 and [3H]spiperone binding respectively, were not significantly different in MPTP monkeys treated with bromocriptine or with bromocriptine plus SKF38393. Monkeys in the two treatment groups had a similar extent of denervation of the striatum and accumbens as assessed by the content of dopamine and its metabolites. These results suggest that in MPTP monkeys, the behavioral response to the D2 agonist bromocriptine can be enhanced by concomitant activation of the D1 receptors while this combination of agonists does not induce dyskinesia. The addition of the D1 agonist does not appear to cause further alteration of the D1 or D2 receptors. PMID- 2253697 TI - 5 alpha-Pregnan-3 alpha-ol-20-one blocks nicotine-induced seizures and enhances paired-pulse inhibition. AB - 5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) blocked seizures induced by nicotine (4 mg/kg, i.p.) in C3H male mice with an ID50 of 2.37 +/- 0.66 mg/kg (average +/- 95% confidence limit). This steroid (1 microM) also increased paired pulse inhibition in the hippocampus approximately 40% after 50 min exposure; nicotine (200 microM) partially reversed this effect. Since nicotine and 3 alpha OH-DHP may have opposite effects on endogenous inhibitory systems, it is proposed that nicotine-induced seizures may involve a disinhibitory mechanism and that 3 alpha-OH-DHP protects against seizures by preventing disinhibition. PMID- 2253698 TI - Oxiracetam increases the release of endogenous glutamate from depolarized rat hippocampal slices. PMID- 2253699 TI - Hypothalamic vasopressin mRNA levels in mice are decreased after chronic ethanol ingestion. AB - Vasopressin mRNA levels in the supraoptic and paraventricular nuclei of the hypothalamus, measured by in situ hybridization with a 35S-labeled RNA probe, were decreased by nearly 50% in C57BL/6NCR mice that had ingested an ethanol containing diet for 7 days, and were tolerant to and physically dependent on ethanol. At 24 h after withdrawal, vasopressin mRNA levels in the supraoptic nucleus were still decreased, while levels in the paraventricular nucleus returned toward control values. Although plasma osmolality was increased in ethanol-fed mice, there was no increase in plasma vasopressin levels, possibly as a result of the effect of chronic ethanol ingestion to decrease vasopressin synthesis. In contrast, in mice that were dehydrated, but not fed ethanol, plasma osmolality, plasma vasopressin levels, and hypothalamic vasopressin mRNA all increased, as expected. The data suggest that chronic ethanol ingestion interferes with the synthesis and secretion of vasopressin, and may result in the reduced ability of an individual to respond to physiological stimuli for vasopressin secretion. PMID- 2253700 TI - Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4. AB - The goals of the present study were: (1) to investigate the binding properties of (R)- and (S)-procyclidine and two achiral derivatives of muscarinic M1, M2 and M4 receptor subtypes and (2) to identify the interactions which allow these receptors to discriminate between the two stereoisomers. (R)-Procyclidine showed a higher affinity for human neuroblastoma NB-OK 1 muscarinic M1 and rat striatum muscarinic M4 receptors, as compared to rat cardiac M2 receptors. (S) Procyclidine had a 130-fold lower affinity than (R)-procyclidine for M1 and M4 receptors, and a 40-fold lower affinity for M2 receptors. Pyrrinol, the achiral diphenyl derivative with the cyclohexyl group of (S)-procyclidine replaced by a phenyl group, has an eight-fold lower affinity for M1 and M4 receptors, as compared to (R)-procyclidine, and a three-fold lower affinity for M2 receptors. Hexahydro-procyclidine, the corresponding achiral dicyclohexyl compound, had a 10 to 20-fold lower affinity than (R)-procyclidine for the three receptors. The increase in binding free energy, which is observed when the phenyl and cyclohexyl groups of procyclidine are separately replaced by cyclohexyl and phenyl groups, respectively, was additive in the case of M1, M2 and M4 receptors. This indicates that the muscarinic receptor stereoselectivity was based on the coexistence of two binding sites, one preferring a phenyl rather than cyclohexyl group and the second preferring a cyclohexyl rather than a phenyl group. In addition, there were also binding sites for the hydroxy moiety and the protonated amino group of the ligands. The greater affinity and stereoselectivity of M1 and M4 muscarinic receptors for (R)-procyclidine reflected the better fit of the cyclohexyl group of (R)-procyclidine to the subsite of M1 and M4 as compared to M2 receptors. PMID- 2253701 TI - Reduction of phosphate-induced dysfunction in rat heart mitochondria by carnitine. AB - The direct effects of varying concentrations (5-40 mM) of D,L-carnitine were studied in two populations, subsarcolemmal and interfibrillar, of cardiac mitochondria exposed to inorganic phosphate (Pi). After 5 min preincubation 20 mM Pi significantly depressed oxidative phosphorylation rate and ADP/ATP translocase activity, in both populations. Inclusion of D,L-carnitine during preincubation significantly prevented the Pi-induced depression in oxidative phosphorylation without affecting the ADP/ATP translocate system. The Pi-induced inhibition in mitochondrial oxygen consumption rate was seen with either pyruvate-malate, glutamate-malate or succinate as respiratory substrates and was also observed in uncoupled mitochondria treated with 2,4-dinitrophenol. Mitochondrial swelling and shrinkage studies revealed Pi-induced inner membrane instability, a phenomenon prevented by D,L-carnitine in a dose-dependent manner. The effect of Pi was also observed at a concentration of 5 mM which was also prevented by carnitine. Mepacrine, a phospholipase A2 inhibitor, failed to prevent any of the effects of Pi. The results therefore suggest that Pi can produce a depression in mitochondrial oxidative phosphorylation through a mechanism possibly associated with disturbed inner membrane structure and function but apparently unrelated to phospholipase A2 activation. The salutary actions of carnitine may partly explain its protective effects in the ischemic and reperfused heart, a phenomenon associated with enhanced intracellular Pi accumulation. PMID- 2253702 TI - Characteristics of inositol 1,4,5-trisphosphate binding to rat cerebellar and bovine adrenal cortical membranes: evidence for the heterogeneity of binding sites. AB - The equilibrium and kinetic binding characteristics of D-inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) have been studied in membrane preparations of rat cerebellum and bovine adrenal cortex. Saturation analysis of isotopic dilution binding data demonstrated apparent KD values for Ins(1,4,5)P3 binding of 23 +/- 5 nM and 3.0 +/- 1.3 nM for cerebellar and adrenal cortical preparations, respectively, with approximately 20-fold greater receptor density present in the cerebellar preparation (Bmax: 10.2 +/- 2.5 pmol/mg protein). Kinetic analysis confirmed the equilibrium binding-derived KD value for cerebellum (KD: 39.9 nM), but revealed a second, very high affinity site (KD: 0.06 nM) to be present in adrenal cortex. The affinity differences between the investigated preparations was also observed with respect to the IC50 values obtained for inhibition of specific [3H]Ins(1,4,5)P3 binding by a number of inositol polyphosphate analogues including D-inositol 2,4,5-trisphosphate, DL-inositol 1,4,5-trisphosphorothioate and L-Ins(1,4,5)P3. In contrast, the Ins(1,4,5)P3-receptor antagonist heparin displayed greater potency for the cerebellar (IC50: 16.5 +/- 6.2 micrograms . ml 1) compared to the adrenal cortical preparation (IC50: 51.0 +/- 6.1 micrograms . ml-1). The apparent differences between the Ins(1,4,5)P3 receptors characterized in the two tissue preparations are discussed. PMID- 2253703 TI - Muscarinic acetylcholine receptors in the sino-atrial node and right atrium of bovine heart. AB - Muscarinic acetylcholine receptors were identified by the specific binding of [H](-)quinuclidinylbenzilate [( 3H](-)QNB) and [3H]oxotremorine-M [( 3H]Oxo-M), to membranes isolated from the sino-atrial (SA) node and right atrium (RA) of bovine heart. The density of [3H](-)QNB binding sites was greater in the SA node compared to the RA. Specific [3H](-)QNB binding was saturable and occurred to a single population of binding sites in both regions. The binding of antagonists, as assessed by competition with [3H](-)QNB, also occurred to a single population of sites; the binding affinities of all antagonists were similar in either region. Agonist competition curves, except for McN-A-343, were complex and computer analyses indicated that agonists bound to at least two populations of binding sites that differed in affinity. The proportion of high-affinity agonist binding sites was consistently greater in the SA nodal, relative to the RA membranes, while the affinity of the high-affinity agonist binding sites to a given agonist was essentially similar in either region. The high-affinity binding of [3H]Oxo-M was saturable and occurred to a single population of sites. The maximal binding of [3H]Oxo-M in the SA nodal membranes was higher than in the RA membranes. Guanine nucleotides and N-ethylmaleimide (NEM) markedly decreased [3H]Oxo-M binding; NEM did not appear to influence guanine nucleotide-dependent decrease in [3H]Oxo-M binding. Phospholipase A2 decreased both [3H](-)QNB and [3H]Oxo-M specific binding, the latter being affected to a greater extent. Phospholipase C also decreased [3H](-)QNB and [3H]Oxo-M binding, although to a lesser degree compared to phospholipase A2. Either lipase, however, increased the guanine nucleotide-sensitive agonist binding. Analysis of [3H](-)QNB binding to microsomal subfractions showed that binding sites were enriched in the light plasma membrane fractions that were also enriched in pertussis toxin sensitive guanine nucleotide binding proteins. PMID- 2253704 TI - Characterization of 5-HT3 receptors in intact N1E-115 neuroblastoma cells. AB - The highly selective 5-HT3 receptor antagonist [3H]GR65630 has been used to characterize 5-HT3 receptors in intact N1E-115 neuroblastoma cells. Equilibrium binding analysis demonstrated high-affinity binding to a single class of receptors with a Kd of 0.69 (+/- 0.12) nM and Bmax of 31.4 (+/- 11.4) fmol/10(5) cells, equivalent to approximately 200,000 sites per cell. Specific binding was displaced by low concentrations of 5-HT3-selective ligands, and by the nicotinic antagonist d-tubocurarine. PMID- 2253706 TI - Genetic code 1990. PMID- 2253705 TI - Target size of 5-HT3 receptors in N1E-115 neuroblastoma cells and rat brain. AB - Radiation inactivation was used to determine the molecular target size of the binding site for [3H]GR65630, a specific 5-HT3 receptor ligand, in two different neuronal tissues. Using a calibration curve of known molecular weight enzymes, the target sizes of [3H]GR65630 binding sites in N1E-115 neuroblastoma cells and rat brain were 98,600 +/- 11,300 and 49,100 +/- 8,500 Da, respectively. The results suggest 5-HT3 receptors may be present as dimers in N1E-115 neuroblastoma cells. PMID- 2253707 TI - The accuracy of aminoacylation--ensuring the fidelity of the genetic code. AB - The fidelity of protein biosynthesis rests not only on the proper interaction of the messenger RNA codon with the anticodon of the tRNA, but also on the correct attachment of amino acids to their corresponding (cognate) transfer RNA (tRNA) species. This process is catalyzed by the aminoacyl-tRNA synthetases which discriminate with remarkable selectivity amongst many structurally similar tRNAs. The basis for this highly specific recognition of tRNA by these enzymes (also referred to as 'tRNA identity') is currently being elucidated by genetic, biochemical and biophysical techniques. At least two factors are important in determining the accuracy of aminoacylation: a) 'identity elements' in tRNA denote nucleotides in certain positions crucial for protein interactions determining specificity, and b) the occurrence in vivo of competition between synthetases for a particular tRNA which may have ambiguous identity. PMID- 2253708 TI - Prokaryotic genetic code. AB - The prokaryotic genetic code has been influenced by directional mutation pressure (GC/AT pressure) that has been exerted on the entire genome. This pressure affects the synonymous codon choice, the amino acid composition of proteins and tRNA anticodons. Unassigned codons would have been produced in bacteria with extremely high GC or AT genomes by deleting certain codons and the corresponding tRNAs. A high AT pressure together with genomic economization led to a change in assignment of the UGA codon, from stop to tryptophan, in Mycoplasma. PMID- 2253709 TI - The genetic code in mitochondria and chloroplasts. AB - The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences. PMID- 2253712 TI - Hypoxia: on the borderline between physiology and pathophysiology. PMID- 2253713 TI - Hypoxia: on the borderline between physiology and pathophysiology. A foreword. PMID- 2253710 TI - Codon context. AB - The analysis of coding sequences reveals nonrandomness in the context of both sense and stop codons. Part of this is related to nucleotide doublet preference, seen also in non-coding sequences and thought to arise from the dependence of mutational events on surrounding sequence. Another nonrandom context element, relating the wobble nucleotides of successive codons, is observed even when doublet preference, codon usage and bias in amino acid doublets are all allowed for. Several phenomena related to protein synthesis have been shown in vivo to be affected by the nucleotide sequence around codons. Thus, nonsense and missense suppression, elongation rate, precision of tRNA selection and polypeptide chain termination are all affected by codon context. At present, it remains unclear how these phenomena may influence the evolution of nonrandomness in the context of codons in natural sequences. PMID- 2253711 TI - Suppression and the code: beyond codons and anticodons. AB - Specificity and accuracy in the decoding of genetic information during mRNA programmed, ribosome-dependent polypeptide synthesis (translation) involves more than just hydrogen bonding between two anti-parallel trinucleotides, the mRNA codon and the tRNA anticodon. Other macromolecules are also involved, and translational suppression has been and continues to be an appropriate and effective way to identify them, as well as other parts of mRNA and tRNA, and to elucidate the structural determinants of their functions and interactions. Experimental results are presented that bear upon codon context effects, the role of tRNA structural features in aminoacyl-tRNA selection and in codon selection (reading-frame maintenance), determinants of tRNA identity, elongation factor suppressor mutants, and termination codon recognition by the ribosomal RNA of the small subunit. The examples presented illustrate the complexity of the decoding process and the interconnectedness of translational macromolecules in achieving specificity and accuracy in polypeptide synthesis. PMID- 2253714 TI - Contribution of diffusion to the oxygen dependence of energy metabolism in cells. PMID- 2253716 TI - Myocardial force production and energy turnover in anoxia. AB - ATP turnover of isolated rabbit papillary muscles, contracting isometrically at 20 degrees C, was determined in oxygen and during 40 min of exposure to nitrogen (anoxia). Stimulus frequency was 0.2 hertz (Hz) in oxygen and 0.2 or 1.0 Hz in nitrogen. In oxygen, ATP turnover was determined from oxygen consumption using a P/O2 ratio of 6.3. The time-dependent rate of ATP turnover in nitrogen was found from the production of lactate, and the changes in adenine nucleotides and phosphocreatine, measured in rapidly frozen preparations at different time-points during the anoxic period. A P/lactate ratio of 1.5 was used. In muscles stimulated at 0.2 Hz, twitch force dropped during the anoxic period to 33% while force production of muscles stimulated at 1.0 Hz stopped completely. However, in the latter muscles, resting force rose to 19% of the twitch force in oxygen. The rate of ATP hydrolysis in anoxia depended strongly on stimulus frequency, indicating that it is not solely determined by the glycolytic capacity. In the 0.2 Hz-stimulated muscles the decrease in energy turnover occurred in parallel with the drop in force. However, the rise in resting force in muscles stimulated at 1.0 Hz occurred when ATP turnover was close to zero. It was concluded that anoxia hardly affects the energy required for twitch force production, but that the rise of resting force measured when twitch force had disappeared occurred when the rates of cross-bridge cycling and calcium turnover were very low. PMID- 2253715 TI - Consequences of acute ischemia for the electrical and mechanical function of the ventricular myocardium. A brief review. AB - Reduction or interruption of the blood supply to the myocardium leads to marked disturbances of electrical and mechanical function within a few seconds. Electrical dysfunction is characterized by an initial depolarization of the resting membrane, and a decrease of the amplitude, the upstroke velocity and the duration of the action potential. Both depolarization and depression of the action potential are closely associated with intracellular metabolic acidosis. After this initial phase, electrical cell-to-cell uncoupling develops, probably as a consequence of increased cytosolic free [Ca++]. Mechanical dysfunction is characterized by a dissociation of the initial decrease of active force development from the subsequent ischemic contracture. Active force development in acute ischemia is inhibited by the accumulation of ischemic metabolic products (H+, inorganic phosphate (Pi), Mg++) but not by a marked decrease of [ATP]. The subsequent ischemic contracture is probably initiated by release of Ca++ from intracellular stores. This release causes rapid consumption of ATP and the development of rigor within 1-2 minutes. PMID- 2253717 TI - Adenosine is a sensitive oxygen sensor in the heart. AB - Cardiac adenosine is formed both by an oxygen-sensitive (AMP----adenosine) and by an oxygen-insensitive (S-adenosylhomocysteine----adenosine) pathway. The phasic adenosine release during beta-adrenergic stimulation with isoproterenol is closely linked to coronary venous PO2 (isolated heart) and can be almost fully prevented when diastolic aortic pressure is maintained constant (heart in situ). During pressure autoregulation the transmural gradient of free adenosine is only increased when the autoregulatory reserve is exhausted. The critical PO2 below which adenosine formation is enhanced was found to be 3 mm Hg (isolated cardiomyocytes). Collectively, these data indicate that the formation of adenosine is not primarily coupled to the energy expenditure of the heart but to the supply/demand ratio for oxygen. PMID- 2253718 TI - Endothelial cells as part of a vascular oxygen-sensing system: hypoxia-induced release of autacoids. AB - Higher developed organisms are equipped with many central and local control mechanisms, which enable an adequate blood and oxygen supply to tissues over a wide range of demands. Global adaptive responses include changes in the circulatory and ventilatory system as well as increases in the oxygen carrying capacity of the blood. At the level of the specialized organs there exist additional control systems for the regulation of local blood flow. Most systems make use of highly specialized cells which are able to sense the oxygen partial pressure of the transport medium, blood, and within the tissues. In the past years, it has been shown that the vascular endothelium lining the entire circulatory system can actively modulate the vascular tone and platelet functions by the release of autacoids, among them prostacyclin and endothelium-derived nitric oxide (EDRF). Recent experiments demonstrate that the release of EDRF is PO2-dependent, which suggests that endothelial cells may act as functional local oxygen sensors within the vascular system. PMID- 2253719 TI - Defining the resistance to oxygen transfer in tissue hypoxia. AB - Studies of O2 supply in freshly isolated adult mammalian cells provide new insight into the factors that limit mitochondrial oxygenation in vivo. Of particular importance, mitochondria are present at high densities and often in apparent clusters, both of which contribute to local O2 gradients under hypoxic conditions. Current evidence indicates that the mitochondrial distribution is a component of the differentiated phenotype of adult mammalian cells and that specific motors and anchoring mechanisms are present to allow redistribution in response to developmental, physiological and pathological challenges. To compare the importance of resistance to O2 transfer under different conditions and at different sites along the supply path in vivo, a simple mathematical expression of relative resistance to O2 supply is introduced. Under various pathophysiological conditions, this resistance increases in specific regions of the pulmonary, circulatory or cellular supply path and results in O2 deficiency in the mitochondria. Regardless of cause, the relative resistance increases dramatically in the vicinity of mitochondrial clusters during hypoxia. PMID- 2253720 TI - Human muscle structure after exposure to extreme altitude. AB - Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed on muscle biopsies. A significant reduction in muscle fiber size (-20%) and a loss of muscle oxidative capacity (-25%) were observed. The capillary network was not affected by catabolism. It is concluded that the oxygen supply to muscle mitochondria after high altitude exposure is thus improved. PMID- 2253721 TI - On maximal oxygen consumption in hypoxic humans. AB - The present paper discusses the factors affecting maximal O2 consumption (VO2max) in hypoxia (4300 m above sea level) along the following lines: 1) In acute hypoxia, the fractional limitation to VO2max imposed by circulatory O2 transport (FQ') is 50%, instead of 70% as in normoxia. This is due to the increase in the blood O2 transport coefficient (beta b) as PO2 decreases, as a consequence of the sigmoidal shape of the O2 dissociation curve of hemoglobin. The remaining 50% is assumed to be equally partitioned between tissue O2 transfer (Ft') and mitochondria O2 utilization (Fm'). 2) In chronic hypoxia, FQ' = 0.45, Ft' = 0.20 and Fm' = 0.35, as a consequence of reduced muscle fiber size and muscle mitochondrial density following acclimatization. 3) The relationship between VO2max and PIO2 in both acute and chronic hypoxia reflects the O2 dissociation curve. 4) Acclimatization to chronic hypoxia does not have the function of preserving VO2max. PMID- 2253722 TI - Control of respiration in skeletal muscle at rest. AB - The suggestion is made that, under resting conditions in situ, muscle cell respiration is dependent on the way O2 and substrates are distributed to the cells by the microcirculation. (Delivery is measured as arterial-blood concentration multiplied by flow to the organ.) Microscale heterogeneity of this distribution, which is more marked but less stable than the more easily demonstrated larger-scale heterogeneity (0.1 to 0.5-g sampling grain), might indeed ration O2 and substrates in a large population of the cells of a resting organ at any given moment, and microscale heterogeneity of distribution may thus take part in the normal control of cell respiration. PMID- 2253723 TI - Role of erythropoietin in adaptation to hypoxia. AB - The glycoprotein hormone erythropoietin (EPO) counteracts tissue hypoxia by increasing the systemic oxygen-carrying capacity. It induces augmentation of red blood cell mass by stimulating the formation and differentiation of erythroid precursor cells in the bone marrow. EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the 'oxygen sensor' that controls hypoxia-induced EPO synthesis is located in the kidney itself. Within the kidneys, the local venous oxygen tension which reflects the ratio of oxygen supply to oxygen consumption is measured and transformed into a signal that regulates the formation of EPO. However, the mechanism by which a decrease of oxygen delivery to the kidneys is linked to an enhanced EPO gene expression is not yet known. Two possible mechanisms of regulation are discussed: First, renal hypoxia could lead to enhanced formation of metabolic mediators, for example prostaglandins or adenosine, which might stimulate EPO gene transcription by increasing cellular levels of second messenger molecules. Second, some kind of molecular 'oxygen receptor' such as a heme protein, that controls EPO formation by an oxygen-dependent conformational change, could mediate signal transduction. PMID- 2253724 TI - Familial Creutzfeldt-Jakob disease with temporal and spatial separation of affected members. AB - Familial occurrence of three definitive and two possible cases of Creutzfeldt Jakob disease (CJD) with temporal and spatial separation in the area of focal CJD accumulation in Slovakia is reported. Incubation period is 51 and 53 years respectively, if spatial and temporal separation of affected siblings is considered, and 51 years when the time interval between the death of the affected mother and the clinical onset in the first affected child is determined. Affected children tend to die at the same time (mean difference 3.3 years) and not at the same age (mean difference 6 years). Due to separation of the affected children, a possible common exposure to CJD infection was limited to approximately seven years during their childhood. Potential endo- and exogenous risk factors and a possible mode of CJD transmission in the described family, as well as in the CJD focus, is discussed. PMID- 2253725 TI - Considerations on a group of 13 patients with Creutzfeldt-Jakob disease in the region of Parma (Italy) AB - We report a group of 13 cases of Creutzfeldt-Jakob disease treated in the region of Parma (Italy) between 1975 and 1984. An extensive study did not point to any common source of infection. The clinical stereotypy and distinctive neuropathology in this temporo-spatially confined group of patients might be stressed, but the possibility of infection by a single strain of the CJD agent remains speculative. PMID- 2253726 TI - Incidence of occult athlete's foot in swimmers. AB - Athlete's foot is a dermatophytic infection frequently found in adults. This disease is, in some cases, asymptomatic. In order to evaluate the incidence of subclinical infection, we obtained 300 toe-web samples from the fourth interdigital space of 150 regular swimmers. More over, 66 specimens from the pool area were analysed. The method used was the carpet technique described by Mariat et al. (10). The fungal isolates were identified according to standard methods. A list of epidemiological data was completed for every swimmer. In our results, 22 swimmers had positive cultures (15%), 8 of these cases had no lesions (36%). They included 7 infections with Trichophyton mentagrophytes (87.5%) and one with T. rubrum (12.5%). We observed one case with a dual infection. Only one sample from the inanimate environment was positive. This study showed a significant incidence of occult athlete's foot in swimmers. To control this endemic problem, adequate preventive measures must be taken. PMID- 2253728 TI - Breast cancer screening in Tel Aviv. AB - Optimal breast cancer screening includes both physical examination and mammography. In anticipation of the addition of routine mammographic screening to Israel's 25-year-old early breast cancer detection program, we examined the demographic characteristics of almost one thousand women attending a breast cancer screening examination in Tel Aviv for the first time. The specific objective of the survey was to see whether women attending screening were those who stood a good chance of benefiting from it. Only half the women were aged 40 or older, and there was a preponderance of women of Western origin. Almost half had a breast-related complaint at the time of the visit. Targeted public education and appropriate administrative measures are necessary to ensure that women who can benefit from screening attend screening clinics and that clinics are not filled to capacity by women needing diagnostic evaluation and followup rather than routine screening. Tel Aviv general practitioners appeared to be aware of the advantages of breast cancer screening. PMID- 2253727 TI - Seroprevalence and risk factors for HIV transmission among female prostitutes: a community survey. AB - To estimate the prevalence of HIV-1, HIV-2 and HTLV-I among female prostitutes, and to identify possible risk factors for HIV transmission in this collective, sera and epidemiological information from 71 prostitutes were obtained. Using the local network of a well-defined area in southern Catalonia, all prostitution bars were identified and their working women interviewed using a previously validated questionnaire. Eight sera were found positive for HIV-1 antibodies. Of those, 7 sera were also positive in the HIV-2 assay, probably as a result of cross reactivity between the two viruses. All sera were negative for HTLV-I antibodies. In our area, where intravenous drug users (IVDUs) account for the majority of AIDS cases, the use of drugs by the prostitutes or by their steady sexual partners seems to be the most important risk factor for HIV infection in that group. PMID- 2253729 TI - Life expectancy in Italian track and field athletes. AB - Nine hundred eighty-three top Italian track and field athletes (700 males and 283 females) were examined for survival, mortality and causes of death for an average follow-up period of 18.6 years starting from their last year of competition as members of the national team. Overall mortality rates were compared to the rates expected on the basis of the life tables for Italian people of the same age, sex and time period. Thirty-four deaths were observed among males (vs 46.6 expected) with a O/E ratio of 0.73, while 3 deaths were observed among women (vs 6.2 expected) with a O/E ratio of 0.48. Neither of these differences was significant, but the O/E ratio for the group as a whole was quite significant (p = 0.0296). Some of the athletes demonstrated behavioural characteristics developed during their active careers that might have contributed to their low mortality rate. PMID- 2253730 TI - Dietary vitamin A, beta carotene and risk of epidermoid lung cancer in south western France. AB - This hospital-based case-control study was designed to investigate the association of low dietary vitamin A and beta carotene consumption with epidermoid lung cancer. Cases were patients with histologically confirmed epidermoid lung cancer diagnosed in six selected hospitals of southwestern France in 1983-84. Controls were selected from patients admitted to the same hospitals during the same period with diagnoses other than cancer. Cases and controls were matched for sex, age, place of residence, occupation, professional exposure to carcinogens, tobacco and alcohol consumption. A total of 106 cases of epidermoid lung cancer and 212 controls were interviewed on their typical weekly intake of 80 food items rich in preformed vitamin A and beta carotene. Index measures of the vitamin A and beta carotene daily intakes were computed for each individual patient and expressed in retinol equivalent (RE). A statistically significant odds ratio (OR) was found for preformed vitamin A (OR = 4.3; 95% CI: 2.5-7.3) with the threshold of 1,000 RE. A similar result was found for beta carotene with the same threshold (OR = 4.1; 95% CI: 2.3-7.4). Using the conditional logistic regression, consumption of preformed vitamin A and consumption of beta carotene were significantly and independently associated with epidermoid lung cancer. While confirming the protective role of beta carotene against epidermoid lung cancer, this study also shows that preformed vitamin A might have a distinct and important protective effect. PMID- 2253732 TI - The prevalence of cardiovascular risk factors among male Bedouins: a population in transition. AB - Accumulating evidence suggests that cardiovascular disease which was very rare among Negev Bedouins until the 1970's is now on the increase. The Bedouin nomads are being settled in townships and are changing habits and lifestyles as a result. The aim of this study was to determine the prevalence of known cardiovascular risk factors in Bedouins at different levels of lifestyle changes. To do so, the prevalence of the risk factors was examined in a traditional tribal group and in a settled Bedouin group. Among settled Bedouins, 15% were obese (BMI greater than 30) and a further 35% were overweight (BMI 25-29.9), as compared with no obesity and only 23% of overweight in the tribal group. The differences were most marked in the younger age group. Mean LDL-cholesterol levels also differed between the two study groups, being significantly higher in settled than in tribal Bedouins (113.9 mg% +/- SD 28.6 vs 96.9 mg% +/- SD 27.1 respectively, p less than 0.05). High BMI and LDL-cholesterol were both significantly and independently associated with being settled. No differences between the groups were found in relation to blood pressure, smoking and fasting blood glucose. It appears therefore that settlement of nomadic Bedouins and the changes associated with it, alter the pattern of cardiovascular risk factors in this population. PMID- 2253731 TI - Cardiopulmonary functional changes in acute acclimatisation to high altitude in mountaineers. AB - Simple cardiopulmonary functions were studied serially in 26 mountaineers between sea level and an altitude of 25,200 ft. Up to 12,000 ft there was no altitude sickness, though there were complaints of leech bite (26.9%) and blisters (3.8%). One member died of exhaustion, two developed pulmonary oedema, one "flu" (at 15,600 ft) and one pleural rub (at 21,000 ft). Up to 16,000 ft altitude, 4 to 7.7% developed diarrhoea or epistaxis only, but at higher levels 25 to 50% subjects developed several symptoms, besides excessive dyspnea. These included diarrhoea (35-60%), vomiting (30%) abdominal pain (35-60%), rectal bleeding (15%), chest pain (10-40%), dry cough (40-60%), giddiness (30%) and poor memory (7.7%). A small rise in blood pressure was seen (for systolic at lower and diastolic at greater altitudes). After 18,200 ft the steady increase seen in VE slowed and the rise in heart rate and respiratory rate (f) became steeper. After a small rise at 7,800 ft, FVC and FEV1 showed a gradual decline at higher altitudes. After a large initial increase in PEFR up to 12,000 ft, a gradual decline was seen. The mean weight loss during the expedition was 8 +/- 2.7 kg. These changes seem to be due to an incomplete acclimatisation, which future mountaineering teams should take into consideration to avoid health problems and improve performance. PMID- 2253733 TI - Utilization of preventive services by pregnant women in Jerusalem--a cross sectional study. AB - A study was made of health service utilization patterns during pregnancy of 279 young mothers, a representative sample of the Jewish population in Jerusalem. Only 47% reported that they used the municipal family health centers (FHCs) for prenatal care. Some 82% reported that they had resorted to more than one source of care during pregnancy. Sources other than the FHC were: regular Sick Fund doctor service (33%); private practitioners (25%); hospital-based services (25%). Among the FHC users, there was an unexpectedly high percentage of women of Asian African origin and of those living in remote neighborhoods. Under-utilization was frequent among wealthy women, those with higher education and members of the Orthodox religious sector. While there was general satisfaction with the service, lower gratification was associated with higher utilization. This phenomenon may intimate that there may be a process of negative selection among women who use the service, when other alternatives are not readily available. PMID- 2253734 TI - Circulation in Italy of beta-lactamase-producing strains within the major groups of bacterial pathogens. AB - A multicenter study was undertaken in Italy to assess the circulation of beta lactamase-producing organisms and their current incidence within the major groups of bacterial pathogens. Almost four thousand strains, all freshly isolated from clinical material, were examined at four centers serving different areas of Italy. Despite some significant center-to-center differences, this survey documented the occurrence of a large overall circulation of beta-lactamase producing organisms among clinical bacterial isolates. In particular, ampicillin resistance was recorded in one third to one half of the isolates of some Enterobacteriaceae, including Escherichia coli, Proteus, and Citrobacter species, and 80-90% of these resistant strains proved to be beta-lactamase producers. Both ampicillin resistance and beta-lactamase production were almost the rule in other Enterobacteriaceae, including Klebsiella, Enterobacter, and Serratia species. beta-lactamase was also produced by about 80% of glucose-non-fermenting gram negative bacteria and Aeromonas hydrophila strains, by all of the isolates of Branhamella catarrhalis manifesting ampicillin resistance (i.e. more than half the total number of isolates), and by about two thirds of the ampicillin resistant Haemophilus strains (which accounted for 20-25% of all Haemophilus isolates examined). In contrast, no beta-lactamase producers were observed among Neisseria gonorrhoeae isolates. PMID- 2253735 TI - Laboratory survey of Chlamydia trachomatis ocular infections. AB - The authors used immunofluorescence and immunoperoxidase tests to study a group of 101 patients with acute or chronic conjunctivitis, etiologically unrelated to conventional bacterial pathogens, and a control group of 30 healthy adults. Positive titers of IgG in serum and of IgA in lacrimal secretions against Chlamydia, detected by IPA, correlated with the identification of microorganisms by direct immunofluorescence. The use of both tests allows a precise evaluation of the stage of the infection and of its evolutive pattern. PMID- 2253736 TI - Public health application of a serological test for tuberculosis: study of the incidence of inapparent infections among the employees of an Alsatian supermarket. AB - A serodiagnostic test based on antigen 60 has been used to analyse the presence of IgG antibodies specific for mycobacteria, in the serum of the employees of a food supermarket. More than fourteen percent of the employees were seropositive, compared to 1.5% in a health adult population. The seropositives were restricted to those employees who were in direct contact with the customers. PMID- 2253737 TI - Seroprevalence of anti-Chlamydia trachomatis IgG in outpatients attending a sexually transmitted disease clinic in Italy. AB - Prevalence of anti-Chlamydia trachomatis specific IgG antibodies was evaluated in a sexually transmitted disease outpatient population composed of 741 heterosexuals, 470 males and 271 females, and of 147 homosexual-bisexual men. The prevalence rates were 60.0% in heterosexual males, 50.6% in females and 73.5% in homosexuals-bisexuals. A positive association between age and antibody prevalence was found in males. Among heterosexuals there is an increasing trend of seropositivity with number of partners during the previous year. A significant association between anti-chlamydial and anti-herpes simplex, type 2, antibodies has been demonstrated. PMID- 2253738 TI - Parallelism in the mortality clustering of the most frequent cancer sites in Italy and in the Marche region. AB - Clusters of selected cancer sites mortality, regarding Italy and the Marche region, were compared. Very similar associations were found both in males and in females, in particular between the alcohol-tobacco-related sites. Many clusters agree with the international literature, while others could constitute a starting point for formulating new hypotheses. PMID- 2253740 TI - HIV transmission by fellatio. PMID- 2253739 TI - Chlamydia trachomatis infection in primary unexplained infertility. AB - In recent years Chlamydia trachomatis has emerged as a significant cause of acute salpingitis and reproductory failure. In this study, 85 women suffering from primary infertility and 85 parous women as control group were screened for C. trachomatis genital infection by means of cell culture and antigen detection on genital samples as well as the detection of anti-chlamydial antibodies in blood. C. trachomatis was detected in 31.8% of infertile women and 5.8% of fertile subjects. Isolation of C. trachomatis in cell culture proved to be the most reliable diagnostic tool when compared to immunofluorescence staining on smears and serology. Although the latter may be considered of great value in epidemiological researches, culture isolation should be associated for the diagnosis of active infection. PMID- 2253741 TI - [The neurochemical characteristics of the effect of morphine and pentapeptide FK 33-824 on cerebral cortical excitability]. AB - GABA-stimulating agents (muscimol, depakine, aminohydroxyacetic acid), serotonin stimulants (5-hydroxytryptophan, fluoxetine), catecholaminergic stimulants (L DOPA, apomorphine) and a cholinergic inhibitor (hemicholinium-3) of the brain were found to enhance the inhibitory effect of morphine and pentapeptide FK 33 824 on the cortical excitability of free-moving cats. GABA-negative agents (thiosemicarbazide, bicuculline, picrotoxin), serotonin-negative agents (p chlorophenylalanine, methysergide), catecholaminergic inhibitors (6 hydroxydopamine, alpha-methyl-p-tyrosine) and cholinergic stimulant (physostigmine) of the brain appeared to decrease the effects of morphine and pentapeptide FK 33-824 on the excitability of the cortex. beta-adrenoceptor blocker propranolol decreased the effects of morphine and pentapeptide FK 33-824 on the cortical excitability, whereas alpha-adrenoblockers (phentolamine, phenoxybenzamine and yochimbine) exerted no effect on their action. PMID- 2253742 TI - [The effect of dexamethasone on the orientation and exploratory activity and the amino acid composition in different CNS structures of rats in experimental neurosis]. AB - The effect of dexamethasone (50 mg/kg, intraperitoneally, 24 hours before the experiment) on the orientation activity of the rats in the "open field" was studied in experimental neurosis. The formation of neurosis was accompanied by changes in the locomotor and orientation activities, amino acid concentrations in the brain structures. This manifested itself in an increase of GABA amounts in the frontal cortex, hippocampus and striatum by 56, 29 and 27%, respectively (p less than 0.001, 0.05 and 0.001). In the subcortical structures the contents of glutamic acid increased and the amounts of phenylalanine decreased. Dexamethasone was found to enhance the orientation activity and to change the neurochemical organization of the brain structures, to a greater extent in the hippocampus, that manifested itself in a sharp decrease of the contents of neuroactive amino acids. PMID- 2253743 TI - [The effect of mildronate on disorders of the cardiac contractile function in rats caused by an excess of free fatty acids and ischemia]. AB - Oral administration of mildronate, 3-(2,2,2-trimethylhydrazine)propionate, an inhibitor of carnitine-dependent metabolism, in a dose of 50-100 mg/kg for 10 days promoted a rapid restoration of contractility of Langendorf perfused rat heart preparations during postischemic perfusion and protected the rat hearts against inhibition of contractile function resulting from continuous perfusion with palmitic acid. Mildronate inhibits gamma-butyrobetaine hydroxylase, depresses carnitine biosynthesis and reduces carnitine-dependent fatty acid metabolism. The cardioprotective effect of mildronate is particularly manifest upon continuous administration. PMID- 2253744 TI - [Changes in the effects of verapamil in sensitized dogs]. AB - The cardiovascular effects of verapamil were studied on anesthetized dogs with the intact chest, control ones and those sensitized with horse serum. Verapamil dose inducing the minimal cardio- and hemodynamic effects in the sensitized dogs was 2-3 times less that used in the controls. In addition, in contrast to the control dogs, the sensitized dogs exhibited the cardiotoxic effects of verapamil a disorder of atrioventricular conductivity and a deterioration of the cardiac muscle relaxation. The cardiovascular effects of verapamil are modified by sensitization of the organism by heterologous serum proteins. PMID- 2253745 TI - [An analysis of the cardiovascular reactions due to mebikar]. AB - The effect of a tranquillizer mebicar on the cardiovascular system was studied experimentally. The drug was shown to increase the myocardial contractility, to exert a slight effect on the cardiac rhythm, to dilate the peripheral arteries. The analysis revealed that the vasodilating properties of mebicar are related to its central neurotropic action. The cardiac stimulating effects depend on the involvement of mebicar in the myocardial metabolism. PMID- 2253746 TI - [A comparative study of the toxic and therapeutic effects of digoxin and its immobilized form]. AB - It was shown on different species of laboratory animals (frogs, mice, rats) that digoxin immobilized on the copolymer was 8-15 times less toxic that its usual preparation. In this case glycoside fixed on the copolymer preserves completely its specific cardiotonic effect, i.e., possesses a wider range of the therapeutic action. PMID- 2253747 TI - [A comparative study of the pharmacokinetics of oral preparations of theophylline]. AB - The pharmacokinetics of five preparations of theophylline--euphylline and sustained-release forms (theo-dura, retaphylline, theopac and theobilong) was studied in 50 patients with the broncho-obstructive syndrome. Blood serum theophylline concentration was determined by high performance liquid chromatography. The main differences in the pharmacokinetic parameters manifested themselves in the period of half-absorption--the least one for euphylline and the greatest one for theopac. A close correlation between blood serum theophylline concentration and the profile of theophylline release from theopac tablets was revealed. The equal theophylline concentration in blood serum was determined on the 4th and 7th days of the course treatment with sustained-release preparations administered twice a day, the concentration values ranged within the subtherapeutic level. An increase of the dose by 50-150 mg/day resulted in an increase of blood serum theophylline concentration within the therapeutic range. PMID- 2253748 TI - [The effect of eplir on an experimental toxic lesion of the liver]. AB - A hepatoprotector of phospholipid nature eplir extracted from silt mud was shown to prevent like essentiale in CCl4-hepatitis in rats the development of the liver parenchyma necroses, to promote the maintenance of the normal activity of enzymes in hepatocytes, to stabilize lysosomes, to stimulate the antitoxic and excretory functions of the liver, to reduce hyperfermentemia. The mechanism of action of eplir is determined by the antioxidant properties, a decrease of lysophosphatide formation and the inclusion of phosphatidylcholine in membranes. PMID- 2253749 TI - [Comparison of the antioxidative activity of fenibut, fentolamin and ionol]. AB - Phenibut and phentolamine were found to exhibit the properties of the true antioxidants in the hen egg yolk suspension and in the rat brain homogenate. The antioxidative activities of the drugs were significantly higher in the brain homogenate, while the antioxidative activity of the known antioxidant ionol was unchanged. PMID- 2253750 TI - [Condition of cell membranes in simulated motion sickness and use of alpha tocopherol]. AB - The purpose of the work was to study the mechanism responsible for adaptive reorganization of membranes--lipid peroxidation during simulated motion sickness (MS) in animals. It was shown that during MS rats exhibited an elevation of the level of diene conjugates and Schiff foundations in the brain indicating lipid peroxidation activation. A similar increase of phospholipase A2 activity in the brain was noted. In the liver, myocardium and erythrocytes the above changes were insignificant. An antioxidant beta-tocopherol inhibited lipid peroxidation in the rat brain and possessed the vestibule-protective effect in cats that was presumably related to its membrane-stabilizing action. PMID- 2253751 TI - [The role of microsomal oxidation processes in the development of haloperidol tolerance during melatonin administration and epiphysectomy in rats]. AB - A pineal hormone melatonin (1 mg/kg, 24 days) facilitated the formation of tolerance to haloperidol and eliminated the changes produced by it in the processes of microsomal oxidation in rats. Pinealectomy yielded the opposite result. After pinealectomy the normalizing effect of the hormone on the condition of the liver monoxygenase system and the effects of haloperidol weakened. PMID- 2253752 TI - [The effect of the complex platinum (IV) compound oxoplatinum on the immune system]. AB - The effect of a Pt (IV) complex compound--oxoplatinum on the humoral and cell immunity in mice was studied. It was established that the drug produced dose dependent inhibition of T-dependent humoral response to ram erythrocytes. Oxoplatinum appeared to be a costimulator of a mitogen phytohemagglutinin in lymphocyte proliferation slightly influencing allogen-induced proliferation. The stimulation of T-lymphocyte cytotoxicity by small doses of oxoplatinum was also found. PMID- 2253753 TI - [The relationship between antipyrine kinetics and the change in the seromucoid content of rat plasma under the influence of the immunomodulator levamisole]. AB - The relationship between levamisole-induced changes in seromucoid levels and drug metabolism was studied. In the single dose study rats received levamisole hydrochloride (25 mg/kg by gastric intubation 24 hours before antipyrine administration in a dose of 10 mg/rat intravenously). This resulted in a decrease of antipyrine clearance and an increase of half-life. In contrast, the multiple administrations (5 mg/kg for 2 days in a week for 3 weeks) had no significant effect on the pharmacokinetics of antipyrine. However, in both cases seromucoid levels were elevated. It is concluded that the research on the effect of levamisole on drug metabolism and drug binding to plasma proteins in man is needed. PMID- 2253755 TI - [The effect of neurotropic agents on the development of toxic brain edema in sexually immature animals]. AB - It was established on two age groups of rats that toxic brain edema in one-month old animals is prevented by dopegit (100 mg/kg) and aminazine (2.5 mg/kg). The pharmacological correction of the brain edema in two-month-old rats is similar to that in adult animals. The central adrenergic structures play the significant role in the development of the brain edema in sexually immature animals. PMID- 2253754 TI - [The characteristics of the enzyme status of the antioxidant protection and the level of lipid peroxidation in the brain tissue and blood of rats with differing preferences for ethanol]. AB - The ethanol-preferring (EP) rats have a higher level of lipid peroxidation in the brain and blood serum than the water-preferring rats. At the same time it was found that EP rats have a decreased antioxidant enzyme activity in the brain tissue (catalase and superoxide dismutase) and blood serum (ceruloplasmin and superoxide dismutase). This antioxidant status can lead to a greater sensitivity of the EP rat brain to ethanol toxicity. The increased catalase activity in blood of EP rats reflects the elevated metabolic tolerance of this group of animals to ethanol. PMID- 2253756 TI - [The effect of millet oil on the regeneration process in trophic ulcers]. AB - The effect of the local use of Oleum Miliacei on the regenerative processes of trophic ulcers was studied for the first time on 74 rabbits. Oleum Miliacei is obtained from millet scraps, a by-product of groat processing. The experiments confirmed that Oleum Miliacei has the anti-inflammatory action and stimulates the processes of regeneration. Its higher healing effects as compared with Oleum Hippophae and Oleum Rosae was shown. It precipitated ulcer healing as compared with the latter preparations. PMID- 2253757 TI - [Temporal dynamics of forced swimming in rats as an adequate criterion for assessing the specific effects of antidepressants]. AB - Rats with different rhythmical structure of forced swimming had different susceptibility to antidepressant drugs. The drugs equally changed only the rhythmical index of depression but not other swimming parameters in sensible animals. As suggested, the assessment of swimming time-course can be used for antidepressant screening and preliminary selection of drug-resistant animals. PMID- 2253758 TI - [The use of 2-component myocardial contraction for assessing the mechanism of action of inotropic substances]. AB - The possibility of using two-component contraction of the myocardium to evaluate the mechanisms of action of cardiotropic pharmacological agents was studied. Caffeine, ouabain, low-natrium solution, varapamil, nifedipine and BAY K-8644 were used. It was concluded that the analysis of contraction component amplitude dynamics makes it possible to determine the effect of the pharmacological agents on the interrelated mechanisms of the delivery of Ca2+ into the myoplasm of cardiomyocytes from sarcoplasmic reticulum and through sarcolemma during a single cardiac cycle. PMID- 2253759 TI - [The pharmacologic and biochemical effects of unsaturated phospholipids]. AB - The review deals with the analysis of the recent publications indicating the important biological function of essential phospholopids (EP) in the cell and in the organism as a whole. The protective mechanism of action of EP in diseases of the liver, atherosclerosis, ischemic heart disease, myocardial infarction determined by their high biological activity in some pathological conditions associated with lipid metabolism disturbance is discussed. The efficiency of the biological action of EP is determined by the depends on the type of phospholipids, the form of phospholipid preparations, their charge, and also on the routes of their administration. PMID- 2253760 TI - [The clinical pharmacology of antiepileptic agents]. AB - The correct choice of an antiepileptic drug, its individual dosage and schedule of administration at the beginning of treatment and then during the maintenance therapy promotes a complete control of seizures using one anticonvulsant in 60 90% of patients. The treatment should be initiated with administration of one drug which is adequate for the given type of seizures taking into consideration that different drugs can appear effective in different patients with the same form of epilepsy. One has to choose drugs by consecutively gradually changing them. The optimization of epilepsy treatment should be performed on the basis of the knowledge of the clinicopharmacological characteristic of the main antiepileptic drugs described in the lecture. PMID- 2253761 TI - Mechanism of the neurotoxicity of MPTP. An update. AB - This review summarizes advances in our understanding of the biochemical events which underlie the remarkable neurotoxic action of MPTP (1-methyl-4-phenyl-1 1,2,3,6-tetrahydropyridine) and the parkinsonian symptoms it causes in primates. The initial biochemical event is a two-step oxidation by monoamine oxidase B in glial cells to MPP+ (1-methyl-4-phenylpyridinium). A large number of MPTP analogs substituted in the aromatic (but not in the pyridine) ring are also oxidized by monoamine oxidase A or B, is in some cases faster than any previously recognized substrate. Alkyl substitution at the 2'-position changes MPTP, a predominantly B type substrate, to an A substrate. Following concentration in the dopamine neurons by the synaptic system, which has a high affinity for the carrier, MPP+ and its positively charged neurotoxic analogs are further concentrated by the electrical gradient of the inner membrane and then more slowly penetrate the hydrophobic reaction site on NADH dehydrogenase. Both of the latter events are accelerated by the tetraphenylboron anion, which forms ion pairs with MPP+ and its analogs. Mitochondrial damage is now widely accepted as the primary cause of the MPTP induced death of the nigrostriatal cells. The molecular target of MPP+, its neurotoxic product, is NADH dehydrogenase. Recent experiments suggest that the binding site is at or near the combining site of the classical respiratory inhibitors, rotenone and piericidin A. PMID- 2253762 TI - Quantitative measurements on the duplex stability of 2,6-diaminopurine and 5 chloro-uracil nucleotides using enzymatically synthesized oligomers. AB - 2,6-Diaminopurine and 5-chloro-uracil 2'-deoxynucleoside 5'-triphosphates were synthesized from their 2'-deoxynucleosides. Using a method of creating oligonucleotides by enzymatic primer extension, dodecanucleotides representing an XbaI/SalI site and the complementary SalI/XbaI site were generated containing these base modifications. Their duplex stability was quantitatively compared by thin-layer chromatography to oligomers containing 2'-deoxyadenosine and 2' deoxythymidine. The two unmodified oligomers already showed significant differences in dissociation temperature and binding equilibrium. Substitution with 5-chloro-2'-deoxyuridine did not affect the dissociation temperature of either oligomer, the 2,6-diaminopurine, however, led to an increase of 1.8 degrees C or 1.5 degrees C per modified base, respectively. While in the XbaI/SalI oligomer both base modifications changed the binding equilibrium, the 2,6-diaminopurine by a factor of 1.32, the 5-chloro-uracil by 0.65, no such effect was found with the complementary oligomer. PMID- 2253763 TI - Mechanism of inhibition of lipid peroxidation by tamoxifen and 4-hydroxytamoxifen introduced into liposomes. Similarity to cholesterol and ergosterol. AB - The anticancer drug tamoxifen when introduced into phospholipid liposomes during their preparation inhibited Fe(III)-ascorbate induced lipid peroxidation to a greater extent than similarly introduced cholesterol. Ergosterol was equipotent with tamoxifen, but much less effective than 4-hydroxytamoxifen. Possible mechanisms underlying these effects are discussed in relation to structural mimicry of the sterols by these triphenylethylene drugs as membrane stabilizers against lipid peroxidation. PMID- 2253764 TI - Thiol-fatty acylation of the glucose transport protein of human erythrocytes. AB - Incubation of intact human erythrocytes with [3H]palmitate labeled a protein with electrophoretic characteristics of the glucose transporter. This labeling occurred via a thioester linkage, since it was unaffected by organic solvent extraction, but was substantially removed as the hydroxamate upon treatment with neutral hydroxylamine. Immunoprecipitation of the labeled protein with a monoclonal antibody to the glucose transporter confirmed its identity. PMID- 2253765 TI - Comparison of phosphorylation of elongation factor 1 from different species by casein kinase II. AB - One subunit of EF-1 or EF-1 beta gamma from Artemia salina, wheat germ and rabbit reticulocytes is modified by casein kinase II. The subunit corresponds to the low Mr subunit of EF-1 (26,000-36,000) which functions along with a higher Mr subunit (46,000-48,000), to catalyze the exchange of GDP for GTP on EF-1 alpha. The factor from Artemia and wheat germ is phosphorylated directly on serine by casein kinase II whereas a modulatory compound is required for phosphorylation of EF-1 from reticulocytes. Polylysine increases the rate of phosphorylation of EF-1 from reticulocytes by 24-fold; both serine and threonine are modified. This suggests that polylysine may be substituting for a physiological regulatory compound which modulates phosphorylation in vivo. PMID- 2253766 TI - Isolation and sequence of a tropomyosin-binding fragment of turkey gizzard calponin. AB - Limited chymotryptic cleavage of turkey gizzard calponin yields a 13 kDa fragment which could be purified by its ability to bind to Sepharose-immobilized tropomyosin. This 13 kD polypeptide is shown to be derived from a 22 kDa fragment. Complete amino acid sequence analysis of the 13 kD and 22 kD fragments reveals high homology with the formerly characterized smooth muscle-specific protein SM22 alpha (Pearlstone, J.R., Weber, M., Lees-Miller, J.P., Carpenter, M.R. and Smillie L.B., 1987, J. Biol. Chem. 262, 5985-5991) and the product of gene mp20 of Drosophila (Ayme-Southqate, A., Lasko, P., French, C, and Pardue, M.L. [(1989) J. Cell Biol. 108, 521-531]. Futhermore we recognize sequence elements of a putative actin-binding domain of alpha-actinin, the calpactin I or p 36 sequence, and a consensus motif present in the repeats of the gene product of the candidate unc-87 gene of C. elegans (S.D. Goetinck and R.H. Waterston, personal communication). PMID- 2253767 TI - Polyphosphate-hydrolysis--a protective mechanism against alkaline stress? AB - Different microorganisms, including yeast and algae, accumulate large amounts of polyphosphates. However, the physiological role of polyphosphates is largely unknown. In vivo 31P NMR studies, carried out in the unicellular alga, Dunaliella salina, demonstrate the cytoplasmic alkalization induces massive hydrolysis of polyphosphates, which is correlated kinetically with the recovery of cytoplasmic pH. Analysis of acid extracts of the cells indicates that long-chain polyphosphates are hydrolysed mainly to tripolyphosphate. It is suggested that the hydrolysis of polyphosphates provides a pH-stat mechanism to counterbalance alkaline stress. PMID- 2253769 TI - Smooth muscle specific expression of calponin. AB - Calponin is an actin-, calmodulin-, and tropomyosin-binding protein that has been isolated from smooth muscle tissue. Using a monoclonal antibody specific for avian calponin, we demonstrate a differentiation-linked increase in calponin expression in embryonic chick gizzard. Cultivation of gizzard smooth muscle cells in vitro resulted in a down-regulation of calponin expression after the first 48 h that was paralleled by a loss of synthesis of metavinculin and the high molecular weight isoform of caldesmon. In early cultures of smooth muscle cells calponin was localised in the actin-containing stress fibres but labelling was restricted to the central parts of the actin cytoskeleton. Calponin expression is suggested as a potentially useful index of smooth muscle differentiation. PMID- 2253770 TI - Estimation of flux control coefficients from inhibitor titrations by non-linear regression. AB - A mathematical model was developed to estimate flux control coefficients (Co) from titration studies with specific non-competitive inhibitors. In contrast to the normally used graphical determination the model pays regard to the dissociation equilibrium (KD) that exists between inhibitor and its binding sites (Eo) as well as to an objective estimation of the initial slope. The model was used for the analysis of titration experiments where the respiration of rat liver mitochondria was inhibited with carboxyatractyloside and antimycin A. It is shown that the graphical estimation of Eo and Co lead to significant overestimation if the ratio KD/Eo is larger than 10(-4) which can be avoided by using our model. PMID- 2253768 TI - All-D-magainin: chirality, antimicrobial activity and proteolytic resistance. AB - All-D-magainin-2 was synthesized to corroborate experimentally the notion that the biological function of a surface-active peptide stems primarily from its unique amphiphilic alpha-helical structure. Indeed, the peptide exhibited antibacterial potency nearly identical to that of the all-L-enantiomer. Being highly resistant to proteolysis and non-hemolytic all-D-magainin might have considerable therapeutic importance. PMID- 2253771 TI - Unique property of liver mitochondrial P450 to catalyze the two physiologically important reactions involved in both cholesterol catabolism and vitamin D activation. AB - The cDNA for vitamin D 25-hydroxylase in rat liver mitochondria was transfected in COS cells in order to confirm our previous postulation that both 5 beta cholestane-3 alpha, 7 alpha, 12 alpha-triol 27-hydroxylation and vitamin D 25 hydroxylation are catalyzed by a common enzyme. As a result it was found that both enzyme activities could be reconstituted from the solubilized extract of mitochondria of these cells, NADPH, NADPH-adrenodoxin reductase and adrenodoxin, giving unequivocal evidence that the two enzyme activities are catalyzed by a common enzyme. PMID- 2253772 TI - Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3. AB - Overlapping cDNAs encoding human platelet glycoprotein (Gp)IX were cloned from a human erythroleukemia cell lambda gt11 library. The possibly 'full-length' cDNA of 896 base pairs (bp) includes an open reading frame (528 bp), both 5' (222 bp) and 3' (146 bp) noncoding regions, and a poly(A) tail. Translation predicts a signal peptide of 16 amino acids and a mature protein of 160 amino acids that includes a 24 amino acid leucine-rich glycoprotein (LRG) segment. Southern blot analysis suggests the presence of a single copy of the Gp IX gene, and hybridization of Gp IX cDNA to sorted human chromosomes localizes the Gp IX gene to chromosome 3. PMID- 2253773 TI - The stereochemical requirement for protein kinase C activation by 3 methyldiglycerides matches that found in naturally occurring tumor promoters aplysiatoxins. AB - Protein kinase C is stereospecifically activated by sn-1,2-(S)-diglycerides. A second chiral center was introduced into the diglycerides by preparing the 3 methyl derivatives. The activation of protein kinase C was also stereospecific with respect to the new chiral center established at the C3 position of the methylated diglycerides. The stereospecifically of protein kinase C directed towards the C2 and C3 positions of the diglycerides is matched in the analogous C29 and C30 stereocenters of the tumor promoting debromoaplysiatoxins. This finding strengthens the view that the structurally diverse tumor promotors contain the embedded diglyceride-like pharmacophore. PMID- 2253774 TI - 2,5-Di-(tert-butyl)-1,4-benzohydroquinone mobilizes inositol 1,4,5-trisphosphate sensitive and -insensitive Ca2+ stores. AB - In permeabilized rat hepatocytes a maximal concentration (25 microM) of 2,5-di (tert-butyl)-1,4-benzohydroquineone (tBuBHQ) mobilized 70% of sequestere Ca2+ and a half-maximal effect was produced by 1.7 microM tBuBHQ. Inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) stimulated release of about 40% of the intracellular Ca2+ stores. Combined applications of a range of tBuBHQ concentrations with a maximal concentration of Ins(1,4,5)P3 demonstrated that tBuBHQ has slight selectivity for the Ca2+ transport process of the Ins(1,4,5)P3-sensitive stores. We conclude that the Ins(1,4,5)P3-sensitive stores are a subset of those sensitive to tBuBHQ and that the latter is therefore unlikely to prove useful as a tool to discriminate Ins(1,4,5)P3-sensitive and -insensitive Ca2+ stores though it may provide opportunities to design more selective agents. PMID- 2253775 TI - Computer simulation of zinc finger motifs from cellular nucleic acid binding protein and their interaction with consensus DNA sequences. AB - We report here a computer simulation of the three-dimensional structures of seven zinc finger motifs from cellular nucleic acid binding protein involved in negative feedback inhibition of cholesterol biosynthesis. The structures are optimised using steric constraints imposed by tetrahedral coordination of the zinc ion with Cys and His residues, by molecular mechanics technique. We have also optimised the structure of a finger-I with GpT sequence. The model for the interaction of seven fingered protein with single-stranded d(GTGCGGTG) from sterol regulatory element (SRE) is given on the basis of these results. We also propose a scheme for recognition of a multifingered regulatory protein with small single-stranded DNA fragments. PMID- 2253776 TI - Firefly luciferase, synthesized to very high levels in caterpillars infected with a recombinant baculovirus, can also be used as an efficient reporter enzyme in vivo. AB - Trichoplusia ni and Spodoptera littoralis larvae were infected with a recombinant AcNPV, having the viral polyhedrin gene replaced with the cDNA encoding firefly luciferase. Both S. littoralis and T. ni synthesized very high levels of luciferase representing greater than or equal to 25% and greater than or equal to 15%, respectively of the total Coomassie blue stainable protein. Luciferase was apparently not secreted into the hemolymph but was contained within the body tissue. Expression in S. littoralis larvae suggests that luciferase can be an excellent reporter enzyme to study virus infection, dissemination and expression in different tissues, host range determination, insect physiology and also to monitor the release of recombinant virus in the environment when used as a biocide. PMID- 2253777 TI - A new form of baker's yeast transketolase. An enzyme-RNA complex. AB - Using an immunosorbent, a new form of transketolase, namely, an enzyme-RNA complex, was isolated from a baker's yeast extract. Spontaneous fission of RNA (or its enzymic hydrolysis by RNase) is accompanied by a sharp increase in the catalytic activity of transketolase, which may be directly related to the enzyme's regulation mechanism. PMID- 2253778 TI - Involvement of thymosin beta 4 and endoproteinase Asp-N in the biosynthesis of the tetrapeptide AcSerAspLysPro a regulator of the hematopoietic system. AB - It is shown that AcSDKP a new regulator of the hematopoietic system can be generated from thymosin beta 4 by a one-step enzymatic cleavage in vitro and in vivo. AcSDKP and T beta 4 were both detected in bone marrow cells (BMC). Incubation of [3H]T beta 4 with either intact or lysed BMC led to the formation of [3H]AcSDKP whereas the labelled tetrapeptide was not degraded under these conditions. Model enzymatic degradation of T beta 4 carried out with bacterial enzymes suggests that a mammalian endoproteinase Asp-N might be involved in the formation of AcSDKP through the specific cleavage of the 4Pro-5 Asp peptide bond of T beta 4. PMID- 2253780 TI - Protonated triplex DNA in E. coli cells as detected by chemical probing. AB - The triplex structure in vitro is well established; however, no direct evidence has been available concerning its existence in the cell. Using the direct chemical probing here we show that the triplex H structure can exist in E. coli cells at acidic intracellular pH values; this structure differs in some details from that observed in vitro. PMID- 2253779 TI - Effects of cycloheximide and tunicamycin on cell surface expression of pancreatic muscarinic acetylcholine receptors. AB - The importance of glycosylation in cell surface expression of muscarinic receptors in cultured guinea pig pancreatic acini was investigated. Recovery of the muscarinic receptor population after carbachol-induced down regulation was blocked by cycloheximide but not by tunicamycin, although tunicamycin reduced [3H]mannose incorporation into acinar macromolecules by up to 90%. Tunicamycin treatment also failed to alter carbachol stimulation of amylase secretion from cultured acini. These results indicate that glycosylation of the glandular subtype of muscarinic receptor in the pancreatic acinar cell is not necessary for its insertion in the plasma membrane or for its functional activity. PMID- 2253781 TI - A new small myotoxin from the venom of the prairie rattlesnake (Crotalus viridis viridis). AB - Fast atom bombardment (FAB) mass spectrometry was used to identify a new small myotoxin from the venom of the prairie rattlesnake (Crotalus viridis viridis). FAB mass spectrometry and Edman degradation were used to characterize its structure. This toxin is similar to myotoxin I from C. v. concolor, except that it possesses an additional. C-terminal asparaginyl-alanine. At 45 residues it is the longest known myotoxin a homolog. A myotoxin of 43 residues, identical to myotoxin I from C. v. concolor, was also found. To date no other species has been shown to produce more than one length of myotoxin. The present paper documents 42 , 43-, and 45-residue myotoxins from the venom of a single animal. PMID- 2253783 TI - Crystal structure of an alkaline protease from Bacillus alcalophilus at 2.4 A resolution. AB - The crystal structure of an alkaline protease from Bacillus alcalophilus has been determined by X-ray diffraction at 2.4 A resolution. The enzyme crystallizes in space group P2(1)2(1)2(1) with lattice constants a = 53.7, b = 61.6, c = 75.9 A. The structure was solved by molecular replacement using the structure of subtilisin Carlsberg as search model. Refinement using molecular dynamics and restrained least squares methods results in a crystallographic R-factor of 0.185. The tertiary structure is very similar to that of subtilisin Carlsberg. The greatest structural differences occur in loops at the surface of the protein. PMID- 2253782 TI - The molybdenum cofactor of formylmethanofuran dehydrogenase from Methanosarcina barkeri is a molybdopterin guanine dinucleotide. AB - The molybdenum cofactor of formylmethanofuran dehydrogenase from methanol-grown Methanosarcina barkeri was isolated as the [di(carboxamidomethyl)]-derivative. The alkylated factor showed an absorption spectrum and chemical properties identical to those recently reported for the molybdenum cofactor of dimethyl sulfoxide reductase from Rhodobacter sphaeroides. By treatment with nucleotide pyrophosphatase the factor was resolved into two components, which were identified as [di(carboxamidomethyl)]-molybdopterin and GMP by their absorption spectra, their retention times on Lichrospher RP-18, and by their conversion to dephospho-[di(carboxamidomethyl)]-molybdopterin and guanosine, respectively, in the presence of alkaline phosphatase. The GMP-moiety was sensitive to periodate, identifying it as the 5'-isomer. These results demonstrate that the molybdenum cofactor isolated from formylmethanofuran dehydrogenase contains the phosphoric anhydride of molybdopterin and 5'-GMP. PMID- 2253784 TI - Immunocharacterization of beta- and zeta-subspecies of protein kinase C in bovine neutrophils. AB - The isoforms present in a crude preparation of bovine neutrophil protein kinase (PKC) were identified by immunodetection with antibodies directed against specific sequences of bovine and rat brain PKC isozymes. The major isoform of bovine neutrophil PKC was identified as beta-PKC and the minor one as zeta-PKC. PMID- 2253785 TI - The Na(+)-independent Ca2+ efflux system in mitochondria is a Ca2+/2H+ exchange system. AB - The mechanism of the Na(+)-independent Ca2+ efflux system in mitochondria has not been elucidated as yet. With the aid of cyclosporin A, an inhibitor of the Ca2(+) induced 'pore', and using a variety of inhibitors, uncouplers and ionophores, it is possible to demonstrate, unequivocally, that this process is driven by delta pH. The efflux is not affected by delta psi, thus suggesting an electroneutral Ca2+/2H+ exchange mechanism. Parallel measurements of the rate of Ca2+ efflux and delta pH, as modulated by valinomycin and nigericin, indicate that the rate of efflux is a function of the magnitude of delta pH. PMID- 2253787 TI - Lack of conversion of xanthine dehydrogenase to xanthine oxidase during warm renal ischemia. AB - Irreversible transformation of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) during ischemia was determined measuring XDH and total enzyme activity in kidneys before and after 60 min of clamp of the renal pedicle. Tissue levels of adenine nucleotides, xanthine and hypoxanthine were used as indicators of ischemia. After 60 min of clamping, ATP levels decreased by 72% with respect to controls whereas xanthine and hypoxanthine progressively reached tissue concentrations of 732 +/- 49 and 979 +/- 15 nmol.g tissue-1, respectively. Both total and XDH activities in ischemic kidneys (30 +/- 15 and 19 +/- 1 nmol.min-1.g tissue-1) were significantly lower than in controls when expressed on a tissue weight basis. The fraction of enzyme in the XDH form was however unchanged indicating that the reduction of the nucleotide pool is not accompanied by induction of the type-O activity of xanthine oxidase. PMID- 2253786 TI - Protein synthesis is required for the denervation-triggered activation of acetylcholine receptor genes. AB - The effect of cycloheximide (CHX) on denervation-induced acetylcholine receptor (AChR) expression was investigated in chickens one day after nerve section, using probe excess solution hybridization to quantitate AChR alpha-subunit gene transcript levels and run-on analysis to measure subunit gene activity. The increase in alpha-subunit transcripts that normally follows denervation was prevented when drug treatment was commenced 2 h before or after denervation but was not blocked when CHX administration was begun 6 h after the operation. Drug induced reduction of transcript levels results from decreased activity of genes coding for the alpha-, delta-, and gamma-subunits; in contrast, the transcription rates of several non-receptor genes are not affected by CHX. The results suggest that the de novo synthesis of a transcriptional activator is required as a mediating event in the signalling pathway linking the plasma membrane and AChR gene expression. PMID- 2253788 TI - In vivo evidence for FhuA outer membrane receptor interaction with the TonB inner membrane protein of Escherichia coli. AB - FhuA outer membrane receptor activity of Escherichia coli K-12 depends on the TonB inner membrane protein. The naturally occurring degradation of the TonB protein could be prevented by the FhuA receptor protein. Mutated TonB proteins could only be stabilized by mutated FhuA proteins when they functionally interacted in the uptake of ferrichrome across the outer membrane. PMID- 2253789 TI - Distribution of lecithin-retinol acyltransferase activity in different types of rat liver cells and subcellular fractions. AB - It is now well documented that lecithin-retinol acyltransferase (LRAT) is the physiologically important enzyme activity involved in the esterification of retinol in the liver. However, no information regarding the cellular distribution of this enzyme in the liver is presently available. This study characterizes the distribution of LRAT activity in the different types of rat liver cells. Purified preparations of isolated parenchymal, fat-storing, and Kupffer + endothelial cells were isolated from rat livers and the LRAT activity present in microsomes prepared from each of these cell fractions was determined. The fat-storing cells were found to contain the highest level of LRAT specific activity (383 +/- 54 pmol retinyl ester formed min-1.mg-1 versus 163 +/- 22 pmol retinyl ester formed min-1.mg-1 for whole liver microsomes). The level of LRAT specific activity in parenchymal cell microsomes (158 +/- 53 pmol retinyl ester formed min-1.mg-1) was very similar to LRAT levels in whole liver microsomes. The Kuppfer + endothelial cell microsome fractions were found to contain LRAT, at low levels of activity. These results indicate that the fat-storing cells are very enriched in LRAT but the parenchymal cells also posses significant levels of LRAT activity. PMID- 2253790 TI - Two naturally-occurring isoforms and their expression of a glucocorticoid receptor gene from an androgen-dependent mouse tumor. AB - We have isolated cDNAs encoding the glucocorticoid receptor from an androgen dependent mouse tumor, Shionogi Carcinoma 115. The nucleotide sequence of the receptor revealed two different forms, designated as SC-GR I and SC-GR II. Both forms have a one-base substitution in the DNA binding domain of the wild-type mouse glucocorticoid receptor. Furthermore, SC-GR II has a three-base insertion in the interfinger region of this domain. By expressing the receptor cDNAs in cultured cells with MMTV-CAT reporter plasmid, SC-GR II was found to have about half of the activity of the wild-type mouse glucocorticoid receptor induced by either physiological or pharmacological doses of dexamethasone. PMID- 2253791 TI - The histopathology of non-palpable breast lesions detected by clinical mammography. AB - An histological study of 227 non-palpable breast lesions detected by clinical mammography revealed 64 invasive carcinomas at a mean patient age of 60.5 years. There were 10 carcinomas in situ, mean age 57.2 years. Fibrocystic disease with intraductal epithelial hyperplasia was found in 41 specimens, mean age 54.3 years. Fibrocystic disease without intraductal hyperplasia was found in 57 biopsies, mean age 50.7 years. Histological microcalcifications were found in 113 biopsies, and were considered to be a marker for epithelial proliferation of both benign and malignant kinds. Microcalcifications detectable in histological sections and by mammography differ in size by a factor of 10 or more. This difference has to be considered when comparing histological and mammographic findings. PMID- 2253792 TI - The prognostic significance of marrow micrometastases in women with early breast cancer. AB - Twenty-five patients with early breast cancer (T0-T2, N0-N1, M0) have been studied prospectively to determine the relationship between marrow micrometastases, disease-free interval and survival. Marrow specimens were aspirated from three sites immediately prior to breast surgery. An immunocytochemical technique using monoclonal antibody LICR.LON.M8.4 was employed to detect micrometastases. The minimum follow-up was 38 months. Twelve of the 25 patients (48%) had micrometastatic lesions in their marrow at presentation. Four of these patients developed distal recurrence during follow-up, causing death in two of them. Five of the 13 patients with no evidence of micrometastases developed distant recurrence and four of them have died. There was no correlation between the state of the marrow and the development of metastatic disease, although axillary lymph node status, disease stage and tumour volume correlated significantly with outcome (all P less than 0.025). Micrometastatic lesions appear to be common in the marrow of patients with early breast cancer. We have been unable to demonstrate that they have prognostic significance. PMID- 2253793 TI - Comparison of conservative surgery and radiotherapy with mastectomy in the treatment of early breast cancer. AB - We have compared overall survival, and local and distant recurrence-free survival in patients with early breast cancer treated by mastectomy, with patients treated by wide local excision and radiotherapy. To do this, we reviewed a consecutive, unselected series of patients presenting with early breast cancer (T0-T2, N0-N1b, UICC) between 1973 and 1981 to one surgeon (J.-C.G.) and one radiotherapist (H.T.F.). The mean follow-up was 9 years (minimum 6 years, maximum 14 years). Only 9 patients received any adjuvant therapy. At 10 years the relapse-free survival was 65% for both groups of patients; the overall 10-year survival was 70% for patients treated by wide local excision and radiotherapy, and 67% for patients treated by mastectomy. The actuarial loco-regional recurrence rate at 10 years was 15% for patients treated by wide local excision and 13% for patients treated by mastectomy. There were no significant differences in overall survival, loco-regional and distant relapse-free survival between the two groups of patients. Our results support other reports that conservative surgery and radiotherapy in early breast cancer does not adversely affect long-term prognosis. PMID- 2253794 TI - Gastrointestinal tumours after stapler vs vicryl anastomoses in carcinogen treated rats. AB - Since nickel is a potent carcinogen the influence of nickel-containing staples on the frequency of gastrointestinal tumour formation was tested in caecum-resected and carcinogen-treated rats. Tumour formation was elevated after stapling compared with simple laparotomy or vicryl sutures. This demonstrates a potential hazard of stapling techniques. In the vicryl group there was only one suture line carcinoma. PMID- 2253795 TI - Evaluation of blood flow in human rectal tumours using a laser Doppler flowmeter. AB - A TSI laser Doppler flowmeter was used via a rigid sigmoidoscope in 20 consecutive patients with rectal carcinoma. Blood flow and velocity was evaluated at the tumour centre, tumour edge and adjacent normal mucosa; blood flow in the centre of the tumour was significantly higher than in normal mucosa (P = 0.05) and the tumour edge (P = 0.037). Two patients with ulcerated lesions had much lower blood flow in the centre of the ulcerative lesion. PMID- 2253796 TI - Adrenocortical carcinoma. A retrospective study of a rare tumor with a poor prognosis. AB - A retrospective study was performed on 54 patients diagnosed as having adrenocortical carcinoma during 1974-1983. The initial symptoms were often diffuse: abdominal pain, weight loss, or fever, and more than 60% of the patients showed no evidence of overproduction of hormone. The median tumor diameter was 13 cm and almost half of the tumors had metastasized at diagnosis. A radical tumor resection could be performed in less than 50% of the patients, and at histopathological re-examination some tumors were not conclusively verified as malignant. Capsular invasion, nuclear pleomorphism and mitoses were found more commonly in patients who succumbed to the disease. Seven of 29 patients treated with chemotherapy showed an objective response and two of them are still alive and free of disease. The overall 5-year-survival rate was 19%, compared with 45% for patients with radically resected tumors. Patients with no biochemical signs of overproduction of adrenocortical hormone appeared to have a better prognosis than those with hormone excess. Together with increased use of ultrasound and computed tomography, a urinary steroid profile might hopefully contribute to earlier discovery of these often clinically silent tumors. However, it remains to be determined whether these diagnostic improvements, together with more aggressive surgery and adrenolytic chemotherapy, can improve the poor prognosis. PMID- 2253797 TI - A malignant Leydig cell tumour associated with testicular trauma and prostatic carcinoma. AB - A case of metastatic Leydig cell carcinoma without sex hormone overproduction is reported. The patient had had a prior testicular contusion trauma on the same side after which the testicle had been swollen and firm. The possible aetiological role of extreme trauma is discussed. Radical orchidectomy is recommended for large tumours because of the difficulty in predicting malignant potential, and routine follow-up with retroperitoneal ultrasound scanning for 10 years in all cases. PMID- 2253798 TI - Radiation-induced sarcomas of the clavicle following treatment of Hodgkin's disease. Report of two cases. AB - Two patients who received combined chemo- and radiotherapy for Hodgkin's disease developed secondary tumors in irradiated fields by 15 and 24 years, respectively. All the necessary criteria for the diagnosis of radiation-induced sarcoma have been found. PMID- 2253799 TI - Postirradiation malignant transformation in benign haemangioma. AB - A malignant angiosarcoma developed at the site of a benign cavernous haemangioma 33 years after the lesion was treated with radiotherapy. The possible mechanisms for this association are discussed. PMID- 2253800 TI - Management of extremity soft tissue sarcoma. Miles Lecture. 1988. PMID- 2253801 TI - Quality assurance and the assurance of quality in the management of cancers detected in breast cancer screening: the role of BASO. PMID- 2253802 TI - A follow-up study of the ingestion of gellan gum by humans, with special reference to the absence of eosinophilia. AB - Following a 7-day control period, during which sampling was carried out on two occasions (days 1 and 8), 10 female and 10 male healthy volunteers consumed a weight of gellan gum corresponding to 175 mg/kg body weight for 7 days (days 8 14) followed by 200 mg gellan gum per kg body weight for a further 14 days (days 15-28). The total period of ingestion (21 days) was followed by a further 7-day control period (days 29-36). 'Control' samples for haematology and plasma clinical chemistry were therefore secured on days 1, 8 and 36, and 'test' samples were secured on days 15, 22 and 29. In addition, 24 h samples were monitored by urinalysis, and 24 h faecal samples were monitored for occult blood three times each week. The major objectives were to supplement the data for gellan gum obtained previously, particularly in respect of changes in eosinophil concentrations, and to re-examine the responses of two male volunteers who had given indications of eosinophilia in a previous study. There was no such response by them, or by any of the other 18 volunteers, on this occasion. PMID- 2253803 TI - Migration of plasticizer from poly(vinyl chloride) milk tubing. AB - Milk samples were collected from a dairy in Norway at various stages of the milking process in order to assess the extent of migration of di(2-ethyl hexyl)phthalate (DEHP) from plasticized tubing used in commercial milking equipment. In control milk samples obtained by hand milking, DEHP contamination was below 5 micrograms/kg, whilst for machine milking, concentrations in the milking chamber for each individual cow averaged 30 micrograms/kg and rose to 50 micrograms/kg in the central collecting tank. Retail pasteurized skimmed milk samples from Norway were found to contain 20 micrograms/kg DEHP, and two retail cream samples contained 1200 and 1400 micrograms/kg of DEHP, reflecting the association of plasticizer with the fat phase. Retail whole milks from the UK contained 35 micrograms/kg of DEHP. This contamination is believed to originate from environmental sources as DEHP plasticizer was not used in the milking equipment. PMID- 2253804 TI - Effect of dietary fats on endogenous formation of N-nitrosamines from nitrate in germ-free and conventional rats and rats harbouring a human flora. AB - Urinary excretion of N-nitrosoproline (NPRO) was measured in groups of four germ free (GF) and conventional (CV) rats given a purified diet with or without inclusion of 100 g butterfat, coconut oil or maize oil/kg, and drinking water containing 0.235 M-NaNO3. In the CV environment rats given the fat-supplemented diets excreted significantly less NPRO than those on the low-fat diet. No corresponding decrease in NPRO excretion occurred in the GF environment. Nitrate reductase activity was measured in stomach contents and homogenates of stomach tissue from GF and CV rats given the different diets. No activity was detected in any of the contents from GF rats. Nitrate reductase activity was significantly reduced in contents from all the CV rats given the fat-supplemented diets, the effect being most marked in those given butterfat. Activity was much lower in tissue homogenates from GF rats than in those from their CV counterparts, but was not affected by diet in either environment. Groups of four CV rats, or rats harbouring a human faecal flora (HF), were given the purified diet with or without addition of 100 g butterfat or maize oil/kg and drinking water containing 0.235 M-NaNO3. All groups given the fat-supplemented diet with the exception of the HF rats given butterfat. It is concluded that the reduced excretion of NPRO by rats given diets containing fat was mainly due to inhibition of microbial nitrate reductase activity in the foregut. The smaller effect of butterfat on the HF rats accords with earlier findings in human subjects. PMID- 2253805 TI - An investigation of the levels of N-nitrosodimethylamine, apparent total N nitroso compounds and nitrate in beer. AB - Over 170 retail samples of beer have been analysed for N-nitrosodimethylamine (NDMA), apparent total N-nitroso compounds (ATNC) and nitrate. Levels of NDMA ranged from below 0.1 up to 1.2 micrograms/kg with a mean of 0.2 micrograms/kg. ATNC was detected in 42% of the samples in concentrations of up to 569 micrograms (N-NO)/kg. The levels of nitrate ranged from less than 0.2 up to 143 mg/kg with a mean of 16.8 mg/kg. There was no correlation between the amounts of NDMA and ATNC found in the retail beers. Samples taken during the course of fermentation showed that NDMA was unaffected by the bacterial reduction of nitrate which causes ATNC formation. HPLC studies using a photolysis/chemiluminescence detector revealed that the ATNC in beer are highly polar species of as yet unknown identity. PMID- 2253806 TI - Mycotoxin production in amber durum wheat stored at 15 and 19% moisture content. AB - Ochratoxin A and citrinin developed in 11 kg parcels of amber durum wheat at 15% and 19% initial moisture content (MC) exposed to simulated bulk storage in a Manitoba granary for 60 weeks between July 1984 and September 1985. Other biotic and abiotic variables were monitored throughout the storage period. Ochratoxin A reached maximum levels of 11.8 and 0.11 ppm at 19 and 15% initial MC, respectively, during weeks 44-48; citrinin reached levels of 80.0 and 0.65 ppm at these respective moistures during the same period. The effect of 19% initial MC was significantly greater for the following variables: ochratoxin A, citrinin, Aspergillus flavus, Aspergillus glaucus group species, Alternaria species, Aspergillus versicolor, bacteria, fungal propagule count, seed germination, O2, CO2, moisture content, and fat acidity. Principal component analysis indicated that the first two components, describing greater than 60% of the variability in the data, partially defined the ecological relationships leading to mycotoxin production in the stored durum wheat system. PMID- 2253807 TI - Organochlorine and organophosphorus residues in the fat of domestic farm animal species, Ontario, Canada 1986-1988. AB - During the period 1986-1988 a total of 602 samples of animal products were analysed for organochlorine and organophosphorus pesticides and industrial organic pollutants. Samples of abdominal fat were collected from avian, bovine, caprine, lupine, ovine and porcine species together with hen eggs. The following six compounds were identified in animal tissues: DDE, dieldrin, lindane, PCB, pentachlorophenol and tetrachlorophenol. Pentachlorophenol was the most frequently found contaminant, being identified in 35% of samples, and DDE was the second in 21%. All other contaminants were present in less than 10% of samples. The residues of all six compounds detected were added to give a combined residue. Forty-three per cent of samples had non-detectable residues. A further 31% had combined residues adding to less than 0.01 mg/kg. The highest combined residues ranged between 0.1 and 1.0 mg/kg and were present in 2.8% of samples. One egg sample had a residue of 0.16 mg/kg that exceeded the 0.1 mg/kg maximum residue limit for pentachlorophenol. Residues of chlordane and its metabolites, heptachlor and its epoxide, endosulphan and its sulphate metabolite, dicofol, HCB and mirex were below their detection limits in all samples and no residues of the organophosphorus insecticide listed as applied to livestock were found in meat, fat or egg tissues. PMID- 2253808 TI - Residues of insecticides, and fungicides in fruit produced in Ontario, Canada, 1986-1988. AB - Between 1986 and 1988, 306 composite samples of fruit representing eight commodities were collected from farm deliveries to the marketplace in Ontario, Canada. All samples were analysed for insecticides and fungicides. The analysis procedure included tests for organochlorine, organophosphorus, synthetic pyrethroid and methylcarbamate insecticides and dithiocarbamate, dicarboximide and organochlorine fungicides. The commodities tested included apples, blueberries, cherries, grapes, peaches, pears, raspberries and strawberries. In 14% of all fruit samples, pesticide residues were below the detection limits, which ranged between 0.005 and 0.02 mg/kg. A further 14% had total combined pesticide residues below 0.1 mg/kg. Total combined fungicide and insecticide residues ranged from 0.1 to 11 mg/kg in 72% of samples. Six different pesticides were in violation of maximum residue limits (MRL) on 11 (3.6%) of fruit samples. Captan exceeded the 5 mg/kg MRL in five samples and EBDC exceeded the 7 mg/kg MRL in two. Other violations included single fruit samples with dicofol, endosulphan, phosalone and iprodione above the MRL. Raw grapes harvested for wine contained residues of 10 pesticides and the number changed little following the crushing of the grapes; however, fermentation into wine significantly reduced residues. Six insecticides and four fungicides were present on the raw grapes and 4/105 were above the MRL. Following crushing, four insecticides and five fungicides were identified and 4/40 were above the MRL. In wine only three insecticides were identified and all were well below the MRL. Carbaryl appeared to be the most persistent, declining very little between raw grapes and wine. PMID- 2253809 TI - A survey of the occurrence of agaritine in U.K. cultivated mushrooms and processed mushroom products. AB - The naturally occurring compound agaritine (beta-N-[gamma-L(+)glutamyl]-4-hydroxy methylphenyl-hydrazine) has been determined in fresh, dried and processed mushrooms. A method was developed involving extraction of the toxin into methanol, clean-up where appropriate (for processed products) by high-performance size exclusion liquid chromatography and determination by reverse-phase HPLC with electrochemical detection. Diode array UV monitoring was used for confirmation. The method had a recovery of 90-98%, a relative standard deviation of 3-5% and a limit of detection of agaritine of 5 mg/kg on a dry-weight basis. Fresh cultivated mushrooms showed agaritine levels of 100-250 mg/kg and 80-190 mg/kg for two different commercial strains. There were slight differences in levels of agaritine between mushrooms of different sizes, and between those of the same size but harvested at different times (different breaks). Retail processed mushrooms products had low agaritine levels in the range 6-33 mg/kg, with the exception of one dried sliced mushroom product found to contain 6520 mg/kg. PMID- 2253810 TI - Fungal metabolites of sorbic acid. AB - A number of fungal detoxification reactions of sorbic acid have been reviewed. These include decarboxylation to give trans-1,3-pentadiene, esterification to give ethyl sorbate, reduction to give 4-hexenol and 4-hexenoic acid. It was shown that seven Penicillium species could convert sorbic acid into 1,3-pentadiene whilst P. bilaii, P. fellutanum and P. glabrum did not. However, most Eurotium species were unable to bring about this conversion. Considerable differences in the resistance of two isolates of P. crustosum to sorbic acid were found. An isolate from coconut was more resistant than one isolated from hazelnuts. Both sorbic acid and caproic acid (hexanoic) brought about disorganization of the mitochondrial membranes in P. crustosum. It is suggested that these lipophilic acids inhibit growth by interfering with the electrochemical membrane potential across the mitochondrial membranes. PMID- 2253811 TI - Toxicology of sorbic acid and sorbates. AB - Sorbic acid and its salts have been subjected to an extensive battery of tests, including acute, short-term and chronic toxicity/carcinogenicity tests, two generation reproduction and teratogenicity studies. These studies show that sorbic acid and sorbates have a very low level of mammalian toxicity, even in chronic studies at up to 10% of the diet, and are devoid of carcinogenic activity. They are non-mutagenic and non-clastogenic in vitro and in vivo. The low toxicity is explicable by the fact that sorbic acid is metabolized rapidly by similar pathways to other fatty acids. In humans, a few cases of idiosyncratic intolerances have been reported (non-immunological contact urticaria and pseudo allergy). The frequency appears low but there are too few reported data for an accurate assessment of the true incidence. In extreme conditions (high concentrations and temperature) sorbic acid may react with nitrite to form mutagenic products but these mutagens are not detectable under normal conditions of use, even in curing brines. PMID- 2253812 TI - Stability of sorbic acid in intermediate moisture systems. AB - Intermediate foods are a heterogeneous group of foods which are stabilized by lowering their water activity to a level insufficient to support bacterial growth, typically about 0.85. However, moulds and yeasts are able to grow at these water activities and it is usual to add an antimycotic such as sorbate to ensure microbial stability. Sorbate, though, is liable to oxidation and in model systems adjusted to a water activity of 0.85 some of the oxidation products were found to be potential reactants in non-enzymic browning reactions with lysine, glutamate and haemoglobin solutions when stored at 38 degrees C or 65 degrees C. Oxidation led to an increase in pH and the formation of thiobarbituric acid reactive substances. In some intermediate moisture meat products prepared by cook soak equilibration in a variety of humectant solutions, 0.3% sorbate induced the formation of covalent linkages between proteins on storage at 38 degrees C. The concentration of sorbate in the meats decreased by a factor of 2 during 4 months at this temperature. The effects of such reactions on the quality of the food are discussed. PMID- 2253813 TI - Nucleophilic reactions of sorbic acid. AB - The conjugated dienoic acid structure of sorbic acid renders it susceptible to nucleophilic attack. Nucleophiles known to react with sorbic acid include sulphite ion and amines. These attack the molecule in position 5 and, in the cse of amines, cyclization to form substituted dihydropyridones may follow. Recent investigations show that thiols in general can also add to sorbic acid. Cysteine, for example, reacts slowly with sorbic acid at 80 degrees C and pH 5.5, leading to 5-substituted 3-hexenoic acid. In general, reaction products are difficult to isolate from aqueous reaction mixtures as they are susceptible to acid- and base catalysed hydrolysis. A synthesis of model compounds may be carried out by reaction of sorbate esters with the appropriate thiol (or its ester if it is an acid) in the presence of the corresponding sodium alkoxide. It is interesting that alkyl thiols give di-adducts with sorbate ester whilst low molecular weight thiols containing an oxygen atom give a monoadduct. The mechanism of this reaction and its implications to the preparation of samples for toxicological evaluation are discussed. The reaction of sorbic acid with nitrite ion is unusual and its mechanism is considered. PMID- 2253814 TI - Effect of surfactants and dispersed components on the activity and reactivity of sorbic acid. AB - In common with many other carboxylic acids, sorbic acid shows significant solubility in aqueous and non-aqueous solvents. The presence of a non-aqueous phase (e.g. fat) can markedly affect the concentration of the preservative in the aqueous phase. Solute distribution between the two phases is pH- and concentration-dependent. The presence of dissolved surfactants in the aqueous phase will also affect the activity of sorbic acid. This effect is due to the partitioning of the solute into surfactant micelles. The presence of dispersed components and surfactant micelles also has a marked effect on the reactivity of sorbic acid. Whereas thiols react slowly with sorbic acid, the rate of reaction is increased many-fold by the addition of low molecular weight surfactants. The mechanism of this catalysis will be explained. It has been suggested that sorbic acid inhibits enzymes by reacting with sulphydryl groups of the proteins. Kinetic data from model system studies suggest that the sorbic acid-thiol reaction may be too slow for it to be an obvious means of enzyme inhibition. However, this does not take account of possible catalysis of the reaction in the microenvironment of the protein, perhaps in a manner similar to that identified with low molecular weight surfactants. PMID- 2253815 TI - Food applications of sorbic acid and its salts. AB - Because of their physiological inertness, their effectiveness even in the weakly acid pH range and their neutral taste, sorbic acid and its salts have become the leading preservatives in the food sector throughout the world over the past 30 years. The most commonly used products are sorbic acid itself (E200) and potassium sorbate (E202). In many countries sodium sorbate (E201) and calcium sorbate (E203) are also permitted. Sorbic acid is sparingly soluble in water, sodium sorbate has better solubility, and potassium sorbate is very freely soluble and can be used to produce 50% stock solutions. The soluble sorbates are preferred when it is desired to use the preservative in liquid form, or when aqueous systems are to be preserved. Sodium sorbate in solid form is unstable and very rapidly undergoes oxidation on exposure to atmospheric oxygen. It is therefore not produced on the industrial scale. Aqueous solutions of sodium sorbate remain stable for some time. Calcium sorbate is used in the manufacture of fungistatic wrappers because it is highly stable to oxidation, but this use is very limited. Sorbic acid and sorbates can be directly added into the product. The products can be dipped or sprayed with aqueous solutions of sorbates. Dusting of food with dry sorbic acid is also possible but less recommended because sorbic acid irritates the skin and mucous membranes. Sorbic acid and particularly calcium sorbate can be used as active substances in fungistatic wrappers. A general survey of the numerous uses of sorbic acid in the food sector will be given. Some fields of application will be discussed that are either unimportant or not permitted in the U.K. PMID- 2253816 TI - Infant's response to social separation reflects adult differences in affiliative behavior: a comparative developmental study in prairie and montane voles. AB - As part of a comparative study of affiliative behavior, pups of two different vole species, Microtus ochrogaster (prairie voles) and M. montanus (montane voles), were compared for their responses to social isolation during the first 2 weeks of postnatal life. Previous studies have demonstrated that under both laboratory and field conditions, adult prairie voles show higher levels of affiliation than adult montane voles, although the species closely resemble each other morphologically. In the current study, prairie vole and montane vole pups showed profound differences in the behavioral and physiologic responses to social isolation. During 5 minutes of isolation, prairie vole pups emitted 314 +/- 60 (days 4-6) and 601 +/- 55 (days 8-10) ultrasonic vocalizations. At these same ages, plasma corticosterone increased 4-6 fold within 30 minutes of separation. The increase in corticosterone was highly correlated with the number of calls (r = .66). In contrast, most montane vole pups emitted no isolation calls under identical conditions. Moreover, montane vole pups had equivalent baseline corticosterone concentrations, but showed only a minor increase in corticosterone following separation at 4-6 days with no increase apparent at 8-10 days. As montane vole pups were capable of producing high levels of ultrasonic vocalizations and increased concentrations of plasma corticosterone in response to known stressors (tail suspension and halothane vapors), these results suggest that social isolation evokes less distress for montane vole pups than for prairie vole pups. The developmental difference in the amount of parent-young contact was not a sufficient explanation for the differences in the response to separation as cross-fostered montane voles failed to show an increase in ultrasonic vocalizations (although a slight increase in corticosterone was observed). Taken together, these studies indicate that species-typical adult patterns of affiliation may be apparent early in development in the response of infants to social separation. PMID- 2253817 TI - Endocrine responses to mother-infant separation in developing rats. AB - Separation of neonatal rat pups from the dam have been reported to elicit two endocrine responses in the pup: a fall in growth hormone secretion and a rise in corticosterone secretion. However, the temporal, ontogenetic, and behavioral determinants of these responses have not been compared. In the present study, we report that these two responses can be differentiated on each of these criteria. Growth hormone secretion falls rapidly immediately upon separation of pups from the dam, while robust rises in corticosterone secretion are delayed for many hours. In addition, growth hormone responses are observed earlier in ontogeny. Finally, active maternal behavior is required for normal growth hormone secretion in 10-day-old rat pups, while passive sensory stimuli associated with the dam can significantly reduce the corticosterone response to separation. PMID- 2253818 TI - Inhibition of infant glucocorticoid stress response: specific role of maternal cues. AB - Previous work from this laboratory has shown that passive contact with an anesthetized lactating dam eliminates the corticosteroid stress response to novelty in 12-, 16-, and 20-day-old rat pups. In the present study, we further examined some of the sensory and developmental aspects of this phenomenon. In two experiments, we asked whether inhibition of the corticosteroid stress response is related exclusively to contact with a maternal stimulus as opposed to other social stimuli. Experiment I compared the effectiveness of contact with an anesthetized dam vs, an anesthetized adult male rat. At 12 and 16 days of age, contact with an adult male was somewhat effective in reducing stress responsiveness, whereas at 20 days, contact with an adult male was entirely ineffective. At all ages, contact with an anesthetized dam was an effective inhibitor of the stress response. Experiment II compared the relative effectiveness of contact with an anesthetized dam vs. an anesthetized sibling pup. At all ages, contact with a dam was very effective, whereas contact with an anesthetized pup was entirely ineffective in inhibiting the glucocorticoid stress response. In Experiment III, the effect of maternal contact was assessed during a period of development when the biological, and presumably social, significance of the lactating-dam stimulus is changing. In this study, 20-, 24-, and 28-day-old rat pups revealed a progressive decrement in the ability of maternal contact to inhibit stress responsiveness. These findings replicate and extend our previous ones by showing that maternal stimuli play a special role in the modulation of pituitary-adrenal activity during development. PMID- 2253819 TI - The effect of early experience on water maze spatial learning and memory in rats. AB - In the first of two experiments on spatial competence, groups of light-reared (LR) and dark-reared (DR) rats were compared using a "latent learning" variation of the Morris Water Maze task. On their initial test, the LR rats benefited more than DR rats did from viewing the room/pool from a platform in the correct location. Further, visually experienced rats remember the location of the platform more than DR rats when retested one month later. In a second experiment, in which a proximal cue as well as location was varied from trial to trial. LR rats again proved to be more competent than their DR counterparts. This second task also revealed significant benefits related to stimulation history in the case of a third group of animals raised in enriched or complex environment (CR) conditions. The results are discussed in terms of the nature of the impact of early experience on the ability to acquire and remember spatial concepts. PMID- 2253820 TI - Striking absence of long-lasting effects of early color deprivation on monkey vision. AB - A monkey (Macaca fascicularis) spent its first three months under far red illumination that made color vision impossible. It developed normal spectral sensitivity. In the present study we examined two aspects of color vision that presumably reflect cortical connectivity. In the first part of this article we show that chromatic induction was also unaffected: a blue surrounding made a gray target appear to be yellow to the monkey. At five months of age, the deprived monkey did not readily use color to recognize objects, although it was able to do so if necessary. In the second part of this article we show that, as an adult, the monkey was quite willing to use color to categorize objects. We conclude that early color deprivation does not result in long lasting deficits in color vision. PMID- 2253821 TI - Predictive factors for the response of ulcerative colitis patients during the acute-phase treatment. AB - Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2 microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase. PMID- 2253822 TI - Effect of parietal cell vagotomy and cholinergic blockade on gastrin release in man induced by gastrin-releasing peptide. AB - The influence of cholinergic blockade as well as vagal denervation of the oxyntic gland mucosa on the gastrin response to gastrin-releasing peptide (GRP) have been studied in patients with duodenal ulcer disease. The gastric luminal content was neutralized during the experiments. GRP induced a substantial increase in gastrin levels with a peak response already after 15 min of infusion. Vagal denervation of the parietal cell area induced a significant increase in basal gastrin concentrations and a significant enhancement of the GRP response. Two different doses of benzilonium bromide were studied and neither influenced the basal concentrations of gastrin. A significantly increased gastrin response to GRP was, however, observed after administration of both a high and a very low dose of the anticholinergic drug. Our results delineate a vagal, noncholinergic inhibitory influence on the basal gastrin release. In addition a vagally dependent oxyntopyloric mechanism inhibits the gastrin release stimulated by GRP. This inhibitory mechanism may hypothetically be a cholinergic reflex mechanism. PMID- 2253823 TI - Effect of cimetidine on hepatic vitamin D metabolism in humans. AB - Cimetidine inhibits the action of vitamin D-hydroxylase (a hepatic mixed-function oxidase) in the rat. Therefore, the hypothesis was tested that this H2 receptor antagonist would affect vitamin D metabolism in humans. Nine adult patients were treated with 400 mg cimetidine orally twice daily during a period from winter to summer, when days were becoming longer. Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were monitored before treatment, after 4 weeks of treatment, and 1 month after cessation of treatment. No seasonal increase in the level of 25-hydroxyvitamin D was observed during the period of treatment, but the level rose significantly after withdrawal of the drug. The other hydroxylates of vitamin D were not affected. Levels of albumin, total calcium, phosphorus and alkaline phosphatase remained normal. The data suggest that short-term treatment with cimetidine could potentially perturb vitamin D metabolism in man. PMID- 2253824 TI - Medical treatment of antral gastrin cell hyperfunction: role of nonantisecretory therapy. AB - Antral G cell hyperfunction (AGCH) is a rare condition, often associated with severe duodenal ulcer disease poorly responsive to medical therapy. Up to now, no studies have been designed to investigate a possible role of medical treatment in the management of this syndrome. In this study we treated 9 AGCH patients with duodenal ulcer, unhealed with the prolonging standard doses of H2 antagonists (300 mg/day ranitidine or 800 mg/day cimetidine), with a nonantacid therapy, tripotassium dicitrato bismuthate (TDB). 6 out of 9 patients showed a complete healing after 8 weeks of treatment. The healing was irrespective to eradication of Campylobacter pylori. After 9 weeks' suspension of H2 blockers basal gastrin levels decreased significantly by 31.5%, whereas peak meal-stimulated levels, although decreased in 6 out 9 patients, were not significantly affected by the withdrawal of the H2 antagonists. Nonantisecretory therapy seems to be an efficacious alternative in the management of AGCH patients. PMID- 2253825 TI - Lung cavities in patients with coeliac disease. AB - The clinical, radiological and pathological features of 7 patients with coeliac disease (CD) who developed lung abscesses or cavities are described. These patients were seen during a 20-year period during which time approximately 600 coeliacs were seen and 50 died. Six of the coeliac patients with lung abscess died. The patients were middle aged. Staphylococcal infection, Klebsiella pneumoniae, bronchial carcinoma and previous pulmonary tuberculosis accounted for the cavities in 4 patients. In the 3 other patients a definite cause could not be identified. Hyposplenism and malnutrition were common. Next to malignancy pulmonary abscess was the commonest cause of death in the coeliac population. The development of respiratory symptoms should be regarded as a potentially serious and a life-threatening event in the middle-aged coeliac patients. Lung abscess should be added to the list of respiratory diseases associated with coeliac disease. PMID- 2253826 TI - Magnesium and glucose homeostasis. AB - Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been recently studied. In particular it has been shown that magnesium plays the role of a second messenger for insulin action; on the other hand, insulin itself has been demonstrated to be an important regulatory factor of intracellular magnesium accumulation. Conditions associated with insulin resistance, such as hypertension or aging, are also associated with low intracellular magnesium contents. In diabetes mellitus, it is suggested that low intracellular magnesium levels result from both increased urinary losses and insulin resistance. The extent to which such a low intracellular magnesium content contributes to the development of macro- and microangiopathy remains to be established. A reduced intracellular magnesium content might contribute to the impaired insulin response and action which occurs in Type 2 (non-insulin-dependent) diabetes mellitus. Chronic magnesium supplementation can contribute to an improvement in both islet Beta-cell response and insulin action in non-insulin-dependent diabetic subjects. PMID- 2253827 TI - Arrest of glomerulopathy in diabetic dogs by improved glycaemic control. AB - In order to assess the extent to which the progression of diabetic glomerulopathy can be arrested or reversed by improved glycaemic control, glomerular structure has been assessed in dogs randomly divided between a non-diabetic group and three alloxan diabetic groups: dogs assigned to poor glycaemic control for five years (PC), dogs assigned to good glycaemic control for five years (GC), and dogs assigned to poor glycaemic control for 2.5 years followed by good glycaemic control for 2.5 years (P----GC). Glomerular volume, the fractional volume of mesangium as estimated by light microscopy and thickness of glomerular basement membrane as estimated by electron microscopy were significantly greater than normal at 2.5 years of poor glycaemic control, and were even greater at five years. Kidney weight and the frequency of glomerular obliteration were significantly greater than normal at five years of poor control. The development of these renal abnormalities was significantly inhibited if good glycaemic control was begun within the first weeks of diabetes. Good control following 2.5 years of poor control (group P----GC) arrested the progression of the renal abnormalities, but no reversal of the lesions toward normal was apparent. PMID- 2253828 TI - Impaired glucose tolerance in a middle-aged male urban population: a new approach for identifying high-risk cases. AB - From an urban population (n = 9,033) of 47-49-year-old males, 6,956 participated in a multiphase screening programme, of whom 1.5% were already registered as diabetic patients, 1.7% were then found to be diabetic; of 6,325 subjects given oral glucose tolerance tests, 6.6% were found to have impaired glucose tolerance (WHO criteria, 1985). In 889 asymptomatic cases with initial capillary whole blood glucose values greater than or equal to 6.6 mmol/l fasting and/or 2 h post load, fluctuation in oral glucose tolerance was studied at repeat tests within one month; the mean differences in glucose values between the first and second test were less than -1% (fasting) and -15% (2 h post-load); there were no differences in body weight, and 62% of those with initially impaired glucose tolerance had normalised by the repeat test. Only in 109 cases (1.7%) were 2 h post-load values in the 7.8-11.0 mmol/l range both at the first and the repeat test; these cases were comparable vis-a-vis body mass index, triceps skin fold, blood pressure and initial glucose and insulin values, but had significantly lower oxygen uptake (2.34 +/- 0.54 l/min vs 2.63 +/- 0.68 l/min; p less than 0.003), as compared with subjects with initially impaired glucose tolerance but normal repeat test outcome. However, subjects with high normal first test results (2 h value in the 7.0-7.7 mmol/l range) and second test results in the 7.0-11.0 mmol/l range, resembled those with persistent impairment of glucose tolerance in all respects (including oxygen uptake). The repeat test procedure (including ergometry), is therefore to be recommended in selecting true risk cases. PMID- 2253829 TI - The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects. AB - Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253830 TI - A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) I: Causes and death rates. AB - The 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics have been followed for mortality from 1975 to 1987. During this period 92 patients died. The most common cause of death was myocardial infarction: 36 (39.1%) deaths, heart disease was responsible for 51.1% of deaths and all cardiovascular disease for 55.4%. Neoplastic disease accounted for 25% of the deaths and diabetic nephropathy for 5.4%. Age-standardised mortality rates were higher in men than in women in both Type 1 (insulin-dependent) diabetes and Type 2 (non-insulin-dependent) diabetes. Standardised mortality ratios for the first and second five year follow-up periods were higher for men than for women in Type 2 diabetes but were higher for women than men in Type 1. The results suggest that the female survival advantage seen in the general population may persist in Type 2 but not in Type 1 diabetes. PMID- 2253831 TI - A prospective study of mortality among middle-aged diabetic patients (the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: Associated risk factors. AB - Potential risk factors have been examined for association with mortality over a 10-12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35-54 years at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 4.6 [corrected] in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253832 TI - Reduction of insulin resistance by combined kidney-pancreas transplantation in type 1 (insulin-dependent) diabetic patients. AB - To evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy. 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisone-treated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that short-term (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance. PMID- 2253833 TI - Elevated serum placental isoferritin in newly diagnosed type 1 (insulin dependent) diabetes mellitus. A possible marker for identification of high risk subjects. AB - Placental isoferritin is produced by activated T lymphocytes and may, therefore, be considered as a manifestation of T cell involvement. Placental isoferritin is measured using CM-H-9 monoclonal antibody which binds exclusively to placental isoferritin. Placental isoferritin has been determined in the serum of 80 patients with Type I (insulin-dependent) diabetes mellitus, 100 healthy first degree relatives and 81 healthy children. Serum levels which were measured in Type 1 diabetic patients, (24.0-140 U/ml; median and range) were significantly higher than those of family members (0,0-73; median and range; p less than 0.0001) and normal control subjects (0,0-48; median and range; p less than 0.0001). Using 0-10 U/ml as the upper limit of normal, it was found that 31 of 50 (62%) of Type 1 diabetic patients, 25 of 100 (25%) family members and 7 of 81 (8.6%) healthy control subjects had abnormal placental isoferritin levels. Islet cell antibodies were positive in 31 of 44 tested diabetic patients and, in 8 of 71 tested family members, and among them 54.8% and 50% respectively also had elevated placental isoferritin levels. However, no statistically significant correlation was found between islet cell antibodies and placental isoferritin levels. Treatment of Type 1 diabetic patients with insulin was accompanied by a significant decrease (p less than 0.002) of serum placental isoferritin within 2 4 weeks of treatment. It is noteworthy that placental isoferritin was below detection in 34 of 35 Type 2 (non-insulin-dependent) diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253835 TI - Tumour necrosis factor alpha production is upregulated in diabetes prone BB rats. AB - Following activation peritoneal macrophages from diabetes prone BB rats secreted strikingly higher amounts of tumour necrosis factor alpha than found for macrophages from diabetes resistant or normal Wistar rats. Enhanced tumour necrosis factor alpha production was detected prior to the occurrence of insulitis. Cultures of macrophages derived from precursor cells in diabetes prone BB rat bone marrow also showed upregulated tumour necrosis factor alpha secretion upon challenge with endotoxin and interferon gamma. Tumour necrosis factor alpha hypersecretion may contribute to autoimmune diabetes by affecting thymic and post thymic T-cell maturation and by promoting pancreatic islet inflammation. PMID- 2253834 TI - Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus. AB - The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmo (230,000 inhabitants), corresponding to an incidence rate of 53.100,000(-1).year-1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow up (n = 233) after a median time of 31 (range 1-49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p less than 0.001), higher HbA1c (p less than 0.004), and lower C-peptide (p less than 0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence. PMID- 2253836 TI - Blood rheology and diabetic nephropathy. PMID- 2253837 TI - The activity of 2,5-oligoadenylate synthetase, an interferon-induced enzyme, is coupled to the differentiation state of mouse condylar cartilage. AB - The enzyme 2,5-oligoadenylate synthetase (2-5A synthetase) is associated with the interferon system, with special reference to the differentiation process of various cell types. The present study investigated whether 2-5A synthetase is also involved in the differentiation of neocartilage in perinatal mice. The cartilage of the mandibular condyle, a secondary type of cartilage, develops relatively late in prenatal life; and consequently it was possible to obtain a relatively embryonic cartilage at a developmental stage that could be manipulated enzymatically, in order to separate and thereby obtain its undifferentiated, proliferative portion along with its more mature fraction. Immunohistochemical studies using antibodies against type I and type II collagen and cartilage specific proteoglycans could have determined the differentiation status of various portions of the developing condyle. However, the above methodology lacks the necessary precision and accuracy to indicate subtle changes in cellular differentiation. It became evident that the activity of 2-5A synthetase was indeed different in cellular compartments that were at different stages of differentiation. In the neonatal condyle the highest level of activity was encountered in proliferating and as yet undifferentiated prechondrocytes, whereas fully differentiated chondrocytes showed a marked decrease in the activity of this enzyme. PMID- 2253838 TI - Complexities and sequence similarities of mRNA populations of cholinergic (NS20 Y) and adrenergic (N1E-115) murine neuroblastoma cell lines. AB - The clonal murine neuroblastoma cell lines NS20-Y and N1E-115 have been proposed as models for examining the commitment of neural crest cells to either the cholinergic or adrenergic phenotype, respectively. The validity of this model depends in part on the extent to which these two cell lines have diverged as a result of their transformed, rather than neuronal properties. In order to quantitate differences in gene expression between NS20-Y and N1E-115 cells, the mRNA complexity of each cell type was determined. An analysis of the kinetics of hybridization of NS20-Y cell mRNA with cDNA prepared from NS20-Y cell mRNA demonstrated the presence of approximately 11,700 mRNA species assuming an average length of 1900 nucleotides. A similar analysis using mRNA isolated from N1E-115 cells and cDNA prepared from N1E-115 cell mRNA demonstrated that the adrenergic cell line expressed approximately 11,600 mRNA species. The species of mRNA expressed by each cell line were resolved into high, intermediate, and low abundance populations. In order to determine whether mRNAs were expressed by the cholinergic, but not by the adrenergic cell line, NS20-Y cDNA was hybridized to an excess of N1E-115 cell mRNA. An analysis of the solution hybridization kinetics from this procedure demonstrated that the two cell lines do not differ significantly in the nucleotide complexity of their mRNA populations. The extensive similarity between the two mRNA populations suggests that only a small number of genes are expressed differentially between the two cell lines and supports their use as models for the differentiation of cholinergic and adrenergic neurons. PMID- 2253839 TI - Expression of inhibin alpha-subunit gene during mouse gametogenesis. AB - Mammalian gametogenesis is regulated through complex interactions between germ and somatic cells. To investigate the mechanism underlying the differentiation of functional gametes, some genes specifically expressed during gametogenesis have been isolated and characterized. In a search for further examples of such genes, we have isolated from a newborn mouse testis cDNA library, a clone corresponding to mouse inhibin alpha-subunit. Although it is known that the inhibin alpha subunit molecule is abundantly produced in ovarian follicle and in testicular Sertoli cells, the spatial and temporal patterns of expression of this gene remain to be elucidated. In this study, the patterns of expression of inhibin alpha-subunit mRNA during mouse gametogenesis were examined by RNA blot, cytoplasmic dot and in situ hybridization techniques. In the testis, the concentration of inhibin alpha-subunit mRNA increased from about 16 dpc (days post coitum), peaked at birth and then gradually decreased, paralleling testicular development. Inhibin alpha-subunit mRNA was localized in Sertoli cells of wild type as well as W/Wv testes. In adult testis, mRNA was restricted to the perinuclear cytoplasm of Sertoli cells. Inhibin alpha-subunit mRNA was expressed in follicle cells of adult ovary more abundantly than in adult testis. Analysis of expression during folliculogenesis showed that the accumulation of this mRNA began in preantrum follicles and the level of expression reached a maximum in Graafian follicles. PMID- 2253840 TI - Activation of phenylalanine hydroxylase expression following genomic DNA transfection of hepatoma cells. AB - Genomic DNA from cells producing the liver-specific enzyme phenylalanine hydroxylase (PAH) should contain, in active form, genes encoding regulators of PAH expression. We have transfected genomic DNA from PAH-producing rat hepatoma cells to PAH-deficient mouse hepatoma cells, and selected in tyrosine-deficient medium for cells producing the enzyme. The frequency of colonies obtained was similar to that for transfer of a single-copy gene. Genomic DNA from the primary transfectants permitted the isolation in tyrosine-free medium of secondary transfectants. Control experiments, using donor DNA from PAH-negative rat or mouse hepatoma cells also permitted the isolation of PAH-expressing cells, but at a frequency 10-30 times lower. The transfectants isolated in tyrosine-deficient selective medium all produced PAH mRNA. This transcript was from the previously silent mouse gene, which had not undergone amplification or gross rearrangement. Most of the transfectants contained less than 0.1% rat DNA. A search for other functions that might have been simultaneously activated was negative. It is concluded that the mouse transfectants acquired from the PAH+ rat donor some sequences whose presence permits activity of the previously silent PAH gene. PMID- 2253842 TI - FASEB scientists' response to Institute of Medicine report on 'Funding Health Sciences Research'. PMID- 2253841 TI - Tissue-specific trans-activation of the rabbit beta-globin promoter in Xenopus oocytes. AB - Identification of transcription factors regulating tissue-specific gene expression implies functional tests in transcription systems. In spite of its practical advantages, the Xenopus oocyte has only rarely been used for trans activation studies, because some critical parameters inherent to the system may cause artefacts. Depending on the amount of DNA injected, even tissue-specific genes may be spontaneously transcribed. To develop a reliable trans-activation assay, we used the erythroid-specific rabbit beta-globin gene and, for comparison, the constitutively transcribed viral thymidine kinase gene. The viral gene is active over a wide range of injected DNA (0.2-10 ng), and addition of nuclear proteins from various cell types does not stimulate but often inhibits this activity. When large amounts of DNA are injected (greater than 10 ng), transcription is inhibited by self competition. Addition of nuclear proteins now re-establishes activity probably through increasing the pool of general transcription factors. By contrast, spontaneous activity of the beta-globin promoter occurs only within a narrow range of injected DNA (0.2-1 ng). At higher DNA concentrations (greater than 5 ng) spontaneous transcription becomes negligible. The addition of nuclear proteins from nonerythroid cells extracts has no or only a weak stimulatory effect on the beta-globin promoter. Only nuclear proteins isolated from erythroid tissues, bone marrow and spleen, bring about a strong transcriptional activation. Co-injection with either the polyoma virus, or the oviduct-specific chicken lysozyme gene shows that the beta-globin promoter is selectively activated by factors present in erythroid cell extracts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2253843 TI - The two binding-site models of human IgG binding Fc gamma receptors. AB - Fc receptors (FcR) are immunoglobulin-binding molecules that enable antibodies to perform several biological functions by forming a link between specific antigen recognition and effector cells. FcRs are involved in regulating antibody production as well. Most FcRs belong to the immunoglobulin superfamily, and show structural homology with each other and with their ligands. Recent data on the structure of IgG binding FcRs obtained from monoclonal antibodies and gene cloning studies, as well as on ligand binding capacity and fine specificity of the receptor binding site (or sites), are reviewed. The binding capacity and fine specificity of receptor binding sites, as well as the structure and conformation of the immunoglobulin ligands, play important roles in triggering FcR-mediated signals. In induction of signals, the interaction of the FcR with the CH2 domain of the IgGFc is decisive. The high-affinity Fc gamma RI possess one active binding site specific for contact residues that is located at the N-proximal end of the CH2 domain and is able to mediate both binding and signal transfer. The low-affinity Fc gamma RIII has two active binding sites: the CH3 domain-specific site, which mediates only binding; and the CH2 domain-specific site, which is responsible for binding and signaling. Similarly, the low-affinity Fc gamma RII on resting B cells has one site for CH2 and another for CH3 binding. The expression, release, and fine specificity of Fc gamma RII on B cells correlates with the cell cycle. PMID- 2253844 TI - Microtubule dynamics. AB - A combination of biochemical, structural, and morphological analyses during the last 2 decades has shown that the cytoplasm of a cell is not a disorganized mass of jelly but a highly structured cell compartment formed of a cytoskeleton, one of which principal components are the microtubules. More recently, studies have revealed that microtubule cytoskeleton is not only well organized but highly dynamic, and that microtubule dynamics may be responsible for several cell functions such as chromosome segregation, cell morphogenesis, or intracytoplasmic organization. PMID- 2253845 TI - Role of set-point theory in regulation of body weight. AB - In adult individuals body weight is maintained at a relatively stable level for long periods. The set-point theory suggests that body weight is regulated at a predetermined, or preferred, level by a feedback control mechanism. Information from the periphery is carried by an affector to a central controller located in the hypothalamus. The controller integrates and transduces the information into an effector signal that modulates food intake or energy expenditure to correct any deviations in body weight from set-point. Evidence for involvement of various factors and physiological systems in the control of food intake and regulation of body weight and fat are reviewed within the context of a control model. Current working hypotheses include roles for nutrients, dietary composition and organoleptic properties, hormones, neural pathways, various brain nuclei, and many neurotransmitters in the regulation of food intake. It is concluded that regulation of body weight in relation to one specific parameter related to energy balance is unrealistic. It seems appropriate to assume that the level at which body weight and body fat content are maintained represents the equilibria achieved by regulation of many parameters. PMID- 2253847 TI - Complete life cycle of the canid tapeworm, Echinococcus multilocularis, in laboratory rodents. AB - Mongolian gerbils, Meriones unguiculatus, when treated at intervals of 2-6 days with prednisolone tertiary butyl acetate, sustained infection with adult Echinococcus multilocularis in the small intestine, with the tapeworm exhibiting normal strobilation and egg production as in the natural canid host. Host age is critical for the survival of the tapeworm in normal gerbils; parasites survive for only 2 days in 20-wk-old animals, 4 days in 4-wk-old animals, but at least 7 days in 3-wk-old animals. The host age dependence in parasite recovery between days 28-37 postinfection was not affected by treatment from around the day of infection. Starting the treatment before infection (on day -17 relative to infection) remarkably improved the tapeworm's survival within the intestine of older animals. Eggs produced in this rodent model system 28 days postinfection were infective to rodents such as Mongolian gerbils and gray red-backed voles, Clethrionomys rufocanus bedfordiae, by oral or intraperitoneal inoculation. The E. multilocularis/Mongolian gerbil system can replace the natural canid hosts as a new way to obtain infective eggs and to analyze host-parasite interactions. The development of an alternative definitive host for zoonotic tapeworms may accelerate experimentation in this field. PMID- 2253846 TI - Biosynthesis and urinary excretion of methyl sulfonium derivatives of the sulfur mustard analog, 2-chloroethyl ethyl sulfide, and other thioethers. AB - Thioether methyltransferase was previously shown to catalyze the S adenosylmethionine-dependent methylation of dimethyl selenide, dimethyl telluride, and various thioethers to produce the corresponding methyl onium ions. In this paper we show that the following thioethers are also substrates for this enzyme in vitro: 2-hydroxyethyl ethyl sulfide, 2-chloroethyl ethyl sulfide, thiodiglycol, t-butyl sulfide, and isopropyl sulfide. To demonstrate thioether methylation in vivo, mice were injected with [methyl-3H]methionine plus different thioethers, and extracts of lungs, livers, kidneys, and urine were analyzed by high-performance liquid chromatography for the presence of [3H]methyl sulfonium ions. The following thioethers were tested, and all were found to be methylated in vivo: dimethyl sulfide, diethyl sulfide, methyl n-propyl sulfide, tetrahydrothiophene, 2-(methylthio)ethylamine, 2-hydroxyethyl ethyl sulfide, and 2-chloroethyl ethyl sulfide. This supports our hypothesis that the physiological role of thioether methyltransferase is to methylate seleno-, telluro-, and thioethers to more water-soluble onium ions suitable for urinary excretion. Conversion of the mustard gas analog, 2-chloroethyl ethyl sulfide, to the methyl sulfonium derivative represents a newly discovered mechanism for biochemical detoxification of sulfur mustards, as this conversion blocks formation of the reactive episulfonium ion that is the ultimate alkylating agent for this class of compounds. PMID- 2253848 TI - DNA modification in vivo by derivatives of glucose: enhancement by glutathione depletion. AB - When BHK or HTC cells are cultured for 20 min with [U-14C]glucose in the presence of agents that deplete reduced glutathione, DNA banded from the cells in cesium salt gradients containing guanidium HCl is radioactively labeled. This depletion dependent labeling required live cells. It was not caused by reactive contaminants in the radioactive glucose preparations, by carbohydrate or protein comigration into the DNA band, or by metabolism of glucose into deoxyribose. Labeling levels are similar whether depletion is achieved by oxidation (with the drug diamide) or by inhibition of synthesis (with methionine sulfoximine). A temporal association between GSH repletion and the appearance of D-lactate, the putative unique product of GSH-dependent glyoxylase action on pyruvaldehyde, suggests possible involvement of 3-carbon dicarbonyls. PMID- 2253849 TI - Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules. AB - Kidney proximal tubules are resistant to hypoxic injury if glycine or L-alanine is present in their incubation medium. Protection does not depend on the concentration or turnover of ATP in cells. We have investigated structure function relationships that govern this protective activity. Among more than 45 amino acids and analogs examined, only glycine, L-alanine, D-alanine, beta alanine, and the neuronal glycine binding site agonist, 1-aminocyclopropane-1 carboxylic acid, were active. The protective effect could not be explained by amino acid metabolism. Ultrastructural features in protected cells were preserved to a degree which suggested that processes responsible for degradation during hypoxia were retarded. These results are consistent with stringent requirements of amino acid molecular structure for protection against hypoxia, and suggest the involvement of highly specific, acceptor-ligand effects on a process critical for maintaining cellular integrity. PMID- 2253850 TI - Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo. AB - To determine the role of neutrophils in the pathogenesis of hepatic ischemia/reperfusion injury, livers from male Fischer rats were subjected to 45 min of no-flow ischemia followed by reperfusion for up to 24 h. Two phases of liver injury were identified, an initial phase during the first hour of reperfusion and a later progression phase with 80 +/- 3% hepatocyte necrosis and an 80-fold increase of neutrophil infiltration in the liver after 24 h. Pretreatment with a monoclonal antibody against neutrophils, which caused consistent neutropenia, protected the liver from reperfusion injury as indicated by 28 +/- 10% necrosis, and 84% reduction of hepatic neutrophil accumulation and a complete recovery of the hepatic ATP content. Our data suggest that the later progression phase of reperfusion injury after hepatic no-flow ischemia is mediated mainly by neutrophils. PMID- 2253852 TI - Percentage of principal investigators (PIs) competing for NIH grants that are funded. PMID- 2253851 TI - Cell-surface expression of glia maturation factor beta in astrocytes. AB - Glia maturation factor beta (GMF-beta) is a 17-kDa acidic protein isolated from the brain. When added to cultured cells, GMF-beta promotes the phenotypic expression of glia and neurons and inhibits the proliferation of their respective tumors. Although astrocytes produce GMF-beta and store it inside the cells, they do not secrete the protein into the cultured medium. This poses a question as to how GMF-beta mediates intercellular communication. This paper provides an answer by demonstrating the presence of GMF-beta on the surface of astrocytes, using gold-labeled antibody enhanced with silver. It appears that cell-surface GMF-beta acts on the target cells at close range when cells are in direct contact. In contrast to astrocytes, we failed to detect GMF-beta on the surface of C6 glioma cells, although these cells, like astrocytes, possess endogenous intracellular GMF-beta and are also responsive to GMF-beta added to the medium. The lack of cell-surface expression of GMF-beta in C6 cells may reflect a breakdown in intercellular communication in these malignant cells. PMID- 2253853 TI - Young investigators. PMID- 2253854 TI - [Heterogeneity of leukemic cell phenotype. II. Variants of hetero- phenotype in relation to myeloid and megakaryocytic markers of leukemia cells in acute leukemia and blast crisis of chronic myeloproliferative disorders]. PMID- 2253855 TI - [Acute mixed-cell human leukemia]. AB - The incidence rate of acute mixed-lineal leukemias, distinguished in a group of patients with acute non-lymphoblastic leukemia, in children and adults was about the same: CALLA 10-20%, T-cell antigens 15-22%, Thy-1 15-17%. The incidence rate of acute lymphoblastic leukemia with myeloid (17-21%) and erythroid (12-13%) antigens did not significantly differ in children and adults. Distinguishing features have been proposed for actual acute mixed-lineal leukemias having markers of mature stages of varying cell line differentiation from cryptic lineal different-marker leukemias of bi- or polypotent precursor-cell origin. PMID- 2253856 TI - [Use of monoclonal antibodies in clinical oncology]. AB - Clinical possibilities of using monoclonal antibodies (MCA) in the immunodiagnosis of malignant neoplasms have been analysed. Certain Soviet and foreign MCA to tumor-associated antigens have been characterized, and their clinical importance has been estimated. A special attention has been paid to MCA against "cross", i.e. leukemia-associated, antigens. Basing on the data obtained it has been established that the use of even two MCA series (ICO-10 and ICO-20) makes available sufficiently accurate information on the tumor histogenesis. Besides that, MCA ICO-63, HNK-1, ICO-10, ICO-46 can be used for immunophenotyping of some solid tumors, particularly, for the immunophenotyping of human neuroblastoma cells. PMID- 2253857 TI - [Membrane markers and interleukin-2 receptor of splenic lymphocytes in children with aplastic anemia: detection of active subpopulations]. AB - A total of 16 children with aplastic anemia were investigated, among them 6 girls and 10 boys, the mean age 10.5 years. Splenectomy was included into the complex of treatment along with glucocorticoid and transfusion-replacement therapy of all the children. The membrane markers of splenic lymphocytes were assayed in the indirect immunofluorescence test with monoclonal antibodies of ICO and OKT series. The mean parameters did not significantly differ from those of subpopulations of splenic lymphocytes in the control group described in the literature. An individual analysis made in 8 patients (50%) has revealed active lymphocyte populations in the spleen: in the group of patients with a favourable prognosis to the disease an increase in the percent of B-cells was recorded in 2, OKT8(+)-lymphocytes in 1 patient; a rise in the percent of cells with receptors to interleukin-2 in 3 patients (from 25 to 32%); in the group of patients with severe aplasia an increase in the percent of activated HLA-DR(+)-lymphocytes was recorded in 2, and OKT8(+)-lymphocytes in 1 patient. All the patients responded well to the treatment. It has been suggested that in all cases the splenectomy effect is associated with the removal of immunoactive lymphocytes and can serve as an equivalent of the immunosuppressive therapy. The effect of splenectomy in the rest cases has been obscure. PMID- 2253858 TI - [Study of lymphocyte subpopulations using peanut, soybean and snail lectins]. AB - The method of penning in plastic dishes was to isolate the PNA+ and PNA- cell populations from the tonsil tissue. Carbohydrate determinants of lymphoid cell surface membranes being at varying stages of antigen-independent and antigen dependent differentiation have been studied with the use of peanut, soya and edible snail lectins conjugated with horse radish peroxidase. PMID- 2253859 TI - [Monoclonal antibodies BCA-B/20 against membrane antigens of human B-cells]. PMID- 2253861 TI - [B-cellular immunity]. PMID- 2253862 TI - [Ontogenesis of normal human B-lymphocytes]. PMID- 2253860 TI - [Bone marrow hematopoiesis. Evaluation of the myelogram]. PMID- 2253863 TI - [Monoclonal antibodies of the ICO series against differentiation antigens of human lymphocytes]. AB - The principal characteristics of monoclonal antibodies (MCA) ICO have been presented. The MCA ICO panel includes MCA against differentiating antigens of T- and B-lymphocytes, myelomonocytes, human leukemia-associated antigens. The following MCA have been described: MCA ICO-87 against common T-cell antigen CD7, ICO-33 and ICO-80 against common T-cell antigen CD5, MCA ICO-10 against Thy-1 antigen of early thymocytes, ICO-44 against CD1c antigen of cortical thymocytes, MCA ICO-90 against CD3 antigen of mature T-lymphocytes, MCA ICO-86 against CD4 antigen of T-helper/inductor cells, MCA ICO-31 against CD8 antigen of T suppressor/cytotoxic cells, MCA ICO-1 against nonpolymorphic antigens of HLA II class, MCA ICO-12 against CD22 antigen of B-lymphocytes, MCA ICO-30 against mu chain of human IgGM, MCA ICO-66 against CD37 antigen of B-lymphocytes, MCA ICO-88 against antigen of activated T- and B-cells, MCA ICO-35 against lymphoblasts, MCA ICO-88 against CD38 antigen of thymocytes and activated cells. PMID- 2253864 TI - [Monoclonal antibodies ICO-11 in the prognostic evaluation of acute nonlymphoblastic leukemia]. AB - The antigen detectable with monoclonal antibodies ICO-11 was studied in cells of 33 patients with acute lymphoblastic leukemia (ALL) and 47 patients with acute non-lymphoblastic leukemia (ANLL). The incidence rate of antigen-positive cases in ALL comprised 39.4%, in ANLL 35.4%. The presence of antigen in blasts in ALL did not influence the disease prognosis. The presence of ICO-11+ blasts in ANLL was characteristic of the group of patients with more favourable prognosis: a higher survival rate, due to a higher frequency of remissions, a longer life-time in the absence of remission. Basing on the clinico-hematological data ICO-11+ group could not be identified as more favourable prognostically. PMID- 2253865 TI - [Heterogeneity of leukemia cell phenotype. I. Variants of hetero- phenotype in relation to myeloid and erythrocytic markers of leukemic cells in acute leukemia and blast crisis of chronic myeloproliferative disorders]. PMID- 2253866 TI - On the asymptotic behavior of the estimate of the recombination fraction under the null hypothesis of no linkage when the model is misspecified. AB - We show that under the null hypothesis of no linkage the maximum likelihood estimator of the recombination fraction converges to 1/2 even when the trait related parameter values in the likelihood function are misspecified. Furthermore, we show that under the null hypothesis of no linkage, but with misspecified trait-related parameter values, the negative of twice the natural logarithm of the likelihood ratio statistic still has a limiting chi-square distribution with 1 degree of freedom. PMID- 2253867 TI - Search for faster methods of fitting the regressive models to quantitative traits. AB - The regressive models describe familial patterns of dependence of quantitative measures by specifying regression relationships among a person's phenotype and genotype and the phenotypes and genotypes of antecedents. When the number of sibs in the pattern of dependence increases, as in the class D regressive model, computation of the likelihood becomes time consuming, since the Elston-Stewart algorithm cannot be used generally. On the other hand, the simpler class A regressive model, which imposes a restriction on the sib-sib correlation, may lead to inference of a spurious major gene, as already observed in some instances. A simulation study is performed to explore the robustness of class A model with respect to false inference of a major gene and to search for faster methods of computing the likelihood under class D model. The class A model is not robust against the presence of a sib-sib correlation exceeding that specified by the model, unless tests on transmission probabilities are performed carefully: false detection of a major gene is reduced from a number of 26-30 to between 0 and 4 data sets out of 30 replicates after testing both the Mendelian transmission and the absence of transmission of a major effect against the general transmission model. Among various approximations of the likelihood formulation of the class D model, approximations 6 and 8 are found to work appropriately in terms of both the estimation of all parameters and hypothesis testing, for each generating model. These approximations lessen the computer time by allowing use of the Elston-Stewart algorithm. PMID- 2253868 TI - Family history of ischemic heart disease with respect to mean twin-pair cholesterol and subsequent ischemic heart disease in the NHLBI twin study. AB - This study examines the independent and interactive effects of family history scores (FHxS) for the prevalence of ischemic heart disease with plasma lipids and subsequent morbidity and mortality from ischemic heart disease. FHxS were calculated for 514 sets of middle aged male twins who participated in the entry examination of the NHLBI Veteran twin study in 1969-1973. Comparison of the FHxS with the level of plasma total cholesterol and HDL cholesterol (HDLc) paralleled earlier reported findings in young adults; individuals with high total cholesterol in two exams 8-12 years apart had significantly (P less than .01) higher FHxS. The same relationship was noted when using the mean twin-pair cholesterol level at the initial exam when the twins were in their 40s. Using the pair means over two exams as the cotwins aged into their 50s, the association of FHxS with total cholesterol declined and pairs with HDLc persistently in the highest quintile at both exams had significantly (P less than .01) lower FHxS. The changes in the pattern of association of lipid fractions with FHxS with age parallel the reported age decline of total cholesterol as a risk factor for heart disease. Assessment of ischemic heart disease events up to January 1988 revealed a highly significant association (P less than .0001) of later ischemic heart disease events with FHxS. At each level of lipid categorization pairs who later had events had higher FHxS than those without any subsequent heart disease; these differences were significant in all but the low risk lipid groups (low total cholesterol, high HDLc, and low total cholesterol/HDLc ratio). We conclude that FHxS is related to total cholesterol and HDLc but also is an independent predictor of subsequent ischemic heart disease after 14-18 years of follow-up. PMID- 2253869 TI - Note on linkage analysis when the mode of transmission is unknown. AB - A major difficulty in a linkage analysis arises from the necessity of specifying the mode of inheritance prior to analysis. For a complex disease, such as those encountered in psychiatric illnesses, the mode of inheritance is generally not known in advance. Consequently, some estimation procedure is often combined with linkage analysis to circumvent this. We discuss several precautions that should be taken when using traditional statistical testing methods: correction of the likelihood for the method of sampling families and the computation of the lod score. We analyze simulated data with pedigrees selected under a sampling scheme approximating single ascertainment. In this situation, the severity of the above problems is attenuated. PMID- 2253870 TI - Sib-pair linkage tests for disease susceptibility loci: common tests vs. the asymptotically most powerful test. AB - Several statistical tests for linkage between a disease susceptibility locus and a marker locus for sib-pair data are examined analytically. Two common statistics, a test based on the mean number of marker alleles shared identical by descent by sib-pairs, and a test based on the proportion of sib-pairs sharing exactly two marker alleles, are shown to be special cases of a more general statistic. We use this more general statistic to derive the asymptotically most powerful statistic for a given genetic alternative hypothesis, and then compare this statistic with the "mean" statistic and the "proportion" statistic. Results indicate that the "mean" statistic generally compares well with the most powerful statistic. However, in some instances the "mean" statistic may lose power, relative to the most powerful. To guard against this, a new statistic (the maximum of the "mean" and "proportions" statistics) is considered and its asymptotic distribution is derived. Results indicate that this new statistic performs well. PMID- 2253871 TI - Estimation of disease risk under bivariate models of multifactorial inheritance. AB - Adjunct consideration of both qualitative (affection status) and quantitative (correlated liability indicator) information to define a bivariate phenotype can increase considerably the accuracy and efficiency of disease risk estimation. A general approach for calculating morbid risks to offspring on the basis of parental affection status and an offspring quantitative trait is presented. We also describe two different bivariate models of multifactorial inheritance, as implemented in the computer programs POINTER and YPOINT, and make explicit their assumptions/constraints when estimating the within-person and parent-offspring correlations necessary for calculation of morbid risks. We use psychometric family data on schizophrenia from the New York High-Risk Project to estimate these correlations and illustrate our methods. Our results show that even when a trait is only moderately correlated with liability, incorporation of quantitative trait information can lead to resolution of a range of risk to offspring that is not possible through reliance on parental affection status alone. Bivariate models provide a useful methodology for incorporating quantitative indicators of liability in the investigation of genetically complex diseases. PMID- 2253872 TI - The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. PMID- 2253873 TI - MyoD family: a paradigm for development? PMID- 2253874 TI - ski can cause selective growth of skeletal muscle in transgenic mice. AB - We have created several lines of mice that contain a truncated chicken c-ski cDNA linked to an MSV LTR promoter. Adult mice from three independent lines show large increases in skeletal muscle. All three lines of mice express high levels of c ski mRNA and protein in skeletal muscle. All other tissues examined show little or no expression of the c-ski transgene. The muscles of one of the three lines were examined in more detail. Type II fast fibers undergo selective hypertrophy in affected muscles of this line. PMID- 2253875 TI - Light is required for conidiation in Aspergillus nidulans. AB - Light is necessary for asexual sporulation in Aspergillus nidulans but will elicit conidiation only if irradiation occurs during a critical period of development. We show that conidiation is induced by red light and suppressed by an immediate shift to far red light. Conidiation-specific gene functions switch from light-independent to light-dependent activities coincident with the expression of brlA, a regulator of conidiophore development. We also show that light dependence is abolished by a mutation in the velvet gene, which allows conidiation to occur in the absence of light. We propose that the initiation of late gene expression is regulated by velvet and controlled by a red light photoreceptor, whose properties are reminiscent of phytochrome-mediated responses observed in higher plants. PMID- 2253876 TI - Integration host factor is required for the activation of developmentally regulated genes in Caulobacter. AB - Several temporally controlled flagellar genes in Caulobacter crescentus require a sigma 54 promoter and upstream sites for transcription activation. We demonstrate here that in some of these genes, an AT-rich region containing an integration host factor (IHF) consensus binding site lies between the activator and the promoter, and that this region binds IHF in vitro. Analysis of mutations in the IHF-binding region of the hook operon demonstrated that an intact IHF-binding site is necessary for transcription in vivo. An adjacent and divergent promoter also has an IHF consensus sequence that binds IHF. The IHF and enhancer sites are 3' to the transcription start site in this promoter. We postulate that IHF mediates the formation of a higher order structure between the divergent promoter regions in a manner analogous to the nucleosome-like structure generated for lambda-Escherichia coli DNA recombination and that this higher order structure modulates transcription. PMID- 2253877 TI - MHC class II regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain. AB - The regulation of MHC class II gene expression controls T-cell activation and, hence, the immune response. Among the nuclear factors observed to bind to conserved DNA sequences in human leukocyte antigen (HLA) class II gene promoters, RFX is of special interest: Its binding is defective in congenital HLA class II deficiency, a disease of class II gene regulation. The cloning of an RFX cDNA has allowed us to show by transfection of a plasmid directing the synthesis of antisense RFX RNA that RFX is a class II gene regulatory factor. RFX is a novel 979-amino-acid DNA-binding protein that contains three structurally and functionally separate domains. The 91-amino-acid DNA-binding domain is distinct from other known DNA-binding motifs but may be distantly related to the helix loop-helix motif. The most striking property of RFX is that it can bind stably to the class II X box as either a monomer or a homodimer and that the domain responsible for dimerization is distant from and functionally independent of the DNA-binding domain. This distinguishes RFX from other known dimeric DNA-binding proteins. It also implies that an RFX homodimer has two potential DNA-binding sites. We therefore speculate that RFX could form a DNA loop by cross-linking the two X-box sequences found far apart upstream of MHC class II genes. PMID- 2253878 TI - LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. AB - A gene, encoding a liver-enriched transcriptional activator protein (LAP) has been isolated. LAP is a 32-kD protein that stimulates the transcription of chimeric genes containing albumin D-promoter elements both in vivo and in vitro. LAP shares extensive sequence homology (71%) in its DNA-binding and leucine zipper domains with C/EBP. As a consequence, these two proteins show an indistinguishable DNA-binding specificity and readily heterodimerize. In addition, both genes, lap and cebp, are devoid of intervening sequences. Although correctly initiated transcripts from the LAP gene accumulate in the six examined tissues--liver, lung, spleen, kidney, brain, and testis--LAP protein is highly enriched in liver nuclei. Thus, the preferential accumulation of LAP protein in liver appears to be regulated post-transcriptionally. PMID- 2253879 TI - A major positive regulatory region located far upstream of the human alpha-globin gene locus. AB - We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved. PMID- 2253880 TI - The characterization of the TFIIIA synthesized in somatic cells of Xenopus laevis. AB - In somatic cells of Xenopus, transcription of the TFIIIA gene initiates greater than 200 bp upstream from the start site used in oocytes. The resultant mRNA encodes a protein, S-TFIIIA, that is 22 amino acids longer at its amino terminus than the abundant form of TFIIIA in oocytes (O-TFIIIA). S-TFIIIA binds the 5S RNA gene and 5S RNA, and both O- and S-TFIIIA promote the formation of stable transcription complexes on oocyte-type 5S RNA genes in an oocyte nuclear extract. We have not found any functional difference between the two forms of TFIIIA. Different transcription start sites suggest differential promoter usage--one in oocytes that permits high levels of gene activity and another that is used in somatic cells for low-level TFIIIA mRNA synthesis. PMID- 2253881 TI - A TATA-like sequence located downstream of the transcription initiation site is required for expression of an RNA polymerase II transcribed gene. AB - TFIID, the TATA-binding protein, was found to stimulate transcription from the adenovirus IVa2 promoter, a promoter considered to lack the TATA motif. Remarkably, a TATA-like sequence element located downstream of the transcription start site binds TFIID and is required for TFIID-dependent transcription from the IVa2 promoter. Transcription from the IVa2 and the adjacent adenovirus major late promoter (Ad-MLP) is divergent, and the cap sites are separated by 212 nucleotides. Nevertheless, the TATA motifs of the IVa2 promoter and Ad-MLP were found to be oriented in the same direction. An initiator motif around the transcription start site is located in the IVa2 promoter, and in contrast to the TATA motifs, the IVa2-initiator is in the opposite orientation with respect to the initiator of the Ad-MLP. A model is presented in which the polar nature of the initiator governs the direction of transcription. We propose that RNA polymerase II and accessory factors recognize the initiator in an orientation dependent fashion. The recognition of the IVa2 initiator by RNA polymerase is enhanced by the binding of TFIID to the downstream TATA motif. PMID- 2253883 TI - Cloning and sequencing the gene encoding Escherichia coli ribonuclease I: exact physical mapping using the genome library. AB - The amino acid (aa) sequence of the N terminus of Escherichia coli RNase I was determined. A mixed oligodeoxynucleotide coding for that sequence was used to probe the 476 lambda clones of Kohara et al. [Cell 50 (1987) 495-508]. DNA from these clones carry almost the entire E. coli chromosome in overlapping segments. Two overlapping clones hybridized to the probe sequence. From one of them DNA containing the rna gene was subcloned and sequenced. The inferred protein contains 245 aa residues and has an Mr of 27,156, which agrees with earlier estimates from sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. RNase I is close to twice the size of pancreatic RNase A, but both enzymes contain eight Cys and four His; those aa are important for structure and function of RNase A. Proximal to the rna gene is a sequence that would code for a 23-aa peptide which conforms to consensus rules for signal peptides, and thus should transport this periplasmic enzyme. Sites for eight restriction enzymes had been mapped on each lambda clone. By relating to the map for that specific region, it was possible to position the rna gene exactly at 659 kb from the thr locus (time zero on a time scale of 100 min). This physical mapping gave a more precise (exact) map position based on distance than was possible using genetic mapping based on a time scale derived from conjugation, and should be applicable for mapping many other E. coli genes. PMID- 2253882 TI - Amino acid changes in conserved regions of the beta-subunit of Escherichia coli RNA polymerase alter transcription pausing and termination. AB - Control of transcription at pause and termination sites is common in bacteria. Many transcriptional pause and termination events are thought to occur in response to formation of an RNA hairpin in the nascent transcript. Some mutations in the beta-subunit of Escherichia coli RNA polymerase that confer resistance to the transcription inhibitor rifampicin also alter the response to transcriptional pause and termination signals. Here, we report isolation of termination-altering mutations that do not confer rifampicin resistance and show that such mutations occur predominantly in limited regions of the beta-subunit polypeptide. One region is between amino acid residues 500 and 575, which encompasses the locations of almost all known rifampicin-resistance mutations. Many termination altering mutations also occur in two other regions: between amino acid residues 740 and 840 and near the carboxyl terminus of the beta-subunit (amino acid residues 1225-1342). Amino acid sequences in these three regions of the beta subunit are conserved between prokaryotic and eukaryotic beta-subunit homologs. Several mutations that alter transcription termination in vitro affect amino acid residues that are identical in prokaryotic and eukaryotic RNA polymerase beta subunit homologs, suggesting that they alter an important function common to multisubunit RNA polymerases. We propose that these three regions of the beta subunit may contact the nascent RNA transcript, the RNA-DNA heteroduplex, or the DNA template in the transcription complex and that mutations in these regions alter transcription pausing and termination by affecting these contacts. PMID- 2253884 TI - Nitrogen regulation in Aspergillus: are two fingers better than one? AB - The areA gene, mediating nitrogen metabolite repression in Aspergillus nidulans, encodes a positive-acting regulatory protein with a single putative DNA-binding 'zinc finger' which is remarkably similar to the two 'zinc fingers' of the major regulatory protein of vertebrate erythroid cells (GF-1/Eryf1/NF-E1). The areA-300 mutation alters the specificity of gene activation in that it elevates expression of certain structural genes whilst reducing expression of certain others. It is an 'in-frame' tandem duplication of 417 bp including the entire DNA-binding region. The consequences of areA didactyly are further explored by construction of a double mutant having an altered loop residue in the N-terminal 'finger'. PMID- 2253885 TI - RleAI: a novel class-IIS restriction endonuclease from Rhizobium leguminosarum recognizing 5'-CCCACA(N)12-3' 3'-GGGTGT(N)9-5'. PMID- 2253886 TI - Construction of a promoter-probe shuttle vector for Escherichia coli and brevibacteria. AB - We constructed a promoter-probe vector, pJUP05, for brevibacteria and Escherichia coli based on the promoterless neomycin-resistance (neoR) gene from Tn5. This gene confers resistance to the aminoglycosides, kanamycin and neomycin. The promoter of the neoR gene was deleted and replaced by a suitable multiple cloning site. There are translation stop codons in all three reading frames upstream from the neoR gene. The plasmid contains functional origins of DNA replication for both brevibacteria and E. coli, and permits selection for chloramphenicol- and/or ampicillin-resistance markers. PMID- 2253887 TI - Primary structure of AfsR, a global regulatory protein for secondary metabolite formation in Streptomyces coelicolor A3(2). AB - The afsR gene of Streptomyces coelicolor A3(2) complements afsB mutations affecting production of pigmented antibiotics. It also directs pigment production in Streptomyces lividans when carried on a plasmid vector. Nucleotide sequencing of the afsR gene revealed that it codes for a 993-amino acid protein (Mr 105,600) with A- and B-type ATP-binding consensus sequences at its N-terminal portion and two DNA-binding consensus sequences with a helix-turn-helix motif at its C terminal portion. Each of the N- and C-terminal halves was capable of conferring pigment production, to some extent, in S. lividans, when carried separately on a multicopy plasmid. In addition, expression in trans of the two regions on the same plasmid conferred pigment production to almost the same extent as did the intact afsR gene. Mutations at the two ATP-binding consensus sequences, that were generated by in vitro site-directed mutagenesis, revealed their functional importance. Disruption of the S. coelicolor A3(2) chromosomal afsR gene in either the N- or C-terminal half using phage phi C31 KC515 resulted in significant, but not complete, loss of pigment production. These data suggest that the AfsR protein comprises two domains, viz., an ATP-binding and a DNA-binding domain, each of which could function as a positive regulator for pigment production. These afsR mutants sporulate normally. In addition to an internal promoter, which we previously detected in the middle of the AfsR coding region, S1 nuclease mapping revealed two tandem transcriptional start points, separated by 64 bp, upstream from a putative ATG start codon of the AfsR product. PMID- 2253888 TI - Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation, characterization and regulation of the SPO7 sporulation gene. AB - SPO7 is one of several previously identified genes from the yeast Saccharomyces cerevisiae that is required for sporulation but not for vegetative growth. The SPO7 gene has been cloned by functional complementation and physically mapped 15 16 kb to the left of CEN1. Gene-disruption experiments confirmed that the cloned gene was the bona fide SPO7 gene. SPO7 codes for a 0.95-kb transcript that is expressed at approximately the same level in both vegetative and sporulating cells. The gene was sequenced and has the capacity to encode a 259-amino acid protein that does not appear to be related to other known proteins. PMID- 2253889 TI - Single-strand-binding factor(s) which interact with ARS1 of Saccharomyces cerevisiae. AB - Since plasmids containing autonomously replicating sequence(s) (ARS) can transform Saccharomyces cerevisiae cells at high frequency, ARS are considered to be the replication origins of chromosomes. To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors which interact with the ARS1 region located near the centromere of chromosome IV in S. cerevisiae. Using the gel-shift assay, we found protein factors which bound to a single-stranded, 97-bp fragment of the ARS1 region containing the core consensus. Competition experiments with various oligodeoxyribonucleotides (oligos) suggest that a site recognized by the factor(s) was within the element containing the core consensus and adjacent close matches to the core consensus of the minus strand. Indeed, when the oligo containing the minus strand of this element was used as a probe, two oligo-protein complexes were detected. Mutations in the core consensus reduced these binding activities. When the plus-strand oligo of the same region was used as a probe, a retarded band was also detected, but with less specific binding. Considering the fact that the core consensus and close matches to the core consensus are important for ARS function, these results imply that the protein factors detected in this experiment may participate in DNA replication. PMID- 2253890 TI - The ADE2 gene from Saccharomyces cerevisiae: sequence and new vectors. AB - We have determined the sequence of a DNA fragment encoding the ADE2 gene from Saccharomyces cerevisiae. A DNA fragment of 2241 bp capable of complementing ade2 mutations was modified so it is available as a single BglII fragment for use in yeast vectors or for gene disruptions. The minimal fragment codes for a putative protein which is highly similar to the protein encoded by the ADE6 gene from Schizosaccharomyces pombe and to the proteins encoded by the purEK operon of Escherichia coli. PMID- 2253891 TI - Will the baby boomers go bust? PMID- 2253892 TI - Ergoloid mesylates vs. Alzheimer's: the latest round. PMID- 2253893 TI - From disease to delirium: managing the declining elderly patient. AB - Many geriatric patients have concurrent physical and psychiatric illnesses, but at times it may be difficult to determine which is primary. Delirium, a transient syndrome that presents with psychiatric symptoms, is usually the manifestation of an organic disorder and, if undetected and untreated, can be fatal. Clinicians, therefore, must learn to recognize the syndrome, search diligently for the underlying etiology, and treat accordingly. PMID- 2253894 TI - Minimizing urinary incontinence in the nursing home. AB - In the nursing home, urinary incontinence is a common problem that all too often is treated as an irremediable "problem of aging" by physicians, nurses, and patients. Its etiologies are numerous, as are approaches to treatment in this setting. However, with a thoughtful approach to diagnosis and care, the primary care physician may be able to determine which patients, with which forms of urinary incontinence, will benefit from specific therapies. PMID- 2253895 TI - Anorexia in older patients: its meaning and management. AB - In the elderly, clinically significant weight loss is closely related to malnutrition, the causes of which can proliferate in this age group. Clinicians must therefore keep a wide range of possible etiologies in mind when evaluating these patients. These fall into the general categories of social, psychological, medical, and age-related. Isolating the cause will direct what is often simple, effective, and, perhaps, life-saving therapy. PMID- 2253896 TI - How not to practice geriatrics. AB - They're slow, they're hard-of-hearing, they don't get better--elderly patients can be a pain in the practice. Here's how to keep them away. PMID- 2253897 TI - Strange days indeed: my life as a 'geriatrician'. PMID- 2253898 TI - Hypothesis that the acidification of a tissue which takes place during ischemia can lead to tissue hyperoxia during reperfusion due to the Bohr effect. PMID- 2253899 TI - Inhibition of liver microsomal lipid peroxidation by 13-cis-retinoic acid. AB - The effects of 13-cis-retinoic acid on iron/ascorbate-dependent lipid peroxidation were investigated with rat liver microsomes. 13-cis-retinoic acid effectively inhibited malondialdehyde generation and molecular oxygen consumption associated with lipid peroxidation. Under the conditions employed, inhibition was complete at concentrations as low as 25 microM and the IC50 was 10 microM. Evidence for concomitant retinoid oxidation by microsomal unsaturated fatty acid derived peroxyl radicals was demonstrated by detection of several retinoid derived metabolites, including 5,8-oxy-13-cis-retinoic acid, generated during lipid peroxidation. The data indicate that 13-cis-retinoic acid inhibits lipid peroxidation by scavenging lipid peroxyl radicals with its conjugated polyene system. Its antioxidant properties may contribute to the pharmacological activities of this and related retinoids. PMID- 2253900 TI - Expression of bovine and mouse endothelial cell antioxidant enzymes following TNF alpha exposure. AB - Endothelial cells are primary targets for injury by reactive oxygen species. Endothelial catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganous superoxide dismutase (MnSOD) provide potential antioxidant enzymatic defenses against oxidant-induced cellular damage. Previous studies in vivo and in vitro have demonstrated that in certain cell types exposure to oxidants may increase the expression of one or more of these antioxidant enzymes, thus providing greater intracellular potential to withstand oxidant-induced cell stress. To test whether endothelial antioxidant enzyme expression is influenced by similar oxidant-induced stresses in vitro, we have exposed endothelial cells to tumor necrosis factor-alpha (TNF-alpha) and have measured levels of catalase, CuZnSOD and MnSOD mRNA, and protein. Our results demonstrate a selective increase of MnSOD mRNA, with coordinate increases of both MnSOD protein and enzyme activity in endothelial cells treated for 24/h with TNF-alpha. In contrast, levels of catalase and CuZnSOD mRNA and protein remained unchanged in these cells after TNF alpha treatment. These observations were made in microvessel endothelial cells derived from murine and bovine sources. Our results indicate that TNF-alpha can act specifically to increase enzymatic antioxidant potential in endothelial cells by induction of a particular antioxidant enzyme encoding mRNA species. These data demonstrate the capacity of endothelial cells to mount an antioxidant defense in response to exposure to an inducer of oxidative damage. PMID- 2253901 TI - Carcinoma of the gastric stump: risks and pathogenesis. PMID- 2253902 TI - Bulimia nervosa and a stepped care approach to management. PMID- 2253903 TI - Effect of incorporating fat into a liquid test meal on the relation between intragastric distribution and gastric emptying in human volunteers. AB - The relation between gastric emptying and the intragastric distribution of 300 ml radiolabelled beef consomme with and without 60 g margarine was investigated by performing randomised, paired gammacamera studies in seven healthy male volunteers (aged 20-22 years). The low calorie bland meal emptied rapidly from both the proximal and distal stomach after a short lag period (4-6 min), during which 24-50% of the liquid passed into the distal stomach. Addition of margarine to the liquid test meal increased the lag period (median 32 min, range 7-60 min; p less than 0.01) and decreased the slope of emptying (T1/2 lag period 88 min, 49 146 min v 15 min, 10-57 min; p less than 0.01). During the lag period there was an initial filling of the distal stomach, similar to that with the bland liquid, followed by a redistribution of between 19% and 61% (median 46%) of the distal stomach contents back into the proximal stomach. At the onset of emptying, the distal stomach filled (median 30%, range 16-34%) and during this time the proximal stomach emptied twice as fast as the whole stomach (p less than 0.05). Thereafter, the distal stomach capacity remained relatively constant while both the proximal and whole stomach emptied at similar rates. This study shows that the delay in gastric emptying of a liquid that has a high fat content is due in part to a redistribution of distal stomach contents back into the proximal stomach. PMID- 2253904 TI - Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum. AB - The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa. PMID- 2253906 TI - Paf-acether synthesis by Helicobacter pylori. AB - Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa. PMID- 2253905 TI - Evaluation of 13C-urea breath test in the detection of Helicobacter pylori and in monitoring the effect of tripotassium dicitratobismuthate in non-ulcer dyspepsia. AB - Sixty nine patients with non-ulcer dyspepsia have been studied with endoscopy, biopsy, quick urease (CLO) test, Helicobacter pylori culture, and the 13C-urea breath test before and after treatment with tripotassium dicitratobismuthane (DeNol) two tablets twice daily for four weeks. Symptoms of non-ulcer dyspepsia were recorded using a standard questionnaire. Using H pylori culture as the gold standard, the sensitivity of the 13C-urea breath test was 90%, the specificity 98.6%, and the accuracy 94.8% with a positive predictive value of 98.2% and a negative predictive value of 92.5%. Conversion rate from H pylori positive to negative status after treatment with tripotassium dicitratobismuthate was 17.9%. Symptoms of non-ulcer dyspepsia improved appreciably after treatment irrespective of H pylori status. The 13C-urea breath test is an accurate research tool suitable for serial testing and population surveys. PMID- 2253907 TI - Use of automatic computerised pump to maintain constant intragastric pH. AB - We used continuous variable rate infusions of famotidine in eight normal volunteers under fasting conditions to raise intragastric pH to 5.0. An intragastric glass electrode continuously monitored acidity and this information was automatically computed to regulate an intravenous infusion system (GastroJet). The computer was programmed to aim for pH 6.0, increasing and lowering infusion rates accordingly. Two regimens were compared with placebo (10 mg bolus followed by infusion or infusion of famotidine alone). Volunteers were admitted to an investigation ward and each study was preceded by a standard normal meal. Hydration was maintained with intravenous fluids. During placebo treatment the median pH was 1.5 and the pH was less than 5.0 for 98% of the time. All volunteers responded to famotidine but dosage requirements varied (range 41 mg to 126 mg). The median pH rose to 6.5 when infusions of famotidine followed boluses and to 6.6 when infusions alone were used - the pH was less than 5.0 for 20% and 16% of the time respectively (p less than 0.05 Wilcoxon compared with placebo). Mean drug use was greater with boluses (98 mg v 87 mg p = 0.03: paired Student's t test) and onset was not apparently faster. Blood famotidine concentrations followed infusion rate changes. Famotidine infused by GastroJet maintains a high fasting intragastric pH and priming boluses are probably unnecessary. PMID- 2253908 TI - Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue: an immunohistochemical study. AB - Immunohistochemical distributions of cathepsins D and E were determined in normal mucosa, metaplastic, dysplastic, and cancerous lesions of the human stomach. Cathepsins D and E were localised in the foveolar epithelium and parietal cells of the normal gastric mucosa, but their intracytoplasmic distributions were different - cathepsin E distribution was even and diffuse in the cytoplasm while cathepsin D was found in coarse intracytoplasmic granules. Chronic inflammation and ulcer did not influence the distribution of these enzymes. No positive staining was obtained in the incomplete type of intestinal metaplasia, dysplasia, and well differentiated adenocarcinoma. Tumour cells of signet ring cell carcinoma and poorly differentiated adenocarcinoma cells, however, gave strong and diffuse stainings for cathepsins D and E in the cytoplasm. The results suggest that the distribution of cathepsins D and E is related to each specialised function of the foveolar epithelium and the parietal cells, and that their disappearance is associated with development of well differentiated adenocarcinoma from intestinal metaplasia. PMID- 2253909 TI - Modulation of fluid absorption and the secretory response of rat jejunum to cholera toxin by dietary fat. AB - To study the effects of dietary fat on jejunal water and ion absorption and on cholera toxin-induced secretion, 3 week old Sprague Dawley rats were fed isocaloric diets. Forty per cent of the total calories were given as fat, as butter (high saturated fat), olive oil (high monounsaturated fat), or corn oil (high polyunsaturated fat), with one group on low fat (10% of calories) standard laboratory diet as controls. During in vivo jejunal perfusion studies we found that (i) a polyunsaturated fat (corn oil) supplemented diet improves jejunal absorption of water and electrolytes and these changes are independent of the observed concentrations of luminal prostaglandins; (ii) high dietary fat appreciably reduced the secretory response to cholera toxin, probably without fundamentally changing the mechanism by which cholera toxin induces secretion. We conclude that dietary fat composition altered the permeability and transport characteristics of the small intestine. This observation might have relevance to some human diarrhoeal disorders. PMID- 2253910 TI - Crohn's disease in the city of Derby, 1951-85. AB - An epidemiological survey of Crohn's disease in the city of Derby showed that the incidence of the condition increased from 0.7/10(5) per year between 1951 and 1955 to 6.67/10(5) per year between 1981 and 1985 but seemed to reach a plateau between 1976 and 1985. Large bowel Crohn's disease was more common in patients presenting aged 60-79 years than in those aged 20-39 years. The increase in incidence was not solely due to the detection of milder disease. There was no evidence that the Asian (Indian subcontinent) population of Derby was resistant to the development of Crohn's disease. PMID- 2253911 TI - Microspectrophotometric DNA analysis in ulcerative colitis with special reference to its application in diagnosis of carcinoma and dysplasia. AB - The deoxyribonucleic (DNA) content was measured by microspectrophotometry in 100 specimens from 60 patients with ulcerative colitis, including six patients in whom the colitis was associated with carcinoma. Some 23 of 30 (77%) specimens of dysplastic tissue showed aneuploidy or polyploidy, whereas 50 of 53 (94%) specimens of non-dysplastic tissue showed diploidy. The difference was statistically significant (p less than 0.001). Polyploidy was often observed in non-dysplastic mucosa from patients who had carcinoma or dysplasia. In the non dysplastic patients all samples of inflamed tissue showed diploidy. Some 10% of samples without inflammation, however, also showed polyploidy. A good correlation was found between the frequency of polyploid cells and the grade of dysplasia. Microspectrophotometric measurement of DNA content proved useful in the assessment and diagnosis of dysplasia in ulcerative colitis and could be considered for screening high risk patients. PMID- 2253912 TI - Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. AB - To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5 aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment. PMID- 2253913 TI - Evidence for motor neuropathy and reduced filling of the rectum in chronic intractable constipation. AB - Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum. PMID- 2253914 TI - Concordance between colonic myoelectrical signals recorded with intramuscular electrodes in the human rectosigmoid in vivo. AB - The myoelectrical activity of the human rectosigmoid colon was studied simultaneously in six subjects at two sites using two pairs of fine wire bipolar electrodes. The electrodes were spaced 2-5 cm apart in the rectosigmoid after insertion into the smooth muscle layers under direct vision at sigmoidoscopy. The electrodes were implanted at positions between 8 and 25 cm from the anal verge in different subjects. The frequency of myoelectrical burst activity together with the burst duration recorded by each electrode pair was examined. The relation of burst frequency and burst duration in the higher and lower placed electrodes was also assessed. In none of the subjects was three evidence of synchrony between the electrode pairs. In addition, there was no relation between the relative position of the electrodes and the intrinsic frequency of duration of myoelectrical bursts. It is concluded that regions of smooth muscle in the unstimulated human colon in vivo act independently and that there is no effective common neuromuscular drive under these conditions. PMID- 2253915 TI - Role of upper gastrointestinal investigations in a screening study for colorectal neoplasia. AB - Should patients with positive faecal occult blood screening tests who are free of colorectal neoplasia undergo upper gastrointestinal investigation? Altogether 16,985 faecal occult blood tests were completed in a group of 18,818 asymptomatic patients (45-75 years) offered screening at two yearly intervals. A total of 447 (2.6%) were positive and underwent large bowel investigations. No neoplastic disease was identified in 283 (63%) of them. Fourteen (5%) also underwent gastroscopy for upper gastrointestinal symptoms, benign conditions were identified in five and a gastric carcinoma in one. No further investigations were instituted in the remaining 269 subjects who have now been followed up for a median period of 5 years (2-8 years). Five have been referred for benign upper gastrointestinal conditions, but none for upper gastrointestinal malignancy. Thirty one subjects have died - one from gastric cancer (a patient who had undergone a previous partial gastrectomy for a duodenal ulcer and who had persistent upper gastrointestinal symptoms). The remaining deaths were unrelated to the upper gastrointestinal tract. Nineteen people who have left the trial area have been monitored for the development of malignant disease; none have presented with upper gastrointestinal malignancy. These data support the view that upper gastrointestinal investigations need not be performed routinely in this group of subjects, but may be reserved for those with relevant symptoms. PMID- 2253916 TI - Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding. AB - Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy. PMID- 2253917 TI - Effect of secretin on portal venous flow. AB - In this study we evaluated the effect of two different doses of secretin on portal haemodynamics (by pulsed Doppler associated with real time ultrasound) in 24 healthy humans. In 12 subjects (group A) we administered an intravenous dose of 75 clinical units of secretin and in the remaining 12 (group B) a dose of 20 CU. In all subjects the following parameters were studied before, during, and for 10 minutes after secretin administration: (a) calibre of the portal vein, (b) mean velocity of portal venous flow, and (c) volume of portal venous flow. In three subjects in each group we also evaluated the changes in flow in the superior mesenteric artery. Secretin injection induced a slight increase in both groups in comparison to basal values of portal vein calibre (mean of maximal per cent increase +25% in group A, not significant, and +16.7% in group B, not significant) and a noticeable increase of mean velocity (mean of maximal per cent increases +61.4% in group A, p less than 0.005, and +65.4% in group B, p less than 0.01) and flow volume (mean of maximal per cent increase +127% group A, p less than 0.005, and +114% group B, p less than 0.005). The magnitude of the haemodynamic changes did not differ significantly between the two groups. Doppler investigation of the superior mesenteric artery showed a marked increase of flow velocity (mean of maximal per cent increase +218% in group A and +246% in group B) and flow volume (mean of maximal per cent increase +276% in group A and +311% in group B). These data suggest that secretin has an appreciable vasoactive effect and induces a significant increase in portal venous flow even at doses much lower than those necessary for a maximal stimulation of exocrine pancreatic secretion. PMID- 2253918 TI - Lipid peroxidation and hepatic antioxidants in alcoholic liver disease. AB - The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation. PMID- 2253919 TI - Pancreatic secretory trypsin inhibitor in gastrointestinal mucosa and gastric juice. AB - We studied the distribution of pancreatic secretory trypsin inhibitor (PSTI) in the epithelia of the gastrointestinal tract and determined whether PSTI is secreted into gastric juice. PSTI was measured by a specific radioimmunoassay in biopsy specimens taken from the upper (n = 8) and lower (n = 7) gastrointestinal tract of patients with normal endoscopies. PSTI was present in the stomach, small intestine, and colon. Concentrations (micrograms/g protein) were highest in the stomach, and significantly higher in the antrum (1240, 670-1700, median and range) than in the gastric body (370, 350-570) (p less than 0.01). Concentrations were similar in the duodenum (180, 80-210) and colon (160, 130-360). PSTI determined by immunohistochemistry was present in mucus secreting gastric foveolar cells, duodenal Paneth cells, and colonic non mucus cells. PSTI was present in gastric juice. The median (range) concentration of PSTI in basal gastric juice from 13 patients with duodenal ulcers was 9 (3-21) micrograms/l and did not change during stimulation with pentagastrin. The rate of secretion, however, did increase significantly (p less than 0.05) from 1430 (180-2810) ng/h to 4500 (1250-12,770) ng/h during pentagastrin stimulation. PSTI was labile in acid pepsin but stable in the neutral conditions present in the mucus layer. The presence of pancreatic secretory trypsin inhibitor throughout the gut and its secretion into the lumen suggests a hitherto unrecognised mechanism protecting gastrointestinal epithelia against luminal proteases. PMID- 2253920 TI - Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test. AB - The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration. PMID- 2253921 TI - Stomal adenocarcinoma in Crohn's disease. AB - Malignant change occurring at the site of a stoma in two patients with proved Crohn's disease is described. Patients with ulcerative colitis have an increased risk of colonic malignancy and Crohn's disease is also associated with both small and large bowel carcinoma. Most previous reports of stomal carcinoma have been associated with ulcerative colitis although Crohn's disease seems to carry a greater risk of associated small bowel carcinomas. This is the first report of stomal carcinoma complicating Crohn's disease. Epithelial dysplasia is associated with gastrointestinal carcinomas in both ulcerative colitis and Crohn's disease and a dysplasia-carcinoma sequence has been suggested as the origin of these tumours. In both our patients with stomal adenocarcinoma, dysplasia was identified in adjacent tissues, which suggests a similar mechanism. Malignant change should be suspected if epithelial dysplasia is discovered in a biopsy specimen from the mucosa of an ileostomy in Crohn's disease, and this risk is increased if the dysplasia is of a high grade. PMID- 2253922 TI - Squamous carcinoma in the liver. AB - Squamous carcinoma of the liver has only rarely been reported. We present a case which highlights not only the difficulties in diagnosis but also how it can closely mimic sclerosing cholangitis. PMID- 2253923 TI - Coeliac ganglionectomy. PMID- 2253924 TI - Focal nodular hyperplasia of the liver. PMID- 2253925 TI - A case of nodular regenerative hyperplasia of the liver, CREST syndrome, and primary biliary cirrhosis. PMID- 2253926 TI - Intraperitoneal administration of the biological response modifier OK-432 and peritoneal recurrence following gastrectomy. AB - In patients with gastric cancer invading the serosa, there is often peritoneal dissemination. In an attempt to control such peritoneal recurrences, OK-432, a compound composed of penicillin G-treated, attenuated Streptococcus pyogens of human origin, was administered intraperitoneally at the time of gastrectomy. The non-specific antitumor activity of the peritoneal macrophages was investigated for its cytostatic activity against the cultured human lung cancer cell line, QG 90. OK-432 given intraperitoneally significantly increased the number of the peritoneal macrophages (p less than 0.05), and also enhanced the cytostatic activity (p less than 0.01). On the basis of these findings, OK-432 IP after gastrectomy was given to 13 of 68 patients with gastric cancer invading the serosa and who underwent curative resection. The five-year survival rate of patients given the drug was 63.5%, while the rate was 52.9% in those not given the drug. OK-432 IP seemed to be effective when lymph node involvement was nil or limited to around the area of the stomach. The peritoneal recurrence rate was, however, not affected by OK-432 IP. Elevation of body temperature and some dehydration were the only observed side effects of OK-432. In attempts to control peritoneal recurrences in patients with gastric cancer invading the serosa, randomized controlled trials on OK-432 IP are now being designed. PMID- 2253927 TI - The efficacy of furazolidone and metronidazole in the treatment of chronic gastritis associated with Helicobacter (Campylobacter) pylori--a randomized double-blind placebo-controlled clinical trial. AB - Seventy-two patients with Helicobacter pylori-associated chronic gastritis were randomized to a 3-week oral treatment with furazolidone 0.1g t.i.d. or metronidazole 0.2g t.i.d. or placebo. Endoscopy was performed before and after treatment, and biopsy specimens were taken from the antrum of the stomach for histological examination and culture of Helicobacter pylori. Disappearance rates of Helicobacter pylori in furazolidone, metronidazole and the control groups were 74% (20/27) if considering completion of therapy, the 20/25 or 80%, 33.3% (8/24) and 14.3% (3/21) respectively. There was a significant difference in the disappearance rate of Helicobacter pylori between furazolidone and metronidazole, and between furazolidone and the placebo group (p less than 0.01), but there was no such difference between metronidazole and the placebo group (p greater than 0.05). In the patients receiving furazolidone, the eradication of Helicobacter pylori was accompanied by marked improvement in both inflammatory infiltration in the gastric mucosa and symptoms. These results reasonably suggest that Helicobacter pylori may play an etiological role in the pathogenesis of chronic gastritis, and that furazolidone is effective in the treatment of Helicobacter pylori-associated chronic gastritis. PMID- 2253928 TI - Mesenteric vein thrombosis, non-invasive diagnosis and follow-up (US + MRI), and non-invasive therapy by streptokinase and anticoagulants. AB - We report on the case of a young lady on oral contraceptives for only 1 month who experienced severe central abdominal pain of a progressive nature. Mesenteric vein thrombosis was diagnosed by ultrasound and confirmed by magnetic resonance imaging. The patient was treated initially with streptokinase followed by heparin and warfarin with subjective improvement, and gradual disappearance of the thrombus was observed on ultrasound and magnetic resonance imaging. In this report we wish to emphasize the feasibility of the early diagnosis of mesenteric vein thrombosis by ultrasound and magnetic resonance imaging, and the effectiveness of early thrombolytic therapy without the need for surgical intervention. PMID- 2253929 TI - Biliary lipids and bile acid composition before and after endoscopic sphincterotomy. AB - The effect induced by endoscopic sphincterotomy on biliary lipids and bile acid composition was examined by following up the seven patients prior to early (1-2 week) and late (0.5-1 year) after the endoscopic sphincterotomy. The concentrations of total bile acids, phospholipid and cholesterol were essentially constant throughout the one-year observation period. Cholesterol saturation indices were not significantly altered. No bile acid concentration changed significantly. The results indicate that endoscopic sphincterotomy has little undesirable effect on the biliary lipids and bile acid compositions over an observed period. PMID- 2253930 TI - Relationship between ras oncogene expression and clinical and pathological features of colonic carcinoma. AB - In order to investigate the value of ras oncogene expression as a prognostic indicator in colonic adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 109 surgical specimens resected at our institution between 1978 and 1981. Pathology slides and archived paraffin blocks were retrieved for confirmation of the original diagnosis, determination of stage, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody given definitive staining using the Avidin-Biotin peroxidase method. The analysis indicated that tumors with high (greater than or equal to 1:40,000) p21 titer had a lower five-year survival rate than tumors with low (less than 1:40,000) titers (34.3% vs 60.8%, p less than 0.02). When a logistic regression analysis was used with the dependent variable being five-year survival and the independent variables being age, sex, location of tumor. Dukes' stage, mucin production, p21 titer, differentiation degree and tumor size, the statistically significant relationship of the level of ras gene protein product to long-term survival was negated by the concomitant knowledge of Dukes' stage. On the other hand, when only the variables available in the preoperative period were entered in the multivariate analysis, p21 titers retained a significant relationship with long-term survival (p less than 0.05). We conclude that ras oncogene determination in colonic carcinomas may have clinical importance for the pre-operative identification of a group of colonic tumors with a more aggressive behavior and a poorer prognosis. PMID- 2253931 TI - Lactitol in the treatment of chronic hepatic encephalopathy--a randomized cross over comparison with lactulose. AB - The effect of lactitol, a new non-absorbable disaccharide, in the treatment of chronic hepatic encephalopathy was assessed in 14 cirrhotic patients with non selective portosystemic anastomosis in a randomized, cross-over study. At the time of inclusion, all patients showed alterations in mental state, and/or psychometric performance, and in the electroencephalogram. Moreover, 10 out of 14 patients suffered from recurrent episodes of hepatic encephalopathy in the 12 months prior to the study. Patients were randomly treated for two consecutive periods of six months with either lactitol or lactulose. The PSE index was calculated to quantify the neuro-psychiatric impairment. Twelve patients completed the study. The patients required a daily dose of 38.2 g +/- 19 of lactulose or 36.3 g +/- 5 of lactitol to produce two semi-soft stools per day. No deterioration in the mental state or in the other neuro-psychiatric parameters were observed, neither during lactitol nor during lactulose therapy. During the study, mild episodes of recurrent encephalopathy occurred in 60% of the patients taking lactulose, and in 25% of the patients taking lactitol, the difference not being significant (X = 1.54, p = 0.21). Flatulence, the major side-effect noted during the study, was present in 7 of the 12 patients during lactulose treatment, and in 2 patients during lactitol treatment; one patient on lactitol complained of nausea. The side effects which occurred during lactitol of the dosage, while those occurring during lactitol appeared when the dosage was higher than 40 g. Lactitol may be considered at least as effective as lactulose in the treatment of chronic hepatic encephalopathy. PMID- 2253932 TI - Portal venous gas in a patient with diverticulitis. AB - Gas in the portal vein is a rare finding associated with a grave prognosis. We present a case of portal venous gas in a 34-year-old man with an abscess due to perforated-sigmoid diverticulitis and Escherichia coli sepsis. successfully treated with sigmoid resection and antibiotic therapy. PMID- 2253933 TI - From the archives of hepato-biliary and pancreatic disease--Francis Glisson's Anatomy of the Liver and Biliary Tract. PMID- 2253934 TI - Crossover in a Spanish cystic fibrosis family. PMID- 2253935 TI - R-banding and nonisotopic in situ hybridization: precise localization of the human type II collagen gene (COL2A1). AB - A new mapping system, based on nonisotopic in situ hybridization combined with fluorescent staining of replicated prometaphase R-bands, is described. Replication of the bands is achieved by treatment of thymidine-synchronized cells with bromodeoxyuridine. The human COL2A1 gene was mapped to band 12q13.11-q13.12 in this manner, to illustrate the potential of the technique for improving the precision of chromosomal mapping and physical ordering of genes. PMID- 2253936 TI - Cytogenetic analysis of 400 sperm from three translocation heterozygotes. AB - Sperm chromosome complements were studied in three men who carried reciprocal translocations. A total of 400 sperm were karyotyped after in vitro penetration of hamster eggs: 217 sperm from t(2;9) (q21;p22), 164 from t(4;6)(q28;p23) and 19 from t(7;14) (q21;q13). All possible 2:2 and 3:1 meiotic segregations were observed for t(2;9) and t(4;6); for t(7;14) only 2:2 segregations were observed. For alternate segregations, the number of normal sperm was not significantly different from the number of sperm carrying a balanced form of the translocation in any of the translocations, as theoretically expected. The percentage of sperm with an unbalanced form of the translocation was 57% for t(2;9), 54% for t(4;6) and 47% for t(7;14). There was no evidence for an interchromosomal effect in any of the translocations since the frequencies of numerical abnormalities (unrelated to the translocation) were within the normal range of control donors. The frequencies of X- and Y-bearing sperm did not differ significantly from 50%. Results from a total of 17 reciprocal translocations studied by sperm chromosomal analysis were reviewed. PMID- 2253937 TI - Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. AB - We describe oligonucleotide primer sequences that can be used to amplify eight exons plus the muscle promoter of the dystrophin gene in a single multiplex polymerase chain reaction (PCR). When used in conjunction with an existing primer set, these two multiplex reactions detect about 98% of deletions in patients with Duchenne or Becker muscular dystrophy (DMD, BMD). Furthermore, these primers amplify most of the exons in the deletion prone "hot spot" region around exons 44 to 53, allowing determination of deletion endpoints and prediction of mutational effects on the translational reading frame. Thus, use of these PCR-based assays will allow deletion detection and prenatal diagnosis for most DMD/BMD patients in a fraction of the time required for Southern blot analysis. PMID- 2253938 TI - Genetic heterogeneity at the glucose-6-phosphate dehydrogenase locus in southern Italy: a study on a population from the Matera district. AB - Glucose-6-phosphate dehydrogenase (G6PD) has been analyzed by gel electrophoresis and by quantitative assay in an unselected sample of 1524 schoolboys from the province of Matera (Lucania) in southern Italy. We have identified 43 subjects with a G6PD variant. Of these, 31 had severe G6PD deficiency, nine had mild to moderate deficiency, and three had a non-deficient electrophoretic variant. The overall rate of G6PD deficiency was 2.6%. The frequency of G6PD deficiency, ranging from 7.2% on the Ionian Coast to zero on the eastern side of the Lucanian Apennines, appears to be inversely related to the distance of each town examined from the Ionian Coast, suggesting that this geographic distribution may reflect, at least in part, gene flow from Greek settlers. Biochemical characterization has shown that most of the G6PD deficiency in this population is accounted for by G6PD Mediterranean. In addition, we have found several examples of two other known polymorphic variants (G6PD Cagliari and G6PD A-); three new polymorphic variants, G6PD Metaponto (class III), G6PD Montalbano (class III), and G6PD Pisticci (class IV); and two sporadic variants, G6PD Tursi (class III) and G6PD Ferrandina (class II). These data provide further evidence for the marked genetic heterogeneity of G6PD deficiency within a relatively narrow geographic area and they prove the presence in the Italian peninsula of a gene (GdA-) regarded as characteristically African. PMID- 2253939 TI - The human VAV proto-oncogene maps to chromosome region 19p12----19p13.2. AB - A novel human oncogene, designated VAV, has been recently characterized. This oncogene was generated by a rearrangement within the 5' coding sequences of a normal cellular gene, the VAV proto-oncogene. The normal VAV gene is specifically expressed in hematopoietic cells regardless of their differentiation lineage. We now report that the VAV locus has been localized in the human genome at chromosome 19p12----19p13.2 by analysis of its segregation pattern in rodent human somatic cell hybrids and by chromosomal in situ hybridization. The VAV locus might be closely linked to the insulin receptor (INSR) locus, as suggested by comigration of INSR and VAV high-molecular-weight DNA fragments after pulsed field gel electrophoresis. The VAV chromosomal assignment is of interest because chromosome region 19p13 is involved in different karyotypic abnormalities in a variety of malignancies including melanomas and leukemias. The identification of a novel proto-oncogene that maps to that region will enable us to define whether VAV is involved in any of the translocations observed. PMID- 2253940 TI - Identification of functioning sweat pores and visualization of skin temperature patterns in X-linked hypohidrotic ectodermal dysplasia by whole body thermography. AB - In this preliminary study, non-invasive infrared thermography has been used to visualize individual sweat pores and whole body skin temperature patterns in subjects with X-linked hypohidrotic ectodermal dysplasia (XHED) and normal controls. The findings in eight obligate heterozygotes and four affected males were compared to six normal female controls and to six non-manifesting females at risk for carrier status. Sweat secretion from individual pores in circumscribed areas was imaged using a high spatial resolution SPRITE infrared detector system working in the 8-14 microns band. In seven out of eight obligate heterozygotes, skin areas devoid of active sweat glands were found on the face, the hands or the trunk. Tear front movement over the cornea was also visualized and abnormal patterns were identified in obligate heterozygotes. Whole body skin temperature patterns, obtained with an Agema 780 Medical Thermovision system, identified abnormal skin temperature distributions, including characteristic aberrant "cascade" back patterns, in obligate carriers. Two out of six "at risk" females had skin temperature patterns comparable with obligate heterozygotes and we have tentatively concluded that they are carriers. Thermal imaging may be used for the examination of "at risk" non-manifesting females in families with a single affected male. The results of this study suggest that the random X-inactivation in females with XHED, as well as producing relatively large skin areas with sweat pore aplasia, is also associated with abnormal temperature patterns that are consistent with altered peripheral vascular perfusion. PMID- 2253941 TI - The human corticosteroid binding globulin gene is located on chromosome 14q31 q32.1 near two other serine protease inhibitor genes. AB - Human corticosteroid binding globulin (CBG) cDNA fragments were radiolabeled and hybridized in situ to metaphase chromosome preparations. The results localized the CBG gene to the q31-q32.1 region of human chromosome 14. This location also contains the genes for two closely related serine protease inhibitors: alpha 1 proteinase inhibitor and alpha 1-antichymotrypsin. It is therefore likely that these genes evolved by duplication events, and it would appear that this region contains a series of functionally related genes. PMID- 2253942 TI - Neither age nor sex influence the expression of folate sensitive common fragile sites on human chromosomes. AB - The expression of folate sensitive common fragile sites was investigated in 82 normal healthy males and females of various ages. In 100 studied metaphases of each of these controls, between 0 and 56 lesions were detected (mean 18.3 +/- 10.3 SD). No significant difference was found between the mean number of expressed lesions in females and males. No age-effects were observed. Two "new" common fragile sites were discovered at 6p21 and 17q21. Their fragile site status, however, needs to be confirmed. PMID- 2253944 TI - Maternal transmission of ring chromosome 21. AB - A psychomotor-retarded infant with minor dysmorphic signs and a karyotype 46,XY,r(21)mat in lymphocytes is reported. The mother is phenotypically normal but shows the same unstable r(21). This is another case demonstrating that a chromosomal aberration does not necessarily lead to infertility by meiotic failure. Nevertheless, segregation of ring chromosomes is problematic for two reasons: mitotic problems of the ring structure itself and synaptic difficulties during the pachytene stage. PMID- 2253943 TI - A 45,X male with molecular evidence of a translocation of Y euchromatin onto chromosome 1. AB - A 45,X complement was found in lymphocyte and fibroblast cultures of a male infant with severe growth and mental retardation and mild dysmorphism. Lymphocyte DNA from this patient was found to contain Yp chromosome sequences. In situ hybridization (ISH) with the 50f2 probe led to a clear assignment of euchromatic material on the short arm of chromosome 1. This observation and others from the literature argue in favour of the conclusion that all 45,X males are probably either the result of undetected mosaicism or are carriers of Y translocated material. PMID- 2253945 TI - [IgA anti-endomysium antibodies in dermatitis herpetiformis: a sensitive marker of gluten enteropathy]. AB - The paper reports the results of a preliminary study using indirect immunofluorescent methods on serum samples from 20 patients affected by dermatitis herpetiformis in various phases of development and from 7 patients affected by celiac disease in order to document the presence of anti-endomysium IgA antibodies. Serum samples from 10 patients affected by bullous pemphigoid, 1 patients with linear IgA dermatitis and 10 patients with other bullous dermatosis were included as controls. Whereas the presence of these antibodies in varying titres, ranging from 1:10 to 1:80, was confirmed in all case of dermatitis herpetiformis, no antibody activity was observed in control patients. On the basis of these findings and of other published data, it is possible to conclude that these antibodies are directly correlated to intestinal damage, but there is no relationship with the clinical characteristics of skin symptoms or with junctional immunopathological evidence. PMID- 2253946 TI - A clinical contribution to guideline criteria in the excision of pigmentary lesions. AB - The clinical diagnosis of cutaneous melanoma is often difficult at the first stages of the malignant proliferation. The proposed anamnestic and clinical guidelines can offer useful criteria for the majority of the cases but sometimes a preventive excision is required for lesions that only partially fulfill the classic markers of "at risk" lesions. In this paper based on a comparative study between 2000 pigmented lesions and 40 melanomas of uncertain clinical diagnosis, the Authors recognize 5 statistically significant clinical pattern of benign pigmented lesions undistinguishable from clinically unusual melanomas. Epidemiological data about sex and age of the patients, histologically classification, site of the pigmented lesions and malignant transformation of congenital nevi are also reported. PMID- 2253947 TI - [Clinical framework of psoriatic arthropathy. Proposal of an evaluation protocol]. AB - Psoriatic arthropathy is an inflammatory seronegative arthritis characterized by an involvement of peripheral or axial joints in association with psoriasis. In this study the clinical features of both skin and joints have been observed simultaneously by a rheumatologist and a dermatologist. We have finally proposed a clinical protocol based on PASI to evaluate psoriasis and on a simple subset classification to estimate joint involvement. PMID- 2253948 TI - [HPV-induced subclinical lesions of the male genitalia. Use of a colposcope]. AB - Thirty-nine HIV-negative men, without apparent genital warts, were evaluated for evidence of subclinical genital condylomata by visual examination of the genitalia with colposcopy after the application of 5% acetic acid. 24 patients (group I) had a history of recurrent genital condylomata; 8 (group II) were sexual partners of women with HPV-related lesions and 7 (group III) presented another sexually transmitted disease. Under colposcopic magnification, acetowhite areas were biopsied for conventional histology and in situ hybridization using 6/11, 16/18 and 31/35/51 HPV-DNA probes. Colposcopy and histologic features were positive for condylomata acuminata in 16 patients of group III (14%). HPV 16/18 - whose oncogenic potentiality is well known - was detected in 3 patients: of these, one patient of group I presented a histologic picture suggestive of bowenoid papulosis. PMID- 2253949 TI - [Chronic urticaria and allergy to Acari. Experience with a specific desensitization therapy]. AB - Eighty-five patients affected by chronic urticaria (45 females and 40 males) were submitted to intradermal tests with house and storage mites in order to evaluate a possible sensitization to these allergens. The same allergological tests were performed in an 80-subject control group. The results showed immediate cutaneous reactivity to one or more mites in 40 patients (47%) while only 6 positivities (7.5%) were found in the control group. 27 patients, out of the 40 allergic to mites, were submitted to specific desensitizing therapy. 6 of them showed a complete recovery, 20 good results and only 1 slight improvement of clinical manifestations. These data allow us to hypothesize that the allergy to mite allergens is an important etiopathogenic factor in several chronic so called "idiopathic" urticarias. PMID- 2253950 TI - [A case of Fiessinger-Leroy-Reiter syndrome. Etiopathogenic, diagnostic and therapeutic problems]. AB - The Authors report the case of a young man with urethritis, conjunctivitis and oligoarticular arthritis. These symptoms are characteristic of Reiter's syndrome. Our patient also presented an inversion of CD4/CD8 ratio but the number and the activity of natural killer cells were normal and the research for HIV was negative. On the contrary the research for Chlamydiae by fluorescein-binding antibodies in urethral fluid was positive while the human leukocyte antigen HLA B27 was absent. The patient has been successfully treated by tetracycline and steroids. The Authors discuss the diagnostic, etiopathogenetic and therapeutical problems of this case, matching their findings to the up-to-date knowledge of Reiter's syndrome. PMID- 2253951 TI - [Iso and Kikuchi syndrome. Description of a case]. AB - A 2 1/2-year old Italian boy affected by Iso and Kikuchi syndrome is reported. The clinical examination showed hemi-onychogryphosis of both index fingers. Roentgenograms of the affected fingers showed bifurcation of the distal phalanges in the lateral view. PMID- 2253952 TI - [Tricholemmal hamartoma]. AB - A 23-year-old man with a keratotic-nodular lesion localized on the neck since infancy is reported. Histologically, there was a funnel-shaped follicle with central horny material and multiple digitations of the follicular sheath epithelium with some features resembling dilated pore of Winer. In addition, there were pale dyskeratotic epithelial cells in the infundibular portion of the tumor and in the surrounding epidermis. For this unusual tumor the term of tricholemmal hamartoma is proposed. PMID- 2253953 TI - [Cutaneous calcinosis with transepithelial elimination in porphyria cutanea tarda. Chemico-structural characterization]. AB - The Authors describe a case of porphyria cutanea tarda with subcutaneous calcinosis which sustains transepidermal elimination at certain points. The structural and chemical characterization of this material revealed a kind of apatite similar to that of depositions present in calcified human aorta wall and human mitral valve. PMID- 2253954 TI - [Cutaneous extramedullary hematopoiesis in idiopathic myelofibrosis. Description of a case]. AB - The Authors present a case of cutaneous extramedullary hematopoiesis in a 63-year old male patient with agnogenic myeloid metaplasia. The skin lesions appeared before splenectomy as multiple papules and nodules on the trunk. Histologic examination of a lesion showed all the tree components of the hematopoietic tissue, i.e. myeloid, erythroid and megakaryocytic series. A review of the literature revealed 18 previously reported cases, with polymorphous clinical manifestations of skin involvement. The possibility of extramedullary hematopoiesis should be considered in a patient with agnogenic myeloid metaplasia who shows cutaneous eruptions. PMID- 2253955 TI - [Erythematodes-like paraneoplastic syndrome. Description of a case]. AB - The Authors describe a case of a 65 year-old man with paraneoplasic syndrome, presenting erythematous-edematous figure lesions. Clinical, histological and immunological features were suggestive of lupus erythematosus. PMID- 2253956 TI - [Oral hairy leukoplakia]. AB - We report our experience of oral hairy leukoplakia in HIV seropositive patients. Etiopathogenesis and relationship between oral hairy leukoplakia and HIV infection are briefly discussed, as well as its prognostic value. PMID- 2253957 TI - ["Specific" skin lesions in chronic lymphatic leukemia]. AB - Infiltrated skin lesions, histologically characterized by a perivascular and periadnexal lympho-histiocytic infiltrate in the upper and deep dermis, are quite frequently observed in patients with B-cell chronic lymphocytic leukemia (C-CLL). The correct identification of the actual nature of these lesions, defined as specific on clinical and histologic grounds, is essential for a proper staging of the disease and, consequently, for the prognostic evaluation. In 6 patients with B-CLL, we performed an immunohistochemical study of specific skin lesions, with the aim of exactly defining the actual nature of infiltrating cells. Only in 2 of 6 cases immunophenotyping evidenced the neoplastic B-cell nature of skin infiltrating lymphoid cells; this finding was clearly correlated with the clinical evolution of the disease, rapidly fatal in both cases. The results of the present study indicate that the immunohistochemical analysis of skin lesions allows the proper staging of the disease, thus giving an important prognostic indication. PMID- 2253958 TI - [Necrobiosis lipoidica diabeticorum in children. Description of a case]. AB - A case of necrobiosis lipoidica diabeticorum (NLD) in a 12-year-old male patient is described. Diabetes mellitus (DM) was diagnosed at the age of 1.5 years. The onset of the first NLD lesion had been previously observed at the age of 7, on the back of the left foot. Three new lesions appeared at the age of 8, one on the left leg, the others on the thighs. At the age of 12, four infiltrated, reddish patches, with slight central atrophy were evident on his lower extremities. Histopathological features showed foci of collagen degeneration with sclerosis, surrounded by a chronic, mainly perivascular, granulomatous infiltrate, made up of lymphocytes and histiocytes. The patient is now 19-year old, with no eye or kidney failure, owing to a constant metabolic control of DM. A constant follow-up of the patient demonstrated a self-resolution of NLD plaques, with no evidence of further lesions. PMID- 2253959 TI - Allosensitization induced suppression of various murine tumors: role of non-H-2 antigens in antitumor immunity. AB - Presence of alloantigens on various murine tumors was tested by tumor rejection in allosensitized Swiss mice. The results indicated the presence of alloantigen on immunogenic tumors like chemically induced fibrosarcoma (FS), ascitic sarcoma 180 (S 180) and immunogenic variant of lymphosarcoma (LS-A) in Swiss mice, while these antigens could not be detected by this procedure on spontaneous lymphosarcoma (LS). Allosensitization with skin graft was found to offer quantitatively higher antitumor resistance than the allosensitization achieved by allogeneic lymphocytes. Antitumor effect was not seen when tumor cells were inoculated earlier than day 3 of grafting. Further, host immunosuppression with whole body irradiation up to day of 3 of skin grafting abrogated the antitumor effect. H-2 compatible and non-H-2 incompatible skin graft sensitization of host could offer resistance against both S 180 and LS-A. Further, tumor immune mice rejected H-2 compatible, non-H-2 incompatible skin graft significantly earlier. PMID- 2253960 TI - Effect of nutritional status on mutagenicity of urine excreted by rats treated with standard/experimental carcinogens. AB - Urine samples, collected from Sprague Dawley rats treated with extracts of tobacco/masheri, benzo (a) pyrene, N'-nitrosonornicotine, N'-nitrosodiethylamine and maintained on semi-synthetic diets sufficient or deficient in Vitamin A, B and protein were tested for mutagenicity using Salmonella/microsome assay. The mutagenic activity of urine or various treated groups was in the order deficient diet greater than standard laboratory diet greater than nutritionally sufficient diet. Present results confirmed the earlier observations that nutritionally deficient animals are likely to have more exposure to mutagenic metabolites that are generated by increased phase I enzymes and decreased detoxification system. PMID- 2253961 TI - Antifertility effects of leaf extracts of some plants in male rats. AB - Ethanolic leaf extracts of different local folklore plants (Azadirachta indica, Beaumontia grandiflora, Chordia dichotoma, Casiarea tomentosa, Diospyros embryopteris, Milletia auriculata and Melia azedarach) were investigated for antifertility effects on male rats in oral doses of 100 mg/kg daily for 21 days. Though, none of these extracts interfered with spermatogenesis, anti implantational and abortifacient effects were observed in females mated by the males fed with leaf extracts of A. indica and C. dichotoma. Leaf extract of B. grandiflora besides having anti-implantational and abortifacient effects, had luteolytic effects. Abolition of libido in 100% males by leaf extracts of D. embryopteris and M. azedarach and in 60% of males by extract of C. tomentosa preclude these plants for antifertility use. PMID- 2253962 TI - Effects of centchroman, a synthetic estrogen antagonist on the fertility of female hamsters. AB - Centchroman (3, 4-trans-2, 2-dimethyl-3-phenyl-4-p-beta-pyrrolidinoethoxy-phenyl 7-methoxy-chroman) , a non-steroidal, estrogen antagonist, injected subcutaneously (2 mg/kg body wt) on days 1, 2 and 3 post-coitum in hamsters, prevented implantation in 70% of the animals. A significant decrease in the circulating levels of estradiol and progesterone was observed on day 4 post coitum as compared to control animals following the treatment of centchroman. The activities of various lysosomal enzymes were also found diminished in the treated animals. This study shows that centchroman may act as an anti-implantation agent in hamsters indicating that estrogen plays a key role during the process of ovum implantation in this species. PMID- 2253963 TI - Effect of cyproheptadine on glucose tolerance, serum insulin and structure of pancreatic islets in rats. AB - The effect of cyproheptadine (CPH) on glucose tolerance, serum immunoreactive insulin (IRI) and structure of pancreatic islets in albino rats has been studied. Hyperglycemia with glucose intolerance was observed after 10 days of administration of CPH (40 mg/kg, ip). There was insignificant change of fasting IRI after the treatment. Histological studies indicated degranulation and vacuolation of beta cells with enlargement of capillaries. Improvement in blood glucose, glucose tolerance and structure of islets with proliferation of small pancreatic ducts and cell cords were observed 10 days after the withdrawal of CPH. PMID- 2253965 TI - Restoration of limb regeneration ability in frog tadpoles by electrical stimulation. AB - Electrical stimulation of advanced tadpoles of Rana breviceps for 24 hr with 3 microA current after hindlimb amputation through shank and ankle slightly increased the number of perfect regenerates as compared to controls. When amputation was made through thigh in tadpoles of the same stage regeneration failed in all cases of the controls but 24 hr stimulation of these tadpoles after similar operation with 3 and 10 microA currents induced fair degree of regeneration in 9 and 40% cases, respectively. PMID- 2253964 TI - Effect of gossypol on pituitary reproductive axis: ultrastructural and biochemical studies. AB - Oral administration of gossypol induced sterility in male rats by 10 weeks, at a dose of 15 mg/kg body weight/day. The pituitary FSH gonadotroph cells showed dilated endoplasmic reticulum and accumulation of secretory granules in the cytoplasm. LH cells were degranulated. The Leydig cells showed enhanced synthetic activity. There was no change in testis weight and testicular RNA, lipids and cholesterol in the treated group while significant increase was observed in DNA content. Testicular sialic acid content decreased significantly over controls. The Sertoli cells, spermatogonia, spermatocytes and early spermatids were not affected after the treatment. The weights of prostate, seminal vesicle were recorded normal and there were no ultrastructural variations. The levels of acid and alkaline phosphatase and RNA in prostatic tissue were insignificant as compared with controls. However, DNA content of prostate gland showed a significant increase. Sialic acid of seminal vesicle + coagulating gland were within the control range. A marked reduction in fructose values from the same organ was noted. PMID- 2253966 TI - Effects of zeitgeber shifts on gonadal function in male domestic fowls. AB - Effects of shifting light dark (LD) schedule of 8 hr/week on comb height and gonadal development were investigated in male domestic fowls. Three-day-old birds were exposed to repeated delay (westward shift) or repeated advancement (eastward shift) of the LD schedule at weekly intervals till they attained the age of 20 weeks. Control birds were held in fixed LD 12:12 hr light/dark schedule. Comb height was monitored at weekly intervals beginning at the age of 7 weeks. At 12th, 16th and 20th week 5 birds from each schedule were sacrificed and gonadal volume was recorded. Results indicate that comb and gonadal growth were significantly higher in advance-schedule birds when compared with control and delay-schedule birds. Histologically, testes of advance-schedule birds were more active when compared with those of control and delay-schedule birds. It appears that the eastward shifts of the synchronizer schedule may exert stimulatory influence on gonads. PMID- 2253967 TI - Distribution of mercury and evaluation of testicular steroidogenesis in mercuric chloride and methylmercury administered rats. AB - Intraperitoneal administration of methylmercury chloride (MMC) and mercuric chloride (MC) to male rats in doses of 5, 10 micrograms MMC/kg or 50, 100 micrograms MC/kg for 90 days induced cellular disintegration of Leydig cells which was conspicuous on day 30 and onwards in the exposed groups. Progressive degeneration of Leydig cells and decrease in their nuclear diameter and population were associated with gradual increase in deposition of mercury. Gradual diminution of 3 beta-hydroxy-delta 5-steroid dehydrogenase activity in Leydig cells after MMC or MC treatment was correlated with different structural deformations of the cells over 90 days. Moreover, a significant decrease in serum testosterone levels by day 90 confirmed steroidogenic impairment after MMC or MC treatment. PMID- 2253968 TI - Effect of steroidal fraction of seeds of Abrus precatorius Linn. on rat testis. AB - Dose-dependent degenerative changes in the testicular weights, sperm count, later stages of spermatogenesis and Leydig cells are observed in testis of rats treated with steroidal fraction of seeds of A. precatorius. These are correlated with the dose-dependent decrease in the enzyme activity of 3 alpha, 3 beta, 17 beta hydroxysteroid dehydrogenases, glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase and leucine aminopeptidase. The steroidal fraction may also exert its influence indirectly at the pituitary level by a feedback mechanism, leading to decrease in production and release of testosterone which results in significant alterations in the testis. PMID- 2253969 TI - Modification of radiation induced lipid peroxidation by calmodulin antagonists. AB - It has been shown that calmodulin antagonists provide radio-protection in euoxic and sensitization in hypoxic conditions. This differential protection in euoxic conditions might have arisen from the interaction of calmodulin antagonists with oxygen free radicals. This possibility has been tested in the present communication. Radiation induced lipid peroxidation process in liposomes has been used for this purpose. Liposomes prepared from L-alpha-lecithin were irradiated with or without calmodulin antagonists. Calmodulin antagonists inhibited lipid peroxidation significantly. The inhibition was found to increase with increase in concentration of the drugs. These observations suggest that calmodulin antagonists have a capacity to scavenge oxygen free radicals involved in initiation and/or propagation of lipid peroxidation process. This may be the reason for their differential radioprotection in euoxic conditions in biological systems. PMID- 2253970 TI - Microcalorimetric studies on cell survival and repair after UV induced damage. AB - Rate of heat production during cell proliferation following UV-irradiation of respiratory-deficient yeast cells was measured as a function of time (p-t curve) in a batch microcalorimeter. Following observations were made: (a) All growing cell cultures showed 3 distinct phases of heat production namely lag, exponential and declining phases of rate of heat production. (b) Duration of the lag phase is inversely proportional to the number of cells capable of proliferation. (c) After UV-irradiation, lag phase increased in a dose dependent manner. (d) Liquid holding reactivation increased the surviving fraction and reduced the lag phase in p-t curves. Presence of 2-deoxy-D-glucose during liquid-holding prevented the reduction in lag phase due to the inhibition of repair processes. PMID- 2253971 TI - Histomorphochemical effects of shortwave diathermy on healing of experimental muscular injury in dogs. AB - The biceps femoris muscle was surgically incised and sutured in 10 clinically healthy mongrel dogs, aged 1-2 yr and weighing 10-15 kg. The surgical wounds of 5 dogs were exposed to shortwave diathermy for 5 min daily for 7 days, starting a day after the creation of trauma. The remaining 5 dogs served as control. After 15 days of healing, the tissues from biceps femoris muscle were collected and subjected to histomorphological and histochemical examination. Mature collagen bundles were seen at healing site in diathermy treated animals while there were immature collagen fibres and more number of fibroblasts in control animals. Normal muscle fibres could be seen on either side of the healing tissue in treated animals whereas in control animals, atrophied and necrosed muscle fibres were encountered. The neutral and acid mucopolysaccharides, lipid droplets in the intermyofibrillar area and the activity of alkaline phosphatase, adenosine triphosphatase and lactate dehydrogenase at the healing site was better in treated as compared to controls. PMID- 2253972 TI - Maternal nutrition and development of intestinal functions: II--Effect of feeding high protein and high fat diets to lactating rats. AB - Effects of feeding high-protein (HP) and high-fat (HF) diets to lactating rats have been studied on the development of microvillus membrane enzymes and glycosylation in suckling rats. The activities of sucrase and lactase were significantly (P less than 0.01) decreased in the pups reared on HP fed dams. Alkaline phosphatase (AP), leucine aminopeptidase (LAP) and gamma-glutamyl transpeptidase (gamma-GTP) activities were essentially similar in HP and pair-fed groups. Pups reared on dams fed HF-diet, revealed nearly a 20% increase in disaccharidase levels and a significant (P less than 0.05) decrease in AP activity compared to the pair-fed controls. The activities of LAP and GTP were unaffected under these conditions. Sialic acid content was unaltered, however, fucose level of the membranes was significantly reduced in pups nursed by mothers fed HP-(P less than 0.05) or HF-(P less than 0.01) diet. The binding of 125I labelled wheat germ agglutinin and Ulex europeus agglutinin was in agreement to the data on sialic acid and fucose contents of the membranes. The binding of peanut agglutinin to microvillus membranes was enhanced by 31% and 21% in HP and HF groups, respectively. These findings suggest that the quality of maternal nutrition affects the enzymes and glycosylation of brush-borders in developing rat intestine. PMID- 2253973 TI - Concurrent analysis of plasma retinol and alpha-tocopherol by isocratic HPLC. AB - A simple, rapid and reliable method is described for simultaneous determination of plasma retinol and alpha-tocopherol. Plasma is deprotenized with 100% ethanol which contains retinyl acetate as internal standard and later extracted with HPLC grade n-hexane. The evaporated organic layer is reconstituted with methanol; diethyl ether (75:25 v/v) and injected onto a 250 x 4.6 mm column of zorbax CIS ODS C18 at a 1.5 ml/min flow rate. The system is monitored at 280 nm for both retinol and alpha-tocopherol. Intrabatch CVs were 3.9% for retinol and 1.8% for alpha-tocopherol respectively. Interbatch CVs over a 8-12 weeks period were about 9.48% for retinol and 6.7% for alpha-tocopherol. Our results agree well with those of retinol and alpha-tocopherol in quality control samples. This method should prove useful for routine analysis in clinical and epidemiological work. PMID- 2253974 TI - C-reactive protein (CRP) in haemolymph of a mollusc, Achatina fulica Bowdich. AB - C-reactive protein (CRP) was found to be one of the major components of the haemolymph of A. fulica with a normal level of approximately 2 mg CRP/ml haemolymph. Immunological cross-reactivity was found between CRP from A. fulica, a mollusc and Limulus polyphemus, an arthropod. The present finding demonstrates the evolutionary significance of C-reactive protein. PMID- 2253975 TI - Influence of pituitary on histology of Bidder's organ in castrated toad Bufo melanostictus. AB - Weight, number of follicles and corpora lutea of Bidder's organ increased significantly after castration of adult toad in breeding season. Removal of pituitary along with testes decreased both weight and number of follicles and corpora lutea. Administration of luteinizing hormone (LH) in castrated and hypophysectomized toad showed more or less similar result as that of control indicating that LH has an effect on the histology of Bidder's organ in the toad. PMID- 2253976 TI - Influence of parathyroidectomy on liver glycogen in rats treated with carbon tetrachloride. AB - Carbon tetrachloride (CCl4) brings about a rise in cytosolic free calcium which may lead to glycogen mobilization. Therefore, glycogen and glucose-6-phosphatase (G-6-pase) levels in the liver of parathyroidectomized (PTX) rats following CCl4 treatment have been estimated. CCl4 depletes both glycogen and G-6-pase levels in the liver. PTX followed by CCl4 administration, however, fails to restore liver glycogen and G-6-pase levels. The results suggest that neither cytosolic Ca2+ nor phospholipase A2 mediation is needed for glycogen mobilization, however, glucocorticoid intervention might have a role in such mechanisms. PMID- 2253977 TI - Avoidance learning under hypo and hyperglycemia in rats. AB - Learning behaviour under different glycaemic conditions were studied in albino rats using an avoidance box. When insulin and glucose levels were low after fasting, animals showed delay in avoidance learning. But there was no change in acquisition of learning after hypoglacaemia induced by insulin. This difference in behaviour under hypoglycaemia of almost similar severity is possibly due to difference in its rate of induction and activation of counter regulatory neuro endocrine mechanisms. Diabetic (alloxan) rats failed to improve learning. Besides, hyperglycemia, other factors like metabolic disturbances, cytotoxic effects of alloxan may have inhibited learning in this group. Hypo or hyperglycemia disturb the function of neuronal substrates responsible for learning and memory. PMID- 2253978 TI - Studies on non-steroidal anti-inflammatory and related biological activities of 5 (indan-1'-yl)tetrazoles and their intermediates. AB - Anti-inflammatory, analgesic and anti-pyretic activities of three new 5-(Indan-1' yl)tetrazoles and anti-inflammatory activity of corresponding carboxamides were compared to those of standard drugs, phenylbutazone and aspirin. The results indicated 5-(Indan-1'-yl)tetrazole as the most promising compound in chronic anti inflammatory and anti-pyretic tests. PMID- 2253979 TI - Significance of CA3 region of hippocampus in memory function. AB - In mobile unanaesthetised adult rabbits, spontaneous single unit activities of CA3 neurons of Hippocampus showed a specific change in firing pattern in response to conditioned stimuli (CS+). This pattern could be correlated with changes in the general behaviour of these animals. Major deafferntation of the CA3 region did not alter the conditioned response, though neuronal firing pattern and behavioural response changed to that of the pre-conditioned state after antidromic stimulation of CA3 region through fimbria. The importance of CA3 region in memory retention process has been indicated in these experiments. PMID- 2253980 TI - Nutritional status and spontaneous locomotor activity in the rat. AB - A considerable amount of energy may be saved by lowering the spontaneous locomotor activity when energy intakes are reduced. The results of the present study in rats undernourished for a period of 21 or 60 days and subsequently fed ad libitum diet did not show any differences in activity when compared to their respective control groups, either during the undernourished periods or well fed states. Although this would mean that the rats are not economising energy on activity, it is probable that these rats with lower body weights are contributing to energy saving mechanism by reducing the cost of activity per se since the cost of activity and body weight are directly related. PMID- 2253981 TI - Inhibition of positively rewarding behavior by the heightened aggressive state evoked either by pain-inducing stimulus or septal lesion. AB - Using a footshock elicited aggression paradigm, aggressive responses were scored in normal and in septal-lesioned adult male Wistar rats. Septal lesions were made electrolytically to include the medial and lateral septal nuclei. The lesion was confirmed by behavioral criteria (septal aggression) and post-mortem histology. The aggressive response types (threat, attack) of the septal animals were compared with their corresponding age and weight matched controls. Results showed a statistically significant increase (P = 0.05) in the number of attack responses but not the threat responses in septal animals. The modulatory role of the aggressive experience on responsiveness to positively rewarding or hedonic stimuli was assessed by quantifying the intracranial self-stimulation (SS) rates that were obtained before and after an aggression schedule. For testing the SS behavior bipolar electrodes were implanted in the ventral tegmental area- substantia nigra (VTA-SN). Results showed a decrease in SS pedal press rates in post-aggression schedule as compared to the pre-aggression period in the normal subjects. This depressing effect lasted for over a week. In septal lesioned rats the SS rates were virtually abolished even without having an aggressive schedule. These experiments revealed the effect of environment and of a brain area in provoking aggressive mood and its inhibitory consequence on responding for positive experience. PMID- 2253982 TI - Our experience with EMLA Cream (for painless venous cannulation in children). AB - The local analgesic efficacy of EMLA Cream (a eutectic mixture of lidocaine and prilocaine; Astra Pharmaceuticals, Sweden) in reducing the pain at Venous cannulation was investigated in a randommized blind study in 75 children scheduled for elective surgery. In 25 children placebo cream and in 50 children, EMLA cream was applied at the site of venous cannulation 1 hour prior. EMLA Cream was found to be highly effective (84% patients in contrast to 16% patients in placebo group; P less than 0.005). Local side effects of EMLA Cream were negligible. PMID- 2253983 TI - Effect of altered ventilations on human spinal and supra spinal reflexes. AB - The present study was aimed at evaluating the alterations in the human reflexes brought about by briefly altered ventilations. In 20 healthy young male volunteers, the H reflex and blink reflex were studied during normal ventilation, voluntary hypoventilation and voluntary hyperventilation. The latencies of these reflexes were compared. It was observed that the amount of altered ventilations used in the present study could not produce any significant change in these reflexes except in the case of the early response of the blink reflex. PMID- 2253984 TI - Program for drawing bar graphs on IBM Personal computers. AB - A simple program for drawing Bar graphs on IBM Personal computers is described here. This program is written in BASIC language and is user friendly. The program allows the operator to plot the bars with standard error, adjust the spacing between the bars and save the 'bar in a floppy disk. Legend can also be added at appropriate places in the graph. In the graphic mode, a hard copy can be obtained from a dot matrix printer using print screen command. PMID- 2253985 TI - A simple design of shock-scrambler unit for studies on foot-shock elicited aggression in rats. PMID- 2253986 TI - Biochemical evaluation of feeding Trichosanthes dioica seeds in normal and mild diabetic human subjects in relation to lipid profile. PMID- 2253987 TI - Indian contribution to reproductive physiology: the last 2 decades. AB - The end of twentieth century is witnessing far-reaching changes in the reproductive behaviour of modern man. Population is doubling now in a record time of 30 years in some parts of the world like India. On the other hand, living together without marriage and widespread use of contraceptives is making child bearing highly optional in the West. Technological advances in the realm of in vitro fertilization and genetic manipulation have opened up enormous possibilities, bringing us almost on the verge of Aldous Huxley's Brave New World. It is natural, therefore, that reproduction has become an attractive area of research for physiologists. We review here some of the significant contributions made by Indians to reproduction physiology during the last 20 years (1970-1990). Considerable pruning of available material has been necessary. The emphasis sometimes was on Physiologists although their contribution may not be exactly basic physiology, and sometimes on Physiology although the contributors were not exactly physiologists. PMID- 2253988 TI - Neuro immuno modulation by ventral hippocampus. AB - Bilateral electrical lesion at ventral hippocampal formation (VHF) did not affect some aspects of nonspecific immunity like total W.B.C. count, percentage of cells in differential count, their absolute count (lymphocyte and neutrophils) and neutrophil functions. The changes observed are due to non-specific craniocerebral trauma as the sham operated animals also showed a similar pattern of response. However the lesion at VHF increases the spleen cell count significantly whereas immunization in these animals decreases the spleen cell count. The thymus weight/body weight ratio also decreases in these animals. Our study confirms the neuroimmuno modulation and the influence of VHF on certain nonspecific immune parameters. PMID- 2253989 TI - Enteric infections and persistent diarrhea in developing countries. PMID- 2253990 TI - Child health and manpower: 2000 AD. PMID- 2253991 TI - Associated factors of protracted diarrhea. AB - The associated factors in 80 children (less than 2 yrs) with protracted diarrhea (greater than 21 days duration) and weight loss were: secondary carbohydrate intolerance (36): enteric pathogens (non typhoidal salmonella (11), enteropathogenic E. coli 'EPEC' (6), giardia (4), and shigella (3); cow's milk protein intolerance (3), gluten intolerance (3); miscellaneous (5); and undiagnosed enteropathy (9). Three of the EPEC showed localised pattern of adherence in vitro with HEP-2 cells. Most patients with salmonella and EPEC had severe secretory diarrhea with large fecal sodium losses. All 6 patients who died had secretory diarrhea and very high fecal sodium. All but 4 patients could be effectively managed with a chicken puree-glucose-coconut oil based diet. PMID- 2253992 TI - Mortality determinants and prediction of outcome in high risk newborns. AB - The aim of this study was to determine independent patient-related predictors of mortality in high risk newborns admitted at our centre. The study population comprised 100 consecutive newborns each, from the premature unit (PU) and sick baby care unit (SBCU), respectively. Thirteen high risk factors (variables) for each of the two units, were entered into a multivariate regression analysis. Variables with independent predictive value for poor outcome (i.e., death) in PU were, weight less than 1 kg, hyaline membrane disease, neurologic problems, and intravenous therapy. High risk factors in SBCU included, blood gas abnormality, bleeding phenomena, recurrent convulsions, apnea, and congenital anomalies. Identification of these factors guided us in defining priority areas for improvement in our system of neonatal care. Also, based on these variables a simple predictive score for outcome was constructed. The prediction equation and the score were cross-validated by applying them to a 'test-set' of 100 newborns each for PU and SBCU. Results showed a comparable sensitivity, specificity and error rate. PMID- 2253993 TI - Psychological adjustment of physically sick children: relationship with temperament. AB - The contribution of temperament and duration of illness in the variability in the psychological adjustment of children with chronic physical illness was studied. The temperament and psychological adjustment of a group of 50 children with chronic physical illnesses not involving the brain and a matched control group of 50 physically healthy children were assessed through Temperament Schedule and Childhood Psychopathology Measurement Schedule developed and standardized by the first author. Results indicated that sick children were less psychologically adjusted than the healthy controls and more adjusted than children referred for psychiatric concerns. Twice as many physically sick children (32%) showed maladjustment than did healthy children (16%). Temperament, particularly low distractibility, made a significant contribution to predicted variance (23%) in maladjustment whereas duration of illness did not. PMID- 2253994 TI - ELISA for diagnosis of tuberculosis. AB - Antigen A 60 of Mycobacterium bovis is a cell wall antigen with almost complete cross reactivity with antigen A 60 of Mycobacterium tuberculosis. This antigen was used for the ELISA technique for 100 cases suspected of childhood tuberculosis to evaluate the usefulness of the method in the diagnosis. The positivity rate in pulmonary tuberculosis was 65.1%, in central nervous system tuberculosis 50.0% and in the miscellaneous group 76.4%. The overall positivity was 61.0%, proving the utility of the method for diagnosis. PMID- 2253995 TI - Infant feeding practices in educated mothers from upper socio-economic status. AB - One hundred and twenty mothers from upper socio-economic status and education up to graduation level were assessed for infant feeding practices using a pre-tested questionnaire. Prelacteal feed of honey was administered by 51.7% and initiation of breast feeding delayed by more than 24 hours by 68.3% of mothers. Colostrum was discarded by 53% mothers; 83% introduced bottle feeding in the first month of life; and poor bottle hygiene was seen in 54% cases. Addition of semisolids was delayed by almost 50% of mothers, the reason given being fear of liver disorders. These observations highlight ignorance about basic infant feeding practices in the educated elite section of our country. Health education in schools, colleges, non formal gatherings and during the antenatal period are suggested as means to remove this ignorance. PMID- 2253996 TI - Maternal beliefs regarding diet during common childhood illnesses. AB - Maternal beliefs regarding diet during common childhood illnesses--diarrhea, fever, measles, cough and marasmus were determined in 143 rural mothers by using the interview technique. Some foods were preferred while others were restricted during episode of each illness, depending upon their 'hot' and 'cold', 'light' and 'heavy' and other characteristics, as determined by locally prevalent traditional dietary beliefs. 'Cold' foods like curd, butter milk were restricted during an episode of cough while 'hot' foods like tea, ginger with honey, were preferred. During diarrhea, 'light' foods like khichri, diluted milk and 'easy to digest' were preferred while 'heavy' foods like undiluted milk, roti and 'difficult to digest' were restricted. The study revealed that for a successful health education, it is important to identify local cultural practices and beliefs. The useful practices should be encouraged and reinforced while the harmful ones should be discouraged. PMID- 2253997 TI - Delayed cesarean section: neonatal outcome. AB - One hundred and twenty one consecutive cesarean sections producing single term, appropriate for gestational age neonates, out of which 85% were emergency cesareans, were included in this study. Fetal distress, nonprogress of labour, and cephalopelvic disproportion were major indications for surgery. The waiting period varied from less than 30 minutes to greater than 4 hours. More than 50% of neonates studied suffered from some problem. The morbidity increased significantly if cesarean section was delayed for more than two hours. PMID- 2253998 TI - Biomedical equipment: status and perspectives. National Symposium on "Equipment for Neonatal Use: a Need for Self-reliance.". PMID- 2253999 TI - Campomelic syndrome. PMID- 2254000 TI - Acute cerebellar ataxia: an unusual presentation of poliomyelitis. PMID- 2254001 TI - Diabetes insipidus and growth hormone deficiency following tubercular meningitis. PMID- 2254002 TI - Intramedullary dermoids in children. PMID- 2254003 TI - Combined factors V and VIII deficiency. PMID- 2254004 TI - Acute cerebellar ataxia in enteric fever. PMID- 2254005 TI - A newborn with hypertension. PMID- 2254006 TI - Iniencephalus apertus. PMID- 2254007 TI - Pacifiers--are they really necessary? PMID- 2254008 TI - Pneumothorax following rupture of a primary pulmonary hydatid cyst. PMID- 2254009 TI - Stress during postgraduate training in pediatrics. PMID- 2254010 TI - Upper and lower limb standards in newborns. PMID- 2254011 TI - Cerebral malaria--a diagnostic and therapeutic approach. PMID- 2254012 TI - Humoral antibody response and protective immunity in swine following immunization with the 104-kilodalton hemolysin of Actinobacillus pleuropneumoniae. AB - Five cesarean-derived, colostrum-deprived pigs were given three adjuvant supplemented subcutaneous and one intravenous injection of the purified 104-kDa hemolysin from serotype 1 Actinobacillus pleuropneumoniae CM-5. Six control animals received phosphate-buffered saline only. Five of six control pigs died within 24 h after challenge. The sixth control pig was moribund and euthanized after 48 h. All six pigs had pleuropneumonia, and A. pleuropneumoniae was isolated from all six lungs. None of the vaccinated pigs died as a result of challenge. After being euthanized, two pigs in this group had no lung lesions but three had chronic pleuropneumonia involving 10, 20, and 40% of the lung tissue. A. pleuropneumoniae was isolated from lung lesions of these three animals but not from the two pigs without lesions. The prechallenge hemolysin-neutralizing antibody titers in the vaccinated pigs were 1:10,900, 1:10,600, 1:4,800, 1:3,900, and 1:3,000, in order of increasing lung involvement. None of the control pigs had neutralizing antibodies. Enzyme-linked immunosorbent assay (ELISA) antibodies to capsule, lipopolysaccharide, and hemolysin were not detected in serum samples collected from the control pigs. In the vaccinated group, prechallenge sera did not contain ELISA antibodies to capsule or lipopolysaccharide. ELISA antibodies to the hemolysin were detected only in the prechallenge and postchallenge serum samples. These results indicate that pigs immunized with the 104-kDa hemolysin of serotype 1 A. pleuropneumoniae are protected against challenge with virulent bacteria. The association between neutralizing antibodies and protection indicates indirectly that the hemolysin is an important virulence factor. PMID- 2254013 TI - Purification and characterization of an outer membrane protein adhesin from Haemophilus parainfluenzae HP-28. AB - Outer membranes were isolated from Haemophilus parainfluenzae HP-28 by a mild extraction method followed by Sephadex G-150 gel filtration chromatography. The first peak (pool 1) recovered contained an activity which inhibited adherence of HP-28 cells to saliva-coated spheroidal hydroxyapatite. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of pool 1 revealed a dominant protein band of 34 kDa. The SDS-PAGE-purified 34-kDa protein was excised from the gel and used for antibody preparation in rabbits. The antiserum produced was analyzed by immunoblot and was shown to be monospecific for the 34-kDa protein. Anti-34-kDa protein antibody was purified from the rabbit antiserum by protein A Sepharose 6MB affinity chromatography. This antibody was then cross-linked to protein A-Sepharose 6MB to construct a second affinity column. The 34-kDa proteins were purified from outer membranes by this affinity chromatography. The 34-kDa protein was homogeneous, as confirmed by SDS-PAGE, isoelectric focusing, and reverse-phase chromatography analyses. Fab and Fc fragments of the purified anti-34-kDa protein antibodies were prepared by papain digestion, followed by carboxymethyl cellulose chromatography. Fab fragments from the anti-34-kDa protein antibody and the affinity-purified 34-kDa protein both showed significant inhibition of parent H. parainfluenzae HP-28 cell adherence to experimental salivary pellicle and to Streptococcus sanguis SA-1. PMID- 2254014 TI - Immune suppression induced by Actinobacillus actinomycetemcomitans: effects on immunoglobulin production by human B cells. AB - Actinobacillus actinomycetemcomitans produces an immunosuppressive factor (ISF) which has been shown to suppress mitogen- and antigen-induced DNA, RNA, and protein synthesis in human T lymphocytes. In this study, we examined purified A. actinomycetemcomitans ISF for its ability to alter immunoglobulin production by human B cells. The ISF caused a dose-dependent inhibition of pokeweed mitogen (PWM)-induced immunoglobulin G (IgG) and IgM production. Preexposure to ISF was not required to achieve maximal inhibition of immunoglobulin synthesis, as previously observed for its effect on T-cell activation. Nevertheless, the ISF appeared to act by irreversibly affecting the early stages of cell activation. While PWM-induced immunoglobulin production is under the influence of T regulatory circuits, it appears that the ISF interacts directly with B cells. First, ISF failed to alter either the synthesis of interleukin-2 (IL-2) or the expression of IL-2 receptors on T cells. Second, experiments in which individual purified populations of cells were exposed to ISF, washed, and placed back into tissue culture indicated that when all cells (i.e., T cells, B cells, and monocytes) were exposed to ISF, significant suppression was observed. However, when only one cell population was treated with ISF, suppression of both IgG and IgM synthesis was observed only when the B-cell-enriched population was exposed to ISF. These results in conjunction with our earlier findings suggest that the ISF functions via the activation of a regulatory subpopulation of B lymphocytes, which in turn either directly or indirectly (via suppressor T cells) downregulate both B- and T-cell responsiveness. Furthermore, it is hypothesized that patients who harbor A. actinomycetemcomitans could suffer from local or systemic immune suppression. This suppression may enhance the pathogenicity of A. actinomycetemcomitans itself or that of some other opportunistic organism. PMID- 2254015 TI - Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4. AB - We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G. PMID- 2254016 TI - Metalloproteases of infective Ancylostoma hookworm larvae and their possible functions in tissue invasion and ecdysis. AB - To infect their hosts, hookworm larvae must exsheath and migrate through connective tissue. A modified in vitro skin chamber was used to show that the human hookworm Ancylostoma duodenale and the zoonotic canine hookworm Ancylostoma caninum penetrate epidermis, basement membrane, and dermis in similar ways. These similarities in tissue invasion properties reflect the observed biochemical similarities in parasite protease composition. The larvae of both species contain protease activity that is inhibited by o-phenanthroline; this identifies the proteases as metalloproteases. The enzyme activities exhibit an alkaline pH optimum between pH 9 and 10. During modified sodium dodecyl sulfate polyacrylamide gel electrophoresis in which a protein substrate (either casein or gelatin) was used, the protease activities resolved into a major band at an Mr of 68,000 and a minor band at an Mr of 38,000. Proteases were released by living A. caninum larvae in vitro and degraded purified and radiolabeled casein to smaller peptides. Motile hookworm larvae were also incubated with purified and radiolabeled connective tissue macromolecules in vitro. Both Ancylostoma species degraded human fibronectin to a 60,000-Mr polypeptide intermediate, but could not degrade solubilized bovine elastin or human laminin. In contrast, the obligate skin-penetrating nematode Strongyloides stercoralis degraded all three substrates. This biochemical difference may explain some observed differences in invasiveness. PMID- 2254017 TI - Polymorphic expression of defensins in neutrophils from outbred rats. AB - We isolated and characterized a rat neutrophil defensin, RatNP-2, that differs from the previously described defensin RatNP-1 by containing Ser-7 in place of Arg-7. Although the resulting charge difference rendered RatNP-2 easily distinguishable from RatNP-1 on polyacrylamide gel electrophoresis gels, the two defensins exhibited very similar antimicrobial efficacies against Salmonella typhimurium, Staphylococcus aureus, and Candida albicans. The polymorphonuclear leukocytes of Sprague-Dawley rats obtained from one of two breeders also showed a marked polymorphism for defensin RatNP-4. This defensin was absent in two of seven animals and present in 1x or 2x relative amounts in the others. These observations indicate that a striking degree of defensin polymorphism exists in the polymorphonuclear leukocytes of outbred rodents. PMID- 2254018 TI - Schistosoma mansoni larvicidal activity of murine bronchoalveolar lavage cells. AB - We have investigated the ability of cells obtained from both normal and immune mice by bronchoalveolar lavage (BACs) to kill Schistosoma mansoni larvae in vitro. In cultures with mechanically derived schistosomules, high levels of larvicidal activity were displayed by BACs from both normal and irradiated cercaria-immunized C57BL/6 mice. Based on effector-to-target-cell ratios, BAC mediated killing was two- to threefold more efficient than killing mediated by macrophage-rich cell populations obtained from the peritoneal cavity. BACs from normal A/J mice were essentially as larvicidal as normal C57BL/6 cells. However, BACs from a strain of mouse (P/J) with a known macrophage defect possessed negligible larvicidal activity. Macrophages made up 85 to 95% of BACs from all three strains tested. In contrast to cells of the IC-21 macrophage cell line, B6 BACs did not show enhanced killing activity when preincubated with lymphokine containing supernatants. Lung schistosomules harvested 10 days after cercarial penetration were refractory to BAC-mediated killing. PMID- 2254019 TI - Tip-oriented adherence of Treponema denticola to fibronectin. AB - The adherence of Treponema denticola to ligands on cell surfaces or in basement membranes of periodontal tissues might play an important role in its pathogenicity. A direct microscopic assay was used to examine the binding of T. denticola to fibronectin and other protein substrates adsorbed on plastic cover slips. All strains of T. denticola that were tested adhered to fibronectin but to different degrees. The strains which bound in high numbers frequently bound by their tips. Type strain ATCC 33520 bound to fibronectin in high numbers (149 +/- 11.3 bacteria per microscopic field), with 60% bound by the tips. Strain e' bound in high numbers (140 +/- 10.2) and had the highest percentage of tip binding (98%); strain e bound in lowest numbers (39 +/- 8.2) and had the lowest percentage of tip binding (15%). Laminin supported binding at a level similar to that of fibronectin, as did fibronectin fragments which contained the cell binding domain peptides, RGDS. Type IV collagen and non-RGDS peptides did not support binding. Binding to fibronectin and laminin was inhibited by the addition of antifibronectin and antilaminin antibodies. By lowering the incubation temperature from 37 to 4 degrees C, the number of cells that attached decreased by 60% and tip binding was reduced by 50%. Pretreatment of the cells with collagen did not affect binding, whereas fibronectin pretreatment enhanced binding by 50% and laminin pretreatment resulted in a decrease of 60%. T. denticola adheres by its tips to fibronectin-coated surfaces, which suggests that fibronectin-specific adhesins cluster at the tips. PMID- 2254021 TI - Experimental infection of pig-tailed macaques (Macaca nemestrina) with Campylobacter cinaedi and Campylobacter fennelliae. AB - Campylobacter cinaedi and C. fennelliae have been associated with proctocolitis, bacteremia, and asymptomatic rectal infection, primarily in homosexual men. To more directly assess the pathogenic role of these organisms, we studied their disease-producing potential in 12- to 25-day-old pig-tailed macaques (Macaca nemestrina). Four infant monkeys were challenged with 10(8) to 10(9) C. cinaedi, three were challenged with C. fennelliae, two were challenged with C. jejuni, and one received no microorganisms. Watery or loose stools without associated fever or fecal leukocytes developed 3 to 7 days postinoculation in all of the animals given C. cinaedi, C. fennelliae, and C. jejuni, but not in the control animal. Stool cultures were simultaneously positive and remained so in the animals challenged with C. cinaedi or C. fennelliae for 3 weeks after inoculation despite the resolution of clinical illness. All of the animals challenged with C. cinaedi and C. fennelliae became bacteremic, and three had clinical evidence of septicemia. Histopathologic evaluation of rectal biopsies (five animals) and necropsy (one animal) showed no evidence of mucosal disruption. Specific immunoglobulin M and immunoglobulin G antibody responses occurred in all of the animals challenged with C. cinaedi and C. fennelliae, as determined by enzyme linked immunosorbent assay and immunoblotting. We conclude that C. cinaedi and C. fennelliae consistently produce a diarrheal illness accompanied by bacteremia and followed by prolonged gastrointestinal colonization in M. nemestrina. PMID- 2254020 TI - In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins. AB - Neutrophils play a major role in defending the periodontium against infection by oral, gram-negative, facultative bacteria, such as Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga spp. We examined the sensitivity of these bacteria to a mixture of low-molecular-weight peptides and highly purified individual defensin peptides (HNP-1, HNP-2, and HNP-3) isolated from human neutrophils. Whereas the Capnocytophaga spp. strains were killed significantly by the mixed human neutrophil peptides, the A. actinomycetemcomitans and E. corrodens strains were resistant. Killing was attributable to the defensins. The bactericidal activities of purified defensins HNP-1 and HNP-2 were equal, and both of these activities were greater than HNP-3 activity against strains of Capnocytophaga sputigena and Capnocytophaga gingivalis. The strain of Capnocytophaga ochracea was more sensitive to defensin mediated bactericidal activity than either C. sputigena or C. gingivalis was. The three human defensins were equipotent in killing C. ochracea. C. ochracea was killed under aerobic and anaerobic conditions and over a broad pH range. Killing was most effective under hypotonic conditions but also occurred at physiologic salt concentrations. We concluded that Capnocytophaga spp. are sensitive to oxygen-independent killing by human defensins. Additional studies will be required to identify other components that may equip human neutrophils to kill A. actinomycetemcomitans, E. corrodens, and other oral gram-negative bacteria. PMID- 2254022 TI - Iron-regulated outer membrane protein of Bacteroides fragilis involved in heme uptake. AB - Under iron starvation, Bacteroides fragilis expresses various iron-regulated outer membrane proteins. In this study, a deferrated minimal medium was used in growth experiments, and the role of one of these iron-regulated outer membrane proteins (a 44-kDa protein) in an iron uptake mechanism which acquires iron from heme compounds was elucidated. When a specific 44-kDa protein antiserum was used in a medium with heme as the only iron source, growth inhibition was observed. These results demonstrate that the 44-kDa outer membrane protein plays an important role in the uptake of heme in B. fragilis. PMID- 2254023 TI - Acute renal tubular necrosis and death of mice orally infected with Escherichia coli strains that produce Shiga-like toxin type II. AB - Escherichia coli O157:H7 strains have been implicated as etiologic agents in food borne outbreaks of hemorrhagic colitis and the hemolytic-uremic syndrome. A prototype E. coli O157:H7 strain, designated 933, produces Shiga-like toxin I (SLT-I) and SLT-II and harbors a 60-MDa plasmid. In a previous study, streptomycin-treated mice were fed 933 together with a derivative cured of the 60 MDa plasmid (designated 933cu). Strain 933cu colonized poorly, but in approximately one-third of the animals, an isolate of 933cu was obtained from the feces that had regained the ability to colonize well. This isolate, designated 933cu-rev, killed all of the animals when fed alone to mice. In this investigation, two types of experiments were done to assess whether SLT-I, SLT II, or both contributed to the death of mice fed 933cu-rev. (i) Mice were pretreated with monoclonal antibodies to SLT-I, SLT-II, SLT-I and SLT-II, or cholera toxin (as a control) before infection with 933cu-rev. (ii) Mice were fed either an E. coli K-12 strain carrying cloned SLT-I genes or the same K-12 strain carrying cloned SLT-II genes. The results of both types of experiments indicated that the deaths of the orally infected mice were due solely to SLT-II. Extensive histological and selected electron microscopic examinations of various tissues from the infected animals suggested that death was due to acute renal cortical tubular necrosis consistent with toxic renal damage. These data indicate a critical role for SLT-II, but not SLT-I, in renal damage associated with E. coli O157:H7 infection of streptomycin-treated mice. PMID- 2254024 TI - Production of tumor necrosis factors alpha and beta by human mononuclear leukocytes stimulated with mitogens, bacteria, and malarial parasites. AB - Tumor necrosis factors alpha and beta (TNF-alpha and TNF-beta) are multifaceted polypeptide cytokines which may mediate some of the significant changes in cellular homeostasis which accompany the invasion of the mammalian host by viruses, bacteria, and parasites. Although it is well established that bacterial lipopolysaccharide is a potent inducer of TNF-alpha, there is still very little known of the types of agents which can trigger the production of TNFs in mononuclear leukocytes. Using an enzyme-linked immunosorbent assay for measuring TNF-alpha and TNF-beta, we examined the capacity of various T-lymphocyte and beta lymphocyte mitogens as well as microbial components to stimulate production of these cytokines in culture. The mitogens phytohemagglutinin, concanavalin A, and pokeweed mitogen induced production of both TNF-alpha and TNF-beta, while whole killed Staphylococcus aureus and Bordetella pertussis, like lipopolysaccharide, were potent inducers of TNF-alpha but failed to stimulate TNF-beta production. TNF-alpha production was detectable within 1 h after stimulation, while TNF-beta production was not detected until after 8 h of culture. The bacterial products tetanus toxoid, purified protein derivative, pertussis filamentous hemagglutinin, and pertussis toxin were all able to induce TNF-alpha and TNF-beta production. Disrupted (frozen-thawed) Plasmodium falciparum-infected erythrocytes were also potent inducers of TNF-alpha and TNF-beta. The results demonstrated that a wide variety of microbial components are inducers of TNF-alpha. Some may not only be more effective than lipopolysaccharide but can also induce TNF-beta production. Furthermore, evidence is presented showing that TNF-beta but not TNF-alpha production correlates with lymphoproliferation. PMID- 2254025 TI - Functional activity of individual abscess neutrophils from mice. AB - In the absence of antibiotic therapy, viable bacteria can persist within intra abdominal abscesses in mice for at least 10 weeks. The mechanisms contributing to this survival are unknown, but abscess-derived neutrophils have impaired abilities to kill, in vitro, organisms engulfed in vivo. In order to determine whether subpopulations of abscess neutrophils might be discernible on the basis of phenotypic or functional criteria, cells from murine intra-abdominal abscesses were examined for phagocytic activity, CR3 expression, and H2O2 production in response to soluble and particulate stimuli. With respect to phagocytosis of Proteus mirabilis, abscess cells were no less efficient than peritoneal exudate neutrophils; no significant subpopulation of cells was incapable of phagocytosis in the presence of normal mouse serum. Using flow cytometry to examine abscess neutrophils for CR3 expression, we found that no subpopulations of cells were observed with unstimulated cells or with cells incubated with either phorbol 12 myristate 13-acetate or bacteria and serum. Intracellular H2O2 levels were measured by using the probe 2',7'-dichlorofluorescin diacetate. In general, incubation with phorbol 12-myristate 13-acetate resulted in similar increases in H2O2 production in all cells of the population. However, stimulation with bacteria and serum revealed a variable but consistent, poorly responsive subpopulation of neutrophils in abscess cell populations. Cell-sorting experiments showed that cells from the poorly responsive section of the FACS profile contained significantly higher numbers of abscess-derived bacteria, suggesting the presence of a subpopulation of viable abscess neutrophils harboring persisting viable bacteria. PMID- 2254026 TI - Hemin levels in culture medium of Porphyromonas (Bacteroides) gingivalis regulate both hemin binding and trypsinlike protease production. AB - Washed cells and Sarkosyl-insoluble outer membrane preparations of the black pigmented bacteroides Porphyromonas gingivalis W50 bound hemin. The amount of hemin removed from a buffered solution by both cells and outer membranes was significantly larger if bacteria had been grown in broths supplemented with 5 mg of hemin per liter rather than none. Conversely, cells grown without supplemental hemin bound relatively little. However, all preparations bound some hemin. In addition, hemin regulated the production of significantly higher levels of trypsinlike protease by P. gingivalis W50. The nonpigmented variant, W50 BE1, showed no such responses to the levels of hemin in the growth medium. PMID- 2254027 TI - Molecular analysis of hemolytic and phospholipase C activities of Pseudomonas cepacia. AB - By using a gene-specific fragment from the hemolytic phospholipase C (PLC) gene of Pseudomonas aeruginosa as a probe and data from Southern hybridizations under reduced stringency conditions, we cloned a 4.2-kb restriction fragment from a beta-hemolytic Pseudomonas cepacia strain which expressed hemolytic and PLC activities in Escherichia coli under the control of the lac promoter. It was found, by using a T7 phage promoter-directed expression system, that this DNA fragment carries at least two genes. One gene which shares significant DNA homology with both PLC genes from P. aeruginosa encodes a 72-kDa protein, while the other gene encodes a 22-kDa protein. When both genes on the 4.2-kb fragment were expressed from the T7 promoter in the same cell, hemolytic and PLC activities could be detected in the cell lysate. In contrast, when each individual gene was expressed in different cells or when lysates containing the translated products of each separate gene were mixed, neither hemolytic activity nor PLC activity could be detected. Clinical and environmental isolates of P. cepacia were examined for beta-hemolytic activity, PLC activity, sphingomyelinase activity, and reactivity in Southern hybridizations with a probe from P. cepacia which is specific for the larger gene which encodes the 72-kDa protein. There were considerable differences in the ability of the different strains to express hemolytic and PLC activities, and the results of Southern DNA-DNA hybridizations of the genomic DNAs of these strains revealed considerable differences in the probe-reactive fragments between high- and medium-stringency conditions as well as remarkable variation in size and number of probe-reactive fragments among different strains. Analysis of the genomic DNAs from hemolytic and nonhemolytic variants of an individual strain (PC-69) by agarose gel electrophoresis. Southern hybridization, and transverse alternating pulsed field gel electrophoresis suggests that the conversion of the hemolytic phenotype to the nonhemolytic phenotype is associated with either the loss of a large plasmid (greater than 200 kb) or a large deletion of the chromosome of P. cepacia PC-69. PMID- 2254028 TI - Haemophilus influenzae adheres to and enters cultured human epithelial cells. AB - Haemophilus influenzae is a common commensal organism of the human respiratory tract that initiates infection by colonizing the nasopharyngeal epithelium. In some individuals, colonization is followed by localized respiratory tract or systemic disease. To gain insight into the mechanisms by which H. influenzae attaches to and persists within the nasopharynx, we examined the interactions between a nonpiliated clinical isolate of H. influenzae and human epithelial cells. We noted substantial adherence that occurred independently of pili and required viable bacteria capable of de novo protein synthesis. Comparison of profiles of outer membrane proteins synthesized during incubation with epithelial cells for adherent and nonadherent bacteria identified several candidate adhesin molecules. In addition, a small number of adherent bacteria were capable of entering epithelial cells in a process that was inhibited by cytochalasin D and colchicine. The suggestion from our studies is that one or more of several newly synthesized nonpilus bacterial proteins are required for maximal in vitro adherence and invasion. We speculate that H. influenzae entry into epithelial cells may provide a mechanism for evasion of host defenses, thereby allowing persistence in the nasopharynx. PMID- 2254029 TI - Inhibition of heat-labile toxin from Bordetella parapertussis by fatty acids. AB - The ability of heat-labile toxin (HLT) from Bordetella parapertussis to induce skin lesions in guinea pigs was found to be inhibited by lipids isolated from skin layers of adult mice, which are refractory to the lesion-inducing activity of HLT. These lipids were identified as linoleic and oleic acids. Other long chain unsaturated fatty acids were also found to inhibit HLT; however, fatty alcohols, neutral lipids, phospholipids, cholesterol, prostaglandin, and leukotriene had no measurable effects on HLT action. The data presented in this report indicate that the ability of HLT to induce skin lesions in animals may depend, at least in part, on the free fatty acid content of the skin layer. PMID- 2254030 TI - Mechanism of pertussis toxin B oligomer-mediated protection against Bordetella pertussis respiratory infection. AB - Immunization with the B oligomer of pertussis toxin protected neonatal mice from a lethal respiratory challenge with Bordetella pertussis. All mice immunized with 8 micrograms of B oligomer survived aerosol challenge and had peripheral leukocyte counts and weight gains similar to those of mice immunized with pertussis toxoid before challenge and to those of control mice that were not challenged. Unprotected mice challenged with an aerosol of B. pertussis had an increase in peripheral leukocyte count, failed to gain weight, and died within 21 days of challenge. Protection appeared to be dose dependent, since a dose of 1 microgram of B oligomer per mouse prevented death in 100% of the mice challenged with B. pertussis, whereas 0.4 micrograms of B oligomer protected 50% of the challenged mice. Mice immunized with the B oligomer had increases in immunoglobulin G (IgG) anti-B oligomer in sera and in IgG and IgA anti-B oligomer in bronchoalveolar lavage fluids 1 to 3 weeks after respiratory challenge. Specific anti-B oligomer antibodies could not be detected in unimmunized, infected mice at the same time after challenge. Intravenous administration of the monoclonal antibody 170C4, which binds to the S3 subunit of the B oligomer, protected neonatal mice from B. pertussis respiratory challenge, while administration of an IgG1 anti-tetanus toxin monoclonal antibody, 18.1.7, was not protective. We conclude that anti-B-oligomer-mediated neutralization of pertussis toxin is one mechanism of protection in the mouse model of B. pertussis aerosol challenge. PMID- 2254031 TI - Identification of major Babesia divergens polypeptides that induce protection against homologous challenge in gerbils. AB - [35S]methionine-radiolabeled proteins from the Babesia divergens Rouen 1987 isolate were immunoprecipitated with immune sera from three potential hosts: human, ox, and gerbil. The results showed a constant humoral response against major babesial antigens. Similarly, immunoprecipitation of radiolabeled in vitro culture supernatant demonstrated that the exoantigens of 37, 46, 70, and 90 kDA were the immunodominant polypeptides, whatever the host. The effects of vaccination with concentrated supernatant from B. divergens Rouen 1987 in vitro cultures (30 to 40% parasitemia) were examined in gerbils inoculated with the homologous B. divergens isolate. Gerbils having received two or three injections of a whole vaccine dose (1.5 ml of parasitized culture supernatant equivalent [PCSE]) or of a 1:5 diluted vaccine dose (0.3 ml of PCSE) showed 100% survival after intraperitoneal challenge with 10(6) B. divergens-infected gerbil erythrocytes. Moreover, two or three injections of a 1:25 diluted vaccine dose (0.06 ml of PCSE) or 9% NaCl or 1.5 ml of unparasitized culture supernatant equivalent resulted in a mortality rate of 80 to 90% of the infected gerbils. Immunoprecipitation and immunofluorescence assays performed with antisera from vaccinated and control gerbils demonstrated that a single vaccine injection induced a humoral response, which increased slightly after the second or third injection. After challenge, antibody levels increased significantly, although the immunoprecipitation did not display any modification of Babesia antigen patterns. PMID- 2254032 TI - Platelet-interactive products of Streptococcus sanguis protoplasts. AB - To isolate a more native, platelet-interactive macromolecule (class II antigen) of Streptococcus sanguis, cultured protoplasts were used as a source. Protoplasts were optimally prepared from fresh washed cells by digestion with 80 U of mutanolysin per ml for 75 min at 37 degrees C while osmotically stabilized in 26% (wt/vol) raffinose. Osmotically stabilized forms were surrounded by a 9-nm bilaminar membrane, as shown by transmission electron microscopy. Protoplasts were cultured in chemically defined synthetic medium and osmotically stabilized by ammonium chloride. Spent culture media were harvested daily for 7 days. Each day, soluble proteins were isolated from media, preincubated with platelet-rich plasma, and tested for inhibition of platelet aggregation induced by S. sanguis cells. Products released from S. sanguis protoplasts and reactive with an anti class II antigen immunoaffinity matrix were able to inhibit S. sanguis-induced platelet aggregation. As resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, anti-class II-reactive protoplast products included silver stained bands of 67, 79, 115, 216, and 248 kDa. The 115-kDa protein fraction was isolated by gel filtration and ion-exchange chromatography. This form of the class II antigen contained N-formylmethionine at its amino terminus. Rhamnose constituted 18.2% of the total residual dry weight and nearly half of its carbohydrate content. Diester phosphorus constituted 1% of this fraction. After trypsinization of the protoplast products from either preparation, a 65-kDa protein fragment was recovered. This protoplast protein fragment and the S. sanguis cell-derived 65-kDa class II antigen, previously implicated in the induction of platelet aggregation, were shown to be functionally and immunologically identical. PMID- 2254034 TI - Molecular cloning and nucleotide sequence analysis of cholera toxin genes of the CtxA- Vibrio cholerae strain Texas Star-SR. AB - The ctx operons from the Vibrio cholerae El Tor strain 3083 and its CtxA- derivative Texas Star-SR were cloned, and their nucleotide sequences were compared. A single missense mutation in the Texas Star-SR ctxA cistron which results in the substitution of threonine for alanine at position 191 of the 258 amino-acid CtxA precursor was identified. Immunoblot analysis detected the mutant CtxA intracellularly early in the culture cycle but not extracellularly at any growth stage. PMID- 2254033 TI - An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin. AB - Tetanus toxin is composed of a heavy chain (100 kDa) and a light chain (50 kDa) held together by a single interchain disulfide bridge. An additional intrachain disulfide is present in the carboxy-terminal part of the heavy chain. Reduction of the two disulfide bonds in tetanus toxin with both chemical and proteinaceous reducing agents was studied. Dithiothreitol and 2-mercaptoethanol cleaved both the inter- and intrachain disulfide bridges of the toxin, while glutathione and cysteine were ineffective. Specific reduction of the single interchain disulfide link was achieved with the thioredoxin-thioredoxin reductase system, thus indicating that this bond is exposed at the protein surface. Also, dead or permeabilized cells were able to reduce the toxin. Such reduced toxin bound to neuronal membranes as well as the native toxin but was not neurotoxic. These findings open the possibility that reduction by cytoplasmic agents released by dead cells contributes to detoxification of tetanus toxin. Moreover, together with the notion that the light chain is the active form of the toxin in the cytoplasm, these results suggest that the interchain disulfide bond of tetanus toxin plays a role in nerve cell penetration. PMID- 2254035 TI - Susceptibility of inbred mice to Leishmania major infection: genetic analysis of macrophage activation and innate resistance to disease in individual progeny of P/J (susceptible) and C3H/HeN (resistant) mice. AB - We tested the possibility that two phenotypic traits, defective activation of macrophage antileishmanial activities and susceptibility to infection with Leishmania major, were controlled by the same gene. We used P/J (susceptible) and C3H/HeN (resistant) mice to breed F1, backcross (Bx), and F2 mice that were tested individually for both traits, each of which is known to be controlled by a single autosomal gene. We found no correlation between the macrophage defect and cutaneous disease. There was a correlation between development of systemic disease and defective macrophage activation in Bx mice; this correlation, however, was not confirmed in the F2 population. PMID- 2254036 TI - Effects of recombinant human interleukin-1 beta on accumulation of inflammatory peritoneal macrophages in mice treated with pertussis toxin. AB - In this study we report that treatment with recombinant human interleukin-1 beta (rIL-1 beta) (10 U per mouse, intraperitoneally) significantly increased the number of inflammatory macrophages in the peritoneal cavity of mice treated with pertussis toxin (PT) (1 micrograms per mouse, intravenously). The administration of rIL-1 beta in a single intraperitoneal dose (10 U per mouse) 1 or 2 days before challenge with PT did not prevent the decrease in the number of inflammatory macrophages in the peritoneal cavity of mice. On the other hand, the simultaneous administration of rIL-1 beta and PT, as well as the administration of rIL-1 beta 24 h after injection of PT, significantly counteracted the inhibitory effect of PT on inflammatory peritoneal macrophages. PMID- 2254037 TI - Genetic characterization and virulence of enterotoxigenic Escherichia coli mutants which have lost virulence genes in vivo. AB - Loss of K99 and STaP genes from enterotoxigenic Escherichia coli 431 during infection occurred by either plasmid curing or plasmid deletion. These mutants expressed the F41 adhesion and colonized neonatal pigs, but only those mutants that retained STaP caused diarrhea with significant weight loss. PMID- 2254039 TI - Endothelium-derived relaxing factor and vascular grafting. PMID- 2254038 TI - Purification and characterization of a protease produced by Vibrio mimicus. AB - A protease produced by Vibrio mimicus was purified to apparent homogeneity by ammonium sulfate fractionation and successive column chromatography on Sephacryl S-100 and Mono Q Monobeads. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) of the final preparation of the enzyme revealed the homogeneity of the purified enzyme. Conventional PAGE showed that the purified protease migrated as a single band with protease activity. The molecular weight of the protease was estimated to be about 31,000 on the basis of its mobility on sodium dodecyl sulfate-PAGE. The purified protease had both proteolytic and hemagglutination (HA) activities. The proteolytic and HA activities were inhibited by metalloprotease inhibitors and heat treatment. V. mimicus protease therefore appeared as a heat-labile, bifunctional molecule capable of mediating proteolysis and HA. The immunodiffusion analysis showed that the proteases produced by Vibrio cholerae and V. mimicus are immunologically cross-reactive. PMID- 2254040 TI - Heparin-like polymer surfaces: control of coagulation and complement activation by insoluble functionalized polymers. PMID- 2254041 TI - Activity of type 1 erythrocyte complement receptors in uremia and after renal transplantation. AB - The effect of uremia on the activity of the erythrocyte complement receptors type 1 (CR1), and the changes occurring after renal transplantation, were studied. The complement receptor activity was measured by immune adherence utilizing a rosette technique. Patients with terminal kidney failure on the hemodialysis program exhibited significantly lower values of the erythrocyte CR1 activity in comparison with healthy controls. The circulating immune complexes did not affect erythrocyte CR1 activity. After successful renal transplantation, irrespective of the immunosuppressive program used, a significant increase in erythrocyte CR1 activity appeared, similar to control group values. However, the activity of erythrocyte CR1, in the graft recipients under cyclosporin A treatment, was significantly higher than in the patients receiving azathioprine with prednisone. Therefore, it is possible that cyclosporin A, transported in the erythrocytes, modifies the complement receptor function. PMID- 2254042 TI - Comparison of two methods for the estimation of urea kinetics and introduction of a third simplified method. AB - It has been claimed that computed urea kinetic (UK) modelling in hemodialysed patients, for the estimation of protein intake, leads to an overestimation of protein catabolic rate (PCR). In the present study, three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 24 patients. The first method was the direct quantification method (DDQ) based on the collection of all urea eliminated from the body. The first computed method (ICMI) was the urea kinetic modelling method as described by Sargent. Dialyzer clearances were measured directly and not estimated by theoretical extrapolation. The second computed method (ICMII) is based on the indirect calculation of urea distribution volume (Vu), according to Watson, and of dialyzer clearances from this Vu and from pre- and post-dialysis urea concentrations. All three methods resulted in PCR's that were not significantly different (DDQ: 1.03 +/- 0.19; ICMI: 1.04 +/- 0.22; ICMII: 1.08 +/- 0.25 mg/Kg BW.24 hrs; p greater than 0.05). When the results were correlated, the following results were obtained: ICMI vs ICMII: r = 0.89, p less than 0.001; ICMI vs DDQ: r = 0.68, p less than 0.01; DDQ vs ICMII: r = 0.78, p less than 0.001. Intermutual comparison of Kt/V values resulted in virtually identical results, especially when comparing ICMI and ICMII, where the regression line equalled the identity line. In conclusion, all methods seem equally reliable in determining mean PCR and Kt/V. Our data, obtained with directly measured dialyzer urea clearances, do not confirm the earlier held opinion that computed modelling results in an overestimation of PCR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254043 TI - Raster-electron-microscopic investigations in large-bore catheters for extracorporeal detoxification. AB - Large bore catheters (n = 42, 31 patients) which remained in position for a period of between 2 to 73 days (mean = 26.8 days/patients) were investigated with raster electron-microscopy (scanning electron micrographic: SEM) and for bacterial colonisation. Microbiological findings indicated colonisation of the intravascular large bore catheters in 8 out of 42 catheters (19%). SEM morphological investigation showed bacterial colonisation in only 3 catheters (7%). The 3 different catheter materials had small deposits of fibrin and protein on the inner and outer surfaces after 2 days. This second layer covered the entire surface after 3 days and increased to a thickness of 3-60 microns in the following days. In this matrix erythrocytes, thrombocytes and granulocytes could also been seen. PMID- 2254044 TI - Cardiopulmonary dynamics during pumpless arteriovenous bypass for respiratory assistance. AB - The effect of a pumpless arteriovenous bypass with a microporous membrane oxygenator (MO) on the cardiopulmonary dynamics of dogs revealed an increase in cardiac output and cardiac work proportional to the increase in extracorporeal blood flow. Several current MOs offer so little resistance to blood flow that shunt flows exceeding a third of the normal cardiac output can easily be obtained. This should be enough for CO2 extraction covering metabolic production, and would add a non negligible amount of O2 to the blood. PMID- 2254045 TI - Effect of left ventricular assistance on sympathetic tone. AB - To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was detected in acute animal experiments. Our TH-7B pneumatically driven, sac-type ventricular assist device was used in 7 adult mongrel dogs. RSNA was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator circuit. The area of the integrated nerve discharge per unit time was calculated in the computer system and expressed as RSNA per unit time. During LVAD pumping, RSNA decreased with increase in blood pressure, with an increase in pulmonary artery flow, and with a decrease in left atrial pressure. These data suggest that LVAD has an effect on the sympathetic nervous system which is mediated by the aortic and cardiopulmonary baroreflex system. PMID- 2254046 TI - Long term cardiopulmonary bypass without systemic heparinization. AB - Cardiopulmonary bypass over 24-hours using heparin surface coated equipment, without systemic heparinization was analyzed in comparison to standard equipment with systemic heparinization in 8 open-chest canine experiments (37 +/- 7 kg). Mean duration of perfusion was 21 +/- 2 hours for the group perfused without versus 21 +/- 6 hours with systemic heparinization. The group without systemic heparinization could be perfused for 13 +/- 1 hours without transfusion of blood components whereas the pumpsucker was necessary during the whole procedure with systemic heparinization. Hematocrit dropped with systemic heparinization from 40 +/- 7% to 18 +/- 5% at 12 h versus a decrease from 38 +/- 4% to 15 +/- 1% without (with versus without: ns). Free plasma hemoglobin increased with systemic heparinization from 0.1 +/- 0.0 g/l to 1.4 +/- 1.2 g/l at 12 h compared with an increase 0.1 +/- 0.0 g/l to 0.3 +/- 0.1 g/l without (with versus without: p less than 0.05). Platelet levels dropped with systemic heparinization from 100 +/- 36% to 41 +/- 17% at twelve hours versus from 100 +/- 29% to 82 +/- 14 without (with versus without: p less than 0.05). Mean aortic pressure dropped with systemic heparinization from 73 +/- 12 mmHg to 53 +/- 4 mmHg at 22 hours whereas it remained at the same level without (83 +/- 6 mmHg). Improved hemostasis during long term open-chest cardiopulmonary bypass without systemic heparinization resulted in superior hemodynamics. PMID- 2254047 TI - Automatic modules for extracorporeal circulation control. AB - Maintenance of a constant level in the oxygenator during surgical extracorporeal circulation (ECC) is of paramount importance. We propose a device able to regulate the pump speed accordingly to the level in the oxygenator, and an automatic clamp to control venous return from the patient. The level regulator permits pump speed control and also stops the pump when a prefixed low level is reached (during ECC). Linearization of the level sensor has been made in order to optimize the PI regulator. Simulation results are presented and the regulator is evaluated in a clinical environment. The automatic clamp provides a good solution for reproducible and easy transitions in venous return. When coupled with the level regulator, the pump speed will increase automatically from zero to the correct equilibrium speed, with variable duration (from 30 seconds to 5 minutes) chosen by the operator. The same technique is used for stopping the ECC. These two devices are, in fact, modules, making up part of an evolutive device for ECC automation. The modules can exchange data with a supervising microcomputer. PMID- 2254048 TI - Biocompatibility of blood tubings. AB - We studied hemocompatibility of various blood tubings with C3a anaphylatoxin measurement and comparative electron scanning microscopy. The following tubing materials were tested: polyvinylchloride (PVC) plasticised with phthalate (PVC), pvc plasticised with phthalate coextruded with polyurethane (PIV), and two phthalate-free lines: pvc plasticised with trimellitate coextruded with polyurethane (TRI) and pvc plasticised with LT 360 (LTP). Results of C3a generation rate showed a significant activation by all blood tubings, with a reduced rate with PIV when compared to all others. Electron scanning microscopy showed marked alterations of PIV surface on tubings stored for 6 months. Protein deposits on internal surfaces after dialysis were similar whatever tubing material was tested, but adhesive cell number was greater with TRI when compared to PVC and LTP. Hemocompatibility is unchanged with phthalate-free tubings when compared to phthalate plasticised ones. In contrast with phthalate plasticised PVC there is no beneficial effect of polyurethane coextrusion with trimellitate plasticised PVC in regard to C3a generation. PMID- 2254049 TI - Combined dye adsorption and HPLC for determination of hydrophilicity in polymers. PMID- 2254050 TI - Long-term peritoneal clearances in patients on continuous ambulatory peritoneal dialysis. PMID- 2254051 TI - [Course and therapy of gastrointestinal motility disorders]. PMID- 2254052 TI - The cavernosal acetylcholine/papaverine response. A practical in vivo method for quantification of endothelium-dependent relaxation. Rationale and experimental validation. AB - An in vivo method has been developed for quantifying cavernosal endothelium dependent relaxation. The method is based on the fact that relaxation of the smooth muscle around the sinusoids of the penile corpora cavernosa activates the erectile veno-occlusive mechanism, and the degree of veno-occlusion can be precisely quantified by the pharmacologic maintenance erectile flow (PMEF) method. Pharmacologic maintenance erectile flows are determined after intracavernosal infusion of the endothelium-dependent relaxant acetylcholine (ACh) and the endothelium-independent relaxant papaverine, and expressed as an acetylcholine/papaverine ratio (APR). Control rabbits showed no changes from the test procedures themselves. In 12 test rabbits, control PMEFs after approximately 10(-7) mol ACh or papaverine averaged 0.7 and 0.5 ml/minute, respectively; APR averaged 1.3. Endothelial injury of the corpus cavernosum was produced by intracavernosal injection of 100 micrograms (16 x 10(-8) mol) of the detergent CHAPS or 1 ml of Renografin-76. Within 1 hour of injection of either agent, PMEF(ACh) increased markedly to approximately 6, PMEF(pap) increased minimally to approximately 0.9, and APR increased to about 7. These values gradually decreased to normal limits at six weeks. Endothelial injury and recovery were confirmed by electron microscopy. Thus, reduced cavernosal response to ACh relative to papaverine was indicative of endothelial injury. The ACh/papaverine response ratio offers promise as a practical and reliable in vivo method for quantifying endothelial-dependent relaxation. PMID- 2254053 TI - Effect of suction on specimen size in fine-needle aspiration biopsy. AB - High incidences of unsatisfactory specimens in fine-needle aspiration biopsy for cytology have been reported previously. Inappropriate aspiration techniques may account partly for this. In this study, the effect of suction on specimen size was studied in vitro using an automatic sampler. Bovine liver, testis, and pig's kidney were used as target tissues and biopsies were performed with 18-, 20- and 22-gauge needles. Specimen weight increased rapidly and linearly with suction force (P less than .001), regardless of the target tissue or needle diameter, when standard needle movement was applied. In the absence of needle movement, the suction force, rate of increase of suction, and duration of suction had no effect on the weight of the specimens. Needle movement alone, without suction, also produced meager specimens. Suction alone does not seem to tear fragments off target tissues. Nevertheless, in combination with needle movement, suction force plays an important role in the determination of specimen size. PMID- 2254054 TI - Quantitation of the in vivo kidney volume with cine computed tomography. AB - The authors examined the utility of cine computerized tomography (CT) for noninvasive determination of whole kidney, cortical, and medullary volumes. The right kidneys of 14 anesthetized dogs were scanned after an intravenous bolus injection of iohexol, and their volumes determined after boundary identification. After the scans, the kidneys were excised at postmortem examination and their volumes determined by fluid displacement. The mean (+/- standard error of the mean [SEM]) postmortem and in vivo renal volumes were 66.1 +/- 2.2 cc and 78.2 +/ 2.4 cc, respectively (r = 0.86; P less than 0.001). The difference was consistent with the blood, filtrate, and urine contents of the in vivo kidney. The in vivo cortical and medullary volumes correlated poorly with their postmortem volumes because of difficulties in boundary definition. These results demonstrate the feasibility for fast and reliable in vivo whole kidney volume quantitation by cine CT. PMID- 2254055 TI - Gadopentetate dimeglumine clearance in renal insufficiency in rabbits. AB - The total body clearance of gadopentetate dimeglumine (Gd-DTPA) was evaluated in 17 normal rabbits and 11 rabbits with renal insufficiency induced by angioinfarction. Serial measurements of the serum spin lattice relaxation rate (1/T1) were compared with actual gadolinium concentrations as determined by mass spectroscopy. Gadopentetate dimeglumine concentrations measured by both mass spectroscopy and magnetic resonance (MR) relaxometry decreased by two logs in both normals and rabbits with renal impairment by 24 hours and were highly correlated with each other (r = .98). The estimated total body clearance of gadopentetate dimeglumine was 14.1 +/- 0.56 cc/minute for the normal animals and 3.78 +/- 0.19 cc/minute for the impaired rabbits. These results indicate that gadopentetate dimeglumine is excreted rapidly, usually within 24 hours, even in the presence of renal insufficiency. PMID- 2254056 TI - Production and characterization of improved liposomes containing radiographic contrast media. AB - The authors have investigated liposomes prepared by the reverse-phase evaporation method (REVs) and a modification of this technique that employs a microemulsifier (MREVs), for the delivery of radiographic contrast media (RCM) to the liver and spleen. The modification entailed substituting a Microfluidizer (Microfluidics Inc., Newton, MA) for the sonication step of the REV technique. The MREV procedure is amenable to large-scale production and continuous-flow operation and yields products with high RCM encapsulation. Efficiently entrapped are ionic, high-osmolar diatrizoate (24.38 +/- 2.62% versus 8.35 +/- 0.55%; MREV versus REV), and nonionic, low osmolar Iotrolan (Schering AG, Berlin, FRG) (24.84 +/- 2.13% versus 7.25 +/- 1.19%) RCM with iodine-to-lipid ratio of 1.5:1. The MREV procedure, therefore, has practical advantages over the REV method. High liver and spleen uptakes of Iotrolan-containing vesicles were noted in normal rats. The diatrizoate MREVs lost their contents on contact with serum, resulting in urinary excretion of this agent. Computed tomography values of splenic and hepatic sections, 1 hour after intravenous injection of Iotrolan MREV (500 mgI/kg), are 0.78, and 0.08 Hounsfield Units (HU)/mgI/kg, respectively (versus 0.01, and 0.006 HU/mgI/kg for free Iotrolan). PMID- 2254057 TI - Magnetic resonance imaging of knee menisci. Comparison of spin echo pulse sequences. AB - Magnetic resonance imaging (MRI) is accurate in evaluating meniscal tears using spin echo pulse sequences. The purpose of this study was to systematically compare T1-weighted pulse sequences to two echo proton density/T2 (2eT2)-weighted sequences. Menisci were separated into four grades based on signal characteristics. In addition, all menisci were graded as positive or negative for tear. Twenty-three patients (46 menisci) were studied with both pulse sequences and the results were compared with arthroscopic findings. Using T1 sequences, 14 of 18 torn menisci and 26 of 28 untorn menisci were identified. Using 2eT2 sequences, 13 of 18 torn menisci and 26 of 28 untorn menisci were correctly identified. There was high correlation between T1 and 2eT2 sequences for torn versus untorn menisci and for grade of injury (P = .99). There is very little difference between T1- and 2eT2-weighted pulse sequences in evaluation of meniscal tears. PMID- 2254058 TI - Effects of cell membrane disruption on the relaxation rates of blood and clot with various methemoglobin concentrations. AB - The magnetic resonance imaging (MRI) characteristics of hemorrhage and clotted blood change with age. The effects of methemoglobin and cell membrane lysis, factors which in part may underlie this evolution of imaging characteristics, were studied using clotted and heparinized dog blood at various methemoglobin concentrations. Cell lysis did not alter the longitudinal relaxation rate (1/T1) in clotted or unclotted samples. Membrane lysis altered significantly the transverse relaxation rate (1/T2) in both clotted and unclotted samples. Lysed samples of oxygenated blood at 0% methemoglobin had significantly higher T2 values than intact samples. At 0% methemoglobin, clotted samples had slightly but significantly shorter relaxation times than unclotted samples. Within the samples studied, large changes in the state of oxygenation and methemoglobin content were observed in less than 24 h. Such changes necessitate frequent monitoring of these parameters if serial studies are to be done. PMID- 2254059 TI - Radiology in the French health-care system. PMID- 2254060 TI - Performance and consultation patterns in pulmonary radiology. PMID- 2254061 TI - Evaluation of iopamidol and diatrizoate in excretory urography: a double-blind clinical study. PMID- 2254062 TI - Standardization of the curriculum for resident education in diagnostic radiology. PMID- 2254063 TI - A joint course in emergency radiology for residents in radiology and in emergency medicine. AB - A basic course in emergency radiology has been developed and taught jointly to first- and second-year radiology residents and emergency medicine residents at the Medical College of Georgia. The course, comprising thirty-five lectures, was presented in a 5-month block. Both written and practical examinations were administered at the end of the course, and the course was evaluated by the participating residents. There was little overlap in examination scores between emergency medicine and radiology residents, with radiology residents scoring higher than emergency medicine residents. There was a wider gap in scores between the two groups on the practical than on the written examination. All participants considered the course useful and the material presented to be immediately applicable. PMID- 2254064 TI - Radiology of thoracic trauma. PMID- 2254065 TI - Octogenarian with vaginal bleeding and uterine mass. PMID- 2254067 TI - What's new in ophthalmology? PMID- 2254066 TI - Paget's disease with headache and disorientation. PMID- 2254068 TI - Topical philately--a severe case. PMID- 2254069 TI - Educational and socio-economic goals. PMID- 2254070 TI - Diabetic retinopathy. AB - Macular edema can occur early, especially in maturity onset diabetics. These patients will usually have blurred vision. An examination (through dilated pupil) will reveal fuzziness or hard exudates in the central retina. The ETDRS proved focal laser treatment to leaking blood vessels reduces vision loss. Proliferative retinopathy occurs after 12-15 years or more of diabetes in juvenile diabetics and any time in maturity onset diabetics. Proliferative disease may be completely asymptomatic until there is a vitreous hemorrhage or retinal detachment. The DRS showed scatter laser treatment reduces severe visual loss by at least 50% in patients with proliferative disease. If proliferative disease is not treated, it almost always causes blindness. We must shout this message to all primary care physicians and diabetics. If we are successful, we can eliminate preventable blindness in Iowa's diabetics. PMID- 2254072 TI - Watching your back: facts about IRS audits. PMID- 2254071 TI - Physicians and assisted suicide. PMID- 2254073 TI - Sight saving projects. PMID- 2254074 TI - Diagnostic and prognostic value of oral dipyridamole test using echocardiography. AB - The diagnostic and prognostic value of the oral dipyridamole test using echocardiography was evaluated in 47 consecutive patients undergoing coronary arteriography. The results of the tests were not communicated to the physicians treating the subjects during a 1-year follow-up. The test had a sensitivity of 54% and a specificity of 100% for predicting severe (greater than or equal to 70% luminal stenosis) coronary artery disease. Neither ST-T segment changes nor chest pain during the test were associated with the presence of severe coronary artery disease. In the subgroup of 34 patients with severe coronary artery disease, the appearance of left ventricular segmental systolic dysfunction or ST-T segment depression (greater than or equal to 1 mm) during the test has a strong predictive value for subsequent cardiac events during a 1-year follow-up. PMID- 2254075 TI - Spurious hypoglycemia, hyperkalemia and hypoxemia in chronic hemolytic anemia. AB - Spurious hypoglycemia and hyperkalemia were found in a patient with chronic hemolytic anemia due to an unidentified hemoglobinopathy. The patient had massive reticulocytosis, and many nucleated red blood cells were present in his blood smear. Hypoxemia was induced in vitro. No correlation was found between in vitro hypoglycemia and hyperkalemia. Reticulocytosis and the presence of nucleated red blood cells, as occurs in hemolytic anemia, should be added to the list of hematological causes of spurious hypoglycemia, hyperkalemia and hypoxemia. PMID- 2254076 TI - Neonatal low-dose gamma irradiation-induced impaired fertility in mature rats. AB - The reproductive capacity of mature rats at the age of 8 days was studied following neonatal exposure to 0.06 Gy dose of gamma-radiation. Decreased litter size and reduced body weight of the pups on weaning day, but not at parturition, were observed in female rats. The reduced litter size was not associated with impaired ovulation, impaired uterine implantation or mortality in utero, but resulted from increased death rate or at near parturition. Of the neonatally irradiated males 29% were found to be sterile and had degenerated or necrotic testes. The testicular damage and the reduced growth rate of the offspring of the irradiated females demonstrate the extreme sensitivity of the immature reproductive system to ionizing radiation, even at very low doses. PMID- 2254077 TI - Pattern of drug abuse and prevalence of antibodies to human immunodeficiency virus in heroin addicts in Jerusalem, 1989. AB - Intravenous drug abuse is a principal factor in the spread of AIDS. In contrast to many countries in the Western world, most of the heroin addicts in Israel do not inject. This study attempts to clarify the link between the pattern of drug abuse and seroprevalence for human immunodeficiency virus (HIV) among volunteers attending a detoxification clinic in Jerusalem. Three hundred heroin abusers were interviewed about their drug habits and sexual preference. In addition, all participants underwent HIV serological testing. The majority of them took heroin by smoking, with only 19% injecting the drug. None of the participants in the study were HIV seropositive. An association is seen between the pattern of illicit drug use in Israel and the low incidence of AIDS in this country. PMID- 2254078 TI - Occupational stress and well-being: do seafarers harbor more health problems than people on the shore? AB - The popular image of life at sea is one of stress: often difficult physical conditions, dislocation, isolation and less than ideal personal habits. In order to determine whether this stressful way of life is manifested when seamen's health status is assessed by standard measurements, we studied 144 sea captains and marine chief engineers as compared with a group of ordinarily employed men. The referent men were matched for age, ethnic origin, and level of education with the seamen. Outcome measures included a wide spectrum of physiological, psychological and behavioral indices. The comparisons revealed only mild differences between the two groups. Captains and chief engineers tend to harbor slightly higher levels of certain biochemical or physiological parameters (risk factors), such as serum cholesterol and uric acid, hemoglobin level and leukocyte count. Certain behavioral risk factors were more dominant among the seamen than among the control group (smoking level, alcohol consumption and lack of leisure time physical activity). The study group did not exhibit a greater prevalence of overt disease or a higher degree of psychological symptoms. It is suggested that the group under study represents a self-selected group of persons well adjusted to their job and their special way of life. PMID- 2254079 TI - Cerebrospinal fluid leak in the neonate--complication of fetal scalp electrode monitoring. Case report and review of the literature. PMID- 2254080 TI - Prevalence of helminths in dogs in the Hadera district of Israel. PMID- 2254081 TI - Glycated proteins and gestational diabetes mellitus. AB - The use of assays of glycated serum proteins (glycohemoglobin and fructosamine) as markers of glucose homeostasis is becoming a common modality in the evaluation of the pregnant diabetic patient. The purpose of this review is to provide basic information on the interactions between glucose and the protein molecules that lead to the formations of this complex, and to evaluate these tests for their efficacy in the screening and diagnosis of gestational diabetes mellitus, the identification of fetal congenital anomalies and in their relation to early fetal wastage, fetal macrosomia and neonatal complications. PMID- 2254082 TI - Typhoid vaccine--a double-edged sword? PMID- 2254083 TI - Measuring the effectiveness of medical interventions: new expectations of health services research. PMID- 2254084 TI - Patient Outcomes Research Teams and the Agency for Health Care Policy and Research. PMID- 2254085 TI - Consequences of variation in treatment for acute myocardial infarction. PMID- 2254086 TI - Assessing and improving outcomes: total knee replacement. PMID- 2254087 TI - Variations in cataract management: patient and economic outcomes. PMID- 2254088 TI - Health services research in a quick and dirty world: the New York City hospital occupancy crisis. AB - In 1987/1988, New York City experienced an unexpected health care crisis: a severe and prolonged communitywide shortage of inpatient hospital beds. A rapid rise in hospital occupancy rates dramatically ended a long-term decline in hospital utilization and left health care providers and policymakers baffled about both cause and remedy. This article describes the course of a short-term, intensive, midcrisis study that unraveled the reasons for the high occupancy rates. As a case study for a research effort that successfully yielded valid and timely results, this article illuminates the research design and methodological decisions that lay behind the findings and discusses the implications of those decisions. Key to the success of the study were a mandate to diagnose the crisis, a statewide patient discharge data base, our previous hands-on experience with that data base, active support for the study from the community of health care providers, and strong results. PMID- 2254089 TI - Changing practice patterns in the management of primary breast cancer: Consensus Development Program. AB - In the last decade, new knowledge has emerged concerning the efficacy of treatment for breast cancer. For that reason, the National Institutes of Health devoted a consensus conference to this topic. To determine whether the consensus conference had influenced practice patterns, and to evaluate the level of quality of care given to women with breast cancer, the medical records of 573 patients treated in ten hospitals throughout the state of Washington were abstracted and analyzed. Results showed no changes with respect to the consensus conference's recommendations for use of a total mastectomy with axillary dissection or the use of a two-step procedure in which the biopsy is performed first and therapeutic options are discussed before a definitive surgery is undertaken. Analyses of quality of care issues not addressed by the consensus conference revealed that 4 percent of the sample were explicitly staged preoperatively and 29 percent postoperatively and that little changed over time in the use of sentinel laboratory tests. These results also show that consensus recommendations will not necessarily change physicians' behavior even where change is possible, and that quality of care in diagnosis and treatment of breast cancer still needs to be addressed. PMID- 2254090 TI - Imaging prostate derived tumors with PET and N-(3-[18F]fluoropropyl)putrescine. AB - Because of the high uptake of polyamines by the prostate and by prostate derived tumors, polyamines have been considered as potential imaging agents for metastatic prostate cancer. We now report the successful PET imaging of the Dunning R3327H prostatic carcinoma with N-(3-[18F]fluoropropyl)putrescine (FPP), a positron-labeled putrescine analog. Additionally, the biodistribution of FPP in tumor bearing Copenhagen male rats is analyzed. The tumor uptake of FPP was high, and the tumor-to-muscle ratios at 1, 2, 3 and 4.5 h post-injection were 7.2 +/- 1.0, 5.61 +/- 1.65, 4.62 +/- 0.21 and 3.51 +/- 0.91 respectively. The estimated radiation dose for FPP was calculated from rat biodistribution data. The radiation dose estimates suggest that the critical organ, following the administration of FPP, is the upper large intenstine which receives 0.3 rad/mCi administered. PMID- 2254091 TI - Dynamic bone imaging in the differential diagnosis of skeletal lesions. AB - Dynamic bone imaging differs from routine multiphase bone scintigraphy by the use of time-activity curves (TACs) and quantitation of data. TACs were divided into an arterial plus blood pool phase (first 60 s at 1 frame/s) and a subsequent early bone uptake phase (24 min at 1 frame/min). Ratios of normalized integrals, from analogous regions were calculated to determine whether blood flow was abnormal. A key feature of the technique is the monitoring of the flow proximally and distally to the area of involvement. This was of importance in distinguishing between two diseases producing the same degree of local hyperemia. Dynamic bone imaging was applied to the differential diagnosis of arthritis, septic arthritis, cellulitis, osteomyelitis, tumor, avascular necrosis, Charcot joint, Legg-Perthes (LP) disease, and Osteochondritis Dissecans (OCD). Although the method is straightforward, there are technical and clinical factors that may affect interpretation of data. Asymmetries in flow may arise due to injection technique, interfering activity of bladder and/or bowel, vascular abnormalities, AV malformation, and venous backflow. The dynamic study is also sensitive to the effects of various modes of therapy. Consideration must be given to these technical and clinical factors for the avoidance of pitfalls in interpretation of the dynamic study. PMID- 2254092 TI - Preparation and evaluation of 99mTc-t-butylisonitrile (99mTc-TBI) for myocardial imaging: a kit for hospital radiopharmacy. AB - A previous method was modified to obtain [99mTc(TBI)6]+ by reacting Zn(TBI)2Br2 directly with 99mTcO4- in the presence of Sn2+ ions. [Cu(TBI)4]Cl was next used as a source of TBI. On reaction with 99mTcO4- and Sn2+ ions for 3 min at 100 degrees C, [99mTc(TBI)6]+ product of radiochemical purity greater than 90% and yield greater than 70% was obtained. Data of biodistribution in rats (2-2.5% in heart) and biokinetics in rabbits were satisfactory. The kit formulation was found to be stable and also safe for administration. PMID- 2254093 TI - Distributions of perfusion and lung water. AB - We investigated the feasibility of using 123I-iodoantipyrine (123I-IAP) and 99mTc labeled macroaggregated albumin (99mTc-MAA) to describe and compare the distributions of perfusion and water content in lung injuries. These radiopharmaceuticals were administered to 9 rabbits, 5 control and 4 with lung injuries. Isolated lungs were imaged by a scintillation gamma camera. The distribution of 123I-IAP outlined the entire lung mass whereas perfusion defect in the distribution of 99mTc-MAA was seen clearly in the case of severe lung injury. PMID- 2254094 TI - Infarcted heart uptake and biodistribution of radiolabelled anti-myosin monoclonal antibody in rat and dog myocardial infarct models. AB - A new mouse monoclonal antibody that recognizes alpha- and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin was obtained. The 125I- and 111In-labelled antibody, and its F(ab')2 and Fab fragments localize in isoproterenol induced infarcted rat heart, with the F(ab')2 fragment showing the highest uptake. Comparison with 99Tc pyrophosphate uptake in infarcted dog heart, induced by selective obstruction of a coronary artery, suggest that the 111In-labelled F(ab')2 localizes specifically in infarcted myocardium only. PMID- 2254095 TI - Antibody accumulation in small tissue samples: assessment by quantitative autoradiography. AB - Uptake of radiolabeled 125I monoclonal antibodies in small metastases can only be characterized by autoradiographic techniques. To obtain quantitative data out of autoradiographic images, a transformation of the essentially two-dimensional signal into the Bq per unit volume information is needed. Part of the calibration problem could be solved by using tissue-equivalent standard preparations. However, when aiming at a quantification of radioactivity in small areas (less than or equal to 2 mm diameter), special criteria had to be expanded upon for the reconstruction of the area in the dose matrix and for the correct integration of the radioactivity content. PMID- 2254096 TI - Ornithine decarboxylase activity in prostate and tumor: a feasibility study for PET with L-[5-14C]- and L-[5-14C]ornithine. AB - The aim of this study is to investigate the possibility of measuring ornithine decarboxylase (ODC) activity in tissues such as prostate and tumor, by PET. The ODC activity in vitro and the distribution of L-[1-14C]- and L-[5-14C]ornithine were studied in prostate, tumor, liver and kidney. For the animal models, rats bearing Walker 256 carcinosarcoma, were used. Our results indicate that the ODC activity in prostate is correlated with the difference in uptake between L-[1 14C]- and L-[5-14C]ornithine. Measurement of ODC activity in tumor by PET demands a tumor with an ODC activity comparable to that of prostate. Such a tumor will show a sufficient difference in uptake, which can be detected by PET. PMID- 2254097 TI - Synthesis and tissue distribution of four Se-labeled tertiary amines, potential brain pH imaging agents. AB - Four new tertiary amines: bis(3-N,N-dimethyl aminopropyl)selenide (PROMOSE), bis(3-N-(morpholino)propyl)selenide, N-methyl-selenomorpholine and N-phenyl selenomorpholine structurally related to MOSE proposed by Kung and Blau, have been labeled through a radiochemical procedure suitable for both 75Se and 73Se. The radiochemical yields of the carrier added synthesis ranged between 64 and 85% for the four 75Se labelings and was 64% EOB time corrected for [73Se]PROMOSE. The chemical and radiochemical purities were higher than 99% after chromatographic purifications. The n-octanol/phosphate buffer partition coefficients (P) were measured at various pH (6.5-8) for each compound and the tissue distributions of PROMOSE in rats were also carried out. The experimental results showed a good correlation between the P = f(pH) function and the in vivo behaviour of the considered compound. PROMOSE was selected for further investigations as a brain pH indicator. PMID- 2254098 TI - Issue dedicated to Maurice Tubiana. PMID- 2254099 TI - The natural history of breast cancer: implications for a screening strategy. AB - In the data base of the Institut Gustave-Roussy, the clinical courses of over 7000 patients treated since 1951 are registered. For 3000 of them treated prior to the introduction of adjuvant chemotherapy, the follow-up ranges from 15 to 32 years. For all patients, the size of the primary tumor, its histologic grade, and the number of involved axillary nodes at the time of initial treatment were registered prospectively. This series of patients was used to analyze the relationship between the size of the primary tumor and the probability of distant metastatic spread, taking into account other prognostic variables. A simulation model of the natural history of breast cancer was built which satisfactorily fits the available data on breast cancer screening. The aim of this paper is to use this model to assess the influence of: a) the time interval between mammographies and b) the diagnostic ability of the screening program, on the proportion of patients with distant metastases. The results show that the proportion of patients with distant metastases at the time of diagnosis increases gradually from approximately 25% for an interval of 1 year to 40% for an interval of 5 years. Moreover, the proportion of patients with metastases is critically influenced by the size of the tumors which can be detected; for example, for a 2 year interval the proportion of patients with metastases increases from 32% for tumors screened of 1 cm in diameter to 40% for tumors of 1.7 cm in diameter. PMID- 2254100 TI - Evaluation of radiotherapy in high-risk breast cancer patients: report from the Danish Breast Cancer Cooperative Group (DBCG 82) Trial. AB - The role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients included in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82. As of June 1989, a total of 1473 pre- and menopausal patients were randomized to postmastectomy irradiation + CMF versus CMF alone (protocol 82-b). A total of 1202 postmenopausal patients were randomized to postmastectomy irradiation + Tamoxifen versus Tamoxifen alone (protocol 82-c). At 5 years the actuarial loco-regional recurrence rate was significantly lower in the irradiated patients (82-b: 9% vs 28%, 82-c: 6% vs 36%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment (82-b: 54% vs 47%, 82-c: 52% vs 38%). At present, overall survival is significantly different in 82 b patients (68% vs 63%) but not in post-menopausal 82-c patients (62% vs 61%). Thus, adjuvant systemic treatment alone (chemotherapy or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumor control in high risk breast cancer patients with respect to overall survival. PMID- 2254101 TI - Prognostic significance of breast relapse after conservative treatment in node negative early breast cancer. AB - The prognostic significance of local relapse after conservative treatment of early stage breast carcinoma has been controversial. To determine the incidence and the prognostic value of a breast relapse, we analyzed the results obtained in a series of patients with pT1pN0 presentation of breast carcinoma treated conservatively without adjuvant medical treatment. From 1976 to 1986, 202 patients with invasive breast carcinoma of less than 2 cm without lymph node involvement were treated with surgery and radiation therapy. The overall survival rate was 97.2% at 5 years. Locoregional relapses occurred in 16 patients (7.9%). In these patients, the overall survival rate was significantly decreased as compared to that of patients without local relapse (87.5% versus 98.3% at 5 years, p less than 0.001). The probability of remaining metastasis-free was also significantly decreased (80.2% vs 91.3%, p less than 0.001). Most relapses (94%) appeared at or close to the primary site. Salvage local treatment was possible in 14/16 patients (87.5%). Age, menopausal status, size and site of primary tumor, histological grade, and boost technique did not influence significantly the risk of local relapse occurrence. We concluded that the occurrence of a breast relapse after a successful local conservative treatment is a pejorative prognostic factor predictive of a high risk of distant metastasis development. There is a need to individualize factors that could allow discrimination of patients with a high probability of local relapse and subsequent metastasis. PMID- 2254102 TI - The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients. AB - An ongoing randomized study of a specific regimen of hypofractionated radiation therapy (IHF) versus classical or standard radiation therapy (IC) for breast cancer was begun in the Department of Radiation Therapy of the Necker Hospital, Paris France, in January 1982. Breast cancer patients entered into this study received either IC to deliver 45 Gy in 25 fractions over 33 days or a specific IHF regimen to deliver 23 Gy in 4 fractions over 17 days. As of June 1989, 525 patients had been entered into the study. The first 230 patients treated from 1982 through December 1984 had a minimum follow-up of 4 years (range: 4 to 7 years). Preliminary analysis of the results in these first 230 patients are presented. The distribution of patients in this initial group according to clinical staging, associated treatments, and pathological nodes is as follows: T1 = 22%, T2 = 61%, T3 + T4 = 17%, palpable nodes = 28%, inflammatory signs = 7%, surgical treatment = 79% (mastectomy = 35%, tumorectomy + Ir.192 = 44%), radiation alone + neoadjuvant chemotherapy = 21%, N+ = 50% of patients undergoing surgery. Loco-regional recurrences developed in 7% (9/125) of patients in the IHF group and in 5% (5/105) of patients in the IC group. Complications were minor. The addition of the percentage of each complication noted results in a total of 23% for the IHF group and 19% for the IC group (one patient could present several complications). As we had previously observed when comparing these two fractionation regimens in other studies with other tumors, these preliminary results showed no evident difference in the effectiveness and rate of complications whether IHF or IC was used to treat patients with breast cancer. PMID- 2254103 TI - Causes of failure of curative radiation therapy in 205 early glottic cancers. AB - A retrospective analysis of the results obtained with curative radiation therapy in a series of 205 patients affected by early glottic cancer treated from 1970 to 1985 at the Florence University and Hospital Departments of Radiotherapy is presented. All patients were staged according to TNM System (UICC 1978) as T1-T2 NO. The overall 5-year local control rates were 88% for T1a, 75% for T1b, and 64 for T2. The main cause of failure was progression or recurrence in T (41/48); five failures were observed in T and N at the same time and two in N. Of these 48 patients, 21 (44%) were salvaged with surgery. After surgical salvage of radiation failures, the 5-year survival rates were 95%, 91%, and 73%, respectively, for T1a, T1b, and T2. The extent of T and the number of subsites involved significantly affected local control. Vocal cord mobility was less important. The incidence of failures and damages was analyzed according to the radiation beam, the size of the irradiated volume, fractionation, and total tumor dose. PMID- 2254104 TI - Prognostic factors of nasopharyngeal carcinoma: a multivariate analysis. AB - Between 1979 and 1985, 561 patients with nasopharyngeal carcinoma were reviewed to determine prognostic factors that may influence survival. Sex (p = 0.294) and histopathology (p = 0.677) had no correlation to the actuarial survival, whereas the site of cervical metastasis (p = 0.001) and the radiation doses to the nasopharynx and regional lymph nodes (p = 0.03) were both significant when one used univariate analyses. Cox's multivariate regression model revealed that the presence rather than the site of distant metastases was the single most important independent factor influencing the treatment outcome (p less than 0.0001). The addition of chemotherapy, on the other hand, did not show a survival benefit even when one took available confounding factors into account. There are, however, survival advantages associated with: (a) young age (less than or equal to 40 years), (b) asymptomatic status, (c) Stage I or II lesions, and (d) biopsy via nasopharynx instead of neck nodes. These favorable prognostic factors may be used for therapeutic guidance and end-result reporting. PMID- 2254105 TI - Fractionated total body irradiation and bone marrow transplantation in acute lymphoblastic leukemia. AB - From March 1982 to September 1988, 108 patients with acute lymphoblastic leukemia (ALL) were conditioned before allogeneic (57 patients of whom 16 T-depleted) or before autologous (51 patients) bone marrow transplantation (BMT). BMT was realized in 66 patients (31 allogeneic and 35 autologous) in first complete remission (CR) and in 42 patients (26 allogeneic and 16 autologous) in second CR or greater or in relapse. All patients received high doses of alkylating agents prior to a low-dose fractionated total body irradiation of 11 Gy in 5 fractions and 5 days. Rejection and relapse rate are described in relation to the three BMT types, allogeneic non T-depleted, allogeneic T-depleted, and autologous, and to the status of the patient at the time of the transplantation. Leukemic deaths are detailed according to the same parameters. Non-leukemic deaths and complications are determined. For the allogeneic population, the 4-year disease-free survival (DFS) is 47%; it is 68.5% in first CR patients, 23.5% in second or subsequent CR patients, and 50% in T-depleted BMT. For the autologous population, 4-year DFS is 35.7%; it is 52% in first CR patients and 30% in patients in second CR or greater. The conditioning regimen appears to be efficient in terms of disease control with a low rate of complications for the non T-depleted population, transplanted in first CR, but has to be improved for the other patients. PMID- 2254106 TI - Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group. AB - The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy. PMID- 2254107 TI - Combined therapy of localized Ewing's sarcoma of bone: analysis of results in 100 patients. AB - From 1979 to 1986, 182 patients with biopsy proven diagnosis of Ewing's sarcoma of bone were observed. One hundred of the 182 patients (72 males, 28 females, median age 15.8 years) with localized disease and no previous treatment were treated with chemotherapy (VCR, ADM, CTX, D-ACT) for 15-18 months. Local treatment was radiotherapy (42 patients), surgery (31 patients), or a combination of both (27 pts). Radiation doses ranged from 45 to 64 Gy given with conventional fractionation. Median follow-up was 51.2 months (24-106). Overall and disease free survival were, respectively, 58.7 and 42.6%. Resected patients tended to have a better local control (Surgery 93.6%, Surgery + Radiation therapy 92.6%, Radiation therapy 69.1%). Disease-free survival was significantly related to the volume of the primary tumor (bulky: 33.2%, not-bulky: 57.7%), to site (extremities 54.6%, central sites 16.6%, other sites 40.9%), and to local treatment (Radiation therapy 30.3%, Surgery + Radiation therapy 47.9%, Surgery 59.1%). These results are, however, biased because resected patients tended to have smaller tumors in favorable sites. PMID- 2254108 TI - Computed tomography in nasopharyngeal carcinoma: Part I: T-stage conversion with CT-staging. AB - Two hundred seventeen consecutive patients were treated with radiotherapy alone, with curative intent, from 1970 to 1985 at the Radiotherapy Unit of the University and Hospital of Florence. The distribution according to T and N staging with polytomography was compared to patients (106 out of 217) who had CT scans done at presentation. T1 cases were less frequent (6.6% vs 27%) in the CT staged series, whereas T3 showed a higher incidence (30.2% vs 12.6%). The advantages of CT over conventional tomography were quantitated in a subset of 97 patients who underwent both staging procedures. Site-by-site, CT displayed a higher percentage of involvement than polytomography: parapharyngeal spread 18% vs 2%, oropharynx 16% vs 8%, choanae and nasal cavities 28% vs 13%, ethmoid and maxillary sinus 29% vs 13%. Information provided by CT caused a T-stage conversion in 23 out of 97 cases (23%): 4 out of 11 T1, 16 out of 44 T2, 3 out of 16 T3. PMID- 2254109 TI - Computed tomography in nasopharyngeal carcinoma: Part II: Impact on survival. AB - Two hundred and seventeen consecutive patients affected by nasopharyngeal carcinoma (NPC) were treated with radiotherapy alone, with curative intent, from 1970 to 1985 at the Radiotherapy Unit of the University and Hospital of Florence. A group (A) of 111 patients staged with conventional clinical and radiological method was compared to a second group (B) of 106 patients who underwent CT staging before treatment. Group B showed better 5-year NED survival and local control; only the differences in local control were significant (p less than 0.01). As to primary control statistically significant differences were observed in T2 and T4 cases. We feel that CT could have contributed to the improvement, probably through a more reliable display of the primary extent and a more adequately planned radiotherapeutic treatment. With CT staging we could not increase our skills in prognostically separating stages according to UICC criteria (1978); in Group B only T2 patients presented significant differences in primary control when compared to T3 and T4 patients. However, a multivariate analysis of prognostic factors showed that nodal involvement, primarily, and histology, secondarily, were the most important factors; T stage showed a minor influence on prognosis. PMID- 2254110 TI - Cisplatin and radiation: interaction probabilities and therapeutic possibilities. AB - This paper examines the probability of interactions occurring between drug lesions and radiation lesions in DNA for the cytotoxic and radiosensitizing agent cisplatin. The number of cisplatin-induced DNA adducts and radiation-induced strand breaks after a given dose of each agent are known for given cell systems, from which the probability that these lesions will interact can be estimated. Results of these calculations indicate that the probability of interaction could be high, depending on the distance over which two lesions can interact and the probability of repair of the interaction lesion. Calculated lesion numbers have been compared with known data on radiation modification, including illustrations of inconsistencies. In the second part of the paper, ways in which combined therapy with cisplatin and radiation can be improved are described. Development of methods to predict which types of tumor and which individual tumors within a given type are sensitive to the cytotoxic and radiosensitizing effects of the drug would aid rational selection of patients for combination treatments. Immunocytochemical methods sensitive enough to monitor cisplatin-DNA interactions in patients are available and may be useful in this context. The delivery and maintenance of higher tumour concentrations of radiosensitizer offers a further possibility for improvement. Studies of intratumoral injection of cisplatin have shown promise for achieving this goal while limiting normal tissue toxicity. PMID- 2254111 TI - Radiosensitivity of human melanoma spheroids influenced by growth rate. AB - The radiosensitivity of human melanoma cell line BRO was investigated using the multicellular tumor spheroid system. By adding different concentrations of bovine serum to the tissue culture medium, two different growth rates could be obtained. Spheroids (200-250 microns) were irradiated with graded single doses of X rays (2 8 Gy). The radiation response was quantified using specific growth delay, clonogenic cell survival, and spheroid cure. All three assays showed a growth rate dependent radiation response. At both growth rates the spheroid growth fraction and critical cell number were of comparable magnitude. There was a strong correlation between the radiation response of spheroid regenerating units and clonogenic cells from dispersed spheroids. Cell survival curves indicated a decreased ability to accumulate sublethal damage in fast growing multicellular tumor spheroids. From this study it appears that the intrinsic radiosensitivity of human melanoma cell line BRO cells in multicellular spheroids is modulated by intratumoral conditions. PMID- 2254112 TI - Cellular radiosensitivity in V79 cells is linked to alterations in chromatin structure. AB - V79 cells grown as spheroids are more radioresistant than those grown as monolayers. Viable cells from spheroid culture contain restraints to ethidium bromide driven rewinding of DNA supercoils that are absent in monolayer cells. Spheroid cells also contain a DNA-protein matrix that is more resistant to detergent-induced degradation. The increase in structural integrity may be related to a 55-60 kD protein in the nucleoids of spheroid, but not monolayer cells. Spheroid cell radioresistance may therefore be related to a more stable chromatin platform for high fidelity repair of DNA damage. PMID- 2254113 TI - Primary adjuvant whole abdominal irradiation in ovarian carcinoma. AB - Eighty-four patients with an ovarian carcinoma Stage I-III received an adjuvant whole abdominal irradiation (WAI) with pelvic boost postoperatively. Surgery included a bilateral salpingo-oophorectomy, hysterectomy, and omentectomy in 59% of the patients; in 41% surgery was less radical. For the whole abdominal irradiation we used the moving-strip method on 43 patients. The open-field technique was used on the other patients. Median dose of WAI was 22.5 Gy and median pelvic dose was 45.5 Gy. After a median follow-up of 68.5 months, a 5-year survival rate of 64 +/- 5.7% was determined, as well as a 5-year NED rate of 61.2 +/- 5.7%. Five-year survival rate was 80.1 +/- 7.4% in Stage I, 64.1 +/- 9.7% in Stage II, and 35.4 +/- 11.6% in Stage III. Five-year survival depended on tumor rest significantly. There was a trend to better prognosis when surgery was complete and grade was G1 or G2. The risk factor according to Dembo proved to be the most reliable prognostic factor: the 5-year survival rates were 75.0 +/- 6.3% for patients with intermediate risk and 20.1 +/- 10.4% for those with high risk (p = 0.001). Side effects were generally well tolerated. We only saw one serious complication, a radiation-induced small bowel obstruction. PMID- 2254114 TI - Alternating radiotherapy and chemotherapy in non-metastatic inflammatory breast cancer. AB - Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer. PMID- 2254115 TI - Role of radiotherapy in anal preservation for cancers of the lower third of the rectum. PMID- 2254116 TI - Combined chemotherapy--radiotherapy of anal cancer. AB - Forty-five patients were treated from 1984 to 1988. Thirty-eight, with a minimum follow-up of 6 months, are considered evaluable: median age, 62 years (25-88); males 6, females 32; T1 = 7, T2 = 21, T3 = 10; inguinal positive nodes, 5 patients. Chemotherapy (CT) (Mitomycin C, 15 mg/sqm, bolus day 1; 5-FU, 750 mg/sqm, 24 hr infusion, days 1 to 5) and radiotherapy (RT) started the same day. A dose of 36 Gy was given to the tumor and to the pelvis including inguinal nodes, in 20 fractions. After 2 weeks a boost of RT (18 Gy) to the ano-perineal area and a second cycle of CT completed the treatment. CR (biopsy) was achieved in 32/38 patients (84.2%). Among the six patients on PR, four received a Miles operation (2 NED), and two a wide local resection (both NED). Five out of 32 CRs relapsed: 2/5 were rescued with a Miles resection, 3 died from progression. In conclusion, 32/38 patients (84.2%) are NED after a median follow-up of 22 months and 28 of them retained their anal sphincter. A longer follow-up is needed to define optimal treatment modality, but it is clear that surgery must play a minor role in the treatment of anal cancer. PMID- 2254117 TI - Alternate day treatment and late effects: the concept of an effective dose per fraction. AB - Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy. PMID- 2254118 TI - Late tissue reactions after single-fraction sequential half-body irradiation (HBI) in patients with non-Hodgkin's lymphomas. AB - Lung and hepatic toxicities constituted the main radiation-related damage after half-body irradiation (HBI) used as the treatment for patients with non-Hodgkin's lymphomas (NHL). Liver damage was mostly transient after a single dose of 8 Gy and could be well monitored by serum enzyme levels. A dose-response relationship could be shown for lung damage in the single dose range of 6.25-9.25 Gy, but the relationship did not reach statistical significance. A significant dose-rate effect could be shown. Mediastinal involvement by lymphoma seemed to increase the risk of pneumonitis. In a radical setting half-body irradiation is recommended to be used at a low dose-rate or as a multifraction irradiation in order to reduce the risk of liver and lung toxicities. PMID- 2254119 TI - Uncertainties in dosimetric data and beam calibration. AB - Recent studies indicate that the calibration of therapeutic beams is one of the main sources of uncertainty in the mean absorbed dose to the target volume in radiotherapy. Interaction coefficients and data used through the different steps in the calibration are pointed out as the main contribution to this uncertainty. Procedures used to select dosimetric data, that is, input parameters used in the specification of the quality of the beam, cause another contribution. In this paper the actual status of the data used for the dosimetry of photon and electron beams is introduced first. Uncertainties along the dosimetric chain are analyzed according to the procedure and data used in recent publications. Uncertainties in stopping-power ratios, considered the main contribution, are discussed in detail starting from the basic electron stopping-power data. Overall uncertainties in the presently available set of stopping-power ratios are analyzed. Recent developments in the dosimetry of electron beams, related to the effect of energy and angular spread and electron and photon contamination, are discussed in connection with the procedure to select stopping-power ratios for clinical dosimetry. Uncertainties along the dosimetric chain are evaluated in terms of the present knowledge of error sources. PMID- 2254120 TI - Supporting cancer care in the developing countries: role of IAEA/WHO. AB - Cancer management can be expensive and constitutes a major problem in many developing countries where management standards are poor due to many factors, including non-availability of sufficient funds, equipment, and trained personnel. The incidence of cancer is rising worldwide. This is more so in the developing countries, many of whom are less equipped to deal with the problems. Radiation therapy is one of the major treatment modalities for cancer, and it is estimated that about 60% of all cancer patients require this treatment at one time or another during the course of their disease. Unfortunately, radiotherapy facilities are lacking or grossly inadequate in many developing countries. Over the past 8 years the IAEA and WHO have shown more interest in the problem and treatment of cancer in the developing countries. This paper reviews the role of these international organizations, with emphasis on research activities, education (seminars, workshops, training courses), and technical assistance programs. These include establishment or upgrading of radiotherapy facilities, provision of experts, etc. Scientific papers are published with a view to disseminating current information and research findings in the developing countries. The achievements up to date are assessed and discussed. PMID- 2254121 TI - An overview of the situation in radiotherapy with emphasis on the developing countries. AB - Radiotherapy services are closely linked to the level of medical care which, in turn, is an important component of the overall health care program, with its development related to social, economic, and educational factors. As a basis for understanding the situation regarding adequate coverage of the population by radiotherapy services, general information about the world population (currently 5 billion), age distribution, frequency of cancer occurrence, and causes of death is presented. For an appreciation of the obstacles that must be overcome, the situation with regard to Gross National Product (GNP), transfer of economic resources, and per capita expenditures for health services is shown. For example, in the developing world, most countries spend less than 5% of their GNP for health, and on a macro scale at least 20 billion U.S. dollars per year are being transferred from the poor nations of the southern hemisphere to the northern hemisphere. Information about the wide range of population coverage with radiotherapy resources and the trend regarding high-energy radiotherapy machines is presented. For example, in North America (USA) there are six high-energy machines for each one million persons, and each machine is used to treat about 230 new patients per year. In other parts of the world, such as large areas of Africa and South-East Asia, there may only be one high-energy radiotherapy machine for 20 to 40 million people, and one machine may be used to treat more than 600 new patients per year. Many cancer patients have no access to radiotherapy services. When estimates of the need for radiotherapy services in the developing world as a consequence of cancer incidence are compared with the current health expenditures, it is concluded that a combined effort of national authorities, donor and financial institutions, professional and scientific societies, and international organizations is required. The knowledge, skills, and technology are available in many excellent radiotherapy centers throughout the world. The key issues are priority and the commitment of sufficient resources. PMID- 2254122 TI - An overview of cancer management by radiotherapy in Anglophone West Africa. AB - The problems associated with cancer management particularly by radiotherapy in the developing countries are well known. This paper attempts to present the case as it is in Anglophone West Africa, and to quantify the severity of the problem through a critical analysis of available data based on the experience at the oldest radiotherapy center in West Africa between January 1981 and December 1988. In the whole of the Anglophone West African states with a population estimated at 140 million people, there was only one functional radiotherapy center until 1986 when another unit was commissioned. The paper analyzes the types of tumors managed, radiotherapy facilities available, staffing, and the other operational problems encountered by the Radiotherapy Department of the Lagos University Teaching Hospital in Nigeria. Suggestions are made for the overall improvement of radiotherapy services in the region. PMID- 2254123 TI - Situation of radiotherapy in Latin America. AB - A survey to evaluate situation of radiotherapy in Latin America was conducted. Consultation was made with representatives of 10 countries, resulting in the responses of 5. These five countries represent around 80% and 81%, respectively, from the total area and population of South America. Situation of equipment, modern facilities, and human resources is analyzed. A Cobalt machine is the basic megavoltage equipment in Latin America; half of the total number, however, is of old units with very low output sources. Linacs represent one-third of cobalt machines, the majority of low photon energy without electron capability. Treatment planning, localization, patient positioning, and immobilization are inadequade or of low quality in a high number of institutions. Teaching programs are insufficient or inexistent in certain areas. Late diagnosis and referral for treatment is a major problem for cancer control in Latin America. Hierarchization and regionalization of radiation therapy centers are indicated as a way to provide high quality services and teaching programs. In Latin America, lodging and facilities for transportation are essential to assure the continuity of radiation treatment and regular follow-up to patients from rural or distant areas. PMID- 2254124 TI - The radiotherapy situation in Thailand and South East Asia. AB - The situation of radiotherapy in Thailand from its beginning to the present is reported. The situation of radiotherapy in other countries of South East Asia is also analyzed from the data or information requested through the Radiological Society of each country. The situation of radiotherapy in each country will be discussed in terms of equipment, facilities, personnel, teaching and training, research, and clinical practices. In each country, efforts have been made to develop radiotherapy facilities so that services can be given at a modern standard. Some countries has attained that standard and full range of radiotherapy has been available. An effort has been made to help each other and exchange knowledge by organizing the Asian and Oceanian Society of Radiology (AOSR) and the Asian Association of Radiology (AAR) through which Congress of Radiology has been organized every 2 alternate years. PMID- 2254125 TI - National training of radiotherapists in Sri Lanka and Zimbabwe: priorities and strategies for cancer control in developing countries. AB - The development of therapy resources should not be done in isolation of other cancer control activities. The right priorities and strategies must be determined in a systematic way, preferably through well-conceived national cancer control programs. If this is not done, it is unlikely that the therapy efforts will have any impact on cancer in the developing countries, as most cancers are incurable when seen for therapy. Therapy efforts must be linked with the search for earlier referral and diagnosis of cancer patients. However even limited resources may have an effect on controlling cancer, provided that the right priorities and strategies are followed. National and regional training facilities with a suitably adapted syllabus in radiotherapy and oncology must be a part of these priorities and strategies. The World Health Organization (WHO) has initiated, in close collaboration with the National Governments, national and regional training courses in radiotherapy and oncology in Sri Lanka and Zimbabwe. PMID- 2254126 TI - Total body irradiation regimens for marrow grafting. PMID- 2254127 TI - The role of marrow grafts in irradiation accidents. PMID- 2254128 TI - Second primary tumors following radiotherapy for childhood cancer. AB - Among a cohort of 9,279 survivors of childhood neoplasms other than retinoblastoma treated in Britain before 1980, the cumulative risk of a second primary tumor (SPT) by 25 years from 3-year survival was 3.7%. This corresponds to about five times the number expected from rates of cancer occurring in the general population. In the absence of both radiotherapy and chemotherapy, there was four times the expected number of subsequent cancers. The risk of an SPT associated with radiotherapy but not chemotherapy and both radiotherapy and chemotherapy were 6 and 9 times that expected, respectively. There is evidence that radiotherapy was involved in the development of many of the SPT's observed. However, case-control investigations are required to examine the relationship between relative risk of an SPT and therapy in detail. Secondary leukemia appears to occur more frequently among more recently diagnosed children with cancer. It is important to continue to monitor the occurrence of SPT's with a view to identifying the least carcinogenic therapies that are consistent with not compromising survival prospects. PMID- 2254129 TI - Cancer occurring after radiotherapy and chemotherapy. AB - Radiotherapy and chemotherapy can effectively control cancer but can also cause new cancers to develop as long-term complications. Almost all types of cancer have been associated with radiotherapy. The breast, thyroid, and bone marrow are the organs most susceptible to radiation carcinogenesis. The bone marrow is also most frequently involved by chemotherapy and the leukemia risk is much higher than after radiotherapy. The combination of intensive radiotherapy and chemotherapy is particularly leukemogenic. The latent period between radiotherapy/chemotherapy and the appearance of a second primary cancer ranges from a few years to several decades. The risk for a second primary cancer following radiotherapy or chemotherapy emphasizes the need for life long follow up of patients receiving such treatments. This is particularly the case in individuals with long life expectancy, for example, patients treated for childhood neoplasms. The benefits of radiotherapy and chemotherapy in oncology exceed the risks for second primary cancers. Efforts should be directed towards identifying those patients who will benefit from the treatments so that only they are exposed to the risk. PMID- 2254130 TI - Anal cancer. AB - Combined modality treatment with radiation, chemotherapy, and conservative surgery controls most epidermoid cancers of the anal canal and advanced squamous cell cancers of the perianal skin. Anorectal function is preserved in about 70% of patients or more. Five-year survival rates are similar to those previously obtained with radical surgery or radical radiation therapy. The cytotoxic drugs 5 Fluorouracil and Mitomycin C are frequently given concurrently with radiation, but other effective regimens have also been described. The mechanisms of interaction of radiation and cytotoxic drugs in the treatment of anal cancer are not known. PMID- 2254131 TI - The rationale for continuous, hyperfractionated, accelerated radiotherapy (CHART). AB - Continuous, hyperfractionated, accelerated radiotherapy (CHART) was devised to give the maximum chance of improving clinical radiotherapy and was based upon available radiobiological evidence. A pilot study, begun in 1985, has now included 210 patients. When comparison is made with previously treated cases, improved results have been seen in the two main groups included, that is, advanced head and neck and bronchial carcinomas. Multi-center randomized controlled clinical trials are planned. PMID- 2254132 TI - Influence of conditioning on the outcome of allogeneic bone marrow transplantation. AB - Allogeneic bone marrow transplantation is widely used for the treatment of various hematologic disorders. The results are quite reproducible from center to center with a mean disease-free survival of 50%, which varies from 10% in patients transplanted in relapse to 70% in young patients transplanted in first complete remission or in the chronic phase of chronic myeloid leukemia. Relapse is one of the main complications, and its frequency increases with disease status and the use of T cell depletion and the subsequent loss of the graft versus leukemia effect of transplanted allogeneic cells. New agents such as high dose ARA-C, VP 16, Myleran, and Melphalan have been studied in Phase I-II studies. Different modalities of total body irradiation, that is, single dose or fractionated or hyperfractionated doses, have been used. None of these new modalities has modified significantly the long-term disease-free survival rate because of the toxicity of any attempt to diminish the rate of relapse with intensified regimens. Single dose total body irradiation of 10 Gy seems to reduce the risk of leukemic relapse when compared with 12 Gy fractionated total body irradiation, especially when the marrow is T depleted. PMID- 2254133 TI - Fractionation: a panoramic view. PMID- 2254134 TI - Surgery by nonveterinarians. PMID- 2254135 TI - Testing for exocrine pancreatic insufficiency in cats. PMID- 2254136 TI - Veterinary services for animal use in the United States: a conflict of paradigms. PMID- 2254137 TI - The liability potential for laboratory animal and public veterinarians. PMID- 2254138 TI - Study design. PMID- 2254139 TI - ECG of the month. PMID- 2254140 TI - Give it your best shot. PMID- 2254141 TI - Atracurium administration, as an infusion, to induce neuromuscular blockade in clinically normal and temporarily immune-suppressed cats. AB - Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered by infusion to 10 cats that were anesthetized with isoflurane and oxygen to allow transplantation of a myocutaneous flap. Five of the cats were given cyclosporine (20 mg/kg of body weight, PO q 12 h in divided doses) for 2 days prior to anesthesia, and prednisolone (0.25 mg/kg, PO) on the morning of surgery. The other 5 cats were not given either drug. Neuromuscular blockade was assessed, using the train-of-four stimulation, and throughout surgery, the infusion rate was adjusted to maintain the first-twitch response (T1) at 90 to 95% depression from baseline. At completion of surgery, atracurium was discontinued, and the infusion rate and the time for recovery (the time for the train-of-four ratio to increase from 50 to 75%) were recorded. Once the train-of four ratio had been stable for 10 minutes, edrophonium (0.5 mg/kg), a cholinesterase inhibitor, was administered IV, and neuromuscular blockade was monitored for another 10 minutes. Mean (+/- SD) duration of the atracurium infusion was 302.1 +/- 70.5 minutes for the control group and was 323.9 +/- 61.7 minutes for the cats given cyclosporine and prednisolone. In the cats of the control group, the infusion rate required to induce 90 to 95% T1 depression from baseline was 3.7 +/- 0.7 micrograms/kg/min. This rate was not significantly different from that of 2.8 +/- 1.2 micrograms/kg/min in cats given cyclosporine and prednisolone. Significant difference in recovery time was not evident between the control group and the treated group (6.4 +/- 4.5 minutes vs 6.2 +/- 2.5 minutes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254142 TI - Endometrial biopsy technique and uterine pathologic findings in llamas. AB - Uterine tissue specimens from 90 llamas with history of infertility were examined and graded microscopically; 83 specimens were obtained by endometrial biopsy and 7 specimens were obtained at necropsy. Fifteen llamas (16.7%) had a normal uterus, which was graded 1A. Twenty-three llamas (25.6%) had minor uterine abnormalities that were graded 1B. Forty-five llamas (50.0%) had appreciable endometritis that was graded 2A. Three llamas (3.3%) had endometritis with gland fibrosis that was graded 2B. Two llamas (2.2%) had notable uterine gland fibrosis that was graded 3A. Two llamas (2.2%) had uterine neoplasia that was graded 3B. Thirty-six llamas had follow-up evaluation; 22 became pregnant, most after some form of treatment. Uterine biopsy in llamas was readily performed without complications and was valuable in identifying a wide range of uterine diseases, most of which were amenable to treatment. PMID- 2254143 TI - Clinical and electrocardiographic characterization of cattle with atrial premature complexes. AB - Atrial premature complexes (APC) were identified in 16 cows over a 2-year period. Fourteen cows had concurrent gastrointestinal disease. Variation in the intensity of the first heart sound and an occasionally irregular heart rhythm were evident during thoracic auscultation. Neither cardiac murmurs nor pulse deficits were detected in any cows, and clinical signs of heart failure were lacking. Three cows had APC immediately prior to or after development of atrial fibrillation. The heart rate when APC were diagnosed ranged from 48 to 124 beats/min (mean, 77 +/- 20 beats/min), and the APC frequency ranged from less than 1 to 23/min (mean 9.4 +/- 8.0). The P-wave morphologic characteristics in 4 cows with APC was abnormal. The coupling index of the APC varied between 0.44 and 0.95, with a mean of 0.73. Aberrant ventricular activation was usually associated with a short coupling interval (coupling index less than 0.60) and was observed in 3 cows. Ten cows were determined to be hypocalcemic and 4 cows hypokalemic when APC were identified. Atrial ectopic activity could not be detected in 12 cows after resolution of the concurrent gastrointestinal disorder or electrolyte abnormality. Atrial premature complexes may be a functional cardiac disorder in cattle, unrelated to structural heart disease. The potential for APC to progress to sustained atrial arrhythmias such as atrial fibrillation should be considered. PMID- 2254144 TI - An Eperythrozoon-like parasite in llamas. AB - An Eperythrozoon-like RBC parasite was found in a herd of llamas in western Kentucky. The light microscopic and electron microscopic features of the organism were similar to those of E suis. Results of an indirect hemagglutination test for E suis were positive with sera from some parasitemic and nonparasitemic llamas. Parasitemic llamas were usually less than 1 year old and had more severe clinical signs of disease than did older llamas. Poor weight gain and growth, anorexia, and prolonged recumbency were the principal signs of disease. Anemia was usually mild and not accompanied by icterus. Hypoglycemia was associated with parasitemia. Some response to oral or parenteral treatment with tetracycline was noticed, but recrudescence of the infection in some treated llamas was observed. Llamas in nearly every region of the United States have had titers in approximately 12% of samples tested, suggesting that infection with the organism may be widespread. Parasitemic llamas have been recognized in at least 8 states. PMID- 2254145 TI - Tyzzer disease in hamsters and gerbils from a pet store supplier. AB - An episode of Tyzzer disease (Bacillus piliformis) developed in hamster and gerbil colonies of a pet store supplier. The incidence of diarrhea and subsequent mortality was high. The only important necropsy findings were cecal distention and mesenteric lymphadenopathy in the hamsters. Histologically, necrotizing typhlitis and hepatitis with associated B piliformis organisms were seen in both species. This case was unusual because the most consistent gross lesion associated with Tyzzer disease--hepatomegaly with multiple pale foci of hepatic necrosis--was not seen. Tyzzer disease is widespread geographically and among species; B piliformis has been reported to cause disease in at least 18 species of animals including hamsters, gerbils, rabbits, guinea pigs, horses, cows, dogs, and cats. Clinical signs of disease are nonspecific, and treatment is difficult because the organism is intracellular, although tetracycline and oxytetracycline reportedly have controlled mortality. PMID- 2254146 TI - Pharyngeal mucocele and respiratory distress in a cat. AB - A young cat was referred to an emergency clinic for acute onset of respiratory distress. Physical examination revealed right submandibular, sublingual, and pharyngeal swellings, presumably of salivary origin. Respiratory arrest necessitated emergency tracheostomy and resection of pharyngeal mucocele. PMID- 2254147 TI - Polypoid cystitis, pyelonephritis, and obstructive uropathy in a cow. AB - Polypoid cystitis, pyelonephritis, and obstructive uropathy was found in a cow with hematuria, dysuria, and colic. The cow was treated with penicillin, multiple B vitamin supplementation, and isotonic sodium chloride. Polypoid cystitis, diagnosed in this cow by use of endoscopic examination, is a common response to chronic inflammation of the bladder and can lead to obstructive uropathy. Although endoscopic confirmation of this diagnosis may not always be feasible, recognition of corresponding clinical signs can allow timely, appropriate treatment. PMID- 2254148 TI - Condylar buttress plate fixation of femoral fracture in a colt. AB - A Salter-Harris type-II fracture of the distal portion of the femur in a 1-year old Pony of America was repaired by use of lateral plating combined with interfragmentary compression. The configuration of the fracture and the method of internal fixation with a condylar buttress plate were unique and resulted in primary bone healing, seen at the 5-month follow-up examination. PMID- 2254149 TI - Mediastinal squamous cell carcinoma and thyroid carcinoma in an aged horse. AB - A mediastinal squamous cell carcinoma and thyroid carcinoma were found in an aged horse. Clinical signs consisted of bilateral thyroid gland enlargement, chronic cough, and mild respiratory distress. The neoplasms were not treated. Squamous cell carcinoma is a common neoplasm in horses, but not in the cranial portion of the mediastinum. Thyroid carcinomas in horses are uncommon. This combination of neoplasms is rare and may have been associated with a defect in the immune system. PMID- 2254150 TI - Displacement of the large colon associated with nonsurgical correction of large colon entrapment in the renosplenic space in a mare. AB - Nonsurgical correction of a renosplenic entrapment of the large colon was attempted in a mare, using a rolling technique. After correction, the mare had initial improvement in clinical signs, but later developed signs of abdominal discomfort. A ventral midline celiotomy was performed, and a pelvic flexure impaction and large intestinal volvulus were found and corrected. PMID- 2254151 TI - Pleural effusion secondary to thoracic metastatic mammary adenocarcinoma in a mare. AB - A 17-year-old Quarter Horse mare was examined nearly 3 years after excision and cryotherapy of a papillary mammary gland adenocarcinoma. The mare had been used for pleasure riding since surgery, but had recently developed progressive dyspnea. The mare had clinical evidence of pleural effusion, but died before further clinical examination and treatment were instituted. Necropsy revealed deep mammary masses with similar nodules in the deep inguinal, renal, and mediastinal lymph nodes and in the lungs, pericardium, visceral and parietal pleurae, and left ovary. The masses were identified as papillary mammary gland adenocarcinoma. Large volumes of free pleural and peritoneal fluid were detected. The pleural fluid contained similar neoplastic cells that could have been readily detected by exfoliative cytologic examination had the mare survived. PMID- 2254152 TI - Iatrogenic fractures of ribs and vertebrae during delivery in perinatally dying calves: 235 cases (1978-1988). AB - To determine the pathogenesis of vertebral fractures in calves during the perinatal period, a retrospective study was done to determine the relationships between clinical factors at dystocia and the findings during necropsy of 235 perinatally dying calves. It was concluded that excessive traction is the most important cause of rib and vertebral fractures in the calf during dystocia. Vertebral fractures in perinatally dying calves may not be simply judged as a sign of asphyxia. The occurrence of vertebral fractures is highly correlated with the type of delivery and the force of traction. The veterinarian as well as the type of calf also are influencing factors. More perinatally dying calves were delivered after hips were locked, when extraction had been forced, or through induction of trauma when the head of the calf had the pelvic canal during the first obstetric examination. Consequently, fetal position at delivery may predispose calves to risky extractions and to the risk of perinatal death secondary to trauma. In light calves, significantly more vertebral fractures occurred during extractions than in other calves. Therefore, the veterinarian should accurately estimate the birth weight of the calf and the force of traction that should be applied. PMID- 2254153 TI - Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988). AB - We reviewed the medical records of 494 cats with a variety of nonthyroidal diseases in which serum thyroxine (T4) concentration was determined as part of diagnostic evaluation. The cats were grouped by category of disease (ie, renal disease, congestive heart failure, diabetes mellitus, focal neoplasia, systemic neoplasia, hepatopathy, inflammatory bowel disease, inflammatory pulmonary disease, miscellaneous diseases, or undiagnosed disease), degree of illness (ie, mild, moderate, or severe), survival (ie, lived, died, or euthanatized), and presence or absence of a palpable thyroid gland. The mean (+/- SD) serum T4 concentrations in all 10 groups of cats, which ranged from 10.5 +/- 11.1 nmol/L in cats with diabetes mellitus to 18.7 +/- 7.8 nmol/L in cats with focal neoplasia, were significantly (P less than 0.001) lower than those of normal cats (27.0 +/- 10.4 nmol/L). The number of ill cats with low serum T4 concentrations (less than 10 nmol/L) was highest in the cats with diabetes mellitus (59%), hepatopathy (54%), renal failure (48%), and systemic neoplasia (41%). When the serum T4 concentrations in cats with mild, moderate, and severe illness were compared, mean concentrations were progressively lower (21.3 +/- 6.8, 14.8 +/- 8.1, and 6.5 +/- 5.8 nmol/L, respectively) as degree of illness increased. Severity of illness had a more significant (P less than 0.001) effect in lowering serum T4 concentrations than did disease category. Mean serum T4 concentrations in the cats that died (7.8 +/- 9.8 nmol/L) or were euthanatized (10.0 +/- 7.0 nmol/L) were also significantly (P less than 0.001) lower than those of cats that survived (15.2 +/- 8.8 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254154 TI - Pharmacologic features and physiologic effects of dopamine. PMID- 2254155 TI - What is your diagnosis? Diffuse bronchointerstitial pattern consistent with a pulmonary infiltrate. PMID- 2254156 TI - Postnatal development of the hair cycle in the domestic pig. AB - The postnatal patterns of hair follicle activity have been quantified in pigs born in summer and winter. Animals were skin sampled monthly during the first year of life and the stages of the hair cycle were identified from follicles in histological sections. Percentages of active follicles were used to determine hair cycle patterns and as a measure of how the hair cycle became synchronised with that of the adult. At birth, in excess of 95% of follicles were active in fibre production. Within the first 12 weeks of life, the proportions of active follicles were found to approach those found in adult skin, and thereafter the hair follicle population of the growing pig displayed cycles of activity and rest reminiscent of those of the mature animal. PMID- 2254157 TI - An immunohistochemical study of the distribution of matrical proteins in the mandibular condyle of neonatal mice. I. Collagens. AB - This study provides new information concerning the distribution of cartilage collagens in neonatal mammalian condylar cartilage. It became apparent that young cartilage cells contain pro-Type I collagen as well as pro-Type II collagen. The mature molecule of Type I collagen appears only in the extracellular matrix of the mineralisation zone close to the ossification front. Type II collagen, on the other hand, is apparent throughout the extracellular matrix as soon as the chondroprogenitor cells have differentiated into chondroblasts. In addition, Type II collagen is noticed in the core of the newly formed bone trabeculae within the primary spongiosa. Type IX collagen was found to be co-distributed with Type II collagen in cartilage and bone. Hypertrophic chondrocytes within the mineralisation zone, but in no other zone, demonstrate an intense reactivity for Type X collagen. Mild reactivity throughout the condylar process is encountered with regard to Type VI collagen. Perichondrium but not cartilage reacts positively for Type III collagen. PMID- 2254158 TI - Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. AB - Biopsies of histologically normal adult human cerebral cortex, underlying white matter and overlying leptomeninges were taken from frontal and temporal lobectomy specimens excised during the removal of cerebral tumours. Multiple blocks from 6 patients (aged 18-53 years) were examined by light and transmission electron microscopy. A thin sheath of pia mater cells was found to surround completely arterioles and arteries in the brain, in the subpial space and in the subarachnoid space. Pia mater cells, forming the perivascular sheath, were identified by the presence of desmosomes or small nexus junctions and by continuity with the pia mater itself. The presence of the pial sheath suggests that the perivascular spaces around intracerebral arteries are in direct continuity with the perivascular spaces around subarachnoid arteries. No similar pial sheath was observed around intracerebral or subpial venules. The role of the periarterial spaces, enclosed by the pial sheath, is discussed in relation to the results of physiological experiments suggesting drainage of interstitial fluid from brain tissue into the perivascular pathways along major cerebral arteries in the subarachnoid space. As arterioles in the brain become smaller and lose their smooth muscle coats, the pial sheath becomes incomplete. The anatomical relationships between the pia mater and blood vessels in the human cerebrum is summarised diagrammatically, and a possible role for pial cells as an enzymic barrier protecting the brain from exogenous catecholamines is discussed. PMID- 2254159 TI - High density of nodes of Ranvier in the CNS-PNS transitional zone. AB - Node of Ranvier density was examined at three levels along rat lumbar motoneuron axon bundles: where they lie in the central nervous system, in the peripheral nervous system and in the transitional zone (TZ) between these. Density was considerably and significantly greater in the TZ than in either of the other locations. It is possible that such densely packed nodes in the TZ could interact electrically with one another. Because of its structure and position and because it contains a relatively pure fibre population, the rat L4 ventral rootlet TZ lends itself readily to electrophysiological investigation of this possibility. PMID- 2254160 TI - An enzyme histochemical study of large muscle fibres in the neonatal mouse. AB - Small clusters of extra large muscle fibres were identified in hindlimb muscles of neonatal mice (strain C57BL/10ScSn). At two days of age they had a significantly greater cross-sectional area than their normal counterparts (P less than 0.01). Fibre typing methods (NADH-tetrazolium reductase, ATPase and phosphorylase) classified them as 2A fast oxidative glycolytic (FOG fibres). The activity of NADH-tetrazolium reductase and the lysosomal enzymes beta glucuronidase, acid phosphatase and dipeptidyl peptidase II were all elevated in the large fibres. Microsomal aminopeptidase (mAPP), a membrane-bound enzyme, also showed increased activity. The fibres are probably the mouse equivalent of the Wohlfart B fibres of the human fetus, with which comparison is made. PMID- 2254161 TI - Synapse-to-neuron ratios in rat cerebellar cortex following lengthy periods of undernutrition. AB - Black and white hooded Lister rats were undernourished for various times up to 150 days of age; some of them were nutritionally rehabilitated from 75 days. Undernourished rats weighed significantly less than well-fed controls at all ages studied. After embedding in resin, sections of cerebellar cortex were cut and examined at the light and electron microscopical levels using traditional morphometric methods. Undernourished rats showed significant deficits in synapse to-neuron ratio, compared with controls, at 21 days of age. This deficit disappeared by 75 days despite continued undernutrition. Indeed, there was no alteration in this ratio even when undernutrition was extended up to 150 days even though the ratio for the controls decreased after that period. Rats undernourished from birth to 75 days and subsequently rehabilitated to 150 days had significantly more synapses per neuron than controls. The functional sequelae of these morphological changes remain unknown. PMID- 2254162 TI - The three-dimensional structure of the musculature and the nerve elements in the rabbit ureter. AB - The three-dimensional arrangement of muscle fibres and nerve elements in the rabbit ureter was examined by scanning electron microscopy after removal of fibrous elements by the HCl-trypsin digestion method. The ureteral muscle coat consisted of an interlacing network of muscle bundles made up of varying numbers of smooth muscle cells. On the outer surface of the muscle coat the muscle bundles predominantly extended transversely but some of them continued longitudinally. Some small bundles diverged from the main bundle and joined up with neighbouring or distant bundles. In most regions of the muscle coat irregular membranous or bifurcating cells were sometimes observed. On the longitudinally cut surface of the ureter, polygonal profiles of the cross sectioned cells and elongated profiles of the longitudinally-sectioned cells were observed in the same bundle. The variety of these cut profiles suggested the differing directions of the muscle Some small interconnecting bundles extended across the inter-bundle spaces. Neighbouring muscle cells were connected laterally by short processes and were joined by gap junctions and desmosomal junctions; these were seen by transmission electron microscopy in thin sections and by freeze-fracture replicas. Thread-like nerve fibres were seen to be lying individually or in a fasciculus. Their terminals were characterised by varicose swellings. Streaks indicting mesaxonal extensions were exhibited on the Schwann cells enclosing nerve fibres. PMID- 2254163 TI - Nerve supply of the human vastus medialis muscle. AB - Dissection of 30 human vastus medialis muscles and their nerves has revealed a consistent bipartite nerve supply from the posterior division of the femoral nerve. One part, a short and slender nerve termed the lateral branch, supplies the upper lateral portion of the muscle. The other part, a medial branch, supplies the middle and lower portion of the muscle. There is a distalward increase in the numbers of nerve fibres supplying the muscle, with the lowermost muscle fibres receiving the richest nerve supply. The detailed connections of the two nerves of the vastus medialis were traced to the lumbar plexus in three cadavers. The lateral branch receives fibres from the lower roots which contribute to the femoral nerve (L3 and 4), while the medial branch, which supplies the middle and lower parts of the muscle, receives its fibres from higher segments of the lumbar spinal column (L1, 2 and 3). The lateral branch, which in some cases arises from the nerve that supplies the vastus intermedius, receives a similar spinal input to that of the vastus intermedius. Therefore, whereas the upper portion of the human vastus medialis muscle is closely aligned with the vastus intermedius, the lower third of the muscle has a richer innervation and also shows a distinct gross morphology that, among primates, may be unique to humans. The gross structure of the muscle, taken together with this evidence from the pattern of innervation, suggests that the human vastus medialis is functionally tripartite. PMID- 2254164 TI - The superficial origin of the trochlear nerve with special reference to its vascular relations. PMID- 2254166 TI - Proceedings of the Anatomical Society of Great Britain and Ireland. 19-21 December 1989. Abstracts. PMID- 2254165 TI - Proceedings of the Anatomical Society of Great Britain and Ireland. Papers presented at the symposium on Multidimensional Morphology Analysis held during the summer meeting of the Society. 11-13 July 1989, Liverpool. Abstracts. PMID- 2254167 TI - An immunohistochemical study of the distribution of matrical proteins in the mandibular condyle of neonatal mice. II. Non-collagenous proteins. AB - This study has illustrated the localisation of several non-collagenous proteins in the extracellular matrix of neonatal condylar cartilage (chondrocalcin, proteoglycans and a 100 kDa protein). Also, it has been shown that chondrocytes synthesise laminin and anchorin CII. The bone trabeculae in the primary spongiosa reacted positively for chondrocalcin, osteopontin and BMP. The cartilaginous wealth of collagens (Type I, II, VI, IX, X and XI), together with the various non collagenous proteins, are considered to possess an important role in the maintenance of chondrogenic expression as well as in the regulation of cartilage differentiation by means of an interaction with the undifferentiated precursor cells. PMID- 2254168 TI - An ultrastructural study of the development of astrocytes in the midbrain of the lizard. AB - Astrocyte development was investigated electron microscopically in the midbrain of the lizard Gallotia galloti from E32 to adult. At E32 only very immature (early) glioblasts were present in the midbrain and similar cells could be found until hatching. From E34 two other types of glioblast could be identified--dark glioblasts which had a slightly greater amount of cytoplasm than early glioblasts and light glioblasts, in which cytoplasmic organelles were more abundant. Both dark and light glioblasts were present in very small numbers in the adults. Astroblasts, which could be identified by the characteristic appearance of their rough endoplasmic reticulum, first appeared at E35, at which stage a few very immature astrocytes containing small quantities of gliofilaments were also present. With increasing age the quantity of gliofilaments in astrocyte cytoplasm increased. Astrocytes in the adult white matter contained very large amounts of gliofilaments whereas those in grey matter contained many fewer gliofilaments and had glycogen granules in their cytoplasm which were rarely present in mature fibrous astrocytes. PMID- 2254169 TI - An ultrastructural study of the development of oligodendrocytes in the midbrain of the lizard. AB - Oligodendrocyte development was investigated in the midbrain of the lizard Gallotia galloti using the electron microscope. Oligodendroblasts, which had a pale cytoplasm containing numerous microtubules in the perikaryon and processes, were present from E35. Active oligodendrocytes had a pale nucleus, usually containing a nucleolus, and an electron-dense cytoplasm with long parallel stacks of rough endoplasmic reticulum. These were present from E37 to hatching which coincides with the period of rapid myelination. The three types of oligodendrocyte (light, medium and dark) first classified by Mori & Leblond (1970) in the rat could be identified in the lizard. Light oligodendrocytes were present at all ages from E37 to adult. Medium oligodendrocytes first appeared at E40 and dark oligodendrocytes were present at all ages from hatching onwards. PMID- 2254170 TI - Distribution of acetylcholinesterase in the nerve endings of chicken m. retractor phalli cranialis. AB - The distance of the neuromuscular gap was measured in a chicken smooth muscle, m. retractor phalli cranialis (MRPC). For the identification of active neuromuscular contacts, acetylcholinesterase (AChE) was stained according to Tago's modification of the Karnovsky and Roots' method. Thirty two out of 500 muscle cells were within 200 nm from the nerve endings. The MRPC was classified as Burnstock's Model C, which is characterised by the low frequency of directly innervated cells. The AChE-positive reaction was observed on both muscular and neural membranes only when the distance between the two was less than 170 nm. These results suggest that the smooth muscle cells may be innervated by axon varicosities within such a distance. PMID- 2254171 TI - An immunohistochemical study of endocrine cells of the alimentary tract of the King's skink (Egernia kingii). AB - The gastrointestinal tract of the King's skink (Egernia kingii) was examined for the presence of fifteen regulatory peptides, two proteinases and an amine by immunohistochemical methods. Immunoreactivity was detected for somatostatin, gastrin, motilin, bovine pancreatic polypeptide, pepsinogen and serotonin, but not for avian pancreatic polypeptide, gastric inhibitory peptide, secretin, cholecystokinin, enteroglucagon, pancreatic glucagon, gastrin-releasing polypeptide, neurotensin, vasoactive inhibitory polypeptide, leu-enkephalin or chymosin. The six peptides detected in E. kingii have been previously found in the gastrointestinal tract of squamate reptiles; however, immunoreactivity for other peptides previously detected in squamates, in particular another skink, was not observed. In addition, chromogranin was found to be effective in the detection of endocrine cells though its specificity was unknown. PMID- 2254172 TI - Exudate variation in the rabbit gastrointestinal tract: a scanning electron microscope study. AB - The mucosal exudate from the gastrointestinal tract of six adult female New Zealand rabbits was studied using scanning electron microscopy and without any attempt being made to clean the luminal surface before screening. The exudate consisted of mucus, debris and bacteria. Qualitative assessment showed that the nature and distribution of exudate varied along the length of the gastrointestinal tract from the oesophagus to the anal canal, with little variation from animal to animal. Bacterial counts for rod-shaped bacteria were carried out on areas randomly selected from the upper, middle and lower oesophagus and the oesophageal-cardiac junction. The degree of bacterial colonisation was found to decrease along the length of the oesophagus from upper to lower parts, but it was increased at the oesophageal-cardiac junction. This assessment was not undertaken in the other regions of the gastrointestinal tract as the mucosal surface areas could not be easily measured owing to their undulating nature. The study indicates the variability of the mucosal exudate, which should be recognised as part of the true interface between ingested food and the cell surface along the gastrointestinal tract. PMID- 2254173 TI - The innervation of the middle ear muscles of the rat. AB - The innervation of the tensor tympani muscle and the stapedius muscle in the rat was studied. This was done by acetylcholinesterase in toto staining of the tympanic bullae and of muscles dissected separately, acetylcholinesterase staining of serial cross-sections of the muscles, silver impregnation of serial sections of complete tympanic bullae, serial semithin sections stained according to Laczko & Levai and electron microscopy of both muscles. The gross innervation of the muscles and the relation to other nerves in the bulla are described. It is shown that both muscles are innervated by very thin nerve fibres which form a well-organised elaborate network in the muscles, with very short branches that connect with motor endplates. Electron microscopically there are indications that the endplates in the stapedius muscle seem to enable faster activation of the muscle fibres than those of tensor tympani muscle. No morphological evidence for any sensory innervation of the muscles could be detected in the muscles themselves, in the connective tissue related to the muscles, or in the contents of the bulla tympanica. It is postulated that the afferent input of the acoustic middle ear muscle reflex is sound alone and that sensory information from the muscles themselves or from other structures in the tympanic bulla do not contribute to the reflex. PMID- 2254174 TI - Spermatic cord torsion: effects of cyclosporine and prednisone on fertility and the contralateral testis in the rat. AB - Unilateral spermatic cord torsion results in contralateral degeneration and reduced fertility in the prepubertal male rat. This study was conducted to investigate the use of immunosuppression with cyclosporine and prednisone to prevent these untoward effects. Thirty-five-day-old male rats were subjected to 720 degrees unilateral spermatic cord torsion of 9 hours duration. At the time of detorsion, animals were given a subcutaneous injection of i) cyclosporine, ii) prednisone, or iii) cyclosporine combined with prednisone. Control groups included: i) animals undergoing orchiectomy of the ipsilateral testis following the torsion period, ii) hemicastration in the absence of torsion and iii) sham surgery. Orchiectomy at the end of the torsion period prevented the torsion induced reduction of fertility, contralateral seminiferous tubule diameter and testis weight. Treatment with cyclosporine combined with prednisone significantly increased these parameters above detorsion alone. These data indicate that short term immunosuppression with cyclosporine alone or in combination with prednisone limits the adverse effects of unilateral spermatic cord torsion as does removal of the damaged organ at the end of the torsion period. PMID- 2254175 TI - Fluid movement in the lumen of the rat epididymis: effect of vasectomy and subsequent vasovasostomy. AB - Intraluminal fluid movement rate was measured in four regions of the rat epididymis. The fastest flow occurred in the proximal caput epididymis (18.5 +/- 3.7 mm/hour) and the slowest in the distal cauda (2.5 +/- 0.5 mm/hour). Vasectomy significantly reduced caput fluid flow rates unless a sperm granuloma was present at the vasectomy site. Thirty days after vasovasostomy, caput fluid movement remained reduced in animals unless a granuloma was present. Failures of this or other aspects of epididymal biology to return to normal after vasovasostomy could play a role in the frequent infertility which persists after the operation. PMID- 2254176 TI - Changing relationships between testis size, Sertoli cell number and spermatogenesis in Sprague-Dawley rats. AB - Relationships between several reproductive characteristics were investigated in 25 Sprague-Dawley rats aged 60, 150, and 240 days (n = 75). Daily sperm production correlated with body weight (r = 0.63), paired testes weight (r = 0.68), testes weight as a percentage of body weight (r = -0.50), the number of spermatids supported per Sertoli cell (r = 0.51) and the number of Sertoli cells per gram (r = 0.89) or per testis (r = 0.95) among rats pooled across age groups. In general, the number and magnitude of significant coefficients of correlation were decreased when calculated within age groups. The latter often appeared to reflect a statistical consequence of relative homogeneity among rats rather than the absence of a biological relationship. However, the total number of Sertoli cells per testis correlated with daily sperm production within age groups, and could account for 85 to 94% of the variability in sperm production at 150 and 240 days, respectively. PMID- 2254177 TI - Acute and chronic effects of cisplatinum upon testicular function in the rat. AB - One of the side effects of cisplatinum-based chemotherapy is the impairment of spermatogenic function. In order to understand the mechanisms responsible for this side effect, the present study examined the short- and long-term effects of five daily injections of 2 mg/kg cisplatinum upon the functional normality of Leydig cells and Sertoli cells in intact adult rats, and their relationship with the status of spermatogenesis. Results of the present study demonstrate that cisplatinum treatment resulted in a progressive but reversible loss of germ cells from the seminiferous epithelium. Although testicular testosterone contents reduced transiently after the adminisration of cisplatinum, these testosterone levels are otherwise sufficient to support complete spermatogenesis. Thus, the cisplatinum-induced germinal regression cannot be accounted for by hypoandrogenism. The testicular ABP contents of the drug-treated rats remained unchanged during the treatment period, decreased transiently 30 days after the treatment, and returned to normal 120 days after treatment. A decrease in epididymal ABP content was also noted 10 and 30 days after the drug treatment. These observations suggest that Sertoli cell functions were affected by cisplatinum treatment. The effects of cisplatinum upon Sertoli cells were further demonstrated by the dose-dependent suppression of the production of ABP, lactate, and estradiol in cultured Sertoli cells. In addition, cisplatinum administration resulted in a reversible decrease in pituitary weights and an irreversible decrease in seminal vesicle weights. These results further demonstrate the toxic effects of cisplatinum upon various aspects of the male reproductive system. PMID- 2254178 TI - Relationship between morphology and motion characteristics of human spermatozoa in semen and in the swim-up sperm fractions. AB - In this study, the authors evaluated the morphology pattern and motion characteristics of human spermatozoa before and after swim-up separation. Samples were divided into two, morphologically different groups according to the percentage of normal sperm forms assessed by the strict criteria of the Norfolk laboratory: "good"(G) and "poor" (P) prognosis patterns. The percentages of normal forms, slightly abnormal forms, and severe head defects were significantly different in the two groups. Motile characteristics were analyzed by a computerized semen analyzer with constant parameter settings. Before swim-up there were no significant differences in semen volume, percentage of neck and tail defects, concentration, or percentage of motility and linearity, but the mean velocity was higher in group G. After swim-up the percentage of motility, total number of motile cells, and recovery rate were higher for group G, and the incidence of severe head defects correlated negatively with the percentage of cells with a velocity of greater than 80 microns/sec. The results suggest that patients with a high incidence of sperm head defects have impaired original velocity, and swim-up selects for velocity as well as normal forms and motility. Although motility and velocity improved substantially after swim-up, the recovery rate and percentage of motility were significantly lower in the P group. PMID- 2254179 TI - A comparison of two computer-automated semen analysis instruments for the evaluation of sperm motion characteristics in the stallion. AB - Two commercially available computer-automate semen analysis instruments (CellSoft Automated Semen Analyzer and HTM-2000 Motion Analyzer) were compared for their ability to report similar results based on the analysis of pre-recorded video tapes of extended, motile stallion semen. The determinations of the percentage of motile cells by these instruments were more similar than the comparisons between subjective estimates and either instrument. However, mean values obtained from the same sample may still differ by as much as 30 percentage units between instruments. Instruments varied with regard to the determinations of mean sperm curvilinear velocity and sperm concentration, but mean sperm linearity determinations were similar between the instruments. We concluded that the determinations of sperm motion characteristics by subjective estimation, CellSoft Automated Semen Analyzer, and HTM-2000 Motility Analyzer are often dissimilar, making direct comparisons of results difficult. PMID- 2254180 TI - Participation of human epididymal sperm coating antigens in fertilization. AB - A polyclonal antiserum directed against human sperm coating proteins of epididymal origin (anti-KCl) was tested for its ability to alter sperm function. Spermatozoa from normal ejaculates were selected by swim-up separation and capacitated by overnight incubation at room temperature. Exposure of these cells to anti-KCl (0.39 mg protein/ml), prior to their use in the hamster ova penetration test, reduced the penetration of denuded oocytes by 65% (P less than 0.005). Significant inhibitions of lesser magnitude were observed at lower serum concentrations (to 0.098 mg/ml). In an effort to understand the mechanism of this inhibition, other sperm function parameters thought to be related to oocyte penetration were studied. The inhibitory effect was exerted without noticeable changes in sperm motility (determined by the percentage of motile cells and their linear velocity), and in the absence of major sperm agglutination. Anti-KCl did not inhibit the occurrence of spontaneous or induced (by human follicular fluid) acrosome reaction in capacitated spermatozoa. In contrast, exposure to anti-KCl reduced the ability of capacitated spermatozoa to bind tightly to the hamster oolemma. None of these effects were elicited by a control preparation obtained from pre-immune rabbit sera. Exposure of zona-free oocytes to the antiserum did not alter their penetrability by normal sperm. These results suggest that the antigens recognized by anti-KCl participate in some specific step of the sperm ovum interaction. PMID- 2254181 TI - Frederick Francis McKenzie, 1900-1986: a brief biography. PMID- 2254182 TI - Effect of prenatal trenbolone acetate treatment on lamb performance and carcass characteristics. AB - Forty-three pregnant Dorset and Dorset crossbred ewes were assigned randomly to a control group or implanted with either 300 mg trenbolone acetate (Low TBA) or 1,200 mg trenbolone acetate (High TBA) between d 40 and 60 of gestation. Adjusted weaning weights for ewe lambs were 23.3% less (P less than .10) with vs without TBA treatments. Postweaning ADG of ewe lambs was lower (P less than .05) but ADG of ram lambs was greater (P less than .05) for high TBA vs low TBA. Ewe lambs receiving high TBA had 19% less (P less than .05) gain per unit of feed than those receiving low TBA. Days on test for ewe lambs was greater (P less than .05) due to TBA treatment and for high TBA vs low TBA. Days on test for ram lambs was decreased (P less than .05) due to high TBA compared to low TBA. Subcutaneous fat over the ribeye and lower rib were greater (P less than .05) for high-TBA ewe lambs vs low-TBA ewe lambs. Percentage kidney and pelvic fat of ewe lambs was lower (P less than .05) due to TBA treatments. Ribeye area per unit of carcass weight was lower (P less than .05) in high-TBA ewe lambs vs low-TBA ewe lambs. Yield grade of ewe lambs was lower (P less than .05) for low TBA vs high TBA. Prenatal trenbolone acetate treatment of ewe lambs did not improve their subsequent postnatal growth performance and carcass traits. In addition, TBA implantation of the pregnant ewe produced dystocia and less milk production, as evidenced by the need for more lambs to be grafted. PMID- 2254183 TI - Effects of feeding restricted energy and elevated calcium and phosphorus during growth on gait characteristics of culled sows and those surviving three parities. AB - Crossbred gilts (n = 288) were weaned at 4 to 5 wk of age and retained through three parities. They were used to determine the effects of feeding restricted energy (ad libitum vs 75% ad libitum) and elevated calcium-phosphorus levels (100 vs 150% of the dietary percentage suggested by NRC, 1979) from weaning to 100 kg of body weight on subsequent sow gait characteristics obtained from 16-mm motion pictures. After 100 kg, all females were fed and managed similarly throughout breeding, gestation and lactation. At 50 and 100 kg body weight and 21 d after weaning, females were filmed from the side and rear as they walked on a treadmill (traveling at the rate of .90 cm/s with zero slope) using two 16-mm Arriflex cameras. Objective measurements were taken from the film by projecting it on a reverse screen. Visual appraisal of structural soundness were scored subjectively for each female at each time period. The front foot pastern angle was correlated positively with structural soundness scores, suggesting that sows with smaller angles (more sloping) were given more desirable soundness scores. Early dietary energy and Ca-P levels did not influence number of sows completing three parities or culled for various reasons, front and hind pastern angles, the angles at the hock and carpal joint or rear view measurements, but sows fed ad libitum to 100 kg had a larger frame size even after three parities. Sows that survived three parities tended to have larger body capacity (girth diameter and width across hams) and smaller front and bind pastern angles and angles of the carpal joint and hock at maximum flex than did culled sows. Structural soundness scores did not differ between culled and surviving sows. PMID- 2254184 TI - Influence of alumni careers and students' educational pathways on animal science undergraduate teaching programs. AB - In an attempt to aid the planning of courses and curricula in animal science, a survey instrument concerning careers, opinions and suggestions regarding education received was sent to 1,398 alumni who had graduated during the years 1956 to 1987. Longitudinal studies of 1972-82 entering animal science students, and a telephone survey of students who entered as freshmen in 1985-86, provided information concerning student profiles and educational interests. Fifty-two percent of alumni were women, 61% had obtained advanced degrees, about 50% were veterinarians, laboratory or medical scientists, business owners or managers, only 8% were ranch owners or managers, and the rest were engaged in a multiplicity of careers. Undergraduate experiences judged most important by alumni were obtaining academic skills, followed by advanced biology courses, animal science courses, work experience and developing the ability to continue learning. Alumni suggestions for change gave priority to offering more practical subject matter and business and economics in the animal science program, followed by more general education, research, science and theory, or no change. Approximately 30% of entering freshmen students graduated in the animal science major. Fifteen percent expressed interest in livestock, 23% in horses, 29% in companion animals, and the rest in a wide variety of animals. PMID- 2254185 TI - Effect of rotating monensin plus tylosin and lasalocid on performance, ruminal fermentation, and site and extent of digestion in feedlot cattle. AB - Two trials were conducted to evaluate the effects of ionophore rotation programs on performance and digestion by feedlot cattle. A 90% concentrate diet was fed with treatments of no ionophore (C), 33 mg lasalocid/kg diet daily (L), 29 mg monensin plus 11 mg tylosin/kg diet daily (MT), and daily (D) and weekly (W) rotation of L and MT. In Trial 1, feedlot performance of 200 crossbred steers (average initial BW 296 kg) was evaluated during a 133-d period. In Trial 2, four crossbred steers (average initial BW 376 kg) fitted with ruminal, duodenal and ileal cannulas were used in a 4 x 4 Latin square design to evaluate treatment effects (excluding W) on ruminal fermentation and site and extent of digestion. In Trial 1, daily rotation of L and MT improved (P less than .10) feed:gain ratio compared with other treatment groups, but daily feed intake did not differ (P greater than .10) among treatments. Daily gain was greater (P less than .10) for steers fed D than for those fed C or MT, but not different from that of steers fed L or W. Carcass measurements did not differ (P greater than .10) among treatments. In Trial 2, ruminal molar proportions of butyrate and valerate were decreased (P less than .07) by MT and D compared with C and L. Proportions of other VFA, ammonia concentrations and ruminal pH did not differ among treatments. Ionophore treatments did not affect site or extent of digestion of OM, starch or N; no differences among treatments were observed for efficiency of microbial protein synthesis. Although daily rotation of L and MT improved performance of growing-finishing feedlot steers, this improvement was not attributable to alterations in ruminal fermentation, or in site or extent of nutrient digestion. PMID- 2254186 TI - Feedlot performance of beef heifers implanted with Synovex-H: effect of melengestrol acetate, ovariectomy or active immunization against GnRH. AB - The effects on anabolic steroid implantation on feedlot performance and carcass composition and quality were examined in control (CNTRL), ovariectomized (OVX) or melengestrol acetate-fed (MGA) beef heifers or heifers actively immunized against GnRH (Anti-GnRH). Heifers (n = 112) were assigned randomly to a 2 x 4 factorial experiment. The two classes were made up of heifers not implanted and those implanted with Synovex-H. The four treatments were 1) CNTRL, 2) MGA, 3) OVX and 4) Anti-GnRH. Heifers were housed in individual pens and fed a high-energy diet for the 4-mo study. Synovex-H increased final live weight (P less than .005), carcass weight (P less than .005), ADG (P less than .0001) and feed efficiency (P less than .005) but did not alter carcass quality and yield grade (P greater than .05). Synovex-H increased deposition of protein (P less than .0001) and reduced deposition of fat (P less than .0001). Oral administration of MGA had no significant effect on feedlot performance or carcass quality. For heifers not implanted, active immunization against GnRH, but not ovariectomy, depressed ADG (P less than .05) and increased fat deposition (P less than .05) while reducing protein deposition (P less than .05). These effects of active immunization were reversed by concurrent administration of Synovex-H. Feedlot performance and carcass composition of heifers were improved by administration of anabolic steroids. When heifers were housed singly, neither ovariectomy, active immunization against GnRH nor oral administration of MGA improved feedlot performance of heifers implanted with Synovex-H. PMID- 2254187 TI - Effects of feeding growing cattle high-concentrate diets at a restricted intake on feedlot performance. AB - Three trials were conducted to compare effects of restricted intake of high concentrate diets vs ad libitum intake of corn silage diets during the growing phase on feedlot cattle performance. In Trial 1, 120 steers (initial BW, 246 kg) were fed 1) a corn silage-based diet ad libitum, 2) a high-moisture corn-corn silage-based diet with intake restricted to a level 20% less than that of the corn silage diet or 3) a high-moisture corn-based diet with intake restricted to a level 30% less than that of the corn silage diet. Steers fed the 20% restricted corn-corn silage-based diet tended (P = .07) to gain slower than those fed the corn silage or 30% restricted high-concentrate diet. Feed efficiency and diet digestibility were greatest for steers fed the 30% restricted-intake, high concentrate diet (P less than .01). Performance of steers during the subsequent 118-d finishing period was not affected (P greater than .65) by source of energy during the growing period. In Trial 2, ADG of steers fed the 30% intake restricted, high-concentrate diet was lower (P less than .01) than that of steers with ad libitum access to corn silage. During the 84-d growing period, steers fed supplemental blood meal had 8.3% greater gains and a 6% greater efficiency of feed use than those fed supplemental soybean meal (P less than .01). Monensin did not affect (P = .82) performance of steers fed 30% restricted-intake diets. During the 76-d finishing period, gains and feed conversion were improved (P less than .01) for steers fed the restricted-intake diet in the growing period compared with those given ad libitum access to corn silage. During the growing period in Trial 3, ADG of steers restricted-fed an all-concentrate diet were slightly greater (P less than .10) than ADG of those given ad libitum access to corn silage. Gains did not differ (P = .37) during the subsequent finishing period when steers were switched to 85 or 100% concentrate diets. We concluded that intake of all concentrate diets can be restricted to achieve gains equal to those of steers given ad libitum access to corn silage-based diets without detrimental effects on finishing performance. PMID- 2254188 TI - Efficiency of weight gain of serial slaughtered bulls of a five-breed diallel. AB - Weight and feed consumption of 197 bulls were recorded monthly in a serial slaughter experiment continuing over a period of 24 mo. The bulls were produced in a modified five-breed diallel of the Angus, Brahman, Hereford, Holstein and Jersey breeds. Our objective was to estimate efficiency of feed conversion for weight gain for each breed and cross. The model included average weight gain per day (ADG) as a dependent variable; independent variables included breed-type, season, month within season, average feed intake per day (ADI), initial weight, weight to the .75 power, breed x ADI and season x ADI effects. The sum of the partial regression coefficients of ADG on ADI and on breed x ADI adjusted for season, month within season, initial weight, weight to the .75 power and season x ADI was interpreted to be an estimate of intrinsic or net efficiency of ADG. There were no significant differences among the various breed-types in intrinsic efficiency of ADG. Average heterosis for intrinsic efficiency of feed conversion was not significant. None of the contrasts among breed-types was significant for intrinsic efficiency of ADG (British vs dairy, 1.1 +/- 12.3 g/d; Brahman-dairy crosses vs British-dairy crosses, 32.7 +/- 12.9 g/d; British-Brahman crosses vs British-dairy crosses, 13.9 +/- 12.4 g/d; British-Brahman crosses vs straightbred British 3.2 +/- 14.8 g/d). PMID- 2254189 TI - Measurements at calving for straightbred and crossbred cows of diverse types. AB - Reproductive and calving records of 611 cows from F1 and F2 generations from a diallel mating system with Angus, Brahman, Hereford, Holstein and Jersey were examined. The inter se matings were by artificial insemination, and each cow had three or four parturitions. Dependent variables included weight, hip weight at first calving, age at first calving, gestation length and calving interval. Brahmans were the heaviest, tallest and oldest purebred at first calving. Crossbred Brahman females tended to be older than other crosses at first calving. Purebred Brahmans and one-half Brahman crosses also had the longest gestation lengths and calving intervals. First-gestation (F1) crossbred cows were 18 kg heavier (P less than .05), 2.0 cm taller (P less than .01) and 35 d younger (P less than .05) at first calving than contemporary straightbreds. Average maternal heterosis for height at calving was significant (1.4 cm; P less than .05); however, estimates of specific and average maternal heterosis for measurements taken at first calving were generally nonsignificant. Estimates of specific and average individual and maternal heterosis were generally small and nonsignificant for gestation length and calving interval. PMID- 2254190 TI - Body composition and tissue distribution from birth to 14 months for three biological types of beef heifers. AB - Thirty-four heifers were sampled randomly from each of the Hereford (He), Charolais (Ch) and Simmental (Si) herds at the U.S. Meat Animal Research Center at 2 d to 14 mo of age to examine body chemical composition and tissue distribution. Six heifers per breed were slaughtered after calorimetry at 2 d, 3 mo, 7 mo, 10 mo and 14 mo of age, and four others at 8 mo, to measure weight of empty body (EBW), water, fat, ash and protein as residual, in four fractions: carcass (CAR), head, hide and shanks (HHS), gastrointestinal tract plus internal fat (GIF) and visceral organs plus blood (VOB). Fasted live weight from birth to 14 mo increased from 39 to 414 kg for Ch, 38 to 385 kg for Si and 33 to 356 kg for He. Corresponding mean composition of EBW increased from 58 to 67% CAR and from 7 to 13% GIF but declined from 26 to 15% HHS and from 9 to 6% VOB. The water content of EBW declined from 73 to 51%, protein from 20 to 18% and ash from 4.3 to 3.5%, whereas fat increased from 3 to 28% and protein content of fat-free OM increased from 22% to 26%. Composition of CAR was similar to EBW but fat content increased more with age in GIF, less in HHS and least in VOB. Distribution of fat free tissue changed from 58 to 66% in CAR, 26 to 18% in HHS, 7 to 8% in GIF and 9 to 8% in VOB. The EBW of Ch contained more CAR but less HHS than EBW of Si and HE. The EBW of Si and Ch contained more water and protein and less FAT than EBW of HE. The fatter He had proportionately less of their fat-free tissue in CAR (63%) and more in HHS (21%) and GIF (9%) than the Ch (66, 19, and 8%), with Si (64, 20 and 8%) intermediate. These age and breed differences in composition and tissue distribution may explain some of the variation in maintenance requirements. PMID- 2254191 TI - Estimation of additive genetic variance when base populations are selected. AB - A population of size 40 was simulated 1,000 times for 10 generations. Five out of twenty males were selected each generation, and each male was mated to four females to have two progeny. The additive genetic variance (sigma 2a) before selection was 10, and the initial heritability was .5. Due to covariances among animals, inbreeding and gametic disequilibrium, the genetic variance was reduced to 6.72 after 10 generations of selection. Reduction of variance was lower in another population simulated with size 400 and 10% of the males selected. Restricted Maximum Likelihood was used to estimate sigma 2a using an animal model. The estimate of sigma 2a was empirically unbiased when all data and all relationships were used. Omitting data from selected ancestors caused biased estimates of sigma 2a due to not accounting for all gametic disequilibrium. Including additional relationships between assumed base animals adjusted for inbreeding and for covariances. Bias from gametic disequilibrium decreased slightly with the use of more relationship information, and it was smaller in the small population and(or) when selection had been practiced for just a few generations. PMID- 2254192 TI - Twinning in cattle: III. Effects of twinning on dystocia, reproductive traits, calf survival, calf growth and cow productivity. AB - An evaluation of natural twinning in beef cattle revealed that cows birthing twins had shorter (P less than .01) gestation lengths, more (P less than .01) retained placentas, more (P less than .01) dystocia, more (P less than .01) days to estrus, lower (P less than .01) conception rates and more (P less than .01) days to pregnancy than cows birthing singles. Days to estrus, conception rate and days to pregnancy were not affected by number of calves reared (1 vs 2) in cows birthing twins. Survival at birth was greater (P less than .01) for single- than for twin-born calves, but twins and singles did not differ (P greater than .05) in postnatal survival. When dystocia was experienced, calf survival at birth was 95% vs 73% for singles vs twins compared with 99% vs 92% when no dystocia was experienced. Calves born twins were lighter (P less than .01) at birth, 100 d and 200 d, but twins and singles did not differ in postweaning gains. Total calf weights at 100 d per cow calving were 12% greater (P less than .01) in cows birthing twins vs singles when twin calves reared by foster dams were excluded. The potential increase in cow productivity for total calf weight at 100 d is 40% if calf survival rates of twins with dystocia relative to survival rates of twins without dystocia were comparable to survival rates of singles with and without dystocia, and if cows birthing twins were fed and managed to obtain conception rates equal to those of cows birthing singles. Identification of cows gestating twins to provide for their higher prepartum nutritive requirements and calving assistance at parturition is necessary to make twinning in cattle an economically viable technology. PMID- 2254193 TI - Cold housing effects on growth and nutrient demand of young horses. AB - Housing temperature effects on growth, feed utilization and feed digestion of 12, 7-mo-old Standardbred colts were evaluated for 22 wk beginning in late November. Colts were assigned to one of two treatments: housed in a barn heated at 10 degrees C (warm) or housed in a barn with no external heat supply (cold). All horses were allowed outdoors for 4 h daily. Mean temperatures of the warm and cold barn from November to April were 10.9 +/- .66 and -5.2 +/- 1.72 degrees C, respectively. Hair coat weight of cold-housed colts was 1.4- to twofold (P less than .05) that of warm-housed colts from December through April but declined for both groups from fall to spring. All colts were fed a pelleted diet to meet National Research Council (1989) energy guidelines for moderate gain (.65 kg/d). Warm-housed colts gained weight 29% more rapidly (P less than .01) than cold housed colts (.67 vs .52 kg/d). Skeletal growth, measured by cannon bone circumference, wither and croup height, was not affected by housing temperature. Nutrient digestion by both groups of colts was compared to that of mature, warm housed ponies. Ponies had longer (P less than .05) digestive tract retention times and higher digestibilities for every nutrient than the young horses did. Although retention times by all colts were similar, cold-housed colts digested more ADF and less phosphorus (P) than did warm-housed colts (P less than .05). Over time, digestibilities of DM, NDF and P declined (P less than .05) for colts but not for ponies. Maintenance energy needs were estimated at 34.6 kcal/kg BW for cold-housed colts vs 26.3 kcal/kg BW for warm-housed colts. Young horses need 1.3% more maintenance energy per Celsius degree decrease in temperature below 0 degree C. To sustain a constant moderate gain, daily DE intake needs to be increased .7% per Celsius degree decrease in ambient temperature below 0 degree C. PMID- 2254194 TI - Characterizing rumination patterns of dairy cows using spectral analysis. AB - Spectral analysis techniques were used to characterize the cyclical variation in rumination behavior of cows. Four Holstein cows were fed twice daily a diet of 60% high-moisture shelled corn-based concentrate, 15% first-cut alfalfa-grass hay and 25% second-cut alfalfa silage. The number of minutes that each cow spent ruminating was determined for 15-min intervals during six consecutive days. Rumination data then were characterized using Fourier harmonic analysis to decompose the total sum of squares into 288 orthogonal components due to different rumination wavelengths. Rumination patterns for all cows consisted mainly of wavelengths that were harmonics of a 24-h cycle, indicating a circadian pattern of rumination. Differences in rumination patterns between cows occurred mainly at wavelengths of less than 2 h. Rumination patterns of two of the four cows were more complex, and consisted of high-frequency, non-24-h harmonic wavelengths in addition to the circadian pattern. Spectral analysis can be used to identify the component cycles of rumination patterns of individual animals, which can then be used to determine the effects of dietary or other manipulations on rumination behavior. PMID- 2254195 TI - In vitro muscle cell proliferation and protein turnover as affected by serum from pigs fed antimicrobials. AB - The effect of antimicrobial supplementation of pigs on the capacity of their sera to influence proliferation and protein turnover in cultured muscle cells was evaluated. Mitogenic activity of sera increased when pigs were fed ASP250 (P less than .005) or carbadox (P less than .001), whereas the mitogenic activity of serum from pigs receiving the basal diet remained unchanged (P = .5). Additionally, sera from ASP250-fed pigs significantly decreased (P less than .001) total cellular protein degradation compared with sera obtained from the same pigs prior to supplementation. Neither ASP250 nor carbadox stimulated proliferation of myogenic cells when added to the culture media. Inclusion of ASP250 in swine diets altered the composition of their sera in a way that stimulated muscle cell proliferation and reduced the rate of protein degradation in cultured myogenic cells. Likewise, the inclusion of carbadox in swine diets increased the ability of their sera to stimulate cultured muscle cell proliferation. PMID- 2254196 TI - Growth hormone release after N-methyl-D,L-aspartate in sheep: dose response and effect of an opioid antagonist. AB - The objectives of our experiments were 1) to determine the effect of N-methyl-D,L aspartate (NMA), an agonist of the neuroexcitatory amino acids aspartate and glutamate, on growth hormone (GH) release in ovariectomized ewes, and 2) to determine the effect of naloxone, an opioid antagonist, on the GH response to NMA. Jugular blood was collected via venipuncture at 12-min intervals for 2 h before and 2 h after i.v. injection of NMA. In Exp. 1, ewes received either 0, 6, 12 or 24 mg NMA/kg BW dissolved in .9% saline solution (n = 4 per treatment). Growth hormone concentrations were similar (P greater than .1) between groups prior to injection (9.8 +/- .7 ng/ml; mean +/- SEM) and were unaffected (P greater than .1) by saline treatment. In contrast, 6, 12 or 24 mg NMA/kg BW increased mean GH concentration by 210% (P less than .04), 273% (P less than .02) and 234% (P less than .02), respectively. In Exp. 2, ewes received NMA (6 mg/kg BW) 5 min after either saline (n = 4) or naloxone (1 mg/kg BW; n = 4) pretreatment. Serum GH concentrations averaged 7.0 +/- 1.1 ng/ml before pretreatment and increased similarly (238%; P greater than .1) in both groups following NMA. In summary, NMA increased GH concentrations in ovariectomized ewes by some mechanism that does not involve opioid receptors that are antagonized by naloxone. PMID- 2254197 TI - The effect of human growth hormone-releasing factor or porcine somatotropin on serum hormones and metabolites, growth performance and carcass traits in swine. AB - Forty barrows (77.9 +/- 5.5 kg BW) were allotted to one of five treatment groups to examine the effects of various doses of human growth hormone-releasing factor (1-44)NH2 (hGRF) or porcine somatotropin (pST) administered twice daily on serum hormones and metabolites, performance and carcass traits. Barrows were injected s.c. with either a placebo, 10 micrograms hGRF.kg BW-1.12 h-1, 20 micrograms hGRF.kg BW-1.12 h-1, 20 micrograms pST.kg BW-1.12 h-1 or 40 micrograms pST.kg BW 1.12 h-1 for a 36-d growth trial. Blood samples were collected from 13 barrows at intervals for 360 min after injection on d 21. Compared with the placebo, 10 micrograms hGRF.kg-1.12 h-1 increased (P less than .01) serum pST and insulin and decreased (P less than .001) urea N. Injecting 20 micrograms hGRF/kg.12 h-1 elevated (P less than .001) serum pST, insulin and insulin-like growth factor-I (IGF-I) but lowered (P less than .001) urea N. Exogenous pST increased (P less than .001) serum pST, insulin, IGF-I and glucose but decreased (P less than .001) urea N. Growth rate tended to increase, and feed intake and feed/gain decreased, in a dose-related manner in response to hGRF. Also, pigs receiving 10 or 20 micrograms hGRF.kg-1.12 h-1 had reduced (P less than .1) backfat and increased (P less than .1) loineye area and percentage lean in the ham compared with pigs receiving the placebo. At equal doses, pST elicited more dramatic improvements in performance and carcass criteria than did hGRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254198 TI - Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs. AB - Sixty-six intact male pigs were used to investigate the relationships between exogenous porcine growth (pGH) administration (0, excipient-treated, and .09 mg recombinant pGH.kg-1.d-1) and dietary protein content (8.3, 11.4, 14.5, 17.6, 20.7 and 23.8%) on protein and lipid accretion rates over the live weight range of 30 to 60 kg. Feed intakes were restricted (1.84 kg.pig-1.d-1) and pGH was administered daily by i.m. injection. Rate of protein deposition increased with increasing dietary protein up to 17.6 and 20.7%, respectively, for control and pGH-treated pigs; both growth and protein deposition were enhanced by pGH on the four higher protein diets but remained unaffected by pGH administration to pigs given the two lowest protein diets. Plasma IGF-I concentration was elevated by pGH administration in pigs given the four higher protein diets but unaffected by pGH with the two lowest protein diets. Rate of fat deposition was depressed on all dietary protein treatments by pGH administration; carcass fat content of control and pGH-treated pigs declined with each increase in dietary protein up to 17.6 and 23.8%, respectively. The results demonstrate that pGH acts independently on protein and lipid metabolism. PMID- 2254199 TI - Effects of ethanol extraction and duration of heat treatment of soybean flakes on the utilization of soybean protein by growing rats and pigs. AB - Three experiments were conducted to determine the effects of ethanol extraction and duration of heat treatment of soybean flakes on the utilization of soybean protein by growing rats and pigs. In the first experiment, the treatments were no extraction or extraction with a 55% ethanol-water mixture (v/v), and heat treatments of 0, 5, 10, 20 and 40 min in an autoclave. Ethanol extraction improved rate (P less than .002) and efficiency of gain (P less than .001) of rats. As heat treatment was increased from 0 to 20 min, rate of gain increased, but it decreased again as heating time was increased from 20 to 40 min (P less than .03). In Exp. 2 and 3, 45 pigs were used in a growth assay and 54 were used in a N balance experiment to determine the effects of ethanol extraction on under , intermediate- and over-processed soybean flakes (i.e., 5, 20 and 60 min of autoclaving). The heat treatments were applied either without, before or after extraction with ethanol. Responses in rate and efficiency of gain to ethanol extraction were greater for soybean flakes heated for either 5 or 60 min than for the soybean flakes heated for 20 min. When pooled across heat treatment, pigs fed the soybean flakes heated before or after extraction with ethanol gained faster (P less than .001), had greater gain:feed (P less than .001) and lower plasma urea concentrations (P less than .002) than pigs fed soybean flakes heated without extraction. Feeding soybean flakes heated and extracted with ethanol also resulted in greater apparent N retention (P less than .003), apparent N digestibility (P less than .001) and apparent biological value (P less than .03) than soybean flakes that were heated without extraction. Ethanol extraction improved the protein quality of soybean flakes, especially when the flakes were under- or overprocessed with heat. PMID- 2254200 TI - Effects of ethanol extraction and heat treatment of soybean flakes on function and morphology of pig intestine. AB - Digesta and tissue samples were collected from the intestinal tracts of 27 pigs to determine the relationship between intestinal morphology and the utilization of nutrients from soybean flakes. Soybean flake treatments were under-, intermediate- and over-processed (i.e., 5, 20 and 60 min of autoclaving) either without extraction or with heating before or after extraction with a 55% ethanol water mixture. Final BW was greatest (P less than .001) for pigs fed soybean flakes given 20 min of heat treatment. There was a trend (P less than .09) for plasma lysine concentrations to be reduced when the unextracted soybean flakes were over-processed (60 min of heat). Differences in the flow rate of DM and N through the ileum and colon reflected differences in DM and N intake, rather than differences in intestinal function. The soybean flake treatments had no effect (P greater than .08) on pH of the contents of the stomach, duodenum, ileum or colon. The ethanol extraction process increased (P less than .001) N digestibility of the soybean flakes, especially when the soybean flakes were underprocessed (interaction, P less than .02). Villus size (area, height and perimeter length) tended to be greater in pigs fed the soybean flakes heated after extraction and(or) exposed to the intermediate level of heat treatment. Indicators of villus shape (villus area/villus height) and proliferative activity (crypt depth and villus height/crypt depth) were not affected by soybean flake treatment (P greater than .08). Ethanol extraction and heat treatment affected the utilization of nutrients from soybean flakes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254201 TI - Effect of vitamin E, phosphorus and sorbitol on growth performance and serum and tissue cholesterol concentrations in the pig. AB - A total of 180 crossbred, weanling pigs were assigned to five dietary treatment groups: 1) a basal corn-soybean meal diet formulated to current NRC recommendations, 2) basal + monosodium phosphate (2 x NRC P recommendations; P), 3) basal + alpha-tocopheryl acetate (220 IU/kg; E), 4) basal + sorbitol (1% of the diet; S) and 5) basal + PES. Dietary treatments were continued until market weight (104 kg). Blood samples were obtained at 3-wk intervals for analysis of serum alpha-tocopherol, P and total cholesterol. Liver and muscle (semimembranosus) samples were obtained at the end of the starter, grower and finisher phases for determination of total cholesterol concentration. The Ca:P imbalance produced by the high-phosphorus diets (P and PES) increased feed intake during the finisher phase. Dietary treatment did not consistently affect total serum cholesterol at any phase of growth. A transient 21.5% (P less than .05) depression of liver cholesterol concentration was observed in the PES-fed pigs at the end of the starter phase but was not apparent at market weight. A similar trend (nonsignificant) was noted for muscle cholesterol concentration. The present study suggests that the PES diet can decrease tissue cholesterol concentration during the nursery phase, but it remains uncertain whether this transient response is a function of age and(or) diet transition at weaning. Further research is necessary to determine whether this response can be translated to the finishing phase, and thereby reduce carcass cholesterol. PMID- 2254202 TI - Pharmacokinetics of 4-methylimidazole in sheep. AB - The pharmacokinetics of 4-methylimidazole (4MI), a toxin found in ammoniated forage, was studied after i.v. infusion or oral administration of a single dose of 20 mg 4MI/kg BW to sheep. A two-compartment open model was used to describe i.v. infusion data. Oral data were described by a one-compartment open model. A rapid distribution phase (t1/2 alpha = 28 min) was observed after i.v. infusion. The biological half-lives obtained after i.v. infusion (t1/2 beta = 9.72 h) and oral dosing (t1/2 beta = 9.37 h) were similar. The bioavailability of oral 4MI was .69, with a relatively rapid absorption phase (t1/2abs = 1.52 h). The relatively large volume of distribution (61.6 and 65.8 liters for i.v. infusion and oral dosage, respectively) indicates that 4MI is distributed in the extravascular compartment. A dose of 20 mg/kg BW did not cause any apparent ill effects to the animals. PMID- 2254203 TI - Neuroendocrine measurements in steers grazed on endophyte-infected fescue. AB - Dopamine (DA), serotonin (5HT) and selected precursors and metabolites were measured in the anterior pituitary gland, hypothalamus and pineal gland, along with serum prolactin (PRL) and average daily gains (ADG), in steers (n = 6/group) grazing endophyte (Acremonium coenophialum)-infected and noninfected fescue (Festuca arundinacea Schreb). Paddocks (two/treatment) were designated 100F and 0F (100 and 0% infection, respectively). After 6 wk, three animals from one of the 100F paddocks were exchanged with three animals from one of the 0F paddocks, yielding 0F, 100F/0F, 0F/100F and 100F groups (n = 3). Compared to 0F steers, 100F steers had reduced serum PRL (9.23 vs 32.55 ng/ml, P less than or equal to .0001) and trial ADG (-.07 vs .28 kg, P less than or equal to .0002) but increased pituitary dihydroxyphenylacetic acid (DOPAC, a major metabolite of DA; 108 vs 59 ng/g, P less than or equal to .02) and 5-hydroxyindoleacetic acid (5HIAA, a major metabolite of 5HT; 265 vs 148 ng/g, P less than or equal to .04). Pituitary 5HIAA was greater in the steers rotated from the 0F to 100F paddocks than in steers maintained on the 0F paddocks (296 vs 148 ng/g, P less than or equal to .04). In addition pineal 5-hydroxytryptophan (5HTP, a precursor of 5HT) was increased (502 vs 280 ng/ml; P less than .08), whereas 5-methoxyindoleacetic acid (MIAA, a major metabolite of 5HIAA) and the 5HT/5HTP ratio were reduced (P less than .07) in 100F vs 0F steers. No differences among the treatment groups were observed in hypothalamic neurotransmitter and metabolite concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254204 TI - Effects of 21-day treatment with melengestrol acetate (MGA) with or without subsequent prostaglandin F2 alpha on synchronization of estrus and fertility in beef cattle. AB - Beef cattle were treated to synchronize estrus using one of three procedures, and effects on subsequent endocrine responses and fertility were studied. Procedures were 1) feeding .5 mg.head-1.d-1 of melengestrol acetate (MGA) for 21 d (M), 2) feeding .5 mg.head-1.d-1 of melengestrol acetate for 21 d followed 14 d later by a single injection of prostaglandin F2 alpha (M + P) and 3) two injections of prostaglandin (PGF) 14 d apart (P). In Exp. 1, 94 beef cows were assigned to be artificially inseminated 12 h after detection of estrus. Procedures for synchronizing estrus did not affect the proportion of cows observed in estrus within 7 d (mean = 70.2%). However, conception rate of cows treated with MGA alone was lower (P less than .01) than that of cows treated with PGF alone (31.8 vs 78.3%). The conception rate of cows in the M + P group was intermediate (57.1%) but greater than that of cows treated with MGA alone (P less than .10). In Exp. 2, 18 heifers were observed for estrus four times daily and bled daily from 1 wk before predicted estrus until second estrus or 35 d post-treatment. Heifers treated with MGA alone maintained lower concentrations of progesterone and higher concentrations of estradiol-17 beta before first estrus than heifers treated with MGA and PGF or PGF alone (P less than .01). Conception rate following insemination was lower after long-term feeding of MGA than after two injections of PGF. Delaying insemination until after a PGF-shortened cycle 14 d after MGA resulted in an intermediate conception rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254205 TI - Effect of dietary energy restriction on metabolic and endocrine responses during the estrous cycle of the suckled beef cow. AB - A replicated trial was conducted with suckled Angus and Polled Hereford cows (110 d postcalving) to determine metabolic and endocrine responses to an energy restricted diet after cows had re-established postpartum estrous cyclicity. Cows were individually fed 26.5 Mcal ME (H) or 15.2 Mcal ME (L) for a 30-d preliminary period and fitted with an indwelling jugular cannula at synchronized estrus. Average daily weight change during the estrous cycle was .60 +/- .25 and -1.37 +/ .30 kg/d for H and L, respectively (P less than .05). Blood concentrations of cortisol, progesterone and LH during the estrous cycle were not affected by diet, nor did diet affect frequency or amplitude of LH pulses (P greater than .05). No dietary differences were observed for daily concentrations of total protein, glucose, nonesterified fatty acids or acetate. Mean blood concentrations of propionate and butyrate were not different between diets; however, L cows had lower concentrations of propionate and butyrate on d 11 of the cycle (P less than .05). Cows fed L had higher concentrations of blood urea nitrogen (P less than .05), but they had lower concentrations of cholesterol (P less than .05) on d 4, 11, 18 and subsequent estrus (E). Insulin was not different on d 4 and 11; however, cows fed L had lower insulin concentrations on d 18 and d E (P less than .05). Dietary energy restriction in these cyclic cows caused no change in endocrine responses. Of metabolic responses measured, only blood urea nitrogen, cholesterol and insulin showed consistent changes. PMID- 2254206 TI - Disappearance and passage of propionic acid from the rumen of the beef steer. AB - Studies were conducted to define steady state pH, propionic acid concentrations and fluid turnover in the rumen of steers fed every 3 h and to determine whether rates of ruminal propionic acid disappearance were linearly related to their in situ production rates. Ruminally fistulated beef steers (326 +/- 11 kg; n = 3) were fed eight times daily a 54% mixed hay: 46% corn-based concentrate diet to meet maintenance energy requirements. Maximal acceptable variations from the mean at steady state conditions of pH, propionic acid concentrations and specific activity, and liquid flow (Cr marker concentrations) were defined as 4%, 20%, 30% and 10%, respectively, across 4 h of observation. In situ production of propionic acid, determined by pulse-continuous infusion of 1-14C-propionic acid, was 142 mmol/h (CV = 8.4%). The ruminal half-life of propionic acid was estimated to be 1.5 h and the liquid flow rate was 3.8 liters/h. Propionic acid production rates subsequently were elevated by continuous intraruminal infusion of buffered propionic acid. Irrespective of production (basal and infusion) rate, approximately 66% disappeared (i.e., presumed absorption) and 34% passed from the rumen to the lower tract in the liquid phase. Ruminal disappearance of propionate was linearly related with its production rate, and propionate concentrations and production rates also were linearly related. Liquid passage was linearly related to production rate, but there was insufficient evidence to conclude that fractional dilution rate or ruminal volume were similarly related. When ruminal production of propionic acid is elevated, the rumen has additional absolute capacity to remove propionate, but the fractional removal appears to be constant. The digestive tract distal to the rumen is likely an important site of propionate absorption in cattle when propionate production is high. PMID- 2254207 TI - Quantity and characteristics of microorganisms associated with ruminal fluid or particles. AB - An experiment was conducted to 1) determine quantity of microbial CP and DM associated with undigested feed particles, 2) quantify the amount of microorganisms removed from ruminally incubated forages and 3) compare forage disappearances (D) corrected for microbial contamination, using diaminopimelic acid (DAPA) ratios obtained from particle-associated or fluid-associated microorganisms. Samples of alfalfa hay, bermudagrass hay and orchardgrass hay placed in dacron bags were incubated via ruminal cannula for 6 and 12 h. Whole ruminal contents (WRC) were sampled at the time of bag removal and partitioned into fluid- and particle-associated microorganisms. Particle-associated microorganisms were further divided into loosely-associated (LA) and firmly associated (FA) microorganisms. Percentage microbial CP and DAPA, quantities of OM, CP (mg) and DAPA (micrograms), microbial contamination and microbial contribution to ruminal contents were not affected by time (P greater than .05). The highest concentrations of CP and DAPA were found in fluid and LA, respectively (P less than .01). The total amount (content) of OM, CP and DAPA were highest in FA and lowest in microbes in the fluid fraction. Firmly associated microorganisms constituted 54.1% of the particle-associated population. Corrected DMD were higher (P less than .01) based on FA than on fluid and LA microbe compositions. Corrected CPD were similar (P greater than .10) between populations except at 6 h, when LA corrected CPD were lower. Theoretically, using FA microorganisms should give the most accurate correction for microbial contamination. However, results indicate that, although the three populations differed in composition, fluid and FA corrected CPD were similar. Corrections based on composition of any of these three populations will yield higher estimates of disappearance compared with uncorrected values. PMID- 2254208 TI - Effects of mastication and microbial contamination on ruminal in situ forage disappearance. AB - In an experiment to determine the effects of mastication and microbial contamination on in situ forage disappearance, samples of masticated (M) or nonmasticated alfalfa hay (AH), orchardgrass hay (OGH) and bermudagrass hay (BGH) were incubated in the rumen of two steers for 6, 12, 24, 48 and 96 h. Using diaminopimelic acid as a marker, microbial DM and CP contamination ranged from 10.3 to 22.3% and 46.3 to 95.3% of residual DM and CP, respectively. Percentage contamination was influenced by both time of incubation and forage treatment (P less than .001). Corrected DM and CP disappearances (DMD and CPD) were higher than apparent disappearances (P less than .001). Maximal NDF and ADF disappearances (NDFD and ADFD) obtained at 96 h were 58.2, 52.4; 62.7, 62.3 and 56.7, 52.6% for AH, OGH and BGH, respectively. Lag times (h) for corrected DMD and CPD were shorter (at least P less than .05) than for apparent disappearances, except for corrected CPD of AH. There were no differences (P greater than .10) in lag time of NDFD or ADFD among forages. Rates of disappearance (%/h) of corrected DMD and CPD were faster (at least P less than .01) than for apparent disappearances. The total quantity of microbial CP (mg CP/g DM) associated with residues varied with time depending on forage type (P less than .001). There was a significant relationship between the quantity of microbial CP contamination and the extent of disappearance. Masticated forages followed trends similar to those of nonmasticated forages, but the effect of mastication was not consistent. Results support the need for microbial correction of in situ forage residues. PMID- 2254209 TI - Efficacy of laidlomycin propionate for increasing rate and efficiency of gain by feedlot cattle. AB - One thousand twenty steers and heifers were used in six feeding trials to examine the influence of laidlomycin propionate on feedlot performance and to determine the most efficacious dietary concentrations of that ionophore. Cattle were fed diets ranging in energy content from 1.08 to 1.49 Mcal NEg/kg of DM. Laidlomycin propionate improved rate of gain and feed conversion in both steers and heifers. Improvements in performance were not evident when laidlomycin propionate was fed at only 3 mg/kg. However, both average daily gain and feed conversion were improved by laidlomycin propionate within the range of 6 to 12 mg/kg of DM (P less than .001). Feed consumption was not substantially affected by inclusion of laidlomycin propionate in the diet. Improvements in ADG and feed conversion were greater on lower-energy diets than on higher-energy diets, but both these performance characteristics were improved regardless of the type of diet fed. Average daily gain was maximized with laidlomycin propionate at 6 mg/kg, whereas improvements in feed conversion were sustained through 12 mg/kg. Carcasses of cattle fed diets containing 6 to 12 mg/kg of laidlomycin propionate weighed 7.3 kg more (P less than .001) than carcasses of cattle fed the control diets. Yield grade and quality grade were not affected by laidlomycin propionate (P greater than .05). PMID- 2254210 TI - Mefluidide treatment of tall fescue pastures: intake and animal performance. AB - Twelve Hereford heifers were used in a grazing experiment to determine intake and digestibility of tall fescue forage treated with the plant growth regulator mefluidide. Additionally, steer and heifer performance were evaluated after grazing tall fescue pastures or consuming hay harvested from pastures treated with mefluidide. Average forage OM intake by heifers was 47% greater (P less than .05) during July and 50% greater (P less than .05) during August for mefluidide treated pastures than for untreated pastures. In vitro OM digestibility and indigestible ADF were compared for their ability to predict forage intake. The in vitro digestibility method produced more realistic intake data than the indigestible ADF method; however, trends in estimated forage intake were similar for both methods. Total tract particulate matter passage rates were similar (P greater than .10; 4.5 vs 4.1%/h), but mean retention times were shorter (P less than .05; 37.0 vs 46.9 h) when heifers grazed mefluidide-treated tall fescue. Steers grazing mefluidide-treated forage had greater (P less than .05) total weight gains than did steers grazing untreated tall fescue during a 168-d study (86 vs 69 kg). Heifers fed hay harvested from mefluidide-treated pastures also exhibited similar improvements in gain (49 vs 38 kg) because of increased (P less than .05) forage consumption (8.3 vs 7.3 kg/d) and greater (P less than .05) forage OM digestibility (65 vs 61%). Mefluidide treatment of tall fescue in early spring prolonged higher-quality herbage into midsummer and resulted in greater forage intake and animal performance. PMID- 2254211 TI - Mefluidide treatment of tall fescue pastures: forage quality. AB - Spring application of a plant growth regulator, mefluidide, to tall fescue (Festuca arundinacea Schreb.) pastures grazed from May to September reduced (P less than .05) available DM and digestible OM per hectare by 51 and 41%, respectively, compared to untreated pastures. However, seasonal averages for N, Ca and P content and in vitro OM disappearance (OMD) were greater (P less than .05) and NDF was lower (P less than .05) in tall fescue from mefluidide-treated pastures than in untreated pastures. Compared to hand-clipped samples, esophageal extrusa of tall fescue was 63% higher (P less than .05) in N (2.7 vs 1.7%) and 26% lower (P less than .05) in NDF (52.6 vs 69.9%) than hand-clipped tall fescue samples, regardless of treatment. Extrusa and hand-clipped herbage samples were similar (P greater than .10) in OMD during May and September, but OMD of extrusa was greater (P less than .05) during June, July and August compared to clipped samples. As a consequence of preventing stem elongation and seedhead formation earlier in the growing season, mefluidide treatment of tall fescue maintained forage quality at a higher level during midsummer. PMID- 2254212 TI - Digestion of soybean meal and canola meal protein and amino acids in the digestive tract of young ruminants. AB - Eight male Holstein calves (body weight 68 +/- 5 kg; age 75 +/- 6 d), each with a permanent re-entrant pancreatic cannula and T-type ileal and duodenal cannulas, were used in a crossover design with four animals per group to determine amino acid kinetics and digestibilities in the digestive tract of calves fed soybean meal (SBM) and canola meal (CM) protein. The SBM and CM diets were fed twice daily at a level of 900 g at each feeding time (air-dry basis). With the exception of methionine, crude protein and amino acid flows at the proximal duodenum, expressed as a percentage of intake, were not influenced by dietary protein source. Apparent ileal and total tract digestibilities of CP and amino acids were reduced (P less than .05) by feeding CM compared to SBM, but apparent ileal digestibility of methionine was not affected by dietary protein source. Except for methionine, net disappearance of all amino acids in the small intestine, relative to the amount fed, was higher for the SBM diet than for the CM diet. Net disappearance or synthesis of amino acids in the large intestine were not affected by dietary protein source. Similarly, dietary protein source did not affect (P greater than .05) the secretion of pancreatic juice or concentrations of protein, chymotrypsin and trypsin in pancreatic juice. Soybean meal protein has higher ileal and total gastrointestinal tract digestibility than CM protein for young, growing calves. PMID- 2254213 TI - Comparison of corn with four sorghum grain hybrids: site and extent of digestion in steers. AB - Four diverse sorghum hybrids (yellow, cream, hetero-yellow and red) and corn grain were dry-rolled and fed in an 85% grain diet to Angus-Hereford steers (241 kg) equipped with ruminal and double L-type duodenal and ileal cannulas to compare the effects of grain source on site and extent of digestion. Yellow (yel) has a homozygous yellow endosperm, with a yellow seed coat, whereas cream and hetero-yellow (het-yel) have a heterozygous yellow endosperm with white and red seed coats, respectively. Red has a homozygous white endosperm with a red seed coat. Diets were fed at 2% of initial BW (DM basis) in a 5 x 5 Latin square. Total digestive tract starch digestibility (%) was greater (P less than .05) for corn (92.5) than for red (84.3), yel (84.3) and het-yel (82.9) but not greater (P greater than .10) than for cream (87.9). Ruminal starch digestibility (%) was greater (P less than .10) for corn (85.8) than for sorghum hybrids (69.1). Pre cecal starch digestibility (%) was greater (P less than .05) for corn (90.6) than for het-yel (76.2), red (74.8) and yel (74.1). Ruminal escape (%) of grain N was greater (P less than .10) for red (79.9) than for het-yel (69.2), cream (66.5) and yel (66.1), with corn (53.6) being less (P less than .10) than sorghum hybrids. Pre-cecal and total tract non-NH3 N digestibilities (%) were not altered (P greater than .10) by grain source. Hybrid of sorghum altered site and extent of starch digestion and ruminal escape of grain N; hybrids had estimated gain:feed ratios that were 81 to 93% of those of rolled corn grain. PMID- 2254214 TI - Animal welfare, animal rights and agriculture. AB - The past decade has witnessed a major revolution in social concern with animals. Philosophically, this revolution entails a significant revision in traditional ways of conceiving our moral obligations to other creatures. Therefore, it is necessary to understand the social and conceptual basis for what is widely termed "animal rights." The agricultural community has mistakenly tended to dismiss this new thinking as fringe and emotionally based. In actuality, it is a natural extension of earlier social thought. The case of new laws regulating biomedical research illustrates the rapidity of social change in this area, as do recent developments in European regulation of agriculture. The relevance of this new moral thought to what has hitherto been understood purely in economic terms must be assimilated by the American agricultural community before the agricultural community can respond appropriately and non-reactively. PMID- 2254215 TI - Teaching animal welfare in the land grant universities. AB - Colleges and universities have an obligation to teach the basis of animal husbandry and welfare and must prepare students so that they can respond effectively to challenges by proponents of the animal welfare and animal rights movements. Veterinary curricula must now contain formal instruction in professional ethics and humane stewardship of animals for accreditation by the American Veterinary Medical Association. It is helpful if students have an understanding of farm animal behavior, stress physiology and methods of assessing welfare prior to learning about the animal welfare/rights movement's philosophies and issues. A review of early judicial practices, "classical" Judeo-Christian philosophy, the philosophy of Rene Descartes, Jeremy Bentham, Albert Schweitzer, and current philosophers and the entertainment media places the movements in perspective. Students should be familiar with such concepts as the mind-body controversy, equality of suffering, self-awareness or intelligence, and speciesism. After acquiring an appreciation of the basics, a knowledge of the issues facing animal agriculture and the arguments for and against each issue are necessary. Graduates of colleges of agriculture need to realize the potential effects the movements can have and take the initiative to improve the image of animal agriculture. PMID- 2254216 TI - Educational methodology in dealing with animal rights and welfare in public service. AB - Animal rights and animal welfare have biological, economic, social, philosophical, emotional, political, legal and policy dimensions. Hundred of organizations are active in some aspect of these issues. Viewpoints range in a continuum from animal rights advocates to livestock producers. One long-range goal is to increase understandings of both the benefits and the costs of animal rights and animal welfare for individuals and society. In the short-range, solutions and (or) alternatives for crisis situations are needed. Key aspects for using education as a means to solve these problems are 1) characterization of the issue(s), 2) identification of the audience(s), 3) selection of communications media and channels, and 4) development of appropriate educational materials. Task forces of educators and clientele for audience involvement are essential in planning and testing educational methods. When situations involve political, legal, and policy aspects, two task forces are needed: 1) a multidisciplinary educational group of scientists and educators to prepare objective usable information, and 2) an action group of clientele to communicate potential impacts of political, legal or policy action. Liaison between two groups is very important. Contemporary examples are presented. PMID- 2254217 TI - Multiple mechanisms of erythromycin resistance. PMID- 2254218 TI - Transport of the antimycotic 5-fluorocytosine and related substances in fungi. PMID- 2254219 TI - Risk/benefit analysis of quinolone use in children: the effect on diarthrodial joints. PMID- 2254220 TI - Effect of growth-rate on resistance of gram-negative biofilms to cetrimide. AB - A method of cell culture, which allows control of growth rate for sessile Gram negative populations, has been employed to assess the sensitivity of Escherichia coli biofilms to the antiseptic compound, cetrimide. Growth-rate-dependent changes in sensitivity were compared for chemostat-grown, planktonic cells, for cells resuspended from the biofilm and also for newly formed daughter cells shed from the biofilm during its growth and development. Susceptibility to cetrimide decreased in all instances with increases in growth-rate up to mu = 0.15 h-1. As growth rate was increased beyond this value then sensitivity increased in proportion to the rate of division. At rates of growth less than mu = 0.15 h-1 the susceptibility of the biofilm-derived cells and their offspring was significantly less than that of cells of planktonic origin. PMID- 2254221 TI - Antimicrobial susceptibility testing of Haemophilus influenzae. Improvement of accuracy of the disc diffusion test. AB - A national quality control study was performed in 1986 to investigate the standard of performance of the disc diffusion antimicrobial susceptibility testing of Haemophilus influenzae in Sweden. The accuracy of susceptibility interpretations was unacceptably low. A new standardized method for susceptibility testing of H. influenzae was then worked out, and a new method of setting interpretive zone breakpoints was introduced. The susceptibility category of the main population of clinical isolates was determined according to the MIC50 of the strains. The zone histograms of clinical isolates from five reference laboratories were used for the calculation of interpretive breakpoints. For instance, for susceptible strains the mean of the combined zone values from these laboratories +/- 2 S.D. covered the zone range of the susceptible group, and one more S.D. below covered the intermediate/indeterminate group. The new zone breakpoints would place the main population of clinical isolates in the correct susceptibility group, and even make it possible to detect strains with different degrees of reduced susceptibility in the routine test. In a follow-up quality control study in 1988 the interpretive errors for clinical isolates were eliminated for all antibiotics except doxycycline in some laboratories. Laboratory-related zone breakpoints for doxycycline calculated by the single strain regression analysis method led to correct susceptibility interpretations also in these cases. PMID- 2254222 TI - Effect of clindamycin on the intracellular bactericidal capacity of human peritoneal macrophages. AB - Survival and growth of bacteria within peritoneal macrophages has been implicated as a cause of recurrence and relapse of Staphylococcus epidermidis peritonitis during peritoneal dialysis. We studied the effect of orally administered clindamycin (known to enter and concentrate in phagocytes) on the intracellular killing of S. epidermidis by human peritoneal macrophages. Clindamycin (300 mg qid) was taken for one day by eight CAPD patients. Peritoneal macrophages were isolated from the effluents and their capacity to phagocytose and kill S. epidermidis was measured. In effluents containing clindamycin, the macrophages showed better uptake (32 vs 17%, P less than 0.01) and intracellular killing (70 vs 42%, P less than 0.01) of S. epidermidis compared with control after 1 h incubation. After 18 h S. epidermidis within peritoneal macrophages incubated with clindamycin, showed a further decrease in viability (-0.33 decrease in log cfu/ml). In contrast, control phagocytes allowed numbers of S. epidermidis to increase over 18 h (+1.46 increase in log cfu/ml; P less than 0.01 compared to clindamycin). Antibiotics with the ability to suppress intracellular bacterial growth should be studied for treatment of CAPD-related S. epidermidis peritonitis. PMID- 2254223 TI - Predominance of resistant oral streptococci in saliva and the effect of a single course of josamycin or erythromycin. AB - We have investigated the influence of the macrolides erythromycin and josamycin on the selection of resistant oral streptococci by sampling saliva of volunteers before and after oral administration of 1.5 g of either agent followed by a further 0.5 g of the same drug after 6 h, as in routine prophylaxis for oral or dental procedures. The small proportion of resistant organisms present before antibiotic administration increased substantially 48 h after the macrolides were given. After antibiotic administration mean counts of oral streptococci resistant to 1, 4 and 64 mg/l erythromycin were 23%, 17% and 6%, respectively, of the total numbers of streptococci isolated; after josamycin, the values were 13%, 6% and 4% respectively. The proportion of resistant streptococci then declined gradually but remained above pre-antibiotic levels three months later. Streptococci isolated on media containing 64 mg/l of macrolides were mainly Streptococcus sanguis and S. mitis with one isolate of S. salivarius; the majority were resistant to 256 mg/l erythromycin, josamycin, all other macrolides tested and clindamycin. Amoxycillin and pristinamycin were the only compounds tested that were inhibitory to these organisms at therapeutically attainable concentrations. PMID- 2254224 TI - Epidemiology of ciprofloxacin resistance among patients with methicillin resistant Staphylococcus aureus. AB - During the first twelve months after ciprofloxacin was introduced for clinical use at our institution, 65 new patients were found to be either infected or colonized by methicillin-resistant Staphylococcus aureus (MRSA) which were also ciprofloxacin resistant (CR-MRSA). Only 18 of these patients (28%) had been previously exposed to this antibiotic. Nine (50%) of the 18 patients had received ciprofloxacin for treatment for a pathogen other than MRSA. Although the initial cases of colonization or infection with CR-MRSA can be directly related to ciprofloxacin use, many of the subsequent cases of colonization and infection were not the consequence of ciprofloxacin therapy but rather hospital transmission of existing CR-MRSA. PMID- 2254225 TI - Correlations between consumption of antibiotics and methicillin resistance in coagulase negative staphylococci. AB - The correlation between antibiotic consumption, expressed in defined daily doses (DDD), and antibiotic resistance rates was studied, using 976 isolates of coagulase negative staphylococci (CNS) from human pathological material. Data from four hospitals, including 14 participating departments, were analysed for this purpose. Susceptibility tests were performed according to Dutch national standards, except for methicillin, which for the majority of isolates was tested according to adapted NCCLS standards. Resistance to methicillin was most frequent in Staphylococcus epidermidis (29%) and S. haemolyticus (16%). Among the departments, thoracic surgery (29-47%), surgical intensive care (68%) and neonatology (32%) scored highest. Significant correlations were found between percentages of methicillin resistance in CNS and consumption (DDD/month/bed) of (flu)cloxacillin (P0.008), of cephalosporins (P0.01) and of gentamicin (P0.005). (Flu)cloxacillin was used mainly prophylactically, cephalosporins and gentamicin therapeutically. Results were similar for S. epidermidis (n = 639) alone. There was no significant correlation between consumption and resistance to trimethoprim, erythromycin (P0.08) or gentamicin (P0.09). Analysis of data from individual patients showed significant differences in proportions of methicillin resistance rates in CNS, between use and non-use of penicillinase resistant beta lactams or gentamicin. It is concluded that clinical use of both (flu)cloxacillin and cephalosporins selects for methicillin resistant CNS. PMID- 2254226 TI - High prevalence of antibiotic resistant Escherichia coli in faecal samples of students in the south-east of The Netherlands. AB - From December 1988 to March 1989 172 faecal samples from first and second year students at the University of Limburg, Maastricht, The Netherlands, were collected and analysed for the presence of Escherichia coli strains resistant to ampicillin, sulphamethoxazole, tetracycline, trimethoprim and nitrofurantoin. In addition, the antibiotic susceptibility (MIC) to these agents and six other compounds (i.e. aminoglycosides, nitrofurantoin, nalidixic acid and cephalothin) was determined. The prevalence of resistance of the samples analysed ranged from 86% (i.e. 148 out of 172) for sulphamethoxazole to 25% for trimethoprim. The prevalence figures for ampicillin, tetracycline and nitrofurantoin resistance were 76%, 47% and 29%, respectively. The percentages of the faecal samples with a high proportion of E. coli (greater than 50% of the total number of E. coli) resistant to ampicillin, tetracycline and sulphamethoxazole were 8%, 11% and 37%, respectively. For nitrofurantoin and trimethoprim the figures were 3% and 1%, respectively. Of the isolated E. coli (n = 797), 84% was resistant to ampicillin, 82% resistant to sulphamethoxazole. The lowest percentages (9%) were observed for both nalidixic acid and nitrofurantoin. PMID- 2254227 TI - Penicillin-binding protein (PBP) 2 and the post-antibiotic effect of carbapenems. PMID- 2254228 TI - Loss of ciprofloxacin's second killing action in Escherichia coli that have developed 4-quinolone resistance during therapy. PMID- 2254229 TI - Problems with Iso-Sensitest agar. PMID- 2254230 TI - In-vitro activity of cefotaxime against clinical isolates of Yersinia enterocolitica biotype 4, serotype 03. PMID- 2254231 TI - Fluconazole concentration in joint fluid during successful treatment of Candida albicans septic arthritis. PMID- 2254232 TI - Enterococci from blood cultures during 1980-1989: susceptibility to ampicillin, penicillin and vancomycin. PMID- 2254233 TI - Do self-help groups help? AB - There is an increasing number of self-help groups. The British Diabetic Association has recently supported the development of such groups for people with diabetes. In the present research, eight self-help groups for diabetics were studied. This report describes the reasons given by group leaders for wanting to start such groups and analyses what was discussed in them. The observations reported suggest that the groups provided social-psychological support. PMID- 2254234 TI - Post-operative depression and coronary bypass surgery. AB - Factors pertaining to post-surgical rehabilitation were investigated. These included personality, mental, and pain issues. The investigation covered the first year of bypass operations. SUBJECTS: 60 patients undergoing coronary artery bypass graft (CABE) operations. INSTRUMENTS: a questionnaire, a personality inventory (MMPI), and a test of mental status (Raven's). The questionnaire was first administered a few days before and then after surgery and then repeated at intervals of 3, 6, and 12 months after surgery. RESULTS: 76% were within normal limits on the Raven while 54% of those tested had significant depression. Both the depressed patients' dates of surgery and their ages were evenly distributed, and no significant differences were found between these and those not tested. Other MMPI results were that 36% scored above normal on the hysteria scale, 27% were quite anxious, and 24% were above average on the schizophrenia scale. The answers to the questionnaire items were relatively stable. In a comparison of the answers of the depressed versus the non-depressed, no significant differences were found. The reason for the depression is not apparent, but it is not considered to be the result of medication or of a greater severity of pain. The depression was not found to have affected the rehabilitation progress. PMID- 2254235 TI - Physical rehabilitation of the elderly blind patient. AB - OBJECTIVE: to evaluate the policy of admitting elderly blind patients with motor impairments for physical rehabilitation. DESIGN: retrospective chart review for comparisons between blind and visually intact patients with similar diagnoses. SETTING: geriatric rehabilitation hospital. PATIENTS: all patients with stroke, fractured hip, and lower limb amputation. EXCLUSIONS: none. ASSESSMENTS: walking ability and functional performance (ADL), using the Barthel Index. RESULTS: overall outcome in blind patients was only slightly less favourable than in the visually intact, although, in comparison with premorbid status, only just over half were ambulatory at discharge and functional independence was less common. CONCLUSIONS: elderly blind patients with motor impairments should be offered a trial by physical rehabilitation. PMID- 2254236 TI - Respiratory function in chronic hemiplegia. AB - Dynamic spirometry was examined in 23 non-smoking hemiplegic patients after the acute phase. The decrease of slow inspiratory forced capacity is related to motor impairment and does not vary with time. The forced inspiratory and expiratory vital capacities are similar to the slow inspiratory vital capacity in the first 6 months of the disease, but significantly decrease later independent of the motor impairment. The peak expiratory flow is highly variable but is clearly decreased, and is related to motor impairment. These results point to a restrictive respiratory syndrome due to mechanical limitation of thorax excursions caused by weakness, hypotonicity, and incoordination of the trunk musculature. The importance of long-term physiotherapy of the trunk is emphasized. PMID- 2254237 TI - Risk factors and causes of stroke in young women in Israel. AB - OBJECTIVE: to identify risk factors and likely causes for stroke in young women, as a basis for designing a strategy for stroke incidence reduction. DESIGN: retrospective chart review for comparisons between the sexes. SETTING: general and rehabilitation hospitals. PATIENTS: all 263 patients aged 17-45 years with stroke over a 15-year period. EXCLUSIONS: patients seen at 14 general hospitals who were not referred to the Loewenstein. ASSESSMENTS: data on sociodemographic, anamnestic, and clinical aspects. RESULTS: stroke under the age of 30 years was more frequent in women, and in them the risk factors differed from those in an older population. The most frequent cause of stroke in the younger women was embolism, in the majority on the basis of a rheumatic valvular defect, whereas in young men the usual cause was atherosclerosis. CONCLUSIONS: opportunities for preventive initiatives have not always been grasped, and more attention should be directed to such possibilities. PMID- 2254238 TI - Establishing a head-injury rehabilitation service. PMID- 2254239 TI - Location of the bglA gene on the physical map of Escherichia coli. PMID- 2254240 TI - Location of gyrA on the physical map of the Escherichia coli chromosome. PMID- 2254241 TI - Location of icdA and fadR on the physical map of Escherichia coli. PMID- 2254242 TI - Location of an ntr-like gene on the physical map of Escherichia coli. PMID- 2254243 TI - Polymorphism in Brucella spp. due to highly repeated DNA. AB - The species of Brucella are very closely related, but Brucella ovis does not express detectable amounts of a protein, designated BCSP31, that is common to the other species. We studied the lack of expression of BCSP31 by Southern analysis. DNAs from the B. ovis culture collection strains and field isolates were probed with a 1.3-kb HindIII fragment encoding BCSP31 of Brucella abortus. The probe hybridized to a 1.6-kb HindIII fragment of all B. ovis strains tested, showing that the gene is present in B. ovis but occurs on a larger restriction fragment. DNA linkage studies and restriction mapping of the cloned polymorphic region of B. ovis showed that the polymorphism was due to a DNA insertion of approximately 0.9 kb at a site downstream of the BCSP31-coding region. When the 1.6-kb polymorphic B. ovis fragment was used to probe a HindIII Southern blot of cellular DNA of strains of B. ovis and of B. abortus, at least 24 fragments of B. ovis and 6 fragments of B. abortus hybridized to the inserted DNA. Specimens of B. ovis collected over a 30-year period on two continents had similar hybridization patterns. The large difference between B. ovis and B. abortus in the number of copies of the repeated DNA is interesting in the context of the closeness of the Brucella species. PMID- 2254244 TI - Growth-phase-dependent expression of the Pseudomonas putida TOL plasmid pWW0 catabolic genes. AB - Pseudomonas putida TOL plasmid pWW0 catabolic genes are clustered into two operons. The first, the upper operon, is controlled by the xylR regulatory gene, whereas the second, the meta operon, is controlled by the xylS regulatory gene. The xylS gene itself is subjected to control by xylR. In this study, we show that the TOL catabolic operons were poorly induced in cells growing at the early exponential-growth phase but strongly induced in cells at late-exponential-growth phase. We constructed fusions of four TOL promoters, Pm (the promoter of the meta operon), Pu (the promoter of the upper operon), Ps (the promoter of the xylS regulatory gene), and Pr (the promoter of the xylR regulatory gene) with lacZ and examined, in Escherichia coli and P. putida, the expression of these promoters in relation to the growth phase. Expression from Pm, Pu, Ps, and Pr was almost constant if the host cells did not carry either xylS or xylR. Similarly, expression of Pm and Pu in P. putida in the absence of XylS and XylR was constant during the growth of the cells. XylS-dependent transcription of Pm and XylR dependent transcription of Ps and Pu, in contrast, varied with the growth phase. This observation suggested that the interaction of XylS and XylR with target promoters or with RNA polymerases was influenced by the growth phase. The nature of the signal which triggers the growth-phase-dependent regulation was not clear. A change in the oxygen partial pressure was not responsible for the regulation. E. coli mutants defective in relA, crp, and cya exhibited growth-phase-dependent expression of the TOL catabolic genes, indicating that cyclic AMP and relA dependent synthesis of ppGpp are not involved in this phenomenon. PMID- 2254245 TI - Proton motive force, energy recycling by end product excretion, and metabolic uncoupling during anaerobic growth of Pseudomonas mendocina. AB - Batch cultures of Pseudomonas mendocina, grown in rich medium with glucose excess, showed metabolic differences dependent upon whether the growth conditions were aerobic or anaerobic, with or without added electron acceptor. Under anaerobic conditions in the absence of nitrate, P. mendocina reached the stationary phase of growth after 2 or 3 days, followed by a stationary phase of 4 to 5 days. Under these conditions, a mixed-type fermentative metabolism (formic, lactic, and acetic acids) appeared. A fivefold-higher specific rate of glucose consumption and eightfold-higher production of organic acids, compared with aerobic cultures, were shown by this microorganism growing anaerobically in the absence of exogenous electron acceptors. The gradients of organic acid produced by P. mendocina under these conditions reached a maximum (lactate, 180 mV; formate, 150 mV; acetate, 215 mV) between days 2 and 3 of culture. The proton motive force (delta p) decreased during growth from -254 to -71 mV. The intracellular pH remained alkaline during the culture, reaching a steady-state value of 7.9. The gradients of organic acids apparently contributed to the generation of a delta p, which, according to the Energy Recycling Model (P. A. M. Michels, J. P. J. Michels, J. Boonstra, and W. N. Konings, FEMS Microbiol. Lett. 5:357-364, 1979), would produce an average energy gain of 1 or 1.5 mol of ATP equivalents per mol of glucose consumed with H+/ATP stoichiometry of 3 or 2, respectively. Low YATP and Yglucose values were observed, suggesting that an uncoupled metabolism exists; i.e., ATP produced by catabolic processes is not directly used for biomass synthesis. This metabolic uncoupling could be induced at least in part by organic acids and the ATP wastage could be induced by a membrane-bound ATPase involved in intracellular pH regulation. PMID- 2254246 TI - The balance between different peptidoglycan precursors determines whether Escherichia coli cells will elongate or divide. AB - The rodA(Sui) mutation allows cell division to take place at 42 degrees C in ftsI23 mutant cells, which produce a thermolabile penicillin-binding protein 3 (PBP3, the septation-specific peptidoglycan transpeptidase). We show here that the mutation in rodA is a single-base change from a glutamine to a chain termination (amber) codon, and that an amber suppressor (supE) present in the strain restores the ability to produce a reduced level of normal RodA protein. The reduced level of RodA is accompanied by an increase in the levels of two other proteins (PBP2 and PBP5) encoded by genes in the rodA operon. We show that an increased level of PBP5 is by itself sufficient to restore cell division to ftsI23 cells at 42 degrees C. Two other treatments were found to restore division capacity to the mutant: an increase in PBP6 (which is a D-alanine carboxypeptidase like PBP5) or suitable concentrations of D-cycloserine. All of the above treatments have the effect of reducing the number of pentapeptide side chains in peptidoglycan and increasing the number of tripeptides. We conclude that the effect of the rodA(Sui) mutation is to indirectly increase the availability of tripeptide side chains, which are used preferentially by PBP3 as acceptors in transpeptidation. A change in the proportions of different kinds of peptide side chain in the peptidoglycan can therefore determine whether cells will divide. PMID- 2254247 TI - Elucidation of the Erwinia uredovora carotenoid biosynthetic pathway by functional analysis of gene products expressed in Escherichia coli. AB - The most important function of carotenoid pigments, especially beta-carotene in higher plants, is to protect organisms against photooxidative damage (G. Britton, in T. W. Goodwin, ed., Plant Pigments--1988, 1988; N. I. Krinsky, in O. Isler, H. Gutmann, and U. Solms, ed., Carotenoids--1971, 1971). beta-Carotene also functions as a precursor of vitamin A in mammals (G. A. J. Pitt, in I. Osler, H. Gutmann, and U. Solms, ed., Carotenoids--1971, 1971). The enzymes and genes which mediate the biosynthesis of cyclic carotenoids such as beta-carotene are virtually unknown. We have elucidated for the first time the pathway for biosynthesis of these carotenoids at the level of enzyme-catalyzed reactions, using bacterial carotenoid biosynthesis genes. These genes were cloned from a phytopathogenic bacterium, Erwinia uredovora 20D3 (ATCC 19321), in Escherichia coli and located on a 6,918-bp fragment whose nucleotide sequence was determined. Six open reading frames were found and designated the crtE, crtX, crtY, crtI, crtB, and crtZ genes in reference to the carotenoid biosynthesis genes of a photosynthetic bacterium, Rhodobacter capsulatus; only crtZ had the opposite orientation from the others. The carotenoid biosynthetic pathway in Erwinia uredovora was clarified by analyzing carotenoids accumulated in E. coli transformants in which some of these six genes were expressed, as follows: geranylgeranyl PPiCrtB----prephytoene PPiCrtE----phytoeneCrtI---- lycopeneCrtY--- beta-caroteneCrtZ----zeaxanthinCrtX--- -zeaxanthin-beta- diglucoside. The carotenoids in this pathway appear to be close to those in higher plants rather than to those in bacteria. Also significant is that only one gene product (CrtI) for the conversion of phytoene to lycopene is required, a conversion in which four sequential desaturations should occur via the intermediates phytofluene, zeta-carotene, and neurosporene. PMID- 2254248 TI - Regulation of transcription of katE and katF in Escherichia coli. AB - Fusion plasmids with lacZ under the control of the katE (encoding catalase or hydroperoxidase HPII) and katF (encoding a sigma factor-like protein required for katE expression) promoters were constructed. Expression from both katE and katF promoters was low in rich medium but elevated in poor medium during log-phase growth. Furthermore, the slowdown in growth as cells entered the stationary phase in rich medium, a result of carbon source depletion, was associated with an increase in katE and katF expression. A simple reduction in the carbon source level as the cells entered the stationary phase was not responsible for the increase in expression, because transferring the culture to a medium with no glucose did not induce expression from either promoter. Spent rich medium from stationary-phase cells was capable of inducing expression, as were simple aromatic acids such as benzoate, o-hydroxybenzoate, and p-aminobenzoate added to new medium. Anaerobiosis did not cause an increase in expression, nor did it significantly change the pattern of expression. Regardless of the medium, katF expression was always turned on before or coincidently with katE expression; in the presence of benzoate katF was fully induced, whereas katE was only partially induced, suggesting that a factor in addition to KatF protein was involved in katE expression. During prolonged aerobic incubation, cells lacking katF died off more rapidly than did cells lacking either katE or katG. PMID- 2254249 TI - Overproduction of release factor reduces spontaneous frameshifting and frameshift suppression by mutant elongation factor Tu. AB - Mutant forms of elongation factor Tu encoded by tufA8 and tufB103 in Salmonella typhimurium cause suppression of some but not all frameshift mutations. All of the suppressed mutations in S. typhimurium have frameshift windows ending in the termination codon UGA. Because both tufA8 and tufB103 are moderately efficient UGA suppressors, we asked whether the efficiency of frameshifting is influenced by the level of misreading at UGA. We introduced plasmids synthesizing either one of the release factors into strains in which the tuf mutations suppress a test frameshift mutation. We found that overproduction of release factor 2 (which catalyzes release at UGA and UAA) reduced frameshifting promoted by the tuf mutations at all sites tested. However, at one of these sites, trpE91, overproduction of release factor 1 also reduced suppression. The spontaneous level of frameshift "leakiness" at three sites in trpE, each terminating in UGA, was reduced in strains carrying the release factor 2 plasmid. We conclude that both spontaneous and suppressor-enhanced reading-frame shifts are influenced by the activity of peptide chain release factors. However, the data suggest that the effect of release factor on frameshifting does not necessarily depend on the presence of the normal triplet termination signal. PMID- 2254250 TI - Cloning and sequencing of the sacA gene: characterization of a sucrase from Zymomonas mobilis. AB - The Zymomonas mobilis gene (sacA) encoding a protein with sucrase activity has been cloned in Escherichia coli and its nucleotide sequence has been determined. Potential ribosome-binding site and promoter sequences were identified in the region upstream of the gene which were homologous to E. coli and Z. mobilis consensus sequences. Extracts from E. coli cells, containing the sacA gene, displayed a sucrose-hydrolyzing activity. However, no transfructosylation activity (exchange reaction or levan formation) could be detected. This sucrase activity was different from that observed with the purified extracellular protein B46 from Z. mobilis. These two proteins showed different electrophoretic mobilities and molecular masses and shared no immunological similarity. Thus, the product of sacA (a polypeptide of 58.4-kDa molecular mass) is a new sucrase from Z. mobilis. The amino acid sequence, deduced from the nucleotide sequence of sacA, showed strong homologies with the sucrases from Bacillus subtilis, Salmonella typhimurium, and Vibrio alginolyticus. PMID- 2254251 TI - Novel two-component transmembrane transcription control: regulation of iron dicitrate transport in Escherichia coli K-12. AB - Citrate and iron have to enter only the periplasmic space in order to induce the citrate-dependent iron(III) transport system of Escherichia coli. The five transport genes fecABCDE form an operon and are transcribed from fecA to fecE. Two genes, termed fecI and fecR, that mediate induction by iron(III) dicitrate have been identified upstream of fecA. The fecI gene encodes a protein of 173 amino acids (molecular weight, 19,478); the fecR gene encodes a protein of 317 amino acids (molecular weight, 35,529). Chromosomal fecI::Mu d1 mutants were unable to grow with iron(III) dicitrate as the sole iron source and synthesized no FecA outer membrane receptor protein. Growth was restored by transformation with plasmids encoding fecI or fecI and fecR. FecA and beta-galactosidase syntheses under transcription control of the fecB gene (fecB::Mu d1) were constitutive in fecI transformants and were regulated by iron(III) dicitrate in fecI fecR transformants. The amino acid sequence of the FecI protein contains a region close to the carboxy-terminal end for which a helix-turn-helix motif is predicted, which is typical for DNA-binding regulatory proteins. The FecI protein was found in the membrane, and the FecR protein was found in the periplasmic fraction. It is proposed that the FecR protein is the sensor that recognizes iron(III) dicitrate in the periplasm. The FecI protein activates fec gene expression by binding to the fec operator region. In the absence of citrate, FecR inactivates FecI. The lack of sequence homologies to other transmembrane signaling proteins and the location of the two proteins suggest a new type of transmembrane control mechanism. PMID- 2254252 TI - Deletion analysis of the 51-kilodalton protein of the Bacillus sphaericus 2362 binary mosquitocidal toxin: construction of derivatives equivalent to the larva processed toxin. AB - Bacillus sphaericus 2362 produces a binary toxin consisting of 51- and 42-kDa proteins, both of which are required for toxicity to mosquito larvae. Upon ingestion by larvae, these proteins are processed to 43 and 39 kDa, respectively. Using site-directed mutagenesis, we have obtained N- and C-terminal deletions of the 51-kDa protein and expressed them in B. subtilis by using the subtilisin promoter. Removal of 21 amino acids from the N terminus and 53 amino acids from the C terminus resulted in a protein with the same electrophoretic properties as the 43-kDa degradation product which accumulates in the guts of mosquito larvae. This protein was toxic only in the presence of the 42-kDa protein. A deletion of 32 amino acids at the N terminus combined with a 53-amino-acid deletion at the C terminus resulted in a protein which retained toxicity. Toxicity was lost upon a further deletion of amino acids at potential chymotrypsin sites (41 at the N terminus, 61 at the C terminus). Comparison of the processing of the 51- and the 42-kDa proteins indicated that in spite of their sequence similarity proteolysis occurred at different sites. PMID- 2254253 TI - Purification, cloning, and primary structure of an enantiomer-selective amidase from Brevibacterium sp. strain R312: structural evidence for genetic coupling with nitrile hydratase. AB - An enantiomer-selective amidase active on several 2-aryl and 2-aryloxy propionamides was identified and purified from Brevibacterium sp. strain R312. Oligonucleotide probes were designed from limited peptide sequence information and were used to clone the corresponding gene, named amdA. Highly significant homologies were found at the amino acid level between the deduced sequence of the enantiomer-selective amidase and the sequences of known amidases such as indoleacetamide hydrolases from Pseudomonas syringae and Agrobacterium tumefaciens and acetamidase from Aspergillus nidulans. Moreover, amdA is found in the same orientation and only 73 bp upstream from the gene coding for nitrile hydratase, strongly suggesting that both genes are part of the same operon. Our results also showed that Rhodococcus sp. strain N-774 and Brevibacterium sp. strain R312 are probably identical, or at least very similar, microorganisms. The characterized amidase is an apparent homodimer of Mr 2 x 54,671 which exhibited under our conditions a specific activity of about 13 to 17 mumol of 2-(4 hydroxyphenoxy)propionic R acid formed per min per mg of enzyme from the racemic amide. Large amounts of an active recombinant enzyme could be produced in Escherichia coli at 30 degrees C under the control of an E. coli promoter and ribosome-binding site. PMID- 2254254 TI - A novel Bacillus thuringiensis gene encoding a Spodoptera exigua-specific crystal protein. AB - Only one of the four lepidoptera-specific crystal protein subclasses (CryIC) Bacillus thuringiensis was previously shown to be highly toxic against several Spodoptera species. By using a cryIC-derived nucleotide probe, DNA from 25 different strains of B. thuringiensis was screened for the presence of homologous sequences. A putative crystal protein gene, considerably different from the cryIC gene subclass, was identified in the DNA of strain 4F1 (serotype kenyae) and cloned in Escherichia coli. Its nucleotide sequence was determined and appeared to contain several features typical for a crystal protein gene. Furthermore, the region coding for the N-terminal part of the putative toxic fragment showed extensive homology to subclass cryIA sequences derived from gene BtII, whereas the region coding for the C-terminal part appeared to be highly homologous to the cryIC gene BtVI. With an anti-crystal protein antiserum, a polypeptide of the expected size could be demonstrated in Western immunoblots, onto which a lysate of E. coli cells harboring the putative gene, now designated as BtXI, had been transferred. Cells expressing the gene appeared to be equally toxic against larvae of Spodoptera exigua as recombinant cells expressing the BtVI (cryIC) encoded crystal protein. However, no toxicity against larvae of Heliothis virescens, Mamestra brassicae, or Pieris brassicae could be demonstrated. The nucleotide sequence analysis and the toxicity studies showed that this novel crystal protein gene falls into a new cryl gene subclass. We propose that this subclass be referred to as cryIE. PMID- 2254255 TI - Nitrogenase in the archaebacterium Methanosarcina barkeri 227. AB - The discovery of nitrogen fixation in the archaebacterium Methanosarcina barkeri 227 raises questions concerning the similarity of archaebacterial nitrogenases to Mo and alternative nitrogenases in eubacteria. A scheme for achieving a 20- to 40 fold partial purification of nitrogenase components from strain 227 was developed by using protamine sulfate precipitation, followed by using a fast protein liquid chromatography apparatus operated inside an anaerobic glove box. As in eubacteria, the nitrogenase activity was resolved into two components. The component 1 analog had a molecular size of approximately 250 kDa, as estimated by gel filtration, and sodium dodecyl sulfate-polyacrylamide gels revealed two predominant bands with molecular sizes near 57 and 62 kDa, consistent with an alpha 2 beta 2 tetramer as in eubacterial component 1 proteins. For the component 2 analog, a molecular size of approximately 120 kDa was estimated by gel filtration, with a subunit molecular size near 31 kDa, indicating that the component 2 protein is a tetramer, in contrast to eubacterial component 2 proteins, which are dimers. Rates of C2H2 reduction by the nearly pure subunits were 1,000 nmol h-1 mg of protein-1, considerably lower than those for conventional Mo nitrogenases but similar to that of the non-Mo non-V nitrogenase from Azotobacter vinelandii. Strain 227 nitrogenase reduced N2 at a higher rate per electron than it reduced C2H2, also resembling the non-Mo non-V nitrogenase of A. vinelandii. Ethane was not produced from C2H2. NH4+ concentrations as low as 10 microM caused a transient inhibition of C2H2 reduction by strain 227 cells. Antiserum against component 2 Rhodospirillum rubrum nitrogenase was found to cross-react with component 2 from strain 227, and Western immunoblots using this antiserum showed no evidence for covalent modification of component 2. Also, extracts of strain 227 cells prepared before and after switch-off had virtually the same level of nitrogenase activity. In conclusion, the nitrogenase from strain 227 is similar in overall structure to the eubacterial nitrogenases and shows greatest similarity to alternative nitrogenases. PMID- 2254256 TI - A new Vibrio fischeri lux gene precedes a bidirectional termination site for the lux operon. AB - The DNA downstream of the lux structural genes in the Vibrio fischeri lux operon has been sequenced and a new lux gene (luxG) has been identified. A hairpin loop that begins with a poly(A) region and ends with a poly(T) region and thus can function as a bidirectional termination site for luxG and a convergent gene is located immediately downstream of luxG. 3' S1 nuclease mapping has demonstrated that the luxG mRNA was induced in a cell-density-dependent fashion consistent with it being part of the lux system and that the lux mRNA terminated immediately after the hairpin loop. The mRNA coded by an open reading frame convergent to luxG on the complementary strand was also shown by S1 nuclease mapping to overlap the lux mRNA for at least 20 nucleotides before termination. Expression of DNA containing the hairpin loop, placed between a strong promoter and a reporter gene and transferred by conjugation into luminescent bacteria, demonstrated the very high efficiency of termination by this hairpin loop oriented in either direction. These results also demonstrate that the organization of the genes at the 3' ends of the lux operons of V. fischeri and V. harveyi has clearly diverged. PMID- 2254257 TI - Comparative genetic organization of incompatibility group P degradative plasmids. AB - Plasmids that encode genes for the degradation of recalcitrant compounds are often examined only for characteristics of the degradative pathways and ignore regions that are necessary for plasmid replication, incompatibility, and conjugation. If these characteristics were known, then the mobility of the catabolic genes between species could be predicted and different catabolic pathways might be combined to alter substrate range. Two catabolic plasmids, pSS50 and pSS60, isolated from chlorobiphenyl-degrading strains and a 3 chlorobenzoate-degrading plasmid, pBR60, were compared with the previously described IncP group (Pseudomonas group P-1) plasmids pJP4 and R751. All three of the former plasmids were also members of the IncP group, although pBR60 is apparently more distantly related. DNA probes specific for known genetic loci were used to determine the order of homologous loci on the plasmids. In all of these plasmids the order is invariant, demonstrating the conservation of this "backbone" region. In addition, all five plasmids display at least some homology with the mercury resistance transposon, Tn501, which has been suggested to be characteristic of the beta subgroup of the IncP plasmids. Plasmids pSS50 and pSS60 have been mapped in detail, and repeat sequences that surround the suspected degradation genes are described. PMID- 2254258 TI - Complete nucleotide sequence and polypeptide analysis of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. AB - Pseudomonas sp. strain CF600 metabolizes phenol and some of its methylated derivatives via a plasmid-encoded phenol hydroxylase and meta-cleavage pathway. The genes encoding the multicomponent phenol hydroxylase of this strain are located within a 5.5-kb SacI-NruI fragment. We report the nucleotide sequence and the polypeptide products of this 5.5-kb region. A combination of deletion analysis, expression of subfragments in tac expression vectors, and identification of polypeptide products in maxicells was used to demonstrate that the polypeptides observed are produced from the six open reading frames identified in the sequence. Expression of phenol hydroxylase activity in a laboratory Pseudomonas strain allows growth on phenol, owing to expression of this enzyme and the chromosomally encoded ortho-cleavage pathway. This system, in conjunction with six plasmids that each expressed all but one of the polypeptides, was used to demonstrate that all six polypeptides are required for growth on phenol. PMID- 2254259 TI - In vitro analysis of polypeptide requirements of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. AB - An in vitro study of the multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600 was performed. Phenol-stimulated oxygen uptake from crude extracts was strictly dependent on the addition of NAD(P)H and Fe2+ to assay mixtures. Five of six polypeptides required for growth on phenol were necessary for in vitro activity. One of the polypeptides was purified to homogeneity and found to be a flavin adenine dinucleotide containing iron-sulfur protein with significant sequence homology, at the amino terminus, to plant-type ferredoxins. This component, as in other oxygenase systems, probably functions to transfer electrons from NAD(P)H to the iron-requiring oxygenase component. Phenol hydroxylase from this organism is thus markedly different from bacterial flavoprotein monooxygenases commonly used for hydroxylation of other phenolic compounds, but bears a number of similarities to multicomponent oxygenase systems for unactivated compounds. PMID- 2254260 TI - Osmoregulation in Agrobacterium tumefaciens: accumulation of a novel disaccharide is controlled by osmotic strength and glycine betaine. AB - We have investigated the mechanism of osmotic stress adaptation (osmoregulation) in Agrobacterium tumefaciens biotype I (salt-tolerant) and biotype II (salt sensitive) strains. Using natural-abundance 13C nuclear magnetic resonance spectroscopy, we identified all organic solutes that accumulated to significant levels in osmotically stressed cultures. When stressed, biotype I strains (C58, NT1, and A348) accumulated glutamate and a novel disaccharide, beta fructofuranosyl-alpha-mannopyranoside, commonly known as mannosucrose. In the salt-sensitive biotype II strain K84, glutamate was observed but mannosucrose was not. We speculate that mannosucrose confers the extra osmotic tolerance observed in the biotype I strains. In addition to identifying the osmoregulated solutes that this species synthesizes, we investigated the ability of A. tumefaciens to utilize the powerful osmotic stress protectant glycine betaine when it is supplied in the medium. Results from growth experiments, nuclear magnetic resonance spectroscopy, and a 14C labeling experiment demonstrated that in the absence of osmotic stress, glycine betaine was metabolized, while in stressed cultures, glycine betaine accumulated intracellularly and conferred enhanced osmotic stress tolerance. Furthermore, when glycine betaine was taken up in stressed cells, its accumulation caused the intracellular concentration of mannosucrose to drop significantly. The possible role of osmoregulation of A. tumefaciens in the transformation of plants is discussed. PMID- 2254261 TI - Characterization of an Enterococcus hirae penicillin-binding protein 3 with low penicillin affinity. AB - Enterococcus hirae S185, a clinical isolate from swine intestine, exhibits a relatively high resistance to penicillin and contains two 77-kDa penicillin binding proteins 3 of high (PBP 3s) and low (PBP 3r) affinity to penicillin, respectively. A laboratory mutant S185r has been obtained which overproduces PBP 3r and has a highly increased resistance to penicillin. Peptide fragments specifically produced by trypsin and SV8 protease digestions of PBP 3r were isolated, and the amino acid sequences of their amino terminal regions were determined. On the basis of these sequences, oligonucleotides were synthesized and used as primers to generate, by polymerization chain reaction, a 233-bp DNA fragment the sequence of which translated into a 73-amino-acid peptide segment of PBP 3r. These structural data led to the conclusion that the E. hirae PBP 3r and the methicillin-resistant staphylococcal PBP 2' are members of the same class of high-Mr PBPs. As shown by immunological tests, PBP 3r is not related to PBP 3s but, in contrast, is related to the 71-kDa PBP 5 of low penicillin affinity which is responsible for penicillin resistance in E. hirae ATCC 9790 and R40. PMID- 2254262 TI - SecB-independent export of Escherichia coli ribose-binding protein (RBP): some comparisons with export of maltose-binding protein (MBP) and studies with RBP-MBP hybrid proteins. AB - The efficient export of the Escherichia coli maltose-binding protein (MBP) is known to be SecB dependent, whereas ribose-binding protein (RBP) export is SecB independent. When the MBP and RBP signal peptides were exchanged precisely at the signal peptidase processing sites, the resultant RBP-MBP and MBP-RBP hybrid proteins both were efficiently exported in SecB+ cells. However, only MBP-RBP was efficiently exported in SecB- cells; RBP-MBP exhibited a significant export defect, a finding that was consistent with previous proposals that SecB specifically interacts with the mature moiety of precursor MBP to promote export. The relatively slow, totally posttranslational export mode exhibited by certain mutant RBP and MBP-RBP species in SecB+ cells was not affected by the loss of SecB. In contrast, MBP and RBP-MBP species with similarly altered signal peptides were totally export defective in SecB- cells. Both export-defective MBP and RBP MBP interfered with SecB-mediated protein export by depleting cells of functional SecB. In contrast, neither export-defective RBP nor MBP-RBP elicited such an interference effect. These and other data indicated that SecB is unable to interact with precursor RBP or that any interaction between these two proteins is considerably weaker than that of SecB with precursor MBP. In addition, no correlation could be established between a SecB requirement for export and PrlA mediated suppression of signal peptide export defects. Finally, previous studies have established that wild-type MBP export can be accomplished cotranslationally, whereas wild-type RBP export is strictly a posttranslational process. In this study, cotranslational export was not detected for either MBP-RBP or RBP-MBP. This indicates that the export mode exhibited by a given precursor protein (cotranslational versus posttranslational) is determined by properties of both the signal peptide and the mature moiety. PMID- 2254263 TI - Regulation of photolyase in Escherichia coli K-12 during adenine deprivation. AB - DNA photolyase, a DNA repair enzyme encoded by the phr gene of Escherichia coli, is normally regulated at 10 to 20 active molecules per cell. In purA mutants deprived of adenine, this amount increased sixfold within 2 h. Operon fusions placing lacZ under transcriptional control of phr promoters indicated no change in transcription rate during adenine deprivation, and gene fusions of phr with lacZ showed a nearly constant level of translation as well. Immunoblot analysis indicated that the total amount of photolyase protein remained constant during enzyme amplification. On the other hand, treatment of cells with chloramphenicol during the adenine deprivation prevented any increase. DNA regions lying 1.3 to 4.2 kb upstream of the phr coding sequences were necessary for this amplification to occur and for this purpose would function in trans. These results suggest that adenine deprivation leads to a posttranslational change, involving synthesis of protein encoded by sequences lying upstream of phr, which increases photolyase activity. The amplification in activity was found to be reversible, for when adenine was restored, the photolyase activity declined before cell growth resumed. PMID- 2254264 TI - Cloning, sequencing, and molecular analysis of the acetoacetate decarboxylase gene region from Clostridium acetobutylicum. AB - Acetoacetate decarboxylase (ADC) (EC4.1.1.4) of Clostridium acetobutylicum DSM 792 was purified to homogeneity, and its first 25 N-terminal amino acids were determined. Oligonucleotide probes deduced from this sequence were used to detect positive clones in partial gene banks derived from Sau3A and HaeIII digests with following ligation into the vector pUC9. In Escherichia coli, the 2.1-kbp HaeIII clones expressed high levels of ADC activity. The expression was independent of the orientation of the insert with respect to the lac promoter of the vector and also of the addition of isopropyl-beta-D-thiogalactopyranoside, thus indicating that sequences located on the clostridial DNA controlled transcription and translation. From the E. coli clone with the recombinant plasmid pUG93 containing the 2.1-kbp HaeIII fragment, the ADC protein was purified and compared with the native enzyme. Both were indistinguishable with respect to the molecular mass of subunits and native protein as well as to activity stain. The 2.9-kbp Sau3A fragment could be shown to contain the amino terminus of the acetoacetate decarboxylase (adc) gene but did not express enzyme activity. It partially overlapped with the HaeIII fragment, spanning together 4,053 bp of the clostridial genome that were completely sequenced. Four open reading frames (ORFs) could be detected, one of which was unambiguously assigned to the acetoacetate decarboxylase (adc) gene. Amino acid sequences of the N terminus and the catalytic center as deduced from the nucleotide sequence were identical to sequences obtained from direct analysis of the protein. Typical procaryotic transcriptional and translational start and stop signals could be found in the DNA sequence. Together with these regulatory sequences, the adc gene formed a single operon. The carboxyl terminus of the enzyme proved to be rather hydrophobic. In vitro transcription-translation assays resulted in formation of ADC and ORF3 gene product; the other two ORFs were not expressed. Whereas no homology of the adc gene and ORF2 could be detected with sequences available in the EMBL or GenBank data bases, the obviously truncated ORF1 showed significant similarity to alpha-amylase of Bacillus subtilis. The restriction pattern and N terminal amino acid sequence (as deduced from the nucleotide sequence) of ORF3 proved to be identical to those of the large subunit of acetoacetyl coenzyme A:acetate/butyrate:coenzyme A transferase. PMID- 2254265 TI - In vitro interactions of CysB protein with the cysK and cysJIH promoter regions of Salmonella typhimurium. AB - The cysteine regulons of Salmonella typhimurium and Escherichia coli are positively regulated by CysB protein and either O-acetyl-L-serine or N-acetyl-L serine, both of which act as inducers. Gel mobility shift assays and DNase I footprinting experiments showed that CysB protein binds to the S. typhimurium cysK promoter at two sites, one, designated CBS-K1, at positions -78 to -39 relative to the major transcription start site, and the other, designated CBS-K2, at positions -115 to -79. The S. typhimurium cysJIH promoter was found to contain a single binding site, designated CBS-JH, at positions -76 to -35. Acetyl-L serine stimulated binding to CBS-K1 and CBS-J and inhibited binding to CBS-K2. In the absence of acetyl-L-serine, CysB protein bound to both CBS-K1 and CBS-K2 and gave a complex that migrated more slowly during gel electrophoresis than did that formed in the presence of acetyl-L-serine, in which case CysB protein bound only to CBS-K1. Complexes formed with DNA containing the two binding sites either at the middle or at one end of the fragment migrated differently, suggesting that DNA was bent in the slow complex formed in the absence of acetyl-L-serine and that DNA in the fast complex was less bent or not bent at all. An analysis of upstream deletions of the cysK promoter showed that only CBS-K1 is required for in vivo promoter activity. CBS-J is analogous in position to CBS-K1 and is probably also required for activity of the cysJIH promoter. CBS-K2 has no known function but may help sequester CysB protein at the cysK promoter. PMID- 2254266 TI - Molecular cloning of the structural gene for exopolygalacturonate lyase from Erwinia chrysanthemi EC16 and characterization of the enzyme product. AB - The ability of Erwinia chrysanthemi to cause soft-rot diseases involving tissue maceration in many plants has been linked to the production of endo-pectate lyase E. chrysanthemi EC16 mutant UM1005, however, contains deletions in the pel genes that encode the known endopectate lyases, yet still macerates plant tissues. In an attempt to identify the remaining macerating factor(s), a gene library of UM1005 was constructed in Escherichia coli and screened for pectolytic activity. A clone (pPNL5) was identified in this library that contained the structural gene for an exopolygalacturonate lyase (ExoPL). The gene for ExoPL was localized on a 3.3-kb EcoRV fragment which contained an open reading frame for a 79,500-Da polypeptide. ExoPL was purified to apparent homogeneity from Escherichia coli DH5 alpha (pPNL5) and found to have an apparent molecular weight of 76,000 with an isoelectric point of 8.6. Purified ExoPL had optimal activity between pH 7.5 and 8.0 and could utilize pectate, citrus pectin, and highly methyl-esterified Link pectin as substrates. A PL- ExoPL- mutant of EC16 was constructed that exhibited reduced growth on pectate, but retained pathogenicity on chrysanthemum equivalent to that of UM1005. The results indicate that ExoPL does not contribute to the residual macerating activity of UM1005. PMID- 2254267 TI - Heat shock response of murine Chlamydia trachomatis. AB - We have investigated the heat shock response in the mouse pneumonitis strain of Chlamydia trachomatis. The kinetics of the chlamydial heat shock response resembled that of other procaryotes: the induction was rapid, occurring over a 5- to 10-min time period, and was regulated at the level of transcription. Immunoblot analysis and immunoprecipitations with heterologous antisera to the heat shock proteins DnaK and GroEL demonstrated that the rate of synthesis, but not the absolute amount of these two proteins, increased after heat shock. Using a general screen for genes whose mRNAs are induced by heat shock, we identified and cloned two of these. DNA sequence analysis demonstrated that one of the genes is a homolog of dnaK. Further sequence analysis of the region upstream of the dnaK gene revealed that the chlamydial homolog of the grpE gene is located just adjacent to the dnaK gene. The second locus encoded three potential nonoverlapping open reading frames. One of the open reading frames was 52% homologous to the ribosomal protein S18 of Escherichia coli and thus presumably encodes the chlamydial homolog. Interestingly, this ribosomal protein is not known to be induced by heat shock in E. coli. S1 nuclease and primer extension analyses located the start site of the dnaK transcript to the last nucleotide of the grpE coding sequence, suggesting that these two genes, although tandemly arranged, are transcribed separately. No promoter sequences resembling the E. coli consensus heat shock promoter could be identified upstream of either the C. trachomatis dnaK, grpE, or S18 gene. The induction of the dnaK and S18 mRNAs by heat shock occurred at a transcriptional level; their induction could be blocked by rifampin. The mechanisms of induction for these two loci were not the same, however; they were differentially sensitive to chloramphenicol. Whereas the induction of dnaK mRNA required de novo protein synthesis, the induction of the S18 mRNA did not. Thus, C. trachomatis utilizes at least two different pathways to induce the transcription of mRNAs encoding proteins induced in the heat shock response. PMID- 2254268 TI - Recombination at ColE1 cer requires the Escherichia coli xerC gene product, a member of the lambda integrase family of site-specific recombinases. AB - Site-specific recombination at the plasmid ColE1 cer site requires the Escherichia coli chromosomal gene xerC. The xerC gene has been localized to the 85-min region of the E. coli chromosome, between cya and uvrD. The nucleotide sequences of the xerC gene and flanking regions have been determined. The xerC gene encodes a protein with a calculated molecular mass of 33.8 kDa. This protein has substantial sequence similarity to the lambda integrase family of site specific recombinases and is probably the cer recombinase. The xerC gene is expressed as part of a multicistronic unit that includes the dapF gene and two other open reading frames. PMID- 2254269 TI - Characterization of cold-sensitive secY mutants of Escherichia coli. AB - Mutations which cause poor growth at a low temperature, which affect aspects of protein secretion, and which map in or around secY (prlA) were characterized. The prlA1012 mutant, previously shown to suppress a secA mutation, proved to have a wild-type secY gene, indicating that this mutation cannot be taken as genetic evidence for the secA-secY interaction. Two cold-sensitive mutants, the secY39 and secY40 mutants, which had been selected by their ability to enhance secA expression, contained single-amino-acid alterations in the same cytoplasmic domain of the SecY protein. Protein export in vivo was partially slowed down by the secY39 mutation at 37 to 39 degrees C, and the retardation was immediately and strikingly enhanced upon exposure to nonpermissive temperatures (15 to 23 degrees C). The rate of posttranslational translocation of the precursor to the OmpA protein (pro-OmpA protein) into wild-type membrane vesicles in vitro was only slightly affected by reaction temperatures ranging from 37 to 15 degrees C, and about 65% of OmpA was eventually sequestered at both temperatures. Membrane vesicles from the secY39 mutant were much less active in supporting pro-OmpA translocation even at 37 degrees C, at which about 20% sequestration was attained. At 15 degrees C, the activity of the mutant membrane decreased further. The rapid temperature response in vivo and the impaired in vitro translocation activity at low temperatures with the secY39 mutant support the notion that SecY, a membrane-embedded secretion factor, participates in protein translocation across the bacterial cytoplasmic membrane. PMID- 2254270 TI - Cloning and sequencing of a bile acid-inducible operon from Eubacterium sp. strain VPI 12708. AB - Two bile acid-inducible polypeptides from Eubacterium sp. strain VPI 12708 with molecular weights of 27,000 and approximately 45,000 have previously been shown to be encoded by genes residing on a 2.9-kb EcoRI fragment. We now report the cloning and sequencing of three additional overlapping DNA fragments upstream from this EcoRI fragment. Together, these four fragments contain a large segment of a bile acid-inducible operon which encodes the 27,000- and 45,000-Mr (now shown to be 47,500-Mr) polypeptides and open reading frames potentially coding for four additional polypeptides with molecular weights of 59,500, 58,000, 19,500, and 9,000 to 11,500. A bile acid-inducible polypeptide with an apparent Mr of 23,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was purified to homogeneity, and the N-terminal amino acid sequence that was obtained matched the sequence deduced from the open reading frame coding for the 19,500-Mr polypeptide. A short DNA segment containing the 3' downstream end of the gene coding for the 47,500-Mr polypeptide was not successfully cloned but was directly sequenced from DNA fragments synthesized by polymerase chain reaction. The mRNA initiation site for the bile acid-inducible operon was shown by primer extension to be immediately upstream from the gene encoding the 58,000-Mr polypeptide. A potential promoter region upstream from the mRNA initiation site displayed significant homology with the promoter regions of previously identified bile acid-inducible genes from Eubacterium sp. strain VPI 12708. We hypothesize that this bile acid-inducible operon codes for most of the enzymes involved in the bile acid 7 alpha-dehydroxylation pathway in this bacterium. PMID- 2254271 TI - Cloning, sequencing, and regulation of expression of an extracellular esterase gene from the plant pathogen Streptomyces scabies. AB - The gene that encodes the extracellular esterase produced by Streptomyces scabies has been cloned and sequenced. The gene was identified by hybridization to a synthetic oligonucleotide that corresponds to the amino-terminal amino acid sequence determined for the secreted form of the esterase. Nucleotide sequence analysis predicted a 345-amino-acid open reading frame, a putative ribosome binding site, and 39 amino acids at the amino terminus of the sequence that is not found in the secreted protein. This 39-amino-acid sequence has many of the characteristics common to known signal peptides. End mapping the esterase transcript revealed a single 5' end of the mRNA located 51 nucleotides upstream from the start point for translation. Northern (RNA) hybridization analysis of the esterase message by using the cloned esterase gene as a probe indicated that the esterase mRNA is about 1,440 nucleotides in length and was detected only when the cells were grown in the presence of zinc. These results suggest that the level of esterase mRNA detected in the cells is regulated by zinc. PMID- 2254272 TI - Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD). AB - We have characterized two genes of the Escherichia coli K-12 gab cluster, which encodes the enzymes of the 4-aminobutyrate degradation pathway. The nucleotide sequence of gabT, coding for glutamate:succinic semialdehyde transaminase (EC 2.6.1.19), alternatively known as 4-aminobutyrate transaminase, was determined. The structural gene consists of 1,281 nucleotides specifying a protein of 426 amino acids with a molecular mass of 45.76 kDa. The protein shows significant homologies to the ornithine transaminases from Saccharomyces cerevisiae and from rat and human mitochondria. Three functionally and structurally important amino acid residues of the transaminase were identified by sequence comparison studies, and evolutionary relationships of the aminotransferases are discussed. The gabD gene, encoding succinic semialdehyde dehydrogenase (EC 1.2.1.16), was cloned and shown to be located adjacent to the 5' end of gabT. Expression studies with subfragments of the initially cloned DNA region revealed a maximal size of 1.7 kb for gabD. Both genes are cotranscribed from a promoter located upstream of gabD. PMID- 2254273 TI - Cloning of the Klebsiella aerogenes nac gene, which encodes a factor required for nitrogen regulation of the histidine utilization (hut) operons in Salmonella typhimurium. AB - The nac (nitrogen assimilation control) gene from Klebsiella aerogenes, cloned in a low-copy-number cloning vector, restored the ability of K. aerogenes nac mutants to activate histidase and repress glutamate dehydrogenase formation in response to nitrogen limitation and to limit the maximum expression of the nac promoter. When present in Salmonella typhimurium, the K. aerogenes nac gene allowed the hut genes to be activated during nitrogen-limited growth. Thus, the nac gene encodes a cytoplasmic factor required for activation of hut expression in S. typhimurium during nitrogen-limited growth. PMID- 2254274 TI - Nitrate- and molybdenum-independent signal transduction mutations in narX that alter regulation of anaerobic respiratory genes in Escherichia coli. AB - Escherichia coli can respire anaerobically by reducing nitrate, trimethylamine-N oxide, dimethyl sulfoxide, or fumarate. When nitrate is present, expression of the genes for fumarate (frdABCD), trimethylamine-N-oxide, and dimethyl sulfoxide (dmsABC) is repressed while expression of the nitrate reductase (narGHJI) gene is induced. This regulation requires molybdate and is mediated by the narX and narL gene products, which together form a two-component regulatory system. We provide evidence that NarX is a nitrate and molybdenum sensor which activates NarL when nitrate is available to cells. Mutants generated by hydroxylamine mutagenesis were repressed for frdA-lacZ expression even when cells were grown in the absence of nitrate. The mutations responsible for three of these nitrate independence (NarX*) phenotypes were localized to narX and further characterized in vivo for their ability to repress frdA-lacZ expression. Two of the mutants (the narX64 and narX71 mutants) had a greatly reduced requirement for molybdenum to function but still responded to nitrate. In contrast, a third mutant (the narX32 mutant) required molybdenum but did not exhibit full repression of frdA-lacZ expression even when nitrate was present. These narX* alleles also caused the induction of nitrate reductase gene expression and the repression of a dmsA-lacZ fusion in the absence of nitrate. Each narX* mutation was determined to lie in an 11-amino-acid region of the NarX polypeptide that follows a proposed transmembrane domain. We suggest that the conformation of the narX* gene products is altered such that even in the absence of nitrate each of these gene products more closely resembles the wild-type NarX protein when nitrate is present. These data establish a clear role for the narX gene product in gene regulation and strongly suggest its role in sensing nitrate and molybdenum. PMID- 2254275 TI - Cloning and sequence of the Salmonella typhimurium hemL gene and identification of the missing enzyme in hemL mutants as glutamate-1-semialdehyde aminotransferase. AB - Salmonella typhimurium forms the heme precursor delta-aminolevulinic acid (ALA) exclusively from glutamate via the five-carbon pathway, which also occurs in plants and some bacteria including Escherichia coli, rather than by ALA synthase catalyzed condensation of glycine and succinyl-coenzyme A, which occurs in yeasts, fungi, animal cells, and some bacteria including Bradyrhizobium japonicum and Rhodobacter capsulatus. ALA-auxotrophic hemL mutant S. typhimurium cells are deficient in glutamate-1-semialdehyde (GSA) aminotransferase, the enzyme that catalyzes the last step of ALA synthesis via the five-carbon pathway. hemL cells transformed with a plasmid containing the S. typhimurium hemL gene did not require ALA for growth and had GSA aminotransferase activity. Growth in the presence of ALA did not appreciably affect the level of extractable GSA aminotransferase activity in wild-type cells or in hemL cells transformed with the hemL plasmid. These results indicate that GSA aminotransferase activity is required for in vivo ALA biosynthesis from glutamate. In contrast, extracts of both wild-type and hemL cells had gamma,delta-dioxovalerate aminotransferase activity, which indicates that this reaction is not catalyzed by GSA aminotransferase and that the enzyme is not encoded by the hemL gene. The S. typhimurium hemL gene was sequenced and determined to contain an open reading frame of 426 codons encoding a 45.3-kDa polypeptide. The sequence of the hemL gene bears no recognizable similarity to the hemA gene of S. typhimurium or E. coli, which encodes glutamyl-tRNA reductase, or to the hemA genes of B. japonicum or R. capsulatus, which encode ALA synthase. The predicted hemL gene product does show greater than 50% identity to barley GSA aminotransferase over its entire length. Sequence similarity to other aminotransferases was also detected. PMID- 2254276 TI - Saturation and specificity of the Lon protease of Escherichia coli. AB - Lon is an ATP-dependent protease of Escherichia coli. The lon mutation has a pleiotropic phenotype: UV sensitivity, mucoidy, deficiency for lysogenization by bacteriophage lambda and P1, and lower efficiency in the degradation of abnormal proteins. All of these phenotypes are correlated with the loss of protease activity. Here we examine the effects of overproduction of one Lon substrate, SulA, and show that it protects two other substrates from degradation. To better understand this protection, we mutagenized the sulA gene and selected for mutants that have partially or totally lost their ability to saturate the Lon protease and thus can no longer protect another substrate. Some of the SulA mutants lost their ability to protect RcsA from degradation but could still protect the O thermosensitive mutant protein (Ots). All of the mutants retained their capacity to induce cell division inhibition. It was also found that deletion of the C terminal end of SulA affected its activity but did not affect its susceptibility to Lon. We propose that Lon may have more than one specificity for peptide cleavage. PMID- 2254277 TI - A negatively charged N terminus in the alpha polypeptide inhibits formation of light-harvesting complex I in Rhodobacter capsulatus. AB - Light-harvesting complex I (LHI) of Rhodobacter capsulatus contains bacteriochlorophyll and carotenoids which are noncovalently bound to two different apoproteins (alpha and beta polypeptides) carrying oppositely charged N terminal ends. The contribution of these charged segments to the assembly of LHI was studied with mutants having oppositely charged amino acids in the alpha or beta polypeptide. The influence of these mutations on the insertion and assembly process of the LHI complex was investigated by means of spectroscopic analysis of isolated intracytoplasmic membranes and pulse-chase experiments. Exchange of four positively charged amino acids to negatively charged amino acids on the N terminal domain of the alpha subunit inhibited completely the assembly of the LHI complex. Although this mutant has no antenna, the reaction center is active and the cells were able to grow anaerobically in the light. Conversely, mutation of the four negatively charged amino acids of the N-terminal segment of the beta polypeptide did not prevent the assembly of the LHI complex, although the stability of the complex and the size of the photosynthetic unit were affected. The presence of the mutated beta polypeptide was confirmed by protein sequencing. PMID- 2254278 TI - Role of Escherichia coli heat shock proteins DnaK and HtpG (C62.5) in response to nutritional deprivation. AB - Because of the highly conserved pattern of expression of the eucaryotic heat shock genes hsp70 and hsp84 or their cognates during sporulation in Saccharomyces cerevisiae and development in higher organisms, the role of the Escherichia coli homologs dnaK and htpG was examined during the response to starvation. The htpG deletion mutant was found to be similar to its wild-type parent in its ability to survive starvation for essential nutrients and to induce proteins specific to starvation conditions. The dnaK103 mutant, however, was highly susceptible to killing by starvation for carbon and, to a lesser extent, for nitrogen and phosphate. Analysis of proteins induced under starvation conditions on two dimensional gels showed that the dnaK103 mutant was defective for the synthesis of some proteins induced in wild-type cells by carbon starvation and of some proteins induced under all starvation conditions, including the stationary phase in wild-type cells. In addition, unique proteins were synthesized in the dnaK103 mutant in response to starvation. Although the synthesis of some proteins under glucose starvation control was drastically affected by the dnaK103 mutation, the synthesis of proteins specifically induced by nitrogen starvation was essentially unaffected. Similarly, the dnaK103 mutant was able to grow, utilizing glutamine or arginine as a source of nitrogen, at a rate approximate to that of the wild type parent, but it inefficiently utilized glycerol or maltose as carbon sources. Several differences between the protein synthetic pattern of the dnaK103 mutant and the wild type were observed after phosphate starvation, but these did not result in a decreased ability to survive phosphate starvation, compared with nitrogen starvation. PMID- 2254279 TI - Nucleotide sequence of the fruA gene, encoding the fructose permease of the Rhodobacter capsulatus phosphotransferase system, and analyses of the deduced protein sequence. AB - The nucleotide sequence of the fruA gene, the terminal gene in the fructose operon of Rhodobacter capsulatus, is reported. This gene codes for the fructose permease (molecular weight, 58,575; 578 aminoacyl residues), the fructose enzyme II (IIFru) of the phosphoenolpyruvate-dependent phosphotransferase system. The deduced aminoacyl sequence of the encoded gene product was found to be 55% identical throughout most of its length with the fructose enzyme II of Escherichia coli, with some regions strongly conserved and others weakly conserved. Sequence comparisons revealed that the first 100 aminoacyl residues of both enzymes II were homologous to the second 100 residues, suggesting that an intragenic duplication of about 300 nucleotides had occurred during the evolution of IIFru prior to divergence of the E. coli and R. capsulatus genes. The protein contains only two cysteyl residues, and only one of these residues is conserved between the two proteins. This residue is therefore presumed to provide the active-site thiol group which may serve as the phosphorylation site. IIFru was found to exhibit regions of homology with sequenced enzymes II from other bacteria, including those specific for sucrose, beta-glucosides, mannitol, glucose, N-acetylglucosamine, and lactose. The degree of evolutionary divergence differed for different parts of the proteins, with certain transmembrane segments exhibiting high degrees of conservation. The hydrophobic domain of IIFru was also found to be similar to several uniport and antiport transporters of animals, including the human and mouse insulin-responsive glucose facilitators. These observations suggest that the mechanism of transmembrane transport may be similar for permeases catalyzing group translocation and facilitated diffusion. PMID- 2254280 TI - Effects of glutamines and glutamates at sites of covalent modification of a methyl-accepting transducer. AB - Chemotactic transducer proteins of Escherichia coli contain four or five methyl accepting glutamates that are crucial for sensory adaptation and gradient sensing. Two residues arise from posttranslational deamidation of glutamines to yield methyl-accepting glutamates. We addressed the significance of this arrangement by creating two mutated trg genes: trg(5E), coding for a transducer in which all five modification sites were synthesized as glutamates, and trg(5Q), in which all five were glutamines. We found that the normal (3E,2Q) configuration was not an absolute requirement for synthesis, assembly, or stable maintenance of transducers. Both mutant proteins were methylated, although Trg(5Q) had a reduced number of methyl-accepting sites because two glutamines at adjacent residues were blocked for deamidation and thus could not become methyl-accepting glutamates. The glutamine-glutamate balance had striking effects on signaling state. Trg(5E) was in a strong counterclockwise signaling configuration, and Trg(5Q) was in a strong clockwise signaling induced by ligand binding, and alanines substituted at modification sites had an intermediate effect. Chemotactic migration by growing cells containing trg(5E) or trg(5Q) exhibited reduced effectiveness, probably reflecting perturbations of the counterclockwise/clockwise ratio caused by newly synthesized transducers not modified rapidly enough to produce a balanced signaling state during growth. These defects were evident for cells in which other transducers were not available to contribute to balanced signaling or were present at lower levels than the mutant proteins. PMID- 2254281 TI - Role of purine biosynthetic intermediates in response to folate stress in Escherichia coli. AB - Folic acid plays a central role in anabolic metabolism by supplying single-carbon units at varied levels of oxidation for both nucleotide and amino acid biosyntheses. It has been proposed that 5-amino-4-imidazole carboxamide riboside 5'-triphosphate (ZTP), an intermediate in de novo purine biosynthesis, serves as a signal of cellular folate stress and mediates a physiologically beneficial response to folate stress in Salmonella typhimurium (B. R. Bochner, and B. N. Ames, Cell 29:929-937, 1982). We examined the physiological response of Escherichia coli to folate stress induced by the drugs psicofuranine, trimethoprim, and sodium sulfathiazole or by p-aminobenzoic acid (pABA) starvation. Analysis of nucleotide pools showed that psicofuranine or trimethoprim treatment of a prototrophic strain or growth of a pABA auxotroph on limiting pABA induced the production of the nucleotide ZTP, as previously observed in S. typhimurium by Bochner and Ames. Accumulation of ZTP and its precursor 5-amino-4-imidazole carboxamide riboside 5'-monophosphate (ZMP) did not correlate well with folate stress in E. coli, as measured by determination of the folate/protein ratios of extracts of treated cells. Treatment of cells with psicofuranine caused a marked accumulation of 5-amino-4-imidazole carboxamide ribonucleotides (Z-ribonucleotides) but a statistically insignificant drop in the folate/protein ratio of cell extracts. Sodium sulfathiazole treatment at a drug concentration that led to a threefold drop in the growth rate and in the folate/protein ratio of treated cells led to little accumulation of Z ribonucleotides in E. coli A purF his+ strain which produces ZTP and ZMP when treated with trimethoprim was constructed. In this strain, histidine represses the synthesis of both ZMP and ZTP. Treatment of cells of this strain with trimethoprim resulted in a decrease in the folate/protein ratio of cell extracts, but a blockade of Z-ribonucleotide accumulation did not affect the extent of folate depletion seen in treated cells and had only a small effect on the resistance of this strain to growth inhibition by trimethoprim. The patterns of protein expression induced by treatment of this strain with trimethoprim or psicofuranine were examined by two-dimensional electrophoretic resolution of the total cellular proteins. No differences in protein expression were seen when the treatment were performed in media containing or lacking histidine. These studies failed to provide evidence in E. coli for a folate stress regulon controlled by ZTP. PMID- 2254283 TI - Regulation of assimilatory nitrate reductase formation in Klebsiella aerogenes W70. AB - Klebsiella aerogenes W70 could grow aerobically with nitrate or nitrite as the sole nitrogen source. The assimilatory nitrate reductase and nitrite reductase responsible for this ability required the presence of either nitrate or nitrite as an inducer, and both enzymes were repressed by ammonia. The repression by ammonia, which required the NTR (nitrogen regulatory) system (A. Macaluso, E. A. Best, and R. A. Bender, J. Bacteriol. 172:7249-7255, 1990), did not act solely at the level of inducer exclusion, since strains in which the expression of assimilatory nitrate reductase and nitrite reductase was was independent of the inducer were also susceptible to repression by ammonia. Insertion mutations in two distinct genes, neither of which affected the NTR system, resulted in the loss of both assimilatory nitrate reductase and nitrite reductase. One of these mutants reverted to the wild type, but the other yielded pseudorevertants at high frequency that were independent of inducer but still responded to ammonia repression. PMID- 2254282 TI - Sequence and genetic organization of a Zymomonas mobilis gene cluster that encodes several enzymes of glucose metabolism. AB - The Zymomonas mobilis genes that encode glucose-6-phosphate dehydrogenase (zwf), 6-phosphogluconate dehydratase (edd), and glucokinase (glk) were cloned independently by genetic complementation of specific defects in Escherichia coli metabolism. The identity of these cloned genes was confirmed by various biochemical means. Nucleotide sequence analysis established that these three genes are clustered on the genome and revealed an additional open reading frame in this region that has significant amino acid identity to the E. coli xylose proton symporter and the human glucose transporter. On the basis of this evidence and structural analysis of the deduced primary amino acid sequence, this gene is believed to encode the Z. mobilis glucose-facilitated diffusion protein, glf. The four genes in the 6-kb cluster are organized in the order glf, zwf, edd, glk. The glf and zwf genes are separated by 146 bp. The zwf and edd genes overlap by 8 bp, and their expression may be translationally coupled. The edd and glk genes are separated by 203 bp. The glk gene is followed by tandem transcriptional terminators. The four genes appear to be organized in an operon. Such an arrangement of the genes that govern glucose uptake and the first three steps of the Entner-Doudoroff glycolytic pathway provides the organism with a mechanism for carefully regulating the levels of the enzymes that control carbon flux into the pathway. PMID- 2254284 TI - Genomic maps of some strains within the Mycoplasma mycoides cluster. AB - Genomic restriction maps for the small colony (SC) strains (PG1, KH3J, Gladysdale, and V5) of Mycoplasma mycoides subsp. mycoides (the agent of contagious bovine pleuropneumonia) and for Mycoplasma strain PG50 (classified as bovine serogroup 7), with respective sizes of 1,280, 1,280, 1,260, 1,230, and 1,040 kbp, were compared with the map (1,200 kbp) for a large colony strain (Y goat) of M. mycoides subsp. mycoides. The number and order of all mapped restriction sites were fully conserved in the SC genomes, as were the approximate positions of mapped loci. A number of these restriction sites in the Y genome and some, but fewer, in the PG50 genome appeared to be conserved. The SC and large colony strains shared conservation in the relative positions of the mapped loci, except for rpoC. PMID- 2254285 TI - Purification and partial characterization of delta-(L-alpha-aminoadipyl)-L cysteinyl-D-valine synthetase from Streptomyces clavuligerus. AB - delta-(L-alpha-Aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) was purified from Streptomyces clavuligerus by a combination of salt precipitation, ultrafiltration, and anion-exchange chromatography. The final purified material gave two protein bands with molecular weights of 283,000 and 32,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoresis in nondenaturing gels gave a single protein band with an estimated molecular weight of 560,000. These results suggest that ACVS is a multimer composed of nonidentical subunits. PMID- 2254286 TI - Mechanism of enzymatic dehalogenation of pentachlorophenol by Arthrobacter sp. strain ATCC 33790. AB - Pentachlorophenol (PCP) dehalogenase from Arthrobacter sp. strain ATCC 33790 converts PCP to tetrachlorohydroquinone. In labeling experiments with H(2)18O or 18O2, only with H(2)18O was labeled product found. However, unlabeled tetrachlorohydroquinone became labeled after incubation with the enzyme in H(2)18O. Therefore, distinction between an oxygenolytic or a hydrolytic dehalogenation mechanism for the PCP dehalogenase is not possible. PMID- 2254287 TI - DNA sequences required for the alkalophily of Bacillus sp. strain C-125 are located close together on its chromosomal DNA. AB - Two alkali-sensitive mutants of alkalophilic Bacillus sp. strain C-125 were obtained. Mutant 38154 showed defective regulation of internal pH. Plasmids pALK1 and pALK2, containing DNA fragments different from those of the parent strain, were able to recover alkalophily in mutants 18224 and 38154, respectively. DNA analysis suggested that the two fragments overlapped on the chromosomal DNA of strain C-125. PMID- 2254288 TI - The nucleotide sequence of the Desulfovibrio gigas desulforedoxin gene indicates that the Desulfovibrio vulgaris rbo gene originated from a gene fusion event. AB - Expression of the rbo gene from Desulfovibrio vulgaris Hildenborough in Escherichia coli minicells and Western blotting (immunoblotting) of Desulfovibrio cell extracts with antibodies raised against a synthetic peptide indicated the presence of a 14-kDa polypeptide product, as expected from the gene sequence. Cloning and sequencing of the gene (dsr) for desulforedoxin, a 4-kDa redox protein from Desulfovibrio gigas, showed that it is formed by expression of an autonomous gene of 111 bp, not by processing of a 14-kDa protein. The results indicate that the rbo gene product, which has a 4-kDa desulforedoxin domain as the NH2 terminus, may have arisen by gene fusion. Shuffling and fusion of genes for redox protein domains can explain the large variety of redox proteins found in sulfate-reducing bacteria. PMID- 2254289 TI - Proteolysis and modulation of the activity of the cell division inhibitor SulA in Escherichia coli lon mutants. AB - Intracellular accumulation of the inducible cell division inhibitor SulA is modulated by proteases that ensure its degradation, namely, the Lon protease and another ATP-dependent protease(s). Lon- cells are UV sensitive because SulA is stable. We asked whether these ATP-dependent proteases are more active when lon cells are grown at high temperature or in synthetic medium since these conditions decrease the UV sensitivity of lon cells. We found that these growth conditions have no direct effect on Lon-independent degradation of SulA. They may, instead, decrease the SulA-FtsZ interaction. PMID- 2254290 TI - Alveolysin, the thiol-activated toxin of Bacillus alvei, is homologous to listeriolysin O, perfringolysin O, pneumolysin, and streptolysin O and contains a single cysteine. AB - The gene coding for alveolysin, the thiol-activated toxin produced by Bacillus alvei, has been cloned by means of an oligonucleotide based on the known N terminal sequence of the secreted protein. The complete nucleotide sequence of the gene has been determined. The deduced amino acid sequence of alveolysin shows that alveolysin shares homologies with listeriolysin O, perfringolysin O, pneumolysin, and streptolysin O. Alveolysin, like the other members of the family, contains a single cysteine in the conserved peptide sequence ECTGLA WEWWR. PMID- 2254292 TI - [Salivary pH and lysozyme during oropharyngeal radiotherapy]. AB - The pH and lysozyme content of the salivas of 34 patients receiving radiotherapy of the upper respiratory digestive tracts for the treatment of cancer were compared to those of 22 healthy subjects matched for age and gender. After irradiation the salivas of the treated patients had a lower mean pH (p less than 0.001). During radiotherapy no statistically significant changes occurred in the pH or lysozyme rate, but at the beginning of treatment there was an inverse correlation (p less than 0.05) between the increased lysozyme content and the lowered pH. The mean salivary pH and lysozyme rate of 12 patients (35%) initially treated by chemotherapy showed no significant differences from controls. However, the saliva of 21 dentate patients had a mean pH and lysozyme content considerably higher (p less than 0.01) than that of patients without teeth. During radiotherapy there was a statistically significant inverse relationship between the pH of the salivas of the dentate and edentulous groups. PMID- 2254291 TI - Isolation and characterization of Bacillus stearothermophilus 30S and 50S ribosomal protein mutations. AB - Bacillus stearothermophilus mutations which confer resistance to or dependence on a variety of ribosome-targeted antibiotics have been isolated. Many of these mutations produce ribosomal proteins with altered mobilities in a two-dimensional gel electrophoresis system. This collection of altered thermophilic ribosomal proteins will be useful in examining ribosomal structure and function. PMID- 2254293 TI - Molecular changes during determination and differentiation of the dental mesenchymal cell lineage. AB - The lineage of dental mesenchymal cells originates in the cranial neural crest, and after sequential determination and differentiation, gives rise to all structures of the tooth and its supporting tissues, except the enamel. Reciprocal interactions between the epithelial and mesenchymal tissues are conceivably the most important regulators of dental mesenchymal cell differentiation. The molecular mechanisms of this epigenetic regulation are not known at present. In order to examine the mechanisms of regulation of gene expression in the lineage of dental mesenchymal cells, information is needed on the molecular changes that accompany advancing differentiation. By using the molar tooth germ of mouse embryos as a model system, the changes in the expression of some molecules have been analysed by immunohistological localization and in situ hybridization, and the roles of tissue interactions in this process examined. This has shown that syndecan, a recently characterized cell surface proteoglycan, and tenascin, a matrix glycoprotein, appear in the condensing dental mesenchyme during the bud stage of tooth development. During the cap stage, dental mesenchyme is characterized by continued intense expression of syndecan, but this is lost during terminal differentiation of odontoblasts. Tenascin and syndecan may mediate cell-matrix interactions during condensation of dental mesenchymal cells. Expression of the Int-2 proto-oncogene, coding for a fibroblast growth factor related molecule, can be detected by in situ hybridization in dental mesenchyme at the cap stage. This expression persists in cuspal mesenchyme at the bell stage but is lost from odontoblasts and from pulpal mesenchyme at progressive stages of tooth development. The advancement of tooth morphogenesis from cap to bell stage is accompanied by expression of alkaline phosphatase in the cuspal mesenchyme. Also tenascin, which is only weakly expressed during the cap stage, appears in the cuspal areas and shows codistribution with alkaline phosphatase. These observations indicate that the sequential determination and differentiation of the dental mesenchymal cells are characterized by a cascade of specific molecular changes. The cell surface proteoglycan syndecan and the Int-2 proto-oncogene are specific and transient markers of early dental mesenchymal cell differentiation. This information allows studies on the mechanisms of developmental regulation. These experimental tissue recombination studies indicate that the expression of syndecan and tenascin in the early dental mesenchyme is induced by the presumptive dental epithelium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254294 TI - Molecular conformation of porcine amelogenins and its significance in protein mineral interaction: 1H-NMR photo-CIDNP study. AB - The present 1H-nmr study was undertaken to investigate the molecular structure of porcine amelogenins in solution using photo-CIDNP (chemically induced dynamic nuclear polarization). The proteins of interest were the parent 25 kD amelogenin consisting of 173 amino acid residues and its degraded products having molecular masses of 23 kD, 20 kD, 13 kD and 5 kD on SDS-PAGE. From the recorded 1H-nmr and photo-CIDNP spectra, it was found that: 1) the Trp161 at the C-terminus of the 25 kD protein showed a stronger photo-CIDNP effect than the other two Trp25,45 at the N-terminus; 2) Tyr residues at the N-terminus of the 25 kD and 20 kD amelogenins gave rise to the strong peak around 6.8 ppm, indicating that at least some of the six Tyr residues are surface residues; and 3) the accessibility of His residues was quite different between the 13 kD fragment and the 25 kD and 20 kD proteins. These results suggest that the hydrophilic segment at the C-terminus is most likely exposed on the molecular surface and that the molecular structure of the amelogenin in solution may change substantially by the cleavage of the segments at the N- and C-termini. PMID- 2254295 TI - The possible role of alkaline phosphatase in acellular cementum formation. PMID- 2254296 TI - The development of the periodontal ligament with special reference to collagen fibre ontogeny. AB - The development of the periodontal ligament was investigated from serial sections of the mandibles of ferrets ranging in age from 42 days to 66 days post partum. Both succedaneous and non-succedaneous teeth were studied and similarities were seen in both types of tooth. No significant amounts of alveolar bone were observed being deposited beneath the erupting root apices and periodontal collagen fibres were seen attached to the walls of the sockets just prior to emergence of the crown into the oral cavity. Compared with the condition a few days after eruption, the collagen fibres on, and just prior to, emergence were thinner, had a more limited area of attachment, and were more randomly orientated. The results indicate that alveolar bone deposition and collagen traction do not generate the eruptive force and that there are species differences in these structural features during the eruptive process. PMID- 2254297 TI - Shark tooth morphogenesis. An SEM and EDX analysis of enameloid and dentin development in various shark species. AB - The study provides a survey of shark tooth morphogenesis based on SEM and EDX analyses of whole tooth families in six shark species. The teeth, demonstrating different stages of development, were acid-etched and coated with palladium. Calcium content was determined semi-quantitatively by using the palladium coating as an internal standard. Due to the rapid development of the enameloid, all major events took place in the two or three youngest teeth of a tooth family. Enameloid appeared to develop as a transformation of the peripheral part of the dental papilla. Mineralization started immediately. Based on morphological criteria the middle zone of the enameloid was established at an early stage, excluding the possibility of an unambiguous centrifugal or centripetal direction of growth. Substantial mineral increase first occurred in the middle zone, spreading from the tooth tip toward the base. Dentin formed after the enameloid was completely established. Dentin formation started basally as a direct prolongation of the enameloid cap, then spreading toward the tooth tip, first along the edges. It is concluded that shark enameloid has a mesenchymal background, but a role played by the inner dental epithelium can not be excluded. PMID- 2254298 TI - Transforming growth factor-alpha. A model for membrane-anchored growth factors. PMID- 2254299 TI - Structural and functional reconstitution of the glucocorticoid receptor-hsp90 complex. AB - Untransformed steroid receptors in cytosol preparations are associated with the 90-kDa heat shock protein hsp90, but the study of how hsp90 affects receptor function has been held back by the inability to reassociate steroid receptors with hsp90 in cell-free systems. Recently we showed (Dalman, F.C., Bresnick, E. H., Patel, P. D., Perdew, G. H., Watson, S. J., and Pratt, W. B. (1989) J. Biol. Chem. 264, 19815-19821) that glucocorticoid receptors translated in rabbit reticulocyte lysate bind to hsp90 at the termination of receptor translation. In this work we show that rabbit reticulocyte lysate promotes the temperature dependent association of hsp90 with immunopurified mouse L cell glucocorticoid receptors. Reticulocyte lysate also promotes the temperature-dependent dissociation of hormone-free receptors from a prebound receptor-DNA complex. The glucocorticoid receptor is released from DNA in association with rabbit hsp90, and reconstitution of the receptor-hsp90 complex is accompanied by complete restitution of steroid binding activity and repression of DNA binding activity. This is the first time that transformation of a DNA-bound steroid receptor has been reversed and it raises the question of whether the same or a similar system is involved in the termination of transcriptional activation when steroid dissociates from DNA-bound receptors in intact cells. PMID- 2254300 TI - Characterization of the apolipoprotein B mRNA editing activity in enterocyte extracts. AB - Apolipoprotein B (apoB) circulates in human plasma as two isoforms, apoB-100 (512 kDa) and apoB-48 (242 kDa). ApoB-48 is generated by a novel RNA editing mechanism which post-transcriptionally modifies apoB mRNA in the intestine by converting cytidine at nucleotide 6666 to uridine. This converts codon 2153 from glutamine (CAA) to a premature stop codon (UAA). To characterize the activity which edits apoB mRNA, extracts were prepared from enterocytes isolated from baboon small intestine. These extracts efficiently edit synthetic apoB RNA in vitro. Editing was detected by primer extension, and the specificity of the reaction was confirmed by DNA sequencing. Extracts prepared from other baboon tissues did not edit apoB RNA in vitro. The editing activity was partially purified by chromatography of the enterocyte extracts on DEAE-cellulose. The activity is sensitive to proteinase K but resistant to micrococcal nuclease and has an average molecular mass of 125 kDa when analyzed by gel filtration chromatography. PMID- 2254301 TI - Iron (III) hydroxamate transport into Escherichia coli. Substrate binding to the periplasmic FhuD protein. AB - Due to its extreme insolubility, Fe3+ is not transported as a monoatomic ion. In microbes, iron is bound to low molecular weight carriers, designated siderophores. For uptake into cells of Escherichia coli Fe3+ siderophores have to be translocated across two membranes. Transport across the outer membrane is receptor-dependent and energy-coupled; transport across the cytoplasmic membrane seems to follow a periplasmic binding protein-dependent transport mechanism. In support of this notion we demonstrate specific binding of the Fe3+ hydroxamate compounds ferrichrome, aerobactin, and coprogen, which are transported via the Fhu system, to the periplasmic FhuD protein, and no binding of the transport inactive ferrichrome A, ferric citrate, and iron sulfate. About 10(4) ferrichrome molecules were bound to the FhuD protein of cells which overproduced plasmid encoded FhuD. Binding depended on transport across the outer membrane mediated by the FhuA receptor and the TonB protein. Binding to FhuD was supported by the exclusive resistance of FhuD to proteinase K in the presence of the transport active hydroxamates. The overproduced precursor form of the FhuD protein was not protected by the Fe3+ hydroxamates indicating a conformation different to the mature form. The FhuD protein apparently serves as a periplasmic carrier for Fe3+ hydroxamates with widely different structures. PMID- 2254302 TI - Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. AB - The lutropin-choriogonadotropin (LH/CG) receptor is a cell surface receptor comprised of two domains of roughly equivalent size. The amino-terminal half of the receptor is relatively hydrophilic and is located extracellularly, whereas the carboxyl-terminal half of the receptor shares amino acid homology with other receptors that couple to G proteins and is similarly thought to span the plasma membrane seven times, ending with a relatively short carboxyl-terminal tail. In order to test the role of the extracellular domain in binding hormone, we constructed a mutated rat luteal LH/CG receptor cDNA (termed pCLHR-D2), which encodes for only the extracellular domain, and used it to transiently transfect human kidney 293 cells. Here we report that the expressed extracellular domain of the LH/CG receptor is capable of binding human CG with a high affinity, comparable with that of the full-length receptor. Thus, not only is the extracellular domain of the glycoprotein hormone receptors involved in binding hormone, but it alone is capable of conferring high affinity binding. Unexpectedly, it was also found that this truncated receptor is not secreted into the culture media but remains trapped within the cells. PMID- 2254303 TI - Isozyme specificity in the conversion of hepoxilin A3 (HxA3) into a glutathionyl hepoxilin (HxA3-C) by the Yb2 subunit of rat liver glutathione S-transferase. AB - 1-14C-Labeled hepoxillin A3 is transformed by a purified preparation of glutathione S-transferase in the presence of glutathione into a glutathionyl conjugate in which the glutathione is covalently coupled to the carbon 11 position of hepoxilin A3. We have termed the glutathione conjugate hepoxilin A3-C in keeping with the established nomenclature for glutathione conjugates in the leukotriene series. Using [3H]glutathione as cosubstrate, the kinetics of the reaction were followed. Among various rat liver glutathione S-transferase isozymes, a homodimer of the Yb2 subunit showed the best activity, while isozymes containing the Ya and Yc subunits showed marginal activity with hepoxilin A3 as substrate. PMID- 2254304 TI - The transcription factor LAC9 from Kluyveromyces lactis-like GAL4 from Saccharomyces cerevisiae forms a Zn(II)2Cys6 binuclear cluster. AB - The DNA binding domain of the transcription factor LAC9 contains 6 cysteine residues with spacing in the primary peptide sequence identical to that found in the DNA binding domain of the GAL4 transcription factor. In GAL4, the CysX2CysX6CysX6CysX2CysX6Cys motif has been shown to form a Zn(II)2Cys6 binuclear cluster (Pan, T. and Coleman, J. E. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 2077-2081), representing a new structure for a Zn(II)-containing transcription factor which differs from the "zinc finger" motif first described for TFIIIA. LAC9 has been shown to bind two Zn(II) ions (Halvorsen, Y. C., Nandabalan, K., and Dickson, R. D. (1990) J. Biol. Chem. 265, 13283-13289). The similarity of the amino acid sequence and the Cys spacing within the DNA binding domain suggest that LAC9 should also be capable of forming the Zn(II)2Cys6 cluster found in GAL4. A fragment of LAC9 consisting of 144 amino acid residues spanning the DNA binding domain has been prepared with 113Cd(II) substituted for the two native Zn(II) ions. 113Cd NMR of this fragment (denoted LAC9(85-228*] has been carried out in an attempt to test the hypothesis that LAC9, like GAL4, forms a binuclear cluster. The chemical shifts of the two bound 113Cd(II) ions, 705 and 692 ppm respectively, are consistent with ligation of each 113Cd(II) ion to 4 sulfur atoms. The best model for such ligation is that two of the cysteine S- form bridges between the two Cd(II) ions. Formation of a Zn(II)-Cd(II) hybrid form of LAC9(85-228*) has also been observed. We conclude that LAC9 contains a Zn(II)2Cys6 binuclear cluster as previously reported for GAL4. PMID- 2254305 TI - Single crystals of a chimeric T7/T3 RNA polymerase with T3 promoter specificity and a nonprocessive T7 RNAP mutant. AB - Two RNA polymerases homologous to bacteriophage T7 RNA polymerase, bacteriophage Sp6 and T3 RNA polymerases, were screened for crystallization under conditions identical or similar to those reported for the growth of large single crystals of T7 RNA polymerase (Sousa, R., Rose, J. P., Chung, Y. J., Lafer, E. M., and Wang, B.-C. (1989) Proteins 5, 266; Sousa, R., Lafer, E. M., and Wang, B.-C. (1990) J. Crystal Growth, in press; Sousa, R., and Lafer, E. M. (1990) Methods 1, in press). A number of mutant T7 RNAPs were also screened under these conditions as were three chimeric RNA polymerases consisting of T7 RNAP N-terminal and T3 RNAP C-terminal sequences. One chimeric polymerase and two mutant polymerases crystallized readily under T7 RNAP crystallization conditions. The chimeric polymerase crystallized in a space group different from T7 RNA polymerase: orthorombic with unit cell parameters a = 75 A, b = 98 A, c = 159 A; space group P2(1)2(1)2(1) and 4 molecules/unit cell. This chimeric enzyme exhibits T3 promoter specificity and will make it possible to investigate how structural differences between the T3 and T7 RNA polymerase promoter recognition domains determine their different promoter specificities. One of the mutant polymerases successfully crystallized was an enzyme which can carry out promoter recognition and abortive transcription but cannot carry out processive transcription. Its structure may provide information on the nature of the conformational changes undergone by T7 RNAP in the abortive-processive switch. Crystals of the second mutant T7 RNA polymerase were unsuitable for x-ray analysis. PMID- 2254306 TI - Oscillatory synthesis of glucose 1,6-bisphosphate and frequency modulation of glycolytic oscillations in skeletal muscle extracts. AB - Oscillatory behavior of glycolysis in cell-free extracts of rat skeletal muscle involves bursts of phosphofructokinase activity, due to autocatalytic activation by fructose-1,6-P2. Glucose-1,6-P2 similarly might activate phosphofructokinase in an autocatalytic manner, because it is produced in a side reaction of phosphofructokinase and in a side reaction of phosphoglucomutase using fructose 1,6-P2. When muscle extracts were provided with 1 mM ATP and 10 mM glucose, glucose-1,6-P2 accumulated in a stepwise, but monotonic, manner to 0.7 microM in 1 h. The stepwise increases occurred during the phases when fructose-1,6-P2 was available, consistent with glucose-1,6-P2 synthesis in the phosphoglucomutase side reaction. Addition of 5-20 microM glucose-1,6-P2 increased the frequency of the oscillations in a dose-dependent manner and progressively shortened the time interval before the first burst of phosphofructokinase activity. Addition of 30 microM glucose-1,6-P2 blocked the oscillations. The peak values of the [ATP]/[ADP] ratio were then eliminated, and the average [ATP]/[ADP] ratio was reduced by half. In the presence of higher, near physiological concentrations of ATP and citrate (which reduce the activation of phosphofructokinase by glucose 1,6-P2), high physiological concentrations of glucose-1,6-P2 (50-100 microM) increased the frequency of the oscillations and did not block them. We conclude that autocatalytic activation of phosphofructokinase by fructose-1,6-P2, but not by glucose-1,6-P2, is the mechanism generating the oscillations in muscle extracts. Glucose-1,6-P2 may nevertheless play a role in facilitating the initiation of the oscillations and in modulating their frequency. PMID- 2254307 TI - Regulation of prolyl endopeptidase activity by the intracellular redox state. AB - The activity of prolyl endopeptidase was markedly decreased during incubation of intact murine erythroleukemia cells at 45 degrees C, but not during incubation of sonicated cells or during incubation at 42 degrees C. The thermal inactivation of prolyl endopeptidase in situ required neither the synthesis of proteins and polynucleotides nor the synergistic activation of inhibitors. Moreover, inhibition of lysosomal proteinases and calpains or depletion of ATP did not affect the thermal inactivation of prolyl endopeptidase. This specific inactivation of prolyl endopeptidase was also observed following the addition to the culture medium of menadione or diamide, compounds known to increase intracellular oxidized glutathione levels. The activity of prolyl endopeptidase in the cell lysate was also dose-dependently decreased by the addition of glutathione disulfide and the decrease of the activity was prevented by coexistence of reduced glutathione. Furthermore, the level of intracellular oxidized glutathione was increased during incubation at 45 degrees C for 15 min, but not at 42 degrees C for 30 min. These results strongly suggest that the activity of prolyl endopeptidase is regulated by changes in the intracellular redox potential. PMID- 2254308 TI - Fine localization of the major alpha-bungarotoxin binding site to residues alpha 189-195 of the Torpedo acetylcholine receptor. Residues 189, 190, and 195 are indispensable for binding. AB - alpha-Bungarotoxin blocks acetylcholine-mediated ion channel opening of peripheral acetylcholine receptors (AChR). A major binding region for alpha bungarotoxin has been recently identified within parts of the segment 170-204 of the alpha-subunit. We used the Pepscan systematic peptide synthesis system to determine the minimum Torpedo AChR segment required for alpha-bungarotoxin binding and to investigate the role of each residue within this segment. Continuously overlapping decapeptides within alpha 179-203 and several decapeptides covering other alpha-subunit sequences showed that alpha 188-197 and alpha 189-198 exhibited the best 125I-alpha-bungarotoxin binding activity (KD = 7.3 x 10(-8) and 4.3 x 10(-8) M, respectively). Several continuously overlapping nona-, octa-, hepta-, hexa-, and tetrapeptides showed that the heptapeptide alpha 189-195 was the minimum sequence with high binding activity (KD = 5.6 x 10(-8)M). d-Tubocurarine, but not carbamylcholine, blocked toxin binding. Twenty-six analogs of the alpha 188-197, most having 1 residue substituted by Ala or Gly, showed that Tyr189, Tyr190, and especially Asp195 were indispensable for 125I alpha-bungarotoxin binding. Cys192 and Cys193 could be substituted by other amino acids, proving that the disulfide bond between alpha 192-193 was not required for alpha-bungarotoxin binding. The decreased alpha-bungarotoxin binding capacity of the equivalent human muscle AChR alpha 188-197 peptide was the result of substitution of Tyr by Thr at alpha 189. PMID- 2254309 TI - The role of Leu-190 in the function and stability of adenylate kinase. AB - To elucidate the role of C-terminal region of chicken adenylate kinase (a single polypeptide consisting of 193 amino acid residues) in the catalysis and stability of the enzyme, a series of mutant proteins truncated in the C-terminal region has been prepared by successive replacements of the sense codons by a termination codon via site-directed mutagenesis. Removal of the three C-terminal residues did not affect the apparent Michaelis constants (Km values) for AMP and ATP, although the Vmax values decreased gradually in parallel with the length of the polypeptide chain. A sudden increase in Km values for substrates, in particular for ATP, was observed on removal of one additional residue (Leu-190), the Vmax value also being less than one-half of that of the mutant enzyme with 3 residues shorter than the wild-type enzyme. These results suggest the importance of the highly conservative Leu-190. Therefore, we further prepared the mutant enzymes through replacement of Leu-190 by a variety of other amino acid residues. They all had substantially lower Vmax values and decreased thermostabilities. Their apparent Km values for ATP also changed, whereas those for AMP were affected to a lesser extent. The hydrophobicity of amino acid residues at position 190 was found to positively correlate with the specificity constants (kcat/Km values) for ATP and also with the thermostability of the enzyme. The fluorescence emission of the Trp-190 mutant enzyme was quenched by the addition of ATP. It is suggested that the C-terminal residues, particularly those around Leu-190, are present in a hydrophobic region which may be involved in binding of ATP. PMID- 2254310 TI - Specificity of yeast KEX2 protease for variant human proalbumins is identical to the in vivo specificity of the hepatic proalbumin convertase. AB - Yeast KEX2 protease was examined as a potential model for a human proprotein convertase and, in all respects, mimicked the predicted properties of a proalbumin convertase. The enzyme rapidly cleaved the propeptide Arg-Gly-Val-Phe Arg-Arg from the NH2-terminal end of proalbumin but, unlike trypsin, failed to cleave physiologically unprocessed human proalbumin variants. There was little or no cleavage of proalbumin Lille (Arg-2----His) or Christchurch (Arg-1----Gln), and there was negligible cleavage of proalbumin Blenheim (Asp1----Val), despite the fact that it retains the dibasic processing signal. Proalbumin Kaikoura (Arg 2----Cys), which appears to be partially processed in vivo, was cleaved at about half the rate of normal proalbumin despite the absence of a diarginyl sequence. Restoration of a dibasic site through aminoethylation of the new cysteine increased the rate of cleavage to near that of normal proalbumin. The KEX2 catalyzed cleavage of normal proalbumin was found to be independent of pH between pH 6.0 and 8.0. Antitrypsin Pittsburgh (Met358----Arg), a predicted specific inhibitor of in vivo proalbumin cleavage, inhibited KEX2 in a reversible manner. A molar excess of thrombin over antitrypsin Pittsburgh relieved the inhibition of KEX2, suggesting that a covalent complex is not formed between KEX2 and the inhibitor. PMID- 2254311 TI - Probing the role of glutamic acid 144 in the EcoRI endonuclease using aspartic acid and glutamine replacements. AB - The x-ray structure of the EcoRI endonuclease-DNA complex (3) suggests that hydrogen bonds between amino acids, glutamic acid 144, arginine 145, and arginine 200, and major groove base moieties are the molecular determinants of specificity. We have investigated residue 144 using aspartate and glutamine substitutions introduced by site-directed mutagenesis. Substitution with glutamine results in a null phenotype (at least a 2000-fold reduction in activity). On the other hand, the aspartic acid mutant (ED144) retained in vivo activity. Substrate binding and catalytic studies were done with purified ED144 enzyme. The affinity of the ED144 enzyme for the canonical sequence 5'-GAATTC-3' is about 340-fold less than the wild-type (WT) enzyme, while its affinity for nonspecific DNA is about 50 times greater. The ED144 enzyme cleaves one strand in the EcoRI site in plasmid pBR322 with a kcat/Km similar to WT. In contrast to the WT enzyme, the ED144 enzyme dissociates after the first strand cleavage. Partitioning between cleavage and dissociation at the first and second cleavage steps for the ED144 enzyme is extremely salt-sensitive. The altered partitioning results largely from a destabilization of the enzyme-DNA complex, particularly the enzyme-nicked DNA complex, with only small changes in the respective cleavage rates. The hydrogen bonds of Glu-144 are critical, they appear to act cooperatively with other specificity contacts to stabilize the enzyme-DNA complex. PMID- 2254312 TI - pheAo mutants of Escherichia coli have a defective pheA attenuator. AB - Two classes of mutants affecting the regulation of pheA expression in Escherichia coli have been reported previously: trans-acting mutants involving the locus pheR, and cis-acting mutants involving the locus pheAo. The effects of these mutants have been found to be mediated through one regulatory mechanism. The gene pheR has been shown to encode tRNA(Phe) (Gavini, N., and Davidson, B. E. (1990) J. Biol. Chem. 265, 21527-21531). In this paper we report the cloning and nucleotide sequencing of the promoter-attenuator regions from two of the cis acting mutants pheAo351 and pheAo352. Both pheAo351 and pheAo352 contained a G:C to A:T base pair transition, at different positions in the 3:4 stem of the pheA attenuator terminator. Since these changes would destabilize the G:C stem of the attenuator terminator we propose that the enhanced expression of pheA observed in the pheAo mutants is due to increased transcription readthrough at the defective attenuator terminator. PMID- 2254313 TI - Acute and chronic ethanol treatment in vivo increases malate-aspartate shuttle capacity in perfused rat liver. AB - The effects of acute and chronic treatment with ethanol on transport of reducing equivalents into mitochondria via the malate-aspartate shuttle were studied in perfused rat liver. The shuttle capacity was estimated from the decrease in rates of glucose production from the reduced substrate sorbitol caused by an increase in the NADH/NAD+ ratio in the cytosol due to metabolism of ethanol. The greater the capacity of the malate-aspartate shuttle, the smaller the inhibition of glucose synthesis by ethanol. Glucose synthesis was decreased about 2-fold less in livers from fasted rats treated acutely 2.5 h earlier with ethanol than in untreated controls. Chronic treatment with ethanol for 3-5 weeks prevented completely the decrease in glucose synthesis from sorbitol due to ethanol oxidation. Rates of ethanol uptake were elevated significantly from 69 +/- 7 mumols/g/h in livers from control rats up to 92 +/- 7 mumols/g/h in livers from SIAM rats. Similarly, rates of ethanol uptake were stimulated by chronic ethanol treatment from 71 +/- 6 to 222 +/- 15 mumols/g/h; this increase was largely sensitive to aminooxyacetate. Taken together, these data indicate that flux of reducing equivalents over the malate-aspartate shuttle is increased by both acute and chronic treatment with ethanol and that movement of reducing equivalents from the cytosol into the mitochondria via the malate-aspartate shuttle is an important rate determinant in hepatic ethanol oxidation. PMID- 2254314 TI - Evidence that both Ca(2+)-specific sites of skeletal muscle TnC are required for full activity. AB - To investigate the role of the Ca2(+)-specific (I and II) sites of fast skeletal muscle troponin C (TnC) in the regulation of contraction, we have produced two TnC mutants which have lost the ability to bind Ca2+ at either site I (VG1) or at site II (VG2). Both mutants were able to partially restore force to TnC-depleted skinned muscle fibers (approximately 25% for VG1 and approximately 50% for VG2). In contrast, bovine cardiac TnC (BCTnC), which like VG1 binds Ca2+ only at site II, could fully reactivate the contraction of TnC-depleted fibers. Higher concentrations of both mutants were required to restore force to the TnC-depleted fibers than with wild type TnC (WTnC) or BCTnC. VG1 and VG2 substituted fibers could not bind additional WTnC, indicating that all of the TnC-binding sites were saturated with the mutant TnC's. The Ca2+ concentration required for force activation was much higher for VG1 and VG2 substituted fibers than for WTnC or BCTnC substituted fibers. Also, the steepness of force activation was much less in VG1 and VG2 versus WTnC and BCTnC substituted fibers. These results suggest cooperative interactions between sites I and II in WTnC. In contrast, BCTnC has essentially the same apparent Ca2+ affinity and steepness of force activation as does WTnC. Thus, cardiac TnC must have structural differences from WTnC which compensate for the lack of site I, while in WTnC, both Ca2(+)-specific sites are probably crucial for full functional activity. PMID- 2254315 TI - Structure of chicken 16-kDa beta-galactoside-binding lectin. Complete amino acid sequence, cloning of cDNA, and production of recombinant lectin. AB - The complete primary structure of chicken 16-kDa beta-galactoside-binding lectin (C-16) was determined. It was composed of 134 amino acid residues and has an acetylated NH2 terminus. A cDNA was also cloned, but no signal sequence was found in the initiator region. The initiator methionine remained as the NH2 terminus of the mature lectin. Although C-16 is distinct from chicken 14-kDa beta-galactoside binding lectin (C-14), it proved to be a member of the vertebrate 14-kDa-type lectin family. Comparison of the primary structures between the vertebrate 14-kDa type lectins suggests that C-14 and C-16 were produced by gene duplication of an ancestral lectin gene at a time close to the divergence of birds and mammals. Northern and Southern blot analysis indicated that these isolectins are encoded by individual genes which are differently regulated during the development of the embryo. A recombinant C-16 lectin was produced in Escherichia coli. The product was indistinguishable from the authentic C-16 lectin except that the NH2 terminus of the former was found to begin with free methionine. PMID- 2254316 TI - Identification and characterization of a phospholipid-binding site of bovine factor Va. AB - Coagulation factor Va is a cofactor which combines with the serine protease factor Xa on a phospholipid surface to form the prothrombinase complex. The phospholipid-binding domain of bovine factor Va has been reported to be located on the light chain of the molecule and more precisely on a fragment of Mr = 30,000 which is obtained after digestion of factor Va light chain by factor Xa. This proteolytic fragment is located in the NH2-terminal part of factor Va light chain (residues 1564-1765). In order to further characterize the lipid-binding domain of bovine factor Va, isolated bovine light chain was preincubated with synthetic phospholipid vesicles (75% phosphatidylcholine, 25% phosphatidylserine) and digested with trypsin, chymotrypsin, and elastase. Two peptide regions protected from proteolytic cleavage were identified and characterized from each proteolytic digestion. A comparison of the NH2-terminal sequence and amino acid composition of the two tryptic peptides with the deduced sequence of human factor V indicates a match with residues 1657-1791 of the light chain of human factor V for one peptide and residues 1546-1656 for the other peptide. When chymotrypsin or elastase were used for digestion, the NH2-terminal sequence of one peptide showed a match with residues 1667-1797 of the light chain, while the other peptide presented an NH2-terminal sequence identical with the previously described for the bovine factor Va light chain. When these peptides were assayed for direct binding to phospholipid vesicles, only the tryptic and the chymotryptic peptides covering the middle region of the A3 domain of the bovine factor Va light chain demonstrated an ability to interact with phospholipid vesicles. Thus, knowing that the factor Xa cleavage site on the factor Va light chain is located between residues 1765 and 1766 of the light chain this lipid binding region of the bovine factor Va is further localized to amino acid residues 1667-1765. PMID- 2254317 TI - The mechanism of cysteine conjugate cytotoxicity in renal epithelial cells. Covalent binding leads to thiol depletion and lipid peroxidation. AB - Nephrotoxic cysteine conjugates kill cells after they are metabolized by the enzyme cysteine conjugate beta-lyase to reactive fragments which bind to cellular macromolecules. We have investigated the cellular events which occur after the binding and lead ultimately to cell death in renal epithelial cells. Using S-(1,2 dichlorovinyl)-L-cysteine (DCVC) as a model conjugate, we found that the phenolic antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD), butylated hydroxyanisole, butylated hydroxytoluene, propyl galate, and butylated hydroxyquinone, and the iron chelator deferoxamine inhibited the cytotoxicity significantly. Among the five antioxidants, DPPD was most potent. DPPD blocked DCVC toxicity over an extended time period, and the rescued cells remained functional as measured by protein synthetic activity. DPPD was able to block the toxicity of two other toxic cysteine conjugates S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine and S (1,1,2,2-tetrafluoroethyl)-L-cysteine. In addition to LLC-PK1 cells, DPPD also protected freshly isolated rat kidney epithelial cells in suspension and in primary culture. In suspension cells, DPPD was effective at low doses of DCVC (25 50 microM) but not at high concentrations (250-500 microM). DPPD inhibition was not due to an inactivation of beta-lyase or a decrease in the binding of [35S]DCVC metabolites to cellular macromolecules and occurred at a step after the activation of the toxins. During DCVC treatment, lipid peroxidation products were detectable prior to cell death. DPPD blocked lipid peroxidation over the whole time course. Depletion of nonprotein thiols also occurred prior to cell death. DPPD did not prevent the loss of nonprotein thiols. However, the sulfhydryl reducing agent DTT blocked lipid peroxidation and toxicity at a step after the activation of DCVC. Therefore, it appears that cysteine conjugates kill renal epithelial cells by a combination of covalent binding, depletion of nonprotein thiols, and lipid peroxidation. PMID- 2254318 TI - Contribution of conformational stability and reversibility of unfolding to the increased thermostability of human and bovine superoxide dismutase mutated at free cysteines. AB - The conformational stability and reversibility of unfolding of the human dimeric enzyme Cu Zn superoxide dismutase (HSOD) and the three mutant enzymes constructed by replacement of Cys6 by Ala and Cys111 by Ser, singly and in combination, were determined by differential scanning calorimetry. The differential scanning calorimetry profile of wild-type HSOD consists of two components, which probably represent the unfolding of the oxidized and reduced forms of the enzyme, with denaturation temperatures (Tm) of 74.9 and 83.6 degrees C, approximately 7 degrees lower than those for bovine superoxide dismutase (BSOD). The conformational stabilities of the two components of the mutant HSOD's differ only slightly from those of the wild type (delta delta Gs of -0.2 to +0.8 kcal/mol of dimer), while replacement of the BSOD Cys6 by Ala is somewhat destabilizing (delta delta G of -0.7 to -1.3 kcal/mol of dimer). These small alterations in conformational stability do not correlate with the large increases in resistance to thermal inactivation following substitution of free Cys in both HSOD and BSOD (McRee, D.E., Redford, S.M., Getzoff, E.D., Lepock, J.R., Hallewell, R.A., and Tainer, J.A. (1990) J. Biol. Chem. 265, 14234-14241 and Hallewell, R.A., Imlay, K.C., Laria, I., Gallegos, C., Fong, N., Irvine, B., Getzoff, E.D., Tainer, J.A., Cubelli, D.E., Bielski, B.H.J., Olson, P., Mallenbach, G.T., and Cousens, L.S. (1991) Proteins Struct. Funct. Genet., submitted for publication). The reversibility of unfolding was determined by scanning part way through the profile, cooling, rescanning, and calculating the amount of protein irreversibly unfolded by the first scan. The order of reversibility at a constant level of unfolding is the same as the order of resistance to inactivation for both the HSOD and BSOD wild-type and mutant enzymes. Thus, the greater resistance to thermal inactivation of the superoxide dismutase enzymes with free Cys replaced by Ala or Ser is dominated by a greater resistance to irreversible unfolding and relatively unaffected by changes in conformational stability. PMID- 2254319 TI - A novel sialidase which releases 2,7-anhydro-alpha-N-acetylneuraminic acid from sialoglycoconjugates. AB - The leech (Macrobdella decora) was found to contain two sialic acid-cleaving enzymes: an ordinary sialidase and a novel sialic acid-cleaving enzyme. This novel enzyme released 2,7-anhydro-alpha-N-acetylneuraminic acid (Neu2,7 anhydro5Ac) instead of alpha-N-acetylneuraminic acid (Neu5Ac) from 4 methylumbelliferyl-Neu5Ac, glycoproteins, and gangliosides. We have partially purified this novel sialidase from M. decora. We have also isolated Neu2,7 anhydro5Ac released from 4-methylumelliferyl-Neu5Ac and whale nasal keratan sulfate in pure form. The novel sialidase produced Neu2,7-anhydro5Ac only from sialoglycoconjugates, but not from free Neu5Ac. The structure of Neu2,7 anhydro5Ac produced by the novel sialidase was established by chemical analysis, mass spectrometry, and NMR spectroscopy. NMR analysis showed that instead of the original 2C5 conformation, the pyranose ring of Neu2,7-anhydro5Ac was in the 5C2 conformation, which makes the formation of the 2,7-anhydro bridge possible. PMID- 2254320 TI - TE671 cells express an abundance of a partially mature acetylcholine receptor alpha subunit which has characteristics of an assembly intermediate. AB - A partially mature form of the nicotinic acetylcholine receptor alpha subunit was found to be expressed in the human cell line TE671. We found that 40-50% of the alpha-bungarotoxin-binding sites in detergent extracts of these cells corresponds to this unassembled alpha subunit. These unassembled alpha subunits are not found in the surface membrane. The unassembled alpha subunits in extracts from TE671 cells appear, like mature receptors, to have a disulfide bond between Cys-192 and Cys-193 near the acetylcholine-binding site. The unassembled alpha subunit binds alpha-bungarotoxin with high affinity, but its dissociation constant is still 5 fold higher than the native assembled acetylcholine receptor. The cholinergic ligands d-tubocurarine and carbamylcholine have negligible affinity for the immature alpha subunit. Similarly, Xenopus oocytes injected with RNA transcripts for the TE671 alpha subunit express an alpha-bungarotoxin-binding component which is insensitive to carbamylcholine and has a sedimentation coefficient on sucrose gradients of 5.0 S. Oocytes injected with RNA for the Torpedo alpha subunit did not have alpha-bungarotoxin binding activity under similar conditions, suggesting a possible differential efficiency in the maturation of this alpha subunit. We examined the binding of monoclonal antibodies specific to the main immunogenic region and found that this epitope on the unassembled alpha subunit was formed, but was not in a fully mature conformation because although these antibodies bound, they bound with lower affinity than to native acetylcholine receptors. Antibodies in myasthenia gravis patient sera also bound to the unassembled alpha subunits, but with an average 14-fold lower titer. PMID- 2254321 TI - Kinetic characterization of a prestart cell division control step in yeast. Implications for the mechanism of alpha-factor-induced division arrest. AB - In Saccharomyces cerevisiae yeast, a cycloheximide-sensitive "prestart" step (Ki = 0.12 +/- 0.05 microM) is passaged greater than or equal to 4 to less than or equal to 13 minutes prior to the alpha-factor-sensitive "Start" step in the cell cycle of normal proliferating cells and in the first and second bud emergence cycles of abnormally large cells that had been arrested for cell division with alpha-factor and allowed to recover. This identifies the chronologically last protein synthetic step of the cell cycle that occurs prior to the completion of Start. This step is named the last synthetic prestart or LSP step. Cells require the completion of the LSP step before they can perform Start during recovery from arrest by alpha-factor. Yet alpha-factor is known to prevent cell division by acting at Start. The combined data suggest that alpha-factor prevents the Start step of cell division by inactivating a protein that is 1) required for the performance of Start, and 2) synthesized shortly prior to Start in the last synthetic prestart step. PMID- 2254322 TI - Isolation and molecular cloning of transferrin from the tobacco hornworm, Manduca sexta. Sequence similarity to the vertebrate transferrins. AB - An iron-binding glycoprotein of Mr = 77,000 has been isolated from hemolymph of the adult sphinx moth Manduca sexta. Since this protein binds ferric ion both in vivo and in vitro and has a secondary structure similar to that of human serum transferrin and human lactoferrin as judged by CD spectra, we decided to clone its cDNA in order to determine its relationship to the vertebrate transferrins. Antiserum generated against this protein was used to screen a larval fat body cDNA library. A 2.0 kilobase clone was isolated that selects an mRNA which, when translated in vitro, produces an immunoprecipitable 77-kDa protein. When the library was rescreened using the 2.0-kilobase clone as a probe, three full-length clones were isolated, and the complete nucleotide sequence of one 2,183-base pair insert was determined. The deduced protein sequence contains an 18-amino acid signal sequence and a mature protein sequence of 663 amino acids with a calculated Mr of 73,436. The sequence was used to search the National Biomedical Research Foundation (NBRF) protein database, revealing significant similarity to the vertebrate transferrins, a family of 80-kDa glycoproteins which transport and sequester iron in the blood and other body fluids. A multiple sequence alignament shows the greatest areas of similarity to be around the two iron binding sites, although the insect protein seems to contain only one such functional site. Moreover, 23 of the 24 cysteine residues in the insect protein occupy identical positions as compared with the other transferrins, indicating a similar overall tertiary structure. Comparison of the two halves of the insect sequence indicates that the protein may have arisen as a result of gene duplication. The similarity of the M. sexta sequence to the vertebrate transferrins may provide important clues to transferrin evolution. PMID- 2254323 TI - Bifunctional thrombin inhibitors based on the sequence of hirudin45-65. AB - The interaction of alpha-thrombin with the hirudin (HV1) fragment N alpha-acetyl desulfo hirudin45-65 (P51) was investigated. Kinetic analysis revealed that P51 inhibits the proteolysis of a tripeptidyl substrate with Ki = 0.72 +/- 0.13 and 0.11 +/- 0.03 microM for bovine and human alpha-thrombins, respectively. The inhibition was partially competitive, affecting substrate binding to the enzyme inhibitor complex by a factor alpha = 2 (bovine) and alpha = 4 (human) characteristic of hyperbolic inhibitors. P51 also inhibited thrombin-induced fibrin clot formation with IC50 values of 0.94 +/- 0.20 and 0.058 +/- 0.006 microM for bovine and human alpha-thrombins, respectively. The enhanced antithrombin activity for human thrombin could be attributed to species variations in the putative auxiliary "anion" exosite since N alpha-acetyl desulfo hirudin55-65 displayed the same rank order of potency shift in a clotting assay without inhibiting the amidolytic activity of either enzyme. From these observations, a potent thrombin inhibitor was designed having modified residues corresponding to the P1 and P3 recognition sites. N alpha-Acetyl[D-Phe45, Arg47] hirudin45-65 (P53) emerged as a pure competitive inhibitor with a Ki = 2.8 +/- 0.9 nM and IC50 = 4.0 +/- 0.8 nM (human alpha-thrombin) and is designated as a "bifunctional" inhibitor. Its enhanced potency could be explained by a cooperative intramolecular interaction between the COOH-terminal domain of the inhibitor and the auxiliary exosite of thrombin on the one hand, and the modified NH2-terminal residues with the catalytic site on the other. PMID- 2254324 TI - Nucleotide sequence of gltS, the Na+/glutamate symport carrier gene of Escherichia coli B. AB - The nucleotide sequence of the gltS gene coding for an Na+/glutamate symport carrier of Escherichia coli B has been determined, and the amino acid sequence of the carrier protein was deduced. The predicted glutamate carrier consists of 401 amino acids with a molecular weight of 42,455. A Shine-Dalgarno sequence and putative promoter sequences were found in the 5'-flanking region of the putative gltS gene. The predicted protein is very hydrophobic (73% nonpolar amino acids), and judging from its hydropathy profile, the protein is composed of 12 hydrophobic membrane-spanning segments with a mean length of 21.6 residues/segment. A typical rho-independent transcription termination signal was found downstream of the gltS gene. We found a conserved alignment of 5 amino acid residues (Gly42--Ala82-X-X-X-X-Leu87-X-X-X-Gly91-Arg92 ), which commonly exists in four Na+ symport carrier proteins, the glutamate carrier, and the proline carrier of E. coli, and the Na+/glucose co-transporters of rabbit and human intestines. We propose that this consensus sequence (or motif) may play an important role in cation recognition or binding in the Na+/solute symport reaction. PMID- 2254325 TI - Metabolism of phosphatidylglycerol and bis(monoacylglycero)-phosphate in macrophage subcellular fractions. AB - Bis(monoacylglycero)phosphate (BMP) is synthesized from exogenous phosphatidylglycerol (PG) by macrophages (Cochran, F. R., Roddick, V. L., Connor, J. R., Thornburg, J. T., and Waite, M. (1987) J. Immunol. 138, 1877-1883). Previous work from our laboratory showed that arachidonic acid in BMP was released by the macrophages upon challenge of the cells with PMA (Cochran, F. R., Connor, J. R., Roddick, V. L., and Waite, M. (1985) Biochem. Biophys. Res. Commun. 130, 800-806). Here we extend those studies using a model cultured cell line of macrophages, RAW 264.7. When PG labeled with 32P- and [3H]glycerol in both moieties was added to the culture medium, 32P/[3H]BMP was synthesized in a time-dependent manner. Fractionation of cell homogenates on a discontinuous sucrose gradient in which the light membranes were floated from dense sucrose showed an enrichment of [3H]BMP in light membrane fractions. The precursor [3H]PG was also found in the light fractions but, relative to the [3H]BMP, was more abundant in the denser membrane fractions. The appearance of [3H]PG and [3H]BMP in the light membrane fraction was time-dependent which suggested that the initial uptake and metabolism of [3H]PG was into the denser membranes. Incubation of the light membranes under conditions that are optimal for the lysosomal phospholipase A1 led to significant metabolism of [3H]PG. Both degradation of [3H]PG to water-soluble compounds and its conversion to acylphosphatidylglycerol occurred while no lyso-PG was detected. On the other hand, little BMP was found to be degraded. From these studies we postulate that in lysosomes acylphosphatidylglycerol is a precursor of BMP and that the previously reported turnover of arachidonic acid by BMP may occur via transacylation rather than hydrolysis. PMID- 2254326 TI - Characterization of affinity-purified juvenile hormone esterase from the plasma of the tobacco hornworm, Manduca sexta. AB - Juvenile hormone (JH) esterase found primarily in the hemolymph and tissues of insects is a low abundance protein involved in the ester hydrolysis of insect juvenile hormones, JHs. The enzyme was purified from the larval plasma of wild type Manduca sexta using an affinity column prepared by binding the ligand, 3 [(4'-mercapto)butylthio]-1,1,1-trifluoropropan-2-one (MBTFP), to epoxy-activated Sepharose. The purification was greater than 700-fold with a 72% recovery, and the purified enzyme appeared as a single protein on sodium dodecyl sulfate polyacrylamide gel electrophoresis, immunoelectrophoresis, reverse phase high performance liquid chromatography, and amino acid sequence analysis. The molecular weight was 66,000. The plasma JH esterase in wild-type, black, and white strains of M. sexta was similar when analyzed by immunotitration, wide range (pH 3.5-9.0) isoelectric focusing, and inhibition with MBTFP and 3 octylthio-1,1,1-trifluoropropan-2-one (OTFP). Inhibition studies revealed a sensitive and insensitive form (I50 = 10(-9) and 10(-6) M, respectively) in these three biotypes. Narrow range isoelectric focusing (pH 4.0-7.0) indicated the presence of two major isoelectric forms with pI values of 6.0 and 5.5, but their inhibition kinetics with OTFP and O,O-diisopropyl phosphorofluoridate were identical. PMID- 2254327 TI - Purification and characterization of the nuclear factor BA1. A transcriptional activator of the human apoB gene. AB - The promoter region of human apoB -79 to -63 is recognized by a sequence-specific DNA binding protein, designated NF-BA1, which is essential for the transcriptional activation of the apoB gene in hepatic and intestinal cells. This protein has been purified to apparent homogeneity from rat liver nuclear extracts. The purification steps involve Q-Sepharose, Bio-Rex 70, S-Sepharose, and DNA-specific affinity chromatography. The purified protein was identified as a polypeptide of 60 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity cross-linking. In vitro transcription complementation experiments using normal and mutated -268 to +8 apoB promoter sequences as templates indicated that the purified protein retained the ability to stimulate apoB transcription when added to hepatic nuclear extracts. The stimulation of transcription is associated with the binding of the factor to its recognition sequence. A synthetic promoter consisting of five contiguous -79 to 63 elements in front of the core apoB promoter region -38 to +8 is strongly activated by NF-BA1 protein in hepatic extracts in vitro. Footprinting analysis showed that purified NF-BA1 binds to the regulatory regions of apoCIII (-87 to 63), apoAII (-740 to -719), and apoAI (-212 to -191) genes and may be involved in the regulation of their expression. PMID- 2254328 TI - Compartmentation and turnover of the low density lipoprotein receptor in skin fibroblasts. AB - The low density lipoprotein receptor (LDLR) was immunoprecipitated from [35S]methionine-labeled skin fibroblasts derivatized at 4 or 18 degrees C with an impermeant biotinylating reagent. Separation of derivatized and underivatized receptor from immunoprecipitates by selective binding to streptavidin-agarose allowed assessment of receptor protein cellular compartmentation and rates of intercompartmental transfer. At both 4 and 18 degrees C the amount of LDLR that is derivatized in cells labeled to near steady state saturates after 1-2 h of reaction at, respectively, 47 and 70% of total immunoprecipitable receptor protein. On the basis of temperature titration experiments, protein exposed only to the cell surface reacts at 4 degrees C; raising the temperature of biotinylation to 18 degrees C provides access to an additional pool of receptor protein. Remaining LDLR is derivatized at 37 degrees C. LDLR unreactive at 18 degrees C largely resides in membrane compartment(s) devoid of plasma membrane on the basis of its fractionation on Percoll gradients. While total cellular LDLR and 4 degrees C-derivatized LDLR labeled to steady state turn over in a first order manner (t1/2 = 12-13 h), the specific activity of pulse-labeled, 4 degrees C-accessible protein peaks after 1-2 h of chase and reaches a reduced level by 3 h of chase. These latter results show that the newly synthesized LDLR is transiently enriched at the cell surface prior to achieving equilibrium distribution between the cell surface and intracellular pools. PMID- 2254329 TI - Cadmium uptake by cells of renal origin. AB - We compared the ability of rat glomerular mesangial cells and LLC-PK1 cells to take up Cd2+ from solution. The former are smooth muscle-like cells of mesenchymal origin, the latter an established line of proximal tubular epithelium. Both cells, as well as primary glomerular epithelia, accumulated Cd2+ against a concentration gradient in a time-dependent manner. Uptake by mesangial cells obeyed a Michaelis model with an apparent Km of 19 microM and could be described by an initial rapid step of surface binding followed by rate-limiting internalization. In contrast, uptake by LLC-PK1 cells was non-saturable under accessible concentrations of Cd2+ and internalization was not a necessary consequence of association with the cell surface. In several other cell types, Cd2+ uptake has been shown to be inhibited by blockage of cell-surface sulfhydryl groups. In contrast, uptake by neither mesangial nor LLC-PK1 cells was depressed by N-ethylmaleimide, which actually enhanced the surface binding and to a lesser extent the uptake by the LLC-PK1 cell line. Neither depended on metabolic energy for uptake or utilized Ca2+ channels. The internalization process was temperature dependent and was obliterated at 2 degrees C. In mesangial cells, this allowed direct observation of the internalization event from a presaturated surface pool. The rate of this process was consistent with the Vmax calculated from the Michaelis model. Surface binding and uptake were decreased by binding of Cd2+ to serum proteins and albumin and were much less dependent on the presence of low molecular weight components of serum. Therefore, these cells may be especially sensitive to Cd2+ at concentrations encountered in vivo because of the low protein content of the plasma ultrafiltrate. Surface binding of Cd2+ to mesangial cells was suppressed by competing divalent ions following the order of the Irving Williams series (Mn less than Co less than Ni less than Cu greater than Zn), although Zn2+ showed the greatest effect on internalization. In LLC-PK1 cells, Zn2+ and Cu2+ were both effective in decreasing Cd2+ uptake. We conclude that Cd2+ uptake by the tubular epithelial cells is rapid and independent of specific cell surface interactions, whereas uptake by rat mesangial cells follows binding to a specific surface ligand saturating at about 1.5 x 10(7) copies/cell. In both types of cells the uptake appears quite specific for Cd2+ and shows some cross reactivity with other metal cations explicable by competitive ligand binding. PMID- 2254330 TI - Protein-based asymmetry and protein-protein interactions in FLP recombinase mediated site-specific recombination. AB - When the FLP recombination target (FRT) is cut in half so that only one FLP protein-binding site is present, FLP protein forms a complex in which two such sites are linked head to head. Although held together exclusively by noncovalent interactions, this complex survives electrophoresis in an agarose gel and exhibits a half-life that can be measured in hours. Characterization of this complex indicates that a very stable, asymmetric dimeric complex of FLP protein monomers bound to the FRT is a likely early intermediate in FLP-mediated site specific recombination. The apparent asymmetry is a property of the protein components of the complex. Even though the DNA components form a perfect palindrome, only one of the two possible DNA cleavage steps takes place in the course of complex formation. Formation of this complex does not occur with half FRT site DNA substrates that preclude head to head monomer contact or when a FLP mutant protein is used that binds the FRT site but cannot cleave it. Trimeric and tetrameric complexes are also observed, the latter at very low frequency. These results are discussed in terms of an expanded model for early events in FLP mediated site-specific recombination. PMID- 2254331 TI - Sequences near the origin of replication of the DHFR locus of Chinese hamster ovary cells adopt left-handed Z-DNA and triplex structures. AB - The earliest replicating portion of the Chinese hamster dihydrofolate reductase domain contains a cluster of simple repeated sequences 180 base pairs long composed of 5'-(GC)5(AC)18(AG)21(G)9(CAGA)4GAGGGAGAGAGGCAGAGAGGG(AG)27-3 '. Previous nuclease sensitivity and intermolecular hybridization studies suggested that the two long (AG) repeats in this tract formed intramolecular DNA triplexes in negatively supercoiled plasmids at pH 5.2 (Caddle, M. S., Lussier, R. L., and Heintz, N. H. (1990) J. Mol. Biol. 211, 19-33). To further characterize the structural organization, supercoiled plasmids containing this region were analyzed in vitro with OsO4 and diethyl pyrocarbonate probes as well as with two dimensional gel electrophoresis under different conditions. In pMCG, which contains the sequence in a 1.6-kilobase pair insert, the preferred conformation at neutral pH and at the native superhelical density is a Z-DNA structure for the (GC)5(AC)18 tract. Under mildly acidic conditions and at the native superhelical density, both (AG) tracts form intramolecular triplexes to the exclusion of the Z DNA structure. Chemical probing of topoisomers of pMCG indicates that the (AG)27 tract forms a triplex more readily than the (AG)21 motif. Also, analysis of the reactivity obtained on a larger plasmid, pMCD, which contains the cluster of repeated sequences in a 4.75-kilobase pair insert, shows that at the native superhelical density the formation of intramolecular triplexes is limited to the (AG)27 tract. Finally, experiments conducted on different populations of topoisomers of pMCG show the existence, at pH 5.0 and highly negative superhelical density (greater than or equal to 0.080), of both the left-handed and the two triple-stranded structures in the same DNA. Therefore, one triplex is located immediately adjacent to the Z helix. Companion studies revealed that this region of the DHFR replicon modulates fork translocation during the replication of recombinant plasmids in mammalian cells. PMID- 2254332 TI - Identification of the MAP2- and P75-binding domain in the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase. Cloning and expression of the cDNA for bovine brain RII beta. AB - cDNA clones coding for the regulatory subunit (RII beta) of type II cAMP dependent protein kinase were isolated from a bovine brain cDNA expression library in lambda gt11. The cDNA codes for a protein of 418 amino acids which is 98% homologous to the rat and human RII beta proteins. A series of expression vectors coding for truncated RII beta proteins were constructed in pATH plasmids and fusion proteins were expressed in Escherichia coli. Polyclonal and monoclonal antibodies made against purified bovine brain RII were immunoreactive with the fusion proteins on Western blots. The expressed RII beta-fusion proteins were used in overlay assays to identify the region in RII beta which binds to microtubule-associated protein 2 (MAP2) and to the 75,000-dalton calmodulin binding protein (P75) (Sarkar, D., Erlichman, J., and Rubin, C.S. (1984) J. Biol. Chem. 259, 9844-9846) in bovine brain. Fusion protein containing amino acids 1-50 of the RII beta NH2 terminus (RII beta(1-50)] bound to both MAP2 and P75 immobilized on nitrocellulose filters. A pATH11-directed fusion protein containing the 31 amino acid RII-binding site of the human MAP2 protein (MAP2(31)) (Rubino, H.M., Dammerman, M., Shafit-Zagardo, B., and Erlichman, J. (1989) Neuron 3, 631-638) also bound RII beta-fusion proteins containing RII beta amino acids 1-50. Three fusion proteins, RII beta(1-25), RII beta(25-96), and RII beta(1-265,25-96 deleted) did not bind to MAP2(31) nor P75. The results showed that the binding domain for MAP2 and P75 was located within the NH2-terminal 50 amino acids of RII beta. Preincubation of bovine heart protein kinase II alpha and RII beta(1-50) with MAP2(31) prevented their binding to both P75 and MAP2(31) that were immobilized on nitrocellulose, suggesting that the binding sites for MAP2 and P75 are located near each other or that the same site on RII was binding to both proteins. PMID- 2254333 TI - Deaminated neuraminic acid-rich glycoprotein of rainbow trout egg vitelline envelope. Occurrence of a novel alpha-2,8-linked oligo(deaminated neuraminic acid) structure in O-linked glycan chains. AB - Deaminated neuraminic acid-rich glycoprotein (KDN-gp), first found and isolated from the vitelline envelope of rainbow trout eggs (Inoue, S., Kanamori, A., Kitajima, K., and Inoue, Y. (1988) Biochem. Biophys. Res. Commun. 153, 172-176), has been found to contain a number of O-linked glycan. Oligosaccharides were released by alkaline borohydride treatment of KDN-gp. Following fractionation by DEAE-Sephadex A-25 and thin-layer chromatography, a series of acidic oligosaccharides were obtained and analyzed for their chemical structures. The structure is based on composition analysis, methylation analysis, alkali catalyzed "peeling" reactions, periodate oxidation, 400-MHz one- and two dimensional 1H NMR spectroscopy, and molecular secondary ion mass spectrometry. The O-linked oligosaccharides isolated from KDN-gp have been shown to contain a common core trisaccharide Gal beta 1-3GalNAc alpha 1-3GalNAc in which the terminal Gal residue is blocked by a single residue of deaminated neuraminic acid (KDN) and the proximal GalNAc residue is substituted by alpha-2,8-linked oligo(KDN) chains. Structures of KDN-oligosaccharide chains in the glycoprotein are novel and expressed by the following general formula, where n = 0-5, for which data are available. [formula: see text] PMID- 2254334 TI - Envelope membranes from mature spinach chloroplasts contain a NADPH:protochlorophyllide reductase on the cytosolic side of the outer membrane. AB - Using fluorescence spectroscopy, we have demonstrated that isolated envelope membranes from mature spinach chloroplasts catalyze the phototransformation of endogenous protochlorophyllide into chlorophyllide in presence of NADPH, but not in presence of NADH. Protochlorophyllide reductase was characterized further using monospecific antibodies (anti-protochlorophyllide reductase) raised against the purified enzyme from oat. In mature spinach chloroplasts, protochlorophyllide reductase is present only in envelope membranes. We have demonstrated that the envelope protochlorophyllide reductase, a 37,000-dalton polypeptide, is only a minor envelope component and is present on the outer surface of the outer envelope membrane. This conclusion is supported by several lines of evidence: (a) the envelope polypeptide that was immunodecorated with anti-protochlorophyllide reductase can be distinguished from the major 37,000-dalton envelope polypeptide E37 (which was identified by monospecific antibodies) only after two-dimensional polyacrylamide gel electrophoresis; (b) the envelope protochlorophyllide reductase was hydrolyzed when isolated intact chloroplasts were incubated in presence of thermolysin; and (c) isolated intact chloroplasts strongly agglutinate when incubated in presence of antibodies raised against protochlorophyllide reductase. These results demonstrate that major differences exist between chloroplasts and etioplasts with respect to protochlorophyllide reductase levels and localization. The presence on the chloroplast envelope membrane of both the substrate (protochlorophyllide) and the enzyme (protochlorophyllide reductase) necessary for chlorophyllide synthesis could have major implications for the understanding of chlorophyll biosynthesis in mature chloroplasts. PMID- 2254335 TI - Differential regulation of two glucose transporters by chronic growth hormone treatment of cultured 3T3-F442A adipose cells. AB - New methods for the analysis of glucose transporters were used to analyze the molecular mechanisms involved in the insulin-antagonistic effects of growth hormone (GH), which is known as a diabetogenic hormone. The ability of GH to alter the number and mRNA levels of two different glucose transporters in cultured 3T3-F442A adipocytes was investigated using specific antibodies and cDNA probes. At concentrations of GH as low as 0.5 and 5 ng/ml and at incubation times as short as 4 h, GH decreased rates of 2-deoxyglucose uptake in 3T3-F442A adipocytes. 3-O-Methyl-D-glucose uptake was inhibited to an extent similar to that of 2-deoxyglucose uptake (60-80%) after a 24-h incubation with GH (500 ng/ml), indicating that GH inhibits glucose metabolism specifically at the step of glucose transport. To determine whether reduced rates of glucose transport might result from reduced numbers of glucose transporters, whole cell lysates were prepared from GH-treated cells and subjected to immunoblotting using antibodies that identify Glut 1 (HepG2/rat brain) and Glut 4 (muscle/adipose) transporters. GH caused a time- and dose-dependent decrease in the number of Glut 1 transporters in the cell. Northern and slot-blot analyses showed a GH-induced dose-dependent decrease in levels of Glut 1 mRNA. In contrast, levels of Glut 4 transporter and mRNA were unchanged by GH. These data suggest that GH regulates Glut 1 and Glut 4 transporters differentially and that it exerts its inhibitory effect on glucose uptake at least in part by decreasing the synthesis of Glut 1 transporters. These studies provide the first evidence that GH regulates a key gene in metabolic regulation and can interfere with gene expression. PMID- 2254336 TI - The cDNA sequences encoding two components of the polymeric fraction of the intracellular hemoglobin of Glycera dibranchiata. AB - The intracellular hemoglobin of the polychaete Glycera dibranchiata consists of several components, some of which self-associate into a "polymeric" fraction. The cDNA library constructed from the poly(A+) mRNA of Glycera erythrocytes (Simons, P. C., and Satterlee, J. D. (1989) Biochemistry 28, 8525-8530) was screened with two oligodeoxynucleotide probes corresponding to the amino acid sequences MEEKVP and AMNSKV. Each of the two probes identified a full-length positive insert; these were sequenced using the dideoxynucleotide chain termination method. One clone was 630 bases long and contained 36 bases of 5'-untranslated RNA, a reading frame of 441 bases coding for the 147 amino acids of globin P2 including the residues MEEKVP, and a 3'-untranslated region of 153 bases. The other clone was 540 bases long and contained 24 bases of 5'-untranslated RNA, an open reading frame of 441 bases coding for globin P3 including the residues AMNSKV, and a 3' untranslated region of 75 bases. The inferred amino acid sequences of the two globins were in agreement with the partial amino acid sequences obtained by chemical methods. The P2 and P3 globin sequences, together with the previously determined P1 sequence of a complete insert and partial sequences P4, P5, and P6 obtained from partial inserts (Zafar, R. S., Chow, L. H., Stern, M. S., Vinogradov, S. N., and Walz, D. A. (1990) Biochim. Biophys. Acta, in press) suggest that there are at least six components in the polymeric fraction of Glycera hemoglobin, which is in agreement with the results of polyacrylamide gel electrophoresis in Tris/glycine buffer, pH 8.3, 6 M urea. Nothern and dot blot analyses of Glycera erythrocyte poly(A+) mRNA using the foregoing two cDNA probes clearly demonstrated the presence of mature messages encoding both types of globins. Comparison of the polymeric sequences P1, P2, and P3 with the "monomeric" globins M-II and M-IV using the alignment and templates of Bashford et al. (Bashford, D., Chothia, C., and Lesk, A. M. (1987) J. Mol. Biol. 196, 199 216) showed that all five globins have identical residues at 39 positions. At 44 positions, the three polymeric globins share identical residues that differ from the identical residues at the corresponding locations in the monomeric sequences M-II and M-IV including position E7, where the latter have leucine instead of the distal histidine. At 15 positions, there occurs an alteration from polar to nonpolar or from a small nonpolar to a larger nonpolar residue in going from the monomeric to the polymeric globins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254337 TI - Dephosphorylation-induced interactions of neurofilaments with microtubules. AB - Effects of dephosphorylation on interactions of neurofilaments (NFs) with microtubules (MTs) were studied by the cosedimentation method. Centrifugation conditions were chosen so that MTs pelleted but NFs did not. While NFs isolated from bovine spinal cords did not cosediment with MTs polymerized in the presence of taxol, NFs dephosphorylated with Escherichia coli alkaline phosphatase began to coprecipitate with MTs. The dephosphorylated NFs bound to MTs but not to the unpolymerized tubulin dimer. The binding was not observed in the presence of high salt or with MTs containing microtubule-associated proteins. The cosedimentation experiments using purified NF subunit proteins showed that the dephosphorylation induced binding of NFs to MTs was mediated by the largest subunit of NF (NF-H). Negative staining electron microscopy confirmed bindings of the dephosphorylated NFs and NF-H to MTs. Densitometric measurement of the bound and unbound NF-H after sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the binding of the dephosphorylated NF-H to MT was saturable and gave the following binding parameters. Approximately 1 mol of NF-H bound per 10 mol of tubulin dimer with a high affinity site (Kd = 3.8 x 10(-8) M) and per 16 mol of tubulin dimer with a low affinity site (Kd = 1.1 x 10(-7) M). PMID- 2254338 TI - The chemical synthesis of a gene coding for bovine pancreatic DNase I and its cloning and expression in Escherichia coli. AB - A gene coding for bovine pancreatic DNase I has been constructed from synthetic oligonucleotides. This gene has been cloned into a plasmid vector pDOC55 designed to allow very tight control of expression of potentially lethal proteins. Induction of protein synthesis from the gene yielded a peptide of molecular weight of approximately 31,000, consistent with DNase I. The yield of this protein from the pDOC55 construct (pAW5) was approximately 150 micrograms/liter of cell culture. Attempts to clone the gene into a less tightly controlled expression vector based on the tac-promoter (pKK223-3) were unsuccessful, presumably due to the expected lethality of the product. Mutagenesis of the gene to replace the active site histidine (His-134) in the protein with glutamine yielded a gene readily clonable into both expression systems. Yields of the mutagenized protein were approximately 6 micrograms/liter from a pDOC55 system and 20 mg/liter from a pKK223-3 system. The activity of the proteins were assayed using the Kunitz procedure and their cleavage selectivities by digestion of the Escherichia coli tyr T promoter. The recombinant native enzyme had both the same specific activity and DNA cleavage selectivity as the protein isolated from bovine pancreas using these two assays. The H134Q mutant had a specific activity of about 0.001% of the native protein but had an unaltered DNA cleavage selectivity. PMID- 2254339 TI - Effect of hypertension on fibronectin expression in the rat aorta. AB - Interactions between extracellular fibronectin and vascular cells are thought to influence the phenotype of those cells. To determine if changes in fibronectin expression accompany the phenotypic changes of vascular tissue characteristic of experimental hypertension, steady state mRNA levels for fibronectin were determined in aortae of normotensive and hypertensive rats. A 3-6-fold increase in fibronectin mRNA was observed in aortic tissue of hypertensive rats following 3 weeks of treatment with deoxycorticosterone and salt, whereas if rats were treated only with deoxycorticosterone or salt alone, no changes occurred. The changes were reversed by normalization of blood pressure. The increases observed were localized to aorta and not to the periaortic tissue. Angiotensin II infusion using osmotic minipumps also caused an increase in fibronectin expression. Age dependent increases in aortic fibronectin mRNA occurred in several rat strains, and the combined effects of hypertension and aging were greater than either variable alone. A clear distinction between the expression of fibronectin mRNA and that for collagen or tropoelastin were found in hypertensive and aging models. Aortic fibronectin was also increased in the hypertensive rats as determined by Western blot analysis. The findings indicate that elevation in blood pressure increases fibronectin expression in rat aorta and suggest that such changes may influence the aortic cellular responses to hypertension. PMID- 2254340 TI - Anaerobic biosynthesis of the manganese-containing superoxide dismutase in Escherichia coli. Effects of diazenedicarboxylic acid bis(N,N'-dimethylamide) (diamide). AB - Anaerobically grown Escherichia coli accumulate active manganese-containing superoxide dismutase (MnSOD) upon exposure to diamide. This induction requires de novo biosynthesis of MnSOD. Catalase, glutathione disulfide reductase, and glucose-6-phosphate dehydrogenase were also induced by diamide in anaerobic E. coli. A GSH-negative strain of E. coli did not produce MnSOD under anaerobic conditions and was as responsive to diamide as was the wild type strain. Diamide which had been prereduced, by incubation with GSH, was ineffective. NO3- plus paraquat, which elicits increased anaerobic biosynthesis of the MnSOD polypeptide, but not of active MnSOD, synergized with diamide in the induction of active MnSOD. A similar increase in the ability of diamide to cause anaerobic biosynthesis of active MnSOD was seen when the production of the MnSOD polypeptide was increased by isopropyl-beta-D-thiogalactopyranoside, in a strain bearing the MnSOD gene under the control of the tac promoter. These results are explained in terms of a dual action of diamide, i.e. at both the transcriptional and the maturational levels of biosynthesis of MnSOD. Oxidative inactivation of an Fe(II)-containing repressor and oxidative facilitation of insertion of manganese, in place of iron, into the nascent MnSOD polypeptide, are the postulated bases of this dual action. PMID- 2254341 TI - Structure and expression of the pulmonary surfactant protein SP-C gene in the mouse. AB - Genomic and cDNA clones encoding the murine pulmonary surfactant protein SP-C were isolated and sequenced to provide the primary amino acid sequence of the murine SP-C polypeptide and the structural organization of the SP-C gene locus. Murine SP-C is encoded by a single locus spanning approximately 3.2 kilobases of genomic DNA. The gene is composed of six exons and five introns, and its structure is closely related to the human SP-C gene. The primary transcript for the murine SP-C preprotein of Mr = 21,000 has an overall nucleotide identity of 80% with the coding sequence of the human precursor. The active airway peptide of 33-35 amino acids was even more closely related to the human SP-C airway peptide, sharing 95% identity at the amino acid level. The most significant structural difference between the murine and human SP-C genes was an increased size of the first intron in the murine SP-C gene. A single mRNA encoding murine SP-C of 0.8 kilobase was detected only in lung tissue, and SP-C mRNA was more abundant in neonatal and postnatal lung tissue than in fetal lung tissue. The nucleotide sequence of the promoter and 5'-flanking regions of the murine SP-C gene shared considerable identity with the human SP-C gene. Transgenic mice bearing a chimeric gene composed of the 5'-flanking and promoter regions of the human SP-C gene and the bacterial chloramphenicol acetyltransferase reporter gene were generated, demonstrating that lung-specific and developmental expression was conferred by these 5'-sequences. The chimeric gene was selectively expressed in preparations of respiratory epithelial cells, but was not expressed in alveolar macrophages isolated from the transgenic mice. The shared structural organization and developmental and tissue-specific expression of the SP-C gene between the mouse and human demonstrate considerable phylogenetic conservation of this gene and protein. PMID- 2254342 TI - Analysis of site-directed mutations in human pro-alpha 2(I) collagen which block cleavage by the C-proteinase. AB - We have used site-directed mutagenesis to obtain human pro alpha 2(I) cDNAs containing novel mutations designed to inhibit cleavage at the C-proteinase site. Deletion of six relatively conserved amino acids which surround the cleavage site did not interfere with assembly of the triple helix in transfected rat cells, but blocked cleavage of the constituent mutated chains by endogenous C-proteinase. Substitution for a conserved Asp, which forms part of the Ala-Asp bond cleaved by C-proteinase, also blocked cleavage by endogenous C-proteinase. The conserved Asp is, therefore, a necessary component of the C-proteinase cleavage site. Incubation in vitro with a purified mouse C-proteinase, confirmed both mutations to be resistant to cleavage by high concentrations of the physiologically relevant enzyme. Mutant pro alpha 2(I) chains, resistant to cleavage by C proteinase in culture media, were processed in cell layers by a different protease which cleaved telopeptide domains. Naturally occurring mutations at the C-proteinase site have not been described in human patients. The mutations characterized here, further define the C-proteinase cleavage site and provide reagents which may be informative when introduced into transgenic mice. PMID- 2254343 TI - The regulated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase requires a short-lived protein and occurs in the endoplasmic reticulum. AB - A chimeric gene consisting of the coding sequence for the membrane domain of the endoplasmic reticulum protein, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, fused to the coding sequence for the soluble enzyme, beta galactosidase of Escherichia coli, has been previously constructed. This fusion protein, HMGal, has been localized to the membrane of the endoplasmic reticulum of Chinese hamster ovary cells transfected with this chimeric gene, and its beta galactosidase activity has declined in the presence of low density lipoprotein (Skalnik, D. G., Narita, H., Kent, C., and Simoni, R. D. (1988) J. Biol. Chem. 263, 6836-6841). In this report, we demonstrate that the loss of beta galactosidase activity results from the accelerated degradation of the HMGal protein. Taking advantage of a fluorescence-activated cell sorter technique, we have selected transfected cells which express sufficient levels of HMGal to improve its immunodetection. Based on pulse-chase experiments, the half-life of HMGal is 6.0 h, and, in the presence of 20 mM mevalonate, the half-life declines 1.7-fold. Under these conditions, mevalonate accelerates the degradation of HMG CoA reductase in these cells 1.6-fold, from 8.4 h to 5.3 h, most probably by the same mechanism. This mevalonate-regulated degradation of HMGal is not due to a heteromeric association of HMGal with reductase, since the same effect has been observed in cells lacking the reductase protein. In addition, we demonstrate that inhibition of protein synthesis with cycloheximide abolishes the mevalonate dependent accelerated degradation of HMGal, in agreement with previous studies which have presented indirect evidence that a short-lived protein is essential for mediating the loss of HMG-CoA reductase activity. Finally, using brefeldin A, we show that the mevalonate-dependent accelerated degradation of HMGal may occur in the endoplasmic reticulum. PMID- 2254344 TI - Biosynthesis and properties of a further member of the small chondroitin/dermatan sulfate proteoglycan family. AB - Human osteosarcoma cells express a 78-kDa proteoglycan core protein to which an asparagine-bound oligosaccharide, O-glycosidically linked oligosaccharides and probably only a single chondroitin 6-sulfate chain of 29-kDa are bound. Prior to O-glycosylation, the N-glycosylated core protein exhibits a mass of 83 kDa. Upon digestion of the secreted proteoglycan with chondroitin ABC lyase a mature core protein with an apparent molecular mass of 106 kDa is obtained. Smaller amounts of core proteins of 101 and 115 kDa can be detected occasionally. The glycosaminoglycan composition and the relative molecular mass of the glycosaminoglycan chain distinguish this proteoglycan, tentatively named proteoglycan 100 (PG-100), from biglycan (small proteoglycan I) and decorin (small proteoglycan II) which are also expressed by osteosarcoma cells. An antiserum against PG-100 shows partial cross-reactivity with decorin, but in contrast to the latter proteoglycan it does not bind to type I collagen fibrils. PG-100 is not a unique product of osteosarcoma cells. It has also been found in the secretions of human skin fibroblasts. PMID- 2254345 TI - The stress response in Chinese hamster ovary cells. Regulation of ERp72 and protein disulfide isomerase expression and secretion. AB - Expression of the glucose-regulated proteins (GRPs), GRP78 and GRP94, is induced by a variety of stress conditions including treatment of cells with tunicamycin or the calcium ionophore A23187. The stimulus for induction of these resident endoplasmic reticulum (ER) proteins appears to be accumulation of misfolded or underglycosylated protein within the ER. We have studied the induction of mRNAs encoding two other resident ER proteins, ERp72 and protein disulfide isomerase (PDI), during the stress response in Chinese hamster ovary cells. ERp72 shares amino acid sequence homology with PDI within the presumed catalytic active sites. ERp72 mRNA and, to a lesser degree, PDI mRNA were induced by treatment of Chinese hamster ovary cells with tunicamycin or A23187. These results identify ERp72 as a member of the GRP family. Stable high level overproduction of ERp72 or PDI from recombinant expression vectors did not alter the constitutive or induced expression of other GRPs. High level overexpression resulted in secretion of the overproduced protein specifically but not other resident ER proteins. This suggests that the ER retention mechanism is mediated by more specific interactions than just KDEL sequence recognition. PMID- 2254346 TI - Identification of a DNA-binding site for the transcription factor GC2 in the promoter region of the p12 gene and repression of its positive activity by upstream negative regulatory elements. AB - Mouse secretory protease inhibitor p12 is significantly transcribed by the cells from the seminal vesicle, the coagulating gland, the ventral prostate, and to a lesser level by the pancreas. It is otherwise undetectable in every other tissue examined. To study the molecular mechanisms involved in this model of cell specific control of gene expression, we cloned fragments containing various lengths of the p12 promoter upstream of the CAT reporter gene. We demonstrated that p12 sequences from +34 to -108 relative to the CAP site can confer a constitutive level of CAT expression following transient transfection in non prostatic CV1 and GH4C1 cells. We identified within this minimal p12 promoter the cis-acting sequences needed to direct such a significant level of CAT expression. A DNA-binding site (p12.A) highly homologous to the rat growth hormone (rGH) sequence recognized by the trans-acting factor GC2 was identified between the TATA- and the double CAAT-box sequences from the p12 promoter. Using competition and mutation analysis, we provide evidence that the positively acting p12.A binding protein is likely to be the rGH GC2 transcription factor, suggesting that the same, or a very similar factor, regulates expression of both rGH and p12 genes. By further analysis of the p12 5'-flanking sequences, we demonstrated that plasmids including sequences from -109 to -843 can strongly repress the level of transcription directed by this minimal p12 promoter, providing evidence for the presence of cis-acting negative regulatory elements critical for the establishment of p12 gene extinction in non-prostatic cells. PMID- 2254347 TI - Kinetic intermediates in prothrombin activation. Bovine prethrombin 1 conversion to thrombin by factor X. AB - Two pathways are possible during the proteolytic formation of alpha-thrombin (alpha-IIa) from prothrombin (II) or prethrombin 1 (P1). One of the pathways, with prethrombin 2 or prethrombin 2 associated with fragment 2 (P2F2) as intermediates, has long been known to exist when activation is catalyzed by Factor Xa (Xa) alone. The second pathway, with meizothrombin or meizothrombin (des fragment 1) (MzIIa(-F1)) as intermediate, has been shown to exist when Factor Va and phospholipids are present with Xa. Until now, MzIIa(-F1) has not been detected in reactions catalyzed by Xa alone. In this study, we demonstrate that P1 activation by Xa alone occurs via both pathways, and we provide rate constants and kinetic equations for calculating the relative contributions of each of the pathways to the formation of alpha-IIa by Xa. Investigation of the initial rates of proteolytic cleavage of P2F2 and P1 by Xa alone indicated first order dependence on substrate concentration with no evidence of saturation of Xa with either substrate at concentrations as high as 200 microM. Apparent second order rate constants (kc/Km) of 113 +/- 9 M-1 s-1 for the formation of thrombin from P2F2 and 1,410 +/- 19 M-1 s-1 for the disappearance of P1 were determined at pH 7.5, 25 degrees C, 10 mM CaCl2, 0.15 M ionic strength. A two-step sequential first-order pathway employing these rate constants for thrombin activity production from P1 via P2F2 could not, however, account for the quantity of thrombin that was produced during the early stages of P1 activation. Addition of a parallel first-order reaction to produce thrombin activity from P1 independently of P2F2, tentatively identified as the formation of MzIIa(-F1), yielded progress curves in quantitative agreement with the experimental data. kc/Km for the parallel reaction was estimated to be 98 +/- 10 M-1 s-1. Independent determination of the second-order rate constant for the cleavage of isolated MzIIa (-F1), 15,000 +/- 420 M-1 s-1, indicated that MzIIa(-F1) could meet the kinetic requirements for an intermediate in the parallel activation pathway. The transient formation of MzIIa (-F1), as well as the generation of alpha-IIa, was directly demonstrated during activation of P1 by active site affinity labeling of the reaction products with a biotin derivative of D-Phe-Pro Arg chloromethyl ketone and visualization by semiquantitative Western blotting.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254349 TI - Hard decisions from soft data. PMID- 2254348 TI - A call to leadership. The role of orthopaedic surgeons in musculoskeletal outcomes research. PMID- 2254350 TI - The effects of exposure of articular cartilage to air. A histochemical and ultrastructural investigation. AB - The effects of exposure of articular cartilage to air and the potential for reversibility of the histological and ultrastructural changes that were produced by this exposure were investigated in the knee joint of the rabbit. After a medial parapatellar arthrotomy and lateral dislocation of the patella, the surface of the articular cartilage was exposed to air for one, two, and three hours in forty-five rabbits. Reversibility of the changes was assessed in fifteen rabbits after exposure of the cartilage to air for three hours, closure of the joint, and six weeks of recovery. Histochemical and ultrastructural changes were evaluated, with use of the contralateral non-exposed knee joint as a control. Depletion of glycosaminoglycans in the matrix of articular cartilage, as indicated by a loss of surface staining with toluidine blue, occurred after one hour of exposure to air. Ultrastructural changes occurred in chondrocytes throughout the full thickness of articular cartilage after one hour of exposure. Increases in the time of exposure to air resulted in more pronounced ultrastructural abnormalities in chondrocytes throughout the entire thickness of the articular cartilage, but there was no apparent irreversible cellular injury. Six weeks after arthrotomy, the chondrocytes had fully recovered from the changes that had been noted immediately after exposure to air, and they were devoid of degenerative changes. The cells showed ultrastructural evidence of increased metabolic activity in the nucleus and cytoplasm. In addition, the chondrocytes had partially restored the depleted glycosaminoglycans. PMID- 2254351 TI - Prerandomization: an alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee. AB - Possibly the greatest threat to the success of a randomized clinical trial is the inability to recruit an adequate number of subjects. Concern that the randomized clinical trial will adversely affect the physician-patient relationship is the most common reason for physicians' reluctance to enroll patients in such trials. We report a modification of a prerandomized design, first described by Zelen, which was implemented in a randomized clinical trial of arthroscopy for patients who had osteoarthrosis of the knee. The method was associated with a sixfold increase in the rate of accrual of patients as compared with the use of a classic randomization trial. We propose the design as a potential solution to the problem of recruitment of subjects, particularly for clinical studies. PMID- 2254352 TI - The effect of intravenous fixed-dose heparin during total hip arthroplasty on the incidence of deep-vein thrombosis. A randomized, double-blind trial in patients operated on with epidural anesthesia and controlled hypotension. AB - Heparin was given in fixed doses intravenously during unilateral primary total hip-replacement operations in a prospective, double-blind trial to assess the effect on the incidence of deep-vein thrombosis. One hundred and fifty patients were randomly assigned to one of two groups before the operation. Twenty-four patients were excluded from the study, leaving 126 patients. Group I consisted of sixty-six patients who received saline solution intravenously, and Group II comprised sixty patients who received heparin. All patients had epidural anesthesia with controlled hypotension. Fixed doses of heparin were administered five minutes before the operative incision was made and every thirty minutes throughout the operation. Mean arterial pressures were maintained at between fifty and sixty millimeters of mercury in all patients. Ascending venography was done on the seventh day after the operation. The incidence of deep-vein thrombosis was 24 per cent (sixteen of sixty-six patients) in Group I and 8 per cent (five of sixty patients) in Group II; the difference is significant (p = 0.03). The intraoperative loss of blood averaged 220 +/- 79 milliliters in Group I compared with 269 +/- 109 milliliters in Group II. An average of less than one unit of blood was transfused for each patient in each group. Postoperatively, there was no difference between the groups with regard to the amount of drainage that was collected in a Hemovac device or the values for hematocrit. PMID- 2254353 TI - Open fractures of the tibia in children. AB - Forty-one children who had forty-two open fractures of the tibial metaphysis or diaphysis were studied retrospectively. Twelve fractures were Type I; eighteen, Type II; six, Type IIIA; four, Type IIIB; and two, Type IIIC, according to the classification of Gustilo et al. All fractures were irrigated and debrided, and antibiotics were given for a minimum of forty-eight hours after the injury. Twenty fractures were initially treated with external fixation and twenty-two, with immobilization in a plaster cast. Three patients had an early infection of the wound, one of which was associated with osteomyelitis; all were successfully treated. The average time to healing of the fracture was five months (range, two to twenty-one months). The time to union was related to the severity of the soft tissue injury, the pattern of the fracture, the amount of segmental bone loss, the occurrence of infection, and the use of external fixation. There were six delayed unions. Four patients had an angular malunion of more than 10 degrees, which spontaneously corrected in three. One patient who had a proximal metaphyseal-diaphyseal segmental fracture had a progressive valgus deformity. Four patients who had a severe fracture that was treated with external fixation had more than one centimeter of tibial over-growth. There were no amputations. The incidences of compartment syndrome, vascular injury, infection, and delayed union were similar to those reported for open tibial fractures in adults. PMID- 2254354 TI - Total hip arthroplasty with cement. A long-term radiographic analysis in patients who are older than fifty and younger than fifty years. AB - The long-term performance of a total of 712 Charnley and STH prostheses was evaluated as a function of the patient's age (older than fifty years or younger than fifty years) and of the underlying disease (osteoarthrosis, rheumatoid arthritis, or avascular necrosis). In patients who were older than fifty years, there were lower incidences of continuous cement-bone radiolucency about the acetabular component (p = 0.04), wear of the polyethylene acetabular cup (p = 0.03), and resorption of the calcar (p = 0.03). However, larger percentages of younger patients had rheumatoid arthritis or avascular necrosis. In the cohort of patients who had osteoarthrosis, the performance of the prosthesis did not differ significantly between older and younger patients; therefore we attributed the differences that were observed to the disease--that is, to rheumatoid arthritis or avascular necrosis. PMID- 2254355 TI - Function after amputation, arthrodesis, or arthroplasty for tumors about the knee. AB - We studied the function of twenty-two patients who had had a malignant skeletal tumor adjacent to the knee. An above-the-knee amputation was done in seven; a resection arthrodesis, in nine; and a replacement arthroplasty, in six. The patients all walked at a similar speed (sixty-one to sixty-six meters per minute), which is slower than normal (eighty meters per minute). They all walked with comparable efficiency at three velocities: the mean consumption of oxygen was 0.210 milliliter per kilogram of body weight per meter at free velocity, 0.215 milliliter per kilogram of body weight per meter when they walked 25 per cent faster, and 0.211 to 0.240 milliliter per kilogram of body weight per meter when they walked 50 per cent faster. The three groups of patients and a normal control group consumed oxygen at similar rates. The patients who had had an amputation were very active, and they were the least worried about damaging the affected limb, but they had difficulty walking on steep, rough, or slippery surfaces. The patients who had had an arthrodesis had a more stable limb and performed the most demanding physical work and recreational activities, but they had difficulty sitting. The patients who had had an arthroplasty led sedentary lives and were the most protective of the limb, but they were the least self conscious about the limb. PMID- 2254356 TI - The arterial vascularization of the humeral head. An anatomical study. AB - In twenty-nine specimens from fresh cadavera, we performed an anatomical study of the arteries of the humeral head to determine their intraosseous distributions. A radiopaque suspension was injected into the anterior circumflex, posterior circumflex, suprascapular, thoracoacromial, or subscapular artery and then the specimens were dissected and were analyzed macroscopically, and radiographs were made in three mutually perpendicular projections. In addition, sixteen of the specimens were cut into four-millimeter slices and were studied microradiographically. The humeral head was shown to have been perfused by the anterolateral ascending branch of the anterior circumflex artery in all specimens. That vessel ran parallel to the lateral aspect of the tendon of the long head of the biceps and entered the humeral head where the proximal end of the intertubercular groove met the greater tuberosity. When the intraosseous (terminal) part of the anterolateral branch, the so-called arcuate artery, had been perfused, almost the entire epiphysis was radiopaque. The posterior circumflex artery vascularized only the posterior portion of the greater tuberosity and a small posteroinferior part of the head. Anastomoses between the different arteries were abundant, but vascularization of all of the humeral head was possible only through the anterolateral branch of the anterior circumflex artery. PMID- 2254357 TI - Organization of intrathecal nerve roots at the level of the conus medullaris. AB - The three-dimensional organization of the spinal nerve roots at the level of the conus medullaris has not been described previously, to our knowledge. In this study, we used a newly developed technique of in situ fixation and embedding to define the cross-sectional anatomy at the level of the conus medullaris in ten fresh human cadavera. A highly organized overlapping pattern of nerve roots was demonstrated in all specimens. The nerve roots form a peripheral rim around the spinal cord at the levels of the tenth and eleventh and the eleventh and twelfth thoracic intervertebral discs. More caudally, the cord diminishes in size and the nerve roots predominate. The most cephalad roots lie laterally, with the motor roots ventral to their sensory counterparts. The more caudad roots overlap toward the midline, and the motor and sensory portions of each root are separated by spinal cord tissue. An intricate web of arachnoid membrane holds the nerve roots in a fixed relationship to each other. PMID- 2254358 TI - Hazards of internal fixation in the treatment of slipped capital femoral epiphysis. AB - We reviewed the records of 202 patients (308 hips) in whom a slipped capital femoral epiphysis had been fixed with pins or screws. A serious complication that was directly related to the use of internal fixation developed in eighty hips (26 per cent). The rate of complications in the 202 patients was 40 per cent. In thirty-six (18 per cent) of the 202 patients, an additional procedure was done to correct a pin-related complication. Forty-one hip joints had been penetrated by a pin. Other complications included avascular necrosis (fourteen hips), chondrolysis (nine), fracture (one), infection (one), further slippage (one), sciatic-nerve injury (one), and breakage of a screw (eight). Ways of decreasing the incidence of complications of fixation were explored. PMID- 2254359 TI - Osteoarthrosis and congenital dysplasia of the hip in family members of children who have congenital dysplasia of the hip. AB - Four hundred and eight siblings, parents, and grandparents of seventy-eight children from the New England area who had congenital dysplasia of the hip were evaluated, by clinical examination and by measurements of the acetabulum on pelvic radiographs, for the signs and sequelae of congenital dysplasia of the hip. Six siblings and four mothers (representing seven of seventy-eight families) had been diagnosed with congenital dysplasia of the hip during childhood. The other ninety-one siblings were asymptomatic and had no radiographic evidence of dysplasia of the hip. In the adults in these families, acetabular coverage (as measured by the center-edge angle of Wiberg) was no different from that in the control subjects. There was no difference between the study group and the control subjects in the prevalence of osteoarthrosis of the hip or of osteoarthrosis that could be considered secondary to congenital dysplasia of the hip. The results indicate that children born to families that have a history of congenital dysplasia of the hip have a greater prevalence of this problem compared with the general population, but also that examinations of the hip in newborns are effective in detecting congenital dysplasia of the hip in such families. The greater prevalence of congenital disease of the hip among the siblings and mothers in these families is consistent with a multifactorial inheritance. The fact that acetabular development in the family members who did not have congenital dysplasia of the hip was no different from that in the control subjects suggests that acetabular dysplasia, rather than being an inherited abnormality, is secondary to subluxation or dislocation. PMID- 2254360 TI - Subtle injuries of the Lisfranc joint. AB - In fifteen patients, a subtle injury of the Lisfranc joint (tarsometatarsal articulation) was found. The lesion was defined as a diastasis of two to five millimeters between the bases of the first and second metatarsals, as seen on anteroposterior radiographs. There often was a long delay between injury and diagnosis. Eight patients were treated with a below-the-knee cast only, three had treatment with a cast and then tarsometatarsal arthrodesis, two had no initial treatment but later had arthrodesis, and two had open reduction and internal fixation. The duration of follow-up ranged from two to thirteen years after the diagnosis. There was no correlation between the severity of the diastasis and the patient's functional result. Marked disability and pain persisted in seven patients, and six of them had flattening of the longitudinal arch. Maintenance of the longitudinal arch usually was associated with a better functional outcome. When a patient has a subtle injury of the Lisfranc joint, weight-bearing lateral radiographs of both feet are needed to identify flattening of the longitudinal arch. Such radiographs should be made routinely in the evaluation of all injuries of the foot that may involve the Lisfranc joint. PMID- 2254361 TI - Shielding of the patient's gonads during intramedullary interlocking femoral nailing. AB - Levels of exposure to radiation were recorded at sixty sites in fifteen patients during intramedullary interlocking femoral nailing. Radiation film dosimeters were placed at four gonadal sites on each subject. A standard male-gonad cup or a pelvic drape of 0.5-millimeter-thick lead-equivalent was put in place to shield the gonads. A second set of four dosimeters was placed external to the shield to approximate unprotected exposure. The total duration of the fluoroscopy averaged five minutes (range, thirty seconds to fourteen minutes). The total exposure to radiation external to the shield was 35 +/- 34 millirems at the male gonadal sites and 17 +/- 11 millirems at the female gonadal sites. With use of the gonadal shield, exposure to radiation was not measurable in thirteen of the fifteen patients. The differences between the exposures of the shielded and unshielded sites to radiation were statistically significant (p less than 0.001). The highest level of gonadal exposure was found with the treatment of proximal femoral fractures and with the use of statically locked nails. Regardless of the conditions, and for all types of fractures and locations, our results demonstrated that gonadal shielding is justified. PMID- 2254362 TI - Aspiration of hematomas with liposuction apparatus. A technical note. PMID- 2254363 TI - Failure of acetabular autogenous grafts in total hip arthroplasty. Increasing incidence: a follow-up note. AB - We reported previously on the application of an autogenous femoral-head graft to the acetabulum during total hip arthroplasty for compensation of marked osseous deficiency in patients who had arthritis secondary to severe congenital dysplasia or dislocation of the hip. An average of seven years postoperatively, the graft seemed to have been a successful adjunct to the arthroplasty. Five years later, to assess our long-term results, we reviewed the findings in the same forty-six hips (thirty-seven patients) that we had studied previously. An average of 11.8 years after the total replacement and use of the autogenous femoral-head graft, nine hips (20 per cent) needed a second operation because the acetabular fixation had failed. Two had had a resection arthroplasty and seven, a complex revision. In one additional hip, a resection arthroplasty was done for infection that had developed after operative reattachment of the greater trochanter. In twelve of the remaining thirty-six hips, there was definite radiographic evidence of acetabular loosening. Thus, the total incidence of loosening of the acetabular component was 46 per cent (twenty-one hips). The average time from the index operation to the first definite radiographic evidence that the fixation had failed was 6.4 years (range, 2.9 to 12.7 years). While we recognize that application of a bulk autogenous graft to the acetabulum is useful when the acetabular bone stock is extremely deficient, we no longer recommend the use of bulk corticocancellous autogenous grafts in other situations. PMID- 2254364 TI - The Van Nes tibial rotationplasty. A functionally viable reconstructive procedure in children who have a tumor of the distal end of the femur. AB - Twelve patients who had a malignant tumor of the distal end of the femur were treated with a Van Nes tibial rotationplasty. The survival rates were comparable with those for above-the-knee amputees and patients who had an endoprosthetic replacement. The results of functional testing showed that these patients performed as well as those who had endoprosthetic replacement and better than those who had above-the-knee amputation. Rotationplasty is therefore a favorable alternative to amputation or endoprosthetic replacement, either as a primary or as a salvage procedure. PMID- 2254365 TI - Dissociation of acetabular components after total hip arthroplasty. Report of four cases. PMID- 2254366 TI - Staged reimplantation of a total hip prosthesis after infection with Candida albicans. A report of two cases. PMID- 2254367 TI - Subtrochanteric pathological fracture of both femora secondary to malignant pheochromocytoma. A case report. PMID- 2254368 TI - Histology of bone after parathyroid adenectomy. A case report. PMID- 2254369 TI - Muscle performance evaluation in orthopaedic practice. PMID- 2254370 TI - Mechanical considerations for the syndesmosis screw. A cadaver study. PMID- 2254371 TI - Quantitative structure-activity relationships (QSAR) and molecular modelling in cancer research. PMID- 2254372 TI - Androgen-linked alkylating agents: biological activity in methylnitrosourea induced rat mammary carcinoma. AB - This article gives a comprehensive survey on the anticancer activity of nitrosoureas linked to steroidal androgens in methylnitrosourea (MMU)-induced rat mammary carcinoma. cis-Androsterone, testosterone, 19-nortestosterone and 5-alpha dihydrotestosterone were used as carrier hormones and were linked to various cytotoxic N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl] (CNC)-aminoacids and to N-(2 hydroxyethyl)-N'-(2-chloroethyl)-N'-nitrosourea hemisuccinate (HECNU hemisuccinate). In the MNU-model used esters of dihydrotestosterone (DHT) invariably were more active and less toxic than those of testosterone, nortestosterone and cis-androsterone. Within the DHT esters of CNC-aminoacids those of CNC-glycine, CNC-methionine and CNC-alanine showed the highest antineoplastic activities and superiority compared with equimolar dosages of their unlinked mixtures. Additionally, CNC-alanine-DHT ester had the highest therapeutic ratio of all agents investigated. HECNU-hemisuccinate-DHT ester, on the other hand, achieved even higher antitumor activity at the optimal dose but had a narrower therapeutic ratio. No obvious correlation between antineoplastic efficacy and receptor binding affinity could be demonstrated, but, to be active, a conjugate apparently had to have some receptor binding affinity for both androgen and progesterone receptors. The results obtained indicate that linking antineoplastic agents to transport molecules with affinity to steroid receptors is a highly promising approach to obtain drugs with specific activity in steroid receptor containing tumors. PMID- 2254373 TI - In vitro and in vivo anticancer activity of mitozolomide and sparsomycin in human tumor xenografts, murine tumors and human bone marrow. AB - The colony formation in agar of human tumor xenografts, of murine tumors and of human bone marrow was used as a test system to determine the in vitro activity of the two novel cytostatic agents, mitozolamide and sparsomycin. Mitozolomide was additionally studied in vivo in nine human tumor xenografts. The comparison of in vitro/in vivo activity allows an assessment of the relevant in vitro dose based on in vivo pharmacological behavior of a compound. Both compounds showed clear dose/response effects in vitro. A dose of 3 micrograms/ml mitozolomide, given by continuous exposure, was active (colony number of test less than 30% of the control group) in 12/42 (29%) human tumor xenografts as well as in the four murine tumors, P388, L1210, B16 melanoma and colon carcinoma 38, whereas the two human bone marrows showed no significant suppression of the ability to form colonies in culture. The comparison of in vitro with in vivo activity suggests that the in vitro dose of 3 micrograms/ml corresponds best to the activity observed in animal experiments. The highest activity was observed in small-cell cancer of the lung (4/5), followed by melanomas (2/7) and non-small-cell cancer of the lung (2/9). Furthermore, activity was found in a cancer of the large bowel, stomach, breast and in one sarcoma. In the treatment of nine human tumor xenografts growing subcutaneously in nude mice, mitozolomide effected a complete or partial remission in 6 out of 9 tumors. In comparison to standard drugs mitozolomide is one of the most effective compounds in these tumors. These data indicate that mitozolomide possesses potent broad-spectrum activity in human tumor xenografts. Sparsomycin (0.1 micrograms/ml, continuous exposure) was active in 11/46 (24%) human tumor xenografts and in 4/5 of the murine tumors, whereas the colony-forming capacity of four human bone-marrows showed no inhibition, suggesting that this dose level may be the relevant in vitro dose. However, the high in vitro activity in murine tumors is incompatible with the in vivo activity. In mice the only responsive tumor was leukemia P388, whereas the L1210, B16 melanoma and colon carcinoma 38 were resistant. At the dose level of 0.03 microgram/ml only 3/30 (10%) of the human tumor xenografts were sensitive. In an earlier clinical phase I study the dose-limiting adverse effect was eye toxicity and not bone-marrow suppression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254374 TI - New functional cell-culture approach to pulmonary carcinogenesis and toxicology. AB - Modern pulmonary toxicology (including lung carcinogenesis) has, to assist its rapid development, constantly incorporated the knowledge obtained through cell and tissue-culture studies. While this has been carried out in rather a passive manner until quite recently, the currently necessary multi-disciplinary approach increasingly requires more active involvement of cell/tissue-culture techniques in this area. Our understanding in this regard is that one of such requirements is to establish a cell-culture system consisting of a single population of possible target cells for certain classes of hazardous inhalants. In addition, such target cells in culture should be able to function in a manner as closely resembling the situation in vivo as possible. In view of the culture techniques presently available, this requirement is probably too ideal to be met immediately. Nevertheless, efforts have been made in the last decade to achieve functioning cultures of Clara cells, type II pneumocytes or small mucus granule cells (SMGC), using undifferentiated cells obtained from animal and human fetuses. This attempt forms a sharp contrast to the usual approach, in that while the latter tries to keep the functions of adult cells in an already differentiated state, the former aims at inducing functional differentiation in undifferentiated cells by manipulating culture conditions. In carrying out these efforts, we have shown clear evidence that the type II pneumocytes and Clara cells induced in vitro are closely cognate and share a common precursor cell in culture, and that SMGC are at a pre-stage of differentiation to Clara cells. We have also shown an induced capacity for xenobiotic activation and conjugation in SMGC in culture. Our next plan is to prove similar activity (of mixed-function oxidase) in Clara cells and type II pneumocytes induced to differentiate in culture. PMID- 2254375 TI - Tobacco-specific nitrosamines in Canadian cigarettes. AB - Twenty-five brands of Canadian commercial cigarettes were analyzed for tobacco specific nitrosamines (TSNA) in tobacco and in mainstream smoke as well as for nitrate in tobacco. Preformed N'-nitrosonor-nicotine (NNN) in the tobacco ranged from 265 ng to 979 ng/cigarette, preformed 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) ranged from 465 ng to 878 ng/cigarette. The mainstream smoke concentration for NNN was between 5 ng and 39 ng/cigarette and for NNK between 5 ng and 97 Ng/cigarette. The nitrate levels were between 0.3 mg and 3.4 mg/cigarette. The NNK levels in tobacco and in mainstream smoke were higher than the NNN levels, which is typical for Virginia-type cigarettes. Based upon the average mainstream smoke concentration of the three most popular Canadian cigarette brands, an average TSNA delivery for 20 cigarettes of 0.7 micrograms NNN and 1.7 micrograms NNK can be calculated, which is less than the average for West German cigarettes. The results of this investigation demonstrate that there seems to be a good correlation between the TSNA and tar deliveries in mainstream smoke. However, no correlation between the level of preformed TSNA in tobacco and the tar delivery in mainstream smoke could be observed. It is demonstrated that the good correlation between the tar and TSNA deliveries in mainstream smoke can only be attributed to the unusual good correlation between the tar delivery and the ventilation ratio. For the cigarettes investigated, which seemed to be Virginia-type cigarettes, with few exceptions, the ventilation ratio had a much higher influence on the mainstream smoke concentration than the level of preformed TSNA in tobacco. PMID- 2254376 TI - N-nitrosamino phosphates are unlikely transport forms for activated nitrosamines. AB - Some of the target organs for nitrosamine carcinogenicity have a low activating capacity but many carcinogenic nitrosamines can be activated in the liver. Conjugates, such as phosphates, are chemically accessible reaction products of 1 OH-nitrosamines, and are either potential detoxication products or potential transport forms for activated nitrosamines. 14C-labeled 1-(N-ethyl-N nitrosamino)ethyl phosphate was tested for its ability to enter primary rat hepatocytes but no uptake was detectable. No uptake was observable into fibroblasts and human leukocytes. N-Nitrosomethylbenzylamine is efficiently 1-C hydroxylated by hepatocytes but the corresponding 1-C-phosphate was detectable neither in the cells nor in the surrounding medium. N-Nitrosamino-1-phosphates, unlike 1-glucuronides, therefore, do not seem to be important for nitrosamine toxicokinetics. PMID- 2254377 TI - Significance of exposure to benzene and other toxic compounds through environmental tobacco smoke. AB - In order to assess the uptake of benzene from environmental tobacco smoke (ETS) and to estimate its contribution to the total body burden of benzene observed in non-smokers, two experimental studies have been conducted. Controlled exposure to high levels of ETS equivalent to 10 ppm CO for 9 h and 20 ppm for 8 h resulted in a nonsignificant increase in blood benzene levels and a significant increase in exhaled CO, COHb and cotinine in serum and urine. The slightly rising blood concentration of benzene following experimental ETS exposure was paralleled by an increased exhalation of benzene and aromatic hydrocarbons and in contrast to blood levels, this increase was significant. The blood levels of benzene obtained during exposure were comparable to those observed at the time of admission to the laboratory, when biomarkers of ETS uptake, e.g. cotinine in serum and urine, were at the limit of detection, thus demonstrating that these background levels were not from ETS exposure. No difference in the urinary excretion of phenol, the main metabolite of benzene, was found during the experimental periods. The background levels of urinary phenol in unexposed nonsmokers were rather high, demonstrating that phenol excreted in urine must be formed from several endogenous and exogenous precursors. In the light of our findings it is highly questionable whether exposure to benzene from ETS under real life conditions poses a cancerogenic risk to the general population, which is measurable today or in the future by toxicological or epidemiological methods. PMID- 2254378 TI - Alterations in dimethylnitrosamine-induced lethality and acute hepatotoxicity in rats during dietary thiamin, riboflavin and pyridoxine deficiencies. AB - The effects of dietary thiamin, riboflavin and pyridoxine deficiencies on dimethylnitrosamine-induced lethality and hepatotoxicity were investigated in the rat. Development of deficiencies was monitored by growth rate, food intake, ratio of liver weight to body weight and the biochemical parameters (thiamin diphosphate effects for thiamin deficiency, glutathione reductase activity coefficient for riboflavin deficiency and erythrocyte glutamate-oxaloacetate transaminase activity for pyridoxine deficiency). Thiamin deficiency slightly increased the acute toxicity of dimethylnitrosamine as observed by the lowering of the LD50 dose and the greater increase in the serum glutamate-oxaloacetate transaminase and serum glutamate-pyruvate transaminase levels. Riboflavin deficiency, on the other hand, slightly increased the LD50 dose of dimethylnitrosamine and resulted in less dimethylnitrosamine-induced damage to the liver. Pyridoxine deficiency did not affect the lethal dose nor significantly alter the transaminases levels. PMID- 2254379 TI - Comparative carcinogenicity of cigarette mainstream and sidestream smoke condensates on the mouse skin. AB - The direct carcinogenic effects of sidestream (SS) and mainstream (MS) smoke condensates of a filtered commercial brand of blond cigarettes were compared using a lifetime mouse skin tumorigenicity assay on female NMRI mice. Each cigarette was smoked by a smoking machine under the standard conditions, and the separately collected SS and MS smoke condensates were extracted with acetone/methanol as described elsewhere. These were tested for carcinogenicity on an area of 1-1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose (5, 10 or 15 mg) twice a week, for only 3 months. No substance was used as promoter or as an additional initiator of carcinogenicity. No statistically significant difference was found when the life spans of MS treated and untreated animals were compared. In contrast, the life spans of SS treated mice were significantly (P less than 0.01) shorter than those of MS treated animals or those of all three negative control groups together. The observed carcinogenic effects were based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, 3 developed skin lesions but no tumours. Of 210 MS-treated mice (effective number, 177), 7 developed tumours (4 malignant and 3 benign) and 35 had a uniform type of precancerous skin lesions. The numbers of tumours or lesions were not increased dose-dependently. Of 210 SS-treated animals (effective number, 182), 30 developed tumours (16 malignant and 14 benign) and 56 had a uniform type of precancerous skin lesion. The initiation of these latter lesions was found to be dose-dependent (P less than 0.001). The SS-treated animals developed two to six times more skin tumours than the MS-treated mice. Comparing the negative controls with the MS- or SS-treated animals, the overall carcinogenic effect observed was statistically significant. Comparing the MS- with SS-treated animals, the overall carcinogenic effect of SS was much higher than that of MS (P less than 0.001). PMID- 2254380 TI - Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance. AB - In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1%), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the uterine horn of aged rats. Histologically, most demonstrated glandular structures, consisting of cuboidal or columnar cells with weak eosinophilic or basophilic cytoplasm and large nuclei. In about half of the animals with adenocarcinomas, metastasis to remote organs such as the lung was observed. Histological examination of the ovary and vaginal epithelium revealed ovarian cysts, atrophy of the ovary and cornification of the vaginal epithelium more frequently in rats with endometrial carcinomas than in animals without tumors. These findings indicate that adenocarcinoma development in Donryu rats is associated with endocrine imbalance [increased serum estrogen: progesterone (E2:P)ratios]. By comparative investigation of strain differences, it was confirmed that irregular estrous cycles began earlier with higher incidence in Donryu rats than in F344 rats, a low-incidence strain. Histological findings of the ovary and vaginal epithelium also suggested relatively increased estrogen levels in Donryu rats compared to F344 rats. Estimated plasma values of gonad steroids showed that the E2:P ratio in Donryu rats at 12 months of age was about five times that in F344 rats. These results therefore indicate that hormone imbalance, particularly an increased E2:P ratio, may play an important role in the spontaneous occurrence of endometrial adenocarcinoma in Donryu rats. PMID- 2254381 TI - Effect of methotrexate on the release of prostaglandins E2, D2, and I2 from small intestine in the rat in vivo. AB - Intraperitoneal administration of methotrexate in a single dose of 40 mg/kg induces fluid accumulation in the small intestine of rats, significantly increasing jejunal PGE2 formation and simultaneously the amounts of PGE2 in the intestinal contents in vivo. Concomitantly, jejunal PGD2 and 6-keto-PGF1 alpha generation and the amounts of these prostaglandins in the intestinal contents were significantly lowered. However, PGD2 and 6-keto-PGF1 alpha jejunal release, and the amounts of these prostaglandins found in the intestinal contents, were already low after a sublethal dose (4 mg/kg) of methotrexate, whereas the jejunal release as well as the amounts in the intestinal contents of PGE2 were not altered. Fluid accumulation, the amounts of prostaglandins in the intestinal contents and jejunal release of prostaglandins are significantly inhibited by indomethacin. The increased jejunal synthesis of PGE2, with its enteropooling effect, may play a significant role in methotrexate-induced diarrhea in rats. PMID- 2254382 TI - Adriamycin uptake and metabolism in organotypic culture of A549 human adenocarcinoma cells according to the exposure time. AB - In organotypic cultures (nodules) of A 549 human lung adenocarcinoma cells, the long-term cytotoxicity of Adriamycin is strongly improved by shortening the exposure time to the drug. In order to gain insight into the mechanisms of Adriamycin toxicity in this system, we have examined the drug uptake, retention and metabolism by fluorescence microscopy and HPLC analysis. A 549 nodules efficiently metabolize Adriamycin, two major metabolites, adriamycinol and an aglycone derivative, as yet chemically unidentified, are formed and efficiently excreted. Kinetic data show that a long exposure to Adriamycin triggers its efflux from both the nucleus and the cytoplasm while stimulating its metabolism. Therefore, a long exposure time to the drug appears to trigger a process of cellular detoxification by favouring its excretion from the cells via increased metabolism. PMID- 2254383 TI - Descriptive epidemiology of thyroid cancer in the Swiss Canton of Vaud. AB - Although substantial decreases have been recorded, age-standardized mortality rates from thyroid cancer in Switzerland are still the highest in Europe in men (0.9/100,000), together with those from Austria, and the third highest (1.0/100,000) in women. Detailed analysis of 308 new cases registered between 1974 and 1987 in the Swiss Canton of Vaud revealed an overall incidence rate of 1.36/100,000 men (world standard) in 1974-1980 and of 1.74/100,000 in 1981-1987. Corresponding values for women were 4.28 and 4.51, respectively. Thus, women constituted the majority of all cases (76%). Papillary carcinoma was the most frequent histological type (53%) followed by follicular (27%), undifferentiated (5%) and medullary (2%); other morphologies and clinical tumours accounted for 13% of the whole series. In both sexes, most of the apparent increase over the calendar period was restricted to the papillary type. Overall 5- and 10-year survival rates were 71% and 57%. When various factors were introduced in a Cox proportional-hazard model, young age at diagnosis (hazard rate for greater than or equal to 65 years vs less than 45 = 14.7; 95% confidence interval = 7.5-29.1) and good histological differentiation (hazard rate for papillary and follicular vs undifferentiated = 0.4) emerged as strong favourable and independent prognostic factors. The reduced hazard rate for women, other factors being equal, was of borderline significance (0.7, 95% confidence interval = 0.5-1.0), whereas no significant difference was observed between follicular and papillary carcinomas, and calendar periods of diagnosis. PMID- 2254384 TI - Long-term application of vindesine: toxicity and tolerance. AB - This is a report on 14 patients receiving vindesine continuously for between 1 and 7 years. Total vindesine doses ranged from 86 mg to 454 mg and the longest treatment duration was 2564 days. Although there was no patient without a transient acute or subacute toxicity, no unequivocal signs of long-term toxicity have been observed so far. Greater caution must be given to the concomitant use of higher radiation doses and vindesine, since local reactions were more pronounced especially at the lung. The drug seems to be tolerated for longer periods without major or cumulative toxicity, which makes it suitable for use in the adjuvant setting, for instance, or within an antimetastatic approach. PMID- 2254385 TI - Intramural myocardial infarction under combined radiochemotherapy of an oesophageal carcinoma. PMID- 2254386 TI - Renaissance of gas chromatography-time-of-flight mass spectrometry. Meeting the challenge of capillary columns with a beam deflection instrument and time array detection. AB - This report describes the use of a unique beam deflection time-of-flight mass spectrometer to address some of the demands made on mass spectrometry by new developments in high-resolution capillary column gas chromatography. An integrating transient recorder is used in combination with this beam deflection time-of-flight instrument to apply the concept of time array detection in capturing all of the mass spectral information available from the ion source, thereby greatly enhancing the signal-to-noise ratio quality of the mass spectral data. The applicability of the time array detection approach to gas chromatography-mass spectrometry is demonstrated in the context of an analysis of the standard Grob mixture for assessing performance of capillary column chromatography. During analysis of the Grob mixture by gas chromatography-mass spectrometry, mass spectra were recorded at a rate of 20 scan files per second. The data indicate that this rate of mass spectral scan file generation is adequate to provide a suitable data base for reconstruction of the chromatographic profile. In addition, the effective scan rate is high enough that there is no distortion in the relative peak intensities throughout the individual mass spectra of components regardless of the relatively high dynamic changes in partial pressure of the analyte as reflected by the sharp peaks in the chromatographic profile. The experimental results indicate that the beam deflection time-of-flight mass spectrometer can provide mass spectra at a scan file generation rate much higher than that possible with the conventional quadrupole or magnetic sector mass spectrometer, but at comparable detection limits. PMID- 2254387 TI - Effects of the pre-column in automated on-column injection capillary gas chromatography. AB - In this work, we investigated the effects of pre-columns and press-fit connectors on automated cold on-column injection capillary gas chromatography. Verapamil, a calcium channel blocking vasodilator used in the treatment of angina, arrhythmias and hypertension, and norverapamil, an active metabolite, were used as model compounds in these investigations. Wide-bore fused-silica tubing deactivated with OV-1701-vinyl was also studied with respect to its suitability as pre-column material. The detector response of verapamil versus an internal standard was consistent at micrograms/ml and ng/ml levels, while that of norverapamil decreased with the amount injected. However, the decrease in response of norverapamil appeared to be unrelated to the presence of a pre-column or press fit connector in the chromatographic system. PMID- 2254388 TI - High-performance size-exclusion chromatography of porcine colonic mucins. Comparison of Bio-Gel TSK 40XL and Sepharose 4B columns. AB - A high-performance size-exclusion chromatography (HPSEC) method was developed for the separation of porcine colonic mucins using a Bio-Gel TSK 40XL HPSEC column (300 mm x 75 mm). In addition, porcine gastric and bovine submaxillary mucin preparations were used to describe more fully the separation characteristics of the HPSEC column. For comparison, the same preparations were also separated using a Sepharose 4B column (100 cm x 2.6 cm). The colonic and gastric mucins eluted in the void volume (V0) of both columns. Bovine submaxillary mucin was in the elution volume (Ve) of both columns. Analytical HPSEC of fractions (V0 and Ve) of the various preparations obtained by Sepharose 4B chromatography exhibited retention times identical to those for fractions obtained by HPSEC. After separation by both methods, purified mucins were obtained by CsCl2 density gradient ultracentrifugation; analytical HPSEC profiles, protein contents, and monosaccharide compositions of both gastric and colonic mucins from either column were similar. The HPSEC method, however, is ideally suited to separate microgram to milligram quantities of colonic mucin preparations quickly: 2 to 4 h, compared with 24 to 30 h for the Sepharose 4B method. PMID- 2254389 TI - Derivatization-liquid chromatographic assay of chloroacetaldehyde in biological samples. PMID- 2254390 TI - [Tumor cell and stroma interaction]. PMID- 2254391 TI - [Clinical evaluation of cervical myelopathy by means of short latency somatosensory evoked potentials]. AB - Short latency somatosensory evoked potentials (sSEP) were recorded in 47 patients with cervical myelopathy, and the results obtained were compared with clinical symptoms and changes in the waveform of evoked spinal cord action potentials. sSEPs were classified into three types according to the changes in the waveform: type 1; normal waveform (18 cases), type 2; longer latency or reduced amplitude of sSEP (20 cases), type 3; no observable sSEP (9 cases). Decompression surgery on the spine was performed in 29 cases (including 9 type 1 cases, 13 type 2 cases and 7 type 3 cases). Changes in sSEP waveform was correlated to clinical symptoms (JOA score) and disability periods. In some cases, type 2 sSEP approached normal waveform after the operation, and there was an improvement in clinical symptoms. Evoked spinal cord action potentials were recorded during the operation in 15 cases (4 type 1 cases, 6 type 2 cases and 5 type 3 cases), and the location of the disc lesioned was inferred in all cases except in one case of type 1. In 3 type 1 cases, only one disc was lesioned. In all type 2 and type 3 cases, more than two discs were lesioned. It was therefore considered that when only one disc was lesioned, sSEP did not necessarily exhibit abnormalities. PMID- 2254392 TI - [Effects of lithium on mouse hematopoiesis]. AB - Both in vitro and in vivo effects of lithium on mouse hematopoiesis were investigated. The addition of 1 mmol lithium carbonate to the culture enhanced in vitro colony formation of the granulocyte macrophage precursor (CFU-GM) by 26%, the megakaryocyte precursor (CFU-Meg) by 29%, and the erythrocyte precursor (CFU E) by 46% as compared to the control culture without lithium carbonate. Lithium resulted in an increase of colony size for both the CFU-Meg and the CFU-E. Oral administration of lithium chloride at daily doses of 0.3 mg caused a significant increase in granulocytes 3 to 12 days after the start of administration. It also resulted in a mild elevation of the platelet count, but it had no influence on hematocrit. The number of the CFU-GM increased transiently on day 3 of the lithium administration and subsequently returned to the pretreatment level. Furthermore lithium accelerated the recovery of the granulocyte count and bone marrow CFU-GM content after 300 rad total body X ray irradiation. PMID- 2254393 TI - [Seroepidemiological study of rubella in Thailand]. AB - The epidemiology of rubella in Thailand was studied by measuring the HI antibodies in 2,798 human serum samples collected in 1977 and from 1982 through 1986. In the study of the Meo and Karen hill tribes and employees of the Raming Tea Plantation living in high land in 1977, high antibody-negative rates against rubella were observed among young children aged 14 or less, so that the antibody was assumed to have been acquired by most of the people aged 15 or over. However, the antibody level in those aged 15 or older differed from group to group. Employees of a tobacco factory and students at a high school in Sarapij were studied. Only two of the 54 employees had the negative antibody. The geometric mean antibody titers were as high as log2 7.081 and 7.058, respectively, which suggested an epidemic of rubella close to the time the specimens were collected. The antibody levels of patients with complaints other than rubella were compared between Chiang Mai and Bangkok in 1977. No significant difference was observed between the two cities in the 20 to 24 years age group but the antibody-negative rate was higher in Bangkok than in Chiang Mai. Serum samples collected from children in the Comprehensive Child Care Clinic, Chiang Mai University, in 1982, 1984 and 1985 were tested for their antibody levels to rubella. The age by which the subject children had naturally acquired the antibody was lower in 1982 than in 1985. The antibody-negative rate of outpatients in Chiang Mai University Hospital in 1985 was definitely higher than that in 1977, and that in 1977 was lower than that of adults in Chiang Mai in 1983 to 1986. These data would suggest that a severe epidemic of rubella prevailed in the Chiang Mai district before 1977, but the disease was not common during the eight subsequent years. Our data in Thailand were compared with records in Japan in 1976. In Japan the antibody negative rate decreased with age and it was lower than 5% in adults aged 30 years or more. Conversely, in Thailand the antibody-negative rate decreased by 20 to 24 years of age but it was still more than 25% after 25 years of age. The geometric mean antibody titre of the antibody-positive people decreased with age in Japan, but in Thailand it was as high as log2 6.33, even in adults of 30 or more years of age. PMID- 2254394 TI - [The arterial distribution to the abdominal digestive organs in human fetuses]. AB - The arterial supply of the abdominal digestive organs and the developmental process were studied in 25 Japanese fetuses from 3 months to 9 months old into whose arteries latex rubber was injected. The results were as follows: 1) The branching patterns of the celiac trunk were classified into 5 types. The most common type or the complete celiac trunk was found in 18 cases (72%). Four variation types or incomplete celiac trunks were found in 7 cases (28%). 2) The rates at which the following arteries were observed in the stomach were as follows: 100% for the left gastric artery, 100% for the left and right gastroepiploic artery, 100% for the short gastric artery, 100% for the gastroduodenal artery, 92% for the right gastric artery, 24% for the branch of the left inferior phrenic artery, and 16% for the posterior gastric artery arising from the splenic artery. The left gastric artery was better developed than the other arteries in 3-month-old fetuses. 3) The rates at which the following arteries were observed in the liver were as follows: 100% for the proper hepatic artery, 28% for the accessory left hepatic artery and 8% for the accessory right hepatic arteries. The accessory left hepatic artery in 3-month old fetuses was better developed than in older fetuses. 4) The rates at which the following arteries were observed in the pancreas were follows: 100% for the branches of the splenic artery, 100% for the branches of the gastroduodenal artery and 100% for the branches of the superior mesenteric artery. Further, dorsal pancreatic arteries not arising from the splenic artery were found in 20% of cases. The dorsal and great pancreatic arteries branching from the splenic artery could not be distinguished from one another in younger fetuses. 5) The rates at which the following arteries were observed in the duodenum were as follows: 100% for the branches of the superior and the inferior pancreaticoduodenal arteries. This arterial supply was the same in all the fetuses. 6) The arterial supply of the jejunum and the ileum were as follows: the jejunum and the ileum were supplied only by the branches of the superior mesenteric artery. The minimum number of the branches was 7 and the maximum 12. 7) The arterial supply of the large intestine was as follows: the caecum was supplied only by the ileocolic artery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254395 TI - [Morphological studies on the distribution of the anterior ethmoidal nerve in Japanese adults and fetuses]. AB - The anterior ethmoidal nerve (a.e.n.) was examined in 10 human adults (40-89 years old) and 5 fetuses (7 months). A.e.n. arises from the naso-ciliary++ nerve, which is the first division of the trigeminal nerve. From this point to the crista galli, a.e.ns. were observed under a dissection microscope in relation to their direction and distribution. The following results were obtained: 1) The number of a.e.n. i. The number of a.e.n. was 1 to 3 (1.45 on average) when they arose from the naso-ciliary nerve in the adults. ii. In the fetuses, the number of a.e.n. was 1 to 2 (1.1 on average). 2) The length of a.e.n. i. The length was 12.0 mm to 24.0 mm (17.3 mm on average) in the adults. ii. In the fetuses, the length was 2.0 mm to 7.0 mm (5.0 mm on average). 3) The anterior ethmoidal branch (e.b.). The anterior ethmoidal branch (e.b.) supplies the mucous membrane of the ethmoidal sinus. i. The number of e.bs. was 20 on the right side and 22 on the left in 8 adult cases. In the upper wall of the ethmoidal sinus, the number of e.bs. was 1.0 on average. In the medial wall of the ethmoidal sinus, the number of e.bs. was also 1.0 on average. In the lateral wall of the ethmoidal sinus, the number of e.bs. was 0.2 on average. ii. The number of e.bs. was 3 on the right side and 2 on the left in 3 fetus cases. In the upper wall of the ethmoidal sinus, the number of e.bs. was 0.2 on average. In the medial wall of the ethmoidal sinus, the number of e.bs. was 0.3 on average. No e.bs. were found in the lateral wall. 4) The anterior ethmoidal foramen. The anterior ethmoidal foramen was examined to determine its positional relation to the angle of the crista galli. i. The angle was 40.0 degrees to 10.0 degrees and 30.0 degrees on average in the adults. ii. In the fetuses, the angle was 50.0 degrees to 20.0 degrees and 43.2 degrees on average. PMID- 2254396 TI - [Stress analysis and movement in sacroiliac joints]. AB - Biomechanical experiments were performed on sacroiliac joints of the cadaver pelvis in three different positions to determine changes in stress pattern. The infrared stress analyzing method was used. In the neutral position, principal stress was observed in the middle to upper part of the sacrum, adjacent to the sacroiliac joints, in the central area of the ilium, and in the acetabular region. In the anterior tilting position, the stress on the sacroiliac joints was smaller than in the posterior tilting position, while it was greater in the symphysis pubis area. Further experiments with dial gauges were performed to measure load-displacement value in four cadaver pelves. Vertical loads of up to 100 kg were applied to the fourth lumbar vertebra. At the maximum test loads, displacement of the anterior surface of the first sacral vertebra ranged from 0.18 mm to 0.73 mm in the anterior direction. In conclusion, it is clear that the range of movement in the sacroiliac joints is very small and that this joint plays a significant role in the maintenance of stability in the pelvic girdle. PMID- 2254397 TI - Caroli's disease associated with liver cirrhosis. An autopsy case. AB - Caroli's disease is one of the rare congenital conditions associated with the cystic dilatation of intrahepatic bile ducts. This is a case report of a 41-year old Japanese male who complained of jaundice and general fatigue at the age of 34 for the first time. He was clinically diagnosed as having Caroli's disease by physical examination and image analyses study. The patient died after seven years and three months from the onset of the disease on account of renal function impairment. An autopsy was performed, revealing cystic dilatation of the intrahepatic bile duct, associated with a cirrhotic liver and also evidence of portal hypertension, substantiated by esophageal varices and splenomegaly. The liver weighed approximately 2,200 g. A histological investigation revealed typical morphological evidence of cirrhotic glomerulopathy and tubular degeneration with the presence of calcium casts in the dilated tubuli. The lung revealed diffuse alveolar damage with partial organization associated with remarkable polymorphonuclear and macrophagic infiltration. In this paper, the pathogenesis of the cirrhotic change, biliary duct abnormality and potential malignant transformation in the liver are discussed in relation to Caroli's disease. PMID- 2254398 TI - Functional significance of white blood cells in the male and female reproductive tract. AB - The functional significance of white blood cells in the modulation of an anti sperm antibody response, prevention of infection (including HIV) sperm transport/storage and sperm function is extensively discussed. A critical review of the existing literature is presented with future experimental lines of investigation outlined. A lack of controlled clinical studies in the human to validate data from animal species--for example--the involvement of white blood cells in the transport and storage of sperm in the female tract and the possible adverse effect of pathology (i.e. endometriosis) on these functions are presented. In conclusion, with the advent of modern techniques, e.g. monoclonal antibodies and sophisticated sperm function tests, many of the questions raised should be answered in the near future. PMID- 2254399 TI - CA-125 secretion by luteal phase endometrium in vitro. AB - The source of CA-125 in normal women and the mechanisms which control CA-125 production remain to be defined. This study was initiated to examine the pattern of secretion of CA-125 from luteal phase endometrium. Endometrial samples were obtained during the early luteal phase (histological days 16-18) and late luteal phase (histological days 25-27) from ovulatory women with a laparoscopically normal pelvis. The tissue was maintained in explant culture using Trowell's T-8 medium with either no additions (NA), progesterone (P), oestradiol (E2), or E2 + P. The concentration of CA-125 in spent media from the second day in culture was determined by immunoradiometric assay. In early luteal endometrium, the concentration of CA-125 in spent media from the NA treated wells was significantly higher than when the endometrium was exposed to either P or E2 + P. Similar differences were noted between treatments for the late luteal endometrium. Within each treatment, there was a higher concentration of CA-125 in the spent media from the late versus the early luteal endometrium. We conclude that the endometrium is a potential source of serum CA-125 and that endometrial CA-125 is suppressed by P in both the early and the late luteal phase. Further, there appears to be an increase in endometrial CA-125 secretion from the early to the late luteal phase. PMID- 2254400 TI - Detection of anti-sperm antibodies in serum, seminal plasma and cervical mucus by the immunobead test. AB - Anti-sperm antibodies in serum and seminal plasma were detected by means of an indirect immunobead test (IBT). Immunobeads with separate specificites for each immunoglobulin class (IBT-IgG, IBT-IgM, and IBT-IgA) were used. Semen parameters were controlled in all sperm donors and Biggers-Whitten-Whittingham (BWW) medium supplemented with human serum albumin (HSA) was used to increase sperm motility. This technique was tested with high titre anti-human sperm sera induced in rabbits. Sperm tails showed a good response by IBT. We included in this study 178 men and 35 women evaluated for infertility and the sera were also tested by the Tray Agglutination Test (TAT). Although the presence of semen markers such as agglutination or trembling of spermatozoa is meaningful even by itself, the percentage of anti-sperm antibodies was increased in the patients with markers, both using IBT (21.4%) and using TAT (35.7%). At high titres of specific immunoglobulins (rabbit antisera and vasectomized men), the correlation between IBT and TAT techniques was better than in sera with very low titres, in which more positive TAT's were detected. PMID- 2254401 TI - Antisperm antibodies induce polyspermy by promoting adherence of human sperm to zona-free hamster eggs. AB - Certain antisperm antibodies (ASAs) in the sera of infertile men or women promote the penetration of zona-free hamster eggs by spermatozoa. We have shown previously that this enhancement of penetration occurs through mechanisms other than an alteration in the acrosomal structure of antibody-labelled spermatozoa. In the present study, small limited populations of antibody-labelled and antibody free spermatozoa from fertile donors were observed serially by phase contrast, epifluorescence and scanning electron microscopy following their adherence to the oolemma of zona-free hamster eggs. The adherence of ASA-labelled spermatozoa to the zona-free hamster egg was markedly increased and occurred earlier when compared with antibody-free spermatozoa from the same ejaculate. The likelihood of entry of an antibody-labelled spermatozoon into the ooplasm, however, once adherent to the oolemma was not different to that of an antibody-free spermatozoa, and the ultrastructural steps of incorporation of antibody-labelled human spermatozoa were also similar to those observed during fertilization of hamster eggs by spermatozoa of several other species. These observations indicate that ASAs promote polyspermic fertilization of zona-free hamster eggs primarily through their enhancement of sperm--oolemmal binding. PMID- 2254402 TI - Severe ovarian hyperstimulation syndrome and cerebrovascular accidents. PMID- 2254403 TI - Abnormal chromosomal arrangements in human oocytes. AB - Ninety-one human oocytes, lacking signs of fertilization 50 h after insemination in vitro, were investigated cytogenetically to assess the frequency and type of chromosomal abnormalities. Chromosome spreading permitted adequate karyotyping in 55 oocytes. Non-determined numerical aberrations occurred with the following frequencies: hypohaploidy, 10.9% (6/55), hyperhaploidy, 14.5% (8/55) and hyperdiploidy, 3.6% (2/55). Total aneuploidy occurred with a frequency of 29.1% and was observed in oocytes from 30 patients. No correlation was found between specific chromosomal aberrations and type of infertility, stimulation treatment or gonadotrophin levels. On the other hand, the frequency of aneuploidy was significantly higher (P less than 0.05) in patients greater than 35 years of age. Two chromosomal complements (3.6%) had structural rearrangements; one oocyte had both structural and numerical chromosomal abnormalities and the other had differently condensed regions on the long arms of three chromosomes from group C. The overall frequency of chromosomal aberrations was 32.7%. Only two samples contained an additional set of polar body chromosomes. Thirteen oocytes presented sperm chromosomes in an arrested stage of premature chromosome condensation of the G1 phase and four oocytes showed asynchronous condensation of pronuclear chromosomes. Finally, it was concluded that the high proportion of chromosomal aberrations observed in human oocytes may contribute significantly to abnormal embryonic development in vitro. PMID- 2254404 TI - Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. AB - Normally fertilized human embryos biopsied 3 days after in-vitro fertilization (IVF) have been examined for effects on viability and development in vitro after removal of one or two cells at the 8-cell stage (1/8 and 2/8) from each embryo. A high proportion of 7/8 and 6/8 biopsied and unmanipulated embryos developed to the blastocyst stage between days 5 and 6 (79, 71 and 59%, respectively), and many biopsied embryos (56%) hatched from the zona pellucida in vitro. The viability of biopsied embryos which developed to the blastocyst stage was assessed by daily non-invasive measurement of the uptake of two energy substrates, glucose and pyruvate. Uptake of both substrates was generally lower in 7/8 and 6/8 biopsied embryos but only in proportion to the reduced cellular mass. The total cell number and the numbers of both trophectoderm (TE) and inner cell mass (ICM) cells in biopsied embryos at the blastocyst stage, counted by differential labelling of their nuclei, were also reduced in proportion but the ratio of ICM to TE cells was maintained in both 7/8 and 6/8 biopsied embryos. We conclude that removal of one or two cells at the 8-cell stage, while reducing the cellular mass, does not adversely affect the preimplantation/development of biopsied embryos in vitro and suggest that this approach could be used for preimplantation diagnosis of genetic defects. PMID- 2254405 TI - The hypoosmotic swelling test and cryosurvival of human spermatozoa. AB - The hypoosmotic swelling test is a simple laboratory test to evaluate the functional integrity of the membrane of human spermatozoa. This test was performed on 83 samples of human semen before cryopreservation to determine whether it has any predictive value for the cryosurvival of human spermatozoa. Stepwise regression analysis demonstrated that conventional sperm characteristics, including the concentration, motility, normal morphology and viability, of pre-freeze semen samples were of limited value in predicting the cryosurvival of human spermatozoa. Further, the hypoosmotic swelling test results from pre-freeze semen samples did not correlate with the post-thaw motility or the survival rate of spermatozoa after cryopreservation. PMID- 2254406 TI - Computerized semen analysis with sperm tail detection. AB - We evaluated a recently developed computerized semen analyser that detects spermatozoa not only by the criteria of size, contrast and movement but also by the morphological characteristics of the sperm tail. Comparison of the sperm concentration in 33 semen samples measured by conventional and by computerized semen analysis, as well as by flow cytometry, showed acceptable agreement between all three methods, although the mean differences and standard deviations were less for conventional than for computerized analysis when compared to flow cytometry as a reference method. Motility estimates were lower by the computer system for values between 1 and 40%. Higher motilities showed no systematic error. In conclusion, the improved algorithms for sperm detection yield more reliable data for sperm concentration and motility than previous systems of computerized semen analysis. PMID- 2254407 TI - A comparison of the freezing of human semen in the uncirculated vapour above liquid nitrogen and in a commercial semi-programmable freezer. AB - The cooling rates inside 0.25-ml semen straws filled with glycerol, egg yolk, citrate buffer were compared between a standard vapour freezing procedure and freezing in a Nicool LM-10 semi-programmable freezer. During vapour freezing, the cooling rate at the bottom of the straw was much faster than at the top and there was considerable variation between replicates. By contrast, position within the straw did not affect the cooling rate in the Nicool LM-10 procedure and replicates were more consistent. More motile spermatozoa survived the Nicool freezing procedure and their lateral head displacement was greater than vapour frozen spermatozoa. However the percentage of intact spermatozoa and their velocity was very similar after the two procedures. We conclude that the freezing procedure using the Nicool LM-10 provides a comparatively economical way to achieve consistent semen freezing for research studies. PMID- 2254408 TI - A protein marker of hamster oocyte fertilization. AB - Using a polyclonal rabbit antiserum directed against guinea-pig heparin-binding placental protein (HBPP), we have demonstrated by indirect immunofluorescence the expression of this antigen by hamster preimplantation embryos. HBPP was localized to blastomeres, but not to the zona pellucida, of hamster preimplantation embryos conceived in vivo. Hamster embryos, from the pronuclear to hatched blastocyst stages, were HBPP-positive with greatest immunofluorescence detected at the pronuclear to 2-cell stages. Thereafter, HBPP-dependent fluorescence diminished. By contrast, mature spermatozoa and unfertilized metaphase II oocytes were HBPP negative. Direct microinjection of spermatozoa or diluent through the zona pellucida and into the ooplasm activated the oocytes to express HBPP. These findings demonstrate that expression of HBPP is a post-conceptional event limited to fertilized (or activated) oocytes and that transcription of paternal genomes was not required for HBPP expression. The distribution and temporal kinetics suggest that HBPP may be secreted or released by activated cortical granules into the perivitelline space and concentrated at the oolemma. Whereas hamster embryos conceived in vivo consistently demonstrated a uniformly distributed immunofluorescence, non-viable and degenerate embryos showed weak and patchy reactions. Thus, we have identified a heparin-interacting protein which may serve as a marker of in-vivo and in-vitro oocyte activation and embryo quality. PMID- 2254409 TI - Co-culture of 1-cell mouse embryos on different cell supports. AB - The development of 1-cell mouse embryos in explanted oviducts, on mouse and bovine oviduct epithelial cells and on two established cell line supports is compared. The best rates of blastocyst formation were obtained using explanted oviducts; mouse and to a lesser extent, bovine oviduct epithelial cells allow good embryonic development, associated with high viability after transfer of the blastocysts obtained in co-culture. MDBK (from bovine kidney) and Vero (from Green monkey kidney) have been tested. MDBK allows high rates of blastocyst formation (67%) and the blastocysts obtained are viable. Vero does not allow the 2-cell block to be overcome. Maintenance of cell polarity for all the feeder layers did not improve embryo development. A preliminary study on the metabolic modifications induced by the feeder layers showed no modifications at all related to a decrease in glucose, an increase in lactate and early embryonic development. On the other hand, for the free amino acids, cellular supports with high embryotrophic activity seem to mimic tubal secretions, especially with a high level of glycine. Neither a genital tract origin, nor a hormonal contribution are strictly necessary for embryo co-culture, as already demonstrated by co-culture with trophoblastic tissue. Established cell lines, which are easy to handle and control, could be useful tools in embryo biotechnology. PMID- 2254410 TI - Influence of blood clots in the cumulus complex on oocyte fertilization and cleavage. AB - Since multiple ovarian punctures are performed during oocyte retrieval, the likelihood of blood contaminating the follicular fluid is high. The purpose of this study was to determine whether the presence of blood clots, which are frequently seen in the cumulus of oocytes retrieved under ultrasound guidance, has any effect on fertilization and subsequent embryo cleavage and to identify oocyte characteristics which may predict these events. Oocytes were morphologically graded and the presence of blood clots in the cumulus was recorded. Cases in which the male partner had a total motile sperm count less than 20 x 10(6) on the day of insemination were excluded from the logistic regression analysis. The presence of blood clots in the cumulus was a negative predictor of cleavage [odds ratio (OR) = 0.54]. The results indicate that an oocyte with optimal quality is one which is spherical (OR = 5.45), has an expanded corona (OR = 3.80) and has no blood clots in the cumulus complex. PMID- 2254411 TI - Diagnosis and treatment of ectopic pregnancy by retrograde selective salpingography and intraluminal methotrexate injection: work in progress. AB - Selective retrograde trans-cervical salpingography was carried out in four patients in whom ectopic pregnancy was suspected. The Fallopian tube was catheterized using a catheter set designed in our centre. The 6F catheter was placed in the cornua and an inner coaxial catheter was easily introduced into the proximal portion of the Fallopian tube, guided by tactile impression. Contrast medium was then injected and a round haloed mass was seen. Thereafter, the Fallopian tube was catheterized using a metallic guidewire until its tip was adjacent to the ectopic pregnancy. The coaxial catheter was then advanced along the guidewire and after removal of the latter, 5-35 mg of methotrexate was injected into the Fallopian tube. This new procedure was simple, well tolerated and had no side effects. A tubal pregnancy was demonstrated and surgery was avoided in all cases. PMID- 2254412 TI - Ovarian pregnancy following in-vitro fertilization and embryo transfer. PMID- 2254413 TI - High-level production of Escherichia coli STb heat-stable enterotoxin and quantification by a direct enzyme-linked immunosorbent assay. AB - A convenient and sensitive enzyme-linked immunosorbent assay (ELISA) for the STb heat-stable enterotoxin of Escherichia coli was developed and used to quantify STb production by strains with a high level of expression. Based on an antigenic profile of the secreted form of STb, a synthetic peptide (STb3-27) spanning the major predicted epitope was synthesized, coupled to keyhole limpet hemocyanin, and used to immunize rabbits. Anti-STb3-27 antibodies were affinity purified on a synthetic peptide-Sepharose 4B column and used in a direct-binding STb ELISA. Based on a highly purified form of toxin as a standard, the ELISA detected as little as 1 to 2 ng of STb from crude culture filtrates. ELISA data revealed that natural STb-producing strains elaborate little STb in defined-medium cultures relative to that elaborated by a recombinant strain harboring a cloned copy of the estB gene. Replacement of the endogenous STb promoter with any of several highly active promoters, including a bacteriophage T7 promoter, a beta galactosidase promoter, and a tryptophan-beta-galactosidase hybrid (tac) promoter, increased the yield of STb 10- to 20-fold over levels obtained by an E. coli strain harboring the recombinant estB gene. The high level of STb antigen detected by the ELISA correlated with intestinal secretory activity. The combination of a convenient assay and effective hyperproduction of STb will serve as a basis for a large-scale toxin purification strategy. PMID- 2254414 TI - Irrigation-aspiration for culturing draining decubitus ulcers: correlation of bacteriological findings with a clinical inflammatory scoring index. AB - Biopsy of infected decubitus ulcers for culture disrupts tissues and may disseminate infection. Antimicrobial prophylaxis to prevent dissemination of infection may adversely affect biopsy culture results. Irrigation-aspiration to obtain submarginal specimens from draining decubitus ulcers was studied as an atraumatic, noninvasive culturing technique to serve as an alternative to biopsy in research activities. Two aspirates were obtained serially from 32 subjects; in 12 subjects, biopsies were also performed immediately. A median of 4.5 bacterial species was recovered per ulcer by irrigation-aspiration. Recent antimicrobial treatment had no evident effect on the recovery of bacterial species in general or, specifically, on the recovery of Bacteroides species. Concordance of results for both aspirates was 97.6% for aerobes and 91.8% for anaerobes, indicating no interactive methodological effect of the first irrigation-aspiration on the second. Compared with biopsy isolates for one aspirate, the sensitivity was 93% and the specificity was 99.0%; for another aspirate, the sensitivity was 94.7% and the specificity was 99.5%. The positive predictive value for either aspirate was greater than or equal to 93.9%. A weighted clinical index to score inflammatory ulcer characteristics was devised (score range, 0 to 15). In the absence of anaerobes in 15 subjects, the mean score was 6.1 +/- 3.5; in the presence of anaerobes in 17 subjects, the mean score was 9.4 +/- 3.2 (P = 0.008). The presence of aerobic gram-positive or gram-negative species did not significantly affect scores. Irrigation-aspiration for culture and clinical scoring of inflammation should permit independent serial measures of bacteriological and clinical courses of draining decubitus ulcers without patient risk or discomfort. PMID- 2254415 TI - Evaluation of direct immunofluorescence, enzyme immunoassay, centrifugation culture, and conventional culture for the detection of respiratory syncytial virus. AB - Four methods of detecting respiratory syncytial virus (RSV) from clinical specimens were evaluated. A total of 410 specimens consisting of nasopharyngeal washes, aspirates, and swabs were simultaneously tested for the presence of RSV by direct immunofluorescence assay (DFA), enzyme immunoassay (EIA) (Kallestad Pathfinder), shell vial centrifugation culture (SVC), and conventional culture. DFA identified 146 (83%) of the 175 positive cases, EIA detected 153 (87%), SVC detected 127 (73%), and conventional culture detected 70 (40%). Conventional culture isolated an additional 19 respiratory viruses other than RSV. DFA and EIA were able to detect nonviable virus not isolated by a culture method, and SVC isolated low-titer virus not detected by conventional culture. DFA and EIA gave similar results; however, the EIA system was less dependent on technical expertise. The use of SVC enhanced the conventional culture system with 63 RSV isolates not recovered from the tube culture. We recommend complementary use of both culture and nonculture methods in the detection of RSV. PMID- 2254416 TI - Detection of pYV+ Yersinia enterocolitica isolates by P1 slide agglutination. AB - Rabbit polyclonal antisera were raised against the pYV-encoded outer membrane protein P1 of five Yersinia enterocolitica strains belonging to serogroups O:3, O:5,27, O:8, and O:9. Analysis of these strains with the sera showed that P1 presented at least six different antigenic factors. Two of the serum specimens were chosen to test the P1 agglutinability of 797 strains isolated from various sources. This technique appeared to be more reliable than autoagglutination and Ca2+ dependency to monitor the presence of the pYV plasmid. Hence, we propose this P1-mediated agglutination as a new and easy virulence test. PMID- 2254417 TI - Association of production of cell-detaching factor with the clinical presentation of Trichomonas vaginalis. AB - Recent work has shown that Trichomonas vaginalis produces a cell-detaching factor (CDF) that causes detachment of monolayer cells in vitro. To study the role of CDF as a pathogenic marker of disease, we studied the production of CDF in 12 clinical isolates of T. vaginalis. These isolates were also utilized in the mouse subcutaneous assay of Honigberg, which is the standard for pathogenicity of T. vaginalis. The isolates were divided into three groups based on clinical presentation (asymptomatic [n = 4], moderate [n = 4], and severe symptoms [n = 4]). CDF was assessed by harvesting the supernatant from the growth of T. vaginalis in cell culture and filtering the supernatant through a 0.45-microns pore-size filter. The filtrate was applied in a microtiter cytotoxicity assay. The mouse subcutaneous assay did not significantly differentiate among the isolates. However, CDF was strongly associated with clinical presentation by two way, repeated-measure analysis of variance (P = 0.025). Thus, CDF appears to correlate with clinical presentation and may be an important virulence marker in T. vaginalis pathogenesis. PMID- 2254418 TI - Hemolysins and other characteristics that help differentiate and biotype Staphylococcus lugdunensis and Staphylococcus schleiferi. AB - Reference strains and clinical isolates representing the newly defined species Staphylococcus lugdunensis and Staphylococcus schleiferi were examined with the battery of tests previously recommended (G.A. Hebert, C.G. Crowder, G.A. Hancock, W.R. Jarvis, and C. Thornsberry, J. Clin. Microbiol. 26:1939-1949, 1988) for other species of coagulase-negative staphylococci (CNS). The Staph-Ident system (Analytab Products, Plainview, N.Y.) supplemented with tests for synergistic hemolysis, adherence to glass, pyroglutamyl-beta-naphthylamide hydrolysis, and susceptibility to a set of five antimicrobial disks differentiated each of these species from other species of CNS and separated strains within each species into several biotypes. Most strains (95%) of S. lugdunensis produced a delta hemolysin like that seen with nine other species of CNS. Most strains (91%) of S. schleiferi produced a beta hemolysin, which is a unique characteristic among CNS. Most (95%) of the S. schleiferi but very few (12%) of the S. lugdunensis were adherence positive. Both hemolysins and adherins are potential virulence factors among CNS. Some (29%) of the S. lugdunensis were beta-lactamase positive. The S. lugdunensis were resistant to polymyxin B and bacitracin (10 U), but the S. schleiferi were susceptible to both disks. Clinical isolates of S. lugdunensis were aligned in 18 biotypes because of eight biochemical profiles and eight physiologic subtypes; isolates of S. schleiferi were in 8 biotypes because of three biochemical profiles and subtypes. These tools for correctly identifying and then biotyping two more clinical species of CNS should enhance both epidemiologic and ecologic investigations. PMID- 2254419 TI - Adherence measured by microtiter assay as a virulence marker for Staphylococcus epidermidis infections. AB - Staphylococcus epidermidis strains isolated from clinical sources showed a wide range of abilities to adhere to glass and plastic materials. The degree of adherence depended on a number of factors, most notably, the composition of the growth medium. Adherence was enhanced by the addition of glucose or oleic acid to the growth medium and inhibited by serum. We have demonstrated a statistically significant association between the quantitative assessment of adherence to polystyrene tissue culture plates and clinical relevance. No such association was found when adherence was assessed by the qualitative adherence assay. Possible new approaches for assessing the clinical relevance of coagulase-negative staphylococcal isolates are discussed. PMID- 2254420 TI - Mice and moles inhabiting mountainous areas of Shimane Peninsula as sources of infection with Yersinia pseudotuberculosis. AB - A total of 1,835 Yersinia spp. were isolated from 925 (60.5%) of 1,530 wild mice and from 139 (79.9%) of 174 moles living in mountainous areas of eastern Shimane Prefecture, Japan. The Yersinia spp. included 1,106 Yersinia enterocolitica, 26 Y. enterocolitica-like, 176 Yersinia mollaretii, 149 Yersinia frederiksenii, 70 Yersinia intermedia, 231 Yersinia kristensenii, 5 Yersinia aldovae, and 72 Yersinia pseudotuberculosis. Human pathogenic Y. enterocolitica was not isolated. Y. pseudotuberculosis was divided into 10 virulent 40- to 50-MDa plasmid-positive (P+) strains (serotypes 1b, 4b, and untypeable) and 62 plasmid-negative (P-) strains (serotypes 1b, 2b, 2c, 4a, 5a, 5b, 6, 7, and untypeable). P+ strains of serotypes 1b (two strains), 4b (seven strains), and untypeable (one strain) were isolated from nine Apodemus specious and one Apodemus argenteus. The isolates of Yersinia spp. were more frequently detected in newborn mice and during the breeding season. The P+ Y. pseudotuberculosis strains were recovered at less than 10(4) cells per g of the cecal contents. Thus, the prevalence of Yersinia spp. in small wild animals depends on the newborn animals born during the cold months, and wild mice in mountainous areas are important reservoirs of Y. pseudotuberculosis. PMID- 2254421 TI - Enumeration of mutans streptococci in clinical samples by using monoclonal antibodies. AB - Mutans streptococci have been strongly associated with dental caries. Two members of this group of bacteria, Streptococcus mutans and Streptococcus sobrinus, are often found in human dental plaque. Identification of mutans streptococci on the basis of sugar fermentation is troublesome and easily leads to erroneous conclusions. Furthermore, the recovery on selective media differs for different species. This causes incorrect enumeration of S. mutans and S. sobrinus in clinical samples. The aim of this study was to develop a method for simultaneous identification and enumeration of S. mutans and S. sobrinus in dental plaque and saliva samples. With this immunoblot technique (IBT), significantly more plaque samples containing S. sobrinus were detected than on the selective medium Trypticase-yeast-cysteine-sucrose-bacitracin agar (TYCSB) (P less than 0.01). The numbers of plaque samples harboring S. mutans were equal on TYCSB and by IBT. However, the numbers of CFU of S.mutans as well as of S. sobrinus detected with the IBT were significantly higher than those obtained on TYCSB (P less than 0.001). The recovery of primary isolations of S. sobrinus on TYCSB seems to have been inhibited in 26 of the 45 S. sobrinus-containing plaque samples. False positive or false-negative reactions with the IBT were not found. PMID- 2254422 TI - Use of sequential enzyme immunoassay and direct fluorescent antibody tests for detection of Chlamydia trachomatis infections in women. AB - Endocervical infections due to Chlamydia trachomatis remain difficult to diagnose due to the lack of an inexpensive, rapid, and accurate test. We evaluated an alternative strategy for diagnosis in which initial screening was performed with an enzyme immunoassay (Chlamydiazyme) followed by a direct fluorescent antibody (DFA) test on specimens in which the Chlamydiazyme optical density (OD) reading fell in an intermediate zone. Lowering the Chlamydiazme OD ratio (specimen to control) used to define a positive test from 1.0 (the ratio suggested by the manufacturer) to 0.3 raised the sensitivity of Chlamydiazyme from 73 to 83%. Confirmation of those specimens having OD ratios of 0.3 to 0.99 by DFA testing increased the specificity of Chlamydiazyme from 95 to 100%. This strategy necessitated performance of the DFA test on 5% of the specimens. Lowering the cutoff OD ratio below 0.3 increased the sensitivity even further but required DFA testing on greater than 25% of the specimens. Use of an adjusted positive cutoff value for defining positive enzyme immunoassays followed by DFA confirmation for intermediate-zone readings may be a feasible approach for some laboratories that lack cell culture facilities. PMID- 2254423 TI - Detection of the aerolysin gene in Aeromonas hydrophila by the polymerase chain reaction. AB - Synthetic oligonucleotide primers were used in a polymerase chain reaction (PCR) technique to detect the gene for aerolysin in strains of Aeromonas hydrophila and to screen for identical genes in A. caviae, A. sobria, and A. veronii isolated from patients with diarrheal disease. Primers targeted a 209-bp fragment of the aer gene coding for the beta-hemolysin and detected template DNA only in the PCR using nucleic acid (NA) from hemolytic strains of A. hydrophila which were also cytotoxic to Vero and CHO cells and enterotoxic in suckling-mouse assays. PCR amplification of NA from hemolytic A. sobria or nonhemolytic A. hydrophila and A. caviae strains was consistently negative. Primer specificity was determined in the PCR by using NA extracted from 56 strains of bacteria, including hemolytic Escherichia coli and Listeria monocytogenes as well as several recognized enteric pathogens defined in terms of their toxigenicity. The detection limit for the aerolysin gene by PCR amplification was 1 ng of total NA. The PCR clearly identified aerolysin-producing strains of A. hydrophila and may have application as a species-specific virulence test because other hemolytic Aeromonas species tested were negative. PMID- 2254424 TI - Isolation of 16 strains of Coxiella burnetii from patients by using a sensitive centrifugation cell culture system and establishment of the strains in HEL cells. AB - Q fever, caused by Coxiella burnetii, may be acute or chronic. Only a few strains of C. burnetii have been isolated due to the difficulty and hazard of isolation. We report here the isolation using a centrifugation shell vial technique of 16 new strains from patients suffering chronic Q fever. Twenty-four samples were inoculated onto human embryonic lung (HEL) fibroblast cell monolayers growing in shell vials. C. burnetii was detected 6 days later by using immunofluorescence. Samples from valves (n = 10), arterial prostheses (n = 2), bone (n = 3), skin biopsy (n = 1), bone marrow (n = 1), and blood (n = 5) from 16 patients were successfully cultured. Two cerebrospinal fluid samples from two patients were negative. The strains were subcultured in HEL cells and are now established. The technique is sensitive and less hazardous than animal inoculation. We recommend the shell vial technique for isolation of C. burnetii. PMID- 2254425 TI - Practical and economical method for using biotinylated DNA probes with bacterial colony blots to identify diarrhea-causing Escherichia coli. AB - A simple and economical method was developed for using biotinylated DNA probes to hybridize with bacterial colonies belonging to the various categories of diarrhea causing Escherichia coli. Simplification and cost containment were achieved by using Whatman no. 541 filter papers instead of nitrocellulose, by minimizing the concentration of proteinase K (an expensive but necessary reagent used to pretreat the colony blots prior to hybridization with biotin-labeled DNA probes) and by reusing hybridization solution containing labeled probe DNA. After exposing the colony blots to lysing solution and steam, followed by lysozyme (1.5 mg/ml), sucrose (25%), and proteinase K (10 micrograms/ml) treatments, biotinylated probes were used to detect enterotoxigenic, enteropathogenic, enterohemorrhagic, diffuse adherence, and enteroinvasive categories of diarrhea causing E. coli with a high level of sensitivity and specificity. Three independent observers who were experienced in reading DNA blots recorded remarkably similar results, while less satisfactory results were obtained when the blots were read by an inexperienced observer. This technique will be useful in laboratories in which radioactive isotopes are unavailable or impractical and in which budgets are restricted. PMID- 2254426 TI - Enzyme-linked immunoassay for detection of Cryptosporidium antigens in fecal specimens. AB - Cryptosporidium sp. is a ubiquitous 4- to 6-micron protozoan parasite infecting the intestinal tract of humans. It causes mild to fulminant diarrhea in patients, especially immunocompromised persons, and it may be hard to detect by microscopic fecal examination. An indirect, double-antibody enzyme-linked immunosorbent assay (ELISA) was developed using specifically produced goat and rabbit antisera to detect Cryptosporidium antigens in human feces. Of 62 frozen stools from patients with cryptosporidiosis, as detected by at least two microscopic diagnostic techniques, 51 were positive by ELISA; all ELISA-negative specimens came from patients with fewer than five oocysts per 0.01 ml of concentrated fecal sample examined after modified acid-fast or fluorescent monoclonal antibody staining. A total of 182 specimens from persons without Cryptosporidium infection were negative by ELISA in 176 instances; 3 ELISA-positive specimens came from patients with cryptosporidiosis diagnosed earlier. The sensitivity of the assay was 82.3%, and specificity was 96.7%. The predictive value of a positive ELISA was 89.5%, and the predictive value of a negative ELISA was 94.2%. The ELISA was not affected by the presence of eight other intestinal parasites but was sometimes affected by repeated freezing and thawing of fecal specimens. All fecal specimens were heated to 100 degrees C for 2 min to reduce proteolytic enzyme activity, although the necessity of this step needs further evaluation. This first generation ELISA is a simple, rapid, easily standardized test for Cryptosporidium antigens in stool samples which will be useful for diagnosis and for large-scale epidemiologic studies. PMID- 2254427 TI - Importance of salmonellae and Campylobacter jejuni in the etiology of diarrheal disease among children less than 5 years of age in a community in Bangkok, Thailand. AB - The etiology of diarrhea in children less than 5 years of age in a low-income housing project in Bangkok, Thailand, was determined over 1 year. Nontyphoidal salmonellae (13%), Campylobacter jejuni (12%), rotavirus (12%), enterotoxigenic Escherichia coli (7%), shigellae (6%), E. coli that hybridized with the enteropathogenic E. coli adherence factor probe (3%), and enteroinvasive E. coli (1%) were identified in 345 episodes of diarrhea in children less than 5 years of age. Salmonellae were identified in 17% and C. jejuni was identified in 15% of 54 children less than 6 months of age with diarrhea. Shigellae, enteroinvasive E. coli, enteropathogenic E. coli adherence factor, and enterotoxigenic E. coli were not isolated from children less than 6 months of age. Since salmonellae and C. jejuni were the most common bacterial pathogens identified in children less than 6 months of age, efforts to prevent transmission of salmonellae and campylobacter to young children should be a public health priority in Bangkok. PMID- 2254428 TI - Enhanced radiometric detection of Mycobacterium paratuberculosis by using filter concentrated bovine fecal specimens. AB - A commercial radiometric medium, BACTEC 12B, was modified by addition of mycobactin, egg yolk suspension, and antibiotics (vancomycin, amphotericin B, and nalidixic acid). Decontaminated bovine fecal specimens were filter concentrated by using 3-microns-pore-size, 13-mm-diameter polycarbonate filters, and the entire filter was placed into the radiometric broth. Comparison of the radiometric technique with conventional methods on 603 cattle from 9 Mycobacterium paratuberculosis-infected herds found that of 75 positive specimens, the radiometric technique detected 92% while conventional methods detected 60% (P less than 0.0005). Only 3.9% of radiometric cultures were contaminated. To measure the effect of filter concentration of specimens on the detection rate, 5 cattle with minimal and 5 with moderate ileum histopathology were sampled weekly for 3 weeks. M. paratuberculosis was detected in 33.3% of nonfiltered specimens and 76.7% of filtered specimens (P less than 0.005). Detection rates were directly correlated with the severity of disease, and the advantage of specimen concentration was greatest on fecal specimens from cattle with low-grade infections. Detection times were also correlated with infection severity: 13.4 +/- 5.9 days with smear-positive specimens, 27.9 +/- 8.7 days with feces from cows with typical subclinical infections, and 38.7 +/- 3.8 days with fecal specimens from cows with low-grade infections. Use of a cocktail of vancomycin, amphotericin B, and nalidixic acid for selective suppression of nonmycobacterial contaminants was better than the commercial product PANTA (Becton Dickinson Microbiologic Systems, Towson, Md.) only when specimens contained very low numbers of M. paratuberculosis. Radiometric culture of filter concentrated specimens generally doubled the number of positive fecal specimens detected over conventional methods, making it a useful tool for diagnosis and control of bovine paratuberculosis. PMID- 2254429 TI - Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients. AB - To determine the incidence rate of complications associated with vascular catheters in intensive care unit patients and to analyze risk factors for a positive vascular culture, we performed a multicenter study of intensive care unit patients at eight French hospitals. During the study period, 865 intravenous catheters were inserted in 566 patients; 362 (41.8%) were peripheral catheters, and 503 (58.2%) were central catheters. Local complications (i.e., infiltration) occurred significantly more often with peripheral than with central catheters (P less than 0.001); in contrast, fever and bacteremia were significantly more often associated with central than with peripheral catheters (P less than 0.01 and P less than 0.05, respectively). The culture of the vascular-catheter tip was positive for 24% of central catheters (32 of 1,000 catheters days) and for 9% of peripheral catheters (21 of 1,000 catheters days). Staphylococcus epidermidis was the most common microorganism isolated from both peripheral and central catheters, followed by Staphylococcus aureus and Pseudomonas aeruginosa. No significant risk factor associated with positive cultures for peripheral catheters was found by univariate analysis. In contrast, the purpose of the cannula (nutrition and monitoring of central venous pressure), the insertion site (jugular), the dressing type (semipermeable transparent dressing), the antiseptic used to prepare the insertion site (povidone iodine), and routine changing of the intravenous administration set were significantly associated with positive cultures of central catheters. Three factors, duration of catheterization, use of a semipermeable transparent dressing, and the jugular insertion site, were found to be independently associated with positive cultures of central catheters by multivariate analysis. PMID- 2254430 TI - Assessment of a new hub design and the semiquantitative catheter culture method using an in vivo experimental model of catheter sepsis. AB - An in vivo model of hub-related catheter sepsis in rabbits is reported. The model was used to investigate the protection offered by a new hub design against external contamination by Pseudomonas aeruginosa or Staphylococcus epidermidis and to reassess the diagnostic value of the semiquantitative culture method in bacteremia of endoluminal origin. Contamination of conventional Luer-Lock connectors was followed by clinical sepsis, positive catheter segment cultures, or both, whereas contamination of the new hub was followed by complete protection. Clinical and bacteriological discrepancies observed between contamination with P. aeruginosa and S. epidermidis suggest that the virulence of microorganisms may account for differences in the natural history of hub originated catheter sepsis. The semiquantitative extraluminal method for catheter culture yielded less than 15 CFU in three animals with proven bacteremia and should not be used as the "gold standard" to define catheter-related bacteremia. PMID- 2254431 TI - Comparison of Guizotia abyssinica seed extract (birdseed) agar with conventional media for selective identification of Cryptococcus neoformans in patients with acquired immunodeficiency syndrome. AB - Growth of Cryptococcus neoformans from the sputum of patients with acquired immunodeficiency syndrome may be obscured by oral contamination with Candida albicans on conventional media. We prospectively compared direct plating of sputum and urine onto birdseed agar and compared birdseed agar plating with plating onto Mycosel and Sabouraud dextrose agar cultures. Thirty-two sputum and three urine specimens were compared. C. neoformans was isolated from five specimens. In two specimens, one of sputum and one of urine, C. neoformans was detected only on the birdseed agar plate because of overgrowth on the conventional media by C. albicans. C. neoformans produced dark colonies on birdseed agar, unlike C. albicans, which produces white colonies. The use of birdseed agar as the primary culture medium for sputum and urine specimens from patients with acquired immunodeficiency syndrome increases sensitivity for C. neoformans. PMID- 2254432 TI - Effect of BiTek agar on lysostaphin susceptibility of staphylococci. AB - Staphylococci which were considered to be lysostaphin susceptible on P agar containing Bacto-Agar showed different degrees of resistance to lysostaphin when tested on P agar made with BiTek agar. As a result, lysostaphin-susceptible strains were misidentified as lysostaphin-resistant strains. PMID- 2254433 TI - Osteomyelitis and synovitis produced by Mycobacterium marinum in a fisherman. AB - We report a case of osteomyelitis and synovitis produced by Mycobacterium marinum in the left index finger of a fisherman. A combination of surgical intervention and antimicrobial therapy with minocycline, rifampin, and ethambutol was efficacious. PMID- 2254434 TI - Modified Feist broth as a serum-free alternative for enhanced production of protective antigen of Erysipelothrix rhusiopathiae. AB - The production of protective antigen in modified serum-free nutrient broth (H. Feist, K.-D. Flossmann, and W. Erler, Arch. Exp. Veterinaermed. 30:49-57, 1976) and in brain heart infusion broth supplemented with 10% horse serum (BHIS) was evaluated for six strains of Erysipelothrix rhusiopathiae serotypes 1a, 2, 2b, 4, and N. All six strains grew to higher cell densities in modified Feist medium than in BHIS and produced larger amounts of 64,000- to 66,000- and 39,000- to 40,000-molecular-weight antigens involved in immunity to erysipelas. A vaccine produced in Feist medium from E. rhusiopathiae SE-9 (serotype 2) was highly effective in a mouse protection test. We therefore suggest that modified Feist medium is an excellent, if not superior, alternative to BHIS for production of erysipelas vaccine. PMID- 2254435 TI - Ability to bind salivary alpha-amylase discriminates certain viridans group streptococcal species. AB - A collection of 144 viridans group streptococcal strains recently characterized as part of a taxonomic study was examined for the ability to bind salivary alpha amylase. This property was found in most strains of Streptococcus gordonii and Streptococcus mitis and in occasional strains of Streptococcus anginosus and Streptococcus salivarius. In contrast, all strains of Streptococcus sanguis, Streptococcus oralis, Streptococcus vestibularis, and Streptococcus mutans lacked alpha-amylase-binding capacity. A rapid and easy assay described in this paper may be an important supplementary test for identification of oral streptococci. PMID- 2254436 TI - Differential production of slime under aerobic and anaerobic conditions. AB - A series of 37 clinical isolates of coagulase-negative staphylococci previously identified as negative for slime production by the tube test were reexamined by the tissue culture plate test under aerobic and anaerobic conditions. None of the strains produced slime under anaerobic conditions; however, five strains (13%) produced slime under aerobic conditions. PMID- 2254437 TI - Reproducibility of API Staph-Ident system identifications of coagulase-negative staphylococci isolated from blood. AB - Fifty-five isolates of coagulase-negative staphylococci from blood were identified four times each by using the API Staph-Ident (API-SI) system to determine the identification reproducibility of the system. Identifications were determined by using both Version 1 and Version 2 of the API-SI Profile Index. The 75 to 100% reproducibility levels, including reproducible nonidentifications, were 98.2% for Version 1 and 96.4% for Version 2. Version 1 gave an identification for 92.5% of the isolates with a 75 to 100% reproducibility, while Version 2 gave an identification for 100% of the isolates with a 75 to 100% reproducibility. The reproducibility of the API-SI identifications of coagulase negative staphylococci from blood was good. PMID- 2254438 TI - Histochemical and physiological properties of Rana temporaria tibialis anterior and lumbricalis IV muscle fibres. AB - Histochemical analysis was used to study the relationship between Rana temporaria tibialis anterior and lumbricalis IV fibre cross-sectional areas and concentrations of myosin ATPase and NADH reductase. Both tonic and twitch fibre types were histochemically identified in each muscle and the twitch fibres were subgrouped into types 1, 2, and 3. Fibres that had the largest cross-sectional areas were identified as the fibres which contained the highest myosin ATPase activity and the lowest NADH reductase activity (type 1 fibres). However, this relationship was more pronounced in the tibialis anterior muscle. In addition, single fibres from both muscles were isolated and injected with Ca2+ indicator aequorin. The fibres isolated from the tibialis anterior muscle were those with the largest cross-sectional areas relative to other fibres within a given muscle. The force responses and Ca2+ transients recorded from this group of single fibres were found to be fairly uniform, which may suggest that a single type of fibre was isolated. In contrast, the physiological properties of isolated lumbricalis IV fibres were highly variable and thus represented more than one fibre type. PMID- 2254439 TI - Calcium regulated thin filaments from molluscan catch muscles contain a caldesmon like regulatory protein. AB - The thin filaments of the anterior byssus retractor muscle of the edible mussel Mytilus and the transluscent and opaque adductors of the oyster Crassostrea have been isolated and their properties investigated. We find that the thin filaments from all three muscles can activate skeletal muscle myosin ATPase in the presence of calcium but that the activity is inhibited in its absence. The filaments contain a protein which interacts with antibodies to vertebrate smooth muscle caldesmon on immunoblots. The antibodies relieve the inhibition of the thin filament-activated myosin MgATPase. They can also bundle the thin filaments. We conclude that a caldesmon-like protein is present in molluscan muscle. As in the vertebrate smooth muscle, it could act as part of a control mechanism in addition to the myosin regulatory system. Vertebrate smooth muscle caldesmon can crosslink actin and myosin and it has been suggested that it may in this way contribute to the latch state. A similar interaction may be involved in the catch mechanism in molluscan muscle. PMID- 2254440 TI - Mechanical properties of mammalian single smooth muscle cells. I. A low cost large range microforce transducer. AB - A transducer has been developed for measuring the minute forces generated during isometric contractions (1.0-10.0 microN) of single smooth muscle cells from the pig urinary bladder and the human uterus. In addition to its high sensitivity, resolution and stability (100 mV microN-1, and less than 0.1 microN and less than 2.0 microN h-1), the transducer features a very wide range (100-140 microN) with good linearity, enabling measurement of contractions as well as passive force length characteristics within one uninterrupted measurement session. Since the transducer features an independent and interchangeable force to displacement conversion system, different force ranges can be realized by inserting force conversion systems with different compliances. PMID- 2254441 TI - Mechanical properties of mammalian single smooth muscle cells. II. Evaluation of a modified technique for attachment of cells to the measurement apparatus. AB - A method is described for attaching isolated single smooth muscle cells to an apparatus designed for measuring the longitudinal forces developed passively and actively by the cell upon straining, electrical or pharmacological stimulation. Primary attachment of the cell is based on its natural negative surface charge in combination with a positive surface charge on the micro-tools used for attaching. Definite attachment is obtained by a knotting technique. Results show that this method of attachment is reliable and strong enough to withhold forces exceeding those necessary to break or tear the cell. Although this method allows relatively short cells to be attached (L greater than 80 microns). alternative methods e.g. glueing, are necessary to attach the shortest smooth muscle cells. PMID- 2254442 TI - Abstracts of the 1989 Annual Meeting on Muscle and Cell Motility Physiology. Tokyo, November 24-25, 1989. PMID- 2254443 TI - Preparing for the next generation. PMID- 2254445 TI - Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations. PMID- 2254444 TI - Nuclear thyroid hormone receptors. PMID- 2254447 TI - Developmental adaptations in cytosolic phosphate content and pH regulation in the sheep heart in vivo. AB - This study examines adaptations in myocardial cytosolic phosphate content and buffering capacity that occur in vivo as a function of development. Phosphate metabolites were monitored in an open chest sheep preparation using a 31P magnetic resonance surface coil over the left ventricle. Newborn lambs (aged 4-9 d, n = 5) underwent exchange transfusion with adult blood to reduce blood-borne 2,3-diphosphoglycerate contamination of the heart monophosphate and phosphomonoester resonances, thus allowing determination of these phosphate concentrations. The blood-exchanged newborns and mature controls (aged 30-60 d, n = 5) were infused with 0.4 N hydrochloric acid to decrease pH from greater than 7.35 to less than 7.00. Simultaneously, intracellular and extracellular pH were determined from the chemical shifts of the respective phosphate peaks and compared to arterial blood pH. Findings were as follows: (a) diphosphoglycerate contribution to the cardiac spectrum was found to be negligible, (b) significant decreases in cytosolic phosphate (P less than 0.03) and phosphomonoester (P less than 0.01) content occurred with maturation, and (c) large decreases in extracellular pH (greater than 0.5 U) in both groups were similarly associated with only small changes in intracellular pH (less than 0.1 U). Change in cytosolic phosphate content implies that alterations occur in the phosphorylation potential with resulting effects on regulation of myocardial respiration, and cardiac energetics. PMID- 2254446 TI - Lysis of complement-sensitive Entamoeba histolytica by activated terminal complement components. Initiation of complement activation by an extracellular neutral cysteine proteinase. AB - Activation of complement by Entamoeba histolytica may be initiated by the extracellular 56-kD neutral cysteine proteinase which cleaves the alpha chain of C3. To determine the relationship between the fluid-phase activation of complement and our observation that only strains isolated from patients with invasive disease are resistant to complement-mediated lysis, we investigated the fate of C3 with recent amebic isolates. When 125I-C3 was incubated with trophozoites in serum, C3 in the fluid phase was cleaved to C3b or C3bi, but the alpha chain of the C3 molecules on the cell surface appeared intact. Since the lysis of nonpathogenic strains takes place in the absence of bound C3b, we demonstrated that this reaction occurs by reactive lysis initiated in the fluid phase: (a) the killing of nonpathogenic strains was enhanced when alternative pathway activation was accelerated by the addition of cobra venom factor; (b) non pathogenic strains were lysed by purified terminal components; and (c) sera incubated with pathogenic E. histolytica produced passive lysis of chicken erythrocytes. These results demonstrate for the first time that complement sensitive E. histolytica are lysed by activation of the terminal complement components in the fluid phase where the 56-kD neutral cysteine proteinase cleaves C3, and not by the surface deposition of activated C3. PMID- 2254448 TI - Electrophysiological identification of alpha- and beta-intercalated cells and their distribution along the rabbit distal nephron segments. AB - By cable analysis and intracellular microelectrode impalement in the in vitro perfused renal tubule, we identified alpha- and beta-intercalated (IC) cells along the rabbit distal nephron segments, including the connecting tubule (CNT), the cortical collecting duct (CCD), and the outer medullary collecting duct in the inner stripe (OMCDi). IC cells were distinguished from collecting duct (CD) cells by a relatively low basolateral membrane potential (VB), a higher fractional apical membrane resistance, and apparent high Cl- conductances of the basolateral membrane. Two functionally different subtypes of IC cells in the CCD were identified based on different responses of VB upon reduction of the perfusate Cl- from 120 to 12 mM: the basolateral membrane of beta-IC cells was hyperpolarized, whereas that of alpha-IC cells was unchanged. This is in accord with the hypothesis that the apical membrane of beta-IC cells contains some Cl(-) dependent entry processes, possibly a Cl-/HCO3- exchanger. Further characterization of electrical properties of both subtypes of IC cells were performed upon lowering bath or perfusate Cl- from 120 to 12 mM, and raising bath or perfusate K+ from 5 to 50 mM. A 10-fold increase in the perfusate K+ had no effect on VB in both subtypes of IC cells. Upon abrupt changes in Cl- or K+ concentration in the bath, a large or a small depolarization of the basolateral membrane, respectively, was observed in both subtypes of IC cells. The electrical properties of alpha- and beta-IC cells were similar among the distal nephron segments, but their distribution was different: in the CNT, which consists of IC cells and CNT cells, 97.3% (36/37) of IC cells were of the beta type. In the CCD, which consists of IC cells and CD cells, 79.8% (79/99) of IC cells were of the beta-type, whereas in the OMCDi 100% (19/19) were of the alpha type, suggesting that the beta type predominates in the earlier and the alpha type in the later segment. PMID- 2254449 TI - Arterial baroreflex buffering of sympathetic activation during exercise-induced elevations in arterial pressure. AB - Static muscle contraction activates metabolically sensitive muscle afferents that reflexively increase sympathetic nerve activity and arterial pressure. To determine if this contraction-induced reflex is modulated by the sinoaortic baroreflex, we performed microelectrode recordings of sympathetic nerve activity to resting leg muscle during static handgrip in humans while attempting to clamp the level of baroreflex stimulation by controlling the exercise-induced rise in blood pressure with pharmacologic agents. The principal new finding is that partial pharmacologic suppression of the rise in blood pressure during static handgrip (nitroprusside infusion) augmented the exercise-induced increases in heart rate and sympathetic activity by greater than 300%. Pharmacologic accentuation of the exercise-induced rise in blood pressure (phenylephrine infusion) attenuated these reflex increases by greater than 50%. In contrast, these pharmacologic manipulations in arterial pressure had little or no effect on: (a) forearm muscle cell pH, an index of the metabolic stimulus to skeletal muscle afferents; or (b) central venous pressure, an index of the mechanical stimulus to cardiopulmonary afferents. We conclude that in humans the sinoaortic baroreflex is much more effective than previously thought in buffering the reflex sympathetic activation caused by static muscle contraction. PMID- 2254450 TI - Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis. AB - 125I-Serum amyloid P component (SAP), injected intravenously into 10 normal subjects, remained predominantly intravascular with mean (SD) T1/2 (half time) in plasma of 24.5 (5.9) h. The fractional catabolic rate of 68 (19)% of the plasma pool per day was more rapid than other reported human plasma proteins. All radioactivity was excreted in the urine by 14 d. In 16 patients with monoclonal gammopathy or chronic inflammatory diseases, but without amyloidosis, 125I-SAP metabolism was normal. However, among 45 patients with biopsy-proven systemic amyloidosis (25, amyloid A type; 20, amyloid L type), 125I-SAP was cleared from the plasma more rapidly, accumulated in the amyloid deposits, and persisted there. The T1/2 in amyloid, measured directly with 131I-SAP, was 24 d. Repeat studies after 6-18 mo were notably consistent in normals but changed significantly in amyloid patients, generally correlating with clinical signs of disease progression. Measurements of 125I-SAP turnover may thus be of value for diagnosis and monitoring of amyloidosis. Analysis of SAP metabolism in amyloidosis suggests that plasma SAP is in dynamic equilibrium with a very large amyloid pool, and in two autopsies the total mass of SAP in the amyloid deposits was 2,100 and 21,000 mg, respectively. PMID- 2254451 TI - A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure. AB - The most common deficiency allele of the plasma protease inhibitor alpha 1 antitrypsin (alpha 1AT) is PI*Z. Some rare deficiency alleles of alpha 1AT produce low but detectable amounts of plasma alpha 1AT (1-20% of normal), which can be differentiated by isoelectric focusing. Others, designated null (QO) alleles, produce no alpha 1AT detectable by routine quantitative methods. We have previously described a method using DNA polymorphisms, haplotypes, and polyacrylamide isoelectric focusing gels, to differentiate various deficiency alleles. Based on haplotypes, we previously identified, in eight patients, five different null alleles, four of which had been previously sequenced. We have now analyzed all 12 null alleles in these eight patients, using allele-specific oligonucleotide probes, and have identified six different null alleles. We have cloned and sequenced one of these, PI*QOludwigshafen, which has a base substitution in exon II, replacing isoleucine 92 in the normal sequence with an asparagine. This substitution of a polar for a nonpolar amino acid occurs in one of the alpha-helices and is predicted to disrupt the tertiary structure. A total of 13 different alpha 1AT deficiency alleles, 6 of them null alleles, have been sequenced to date. PMID- 2254452 TI - The core polypeptide of cystic fibrosis tracheal mucin contains a tandem repeat structure. Evidence for a common mucin in airway and gastrointestinal tissue. AB - A cystic fibrosis trachea cDNA library was constructed and probed with a synthetic oligonucleotide containing a consensus sequence recently identified in human intestinal mucin. One of the isolated clones, AMN-22, has been characterized extensively. The cDNA sequence of this 884-bp fragment was determined, and revealed a tandem repeat structure rich in threonine and proline residues. The repeating sequence of AMN-22 was similar but not identical to that determined for gut mucin. When examined by Northern analysis, the mRNA hybridizing to AMN-22 is extremely polydisperse in cystic fibrosis (CF) trachea, with apparent message length varying from approximately 2 kb to greater than 10 kb. A similar pattern was observed, with less abundant message, in CF bronchiectatic lung parenchyma. The lung cDNA hybridized to a similarly polydisperse message in ulcerative colitis colon RNA, but did not hybridize to control RNA from U937 lymphoma cells or stomach RNA. Pedigree analysis of restriction digests of genomic DNA revealed a pattern indicating a single polymorphic locus for the mucin gene expressed in the lung and the intestine. Southern analyses of human:mouse somatic cell hybrid cell lines allow a chromosomal localization for the mucin gene to human chromosome II, within the region 11p13-11pTer. Taken together, these data demonstrate that a polymorphic gene encodes a mucin core polypeptide expressed in both lung and intestine. PMID- 2254453 TI - Carbohydrate malabsorption. Its measurement and its contribution to diarrhea. AB - The major purpose of this research was to gain insight into the effect of carbohydrate malabsorption on fecal water output. To do this we measured daily fecal output of total carbohydrate, reducing sugars, and organic acids (a product of bacterial fermentation). Normal subjects were studied in their native state and when diarrhea was induced by mechanisms that did and did not involve carbohydrate malabsorption. Patients with malabsorption syndrome were also studied. We concluded that: (a) Excretion of carbohydrate and its breakdown products can be expressed as a single number by converting organic acids to their monosaccharide equivalents. (b) Diarrhea per se causes only a trivial increase in fecal carbohydrate excretion. (c) The molar output of osmotic moieties in feces due to unabsorbed carbohydrate can be determined by adding fecal reducing sugars to organic acids and their obligated cations. This expression parallels almost exactly the effect of increasing doses of lactulose (a nonabsorbable sugar) on fecal water output; one excreted millimole obligates 3.5 g of stool water. This relationship can be used to predict the effect of carbohydrate malabsorption on stool water output in patients with diarrhea. (d) 12 of 19 patients with malabsorption syndrome due to various diseases had excessive fecal excretion of carbohydrate and its breakdown products; of the diseases that cause malabsorption syndrome, combined small and large bowel resection is most likely to result in excessive fecal excretion of carbohydrate and monosaccharide equivalents. In 6 of these 19 patients carbohydrate malabsorption appeared to be the major cause of diarrhea. PMID- 2254455 TI - Recombinant latent transforming growth factor beta 1 has a longer plasma half life in rats than active transforming growth factor beta 1, and a different tissue distribution. AB - Transforming growth factor beta 1 (TGF-beta 1) is a key regulator of cell growth and differentiation. Under normal physiological conditions, it is made as a biologically latent complex whose significance is unknown. Previous work has indicated that active TGF-beta 1 has a very short plasma half-life in rats (Coffey, R. J., L. J. Kost, R. M. Lyons, H. L. Moses, and N. F. La-Russo. 1987. J. Clin. Invest. 80:750-757). We have investigated the possibility that latent complex formation may extend the plasma half-life of TGF-beta 1 and alter its organ distribution. Radiolabeled latent TGF-beta 1 was formed by noncovalent association of 125I-TGF-beta 1 with the TGF-beta 1 precursor "pro" region from recombinant sources. TGF-beta 1 in this latent complex had a greatly extended plasma half-life (greater than 100 min) in rats compared with active TGF-beta 1 (2-3 min). Whereas active TGF-beta 1 was rapidly taken up by the liver, kidneys, lungs, and spleen and degraded, TGF-beta 1 in the latent complex was largely confined to the circulation, and was less than 5% degraded after 90 min. The pharmacokinetics of TGF-beta 1 in the latent complex were shown to be critically dependent on the degree of sialylation of the complex. The results suggest that formation of latent complexes may switch endogenous TGF-beta 1 from an autocrine/paracrine mode of action to a more endocrine mode involving target organs distant from the site of synthesis. PMID- 2254454 TI - Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. AB - Cellular constituents of the alveolar-capillary wall may be key participants in the recruitment of polymorphonuclear leukocytes to the lung through the generation of the novel neutrophil chemotactic peptide interleukin-8 (IL-8). This interaction appears to occur via the ability of human alveolar macrophage (AM) derived monokines, tumor necrosis factor (TNF), and interleukin-1 (IL-1) to induce gene expression of IL-8 from pulmonary type II-like epithelial cells (A549). Northern blot analysis demonstrated that steady-state IL-8 mRNA expression, by either TNF- or IL-1 beta-treated A549 cells, occurred in both a dose- and time-dependent fashion. Similarly, extracellular antigenic IL-8, as assessed by specific ELISA, was expressed from TNF- or IL-1 beta-stimulated epithelial cells in a time-dependent fashion with maximal IL-8 antigen detected at 24 h poststimulation. Immunohistochemical staining utilizing rabbit anti-human IL-8 antibody identified immunoreactive, cell-associated IL-8 antigen as early as 8 h post-TNF or IL-1 beta stimulation. A549-generated neutrophil chemotactic bioactivity paralleled IL-8 steady-state mRNA levels. Signal specificity was demonstrated in this system as IL-8 mRNA or protein expression by lipopolysaccharide (LPS)-treated A549 cells was not different from unstimulated cells. Although LPS did not serve as a direct stimulus for the production of IL-8 by type II-like epithelial cells, the condition media from LPS-challenged AM induced a significant expression of IL-8 mRNA by the A549 cells. 24-h conditioned media from LPS-treated cells was as potent as either IL-1 beta or TNF in generating steady-state IL-8 mRNA by A549 cells. Preincubation of LPS-treated AM conditioned media with anti-human TNF or IL-1 beta neutralizing antibodies resulted in significant abrogation of IL-8 gene expression by A549 pulmonary epithelial cells. These findings demonstrate potential cell-to-cell communication circuits that may be important between AMs and pulmonary epithelial cells during the recruitment phase of acute lung inflammation. PMID- 2254456 TI - Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts. AB - Successful pancreas transplantation in type I diabetic patients restores normal fasting glucose levels and biphasic insulin responses to glucose. However, virtually no data from pancreas recipients are available relative to other islet hormonal responses or hormonal counterregulation of hypoglycemia. Consequently, glucose, glucagon, catecholamine, and pancreatic polypeptide responses to insulin induced hypoglycemia and to stimulation with arginine and secretin were examined in 38 diabetic pancreas recipients, 54 type I diabetic nonrecipients, and 26 nondiabetic normal control subjects. Glucose recovery after insulin-induced hypoglycemia in pancreas recipients was significantly improved. Basal glucagon levels were significantly higher in recipients compared with nonrecipients and normal subjects. Glucagon responses to insulin-induced hypoglycemia were significantly greater in the pancreas recipients compared with nonrecipients and similar to that observed in control subjects. Glucagon responses to intravenous arginine were significantly greater in pancreas recipients than that observed in both the nonrecipients and normal subjects. No differences were observed in epinephrine responses during insulin-induced hypoglycemia. No differences in pancreatic polypeptide responses to hypoglycemia were observed when comparing the recipient and nonrecipient groups, both of which were less than that observed in the control subjects. Our data demonstrate significant improvement in glucose recovery after hypoglycemia which was associated with improved glucagon secretion in type I diabetic recipients of pancreas transplantation. PMID- 2254457 TI - Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. AB - We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. PMID- 2254458 TI - Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. AB - To assess the mechanisms responsible for increased gluconeogenesis in noninsulin dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/ 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver. PMID- 2254459 TI - Role of intact cardiac nerves and reflex mechanisms in desensitization to catecholamines in conscious dogs. AB - To study chronic catecholamine desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 micrograms/kg/min) or saline over 3-4 wk in dogs instrumented with left ventricular (LV) pressure gauges and arterial and left atrial pressure catheters. An acute challenge to NE (0.4 micrograms/kg/min) in intact, conscious dogs increased LV dP/dt by 1,531 +/- 208 mmHg/s before NE pumps, and by a similar amount, 1,340 +/- 166 mmHg/s, 3-4 wk after NE pumps. In contrast, an acute challenge to isoproterenol (ISO, 0.4 micrograms/kg/min) increased LV dP/dt by 5,344 +/- 532 mmHg/s before NE pumps, and significantly less (P less than 0.05; 2,425 +/- 175 mmHg/s) after NE pumps. In the presence of ganglionic and alpha 1-adrenergic blockades, NE (0.4 micrograms/kg/min) increased LV dP/dt by 3,656 +/- 468 mmHg/s before NE pumps and significantly less (P less than 0.01; 1,459 +/- 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 micrograms/kg/min) in dogs with arterial baroreceptor denervation increased LV dP/dt by 3,732 +/- 896 mmHg/s before NE pumps, and significantly less (P less than 0.05, 1,725 +/- 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0.4 micrograms/kg/min) increased LV dP/dt by 9,901 +/- 1,404 mmHg/s before NE pumps and significantly less (P less than 0.01, 2,690 +/- 306 mmHg/s) after NE pumps. Desensitization of heart rate responses to NE challenge was also more apparent in the absence of reflex mechanisms. Thus, neural reflex mechanisms play a major role in physiological expression of cardiac desensitization to catecholamines in conscious dogs. PMID- 2254460 TI - Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production. AB - Recent studies suggest that vitamin A plays an inhibitory role with respect to "activation" of the hepatic Ito cell, a likely effector of hepatic fibrogenesis. Ito cell "activation" during fibrogenesis is characterized by a decrease in intracellular vitamin A and an increase in cellular proliferation and collagen production. To explore the hypothesis that retinoids have the capacity to diminish Ito cell activation, cultured Ito cells were exposed to retinoic acid and its effects assessed on three key features: cell proliferation, collagen protein production and mRNA abundance, and transforming growth factor beta protein production. Retinoic acid was 100-1,000X more potent than retinol with respect to inhibition of Ito cell proliferation. Interstitial collagen and transforming growth factor beta production were also reduced by 10(-6) M retinoic acid. The relative abundance of type I collagen mRNA however, was not significantly altered. By contrast, retinoic acid administration to rats caused a marked reduction in the abundance of type I collagen mRNA in both total hepatic and purified Ito cell RNA. The relative abundance of rat hepatic fibronectin or apolipoprotein E mRNA was not significantly altered. These studies demonstrate that retinoic acid can differentially modulate several key features of hepatic fibrogenesis in vitro and in vivo. PMID- 2254461 TI - Familial hypercatabolic hypoproteinemia. A disorder of endogenous catabolism of albumin and immunoglobulin. AB - The metabolism of albumin and IgG was investigated in two siblings, products of a first-cousin marriage, a female aged 34 yr and a male aged 17, who had a marked reduction in their respective serum concentrations of IgG (1.3 and 3.1 mg/ml) and albumin (19 and 21 mg/ml). The metabolism of radioiodinated IgG and albumin was studied in the two patients. The total circulating and body pools of IgG were less than 28% of normal. The IgG synthetic rates were within the normal range. However, the IgG survival was short, with their respective fractional catabolic rates increased fivefold to 31% and 36% of the intravenous pool per day (normal, 6.7 +/- 2%/d). Furthermore, the patients had reduced total body pools, normal synthetic rates, and increased fractional catabolic rates for albumin. There was no proteinuria or abnormality of renal or liver function. In addition, the patients did not have circulating antibodies directed toward IgG, IgA, or albumin. Furthermore, both patients had normal fecal 51Cr-labeled albumin tests, thus excluding excessive gastrointestinal protein loss. We propose that these siblings have a previously unrecognized familial disorder characterized by reduced serum concentrations of IgG and albumin caused by a defect in endogenous catabolism, leading to a short survival of these proteins that is associated in this family with chemical diabetes and a skeletal deformity. PMID- 2254462 TI - Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. AB - We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF. PMID- 2254463 TI - Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high molecular-weight-melanoma-associated antigen monoclonal antibodies. AB - In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma. PMID- 2254464 TI - Iron uptake by human upper small intestine microvillous membrane vesicles. Indication for a facilitated transport mechanism mediated by a membrane iron binding protein. AB - To investigate the hypothesis that iron absorption in man involves a carrier mediated cellular uptake mechanism, influx velocity (Vo) of 59Fe3+ by isolated human microvillous membrane (MVM) vesicles of the upper small intestine was examined. Vo revealed saturation kinetics (Km = 315 nM; Vmax = 361 pmol Fe3+ x min-1 x mg protein-1) was temperature dependent and inhibited by pronase pretreatment of MVM. In the presence of an inwardly directed Na(+)-gradient a typical overshoot phenomenon with maximal uptake at 30-40 s was observed. The suggestion of an active, carrier-mediated uptake mechanism for iron was pursued by isolation of a 160-kD iron-binding protein from solubilized human MVM proteins. This glycoprotein was assembled as a trimer composed of 54-kD monomers. A monospecific antibody against the 54-kD subunit inhibited vesicular influx of Fe3+ into MVM by greater than 50%. Immunofluorescence and immunoblot analysis confirmed the localization of the protein in brush border plasma membranes. It was detectable in human intestinal mucosa and liver, but not in esophagus. These data indicate that the translocation of Fe3+ across human MVM represents a facilitated transport mechanism which is, at least in part, mediated by a membrane iron-binding protein. PMID- 2254466 TI - Tissue expansion: past, present, and future. AB - The history of tissue expansion, technique, indications, and complications are reviewed. A detailed review of delayed tissue expansion's histologic, biochemical, biomechanical, and physiologic changes in the skin is given. There is a net gain in epidermal tissue during delayed expansion. Recent experimental and clinical experience suggests that expansion for 1 to 2 weeks is just as effective as longer delayed expansion for 6 to 8 weeks. A new deviation from standard technique, intraoperative tissue expansion, may have significant implications for dermatologic surgery. Intraoperative tissue expansion is explored in relation to other commonly used techniques of intraoperative load cycling. PMID- 2254465 TI - Hyperglycemia-induced B cell toxicity. The fate of pancreatic islets transplanted into diabetic mice is dependent on their genetic background. AB - The role of pancreatic B cell dysfunction in the phase preceding clinical onset of insulin-dependent and non-insulin-dependent diabetes mellitus has been much debated. In this investigation, the impact of a prolonged diabetic environment on pancreatic islet B cells transplanted syngeneically under the kidney capsule of C57BL/6 (B6) and C57BL/Ks (BKs) mice was studied. Alloxan-diabetic mice bearing a subcapsular islet graft insufficient to normalize the blood glucose level were rendered normoglycemic by a second intrasplenic islet graft after various period of hyperglycemia to examine the reversibility of hyperglycemia-induced B cell dysfunction. Using a perfusion technique of the graft-bearing, it was found that both strains of mice exhibited a diminished glucose-induced insulin secretion after 6 wk of hyperglycemia, when compared with normoglycemic mice carrying islet grafts. When normoglycemia was restituted by the splenic graft after 4 or 12 wk, there was a normalization of glucose-stimulated insulin secretion in the renal islet grafts in B6 mice, whereas insulin secretion from the grafted BKs islets remained impaired. Morphometric measurements of the islet grafts demonstrated a 50% reduction in the graft volume in diabetic BKs mice after 12 wk, compared with normoglycemic animals, whereas no such decrease was observed in B6 mice. Islet grafts removed from hyperglycemic mice of both strains exhibited diminished insulin mRNA contents, and in the BKs mice there was also a reduced glucose oxidation rate in the islet grafts in vitro. This metabolic dysfunction can only partly be explained by a reduced graft size. The present findings emphasize the genetic constitution as a decisive factor for the survival and function during a period of sustained stress on a limited B cell mass. PMID- 2254467 TI - Clinical association of autoantibodies to fibrillarin with diffuse scleroderma and disseminated telangiectasia. AB - Circulating autoantibodies against a variety of nuclear and nucleolar antigens are characteristic serologic findings in systemic scleroderma. Some of these antibodies correlate with clinical subsets of the disease. We describe three patients with systemic scleroderma and high autoantibody titers against U3 ribonucleoprotein-associated fibrillarin, a recently identified 34 kD nucleolar protein. These patients showed a progressive course with multiple organ and diffuse skin involvement with disseminated telangiectasia. PMID- 2254468 TI - Spitz nevi in black children. AB - Four black children with Spitz nevi are presented. The initial clinical diagnosis was pyogenic granuloma for three patients. One child had two Spitz nevi. Histologic examination revealed melanocytic dendritic hyperplasia in all cases. PMID- 2254469 TI - Composition of cerumen lipids. AB - Lipids were extracted from "wet" cerumen and analyzed by quantitative thin-layer chromatography to determine their composition. The lipid fraction comprised 52% of the dry weight of cerumen and consisted of squalene (6.4%), cholesterol esters (9.6%), wax esters (9.3%), triacylglycerols (3.0%), fatty acids (22.7%), cholesterol (20.9%), ceramides (18.6%), cholesterol sulfate (2.0%), and several unidentified polar components (7.5%). In addition to the extractable lipids, the residue contained an additional 0.9% lipid that could be released only after saponification. This covalently bound lipid consisted of two unusual ceramides (63.4%), omega-hydroxyacids (27.7%) and nonhydroxy fatty acids (8.8%). The composition of this bound lipid resembled that recently found in human stratum corneum, which is thought to comprise a lipid envelope on the outer surface of the corneocytes. The free and covalently bound lipids may be significant determinants of the properties of cerumen. Desquamation of corneocytes and their associated lipids from the epidermal lining of the ear canal may make a major contribution to cerumen. PMID- 2254470 TI - Ocular melanoma in families with dysplastic nevus syndrome. AB - Five families with the dysplastic nevus syndrome, in each of which one member had ocular melanoma, are reported. These five families were examined within a 3-year period in one medical center. To date only five other families with such a combination have been reported. We suggest a causal relation between ocular melanoma and the familial dysplastic nevus syndrome. PMID- 2254471 TI - Multiple keratoacanthomas treated with oral retinoids. AB - Multiple eruptive keratoacanthoma of Witten and Zak is a rare disorder characterized by numerous small, eruptive tumors and larger, more typical keratoacanthomas. Affected patients have features of Grzybowski-type keratoacanthomas and Ferguson Smith type. Two patients with multiple keratoacanthomas were treated with oral retinoids. Both patients had hundreds of follicular papules on the trunk and extremities. Less common lesions included nodules with central horn-filled craters more characteristic of classic keratoacanthomas. Retinoid therapy resulted in regression of the larger, more typical keratoacanthomas in both patients. The small follicular keratoacanthomas remained unaffected. Thus oral retinoids are only partially beneficial for the treatment of the Grzybowski type or the Witten and Zak type of multiple eruptive keratoacanthomas. PMID- 2254472 TI - Toxic epidermal necrolysis after bone marrow transplantation: study of nine cases. AB - Acute graft-versus-host reaction after allogeneic bone marrow transplantation has been reported to induce toxic epidermal necrolysis. To assess the respective role of acute graft-versus-host disease and of drug reaction in this setting, we retrospectively reviewed nine cases of toxic epidermal necrolysis that occurred in a series of 152 allogenic bone marrow recipients. In five cases visceral involvement was suggestive of acute graft-versus-host disease without any drug more than "doubtfully" suspected. In four cases extracutaneous symptoms were absent or mild and suspect drugs (mainly sulfonamides) had been administered with a timing suggestive of "possible" causality. All nine patients died, mainly from infection possibly aggravated by high doses of corticosteroids. We conclude that toxic epidermal necrolysis may be more frequent than generally thought after bone marrow transplantation and has a poor prognosis. It seems to be related to a drug reaction to sulfonamides as often as to acute graft-versus-host disease. PMID- 2254473 TI - Molecular identification of major and minor bullous pemphigoid antigens. AB - The skin antigens defined by basement membrane zone antibodies in 38 patients with bullous pemphigoid were analyzed by Western immunoblot. Thirty-four patients (89%) had antibodies to a major bullous pemphigoid antigen with a molecular weight of approximately 230 kD. Twelve patients (32%) had antibodies to a minor bullous pemphigoid antigen with a molecular weight of approximately 160 kD; this included four patients who did not have antibodies to the 230 kD antigen. Depending on the epidermal extract used, a variable number of patients (up to 75%) also had antibodies to minor bullous pemphigoid antigens with molecular weights of approximately 180 and 200 kD. The results of this study confirm that bullous pemphigoid antigens are heterogeneous at the molecular level. Approximately 10% of patients have antibodies directed solely to a minor bullous pemphigoid antigen. PMID- 2254474 TI - Polypoid melanoma: a virulent variant of nodular melanoma. Report of three cases and literature review. AB - We report the cases of three patients with polypoid melanoma. In no case was there microscopic evidence of melanoma cell invasion below the papillary dermis. In the polypoid variant of nodular melanoma, melanoma cells accumulate in large volume above the skin's surface. This increase in tumor volume encourages dislodgment of melanoma cells that are carried to superficial lymphatic vessels without invading the reticular dermis; this feature differentiates polypoid melanoma from the nonpolypoid nodular variant. Although polypoid melanoma is considered the most malignant form of melanoma, our findings, albeit limited to three cases, suggest that early diagnosis and prompt surgical excision may provide a favorable 5-year survival rate. PMID- 2254475 TI - Colony-stimulating factors. AB - Recombinant hematopoietic colony-stimulating factors have profound effects on developing and mature granulocytes, macrophages, and lymphocytes. Use of these agents for treatment of disease may result in a variety of adverse cutaneous reactions. The recent discovery of colony-stimulating factor production by keratinocytes and dermal cells suggests that these agents may also be significant in cutaneous homeostasis and in the pathogenesis of cutaneous diseases. PMID- 2254476 TI - Digital imaging techniques in dermatology. AB - Digital imaging is a versatile technique that has been infrequently used in dermatology to record visual images. We have used this technology for 10 patients to follow cutaneous lesions, including alopecia mucinosa, psoriasis, and dysplastic nevi. The setup included a personal computer, digitizer board, monitor, video camera, and lights. An introduction to electronic (digital) imaging is given and some of the many possible applications in dermatology are discussed. PMID- 2254477 TI - The early dermatologists of Guy's Hospital. PMID- 2254478 TI - Rapid response of von Zumbusch psoriasis to cyclosporine. PMID- 2254479 TI - Aluminum chloride hexahydrate and blistering in epidermolysis bullosa simplex. PMID- 2254480 TI - Serum 8-methoxypsoralen (8-MOP) concentrations after bath water delivery of 8-MOP plus UVA. PMID- 2254481 TI - Use of alpha-hydroxy acids in the therapy for 'photoaged' skin. PMID- 2254482 TI - Treatment of solitary keratoacanthomas with oral isotretinoin. PMID- 2254483 TI - Topical cyclosporine for oral bullous disorders. PMID- 2254484 TI - Tryptophan-induced eosinophilic fasciitis. PMID- 2254485 TI - Pyoderma gangrenosum associated with Behcet's disease: treatment with thalidomide. PMID- 2254486 TI - Neutrophilic eccrine hidradenitis in HIV-infected patients. Armed Forces Retrovirus Research Group. PMID- 2254487 TI - Successful treatment of a patient with cutaneous malacoplakia with clofazimine and trimethoprim-sulfamethoxazole. PMID- 2254488 TI - Dermatology and the new genetics--a plea. PMID- 2254489 TI - Treatment of lymphedema with multicompartmental pneumatic device. PMID- 2254490 TI - Compression for lymphedema and cellulitis. PMID- 2254491 TI - Exchange of prescription medications by dermatology outpatients. PMID- 2254492 TI - Multiple moles and melanoma risk. PMID- 2254493 TI - Topical corticosteroid compounding. PMID- 2254494 TI - Lichen planus pigmentosus. PMID- 2254495 TI - Occurrence of a melanoma in a young man being treated for psoriasis. PMID- 2254496 TI - Oral hairy leukoplakia in HIV-negative immunosuppressed patients. PMID- 2254497 TI - Loss, widowhood, and psychological distress among the elderly. AB - Psychological response to recent nonspousal familial loss was examined in a sample of elderly men and women (N = 825). Loss was related to a higher level of depressive symptomatology in men, but not women. Both the presence of a spouse and membership in a church or temple moderated the impact of loss on depression among men, such that widowed men who experienced a loss, and men who experienced a loss and did not belong to a church/temple, showed elevated depression scores. Widowed men who experienced recent nonspousal familial loss and did not belong to a church/temple were most depressed of all, with fully 100% of the respondents with these characteristics scoring above the cutpoint for depression established in community studies. Discussion centers on the role of social ties in buffering distress and gender differences in coping with stress. Outreach by churches/temples and other community organizations is suggested as appropriate intervention. PMID- 2254498 TI - Improved obstetric outcomes using hypnotic analgesia and skill mastery combined with childbirth education. AB - The benefits of hypnotic analgesia as an adjunct to childbirth education were studied in 60 nulliparous women. Subjects were divided into high and low hypnotic susceptibility groups before receiving 6 sessions of childbirth education and skill mastery using an ischemic pain task. Half of the Ss in each group received a hypnotic induction at the beginning of each session; the remaining control Ss received relaxation and breathing exercises typically used in childbirth education. Both hypnotic Ss and highly susceptible Ss reported reduced pain. Hypnotically prepared births had shorter Stage 1 labors, less medication, higher Apgar scores, and more frequent spontaneous deliveries than control Ss' births. Highly susceptible, hypnotically treated women had lower depression scores after birth than women in the other 3 groups. We propose that repeated skill mastery facilitated the effectiveness of hypnosis in our study. PMID- 2254499 TI - Use of mental health services among victims of crime: frequency, correlates, and subsequent recovery. AB - The use of mental health services was examined within a sample of 392 victims of crime who were generally representative of that population in Kentucky. Respondents were interviewed twice at a 6-month interval. Of these victims, 12% had contact with mental health professionals within the first few months postcrime. Hierarchical discriminant analyses revealed that use of mental health services was most prevalent when depressive symptoms were present and the crime involved violence. Among victims of violence, urban residence, high social support, internal locus of control, and prior crime experience were also associated with use. The victims who recovered from the event most rapidly were those who reported receiving mental health services at both Waves 1 and 2. Implications of the study for policies and programs are discussed. PMID- 2254500 TI - Psychological distress among Mexican-American and Mexican women as related to status on the new immigration law. AB - Psychological distress in relation to the 1986 Immigration Reform and Control Act was examined among 90 Mexican-American and Mexican women divided into three groups (n = 30 each): undocumented immigrants who did not qualify for amnesty, undocumented immigrants who qualified for amnesty, and legal residents of the United States of Mexican descent. Results indicate that the undocumented immigrants who did not qualify for amnesty obtained significantly higher scores on hostility. Contrary to prediction, undocumented immigrants who qualified for amnesty obtained lower scores in anxiety (a statistical trend) than did the other two groups. No differences in global psychological distress were found between the undocumented immigrants and the legal residents. PMID- 2254501 TI - Cognitive style and pleasant activities among female adolescent suicide attempters. AB - Cognitive style and pleasant activities of 77 suicide-attempting female minority adolescents were compared with those of 2 groups of non-suicide-attempting female minority adolescents, 39 who were psychiatrically disturbed and 23 who were nondisturbed. Suicide attempters differed from other groups, even when depression and IQ were statistically controlled. They reported significantly fewer alternatives for solving interpersonal problems, were significantly more focused on problems, and were more likely to report a wishful thinking style of coping in stressful situations than were members of the nondisturbed comparison group. Across groups, depression was associated with significantly more dysfunctional attributions. Interpersonal problem-solving ability and attributional style best distinguished the suicide attempters. Results suggest using different cognitive behavioral interventions with depressed and nondepressed minority female adolescent suicide attempters. PMID- 2254502 TI - Problem-solving deficits in suicidal patients: trait vulnerability or state phenomenon? AB - A diathesis-stress model has been proposed (Schotte & Clum, 1982, 1987), in which deficits in interpersonal problem-solving skills are said to predispose individuals under chronic stress to depression, hopelessness, and suicide ideation. The present study examined the stability of interpersonal problem solving skills in a short-term, longitudinal study of hospitalized suicide ideators (N = 36). The Ss displayed marked changes in depressive symptoms, state anxiety, hopelessness, and suicide intent over time, and these improvements were associated with improvements in interpersonal problem-solving skills. It is concluded that interpersonal problem-solving deficits may be a concomitant, rather than a cause, of depression, hopelessness, and suicide intent. PMID- 2254503 TI - Behavioral intervention to reduce child and parent distress during venipuncture. AB - This study investigated a behavioral intervention incorporating parent coaching, attentional distraction, and positive reinforcement to control child distress during invasive cancer treatment. Children (N = 23) requiring physical restraint to complete venipuncture were alternately assigned to either a behavioral intervention or an attention control condition. Child distress behaviors were recorded, and self-reports of parent, child, and nurse distress were obtained. Parent and nurse also rated child distress. Results of planned comparisons indicate that observed child distress, parent-rated child distress, and parent ratings of his/her own distress were significantly reduced by behavioral intervention and were maintained across the course of three intervention trials. The use of physical restraint to manage child behavior was also significantly reduced. Child self-reported pain and nurse ratings of child distress were not significantly affected. PMID- 2254504 TI - The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. AB - One hundred hyperactive children meeting research diagnostic criteria and 60 community control children were followed prospectively over an 8-year period into adolescence. Younger (12-14 years) and older (15-20 years) groups were tested on measures of academic skills, attention and impulse control, and select frontal lobe functions. At follow-up, hyperactive Ss demonstrated impaired academic achievement, impaired attention and impulse control, and greater off-task, restless, and vocal behavior during an academic task, compared with control Ss. The limited set of frontal lobe measures did not differentiate the groups. Age did not interact with group membership. However, several measures showed age related declines in both groups. It is concluded that hyperactive children may remain chronically impaired in academic achievement, inattention, and behavioral disinhibition well into their late adolescent years. PMID- 2254505 TI - Intellectual ability and achievement in psychiatrically hospitalized children with conduct, anxiety, and affective disorders. AB - The IQ and academic achievement of psychiatrically hospitalized children were studied. The sample consisted of 76 children, with a mean age of 10 years, who received diagnoses of conduct, oppositional, anxiety, and affective disorders on the basis of a structured diagnostic interview. A relative deficit in verbal abilities was observed for conduct-disordered children, extending to pre adolescents the findings previously obtained for adolescent delinquents. Depressed children were characterized by underachievement, which is consistent with the learned helplessness literature. Contrary to expectations, children with an anxiety disorder had a lower IQ than children without the disorder. No cognitive deficits were observed for children diagnosed as oppositional. PMID- 2254507 TI - Effects of language usage on the emotional experience of Spanish-English and English-Spanish bilinguals. AB - This study assessed the effects of the mother tongue and the second tongue on the affective experience of 80 English-Spanish and Spanish-English coordinate bilinguals. Ss were randomly assigned to a mother tongue condition or a 2nd language condition. It was predicted that Ss would express more affect in their mother tongue. Results of a MANCOVA revealed a statistically significant interaction in which English-Spanish bilinguals expressed more affect in their 2nd language (Spanish) and Spanish-English bilinguals expressed more affect in their mother tongue (Spanish). That is, all Ss answered with significantly greater affect in the Spanish language condition, and they differed in levels of anxiety and depression depending on which language they were using. Implications are discussed for the psychological assessment of bilinguals as well as for psychotherapy. PMID- 2254506 TI - Adolescents' subjective distress over their emotional/behavioral problems. AB - This study analyzed the relations among 151 7th- and 8th-grade adolescents' self evaluations of the occurrence of their behavior, their own subjective distress over their behavior, their perceptions of their personal competence, their perceptions of their mothers' and fathers' distress over these behaviors, and their parents' reports of the occurrence of adolescent behaviors. As hypothesized, adolescents' self-reports of occurrence of their behaviors were significantly but moderately correlated with their subjective distress about these behaviors, and adolescents made a distinction between the occurrence of a behavior and their distress about it. Externalizing behaviors were rated by adolescents as more distressing to mothers and to fathers than to adolescents themselves, and conversely, internalizing behaviors were rated as more distressing to self than to parents. Ratings of subjective distress were significantly related to self-perceptions of behavioral conduct and self-worth, whereas parents' ratings of the occurrence of behavior were not related to these self-perceptions. PMID- 2254508 TI - Predictive validity of therapeutic alliance in group marital therapy. AB - The relation between marital distress, therapeutic alliance formation, and treatment outcome was investigated in a group marital skills training program in which 63 couples met for 9 weekly 3-hr sessions. Treatment outcome was assessed before and after completion of treatment through a series of self-report measures. The quality of the therapeutic alliance as viewed by the couples and the therapists was monitored at the 3rd session. Results indicate that levels of marital distress neither impaired nor facilitated alliance formation. In addition, it was demonstrated that patients' and therapists' ratings of the strength of the therapeutic alliance constitute a determinant of successful treatment. It appears, however, that the strength of the alliance is a more powerful predictor of therapeutic success among men than among women. PMID- 2254509 TI - Thinking about thinking in therapy: an examination of clients' understanding of their therapists' intentions. AB - Two therapists each provided 2 clients time-limited (10 sessions each) therapies. These were examined to discover relations between (a) clients' understanding of therapists' intentions and episode level outcome, (b) similarities and differences between the participants' valuing of different intentions, and (c) shifts in intentions valued from the beginning to the terminal phases of therapy. By using therapists' segmentation of sessions into episodes and a computerized Counselor Intention List, some positive relations between clients' understanding of counselor intention and episode impact were documented. Differences were found between therapists' and clients' valued intentions as were systematic shifts in valued intentions from beginning to end phases of therapy. PMID- 2254510 TI - Identification of patients at risk for nonresponse and negative outcome in psychotherapy. AB - This study evaluated the use of pretherapy patient variables as correlates of 3 categorical types of outcome: negative response (negative change of more than 1 normative SEest on depression measure); nonresponse (change within +/- 1 SEest on depression measure); and positive response (positive change of more than 1 SEest on depression measure) to psychotherapy among 62 patients with major depressive disorder. By using 4 scales from the Brief Symptom Inventory, the Inventory of Interpersonal Problems, age, and sex, 75.8% of the Ss were correctly classified into the 3 groups. Negative responders were characterized by high levels of interpersonal difficulty and low levels of subjective distress. Nonresponders displayed moderate levels of both interpersonal difficulties and subjective distress. Positive responders displayed high levels of both interpersonal difficulties and subjective distress. PMID- 2254511 TI - Group cognitive-behavioral treatment for the nonpurging bulimic: an initial evaluation. AB - This study tested the initial effects of cognitive-behavioral therapy for binge eating in Ss who do not purge. Forty-four female binge eaters were randomized to either cognitive-behavioral treatment (CB) or a waiting-list (WL) control. Treatment was administered in small groups that met for 10 weekly sessions. At posttreatment a significant difference was found, with 79% of CB Ss reporting abstinence from binge eating and a 94% decrease in binge eating compared with a nonsignificant reduction (9%) in binge eating and zero abstinence rate in WL Ss. Following the posttest assessment, WL Ss were treated and evidenced an 85% reduction in binge episodes and a 73% abstinence rate. Binge eating significantly increased at 10-week follow-up for initially treated Ss; however, the frequency remained significantly improved compared with baseline levels. PMID- 2254512 TI - Supplementing behavioral marital therapy with cognitive restructuring and emotional expressiveness training: an outcome investigation. AB - The current study investigated whether the effectiveness of behavioral marital therapy (BMT) would be increased by the addition of cognitive restructuring (CR) and/or emotional expressiveness training (EET) for maritally distressed couples. Sixty such couples were randomly assigned to 1 of 3 therapists and 1 of 5 treatment conditions (BMT Alone, CR + BMT, BMT + EET, CR + BMT + EET, or waiting list) for 12 weeks of conjoint marital therapy. Within each treatment condition, couples typically improved on the variables focused on in treatment. However, comparisons among active treatment conditions showed few significant differences among treatments; the treatments were equally effective in increasing marital adjustment. Thus, the addition of CR and EET did not appear to increase the overall effectiveness of treatment. Possible reasons for the current findings are provided, and suggestions for future marital outcome investigations are outlined. PMID- 2254513 TI - Statistical power of psychological research: what have we gained in 20 years? AB - Power was calculated for 6,155 statistical tests in 221 journal articles published in the 1982 volumes of the Journal of Abnormal Psychology, Journal of Consulting and Clinical Psychology, and Journal of Personality and Social Psychology. Power to detect small, medium, and large effects was .17, .57, and .83, respectively. 20 years after Cohen (1962) conducted the first power survey, the power of psychological research is still low. The implications of these results concerning the proliferation of Type I errors in the published literature, the failure of replication studies, and the interpretation of null (negative) results are emphasized. An example is given of the use of power analysis to help interpret null results by setting probable upper bounds on the magnitudes of effects. Limitations of statistical power analyses, suggestions for future research, sources of computational information, and recommendations for improving power are discussed. PMID- 2254514 TI - Psychosocial functioning of learning-disabled children: relations between WISC Verbal IQ-Performance IQ discrepancies and personality subtypes. AB - A total of 132 children with learning disabilities (LD) between the ages of 6 and 12 years were divided equally into 3 groups on the basis of the difference between WISC VIQ-PIQ scores (viz., VIQ greater than PIQ, VIQ = PIQ, and VIQ less than PIQ). The mean Personality Inventory for Children (PIC) profiles for the VIQ = PIQ and VIQ less than PIQ groups were normal; however, the VIQ greater than PIQ group showed pathological elevations on some PIC scales. Group average linkage cluster analysis using 10 PIC scales revealed 6 psychosocial subtypes. Within these subtypes, children with VIQ greater than PIQ were found at lower than expected frequencies in normal and mildly disturbed subtypes, but at higher than expected frequencies in seriously disturbed subtypes. These results support the notion that patterns of cognitive performance are related to patterns of psychosocial functioning in children with LD. PMID- 2254515 TI - Five-year follow-up of family-based behavioral treatments for childhood obesity. AB - This article presents the 5-year outcome of family-based behavioral treatment of obesity for 6- to 12-year-old children in 162 families across 4 treatment outcome studies. Results suggest that treatments that use (a) conjoint targeting and reinforcement of child and parent behavior or (b) reciprocal targeting and reinforcement of children and parents are associated with the best child outcomes. Predictors of child success include self-monitoring, changing eating behavior, praise, and change in parent percent overweight. Parental outcome is predicted by self-monitoring weight, baseline parent percent overweight, and participation in fewer subsequent weight control programs. PMID- 2254516 TI - Two-year follow-up of bibliotherapy for depression in older adults. AB - The present study examined the long-term benefits of participation in a bibliotherapy program for depressed older adults. Thirty of the original 44 participants (68%) were assessed at approximately 2 years following treatment for clinician-rated and self-rated depression. There were no significant increases in either index suggesting that improvements were maintained. Follow-up questions revealed that most participants (77%) had not received other treatment, most (73%) felt their depression level had decreased, and over half (53%) had read at least parts of their assigned book during the 2-year interval. Results further support the potential for structured bibliotherapy as a treatment adjunct or alternative. PMID- 2254517 TI - An academy of editors. PMID- 2254518 TI - Nursing history and scholarship--critical issues for the discipline. PMID- 2254519 TI - A summing up--the message of health for all. PMID- 2254520 TI - Living wills--controversy and certainty. PMID- 2254521 TI - Shortage and standards--an incompatible duo? PMID- 2254522 TI - In a clinical voice.... PMID- 2254523 TI - Promoting more effective health care--the role of nursing. PMID- 2254525 TI - Education. Back to basics. PMID- 2254524 TI - Agency for Health Care Policy and Research--a challenge for nurse researchers. PMID- 2254526 TI - Nurse practitioners: leadership behaviors and organizational climate. AB - The purpose of this article is to examine the relationships of individual nurse practitioners' perceptions of the leadership climate in their organizations and self-reported formal and informal leadership behaviors. The nine climate dimensions (Structure, Responsibility, Reward, Perceived Support of Risk Taking, Warmth, Support, Standard Setting, Conflict, and Identity) identified by Litwin and Stringer in 1968 were used to predict five leadership dimensions (Meeting Organizational Needs, Managing Resources, Leadership Competence, Task Accomplishment, and Communications). Demographic variables of age, educational level, and percent of time spent performing administrative functions were forced as a first step in each multiple regression analysis and used to explain a significant amount of variance in all but one analysis. All leadership dimensions were predicted by at least one organizational climate dimension: (1) Meeting Organizational Needs by Risk and Reward; (2) Managing Resources by Risk and Structure; (3) Leadership Competence by Risk and Standards; (4) Task Accomplishment by Structure, Risk, and Standards; and (5) Communication by Rewards. PMID- 2254527 TI - The validity of ACT-PEP test scores for predicting academic performance of registered nurses in BSN programs. AB - This study investigated the validity of three American College Testing Proficiency Examination Program (ACT-PEP) tests (Maternal and Child Nursing, Psychiatric/Mental Health Nursing, Adult Nursing) for predicting the academic performance of registered nurses (RNs) enrolled in bachelor's degree BSN programs nationwide. This study also examined RN students' performance on the ACT-PEP tests by their demographic characteristics: student's age, sex, race, student status (full- or part-time), and employment status (full- or part-time). The total sample for the three tests comprised 2,600 students from eight institutions nationwide. The median correlation coefficients between the three ACT-PEP tests and the semester grade point averages ranged from .36 to .56. Median correlation coefficients increased over time, supporting the stability of ACT-PEP test scores for predicting academic performance over time. The relative importance of selected independent variables for predicting academic performance was also examined; the most important variable for predicting academic performance was typically the ACT-PEP test score. Across the institutions, student demographic characteristics did not contribute significantly to explaining academic performance, over and above ACT-PEP scores. PMID- 2254528 TI - A critical review of human immunodeficiency virus infection--and acquired immunodeficiency syndrome-related research: the knowledge, attitudes, and practice of nurses. AB - This article reviews the research literature related to nurses' knowledge, attitudes, and practices (KAP) concerning acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection, and care of people with AIDs (PWAs). Areas reviewed included the following: (1) KAP studies of health professionals that include nurses; (2) KAP studies of nurses; (3) KAP studies of nursing students and faculty; (4) studies of stress and coping related to care of PWAs; and (5) studies of outcomes of AIDS education programs. Gaps in knowledge and negative, fearful attitudes toward HIV transmission and PWAs were identified. Negative fears and behaviors decreased in nurses with the gain in accurate information. The studies were largely atheoretical descriptive surveys of health professionals in acute care settings. Studies of nurses specifically, including more studies of obstetric and pediatric nurses, and nurses in a range of settings in the community would be beneficial both in the United States and in other countries. A wider variety of research designs including qualitative studies are needed as are valid and reliable instruments to allow for cross-comparisons between studies. An assessment of non-AIDS-related content, such as spiritual needs of patients and substances abuse is needed by nurses who care for PWAs for use in development of relevant educational programs. PMID- 2254529 TI - Mental status change in the elderly: recognizing and treating delirium. AB - Delirium is a common cause of acute mental status change in hospitalized elderly people, yet the literature and the author's clinical experience suggest that clinical nurses are often unaware of how the syndrome can present, how it differs from other types of mental status changes seen in the elderly, and what interventions are most appropriate in affected individuals. This article discusses these areas, presents original data from a study at Beth Israel Hospital, Boston, MA, concerning nursing assessment of patients with delirium, and outlines a new educational module that nurse specialists, educators, and others can use to teach clinical nurses about delirium in elderly patients. PMID- 2254530 TI - Preserve our commitment to professionalism. PMID- 2254531 TI - The dental policy perspective. PMID- 2254532 TI - Ethics everywhere everyday: a perspective. PMID- 2254533 TI - The ACD is a catalyst for the profession. PMID- 2254534 TI - Lessons to be learned from Pierre Fauchard. AB - Pierre Fauchard possessed the following attributes: Curiosity, intelligence, courage, perseverance, honesty, dexterity, and social responsibility. I suspect that these qualities would have assured him success in whatever career he might have followed. He chose surgery, and through his experience as a ship's doctor in the French navy, he specialized in diseases of the mouth and teeth (common among seamen), qualifying as a surgeon-dentist prior to establishing his highly successful private practice in Paris. In his long career he stood for excellence, the scientific approach, comprehensive care, high ethical standards, and technical innovation. Although we know almost nothing of his private life, his book does reveal a good part of his character. Based solely on this source it is possible to conclude that Fauchard was a true son of the enlightenment, who justifiably holds the title of Father of Modern Dentistry. His treatise contains lessons to be emulated even into the 21st century. PMID- 2254535 TI - Update on tenure in U.S. and Canadian dental schools. PMID- 2254536 TI - The anniversary year: Part III. The ACD role in dental journalism. AB - Thus, the challenge to proprietary dental journalism was made and corrective action presented. The Journal of Dental Research was identified as a model and given encouragement and support. The Journal of the American College of Dentists became a regular part of the dental literature. The College established formal relations with the American Association for the Advancement of Science and the College indirectly gave birth through the W.J. Gies Endowment Fund for the Journal of Dental Research to the William J. Gies Foundation for the Advancement of Dentistry, Inc. These actions crossed all disciplines of the dental profession and in the 1930's identified the College as an organization to be reckoned with for professional matters. J. Ben Robinson stated it very well in his Presidential Address on the afternoon of November 3rd, 1935: "The College, from its modest beginning fifteen years ago, has rapidly and substantially grown to occupy an important place in the profession. As its duty has become clearer, and its responsibilities better understood, additional problems have been accepted and assigned to committees for investigation, study and report. The ensuing results have contributed materially to the advancement of the profession by clarifying thought, establishing sound trends of endeavor, and strengthening the positions of dentistry in many important relations... The American College of Dentists exist for the prime purpose of fostering professionalism as an ideal, and of promoting education, literature, and organization along lines that will ensure high standards in all relations....(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254538 TI - Integrity is part of the treatment plan. PMID- 2254537 TI - Dentist football coaches. PMID- 2254539 TI - ACC/AHA guidelines for the clinical application of echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Clinical Application of Echocardiography). PMID- 2254540 TI - Coronary angioplasty in young adults: initial results and late outcome. AB - The initial and late outcome of coronary angioplasty was studied in 148 patients less than 40 years of age (mean 36.4 +/- 3). Angioplasty was performed on a single vessel in 70% of patients and on multiple vessels in 30%; it was performed on a totally occluded vessel in 20%. Angioplasty was successful in 90.5% of patients, unsuccessful but uncomplicated in 7.4% and complicated by myocardial infarction in 0.7%, emergency bypass surgery in 0.7% and death in 0.7%. At late (mean 3.7 +/- 3 years; range 0.5 to 11.5) follow-up study after successful angioplasty, 94% of patients were alive, 79% were free of angina and 85% had returned to work; late myocardial infarction occurred in 4%. Actuarial survival at 5 years was 95%, and 85% of patients were free from death, infarction or bypass surgery. A second angioplasty was performed in 29 patients (22%) (mean 6.1 +/- 8.4 months) and was successful in 27 (93%), with no deaths. Elective coronary bypass surgery was performed in 8.5% of patients, with perioperative infarction in 9% and no deaths. By univariate analysis, late death was more likely to occur in hypertensive patients (15% versus 2.5%; p less than 0.01) and diabetic patients (21.4% versus 3.6%; p less than 0.01). Cox proportional hazard regression analysis identified hypertension (p = 0.007) and diabetes (p = 0.04) as independent time-related predictors of subsequent death. Thus, early and late results after coronary angioplasty in young adults are favorable, but certain risk factors are important predictors of outcome. Late revascularization procedures (repeat angioplasty or surgery) for restenosis or disease progression are common. PMID- 2254541 TI - Decreased operative risk of surgical treatment of mitral regurgitation with or without coronary artery disease. AB - The consecutive 2 year experience with patients undergoing first-time surgery for mitral regurgitation with and without coronary artery disease was reviewed. From January 1988 to January 1990, 127 patients with pure mitral regurgitation undergoing first-time operation were surgically treated. No other valve lesion, no reoperation and no congenital defects were included. The mean patient age was 62 years with 26% of the patients greater than 70 years. Twenty-six percent of the entire group was in functional class IV. Seventy-five patients received mitral valve repair and 52 underwent mitral valve replacement with a St. Jude or Hancock valve. In patients undergoing mitral valve repair, there was a higher incidence of those greater than 70 years old and of coronary artery disease and in patients undergoing mitral valve replacement there was a higher incidence of functional class IV. The operative mortality rate was 2.3% (3 of 127 patients). No patient failed to be discontinued from cardiopulmonary bypass and all three deaths occurred after mitral valve replacement, with one from complications of chronic renal failure and dialysis. There was no significant difference in patients who either did or did not have a concomitant coronary artery bypass graft and there was no difference related to age or functional class. Postoperative complications occurred in five patients in the valve repair group, including recurrent mitral regurgitation in two necessitating reoperation, and in three patients in the valve replacement group. With newer operative and postoperative management techniques, especially preservation of the papillary muscle annular continuity, the risk of mitral valve surgery, particularly of valve repair, is considerably lower than in previous years. PMID- 2254542 TI - Apical segmental dysfunction in hypertrophic cardiomyopathy: subgroup with unique clinical features. AB - A segmental wall motion abnormality is an unusual finding in patients with hypertrophic cardiomyopathy. To clarify its clinical significance, 48 patients with hypertrophic cardiomyopathy were analyzed. Eight patients (Group A) had apical segmental dysfunction; 40 (Group B) had normal wall motion. No patient in either group had coronary artery stenosis on selective coronary arteriography. In all patients in Group A, apical segmental dysfunction was revealed by left ventriculography; however, it could be detected by echocardiography in only two patients in Group A. Left ventricular hypertrophy by electrocardiogram (ECG) was more common in Group B (p less than 0.05). Abnormal Q waves were more frequently discovered in Group A (p less than 0.005) and were recognized predominantly in the lateral leads. On serial ECGs, a gradual development of abnormal Q waves was noted in six of eight patients in Group A. Malignant arrhythmias were more common in Group A (p less than 0.001). In two patients in Group A, left ventricular dilation and congestive heart failure developed during the follow-up period. Thus, the presence of a Q wave in the lateral leads on an ECG in patients with hypertrophic cardiomyopathy may indicate the presence of apical segmental dysfunction. Left ventriculography should be performed to examine the presence of this abnormality and 24 h ambulatory ECG monitoring should be done to detect malignant arrhythmias in patients who have abnormal Q waves in the lateral leads. Patients with this unique type of hypertrophic cardiomyopathy need careful follow up evaluation. PMID- 2254543 TI - Contrast echocardiographic mapping of collateralized myocardium in humans before and after coronary angioplasty. AB - Conventional coronary arteriography is able to demonstrate the presence of coronary collateral vessels but cannot delineate the specific region of myocardium to which they supply blood. To test the hypothesis that contrast echocardiography can specifically identify collateralized myocardium, contrast echocardiographic perfusion "maps" were compared in patients with (n = 12) and without (n = 12) angiographic evidence of coronary collateral flow, both before and after coronary angioplasty. Contrast echocardiographic images of the mid-left ventricle in the short-axis view at end-diastole were obtained after separate injections of a sonicated contrast agent into both the right and the left coronary arteries. A computer-based contouring system was used to determine the individual areas of myocardium perfused by each of the two coronary arteries and then to superimpose the images of the two perfusion beds. The resulting area of overlapping perfusion represented myocardium receiving blood flow from both coronary systems and was defined as collateralized myocardium. To normalize for heart size, overlap area was expressed as a percent of total myocardial area, which was the area between endocardium and epicardium in the short-axis view. To adjust for differences in vascular distribution, overlap area was expressed as a percent of the perfusion area of the recipient vessel. In patients with angiographic collateral flow, the recipient vessel was that vessel receiving the collateral flow. In patients without angiographic collateral flow, the right coronary artery was considered the recipient vessel. Overlap area was 1.3 +/- 0.4% of total myocardial area and 6.6 +/- 1.7% of recipient vessel area in patients without angiographic evidence of collateral flow compared with 30.6 +/- 2.5% and 89.2 +/- 6.4%, respectively, in patients with angiographic collateral flow (p less than 0.001 for both). In four patients in whom angiographic collateral flow was abolished by angioplasty, overlap area decreased from 30.3 +/ 5.3% to 6.8 +/- 2.7% of total myocardial area and from 100% to 18.5 +/- 5.4% of recipient vessel area (p less than 0.05 for both). Thus, contrast echocardiography is able to map the specific myocardial territory perfused by coronary collateral flow and document an immediate reduction in perfusion in this territory when collateral flow is abolished by angioplasty. PMID- 2254544 TI - Contrast echocardiography and coronary collateral flow. PMID- 2254545 TI - Intravenous contrast echocardiography with use of sonicated albumin in humans: systolic disappearance of left ventricular contrast after transpulmonary transmission. AB - The transmission of echocardiographic contrast medium and the cyclic changes in left ventricular videodensity during transpulmonary contrast echocardiography were investigated in nine adult volunteers with the use of intravenous injections of sonicated albumin (microbubble size 5.2 +/- 2.6 microns). Right and left ventricular and myocardial contrast were quantitated by videodensitometric analysis. The injections caused no symptoms, and no hemodynamic or electrocardiographic changes were observed. All injections resulted in right ventricular contrast. Mean peak right ventricular videodensity was 75 +/- 48 at end-diastole and 61 +/- 36 gray scale U/pixel at end-systole (p less than 0.05). Seventy-eight percent of injections resulted in left ventricular contrast with a mean peak videodensity of 21 +/- 33 gray scale U/pixel. Early systole was associated with a rapid decrease in left ventricular contrast intensity with near total disappearance of contrast by end-systole (from 23 +/- 33 and 17 +/- 23 U/pixel at end-diastole to 6 +/- 10 and 3 +/- 2 at end-systole at the left ventricular base and apex, respectively; p less than 0.05). None of the injections resulted in myocardial contrast enhancement by visual or quantitative analysis. Thus, left ventricular contrast echocardiography can be achieved after intravenous injections of sonicated albumin. Transpulmonary left ventricular contrast echocardiography is associated with near total disappearance of contrast during systole. This may be secondary to the destruction of microbubbles by the high left ventricular systolic pressure. These findings may help explain the limited success of this technique thus far for myocardial perfusion imaging. PMID- 2254546 TI - Ventricular stroke work loss: validation of a method of quantifying the severity of aortic stenosis and derivation of an orifice formula. AB - Because aortic stenosis results in the loss of left ventricular stroke work (due to resistance to flow through the valve and turbulence in the aorta), the percentage of stroke work that is lost may reflect the severity of stenosis. This index can be calculated from pressure data alone. The relation between percent stroke work loss and anatomic aortic valve orifice area (measured by planimetry from videotape) was investigated in a pulsatile flow model. Thirteen valves were studied (nine human aortic valves obtained at necropsy and four bioprosthetic valves) at stroke volumes of 40 to 100 ml, giving 57 data points. Valve area ranged from 0.3 to 2.8 cm2 and mean systolic pressure gradient from 3 to 84 mm Hg. Percent stroke work loss, calculated as mean systolic pressure gradient divided by mean ventricular systolic pressure x 100%, ranged from 7 to 68%. It was closely related to anatomic orifice area with an inverse exponential relation and was not significantly related to flow (r = -0.15). An orifice formula was derived that predicted anatomic orifice area with a 95% confidence interval of +/ 0.5 cm2 (orifice area [cm2] = 4.82 [2.39 x log percent stroke work loss], r = 0.94, SEE = 0.029). These results support the clinical use of percent stroke work loss as an easily obtained index of the severity of aortic stenosis. PMID- 2254547 TI - Evaluating severity of aortic stenosis: new validation of an old method. PMID- 2254548 TI - Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: a Doppler echocardiographic study. AB - Patients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension. The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 +/- 0.11 versus 0.32 +/- 0.09; p less than 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 +/- 2.2 versus 8.6 +/- 1.2 cm2/m2; p less than 0.005). Acting as a receiving chamber, the left ventricle was maximally compressed by the volume overloaded right ventricle in late diastole, coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 +/- 0.14 versus 1.03 +/- 0.1; p less than 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling. PMID- 2254549 TI - Demonstration of an area of slow conduction in human atrial flutter. AB - Ten patients with chronic atrial flutter were studied prospectively using electrophysiologic mapping and pacing techniques to assess the mechanism of atrial flutter and the presence of an area of slow conduction in the atria. Electrograms recorded from greater than or equal to 30 right atrial sites for each patient during atrial flutter demonstrated that right atrial free wall activation was craniocaudal and that the interatrial septum activation was caudocranial, consistent with a reentrant circuit involving the right atrium. In six patients, slow conduction occurred during atrial flutter in the inferior right atrium and was spatially associated with fractionated electrographic recordings. In the other four patients, a "missing" interval of electrical activity occurred in the inferior right atrium for an average of 40% of the atrial flutter cycle. Transient entrainment criteria were demonstrated in each patient during rapid high right atrial pacing. The mean activation time from the high right atrial pacing site to the coronary sinus (inferior left atrial) recording site was long (228 ms) and consistent with activation through an area of slow conduction. During rapid pacing of atrial flutter from the coronary sinus site, no transient entrainment criteria could be demonstrated. The mean activation time from the coronary sinus pacing site to the high right atrial recording site was relatively short (134 ms) and consistent with orthodromic activation of the high right atrium not through an area of slow conduction. High right atrial pacing during sinus rhythm at rates similar to atrial flutter demonstrated a short activation time to the coronary sinus and low right atrial sites (mean 169 and 88 ms, respectively), indicating activation that did not traverse an area of slow conduction. Coronary sinus pacing during sinus rhythm demonstrated the same phenomena. Low right atrial electrograms recorded during sinus rhythm and during rapid pacing of sinus rhythm were not fractionated, although they were during atrial flutter. Thus, atrial mapping and pacing data were complementary, indicating that human atrial flutter in the patients studied was generated by a reentrant circuit in the right atrium, with an area of slow conduction in the low right atrium present only during atrial flutter. PMID- 2254550 TI - Noninvasive detection of patients with ischemic and nonischemic heart disease prone to ventricular fibrillation. AB - Abnormalities in the fast Fourier transforms of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm appear to distinguish patients with ischemic heart disease and sustained monomorphic ventricular tachycardia from those without ventricular tachycardia. This study was performed to determine the power of frequency analysis to detect patients with a history of ventricular fibrillation, to determine the extent to which spectra of signal averaged ECGs from patients with ischemic and nonischemic heart disease are comparable and to compare results of signal-averaged ECG analysis in patients with ventricular fibrillation with results of programmed ventricular stimulation. Signal-averaged ECGs were obtained during sinus rhythm from 60 patients with sustained ventricular tachycardia (Group I) and 34 patients with ventricular fibrillation (Group II). Results of signal-averaged ECG analysis were abnormal in 92% of patients with ventricular tachycardia and 85% of patients with ventricular fibrillation (p = NS). Abnormal spectra were detected in the signal-averaged ECGs from 90% of patients with ischemic and from 86% of patients with nonischemic heart disease (p = NS). In contrast, the results of programmed stimulation differed markedly between the two patient groups. Sustained ventricular arrhythmias were induced in 91% of the patients with ventricular tachycardia compared with only 46% of those with ventricular fibrillation (p less than 0.0001). Moreover, ventricular tachycardia was inducible in 81% of patients with ischemic heart disease compared with only 50% of those with nonischemic heart disease (p less than 0.02). Thus, abnormalities in the spectra of signal-averaged ECGs were found in the majority of patients with ventricular fibrillation and were detectable even in those whose arrhythmia was not inducible by programmed stimulation. These results broaden the potential clinical application of noninvasive interrogation of signal-averaged ECGs to include the prospective identification of patients with ischemic or nonischemic heart disease prone to ventricular tachycardia or ventricular fibrillation. PMID- 2254551 TI - Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection. AB - Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions. PMID- 2254552 TI - Assessment of ventricular septal defect closure by intraoperative epicardial ultrasound. AB - Intraoperative epicardial two-dimensional echocardiographic imaging, color flow mapping and contrast echocardiography were used in 31 patients after patch closure of a ventricular septal defect to determine their respective values in the assessment of residual shunting after cardiopulmonary bypass and for the prediction of long-term results. Epicardial imaging showed no incidence of patch dehiscence. Residual shunting detected by color flow mapping or contrast echocardiography was graded into one of four categories (0 to III). Real time analysis of color flow mapping studies suggested no shunting (grade 0) in 2 patients, grade I shunting in 20, grade II in 8 and grade III in 1; contrast studies suggested grade 0 in 15, grade I in 6, grade II in 8 and grade III in 2. Interobserver variation in real time encoding of grade I or II shunting was 25% by color flow mapping and 6% by contrast echocardiography. Subsequent frame by frame analysis revealed that both diastolic and early systolic right ventricular turbulence gave rise to false positive results during real time analysis of color flow mapping studies. Color flow mapping allowed exact localization of residual shunting, whereas contrast echocardiography allowed better semiquantification. Postbypass results were correlated in 30 patients with late postoperative precordial studies (mean interval 7.5 months). Persistent shunts were found in 6 (20%) of 30 patients. No patient required reoperation for residual shunting. The predictive value of immediate grade I or II shunting as a marker for persistent long-term shunting was poor, whereas both patients with immediate grade III shunting had shunt persistence, indicating that immediate revision should be considered in such patients. Intraoperative epicardial ultrasound is valuable for the immediate exclusion of important residual shunting after ventricular septal defect closure. Maximal information is obtained when color flow mapping and contrast echocardiography are used in combination. PMID- 2254553 TI - Prevalence of additional cardiovascular anomalies in patients referred for transcatheter closure of patent ductus arteriosus. AB - Catheter closure of the patent ductus arteriosus is now a reality. The purpose of this study was to establish the prevalence of associated cardiovascular defects and the accuracy of echocardiography in patients referred for transvenous ductal closure. This study reviewed 146 patients seen from 1981 to 1988: 126 with only a patent ductus arteriosus (Group I) and 20 with additional cardiovascular anomalies (Group II). Groups I and II did not differ significantly in age, gender or physical examination except for the presence of a continuous murmur (Group I 100% versus Group II 80%, p less than 0.001). A left patent ductus arteriosus was visualized by two-dimensional echocardiography in 96% of patients and was evident by Doppler study in 100%. A patent ductus arteriosus was not seen in six patients including a patient who was found to have only a collateral network from the aorta to the main pulmonary artery. The 12 patients with noncardiovascular abnormalities such as Down's syndrome were more likely than the overall group to have additional cardiovascular anomalies (6 of 12, p = 0.001). The cardiovascular anomalies encountered were varied. Eight of the 20 patients with such anomalies had only a restrictive ventricular septal defect in addition to the patent ductus arteriosus. Significant anomalies found at catheterization included two thoracic arteriovenous malformations and an isolated right carotid artery draining into the right pulmonary artery by way of a right ductus arteriosus. This study indicates that echocardiography is an effective diagnostic technique in this patient group. A thorough cardiac catheterization with angiography should be performed before implantation of a ductal device. PMID- 2254554 TI - Intraoperative echocardiography in infants and children with congenital cardiac shunt lesions: transesophageal versus epicardial echocardiography. AB - To determine the utility and limitations of intraoperative transesophageal echocardiography in infants and children with congenital intracardiac shunts, intraoperative transesophageal (n = 50) and epicardial (n = 49) echocardiograms were performed before and after cardiopulmonary bypass in children from 4 days to 16 years old and 3 to 45 kg in body weight. A miniaturized transesophageal probe (6.9 mm maximal diameter) was used in 36 patients weighting less than or equal to 20 kg. Epicardial imaging was performed with a 5 MHz precordial probe. The intraoperative transesophageal echocardiographic findings before and after cardiopulmonary bypass were correct and complete in 94% of patients. Transesophageal echocardiography correctly identified atrial septal defects, most types of ventricular septal defects, anomalous pulmonary veins, atrioventricular septal defects, tetralogy of Fallot, truncus arteriosus and double inlet ventricles. It failed to provide a correct diagnosis in only three patients, all of whom had doubly committed subarterial ventricular septal defects. Epicardial echocardiography identified all cases that had a doubly committed subarterial ventricular septal defect. A correct and complete intraoperative diagnosis was obtained with the use of epicardial imaging in 92% before and after cardiopulmonary bypass, but this technique required interruption of surgery and could not be completed in three patients because of induced arrhythmias and hypotension. These results demonstrated that intraoperative transesophageal echocardiography consistently defined important morphologic, color and pulsed Doppler ultrasound features of most congenital shunt lesions. Lesions that involved the right ventricular outflow tract are sometimes difficult to image with uniplane transesophageal echocardiography. There were no complications in any of the 50 subjects. PMID- 2254555 TI - Increased birth prevalence of cardiac defects in Yuma, Arizona. AB - A systematic study was undertaken to estimate the birth prevalence of congenital heart disease because there was a clinical impression that a disproportionate number of cases occurred in Yuma, Arizona. Control data were obtained from Sierra Vista, Arizona, a region with similar demographic characteristics, and from the Baltimore-Washington Infant Study. Patients with chromosomal or syndromal associations were excluded. In the Baltimore-Washington Infant Study only echocardiographic and invasively documented cases were included. From 1983 to 1988 the birth prevalence was significantly higher in Yuma (10.5/1,000) than in Sierra Vista (5.4/1,000, p less than 0.0001). As assessed only by invasive or echocardiographic diagnosis, there was a higher birth prevalence of congenital heart disease in the study population (6.7/1,000) compared with both the Baltimore-Washington Infant Study (3.7/1,000, p = 0.0008) and Sierra Vista (4.6/1,000, p = 0.04). Families were interviewed to exclude cases in which the mother did not spend the month before conception and the first trimester in Yuma or Sierra Vista. The birth prevalence for Yuma (6.0/1,000) remained significantly greater than that for Sierra Vista (3.8/1,000, p = 0.03). The exclusion of cases in which the mother resided elsewhere suggests, but does not prove, that an environmental influence may have played a role in the increased birth prevalence of congenital heart disease in this community. PMID- 2254556 TI - On the birth prevalence of congenital heart disease. PMID- 2254557 TI - Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution. AB - The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy. PMID- 2254558 TI - Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS) AB - In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity, the effects of prophylactic antiarrhythmic treatment were investigated prospectively in patients with persisting asymptomatic complex arrhythmias after myocardial infarction. End points were total mortality and arrhythmic events (sudden death, sustained ventricular tachycardia and ventricular fibrillation). Of 1,220 consecutively screened survivors of myocardial infarction, 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study. They were randomized to individualized antiarrhythmic treatment (Group 1, n = 100), treatment with low dose amiodarone, 200 mg/day (Group 2, n = 98) or no antiarrhythmic therapy (Group 3 [control group], n = 114). During the 1 year follow-up period, 10 patients in Group 1 died, as did 5 in Group 2 and 15 in Group 3. On the basis of an intention to treat analysis, the probability of survival of patients given amiodarone was significantly greater than that of control patients (p less than 0.05). In addition, arrhythmic events were significantly reduced by amiodarone (p less than 0.01). These effects were less marked and not significant for individually treated patients (Group 1). These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infarction in patients at high risk of sudden death. PMID- 2254559 TI - Antiarrhythmic treatment and myocardial infarction. PMID- 2254560 TI - Effects of nicardipine, a calcium antagonist, on myocardial salvage and high energy phosphate stores in reperfused myocardial injury. AB - The current study determined the effectiveness of nicardipine, a 1,4 dihydropyridine calcium antagonist, in preserving reperfused myocardium in a cat model of temporary coronary occlusion and ascertained if replenishment of myocardial phosphate stores during reperfusion as defined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was indicative of salvage. Twenty open chest, anesthetized cats were studied with use of a snare ligature around the proximal left anterior descending coronary artery, with a coil sutured to the epicardial surface overlying the distribution of the artery. Peak areas of phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP) NMR signals were measured during 1 h of occlusion followed by 1.5 h of reperfusion. Infarct size and jeopardy area were determined in vitro by simultaneous infusion of phthalocyanine blue dye and triphenyltetrazolium chloride into the aorta and the left anterior descending coronary artery, respectively, after 5 h of myocardial reperfusion. Nicardipine-treated and control groups had similar jeopardy area values (41.2 +/- 1.6% versus 47.4 +/- 3.1% of the left ventricle), but infarct area was significantly reduced in the nicardipine-treated group (3.2 +/- 1.1% versus 24.9 +/- 7.5% of jeopardy area, p less than 0.01). High energy phosphate compounds remained markedly altered during reperfusion in both groups. No significant improvement in phosphocreatine or inorganic phosphate recovery was observed in animals pretreated with nicardipine despite an 87% reduction in infarct size. Myocardial ATP was greater during reperfusion in the nicardipine treated compared with the control group (average over initial 90 min of reperfusion 58 +/- 6% versus 46 +/- 3% of baseline values, p less than 0.05), suggesting improved recovery of ATP. However, the measured levels of high energy phosphate compounds during reperfusion and their ratios did not correlate with infarct size and thus were not predictive of myocardial salvage. PMID- 2254561 TI - Hemodynamic efficacy of rapid saline infusion and dobutamine versus saline infusion alone in a model of cardiac rupture. AB - Despite recent reports describing survival after cardiac rupture, the effectiveness of circulatory support while awaiting definitive surgical treatment is controversial. To assess the efficacy of volume expansion and pharmacologic support in cardiac tamponade due to cardiac rupture, a model of hemorrhagic cardiac tamponade was developed and treatment with rapid saline infusion and dobutamine was compared with rapid saline infusion alone in 15 closed chest dogs. A right ventricular wound of reproducible size was produced by deflating an aortic valvuloplasty balloon that had previously been passed by way of the internal jugular vein into the pericardial space and through a stab wound in the right ventricular free wall. Hemodynamic values were compared at baseline, during tamponade and after a rapid infusion (1 liter at 100 ml/min) of either saline solution alone or saline solution plus dobutamine (20 micrograms/kg per min). Atrial and pericardial pressures increased significantly in both groups. Mean arterial pressure, cardiac output and stroke volume increased with combined saline and dobutamine infusion to values similar to those at baseline (91 +/- 19%, 114 +/- 43% and 94 +/- 37% of baseline, respectively). In contrast, saline infusion alone caused a small increase in cardiac output but failed to significantly increase mean arterial pressure or stroke volume (76.8 +/- 14.2%, 55 +/- 18% and 51 +/- 17% of baseline, respectively). Combined rapid infusion of saline solution and dobutamine infusion has a more beneficial hemodynamic effect and may be more effective than rapid saline infusion alone in resuscitating patients with hemorrhagic cardiac tamponade due to cardiac rupture. PMID- 2254562 TI - Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet activating factor antagonist. AB - To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation. PMID- 2254563 TI - Effects of dipyridamole and aminophylline on hemodynamics, regional myocardial blood flow and thallium-201 washout in the setting of a critical coronary stenosis. AB - Experiments were performed to characterize the interaction of intravenous dipyridamole and aminophylline on thallium-201 transport kinetics, regional myocardial blood flow and systemic hemodynamics in the presence of a critical coronary artery stenosis. In 12 dogs with a critical left anterior descending coronary artery stenosis, arterial pressure decreased from a mean value (+/- SEM) of 107 +/- 6 to 94 +/- 3 mm Hg (p less than 0.05) and distal left anterior descending artery pressure decreased from 70 +/- 7 to 55 +/- 4 mm Hg (p less than 0.05) after intravenous administration of dipyridamole (0.25 mg/kg body weight). In the left anterior descending perfusion zone, the endocardial/epicardial flow ratio decreased from 0.70 to 0.36 and the intrinsic thallium washout rate was significantly prolonged. Intravenous aminophylline (5 mg/kg) reversed the dipyridamole-induced systemic hypotension and transmural coronary steal and restored the thallium washout rate to baseline values. In six other dogs, aminophylline alone resulted in no alterations in systemic and coronary hemodynamics or regional myocardial blood flow. As expected, dipyridamole-induced vasodilation and coronary steal were prevented by aminophylline pretreatment. These data show that in a canine model of partial coronary stenosis, systemic hypotension, adverse regional flow effects (coronary steal) and prolonged thallium-201 washout consequent to intravenously administered dipyridamole are promptly reversed by intravenous aminophylline administration. Aminophylline alone had no significant hemodynamic and coronary flow effects. This study provides further insight into the altered thallium kinetics occurring as a consequence of dipyridamole-induced vasodilation and suggests that the prompt reversal of symptoms and signs of ischemia with aminophylline in patients receiving intravenous dipyridamole for clinical imaging studies probably reflects the reversal of transmural coronary steal. PMID- 2254564 TI - The president's mailbag. PMID- 2254565 TI - Evidence for decreased transport of PNMT protein in advanced Alzheimer's disease. AB - Phenylethanolamine N-methyltransferase (PNMT) is the rate-limiting enzyme in the synthesis of epinephrine and a specific marker for adrenergic neurons. PNMT protein is decreased in axon terminals in brains from patients with Alzheimer's disease due to retrograde degeneration of epinephrine neurons. To determine the subcellular mechanism underlying retrograde degeneration, the distribution of PNMT between axon terminal and cell body was calculated in early and advanced Alzheimer cases compared with age-matched controls. In early Alzheimer's disease there is a decrease in PNMT in axon terminals and in total PNMT in epinephrine cell bodies and terminals compared with control values. There is no difference in the ratio of PNMT in cell body/axon terminal compared with controls. In contrast, in advanced Alzheimer's disease, PNMT activity increases by 124% in epinephrine neuronal cell bodies compared with controls. Immunochemical titration shows that this increased enzyme activity is due to an increase in PNMT protein. The cell body/axon terminal ratio of PNMT is increased 2.5-fold in advanced Alzheimer's disease compared with controls. These findings are consistent with the hypothesis that in early Alzheimer's disease there is a decreased synthesis or increased degradation of PNMT. However, in advanced Alzheimer's disease we propose that the accumulation of this enzyme in the perikarya results from a diminished transport of PNMT to axon terminals. We further postulate that epinephrine, the product of PNMT, and its further metabolites are endogenous neurotoxins. Therefore, the accumulation of PNMT in epinephrine cell bodies may contribute to the degeneration of these neurons in Alzheimer's disease. PMID- 2254566 TI - Reduced beta-cell secretion and insulin hepatic extraction in healthy elderly subjects. AB - One factor responsible for the altered carbohydrate metabolism in elderly subjects is impaired insulin release; however, difficulties in directly measuring insulin secretion have limited studies on pancreatic activity and on the contribution of the liver to insulin delivery. This study investigated beta-cell performance and insulin hepatic extraction under dynamic conditions in normal elderly subjects. Two strictly comparable groups of 12 young controls (Y, 27 +/- 1 (SE) years, 73 +/- 3 kg) and 12 elderly men (E, 69 +/- 2 years, 73 +/- 3 kg) were chosen on the basis of normal OGTT and normal insulin sensitivity in order to investigate a "pure" age effect. The subjects underwent a 4-hour frequently sampled intravenous glucose tolerance test (FSIGT) (dose 0.3 g/kg). Although no significant differences were found between the fasting levels of glucose and insulin (respectively: E: 89 +/- 3 mg/dL versus Y: 87 +/- 2, P greater than .1; and E: 5.0 +/- 0.5 microU/mL versus Y: 6.8 +/- 1.0, P greater than .05), basal C peptide was found to be lower in the old subjects: 0.43 +/- 0.06 ng/mL versus 0.70 +/- 0.11 (P less than .025). The patterns of glucose and insulin during the FSIGT were similar, whereas C-peptide concentration in E was systematically lower, suggesting a reduced insulin secretion. To verify this hypothesis, we analyzed FSIGT data with a mathematical model-based method that provides a noninvasive direct measurement of the time courses of insulin secretion and hepatic extraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254567 TI - Early readmission of elderly patients with congestive heart failure. AB - Repetitive hospitalizations are a major health problem in elderly patients with chronic disease, accounting for up to one fourth of all inpatient Medicare expenditures. Congestive heart failure, one of the most common indications for hospitalization in the elderly, is also associated with a high incidence of early rehospitalization, but variables identifying patients at increased risk and an analysis of potentially remediable factors contributing to readmission have not previously been reported. We prospectively evaluated 161 patients 70 years or older that had been hospitalized with documented congestive heart failure. Hospital mortality was 13% (n = 21). Among patients discharged alive, 66 (47%) were readmitted within 90 days. Recurrent heart failure was the most common cause for readmission, occurring in 38 patients (57%). Other cardiac disorders accounted for five readmissions (8%), and noncardiac illness led to readmission in 21 cases (32%). Factors predictive of an increased probability of readmission included a prior history of heart failure, four or more admissions within the preceding 8 years, and heart failure precipitated by an acute myocardial infarction or uncontrolled hypertension (all P less than .05). Using subjective criteria, 25 first readmissions (38%) were judged possibly preventable, and 10 (15%) were judged probably preventable. Factors contributing to preventable readmissions included noncompliance with medications (15%) or diet (18%), inadequate discharge planning (15%) or follow-up (20%), failed social support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%). Thus, early rehospitalization in elderly patients with congestive heart failure may be preventable in up to 50% of cases, identification of high risk patients is possible shortly after admission, and further study of nonpharmacologic interventions designed to reduce readmission frequency is justified. PMID- 2254568 TI - Prediction of independent functioning and behavior problems in geriatric patients. AB - Folstein's Mini Mental State Exam, a test assessing the capacity to perform novel and/or repetitive motor tasks (Behavioral Dyscontrol Scale) and a brief measure of working memory were used in a sample of 50 male Veterans Affairs geriatric clinic patients who ranged in age from 63 to 105 (mean, 80.1). The purpose of this study was to attempt to predict the patients' capacity to regulate their behavior independently. We hypothesized that frontal lobe disorders often impair a patient's ability to function autonomously and that the Behavioral Dyscontrol Scale, a measure of frontal lobe impairment, would best predict the capacity for independent regulation of purposeful behavior. Therefore, we examined the relationship of the Behavioral Dyscontrol Scale with spouses' and caregivers' ratings of patients' independent living skills, and with behaviors that interfere with independent functioning. The results of hierarchial regression analyses indicated that the Behavioral Dyscontrol Scale was the only predictor of functional autonomy and was the best predictor of both impulsivity and apathy among geriatric patients. The Behavioral Dyscontrol Scale appears to assess a different functional domain than do the MMSE and similar measures, which rely heavily on the evaluation of orientation and gross cognitive status. PMID- 2254569 TI - The nursing home life-space diameter. A measure of extent and frequency of mobility among nursing home residents. AB - We developed the Nursing Home Life-Space Diameter (NHLSD) as a measure of the extent and frequency of mobility among skilled nursing facility (SNF) residents. Intrarater and interrater reliability was assessed in a small sample of SNF residents. The means and ranges of NHLSD scores, the characteristics associated with NHLSD score, and the association between NHLSD score and other functional characteristics were then determined among 398 residents of 12 SNFs. NHLSD scores ranged from 0, signifying bed- or chair-bound to 50, signifying leaving the facility daily. The correlation between NHLSD scores by two nurses was 0.951; the correlation between scores at two points of time was 0.922. Mean score among the 398 subjects was 27.05. Decreased vision, presence of a neurologic disease, and arthritis were all associated with lower NHLSD score. Mobility (NHLSD) score was moderately correlated with other functional characteristics such as participation in social activities (Spearman's correlation = +0.565). The NHLSD, which represents a simple and reliable assessment of mobility among SNF residents, could be used to assess the effect of interventions and to monitor changes among SNF residents. PMID- 2254570 TI - Beliefs and policies of Maryland nursing home medical directors regarding tetanus immunization. AB - Tetanus is more common in the elderly, who have a higher case-fatality rate than younger age groups. Immunization against tetanus is recommended for all elderly, including nursing home residents, but the tetanus immunization policies of nursing homes are unknown. Nursing home medical directors in Maryland were surveyed about their beliefs concerning tetanus and the tetanus immunization policies of their nursing homes. One hundred twenty-five directors of 212 responded (59%). In most of the nursing homes, no policies existed for routine tetanus immunization. Medical directors graduating from medical school after 1960 and medical directors with more than 50 nursing home patients were more likely to believe that tetanus immunization is cost-effective in nursing home patients. Only 3% of the respondents always immunize their nursing home patients with chronic skin ulcers. We believe tetanus immunization is an uncommon practice in Maryland nursing homes. Nursing home medical directors should establish policies to promote tetanus immunization. PMID- 2254571 TI - Multiple stumbles: a risk factor for falls in community-dwelling elderly. A prospective study. AB - To better understand risk factors for falls among community-dwelling elderly, we analyzed data from a sample of elderly Medicare beneficiaries interviewed in 1987 and a year later. Demographic, social, medical, and functional information were obtained by telephone interviews with 736 subjects (68% women) whose average age was 76.5 (range, 65-99). At baseline, 63 subjects reported a fall and 67 reported two or more stumbles without a fall in the past month. At the second interview follow-up information on falls in the past year was obtained on 586 subjects. One hundred twenty-seven (22%) subjects reported one or more falls. Baseline risk factors that were independent predictors of a fall at the second interview included two or more stumbles (adjusted odds ratio [AOR] 2.3, 95% confidence interval [CI], 1.2-4.5), one or more falls (AOR 5.9, 95% CI 2.9-12.2), having spent 4 or more days in bed in the past month (AOR 7.7, 95% CI 1.9-31.0), and self-reported declining health status (AOR 2.0, 95% CI 1.1-3.5). Falls and stumbles are prevalent among community-dwelling elderly. After controlling for covariates, we found subjects who reported two or more stumbles in the past month are at increased risk for a fall in the following year. PMID- 2254572 TI - Injuries in an elderly inner-city population. AB - Even though injuries are a leading cause of morbidity and mortality among the elderly in the United States, no comprehensive population-based study of nonfatal and fatal injuries has been carried out in an elderly minority inner-city population. To study injuries in this population, we developed an active surveillance system as part of a large injury prevention program in a poor urban black community. We report 577 cases of nonfatal and fatal injuries in a community of 12,139 persons 65 years of age and older that resulted in emergency room treatment or death between March 1, 1987, and February 29, 1988. Nearly 5% of the elderly population was treated at an emergency room for, or died as a result of, an injury during the study period; the overall injury rate was 48 injuries per 1,000 persons. Injury rates for older women exceeded those for older men and increased with advancing age in both sexes. Fall injuries accounted for 312 (54%) of all injuries and 75% of all hospitalizations for injury. Motor vehicle incidents and violence were the second and third most common injuries, accounting for 13% and 7% of injuries, respectively. Given the predominance of falls relative to other injuries, prevention of falls should receive major emphasis in injury prevention efforts in inner-city minority populations. PMID- 2254573 TI - Causes of death in the elderly and their changing pattern in Hisayama, a Japanese community. Results from a long-term and autopsy-based study. AB - The causes of death for the elderly were prospectively studied in Hisayama, Japan, a rural community. We compared 1,621 subjects, aged 40 years or over, recruited in 1961, and 2,053 subjects recruited in 1974. Each cohort was studied in a follow-up that lasted 10 years; they had autopsy rates of 82.1% and 86.1% during each 10-year period, respectively. The most common causes of death for those aged 70 years or over were cerebrovascular disease, malignant neoplasms, and pneumonia. Deaths due to cerebrovascular disease tended to decrease in the recent cohort, but the proportion of decline was more prominent in cases aged 40 to 69 years. There was a sex difference in the changing pattern of mortality from heart diseases including ischemic heart disease. Deaths by both heart diseases and ischemic heart disease increased in the more recent cohort of aged women, whereas they decreased in the aged men. Pneumonia was an important cause of death for the elderly in both cohorts. Deaths due to "senility" were rare, being only 1% of the deceased aged 70 or over. With prolonged lifespan, especially for women, the impact of atherosclerosis and its related disorders on the recent Japanese aged population appears to have increased. PMID- 2254574 TI - The aging hip. St. Louis University Geriatric Grand Rounds. PMID- 2254575 TI - Antimicrobial therapy for the elderly patient. PMID- 2254576 TI - The new geriatrics. PMID- 2254577 TI - Geriatric depression scale. PMID- 2254578 TI - Permanent pacemakers and dementia. PMID- 2254579 TI - Phenothiazines in dementia. PMID- 2254580 TI - Screaming in the nursing home. PMID- 2254581 TI - The role of iron in t-butyl hydroperoxide-induced lipid peroxidation and hepatotoxicity in rats. AB - Treatment of rats with 100 mg kg-1 t-butyl hydroperoxide led to an enhanced ethane exhalation as a marker of in vivo lipid peroxidation, as well as a moderate hepatoxicity as evidenced by a rise in plasma activities of liver specific enzymes (glutamate-pyruvate transaminase and sorbitol dehydrogenase) and an increase in hepatic calcium content. Furthermore, a depletion of hepatic glutathione by 17% was observed. Apart from the loss of glutathione, all these effects were antagonized by pretreatment of rats with the potent iron chelator deferrioxamine and potentiated by pretreatment with low concentrations of FeSO4 having no pro-oxidant activity per se; this was also the case in rats under conditions of iron overload (experimental haemochromatosis). These data indicate a close relationship between t-butyl hydroperoxide-induced lipid peroxidation and its hepatotoxicity, and point out the importance of iron in catalysing reinitiation (propagation) reactions of lipid peroxidation in vivo. PMID- 2254582 TI - The role of iron and glutathione in t-butyl hydroperoxide-induced damage towards isolated perfused rat livers. AB - The hepatotoxic and lipid peroxidative potentials of t-butyl hydroperoxide (t BuOOH) towards isolated perfused rat livers were investigated at doses of 1 and 3 mmol l-1. t-BuOOH led to a concentration-dependent release of cytosolic (glutamate-pyruvate transaminase and lactate dehydrogenase) and mitochondrial (glutamate dehydrogenase) enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an enhanced formation and release of malondialdehyde (MDA) by the liver. These effects were blocked in the presence of the potent iron chelator deferrioxamine, and enhanced in livers from iron-overloaded as well as in livers from glutathione-depleted rats. Our results indicate that the hepatotoxic and pro-oxidant actions of organic hydroperoxides depend upon the presence of ionized iron as a catalyst of radical-forming breakdown reactions, and are potentiated by impairment of glutathione-dependent detoxification reactions. PMID- 2254583 TI - Prevention of hydrolysable tannin toxicity in goats fed Clidemia hirta by calcium hydroxide supplementation. AB - Although plants containing hydrolysable tannins can be hepatotoxic, such poisoning has not been reported in Indonesia despite the presence of these plants. In order to determine the hepatotoxic potential of Indonesian plants, goats were intoxicated experimentally with the Indonesian plant Climedia hirta (harendong), which contained 19% hydrolysable tannin. The prophylactic effect of Ca(OH)2 supplementation on the disease was also examined. Two groups of goats were fed for 28 days with grain-based pellets containing 50% harendong leaf or 50% harendong leaf + 8% Ca(OH)2. Two control groups were fed similar pellets containing 50% of the non-toxic elephant grass (Pennisetum purpureum) with and without 8% Ca(OH)2. Serum enzymes indicative of liver damage were monitored during the experiment and histopathological examination of selected tissues was done at the conclusion of the experiment. In goats given unsupplemented harendong pellets there was a significant increase in aspartate aminotransferase and glutamate dehydrogenase from 50.2 and 20.6 U l-1 to 219.6 and 63.3 U l-1, respectively. These changes were associated with moderate to severe nuclear plemorphism, vacuolation and megalocytosis of hepatocytes and deposits of brown pigment in the Kupffer cells. There was also nephrosis of the renal convoluted tubules and collecting ducts, abomasitis and enteritis. Biochemical and histological changes were reduced significantly in the harendong + Ca(OH)2 group and virtually absent from control groups. It is concluded that hydrolysable tannins in harendong leaf are hepato- and nephrotoxic and associated with gastroenteritis, but that poisoning may be ameliorated by Ca(OH)2 supplementation. PMID- 2254584 TI - Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF). AB - The reproductive effect of N,N-dimethylformamide (DMF) administered epicutaneously to rats was examined. The rats were dosed on gestation days 6-15 or on gestation days 1-20 at dose levels of up to 2 ml DMF kg-1 body weight. Body weight, weight gain and pregnancy rate were reduced in those rats receiving 2 ml DMF kg-1 body weight per day on days 6-15. A reduction in the number of live fetuses and in fetal weight, as well as an increase in postimplantation loss, were also observed at this dose level. Similar but more pronounced effects were observed in rats dosed on days 1-20 with 2 ml DMF kg-1 body weight. The lowest effect level was 1 ml DMF kg-1 body weight. No other dose-related effects were found in this study. PMID- 2254585 TI - Evaluation of the teratogenic potential of the plasticizer butyl benzyl phthalate in rats. AB - The teratogenicity of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at a dosage of 0, 0.25, 0.5, 1.0 or 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intakes of BBP were 185 mg kg-1 for the 0.25% group, 375 mg kg-1 for the 0.5% group, 654 mg kg-1 for the 1.0% group and 974 mg kg-1 for the 2.0% group. Adjusted maternal body weight gain (body weight gain excluding the gravid uterus) during pregnancy in the 1.0 and 2.0% groups was significantly lowered. Food consumption during pregnancy in the 0.25 and 0.5% groups did not differ from that in the control group. No death was noted in the pregnant females of any group. There was no significant compound-related effects on the incidence of preimplantation loss. All dams given 2.0% BBP exhibited complete resorption of all the implanted embryos. Morphological examinations of the fetuses revealed no evidence of teratogenesis. It could be concluded that the no-observable-effect-levels (NOEL) in rats were 0.5 and 1.0% BBP in the diet for maternal and embryofetal toxicity, respectively. PMID- 2254586 TI - Formation of methemoglobin and metmyoglobin using 8-aminoquinoline derivatives or sodium nitrite and subsequent reaction with cyanide. AB - The kinetics of the oxidation of hemoglobin (Hb) and myoglobin (Mb) by sodium nitrite, 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-quinoline diphosphate (primaquine), 6-methoxy-8-(6-diethylaminohexylamino)-4-methyl-quinoline dihydrochloride (WR6026) and 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4 methyl- 5-[(3-trifluoromethyl)phenoxy]quinoline succinate (WR238,605) were studied at pH values ranging from 7.4 to 7.6 and at 37 +/- 1 degrees C. The reaction between Hb and primaquine, WR6026 and WR238,605 resulted in precipitation, as did the reaction between Mb and WR238,605. The reaction between nitrite ion (NO2-) and Hb showed a lag period followed by an autocatalytic phase. The data in this study are consistent with and substantiate the proposed mechanism for the Hb-NO2- oxidation reaction. The reaction between Mb and NO2- at higher NO2- concentrations also showed a lag period followed by an autocatalytic period, while at lower NO2- concentrations no lag period was seen. The data suggest a shift in rate constant at these lower NO2- concentrations. The reaction between Mb and both WR6026 and primaquine followed a two-term rate law with oxidant-dependent and -independent terms. Concentration-effect curve data, along with these results, suggest the presence of a catalytic pathway. The rates of formation of cyanomethemoglobin and cyanometmyoglobin complexes from cyanide ion and methemoglobin (MHb) and metmyoglobin (MMb), respectively, were followed in the presence of the heme oxidants. The rate constants were all within a narrow range and suggest that complexation of cyanide by MHb and MMb is not affected by the presence of oxidants. PMID- 2254587 TI - No evidence of toxicity or carcinogenicity of pentaerythritol tetranitrate given in the diet to F344 rats and B6C3F1 mice for up to two years. AB - Toxicology and carcinogenesis studies of pentaerythritol tetranitrate (PETN), an organic nitrate used in explosives and as a therapeutic agent for angina pectoris, were conducted by administering diets containing PETN,NF (National Formulary Grade, a 1:4 mixture of PETN and lactose) to both sexes of F344 rats and B6C3F1 mice in 14-day, 13-week and 2-year studies. PETN was found to be essentially non-toxic in 14-day and 13-week studies at dietary concentrations as high as 10,000 ppm; the weight gain of female rats was lower than that of controls at 5000 and 10,000 ppm in the 13-week study. In the 13-week studies, one in ten high-dose female rats had an adenoma of the Zymbal gland and one in ten high-dose female mice had a hepatocellular adenoma. Dietary concentrations chosen for the 2-year studies were 5000 and 10,000 ppm for male rats and male and female mice, and 1240 and 2500 ppm for female rats. In the 2-year studies, there were no adverse effects on survival or body weight gains in either sex of rats or mice. No neoplastic or non-neoplastic lesions were considered to be related clearly to PETN administration. Neoplasms of the Zymbal gland occurred at low incidences in PETN-exposed groups of both sexes of rats in the 2-year study. PMID- 2254588 TI - Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 1. Hydrochlorothiazide. AB - Toxicology and carcinogenesis studies of hydrochlorothiazide, a benzothiadiazide diuretic, were conducted by administering diets containing the drug to both sexes of F344 rats and B6C3F1 mice in 15-day, 13-week and 2-year studies. No rats died during the 15-day or 13-week studies at dietary concentrations of up to 50,000 ppm. Deaths of male mice in the top dose group in the 13-week study were likely to be related to chemical administration. In the prechronic studies, increased nephrosis and mineralization at the kidney corticomedullary junction were the primary toxic effects of hydrochlorothiazide observed in rats. In mice, chemical related effects included nephrosis and calculi, inflammation and epithelial hyperplasia in the urinary bladder. In 2-year studies using dietary concentrations of 0, 250, 500 and 2000 ppm in rats and 0, 2500 and 5000 ppm in mice, survival of dosed and control groups of rats and mice was similar, as were body weights of mice. Dosed groups of male and female rats were uniformly lighter than controls (up to 25%) throughout the studies. Severe chronic renal disease with secondary parathyroid hyperplasia and fibrous osteodystrophy of the bone were attributed to chemical administration in rats. No neoplasms in rats or female mice or non-neoplastic lesions in mice were associated with hydrochlorothiazide. In high-dose male mice, liver neoplasms were increased but were not considered to be related to hydrochlorothiazide administration because of an unusually low incidence in the control group relative to historical controls. PMID- 2254589 TI - Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 2. Furosemide. AB - Toxicology and carcinogenesis studies of furosemide, a widely used diuretic, were conducted by administering diets containing the drug to both sexes of F344 rats and B6C3F1 mice in 14-day, 13-week and 2-year studies. Deaths occurred among rats and mice receiving diets containing 46,000 ppm furosemide in 14-day studies, and animals given diets containing lower concentrations lost weight. No deaths were seen in 13-week studies using top concentrations ranging from 10,000 to 20,000 ppm, but animals at higher concentrations had lower weight gains than controls. Nephrosis in rats and mice was the only significant compound-related lesion observed in the prechronic studies. In 2-year studies, rats received diets containing 0, 350 or 700 ppm furosemide and mice received diets containing 0, 700 or 1400 ppm furosemide. Survival of dosed and control rats of both sexes and male mice was similar; survival of high-dose female mice was lower than controls. Nephropathy was increased in male rats and in male and female mice. In female mice, increased malignant tumors of the mammary gland were associated with furosemide administration. In male rats, marginal increases in tubular cell neoplasms of the kidney and in meningiomas of the brain were observed in dosed animals, but these were not considered to be related clearly to exposure to furosemide. PMID- 2254590 TI - The effect of sodium tetrathionate on cyanide conversion to thiocyanate by enzymatic and non-enzymatic mechanisms. AB - Sodium tetrathionate has been proposed as a cyanide antidote despite its reported toxicology and inhibitory effect on rhodanese. We investigated the effect of tetrathionate and an analog, dithionite, on rhodanese activity because of their structural similarity to thiosulfate, a known sulfane sulfur donor for this enzyme. Rhodanese activity of guinea pig liver homogenate was assayed by measuring the formation of ferric thiocyanate complex at 460 nm. With thiosulfate as a substrate, the Km for rhodanese was 6.7 mM and the Vmax was 0.67 mumol thiocyanate min-1 mg-1 protein. The conversion of cyanide to thiocyanate by rhodanese was inhibited in the presence of tetrathionate at the millimolar concentration (e.g. 1 mM) range. Dithionite had a negligible effect on rhodanese activity. Neither thiosulfate (1-100 mM) nor dithionite produced significant amounts of thiocyanate from cyanide spontaneously (i.e. non-enzymatically). However, in the absence of rhodanese, tetrathionate (1.0, 10.0 and 100.0 mM) produced a dose-dependent increase in thiocyanate. These data suggest that tetrathionate detoxifies cyanide non-enzymatically, which may, in part, account for its antidotal effects. PMID- 2254591 TI - Biochemical and histopathological changes following dermal exposure to paraphenylene diamine in guinea pigs. AB - The guinea pigs were dermally exposed to paraphenylene diamine (PPD) at a dose level of 0.1 ml day-1 of a 1.0% (w/v) solution of PPD for 1, 3, 5 and 7 days. The absorption of PPD and its effects on lipid peroxidation, glutathione, histamine and several enzymes were assessed in skin and serum. Histopathological changes in liver, kidney and skin were examined also. The findings of the study indicated that PPD exposure resulted in significantly increased levels of lipid peroxidation and histamine contents in skin. The activity of enzymes increased significantly in skin and serum. PPD exposure also showed degenerative changes in liver and hyperkeratosis together with infiltration of cells in the dermis. Biochemical defects and histopathological changes in skin and serum correlated with the duration of exposure. PMID- 2254592 TI - Laugh it off. The effect of humor on the well-being of the older adult. AB - 1. Laughter releases excessive physical and psychological energy, and it reduces stress, anxiety, worry, and frustration. Humor as a skillful nursing intervention can enhance the overall well-being of older adults. 2. If the timing is inappropriate, humor can be a destructive rather than constructive intervention, especially in nursing situations where embarrassing, sensitive, or emotion-laden issues are at hand. 3. This study found that as one ages, one's self-perception of health seems to decrease. Therefore, nurses need to promote a positive outlook toward the aging process and one's own health status while interacting with the elderly in a variety of settings. 4. Nurses should be encouraged to explore the use of humor, not only with patients of all ages, but also with their nurse colleagues to help reduce burn out; to cope with the everyday stress and pressures inherent in the profession; and to enhance learning in the classroom. PMID- 2254593 TI - The PALS program. Intergenerational remotivation. AB - Social isolation is a major problem for the institutionalized elderly. An intergenerational geriatric remotivation program is one method to stimulate social awareness and functioning. Data analysis revealed the construct of invitational work as describing the social behaviors of children and elders during the program sessions, and the basic social psychological process of reconnecting as referring to what certain elders did in the Pals Program and to what the program meant to the elders. Although touted as a panacea for social isolation of elders, intergenerational remotivation programs are revealed in this research to be quite complex and even problematic. To be successful in decreasing social isolation, such programs require ongoing staff monitoring and interventions. PMID- 2254594 TI - Back to the beginning. Nursing case management of the older client with alaryngeal speech needs. AB - A laryngectomy is a devastating event with many responses, the most dramatic of which is the loss of normal voice production. The three most common methods of alaryngeal speech are esophageal speech, artificial larynx, and tracheoesophageal puncture. A nurse case manager who functions as coordinator of formal and informal support systems will help ensure the outcome of satisfactory alaryngeal speech for older laryngectomees. PMID- 2254595 TI - Spiritual needs: a forgotten dimension of care? PMID- 2254596 TI - Do drugs affect social behavior in the confused elderly? AB - Mental confusion in the elderly can be manifested by impairments in the areas of memory, orientation, concentration, and judgment. The number and classification of drugs prescribed for elderly residents of nursing care facilities can contribute to the development of mental confusion. As the number of drugs prescribed for confused elderly increases, the potential for these persons to engage in group social behavior decreases. PMID- 2254597 TI - Toe the line: a nurse-run well foot care clinic. AB - 1. Adequate foot inspection requires good vision and joint mobility, both of which tend to decline with age. In addition, medical records suggest that health care workers typically do not consider foot care a priority. 2. A major focus of discharge planning is functional status and mobility, of which the feet play a major role. Nurses must endeavor to look at the total person and address the client's primary concern. 3. Foot care assessment, intervention, and teaching is a unique opportunity for nurses to independently and positively affect the specialized health-care system toward viewing and caring for the client as a whole. PMID- 2254598 TI - Ease of continuous dermal suture removal. AB - The purpose of this investigation is to identify the synthetic nonabsorbable monofilament suture that requires the lowest forces for removal of continuous dermal sutures. Immediately after wound closure, continuous dermal polypropylene sutures require the lowest suture removal forces. The ease of polypropylene suture removal from continuous dermal skin closure is related to the suture's low surface coefficient of friction. PMID- 2254599 TI - Effects of nonparticipation in trauma center system on emergency department utilization. AB - The University of Illinois Hospital (UIH) serves an inner-city urban population in one of the highest crime rate districts in Chicago. On May 20, 1986, the city's Level I Trauma ordinance took effect with the University of Illinois Hospital declining to participate. To measure the impact of the ordinance on a nonparticipating hospital, we undertook a retrospective analysis of our trauma patient utilization statistics. Consecutive monthly patient census data of 71 months was compiled with emphasis on patient presenting complaints and related subspecialty evaluation. We observed significant decreases of patients presenting with head injuries, fractures, and animal bites as well as with major trauma, minor trauma, and general surgery hospital admission. The final disposition of the patients arriving by ambulance was consistent with the observed decrease in major traumatic conditions and in minor traumatic conditions. However, the mean number of patient presentations per day (ppd) admitted to regular medical or surgical beds decreased from 2.70 ppd to 2.30 ppd while the mean number of ppd sent home increased from 2.64 ppd to 3.49 ppd. These data suggest that loss of trauma center status designation has a profound effect on utilization of emergency departments not participating in the trauma system. Nonparticipation appears to be associated with a significant decrease in utilization rates for major and minor trauma patients and a significant increase in the number of patients discharged who had arrived by the Chicago Fire Department Paramedic System (CFD). This effect on the emergency department extends to utilization of inpatient services. PMID- 2254600 TI - Sudden death associated with undiagnosed Graves' disease. AB - Hyperthyroidism may result in multiple symptoms attributable to an excess of thyroid hormone. We report a case of Graves' disease in association with sudden death in a previously healthy, undiagnosed young female. This case illustrates an unusual initial presentation of Graves' disease. PMID- 2254601 TI - Sphenoid sinusitis, a cause of debilitating headache. AB - We present a case of sphenoid sinusitis resulting in a debilitating headache refractory to both oral and intramuscular analgesics. Despite an aggressive evaluation in the emergency department, the correct diagnosis and appropriate treatment were delayed. Recognition of sphenoid sinusitis, the complications associated with it, and the need for aggressive management are addressed. PMID- 2254602 TI - Sialolithiasis: case studies and review. AB - Three cases of sialolithiasis are presented, each representative of acute and chronic presentations of this problem. The evaluation and treatment of salivary gland and duct stones are outlined. The primary axiom is, "Treat the gland, not the stone," and the essential aspects of emergency medical management are antibiotics, sialogogues, warm compresses, mechanical stimulation, and appropriate referral to an otolaryngologist. PMID- 2254603 TI - Leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry. AB - Leukemic patients with extremely high white blood counts may exhibit the phenomenon of leukocyte larceny, in which white blood cells metabolize plasma oxygen in arterial blood gas samples (ABG) producing a spuriously low oxygen tension. We report the case of a leukemic patient with a white blood count in excess of 500,000 in whom multiple ABGs documented hypoxemia out of proportion to his clinical picture. Pulse oximetry was used to confirm higher hemoglobin oxygen saturation to establish the leukocyte larceny. PMID- 2254604 TI - Blepharospasm-oromandibular dystonia associated with a left cerebellopontine angle meningioma. AB - Blepharospasm-oromandibular dystonia is characterized by the presence of spasms of the orbicularis oculi (blepharospasm) and of the lower facial or oromandibular muscles. A patient with this syndrome is presented in which a left cerebellopontine angle meningioma appeared to act as a triggering mechanism for the development of this disorder. On the basis of this report, we recommend that physicians search for this tumor in patients with this disorder. PMID- 2254605 TI - Changes affecting the initial evaluation and care of the pregnant trauma victim. AB - Pregnant women in American society today are at significant risk of injury during a period when physiologic responses to trauma, as well as expected findings of physical examination and laboratory evaluation are altered by the on-going pregnancy. Changes in anatomy, hemodynamics, respiratory function, gastrointestinal function, and hematologic and hemostatic parameters impact upon the approach to the evaluation and management of injured pregnant women. Maternal outcome is dependent on the nature and extent of injury and on the delivery of appropriate care. Fetal outcome relates to the magnitude of direct injury and the maternal physiologic response. It is imperative that all physicians involved in clinical evaluation and management of injured pregnant women understand the changes engendered by pregnancy and their effects upon the mother, the fetus, and the decision-making process. The best way to secure a favorable outcome for both mother and fetus is a standardized planned approach to care provided by a team cognizant of these changes. PMID- 2254606 TI - Case report: severe ethylene glycol intoxication with normal osmolal gap--"a chilling thought". AB - This is a case of a 23-year-old male presenting with altered sensorium, vomiting, and right flank pain. Despite a normal osmolal gap, he was found to be suffering from ethylene glycol intoxication. This little-described presentation can result in the clinician failing to consider ethylene glycol as a causative agent. PMID- 2254607 TI - Analysis of base station morphine orders: assessment of supervising physician consistency. AB - Paramedic contact with a base station should gemerate consistent recommendations reflecting a consensus of base station physician care. In our urban EMS system, paramedics must contact a single base station to provide morphine sulfate (MS) for a patient with chest pain. We performed a retrospective cohort analysis of all prehospital MS requests for chest pain to determine the consistency of the circumstances for which the paramedic team was refused MS. These MS requests represented 123 of the 1,715 (7%) on-line physician consultations during the 6 month study. Only 15 of the 123 (12%) MS requests were refused. Neither the mean patient age, sex distribution, or presenting vital signs correlated with MS refusal. A maximum estimate of transport time to the hospital of less than or equal to 5 minutes was noted for 7 of 15 (47%) medication refusals compared to only 11 of 96 (11%) approvals with documented estimated transport times (P less than or equal to 0.005). A simultaneous request for nitroglycerin (NTG) was noted for 6 of the 15 (40%) medication refusals and 15 of the 108 (14%) approvals (P less than 0.05). We found refusal of MS administration to be uncommon. Supervising physicians tended to refuse MS when the transport time was short and when NTG was requested for concomitant administration. We also noted physician inconsistencies in refusal scenarios. These findings can guide physician consensus development to avoid sending mixed messages to paramedics. PMID- 2254608 TI - Definition and classification of disasters: introduction of a disaster severity scale. AB - In disaster medicine, a meaningful definition of the word disaster is lacking. A simple definition, using only two criteria, is proposed. Added to this, a classification scheme is formulated. Based on this definition and classification, a disaster severity scale is introduced. The methodology used is described, and the significance of these proposals is discussed. PMID- 2254609 TI - The electrocardiographic manifestations of cyclic antidepressant therapy and overdose: a review. AB - Cyclic antidepressants may cause changes in the electrocardiogram at therapeutic or toxic serum levels. The most serious complications of cyclic antidepressant toxicity are dysrhythmias, hypotension, and seizures. It is predominantly the cardiotoxic effects that cause mortality. Once cardiotoxicity is evident, the treatment of choice is serum alkalinization, preferably by sodium bicarbonate therapy. In order to predict which overdose patients are at high risk for complications, electrocardiographic criteria have been identified as reliable screens. For "first generation" tricyclic antidepressants, QRS prolongation (particularly greater than 100 msec) and a terminal 40-ms frontal plane axis greater than 120 degrees are the most sensitive. This article reviews antidepressant pharmacology, electrocardiographic manifestations of antidepressant cardiotoxicity, and approaches to treatment of antidepressant induced conduction disturbances and dysrhythmias. PMID- 2254610 TI - The electrocardiogram in chronic obstructive pulmonary disease. AB - The electrocardiogram is often abnormal in patients who have chronic obstructive pulmonary disease. The most frequent abnormalities are a rightward P-wave axis (greater than or equal to 70 degrees) and a rightward QRS axis (greater than or equal to 90 degrees). In addition, low voltage in the limb leads, an S1S2S3 pattern, poor R-wave progression, a posterior-superior terminal QRS vector or other changes may be present. Transient atrial and ventricular dysrhythmias are common. Knowledge of the usual electrocardiographic manifestations of chronic obstructive pulmonary disease enables the clinician to recognize uncharacteristic abnormalities, which often represent the effects of superimposed illnesses or drug toxicity. PMID- 2254611 TI - Blunt trauma to the heart: the pathophysiology of injury. AB - Blunt injuries to the heart are common and potentially lethal. These injuries often go undetected while more obvious problems are treated. A cardiac injury should be suspected in any patient who sustains severe chest trauma. The spectrum of cardiac trauma ranges from injuries with no actual cellular damage (myocardial concussion) to cardiac chamber rupture. The pathophysiology, diagnosis, and treatment of these injuries are discussed. PMID- 2254612 TI - The scapular manipulation technique for the reduction of acute anterior shoulder dislocations. AB - Anterior shoulder dislocations are a common occurrence in busy emergency departments. Numerous techniques for treating this problem have been reported. The majority of these techniques use traction and leverage of the humerus, often requiring considerable force and causing significant patient discomfort. We report a simple, relatively painless, and atraumatic method of shoulder reduction involving manipulation of the scapula as well as the humerus. This technique has been used in our emergency department with considerable success and no complications. PMID- 2254613 TI - Horner's syndrome in the emergency department. AB - We present a case of a 47-year-old female who was followed for 7 months with complaints of musculoskeletal pain involving the shoulder and scapula until she presented to the emergency department with Horner's syndrome and was diagnosed as having a superior pulmonary sulcus tumor. A review of the literature shows that although such tumors are a frequent cause of Horner's syndrome there are numerous other benign as well as malignant causes of Horner's syndrome. The differential diagnosis can be significantly narrowed by a knowledge of the anatomy and a careful physical examination. We present the anatomy, pathophysiology, differential diagnosis, and evaluation of patients who present to the emergency department with Horner's syndrome. PMID- 2254614 TI - Sven Ivar Seldinger: catheter introduction on a flexible leader. AB - The Seldinger method of guide-wire catheterization was originally described by Sven Ivar Seldinger, a Swedish radiologist, as an arterial cannulation method for performing arteriography. Subsequent modifications have adapted the technique for use in venous catheterization. The major advantage of the Seldinger technique is that it allows for the insertion of a catheter that is larger in diameter than the needle utilized. Its principle use in emergency medicine has been in central venous cannulation, but the guide wire technique has also found utility in peripheral arterial cannulation, percutaneous transtracheal ventilation, and diagnostic peritoneal lavage. PMID- 2254615 TI - Voice from another room. PMID- 2254616 TI - Accuracy versus precision. PMID- 2254617 TI - Reflections on grief. PMID- 2254618 TI - Reviewing cyclic antidepressant cardiotoxicity: wheat and chaff. PMID- 2254619 TI - Observation units--a step out of the emergency department. PMID- 2254620 TI - Urine sampling in ambulatory women. PMID- 2254621 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: hand surgery. AB - This is the fifth article in a continuing series on objectives to direct the training of emergency medicine residents. The emergency physician frequently must deal with hand injuries. Often these may appear innocuous; recognition of these injuries requires certain technical skills and a working knowledge of these entities. Specific objectives presented provide guidance for the didactic content as well as skill mastery for the resident experience. PMID- 2254622 TI - Physicians should be expert witnesses. AB - Physicians have a responsibility to society, their peers, and patients to participate in malpractice litigation in a manner that ensures that medical malpractice cases are properly evaluated. Physicians are reluctant to involve themselves as expert witnesses in medical malpractice litigation because of not wanting to further any malpractice suits, mistrust of attorneys and misconceptions about expert witnesses and the legal system in general. The expert witness should be an impartial practicing physician who can select those suits that should or should not be filed and identify which parties were negligent in each case. If impartial physicians do not evaluate cases for attorneys, other more partisan and less objective physicians will. PMID- 2254623 TI - Branched chain amino acids in the management of chronic liver disease. Facts and fantasies. AB - The liver plays a central role in protein and amino acid metabolism. It processes dietary amino acids and reprocesses amino acids released from muscle protein degradation. It utilises amino acids for protein synthesis and gluconeogenesis, regulates the supply of amino acids to peripheral tissues and converts excess amino acids to urea. In patients with liver disease the liver's ability to control both plasma and tissue amino acid fluxes may be seriously disturbed. The resultant changes in amino acid metabolism may be implicated in the genesis of the neuropsychiatric abnormalities and the deterioration in nutritional status commonly observed in patients with hepatic failure. Thus, on theoretical grounds, amelioration of these amino acid abnormalities might benefit patients with liver disease who have hepatic encephalopathy or are malnourished. However, there is, at present, no consensus as to the efficacy, practicality or cost-effectiveness of 'amino acid therapy' in patients with liver disease. PMID- 2254624 TI - Prostaglandins and the treatment of hepatorenal syndrome in cirrhosis. PMID- 2254625 TI - Alterations of hepatocellular peroxisomes in viral hepatitis in the mouse. AB - In addition to being found in peroxisomal diseases, peroxisomal alterations are also seen in viral hepatitis, though quantitative data are lacking. Experiments were performed on BALB/c mice. These mice were infected with Mouse Hepatitis Virus type 3 or were starved. The peroxisomes were cytochemically stained for catalase. Light microscopic, ultrastructural and morphometric analysis were performed. Several peroxisomal changes were observed 24 h after infection, and these changes became more pronounced after 40 h. There was a decrease in catalase activity, which was more pronounced in some regions, in some cells and in individual organelles; and there was also the onset of a progressive decrease in the number of organelles. It is believed that peroxisomes disappear by lysis. Proliferation probably occurs simultaneously up to 40 h after infection. At 48 h, necrotic foci are found to have swollen peroxisomes, and thus destruction is enhanced. Although peroxisomes seem to be sensitive markers of hepatic injury, they show a heterogeneous reaction pattern. Our results are discussed in relation to human viral hepatitis. PMID- 2254626 TI - Subfractionation of serum bilirubins by alkaline methanolysis and thin-layer chromatography. An aid in the differential diagnosis of icteric diseases. AB - The determination of direct and indirect-reacting bilirubin fractions by diazo procedures does not allow a definite diagnosis of icteric diseases. Therefore, the clinical relevance of serum bilirubin subfractionation by alkaline methanolysis and subsequent thin-layer chromatography (AM-TLC) was evaluated. Esterified bilirubins could be detected and quantitated in all serum samples investigated. The ratio of serum esterified to total bilirubin was 10-28% in 60 healthy adults (mean 17 +/- 5% S.D.), 1-11% in 77 patients with Gilbert's syndrome (mean 6 +/- 2%), and 2 and 3%, respectively, in two patients with Crigler-Najjar disease type II. The difference was highly significant (p less than 0.001) and the overlap was restricted to three of 139 individuals. The ratio of esterified to total bilirubin was similar to that obtained with HPLC when corrected for with a blank run. The absolute concentration of bilirubin esters in serum from Gilbert's syndrome patients was similar to that from healthy controls, but the unconjugated pigment was increased. In patients with chronic haemolysis (n = 9) and chronic persistent hepatitis (n = 12), the hyperbilirubinaemia consisted of a proportional increase of both unconjugated and esterified bilirubin. As such, the ratio of conjugated to total bilirubin was not significantly different from control values. Patients with acute hepatitis during the first (n = 18) and third ('remission') week of the disease (n = 15), liver cirrhosis (n = 34), and extrahepatic cholestasis (n = 20) predominantly showed an increase in bilirubin conjugates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254627 TI - Influence of backward perfusion on ursodeoxycholate-induced choleresis in isolated in situ rat liver. AB - Ursodeoxycholate-induced bicarbonate-rich hypercholeresis was studied in isolated in situ forward- or backward-perfused rat livers. Both spontaneous bile flow and bile acid secretion were similar regardless of the direction of the perfusion. The choleretic effect of tauroursodeoxycholate infusion (400 nmol.min-1.100 g-1 body weight) was not significantly different in forward- or backward-perfused livers either. Ursodeoxycholate infusions at low rate (800 nmol.min-1.100 g-1 body weight) induced similar bile flow, bile acid output and bicarbonate output in both forward- and backward-perfused livers. Net ursodeoxycholate uptake, measured as [14C]ursodeoxycholate uptake over the bile acid infusion period (30 min), was not significantly different during forward- or backward-perfusion (4.8 and 5.1 mumol/g liver, respectively); i.e., approx. 67% of infused dose (approximately 7.5 mumol/g liver per 30 min). A 2-fold increase in the dose of ursodeoxycholate infusion (1600 nmol.min-1.100 g-1 b.wt.) induced additional enhancement in both bile flow and bicarbonate biliary secretion, but not in bile acid uptake or output, in forward-perfused livers. Moreover, infusion of the same dose of ursodeoxycholate to backward-perfused livers had a significantly lower choleretic effect (-29%, p less than 0.001) even though ursodeoxycholate uptake and biliary output were similar regardless of perfusion direction. Net ursodeoxycholate uptake, was only 2.4 mumol/g liver; i.e., approx. 16% of infused dose (approximately 15 mumol/g liver per 30 min). These findings indicate that a process related with the hepatic microanatomy may be involved in the hypercholeretic response to ursodeoxycholate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254628 TI - Liver cell damage and lysosomal iron storage in patients with idiopathic hemochromatosis. A light and electron microscopic study. AB - Eleven patients with idiopathic hemochromatosis were subjected to percutaneous liver biopsy, and seven were rebiopsied after repeated phlebotomies. The liver tissue was examined by light and electron microscopy. Ultrastructural morphometry was also performed and iron content was determined. Initially, all biopsies displayed large iron-laden lysosomes in the hepatocytes. Lysosomal volume density was increased and correlated well with liver iron content (r = 0.84, p less than 0.005). Neither mitochondria nor the endoplasmic reticulum showed any ultrastructural changes, except in the necrotic cells of biopsies with the highest liver iron content. In these cases, iron-laden lysosomes were also encountered in the Kupffer cells. Following treatment, liver iron content and lysosomal volume density were normalized. More specifically, iron content was 14.1 +/- 2.1 micrograms Fe/mg protein before and 1.3 +/- 0.3 micrograms Fe/mg protein after treatment (p less than 0.001). Lysosomal volume density was 6.1 +/- 0.8% before and 1.8 +/- 0.2% after treatment (p less than 0.001). Hence, in the precirrhotic stage of idiopathic hemochromatosis, the first evident ultrastructural changes are in the lysosomal compartment. These changes correlate well with the iron overload, also in advanced stages of the disease, and are reversed after iron removal. PMID- 2254629 TI - Cystic dilatation of intrahepatic bile ducts in primary sclerosing cholangitis. AB - A case of primary sclerosing cholangitis associated with cystic dilatations of intrahepatic bile ducts simulating Caroli's disease is described. The diagnosis of primary sclerosing cholangitis was based upon cholangiogram features, liver histologic examination and the association with chronic ulcerative colitis. It may be suggested that the cystic dilatation of intrahepatic bile duct represents an extreme form of the usual mild dilatations (cholangiectases) described in primary sclerosing cholangitis. We suggest that cystic dilatation of intrahepatic bile ducts could be included among the radiologic features of this disease. PMID- 2254630 TI - Activities of free oxygen radical scavenger enzymes in human liver. AB - Activities of superoxide dismutase, catalase and glutathione peroxidase were measured in liver biopsy specimens from patients with various liver diseases, including six with chronic persistent hepatitis, nine with chronic active hepatitis, nine with non-alcoholic cirrhosis, eight with alcoholic cirrhosis and eight with acute hepatitis. Measurements from ten patients without liver disease were used as controls. Levels of total superoxide dismutase activity in the chronic active hepatitis and non-alcoholic cirrhosis groups were significantly lower than those in the controls (p less than 0.01 and p less than 0.01, respectively). The level of total superoxide dismutase activity in the acute hepatitis group was significantly higher than that in the control group (p less than 0.01). The levels of Cu,Zn-superoxide dismutase activity in all the experimental groups, except for the chronic persistent hepatitis group, were significantly lower than those in the controls (p less than 0.01 in all groups). The levels of Mn-superoxide dismutase activity in the alcoholic cirrhosis and acute hepatitis groups were significantly higher than those in the controls (p less than 0.01 and p less than 0.01, respectively), although no difference in the level of this enzyme was seen among the controls, chronic persistent hepatitis, chronic active hepatitis and non-alcoholic cirrhosis groups. The levels of catalase activity in the groups with chronic active hepatitis, non-alcoholic and alcoholic cirrhosis and acute hepatitis were significantly lower than those in the controls (p less than 0.01 in all groups). Glutathione peroxidase activity showed no difference among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254631 TI - Modulation of extracellular matrix components during dimethylnitrosamine-induced cirrhosis. AB - Liver fibrosis was induced in rats after administration of dimethylnitrosamine (DMN) intraperitoneally three times a week for 3 weeks. Incomplete septa appeared after 7 days and evidence of nodulation of the parenchyma was observed after 21 days. Both distribution of extracellular matrix components (collagen type I, type III and type IV, laminin, fibronectin, heparan sulphate proteoglycan) and the distribution of desmin as a marker of lipocytes (Ito cells) and of iso-alpha smooth muscle actin were studied with immunoperoxidase. Changes in the distribution of extracellular matrix components outlined both the formation of septa and the development of nodules with changes in the sinusoidal pattern evoking aspects of capillarization. The number of desmin-positive cells increased in DMN-treated animals, showing a prominent reaction in the fibrous septa. In the normal liver, lipocytes were positive for laminin and negative for actin, but septal and juxta-septal lipocytes were positive for both antigens, suggesting the presence of transitional cells with mixed immunoreactivity. This was confirmed by ultrastructural studies which showed typical intraseptal myofibroblasts and other elements exhibiting the structural features of both myofibroblasts and lipocytes. PMID- 2254632 TI - The effect of non-protein liquid meals on the hepatic venous pressure gradient in patients with cirrhosis. AB - It has been suggested that protein feeding increases portal pressure in cirrhotic patients, but that carbohydrate and fat have little effect. We examined the relationship between feeding and portal pressure, using different liquid test meals (250 or 500 ml non-protein, 250 ml protein-containing, 500 ml water), in 29 alcoholic patients with cirrhosis and portal hypertension. The mean hepatic venous pressure gradient (HVPG) increased significantly 30 min after the protein meal (10% increase; p = 0.009) and returned to basal levels at 60 min. The mean HVPG also increased significantly after the non-protein meal: after 500 ml the increase was 23% at 30 min (p = 0.046) and 17% at 60 min (p = 0.12); and after 250 ml it was 15% at 30 min (p = 0.012) and 7% at 60 min (p = 0.05). Ingestion of 500 ml water caused a small, non-significant, increase in mean HVPG. Plasma glucagon levels increased significantly at 30 and 60 min after the protein meal, but did not change significantly after the non-protein meal or water. Both protein-containing and non-protein meals significantly elevate HVPG in alcoholic patients with cirrhosis and portal hypertension. PMID- 2254633 TI - Effect of various organic anions on the plasma disappearance of 1-anilino-8 naphthalene sulfonate. AB - The effects of various organic anions on the hepatic transport of an anionic fluorescent dye, 1-anilino-8-naphthalene sulfonate (ANS) were investigated by measuring the plasma disappearance-time profiles in rats. Ten min after the i.v. administration of ANS (3 mumol/kg), various organic anions (60 mumol/kg) were injected in a bolus. Sulfobromophthalein (BSP), bromophenol blue (BPB) and rose bengal (RB) induced a transient increase in the plasma concentration of ANS (the so-called 'counter-transport' phenomena). The effect of rose bengal was somewhat different. After the administration of rose bengal, the plasma concentration of ANS decreased rapidly followed by a gradual increase. On the other hand, after the administration of bilirubin and taurocholate, the transient increases in plasma ANS concentrations were minimal. No effect was observed after the administration of phenolsulfophthalein (PSP) or oleate. The effects of these organic anions on the binding of ANS to rat liver cytosols were examined by equilibrium dialysis. Sulfobromophthalein, bromophenol blue and rose bengal, which yielded an in vivo 'counter-transport' phenomena, markedly inhibited ANS binding to cytosolic proteins. On the other hand, the other organic anions examined had very small, if any, inhibitory effect. The ANS binders in the cytosol were then identified by gel filtration. ANS bound mainly to X and Y (ligandin) fractions in the cytosol. Sulfobromophthalein, which is one of the organic anions exhibiting the in vivo 'counter-transport' phenomenon, remarkably inhibited ANS binding to ligandin fraction. It was thus suggested that the in vivo 'counter-transport' phenomena may be also explained by the enhancement of back diffusion due to the displacement of intracellular binding. In conclusion, one should be more cautious in interpreting data obtained from so-called in vivo 'counter-transport' experiments. PMID- 2254634 TI - Hemodynamic effects of dopamine in conscious rats with secondary biliary cirrhosis. AB - Dopamine may be used in cirrhotic patients with renal or circulatory failure, but this drug can also increase the degree of portal hypertension. Hence, the systemic and splanchnic hemodynamic effects of dopamine have been studied in portal hypertensive rats with secondary biliary cirrhosis. The dose-response curves showed that dopamine significantly increased portal pressure at the same dose (80 micrograms min-1 kg-1 body wt.) in normal and biliary cirrhotic rats. Arterial pressure only increased with higher doses of dopamine in rats with biliary cirrhosis (160 micrograms min-1 kg-1 body wt.) while in normal animals it increased (80 micrograms min-1 kg-1 body wt.). Dopamine (160 micrograms min-1 kg 1 body wt.) significantly increased mean arterial pressure in normal and biliary cirrhotic rats. It significantly increased cardiac output in biliary cirrhotic rats from 134 +/- 6 to 153 +/- 7 ml/min but not in normals. Accordingly, systemic vascular resistance increased significantly in normal rats but not in cirrhotics. Portal pressure increased significantly in normal rats from 8.0 +/- 0.3 to 12.1 +/- 0.6 mmHg and in rats with biliary cirrhosis from 15.9 +/- 1.0 to 19.0 +/- 1.3 mmHg. Portal tributary blood flow increased significantly in normal and biliary cirrhotic rats (14.1 +/- 1 to 20.9 +/- 2.3 ml/min and 18.0 +/- 0.9 to 25.5 +/- 1.8 ml/min, respectively). This study shows that an elevated dose of dopamine increases the hyperkinetic syndrome in rats with secondary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254635 TI - Criteria of drug-induced liver disorders. Report of an international consensus meeting. AB - International reporting of adverse drug reactions by pharmaceutical manufacturers to national drug regulatory authorities requires internationally accepted standard definitions of reactions and criteria for assessment of causality. The Council for International Organizations of Medical Sciences (CIOMS) undertook a pilot project to prepare such definitions and criteria, and proposed to use as its model a series of expert consensus meetings organized in France by the pharmaceutical company, Roussel Uclaf, with the participation of the official French network of pharmacovigilance. Under CIOMS auspices, an international meeting was organized to test the feasibility of adapting for international use the outcome of the French consensus meetings on drug-induced liver disorders. The meeting resulted in a series of proposed standard designations of drug-induced liver disorders and criteria of causality assessment. PMID- 2254636 TI - Norfloxacin-induced hepatotoxicity. PMID- 2254637 TI - On the rarity of Cruveilhier-Baumgarten's venous hum. PMID- 2254638 TI - Diclofenac hepatitis. PMID- 2254639 TI - Is schizophrenia what it was? A re-analysis of Kraepelin's and Bleuler's population. AB - It has been noted that the term "schizophrenia" is now applied to a group in many ways dissimilar to Emil Kraepelin's cases of dementia praecox and Eugene Bleuler's of schizophrenia. No detailed explanation has been offered for the difference. This article offers evidence that Kraepelin's and Bleuler's concepts were derived from a population largely suffering from organic disorders including the Parkinsonian sequelae of encephalitis lethargica; it describes the conceptual confusion which followed the introduction of the concept of post-encephalitic Parkinsonism and discusses some implications for the modern concept of schizophrenia. It is suggested that the differences between earlier and later groups of schizophrenics may be accounted for by the decline in prevalence of post-encephalitic Parkinsonism and of the neurological and behavioral sequelae of other diseases, and by the parallel unsystematic development of the concept of schizophrenia. PMID- 2254640 TI - The imagination and psychological healing. AB - As one of the internal senses or inward wits, the imagination was long thought to play a crucial role in the age-old struggle between the rational and the irrational, and it was conceived of as a faculty that might be damaged in some forms of psychopathology. During the Renaissance it emerged as a force or factor with a considerable potential for causing harm in the form of disease and for doing good in the form of curing disease. Its place in psychological healing has been significant for much of the time since then, including a lively attention to it in the work of Carl Jung and in the guided imagery techniques of recent decades. PMID- 2254641 TI - Localization and release of homocysteic acid, an excitatory sulfur-containing amino acid. AB - In addition to the excitatory role played by the amino acid transmitters glutamate and aspartate in the central nervous system, their sulfur-containing analogues homocysteic acid (HCA) and cysteine sulfinic acid (CSA) may also play a similar role. HCA is released and taken up by rat CNS tissue; it excites neurons predominantly via NMDA receptors whenever present, and is neurotoxic. The pattern of HCA-like immunoreactivity in the rat indicates a localization of HCA mostly in glial elements, although its presence in nerve terminals and neuronal perikarya cannot be excluded. In the cerebellum of newborn and adult animals, the Bergmann glial cells and the astrocyte endfeet are immunoreactive, either in the presence or in the absence of climbing fibers. In the cortex, hippocampus, and retina, labeling is seen in both glial and neuronal elements. Excitatory signaling involving glial elements is discussed. PMID- 2254642 TI - Symposium and workshop from the third joint meeting of Histochemistry and Cytochemistry and the Histochemical Society. August 8-11, 1990, Seattle, Washington. Proceedings. PMID- 2254643 TI - Workshop on high-resolution immunocytochemistry of cell surfaces using field emission SEM. PMID- 2254644 TI - Optimizing parameters for correlative immunogold localization by video-enhanced light microscopy, high-voltage transmission electron microscopy, and field emission scanning electron microscopy. AB - Correlative video-enhanced light microscopy, high-voltage transmission electron microscopy, and low-voltage high resolution scanning electron microscopy were used to examine the binding of colloidal gold-labeled fibrinogen to platelet surfaces. Optimal conditions for the detection of large (18 nm) and small (3 nm) gold particles are described. PMID- 2254645 TI - Light microscopic autoradiography for study of early changes in the distribution of water-soluble materials. AB - An approach using autoradiography for the study of early changes in the distribution of water-soluble materials and the chemography involved was investigated. Radioactive calcium chloride (45Ca) was injected into the iliac vein of a rat. Ten seconds after the injection the rat was frozen in hexane (-90 degrees C). The frozen rat was embedded in 5% sodium carboxymethyl cellulose and blocked in the coolant. A sheet of plastic tape coated with a synthetic rubber glue was fastened to the trimmed block surface, and whole-body sections 2-10 microns thick were cut with a disposable microtome knife. Selected sections were freeze-dried and then covered with a dried autoradiographic emulsion film about 1 microns thick. The autoradiograph clearly showed the distribution of radioactive calcium in the calcification zone of long bones. The samples chosen to assess chemographic artifacts showed positive and negative chemographies on most of the tissues when these were kept at 23 degrees C, and although both chemographic effects were significantly reduced when the samples were kept at -20 degrees C, cells in several tissues still exhibited positive and negative chemographies. The technique can be used for the study of any animal whose size is suitable for whole-body freeze-sectioning. PMID- 2254646 TI - Ultrastructural immunocytochemical studies of blood group substances in human eccrine glands. AB - We investigated the ultrastructure of blood group antigens A, B, and H in human eccrine glands by means of the immunogold labeling technique. Blood group antigens A, B, and H were found in the Golgi apparatus, secretory granules, and over the apical and basolateral cell membranes of dark cells of eccrine glands depending on the blood group phenotype of the donors. Both A and B antigens were found in the dark cells of AB donors. The labeling pattern of the Golgi stacks seemed to have a polarity whereby the anti-blood group A antibody labeled all the stacks, whereas anti-blood groups B and H bound to the trans side of the Golgi complex. These observations suggest that the blood group substances are secreted into the lumen after being processed through the Golgi apparatus and the immature and mature granules in the dark cells of human eccrine glands. PMID- 2254647 TI - A novel polyclonal antibody (CL-B1/29) for immunolocalization of transforming growth factor-beta 2 (TGF-beta 2) in adult mouse. AB - A polyclonal antibody (CL-B1/29) raised against a synthetic peptide with an amino acid sequence identical to the first 29 N-terminal residues of bovine bone derived transforming growth factor-beta 2 (TGF-beta 2) was characterized and used for immunolocalization of TGF-beta 2 in adult mice. Reduced staining of immunoblots and tissue after absorption of the antiserum with the immunizing peptide or with TGF-beta 2 but not with purified TGF-beta 1 demonstrated that the reagent is specific for TGF-beta 2, with little or no crossreactivity with TGF beta 1. The immunolocalization of TGF-beta 2 was investigated in formalin-fixed, paraffin-embedded cultured cells and murine tissue. Specimens pre-digested with testicular hyaluronidase demonstrated immunostaining predominantly of extracellular connective tissue matrix, whereas specimens pre-digested with pronase E demonstrated primarily cytoplasmic staining. Immunoreactivity was widely distributed in connective tissue, muscle, adsorptive and secretory epithelia, especially of endocrine tissue, and neural tissue of adult mice. PMID- 2254648 TI - Immunohistochemical detection of cytochrome P450 isoenzymes in cultured human epidermal cells. AB - We used specific monoclonal antibodies (MAb) to human cytochrome P450 isoenzymes to determine the presence of these proteins in human epidermal cells. Two MAb (P450-5 and P450-8) recognize major forms of hepatic cytochrome P450 involved in biotransformation of xenobiotics. A third MAb, to cytochrome P450-9, is not fully characterized. The proteins were determined by the indirect immunoperoxidase technique after fixation with methanol and acetone. Biopsy materials for cultured keratinocytes, i.e., foreskin and hair follicles, contained the two major forms of cytochrome P450. In cultured keratinocytes derived from hair follicles the proteins were undetectable, whereas the keratinocytes derived from foreskin continued to express the two major forms of hepatic cytochrome P450. Cultured human fibroblasts and a human keratinocyte cell line (SVK14) showed staining similar to that of the foreskin keratinocytes. Cytochrome P450-9 was detectable only in human hepatocytes. The results indicate that, under the culture conditions applied, cultured human foreskin cells and the cell line SVK14 continue to express specific cytochrome P450 isoenzymes in culture, in contrast to hair follicle keratinocytes. PMID- 2254649 TI - Co-localization of EGF transcripts and peptides by combined immunohistochemistry and in situ hybridization. AB - There is increasing evidence that autocrine- and paracrine-acting growth factors participate in cell and tissue development, maintenance, and renewal. Recent advances in histochemical techniques have facilitated the localization of growth factor messenger RNAs or polypeptides in tissue sections. However, the spatial relationships between the sites of growth factor transcription, translation, and post-translational processing to functional bioactive peptides have been difficult to correlate because each method of detection requires separate tissue sections. We undertook the simultaneous detection of epidermal growth factor (EGF) transcripts and EGF epitopes by combining immunohistochemistry methods with in situ hybridization. Adult mouse submandibular gland was chosen as a representative model because it contains sites of EGF biosynthesis which may participate in mediating the development, maintenance, and renewal of the organ through autocrine or paracrine mechanism(s). Granular duct (GD) cells demonstrated the presence of both EGF transcripts and EGF peptides. In contrast, the interstitial cells lying adjacent to glandular epithelium also contained relatively high levels of EGF transcripts, although no mature EGF peptides were detected. The experimental approach of co-localization and the resulting data indicate previously unreported sites of EGF transcription in glandular interstitial cells, which may provide molecular information required for the morphogenesis and differentiation of adjacent glandular epithelium. PMID- 2254650 TI - Cellular distribution of prothymosin alpha and parathymosin in rat thymus and spleen. AB - By means of immunohistochemical methods, we have investigated the cellular distribution of prothymosin alpha and parathymosin in rat thymus and spleen, using specific antibodies raised against thymosin alpha-1 and against parathymosin. We observed prothymosin alpha immunoreactivity in lymphoid cells both in thymus and spleen. In the thymus, prothymosin alpha staining was more marked in cortex than in medulla. In the spleen, prothymosin alpha was found in lymphocytes of the periarteriolar lymphatic sheaths and was especially prominent in the germinal centers. Parathymosin immunoreactivity in the thymus was mainly localized in the medulla; positive cells were reticuloepithelial cells from the thymic reticulum and the blood barrier. Thymocytes were negative. In spleen, parathymosin was found in reticular cells arranged in a ring between the periarteriolar lymphatic sheath and the marginal zone. Our results do not support an exclusive role for these peptides as immune system hormones or cytokines. PMID- 2254651 TI - Production of monoclonal antibodies against principal cells of the renal collecting duct by in vitro immunization with unsolubilized antigens. AB - We report the production of monoclonal antibodies (MAb) by an in vitro technique which react with principal cells of the renal collecting duct. Spleen cells were directly simulated in vitro with unsolubilized antigens, i.e., by direct contact with the apical site of cultivated principal cells or by contact with cell fragments. Out of several others two antibodies, IV1 and IV2, were selected, which specifically reacted with the principal cells of the collecting duct. MAbIV1 also reacted with Type A intercalated cells, indicating the existence of a common antigen in the apical membrane of both cell types. Type B intercalated cells were consistently unreactive. All other parts of the uriniferous tubule were also unreactive. In Western blot analysis MAb IV1 showed immunoreactivity with a 40 KD and a 43 KD antigen. Our experiments demonstrate the possibility of producing antibodies against unsolubilized antigens by a simple in vitro technique. The activity of particular lymphocyte in this in vitro system is shown by the specificity of the antibodies. PMID- 2254652 TI - Neuroepithelial cell contacts in 12 days old rat embryo: normal and annulated gap junctions. AB - Neuroepithelial cells in the neural tube of 12 days old rat embryos make contact with each other by extended junctional complexes between their lateral membranes near the luminal surface. In this stage gap junctions are not numerous. Besides these "normal" gap junctions, especially in the upper part of the neuroepithelial cells, annulated gap junctions occur. They seem to originate by an endocytotic process of normal gap junctions with participation of cytoskeletal elements. The content of these annulated gap junctions mainly consists of ribosome-like particles in a high density, but larger particles may also occur. Annulated gap junctions sometimes reveal an intimate contact with the smooth endoplasmic reticulum or with the perinuclear cistern. If present in the perinuclear region the annulated gap junctions show membrane irregularities and other signs which are thought to mark steps of breakdown. Life-cycle and possible functions of the annulated gap junctions during neurulation need further investigation. PMID- 2254653 TI - Ependyma of the goat. I. The third cerebral ventricle: scanning electron microscopy study. AB - Ependymal surface of the III-rd cerebral ventricle of 13 goat-males and females and in the testicular hermaphrodite was studied by means of scanning electron microscope. The ependymal surface structure of infundibular recess is in relation to the sex, in case of females to the ovarian cycle phase and in males to the season. The supraependymal cells were always present with the exception of the "rest" period of males. The smallest number of the SEC was found in females during anestrus period, the highest one during proestrus and in the hermaphrodite. The supraependymal cells of goats resemble mostly the macrophages, the supraependymal neuron-like cells were present on median eminence of all animals and on rostral part of infundibulum of the hermaphrodite. The finding on the hermaphrodite's genital organs resembled the incomplete developed male without the female genital organ traces. The number, topography and external morphology of the SEC, however, were in agreement with the data of goat-females during proestrus. The results of the III-rd cerebral ventricle demonstrate the ependymal tanycytes participation in all processes occurring during the reproduction cycle of goats. PMID- 2254654 TI - Immuno- and histochemical data on changed GABA transmission in aged rat cerebellum. AB - The distribution of gamma-aminobutyric acid-immunoreactivity (GABA-I) and activity of GABA-transaminase (GABA-T) was compared in the cerebellum of young adult (3-month old) and aged (24-month old) Wistar rats. A decrease in the density and staining of GABA-immunoreactive and GABA-T positive nerve cells, fibers and puncta were observed in both cerebellar cortex and nuclei of aged rats as compared to those in young adult rats. In contrast, an increased number of Bergmann glia cell and astrocyte processes and bodies in aged rats were demonstrated in GABA immunostaining and histochemical GABA-T reaction. The changes in GABA-I and GABA-T activity provide evidence for altered GABA transmission during normal aging of rat cerebellum. PMID- 2254655 TI - [Quantitative analysis of the teleost brain: evolutionary and adaptive features of encephalization. II. Primary brain subdivisions]. AB - 1. Frequently there is an opposition between olfactory and visual senses. Fresh water fishes are generally macrosomatic and microptic, marine fishes (especially coral reef fishes) are microsmatic and macroptic while piscivorous pelagic fishes are macrosmatic and macroptic. 2. The importance of the cerebellum is a function of both the fish's activity level and its body size. 3. There is a marked opposition between the diencephalon and the medulla oblongata and a greater one between the non-olfactory-telencephalon (NOT) and the medulla oblongata (MA). Although it is not possible to give an accurate evolutionary significance, the ratio of NOT/MA is low in primitive teleostean fishes and high in more derived species (Acanthuridae and Tetraodontiformes). PMID- 2254656 TI - An experimental study of the retinal projections of the European eel (Anguilla anguilla), carried out at the catadromic migratory silver stage. AB - A radioautographic study of the European eel (Anguilla anguilla) was carried out in ten female specimens at the catadromic migratory silver stage. Terminal arborizations of contralaterally projecting visual fibres were identified in ten hypothalamic structures (area optica preoptica ventralis and the nuclei suprachiasmaticus, opticus hypothalamicus ventromedialis, preopticus magnocellularis lateralis, posterioris lateralis, posterioris dorsalis periventricularis posterioris dorsalis lateralis, posterioris dorsalis medialis, posterioris ventralis lateralis, and posterioris ventralis periventricularis), ten thalamo-pretectal structures (Areas C1 and C2, area optica tractus opticus ventrolateralis and the nuclei dorsolateralis thalami, ventrolateralis thalami pars ventralis, opticus ventralis thalami, geniculatus lateralis, opticus pretectalis partes dorsalis et ventralis, and opticus commissurae posterioris), and in the tectal strata opticum partes externa et interna, fibrosum et griseum superficiale, griseum centrale and album centrale. An accessory optic system was identified, and a contralateral retinal projection to the anterior region of the anterior semicircular torus (n. opticus dorsolateralis mesencephali) was identified. Ipsilateral projections to hypothalamic and thalamopretectal structures were also observed. Apart from the retinal projection to the preoptic area, which is exceptionally important in the silver eel, the general plan of organization of the primary visual centres of this form is comparable to that described in other species of teleost. However, the architecture of some primary visual centres shows characteristics similar to those described in more primitive Actinopterygians. PMID- 2254657 TI - A comparison of quantitative histological changes in different regions of the ageing mouse cerebellum. AB - The number of Purkinje cells per mm and the number of granule cells per mm3 were estimated in the lobus simplex of mice aged 6, 15, 22, 25, 28 and 31 months. The results were compared with similar estimations already carried out in the spinocerebellum and nodulus of the same cerebella. All regions showed a decrease of approximately 30% in Purkinje cell number between 6 and 31 months of age with the decrease occurring between 15 and 31 months. At each age examined the number of Purkinje cells per mm was similar in the spino- and pontocerebellum but significantly smaller in the nodulus. Granule cell density was identical in all parts of the cerebellum at all ages. Molecular layer thickness varied significantly with age in all cerebellar regions but this may be an artefactual variation. Granule layer thickness did not vary with age in either the nodulus or spinocerebellum but there was a significant variation in granule layer thickness, in the pontocerebellum due to a substantial decrease in thickness between 28 and 31 months of age. This might be the result of a loss of granule cells in this region which is not apparent in other parts of the cerebellum. PMID- 2254658 TI - Quantitative and morphological study of cell proliferation during morphogenesis in the trout visual system. AB - Cell proliferation in the retina and tectum was investigated in a teleost (the trout Salmo gairdneri Rich.) at embryonic and larval stages in order to determine the pattern of growth in retinotectal organization. The tritiated thymidine was injected into the coelom: 1 microCi at stage 27 and 30, 2 or 5 microCi at stage 34. The morphological and quantitative analysis of the growth in the retina and tectum indicate the existence of two modes of development. In the retina, the thymidine labelled cells are located in a peripheral area with an important dorso ventral asymmetry near the optic disc. This asymmetry decreases at hatching and disappears at stage 34. In the tectum, the proliferative zone is periventricular and lies along the medial, lateral and caudal rim. During ontogenesis, the lateral and caudal proliferative zones are moving back. The quantitative analysis of the retina, tectum and of their proliferative zones show that the volumes are highly correlated for all the specimens over the three stages. The volume variation is subordinate to the growth, low between stages 27 and 30, high between stages 30 and 34. Nevertheless the tectal proliferative zone exhibits a typical change: it decreases at hatching then increases at stage 34. At this stage the volume of the proliferative zones of the retina and tectum are discordant. The peculiar quantitative development of tectal proliferative zone predict the shifting of the retino-tectal projections and may be correlated with the timing of tectal developmental events. PMID- 2254659 TI - Growth of the hippocampal grafts in the rat anterior eye chamber: effects of age and strain of the recipients. AB - Hippocampal tissue (1 mm3) was taken from embryonal (E17-18) rats of Wistar stock in population breeding and grafted into anterior eye chamber of the four groups of recipients: young (3 weeks) and old (18 months) males of the same stock and of inbred strain WAG. Morphometric analysis of the grafts developing up to 12 weeks in oculo showed rapid initial growth in both groups of the young hosts during the first three weeks, and limited increase of the graft volume during next three weeks. The start of growth was significantly retarded in the old hosts, but this was partly compensated by prolonged increase of the graft volume during the later stages. Both mean and maximal finite volume were much smaller in both WAG groups. The hippocampal grafts in these groups had rounded (not elongated, as in Wistar groups) shape and showed tendency to fragmentation and resorbtion at the late stages. Histological analysis revealed well organized layer of the pyramidal cells in the both Wistar groups and nearly complete absence of neuronal organization into layer in both WAG groups. Possible role of trophic and immune factors in development of intraocular grafts is discussed. PMID- 2254660 TI - Cytochemical localization of calcium in the corpus Luysi of the rat after ischemia. AB - The postischemic ultrastructural localization of calcium in the corpus Luysi of the rat was investigated. We observed an increased calcium sequestration in mitochondria of some neurons and astrocytes in the post-ischemic period. Calcium precipitates were also present in Golgi vesicles, multivesicular bodies, synaptic vesicles, synaptic clefts and some channels of the smooth endoplasmic reticulum. These cellular organelles may be involved in the control of intracellular calcium exchange. Abundant Ca2+ precipitates were found in the cytoplasmic matrix of some neurons and astrocytes. Occasional neurons exhibited changes in cytoskeleton elements. Ultrastructural alterations in the myelin sheaths were noticed. Increased amounts of calcium were found between disjuncted myelin lamellae. The possible role of calcium in ischemic neuronal damage is briefly discussed. PMID- 2254661 TI - Different laminar distribution of flash evoked potentials in cortical areas 17 and 18 b of freely moving rats. AB - The laminar distribution of flash evoked field potential (VEP) was investigated in the visual cortical areas 17 and 18 b in freely moving rats. Averaged VEPs were recorded during stable relaxed wakefulness characterized behaviorally and polygraphically. The depth profiles of the main VEP components displayed polarity reversals in lamina V in every electrode track through area 17 while no polarity reversal was observed in any track through area 18 b. The primary negative component (N30) had an amplitude maximum in lamina IV in both areas. Current source-density analysis (CSD) in connection with amplitude depth profiles indicated that the surface-negative component N30 is generated mainly by the synaptic excitatory inputs in lamina IV. The negative peak of the flash-evoked afterdischarges in area 17 are generated the same way. The data imply a more concentrated field generator in area 17 with densely packed cellular elements responding synchronously to the flash. In area 18 b, either the anatomical distribution or the temporal relationship of the responding elements seems to be different. PMID- 2254662 TI - An electron immunocytochemical study of the basilar artery in rabbits after subarachnoid haemorrhage (SAH): a preliminary report. AB - Vascular endothelial cells of the basilar artery and secretory axons of the neurohypophysis from rabbits after experimental subarachnoid haemorrhage were investigated by postembedding peroxidase--anti-peroxidase technique for electron microscopy to detection of vasopressin (VP). The results indicate an lack of VP positive endothelial cells in basilar artery, while VP-positive secretory granules were commonly present in the neurohypophysis. The results are discussed in terms of pathophysiological aspect of subarachnoid haemorrhage. PMID- 2254663 TI - Crystalloid tubular arrays in sensory neurons after ischemia in the dog. AB - Crystalloid tubular arrays in the cytoplasm of canine sensory neurons were found after repeated 40 min aortic occlusion. The inclusions were composed of 35-40 nm tubules in parallel rows connected by fine side-arms. The tubular aggregates seem to be transient formations and were observed mostly in animals with 2-3 days of survival. After longer survival period (6 days) when signs of recovery in neurons were noticed, the crystalloids were not found. PMID- 2254664 TI - Particle counting immunoassay of choriogonadotropin using monoclonal antibodies. AB - A latex particle immunoassay has been developed for the quantification of choriogonadotropin in human serum using two monoclonal antibodies specific for the beta-chain of the hormone. The assay, based on optical counting of monomeric particles, was achieved in 40 min and the calibration curve was linear between 10 and 200 IU/l. Intra- and interassay precisions at three different levels of the curve varied between 3.3 and 10.9%. The method was validated by comparison with two different radioimmunoassays and correlation coefficients of 0.97-0.99 were obtained. PMID- 2254665 TI - Comparison of various methods for monitoring hybridoma cell proliferation. AB - The design of a strategy for the control of large scale cultures of hybridoma cells requires the use of convenient indicators to monitor properly the evolution of the biomass. In order to select appropriate indicators, we have measured in parallel, in bulk cultures of mouse hybridoma cells, the evolution of several metabolic parameters together with those of cell density and viability. We observed that flow cytometry analysis gives an early indication of the proliferative capacity of the cell population. Determination of metabolic rates (i.e. glucose, glutamine, amino acid, consumption, lactic acid or ammonium production) adequately indicates the current metabolic status of the cells. Indeed, a sharp decrease in these metabolic rates occurs rapidly following nutrient deficiency. Finally, measurements of lactate dehydrogenase (LDH) and DNA fragments released into the culture supernatants accurately reflect the kinetics of cell death. PMID- 2254666 TI - A new assay for cell death. AB - A new assay for the evaluation of cell viability is described. It is based on the staining of dead cells and subsequently the whole cell population with ethidium bromide (EtBr). The method makes it possible to measure cytotoxic and cytostatic effects simultaneously and cell cultures grown both in suspension as well as by adherence may be assessed. The advantages and disadvantages of this assay are discussed. PMID- 2254667 TI - Antibody-coated liposomes as a particulate solid phase for immunoassays. Measurement of urinary 'micro-albumin'. AB - A novel use of liposomes as a solid phase material achieving separation in immunoassays is described. Antibody-coated liposomes were prepared and used as a particulate solid phase in a radioimmunoassay procedure for urinary albumin. The assay was compared to a liquid phase albumin radioimmunoassay. The potential benefits of liposomes over other particulate solid phases are discussed. The use of liposomes in this manner need not be restricted to radioimmunoassay but should also be applicable to other immunoassays using alternative non-isotopic labels. PMID- 2254668 TI - The use of N-(aminobenzoyloxy) succinimide as a two-level heterobifunctional agent for the preparation of hapten-protein conjugates. Daunomycin as a model hapten with an amino group. AB - Three geometric ortho-, meta-, and para-isomers of N-(aminobenzoyloxy)succinimide (ABS) were synthesized, and their usefulness as a two-level heterobifunctional cross-linking agent in the preparation of hapten-protein conjugates was evaluated. The conjugation was based on the principle that ABS reacts immediately with an amino group of a hapten, and an aminobenzoyl group incorporated into the hapten is then activated by diazotization to a functional diazobenzoyl group acting on tyrosine or histidine residues of the protein. Using the anti-tumor antibiotic daunomycin (DM) as a model hapten, the three isomers of ABS were compared for their ability to conjugate DM with bovine serum albumin (BSA); DM incorporation onto a BSA molecular was found to occur to the highest degree with m-ABS, followed by p-ABS. while o-ABS completely failed to conjugate under the same coupling conditions. Using m-ABS it was possible to introduce more than 10 molecules of DM per BSA molecule. One of the DM-BSA samples was used as the immunogen for the production of anti-DM serum in a rabbit. The antibody specificity was shown to be direct to DM but not to other anti-cancer drugs (bleomycin, mitomycin C, actinomycin D and 5-fluorouracil) by the double antibody enzyme immunoassay (DEIA) using DM-beta-galactosidase conjugate as a label. An enzyme-linked immunosorbent assay (ELISA) for anti-DM IgG was developed using a DM-human serum albumin (DM-HSA) conjugate similarly prepared with m-ABS and horseradish peroxidase-conjugated goat anti-rabbit IgG as the solid-phase antigen and the labelled second antibody, respectively. This ELISA permitted us to measure accurately as little as 50 ng of anti-DM IgG per ml using a standard anti DM IgG which had been purified from the anti-DM serum using an affinity column of Sepharose 4B with DM-HSA as the ligand. Using this ELISA as well as a sandwich enzyme immunoassay (SEIA) for total IgG, serum levels of anti-DM IgG and total IgG levels were easily monitored in a rabbit following immunization with DM-BSA. These results indicate that the use of DBS provides a novel method for preparing hapten-protein conjugates which will be useful in biochemistry and immunochemistry. PMID- 2254669 TI - A new one-step method for the isolation of human mononuclear cells. AB - This paper describes a radical new, one-step method for the routine isolation of the mononuclear cells from human blood in high yield and purity. In this procedure the blood sample is mixed with a Nycodenz separation medium prior to centrifugation. Erythrocytes and polymorphogranulocytes are pelleted during centrifugation leaving the mononuclear cells in the supernatant. The method can be used for a wide range of blood sample volumes and can be carried out with greater ease than the currently accepted methods. PMID- 2254670 TI - A rapid and sensitive immunoassay for tumor necrosis factor using magnetic monodisperse polymer particles. AB - A sensitive and rapid immunoassay for the detection of tumor necrosis factor (TNF) has been developed. Magnetic monodisperse polymer particles (M-280 Dynabeads) used as solid phase material, were coated with a neutralizing mouse monoclonal antibody to TNF. The coated Dynabeads were shown to have a more rapid binding capacity for recombinant (r) TNF as compared to standard immunowells coated with antibodies to TNF. The amount of TNF bound to the Dynabeads was quantified using either a polyclonal antibody to TNF or a mouse monoclonal antibody to TNF. The antibodies used for detection were either labelled with 125I or peroxidase. The linear assay range for the TNF standard curve was form 62 to 4000 pg/ml, and the assay time was less than 60 min. The sensitivity could be increased 5-8-fold by increasing the sample volume from 0.1 to 2 ml. PMID- 2254671 TI - Immunoblotting techniques for the detection of low level homogeneous immunoglobulin components in serum. AB - Because of the increasing demand for simple and reliable techniques for the detection of low concentrations of paraproteins against a highly heterogeneous serum background, two techniques were investigated for their sensitivity: isoelectric focusing (IEF) and Wieme high resolution electrophoresis, each with subsequent blotting by diffusion. The techniques were compared using isolated mouse monoclonal antibodies (mAb) of known concentration and specificity. Wieme electrophoresis in combination with immunoblotting (IBL) or antigen-specific immunoblotting (ABL) has a detection limit of 100 ng/ml and 10 ng/ml, respectively. For IEF in combination with IBL or ABL these limits were 1000 and 30 ng/ml, respectively. For ABL, polyvinylidene difluoride (PVDF) and nylon supported nitrocellulose (NSNC) membranes gave similar detection limits, although for IBL, PVDF is preferred to NSNC. While IEF is essential for investigating the spectrum of the antibody repertoire. Wieme electrophoresis is the most powerful technique for the detection of homogeneous immunoglobulin components (H-Ig). After separation of the proteins. IBL is fast, simple and sensitive enough for routine detection and characterization of H-Ig. However, when the antibody specificity is known, ABL should be chosen for its superior sensitivity. PMID- 2254672 TI - Doxium 500 in chronic venous insufficiency: a double-blind placebo controlled multicentre study. AB - The aim of this double-blind placebo-controlled study was to evaluate the therapeutic efficacy of Doxium in chronic venous insufficiency (CVI). 225 patients were treated randomly for 4 weeks with 1.5 g (3 capsules/day) of Doxium or placebo. The evolution of the leg oedema was determined by measuring calf and ankle circumferences. Pain and discomfort were assessed by visual analogue scale. The results show that at the end of the trial, all the examined parameters (leg oedema, pain, day and night cramps, discomfort, heavy legs, paresthesia and restless legs) were significantly more improved in the Doxium group than in the placebo group: the leg volume was diminished by 3.8% in the Doxium group compared to 1.2% in the placebo (p less than 0.005). The overall assessment by the physicians showed an improvement in 82% of the Doxium-treated patients compared to 42% of the placebo group (p less than 0.0001). The tolerance of the treatment was comparable in both groups. PMID- 2254673 TI - The value of sigmoideoscopy in the diagnosis of ischemic colitis following aortic reconstruction. AB - During a 4 1/2-years period sigmoideoscopy was performed when patients developed diarrhea and/or unexpected low abdominal pain within the first days following aortic reconstruction. In our investigation rigid sigmoideoscopy, revealed all the cases of major ischemic colitis. PMID- 2254674 TI - Ketanserin in the treatment of diabetic foot ulcer with severe peripheral vascular disease. AB - The aim of this study was to evaluate if ketanserin, a selective serotoninantagonist, could improve wound healing in diabetic patients with foot ulcers and severe peripheral vascular disease. In a double blind study 40 diabetic patients with foot ulcer and a systolic toe pressure below 45 mmHg were randomly allocated to either ketanserin (20-40 mg three times a day) or placebo for a period of 3 months. The treatment was carried out on an out-patient basis by a combined medical/orthopedic foot care team at the Department of Internal Medicine, University Hospital, Lund, Sweden. Both groups were comparable regarding age, sex, duration and treatment of diabetes, cardiovascular disease and type of lesion. Wound healing (defined as intact skin for at least 3 months) or wound size reduction of 50% or more were sen in 11 out of 19 (58%) in the ketanserin group and in 7 out of 19 (37%) in the placebo group. Gangrene developed in 6 patients with placebo and 2 with ketanserin. Two patients died during the study and their ulcers were not evaluated. The systolic toe pressure was measured at admission, at end of run in, after 1 month and 3 months with strain gauge technique. Only one out of nine patients (11%) with a toe pressure below 30 mmHg in the placebo group healed or improved their ulcers compared to nine out of 16 (56%) in the ketanserin group. The healing rate in the ketanserin group was higher than expected considering the lower systolic toe pressure in this group compared to placebo at randomization (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254675 TI - Inflammatory aspects in atherosclerotic abdominal aortic aneurysms. A case report. AB - An important inflammatory reaction was histologically observed in the wall of an abdominal aortic aneurysm in a 42 year-old patient suffering from multifocal atherosclerotic lesions. Histochemical and ultrastructural studies showed an active-stage wall lymphomonoplasmacellular component. The histological appearance and biochemical and microbiological studies excluded specific aortitis, a rheumatic disease or concomitant infectious processes. The morphological relationships between the atherosclerotic lesion and the infiltrate together with the immunophenotyping features of the infiltrate suggest the possibility of a close correlation between the inflammatory process and the atherosclerotic lesion of the wall. PMID- 2254676 TI - Biogenesis and etiology of distal anastomotic intimal hyperplasia. AB - Distal anastomotic intimal hyperplasia (DAIH) is a viable biologic entity composed of a multi-interlamination of cells and extracellular matrix. Cell transformation and orientation characterize the dynamic process of this 80-130 cell structure. Morphologic similarity exists in the cytoarchitecture of DAIH irrespective of the graft material. Compliance mismatch is not a cause of DAIH, but it enhances the formation. The geometry of the unnatural distal end-to-side anastomosis is predisposed to turbulent flow and DAIH formation. Prevention of DAIH is dependent on pharmacologic suppression of subendothelial smooth muscle proliferation and synthesis of extracellular matrix. PMID- 2254677 TI - Lack of glutathione transferase activity in intermittent claudication. AB - Glutathione transferase activity towards trans-stilbene oxide (GT-tSBO), an enzyme involved in the detoxification of many substances such as polycyclic aromatic hydrocarbons, was studied in 77 consecutive patients operated with coronary bypass, 73 patients with intermittent claudication, 78 healthy smokers and in 38 healthy non-smokers. The mean ages of these groups were similar. Lack of GT-tSBO was recorded in 45% of coronary bypass patients, in 39% of smoking coronary bypass patients, in 61% of patients with intermittent claudication, in 41% of healthy smokers and in 31% of healthy non-smokers. The lack of GT-tSBO was significantly more frequent among patients with intermittent claudication compared to healthy non-smokers (p less than 0.01) and healthy smokers (p less than 0.025) and to smoking coronary bypass. It is concluded that the lack of GT tSBO is found more frequently among patients with intermittent claudication and this might contribute to explain the sensitivity to smoking among these subjects. PMID- 2254678 TI - A clinical trial of Gingkco Biloba Extract in patients with intermittent claudication. AB - Thirty-seven patients with stage 2 peripheral vascular disease were randomised to receive a six month course of Gingkco Biloba Extract (Tanakan) or matching placebo. Assessment, by claudication distance, A/B ratio, Doppler ankle pressure response to exercise together with recovery time, and a 10 cm analogue scale (LAS) estimation of maximal pain severity, was performed before treatment, and at 6, 12 and 24 weeks. LAS scores were significantly improved after 24 weeks in patients receiving EgB, but not placebo. Claudication distance was significantly increased by Egb. Although claudication distance also increased in the placebo group, this was not significant. A/B ratio and Doppler ankle responses to exercise did not show any significant change in either group at any time interval, nor did the post exercise recovery time. Gingkco Biloba Extract is a safe and effective method of improving walking distance and reducing pain severity in patients with intermittent claudication, although Doppler studies have failed to suggest any gross improvement in the perfusion of the ischaemic leg. PMID- 2254679 TI - Noninvasive detection of coronary artery disease in patients presenting with claudication. AB - ECG chest wall mapping with bicycle ergometry which can detect not only myocardial ischaemia but also individual coronary artery territories involved has been used to screen 100 consecutive patients presenting with claudication. Fifty three had a positive history and/or evidence of ischaemic heart disease on a resting ECG. The test was positive in 38, negative in 38 and inconclusive in 24, the latter because of inadequate heart rate response. In 11 out of 38 (29%) with a positive test there was no history or evidence of myocardial ischaemia on a conventional resting ECG. ECG changes suggestive of three vessel coronary disease were found in three, single vessel coronary disease in 16 and two vessel disease in 19. Of the latter, eight had changes in the LAD/circumflex distribution, indicating left main stem or equivalent disease. These together with the three with triple vessel coronary disease constituted a subset of 11 (11%) high risk patients who merited coronary angiography with a view to confirming the presence of severe coronary disease. PMID- 2254680 TI - Vascular and humoral sympathetic nervous system reactivity during mental arithmetic in primary Raynaud's phenomenon. AB - To investigate the hypothesis of a sympathetic imbalance in the pathophysiology of digital vasospasms during stress we measured vascular and sympathetic nervous system reactivity during a standardized mental arithmetic test in 12 patients with primary Raynaud's phenomenon in comparison to 12 healthy control subjects. Blood pressure, heart rate, forearm blood flow and fingertip laser Doppler flux were measured together with the venous concentrations of norepinephrine and epinephrine from the back of the hand before and during mental arithmetic in a climate room. No significant differences in circulatory or sympathetic reactivity were found between both groups except for fingertip skin circulation with a small decrease of laser Doppler flux (-11.6%) in controls, whereas it increased in PRP (46.6%; p less than 0.05 between both groups). Baseline skin blood flow was inversely correlated with changes in laser Doppler flux (R = -0.91; p less than 0.001; no. 24) irrespective of the diagnosis when baseline skin bloodflow is low a vasodilatory response occurs and when it is high a vasoconstrictive response is seen. Initial laser Doppler flux was lower while baseline diastolic blood pressure, heart rate and (nor)epinephrine concentrations were significantly higher in Raynaud-patients suggesting an increased sympathetic activity at rest in primary Raynaud's phenomenon. PMID- 2254681 TI - New concepts in the management of ischaemic lower extremities. AB - Experience with a new operative procedure namely arterialization of popliteal vein (APV) on 182 cases with 80% success for ischaemic lower extremity due to chronic nonspecific arterial occlusive diseases (ChNAOD) not responding to conservative methods of management currently in vogue is described. Success of this new operation saves the limbs from amputation which was done when conservative methods failed. The main purpose of this article is to write about etiology-clinical features--laboratory--and angiographic findings of this ChNAOD and APV operation. Accidental discovery of gastrocnemious muscle circulation responsible for success of APV operation is mentioned. PMID- 2254682 TI - Zona drilling: a new approach to male infertility. PMID- 2254683 TI - Assessment of hamster blastocysts derived from eight-cell embryos cultured in hamster embryo culture medium-2 (HECM-2): cell numbers and viability following embryo transfer. AB - The viability of hamster blastocysts, cultured from the eight-cell stage using hamster embryo culture medium-2, was examined by embryo transfer. Approximately 15-20 cultured hamster blastocysts were surgically transferred unilaterally to uterine horns of pseudopregnant recipient hamsters that had been mated to vasectomized males 3 days previously. Control recipients received in vivo developed, freshly recovered eight-cell embryos or blastocysts on day 2 or 3 of pseudopregnancy, respectively. Of the successful embryo transfers, the experimental group (receiving cultured blastocyts; n = 10) gave 51.8% implantations and 28.2% live pups. These values were closely similar to those of the controls; the percentages of control implantations and offspring were 51.1 and 34.0%, respectively, for eight-cell embryo transfer (n = 7, P greater than 0.69) and 48.5 and 28.9% for blastocyst transfer (n = 6, P greater than 0.52). To evaluate the quality of cultured hamster blastocysts, the following two parameters were examined. (1) The mean number of cells per blastocyst was 24.4 +/ 0.7 for cultured blastocysts. This value was similar to that (range, 14-24) obtained in this laboratory for in vivo developed freshly recovered blastocysts. (2) Oxygen consumption analysis revealed that cultured blastocysts actively respired at a level close to that observed with freshly recovered eight-cell embryos (slopes of oxygrams: 0.25 and 0.26, respectively). From these results, it is concluded that hamster blastocysts, cultured from the eight-cell stage, are (a) qualitatively similar to freshly recovered in vivo developed blastocysts and (b) biologically viable as revealed by the production of live offspring upon embryo transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254684 TI - Data base management system for assisted reproduction. AB - A substantial amount of data are generated from a single cycle of in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or related techniques. Maintaining an accurate and timely record of the flow of information is complicated by provision of service to many patients concurrently, diverse origins of data, and the use of donor sperm, donor oocytes, and/or cryopreservation. We have developed a data base management system for use on a network of personal computers that takes into account the volume, intricacy, and specialized features of data generated by IVF and GIFT programs. The major products of the system are (1) compact, individual patient reports on virtually all details of each treatment cycle; (2) reports on aggregate data (e.g., monthly, quarterly, or yearly); (3) automated summaries for submission to the American Fertility Society National Registry; and (4) creation of raw data files of user-specified variables that could be used for statistical analysis. PMID- 2254685 TI - Ovarian response to exogenous gonadotropins during pregnancy. AB - Multiple ovarian follicles were successfully induced in a patient undergoing superovulation for a gamete intrafallopian transfer (GIFT) procedure despite the presence of an undiagnosed ectopic pregnancy. Midluteal gonadotropin releasing hormone agonist (GnRH-a) treatment should be coupled with mechanical contraception in the previous cycle in patients with patent tubes. PMID- 2254686 TI - The establishment of an ovum donation program using a simple fixed-dose estrogen progesterone replacement regimen. AB - Most ovum donation (OD) programs involve cycle synchronization between recipient and donor for normally cycling recipients and a complex estrogen-progesterone replacement regimen for recipients with ovarian failure. In 1987, Serhal and Craft (1) suggested the use of a fixed-dose estrogen-progesterone regimen for recipients who were normally ovulatory and to those with ovarian failure. Following this protocol, and simplifying it still, the authors administered 6 mg estradiol valerate (E2) daily orally starting on day 2-6 of induced withdrawal bleeding, augmented with 100 mg progesterone in ethyl oleate (P) intramuscularly daily, starting any time between 4 days prior to and the day of oocyte pickup. All recipients underwent embryo transfer at a 2-pronuclei (2PN)-10-cell stage. A group of 21 patients underwent 26 treatment cycles, resulting in 16 pregnancies. Twelve of the patients gave birth, one to triplets, two to twins, and nine to singletons. Four patients miscarried in the first trimester of pregnancy. PMID- 2254687 TI - A microcomputer data base system for an in vitro fertilization clinic programmed in BASIC. AB - A computer program was developed for the IBM personal computer to be used for in vitro fertilization and gamete intrafallopian transfer clinics. This program, written in BASIC, allows input, editing, updating, sorting, and printing of patient data. Statistical functions permit summation of patient data based on various combinations of user-defined treatment cycles, diagnoses, and protocols, thus making possible comparison of pregnancy and other patient data between and among various treatment groups and diagnoses. The statistical information can be continually updated and revised when new data become available on patients (such as confirmation of pregnancy by ultrasound or live births) and at the end of each cycle. The formats used are useful in assimilating individual clinic data for various surveys and other reporting requirements. The program can be easily modified by anyone with minimal training in the BASIC programming language. PMID- 2254688 TI - The prevalence of human immunodeficiency virus in patients and their spouses entering a large in vitro fertilization program. AB - Between September 1987 and August 1989, all patients and their spouses entering our in vitro fertilization (IVF) program were screened for the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA). Of 848 patients and 848 spouses tested, all but 4 patients and 1 husband tested negative. Of those who tested positive on repeat testing with ELISA, only one was positive on Western blotting (HIV prevalence, 0.59 per 1000). During this same time period 1187 samples of human cord blood were used to make tissue culture medium for the IVF embryology laboratory. One sample was discarded because of positive HIV on ELISA and Western blotting; two other samples were discarded because of positivity to the hepatitis B surface antigen. While we believe that routine HIV screening of IVF patients and their spouses is indicated, this population is of low risk for HIV positivity. Furthermore, continued screening of human sera used to make tissue culture media for IVF is mandatory. PMID- 2254689 TI - The impact of embryo quality on pregnancy outcome in elderly women undergoing in vitro fertilization-embryo transfer (IVF-ET). AB - Most IVF-ET units limit the procedure to women below age 38. Nevertheless, demands for infertility treatment, including IVF therapy, are more frequent nowadays. We compared 46 cycles for ovulation induction for IVF in 46 women aged 40 or more (Group I) to 51 induced cycles for this procedure in younger women of mean age 30.2 years (Group II). Cancellation rates due to early luteinization or ovulation were significantly higher in group I than in group II (28.2 and 17.6%, respectively) (P less than 0.001). Also, significantly higher abortion rates were observed in older women (62.5%), in comparison to the younger control group, (25%), (P less than 0.001). It is suggested that the high abortion rate considered to be due to genetic factors in older women, may possibly also be due to the aging uterine environment. Furthermore, while embryos with fragmentations may often produce clinical pregnancies in the young, the aging uterus in the elderly woman does not encourage the development of clinical pregnancies in such embryos. Consequently the higher abortion rate in the elderly woman. PMID- 2254690 TI - Successful ultrarapid freezing of unfertilized oocytes. AB - Successful application of ultrarapid freezing techniques to unfertilized murine oocytes has not been reported. In an effort to improve results, preovulatory murine oocytes were exposed to three ultrarapid freezing protocols involving varying sucrose concentrations (0.25, 0.5, and 1.0 M) and 3.5 M dimethyl sulfoxide (DMSO) as cryoprotectants prior to direct immersion in liquid nitrogen. Post-thaw morphology and rates of in vitro fertilization and embryo development were compared with those obtained after freezing oocytes employing two established programmed cooling techniques. The rates of fertilization and development to the blastocyst stage in vitro of oocytes undergoing ultrarapid freezing after exposure to 3.5 M DMSO and 0.5 M sucrose were similar or superior to those obtained with programmed cooling techniques. Of oocytes which appeared morphologically normal post-thaw, only those which underwent ultrarapid freezing with 0.25 or 0.5 M sucrose and 3.5 M DMSO reached the blastocyst stage at rates similar to those of controls. Ultrarapid freezing may represent a viable option for successful murine oocyte cryopreservation. PMID- 2254691 TI - The value of hysteroscopy in elderly women prior to in vitro fertilization-embryo transfer (IVF-ET): a comparative study. AB - Two hundred eighty-four hysteroscopies were performed in 312 (91%) candidates for in vitro fertilization and embryo transfer (IVF-ET) who were divided into two groups. Group I consisted of elderly women over 40 years, and group II of women below this age. Although visualization revealed uterine abnormalities in 29.9% of all patients, abnormal findings were significantly increased in the former group in comparison to the latter (P less than 0.001). This difference was attributed mainly to uterine rather than cervical pathology. Furthermore, in elderly women age-related uterine pathology such as submucous myomata, endometrial hyperplasia, and polyps were more prominent, while in younger patients other uterine lesions such as adhesions and tubal ostia occlusion were more common. Moreover, treatment prior to IVF-ET resulted in 7 clinical pregnancies (8.9%) in group I and in 41 clinical pregnancies (19.9%) in group II, all of which failed in one to three cycles previously. It seems that hysteroscopic evaluation may reduce the IVF-ET failure rate due to intrauterine abnormalities in elderly as well as young patients, thus it becomes an absolute prerequisite for all patients scheduled for an IVF program. PMID- 2254692 TI - Preimplantation murine embryos are more resistant than human embryos to bacterial endotoxins. AB - Bacterial endotoxins have been correlated with increased fragmentation of early cleavage-stage human embryos and decreased pregnancy rates in human in vitro fertilization programs. The purpose of the present study was to test the direct effects of increasing concentrations of endotoxins on in vitro fertilization and development of mouse embryos to the blastocyst stage. Sexually mature B6D2F1 female mice were superovulated and oocytecumulus complexes were collected from the oviducts and randomized into control and treatment groups. Oocytes (n = 867) were inseminated with capacitated sperm. Treatments included Ham's F-10 supplemented with 3 mg/ml bovine serum albumin and increasing amounts of endotoxin (0.35, 0.64, 0.92, 1.5, 2.08, 3.21, 6.07, and 11.79 ng/ml). Percentage cleavage, percentage fragmentation at the four-cell stage, and percentage expanded blastocyst formation (of cleaved embryos) were evaluated. Statistically significant decreases in cleavage at 6.07 ng/ml (P less than 0.05) and blastocyst formation at 11.79 ng/ml (P less than 0.05) of endotoxin were observed. Fragmentation at the four-cell stage was significantly increased at 3.21 ng/ml (P less than 0.05) of endotoxin. We conclude that the levels of endotoxin necessary to decrease murine preimplantation development significantly is higher than that reported for human embryos. PMID- 2254693 TI - Gamete intrafallopian transfer (GIFT) in women with bicornuate uteri. AB - Fourteen women with bicornuate uteri underwent a total of 30 gamete intrafallopian transfer procedures. All patients responded adequately to ovarian stimulation. Eight women conceived, two of them twice. Five women delivered at term and three had a premature delivery. There was one spontaneous abortion and an ectopic pregnancy. No neonatal deaths occurred in this series. No increase in the incidence of spontaneous abortion was noted but there appeared to be an increase in the incidence of premature labor. These findings suggest that the prospects of conception for infertile women with bicornuate uteri treated with gamete intrafallopian transfer are similar to those of the rest of the infertile population treated at our center. PMID- 2254694 TI - What's in a name? PMID- 2254695 TI - The Ljubljana IVF-ET program--brief report. PMID- 2254696 TI - Clinical results of the IVF Australia Program at United Hospital, Port Chester, New York. PMID- 2254697 TI - Combined monolateral replacement of gametes and eggs followed by delayed intrauterine insemination. PMID- 2254698 TI - An off-line digital system for reproducible interpretation of the exercise ECG. AB - Exercise electrocardiograms of 20 patients were analyzed using a customized software exercise electrocardiographic program and compared to measurements made by two cardiologists performing independent interpretations. The computerized program requires identification of the PQ junction, J point, and tracing of the ST-segment in three consecutive beats. The proportion of variance for J point, and ST 80 measurements was 0.93 and 0.90, respectively, when the same electrocardiogram was processed twice and analyzed by two separate cardiologists. The same 20 exercise electrocardiograms were analyzed by two other experienced cardiologists without computerized measurements. The proportion of variance was less at 0.73 and 0.76 for the J point and ST 80 measurements, respectively. The average amount of time required for the cardiologist to over read the computerized measurements was 2.7 +/- 1.5 minutes per ECG as compared to 20.7 +/- 11 minutes for the cardiologists who did not have computer-assisted measurements (p less than 0.0001). Thus, off-line computerized exercise electrocardiographic interpretation is highly reproducible, accurate, time-sparing for cardiologist over read function, and suitable for use in large-scale clinical trials. PMID- 2254699 TI - QRS onset and offset detection accuracy improvement by additional spatial information in body surface potential maps. AB - A new automatic spatiotemporal algorithm has been developed for detecting QRS onset and offset in body surface potential mapping. The new algorithm, based on a spatial and temporal approach, along with three other algorithms (total energy, 3 lead, and median), was tested in 73 normal and abnormal patients. The reference or gold standard onset and offset times were determined visually by two experienced investigators. The results demonstrate that the new method is less sensitive to noise, to the temporal overlap of the QRS and other components, and to the spatial location changes of QRS initial and final activation. The spatiotemporal method resulted in very consistent findings, with a standard deviation of less than one third of the standard deviation in the next best method. PMID- 2254700 TI - Accuracy in clinical arrhythmia detection of a real-time Holter system (Oxford Medilog 4500). AB - The accuracy of a real-time analysis Holter system (Oxford Medilog 4500) in detecting ventricular and supraventricular arrhythmias was evaluated. Hand counted data from randomly selected hours of 152 ECG monitorings of 152 patients were used as the control standard. Accuracy of the system was evaluated on 606 hours for premature ventricular complexes (PVC), PVC couplets and supraventricular extrasystoles (SVE), and on 1,789 hours for ventricular tachycardia (VT), accelerated idioventricular rhythm (AIVR), and supraventricular tachycardia (SVT). Sensitivity and positive predictive accuracy for the Oxford system were (1) 92.9% and 94.9% for PVC; (2) 90.1% and 87.8% for PVC couplets; (3) 98.1% and 56% for AIVR; (4) 80% and 82.3% for VT; (5) 88.6% and 56.5% for SVE, and (6) 43.7% and 60.2% for SVT. Furthermore, negative predictive accuracy, the ability to predict the total absence of an arrhythmic event in an hour, was determined. It was 91.7% for PVC, 99.5% for PVC couplets, 99.9% for AIVR, 99.7% for VT, 95% for SVE, and 98% for SVT. ventricular arrhythmias, whereas significant inaccuracies appear to exist in the analysis of supraventricular arrhythmias. PMID- 2254701 TI - Abnormalities of early depolarization in patients with remote anterior myocardial infarction and ventricular septal hypoperfusion. Diagnosis of septal MI by BSM. AB - The authors conducted this study to find the difference in body surface isopotential maps in 46 patients with previous anterior infarction with and without septal involvement. Thallium-201 myocardial-perfusion imaging identified 25 patients with septal infarction (group P) and 21 without (group N). In contrast to group N, group P had a prominent minimum on the anterior chest during the early phases of the QRS. According to the results obtained, the following criteria for identifying patients with septal infarction (group P) were proposed (1). Criterion 1: The absolute value of the voltage of the minimum is equal to or greater than that of the maximum at 5 ms after the onset of the QRS; (2) Criterion 2: During the early portion of the QRS the voltage of the minimum reaches -0.10 mV at the same time or earlier than the maximum reaches 0.10 mV. Both criteria had higher sensitivities (100% and 100%), specificities (71.4% and 90.5%), and predictive accuracies (87.0% and 95.7%) than either Franklead vectorcardiograms or standard 12-lead electrocardiograms in the study population. Thus, body surface isopotential mapping is considered to be useful for the diagnosis of septal involvement in patients with previous anterior myocardial infarction. PMID- 2254702 TI - Complementary nature of electrocardiographic and magnetocardiographic data in patients with ischemic heart disease. AB - High resolution body surface potential maps (BSPM) and magnetic field maps (MFM) for study groups consisting of 11 Q wave and 11 non Q wave myocardial infarct (MI) patients as well as 9 normal subjects, were recorded in a magnetically and electrically shielded room. A control group of 22 normal subjects provided group mean normal time integral maps for selected QRST time intervals. The difference between magnitudes of extrema in each map defined the normal mean data range R for that time interval. The root mean square sum of the differences between the time integral map of a study subject and the normal group-mean map provided an estimate of individual map variability, V. Subsequent calculation of group-mean map variability, V, and group-mean normalized variability, V/R, for specific time intervals of the cardiac cycle, were used to test the abilities of BSPM and MFM techniques to distinguish between the normal and MI study groups. Results indicate that BSPM V/R differences between MI and normal groups are most pronounced during Q wave and Q zone activity; between inferior MI's and normals (p less than 0.05) and between anterior MI's and normal (p less than 0.01). Significant differences in MFM V/R occur during repolarization; between inferior MI's and non Q wave MI's (p less than 0.05), between anterior MI's and normals (p less than 0.05), between non Q wave MI's and normals (p less than 0.05) and between all MI's and normals (p less than 0.01). It is concluded that high resolution BSPM and MFM provide complementary means of discriminating between normal subjects and MI patients. PMID- 2254703 TI - Vector U loop in patients with idiopathic cardiomyopathy. AB - The U loops of vectorcardiograms were recorded in 50 normal subjects, 10 patients with dilated cardiomyopathy (DCM group), and 83 patients with hypertrophic cardiomyopathy (HCM group). The HCM group was divided into three subgroups: those with obstructive hypertrophic cardiomyopathy (HOCM), nonobstructive hypertrophic cardiomyopathy (HNCM), and apical hypertrophy (APH). The spatial characteristics of the U loop were examined qualitatively and quantitatively and were correlated with echocardiographic findings. The magnitude of the U loop was significantly larger in the HCM group, especially in the APH subgroup, than in the normal subjects, but it was not larger in the DCM group. The maximum U vector was significantly displaced anteriorly and to the right in the DCM and HCM groups, especially the APH and HNCM subgroups. In the HNCM and APH subgroups, the magnitude of the U loop correlated significantly with the thickness of the posterior wall of the left ventricle, but not with that of the interventricular septum. These findings suggest that the U loop is related to hypertrophy of the apex and the posterior wall of the left ventricle. PMID- 2254704 TI - Reversal of low voltage and infarction pattern on the surface electrocardiogram after renal hemodialysis for pulmonary edema. AB - A case is presented in which markedly low surface electrocardiographic (ECG) voltage and an infarction pattern are rapidly reversed with renal hemodialysis for pulmonary edema. A patient presenting with QRS voltages below 0.1 mV in all the limb and augmented limb leads and a waveform pattern suggestive of an anterior and inferior myocardial infarction experienced a dramatic increase in voltage and a reversal of the infarction pattern after dialysis. A hypothesis is proposed in which alterations in chest wall impedance and in electrolytes are involved in the ECG changes resulting from dialysis. This case illustrates one source of diagnostic error, and that dialysis may result in large, rapid changes in the ECG. Diagnostic errors may be avoided by obtaining serial ECGs in patients undergoing dialysis. PMID- 2254705 TI - Ventricular fibrillation during partial reperfusion following severe myocardial ischemia in the canine model. AB - The authors examined whether partial reperfusion protects against reperfusion ventricular fibrillation (VF) following severe acute myocardial ischemia. Fifty seven dogs were divided into two groups. In group A (n = 21), the left anterior descending coronary artery was occluded for 10 minutes, followed by full reperfusion. In the remaining 36 dogs (group B), myocardial ischemia was induced by retrograde blood flow (RBF) for 10 minutes. Thereafter, these dogs were divided into three subgroups: in group B1 (n = 10), full reperfusion was made by a carotid-left anterior descending coronary artery bypass; in group B2 (n = 13), partial reperfusion was achieved by collateral flow into the ischemic zone due to stopping RBF; in group B3 (n = 13), RBF was continued for an additional 5 minutes. During 10 minute ischemia, the myocardial blood flow at the ischemic zone measured by the H2 gas-clearance method was 12.3 +/- 2.0 ml/min/100 g in A, 3.4 +/- 0.9 ml/min/100 g in B1, 4.7 +/- 0.6 ml/min/100 g in B2, and 4.7 +/- 0.6 ml/min/100 g in B3 (A vs B1, p less than 0.02; A vs B2 and B3, p less than 0.01). Maximal ST-segment elevation was 11.4 +/- 1.8 mV in A, 28.2 +/- 2.7 mV in B1, 25.1 +/- 3.0 mV in B2, and 27.0 +/- 1.9 mV in B3 (A vs B1, B2, and B3, p less than 0.001). Maximal conduction delay was 48.6 +/- 9.4 ms in A, 106.4 +/- 5.2 ms in B1, 101.6 +/- 9.9 ms in B2, and 91.2 +/- 5.1 ms in B3 (A vs B1, B2, and B3, p less than 0.001). The incidence of reperfusion VF was 14% (3/21) in A, 80% (8/10) in B1, and 69% (9/13) in B2 (A vs B1, p less than 0.001; A vs B2, p less than 0.005). In group B3, VF occurred in only 1 of 13 dogs for the additional 5 minutes. It is concluded that reperfusion VF occurred frequently when ischemia was severe even though the duration of ischemia was short (B1), and that reperfusion VF was not prevented by partial reperfusion when the ischemia was severe (B2). PMID- 2254706 TI - Routine electrocardiograms after cardiac catheterization. Are they useful? AB - In order to assess the value of routine electrocardiograms after cardiac catheterization (ECGs), 150 consecutive patients undergoing diagnostic cardiac catheterization were studied prospectively. The physician performing each catheterization was asked to rate his or her clinical index of suspicion that the electrocardiogram would be changed as a result of events during the procedure. Clinical index of suspicion and electrocardiograms were then compared for their ability to predict outcomes. Urgent clinical events within 24 hours of cardiac catheterization were defined as (1) new intensive care unit admission; (2) myocardial infarction; (3) coronary artery bypass graft surgery; (4) percutaneous transluminal coronary angioplasty; or (5) death. Chi square analysis demonstrated that neither ECGs (x2 = 2.12, p greater than 0.1) nor clinical index of suspicion (x2 = 2.43, p greater than 0.1) was better than chance alone in predicting urgent clinical events. The addition of ECGs to positive clinical index of suspicion did not increase the ability to predict urgent clinical events (x2 = 2.38, p greater than 0.1). Both ECGs and clinical index of suspicion were found to be relatively insensitive tests (sensitivity = 29% for ECGs, 43% for clinical index of suspicion). While both tests demonstrated high specificity, (89% for ECGs, 79% for clinical index of suspicion), their predictive value was equally poor (21% for ECGs, 17% for clinical index of suspicion). The addition of ECGs to clinical index of suspicion marginally increased the sensitivity of both tests to 50%. We conclude that routine postcatheterization electrocardiograms are no better at predicting urgent clinical events than clinical observation during catheterization alone, and should be performed only when index of suspicion dictates. PMID- 2254707 TI - Complete atrioventricular block with QRS complexes of variable amplitude. AB - Nonrespiratory QRS amplitude variations related to PR interval length were observed in a case of complete atrioventricular (AV) block with narrow QRS complexes. This electrocardiographic pattern was studied, taking into consideration the greater deflection of the ventricular complexes (R- or S-wave) on each standard lead and by analyzing three groups of QRS (A, B, C) divided in relation to the different timing of the atrial systole. A significant variation appears in the entity of the mitral flow, as assessed by Doppler echocardiography evaluation, related to PR interval length, and a significant inverse correlation was found between QRS variability and ventricular diastolic filling. PMID- 2254708 TI - An ECG marker of underlying right ventricular conduction delay in the hyperacute phase of right ventricular infarction or ischemia. AB - Patients with extensive right ventricular (RV) infarction or ischemia often have an accompanying RV conduction delay. Such patients frequently show precordial ST T wave elevation, which hides the late r' wave in lead V1, making it difficult to recognize the RV conduction delay during the hyperacute phase. We noted that such patients occasionally exhibited a "cove"-shaped ST-T elevation in lead V1, which strongly suggested the presence of this complication even in the hyperacute stage. This report describes three instances of RV infarction or ischemia with this characteristic electrocardiographic sign. This sign appears to be a marker of RV conduction delay during the hyperacute stage of RV infarction or ischemia. PMID- 2254709 TI - Coronary heart disease in the absence of hypercholesterolaemia. PMID- 2254710 TI - Disease, race, geography and genes. PMID- 2254711 TI - Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia. AB - Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment. PMID- 2254712 TI - Parasympathetic nervous system activity in hypothyroidism determined by R-R interval variations on electrocardiogram. AB - Little is known about the relationship between hypothyroidism and the parasympathetic nervous system. R-R interval variations revealed by electrocardiogram (ECG) are known to be a useful clinical indicator of abnormalities of parasympathetic nervous system activity. Studies were conducted in hypothyroid patients, and significant reductions in R-R interval variations were observed in patients with primary severe hypothyroidism due to Hashimoto's thyroiditis, and in patients with Graves' disease who became severely hypothyroid during antithyroid drug therapy. R-R interval variations were restored to normal levels in both groups of patients after treatment. The present investigation suggests that in marked hypothyroidism there are hypofunctional abnormalities in the parasympathetic nervous system in association with a reduction in the levels of serum T4 and T3. PMID- 2254713 TI - Are blood pressure levels increasing in Denmark? AB - The Copenhagen City Heart Study is a prospective cardiovascular population study designed to evaluate the incidence of and risk factors for cardiovascular disease. A random population sample comprising approximately 20,000 individuals was invited to participate. Blood pressure was measured, and information regarding the use of antihypertensive medication was collected in an initial survey during the period 1976-1978 (attendance rate 74%) and from a second survey during the period 1981-1983 (attendance rate 70%). A significant increase in systolic and diastolic blood pressure between survey 1 and survey 2 was found among both men and women greater than 40 years of age and not using antihypertensive medication. The increase in blood pressure in the follow-up survey could not be explained by changes in methods, changes in the prescription of antihypertensive medication, or selection bias. Factors associated with changes in systolic and diastolic blood pressure were examined by multiple linear regression analysis. Both increase in body mass index and increase in alcohol consumption were positively correlated with changes in systolic and diastolic blood pressure, while use of antihypertensive medication, a high value of body mass index at survey 1 and a high level of education were negatively correlated with changes in systolic and diastolic blood pressure. Female sex and advanced age were also negatively correlated with changes in diastolic blood pressure. Consumption of tobacco and alcohol, income and changes in consumption of tobacco were not significantly correlated with changes in systolic and diastolic blood pressure. PMID- 2254714 TI - A randomized trial of the effect of three non-steroid anti-inflammatory agents in ameliorating cancer-induced fever. AB - Paraneoplastic fever is well known, and is not an uncommon problem in daily practice. In an effort to ameliorate tumour-induced fever we randomized 48 patients to receive three different non-steroid anti-inflammatory drugs: Naproxen (500 mg d-1), Indomethacin (75 mg d-1) or Diclophenac sodium (75 mg d-1). All patients had solid tumours, and microbial infection had been excluded. All three drugs were equally effective in bringing the temperature down to normal for a period of 30-33 d. Naproxen had the most rapid effect. In cases of fever relapse with the first drug, when the other two drugs were given instead, both proved equally effective. No side-effects were observed. We conclude that Naproxen, Indomethacin and Diclophenac sodium are equally effective in ameliorating paraneoplastic fever. In relapse, a second drug given subsequently can be effective as well. PMID- 2254715 TI - Continuous subcutaneous insulin infusion (CSII), multiple injections (MI) and conventional insulin therapy (CT) in self-selecting insulin-dependent diabetic patients. A comparison of metabolic control, acute complications and patient preferences. AB - Continuous subcutaneous insulin infusion (CSII) and multiple injections (MI) have been shown to have metabolic advantages in highly-selected insulin-dependent diabetics (IDDs), but there have been few comparative studies in self-selected IDDs. With MI, the optimal insulin preparation for overnight insulin delivery has not been defined. We compared conventional 2-3 injection therapy (CT), CSII and MI with human isophane insulin (MI/human isophane) and human ultralente insulin (MI/human ultralente), respectively, at bedtime in self-selected IDDs. Of 275 IDDs who were invited to participate, 52 individuals (18.9%) entered the study. Most indices of glycaemic control showed better values on CSII and also on MI compared to CT, but the differences were small. Fasting blood glucose was higher on MI/human ultralente than on MI/human isophane. Only one subcutaneous abscess and one case of ketoacidosis requiring hospitalization occurred on CSII. Serious hypoglycaemic episodes were non-significantly increased on intensified therapy. Most patients clearly preferred intensified insulin therapy; approximately one half CSII. PMID- 2254716 TI - Diagnostic applicability of intact and midregion/C-terminal parathyroid hormone assays in calcium metabolic disorders. AB - We compared measurements of parathyroid hormone (PTH) using two assays, in order to detect intact PTH and midregion/C-terminal PTH (M/C-PTH) in a variety of calcium metabolic disorders. The series consisted of a total of 101 patients, including subjects with primary hyperparathyroidism (n = 24), hypoparathyroidism (n = 18), hypercalcaemia of malignancy (n = 10), moderate chronic renal failure (n = 14), chronic renal failure undergoing haemodialysis (n = 19), and small bowel disorders (n = 16). The intact PTH assay was superior to the M/C-PTH assay in reflecting parathyroid function in primary hyperparathyroidism, hypoparathyroidism and hypercalcaemia of malignancy. In patients with chronic renal failure, both assays were indicators of a comparable number of patients with elevated PTH levels. Intact PTH proved most reliable in detecting changes in parathyroid hormone secretion in response to variations in ionized calcium induced by haemodialysis. In patients with extensive intestinal resection, both assays showed increased levels of PTH. It is concluded that measurement of intact PTH is a more reliable index of parathyroid function than measurement of midregion/C-terminal PTH. Thus such an approach should be the one of choice for clinical evaluation of calcium homeostasis. PMID- 2254717 TI - Coronary artery disease in Chinese males without hypercholesterolaemia. AB - The aim of this study was to determine the frequency of various metabolic risk factors for coronary artery disease (CAD) in 246 male patients studied over a 2 year period. CAD was diagnosed on the basis of a history indicative of angina pectoris, an electrocardiogram diagnostic of myocardial ischaemia, and a positive coronary angiogram. Thirty-eight per cent of this population had diabetes, hypertension or both. Of the remaining individuals, 39% had a plasma cholesterol concentration greater than 5.2 mmol l-1, whereas 23% had a cholesterol concentration less than 5.2 mmol l-1. Plasma lipid and lipoprotein levels of a non-smoking subset of those subjects with a total cholesterol concentration less than 5.2 mmol l-1 were compared with values of a matched group of individuals who did not have significant vessel disease as revealed by angiography. The results of these investigations indicated that patients with CAD and a plasma cholesterol concentration less than 5.2 mmol l-1 exhibited an increase in plasma triglyceride concentration and a decrease in plasma HDL-cholesterol concentration. Since these subjects were not diabetic, hypertensive or hypercholesterolaemic, it is suggested that the observed changes in triglyceride and HDL metabolism made a major contribution to the CAD in these individuals. PMID- 2254718 TI - Milk: does it affect blood pressure? A controlled intervention study. AB - In a double-blind trial, the effect on blood pressure of supplementation of normal milk (1180 mg Ca2+, 1650 mg K+ and 110 mg Mg2+ d-1) vs. 'mineral-poor' milk (95 mg Ca2+, 580 mg K+ and 10 mg Mg2+ d-1) was studied. Young healthy normotensive female students consumed one of the two supplements while on a low calcium diet (less than 500 mg Ca2+ d-1) for a period of 6 weeks. In both the normal milk- and 'mineral-poor' milk-supplemented groups systolic blood pressure decreased slightly. However, this decrease was persistently greater in the milk supplemented group. The individual mean systolic blood pressure change during normal milk treatment (-4.1%) was significantly greater (P = 0.03) than that during 'mineral-poor' milk treatment (-1.3%). An effect of normal milk supplementation on diastolic blood pressure could not be demonstrated. The results of the present study indicate a small hypotensive effect of milk consumption, which is attributable to its content of essential minerals. PMID- 2254719 TI - Ischaemic heart disease among men in Norway during the period 1966-1985: two counties with different mortality time trends. AB - We have examined regional differences in mortality from ischaemic heart disease, including sudden, unexpected death (IHD/SUD), among Norwegian men aged 30-69 years, during the period 1966-1985. Mortality time trends were considered. The two counties with the most widely differing IHD/SUD mortality time trends were Rogaland and Oppland. Rogaland, located in south-western Norway, experienced a 24.1% IHD/SUD mortality rate decrease between 1966-1970 and 1981-1985, while Oppland, in central south-eastern Norway, experienced a mortality rate increase of 12.4%. Marked regional differences within these counties were found. The highest IHD/SUD mortality rate increase occurred in rural areas of Oppland. Urban areas of Rogaland had sharply decreasing rates. Knowledge of such regional mortality differences could provide useful information regarding aetiological factors and serve as a basis for preventive measures and health-care planning. PMID- 2254720 TI - Elevation of skeletal muscle isoform of serum creatine kinase in heterozygous familial hypercholesterolaemia. AB - Serum creatine kinase (CK) is an important adjunct in the diagnosis of myocardial infarction or in monitoring for the side-effects of drugs. We report elevation of CK in patients with untreated heterozygous familial hypercholesterolaemia (FH) with no evidence of myocardial infarction. Of a group of 30 patients, 60% had elevated CK values on one occasion. In 40% of patients elevated CK activity was observed on most occasions. This was not related to exercise or previous lipid lowering therapy. These observations are of importance in view of the potential for misdiagnosis of myocardial infarction or premature withdrawal of lipid lowering therapy. PMID- 2254721 TI - Rebound increase in serum thyrotropin, anti-'microsomal' antibodies and thyroglobulin after discontinuation of L-thyroxine. AB - We assayed serum thyrotropin (TSH), antimicrosomal antibodies (MSA), antithyroglobulin antibodies and thyroglobulin in seven individuals with subclinical autoimmune hypothyroidism during two 6-month periods with L-thyroxine substitution and placebo, respectively. Serum TSH decreased during L-thyroxine administration, with a rebound increase in serum TSH of about 6 months duration during placebo treatment, and a parallel increase in serum thyroglobulin. In agreement with previous observations by other groups, we found decreased serum concentrations of MSA during L-thyroxine treatment in three individuals. In addition, a slow but significant transient increase in serum MSA was recorded during placebo administration in the four individuals who showed the most pronounced increase in serum TSH (greater than 20 mU l-1). This association between serum levels of MSA and TSH is most probably related to antigen presentation at the surface of the thyrocyte. We conclude that changes in serum TSH concentration should be taken into account in the interpretation of MSA in patients with thyroid disease, whether untreated or treated with L-thyroxine. PMID- 2254722 TI - Nisoldipine--effects on the renin-angiotensin-aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects. AB - We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels. PMID- 2254723 TI - Metabolic control and complications over 3 years in patients with insulin dependent diabetes (IDDM): the Stockholm Diabetes Intervention Study (SDIS). AB - In a planned 5-year study, 97 patients with insulin dependent diabetes mellitus (IDDM), non-proliferative retinopathy and unsatisfactory blood glucose control were monitored for 3 years. The patients were randomized to an intensified conventional treatment (ICT, n = 44) or a regular treatment (RT, n = 53) group. HbA1c (normal range 3.9-5.7%) was reduced from 9.5 +/- 0.2 (mean value +/- SEM) to 7.4 +/- 0.1% in the ICT group (P = 0.0001), and from 9.5 +/- 0.2 to 9.0 +/- 0.2% in the RT group (P = 0.004). Nerve conduction velocities in the sural and peroneal nerves (P = 0.01-0.0001) were impaired in the RT group, but not in the ICT group. Retinopathy increased in both groups. The condition of 22 ICT patients (50%, 95% confidence interval 34-66%) and 37 RT patients (73%, 61-84%) deteriorated with regard to at least one microvascular complication (retinopathy, nephropathy, neuropathy) (P = 0.024). Lower HbA1c levels during the study significantly reduced the risk of deterioration (P = 0.01). In total, 57% of the ICT patients had at least one episode of serious hypoglycaemia, compared with 23% in the RT group (P = 0.001). The patients in the ICT group also gained weight (P = 0.0001). Improved blood glucose control slowed down the progression of microangiopathy during a 3-year period in patients with non-proliferative retinopathy, but at the price of an increased frequency of serious hypoglycaemic episodes, and some gain in body weight. PMID- 2254724 TI - Components of delay time in suspected acute myocardial infarction with particular emphasis on patient delay. AB - Two hundred and thirty-four patients admitted to a coronary care unit (CCU) were interviewed a few days after arrival in hospital to determine reasons for patient delay and the various components of total delay time from onset of symptoms to arrival in CCU. Of the three major components of delay, decision time (time from onset of symptoms to decision to go to hospital), and hospital procedure time (time from arrival in hospital to arrival in the CCU), were of the same magnitude, 1 h 15 min and 1 h 30 min (median), whereas the median time for preparation and transportation to hospital was somewhat shorter, being 45 min. Decision time appeared to be similar in patients with confirmed and non-confirmed acute myocardial infarction (AMI) and was not associated with intensity of pain or infarct size. Half of the patients hesitated to go to hospital, which resulted in a prolonged decision delay (3 h). It is concluded that patient indecision to seek medical help is the most important reason for delay in hospital arrival in patients with suspected AMI. PMID- 2254725 TI - Bartter's syndrome and diabetes mellitus. AB - We here report a case of Bartter's syndrome occurring in association with diabetes mellitus. The patient, an insulin-dependent diabetic, presented with hypokalaemia, inappropriate kaliuresis and metabolic alkalosis. He had high plasma renin activity, relatively low plasma aldosterone, and resistance to infused angiotensin II. A high potassium diet raised total body potassium and serum potassium, did not affect plasma renin activity, but raised plasma aldosterone significantly and did not alter the resistance to angiotensin II. Indomethacin administered acutely reduced urinary potassium and kallikrein excretion and, on chronic administration, lowered plasma renin activity, urinary chloride excretion, and raised serum potassium. Salt restriction resulted in a prompt and significant reduction in urinary sodium and chloride excretion. Urinary kallikrein excretion was very high throughout, increased with sodium restriction, and decreased with sodium loading. Oral potassium supplementation partially corrected the hypokalaemia, but did not affect blood sugar control. In this patient the primary defect appears to have been primary urinary potassium wasting, rather than sodium or chloride wasting. The striking effects of indomethacin suggest that prostaglandins may play a fundamental role in the genesis of the syndrome. PMID- 2254726 TI - Renal artery stenosis and ACE inhibitor. PMID- 2254727 TI - Chronic infectious mononucleosis. PMID- 2254728 TI - Detection of occult bone metastasis by MRI scan. AB - Back pain is a common complaint in patients with cancer. The standard diagnostic approach includes plain roentgenograms and radionuclide scans. We report two patients who presented with back pain and had unremarkable or equivocal roentgenograms and radionuclide scans. Their MRI scans demonstrated metastatic disease to the bone and spinal cord compression. The role is discussed of MRI scanning in patients with solid tumors and persistent back pain. PMID- 2254729 TI - Hyperthyroidism and periodic paralysis. AB - The periodic paralyses are a rare group of disorders which may be familial, sporadic, occur in association with hyperthyroidism or as a result of potassium loss. A 46-year-old otherwise healthy Filipino male is described who presented with a second episode of paroxysmal painless weakness. Examination revealed a pattern of weakness consistent with a myopathic process (symmetric/proximal). The neurologic examination was otherwise physiologic. The clinical features are described as well as the differential diagnosis, pathophysiology, and treatment. This case also demonstrates the phenomenon wherein periodic paralysis may precede clinical hyperthyroidism. PMID- 2254730 TI - Oral contraceptives and risk of breast cancer. AB - Use of oral contraceptives (OCs) by women before age 25 or first full-term pregnancy has been theorized to increase the risk of breast cancer. While multiple studies have reported a positive relationship between early use and subsequent breast cancer development, numerous researchers have concluded there is no effect. One reason for the varied results may be the case control methodology utilized by the majority of studies and its associated biases including selection, information, and recall bias. Other theories include an undetected latent effect, changing dosages and formulations, earlier breast cancer diagnosis and follow-up among OC users, and chance. While more research is needed, the weight of evidence supports no increased risk of breast cancer among OC users, including women less than 25 years of age and before first full-term pregnancy. Hence, it seems unnecessary to change the current approach toward OC use. PMID- 2254731 TI - Hospital costs for cocaine-exposed infants. AB - A retrospective study was done at University Medical Center at Jacksonville for the period November 1988 through October 1989 to estimate the cost of treatment for 207 infants from cocaine-exposed pregnancies, 151 (76%) black and 56 (24%) white. The mean age of the mothers was 26. Twenty-five (12%) infants were admitted into the neonatal intensive care nursery (NICU) and 82 (88%) into the normal nursery where 45% of total days was due to "social hold" pending clearance for discharge by the Florida Department of Health and Rehabilitative Services. Average stay was 21.5 days in the NICU and 6.7 days in the normal nursery. Average costs varied from $36,481 for NICU to $801 for normal nursery in excess of the usual charge for a normal full-term infant. Laboratory fees accounted for the largest percentage (41.5%) of the total cost of hospitalization in the NICU, while rooming charges are the major factor (50.8%) in the normal nursery. Total charges in the 12-month period amounted to $1,057,921 or $5,110 per patient and for a control group $520,251 or $2,513 per patient. A major concern above the cost of treatment is the special education needs when these children enter the school system. PMID- 2254732 TI - Do-not-resuscitate orders. AB - Do-Not-Resuscitate (DNR) orders were audited in October and December 1989 at the teaching hospital of the University of Florida College of Medicine in Gainesville. October audit results were presented at a medical staff meeting in November to determine if education would improve compliance. There were 22 DNR orders in October, 17 (77%) were out of compliance with hospital policy due to failure to obtain written consultation from a second attending. Although not required by hospital policy, there were 11 instances (50%) in which patients (or families) were required to provide written documentation of their wishes (a living will) before the attending would write the order. There were 22 DNR orders in December, eight (36%) were out of compliance due to failure to obtain written consultation from a second attending. There were no instances of attendings' requiring patients (or families) to provide written documentation of their wishes. Education improved compliance with hospital DNR policy, but physicians were still reluctant to obtain consultation from colleagues. PMID- 2254733 TI - Medicare at 25. A busted dream. PMID- 2254734 TI - Medical McCarthyism. National Practitioner Data Bank. PMID- 2254736 TI - Mental health in the 90s. PMID- 2254735 TI - Chiropractic caveats. PMID- 2254737 TI - Dual perspective. Family member and mental health professional. PMID- 2254738 TI - A consumer's report. Psychiatric survival. Case record of Angela Fazio. PMID- 2254739 TI - Homeless mentally ill in the nineties. PMID- 2254740 TI - Adolescent suicide. Risk factors and prevention. PMID- 2254741 TI - Changes in psychotherapy. PMID- 2254742 TI - Childhood psychiatric disorders. Focus on conduct disorders. AB - The high prevalence of child and adolescent psychiatric disorders in general and of aggressive behaviors in particular presents a serious problem. Recent social, economic and demographic trends suggest that the problem is likely to grow in degree of seriousness. It is recommended that the broad social and economic policies that impact on risk factors be evaluated and that greater emphasis be placed upon prevention efforts. These efforts need to particularly strengthen the social, emotional, and economic supports that provide an important protective factor for children and families. Practices in education, employment, health, and human services need to be examined to insure that they provide support. Perhaps the most encouraging development is the growth of children's services councils. There needs to be support for their continuing growth and for the development of more effective partnerships between state and local government. A particular focus should be upon strengthening neighborhoods and local communities, involving schools and school-based services as a source of support for families, and the increasing involvement of local civic and religious groups. PMID- 2254743 TI - Obstacles confronting consumer advocates. An overview of health-related issues. PMID- 2254744 TI - How presuit screening can help the uninsured Florida physician. PMID- 2254746 TI - Physicians must not be mercy killers. PMID- 2254745 TI - Hope out of chaos. PMID- 2254747 TI - Structure, function and evolution of picornaviruses. PMID- 2254748 TI - Infectious cucumber mosaic virus RNA transcribed in vitro from clones obtained from cDNA amplified using the polymerase chain reaction. AB - Full-length cDNA to RNA 1, RNA 2 and RNA 3 of cucumber mosaic virus strain Q (CMV Q) was amplified using the polymerase chain reaction (PCR). The first-strand primer contained a BamHI site and sequences complementary to the 3' terminus of the RNA. The second-strand primers contained a BamHI site, a T7 promoter and sequences corresponding to the 5' terminus of each RNA. After cleavage with BamHI, the PCR products were cloned into the BamHI site of the vector pEMBL9(+). Five clones of each RNA were selected and RNA transcripts were synthesized in vitro from each clone using T7 RNA polymerase. The constructs were designed to allow transcription to initiate precisely at the 5' terminus of each RNA. All the transcripts were found to be infectious when inoculated onto Nicotiana tabacum cv. Samsun plants in sets of three, corresponding to RNA 1, RNA 2 and RNA 3. Of the transcript sets, four induced symptoms indistinguishable from symptoms induced by CMV-Q RNAs. However a fifth transcript set induced much more severe symptoms. Plasmids were also constructed to allow synthesis of transcripts with one or two additional G residues at the 5' terminus of each RNA. Although the yields of such transcripts synthesized in vitro with T7 RNA polymerase were higher, their infectivity was lower than that of those with no additional residues at their 5' termini. PMID- 2254749 TI - Expression of plant virus genes in animal cells: high-level synthesis of cowpea mosaic virus B-RNA-encoded proteins with baculovirus expression vectors. AB - The baculovirus expression system has been used to produce non-structural proteins encoded by bottom-component RNA (B-RNA) of cowpea mosaic virus (CPMV). For this, cDNAs containing the 60K, 87K, 110K and 170K protein coding sequences were each provided with an ATG start codon and the cDNA containing the 60K coding sequence with a TAA stop codon immediately downstream of the coding sequence. Recombinant baculoviruses were retrieved which harboured the modified B-cDNA sequences under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Upon infection of Spodoptera frugiperda cells with these recombinant baculoviruses, proteins were produced which were indistinguishable from the viral proteins found in CPMV-infected plants as judged by their migration in polyacrylamide gels and their reactivity with CPMV-specific antisera. Specific processing of CPMV polyproteins in cells infected with the 110K- and 170K-encoding baculovirus recombinants proved that the CPMV-encoded 24K protease activity contained in these polyproteins is active in these cells. Approximately 10% of the 110K protein was processed into 87K and 24K proteins and the 170K protein almost completely into the 110K, 87K, 84K, 60K and 24K polypeptides. In S. frugiperda cells infected by recombinant AcNPVs harbouring the 87K or 110K coding sequences, the CPMV-specific proteins amounted to 10 to 20% of the total cellular protein content, whereas in cells infected by recombinants encoding the 60K and 170K polypeptides the amounts of CPMV-specific proteins synthesized were much lower. Northern blot analysis indicated that the low-level synthesis of the 60K and 170K polypeptides was not due to inferior transcription of the cloned genes but was probably the result of inefficient translation of the RNAs derived from these constructs. It is concluded that plant virus genes can be efficiently expressed in an animal cell expression system to yield proteins that are structurally and, in at least one case (24K protein), functionally identical to the authentic plant virus proteins. PMID- 2254750 TI - Detection and typing of maize streak virus and other distantly related geminiviruses of grasses by polymerase chain reaction amplification of a conserved viral sequence. AB - The application of the polymerase chain reaction DNA amplification technique to the detection and typing of isolates of maize streak virus (MSV) and other related geminiviruses of grasses is described. The oligonucleotide primers used for amplification were 17-mers which contained a number of degeneracies. An approximately 250 base pair fragment was amplified from all geminivirus-infected grass and cereal samples tested. The amplification reaction was specific, working down to a concentration of 50 fg/ml of MSV-specific plasmid-cloned DNA and with a 10(-9) dilution of MSV-infected maize DNA extract. DNA could also be amplified from distantly related geminiviruses, including two different sugarcane viruses, digitaria streak virus and another as yet uncharacterized virus of a Panicum sp. Amplified DNA from a Mauritian sugarcane isolate (SSV-M) was cloned and sequenced. Sequence comparison and phylogenetic analysis showed that this sequence differed sufficiently from the analogous region of other geminiviruses for SSV-M to be considered a distinct virus. The use of the polymerase chain reaction for the amplification of gemini- and other virus genomes or genomic fragments for typing, mapping, phylogenetic analysis and taxonomy is discussed. PMID- 2254751 TI - The molecular cloning and nucleotide sequencing of the 3'-terminal region of Ornithogalum mosaic virus. AB - DNA complementary to the 3'-terminal 3684 nucleotides of the Ornithogalum mosaic potyvirus (OMV) genome was cloned and sequenced. The sequence consisted of a single large open reading frame which probably starts upstream of the cloned region. By comparison to other sequenced potyviruses, it was estimated that the clone contained the 3' non-coding (3'-NC) region, the coat protein (CP) gene and the large nuclear inclusion protein (NIb) gene, as well as approximately 85% of the small nuclear inclusion protein (NIa) gene. The 3'-NC region of 274 nucleotides showed 38% to 45% similarity to the corresponding regions of other potyviruses. The putative CP gene could encode a 253 amino acid coat protein with a calculated Mr of 28,807. Analysis of the amino acid sequences of OMV and other potyvirus proteins showed similarities of 66% to 77% for CP, 72% to 73% for NIb and 63% to 71% for NIa proteins. These data, as well as phylogenetic analysis of the CP sequences, suggested that OMV is a typical but taxonomically distinct potyvirus. PMID- 2254752 TI - Monoclonal antibodies to rabbit haemorrhagic disease virus and their use in the diagnosis of infection. AB - Hybridomas producing monoclonal antibodies (MAbs) to rabbit haemorrhagic disease virus (RHDV) were prepared. Using Western blot (WB) analysis, the MAbs obtained were divided into two groups, one reacting with the major structural proteins of Mr 61K and 38K, and the other giving negative reactions. Both groups of MAbs, however, reacted specifically with RHDV in ELISA and by immunoperoxidase (IP) and immunofluorescence (IF) tests with infected cells. As demonstrated by WB using RHDV-specific MAbs and a MAb to feline calicivirus (FCV) strain F9, the major structural (capsid) proteins of RHDV and FCV have very similar sizes (Mr61K and 38K compared to 62K to 64K and 40K respectively). No cross-reactions of MAbs with proteins of the other virus were observed in WB analysis, ELISA, IP tests or IF. The high specificity and sensitivity of RHDV-specific MAbs make them suitable for the routine IP and IF diagnosis of RHDV in liver cells of rabbits dying after natural or experimental infections. PMID- 2254753 TI - Characteristically distinct isolates of the nuclear polyhedrosis virus from Spodoptera litura. AB - More than 100 isolates were plaque-purified to examine the genetic variations in four wild stocks of Spodoptera litura nuclear polyhedrosis virus (NPV) collected in Japan. These isolates were characterized by their in vitro host range in three established insect cell lines, growth characteristics, polyhedral protein, DNA restriction endonuclease pattern and DNA hybridization. The isolates were separated into four distinct groups: (I) isolates corresponding to Autographa californica NPV, (II and IV) two different groups of isolates of S. littoralis NPV which had been previously characterized and (III) isolates with no correspondence to any reported virus group. Of the S. litura NPV wild stocks, two were mixtures of more than two different groups of NPVs. We have discussed the advantage of having a mixture of different NPV groups in the same wild virus stocks. PMID- 2254754 TI - Purification and characterization of the infectious hypodermal and haematopoietic necrosis virus of penaeid shrimps. AB - Infectious hypodermal and haematopoietic necrosis (IHHN) is one of the most important viral diseases of cultured penaeid shrimps and is potentially a limiting factor in the development of farming projects for some species of these shrimps. Although the IHHN agent was recognized early as being viral in origin, attempts to characterize it were inconclusive because of difficulties in obtaining sufficient amounts of purified virions to permit its characterization. Recent improvements of purification procedures have allowed the physicochemical characterization of this virus. Purified IHHNV is a non-enveloped icosahedral particle averaging 22 nm in diameter, exhibiting a mean buoyant density of 1.40 g/ml in CsCl. The genome is a single molecule of ssDNA with an estimated size of 4.1 kb by molecule length measurement in transmission electron microscopy. As determined by SDS-PAGE, the particle contains four polypeptides with Mrs of 74K, 47K, 39K and 37.5K, respectively. From its characteristics, this virus could be a member of the Parvoviridae family. PMID- 2254755 TI - Physicochemical analysis of the hepatitis B virus core antigen produced by a baculovirus expression vector. AB - The hepatitis B virus particle consists of an envelope carrying the surface antigen of the virus and an internal capsid consisting of the core antigen (HBcAg). The internal capsid contains the circular, partially dsDNA genome and the viral polymerase. Empty core particles have been produced in Spodoptera frugiperda cells using a recombinant baculovirus vector, YM1KTc, that expresses a 21.4K derivative of the HBcAg gene. The particles have been purified to homogeneity by caesium chloride density gradient centrifugation followed by glycerol gradient centrifugation. Physicochemical analysis of the core particles showed that they exhibited a sedimentation coefficient (s20,(0)w) of 82.5S and a diffusion coefficient (D) of 1.28 x 10(-7) cm2/s. The Mr obtained by substitution of these values in the Svedberg equation was 5.8 x 10(6), using a partial specific volume of 0.73 ml/g for the viral protein as estimated from the amino acid composition. The Mr determined from sedimentation equilibrium analyses was 6.3 x 10(6). Spectrophotometric and metabolic labelling analyses failed to detect nucleic acids in the core preparations. The data are at variance with the prediction that cores exhibit a T = 3 symmetry and contain some 180 subunits. The results suggest that the baculovirus-expressed cores may contain up to 300 subunits of HBcAg protein. PMID- 2254756 TI - Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route. AB - A murine model based on infection by the respiratory route has been used to study the pathogenesis of recombinant vaccinia viruses. The neurovirulent Western Reserve (WR) strain and the Wyeth smallpox vaccine strain were used as vectors. Recombinant viruses were constructed by insertion of the Epstein-Barr virus membrane glycoprotein 340 gene into the thymidine kinase (TK) gene of each vaccinia virus. Intranasal inoculation of DBA/2 mice with 10(6) pock-forming units (pk.f.u.) of the WR strain was lethal but mice survived similar infection with the WR recombinant virus. Each virus was recovered from lung, blood and brain but, unlike wild-type virus, the recombinant virus was subsequently cleared. No deaths occurred after similar infection with the Wyeth strain or the Wyeth recombinant virus. There was limited growth of the Wyeth strain in the respiratory tract, low levels of virus in the blood and only sporadic recovery in brain extracts. The Wyeth recombinant virus was cleared rapidly with little viraemia or detectable infection of the central nervous system. No phenotypic character determined in vitro could be related consistently to the virulence of wild-type and recombinant viruses. Although the lethal character of the WR strain was affected by its TK+ phenotype, mice survived infection by intranasal inoculation with 10(6) pk.f.u. of WR TK+ recombinant viruses which either expressed the human interleukin 2 gene or had a deficient vaccinia virus growth factor gene. PMID- 2254757 TI - Sequence of the 3'-terminal region of turnip mosaic virus RNA and the capsid protein gene. AB - A sequence of 1801 nucleotides originating from the 3' end region of turnip mosaic virus (TuMV) RNA was cloned using the polymerase chain reaction and found to contain one long open reading frame (ORF). The amino acid sequence of three different regions of the isolated TuMV capsid protein (including the NH2 terminus) was determined and these partial sequences were found in the translation product predicted to be encoded by the large ORF. The data suggested that the TuMV capsid protein was a product arising from the maturation of a larger polyprotein, as observed for other potyviruses. Furthermore, the putative cleavage site corresponded to a glutamine-alanine dipeptide, a site commonly used in plant virus polyprotein processing. The capsid protein cistron was composed of 864 nucleotides and corresponded to a region encoding 288 amino acids with a calculated Mr of 33,186; the adjacent 3' non-coding region was 667 nucleotides long. The deduced amino acid sequence of the TuMV capsid protein is closely related to other potyvirus capsid proteins, with most of the variation being found within the NH2-terminal region. PMID- 2254758 TI - Limiting dilution analysis of lymphokine-activated killer cell precursor frequencies in peripheral blood lymphocytes of cancer patients receiving interleukin-2 therapy. AB - Eleven patients receiving weekly cycles of therapy with recombinant interleukin-2 (IL-2) were evaluated with a sensitive limiting dilution analysis to determine lymphokine-activated killer (LAK) cell precursor frequencies in peripheral blood lymphocytes. An increase in LAK precursor frequency above baseline was suggested by day 6 of this protocol and was clearly significant by day 20, indicating an expansion of the circulating precursor pool results from in vivo IL-2 administration. Correlations were not significant between LAK precursor frequency during IL-2 therapy and the total number of circulating lymphocytes, the percentage of CD56+ lymphocytes, IL-2 proliferative responses, or LAK activity of peripheral blood lymphocytes, indicating that the precursor frequency identification based on functional testing of individual cells is not accurately reflected by these analyses of heterogeneous bulk populations. Selective cell depletion analyses revealed that the majority of LAK precursors after in vivo IL 2 therapy were cells with the natural killer phenotype. Analysis of LAK precursors may help define the in vivo IL-2 administration, alone or in combination with other hematopoietic or immunodifferentiative cytokines, necessary to further augment in vivo effector cell numbers and activity for patients with cancer. PMID- 2254759 TI - Stimulation of granulopoiesis in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor: assessment of two routes of administration. AB - We administered Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor to 61 patients with malignancy, 36 of whom had normal peripheral blood counts and 25 of whom had peripheral cytopenia due to underlying bone marrow disease, to compare the efficacy of two different routes of administration to stimulate the in vivo granulopoiesis: i.e., continuous i.v. infusion and s.c. injection. Three well-tolerated dose levels were investigated. Application of granulocyte-macrophage colony-stimulating factor resulted in dose dependent increases in circulating neutrophils, eosinophils, and monocytes and an increase in bone marrow cellularity, irrespective of route of administration. In some patients, mild side effects, including bone pain, dyspnea, flu-like symptoms, and a decrease of platelet counts, were recorded, but they were less pronounced when the hormone was administered subcutaneously. PMID- 2254760 TI - Biological response to intravenously administered endotoxin in patients with advanced cancer. AB - The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL 6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated. PMID- 2254761 TI - Initial clinical trial of the macrophage activator muramyl tripeptide phosphatidylethanolamine encapsulated in liposomes in patients with advanced cancer. AB - A phase I clinical trial of the macrophage activator, muramyl tripeptide phosphatidylethanolamine has been carried out in 37 patients (47 courses) at doses of 0.01-6.0 mg/m2 intravenously twice weekly for 4 weeks. Activation of peripheral blood monocytes and drug toxicity were used as the parameters to monitor the trial. Toxicity was acute systemic responses of fever, chills, and hypertension without a clear dose response. No major organ-related toxicity was seen. A dose of 4.0 mg/m2 biweekly produced activation of blood monocytes; a dose of 6.0 mg/m2 produced inhibition. There was one complete response of 3 months duration in a patient with renal cell carcinoma with pulmonary metastases. The optimum dose for phase II studies is in the range of 1-4 mg/m2 twice weekly for 4 weeks, a dose that is well tolerated. PMID- 2254762 TI - Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. AB - A prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS KS combining antiretroviral agents are in progress. PMID- 2254763 TI - Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study. AB - To develop effective interleukin-2 (IL-2) protocols for pediatric malignancies, it is important to define IL-2 pharmacokinetics in children. In a phase I trial, we studied IL-2 pharmacokinetics in seven children, aged 6-18, five with leukemia, one with neuroblastoma, and one with rhabdomyosarcoma. IL-2 was administered as a 15-min i.v. infusion of either 1 X 10(6) CU/m2/dose or 3 X 10(6) CU/m2/dose (every Monday, Wednesday, and Friday for 3 weeks). IL-2 levels were determined using an IL-2-dependent murine T lymphocyte cell line bioassay. Peak IL-2 levels of 120-426 and 330-740 CU/ml were achieved after the lower and higher doses, respectively. Pediatric IL-2 kinetics resembled data reported for adults, fitting a two-compartment model (least-squares-regression technique), with an alpha half-life of 14.0 +/- 5.6 min (range, 6.3-23.1) and a beta half life of 51.4 +/- 10.7 min (range, 33.0-66.0). The volume of distribution approximated total extracellular fluid (mean, 0.18 L/kg). Further clinical trials are needed to identify which pediatric malignancies are sensitive to immunotherapy and to establish the optimal treatment regimens. PMID- 2254764 TI - Indexes and boundaries for "quantitative significance" in statistical decisions. AB - Boundaries for delta, representing a "quantitatively significant" or "substantively impressive" distinction, have not been established, analogous to the boundary of alpha, usually set at 0.05, for the stochastic or probabilistic component of "statistical significance". To determine what boundaries are being used for the "quantitative" decisions, we reviewed pertinent articles in three general medical journals. For each contrast of two means, contrast of two rates, or correlation coefficient, we noted the investigators' decisions about stochastic significance, stated in P values or confidence intervals, and about quantitative significance, indicated by interpretive comments. The boundaries between impressive and unimpressive distinctions were best formed by a ratio of greater than or equal to 1.2 for the smaller to the larger mean in 546 comparisons, by a standardized increment of greater than or equal to 0.28 and odds ratio of greater than or equal to 2.2 in 392 comparisons of two rates; and by an r value of greater than or equal to 0.32 in 154 correlation coefficients. Additional boundaries were also identified for "substantially" and "highly" significant quantitative distinctions. Although the proposed boundaries should be kept flexible, indexes and boundaries for decisions about "quantitative significance" are particularly useful when a value of delta must be chosen for calculating sample size before the research is done, and when the "statistical significance" of completed research is appraised for its quantitative as well as stochastic components. PMID- 2254765 TI - Reliability of death certificate diagnoses. AB - Consistency between death certificates and clinical records from 5 general hospitals in Kuwait was studied for 470 deaths with the following underlying or associated causes: hypertensive (HYP), ischaemic heart diseases (IHD), cerebrovascular diseases (CVD) and diabetes mellitus (DM). Direct causes were not considered since they are of little interest analytically. Only deaths with definite or most probable ascertainment were included. One cardiologist, who was provided with the WHO criteria and relevant documents on death certification, independently reviewed the records. To test the reviewer's bias and the reliability of his judgement, an adjudication process was effected by having one senior cardiologist re-review a random subsample of 140 records. The two reviewers showed good agreement. Specific diagnoses criteria for deciding the underlying cause of death in multiple morbid conditions by the reviewer were followed. Due to possible reviewer bias, we aimed at measuring the difference between initial certifiers and the reviewer rather than measuring the diagnostic accuracy of initial certifiers in reference to the reviewer. The agreement index kappa showed poor agreement between original and revised certificates. The original certificates under-estimated CVD as an underlying cause of death by 69.2%, DM by 60%, IHD by 33.5% and HYP by 31.8% in our sample. Associated causes were also consistently under-estimated by initial certifiers as compared with the reviewer. This bias calls for basing mortality statistics in Kuwait on hospital death committees' reports rather than on initial certifier death certificates, use of multiple-causes of death instead of one underlying cause and adequate training of the medical profession on the value and process of death certification. PMID- 2254766 TI - Serum uric acid correlates in elderly men and women with special reference to body composition and dietary intake (Dutch Nutrition Surveillance System). AB - In 460 apparently healthy Dutch elderly, aged 65-79 years, serum uric acid correlates were studied by linear regression analyses, for men and women separately. Diuretic therapy, total serum cholesterol (women only) and creatinine clearance (in bivariate analysis only) were significantly associated with serum uric acid level. Positive associations of serum uric acid with body weight, body mass index, body fatness (men) and lean body mass (men) were observed, with and without adjustment for diuretic therapy, creatinine clearance and age. Serum uric acid levels, whether adjusted or not for these variables and for body mass index, were positively associated with alcohol intake (men) and consumption of meat and fish (women), and inversely with consumption of bread, margarine and milk products (women). These results indicate that limited medication with diuretics, weight control and restriction of alcohol use may help to prevent hyperuricemia in the elderly. PMID- 2254767 TI - Infant feeding patterns during the first year of life in Denmark: factors associated with the discontinuation of breast-feeding. AB - We prospectively studied 500 infants born consecutively in a university affiliated community hospital in Copenhagen, Denmark, over the first 12 months of life using a detailed monthly mailed questionnaire (overall response rate = 73%) which focused on feeding practices and illnesses. Seventy-seven percent of respondents breast-fed their infants at 1 month of life compared to 19% at 12 months of life. Analysis of breast-feeding behavior using survival analysis showed that 50% of the mothers who breast-fed since the first month of their infant's life were still breast-feeding at 7 months of life. Also, there was a greater than two-fold increase in the rate of discontinuation of breast-feeding for infants in daycare compared to infants not attending daycare (RR = 2.08, 95% CI = 1.43, 3.01). Discontinuation of breast-feeding was not significantly associated with the number of children in the family or with social class. These results give insight into infant feeding patterns in a developed country and suggest that: (1) breast-feeding is the dominant method of feeding during the infant's first year of life, and (2) the rate of discontinuation of breast feeding is increased by the entry of these infants into daycare. PMID- 2254768 TI - Parents' vs physicians' utilities (values) for clinical outcomes in potentially bacteremic children. AB - Our previous analyses of decision strategies in children 3-24 months with acute onset fever greater than or equal to 39 degrees C and no evident bacterial focus of infection indicated that the risks of routine blood cultures (the unnecessary hospitalization and treatment of children who clear their bacteremia spontaneously) outweigh its benefits (the prevention of a few cases with major infectious sequelae). Because those analyses were based on parents' values for beneficial and adverse clinical outcomes, we wished to examine whether those values differed in physicians and, if so, whether the differences were sufficient to change the results of the decision analysis. Using a pre-tested linear analog utility (value) scale, we evaluated eight potential clinical outcomes in potentially bacteremic children by surveying 121 parents of healthy 3-24-month old children attending a private pediatric group practice and 57 attending physicians of a tertiary-care children's hospital emergency room. Utilities were based on a 0-1 normalization, where 0 is the utility of the worst outcome (meningitis or other major bacterial infection, plus venipuncture), and 1 the utility of the best outcome (complete recovery without venipuncture or hospitalization), and were analyzed using a recently developed statistical model of utility. The majority of parents and physicians combined the imputed components of the outcomes (disease, pain of venipuncture, and stress of hospitalization) in a nonlinear fashion. Parents assigned substantially lower utility (i.e. greater disutility) to venipuncture, minor infection, and hospitalization than did physicians, and these utilities were even lower in parents with other children at home.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254769 TI - Validation of a self-administered diet history questionnaire using multiple diet records. AB - The validity of a self-administered diet history questionnaire has been estimated using as the reference data the mean of three 4-day diet records collected over the year prior to the administration of the questionnaire, in 1985-1986. Subjects were women ages 45-70 years, participants in the Women's Health Trial Feasibility Study, a multi-center clinical trial in which some women were randomized to be taught to adopt and maintain a low-fat diet, while others maintained their usual diet. The questionnaire produced group mean nutrient estimates closely approximating the values obtained by three 4-day records, e.g. in the usual-diet group, 37.7% of calories from fat by both food records and by questionnaire, and in the low-fat group, 21.3% of calories from fat by food records and 23.7% of calories from fat by questionnaire. Correlations between questionnaire and diet records for per cent of calories from fat were 0.67 and 0.65 respectively in the two groups; most correlations were in the 0.5-0.6 range, and were similar to those achievable by a single 4-day food record. PMID- 2254770 TI - Differential recall as a source of bias in epidemiologic research. AB - Differential recall between compared groups is discussed most often in the context of case-control studies. Cases, compared to controls, are suspected of providing a more complete report of their true exposure to an hypothesized risk factor, thereby biasing upwards the estimate of its effect. The present paper describes how differential recall can arise with any observational design in epidemiology; with any class of study variable, not only exposures; and may inflate or deflate the true value of the estimate of effect size. We list a variety of study designs and questionnaire tactics that aim to remedy these problems. The scope and magnitude of the bias created by differential recall and the efficacy of proposed remedies require further study. PMID- 2254771 TI - Prevalence of Raynaud phenomenon in the adult population of South Carolina. AB - A prevalence estimate for Raynaud phenomenon among adult residents of South Carolina was based on data obtained from respondents in a statewide health survey, followed by face-to-face interviews and clinical screening for Raynaud phenomenon, using a screening procedure developed by the authors. The survey obtained 5246 personal interviews from a probability sample of over 3000 households, and 494 survey subjects participated in the clinical screening. The prevalence estimates and their standard errors were computed using survey case weights, design-based estimation, and logistic modelling techniques. The prevalence of Raynaud phenomenon among adult residents of South Carolina was determined to be 3.5%, with a standard error of 0.6%. Prevalence was higher for females (4.3%, SE = 0.7%) than for males (2.7%, SE = 0.6%). These figures are much lower than most estimates in the existing literature on Raynaud phenomenon. PMID- 2254772 TI - Competing risk analysis of life table data: application to lifetime risk computation. AB - In this pedagogic note we propose to assess the safety of treatment in a clinical trial, or the effect of risk exposure in a chronic animal study, in terms of two lifetime risks. These risks are computable from life table type data and take into account the effects of competing risks. We first describe their computational procedures in detail to demonstrate the need for their implementation in a computer program. We then illustrate their practical application through use of the data obtained from an actual clinical study. PMID- 2254773 TI - Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test. AB - Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test. Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera. Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested. In each pair the "case" was a person who had recovered from severe cholera at least 6 months before testing and the "control" was a person who resided in the home of a cholera patient but remained uninfected. The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs. The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies. PMID- 2254774 TI - An inconsistent relationship between insulin and blood pressure in three Pacific island populations. AB - The evidence linking insulin to blood pressure is controversial, and results for groups similarly categorized by body mass, glucose tolerance and hypertensive status are often contradictory. We have investigated the relationship in three population-based samples of Micronesian (Nauru), Polynesian (Western Samoa) and Melanesian (New Caledonia) Pacific islanders, who are known to be susceptible to obesity, non-insulin-dependent diabetes mellitus (NIDDM), hyperinsulinaemia and hypertension. After controlling for age and body mass index (BMI), mean fasting and 2-hr (post 75 g glucose) insulin levels were not significantly different between hypertensive and non-hypertensive subjects, in any population or glucose tolerance sub-group, excepting 2-hr insulin in New Caledonians with normal glucose tolerance. Similarly, there were no strong trends for a higher prevalence of hypertension amongst those with insulin levels in the upper quartile of the distribution of each population, although it was apparent in some BMI/glucose tolerance sub-groups of two populations. Multiple linear regression analyses also showed an inconsistent and where present, weak, independent association between insulin and blood pressure in models predicting both systolic and diastolic blood pressure. We therefore conclude that the hypothesis implicating insulin as a major determinant of blood pressure and as the pathophysiological link between obesity, NIDDM and hypertension is not strongly supported either by the literature or the present data. PMID- 2254775 TI - Tampon absorbency, composition and oxygen content and risk of toxic shock syndrome. AB - Tampon use has been identified as a major risk factor for toxic shock syndrome, although the etiologic role of tampons is not clearly understood. Two epidemiologic studies conducted to date have reported an association between tampon absorbency and risk of toxic shock syndrome. This finding is not corroborated by laboratory studies, however, which have suggested that absorbency may be a marker for other characteristics that create an environment conductive to the elaboration of toxic shock syndrome toxin 1. We used data from the previously reported Tri-state study to estimate simultaneously the effects of tampon oxygen content, absorbency and chemical composition. Although the data are sparse, oxygen content was more strongly associated with risk of toxic shock syndrome than either absorbency or chemical composition. The results suggest that it may be possible to develop a highly absorbent tampon that is not associated with a high risk of toxic shock syndrome. PMID- 2254776 TI - A method of pharmacoepidemiologic analysis that uses computerized Medicaid. AB - A method of pharmacoepidemiologic data analysis that utilizes computerized Medicaid data is presented. A cohort design in which Medicaid enrollees receiving drugs that are normally used to treat similar underlying conditions is described. A period of time in which Medicaid service transactions are evident is required before an individual is eligible for selection into a cohort. Selection of study subjects and descriptions of cohorts are based on Medicaid service histories occurring during the preliminary, prerequisite period. Time at risk is considered to begin after a prescription for a study drug is dispensed and continues until either a refill is dispensed, a prescription for an alternative drug within the same therapeutic class is dispensed, or a predetermined number of days has passed. Subjects are followed forward in time and relevant health care transactions that are suggestive of suspected adverse drug reactions are noted. Incidence densities associated with sequentially ranked prescriptions within sequential courses of therapy are compared. Methods to increase the accuracy of case ascertainment are briefly discussed. Separate validation studies may be used to evaluate the validity of computerized case ascertainment methods and to compensate for misclassification of outcome. The proposed method is intended to provide timely estimates of risk for selected outcomes. For outcomes that cannot be accurately ascertained from computerized data, this method may be useful in determining the feasibility of more customized studies. PMID- 2254777 TI - Interobserver variation in histopathological grading of cervical dysplasia. AB - In order to assess the variability among histopathologists in grading cervical dysplasia, four experienced histopathologists examined the same set of 106 biopsy specimens and assigned them to one of five diagnostic categories. These were: no dysplasia, mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ. The histopathologists did not discuss the grading criteria beforehand. There was considerable disagreement among the pathologists: unweighted group kappa 0.28, weighted group kappa 0.56. It appeared that all grades of dysplasia were equally difficult to distinguish from adjacent categories. Various explanations for this interobserver variation are put forward. PMID- 2254778 TI - Predictors of quitting smoking: the NHANES I followup experience. AB - There are no published prospective studies on the predictors of spontaneously quitting cigarette smoking in a nationally-representative U.S. population. This paper describes such a study, using a cohort taken from the First National Health and Nutrition Examination Survey (NHANES I, 1971-1975) and traced by the NHANES I Epidemiologic Followup Survey (1982-1984). "Successful" quitting (for at least 1 year at time of followup) was ascertained among 4779 adults (age 25-74 years) who were smokers at the time of NHANES I and not disabled at followup. Independent predictors of quitting (by proportional hazards multiple regression) were: (1) older age; (2) White race; (3) fewer cigarettes smoked/day; (4) higher household income; and (5) hospitalization in the followup period. Predictors of relapse (ex smokers at NHANES I who were smoking again at time of followup) were: (1) younger age; (2) urban residence; and (3) female gender. These findings have implications for intervention strategies, public health projections and further research. PMID- 2254779 TI - Alcohol consumption and blood pressure: a comparison of native Japanese to American men. AB - We compared the cross-sectional association of alcohol consumption with blood pressure in 810 Japanese men (JM) living in Tokyo and 946 white men (WM) living in New York. Mean systolic (JM and WM, p less than 0.001) and diastolic blood pressure (JM, p less than 0.002; WM, p less than 0.001) were associated with alcohol consumption in both groups. Compared to abstainers, the heaviest drinkers had the highest systolic (JM, p = 0.001; WM, p less than 0.01) and diastolic (JM, p less than 0.002; WM, p less than 0.05) blood pressures. The relation of blood pressure to alcohol intake was J-shaped in the Americans, but linear in the Japanese. Exploratory analyses revealed that the J-shape may have been due to under-reporting of heavy alcohol ingestion by American abstainers. When abstainers were excluded, the relationships were similar in both the American and Japanese. The positive association between blood pressure and alcohol consumption persisted after adjustment for age, cigarette smoking, use of antihypertensive medications, body mass index, heart rate, abdominal skinfold thickness, hematocrit, fasting blood glucose, serum uric acid levels and urinary sodium/potassium ratio. Alcohol use was also related to prevalence of hypertension. These findings confirm the presence of an independent association between alcohol intake and blood pressure in both JM and WM and suggest that, despite differences in the metabolism of alcohol, the relation of alcohol consumption to blood pressure is similar in both nationalities. PMID- 2254780 TI - Examination by logistic regression modelling of the variables which increase the relative risk of elderly women falling compared to elderly men. AB - In a community based, prospective study to determine risk factors for falls, 465 women and 296 men 70 years and over were followed for 1 year and 507 falls were documented. A greater proportion of women (32.7%) than men (23.0%) experienced at least one fall in which there was no or minimal external contribution. Using unconditional logistic regression models we investigated the effect of physical and sociological variables on the sex difference in fall rate. Controlling for the variables age, use of psychotropic drugs, inability to rise from a chair without using arms, going outdoors less than daily and living alone decreased the relative risk of women falling compared to men from 2.02 (95% CI, 1.40-2.92) to 1.55 (95% CI 1.04-2.31). Some of the increased risk of falling associated with being a women was able to be explained and is potentially correctable. But even after controlling for the physical and social variables which we had assessed, women compared to men still had a significantly increased relative risk of falling. PMID- 2254782 TI - Recall bias in epidemiologic studies. PMID- 2254781 TI - Patterns of non-response to a mail survey. AB - This paper describes a basic investigation of possible non-response bias in a mail survey. We compare characteristics of responders and non-responders to a mail survey of health outcomes among participants of a longitudinal study of physical activity, physical fitness, and health. Results indicate that, at the first clinic visit, the responders were essentially the same as the non responders on personal health history and laboratory measurements, while reporting significantly more family history of specific chronic diseases (cardiovascular disease, hypertension, stroke). The male responders were younger and reported more positive health behaviors as well as better weight and treadmill times at the first clinic visit. These results suggest that both response groups were equally healthy at entry, and that individuals who had family members with certain chronic conditions and who had positive health behaviors were more likely to respond (participate) in this health-related survey. Differences of this type could affect interpretation of future analyses. This work illustrates the importance of incorporating methods to examine non response into any epidemiologic study. PMID- 2254783 TI - Can vasectomy reduce the sexual transmission of HIV? PMID- 2254784 TI - The SUPPORT study. Introduction. PMID- 2254785 TI - SUPPORT: Study to understand prognoses and preferences for outcomes and risks of treatments. Study design. PMID- 2254786 TI - Background for SUPPORT. PMID- 2254787 TI - Phase II: influencing decision making in SUPPORT. PMID- 2254788 TI - Patient characteristics in SUPPORT: sociodemographics, admission diagnosis, co morbidities and acute physiology score. PMID- 2254789 TI - Patient characteristics in SUPPORT: activity status and cognitive function. PMID- 2254790 TI - Patient characteristics in SUPPORT: functional status. PMID- 2254791 TI - Decision making in SUPPORT: introduction. PMID- 2254792 TI - Data collection strategies in SUPPORT. PMID- 2254793 TI - Decision making in SUPPORT: patient perceptions and preferences. PMID- 2254794 TI - Decision making in SUPPORT: the role of the nurse. PMID- 2254795 TI - Decision making in SUPPORT: physician perceptions and preferences. PMID- 2254796 TI - Decision making in SUPPORT: physician characteristics. PMID- 2254797 TI - Decision making in SUPPORT: sentinel decisions. PMID- 2254798 TI - Assessing quality of life and preferences in the seriously ill using utility theory. PMID- 2254799 TI - Collaborating hospital characteristics and their health-care and legal environments in SUPPORT. PMID- 2254800 TI - Outcomes in SUPPORT. PMID- 2254801 TI - Statistical methods in SUPPORT. AB - The analysis and interpretation of the data collected in SUPPORT provide great potential for understanding the relationships among treatment choices, patient and physician values and preferences, perceptions about the risks and benefits of treatments, institutional characteristics, and outcomes (as measured by quality of life, survival, and satisfaction). The complicated analyses required to elucidate these relationships will pose many technical challenges in dealing with longitudinal observational data collected from seriously ill patients at multiple sites. Major challenges include the handling of incomplete data, proper parameterization of treatment effects, strategies to avoid various potential biases, validating predictive models, and constructing endpoints that combine survival with quality of life. Within the structure of the SUPPORT study, mechanisms have been established to guide the analyses and to ensure their quality and validity. PMID- 2254802 TI - A population-based study of the prevalence and outcome of serious illnesses in adults. PMID- 2254803 TI - Multilayer model of photon diffusion in skin. AB - A diffusion model describing the propagation of photon flux in the epidermal, dermal, and subcutaneous tissue layers of the skin is presented. Assuming that the skin is illuminated by a collimated, finite-aperture source, we develop expressions relating photon flux density within the skin and intensities re emitted from the skin surface to the optical properties of the individual layers. Model simulations show that the rate at which re-emitted intensities diminish with radial distance away from the source can provide information about absorption and scattering in underlying tissues. Re-emitted intensities measured from homogeneous and two-layer tissue phantoms compare favorably with model predictions. We demonstrate potential applications of the model by estimating the absorption (sigma a) and transport-corrected scattering (sigma's) coefficients of dermis and subcutis from intensities measured from intact skin and by predicting the magnitude of the optical-density variations measured by a photoplethysmograph. PMID- 2254804 TI - [Serial change of perilymphatic potassium ion concentration in the scala tympani after introducing KCl-solution into the guinea pigs' tympanic cavity]. AB - Characteristic nystagmus similar to the Meniere's attack could be observed after introducing KCl solution into the tympanic cavity of guinea pigs. To confirm the fact that this nystagmus was provoked by the high perilymphatic potassium ion concentration, the K+ activity of perilymph was recorded serially through the K+ specific microelectrode inserted into the scala tympani. The rapid increment of K+ activity reached maximum at 120 minutes after introducing KCl solution, and then it decreased gradually to a half of the maximum activity. However, such change of perilymphatic potassium ion concentration was not observed by introducing sucrose solution as control. PMID- 2254805 TI - [Recurrence of perilymphatic fistula]. AB - Recurrence of the perilymphatic fistula is not rare and may be a tough problem for surgical treatment. This is because a graft is usually applied on the ruptured window(s) from the middle ear and therefore the perilymphatic pressure directly acts on the graft. The recurrence may be caused by a technical failure, use of an unsuitable graft material, poor postoperative bedrest, trauma, increased inner ear pressure, etc. In our clinic, the recurrence occurred in 7 of 48 cases surgically treated. Vertigo accompanied with spontaneous or positional nystagmus was seen in all 7 recurrent cases, while only 2 of them complained of worsening of the existing hearing loss. Re-operation was carried out in two patients. In the first case, closure of the round window by the previous operation was found incomplete, and the perilymph leaked through the gap around the graft. In the second case, closure of the round window was complete, but perilymph leaked from the oval window. In order to prevent the recurrence, the operation should be carefully performed by using strong and adhesive tissue as a graft material, applying a glue between the graft and the inner ear window(s), and keeping strict postoperative bedrest. PMID- 2254806 TI - [Leukemic infiltration of the mastoid bone--cytologic examination of exudate in the tympanic cavity as a useful diagnostic method]. AB - Although otologic involvement by leukemic infiltration was supposed to be unusual, increasing number of cases have been reported in recent years, probably due to the advance of chemotherapy, improved remission rate and longer survival of leukemic patients. Two cases of myelogenous leukemia with infiltration of mastoid bone were reported. One is 15-year-old girl with acute myelogenous leukemia, which had been well controlled for 1 year, developed a sudden onset of facial nerve palsy. The other is 30-year-old female with chronic myelogenous leukemia and blastic crisis, complained hearing loss. As both cases had exudate in the tympanic cavity, the punctures were carried out through the eardrum. The pathological study of these exudate cells revealed the involvement of mastoid bone by leukemia. The cytologic examination of exudate in the tympanic cavity is simple, time-sparing and of little burden to the patient. This technique is very useful and supposed to take the place of the exploratory surgery of mastoid cavity which is previously considered necessary for the correct diagnosis. PMID- 2254807 TI - [Clinical applications of three-dimensional CT images for diseases of the anterior and middle cranial base]. AB - CT scanning has made significant contributions to the diagnostic, therapeutic and prognostic aspects for the managements of the lesions in the paranasal sinuses and the orbit. The current availability of 3-D imaging reformatted from CT scans has added a new dimension to anatomic investigations and pre- and postoperative evaluations of the skull base structures. Twenty-five craniomaxillofacial 3-D CT examinations were performed during the year of the 1989 for the purpose of the diagnosis of the pathology, surgical planning and postoperative evaluation in reconstructive surgery of the skull base. RESULTS: 1. The use of 3-D CT improves the display of the location and volume of the pathology and affords the accurate therapeutic and surgical planning. 2. Preoperative 3-D CT imagings are useful for the display of the bony erosion of the skull base. Stereotaxic 3-D CT imagings are particularly appreciated in the diagnostic aspects of the management of the pathology. 3. In the reconstructive surgery of the skull base, an accurate prefabricated model of the bony defect can be made to aid the surgery. 4. A major limitation of 3-D CT is its inability to reconstruct the pathology of soft tissues with the same fidelity afforded bony structures. PMID- 2254808 TI - [A study of the relationship between hearing-aid usage and residual hearing]. AB - Fifty-eight children (from 4 to 19 years of age) with bilateral, symmetrical, sensorineural hearing loss, who had used a hearing aid in only one ear for 1 to 19 years were investigated to study the influence of hearing-aid upon the residual hearing between the used and no used ears. The results were as follows, 1) The average hearing level for the used ear at seven frequencies was 49. 5 dB of pre-hearing-aid usage and was 53. 8 dB of post-hearing-aid usage. The discrepancy of audiograms between the aided and unaided ear was not remarkable. 2) The hearings for both the aided and the unaided ears in Audiograms was progressive for a long time. But no significance relation was observed between changes in used-ear hearing of the aided and unaided ears. 3) When the hearing levels of the children were scrutinised on an individual basis, it was found that 9 cases (15.5%) in both ears, 2 cases (3.4%) in only used ear and 1 case (1.7%) in only no used ear out of 58 cases showed deterioration of hearing. 4) These data did not lead us to the conclusion that hearing-aid usage was detrimental on the residual hearing of children with sensorineural hearing loss. PMID- 2254809 TI - [Middle ear air volume and prognosis of secretory otitis media]. AB - Ninety ears (52 patients, aged 3-11 years) affected by secretory otitis media (SOM) were treated by insertion of ventilation tubes (VT). Following insertion of the VT, middle ear air volume of these ears was estimated using an impedance audiometer, at 1, 3, and 6 months postoperatively, and every 3 months thereafter. The middle ear air volume, expressed as the compliance value, increased rapidly for the first 3 months followed by a gradual increase thereafter. A great difference among the compliance values of ears was observed, values ranging from over 10 cc to below 1.5 cc at 6 months, postoperatively. Twelve percent of the ears had compliance values of less than 1.5 cc, and in this group, CT showed opacified and poorly developed mastoid cells. Although the association of upper respiratory disorders such as chronic sinusitis, nasal allergies and cleft palates were found to be more frequent in cases of ears with smaller compliance values, this was not statistically significant. Small compliance values (middle ear air volume) were correlated with the early onset of acute or secretory otitis media, repeated otorrhea after VT insertion and high recurrence rates after the extrusion of the VT. PMID- 2254810 TI - [Mechanical impedance of the human mastoid and forehead--a critique of the mechanical coupler of the IEC373]. AB - Mechanical impedances of human mastoids and foreheads were measured on frequencies from 250 to 6300 Hz for 80 young adults by means of B&K impedance head (#8000) and shaker (#4810) as main parts of the measuring setup. The measurements revealed the following problems in the IEC373 (1971/1981) which had defined the mechanical impedance characteristics of the mechanical coupler for calibration of bone vibrators in audiometric use. The average impedance levels of the mastoids differ significantly from those of the foreheads in middle and high frequencies. The impedance levels of the IEC373 mechanical coupler are higher than those of the present measurements of the mastoids and the foreheads. The differences exceeded the tolerance limits of IEC373 (1981) in every frequency. These findings strongly suggest that the coupler is neither the artificial mastoid nor the artificial forehead but a coupler having a specified impedance, therefore, disregard for effect of the type of bone vibrator on the Reference Equivalent Threshold Force Level, as seen in ISO7566, should be revised and that the RETFL should be determined for an each type of bone vibrator. PMID- 2254811 TI - [Immunohistochemical study of the endolymphatic hydrops due to secondary endolymphatic sac immune reaction]. AB - Secondary endolymphatic sac (ES) immune response against keyhole limpet hemocyanin (KLH) were immunohistochemically investigated in guinea pigs by analysing the distribution of IgG and C3 complement in the inner ear over a 4 week period. After systemic sensitization with KLH and Freund's adjuvant, KLH was inoculated into the right ES by trans-cranial approach. KLH was found in the ES immediately after KLH challenge and then disappeared on the 7th day. On the 2nd and 3rd day moderate endolymphatic hydrops and a massive cell infiltrations within the ES were observed, and they gradually decreased their severity with time. Diffuse stainings with IgG and C3 were found in the ES, the epithelial and subepithelial regions of the vestibule. Similar findings were obtained in the spiral ligament and the hair cells after antigen challenge. IgG bearing cells were detected within the endolymphatic sac alone. Our results suggested that endolymphatic hydrops may be produced by the imbalance of in-out flow of the endolymph and the immunologically mediated inflammation through IgG-complement system. PMID- 2254812 TI - [A statistical study of clinical cases of malignant tumors first manifested by vocal cord paralysis]. AB - One of the most important problems in dealing with vocal cord paralysis is to clarify the cause of paralysis. In those case where the definite cause is unknown, it is possible that an occult type of malignant tumors exists along the course of the vagus or recurrent laryngeal nerves. For the past 16 years, 62 out of 560 cases with vocal cord paralysis were diagnosed to have malignant tumors first manifested by paralysis of vocal cord. They consisted of 25 cases of thyroid carcinoma, 18 lung carcinoma, 13 esophageal carcinoma, 3 mediastinal tumors and 3 tumors of miscellaneous origin. Among these, 36 were male and 26 were female and the mean age was 63 years old. In 40 cases, paralysis was found on the left side, in 18 on the right and bilaterally in the remaining 4. There was a marked sexual difference in the origin of malignant tumors, i.e. the incidence of lung carcinoma was higher in male with paralysis on the left side, while that of thyroid carcinoma was higher in female. In some cases with thyroid carcinoma, vocal cord paralysis was noted more than a year before the detection of the tumor. Ultrasonography of the neck, chest x-ray, CT scan of the chest, fluoroscopy of the pharyngo-esophagus should be performed for the detection of malignant tumors in cases with left vocal cord paralysis, while ultrasonography of the neck and chest x-ray should be sufficient in right paralysis, although additional fluoroscopy of the pharyngo-esophagus seemed preferable in male. PMID- 2254813 TI - [Hearing and language ability in mild and moderate hearing impaired children]. AB - 102 children (mean age-7 years 9 mo.) with mild and moderate perceptive hearing impairment who had neither any auditory training nor had used a hearing aid were studied. Mean hearing level was 51.9 dB. Our findings: (1) Speech discrimination score (SDS) correlated with the hearing level at 2, 4 and 1 kHz, in that order. In all patients, SDS gradually worsened to 60 dB before registering a sharp decline; SDS was better than in patients who had acute unilateral hearing impairment and similar audiogram patterns, especially in vowels. (2) Correlation existed between the rate of accurate articulation and hearing levels at 2 and 4 kHz; it improved with age but plateaued at around 8 years. In children with a high tone loss, distortion and confusion of fricatives, explosives, unvoiced affricates and postconsonantal vowel /i/ were marked besides articulation errors commonly attributable to normal speech development. (3) On the WISC and WISC-R intelligence scale, verbal intelligence score had little correlation with performance intelligence and was influenced by hearing levels at 2, 4 and 1 kHz, in that order. When the mean hearing level was over 40 dB, verbal intelligence was frequently below par. Performance intelligence grew worse with age. (4) Children with a mild hearing loss exhibited a slight delay in vocalizing the 1st word and combining 2 words together while in those with a moderate loss, the delay in combining 2 words was pronounced. In both mild and moderate hearing loss, verbal intelligence was low when there was a delay in the ability to vocalize two words together. PMID- 2254814 TI - Echinostoma caproni: mating behavior and the timing of development and movement of reproductive cells. AB - The development and movement of reproductive cells were determined in Echinsostoma caproni on autoradiograms by labeling nuclei of stem cells during exposure to [3H]thymidine and then transplanting the worms to mice for various times. The development and movement of sperm, primary oocytes, and vitelline cells were much more rapid in E. caproni than other digenetic trematodes investigated previously. Mating behavior was determined by labeling the sperm of 1 adult by in vitro exposure to [3H]tyrosine and transplanting alone or with unlabeled worms to mice for 4 and 6 days. Echinostoma caproni adults self inseminated when isolated and self- and cross-inseminated when in groups. This behavior is similar to that found for the frog rectal fluke Megalodiscus temperatus but unlike that determined for eyeflukes in the genus Philophthalmus. Worm size was not a barrier to insemination in E. caproni. Cross-insemination could not be detected in 6-day transplants probably because of dilution or elimination of radioactive sperm due to rapid turnover or frequent sperm transfer. An increased number of structural anomalies was noted in the transplanted worms. The most common anomaly was an accumulation of vitelline cells in the vitelline reservoir and ducts. PMID- 2254815 TI - Polymorphism of eimerian oocysts can be a problem in naturally infected hosts: an example from subterranean rodents in Bolivia. AB - Since 1986, 364 tuco-tucos (Ctenomys spp.) representing 7 species were collected from 16 major collecting areas representing at least 4 distinct ecological habitats in Bolivia, South America. All were examined for coccidia, and 125 (34%) had oocysts in their feces including 84 of 236 (36%) Ctenomys boliviensis from tropical palm/savanna habitats; 1 of 3 (33%) Ctenomys conoveri from a chaco thorn forest; 3 of 7 (33%) Ctenomys frater from medium altitude grass habitats; and 6 of 8 (75%) Ctenomys lewisi and 31 of 35 (88%) Ctenomys opimus from high altitude/puna habitats. None of 3 Ctenomys leucodon (high altitude/puna) or 72 Ctenomys steinbachi (tropical palm/savanna) were passing oocysts when examined. The 5 infected host species all had oocysts of Eimeria opimi Lambert, Gardner, and Duszynski, 1988, in their feces. These oocysts and their sporocysts varied greatly in size, both within and between host species, but qualitative characters (e.g., residua and wall texture) remained constant. Our conclusion, that all oocysts seen were E. opimi, was supported by multigroup discriminant analysis of 256 individual oocysts, 30-67 selected randomly from each Ctenomys sp. Minimum polygons enclosing the centroid (= multivariate mean) and the spread of individuals for each species group (OTU) showed significant overlap in discriminant space, and Geisser classification showed a 55% miss rate of individuals being classified into the wrong OTUs. Thus, oocyst and sporocyst lengths and widths cannot be used to separate morphotypes of E. opimi from different Ctenomys spp. from different geographic regions of Bolivia. PMID- 2254816 TI - Morphometric analysis of Psoroptes spp. mites from bighorn sheep, mule deer, cattle, and rabbits. AB - A morphometric study of Psoroptes spp. mites was conducted to address difficulties encountered in species identification and to provide insights into the phylogenetic relationships between mites found on different hosts. A discriminant analysis employing 9 morphologic characters revealed that the lengths of the outer opisthosomal setae and the lateral margins of the opisthosomal knobs were the 2 most important characters for grouping mites according to host species. This analysis clearly separated mites collected from allopatric populations of bighorn sheep, rabbits, and cattle into discrete groups. However, differences were not detected between mites collected from sympatric populations of infested mule deer and bighorn sheep, suggesting that these mites were not host specific and represented a single interbreeding population. Differences also were not detected among mites collected from the ears and body of bighorn sheep and rabbits, demonstrating that the location of mites on a given host should not be used as a primary criterion in species identification. PMID- 2254817 TI - DNA probes distinguish geographical isolates and identify a novel DNA molecule of Babesia bovis. AB - A genomic DNA library of Babesia bovis was screened to identify DNA probe candidates for direct detection of the parasite. Two sequences, Bo6 and Bo25, had the highest sensitivity and further analysis revealed unique characteristics of each of these. Neither sequence hybridized detectably to bovine DNA. Bo6 detected 100 pg of both a Mexican and an Australian isolate of B. bovis, but Bo6 also detected 1.0 ng of Babesia bigemina DNA under identical conditions. A unique characteristic of Bo6 is that it hybridizes to an apparent 7.4-kilobase DNA in undigested genomic DNA of both B. bovis and B. bigemina. The sequence is well conserved between the 2 geographic isolates of B. bovis, but it is apparently divergent in B. bigemina. Bo25 did not hybridize detectably to bovine or B. bigemina DNA. This sequence detected 100 pg of homologous B. bovis Mexican isolate DNA, but the sensitivity was reduced to 1 ng for the Australian isolate DNA. The restriction enzyme profile of the Bo25 sequence in genomic DNA differed markedly in the number, size, and intensity of bands between the 2 B. bovis geographic isolates tested. Thus, the Bo25 sequence can distinguish geographic isolates of B. bovis. PMID- 2254818 TI - Isolation of Trichinella-specific antigens for diagnosis by gradient monoclonal antibody affinity chromatography. AB - Monoclonal antibodies were generated for the isolation of specific antigens from Trichinella spiralis. Two monoclonal antibodies (7G6-2 and 10B6-1) of class IgG2b and IgG1 were selected according to their reactivities in an enzyme-linked immunosorbent assay and western blot. Clone 7G6-2 reacted with an antigen with molecular mass of approximately 60 kDa, and clone 10B6-1 bound to multiple antigens ranging from 49 to 62 kDa on western blot. Antibodies of each clone were purified partially from mouse ascites fluid by ammonium sulfate precipitation and were coupled to CNBr-activated Sepharose 4B. Antigens with molecular masses of 49 kDa and 57 kDa (P49/57), 52-62 kDa (P52/62), and 60 kDa (P60) were isolated from larval excretory-secretory products and crude worm extract with column 10B6-1 and column 7G6-2, respectively, in part by changing the pH of elution buffers. These antigens were mostly glycoproteins, strongly immunogenic, and specific to the parasite. PMID- 2254819 TI - Study of the gametocytocidal/sporontocidal action of qinghaosu (artemisinin) by electron microscopy. AB - The gametocytocidal efficacy of artemisinin (qinghaosu) was evaluated and scanning electron microscopical evidence is given for gametocytocidal action of a single 5-10-mg/kg dose of artemisinin against simian malarial parasite (Plasmodium cynomolgi B). No sporontocidal effect of artemisinin was observed. PMID- 2254820 TI - Structure-activity relationships of benzothiazole and benzimidazole anthelmintics: a molecular modeling approach to in vivo drug efficacy. AB - An investigation of the biochemical effects of an anthelmintic, tioxidazole (TIOX, methyl 6-[n-propoxy]benzothiazole-2-carbamate), on Hymenolepis diminuta in experimentally infected rats is reported. The chemotherapeutic actions of TIOX on H. diminuta in vivo were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TIOX 24 hr earlier were significantly smaller and contained much less glycogen (as a percentage of the wet weight) than worms from untreated controls. In TIOX-treated worms, protein concentrations rose at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TIOX-treated worms were considerably lower than the corresponding control-values. Differences in the absolute amounts of glycogen and protein between control and drug-treated worms were even more pronounced. Administration of a subcurative dose of TIOX to the rat produced in H. diminuta another change, the onset of which preceded the gross alterations in worm weight and chemical composition. In vitro studies, carried out 18 hr after treatment, revealed that TIOX-treated worms absorbed and metabolized much smaller quantities of exogenous glucose than did the controls and that the ability of the worm to accumulate glucose against a concentration difference was significantly depressed. A mode of action common to the structurally related benzothiazole and benzimidazole anthelmintics is indicated by the similarity of their biochemical and physiological effects on the tapeworms and their time course of action when administered to rats infected with H. diminuta. Molecular modeling revealed that the benzothiazole and benzimidazole anthelminitics are congruent electronically and structurally. In vivo drug efficacy depends upon the magnitude of the molecular dipole moment and the percentage of polar surface area. Within the benzimidazole series, structural and electronic congruence is found between the 2 thiazolyl and 2-methyl carbamate groups, suggesting that these groups behave similarly in transport to, and binding at, the active site. Finally, anthelmintics that have the 5' substituents twisted out-of-plane were more active than those anthelminitics with 5' substituents in-plane. All of these factors implicate a highly polar, L-shaped cleft to which the anthelmintics bind at the active site. PMID- 2254821 TI - Susceptibility of wild mammals to infection with Naegleria fowleri. AB - Animals of 4 families of small wild mammals were live-trapped and inoculated intranasally with Naegleria fowleri to determine patterns of susceptibility. Of the 7 species of animals examined, only rodents were susceptible to N. fowleri. Susceptible animals were eastern gray squirrel, hispid cotton rat, muskrat, and house mouse. Mammals that were not susceptible at a dose of 10(6) were opossum, raccoon, and eastern cottontail rabbit. Perhaps rodents and humans share a common anatomical or physiological determinant that makes them susceptible to infection with N. fowleri. PMID- 2254822 TI - Transmammary transmission of mesocercariae of Alaria marcianae (Trematoda) in experimentally infected primates. AB - A lactating primate, Callithrix jacchus, was infected experimentally with 600 mesocercariae of Alaria marcianae 10 days after parturition to determine if she would transmit the mesocercariae to her offspring. Her twin infants were examined 4 wk postinoculation and 16 mesocercariae were found in their tissues. The female was mated again and gave birth to a litter of triplets. She was not given additional mesocercariae. One infant died within hours of birth without suckling and was found negative for any stage of A. marcianae. The other 2 were allowed to nurse for 5 wk, examined and found to be infected with a total of 115 mesocercariae in various tissues, 1 metacercaria in the lungs, and 1 immature and 2 fully formed ovigerous adults in the small intestines. The female was examined at the same time and 246 mesocercariae were recovered. No other stage was found. Histological examination of her mammary glands revealed numerous mesocercariae in the milk-laden alveoli. PMID- 2254823 TI - Relationships between the defensive systems of Iberian-breed swine and the European vector of African swine fever, Ornithodoros erraticus. AB - To discover whether the immune system of Iberian-breed pigs exerts any adverse action on Ornithodoros erraticus, 3 pairs of pigs were subjected to a weekly infestation over 12 wk with 1,000 larvae, 500 nymphs-1, or 200 adults. Each pair was bitten by only 1 developmental stage. Batches of parasites identical to the foregoing ones were fed weekly on control swine. In none of the 10 parameters studied for each of the batches fed weekly was any significant difference found that could be attributed to the state of sensitization of the animals in which, in a previous study, the presence of high titers of anti-O. erraticus antibodies was found. It was observed that the possible pruritus due to immediate hypersensitivity reactions, which in the test animals appeared after the third week, had no protective value in the natural milieu. In view of the inability of the swine to exert any control over the soft ticks, it is concluded that the size of their populations in the pig pens and their composition according to the developmental stage are factors that depend exclusively on the opportunities that swine breeders offer such populations to feed on the animals. PMID- 2254824 TI - Histopathology in hosts parasitized by Sarcoptes scabiei. AB - Histopathologic evaluation of nondermal tissue in rabbits infested with Sarcoptes scabiei var. canis was investigated. Severe infestation resulted in deviant serological and serum biochemical values. Histological study revealed structural changes in the tissues of specific organs. The most prominent histological finding was amyloidosis in the liver, glomerulus of the kidney, red pulp of the spleen, intestines, and tongue. Hosts treated for infestation exhibited no abnormal organ histology. PMID- 2254825 TI - The effects of host diet on Plasmodium yoelii nigeriensis. AB - A comparative study carried out on infected mice to investigate the effect of host diet on Plasmodium yoelii nigeriensis showed that concentrations of blood protein, hemoglobin, and erythrocytes began to decrease in infected mice on day 2 after inoculation and reached the lowest levels on day 8. The greatest decrease was among mice fed on protein-rich mouse cubes, whereas the least decrease was among mice fed on cassava meal. Inflammation of the spleens and livers of infected mice also was noticed. Leucocyte numbers and parasitemia in infected mice reached their peaks on day 8. Again, the greatest prevalence of these abnormalities was apparent among mice whose diet contained the highest amount of protein in comparison to the other diets used in this study. The abnormalities decreased proportionately among the other groups of infected mice, corresponding to the protein content of their various diets. Mice fed on cassava meal, with the lowest content of protein, had the fewest abnormalities. Elevated body temperature, characteristic of severe malaria, and extensive liver damage were highest among mice with the greatest amount of protein in their diet. In view of these observations, it was surmised that during malaria, host diets high in protein heighten the severity of this disease. PMID- 2254826 TI - Lernaeocera branchialis: a potential pathogen to cod ranching. AB - A study was carried out to determine the effect of Lernaeocera branchialis on Atlantic cod infected in the laboratory and in the field and also to ascertain its effect on cod-ranching. Sixty-four percent (308) of 481 cod acquired infections in the laboratory and 33% (159) of the infected fish died over a 4-yr period. About 74% of the deaths occurred within 4 mo of the infection. Monthly samples of cod collected adjacent to a cod-ranching operation showed an initial prevalence of 30% that subsequently decreased in the following 2 mo to 15%. Prevalence of the infection also decreased among the initial field sample of cod that were kept alive, from 30 to 17% during the same 2-mo period and to 9% after 8 mo and was associated with death caused by the parasite. Cod examined at intervals after infection showed evidence of reduced weight gain, lower liver somatic index, liver lipid, and blood values than controls. A field sample taken from the same area during the summer of the following year indicated a prevalence of 12%. This higher than usual prevalence (4-6%) was associated with retention of the intermediate host, Cyclopterus lumpus, that provided an additional source of infective stages. It is likely that increased parasitism could affect the success of the cod-ranching operation in view of the parasite's devastating effects on its hosts. PMID- 2254827 TI - Variations of broncho-alveolar lavage techniques affect cell recoveries. AB - Broncho-alveolar lavage (BAL) has become a routine method of sampling airway and alveolar milieu. Variations of BAL techniques, such as application of chest massage, may have an effect on cell yields. We compared numbers and composition of cells obtained by BAL with and without chest massage from naive rats and from rats infected 7 days earlier with 3,000 larvae of Nippostrongylus brasiliensis. Both techniques revealed significant increases in numbers of agranulocytes and granulocytes after N. brasiliensis infection, but the total yield of cells was 4 5 times greater when massage was used. The use of massage consistently increased the yield of macrophages, but did not result in consistently greater yields of lymphocytes or granulocytes. PMID- 2254828 TI - In vitro maturation of the exoerythrocytic stage of Plasmodium knowlesi observed under phase contrast microscopy. AB - Exoerythrocytic stages of Plasmodium knowlesi were obtained in primary culture of rhesus monkey hepatocytes. The development of a single parasite was followed with phase contrast microscopy until release of merozoites in slightly less than 5 days. This direct observation may offer opportunities to determine visually factors that may influence specific steps of schizont development. PMID- 2254829 TI - Growth of Trichomonas vaginalis in a serum-free McCoy cell culture system. AB - Axenic cultures of Trichomonas vaginalis normally require serum for proliferation, yet serum-containing medium may interfere with the detection of T. vaginalis-secreted virulence factors. Trichomonas vaginalis can, however, grow in coculture with a McCoy cell monolayer in both the presence and absence of serum. For 6 T. vaginalis isolates examined, growth in this serum-free system shows lower peak concentrations of T. vaginalis and longer doubling times than those apparent in a serum-containing McCoy cell system. McCoy cells employed in the system did not appear to secrete soluble growth factors for T. vaginalis. The presence of McCoy cells was required for serum-free proliferation of T. vaginalis possibly indicating that eukaryotic cell membrane components may be important in supporting serum-free growth in this system. PMID- 2254830 TI - Genetic distance and parasite taxonomy. PMID- 2254831 TI - Clinical and microbiological effects of subgingival and gingival marginal irrigation with chlorhexidine gluconate. AB - Recent interest in the local delivery of antimicrobial and anti-inflammatory agents has stimulated interest in the efficacy of various treatment regimens. Chlorhexidine gluconate (CHX) delivered daily by home-applied marginal irrigation as a 0.04% solution in combination with a single professional irrigation of 0.12% CHX was tested over a 3-month period. Sixty periodontal maintenance patients each having at least 2 pockets greater than or equal to 4 mm probing depth, and bleeding on probing were assigned to either Group 1: one professional subgingival 0.12% CHX (Peridex) irrigation (Perio Pik) followed by adjunctive daily home marginal 0.04% CHX irrigation (Pik Pocket); Group 2: one professional subgingival 0.12% CHX irrigation followed by adjunctive daily home marginal water irrigation; Group 3: one professional subgingival water irrigation followed by adjunctive daily home marginal water irrigation; or Group 4: control. At baseline and 3 month visits, subgingival plaque samples were taken from 2 sites per patient. Cultural microbiological analysis was performed using non-selective and selective media. Plaque Index, Gingival Index, pocket probing depths, and gingival recession were assessed. Scaling and root planing (supportive periodontal treatment) was provided for each patient followed by subgingival irrigation as outlined above. At 3 months the Gingival Index and pocket probing depths were both significantly reduced (P less than .05) in all irrigation groups compared to baseline. There were no significant changes in clinical parameters in the control group from baseline to 3 months. In Group 1 the GI was significantly reduced (P less than .05) compared to Group 4 at 3 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254832 TI - Reliability of crevicular fluid measurements taken in the presence of supragingival plaque. AB - The measurement of gingival crevicular fluid (GCF) is commonly used in clinical studies to quantitate the severity of gingival inflammation. This study examined the influence of the presence of supragingival plaque on GCF readings. Bilateral pairs of maxillary premolars received replicate GCF measurements. One of the teeth was randomly selected to be the test tooth. Supragingival plaque was removed from the test tooth between the first and second GCF measurements. Plaque was not removed from the control tooth. The crevicular fluid was collected on filter paper strips which were placed just subgingivally. The quantity of crevicular fluid was determined with the aid of the Periotron 6000. The mean difference between the first and second GCF measurement for the control teeth was -1.5 +/- 5.7 (+/- SD). This change was not significant (P = 0.21). The mean difference between the first and second GCF measurements for the experimental teeth (-21.3 +/- 16.5) was significant (P less than or equal to .001). The mean difference between the control and the experimental GCF differences were found to be highly significant (P less than or equal to .001). The data indicate that the presence of supragingival plaque can significantly elevate the GCF measurements when determined with the Periotron 6000. PMID- 2254833 TI - Control of gingivitis and calculus by a dentifrice containing a zinc salt and triclosan. AB - The effect of unsupervised brushing with a dentifrice containing two antiplaque agents, 0.5% zinc citrate and 0.2% triclosan, on gingival health, plaque, supragingival calculus, and the oral flora was compared to brushing with a non active control dentifrice. Volunteers were given oral hygiene instruction and their teeth were professionally cleaned. They then used a placebo dentifrice for a pre-experimental phase of 1 month, before being stratified into two groups on the basis of their initial plaque, gingival bleeding, and calculus levels, sex, and age. Over the following 6 months, one group used the control while the other used the test dentifrice. Plaque levels, gingival bleeding, and calculus were assessed at baseline and at 3 and 6 months. Supragingival plaque was sampled for microbiological analysis at the initial examination, at 3 and 6 months (conclusion of study period) and 3 months after the study. Representative oral bacteria and the development of bacterial resistance to triclosan were monitored. Results showed that plaque was reduced and gingival health significantly improved during the 1-month pre-experimental period. During the experimental period, this improvement was not maintained by the control group as gingival bleeding and calculus increased. In contrast, gingival bleeding and calculus levels of the test group were maintained significantly below those of the placebo group. Plaque levels were lower in the test group after 3 and 6 months, but the groups were not significantly (P = 0.05) different. No shifts in oral flora or development of bacterial resistance to triclosan were detected. PMID- 2254834 TI - Guided tissue regeneration following treatment of recession-type defects in the monkey. AB - Recent studies have demonstrated extensive amounts of new attachment formation following reconstructive surgery based on the biological principle of guided tissue regeneration (GTR). The aim of the present investigation was to evaluate the effect of using a polytetrafluorethylene (PTFE) membrane in GTR-treatment of recession-type defects and to examine the interrelationship between the PTFE membrane and surrounding periodontal tissues. Full-thickness flaps were raised around 24 maxillary premolar and molar teeth in 6 monkeys. The buccal alveolar bone was surgically removed to a level corresponding to the apical third of the roots. The exposed root surfaces were scaled and planed. In 12 teeth, PTFE membranes were adjusted to cover the exposed root surfaces from a level 1 to 2 mm apical to the CEJ, to a level 3 to 4 mm apical to the alveolar crest. The coronal border of the membranes was tightly adapted to the root surfaces by sling sutures. Twelve teeth served as control teeth without placement of membranes. The flaps were placed with the margin coronal to the CEJ and sutured. The animals were sacrificed after 3 months of healing and all experimental teeth were subjected to histological analysis. The membranes were found to be incorporated with the surrounding connective tissue, and the apical extension of the junctional epithelium terminated at the coronal border of the membranes. The amount of new attachment formation was on the average 74.3% of the defect height in the test teeth, which corresponded to 100% of the membrane covered root portion. Newly formed connective tissue attachment in the controls amounted to an average of 36.9% of the defect height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254835 TI - Efficacy of clindamycin hydrochloride in refractory periodontitis: 24-month results. AB - The purpose of this investigation was to evaluate the use of clindamycin hydrochloride in the treatment of adult refractory periodontitis. Thirty patients with a history of unsuccessful treatment with scaling, periodontal surgery, and the use of tetracyclines were entered into the study. Upon entry, the suspected refractory patients were scaled several times and then monitored for the presence of active disease by probing attachment level measurements performed in duplicate. Active disease was defined as a 3.0 mm or greater loss in attachment from the baseline examination or the occurrence of a periodontal abscess. When active disease was detected, patients were treated with scaling and clindamycin 150 mg qid for 7 days. Patients served as their own controls. Twenty four patients demonstrated further attachment loss following scaling alone and were treated with clindamycin hydrochloride. Scaling and clindamycin treatment decreased the incidence of active disease from an annual rate of 8.0% to 0.5% of sites per patient (P less than .001). The mean time required to detect the first active site increased from 4.9 +/- 3.7 months following scaling alone to 16.7 +/- 7.6 months following scaling and clindamycin (P less than 001). Active sites lost an average of 3.1 mm of probing attachment following scaling alone but "gained" back 2.0 mm at 6 months and 1.5 mm at 24 months post-antibiotic and scaling treatment. Bleeding on probing was significantly reduced (P less than .05) from 31.8% of sites pre-clindamycin treatment to 12.3% at 12 months and 17.9% of sites at 24 months post-clindamycin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254836 TI - The effect of clindamycin on the microbiota associated with refractory periodontitis. AB - The purpose of this investigation was to determine the effect of clindamycin hydrochloride, as an adjunct to scaling, on the microbiota associated with refractory periodontitis and to elucidate the probable causative bacteria associated with the disease. Microbial samples were collected from a subset of 9 patients with severe adult periodontitis who had not responded to conventional treatment modalities including the use of tetracycline and other antibiotics. Microbial samples were collected from a relatively deep site determined to be actively losing attachment and a comparably deep, but quiescent, control site in each patient prior to clindamycin therapy. Samples continued to be collected from the same sites for up to 1 year post-therapy. The microbial flora of each sample were enumerated by darkfield microscopy and predominant cultivable methods. Prior to clindamycin therapy, both active and control sites consisted on average of approximately 50% spirochetes and motile rods and 40% Gram-negative anaerobic rods. Bacteroides intermedius and Porphyromonas gingivalis (formerly B. gingivalis) were elevated in the active, as compared to control, sites and accounted for approximately 20% of the cultured microbiota in the former. Following treatment with clindamycin, the Gram-negative components of the microbiota were either eliminated or severely suppressed. At 1 year post-therapy, spirochetes and motile rods together accounted for about 15% of the microscopic flora. Total Gram-negative anaerobic rods accounted for approximately 20%, and B. intermedius and P. gingivalis combined accounted for less than 2% of the cultured microbiota from historical active sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254837 TI - Gingival manifestations of Wegener's granulomatosis. AB - Localized Wegener's granulomatosis is characterized by necrotizing granulomatous disease affecting the upper and lower respiratory tracts, mucosa, and skin. Without treatment, disseminated necrotizing vasculitis and focal necrotizing glomerulonephritis usually follow. Although oral lesions are relatively common, they have been infrequently described and have rarely been reported as the sole manifestation of this disease. In this report, we present two cases of early Wegener's granulomatosis which featured hyperplastic gingival lesions as the initial presenting lesion. Clinical findings and histological evaluation of tissue obtained from the gingival lesion following incisional and excisional biopsies supported the diagnosis of Wegener's granulomatosis. These cases illustrate that less-frequently occurring entities should be considered in the differential diagnosis of localized gingival lesions which fail to respond to conventional therapy. PMID- 2254839 TI - Putting power into empowerment. PMID- 2254838 TI - Oral manifestation of immunoproliferative small intestinal disease. A case report. AB - A patient with a previous medical history of immunoproliferative small intestinal disease (IPSID) presented with persistent red and ulcerated lesions on her attached gingiva. Despite the obvious long standing gingival inflammation, minimal destruction of alveolar bone had occurred. Following failure of the tissues to respond to routine periodontal therapy, a gingival biopsy was taken. Histological assessment of the specimen revealed several features in common with the intestinal lesions seen in IPSID. In particular, a large plasma cell infiltrate subjacent to the gingival epithelium was noted. There was a marked loss of normal connective tissue morphology and evidence of epithelial degeneration. Treatment has since consisted of palliative measures only. While this is a relatively rare condition, it (as well as other disorders of the immune system) provides a useful insight into the role that the immune system plays in the inflammatory periodontal diseases. PMID- 2254840 TI - Nursing in genetics: current and emerging issues for practice and education. AB - This article focuses on genetics as a dynamic, rapidly expanding health care arena, offering nurses from all specialty areas new career opportunities. Community issues are examined, and the need for nursing research in genetics is identified. A synopsis of a recent national meeting that explored practice changes and the resulting implications for advanced education for nurses in genetics is discussed. Certification remains a controversial issue. Consensus is reached concerning the need to include genetic knowledge at the baccalaureate level. A panel discussion by students and recent graduates describes existing programs in nursing that offer a genetic specialty. PMID- 2254841 TI - Nursing care of the child with a brain stem glioma. AB - The nursing care of the child with a brain stem tumor focuses on supporting the family and the child's adaptation to the physical and emotional problems of an illness with a variable and often fatal course. With the advent of magnetic resonance imaging and stereotaxic biopsy, a more accurate assessment of tumor type, location, and size can be made. Advances in surgery, radiotherapy, and multidrug chemotherapy have affected the course of brain stem tumors even though outcome may remain the same. PMID- 2254842 TI - The effect of home nursing visits on parental anxiety and CPR knowledge retention of parents of apnea-monitored infants. AB - The use of structured home nursing visits was evaluated for its effect upon parental anxiety and retention of cardiopulmonary resuscitation (CPR) knowledge in the family of the apnea-monitored infant. A two-group design was used, with treatment families receiving three visits by the researcher during the 6 weeks postdischarge. Anxiety levels and CPR knowledge of parents were measured at the discharge teaching sessions and again 6 weeks later in both groups. The difference between test scores was evaluated to assess for a treatment effect. Despite no statistically significant difference in anxiety or knowledge over time, the treatment families did show a greater decrease in anxiety scores and maintained or improved their CPR scores. Maternal scores tended to be higher than paternal scores for both variables. There was also some evidence of enhanced parental adaptation to the monitor and to the parental role in the treatment group. PMID- 2254843 TI - Adolescent patterns of communication about the menstrual cycle, sex, and contraception. AB - For this investigation, a sample survey of 179 black women representing 53 family units provided data to examine familial patterns in the amounts of information received about the menstrual cycle, sex, and contraception among adolescent daughters, mothers, and grandmothers; the major source of information about these three topic areas; and the impact of that information on the sexual behavior of adolescent women. Significant relationships were found within the triads (of daughter, mothers, and grandmothers) in the amount of information received about the three topic areas, suggesting familial patterns in the amount of information transmitted intergenerationally. This sample was more likely to report mothers as the source of information on the three topics under study. A significant negative relationship existed between the amount of information received about sex and the experience of a pregnancy before age 18 years among the sample group mothers only. Although this sample received large amounts of information about the menstrual cycle, sex, and contraception from their mothers, the information was ascertained through qualitative responses about the lack of information necessary for sexual health and informed decision-making. The very young mean age (12.3 years) at first intercourse and the low proportion (24.2%) of teenagers using a method of birth control at first intercourse suggested that, intergenerationally, communication about sex and contraception may not be meeting adolescent needs. Consequently, attention should be focused on mothers as agents of sexual socialization of teenagers, and concern must be generated among family planning educators and practitioners for the quality of the information mothers are disseminating about sexually related matters and the impact of that information on the sexual health of teenagers. PMID- 2254844 TI - Choosing (and sticking with) a level of significance. PMID- 2254845 TI - Good news: national standards for child care. PMID- 2254846 TI - Hand-held nebulization therapy. PMID- 2254847 TI - The role of attitudes in memory-based decision making. AB - Frequently, considerable knowledge of the attributes of decision alternatives is available in memory so as to permit a thoughtful and deliberate choice. However, in many instances, individuals neglect to use such knowledge and instead rely on "attitude-based" strategy to make a memory-based decision. The findings from two experiments suggest that as to the motivation to make a correct decision or the opportunity to use the available attribute knowledge decreases, the likelihood that attitudes will guide a memory-based decision increases. The findings illustrate the functional role attitudes play in guiding decisions and behavior. By providing a ready means of evaluating choice alternatives, attitudes enable an individual to make a decision relatively quickly and effortlessly. PMID- 2254848 TI - Differential construal and the false consensus effect. AB - People's own beliefs, values, and habits tend to bias their perceptions of how widely they are shared. The present research examined whether this "false consensus effect" is partly due to people's failure to recognize that their choices are not solely a function of the "objective" response alternatives, but of their subjective construal of those alternatives. Study 1 provided initial support for the importance of differential construal in people's consensus estimates by showing that larger false consensus effects tend to be obtained on items that permit the most latitude for subjective construal. Study 2 replicated this effect experimentally by asking Ss either a general or specific version of the same question. Larger false consensus effects were obtained on the general version that offered more latitude for construal. Studies 3 & 4 provided further support by showing that (a) Ss who made different choices tended to interpret the response alternatives in ways that reflected the choices they made and (b) subjects who were led to construe the alternatives in the same way tended to make the same choices. PMID- 2254849 TI - Contrast and accentuation effects in category learning. AB - This study examines the accentuation of perceived intercategory differences. In Experiment 1, 2 sets of trait adjectives were presented--a neutral set and a set of either favorable traits or unfavorable traits. Ss estimated the mean favorability of each set. The mean favorability of the neutral set was then increased or decreased by adding new traits. As predicted, the estimated mean favorability of the neutral set changed more when the set became more distinct from a contextual set than when it became more similar. In Experiment 2, estimated category means were displaced away from each other (contrast effect), and they moved even farther apart when new information increased the variability of trait favorability (accentuation effect). This change was illusory because the actual category means remained constant. Experiment 3, in which trait adjectives described members of 2 novel groups, replicated Experiment 2. The relevance of contrast and accentuation effects to the development and maintenance of differentiated intergroup perceptions is discussed. PMID- 2254850 TI - Stereotypes and social judgment: the effects of typicality and group heterogeneity. AB - Two experiments showed that when subjects believed a group to be heterogenous, they based their liking for a particular group member on their liking for the group as a whole, independently of and in addition to the target's behavior, and regardless of the target's typicality. When they believed the group to be homogenous, however, they treated the target's typicality as a favorable or unfavorable attribute, which affected their evaluation. The latter subjects used their group stereotype as a standard of comparison in judging the implications of the target's behavior for a trait to which it was relevant. All subjects' stereotypes had a positive influence on judgments of stereotyped-related traits for which the target's behavior was uninformative. A conceptualization is proposed to account for these findings. PMID- 2254851 TI - Long-term impact of parental divorce on optimism and trust: changes in general assumptions or narrow beliefs? AB - Two studies were conducted to examine the long-term impact of parental divorce on beliefs about the self and others. In Study 1, college-aged children of divorce and students from intact families did not differ on 8 basic assumptions or on measures of depression. Those whose parents are divorced, however, were less optimistic about the success of their own future marriages. Assumptions about the benevolence of people best predicted the marital optimism of the parental divorce group, but not of the intact family group. In Study 2, assumptions about the benevolence of people were explored in terms of trust beliefs. College-aged children of divorce and a matched sample from intact homes differed only on marriage-related beliefs, not on generalized trust. Children of divorced reported less trust of a future spouse and were less optimistic about marriage. Exploratory analyses found that continuous conflict in family of origin adversely affected all levels of trust. PMID- 2254852 TI - Hypnotic blindness and the relevance of cognitive style. AB - Real, hypnotized and simulating, unhypnotized subjects were instructed to use either a constructive or a concentrative cognitive style when attempting to respond to a suggestion for hypnotic blindness; also, some subjects were administered the suggestion without any instructions about cognitive style. More reals who received the constructive rather than the concentrative instructions reported complete blindness; a similar number of simulators who received the different instructions reported complete blindness. Moreover, reals who received the constructive instruction reported a more rapidly developed belief in their blindness. The findings are discussed in terms of the relevance of cognitive style to subjects' reports of hypnotic blindness, and the possibility is considered that both reports of and belief in hypnotic blindness are determined in part by cognitive style. PMID- 2254853 TI - Psychological predictors of young adults' drinking behaviors. AB - Path analyses using data from 72 men and 78 women between 22 and 32 years of age compared two models linking personality (conflict resolution styles, intimacy maturity, and occupational identity status) and social roles (family and work status) to young adults' alcohol use. Poor conflict resolution skills and less adult work statuses best accounted for men's excessive drinking, and problems with intimacy best accounted for women's use of alcohol to alleviate emotional distress. In addition, poor conflict resolution skills partly mediated the effects of parent's drinking on son's alcohol consumption. Occupational identity status and intimacy maturity correlated with men's use of drugs rather than men's alcohol use. PMID- 2254854 TI - Resting frontal brain asymmetry predicts affective responses to films. AB - This article assessed whether resting electroencephalographic (EEG) asymmetry in anterior regions of the brain can predict affective responses to emotion elicitors. Baseline EEG was recorded from 32 female adults, after which Ss viewed film clips preselected to elicit positive or negative affect. Resting alpha power asymmetry in the frontal region significantly predicted self-reported global negative affect in response to clips and predicted the difference between global positive and negative affect. Analyses of discrete emotions revealed a strong relation between frontal asymmetry and fear responses to films. Effects were independent of Ss mood ratings at the time at which baseline EEG was measured. Resting anterior asymmetry may be a state-independent index of the individual's predisposition to respond affectively. PMID- 2254855 TI - The ideal self: schematic processing of perfectionistic content in dysphoric university students. AB - This study assessed ideal-self-schematic processing, recall of perfectionistic content rated as not descriptive of the actual self or ideal self, and content specific processing as a function of dysphoria. College students (n = 219) made structural (ST), ideal-self (IS), and actual-self (AS) ratings on perfectionistic, negative, and neutral words, and completed an incidental recall task. Words rated with the IS task were recalled better tha words rated with the ST task, but recall did not differ between the IS and AS tasks. Subjects recalled no-rated perfectionistic words better with the IS and AS tasks than with the ST task. Finally, dysphoric and nondysphoric subjects did not differ in processing specific content. The results support the belief that the IS functions as a schema and suggest that non-self- and non-ideal-self-descriptive perfectionistic content is involved in ideal- and actual-self-schemas. PMID- 2254856 TI - Praise or blame? Affective influences on attributions for achievement. AB - Three experiments showed that mood influences achievement attributions and that cognitive processes underlie these effects. In Experiment 1, happy Ss made more internal and stable attributions for success than failure in typical 'life dilemmas'. In Experiment 2, attributions for real-life exam performance were more internal and stable in a happy than in a sad mood. Dysphoric moods resulted in self-critical rather than self-enhancing attributions, contrary to motivational theories, but consistent with cognitive models and the clinical literature on depression. In Experiment 3 this pattern was repeated with direct self vs. other comparisons, and for self-efficacy judgements. The results are interpreted as supporting cognitive rather than motivational theories of attribution biases. The implications of the results for clinical research, and contemporary affect cognition theories are considered. PMID- 2254857 TI - A method for accurate measurement of cutaneous irritancy of trichothecenes. AB - Conventional skin irritation bioassays for trichothecenes are semiquantitative because test animals vary in sensitivity, and the intensity of cutaneous inflammation is poorly correlated with dose. A quantitative bioassay was therefore devised for toxicological studies on the irritancy of trichothecenes. A graded series of six standard solutions of T-2 toxin (10-60 micrograms/mL) in 2 microL volumes was applied to the shaved skin of young female Wistar rats. Each test sample was applied at least twice to each of five rats. After 48 hours, reactions were rated in units of equivalent concentrations of T-2 toxin, so that measurements were independent of the intensity of inflammatory reaction. Mean concentrations of replicate measurements of test solutions of T-2 toxin between 10 and 60 micrograms/mL were precise (SEM less than 1.6 micrograms/mL) and accurate (within 13% of actual concentrations). PMID- 2254858 TI - Mycotoxin methodology. AB - The development of methods with high specificity and low limits of determination, as well as screening methods that are convenient for detection and rough quantitation of mycotoxins, has proceeded at an accelerating rate over the past few years. Of particular interest has been the widespread application of high performance liquid chromatographic and immunoassay techniques in mycotoxin methodology. An overview of the latest developments in mycotoxin methodology is presented with emphasis on the need for attention to sampling and sample preparation, the basic principles supporting the analytical methodology, the need for techniques to confirm analyte identification, and the requirement for high quality reference materials. PMID- 2254859 TI - Degnala disease in buffaloes and cattle: epidemiological investigations. AB - An attempt was made to identify the epizootiological features associated with Degnala disease occurring in the rice-growing areas of the Indian subcontinent and believed to be associated with mycotoxins. Epizootiological studies were made on disease outbreaks involving 370 herds from 136 villages of Haryana, India, during the years 1968 to 1978. They revealed that the disease, besides being seasonal and regional in occurrence, has a tendency to confine itself to a particular herd or field. All the disease outbreaks occurred during the winter and were associated with the feeding of rice straw. The incidence of the disease, varied from year to year, assuming serious proportions in certain years. The morbidity and mortality rates were 61.61% and 13.93%, respectively, in buffaloes and 13.49% and 2.41% in cattle, with no sex and age differences. Factors such as housing conditions of animals, shape of rice straw stacks, feeding practices, and use of pesticides and fertilizers had no bearing on the occurrence of the disease. Inadequate postharvest drying of rice plants before stacking and stacking at low-lying places or near water channels were the factors identified with occurrence of the disease. In the case of affected herds, 72.07% of the owners stacked rice straw immediately after harvesting, without allowing the plants to dry adequately, versus 10.60% of the owners of unaffected herds. Similarly, 72.97% of the farmers owning affected herds were found to stack rice straw either in low-lying areas or near canals and other water channels, versus 22.73% of the farmers of control herds. PMID- 2254860 TI - Detection and occurrence of cyclopiazonic acid in cheeses. AB - Techniques for detection of cyclopiazonic acid in P. camemberti fermented cheeses are described. They include extraction with CHCl3-MeOH, purification, analysis and quantitation by thin-layer chromatography, and confirmation procedures. Recovery from spiked samples was 75-85%, and the lowest detectable level was 0.02 ppm. This toxic metabolite of P. camemberti was found in the crust of 11 of 20 cheeses of different brands, but not in the inner part. The highest levels were found in three samples: 0.4, 1, and 1.5 ppm. Cyclopiazonic acid doses eventually ingested by a consumer appear to be very low: 3 or 4 micrograms in a portion of the most contaminated sample. PMID- 2254861 TI - Past and future in mycotoxin toxicology research. AB - Before 1960 the toxicology of mycotoxins was mainly of concern to veterinarians, because outbreaks of mycotoxicoses resulted occasionally in considerable loss of livestock. By a wider use of biotests, preferably in mammals, a further decline of such intoxications probably will occur. Following the discovery of the carcinogenicity of some aflatoxins, the focus turned to human health. Screening tests for carcinogenicity are still in development. The test used most frequently is the Ames test on microorganisms. Unfortunately, many problems still must be resolved before an extrapolation of results from these tests to man is possible. Examination of the carcinogenic activity of mycotoxins in long-term animal experiments is often difficult due to lack of resources, lack of test material, and the toxicity of the compounds, which precludes administration of sufficiently high dose levels. The available data regarding a possible carcinogenic activity of several important mycotoxins, such as the trichothecenes or patulin, do not fulfill currently used criteria. Therefore further studies are needed. A new approach is determination of the binding capacity to DNA of suspected carcinogens, which seems to correlate well with carcinogenic potency. By this method, a high carcinogenicity of aflatoxin M1 can be deduced. However, the macromolecular-bound residues of aflatoxin B1, which may occur in tissues of domestic animals, most probably do not show carcinogenic activity. Although many questions are still unanswered, it seems that the numerous mycotoxins identified since 1960 are less toxic or carcinogenic and occur less frequently in food than do aflatoxins. PMID- 2254862 TI - Human exposure to ochratoxin A in areas of Yugoslavia with endemic nephropathy. AB - Ochratoxin A is a mycotoxin with pronounced nephrotoxic potency in all species of single-stomach animals studied; it is a major disease determinant of porcine nephropathy and a disease occurring endemically in several countries. This disease is comparable with Balkan (endemic) nephropathy, suggesting a common causal relationship. Ochratoxin A has been found in foodstuffs in many countries, but the highest frequency of ochratoxin A contamination in foods (10.3% of 1,553 samples of foodstuffs) was encountered in an area of Yugoslavia, where Balkan (endemic) nephropathy is prevalent. Detection of ochratoxin A in human blood samples confirmed the prevalent exposure to this food contaminant. Relative risk calculations indicated a tendency to an association between this mycotoxin and Balkan (endemic) nephropathy, supporting the hypothesis of a causal role of ochratoxin A in this disease. PMID- 2254863 TI - Decontamination and detoxification of mycotoxins. AB - Product decontamination and chemical detoxification are needed because preventive measures are not fully able to avoid contamination by mycotoxins. Criteria for safety evaluation studies of decontaminated products have to be established. Few chemical methods are available on an industrial scale; among them, ammoniation and the mixture monomethylamine-calcium hydroxide treatments show greatest promise of short-term application to oilseed cakes. Technical, economic, and public health aspects of these treatments are considered. Other decontamination techniques are briefly reviewed. PMID- 2254864 TI - Survey of aflatoxin content in Swiss concentrate feeds for dairy cattle. AB - Within the context of restrictive Federal measures, the Swiss concentrate feeds for dairy cattle have been periodically surveyed and analyzed for aflatoxin content. In these commercial feeds, the average aflatoxin B1 content decreased sharply from 47 micrograms/kg in the winter of 1976-1977 (period prior to restrictive measures) to 24 micrograms/kg in the winter of 1977-1978 and to 3 micrograms/kg in the winter of 1978-1979. Work made public by the Federal Office of Public Health, reveals a corresponding downward trend for aflatoxin M1 concentration levels in milk from 109 ng/kg in the winter of 1976-1977 to 44 ng/kg in the winter of 1977-1978 and to 10 ng/kg in the winter of 1978-1979. This record indicates that the feed control measures taken were effective in reducing milk contamination by aflatoxins. PMID- 2254865 TI - Determination of moniliformin by high-performance liquid chromatography. AB - High-performance liquid chromatography (HPLC) was investigated as a technique for determination of moniliformin, a toxic secondary metabolite of various Fusarium species. Two HPLC procedures gave satisfactory results. In the first procedure, separation was achieved on a strong anion exchange column (10 microns, 4 mm id x 25 cm) with an eluting solvent consisting of 0.01 M sodium dihydrogen phosphate (pH 5.0) and a flow rate of 1.0 mL/min. The second procedure made use of paired ion chromatography on a reverse phase column (10 microns, 4 mm id x 25 cm). Elution was done at 2 mL/min with 0.005 M tetrabutylammonium hydrogen sulphate in a mixture containing 8% methanol and 92% 0.1 M sodium phosphate buffer (pH 7.0). Moniliformin was detected in both procedures by ultraviolet absorbance at 229 nm. The lower detection limit of pure moniliformin was 1 ng per injection. Water extraction of moniliformin from dried Fusarium cultures grown on maize was found to be efficient, giving a 95% recovery from a spiked sample. Peak height and retention time reproducibility was good for both procedures. In the analysis of maize containing on the order of 1 mg/kg moniliformin, background interference made interpretation of chromatograms difficult. The cleanup procedure giving the most promising results is described. HPLC methods have been applied successfully in screening fungal cultures for moniliformin production and for monitoring the steps in isolating moniliformin from mold material. PMID- 2254866 TI - Contamination of dairy products by fungal metabolites. AB - The contamination of dairy products with various mycotoxins or other undesirable fungal metabolites can be attributed a.o. to ingestion of contaminated feed or the accidental development of molds and by consequence the excretion of fungal metabolites into the intermediate product. Different dairy products of commercial origin were examined: milk powder, reconstituted infant milk powder, and cheese. In addition to that, environmental factors contributing to the formation of the undesired fungal metabolites were studied. It was found that the presence of mycotoxins in dairy products is more related to the environmental factors causing mold growth on dairy products than to the ingestion of moldy feed by the cow. PMID- 2254867 TI - [Marketing of MRI in the world]. AB - The authors are recalling the main tendancies of the medical imaging world market before studying MRI diffusion in the 3 great sectors, USA, Europe and Japan. MRI diffusion is highly regulated in Europe but in the 2 other areas the growth of MRI was slower than the CT growth for the same period of time for medical, technological and financial reasons. The market evolution with the uprising of the mid-field niche and industrial offers will be presented. PMID- 2254868 TI - [Percutaneous automated lumbar nucleotomy]. AB - The results of percutaneous automated lumbar nucleotomy in the treatment of lumbar disc herniation were assessed in a series of 39 patients. The technique consists of mechanical decompression of the herniated intervertebral disc without total excision. Only one-space discs were treated by this method. Sciatica was the predominant clinical symptom in 30 cases, and lumbar pain in 9 cases. Good to very good results were obtained in 70% of patients with sciatica and in 55% of patients with lumbar pain. After 4 cases of nucleotomy performed after failure of nucleolysis were excluded, the proportion of very good results rose to 77% in sciatica. Conversely, it seems that a number of failed nucleotomies can be treated by nucleolysis. Nucleotomy is very well tolerated and deserves to be used as first-line treatment of single and radiologically well documented lumbar disc herniations. PMID- 2254869 TI - [Fractures of the lateral condyle of the elbow in children. Radiologic aspects]. AB - Fractures of the lateral condyle of the humerus classified as type IV in Salter schema are difficult to diagnose when the capitellum is not ossified. Therefore it is necessary to know exactly the radiological lines which are constructed from the humerus and the radius to the capitellum. Diagnosis is also difficult when the ossification center of the capitellum humeri is only slightly displaced. The epiphyseal fracture line which is always visible at surgery can be missed on X Ray when ossification has not yet appeared. Laminograms are necessary in some cases to be sure that the fracture is displaced. Displaced fractures are always treated by open reduction. PMID- 2254870 TI - [Protrusio acetabuli. An update on the primary and secondary acetabular protrusion]. AB - Acetabular protrusion refers to intrapelvic displacement of the medial wall of the acetabulum and is defined as inward movement of the acetabular line so that the distance between this line and the laterally located ilioischial line is 3 mm or more in adult men and 6 mm or more in adult women. As discussed in this article, acetabular protrusion may be found in many bone disorders such as degenerative joint disease, Paget's disease, rheumatoid arthritis, ankylosing spondylitis, osteomalacia, Marfan's disease and as an effect of irradiation. Protrusio acetabuli appearing in absence of any recognizable cause is termed primary acetabular protrusion or Otto pelvis. Primary acetabular protrusion usually affects both hips in young to middle aged women with a history of diminished abduction, rotation and hip pain since puberty. Radiographically one notes a bilateral axial migration of the femoral head without joint space loss and with moderate degenerative changes. PMID- 2254871 TI - [Radiologic double-contrast aspects of small esophageal cancers. 38 cases]. AB - Double contrast radiological features of thirty eight small esophageal carcinoma are described. Double contrast study is essential in the detection of small esophageal carcinomas: localized thickening of the folds (29%), localized wall stiffness (23.6%), superficial ulcers (13%), discrete superficial nodule (42%), nodularity (15.7%), and ulcerated nodule (15.7%). In our series, six carcinomas arising from reflux esophagitis have the nodular appearance. As in the majority of the cases, small esophageal carcinomas are asymptomatic, when radiologic study of esophagus is performed in patients over 40 years with heavy alcohol and tobacco use, it is imperative to use the double contrast method and to carefully search for minor mucosal abnormalities. PMID- 2254872 TI - [Multiple duodenal lipomas. A x-ray computed tomographic diagnosis]. AB - In a 65-year-old man, upper endoscopy revealed several polypoid lesions into the duodenum, for which histologic examination of the biopsy specimens showed normal mucosa. CT studies demonstrated homogeneous fat density of these nodules, and thus were diagnostic of duodenal lipomas. The diagnosis was ultimately histologically confirmed by deeper peri-endoscopic biopsies. About this case and the some previously reported ones, the authors emphasize the interest of CT examination in this small bowel tumor. PMID- 2254873 TI - [Endorectal Doppler echography of prostate cancer. Potential role in therapeutic evaluation. A case report]. AB - The use of serial transrectal duplex sonography of the prostate in a patient treated for prostatic carcinoma is reported. Pre-treatment transrectal duplex sonography revealed abnormal Doppler signals in the prostate. After multiple agent chemotherapy and bilateral orchiectomy, the prostate volume decreased by 65% and no abnormal Doppler signal could be recorded. Transrectal Doppler sonography of the prostate is expected to provide additional, original data on the response of prostatic tumors to endocrine manipulation or chemotherapy. PMID- 2254874 TI - [Renal tolerance of iodinated low osmolality contrast agents. Clinical and experimental aspects]. AB - The low osmolality iodinated contrast agents (ICA), ionic or non ionic are now suggested too replace the usual high osmolality ICA. The main arguments are the better clinical tolerance and a lower renal toxicity. Recent experimental studies have clearly demonstrated that the low osmolality ICA presents a lower renal toxicity. On the rat, we have confirmed that the in vivo renal toxicity of low osmolality ICA, is lower than the high osmolality ICA toxicity. It is clearly demonstrated on man than the enzyme urinary excretion and proteinuria are little or not modified by the low osmolality ICA, but both are increased by high osmolality ICA. These changes are found with a normal glomerular filtration flow. No difference are noted in the creatinine concentration and clearance follow-up. However it is possible that the necessary population of patient to get statistically significative differences between both agents can be superior to the number of patients studied. In clinical practice, we think, that low osmolality ICA must be used for patients presenting one or several risk factors of acute renal failure. PMID- 2254875 TI - [Evaluation of the role of echography in the positive diagnosis of renal colic secondary to kidney stone]. AB - To evaluate sensitivity and specificity of ultrasound in detecting urinary calculus in renal colic, a prospective study of 31 patients examined by both ultrasound and intravenous urography (IVU) was undertaken. Of the 27 cases of renal colic proved by IVU and/or recovery of a calculus, ultrasound correctly diagnosed urinary calculus in 26 cases with a sensitivity of 96.3%. In the 4 cases in which the sonographic examination demonstrated neither calculi nor unilateral obstruction, further evaluation confirmed the absence of calculi. Specificity of ultrasound was 100%. The results of this study support the use of ultrasound in detecting renal calculus and point out the important place of ultrasound in initial evaluation of renal colic. PMID- 2254876 TI - [Spontaneous dissection of the internal carotid artery with 12th nerve palsy. Radiologic and clinical aspects]. AB - Three cases of 12th nerve palsy due to dissection of the ICA are reported. The clinical and radiological features are described. The useful role played by MRI in the diagnosis is emphasised. PMID- 2254877 TI - GDA-J/F7 monoclonal antibody: a new marker for sperm cell precursors in human semen. AB - Germ cells isolated from semen of oligospermic human donors were found to react with GDA-J/F7 monoclonal antibody (MoAb). Their reactions with this antibody were demonstrated by using fluorescein activated cell sorter (FACS) analysis and indirect immunofluorescence (IIF) test. In the IIF test, the MoAb recognised an antigen on the surface of the sperm cell precursors (SpP) as well as on mature spermatozoa. The specificity of the antibody reaction with the SpP was further confirmed by immunoelectron microscopy. The MoAb did not react with peripheral blood lymphocytes or polymorphonuclear cells but did show cross-reactivity with monocytes. This antibody therefore provides the first marker for the SpP and could be used as a probe for their distinction from leucocytes. This could have clinical application in seminal analysis. PMID- 2254878 TI - Reduction in popliteal lymph node graft-versus-host reactivity by homologous and heterologous pregnancy serum. AB - The popliteal lymph node assay was used to investigate the effect of pregnancy on graft-versus-host reactivity (GvHR) of mouse spleen cells. After local injection of splenocytes from primiparous syngeneically pregnant (by BALB/cJ males) or allogeneically pregnant (by CBA/Ca males) mice no differences in lymph node weight gain were observed in F1 recipients (CBA/Ca x BALB/cJ) when compared to injections of cells from age-matched non-pregnant BALB/cJ mice. However, lymphocytes of pregnant BALB/cJ females which had previously been pregnant between 4 and 6 times by CBA/Ca males induced a significantly lower GvHR compared to cells of matched non-pregnant multiparous mice. These results suggested an inhibitory effect of gestation on cells possibly primed towards paternal antigens by multiple pregnancies. To test this hypothesis, virgin BALB/cJ mice were actively immunized with lymphocytes of male CBA/Ca mice. Before injection into F1 recipients, spleen cells of immunized animals were incubated for 1 h at 37 degrees C in heat-inactivated serum of primiparous pregnant or virgin non pregnant mice. Pre-incubation in pregnancy serum had no effect on unprimed cells, but GvHR of cells derived from immunized donors was significantly depressed in female recipients. In male animals this effect was only irregularly observed. Inhibition of GvHR was also observed with serum from pregnant but not non pregnant pigs. Depression of cellular immune response was observed as early as days 4-9 post-coitum (p.c.) with mouse serum and days 16-19 p.c. with pig serum. These results indicate that pregnancy serum contains factor(s) which modulates the GvHR of primed lymphocytes in both a species- and an antigen-non-specific manner while reactivity of naive spleen cells is not changed. PMID- 2254879 TI - Effects of sperm-reactive antibodies present in human infertile sera on fertility of female rabbits. AB - Sera (n = 19) from immunoinfertile patients were analyzed for cross-reaction with lithium diiodosalicylate (LIS)-solubilized human sperm extract (HSE), protamine and fertilization antigen (FA-1) using an enzyme-linked immunosorbent assay (ELISA). Among the sera tested, 63% reacted with HSE, 58% with protamine and 63% with FA-1. None of the sera from male or female infertile patients was found to contain immune complexes, indicating the antibodies were present in free form. The seven sera that reacted strongest with HSE inhibited human sperm function in sperm penetration of zona-free hamster ova and were associated with fertilization failure in human in vitro fertilization (IVF) technique. The six of these sera that showed binding to rabbit sperm, especially in the head region, also inhibited fertility in female rabbits. Antibodies reactive with FA-1 and not those reactive with protamine reduced fertility in female rabbits. These results indicate that mammalian sperm have several fertilization-related antigens that are evolutionarily conserved. These data also indicate that the rabbit can provide an animal model for studying antibody-mediated human infertility. PMID- 2254880 TI - Demonstration and characterization of HLA-DR positive cells in the stroma of human endometrium. AB - The proportion of stromal cells expressing DR antigens of the HLA system or reacting with an anti-macrophage antibody was studied by immunohistochemical methods in human proliferative, secretory and post-menopausal endometria. DR+ cells showed a rounded morphology with short expansions and represented 13-25% of the stromal cells in the proliferative and 16-43% in the secretory endometrium. The cells reacting with the anti-macrophage antibody were similar to DR+ cells, but their number was between 1/2 and 1/10 of DR+ cells. In the post-menopausal endometria no DR+ cells or elements reacting with anti-macrophage antibody were observed. These results suggest that a significant proportion of endometrial stromal cells expressing type II histocompatibility antigens do not belong to the monocyte-phagocyte system and that their number is under hormonal regulation. PMID- 2254881 TI - Sperm preparation affects reactivity of monoclonal antibodies. AB - The polyacrylamide gel electrophoresis (SDS-PAGE) patterns of extracts prepared from thrice-washed human sperm were compared with extracts of swim-up and non rise sperm. For sperm extraction sodium deoxycholate (DOC), octylphenoxypolyethoxyethanol (NP-40), dithiothreitol (DTT), lithium 3,5 diiodosalicylate (LIS), or 3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate (CHAPS) were used. A pellet of pooled thrice-washed semen was divided and extracted with these detergents. Similar gel electrophoresis profiles, as revealed by silver staining, were observed with the LIS, DOC, NP-40 and CHAPS extracts, whereas DTT extracts lacked the 150 and 200 kDa bands. Different thrice washed semen pools varied in their protein pattern, probably due to the presence of sloughed germinal cells, white blood cells and sloughed cells from the reproductive tract. Swim-up sperm extracts had a different protein profile from that of thrice-washed pools but pools of swim-up sperm had a more constant protein pattern than those of thrice-washed semen pellets. Monoclonal antisperm antibodies did not always recognize antigens of the same molecular weights in western blots when extracts of swim-up sperm versus thrice-washed sperm were compared. In immunoblot studies with monoclonals (produced against thrice-washed sperm, cloned five times, reactive by ELISA and sperm function tests), 4/12 reacted with 0.3% NP-40 extracts of thrice-washed sperm and 5/12 with 0.3% NP-40 extract of swim-up sperm. These findings suggest that definition of antigens by monoclonal antisperm antibodies will be influenced by the nature of sperm extract employed. PMID- 2254882 TI - Northern blot analysis of HLA-G expression by BeWo human choriocarcinoma cells. AB - The BeWo human choriocarcinoma cell line expresses an unusual 41 kDa beta 2 microglobulin-associated class I MHC antigen. HLA-E, -F and -G are known to encode antigens of lower Mr than HLA-A, -B or -C proteins. Using locus-specific probes, we now show that RNA isolated from BeWo cells contains markedly more HLA G transcripts than peripheral blood lymphocytes (PBL), whilst the converse was noted for HLA-B. These results support recent cloning and sequencing data showing the presence of HLA-G transcripts in BeWo cells. PMID- 2254883 TI - Clinical, laboratory and radiographic features in early rheumatoid arthritis. AB - We evaluated disease status in relation to age, sex and disease duration using some short term indices of disease activity, laboratory tests, and radiological features in 315 patients with rheumatoid arthritis of duration varying from 3 to 36 months (mean 12 months). No differences were observed among various age groups in disease duration, female/male ratio, incidence of radiologic lesions and other indices of disease process. Some clinical markers of the disease process such as involvement of the flexor tendons of the hands and Ritchie's index (score greater than 9) were significantly more frequent in the women (p less than 0.0013 and p less than 0.04, respectively). In the patients with disease of recent onset women were slightly more numerous (56%) than men; however, in those with disease duration of 36 months there were significantly more women (72%) (p less than 0.039), suggesting a greater tendency to chronic disease in this sex. Radiological lesions of the small joints of the hands, feet, and/or wrists were found in 37% of the cases with disease duration of up to 4 months and in 91% at 36 months (p less than 0.0001). The lesions were associated significantly more frequently with Ritchie index (p less than 0.02) and with laboratory indices of inflammatory activity (erythrocyte sedimentation rate greater than or equal to 25 mm/h) (p less than 0.001) and immune response (latex test greater than or equal to 80) (p less than 0.0001). Logistic regression analysis showed that the duration of illness is the most important factor correlating with radiologic lesions. PMID- 2254884 TI - Phenotypic characteristics of dissociated mononuclear cells from rheumatoid synovial membrane. AB - The phenotypic characteristics of enzymatically dissociated synovial membrane mononuclear cells from 8 patients (14 samples) with rheumatoid arthritis (RA) were assessed by fluorescence activated flow cytometry and compared to peripheral blood (PB) mononuclear cells from 18 patients with RA and 14 normal controls. There was no significant difference between the percentage of CD4+ and CD8+ lymphocytes in synovial membrane compared to RA and normal PB. Double labelling experiments revealed similar percentages of CD4+ CDw29+ (helper-inducer) and CD4+ CD45R+ (suppressor-inducer) cells in RA and normal PB. In contrast, SM CD4+ CDw29+ cells were present in significantly higher proportions than in RA and normal PB (p less than 0.001). Conversely, synovial membrane CD4+ CD45R+ cells were present in significantly lower proportions than in RA and normal PB (p less than 0.001). A similar pattern of CDw29 and CD45R antigen expression was noted on CD8+ lymphocytes reflecting increased killer-effector (p less than 0.001) and decreased suppressor-effector (p less than 0.001) cells, respectively. Other experiments revealed a significant increase in the percentage of synovial membrane CD20+ cells (B lymphocytes) and HLA-DR+ cells compared to RA PB (p less than 0.02 and p less than 0.001) and normal PB (p less than 0.01 and p less than 0.005), and similar proportions of CD14+ cells (monocytes/macrophages). Our results suggest that RA synovial membrane contains populations of T and B lymphocytes that differ quantitatively and qualitatively from those in PB. These may account for some of the abnormalities in intraarticular humoral and cellular immune responses in patients with RA. PMID- 2254885 TI - Joint inflammation provoked by a local synovial allergic reaction. AB - Homocytotropic antibody was stimulated in animals by administering protein antigens in a vaccine with B. pertussis adjuvant. The titers of the allergic antibody responses were judged by passive cutaneous anaphylaxis reactions. Sera or globulin fractions containing high titers of antibody activity were injected into the knee joints of experimental animals. After sufficient delay for unfixed proteins to be cleared from the knee joints, animals were challenged intravenously with the corresponding antigen. The resultant local reaction of swelling and warmth (passive synovial anaphylaxis) was judged visually and by scanning procedures. Histological studies showed evidence of mast cell degranulation concurrent with synovial reaction. PMID- 2254886 TI - The temporomandibular joint in rheumatoid arthritis. Correlations between clinical and computed tomography features. AB - Clinical and computed tomography (CT) examination of the temporomandibular joint (TMJ) was performed in 26 patients with rheumatoid arthritis (RA) and 26 control subjects. Each examination was scored. In the group with RA 61.2% had physical signs in the stomatognathic system compared to 42.3% in a control group (NS); 88.4% of the group with RA had erosive or cystic lesions of the TMJ compared to 57.6% of control subjects (p less than 0.05). The clinical dysfunction score did not correlate with the CT TMJ score in RA. It correlated with the number of slow acting antirheumatic drugs used, the rheumatoid factor titer and radiographic scores of the hands and cervical spine. In agreement with others, we believe that the only specific CT lesions of RA are erosions and cysts of the mandibular condyle, that there is no correlation between clinical and CT findings of TMJ in RA, and that the intensity of destructive lesions of TMJ on CT in RA is well correlated with the severity of the disease. PMID- 2254887 TI - Adherent synovial cells from nonrheumatoid arthritis do not release interleukin 1 beta and prostaglandin E2 spontaneously in longterm culture. AB - Adherent synovial cells from both 13 patients without rheumatoid arthritis (RA) (gout, osteoarthritis and meniscal lesion) and 8 patients with RA consisted of dendritic cells, macrophage-like cells and fibroblast-like cells after cloning in a similar fashion as reported in our previous paper. All the adherent synovial cells from patients without RA did not release interleukin 1 (IL-1) beta and prostaglandin E2 (PGE2) spontaneously, while those cells released comparable amounts of IL-1 beta, but not PGE2 to RA cells after type II collagen stimulation. Only the synovial cells from RA, irrespective of morphology and cloning, released IL-1 beta and PGE2 without stimulation. Nonrheumatoid synovial cells may differ functionally from RA cells. PMID- 2254888 TI - Defective expression of p70/75 interleukin 2 receptor in T cells from patients with systemic lupus erythematosus: a possible defect in the process of increased intracellular calcium leading to p70/75 expression. AB - Phytohemagglutinin (PHA) stimulated T cells from patients with systemic lupus erythematosus (SLE) showed hyporesponsiveness to interleukin 2 (IL-2) and expressed less p70/75 IL-2R than healthy controls. Ionomycine (IM, calcium ionophore) which selectively upregulated p70/75 expression, induced less p70/75 in patients with SLE than in healthy controls. However, intracellular calcium levels of T cells from patients with SLE increased as much as those from healthy controls, when T cells were stimulated by IM or PHA. Our results suggest that an impaired expression of p70/75 IL-2R in T cells from patients with SLE is not due to a defective calcium influx but to the events after the rise of calcium levels. PMID- 2254889 TI - Anti-RNA polymerase I antibodies in the urine of patients with systemic lupus erythematosus. AB - Urine samples from patients with systemic lupus erythematosus (SLE) (n = 80), patients with rheumatoid arthritis (RA) (n = 21), and healthy controls (n = 36) were analyzed by radio-immunoassay (RIA) for anti-RNA polymerase I (RPI) antibodies. Significant levels of anti-RPI antibodies were detected in the urine of 46% of the patients with SLE but in only 19% of the patients with RA and in no sample from healthy individuals. The presence of anti-RPI antibodies in the urine was confirmed by demonstrating that IgG purified from the urine of patients with SLE was capable of inhibiting the transcriptional activity of RPI in vitro. If the quantity of anti-RPI antibodies excreted is related to disease activity, analysis of urine for these antibodies may be a useful alternative for the purpose of monitoring the progression of disease in individuals with SLE because of the ease by which the sample can be collected. PMID- 2254890 TI - Incidence of polymyositis-dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963-1982. AB - The incidence of hospital diagnosed polymyositis-dermatomyositis (PM-DM) among residents of Pittsburgh and Allegheny County, PA was determined from 1963 to 1982. Medical records of all Allegheny County hospitals were searched for patients diagnosed PM-DM, and each accepted case was reviewed and verified by a physician, according to specified criteria. Direct age adjusted incidence rates were computed for race and sex, as new cases/million population/year, with the 1970 Allegheny County population as the standard. One hundred seventy-seven cases were identified during this 20-year survey for a total annual incidence of 5.5/million population. Incidence more than tripled during 1973-1982 compared to the first decade of study, with the greatest increase occurring in black women. Overall, the female to male incidence ratio was 2.2:1, but during the childbearing years (ages 15-44) this ratio increased to greater than 5:1 in both races. Detection of PM-DM is increasing, as shown by temporal trends. Although our series has significantly more adult PM and less DM and overlap cases than other published studies, annual incidence is similar to that reported in other locales. PMID- 2254891 TI - Prevention of a false diagnosis of sexually acquired reactive arthritis by synovial lymphocyte responses. AB - Three cases are reported in which a diagnosis of sexually acquired reactive arthritis might have been made erroneously from the history, but the enteric origin of the reactive arthritis was evident from synovial lymphocyte responses. The importance of making the correct diagnosis and the avoidance of unwarranted spousal dysharmony is stressed. PMID- 2254892 TI - The spondyloarthropathies in Zimbabwe: a clinical and immunogenetic profile. AB - Spondyloarthropathies are rare in Africa and there is little data regarding HLA association. We prospectively studied 19 patients with spondyloarthropathy, recording clinical details and performing tissue typing (ABC loci). There were 9 patients with ankylosing spondylitis (8 males), all had severe spinal disease but none had ocular or cardiac involvement and HLA-B27 antigen was not found in any of the 7 patients tested; only one patient possessed a B7 crossreacting antigen. The 10 patients with Reiter's syndrome (8 males) had typical clinical features but again the HLA-B27 tissue type was not found. B7-CREG antigen was found in 7 of the 10 patients with Reiter's syndrome. PMID- 2254893 TI - Restricted dose and duration of corticosteroid treatment in patients with polymyalgia rheumatica and temporal arteritis. AB - To analyze whether corticosteroids in low doses during limited time periods could be safely used in the treatment of patients with polymyalgia rheumatica (PMR) or temporal arteritis (TA) the records of 91 patients diagnosed between 1980 and 1987 were reviewed. The mean initial prednisolone dose was in patients with PMR 18 mg/day and the mean duration of treatment was 17 months. In patients with TA the mean initial dose was 31 mg/day and the mean duration of treatment 16 months, and in all the corticosteroid treatment was terminated within 24 months. Patients with coexisting TA and PMR demanded longer treatment compared to patients with either TA or PMR and thus 18/91 patients were treated for more than 2 years. No visual or neurological complications occurred after treatment with corticosteroids had been initiated. Our study indicates that most patients with PMR or TA can be treated safely with an initial prednisolone dose of 10 mg given twice daily. With few exceptions corticosteroid treatment can be terminated within 24 months. PMID- 2254894 TI - Role of membrane proteins in monosodium urate crystal-membrane interactions. II. Effect of pretreatments of erythrocyte membranes with membrane permeable and impermeable protein crosslinking agents. AB - Intact, human erythrocytes were pretreated with membrane permeable, dimethyl adipimidate (DMA) and dimethyl suberimidate (DMS) and membrane impermeable 3,3' dithiobis (sulfosuccinimidylpropionate) (DTSSP) protein crosslinking agents and incubated with monosodium urate monohydrate (MSUM) crystals. The percent inhibition of lysis values for pretreated cells relative to untreated cells were determined. All 3 agents caused a concentration dependent inhibition of MSUM induced hemolysis that was not due to a decrease in MSUM binding to the pretreated membranes. It was proposed that the inhibition of lysis was due to crosslinking of integral and cytoskeletal membrane proteins, resulting in a reduced mobility of the proteins, inhibition of lateralization of integral proteins into aggregates and decreased "pore" formation in the membrane. PMID- 2254895 TI - Pyogenic sacroiliitis in a rural population. AB - We describe 10 cases of pyogenic sacroiliitis occurring in a rural population. Seven were male and 3 were female with a mean age of 22.4 years. None was a recent intravenous drug abuser. Five patients had a history of recent pelvic trauma. 99mTechnetium scintiscans revealed increased sacroiliac (SI) joint uptake in 8 of 8 cases. Blood cultures were positive in 60% of patients. Staphylococcus aureus was isolated in 7 cases from blood and/or SI aspirates and Hemophilus influenzae type B in one case. Nine of 10 patients recovered completely. One underwent arthrodesis for recurrent SI pain without evidence of relapse of infection. Median followup was 18 months. PMID- 2254896 TI - Development and evaluation of a method for preservation of synovial fluid wet preparations for quality control testing of crystal identification. AB - We describe a technique for embedding drops of fresh synovial fluid in mounting resin to prepare test slides that retain crystal morphology for at least 2 weeks. Hospital and private rheumatologists were solicited nationwide to test themselves and their staff with 5 unknown specimens. Eighty-nine percent identified monosodium urate (MSU) crystals from a tophus but only 71% identified smaller and less frequent MSU. Seventy-five percent correctly identified calcium pyrophosphate dehydrate and 42% detected steroid crystals. Apatite crystal clumps included as control slides with no birefringent material were suspected by only 7%. This or another method which simulates actual practice by also testing the equipment and handling of the microscope is proposed as an important component of quality control testing programs for synovianalysis. PMID- 2254897 TI - HLA antigens and nailfold capillary microscopy studies in patients with insulin dependent and noninsulin dependent diabetes mellitus and limited joint mobility. AB - We investigated the HLA status of patients with diabetes associated with limited joint mobility and microvascular complications. An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. HLA antigen DQw1 was detected less frequently in patients with IDDM and was negatively associated with limited joint mobility and retinopathy. Limited joint mobility was significantly correlated with disease duration in IDDM, and was associated with neuropathy in both IDDM and NIDDM and with retinopathy in IDDM. No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. We also investigated the usefulness of nailfold capillary microscopy in a large group of patients with IDDM and NIDDM. Although capillary enlargement and avascular areas were noted in a few patients, nailfold capillary microscopy was not felt to be a useful tool in the evaluation of diabetes. PMID- 2254898 TI - Psychological stress and the fibrositis/fibromyalgia syndrome. AB - The relationship of stress and social support to the fibrositis/fibromyalgia syndrome (FS) was investigated by administration of 4 questionnaire instruments to 28 patients with FS, 20 patients with rheumatoid arthritis (RA) and 28 pain free normal controls. FS showed higher levels of stress as measured by daily "hassles" than did RA or controls. However, on a measure of major life stress, they reported lower levels. No differences were found between groups with regard to daily "uplifts" or social support. Correlations between those measures of stress and social support with their scores on the Arthritis Impact Measurement Scale showed that the Hassles Scale was significantly related to the AIMS Psychological component. PMID- 2254899 TI - Synthesis and release of phospholipase A2 by unstimulated human articular chondrocytes. AB - High activity of proinflammatory, type II phospholipase A2 (PLA2) was found in synovial fluids (SF) in inflammatory arthritis. In search for the sources of this PLA2, we cultured human articular chondrocytes and cartilage explants from healthy, osteoarthritic and rheumatoid joints. All cultures, unstimulated by cytokines, released PLA2 extracellularly. Cultures obtained from the deep layers of the cartilage released more PLA2 than those obtained from the superficial layers. Deep layer explants released 0.38 to 18.16 pmol/min/mg protein PLA2/day, whereas superficial layer explants released 0.39-3.18 pmol/min/mg/day. Chondrocyte cell cultures continuously released PLA2, in the first day 909-46347 pmol/min/(10)6 cells and after 9-26 days of culture 166-2115 pmol/min/10(6) cells. PLA2 released from chondrocytes was calcium dependent and had optimum activity at pH 7.5. Cycloheximide markedly inhibited its release. Chondrocyte cultures also released muramidase (LZM) but there was no correlation between PLA2 and LZM release. It may be concluded that cytokine unstimulated human articular chondrocytes synthesize and release PLA2 extracellularly which is similar to that found in the SF. Thus, chondrocytes may possibly serve as one of the sources of intraarticular PLA2. PMID- 2254900 TI - Characterization of interleukin 1 induced rabbit chondrocyte phospholipase A2. AB - Stimulation of rabbit articular chondrocytes with interleukin 1 (IL-1) results in the activation of intracellular phospholipase A2 (PLA2) and the subsequent secretion of this enzyme into the extracellular milieu. Pretreatment of chondrocytes with actinomycin D or cycloheximide significantly inhibited IL-1 induced PLA2 activation and secretion, suggesting that the enzyme induction process is RNA and protein synthesis dependent. Chondrocyte PLA2 is highly calcium dependent with a 1 mM optimum CA++ concentration for hydrolytic activity; little or no hydrolysis is observed in the absence of calcium and the hydrolytic activity is abolished in the presence of 10 mM ethylenediamine tetraacetic acid. The enzyme is also pH sensitive with optimal PLA2 hydrolytic activity observed at pH 6.5-7. Further, chondrocyte PLA2 was sensitive to inhibition by mepacrine, a compound with PLA2 inhibitory activity. The IL-1 induced chondrocyte PLA2 has a molecular weight of approximately 10 kDa, as determined by molecular sieve G75 column chromatography. The apparent molecular weight and CA++, pH and drug sensitivity of the extracellular and intracellular forms of the IL-1 induced chondrocyte PLA2 are indistinguishable. Since this IL-1 induced enzyme has similar biochemical characteristics to PLA2 enzymes isolated from human rheumatoid and osteoarthritic synovial fluid, we suggest that the chondrocyte may be an important cellular source for this PLA2 enzymatic activity in inflamed joints. PMID- 2254901 TI - Diagnostic criteria for neuropsychiatric systemic lupus erythematosus: the results of a consensus meeting. The Ad Hoc Neuropsychiatric Lupus Workshop Group. AB - Definitions and classifications proposed for the neuropsychiatric complications of systemic lupus erythematosus (NP-SLE) indicate a wide range of approaches taken by different researchers and clinicians. A meeting of investigators was convened to begin a consensus process for standardizing its classification. We found that the level of agreement among raters on the importance of elements to the diagnosis of NP-SLE increased significantly as indicated by an intraclass correlation coefficient of 0.05 before the conference to 0.60 after the conference. The results of such studies can be used to generate and test the utility of diagnostic criteria for NP-SLE in multicenter trials. PMID- 2254902 TI - Diclofenac induced immune thrombocytopenia. AB - We describe a patient with scleroderma who developed immune thrombocytopenia secondary to diclofenac on 2 occasions. Platelet count returned to normal with cessation of diclofenac and institution of prednisone. PMID- 2254903 TI - Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. AB - We describe a fatal case of systemic lupus erythematosus (SLE) developing cerebral and systemic necrotizing vasculitis during pregnancy. The patient was discovered to have SLE at 14 weeks' gestation. Although the symptoms disappeared without treatment with corticosteroid in the 2nd trimester, she presented with meningoencephalitis due to vasculitis in the 3rd trimester. Polyarteritis nodosa (PAN)-like necrotizing vasculitis of the small muscular arteries and arterioles, with acute and healing lesions in the leptomeninges, brain parenchyma and visceral organs was observed at postpartum autopsy. PAN-like vasculitis in the central nervous system is quite rare in SLE. This case is also suggestive in terms of the influence of pregnancy on the activity of SLE. PMID- 2254904 TI - Microscopic Wegener's disease: a particular form of Wegener's granulomatosis. AB - We describe a case of Wegener's granulomatosis in which the disease was manifested with crescentic glomerulonephritis, upper airway ulcerations, and microangiopathic hemolytic anemia with consumptive coagulopathy. No granuloma was identified but antibodies to cytoplasmic components of neutrophils were strongly positive with a diffuse pattern. Because microscopic vessels were predominantly involved (capillaritis), and granuloma were absent, were refer to this particular form of the disease as "microscopic Wegener's disease." PMID- 2254905 TI - Sternocostoclavicular hyperostosis: two cases with differing dermatologic syndromes. AB - Sternocostoclavicular hyperostosis is a rare rheumatic condition characterized by ossification and erosion of the clavicle and the first rib, that has been shown to be associated with pustular skin lesions. We present 2 cases, one of which had features of pustulosis palmaris et plantaris and the other dissecting cellulitis of the scalp. Although the dermatologic manifestations differ, both cases have rheumatologic and roentgenographic features diagnostic of sternocostoclavicular hyperostosis. PMID- 2254906 TI - Yersinia enterocolitica tenosynovitis. The first case. AB - We describe a case of tenosynovitis of tibialis posterior due to Yersinia enterocolitica occurring after injury by a plant thorn in a 55-year-old man. The illness was chronic with 2 recurrences in spite of antibiotic treatment. Full recovery was obtained only after surgical intervention. Our patient's chronic course was fostered by the persistence of thorn fragments in the infected area and the exceptionally pathogenic character of the isolated colony of Yersinia. PMID- 2254907 TI - Septic Streptococcus milleri spondylodiscitis. AB - We describe 2 patients presenting lumbar spondylitis due to Streptococcus milleri. In both cases origin was related to preexistent intestinal pathology. Surgical drainage of a collection of pus was necessary in one case. Longterm antibiotic therapy led to full recovery. Despite confused nomenclature Streptococcus milleri must be considered a serious pathogen mainly associated with purulent infection with osteoarticular affinity. PMID- 2254908 TI - Are emotional stress and heavy muscular exertion measurable variables? PMID- 2254909 TI - Ketoprofen vs naproxen or diclofenac sodium in osteoarthritis. PMID- 2254910 TI - Reflex sympathetic dystrophy; characteristic changes in bone on CT scan. PMID- 2254911 TI - Linear scleroderma and systemic lupus erythematosus. PMID- 2254912 TI - Production of TNF-alpha and IL-1 in active Behcet's disease. PMID- 2254913 TI - Diabetes mellitus in nonhuman primates: recent research advances and current husbandry practices. AB - Primates can be utilized for a variety of studies to give insight into the mechanisms of the onset and progression of diabetes mellitus and obesity, and into the development of secondary manifestations. Results can be used to understand the etiologies and effects of diabetes in human beings. Investigators and animal care personnel should be continually aware of the potential for development of diabetes among primates and should seek to identify the earlier stages before the appearance of overt diabetes. In addition to updating recent research in which nonhuman primates have been used in studies on the different forms of diabetes, this review also furnishes some information about therapeutic management and husbandry of monkeys with predispositions toward diabetes or with overt diabetes. PMID- 2254914 TI - In vitro fertilization in nonhuman primates. AB - Ovulation induction, sperm capacitation, and fertilization have been studied for over 50 years in nonhuman primates but it has only been in the past 20 years that extensive studies on sizeable numbers of embryos have been carried out. Of over 200 species of nonhuman primates only a few have been studied and the majority of the findings come from studies of the squirrel monkey, baboon, rhesus, and cynomolgus macaque. Nevertheless, the fertilization process appears to be similar to that identified in other mammals and in man. PMID- 2254915 TI - Maternal blood pressure and fetal ultrasonography in normal baboon pregnancies. AB - Pregnancy in baboons is characterized by lower systolic, diastolic, and mean blood pressures than in the nonpregnant state. As pregnancy progresses, diastolic and mean pressures tend to increase whereas systolic pressure remains low. Sonographic measurements of fetal growth follow a sigmoid pattern, but their increase in relation to length of gestation approximates a straight line between 6 and 21 weeks of gestation (23 to 84% of term). PMID- 2254916 TI - Morphologic development of the adrenal cortex in squirrel monkeys (Saimiri sciureus). AB - This study describes the morphology of the squirrel monkey (Saimiri sciureus) adrenal gland in the perinatal period. Adrenals of fetal monkeys had a broad central zone of large eosinophilic cells (fetal zone) surrounded by a subcapsular band of small dark cells (definitive zone). Adrenals of stillborn and neonatal monkeys had a reduced fetal zone and an expanded definitive zone that was differentiated into distinct zona fasciculata and zona glomerulosa. By day 18 postpartum, no remnant of the fetal zone remained. PMID- 2254917 TI - Short-term therapy of atherosclerosis with low dose indomethacin: an experimental study. AB - The effects of low dose indomethacin therapy in primary prevention of diet induced atherosclerosis of rhesus monkeys was studied. The parameters studied were serum cholesterol concentration, thromboxane A2 (T x B2), prostacyclin (6 keto-PGF1 alpha) in serum/plasma, and the extent and intensity of coronary atherosclerosis. Although indomethacin did not affect serum cholesterol, it reduced serum T x B2 significantly (P less than 0.01). Plasma 6-keto-PGF1 alpha was not restored to the pretreatment level. A significant protective role of the drug was noted as far as coronary atherosclerosis is concerned (P less than 0.01). PMID- 2254918 TI - Hypercalcemia and disseminated histoplasmosis in an owl monkey. AB - An adult male owl monkey (Aotus nancymai) had hypercalcemia associated with a disseminated case of histoplasmosis (Histoplasma capsulatum var. capsulatum). Histopathologic examination of tissues at necropsy showed moderate to marked numbers of small granulomas involving multiple organs. The granulomas contained numerous round, basophilic, intracellular structures, 1-2 microns in diameter, that stained positive in Periodic acid-Schiff and Gomori's methenamine silver tests. The hypercalcemia in this case was attributed to enhance conversion of dietary vitamin D to 1,25-dihydroxycholecalciferol by the granulomas. PMID- 2254919 TI - A common pentapeptide conformation occurs in viral acid proteases and other proteins. AB - We found a pentapeptide conformation, termed a type I twist, which has a strikingly high propensity (56%) for aspartic acid in the first position. Type I twists include the active site loops from cellular and viral aspartic proteases, with the catalytic Asp in the first position. Fifteen other type I twists, from non-homologous proteins, were found among high-resolution structures in the Protein Data Bank using a comparison method based on main-chain torsion angles. We propose that the Asp affects electrostatic interactions and thus plays a major structural role in the formation of this recurring motif, in addition to its catalytic role in the aspartic proteases. PMID- 2254920 TI - Purification and secondary structure determination of simian immunodeficiency virus p27. AB - We have developed a novel method for the expression and purification of p27, the major core protein of simian immunodeficiency virus. Circular dichroism measurements of purified p27 were used to determine the relative amounts of alpha helix, beta-sheet and unordered secondary structural elements. These empirically determined values appear to be inconsistent with previously published theoretical models based on homology comparisons. PMID- 2254921 TI - Skip residues correlate with bends in the myosin tail. AB - Sharp bends have previously been observed in the tail of the skeletal myosin molecule at well-defined positions 44, 75 and 135 nm from the head-tail junction, and in vertebrate smooth myosin at two positions about 45 and 96 nm from this junction. The amino acid sequence of the heavy chain does not straightforwardly account for such bending on the original model of the tail in which an invariant proline residue is present at the head-tail junction and the repeating seven amino acid pattern of hydrophobic residues lies entirely in the tail. Recently, a revised model has been proposed by Rimm et al. in which the first seven to eight heptads lie in the heads. It is shown here that with this model the observed bends in the tail of skeletal myosin coincide with three of the four additional (skip) residues that interrupt the heptad repeat. It is concluded that the skip residues, by causing localized instability of the coiled-coil, are responsible for the bends. Smooth myosin lacks the second of these skip residues explaining the absence of a bend at 75 nm. PMID- 2254922 TI - Crystallization and preliminary X-ray crystallographic studies of human placental annexin IV. AB - Human placental annexin IV, a member of the annexin family of calcium and phospholipid-binding proteins, has been crystallized by the vapour diffusion method in the presence of calcium, using polyethylene glycol 8000. The crystals are orthorhombic, space C222(1), cell dimensions a = 105.4 A, b = 115.7 A, c = 80.7 A and diffract to at least 2.5 A resolution on a synchrotron source. PMID- 2254923 TI - Structure of a RecA-DNA complex from linear dichroism and small-angle neutron scattering in flow-oriented solution. AB - Small-angle neutron-scattering (SANS) and ultraviolet linear dichroism (l.d.) were measured on identical samples of a RecA-double-stranded (ds) DNA complex, including cofactor adenosine 5'-O-thiotriphosphate, which were aligned by flow in two equivalent Couette devices made of niobium and silica, transparent to neutrons and to ultraviolet light, respectively. The SANS anisotropy indicates a modest orientation of the RecA-dsDNA fiber with the helix axis parallel to the flow field. By correlation with the corresponding l.d. of the DNA at the same orientation conditions, it is inferred that the DNA bases have a local orientation that is approximately perpendicular to the helix axis. By comparison with the worse orientation in single-stranded DNA-RecA, this conclusion suggests that the dsDNA in its complex with RecA is not strand separated, and may be accommodated as an essentially unperturbed, straight double helix running along the RecA polymer fiber. The SANS anisotropy is also found to support the assignment of a subsidiary intensity maximum as originating from the pitch of a helical fiber. PMID- 2254924 TI - Crystallization and preliminary X-ray studies of psophocarpin B1, a chymotrypsin inhibitor from winged bean seeds. AB - Psophocarpin B1 is a 20,000 Mr protein of winged bean (Psophocarpus tetragonolobus) seeds having chymotrypsin inhibitory activity. Single crystals of this protein suitable for X-ray crystallographic studies have been obtained by the vapour diffusion method using ammonium sulphate. The crystals are hexagonal, space group P6(4)22 or P6(2)22, cell dimensions a = b = 61 A, c = 210 A. They are stable to irradiation with X-rays and diffract to at least 2.6 A resolution. PMID- 2254925 TI - Preliminary X-ray analysis of crystals of fasciculin 1, a potent acetylcholinesterase inhibitor from green mamba venom. AB - Fasciculin 1 from Dendroaspis angusticeps has been crystallized by vapour diffusion, in sodium acetate using sodium thiocyanate as precipitant. Tetragonal crystals (space group P4(1)2(1)2 or P4(3)2(1)2) diffract to 1.8 A resolution. The unit cell parameters are a = 40.4 A and c = 81.1 A. We estimated the presence of one molecule in the asymmetric unit. PMID- 2254926 TI - Initiating a crystallographic study of trypanothione reductase. AB - We have obtained well-ordered single crystals of the flavoenzyme trypanothione reductase from Crithidia fasciculata. The crystals are tetragonal rods with unit cell dimensions a = 128.6 A, c = 92.5 A. The diffraction pattern corresponds to a primitive lattice. Laue class 4/m. Diffraction to better than 2.4 A has been recorded at the Daresbury Synchrotron. The accurate elucidation of the three dimensional structure of this enzyme is required to support the rational design of compounds active against a variety of tropical diseases caused by trypanosomal parasites. PMID- 2254927 TI - Characterization and preliminary crystallographic studies on large ribosomal subunits from Thermus thermophilus. AB - Diffracting crystals, suitable for X-ray crystallographic analysis, have been obtained from large (50 S) ribosomal subunits from Thermus thermophilus. These crystals, with P4(1)2(1)2 symmetry and a unit cell of 495 A x 495 A x 196 A, reach typically a size of 0.15 mm x 0.25 mm x 0.35 mm. Using synchrotron radiation at cryo-temperature, these crystals diffract X-rays to better than 9 A resolution, and do not show any measurable decay after a few days of irradiation. They complete a series of crystals, grown by us, from ribosomal particles of the same source, including a 30 S subunits, 70 S ribosomes and complexes of the latter with: (1) an oligomer of 35 uridine residues and (2) the same oligonucleotide together with approximately two Phe-tRNA(Phe) molecules. Crystallographic analysis of the various members of this series should provide information for investigating the conformational changes that take place upon the association of ribosomes from their subunits as well as upon binding of non ribosomal components that participate in protein biosynthesis. PMID- 2254928 TI - Positive and negative regulation of transcription by a cleavage product of Ada protein. AB - The 39,000 Mr Ada protein of Escherichia coli that carries two distinct methyltransferase activities and activity to promote transcription of the ada and the alkA genes is cleaved by a cellular proteinase. As a result, the 20,000 and the 19,000 Mr proteins are formed, which are derived from the N-terminal and the C-terminal halves of the protein, respectively. To elucidate the molecular mechanism of transcriptional control by Ada protein, the N-terminal 20,000 Mr protein was overproduced by manipulating the cloned ada gene. The protein possessed an activity to transfer a methyl group from the methylphosphotriester of the alkylated DNA to its own molecule and retained the potential to promote transcription of the alkA gene. The methylated form of the 20,000 Mr proteins binds to the proper alkA regulatory sequence, as does the intact Ada protein, and facilitates further binding of RNA polymerase to the promoter, thus forming an active transcription initiation complex. The non-methylated 20,000 Mr protein was incapable of binding itself or supporting RNA polymerase binding to the alkA promoter. When the 20,000 Mr protein was produced under the control of the lac promoter in E. coli and then exposed to a methylating agent, a considerable amount of 3-methyladenine-DNA glycosylase II, the product of the alkA gene, was formed. Thus, the results obtained in in vitro experiments were confirmed by the events observed in vivo. The methylated 20,000 Mr protein also binds to the ada promoter; however, it does not facilitate further binding of RNA polymerase to the promoter nor does it promote ada transcription in vitro. These findings indicate that the N-terminal half of Ada protein is mainly responsible for recognition of and binding to alkA and the ada regulatory sequence. The methylated 20,000 Mr protein occupies the same region of the ada promoter to which the intact Ada protein would bind, thereby suggesting that it acts as a repressor for expression of the ada gene. The ada transcription promoted by the Ada protein was greatly inhibited by the methylated, but not the non-methylated, form of the 20,000 Mr protein. In an in vivo system, formation of the 20,000 Mr protein leads to inhibition of transcription from the ada promoter. We suggest that termination of the adaptive response may come about by proteolytic cleavage of the Ada protein, the result being a loss of the activator as well as formation of the repressor for ada transcription. PMID- 2254929 TI - Specific sequences downstream from -6 are not essential for proper and efficient in vitro utilization of the Escherichia coli lactose promoter. AB - A series of deletion mutants of the wild-type Escherichia coli lactose promoter, with endpoints at +25, +19, +14, +1 and -6 (relative to the start of transcription at +1), was constructed and the deleted DNA replaced with non-lac DNA. These mutants were used to show that no specific DNA sequences downstream from -6 are required for efficient promoter utilization in vitro. In all cases transcription is dependent on the presence of the catabolite activator protein (CAP) and cAMP, and begins at +1 at a level indistinguishable from that at the wild-type promoter. A set of lac DNA fragments deleted to -6 was constructed, having an A, C, G or T residue at +1 and heterologous DNA downstream. These synthetic promoters allow systematic testing of the effect of the initiating nucleotide on the transcription process. Again, transcription occurs mainly from +1, at a level similar to the normal wild-type level. No substantial differences between these promoters are observed in the rates of formation of stable complexes, in the degree of complex formation, in the rate at which polymerase "escapes" from the complex or in abortive transcription products. Equivalent results are seen with a related set of constructs based on the CAP-insensitive lac UV5 promoter. Thus, lac promoter sequences including consensus hexamers at 10 and -35, plus the spacer region between them, provide specificity and efficiency both in initiation of transcription by RNA polymerase and in CAP polymerase interactions. A question as to whether there is a third RNA polymerase binding site at lac, in addition to the known overlapping P1 and P2 regions, was not unambiguously answered. However, if a "P3" site does exist, it must lie between P1 and P2. Alternatively, the variety of polymerase interactions at wild type lac may reflect different structural states of the enzyme. The results presented here indicate that DNA downstream from -6 plays little part in determining the conformation of the enzyme at the lactose promoter. PMID- 2254930 TI - FLP protein of 2 mu circle plasmid of yeast induces multiple bends in the FLP recognition target site. AB - The FLP recombinase of the 2 mu plasmid of Saccharomyces cerevisiae binds to a target containing three 13 base-pair symmetry elements called a, b and c. The symmetry elements b and c are in direct orientation while the a element is in inverted orientation with respect to b and c on the opposite side of an eight base-pair core region. Each symmetry element acts as a binding site for the FLP protein. The FLP protein can form three different complexes with the FLP recognition target (FRT site) according to the number of elements within the site that are occupied by the FLP protein. Binding of FLP to the FRT site induces DNA bending. We have measured the angles of bends caused by the binding of the FLP protein to full and partial FRT sites. We find that FLP induces three types of bend in the FRT-containing DNA. The type I bend is approximately 60 degrees and results from a molecule of FLP bound to one symmetry element. The type II bend is greater than 144 degrees and results from FLP molecules bound to symmetry elements a and b. The type III bend is approximately 65 degrees and results from FLP proteins bound to symmetry elements b and c. Certain FLP proteins that are defective in recombination can generate the type I and type III bends but are impaired in their ability to induce the type II bend. We discuss the role of bending in FLP-mediated recombination. PMID- 2254931 TI - Escherichia coli threonyl-tRNA synthetase and tRNA(Thr) modulate the binding of the ribosome to the translational initiation site of the thrS mRNA. AB - Escherichia coli threonyl-tRNA synthetase binds to the leader region of its own mRNA at two major sites: the first shares some analogy with the anticodon arm of several tRNA(Thr) isoacceptors and the second corresponds to a stable stem-loop structure upstream from the first one. The binding of the enzyme to its mRNA target site represses its translation by preventing the ribosome from binding to its attachment site. The enzyme is still able to bind to derepressed mRNA mutants resulting from single substitutions in the anticodon-like arm. This binding is restricted to the stem-loop structure of the second site. However, the interaction of the enzyme with this site fails to occlude ribosome binding. tRNA(Thr) is able to displace the wild-type mRNA from the enzyme at both sites and suppresses the inhibitory effect of the synthetase on the formation of the translational initiation complex. Our results show that tRNA(Thr) acts as an antirepressor on the synthesis of its cognate aminoacyl-tRNA synthetase. This repression/derepression double control allows precise adjustment of the rate of synthesis of threonyl-tRNA synthetase to the tRNA level in the cell. PMID- 2254932 TI - Stoichiometry of elongation factor G function in translation. AB - A steady-state translation system has been used in vitro to measure the stoichiometry with which elongation factor G-GTP complexes are dissipated during polypeptide elongation. It has been possible to separate this dissipation from that associated with elongation factor Tu function. Our measurements for the wild type as well as for two mutant variants indicate that there is one elongation factor G-GTP complex dissipated per peptide bond in the steady-state. PMID- 2254933 TI - Localization of the proteins gp7, gp8 and gp10 in the bacteriophage T4 baseplate with colloidal gold: F(ab)2 and undecagold: Fab' conjugates. AB - We report the localization of the proteins gp7, gp8 and gp10 in the bacteriophage T4 baseplate. Proceeding on the assumption that these proteins occupy discrete locations, we have decorated baseplates and tails with immunological probes. Using 5 nm diameter colloidal gold: F(ab')2 conjugates, we show that proteins gp7 and gp10 are located directly at the vertex, with gp10 positioned in the pin directly below gp7. gp8 is located beside gp7 towards the centre of the baseplate. Using a novel undecagold: Fab' conjugate we have also determined the radial positions of gp7 and gp8 in baseplates that have transformed to stars. A mechanism for the nature of the hexagon-to-star transformation is proposed. PMID- 2254934 TI - Structural study of the yeast RNA polymerase A. Electron microscopy of lipid bound molecules and two-dimensional crystals. AB - Two-dimensional crystals of yeast RNA polymerase A (I) were obtained by interaction with positively charged lipid layers. The analysis of single molecular images of lipid-bound RNA polymerases showed that the enzyme was preferentially oriented by the lipid phase, which probably facilitated crystallization. Electron micrographs of the crystals revealed a rectangular unit cell 25.8 nm by 45.6 nm in size containing four RNA polymerase dimers related by P22(1)2(1) symmetry. The projection map showed, at about 2.5 nm resolution, two different views of the enzyme characterized by two bent arms, which appeared to cross at one end. These arms are likely to contain the A190 and A135 subunits and delimit a 3 to 4 nm wide groove. Additional structural features were observed and compared to the Escherichia coli enzyme. PMID- 2254935 TI - Co-operative interactions between the catalytic sites in Escherichia coli aspartate transcarbamylase. Role of the C-terminal region of the regulatory chains. AB - In aspartate transcarbamylase (ATCase) each regulatory chain interacts with two catalytic chains each one belonging to a different trimeric catalytic subunit (R1 C1 and R1-C4 types of interactions as defined in Fig. 1). In order to investigate the interchain contacts that are involved in the co-operative interactions between the catalytic sites, a series of modified forms of the enzyme was prepared by site-directed mutagenesis. The amino acid replacements were devised on the basis of the previously described properties of an altered form of ATCase (pAR5-ATCase) which lacks the homotropic co-operative interactions between the catalytic sites. The results obtained (enzyme kinetics, bisubstrate analog influence and pH studies) show that the R1-C4 interaction is essential for the establishment of the enzyme conformation that has a low affinity for aspartate (T state), and consequently for the existence of co-operativity between the catalytic sites. This interaction involves the 236-250 region of the aspartate binding domain of the catalytic chain (240s loop) and the 143-149 region of the regulatory chain which comprises helix H3'. PMID- 2254936 TI - Situations of gamma-turns in proteins. Their relation to alpha-helices, beta sheets and ligand binding sites. AB - Gamma-turns occur as one of two possible enantiomers with regard to their main chain structure, called classic and inverse. Of these, inverse ones are more common. Unlike other hydrogen bonds, those in inverse gamma-turns include a large proportion that are weak. If such hydrogen bonds are included, these turns may be said to be abundant in proteins. A significant number of inverse gamma-turns, usually weak ones, exist as consecutive turns in a structural feature, now called the 2.2(7)-helix, proposed for polypeptides as long ago as 1943 by Huggins. Most of these features occur within strands of beta-sheet. The less-weak inverse gamma turns fall into several structural subgroups. They are frequently situated directly at either end of alpha-helices or of strands of beta-sheet, or adjacent to certain loop motifs. In general, they are well conserved during evolution and some are found at key positions in proteins. One occurs in the first hypervariable loop in the heavy chain of immunoglobulins. PMID- 2254937 TI - Crystallographic study at 2.5 A resolution of the interaction of methionyl-tRNA synthetase from Escherichia coli with ATP. AB - The crystal structure of the tryptic fragment of the methionyl-tRNA synthetase from Escherichia coli, complexed with ATP, has been refined to a crystallographic R-factor of 0.220, at 2.5 A resolution (for 4433 protein atoms). In the last stages of the refinement, the simulated annealing refinement method was fully applied, contributing to a drastic improvement of the model and the identification of the missing atoms. In the final model, the root-mean-square deviation from ideality for bond distances is 0.021 A and for angle distances is 0.054 A. The position of the zinc ion has been confirmed and is located near the active site. The tryptic fragment is composed of two globular domains. The first domain, from the N terminus to Thr360, contains a nucleotide-binding fold into which two long polypeptides of 101 and 70 residues are inserted. The nucleotide binding fold is strengthened by the presence of the zinc ion in the vicinity of the active site. The second domain, up to Pro526, is mainly alpha-helical. The C terminal polypeptide, Phe527 to Lys551, folds back towards the first domain, making a link between the two domains. The heptapeptide 528-534 partly shapes a deep cavity that plunges into the central core of the nucleotide-binding fold, where the ATP molecule is located. The adenine ring, deeply buried in the bottom of the cleft, is blocked between the first helix HA, and the strands A and D of the beta-sheet and makes no polar interaction with the enzyme. The 2' and 3' hydroxyl groups of the ribose, whose conformation is C2' endo, interact with the main-chain carbonyl oxygen atoms of Ile231 and Glu241, respectively. The side chain nitrogen atom of Lys142 is at hydrogen-bonding distance from the ring oxygen O-4' of the ribose. One of the alpha-phosphate oxygen atoms and one of the gamma-phosphate oxygen atoms interact with the imidazole ring of His21, which is well conserved in many of the known synthetases; this indicates a possible crucial role for this residue in binding ATP. The beta-phosphate group is linked to the main-chain carbonyl oxygen atom of Tyr15 through an intermediate water molecule. The gamma-phosphate group interacts with the carbonyl oxygen atom and the side-chain of Asn17.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2254938 TI - Structure of an engineered porcine phospholipase A2 with enhanced activity at 2.1 A resolution. Comparison with the wild-type porcine and Crotalus atrox phospholipase A2. AB - The crystal structure of an engineered phospholipase A2 with enhanced activity has been refined to an R-factor of 18.6% at 2.1 A resolution using a combination of molecular dynamics refinement by the GROMOS package and least-squares refinement by TNT. This mutant phospholipase was obtained previously by deleting residues 62 to 66 in porcine pancreatic phospholipase A2, and changing Asp59 to Ser, Ser60 to Gly and Asn67 to Tyr. The refined structure allowed a detailed comparison with wild-type porcine and Crotalus atrox phospholipase A2. The conformation of the deletion region appears to be intermediate between that in those two enzymes. The residues in the active center are virtually the same. An internal hydrophobic area occupied by Phe63 in the wild-type porcine phospholipase A2 is kept as conserved as possible by local rearrangement of neighboring atoms. In the mutant structure, this hydrophobic pocket is now occupied by the disulfide bond between residues 61 and 91. A detailed description of the second binding site for a calcium ion in this enzyme is given. PMID- 2254939 TI - Machine learning approach for the prediction of protein secondary structure. AB - PROMIS (protein machine induction system), a program for machine learning, was used to generalize rules that characterize the relationship between primary and secondary structure in globular proteins. These rules can be used to predict an unknown secondary structure from a known primary structure. The symbolic induction method used by PROMIS was specifically designed to produce rules that are meaningful in terms of chemical properties of the residues. The rules found were compared with existing knowledge of protein structure: some features of the rules were already recognized (e.g. amphipathic nature of alpha-helices). Other features are not understood, and are under investigation. The rules produced a prediction accuracy for three states (alpha-helix, beta-strand and coil) of 60% for all proteins, 73% for proteins of known alpha domain type, 62% for proteins of known beta domain type and 59% for proteins of known alpha/beta domain type. We conclude that machine learning is a useful tool in the examination of the large databases generated in molecular biology. PMID- 2254940 TI - The entropic tension of protein loops. AB - A large survey of reliably known structures supports the hypothesis that protein loops can behave like elastic strings, and has enabled a parameter describing the entropically generated tensions to be determined. Such tensions may be of major importance in the folding process; here they are discussed mainly in the context of the final collapse of a molten globule into the native structure, though they must also play a dominant role in the earlier development of the tertiary fold. PMID- 2254941 TI - Endocrine cells and brush cells at the bronchiolo-alveolar junctions of neonatal Syrian hamster lungs. AB - Endocrine cells and brush cells at the bronchiolo-alveolar junctions of the lung of neonatal hamsters were studied by transmission electron microscopy. On both sides of the junctions (bronchiolar and alveolar), clusters of endocrine cells occur as neuroepithelial bodies (NEB). A few solitary endocrine cells are also present at the alveolar sides of the junctions. Some endocrine cells reach from the basement membrane to the air space but the area of apical cell membrane exposed to the airway is small as the cells are largely covered by Clara cells in the bronchioles and by thin attenuations of alveolar type 1 cells in the alveoli. Some Clara cells around NEB contain cytoplasmic lamellar bodies, similar to those characteristically associated with alveolar type 2 cells. A few brush cells are also seen at both sides of the junctions. Long wide microvilli with filamentous cores extend from the apices of the brush cells. Endoplasmic reticulum and Golgi apparatus are moderately developed. Well-developed bundles of intermediate filaments course throughout the cytoplasm of some of the brush cells. The functions of endocrine cells and brush cells are unknown. However, the presence of these cells at the bronchiolo-alveolar junctions of neonatal hamster lungs suggests a role in regulation of respiratory function. PMID- 2254942 TI - Functional morphology of dewlap extension in the lizard Anolis equestris (Iguanidae). AB - The dewlap is an extendible flap of skin ordinarily folded under the throat. Lizards, particularly those in the genus Anolis, extend their dewlaps during interactions with conspecifics, other lizards, and potential predators. Dewlap extension is effected by movements of elements of the hyoid apparatus. This paper describes the anatomy of the hyoid and associated musculature in Anolis equestris, a large arboreal lizard with a prominent dewlap. A mechanism for dewlap extension is proposed based on results of morphological and experimental techniques. Specializations of the hyoid skeleton for dewlap extension include elongated second ceratobranchials and highly movable joints between the ceratohyals and the hypohyals and between the first ceratobranchials and the body of the hyoid. A well developed M. ceratohyoideus extends between the ceratohyals and the first ceratobranchials of the hyoid apparatus. During dewlap extension, the hyoid apparatus acts as a first order lever. Contraction of M. ceratohyoideus pulls the ceratohyals posteriorly causing the hypohyals and the body of the hyoid to rotate dorsally around the first ceratobranchial/body joints. This movement results in the second ceratobranchials swinging forward and down, unfolding the dewlap. The relative immobility of the first ceratobranchials provides stability to the hyoid apparatus during dewlap extension. A comparison is made of dewlap extension and other hyoid displays. PMID- 2254943 TI - Introduction to diagnostic ophthalmic ultrasound for nurses in ophthalmology. AB - Ophthalmic nurses are performing a variety of technical tasks, one of which is performing ultrasound to determine axial lengths. Indications for performing ophthalmic ultrasound fall into five categories: opaque media, intraocular masses, biometry, retrobulbar masses, and foreign bodies. Increased knowledge facilitates the ability to recognize abnormalities that may be apparent when performing ultrasonography, as well as to provide the patient with thorough explanations and information. PMID- 2254944 TI - The EyeCare Group: a volunteer support group for cataract patients. AB - Although cataract surgery is a common procedure, the first-time patient often feels intense anxiety before the operation. The EyeCare Group is made up of former cataract patients who provide support to patients. In starting a support group, ask the physicians for recommendations for volunteers, provide orientation, enable volunteers to share joys and concerns with other volunteers, and provide continuing education and support for the volunteers. PMID- 2254945 TI - Sensory supports for the visually impaired. AB - Because patients are spending less time in the hospital, nurses must use specific techniques to address visual loss and assist low-vision patients with discharge planning. A majority of low-vision patients can distinguish the color red; this can be used to code the tops of medication bottles. When speaking to a low-vision patient, talk softly and teach information in accordance with the patient's comprehensive ability. Attending to the tactile sense should be incorporated into daily care. PMID- 2254946 TI - Reflecting on old Olympus' towering tops. AB - Mnemonics are useful tools for memorizing factual information. "On old Olympus' Towering Tops, a Finn and German viewed some hops" is a way to remember the 12 cranial nerves. The 12 cranial nerves, in order, are olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, auditory, glossopharyngeal, vagus, sensory (accessory), and hypoglossal. PMID- 2254947 TI - Developing printed materials for patients with visual deficiencies. AB - In preparing educational materials for patients with vision deficiencies, nurses must take into consideration type size, typeface, and color. Patients surveyed preferred 14-point, sans serif type. Black type on white paper was also preferred. Collaboration between the nurse and the graphic designer will help ensure that the printed material will be understandable to the target group. PMID- 2254948 TI - Melanocytoma. PMID- 2254949 TI - Helpful gadgets for the contact lens technician. PMID- 2254950 TI - Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey. AB - Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing. PMID- 2254951 TI - Effects of skin preapplication treatments and postapplication cleansing agents on dermal absorption of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats. AB - Various methods of preparing dermal application sites in Fischer 344 rats prior to exposure to 2,4-dichlorophenoxyacetic acid dimethylamine salt (2,4-D amine) and the effect of various cleansing agents following exposure were examined by measuring recoveries of 14C-labeled 2,4-D amine in skin, postapplication cleansing solution, blood, and urine. The middorsal area of the rat was the site of application for four treatments tested: (1) hair clipping only, (2) hair clipping followed by an epilatory cream, (3) hair clipping plus shaving with an electrical razor, and (4) as in treatment 3 followed by washing with soap and water. A last preparation was the rat's tail thoroughly brushed with soap and water. The results indicated that the tail retained greater than 75% of the material, thus preventing its absorption into the blood stream and subsequent removal by cleansing. With treatment 1 the dense short hair remaining after clipping impaired the absorption of 2,4-D as evidenced by considerably lower blood and urinary levels than treatments 2-4. With preparations 1-4, 45-61% of the dose was removed with the 7-h postapplication cleansing and a further 5-6% with the subsequent 23-h cleansing. In other studies using preparation 3 above, the following cleansing agents were tested: soap and water, water, isopropanol, acetone, and Rad-Con, a foam-producing cleanser. Rad-Con removed more 2,4-D from the skin than other cleansing agents after 7 h of exposure and more than soap and water after 23 h. The percentages of 2,4-D left on the skin following either 7- or 23-h cleansing with Rad-Con were 8-12%, nearly half those following the other cleansing agents. Cleansing agents other than Rad-Con presented little advantage over soap and water. With all cleansing agents, delaying cleansing from 7 to 23 h after exposure resulted in higher blood and urinary levels of 2,4-D measured 24 h after application. PMID- 2254952 TI - Potentiation of organophosphorus-induced delayed neurotoxicity by phenylmethylsulfonyl fluoride. AB - It is well known that pretreatment with the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF) can protect experimental animals from organophosphorus-induced delayed neurotoxicity (OPIDN), presumably by blocking the active site of neurotoxic esterase (NTE) such that binding and "aging" of the neuropathic OP is thwarted. We report here that while PMSF (60 mg/kg, sc) given 4 h before the neuropathic organophosphate (OP) mipafox (50 mg/kg, im) completely prevented the clinical expression of OPIDN in hens, the identical PMSF treatment markedly amplified the delayed neurotoxicity (relative to hens treated with OP only) if administered 4 h after mipafox (5 or 50 mg/kg, im). Moreover, in a separate experiment using diisopropylphosphorofluoridate (DFP) as the neurotoxicant in place of mipafox, posttreatment with PMSF 4 h after DFP (0.5 mg/kg) also accentuated the severity of ataxia. These data indicate that PMSF only protects against OPIDN if given prior to exposure to the neurotoxicant; treatment with PMSF after OP exposure critically exacerbates the delayed neurotoxicity from exposure to organophosphorus compounds. PMID- 2254953 TI - Microtubule associated protein (MAP1B) is present in cultured oligodendrocytes and co-localizes with tubulin. AB - Differentiation of oligodendrocytes is accompanied by the extension of processes and the assembly of the myelin membrane. It is likely that the cytoskeleton plays an important role in this process in terms of changes in cell shape, transport of myelin components, and organization of the myelin membrane. Oligodendrocytes contain microtubules (MT) which associate with other components of the cytoskeleton, and microtubule associated proteins (MAPs) may mediate some of these interactions. In this study we have shown the presence of MAP1B in oligodendrocytes grown in primary glial cultures by double-label immunofluorescence using antibodies to galactocerebroside (GC) and MAP1B. The staining of the cultures showed that GC-positive oligodendrocytes were also stained with MAP1B antibodies. However, MAP1B stain was limited to cell bodies and processes, whereas GC stain was also seen in flattened membrane sheets and punctate staining in processes. MAP1B staining was also compared with that of myelin proteolipid (PLP), myelin basic protein (MBP) and beta-tubulin in secondary glial cultures that were enriched for oligodendrocytes. The results showed a typical staining of cell bodies and membranous profiles using PLP antibodies, and the staining of cell bodies and flattened regions of membranous sheets by MBP antibodies. In contrast, both polyclonal and monoclonal antibodies to MAP1B showed a uniform diffuse staining of cell bodies, major processes, and fine interconnected processes. Double-labeling of the cells showed that MAP1B was co-localized with tubulin, but was not present in glial fibrillary acidic protein (GFAP)-positive astrocytes. Western and Northern blot analyses of primary glial cultures showed that MAP1B had a molecular mass of 320 kDa and a mRNA of 10 kb. These values are identical to those previously reported for brain MAP1B (Safaei and Fischer, 1989) and demonstrate the presence of MAP1B in oligodendrocytes. PMID- 2254954 TI - Establishment of a permanent rat brain-derived glial cell line as a source of purified oligodendrocyte-type 2 astrocyte lineage cell populations. AB - A permanent glial cell line (L3) has been established from mixed glial cultures obtained from neonatal rat forebrain by repetitive passaging and selection of the process-bearing cells growing on top of a flat cell monolayer. Continuous propagation of the process-bearing cells was supported by the flat cells, of presumed astroglial origin, which were present in negligible amounts following each passage but then grew and formed a basal, feeder layer. Throughout a culture period of over 2 years, the L3 cells have maintained a stable morphological and antigenic phenotype. In serum-containing culture medium, most of the process bearing cells expressed at the same time features of immature oligodendrocytes (O4 positivity) and of astrocytes [glial fibrillary acidic protein (GFAP) positivity]. A smaller proportion of them was labeled by the monoclonal antibody LB1. LB1+ or O4+ cells were rarely GFAP-, and GFAP+ cells were rarely LB1- or O4 . GalC+ oligodendrocytes were seen only occasionally, but the proportion of these cells increased up to 30% upon culturing in chemically defined medium containing 0.5% fetal calf serum. The L3 process-bearing cells accumulated the neurotransmitter gamma-aminobutyric acid (GABA), expressed the proteoglycan chondroitin sulfate, and responded to the mitogenic action of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). All these properties are characteristic of cells belonging to the O-2A (oligodendrocyte-type 2 astrocyte) cell lineage. The L3 flat cells were largely negative for the glial markers tested, but resembled type 1 astrocytes in their ability to support the growth of O-2A lineage cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254955 TI - Chemotaxis by a CNS macrophage, the microglia. AB - Microglia demonstrate many characteristics similar to those seen in monocytes and tissue-specific macrophages, including phagocytosis, production of oxygen radicals, and growth factors and expression of MHC antigens. We have examined the ability of microglia, cultured from the cerebral cortices of neonatal rats, to demonstrate another important functional characteristic of monocytic-derived cells, that is, chemotaxis. Our results show that cultured rat microglia demonstrate chemotaxis to complement dependent chemoattractants such as recombinant C5a, zymosan activated serum, and to rat serum as well as to transforming growth factor-beta, a chemoattractant produced by platelets. Microglia fail to migrate to bacterial dependent chemoattractants such as the N formyl peptides. The failure to respond is not dependent on maturational state of the microglia. Treatment with DMSO or casein, agents known to induce morphological and functional changes in cultured microglia reminescent of a "resting" and an "activated" macrophage, respectively, do not alter the response to fMet-Leu-Phe. In addition, the chemotactic response to serum in DMSO or casein treated cells is the same as the response seen in untreated day 10 cultured microglia or untreated age-matched controls. The ability of microglia to migrate in response to inflammatory mediators suggests that these cells can move to sites of injury, thereby enabling them to participate in an inflammatory response. PMID- 2254956 TI - Expression of glial fibrillary acidic protein and vimentin in mouse lens epithelial cells during development in vivo and during proliferation and differentiation in vitro: comparison with the developmental appearance of GFAP in the mouse central nervous system. AB - Analysis of glial fibrillary acidic protein (GFAP) and vimentin in mouse lens epithelial cells (MLEC) during ontogenesis revealed a two-step developmental expression similar to that observed in astrocytes. Vimentin was first immunostained at E11 corresponding with the closure of the lens vesicle, whereas GFAP was detected only after a further 7 days (E18); this protein appeared simultaneously in the mouse lens and CNS. In the latter case, it was present in the hypothalamic tanycytes and spinal cord. This similarity in the timing of appearance of GFAP in the non-neural MLEC and in fetal astrocytes suggests a common mechanism for its expression in tissues of different embryological origin. However, it has previously been observed that, in contrast to the situation in astrocytes, GFAP disappears from differentiating MLEC in vivo. We have shown that in vitro this protein also disappears rapidly from MLEC in the presence of fetal calf serum (FCS). However, the use of mouse serum instead of FCS inhibited the migration of MLEC out of the explant, and in these cells GFAP persisted. PMID- 2254957 TI - Lurcher Purkinje cells express glutamic acid decarboxylase and calbindin mRNAs. AB - Purkinje neurons in immature Lurcher (Lc/+) mice are destined to die as a result of a defect intrinsic to the dying cells. We have used in situ hybridization to determine whether the Lc allele interferes with the normal program of gene expression in the doomed Purkinje cells. In P21 mice, degeneration of Purkinje cells is well underway, but the surviving Purkinje cells continue to express the mRNAs for both glutamate decarboxylase and calbindin D28K, two proteins whose expression is characteristic of normal Purkinje neurons. We conclude that the Lc allele probably does not interfere with the developmental program but acts to cause cell death in already differentiated Purkinje neurons. PMID- 2254958 TI - Potassium-stimulated release of taurine from cultured cerebellar granule neurons is associated with cell swelling. AB - Effects of increased concentrations of potassium and of hyposmolar conditions on release of taurine were investigated in cerebellar granule neurons cultured from mice. It was found that increases in the external potassium concentration as well as decreases in osmolarity dose-dependently increased release of exogenously supplied [3H]-taurine and endogenous taurine from the neurons. The release of endogenous taurine elicited by a reduction of the osmolarity of the incubation media to 70% or 50% was much more pronounced than that of other amino acids, particularly glutamine, the release of which was not affected at all. The potassium-stimulated release of [3H]-taurine was strictly chloride dependent and it was inhibited by an increase of the osmolarity of the media as well as by 4,4' diisothyocyanostilbene-2,2'-disulfonate (DIDS) (100 microM). Moreover, a similar increase in the potassium concentration led to an increase in intracellular volume (swelling), a process which was also chloride dependent. It is concluded that potassium-stimulated taurine release from cerebellar granule neurons is associated with cell volume changes and that taurine is likely to play a role as an osmotically active substance in these neurons. PMID- 2254959 TI - Basic fibroblast growth factor in neuronal cultures of human fetal brain. AB - The presence of basic fibroblast growth factor (bFGF) was investigated in neuronal cells derived from 12 and 18 week-old human fetal brain cultures. To this purpose, the ability of bFGF to stimulate plasminogen activator (PA) production in fetal bovine aortic endothelial GM 7373 cells was used as an assay for this molecule in neuronal cell extracts. The identity of the PA-stimulating activity of neuronal cell extract with bFGF was confirmed by its high affinity for heparin and by its cross-reactivity with polyclonal antibodies to human placental bFGF. These antibodies recognized a Mr 18,000 cell-associated protein both in Western blot and in immuno-precipitation experiments. All the neurons showed bFGF immunoreactivity, as demonstrated by immunocytochemical staining, while nonneuronal cells were unstained. The data demonstrate for the first time that cultured human fetal brain neurons contain and synthesize bFGF. PMID- 2254960 TI - Development of cholinergic markers in the neuroblastoma, N1E-115. AB - The neuroblastoma, N1E-115, was grown for 9 days after subcultivation. The development of acetylcholinestrase (AChE), choline acetyltransferase (CAT), QNB binding, choline uptake, and acetylcholine release was measured on days 1, 3, 6, and 9. In parallel experiments the irreversible AChE inhibitor soman was added to neuroblastoma on day 1 and the development of the above parameters except for release, was followed. AChE activity in the normal cells was found to develop also after confluency, whereas CAT activity and QNB-binding followed the development of most of the cellular proteins, i.e., ceased to develop at confluency. Both choline uptake and acetylcholine release appeared independent of cellular development. In the soman-treated cells the development of AChE was inhibited for up to 6 days and thereafter developed with the same rate as in the normal cells. CAT and QNB-binding developed as in the normal cells, but at a significantly reduced level. The development of choline uptake was not significantly different in soman-treated and normal neuroblastoma. It is concluded that the development of the cholinergic marker QNB-binding is intimately associated with that of the "presynaptic" marker CAT, whereas the development of AChE seems to be unrelated to these cholinergic parameters. The choline transport and the acetylcholine release seem to be equally well expressed on all the days studied. PMID- 2254961 TI - Immunohistochemical localisation of nerve growth factor in a subpopulation of chick spinal ganglion neurons. AB - We have previously isolated and sequenced the chicken nerve growth factor (NGF) gene and now, from the deduced amino acid sequence, selected and produced peptides suitable for use as antigens. Anti-sera raised against these peptides inhibit the biological activity of a partially purified preparation of native chicken NGF and, when used in immunocytochemical studies, allow the visualisation of sensory neurons accumulating endogenous NGF. Immunoreactive cells form a distinct population of small neurons which may correspond to the well-described neurons generated in the dorsomedial area of spinal ganglia. We conclude that two subpopulations of neurons exist within dorsal root ganglia, whose requirements for, and use of, NGF may be quite distinct. PMID- 2254962 TI - Isolation, characterization, and substrate properties of the external limiting membrane from the avian embryonic optic tectum. AB - The external limiting membrane of the avian embryonic optic tectum is isolated by mechanically separating the neuronal mesencephalon from the overlying mesenchymal tissue. The preparation consists of a basal lamina which is covered on its neural side by endfeet of neuroepithelial cells and has attached to it on its meningeal side a collageneous stroma, containing blood vessels. The external limiting membrane can be flat-mounted on a piece of nitrocellulose filter as mechanical support. It covers an area between 0.3 and 1 cm2, depending on the age of the donor embryo. The endfeet can be removed together with all cellular components of the meninges by treatment with 2% Triton-X-100 or with distilled water. The basal lamina itself is approximately 80 nm thick and consists of two laminae rarae and a central lamina densa. Immunohistochemical staining reveals that the basal lamina in the embryo, after isolation and after detergent extraction of the isolated preparation, contains type IV collagen, nidogen, laminin, and low density heparan sulfate proteoglycan as do other basement membranes. Antibodies against the neural cell adhesion molecule (N-CAM), chondroitin sulfate proteoglycan, and fibronectin fail to stain the external limiting membrane, but these proteins were clearly identified in the blood vessel-containing meninges or in the optic tectum. The flat-mounted external limiting membrane preparation was used as substrate to culture several different neural tissues of central and peripheral origin. Explants of neural crest cells, dorsal root ganglia, and sympathetic ganglia can be cultured on the external limiting membrane. All explants grow well on the basal lamina preparations whether the endfeet are attached or detergent-extracted prior to explantation; however, neurite outgrowth from sympathetic ganglia is reduced in the presence of the endfeet. Although the endfoot-lined external limiting membrane represents at least part of the immediate environment encountered by retinal axons as they invade the optic tectum and despite its excellent properties as a substrate for retinal axons in vitro, cues guiding the orientation of axons were not detected in the flat mounted preparation. PMID- 2254963 TI - Phosphorylation of the glial fibrillary acidic protein. AB - The glial fibrillary acidic protein (GFAP) was found to be phosphorylated in vivo after intracerebral injection of [32P]-orthophosphate, in brain slices, and in a cell free system. The phosphorylated proteins were separated by two-dimensional gel electrophoresis and then transferred to nitrocellulose sheets. Two isoelectric variants of GFAP were immunochemically identified by monoclonal antibodies. Autoradiography demonstrated that only the more acidic isoelectric variant of GFAP was phosphorylated. Phosphoamino acid analysis revealed that under all conditions GFAP was phosphorylated at serine and threonine residues. Incubation of brain slices with [32P]-orthophosphate and the protein kinase C activator phorbol 12-myristate 13-acetate or forskolin, an activator of cyclic AMP-dependent protein kinase, stimulated phosphorylation of GFAP. Likewise phosphorylation of GFAP was also accentuated by calcium/phosphatidylserine/diolein and by exogenous cyclic AMP-dependent kinase in a cell free system. These findings announce that protein kinase C and cyclic AMP dependent kinase may play physiologic roles in the in situ phosphorylation of GFAP. When isolated cytoskeletal preparations were incubated with [gamma-32P] ATP, GFAP was phosphorylated in vitro by two additional protein kinases, a Ca2++/calmodulin-dependent kinase and an effector-independent kinase. The results of these investigations strongly suggest that phosphorylation of GFAP appears to be regulated by multiple second messenger pathways. PMID- 2254964 TI - Prolonged ongoing discharges of sensory nerves as recorded in isolated nerves in the rat. AB - Whether or not injury to a mammalian sensory nerve produces prolonged discharges is a controversial issue. Because of this controversy and its potential ramifications in both experimental and clinical conditions, we examined discharges in sectioned sensory nerves of the rat. In anesthetized rats, either a dorsal root or a saphenous nerve was isolated by sectioning both proximally and distally. Multi-unit recordings from these isolated nerves showed low levels of prolonged ongoing discharges often lasting for at least 2 hr. Furthermore, results from short-term (1-2 days) survival surgeries indicated that prolonged ongoing discharges could last for days. Sectioning the ventral root produced discharges for only a short period. Various pieces of evidence suggested that the sources of impulse generation are multiple, occurring in the middle of an uninjured axon at a site away from the injury, as well as at the injured site. There is circumstantial evidence which suggests that these prolonged discharges are produced in physiological conditions or at least under normal experimental conditions. PMID- 2254965 TI - Effects of in utero ethanol exposure on the developing dopaminergic system in rats. AB - Previous studies from this and other laboratories suggest that dopamine is decreased in selected brain regions of postnatal rats exposed to ethanol in utero. The present study expands previous work by examining the effects of in utero ethanol exposure on dopamine D1 and D2 binding sites and dopamine uptake in postnatal rats. In addition, dopamine content in the brain stem and frontal cortex of fetal and neonatal rats was examined. The experimental results indicate that in utero ethanol exposure markedly affects the postnatal development of the dopaminergic system in the striatum and frontal cortex. We observed a marked, transient deficiency of striatal dopamine (greater than 40% decrease at 19 days) and dopamine uptake sites (approximately 25% decrease in Vmax at 35 days). The Bmax for striatal dopamine D1 binding sites was decreased by greater than 20% at both 19 and 35 days. Cortical D1 sites were markedly decreased at 19 days (greater than 40%). In contrast, the number of striatal D2 receptors was unaffected by in utero ethanol exposure at both ages. Analysis of tissue from neonatal rats demonstrated a marked dopamine deficiency in ethanol-exposed rats on postnatal day 5. In light of the proposed morphogenic actions of dopamine early in development, it is possible that the early dopamine deficiency contributes to the abnormal postnatal development of the dopaminergic system. PMID- 2254966 TI - Amino acid content of rat cerebral astrocytes adapted to hyperosmotic medium in vitro. AB - Rat cerebral astrocytes from confluent primary cultures were grown for two weeks in medium made hyperosmotic with additional NaCl. At the time the cells were harvested (four weeks in culture), the medium osmolality of experimental cultures was approximately 600 mOsm. Amino acid, protein, and potassium contents and the cell volume were measured. Compared to cells maintained in control medium (approximately 300 mOsm), cells grown in hyperosmotic conditions had over two times the content of taurine and five times the content of glutamine. Alanine, aspartate, glutamate, glycine, and tyrosine contents also were elevated in these hyperosmotic-treated cells, while asparagine contents were unchanged relative to control cells. Cell volume and potassium content were decreased to approximately 50% of control levels by the hyperosmotic treatment while total protein content per cell was unchanged relative to cells from control cultures. Seven min after hyperosmotic-exposed cells were rapidly diluted into PBS with osmolality equal to about 330 mOsm, cell contents of alanine, asparagine, glutamine, glutamate, glycine, taurine, and tyrosine fell toward control levels. The data indicate that significant alterations in intracellular osmolytes occur in astrocytes adapted to hyperosmotic conditions. We suggest that a loss of intracellular potassium is at least partially compensated by accumulation of taurine, glutamine, and perhaps other amino acids acting as intracellular osmolytes. PMID- 2254967 TI - Nutrition and metabolism. PMID- 2254968 TI - Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis. AB - Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality. Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible. The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established. This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis. PMID- 2254969 TI - Evolution of trauma and trauma research. PMID- 2254970 TI - Topical wound therapy--an historical perspective. PMID- 2254971 TI - Basic principles of wound healing. PMID- 2254972 TI - Current concepts in wound healing: growth factor and macrophage interaction. AB - Growth factors are potent wound healing promoters which accelerate incisional wound repair by distinct mechanisms. Transforming growth factor-beta (TGF-beta), a chemotactic factor, increases synthesis of extracellular matrix and stimulates granulation tissue. We demonstrated that a single topical dose of TGF-beta increased the wound breaking strength in normal models of tissue repair as well as in models of impaired wound repair, characterized by severe monocytopenia. PDGF, a chemotactic agent for inflammatory cells, with mitogenic activity, activates monocytes and stimulates collagen production, significantly increased the wound breaking strength with effects that lasted for up to 47 days. In contrast to TGF-beta, PDGF was only active in normal models of wound healing and its effects were dependent upon the presence of macrophages. PAF is a glycerophospholipid which chemotaxes and activates macrophages, but differs from growth factors in lacking mitogenic activity. A single topical dose of PAF significantly increased the wound breaking strength and promoted macrophage migration. PMID- 2254973 TI - The activated keratinocyte: up regulation of cell adhesion and migration during wound healing. AB - Keratinocytes play different roles in normal and wounded skin. In normal skin, these cells are specialized for differentiation. In wounded skin, they are specialized for migration. This article discusses the idea that migratory competent keratinocytes are "activated." Changes that characterize the activation process include increased cell attachment, spreading, focal adhesion formation, and migration. In part, these changes can be explained by enhanced expression of alpha 5 integrin subunits and reorganization of beta 1 integrin subunits. PMID- 2254974 TI - Models of wound healing. AB - The investigation of wound healing is dependent on the use of various models. This paper reviews several methods used to study wound healing, particularly in regard to connective tissue metabolism. The usefulness and potential pitfalls of cell culture are discussed. Several species of animals have been used as models for human healing, rodents being the most frequently employed. In an attempt to provide better wound tissue sampling from these animals, insertable devices have been developed that allow the ingrowth of healing tissue. Several of these devices are reviewed with reference to their advantages and disadvantages. Connective tissue deposition into wounds can be evaluated by wound strength measurement and hydroxyproline quantitation. Histologic methods are available to evaluate the cellular and matrix details within the wound. Additionally, methods developed in molecular biology are becoming applicable to healing studies and a safe means of investigating collagen metabolism in humans by the use of a stable oxygen isotope is being developed. The study of fetal wound healing provides an excellent example of the utility of many of these methods in achieving an understanding of the biology of this remarkable scarless process. PMID- 2254975 TI - Current status of skin replacements for coverage of extensive burn wounds. PMID- 2254976 TI - Multiple organ failure: clinical overview of the syndrome. PMID- 2254977 TI - Etiology of multiple organ failure. PMID- 2254978 TI - The systemic septic response: concepts of pathogenesis. AB - Following resuscitation from shock, the clinical phase of persistent hypermetabolism is entered from which a substantial number of patients transcend into progressive organ failure and expire. The available epidemiologic, physiologic, and metabolic data are consistent with the position that a persistent degree of microcirculatory hypoxia, although it may be present in amounts that are below the sensitivity of current detection systems, becomes an increasingly less important etiologic factor as the organ failure disease progresses. Rather, aerobic metabolism appears to be the dominant mechanism of meeting the increased work loads and energy demands. There is an increasing body of evidence that cytokine release systemically, and increased cell-cell interaction through cytokines and prostanoids locally, may alter not only parenchymal function in the proximity of these mononuclear cells, but organ function at distant sites. If this latter hypothesis continues to be substantiated, it implies that the underlying cell and organ dysfunction may indeed be reversible if appropriate counter-regulatory mechanisms could be developed and the appropriate timing of their application understood. PMID- 2254979 TI - Biliary and gut function following shock. AB - The aim of this study was to characterize the alterations in gallbladder and intestinal function after hemorrhagic shock and blood reperfusion in opossums. Animals were subjected to a shock of 30 mm Hg of arterial blood pressure for 60 minutes and resuscitated with blood reinfusion. Gallbladder epithelial ion transport, gallbladder motility in vitro and in vivo, gastrointestinal motility, and flora of the stomach and small bowel were studied 2 and 24 hours after shock. Changes at 2 hours included decreased gallbladder contractility in vitro and decreased emptying in vivo, loss of coordination with intestinal motor activity, decrease in frequency of intestinal electrical slow waves, and reduced duration of the intestinal migrating motor complex cycle. By 24 hours, gallbladder epithelial permeability was increased and in vitro contractility remained reduced but the in vivo functions showed partial recovery. Gastrointestinal flora was not affected by these changes. These data demonstrate that hemorrhagic shock and reperfusion affect digestive motility. The early timing of the alterations observed and the partial recovery 24 hours post shock suggest an ischemia-hypoxia mechanism of injury. PMID- 2254980 TI - Bacterial translocation of the gut flora. PMID- 2254981 TI - A new model of macrophage stimulation by bacterial lipopolysaccharide. AB - Infection occurring in patients suffering from severe trauma or burns often leads to hypotension, disseminated intravascular coagulation, multiorgan failure, and death. These latter pathophysiologic changes often are associated with Gram negative sepsis and endotoxemia. Substantial progress has been made in understanding the effector mechanisms for endotoxin (LPS) action with the recognition of the importance of LPS-inducible products of cells of monocytic lineage in mediating LPS-induced injury. Here we will review recent evidence that supports a model for monocyte/macrophage activation by LPS that involves a plasma protein known as lipopolysaccharide binding protein (LBP) and the monocyte differentiation antigen, CD14. PMID- 2254982 TI - Altered Ca2+ homeostasis and functional correlates in hepatocytes and adipocytes in endotoxemia and sepsis. AB - Decreased cytosolic [Ca2+] and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis. These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by [Ca2+]c and defective phosphorylation of relevant enzymes. Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae. ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic [Ca2+] under basal conditions and upon ACTH stimulation than that observed in cells of control rats. The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats. Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation. PMID- 2254983 TI - Summary of staging mechanism and intervention studies in the baboon model of E. coli sepsis. PMID- 2254984 TI - Assessing nutritional needs for the burned patient. AB - Assessment of nutritional needs following thermal injury remains an important adjunct to providing dietary therapy designed to minimize the detrimental effects of hypermetabolism and subsequent catabolism. Most anthropometric measurements, frequently utilized in nonburned patients, have relatively little usefulness in assessing burned individuals. Energy expenditure can be adequately estimated for most patients by direct calorimetry, indirect calorimetry, or formulae. Direct calorimetry is the most expensive and complicated method, while use of a formula is the most inexpensive and least complicated. All yield good results in the clinical setting. Differences in estimated energy expenditure by the multiple formulae may be statistically significant, but rarely are clinically significant. Therefore selection of a formula should be based on simplicity. Estimations by formula require readjustment at intervals of 1 to 2 weeks. In general, enteral feedings remain superior to parenteral delivery of nutrients. Finally, current animal research suggests significant differences in metabolic and immunologic effects of the diet depending on qualitative make-up of dietary fat sources. PMID- 2254985 TI - Future prospectives in trauma and burn care. PMID- 2254986 TI - Effect of early feeding on the postburn hypermetabolic response in rats. AB - The effect of early enteral feeding on the hypermetabolic response following burn injury in a rat burn model has been investigated. The rates of heat production and partitioned heat loss were determined on the fourteenth postburn day for five treatment groups: I) burn, fed rat chow ad libitum starting 2 hours postburn; II) burn, fed by gastrostomy beginning 2 hours postburn; III) burn, fed by gastrostomy, delayed until 72 hours postburn; IV) controls, fed by gastrostomy 2 hours post anesthesia; and V) controls, fed rat chow ad libitum 2 hours post anesthesia. Gastrostomy feedings delivered 175 kcal/kg.day. The mean rates of heat production and heat loss for the three burn groups did not differ significantly whether rats were fed chow ad libitum, or by gastrostomy early or late. Contrary to previous studies using a guinea pig model, method and timing of feeding in this burned rat model had no significant effect on the postburn increment in the rate of heat loss and the corresponding increment in the rate of heat production. PMID- 2254987 TI - Antibiotics and the postburn hypermetabolic response. AB - Severe burn injury has been documented to significantly increase resting metabolic energy expenditure. This increase in metabolic rate appears to be possibly correlated with the degree of burn wound colonization and infection with bacteria. Prevention of such colonization and infection through the use of topical antimicrobial agents appears to decrease the metabolic alterations resulting from burn injury. These findings indicate that appropriate use of topical antibacterial agents may decrease the metabolic demands seen in burned patients. Burn-induced translocation of intestinal bacteria has also been hypothesized to contribute to the postburn hypermetabolic response. Attempts at preventing this entity in a burned guinea pig model through the use of selective decontamination of the digestive tract by the administration of enteral antibiotics have failed to demonstrate any measurable effect. PMID- 2254988 TI - From desperation to skin regeneration: progress in burn treatment. PMID- 2254989 TI - Pathophysiology of the hypermetabolic response to burn injury. PMID- 2254990 TI - Pulmonary circulation and burns and trauma. AB - The lung is a critical organ in victims of thermal injury or multiple trauma since the blood that drains injured organs circulates through the pulmonary circulation before passing through any other organ. The lung therefore will receive the first volley of cytotoxins released postinjury. In addition to being a target of injury, the lung may also contribute to the injury of systemic organs. This injury may be the result of a reduced delivery of oxygenated blood or the direct release of cytotoxins into the systemic circulation. The injury to the lung may be to the pulmonary microvasculature or the airway. The bronchial circulation responds to injury by a marked elevation in its blood flow and microvascular permeability. These latter effects may be important in mediating the changes which occur in the lung parenchyma. PMID- 2254991 TI - Endotoxin requirements for alveolar macrophage stimulation. AB - Acute pulmonary failure or ARDS in severely injured patients continues to be a significant problem. The most important clinical risk factor identified is sepsis syndrome. Sepsis syndrome is the clinical correlate of a malignant systemic inflammatory process and is directed in large part by the tissue-fixed macrophage (M phi), such as the alveolar M phi. The M phi is capable of producing most of the central inflammatory mediators responsible for the pathophysiology seen during sepsis and organ injury. Two major mediators are procoagulant activity (PCA), leading to diffuse microvascular thrombosis, and tumor necrosis factor (TNF), causing much of the physiologic derangement of sepsis. Endotoxins (LPS) derived from Gram-negative bacterial cell walls are the primary inflammatory stimulus for the tissue-fixed M phi production of inflammatory mediators. It is not completely known how LPS interacts with its various cellular targets, but it is hoped that knowledge of the molecular interactions involved in stimulation of the M phi by endotoxin will lead to therapies to modulate the response and prevent deleterious processes such as ARDS. In the present studies, LPS from E. coli 0111:B4 was shown in a dose response to stimulate large levels of both PCA and TNF in alveolar M phi. LPS from Bacteroides fragilis and Lipid X (the monosaccharide precursor of endotoxin) were unable to cause stimulation of the M phi in vitro. However, both moieties, B. fragilis LPS and Lipid X, were able to effectively and specifically compete with E. coli LPS and block M phi stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2254992 TI - Identification and modifications of the pulmonary and systemic inflammatory and biochemical changes caused by a skin burn. PMID- 2254993 TI - Substrate cycling in thermogenesis and amplification of net substrate flux in human volunteers and burned patients. PMID- 2254994 TI - Evaluation and management of patients with inhalation injury. AB - Inhalation injury, present in approximately one third of burned patients treated at burn centers, increases mortality by a maximum of 20% in relation to age and extent of burn. The development of animal models of inhalation injury has made possible the identification of both the airway and vascular responses evoked by smoke inhalation. Inflammatory occlusion of terminal bronchioles and necrosis of the endobronchial mucosa render the airway and pulmonary parenchyma susceptible to infection and the resulting pneumonitis further increases mortality. Early diagnosis, best achieved by endoscopic bronchoscopy and 133xeon ventilation perfusion scan, permits timely application of high-frequency ventilation that appears to reduce the incidence of pneumonia and to decrease mortality. Pharmacologic agents give promise of ameliorating the deleterious changes of the vasculature. The recent advances in understanding inhalation injury have identified the research needed to further improve patient salvage. PMID- 2254995 TI - Mechanism of immunologic suppression in burn injury. PMID- 2254996 TI - Pathophysiologic events related to thermal injury of skin. AB - Acute thermal injury of skin equivalent to second-degree injury and involving approximately 25% of total body surface results in a series of pathophysiologic events which lead to both local and distant tissue/organ injury. The distant effects involve intravascular hemolysis and acute lung injury, both of which can be attributed to complement activation and intravascular stimulation of neutrophils, resulting in oxygen radical production, which results in injury of red cells and pulmonary vascular endothelial cells. At the local site of thermal injury, the progressive increase in vascular permeability is linked to complement activation and histamine release, the outcome of which is interaction of histamine with xanthine oxidase, resulting in enhanced catalytic activity of the enzyme. Toxic oxygen products of xanthine oxidase, including H2O2 and its conversion product, the hydroxyl radical, appear to be linked to the damage of dermal vascular endothelial cells, resulting in progressive vascular permeability. The increased vascular permeability can be greatly attenuated by the use of inhibitors of xanthine oxidase, the inhibitor of histamine release (cromolyn), catalase, an iron chelator (deferoxamine), or scavengers of the hydroxyl radical. Interestingly, neutrophils appear to play little if any role in dermal vascular injury in this animal model of thermal trauma. Those studies suggest that pathophysiologic events following local thermal trauma are complex and involve a variety of mediator pathways. PMID- 2254997 TI - Neutrophil disorders in burn injury: complement, cytokines, and organ injury. AB - Because of the association of burn injury with subsequent bacterial infection, numerous studies have been performed characterizing neutrophil function in burn injury. These studies provide a picture of intravascular complement activation, neutrophil-C5a interactions, and consequent disordered cellular function. Neutrophil dysfunction includes suppressed random and C5a-directed migration and hyperresponsiveness to oxidative stimuli. These observations do not explain the histologic and functional involvement of neutrophils in ARDS and perhaps other organ failure states. Circumstantial and extrapolated information suggests that macrophage-lineage cells function as regulators of neutrophil function within matrix environments in burn injury. Elevated endotoxin levels have been found in burned patients, which would support the notion of endotoxin-stimulated monocytes/macrophages as inducing neutrophil migration into connective tissue matrices (LTB4 and IL-8), inducing prolonged oxidant production (TNF-alpha, GM CSF), and inducing neutrophil release of regulatory substances from neutrophils (G-CSF). This information suggests a variety of experimental approaches to testing this hypothesis. PMID- 2254999 TI - The regulatory role of T lymphocytes in wound healing. PMID- 2254998 TI - Aberrations in post-trauma monocyte (MO) subpopulation: role in septic shock syndrome. AB - Appearance of increased proportions of monocytes bearing the 72kd(FcRI) receptor for IgG correlated to aberrant monocyte (MO) functions, depressed immune functions, and poor clinical outcome. The trauma patients' FcRI+ MO subpopulation produced the majority of their elevated IL-6, TNF alpha, TGF beta, and PGE2. IgG stimulation of patients' MO through FcRI not only stimulated TNF alpha, IL-6, and PGE2 levels, but also greatly augmented the levels of these monokines produced after subsequent bacterial challenge. Post-trauma increased IL-6 levels can lead to polyclonal B-cell activation and high levels of circulating, nonspecific IgG as seen in trauma patients. This nonspecific IgG triggers the FcRI on the increased numbers of FcRI+ MO leading to ever-increasing monokine levels. IL-4 was found to downregulate patients' FcRI+ MO production of mediators. The cycle of altered cytokine levels, increased FcRI+ MO numbers, elevated IgG, and augmented triggering of FcRI+ MO may be broken by addition of IL-4. PMID- 2255000 TI - Effect of immunosuppressive factor produced by human lung cancer cell line A549 on the production and action of interleukin 1. AB - A549, a human lung cancer cell line, spontaneously produces a tumor-derived immunosuppressive factor (TDSF) which inhibits the production and action of interleukin 1 (IL-1). After exposure of macrophages to TDSF for 5 h, the production of IL-1 by macrophages was significantly inhibited. The inhibition was much stronger if TDSF existed continuously in macrophage culture. The response of thymocytes treated with nylon wool to exogenous IL-1 was significantly suppressed in the presence of TDSF, suggesting that TDSF can inhibit the action of IL-1. The thymocytes untreated with nylon wool could proliferate after being stimulated with Con A. The proliferation was significantly suppressed by TDSF in a dose dependent manner. These results suggest that the inhibitory action of TDSF on T cell activation is associated with IL-1, and that TDSF might exert an inhibitory action on other reactions mediated by IL-1. Furthermore, TDSF can reduce the supplementation of new T cells by inhibiting the proliferation of thymocytes. PMID- 2255002 TI - Influence of ginseng upon the development of liver cancer induced by diethylnitrosamine in rats. AB - The influence of ginseng upon the development of liver cancer induced by diethylnitrosamine (DEN) in rats was observed with histochemical methods and microscopy. The incidence of liver cancer was 14.3% in the experimental group and 100% in the control group, with the difference being statistically significant. Degeneration and necrosis of the hepatocytes in the experimental group were milder than in the control group. Histochemical studies also revealed that the activity of SDH, 5'-NT and gamma-GT, and the amounts of DNA, RNA and glycogen in the experimental group were maintained at relatively normal level, and decreased or increased in the control group. The results obtained in our experimental studies indicated that the ginseng seems to play a role of protecting the hepatocyte from injury by DEN, thereby inhibiting the development of liver cancer induced by DEN. PMID- 2255001 TI - Strain difference in pulmonary vascular responsiveness to hypoxia in rats. AB - The difference in pulmonary vascular response to hypoxia between Hilltop Sprague Dawley (HT) rats and Wistar (W) rats was studied. Effects of inhibitor of leukotriene (LT) synthesis or prostaglandin (PG) synthesis on hypoxic pulmonary vasoconstriction (HPV) and chronic pulmonary hypertension were observed, and variations in plasma TXB2 and 6-keto-PGF1 alpha during hypoxia were determined. The results showed that in rats of both strains LTs are the major mediator of HPV, which is also mediated by vasoconstrictive PGs in HT rats, while modulated by vasodilative PGs in W rats. This might be the crucial mechanism responsible for the higher pulmonary vascular responsiveness in HT rats. Differences in the modulating effect of histamine and in the structural feature of pulmonary arteriole might be contributing factors as well. PMID- 2255003 TI - Studies on hemorrheology in dogs with cirrhotic portal hypertension. AB - Eight dogs with cirrhotic portal hypertension were investigated for hemorrheology and hepatic hemodynamics. The whole-blood viscosity decreased in dogs with liver cirrhosis. The decrease in hematocrit may be responsible for low blood viscosity in cirrhosis. It was also found that the increase in portal venous resistance in cirrhosis was related to the anatomical changes of portal venous bed, but not to blood viscosity. Moreover, our experimental results indicated that raising blood viscosity might be one of the important measures for the treatment of esophageal variceal hemorrhage and for the prevention of rebleeding. PMID- 2255004 TI - Comparison of pre-S1 and pre-S2 proteins in hepatocytes with replication by in situ hybridization assay. AB - To compare the relationship of pre-S1 and pre-S2 proteins in hepatocytes with HBV replication, HBVDNA in situ hybridization was performed for a group of patients with chronic hepatitis by bio-probe, in conjunction with detection of intrahepatic HBsAg, HBcAg, pre-S1 and-S2 antigens. It was found that the expression of intrahepatic pre-s1 and pre-S2 proteins was visualized as cytoplasmic homogeneous and inclusion types, on some occasions as membranous localization. However, the positive rate for pre-S1 protein was up to 75% (15/20), being significantly higher than that of pre-S2 protein (35%; 7/20) in the same group (P less than 0.05). What in more important, the pre-S1 expression, rather than pre-s2, was in parallel with the presence of intrahepatic HBVDNA and HbcAg. All these findings suggest that the pre-S1 protein might be mainly expressed at the HBV replication phase, thus, to some extent, the detection of pre-S1 protein might complement HBe system and HBVDNA clinical routine. PMID- 2255005 TI - Effects of nifedipine on diastolic function in hypertensive patients--an echocardiographic study. AB - This study was undertaken to observe the changes in heart function and evaluate the effects of nifedipine on diastolic function in 70 patients with uncomplicated hypertension by M-mode and Doppler echocardiography. The results showed that diastolic abnormalities in hypertensive patients may precede systolic dysfunction and that nifedipine can improve diastolic function. It is easy and quick to estimate the diastolic function by measuring the EF slope, EA and EPSS, especially the E wave velocities. This method proved to be applicable to clinical practice. PMID- 2255006 TI - Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against leukemia and myeloma: II. Preparation and characteristics of monoclonal anti isotypic antibodies to IgM from B chronic lymphocytic leukemia. AB - Five hybridomas producing McAbs against human serum IgM-isotype were obtained by fusing the myeloma NS-1 cell and the BALB/C murine spleen cell which had been immunized by serum IgM of patient with B chronic lymphocytic leukemia (B-CLL). These McAbs only reacted with human IgM, not with other immunoglobulins in ELISA and immune double diffusion test. An approximate positive rate of peripheral blood lymphocyte (PBL) was got when these McAbs and the McAbs against B cell were tested by indirect immunofluorescent assay. The positive rate was similar to that obtained by direct immunofluorescent test. Immunoblotting showed that the molecular weight of the antigen to these McAbs was 70-90 Kd, indicating that the antigen was IgM. The practical value of the McAbs against human IgM was also discussed. PMID- 2255008 TI - Heart research efforts aim at fairness to women in terms of causes, care of cardiac disorders. PMID- 2255007 TI - Flow cytometry DNA measurement for prediction of effect of therapy in acute leukemia. AB - We measured the DNA content of bone marrow (BM) aspirate by flow cytometry (FCM) in 41 cases of acute leukemia (AL) and found no remarkable relation between pretreatment DNA index and percentage of proliferative cells and prognosis (P greater than 0.05). After chemotherapy, reduction of proliferative cells rate, disappearance of DNA aneuploidy and decrease of leukemic cells in BM could be considered as the reliable indicators of effective treatment. Complete remission (CR) rate was significantly higher in patients responsive to treatment (81.82%) than in those unresponsive (22.22%; P less than 0.05). It seems that these parameters may serve as indicators of efficiency of chemotherapy and be useful in monitoring regimen in time and in reducing the occurrance of chemotherapy resistance, thereby facilitating individualization of chemotherapy in AL patients. PMID- 2255010 TI - Managing hypertension in pregnancy. PMID- 2255009 TI - Gene scene: earlier, eventually more specific, prenatal genetic diagnosis in realm of possibility. PMID- 2255011 TI - From the Centers for Disease Control. Regional variation in diabetes mellitus prevalence--United States, 1988 and 1989. PMID- 2255012 TI - From the Centers for Disease Control. Prevalence, incidence of diabetes mellitus- United States, 1980-1987. PMID- 2255013 TI - Physicians and human rights. PMID- 2255014 TI - Peer review. PMID- 2255015 TI - Peer review of papers for presentation at meetings. PMID- 2255016 TI - Peer review and dissenting manuscripts: the Cantekin case. PMID- 2255017 TI - The consequences of a fraudulent scientist on his innocent coinvestigators. PMID- 2255018 TI - Cardiac surgery in La Jolla: an error perpetuated. PMID- 2255019 TI - Glaucoma and impotence. PMID- 2255020 TI - Regional variation in hip fracture: is it due to increased milk consumption in the North, 50 years ago? PMID- 2255021 TI - A surgeon with AIDS. PMID- 2255022 TI - Treatment failure after substitution of generic pancrelipase capsules. PMID- 2255023 TI - Adolescent suicide attempters. Response to suicide-prevention programs. AB - As part of a controlled evaluation of three suicide-prevention curricula delivered to 1438 ninth- and 10th-grade students, 63 adolescents were identified as having made a suicide attempt. Their attitudes about suicide and help seeking were compared with those of 910 nonattempters drawn from the same population. Reaction to the prevention program was assessed by comparing the responses of the 35 attempters exposed to the programs with responses of 524 exposed nonattempters. The impact of the programs was assessed by comparing 35 exposed attempters with 28 attempters from a control group. Self-identified attempters were less likely to endorse views consistent with the curricula at baseline, but there was little evidence that the programs were successful in influencing these views. There was some evidence that previous attempters were more upset by the programs than their nonattempter peers. The prevalence of suicide attempts as defined in this study by self-report was higher than that reported in studies using interview techniques. PMID- 2255024 TI - Derivation and validation of a clinical diagnostic model for chlamydial cervical infection in university women. AB - We developed and prospectively tested a logistic regression model for chlamydial cervical infection. Study subjects included 2271 women receiving gynecologic care in our student health clinic. Clinical data were collected in a standardized fashion. We identified cell culture--isolated Chlamydia trachomatis from 133 (9%) of 1458 subjects in the derivation set and 73 (10%) of 729 subjects in the validation set. Model variables included a new sexual partner within 2 months or more than one sexual partner within 6 months; cervical ectopy; cervical friability; at least 20 polymorphonuclear leukocytes per high-power field in cervical secretions; white blood cells in vaginal secretions; and use of an antibiotic active against C trachomatis within a month. This model can distinguish women with low, medium, and high risks of chlamydial infection (on derivation set: receiver operating characteristic curve area, 0.710; SE, 0.026; on validation set: area, 0.698; SE, 0.035) using simple clinical information obtained in the office. PMID- 2255025 TI - Environmental illness. A controlled study of 26 subjects with '20th century disease'. AB - Environmental illness is a polysymptomatic disorder believed by "clinical ecologists" to result from immune dysregulation brought on by common foods and chemicals. We systematically evaluated 26 subjects who had been assigned a diagnosis of environmental illness. The subjects indicated a strong interest in their diagnosis, were generally satisfied with their clinical ecologist, and were dissatisfied with traditional medical approaches. Subjects reported varying treatments, including dietary restrictions, avoidance of offending agents, and physical treatments. Using the Diagnostic Interview Schedule, we found that 15 (65%) of 23 subjects met criteria for a current or past mood, anxiety, or somatoform disorder compared with 13 (28%) of 46 age- and sex-matched community controls. We conclude that patients receiving this diagnosis may have one or more commonly recognized psychiatric disorders that could explain some or all of their symptoms. PMID- 2255026 TI - Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled, double-blind, randomized trial. AB - One hundred fifty-five consecutive patients resuscitated after out-of-hospital ventricular fibrillation by a physician-manned advanced life support unit were randomly assigned to receive nimodipine or placebo at a dosage of 10 micrograms/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 micrograms/kg per minute for 24 hours. No significant difference was found in the 1-year survival rate of nimodipine-treated (30 [40%] of 75 patients) and placebo-treated patients (29 [36%] of 80 patients). Recurrent ventricular fibrillation during the treatment occurred in one patient in the nimodipine group compared with 12 patients in the placebo group. In a post hoc analysis of patients with very long delays in advanced life support (more than 10 minutes), the 1-year survival rate was higher with nimodipine (eight [47%] of 17 patients) than with placebo (two [8%] of 26 patients). Nimodipine may be of benefit in patients with delayed resuscitation. PMID- 2255027 TI - Surgical professor for three eventful decades. PMID- 2255028 TI - NIH consensus conference. Intravenous immunoglobulin. Prevention and treatment of disease. PMID- 2255029 TI - Youth suicide: the physician's role in suicide prevention. PMID- 2255030 TI - Ex-hostage unsure of Hussein, but knows, 'hurrah for freedom!'. PMID- 2255031 TI - Diagnostic and therapeutic technology assessment. Allogeneic bone marrow transplantation for chronic myelogenous leukemia. PMID- 2255032 TI - [The anesthesiologist and emergency medicine]. PMID- 2255033 TI - [Effects of negative extra-thoracic pressure ventilation on respiratory system and hemodynamics in normal dogs]. AB - The effects of negative extra-thoracic pressure ventilation (NETPV) on respiratory system and hemodynamics were examined in ten normal dogs. Changes of the parameters obtained during intermittent NETPV (INETPV), and NETPV with negative end-expiratory pressure (CNETPV) were compared with those during IPPV and CPPV. Animals' chests and upper abdomens were confined in an acryl box. In INETPV and CNETPV, the dogs were ventilated with the negative extra-thoracic pressure ventilator (Kimura, OKT-100). Positive and negative pressure ventilation was carefully matched for tidal volume and the increase in FRC obtained with PEEP and the end-expiratory negative extra-thoracic pressure (EENETP). EENETP of -11.6 cmH2O produced the same FRC change as PEEP of 10.6 cmH2O did. Gas exchanges did not differ in any modes. INETPV did not change any hemodynamic parameters without PAP. In CNETPV, heart rate increased, and CVP, cardiac index (CI) and stroke volume (SV) decreased significantly (P less than 0.05), but tmCVP and tmPCWP did not change. The decreases of CI and SV (100----89.1, 88.8%) in CNETPV were significantly smaller when compared with CPPV (100----78.8, 74.5%). In CPPV, meanBP, CVP, tmCVP, tmPCWP, CI, SV changed significantly. The mechanisms of the decrease of CI and SV by CNETPV seemed to be different from those by CPPV. PMID- 2255034 TI - [Respiratory distress after endotracheal insufflation of baby powder in dogs]. AB - The cause of delayed respiratory distress after endotracheal insufflation of baby powder was investigated in dogs. Ten dogs were divided into 2 groups. In the insufflation group (n = 6), baby powder 1g.kg-1 was insufflated through an endotracheal tube under controlled mechanical ventilation. In the control group (n = 4), artificial ventilation was continued for 36 hours without insufflation of baby powder. PaO2 in the insufflation group fell until 1 hour, and then improved until 12 hours after the insufflation. But PaO2 fell again after 12 hours, and all dogs died by 36 hours after the insufflation. Pathological examination of the lungs of the insufflation group revealed gram-negative bacillus pneumonia, but no pneumonia occurred in the control group. Gram-negative bacillus was not detected in the baby powder, but Acinetobacter calcoaceticus was found from the tracheal swabs of the dog. Therefore, delayed respiratory distress was thought to have been caused by A. calcoaceticus pneumonia. It was concluded that A. calcoaceticus, which comprises a part of the indigenous flora of the respiratory tract of the dog, finally caused pneumonia and death of the dogs after baby powder insufflation because baby powder had damaged the lung's defence of bacterial clearance. PMID- 2255035 TI - [Evaluation of noninvasive monitoring of preoxygenation]. AB - Administration of 100% oxygen before a "rapid-sequence" induction of anesthesia is recommended to prevent hypoxemia during induction. In the present study, we used a laser scattering analyzer to study the effectiveness of nitrogen washout from the lungs with oxygen wash into the lungs under two different preoxygenation regimens; 4 times of maximal breathing of 100% oxygen in one minute and normal tidal breathing of 100% oxygen for 3 minutes. The volunteers were healthy, ASA physical status 1, 22 to 33 years of age (26 +/- 3), 167 +/- 5 cm tall, and weighing 60 +/- 5 kg. Arterial blood saturation measured by a pulse oximeter was 97 while breathing 21% oxygen, and 99% while breathing 100% oxygen. Arterial oxygen tensions were 98 mmHg while breathing 21% oxygen, and over 480 mmHg while breathing 100% oxygen. Arterial carbon dioxide and end tidal carbon dioxide concentrations indicated that 4 time of maximal breathing in a minute leads to hyperventilation. The end-tidal oxygen concentration was not significantly different between before and after oxygen administration in two different regimens. End-tidal nitrogen concentration after tidal volume ventilation was lower than that of 4 breath in a minute. These results indicate that end-tidal nitrogen and oxygen could reflect arterial nitrogen and oxygen tensions during preoxygenation. PMID- 2255036 TI - [Changes in systemic circulation and organ blood flow during induced total spinal block]. AB - Total spinal block with lidocaine was performed in adult mongrel dogs, and circulatory changes or changes in organ blood flow were investigated. Dogs were divided into group A (5.1 mg.kg-1) and group B (10.0 mg.kg-1) according to the dose of lidocaine. During total spinal block, HR (79% and 78%), MAP (64% and 69%), LV dp/dt max (58% and 49%) and CI (67% and 67%) decreased significantly compared with the control values in groups A and B respectively. However, SVR was unchanged. The circulatory change occurred more rapidly in group B. Organ blood flow was measured in group A. Blood flow was measured in four areas during total spinal block. It was significantly decreased at liver and slightly decreased at cerebral cortex and medullary substance. However, renal cortex blood flow was not altered. PMID- 2255037 TI - [Effects of intratracheal lidocaine spray on circulatory responses to endotracheal intubation]. AB - The effect of intratracheal lidocaine spray (0.5, 1.0, 2.0 mg.kg-1) on blood pressure and heart rate changes to endotracheal intubation was evaluated in 20 ASA I-II patients. After thiamylal induction, 15 patients received lidocaine spray with LTA kit. Mean arterial blood pressure and heart rate were recorded for 10 min every 30 sec and analysis of plasma lidocaine concentrations were also performed. In the control group, mean arterial blood pressure increased significantly compared with the pre-anesthetic values for one min, and with all spray groups at one min after intubation. Heart rate increased significantly at 30 sec after intubation only in the control group. Since the plasma lidocaine concentrations at intubation were below 1.5 micrograms.ml-1, we conclude that intratracheal lidocaine spray depresses the circulatory response to intubation by its local surface analgesic effect. PMID- 2255038 TI - [Anesthetic considerations for hepatic resection using veno-venous bypass]. AB - Anesthetic experience of 4 cases of hepatic resection using veno-venous bypass was reported. Non-forced bypass (passive shunt) was used in case 1. Hepatic resection was performed while supporting hemodynamic stability during the subsequent anhepatic phase using pump-driven veno-venous bypass (active shunt) in case 2-4. Various problems arose in each case. In the non-forced bypass case, hypotension during the bypass created a problem; whereas, hypothermia was pronounced during bypass in the pump-driven bypass cases. Massive transfusion due to bleeding, hypocalcemia, and unintentional hypothermia after veno-venous bypass precipitated heart failure. Attention should therefore be directed toward, (1) preparation for massive transfusion, (2) measurement and correction of the plasma calcium ion concentration, (3) maintenance of body temperature, and (4) hemodynamic control with a Swan-Ganz catheter and an inferior vena cava catheter. Extracorporeal bypass using a pump-driven veno-venous bypass (Bio-pump) and splanchnic decompression system via the portal system appear to be advantageous. PMID- 2255039 TI - [Cardiovascular changes after intubation and at the time of incision during nitrous oxide-oxygen anesthesia with epidural buprenorphine]. AB - The cardiovascular changes after intubation and at the time of incision under nitrous oxide-oxygen anesthesia with epidural buprenorphine (Bn) were examined. The subjects were 56 patients who underwent abdominal surgery. The patients were divided into two groups in terms of the epidural drugs used, i.e., group I (Bn 0.2 mg + saline 9 ml, n = 31) and group II (Bn 0.2 mg + 1% lidocaine 10 ml, n = 25). The systolic pressure increased significantly (P less than 0.05) to 169 +/- 29 mmHg (mean +/- SD) after intubation and to 162 +/- 28 mmHg after incision in group I, with no decrease in blood pressure during the non-stimulation period. In group II, although there was a significant decrease in blood pressure to 114 +/- 24 mmHg just before incision (P less than 0.05), no elevation of blood pressure was noted after intubation or incision. There was no significant difference between groups I and II with regard to the heart rate and respiratory rate. We were unable to block the cardiovascular reaction after intubation and incision under nitrous oxide-oxygen anesthesia with epidural Bn, requiring local anesthetics or volatile anesthetics. This method, however, is useful for patients in whom a fall of blood pressure should be avoided, e.g., for those with hypovolemia. PMID- 2255040 TI - [Changes in the intracranial pressure dynamics with head-down tilt in cats]. AB - To determine changes in the intracranial pressure dynamics under the condition of head-down tilt, the pressure-volume relationship in the cranial cavity as well as changes in intracranial pressure were studied experimentally in 31 cats. The animals were divided into three groups; with the horizontal, with the head-down and one with the head-up position. In each group the pressure volume index (PVI) and cranial cavity compliance (C) were examined under controlled respiration. The following results were obtained. (1) The values of PVI and C were significantly greater in the head-down tilt group as compared to those in the other groups, in spite of the increase in intracranial pressure level. (2) In the situations of craniospinal blockade by epidural ligation of spinal cord at C2 level, the PVI and C were also higher in the head-down tilt group than in the horizontal group. These results indicate that the pressure buffering capacity is increased with head-down tilt with respect to intracranial volume loading. It appears that the buffering mechanism does not depend on movement of the cerebrospinal fluid, but on the increased cerebral venous vascular bed with the communication between extracranium and intracranium. PMID- 2255042 TI - [Effects of sevoflurane and enflurane on isometric tension and maximum velocity of shortening in glycerinated guinea pig masseter muscles]. AB - To study the effects of inhalation anesthetics on the contractile system of masseter muscles, the Ca2+ concentration-isometric tension relationship and the maximum velocity of shortening were investigated in glycerinated guinea pig masseter muscles under the presence and absence of sevoflurane (10 mg% and 100 mg%) or enflurane (10 mg% and 100 mg%). Relative isometric tensions increased sigmoidally with an increase in Ca2+ concentration in all groups. K1/2 (pCa at the half maximum activated tension) was 6.53 in the control (absence of the anesthetics) and about 6.70 in the experimental groups under anesthetics regardless of the concentrations of anesthetics. The isometric tensions at higher Ca2+ concentrations were reduced by enflurane dose-dependently. They were also reduced by the low concentration of sevoflurane but increased by its high concentration. The maximum velocity of shortening was not influenced by these anesthetics (100 mg%) as far as the Ca2+ concentration was constant (pCa 6.36 or 5.94). These results suggest that in the masseter muscle, sevoflurane and enflurane alter the Ca2+ affinity in troponin C for actin filaments without changing the cross-bridge turnover rate. PMID- 2255041 TI - [Relationship between molecular structure of halogenated methane compounds and their hypotensive effect in rats]. AB - In this study gases of twelve halogenated methane compounds were administered by inspiration to Wistar rats in order to elucidate the relationship between molecular structure of the compounds and their hypotensive effect, and to develop new inhalational circulatory control agents. The correlation between the hypotensive effect of the compounds evaluated from the experimental data and computed van der Waals volume as well as surface area following molecular mechanics calculations of structure and energy, was investigated. The results showed that the compounds with van der Waals volume and surface area more than 73 A3 and 100 A2, respectively, had the hypotensive effect. In conclusion, our data suggest that the hypotensive effect of inhalational agents requires greater molecular sizes than regular ones. PMID- 2255043 TI - [Ketamine infusion for control of pain in patients with advanced cancer]. AB - The effect of ketamine infusion to control the intractable pain which had not responded to ordinary procedures in 12 patients with advanced cancer were evaluated. Ketamine 250 mg or 500 mg in 500 ml of transfusion fluid with or without 10 to 20 mg of droperidol was administered intravenously at the rate of 3 to 20mg of ketamine per hour. The pain scores by VAS in most of the patients decreased significantly with an averaged value of 8.3 before the treatment to 1 during the procedure. The durations of this therapy lasted from over 6 hours to 48 days. Slight disorientation in one patient and drowsiness in 5 were seen during the infusion. No cardiovascular or respiratory complications were noted. These results indicate that ketamine infusion is a useful therapeutic procedure to treat cancer pain which resist ordinary pain therapies. PMID- 2255044 TI - [Effects of lactation on pregnancy induced analgesia during the postpartum period in rats]. AB - Activation of an endogenous opioid system has been associated with an elevation in pain threshold during late pregnancy and the early postpartum period in rats. It is well established that endogenous opiates are involved in the physiological regulation on prolactin secretion. This study examined the influence of lactation on pregnancy-induced analgesia during the early postpartum period in rats. Three tests (colorectal distension, tail-flick and hot-plate) were used to assess each animal's response to painful stimuli. After determining pregnant baseline values, one group of rats (lactating, n = 21) were mated and retested on Day 7 and 21 of gestation and 1, 3, 5, 7 and 14 days after parturition. A non-lactating group of animals (n = 14) whose pups were removed immediately after delivery was tested in the same manner. On Day 21 of gestation significantly higher thresholds and longer latencies were observed. On Day 1 and 3 in both lactating and non lactating rats, the values were still elevated. No significant difference was observed during the early postpartum period between the two groups. This study confirms the existence, in rats, of pregnancy-induced analgesia late in pregnancy and the early postpartum period. The analgesia during the early postpartum period is not influenced by lactation. PMID- 2255045 TI - [Clinical investigation of flumazenil in reversing the respiratory effects of diazepam]. AB - Eight patients (ASA I-II) scheduled for a minor surgery under lumbar epidural or spinal anesthesia were studied. The patients were sedated with approximately 0.2 mg.kg-1 of bolus injection followed by 0.2 mg.kg-1.min-1 of continuous infusion of diazepam. In order to evaluate the reversing effects of 0.2 mg of flumazenil on the respiratory effects of diazepam, the following parameters were examined at three points, namely 1) control period, 2) during infusion of diazepam, and 3) ten minutes following injection of flumazenil; tidal volume, respiratory frequency, minute volume, inspiratory time/total time of breath (Tl/Tt) and %RC with a respiratory inductive plethysmograph, ventilatory response to carbon dioxide using a modified Read's rebreathing method. We found that with flumazenil, tidal volume and the slope of the ventilatory response curve to carbon dioxide increased and arterial carbon dioxide tension decreased. However, minute volume, respiratory frequency, Tl/Tt and %RC were unchanged with flumazenil. Flumazenil did not change other clinical features and did not produce any abnormal data in laboratory examination. We conclude that flumazenil reverses the respiratory effects of diazepam at least for ten minutes following its injection without producing any complications and side effects. PMID- 2255046 TI - [Total intravenous anesthesia with continuous infusion of midazolam--study on plasma levels of midazolam and catecholamines]. AB - Total intravenous anesthesia was performed with continuous infusion of midazolam and bolus injection of fentanyl. A bolus injection of midazolam 0.3 mg.kg-1 was followed by an infusion regimen with an initial infusion rate of 0.68 mg.kg-1.hr 1 for 15 min followed by a maintenance infusion of 0.125 mg.kg-1.hr-1 and infusion was stopped at about 30 min before the end of operation. Fentanyl and pancuronium were injected as required. Nicardipine was given for intraoperative hypertension. Plasma concentrations of epinephrine and norepinephrine decreased significantly at 10 min after induction, but increased significantly during operation. Therefore, this anesthetic method was considered not to be so deep. Plasma concentrations of midazolam were higher than 200 ng.ml-1 during operation. After discontinuation of midazolam infusion, its concentration decreased quickly, and the elimination half life of midazolam was 1.675 +/- 0.2807 hr. The value was not so large as we had anticipated. Total intravenous anesthesia with continuous infusion of midazolam and bolus injection of fentanyl is thought to produce light anesthesia. Plasma concentration of midazolam decreased quickly. PMID- 2255047 TI - [Anesthetic management of a patient with Sjogren's syndrome and pulmonary fibrosis]. AB - We described an anesthetic management of a 63 year old man complicated with Sjogren's syndrome and pulmonary fibrosis. Sjogren's syndrome is characterized by pathological dryness of the mouth, cornea and other exocrine glands. Anesthesia was induced with thiopental and the trachea was intubated smoothly following intravenous succinylcholine. Anesthesia was maintained with enflurane in nitrous oxide and oxygen. Intraoperative muscle relaxation was adequately obtained by pancuronium. Before and during anesthesia, atropine and other drying agents were avoided. Physiological saline solution was instilled on the eyes every ten minutes against dryness. A heat and moisture exchanger (Humi-Vent) was used to maintain high moisture of the respiratory tract. Anesthesia was carried out successfully. PMID- 2255048 TI - [Anesthesia for a patient with spinocerebellar degeneration who developed atrioventricular block]. AB - A 54-year-old female with a history of spinocerebellar degeneration (SCD) and myoma uteri had general anesthesia for the abdominal total hysterectomy. Though the operation was uneventfully performed, various atrioventricular blocks occurred. These might be related to the SCD. Hypertonic state of the vagus was considered to be the quite possible cause of the block. Myocardial degeneration associated with the SCD was also an undeniable factor of the block. No arrhythmia occurred and symptoms of the SCD were not aggravative after the anesthesia and the patient was discharged uneventfully. PMID- 2255049 TI - [Application of fuzzy algorithms for ventilatory control during clinical anesthesia]. AB - A computer program, which calculates the required minute volume using fuzzy set rule incorporating the authors' clinical experiences, was developed to keep a stable PCO2 during anesthesia, and its clinical usefulness was examined on 30 consecutive patients. The program requires the value of end-tidal CO2 concentrations at present, and 5 minutes before, and arterial-end-tidal CO2 tension difference (aEDCO2), and generates the adjustable value of minute volume to maintain the constant PaCO2 (acceptable range; 37 to 33 mmHg). Twenty-three cases were successfully controlled after adopting the calculated minute volume, which closely coincided with our clinical experiences. Seven cases, on the other hand, did not show the anticipated PaCO2 change, because of incidental leakage of endotracheal cuff (2 cases), larger aEDCO2 than the expected value of 4 mmHg (4 cases), or mild pulmonary edema (1 case). It has become clear that in the steady anesthetized patients, the program based on the authors' clinical experiences, which was made possible with the concept of fuzzy set rule, can be used to control the PaCO2 within the strict range during variable anesthetic situations. PMID- 2255051 TI - [The history of spinal anesthesia in Japan (7)--1946-1988]. PMID- 2255050 TI - [Treatment of chronic retinal artery obstruction with stellate ganglion block and electric acupuncture]. AB - A 56-year-old man (160 cm, 64 kg) having right visual field defect due to obstruction of the central retinal artery for 6 months was treated with stellate ganglion block and electric acupuncture. His visual field improved slightly immediately after preliminary treatment with stellate ganglion block and electric acupuncture judging from perimeter recording and his complaints. Stellate ganglion block on every day and electric acupuncture on every other day were performed for 10 days and there after these treatments were done two times a week. Twenty days after starting the treatment, his visual field improved on his perimeter examination. We discussed that the cause of improvement was activation of slept cone cells which needed more energy for activation than rod cells by increasing retinal blood flow with stellate ganglion block and electric acupuncture. We recommend vasodilating treatments such as stellate ganglion block and electric acupuncture for visual field defect due to obstruction of central retinal artery even in chronic state. PMID- 2255052 TI - [Reduction of erythrocyte membrane band 4.2 protein in patients with obstructive jaundice]. AB - Alteration of erythrocyte membrane proteins was studied in patients with obstructive jaundice in comparison with healthy controls. Analysis of the erythrocyte membrane proteins by SDS-PAGE revealed a slightly reduced protein 4.2 (MW 72 kDa). The erythrocytes with reduced protein 4.2 contained normal amounts of all other membrane proteins. In this study, it was demonstrated that the reduction of 4.2-protein is a common alteration in abnormal erythrocytes, target cells, and is observed in obstructive jaundice. PMID- 2255053 TI - [Elevated levels of cytokines in plasma from patients with disseminated intravascular coagulation]. AB - We measured blood concentrations of tumor necrosis factor (TNF), interleukin-1 beta (IL 1-beta), soluble interleukin 2 receptor (s-IL 2r), and interferon alpha (IFN alpha) in 30 patients with disseminated intravascular coagulation (DIC) and compared the results to those of 25 patients without DIC. Plasma levels of TNF, IL 1-beta, and s-IL 2r were higher in patients with DIC than in those without DIC. In one case of acute promyelocytic leukemia, plasma levels of TNF and IL-1 beta increased at the onset of DIC but decreased upon DIC improvement. These findings suggest that activation of the immune system is involved in the development of DIC. However, these concentrations were not markedly increased in patients with leukemia, although blood TNF and s-IL 2 r were markedly elevated in patients with solid cancers. Especially in patients with solid cancers, hyperactivation of the immune system may cause an increase in blood TNF and IL-1 beta and the development of DIC. PMID- 2255054 TI - [Autologous bone marrow transplantation in children with acute leukemia]. AB - Eight children with acute leukemia were treated with chemoradiotherapy or high dose chemotherapy followed by infusion of autologous marrow unpurged or purged mainly with monoclonal antibodies. Four were treated in their first remission, three in their second remission, and one in the fourth remission. Patients were isolated in laminar air flow rooms with sterile conditioning. Infused mononuclear cells ranged from 1.0 to 3.8 x 10(7)/kg. Hematologic engraftment was obtained in five patients. The other three patients, who were treated with monoclonal antibody or drug, received unpurged back up marrow because of delayed bone marrow reconstitution. Two recovered, but one died before engraftment. Hematologic recovery was delayed after autologous bone marrow transplantation. The median time to achieve 1,000 leukocytes/microliters, 500 neutrophils/microliters, and last platelet transfusion was 36 days (12-90), 36 days (12-90), and 70 days (39 214), respectively. Moreover, further increases beyond these levels remained unusually slow, especially in platelets. Two of eight patients relapsed at 5 and 15 months and the other patient died of interstitial pneumonitis. Actuarial disease free survival was 62.5%. There was a trend toward improved disease free survival for patients transplanted in the first remission (100%). PMID- 2255055 TI - [Induction of differentiation of myelomonocytic leukemia cells by mitoxantrone]. AB - We studied the effect of mitoxantrone (MIT) on the proliferation and differentiation of murine myelomonocytic leukemia cell line WEHI-3B (D+), human myelocytic leukemia cell line HL-60 and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). In a liquid culture, growth inhibition and differentiation of WEHI-3B (D+) cells to mature myeloid cells and a reinforcement tendency of the induction of nitroblue tetrazolium reducing capacity as well as of ASD chroloacetate esterase staining was observed by the treatment with MIT. Fresh ANLL cells classified as M4 were induced by MIT to undergo terminal differentiation to macrophage-like cells. Since at concentrations of WEHI-3B (D+) cells of less than 1 x 10(5)/ml induction of differentiation was observed due to MIT, it is suggested that its mechanism of action differs from that of the induction of differentiation by granulocyte colony-stimulating factor and is due to the direct action of MIT. PMID- 2255057 TI - [Smoldering leukemia with pyoderma gangrenosum]. AB - A 76-year-old male admitted to Surugadai Nihon University hospital complaining of general fatigue, slight fever and anorexia. The laboratory examination revealed anemia and an appearance of a few myeloblasts and 7% of monocytes in the peripheral blood. The nucleated cell count was 2 x 10(4)/microliters with 43% myeloblasts in the bone marrow aspirate. He was diagnosed as acute myelomonocytic leukemia. He did not receive any chemotherapy for leukemia because of his old age and smoldering disease. Pyoderma gangrenosum developed in the left submandibular and axillary regions about 6 months later. Three more month later, significant increase of myeloblast was recognized in the peripheral blood and the bone marrow. It has been reported that pyoderma gangrenosum precedes a remarkable increase of leukemic cells in the patients with acute leukemia in complete remission and with myelodysplastic syndrome. In our case, to, the same process was strongly suggested. PMID- 2255056 TI - [Weekly CHOP chemotherapy in the treatment of intermediate-grade non-Hodgkin's lymphomas--cooperative group study by seven institutes]. AB - Between 1985 and 1988, 49 previously untreated patients with intermediate-grade non-Hodgkin's lymphoma (LSG classification large cell 35 including 11 large cell immunoblastic by Working Formulation, medium-sized cell 7, mixed 7) were treated with the Weekly CHOP regimen (three successive weekly administration of cyclophosphamide, doxorubicin, vincristine and prednisolone) as a cooperative group study by seven institutes (Nagoya Lymphoma Study Group). Complete remission was achieved in 63.3% with Weekly CHOP alone and finally in 79.6% after the addition of radiotherapy and/or combination chemotherapies including etoposide, methotrexate, procarbazine, bleomycin. Patients with T cell phenotype, high grade PS and the presence of bulky mass had significantly lower rates of CR. After a median follow-up 36 months Kaplan-Meier estimates showed that overall survival was 60.4%, disease-free survival 51.4% and relapse-free survival 64.6%. The major toxicities were alopecia, leukopenia, infection, neuropathy and gastrointestinal symptoms. No treatment-related deaths were observed. Survival was adversely affected by high LDH level, poor PS, T cell phenotype, the presence of B symptoms and the bulky mass. But these characteristics gave no significant effects on relapse rate and relapse-free survival. Thus, Weekly CHOP is an effective treatment for intermediate-grade NHL. PMID- 2255058 TI - [Essential thrombocythemia transformed to acute myeloblastic leukemia]. AB - A 48-year-old woman was referred to Tohoku University Hospital in November 1981 because of leukocytosis pointed out in a group examination. At that time white blood cell count was 26.8 x 10(3)/microliters with no blasts, platelet count 268.0 x 10(4)/microliters and hemoglobin 11.4 g/dl. Bone marrow aspirates showed marked increase of megakaryocytes (15,900/microliters). Bone marrow chromosome analysis revealed 46, XX, -18, +mar without Ph1 chromosome, and DNA analysis showed no bcr rearrangement. She was diagnosed as having essential thrombocythemia and was treated with busulfan. On November 1986, she developed remarkable leukocytosis with leukemic blasts. White blood cells reached 153 x 10(3)/microliters with 33% blasts. Her blasts were positive for peroxidase staining, but negative for platelet peroxidase on electron microscopic study and platelet specific glycoproteins. A diagnosis of acute myeloblastic leukemia (M2) was made. The patient received various combination chemotherapy, which was ineffective, and she died due to pneumonia on June, 1989. In Japan, there has been reported only 8 cases of essential thrombocythemia transformed to acute leukemia. The clinical pictures of these 9 cases were discussed. PMID- 2255059 TI - [Administration of recombinant erythropoietin to a patient with malignant lymphoma who refused blood transfusion]. AB - A 30-year-old female patient with malignant lymphoma was admitted to the hospital because of large mass in the left pelvic cavity and of severe anemia. Since she had refused blood transfusion (Jehovah's witness), recombinant human erythropoietin (Epo) was used together with both chemotherapy and irradiation; this led to rapid recovery of the anemia and marked reduction of the mass volume. These findings may suggest the possible application of Epo administration as a supportive therapy in treatment of malignancy. PMID- 2255060 TI - [Sideroblastic anemia associated with adenine phosphoribosyltransferase deficiency]. AB - We report a case of acquired idiopathic sideroblastic anemia associated with adenine phosphoribosyltransferase (APRT) deficiency. A 72-year-old male had been troubled with urolithiasis since his teens. In 1984, he was referred to us because of chronic renal failure and anemia. He was diagnosed as having sideroblastic anemia and required red cells transfusion regularly. In June 1989, he was admitted to our hospital because of cerebral infarction. Peripheral blood analysis showed pancytopenia. Bone marrow aspiration revealed hypercellularity with 36.2% erythroblasts, and 18.5% ringed sideroblasts of all nucleated cells. According to the FAB classification, a diagnosis of refractory anemia with ring sideroblasts was made. As his urinary stone consisted of 2, 8-dihydroxyadenine by analysis of infrared spectrum, genetic and enzymatic studies were performed. These studies indicated APRT deficiency. He died of pneumonia accompanied with progressive renal failure on August 9, 1989. PMID- 2255061 TI - [Hemolytic anemia and acute renal failure caused by blood transfusions]. AB - We report a case of 33 years old woman who developed hemolytic anemia after blood transfusion. In this case no abnormalities were observed by the cross-match test performed before blood transfusion. She was undergone the surgical resection of liposarcoma of her right arm in June, 1984 and 8 units of the concentrated red blood cells were transfused during the operation. During the following 2 months 13 units of the concentrated red blood cells were transfused. Immediately after blood transfusion, she developed icterus and oliguria and was diagnosed acute renal failure associated with hemolytic anemia. At this time we examined the antigen type of her red blood cells and of three donors' red blood cells which had been given to her. As the result, either C (Rh-hr), Pi (P), Lea (Lewis), Fyb (Duffy) antigens were found in some of donors' RBC, but no such antigens were detected in her RBC. The half life span of RBC measured using 51Cr labeled RBC was 6.2-14.5 hours, in respect of the antigen-positive RBC, where as it was 49.4 hours in the RBC without the antigens. It is more likely that the blood transfusion was the cause of hemolytic episode in this case, because the half life span of the donors' RBC was extremely shortened, compared with that of her own blood which was 16 days. PMID- 2255062 TI - [Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis]. AB - A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia. PMID- 2255063 TI - [Administration of haptoglobin in ABO incompatible bone marrow transplantation]. AB - Haptoglobin was administered i.v. in 2 cases of ABO incompatible bone marrow transplantation for the prevention of hemoglobinuria due to acute hemolysis. The first case was a 25-year-old woman with severe aplastic anemia. The transplantation was both major and minor mismatch, where the donor was type A and the recipient was type B. The second case was a 31-year-old man with chronic phase of chronic myelogenous leukemia. The transplantation was major mismatch, where the donor was type B and the recipient was type O. After the administrations of haptoglobin 8,000 units we transfused bone marrow infusates from which incompatible erythrocytes were removed. Though prominent hemoglobinemia was observed in both cases, the serum haptoglobin values were not saturated and hemoglobinuria was not detectable. Haptoglobin appears to be useful for the prevention of acute renal failure associated with acute hemolysis in ABO incompatible bone marrow transplantation. Intravenous haptoglobin supplement therapy makes transplantation safer and may contribute to improve the recovery rate of total nucleated bone marrow cells after the erythrocyte depletion without worrying much about their contamination. PMID- 2255064 TI - [Long-term remission of a case of Burkitt's lymphoma accompanied by cardiac tamponade treated by surgical resection and intensive chemotherapy]. AB - A 26-year-old woman was admitted to our hospital because of abdominal mass. She became ileus and an emergency operation was consequently performed. A histological examination of the abdominal tumor indicated proliferation of undifferentiated lymphoblasts with intermingled histiocytes so called "starry sky appearance". The diagnosis was Burkitt's lymphoma. On the 4th post-operative day, a cardiac tamponade became evident. The pericardial effusion contained many lymphoblasts and the diagnosis was pericarditis due to the invasion of lymphoma cells. The pericarditis was successfully treated by infusion of doxycycline into the pericardial space following drainage. The patient responded to systemic chemotherapy with complete remission. 7 courses of systemic chemotherapy along with intrathecal infusions for CNS prophylaxis were subsequently carried out. A state of complete remission has continued for more than 13 months. Cardiac tamponade accompanied by Burkitt's lymphoma is quite rare and has not ever been reported in Japan in our knowledge. The efficacy of surgical treatment before systemic chemotherapy and the series of intrathecal infusions for CNS prophylaxis was demonstrated in this case. PMID- 2255065 TI - [Rapid progression of systemic amyloidosis after high-dose corticosteroid therapy in multiple myeloma]. AB - A number of different combination regimens including high-dose corticosteroids (HDCS) have been widely used in an attempt to achieve better results for relapsed or alkylating agent-resistant multiple myeloma (MM). A major complication of these regimens is commonly said to be infection. In addition, we have had occasion to point out that a rapid progression of systemic amyloidosis can be one of serious complications of HDCS therapy in MM. The patient, born in 1940, was diagnosed of having Bence Jones (BJ) type MM in 1987. The conventional therapy including alkylating agents and interferon-alpha induced a partial remission of 22 months' duration. After the relapse, 2 courses of vincristine, adriamycin plus high-dose dexamethasone resulted in a reduction of the excreted amount of urinary BJ proteins with symptomatic improvement. However, the following clinical features indicating systemic amyloidosis occurred in succession within 2 months after beginning the therapy: submandibular swelling, giant tongue, shoulder pad sign, carpal tunnel syndrome, low voltage on ECG and recurrent diarrhea. The biopsy specimens from the submandibular gland revealed amyloid deposition. In the present case, a rapid progression of systemic amyloidosis is supposed to be attributable to the HDCS therapy. The possible mechanism of enhancement of amyloidosis by HDCS therapy is discussed. PMID- 2255066 TI - [A long-term observation of development from monoclonal gammopathy of undetermined significance (MGUS) into primary amyloidosis]. AB - The term, "monoclonal gammopathy of undetermined significance (MGUS)" is used because it is not known at the time of recognition whether the M-component will remain stable or will develop into multiple myeloma (MM) or related disorders. Recently, we have encountered a case of MGUS in which a diagnosis of primary amyloidosis (PA) was made more than 10 years after the recognition of an M component in the serum. A 64-year-old man presented in 1979 for evaluation of monoclonal gammopathy. The level of M-component (IgG-lambda) in the serum was 1.6 g/dl. The urinary Bence Jones proteins (BJP) were negative. Bone marrow aspirate contained 9.8% plasma cells. Skeletal surveys were normal. A diagnosis of MGUS was made. In 1982, a trace amount of BJP was detected in the urine. Since 1988, carpal tunnel syndrome, angina pectoris and congestive heart failure developed in succession. In November 1989, the patient was admitted to Kyoto University Hospital for examination. Serum electrophoretic pattern remained unchanged. The excreted amount of urinary BJP was less than 0.3 g/day. Bone marrow aspirate contained 5.4% plasma cells. Histologic studies of bone marrow biopsy specimens revealed amyloid deposition. An echocardiogram was thought to reveal amyloidosis. Significant uptake of Tc-99m (V) DMSA was found in carpal regions, kidneys and heart. A diagnosis of PA was made. It is noteworthy that the development of PA did not accompany an increase in the serum M-component. An early diagnosis of PA as well as MM should be kept in mind in the follow-up study of patients with MGUS. PMID- 2255067 TI - [Successful therapy of Ph1 positive chronic myelocytic leukemia with oral form of etoposide]. AB - A 33-year-old female was diagnosed as having chronic myelocytic leukemia (CML) with Philadelphia (Ph1) chromosome and breakpoint cluster region (bcr) rearrangement. Physical examination revealed a huge splenomegaly and laboratory data showed WBC 490 x 10(3)/microliter and NAP score 44. She was treated with hydroxyurea, alpha-interferon, or busulfan, but severe adverse reaction such as skin rash, fever, and arthralgia, which allowed the therapy discontinue was occurred. When the patient was treated with the oral form of etoposide, a semisynthetic podophillotoxin, the number of leukocyte has been successfully maintained less than 10 x 10(3)/microliters at the dose of 50-100 mg/day and splenomegaly completely disappeared. Although Ph1 chromosome was unchanged in the percentage after the therapy for 5 months, etoposide may be effective agent for a chronic or accelerated phase of CML. Alopecia which was reversible and well tolerable was the only side effect of the drug. PMID- 2255068 TI - [Low-dose danazol therapy in idiopathic thrombocytopenic purpura]. AB - Danazol was administered orally at a dosage of 50 mg/day to 17 patients (11 females and 6 males) with idiopathic thrombocytopenic purpura refractory to steroids and/or splenectomy. The patients had not been treated with conventional dosages of danazol. The drug was suspended in four patients because of adverse effects of danazol. In 13 patients (8 females and 5 males, mean age 44 y. o.) who received the danazol therapy for more than 6 months, there were no patients with an excellent response, and one patient had a good response to the therapy. The rest of the patients did not respond to danazol. PMID- 2255069 TI - [Improvement of the anemia associated with multiple myeloma and renal dysfunction by recombinant human erythropoietin]. AB - Recombinant human erythropoietin was administered to an anemic patient with multiple myeloma (IgD, lambda type) and renal dysfunction who had been dependent on blood transfusions. Three thousand units of the recombinant human erythropoietin was given intravenously three times a week. Thereafter transfusion requirements, hemoglobin level, and reticulocyte responses have been monitored. An increase in hemoglobin level and reticulocyte counts was observed within 10 days and then further blood transfusion was not necessary. Neither organ dysfunction nor toxic effects were observed. The administration of recombinant human erythropoietin can be a new method to treat anemia associated with multiple myeloma and renal dysfunction. PMID- 2255070 TI - [Growth factors and cell transformation]. PMID- 2255071 TI - [bcl-2 gene involved in t(14;18) translocation]. PMID- 2255072 TI - [Amplification of protooncogenes]. PMID- 2255073 TI - [Gene regulation and proto-oncogenes]. PMID- 2255074 TI - [Chromosome translocation and gene rearrangement]. PMID- 2255076 TI - [Oncogenes and antioncogenes--progress in the study of molecular oncology and its clinical application]. PMID- 2255075 TI - [Application of polymerase chain reaction (PCR) to detect activated oncogenes]. PMID- 2255077 TI - [Dot hybridization with synthetic oligonucleotide; analysis of point mutation of c-ras genes]. PMID- 2255078 TI - [Single-strand conformation polymorphism analysis]. PMID- 2255079 TI - [Studies of oncogene expression at the cellular level by in situ hybridization]. PMID- 2255080 TI - [Detection of activated oncogenes by Southern blot analysis]. PMID- 2255081 TI - [Effective cell lines for detecting unknown oncogenes]. PMID- 2255082 TI - [Oncogenesis in transgenic mice]. PMID- 2255083 TI - [Mutation of RB gene in retinoblastoma]. PMID- 2255084 TI - [Transforming genes of DNA tumor viruses]. PMID- 2255085 TI - [The Krev-1 transformation suppressor gene]. PMID- 2255086 TI - [Tumor suppressor gene: p53]. PMID- 2255087 TI - [Structure of the s-myc gene involved in tumor suppression]. PMID- 2255088 TI - [Strategies for the isolation of tumor suppressor genes]. PMID- 2255089 TI - [Studies on tumor suppressor genes via microcell fusion]. PMID- 2255090 TI - [HBV gene products and c-myc transactivation]. PMID- 2255091 TI - [Transforming genes of human adenoviruses]. PMID- 2255092 TI - [Clinical application of molecular oncology]. PMID- 2255093 TI - [c-myc gene]. PMID- 2255094 TI - [Functional characterization of c-myb gene product]. PMID- 2255095 TI - [Oncogenes and anti-oncogenes in carcinogenesis]. PMID- 2255096 TI - [Human ret proto-oncogene]. PMID- 2255097 TI - [c-src-related genes]. PMID- 2255098 TI - [c-abl gene and bcr-abl fused gene in Ph1-positive leukemias]. PMID- 2255099 TI - Present status of research on cancer chemoprevention in Japan. AB - The activities of the research group on cancer chemoprevention supported by the Ministry of Health and Welfare of Japan are summarized. Since the research on cancer chemoprevention is quite new in Japan, this paper describes the present status of the development of possible cancer preventive agents. Acyclic retinoid (E-5166) and sarcophytol A encourage further studies. New inhibitory compounds of experimental carcinogenesis, such as cryptoporic acid, oleanolic acid, mokko lactone and ursolic acid were isolated from plants. The importance of the keen collaboration between natural product chemists and clinicians for further meaningful progress in this research field has been emphasized. PMID- 2255100 TI - Descriptive epidemiology of subsites of cancers of the liver, biliary tract and pancreas in Japan. AB - Recent time trends (1979-1987) and geographical distributions in mortalities from subsites of cancers of the hepato-biliary-pancreatic system have been investigated on the basis of the vital statistics of Japan. The corrected age adjusted mortality rates (CAAMRs) were calculated to eliminate the influence of the proportion of subsite-unknown cancers. During the above period, the CAAMR for intrahepatic bile duct cancer increased by a relatively high extent (2.0-fold in males and 1.67-fold in females), and those for cancers of the gallbladder, extrahepatic bile duct and pancreas (head and other parts) increased to a moderate extent (1.2-1.4-fold). The CAAMR for primary liver cancer showed an increasing trend in males and a decreasing trend in females. The CAAMR for cancer of the ampulla Vater changed little during the period. A clear cluster of prefectures with high CAAMRs was observed in the northern part of Japan for cancers of the extrahepatic bile duct and pancreatic head. Clusters of prefectures with high CAAMRs for cancer of the gallbladder and ampulla Vater were observed in the mid-northern part of Japan, especially on the Japan Sea side. The CAAMR for primary liver cancer was high in the Island of Kyushu and some western parts of Japan, and low in the northern part of Honshu Island. No clear clusters of prefectures with high CAAMRs were observed for cancers of the intrahepatic bile duct and pancreas, other than for the pancreatic head. PMID- 2255101 TI - Surgical treatment of metastatic renal cell carcinoma. AB - The survivals of 174 patients who underwent nephrectomy for renal cell carcinoma were analyzed to evaluate the influence of the surgical treatment of metastases on their prognosis. For 34 of the 174 patients, surgical resections of the metastases were performed concurrently with nephrectomy. For 38 patients, 44 surgical resections of metastases were performed in the follow-up period after nephrectomy. Apparently curative resections of metastases, at the time of nephrectomy or after nephrectomy, were significantly correlated with good survivals after surgery, irrespective of the number of metastatic foci. Aggressive surgical treatment was beneficial in patients with a longer tumor-free period after nephrectomy or with stable disease for about six months after surgical treatment, although this might simply be a reflection of a longer natural disease course in this specific group of patients. PMID- 2255102 TI - Urinary vanillylmandelic acid and homovanillic acid levels in randomly-sampled urine for the mass screening of neuroblastoma. AB - Employing 421 urine samples taken randomly from normal infants and 294 samples from infants with neuroblastoma, we investigated the application of values of vanillylmandelic acid (VMA), homovanillic acid (HVA) and square root of VMA2 + HVA2 to discriminate between patients and normal infants. The establishment of an HVA cut-off level is virtually impossible because of its low sensitivity. In contrast, VMA sensitivity is high, and that of square root of VMA2 + HVA2 is very similar to that of VMA although it includes HVA. Although VMA appears to be able to discriminate well, discrimination employing VMA alone would be dangerous because cases with normal VMA and abnormal HVA would be missed, especially in the first screening for which a mechanical discrimination is performed. Overlooking such cases can be avoided by the adoption of the function square root of VMA2 + HVA2. The present study suggests that the combined use of variables can be more effective than using them separately. PMID- 2255103 TI - Prognostic significances of estrogen and progesterone receptors in primary operable breast cancer. AB - Both estrogen and progesterone receptors have been determined in 613 primary breast cancer patients treated by radical mastectomy. At the cut-off value of 5 fentomoles (fmol) cytosol protein/mg for both receptors, patients with estrogen or progesterone receptor-positive breast cancer showed significantly favorable disease-free, overall and post-recurrence survival curves to those of receptor negative breast cancer patients. In the patient subgroups: premenopausal, stage III, more than four positive lymph node metastases, postoperative adjuvant tamoxifen therapy, a significantly favorable prognosis was recognized in either estrogen or progesterone receptor-positive patients. Both receptors are thought to be useful prognostic indicators for patients with advanced tumors or for those receiving postoperative adjuvant tamoxifen therapy. When the cut-off value was changed, the maximum significant difference in prognosis between receptor positive and receptor-negative patients was observed at 5 fmol cytosol protein/mg for the estrogen receptor or 10 fmol/mg cytosol protein for the progesterone receptor. A more detailed examination should be made on the cut-off values of both receptors. PMID- 2255104 TI - Evolution and progression in malignant lymphoma of Waldeyer's ring: histopathological and immunohistochemical studies of three cases of total tonsillectomy. AB - Histopathological and immunohistochemical studies were performed in three patients with malignant lymphoma of Waldeyer's ring (ML-WR) who underwent total tonsillectomies. Residual reactive follicles mixed with neoplastic follicles were present beneath the surface epithelium of the crypts at the base of the tonsils. The neoplastic follicles were growing expansively and fusing with each other until finally, the process resulted in a diffuse proliferation pattern. Both of the tumor and follicular center cells (FCCs) in the reactive follicles were positive for LN-1; accordingly, the ML-WR tumor cells were considered to originate from FCCs. Anti-S-100 positive follicular dendritic cells (FDCs) were much scarcer in the neoplastic follicles of the tonsils than in the neoplastic follicles of the lymph nodes. FDCs may have a role to play in regulating the proliferation pattern of tumor cells in ML-WR. PMID- 2255105 TI - Amelanotic malignant melanoma of the esophagus: case report and review of the literature. AB - A case of amelanotic malignant melanoma of the esophagus in a 76-year-old woman is reported. A whitish polypoid tumor, measuring 3 x 2 x 2.7 cm, surrounded by black pigmented mucosa, was detected in the middle intrathoracic esophagus. The tumor showed a lobulated surface lined by squamous cell layer, and had epithelioid and polyhedral cells forming alveolar clusters. Melanin pigments or stainability for the dihydroxyphenylalanine (DOPA) reaction were only observed in a few tumor cells. Junctional changes and mucosal melanosis, however, were found freely in the mucosa around the tumor. Many tumor cells showed a strongly positive immunohistochemical reaction for neuron specific enolase (NSE) and S100 protein. The patient died of widespread metastases six months after surgery. Further, a review of 106 reported cases of primary esophageal malignant melanoma, including 29 autopsies, was made; the melanomas were found to include 10 of amelanotic type, eight of which had been misdiagnosed at biopsy. Junctional changes could be found in the mucosa over or around the tumor, in four cases, and mucosal melanosis in one. Lymph node metastasis was the most frequently observed development at autopsy regardless of whether the tumor was amelanotic or melanotic. For correct diagnoses of melanomas of the amelanotic type, peripheral mucosal findings, such as junctional changes or melanosis, should be helpful; and, in order to obtain a good prognosis, a careful resection of the regional lymph nodes could prove valuable. PMID- 2255106 TI - Osteosarcoma arising from a multiple exostoses lesion: case report. AB - A case of osteosarcoma arising from a multiple exostoses lesion is presented. Poorly differentiated osteosarcoma occurred in a twelve-year-old girl's proximal tibia where an exostosis was confirmed from radiographs. We treated this patient with preoperative chemotherapy, thigh amputation and postoperative chemotherapy, but she died of multiple pulmonary metastases seven months after surgery. The osteosarcoma, complicated by multiple exostoses, had a very poor prognosis because it was resistant to various anticancer agents. PMID- 2255107 TI - Choriocarcinoma with brain metastasis: report on two cases with long-term survivals. AB - Choriocarcinoma is a potentially curable neoplasm. Although the presence of brain metastases worsens the ultimate prognosis, aggressive therapeutic intervention is sometimes justified for brain metastases of a potentially curable neoplasm. In the present clinical report, we present two cases of choriocarcinoma with brain metastasis manifesting neurological deterioration, and discuss treatment strategies. From the results of treatment, we conclude that surgical removal of the lesion, followed by chemotherapy combined with irradiation, should be the treatment of choice in patients with progressive neurological deterioration. PMID- 2255108 TI - Long-term survival after brain metastasis from endometrial cancer. AB - A case is reported of prolonged survival after radical hysterectomy for poorly differentiated adenocarcinoma of the endometrium and resection of metastatic carcinoma of the brain followed by radiation therapy. The 43-year-old patient has survived for seven years after hysterectomy and six years 10 months after excision of the brain metastasis. Our results show that the surgical excision of a single metastatic lesion of the brain with postoperative irradiation offers hope of prolonged survival in patients with a solitary brain metastasis and no evident systemic disease. PMID- 2255109 TI - Standardized mortality rates of cancer by prefecture in 1979-1981 and 1984-1986 in Japan. PMID- 2255110 TI - [A study on immunoglobulin A in human milk. Relationship between the amount of IgA and perinatal factors including food intake]. AB - The concentrations of IgA in human milk on the 5th or 6th day after delivery were measured in 117 women who delivered maturely, and the amount of IgA per 24 hours was calculated by multiplying the IgA concentration by the total milk volume of the same day. The relationship between the amount of IgA and perinatal factors, including food intake during the latter half of the pregnancy, were investigated. Subjects were divided into three groups (little, moderate, much) by the amount of IgA per 24 hrs and quantification theory II statistical analysis was applied to discriminate among the three groups using 13 factors concerning the perinatal period and food intake as explanatory variables. 1. The ratio of correct classification into the three groups was relatively high, suggesting that there is a relation between the amount of IgA in milk and perinatal and food intake factors. 2. Among the perinatal factors, the age, the gestation period and the number of experienced deliveries were effective for the amount of IgA. The obtained results showed that women 20-29 years old who had the first delivery after 38-40 weeks of gestation were liable to have the greatest amount of IgA in milk. 3. The amount of IgA of the women who ate less in the latter period of pregnancy compared with pre-pregnancy, or had a "less frequent intake of protein" was liable to be the greatest, and that of women with a "large volume" or "frequent protein intake" was liable to be greater than that of those with "the same volume" or "moderately frequent protein intake." The amount of IgA of the women with a "frequent intake of salted dried fish" was the greatest. The fact that the amounts of IgA of the women who "ate less" or had a "less frequent intake of protein" were liable to be the greatest was considered to show that toxemia or the tendency to near abortion or preterm delivery greatly affected the amount of IgA. PMID- 2255112 TI - Analysis of factors associated with birth weight. PMID- 2255111 TI - [Rate of incidence of divorce in birth cohorts classified by age difference between married couples]. AB - We examined the situation concerning divorce in Japan from the view-point of age difference between married couples using vital statistics from the year 1952 to 1985. Annual and cumulative divorce rates were introduced as rate of incidence of divorce. We studied these indices by age difference between couples in birth cohorts of husbands. Our conclusions were as follows: 1) The cumulative divorce rate was lower in early birth cohorts than in late birth cohorts. 2) The cumulative divorce rate for young adult couples (aged 20-30) was higher than that for middle-aged couples (aged more than 30) in every cohort. 3) The cumulative divorce rate was lowest when husbands were 1 to 4 years older than wives. This tendency was quite similar in different ages and cohorts. 4) The same conclusions were reached when the annual divorce rate was substituted for the cumulative divorce rate. PMID- 2255113 TI - [Sensory scaling of odor based on mathematical studies of rating words]. AB - Sensory scales are very important indicators for the evaluation of environmental odors, and of the effect of deodorizers. The purpose of this study is to examine reasonable methods of sensory scaling. For this purpose, the psychological values of rating words for odor intensity, odor hedonics and similarity were measured. The interval distances between categories of each scale were estimated in the method of successive categories as well. Results of this study are as follows. 1) The 6-step odor intensity scale, issued by the Environmental Agency, may be regarded as an ordinal scale, but not as an interval scale. The 9-step hedonics scale may be regarded as an interval scale. 2) Psychological values of rating words are not affected by the size and the number of category steps in the graphic scales applied to the judgements of their values. 3) The number of category steps needs to be determined based on the distribution of the psychological values. The meanings and the order of the rating words have to be clear. 4) In the construction of a numerical scale, the category values should accord nearly as possible with the psychological values of rating words. 5) In results from the method of successive categories applied to the measured values of odor intensity and similarity, interval distances between categories are unequal, and the interval distances are wide on both edges of the scale. In these cases, the values must be converted into "category values of stimuli." PMID- 2255114 TI - [Age-associated changes in antibody production of murine spleen cells]. AB - In the present work, we studied age-associated changes in murine immune functions. We estimated total antibodies and autoantibodies to single-stranded DNA (ss-DNA), double-stranded DNA (ds-DNA) histone and collagen in sera and culture supernatants of spleen cells from young and aged BALB/c, C57BL/6 and MRL/MpJ-(+/+) (MRL/n) mice. In MRL/n mice, the IgM class of the total antibody level in serum increased gradually to the maximum at 3 months of age, and then started to decrease. In contrast, the IgG class started to rise with age after the age of 9 months. Serum levels of IgM and IgG autoantibodies to DNA were dominant in MRL/n mice, and the IgG class started to increase in earlier stages of life than in BALB/c and C57BL/6 mice. Anti-DNA autoantibodies were produced in lipopolysaccharide (LPS)-stimulated cultures of spleen cells from BALB/c, C57BL/6 and MRL/n mice. The stimulatory effect of LPS on autoantibody production was significantly reduced by the addition of concanavalin A (Con A) to the LPS stimulated cultures. The Con A-induced suppressive activity increased with the donor age in MRL/n mouse spleen cells. On the other hand, total antibody production in LPS-stimulated cultures was not affected by the addition of Con A to the cultures. These results may suggest that IgG autoantibody-producing B cells increase with age in MRL/n mouse spleen cells, and that the suppressive activity on autoantibody production is selectively augmented. PMID- 2255115 TI - [Zinc and copper concentrations in breast milk and maternal serum in the postpartum period]. AB - This study reports the contents of Zn and Cu in the breast milk and serum of postpartum mothers, 17 primiparas and 20 multiparas, at one week and at one month after delivery. Results were as follows. 1. The mean content of Zn in the breast milk was 5.44 micrograms/ml at 1 week after delivery, and it decreased significantly (p less than 0.01) to 2.73 micrograms/ml at 1 month after delivery. 2. The mean content of Zn in serum was 0.66 microgram/ml at 1 week, and it increased significantly (p less than 0.01) to 0.84 microgram/ml, close to the normal level, at 1 month. 3. The milk Zn level at 1 week after delivery was about 8 times as high as the Zn in serum. There was a significant (p less than 0.05) negative correlation in Zn contents between milk and serum at 1 week after delivery, and there was no significant correlation in Zn contents between milk and serum at 1 month after delivery. 4. The mean content of Cu in breast milk was 0.55 microgram/ml at 1 week after delivery, and it decreased to 0.44 microgram/ml at 1 month after delivery. 5. The mean content of Cu in serum was 2.14 micrograms/ml at 1 week after delivery, and it decreased significantly (p less than 0.01) to 1.35 micrograms/ml, close to the normal level, at 1 month after delivery. 6. Concerning the Cu contents of milk and serum, there was not a significant correlation at 1 week after delivery, but a significant (p less than 0.05) positive correlation was found at 1 month after delivery. PMID- 2255116 TI - [Bone mineral contents of lumbar vertebrae in postmenopausal women--using a quantitative computed-tomography method]. AB - We measured bone mineral contents of lumbar vertebrae (L1, L2, L3, L4) in 58 post menopausal female volunteers (49-76 years old), using a quantitative computed tomography method. We investigated age-related changes of bone mineral content, and analyzed the relation of bone mineral content to vertebral deformity and to physical characteristics. The following results were obtained: (1) There were highly significant correlations and some significant differences among bone mineral contents of L1, L2, L3 and L4. (2) Bone mineral content showed an apparently linear decline with age. (3) A significant negative correlation was observed between bone mineral content and the central deformity index of the vertebral body, but not for the anterio-posterior deformity index. (4) It was difficult to verify an association of bone mineral content with physical characteristics, such as height, weight, and body mass index. PMID- 2255117 TI - [Determination of Mg and Zn contents of Naruto "wakame" (Undaria pinnatifida)]. AB - The contents of Mg and Zn in the sea-weed "wakame" were determined and compared at different growth stages, in different parts, for different root cultivation intervals, and in processed foods. The results obtained were as follows: 1. Mg (2.09-2.60 g/100 g) and Zn (8.00-10.76 mg/100 g) contents were independent of growth stage with the exception of Zn (29.00-35.78 mg/100 g) in the natural young "wakame". 2. The mineral contents of leaves, stipes, fruiting bodies and rhizoids of "wakame" at different growth stages were determined. The contents of Mg (1.00 2.36 g/100 g) and Zn (3.93-12.01 mg/100 g) were richer in leaves and stipes than in fruiting bodies and rhizoids. 3. Densely cultured "wakame" showed higher contents of Zn (6.73 mg/100 g) than thinly cultured plants (5.99 mg/100 g), and Mg content was not affected by changes in environmental conditions. 4. The Mg/Ca ratios reached a maximum in the stipe (3.3) and at fruiting bodies (2.9) in the middle stage, and in the base of the stipe of the mature plant (3.5). 5. Contents of the minerals in processed foods were determined. "Suboshi" was rich in Mg (1.07 +/- 0.42 g/100 g), and "Haiboshi" was rich in Zn (10.90 +/- 1.20 mg/100 g). The mineral contents in "Enzo" were small. PMID- 2255118 TI - [32nd Congress of the Japan Geriatric Society. Kochi City, November 15-17, 1990. Abstracts]. PMID- 2255119 TI - Prevalence of human alveolar echinococcosis in Hokkaido as evaluated by western blotting. AB - The Western blotting (WB) method was used to evaluate the prevalence of human alveolar echinococcosis in Hokkaido, Japan. One hundred and sixteen WB-positive serum specimens were found in 1987 and 1988, and were grouped into two serologically different types from their WB-immunostaining patterns: "complete type", that showed multiple bands with various molecular weights ranging from 29 to 205 kilodaltons (kDa), and "incomplete type", that revealed a few bands with low molecular weights of 30-35 kDa and/or with molecular weights higher than 90 kDa. Therefore, we found that the WB method is applicable for the sero epidemiological studies of human alveolar echinococcosis in Hokkaido. PMID- 2255120 TI - An epidemic of echovirus 18 in 1988 in Japan--high association with clinical manifestation of exanthem. A report of the National Epidemiological Surveillance of Infectious Agents in Japan. AB - Laboratory reports of isolation of echovirus serotype 18 (E18) slightly increased in the summer of 1987 followed by a sharp increase with a peak in July, 1988. A total of 1,094 isolations were reported during these two years from 39 laboratories participating in the National Epidemiological Surveillance of Infectious Agents in Japan. When compared with the previous E18 outbreaks, a higher proportion of children at two years of age or under (58.3%) and a much higher incidence of exanthem (46.4%) were remarkable. Meningitis-associated isolations were reported in 30.6%, less than half of the percentage of the previous epidemic. PMID- 2255121 TI - Inhibition by beta-CCM of cholecystokinin-induced release of acetylcholine from the longitudinal muscle-myenteric plexus preparation in the guinea-pig ileum. AB - The antagonism between cholecystokinin (CCK) and methyl beta-carboline-3 carboxylate (beta-CCM) in the nervous system was studied by measuring the release of acetylcholine (ACh) from the longitudinal muscle-myenteric plexus preparation of guinea-pig. The ACh release was assessed by measuring [3H] output from the preparation preincubated with [3H] choline. Thirty mM of KCl caused a pronounced release of [3H] ACh from the preparation. Sulfated cholecystokinin octapeptide (CCK8) also increased the release of [3H] ACh in a dose-dependent manner at concentrations ranging from 10(-10)M to 10(-8)M. CCK8 at a concentration of 10( 8)M released [3H] ACh by about 300% of the 30 mM KCl-induced [3H] ACh release. In the presence of beta-CCM (10(-8)M to 10(-4)M), the release of [3H] ACh by KCl was not affected, but that by CCK8 was significantly inhibited depending on the concentrations of beta-CCM. These results show that the action of CCK8 to stimulate neurons in the myenteric plexus can be selectively antagonized by beta CCM. PMID- 2255122 TI - [Studies on function of the upper urinary tract. XXIX. Canine ureteral electromyogram isolated from "so-called Pacemaker"]. AB - Many workers have reported that ureteral peristaltic movement is controlled by the "so-called Pacemaker". But, in our recent studies, it was revealed that the existence of pacemaker is not always necessary for the peristaltic movement. In this study, we made isolated and non-isolated prototype models, using 18 mongrel dogs, to explore the influential factors on ureteral peristaltic discharge. Bilateral kidney and ureter were exposed transperitoneally. Unilateral upper urinary tract was prepared to preserve the pacemaker without renal blood supply, and contralateral one was prepared not to preserve the pacemaker by cutting at the proximal portion of the ureter. Vesico-ureteral reflux (VUR) was caused on these two models. A luminal pressure and ureteral electromyogram was recorded. In the result, there is spontaneous peristaltic discharges of the ureter which had the tendency to increase peristaltic frequency according to the increase of the luminal pressure. It was suggested that adequate expanding stimulation is the factor of peristaltic discharge to increase, and the peristaltic discharge under this condition propagates from upper to lower portion of the ureter. PMID- 2255123 TI - [The effects of various gastrokinetic drugs on gastric emptying]. AB - In order to elucidate the effects of various gastrokinetic drugs on gastric emptying and the sites of their action in the stomach, changes in gastric emptying after administration of these drugs were determined in healthy adults by means of radioisotopic technique, by setting 3 regions of interest, i.e., the whole stomach, the proximal area and the antral area. Following results were obtained. 1. With metoclopramide administration, no particular movement of gastric contents was found for several minutes after ingestion. Once the movement of emptying was initiated, the gastric contents were transferred more efficiently from the proximal area to the antral area in comparison with the corresponding movement observed in persons given no metoclopramide. On the other hand, the outflow from the antral area to the duodenum exceeded the inflow from the proximal area to the antral area. 2. With domperidon administration, transfer of gastric contents was markedly increased, but the outflow from the antral area did not exceed the inflow. Domperidone caused overall facilitation of gastric emptying, mainly by enhancing the emptying movement in the proximal area. 3. With aclatonium napadisilate administration, marked transfer of the gastric contents from the proximal area to the antral area was noted, and the outflow from the antral area to the duodenum was equal to the inflow within 10 min, then exceeded the inflow. 4. With trimebutine maleate administration, transfer of gastric contents from the proximal area to the antral area was conspicuous, and the outflow from the antral area exceeded the increased inflow, resulting in overall faciliation of gastric emptying. PMID- 2255124 TI - [Experimental investigations of the propagation mechanism and the nerve regulatory mechanism of the interdigestive migrating electric complex in intestinal movement]. AB - Segments and Thirty-Vella type loops of the small intestine of dogs were prepared, and the excitation propagation pattern of the interdigestive migrating electric complex (IMEC) was observed by electromyography. The nerve regulatory mechanism in intestinal movement was investigated. The results indicated that first, the frequency of the basic electric rhythm (BER) is controlled so that a downward gradient is formed from the upper to the lower intestine, but this gradient continues to be controlled by a two-dimensional control mechanism involving parietal factors and extrinsic nerves due to transection of the intestines and damage to the extrinsic nerves in the dominant region. However, propagation of the IMEC in the small intestine appeared to be regulated by a combination of the two-dimensional control mechanism involving extrinsic and parietal nerves corresponding to the BER control mechanism. It was clear that the propagation mechanism of IMEC is related to the BER frequency, and propagation of the IMEC is downward in accordance with the frequency gradient of BER. PMID- 2255125 TI - Control of brain microcirculation by endothelium. AB - Pial arterioles of mice are studied by in vivo TV microscopy. Focal endothelial injury is produced by a laser/Evans blue technique. Moderate damage results in local platelet aggregation. Very slight damage, without electron microscopic evidence of injury, results in loss of many endothelium derived vasoactive factors. These include "EDRFs" for acetylcholine, bradykinin and calcium ionophore, and "EDCFs" for histamine and serotonin. In the cases of acetylcholine, histamine and serotonin, each agonist possesses an additional opposing action which is independent of endothelium. The latter action is unmasked by the endothelial injury. The balance between simultaneously acting endothelium dependent and endothelium independent actions is a determinant of the response to an agonist with two opposing actions. This balance is partly dependent upon initial tone. Thus the effect of the agonist depends on initial tone. One of the determinants of initial tone may be basal release of one or more EDRFs or EDCFs. Evidence in pial arterioles for the basal release of EDRF for acetylcholine, comes from our data showing that L-NMMA constricts these arterioles. L-NMMA is a known inhibitor of synthesis of "classical" EDRF from L arginine. The response to L-ARG is relaxation. Both the response to L-NMMA and the response to L-ARG are abolished by laser/dye injury of the endothelium. Thus these agents are really acting via an endothelial mechanism in brain arterioles, just as has been reported for their actions in conductance vessels. Finally mild injury associated with loss of "EDRFs" is also accompanied by a reduced ability of pial arteriolar endothelium to repell activated platelets. PMID- 2255126 TI - Hallucinatory-delusional states in the elderly: treatment classification. AB - This paper describes a multi-dimensional study of non-organic hallucinatory states in the over-sixties. The subjects totalled 43 with no signs of obvious dementia or sustained confusion. Eleven biological, socio-psychological factors and 15 aspects of the clinical picture were assessed at the initial interview. Clinical symptoms were followed under medical treatment. Thirty eight subjects were followed for a further one year. One month later these subjects were classified into three groups. Group I, Complete Recovery Group (18 subjects). The characteristics of this group were: same sex ratio, good previous adaptation, high educational level, normal marital state, high rate of precipitating events, good response to treatment, acute onset, vividness and concreteness of the hallucination, fragmentariness of the delusion, high rate of anxiety and psychomotor excitement and good rapport. The course resembled "psychogenic reaction" and at the same time it resembled "organic brain syndrome" in symptoms. A possible interpretation is that under the influence of precipitating factors, "subclinical" cerebral hypofunction due to senility lapsed transiently into "apparent" cerebral hypofunction, leading to acute hallucinatory-delusional state. Group II, Partial Recovery Group (22 subjects). The characteristics of this group were: predominance of females, presence of precipitating events, fair response to treatment and subacute onset. This group was similar to Roth's "late paraphrenia" and Janzarik's Altersschizophrenie. Group III, Refractory Group (3 subjects). The characteristics of this group were: poor response to treatment and chronic onset. Two fell into dementia within one year. The symptoms of two subjects in the refractory group could be interpreted as prodromal symptoms of dementia. Aging reduces the redundancy of cerebral function to cope with the environmental changes. Among the elderly, events in daily life may often become precipitating factors of hallucinatory-delusional states. For the prophylaxis of hallucinatory-delusional states in elderly, serious attention should be paid to the psychological and somatic conditions which precede to these precipitating factors. PMID- 2255127 TI - Digital imaging system for recording rapid changes in intracellular Ca2+ concentrations triggered by electrical stimulation of cardiac myocytes. AB - To examine the origin and spreading of the Ca2+ transient following electrical stimulation of isolated myocyte, a system capable of recording intracellular Ca2+ distribution with sufficient temporal and spatial resolution was constructed. The system consists of a fluorescence microscope with computer-controlled pulse illumination and a digital image analyzer. The results with this new equipment show that the Ca2+ transient originates from one or a few points within a myocyte, and spreads throughout the cell. During the initial 60-msec period, the distribution of Ca2+ within a myocyte was not uniform. The system may be used for better understanding of the excitation-contraction coupling mechanism occurring within a cardiac myocyte or of changes in intracellular Ca2+ concentrations in other cells in which Ca2+ plays a crucial role in signal transduction. PMID- 2255128 TI - Assessment of growth hormone secretion in children. AB - Growth hormone (GH) is secreted in a pulsatile way during the whole life under the reciprocal influence of somatostatin and GH-releasing hormone (GHRH). It mediates many effects by stimulating production of insulin like growth factor I (IGF I) in liver and other tissues, but IGF I is also regulated by the nutritional state. Women secrete more GH than men, and older men and women less than young women. This suggests importance of estradiol in regulating secretion. Sex hormone effects are also demonstrated by the increment of GH and IGF I at puberty, which is an amplitude-modulated phenomenon. Classic metabolic studies have shown that patients with GH-deficiency retain more nitrogen in response to a given dose of exogenous hGH than normal subjects. The use of the stable isotope 15N has simplified such studies. In GH-deficient patients, there was with this technique a marked positive hGH-induced balance change. In girls with Turner syndrome (as example of subjects with normal GH-secretion), balance change was less marked with the same dose. Girls with Turner syndrome, who were given a double hGH-dose showed a response in the same range as that in the GH-deficient patients with the lower dose. A conclusion from this is that patients with normal GH-secretion need higher doses to obtain a similar response, than patients with GH-deficiency. The dosage in such patients will have to be selected individually, and needs to be about twice or three times as high as in GH-deficient patients. PMID- 2255129 TI - The diagnosis of nonanginal chest pain. AB - The term "atypical chest pain" is a waste-basket term that leads physicians to send any patient with chest pain to coronary angiography. In order to avoid this term, we must learn to distinguish atypical angina from nonanginal chest pain before angiography is considered in order to avoid unnecessary invasive procedures. A chest pain is very likely nonanginal if its duration is over 30 minutes or less than 5 seconds, it increases with inspiration, can be brought on with one movement of the trunk or arm, can be brought on by local fingers pressure, or bending forward, or it can be relieved immediately on lying down. There are also many presumptive signs of nonanginal chest pain such as localization with one finger, radiation to the nuchal area, an inframammary primary site, a pain that reaches maximum at the onset, or relief within a few seconds of swallowing food. Cervical root compression pain and esophageal spasm are the greatest mimics of angina since they can both be relieved by nitroglycerin but they have several features which help to rule out angina. PMID- 2255130 TI - A 77-year-old woman with proteinuria: saddle nose and disorders in the central nervous system. PMID- 2255131 TI - [State of lipid metabolism, platelet aggregation and microcirculation in patients with angina pectoris during plasmapheresis treatment]. AB - The paper presents the changes found in the lipid spectrum in 48, platelet aggregation in 23 and microcirculation in 35 patients with coronary heart disease after plasmapheresis. In patients with Functional Classes III and IV angina, repeated procedures of plasmapheresis were found to result in a clinical improvement of its course in 92% of the patients and in conversion to a lower functional class of angina in 71%. Massive plasmapheresis performed by the developed methods caused a significant improvement in the lipid spectrum, blood rheology, and microcirculation, which persisted for 1 to 6 months after plasmapheresis in relation to the type of hyperlipoproteinemia. PMID- 2255132 TI - [Lasers in surgery of arrhythmia]. PMID- 2255133 TI - [Characteristics of disorders of hemostasis and lipid metabolism in patients with different pathogenetic forms of angina pectoris]. AB - The likely mechanisms responsible for the occurrence of angina pectoris, which were revealed by 24-hour ECG monitoring, were correlated with abnormalities in hemostasis and blood lipid spectrum. Changes in the blood lipid spectrum were demonstrated to play the leading role in the development of angina due to higher myocardial oxygen demand. Those in platelet hemostasis are mostly pronounced in impaired myocardial oxygen supply due to vessel spasm and/or formation of platelet aggregates. PMID- 2255134 TI - [Effects of restoration of coronary circulation on the function of the left ventricle in patients with acute myocardial infarction (a follow-up after 1 year)]. AB - Values of overall and local left ventricular function were studied in 89 patients in the acute period and 1 year following myocardial infarction. Three patient groups were identified: (1) 26 patients with coronary artery patency recorded by the first coronary angiography; (2) 20 with coronary blood flow recovery made by thrombolytic therapy; and (3) 40 with coronary occlusion. There was a significant improvement of left ventricular function in the patients from Group 1 during their hospital treatment and 1 year after. PMID- 2255135 TI - [Mechanisms of the effects of physical training on the functional state of blood platelets in patients with ischemic heart disease]. AB - The platelet-vascular hemostasis and lipid peroxidation were examined in 60 male patients with coronary heart disease during their 30-day daily bicycle ergometric exercise performance. During the exercise, the patients were demonstrated to have a lower platelet aggregability. The factors that contribute to a physical training-induced decrease in the functional activity of platelets include lower levels of cholesterol, thrombin, lower blood oxidative activity and higher concentrations of prostaglandin I2 and high density lipoproteins. PMID- 2255136 TI - [Threshold oxygen consumption and anaerobic threshold in patients with ischemic heart disease and healthy subjects]. AB - Gas exchange and central hemodynamic parameters were examined in 70 patients with coronary heart disease and 40 healthy subjects during exercise. A low diagnostic informative value of threshold oxygen consumption values was found in the patients with coronary heart disease. It was shown that it was possible to indicate the anaerobic threshold in the patients by analysing the dynamics of cardiac output during exercise. PMID- 2255137 TI - [Significance of echo- and vectorcardiographic studies of the heart atrium in the assessment of intracardiac hemodynamics and myocardial contractility]. AB - Seventy three patients with coronary heart disease (CHD) complicated by paroxysmal atrial fibrillation (PAF) were examined. Vectorcardiography developed by I. A. Akulinichev and M-mode echocardiography were used to assess the status of left atrial and ventricular myocardia. An interrelationship was examined between the electrophysiological and echocardiographic parameters of myocardial performance, depending on the stage of circulatory insufficiency (CI). The patients with PAF-complicated CHD, unlike those with CHD alone, showed more severe myocardial conduction abnormalities despite the stage of CI. There were signs of compensatory left ventricular overload in the absence of clinical signs of CI. Comparison of ultrasound examination findings with high performance atrial vectorcardiographic ones increases the possibility of accurately assessing the cardiac performance by using noninvasive tools of examinations. PMID- 2255138 TI - [Effects of digoxin on ventricular arrhythmias in patients with mitral valve defects]. AB - A study was undertaken to examine 55 (27 females and 28 males) patients aged 25 to 74 years who had ventricular arrhythmias. Twenty five patients were diagnosed as having mitral valvular disease concurrent with predominant stenosis, 30 presented with prevalent mitral dysfunction. Twenty eight patients showed Stages I to IIA circulatory failure, and 27 had Stages IIB to III heart failure. All the patients displayed perpetual ciliary arrhythmia of various duration. More frequent and severe ventricular arrhythmias were recorded in mitral valvular disease patients with predominant mitral dysfunction than in those with stenoses. When the plasma digoxin concentration was less than 1.1 ng/ml in patients with a low end-diastolic volume and initial signs of circulatory failure, the agent produced an antiarrhythmic effects on ventricular arrhythmias in many cases, in mitral valvular disease patients with predominant stenosis in particular. The arrhythmogenic effect of digoxin was found in 47.6% patients with prevalent mitral dysfunction concurrent with Stages IIB-III circulatory failure. The agent may show arrhythmogenic action in mitral valvular disease patients with prevalent mitral dysfunction who had larger cardiac volumes and plasma digoxin concentrations of no more than 1.6 ng/ml in the absence of clinical signs of digitalis intoxication. PMID- 2255139 TI - [Clinico-physiological assessment of the mechanisms of compensation and paracompensation in patients with mitral stenosis]. AB - The paper presents the results of an examination of 292 patients with Stages II-V mitral stenosis. Clinical, roentgenological, and electrocardiographic characteristics of the defect were analysed. Physical fitness and gas exchange during exercise were studied in 183 patients with Stages III and IV mitral stenosis. The findings were compared with the intensity of tissue oxygen exchange and the levels of myocardial myoglobin. The patients with mitral stenosis exhibited lower exercise tolerance that was more pronounced in Stage IV. The patients also displayed characteristic profound disturbances in work energy regimen, lower reserve potentialities and functional mobility of the cardiorespiratory system. The pronounced changes in the acid-base balance and gas composition of their capillary blood in Stage IV mitral stenosis during exercise may be explained by a sharply marked arteriolar barrier in the pulmonary circulation (a paracompensatory reaction). The comparison of physiological and clinical findings has enabled the relationship of mechanisms responsible for compensation and paracompensation to be evaluated at various stages of mitral stenosis. PMID- 2255140 TI - [Functional assessment of the state of patients after Fontan's operation]. AB - A bicycle ergometric test was performed in 27 patients 2.5 months to 5 years after Fontana's operation in order to study their physical working capacity and major parameters for cardiac pump and contractile functions by tetrapolar chest rheography and those for external respiration. In the early periods following the surgery, the patients showed a low physical working capacity with a respective reduction in the pump and contractile functions of the heart. In the late periods, in addition to positive clinical dynamics, there was an improvement of functional parameters for the cardiorespiratory system. The status in the majority of patients was steady-state for more than 2 years after the surgery. PMID- 2255141 TI - [Hemodynamic regularities of echocardiogram changes in congenital heart defects]. AB - Echocardiographic findings and catheterization outcomes were compared in 191 patients with congenital heart disease. There was a regularity of changes in echocardiographic parameters depending on the nature of hemodynamic loading. Indirect ultrasound signs were revealed, which determined the severity of various intracardiac hemodynamic manifestations and latent heart failure. PMID- 2255142 TI - [Atherosclerosis: treatment of hereditary hypercholesterolemia]. PMID- 2255143 TI - [Role of initial immunologic status of patients with congenital heart defects in the development of postoperative infectious complications]. AB - Before surgical correction of the defect, the immune status was examined in 65 patients with congenital heart disease who developed postoperative infectious complications. The patients showed significant changes in peripheral blood levels of various lymphocyte populations (E-, EAC-ROC) and immunoglobulins M, G, A. It was concluded that the occurrence of infections complications was related to the initial immunological status of patients with congenital heart disease. PMID- 2255144 TI - [Experience in the surgical treatment of combined atherosclerotic lesions of the coronary arteries, abdominal aorta and arteries of the lower limbs]. AB - A comprehensive clinicoangiographic and functional examination was made of 180 patients with combined coronary and vascular abnormalities. With this, a diagnostic algorithm was developed, which determined the authors' approach to evaluation of the severity of patients and the choice of surgical policy. A total of 150 patients were operated on, the total mortality being 7.3%. The examination of operative and hospital mortality rates in patients with combined abnormalities showed that pre-aortocoronary bypass surgery before a reconstructive vascular operation in patients with severe coronary diseases made it possible to avoid serious coronary events in the following postoperative period. PMID- 2255145 TI - [Studies of the motion of the anterior heart wall and central arteries using radiokinetocardiography]. AB - A total of 21 subjects without signs of circulatory abnormalities were examined by a noninvasive intrascopic cineradiocardiographic technique which involved recording of an electromagnet superhigh-frequency signal reflected from the heart and central arteries. The oscillations occurred in the initial segment of an echo signal were explored. Cineradiocardiography was demonstrated to allow the motions of the arterial wall of the ventricles, atria, and a proximal portion of central arteries to be studied. The areas for applying an aerial to the front chest wall were defined to record the motions of anterior heart walls and central arteries. The features of appropriate cineradiocardiograms were described. PMID- 2255146 TI - [Exercise tolerance in patients with exertion angina pectoris after therapeutic plasmapheresis]. AB - The bicycle ergometric test was used to examine exercise tolerance in 73 patients with coronary heart disease following a single remedial plasmapheresis session, which removed an average of 1562.2 ml plasma. A rapid increase in exercise tolerance was significantly revealed in patients with Functional Class IV exertional angina. PMID- 2255147 TI - [Assessment of the diagnostic significance of R wave amplitude changes in patients with ischemic heart disease in computer-assisted monitoring analysis of ECG during treadmill test]. AB - During treadmill exercise, 57 patients with documented coronary heart disease (CHD) were studied for the change patterns in R wave amplitudes in V5 lead by analyzing ECG on a computer. With exercise, 86% of CHD patients showed higher or no R wave amplitude changes, whereas 73.7% of healthy subjects displayed its lower changes. Increased or no R wave amplitude changes in CHD patients was accompanied by more marked quantitative ischemic parameters than their decrease. A significant correlation was found between higher R wave amplitude and extended exercise-induced myocardial ischemia. Decreased R wave amplitude was associated with local ischemic shifts. Comparison of the data obtained from the computer assisted ECG analysis and radiocardiometric findings during the exercise test demonstrated that an increase m R wave amplitude in CHD patients was followed by higher cardiac volume, which indicated ischemic myocardial dysfunction. PMID- 2255148 TI - [Anti-arrhythmic effect of adaptative activation of the vagus nerve system and a new synthetic acetylcholine analog]. AB - A higher vagal tone or its stimulation under certain conditions is known to increase the threshold of cardiac fibrillation and even to arrest developing arrhythmias. This effect is usually evaluated as a result of limiting the excessive adrenergic effect on the heart, which is observed in stress and ischemia. The following two facts have been first identified: 1) adaptation to moderate continuous stress may induce tonic excitation of parasympathetic regulation of the heart and enhance its resistance to ischemic and reperfusion arrhythmias; 2) this antiarrhythmic effect is completely reproducible by the recently synthesized acetylcholine analogue EDIHYP, ethyl-3/2-ethyl-2,2 dimethylhydrazinium/propionate iodate. PMID- 2255149 TI - [Immediate and long-term results of the use of plasmapheresis in obliterating atherosclerosis of the vessels of the lower limbs]. AB - Plasmapheresis was applied to treat 67 patients with lower extremity vessel atherosclerosis obliterans. A total of 92 therapy courses were performed, which involved 250 sessions of plasmapheresis (205 with a PF-0.5 apparatus and 45 with plastic bags and centrifuge). During the course, an average of 160% volume of circulating plasma were removed to be replaced with crystalloids and dextrans. A positive effect shown by a 6.9-fold increase in the distance covered by patients who experienced no pains and by resting pain relief was achieved in 93.8% with Stage II circulatory failure and 75% with Stage III, regardless of the severity of vascular lesions. It was shown that it was necessary to make a "programmed" plasmapheresis when the patient received 2 plasmapheresis courses a year. The mechanism of a positive effect of plasmapheresis remains unclear. A significant plasmapheresis-induced decrease was observed in the concentration of "acute phase proteins" (plasma fibrinogen and globulins), which plays the leading role in improving blood rheology, which seems to affect clinical outcomes. PMID- 2255150 TI - [Antiarrhythmic activity of ajmaline obtained from Rauwolfia serpentina biomass grown in tissue culture]. AB - The conventional experimental techniques showed that ajmaline derived from Rouwolfia serpentina Benth. biomass grown in tissue culture was effective in arresting canine ventricular arrhythmias induced by coronary occlusion, strophanthin and epinephrine, displaying antiarrhythmic effects in aconitine induced intoxication of rats and substantially elevating the threshold of ventricular fibrillations in cats. The antiarrhythmic activity of ajmaline produced by the biotechnological technique was identical to that of ajmaline derived from the natural root of Rauwolfia serpentina Benth, which allows one to recommend that the agent in question should be clinically tested as an antiarrhythmic. PMID- 2255151 TI - [Effects of low doses of activated protein C in experimental arterial thrombosis in rats]. AB - Activated C protein (ACP) is a physiological anticoagulant enzyme that is capable to inactivate factors Va and VIIIa, thereby having a wide spectrum of antithrombotic effects. Low-dose ACP was tested for its ability to affect anodic current-induced arterial thrombosis in the rat. ACP given in low doses (15 micrograms/kg, 7% of total C protein in the rat) was found to produce a marked antithrombotic effect. With this, the activated partial thromboplastin time remained virtually unchanged, and its antithrombotic action was equal to that of heparin administered in a dose of 125 U/kg. In the authors' opinion, ACP may form the basis for designing a highly effective antithrombotic agent. PMID- 2255152 TI - [Experimental and clinical study of Vasosan P, a new form of pectin-enriched cholestyramine]. AB - The bile acid sequestering agent Vasosan P is a new form of pectin-enriched cholestyramine (20%), saccharose (5%) and sorbic acid (0.18%). In comparison with cholestyramine Vasosan P has a more marked hypolipidemic effect in experiment. Vasosan P is remarkable for good organoleptic properties. It is effective in treating patients with type IIa hyperlipoproteinemia and practically has no side effects as cholestyramine. PMID- 2255153 TI - [Rate and acceleration of left and right ventricular myocardial motions in some congenital heart defects (data of ultrasound doppler echotachocardiography)]. PMID- 2255154 TI - [The notched anacrotic phenomenon in sphygmograms]. PMID- 2255155 TI - [Use of prazosin in the treatment of patients with hypertension]. PMID- 2255156 TI - [Measurement units of oxygen consumption in spiroergometric studies of heart surgery patients]. PMID- 2255157 TI - [Ectopic pacemaker in the left atrium: diagnosis and surgical treatment]. PMID- 2255158 TI - [A case of paroxysmal tachycardia caused by the presence of abnormal ventricular node tract]. PMID- 2255159 TI - [Myocardial revascularization using left internal thoracic and right gastro omental arteries and autologous venous shunt]. PMID- 2255160 TI - [Tear film diagnosis in contact lens wearers]. AB - Contact lenses have an intimate relationship with the precorneal tear film and it is important to attempt to prognosticate the likelihood of successful contact lens wear by evaluating, both quantitative and qualitative aspects of the precorneal tear film. Aspects of history diagnostic methods and general aspects which are necessary to notice prior to contact lens fitting are described in this review. PMID- 2255161 TI - [A tear strip test in the control of contact lens wearers]. AB - A series of 86 contact lens wearers has been examined by tear-stix tests (35 wearing hard lenses and 51 soft). Of these, 52 showed no infection (group A), while 34 had signs and/or symptoms of infection (group B). Leucocyte-esterase positivity was seen in 8% of group A and 62% of group B. Stix-positive were 13% of group A and 85% of group B (positive leucocyte-esterase and/or positive nitrite and/or positive hemoglobin). The examinations are quick and easy to carry out, with a reasonable sensitivity and specificity. PMID- 2255162 TI - [Importance of diagnosis and preoperative care of the conjunctiva]. AB - The conjunctival smear is an important part of preoperative diagnosis. Although the method is very easy there are many possible sources of error. The validity of smear results was studied; the sources of error are discussed in the present paper. The different bacterial flora of the conjunctival sac and the lid margin were investigated. It was shown that eye drop dispensers become contaminated during use. The use of single-dose Ophtiolen has the advantage--in addition to improved hygiene, that no stabilizing agents are used. Preoperative efforts to achieve asepsis have to be continued during the operation. A new adhesive tape specially developed for ophthalmic surgery has been found very effective. This new tape is described. PMID- 2255163 TI - [Significance of raised intraocular pressure in glaucomatous visual field defects. A clinical study]. AB - 1. 300 eyes of 300 patients with primary open angle glaucoma (POAG) were examined with program 31 of the Octopus perimeter 201 and the amount of visual field loss (total loss) was quantified with program Delta. The total loss was correlated to the height of the maximum intraocular pressure (IOP max). There was no correlation in the interindividual comparison between IOP max and total loss. This shows the influence of IOP independent risk factors in POAG. 2. In an intraindividual comparison 108 eyes of 54 patients with POAG were examined under the question: Have eyes with the four times higher amount of visual field loss in one eye compared to the other, a significant higher IOP max in the eye with the more severe damage. The intraindividual comparison excludes cardiovascular risk factors, because they affect both eyes. So the difference in IOP can show better the damaging influence of IOP: Eyes with the higher amount of visual field loss showed a significant higher IOP max. This shows the impact of the elevated IOP is a risk factor in POAG. 3. 300 eyes of 300 patients with POAG were further examined under the question, whether the relation between the mean loss per test point in the upper half of the visual field in comparison to the mean loss per test point in the lower half of the visual field is different at different IOP max levels. 162 eyes with an IOP max of less than 30 mmHg and 75 eyes with an IOP max of 30 up to 36 mmHg and 63 eyes with IOP max of 37 and more mmHg were evaluated and the 3 groups were compared. With an increasing height of IOP max an increasing equal distribution of the visual field loss in upper and lower visual field half was found. High IOP results in a diffuse nerve fibre damage and more IOP-unindependent risk factors result in localized visual field damage. So there are at least two pathomechanisms in POAG. PMID- 2255164 TI - [Examinations by ocular pressure tonometry]. AB - A new method has recently been suggested for the determination of the outflow resistance in the anterior chamber angle. In this method the intraocular pressure is set to 45 mmHg for 8 minutes. The intraocular pressure is measured after the removal of the suction cup. Values below 7 mmHg are obtained in healthy subjects. Values above 7 mmHg are thought to be indicative for glaucoma. By setting the intraocular pressure to 45 mmHg for the expression of fluid the authors claim to have brought normalization to tonography. We show here in a series of results that we can reproduce the results which have been published by Ulrich et al. For normalization of a tonographic test we need a pressure rise which effects a uniform expression of volume. According to the knowledge presently generally agreed upon a uniform expression of volume is obtained by increasing the intraocular pressure by a constant factor and not by increasing it to a constant level. In 30 healthy volunteers and in 30 glaucoma patients we have increased the intraocular pressure by the constant factor of 1.8. According to our results the glaucoma patients and the healthy subjects can no longer be differentiated. A better differentiation is possible by the initial intraocular pressure. Thus we have shown that the favorable results by ocular pressure tonometry are mainly due to the intraocular pressure before the test. We feel therefore that ocular pressure tonometry should not be incorporated in our diagnostic armamentarium for glaucoma diagnosis. PMID- 2255165 TI - [The expanding gas operation after a 15-year use. Animal experiment studies, subsequent developments of the method and clinical results in the treatment of ablatio retinae]. AB - The expanding-gas-operation, a detachment surgery consisting in an intraocular (i.o.) injection of an expanding gas such as SF6 (without drainage and without vitrectomy) in combination with cryo or laser, was described by Kreissig in 1979. The method was used in the treatment of tears problematic for tamponading by extraocular (e.o.) plombages (giant tear, hole in posterior pole, scattered groups of breaks). With the introduction of the perfluorocarbon gases (CF4, C2F6, C3F8, C4F10) by Lincoff and his group in the beginning of the eighties the use of the gas-operation was improved: the expansion of the new gases ranged from 1.9x to 5x and their i.o. duration, defined as half time volume, from 6 to 45 days. However, animal experiments confirmed that an expanding i.o. gas bubble induces a break-down of the blood aqueous barrier, an increase of protein, an infiltration of cells into the vitreous and a compression of vitreous membranes against the retina implying the threat of subsequent proliferative vitreoretinopathy (PVR). The expanding-gas-operation is contraindicated in a detachment with PVR stage C and D. In spite of a recent renaissance of the expanding-gas-operation by Dominguez and Hilton in the middle of the eighties, the issue is still valid: in the treatment of a detachment an e.o. plombage is better than an i.o. gas bubble; this is especially pertinent for uncomplicated retinal detachments representing the indication of choice for a temporary e.o. plombage without drainage, the balloon-operation. As a consequence, at present the expanding-gas-operation is only justified for problematic retinal tears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255166 TI - [Measurements of corneal thickness in patients with keratoconjunctivitis sicca]. AB - The average corneal thickness in a group of patients with KCS did not differ significantly from that in a control group. Within the patient group the corneal thickness decreased with decreasing lysozyme concentrations and also with decreasing Schirmer values, but the correlation was weak in both cases. The average central corneal thickness with severe and very severe KCS was greater than that of patients with mild KCS and the control groups. The average corneal thickness in patients with mild KCS was less than that of the control group, but not significantly so. Because of the comparatively small number of patients with severe KCS, an all over increase in corneal thickness in patients with KCS could not be demonstrated. PMID- 2255167 TI - [Examinations of the cornea and anterior chamber angle region with a laser tomographic scanner (LTS)]. AB - The Laser Tomographic Scanner LTS based on laser scanning and confocal detection is a system to generate and measure optical section images. The periphery of the cornea and the anterior chamber angle region is shown in the horizontal section image with high image quality and high signal-to-noise ratio. 130 patients and 163 eyes were examined in this way. First experience shows possible applications for special clinical situations. Using horizontal optical section images, a procedure is generated to measure the anterior chamber angle without contact or local anesthesia with a reproducibility of 2 degrees. Horizontal section images clearly demonstrate changes of anterior chamber angle depth following e.c. cataract extraction and implantation of posterior chamber IOLs. Using the generated measurement procedure, these changes could be quantified. PMID- 2255168 TI - [Ablation of the trabecular meshwork]. AB - In an experimental investigation we examined the possibility to create an open pathway between the anterior chamber and Schlemm's canal by excimer laser ablation of the trabecualr meshwork (AT) in enucleated eyes. A quartzfiber was directed through the anterior chamber to the opposite chamber angle. With an energy of 0.3-1.5 mJ and wavelengths of 248 and 308 nm pores were easily made into the trabecular meshwork leading to a direct connection between the anterior chamber and Schlemm's canal. This result was confirmed by histologic examination of the globes. The trabecular meshwork has disappeared completely. The surrounding tissue reveals only minimal thermal effects due to the laser burns. With the same method cyclodialysis and basal iridectomy may be performed. The operation is simple and effects can be placed with great accuracy. PMID- 2255169 TI - [A new topical carbonic anhydrase inhibitor (MK-927). Tolerance comparison with betaxolol in healthy probands]. AB - MK-927 is a new topical carboanhydrase inhibitor with proven ability to lower intraocular pressure in glaucoma patients. Subjective and objective symptoms following topical application of MK-927 were evaluated in a randomized, double blind, placebo-controlled study in which 24 healthy male volunteers took part. Symptoms were rated according to a visual analog scale by the volunteers and according to a grading scale by the examiner. The study showed good local tolerance of MK-927, comparable to that of Betaxolol. PMID- 2255171 TI - [Is endothelial microscopy necessary before cataract surgery?]. AB - Specular microscopy was performed before cataract surgery in approximately 3,500 patients. In 127 cases (approx. 4%), implantation of an intraocular lens (IOL) did not appear appropriate, in view of the condition of the cornea. Many of these patients had additional ocular pathology, such as retinal detachment, glaucoma, and intraocular inflammation. In 40 of the patients, IOLs were implanted in spite of the results of specular microscopy, while 48 patients underwent surgery without lens implantation. The incidence of postoperative corneal complications in the two groups was the same. The main problems were caused by cell polymorphism and severe cornea guttata. It is extremely difficult to assess cell polymorphism at the slitlamp. Especially in patients with other ocular diseases and corneal lesions visible at the slitlamp, it is recommended that specular microscopy be performed prior to cataract surgery with implantation of an IOL. PMID- 2255170 TI - [Ocular changes in MELAS syndrome]. AB - The present paper reports on the clinical findings of a 34-year-old male patient with MELAS syndrome. MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes) belongs to a group of syndromes called mitochondrial encephalomyopathies that are characterized by changes of the mitochondrial respiratory chain and the histological finding of "ragged red fibers" in muscle biopsy. In our case the diagnosis was confirmed by multiple neurologic tests including muscle biopsy and biochemical analysis of the respiratory chain. The ocular findings included reversible, homonymous hemianopic visual field loss documented six years earlier, atypical retinitis pigmentosa with marked attenuation of the scotopic ERG, myopia and nuclear cataract of the right eye. An extracapsular cataract extraction with implantation of a posterior chamber lens was performed on the rigt eye, the course was unremarkable and vision improved. In dealing with patients presenting with ocular or neurologic signs indicating mitochondrial encephalopathy, the ophthalmologist should consider MELAS syndrome or any other of the mitochondrial encephalomyopathy syndromes as a possible etiology and take the necessary steps for further medical and neurologic evaluation of the patient. PMID- 2255172 TI - A case of ornithine transcarbamylase deficiency with acute and late onset simulating Reye's syndrome in an adult male. AB - A 15-year-old male was admitted to the hospital because of a disturbance of consciousness. He was in good mental and physical condition until the previous day, when he vomited and experienced a reduction of consciousness. He was brought to the hospital the day following the onset of symptoms. On admission the patient was stuporous. Neurological focal signs were not demonstrated. Computed tomographic (CT) scanning on admission showed no definite abnormality. Cerebrosprinal fluid had no pleocytosis. At this time, Reye's syndrome was suspected because of the acute change of consciousness and the presence of hyperammonemia. The disturbance of consciousness progressed and he became comatose on the day following admission. CT scanning showed that the suprasellar, ambient and quadrigeminal cisterns could almost not be detected and the bilateral ventricles were narrowed. The plasma aminogram demonstrated an elevation of alanine, lysine, glutamine, glutamic acid, aspartate and proline. Ketonuria was negative, but the urinary excretion of orotic acid was markedly increased. This data was indicative of the existence of an ornithine transcarbamylase (OTC) deficiency. The patient was died on the third day after hospitalization. The OTC activity in the liver was 10% of normal. Activities of other enzymes in the urea cycle were within normal limits. It is unusual that the symptoms of the enzyme deficiency occurred, both acutely and late at an adult age, as in this case. This case demonstrates that OTC deficiency should be considered in the differential diagnosis of hyperammonemia of adult onset. PMID- 2255173 TI - Alterations in gap junctions of human endometrial epithelial cells during normal menstrual cycle--freeze-fracture electron microscopic study. AB - Gap junctions between human endometrial epithelial cells were studied at various phases of the normal menstrual cycle by freeze-fracture electron microscopy. The junctions changed in number and size according to the phases of the menstrual cycle. Only small and few gap junctions were found in the early proliferative phase. In the early secretory phase the junctions were larger and found more often in the earlier phase. In the late secretory phase the junctions were much smaller than in the early secretory phase. The cyclical changes of the junctions may have a role in controlling the proliferation and differentiation of the endometrial epithelium. PMID- 2255174 TI - Forskolin actions on transient potassium current of rat ventricular cardiomyocytes. PMID- 2255175 TI - Whole cell recordings from acutely dissociated septal neurons. PMID- 2255176 TI - Effects of stress, non-stress cyclicity on hypothalamic noradrenaline release in rats. AB - The effects of continuous stress and intermittent stress at short intervals on rat hypothalamic noradrenaline (NA) release were assessed by measuring the levels of a principal metabolite of NA, 3-methoxy-4-hydroxy-phenylethyleneglycol sulfate (MHPG-SO4) in male Wistar rats. The rats were exposed to one of five restraint stress conditions, unstressed (control), six 15 min intermittent stress periods (interspersed with 18 min non-stress periods), three 30 min intermittent stress periods (interspersed with 45 min non-stress periods), 90 min continuous stress period or 180 min continuous stress period. The 15 min intermittently stressed rats had significantly larger increases in hypothalamic MHPG-SO4 than the single 90 min and 180 min continuously stressed rats, while the 30 min intermittently stressed rats were significantly different from only the 180 min continuously stressed rats. In a comparison of the 15 min and 30 min intermittently stressed rats, which had the same total duration of stress exposure; the 15 min group had larger increases in MHPG-SO4 levels than the 30 min group. This study provides supporting evidence for the role of stress cyclicity in determining the extent of stress-induced NA release from the hypothalamus. PMID- 2255177 TI - Histopathological studies on the cystic formation of the human urothelium. AB - Histopathological examination of pyeloureteritis cystica and cystitis cystica revealed the mechanisms for the cystic formation of the urothelium. Chronic stimulation with inflammation or physical stimulation with crystals or calculi causes the urothelium to form an inflammatory crypt. The crypt is isolated as a result of an adhesive occlusion of the urothelium at the orifice of the crypt. This crypt is an immature cyst that cannot be clinically detected. A von Brunn's cell nest represents a cut surface of the immature cyst. The inflammatory cyst isolated from the urinary tract, i.e., the immature cyst, gradually grows into a complete cyst, i.e., a clinically visible mature cyst, because of a hydrodynamic flow between the surrounding tissue and neogenetic capillaries, and inflammation. These findings indicate that von Brunn's cell nest, and glandular and cystic formation, occur during development from an inflammatory crypt to an immature cyst and then, a mature cyst. PMID- 2255178 TI - The vitamin A-storing cells in the human and rat pancreas. AB - Vitamin A-storing cells with lipid droplets and fluorescence characteristic of vitamin A were observed in the normal human and rat pancreas, using light, fluorescence, and electron microscopy. Vitamin A-storing cells in the normal human pancreas, as well as in the rat pancreas, were located predominantly in a perivascular area, and had lipid droplets with a fluorescence characteristic of vitamin A, Pancreatic vitamin A-storing cells had more numerous jipid droplets and more distinct fluorescence of vitamin A in vitamin A-loaded rats than in normal rats. In the rat, hepatic vitamin A-storing cells contained significantly more lipid droplets and had more distinct vitamin A fluorescence than pancreatic vitamin A-storing cells. Pancreatic sections from human subjects with chronic alcoholic pancreatitis revealed abundant vitamin A-storing cells surrounded by collagen fibers in an area of fibrosis. These results indicate that vitamin A storing cells are widely distributed in the normal human and rat pancreas, although pancreatic vitamin A-storing cells have less storage capacity for vitamin A than do hepatic cells. Vitamin A-storing cells, as well as fibroblasts, may participate in the development of pancreatic fibrosis in chronic alcoholic pancreatitis, similar to the way hepatic vitamin A-storing cells participate in hepatic fibrosis. PMID- 2255179 TI - Acute-phase kidney transplants show early peak appearance in Tc-99m DTPA renogram. AB - Kidney transplants have been evaluated using a radionuclide technique to determine perfusion index (PI), mean transit time (MTT), and the parameters in renogram curve (Tmax, T1/2, and T2/3). The values for Tmax, T1/2, and T2/3 were also determined in normal volunteers. The results indicated that the Tmax value was less than 2 minutes, one week after transplantation. The other data were within normal limits. The appearance of Tmax was very early. The early time activity curve (TAC) was quite similar to the blood disappearance curve, TAC did not have the functional-phase, so-called, 2nd-phase. These data suggested that there could be an abnormality of the renal circulation in the transplanted kidney. The suggestion offers the new finding in a field of renal transplantation using radionuclide technique. PMID- 2255180 TI - Gallium-67 citrate uptake in experimental tumors and inflammatory lesions--an histo-autoradiographic correlation. AB - In a DAB-hepatoma organic tumor, Ga-67 accumulated markedly in the hepatocellular carcinoma with scant stroma but not in the cholangioma that was rich in connective tissue. No granulation tissue was formed around the tumor. In transplanted tumors (Ehrlich's tumor and Sarcoma 180), Ga-67 accumulated in the granulation tissue within the fibroblasts, leukocytes and capillaries surrounding the tumor, rather than in the tumor. In inflammatory lesions, Ga-67 uptake was similar in granulation tissue with large numbers of phagocytes, such as leukocytes and histiocytes, and capillaries. There was a very good correlation between the degree of Ga-67 uptake and of cellular infiltration and the proliferation of capillaries. Ga-67 uptake, both in inflammatory lesions and in transplanted tumors, was observed in the granulation tissue. This result implies that the mechanisms of Ga-67 uptake in tumor and inflammatory tissues are not the same, because Ga-67 accumulated in the DAB-hepatoma that had no inflammatory granulation tissue. This study indicates that a non-transplanted tumor is required to study Ga-67 accumulation in tumors, as different results may occur in tumors with and without inflammatory granulation tissue. PMID- 2255181 TI - Bacterial endotoxins and the liver. PMID- 2255182 TI - Acute administration of ethanol to rabbits inhibits thrombus formation induced by indwelling aortic catheters. AB - Platelet aggregation and secretion of granule contents in response to specific agonists are inhibited by acute ethanol (1 to 4 mg/ml in vitro or 4 to 5 mg/ml ex vivo). However, acute administration of ethanol, giving blood levels of 4 to 5 mg/ml, does not affect platelet adherence to de-endothelialized rabbit aortae in vivo, which is the initial step in thrombus formation. Whether ethanol inhibits subsequent reactions in thrombus formation induced by indwelling catheters in rabbit aortae was investigated. Before insertion of the catheters, the rabbits received injections of 51Cr-labeled platelets (and, in some experiments, [125I]fibrinogen), and were given ethanol by stomach tube, to achieve blood levels of approximately 4 mg/ml. Thrombus formation after 3 hours was assessed by determining the number of platelets and the amount of radiolabeled fibrin(ogen) associated with the aortae, and by determining the thrombus weights; all three measurements indicated a 64 to 84% reduction in thrombosis. Thus, experimentally induced thrombus formation in the aorta is significantly reduced by ethanol. PMID- 2255183 TI - Intrapulmonary tumor necrosis factor triggers local platelet-activating factor production in rat immune complex alveolitis. AB - Recent studies suggest that intrapulmonary tumor necrosis factor (TNF) participates in the pathogenesis of acute IgG immune complex alveolitis through a mechanism involving neutrophil polymorphonuclear leukocyte (PMN) recruitment. There are few in vivo studies that address mechanisms of TNF-dependent PMN recruitment and tissue injury. We have examined the relationship between intrapulmonary TNF and locally generated platelet-activating factor (PAF) in the development of acute alveolitis. Intratracheal instillation of IgG anti-bovine serum albumin followed by intravenous bovine serum albumin results in acute neutrophil-mediated alveolitis. Induction of IgG immune complex lung injury resulted in a marked increase in the whole lung and bronchoalveolar lavage PAF levels. Intratracheal instillation of the PAF antagonists, L-652,731 (Merck, Sharpe, and Dohme, Rahway, New Jersey) or WEB-2086 (Boehringer), attenuated pulmonary vascular leakage and PMN recruitment into the alveolar compartment. Neutralization of intrapulmonary TNF with anti-TNF antibodies reduced pulmonary vascular permeability, PMN recruitment, and whole lung PAF levels. Incubation of isolated mouse alveolar macrophages with recombinant murine TNF resulted in rapid (30 to 60 minutes), cell concentration-dependent PAF release. The presence of high concentrations of PAF in whole lungs obtained from PMN-depleted rats after immune complex deposition suggest that recruited PMN are not the predominant source of intrapulmonary PAF in this model. These data suggest that acute IgG immune complex alveolitis is in part mediated by TNF-triggered PAF production and that locally produced PAF promotes recruitment of PMN into the alveolar compartment. PMID- 2255184 TI - Glomerular localization of platelet cationic proteins after immune complex induced platelet activation. AB - Synthetic polycations bind to glomerular polyanions (GPA) and increase permeability to macromolecules and immune complexes. Platelet factor 4 and other platelet cationic proteins also bind to GPA and may play a role in immune complex deposition. Here we examine the potential of locally released cationic proteins to bind to GPA after immune complex-induced platelet activation within the renal microvasculature. Rabbits were immunized against bovine serum albumin (BSA), and BSA (2 or 4 mg/ml in buffered saline) was infused into the left renal artery to deliver 8 or 16 mg of BSA over 20 minutes. Thirty minutes later, kidneys were removed and tissue processed for light, immunofluorescence, and electron microscopy for the assessment of glomerular alterations and the localization of immune complexes (IgG and BSA), platelet factor 4, and platelet cationic proteins. GPA was measured by quantitative ultrastructural assessment of polyethyleneimine binding sites. Glomerular capillaries contained large intraluminal immune complexes and platelet aggregates. Also, numerous deposits were observed within subendothelial and subepithelial aspects of the glomerular basement membrane (GBM). Immunofluorescence and immunocytochemistry revealed prominent localization of platelet factor 4, platelet cationic proteins, IgG and BSA within peripheral capillary walls of glomeruli concomitant with a reduction in GPA. Glomeruli of controls or contralateral kidneys did not show GBM localization of immune complexes or platelet proteins. Thus, nascent formation of immune complexes in capillaries was associated with platelet activation and deposition of endogenous cationic proteins in the GBM. This mechanism may be involved in neutralization of GPA and mediation of increased permeability, which leads to GBM deposition of immune complexes. PMID- 2255185 TI - Analysis of alpha 1 (I) procollagen alpha 1 (IV) collagen, and beta-actin mRNA in glomerulus and cortex of rabbits with experimental anti-glomerular basement membrane disease. Evidence for early extraglomerular collagen biosynthesis. AB - Renal cortical and glomerular mRNA for alpha 1 (I) and alpha 1 (IV) collagen were measured by filter hybridization during experimental anti-glomerular basement membrane disease in the rabbit. The abundance of alpha 1 (IV) mRNA was 5 times greater in total RNA isolated from glomeruli as compared with whole renal cortex from normal rabbits. In contrast, there was no difference in the relative amounts of alpha 1 (I) procollagen mRNA in these two fractions. Four days after the administration of anti-glomerular basement membrane antisera, a time histologically characterized by glomerular inflammatory cell infiltration without crescent formation, beta-actin mRNA were increased 17-fold in glomeruli and 4 fold in whole renal cortex. Renal cortical mRNA for alpha 1 (I) and alpha 1 (IV) were increased 7-fold (p = 0.07) and 9-fold (p less than 0.05), respectively compared with normal rabbit kidney cortex. In contrast, there was no significant difference in the abundance of these mRNA in glomeruli at day 4. By day 7, cortical alpha 1 (I) and alpha 1 (IVP mRNA had increased 17- and 10-fold, respectively, and these transcripts had increased 13- and 7-fold in glomeruli. Cortical alpha 1 (I) mRNA remained elevated for 35 days. These data show that large changes in collagen mRNA levels occur early in this model of crescentic nephritis in the rabbit, and that extraglomerular collagen mRNA accumulates very rapidly when glomerular inflammation occurs. Extraglomerular collagen synthesis associated with intraglomerular inflammation may help to explain the common association of interstitial fibrosis with glomerulonephritis, particularly in the periglomerular area. PMID- 2255186 TI - Cellular events in experimental unilateral ischemic renal atrophy and in regeneration after contralateral nephrectomy. AB - Two related morphological studies were undertaken in rats. In the first, cellular events involved in the development of ischemic renal atrophy induced by renal artery stenosis were recorded. One primary objective was to document the pathogenetic role that a distinct form of cell death, termed apoptosis, played in the development of renal tubular atrophy. A small, partially closed ligating clip was used to produce stenosis of the left renal artery, or a sham operation was performed. Animals were killed 2-28 days after operation. The ensuing ischemic renal atrophy was studied histologically and ultrastructurally, and apoptosis was counted in paraffin sections, using established criteria for its identification. Nuclear [3H]thymidine uptake was used as an indicator of cell proliferation. Morphometric studies recorded changes in area of transected tubular profiles. Correlation was sought between the morphological changes, data gained by the above quantitations, and the progressive reduction in renal mass that occurred during the experiment. Our results showed that during the acute phase (2-8 days), cell death was effected by both apoptosis and necrosis and increased tubular epithelial cell labeling and mitoses provided evidence of epithelial repair. During the chronic phase (10-28 days), when the mass of the ischemic kidney underwent significant reduction, cell death was effected by apoptosis alone, and the level of tubular epithelial cell labeling and mitosis returned to near normal. Intraepithelial macrophages were significant in removing the apoptotic bodies. Area of tubular epithelium was reduced in atrophic tubules, and it is proposed that this reduction may be explained by apoptotic cell deletion, as well as cell shrinkage. In the second study, evidence of regeneration was sought in atrophic kidneys after surgical reversal of renal artery stenosis and, in other animals, after unilateral nephrectomy of the contralateral kidney. Our results showed that regeneration, involving both hypertrophy and hyperplasia, was stimulated only by removal of the hypertrophied contralateral kidney and occurred whether or not stenosis of the renal artery was reversed. PMID- 2255187 TI - Expression of enolases in T cell tumors and Hodgkin's disease. AB - Frozen biopsy specimens taken from 30 cases with T cell tumors (8 with T cell acute lymphoblastic leukemia, 8 with T cell lymphoblastic lymphoma, and 14 with peripheral T cell lymphomas), and from 12 with Hodgkin's disease, were investigated using a direct immunohistochemical method to detect alpha-, beta- and gamma-enolases. Normal thymus and lymph node specimens with reactive lymphadenitis were also investigated. Subcortical thymocytes and the majority of deep cortical thymocytes showed reactivity of alpha-/beta-/gamma- approximately +/- -enolases, and medullary thymocytes and small lymphocytes in T zone areas of lymph node showed reactivity of alpha-/beta+/gamma- approximately +/- -enolases. Seven of the 8 cases with T cell acute lymphoblastic leukemia showed reactivity of alpha-/beta-/gamma(-)-enolases or alpha+/beta-/gamma(-)-enolases in leukemic lymphocytes, 7 of the 8 cases with T cell lymphoblastic lymphoma showed reactivity of beta(+)-enolase, and all 14 cases with peripheral T-cell lymphomas showed reactivity of alpha-/beta- approximately +/gamma(+)-enolases in lymphoma cells. All the 12 cases with Hodgkin's disease showed reactivity of alpha /beta+/gamma(+)-enolases in Reed-Sternberg and Hodgkin's cells. These results indicate the following: (a) The neoplastic cells of T cell acute lymphoblastic leukemia, T cell lymphoblastic lymphoma and peripheral T cell lymphomas present different expressions in each of these three categories. This may imply a difference of maturation and differentiation or activation among neoplastic T lymphocytes. (b) T lymphocytes may switch from alpha- to beta-enolase and from alpha- to gamma-enolase in the course of differentiation and activation. (c) It is worth noting that the Reed-Sternberg and Hodgkin's cells of Hodgkin's disease present an identical expression of enolases. PMID- 2255188 TI - Transplantability of myelocytomatosis MC29 virus-producing cell lines in chicken. Lateral transformation of host cells. AB - The transplantability of myelocytomatosis MC29 virus-producing chicken cell lines BR-3 and OB-1 was examined in 1-day-old chicks. Both cell lines, derived from the chicken cell line DU249, harbor nuclear genetic markers for drug resistance. When these cells were inoculated subcutaneously in the wing web of chicks, tumors developed at the site of injection in 65% of the cases. Propagation in culture of cells obtained by dispase treatment of the excised tumors, followed by selection for drug resistance, revealed that only a fraction of the tumors (27% and 60% for BR-3 and OB-1, respectively) resulted from the growth of the injected cells. The other tumors derive from the proliferation of host cells transformed by MC29 virus released by the injected cells. Tumor development subsequent to similar inoculation of 1-day-old chicks with cell-free virus stock further confirmed the tumorigenic capacity of MC29 at the site of injection. These results underline the need for the determination of tumor cell origin in studies using MC29 producing cell lines and highlight the advantage of using cells with drug resistant markers for such work. In the course of this study we determined by immunohistochemical criteria, the myogenic origin of some of the virally induced tumors. This is the first report of in vivo transformation of muscle cells by MC29-containing virus stocks in the newly hatched chick. PMID- 2255189 TI - Fibronectin profiles in normal and chronic wound fluid. AB - Fibronectin, an adhesion protein found in blood and tissues, is an important factor in wound repair. Recently, we began studies using sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting to compare fibronectin in the fluid of normal and chronic wounds. We found similar fibronectin profiles in suction blister fluid (2 normal volunteers) and mastectomy fluid (5 patients). There was primarily an intact 250 kilodalton fibronectin subunit and in addition some higher molecular mass fibronectin-containing complexes. On the other hand, fibronectin in diabetic ulcer wound fluid (2 patients) was partially degraded, and there was no intact fibronectin in stasis ulcer wound fluid (2 patients). The most prominent degradation products were 93 and 125 kilodalton polypeptides. When intact fibronectin was added back to stasis ulcer wound fluid, fragmentation occurred within 15 minutes at 37 degrees C indicating the presence of protease activity in the wound fluid. PMID- 2255190 TI - Expression of basic fibroblast growth factor in normal human tissues. AB - The distribution of basic fibroblast growth factor (bFGF) was studied immunohistochemically in fresh frozen sections of normal human tissues. Immunodetection was performed with a specific anti-bFGF mouse monoclonal antibody that was found to react with recombinant human bFGF in Western blot analysis, and to specifically neutralize the mitogenic activity of bFGF on bovine vascular endothelial cells. Expression of bFGF on normal human tissues was ubiquitously detected in the basement membranes of all size blood vessels, but was not found in epidermal or epithelial basement membranes of a variety of tissues tested. Intensity and patterns of localization in blood vessels was consistent in various tissues, but varied among different regions of the vascular bed. Whereas homogeneous and intense immunoreactivity were observed in large and intermediate size blood vessels, heterogeneity of expression was found in capillaries. The most intense immunoreactivity was observed in branching capillaries. Endothelial cell staining was heterogeneous and varied in different regions. Strong staining for bFGF was also found in cardiac muscle fibers, smooth muscle cells of mid-size blood vessels, the gut and the myometrium, in central nervous system neurons and cerebellar Purkinje cells, and on epithelial cells of the bronchi, colon, endometrium, and sweat gland ducts of the skin. The presence of bFGF in the extracellular compartment of a diverse variety of organs may play a role in angiogenesis. However, the function of bFGF in parenchymal cells remains to be determined. PMID- 2255191 TI - Generation and characterization of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells. AB - We have generated two mouse IgM monoclonal antibodies against rat microglia. The RMG-1 antibody recognized a 46-kilodalton cell-membrane antigen of ameboid microglia and cross-reacted with perivascular cells, monocytes/macrophages, and capillary endothelial cells of various organs but not with ramified microglia. In the normal brain, RMG-1-positive cells were found in the choroid plexus, periventricular area, corpus callosum, subarachnoid space and white matter of the cerebrum. The RMG-2 antibody recognized a 78-kilodalton cytoplasmic and cell membrane antigen of ameboid and ramified microglia and cross-reacted with perivascular cells and monocytes/macrophages of various organs but not with endothelial cells. A small number of RMG-2-positive cells were found in the choroid plexus and subarachnoid space on embryonic day 17. On postnatal day 1, RMG-2-positive cells appeared in the periventricular area and corpus callosum and then migrated to the internal capsule and thalamic nucleus. Thereafter, the number of RMG-2-positive cells increased, reaching a maximum on postnatal day 10 to 14, and gradually decreasing by postnatal day 28. These observations show that microglia are cells of monocytic lineage that enter the brain parenchyma late in embryogenesis or early in the postnatal period and lose at least some monocytic antigens to differentiate into ramified microglia. These monoclonal antibodies will provide useful tools to investigate the relation between microglia, perivascular cells, and endothelial cells in the brain and the kinetics of these cells in normal or pathologic conditions. PMID- 2255192 TI - Effects of tissue preparation on glomerular volume and capillary structure in the rat. AB - The effect of tissue preparation on glomerular volume in normal rats was assessed. In group 1 rats (N = 8), kidney tissue was obtained by immersion fixation of needle biopsy cores and excised slices from the left kidney and by perfusion-fixation of the remaining right kidney at close to ambient arterial pressure. In group 2 rats (N = 8), tissue was obtained by kidney perfusion at a supernormal pressure (approximately 165 mm Hg). Studies in group 1 showed that mean glomerular volume (VG) was not different in biopsy cores (1.07 +/- 0.13 x 10(6) mu 3) and in kidney slices fixed by immersion (0.92 +/- 0.09 x 10(6) mu 3). A significantly higher value for VG (1.51 +/- 0.18 x 10(6) mu 3) was obtained in kidneys perfusion-fixed at close to ambient arterial pressure. Morphometric studies showed that reduced VG in immersion-fixed tissue was associated with lowered values for peripheral capillary wall surface area (225 +/- 21 x 10(3) mu 2 versus 159 +/- 27 x 10(3) mu 2, p less than 0.05) and reduced mean capillary radius (4.5 +/- 6 mu versus 2.7 +/- 3 mu, p less than 0.05) compared with perfusion-fixed tissue. The data suggest that glomerular capillaries contract when tissue is immersion-fixed and shows that values for mean peripheral capillary wall surface area/glomerulus and mean glomerular capillary radius obtained in immersion- and perfusion-fixed tissue cannot be directly compared. Studies in group 2 showed that VG was not altered by perfusion at a supernormal pressure (1.40 +/- 0.16 x 10(6) mu 3) as compared with perfusion at ambient pressure (1.51 +/- 0.18 x 10(6) mu 3). Further studies in group 1, however, showed that values for VG obtained in paraffin-embedded tissue were approximately 40% lower than values for VG obtained in methacrylate-embedded tissue from the same kidneys. PMID- 2255193 TI - Football players susceptible to aseptic meningitis. PMID- 2255194 TI - Food preference article raises issues regarding transcultural research. PMID- 2255195 TI - Magnified light source assists health staff in nit, lice removal. PMID- 2255196 TI - The Moving Children Project: a conceptual, process-oriented model for skills development in children. AB - The Moving Children: Healthy Children (Moving Children) Project is a multidimensional conceptual model that provides elementary teachers a structure to incorporate mental and social concepts into a physical education program. The Moving Children Model focuses on four physical concepts which cover the full range of physical activity: body movement, object control, implement control, and game structure. The model helps children apply physical, mental, and social concepts to everyday situations. This objective is implemented by structuring the lesson to the environment and facilitating communication with follow-up classroom dialogue and journal assignments. As a result, successful, experimental learning reinforces a life-long attachment to movement and principles of health promotion. PMID- 2255197 TI - Eating disorders: a framework for school nursing initiatives. AB - Anorexia nervosa and bulimia nervosa are complex illnesses identified with increased frequency among adolescents, particularly adolescent females. Eating disorders can have serious health consequences and school nurses can play an important role in primary, secondary, and tertiary prevention. An overview of eating disorders within a theoretical framework for school nursing practice is presented, and a case management role within an educational setting is proposed for school nurses. Etiology, classification, and signs and symptoms are highlighted for application in schools. Recommendations are made for curriculum planning and involvement of other school professionals. Treatment for eating disorders is most successful when initiated early in the illness. Schools provide a natural forum to reach adolescents, and school nurses, with their biopsychosocial emphasis, are uniquely prepared to address these disorders. PMID- 2255199 TI - Health behavior correlates of depression in a sample of high school students. AB - Frequency of symptoms of depression and selected health-related practices and events were measured in a sample of 219 high school students. Students reported numerous symptoms of depression. Relative proportions of boys and girls reporting symptoms of depression were not significantly different. However, girls reported experiencing more severe depression than their male counterparts. Depression correlated significantly with several of the 22 health practices and states of affect examined. Both the determinants and manifestations of depression in adolescent cohorts require in-depth investigation. Possible implications for school health personnel are discussed. PMID- 2255198 TI - School-based cardiovascular health promotion: the child and adolescent trial for cardiovascular health (CATCH). AB - The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a multisite intervention research study that builds on significant progress made in school health education research in the 1980s. The study has three phases: Phase I deals with study design, intervention, and measurement development, Phase II involves the main trial in 96 schools in four states, and Phase III focuses on analysis. The intervention program targets third-fifth grade students and focuses on multiple cardiovascular health behaviors, including eating habits, physical activity, and cigarette smoking. Classroom curricula, school environmental change, and family involvement programs are developed for each grade level and behavioral focus. This paper describes Phase II of CATCH with a rationale for cardiovascular health promotion with youth. The process of change that appears to be necessary for school-based health promotion and that will be tested in CATCH are presented as a framework to guide these efforts. PMID- 2255200 TI - First family planning visit in school-based clinics. AB - The timing of the first family planning visit for 144 female adolescents using school-based clinics in four St. Paul, Minn., high schools was studied. Mean delay time for the sample was 11.4 months and the median was 7.8 months. Almost 50% of the sample arrived within two months of either a planned onset of sexual intercourse (virgin group) or a recent start of sexual activity (short delay group). Early onset of sexual activity (v age 15) was more prevalent among long delayers (47.9%) than among short delayers (21.1%). Longer delayers were more likely to come from the lowest socioeconomic groups. Short delayers and longer delayers were equally likely to have been motivated to attend the clinic because they feared they were pregnant. Reasons for choosing this clinic over others reflected the importance of confidentiality, comprehensiveness of services, and the specific adolescent orientation of care. PMID- 2255201 TI - Teaching critical thinking through the mock trial. PMID- 2255202 TI - The school nurse and sport nutrition for the adolescent athlete. PMID- 2255203 TI - "AIDS speak:" sensitive and accurate communication and the HIV epidemic. PMID- 2255204 TI - Effects of chronic oral administration in mice of the gut-stimulating crystals of Croton penduliflorus seed oil. AB - Crystals from Croton penduliflorus seeds (CPC) were administered at weekly intervals in two doses (7 mg/kg and 21 mg/kg) by gastric intubation to mice over 12 weeks. CPC induced purgation in the treated mice, with the higher dose having a more profound effect. Mice treated with CPC developed skin lesions with swollen scrotums. There were significant changes in the PCV, Hb and plasma proteins of treated mice. Gangrene of the tail with subsequent sloughing was observed, particularly in the low dose group. Mice in the low dose group also experienced retarded growth. A significant clinical finding in the treated mice was abortion during late pregnancy and 100% fetal mortality. It was concluded that, apart from its purgative effect, CPC can cause toxic effects in chronic administration. Use in pregnant women should be discouraged. PMID- 2255205 TI - Hepatoprotective effects of astraglus root. AB - Oral administration of an ethanol extract of the root of Astragalus membranaceus alleviated liver injury induced by stilbenemidine. Pre-administration in mice reduced elevated SGPT levels and subacute toxicity of stilbenemidine, decreased pentobarbital-induced loss of righting reflex and protected hepatic cells from pathological changes. PMID- 2255206 TI - Hypotensive action of a Coscinium fenestratum stem extract. AB - A 50% ethanol extract of Coscinium fenestratum stem material (AECF) has been found to possess hypotensive action in anaesthetised dogs, rats and guinea pigs in a dose-related pattern. The fall in blood pressure was not modified by alpha and beta adrenergic blockers, cholinergic and histaminergic antagonists or by ganglion blocking agents. The effect was more pronounced in spinal-transected animals. AECF non-specifically inhibited the pressor responses to epinephrine, norepinephrine, DMPP and depressor responses to acetylcholine and histamine. AECF failed to exhibit any hypotension when administered via cannula into the lateral cerebral ventricle. Given orally to mice, AECF did not exhibit grossly observable central nervous effects up to doses of 800 mg/kg. The oral LD50 was estimated to be 1200 mg/kg in mice. PMID- 2255207 TI - Ethnopharmacology of rhinoceros horn. I: Antipyretic effects of rhinoceros horn and other animal horns. AB - Intraperitoneal administration of an aqueous extract of rhinoceros horn at 5, 2.5 and 1 g/ml, showed a significant antipyretic effect in rats with hyperthermia induced by subcutaneous injection of terpentine oil. Similar assays with extracts of the horns of saiga antelope, water buffalo and cattle at 5 g/ml also caused a significant drop in fever; however, at 1 g/ml, only saiga antelope horn produced an antipyretic action. PMID- 2255208 TI - Molluscicidal trials and correlation between the presence of Tetrapleura tetraptera in an area and the absence of the intermediate hosts of schistosomiasis and fascioliasis in southwest Nigeria. AB - A schistosomiasis research project, carried out in Southwest Nigeria, yielded data by which it was possible to relate snail recovery from potential transmission sites to the presence or absence of Tetrapleura tetraptera. A significant negative correlation with snail numbers was found for distance of T. tetraptera from transmission sites and fruiting of the trees when these variables were tested individually. There were no significant differences between individual variables such as pH, Ca2+ concentrations and temperatures for these snail habitats but these variables produced significant positive correlation with the number of snails recovered. Thus, the presence of T. tetraptera appeared to be the most important limiting factor for the presence of snails. Aqueous extracts of T. tetraptera were effective as a molluscicide against Bulinus globosus and Lymnaea natalensis. However, pollution of the environment by oils reduced or abolished the molluscicidal activity of T. tetraptera. The results indicate that the planting of T. tetraptera has potential for the local control of schistosomiasis. PMID- 2255209 TI - Pharmacological assay of Casearia sylvestris. I: Preventive anti-ulcer activity and toxicity of the leaf crude extract. AB - An ethanol extract of the leaves of Brazilian Casearia sylvestris, given orally, inhibited gastric secretion in pylorus-ligated rats. At a prophylactic dose of 57.5 mg/kg, the extract showed a reduction of gastric juice more effective than misoprostol (500 micrograms/kg). In reducing hydrochloric acid output, the extract was less effective than misoprostol, cimetidine (32.0 mg/kg) and atropine (5.3 mg/kg). With the extract, the pH of the stomach contents was not significantly different from that of controls. Stress-induced lesions produced by restraint and water immersion were significantly prevented by the extract for all levels of severity when compared with the controls. The extract appeared more effective than misoprostol in suppressing light lesions, was equivalent to cimetidine and misoprostol for moderate lesions, and less effective than cimetidine and misoprostol for severe lesions. Toxicological experiments indicated a low acute toxicity, confirmed by subchronic daily testing. The oral LD50 value of greater than 1840 mg/kg was over 32 times higher than the antiulcerogenic ED50 (57.5 mg/kg). PMID- 2255210 TI - Effect of Momordica charantia fruit juice on streptozotocin-induced diabetes in rats. AB - The oral hypoglycaemic activity of Momordica charantia fruit juice was investigated in rats with streptozotocin-induced diabetes. Oral administration of the juice (10 ml/kg for 30 days) did not show a significant effect, either acute or cumulative, on the ability to tolerate an external glucose load. The glycosylated haemoglobin concentrations were significantly elevated in both juice treated and untreated diabetic rats and there was no significant difference between the two groups. Viable beta-cells capable of secreting insulin upon stimulation appear to be required for M. charantia to exert its oral hypoglycaemic activity. PMID- 2255211 TI - A hypotensive procyanidin-glycoside from Rhamnus lycioides ssp. lycioides. AB - A lyophilized hot water extract of the aerial parts of Rhamnus lycioides L. (Rhamnaceae) produced a lowering of systemic arterial blood pressure in normotensive anaesthetized Wistar rats. An activity-guided fractionation of the methanolic extract led to the isolation of a tetrameric procyanidin-glycoside which produced a clear dose-dependent hypotensive response (1.5-6 mg/kg i.v.). This principle was characterized using acid hydrolysis, thiolytic degradation and spectroscopic methods. It consisted of four flavanol units with a 2,3-cis configuration and with a O-beta-d-glucosylpyranoside function on the epicatechin terminal unit. The interflavan linkage was (4-8). PMID- 2255212 TI - Effects of fig latex on lipid peroxidation and CCl4-induced lipid peroxidation in rat liver. AB - The oral and intraperitoneal effects of fig milk latex on lipid peroxidation and CCl4-induced lipid peroxidation in liver homogenates of female rats were investigated. Oral treatment had no effect, while i.p. administration produced a significant increase in hepatic lipid peroxidation. When the latex was given before CCl4 treatment; it produced no protective effect against CCL4-induced hepatotoxicity. Addition of the latex to the incubation mixture produced a dose dependent increase in lipid autoxidation, while the chloroform and ether extracts of the latex, as well as heated latex, had no effect on hepatic lipid autoxidation. PMID- 2255213 TI - Screening of Artemisia absinthium for antimalarial effects on Plasmodium berghei in mice: a preliminary report. PMID- 2255214 TI - Trypanocidal potentials of African woody plants: in vitro trial of Khaya grandifoliola seed extracts against Trypanosoma brucei brucei. PMID- 2255215 TI - Nicotine-replacement therapy with use of a transdermal nicotine patch--a randomized double-blind placebo-controlled trial. AB - The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement, self-help material, and weekly visits with a nurse for 6 weeks. Nicotine-replacement therapy with a transdermal nicotine patch (Nicolan) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group (77% versus 39%; P = 0.002) among subjects who were smoking at least 20 cigarettes per day at baseline. Although most subjects who used the active nicotine patches had skin reactions, the reactions were primarily mild. For use of both active and placebo patches, the level of patient compliance was high. Among subjects who continued to smoke, the use of cigarettes was decreased to less than 50% of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches. Outcomes beyond 6 weeks showed a substantial relapse rate in both groups. Thus, when nicotine-replacement therapy is provided, a need exists for concurrent behavioral intervention and training for prevention of a relapse, neither of which was part of this protocol. PMID- 2255216 TI - Hamman-Rich syndrome revisited. AB - In this article, we retrospectively review 29 cases of Hamman-Rich syndrome. As in some other recent reports, we have used the term "acute interstitial pneumonia" to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias, particularly idiopathic pulmonary fibrosis. Of the 29 patients, 12 survived, some after a long and complicated hospitalization. The histologic features were those of organizing diffuse alveolar damage, and some patients, including survivors, had extensive fibroblastic distortion of lung parenchyma. The overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general. PMID- 2255217 TI - Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. AB - Between 1982 and 1989, 19 patients with gynecologic carcinoma, paraneoplastic cerebellar degeneration, and seropositivity for anti-Purkinje cell cytoplasmic antibodies were identified at our institution. Seven of the patients had no clinical, computed tomographic, or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti-Purkinje cell antibodies were found in their serum; all had high-grade adenocarcinoma. Cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients. The cancers were 14 ovarian, 2 fallopian tube, 2 surface papillary, and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node. Two remarkable surgical observations in patients with high-grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume. A comparison of the 8 patients who had primary stage III cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group (P = 0.05). Anti-Purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer. The small metastatic volume in the face of high-grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor (presumably cross reactive with cerebellar cells) may impair the metastatic process. Earlier diagnosis and treatment of cancer, based on prompt serologic testing, may offer an improved neurologic and oncologic prognosis. PMID- 2255218 TI - Safety of same-day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert-butyl ether in dogs. AB - Passage of stone fragments after extracorporeal shock wave lithotripsy (ESWL) of gallstones has resulted in biliary colic, duct obstruction, and pancreatitis in some patients. Rapid dissolution of these fragments with methyl tert-butyl ether (MTBE) may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer. This study examines the safety of same-day ESWL fragmentation and MTBE dissolution of surgically implanted human gallstones in 15 dogs. The animals were randomly assigned to one of four treatment groups to assess MTBE absorption from the gallbladder and to observe hematology and chemistry profiles after 0, 400, and 1,200 shock waves from a lithotriptor followed by MTBE dissolution therapy. They were sacrificed either immediately after treatment (12 dogs) or 2 weeks later (3 dogs). The results demonstrated that although ESWL causes moderate trauma to the gallbladder, this did not result in increased MTBE absorption or histologic evidence of mucosal disruption. Blood profiles demonstrated an increase in only the level of aspartate aminotransferase. The three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material. In all animals, severe injury occurred where shock waves passed through lung or air-filled colon. This study suggests that same-day sequential fragmentation of gallstones by ESWL followed by dissolution of stone fragments with use of MTBE may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones. PMID- 2255219 TI - Medical symbols: the ankh. PMID- 2255220 TI - Endorectal ultrasonographic staging of rectal carcinoma. AB - Endorectal ultrasonography is a valuable imaging method for examination of the rectum and perirectal tissues. We assessed 50 patients with known rectal carcinoma prospectively by using a 7.0-MHz endorectal transducer to determine the depth of invasion of the rectal wall by tumor and the presence of lymphadenopathy. Tumors were staged by using the Astler-Coller modification of the Dukes staging system, and the results were compared with histologic staging of the surgical specimen. Ultrasonography had an accuracy of 80%, a sensitivity of 92%, and a specificity of 76% for detection of invasion of the perirectal fat. Ultrasonography was sensitive in the detection of perirectal lymphadenopathy but was not specific in distinguishing benign from malignant nodes. PMID- 2255221 TI - Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature. AB - Hypernatremia is a common electrolyte disturbance, most often caused by volume depletion. Hypernatremia due to sodium excess occurs less frequently, and fatal hypernatremia solely from ingestion of table salt is rare. We describe a 41-year old man who had seizures and hypernatremia after ingestion of a supersaturated salt water solution intended for gargling. He had consumed approximately a third cup of table salt (approximately 70 to 90 g of salt or 1,200 to 1,500 meq of sodium). His initial serum sodium concentration was 209 meq/liter. Hypotonic fluid therapy was given to provide free water and to correct the hypernatremia gradually. Our patient, however, failed to recover from the initial insult and died 3 days later. Review of the literature revealed 10 adult and 20 pediatric cases of hypernatremia attributable to exogenous intake of salt. The type of therapy (fluid or peritoneal dialysis), the type of fluid used, and the rate of correction of hypernatremia did not influence survival. The age of the patient and the initial serum sodium concentration were the most important prognostic indicators. Both very young patients and those with lesser degrees of hypernatremia had a better rate of survival than did other patients. In addition, our review illustrates the surprisingly small amount of salt that can cause severe hypernatremia and the danger of using salt or saline as an emetic. PMID- 2255222 TI - Selected neurologic complications of pregnancy. AB - Many neurologic disorders, such as eclampsia, pseudotumor cerebri, stroke, obstetric nerve palsies, subarachnoid hemorrhage, pituitary tumors, and choriocarcinoma, can develop in the pregnant patient. Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion. Pseudotumor cerebri can be associated with serious visual complications; thus, the therapeutic goal is to prevent loss of vision. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis. Lumbar disk prolapse is common in pregnant patients, and lumbosacral plexus injuries can occur during labor or delivery. In addition, peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy. The incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10,000 patients, a rate 5 times higher than in nonpregnant women. Because of a proliferation of prolactin-secreting cells, the pituitary gland can enlarge dramatically during pregnancy, a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic. The incidence of choriocarcinoma is 1 in 50,000 full-term pregnancies but 1 in 30 molar pregnancies. This malignant tumor has a high rate of cerebral metastatic lesions. In addition to these disorders that develop during pregnancy, the pregnant state can affect numerous preexisting neurologic conditions, including epilepsy, headaches, multiple sclerosis, myasthenia gravis, spinal cord injury, and brain tumors. We discuss advice for patients with such conditions who wish to become pregnant, recommendations for medical and surgical management, and surgical considerations for neurologic complications during pregnancy. PMID- 2255223 TI - Nicotine-replacement therapy in cessation of smoking. PMID- 2255224 TI - Back to the future: the Hamman-Rich syndrome and acute interstitial pneumonia. PMID- 2255225 TI - Interpretation of hospital mortality rates: the current state of the art. PMID- 2255226 TI - Inflammatory bowel disease. PMID- 2255227 TI - Our foods are safe! PMID- 2255228 TI - Immunohistochemical identification of proliferating cells following dimethylnitrosamine-induced liver injury. AB - The present study is concerned with changes in the number and localization of S phase cells in the liver of rats exposed to dimethylnitrosamine (DMN). S-phase cells were detected by immunohistochemistry after injection of bromodeoxyuridine (BrdU) and exposure of paraffin sections of liver tissue to the antibody anti BrdU. With respect to controls, the number of S-phase cells increased four to fivefold in DMN-treated animals in the first week of treatment and remained significantly higher thereafter, in association with the formation of septa. At all times, the labelling index was higher in littoral cells than in hepatocytes. No labelling was observed in biliary cells. This behaviour is different from that reported in other situations, for instance in regeneration after partial hepatectomy, which suggests that besides hepatocytes and littoral cells replacement, an involvement of the latter cell line in the inflammatory reaction, synthesis of extracellular matrix components and formation of septa may account for this particular pattern. PMID- 2255229 TI - Changes in sensitivity of hepatocytes isolated from regenerating rat liver to the growth inhibitory action of transforming growth factor beta. AB - Transforming growth factor beta (TGFB) is a potent inhibitor of DNA synthesis in adult rat hepatocytes in vitro. In the present study, the response of hepatocytes from normal or regenerating rat liver to TGFB was determined. TGFB inhibited DNA synthesis uniformly in hepatocytes from both groups in the absence of EGF. However, hepatocytes from 3 h regenerating liver maintained for 3 days in the presence of EGF were less sensitive to the growth-inhibitory action of TGFB. [3H] thymidine incorporation was inhibited at 20 pM TGFB by only 7% in hepatocytes from 3 h regenerating liver compared with 70% in normal hepatocytes. By increasing the dose of TGFB to 100 pM, however, the full inhibitory response was restored. Reduced sensitivity was also found when the nuclear labelling index was determined, but no change was observed in cells from rats 3 h following sham hepatectomy. The change in sensitivity to TGFB required the presence of 5 ng/ml EGF or greater. Within a further 24-48 h in culture, the response to lower doses of TGFB was at least partially restored. While the present experimental design cannot directly confirm the role of TGFB as a paracrine inhibitor of liver growth in vivo, the data are compatible with this hypothesis. PMID- 2255230 TI - Different outcomes of chronic hepatitis delta virus infection in woodchucks. AB - Hepatitis delta virus (HDV) superinfection of woodchuck chronic carriers of woodchuck hepatitis virus (WHV) results in acute and chronic disease. The different courses of disease mimicked the outcome of human HDV superinfection, making woodchucks valuable models for clinical studies of HDV. Ten of 11 woodchuck chronic carriers of WHV superinfected with HDV developed acute HDV infection with markers of viral replication in the serum and liver. One animal (DW128) had no serological markers of acute HDV infection. Nine of 11 (82%) superinfected animals developed chronic HDV infection. An unusual course of chronic HDV infection occurred in one woodchuck (DW128): no serum markers of acute or chronic HDV infection appeared but HDV RNA was detected in the liver, indicating that chronic HDV infection can occur without serological markers. PMID- 2255231 TI - Inhibitory effects of hepatitis B virus antigen on induction of lymphokine activated killer cell activity. AB - We investigated the inhibitory effects of purified recombinant hepatitis B virus (HBV) surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine-activated killer cell (LAK) activity. Either peripheral blood mononuclear cells (PBMCs) or CD16+ CD3- LAK precursors, both of which were pre-incubated with interleukin-2 (IL-2) and rHBsAg or rHBcAg for 72 h, showed a significant decrease in LAK cytotoxicity against Daudi cells, in comparison to the results recorded in the presence of IL-2 alone, or IL-2 and E. coli extracts. This inhibitory effect was dose-dependent and was observed to be time-dependent from 24 to 72-h-cultures with these HBV antigens. This influence was not mediated with either adherent cells or other accessory cells. The proliferative reaction of either PBMCs or the LAK precursors after being cultured with IL-2 and rHBsAg or rHBcAg for 72 h was significantly diminished compared with the levels of reaction of those cells after a 72-h culture with IL-2 alone or with IL-2 and E. coli extracts. The levels of IL-2-driven IL-2 receptor (p55) expression of either PBMCs or the LAK precursors in the presence of rHBsAg or rHBcAg were higher than the levels seen in the absence of these HBV antigens. These results suggest that HBsAg and HBcAg may inhibit the induction of LAK activity by interfering with the proliferative reaction of the LAK precursors to IL-2 without inhibiting the IL-2 receptor expression of the cells. Cytofluorographic analysis of PBMCs, cultured with rIL 2, showed lower percentages of CD3+ and CD16+ cells in the presence of these HBV antigens than those in the absence of antigens. PMID- 2255232 TI - Development of the "activated" high resolution 1H MR spectrum in murine T cells and B cells occurs in G1 phase of the cell cycle. AB - T and B lymphocytes stimulated with mitogens develop 1H MR spectra characteristic of triglycerides in an isotropic environment. These distinctive signals, which are also observed in malignant cells, cannot be suppressed by compounds which inhibit progression through the cell cycle. Cellular proliferation is thus not essential for the development and maintenance of high resolution lipid spectra in activated cells. PMID- 2255233 TI - Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. AB - In this study quantitation of the degree of deficiency of the blood-brain barrier (BBB) in patients with multiple sclerosis or brain tumors, by using MRI, is shown to be possible. As a measure of permeability of the BBB to Gadolinium-DTPA (Gd DTPA) the flux per unit of distribution volume per unit of brain mass was used. This quantity was found by introducing the longitudinal relaxation rate (R1) as a measure of concentration of Gd-DTPA in the brain tissue in the mathematical model for the transcapillary transport over the BBB. High accordance between the observed data points and the model was found, and the results were comparable to results obtained from similar studies using positron emission tomography. The improved possibility of quantitating the defect of the BBB by MRI may give new information about pathogenesis or etiology, and leads to improved methods in monitoring the efficacy of treatments in intracranial diseases. PMID- 2255234 TI - Magnetohydrodynamics of blood flow. AB - The changes in hydrostatic pressure and electrical potentials across vessels in the human vasculature in the presence of a large static magnetic field are estimated to determine the feasibility of in vivo NMR spectroscopy at fields as high as 10 T.A 10-T magnetic field changes the vascular pressure in a model of the human vasculature by less than 0.2%. An exact solution to the magnetohydrodynamic equations describing a conducting fluid flowing transverse to a static magnetic field in a nonconducting, straight, circular tube is used. This solution is compared to an approximate solution that assumes that no magnetic fields are induced in the fluid and that has led previous investigators to predict significant biological effects from static magnetic fields. Experimental results show that the exact solution accurately predicts the magnetohydrodynamic slowing of 15% NaCl flowing transverse to 2.3- and 4.7-T magnetic fields for fluxes below 0.5 liter/min while the approximate solution predicts a much more retarded flow. PMID- 2255235 TI - Double EPI sequence with 180 degrees RF pulses. AB - Rapid imaging can be performed in the magnetic field of low homogeneity using 180 degrees RF pulses instead of gradient reversals to form a series of differently phase-encoded echoes. A modified version of pi-pulsed EPI which samples the data in two complementary shots was designed. Its advantage for objects of short T2 is illustrated by phantom images. PMID- 2255236 TI - The relation of low frequency restoration methods to the Gerchberg-Papoulis algorithm. AB - In magnetic resonance imaging, low frequency components can be allowed to saturate the analog to digital converter to reduce the quantization noise. These components can be estimated using least squares error estimation based low frequency restoration methods or the iterative Gerchberg-Papoulis algorithm. In this paper, we show the relationship between the closed form estimation methods and the iterative algorithm, propose a method for improving the speed of iteration, and discuss the advantages and disadvantages of two types of methods. PMID- 2255237 TI - An in vivo NMR imaging determination of multiexponential Hahn T2 of normal lung. AB - We describe the first in vivo imaging determination of normal lung tissue's multiexponential transverse magnetization decay. Normal spontaneously breathing rats were used for the measurements. To obtain motion-insensitive images, we used a modified line scan imaging technique which we call the interleaved line scan (ILS). The ILS overcomes the following difficulties associated with imaging lungs: low signal-to-noise ratio (S/N) due to lung's low proton density and short T2 decay, artifacts associated with cardiac and respiratory motion, and excessively long imaging times with conventional line scan techniques. Using the ILS, a 16-line 32-average image with an 8-s repetition time requires 4.3 min. From a series of 16 Hahn spin-echo images with echo times ranging from 16 to 90 ms, we obtained a two-component T2 decay for normal peripheral lung tissue. The measured fast and slow T2 components were 9.5 +/- 1.0 and 34 +/- 5.0 ms for the right lung and 9.0 +/- 1.5 and 32 +/- 4.5 for the left lung. The relative magnetization for the slow T2 component was 7.0 +/- 4.5% for the right lung and 10 +/- 3.0% for the left lung. PMID- 2255238 TI - CPMG imaging sequences for high field in vivo transverse relaxation studies. AB - Two-dimensional Fourier transform Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.9-T and 1.5-T imaging systems in order to test their ability to characterize in vivo transverse decay curves (TDCs). Both hard- and soft-pulse CPMG imaging sequences, consisting of up to 128 echoes with echo spacings of approximately 10 ms were developed, implemented, and tested. These sequences provide one of the most detailed samplings of TDCs from image data sets reported to date. Good agreement between image-extracted T2 values and spectroscopically obtained T2 values of NiCl2-doped saline solutions was found with both hard- and soft-pulse sequences. In vivo TDCs were extracted from rabbit and human image data sets. For several tissues, biexponential TDC fits provided considerable improvement over monoexponential fits and the sensitivity of the fitting parameters to positive baseline offsets was examined. With the time coverage of the relaxation decay curves available from these sequences, the TDCs from white matter in humans appear largely monoexponential while those from cortical grey matter demonstrate biexponential behavior. PMID- 2255239 TI - Magnetic susceptibility shift selected imaging: MESSI. AB - Paramagnetic compounds are often used to enhance contrast in MRI by virtue of their increase in the kinetics of the relaxation of water 1H magnetization. Here, we demonstrate a method for contrast enhancement which is based on the resonance frequency shifts caused by the bulk magnetic susceptibility (BMS) effects of such compounds. This involves the frequency selective excitation in the absence of field gradients, during the imaging sequence, of a portion of the water 1H resonance which is rendered inhomogeneous by BMS shifts only. The image which results is of that portion of the sample which gives rise to the portion of the spectrum excited. A phantom sample which simulates some aspects of tissue, particularly blood vessels with different orientations in the magnetic field, was prepared. The contrast enhancement exhibited here avoids some of the distortions attendant to the use of paramagnetic reagents. This new approach can, in principle, utilize the natural BMS differences found in all tissue. PMID- 2255241 TI - Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy. AB - Spatially localized phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been applied to the study of the normal canine myocardium to measure the relative content of high energy phosphates across the left ventricular wall. Transmural NMR data were acquired in five voxels spanning the wall of the left ventricle using the FLAX-ISIS technique. The validity of the FLAX-ISIS approach in acquiring localized spectra for transmural studies and in providing quantitative information from the localized spectra was examined rigorously by studies involving phantoms, intact rats, and the canine myocardium in vivo. The results indicated that (1) this technique yields spatially resolved spectra with partial overlap between adjacent voxels and virtually no overlap between every other voxel; (2) in the canine heart, signals from subepicardium, midwall, and subendocardium can be detected separately without cross contamination; and (3) relative metabolite contents within a voxel and among voxels can be quantitated. Transmural 31P NMR spectra were acquired with cardiac gating on 29 separate animals either at early systole or late diastole, and at three different workloads with the heart rate peak systolic pressure product (RPP) increasing from 6000 mmHg/min to 35,000 mmHg/min. The data revealed that in the normal canine myocardium, the creatine phosphate (CP) content and the CP/ATP ratio was significantly lower in the subendocardium than in the subepicardium. ATP levels were transmurally constant. Both the CP content and the CP/ATP ratio measured for each voxel remained unaltered in relation to either the phase of the cardiac cycle or approximately fourfold increase in workload. Free ADP levels calculated for each voxel showed that ADP was relatively higher in the subendocardium than the subepicardium, and in all transmural layers was higher than its apparent Km for oxidative phosphorylation. In this domain changes in ADP content with workload and MVO2 are not expected and were not observed. PMID- 2255240 TI - Magnetic resonance imaging of blood vessels at high fields: in vivo and in vitro measurements and image simulation. AB - Unusually high image contrast in vivo magnetic resonance imaging of the brain becomes observable at high magnetic fields when the blood oxygenation level is lowered. The cause of the contrast has been attributed to a magnetic susceptibility effect induced by paramagnetic deoxyhemoglobin in red cells. When the cylinder axis of a blood vessel is not parallel to the main magnetic field, the susceptibility difference produces varying local fields around the blood vessel. In gradient-echo images, not in spin-echo images, these local fields cause intravoxel dephasing of the water signal of the surrounding tissue. This description of the contrast enhancement has been confirmed by a series of in vitro blood sample experiments and image simulations. A predicted contrast change has been demonstrated in brain images of a mouse placed at two different orientations in the magnet. From the simulated images, the dependence of the contrast on the field strength has been estimated. PMID- 2255243 TI - Free flap circulation and modes of arterial insertion: an experimental study. AB - Using electromagnetic flowmetry, the circulation through free flaps was studied in an experimental animal model. It was demonstrated that the total circulation of blood through a free flap is not affected by the establishment of an arterial through-flow or end-flow model in the recipient bed. PMID- 2255242 TI - Digital replantation in children: a long-term follow-up study. AB - This paper reports a series of 14 cases of digital replantation in children who had had a total of 17 digits traumatically amputated. All but two digits survived, for an overall success rate of 88%. The length of follow-up was between 3 and 14 years (average 8 years). Sensory recovery of all digits was satisfactory. The mean growth rate of replanted digits relative to contralateral digits was 86%. Twelve cases had an excellent result, and one case had a good result. Digital replantation in children is recommended when feasible. PMID- 2255244 TI - Microarterial synthetic graft repair: interstitial cellular components. AB - Although the histologic changes occurring during healing on the lumen surface of large vessel synthetic vascular grafts have been well characterized, the cells populating the interstices of microvascular grafts have not been examined in detail. Since microvascular grafts are required to provide vascular continuity under quite different physiological and hemodynamic conditions as compared with large vessel grafts, these interstitial cells within the synthetic graft material may also vary as a function of graft size. Monoclonal antibodies, light microscopy, and scanning and transmission electron microscopy were used in this study to identify the cells present within the 30-microns pores of 1-mm diameter polytetrafluoroethylene and replamineform silicone rubber grafts. Identified cells included few capillary endothelial cells enclosing erythrocytes, rare proliferating endothelial cells, few macrophages, rare foreign body giant cells, and a majority of fibroblasts. There was no evidence of smooth muscle cells or myofibroblasts within the interstices of these microvascular prostheses 12 weeks after implantation in the rabbit central ear artery. The graft types differed by the presence of foreign body giant cells and more densely packed collagen between cells in the replamineform silicone rubber graft interstices. PMID- 2255245 TI - Reverse-flow vascularized fibular graft: a new method. AB - The reverse-flow island flap is a relatively recent concept. We have applied this concept to the vascularized bone graft. We report a new method of the reverse flow vascularized fibular graft for two patients with a pseudarthrosis and massive bone defect of the tibia. The peroneal artery and venae comitantes were severed proximally and elevated with the fibula while maintaining distal vascular continuity. The reverse-flow vascularized fibula was grafted to the posterior aspect of the bone defect of the tibia. Bony union was obtained in both cases. The reverse-flow vascularized fibular graft has many advantages compared with free vascularized fibular graft. PMID- 2255247 TI - Contribution of microsurgery in transplantation progress. PMID- 2255246 TI - Treatment of migraine headache in a postoperative microsurgical patient. AB - Immediately following a double-toe transfer to her hand, a 40-year-old woman developed a severe migraine headache unrelieved by narcotics. Medical consultation was obtained, and available medical treatments were discussed in relation to their possible effects on the patient's recent microvascular procedure. Intravenous steroids were administered, with resolution of the headache. This case illustrates an approach to the management of medical problems in which treatment options are weighed against their possible microsurgical effects. PMID- 2255248 TI - Comparative study of secretion by vagotomized and isotransplanted stomachs in the rat. AB - An acute observation of gastric secretion by syngeneic stomach transplants in Lewis male rats was compared to the gastric secretory fate of normal, pylorus ligated, vagotomized, and combined pylorus ligation and vagotomized Lewis rats. A 5 day observation was sufficient before sympathetic fibers and vagal channels could be regenerated. A total of 36 rats were divided into five groups of which group I (ten normals), group II (five vagotomized), group III (pylorus-ligated), group IV (six vagotomized and pylorus-ligated), and group V (five syngeneic stomach-transplanted, five animals served as donors), and those stomachs were intubated to collect gastric juice by housing animals in Bollman cages. Whereas group V animals secreted a mean 24 hr gastric juice volume of 12.5 +/- 6.4 ml with free acid secretion of 0.15 +/- 0.01 mEq/24 hr, animals in groups I, II, III, and IV secreted 24.4 +/- 2.9 ml, 23.3 +/- 1.1 ml, 25.5 +/- 3.4 ml, 22.4 +/- 0.5 ml, respectively, for 24 hr periods with free acid secretions of varying rates. From these observations, the transplanted stomach mean secretory rate averaged half that of the normal stomach. PMID- 2255249 TI - A tribute to the late Dr. Ryo Shimazu: a chronic bowel allograft model in the rat. AB - A chronic model of bowel allotransplantation is described. End-to-end microvascular anastomosis between superior mesenteric vessels was utilized. The recipient splenic vein was preserved to avoid postoperative pancreatitis. Euro Collins solution was used to flush the vasculature in the lumen of the transplant. Low-dose cyclosporine was used for immunosuppression. With experience, 89% long-term survival was achieved. PMID- 2255250 TI - Small bowel transplantation. AB - Small intestinal transplantation has had several clinical attempts based on extensive experimental work during the past two decades. Several models, such as auxiliary (heterotopic) or orthotopic models, have been developed in regard to problems with graft immunology and function. The question of mesenteric-portal or mesenteric-caval graft drainage was raised, and the answer seems to be open. Concerning lipid absorption, interest was directed to the reconstitution of lymphatic vessels, because orally administered cyclosporine A is absorbed by the lipid mechanism. Carbohydrate digestion and absorption are used for determination of graft function and for monitoring graft rejection. This article summarizes these problems and deals with the surgical procedure of small bowel transplantation in the rat. PMID- 2255251 TI - Small bowel transplantation in the rat with immediate restoration of intestinal continuity. AB - Compared with other rat transplant models, small bowel transplantation (SBT) is associated with higher peritransplant morbidity and mortality. We describe a two stage technique of SBT in the rat that minimizes perioperative complications and also allows immediate restoration of intestinal continuity. Inbred Lewis strain rats were used as donors and recipients. A one-stage technique was originally adopted whereby the distal 50% of the jejunoileum was transplanted followed by near-total resection of the native small intestine and restoration of intestinal continuity. Among 20 rats transplanted with this technique, only one survived longer than 30 days. With the two-stage technique, transplantation of the donor jejunoileum in continuity was performed, followed by native enterectomy 7 days later. With the two-stage technique 17 of 20 rats survived indefinitely (greater than 50 days). Other important technical modifications are described. In the hands of a skilled microvascular surgeon, the two-stage SBT technique results in consistently improved survival and minimal morbidity. PMID- 2255252 TI - Influence of the length of the small bowel graft on the severity of graft versus host disease. AB - The influence of the length and origin of a small bowel graft on graft versus host disease (GVHD) was studied in 33 (Lewis x brown Norway) F1 hybrids transplanted with different types of Lewis small bowel grafts. Recipients of an entire small bowel graft (N = 9), a jejunal graft (N = 6), or an ileal graft (N = 6) displayed a similar acute lethal GVHD, with 100% mortality rate and equivalent survival time (15 +/- 0.7, 16.8 +/- 0.9, and 16 +/- 0.6 days, respectively) (P greater than 0.01). On the other hand, 80% of the recipients of a segmental jejunal graft (N = 10) recovered from a transitory form of GVHD and regained weight similarly to the isografted rats (N = 4). It was concluded that the entire small bowel, jejunum, and ileum can provoke an equivalent GVHD after transplantation, whereas a segment of jejunum decreases the intensity of GVHD, probably by reducing the amount of transplanted lymphoid tissue. PMID- 2255253 TI - Cervical small bowel transplantation in the rat: a useful tool. AB - Orthotopic intestinal transplantation in the rat is highly successful, but circumstances may require an extraabdominal graft location. We describe a microsurgical technique for cervical intestinal transplantation in the rat, which has been used to investigate the immune status of hosts already bearing an intraabdominal bowel transplant. A 10 cm segment of donor jejunum is harvested on a pedicle of superior mesenteric artery and superior mesenteric vein. In the recipient, the carotid artery (CA) and external jugular vein (EJV) are isolated. The venous anastomosis is performed end to end to the medial EJV branch, and the arterial anastomosis is completed end to side to the CA. Both anastomoses are performed with interrupted 10-0 nylon. The bowel is placed in a subcutaneous pocket in the neck, with both ends exteriorized. The procedure was performed in 11 donor-recipient pairs planned to elicit rejection, graft-vs.-host disease (GVHD) or graft acceptance. No technical complications were encountered. All rats survived long term, and their grafts were monitored histologically. The expected immune responses were observed, but rejection and GVHD were not fatal to the host with this model. We conclude that this technique is feasible and reliable to monitor the progress of isolated intestinal transplants. The location in the neck does not disrupt normal intestinal function of the recipient and may have multiple applications in the study of intestinal transplant immunology and physiology. PMID- 2255254 TI - International issues: an emerging trend. PMID- 2255255 TI - Presidential address 1990. Mental retardation at the close of the 20th century: a new realism. PMID- 2255256 TI - Costs of providing residential and related support services to individuals with mental retardation. AB - The per diem costs of providing residential services for persons with mental retardation in group homes, family homes, and apartments in the Macomb-Oakland Region of Michigan and in Region V in eastern Nebraska were found to vary far more by type of living arrangement than by resident level of need. Nearly all of the variation in the per diem costs of staffed, as opposed to family-operated, living arrangements could be explained in terms of staff-to-resident ratios and staff compensation levels. PMID- 2255257 TI - Normalization and integration: a look at the Swedish experience. AB - Quality service provision is seen as an integral and essential element of the normalization effort in Sweden. Results of the present study suggest that Sweden's well-developed system of comprehensive services and support for individuals with mental retardation ensures a level of security and material well being that allows these people to live and function within society-at-large. Considered in relation to Nirje's (1980) elaboration of integration as it pertains to normalizing the life conditions of persons with mental retardation, functional and physical integration are clearly evident in many community settings. At the same time, other indicators of integration, such as social relations and association with people without mental retardation, suggest that social integration continues to challenge the community living endeavors in Sweden in much the same way as it does in North America. PMID- 2255258 TI - Characteristics of users and nonusers of respite care. AB - Characteristics of users and nonusers of respite care services were investigated in a sample of 105 biological mothers of children evidencing mild/moderate or severe/profound disabilities. Analyses revealed a low level of service use across groups and no significant difference between groups, despite significantly higher levels of reported stress among mothers of children with more severe disabilities. Results also indicated that marital status and the child's level of functioning were related to reported levels of depression, social support, and personal well being. The discrepancy between demonstrated need and service utilization was highlighted in the discussion. PMID- 2255259 TI - Transition of persons with developmental disability from extended sheltered employment to competitive employment. AB - The proposition was tested that persons with developmental disabilities randomly assigned to a supported work program would obtain more employment in the competitive labor market than would a randomly assigned group of control subjects receiving conventional workshop services. A measure of association (chi-square) conducted between the two groups and three categories of work showed that the experimental group obtained significantly more employment. PMID- 2255260 TI - Validity of self-report of adaptive behavior skills by adults with mental retardation. AB - The validity of self-reports of 48 adults with mental retardation of daily living competency using the recently revised Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984) was investigated. Self-report was compared to standard Vineland interviews of subjects' program counselors and to demonstrated competency in a real-life setting. On domains measuring adaptive skills, the subject and counselor interviews yielded highly consistent results. On the optional Maladaptive Behavior domain, however, the subjects with mental retardation underreported problematic behavior. Response validity and implications for use of self-report for program planning and placement decisions were discussed. PMID- 2255261 TI - An "adaptive behavior" ambiguity. PMID- 2255262 TI - Effect of calcium pidolate on biochemical and hormonal parameters in involutional osteoporosis. AB - The purpose of this study was to determine the value of calcium pidolate in the treatment of involutional osteoporosis. This compound has been reported to be better absorbed than other calcium salts, to lower the levels of parathyroid hormone (PTH) and to raise those of growth hormone (GH). We accordingly treated one group of 10 women suffering from involutional osteoporosis with the equivalent of 1 g elemental calcium and administered a placebo to a second group of 10 osteoporotic women whose mean age and body surface area were comparable. Basal sequential multiple analysis (SMA-12) was performed in all subjects to determine calcium, phosphorus, alkaline phosphatase (ALP) and total protein levels, the same blood samples being used for the evaluation of mean PTH, GH and osteocalcin (BGP). Urinary 24-h calcium excretion was determined and the calcium/creatinine (Ca/Cr) and hydroxyproline/Cr (HP/Cr) ratios were measured in 12-h fasting urine samples, the results being corrected for glomerular filtrate. The same parameters were measured again following a month of uninterrupted treatment. After 30 days, we observed no differences in either group as regards calcaemia, phosphataemia, ALP, total proteins, PTH, GH, BGP or 24-hour calciuria. The only noteworthy changes seen were significant decreases (P less than 0.001) in the Ca/Cr and HP/Cr ratios in the group treated with calcium pidolate. These results show that calcium pidolate at the dose administered inhibits bone resorption but does not affect the levels of PTH, GH, BGP or ALP in the medium term. Our findings indicate that it has no influence on bone formation. PMID- 2255263 TI - Effect of oral oestriol on vaginal flora and cytology and urogenital symptoms in the post-menopause. AB - The effect of oral oestriol (3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks) on the vaginal bacterial flora, vaginal cytology and urogenital symptoms was assessed in a double-blind, placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome. No significant differences were observed with regard to the occurrence or severity of urogenital symptoms, vaginal pH, karyopyknotic index (KPI) or the baseline results of vaginal bacterial cultures in the 18 patients (mean age 71.6 +/- 1.0 years) treated with oestriol and the 17 women (mean age 72.6 +/- 1.4 years) who received placebo tablets. A decrease in both vaginal pH (P less than 0.001) and the proportion of faecal-type bacteria (P less than 0.05), and an increase in the KPI (P less than 0.01) and the proportion of lactobacilli (P less than 0.001) were recorded after 10 weeks of treatment with oral oestriol. At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels. In the patients treated with placebo no significant changes occurred in vaginal pH, KPI or the proportion of lactobacilli in vaginal cultures during the course of this study. Urogenital symptoms improved in both groups after medication (and even after the medication-free period) in relation to the baseline assessment, which reflects the latter's subjective nature. PMID- 2255264 TI - Plasma lipid and lipoprotein levels in obese post-menopausal women: effects of a short-term low-protein diet and exercise. AB - Obesity is associated with an increased prevalence of cardiovascular and cerebrovascular disease, probably mediated by the induction of an atherogenic lipid profile. Since few data are available concerning plasma lipid levels and the effects of short-term dieting on these parameters in obese postmenopausal women, we studied plasma lipid and lipoprotein levels in such women and also the effects on these levels of a short-term hypocaloric low-fat diet combined with a moderately intense physical exercise programme. Plasma triglycerides and low density-lipoprotein cholesterol (LDL-C) levels were significantly higher, whereas high-density-lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) levels, as well as the HDL-C/LDL-C and ApoA1/ApoB ratios, were significantly lower in moderately to severely obese women (Body Mass Index greater than 30, n = 26) than in non-obese post-menopausal controls. A short-term (4 week) protein-sparing modified fast diet, providing 400 calories (1675 J), resulted in a mean weight loss of 7.7 +/- 2.8 (S.D.) kg. While plasma cholesterol, LDL-C and ApoB levels decreased by approximately 25% and reached the levels recorded in normal controls, ApoA2 decreased by 20%. HDL-C and HDL2-C levels remained unchanged and as a consequence the HDL-C/LDL-C and the ApoA1/Apob ratios increased, indicating a shift towards a less atherogenic lipid profile. No correlation was observed between weight loss and changes in lipid or lipoprotein levels. It was concluded that a hypocaloric, low-fat diet combined with our physical exercise programme, resulted in the normalization of plasma lipids within 4 weeks. PMID- 2255265 TI - Serum placental protein 14 in pre-menopausal and post-menopausal women- dependency on oestrogen/progestogen status. AB - In view of the increasing use of oestrogen-progestogen therapy in post-menopausal women the availability of possible biochemical marker of endometrial response to progestogen would be highly desirable. Placental protein 14 (PP14) has recently been shown to be excreted from the endometrium during the secretory phase of the menstrual cycle. In the present study we examined the concentration of serum PP14 (S-PP14) in 15 pre-menopausal women during the menstrual cycle and in 30 early post-menopausal women receiving three different doses of 17 beta-oestradiol (E2), cyclically combined with norethisterone acetate (NETA). S-PP14 levels peaked on day 1 following the onset of menstrual bleeding and on day 7 during NETA administration. It was possible to estimate the area under the S-PP14 curve reliably from one or two blood samples taken at optimal times. In the post menopausal women, S-PP14 varied in a highly significant dose-dependent manner, i.e., the higher the E2 dose (in relation to the fixed NETA dose) the higher the S-PP14 response was found to be. We suggest that S-PP14 measurements might reflect the quantitative development of the endometrium in the secretory phase in both pre-menopausal and post-menopausal women. PMID- 2255267 TI - Human carcinogenesis: a disciplinary perspective. AB - With the emergence of significant national efforts to comprehend and control the human cancers during the early 1970's, the existing biomedical disciplines of cellular pathology, virology and immunology seemed destined to play a central role in these efforts. Since that time, however, new biomedical disciplines, e.g., molecular toxicology, molecular epidemiology and molecular pathology/genetics, have emerged. Integration of the knowledge embraced by these disciplines provides a view of human cancer from natural historical perspectives embracing the causal chain, a view relevant to national priorities and policies in approaching cancer comprehension and control. PMID- 2255266 TI - Sequential use of norethisterone and natural progesterone in pre-menopausal bleeding disorders. AB - Sequential treatment with norethisterone (NET) or natural micronized progesterone (NMP) was administered randomly to 80 consecutive patients attending our clinic because of cycle disorders. The endometrial morphology indicated a need for progestogen therapy in all cases and the endometrium was hyperplastic in half of the women before therapy. Hyperplastic changes disappeared during the first three cycles of treatment with both NET and NMP, the duration of treatment being 6 months. However, the carry-over effect of both progestogens was short: three months after treatment was discontinued a proliferative or hyperplastic endometrial pattern recurred in 24% and 10% of cases, respectively. Whereas NET decreased oestradiol, follicle-stimulating hormone, luteinizing hormone and sex hormone-binding globulin levels (P less than 0.001) no changes were seen during NMP treatment. High-density-lipoprotein cholesterol and triglyceride levels were also lowered by NET (P less than 0.001-0.02) and there was a slight decrease in phospholipids. NMP treatment induced no changes in serum lipid values and thus offers an alternative form of therapy in premenopausal bleeding disorders. PMID- 2255268 TI - Herpes gestationis--bullae from hormones that cause increased extracellular matrix (autoantibodies to epidermal basement membrane as a secondary phenomenon). AB - Herpes gestationis is a bullous skin disease clearly secondary to the hormones of pregnancy and other hormonal influences. It is the result multiple hormones. No one hormone is specific. The hormones increase ground substance viscosity in the skin and this induces edema and bullae formation. Only 10 to 20% of the patients demonstrate IgG formation by indirect immunofluorescence. By direct immunofluorescent studies 30 to 40% of the patients demonstrate deposition of IgG in the basement membrane zone. Other variations of immune factors are present in most cases but they are weak by titers usually present in most so called autoimmune disorders. Many bullous diseases of the skin, including herpes gestationis, are considered autoimmune. It is known that trauma to cells and tissues can induce autoantibodies to form. It is proposed that autoantibodies can form as a secondary phenomenon in bullous skin disorders. The authors who have proposed an autoimmune etiology of herpes gestationis do not attempt to explain the clear association of the disease with the hormones of pregnancy, other female hormones, chorio-carcinoma, or hydatidiform mole. PMID- 2255269 TI - High viscosity of newborn extracellular matrix is the etiology of erythema toxicum neonatorum: neonatal jaundice?: hyaline membrane disease? AB - At the time of birth, the fetal ground substance is under the influence of maternal and placental hormones. Hormones are known to exert significant effect on ground substance. The ground substance viscosity that is ideal for intrauterine life is too viscous for the newborn. Sites of minor skin trauma develop swelling, inflammation and pustules. Dilution of tissue fluids causes formation of some of the mediators of inflammation including those responsible for intraepidermal pustule formation. The newborn responds to inflammation with eosinophilic granulocyte. The clinical lesions referred to as erythema toxicum neonatorum are known to localize at pressure sites. The skin lesions correct as maternal and placental hormone influence weakens. The entity occurs in 31 to 72% of white infants. The hormone induced viscosity changes may aid in better understanding some aspects of neonatal physiology; such as jaundice of the neonatal period, the eosinophilic granulocyte inflammatory response of the neonatal period and hyaline membrane disease. PMID- 2255270 TI - Anorexia nervosa: search for biological relevance. AB - Anorexia nervosa was explored as the possible expression of an aberration of the processing of information which ordinarily has value in life protection or extension. Each of 6 areas was briefly reviewed, and noted to have the potential for failure to balance 2 or more factors. Anorexia nervosa may prove to be a psychiatric disorder in which there is altered handling of signals which otherwise are useful in survival/longevity. PMID- 2255271 TI - The role of caffeinated beverages in dental fluorosis. AB - Recent studies have demonstrated that the incidence of dental fluorosis has increased during the past decade. Greater availability and use of fluoride containing gels, mouth rinses, dentifrices, etc., improper prescribing of fluoride supplements and ingestion of fluoride dentifrice by some children are some of the suggested determinants of dental fluorosis. However, based on the increase in consumption of tea, coffee, and other caffeine-containing beverages by the children, and the augmentative effect of caffeine on fluoride bioavailability, we theorize that the rise in incidence of dental fluorosis in North America is mainly due to the replacement of water intake by caffeine containing beverages among the young population. PMID- 2255272 TI - The etiology of multiple sclerosis: a new and extended vascular-ischemic model. AB - It is hypothesized that multiple sclerosis is a disease of the cerebro-vascular system. The basic defect is visualized as a wound in the CNS due to a focal hypertension of genetically susceptible vessels which results in vascular injury and the initiation of a series of biochemical and physiological events culminating in an ischemic hypoxia leading to demyelination and a secondary damaging process associated with the immune system. PMID- 2255273 TI - The spasm of resistance vessel concept of ischemic heart disease and other ischemic diseases. AB - This communication will discuss the spasm of resistance vessel concept of ischemic heart disease and other ischemic diseases, and will focus on ischemic heart disease. The hypothesis is regarded as a separate model or paradigm, and is based on the principle that spasm of resistance vessels directly induces symptoms in these conditions. Resistance vessels help maintain vascular homeostasis through autoregulatory mechanisms, and spasm of resistance vessels is considered to represent 'inappropriate' activation of these mechanisms by disease states, which are equated with risk factors. For ischemic heart disease, the most important risk factor is stenotic coronary artery disease, and the concept asserts that severe ischemia secondary to coronary artery disease causes sufficient tissue injury to incite injury-spasm of resistance vessels. While it is universally accepted that occlusions of epicardial arteries by stenotic coronary artery disease, spasm, and thromboses directly induce clinical symptoms, the hypothesis suggests that these occlusions have other roles. The concept accepts all current treatments of ischemic heart disease, but as this disorder is viewed differently, a significantly different direction of research is proposed for improving its treatment and prevention. PMID- 2255274 TI - Multiple sclerosis--one manifestation of neurobrucellosis? AB - There is good geographic evidence that an environmental factor is implicated in the aetiology of multiple sclerosis (MS). Controversy surrounds the interpretation of many studies supporting notions on whether the disease has greater prevalence in urban or rural communities. Rather than focus on residence at birth, in teenage years or at the time of study, analyses of MS mortality by occupation and a case control study to define exposure to animal farm products is thought to shed light in this controversy. The conclusion reached from the results of these studies is that exposure to farm animals or raw products is a common denominator in the aetiology of MS. A literature search for references of zoonotic disease with neurological symptoms produced a range of papers on brucellosis. A study of the literature on neurobrucellosis supports the hypothesis on clinical grounds. Finally, blood serum studies of Brucella exposure in a series of MS subjects and controls is described. These epidemiological studies support the hypothesis, that central nervous system involvement from exposure to brucellosis, may present with the features of multiple sclerosis. PMID- 2255275 TI - An evolutionary perspective of endotoxin: a signal for a well-adapted defense system. AB - In the evolutionary view of endotoxin presented here, endotoxin is the primary signal animals use to detect gram negative (Gr-) bacteria. Since endotoxin, or lipopolysaccharide (LPS), is an integral part of the surface of all Gr- bacteria, it was excellent evolutionary 'choice' for the signal. The concept of an 'endotoxin response system' (ERS) is introduced. The ERS protects against Gr- bacteria by employing many of the body's defenses to both detect and react against LPS. The intensity of the response has evolved to maximize protection while minimizing the biological cost and self-damaging effects. The setting of the response, here termed the 'endostat', is programmed by natural selection and fine tuned by feedback mechanisms. Other potentially invasive organisms are detected by different signals, but the effector components of the defenses are similar. This evolutionary view of LPS offers a framework for the seemingly contradictory findings on endotoxin and suggests new avenues of productive research. PMID- 2255276 TI - On the coagulation of the blood: an elaboration of Lord Lister's hypothesis and the four-factor model of Morawitz. AB - It is postulated that ADP secreted by platelets is the physiological thromboplastin which initiates the conversion of prothrombin to thrombin and hence brings about the coagulation of the blood. The experiments which led to the formulation of the hypothesis are described. Experimental work compatible with the hypothesis is outlined. The implications of the hypothesis with regard to the modern cascade theory of coagulation are discussed. PMID- 2255278 TI - The role of pulmonary hypertension in the pathogenesis of bronchial asthma. AB - In patients with bronchial asthma, when blood pressure in the pulmonary artery is measured, very often hypertension is registered. This pulmonary hypertension is not secondary to hypoventilation, as in patients with chronic bronchitis or pulmonary emphysema, since patients with bronchial asthma are hyperventilating. The pulmonary hypertension in them must be therefore classified as primary. It is probable that its origin is in an allergic vasoconstriction of the pulmonary artery, occurring simultaneously with the well known bronchoconstriction. PMID- 2255277 TI - Is hexachlorobenzene human overload related to porphyria cutanea tarda? A speculative hypothesis. AB - After the epidemic outbreak of Porphyria Turcica from 1955 to 1961, the porphyrinogenic effect of hexachlorobenzene (HCB) on humans and animals has been fully confirmed. HCB is an environmental contaminant originated from its use as fungicide or obtained as a by product from industrial residues. Measurement of HCB levels in adipose tissue and maternal milk is a useful tool for monitoring its body stores which are clearly higher in Spain than in other European or American countries. At least in the Spanish area of Catalunya, the HCB fat tissue concentration decreased from more than 5 ppm in 1981-1982 to less than 3 ppm in 1986-1987. Porphyria cutanea tarda is a relatively frequent disease in Spain. More than 700 cases were observed in Madrid from 1964 to 1988. Before 1970, less than 10 cases were annually detected, a figure that rose up to 60-70 annual cases from 1977 to 1982 and decreased to less than 25 annual cases from 1985 to 1988. Based on all these previous data, a speculation is tempting: the high and variable incidence of porphyria cutanea tarda in Spain may be related to environmental contamination with HCB. PMID- 2255279 TI - MRSA--is control worthwhile and feasible? PMID- 2255280 TI - Fibrositis/fibromyalgia syndrome: the key to the puzzle of chronic pain. PMID- 2255281 TI - Trends in prescribing--the dawn of DUSC. PMID- 2255282 TI - The epidemiology of invasive Haemophilus influenzae infections in children under five years of age in the Northern Territory: a three-year study. AB - A survey of all episodes of invasive Haemophilus influenzae infections that were diagnosed over a three-year period in children seen at the regional hospitals of the Northern Territory has found a significantly (P less than 0.001) higher incidence in children in Central Australia (the Alice Springs and Barkly regions, and the Anangu Pitjantjatjara Lands) than in the Top End (the Darwin, East Arnhem and Katherine regions), and a greater incidence in Aboriginal than in non Aboriginal children. Identified risk factors for Aboriginal children were infancy (more than 70% of cases occurred before 12 months of age), sex (with a predominance in girls) and residence in Central Australia; the estimated annual incidence for Central Australian Aboriginal children was 991 cases per 100,000 children. There was a significant correlation (r = 0.62) between the total number of cases diagnosed each month in Central Australia and the mean monthly temperatures recorded in Alice Springs. Whereas virtually all cases of invasive H. influenzae infection in non-Aboriginal children were caused by type b strains, strains other than type b caused 15% of the cases in Aboriginal children. The possibilities for prevention by immunization are discussed. PMID- 2255283 TI - Successful control of endemic MRSA in a cardiothoracic surgical unit. AB - After a substantial increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the Cardiothoracic Surgical Unit at St. Vincent's Hospital, Sydney, a prospective study was undertaken in early 1986 to ascertain the carrier status of all patients entering the Unit. Of 84 patients, 27.4% were found to carry MRSA and the perineum was the major site of carriage, with 69.6% of MRSA positive cases carrying the organism in this site. As a result of these findings, the period of perioperative antibiotic cover was shortened, whole-body washing of patients with a 1% triclosan preparation was instituted and routine postoperative perineal swabs were taken. During the 18 months after implementation of these policies, a highly significant reduction in the number of MRSA carriers and infections was observed. The monitoring of perineal colonization proved to be a useful marker for increases in MRSA in the Unit. PMID- 2255284 TI - End-stage renal failure in children: 16 years' experience at one Australian centre. AB - Sixty-five children over one year and under 15 years of age began treatment for end-stage renal failure between 1973 and 1988. Sixty-one renal transplants were performed in 53 children, 39 of these were from living donors (38 were first degree relatives and one was an emotionally related volunteer). Thirteen children, of whom seven had received transplants and six had not, died, including three children with functioning transplants; nine deaths occurred in the first eight years of the programme. Cumulative five-year and 10-year patient survival rates were 78% and 75%, respectively. Eighteen transplants failed, 12 as a result of rejection, five as a result of disease recurrence and one due to primary non function. Cumulative five-year and 10-year transplant survival rates for first grafts were 66% and 53%, respectively. For living donor transplants these rates were 85% and 68%, respectively. Growth rates fell by 0.4 +/- 0.05 standard deviation score (SDS) per year in children undergoing dialysis, were normal in children with renal transplants receiving prednisone (change in SDS per year, 0.02 +/- 0.08) and increased by 0.36 +/- 0.07 SDS per year in children with transplants receiving cyclosporin A alone. Currently, 32 (82%) of 39 transplant recipients and 7 (58%) of 12 patients undergoing dialysis attend school or work full time. Although both dialysis and transplantation are acceptable therapies for children with end-stage renal failure, successful transplantation provides the best opportunity for satisfactory growth and development. PMID- 2255285 TI - Non-surgical mitral valvotomy. AB - Percutaneous transseptal mitral valvotomy was performed on 14 occasions in 13 patients; in one patient, the procedure was unsuccessful at the first attempt, but was repeated successfully. All other attempts were successful, giving a procedure success rate of 93% and a patient success rate of 100%. The only complication was transient diplopia in one patient, presumably due to a small cerebral embolus. This early experience confirms that this procedure is easily learnt, and can be performed with good results and low risk in selected patients with mitral stenosis. PMID- 2255287 TI - Manifestations and management of paraquat poisoning. PMID- 2255286 TI - Age and time trends in the prevalence of cervical intraepithelial neoplasia on Papanicolaou smear tests, 1970-1988. AB - Substantial increases in the prevalence of cervical intraepithelial neoplasia (CIN) in women of all age groups are apparent from Papanicolaou smear test reports issued by the Victorian Cytology (Gynaecological) Service between 1970 and 1988. Most of the change in prevalence is due to an increase in reports of neoplasia of a lesser severity than CIN III. A progressive lowering of the age group having the highest prevalence of "definite" CIN is evident, from women aged 40-49 years in 1970-1973 to women aged 25-29 years in 1982-1988. The prevalence of "possible" CIN has consistently been highest among the youngest age groups screened. While 6.7% of screened women from the age group 20-24 years received a report of "definite" or "possible" CIN in 1988, only 0.08% of women in this group received a report of CIN III. Cohort analysis revealed that for women born between 1949 and 1958, the prevalence of CIN III continued to increase during 1988. PMID- 2255288 TI - Differentiation of Becker muscular dystrophy from limb-girdle muscular dystrophy and Kugelberg-Welander disease using a cDNA probe. AB - A 31-year-old man previously investigated for a neuromuscular disorder was diagnosed as having either limb-girdle dystrophy, spinal muscular atrophy, or Becker muscular dystrophy. Extensive clinical and special neurological investigations failed to clarify this differential diagnosis. However, recent DNA studies have shown a deletion of the dystrophin gene, thereby providing an unequivocal diagnosis of Becker muscular dystrophy. The application of molecular genetic techniques in the diagnosis of inherited neuromuscular disorders is discussed. PMID- 2255290 TI - Elbow angle and blood pressure readings. PMID- 2255289 TI - Psychological distress among volunteer AIDS counsellors. PMID- 2255291 TI - Enteric pathogens in mentally handicapped patients in hospital. PMID- 2255292 TI - False positive reactions in a salt-aesculin test for Enterococcus spp. PMID- 2255293 TI - Reduction of selected forearm fractures in the emergency department. PMID- 2255294 TI - Anticonvulsant agents and osteomalacia. PMID- 2255295 TI - Yersinia enterocolitica bacteraemia after blood transfusion. PMID- 2255296 TI - Intracavernous injections for impotence. PMID- 2255297 TI - Rabies vaccine. PMID- 2255298 TI - Retraction. Parkinsonism: a clinical marker of exposure to neurotoxins. PMID- 2255299 TI - Prenatal methylmercury exposure results in dendritic spine dysgenesis in rats. AB - To test the prenatal neurotoxic effect of low doses of methylmercury chloride (MM), the toxic agent was given by gavage to pregnant Wistar rats on days 6 to 9 after conception in doses of 0.025, 0.05, 0.5 and 5.0 mg/kg/day. The offspring of these animals were subjected to a routine developmental and behavioral testing battery. In essence, functional changes including impaired swimming behavior, increased auditory startle amplitude, increased passiveness and increased locomotor stereotypy compared to controls were the result of prenatal MM exposure, tested from the second to the seventh month postnatally. Further, in each group, ten prenatally treated rats were investigated histopathologically at the age of twelve months. The most striking effect was a distinct difference in the morphology of the dendritic spines of the pyramidal neurons in the somatosensory cortex demonstrated by Golgi impregnation. The spine abnormalities in the experimental animals consisted of a reduction of stubby and mushroom shaped spines and a predominance of long and tortuous spines. Dendritic spine dysgenesis implies defective development and might be the pathological feature of the impaired behavior and learning of the MM-exposed animals. PMID- 2255300 TI - Proceedings of the second meeting of the International Neurotoxicology Association. Sitges, Spain, May 22-26, 1989. Proceedings. PMID- 2255301 TI - Neurotoxicity of organic solvent mixtures: embryotoxicity and fetotoxicity. AB - The toxicity of organic solvents at different concentrations was examined to determine their effect on pregnant rats and their offspring. A very serious effect which inhalational exposure to n-hexane, methyl-ethyl-ketone and a mixture of the two organic solvents produced in pregnant rats was a concentration dependent increase of intrauterine mortality. In cases of only prenatal exposure, the persistence of reduced body growth was an important result obtained at all concentrations we investigated (first solvent experiment, 500 ppm; second solvent experiment, 800 ppm; and third solvent experiment, 1000 to 1500 ppm; 23 hr day). In these cases, a delay in the maturation of cerebellar cortex was also observed. In cases of pre- and postnatal solvent exposure, the effects of malnutrition were added to the solvent-induced retardation. This resulted in an extreme delay in tissue maturation accompanied by a retarded cell maturation. The solvents examined had no teratogenic effect in pregnant rodents and their offspring. Neurotoxicity was restricted to the known structures of the adult animals, whose axons were damaged. They did, however, show a concentration-dependent embryotoxic and fetotoxic effect. PMID- 2255302 TI - Differential effect of carbon tetrachloride on the cell membranes of neurons and astrocytes. AB - Primary cultures of neurons and astrocytes from chick embryos were used to study the effect of CCl4 on the plasma membranes. The cultures were exposed to 0, 1, 2, 3 or 4 mM CCl4 in a closed chamber system for 30 or 60 minutes. The effects of the exposure were examined by means of scanning electron microscopy and by measuring the degree of lipid peroxidation. In neuron cultures the presence of 1 mM CCl4 for 60 min caused holes in the plasma membranes and led to a swelling of the cell bodies. At 4 mM CCl4 the membranes were totally destroyed, leaving cytoskeletal elements visible. In astrocyte cultures, on the other hand, no effects up to 2 mM were observed. At 4 mM some cells had rounded up, but the membranes were still intact. These data correspond very well with the results that neurons, in contrast to astrocytes, show a concentration-dependent increase in lipid peroxidation. The results from this study may indicate that the mechanism of action of CCl4 is different in neurons and astrocytes. PMID- 2255303 TI - Hen liver and plasma can metabolize hexyl-DCP phosphoramidate at a rate comparable to that of rat. AB - The in vitro and in vivo biochemical properties of O-hexyl, O-dichlorophenyl phosphoramidate (hexyl-DCP) as inhibitor of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) were studied, as well as their neurotoxic effects. The differences found were suggested to be due to biotransformation effects. In this work, the in vitro time-dependent degradation of hexyl-DCP by plasma, liver and brain homogenates of rat and hen at 37 degrees C at pH 7.4 are studied using 100 nM initial concentration. The loss of inhibitory potency against AChE was used as sensor of the biodegradation rate. An approximate estimation of the residual compound was made by comparison with an inhibition calibration curve. The rate of enzymatic degradation was corrected for the spontaneous hydrolysis. Rat tissues showed some higher activities (24, 17, 1 mU/g for plasma, liver, and brain, respectively) than hen (17, 6, 1 mU/g), with activities being highest for plasma and lowest for brain. Hexyl-DCP is a chiral compound. The loss of anti-AChE power could be due to degradation of only one of the two stereoisomers. PMID- 2255304 TI - Effects of lipoic acid in hexacarbon-induced neuropathy. AB - The effects of lipoic acid on hexacarbon neurotoxicity in rats were investigated. Rats were exposed by inhalation to n-hexane for 24 hours/day, 7 days/week, up to a total period of 9 weeks. Eight animals were exposed to 700 ppm n-hexane only, and eight animals were exposed to 700 ppm n-hexane and additionally received 100 mumol/kg lipoic acid PO daily. Clinical status of the animals was evaluated by examination of general condition, motor performance tests and neurophysiological measurements of caudal nerve motor conduction velocity. Results showed that animals exposed to 700 ppm n-hexane developed severe motor neuropathy leading to paralysis by the 6th week. Motor distal latencies of these animals were severely prolonged. In contrast, in animals treated with lipoic acid the onset of motor neuropathy was delayed for approximately 3 weeks as could be demonstrated by motor performance tests and measurements of motor distal latencies. PMID- 2255305 TI - Reduced conduction function in central nervous system by 2,5-hexanedione. AB - In order to examine the involvement of the central nervous system (CNS) following administration of 2,5-hexanedione (2,5-HD) in rats, the present experiment was conducted using the auditory brainstem response (ABR) and somatosensory-evoked potentials (SEPs). Nine male Wistar rats were given 2,5-HD subcutaneously at 350 mg/kg/day, five days a week for three weeks. For the control group, nine male rats were employed. One week after the last administration, ABRs were measured from the scalp with subcutaneous needle electrodes under pentobarbital anesthesia. Click sounds of 61 and 86 dB sound pressure level were used in ABR measurement (61dB-ABR and 86dB-ABR, respectively). The SEP evoked by stimulation at the forepaw and the medulla oblongata (SEP and SEP-M) were recorded from the surface of the cerebral cortex using screw electrodes under immobilization. The significant findings observed in 2,5-HD-treated rats included: 1) delayed latencies of the Ist, IIIrd, IVth and Vth components of the 61dB-ABR and the Ist, IInd, IIIrd and Vth components of the 86dB-ABR; 2) increased interpeak latencies (IPLs) between III-V and I-V of the 61dB-ABR; 3) delayed latencies of the P1 and N1 components of the SEP and the N1 component of the SEP-M. The delays of IPL-III V of the 61dB-ABR and the N1 component of the SEP-M were considered to reflect conduction disorders of the auditory and somatosensory afferent pathway in the CNS, respectively. Thus, the ABR may be a sensitive method to detect disorders in the CNS produced by neurotoxic substances. PMID- 2255306 TI - Temperature dependence of the toxic effects of phenytoin on peripheral neuromuscular function of the rat tail. AB - We studied the acute effects of a single dose of phenytoin (250 mg/kg) on peripheral neuromuscular function. The evoked muscle action potentials of the dorsal segmental muscles in the rat tail, and the conduction velocity of the dorsal nerve trunk which innervates them, were measured before and after the intraperitoneal injection of phenytoin. The experiments were performed at different temperatures, 27 (physiological tail temperature), 36 and 37 degrees C (physiological central temperature) in different groups of animals. The amplitudes of the evoked muscle action potentials in the treated groups showed no significant modifications at 27 degrees C, at 36 degrees C a small nonsignificant decrease could be observed, and a complete block occurred at 37 degrees C. The mean blocking time was approximately one hour. No significant variations of conduction velocity were observed at 27 and 36 degrees C, whereas it decreased significantly after 30 minutes at 37 degrees C. The results presented confirm phenytoin toxicity. How far these results, especially the decrease of nerve conduction velocity observed at 37 degrees C, confirm a previous hypothesis which supported that peripheral and central nervous system are affected by phenytoin by similar mechanisms, is discussed. PMID- 2255307 TI - The effect of acute trichloroethylene exposure on electroretinogram components. AB - The effects of acute exposure to trichloroethylene (TCE) on the electroretinogram (ERG) and oscillatory potentials (OPs) were studied on adult New Zealand rabbits anesthetized with urethane. The ERG and OPs were recorded under photopic conditions with a speculum electrode, with pupils fully dilated and the cornea anesthetized. Emulsified (Intralipid) TCE was given intravenously in three consecutive injections of equal volume for a total dose varying between 24 and 85 mg/kg. Averaged ERG and OPs (50 sweeps) were taken up to 250 minutes after the last TCE injection. Our results indicated that, irrespective of the dose used, there was a significant (p less than 0.001) reduction (average: 50%) in the amplitude of the b-wave of the ERG following TCE injection. In contrast, the OPs showed a differential effect. At low doses, OP4 showed a significant (p less than 0.001) reduction resulting in some cases to its complete extinction, while at higher dose there is a marked increase in amplitude. Our results would suggest that the OPs are a better retinal potential to assess the level of TCE toxicity than is the b-wave of the ERG. PMID- 2255308 TI - Neurotoxicity testing during long-term studies. AB - Several tests and methods for the investigation of neurotoxicity were performed with female Wistar rats for up to 187 days. The methods were validated by testing 10 rats treated with beta,beta'-iminodipropionitrile (IDPN) and 10 control rats. Cage side observation of the animals revealed signs of altered behavior and motor dysfunction of the IDPN-treated rats. Results of a neuromuscular screen indicated changes in gait, righting reflex, grip strength and performance of the negative geotropism test. Investigation of the animals in activity monitors and on the accelerating rotarod showed changes of several parameters. The motor nerve conduction velocity, measured 6 months after the first treatment, was reduced by 6.7 meters per second in the IDPN group compared to controls. From the results of the tests it can be concluded that the methods chosen can be used during long term studies but may be most useful for animals not older than 12 months. PMID- 2255309 TI - Neurobehavioral and sensory irritant effects of controlled exposure to a complex mixture of volatile organic compounds. AB - Subjective reactions of discomfort, impaired air quality, irritation of mucosal membranes, and impaired memory have been reported in chemically sensitive subjects during exposure to volatile organic compounds (VOCs) found in new buildings. Sixty-six normal healthy male subjects aged 18-39 were exposed for 2.75 hr to a complex VOC mixture at 0 and 25 mg/m3. Each subject completed control and exposure sessions at one-week intervals in counterbalanced order. Measurements included comfort ratings of eye, nose and throat irritation, symptom questionnaire and computerized behavioral tests. Subjects found the odor of VOCs unpleasantly strong and reported that VOC exposure degraded air quality, increased headache and produced general discomfort. VOC exposure did not affect performance on any behavioral tests. PMID- 2255310 TI - Neurobehavioral effects of a long-term exposure to tetraalkyllead. AB - Employees of a factory producing antiknock additives for gasoline were examined psychologically after an exposure of an average of 14 years. A neurobehavioral symptom questionnaire, tests of single and choice reaction time, a cancellation task and a digit symbol test were the neurobehavioral variables. Total lead in urine and trimethyllead in urine showed different patterns of correlation with the neurobehavioral measures. Intellectual abilities (logical reasoning), age, and job years were controlled by partial correlation statistics as possible confounders. Referring to the low level of 21 micrograms lead per 100 ml blood and regarding the dose-response relations reported in the literature, the results support the hypothesis of a special neurotoxicity of the alkyllead compounds. PMID- 2255311 TI - Effects of occupational exposure to organic solvents upon cognitive performance. AB - Twenty-three individuals exposed to mixed organic solvents were compared with 23 nonexposed controls on a number of cognitive performance tasks. Solvent exposure resulted in a significantly poorer performance on the forward digit span test, copying of a complex figure, and on semantic memory tests which also measure individual's ability to integrate linguistic information into cohesive units. These tasks rely heavily upon short-term memory and its integrative operations in higher cognitive function. Acute exposure effect was also observed for the linguistic integrative task. PMID- 2255312 TI - Neurobehavioural effects of industrial mixed solvent exposure in Chinese printing and paint workers. AB - Neurobehavioural symptoms and performance tests were evaluated in a group of 78 workers exposed to mixed organic solvents (printers, paint sprayers and paint production workers) and a referent group of 145 unexposed subjects (nonproduction factory workers and volunteer postal workers). Both groups were administered a structured symptoms questionnaire and eight neurobehavioural tests for psycho motor function, visual and auditory memory. An excess of symptoms of fatigue, irritability, depression, poor memory, sleep disturbances and symptoms suggestive of autonomic dysfunction was found in the exposed group. Neurobehavioural test performance was generally worse, and performance on tests of psycho-motor function (choice reaction test and digit symbol) and auditory memory (digit span and associate learning) was significantly poorer in the exposed group. The findings support the view that apparently healthy and actively employed workers exposed to mixed solvents show neurobehavioural deficits. PMID- 2255313 TI - Neurobehavioral effects of acute styrene exposure in fiberglass boatbuilders. AB - A field investigation of the effects of acute exposure to styrene among fiberglass boatbuilders was performed. Personal samples of styrene in breathing zone air and postshift urinary mandelic acid were collected for 105 workers exposed and not exposed to styrene in 6 fiberglass boatbuilding companies in New England. Three tests from the computerized Neurobehavioral Evaluation System (NES) were performed by the subjects in the morning before exposure to styrene, near midday, and at the end of the work day. Duration of exposure averaged 2.9 years (SD = 4.6), 8-hour TWA styrene exposure averaged 29.9 ppm (SD = 36.2), and urinary mandelic acid averaged 347 mg/g creatinine (SD = 465). Regression analyses indicated a statistically significant relationship between postshift performance on the Symbol-Digit test and both acute styrene exposure and mandelic acid. Other analyses comparing workers exposed to less than 50 ppm and greater than 50 ppm styrene also showed a significant effect on Symbol-Digit performance. All three NES tests showed test-retest correlation coefficients above .80, and ease of use for collection of neurobehavioral data under field conditions was demonstrated. PMID- 2255314 TI - Colour vision loss among disabled workers with neuropsychological impairment. AB - Test performance on a neurobehavioural battery was examined with respect to acquired colour vision loss among patients with a history of neurotoxin exposure. The study group included 14 men and 7 women with clinically diagnosed neuropsychological impairment (mean age: 41.3 +/- 8.1 years; mean educational level: 13.4 +/- 1.4 years). Verbal and visual ability, memory and psychomotor function were assessed with the California Neuropsychological Screening Battery. Colour vision was assessed with the Lanthony D-15 desaturated colour arrangement panel. Acquired dyschromatopsia was present in 17 patients (80.9%), 11 of whom manifested patterns of Type II colour vision loss. Simple regression analysis of neuropsychological test performance with respect to colour vision loss, using age adjusted Z-scores, revealed significant relationships (p less than or equal to 0.05) solely for tests which rely heavily on the visual system. Significant differences in visual task test scores were also observed with the type of dyschromatopsia (Kruskal-Wallis, p less than or equal to 0.05). These findings suggest that poor performance on visual tasks and colour vision loss may both result from damage to neuro-ophthalmic pathways or that loss of integrity of the peripheral visual pathways may affect visual task performance. The authors propose that visual testing should be incorporated into neurobehavioural test batteries. PMID- 2255315 TI - Psychological test performance in foundry workers exposed to low levels of manganese. AB - A sample of 30 manganese-exposed foundry workers from two Swedish plants were examined with a partly computerized psychological test battery, comprised of 10 performance tests. Performance of the manganese-exposed workers was compared to that of a matched control group of 60 workers. Matching criteria were age, geographical area, type of work, and the results on a test of verbal comprehension. Performance of the exposed workers was inferior to that of the control group on tests of simple reaction time, digit span, and finger tapping. No correlations were found between performance and the present manganese exposure levels or the number of years employed in manganese work. The results seem to indicate that the present exposure standards for manganese, in Sweden 2.5 mg/m3 and in most other countries 5 mg/m3, are not sufficient to protect workers from negative effects on performance capacity. PMID- 2255317 TI - [The role of the plasmid in expression of the OF-type antigen of group A streptococcus]. AB - In our previous investigations we demonstrated the ability of some natural MLS plasmids to regulate the expression of several functionally related genes of Streptococcus pyogenes. In the present paper the mechanism of the plasmid effect of the SOR expression has been studied. The filter mating transfer of the plasmid pEL1 and pAM beta 1 into the recipient strain 154(8-3)SOR+ (cured of EmR) but not into the strain CSLL2SOR+ resulted in two types of transconjugants obtained: EmRSOR+ (90%) and EmRSOR- (10%). It was found in DNA-DNA hybridization experiments that the OF-EmR transconjugants but not OF+EmR ones carry the same pEL1 plasmids that are harboured by the donor strain SM60ERL1. Mutation to SOR- is considered to be the results of the plasmid of transposon DNA insertion into the homologous region of the recipient strain 154(8-3). PMID- 2255316 TI - Neurotoxic substances also posing a cancer risk: a warning. AB - A large proportion of compounds studied for their neurotoxic potential are at the same time suspected or proven carcinogens. This is demonstrated using the International Neurotoxicology Association (INA) Professional Interest Directory and publications from the field of neurotoxicology as examples. In addition to listing these compounds, the classification scheme used by the International Agency for Research on Cancer (IARC), the Commission of the European Communities (EC), the U.S. Environmental Protection Agency (EPA), the German MAK-Commission of the Deutsche Forschungsgemeinschaft (DGF) and the U.S. National Institute of Occupational Safety and Health (NIOSH) to make qualitative risk assessments is explained. Finally, a short initiation to quantitative risk assessment as performed by the US EPA and the World Health Organization (WHO) is given in order to put the reader into a position as to assess the cancer risk incurred by his/her co-workers and by himself. PMID- 2255319 TI - Genetic toxicology testing and biomonitoring of environmental or occupational exposure. PMID- 2255318 TI - [What are toxins to microbes? (the role of toxins in bacterial ecology)]. AB - The author attempts to answer two questions: whether the toxins, in particular the toxins having their specificity connected with enzymatic activity, are needed for microbial cell physiology and their significance for bacteria that are not the obligate parasites for warm blooded animals. The analysis of literary data supposes the toxins to be essential cellular metabolites since many of them participate in energy acquiring. Besides that a number of toxins is shown to be relevant to microbial life and to affect the micropredators, especially the monocellular organisms feeding the microbes. In connection with the above mentioned, special attention is paid to extrachromosomal location of many toxins genes relating them to bacteriocins. The possibility is not excluded that in the future the new toxins might come to be found having the enzymatic activities. PMID- 2255320 TI - Mutagenicity of vinyl chloride in man: comparison of chromosome aberrations with micronucleus and sister-chromatid exchange frequencies. AB - The mutagenic effects of vinyl chloride monomer in man were studied in the lymphocyte culture with 3 methods: the chromosome aberration assay, the micronucleus assay and the sister-chromatid exchange method. Compared with control, values obtained by these tests are increased in workers occupationally exposed to vinyl chloride. In relation to non-smokers, smokers exposed to vinyl chloride show significant increases in sister-chromatid exchange frequencies. The problem of correlating the results of the chromosome aberration assay with micronucleus and sister-chromatid exchange frequencies is discussed. PMID- 2255321 TI - Chromosome and SCE analysis in peripheral lymphocytes of persons occupationally exposed to cytostatic drugs handled with and without use of safety covers. AB - The frequency of structural chromosome aberrations and sister-chromatid exchanges in peripheral blood lymphocytes of nurses handling cytostatic drugs without a safety cover is compared with that of individuals doing this work exclusively under a safety cover and with that of nurses working under similar conditions but not handling cytostatics. The mean yield of dicentric chromosomes, (4.3 +/- 0.7)/1000 cells, and acentric fragments, (15.4 +/- 1.4)/1000 cells, in the occupationally exposed group is significantly increased in comparison to individuals working with protection (dic: (1.1 +/- 0.4)/1000 cells, ace: (11.2 +/ 1.2)/1000 cells) and nurses not handling cytostatics (dic: (2.1 +/- 0.5)/1000 cells, ace: (9.9 +/- 1.1)/1000 cells). The frequency of chromatid breaks and SCE is not significantly different between these groups (p greater than 0.05). PMID- 2255322 TI - Cytogenetic effect of the thiocarbamate herbicides butylate, molinate and vernolate in the mouse bone marrow micronucleus test. AB - Three thiocarbamate herbicides, butylate (S-ethyl-diisobutylthiocarbamate), vernolate (S-propyl dipropylthiocarbamate) and molinate (S-ethyl-N,N hexamethylenethiocarbamate) were assayed for cytogenetic effect in the mouse bone marrow micronucleus test. Butylate was inactive in bone marrow, vernolate caused a marginal increase in the incidence of micronucleated polychromatic erythrocytes only at a high toxic dose level. Molinate, the N,N-hexamethylene derivative was, however, strongly active in the bone marrow, causing a high frequency of micronucleated erythrocytes, even at subtoxic concentrations. PMID- 2255323 TI - A CASE-SAR analysis of polycyclic aromatic hydrocarbon carcinogenicity. AB - A CASE SAR analysis was performed on a selected database of PAHs to investigate the possible use of the CASE method as an aid for preliminary assessment of carcinogenic potential of untested environmental PAHs. A data set, denoted LEARN, consisting of 78 PAHs and their experimental carcinogenicities was used to 'train' the CASE method and derive the CASE fragments. 8 activating fragments and 4 inactivating fragments were identified. These fragments predicted the activities of 94% of the LEARN set correctly. The biological significance of several of these fragments are rationalized in light of the current theories of PAH carcinogenesis. Using these fragments, the potential activities of a database of 106, mostly untested PAHs, denoted TEST, were predicted. These were compared to 'expert judgement' predictions based on mechanistic considerations in order to evaluate the extent of concordance between these two methods and their respective strengths and weaknesses. Initial poor agreement (64%) was attributed to limitations of the LEARN database involving inadequate representation of 2- and 3 ring PAH subclasses. When these subclasses were excluded from the TEST database, the concordance improved to 90%. The CASE fragments were also used to predict the activities of a database of 24 PAHs, denoted VALIDATE (not included in the LEARN set) for which carcinogenicity data were available. The total prediction accuracy of 75% (89% of the actives correctly identified), despite the structural diversity of the VALIDATE set, provided independent evidence of the utility of the present CASE results. A close examination of the CASE incorrect predictions was conducted to delineate inadequancies of these CASE results in order to provide cautionary guidance for future application of the method. Finally, the present results were compared to the results of a previous CASE analysis based on a more limited PAH data set, and were found to be of greater general utility. It is concluded that the CASE fragments derived in the current study should provide a useful tool for assisting and complementing 'expert judgement' in the preliminary screening of PAHs for carcinogenic activity. PMID- 2255324 TI - Chromosomal monitoring of chromium-exposed workers. AB - A cytogenetic analysis was carried out on peripheral blood lymphocytes of workers exposed to chromite in a ferrochromium plant, to evaluate the possible existence of genetic damage. A quantitatively limited increase in aberrant cell frequencies was detected in subjects working in the furnace sector. The data were analyzed by several statistical approaches. PMID- 2255325 TI - Mutagenicity of adsorbates to a copper-phthalocyanine derivative recovered from municipal river water. AB - Blue cotton, bearing a covalently bound copper-phthalocyanine derivative capable of adsorbing polycyclic aromatic hydrocarbons (PAHs) over 3 rings, was applied to recover mutagens from the Katsura River which is a tributary of the Yodo River. The Ames Salmonella/microsome assay with TA98 and TA100 of the blue cotton concentrate recovered from the river water demonstrated indirect mutagenicity toward TA98. The subfractions separated by Sephadex G-25 gel chromatography also showed direct mutagenicity in strains YG1021 and YG1024, the nitroreductase- and O-acetyltransferase-overproducing derivatives of TA98; this activity was greatly increased by the addition of S9 mix, especially in YG1024. However, these subfractions were less mutagenic with TA98NR or TA98/1,8-DNP6, regardless of whether S9 mix was present or not. The behaviors of these mutagenic activities therefore suggested that frameshift mutagens of both directly mutagenic nitroarenes and indirectly mutagenic aminoarenes were present in the blue cotton concentrate from the river water. PMID- 2255326 TI - Use of a cell hybrid test system to demonstrate that benomyl induces aneuploidy and polyploidy. AB - We have monitored the segregation of a single human chromosome in a human-Chinese hamster hybrid cell line, EUBI, following exposure to benomyl. We found a dose dependent increase in frequency of aneuploidy, but a much more marked induction of polyploidy was noted at the highest benomyl concentration. We confirm the usefulness of this assay for determining genetic risk associated with human exposure to environmental chemicals. PMID- 2255327 TI - Mutagenicity of dibenz[a,c]anthracene and its derivatives in Salmonella typhimurium TA100. AB - The mutagenic activities of dibenz[a,c]anthracene (DB[a,c]A), and its 11 derivatives, including 3 diols, 6 phenols and 2 oxepines, were studied in the TA100 strain of Salmonella typhimurium at doses varying from 0 to 20 micrograms/plate in the presence of a rat-liver S9 (9000 x g) preparation. Among the diols of DB[a,c]A tested DB[a,c]A-10,11-diol was the most mutagenic compound. However, it was consistently less mutagenic than the parent hydrocarbon. Oxepine 1 and oxepine-2 which are believed to be the photoisomerized products of DB[a,c]A 1,2 oxide and DB[a,c]A-3,4-oxide, respectively, were also less mutagenic than DB[a,c]A. In contrast to these results, 4-hydroxyDB[a,c]A was almost twice as active as DB[a,c]A, and 2-hydroxy- and 3-hydroxyDB[a,c]A were even more (4-6 fold) mutagenic than DB[a,c]A. The remaining phenols were relatively inactive or weakly active in this mutagenicity assay. These results provide initial evidence that the bay-region theory may not be applicable to the mutagenesis of DB[a,c]A, and that the angular ring substituted phenols of DB[a,c]A may be involved in the metabolic activation of this highly mutagenic hydrocarbon. PMID- 2255328 TI - Dimethylnitrosamine-induced micronucleus formation in mouse bone marrow and spleen. AB - The present study was designed to obtain information on the kinetics of micronucleus (MN) formation following dimethylnitrosamine (DMN) treatment in mice. Male mice were injected once intraperitoneally with 50 or 100 mg/kg DMN. Bone marrow and spleen were obtained at various sacrifice time-points and processed for micronucleus analysis. The vehicle control group had 0.6 and 0.9 MN polychromatic erythrocytes (PCEs)/1000 PCEs in bone marrow and spleen, respectively. DMN, at 50 mg/kg, caused 3.8, 7.8, 8.5 and 10.2 MN PCEs/1000 PCEs in bone marrow and 8.0, 9.2, 19.3 and 32.8 MN PCEs/1000 PCEs in spleen at 12, 24, 36 and 48 h sacrifice times, respectively. A similar time-related elevation of micronucleus frequency was noted for 100 mg/kg DMN. At each sacrifice time-point, spleen PCEs had a higher micronucleus frequency than bone-marrow PCEs. In general, DMN decreased the proportion of PCEs to total erythrocytes, suggesting toxicity. Thus, this study demonstrates the clastogenic activity of DMN in both bone-marrow and spleen PCEs of mice and shows a time-related pattern in elevating DMN-induced MN PCE frequency. PMID- 2255329 TI - Serotonin uptake blockers influence serotonin autoreceptors by increasing the biophase concentration of serotonin and not through a "molecular link". AB - The mechanism of the attenuation, by serotonin uptake blockers, of the release inhibiting effect of exogenous serotonin autoreceptor agonists was studied in rabbit brain cortex and rat hypothalamus slices. The slices were preincubated with 3H-serotonin and then superfused and stimulated electrically. In rabbit brain slices stimulated by trains of 4 pulses at 100 Hz, 5-carboxamidotryptamine and 5-methoxytryptamine reduced the evoked overflow of tritium, and their concentration-response curves were not changed by any of three serotonin uptake inhibitors, namely citalopram, fluvoxamine and 6-nitroquipazine. In contrast, when the slices were stimulated by trains of 10 pulses at 0.033 Hz, fluvoxamine shifted the concentration-response curve of 5-methoxytryptamine to the right. Experiments with the autoreceptor antagonist metitepine indicated that little, if any, endogenous autoinhibitory tone developed in the course of trains of 4 pulses/100 Hz, irrespective of the absence or presence of uptake inhibitors, as well as during trains of 10 pulses/0.033 Hz in the absence of uptake inhibitors, whereas marked autoinhibition developed when 10 pulses/0.033 Hz were applied in the presence of fluvoxamine. In rat hypothalamic slices stimulated by trains of 4 pulses at 100 Hz, citalopram also failed to change the concentration-response curve of 5-methoxytryptamine. These results indicate that serotonin uptake blockers attenuate the effect of exogenous autoreceptor agonists by an increase in the biophase concentration of released serotonin and, hence, in endogenous autoinhibitory tone, and not by some direct "molecular link" unrelated to the biophase concentration of released serotonin. PMID- 2255330 TI - Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT 1D subtype. AB - The human saphenous vein preincubated with [3H]noradrenaline was used to determine the pharmacological properties of the release-inhibiting presynaptic serotonin (5-HT) receptor on the sympathetic nerves. The overflow of tritium evoked by transmural electrical stimulation (2 Hz) was concentration-dependently inhibited by drugs known to stimulate 5-HT receptors in the following rank order: oxymetazoline greater than or equal to 5-HT greater than 5-carboxamidotryptamine = 5-methoxytryptamine = sumatriptan greater than tryptamine greater than N,N(CH3)2-5-HT = yohimbine = 8-hydroxy-2-(di-n-propylamino)-tetraline. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B and 5-HT1D binding sites, but not with those for 5-HT1A or 5-HT1C binding sites. 5-Aminotryptamine, methysergide, ipsapirone, cyanopindolol, SDZ 21009 and metergoline dit not produce a significant inhibition. Metitepine and methysergide antagonized the inhibitory effect of 5 HT, whereas spiroxatrine, propranolol, ketanserin and ICS 205-930 did not. These data exclude the idea that the inhibitory presynaptic 5-HT receptor on the sympathetic nerves belongs to the 5-HT2 and 5-HT3 receptor class; the pattern of agonist potencies suggests that the receptor is very similar to the 5-HT1D receptor subtype. PMID- 2255331 TI - Effects of the 5-HT1 receptor agonists DP-5-CT, CGS 12066B, and RU 24969 on plasma adrenaline and glucose levels in the rat. AB - Recent results have indicated that the 5-HT1A receptor subtype mediates the adrenaline-releasing and hyperglycemic effects of 8-hydroxy-2-(di-n propylamino)tetralin in the rat. The aim of this study was to analyse, by means of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5 carboxamidotryptamine (DP-5-CT), whether these 5-HT1A receptors are peripherally or centrally localised. In view of the appreciable affinity of DP-5-CT for the 5 HT1D receptor subtype, the effects of the mixed 5-HT1B/5-HT1D receptor agonist 7 trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (CGS 12066B), and the mixed 5-HT1A/5-HT1B/5-HT1D receptor agonist 5-methoxy-3(1,2,3,6 tetrahydropyridine-4-yl)1H-indole (RU 24969) were also investigated. Administration of DP-5-CT (0.3 and 1 mg/kg i.v.) increased plasma glucose levels dose-dependently, whereas only the 1 mg/kg dose of DP-5-CT elicited a rise in plasma adrenaline levels. In contrast, CGS 12066B (1.5 and 4.5 mg/kg i.v.) did not affect either plasma adrenaline or plasma glucose levels. Administration of RU 24969 (0.5-4.5 mg/kg i.v.) increased dose-dependently both plasma adrenaline and glucose levels. The data suggest that central 5-HT1A receptors, but neither 5 HT1B nor 5-HT1D receptors, regulate plasma adrenaline and glucose levels. PMID- 2255332 TI - Epithelium-derived inhibition of [3H]acetylcholine release from the isolated guinea-pig trachea. AB - To investigate presynaptic, regulatory mechanisms on parasympathetic nerve fibres innervating the airways, the release of newly-synthesized [3H]acetylcholine from the isolated trachea was studied. Reverse phase HPLC followed by liquid scintillation spectrometry was used to separate and quantify the radioactive compounds choline, phosphorylcholine and acetylcholine in the incubation medium and the tissue. During the incubation of the tracheae with [3H]choline a significant synthesis of [3H]acetylcholine (35,000 dpm/preparation) and [3H]phosphorylcholine (500,000 dpm/preparation) occurred. In epithelium-deficient tracheae the formation of [3H]phosphorylcholine was enhanced, whereas the content of [3H]acetylcholine remained unchanged. The spontaneous outflow of tritium consisted mainly of [3H]phosphorylcholine (900 dpm/3 min) and [3H]choline (800 dpm/3 min); [3H]acetylcholine was only a minor fraction (50 dpm/3 min). Electrical stimulation of tracheae with intact epithelium caused only a small release of [3H]acetylcholine (460 dpm in the sample obtained during stimulation), but a considerable outflow of [3H]phosphorylcholine (1,900 dpm) without affecting the outflow of [3H]choline. Electrical stimulation of epithelium-deficient tracheae, however, induced a substantial release of [3H]acetylcholine (2,400 dpm), but only a small outflow of [3H]phosphorylcholine. Chemical stimulation (30 mumol/l veratridine) also caused a large release of [3H]acetylcholine (1,700 dpm) without affecting the outflow of [3H]phosphorylcholine or [3H]choline. Indomethacin (3 mumol/l) enhanced the electrically-evoked release of [3H]acetylcholine from tracheae with intact epithelium by 89%. The present experiments demonstrate a strong inhibition by the epithelium of the electrically evoked release of [3H]acetylcholine from the isolated guinea-pig trachea. Cyclooxygenase products of arachidonic acid do not appear as the main mediators of the epithelium-derived inhibition of acetylcholine release. PMID- 2255333 TI - Interaction of p-F-HHSiD (p-Fluoro-hexahydrosila-difenidol) at muscarinic receptors in guinea-pig trachea. AB - 1. para-Fluoro-hexahydrosila-difenidol (p-F-HHSiD) has been proposed as an M3 selective antagonist. However, the M3 selectivity is variable in that it exhibits a high pA2 value for M3 muscarinic receptors in guinea-pig ileum but a low value at muscarinic receptors in guinea-pig trachea. 2. The pA2 value in the trachea was found to be agonist independent since similar pA2 values were found when acetylcholine, carbachol, (+)-cis-dioxolane or OXA-22 were used (7.13, 7.03, 6.85 and 6.97, respectively). The pA2 value was not meaningfully increased when the equilibrium period was increased from 60 to 180 min. The pA2 value was unaffected by blockade of M1 or M2 receptors, using 0.1 microM pirenzepine or methoctramine (7.03 and 7.14, respectively). p-F-HHSiD and atropine appeared to act at the same site, as adjudged by combination concentration-ratio studies. 3. The pA2 values for p-F-HHSiD vary by 10 fold between ileal (8.0) and tracheal M3 receptors (7.0). The precise reason for this is unknown, but appears to be unrelated to conditions of disequilibrium that could be detected. The antagonist should therefore only be employed to distinguish M3 or M1 from M2 receptors. In this respect, although the M1/M3 vs M2 discrimination is relatively large (68 fold), p F-HHSiD exhibits similar properties to other putative M3 selective antagonists such as 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) or the parent compound, hexahydrosiladifenidol (HHSiD). PMID- 2255334 TI - Chronic nicotine treatment changes differentially the effects of acute nicotine on the three main dopamine metabolites in mouse striatum. AB - The effect of chronic treatment with nicotine on striatal dopamine metabolism was studied in mice by measuring the striatal concentrations of dopamine and its metabolites 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). (-)-Nicotine was administered for 7 days using subcutaneously implanted nicotine releasing reservoirs. The release of nicotine was confirmed by measuring nicotine and cotinine concentrations in the plasma. To study the possible tolerance induced by chronic nicotine treatment, acute challenge doses of (-)-nicotine (either 3 mg/kg given once or 1 mg/kg repeated 4 times at 30 min intervals) were given to mice on the 7th day after the implantation. At an ambient temperature of 20-22 degrees C, acute nicotine treatment induced marked hypothermia (-5.2 to -6.7 degrees C) in both chronic nicotine treated and control mice, an effect that was prevented by elevating the ambient temperature to 32-34 degrees C. Chronic nicotine treatment did not per se alter striatal dopamine metabolism. Acute nicotine administration altered the striatal dopamine metabolism in a temperature-dependent manner. In mice kept at 20-22 degrees C, the DOPAC concentration rose slightly but concentrations of 3-MT and HVA fell, indicating a decrease in the release of dopamine. In contrast, in mice kept at 32-34 degrees C the DOPAC and HVA concentrations were clearly elevated by acute nicotine, whereas the concentration of 3-MT was not altered. In these normothermic mice chronic nicotine pretreatment did not alter the effects induced by acutely administered nicotine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255335 TI - Inhibition by the putative potassium channel opener pinacidil of the electrically evoked release of endogenous dopamine and noradrenaline in the rat vas deferens. AB - The effect of pinacidil on the release of endogenous noradrenaline and dopamine from the sympathetic innervation of the rat vas deferens was examined. Amine release was evoked by electrical stimulation (1, 2, 5 and 10 Hz) or by depolarization with high potassium (75 mmol/l) in the medium. Dopamine and noradrenaline were measured by means of high pressure liquid chromatography with electrochemical detection. Pinacidil (1, 5, 10 and 50 mumol/l) produced a concentration-dependent inhibition of the electrically stimulated (2 Hz) overflow of noradrenaline and dopamine. Only pinacidil 50 mumol/l increased the spontaneous loss of dopamine and noradrenaline. The inhibitory effects of pinacidil (5 mumol/l) on amine overflow were also observed at other frequencies of stimulation (1, 5 and 10 Hz). The magnitude of the inhibitory effect on noradrenaline release was approximately the same at all frequencies (63% to 56% reduction); for dopamine, the higher the frequency of stimulation, the greater the inhibitory effect of pinacidil (up to 73% reduction). When the preparations were continuously stimulated for 70 min at 2 Hz, pinacidil (5 mumol/l) reduced the overflow of dopamine and noradrenaline during the first 40 or 30 min of stimulation only. The addition of phentolamine (1 mumol/l) to the perifusion medium slightly reduced the inhibitory effect of pinacidil on amine overflow, but the inhibition by pinacidil remained statistically significant. Tetraethylammonium (10 mmol/l) completely abolished the inhibitory effect of pinacidil (10 mumol/l). Pinacidil (5 mumol/l) did not reduce the potassium-evoked release of the amines. The results demonstrate that pinacidil impairs transmitter release from the sympathetic innervation of the rat vas deferens, probably as a consequence of the opening of potassium channels. PMID- 2255336 TI - Regional differences in the electrically stimulated release of endogenous and radioactive adenosine and purine derivatives from rat brain slices. AB - The release of both radioactive and endogenous purines was investigated in rat brain cortical, hippocampal and striatal slices at rest and following stimulation with electrical fields. Purines were labelled by incubating the slices with 3H adenine. The purine efflux at rest and that evoked by electrical stimulation (10 Hz. 5 min) was analyzed by HPLC with ultraviolet absorbance detection. Both radioactive and endogenous purines in the effluent consisted mainly of hypoxanthine, xanthine, inosine and adenosine. No qualitative differences in the composition of the released purines were found in the three areas investigated. Electrical stimulation evoked a net increase in both radioactive and endogenous purine release. However the increase in 3H-adenosine following electrical stimulation was twice as large as that of endogenous adenosine. The electrically evoked release of both radioactive and endogenous purines was greatest in hippocampal slices and progressively smaller in cortical and striatal slices. In the three areas the addition of 0.5 microM tetrodotoxin to the superfusing Krebs solution brought about a similar (83-100%) reduction in evoked 3H-purine and endogenous purine release. Superfusion of the slices with calcium-free Krebs solution containing 0.5 mM EGTA reduced evoked release of 3H-purines by 58-60% and that of endogenous purine components by 54-89%. The results demonstrate similar characteristics for both radioactive and endogenous purine release but indicate that the most recently synthetized adenosine is the most readily available for release. The features of the electrically evoked purine release support a neuronal origin of adenosine and derivatives and are consistent with the hypothesis of discrete regional differences in adenosine neuromodulation. PMID- 2255338 TI - Desipramine inhibits sympathetic nerve activity in the rabbit. AB - The aim of the study was to determine the sites of action of intravenously administered desipramine on the sympathetic nervous system in anaesthetized rabbits (alfadolone + alfaxalone). Renal postganglionic sympathetic nerve activity was measured in order to determine central nervous and ganglionic effects. The clearance of noradrenaline from the plasma was determined with an isotope tracer method. From the noradrenaline clearance and the plasma concentration of noradrenaline the noradrenaline spillover rate was calculated. These parameters as well as blood pressure and heart rate were measured before (basal values) and at the end of 20-min infusions of sodium nitroprusside, which was given in order to modulate efferent sympathetic nerve activity through the baroreceptors. Desipramine 0.5 mg kg-1 + 0.05 mg kg-1 h-1 (bolus injection followed by infusion) and 2 mg kg-1 + 0.2 mg kg-1 h-1 dose-dependently inhibited basal sympathetic nerve activity and the noradrenaline clearance. Desipramine had no effect on basal blood pressure, noradrenaline spillover rate or heart rate. Nitroprusside produced hypotension and simultaneously increased sympathetic nerve activity, noradrenaline spillover rate and heart rate; the clearance of noradrenaline was reduced with decreasing blood pressure. The relationship between sympathetic nerve activity and blood pressure was shifted by desipramine in a manner indicating central sympathoinhibition. Desipramine had no effect on the relationship of the noradrenaline spillover rate to blood pressure, whereas it shifted the heart rate-blood pressure relationship in a manner indicating an enhancement of reflex cardioacceleration. In a separate series of experiments, desipramine also inhibited sympathetic nerve activity in baroreceptor-denervated animals. The results show that desipramine centrally inhibits sympathetic outflow in the rabbit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255340 TI - Injury in North Carolina. PMID- 2255339 TI - Cancer of the female breast. Improving the public's health through early detection. AB - Decision makers who represent the public need to understand the extent of the breast cancer problem, the potential for improvement, and the actions needed to achieve this potential. Informed, dedicated physicians, individually and collectively, are instrumental and can be most effective leaders in this process. There are several evidences of the fine tradition of the medical profession to advocate practices and policies in the interest of the best health of our patients. The North Carolina Medical Society recently adopted a position statement encouraging the provision of screening mammograms and pap smears by both private and self-insured third party payors; the North Carolina Academy of Family Practice recently adopted a position statement urging priority be placed on allocating resources for efficacious preventive services; the multiple specialty organizations developed the widely recognized national guidelines for early breast cancer detection; and the ACR continues its efforts to assure quality mammography services. To the end that this paper has informed and stimulated further sharing, discussion or debate about the extent of the breast cancer problem, the potential for improvement, and the actions needed to achieve this potential, it has accomplished its purpose. To the end that the physician community acts to improve early breast cancer detection, we will have fulfilled the common purpose that binds us as physicians to one another and to the people we are privileged and bound to serve. PMID- 2255337 TI - An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta. AB - The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 mumol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 +/- 3.5% or 63 +/- 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn2+, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in "Ca2(+)-free" medium. Ryanodine -in the presence of extracellular Ca2(+)-caused a slight increase in resting tension, but did not modify the NA-induced contraction. In "Ca2(+)-free" medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to "Ca2(+)-free" medium. The phasic component was identified as elicited by Ca2+ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca2+ depleted tissues (80 min in "Ca2(+)-free" solution) were exposed to Ca2+ in the presence of Mn2+ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn2+ and cromakalim blocked the refilling of the store. It can be concluded that activation of alpha 1-adrenoceptors in the rat aorta by NA elicits Ca2(+)-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn2+. The Ca2+ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn2(+) sensitive pathway. PMID- 2255341 TI - Public health and the AIDS epidemic in North Carolina. PMID- 2255342 TI - Immunizing our patients in the '90s. PMID- 2255343 TI - Arthritis. Treatment & management. PMID- 2255344 TI - Smoking-attributable mortality, morbidity and economic costs in North Carolina. PMID- 2255345 TI - Enactment of mandatory seatbelt-use legislation. An analysis of the political process in North Carolina. PMID- 2255346 TI - [Osteogenesis imperfecta; more than just many fractures]. PMID- 2255347 TI - [Osteogenesis imperfecta]. PMID- 2255348 TI - [Is breech presentation an indication for cesarean section?]. PMID- 2255349 TI - [Use and abuse of androgens; side effects and risks]. PMID- 2255350 TI - [Esophagus resection and reconstruction without thoracotomy; initial results]. AB - From November 1, 1986 to December 1, 1989, 100 patients with squamous cell carcinoma (n = 35), adenocarcinoma (n = 61) or 'other' carcinoma (n = 4) of the oesophagus or the gastroesophageal junction were resected and reconstructed. There were 71 men and 29 women with a mean age of 63 years (35-77 yrs). In 80 patients the tumour was localised in the distal oesophagus or the gastroesophageal junction. In 20 patients the tumour was localised more proximally. In all patients the oesophageal resection was performed transhiatally without thoracotomy with blunt dissection. Reconstruction was performed with a stomach tube (n = 84) or colonic interposition (n = 16). Postoperative pulmonary complications were seen in 25% of the patients. Leakage of the cervical anastomosis was seen in 6 patients. In-hospital mortality was 4%. Oesophageal resection without thoracotomy appears to be an operation with reduced morbidity leading to a marked decrease in postoperative mortality. PMID- 2255351 TI - [Efficacy of mass screening for breast cancer; reduced mortality nationally and internationally]. AB - Breast cancer screening trials in several countries have proved to reduce breast cancer mortality. However, the trials show considerable differences in the extent of this reduction. The Swedish projects in Kopparberg/Ostergotland and Malmo are the most similar to the Dutch situation. The confidence intervals of the effect estimates of both projects are large. A critical review of all differences cannot yet lead to a conclusion on the difference in the estimated effects of both trials. Assuming equal mammographic quality in both projects, a reduction of 33% in breast cancer mortality for women in the age-group of 50 to 70 years seems a good estimate for similar projects. This assumption applied to a Dutch nationwide project, it will eventually lead to a reduction in breast cancer mortality of 16% for the entire population. In the year 2015 about 700 women will not die of breast cancer who would have without screening. PMID- 2255352 TI - [The benefit of external version in full-term breech presentation]. AB - We report a randomised controlled trial of external version in 52 women with breech presentation after 36 weeks' gestation; 83% gave informed consent to undergo the management to which they had been randomized. Only 5% of initial attempts without tocolysis succeeded, but 31% of the failures subsequently had a successful version under tocolysis. External version resulted in a small decrease in the frequency of breech presentation at birth (64% vs. 74%), and in an unexpected increase in the caesarean section rate (28% vs. 11%). The increase in caesarean section rate could be attributed to failed versions, which apparently greatly influenced the choice between abdominal and vaginal delivery. Our findings and data from similar research suggest that benefits of external version at term may not apply to populations with a low caesarean rate, unless versions are carried out with maximal efficiency (which, on the basis of available data, would imply tocolysis) or so indifferently that failed attempts do not influence the choice between abdominal and vaginal delivery. PMID- 2255353 TI - [Criteria for differential diagnosis in cardial symptoms; left- or right-sided chest pain?]. AB - We studied the localization of pain in the acute phase of myocardial infarction in comparison with localization in non-cardiac chest pain. Myocardial infarction patients could not be differentiated from patients with non-cardiac chest pain in localization of pain on mid-chest, left side of the chest and left arm. However, myocardial infarction patients reported pain on the right side of the chest and in the right arm twice as often as non-cardiac chest pain patients. Results are similar when patients indicated the localization of the pain symptoms on attending the Emergency Coronary Care Unit, or when asked five days later. Pain symptoms on the right side of the chest and the right arm differentiate better between myocardial infarction and non-cardiac chest pain than the 'classical' symptom pattern. PMID- 2255355 TI - [Carpal tunnel syndrome]. PMID- 2255354 TI - [Cerebral disseminated lupus erythematosus; brain-racking for patient and physician]. AB - A 30-year-old woman, who in the past was diagnosed as having systemic lupus erythematosus (SLE) and had been treated accordingly, consulted us with neuropsychiatric symptoms, including mutism and catatonia. ANA and anti-dsDNA in serum were negative, and she did not fulfill the ARA criteria for a diagnosis of SLE. However, in view of her history and the fact that she developed convulsions and a transient, unexplained period of leukopenia during admission, her current illness could be interpreted as a cerebral manifestation of SLE. After increasing the dosage of prednisone, she recovered almost completely from this episode. The literature concerning possible procedures to diagnose neuropsychiatric manifestations of SLE is reviewed; it turns out that especially the primary form of cerebral SLE often causes diagnostic problems. PMID- 2255356 TI - [Administration of vitamin K to newborn infants and infants]. PMID- 2255357 TI - ['You could be that one'; risk experience and choice behavior in medical technology]. PMID- 2255358 TI - [Does the incidence of heart infarct decrease together with the mortality?]. PMID- 2255359 TI - [Galactorrhea]. PMID- 2255360 TI - [Chronic benign pain in children]. PMID- 2255361 TI - [Wrist disorders in juvenile chronic arthritis]. AB - In Juvenile Chronic Arthritis the wrist often is involved. Synovitis of this joint gives rise to several types of disintegration, which can lead to serious deformities and loss of function. Therapeutical considerations should be based upon knowledge of these types of disintegration and the natural history. PMID- 2255362 TI - [Early cholecystectomy for acute cholecystitis; effect of length of symptoms on morbidity and mortality]. AB - In this retrospective study the results of "early' cholecystectomy for acute cholecystitis were analysed, especially the influence of duration of symptoms on morbidity and mortality. During a 4-year period 122 patients underwent early cholecystectomy for acute cholecystitis. The mean age was 64 years (range 20 101). Cholecystectomy was performed in 93 patients, 25 underwent cholecystectomy and common bile duct exploration and the remaining 4 patients cholecystostomy. The mortality was 1.6% (2 patients 88 and 89 years of age). Biliary surgery related complications and wound infection occurred in 14 and 11 patients respectively. There was no significant difference in morbidity and mortality according to duration of symptoms (2 days versus 2-7 days). The duration of symptoms is not a major contraindication to early cholecystectomy. Early cholecystectomy appears to be a safe procedure for acute cholecystitis for patients within 7 days after onset of symptoms. PMID- 2255363 TI - [Altered sensitivity of Escherichia coli for antibiotics in the population]. AB - Faecal carriage rates for antibiotic-resistant Escherichia coli were determined in a Dutch urban population during two periods with an interval of seven years. In the period 1978-1980 faecal samples were collected from 624 persons and in 1987 from 154 persons. E. coli was isolated from samples of 577 persons in the first period and from samples of 125 persons in the second period. The frequency of E. coli-carrying persons found with tetracycline-resistant E. coli decreased from 42% in 1978-1980 to 20% in 1987 (p less than 0.001). The frequency of persons with a predominantly tetracycline-resistant E. coli flora (greater than 50% of the E. coli flora resistant) decreased in the period 1978-1980 from 12% to 6% in 1987 (p less than 0.05). There was an increase in frequency of persons found with a predominantly ampicillin-resistant E. coli flora from 5% in 1978 1980 to 11% in 1987 (p less than 0.01). Antimicrobial resistance in the open population is a dynamic process. Data concerning an association with antibiotic consumption are mostly lacking. Further intervention studies on the influence of antibiotic policies are needed. PMID- 2255364 TI - [Arthroscopic suturing of the meniscus]. AB - A retrospective study (n = 12) was made of the results of arthroscopical suturing of menisci. Suturing is indicated in peripheral longitudinal meniscal tears in young, active people. Recurrent locking symptoms were found in one patient and quadriceps atrophy in another. The mean follow-up period was 8.2 (6-12) months. There were no complications. Our findings show that the method is feasible; the results were comparable with those reported in the literature and are encouraging for meniscus-sparing therapy. PMID- 2255365 TI - [Echography in focal non-steatosis of the liver; diagnostic problems]. AB - After a brief review of different patterns of steatosis of the liver three patients with focal non-steatosis are presented in whom the sonographic aspects were confused with neoplastic liver processes. CT established the diagnosis of focal non-steatosis in all three patients and liver biopsy in one. If in a steatotic liver one or more focal relatively echo-poor lesions are detected on ultrasonography, CT and (or) biopsy should be considered for definitive diagnosis. PMID- 2255366 TI - [A family with hereditary spherocytosis, discovered following an infection with human parvovirus B19]. PMID- 2255367 TI - [First Heart Aid: what happens to patients who are not immediately admitted?]. PMID- 2255368 TI - [Symptoms and injuries of the locomotor systems in dancers]. PMID- 2255369 TI - [Contact allergy for Alstroemeria (inca lily)]. PMID- 2255370 TI - [Rheumatic manifestations of leprosy]. PMID- 2255371 TI - [Improved efficacy of adjuvant chemotherapy by combination with immunostimulants]. PMID- 2255373 TI - [The classification of non-Hodgkin lymphoma; considerations with the working formulation]. PMID- 2255372 TI - [The effect of coffee on serum cholesterol level]. PMID- 2255374 TI - [Dupuytren's disease]. PMID- 2255375 TI - [Farmacotherapeutisch Kompas 1990-1991]. PMID- 2255376 TI - [The structured summary: a tool for reader and author]. AB - OBJECTIVE: To determine and to compare the information contained in structured abstracts in original articles in Annals of Internal Medicine (AIM), British Medical Journal (BMJ), New England Journal of Medicine (NEJM) and of abstracts that have been published in Nederlands Tijdschrift voor Geneeskunde (NTvG). SETTING: Editorial office NTvG. DESIGN: Descriptive. MATERIAL AND METHOD: Critical reading of 15 original articles of AIM (5), BMJ (5) and NEJM (5) in 5 consecutive issues starting from 1 March 1990 and all original articles of 6 consecutive issues of NTvG starting from 7 april 1990. According to the criteria of the 'ad hoc working group for critical appraisal of the medical literature' the amount of information in all foreign abstracts and 10 selected abstracts of NTvG were determined. The authors made structured abstracts of all read articles of NTvG. RESULTS: Structured abstracts of AIM, BMJ and NEJM are clear and detailed. However information about key sociodemographic features of patients, their selection and the way of statistical analysis of the results was often missing. In NTvG articles essential information was lacking with respect to objective, design, setting of the study, sociodemographic features of patients, and patients and methods. Structured abstracts of articles in NTvG take more space: an average of 266 instead of 164 words. CONCLUSION: Structured abstracts take more space but are more informative. Authors of original articles in NTvG are advised to prepare structured abstracts. Editors and peer reviewers should ascertain that no essential information is lacking. PMID- 2255377 TI - [The effect of elevated ozone levels in the ambient air on lung function of children engaged in sports]. AB - In the summer of 1989, ozone levels in the ambient air were regularly found to be increased in The Netherlands. The question was studied whether this affected pulmonary function of children aged 7 to 12 years practising sports in the open air. Before and after sessions of training in the open air, the peak expiratory flow rate was determined using peak flow meters (mini-Wright). This was done on 37 different days with varying ozone concentrations. Measurements were carried out on four or more days in a total of 65 children. No correlation between ozone concentration during training and differences between pre- and post-training peak flows was found. No correlation was found either between the maximal ozone concentration on a given day and the peak flow at the end of training on that day. However, a negative correlation was found between the maximal ozone concentration on the day preceding the pulmonary function tests and the peak flow after the training. PMID- 2255378 TI - [Closure of the persistent ductus arteriosus (Botalli) using a catheter procedure; the initial 50 patients treated in The Netherlands]. AB - Experience gained with non-surgical catheter occlusion of patent ductus arteriosus in 50 patients (1-65 years) is described. Embolisation of the Rashkind device into the right pulmonary artery occurred in 1 patient. In another patient the device was removed because the prongs of the proximal umbrella could not be visualized. In 4 patients a considerable residual shunt was successfully treated with implantation of a second device. In 1 of these 4 patients this resulted in disappearance of considerable haemolysis as well. Five patients, however, still have a--haemodynamically insignificant--residual shunt. In 43 patients catheter occlusion of the ductus arteriosus was 100% successful. The advantages and disadvantages of this method are briefly compared with those of surgical treatment. PMID- 2255379 TI - [Trombiculiasis, and epidemic of prurigo caused by mites]. AB - In four villagers parasitic prurigo caused by the autumnal chigger (Neotrombicula autumnalis) was diagnosed. The clinical picture consisted of intensely itchy, erythematous papules, at sites where clothes fitted tightly or in body folds. Further investigation in the village revealed that in 16 of the 48 homes at least one person in the preceding two months had suffered from prurigo possibly caused by the autumnal chigger. The characteristics of the parasite, the clinical picture, treatment and prevention are discussed. PMID- 2255380 TI - [Adjuvant treatment of colon and rectum carcinoma: one step ahead]. PMID- 2255381 TI - [Premenstrual syndromes]. PMID- 2255382 TI - [The 'freckle bus'; an unhealthy phenomenon or a sober-minded experiment?]. PMID- 2255383 TI - Metabolic fate of injected radiolabelled dopamine and 2-fluorodopamine in rats. AB - In evaluating positron-emitting analogs of dopamine (DA) as possible imaging agents for visualizing tissue sympathetic innervation and function, the metabolic fate of systemically injected [3H]-DA or [14C]-DA was compared with that of [3H] 2-fluoroDA in plasma and in sympathetically innervated tissues (left ventricle, spleen and salivary glands) of rats. By 60 min after the injection of [3H]-DA or [3H]-2-fluoroDA, concentrations of [3H]-DA. [3H]-2-fluoroDA, [3H]-norepinephrine ([3H]-NE) and [3H]-2-fluoroNE in tissue exceeded concentrations in plasma by up to several thousand-fold. Whereas most of the radioactivity in tissue was in catechols, radioactivity in plasma was due to O-methylated metabolites of DA, including homovanillic acid (HVA) and of NE, including normetanephrine (NMN) and methoxyhydroxphenylglycol (MHPG). Estimated ratios of tissue: blood radioactivity at 60 min after injection of [3H]-2-fluoroDA were 4.10 for the heart, 1.91 for the spleen and 2.10 for the salivary glands. The patterns of levels of catechol metabolites and analogs of HVA in plasma and effects of blockade of neuronal uptake with desipramine suggested that [3H]-2-fluoroDA was not as efficiently removed by neuronal uptake and not as efficiently beta-hydroxylated as the non fluorinated compound. Concurrent administration of [3H]-DA and large amounts of non-radioactive 2-fluoroDA did not substantially alter the pattern of metabolites of [3H]-DA in plasma. After injection of [18F]-fluoroDA, visualization of sympathetic innervation of tissue should be feasible by position emission tomography. PMID- 2255384 TI - N-ethylmaleimide irreversibly inhibits the binding of [3H]threo-(+-) methylphenidate to the stimulant recognition site. AB - N-Ethylmaleimide, a nonspecific protein modifier which reacts selectively with the sulfhydryl group of cysteinyl residues under controlled conditions, irreversibly inhibited the binding of [3H]threo-(+/-)-methylphenidate to a subset of stimulant binding sites in striatal tissue membranes from the rat in vitro. The inhibition was marked by a decrease in the Bmax of binding of the radiolabelled stimulant drug, while the KD remained unchanged. Pretreatment with excess unlabelled methylphenidate afforded complete protection from inactivation of the binding site by N-ethylmaleimide. Uptake of [3H]dopamine into striatal synaptosomes was likewise reduced after treatment with N-ethylmaleimide; pretreatment with large concentrations of methylphenidate provided partial protection from inactivation of transport. These findings suggest that the stimulant recognition site on the dopamine transport complex contains one or more cysteinyl residues. PMID- 2255385 TI - The effects of MK801 on the high pressure neurological syndrome in the baboon (Papio anubis). AB - The in vivo neurophysiological interactions of the non-competitive NMDA receptor antagonist MK801 with the High Pressure Neurological Syndrome have been investigated in the primate Papio anubis. A hyperbaric chamber was used to achieve environmental pressures of 61 ATA (atmospheres absolute) over a period of 5 hr. Eight animals underwent 2 compressions each, one following pretreatment with 0.03 mg/kg (i.v.) MK801, the other a control. Half of the animals received MK801 on their first exposure. Mild signs of the high pressure neurological syndrome, e.g. paw and limb tremor were first observed between 10 and 20 ATA and more severe signs, e.g. whole body tremor, myoclonus and vomiting, appeared after 50 ATA. The onset pressures for the various signs were increased by 10-17 ATA when the animals received MK801 (P = 0.06) and the severity of the signs, over the whole range of pressures at which they appeared, was significantly reduced (P less than 0.001). Additional experiments showed that MK801 afforded considerable protection, at pressures up to 81 ATA, but doses larger than those used for the main experiment produced signs of tranquilisation and sedation. Changes in the EEG were observed in channels associated with the frontal, parietal and occipital regions. Amplitude and frequency spectra were calculated and trends with pressure in the 4 conventional wavebands were analysed. The most striking change was a decrease in amplitude of delta waves (P less than 0.001), which was ameliorated by MK801 (P less than 0.001). PMID- 2255386 TI - Influence of calcium channel inhibitors upon the anticonvulsant efficacy of common antiepileptics against pentylenetetrazol-induced convulsions in mice. AB - Among three calcium channel inhibitors studied, nifedipine (20 mg/kg) moderately inhibited pentylenetetrazol (115 mg/kg, s.c.)-induced convulsions, whilst diltiazem (up to 20 mg/kg) and verapamil (up to 20 mg/kg) were without effect. The combinations of nifedipine (10 and 20 mg/kg) with valproate (100 mg/kg) or phenobarbital (6.25 mg/kg) resulted in significant protection against pentylenetetrazol-induced seizures. Combined treatment of nifedipine (5-20 mg/kg) with ethosuximide (100 mg/kg) also provided a clearcut anticonvulsant action. The antiepileptic drugs alone, in the above doses, were ineffective. The combination of diltiazem (10-20 mg/kg) and ethosuximide (100 mg/kg) produced protection against pentylenetetrazol, comparable to that of ethosuximide (200 mg/kg) alone. No pharmacokinetic interactions were found in the case of ethosuximide, whilst nifedipine (10 mg/kg) increased the levels of phenobarbital and valproate in plasma. The combination of diltiazem with the remaining antiepileptics were ineffective. Verapamil (up to 20 mg/kg) was without effect upon the action of the antiepileptic drugs tested. Finally, none of the calcium channel inhibitors studied influenced the action of diazepam (0.2 mg/kg). It may be concluded that combinations of ethosuximide, with either nifedipine or diltiazem, may be promising for the treatment of absence epilepsy. PMID- 2255387 TI - Intranigral microinjection of neurotensin suppresses feeding in food deprived rats. AB - This study was conducted to determine whether the substantia nigra is involved in the anorectic effect of centrally administered neurotensin. Microinjection of neurotensin (2.5 - 10.0 micrograms) into the substantia nigra produced a significant suppression of feeding in 18 hour food deprived rats. To determine if the anorectic effect resulted from a general impairment of sensory-motor functioning, eight behaviors were measured in a separate study. Significant effects were found in only two of the eight behavioral categories (sniffing and eating), and only at the highest neurotensin dose (10.0 micrograms). These results suggest that the substantia nigra may be involved in the anorectic effect of neurotensin. PMID- 2255388 TI - Sector-dependent neurotoxicity of ethylcholine aziridinium (AF64A) in the rat hippocampus. AB - The present study was aimed at measuring the distribution of ethylcholine aziridinium (AF64A)-induced cholinotoxicity within the hippocampus 6 days after bilateral (icv) administration of 1, 2 or 3 nmol, or vehicle. The dissected hippocampus was sectioned with a vibratome into 5 parallel sectors distributed along its long axis from its thalamic surface (medial) to its cortical surface (lateral). In vehicle-treated rats, the high affinity cholinergic transport (HAChT), choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were distributed according to a gradient of increasing activity, extending from the lateral to the medial surface of the hippocampus. After treatment with AF64A, the normal gradient of enzyme activity was profoundly disrupted at all doses of AF64A and the core sectors of the hippocampus were significantly more affected than the superficial sectors. The HAChT gradient was progressively abolished with increasing doses of toxin, and the effect was maximal at 2 nmol. PMID- 2255389 TI - Effects of monoamine reuptake blockade on ponto-geniculo-occipital wave activity. AB - Norepinephrine (NE) and serotonin (5HT) likely inhibit the generation of ponto geniculo-occipital (PGO) waves. Either desipramine (DMI) or sertraline (SER:1S,4S N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl amine) was administered in the cat for 2.5 weeks to probe noradrenergic and serotonergic mechanisms, respectively. Placebo days were compared with the first day of drug and with days that followed 2.5 weeks of drug (chronic). PGO rates during REM sleep and the preceding transition period were significantly decreased by either chronic DMI or SER. Cat PGO waves resemble waves that accompany alerting to intense or novel stimuli in wakefulness. Depressive disorders in humans have features of hyperarousal; PGO wave suppression by antidepressant drugs may relate to clinical antidepressant actions. PMID- 2255391 TI - Ischemia-induced slowly progressive neuronal damage in the rat brain. AB - Ischemic neuronal damage has been believed to make rapid progress in the course of a few days even in delayed selective neuronal death, to say nothing of acute brain necrosis. In the present study, however, we demonstrate for the first time a new type of ischemia-induced neuronal damage which progresses in the course of several weeks or a few months and we tentatively call this process "slowly progressive neuronal damage". We have focused on the chronological changes of neuronal damage in the dorsolateral striatum and neocortex following various durations of transient middle cerebral artery occlusion, which does not cause cerebral infarction and is clinically designated "transient ischemic attack". In the rats subjected to 15 min middle cerebral artery occlusion, the neocortex and lateral striatum were rarely damaged, whereas the small to medium-sized neurons only in the narrow area restricted to the dorsal striatum showed slowly progressive neuronal damage. Prolongation of ischemic duration to 30 min accelerated the evolution of neuronal damage in the dorsolateral striatum and also extended the distribution of neuronal damage to the neocortex, especially to layer III and more superficial layers. Further prolongation of ischemic duration to 45 min resulted in more rapid progress of selective neuronal death in those areas described above, whereas no animal escaped 60 min ischemia, without acute total tissue necrosis in the middle cerebral artery territory. Ischemia-induced slowly progressive neuronal damage may be implicated in the pathogenesis of such slowly progressive neurologic deterioration as dementia or Parkinsonism in patients with cerebral arteriosclerosis. PMID- 2255390 TI - MK-801 pretreatment enhances N-methyl-D-aspartate-mediated brain injury and increases brain N-methyl-D-aspartate recognition site binding in rats. AB - Direct intracerebral administration of N-methyl-D-aspartate typically produces focal brain injury. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10 immi ne maleate (MK-801), a non-competitive N-methyl-D-aspartate antagonist, can protect against N-methyl-D-aspartate-mediated brain injury when administered shortly before or after an intracerebral injection of N-methyl-D-aspartate. However, in this study we report that in perinatal rats if MK-801 (1 mg/kg) is administered intraperitoneally 24 h prior to a unilateral intrastriatal N-methyl D-aspartate injection, N-methyl-D-aspartate-mediated brain injury is paradoxically enhanced. The severity of resulting brain injury is 15-25% greater in groups that received MK-801 in comparison with saline-treated controls (P less than 0.001, linear regression analysis). In contrast, the severity of brain injury resulting from intrastriatal injection of the glutamate agonist quisqualate is not altered by a similar 24 h MK-801 pretreatment. Furthermore, the enhanced toxicity of N-methyl-D-aspartate produced by a 24 h pretreatment with MK-801 is completely blocked if a second dose of MK-801 is administered 15 min after the intrastriatal injection of N-methyl-D-aspartate. To determine if MK 801 produced alterations in glutamate receptor pharmacology co-incident with the enhanced toxicity of N-methyl-D-aspartate, in vitro quantitative autoradiography for excitatory amino acid receptor subtypes was performed with [3H]glutamate and [3H]N-1-(2-thienyl)cyclohexyl-3,4-piperidine in seven-day-old rats killed 2 or 24 h after MK-801 (1 mg/kg) administration. A 2 h MK-801 pretreatment produced a 30 50% increase in [3H]glutamate binding at N-methyl-D-aspartate preferring recognition sites in all four brain regions examined (areas CA1 and CA3 of the hippocampus, corpus striatum, cingulate cortex) in comparison with saline-treated controls (P less than 0.05, ANOVA). [3H]N-1-(2-Thienyl)cyclohexyl-3,4-piperidine binding to the phencyclidine site associated with the N-methyl-D-aspartate receptor was reduced by 60-80% in all brain regions examined (P less than 0.001). Quisqualate-sensitive [3H]glutamate binding was not altered by a 2 h MK-801 pretreatment. In animals that received a 24 h MK-801 pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2255392 TI - Directionally-specific effects of afferent signals from the extraocular muscles upon responses in the pigeon brainstem to horizontal vestibular stimulation. AB - The responses of single units in the brainstem of the decerebrate, paralysed, pigeon were studied. Natural vestibular stimulation was provided by horizontal, sinusoidal, oscillation of the bird and extraocular muscle afferents of the ipsilateral eye were activated by passive eye-movement. Unit responses to vestibular and/or orbital stimuli were examined in sets of peristimulus time histograms interleaved in time. Of 352 units in the brainstem, in the region of the vestibular nuclei, which were exposed to the effects of both vestibular stimuli and passive eye-movement, 40 (11%) responded only to the latter; the other 312 units (89%) responded to vestibular stimulation at 0.4 Hz (amplitude +/ 8 degrees). Of these 312 units, 129 (41%) were affected only by vestibular stimuli; in the other 183 units (59%) passive eye-movement produced clear modification of the vestibular responses by adding excitation or inhibition, or both. There were phasic modifications in most units; in 77 there were longer lasting changes in the vestibular responses, often following a phasic response. In 124 units whose responses were subjected to statistical analysis, the vestibular responses of 42 (34%) were modified only by horizontal eye-movement and eight (6%) were affected only by vertical movement. A further 18% showed larger effects from horizontal than from vertical eye-movement; in 2% vertical eye-movement was preferred. Further examination of the specificity of the effects of eye-movement in planes between the vertical and horizontal was possible in 29 units which showed various degrees of "tuning" of the effect. In some units there was additional specificity for eye-movement in (a) particular directions (towards the beak rather than towards the tail, for example); (b) in particular arcs of the orbit (centre-to-temporal rather than nasal-to-centre, for example). Note that all these effects were upon the responses of the units to horizontal vestibular stimulation. Thus, the modifications of the vestibular responses depended upon specific characteristics of the passive eye-movement. The exact recording sites of 29 units were determined histologically; some were in the medial vestibular nucleus but many were in the adjacent reticular formation. The principal interest of the results is that they provide more detailed information than was available previously on the specificity of the effects of afferent signals from the extraocular muscles upon the vestibular responses of units in regions of the brainstem known to be involved in oculomotor control. The decerebrate pigeon proves to be a particularly good preparation in which to study these effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2255393 TI - High potassium selective permeability and extracellular ion regulation in the glial perineurium (blood-brain barrier) of the crayfish. AB - Selective ion permeability, ion transport properties, and electrical resistance of the perineurial barrier, as they relate to interstitial ion regulation, where studied and characterized electrophysiologically in ion substitution experiments. In high external [K+] a transient spike-like voltage was generated across the perineurial barrier which fell over 1-2 min to a slowly decaying voltage. The glial perineurium had at least a 10 times greater permeability to K+ than Cl-, and was effectively impermeant to Na+. The potential, in high external [K+], was determined by the K+ and Cl- gradients and their relative permeabilities across the sheath. For other cations the selectivity sequence of the perineurial barrier, as determined from electrophysiological measurements, was K+ greater than or equal to Rb+ much greater than NH4+ greater than Cs+ greater than Li+ greater than Na+ corresponding most closely to the Eisenman sequence IV. The perineurium had a resistance of 260 +/- 23 omega cm2 in crayfish physiological solution. In high [K+]0 the resistance fell by over half during the transient spike potential and then recovered towards resting levels as the voltage decayed. In the intact nerve cord interstitial [K+] rose to only 10-20 mM during a 2-min exposure to 100 mM K0+. K influx and efflux were related to the change in barrier permeability and an increased selectivity to K+ which, in these studies, was determined primarily by its electrochemical gradient across the perineurial barrier. The results suggest that the crayfish perineurium is a leaky epithelium capable of a high degree of ion regulation. Trans-perineurial barrier potential and conductance in high external [K+] are primarily functions of passive processes of the perineurial glial cell membranes and of the paracellular conductance channels driven by the electrochemical gradient for the K+. Accordingly, the mass transport of [K+] showed the same quantitative relationship in both directions. PMID- 2255394 TI - Calcium-dependent regulation of potassium permeability in the glial perineurium (blood-brain barrier) of the crayfish. AB - The physiological basis of the high selective potassium permeability of the crayfish glial perineurium was studied. The transient spike-like perineurial potential generated in high external [K+] was used as a measure of barrier K+ permeability. The medial giant axon membrane potential was used to monitor interstitial [K+]. Perineurial current-voltage relations of the perineurium were used to measure electrical resistance and to determine changes in K+ conductance of the perineurial barrier. Of a range of cations studied only Rb+, in addition to K+ generated a large transient sheath potential. In some experiments "regenerative" multiple spikes were observed during the continued exposure of the perineurium to high [Rb+]0. This degree of ion selectivity is typical of glial cell membranes and K channels. Barrier conductance increased only very briefly in Rb+; the potential falling rapidly to a steady 5-10 mV. The PCl/PRb and the PCl/PK ratios at the peak transient potential were similar suggesting the permeability site for these cations was the same. The permeability of Rb+ in the plateau phase was significantly lower than K+ suggesting that high [Rb+]0 may act to block K+ channels. The K(+)-selective permeability was reversibly blocked by extracellular Ba2+ at both the peak and the plateau phase, in a concentration dependent manner. Other K-channel blocking agents, tetraethylammonium ions (10 mM), caesium ions (20 mM), and 3,4-diaminopyridine (0.5 mM) were ineffective. The effect of Ba2+ on the peak potential was similar to the removal of external Ca2+ or exposure to the Ca2(+)-channel blockers, verapamil (10(-4) M) or La3+ (5 mM). The time- and concentration-dependent reversible block of the K+ permeability of the perineurium was consistent with the known action of these agents on voltage gated Ca2+ channels in nerve and glia. La3+ caused an irreversible decrease in perineurial conductance and K+ influx. Lanthanum titration of the negative charges of glial membranes and mucopolysaccharide matrix of the intercellular space suggest they may be important factors in determining the magnitude of the perineurial leak and paracellular K+ permeability. Electron microscopic examination of La3+ distribution demonstrated a diffusion barrier at the outer layer of perineurial glia. The binding of La3+ at the basolateral membranes of the glial barrier suggested this was the site at which La3+ had its physiological actions. The results suggest that the increase in glial membrane K+ conductance in high [K+]0 was most likely due to voltage-gated Ca2+ and K+ channels and Ca2(+)-activated K+ channels of the membranes of perineurial glia. PMID- 2255395 TI - Light inhibits the release of both [Met5]enkephalin and [Met5]enkephalin containing peptides in chicken retina, but not their syntheses. AB - The levels of native and cryptic [Met5]enkephalin in the chicken retina were found to vary during a 12:12 h light-dark cycle, both rising in the light and falling during the dark. Such variations could conceivably arise from (a) changes in the rate of release and subsequent degradation of native and/or cryptic [Met5]enkephalin, (b) changes in the rate of proenkephalin A synthesis, or (c) changes in the rate of proenkephalin A processing. Measurement of the rate of release of native and cryptic [Met5]enkephalin in vitro indicated that the increased rate of release of both of these forms of [Met5]enkephalin during the dark quantitatively accounted for the fall in their retinal levels during the dark. This indicated that the biosynthesis of proenkephalin A was not activated during the light-dark cycle. Molecular weight fractionation of retinal extracts also supported this idea, since the pool of high molecular weight precursors did not vary in size, suggesting that processing was not modulated during the light dark cycle. Instead, the fall in both cryptic and native [Met5]enkephalin during the dark was due to their increased rate of release together with a rate-limiting conversion of high molecular weight [Met5]enkephalin-containing peptides to low molecular weight [Met5]enkephalin-containing peptides. The enkephalinergic cells of the retina seem to cope with physiological variations in demand by accumulating a large pool of peptide during periods of low stimulation (light), so that when stimulation and release is high (dark), the decrease in pool levels does not compromise the function of the cells and their postsynaptic targets. PMID- 2255396 TI - Microtransplantation of neural cells into adult rat brain. AB - Epithelioid ("type 1") astrocytes and hippocampal neurons have been stereotaxically grafted into adult rat brain by a new "microtransplantation" method and the results of grafting assessed at various survival times by conventional histological methods using light and electron microscopes. The extent of bleeding that accompanied grafting was assessed by peroxidase staining of extravascular red cells. Grafts were small, compact and reproducible in terms of their volume and location. Implantation was achieved with very little trauma to host tissue. There was no apparent disruption of host tissue adjacent to the graft and very little damage to host blood vessels from earliest survival times. Donor astrocytes were in direct contact with cells of the host immediately after grafting. This situation was compared with conventional implantation of astrocytes in which much damage, necrosis and bleeding occurred and for which cells of graft and host were initially isolated from one another. Microtransplanted astrocytes were observed to migrate. Similar, comparatively non traumatic microtransplantation of hippocampal neurons was also carried out. Long term survival of grafted neurons was demonstrated. PMID- 2255397 TI - Chronic effects of the selective serotoninergic neurotoxin, methylenedioxyamphetamine, upon cerebral function. AB - The amphetamine derivative methylenedioxyamphetamine selectively destroys serotoninergic terminals in the brain. We have studied the effects of this toxin upon resting cerebral function, as reflected in rates of glucose utilization. Rats were injected subcutaneously with either 1 ml/kg saline (n = 5) or 20 mg/kg methylenedioxyamphetamine (n = 5) twice daily for four days. Local cerebral glucose utilization was measured between six and nine weeks after treatment using [14C]2-deoxyglucose quantitative autoradiography. Samples of frontal cortex taken from these animals for in vitro [3H]paroxetine binding showed a 64% reduction in 5-hydroxytryptamine uptake sites. In the majority of the 31 functionally diverse brain areas analysed, no significant changes were measured, but significant (P less than 0.05) increases in glucose use were found in neocortical regions e.g. anterior cingulate cortex (+16%) and sensorimotor cortex (+21%). However, the most profound increases were found in globus pallidus (+30%) and hippocampus molecular layer (+34%). It would appear, therefore, that treatment with methylenedioxyamphetamine results in long-lasting alterations in cerebral functional activity. PMID- 2255398 TI - No effect of pulsed magnetic stimulation on the blood-brain barrier in rats. AB - The impact of transcranial pulsed magnetic stimulation on blood-brain barrier permeability was studied in rats. An integral uptake technique was used to asses the blood-brain barrier permeability to the tracers [3H]sucrose, [14C]urea, and 36Cl-. From the arterial plasma concentration-time curve-integral the permeability surface-area products were calculated. A Dantec magnetic stimulator delivering a peak magnetic field of 1.9 T with a rise-time of 160 microseconds was used for transcranial stimulation of the rats. One group of rats had about 50 60 stimulations during the 15-min infusion of the tracers while another group was exposed to 50 magnetic stimulations a day for one week. A third group comprised the controls. No differences in permeability surface-area product were found for any of the three tracers in the rats exposed to magnetic stimulation as compared with the controls. It is concluded that with regard to blood-barrier integrity, pulsed magnetic stimulation of the brain can be regarded as safe. PMID- 2255399 TI - Postnatal development of the T calcium current in cat thalamocortical cells. AB - The burst firing of thalamic cells in the adult cat is mainly controlled by a voltage-dependent membrane current that has recently been characterized as being similar to the low voltage-activated (i.e. low threshold), T-type, Ca2+ current originally described in sensory neurons. In those neurons so far studied, as well as in skeletal muscle, the low threshold Ca2+ current has been shown to decrease in amplitude or even disappear during embryogenesis or the first few weeks of postnatal life. We have now investigated the in vivo postnatal development of the low threshold Ca2+ current present in thalamocortical cells of the dorsal lateral geniculate nucleus of cats aged four to 100 days. The results show that the amplitude of the low threshold Ca2+ current triples from 0.5 nA in the first few days after birth to over 1.5 nA in the adult. However, this increase in amplitude is not accompanied by any change in its inactivation and activation properties, its latency to peak and the time dependence of inactivation removal. Because of these similarities during development and in adulthood it is likely that a major role of the low threshold Ca2+ current during neuronal development is the generation of oscillatory activities similar to those observed in adult thalamocortical cells. PMID- 2255400 TI - Regional distribution of cholecystokinin binding sites in macaque basal ganglia determined by in vitro receptor autoradiography. AB - Cholecystokinin binding sites were labeled with [3H]cholecystokinin-8, [125I]cholecystokinin-33, and [125I]cholecystokinin-8 in major structures of macaque basal ganglia by in vitro receptor autoradiography. Analysis of autoradiograms revealed areas of heavy cholecystokinin binding in the neostriatum and substantia nigra that were set off, often quite sharply, from the adjacent globus pallidus and subthalamic nucleus where labeling was, by contrast, very light. Heavy label characterized the ventromedial and posterior parts of the caudate nucleus and adjacent putamen, binding was of moderate intensity in central areas of these regions, while, the dorsolateral margin of the head of the caudate and precommissural putamen, the dorsolateral one-third of the body of the caudate, and all but the most medial and ventral portions of the posterior putamen lateral to the pallidum were sparsely labeled. The pattern of cholecystokinin binding within the neostriatum was mottled; patches of reduced label stood out from the background of more prominent binding. However, those patches were only imperfectly correlated with the striosomal organization of both the caudate nucleus and putamen as revealed by acetylcholinesterase staining. Cholecystokinin binding in the substantia nigra was also intricately patterned. Moderately dense, vertically orientated bands of label were found in the dorsal one-third to half of the pars reticulata, providing a marked contrast to the near background levels in the ventral pars reticulata and overlying pars compacta. The present study shows that heavy cholecystokinin binding is confined to particular areas within the primate basal ganglia; the pattern of label within the substantia nigra and neostriatum can be linked to intrinsic and afferent connections of these structures. The confinement of binding sites to the dorsal pars reticulata suggests an association with dendrites of pars compacta neurons which invade this region; this interpretation is consistent with recent evidence of depletion of nigral cholecystokinin binding sites in macaques following chemical lesion of dopaminergic cells of the par compacta. In the neostriatum the distribution of binding shows overlap with its topographically organized corticostriatal innervation; portions of heavily labeled striatum coincide with regions innervated by association cortex of the frontal and temporal lobes, whereas regions of diminished binding correspond to areas innervated mainly by sensory and motor cortex. These latter findings suggest that cholecystokinin may have a particularly strong influence on cognitive aspects of striatal function. PMID- 2255401 TI - Memory deficits following nucleus basalis magnocellularis lesions may be mediated through limbic, but not neocortical, targets. AB - In order to test the contribution of the target areas of the nucleus basalis magnocellularis to the mediation of item and order recognition memory for spatial locations, one set of rats received lesions of the dorsolateral frontal cortex, parietal cortex, or basolateral amygdala after training in an order recognition memory task, whereas another set of animals received lesions of the nucleus basalis magnocellularis or basolateral amygdala in an item recognition memory task. Animals with basolateral amygdala lesions displayed a deficit for order recognition memory, but no deficit for item recognition memory, a pattern equivalent to that found for animals with nucleus basalis magnocellularis lesions. In contrast, animals with dorsolateral frontal cortex displayed no deficit, and animals with parietal cortex lesions displayed only a partial deficit for order recognition memory, results that differ from those found for animals with nucleus basalis magnocellularis lesions. It appears that the nucleus basalis magnocellularis influences item and order recognition memory for lists of spatial locations primarily through projections to limbic but not neocortical targets. PMID- 2255402 TI - Intraluminal Miller-Abbott tube stenting as treatment and prophylaxis of recurrent intestinal obstruction. AB - Chronic recurrent intestinal obstruction due to massive adhesions after abdominal surgery is a complication that is difficult to treat. The records were studied of 25 patients with acute intestinal obstruction due to massive adhesions. Since conservative measurements were unsuccessful, the patients were treated with internal intestinal splinting by means of a Miller-Abbott tube. These 25 patients underwent a total of 72 operations, 36 were performed for mechanical obstruction. Conservative treatment alone was effective during 25 admissions. The complaints of the patients lasted five years on an average. After lysis of adhesions the Miller-Abbott tube was introduced either via the nose, via a gastrostomy or via an enterostomy. The tube was left in situ for three weeks and then gradually withdrawn. There was no hospital mortality. There was one postoperative complication: a tube had to be removed under general anaesthesia. Long-term follow-up of the patients varied from 4.5 to 19 years with a mean of 11.3 years. One patient with recurrent intestinal obstruction due to adhesions, required surgical intervention after one year. A second patient with Peutz-Jeghers syndrome needed surgery because of an intestinal adenoma after six years. The mean symptom-free interval was 11.1 years in the cured patients. PMID- 2255403 TI - Transscaphoid perilunate fracture dislocation and pseudarthrosis of the scaphoid. AB - The results of conservative treatment of a perilunate fracture dislocation were retrospectively studied. In six patients, the treatment consisted of closed reduction and immobilization in a below the elbow cast for 12 to 16 weeks. Five patients had a compromised healing of the scaphoid fracture. The frail vascularization of the scaphoid, extensive ligamentous injury and possible mid carpal instability in case of perilunate fracture dislocation as well as a non anatomical reduction of a scaphoid fracture are causative factors in ensuing scaphoid pseudarthrosis. If anatomical reduction of a perilunate fracture dislocation cannot be obtained, open reduction and internal fixation should be considered. This will offer the scaphoid the best chance at fracture healing and will restore the stabilizing function on the mid carpus. PMID- 2255404 TI - The unreduced carpal dislocation: a concept of treatment. AB - The treatment of unreduced carpal dislocations and fracture dislocations is controversial. To obtain reduction, an extensive surgical soft-tissue dissection is usually required. The accompanying damage to vessels, ligaments and articular cartilage increases the risk of symptomatic arthritis of the wrist. To avoid this complication as much as possible, a closed technique of treatment has been developed. The method consists of radiocarpal distraction with an external fixator followed by percutaneous reduction and immobilization with the same external fixator. In five out of six patients with an unreduced carpal dislocation this method appeared successful. PMID- 2255405 TI - Traumatic posterior luxation of the hip. AB - The long-term outcome of treatment of posterior hip dislocations was studied in 60 patients. Thirty-two patients had concomitant fractures of the acetabular rim and seven had also femoral head fractures. Treatment consisted of immediate reduction, followed by gentle traction during one week and progressive weight bearing over six weeks. Thirteen patients needed internal fixation of the acetabular fracture. Fourty-six patients could be followed for a median of 6.5 years. Fifteen patients, all with associated fractures, had late complications: peri-articular ossifications (5), avascular necrosis of the femoral head (1), mild osteo-arthrosis (5) and pain of unknown origin (4). No complications were noted in patients with simple posterior dislocation of the hip. Simple traumatic posterior hip dislocation has an excellent prognosis. Poor results only occur in case of associated fractures. PMID- 2255406 TI - Friedrich's disease. AB - Three patients are reported with Friedrich's disease, a rare deformity of the sternoclavicular joint. This clinical entity is a symptomatic expression of osteonecrotic changes of the medial inferior border of the clavicle, with a still unknown pathogenesis. In our own experience and according to that of others, conservative treatment for this rare condition may be advisable. PMID- 2255407 TI - Intra-uterine testicular torsion. AB - Two cases of intra-uterine testicular torsion of the intravaginal type are presented. Orchiectomy of the affected testicle and contralateral orchidopexy were performed in both cases, followed by an uneventful postoperative course. Classification, clinical presentation, pathogenesis and treatment are discussed. PMID- 2255408 TI - [Role and evolution of imaging in medical radiodiagnosis]. PMID- 2255409 TI - [CA 15-3 associated with CEA and TPA in the follow-up of breast carcinoma]. AB - The serum level measurement of CA 15-3 antigen was evaluated in association with CEA and TPA, during the follow-up in mastectomized patients previously affected by breast cancer: 94 patients with metastases and 319 without apparent disease evolution. In the group of patients with metastases, the CA 15-3 antigen showed high sensitivity (70.2%). The CA 15-3 and TPA association increased the sensitivity (87.2%), while the CEA and CA 15-3 association did not increase this parameter. All markers showed good correlation with therapeutic response. Thirteen patients among 19 without apparent disease evolution, developed metastases, during the follow-up. The CA 15-3 and/or TPA increase allowed to predict disease progression in 13/13 cases, 2-10 months before clinical evidence. Our experience shows that CA 15-3 measurement associated with TPA, during the follow-up of patients affected by breast cancer, may be helpful for increasing the predictivity with respect to those patients most likely to develop recurrent disease. PMID- 2255410 TI - [Tag 72: a new tumor-associated antigen identified by a monoclonal antibody]. AB - In order to evaluate the usefulness of Tag 72--tumor associated antigen assay--in gastroenterology, we have studied with Ca 72-4 radioimmunoassay (Centocor) 551 patients suffering benign (233) and neoplastic (318) gastrointestinal diseases and 205 normal controls. The cut-off point was fixed at 6 U/ml. Only in gastric cancers, the Tag 72 assay, with the proposed method, provide additional information in this pathology (sensitivity 30%, specificity 98.7%). The most striking observation to be made from the current study is a poor sensitivity of the test for gastrointestinal cancers, but rather the excellent specificity of the Ca 72-4 IRMA with respect to benign gastrointestinal diseases. The sensitivity of Ca 72-4 assay, vs Ca 19-9 and CEA, for the same diseases, is less, but specificity is better. PMID- 2255411 TI - [Diagnostic and prognostic value of CEA and GICA in colo-rectal tumors. A caseload contribution]. AB - The Authors analyse the clinical usefulness of serum levels' determination of Carcinoembryonic Antigen (CEA) and Gastrointestinal Cancer Antigen (GICA) in 152 patients with colorectal cancer, admitted to their Hospital from November 1982 to March 1989. The sensibility for primary diagnosis of each tumor marker is not very high but there is a relationship between the stage and the histological characters of the disease, especially when the markers are considered at the same time. Preoperative serum level determination of CEA and GICA can be considered a good prognostic index: infarct the increase of the levels is generally due to metastatic tissue or local recurrence. This was confirmed during patients follow up by further tests which revealed recurrence of the disease. PMID- 2255412 TI - [The importance of glycosylated plasma protein determination in the diagnosis of carbohydrate intolerance in obesity]. AB - To evaluate the possible interest of the dosage of glycated plasma proteins in the diagnosis of glucidic intolerance, OGTT with determination of glycaemia and insulinaemia, HbA1c and fructosamine was determined in 6 normal and 35 obese subjects. On the basis of OGTT the subjects were subdivided into 20 obese with normal glucose tolerance, 7 with IGT and 8 with DM. In the comparison between all the subjects there was a significantly higher plasma fructosamine concentration in the obese with DM (p less than 0.001). No difference was noticed between the normal subjects and the other two classes of obese patients. This suggests that the evaluation of glycated plasma proteins is scarcely sure in a screening plan. PMID- 2255413 TI - [Stage classification of chronic lymphatic leukemia. A retrospective analysis of 263 cases]. AB - We have analyzed 263 consecutive patients with chronic-lymphocytic leukemia. They all have been studied according to five different staging systems respectively proposed by Rai (1975), Binet (1977), Binet again (1981), Baccarini (1982) and Rozman (1984). All these procedures proved to be effective, because they divided our cases in groups with significant differences in survival time. The paper displays features and usefulness of each staging system. PMID- 2255415 TI - [Possible correlations between histopathologic morphology and prognosis in gastric carcinoma]. AB - Possible correlations between histological aspects and prognosis of gastric cancer are discussed. The influence of classical histological morphology and the classifications of Lauren and Ming are re-examined in the light of international literature and it is concluded that the histological study of the tumours based on the type of biological growth would seem to offer better prognostic indications. PMID- 2255414 TI - [Role of endoscopy in lymphomatous pathology of the digestive tract]. AB - Increasingly frequent reports of lymphoma with a gastro-intestinal primary location have stimulated much interest. Symptomatology has been shown not to be very specific, and scarcely different to that of other gastro-intestinal pathologics, both benign and malignant. The identification of some endoscopic pictures which suggest a lymphomatosic pathology and the possibility of collecting targeted biopsy samples, have placed endoscopy among the most important tests in the diagnostic and staging phase of gastro-intestinal lymphoma. This technique plays an equally important role in the follow-up period, since it allows the therapeutic efficacy of treatment to be assessed and the early identification of possible relapses. PMID- 2255416 TI - [Evaluation of the effects of thymopentin on the incidence of leucopenia in patients treated with chemotherapy for breast carcinoma]. AB - Random additional treatment with Thymopentine was administered to a group of 46 mastectomised women in order to assess its possible anti-leucopenic efficacy in relation to cytotoxicity caused by anti-blastic drugs. Results reveal a certain degree of efficacy in reducing the incidence of leucopenia when treatment was administered continuously from the start to the end of chemotherapy. This aspect plays an extremely important role in avoiding the protraction of the normal interval between one cycle of anti-blastic chemotherapy and the next. PMID- 2255417 TI - [Electrogustometry. Presentation of a new electrogustometer]. AB - A new electrogustometer containing variations dictated by clinical practice is presented. Technical innovations are presented and discussed together with application of the technique in the study and prognostic assessment of peripheral paralysis of the facial nerve. Some results obtained in clinical practice in the same pathology with different aetiology are discussed. PMID- 2255418 TI - [Churg-Strauss syndrome: is it a rare disease?]. AB - We describe four patients with Churg-Strauss syndrome admitted to the hospital in 1988. Some clinical and histological features of particular relief are present in these cases. All patients had been treated with corticosteroids and they are now in remission. Our work suggests that Churg-Strauss syndrome is not a rare disease and that an early diagnosis and appropriate therapy may influence favourably at least long term survival. PMID- 2255419 TI - [Pulmonary involvement in a case of CREST syndrome]. AB - The paper describes the clinical, X-ray and functional aspects of lung involvement in a case of CREST syndrome, a variant of systemic sclerosis. The characteristic signs of the disease were associated in this patient with lung involvement in the form of widespread interstitial fibrosis complicated by the presence of alveolar cysts in the lower lobes. The state of severe chronic respiratory insufficiency was the most unfavourable factor in the prognosis for this patient, in particular in the light of the disappointing response to corticosteroid therapy. PMID- 2255420 TI - [Description of a case of rheumatoid pleuropneumopathy with primary onset]. AB - A case of pleuropulmonary manifestation as the first symptom of rheumatoid arthritis is reported; articular involvement followed at a later stage. Pleuropulmonary localisation of rheumatoid arthritis is varied and infrequent; it is seldom the first manifestation of illness. This case was particular because isolated pleuropulmonary symptom appeared in a subject negative rheumatoid factor. The patient improved after initial NSAIDS treatment, followed by corticosteroids and NSAIDS together, leading to the resolution of clinical and x ray symptoms. PMID- 2255421 TI - [Clinical and diagnostic considerations on degenerative spino-cerebellar diseases. A clinical and instrumental description of 2 cases]. AB - Two cases of spino-cerebellar heredoataxia are reported. The first patient, aged 18, presented the clinical peculiarities of Friedreich's disease; subjected to encephalic CT and encephalomedullary NMR the proved normal; EMG study and visual, acoustic and somatosensorial evoked potentials were not normal but there was nothing specifically wrong. The second patient, aged 30, followed up for more than 10 years, presented the clinical aspects of Pierre Marie disease; stress is laid on encephalic CT examinations carried out at the age of 20 and 30. These were pathological due to the marked dilatation of the IVth ventricle and the basal cisternae; evoked potential changes were aspecific. The nosography is discussed, especially as regards clinical diagnosis, in the absence of typical neuroradiological or other instrumental aspects and, obviously, in the absence of anatomopathological signs. PMID- 2255422 TI - [Neuralgic amyotrophy. A clinical and neurophysiologic longitudinal study of 3 cases]. AB - The Authors describe three cases of neuralgic amyotrophy examined clinically and neurophysiologically at the onset of symptoms and after six months. At that time patients showed an objective improvement in strength and functions, though a few SEP and EMG alterations persisted. These findings are considered of out discrepancy between clinical and neurophysiological picture. PMID- 2255423 TI - A review of screening instruments for assessing cognition and mental status in older adults. AB - Older adults in non-psychiatric acute and long-term care settings need to be screened routinely for cognitive function and mental status by clinicians and health care providers. Screening instruments increasingly are being used in order to evaluate programs, implement clinical decisions and conduct research. The purpose, scope and depth of needed assessment guides the selection of the screening instrument. This article critically reviews 11 screening instruments used to assess cognitive function and mental status in older adults: Dementia of the Alzheimer Type Inventory, Brief Cognitive Rating Scale, Blessed Dementia Scale, Cognitive Capacity Screening Examination, Cognitive Levels Scale, FROMAJE, Global Deterioration Scale, Mini-Mental State Exam, Clinical Dementia Rating, Mental Status Questionnaire and the Short Portable Mental Status Questionnaire. Since cognitive impairment is a broad construct, the descriptors used to search the literature were the following: age-associated memory impairment, acute confusional states, Alzheimer's disease, cognition, confusion, delirium, dementia, mental status, multi-infarct dementia, Pick's disease, primary degenerative dementia, pseudodementia and senile dementia of the Alzheimer's type. The Brief Cognitive Rating Scale and the Dementia of the Alzheimer Type Inventory are the only two instruments capable of distinguishing Alzheimer's from other dementias, and the CDR is the only instrument that assesses hobbies. PMID- 2255424 TI - Comparing two sampling techniques for endocervical cell recovery on Papanicolaou smears. AB - The importance of endocervical cells in a Pap smear is well-recognized. A Pap smear lacking endocervical cells is considered inadequate and necessitates a repeat test. Clinicians continue to search for techniques that will ensure consistently adequate samples. In this study, Pap smears were obtained for 200 subjects, alternating use of a saline-moistened cotton-tipped applicator with the Zelsmyr Cytobrush for endocervical cell collection. Endocervical cells were present in all 100 Cytobrush smears, compared with 91 of the cotton-tipped applicator smears. The difference is significant (p less than 0.005). The nine smears that lacked endocervical cells were repeated, using the Cytobrush; all nine repeat smears contained endocervical cells. Although the sample used in this study was small, results indicate that the Cytobrush is more effective in obtaining endocervical cells than the cotton-tipped applicator. Use of the Cytobrush is recommended in the interest of reducing the number of false negative reports. PMID- 2255426 TI - HIV. Negative images. PMID- 2255425 TI - Assessment and management of hypothyroidism. AB - Hypothyroidism is a hypoactive metabolic state associated with a deficiency in thyroid hormone metabolism. This condition affects many bodily systems, including the nervous system, circulatory system, muscular system, the heart and energy producing system, and the endocrine glands. The goal of treatment for this hypometabolic state is replacement of thyroid hormones. Health care practitioners need to be aware of early signs and symptoms, and subsequent treatment and monitoring of patients with hypothyroidism. PMID- 2255427 TI - HIV. A united approach to care. PMID- 2255428 TI - HIV. A bleak inheritance. PMID- 2255429 TI - Nursing at the Nuffield. PMID- 2255430 TI - Education. Out of the frying pan.... PMID- 2255431 TI - AIDS: the part nurses can play. PMID- 2255432 TI - Positive health. PMID- 2255433 TI - Nursing abroad. Piekny Polska. PMID- 2255434 TI - Care for all. PMID- 2255435 TI - Surfact of life for pre-term babies. PMID- 2255436 TI - She who dares, wins. PMID- 2255437 TI - HIV. Banishing prejudice. PMID- 2255438 TI - Catheter care. Working together for continence. PMID- 2255439 TI - Catheter care. Standards of excellence. PMID- 2255440 TI - Daphne Parish: nursing freedom. Interview by Mark Allen. PMID- 2255441 TI - Health promotion. The devil and the deep blue sea. PMID- 2255442 TI - Nursing abroad. Swaziland, a country of tradition and beauty. PMID- 2255443 TI - The Darlington assurance. PMID- 2255444 TI - The message in the bottle. PMID- 2255445 TI - Mismatched bone marrow transplants. PMID- 2255446 TI - Wordly wise. PMID- 2255447 TI - Nurses and doctors join forces to beat the 'dreaded disease'. PMID- 2255448 TI - Elements of misinformation. PMID- 2255449 TI - A change for the better. PMID- 2255450 TI - A day in the life.... PMID- 2255451 TI - Catheter care. An internal approach. PMID- 2255452 TI - Factors associated with development of diabetes mellitus: results from a cross sectional survey in Kawerau. AB - To determine risk factors for diabetes mellitus, a cross sectional study was performed on adult residents of Kawerau. Three thousand nine hundred and eighty two adults (82.8% response rate) had a fructosamine screening test and undiagnosed diabetes was confirmed in 29 cases. Controls were 241 nondiabetic individuals randomly selected from residents with normal fructosamine result. Compared with controls, new diabetics were significantly older and more obese (p less than 0.05). After controlling for age and body mass index, we also found significant increases in systolic and diastolic blood pressure, 2 hour insulin, and fasting triglyceride levels. These results suggest that the above variables are associated with diabetes mellitus independent of age and obesity. PMID- 2255453 TI - Evaluation and outcome of the vision screening programme in south Auckland intermediate schools. AB - Four thousand, seven hundred and fifty-nine form 1 intermediate school children (aged 11 years) in the south Auckland health district were screened in 1987. There were 88 (1.8%) new visual defects detected (defined as a visual acuity (VA) of 6/12 or worse in one or both eyes), while 103 (2.2%) wore glasses and a further 22 (0.5%) did not have their glasses available at the time of the VA test. The total prevalence of screening visual defects was 4.5%. A survey was carried out of those pupils who failed the VA screening test in the previous year and those recorded as wearing glasses. Sixty-seven (76%) of 88 children with newly detected visual defects were interviewed. An abnormal VA test was confirmed in 59 (88%), of which 39 (66%) required treatment. Thirty were prescribed glasses, of which 27 purchased them, but at the time of interview nine did not have them available. Twenty-one (20%) of the 103 children tested with glasses failed the VA test. Twenty-two children had glasses but were not wearing them at the time of the VA test. Only three of these children had a VA better than 6/12 bilaterally. These results highlight the importance of the vision screening programme in this age group and the follow up of children with known visual defects. PMID- 2255454 TI - Falls, fractures and drugs. PMID- 2255456 TI - Neighbourhood of domicile and hospital admissions in Auckland: is there a relationship? AB - The relationship between the health and equity index of socioeconomic status/need and hospital admission rates has been investigated. The index is based on an area's population characteristics, and has previously been used for determining service provision and to describe an area's health need. This study demonstrates a strong positive correlation (r = 0.88, 95% confidence intervals 0.75 to 0.94) between the index and standardised hospital admission rates in the Auckland urban area. This association validates the index as a proxy for morbidity, in as much as hospital admission rates measure morbidity, and supports suggestions for its use to alter interregional and intraregional resource allocation. PMID- 2255455 TI - No new evidence on the cervical cancer study. PMID- 2255457 TI - General practitioners' ability to predict outcome for elderly patients admitted to acute medical beds. AB - This study investigated general practitioners' expectations about the management of their elderly patients following admission to acute medical beds. They were asked to predict the length of stay, main type of hospital care and outcome of the admission. There was very poor agreement between the predicted and the observed length of stay, type of care and outcome. The general practitioners underestimated the length of stay and severity of outcome, and overestimated the amount of acute medical intervention patients would receive in hospital. These results suggest that there is an urgent need to improve the level of communication between general practitioners and secondary care services. PMID- 2255458 TI - Cot deaths in Canterbury: the pattern over twenty years. PMID- 2255459 TI - The Marlborough hepatitis B survey. PMID- 2255460 TI - Remarkably small melanomas. PMID- 2255461 TI - Melanoma and polyunsaturated fats. PMID- 2255462 TI - Hip fractures and fluoridation. PMID- 2255463 TI - Patients are patients. PMID- 2255465 TI - McArthur vs Medical Council. PMID- 2255464 TI - Resources for prevention of cardiovascular disease. PMID- 2255466 TI - Steroids and acute spinal injury. PMID- 2255467 TI - AIDS. PMID- 2255468 TI - Office parties--employers beware. PMID- 2255469 TI - Screening. OH can profitably contract out. PMID- 2255470 TI - Stress in life and work. Part 3: Organisational factors (1). PMID- 2255471 TI - Leber's optic atrophy. PMID- 2255472 TI - [Methods to improve the delivery of hospital ophthalmological care to children in the Ukrainian SSR]. AB - On the material of Children Eye Department the Filatov Institute, changes in the structure of eye pathology for the period of 1947-1989 are analysed. It is shown that for the last years, among all eye diseases, the incidence of inflammatory eye diseases fell to 7.5%. The incidence of eye traumas and their outcomes reaching 26.2% remained stable. The incidence of congenital pathology (35.4%) and new-formations in the eye (10.8%) with predominance of malignant tumors, complex pathology of oculomotor apparatus (23.5%) reached high values. Organization of centers, of ophthalmic microsurgery in children allowed to introduce into ophthalmological practice complex surgical interventions requiring special devices and instruments. Surgical activity of the Center of Ophthalmic microsurgery in Children on the basis of the Filatov Institute made up 84.5% in the last five years. In order to optimize the rendering of stationary ophthalmological aid to children, the authors consider it necessary to improve continuity between a microsurgical center and regional children eye hospitals, to increase qualification of children ophthalmologists, to create a Republic Center for Rehabilitation of Children with eye diseases on the basis of a sanatorium with a good ophthalmological equipment. PMID- 2255473 TI - [The organization of work in the pediatric department of an urban ophthalmologic hospital]. AB - The paper analyses the work of a children ophthalmological department and of a centre of microsurgery in children created on its basis, that are attributed to the structure of the town ophthalmological clinical hospital in Kharkov. The paper presents data on the structure of eye pathology, surgical activity (it makes up 60%), suggestions for optimizing the work of the department. A positive role in optimization of work in children department is its belonging to a big ophthalmological hospital. This allows to widely use for children the whole store of diagnostic means, different surgical equipment, other technical means. Of importance is a permanent contact with the chair of children ophthalmology, enrollment of physicians into research work, constant improvement of their skill. PMID- 2255474 TI - [Improvement of ophthalmologic care for children at polyclinics]. AB - On the basis of a long-term experience of work of the Children Ophthalmologic Service in Moscow negative aspects of organization of the ophthalmologist's work in the children town polyclinic are shown, and arguments are presented in favor of a proposition to organize an ophthalmologic polyclinical department in basic children polyclinics with introducing medical nurse optometrists [correction of nurses-opticometrists] into the staff of children polyclinics. "A Provisional Statute of a Children Dispensary Polyclinical Department" and a scheme "The Structure of a Children Ophthalmologic Union (Regional, Town, District)" are subjoined. PMID- 2255475 TI - [Some characteristics and aspects of a pediatric eye service]. AB - The authors share experience of organization of work in the children ophthalmological service in Krivoy Rog and adjacent countryside. The work in the Center of Eye Protection in Children is analysed, and the structure of Children Ophthalmological Service in a big industrial town is subjoined. Attention is drawn to a primary link of Children Ophthalmological Service--an eye room of a territory hospital, a central district hospital, divisional pediatric, preschool and school networks. Arguments are presented concerning essential influence of correct organization of work of this link on effectiveness of dispensarization of children with eye pathology. A question is raised about the necessity to consolidate the primary link of Children Ophthalmological Service, the lacking of which cannot make the whole system of children ophthalmological aid to be of full value. PMID- 2255476 TI - [The adaptation of children with eye diseases to treatment in the hospital]. AB - Results of observation over 120 children with different eye diseases (60 boys and 60 girls), aged from 4 to 15 years, are analysed considering individuality of their character. By the character of adaptation to hospital conditions, all children were divided into three groups: those with good and quick adaptation, with bad adaptation, and with intermediate character of adaptation. A number of regularities have been revealed that allow to highly organize psychoprophylactic work with children in the hospital considering the character of their adaptation to hospital conditions. Recommendations are given for facilitating the children's stay of each group in the hospital in the period of treatment. PMID- 2255477 TI - [The clinico-morphologic foundation of the modern pathogenetically oriented surgery of hydrophthalmos simplex]. AB - On materials of 45 biopsies dissected at the time of antiglaucomatous operations and 10 eyes of newborns, a detailed morphologic analysis of the state of the drainage apparatus of the in norm and at relatively early stages of hydrophthalmos simplex is presented, and considering results of clinical investigations (105 eyes, of them 45 eyes mentioned) a foundation of modern surgery of congenital glaucoma is given. It is shown that the basis of congenital pathology of retinocorneal angle is disturbance of anatomotopographic relationships of its structures as well as expressed trabeculodysgenesis and dysgenesis of scleral sinus. The paper describes three main variants of combinations of pathologic changes in the drainage apparatus, characterized by a common gonioscopic picture and reflecting the degree of severity of congenital pathology (3 degrees of goniodysgenesis). It is noted that the presence of a coarse congenital pathology of trabecular plexus in hydrophthalmus, incompatible with the possibility of its functioning, and at the same time a satisfactory enough state of the "scleral sinus-emissary" link allow to consider the basic element of surgical reconstruction of anterior outflow passage to be trabeculotomy from outside. Indications in the choice of adequate surgical intervention and its volume are shown (the degree of goniodysgenesis and the state of functional preservation of scleral sinus and emissaries). The approved, within 15 years, system of operations in case of hydrophthalmos simplex and their results are presented. PMID- 2255478 TI - [The effect of a pulsed electromagnetic field on the hemodynamics of eyes with glaucoma]. AB - The influence of pulse electromagnetic field (PEMF) on hemodynamics of the eye in open-angle glaucoma has been studied by means of a method and a device proposed at the Filatov Institute. The PEMF characteristics are: impulse frequency--50 Hz, exposition--0,02 sec., impulse shape--square, rate of impulse rise--4.10(4) c rate of magnetic induction rise--2.10(4) mT/c, amplitude value of magnetic induction at the impulse height--9.0--8.5 mT, duration of the procedure--7 min., a course--10 sessions. Observations over 150 patients (283 eyes) with latent, initial and advanced glaucoma have shown a positive influence of PEMF on hemodynamics of a glaucomatous eye: a rise of rheographic coefficient and relative volume pulse in 87,99 and 81,63%, respectively. The degree of the rise and restoration frequency of rheographic values of the glaucomatous eye under the influence of PEMF to the age norm was more expressed at initial stages of the glaucomatous process (latent and initial glaucoma). PMID- 2255479 TI - [A method of surgical treatment of progressive and complicated myopia]. AB - The paper describes a modification of scleroplastic operation combining a vertical bandage with simultaneous covering of posteroexterior segment of the eye ball and creation of a "depo-tissue". As a grafting material, preserved human dura mater was used. By the proposed method, 97 operations were made in 67 patients with myopia from 6.0 to 32.0 D. In 30 patients, the surgical results were observed within 3 years. In all of the patients operated on, the stabilization of the process was recorded. The proposed modification is technically simple and accessible to a wide circle of ophthalmologists. PMID- 2255480 TI - [The effect of the incision in cataract extraction on corneal astigmatism]. AB - Postoperative corneal astigmatism has been studied in 130 eyes after cryoextraction of senile cataract depending in the cataractous incision: perpendicular, step-shaped alone, step-shaped with additional scleral "cap peak", 5 x 3 mm. On discharge, most frequently (in 75% of cases) a direct kind of corneal astigmatism was observed. Astigmatism invariably decreased and became stable after 4--7 months, direct astigmatism became rarer (44%), but the number of eyes with reversed astigmatism increased (40%). The lowest degree of corneal astigmatism (1.8 +/- 16D) and consequently the highest surgical visual outcomes were recorded after a step-shaped incision. PMID- 2255481 TI - [The use of an immunoglobulin in the comprehensive treatment of ophthalmic herpes]. AB - The paper analyses results after treatment of 30 patients with herpetic keratitis by means of a specific antiherpetic immunoglobulin manufactured at the Sverdlovsk Research Institute of Virus Infections. As compared with traditional treatment, the terms of clinical recovery and the number of bed-days reduced. The preparation can be used in a complex treatment of patients with a herpetic disease. PMID- 2255482 TI - [Assessment of individual eye protection devices based on their effect on the frequency-contrast characteristics of the visual analyzer]. AB - Assessment of means for individual eye protection by the method of visocontrastometry, allows, already at the stage of projecting, to determine the correctness of selecting vision glasses by conditions of visual work. Investigations of 3 kinds of goggles: for reindeer breeders of Far North (2 variants), for mechanics and for protection from pesticides have shown that by their influence on frequency-contrast characteristic all they comply with physiologic hygienic demands. The value of the used method of control of the quality of individual eye protection means is established. PMID- 2255483 TI - [A comparative evaluation of contact lens tolerance and the possibilities for its enhancement]. AB - The paper analyses results after examination of 276 patients (495 eyes) with different types of rigid and soft contact lenses. A study of some ways for improvement of contact lens tolerance has shown that improvement of rigid contact lenses can be achieved both by perfection of their construction (in particular by using spherotoric rigid lenses) and with the help of gas-permeable materials (in particular, cellulase acetobutyrate). The improvement of soft lens tolerance can be achieved by reducing the thickness of the lens as well us by using highly hydrophilic gels. If the known methods for improvement of contact lens tolerance fail to be effective, medicamentous preparations (such as solcoseryl, taufon, emoxipin) can be used as a method of choice; their usage is justified in keratoconus of stages II-IV, when rigid lenses are a single kind of optic correction and their tolerance is lowered. PMID- 2255484 TI - [The prevalence of refractive, anisometropic amblyopia in adults without strabismus and with contact lens correction]. AB - The paper presents results after examination of 1260 adults (2547 eyes), aged from 18 to 55 years, for the period from 1982 to 1988. The examination was carried out in order to reveal the incidence of refractive, anisometropic amblyopia without strabismus in persons using glasses (a control group) and contact lenses as well as to determine a degree of spheric, astigmatic refraction in development of amblyopia on the background of contact lenses. It was found that amblyopia on the background of contact correction, as compared with glass correction, develops rarer making up 22.03% of them low degree of amblyopia is recorded in 51,16%, moderate--in 35,65% high--in 13,19% to the total number of amblyopic eyes examined. Direct relationship between the number of amblyopic eyes and degree of astigmatism and anisometropia is revealed. Detection of amblyopia in adults without strabismus with subsequent contact correction and treatment is considered to be necessary for medical and labour rehabilitation of such patients. PMID- 2255485 TI - [The function of the posterior corneal epithelium after exposure to ultraviolet laser radiation]. AB - The method of contact mirror microscopy was used for assessment of the state of posterior epithelium of rabbit corneas before and after the action of laser ultraviolet radiation, lambda = 0.337 mmc. It was found that the usage of energy density of 5-20 mwt/cm2 and time exposures [correction of expositions] of 1, 5, 10, 15 min. in the terms of follow-up from 1 hour to 3 months is harmless for cells of posterior epithelium of the cornea in experiment. The method of mirror microscopy widens criteria of in vivo objective assessment of coherent radiation action on the cornea, that is important for deciding the questions about security and optimization of energetic parameters of laser therapeutic actions. PMID- 2255486 TI - [The stimulating effect of helium-neon laser radiation on rabbit eyes]. AB - Local and general reactions have been studied after subjecting a rabbit eye to dispersed helium-neon laser radiation, 8 x 10(-6) wt/cm-2, 10 min daily for 10 days. There were recorded increase of blood filling of the uveal tract of the eye, changes in the indices of systemic hemodynamics, systolic and diastolic pressure, stroke and minute volume of blood volume, activation of separate links of antioxidant system connected both with oxidation-reduction of thiol disulfide system and the functioning of antiperoxide enzymes. The activation of antioxidant system has a local character, the changes in the retina of the eye and pigmented epithelium is expressed stronger than in the peripheral blood. The results obtained speak about relationship between the stimulating effect of helium-neon laser radiation on the rabbit eye and activation of antioxidant system. PMID- 2255487 TI - [Current trends in the hemodynamic study of the eye with glaucoma]. PMID- 2255488 TI - [Errors in the diagnosis of tuberculosis of the eyes]. PMID- 2255489 TI - [A comparative evaluation of the efficiency of treating viral keratitis with fibronectin]. PMID- 2255490 TI - [Combined arteriovenous malformations of the brain and membranes of the ocular fundus]. PMID- 2255491 TI - [A case of uveitis in all the children of one family]. PMID- 2255492 TI - [The clinical characteristics and treatment tactics of vertical strabismus]. AB - Examination of 328 patients with vertical squint has revealed peculiarities of its clinical forms. Their characteristics are: I. Concomitant vertical squint; II. A mixed form--concomitant convergent or divergent squint with a vertical component; III. Paretic or paralytic vertical squint; IV. Atypical kinds of vertical squint. Special attention is drawn to the presence of torticollis, difference in lid slit width, pseudoptosis, diplopia. Basic principles of treatment of vertical squint corresponding the clinical form are suggested. Results of treatment in patients with different forms of vertical squint are analysed. PMID- 2255493 TI - [The results of simulating congenital pathology of the extraocular muscles]. AB - The paper describes results after calculating the distribution of tensions in the cornea in case of anomalies in the action and insertion of oculomotor muscles. The calculation was made on the basis of theories of thin coats considering the gradient of corneal thickness. By the results of the calculation, the lines of equal tensions (isochroms) were built, the forms of which is well correlated with clinical results. The calculation has shown that the rounding of one of the angles of interference rhombus and its displacement towards the centre of the picture speak about either a functional deficiency of a muscle inserted into the eye ball in this place or about displacement of the point of its insertion from the limbus along the meridian of its action; displacement of one the angles of interference rhombus from the meridian speaks about displacement of the point of efforts exertion of the corresponding muscle into the same direction. The calculation made confirms correctness of our knowledge about the nature and properties of interference pictures observed on the cornea in a polarised light. PMID- 2255494 TI - [The use of an optical polarization method for the evaluation of oculomotor muscle function in vertical deviation]. AB - The state of oculomotor muscles in vertical deviation has been studied by means of polarioptic method. A control group included 62 healthy persons, of them 24 (48 eyes) with orthophoria, 19 (38 eyes) with esophoria and 19 (38 eyes) with exophoria. A group of patients with vertical deviation included 39 (78 eyes) with concomitant convergent squint with a vertical component and 9 children (18 eyes) with concomitant vertical squint without a horizontal component. In patients with vertical squint, the polarioptic method revealed high frequency of functional muscular imbalance and anatomic asymmetry of muscles of both horizontal and vertical action. It is shown that in case of convergent squint with a vertical action, not only the frequency is higher, but to a much greater degree increases the value of anatomic asymmetry in the position of horizontal muscles. PMID- 2255495 TI - [The "3-step" test in the diagnosis of vertical strabismus]. AB - Examination of the oculomotor apparatus in 130 patients after scleroplastic operations and in 65 patients with vertical squint, forced position of the head, by means of the method of coordimetry and a proposed Parks' (in Hardesty's modification) test "three steps" has shown this test to be valuable as a simple, requiring no technical equipment and accessible to practitioners, method of diagnosing vertical squint in children and adults. It is shown that this test can be computerized and assessed by means of microcalculators. PMID- 2255496 TI - [The syndrome of congenital unilateral hyperfunction of the inferior oblique muscle: clinico-pathogenetic variants]. AB - Examination of 21 children with unilateral congenital paresis of superior oblique muscle and of 50 children with unilateral hyperfunction of inferior oblique muscle has shown that both forms of early squint have a picture of the same syndrome of oblique muscles disfunction as a primary congenital defect of muscular balance. A constant sign of the syndrome is unilateral hypertropia of adduction, disappearing or sharply reducing in abduction of the upward deviated eye, as well as horizontal squint of a convergent type, more frequently esotropia, nonaccommodative or partially accommodative, accompanied by a V-sign. It is proposed to name this syndrome as "syndrome of congenital unilateral hyperfunction of inferior oblique muscle". PMID- 2255497 TI - [The diagnosis and surgical treatment of congenital convergent strabismus with a vertical component]. AB - Examination of eyes in a polarized light in 108 children and 24 adults with congenital concomitant convergent squint with a vertical component has shown displacement of internal angles of the rhombus of interference pictures from the horizontal axis, this speaking about anomaly of internal rectus muscles insertion. The patients with congenital squint were treated by two methods proposed by the author--recession of internal rectus muscles, and in case of residual deviation--partial resection of external rectus muscles. Symmetrical position was achieved in 107 children and 21 adults; stable binocular vision could be developed only in children (25.2%). PMID- 2255498 TI - [The surgical treatment of vertical strabismus in children]. AB - The paper deals with principles of surgical treatment of vertical squint caused by paresis of muscles of vertical action. The authors consider to be optimal one stage surgical intervention consisting of enhancing the paretic muscle and weakening the antagonist of the same eye, i. e. the rectus and oblique muscles. The dosage of the surgery was calculated considering the angle of squint. A new method is proposed for calculating the position, on the sclera, of the point of fixation of inferior oblique muscle at its recession. Results of 73 operations are analysed. Orthotropia was achieved in 72.6% of patients. The authors recommend the operation to be widely used in clinical practice. PMID- 2255500 TI - [Vertical strabismus and methods for its treatment]. AB - The paper analyses results after treatment of 80 children with vertical squint, of them 8 patients had vertical squint alone and the rest--association of vertical and horizontal squint. Most of the children had divergent vertical deviation. For correction of vertical squint, myoplastic operations were used. In case of mixed squint with the angle of 5-7 degrees, the lengthening of horizontal muscles was made at the first stage. In case of more pronounced angles of vertical deviation, one-stage lengthening of horizontal and vertical rectus muscles was made. In case of vertical squint alone, superior and inferior rectus muscles were operated. The positive effect was achieved in 80% of cases. PMID- 2255499 TI - [The clinical picture and treatment of dissociated vertical strabismus]. AB - The paper describes clinical picture of a special form of oculomotor pathology- dissociated vertical squint characterized by vertical deviation into different directions, a different value of vertical deviation in abduction-adduction, a forced position of the head, infrequently--pseudoptosis of the upper lid of the downwards deviated eye, normal or slightly reduced visual acuity. The approach of surgical treatment is described. A stage-by-stage surgical treatment in 125 patients resulted into elimination of deviation in 67.2% of cases, restoration of normal binocular vision at different distances in 23.2%, binocular vision for near in 11.2% of patients. Orthoptic-diploptic treatment is shown to be expedient in patients with periodically small (to 8 degrees) angles of dissociated vertical squint, leading to restoration of binocular vision in 54.4% of patients. PMID- 2255501 TI - [Treatment of vertical strabismus using binarimetry]. AB - The paper analyses results after treatment of patients with vertical squint (53 persons) using a principally new method--binarimetry, as one of diploptic methods. All patients had residual vertical deviation after surgical treatment or a small angle (to 10 degrees). The device and the method of treatment are described. In the most of patients, binocular vision was restored (77.3%) on account of development of vertical fusional reserves and correction of residual deviation. PMID- 2255502 TI - [The physical and clinical eye refraction of preschoolers and young schoolchildren]. AB - Physical and clinical eye refraction was studied in 608 children aged from 3 to 12 years. The formation of refraction of the eye at the time of its growth is based on correlative connexions between anatomo-optic parameters and between refractive media themselves. Spherical and astigmatic refraction are determined by refractive media having, in their most part, astigmatism. In the period of the growth of the eye, its physical and clinical refraction changes. To prevent a fall of visual functions and disturbances in the musculo-accommodative system of the eye, early optic correction of ametropia is recommended and, if indicated, pleoptic-orthoptic treatment. PMID- 2255503 TI - [Role of heredity in myopia]. AB - Analysis of genealogic data of 100 patients addressed on occasion of myopia in 1987-1988 has shown that in 85% of the subjects myopia was of a clearly hereditary character (in 35%--a dominant and in 50%--a recessive hereditary). The author compares his own results with literature data and draws attention to Steiger's views about formation of myopic refraction and the role of hereditary factor in this process. In the light of the mentioned data, the author considers it expedient to work out a programme of special researches for development of a method of prognosticating initial myopia and a correction of several ways for approbation of existing methods of prevention of progressive myopia. PMID- 2255504 TI - [Thermography in the diagnosis of vascular neuritis of the optic nerve]. AB - A new method for diagnosing vascular neuritis of optic nerve by means of thermography is proposed. Among 47 patients with diagnosis of optic nerve neuritis of unclear etiology, in 37 of them vascular genesis of the disease was diagnosed. The thermograms have shown appearance of dark "cold" spots and a fall of temperature by 1.0 degrees C and lower in the supraorbital and orbital areas of the affected eye. The method is highly precise (90.27%, sensitive (94.9%) and doesn't require long time. PMID- 2255506 TI - [Role of photoreactivation in case of corneal damage from ultraviolet radiation]. AB - Experimentally, the role of photoreactivation in appearance of ultraviolet lesions of corneal epithelium has been studied in white rats. The lesions were induced by ultraviolet radiation, 0.28 mcm wavelength, and intensive (20000 lx) light of a xenon lamp with light filters was used as a reactivating light. The damaging dose as a reactivating light. The damaging dose of ultraviolet radiation by photokeratitis criterion was 11 +/- 2.4 mJ.cm-2. Simultaneous illumination of the animal eye by the damaging ultraviolet light and reactivating radiation exceeded a damaging threshold to 18 +/- 4.0 mJ.cm-2. The results obtained have convincingly shown, that photoreactivation, as a phenomenon, manifested itself in the corneal epithelium and was detected by biomicroscopy of the eye with epithelium staining by a 1% fluorescein solution. PMID- 2255505 TI - [One-stage extracapsular cataract extraction with sinusotrabeculotomy in patients with combined glaucoma and cataract]. AB - The paper deals with the question about surgical treatment of patients with glaucoma associated with cataract. A new technique of one-stage extracapsular cataract extraction with sinusotrabeculotomy is proposed. Its main point is a change in the sequence of stages: stage I--opening of anterior lens capsule, stage II--antiglaucomatous operation, stage III--extraction of lenticular nucleus and masses through a corneal incision. The operation was made in 30 patients (31 ages). The follow-up period was 2 years. Normalization of intraocular pressure was achieved in all patients, in one eye--miotics had to be used. All patients showed a rise of visual functions: in 21 of 31 eyes vision rose to 0.3 and higher. In one patient vision fell after a year because of progression of the glaucomatous process in the presence of normal intraocular pressure. One-stage extracapsular cataract extraction with sinusotrabeculotomy can be made at any stage of glaucoma. By the authors' data, contraindications can be a rise of intraocular pressure above 40.0 mm Hg as well as the presence of a single eye and severe course of hypertonic disease. PMID- 2255508 TI - [Current status and methods to improve the efficiency and quality of prophylactic examinations of patients with sequelae of eye injuries in the Ukrainian SSR]. PMID- 2255507 TI - [The efficiency of treating ulcerative corneal lesions with fibro nectin]. AB - The paper analyses results after experimental studies of effectiveness of medical forms of fibronectin used in a form of eye drops for treatment of infectious keratitis on a model of bacterial corneal ulcer in 30 rabbits (60 eyes). The results obtained speak about a pronounced stimulating action of fibronectin on reparative processes: almost a twice quicker epithelialization of corneal defects (by 46.8%) and a quicker reverse development of inflammatory signs as compared with the control group of animals. Results of experimental studies allow to recommend fibronectin for treatment of patients with infectious keratitis, bacterial ulcers of the cornea. PMID- 2255509 TI - Features of Sorsby's fundus dystrophy. PMID- 2255510 TI - Variations on pigtail probe technique. PMID- 2255511 TI - Practice implications of the Glaucoma Laser Trial. PMID- 2255512 TI - The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group. AB - The Glaucoma Laser Trial, a multicenter, randomized clinical trial involving 271 patients, was designed to assess the efficacy and safety of argon laser trabeculoplasty (ALT) as an alternative treatment with topical medication for controlling intraocular pressure (IOP) in patients with newly diagnosed, previously, untreated primary open-angle glaucoma (POAG). Each patient had one eye randomly assigned to ALT (the laser first [LF] eye) and the other eye assigned to timolol maleate 0.5% (the medication first [MF] eye). Medication was initiated or changed for either eye according to the same stepped regimen if the IOP was not controlled. Throughout the 2-year follow-up, LF eyes had lower mean IOPs than MF eyes (1-2 mmHg), and fewer LF eyes than MF eyes required simultaneous prescription of two or more medications to control IOP (P less than 0.001). After 2 years of follow-up, 44% of LF eyes were controlled by ALT, 70% were controlled by ALT or ALT and timolol, and 89% were controlled within the stepped medication regimen. After 2 years, 30% of MF eyes remained controlled by timolol, and 66% were controlled within the stepped regimen. There were no major differences between the two treatment approaches with respect to changes in visual acuity or visual field over the 2 years of follow-up. PMID- 2255513 TI - The use of Molteno implant and anterior chamber tube shunt to encircling band for the treatment of glaucoma in keratoplasty patients. AB - This retrospective study reviews the results of 35 keratoplasty patients with complex corneal and glaucoma disease, who received Molteno-type (n = 25) or anterior chamber tube shunt to encircling band (ACTSEB)-type (n = 10) implant for the treatment of difficult glaucomas. The implant was placed before the keratoplasty in 14 eyes, during the keratoplasty procedure in 6 eyes, and subsequent to the corneal surgery in 15 eyes. Mean follow-up for the keratoplasty was 25.46 months (range, 6-58 months) and 24.74 months (range, 7-42 months) for the seton procedure. Graft rejection occurred in 12 (34%) of 35 eyes and was progressive in 9 eyes. Nonimmunologic failure was seen in 9 (26%) of 35 eyes. Grafts were repeated in ten eyes with eight of these (80%) remaining clear at a mean of 14.4 months. Considering the results of the repeat grafts, 25 (71%) of 35 eyes achieved clear transplants. Overall, 46% of patients had final visual acuities of 20/100 or better and 69% had final visual acuities of 20/400 or better. The mean preoperative intraocular pressure (IOP) of 34.54 mmHg (range, 14 68 mmHg; standard deviation [SD], 11.51) was lowered to a mean of 14.65 mmHg (range, 6-30 mmHg; SD, 4.49). In the final analysis, 30 (86%) of 35 eyes were judged successful from a glaucoma standpoint. We conclude that the Molteno- and ACTSEB-type implants are viable treatment alternatives in this difficult glaucoma group. PMID- 2255514 TI - Effects of topical glaucoma drugs on fistulized rabbit conjunctiva. AB - Conjunctival fibroblastic proliferation with contracting scar formation has been implicated as a possible cause of glaucoma filtering surgery failure. The effects of glaucoma medications on bulbar conjunctiva were evaluated in both eyes of 20 pigmented rabbits, with 5 rabbits per group each receiving singular topically applied daily doses of either 0.5% timolol, 1% epinephrine, 4% pilocarpine, or artificial tears in a masked fashion for 4 months. Posterior lip sclerectomies were performed in 16 rabbits--4 from each treatment group. The remaining four rabbits served as nonsurgical controls. Four additional rabbits, which had not received eye drops, were included as a nonmedicated control group, with one rabbit serving as a nonsurgical control. Immunostaining was performed to identify the presence of myofibroblasts in fistulized conjunctiva. Treated surgical eyes, regardless of medication, had higher myofibroblastic cell proliferation than treated nonsurgical eyes. Among fistulized eyes, all medications increased cell proliferation, with pilocarpine eliciting the most dramatic increase compared with all other groups. PMID- 2255515 TI - Assessment of cataracts from photographs in the Beaver Dam Eye Study. AB - Presence and severity of age-related cataract was determined in adults 43 to 84 years of age in Beaver Dam, Wisconsin. Duplicate photograph gradings for nuclear sclerosis (n = 1160), cortical opacities (n = 1159), and posterior subcapsular cataract (n = 1137) were performed. There are five levels of nuclear sclerosis. Exact agreement occurred in 64.7% of the cases; agreement within one category in 99.8%. For cortical opacities, graders estimate involved area in nine segments of the lens. When the continuous scale is divided into 12 categories of severity, exact agreement varied between 73.5 and 82.4%; for agreement within one category, rates varied between 84.6 and 89.9%. For posterior subcapsular cataracts, exact agreement for involvement of the central circle occurred in 95.0% and agreement within one category occurred in 97.7%. Intraobserver comparisons disclosed similar concordance. These grading schemes are semiquantitative, reproducible, and can be performed for the large numbers of photographs from population-based studies. PMID- 2255516 TI - Botulinum treatment of childhood strabismus. AB - Four hundred thirteen children ranging in age from 2 months to 12 years were treated for strabismus by botulinum injection of extraocular muscles. An average of 1.7 injections per patient was given. Follow-up at an average of 26 months after the last injection (minimum, 6 months) was available on 362 children (88%). The frequency of correction of 10 prism diopters (PD) or less in various groups of strabismus cases was: all 362 cases, 61%; all esotropia, 66%; infantile esotropia, 65%; and exotropia, 45%. Smaller deviations (10-20 PD) were more frequently corrected (73%) than were larger deviations (20-110 PD, 54%). The frequency of correction to 10 PD or less of previously operated cases was not different from that of unoperated cases. There was no globe perforation, amblyopia, or visual loss produced by the injection treatment in this series. PMID- 2255517 TI - Prolonged recoverability of desiccated adenovirus type 19 from various surfaces. AB - Epidemic keratoconjunctivitis is a highly contagious disease whose transmission has been linked to the ophthalmologist's office. The authors studied the ability of adenovirus 19 (ADV 19) to survive on surfaces commonly found in the office setting. An initial in vitro laboratory experiment demonstrated that ADV 19 in a desiccated state could be recovered up to 8 days from paper, and up to 10 days from cloth, metal, and plastic. The amount of recovered ADV 19 was significantly greater (analysis of variance, P less than 0.0001) from nonporous surfaces (plastic, metal) compared with porous surfaces (cloth, paper). A second experiment demonstrated that 35 days was the maximum length of time that desiccated ADV 19 could be recovered from a nonporous surface (plastic). The authors conclude that despite drying, ADV 19 is a hearty virus that remains potentially infectious for a long time on various surfaces that may be found in an ophthalmologist's office. PMID- 2255519 TI - Intraocular lens implantation after penetrating keratoplasty. Improved unaided visual acuity, astigmatism, and safety in patients with combined corneal disease and cataract. AB - Twenty-two eyes with combined corneal disease and cataract were followed prospectively after nonsimultaneous intraocular lens (IOL) placement after penetrating keratoplasty; the majority had a penetrating keratoplasty and planned extracapsular cataract extraction (ECCE) followed later by the placement of an IOL. The mean follow-up after IOL placement was 25 months (range, 3-55 months). No graft failures occurred after secondary surgery. All graft sutures were removed in 86% (19/22) of eyes before IOL surgery. Ninety-five percent (21/22) of the eyes achieved refractive errors within 2 diopters (D) of the desired result. Corneal astigmatism decreased from 4.88 to 2.92 D after secondary surgery and wound revision. Unaided visual acuity was 20/40 or better in 68% (15/22) and 20/100 or better in 91% (20/22) of the eyes. The advantages of excellent unaided visual acuity, reduced astigmatism, and lack of anisometropia and graft failure outweigh the disadvantage of some delay in final visual rehabilitation (11 months) and increased secondary capsulotomy rate (85%) in this series with two separate surgeries compared with previously reported triple procedure results. PMID- 2255518 TI - Posterior infectious crystalline keratopathy with Staphylococcus epidermidis. AB - Two cases of infectious crystalline keratopathy located in the posterior stroma after penetrating keratoplasty are presented. Topical steroids and suture removal were risk factors in both cases. In the first case, a moderate anterior chamber reaction was present. Crystalline infiltrates persisted on topical and systemic steroid therapy. In the second case, deep corneal ulceration, hypopyon, and vitreitis were noted. A vitreous aspirate showed rare gram-positive cocci in pairs. The corneal ulceration and crystalline keratopathy persisted despite intravitreal and topical antibiotics. Therapeutic penetrating keratoplasty was performed in both cases. Staphylococcus epidermidis sensitive to vancomycin was isolated from corneal tissue. Light microscopy documented aggregates of gram positive bacteria anterior to Descemet's membrane, with an overlying keratitis. Electron microscopy in the second case showed all bacteria within stromal keratocytes. No clinical recurrence was seen using topical vancomycin. As demonstrated in the cases presented, infectious crystalline keratopathy can occur exclusively in the deeper layers of the cornea. Isolation of S. epidermidis, associated inflammation, and intraocular spread of organisms are rare findings. PMID- 2255520 TI - Rhabdomyosarcoma of the ciliary body. AB - Rhabdomyosarcoma is the most common malignant orbital tumor of childhood. It has twice been reported to arise within the globe from the iris. In addition, teratoid medulloepithelioma, a tumor arising from the ciliary epithelium, can contain a rhabdomyoblastic component, often in combination with other heteroplastic elements. The authors report what may be the first recorded case of an embryonal rhabdomyosarcoma of the ciliary body, possibly representing a one sided differentiation of a malignant teratoid medulloepithelioma. PMID- 2255521 TI - Bicarbonate-buffered lidocaine-epinephrine-hyaluronidase for eyelid anesthesia. AB - A double-masked, randomized clinical trial was conducted to determine if subcutaneous eyelid injections of a bicarbonate-buffered lidocaine-epinephrine hyaluronidase mixture were less painful than unbuffered injections. Twenty-one patients received both buffered (pH = 7.4) and unbuffered (pH = 4.6) injections. After each injection, patients recorded pain on a scale of 0, "no pain," to 10, "severe pain." Mean pain score for buffered injections was 2.0 versus 4.1 for unbuffered injections (P = 0.0003). Seventeen (81%) of 21 patients ranked the buffered injection less painful. Use of a bicarbonate-buffered lidocaine epinephrine-hyaluronidase mixture is effective in making ophthalmic anesthesia less painful. PMID- 2255522 TI - Results of blepharoptosis surgery with early postoperative adjustment. AB - The authors reviewed 157 cases (207 eyes) of blepharoptosis corrected by external levator resection. Twenty-eight patients (29 eyelids) had unsatisfactory results. The authors adjusted 13 eyelids within 1 week of surgery. Eleven eyelids were reoperated 6 or more weeks after surgery. The mean delay between the initial and final surgery in the early group was 2.0 weeks; and, for the late group, 33.5 weeks. For those having reoperations, there was no difference in the number of procedures required to achieve satisfactory outcomes. Four patients (5 eyelids) with unsatisfactory results were offered, but declined, late repair. Early or late reoperation is effective in correcting unsatisfactory results after external levator resection. The benefits of early surgery are a reduction in time to final result, the ease with which it is performed, potential cost savings, and the opportunity one has to correct unsatisfactory results. PMID- 2255523 TI - Orbital complications secondary to endoscopic sinus surgery. AB - Eight cases of significant orbital complications associated with endoscopic sinus surgery are described. The anatomic problems generally fall into four categories: nasolacrimal sac or duct injury, extraocular muscle injury, intraorbital hemorrhage/emphysema, or optic nerve injury. The successful management of each complication depends on a thorough knowledge of the anatomy and pathophysiology of the orbital injury. Return to normal function of the traumatized orbital structures after medical and/or surgical intervention is anticipated. However, direct optic nerve injury with immediate visual field and/or acuity deficit is usually irreversible. PMID- 2255524 TI - Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the literature. AB - Thirteen patients with dilated intraorbital optic nerve sheaths with an expanded, patulous cerebrospinal fluid (CSF) space were studied with high-resolution computed tomography (CT) or magnetic resonance imaging (MRI). Eleven patients had bilateral findings. Headache or visual complaints, or both, were present in all patients. Signs of optic nerve dysfunction were present in eight patients. Three patients had visual acuity worse than 20/200. Cerebrospinal fluid pressure was mildly elevated in two patients. Three patients underwent a surgical procedure; visual acuity improved in one. The authors propose the term meningocele for this condition and suggest MRI with fat-suppression techniques and off-axis sagittal views as the radiographic procedure of choice. PMID- 2255525 TI - Retained intraocular foreign bodies and endophthalmitis. AB - Retained intraocular foreign bodies (IOFBs) are associated with endophthalmitis in approximately 7 to 13% of cases. The role of prompt surgical removal of the foreign body along with the use of intravitreal antibiotics in reducing this figure is uncertain. Retained IOFBs presenting to The Medical College of Wisconsin between July 1986 and June 1989 were reviewed. A total of 27 cases were evaluated and surgically treated. None of the 27 cases presented with or developed clinical signs of endophthalmitis, yet bacterial cultures of the removed intraocular material were positive in seven cases (foreign body in 5 cases, the aqueous fluid and the vitreous fluid in 1 case each). All eyes presenting within 24 hours of injury underwent immediate surgery (average, 4.5 hours after presentation). Of the seven eyes with positive intraocular cultures, all had pars plana vitrectomy removal of the IOFB and three of these eyes received intravitreal antibiotics at the time of surgery over concern of a high risk of infection. Two of these eyes eventually grew out the Bacillus sp. All eyes received subconjunctival antibiotics and postoperative topical and systemic antibiotics. Even after the positive cultures, no signs of clinical infection developed in any of the eyes. All seven eyes retained excellent visual acuity of 20/70 or better at an average of 10 months' follow-up. Follow-up ranged from 1 to 31 months. Prompt surgical intervention, the use of intravitreal antibiotics in high-risk-type injuries, and the possible use of vitrectomy surgery may reduce the incidence and severity of endophthalmitis. PMID- 2255526 TI - Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula. AB - Serous detachment of the macula is a well-known complication in patients with an optic nerve pit. Despite the many descriptions of this condition and possible treatment options, the long-term natural history is not well known. The authors identified 15 eyes of 15 consecutive patients seen over 21 years who were diagnosed with a serous detachment of the macula arising from an optic nerve pit. Average length of follow-up was 9 years. Twelve eyes lost three or more lines of vision, two eyes remained unchanged, and only one eye improved. All of the 12 eyes losing three or more lines of vision experienced this decrease within the first 6 months of follow-up. Although only two patients had a visual acuity of 20/200 or less initially, 12 of 15 patients had a visual acuity of 20/200 or less at the time of their last examination. The appearance of the macula at last examination included cystic changes of the neurosensory retina, full-thickness hole formation, retinal pigment epithelial mottling, and lamellar hole formation in the outer retinal layer. The long-term visual prognosis in patients with optic nerve pit and untreated serous retinal detachment of the macula is poor, and visual loss occurs within 6 months of the serous detachment. PMID- 2255527 TI - The risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion. AB - In this cross-sectional study, the authors evaluated 197 patients diagnosed with central retinal vein occlusion (CRVO) at the Wilmer Ophthalmological Institute between 1980 and 1985 to determine the risk of systemic disease and mortality. Complete follow-up information for mortality was obtained in 191 (97%). National Health Interview Survey (NHIS) patients and Wilmer cataract patients formed two comparison groups. The prevalence of hypertension was significantly elevated in the CRVO cases when compared with both comparison groups (P less than 0.03, 0.005). The prevalence of diabetes mellitus was increased in CRVO cases in comparison with the NHIS group (P less than 0.005). The prevalence of cerebrovascular or cardiovascular disease was the same for all three groups, as was overall mortality. Mortality was not increased in CRVO cases as compared with United States mortality rates. PMID- 2255528 TI - Visual prognosis correlated with the presence of internal-limiting membrane in histopathologic specimens obtained from epiretinal membrane surgery. AB - Forty-one patients with a unilateral, macular epiretinal membrane (ERM) underwent pars plana vitrectomy and membrane peeling to improve the visual acuity. The authors retrospectively reviewed the histopathology of the vitrectomy specimen in each instance to determine whether the presence of internal-limiting membrane (ILM) had an adverse effect on visual acuity. Eleven specimens contained long segment of ILM, as determined by light microscopy. With a minimum of 6 months of follow-up, none of these 11 eyes achieved a visual acuity of better than 20/60. Of 30 eyes that did not have ILM present, 41% achieved a visual acuity of 20/60 or better. Overall, 29% of the eyes in the entire series achieved 20/60 or better visual acuity. The difference between the group with ILM versus that without ILM was statistically significant (P = 0.01). The presence of long segments of ILM within the histopathologic specimen after vitreous surgery for removal of a macular ERM appears to indicate a less favorable visual outcome. PMID- 2255530 TI - The repair of rhegmatogenous retinal detachments. American Academy of Ophthalmology. AB - Current techniques of rhegmatogenous retinal detachment repair allow most retinal detachments to be repaired successfully. The success of repair depends on a careful preoperative examination and choice of an appropriate surgical procedure. The surgical procedure must be tailored to the individual eye based on a detailed preoperative examination of the retina and vitreous. Postoperative complications are not infrequent compared to many other ophthalmic surgical procedures such as cataract extraction and strabismus repair. The surgeon must observe the eye carefully in the postoperative period to monitor and treat any complications as they arise. Improvements in surgical techniques coupled with a better understanding of the pathophysiology of rhegmatogenous retinal detachment continue to improve the anatomic and functional success of retinal detachment repair. PMID- 2255531 TI - Hemiglossectomy by laser. Evaluation of articulation deficits. PMID- 2255529 TI - Semiconductor diode laser photocoagulation in retinal vascular disease. AB - The authors successfully performed clinical transpupillary retinal photocoagulation in 30 eyes of 26 patients with retinal vascular disease using a gallium-aluminium-arsenide (GaAlAs) diode laser emitting at 805 nm. Retinal photocoagulation was performed at treatment powers of 300 to 1300 mW and exposure durations of 0.2 to 0.5 seconds with a 200-microns diameter treatment spot. Patients treated with both diode and argon green lasers required 4.5 +/- 1.8 times greater mean laser energy with diode compared with argon to create ophthalmoscopically similar lesions. Parallel experimental retinal photocoagulation in Chinchilla rabbits required 3.1 +/- 0.9 times more power to create ophthalmoscopically similar lesions with the diode laser than with the argon laser. Intraoperative subretinal hemorrhage occurred rarely in patients with an incidence of 4 (0.44%) of 9021 treatment spots. Patients complained of moderate-to-marked pain in 10 (43%) of 23 treatments initiated under topical anesthesia. A transpupillary diode laser may be used clinically to perform therapeutic retinal photocoagulation. PMID- 2255532 TI - Magnetic resonance imaging in head and neck oncology. PMID- 2255533 TI - [Preoperative diagnosis in patients with malignant tumors of the head and neck regions]. PMID- 2255534 TI - [Thoughts regarding the TNM classification of laryngeal tumors]. PMID- 2255535 TI - [Epidermal cysts of the temporal bone pyramid. Report on 20 cases]. PMID- 2255536 TI - [Ultrasonic diagnosis of parotid diseases (B-image)]. PMID- 2255537 TI - [Functional results of radical neck dissection]. PMID- 2255538 TI - Endolaryngeal microsurgery in vocal cord carcinomas. Indications and results. PMID- 2255539 TI - [Metastases of laryngeal cancer and their effect on 5-year survival]. PMID- 2255540 TI - [Studies of occupational factors in ORL neoplasms based on the data of the ORL Clinic of the State Polyclinic in Berlin-Buch]. PMID- 2255541 TI - [Photodynamic therapy of tumors. Principles and the first results of the experiments]. PMID- 2255542 TI - [Incidence and prognosis for malignant head and neck neoplasms in the Democratic Republic of Germany. Comparisons for the years 1961/1964 and 1981/1984]. PMID- 2255543 TI - [Speech rehabilitation after laryngectomy by voice prosthesis. Principles, results and problems]. PMID- 2255544 TI - Therapeutic problems of aged patients with malignant tumors of the head and neck. PMID- 2255545 TI - Plastic reconstruction of oral cavity and pharynx with microsurgically revascularized intestinal grafts. PMID- 2255546 TI - [Self-help groups of patients with ORL neoplasms]. PMID- 2255547 TI - Treatment and results of maxillary sinus carcinoma. PMID- 2255548 TI - [Reconstruction of the pharynx using a revascularized jejunum transplant]. PMID- 2255549 TI - The problem of second malignant primary neoplasm development in ENT oncology. PMID- 2255550 TI - The role of functional neck dissection in ENT oncology. PMID- 2255551 TI - The patterns of cancer care studies in otolaryngology. PMID- 2255552 TI - The experience with parotid gland surgery at the Department of Otolaryngology of the University of Tubingen over an 18 years period. PMID- 2255553 TI - [Principles of the treatment of malignant tumors of the oropharynx in the ORL Disease Clinic in Erlangen]. PMID- 2255554 TI - A monoclonal immunotoxin against laryngeal carcinoma cells. PMID- 2255555 TI - [Cancer of the larynx in patients under 40 years of age]. AB - 440 patients with the plano-epithelial laryngeal cancer were radically treated by radiotherapy in Oncologic Department ZOZ in Lublin during the years 1976-1985. Among them were 23 (5.2%) "young" patients, aged below 40. In this group 10 patients (43%) revealed the first grade of clinical stage of the disease, whereas in remaining material there were 25% of cases in the first grade. The therapeutic effects in "young" group were the same as in the rest of cases. The percentage of "young" cancer patients became greater during the time: in 1976-80-4.1%, in 1981 85-6.1%. PMID- 2255556 TI - [Causes of delayed treatment of patients with cancer of the larynx and hypopharynx in the north-eastern region of Poland]. AB - Early diagnosis and treatment of the larynx and hypopharynx cancer is crucial in connection of the therapeutic effects and prognosis. However, our experiences pointed out that the patients came too late for treatment, sometimes several months after the beginning of symptoms. They always revealed at this moment of the first consultations more advanced local lesions and metastases in the neighbouring regions. We analysed the material of 184 patients treated in ENT Clinic of Medical Academy in Bialystok according to the delayed reporting to treatment. The reasons of the delayed reporting were also evaluated. The misdiagnosis was not the main reason of the delayed treatment. PMID- 2255557 TI - [Changes in hydroxyproline levels in the blood and urine of patients with laryngeal cancer after radiotherapy]. PMID- 2255558 TI - The primary antibody response of malaria patients to Plasmodium falciparum sexual stage antigens which are potential transmission blocking vaccine candidates. AB - Thirty serum samples collected from adult patients attending the Hospital for Tropical Diseases, London, with P. falciparum malaria, were studied. Sera were screened by indirect immunofluorescence for anti-gametocyte antibodies. Twelve of the serum samples taken from 14 patients with primary infections were found to have both IgM and IgG antibodies to gametocyte antigens and total Ig titres comparable with those of patients who had had previous malaria attacks. Sera of individuals from hyperendemic areas have been found to immunoprecipitate the 230 and 48/45 kD gametocyte surface antigens which are known targets of transmission blocking antibodies. To investigate the epitope specificity of the serum samples from our adult patients, competitive ELISAs with 3 monoclonal antibodies (MAbs) that block transmission and recognize different epitopes on the 48/45 Kd antigen, were carried out. Specific antibodies for these epitopes were found in 60% of the sera while nearly a third were able to inhibit the binding of at least two MAbs. PMID- 2255559 TI - An antigen specific to the liver stage of rodent malaria recognized by a monoclonal antibody. AB - Vaccines currently being evaluated against malaria are based on proteins derived from the blood, sporozoite and sexual stages. Antigens from the liver stage, which is now recognized as the major target of protective sporozoite induced immunity, have received comparatively little attention. This paper describes the generation of a monoclonal antibody (MoAb), which recognizes an antigen specific to the liver stage of the rodent malaria Plasmodium berghei. The antigen is expressed throughout liver stage development and appears to be localized to the parasitophorous vacuole membrane. The MoAb did not affect the growth of liver stages cultured in vitro nor could protection be demonstrated in vivo following passive transfer of the antibody. PMID- 2255560 TI - Production of tumour necrosis factor during murine cutaneous leishmaniasis. AB - We have assessed the role of tumour necrosis factor-alpha (TNF) during cutaneous leishmaniasis and demonstrated that significant levels of TNF were released by spleen cells from infected mice after in vitro restimulation with Leishmania major promastigotes. Spleen cells from both genetically resistant and genetically susceptible mice were equally capable of producing TNF. After challenge with bacterial endotoxin, TNF activity could also be demonstrated in the serum of L. major-infected mice and the titres correlated with the course of cutaneous disease in susceptible and resistant mice. TNF did not exert a direct leishmanicidal effect in vitro. Furthermore, our study indicated that macrophages are the source of L. major-induced TNF activity and that its elicitation is dependent on the presence of T cells. These findings suggest that TNF acts in concert with other cytokines produced during L. major infection and that its role depends on the composition of T cell subsets and cytokines present. PMID- 2255561 TI - Serum antibody specificities to Leishmania aethiopica antigens in patients with localized and diffuse cutaneous leishmaniasis. AB - In order to characterize the antigenic determinants of Leishmania aethiopica, we have analysed by immunoblotting the antibody reactivity of leishmaniasis patients with either the localized (LCL) or diffuse (DCL) clinical forms of disease. In this study we have compared the reactivity of antibodies from eight LCL and DCL patients to parasites isolated from each individual, or the parasite isolates of the other LCL and DCL patients studied. The immunoblot profiles of antibodies from LCL patients differed from the antibody profiles of DCL patients. Serum antibodies from LCL patients showed limited recognition of somatic antigens of less than Mr 50,000 which were recognized by antibodies present in DCL patients. A direct comparison of individual LCL and DCL patient derived promastigotes determined that the lack of antibody to these antigens in LCL patients was not due to the differential expression of these determinants by the LCL and DCL derived promastigotes. The results of this study suggest that although either LCL or DCL derived promastigotes express a wide variety of antigenic moieties which are potentially reactive with antibodies, only a subset of antibodies against these specificities develop in any individual patient, during active infection. PMID- 2255562 TI - MHC-restricted antibody responses to Trichuris muris excretory/secretory (E/S) antigen. AB - Two panels of H-2 recombinant mice were used in a detailed serological study to analyse the role of H-2-linked genes in the control of the antibody response to excretory/secretory (E/S) antigens of Trichuris muris. An apparent H-2q (I-Aq) restriction on the early development of high levels of IgG1 antibody to E/S antigen was revealed by ELISA. No such restriction was demonstrated for the specific IgG2a response patterns. Recognition of two high molecular weight antigens (90-95 kDa, 105-110 kDa) by IgG antibodies was also shown to be almost exclusively H-2q restricted and may be related at least in part to the high antibody levels seen for H-2q strains of mice. Immune serum from resistant (B10.BRxB10.G) F1 hybrid mice (H-2q/k) containing high levels of IgG1 antibodies specific for T. muris E/S and IgG antibodies which recognized the 90-95 kDa and 105-110 kDa E/S antigens was effective in transferring protection to the non responsive B10.BR mouse strain as seen on day 35 post-infection (p.i.). It is suggested that the IgG responses described for the generally very resistant H-2q mouse strains may contribute to, but not be an absolute requirement for, protective immunity, antibody-mediated damage facilitating a subsequent cellular attack in certain strains of mice. PMID- 2255563 TI - Monoclonal antibodies against Opisthorchis viverrini antigens. AB - Monoclonal antibodies (MoAb) were produced against somatic antigens of adult human liver fluke Opisthorchis viverrini. Earlier studies attached diagnostic potential to an 89-90 kD antigen present in both somatic extracts and in vitro culture supernatants as well as to the abundant 16-17 kD tegumental protein doublet. Mice made excellent immune responses to low dose somatic extract adsorbed onto nitrocellulose or to the 80-95 kD region of SDS gel Western blots. The antigen specificities of hybridomas reactive with somatic antigen by ELISA were determined by radioimmunoprecipitation or immunoblotting. Six MoAb reacted with the desired 16 kD tegumental protein. A 90 kD somatic protein was identified by 9 clones. By indirect immunofluorescence, monoclonals reactive with the 16 kD polypeptide identified the outermost surface of the tegument. The 90 kD antigen was associated with all major muscle systems, most strikingly the crossed subtegumental layers, oral and ventral suckers, pharynx and a thin layer surrounding caeca. The biochemical identity of this muscle-associated antigen is unknown, but it is clearly distinct from the previously identified species specific 89 kD exoantigen. The 16 kD tegumental protein shares epitopes with a number of related flukes. However, 2 MoAb which react with this protein show no crossreaction. PMID- 2255564 TI - Emulation of conduction system functions in the hearts of early mammalian embryos. AB - The conduction system functions of atrioventricular sequential contractions, atrioventricular delay, and coordination of ventricular contraction were examined in rat embryos at the earliest functional stage of cardiac development (before cardiac looping, n = 6) and shortly after looping (n = 15). Atrioventricular sequential contractions were observed in all embryos, and contractions appeared to originate in the left sinus horn. Atrioventricular delay was present in both prelooped (132 +/- 32 ms) and looped (141 +/- 15 ms) hearts. Before looping, contractions traveled from proximal ventricle to bulbus cordis, a distance of 253 +/- 27 microns, in 72 +/- 22 ms. After looping, contractions crossed an increased intraventricular distance (520 +/- 28 microns, p less than 0.005) in substantially less time (16 +/- 7 ms, p less than 0.005). Sinoatrial and atrioventricular nodal functions are emulated in both prelooped and looped hearts of early mammalian embryos, and His-Purkinje system function is emulated in looped hearts. PMID- 2255565 TI - The effects of the patent ductus arteriosus on diaphragmatic blood flow and function. AB - Decreased diaphragmatic blood flow (Qdi) is associated with decreased contractility in adult animals. To see whether the decrease in Qdi associated with a patent ductus arteriosus was associated with a decrease in diaphragmatic contractility (Pdi), we prepared 11 near-term fetal lambs by infiltrating the ductus with formalin and placing a snare around it to regulate its patency. The lambs (with open chest) were delivered and mechanically ventilated, and the phrenic nerves and diaphragm were paced (using transvenous wires) at rates of 20/min, 60/min, and 100/min (Inspiratory time/total respiratory cycle time = 0.5) for 7-min contraction periods after 30-min recovery periods. Qdi was measured with radiolabeled microspheres at the end of each contraction period. Diaphragmatic performance was determined by comparing Pdi at the start (Pdi start) and end (Pdi-end) of the contraction period. When the ductus was closed, Qdi increased 6.9-fold at 20/min and 9.8-fold at 100/min (compared with Qdi at rest). Pdi-end was less than Pdi-start at all contraction rates, but the reduction was significantly greater at 100/min (Pdi-end/Pdi-start: 0.80 +/- 0.10 at 20/min; 0.67 +/- 0.17 at 100/min). Pdi-start also decreased with increasing rates of contraction. When the ductus was open, the left-to-right shunt was 64 +/ 11% of left ventricular output. Qdi in the unpaced diaphragm was significantly reduced (open 4.0 +/- 3.8 versus closed, 7.4 +/- 2.4 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255566 TI - An automated bedside method for measuring functional residual capacity by N2 washout in mechanically ventilated children. AB - Beside measurement of functional residual capacity (FRC) in ventilated children is impractical. Using a simple technique based on open circuit N2 washout, we measured FRC in ventilated children. The system was evaluated in the laboratory and in patients. Using a mechanical lung, the reproducibility of 200 studies over a range of 100-500 mL at each of four different flow rates (10 determinations at each level) was very high with a mean coefficient of variation of 2.3% (range 0.5 5.1%). Linearity of the integrated N2 signal for volumes of 100-500 mL washed out at different flow rates was excellent (range 7.4-17.9 L/min), r = 0.99. The mean difference between measured and preset mechanical lung volumes was 2.4% (range 0 4.6%). In vivo, reproducibility of six to 10 FRC determinations in each of 30 children gave a mean coefficient of variation of 2.7%. Comparison to the conventional Douglas bag collection method showed a high correlation (r = 0.97). We conclude that this is an easy, highly reproducible, and accurate method for FRC determination suitable to ventilated infants and children. PMID- 2255567 TI - Functional residual capacity in ventilated infants and children. AB - Positive end expiratory pressure (PEEP) is an accepted treatment for children with acute respiratory failure secondary to restrictive lung diseases. Using a simple technique based on open circuit nitrogen washout, we determined the functional residual capacity (FRC) in 25 ventilated children (age 3 wk-10 y) with acute respiratory failure secondary to restrictive lung disease (pulmonary edema, bilateral pneumonia). FRC measured at a physiologic level of PEEP (2-4 cm H2O) was 45.0 +/- 3.6% (mean +/- SEM; range 12-80%) lower than normal predicted values. At the PEEP level chosen clinically (4-10 cm H2O, mean = 6.0), the FRC was below normal predicted values for nonintubated children by a mean of 31.8% (range 0-73%) (p = 0.0001) and only seven patients (28%) had FRC within 20% below predicted normal values. FRC normalized at PEEP levels of 6-18 cm H2O (mean = 11.6), which was up to 200% above the clinically chosen PEEP level. In six children without lung disease who were ventilated at a PEEP level of 2-4 cm H2O, the FRC was within normal range in two, but significantly higher (by 45%) in the other four. We conclude that FRC in ventilated children with acute restrictive lung disease is significantly lower than normal and the clinically chosen PEEP fails to normalize the FRC in most of the cases. PMID- 2255568 TI - Role of renal interstitial hydrostatic pressure in the blunted natriuretic response to saline loading in the piglet. AB - Acute saline volume expansion (VE) in the developing animal is associated with a blunted natriuretic response when compared with that in adults. Recent studies have suggested that renal interstitial hydrostatic pressure (RIHP) plays an important role in mediating VE-induced natriuresis in the adult. The purpose of our study was to determine whether abnormalities in the RIHP response to VE could be involved in the blunted natriuretic response in the developing animal. The effect of an acute saline load (5% body wt) on RIHP and sodium excretion was examined in adult pigs (greater than 70 d) and piglets (26-43 d). In response to an acute saline load, the piglets excreted significantly less sodium than the adults (1.7 +/- 0.5 versus 3.8 +/- 0.7 mumol/min/g kidney wt). The increase in fractional excretion of sodium in response to VE was also significantly less in the piglets. There was no significant change in GFR in either group. Associated with the blunted natriuretic response in the piglet was an absence of an increase in RIHP (6.1 +/- 1.1 versus 6.1 +/- 1.6 mm Hg) in response to VE. In contrast, the adult pig, which exhibited a normal natriuretic response, showed a significant increase in RIHP (8.8 +/- 1.3 to 12.3 +/- 1.5 mm Hg) during VE. When RIHP was prevented from increasing during VE in the adult pigs, the natriuretic response was significantly attenuated, as it was in the piglets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255569 TI - Uterine artery ligation in the maternal rat alters fetal tissue glucose utilization. AB - We studied the effects of maternal uterine artery ligation on fetal rat tissue glucose utilization (GU). Unilateral uterine artery ligations were performed on the 19th d of gestation (term 21.5 d) and 2-[3H]deoxy-D-glucose was used to measure GU of placenta, liver, brain, muscle, kidney, and heart from fetuses in the ligated (IUGR) and nonligated (control) uterine horns 24 and 48 h after the procedure. At both periods, IUGR fetuses weighed significantly less and had lower fetal/maternal plasma glucose ratios than controls. Twenty-four h after ligation, placenta, liver, brain, and muscle from IUGR fetuses had lower relative GU rates than corresponding tissues from control fetuses (p less than 0.01-0.05). However, at 48 h, IUGR liver, muscle, kidney, and heart had higher relative GU rates than control tissues (p less than 0.01-0.05). The lower GU of IUGR fetal tissues observed at 24 h postligation was likely related to the acute decrease in fetal glucose availability. Other factors, such as hypoxemia and acidosis, that affect cellular metabolism may also have led to lower GU rates. The increase in GU by IUGR tissues at 48 h occurred despite a persistence of low fetal glucose concentrations and can be explained by either: 1) an attempt by IUGR fetal tissues to compensate for the persistently low plasma glucose; 2) an increased demand for metabolic fuel for repair processes; or 3) a less efficient use of glucose due to alterations in cellular respiration. We speculate that this increase in fetal tissue GU may be partially responsible for the supranormal glucose requirements seen in small-for-gestational-age newborns. PMID- 2255571 TI - Hypoxanthine, xanthine, and uric acid concentrations in the cerebrospinal fluid, plasma, and urine of hypoxemic pigs. AB - The concentrations of hypoxanthine, xanthine, and uric acid in plasma and cerebrospinal fluid (CSF), as well as the urinary output of hypoxanthine and xanthine, were measured in four groups of pigs (three groups with different degrees of hypoxemia and one control group). During hypoxemia with arterial O2 tension between 2.1 and 3.0 kPa [group 1, fractional inspired oxygen (FiO2) = 0.08], hypoxanthine increased in CSF from a mean basal value of 18.1 to 39.3 mumol/L at death (p less than 0.02), in plasma from 25.4 to 103.6 mumol/L (p less than 0.05), and in urine from 21.3 to 87.1 nmol/kg/min (p less than 0.02). Xanthine changed in a similar way: in CSF from 4.0 to 10.6 mumol/L (p less than 0.02), in plasma from 0.7 to 48.1 mumol/L (p less than 0.02), and in urine from 4.0 to 12.6 nmol/kg/min (p less than 0.05). Uric acid increased in CSF from 2.7 to 11.6 mumol/L (p less than 0.05), and in plasma from 15.4 to 125.0 mumol/L (p less than 0.02). During hypoxemia with arterial O2 tension between 3.0 and 4.0 kPa (group 2, FiO2 = 0.11), hypoxanthine increased in the CSF from 14.7 to 42.9 mumol/L (p less than 0.02). Plasma hypoxanthine increased from 20.3 to a maximum of 44.1 mumol/L (p less than 0.02), but decreased to initial values by the time of death. The urinary excretion of hypoxanthine increased from 13 to 54 nmol/kg/min (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255570 TI - Psychosine cytotoxicity in rat neural cell cultures and protection by phorbol ester and dimethyl sulfoxide. AB - In Krabbe's disease (globoid cell leukodystrophy), galactosylsphingosine (psychosine) is considered to be a causative agent of the pathology found in the nervous system of the patients. In our study, we examined the cytotoxic effect of psychosine in neural cell cultures derived from the rat nervous system. The concentration of toxic thresholds varied from cell type to cell type. The 50% of toxic doses for oligodendrocytes, astrocytes, and the sensory neurons of the dorsal root ganglia were 8, 20, and 30 micrograms/mL, respectively. Oligodendrocytes, therefore, appeared to show a higher sensitivity to psychosine than did astrocytes or neurons. When phorbol ester or DMSO was applied simultaneously with psychosine as protective agents in enriched cultures of rat oligodendrocytes, the total number of live cells and galactocerebroside-positive cells and the 2'3'-cyclic nucleotide 3'-phosphohydrolase activity in these cultures were considerably higher as compared with their levels in the experimental cultures treated with psychosine alone. These results indicate that phorbol ester and DMSO could serve as protective agents for psychosine neurotoxicity. PMID- 2255572 TI - Changes in oxypurine concentrations in vitreous humor of pigs during hypoxemia and post-mortem. AB - In the vitreous humor from three hypoxemic and one control group of pigs, hypoxanthine, xanthine, and uric acid concentrations were measured. The purine concentrations were measured before the hypoxemia, at the time of death, and 24 h post-mortem. During hypoxemia with arterial O2 tension between 2.1 and 3.0 kPa [fractional inspired oxygen (FiO2) = 0.08], hypoxanthine concentrations increased from a mean basal value of 11.7 +/- 5.6 mumol/L to 16.3 +/- 2.4 mumol/L at the time of death (NS). Xanthine concentrations changed from a basal value of 0.3 +/- 0.1 mumol/L to 0.6 +/- 0.2 mumol/L (p less than 0.02), and uric acid changed from 3.4 +/- 1.1 mumol/L to 5.0 +/- 4.5 mumol/L (NS). During hypoxemia with arterial O2 tension between 3.0 and 4.0 kPa (FiO2 = 0.11), hypoxanthine increased in the vitreous humor from a mean basal value of 9.1 mumol/L to 20.3 mumol/L at the time of death (p less than 0.02). Xanthine concentrations increased from 0.3 mumol/L to 1.3 mumol/L (p less than 0.05), whereas there was no change in uric acid concentration (basal 5.0 +/- 0.8 mumol/L and final 4.5 +/- 1.0 mumol/L). During milder hypoxemia with arterial O2 tension between 4.3 and 5.6 kPa (FiO2 = 0.14), or in the control group (FiO2 = 0.21), neither of the metabolites changed significantly. The vitreous humor was not stable post-mortem, inasmuch as the mean concentration of hypoxanthine increased from 18.2 +/- 7.7 mumol/L to 121.6 +/- 57.4 mumol/L 24 h post-mortem (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255573 TI - Effect of dietary omega-3 fatty acids on retinal function of very-low-birth weight neonates. AB - Retinal function was assessed by electroretinogram in 32 neonates randomly assigned to formulas of different omega-3 fatty acid content and in 10 infants fed human milk. All neonates had a birth weight of 1000-1500 g and were fed study diets from d 10 to 45 or discharge. Group A received formula containing predominantly 18:2 omega-6. Group B received a balanced mix of 18:2 omega-6 and 18:3 omega-3. Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 omega-3 content similar to that of human milk. The fatty acid composition of plasma and red blood cell (RBC) lipids were similar for all groups on entry but marked diet-induced differences were found after feeding the study diets. Group C was comparable to the human milk-fed group, but group A had lower 22:6 omega-3 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in plasma and RBC membranes. Cone function was not affected by dietary essential fatty acids. Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC omega-3 LCPUFA (r = 0.63, p less than 0.0001); 44% of the variance could be explained by RBC and plasma omega-3 LCPUFA content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255574 TI - Postnatal surge in serum calcitonin concentrations: no contribution to neonatal hypocalcemia in infants of diabetic mothers. AB - It has been suggested that hypercalcitoninemia may contribute to neonatal hypocalcemia in infants of diabetic mothers (IDM). Because the role of calcitonin (CT) in Ca metabolism in humans is questionable, we hypothesized that serum CT peaks similarly after birth in IDM and controls and that serum Ca concentrations do not correlate with serum CT. Forty-seven term IDM (White classes B-RT) were compared with 31 controls. Controls were born after normal pregnancies, labors, and deliveries. Blood samples (cord and 24 h) were analyzed for Ca, Mg, parathyroid hormone (PTH), and CT. Repeated measures analysis showed increasing serum Mg, PTH, and CT, and decreasing Ca over time. The incidence of hypocalcemia was significantly higher in the diabetic group (p less than 0.01) and the incidence of hypomagnesemia was borderline significantly higher (p less than 0.06). There were no differences in cord or 24-h serum concentrations of CT between groups. In multiple regression analysis, serum Ca and PTH were correlated (p less than 0.02, R2 = 0.33), but not serum Ca and CT; the increase in serum PTH in relation to serum Ca at the nadir (24 h) correlated directly with serum Mg concentrations (R2 = 0.31, p less than 0.05). Thus, serum CT increases after birth irrespective of the rate of decrease of serum Ca in both IDM and controls; high CT concentrations observed after birth (as compared with adult norms) do not seem to play a role in the pathogenesis of neonatal hypocalcemia in IDM; and responsiveness of parathyroid gland at birth is adversely affected by hypomagnesemia, which supports the theory of functional hypoparathyroidism in Mg deficiency. PMID- 2255575 TI - Hypothalamic-pituitary-ovarian function in menstruating women with Turner syndrome (45,X). AB - The hypothalamic-pituitary-ovarian hormone secretion patterns were evaluated in two women with 45,X Turner syndrome, spontaneous sexual development, and monthly menstrual periods. Each women had serum gonadotropin and sex steroid determinations during two or more menstrual cycles. During the follicular phase of a menstrual cycle, both women received 100 micrograms gonadotropin-releasing hormone (GnRH) s.c., and serum LH and FSH responses were determined. In addition, one woman collected daily overnight urine specimens for 40 consecutive days, spanning two menstrual periods, for the measurement of LH, FSH, estriol, and free progesterone. The randomly measured hormone results showed low serum progesterone concentrations during luteal phases, consistent with the interpretation of anovulation or inadequate corpus luteum function. At the time of the GnRH stimulation tests, baseline serum FSH concentrations and FSH responses to GnRH were within normal limits, whereas baseline LH levels and LH responses to GnRH were low. The pituitary gonadotropin secretion patterns were more consistent with patterns seen during early puberty than in the perimenopausal state. This interpretation was further confirmed by the urinary excretion patterns of gonadotropins, which were not significantly elevated. Furthermore, the urinary hormone profiles revealed that, although the intermenstrual period was of normal length, the follicular phase was prolonged, with normal levels of LH, FSH, and estriol excreted. The menstrual cycle studied was ovulatory but had a short luteal phase. The hormone results indicated that the dysgenetic ovary of women with 45,X Turner syndrome is capable of producing sufficient quantities of sex steroids and other regulatory factors to maintain gonadotropin secretion patterns that are reminiscent of early puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255576 TI - 3-Oxothiolase activities and [14C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency. AB - Cultured fibroblasts from 13 patients with organic aciduria suggesting 3 oxothiolase deficiency were studied by measuring first the capacity of the isoleucine degradative pathways in whole cells, as the incorporation of 1-[14C]-2 methylbutanoic acid into macromolecules, and, second, the activity of 3 oxothiolase in cell homogenates using specific 3-oxoacyl-CoA substrates to identify the different enzymes. Nine patients showed low incorporation by the macromolecular labeling assay, as well as deficiency of 2-methylacetoacetyl-CoA thiolase. In this group of patients, low activity by the macromolecular labeling assay was associated with clinically severe symptoms, and vice versa. Two patients showed reduced macromolecular labeling, but apparently normal 3 oxothiolase. Finally, two patients showed normal activities by either test, the reason for their particular organic aciduria being unknown. In conclusion, occurrence of urinary 2-methyl-3-hydroxybutyric acid and/or tiglyglycine is not an unequivocal indicator of the absence of the thiolase that metabolizes 2 methylacetoacetyl-CoA. Measurement of 1-[14C]-2-methylbutanoic acid incorporation in cultured fibroblasts adds important information in studying possible defects of the isoleucine catabolic pathway. PMID- 2255577 TI - Heteroplasmy in chronic external ophthalmoplegia: clinical and molecular observations. AB - Chronic progressive external ophthalmoplegia (CPEO) describes a recognizable clinical syndrome frequently associated with variable dysfunction in other organ systems. Histochemical and biochemical studies suggested primary dysfunction of oxidative phosphorylation. This has recently been confirmed by demonstration of partially deleted as well as normal mitochondrial DNA--heteroplasmy--in some of these patients, most of them sporadic. In the six heteroplasmic CPEO patients that we have examined to date, the partially deleted species has been detected in all tissues tested, albeit in vastly different proportions. We report here detection of physiologically significant proportions of partially deleted mitochondrial DNA in several organs taken at autopsy from a CPEO patient with severe multisystem disease. We discuss the relationship of CPEO to several other clinical phenotypes associated with mitochondrial dysfunction, and discuss the possible implications of heteroplasmy for the development of variable phenotypes. PMID- 2255578 TI - Utilizing the nursing process in the development of a medication group on an inpatient psychiatric unit. AB - The nursing process guided the development of a medication group for psychiatric clients on an inpatient psychiatric unit. The group was established to provide clients with the basic medication information that they are entitled to as consumers of health care. Procedures used to develop the group are discussed in this article. Evaluation procedures suggest that the medication group enhanced clients' knowledge, fostered their self-care, and provided the nursing staff with the opportunity to expand its health-teaching skills. PMID- 2255579 TI - The dopamine hypothesis of schizophrenia. AB - While many theories of schizophrenia have been explored, recent research has focused on the possible role that dopamine may play in the causation of this complex disease. After reviewing a clinical description of schizophrenia, this discussion reviews the normal physiology of dopamine, proposed pathological mechanisms, and clinical implications. PMID- 2255580 TI - Seclusion: a last resort measure. AB - The practice of secluding patients after violent incidents has long been a treatment used by mental health nurses. While seclusion keeps the patient from further self-inflicted pain and restores normalcy to the unit, the practice often sets up an unending cycle of negative behavior. Other methods of dealing with the violent patient are explored in this article, including early intervention by nurses, ignoring the outburst, separating the disruptive person for a shorter time, and speaking gently with the client. The conclusion reached is that nurses must keep in mind the goal: to help the patient reintegrate into the group as safely and quickly as possible. PMID- 2255581 TI - Tardive dyskinesia: a key issue facing the psychiatric/mental health nurse. AB - The use of psychotropic drugs over the past four decades has helped calm violent behavior in psychiatric patients. However, a significant number of patients using these drugs have developed tardive dyskinesia, a potentially irreversible neurological syndrome that causes a variety of involuntary movements of the head, face, and body. The nurse can play a large role in structuring a written informed consent document and a well-coordinated TD monitoring system to protect patients and prevent lawsuits. PMID- 2255582 TI - Whose practice is it anyway? PMID- 2255583 TI - Safe and sound: orienting nurses to psychiatry. AB - Nurses without prior psychiatric experience need to acquire certain information and skills if they are to practice with a sense of competence as they begin their careers in psychiatric/mental health nursing. Essential content for a suggested orientation program includes: key theoretical concepts; maintenance of a safe environment; and interacting with clients who are delusional/hallucinating, behaving seductively, or are suicidal. The importance of clinical supervision is addressed. PMID- 2255584 TI - Artemisia annua L.: a source of novel antimalarial drugs. AB - Artemisia annua L. contains artemisinin, an endoperoxide sesquiterpene lactone, mainly in its leaves and inflorescences. This compound and a series of derivatives have attracted attention because of their potential value as antimalarial drugs. In this review a survey of the currently available literature data is given. It includes phytochemical aspects, such as constituents of A. annua, the artemisinin content during the development of the plant and its biosynthesis, isolation, analysis and stability. Total chemical synthesis of artemisinin is referred to, as well as structure-activity relationships of derivatives and simplified analogues. Pharmacological studies are summarized, including the mechanism of action, interaction of the antimalarial activity with other drugs, possible occurrence of resistance to artemisinin, clinical results, toxicological aspects, metabolism and pharmacokinetics. Finally, plant cell biotechnology is mentioned as a possible means to obtain plants and cell cultures with higher artemisinin contents, allowing an industrial production of pharmaceuticals containing this novel drug. PMID- 2255586 TI - Comparative bioavailability study of two brands of prazosin-containing tablets in healthy volunteers. AB - The bioavailability of two prazosin formulations was studied in 12 healthy volunteers. 1 Subject left the study. Based on the statistical tests of the pharmacokinetic parameters of prazosin in 11 volunteers, such as t 1/2, Cmax, tmax and AUC, it could be concluded that both preparations had comparable bioavailabilities. PMID- 2255585 TI - Decreased ciprofloxacin absorption with concomitant administration of ferrous fumarate. AB - The effect of ferrous fumarate on the relative bioavailability of ciprofloxacin after a single 500 mg oral dose of ciprofloxacin was studied in eight healthy males. Blood samples were collected at regular intervals 0-24 h post-dose. Urine was collected during 24 h to determine the cumulative urine excretion of ciprofloxacin. Ciprofloxacin concentrations in serum and urine were determined by high pressure liquid chromatography. Mean area under the serum concentration-time curve decreased significantly (P less than 0.001) after ciprofloxacin was taken with 200 mg ferrous fumarate. The relative bioavailability was 30% when ciprofloxacin was given with ferrous fumarate. The maximum blood level decreased from 2.1 +/- 0.9 (control) to 0.6 +/- 0.2 mg/l (with ferrous fumarate). Further studies are needed to determine if chronic treatment with ferrous fumarate further decreases the relative bioavailability. For the moment administration of ciprofloxacin with ferrous fumarate should therefore be avoided. PMID- 2255587 TI - Comparison of clonazepam sorption to polyvinyl chloride-coated and polyethylene coated tubings. AB - The sorption of clonazepam to polyvinyl chloride tubing, polyethylene-coated tubing and to a polyethylene syringe was determined. Pumping of clonazepam (5 mg/48 ml) through the polyvinyl chloride tubing with flow rates of 2 ml/h and 4 ml/h resulted in a reduction of the clonazepam concentration to about 40% and 55% of the original strength after 0.6 h, respectively. This value was 55% at a flow rate of 2 ml/h and a clonazepam concentration of 10 mg/48 ml. The effluent clonazepam concentration increased gradually after an infusion period of 1 h. Sorption of clonazepam to the polyethylene syringe and to the tubing coated on the inside with polyethylene does not occur. The use of polyethylene-coated administration sets is recommended for intravenous administration of clonazepam. PMID- 2255588 TI - Quantitative determination of particulate contamination in intravenous administration sets. AB - Particle counts were performed on 1,000 intravenous administration sets from ten suppliers on the Swiss market using a HIAC/Royco electronic counter. The following main conclusions may be drawn from the results of this study: --the small particles were the most numerous, regardless of the type of set; --the differences in the counts obtained for the different suppliers' sets tended to level off for particles larger than 10 microns; --the drip chamber and latex connector may be two important sources of particles; --the particulate contamination from the sets is relatively low compared with the amount of particles contained in the parenteral solutions. PMID- 2255589 TI - Decomposition of pilocarpine eye drops assessed by a highly efficient high pressure liquid chromatographic method. AB - A rapid high-resolution high pressure liquid chromatographic method was developed for assaying pilocarpine. Pilocarpine in ophthalmic solutions decomposes fairly rapidly to give isopilocarpine, pilocarpic acid and isopilocarpic acid. The quality of an ophthalmic solution can be assessed by assaying these decomposition products. Existing high pressure liquid chromatographic methods suffer from long analysis times and poor resolution. The new method uses as the mobile phase 6 ml/l of triethylamine in water (pH 2.3, adjusted with 85% phosphoric acid) at a flow of 1.5 ml/min and as the stationary phase a C18-silica 125 x 4.6 mm column. 2-Amino-1-phenyl-1,3-propanediol is used as an internal standard. Complete separation was obtained within 8 min. Pilocarpine eye drops were stored under different conditions and then analysed for decomposition products. During heat treatment, decomposition to isopilocarpine predominated over decomposition to pilocarpic or isopilocarpic acid. However, when stored at room temperature or in a refrigerator, formation of pilocarpic acid clearly prevailed. Thus, from assessment of decomposition products, the cause of decomposition can be established. PMID- 2255590 TI - Dissolution profiles of mesalazine formulations in vitro. AB - In vitro dissolution profiles of three controlled-release mesalazine formulations were determined at pH 1.0, 6.0 and 7.5. A closed-column type dissolution apparatus was used. A reproducible gradual dissolution profile was seen for Pentasa at all pH values. Dissolution starts immediately and is complete after 20 h. Dissolution profiles at pH 1 and pH 7.5 are much alike and dissolution is faster than at pH 6. The behaviour of Asacol at different pH values corresponds with the expectations: no release at pH 6 and pH 1, fast release at pH 7.5. Dissolution starts after 1 h and is complete after 3 h. Mesalazine release from Salofalk tablets at pH 7.5 and pH 6.0 starts after 2 and 3 h, respectively, and is complete after 5 and 10 h. However, after a long lag-time (10 h) mesalazine is also released from Salofalk tablets at pH 1 and dissolution is complete after 23 h. PMID- 2255591 TI - HIV link to bad drug reactions. PMID- 2255592 TI - The art of well-being. PMID- 2255593 TI - Village life? PMID- 2255594 TI - Regional studies. PMID- 2255595 TI - Kindred spirits. PMID- 2255596 TI - The Thatcher legacy. PMID- 2255598 TI - Health promotion. Working together. PMID- 2255597 TI - Health promotion. Patient power. PMID- 2255600 TI - Skills on tape. PMID- 2255601 TI - European round-up. PMID- 2255599 TI - Health promotion. Information all the way. PMID- 2255602 TI - The long and winding road. PMID- 2255603 TI - Fair deal on appeal. Wading through mud. PMID- 2255604 TI - Frankenstein's nurse. PMID- 2255605 TI - A mutually beneficial relationship. Care study. PMID- 2255606 TI - Nurses and the law. Ethics in practice. PMID- 2255607 TI - Stoma care. Eye of the beholder. PMID- 2255609 TI - Midwives'. Aiming for the stars. PMID- 2255608 TI - Stoma care. Circles of support. PMID- 2255610 TI - Alternative antenatal treatments. PMID- 2255611 TI - Midwives'. Managing without drugs. PMID- 2255612 TI - US staff forced to take AZT. PMID- 2255613 TI - Children in need. PMID- 2255614 TI - Special delivery. PMID- 2255615 TI - Crushed by the system? PMID- 2255616 TI - Our Glad. PMID- 2255617 TI - Mental handicap. Fit for the future. PMID- 2255618 TI - Mental handicap. The case for reform. PMID- 2255619 TI - Mental handicap. Getting on with the job. PMID- 2255620 TI - Nurses' homes. More home work needed. PMID- 2255621 TI - Making sense of .... bone densitometry. PMID- 2255623 TI - What did you do in the '80s? PMID- 2255622 TI - Care and companionship. Care study. PMID- 2255624 TI - Education. Island of innovation. PMID- 2255625 TI - Investigating infection acquired in hospitals. PMID- 2255626 TI - Benzodiazepines and unilateral ECT. PMID- 2255627 TI - Investigating students learning experiences. PMID- 2255628 TI - Nurse practitioners in accident and emergency. PMID- 2255629 TI - Nurse education. Stress ... are you affected? PMID- 2255630 TI - How to ... use questionnaires. PMID- 2255632 TI - Hazards in hoists. PMID- 2255631 TI - From pestilence to asepsis. PMID- 2255633 TI - Catheterisation under scrutiny. PMID- 2255634 TI - Tears and fears. PMID- 2255635 TI - A well-loved service. PMID- 2255636 TI - Poole Forecast. Interview by Toni Turner. PMID- 2255637 TI - A wee problem. PMID- 2255638 TI - Bleak outlook. PMID- 2255639 TI - Ghosts of Christmas past. PMID- 2255640 TI - It still makes me cringe. PMID- 2255641 TI - Spiritual services. PMID- 2255643 TI - Living in fear of food. PMID- 2255642 TI - Season without strife. PMID- 2255644 TI - A total loss of control. PMID- 2255645 TI - Double dilemma. Care study. PMID- 2255646 TI - Midwifery in China. PMID- 2255647 TI - Systems of life. The cardiovascular system. Part II. PMID- 2255648 TI - Testing a hydrocolloid. PMID- 2255649 TI - Dressing cavities. PMID- 2255650 TI - Observations in outpatients. PMID- 2255651 TI - [Classification of chronic pancreatitis]. PMID- 2255652 TI - [Diagnosis of diabetes mellitus and disorders of glucose tolerance in patients after acute pancreatitis]. AB - The study aimed at evaluating an incidence of diabetes mellitus and carbohydrate tolerance disorders as well as insulinemia in patients with the history of the acute pancreatitis. Baseline glycemia was determined in 50 patients with a history of the acute pancreatitis and in 15 healthy individuals (aged between 18 and 65 years). Blood sugar was then determined 30, 60, 90 and 180 minutes following loading with 75 g of glucose. Fasting insulinemia and that following loading with 75 g glucose were determined at the same time period. Diabetes mellitus was diagnosed in 6 patients (12%) whereas carbohydrate tolerance in 4 patients (8%). A decrease in insulin response to carbohydrates was noted in 36 patients (72%) with a history of the acute pancreatitis in comparison with the control group. The obtained results suggest that the acute pancreatitis significantly decreases endocrine functioning of the pancreas. Therefore, metabolism of carbohydrates should be checked particularly in the individuals with a history of the acute pancreatitis without the symptoms of both diabetes mellitus and sugar tolerance disorders but with the signs of decreased insulin response to carbohydrates. PMID- 2255653 TI - [Cellular immunity in insulin-dependent diabetes mellitus (type 1)]. AB - Cell-mediated immunity was investigated with T-cell blastic transformation stimulated by phytohaemagglutinin and/or insulin in patients with diabetes mellitus type 1. T-cell blastic transformation was determined in the whole blood by the intake of labelled thymidine intake by the lymphocytic DNA. Healthy individuals and patients with diabetes mellitus type 2 served as control groups. It was found that T-cell blastic transformation stimulated with phytohaemagglutinin is markedly diminished in patients with diabetes mellitus type 1 and to a lesser degree in patients with diabetes mellitus type 2. Insulin increased T-cell blastic transformation in insulin-dependent diabetic patients but has no effect in diabetes mellitus type 2. The obtained results suggest that induction and central phases of the cell-mediated immunological response are diminished in diabetes mellitus independently on its type. Such disorders may have different etiology depending on the type of diabetes mellitus. PMID- 2255654 TI - [Effect of beta-adrenergic blockade on cortisol secretion in insulin-induced hypoglycemia in animals with experimental diabetes mellitus]. AB - An effect of the selective beta-adrenergic block with metoprolol and non selective beta-adrenergic block with propranolol on the hypoglycaemia was investigated in 30 dogs of the control group and 30 dogs with alloxan diabetes. A significant increase in cortisol secretion was seen in the insulin-induced hypoglycaemia in both groups without beta-adrenergic block. It suggests an important role of cortisol in the normalization of glycaemia following an administration of the exogenous insulin. Beta-adrenergic block, especially with metoprolol, produces a significant increase in cortisol secretion confirming the report on direct effect of this beta-adrenolytic agent on cortisol secretion. PMID- 2255655 TI - [Evaluation of nutrition of obese patients]. AB - An analysis of the nutrition was carried out in 50 obese subjects with questionnaire technique. It was found that moderately obese patients received an excess of calories in comparison with the standards and requirements but approximately 25% of the obese subjects of this group was adequately fed. One of the important nutritive errors in the examined obese subjects was significant percentage of fat in the daily ration and relatively low content of the complex carbohydrates. Nutrition might be considered high-protein++. Obese subjects frequently eat irregularly, and ate between meals, especially sweets. PMID- 2255656 TI - [Cytoplasmic islet-cell antibodies (ICA) and cytoplasmic complement- fixing antibodies (CF-ICA) in patients with newly detected and short-lasting diabetes mellitus type 1]. AB - The study aimed at assessing ICA and CF-ICA in the serum of patients with newly diagnosed and short-lasting diabetes mellitus type 1. Sixty patients with newly diagnosed diabetes type 1 (39 patients) and short-lasting diabetes of the same type (21 patients) aged between 2 and 34 years were classified. Anti-islet antibodies were detected with indirect immunoflourescence in specimens of fresh, frozen human pancreast in the tested group ICA were found in 53% of cases. At the time of diagnosis, ICA were found in 76% of children and in 14% of adult patients whereas respective data for diabetes mellitus lasting up to 2 years were 40% and 64%. Complement-fixing islet cytoplasmatic antibodies were found only in patients with ICA (47% of such cases). These antibodies were found in children with newly diagnosed diabetes mellitus (36%). In case of adults CF-ICA were detected in 7% of newly diagnosed diabetes mellitus cases and in 45% of cases with the disease lasting for 2 years. Titres of ICA ranged from 1:1 to 1:128 whereas titres CF-ICA from 1:1 to 1:8. No correlation between ICA titre and CF-ICA titre was noted. PMID- 2255657 TI - [Adverse effects of oral hypoglycemic drugs in elderly patients]. PMID- 2255658 TI - [Cystic fibrosis--a disease of children and adults]. PMID- 2255659 TI - [Effect of beta-adrenergic blockade on glucose homeostasis in insulin-induced hypoglycemia during physiological processes in diabetes mellitus]. PMID- 2255660 TI - [New data on the regulation of glucose transport to skeletal muscle cells]. PMID- 2255661 TI - The effect of amiloride on the cardiac chronotropic responses to isoproterenol in myocardial aggregate cells in culture. AB - The purpose of this study was to test the hypothesis that amiloride alters the response of cardiac myocytes to isoproterenol. Myocardial cell aggregates were prepared from 7 day-old chick embryos maintained in culture for 72 hrs before study. Isoproterenol, 10-8 M to 10-5 M, significantly (P less than 0.05) increased contractile frequency of myocardial aggregates. The effects of isoproterenol were maximum within 5 min. of exposure and declined thereafter. In the absence of isoproterenol, amiloride, at 10-6 M and 10-7 M produced a transient decrease in contractile frequency while amiloride at 10-5 M produced a significant (P less than 0.05) decrease in contractile frequency. Amiloride significantly (P less than 0.05) increased the effect of isoproterenol on cardiac contractile frequency. There was a greater and more sustained response to isoproterenol in the presence of amiloride. Furthermore, the magnitude of these effects were greater with higher concentrations of amiloride. These data indicate that amiloride accentuates the cardiac chronotropic response to isoproterenol and suggest that, because amiloride inhibits sodium entry in these cells, change in intracellular sodium may be one of the mechanisms mediating the chronotropic action of isoproterenol on the heart. PMID- 2255662 TI - Antagonism of acetaminophen-induced hepatocellular destruction by trifluoperazine in mice. AB - The effect of trifluoperazine, a specific calmodulin inhibitor, on hepatocellular destruction induced by acetaminophen was investigated in mice. Trifluoperazine 30 mg/kg administered intraperitoneally 30 min. or 0 min. before acetaminophen blocked hepatocellular destruction induced by the hepatotoxin, as evidenced by the determination of plasma GPT activity. Trifluoperazine also completely inhibited an increase of calcium contents in liver induced by acetaminophen administration. Furthermore, the increase of hepatic phosphorylase a activity induced by acetaminophen administration was completely abolished by pretreatment with trifluoperazine. However, hepatic glutathione depletion induced by acetaminophen was not prevented by pretreatment with trifluoperazine. Trifluoperazine administration caused a marked decrease in the body temperature of acetaminophen-treated animals. However, when the trifluoperazine-treated acetaminophen-poisoned animals were kept normothermic, the preventive effects were abolished. These findings suggest that this protective effect may be mediated by the trifluoperazine blockade of the deleterious effects of calcium accumulation in liver or the trifluoperazine decreasing effects on body temperature. PMID- 2255663 TI - Increased serum selenium levels in patients under corticosteroid treatment. AB - The normal serum and tissue levels of many micronutrients are remarkably affected by the therapeutical administration of several substances. In the present study, we have evaluated the modifications of serum selenium levels in different groups of patients under corticosteroid treatment. Such therapy was significantly associated with increased serum selenium levels, with a dose-dependent relationship in subjects treated with methylprednisolone. The reasons for this association are unknown. However, a reduced renal excretion of selenium, due to the mineralcorticoid activity of the corticosteroids, can be inferred. PMID- 2255664 TI - An automated method for the determination of nortriptyline and its isomeric 10 hydroxylated metabolites in plasma by high pressure liquid chromatography. AB - A high pressure liquid chromatography assay for determination of the tricyclic antidepressant nortriptyline (NT) and its two major metabolites, Z- and E-10 Hydroxy-NT, in plasma is described. Sample preparation included addition of internal standard and a single step extraction procedure. Run time was approximately 14 min. with a LC-18. 5 mu 250 x 4.6 mm column, a mobile phase consisting of aqueous ammonium: methanol: acetonitrile (0.8:6.2:93, v/v), and flow of 1.3 ml/min. NT, Z- and E-10-OH-NT, amitriptyline, Z- and E-10-OH-AT and the internal standard desipramine, were adequately separated within this time span. In our laboratory, the assay has been employed mainly for pharmacokinetic and toxicologic studies in experimental animals at relatively high concentrations. PMID- 2255665 TI - Effects of age and antiepileptic drugs on plasma levels and kinetics of clobazam and N-desmethylclobazam. AB - The authors monitored the plasma levels of clobazam (CLO) and its principal metabolite, N-desmethylclobazam (NCLO) during chronic treatment of more than 400 epileptic patients receiving different co-medications, such as phenytoin (PH), carbamazepine (CBZ), sodium valproate (VPA) and phenobarbital (PB). This study investigated the influence of age and antiepileptic drugs on plasma levels of CLO and NCLO. Plasma concentrations measured 3 hr after morning administration of CLO varied from 30 to 700 [formula; see text] for CLO, and from 160 to 7000 [formula; see text] for NCLO. Plasma levels of CLO were higher in patients aged 20-30 years. NCLO concentrations increased with age up to 20 years. Coadministered antiepileptic compounds significantly decreased maximal plasma levels of CLO. Moreover, PH and CBZ a significantly increased the plasma levels of NCLO. Results on the influence of CBZ on CLO kinetics were confirmed in a group of ten patients receiving PB and VPA and later PB, VPA and CBZ as CLO associated drugs. The influence of VPA on the pharmacokinetics parameters of CLO was also evaluated in a patient in the latter group. PMID- 2255666 TI - Influence of temperature and extracellular pH on contractile responses in isolated human hand veins. AB - The effects of moderate cooling and extracellular pH changes on concentration response relationships for noradrenaline (NA), 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2 alpha) were investigated in isolated human hand veins. pH changes were achieved by altering the NaHCO3 content of the Krebs solution. Cooling to 24 degrees reduced the maximum contractile responses to K+ (124 mM), NA and PGF2 alpha by 20-30%, whereas that to 5-HT was unchanged. The NA and 5-HT potencies were increased 8-10 times, whereas the PGF2 alpha potency was unaffected. A shift from alkalotic (pH 7.6) to acidotic (pH 6.9) conditions did not influence the contractile response to 124 mM K+, whereas the responses to NA, 5-HT and PGF2 alpha were inhibited with regard to both potency and maximum contraction. When related to neutral pH, acidosis significantly reduced only the 5-HT potency (4 times), whereas alkalosis selectively increased the NA and PGF2 alpha potencies (3 times). In the presence of prazosin (10(-7) M) cooling to 24 degrees significantly increased the NA potency, whereas no such increase was seen in the presence of rauwolscine (10(-7) M). Alkalosis significantly increased the NA potency in the presence of either antagonist. In conclusion, temperature and extracellular pH influenced the contractile responses to NA, 5-HT and PGF2 alpha in a differentiated manner. Alkalosis appeared to increase the response to both alpha 1- and alpha 2-adrenoceptor stimulation, whereas cooling preferentially increased that to alpha 2-adrenoceptor stimulation. PMID- 2255667 TI - Effect of cyclosporin A and different vehicles on ATP production in mitochondria isolated from the rat kidney cortex. AB - Isolated rat kidney mitochondria were exposed in vitro to cyclosporin A and three different vehicles, ethanol, DMSO and cremophor. Spontaneous ATP production and oxidative phosphorylation were measured with a bioluminometric method. Both ethanol and cremophor caused a slight (4-7%) decrease in spontaneous ATP production, and also cyclosporin A itself had a minimal effect. On the other hand DMSO had an opposite effect, causing an increase of about 20%. Cyclosporin A showed a dose dependent inhibition of oxidative phosphorylation, being most pronounced when dissolved in ethanol. Cremophor, the castor oil used in commercial preparations caused per se almost a 40% inhibition of the oxidative phosphorylation. PMID- 2255668 TI - Pathophysiologic effects of anatoxin-a(s) in anaesthetized rats: the influence of atropine and artificial respiration. AB - The pathophysiologic effects of anatoxin-a(s) from the cyanobacterium Anabaena flos-aquae NRC-525-17 were investigated in anaesthetized adult male Sprague Dawley rats given the toxin by continuous intravenous infusion until death. Rats (n = 6) pretreated with atropine sulfate (50 mg/kg) intraperitoneally survived significantly longer (P less than 0.05) than non-atropinized rats (n = 6), suggesting that the muscarinic effects of anatoxin-a(s) were important in the lethal syndrome. In contrast to rats only given toxin, rats that were pretreated with atropine had a decrease in heart rate and mean blood pressure that followed profound reductions in respiratory tidal and minute volume, suggesting that neuromuscular blockade of the muscles of respiration was the cause of death. Even when survival time of rats was increased by pretreatment with atropine, phrenic nerve amplitude increased, indicating a lack of a depressive effect of anatoxin a(s) on central mediation of respiration. Rats (n = 3) continuously ventilated during toxin infusion survived a dose more than 4 fold greater than a consistently lethal dose of the toxin. Thus, the cardiovascular effects of anatoxin-a(s) alone could not account for the death of rats. Electromyographic activity recorded from the diaphragms of rats (n = 5) during continuous toxin administration revealed an increase in muscular electrical activity that became more random and finally decreased prior to death, suggesting a toxin-induced neuromuscular blockade in vivo which ultimately was the cause of death of the anatoxin-a(s) dosed rats. PMID- 2255669 TI - Lack of effect of pinacidil on theophylline pharmacokinetics and metabolism in man. AB - Pinacidil, a pyridyl cyanoguanidine derivative, is a new antihypertensive vasodilator drug. It shares structural similarities with the histamine H2 receptor blocker cimetidine, an imidazole cyanoguanidine derivative, which is a potent inhibitor of cytochrome P-450 and of theophylline metabolism. In the present study the pharmacokinetics and metabolism of theophylline were determined in six healthy volunteers before and on the last day of oral pinacidil administration for two weeks. The dosage of pinacidil was 12.5 mg twice a day in the first week and 25 mg in the second. There were no significant changes in theophylline plasma clearance, terminal half-life or volume of distribution during pinacidil administration. Also the renal and metabolic clearance of theophylline and the formation clearances of the major theophylline metabolites in the urine (DMU, 1MU, 3MX) did not change significantly during administration of therapeutic doses of pinacidil. PMID- 2255671 TI - Fluorescent proteins formed in peroxidized microsomes of rat liver. PMID- 2255670 TI - The effects of vadocaine, dextromethorphan, diphenhydramine and hydroxyzine on the ciliary beat frequency in rats in vitro. AB - Mucociliary function is a major cleansing mechanism of the respiratory tract. Many drugs used in the treatment of respiratory diseases impair the ciliary beat frequency (CBF) of mucous membrane. Our aim was to study by means of a photoelectric technique, the effects of two antitussives--dextromethorphan and vadocaine--and two antihistamines--hydroxyzine and diphenhydramine--on the rat tracheal CBF in vitro. The CBF was measured from tracheal explants immersed in drug solutions. Dextromethorphan (1.0 mg/ml and 10.0 mg/ml) caused 16.9-20.8% decrease in the CBF during the 40 min. measurement period. Vadocaine (0.1 mg/ml and 0.5 mg/ml) decreased the CBF by 6.9%. Higher vadocaine concentrations caused a dose-dependent inhibitory effect so that mucociliary function stopped totally within 20 min. with 5.0 mg/ml vadocaine solution. Both diphenhydramine and hydroxyzine totally stopped the ciliary activity during 20 min. with concentrations of 2.5 mg/ml and 1.0 mg/ml. respectively. Locke-Ringer solution used as a control did not cause any change in the CBF. These results suggest that the antihistamines diphenhydramine and hydroxyzine are more ciliostatic than the antitussives dextromethorphan and vadocaine on the rat tracheal cilia in vitro. The results suggest further in vivo studies. The used photoelectric detection method proved to be suitable for evaluating drug effects on the CBF of respiratory mucosa. PMID- 2255673 TI - Increased eggshell thickness in domestic fowls after administration of the antiprogesterone RU 38486 (Mifepristone). PMID- 2255672 TI - Effects of potassium channel openers on pentylenetetrazole-induced seizures in mice. PMID- 2255674 TI - Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphology. AB - This study explored some toxicological aspects of vanadyl sulphate (VOSO4) treatment of rats made diabetic with a single intravenous injection of streptozotocin (60 mg/kg). Administered in drinking water (0.25, 0.5, 0.75 or 1 mg of VOSO4, 5H2O ml) VOSO4 treatment partially or totally corrected some of the alterations associated with the diabetic state (hyperglycaemia, polydipsia, polyphagia, high cholesterol and triglycerides levels) and did not produce any changes in various plasma or blood cell parameters which were not previously altered by diabetes. Measurement of vanadium levels indicated that tissues accumulated vanadium in the following order of concentrations: bone greater than kidney greater than spleen greater than liver greater than lung greater than or equal to muscle greater than blood. Histopathological studies did not reveal any difference in liver, stomach, ileum, spleen, heart and lung from control, non treated diabetic or VOSO4-treated diabetic animals. Kidney of all non-treated diabetic animals showed an epithelial cellular swelling of distal tubules while only 2 of 6 VOSO4-treated diabetic animals showed this alteration. Cellular degeneration of pancreas B-cells was less marked in VOSO4-treated that in non treated diabetic animals. The study indicates that VOSO4 may be a potential antidiabetic agent. PMID- 2255675 TI - Cardiovascular effects of irindalone, a new S2-serotonergic antagonist, in the rat. AB - Irindalone is a new antihypertensive agent with affinity to serotonin (5-HT2) receptors and at higher concentrations also to alpha 1-adrenoceptors. The present study was designed to evaluate the relative importance of the antagonism of central and peripheral alpha 1- and 5-HT2-receptors in the blood pressure lowering properties or irindalone after acute administration. In conscious Sprague-Dawley rats intravenous irindalone (0.05-1.5 mg/kg) dose-dependently reduced the blood pressure. In the same dose-range irindalone antagonized pressor responses to phenylephrine and electrical stimulation of the spinal sympathetic outflow (SNS) in the pithed rats, indicating that the acute blood pressure lowering effect is primarily related to the blockade of alpha 1-adrenoceptors. However, the concomitant 5-HT2-receptor blockade may contribute since irindalone in a dose (0.15 mg/kg) where it had no alpha-adrenoceptor blocking properties enhanced the hypotensive response to selective alpha 1-adrenoceptor blockade by prazosin (1 micrograms/kg). We found no evidence that central mechanisms contributed to the blood pressure lowering effect of irindalone. In anaesthetized rats irindalone (1 mg/kg) did not reduce the directly recorded sympathetic nerve activity. Intracerebroventricular administration of irindalone in conscious rats (10-100 micrograms) had no consistent effects on the blood pressure and did not enhance the hypotensive response to intracerebroventricularly administered prazosin (10 micrograms). Finally, the hypotensive response to irindalone was not influenced by depletion of central serotonin stores (by PCPA). It is concluded that the blood pressure lowering effect of irindalone following acute administration is related primarily to blockade of peripheral alpha-adrenoceptors but that the concomitant blockade of 5-HT2-receptors may contribute. PMID- 2255676 TI - Cortical cerebral blood flow is enhanced by hornet venom. AB - This study examined the effect of Oriental hornet venom sac extract (VSE) on the rate of local blood flow in the cerebral cortex of rats. Sublethal doses of VSE in isotonic saline solution were injected into the femoral vein of anaesthetised rats and the rate of blood flow was assessed by the hydrogen clearance technique both before the envenomation as well as during the following 150 min. The injection of VSE was found to induce a prolonged elevation of blood flow in the cerebral cortex. The time of occurrence of this elevation varied in different rats and so also the intensity of the elevation, ranging between 47-212% of the basal values. No exceptional or toxic phenomena were recorded in the course of this investigation. It would seem that the factor(s) responsible for boosting the blood flow is probably one or more of the water soluble components of the hornet venom. PMID- 2255677 TI - Hydroxyurea: relationship between toxicity and centrally-induced adrenal activation. AB - The anticancer drug hydroxyurea (HU) at doses of 300-800 mg/kg/day causes a dramatic lethality (up to 100% after a 5-day treatment) in hypophysectomized as well as in adrenalectomized rats drinking physiological saline + 5% glucose. Mortality in controls was less than 10% over a 5-day period. Adrenal stimulatory or replacement therapies protect pituitary- or adrenal-ablated rats against HU toxicity. They also counteract white blood cell changes induced by the drug. HU (30-800 mg/kg) induces a dose-dependent increase of plasma corticosterone in normal rats after single or repeated treatments that is not observed in hypophysectomized animals. HU also increases plasma levels of epinephrine, although this finding cannot account for the rise in plasma corticosterone; indeed, it is secondary to a strong rise in plasma corticosterone. The stimulation of the hypothalamic-hypophyseal-adrenal axis induced by HU is responsible for the drug-induced adrenocortical activation. This activation appears to be a valuable defence mechanism protecting intact rats against HU lethality, and its failure causes the dramatic HU lethality in pituitary- or adrenal-ablated animals. PMID- 2255678 TI - Effects of pinacidil upon penile erectile tissue, in vitro and in vivo. AB - The effect of pinacidil, a new antihypertensive vasodilator, was studied in vitro upon human and porcine Corpus cavernosum and in vivo upon simian Corpus cavernosum. In vitro, pinacidil incubation (10(-5)-10(-3) M) was found to induce a concentration-dependent inhibition of the tissue response to norepinephrine (NE) and high potassium (K+). Likewise a concentration-related relaxation of the tissue, precontracted with either NE or K+, was seen using pinacidil 10(-5)-10( 3) M. Depending on the concentration applied, spontaneous activity as well as tone and amplitude of the contractions were reduced until total relaxation of the tissue was obtained with a pinacidil incubation of 10(-3) M. In vivo, 5 mg pinacidil in 0.3 ml solution was injected intracavernosally in 17 monkeys. Sixteen monkeys developed tumescence and 10, rigidity of the penis as well. Only one of 5 showed a decrease in the systemic blood pressure. Pinacidil might be of clinical interest as an agent facilitating erection when given intravernosally. PMID- 2255679 TI - Comparison of the effects of auranofin, heavy metals and retinoids on protein kinase C in vitro and on a protein kinase C mediated response in macrophages. AB - The effect of auranofin (AF), retinoic acid (RA), and three heavy metals reacting with thiol groups (Hg, Cd, Pb) has been compared on a PKC mediated response of intact macrophages (i.e. plasminogen activator (PA) induction) and on purified PKC activity. AF, cadmium chloride, and lead nitrate directly inhibit PKC and hence prevent the induction of PA activity in macrophages stimulated with PMA. In vitro, and in absence of chelators, mercuric chloride is also a potent inhibitor of PKC. However, at the cellular level, the PKC mediated response (PA induction) was not inhibited by non-cytotoxic concentrations of mercury possibly due to interference of the metal with additional cellular mechanisms such as calcium mobilisation. Direct inhibition of PKC is probably not the mechanism by which retinoids block the activation of macrophages. PMID- 2255680 TI - Pharmacokinetics of trimeprazine in children. AB - The pharmacokinetics of trimeprazine (alimemazine) were studied over 24 hr in six children after a recommended preanaesthetic oral dose of 3 mg.kg-1. The degree of sedation before anaesthesia was evaluated. Median maximal venous blood drug concentration was 0.357 mumols.1(-1), 1-2 hr after oral ingestion, half-life 6.8 hr and AUC0-infinity h 2.758 mumols.1(-1) hr. Assuming 100 per cent bioavailability, blood clearance was estimated to median 3.7 1.kg-1.hr-1. Trimeprazine concentrations in cerebrospinal fluid (CSF) and in venous blood were compared in three other children, measured by gas chromatography. No trimeprazine was detected in the cerebrospinal fluid. We found a rough correlation between preanaesthetic sedation and blood trimeprazine concentrations. The kinetic parameters showed substantial interindividual differences, and accordingly, major interindividual variations in drug response might be anticipated even on standardized dosage regimens. PMID- 2255681 TI - Fate of ethion in goats after intravenous, oral and dermal administration. AB - Toxicokinetic parameters and cumulative excretion were studied in goats after intravenous, oral and dermal administration of unlabelled and 14C-ethion. Plasma concentration-time data was subjected to non-compartmental analysis. IV injection studies showed an effective half-life (t1/2) of 2 hr, a total body clearance (ClT) of 3.21.kg-1.hr-1 and a volume of distribution (Vd(ss) of 9.4 1.kg-1. Plasma levels of 14C-ethion (ethion + metabolites) were much higher and more persistent than those of unchanged ethion. Cumulative excretion of 14C-ethion was 78% of the dose with 66% in urine, 8% in faeces and 4% in milk. Oral administration resulted in low plasma levels of unchanged ethion, an absorption half-life (t1/2 abs) of 10 hr and a bioavailability of less than 5%. Cumulative excretion was 80% of the dose with 64% in urine, 14% in faeces and 1.7% in milk. Dermal application showed a t1/2 abs of 85 hr and a bioavailability of 20%. Only 0.05% of the dose was excreted unchanged in milk. It is concluded that (1) orally administered ethion is extensively metabolized in the GIT, (2) dermal application results in prolonged and limited absorption and (3) absorbed ethion is rapidly eliminated through metabolism. PMID- 2255682 TI - Differential relaxant responses to pinacidil of smooth muscle preparations contracted by a high concentration of potassium in isoosmolar and hyperosmolar solutions. AB - Contractions were produced in guinea-pig trachealis, aorta and pulmonary artery by depolarization with 124 mM K+ using two commonly applied techniques. Addition of KCl to the organ bath solution making it hyperosmolar induced slowly developing contractions, which were only weakly inhibited by pinacidil. Hyperosmolar mannitol-induced contractions showed similar characteristics. In contrast, contractions elicited by isoosmolar K+ Krebs solution developed more rapidly and could be completely suppressed by pinacidil (10(-6)-10(-3) M) in a concentration-dependent manner. The findings explain previously published discrepant results on the relaxant response to pinacidil of smooth muscle preparations contracted by high concentrations of K+, and indicate other mechanisms of action for pinacidil in addition to K+ channel opening, in the concentration range 10(-6)-10(-3) M. PMID- 2255683 TI - Immunologic protection against VX intoxication in experimental animals. AB - Rabbits immunized with an artificial VX-antigen could survive 1 x LD95 of VX challenge on the 7th day and the 31st day after the last immunization. One hundred microliters of rabbit anti-VX antiserum given intravenously immediately before 1 x LD95 of VX or 200 microliters of antiserum intraperitoneally 1-10 days before 1 x LD95 VX protected all the tested mice from death. The antiserum could prevent the in vitro inhibition of Torpedo AChE activity by VX and reduced its effect on brain AChE activity in vivo. No protective effect of the antiserum was observed on the Torpedo AChE activity inhibited by sarin and soman. PMID- 2255684 TI - Changes in rat brain monoamines, monoamine metabolites and histamine after a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AB - Male Long-Evans rats were given 50 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) intraperitoneally and after 1, 4, 28 or 76 hr, noradrenaline, dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5 hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan and histamine were measured in the brain (dissected into ten parts) as well as in the pituitary gland. Several slight but significant changes were observed, e.g. in the hypothalamus where HVA and 5-HIAA were decreased after 4 hr, noradrenaline was decreased after 76 hr and histamine increased after 28 hr. Several late changes were also found, conspicuously tryptophan was increased in most brain areas after 76 hr and in some cases earlier; these changes may be due to starvation after hypophagia rather than TCDD directly. The results demonstrate that TCDD causes changes in brain neurotransmitter systems, but the changes are minor and it is not likely that aminergic systems are the key mediators in TCDD induced hypophagia. PMID- 2255685 TI - Attenuated endothelium-dependent rat aortic relaxation following inhibition of nitric oxide formation from L-arginine. PMID- 2255686 TI - Reduction of eggshell thickness by a proton pump inhibitor, omeprazole. PMID- 2255687 TI - [Thermal indicator diagnosis of lung pathology at a rural hospital]. AB - Findings of liquid crystalline thermography used for the diagnosis of lung pathology at a rural hospital during 1984-89 are summarized. The above method helps to select those from the rural population who suffer from lung pathology and to organize their timely examination and treatment. As compared to the previous years, average increase in the number of out-patients examined at a regional antituberculosis institution made up 23.7% over the given period. At the present stage of rural health care development, express diagnosis of lung pathology promotes the integration of phthisiology and pneumology services, which greatly improves the system of medical examination of the rural population. PMID- 2255688 TI - [A system of comprehensive screening for tuberculosis and other chronic diseases of the respiratory organs in a rural area]. AB - Pulmonary disease screening system, including fluorography, interview and external respiration function tests was used in 6 regions of this country. Out of 90,262 people examined, 23,360 persons were subjected to external respiration function test. As a result of the screening, the following conditions were detected: active tuberculosis in 0.02-0.8%, lung cancer in 0.02-0.3%, X-ray positive and X-ray negative chronic non-specific bronchopulmonary diseases in 0.12-3.7% and 7.7-15.2% of these cases, respectively. PMID- 2255689 TI - [Pulmonary tuberculosis as detected by different methods]. AB - As a result of the study of clinico-roentgenologic pictures of 379 patients with newly-diagnosed pulmonary tuberculosis, asymptomatic and undetectable development of the disease was found in 64.2% of the cases with non-destructive and in 35.0% with destructive processes. Besides, clinical symptoms of 36.1% of the patients were neglected. The above situation proves it necessary to conduct preventive fluorographic examinations of the chest at least once every 2 years. Their quality should be significantly improved, as many patients had fluorographic changes on the prior examination, which were missed or misinterpreted. The organization of early tuberculosis detection cannot be judged from the proportion of destructive processes in the pattern of tuberculosis morbidity. PMID- 2255690 TI - [Clinico-morphologic and echographic comparisons during the study of the liver in patients with pulmonary tuberculosis and diabetes mellitus]. AB - A comparative clinico-morphologic and echographic study of the liver in 50 patients with pulmonary tuberculosis and diabetes mellitus was conducted. Comprehensive examination confirmed the following conditions: chronic active hepatitis in 3; chronic persistent hepatitis in 8; non-specific reactive hepatitis in 4; liver cirrhosis in 3; fatty degeneration in 10; and fibrosis of the liver in 22 patients. Ultrasonic examination made it possible to observe the most evident changes in chronic active hepatitis, liver cirrhosis and fatty degeneration, while less evident changes were seen in chronic persistent hepatitis, non-specific reactive hepatitis and fibrosis of the liver. Thus, an ultrasonic examination reflecting a certain morphologic restructuring of the organ may render a great help in detecting different forms of the liver lesions. PMID- 2255691 TI - [Early results of the treatment of patients with recurrences of pulmonary tuberculosis]. AB - Efficacy of treatment of 106 patients with destructive forms of recurring pulmonary tuberculosis is analysed. Treatment was conducted in comparable groups on 2 chemotherapeutic regimens. With regimen 1 consisting of a 4-drug combination, cavity closure was evident in 72.2%, while with regimen 2 including 3 drugs, cavities were closed in 42.3% of the cases. Cavity decay healing and bacteriostasis rates were higher for regimen 1 as compared to regimen 2, though the incidence of bacteriostasis was the same with both chemotherapeutic regimens, i.e. in 93.6% and in 92.8% with regimen 1 and 2, respectively. The incidence of side effects was practically unchanged in terms of the given chemotherapeutic regimen. A 4-drug combination should be chosen for the management of patients with destructive recurring pulmonary tuberculosis. PMID- 2255692 TI - [The possibilities of shortening the treatment periods in patients with tuberculosis of the peripheral lymph nodes]. AB - Outcomes of shorter periods of treatment of patients with tuberculosis of the peripheral lymph nodes are presented. It is possible to reduce the period of treatment provided early surgical intervention is performed to remove the affected nodes. One recurring case detected after the long-term therapy. The counterindications for reduction of treatment periods of the above disease are generalization of the process and Mycobacterium resistance to tuberculostatic drugs. PMID- 2255693 TI - [The use of apressin in patients with pulmonary tuberculosis and functional disorders of the external respiration and hemodynamics]. AB - Effects of apressin, a peripheral vasodilator, on external respiration function and central hemodynamics was studied in 51 patients with pulmonary tuberculosis. The study showed that a single administration of 20 mg apressin in pulmonary tuberculosis patients failed to bring about any changes in both external respiration function and blood gases, only causing a minor shift in the buffer bases. Systolic pressure in the pulmonary artery remained unchanged after a single 20 mg dose of apressin was given. A statistically significant decrease in total pulmonary vascular resistance and an increase of the central hemodynamic values in pulmonary tuberculosis patients with hypokinetic type of circulation are recorded. PMID- 2255695 TI - [The prognosis of disorders of gas exchange and hemodynamics in the early period following pneumonectomy]. AB - The study demonstrated that patients having the baseline low arterial blood oxygen tension and high bronchial resistance showed the most unfavorable changes in the main integral values of gas exchange and hemodynamics on day 4 after pneumonectomy. Considerable progression of the obstructive syndrome, aggravation of arterial hypoxemia, significant rise of arterio-pulmonary blood pressure and perceptible drop of cardiac motor function are observed in these cases. The data may be used to predict gas exchange and hemodynamic disturbances in the early period after pneumonectomy. PMID- 2255694 TI - [The use of rheography for assessing the adequacy of prolonged artificial ventilation of the lungs in patients undergoing surgery of pulmonary tuberculosis]. AB - When prolonged end-expired-air positive pressure ventilation (EEPPV) is performed to prevent possible respiratory complications after operation for pulmonary tuberculosis, thorough monitoring of the circulation system seems to be necessary since EEPPV affects the cardiovascular system. In this case rheography makes it possible to objectively assess the hemodynamics and phasic pattern of heart performance. An optimum regimen of EEPPV is that which ensures a maximum increase of the pulmonary ventilation in each zone, including the best blood oxygenation without negative action of EEPPV on circulation. EEPPV below 10 sm H2O is recommended for patients with disseminated and complicated tuberculosis. PMID- 2255696 TI - [Variants of an unfavorable course of sarcoidosis and its differential diagnosis]. AB - The following 3 forms of an unfavorable course of sarcoidosis were identified and described: 1) infiltrative-and-pneumonic; 2) that taking the course of fibrotic alveolitis; and 3) generalized sarcoidosis with hepatolienal syndrome. Clinical and X-ray pictures of these forms together with therapeutic results and outcomes are given. PMID- 2255697 TI - [Clinical criteria of the early diagnosis of status asthmaticus and its treatment]. PMID- 2255698 TI - [The efficacy of treating pulmonary tuberculosis with amniocene]. PMID- 2255699 TI - [Immunologic indices of the blood and synovial fluid before and after subcutaneous administration of tuberculin in patients with osteoarticular tuberculosis]. AB - The contents of immunoglobulins, T-lymphocytes, immune rosette-forming cells and indirect hemagglutination test titer in serum and in synovial fluid before and after subcutaneous tuberculin were found in 44 patients with locomotor diseases of different etiology. A comparative assessment of immunologic indices in different groups of patients made in possible to substantiate diagnostic criteria surgical tuberculosis. PMID- 2255700 TI - [Bronchoscopic data in patients with residual post-tubercular changes and their role in determining the reactivation of respiratory tuberculosis]. PMID- 2255701 TI - [Lesions of the serous membranes in adults with tuberculosis]. PMID- 2255702 TI - [Lymphosarcoma with disseminated lesions of the lungs and peripheral lymph nodes]. PMID- 2255703 TI - [Dynamics of the activity of antioxidant enzymes in the blood of patients with pulmonary tuberculosis]. AB - The given article deals with the results of analysing antioxidative enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) in the blood of pulmonary tuberculosis patients. It is demonstrated that with focal tuberculosis, lipid peroxidation rises, compensatory increase in SOD, GP and GR levels takes place. In infiltrative and disseminated tuberculosis, multidirectional changes of SOD, GP and GR levels are observed depending on a certain stage of the disease accompanied by an increased lipid peroxidation. PMID- 2255704 TI - [A method of differentiating transudate and exudate]. AB - A diagnostic value of pleural fluid alkaline phosphatase (AP) for transudate and exudate differentiation is shown. AP below and above 0.5 mumol/(ml.h) are characteristic of transudate and exudate, respectively. PMID- 2255705 TI - [Morphological changes in the liver of patients with pulmonary tuberculosis- carriers of hepatitis B virus]. AB - Findings of morphologic studies of the liver bioptic material taken from 42 patients with different forms of pulmonary tuberculosis, hosts of Hbs-antigen, are described. It appears that marked dystrophic, inflammatory and necrotic changes occur in patients of this category, which should be taken into account when etiotropic and pathogenetic therapy is chosen. PMID- 2255706 TI - [Determination of the status of central hemodynamics using the method of tetrapolar thoracic rheography]. PMID- 2255707 TI - [Psychological characteristics of patients with tuberculosis]. PMID- 2255708 TI - [The pro-fibrotic and pro-oxidant action of isoniazid]. AB - As a result of experimental research on rats with destructive pulmonary tuberculosis, oxidative action of isoniazid in a dose of 50 mg per kg body weight, corresponding to the mean therapeutic dose of 10 mg/kg in man, was clearly defined. Fibrotic action of the drug was also shown. It manifested itself by a sharp rise of insoluble collagen levels in the lung tissue tuberculous lesion focus of the treated animals and in the formation of mature connective tissue. Two mechanisms of isoniazid's pro-fibrotic action are presented. PMID- 2255709 TI - [Myxedematous accumulation of fluid in the pleural cavity of a female patient with the Van Wyk-Ross-Hennes syndrome]. PMID- 2255710 TI - [Drug allergy originating in Goodpasture's syndrome]. PMID- 2255711 TI - Can a nurse be a therapist? Running an anxiety management group. AB - Anxiety can have as debilitating an effect as illness. A nurse at a day hospital took control of an anxiety management group, helping clients to manage and control their anxiety. Should nurses undertake this role more widely in the future? PMID- 2255712 TI - So you think you need a computer? AB - Nurses undertaking research projects, a degree or diploma will find a computer an invaluable addition to their lives. However, the bewildering range of products and the complexity of design can be daunting for first time buyers. This article summarises those computers best suited to your needs. PMID- 2255713 TI - A patient's eye view. PMID- 2255714 TI - An acknowledgement from outside. PMID- 2255715 TI - A chance for nursing to lead the way. PMID- 2255716 TI - An open approach to minimise the effect. Sexuality and renal patients. AB - Chronic illness can have a significant effect on sexuality. Nurses caring for people with renal failure must recognise this and be prepared to discuss sexuality sensitively and openly, referring problems to a sex therapist if necessary. PMID- 2255717 TI - What is premenstrual syndrome? Help and support for women with PMS. AB - Most women experience the anxiety, restlessness and irritability associated with premenstrual syndrome at some point in their lives. The syndrome should, however, be explained in clinical terms, its aetiology defined and treatment offered. PMID- 2255718 TI - Asthma: meeting the demand for rapid relief. Drugs and inhalation devices. PMID- 2255719 TI - A systematic approach to trauma relief. The management of the A&E wound. AB - Nurses working in A&E departments are faced with a variety of wounds and an ever increasing choice of dressings. It is vital, therefore, that they maintain an up to-date awareness of the developments in wound care. PMID- 2255720 TI - A superior method of tube placement. Percutaneous endoscopic gastrostomy. PMID- 2255721 TI - A preventable course of infection. Carriage of gram-negative bacilli on hands. AB - Research shows nurses do not pay enough attention to handwashing techniques, and the results of a study on the carriage of gram-negative bacilli reveal an alarming contamination rate. PMID- 2255722 TI - Effects of a single inescapable swim on long-term brain stimulation reward thresholds. AB - Rats were subjected to a 15-min inescapable swim in a procedure which induces "behavioral despair" (immobility) 24 hr later. Their thresholds for brain stimulation reward were measured six times over the subsequent two weeks. Under one condition thresholds were first determined 3 hr postswim and, under a second condition, 24 hr postswim. Rats tested in the 3-hr condition showed elevated thresholds compared to preswim baselines. Elevations remained significant for six days. Thresholds for rats in the 24-hr condition did not change. Results are discussed in terms of a) the lack of correspondence between behavioral despair and brain stimulation reward models of depression, b) possible mechanisms for the 3-hr condition effect, and c) the significance of long-term changes in brain reward substrates. PMID- 2255723 TI - The effects of intermittent dietary restriction on weight gain and body fat in white-footed mice, Peromyscus leucopus. AB - The effects of repeated food restriction-refeeding cycles were investigated in second generation captive Peromyscus leucopus. Mice were maintained on 50% of their individual predetermined ad lib diet for 5 days followed by 10 days of refeeding ad lib. Cycles were repeated 3 times. When compared with controls maintained ad lib for the same time period, no significant differences in final weight or fat content were observed. Restricted-refed mice were, however, observed to both lose and regain weight at increasing rates with each subsequent cycle. PMID- 2255724 TI - New paradigms for tactile discrimination studies with the rat: methods for simple, conditional, and configural discriminations. AB - This paper describes a number of new tactile discrimination tasks for rats. Rats that were placed on a small platform were trained to pull up strings to obtain attached food pellets. When presented with two different sized strings, the rats acquired size discriminations and reversals within 5 to 10 days. When differences between string sizes were varied, the rats could discriminate differences less than one millimeter. A conditional task, in which the location of the correct string was made contingent on string size, was acquired within about forty days. A configural task, in which a compound of string size and odor predicted reinforcement, was acquired within about fifty days. The task is easy to use, provides good contiguity between specified cues and reinforcement, and can be easily modified to study a variety of within modality and cross modality sensory problems. Since the task can be adapted for simple associative, conditional, and configural problems it could prove useful for studying neurobiological substrates underlying learning and memory, cross modal matching, and recovery of function. PMID- 2255725 TI - A possible alarm substance in the forced swimming test. AB - Rats were tested in a forced swimming paradigm under a number of conditions which showed that time of day of testing did not significantly affect duration of immobility and a shorter ten-minute test period was as effective as the traditional longer protocol which tests animals 24 hours after initial immersion. Prior foot shock and noise decreased the immobility response. In addition, swimming in a cylinder in which another rat had been swimming also decreased the immobility response. The latter was not due to fecal or urinary contamination but appeared to be due to an alarm substance released during immersion in the water. Animals were affected by this proposed substance whether they released it themselves or it was released by a stranger. The proposed substance was released after a 3.5-minute or longer swimming period. PMID- 2255726 TI - Oral administration of proteinase inhibitor II from potatoes reduces energy intake in man. AB - The effect of a proteinase inhibitor extracted from potatoes (POT II) which increases CCK release, on food intake was examined in 11 lean subjects. They received 1.5 g POT II in a high-protein soup vehicle (70 kcal), the soup vehicle alone, or a no-soup control five minutes before being presented with a lunchtime test meal, according to a double-blind, within-subjects design. Consuming the soup alone led to a nonsignificant 3% reduction in energy intake. The addition of 1.5 g POT II to the soup significantly reduced energy intake by a further 17.5%. Premeal ratings of motivation to eat and food preferences did not predict the reduction in energy intake by the proteinase inhibitor. These findings suggest that endogenous CCK may be important in the control of food intake and that proteinase inhibition may have therapeutic potential for reducing food intake. PMID- 2255727 TI - Hepatic metabolism of meal-fed rats: studies in vivo and in the isolated perfused liver. AB - Hepatic metabolic fluxes (glycolysis, glucose release, glycogenolysis, oxygen consumption, ketogenesis and gluconeogenesis), hepatic glycogen and food ingestion in meal-fed rats were measured and compared to appropriate controls. The following results were obtained: 1) in livers from meal-fed rats a higher fraction of glucosyl units derived from glycogen is used in glycolysis instead of being released in the form of glucose; 2) the rate of glycogen catabolism in livers from meal-fed rats is less than expected when one compares their glycogen levels with those of the appropriate controls; 3) the livers from meal-fed rats become much less ketotic than the livers from rats which were not trained to eat a single meal daily. It was concluded that the liver of meal-fed rats is well adapted to the main characteristics of those animals, e.g., increased lipogenesis from glycolysis products and a reduced need for carbon units from the liver (glucose and ketone bodies) as a consequence of enhanced food intake. PMID- 2255728 TI - Circadian rhythms in the short-tailed shrew, Blarina brevicauda. AB - Circadian rhythms of wheel running and feeding were measured in the short-tailed shrew. Shrews were strongly nocturnal, and their activity rhythms entrained to both long-day (LD 16:8) and short-day (LD 6:18) photocycles. Under conditions of continuous light (LL) or darkness (DD), the activity rhythms free-ran with average periodicities of 25.1 hours and 24.1 hours, respectively. In LL the level of activity was depressed, and in some cases wheel running was completely inhibited. No significant sex differences were observed in the period or amplitude of the monitored circadian rhythms. All shrews fed throughout the day and night; however, unlike in previous reports, ultradian periods of feeding behavior were not found. The results are related to Aschoff's four observations for the effect of light on activity rhythms in nocturnal rodents. PMID- 2255729 TI - Locomotor stepping elicited by electrical stimulation of the hypothalamus persists after lesion of descending fibers of passage. AB - Locomotion initiated by electrical stimulation of the lateral hypothalamus could be due to activation of local neurons or of fibers of passage descending from locomotor regions in the basal forebrain. This study mapped hypothalamic sites for electrically elicited locomotion in six rats with electrolytic lesions of the ipsilateral basal forebrain sources of descending fibers of passage. For mapping, anesthetized rats were held in a stereotaxic apparatus supported by a sling so that stepping movements rotated a wheel. Anesthesia was maintained by periodic injections of Nembutal (7 mg/kg) supplemented by lidocaine injections. Stimulation (25 and 50 microA, 50 Hz, 0.5 msec cathodal pulses, 10 sec trains) was applied through 50-80 microns diameter pipettes filled with 2 M saline. In all cases, locomotor stepping could be elicited by stimulation in sites ipsilateral to the lesion at currents of 50 microA or less. In the one case in which 25-microA sites were not found in the lateral hypothalamus, the lesion extended caudally to within 1 mm of the stimulation sites. These findings do not exclude a locomotor role for fibers of passage but they suggest that activation of lateral hypothalamic neurons is sufficient to initiate locomotion. PMID- 2255730 TI - Lever-press conditioning in the crab. AB - An operant chamber has been developed for studying lever-press conditioning in the green crab Carcinus maenas. In one series of experiments, animals were presented with a single bar and were reinforced with food for every bar press. Performance increased over time and high rates of responding were observed after 2 days of training. The response rate was always higher than that for a yoked (noncontingent) control group. When the contingencies were switched, the animals adjusted to the new conditions. Discrimination in the lever-press apparatus was demonstrated in a second experiment in which crabs had to choose between two bars, one (S+) caused food to be dispensed while the other (S-) was inactive. Experimental animals pressed the S+ bar at a significantly higher rate than the S bar. When the contingencies associated with the lever were reversed, animals learned to switch to the correct bar by the second day. It was not necessary to reinforce every response: animals maintained high rates of responding on a schedule where every other response was reinforced. Animals used different methods of pressing the bar; the most common was extension of the claw, predominantly at the meropodite-carpopodite joint. PMID- 2255731 TI - Body weight rhythmicity in the unweaned female rat following neonatal estrogen treatment. AB - Male and female rats were weighted daily throughout this study to determine whether neonatal exposure to estrogens influences body weight (BW) patterns, particularly during the period before weaning when vaginal opening (VO) occurs as a consequence of this treatment. Females receiving estradiol benzoate (EB) at the age of 5 days had greater body weight than their controls soon after the treatment and until day 21. Clear 3-day periodic changes of BW, between days 9 and 20, were revealed by the spectral analysis of the results in EB-given females which did not occur in their controls. Changes of BW (at 4-day intervals) were verified in adult control females whereas age-matched EB-treated females did not show such a rhythm. Neither BW gain nor infradian rhythmicity were detected in infantile males after neonatal EB treatment. The results suggest that, as in spontaneous puberty, a relationship between the occurrence of VO and the establishment of the infradian body rhythmicity in the infantile estrogenized female may exist. PMID- 2255732 TI - Corn oil and mineral oil stimulate sham feeding in rats. AB - To determine the orosensory effects of oils on ingestion, we measured the 1 bottle intake of corn oil and of mineral oil during 30 minutes of sham feeding in rats that were food deprived overnight or nondeprived. Rats sham fed both oils. Food-deprived rats ingested significantly more of both oils than nondeprived rats. Rats discriminated corn oil from mineral oil and as little as 0.78% corn oil emulsion from water. When rats sham fed 8 dilutions of corn oil, intake was an inverted-U function of concentration with maximal intakes produced by 12.5%, 25% and 50% corn oil emulsions. Despite similar, sometimes equal, intakes of corn oil and mineral oil in 1-bottle tests, food-deprived and nondeprived rats showed a strong preference for corn oil in 2-bottle, sham-feeding, preference tests. The sensory mechanisms that mediate the oral effects of oil on intake and preference are not known, but the olfactory and trigeminal sensory systems are the most likely candidates. Further work is required to characterize the potency, sensitivity, and discriminability of the orosensory effects of oils, the mechanisms that mediate them, and their role in the control of fat intake. PMID- 2255733 TI - Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress. AB - The aim of this study was to see whether neonatal handling can reverse the behavioral deficits induced in rats by unpredictable prenatal stress. Rats (24) were exposed to random noise and light stress (RS) on a random basis throughout pregnancy. Half the litters of RS and control (C) dams were subjected to neonatal handling (NH), 3' daily for 21 days. Behavioral measures, open field in both sexes and plus maze test in females only were conducted at 1.5-2 months, and spatial lateralization by amphetamine-induced rotation, in females at 3 months. RS caused significant increases in emotionality and timidity (higher incidence of defecation and less time in open arms of plus maze), and a change in directional bias towards the left. NH completely reversed all these behavioral abnormalities in RS rats but had little effect in C. It is concluded that NH can influence postnatal development of brain organisation in the opposite direction to that induced by prenatal stress. PMID- 2255734 TI - Human daily rhythms measured for one year. AB - Four human subjects recorded their wake-up and to-sleep times for one year each. The data were plotted to display individual circadian rhythms and the data were analyzed statistically. First, individuals had characteristic patterns in which visible changes in the patterns were observed mainly when time zones were changed because of travel. Second, the months with the latest wake-up and latest to-sleep times concentrated around the winter solstice; the months with the earliest wake up and earliest to-sleep times concentrated around the fall equinox. Third, new moon versus full moon days were not different. Fourth, one-hour changes between standard and daylight savings time in the USA were reflected by near one-hour changes in two subjects, but not in a third. Fifth, weekend delays in wake-up time (0.8-1.6 hours), weekend delays in to-sleep time (0.1-0.5 hours), and shorter weekend awake time (0.8-1.3 hours) were observed. Sixth, throughout the year, wake-up times were close to the time of sunrise, but to-sleep times were several hours past sunset. PMID- 2255736 TI - Age-related stimulatory and inhibitory effects of suckling regulate lactation in rabbits. AB - Milk production and the duration of lactation were compared between control rabbits nursing their own pups and those whose litters were replaced by younger, i.e., 4-6 days old, or older pups (20-23 days old) starting at pp days 4, 10 or 15. In rabbits whose pups were exchanged on pp day 4 by older pups, an early decline of milk secretion was induced and similar yields to those of late lactating controls were produced during mid lactation. Conversely, yields similar to those of mid-lactating controls were produced in late-lactating mothers nursing young pups continuously since pp day 10 and high yields were maintained in these animals until pp day 45. When litter exchanges, by either older or younger pups, were delayed until pp day 15, yields were not significantly different from controls. These results indicate that qualitative changes in suckling stimulation develop as the litter grows older, i.e., young pups stimulate milk secretion, whereas old pups inhibit it. Thus, suckling itself may determine the overall pattern of milk secretion in these species. PMID- 2255735 TI - Adrenal morphometry in unilateral and sham adrenalectomized Syracuse high and low avoidance rats. AB - Syracuse high (SHA) and low (SLA) Long-Evans rats, bred for differences in avoidance performance, exhibit dramatic differences in adrenal gland weight. Here we examined adrenal weight and composition (i.e., the size of the medulla, zonae fasciculata/reticularis and glomerulosa) following unilateral adrenalectomy and sham surgery in these strains. Adrenals of SLA animals, regardless of treatment, were heavier and contained larger medullas and cortices than did adrenals of SHA animals. When individual regions were expressed as a percent of total adrenal area, SHA glands (age 31-45 days), although smaller in weight, contained a larger percentage of glomerulosa than did adrenals of SLA animals. Unilateral adrenalectomy produced significant compensatory growth in SHA and SLA animals as indexed by increases in adrenal weight as soon as 7 days after surgery. The adrenal enlargement was the net result of an increase in absolute size of the fasciculata/reticularis (significant 14 days following surgery) and a decrease in the absolute size of glomerulosa (significant 7 days following surgery). These results suggest that SHA and SLA adrenal differences may be the result of genetically determined differential pituitary-adrenal activity. PMID- 2255737 TI - Prolactin and propranolol prevent the suckling-induced inhibition of lactation in rabbits. AB - The normal once-a-day frequency of suckling in the rabbit was increased on day 31 (late lactation) by the addition of two extra sucklings (8 and 16 hr after) the daily suckling. In confirmation of previous data, two additional sucklings significantly decreased milk yield acutely on day 31 in comparison with the average 4-day milk yield before and after day 31. The decrease in milk secretion after the two additional sucklings was prevented by a single injection of 3 mg prolactin (given 24 hr before the two extra sucklings) and/or by injections of the beta-adrenergic-blocking drug, propranolol (100 micrograms/kg b. wt. given 30 min before each additional suckling). Since prolactin secretion is decreased in these species and the mammary gland is less responsive to the hormone during late lactation, the present results suggest that in addition to these factors, suckling-induced activation of sympathetic influences may contribute to the decline in milk production at this stage of lactation. Taken together, these results suggest that suckling may regulate lactation in the rabbit through antagonistic mechanisms at different stages of lactation. PMID- 2255738 TI - Enhancement of nighttime alertness and performance with bright ambient light. AB - Objective levels of alertness and performance efficiency were measured in twenty five healthy young adults during two simulated night shifts. Following the first night shift, during which all subjects worked under dim ambient light (10-20 lux), subjects were assigned to one of three ambient lighting conditions (10-20 lux, 100 lux or 1000 lux) for the second night of work. Subjects exposed to 1000 lux ambient light maintained significantly higher levels of alertness across the 8-hour shift than did subjects exposed to the dimmer lighting conditions. Cognitive performance was also significantly enhanced under the bright light condition, whereas simple reaction time was not. The findings indicate clearly that ambient lighting levels can have a substantial impact on nighttime alertness and performance and that bright ambient illumination may be effective in maintaining optimal levels of alertness during night shift operations. PMID- 2255740 TI - Contribution of spontaneous activity to daily energy expenditure of adult obese and lean Zucker rats. AB - The contribution of somatomotor activity to daily energy expenditure was estimated in 10-month-old, weight-stable, obese (fa/fa) and lean (Fa/?) Zucker rats. Total and resting heat production were assessed by recording oxygen consumption and stabilimeter activity each minute for five consecutive days in free-feeding animals. The number of activity counts, as well as their circadian pattern of occurrence, were highly similar in lean and obese groups. Likewise, the percentage of daily energy expenditure committed by the obese rats to activity was nearly identical to that of leans (19.3 vs. 19.7%, respectively). Observing these rats for one additional day under postabsorptive conditions produced similar estimates of their daily expenditure on activity. Thus, unlike prior estimates based on wheel-running behavior, continuous measurement of stabilimeter behavior indicates that both the proportion of daily expenditure on activity by fa/fa rats and its temporal pattern of occurrence are notably normal. Accordingly, it is concluded that maintenance of obesity in weight-stable adult obese Zucker rats does not depend upon a reduced expenditure on activity. PMID- 2255739 TI - Feeding pattern of liver-transplanted rats. AB - It has been proposed that the liver is involved in the control of food intake (FI). Various studies utilizing hepatic vagotomy have cast doubt on the role of hepatic metabolic receptors. Feeding patterns of male adult Lewis rats were continuously recorded in one group of animals after orthotopic liver transplantation (T), without reestablishing arterial flow. Rats of a second group were dearterialized (D) and had their livers freed from the hepatic pedicle, while rats of a third group were laparotomized (L) and served as sham-operated controls. Meal pattern analyses and body weight (BW) changes were followed after surgery. When T rats began to recover BW, a fourth nonoperated control group (C) was added with BW paired to the T group. From days 15 to 25 the T rats gained significantly less BW than C rats and their 24-hour FI was reduced: daytime FI was augmented while nighttime FI was decreased. Meal number was unchanged. Daytime meal size was increased while nighttime meal size was diminished. Between days 50-60, the BW gain of the T group was nearly identical to that of D or L rats from days 15-25. Data from these two periods were compared. The 24-hour FI was identical, nighttime FI remained significantly lower in T rats. Because of variation in BW recovery of the T rats an additional comparison was made between the T rats after they recovered their BW following surgery, and the D and L rats (days 15-25). All feeding pattern parameters were identical in T, D and L rats. Liver transplantation was followed only by small long-lasting changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255741 TI - A temporally detailed reanalysis of the conditional heart rate response in dog. AB - We used rapid (500 Hz) digital sampling to derive a detailed analysis of the HR conditional response in dog (n = 11) to a 30-sec tone (CS+) followed by a 1/2-sec shock. We found an initial bradycardia at 1.5 +/- 1.0 sec in 6 of 11 dogs from a pre-CS+ control of 85 +/- 26 bpm (mean +/- SD) to 74 +/- 25 bpm (p less than 0.05). In 9 of the 11 dogs there was a subsequent rapid (19.9 +/- 6.7 bpm/sec) increase (+26 +/- 10 bpm) in HR lasting from 1.3 +/- 0.9 to 2.7 +/- 1.0 sec. This was followed by a second, larger (+41 +/- 16, p less than 0.05), but slower (4.0 +/- 2.4 bpm/sec, p less than 0.05) tachycardia which lasted from 4.9 +/- 1.0 to 13.5 +/- 2.6 sec. The peak HR (131 +/- 27 bpm) was attained at 15.0 +/- 3.8 sec, after which HR fell slowly (-2.4 +/- 1.4 bpm/sec) to an average of 92 +/- 29 bpm at 28.6 +/- 1.4 sec (i.e., approximately 1.4 sec prior to shock delivery). This analysis revealed trends in the conditional HR response which were not discernible in individual trials and were obscured in the more traditional analyses of the conditional HR response. PMID- 2255742 TI - Enhancement of electrically elicited startle by amygdaloid stimulation. AB - Previous experiments showed that acoustic startle amplitude can be enhanced by electrical stimulation of the amygdala. Because the acoustic startle pathway is organized in a serial fashion, startle can be elicited electrically with progressively shorter latencies by stimulating different points along this pathway [i.e., ventral cochlear nucleus (VCN), paralemniscal zone (PLZ), nucleus reticularis pontis caudalis (RPC) or medial longitudinal fasciculus (MLF)]. The present study evaluated the temporal characteristics of the facilitatory effect of amygdaloid stimulation on startle elicited electrically from different points along the acoustic startle pathway. A single 0.1-msec pulse was delivered to the central nucleus of the amygdala at various times before the onset of a 1-msec pulse in various sites in the startle pathway. The shortest amygdaloid stimulation-startle onset interval to significantly enhance startle was 0 msec for the VCN, 2 msec for the PLZ, 3 msec for the RPC and 7 msec for the MLF. These results indicate that amygdaloid stimulation enhances electrically elicited startle in a temporal manner that is complementary to facilitation of acoustic startle. The similarity of amygdala-stimulated enhancement and fear potentiation of electrically elicited startle is also discussed. PMID- 2255743 TI - The septum as origin of a lordosis-inhibiting influence in female rats: effect of neural transection. AB - The septum as the origin of a lordosis-inhibiting influence in female rats has been studied. Prior to testing, brain surgery was performed. Some rats were given a ventromedial cut (VMC) just above the anterior commissure, other rats, a posterior transverse cut (PC) or a dorsal horizontal cut (DC) just below the corpus callosum, and still other rats, a bilateral ventrolateral cut (VLC) in the ventrolateral septum and the bed nucleus of the stria terminalis (BST). Additionally, castrated females and those with a VLC sham operation served as castrated controls and sham-operated controls, respectively. All rats were given a daily dose of 0.2 micrograms of estradiol benzoate (EB) for three days and 0.5 mg of progesterone just prior to testing. The castrated controls evidenced no lordotic response. Lordotic activities also were very low in the surgically operated groups, with the exception of the VLC rats who demonstrated significantly high lordotic scores following the administration of 0.2 micrograms of EB. Two further testings, with the EB increased to 0.5 micrograms, were conducted, the interval between these tests being 2 weeks, and the VLC rats again demonstrated significantly higher lordotic activity than did the other rats. These results suggest that the septum exerts a lordosis-inhibiting influence, and that the ventrolateral outputs play a critical role in sending this inhibitory signal. PMID- 2255744 TI - Two-eyed versus one-eyed salamanders: does binocularity enhance the optically evoked skin blanching reactions of Ambystoma larvae? AB - A wide variety of visual functions show increases attributable to binocularity, and the question pursued here was whether a second eye enhances the visually stimulated skin blanching reaction of the larval salamander. Dermal melanin spots (produced by the aggregations of melanosomes within dermal melanophores and which contract or expand to lighten or darken the skin) were measured in eyeless (controls), one-eyed and two-eyed Ambystoma punctatum larvae after chronic adaptation of the subjects to a white background (i.e., stimulus conditions for maximum blanching). The eyeless subjects showed no blanching (thus remained dark) in white cups, and they exhibited melanin spots 7 or 8 times the size of those of the other two groups. All one-eyed or two-eyed subjects exhibited blanching reactions; planometric comparison revealed a significantly larger melanin spot area for one-eyed than for two-eyed animals; i.e., the binocular condition permitted greater contraction of the pigment spots than did the monocular condition. Analytical data compared favorably with independently ascertained pigmentation indices. The results indicate that a second eye quantitatively elevates the blanching maximum of a larval salamander. PMID- 2255745 TI - Variations in chin-marking behavior of New Zealand female rabbits throughout the whole reproductive cycle. AB - Chin-marking (chinning) was measured daily in intact New Zealand female rabbits across their whole reproductive cycle. In Experiment 1 does displayed during estrus (48 days studied) three phases, adaptation, growth and plateau, characterized by progressively higher chinning scores (mean +/- SE = 3.6 +/- 1.1; 17.7 +/- 6.3; 26.6 +/- 4.9 marks/10 min, respectively). Despite great quantitative differences among individuals, these 3 phases and the occurrence of chinning "peaks" at 4-6 day intervals were consistently observed in all subjects (Ss). Mating provoked, within one hour, a dramatic decrease in chinning. Both pregnant and pseudopregnant Ss showed low chinning scores for the first 13 days after mating (combined mean +/- SE = 7.3 +/- 3.8 marks/10 min). From days 14 to 30 postcoitus chinning gradually rose in the pseudopregnant Ss (mean +/- SE = 12.7 +/- 5.4 marks/10 min) while remaining low in the pregnant ones (mean +/- SE = 2.6 +/- 1.9 marks/10 min). Parturition allowed a gradual rise in chinning scores. In Experiment 2 the same Ss were explored across a second reproductive cycle that included lactation. In contrast to Experiment 1, no significant variations in chinning were displayed along estrus, Ss showing high chinning scores already on the first day of observation (mean +/- SE from 12 days = 19.2 +/- 6.7 marks/10 min). In agreement with Experiment 1, mating drastically reduced chinning scores. Low levels were maintained throughout pregnancy (mean +/- SE = 3.4 +/- 2.4 marks/10 min) and lactation (mean +/- SE = 3.3 +/- 4.8 marks/10 min). Weaning allowed a gradual increase in chinning scores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255746 TI - Inhibitory effects of centrally and peripherally induced anosmia on mounting behavior in the female rat. AB - Adult ovariectomized female rats received a testosterone-propionate (TP)-filled silastic implant and were tested for mounting behavior seven days later. Exposure to estrous female urine but not to urine from ovariectomized females increased the number of TP-treated females that displayed mounting behavior. Olfactory bulb removal on its own and peripheral anosmia induced by intranasal ZnSO4 application impaired mounting behavior. These results are discussed with respect to the effects of anosmia on copulatory behavior in the male. PMID- 2255747 TI - Endogenous opioids modulate the cardiovascular response to mental stress. AB - The role of endogenous opioids in the cardiovascular response to mental stress was investigated in two controlled studies. In the first, cardiovascular, hormonal and psychological measures were made in a group of subjects before, during and after presentation of either a mental stress task or a non-stressful control task in the presence of naloxone (8 mg), an opiate antagonist, or an equal volume of saline. The study was carried out in random order and single(subject)-blind. Naloxone specifically enhanced the heart rate response to the stressful task but had no effect on blood pressure, plasma epinephrine or norepinephrine, or feelings of anxiety. Naloxone increased plasma cortisol and ACTH in both stressful and control tasks. A second, double-blind, study replicated the effect on heart rate. An endogenous opioid mechanism thus appears to inhibit the cardiovascular response to stress. PMID- 2255748 TI - Psychophysiological effects of early morning bright light exposure in young adults. AB - The effects of bright light on circadian rhythms in man are well documented. Nevertheless the theoretical basis and the rules for the practical utilization of light exposure as therapy need still to be better defined. The present study determined to what extent a 2-hr bright light exposure (0500-0700 h) improved the adjustment to an early rising in normal adults. Phase changes were assessed in subjective alertness, performance in several search tasks, time estimation, and a visual discrimination task, as well as in body motility, plasma cortisol concentrations, and body temperature. In comparison with a dim light exposure, the bright light resulted in increased motor activity during waking, in earlier peak of subjective alertness, and an improvement in performance speed in three out of five tasks in the morning. Cortisol and body temperature also were phase advanced. In summary, light applied to a portion of the circadian cycle sensitive to phase advance shifts influenced rhythms with strong endogenous components (temperature and cortisol), while other rhythms with strong exogenous components were more sensitive to sleep deprivation caused by the early rising time. PMID- 2255749 TI - Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and growth hormone responses to yohimbine in panic disorder patients and normal controls. AB - Eleven patients with a DSM-III diagnosis of panic disorder and seven normal controls received yohimbine (20 mg) or placebo orally in a double-blind paradigm on two separate days. Compared to normal control subjects, the panic disorder patients had similar behavioral responses to placebo but a greater anxiogenic response to yohimbine. Compared to placebo, yohimbine produced a significant increase in plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) levels (p less than 0.02), with a trend toward greater MHPG rises in the panic disorder patients compared to the normal controls. In the patients, but not in the controls, there was a significant positive correlation between yohimbine-induced peak changes in MHPG and increased ratings of panic anxiety. Yohimbine had no effect on plasma growth hormone (GH) levels in either patients or controls. These results are discussed within the context of the noradrenergic theory of panic disorder. PMID- 2255750 TI - Prolactin response to low-dose haloperidol challenge in schizophrenic, non schizophrenic psychotic, and control subjects. AB - Haloperidol was administered IV to 46 male psychotic inpatients and 28 male control subjects. A two-way analysis of covariance, with age as the covariate, revealed that DSM-III schizophrenics (n = 27) had a lower prolactin response to haloperidol than did the controls (n = 28). There were no significant differences between the prolactin responses in schizophrenics, patients with affective disorders (n = 7), and those with other psychoses (n = 12), which included patients with paranoia, schizophreniform, schizoaffective disorder, and atypical psychoses. These findings support the proposition that tuberoinfundibular dopaminergic dysfunction may occur in certain patients with DSM-III schizophrenia. PMID- 2255751 TI - Urinary 6-sulphatoxy melatonin levels within the menstrual cycle and in patients with premenstrual syndrome. AB - The present investigation examined the production of urinary 6-sulphatoxy melatonin (aMT.6S) during the early follicular and late luteal (premenstrual) phases in healthy, normal women and in patients with premenstrual syndrome (PMS). There was no significant difference in levels of aMT.6S on either day 6 or 26 of the menstrual cycle between control subjects and those with PMS. There also was no significant change in urinary aMT.6S levels within the menstrual cycle. These findings do not support an involvement of melatonin in the development of PMS symptomatology and are not supportive of the proposed role of melatonin in regulating ovulation in humans. However, our analysis of 12-hr urine samples may have been insensitive to small, yet possibly biologically significant, changes in the amplitude and period of melatonin excretion during the early hours of the morning. PMID- 2255752 TI - [The importance of bone scintigraphy in the aftercare of patients with malignancies]. AB - The present review is concerned with the value of bone scanning in the follow-up of patients with malignant tumors. The scintigraphic sensitivity depends on the type of bone metastases. Osteoplastic metastases (e.g., from prostatic cancer) can be detected much more easily than purely osteolytic foci (e.g., of multiple myeloma). One controversial point is the role of bone scans in the follow-up of patients with breast carcinoma. This particular malignancy is used as an example to point out irrationalities in the recommendations on the selection of imaging modalities in routine follow-up. Such recommendations are based on the present knowledge of the tumor growth kinetics, which is still inadequate. In view of this, follow-up strategies should not be based solely on statistical and epidemiological considerations and cost-benefit ratios. PMID- 2255753 TI - [Diagnosis and differential diagnosis of a peritoneal carcinosis. Conventional techniques, sonography, computed tomography, magnetic resonance tomography]. AB - Based upon the results obtained in 346 patients, the diagnostic value of conventional techniques, ultrasonography, computed tomography and magnetic resonance imaging in the detection of peritoneal tumor spread is analyzed. Since such signs as ascites, mesenteric and omental infiltration and peritoneal masses are non-specific, various conditions have to be considered in the differential diagnosis. None of the imaging modalities can exclude intraperitoneal tumor spread. PMID- 2255754 TI - [Magnetic resonance tomographic study of aortic isthmus stenosis]. AB - We present four patients with coarctation of the aorta, whose work-up was facilitated by MRI. Magnetic resonance has the potential for displacing angiography in imaging these patients. PMID- 2255755 TI - [A posttraumatic pseudoaneurysm of the hepatic artery. Duplex sonographic diagnosis and follow-up in spontaneous thrombosis]. AB - Guided percutaneous biopsy represents a standard procedure in establishing specific diagnosis of focal liver lesions. We report a case of left hepatic artery pseudoaneurysm diagnosed by means of Duplex Doppler sonography (DS) immediately before percutaneous biopsy should be performed. Selective hepatic artery embolization was planned, but spontaneous thrombosis of the pseudoaneurysm was documented by DS and angiography, respectively. DS is able to identify the vascular nature of a lesion and is helpful to avoid puncture of an aneurysm. PMID- 2255756 TI - [CT follow-up studies of conservatively treated lumbar intervertebral disk herniation]. AB - A CT study was carried out on 43 patients with low back pain and sciatica who were treated conservatively. They were followed up for over 20 months (mean) clinically and monitored by CT before and after treatment. Initially, 38 of them had herniation and 5 had protrusion of the disc. At the time of follow-up only 24 of the initial 40 patients still had neurological deficits. In 76.7% of the patients CT showed an improvement (clear regression in 15 patients, moderate decrease in 18 patients). A favourable tendency towards regression was observed in disc herniation at the L5-S1 level and in cases showing sequestration. The prognosis was unfavourable in herniations at higher levels than L5-S1 and in lateral herniation reaching the intervertebral foramen. PMID- 2255757 TI - [Delayed damage to the hip joint in competitive sports]. AB - There is rather little literature about hip disease in later life of former elite athletes. This running prospective study is concerned about precisely this question. Conclusive results are not yet available. But there are signs for a tendency towards increased formation of degenerative hip disease (or even premature arthrosis) in hurdling, jumping, decathlon, and probably in long distance running. Possible causes are mentioned (epiphysiolysis in hurdling?). Short outline about biomechanics and relationship of involved forces. The intention is to stimulate enhanced research of this problem. PMID- 2255758 TI - [Christian social ethics and medicine]. AB - In bygone centuries, the maxim of doing no harm was enough to define intervention by a doctor; now, in contrast, dealing with the possibilities opened up by modern medical technology demands increasingly careful observance of the moral virtue of the correct degree of moderation. The present ethical challenge when medical decisions have to be made is not simply to be allowed to do everything possible. The art of medical intervention has to be exercised with due respect for the concept of temperantia medici, which, however, has to have significance not only in the concrete individual case, but also in the wider context of social ethics, that is to say for health services as a whole. The anonymity resulting from increasing specialization, the tendency to think impersonally in terms of probabilities following the introduction of screening programmes with routine examinations and the connected legalization of medicine are addressed as particularly important problems in this respect; all these trends beset the personal doctor-patient relationship with difficulties and suggest the procedure with the greatest technological input as the safest and most convenient solution, thus making it difficult to find the correct degree of moderation. As a result of all this, modern medicine is evidently being regarded with increasing scepticism by wide sections of the population, a situation demanding an ethically appropriate return to the old medical virtue of moderation. PMID- 2255759 TI - [A lung tumor?]. PMID- 2255760 TI - [Genomic organization of the tRNA genes in Escherichia coli]. PMID- 2255761 TI - [Proteolytic processing of viral glycoproteins and its significance for viral pathogenicity]. PMID- 2255762 TI - [Protein dynamics revealed by an ultrafast time-resolved spectroscopy of tryptophan]. PMID- 2255763 TI - [Hybrid subtraction of mRNA using Oligotex-dT 30]. PMID- 2255764 TI - [Clinical aspects of human retroviral diseases]. PMID- 2255765 TI - The pharmacology of N-methyl LTC4; a metabolically stable LTC4-mimetic. AB - N-methyl LTC4 (NMLTC4) a synthetic analogue of LTC4, has been shown not to be a substrate for gamma-glutamyl transpeptidase. NMLTC4 produced contractions of the guinea pig ileum and trachea with pD2 values of 7.7 +/- 0.12 (n = 6) and 8.1 +/- 0.1 (n = 6) respectively, compared with values of 9.0 +/- 0.1 (n = 5) and 8.0 +/- 0.2 (n = 6) for LTC4. The concentration-response curve to LTC4 and NMLTC4 on ileum was displaced to the right by FPL55712. The corresponding pA2 values were 6.3 +/- 0.3 (n = 10) for LTC4 and 5.7 +/- 0.2 (n = 6) for NMLTC4. In the presence of acivicin, a gamma-glutamyl transpeptidase inhibitor, the LTC4 concentration response curve on trachea was displaced to the left, but the NMLTC4 curve was unaffected. The comparative potencies in the presence of acivicin on trachea indicate that LTC4 is approximately 6 times more potent than NMLTC4 whereas on ileum, in the presence of FPL55712 LTC4 is approximately 14 times more potent. In vivo NMLTC4 is a weak bronchoconstrictor substance being 20-30 less potent than LTC4. However, unlike the in-vitro studies the bronchospasm was significantly reduced by pretreatment with LTD4 antagonists. NMLTC4 administered intravenously produced a pronounced hypertensive effect which appeared to be due to peripheral vasoconstriction. PMID- 2255766 TI - A new prostaglandin E1 analogue (TFC-612) improves the reduction in motor nerve conduction velocity in spontaneously diabetic GK (Goto-Kakizaki) rats. AB - A new prostaglandin E1 analogue, TFC-612, was given orally to 2 month-old spontaneously diabetic GK (Goto-Kakizaki) rats for 3 months to ascertain its effects on reduced motor nerve conduction velocity (MCV). A high dose of this compound (0.3 mg/kg body weight) significantly restored MCV after 2 and 3 months of administration, although the low dose (0.03 mg/kg body weight) did not. In addition, 1 month administration of TFC-612 significantly improved the reduced MCV in aged (5 month-old) GK rats only in the high dose group (0.3 mg/kg body weight), but not in the low dose group (0.03 mg/kg body weight). Although TFC-612 significantly suppressed sorbitol accumulation in the sciatic nerves of GK rats in a dose dependent manner after 3 months administration, this suppression was not observed after either 2 months administration to 2 month-old GK rats or after 1 month administration to 5 month-old GK rats. Fasting blood glucose levels of all GK rats remained high throughout the experiments, regardless of TFC-612 administration. TFC-612's improvement on reduced motor nerve conduction velocity was related partly to suppression of sorbitol accumulation, but other factors, including microcirculation, may contribute significantly to this effect. These results suggest that TFC-612 may be beneficial in the treatment of diabetic nerve impairment. PMID- 2255767 TI - Effects of metal ions on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex. AB - The effects of Cu2+, Fe2+ and Zn2+ on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex were examined. Cu2+ and Zn2+ (0.05-0.5 mM) inhibited the activity of this enzyme in a dose-dependent manner. The concentration required for 50% inhibition was approximately 0.1 mM for Cu2+ and 0.15 mM for Zn2+. The inhibition by both metals was uncompetitive and non competitive with regard to NAD+ and prostaglandin E2, respectively, indicating that the mechanisms of the inhibition on the enzyme of both metals may be the same. Fe2+ had no effect on the activity of this enzyme. These results suggest that Cu2+ and Zn2+ have the potential to modulate the catabolism of prostaglandins by the kidney cortex. PMID- 2255768 TI - The effect of magnesium sulfate infusion on systemic and renal prostacyclin production. AB - Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4. PMID- 2255769 TI - Non-cancerous ulcer in the esophagus after radiotherapy for esophageal carcinoma- a report of 27 patients. AB - Twenty-seven patients with non-cancerous ulcers (NCU) (radiation ulcer) after radiotherapy for esophageal carcinoma are presented. Two-thirds of them had been misdiagnosed as uncontrolled or recurrent cancers, leading to improper management. Patients with NCU in the esophagus are characterized by having severe pain in the chest or back, especially on swallowing. On X-ray films, the lesions appear as superficial ulcerations with a line of demarcation above and below the ulcer margin. The wall opposite the ulcer is not usually involved and the ulcer infrequently invades the nearby organs. On conservative treatment, they usually heal and the symptoms are relieved. Seven out of 27 patients have survived from 20 months to 13 years without any evidence of disease. PMID- 2255771 TI - DNA damage and repair following treatment with ionizing radiation. PMID- 2255770 TI - Analysis of 5-iodo-2'-deoxyuridine incorporation in murine melanoma for photon activation therapy. AB - Quantitative evaluation of the dose enhancement obtained with analog nucleoside agents such as iododeoxyuridine (IdUrd) requires knowledge of the degree to which the thymidine (Thd) in DNA is replaced by IdUrd. In the present investigation, mice were infused with IdUrd using an intravenous infusion apparatus capable of delivering continuous multi-day infusions without restraining the mice. The absolute incorporation of IdUrd in DNA was measured by 125IdUrd label, both in whole tissue and extracted DNA, showing a good correlation between levels observed in DNA and whole tissue. Replacement in a Harding-Passey murine melanoma tumor carried in BALB/c mice approached 10%. In addition, a Neutron Activation Analysis (NAA) technique was developed which showed in vitro, a sensitivity sufficient to evaluate the % replacement of Thd by IdUrd in small biological samples with a sensitivity greater than 0.1 ppm, at 1% replacement in mg samples. This method can provide information on iodine substitution in DNA in humans where the use of a radioactive DNA-seeking substance would be undesirable. Analyses of IdUrd incorporation in cultured cells by NAA and 125I counting showed good agreement. PMID- 2255772 TI - Present and perspective role of radiology in cerebrovascular disease. PMID- 2255773 TI - Cerebrovascular disease: pathophysiology and clinical aspects. PMID- 2255774 TI - Cerebrovascular disease. A rational approach to diagnostic protocols. PMID- 2255775 TI - Role of computed tomography in cerebrovascular ischemia. PMID- 2255776 TI - MRI in cerebrovascular ischemic disease. PMID- 2255777 TI - Diagnostic ultrasound imaging. PMID- 2255778 TI - Angiography of epiaortic vessels. PMID- 2255779 TI - Angiography of the intracranial vessels. PMID- 2255780 TI - Magnetic resonance angiography of epiaortic vessels. PMID- 2255782 TI - Immunomodulating drugs in pneumology. PMID- 2255781 TI - Angioplasty of carotid arteries. PMID- 2255783 TI - Retroperitoneal involvement in sarcoidosis. AB - The presence of retroperitoneal lymphnodes is well known in sarcoidosis. We observed in two patients unilateral hydronephrosis (asymptomatic in one; dysuria in the other), and in one patient urine retention due to compression of both ureters; this patient also had jaundice due to lymphnode compression of the biliary tract. In another four patients we noted retroperitoneal lymphnodes without compression. We conclude that retroperitoneal impairment may be a previously unreported complication of Sarcoidosis. PMID- 2255785 TI - Sarcoidosis in Yugoslavia. AB - Although the first case of sarcoidosis in Yugoslavia was described immediately before the World War II, it was not before the 50's and the 60's that the disease started to be more frequently discovered. According to the evidence of pulmologic centres throughout the country, the incidence of sarcoidosis in 1988 was found to be the lowest in Macedonia (0.4 per 100,000 inhabitants). Since 1970, Yugoslavia has had its own Kveim-Siltzbach antigen, used in over 3000 patients. International World and European conferences on sarcoidosis aroused greater interest for sarcoidosis in Yugoslavia, particularly the Third European Conference on Sarcoidosis held in Novi Sad in 1980. Consequently, the Yugoslav Association on Sarcoidosis as an integral part of the WASOG has been organized this year. PMID- 2255784 TI - The role of T-lymphocyte subpopulation in bronchoalveolar lavage in pulmonary parenchyma diseases. AB - Cellularity and T-lymphocyte to T-lymphocyte subpopulation ratio were examined in 37 cases of interstitial pulmonary disease as well as in two healthy subjects in bronchoalveolar lavage (BAL) using monoclonal antibody indirect immunofluorescence technique. In BAL, active sarcoidosis cases (n = 18) were found to have increased T-lymphocytes of helper phenotype (CD4) accompanied by a markedly heightened CD4/CD8 proportion. Conversely, T-lymphocytes of the suppressor cytotoxic phenotype (CD8) with markedly reduced CD4/CD8 proportion predominated in the BAL of cases with hypersensitive pneumonitis (HP). Case group having sarcoidosis (S) after corticosteroid therapy (n = 11) showed a reduction in the proportion of T-lymphocytes (CD4) as well as in that of CD4/CD8 in BAL. An analysis of T-lymphocytic subpopulation in BAL could be helpful in diagnosing pulmonary interstitial disease, and give an insight into disease activity. PMID- 2255786 TI - Pulmonary sarcoidosis in the Nordic countries 1950-1982. II. Course and prognosis. AB - The review is based on studies of pulmonary sarcoidosis from Denmark, Finland and Sweden during 1950-1982, focusing on the course and prognosis of the disease. Cases with acute onset with chest X-ray stage I, fever, arthritis and erythema nodosum had a 85-90% remission rate during the first two years. The overall 5 year remission rate for stage I was 82%, stage II 66% and stage III 30%. Among cases with stage I, 2-5%, and among cases with stage II and III, 6-10% developed chronic pulmonary disease. Patients with stage I had a normal mortality rate, whereas those with stage II, III and IV had a rate threefold higher than expected due to sarcoidosis-related cardiopulmonary complications. PMID- 2255787 TI - Sarcoidosis and giant splenomegaly. AB - Splenomegaly is often a manifestation of sarcoidosis, but giant splenomegaly is rare. Only 25 cases of sarcoidosis presenting as massive splenomegaly have been reported. Splenectomy was performed before the diagnosis of sarcoidosis was made in more than half of these patients. Serious complications of giant splenomegaly including rupture, severe thrombocytopenia and hemolytic anemia were not consistently present preoperatively. A case of disseminated sarcoidosis presenting with giant splenomegaly and normal chest roentgenograms is described. Prednisone therapy improved the patient's pulmonary function testing while constitutional symptoms, splenomegaly and elevated angiotensin-converting enzyme levels completely resolved. Sarcoidosis should be considered in the differential diagnosis of massive splenomegaly. A trial of steroids is warranted as initial treatment, and in selected cases may prevent unnecessary splenectomy, thereby precluding a compromise in host defenses against encapsulated bacteria. PMID- 2255788 TI - Sarcoidosis of the nose: report of a case with nasal perforation. AB - We report a case of multisystem sarcoidosis with involvement of the nose and septal perforation in a young West Indian woman. We discuss the etiology of nasal perforation and prognosis of such a lesion. PMID- 2255789 TI - Hypertrophic osteoarthropathy in sarcoidosis. AB - This is the first report of hypertrophic osteoarthropathy associated with sarcoidosis. A forty-five year old black woman with clubbing, a history of bone pain, and a four year history of diagnosed sarcoidosis, was found to have symmetrical subperiosteal bone formation. PMID- 2255790 TI - Pneumothorax and pulmonary cavitation in a man with systemic sarcoidosis. AB - Sarcoidosis is a multisystem granulomatous disorder with protean manifestations. Physicians should be aware of potential unusual complications and this reminds one of the paradoxical affirmation that "rare events are always possible!" The case presented demonstrates two unusual consecutive complications: pneumothorax with lobar dissociation and primary acute pulmonary cavitation. Myocardium, liver and spleen were also involved. History and evolution suggest a relationship between sarcoid activity and alcohol consumption. PMID- 2255791 TI - Familial sarcoidosis: a case report. AB - The occurrence of sarcoidosis in more than one member in the same family is a fact that has been noted by many authors. It is now recognized as Familial Sarcoidosis, and nearly 450 cases have been reported in the world literature. Included in this figure are consaguineal cases as well as contacts without genetic relationship. The incidence of Familial Sarcoidosis (FS) is in striking contrast in the different series of recorded sarcoidosis cases. While some authors indicate 12% of the sarcoidosis total, others refer to up to 44.7% with an average of 7% in the literature. We report a new case of Familial Sarcoidosis that according to our knowledge of the literature is the first case referred to from Spain. PMID- 2255792 TI - Bilateral spontaneous pneumothorax and sarcoidosis. AB - We report on a 44-year-old smoking man with sarcoidosis stage III presenting with bilateral spontaneous pneumothorax. The diagnosis was confirmed by biopsies from the lung parenchyma, visceral pleura and bronchial mucosa. Bilateral pleurectomy was needed since long-term tube drainage turned out to be unsuccessful. PMID- 2255793 TI - Hypothalamic-pituitary dysfunction with adrenal insufficiency and hyperprolactinaemia in sarcoidosis. A case report. AB - In sarcoidosis neuro-endocrine disorders are rare. A case of systemic sarcoidosis is presented in which hypothalamic-pituitary adrenal insufficiency and hyperprolactinaemia occurred simultaneously. PMID- 2255794 TI - Koan Ogata (1810-1863). Physician, educator, humanist. PMID- 2255795 TI - Sarcoidosis or lymphoma? PMID- 2255796 TI - Pathophysiological evaluation of BALF cell findings in patients with pulmonary sarcoidosis: examination of activated T cells. PMID- 2255797 TI - Panel discussion: pathogenesis of sarcoidosis based on case study. PMID- 2255798 TI - A mimic of sarcoidosis: brucellosis. PMID- 2255799 TI - Natural and corticosteroid-induced osteoporosis in sarcoidosis: prevention, treatment, follow up and reversibility. PMID- 2255800 TI - Glucocorticoid receptor in active pulmonary sarcoidosis. AB - Glucorticoid receptor (GR) content of open-chest lung biopsies of 8 patients with active non treated pulmonary sarcoidosis was compared to 10 normal lungs. Results showed a higher GR level in sarcoid lungs (86.0 +/- 8.0 fMol/mg protein) than in control ones (8.2 +/- 3.1 fMol/mg protein). Our findings suggest that this increase is due to the accumulation of active cells in the sarcoid granuloma, possibly lymphocytes and or macrophages that may express cytosolic GR. The high level of this receptor in sarcoidosis may represent an indicator of the responsiveness of this disease to corticoids. PMID- 2255801 TI - Value of enumerating cellular constituents of bronchoalveolar lavage fluid in differentiating sarcoidosis and cryptogenic fibrosing alveolitis. AB - Based on the observations of cellular constituents in the BAL fluid in 73 patients with sarcoidosis and 18 patients with cryptogenic fibrosing alveolitis, various diagnostic criteria for differentiating these two disorders were examined. Receiver operator characteristics curve was constructed using different levels of lymphocyte percent (L) in the BAL fluid. Discriminant accuracy was improved if the percent of polymorphs (P) was also taken into account. A log transformation of the ratio L/P + 1 was normally distributed and most useful in differentiating sarcoidosis from cryptogenic fibrosing alveolitis. A formal analysis of results may be helpful in assigning likelihood ratios for the observations on cellular constituents of BAL in patients suspected to have sarcoidosis. PMID- 2255802 TI - Nosocomial pneumonia in the 1990s: update of epidemiology and risk factors. AB - Hospital-acquired pneumonia is the second most common nosocomial infection in the United States. Aspiration appears to be the major route for the entry of microorganisms into the lower respiratory tract. Nosocomial pneumonia may be caused by bacteria, viruses and fungi. Aerobic gram-negative bacilli and Staphylococcus aureus are the most common etiologic agents, but infection is usually polymicrobial. Risk factors for nosocomial pneumonia include host variables, colonization with nosocomial pathogens, and impaired response of pulmonary defenses to the microbial challenge. Bacteria causing nosocomial pneumonia may be part of the patient's endogenous flora, originate from the hands of hospital personnel, or result from the use of invasive devices. The mechanically ventilated patient has multiple risk factors that contribute to the high rate of nosocomial pneumonia. An understanding of the epidemiology and risk factors for nosocomial pneumonia is fundamental for implementation of preventive strategies to reduce patient morbidity, mortality, and hospital costs. PMID- 2255803 TI - Gram-negative colonization of the respiratory tract: pathogenesis and clinical consequences. AB - The normal upper and lower respiratory tract are not colonized by enteric gram negative bacteria (EGNB), but when serious illness develops, both sites may harbor these organisms. Colonization at either site is more likely when the severity of illness increases, and in critically ill patients, Pseudomonas species are the most common colonizing organisms, especially in the tracheobronchial tree. Many of the risk factors for colonization by EGNB have also been recognized as predisposing conditions for nosocomial pneumonia, and colonization may precede and predict this infection. Colonization should be viewed as a marker of a sick patient who had multiple host impairments; it is these defects that often allow colonization to progress to invasive infection. One pathogenetic mechanism that mediates colonization is an increase in epithelial cell bacterial adherence for EGNB. Many of the clinical conditions that favor colonization lead to an alteration in epithelial cell surface susceptibility to bacterial binding. Factors that influence adherence include cellular variables, bacterial surface characteristics and exoproducts, and the microenvironmental conditions at the airway surface. In order for adherence to mediate colonization, mucociliary clearance and other lower respiratory tract defenses must be abnormal. Based on an understanding of colonization pathogenesis, rational strategies for nosocomial pneumonia prophylaxis may emerge. PMID- 2255804 TI - Infection control and pneumonia prophylaxis strategies in the intensive care unit. AB - Conventional infection control approaches, such as dedicated surveillance and control programs and barrier isolation techniques, effectively interrupt acquisition of many pathogens and reduce infection rates in the intensive care unit (ICU). However, a substantial proportion of infections results from endogenous rather than acquired organisms and require that we also develop strategies to prevent the progression from colonization to infection. Studies of systemic antimicrobial prophylaxis for patients at risk for pneumonia have consistently failed to demonstrate benefit. Topical endotracheal prophylaxis succeeded in preventing pneumonia but was complicated by the emergence of intrinsically resistant gram-negative bacilli. More recently, a number of trails have evaluated selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antibiotics. These regimens have demonstrated a substantial impact on pneumonia and overall infection rates in ICU patients. Further investigation will define the role of selective decontamination in selected patient populations as well as address concerns over selection of resistance. Other strategies, including immunoprophylaxis, colonization-resistant devices, and methods to decrease bacterial adherence may also prevent progression from colonization to infection and will be the subject of future investigation. PMID- 2255805 TI - Invasive techniques in the diagnosis of bacterial pneumonia in the intensive care unit. AB - Bacterial nosocomial pneumonia represents the greatest infectious risk for morbidity and mortality for patients requiring intensive care and mechanical ventilation. The occurrence of purulent respiratory secretions and new infiltrates on chest radiograph generally necessitates broad-spectrum antibiotic therapy due to the lack of a safe, reliable method of determining the presence or absence of bacterial pneumonia. This article reviews the currently available invasive techniques for the diagnosis of bacterial pneumonia in the intensive care patient, with particular emphasis on the bronchoscopic methods using protected specimen brushes and bronchoalveolar lavage. The reliability, risks, and techniques of the various procedures are compared and contrasted. PMID- 2255806 TI - Approach to therapy of respiratory infections in the critical care setting. AB - Therapy of pneumonia in the critical care setting includes intravenous antibiotics and supportive care. Since the etiologic agent of infection may not be clear, empiric broad-spectrum antibiotic regimens are often used. Combinations of beta-lactam and aminoglycoside agents are particularly popular regimens due to the high incidence of gram-negative bacillary and Staphylococcus aureus pneumonias in the critical care unit. Several new approaches to treatment of pneumonia in the critical care setting are being evaluated, including single agent empiric coverage using a broad-spectrum beta-lactam agent; broad-spectrum quinolones, such as ciprofloxacin; intrabronchial aminoglycoside instillation therapy; and passive immune therapy with immunoglobulins and monoclonal antibodies. PMID- 2255807 TI - The management of symptomatic hyponatremia. PMID- 2255808 TI - Hypokalemic states: current clinical issues. PMID- 2255809 TI - Magnesium deficiency. PMID- 2255810 TI - Hypophosphatemia: pathophysiological and practical aspects of its therapy. PMID- 2255811 TI - Refractory hypertension: definition, prevalence, pathophysiology, and management. PMID- 2255812 TI - Diagnostic considerations in autosomal dominant polycystic kidney disease. PMID- 2255813 TI - The nephrotoxicity of chemotherapeutic agents. PMID- 2255815 TI - Professional communication skills. PMID- 2255814 TI - Hepatorenal syndrome. PMID- 2255816 TI - Communication: what happens during the first encounter between patient and physiotherapist? AB - First encounters between patients and physiotherapists have been video-taped and analysed as part of a research-project. Emphasis was on both functional assessment and patterns of interaction. Three groups of physiotherapists participated; manual therapists, psychomotor therapists, and district physiotherapists. The three groups used different approaches when examining their patients. Thus they conveyed different messages of content, roles, and relationships. Commonly, communication is discussed and analysed separately from diagnostic and therapeutic activity. Rejecting such separation, it is argued that it is important to highlight the way in which physiotherapists relate to their patients through their professional actions. The focus in this article is the implicit communication in the physiotherapist's examination. For physiotherapists, as for doctors, the body is the basis of their work. It is emphasized that it is especially important to discuss the body in connection with implicit communication. PMID- 2255817 TI - Hip fractures in primary health care. Evaluation of a rehabilitation programme. AB - The routine follow-up of hip fracture patients was transferred from the Orthopaedic Department, Lund University Hospital, to the primary health care districts in 1985. The medical state and social functions of all 298 patients during the first 12 months of the follow-up rehabilitation programme were registered. Before fracture, 61% lived in their own homes, 22% in old people's homes, and 14% in geriatric hospitals or nursing homes. Four months after fracture, 13% were dead, 47% were living in their own homes, 14% were in old people's homes, 25% in geriatric hospitals or nursing homes, while the rest were in other types of institutional residence. Of patients coming from their own homes, 75% were back at home four months after fracture and their social and functional status were as good as before fracture. The study has shown that routine check-ups at the orthopaedic department can be omitted. Follow-up in primary health care without radiography and orthopaedic expertise gives equally good functional results as in previous studies, provided that patients with pain and walking problems from the hip are guaranteed rapid specialist treatment. PMID- 2255818 TI - Food habits and infant feeding in newly resettled refugee families from Chile and the Middle East. AB - Food habits and infant feeding patterns of 45 newly resettled refugee families from Chile and the Middle East were studied in the suburbs of Stockholm. The social background of the sample was mixed and the level of maternal education high with the exception of the rural Kurds from Turkey. Children from rural Middle East areas had been breastfed for longer periods than the children from urban areas. Solid and semi-solid foods were introduced late in the Middle East. Chileans had a characteristic meal pattern, emphasizing lunch and often replacing dinner with a light meal. Resettled Chileans and Middle Easterners had a varied and well balanced diet with the characteristics of each culture. Foods containing sucrose were consumed frequently in both refugee groups. PMID- 2255819 TI - Failure to keep appointments at a community health centre. Analysis of causes. AB - The scheduled appointment system in primary care clinics became popular recently in Israel. Failed appointments created a problem for the doctors, patients and the clinic in Netivot. During 11 months, 2,317 appointments were surveyed. The survey showed 36% of failed appointments, with a decrease to 28% one year later. Rates of failed appointments were 38% for the paediatric population, 35% for adults, and 34% for pensioners. Market days and holidays predisposed to more failed appointments, representing community customs. The presence of a chronic disease that needed follow-up ensured a higher rate of attendance (76%), especially among the paediatric population (92% attendance rate). By contrast, a geriatric patient with an acute disease had difficulty attending the clinic (only 16% attending). 512 people (35% of the population) were responsible for the 827 failed appointments, and among them only 12% of the population accounted for 59% of the failed appointments. These findings have important implications in the planning of an appointment system in an urban health centre, and they strengthen the assumption that a small number of patients cause a large number of failed appointments. PMID- 2255820 TI - Well-being among 50-year-old people. The population study "50-year-old people in Kungsor". AB - Self-assessed well-being has been shown to be related to earlier medical events and to be a predictor of mortality. 50-year-old men and women (n = 314) in Kungsor were invited to an examination for traditional risk factors for cardiovascular diseases and different aspects of self-assessed well-being. The differences between men and women concerning their well-being could not explain the differences in the expected mortality between the sexes. A well-developed social network and physical exercise were the most positive determinants of well being, while drug intake, angina pectoris, and smoking were the most negative. PMID- 2255821 TI - Patterns of care in patients utilizing both primary health care and psychiatric care in a Swedish health district. AB - Patterns of care in all patients (N = 546) establishing contact with both primary health care and psychiatric care were studied during 1984 (N = 252) and 1986 (N = 294) in a Swedish health district. Utilization of primary health care was not affected by the sectorization of the psychiatric care organization, while there was a significant increase in utilization of outpatient psychiatric care. Patients with a higher number of visits in outpatient psychiatric care had a lower number of visits in primary health care. The utilization of care was unevenly distributed in the sample; 25% of the patients accounted for almost 60% of the visits in both care organizations. The mental health problems were identified in primary health care in 40% of the patients. This group of patients seemed to be defined as belonging neither to specialized psychiatric care nor to the general practitioner level of primary health care. PMID- 2255822 TI - Doctors' characteristics and practice patterns in general practice: an analysis based on management of urinary incontinence. AB - Six case histories concerning female urinary incontinence were mailed to 191 randomly selected general practitioners (GPs) in Norway, of whom 139 (73%) replied. Great variations in suggested investigations and treatment were found between individual doctors. Four explanatory variables were examined: doctors' sex, years since graduation, urban/rural location, and GP specialization. GP specialists treated fewer patients adequately than non-specialists. Experienced female doctors instructed more patients in pelvic floor exercises, prescribed more oestrogens, referred more patients, and also indicated the possibility of surgery more frequently than their colleagues. Nevertheless, patient management is largely independent of a doctor's sex and age, practice location, and GP specialization. PMID- 2255823 TI - Proctosigmoidoscopy in primary health care. AB - Of 282 patients who underwent rigid proctosigmoidoscopy (PSS) in primary care in the city of Vasteras during 1985, 5.7% had polyps or tumours in the rectum. Barium examination of the large bowel was performed on 194 of these 282 patients and showed polyps or tumours in 6.2%. Use of these two methods led to diagnosis of polyps or tumour in the large bowel in 9.6% (27/282). Polyps were found by both methods in only one patient. Of four patients with tumours, two were discovered by barium examination and two by PSS. Barium examination and PSS complement each other in the search for polyps and tumours in the large bowel. PMID- 2255824 TI - [Suicide in adolescents]. PMID- 2255825 TI - [Prenatal prevention of child abuse. 10-year-experience at the University Maternity Center of Liege]. PMID- 2255826 TI - [20 years of screening for toxoplasmosis in pregnant women. The Liege experience in 20,000 pregnancies]. PMID- 2255827 TI - [Fetomaternal hemorrhage: a cause of fetal morbidity and mortality]. PMID- 2255828 TI - [What is your roentgen diagnosis? Rectal drug body packing]. PMID- 2255829 TI - [The importance of often undiagnosed palpebral disorders]. PMID- 2255830 TI - [Anatomy and physiology of the eyelids]. AB - The eyelids take a prominent part in the protection from the anterior structures of the human visual system and in its maintenance. For moving 14,000 times a day and for producing and eliminating a three layers transparent fluid which is not thicker than eight microns, it's not surprising to find eight different layers in the upper eyelids or five different glands between the lashes and the upper fornix. PMID- 2255831 TI - [Congenital malformations of the eyelids]. AB - Congenital malformations of the eyelids have been classified in many ways, considering their various origins. The author proposes hereby a simplified classification concentrated on the therapy: 1. isolated malformations of one or two eyelids 2. palpebral anomalies associated with a more extensive craniofacial malformative syndrome 3. congenital tumors On this basis the author examines the most frequent malformations: blepharoptosis, coloboma, epicanthus, blepharophimosis, microblepharism and some congenital tumors. For each of these lesions, a surgical treatment is proposed and illustrated. PMID- 2255832 TI - [Eyelid tumors]. AB - This review is intended to every general practitioner who is dealing with the daily problems of benign cystic palpebral tumors. Clinical presentation and treatment are reviewed. The necessity to recognize and treat malignant tumors of the eyelids early is re-emphasized. PMID- 2255833 TI - [Eyelid injuries]. AB - The eyelids not only protect the ocular globe, but also keep it wet and transparent. In the case of a palpebral wound the survival of the ocular globe is perhaps at stake. Corrective reconstruction of a palpebral wound must be considered as quickly as possible in order to restore eyelid shape and mobility. A facial emergency must be treated along the lines of an immediate reconstruction. A completely successful restoration must see to the prevention of complications associated, on one hand to poor adaptation of the wounded edge engendering a deformed eyelid, a coloboma at the free edge, malpositioning (entropion or ectropion), or an acquired ptosis. On the other hand, stenosis of the lacrymal canaliculus will lead to epiphora. Both complications present later difficulties for treatment. PMID- 2255834 TI - [The aging eyelid]. AB - The ocular adnexal tissues share the progressive loss of tone and bulk, common to many aging tissues. As a result of these progressive involutional changes lid anatomy is altered inducing senile ptosis, ectropions, entropions, canthal laxity and epitheliomas. A better understanding of these conditions allows more appropriate surgical management. Senile ptosis is an acquired ptosis usually due to dehiscence or disinsertion of the levator aponeurosis (below the orbital septum); surgery aims to reattach it to the tarsal plate via either anterior or posterior approach. Senile ectropions and entropions share several aetiologic factors: horizontal laxity, lid retractors, laxity migration of the preseptal orbicularis for senile entropion; stretching of the canthal tendons, secondary skin retraction and conjunctival thickening for senile ectropion. The entropion requires the association of horizontal lid shortening, lower eyelid retractors shortening, skin blepharoplasty with deep sutures (between preseptal and pretarsal orbicularis). In some cases of senile ectropions, the horizontal shortening of the eyelid by a full-thickness pentagon resection with shortening of the lower eyelid retractors must be associated with a medial canthal tendon plication and skin graft. PMID- 2255835 TI - [The role of botulinum toxin in the treatment of essential blepharospasm]. AB - Benign essential blepharospasm is a focal dystonia consisting in involuntary closure of the eyelids. Until early 80's, therapeutic modalities included only psychotropic drugs, biofeedback and surgery, which showed limited efficiency. Recently, it has been suggested to inject botulinum toxin in affected palpebral orbicularis muscles. Used in several thousands of patients, it has been found that this procedure provides significant temporary relief from spasms of the eyelids. Local side effects are minimal, and no systemic side effects have been demonstrated in patients with blepharospasm treated with botulinum toxin. PMID- 2255836 TI - [A case from practice (199). Perforated appendix with tubovaginal purulent drainage]. PMID- 2255837 TI - A simple deterministic model for bancroftian filariasis transmission dynamics. AB - A differential equation model for bancroftian filariasis transmission dynamics is developed. Fluctuations of the mosquito vector population are related to environmental variables such as climate and vector control operations. Prevalence in the mosquito population and mean worm burden in the human population are considered. The behaviour of the model is compared with epidemiologic and entomological data from Pondicherry (South India). The model enables one to make predictions on the effect of future control operations. PMID- 2255838 TI - Experimental ocular onchocerciasis: local and systemic antibody and cell-mediated immune responses. AB - Hartley guinea pigs injected subconjunctivally with Onchocerca lienalis (OL) microfilariae (Mf) develop punctate corneal opacities resembling the punctate keratitis of human onchocerciasis. Antibody production and antigen-induced proliferative responses were studied in conjunctival-associated lymphoid tissues (CALT), spleens (SL) and peripheral blood lymphocytes (PBL) from experimentally infected guinea pigs. Cultured single cell suspensions of CALT, SL and PBL were assayed for IgG1, IgG2, IgA and IgE antibody production. IgG1, IgG2, and IgA Onchocerca-specific antibodies were found in culture supernatants of CALT, SL and PBL. When initiated 10 days after a challenge injection of OL, CALT cultures produced antibody levels equal to or less than those produced by the corresponding SL cultures. When initiated 66 days after the last injection of Mf, CALT cultures produced significantly more antibody than the corresponding SL cultures. Blastogenic responses to OL Mf antigen were observed in peripheral and splenic lymphocytes of OL-infected guinea pigs. Animals given subconjunctival injections of Mf followed by treatment with a microfilaricide had greater responses to OL antigen than those given Mf alone, while responses to phytomitogens were similar in drug-treated and non-treated animals. The CALT was locally immunologically responsive against the subconjunctivally injected OL Mf, with the capacity for localized memory responses. The local immunologic responses to conjunctival Onchocerca microfilariae may play a significant role in the immunopathological reactions of ocular onchocerciasis. PMID- 2255840 TI - Cloning of specific diagnostic antigens of Onchocerca volvulus. AB - Specific, serological diagnosis is one of the main goals in onchocerciasis research. To date this objective has been hampered by (a) scarcity of parasite material, and (b) antigenic cross-reaction between Onchocerca volvulus and other nematode species. In order to obtain specific antigens, and in amounts suitable for study, molecular biological techniques have been adopted. A lambda gt11 cDNA expression library prepared from O. volvulus adult female worms was screened using infected human sera from onchocerciasis patients and rabbit hyperimmune sera raised against Onchocerca and genus-specific Onchocerca antigen extracts. Five clones were selected and their inserts expressed as beta-galactosidase fusion proteins. The fusion proteins were examined using individual sera from patients with O. volvulus or Wuchereria bancrofti infections. Three of the fusion proteins were recognised by more than 80% of O. volvulus sera and exhibited weak reactivity with a few W. bancrofti sera. One of these three clones was recognised to a significantly greater degree by sera from sowda than from generalised onchocerciasis patients. PMID- 2255839 TI - Ivermectin for treatment of bancroftian filariasis in French Polynesia: efficacy in man, effect on transmission by vector Aedes polynesiensis. AB - Forty male Polynesian W. bancrofti carriers with mf counts greater than or equal to 20/ml were treated with a single ivermectin 50, 100, 150 or 200 mcg/kg dose. Following therapy, mf levels fell to less than 1% of pretreatment levels in the carriers treated with the 3 highest doses. After one month, negativation rate was 40% in patients treated with a 50 mcg/kg dose, significantly lower than in patients treated with higher doses. Recurrence of microfilaremia was observed by 3 months, mf recurrence percentages were significantly lower in patients treated with the 3 highest doses than in patients treated with a 50 mcg/kg dose. At 6 months, mf recurrence percentages reached 49.8, 12.6, 14 and 5.4% of pretreatment levels in carriers treated with 50, 100, 150 and 200 mcg/kg, respectively. No significant difference was observed between mf levels by group at 6 and 12 months. With respect to efficacy, a dose greater than or equal to 100 mcg/kg appeared superior to 50 mcg/kg dose; no significant difference between the 3 highest doses was observed. Some patients developed headache, myalgia and fever within 24 hours following therapy, none of adverse reactions were considered serious. In vector Ae. polynesiensis fed on carriers 6 months after treatment, average numbers of mf ingested and average numbers of L3 cephalic larvae were lower than those observed in mosquitoes fed on non-treated carriers with comparable mf counts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2255841 TI - Urban epidemiology of Schistosoma intercalatum in the city of Bata, Equatorial Guinea. AB - In a cross sectional study, 1221 individuals were enrolled to determine the urban epidemiology of Schistosoma intercalatum in the city of Bata, Equatorial Guinea. Bulinus forskalii was the only intermediate host for schistosomes found in the study areas. The only Schistosoma species detected in faeces was S. intercalatum. However, no Schistosoma eggs were found in urine. The overall prevalence of S. intercalatum infection was 21.2%. Although infected subjects were found in all age groups, peak prevalence and highest parasite load occurred in 5-14 years old children. But only 38 individuals (3.1%) had infection with more than 400 eggs per gram faeces. Thirty out of these (78.9%), were children between 5 and 14 years of age. In the heavily infected subjects (greater than 400 eggs/g. faeces) highly significantly more diarrhoea with microscopic and macroscopic blood in stool was present (p less than 0.0001). PMID- 2255842 TI - The relationship between rickettsia-like-organisms and trypanosome infections in natural populations of tsetse in Liberia. AB - A survey of natural populations of tsetse flies for rickettsia-like-organisms (RLO) has been carried out in Liberia. A population of G.p. palpalis showed a strong association between trypanosome and RLO infection; both infections were at low levels in this species suggesting that this population is highly refractory to trypanosome infection. A small sample of G. nigrofusca, considered the most effective vector of trypanosomiasis in Liberia, was found to have very high prevalence of RLO infection. The selection pressures which could determine RLO infection rate are discussed. PMID- 2255843 TI - Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12 hourly administration of 100 mg proguanil hydrochloride. AB - A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis. PMID- 2255844 TI - Effect of sinefungin on macromolecular biosynthesis and cell cycle of Plasmodium falciparum. AB - The growth of the malarial parasite P. falciparum was arrested by the adenine containing nucleoside sinefungin at the trophozoite stage. The synthesis of DNA, of polyamines and the specific proteins of the schizont stage were completely blocked by the drug. The inhibition of DNA synthesis was not due to a decrease in the amount of DNA polymerase, but to the depletion of polyamines which are required for DNA synthesis. PMID- 2255845 TI - Seasonal variation of wasting and stunting in preschool children during a three year community-based nutritional intervention study in northeast Thailand. AB - A nutritional intervention project was undertaken for three years in four villages located in a relatively prosperous irrigation area in northeast Thailand where sub-clinical undernutrition is still prevalent. Data were collected at each measuring pont from approximately 270 preschool children in four intervention villages. Approximately 120 children in three other villages in the same area served as controls for each measuring point. Various activities such as teaching nutrition, introducing supplementary feeding, and using and understanding weight charts, as well as home visits, were carried out in the intervention villages. An obvious improvement in the nutritional status of children in the intervention villages could be observed only after two years and nine months. In order that immediate action could be taken when a child was found to be undernourished or at risk of becoming undernourished in the near future, the nutritional indicator weight-for-height was used to assess the children's nutritional status. However, the best indicator determining the impact of the project was height-for-age. Intervention measures were successful in diminishing marked seasonal variations in the nutritional status observed in the study area. Statistical methods are given to evaluate a prospective study based on an incomplete repeated measure method. PMID- 2255847 TI - Marking snails with numbered, colored discs: a technique for identifying individual specimens. AB - Numbered, colored discs, measuring 2.5 mm in diameter, were evaluated under laboratory conditions as tags for marking and identifying individual snails. Discs were affixed to the shells of specimens of Helisoma duryi (Pulmonata: Planorbidae) with an adhesive supplied with the discs and with waterproof epoxy. All snails survived the initial tagging procedure and showed no observable behavioral responses to the tagging. The supplied adhesive, intended for use with terrestrial insects, was inadequate for securing the tags for prolonged periods under aquatic conditions. Use of waterproof epoxy, however, resulted in 100% tag retention for over 5 months without significant mortality. The permanence of the marks, their coding of individuals, the rapidity and ease with which the tags can be applied without causing behavioral changes or snail mortality suggest that this technique will be useful in studies requiring identification of individual aquatic snails. PMID- 2255846 TI - Seasonal variation in onchocerciasis transmission in the Santiago focus of Ecuador. AB - Man-biting rates and natural infection rates with filariae were determined for anthropophilic black flies in a preliminary survey during the wet and dry seasons at three localities, either hypoendemic or hyperendemic for onchocerciasis, in the Santiago onchocerciasis focus of Ecuador. Simulium exiguum was an efficient vector associated with hyperendemicity whereas S. quadrivittatum was thought only to sporadically transmit the parasite. Parasite transmission by these two species varied seasonally. Two other man-biting species, S. bipunctatum and S. escomeli, were discounted as vectors because of their largely zoophilic habit and rarity, respectively. The need is emphasised to investigate species distributions thoroughly before entomological surveys to obtain baseline data for vector control are investigated. PMID- 2255848 TI - Leprosy and other mycobacterial diseases. Proceedings of the Indo-EC symposium. Lonavla, India, November 6-9, 1989. Proceedings. PMID- 2255849 TI - Molecular studies on the antigens of Mycobacterium leprae. PMID- 2255850 TI - Interstrain variations of resistance and delayed type hypersensitivity in mice after infection with various substrains of Mycobacterium bovis (strains BCG) and after immunization with Mycobacterium leprae. PMID- 2255851 TI - Cytokine production and proliferative capacity of infiltrating cells in various forms of leprosy. PMID- 2255852 TI - An antigenic complex that restores ability in leprosy patients to kill Mycobacterium leprae--the probable molecular events identified by in vitro experiments. AB - The delipidified cell components of Mycobacterium leprae (DCC) obtained as an insoluble material was presented as an antigen by the macrophages of lepromatous leprosy patients. This resulted in in vitro lymphocyte proliferation and production of lymphokines, like IL-2 and IFN-gamma. This DCC induced culture supernatant was capable of activating patient macrophages through changes induced in the membrane, as monitored by same specific markers, before and after exposure to the supernatant. The activated macrophages could recognise M. leprae as an antigen to initiate cell mediated immunity and also recognise the bacilli as a pathogen to produce superoxide leading to the killing of phagocytosed M. leprae. Based on these observations, it is indicated that DCC could be a potent immunomodulatory restoring in the phagocytes of leprosy patients to kill M. leprae like normal resistant individuals. PMID- 2255853 TI - Recognition of ICRC and Mycobacterium leprae antigens by sera from leprosy patients. PMID- 2255854 TI - Role of antigen presenting cells in the immunogenicity of mycobacteria. PMID- 2255855 TI - Purification of recombinant Mycobacterium leprae 65-kilodalton antigen and murine antibody responses to intravenously administered recombinant protein. AB - Recombinant Mycobacterium leprae 65-kilodalton antigen has been purified by a combination of differential solubility, ion-exchange and hydrophobic interaction chromatography, and a method for the quantification of the antigen in large scale protein preparations developed. By injecting large amounts of the recombinant antigen intravenously into mice, a limited degree of specific suppression of antibody-response has been induced. PMID- 2255856 TI - Pitfalls in the ultrastructural analysis of mycobacteria, including Mycobacterium leprae. PMID- 2255857 TI - Drugs and drug development for chemotherapy of leprosy and tuberculosis, including M. avium infections. PMID- 2255858 TI - Recent concepts in the pathology of leprosy. PMID- 2255859 TI - Nerve damage, surgery and rehabilitation in leprosy. PMID- 2255860 TI - Clinical aspects of leprosy. PMID- 2255861 TI - Role of HLA linked factors in governing susceptibility to leprosy and tuberculosis. PMID- 2255862 TI - Genetics of tuberculosis susceptibility. PMID- 2255863 TI - Nerve antigen based serological tests for the diagnosis and prognosis of leprosy. PMID- 2255864 TI - An overview of the current status of serological techniques in the epidemiology of leprosy. PMID- 2255865 TI - Mycobacterium leprae antigens and their utility in immunodiagnostics of leprosy. PMID- 2255866 TI - A candidate anti-leprosy vaccine from ICRC bacilli. PMID- 2255867 TI - Immunotherapeutic trials with a candidate anti-leprosy vaccine based on Mycobacterium w. PMID- 2255868 TI - Continuous arteriovenous and intermittent hemofiltration in renal failure. AB - The clinical applications of continuous arteriovenous and intermittent hemofiltration (CAVH and IHF) have changed the concept of renal failure treatment which was previously understood to be hemodialysis (HD). To perform such treatments a reliable vascular access is a vital priority. Unfortunately, multiple vascular access problems are frequently seen among chronic HD or HF patients despite the reliability of the conventional arteriovenous fistula. In this study a needleless prosthetic vascular access device (Hemasite) has been tried (32 devices in 28 HD/HF patients) as an alternative solution. The five-year follow-up showed that the Hemasite device offered an immediate and reliable vascular access with adequate blood flow. The one-year cumulative survival rate was 55%. Thrombosis and infection were the two main causes for the implant loss. On the other hand, evaluation of our experience with acute vascular access in acute renal failure (ARF) in 76 patients showed that the most commonly used one was the Buselmeier shunt (75%), followed by the femoral catheters (23%) for femoral vessels catheterization, and the Scribner shunt (2%). The Buselmeier shunt gave adequate blood flow. It was safe and easy to manipulate in case of trouble during treatment (e.g. clotting). The outcome of CAVH as a first choice treatment modality for ARF in our centre, since 1982, was evaluated in 40 critically ill intensive care patients during the period July 1987-December 1988. The total survival improved from 45% (in a previous and similar study) to 55%. However, CAVH was found of limited role in uremic control in severe hypercatabolic states. In order to find an alternative solution, CAVH and continuous hemodialysis (CAVHD) were compared in 13 ARF patients. Better results in uremic control were achieved with CAVHD. The net ultrafiltration (UF) volume was lower in CAVHD. Furthermore both UF and diffusion could be combined during CAVHD treatment to give freedom for nutritional support as well as fluid removal. Renal failure patients are prone to infections because they are often critically ill, in case of ARF, or because of their disturbed immune system in case of chronic renal failure. Such patients are in need of urgent and adequate antibiotic treatment. Both renal failure and IHF create difficulties in antibiotics dosing. The pharmacokinetics of a potent broad spectrum antibiotic (imipenem/cilastatin) was studied during IHF for the purpose of dose adjustment. 75% of the given dose was eliminated by HF. Dosage recommendations were given. Fluid overload is a common finding in renal failure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2255869 TI - Pharmacokinetic and pharmacodynamic studies on recombinant human erythropoietin. AB - In order to optimize the treatment of anemia in uremic patients the pharmacokinetic and pharmacodynamic properties of recombinant erythropoietin (r Epo) were studied after i.v., s.c. and i.p. administration. Both in healthy volunteers and in patient with chronic renal failure, the half-life of r-Epo after i.v. administration was short (about 6 h) in comparison with the commonly used dosing interval of 3 to 7 days. Hence, the minimum serum concentration during a dosing interval is expected to be less than 1% of the peak concentration. Absorption following a s.c. dose was slow, resulting in a markedly different concentration-time profile in comparison to i.v. dosing. The half-life was about 25 h and only approximately 25% of the given dose reached the systemic circulation. As a result of differences in concentration-time profiles, higher trough concentrations during s.c. dosing intervals may be expected in comparison to those occurring after i.v. dosing. When r-Epo was given i.p. (diluted in dialysate) the extent of systemic absorption depended on the dwell time in the peritoneal cavity. A long administration time was required to absorb an amount of r-Epo predicted from s.c. studies to be adequate to achieve the desired clinical effect. In spite of reduced bioavailability, s.c. treatment did not require higher r-Epo doses than i.v. treatment to maintain the desired hemoglobin concentration. On the contrary, a trend to a requirement for lower doses was detected. The pharmacodynamic and pharmacokinetic results strongly indicate a more efficacious concentration-time profile following s.c. administration. Since s.c. dosing also allows self-administration the use of this administration route is recommended. To simplify the treatment of anemic patients with r-Epo, a model was developed to predict the required weekly s.c. dose. To facilitate the use of this model a nomogram was constructed. PMID- 2255870 TI - Effects of parental occupational exposures on spontaneous abortion and congenital malformation. AB - Human reproduction is a complex process and can be disturbed in many phases by both host and environmental factors. Therefore, it has been difficult to distinguish the occupational causes of spontaneous abortion and congenital malformations from other factors related to the parents' characteristics and their living environment. The extrapolation of results of animal studies to humans is often complicated because there are structural and functional differences between the species and the mechanisms of harmful effects are seldom known. There is also a lack of conclusive epidemiologic studies on the topic. At present knowledge on the potential reproductive toxicity of even rather common occupational exposures is limited and in many cases only suggestive. Paternal exposure to organic solvents before conception and maternal exposure during pregnancy may have adverse effects on the pregnancy and offspring. Heavy physical work during pregnancy may increase the risk of spontaneous abortion. PMID- 2255871 TI - Fertility among Danish male welders. AB - Welding may be detrimental to the male reproductive system. Fertility was examined in a Danish cohort of 3702 male metalworkers over a follow-up of 47 674 person-years. Occupational histories were gathered by postal questionnaires. Information on births was obtained by record linkage to the Danish Central Population Register. Among persons who had ever worked as welders, the probability of having a child was slightly reduced the year after a year of welding exposure, even after control for differences in age, birth cohort, paternal parity, birth of a child in the preceding five years, smoking, and consumption of alcoholic beverages (odds ratio 0.89, 95% confidence interval 0.83 0.97). The reduction in fertility was associated with the welding of mild steel, but not with the welding of stainless steel. These findings are consistent with results of previous studies of time to conception and semen quality in welders. PMID- 2255872 TI - Spontaneous abortion among women using video display terminals. AB - This case-base study with a source population of 214 108 commercial and clerical workers investigated the risk of adverse pregnancy outcome among women working with a video display terminal (VDT) in Denmark. A subpopulation was obtained by register linkage between a trade union membership file, the Medical Birth Register, and the National Register of In-Patients. In two years 24,352 pregnancy outcomes were registered, 2248 spontaneous abortions were recorded, and a base sample of 2252 pregnancies was randomly selected. Data on VDT use, job stress, ergonomic factors, and life-style factors were collected with questionnaires sent to 6212 women and 426 employers. There was no increased risk of medically verified spontaneous abortion among women with VDT use. The relative risk for women exposed to any degree of use was 0.94 (95% confidence interval 0.77-1.14). Ergonomic work load and job stress were not confounders. PMID- 2255873 TI - Congenital malformations among children of women working with video display terminals. AB - In a case-base study among 214,108 commercial and clerical employees in Denmark the potential effect of the use of video display terminals on the risk of congenital malformations in pregnancy was investigated. The study base was identified by means of register linkage of the Medical Birth Register and the National Register of In-Patients. In the source population 24,352 pregnancy outcomes were registered, 661 of which with congenital malformations entered the case group, and a base sample of 2252 pregnancies was drawn. Data concerning the use of video display terminals, job stress, ergonomic factors, exposure to organic solvents, and life-style factors were obtained from postal questionnaires. The results of this study did not support the hypothesis that the use of video display terminals during pregnancy is associated with an increased risk of congenital malformations. PMID- 2255874 TI - Sensory perception in the hands of dentists. AB - The difference between the dominant and nondominant hands in the perception of vibration, temperature, and heat pain was compared between 26 dentists with long term exposure to high-frequency vibration and 18 with short-term exposure. The dentists with long-term exposure had larger vibration threshold differences than those with short-term exposure, both for digit II (exposed to high-frequency vibration) and for digit V (unexposed), whereas the temperature and pain thresholds were similar. The former group had neurological symptoms in the dominant hand more often than the latter. Vibration threshold differences of exposed digit II and unexposed digit V were higher for the symptomatic dentists than for the symptom-free dentists. Since the exposed and unexposed fingers were similarly affected, the neurological symptoms in the dominant hand of dentists with long-term exposure seem to have some other etiology than high-frequency vibration. PMID- 2255875 TI - Mercury exposure of different origins among dentists and dental nurses. AB - Mercury exposure was studied among dental personnel with the use of urinary mercury excretion rates and questionnaires. The study covered 314 dentists and dental nurses employed in public clinics and private practices in Stockholm. The obtained urinary mercury excretion rates were analyzed by stepwise regression for assigning them to different origins, such as environmental factors, number of amalgam surfaces, chewing of gum, kind of employment and profession, age, sex, amalgam handling time, and use of amalgam capsules. On the average the occupational contribution to the total urinary mercury excretion rate was small and of the same order as the contribution from their own amalgam fillings (approximately 2 micrograms of mercury/24 h). There were, however, individuals showing excretion rates close to the levels at which effects on the central nervous system and the kidneys have been reported. PMID- 2255876 TI - Micronuclei in epithelial cells from sputum of uranium workers. AB - The cytogenetic effects of exposure to radon progeny and cigarette smoke were assessed with the exfoliated-cell micronucleus assay among 99 uranium workers. Cells with micronuclei were determined in one sputum specimen from each worker. Exposure to radon progeny and smoking habits were classified from interview data collected at the same time as the sputum specimens. Underground miners were considered exposed to radon progeny, and the other workers were considered unexposed. Neither radon progeny exposure nor cigarette smoking had any appreciable effect on the prevalence of cells with micronuclei; the crude prevalence ratios for the two groups were 1.0 (95% confidence interval 0.7-1.4) and 0.9 (95% confidence interval 0.6-1.3), respectively. The effects of radon and smoking were not confounded by each other or by age, nor were they synergistic. These findings cast doubt on the use of sputum-based micronucleus assay in epidemiologic studies of other populations exposed to occupational or environmental lung carcinogens. PMID- 2255877 TI - Influence of indoor climate on the sick building syndrome in an office environment. The Danish Indoor Climate Study Group. AB - The influence of indoor climate factors on symptoms of the sick building syndrome was investigated in Greater Copenhagen, Denmark. Altogether, 2369 office workers in 14 buildings, where indoor climate measurements were made, filled out a questionnaire. Multivariate logistic regression analyses of the multifactorial effects on the prevalence of work-related mucosal irritation and work-related general symptoms among the office workers showed that the concentration of macromolecular organic floor dust, the floor covering, the number of workplaces in the office, the age of the building, the type of ventilation, and two easily recognizable factors, the shelf factor and the fleece factor, were associated with the prevalence of symptoms. PMID- 2255878 TI - Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation. AB - The toxicokinetics of alpha-pinene were studied in human volunteers exposed by inhalation (2 h, 50 W) in an exposure chamber on four occasions. The exposures were about 10, 225, and 450 mg/m3 (+)-alpha-pinene and 450 mg/m3 (-)-alpha pinene. The relative pulmonary uptake was about 60% for the higher exposures, and total uptake increased linearly with increasing exposure. The total blood clearance was high, about 1.11.h-1.kg-1. After the exposure was terminated, less than 0.001% of the total uptake was eliminated unchanged in the urine and about 8% in exhaled air. A long half-time in poorly perfused tissues indicates a high affinity to adipose tissues. There was a statistically significant exposure response relationship among five subjects who experienced irritation. Short-time exposure to alpha-pinene did not give rise to acute changes in lung function 20 min after the exposure. PMID- 2255879 TI - [Salmonella gastroenteritis: causes, sequelae, therapeutic perspectives]. AB - Enteric salmonella are the most frequently isolated pathogens of bacterial diarrhea in Switzerland. Since 1987, increasing numbers have been reported to the Federal Health Office. The causes of this rise in salmonellosis prevalence, which has been observed in a number of countries, are the high rates of contamination in different foods, mainly in poultry and eggs. It has been shown that the usual kinds of egg preparation are not suitable for the elimination of salmonella, which may also be found inside the egg-shells. The solution to this problem involves measures of veterinary epidemiology and food hygiene. The epidemiologic significance of the asymptomatic carrier is considered to be rather slight. However, prolonged excretion of salmonella repeatedly results in social and economic problems, because the carrier food handlers are excluded from work when and for as long as they are excreting salmonella. Current possibilities in antibiotic treatment for these and other salmonellosis patients are discussed. PMID- 2255880 TI - [Peroneal muscle atrophy with talipes cavus. Pyramidal symptoms and sensory disorders in one family. On the problem of the nosological classification of hereditary spinal diseases and polyneuropathies]. AB - We describe a family with peroneal muscular weakness and atrophy with associated pyramidal signs. Onset of obvious symptoms was usually after the age of 50 years, but history pointed to subtle symptoms at an earlier age. The disorder was of autosomal dominant inheritance. The muscle weakness involved only the legs. All affected persons remained independent as regards their ability to walk. Sensory disturbances were never significant for the affected individual. With regard to the neurographies, the disease could be classified as a form of hereditary motor and sensory neuropathy (HMSN). The clinical picture, however, allows the classification of the disease as a form of spinal muscular atrophy or spastic spinal paralysis. We discuss the diagnostic implications of such disorders, which involve both the peripheral and the central motor pathways. PMID- 2255881 TI - [An avoidable cause of parental anxiety and unnecessary medical workup: diaper crystals (pannolithiasis)]. AB - Five infants aged 6 to 23 months had a history of passing crystals in urine. They were not ill, but micturition was reported to be associated with pain in two of them. Physical examination was normal, and urinalysis and culture were negative. In one case we observed "jelly-like crystals" of about 2 mm diameter which dissolved spontaneously in tap water. When the parents were re-questioned it became evident that all used a new brand of highly absorbent diapers. "Jelly-like crystals" developed in our laboratory when the absorbent material of the new diapers was put in contact with urine or tap water. The new highly absorbent diapers help to keep the baby dry. However, "jelly-like crystals" may be observed and possibly alarm both parents and physicians. Information for parents and physicians may avoid unnecessary anxiety or medical workup. PMID- 2255882 TI - Historia morbi atrocis--2 new cases of spontaneous rupture of the esophagus (Boerhaave syndrome). AB - We report the case of two patients hospitalized within a few weeks of each other and both presenting with spontaneous rupture of the esophagus whose evolution proved fatal. We take the opportunity of drawing attention to this rare and challenging disease, which is often diagnosed too late. PMID- 2255883 TI - [Adjuvant systemic therapy in breast carcinoma in the 1990s: status of things and open questions]. AB - Adjuvant systemic therapy of breast cancer has been shown to reduce relapses and prolong survival in the women treated. This is true of all subpopulations studied. Six-month multidrug chemotherapy in premenopausal patients, and tamoxifen or short-term chemotherapy in postmenopausal patients, are the treatments of choice in reducing the risk of relapse. In the near future ongoing research may answer some of the open questions surrounding the definition of populations for which the risk of relapse justifies therapy and the optimum manner of using available therapies. The modest but real improvement in prognosis of operable breast cancer was obtained solely by means of clinical trials. Participation in clinical research programs is becoming medically and socially mandatory. PMID- 2255884 TI - [Energetics of the human body]. AB - Nature, as we know it, obeys the Laws of thermodynamics. The investigation into the energetics of the human body is an application of these laws to the human biological system. The First Law of thermodynamics, which has been verified many times in experiments on the human body, expresses the constraints of the conservation of energy and the equivalence between work and heat. It considers any energy change as equally possible, not in the least taking into account the irreversibility of a given process. The implications of the Second Law of thermodynamics, on the other hand, have never been examined in detail on the human body. This Law defines the direction in which an energy transformation can occur, as well as the equilibrium conditions of the systems. In this paper, we present the main results of a body of research, aimed at calculating the non reversible processes of the human body system by means of using the entropy concept as the main operator in applying the Second Law on physical and sometimes even non-physical systems. Determination of body composition was based on Magnetic Resonance Imaging (MRI). In addition, we used direct as well as indirect calorimetric techniques to measure the heat transfers between the human body and its environment, as well as oxygen consumption and carbon dioxide production. These measurements allowed us to compute various energy balances of a human body at rest. Furthermore, we studied also several aspects of energy exchange of the human body during muscular work. PMID- 2255885 TI - [Sports and arthrosis]. AB - Recent changes in lifestyle have considerably reduced the loads that joints have to bear through occupational stresses. It is now essentially during leisure time that most people use somewhat intensely their locomotive systems, mostly as sustained bouts of physical exercise. The physician is therefore led to examining critically these sports activities and their consequences. One has to be aware of the fact that some sports may bring about an articular overuse, partly through trauma and partly through microtrauma. Nevertheless, when reviewing recent literature on the implied relation between exercise and degenerative joint disease, one is amazed in observing how contradictory the current opinions are. This article intends to be both a review and a synthesis of the various factors which are commonly accepted as playing a role in the etiology of degenerative joint disease consecutive to exercise. We take into account by the same token the well-known advantages of physical activity such as prevention of cardiovascular disease and atherosclerosis, the enhancement of psychic well-being and the delaying of the onset of ageing. Thus, knowing which sports may promote degenerative joint disease under given conditions, the physician will be able to counsel people with an identified proneness to joint disease into undertaking more healthful physical workouts. PMID- 2255886 TI - [Isokinetic measurements of the stretch strength of the femoral quadriceps muscle in surfers in comparison to healthy, untrained persons]. AB - The strength of the quadriceps muscle of twelve male surfers who practice their sport for more than 10 years was compared with results of 15 male untrained persons. The concentric peak torque of knee extensors was measured every 10 degrees in a range from 90 to 20 degrees isometrically and dynamically with a constant angle velocity of 10 degrees/sec. The difference in torque between the left and the right leg is not significant, but there is a slight dominance in favour of the standing leg. The body weight related strength of the surfers was 3.2 Nm/kg indicating a higher strength characteristic compared to 2.7 Nm/kg of untrained subjects. Moreover the strength values of our group of athletes were above the value of 3 Nm/kg, which is referred to in the literature as representing a good training status. In view of these results it can be concluded that a long-lasting specific training like surfing will change the strength characteristics of the quadriceps muscles, although none of the surfers had undertaken an extensive strength training for the lower extremity. PMID- 2255887 TI - [The SPORTMED Commission of the ASS (Swiss Sports Association)]. PMID- 2255888 TI - Electronic earful. Cochlear implants sound better all the time. PMID- 2255889 TI - Trojan Cow. An embattled hormone raises social questions. PMID- 2255890 TI - Gene therapy. PMID- 2255891 TI - Living with AIDS--changes and challenges in the care of HIV disease. PMID- 2255892 TI - Microalbuminuria in diabetic care. PMID- 2255893 TI - Alcohol intoxication and alcoholism in acute male medical admissions. AB - In order to assess alcohol related morbidity in male hospital patients we studied all acute male admissions over a period of three months. 9.3% of patients were found to have detectable alcohol on admission (level greater than 4 mmol/l). A total of 28.3% of admissions were judged to be alcoholic by questionnaire (Michigan Alcohol Screening Test). These results suggest that acute intoxication in male hospital admissions is not as common as previously recorded. The prevalence of alcoholism, however, was disturbingly high and has significant implications for in-patient management. PMID- 2255894 TI - Gastric and colorectal cancers in Scotland: a study of the geographical distributions and selected associations. AB - The geographical distributions of gastric and colorectal cancers in Scotland were investigated by analysing the data available for those diseases in the Annual Reports of the Registrar General for Scotland. For gastric cancer, the standardised mortality ratios (SMRs) for the 234 traditional communities in 1969 73 and for the 56 districts in 1979-83 were calculated. For colorectal cancer, only the data for the latter period were available, and SMRs for that period were calculated similarly. Possible determinants on the resulting pattern of high and low SMRs were investigated. Gastric cancer was generally associated with industrial and urban environments, particularly in west central Scotland, although mortality in Dundee was high in both periods; this cancer also showed significant negative correlations with social class II. By contrast, colorectal cancer showed no strong geographical pattern, no urban-rural gradient, and no social class associations. The cancers showed a weak association with each other. PMID- 2255895 TI - Inter-observer variation in interpretation of chest X-rays. AB - 139 chest x-rays of children with solid tumours or leukaemia were examined independently by three observers (a radiologist and two physicians) and a consensus report determined. There was total agreement between observers on 40 x rays (29%). The radiologist agreed with the consensus report on a significantly greater number of x-rays (91%) than both physicians (62% and 46%). There was a high incidence of over-reporting of abnormalities by both physicians. This study reinforces the need for regular dialogue between radiologists and clinicians for optimum interpretation of chest x-rays. PMID- 2255896 TI - Migraine or amaurosis fugax? The value of ultrasound. AB - Episodes of uniocular visual loss in patients with classical migraine may be due to thromboembolism from atheroma in the internal carotid artery. Non-invasive testing may prove very useful in making the correct diagnosis particularly in patients with an approximately 50% pre-test possibility of disease. PMID- 2255897 TI - Exchange transfusion of whole blood in the treatment of cerebral malaria. AB - A case of cerebral malaria in a young British traveller, successfully treated by exchange transfusion of whole blood, is reported and the literature regarding the use of this technique in P. falciparum malaria is briefly reviewed. PMID- 2255898 TI - Fatal haemolytic anaemia complicating a case of common variable hypogammaglobulinaemia. AB - A fatal case of common variable hypogammaglobulinaemia (CVH) is described. The patient presented with fulminant haemolytic anaemia. Post mortem examination revealed evidence of chronic hypogammaglobulinaemia. PMID- 2255899 TI - Simpson and 'the discovery of chloroform'. AB - It is widely accepted that Sir James Young Simpson discovered the anaesthetic properties of chloroform and pioneered its application in surgery and midwifery. The name of Simpson is not infrequently also associated with the discovery of chloroform and of anaesthesia. Simpson certainly did not discover the substance chloroform or anaesthesia, there is doubt as to whether he discovered the anaesthetic properties of chloroform, and he may not have been the first person to administer chloroform anaesthesia to a patient. He did, however, play an important role in the introduction of chloroform anaesthesia particularly in midwifery and obstetrics. PMID- 2255900 TI - Epidermal growth factor. PMID- 2255901 TI - Zebrafish as developmental models. PMID- 2255902 TI - Publishing by--and for?--the numbers. PMID- 2255903 TI - Biomedical funds: IOM strikes back. PMID- 2255904 TI - Large-scale sequencing trials begin. PMID- 2255905 TI - Did cooler heads prevail? PMID- 2255906 TI - The concept of probability in safety assessments of technological systems. AB - Safety assessments of technological systems, such as nuclear power plants, chemical process facilities, and hazardous waste repositories, require the investigation of the occurrence and consequences of rare events. The subjectivistic (Bayesian) theory of probability is the appropriate framework within which expert opinions, which are essential to the quantification process, can be combined with experimental results and statistical observations to produce quantitative measures of the risks from these systems. A distinction is made between uncertainties in physical models and state-of-knowledge uncertainties about the parameters and assumptions of these models. The proper role of past and future relative frequencies and several issues associated with elicitation and use of expert opinions are discussed. PMID- 2255907 TI - How big is the universe of exons? AB - If genes have been assembled from exon subunits, the frequency with which exons are reused leads to an estimate of the size of the underlying exon universe. An exon database was constructed from available protein sequences, and homologous exons were identified on the basis of amino acid identity; statistically significant matches were determined by Monte Carlo methods. It is estimated that only 1000 to 7000 exons were needed to construct all proteins. PMID- 2255908 TI - A trans-acting factor that binds to a GT-motif in a phytochrome gene promoter. AB - The regulatory photoreceptor, phytochrome, controls the expression of numerous genes, including its own phyA genes, which are transcriptionally repressed in response to light. Functional analysis of a rice phyA gene promoter, by means of microprojectile-mediated gene transfer, indicates that a GT motif, GCGGTAATT, closely related to elements in the promoters of a number of other light-regulated genes, is critical for expression. Partial complementary DNA clones have been obtained for a rice nuclear protein, designated GT-2, that binds in a highly sequence-specific fashion to this motif. Mutational analysis shows that the paired G's are most crucial to binding. GT-2 has domains related to certain other transcription factors. Northern blot analysis shows that GT-2 messenger RNA levels decline in white light although red and far red light pulses are ineffective. PMID- 2255909 TI - Identification of a specialized adenylyl cyclase that may mediate odorant detection. AB - The mammalian olfactory system may transduce odorant information via a G protein mediated adenosine 3',5'-monophosphate (cAMP) cascade. A newly discovered adenylyl cyclase, termed type III, has been cloned, and its expression was localized to olfactory neurons. The type III protein resides in the sensory neuronal cilia, which project into the nasal lumen and are accessible to airborne odorants. The enzymatic activity of the type III adenylyl cyclase appears to differ from nonsensory cyclases. The large difference seen between basal and stimulated activity for the type III enzyme could allow considerable modulation of the intracellular cAMP concentration. This property may represent one mechanism of achieving sensitivity in odorant perception. PMID- 2255910 TI - Isotope-edited NMR of cyclosporin A bound to cyclophilin: evidence for a trans 9,10 amide bond. AB - The binding of a 13C-labeled cyclosporin A (CsA) analog to cyclophilin (peptidyl prolyl isomerase) was examined by means of isotope-edited nuclear magnetic resonance (NMR) techniques. A trans 9,10 peptide bond was adopted when CsA was bound to cyclophilin, in contrast to the cis 9,10 peptide bond found in the crystalline and solution conformations of CsA. Furthermore, nuclear Overhauser effects (NOEs) were observed between the zeta 3 and epsilon 3 protons of the methylleucine (MeLeu) residue at position 9 of CsA and tryptophan121 (Trp121) and phenylalanine (Phe) protons of cyclophilin, suggesting that the MeLeu9 residue of CsA interacts with cyclophilin. These results illustrate the power of isotope edited NMR techniques for rapidly providing useful information about the conformations and active site environment of inhibitors bound to their target enzymes. PMID- 2255911 TI - Detection of radial crossbridge force by lattice spacing changes in intact single muscle fibers. AB - Time-resolved lattice spacing changes were measured (10-millisecond time resolution) by x-ray diffraction of synchrotron radiation in single intact muscle fibers of the frog Rana temporaria undergoing electrically stimulated tension development during application of stretches and releases. Ramp releases, which decreased fiber length at constant speed, caused a lattice expansion. After the ramp, increasing tension during recovery was accompanied by lattice compression. Ramp stretches caused a compression of the lattice. While the fiber was held at a constant length after the stretch, tension decreased and lattice spacing increased. These observations demonstrate the existence of a previously undetected radial component of the force generated by a cycling crossbridge. At sarcomere lengths of 2.05 to 2.2 micrometers, the radial force compresses the myofilament lattice. Hence, the myofilament lattice does not maintain a constant volume during changes in force. PMID- 2255912 TI - gCap39, a calcium ion- and polyphosphoinositide-regulated actin capping protein. AB - The polymerization of actin filaments is involved in growth, movement, and cell division. It has been shown that actin polymerization is controlled by gelsolin, whose interactions with actin are activated by calcium ion (Ca2+) and inhibited by membrane polyphosphoinositides (PPI). A smaller Ca2(+)- and PPI-regulated protein, gCap39, which has 49% sequence identity with gelsolin, has been identified by cDNA cloning and protein purification. Like gelsolin, gCap39 binds to the fast-growing (+) end of actin filaments. However, gCap39 does not sever actin filaments and can respond to Ca2+ and PPI transients independently, under conditions in which gelsolin is ineffective. The coexistence of gCap39 with gelsolin should allow precise regulation of actin assembly at the leading edge of the cell. PMID- 2255913 TI - Requirement of ets-2 expression for Xenopus oocyte maturation. AB - A molecular clone of the Xenopus laevis ets-2 gene was isolated from an oocyte complementary DNA library. The amount of messenger RNA (mRNA) in each oocyte or embryo was almost constant during oogenesis and was maintained until the blastula stage of embryonic development, indicating that the observed 3.2-kilobase transcript is a maternal message. The only normal adult tissue in which ets-2 mRNA was detected was the ovary. Injection of antisense oligonucleotides homologous to the ets-2 sequence into oocytes led to degradation of the mRNA and blocked hormone-induced germinal vesicle breakdown. The ets-2 product is thus required for the meiotic maturation of Xenopus oocytes. PMID- 2255914 TI - Disruption of the human SCL locus by "illegitimate" V-(D)-J recombinase activity. AB - A fusion complementary DNA in the T cell line HSB-2 elucidates a provocative mechanism for the disruption of the putative hematopoietic transcription factor SCL. The fusion cDNA results from an interstitial deletion between a previously unknown locus, SIL (SCL interrupting locus), and the 5' untranslated region of SCL. Similar to 1;14 translocations, this deletion disrupts the SCL 5' regulatory region. This event is probably mediated by V-(D)-J recombinase activity, although neither locus is an immunoglobulin or a T cell receptor. Two other T cell lines, CEM and RPMI 8402, have essentially identical deletions. Thus, in lymphocytes, growth-affecting genes other than immune receptors risk rearrangements. PMID- 2255915 TI - Fetal brain grafts and Parkinson's disease. PMID- 2255916 TI - Introduction: genetics in hematology III. PMID- 2255917 TI - Genetics of the red cell membrane skeleton. PMID- 2255918 TI - Genetic deficiencies in specific immune responses. PMID- 2255919 TI - Genetic epidemiology of structural mutations of the beta-globin gene. PMID- 2255921 TI - Can we prevent the increasing prevalence of cataract among the elderly? PMID- 2255920 TI - The variable expression of sickle cell disease is genetically determined. PMID- 2255922 TI - The neuroleptic malignant syndrome. PMID- 2255923 TI - Hepatitis B vaccination--the present status. PMID- 2255924 TI - Prevalence of cataract among the institutionalized elderly in Hong Kong. AB - The Hong Kong 1981 Census found a high prevalence of blindness in the age group aged 65 and above. Visual defects short of blindness are also a special problem among the elderly and cataract is one of the most important causes. We have studied the prevalence of cataract among 546 subjects living in homes or hostels for the aged in a New Town in Hong Kong. Cataract was defined as having a lens opacity and visual acuity worse than 20/100 in either eye. A prevalence of 45% among men and 32% among women was found. There was significant difference in prevalence between men and women aged below 75 but little sex difference was noted for the older age groups. Among the cataract cases detected on screening, about half had not had the diagnosis made previously. The results confirm the need for more epidemiological and health care studies on the visual problems among the aged. PMID- 2255925 TI - Neuroleptic malignant syndrome in organic brain disease and physical illness. AB - The neuroleptic malignant syndrome is a serious complication associated with the use of antipsychotic drugs that has received a great deal of interest in recent times. Although its aetiology has not been fully understood, it often occurs in association with underlying brain disease and physical debilitation. Two such cases are described. The various hypotheses concerning the aetiology and pathogenesis of this condition are also discussed. PMID- 2255926 TI - A low dose oxytocin regime for induction and augmentation of labour. AB - A low dose oxytocin regime was used in Labour Ward, Alexandra Hospital for the induction and augmentation of labour. It utilised an oxytocin infusion administered in an arithmetic progression from 1 to 16 mU in a peristaltic infusion pump. A total of 100 patients (67 for augmentation and 33 for induction of labour) classified according to parity were studied. An overall vaginal delivery rate of 87% was obtained. The overall mean durations of labour for nulliparous and multiparous patients were 6.6 hours (S.D. +/- 2.9 hours) and 4.9 hours (S.D. +/- 2.8 hours) respectively. The mean induction delivery time for nulliparous patients was 6.4 hours (S.D. +/- 3.2 hours) and for multiparous patients it was 4.0 hours (S.D. +/- 2.2 hours). About 69% of the nulliparae and 94% of the multiparae who were induced delivered within 9 hours. All the induced patients delivered within 12 hours. Neonatal outcome was good as assessed by Apgar score. PMID- 2255928 TI - Depersonalization syndrome--a report of 9 cases. AB - Depersonalization is defined and the clinical characteristics of 9 patients presenting with Depersonalization Syndrome are discussed. The cases comprise 5 males and 4 females with an age range of 15-47 years, of which two-thirds presented with an acute onset of symptoms. The diagnosis is made on the patients' own descriptions of their symptoms. Criteria laid out by Ackner and ICD-9 are closely adhered to. The findings of the study are compared with those of Shorvon's 66 cases and similarities are found. Depersonalization symptoms described by Mayer-Gross are reviewed. That depersonalization itself appears to have an affective aspect and a somatic aspect is noted, and an explanation for both aspects is attempted. The resistance to various treatment is confirmed. PMID- 2255927 TI - Denitrogenation in pregnant women. AB - Forty-five pregnant females were studied with respect to the effectiveness of denitrogenation by the 3, 5, 7 and 9 rapid vital capacity breaths, and 3 to 5 minutes of normal breathing. It was found that 3 to 9 vital capacity breaths cannot effectively denitrogenate a pregnant patient when a circle breathing system with a gas flow of 8 litres/min is used. At least 3 minutes of normal tidal volume breathing should be given for proper denitrogenation or preoxygenation if the circle system is used for such a purpose. PMID- 2255929 TI - Melioidosis: epidemiology and antibiogram of cases in Singapore. AB - There has been an increased incidence of melioidosis in Singapore. The disease affects mainly males, older patients and a disproportionately higher number of Indians and Malays. Possible predisposing illness include diabetes mellitus. Most patients are bacteraemic. Mortality rate is 72% for bacteraemic patients, as compared to 32% for non-bacteraemic patients. Local strains of Pseudomonas pseudomallei have been consistently sensitive to ceftazidime, chloramphenicol and piperacillin, and nearly always sensitive to tetracycline. PMID- 2255930 TI - Brain laryngeal mask--study in 50 spontaneously breathing patients. AB - Brain laryngeal mask (BLM) was used to assess its suitability in 50 spontaneously breathing patients by one lecturer and 4 Medical Officers. Insertion of the laryngeal mask was successful at the first attempt in 42 patients, second attempt in 7 and third attempt in one. The incidence of airway obstruction secondary to downfolding of the epiglottis, which was corrected by reinsertion, was 16%. Post operative complications included clenching of teeth in 5 patients, vomiting in 2 and excessive salivation in 3. The incidence of sore throat was 10%. PMID- 2255931 TI - Orbital complications of acute sinusitis. AB - Orbital complications of sinusitis may occur either by spread along the venous system or by direct extension of infection between contiguous structures. The association between sinusitis and inflammation of the orbits has been known for centuries. But in the post antibiotic era there is a marked decline in the number of case reports in the literature. This paper presents 10 cases of sinusitis who had orbital complications. The classification of this disease complex as given by Chandler helps in planning the treatment. Groups I and II respond very well to antibiotics but in groups III, IV, V surgical intervention is necessary. Early identification and aggressive therapy reduces the morbidity of this disease. PMID- 2255932 TI - A comparison of buprenorphine and pethidine in analgesic supplemented anaesthesia. AB - A randomized trial comparing 2.5 and 5 micrograms/kilogram body weight of buprenorphine and 0.8 milligram/kilogram pethidine, intravenously for intraoperative use in a balanced anaesthetic technique, and for postoperative analgesia was carried out. Compared with pethidine, buprenorphine was shown to be a satisfactory analgesic for preoperative and postoperative use with little difference in the incidence of unwanted effects and much longer duration of action. Increasing the dose of buprenorphine did not give any significant advantage. PMID- 2255933 TI - Sleep apnoea syndrome--a report of 14 cases. AB - Patients with sleep apnoea syndrome suffer considerable morbidity and an increased mortality. We reviewed the characteristics of 14 patients with sleep apnoea syndrome (11 males and 3 females) who were studied since 1986. All were less than or equal to 60 years of age with the majority in their 4th and 5th decade. Obesity was present in 8 patients (57%) and hypertension in 6 (43%). Overnight sleep studies showed that 11 patients had obstructive sleep apnoea, 2 had central and one had predominantly mixed sleep apnoea. Ten patients (71%) had some form of nose and/or throat pathology. Tonsillectomy seemed an effective therapeutic procedure in those with upper airway obstruction due to enlarged tonsils. Four out of 5 patients had significant symptomatic improvement post tonsillectomy. Nasal continuous positive airway pressure was also effective in alleviating apnoeas and relieving symptoms in 4 other patients who had no obvious upper airway obstruction. A high proportion of our patients had obstructive sleep apnoea due to enlarged tonsils. Tonsillectomy offered a simple and effective therapy for such patients. Nasal continuous positive airway pressure was also effective in the treatment of obstructive sleep apnoea. PMID- 2255934 TI - Cytogenetic studies in women with primary amenorrhea. AB - Cytogenetic investigations were carried out on 117 women with primary amenorrhea who had been referred to our Genetics Laboratory by clinicians throughout Malaysia, after exclusion of other causes of the disorder. Thirty-six cases (31%) showed numerical or structural abnormalities of the sex chromosomes. These can be broadly classified into 4 main types, namely, presence of a Y chromosome (14%), X chromosome aneuploidies (8%), structural anomalies of the X-chromosome (7%) and lastly, presence of a marker chromosome (2%). Mosaics constituted 17% of the abnormalities observed, always in association with a 45,X cell line. There was no observable correlation between the phenotype of the patients and their respective abnormal karyotypes. The aetiological role of sex chromosomal abnormalities in these amenorrheic women is discussed. PMID- 2255935 TI - A clinical, laboratory and echocardiographic profile of children with acute rheumatic fever. AB - A retrospective study of 42 children with acute rheumatic fever admitted to Hospital Universiti Sains Malaysia from April 1985 to March 1989 was undertaken to assess the clinical, laboratory, echocardiographic aspects and outcome. The ages of the children ranged from 5 years 9 months to 11 years 11 months. There was no significant sex difference. 69.4% were admitted between November and April with a seasonal low between May and August. Sixteen children (38.1%) were hospitalised for recurrence of rheumatic fever. Carditis was the commonest manifestation and was seen in 28 (66.6%) children, followed by arthritis in 24 (57.1%), and chorea in 3 (7.1%). Echocardiography detected abnormalities in 24 out of 35 cases and the most common echocardiographic findings were poor coaptation of mitral valve (ten) left ventricular dilatation (ten), thickened mitral valve cusps (seven) and pericardial effusion (seven). In those children followed up, there were 2 recurrences while on secondary prophylaxis and complete recovery was seen only in 11 (26.9%). PMID- 2255936 TI - Chronic liver disease in Kuala Lumpur, Malaysia: a clinical study. AB - This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively. PMID- 2255937 TI - Chinese in west Malaysia: the geography of beta thalassaemia mutations. AB - The overseas Chinese in West Malaysia are almost exclusively from the south eastern provinces of China-Kwangtung, Fukien, and Kwangsi. To institute a comprehensive thalassaemia control programme for this region we have characterised the beta thalassaemia mutations in 16 Chinese patients from West Malaysia: 4 beta thalassaemia mutations were seen: a) an A----G substitution in the TATA box [-28 base pairs (bp)], an A----T substitution in codon 17 [17 A--- T], c) a 4 base pairs - TCTT deletion in codon 41-42 [frameshift mutation (FSC 41 42)], and d) a C----T substitution at the second intervening sequence (IVS 11) position 654. Similar mutations have been described in patients from the south eastern provinces of China. The delineation of the specific mutations present will enable effective prenatal diagnosis for beta thalassaemia of ethnic Chinese in West Malaysia to be instituted. PMID- 2255938 TI - The management of chronic non-gonococcal urethritis. AB - Non-gonococcal urethritis (NGU) is one of the most common sexually transmitted diseases today. Oral tetracyclines and erythromycin are well established choices of treatment. Despite adequate treatment, about 30-35% of NGU persist or recur. The cause of persistence or recurrence remains unknown. Prostate gland involvement has to be ruled out where indicated. A 4 to 6 week course of tetracyclines or erythromycin is suggested for persistent or recurrent NGU. Counselling to emphasize that chronic NGU is probably a self limited disorder would be of help. PMID- 2255939 TI - Testing for syphilis--rational use and interpretation. AB - Syphilis is a disease caused by a spiral organism, Treponema pallidum. Microscopy is useful in diagnosing syphilis in its primary stage while the serological tests are used for diagnosing primary secondary or latent stages of syphilis. The non specific serological tests are the non treponemal tests such as the Venereal Disease Laboratory Test (VDRL) and the Rapid Plasma Reagin Test (RPR). Both these tests are used as a screening test. The specific tests are the treponemal tests. The two common treponemal tests are fluorescent treponemal antibody absorption test (FTA/ABS) and the Microhaemagglutination assay for Treponema pallidum (MHA TP). These two tests can be used to confirm the diagnosis of syphilis. The usefulness of laboratory tests in the diagnosis of syphilis depends on the selection of the appropriate standard tests. PMID- 2255940 TI - Dermatologic surgery--its scope and some practical aspects. AB - Dermatologic surgery is of increasing interest to both dermatologists and other medical practitioners. It includes procedure like biopsy, excisional surgery, laser surgery, electrosurgery, curettage surgery, nail surgery, cryosurgery, minigrafting, sclerotherapy, collagen implant, punch grafting, Moh's micrographic surgery, dermabrasion and hair transplant. This article highlights the important aspects of the various procedures and some of the more important practical points. PMID- 2255941 TI - Importance of measurement of bone density in the management of osteoporosis. AB - Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include radiogrammetry (RG) and radiographic photodensitometry (RD), single and dual photon absorptiometry (SPA and DPA), quantitative computed tomography (QCT), and single and dual-energy X ray absorptiometry (SEXA and DEXA). These techniques provide bone mass quantitation at the spine, wrist, hip and total body skeletal sites that are the principal areas usually involved in osteoporosis. The evaluation of the aetiology, progression, and treatment of osteoporosis has been clearly improved with the use of these methods. It is the intent of this review to discuss the pros and cons of these techniques, in particular their applications to the detection and management of osteoporosis. PMID- 2255942 TI - Sleep apnoea presenting as severe hypertension and silent occipital haemorrhage. AB - A 39-year old Chinese man presented with an acute onset of severe headache, accelerated hypertension and subsequently an unexpected extensive right occipital haemorrhage. These were found to be related to a sleep apnoea syndrome which had been unrecognized for many years despite its typical symptoms of loud snoring and excessive daytime sleepiness. Weight reduction led to significant clinical but not polysomnographic improvement of the sleep apnoea syndrome. PMID- 2255943 TI - Narcolepsy in a young Chinese child. AB - Narcolepsy is characterized by narcoleptic sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations. It is very rare in children. A 7-year old Chinese boy presenting with typical narcoleptic symptoms is reported. Diagnosis of narcolepsy usually relies on the clinical picture, the presence of sleep-onset REM periods on nocturnal polysomnograph and the Multiple Sleep Latency Test. The strong association with HLA-DR2 may help in diagnosis, especially in children. PMID- 2255944 TI - Magnetic resonance imaging of peripheral soft tissue hemangiomas. AB - Ten patients with soft tissue hemangiomas outside the central nervous system were studied with MR imaging. Eight patients were studied at 1.5 Tesla (T) with T1 weighted and triple echo T2-weighted sequences. Two additional patients were imaged on a 0.5-T system. The MR images were correlated with images from other modalities. Histologic diagnosis was obtained in all cases. It was found that prolonged T2-weighted imaging together with standard spin echo T1 and T2 pulse sequences is a good substitute for contrast-enhanced CT and arteriographic evaluation of soft tissue hemangiomas. PMID- 2255945 TI - Destructive spondyloarthropathy and radiographic follow-up in hemodialysis patients. AB - Nine patients undergoing regular dialytic treatment for more than 60 months showed clinical and radiologic features of a noninfective and destructive spondyloarthropathy. The cervical spine was most affected (100%), followed by the dorsal (three patients, 33.3%) and the lumbar spine (two patients, 22.2%). Typically, radiographs and CT scans revealed narrowing of intervertebral spaces, with destruction or sclerosis of the subchondral bone of the vertebral plate. Autopsy was performed on three patients; histologic study demonstrated the presence of large amyloid deposits containing beta 2-microglobulin (beta 2-m) in the discs and peridiscal ligaments. A radiographic follow-up of the cervical spine was performed in seven patients after a period of 12 months and showed that the bone destruction in DSA is very rapid and progressive. The lower biocompatibility of the cuprophan membranes of dialyzers is probably the factor most responsible for hyperproduction of beta 2-m and subsequently osteoarticular deposition of a new type of amyloidosis. PMID- 2255946 TI - Magnetic resonance appearance of sacral insufficiency fractures. AB - Insufficiency fractures of the sacrum are a commonly recognized form of stress fracture typically occurring in elderly patients. As such patients usually present with low back pain, MR imaging is often performed initially as a means of evaluation. We present 5 patients with sacral insufficiency fractures imaged with MR. Metastatic disease was a leading clinical suspicion as all patients were elderly and three had known primary neoplasms. T1-weighted sequences demonstrated bands of decreased signal intensity, usually paralleling the sacral aspect of the sacroiliac joints and occasionally occurring as a horizontal band across the sacral body. Four of five patients underwent further evaluation with computed tomography (CT) or nuclear bone scanning, which confirmed the diagnosis of sacral insufficiency fracture. We conclude that MRI is sensitive but not specific in detecting sacral insufficiency fractures. As MR imaging is rapidly becoming the method of choice for evaluating back pain, it is important to consider this diagnosis in elderly persons. PMID- 2255947 TI - Magnetic resonance appearance of fibromatosis. A report of 14 cases and review of the literature. AB - We reviewed retrospectively the magnetic resonance (MR) images of 14 soft-tissue lesions of fibromatosis (desmoid tumors) encountered in 11 patients. The lesions were typically inhomogeneous in texture and round to oval in configuration. Margins were well-defined in 78% of the lesions at presentation and were infiltrating in all recurrences. On T1-weighted spin echo MR images, the predominant signal intensity was either isointense or minimally hyperintense when compared with skeletal muscle. On T2-weighted MR images the predominant signal intensity was typically intermediate between skeletal muscle and subcutaneous fat or isointense to fat. Linear and curvilinear areas of decreased signal intensity were distributed throughout the lesions on both pulse sequences in 86% of cases. This pattern strongly suggested fibromatosis. Speculation concerning possible etiologies of this appearance are discussed, and the relevant literature on previously reported cases is reviewed. PMID- 2255948 TI - Magnetic resonance imaging of musculoaponeurotic fibromatosis. AB - Musculoaponeurotic fibromatosis can be mistaken for soft-tissue sarcoma both clinically and on X-ray computed tomography. Magnetic resonance imaging (MRI) in three patients with this condition enabled the correct diagnosis to be made prospectively in two. The appearance on MRI of a heterogeneous mass with well defined, predominantly peripheral areas of very low signal intensity due to dense fibrous tissue and areas of medium to high signal intensity corresponding to a more cellular stroma should raise the the suspicion of musculoaponeurotic fibromatosis. Cellular areas within the tumour showed moderate enhancement after gadolinium diethylene triamine pentaacetic acid administration. PMID- 2255949 TI - Growth plate injury of the hand and wrist in renal osteodystrophy. AB - We present two cases of growth plate injury of the hand and wrist in young patients with renal rickets and osteodystrophy but no history of antecedent trauma. The postulated mechanism of injury is subclinical biomechanical stress on the involved extremity superimposed on the already weakened metaphysis and growth plate. Thus, the findings may be viewed as an insufficiency injury to the metaphysis and growth plate. Physicians should be aware that, in the absence of unusual athletic activity, epiphysiolysis of the upper extremity is uncommon and requires a search for underlying metabolic bone disease. PMID- 2255950 TI - The unilateral wavy clavicle. AB - 14 patients are recorded in whom one clavicle has a wavy shape not related to trauma or to a known congenital anomaly. Since the affected clavicle is more often the right, it is suggested that this alteration may be related to the effect of subclavian artery pulsations, such as cause congenial pseudarthrosis of the clavicle. PMID- 2255951 TI - Cervical spine flexion patterns. AB - Lateral projection flexion and extension radiographs of the cervical spine are stress views. They are necessary to evaluate unstable ligamentous injury, which may not be apparent on neutral unstressed films. As there is very little literature on the proper evaluation of these radiographic views, we reviewed 150 consecutive cases from our Emergency Department to define patterns of flexion. Four significantly different patterns emerged. No flexion at any level was seen in 24.7% of patients. A single flexion angle was seen in 24.7% Two flexion angles, usually at consecutive levels, were present in 29.3% of patients, and 21.3% had three or more flexion angles. Correlation with clinical data suggests that attempted flexion with no significant angle or a single angle is abnormal and may indicate soft tissue (ligament or muscle) injury. Three or more flexion angles are thought to represent a normal pattern. The most common pattern, two flexion angles at consecutive levels, has not been previously described. We believe this pattern indicates less than full flexion and can be seen in individuals without significant injury and in those limited by mild soft-tissue injury. PMID- 2255952 TI - Case report 633. Posterior dislocation of the long head of the biceps tendon without fracture of the tuberosity. PMID- 2255953 TI - Case report 634. Osteosarcomatosis. PMID- 2255955 TI - Case report 636. Tetrapolysyndactyly with postaxial type of polydactyly. PMID- 2255954 TI - Case report 635. Chondroblastoma of the fourth metatarsal bone with secondary aneurysmal bone cyst. PMID- 2255957 TI - Case report 638. Chondromyxoid fibroma of a sesamoid bone. PMID- 2255956 TI - Case report 637. Mixed type liposarcoma with myxoid and pleomorphic patterns. PMID- 2255958 TI - Associations with life satisfaction among very elderly people living in a deprived part of inner London. AB - In the present study 662 people, aged 85 and over, living at home in a socially deprived part of the east end of London were interviewed in order to ascertain their life circumstances, emotional well-being, mental and physical health status. The aim of the analyses presented here was to determine the impact of social networks and support, functional status and reported morbidity on life satisfaction. Multiple regression analysis showed that physical health status was a stronger predictor of emotional well-being in relation to life satisfaction than social network characteristics. The uniqueness of the study lies in its concentration on a very elderly age group, predominantly in the lower socio economic classes. PMID- 2255959 TI - Stress experienced by physicians and nurses in the cancer ward. AB - This study examined occupational stress amongst medical staff on cancer wards. The sample consisted of 91 nurses and 57 physicians from 13 institutions in Bavaria, F.R.G. Strong associations emerged between specific, situational stressors and reported psychosomatic complaints. In particular, interpersonal difficulties, whether on or off the job, related to physical distress amongst nurses. For doctors, dissatifaction with the job and working conditions related to general malaise. Certain characteristics of the carer (sex, profession, age) and of the institutional environment (e.g. presence of trainees, size of institution) were also linked with stress and complaint levels. PMID- 2255960 TI - Condoms and cosmology: the 'fractal' person and sexual risk in Rwanda. AB - While condoms are readily available in the urban centers of Rwanda, where the AIDS epidemic has ranged most intensely, researchers report that women are reluctant to have their partners use them. When asked to explain their reluctance, these women express the fear (along with other misgivings) that the condom might remain lodged in the vagina after intercourse. This behavior flies in the face of the biomedical assessment of risk. Rwandans, however, perceive risk in a manner which is consistent with their views concerning the social construction of the moral person. Of prime importance in this process is the body's perceived aptitude to engage in meaningful exchange and fertile sexuality. Moreover, these notions take root within a coherent cosmological matrix which emphasizes the socially ordered flow of fertility fluids. Only when these issues are considered in light of the concept of the 'fractal person' does the meaning of risk--as it relates to sexual behavior and AIDS in Rwanda--become clear. PMID- 2255961 TI - Health, attitudes and beliefs of working women. AB - A cross-sectional case-control study was conducted comparing working women employed by the Women's Work Centres of the Orangi Pilot Project with non-working matched controls. Differences in the knowledge, attitude and practice of several variables were elicited. Working women's families had significantly higher immunization rates, 73% vs 55%, and shorter duration of illness, 5.9 days vs 8.8 days, compared to controls. More working than non-working women supported contraception, 100% vs 74%, desired equal education for sons and daughters (P less than 0.005), and had a dominant role in family health decision-making, 48% vs 12%. We conclude that these working women in Orangi have a different set of beliefs and practices than non-working women and this may be one important factor responsible for the lower morbidity in their children. PMID- 2255962 TI - Patterns of psychosocial performance in the doctor-patient encounter: a study of family practice residents. AB - Doctor-patient psychosocial interactions were studied for a group of 34 family practice residents. Analysis of the data of 102 patient encounters indicated that a continuum of psychosocial skills existed, with residents exhibiting generally strong performance in certain areas, and generally weak performance in others. Specifically, residents appeared more competent with basic psychosocial interactions than with those requiring a more in-depth encounter with the patient's phenomenological reality. Differences by year of resident were noted, with third year residents generally performing better in areas requiring more complex and intimate interactions. Differences according to sex of resident were also observed, with women residents outperforming male residents in many of the more complex areas of psychosocial interaction. PMID- 2255963 TI - Towards rational medicine use: is there a role for children? AB - Irrational, wasteful, and even dangerous medicine use is a serious problem in developing countries. It is important to work to solve it through the provision of safe, efficacious and affordable drugs, through strengthening the drug regulatory systems and through the education of health care providers. However, it is important as well that the population learns to use medicines wisely. Educating children in developing countries about appropriate use of medicines is a strategy that has the potential to improve medicine use throughout the communities where the children live and for future generations. Currently, very few children's health education curricula include anything on appropriate medicine use, and what exists has not been based on what children know, or on their behavior or expectations relative to medicines in the context of their cultures. Support is sought for the inclusion of rational medicine use in comprehensive school health curricula and researchers are encouraged to develop and evaluate culturally sensitive, age appropriate, and acceptable medicine use education programs. PMID- 2255964 TI - Some health dimensions of self-efficacy: analysis of theoretical specificity. AB - Based on data drawn from a random-digit-dial probability sample of adults in a major American metropolitan area, this study supports the perspective that self efficacy is domain specific and that outcome efficacy is distinct from self efficacy. Data were collected by telephone interviewers which were administered by telephone interviews to 525 respondents with a 64.1% completion rate. Sample demographic summary statistics closely approximated population parameters. Five orthogonal factors emerged from analysis of self-efficacy and outcome efficacy items. The five factors represented self-efficacy with regard to nutrition, medical care, exercise, and with a set of neutral control items relating to political behavior, and with the outcome efficacy items for each behavioral domain. Hypotheses relating scores for each factor with a number of behavioral indicators were tested. Only four of 125 correlations failed to support hypothesized relationships, lending evidence for the discriminant validity of the self-efficacy dimensions. PMID- 2255965 TI - Expanding theoretical conceptualizations of self-help groups. AB - Self-help groups, a prevalent and significant source of social support, manifest the public-participation premise of primary health care. Yet, self-help studies have typically lacked theoretical grounding. Psychoneuroimmunological and social learning theories could contribute to the theoretical understanding of self-help groups. As self-help groups can mitigate the impact of natural social-network losses, they could help prevent health disorders via an immunocompetence maintenance function. Health professionals could consider this possibility in assessment, planning, intervention and evaluation. Furthermore, health professionals could take steps to enhance self-efficacy and collective efficacy, derivative concepts of social-learning theory germane to self-help groups. Therefore, pertinent concepts and creative linkages are proposed in a preliminary attempt to initiate a self-help group theoretical framework for health professionals. PMID- 2255966 TI - Cooperation in mental health: an Italian project in Nicaragua. AB - The experience acquired over the last four years in developing a program of cooperation in mental health in Nicaragua is reported. The concept of 'transfer' underlying the intervention and the general framework of Nicaragua's mental health system is discussed together with the results of the cooperative work. This included organizing training for mental health workers in six teaching and supervision modules, drawing up a mental health manual for primary health care workers, and survey of patterns of care in the 15 existing psychiatric services. Besides the key aspects of general reform of the psychiatric system after the revolution, the paper focuses on differences between organization and patterns of care in urban and rural areas. PMID- 2255967 TI - International behavioral responses to a health hazard: AIDS. AB - This paper expands on Jonathan Mann's third wave of the AIDS pandemic: the epidemic of economic, social, political, and cultural reaction and response to the HIV infection and to AIDS. This worldwide epidemic is a major economic challenge, especially in Third World countries, which can ill afford additional health care costs. AIDS is also a harbinger of political and cultural conflicts between and among nations, states, institutions, and people everywhere. It may ultimately transform law as radically as it has health care practices. In terms of management, it is possible to approach AIDS much as we do natural and technological hazards. The biology and epidemiology of AIDS require a coordinated attack, involving research on vaccines and drugs, modification of human behavior and education of populations to arrest the disease. All of these require money, of which the United States was the major contributor before the Reagan years. Funding to the United Nations and WHO has since languished, jeopardizing the AIDS efforts of those two organizations. PMID- 2255968 TI - Self-perceived health among sports participants and non-sports participants. AB - This paper examines and compares the self-perceived health (SPH) of a sample of sports participants (n = 1385) and a matched sample of non-participants (n = 292). Ratings of health were generally found to be favourable among both samples, but a non-parametric analysis of their distributions revealed that the SPH of sports participants was significantly (P less than 0.0001) better than that of the non-participants. SPH improved with age among both samples, but above the age of 34, the non-participants' perceived health ceased to be inferior to that of participants. Controlling for age and gender revealed no difference in SPH above 24 years among males and 34 years among females. SPH was related to a variety of additional health-related factors. Multiple regression analysis was used to identify the predictors of SPH for both samples, and highlighted marked differences between them in the type and number of contributory factors. It is suggested that participation in active sports may enhance health awareness, especially among the young, and that future studies of this kind among sports populations should take account of the levels of commitment (frequency, duration and intensity) to sport. PMID- 2255969 TI - Gender, employment and medication use. AB - Analyses using self reports and medical and pharmacy records of 762 men and women were conducted to assess the impact of general health status, health factors related to women's reproductive role and employment status on their use of over the counter and prescription drugs. Results showed that factors related to general health status and women's reproductive role are major contributors to gender differences in drug use. Employment is associated with a lower incidence and prevalence of drug use for men, but not for women, and the patterns of over the counter and prescription drug use are differentially affected by employment status, gender and health status variables. PMID- 2255970 TI - Oral rehydration therapy and social marketing in rural Kenya. AB - In just a few years, oral rehydration therapy (ORT) has become the standard treatment to reduce infant diarrhoeal disease mortality in the developing world. The paper describes an ORT intervention campaign in a rural area in Western Kenya (Kakamega District). After about a year of careful preparation, the campaign was launched in January 1986 and compared the use of a value-added product (flavoured sachets) sold through private outlets in addition to primary care distribution of an unflavoured sachet in an experimental cell (Bukura Division). In a control cell (Novakholo Division), only unflavoured sachets were distributed free of charge through primary health care facilities. Using local perceptions of diarrhoeal disease management, the campaign in the experimental cell was carefully designed and mass communication techniques employed and adapted accordingly. Outcome assessments of the campaign, which lasted until March 1987, included the overall ORT utilisation over time. Changes in perceptions towards diarrhoeal disease management, direct assessments of mixing a 'safe and effective' solution accurately and other relevant process parameters were evaluated. Comparing several recent ORT intervention projects, the paper concludes that a combination of a commercial approach and mass communication techniques can further ORS use. If a proper incentive system for shopkeepers is installed and message design and ORS product are fully tailored to the perception and preferences of the target population, the commercial availability of ORS will create an extra demand of the product. However, this will not replace distribution of ORS salts delivered free of charge through primary care sources. PMID- 2255972 TI - Do attitudes predict uptake of smoking in teenagers? Case not proven. AB - A recent paper by Charlton and Blair (Soc. Sci. Med. 29, 813-818, 1989) reported a large prospective study on smoking in 12 and 13 year-old schoolchildren. The main new findings were that attitudes, particularly among girls, were important predictors of the uptake of smoking in never-smokers. The present paper presents a critique of this study and argues that the findings may not reflect true predictive relationships. Data are presented from OPCS-conducted national surveys which indicate that a substantial minority of children who initially classify themselves as never-smokers admit to having tried a cigarette when prompted. These undisclosed triers differ from confirmed never-smokers on relevant predictor variables, and are significantly more likely to agree that they will try a cigarette again before leaving school (12% vs 4%, P less than 0.005). A similar group would be expected in Charlton and Blair's study and might wholly or partially account for the apparent predictive relationships found. This is first because such undisclosed triers might be more accurate in their self-reports when questioned a second time, but also because this group would contribute disproportionately to those trying smoking in the follow-up period. Other issues raised concern the homogeneity of the attitude variables employed, and the difficulty of attributing any specific importance to particular attitude items. PMID- 2255971 TI - An orientation toward help-seeking for emotional problems. AB - In recent years, many researchers tried to explain the social selection in use of mental health care services. A modest role is attributed to the orientation toward help-seeking. This article studies this orientation. Our research population consisted of 10,171 Dutch persons, aged 18 and older. Analysis showed that most people are prone to seek help for one or more emotional problems. People who are more prone to seek help are younger, have had more education and have a higher family income. They have more often acquaintances working in mental health care. People who are more prone to seek help do not see chance as the locus of control of health. These people are less dependent on their GP for common disorders and are more open about mental health matters. The results of discriminant analysis are not satisfactory, but when we try to distinguish the groups of people who are and who are not willing to seek help, we see that the best discriminating factor is their help-seeking attitude for common disorders. People who have high expectations from the GP for common disorders, clearly do have a preference to seek help for the emotional problems. The groups of people who are more willing to seek help from the GP compared to mental health professionals cannot be distinguished by these expectations. Here the level of education discriminates fairly well: people who are more prone to seek help from a GP have a lower educational level. Future research should be focussed on the testing of a theoretical model that explains the orientation toward help-seeking for emotional problems and selection in help-seeking with longitudinal data. PMID- 2255973 TI - [Evaluation of the technology of health care delivery under new economics]. AB - The development and improvement of technology in health care delivery and its utilization in applied public health is a prerequisite for improving the quality of curative and diagnostic process, rational use of material and technical resources and medical personnel of curative and preventive establishments under new economic methods of public health management. The volume standards of health care delivery comprising the standard, optimum sets of measures for patients including the list of diagnostic and treatment procedures can be considered as the main instrument and the major criteria in evaluating the completeness and quality of health care delivery at hospital stage and at different regional levels. PMID- 2255974 TI - [The degree of the satisfaction of population with activities of the district physician]. AB - Within the limits of the study undertaken by WHO Regional Office for Europe population's satisfaction of district physician's performance was assessed. 516 adult inhabitants of a big city were interviewed using the adapted variant of the questionnaire. As a result a desired by the population model of personal and professional qualities of this most popular public health figure was created. The work done indicates the advisability of using sociological surveys as one of the criteria of health care delivery for the population. PMID- 2255975 TI - [Evaluation by the population of health care delivery in an urban polyclinic]. AB - The findings of investigating the possibilities of managing the quality of health care delivery in an urban polyclinic are provided on the basis of studying the patient's satisfaction of the care delivered. The materials are addressed to physicians and senior staff of urban polyclinics. PMID- 2255976 TI - [Bed occupancy in emergency hospitalization of patients]. AB - When planning the average number of bed occupancy days per year at a hospital providing emergency hospitalization one should take into account the demurrage of reserve beds which are needed for urgent hospitalization of patients. The influence of emergency demurrage of reserve beds on occupancy rate is not determined by the absolute number of these beds and their share in the structure of hospital bed fund. The number of reserve beds depends on the number of emergency patients hospitalized and the average length of hospital stay. PMID- 2255977 TI - [Activities of consultative and diagnostic polyclinics and centers in Moscow]. AB - The article provides an evaluation of activities of consulting and diagnostic centres (CDC) which operate on the basis of Moscow multi-disciplinary hospitals. The existence of CDC oriented towards secondary (after screening at polyclinics and according to their referrals) screening of patients in accordance with in depth programme and provision of consultations is justified and permits to raise the quality of medical care for the population. PMID- 2255978 TI - [Team form of the organization and payment for work in stomatological services]. AB - The article describes a new approach to solving the problem of raising the effectiveness of specialists' labour primarily through the new organization of work and strengthening the stimulating role of individual and team performance related pay in order to improve the quality of curative work and to achieve stable results of treatment both for the nearest and more distant future. For this purpose the author reveals the essence and operational mechanism of the new form of organization and stimulation of stomatologists' labour, makes recommendations on conduction of preparatory activities and establishment of adequate conditions for successful and effective performance. PMID- 2255979 TI - [Democracy, inequality and health]. PMID- 2255980 TI - [Evaluation of the methods of analysis of diagnostic errors]. AB - The article provides a critical analysis of validity of existing modifications in the methods of evaluating the quality of diagnosis (E. E. Ben, E. R. Guglina, N. S. Sokolova et al, M. N. Petrov). The authors suggest a technology for calculating the indices of diagnosis quality adapted for applied public health and consisting of five consecutive operations. A new additional indicator of comprehensive polyclinic diagnosis (P) is introduced--the ratio (in %) of the number of diagnoses made by the polyclinic and confirmed by the hospital to the general number of diagnoses made by the hospital. PMID- 2255981 TI - [Evaluation of the effectiveness of work of medical personnel]. AB - Methods for expert evaluation of physicians' labour are suggested which provide recommendations on physician's category and performance pay, a suggestion is also made of methods for sociometric study identifying informal structure of the collective. Heads of subunit, informal leaders and clinical workers from chairs of medical institute are also engaged in expert evaluations. Unbiased attitude towards evaluation is controlled by correlation analysis. Socio-psychological characteristics of leaders are provided, coefficient of their managerial skills is determined. The results of studying the qualification level of physicians from central regional hospital N 4 of the city of Kiev are discussed. PMID- 2255982 TI - [Improvement in the control of results in departments of medical institutes]. PMID- 2255983 TI - [Methods of evaluating levels of pathology according to the trimester of pregnancy]. PMID- 2255985 TI - [Emil Evgenii Resle (1875-1962)]. PMID- 2255984 TI - [Characteristics of medical-social care organization in the Finnish Republic]. PMID- 2255986 TI - [V. O. Merzheevskii--the founder of national forensic gynecology]. PMID- 2255987 TI - [Natural science views of Russian physicians of the 17th century]. PMID- 2255988 TI - [The first congress of district physicians of the Vyatka province]. PMID- 2255990 TI - Dental students' views on their education and study circumstances in Nordic countries. AB - The curricula at the Nordic dental schools are similar in their content but may vary in the placement of different subjects and the way of teaching them. The aim of this study was to analyse Nordic dental students social background, and their reasons for choosing dentistry, their opinions on the course, and their future professional plans. A combination of an open-ended and structured questionnaire was given to final year dental students at the dental schools in Aarhus, Bergen, Kuopio and Stockholm. The response rate as 83%. The main reasons for choosing dentistry were its combination of theory and practice (29%), and a wish to work with people (20%), whereas only 4% mentioned the "high status" of the profession. Regular day-time work was emphasized by female students. Most students considered the teaching load heavy. The time devoted to the different subjects was considered sufficient, except for behavioural science and medicine, where the time was too short. There was general dissatisfaction with the teachers pedagogical skills, and there was a feeling that teaching was regarded as secondary to research. Most students planned to become private practitioners. Between 25-55% of the students wanted to specialize, and oral surgery was the most popular specialization. PMID- 2255989 TI - Class II composite resin restorations: a three-year clinical study of six different posterior composites. AB - Class II restorations of five light-cured posterior composite materials (Occlusion, P 30, Fulfil, Profile and Heliomolar) were followed for three years, and restorations of another material (Distalite) were followed for two years. Twenty-four dentists from The Public Dental Health Service in the county of Bohuslan placed 242 Class II restorations in 213 patients. The restorations were evaluated after three years using the USPHS criteria. Stone casts were used to categorize quantitatively the amount of occlusal wear according to the Leinfelder method. No differences could be found between the different materials regarding clinical properties. The failure rate (USPHS ratings Charlie) was low, 6.5 per cent. The average occlusal wear after three years for most of the materials was about 100 micrometers. Heliomolar showed a better resistance to wear compared with the other materials. PMID- 2255991 TI - Correlation between caries incidence and secretion rate/buffer capacity of stimulated whole saliva in 5-7-year-old children matched for lactobacillus count and gingival state. AB - The correlation between caries incidence and secretion rate/buffer capacity of stimulated whole saliva was studied in 87 children over the period from 5 to 7 years of age. Coefficients of correlation were calculated in subgroups homogenized with regard to lactobacillus count and gingival state. The highest value for saliva secretion rate was found in the subgroup with favourable values of the factors used for matching (r = 0.07). For buffer capacity the highest value was found in the corresponding subgroup (r = -0.31). The caries differences between groups with less favourable and favourable values of the salivary variables were also determined after elimination of the modifying effects of lactobacillus count and gingival state. The percentage difference varied between 20 and 26. It was concluded that the saliva secretion rate and buffer capacity of saliva have a weak connection with caries incidence at this age. PMID- 2255992 TI - Use of gloves among dentists in Sweden. AB - This study among 191 public and private dentists in the Malmohus County of southern Sweden showed that 77% of the community dentists (n = 167) and 54% of the private dentists (n = 24) used gloves regularly as infection precaution during extraction. For surgery these figures were 90% and 54% respectively. These were low figures considering the several general recommendations from both the Swedish National Board of Health and Welfare and local community authorities to dental personnel to use gloves regularly during procedures with known risk of blood contact. The survey showed that 61% (n = 167) of the public dentists and 4% (n = 24) of the private dentists used gloves regularly during all patient treatment. High cost for gloves was no major obstacle for not using them regularly but rather discomfort and old habits (79% of the answers). 21% of the dentists had experienced local infections of their hands due to patient contact, puncture wounds being the most common cause. Most of the dentists using gloves had been influenced by the general HIV/AIDS discussion in news media (65%; n = 114). PMID- 2255993 TI - Effect of early dental health education for Finnish immigrant families. AB - The aim of the study was to evaluate whether or not the dental health of Finnish immigrant children would benefit from an extra session of information to the parents at the Child Health Centre, and whether this information, to be effective, should be given in Finnish. A further aim was to study the effect of this information on the parent's dental health knowledge and behaviour. Three groups of Finnish children, two test groups (FF and FS) and one control group (FC), and one control group of Swedish children (SC) took part in the study in Norrbotten and Stockholm county respectively. When the children were 6, 18 and 27 months of age, the parents of the Finnish test groups received information, the FF-groups in Finnish, and the FS-groups in Swedish. The parents of the Finnish and Swedish control groups were informed when the children were 6 and 18 months of age in Swedish. The various programmes were evaluated by comparing prevalence of dental caries of the children at the age of 3, as well as parents' attitudes to and knowledge of dental health and dental health behaviour. In Norrbotten 71% of the children in the FF-group were caries free compared to 53% in the FS-, 30% in the FC- and 80% in the SC-groups, and dfs averaged 1.7, 2.7, 6.0 and 0.9 for the groups respectively. The percentages of caries free children in Stockholm were 71, 58, 32 and 82 for the groups respectively and the mean dfs values 1.2, 2.1, 4.6 and 0.7. The data from the 36-month appointment showed equally good dental health knowledge and behaviour for the FF-groups as for the Swedish control groups. PMID- 2255994 TI - Macroscopic, microscopic and radiologic assessment of the condylar part of the TMJ in elderly subjects. An autopsy study. AB - Thirty-seven temporomandibular joints were examined in an autopsy study. The sizes and forms of the condyles were found to be in good agreement with earlier presented results. Structural changes were found in 16 condyles (38%) in the macroscopic examination, while radiographically diagnosed erosions were found in 8 (21%). Twenty-two (59%) of the discs examined had either perforations, roughness or attenuations. Anterior disc position was found in 3 discs, and always in combination with a perforation of the disc. PMID- 2255995 TI - Periodontal healing after scaling and root planing with the Kavo Sonicflex and Titan-S sonic scalers. AB - Several types of air turbine scalers have recently been introduced as alternatives to hand instruments and ultrasonic devices in periodontal therapy. Whereas differences in scaling and root planing efficiencies have been demonstrated in vitro between different types of sonic scalers (Lie & Leknes 1985), periodontal healing after instrumentation with the Titan-S sonic scaler, Cavitron ultra sonic scalers and hand instruments has shown to be similar (Gellini et al. 1986, Loos et al. 1987, Laurell & Pettersson 1988). This split mouth designed study compared periodontal healing expressed as reduction in number of sites with probing depths of 4 mm or deeper and bleeding on probing following scaling and root planing with the Sonicflex and the Titan-S sonic scalers. Fifteen patients with moderately advanced periodontitis participated in the study. In each patient one side of the dentition was treated with the Sonicflex and the other with the Titan-S sonic scalers. Reexaminations performed three and seven months after treatment showed significant and similar reductions in number of sites with probing depths of greater than or equal to 4 mm and bleeding scores for the two sides. PMID- 2255996 TI - Reasons for replacement of Class II amalgam restorations in private practice. AB - In a series of postgraduate courses in Cariology for dentists in the period 1980 84, a total of 102 private practitioners participated in a study of the reasons for replacing amalgam restorations. Twelve reasons were specified on a form and the dentist was asked to mark one or more of them for each filling replaced. The total number of fillings evaluated was 2033. In 87.9% of the restorations only one reason was given for the replacement; two, three, four and five reasons were registered in 10.5, 1.1, 0.4 and 0.1%, respectively. The six most frequent reasons were: "secondary caries" (34.0%), "fracture of the filling" (15.5%), "primary caries" (12.1%), "fracture of the tooth" (10.2%), "marginal ditching" (7.2%), and "caries under the filling" (5.6%). The restorations replaced for a combination of two reasons (N = 213) were studied separately. The three most frequent combinations were: "secondary caries + fracture of the filling" (17.8%), "secondary caries + marginal ditching" (14.1%), and "secondary caries + caries under the filling" (11.3%). - Thus, the main conclusion from this study is that approximately half of the replacements of class II amalgam restorations were occasioned by caries disease. PMID- 2255997 TI - Dental health in 13-year-olds in Vasterbotten County, Sweden. Changes over twenty years. AB - An epidemiological study of the prevalence of dental caries and gingivitis in 13 year-olds was carried out in the county of Vasterbotten, Sweden, in 1987. Besides providing information on the dental health of this age group, prevalence data were compared with data from earlier surveys of the same age group carried out in 1967 and 1977, covering the same areas and applying the same diagnostic criteria and methods. The results showed a marked decrease in the prevalence of caries and gingivitis. The mean number of DMF surfaces was 4.6, compared to 9.0 in 1977 and 19.0 in 1967. The mean GBI% was reduced from 33% to 21% between 1977 and 1987. In contrast to the results from 1967 and 1977 the differences in mean DMF values between the three areas were nonsignificant in 1987. The decline in dental caries is most probably due to an extended regular dental care with a strong preventive approach. Only slight differences in dental health were found between the three areas in 1987 in contrast to in 1977 and 1967. The most likely reason was probably that larger resources had been allocated to preventive programmes in the rural areas than in the city of Umea. PMID- 2255998 TI - Trisomy 22 with holoprosencephaly: a clinicopathologic study. AB - Trisomy 22 (47, XY, +22) was found at 17 weeks gestation in one fetus of a twin gestation. The karyotypes of both parents and of the other twin were normal. Abnormal prenatal findings included maternal pre-eclampsia, fetal growth retardation, and progressive intracranial sonolucency of the trisomic fetus. Delivery by cesarean section at 36 weeks gestation yielded a normal healthy female weighing 2,822 grams and a markedly macerated dysmorphic male weighing 642 grams. Holoprosencephaly was found in the trisomic fetus, an unusual feature in trisomy 22. Additional findings in this case are compared to other findings in the literature. PMID- 2256000 TI - Route-dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters. AB - Inorganic selenium (Se) salts (selenite and selenate oxyanions) and the organic selenoamino acids (selenomethionine and seleniferous grains) are teratogenic and embryolethal in domestic and wild birds. Selenium bioaccumulation has been held responsible for reproductive failure among waterfowl at the Kesterson Reservoir (California), the Ouray and Stewart Lake Wildlife Refuges (Utah), and the Carson Sink (Nevada). Anecdotal field and controlled laboratory reports have implicated Se exposure in mammalian embryotoxicity (including human), but developmental toxicity studies in hamsters failed to demonstrate an adverse response, except at maternally toxic doses (Ferm et al., Reprod. Toxicol., in press). Uptake, distribution, and elimination of Se after a single bolus equimolar dose (60 mumol/kg) of selenate or selenomethionine by oral or intravenous administration were compared using day 8 pregnant hamsters. Intravenous selenate was eliminated ten times more rapidly from maternal plasma than oral selenate, but concentrated in liver, kidney, and placenta to the same degree. Intravenous (iv) L selenomethionine achieved lower maximum circulating total [Se], but it was eliminated more slowly than iv selenate. Larger areas under the plasma and peripheral tissue [Se]:time curve (AUC) after oral or parenteral selenomethionine than after equimolar selenate were consistent with previous studies in rodents and in humans. Embryonic [Se] plateaued at 3 nmol/g after selenate, but embryonic [Se] after selenomethionine continued to accumulate (80 nmol/g) as gestation progressed. The lack of a teratogenic response in hamsters at doses of either selenate or selenomethionine less than those associated with maternal intoxication cannot be attributed to lack of Se accumulation in early embryonic and placental tissue. PMID- 2255999 TI - An anatomic comparison of cebocephaly and ethmocephaly. AB - Cebocephaly (hypotelorism, single-nostril nose) and ethmocephaly (hypotelorism, interorbital proboscis) lie in the middle of the spectrum of craniofacial changes associated with holoprosencephaly. Because these defects and thorough anatomic studies of them are rare, knowledge concerning morphologic as well as pathogenetic relationships is lacking. We report the autopsy findings and anatomic features of the dried skull of a 31 week fetus with cebocephaly and the craniofacial dissection of a 36 week fetus with ethmocephaly. Both manifested dysplastic changes of the ethmoid bone and anterior portion of the sphenoid bone, with concomitant hypotelorism and defects of the medial orbital walls. Through these latter defects, the eyes were joined in the ethmocephalic fetus (synophthalmia). Other changes of bone (single optic foramen, approximated maxillae, choanal atresia, thickened palate) and soft tissue (eccentric or fused extraocular muscles, single optic nerve) in both fetuses resembled those reported in other cases of cebocephaly and ethmocephaly, as well as cyclopia. In the 19th century, both cebocephaly and ethmocephaly were classified as two-orbit variants of cyclopia, a view supported by the present study. PMID- 2256001 TI - Effect of prenatal N2O exposure on startle reflex reactivity. AB - The teratogenic effect of N2O is of interest because thousands of pregnant women are exposed to this gaseous anesthetic each year. The effects of repeated N2O exposures were investigated for offspring of mice exposed to air or N2O (5%, 15%, or 35%) for 4 hours per day on days 6 through 15 of pregnancy. Ten litters per exposure group were studied. Exposures did not affect reproductive indices, survival, or physical milestones of development. Body weights showed significant exposure effects that could not be isolated to specific exposure groups; however, N2O-exposed mice tended to weigh more than air-exposed animals. Brain weights measured on postnatal day (PND) 126 or 127 were not different among exposure groups or between genders. Ability to stay on a rotating rod was not affected by prenatal N2O exposure. Prenatal exposure to N2O resulted in hyporeactivity of the startle reflex in response to acoustic or tactile stimuli. On PND 95 the results were statistically significant for all N2O-exposed groups compared with the air exposed group. On PND 60, although not statistically significant, there was a definite trend toward hyporeactivity for the N2O groups. There was a significant age-related difference in startle response; control animals were significantly more reactive at 95 than at 60 days of age. Of the N2O-exposed groups, only the 15% group showed a statistically significant increase in reactivity from 60 to 95 days of age. The risk of behavioral or functional abnormalities for humans following in utero N2O exposure is unknown and cannot be directly extrapolated from the present study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256002 TI - Renal agenesis and dysgenesis: are they increasing? AB - Data from the Birth Defects Monitoring Program (BDMP) of the Centers for Disease Control (CDC) suggest that the birth prevalence of renal agenesis and dysgenesis combined is increasing. Medical records were reviewed for 1,404 of 1,669 (84%) infants in the BDMP with renal agenesis or dysgenesis noted on the newborn discharge summary to assess whether the observed trend reflects a true increase in one or both conditions or if it reflects changes in diagnostic, coding, or surveillance practices over time. For 1970-1982, the average rate per 100,000 live births and stillbirths was 3.5 for autopsy-confirmed bilateral renal agenesis and 1.7 for autopsy-confirmed bilateral renal dysgenesis. The birth prevalence of autopsy-confirmed bilateral renal agenesis fluctuated within this time period, peaking in 1975, while the rate of autopsy-confirmed bilateral renal dysgenesis increased steadily by 0.2 cases/100,000 births per year (P less than 0.001) with small peaks in 1976 and 1979. Unilateral renal agenesis or dysgenesis accounted for 17% of the confirmed cases, but most were detected by autopsy among infants who died shortly after birth rather than by diagnostic procedures such as ultrasound. Diagnostic information in the medical record suggested that the increase in the birth prevalence of renal agenesis and dysgenesis combined in the BDMF is due primary to the increasing prevalence of renal dysgenesis. Since medical records did not include sufficient information on risk factors, detailed analytic studies are needed to identify maternal risk factors that might account for the apparent increase in renal dysgenesis over time. PMID- 2256003 TI - Fallacies of international and national comparisons of disease occurrence in the epidemiology of neural tube defects. AB - Despite extensive research, little progress has been made in elucidating the etiologies of anencephalus and spina bifida. International and national distributions of disease occurrence have often been used as a basis for generating etiological hypotheses (e.g., potato blight, tea consumption, and zinc deficiency hypotheses). However, few of the epidemiological studies of neural tube defects (NTDs) have been conducted with scientific rigor in design, and most are of dubious validity, often with low precision in the estimates. This paper shows that the accepted geographic patterns of NTDs may be attributable to variations in the validity of studies used to describe these patterns. The nonuniformity in the duration and diligence of case ascertainment, the lack of a standardized nomenclature and classification, and the definition of the denominator remain principal problems in evaluating the epidemiology of NTDs. For example, the distinction between incidence and prevalence is not always made, and there is no consistency in the placement of the gestational boundary between late fetal deaths and spontaneous abortions. Findings are compared from studies conducted at different times, without due regard to the effect of secular trends, and using studies that have varying levels of case ascertainment. In etiological research, it is important to perform studies that are accurate and precise, but the literature used to define the spatial distribution of NTDs has often been accepted without due regard to the effect of these factors. PMID- 2256004 TI - Exposure of the pregnant rat to warfarin and vitamin K1: an animal model of intraventricular hemorrhage in the fetus. AB - Pregnant Sprague-Dawley rats were given daily oral doses of sodium warfarin (100 mg/kg) and concurrent intramuscular injections of vitamin K1 (10 mg/kg). This dosing regimen did not have any apparent deleterious effect on the dams and did not affect the fetuses when administered from day 1 to day 12 of pregnancy. However, similar treatment from day 9 to 20 caused hemorrhage in the fetuses examined on day 21 of gestation. There were no hemorrhages in the control fetuses from dams receiving vitamin K1 only. The lowest effective dose of warfarin, in conjunction with daily doses of vitamin K1, was 3 mg/kg. This dose caused hemorrhage in 28% of fetuses; the incidence of affected fetuses was not further increased by doses of warfarin up to 100 mg/kg. Hemorrhages affected the fetal brain, face, eyes, and ear and occasionally the limbs. Brain hemorrhages were frequently intraventricular and caused various degrees of hydrocephaly. Bony defects were not a feature of prenatal exposure to warfarin. These results show that prenatal exposure of the rat to warfarin and vitamin K duplicates the hemorrhagic abnormalities and pathology associated with prenatal exposure to warfarin in the human. It did not induce bony or facial defects probably because the vitamin K-dependent components of bone development occur postnatally in the rat. This model should allow detailed determination of the role of vitamin K dependent proteins in development. PMID- 2256005 TI - Immunological factors responsible for pathogenetic cell degeneration in pregnancy. AB - The placenta has an important role as an immunological barrier during pregnancy. When the placental barrier is disrupted, materno-embryonic transfusion takes place. Several clinical reports relate congenital malformations or abortion to intrauterine bleeding or transplacental transfusion. In an earlier experiment, pathogenetic cell degeneration was induced using an in vitro whole rat embryo culture. Transplacental transfusion was simulated by intracardiac injection of an allogeneic rat-antirat serum directed against the blood group antigens. The present study examines the morphological and immunological effects on the development of rat embryos 9 to 10 days old (stages 8-10 somites) of the separate administration of primary allogeneic antisera, obtained 10-17 days after immunization, and secondary allogeneic antisera, obtained after booster immunization on day 45-52. Rat-antirat alloantibodies were directed against the blood group antigens. Transplacental transfusion was simulated by the embryonic intracardiac microinjection of approximately 0.5 microliters serum enriched with either primary or secondary obtained allogeneic antibodies. After 48 hours' incubation, the embryos were examined microscopically, and it appeared that the secondary antisera, which had hemolytic activity, was more potent (P less than 0.005) in the induction of pathogenetic cell degeneration. It is well known that IgG antibodies display hemolytic activity. This finding was confirmed by direct immunofluorescence performed on rat embryos 2, 4, and 6 hours after injection, where incubation with rabbit-antirat anti-IgG antibodies gave a strong reaction. The hypothesis discussed is whether or not pathogenetic cell degeneration subsequent to transplacental transfusion of maternal antibodies can be initiated by similar immunological events. PMID- 2256006 TI - Methionine and neural tube closure in cultured rat embryos: morphological and biochemical analyses. AB - When headfold-stage rat embryos were cultured on cow serum, their neural tubes failed to close unless the serum was supplemented with methionine. Methionine deficiency did not appear to affect the ability of the neural epithelium to fuse as a type of fusion was observed between anterior and posterior regions of the open neural tube in methionine-deficient embryos. Although methionine deficiency reduced the cell density and mitotic indices of cranial mesenchyme and neural epithelial cells, this did not appear to be a factor in failure of the neural tube to close. For example, embryos cultured on diluted cow serum also had fewer mesenchymal cells yet could complete neural tube closure if provided with methionine. Examination of the tips of the neural folds suggested that microfilament contraction could be involved; in the absence of methionine the neural folds failed to turn in. This possibility was supported by the reductions in neurite extension of isolated neural tubes cultured without methionine and by the reductions in microfilament associated methylated amino acids contained in embryo neural tube proteins. PMID- 2256007 TI - Influence of some methodological factors on the radiosensitivity of the mouse zygote. AB - The experiments reported here were undertaken to investigate the influence of some methodological factors on the radiosensitivity of the mouse zygote. The following factors were studied: 1) the use of natural or hormone-stimulated ovulation; 2) the procedure followed for fertilization:mating overnight, or only during a short period in the morning after all oocytes have been ovulated, in vitro fertilization; 3) the type of irradiation, i.e., in vivo or in vitro irradiation. The radiosensitivity of the zygotes was estimated under the different experimental conditions by measuring the ability of the irradiated embryos to cleave and to develop further to the blastocyst stage. Our results suggest that the protocols used for mating and fertilization probably have a greater influence on embryonic survival following irradiation than the use of gonadotropins to stimulate ovulation. The highest degree of synchrony in the development of the embryos is achieved by restricting mating to a short period or by using in vitro fertilization. The very low LD50s obtained under such synchronous conditions confirm the high radiosensitivity of the mouse zygote at the early pronuclear stage. Comparison between the effects of in vivo and in vitro irradiation does not indicate a greater radiosensitivity of the embryo irradiated in vitro in comparison to the embryo irradiated in vivo. PMID- 2256008 TI - Exogenous surfactant treatment for the adult respiratory distress syndrome? A historical perspective. PMID- 2256010 TI - Smoking cessation in patients: two further studies by the British Thoracic Society. Research Committee of the British Thoracic Society. AB - The effects of various smoking cessation strategies were studied in two multicentre trials with new patients attending hospital or a chest clinic because of a smoking related disease. In the first trial (study A, 1462 patients) the effect of the physician's usual advice to stop smoking was compared with the effect of the same advice reinforced by a signed agreement to stop smoking by a target date within the next week, two visits by a health visitor in the first six weeks, and a series of letters of encouragement from the physician. The second trial (study B, 1392 patients) compared (1) advice only, (2) advice supplemented by a signed agreement, (3) advice supplemented by a series of letters of encouragement, and (4) advice supplemented by a signed agreement and a series of letters of encouragement. Patients were reviewed at six months and those claiming to have stopped smoking were seen again at 12 months. Claims of abstinence were checked by carboxyhaemoglobin measurement. In study A 9% of the intervention group had succeeded in stopping smoking at six months compared with 7% of the "advice only" patients (p = 0.17). In study B success rates were 5.2%, 4.9%, 8.5%, and 8.8% respectively. The signed agreement did not influence outcome, whereas postal encouragement increased the effect of the physician's advice. In both studies patients reviewed clinically between the initial and the six month visit were more likely to stop smoking than those not reviewed. Success rates increased with age and men tended to do better than women. The studies suggest that physician's advice alone will persuade 5% of outpatients with a smoking related disease to stop smoking. Subsequent postal encouragement will increase the cessation rate by more than half as much again. Such small improvements in success rates are worth while, especially if they can be achieved cheaply and on a wide scale. PMID- 2256009 TI - Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation. AB - Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing. PMID- 2256011 TI - Clearance of 99mTc DTPA from guinea pig nasal, tracheobronchial, and bronchoalveolar airways. AB - Technetium-99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) was used to compare small solute absorption (clearance) from nasal, tracheobronchial, and bronchoalveolar airways in anaesthetised guinea pigs. 99mTc DTPA dissolved in saline was superfused through nasal and orolaryngeal catheters on to nasal and tracheobronchial airways; a small particle aerosol of nebulised 99mTc DTPA was delivered to the bronchoalveolar airways through a tracheostomy. Radioactivity over the appropriate region was then determined with a gamma camera. Mucociliary transport of 99mTc DTPA appeared not to contribute to the disappearance of 99mTc DTPA. Time-activity curves were obtained and half life values calculated by fitting a monoexponential equation to the experimental data. A progressive reduction in 99mTc DTPA was recorded from the nasal and tracheobronchial airways and from the bronchoalveolar airway, suggesting that absorption was occurring. The disappearance of 99mTc DTPA was fastest from the bronchoalveolar region, which also had the largest mucosal surface. The similar shape of the retention curves for the nasal and tracheobronchial regions suggests that the characteristics of nasal absorption of 99mTc DTPA could prove applicable to the tracheobronchial region. It is proposed that the present methods are suited for comparing the pharmacology of small solute absorption across nasal, tracheobronchial, and bronchoalveolar airway mucosa. PMID- 2256013 TI - Primary bone tumours of the thoracic skeleton: an audit of the Leeds regional bone tumour registry. AB - An audit of the Leeds regional bone tumour registry found that primary bone tumours of the thoracic skeleton constituted 90 of the 2004 cases (4.5%). Thirty seven per cent occurred in the ribs, 32% in the scapulae, 11% in the thoracic vertebrae, 11% in the sternum, and 9% in the clavicles. Malignant tumours were more common than benign (54 v 36) and occurred in an older population (mean ages 47 and 31 years). The scapula was the most common site for malignant lesions and the ribs the most common site for benign tumours. Chondrosarcoma was the commonest tumour in older patients, fibrous dysplasia and plasmacytoma in the middle age group, and eosinophilic granuloma in children. Presenting symptoms were a poor guide to whether the lesion was malignant or not. This and the small proportion of correct preoperative diagnoses indicate the need for early biopsy. Bone tumour registries provide a valuable source of cumulative information about uncommon tumours and facilitate accurate diagnosis, teaching, and research. PMID- 2256012 TI - Management of post-tuberculous complex aspergilloma of the lung: role of surgical resection. AB - Of 14 patients with complex aspergilloma complicating healed tuberculosis, 12 underwent lobectomy or pneumonectomy for recurrent haemoptysis. No deaths occurred, though one patient needed re-exploration for bleeding. There was no postoperative worsening of dyspnoea despite a mean forced vital capacity (FVC) of 60% predicted for the patients undergoing surgery and of 20% predicted for two patients with severe restrictive defects, perhaps owing to the fact that there was little or no function in the resected part of the lung, as shown by preoperative isotope ventilation-perfusion scanning, and that patients were under the age of 50 and generally fit. There has been no recurrence of haemoptysis during follow up, which has been from 12 to 33 months. Surgical resection, provided that cases are carefully selected, offers the best chance of cure with low mortality and morbidity. PMID- 2256014 TI - Effect of frusemide on airway smooth muscle contractility in vitro. AB - Frusemide, an inhibitor of sodium-potassium-chloride (Na-K-Cl) cotransport, has been shown to inhibit the airway response to several constrictor stimuli in asthmatic subjects. The protection seen with frusemide in these studies could be due to an effect on epithelium, inflammatory cells, neural pathways, or airway smooth muscle. To determine whether frusemide inhibits airway smooth muscle contraction, experiments were performed in bovine and human airways in vitro. Fresh bovine tissue was obtained from the abattoir and human tissue from thoracotomy. The effect of 10(-5)M frusemide on histamine, potassium chloride, and hyperosmolar saline induced contractions was studied in bovine tracheal strips without epithelium. Frusemide, at a concentration that specifically inhibits Na-K-Cl cotransport, did not inhibit contraction caused by any of these agents. Frusemide was also without effect on hypertonic saline induced contractions of bovine and human bronchial rings with epithelium intact. These results suggest that modification of Na-K-Cl cotransport does not alter airway smooth muscle contractility and that the protective effect of frusemide on induced bronchoconstriction in vivo is unlikely to be due to a direct effect on airway smooth muscle. PMID- 2256015 TI - Bronchial hyperresponsiveness in young students of southern China: relation to respiratory symptoms, diagnosed asthma, and risk factors. AB - A cross sectional study was carried out to determine the prevalence of bronchial hyperresponsiveness and asthma in 3067 students aged 11-17 years in an urban and a rural area of Guangzhou (Canton), China. The methods used included a self administered questionnaire, a histamine bronchial provocation test, and allergen skinprick tests. Bronchial hyperresponsiveness was defined as a 20% fall in FEV1 and peak expiratory flow at a provoking dose of histamine (PD20) less than 7.8 mumol on two occasions four weeks apart. The response rate was 98.0% and 99.2% in the two areas. The prevalence of bronchial hyperresponsiveness was 4.1% and of diagnosed asthma 2.4% in the total population. There were no significant differences in prevalence between the urban and the rural area or between boys and girls. The 11-12 year group had a higher prevalence of bronchial hyperresponsiveness (7.6%) than the older groups. Of the 125 with bronchial hyperresponsiveness, 12.0% were defined as having severe or moderate (PD20 less than 0.8 mumol), 26% mild (0.9-3.2 mumol), and 62% slight bronchial hyperresponsiveness (3.3-7.8 mumol). The severity of bronchial hyperresponsiveness was closely related to diagnosed asthma, wheezing, and cough, though half the students with bronchial hyperresponsiveness were symptom free. The most common allergens were house dust and house dust mite in the city, and hay dust, pollen, and feathers in the rural area. The odds ratios for having respectively slight, mild or moderate, and severe bronchial hyperresponsiveness were 5.9, 21.0, and 30.4 for atopy; 1.9, 1.9, and 7.3 for early respiratory infection; and 3.1, 2.5, and 5.6 for a history of parental asthma. PMID- 2256016 TI - A general practice based survey of bronchial hyperresponsiveness and its relation to symptoms, sex, age, atopy, and smoking. AB - The prevalence and associations of bronchial hyperresponsiveness were investigated in a general practice population. The sample was obtained by using every 12th patient on the practice age-sex register, replacing non-responders with corresponding age and sex matched individuals from up to two further 1 in 12 samples. The response rate was 43%; 366 patients were studied. Doubling concentrations of methacholine were given to a maximum of 32 mg/ml or until a 20% fall in forced expiratory volume in one second (FEV1) occurred (provocation concentration, PC20FEV1). Bronchial hyperresponsiveness was defined arbitrarily as a PC20FEV1 of 2 mg/ml or less (or 11 mumol cumulative dose, PD20FEV1). The prevalence of bronchial hyperresponsiveness was 23%. Bronchial hyperresponsiveness was not associated with age but was more prevalent in women than men (31%:13%). It was also more common in those who had ever wheezed (39%) and in those who had had an attack of rhinitis in the preceding month (45%, p less than 0.1), in atopic individuals (30%), and in smokers (32%), but it was not associated with cough or dyspnoea. There was a positive correlation between PC20FEV1 and resting FEV1 (r = 0.288) and a negative correlation between PC20FEV1 and mean daily peak flow variability (r = -0.356). Stepwise binary logistic regression analysis showed significant independent effects on PC20FEV1 for mean daily peak flow variability, gender, number of positive skin test responses, resting FEV1, and mean histamine skin weal area, but no relation with smoking or mean allergen weal area. The prevalence of bronchial hyperresponsiveness was much higher than the prevalence of diagnosed asthma in the practice in 1984 (4.9%). Analysis of case notes of 169 individuals showed that those with bronchial hyperresponsiveness had not attended the practice more frequently for respiratory complaints during the previous five years. PMID- 2256017 TI - A simple method for correcting single breath total lung capacity for underestimation. AB - The single breath method underestimates total lung capacity by comparison with the multiple breath method (TLCmb) because of inhomogeneity of ventilation distribution. This study proposes a simple correction for the single breath TLC (TLCsb), using inert gas phase III slope to account for the effects of uneven ventilation distribution. A model of a non-uniform lung ventilation was designed, composed of a serial dead space and two alveolar compartments arranged in parallel, whose relative ventilations were determined from the phase III plateau. Before correction TLCsb was 104-44% of TLCmb in 64 subjects (17 with diffuse interstitial disease, 42 with chronic obstructive pulmonary disease, and five healthy subjects). The limit of acceptability for the correction (TLCcorr) was determined from the 95% confidence interval of TLCsb/TLCmb in the healthy subjects. The correction resulted in a significant increase in TLCsb (p less than 0.004). TLCcorr remained under the limit of acceptability for only 12 patients with emphysema, and all 12 showed a large improvement in the TLC estimate. The presence of poorly ventilated zones during a single breath in these patients may explain this partial correction. PMID- 2256018 TI - Collagen of the dystrophic hamster diaphragm. AB - The collagen content of the diaphragm was measured in normal and dystrophic hamsters aged 130 and 270 days. The diaphragm collagen content was greater in dystrophic hamsters than in control hamsters of the same age. The effect was greater in the older hamsters whether the collagen content was expressed in terms of the percentage of dry weight, in relation to surface area, or as total collagen. This increase was apparently at the expense of muscle tissue and may be a major factor contributing to respiratory muscle weakness as dystrophy advances. PMID- 2256019 TI - Cystic fibrosis. Introduction. PMID- 2256020 TI - Cystic fibrosis. 1. Pseudomonas aeruginosa infection in cystic fibrosis and its management. PMID- 2256021 TI - Assisted ventilation. 2. Indications for mechanical ventilation. PMID- 2256022 TI - Pulmonary complications of intravenous drug misuse. 1. Epidemiology and non infective complications. PMID- 2256023 TI - Lung fibrosis induced by Thorotrast. AB - A 63 year old woman developed progressive shortness of breath, pulmonary hypertension, and respiratory failure and died from pulmonary fibrosis 45 years after thoracic fistulography with Thorotrast. Bouts of acute respiratory failure occurred with features of noncardiogenic pulmonary oedema. Lung tissue obtained by biopsy and at necropsy showed abundant radioactive particles of thorium dioxide in the lungs. The particles were congregated in the walls of blood vessels and in perivascular fibrous zones, consistent with a causal role of Thorotrast in the development of lung fibrosis. It is suggested that the fibrosis was due to the combined effects of alpha radiation on the interstitial perivascular zones and of recurrent pulmonary oedema due to endothelial damage. PMID- 2256024 TI - Adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung. AB - Two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma. No other known precipitants were evident. The adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors. Tumour related blood borne factors may have contributed to lung injury in these cases. PMID- 2256026 TI - Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule. AB - A symptomless 58 year old man had an eosinophilic granuloma of the lung that presented as a solitary pulmonary nodule rather than the usual diffuse reticulonodular shadow on the chest radiograph. Only one previous case presenting in this way has been described. PMID- 2256025 TI - Diffuse alveolar haemorrhage associated with progressive systemic sclerosis. AB - A 41 year old man with an eight year history of progressive systemic sclerosis developed severe diffuse alveolar haemorrhage and died. The importance of diffuse alveolar haemorrhage as a rare but potentially serious complication of connective tissue disease should not be overlooked. PMID- 2256027 TI - Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease. PMID- 2256028 TI - [The function of the university--its role in health care?]. PMID- 2256029 TI - [Women physicians--towards academic equality?]. PMID- 2256030 TI - [Children and drugs]. PMID- 2256031 TI - [Prescription of drugs in Norway to children aged 0-12 years]. AB - The first part of a project initiated at the Department of Pharmacotherapeutics, University of Oslo, on use of drugs in the treatment of children involved a study of prescriptions in September 1986. All pharmacies in the country were asked to record all drugs prescribed to 0-12 year old children during one week. 87% of all Norwegian pharmacies took part in the study and data were recorded for 7,587 prescribed drugs. Drug prescribing was highest in the county of Hedmark, and lowest in the county of Troms. For the age group 0-10 years 23% more drugs were prescribed to boys than to girls. Infants (0-1 year) were prescribed drugs ten times more often than the oldest children. 3% of the infants (0-1 year) were prescribed drugs during the week the study took place. More than 43% of the total prescriptions were for drugs for the respiratory organs. Antasthmatics comprised the largest subgroup (796 prescribed drugs). Boys were prescribed 65% more antasthmatics than girls. Every 20th of the total prescriptions was for an oral decongestant. There are few rational reasons for prescribing drugs in this group. As a single group, systemic antibiotics were the drugs most often prescribed, and accounted for as much as 30% of the total prescriptions. The observed choice of antibiotics does not seem to agree with Norwegian recommendations. PMID- 2256032 TI - [Rising admission of children with asthma]. AB - Admissions and readmissions of children with asthma to the Paediatric Department, Sentralsykehuset i Akershus, increased from 197 in 1986 to 318 in 1988. The hospitalization period for children under two years of age with more than one admission has increased, which may indicate more severe asthma within this age group. Admissions for pneumonia have increased from 35 to 90, while admissions for bronchiolitis and laryngitis have remained stable. The distribution of number of admissions per 1,000 of the population is irregular. The frequency of admissions is no higher for the large communities around Oslo, exposed to motorways, traffic and heavy industry, than for the more rural communities. This may suggest that air pollution is not the major cause of the observed increase in the numbers of admissions to our department. PMID- 2256034 TI - [Prediction of the extent of heterosexual HIV infections in Norway in the 1990s]. AB - Using a mathematical model, the extent of heterosexual HIV-infection in the years 1987-2000 is assessed on the basis of population-based data on sexual behaviour and data from the surveillance system for HIV-infections. The most probable prognosis give about 200 new cases of heterosexual HIV-infection per year at the end of the period, with a prevalence of HIV-infection of about 1,000 persons in the year 2000. According to the prognosis about 50 new cases of heterosexually acquired AIDS will occur per year in the late 1990s. The discrepancy between a high prognosis and a low prognosis is several hundred cases of HIV-infection per year. More precise prognoses will depend on routine collection of population based data on risk behaviour and spread of infection. PMID- 2256033 TI - [Pregnancy and iron storage]. AB - We present the results from a study of 97 female blood donors who reappeared for donation after giving birth from nine to 60 months before. The donors answered a questionnaire about number of pregnancies, the time since last pregnancy, iron medication before and during pregnancy, and methods of contraception. Serum ferritin was determined in a blood sample drawn before donation. In this group, mean serum ferritin was 21.5 +/- 14 micrograms/l. In a control group consisting of young women who registered as donors the mean serum ferritin was 39.4 +/- 29.4 micrograms/l. There was a decrease in serum ferritin with increasing age and parity. The mean serum ferritin value was higher among women who had taken iron supplements regularly before and during pregnancy than among women who had not taken iron supplements. The differences were statistically significant for iron supplementation during pregnancy. Iron supplements during pregnancy seem justified, but further information should be obtained about necessary does and appropriate time for starting supplementation. PMID- 2256035 TI - [Surgeons opinion about cytostatic treatment of gastrointestinal cancer]. AB - Surgeons' opinion on several aspects of the treatment of gastrointestinal cancer with cystostatic drugs was investigated by means of a questionnaire to 51 departments. 48 replied. The surgeons were generally critical of the use of chemotherapy for cancer in the oesophagus, pancreas and stomach. More than half of the surgeons considers that fluorouracil can be used to treat recurrent or metastatic disease of the colon/rectum. A few would use fluorouracil against the other kinds of cancer too. Psychological aspects are considered to be important both for the decision to use chemotherapy and for post-operative control. PMID- 2256036 TI - [Bacterial resistance against beta-lactam antibiotics]. AB - Beta-lactam antibiotics include the penicillins, cephalosporins, oxacephems (moxalactam), carbapenems (imipenem) and monobactams (azthreonam)--all with a common beta-lactam ring. Beta-lactam antibiotics block the synthesis and growth of the bacterial cell wall by binding to penicillin-binding proteins on the cytoplasma membrane. The bacteria may escape the effect of beta-lactam antibiotics by reducing the permeability of the cell wall (gramnegative bacteria), by producing beta-lactamases, by reducing the affinity for beta lactams in their penicillin-binding proteins, or by developing tolerance to beta lactam antibiotics. A combination of these resistance mechanisms may be found in the most resistant bacteria, such as Pseudomonas, Serratia and Enterobacter; bacteria often involved in nosocomial infections. Increased antibiotic pressure may select for beta-lactam resistance among other bacteria as well, such as staphylococci, streptococci, Haemophilus influenzae, meningococci and gonococci. Prudent use of antibiotics is mandatory essential to ensure a bactericidal effect of this most important and valuable group of antibiotics in the future. PMID- 2256037 TI - [Cerebral metastasis in Hodgkin's disease]. AB - The article describes the case history of a 31 year old woman with a solitary intracranial metastasis from Hodgkin's lymphoma, and reviews the relevant literature. Metastasis to the central nervous system from Hodgkin's disease is uncommon. This affection is usually a result of metastasis to the meninges or bone, or of direct extension from paracranial or paraspinal lymph node involvement. Hematogenous metastasis of Hodgkin's disease confined to the brain is rare. Affection of the central nervous system is most common in lymphocyte depletion Hodgkin's disease. A higher frequency is seen in advanced clinical stages. The prognosis is poor. PMID- 2256038 TI - [Dementia in the elderly. A 3-year project]. AB - In order to meet the need of proper examination and treatment of memory problems in the elderly a specialized unit of psychogeriatrics has been established as a pilot project. In the period from September 1986 to April 1988, 146 persons were examined, 42% as outpatients and 58% as inpatients. The average age was 75.3 years. 54% had dementia senilis and 16% other sorts of dementia. 30% were not demented: 14% had a psychiatric illness, 8% organic damage or illness of the brain and 7% were confused. Overdose or wrong use of psychopharmacological drugs was a frequent problem, and cutting out the medication, regulating the dose, or changing to another medicine had surprising consequences. The further treatment was planned in cooperation with the patient's family and the community health service. A follow-up after nine months indicated that this was a positive procedure for the patients, and that the unit was a professional resource to the local health services in the whole district. The hospital has now been allocated funds from the Government to function as a competence centre for part of Eastern Norway. PMID- 2256039 TI - [Diagnosis using synovial fluid]. PMID- 2256040 TI - [The patients' and referring physicians' evaluation of the benefit of examination by a specialist]. AB - 60 patients and their referring general practitioners were asked to evaluate the benefit of examination by a rheumatologist in an out-patient clinic. A large percentage of the patients (73%) and of the GPs (89%) were satisfied with the outcome of the examination, even though only 29% of the patients and 37% of the GPs thought that the advice given by the specialist had helped. A majority (60%) of the patients would have liked to have received more information from the specialist, about the diagnosis, and 49% patients claimed that they had not been given any advice on treatment. The results of this study will lead to a change in how we inform patients about diagnosis and treatment in our out-patient clinic. PMID- 2256041 TI - [Mesalazine in Crohn disease]. PMID- 2256042 TI - [Calcium antagonists]. PMID- 2256043 TI - [Women physicians. Developmental tendencies in specialization and career patterns]. AB - An earlier study showed that female doctors were found in specific subgroups of the medical profession. Their choices were probably governed by traditional ideas about feminine versus male role-expectations. This study shows that there still exists marked sex differences within the medical profession. Female doctors are still to be found in specific specialities. Seen in relation to male doctors the degree of specialization among female doctors decreased from 1972 to 1986. This is probably due to the fact that there are many young female doctors who have not yet completed their specialization. In married couples of doctors on the contrary, there is an increasing tendency towards equality of professional career, since the female partner now more often reaches the same career level as her husband, and with less lag in time. PMID- 2256044 TI - [Community health services--more stressing for female than male physicians?]. AB - A questionnaire was sent to all general practitioners at municipal health centres in Oslo in 1987. 74% of the doctors participated in the study, 38 women and 41 men. The results show that the major source of stress at work was high work load. The results also point to important gender differences. Compared with their male colleagues, the female general practitioners experienced higher job strain. They also found less opportunity to influence their working conditions. Female doctors more often experienced psychosomatic disorders and periods of sick leave. The results are discussed in relation to differences in patient selection, role strain and coping style. PMID- 2256045 TI - [Gender neutrality in medical research--possible and desirable?]. AB - Medical science has been produced by men. A female surgeon concludes that, compared with complications in male patients, complications in female patients have been underrepresented in medical literature. In surgery the choice of fields of research and surgical methods is based mainly on the personal evaluations of the scientists, (female or male), and only partly on legitimatized scientific parameters. There are still very few women researchers in medical science. This science should be produced by both male and female researchers if it is to be equally fair and offer equally good medical service to female and male patients. PMID- 2256046 TI - [Acute respiratory distress syndrome in adults]. PMID- 2256048 TI - [Internal medicine--fragmented or whole?]. PMID- 2256047 TI - [Diagnostic prick tests]. PMID- 2256049 TI - [Treatment for all or health for all?]. PMID- 2256050 TI - [Transfer of patients between hospitals]. PMID- 2256051 TI - [Pleuroperitoneal shunt in recurrent pleural effusion]. AB - Recurrent pleural effusion is often a problem in metastases from breast cancer, and may be treated by instillation of irritating drugs combined with external drainage for some days. Less frequently chylothorax is a complication to malignant disease. Drainage of the pleural effusion to the peritoneum is possible, and this article describes how four patients with metastases from breast carcinoma and one patient with chylothorax caused by malignant lymphoma were all treated successfully from 40 days to ten months by means of a simple siliconated T-shaped drain from the pleural cavity to the peritoneum. In one patient the drain occluded after three months. It does not seem to be necessary to use drains with valves for this purpose. PMID- 2256052 TI - [Dorsal dislocation of the metacarpophalangeal joint of the index finger]. AB - Dorsal dislocation of the index metacarpophalangeal joint, although uncommon, is a serious injury. An open reduction is usually necessary. In the present case, an open reduction was performed by a dorsal approach. The pathological anatomy is described. PMID- 2256053 TI - [Mollaret's meningitis]. AB - Mollarets meningitis is a rare form of recurrent aseptic meningitis where a diagnostic feature is the characteristic cytologic picture in the cerebrospinal fluid. The article presents two cases that were clinically diagnosed as Mollarets meningitis. The cytologic picture of the cerebrospinal fluid is described and the major clinical aspects and the differential diagnoses are discussed briefly. PMID- 2256054 TI - [Ultrasonography of strangulated Richter's hernia]. AB - Ultrasonography may show early pathological changes in an obstructed intestine and also identify abnormal structures in the abdominal wall and inguinal region. We describe a patient with intestinal obstruction due to a femoral hernia of Richter's type. The hernia was shown well by ultrasonography. Ultrasonic examination of the abdomen, including the inguinal regions, may facilitate earlier diagnosis in patients with acute abdominal disease. PMID- 2256055 TI - [A comparative study of absorption of 2 organic selenium preparations and a placebo]. AB - In a double blind study three groups of healthy men 20-49 years of age were given 200 micrograms of l-selenium-methionine, peaselenium or placebo daily. L-selen methionine was absorbed much better than peaselenium. The different was significant. There was no difference between absorption of peaselenium and of the placebo. PMID- 2256056 TI - [The role of internal medicine in health services--time for retirement?]. AB - Internal medicine is more than a hundred years old, even in Norway. Its intellectual fundament originates from nineteenth century medicine in Germany. Traditionally, these German physicians covered the entire field of medicine. However, due to lack of therapeutic remedies their main emphasis was on diagnosis and prognosis. During the last sixty years the tremendous increase in medical knowledge has led to a strong tendency towards organ specialization. The generalists in hospitals have met competition from general practitioners and specialists in geriatrics. At the same time their domain has steadily shrunk as the number of medical hospital beds has been reduced. Although not to the advantage of the patients, progress is wiping out the hospital generalists. Most (90%) hospital doctors are now organ specialists, although the majority of patients admitted to medical departments have diseases in more than one organ system. Therefore, generalists should be at least as equally appreciated as the organ specialists. To save the generalists the educational system must be changed. The two types of specialists should follow their own educational paths qualifying to separate and independent competence areas (general or organ specific). Medical departments should be encouraged to maintain general sections in addition to the organ-specific sections. The generalist and the organ specialist should be professionally united in their efforts to develop internal medicine as a discipline. PMID- 2256057 TI - [Internal medicine--limited or wide medical specialty?]. AB - 980 consecutive admissions to the medical department of Aker Hospital were analyzed in order to determine the extent to which the department deals with problems not related directly to the field of internal medicine. 709 patients (72%) were admitted for purely medical conditions. These patients occupied 49% of the beds. In 121 cases (12%) the main reason for admission involved other specialities. 209 admissions (21%) involved conditions other than somatic disease. Patients waiting for transferral to permanent nursing homes occupied 16% of the beds. Most patients needed hospital care, and many suffered from complex medical conditions. These factors advocate a liberal admission policy. On the other hand, medical departments should be relieved of responsibility for patients whose primary requirement is long-term care. PMID- 2256058 TI - [Reflections on the professional and organizational development of internal medicine]. AB - A steadily increasing body of knowledge has led to the current system of specialization and sub-specialization in medicine. A potential danger is sub subspecialization and fragmentation of service to patients. Internal medicine must therefore remain undisrupted and given possibilities of growth. The foremost challenge of internal medicine today is to further develop its own diagnostic and therapeutic culture. Traditionally, the internist has been the advocate of rational clinical diagnostics. Clinical diagnostics must remain the starting point of the diagnostic process. Our therapeutic culture is linked in particular to conducting and analysing large clinical trials. Internal medicine is also playing an increasingly important role in the organization of proper care for the old and the dying. PMID- 2256059 TI - [Admissions to the medical wards. Are resources used in accordance to patients' needs?]. AB - Medical and social data on 980 consecutive admissions to the Medical Department, Aker Hospital, Oslo, were recorded prospectively with emphasis on patients' requirements and the Department's use of available resources. 73% of the admissions were acute, 4% were considered unnecessary. Half were because of chronic illness. Although 88% of the patients' requirements could have been met at a local hospital, 59% were treated in specialized units. 12% were admitted to the day unit at reduced cost for an average stay of three days. 41% of the patients were over 70 years of age, 37% lived alone and 14% needed rehabilitation. A main reason for admission was the patient's inability to take care of him/herself at home, in nearly all cases the main reason being acute illness or deterioration. Therefore many of the patients seemed to need care in an acute geriatric unit. At any one time the reason for 20-25% of the patients being in the department was delay in providing care at home or in a nursing home. PMID- 2256061 TI - [Liver transplantation in fulminant hepatic failure]. AB - The prognosis for patients suffering from fulminant hepatic failure is still poor. The possibility of performing liver transplantation has improved the outcome for the patient. The article presents three cases illustrating some of the difficulties in selecting patients for transplantation, and discusses clinical and laboratory monitoring of patients with fulminant hepatic failure and criteria for selecting patients for liver transplantation. PMID- 2256060 TI - [Transcription regulation--how are genes turned on and off?]. AB - During the last 20 years much has been learned about regulation of gene activity, or transcription. Regulations are more complex in higher organisms, such as humans, than, for instance, in viruses and yeast. Therefore most of our present knowledge about gene regulation is derived from such simple systems. Recent results now suggest that a few simple mechanisms for gene activation may be shared by unrelated organisms like bacteria, yeast, flies and humans. PMID- 2256062 TI - [Intraosseous infusion. A rapid and safe vascular access in emergencies]. PMID- 2256063 TI - [Preservatives and dental caries. Can preservatives in food and beverages influence oral health?]. AB - There has been a pronounced decline in dental caries in industrialized countries during the last decades. The most obvious explanation is exposure to fluorides. However, the decline started before fluorides were extensively used. Theoretically, a contributory factor may have been increased consumption of foods containing preservatives. The aims of the present study were to find out whether increased intake of preservatives has occurred, and to assess the effect of two commonly used preservatives, sorbic acid and benzoic acid, on bacterial growth and on plaque acidogenity in vivo. Results from five consumption reports from the Central Bureau of Statistics of Norway were used to estimate changes in consumption of basic foods containing the preservatives mentioned. A modified broth dilution method was used to determine the growth inhibitory effects on selected oral streptococci. Plaque-pH measurements were performed with a microelectrode to assess possible effects on acid production. Data pointed towards increased consumption of preservatives. Legal concentrations of preservatives inhibited bacterial growth. Similar concentrations of the preservatives had a negligible effect on acid production in dental plaque (0.4% W/V), whereas higher concentrations (2% W/V) had an inhibitory effect. PMID- 2256064 TI - [Health education in the communities. A survey conducted in 1987]. AB - Health education in the primary health sector in Norway is to be strengthened. The recently implemented health service reform (1984) is intended to stimulate the development of health promotion and health education in the municipalities. A survey on municipality involvement in health education was conducted in 1987, and showed a higher level of activity as well as an increased interest in the subject among health professionals. However, when the official policy is compared with the local situation several discrepancies are revealed: no substantial improvement of health education methodology has appeared; cooperation with non governmental organizations is less than anticipated; and health education is normally not directed at local politics or participation. The chosen strategy for governmental control, characterised by decentralising the decision-making process, has not been found to be sufficient to ensure a stronger emphasis on primary prevention and health promotion. In 1989 a nation-wide five-year programme to stimulate local health promotion was launched by the Ministry of Health and Social Affairs in cooperation with the Directorate of Health. A research programme on health promotion has also been started, administered by the Medical Research Council. PMID- 2256065 TI - [A campaign against home accidents--accident prevention efforts in the communities]. AB - A nation-wide campaign aimed at preventing accidents in the home is being implemented in Norway. 95% of the municipalities acknowledge having received information material from the campaign, 33% report having established accident prevention committees, and 26% report having introduced preventive measures as a result of this national campaign. The study indicates that accidents are not recognized as yet as a major health problem in many municipalities. Identification of accidents as a health problem seems to be an important factor in the preventive efforts. To enhance further accident prevention efforts it seems important to increase awareness of accident as a health problem, and to increase the involvement of key personnel within the community. PMID- 2256066 TI - [Consequences of changing from fixed amount payments to percentage payment of drugs]. AB - Two pharmacies in Drammen recorded and analyzed 1,155 prescriptions in February 1989. The purpose was to compare the proportion of costs paid by customers and national reimbursement by percentage patient copayment (20%) and fixed amount as copayment (NOK 60). On average the patient's copayment increased by 23.9%. All prescriptions below NOK 300 were cheaper for the patient by percentage copayment, while all above NOK 300 were more expensive. For medical equipment items the copayment increased by 74%. When calculated for Norway the increase in patient copayment amounts to about NOK 50 million. The costs of reimbursement were reduced by 2.4%. About 30% of the total reimbursement refers to cardiovascular diseases. PMID- 2256067 TI - [The reliability of qualitative medical research]. PMID- 2256068 TI - [Child day care centers and infections--child day care centers are healthy]. PMID- 2256069 TI - [Transmission risk of hepatitis B and human immunodeficiency virus among employees at Norwegian hospitals]. PMID- 2256070 TI - [Diagnosis of suicidal tendencies]. PMID- 2256071 TI - [Is the customer always right?]. PMID- 2256072 TI - [Kala-azar]. PMID- 2256073 TI - [Diabetes care in Norway--a letter to a good friend who has diabetes]. PMID- 2256074 TI - [What do patients think of primary health care? A questionnaire study among patients in Northern Norway in 1987]. AB - Doctors and professional health administrators have been the principal decision makers and the patients have hardly had any direct influence on the planning and organization of primary health care in Norway. In 1987, in order to draw attention to patient opinions, the Institute of Community Medicine, University of Tromso, conducted a questionnaire survey among patients attending general practices in North Norway. The question were selected to cover issues in the contemporary debate on the ideology, organization and standards of services of general practitioners. 36 teaching practices in the region were included in the survey. Altogether 3,739 questionnaires were returned, a response rate of over 60%. The respondents reported more than 16,000 consultations during the last year. This paper presents the methods used and the main findings concerning the representativeness of the results and the potential for generalization. Subsequent publications will present detailed results from the study within the framework of patient experiences, preferences and expectations. PMID- 2256075 TI - [A personal physician, wishes and realities in Northern Norway. A patient study in Northern Norway in 1987]. AB - Among patients consulting general practitioners in northern Norway, 57% had a stable relationship with one doctor, according to answers to a questionnaire. Rather than having a free choice between several doctors, 85% preferred to have a personal doctor. About half the patients wanted the same doctor for the whole family. Even if they had to wait longer for the consultation, 63% would prefer to meet their own doctor. A personal doctor was much less common in northern Norway than in the rest of the country, which could be put down to lower stability in the practices. PMID- 2256076 TI - [Accessibility and waiting time in general practice. A patient study in Northern Norway in 1987]. AB - In the opinion of the public, accessibility is probably one of the most important features of general practice. More than 3,500 patients in North Norway answered a questionnaire asking for their opinions on waiting time for consultation, the time spent in consultation and the possibility of the doctor visiting them at home. 80% thought that a waiting time of more than one week was too long. The actual waiting times differ considerably, but only a few practices serving less than 900 inhabitants per physician managed to satisfy their patients. On the other hand, about 80% found the time allocated for the consultation to be adequate. Almost half the patients who expressed an opinion thought it too difficult to get a doctor to visit them at home. Less than 10% considered a long distance to travel to a doctor to be an obstacle. Not surprisingly, young people were most demanding as regards quick service. Men were somewhat more satisfied than women, as were patients in rural areas compared with patients in the towns. In our opinion, some of the patients' causes of dissatisfaction can be removed by better routines. However, it seems that the resources available within general practice, are inadequate to meet all the patients' wishes, either now or in the future. PMID- 2256077 TI - [At what time during a the day do patients want to see the physicians? A patient study in Northern Norway in 1987]. AB - 3,739 patients in North-Norway were asked about the preferred time of day for an appointment with the doctor. One in five indicated a time outside current opening hours. The oldest patients, and those living in rural areas, were the groups who preferred current opening hours. More than half the patients aged 21-64 indicated that the time they preferred was during their own free time. The study shows that an adjustment in the opening hours of doctors' practices is necessary if the patients' wishes are to be accommodated. PMID- 2256078 TI - [Visceral leishmaniasis (kala-azar)]. AB - Visceral leishmaniasis is a serious zoonosis which has very rarely been diagnosed in Norway. We report a case of visceral leishmaniasis in a Norwegian patient, and present an up-to-date review of the disease. We conclude that this disease should be considered even in Scandinavian patients if the appropriate symptoms and signs are present and there has been possibility of exposure. Simple blood tests and serum electrophoresis are of considerable value. If possible, the protozoa should be demonstrated by microscopy of bone marrow aspirate. We also discuss the identification of the parasites in bone marrow biopsy, which should be performed in pancytopenic patients. The diagnosis should be confirmed by culture or a serological test. PMID- 2256079 TI - [What happens during the first encounter between a patient and a physiotherapist?]. AB - Doctors refer several patients with problems connected to muscles and joints to physiotherapists. What happens when the patient meet the physiotherapist? This question is the starting point for a research project on first encounters in physiotherapy practice focusing on function assessment and communication. The analysis is based on videotapes of the encounters and semistructured interviews with patients and physiotherapists. This article is based on one of the videotaped encounters. The analysis assumes that all actions convey messages. Professional actions are interpreted in a communicative perspective. It appears that the patient's presentation of her problems is to some extent excluded from the therapeutic frame of understanding. The encounter displays problems and challenges between the person seeking help and the professional PMID- 2256080 TI - [Cooperation between a physiotherapist and a physician in connection with psychomotor physiotherapy]. AB - Experience has shown that active cooperation between the physiotherapist and the doctor is of major importance when using psychomotor physiotherapy. This is partly because not all patients are suited to this special form of treatment, and partly because of the need to involve the doctor actively in the treatment situation, should the physiotherapist not observe any progress. The most usual reason for lack of progress is emotional factors which cause muscular tension and these must be uncovered and treated before the physiotherapy can continue. PMID- 2256081 TI - [Contraception guidance in general practice. A questionnaire study in Nordland, Troms and Finnmark]. AB - 239 (75%) of 318 general practitioners in the three northernmost counties of Norway were asked by mailed questionnaire to report the frequency of consultations on contraception, and what kind of contraception they usually recommended. 85% informed the women about at least three different alternatives; oral contraceptives, intrauterine devices and condoms. Almost 50% would ordinate an intrauterine device to a woman who never had been pregnant. 60% informed the woman about other alternatives even if she had already decided upon method prior to the consultation. The physician often brought up the subject of contraception, but as many as 15% did not, as a routine, mention birth control when a woman consulted them for a first trimester abortion. Almost 50% did not know how to fit the diaphragms. PMID- 2256082 TI - [Do male and female physicians give the same contraception guidance?]. AB - A questionnaire on their practice regarding ordination of contraceptive methods was answered by 239 (75%) of the general practitioners in the three northern most counties of Norway. The female doctors reported a higher frequency both of female patients and of consultations for birth control, and were more active in these consultations than their male colleagues. Female doctors suggested more methods to their patients, and had a more positive attitude to barrier methods. 61% of the male doctors and 27% of the female doctors had no experience of fitting diaphragms. PMID- 2256083 TI - [Guidelines for insertion of intrauterine devices]. PMID- 2256084 TI - [Conscious and unconscious awareness during anesthesia--how deep is the patient's sleep?]. AB - A review is given over the aspects of awareness during general anaesthesia. Traditional clinical signs for evaluating depth of anaesthesia can be supplemented by objective methods such as EEG, cerebral function monitor and sensory evoked potentials. However, it has been difficult to establish the practical applications of these methods. Awareness can be graded from the obvious form, with recall of intraoperative events, to an unconscious form where the memory can be activated through special psychological techniques. We discuss the possibility of using unconscious perception of auditory signals for positive instructions to patients under anaesthesia. PMID- 2256085 TI - [How important is it for the patient to have a personal physician? A study of patients' attitudes and views on the accessibility of alternative health services in Bergen]. AB - In this survey, 600 respondents over the age of 25 chosen at random from two districts in the city of Bergen were asked about their own and their families' pattern of use of health services, particularly their use of physicians. 87% of the adults and 80% of the children reported having a "family doctor". The ties to these physicians were weak, however, since only 34% of the respondents said they would contact their family doctor if taken ill during normal consulting hours. Consequently, the term "family physician" seems to be used somewhat inaccurately in Norwegian health care. PMID- 2256086 TI - [The accessibility of general practitioners by the phone. A study in Vestfold based on calls]. AB - The accessibility by phone of 35 general practitioners during consulting hours was tested systematically. The doctor was accessible in the case of 74% of all calls, no answer was obtained in 15%, and in 11% the office was inaccessible due to the use of an automatic telephone answerer. In the authors' opinion the standard should be 90% accessibility by phone for general practitioners in primary health care. This standard was met by 20% of the doctors. PMID- 2256087 TI - [The importance of cooperation in primary health care. Utilization of physicians' services and home nursing services during different degrees of cooperation]. AB - A study carried out in the county of Vestfold in the spring of 1989 clearly showed how cooperation between doctor and nurse influenced the level and quality of care provided by doctors to patients nursed at home. Good cooperation coincided with high quality health services, and ensured rational use of resources in relation to the patients' needs. The study showed that the quality and frequency of cooperation between doctor and nurse are of utmost importance for the service given to the patients. PMID- 2256088 TI - [The accessibility of patients' personal physicians and quality of care of patients under home nursing care]. AB - A study was carried out in the county of Vestfold in the spring of 1989 to establish the quality and quantity of the medical services for patients nursed at home. The study showed that doctors in rural districts provide better service than doctors in the towns. This difference is particularly noticeable in the case of patients who are acutely ill. The study also showed that patient-doctor contacts are seldom for patients nursed at home, with an average frequency of one every eight weeks for consulting-room consultations and one every 15 weeks for visits to the home. PMID- 2256089 TI - [Information technology in health care--a fiasco so far?]. PMID- 2256090 TI - [Depressive reaction after labor--more than stress and hormones. Reflections on some normal psychological and psychodynamic causative connections]. PMID- 2256091 TI - [A combination effect of mianserin (Tolvon) and tricyclic antidepressive agents. Improved antidepressive therapy]. PMID- 2256092 TI - [Streptococcal infections]. PMID- 2256093 TI - [Therapeutic considerations on withdrawal of life support of infants]. PMID- 2256095 TI - [Extra zinc oxide in swine fodder... Why not!]. PMID- 2256094 TI - [Epidemiology and immunology of trichostrongylosis in cattle and sheep, a synthesis]. AB - The connections between the epidemiology of trichostrongylosis in cattle and sheep and immunological phenomena are discussed. It is concluded that the build up and the reduction of immunity greatly determine the epidemiology of trichostrongylosis. Regulation of immunity and the development of vaccines produce more questions than good prospects for the time being. PMID- 2256097 TI - [Mucosal immunity]. AB - The mucosal immune system protects against infections that enter the body via the mucosae. This article describes how the mucosal immune system functions and how mucosal immune responses can be induced by vaccination. It also discusses various vaccination regimens that maximize the induction of mucosal immune responses against bacterial and viral infections. One paragraph of the article discusses the possibilities of developing vaccines that induce a mucosal immune response against parasite infections. PMID- 2256096 TI - [Changes in the histochemical composition of mucins in goblet cells in the course of a Nippostrongylus brasiliensis infection in the rat]. AB - Rats were infected with Nippostrongylus brasiliensis, and changes in the histochemical composition of mucins in jejunal goblet cells were investigated. Ten days after infection, mitotic activity was extensively in jejunal crypts: both crypts and villi were characterised by hyperplasia of goblet cells. Infected rats had a markedly greater number of crypt and villi goblet cells containing neutral mucin than the control rats did. Moreover, 15 days after infection, infected rats had significantly more goblet cells containing acid mucin than control rats did. In infected rats, the acid mucins in goblet cells (day 15) appeared to be predominantly sulphomucins, whereas in control rats the acid mucins were predominantly sialomucins. The experiments established that when N. brasiliensis is excreted by rats, the histochemical composition of mucins in crypt and villi goblet cells has been changed not only quantitatively, but also qualitatively. PMID- 2256098 TI - [Ivermectin poisoning]. PMID- 2256099 TI - [No heartworm disease in the Netherlands?]. PMID- 2256100 TI - Anti-idiotypic antibodies directed against anti-HBs among the patients with chronic hepatitis B. AB - Anti-idiotypic antibodies (anti-Id) against anti-HBs were found in the sera of patients with chronic hepatitis type B. Anti-idiotypic antibodies were detected by an enzyme-linked immunosorbent assay using horseradish peroxidase conjugated mouse monoclonal anti-HBs. Ten of 72 HBsAg positive sera contained anti-Id (13.9%). The prevalence of anti-Id did not appear to correlate with HBeAg/anti HBe system. However, HB virus specific DNA polymerase activity was significantly higher in anti-Id positive sera. In the sera obtained from the patients treated with predonisolone before, anti-Id positive rate was higher than that in the patients without a history of predonisolone therapy. These results suggest that anti-Id may be related to the immunoregulatory mechanism of HB virus replication. PMID- 2256102 TI - Changes in the intercellular junction of rat exocrine pancreatic cells induced by long term ethanol ingestion. AB - The findings of electron microscopic observation of the intercellular junctions of pancreatic exocrine cells from male Wistar rats that had been given ethanol ad libitum in place of water are described. In control animals, numerous tight junctions having a distinct pentalamellar structure were observed in the well developed interdigitations of the baso-lateral domain of both the ductal and centroacinar cells. This type of junction differed structurally as well as topographically from the occluding junctions situated in the apical part of the lateral domain and exhibited a tri-lamellar rather than a penta-lamellar structure. Further, this type of junction was not observed in the interdigitations between the acinar and centroacinar cells or in those between acinar cells. These specialized membrane structures became hypertrophic after 1 and 2 months of ethanol ingestion. That is, the interdigitated cell processes became elongated but the distribution density of the tight junctions was similar to that in control animals, so that the total number of tight junctions increased. After 3 months of ethanol ingestion, the interdigitated cell processes atrophied, the intercellular spaces widened, and the number of tight junctions markedly decreased. Thereafter, these changes were observed continuously in ethanol-treated animals. However, the occluding and adhering junctions were not markedly affected by ethanol intake. PMID- 2256101 TI - Liposome-encapsulated amphotericin B in the treatment of experimental murine candidiasis. AB - The efficacy of liposome-encapsulated amphotericin B in treating experimental murine candidiasis was compared with that of the commercially available amphotericin B (Fungizone). The LD50 of liposomal amphotericin B in ddY mice exceeded 10.0 mg/kg while that of Fungizone was 3.0 mg/kg. Experimental candidiasis was induced by injecting a clinical isolate of Candida albicans strain 0925-107-01, through the tail vein. With the injection of 1.7 x 10(6) colony forming units, the number of colonies in the kidneys remained between 2.1 x 10(5) and 1.2 x 10(6), whereas the number of colonies in blood, liver, spleen, lungs and heart decreased rapidly. Histological examination revealed severe pyelonephritis with fungal infiltration and a mild invasion of the heart, lungs, liver and spleen. The survival rate of mice with experimental candidiasis treated with Fungizone at a dose of 0.8 mg/kg was 50% (the maximum tolerated dose without acute lethality), whereas all mice treated with the liposomal amphotericin B at a dose of 5.0 mg/kg were alive even 42 days after the inoculation (p less than 0.01). Using liposome as a carrier for amphotericin B decreased this drug's systemic toxicity making it possible to administer doses higher than feasible with the commercial preparation and thus obtaining better therapeutic efficacy. PMID- 2256104 TI - Uncontrolled hypertension is associated with a rapid progression of nephropathy in type 2 diabetic patients with proteinuria and preserved renal function. AB - The relationship between blood pressure and progression of nephropathy was studied (the mean follow-up period of 32.6 +/- 17.9 (S.D.) months in 20 Type 2 (non-insulin-dependent) diabetic patients with clinical nephropathy (proteinuria greater than 0.5 g/day) and preserved renal function (serum creatinine level less than 150 mumol/liter). Fifteen hypertensive patients under antihypertensive treatment were divided into 2 groups: those with the mean diastolic blood pressure greater than or equal to 90 mmHg and/or the mean systolic blood pressure greater than or equal to 150 mmHg during the follow-up period were designated as Group A (n = 6) and the remainders as Group B (n = 9). Five normotensive patients without any anti-hypertensive treatment throughout the follow-up period served as a control group (Group C). The decline rate in GFR was significantly greater (p less than 0.05) in Group A (1.15 +/- 0.39 (S.E.) ml/min/month) than those in Groups B (0.33 +/- 0.08 ml/min/month) and C (0.40 +/- 0.09 ml/min/month), respectively. The decline rate in GFR showed significant positive correlations both with systolic (rS = 0.553, p less than 0.05) and diastolic (rS = 0.493, p less than 0.05) blood pressures in the 15 hypertensive patients. The age, initial glomerular filtration rate, duration of diabetes and mean HbA1c level during the observation period were comparable in Groups A, B and C, respectively. The results indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in Type 2 diabetic patients with overt nephropathy, as has been suggested in Type 1 (insulin-dependent) diabetic patients. PMID- 2256103 TI - Effect of thymic hormones on induction of experimental allergic encephalomyelitis in old mice. AB - This study was aimed at restoring decreased T-cell functions and reduced susceptibility to proteolipid apoprotein (PLP) induced-experimental allergic encephalomyelitis (EAE) in old mice with thymic hormones. Thymosin fraction 5 (TF 5) and serum thymic factor (FTS) had no significant in vitro and in vivo effect on proliferative responses to PLP and concanavalin A (Con A), and on EAE induction in young and old mice. These results suggest that decreased T-cell functions cannot be restored by these thymic hormones tested. PMID- 2256105 TI - Long-term results after repair of tetralogy of Fallot. AB - One hundred sixty-six patients with tetralogy of Fallot including 15 pulmonary atresia repaired since 1971 were analyzed with respect to their physical activities, school or social life, hemodynamics, ECG, reoperation and late mortality. Follow-up period ranged from 1 to 19 years with an average of 9.1. There were 9 late deaths including 4 sudden deaths. Actuarial survival rates at 5 and 13 years were 96.4% and 90.5%, respectively. Eighty-five patients (72.0%) of 118 replied were in NYHA functional class I, 31 (26.3%) in class II and 2 (1.7%) in class III. Thirteen patients (7.8%) demonstrated right ventricular/left ventricular systolic pressure ratio over 0.80 because of inadequate relief of the pulmonary stenosis or obstruction, hypoplasia of the pulmonary artery or external conduit stenosis. Although the left ventricular ejection fraction was maintained at the normal range (0.65 +/- 0.09), that of the right ventricle was below the normal level (0.52 +/- 0.09). Two patients developed complete heart block postoperatively and underwent pacemaker implantations. Complete right bundle branch block was observed in 85 patients including 6 with left axis deviation. Most of the patients after correction of tetralogy of Fallot are in satisfactory conditions. However, some patients have limitations in school or social life because of residual lesions or postoperative complications. It is important to consider the proper operative procedures to avoid these problems. PMID- 2256106 TI - Effects of hand and spatial conditions on visual line bisection. AB - This study examined the effects of hand and spatial conditions on a visual line bisection task with normal right-handers and proposed a normal range of deviation for this task in middle and advanced age. Twenty-four normal dextrals in their fifties and sixties performed a visual line bisection task using either the left or right hand under three spatial conditions: at the midline and in the left and right hemispaces. Our results revealed that performance was significantly affected by the hand used but not spatial conditions: Left hand performance was significantly further leftward than right hand performance. There was no significant interaction between the hand and spatial conditions. The mean deviation of the right hand was 2.2% of the half line length to the right of the true center. The possibility of left unilateral spatial neglect should be considered if a patient bisects a line with a deviation greater than 10% of the half line length to the right. PMID- 2256107 TI - Thin-layer chromatography of urinary neutral oligosaccharides: the detection of blood group-related oligosaccharides and screening for lysosomal storage disease. AB - We devised an improved technique of thin layer chromatography, which permitted the high resolution of urinary neutral oligosaccharides and the qualitative determination of blood group related oligosaccharides as well as oligosaccharides pathologically secreted in lysosomal storage diseases. This procedure can be used inscreening for disorders associated with abnormal excretion of oligosaccharides, as well as in the purification of oligosaccharides. PMID- 2256108 TI - Leucocyte alpha-1,4- and alpha-1,6-glucosidase activities towards oligosaccharides in late onset glycogenosis type II. AB - We describe the partial characterization and some properties of leucocyte alpha glucosidase towards disaccharides with the alpha-1,4 (maltose) and alpha-1,6 glucosidic linkage (isomaltose) and tetrasaccharides with the alpha-1,4 (maltotetraose) and alpha-1,6-glucosidic linkage (tetrasaccharide, Glc alpha 1--- 6Glc alpha 1----4Glc alpha 1----4Glc, which was isolated from the urine of a patient with glycogenosis type II). Leucocyte alpha-glucosidase showed optimal activity towards all four oligosaccharides under two conditions, acidic (pH 4.0 4.5) and neutral (pH 6.0-6.5) regions. Our comparative studies on enzyme kinetics showed that leucocyte alpha-glucosidase was able to hydrolyze both the 1----4 isomers and the 1---6 isomers at acidic and neutral pH. Acid alpha-glucosidase could hydrolyze maltose about 10 times faster than isomaltose, and maltotetraose about 5 times faster than tetrasaccharide isolated from urine. In leucocytes of the patient with late onset glycogenosis type II, acid alpha-glucosidase activities towards maltose, isomaltose, maltotetraose and tetrasaccharide isolated from urine showed 75.3%, 67.4%, 76.5% and 41.4% of normal control values, respectively. Neutral alpha-glucosidase activities towards these four oligosaccharides were normal. Tetrasaccharide with alpha-1,6-glucosidic linkage might be accumulated by the impaired hydrolysis in the circulation as well as the leakage of undegraded glycogen to the circulation from the affected muscle. PMID- 2256109 TI - Mechanisms of hypoxic cell injury. Summary of the symposium presented at the 1990 annual meeting of the Society of Toxicology. PMID- 2256110 TI - Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole. AB - A single, intravenous administration of a low dose of monocrotaline pyrrole (MCTP), a derivative of the pyrrolizidine alkaloid monocrotaline (MCT), induces progressive pulmonary hypertension and right ventricular hypertrophy (RVH) in rats. The temporal relationship between morphologic alterations, biochemical markers of lung injury, and the development of pulmonary hypertension was determined during the developing pulmonary disease. Three days after a single iv injection of 3.5 mg/kg MCTP, small increases in bronchoalveolar lavage (BAL) fluid lactate dehydrogenase (LDH) activity and accumulation in the lungs of intravenously administered 125I-bovine serum albumin (BSA) were associated with minimal to mild interstitial edema around large airways and blood vessels. By Day 5, BAL fluid LDH activity and 125I-BSA accumulation had increased further, and lung weight/body weight ratio and BAL fluid protein concentration were greater than those of control. Interstitial edema was more pronounced and involved patches of alveolar septal walls. A mild increase in numbers of mononuclear cells, including hypertrophied interstitial cells, was evident in these areas. Walls of pulmonary arteries less than 60 microns in diameter were mildly thickened. By Day 8, scattered clusters of alveolar sacs contained serous exudate, and interstitial mononuclear infiltrates were more pronounced. Mild to moderate thickening of arterial walls was apparent in small and large vessels. By Day 14, pulmonary arterial pressure was elevated and RVH was evident. Arterial walls were thickened and had hypertrophy of medial smooth muscle cells and intercellular edema, which was particularly prominent in areas with perivascular interstitial inflammation. Large patches of lung interstitium and alveolar lumens contained serous or fibrinous exudate. In summary, a single, intravenous administration of MCTP induced a delayed and progressive pulmonary microvascular leak, interstitial inflammation, and alterations in muscular blood vessels which resulted in pulmonary hypertension within 14 days. These morphologic, biochemical, and hemodynamic changes are nearly identical to alterations induced by the parent alkaloid, MCT. PMID- 2256111 TI - Cyanide-induced alteration of cytosolic pH: involvement of cellular hydrogen ion handling processes. AB - Neuronal cells exposed to cyanide rapidly lose the capacity to regulate internal Ca2+ homeostasis, thereby accumulating an excess cytosolic Ca2+ load. The present study was undertaken to examine the effects of KCN on another important ion: hydrogen ion. KCN (1-10 mM) rapidly decreased intracellular pH (pHi) of cultured pheochromocytoma (PC12) cells as indicated by the pH-sensitive fluorescent dye 2',7-bis(carboxyethyl)-5(6)-carboxyfluorescein. Removal of Ca2+ from the media or pretreating the cells with diltiazem (10(-5) M), a calcium channel blocker, delayed the onset and reduced the magnitude of the drop in pHi. Lowering the pH of the incubation medium (pHo) to 6.9 exaggerated the drop in pHi, while raising it to 7.9 attenuated the change in pHi. Removal of Na+ from the media enhanced the cyanide effect. Reintroduction of Na+ or substitution with Li+ reversed the cytosolic acidification, suggesting involvement of the Na+/H+ exchanger in the cyanide action. Pretreatment of cells with amiloride, 0.2 mM, blunted the cytosolic acidification induced by KCN, possibly by decreasing intracellular Na+ accumulation and disrupting H+ efflux. Cyanide thus produces a rapid dysfunction of hydrogen ion handling mechanisms and this may play a role in cyanide neurotoxicity. PMID- 2256112 TI - Studies on the mechanisms of Ni2(+)-induced cell injury: I. Effects of Ni2+ on microtubules. AB - Cytoskeletal perturbations have been associated with exposures to a variety of toxic agents as well as a number of human pathological conditions. We have observed dramatic alterations in the organization of microtubules (MT), a major component of the cytoskeleton, in 3T3 cells exposed to Ni2+. Severe perinuclear bundling and aggregation of MT occurred in both a time- and dose-dependent fashion, and this MT damage was reversible upon removal of Ni2+ from the culture media. To understand the mechanism of the Ni2(+)-induced MT change, we investigated the effect of Ni2+ (0.01 to 3.0 mM) on in vitro tubulin polymerization. Ni2+ at lower concentrations (0.01 to 1.0 mM) had little or no significant effect on the kinetics of MT polymerization. In contrast, in the presence of 1.5 to 2.0 mM Ni2+, a significant promoting effect on both the rate and the final extent of polymerization was observed. However, at Ni2+ concentrations higher than 2.0 mM, such stimulatory effect on the rate and the final extent of tubulin polymerization declined. Furthermore, the promoting effects of Ni2+ on MT polymerization were accompanied by a significant decrease in the lag period. Electron microscopic examination of samples of the polymerization product showed that MT, polymerized in the presence of 2.0 mM Ni2+, appeared more numerous and shorter (1.10 +/- 1.02 microns) than those of control (3.81 +/- 2.29 microns; p less than 0.005). This was probably a direct result of an increase in the number of initiation centers in the presence of Ni2+ as a consequence of the decreased critical concentration (7%, p less than 0.05) necessary for polymerization to occur. Our results suggest that Ni2+ may exert its toxic effect on MT in cultured cells by altering the normal kinetics of MT polymerization. PMID- 2256113 TI - Deposition of ultrafine aerosols in rat nasal molds. AB - To evaluate the health effects of air pollutants on the respiratory tract, it is critical to determine the regional deposition of inhaled aerosols. Information on deposition of larger particles (greater than 0.2 microns) in the nasal passages of laboratory animals is available; the deposition fraction increases with increasing particle size. However, little deposition information is available for ultrafine particles of less than 0.2 microns. Three clear, plastic molds (models) of the nasal passages of F344/N rats, prepared from metal replica casts were used in these studies. Total deposition of ultrafine aerosols in the casts was determined by using a unidirectional flow system. The pressure drops measured in the casts were a function of flow rate to the power of 1.4-1.6, indicating that flow through the nasal passages has nonlaminar components. Deposition data were obtained by using monodisperse sodium chloride aerosols with particle sizes ranging from 0.2 to 0.005 microns, at inspiratory and expiratory flow rates of 200 to 600 ml/min. Similar deposition data were obtained for two of the casts studied. Deposition efficiency was greatest for the smallest particles, and decreased with increasing particle size and flow rate. At an inspiratory flow rate of 400 ml/min, which is comparable to the mean respiratory flow of an adult male F344 rat with a respiratory minute volume of 200 ml, deposition efficiencies reached 40 and 70% for 0.01- and 0.005-microns particles, respectively. These studies demonstrated that turbulent diffusional deposition was the dominant mechanism for uptake of ultrafine particles by the nasal passages. PMID- 2256114 TI - Accumulation of inorganic mercury along the renal proximal tubule of the rabbit. AB - The purpose of the present study is to characterize the accumulation of inorganic mercury along the proximal tubule of the rabbit. New Zealand white rabbits were given a 0.5 mumol/kg dose of mercuric chloride along with 150 microCi of 203Hg. Forty-eight hours after the animals had been treated, individual segments of the nephron were obtained by microdissection. The segments of the nephron were measured in length and then were counted in a gamma counter to determine the percentage of the administered dose of inorganic mercury that had accumulated in them. There was significant accumulation of mercury along the proximal tubule during the 48 hr after the dose of mercuric chloride was administered. The S1 segment of the proximal tubule accumulated 0.000226 +/- 0.000031% (mean +/- SE) of the administered dose of inorganic mercury per millimeter tubule. The amount of mercury that accumulated in the S2 segment of the proximal tubule was similar to that in the S1 segment. By contrast, only half as much inorganic mercury accumulated in each millimeter of the S3 segment of the proximal tubule. No significant accumulation of inorganic mercury could be detected in pooled samples of various segments of the distal nephron. The findings in the present study indicate that the renal accumulation of inorganic mercury in the rabbit occurs mainly as a result of the accumulation of the metal in the proximal tubule, with the accumulation predominating in the S1 and S2 segments. PMID- 2256115 TI - Acute exposure to tris(2-chloroethyl)phosphate produces hippocampal neuronal loss and impairs learning in rats. AB - Adult female, Fischer-344 rats were exposed to 275 mg/kg of tris(2 chloroethyl)phosphate (TRCP) by gavage. TRCP produced consistent signs of convulsive activity within 60-90 min after dosing and extensive loss of CAT hippocampal pyramidal cells when examined 7 days after dosing. At the light microscopic level, toxic effects of TRCP on pyramidal cells in the CA3 and CA4 regions and on granule cells in the dentate gyrus were less severe than those on the CA1 cells. The seizure-related and neurohistological effects of TRCP were significantly attenuated by pretreatment with atropine or chlordizepoxide, suggesting that the hippocampal damage was related to the seizures produced by TRCP. In a second experiment designed to assess the potential health risk associated with TRCP, exposed rats were mildly impaired in the acquisition of a reference memory task in a water maze. However, TRCP-exposed rats were consistently impaired in performing a repeated acquisition task in the water maze. These data underscore the potential health risk associated with exposure to TRCP and support the conclusion that the hippocampus is intimately involved in spatial memory in rats. PMID- 2256116 TI - Lead impairs the production of osteocalcin by rat osteosarcoma (ROS 17/2.8) cells. AB - The serum level of osteocalcin, a bone-specific protein produced by osteoblasts and an index of bone formation, is decreased in lead-intoxicated children. To elucidate the effect of lead on the hormonal regulation of osteocalcin production, ROS 17/2.8 cells were treated with 0, 5, 10, or 25 microM lead acetate for 24 hr, followed by an additional 24-hr lead treatment with or without 100 pg 1,25-dihydroxyvitamin D3/ml medium. At the end of this period a radioimmunoassay was conducted to determine the amount of osteocalcin present in the cells and secreted into the medium. 1,25-Dihydroxyvitamin D3 increased osteocalcin secretion in control cultures, but this increase was prevented by lead in a concentration-dependent manner. Osteocalcin secretion by cultures treated with 10 or 25 microM lead was even lower than in cultures not stimulated with 1,25-dihydroxyvitamin D3. Intracellular levels of osteocalcin were slightly elevated with 1,25-dihydroxyvitamin D3, and there was no lead effect on cellular levels. These data indicate that lead attenuates basal and 1,25-dihydroxyvitamin D3-stimulated production of osteocalcin in ROS 17/2.8 cells. Because osteocalcin appears to play a central role in bone mineralization, altered osteocalcin production may be a key event in the skeletal toxicity of lead. PMID- 2256117 TI - The in vitro effects of four isomers of dinitrotoluene on rat Sertoli and Sertoli germ cell cocultures: germ cell detachment and lactate and pyruvate production. AB - The present study was undertaken to evaluate the in vitro effects of four isomers of a known testicular toxicant, dinitroluene (DNT). Rat Sertoli or Sertoli-germ cell cocultures were treated, after 3 days in culture, with DNT isomers (0.01 to 100 microM) or 1,3-dinitrobenzene (1,3-DNB) for 24 hr. Cellular morphology, germ cell detachment (GCD) and lactate pyruvate production were used as sensitive effect markers of in vitro toxicity. Morphologically the Sertoli cell monolayer remained intact 24 hr after exposure to DMSO, 1,3-DNB, or DNT isomers. Some apparent cytotoxicity was observed at 100 microM 3,4-DNT: the monolayer was disrupted with extensive vacuolation of the Sertoli cells. Cocultures treated with concentrations of 50 microM DNT isomers closely resembled cells treated with 100 microM 1,3-DNB. GCD increased in a dose-dependent manner (0.01 and 10 microM DNT isomers) increasing between 2- and 10-fold over control. Both lactate and pyruvate production increased with rising concentrations of DNT isomers. The most sensitive effect was seen with 3,4-DNT (10 to 25 microM). In the case of 2,6-DNT, despite increases in GCD and lactate production, only a minimal increase in pyruvate was demonstrated. Overall, the ratio of lactate to pyruvate production declined with increasing doses of DNT. These results indicate that the four isomers of DNT directly affected Sertoli cell morphology and function, effects comparable to those seen with the Sertoli cell toxicant 1,3-DNB. Further, the data support the hypothesis that DNT may be a Sertoli cell toxicant. PMID- 2256118 TI - Physiologically based pharmacokinetic and pharmacodynamic model for the inhibition of acetylcholinesterase by diisopropylfluorophosphate. AB - Organophosphate (OP) exposure can be lethal at high doses while lower doses may impair performance of critical tasks. The ability to predict such effects for realistic exposure scenarios would expedite OP risk assessment. To this end, a physiologically based model for diisopropylfluorophosphate (DFP) pharmacokinetics and acetylcholinesterase (AChE) inhibition was developed in mammals. DFP tissue:blood partition coefficients, rates of DFP hydrolysis by esterases, and DFP-esterase bimolecular inhibition rate constants were determined in rat tissue homogenates. Other model parameters were scaled for rats and mice using standard allometric relationships. These DFP-specific parameter values were used with the model to simulate expected in vivo pharmacokinetic data from mice and rats. Literature data were used for model validation. DFP concentrations in mouse plasma and brain were successfully simulated after a single iv injection (B.R. Martin, 1985, Toxicol. Appl. Pharmacol. 77, 275-284). AChE inhibition and AChE resynthesis data from this study were also simulated. Effects of repeated, subcutaneous DFP dosing on AChE activity in rat plasma and brain (H. Michalek, A. Meneguz, and G.M. Bisso, 1982, Arch. Toxicol., Suppl. 5, 116-119; M.E. Traina and L.A. Serpietri, 1984, Biochem. Pharmacol. 33, 645-653) were also simulated well, but the return of brain AChE activity to basal levels after cessation of repeated dosing was not as well described. The initial model structure returned brain AChE activity to the original level, while in the laboratory studies brain AChE never returned to basal levels, even at 35 days after the last dose. These data suggest modulation of AChE synthesis with prolonged DFP exposure. This study demonstrated the possibility of using a model based on mammalian physiology and biochemistry to simulate in vivo data on DFP pharmacokinetics and AChE inhibition. Scaling of the model between rats and mice was also successful. The approach holds promise for predictive simulation of organophosphate-mediated AChE inhibition in humans. PMID- 2256120 TI - Lead-induced behavioral impairment on a spatial discrimination reversal task in monkeys exposed during different periods of development. AB - A total of 52 monkeys (Macaca fascicularis) were dosed orally with vehicle or 1.5 mg/kg/day of lead on one of four dosing regimens (13 monkeys/group): Group 1, vehicle only; Group 2, dosed with lead from birth onward; Group 3, dosed with lead from birth to 400 days of age and vehicle thereafter; Group 4, dosed with vehicle from birth to 300 days of age and lead thereafter. Blood lead concentrations averaged 3-6 micrograms/dl when monkeys were not being dosed with lead, 32-36 micrograms/dl when being dosed with lead and having access to infant formula, and 19-26 micrograms/dl when being dosed with lead after weaning from infant formula. When monkeys were 7-8 years old, they were tested on three spatial discrimination reversal tasks: no irrelevant cues, irrelevant form cues, and irrelevant form and color cues. Fifteen reversals were run for each task. Only Group 2 was impaired in the absence of irrelevant cues, while all three treated groups were impaired in the presence of irrelevant cues. These results are in contrast to results from a series of nonspatial discrimination reversal tasks in these monkeys in which Groups 2 and 4 were impaired and Group 3 was unimpaired. The present results are in agreement with results from another spatial task, delayed alternation, in which all three treated groups were impaired. PMID- 2256119 TI - Histochemical localization of formaldehyde dehydrogenase in the rat. AB - Formaldehyde dehydrogenase (FDH) activity has been demonstrated biochemically in the olfactory and respiratory mucosae and in the liver of the rat, but the cellular localization of this enzyme has not been investigated. A histochemical procedure was developed to permit cellular localization of FDH. This allowed us to examine the relationship between distribution of FDH and formaldehyde-induced toxicity. Cold-processed glycol methacrylate embedded tissues were used to localize FDH activity in the rat respiratory tract, kidney, liver, and brain. Five- or ten-micrometer tissue sections were incubated in a reaction mixture containing formaldehyde (HCHO), glutathione (GSH), NAD+, nitroblue tetrazolium, pyrazole, and disulfiram. A blue formazan precipitate was formed at the site of FDH activity. Epithelial cell cytoplasm of both the respiratory and the olfactory mucosae of the nose stained for FDH, and olfactory sensory cell nuclei were also positive. Underlying Bowman's and seromucous glands were weakly positive. The lung had FDH activity located mainly in the Clara cells of the airways, with only diffuse weak activity in the lung parenchyma. Liver had activity in the cytoplasm of the hepatocytes, while in the kidney FDH was most prominent in the brush border of the P2 segment of the proximal tubules. Brain white matter stained strongly for FDH, while in gray matter only the neuropil exhibited weak activity. Corresponding tissue sections were stained for sulfhydryls; these sections indicated that GSH is likely to be present in all cells with FDH activity. For the respiratory tract these results demonstrate distinct differences between the location of FDH activity and previously reported nonspecific aldehyde dehydrogenase activity in the nose (M. S. Bogdanffy, H. W. Randall, and K. T. Morgan, 1986, Toxicol. Appl. Pharmacol. 82, 560-567). While high aldehyde dehydrogenase activities were found in tissues with low toxicities due to acetaldehyde exposure and vice versa, FDH activity was observed in tissues whether or not they exhibited a toxic response to inhaled HCHO. While not able to account for the localized toxicity of HCHO, the presence of FDH and glutathione in the epithelial layer of the nasal cavity presents a barrier to inhaled formaldehyde at low concentrations and may partially explain the observed nonlinearity of HCHO toxicity. PMID- 2256121 TI - Comparison of the hematologic effects of 2-butoxyethanol using two types of hematology analyzers. AB - Earlier reports from this laboratory indicated that 2-butoxyethanol (BE) causes acute hemolytic anemia in rats as evidenced by a time- and dose-dependent decrease in the number of red blood cells, in hemoglobin concentrations, and in hematocrits (HCT). Subsequent studies showed that treatment with BE causes an early increase in HCT and mean cell volume (MCV). Since this effect went undetected in our early work and resulted in the publication of inaccurate information, present studies were designed to reinvestigate the hematologic effects of BE using the laser-based hematology analyzer which was used in the early studies and an impedance-based hematology analyzer, simultaneously. Packed cell volumes (PCV; spun HCT) were also performed on all blood samples. Male F344 rats were treated with 0, 125, 250, or 500 mg BE/kg (po) and blood was collected from the retro-orbital venous plexus at 1, 2, 4, 8, and 24 hr after dosing. Hematology profiles of BE-treated rats obtained from the impedance-based analyzer showed an early dose- and time-dependent increase in HCTs and MCVs. In contrast, analysis of the same blood samples using the laser-based analyzer showed a dose- and time-dependent decrease in HCTs with little or no change in MCVs. Changes observed in PCVs were consistent with results obtained from the impedance-based analyzer. Therefore, under the experimental conditions of this and previous studies, the laser-based analyzer was unable to detect early increases in HCTs and MCVs in rats treated with BE. Finally, these data explain the different principles utilized to measure cell size by both instruments as they relate to the hematologic effects of BE. Moreover, present data show that BE-induced hemolysis of erythrocytes is preceded by a quantitatively unique and massive swelling suggesting the erythrocyte membrane as the target. PMID- 2256122 TI - Early loss of large genomic DNA in vivo with accumulation of Ca2+ in the nucleus during acetaminophen-induced liver injury. AB - Hepatotoxic doses of acetaminophen cause early impairment of Ca2+ homeostasis in the liver. This in vivo study considers the nucleus as a possible site of lethal Ca2+ action by evaluating whether acetaminophen raises Ca2+ in this compartment, whether DNA becomes altered, and whether DNA changes occur early enough during injury to contribute causally to necrosis. Fed Swiss mice were treated with 600 mg/kg acetaminophen ip and livers and blood samples were collected over time. Total nuclear Ca2+ accumulation and fragmentation damage to DNA showed modest parallel increases between 2 and 6 hr, followed by greater than 200% rises at 12 hr mirroring the appearance of frank liver injury (ALT greater than 10,000 U/liter). However, agarose gel electrophoresis revealed extensive loss of large genomic DNA from 2 hr onward, accompanied by the appearance of periodic DNA fragments. Thus, acetaminophen raised nuclear Ca2+ concentrations and promoted DNA fragmentation in vivo. The considerable cleavage of DNA seen at late times probably resulted from cell death, whereas loss of large genomic DNA from 2 hr onward appeared at an early enough point in time to be a contributing factor in acetaminophen-induced liver necrosis. PMID- 2256123 TI - Changes in the expression of the cholinergic structures of human T lymphocytes due to maturation and stimulation. AB - We demonstrated that thymocytes have significantly lower AChE activity, no mAChR binding capacity and the same nAChR binding value, that we can measure on PBLs. The expression of all these structures was changed due to mitogenic stimulation. There is a strong evidence that cholinergic modulation may play a role in T-cell differentiation. PMID- 2256124 TI - Early expression of histocompatibility class I, class II and myeloid antigens on human fetal liver cells. PMID- 2256125 TI - Characterization of intrathymic and extrathymic T cell development in spontaneous thymoma Buffalo/Mna rats. AB - The developmental status of T cell lineages at prethymic, intrathymic and postthymic stages in spontaneous thymoma Buffalo/Mna (BUF/Mna) rats was characterized on the basis of surface phenotypes and some immune responses. The proportion of bone marrow cell populations was shown to be normal in thymoma rats by immunofluorescence flow cytometry (FACS). In spite of a cortex-predominant appearance of thymomas, the proportion of thymocyte populations was phenotypically normal as assessed by FACS. Double immunohistochemical stainings revealed that a substantial number of single-possible (CD4+CD8- or CD4-CD8+) thymocytes existed not only in the narrowed medullary areas but also in the enlarged cortical areas of the thymomas. In lymph nodes, the proportion of T cells increased with age, reaching 88% after 20 months of age. This increase was due mainly to an increase in the CD8+ population but not the CD4+ population, resulting in low CD4/CD8 ratios. An abnormal increase of Thy1+ immature T cells was also observed in the lymph nodes. However, these phenotypic changes in the T cell lineages in the thymoma rats were not so influential as to alter their immunological reactivities, such as the primary antibody response to a T dependent antigen, the graft-versus-host reaction and the mixed lymphocyte reaction to allo-antigens. These results suggest the possible presence of some altered differentiation pathways for intrathymic and postthymic T cell development in BUF/Mna rats. PMID- 2256126 TI - Limiting dilution analysis of ontogeny of self- and allo-reactive thymocytes of C57BL/6J mouse. AB - In the present study, functional development of mouse fetal through neonatal to adult thymocytes was analyzed by limiting dilution assay (LDA) in terms of allo reactivity and self-reactivity. Self-reactive PTL-p were always much less than those of allo-reactive PTL-p at all ages examined in this study. These results imply that thymocyte proliferation is not predominantly driven by responses to self antigens in the thymus, and that self-reactive thymocytes do not develop prior to allo-reactive thymocytes during thymic ontogeny. It is unlikely that most of such proliferating, murine early fetal thymocytes are self-reactive; allo reactive cells are unlikely to have been derived from self-reactive cells during T cell development. PMID- 2256127 TI - Commentary on the biological self: Toward a "Biological Ego". From Garrod's "chemical individuality" to Burnet's "self". AB - Starting from the conceptual premises of Garrod, who as long ago as 1902 spoke of "chemical individuality", and of Burnet (1949), who recognized as self one's own molecular antigenic structures (as opposed to the antigenic "alien": the non self), the discovery and understanding of HLA antigens and of their extraordinarily individual and differentiated polymorphisms have gained universal recognition. Transplant medicine has now dramatically stressed, within man's knowledge of himself, the characteristic of his "biological uniqueness". Today man, having become aware of being a biological antigenic-molecular individuality which is unique and different from that of all of his fellow men (except for monozygotic twins), can therefore easily consider himself a true "biological Ego". PMID- 2256128 TI - Motivating your OR staff: keeping the enthusiasm alive. PMID- 2256129 TI - Double duty. Using the laser log as a quality assurance tool. AB - 1. Analysis of the information contained in the laser log allows for the development of an educational program based on specific needs. 2. The problem for many laser nurses is how to design a laser log so it can be used as an efficient quality assurance tool. 3. To design an efficient log, one must first consider what aspects of the laser program need evaluation and then develop a log accordingly. 4. A laser education program can be tailored to specific needs as determined by an analysis of the laser use in the operating room. PMID- 2256130 TI - The other side of the phone. Sales representatives in the OR. AB - 21. There are certain expectations that salespersons need to be aware of to have continued business, quality time, and an invitation to return to the surgery department. 2. It is important to know that even competitive institutions have their channels of communication open about products, equipment, and dependability of the sales representatives. 3. Not all companies offer appropriate training to prepare their sales representatives for the operating room. 4. Sales representatives need to remember that admission to the operating room is a privilege, not a right, and privileges can be revoked. PMID- 2256131 TI - Stockless inventory: supplies of the future. PMID- 2256133 TI - The art of motivation. PMID- 2256132 TI - The difficult doctor. AB - Nurses in the operating room may find themselves in interpersonal conflict with difficult doctors. It is important to remember that the relationship may be influenced by patterns of thinking and behavior learned in childhood, in one's culture, and through the professional socialization and education process. The nurse may be able to improve communication by assessing the difficult doctor's interaction, using approaches that will elicit cooperation, timing approaches strategically, avoiding approaches that will precipitate defensiveness, and using direct approaches. PMID- 2256134 TI - Interpleural catheters for postoperative analgesia: perioperative considerations. PMID- 2256135 TI - ZIFT: new hope for infertile couples. PMID- 2256136 TI - Maximizing wound healing with silver-impregnated porcine xenograft. AB - 1. Grossly contaminated or chronically infected wounds require adequate debridement of dead tissue and wound coverage or closure. 2. Porcine xenograft is a temporary wound covering that prevents evaporation and thereby creates an environment for new cells to propagate instead of being sacrificed by desiccation. 3. The addition of silver ions to the porcine xenograft provides a potent antimicrobial agent that is only active at the surface where it is needed, has no systemic effects, and allows epithelialization to proceed in half the time of uncovered or unsilvered methods. 4.Silver-impregnated porcine xenograft provides a temporary wound covering that is antimicrobial, physiologic, and allows even the most massive and chronically contaminated wounds of years duration to be healed by careful, consistent dressing changes without skin grafts or flaps. PMID- 2256137 TI - Never knowing one's place: Temple University School of Medicine and the medical education hierarchy. PMID- 2256138 TI - William Scott Wadsworth: an appreciation of an anomalous career. PMID- 2256139 TI - The need for care: families, patients, and staff at a nineteenth-century insane asylum. PMID- 2256140 TI - "Dearest Maria": letters from a medical student in Philadelphia to his fiancee, 1845-1846. PMID- 2256141 TI - Philadelphia health care photographs: a partial guide to archival holdings. PMID- 2256142 TI - The effect of individual HLA-A and -B mismatches on the generation of cytotoxic T lymphocyte precursors. AB - In order to study the correlation between HLA mismatches and the cytotoxic T lymphocyte precursor frequency, we used a limiting dilution analysis to determine the CTLp frequencies against individual mismatched HLA-A and -B alloantigens in 21 patients waiting for a renal transplant. Altogether, thirty-three mismatched HLA-A antigens and 55 HLA-B antigens were tested. The CTLp frequencies against mismatches of HLA-B locus antigens were found to be significantly higher than those against HLA-A antigens (P less than 0.002). This may explain why matching for HLA-B antigens is more important for a good renal allograft survival than matching for HLA-A antigens. PMID- 2256143 TI - Nuclear magnetic resonance of hepatic graft-versus-host disease in mice. AB - The liver is a major target organ of graft-versus-host disease. We have induced graded intensities of acute GVHD to minor histocompatibility antigens in a well characterized murine bone marrow transplant model and analyzed hepatic pathology one month after BMT. Nuclear-magnetic-resonance relaxation times and proton spectra were compared to systemic clinical disease, serum biochemistries, and histologic findings. T2 relaxation times correlated directly with the intensity of histologic abnormalities, but the hepatic histology remained mild even in animals with moderate GVHD. In contrast, NMR proton spectra of hepatic tissue showed large decreases in metabolite levels (acetate and glycogen) in animals with moderate systemic disease despite mild hepatic histology. We conclude that NMR of the liver can be used to differentiate hepatic from systemic GVHD in this model and may help to elucidate the differential effects of GVHD in various target organs. PMID- 2256144 TI - Adjuvant radiochemotherapy following orthotopic liver transplantation for bile duct cancer. PMID- 2256145 TI - Treatment of Wegener's granulomatosis after renal transplantation: is cyclosporine the preferred treatment? PMID- 2256146 TI - Protective effects of liver transplantation on a simultaneously transplanted kidney in a highly sensitized patient. PMID- 2256147 TI - Bone marrow aspiration as a diagnostic tool for acute toxoplasmosis in a kidney transplant recipient. PMID- 2256148 TI - Venous reconstruction of pediatric en-bloc kidneys for transplantation. PMID- 2256149 TI - Recurrence of lupus nephritis in a renal allograft with histologic transformation of the lesion. PMID- 2256150 TI - Long-term improvement in renal function using nifedipine in cyclosporine associated hypertension. PMID- 2256152 TI - Downregulation of antidonor cytotoxic lymphocyte responses in recipients of donor specific transfusions. PMID- 2256151 TI - A prospective study of prophylactic ATG versus cyclosporine in regrafted and highly sensitized renal allograft recipients. PMID- 2256153 TI - A comparative study of donor-specific transfusions administered at weekly and two weekly intervals. PMID- 2256154 TI - Induction of unresponsiveness to rat hepatic allografts by pretreatment with donor splenocytes and peritransplant cyclosporine. PMID- 2256155 TI - Absolute specificity of neonatally induced transplantation tolerance. PMID- 2256156 TI - Mechanisms maintaining antibody-induced enhancement of allografts. III. Examination of graft-versus-host reactivity of T cell subsets from rats with long surviving grafts. PMID- 2256157 TI - The effect of TLI and cyclosporine on xenograft survival. PMID- 2256158 TI - Survival of neonatal mouse epidermal allografts. PMID- 2256159 TI - A new cyclosporine formulation. PMID- 2256160 TI - Prolongation of adult skin allograft survival by cotransplantation of neonatal skin in antilymphocyte serum and donor bone marrow cell-treated mice. AB - Adult male B6AF1 (H-2KIb/kDb/d) mice were given skin allografts from adult male C3H (H-2k) mice, with and without contralateral cotransplants. The cotransplants were of either adult or neonatal (less than 24 hr) C3H skin. In recipient mice treated peritransplantation with antilymphocyte serum and posttransplantation with an i.v. injection of donor-strain bone marrow cells, the presence of a neonatal cotransplant resulted in significantly longer survival of the adult grafts. Median survival time (MST) for adult grafts, for the group that received a neonatal cotransplant was greater than 100 days, in comparison to MSTs of 59 days and 55 days for the groups that received only single adult grafts or the adult graft with an adult cotransplant. These results suggest an active immunomodulatory contribution of neonatal tissue, and we term this phenomenon the "cotransplant effect." This prolongation of survival of the adult grafts by the neonatal cotransplants was statistically significant in animals treated with ALS and BMC, but not in recipients that were treated with ALS only (MST = 34 days, in comparison with 29 days for groups that received either a single adult graft or an adult graft with an adult cotransplant). The graft-prolonging effects of an infusion of donor BMC thus appear to potentiate the expression of the cotransplant effect. An understanding of this effect may lead to improved methods of controlling the allograft response to adult tissues in the clinical setting. PMID- 2256161 TI - In vitro and in vivo effects of monoclonal antibodies against T cell subsets on allogeneic and xenogeneic responses in the rat. AB - The Syrian hamster-to-rat represents an example of a concordant species difference, and therefore organ transplants using the hamster as the donor and the rat as the recipient are not rejected hyperacutely, as in discordant species combinations. Cellular mechanisms of xenogeneic rejection of hamster hearts by rats were studied both in vitro and in vivo, using monoclonal antibodies to rat T cell antigens. The results of this study reveal that CD4-positive cells of rats proliferated in vitro to both allogeneic stimulators and xenogeneic stimulators from a concordant strain, but required accessory cells of the responder phenotype to proliferate to discordant human stimulators. Monoclonal antibody therapy was used to prevent graft rejection in allogeneic and xenogeneic species combinations, using the rat as the recipient. Treatment with anti-CD4 antibodies was effective in prolonging allograft survival across a full MHC mismatch. No rejection occurred during antibody therapy, and long-term graft survival was achieved in 1/3 of transplanted grafts. The same monoclonal antibody therapy led to increased survival of grafts from hamster donors, but all of these grafts were rejected during therapy, and no long-term graft survival was achieved. Anti-CD8 antibody therapy, combined with anti-CD4 did not improve survival of hamster hearts in rats. Addition of cyclosporine to the anti-CD4 regimen also did not improve graft survival. Injection of an anti-T cell receptor antibody was no better than the anti-CD4 antibody in prolonging the survival times of heart grafts from the concordant xenogeneic species. These data suggest that the rejection of concordant xenogeneic tissue is not wholly a T cell-dependent phenomenon. PMID- 2256162 TI - The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat. AB - To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation. PMID- 2256163 TI - Small bowel transplantation in rats. The effect of pretransplant donor-specific blood transfusions on various segments of small bowel grafts. AB - The effects of pretransplant donor-specific blood transfusion on the survival of orthotopic small bowel transplants in rats were investigated in the fully allogeneic BN (Rt1n) to WAG (Rt1u) donor-host combination. Previous studies show that in this combination DSTs lead to permanent survival of heterotopically transplanted hearts, marked prolongation of kidney grafts, and moderate prolongation of pancreas grafts but have no effect on skin grafts. Without pretreatment, total small bowel grafts (+/- 45 cm) were rejected in 12.2 +/- 1.8 days (mean +/- SD), and 10-cm segments of jejunum or ileum in 11.2 +/- 4.0 and 11.6 +/- 0.5 days, respectively. Three DSTs given on days -21, -14, and -7 before transplantation had no effect on graft survival in any of the groups tested. Total small bowel grafts were rejected in 12.8 +/- 2.5 days, and 10-cm-long segments or jejunum or ileum in 17.0 +/- 7.2 days and 11.5 +/- 2.7 days, respectively. Graft-versus-host disease, which was mild and transient, occurred in 50% of the nontreated rats engrafted with a total small bowel, in 40% of the animals transplanted with an ileum segment, and in none of the rats that received a jejunal transplant. In the DST-pretreated groups, none of the animals transplanted with a total small bowel or ileum segment and 16.6% of the animals transplanted with a jejunum segment showed clinical signs of GVHD. When DST pretreatment was combined with cyclosporine, grafts did not survive any longer than with cyclosporine treatment alone. It is concluded that DSTs ameliorate GVHD but do not prolong the survival of small bowel allografts nor act additively with cyclosporine treatment. PMID- 2256164 TI - Angiogenic peptides in pancreatic islet transplantation to diabetic rats. AB - To overcome the deleterious effects of hyperglycemia on islet transplantation, we have used recombinant basic fibroblast growth factor (FGF), an angiogenic peptide, concurrently with the intrasplenic placement of neonatal islets in severely diabetic rats. In both experimental and control rats, a minipump, secured to the spleen with a small indwelling catheter, delivered either the basic FGF at 10 ng/hr, or only the diluent. The rate of cure in the animals receiving the islets plus the peptide was significantly higher (70%) than in control rats (20%). This difference (P less than 0.05), could not be attributed to direct effects of the peptide on islet function or to increased islet cell replication. We believe that these results may be best explained as an enhancement by basic FGF of the angiogenic process in the transplant islets. PMID- 2256165 TI - Protective effects of trifluoperazine on the microcirculation of cold-stored livers. AB - Previous studies have shown a protective effect of trifluoperazine (TFP), a calmodulin inhibitor, upon the microcirculation of cold-stored kidneys. The present study points to similar beneficial effects of TFP on the microcirculation of cold-stored livers; 25 canine livers were preserved for 24 hr with Euro Collins' solution (EC) (n = 8), University of Wisconsin solution (UW) (n = 7), or UW + TFP (n = 10). The stored livers underwent heterotopic transplantation (HLTX); hepatic-artery and portal-vein pressure and flow were monitored; oxygen consumption and extraction were measured before HLTX and at 15-min intervals after reperfusion, for 1 hr. Mean hepatic-artery and portal-vein flow (HAF & PVF) prior to donor hepatectomy were 172 and 530 cc/min, respectively. Poor HAF and PVF occurred in EC-HLTX (mean 35, 175 cc/min, respectively). The damaged EC flushed livers could not compensate to the decreased hepatic blood flow by increased oxygen extraction (oxygen consumption and extraction, 8.7 vol.% and 48%, respectively). Light and electron microscopy showed severe liver necrosis and periportal hemorrhages. Improved hepatic-artery and portal-vein flows were seen in UW HLTX (105 and 254 cc/min), and oxygen consumption and extraction were 16.4 vol.% and 66%, respectively. Liver biopsy taken just before reperfusion revealed well-preserved liver architecture. Liver biopsy obtained 1 hr after reperfusion revealed marked edema of the portal triad, sinusoid congestion, and hemorrhage. Electron-microscopy biopsies obtained during reperfusion at 15-min intervals revealed severe vasospasm of the terminal hepatic arterioles and progressive damage to the liver microcirculation. The addition of TFP to the UW flush solution resulted in excellent protection of the liver microcirculation. Marked increase in hepatic-artery and portal-vein blood flow was noted after reperfusion (mean 167 and 421 cc/min, respectively (P 0.02 vs. UW: P 0.001 vs. EC). The recovery of metabolic activity was evident by the high oxygen consumption and extraction (25.8 vol.% and 80%, respectively). And serial liver biopsies obtained after reperfusion have shown excellent protection of liver architecture and the absence of hepatic arteriolar vasospasm. Taken together, these data suggest that the addition of TFP to the UW solution protects the liver microcirculation by rendering the hepatic microcirculation insensitive to vasospastic stimuli during reperfusion, thus permitting better metabolic recovery after transplantation. PMID- 2256166 TI - Evaluation of preservation damage after porcine liver transplantation by assessment of hepatic microcirculation. AB - The ischemic damage following liver transplantation (LTX) is predominantly located at the endothelial cell level and is a major cause for a disturbance of microcirculation. The present study was designed to test the hypothesis that changes in the quality of organ preservation are correlated with changes in microcirculation: 16 pigs underwent LTX, preservation by Bretschneider's HTK solution (Histidin, Tryptophan, alpha-Ketoglutarat) complemented by indomethacin (50 mumol/L). Cold ischemia times were 9 hr (n = 8) and 18 hr (n = 8), respectively. Using the H2-clearance technique, hepatic microcirculation was measured before, 30 min, and 20 hr after LTX. Normal tissue perfusion was 107 +/- 16 ml/100 g/min, at 30 min posttransplantation 91 +/- 13 ml/100 g/min in the short-term and 48 +/- 7 ml/100 g/min in the long-term preservation group. Whereas no animal of the long-term preservation group survived longer than 8 hr, all animals of the short-term preservation group survived, and tissue perfusion could be measured 20 hr postoperatively (101 +/- 19 ml/100 g/min). At 30 min postoperatively, all surviving animals had tissue perfusion rates greater than 70, and all nonsurvivors had values below 60 ml/100 g/min. We conclude therefore that the extent of decrease of microcirculation after LTX may be a useful predictor of organ function and survival. PMID- 2256167 TI - The effects of fasting on the quality of liver preservation by simple cold storage. AB - Although livers can be successfully preserved for 24 hr or more, often the transplanted livers have poor or no (primary nonfunction) function. The quality of the liver does not appear dependent upon the time of preservation but may be dependent upon the condition of the donor. In this study we have investigated the effects of fasting on the quality of livers for transplantation. Rabbits were fasted (48 hr) and livers preserved in the UW solution for 6-8 hr. Functions of the liver were analyzed by isolated perfusion for 2 hr. Also, pigs were fasted for 72 hr, livers preserved for 12 hr, and viability determined by orthotopic transplantation. Fasting depleted the liver glycogen by 85% but had no effect on ATP or glutathione concentrations. Rabbit livers from fasted animals produced similar amounts of bile, released similar concentrations of lactate dehydrogenase (LDH) and aspartate amino transaminase (AST) into the perfusate, maintained similar concentrations of ATP and glutathione in the tissue, and had a similar intracellular K:Na ratio after 24-hr preservation when compared to livers from fed animals. After 48-hr preservation, livers from fasted animals were less viable than livers from fed animals, including: reduced bile production (2.0 +/- 0.3 vs. 5.0 +/- 0.9 ml/2 hr, 100 g), greater release of LDH (3701 +/- 562 units vs. 1123 +/- 98 units) and AST, less ATP (0.326 +/- 74 vs. 0.802 +/- 160 nmol/g), less glutathione (0.303 +/- 13 vs. 0.933 +/- 137 nmol/g), and a lower K:Na ratio (1.5 +/- 0.9 vs. 7.4 +/- 0.6). Pigs receiving livers from fed animals preserved for 12 hr had better survival (5/6, 83%) than livers from fasted animals (3/6, 50%). The results show that the nutritional status of the donor can affect the outcome of liver preservation and transplantation. Increased injury in livers from fasted animals may be due to the loss of glycogen that may be an essential source of energy in the initial posttransplant period. In clinical liver transplantation the nutritional status of the donor may be an important factor in the initial function of the liver, and methods to increase the nutritional status of the donor may be important in increasing the quality of livers. PMID- 2256168 TI - Effect of oxidized and reduced glutathione in liver preservation. AB - Glutathione spontaneously oxidizes in the UW solution for organ preservation and reduced glutathione (GSH) is converted to oxidized (GSSG) glutathione. To determine the effects of the oxidized or reduced forms of glutathione on liver preservation dog livers were preserved for 24 and 48 hr with the UW solution containing either GSH or GSSG. After 24 hr of preservation the form of glutathione did not affect survival or the postoperative course of the animals. All animals survived (three per group) with near-normal liver functions by the third to fifth postoperative day. When preservation was extended to 48 hr survival was 100% (6/6) with GSH and 29% (2/7) with GSSG. The dogs that died developed primary nonfunction of the liver. This study shows that GSH is an important component of the UW solution for 48-hr preservation of the dog liver. The presence of GSSG does not prevent successful 24-hr preservation of the liver, which has been confirmed in clinical studies. However, for 48-hr preservation GSH is required and GSSG is not suitable. PMID- 2256169 TI - The influence of prophylactic immunosuppressive regimens on natural killer and lymphokine-activated killer cells in renal transplant recipients. AB - We investigated natural-killer cells in 81 renal transplant recipients (RTR) in order to define what kind of in vivo prophylactic immunosuppression could be responsible of the impairment of these NK cells. Cell-surface phenotyping was performed by direct immunofluorescence with Leu7 (CD57), Leu11 (CD16), and Leu19 (CD56) antibodies, in one- and two-color stainings. Functional properties were analyzed with freshly isolated nonadherent mononuclear cells (NK activity) and after in vitro activation with r-IL-2 (LAK activity), in cytotoxicity assays using K562 and Daudi tumor lines as specific targets. A flow cytometry technique using carboxy-Fluorodiacetate was applied to monitor the cytotoxicity of NK cells. Our data emphasize the already known deficiency of NK cells: both NK subsets (CD16+ and/or CD56+) and NK activity were decreased in RTR. Moreover, we demonstrated that the in vitro IL-2-induced LAK cytotoxicity was also diminished in RTR. NK cells and functions were normal in RTR treated with cyclosporine only, decreased in RTR treated with both cyclosporine and azathioprine, and at the lowest level in RTR treated with azathioprine without cyclosporine. A multivariate statistical analysis found a negative linear regression between the doses of azathioprine and the number of functions of NK cells, confirming that azathioprine was responsible for the deficiency of NK cells in our RTR. PMID- 2256170 TI - The use of duplex Doppler ultrasonography to evaluate renal allograft dysfunction. AB - This study evaluated the utility of duplex Doppler sonograms (DS) and the resistive index (RI) in the identification and differential diagnosis of various causes of renal allograft dysfunction. The efficacy of DS and RI was studied either during acute episodes of allograft dysfunction or during periodic posttransplantation longitudinal analyses. The unique features of each renal allograft results in poor correlative value for single isolated measurements of RI. We observed that the highest RIs were in ATN and that an RI of 0.9 was not specific for acute vascular rejection. Also, an RI of 0.9 was rare in acute cellular rejection. RI could not distinguish acute rejection, chronic rejection, CsA toxicity, or obstruction, although the mean RI was significantly different from normal in these groups. Serial studies of RI did document a change at the time of a clinical event compared to baseline. It is concluded that RI is not specific to any one clinical entity. PMID- 2256171 TI - The use of cadaver kidneys for transplantation in young children. AB - The role of cadaver kidney transplantation in the management of end-stage renal disease in young children is controversial. To assess the current risk-benefit ratio of cadaver first and second kidney transplants in recipients under 6 years of age, we compared the outcome of 19 transplants performed between 1984 and 1989 using a quadruple-drug regimen (Minnesota antilymphocyte globulin, azathioprine, prednisone, cyclosporine) with the outcome of 25 transplants performed prior to 1984 without the use of cyclosporine at a single institution. Twenty-five transplants were in children under the age of 3 years. In the last decade patient survival has significantly improved. One-year patient survival improved from 53% before 1979 to 90% since 1979 (P less than 0.05). The use of the quadruple-drug regimen since 1984 was associated with a significant improvement in one-year cadaver graft function from 40% before 1979 to 78% in recipients under 6 years of age, and from 22% to 82% in recipients under 3 years of age (P less than 0.05). With the quadruple-drug regimen, one-year and four-year graft function rates for children under 6 years of age were 83% for first cadaver transplants and 72% for second cadaver transplants, which were essentially the same results as in older children and adults. Children who received kidneys from donors over 4 years of age achieved the best result, with 87% one-year graft function compared with 50% for kidneys from donors under 4 years old. In 15 children with successful transplants, 8 (53%) showed accelerated growth, 5 (33%) had normal-velocity growth, and only 2 children (14%) with suboptimal renal function had poor growth following transplantation. Therefore, we believe that with a quadruple-drug immunosuppressive protocol, cadaver renal transplantation using kidneys from adults or pediatric donors over 4 years old is an acceptable form of treatment in young children with end-stage renal disease for whom there are no suitable living related donors. PMID- 2256172 TI - The value of repeated renal retransplantations. AB - The outcome of 64 repeated renal retransplantations (50 third, 13 fourth, and 1 fifth) during a period of 25 years was retrospectively evaluated. The prognosis of third and subsequent grafting was greatly improved if cyclosporine was included in the induction immunosuppressive regimen (one-year graft survival 79.9%, compared with 32.4% if CsA was not used). The onset of graft function was not delayed by CsA and the proportion of never functioning grafts was significantly lower (5.3%) in patients treated with CsA than in those treated without it (43.2%). Survival of the previous grafts for longer than one year favorably influenced the outcome of the subsequent grafts. PMID- 2256174 TI - Lifesaving connections--communications, coordination, and transplantation. AB - Thousands of people suffer and die, and numerous biomedical experiments are cancelled or scaled back each year because of an unnecessary shortage of organs and tissues for transplantation and research. Exacerbating the shortage is the absence of effective national coordination of organ and tissue procurement and the lack of systematic attention given to educating the public and the medical profession about transplantation and donation. The National Organ Transplant Act, passed by Congress in 1984, was an incomplete, narrowly focused, and inadequately funded effort to address these issues. We recommend the more effective use of advanced communications technologies and skills to assure a unified, concerted effort to bring the benefits of donated organs and tissues to greater numbers of Americans. We must ensure that advances in computers, telecommunications, mass media, and interpersonal communications are employed to ensure the coordination of procurement agencies with each other and with physicians and biomedical researchers, the systematic education of physicians and families, and the increased involvement of the public. Realization of the full potential of transplantation will not be possible without a renewed spirit of cooperation, better funding, and sustained political support from both the public and policymakers. PMID- 2256173 TI - The prevalence of hyperlipidemia in renal transplant recipients. Associations with immunosuppressive and antihypertensive therapy. AB - To determine the extent of persisting hyperlipidemia in renal transplant recipients receiving modern maintenance immunosuppressive and antihypertensive therapy we compared plasma levels of total and high-density lipoprotein and triglyceride in 275 renal transplant recipients with stable graft function with age- and sex-matched groups from the local general population (n = 4055). Total cholesterol and triglyceride were higher in transplanted patients in all age groups, but the difference was much more striking in women. Plasma levels of HDL cholesterol were similar or slightly lower in transplanted patients. Association with parameters of graft function, immunosuppressive therapy, and antihypertensive therapy were studied within the transplanted population using multiple regression. Total cholesterol was significantly and independently associated with age, sex, diuretic therapy, and urinary protein. In 127/134 (95%) of patients the diuretic was a loop diuretic. None of the other classes of antihypertensive drug was independently associated with serum cholesterol. The only variables significantly associated with HDL cholesterol were sex and the plasma creatinine. Plasma triglyceride was significantly and independently associated with both diuretic therapy and beta-blocker therapy and with age, urinary protein excretion, and plasma albumin. Plasma cholesterol, HDL cholesterol, and triglyceride levels were almost identical in patients receiving triple therapy (cyclosporine 3-5 mg/kg; prednisolone 7-10 mg o.d.; azathioprine 1 1.5 mg/kg) to those in patients receiving conventional immunosuppression (prednisolone 7-10 mg o.d.; azathioprine 2-2.5 mg/kg). Thus these results do not support the existence of a persisting long-term effect of cyclosporine on plasma cholesterol and triglyceride at these doses of the drug. The more striking abnormality of plasma cholesterol and triglyceride in females is unexplained but might be connected with greater sensitivity to low doses of corticosteroids. PMID- 2256175 TI - Study of epigenesis throws up new targets for drug research. PMID- 2256176 TI - Abnormalities in neural control of smooth muscle in virus-infected airways. PMID- 2256177 TI - Reverse pharmacology applied to the cannabinoid receptor. PMID- 2256178 TI - Magnetic resonance as a non-invasive tool to study metabolism in pharmacological research. PMID- 2256179 TI - This and that: drug tolerance and great expectations. PMID- 2256180 TI - Cumulative frequency curves in population analysis. PMID- 2256181 TI - Dopamine D1 receptor antagonism in schizophrenia: is there reduced risk of extrapyramidal side-effects? AB - The first selective D1 dopamine receptor antagonist, SCH23390, has been reported to be active in preclinical tests that predict antipsychotic activity in schizophrenic patients. This is particularly exciting because it has been claimed that this compound is 'atypical', in that it has a reduced propensity to induce extrapyramidal side-effects. However, in considering the evidence from preclinical screening tests for antipsychotic activity and extrapyramidal side effects of potential neuroleptic drugs, Jarmo Hietala and colleagues conclude that the majority of available data is not compatible with the postulated atypical profile of SCH23390. PMID- 2256182 TI - Clinical significance of pharmacological modulation of homocysteine metabolism. AB - The metabolic fate of homocysteine is linked to vitamin B12, reduced folates, vitamin B6 and sulfur amino acids. Clinical and experimental data suggest that elevated plasma homocysteine is an independent risk factor for premature vascular disease. This is particularly significant because plasma homocysteine levels are altered in several diseases, including folate and vitamin B12 deficiencies, and because many commonly used drugs have now been shown to interfere with homocysteine metabolism. In summarizing the data, Helga Refsum and Per Ueland highlight the clinical implications for these metabolic changes. PMID- 2256183 TI - Structure-activity relationships of K+ channel openers. AB - Seven groups of synthetic agent, distinguished by a combination of their chemical and pharmacological characteristics exert some or all of their effects by opening plasmalemmal K+ channels primarily in smooth muscle. Progress over the past two years now allows broad structure-activity relationships to be formulated within many of the individual groups of agent. Gillian Edwards and Arthur Weston review the historical basis of these discoveries and comment on the significance of new developments. They focus on the search for tissue and channel selectivity, two factors likely to be important for the successful clinical deployment of these substances as antihypertensive and bronchodilator agents. PMID- 2256184 TI - Parental occupation and other environmental factors in the etiology of leukemias and non-Hodgkin's lymphomas in childhood: a case-control study. AB - We report the results of a hospital-based, case-control study on acute lymphocytic leukemia (ALL), acute non-lymphocytic leukemia (AnLL) and non-Hodgkin lymphoma (NHL) in childhood. The study was conducted from 1981 to 1984 in Turin (Italy). One hundred and forty-two children with ALL, 22 with AnLL and 19 with NHL were included, as well as 307 controls. Information on parental smoking habits, parental occupation, ionizing radiation and childhood diseases were collected using a standard questionnaire during a personal interview of the relative attending the child in the hospital. The odds ratios for antenatal diagnostic radiation were 1.1 (NS) for ALL and 2.4 (NS) for AnLL. No association was found with diseases in childhood. Paternal and maternal smoking habits were similar for ALL cases and controls. Both maternal and paternal smoking were associated with NHL: for paternal smoking, odds ratios were around 5, but without a correlation with number of cigarettes. Positive associations observed with maternal employment were: ALL with teacher and cleaner; AnLL and textile worker; NHL and baker. Corresponding association with paternal jobs were: ALL with clerks, farmers and employment in office equipment production; AnLL and workers in building, tire or textile industries; NHL and lorry drivers, workers in the building or in the wood and furniture industry. PMID- 2256185 TI - Projections to the end of the century of mortality from major cancer sites in Italy. AB - We used an age-period-cohort model with arbitrary constraints on the parameters, fitted to the mortality data for the period 1955-84, to project rates in mortality from all cancers and 11 major cancer sites in Italy for the period 1985 1999. For all neoplasms considered, using estimated age and cohort values, two models were fitted, one based on constant period effects, and one on a linear regression on the logarithm of the six calendar periods. Furthermore, "a priori" defined coefficients based on epidemiologic inferences were given to period values for tobacco-related neoplasms (below unity for males, above unity for females, on the basis of recent trends in tobacco prevalence in the two sexes), for breast and ovarian cancer (in relation to the potentially different effect of oral contraceptives, other female hormones, reproductive factors and treatment on these neoplasms), and for total cancer mortality. This produced a range of potential estimates, which were reasonably similar for neoplasms (such as stomach, intestines, breast, ovary or prostate) for which no major change in slope of the cohort effects was evident, but wider (i.e., between 188 and 264/100,000 males aged 40 to 79 in 1995-99) for lung or other tobacco-related cancers. Although this range of variation is far from negligible, the estimated values indicate that lung cancer among Italian males aged 40 to 79, even under the more optimistic assumption, will probably be higher at the end of the century than in the early 1980's, and that lung cancer alone will account for 35 to 42% of all cancer deaths in males between 40 and 79 years. Though any prediction has, by definition, inherent difficulties and uncertainties, cancer mortality in the near future will be strongly influenced by age and cohort effects already known, and hence its projections may offer some indication of public health relevance. PMID- 2256186 TI - Clinical characteristics, diagnosis and treatment of elderly patients with lung cancer at non-surgical institutions: a multicenter study. North-Eastern Italian Oncology Group. Neoplasms of the Elderly Committee. AB - A multicenter retrospective study was undertaken in northern Italy to assess clinical characteristics and pattern of care of elderly patients (greater than 70 years) with lung cancer seen in 1984, at 14 non-surgical institutions. Overall, 1 out of 5 patients with lung cancer was elderly. Eighty-four percent of the 264 elderly patients under study were males, and overall, their median age was 76 years. Squamous cell carcinoma was the most frequent histologic type (53%), and most of the patients (61%), after a rather intensive diagnostic workup, had loco regional disease. Sixty-three percent of patients underwent radiotherapy, which was mostly classified as palliative. Chemotherapy was given to 13% of patients, mostly with small cell histology. Response to radiotherapy and chemotherapy was observed in about 50% of the patients; however, 3 out of 34 (10%) patients treated with chemotherapy died from toxicity. The median survival time from diagnosis was 9.9 months; survival time was not related, in this population of elderly patients, to age. Throughout the study, the quality of data recording during the patient's illness was often found to be suboptimal. In conclusion, elderly patients with lung cancer appear to be actively staged and treated outside a protocol context in the clinical practice of cooperating nonsurgical institutions in northern Italy. This stresses the importance of prospective studies aimed to evaluate the cost/effectiveness of the various procedures used and the impact of treatments used (or even of a policy of no treatment) on the survival and quality of life of these patients. PMID- 2256187 TI - Survey of performance of cervical cytopathology laboratories and of screening programs in Italy. National Working Group for Quality Assurance in Cytohistopathology. AB - Structure, performance, management, quality control and participation in screening programs of cervical cytology laboratories have been evaluated through a questionnaire sent to all public Italian hospitals, relevant university departments and senior members of relevant scientific associations. Completed questionnaires were received from 276 centers, which gives a response rate of 73%. In this report we concentrate on the need for improvement, but there are a number of centers who have all or almost all the features traditionally associated with good or excellent practice. The main results of the survey are the following. Most of the centers examine relatively few cervical smears, so their workload could be considered too low for maintaining a good level of practice. Six centers examine 3 specimens per woman, about 25% examine 2 specimens, and the rest only 1 specimen. There is a marked variability in filing and storing practices of positive and negative smears and results. Internal quality control is inadequate in most centers, and external quality control is limited to voluntary exchange of dubious or interesting smears. Only half of the centers are involved in screening programs. In 75% of the programs the suggested screening interval is 1 year or even 6 months; only 7 (4.5%) agree with the UICC/IARC recommended interval of 3 years. The target population coverage varies from 10% to 85%, and it is less than 50% in 78% of the programs. Only 6 programs have an active women's call system. The survey has confirmed the need for launching a national program of internal and external quality control. Almost all centers have expressed their interest to take part. PMID- 2256188 TI - The influence of female hormones on malignant melanoma. AB - Several lines of biological evidence have suggested a relationship between the behaviour of melanocytes and cutaneous malignant melanoma (CMM) and the action of female hormones. The present overview, however, indicates that the effect of reproductive, menstrual and hormonal factors, including oral contraceptives, on onset and outcome of CMM must be very weak, if any. The only consistent findings which may suggest a role of female hormones on CMM seem to be: 1) a different distribution by anatomic site in men and women, and 2) a more favorable outcome of CMM in women as compared to men. Neither of them, however, necessarily implies a direct effect of female hormones on CMM. PMID- 2256189 TI - Enhancement of adriamycin cytotoxicity in sensitive and resistant sublines of human tumor cells by calcium antagonists. AB - The effect of the calcium antagonists cepharanthine and verapamil on adriamycin induced cytotoxicity against sensitive (K 562 and Ov 2780) and resistant (K 562/ADM and AD 10) sublines of human tumor cells was evaluated. Nontoxic concentrations of cepharanthine moderately enhanced adriamycin cytotoxicity against sensitive sublines (2.1-2.5 fold). A significant enhancement (13-26 fold) of drug cytotoxicity was observed when resistant cells were treated with a combination of cepharanthine and adriamycin. The calcium influx blocker verapamil (used for comparison) also enhanced adriamycin cytotoxicity, although to a lesser extent. The fact that enhancement was 6-10 fold greater in resistant then in sensitive cells, as well as the loss of biphasic properties of adriamycin on dose response curves after combined treatment, indicate that cepharanthine may play a role in overcoming drug resistance in some tumor cells. PMID- 2256190 TI - Transfection of human breast epithelial cells with foreign DNA using different transfecting techniques. AB - The introduction of DNA into eukaryotic cells is a powerful technique for the study of gene regulation. This requires both a technique by which genes can efficiently be introduced into cells and a recipient cell representative of the tissue under study. We have utilized a spontaneously immortalized human breast epithelial cell line, CMF-10, which is phenotypically normal for introducing a neomycin-resistant gene contained in the plasmid Homer 6 (pHo6). Three different transfection methods were tested: calcium phosphate, with and without glycerol shock, using as control NIH/3T3 cells, and strontium phosphate and electroporation. In MCF-10 cells the efficiency of calcium phosphate mediated DNA transfection, which was measured as the number of colonies growing in neomycin containing medium, was 21 and 140 fold higher than in MCF-10 cells transfected by electroporation and strontium phosphate methods, respectively. Glycerol shock enhanced three fold transfection efficiencies. NIH/3T3 transfected cells by calcium phosphate method showed a transfection efficiency similar to that of MCF 10 cells, however, glycerol shock did not improve the efficiency. These studies revealed that calcium phosphate combined with glycerol shock is the most efficient technique for transfection of genomic DNA into human breast epithelial cells. PMID- 2256191 TI - A phase II study of idarubicin and prednisone in multiple myeloma. AB - Twenty-one patients with multiple myeloma were treated with idarubicin 45 mg/m2 orally day 1 and prednisone 60 mg/m2 day 1-4 every three weeks. Moderate to severe gastrointestinal and hematopoietic toxicity were observed. Twelve of the twenty-one patients had relapsed on prior treatment. Of these, 2 patients responded. Two patients had primary resistant disease, neither responded. Seven patients had received no prior treatment, three responded. Idarubicin and prednisone have modest activity in refractory myeloma, with short duration of response and severe toxicity. PMID- 2256192 TI - High-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma. AB - A chemotherapy regimen with epirubicin (60 mg/m2, days 1, 2 and 3) and cisplatin (30 mg/m2, days 2, 3, 4 and 5) was started for 35 patients with advanced soft tissue sarcoma (28 males and 7 females; median age, 50 years). All patients were chemotherapy-naive and with an expected survival of more than 2 months. All patients were evaluable for activity and toxicity. The intercycle interval was 4 weeks. Median number of cycles applied was 4 (range, 2-8). The overall response rate was 20/35 (57.1%). A complete response (CR) was achieved in 7/35 patients (20%), lasting for 26+, 26+, 13+, 13+, 9+, 9+ and 5 months; 13/35 patients (37.1%) entered a partial remission (PR), 9/35 patients (25.7%) had stable disease (SD), and 6/35 (17.1%) had progressive disease (PD). In non-responders (SD + PD), the median survival was 4 months; the median survival of responders (CR + PR) was 9+ months (the median has not yet been reached). Hematologic toxicity of grade 4 was present at least in one cycle for hemoglobin in 6/35 patients, for leukocytes in 22/35, and for platelets in 13/35. No hemorrhagic syndrome was observed. The leukopenia was usually of short duration (nadir on days 10-12). Febrile episodes were present in 18 patients during the nadir of leukopenia. No other significant toxicity was noted (apart from grade III alopecia in all patients), and specifically, there was neither acute nor cumulative cardiotoxicity. PMID- 2256194 TI - Diagnostic efficacy of physical examination, mammography, fine needle aspiration cytology (triple-test) in solid breast lumps: an analysis of 1708 consecutive cases. AB - The clinical-radiologic-cytologic triplet was used for diagnostic evaluation in 1708 women over 30 years old with a breast lump. All the lumps were subjected to surgery except for 258 cases in which clinical resolution took place within 1-2 months. Seven-hundred and ninety-three out of 1450 nodules removed were cancers. Sensitivity of the clinical, mammographic and cytologic examinations was 82%, 73% and 68%, respectively. It increased to 95% when they were associated. Specificity was 63%, 80% and 97%, respectively. The predictive value of positive results of the triple test was 100%. No patient with malignant cytology was subsequently shown to have benign disease. The systematic use of the triple test in solid breast lumps for the early detection of cancer is recommended as a routine procedure. However, participation of experienced radiologists and pathologists as well as physicians skilled in fine needle puncture is required. PMID- 2256193 TI - cis-platinum-based alternating non-cross-resistant chemotherapy as a first-line treatment in metastatic breast cancer. A phase II study. AB - Exposure to multiple non-cross-resistant drugs should increase cell kill and the chance of achieving more complete and partial responses. Our earlier study in breast cancer showed that second-line CAP (cyclophosphamide, adriamycin, cis platinum) treatment was not cross-resistant to the CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) regimen and produced a 51% response rate. These facts initiated a phase II study which used an alternating CMFVP/CAP regimen. Altogether, 49 patients entered the study and 45 were evaluated (greater than 2 cycles). The CMFVP regimen consisted of cyclophosphamide (200 mg/m2 on days 1, 2, 3, 4 and 5), methotrexate (30 mg/m2 on days 2 and 4), 5-fluorouracil (500 mg/m2 on days 1, 3 and 5), vincristine (1.4 mg/m2 on days 1 and 5), and prednisolone (40 mg p.o. on days 1-5), and was alternated with the CAP schedule (300 mg/m2 cyclophosphamide on days 1, 3 and 5, 50 mg/m2 adriamycin on day 1, and 30 mg/m2 cis-platinum on days 1, 3 and 5). Overall response was high, and 37 patients out of 45 responded (82%), with a 28% CR rate (13/45). A particularly high response rate was observed in soft tissues (86%, 18/21) and visceral organs (84%, 16/19). Only 1 patient progressed (3%). The duration of remission was 4-21+ months (median, 12 months). Six of 13 CR patients were still disease free 15 months after the treatment was stopped. The duration of survival was 5-25+ months (median, 15+ months). Toxicity was moderate (myelosuppression in 53% of patients, mainly grade I-II; stomatitis in 11%, except for 100% alopecia and 90% nausea and vomiting). One drug-related death (bone marrow aplasia) was recorded. The high antitumorigenic activity of the alternating regimen used is encouraging and may call for a randomized study for the ultimate evaluation of this treatment approach. PMID- 2256195 TI - Chemotherapy in metastatic nonanaplastic thyroid cancer: experience at the Institut Gustave-Roussy. AB - Forty-nine patients with metastatic nonanaplastic thyroid carcinoma were treated over a 10-year period. Five successive chemotherapeutic protocols were used: a combination of doxorubicin, etoposide, 5-fluorouracil and cyclophosphamide; elliptinium acetate; doxorubicin; cisplatin; and the combination of doxorubicin and cisplatin. Results obtained with the different protocols were very disappointing, with only two objective responses (3%). Phase II trials with new chemotherapeutic agents are warranted in selected cases of nonanaplastic metastatic thyroid carcinoma. PMID- 2256196 TI - Therapeutic possibilities of 131I-MIBG in metastatic carcinoid tumors- preliminary report. AB - The poor results of traditional therapy in advanced carcinoid tumors and the well proven uptake of 131I-MIBG shown by some of these tumors induced us to attempt a radiometabolic approach. We selected for the treatment 5 patients (3 men and 2 women) who showed progression of disease, a fairly good uptake of 131I-MIBG with severe related symptoms, and a poor response to traditional therapy. A cumulative radioactivity of 5.5-29.6 GBq was given. Acute side effects after 131I-MIBG administration or late radiation-induced damages were not observed. Symptoms increased during the first 2-4 weeks in 2 patients: in one of these relief was achieved with drugs. Results concerning objective remission of the disease were unsatisfactory. In contrast, definite improvement of symptoms was shown in 2 of 5 patients, resulting in a better quality of life. PMID- 2256197 TI - Ultrasonographic evaluation of palpable breast masses: analysis of 134 cases. AB - Sonography has become a helpful adjunct to mammography mainly for a differential diagnosis between simple cysts and solid masses. The authors examined by ultrasound 134 palpable masses in the breast which had been previously evaluated by clinical examination and mammography and then submitted to biopsy or fine needle aspiration. The exact diagnosis of a simple cyst was made in 94.1% of the cases, whereas the diagnosis of fibroadenoma was made in 80% of the cases. Ultrasound examination proved to be useful in patients with dense breasts: in this group, 82.1% of the patients with a histologic diagnosis of benign status had a correct ultrasound diagnosis. In agreement with other authors, we believe that breast sonography has no part in screening programs. PMID- 2256198 TI - Diagnosis of malignant change in duodenal villous adenoma. AB - Villous adenomas of the duodenum are rare, and malignancy is discovered in about 30% of the lesions. The authors describe two cases of villous adenoma of the second portion of the duodenum (13 and 8 cm in diameter). The diagnosis was obtained through endoscopy, which did not demonstrate any malignant change. In both patients, malignant change was shown by intraoperative frozen sections, and a pancreatico-duodenectomy was performed. Review of the literature and the authors' experience indicate endoscopic biopsies do not rule out the presence of malignancy in adenomatous pathology of the duodenum. Therefore, laparotomy should be performed whenever endoscopic excision of the neoplasm is not feasible. The authors emphasize the importance of an intraoperative diagnosis based on accurate frozen sections and propose a correct procedure to obtain the best results. PMID- 2256199 TI - Phase II study with high doses of epirubicin in patients with advanced rectal cancer. AB - We tested the possible role of epirubicin, 100 to 130 mg/m2 administered i.v. every 3 weeks, in patients with advanced adenocarcinoma of the rectum untreated with chemotherapy. Sixteen of 17 entered cases were evaluable. No complete or partial responses were observed. The median time to progression was 6 weeks, and the median survival was 36 weeks. Reversible leukopenia was the major toxic side effect. The median epirubicin cumulative dose was 330 mg/m2; no patient had clinical cardiac toxicity. With no responses recorded in 16 evaluable patients, the activity of epirubicin in rectal cancer ranged between 0 and 18%, with 95% probability. Further studies with epirubicin in this tumor are not indicated. PMID- 2256201 TI - Uterine benign-appearing smooth muscle tumor "metastatic" to the lungs: a case report. AB - A case of pulmonary fibroleiomyomatosis secondary to a uterine "metastasizing" leiomyoma, with aspects of vascular invasion, is reported. Although we cannot exclude the existence of primitive pulmonary forms, which we do not consider to be of a hamartomatous nature, we believe that a careful examination of the uterus for the presence of angioinvasive leiomyoma is mandatory. PMID- 2256200 TI - Thrombocytopenia following treatment with low doses of aminoglutethimide. AB - The authors report a case of severe thrombocytopenia during treatment with low doses of aminoglutethimide in a woman with advanced breast cancer. Hematologic toxicity secondary to aminoglutethimide did not seem to be dose-related, and an immunologic mechanism may be postulated. Although the incidence of the side effect is probably low, monitoring of blood counts during the first months of therapy is necessary. PMID- 2256202 TI - Inflammatory pseudotumor of the liver: report of two cases. AB - Inflammatory pseudotumor of the liver is a very rare lesion. Herein we describe two cases of this entity which occurred in two women aged 22 and 49 years, respectively. Both cases were considered to be clinically malignant and only the histopathologic examination revealed the non-neoplastic nature of the disease. Ultrastructural and immunohistochemical studies further supported the evidence of a reactive disease. PMID- 2256203 TI - [Fuel for the Danish children]. PMID- 2256204 TI - [Interleukin-2 based immunotherapy of cancer]. AB - Interleukin-2 (IL-2) is produced by activated T-helper lymphocytes and stimulates both the antigen-specific and the non-specific immune defence. In vitro, IL-2 activated peripheral blood lymphocytes (LAK-cells) can lyse a broad spectrum of both NK-sensitive and NK-resistant tumour cell lines and IL-2 expanded tumour infiltrating lymphocytes (TIL) are, in certain cases, selectively able to lyse autologous tumour cells. In vivo, the mechanism behind the anti-tumour effect of IL-2 is unknown. Recombinant IL-2 has been available since 1984 and world-wide more than 3,000 patients have been treated. IL-2 has most frequently been administered in combination with either in vitro activated autologous effector cells and/or other cytokines or anti-cancer chemotherapeutic agents. The generation of autologous effector cells for patient treatment demands considerable resources and their contribution to the clinical effect is uncertain. The best responding tumour-types have been renal cell carcinoma and malignant melanoma with response rates up to 35% and 24%, respectively. IL-2 therapy is associated with considerable side-effects. The most serious are due to the development of a "capillary leak syndrome" with peripheral vasodilation and increased vascular permeability resulting in hypotension, oedema and organ dysfunction. The majority of these side-effects are reversible with improvement within hours after terminating the IL-2 administration. It is concluded that IL-2 therapy is still experimental and it should be limited to treatment according to protocols in highly specialized clinical departments in a close cooperation with immunological laboratories. PMID- 2256205 TI - [Asbestos-induced lung diseases]. AB - Asbestos fibres have potent cancerogenic and fibrogenic properties and may lead to development of cancer and fibrosis in the lung parenchyma and pleura. The Danish Ministry of Employment has established rules which should prevent development of disease when working with asbestos in future but, on account of the very long latent period between exposure and development of asbestos-related disease, these conditions will still occur during the next 30-40 years. Primarily, the more benign pleural plaques will be concerned but serious disease such as bronchial carcinoma and pleural mesothelioma will occur in the future. When patients are encountered who present symptoms or objective/paraclinical findings which are compatible with disease produced by asbestos, it is important to remember that exposure to asbestos may be many decades ago and, particularly where the malignant conditions are concerned, exposure need not have been particularly massive or prolonged. All cases where asbestos-related disease is suspected should be notified to the insurance administration. PMID- 2256206 TI - [Observer variation of the radiographic assessment of pulmonary changes caused by asbestos]. AB - Assessment was undertaken of 165 x-ray photographs of the thorax originating from 165 men with varying degrees of exposure to asbestos: 37 were workers in an eternite factory, 65 insulation workers, 42 were plumbers and 21 were patients from the Lung Clinic in Bispebjerg Hospital. Assessment of the x-rays was carried out according to the directives established by the International Workers' Organisation (ILO) by three experienced specialists who had no knowledge of the individual person's exposure to asbestos or smoking habits. In order to investigate not only inter- but also intra observer variation, the three medical specialists described the material on two occasions with an interval of several days. Analysis of the descriptions revealed that there was considerable inter- and intra-observer variation in assessment of the changes caused by asbestos. Description of the parenchymatous changes was associated with slightly greater variation than description of the pleural changes. A partial analysis of smokers who had not had occupational exposure to asbestos showed a not inconsiderable occurrence (5-33%) of parenchymatous changes which could not be differentiated from changes caused by asbestos. It is concluded, that the diagnosis of pulmonary disease caused by asbestos should not be based on radiographic examination alone. PMID- 2256207 TI - [Food habits and knowledge among Frederiksberg schoolchildren]. AB - In 1989, 674 school pupils in the sixth and eight grades in nine elementary schools replied to a questionnaire with questions about dietary habits and knowledge. More than 70% of the pupils preferred skim-milk products to full milk. Half of the pupils always used butter or margarine on bread. The main reason for using some form of fat on the bread was that, without this, the bread would become too dry. Approximately 75% of the pupils ate brown bread, fresh fruit and vegetables daily. These same pupils had "healthy" dietary habits in many respects. 75% of the pupils avoided one or more types of food because they considered that these were not good for them. The item most frequently avoided was fat meat. 83% of the pupils included some foodstuffs in the diet because they considered that these were good for them. The items most frequently involved were fruit and vegetables. The sex and age differences between the actual diet and the ideal diet were insignificant. More than half of the pupils could state correctly whether 11 different foodstuffs contained much fat, sugar or dietary fiber. No connection was found between the pupils' dietary knowledge and their actual or ideal diets. It is thus probable that dietary advice which emphasizes foodstuffs e.g. eat more dietary fiber, is difficult for them to understand and live up to. More definite dietary information e.g. eat more vegetables, would probably have been easier for the pupils to understand and live up to. School pupils of today are very much aware of the significance of diet for their health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256208 TI - [Smoking and alcohol drinking habits among school children in the Frederiksberg community]. AB - In 1989, a total of 674 pupils in the sixth and eighth grades of nine elementary schools in the Municipality of Frederiksberg replied to a questionnaire which included questions about their habits and attitudes concerning smoking and alcohol. 50% of the girls in the eighth grade smoke, 30% of these daily. Compared with previous investigations, these results support the general impression that the frequency of smoking in girls is increasing. Compared with previous investigations, the frequencies of smoking in boys show a decreasing tendency: 24% of the boys in the eighth grade are smokers and 12% smoke daily. Great agreement was expressed with the negative assertion about smoking and 98% were aware that smoking was dangerous. The commonest reasons given for smoking were that it is a sociable habit, is relaxing and tastes good. Evidence was found that the advantages of smoking should be utilized in anti-smoking campaigns and the disadvantages should be emphasized and that campaigns should be directed to teenage girls. Girls in the eighth grade also drink alcohol more frequently than boys do. 62% of the pupils who had a monthly alcohol intake considered that alcohol was dangerous. A definite connection was found between the consumptions of tobacco and alcohol. No connection was found between active efforts to be healthy and not to smoke or drink. Girls living with a single father employed tobacco and alcohol more frequently. PMID- 2256209 TI - [Substance abuse among school children. A pilot study from Ilulissat/Jakobshavn, Gronland]. AB - A pilot investigation to illustrate the use of euphoriant agents by school pupils in Ilusissat/Jakobshavn in Greenland was carried out. The object was to establish a basic line for this employment and to commence monitoring which has been planned for a preliminary period of five years. In addition, a questionnaire was tested. The investigation was anonymous and the questionnaires were distributed on 14.11.1989. All of the pupils who were present (195 out of 230) participated. The age range was from 13 to 17 years. The investigation revealed a great consumption of tobacco. The alcohol consumption was moderate while hash and sniffing were at city levels (20% and 7%, respectively). Intensive prophylactic measures in the Greenlandic language are required. Similar projects on local bases are important. This investigation will be repeated annually in the same manner and will be extended to several towns in Greenland. PMID- 2256210 TI - [Knowledge about alcohol and alcohol drinking habits in the 7th and 9th grades. A questionnaire study in the county of Roskilde]. AB - A total of 4,044 pupils in the seventh and ninth grades in the County of Roskilde participated in a questionnaire investigation. Approximately 1/10 of the pupils in the seventh grade and approximately 1/3 in the ninth grade drank alcohol once a week or oftener. The majority misapprehension that their peers drank much more often than was indeed the case was striking: in the seventh grade a factor 4 and in the ninth grade a factor 2. In the ninth grade, 0.5% drank alcohol daily and 11.5% a couple of times a week. 3.3% in the ninth grade and 0.5% in the seventh grade took more than ten drinks a week. 34.5% in the ninth grade and 4.9% in the seventh grade drank three or more drinks per week. The number who felt excluded from the community if they did not drink varied from 0 to 20% from school to school. Teaching about alcohol is important. It is, however, also important that, despite stringent economy, efforts are made to capture young peoples interests in a healthy manner in their everyday life. PMID- 2256211 TI - [Tobacco, hashish--knowledge and habits in schools]. AB - A questionnaire investigation was carried out among pupils in the seventh and ninth grades of schools in the County of Roskilde in 1988-1989 to eluciate their knowledge and habits where tobacco and hash were concerned. A total of 4,044 pupils replied to the questionnaire. The investigation was anonymous. 5.7% of the pupils in the seventh grade and 9.7% of the pupils in the ninth grade stated that they smoked daily. At parties, 15.6% of the 13-year-olds and 35% of the 15 year olds smoke. 0.5% of the 13 year-olds and 35% of the 15 year-olds smoke. 0.5% of the 13 year-olds and 44% of the 15 year-olds smoke more than ten cigarettes daily. 2.4% of the pupils in the seventh grade and 12.8% of those in the ninth grade had tried smoking hash. Differences were found between various municipalities and various schools. A total of 1.3% of the 15 year-olds are considered to be regular users of hash. The number of young tobacco smokers is still high and is probably influenced by the attitudes of parents, siblings and peers. Attempts to reduce the numbers of young smokers and to involve the parents in the problem are important. The number of hash smokers is alarming as these adolescents may obtain stronger drugs through the same channels as they obtain hash. It is important that all persons involved in youth welfare should combine their activities in combating these dangers. PMID- 2256212 TI - [Drugs, narcotics--knowledge and habits in schools]. AB - During the school session 1988/1989, the school doctors in the County of Roskilde carried out a questionnaire investigation among 4,004 pupils in the seventh and ninth classes about their knowledge, habits and attitudes to euphorising drugs. The questionnaire investigation was voluntary and anonymous and this probably contributed to the serious replies. Ten municipalities participated and the results showed that more than 50% of the pupils had employed analgesic medicine within the past three months. The consumption of medicine requiring prescription was about 2% during the same period. Medicine was obtained mainly from the parents. Approximately 6% of the pupils in the ninth grade had been offered speed while less than 1% had consumed speed. 1-4% of the pupils had attempted sniffing while only very few had tried cocaine, heroin and morphine. The need for a multidisciplinary health educational campaign concerning euphorising drugs is emphasized. PMID- 2256213 TI - [Recurrent abdominal pain in childhood]. PMID- 2256214 TI - [Screening of HIV in Denmark]. PMID- 2256215 TI - [Classification of research]. PMID- 2256216 TI - [HIV infection and women]. PMID- 2256217 TI - [Informed consent. Historical background and current problems]. AB - At present, informed consent is essential before patients can participate in clinical trials. The fact that a doctor asks the patient for informed consent is an expression of respect for the patient's right to make decisions about his own body. The request is made in recognition of the fact that optimal treatment can only be ensured by means of clinically controlled trials. The need for regulation of research arose at the beginning of the present century when pharmacological development accelerated. The Nurenberg Declaration was elaborated after the second world war and, subsequently, the Helsinki Declarations I and II. In these, directives are established for clinical research and for the rights of participants. A number of conditions make it difficult to fulfill these intentions. It may be difficult to ensure that the patient has adequate basic knowledge. The patient may feel that he is in a state of dependence on the doctor which influences his possibility to choose freely. Confidence between doctor and patient may be undermined if the patient is requested to participate in randomization for choice of treatment. Doctors know too little about how valid information can be ensured. PMID- 2256218 TI - [How can sufficient information be ensured in clinical trials at an oncology department?]. AB - It is difficult to comply with the intention that the patient gives consent to participation in a clinical trial on the basis of complete information. Reasons for this are the doctor's defective knowledge about processes of communication and his desire to protect the patient, and sometimes also himself, from disagreeable information. Solution of these problems requires more knowledge about theories of communication and crises and improved planning in how to provide this information. The patient's possibility of understanding the information on which he can base an independent decision may be improved by offering several conversations, improved presentation of the written information, the presence of a relative at the informative conversation and supplying the patient with a contact person from the staff for further information. It is concluded that more structured informative procedures are necessary in the individual departments in order to ensure that the patient receives sufficient information before giving qualified consent. PMID- 2256219 TI - [Written information in clinical trials at an oncology department]. AB - On the basis of a model for communication, a series of requirements are established for the content and form of written information given in connection with clinical trials. Fourteen texts employed in an oncological department are reviewed. The clarity as expressed by the readability index (lixtal) is found to be considerably less than desired. A series of examples are presented which either make reading difficult or are such that the patient does not receive adequate and relevant information. In particular, information about alternatives to participation in the trial and the possibilities for feedback for the patient are not mentioned. Finally, proposals are made for how the doctor can ensure that the written information is adequate and readable. PMID- 2256220 TI - [Verbal information in clinical trials at an oncology department]. AB - Prior to participation in clinical trials, patients must give their consent on the basis of information from the doctor. The content of the information is defined in the Helsinki Declaration. Information given in an oncological department was investigated and the patients were interviewed about the information obtained. The problems associated with the informative interviews with the patients were that these were frequently unstructured, that the patients were more concerned with their illness and treatment and that doctors had done too little to ensure that the patients had understood the information. It was most difficult for the doctors to provide thorough information about side-effects and disadvantages. Patients had greatest difficulty in understanding the principle of randomization. The patients' main reason for participation in the trial was the hope for therapeutic benefit. In departments where clinical research is undertaken, constant attention is required for how information on clinical trials is best given. PMID- 2256221 TI - [HIV infected women in Copenhagen. Risk factors and sex behavior]. AB - A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test. PMID- 2256222 TI - [Prosthesis-endocarditis in the aortic position in a 22-year case load. Surgical versus conservative treatment]. AB - During the period 1965-1986, a total of 852 patients underwent isolated aortic valve replacement. With 4,875 patients-years at risk, 24 patients developed prosthetic valve endocarditis (PE; 0.49% per patient-year). The five, ten and fifteen year cumulative freedoms from PE were 98.2%, 95.4% and 93.0%, respectively. PE was unrelated to pre- or intraoperative data. No patients submitted to operation for acute/subacute bacterial endocarditis of the native aortic valve developed PE. Out of the 12 episodes of PE within two years of the operation, seven (58%) were caused by Staphylococcus albus compared with two out of 12 (17%; p less than 0.05) subsequent episodes of PE. Seven of the nine infections with Staphylococcus albus were caused by a highly resistant nosocomial variant. Ten of the PE patients underwent replacement of the prosthesis while 14 were treated conservatively. The two therapeutic groups were comparable, although the surgically treated patients tended to be younger and to have more impaired cardiac status. All surgically treated patients and all patients treated conservatively and in whom post mortem verification was possible had paravalvular defects, annular abscesses and/or vegetations on the prosthesis. The thirty-day, one year and ten year cumulative survivals were 80%, 80% and 50%, respectively, after replacement of the prosthesis and 64%, 21% and 7%, respectively, after conservative treatment (p = 0.02). A Cox regression analysis identified conservative treatment, infection with Escherichia coli or Haemophilus influenzae and the need to intensify digitalis/diuretic treatment for congestive heart failure as independent risk factors. It is concluded that replacement of the prosthesis early in the course of the disease should be considered as the treatment of choice. PMID- 2256223 TI - [The use of free maternal preventive services among immigrant pregnant women in Denmark during 1983-1987]. AB - As part of an investigation of immigrants' living conditions in Denmark, we have investigated how pregnant immigrant women utilize the possibility of free examinations during pregnancy. The study is based on data on all deliveries in Denmark in the years 1983-1987, retrieved from the Danish Medical Birth Registry concerning parturient women with permanent address in Denmark and who were born in either one of the Scandinavian countries, Yugoslavia, Turkey, Pakistan, Marocco, Iran of Vietnam. The women born outside Scandinavia gave birth to about 6,500 infants during the study period; roughly half of these were borne by Turkish women. The largest percentage of young parturients were found among women from Turkey and Yugoslavia. Pakistani and Maroccan mothers had higher parity. These two groups were especially concentrated in the municipality of Copenhagen, where half of the parturient women lived. A few lived in the remainder of the country while a total of 85% lived in the metropolitan area. Four out of ten pregnant Turkish or Pakistani women had been examined by a midwife less than the five times recommended. Among those living in the metropolitan area. Danish women have an average total of almost 11 examinations compared to 8.2-8.9 among immigrants. The conclusion of the study is that the immigrant women have less contact with the free antenatal care system during their pregnancies than the Scandinavian women and that the differences are greatest when examinations by the midwife were concerned. Further discussion on antenatal care in Denmark, is required. PMID- 2256224 TI - [Long-term follow-up of patients after a single-freezing treatment of ectocervical intraepithelial neoplasms]. AB - Fifty-five women aged 21-51 years were treated in 1977 and 1978 with cryocoagulation (single-freezing technique) for cervical intraepithelial neoplasia (CIN I-III). 92% of these patients were followed up 7-8 years after this treatment. The primary success rate i.e. the proportion between the number of women in whom dysplastic changes were not re-encountered within the first 15 months after treatment and the total number of women treated was 94.5%. After the period of observation of 7-8 years, the success rate was 100% for CIN I + II and 79.5% for CIN III. PMID- 2256225 TI - [Systemic allergic reaction after ingestion of pine nuts, Pinus pinea]. AB - An in vivo open oral provocation with pine nuts (Pinus pinea) confirmed information about systemic reaction after ingestion of pine nuts. In vitro tests suggested a systemic IgE allergic reaction. Pine nuts are employed in sweets and cakes and, as in the present case, in green salads. PMID- 2256226 TI - [Postoperative synergistic infection]. AB - Two cases of synergist postoperative infection are described. The importance of radical wound toilet and broad-spectrum antibiotic treatment is emphasized. Synergist infection should be borne in mind in cases where postoperative wound infection continues to spread despite thorough wound toilet. PMID- 2256228 TI - A ray tracing approach to restoration and resolution enhancement in experimental ultrasound tomography. AB - Recursive ray tracing is applied for experimental time-of-flight projection data to achieve a resolution enhancement over the initial straight-ray reconstructed velocity image. Curved-ray reconstruction is performed using the dedicated simultaneous algebraic reconstruction technique (SART). Tomographic reconstructions from experimental data are compared to images obtained from simulated projection data for a refractive field mimicking the actual tissue equivalent phantom. The simulation study adequately explains the macrostructural geometric distortion and loss of resolution in the straight-ray image due to refraction effects that are unaccounted for. PMID- 2256227 TI - Statistics of the physiologic phase of integrated backscatter from canine myocardium with normal and reduced coronary circulation. AB - The phase, relative to the arterial pressure, of cyclically varying integrated backscatter from canine myocardium was measured at normal and reduced coronary blood flow levels and was found to become more randomized with decreasing flow. The phase, modeled as a von Mises distribution on a unit circle which is very similar to the normal distribution on the line, is characterized by a mean (mu 0) and a concentration or width parameter (kappa). kappa is used to characterize the degree of randomization. The von Mises distribution provides an excellent fit to measured data (p less than 0.01). Hypothesis tests performed on the data for various coronary flow levels indicate that the phase distribution for normal coronary flow level is significantly different from the distributions at other flow levels (p less than 0.05). The results suggest that the parameter kappa may be used for differentiating normal and ischemic myocardium. PMID- 2256229 TI - Phase detection in acoustic microscopy. AB - The scanning laser acoustic microscope provides a relatively simple means by which speed of sound data can be collected from biological specimens. By employing a phase detection circuit, phase-contour lines can be superimposed on acoustic micrographs and digitized for direct speed of sound calculations. Because of the existence of mild field non-uniformities, the phase reference must be mathematically modeled. This is accomplished by employing a polynomial function and simple linear regression. Scattering can be studied by using a frequency-selective "dark field" approach. Speed of sound maps are readily produced from the phase data by applying the simple geometric relationships of wave propagation; however the theoretical limitations of the technique must be kept in mind. Using this approach, useful data have been obtained. PMID- 2256230 TI - Transducer characterization from pressure amplitude distribution measurements using a Kalman filter as parameter estimation algorithm. AB - The amplitude and frequency contents of a received ultrasound pulse depends on the spatial pressure amplitude distribution of the sound field, as produced by the transducer in the medium, and on the position and orientation of the reflecting surface in this field. Often, the geometry of the reflecting surface and the acoustical properties of the medium are known or can be estimated. Then it is practical to determine the transducer parameters in order to calculate the distortion of a reflected ultrasound pulse. Apart from geometrical parameters such as size and mechanical focusing, the surface velocity amplitude distribution (SVAD) of a transducer is of major importance. For some transducer configurations this SVAD may be described with a limited number of parameters. This paper presents a method, based on a Kalman filter algorithm, to assess the transducer parameters by measurement of the spatial sound field pressure amplitude distribution in various planes for different emission frequencies. Comparison of the measured pressure amplitudes with those calculated using the estimated values of the parameters shows that this method yields reliable results. PMID- 2256231 TI - Influence of differences in tumor vascularity upon the effects of hyperthermia. AB - Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5 degrees C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors. PMID- 2256232 TI - Development of N-butyl-N-(hydroxybutyl)-nitrosamine-induced tumors in the partially resected, proliferating rat urinary bladder in dependence upon the time of onset of stimulated DNA synthesis. AB - Tumor development was investigated in the partially resected, proliferating urinary bladder of rats in dependence upon the onset of stimulated de novo DNA synthesis related to carcinogen dosing. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) was used as carcinogen and administered by gavage in three fractionated doses (100 mg/kg body weight each) either during the phase of the most pronounced proliferation of the urothelium 30, 45 and 70 h after one-third resection of the bladder or 24 h and 1 week prior to partial cystectomy. When BBN was given during most increased DNA synthesis subsequent to one-third resection, the incidence of bladder tumors was reduced to 8.7% compared with 19.6% found in control animals with a non-resected, quiescent bladder. Tumor formation was neither inhibited nor enhanced when BBN was initially administered, followed by partial cystectomy 24 h or 1 week after the last carcinogen dose, yielding tumor incidences of 18.2% and 22.5%, respectively. Thus, the feeding of BBN during the period of maximum DNA synthesis inhibited tumor development in the partially resected bladder, while stimulation of cell replication subsequent to carcinogen administration did not influence the carcinogenic process initiated. The results obtained indicate that time of onset of stimulated DNA synthesis related to carcinogen dosing is the decisive factor in modifying urothelial carcinogenesis in the proliferating urinary bladder. PMID- 2256233 TI - Rat urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and N-methyl-N-nitrosourea. AB - The present investigation was conducted to examine the combination effect of N butyl-N-(4-hydroxy-butyl)nitrosamine(BBN) and N-methyl-N-nitrosourea(MNU) in rat urinary bladder carcinogenesis. Experiment 1 was performed in the groups treated by oral BBN administration in combination with MNU intravesical instillation and their control groups. In the groups given both BBN and MNU, the ratio of rats with the nonpapillary type to carcinoma-bearing rats was significantly higher than in the controls. Since most of the carcinomas were non-invasive, the observation period was prolonged in the groups given both BBN and MNU in experiment 2. However, even after a longer observation period, no invasive carcinoma was observed. These results suggest that high-grade and invasive carcinomas similar to those induced by BBN and MNU in the heterotopically transplanted rat bladder cannot be induced in the natural bladder of the rat. PMID- 2256234 TI - The proportions of fiber types in human external urethral sphincter: electrophoretic analysis of myosin. AB - The proportions of fast and slow myosin molecules in external urethral sphincter specimens from ten urodynamically normal male bladder carcinoma patients were estimated from the contents of fast and slow myosin light chains in two dimensional electrophoretic gels. The percentages of fast and slow myosin molecules ranged from 5.0% to 61.4% with a mean of 35.5% and from 38.6% to 95.0% with a mean of 65.5% respectively. It is therefore concluded that the human external urethral sphincter is composed of both fast and slow muscle fibers as well as other voluntary muscles. The human external urethral sphincter is considered to be a highly fatigue-resistant muscle with a very high proportion of slow muscle fibers. In the cases studied so far, there is a great diversity in the proportions of fast and slow myosin molecules; the reason for this remains unknown. PMID- 2256235 TI - Effect of distension on adrenergic innervation of the rat urinary bladder. AB - The effect of distension on adrenergic innervation was investigated in the rat urinary bladder. Bladders were distended for 3 h by forced diuresis and balloon obstruction, and specimens were taken from the bladder dome, body and neck for the demonstration of glyoxylic acid-induced fluorescence of catecholamines. Depletion of catecholamines started after 10 h and was almost complete after 2 days. The fluorescence had recovered part way after 5-7 days and was practically normal after 21 days. Small, intensely fluorescent (SIF) cells in the ganglia continued to leak catecholamines throughout the 21-day study period. The primary clinical success of distension therapy for the treatment of unstable bladder may be at least partly due to a reversible disturbance in the function of the adrenergic nerves, which have an excitatory alpha-adrenergic dominance in such cases, but the persistent leakage from SIF cells raises the question of whether distension causes prolonged disturbances in bladder function. PMID- 2256236 TI - Comparison of the mode of action of prostaglandin E2 (PGE2) and sulprostone, a PGE2-derivative, on the lower urinary tract in healthy women. A urodynamic study. AB - The influence of intravesical administration of PGE2 (1,500 micrograms) and sulprostone, a PGE2 derivative (1,000 micrograms) on urodynamic parameters of the lower urinary tract was tested on six healthy female patients. PGE2 and sulprostone significantly decreased the urethral closure pressure at rest. PGE2 increased the detrusor opening pressure as well as the detrusor pressure during maximum flow. Sulprostone, in contrast, slightly decreased these parameters. Both substances caused a strong urgency sensation resulting in an equally reduced bladder capacity and leading to a measurable bladder instability in both cases. This gives rise to the assumption that frequency, urgency and bladder instability may be the result of intravesical relaxation. By 24 h after administration all urodynamic parameters had returned to pretreatment values, thus indicating that long-term changes in urodynamic parameters are not found after either prostaglandin. PMID- 2256237 TI - Construction of a stable nipple valve with processed dermal sheep collagen for continent ileostomy and urostomy. AB - Complications of the nipple valve system used for continent urostomy and ileostomy basically consist of incomplete (or complete lack of) adhesion of the invaginated serosal surfaces of the valve. A novel concept in fixation of the valve by means of the intussusception of a newly developed biomaterial (processed dermal sheep collagen; PDSC) was tested. The implanted PDSC is characterized by induction of fibroblast invasion and formation of new collagen fibers, initial high tensile strength, bio-inertion and (slow) biodegradation. It was implanted between the serosal surfaces of the invagination in 14 dogs without the application of the commonly used staples and synthetic mesh. Good permanent fixation was obtained in all cases after the PDSC had been sutured in place. As the observation time advanced up to 2 years, an increased amount of newly formed collagen was seen anchoring the serosal surfaces firmly together via the implanted PDSC with apparent slow degradation. In none of the test animals did complications occur. The first clinical trial was successful. PMID- 2256238 TI - Encephalopathy found in pig experimental study. PMID- 2256239 TI - An outbreak of anthrax in pigs: a practitioner's account. AB - An outbreak of anthrax occurred in a 500 sow unit at Singret Farm, Llay, during the summer of 1989. This paper describes the sequence of events leading up to the depopulation of the farm, as seen and recorded by a veterinary surgeon in the practice involved. Some of the problems encountered and their significance for the future are discussed. PMID- 2256240 TI - The role of electrical stunning, bleeding and plucking efficiency on the downgrading of chicken carcases. AB - This study examined the effects of inducing a cardiac arrest at electrical stunning, in combination with impaired bleeding and severe plucking, on the incidence of haemorrhages and broken bones in chicken carcases. It was concluded that with the possible exception of breast muscle haemorrhages none of the downgrading conditions were attributable solely to electrical stunning. Poor neck cutting, too severe plucking and flapping of the wings before death also played a part. PMID- 2256241 TI - Intermittent lameness in two cows from detachment of the anterior horn of the medial meniscus. PMID- 2256242 TI - Effects of coat colour on physiological responses to solar radiation in Holsteins. PMID- 2256243 TI - Detection of LT and STIa toxins by latex and EIA tests. PMID- 2256244 TI - Selecting veterinary students. PMID- 2256245 TI - Wellcome Trust's role in veterinary research. PMID- 2256246 TI - Helleborus foetidus poisoning of cattle. PMID- 2256247 TI - Disease in young pheasants. PMID- 2256248 TI - [Pseudoobstruction syndrome of the large intestine (endoscopic therapy)]. AB - The authors present an account on the successful treatment of pseudoobstructive syndrome of the large intestine (Ogilvie syndrome) by decompression, which was achieved by inserting a catheter by means of a coloscope into the transverse colon or caecum. The authors used this method in two patients. PMID- 2256249 TI - [Successful treatment of the superior vena cava syndrome caused by thrombosis and a fibrous septum in a patient with a permanent cardiac pacemaker]. AB - A patient with a ten-year permanent implantation of a pacemaker was admitted on account of a clinically serious syndrome of the vena cava superior. The cause of the syndrome was an angiographically confirmed extensive thrombosis and after its dissolution a fibrous septum in the area of the orifice of the vena cava superior into the right atrium. The septum caused by a fibrous strip at the orifice of the vena cava superior into the right atrium was removed by surgical operation during thoracotomy by dilatation of the original opening in the fibrous septum by a Broca dilator and digitally. The authors recommend, based on their own experience and data in the literature, to use fibrinolytic therapy in clinically severe thrombosis in the area of the vena cava superior or the right atrium caused by an electrode--during temporary or permanent pacing--or by a catheter used for parenteral nutrition. PMID- 2256250 TI - [Evaluation of diastolic left ventricular function using pulsed Doppler echocardiography]. AB - The authors give an account of the evaluation of diastolic functions by means of pulsed Doppler echocardiography. It is a relatively new method which is still seeking its position in the pattern of examinations. However, some authors have already demonstrated that it is valuable and can contribute towards a more accurate description of the functional state of the myocardium and help to detect initial stages of disease. As it is non-invasive, it can be repeated, as required without damaging the patient and thus can be used to follow up the effect of therapy. PMID- 2256251 TI - [Human immunodeficiency virus infection and rheumatology]. AB - The most important rheumatologic manifestations associated with infection with human immunodeficiency virus are described. Among arthritides, Reiter's syndrome, psoriatic arthritis, and some forms of reactive arthritis are the most common. Arthralgias are also relatively frequent. Manifestations of polymyositis, vasculitis and sicca syndrome with a relatively broad spectrum of various autoimmune phenomena are also very important. The author emphasizes the importance of interdisciplinary cooperation of internists, rheumatologists, infectionists and virologists in solving questions associated with laboratory and clinical aspects of the relationship between rheumatologic manifestations and infection with human immunodeficiency virus. PMID- 2256252 TI - [Human immunodeficiency virus infection and the pathogenesis of AIDS]. AB - The prerequisite of effective infection with the virus of human immunodeficiency (HIV) are the interaction between the CD4 complex of the susceptible cell and outer glycoproteins of the virus. The CD4 complex is found above all on the sub population of helper inducer T lymphocytes and cells of the monocyto-macrophage line. These interactions are essential for the penetration of the virus into the cell and participate also in the fusion of infected and non-infected cells which is typical for HIV infection. The outer layer glycoproteins of HIV are immunogenic, however, the antibodies which are formed do not neutralize the virus. It is even probable that antibodies can under certain conditions facilitate the penetration of HIV into cells which have on their surface receptors for the Fc fragment of immunoglobulin, i.e. in the first place into cells of the monocyte-macrophage line. These cells play obviously a key role in HIV infection because they are resistant to the cytopathic action of the virus and during their numerous physiological functions serve above all as cells, presenting antigen to T lymphocytes and thus are repeatedly in close contact with other cellular elements of the immune system and may thus help to spread HIV in the organism. PMID- 2256253 TI - [Use of nonparametric methods in medicine. V. A probability test using iteration]. AB - The authors give an account of the so-called Wald-Wolfowitz test of iteration of two types of elements by means of which it is possible to test the probability of the pattern of two types of elements. To facilitate the application of the test five percent critical values are given for the number of iterations for left sided, right-sided and bilateral alternative hypotheses. The authors present also tables of critical values for up and down iterations which are obtained when we replace the originally assessed sequence of observations by a sequence +1 and -1, depending on the sign of the consecutive differences. The application of the above tests is illustrated on examples. PMID- 2256254 TI - [The effect of stimulated tachycardia on diastolic left ventricular filling in patients with ischemic heart disease]. AB - The authors examined 20 patients with ischaemic heart disease (IHD) by pulsed Doppler echocardiography before and after a load of stimulated tachycardia. The character of left ventricular filling depended on the blood pressure reading in a wedged position only in patients who had an elevated pressure (r = -0.65 and r = 0.81 resp. after a load for A/E, r = -0.62 and r = -0.79 after a load for DT). When the pressure is normal, it declines in a wedged position and the left ventricular filling in early diastole becomes protracted and the ratio of the atrial filling rises (A/E increased after the load p greater than 0.001, DT was protracted after the load p greater than 0.01). This change is due in particular to the protracted relaxation of the heart muscle. When the pressure is elevated in a wedged position, i.e. when the elasticity of the left ventricle declines, the rate of early filling rises and its duration is reduced. This relationship was more marked after the load (A/E after the load declined p greater than 0.01, DT after the load was shorter p greater than 0.001). Examination of the flow through the mitral orifice after a load by stimulated tachycardia makes it possible to differentiate patients with a mild and more severe affection of the left ventricle associated with IHD. It permits also prediction of an increased intraventricular pressure and this to monitor the course of the disease or to evaluate the success of treatment. PMID- 2256255 TI - [Experience with permanent cardiac pacemakers in the East Slovakian Region 1978 1987]. AB - The authors present a group of patients where in the course of the 10-year period of 1978-1987 a permanent pacemaker was implanted. 587 primary implantations were made and 327 exchanges of cardiac pacemakers. The mean age in the group of primary implantations was 70.4 +/- 10.3 years, in the group of exchanges 70.4 +/- 10.6 years. n 98.8% pacemakers VVI and VOO made in Czechoslovakia were implanted. Indications for primary implantation were in 64% atrioventricular block (AV) grade III, in 11% AV block grade II, in 22% disease of the sinoatrial node and in 4% other dysrhytmias. The age category above 60 years accounts for 85.5% in the group of primary implantations. A positive feature is the low incidence of complications of surgical and technical nature. An unfavourable feature is that almost all implanted devices were the simplest single electrode systems where the frequency cannot be adapted and where other parameters cannot be changed. PMID- 2256256 TI - [Recording of monophasic action potentials using a contact catheter in humans. Preliminary report]. AB - Investigations of a monophasic action potential (MAP) at a cellular level in experiments provided basic findings on the course of the electric activity in cells in various cardiac compartments and tissues under physiological conditions and various pathological states and has become an indispensible part of the evaluation of electrophysiological properties of various cardiovascular drugs, in particular antiarrhythmic drugs. A record corresponding to the MAP can be obtained also from the surface of the human endocardium during catheterization by means of a Franz contact catheter. MAP is induced by pressure depolarization after applying the catheter to the endocardium of different cardiac compartments. The objective of the author's preliminary communication is to present the initial experience with the MAP record from right-sided cardiac compartments during a routine electrophysiological examination in five patients at rest, during increasing stimulation of the atria and ventricles and after administration of some antiarrhythmic drugs. The authors evaluated the duration of MAP, the duration of 10%, 50% and 90% repolarization, the MAP amplitude, the activation time, repolarization time and the incidence of spontaneous diastolic depolarization. The recording and evaluation of MAP during the routine electrophysiological examination can contribute to the understanding of the development of arrhythmias, the action of antiarrhythmic drugs and to the evaluation of ischaemic changes of the myocardium. The clinical impact of MAP records is not clear so far and its assessment will call for further experience with this method. PMID- 2256257 TI - [Ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia. Electrophysiologic characteristics and testing of the effectiveness of anti-arrhythmia therapy]. AB - The authors present a clinical and electrophysiological characteristic in two cases of symptomatic sustained ventricular tachycardia (VT) with a QRS morphology of left bundle branch block, refractory to common antiarrhythmic treatment. It was confirmed that the mechanism of this arrhythmia associated with a high risk of sudden death is the reentry phenomenon and the authors analyzed its relationship to arrhythmogenic dysplasia of the right ventricle. In a way uncommon in our literature the authors demonstrate the importance of comprehensive electrophysiological examination in these serious cases and its usefulness in confirming the origin of VT in the right ventricle, its importance for mapping the accurate localization of tachycardia and the investigation of effectiveness of drugs and the evaluation of aptness of non-pharmacological treatment. PMID- 2256258 TI - [A proposal for a standardized protocol for echocardiographic examinations of valvular defects, valve prostheses and atrial septal defects]. AB - The authors summarize in standard protocols the spectrum of possible examinations made by means of a modern echocardiographic apparatus in valvular defects and prostheses and in septal atrial defects. They discuss some evaluations and their practical importance. Standardization contributes towards a comprehensive and more illustrative character and facilitates comparison of findings. A structured concept of the protocol is selected with the perspective of its deposition in a data base of an interactive external computer. The work should serve as a stimulus for discussion in other echocardiographic departments and elaboration of their own working procedure. PMID- 2256259 TI - [Comparison of the therapeutic effectiveness of membrane and centrifugation plasmapheresis]. AB - The authors compared 10 pairs of membrane plasmaphereses on an apparatus A 2008 PF and filter Plasmaflux P 2 with 10 centrifugation plasmaphereses on an apparatus Fenwal CS 3000. They evaluated the effectiveness by changes of plasma concentrations of total protein, albumin, beta 2 microglobulin, IgG, IgA, C3 complement, IgM, circulating immune complexes, urea, creatinine, uric acid, cholesterol, triacylglycerols and the clearance of these substances. Changes of plasma concentrations caused by plasmapheresis with the methods used did not differ in any of the investigated substances. The clearance of membrane plasmapheresis was for all substances higher than when the centrifugation method was used. Among values from which the clearance is determined no difference was proved between the two methods in the volume of exchanged plasma, the concentration of the substance in the removed plasma and its mid plasma concentration during the operation. The higher clearance of membrane plasmapheresis was due to the more rapid plasma exchange. PMID- 2256260 TI - [Use of the computer for the evaluation of platelet aggregation]. AB - The authors describe some methods of evaluation for platelet aggregation. Because the approaches are different, frequently some results of aggregation in pathological conditions differ. The authors give an account of their method of evaluation of platelet aggregation by means of a small personal computer. PMID- 2256261 TI - [Neuroglycopenic syndromes in malignant tumors]. AB - Based on observations of five of own patients the author analyzes the causes of spontaneous hypoglycaemia in malignant tumours and assumes three mechanisms of development: 1. Metastatic affection of the liver reduces the reserves of homeostatically usable glycogen and can reduce also the amount of utilized insulin and glucagon, and this weakens the effectivity of contraregulating hormones. 2. In case of large mesenchymal tumours it is assumed that the cause of hypoglycaemia is the neoplastic formation of IGF II. For these hypoglycaemic states a low concentration of C-peptide, IRI (immunoreactive insulin), absence of response of growth hormone to hypoglycaemia, high IGF II in the tumour and plasma and high mRNA for IGF II in the tumour is typical. 3. In hypoglycaemic states with massive metastases in the liver, high IRI and C-peptide it is assumed the cause of hypoglycaemia is a metastatizing insular tumour or a nes.dioblastoma. In those instances concurrent peptic ulcers (gastrin production) are frequent. PMID- 2256262 TI - [Problems in the early diagnosis and treatment of colorectal carcinoma and adenoma in the aged]. AB - In 1985-1989 in the Bruntal district by means of the test for occult haemorrhage (Haemoccult, Rohm Pharma Co.) a total of 1084 subjects aged 65-86 years were examined. The test was positive in 74 subjects (6.83%). A subsequent coloscopic examination was made in 60 subjects, 81% of those with a positive test. Coloscopic examination revealed 8 patients with carcinoma of the large intestine and 45 patients with an adenomatous polyp. The oncological positivity is thus 4.89% of the tested subjects and 88.33% of those subjected to coloscopy. The carcinoma was evaluated in two cases in the stage Dukes A, in four instances in stage Dukes B, in one case in stage Dukes C and in one case in stage Dukes D. In two patients with carcinoma another adenomatous polyp was found in the large intestine. In 14 patients of 45 with an adenomatous polyp another synchronous adenomatous polyp was detected (31.1%). 43 patients were treated by coloscopic polypectomy. Contemporary possibilities of early diagnosis of colorectal carcinoma in conjunction with effective therapeutic endoscopy are perspective in particular in patients of advanced age. PMID- 2256263 TI - [The applied scientific information aspects of the innovative processes in the activities of the epidemiological health institutions of the Ukraine]. PMID- 2256264 TI - [The diagnosis of ischemic heart disease in coal miners]. AB - Results of consultations carried out at a Regional Cardiological Dispensary in 193 coal miners admitted for ischemic heart disease excluded this kind of pathology in 10.9%. The authors analyze errors in diagnosis of various nosological entities of ischemic heart disease (exertion stenocardia, myocardial infarction, etc.) made in local medical institutions. PMID- 2256265 TI - [The efficacy of the hormonal substitute therapy of adolescents with viral hepatitis A combined with thyroid hypofunction]. AB - Inclusion of thyroidin in the complex therapy of patients with viral hepatitis A and concomitant thyroid pathology accompanied by hypofunction of the thyroid gland produced a positive clinical effect, effected favourably the functional activity of the liver, the immunological and hormonal status. Thyroidin is recommended for wider use in this category of patients. PMID- 2256266 TI - [The characteristics of the blood granulocytes in angina patients]. PMID- 2256267 TI - [The immunomodulating therapy of herpes zoster (a review of the literature)]. PMID- 2256268 TI - [The differential diagnosis of acute intestinal infections]. AB - The authors evaluate contemporary possibilities of clinico-epidemiological and laboratory diagnosis of intestinal yersiniosis in the clinical practice. Data are reported on infestation of the environment with yersiniosis pathogen in this territory and the clinical picture of gastrointestinal form of yersiniosis and its symptomatology that is of help in the diagnosis. Perfection of laboratory diagnosis is of great importance in this respect. PMID- 2256269 TI - [A case of chronic active hepatitis as a sequela of past coli infection]. PMID- 2256270 TI - [Raising the qualifications of infectious disease specialists]. PMID- 2256271 TI - [The level of the professional training of physicians rendering care to myocardial infarct patients at the prehospital stage in the city of Dnepropetrovsk]. PMID- 2256272 TI - [The participation of physicians in the organization of the December armed uprising of 1905 in Gorlovka]. PMID- 2256273 TI - [The use of verapamil in suppositories for treating patients with ischemic heart disease]. AB - A study is presented of 51 patients with ischemic heart disease showing stenocardia of functional classes II-III. The patients received verapamil in suppositories. Cessation or reduced of the frequency of stenocardia attacks were noted after a 10-day course of verapamil (dose--40 mg 3 times daily) in 98.1% of patients. The effect of verapamil treatment was more pronounced in angina pectoris without myocardial infarction in the anamnesis. In IHD patients arterial pressure reduced due to decrease of the general peripheral resistance while the cardiac ejection remained unchanged. The antiarrhythmic effect was more pronounced in atrial extrasystole. Side-effects due to verapamil treatment were not registered. PMID- 2256274 TI - [The effect of a standard breakfast on the central hemodynamics of patients with stenocardia of effort]. AB - Results are reported of a study of the central hemodynamics in 46 patients suffering from ischemic heart disease with effort stenocardia and in 11 clinically healthy persons. In 96.78% of patients with ischemic heart disease and the healthy persons breakfast was followed by an increase of the number of cardiac contractions, minute volume while the general peripheral resistance reduced. These changes are evaluated as a response reaction of the cardiovascular system to an increased inflow of blood to the digestive organs. After breakfast patients with IHD showed an increase of the stroke volume and 3.22% of them showed an unfavourable reaction of cardiovascular system. Planning recommendations on the dietary regimen of patients with IHD one has to consider the character of the cardiovascular system to food loads that may prevent the development of complications. PMID- 2256275 TI - [Pressor-depressor prostaglandins in patients with stage-II hypertension]. AB - The authors investigated the basal level of pressor and depressor fractions of blood plasma prostaglandins in 92 patients with hypertensive disease (stage II) showing a different plasma renin activity and reaction of the prostaglandin system to acute furosemide loads in 27 patients and 16 practically healthy persons. It was found that the hypertensive patients revealed a prevailing pressor fraction of prostaglandins against the background of unchanged depressor prostaglandins. In the healthy stimulation with the saluretic agent resulted in physiological mobility of the system of prostaglandins manifested in a rapid response of the humoral system directed to limitation of fluid and sodium losses. In hypertensive disease, however, there occurred a sharp reduction of the reactive capacity of the depressor system, its exhaustion and inertness. PMID- 2256276 TI - [The physical rehabilitation at a sanatorium of patients wearing aortic valve prostheses]. AB - Methods and results of physical rehabilitation of 81 patients with prostheses of the aortal valve in conditions of a health resort are reported. The authors revealed a 29.2% increase of physical, working capacity and a reduction (8.2%) of oxygen expenditures per unit of work. Increase of intensity of training loads improved the results of physical rehabilitation. The role of health resort treatment in the system of postoperative rehabilitation of patients with heart valve prostheses is emphasized. PMID- 2256277 TI - [The use of vilozen in treating patients with vasculitis of different origins]. PMID- 2256278 TI - [The bactericidal function of the blood neutrophils in myeloproliferative diseases (a review of the literature)]. PMID- 2256279 TI - [The count of the large granule-containing lymphocytes of the peripheral blood and the natural killer activity in patients with malignant tumors]. AB - The authors investigated the quantity of large granule-containing lymphocytes and natural killer activity in donors, in patients with malignant and benign diseases of the lungs, mammary gland and digestive tract at admission to the hospital; 234 examinations were carried out. Results of the investigation revealed an inhibition of the natural resistance in patients with diseases of the mammary gland, lungs, digestive tract. A positive correlation has been revealed between the natural killer activity and content of large granule-containing lymphocytes in donors and in patients at admission. PMID- 2256280 TI - [Indomethacin as a modulator of the activity of natural killer cells (a review of the literature)]. PMID- 2256281 TI - [The characteristics of the course of cholelithiasis in diseases of the cardiovascular system]. AB - The authors discuss the difficulties in diagnosing cholelithiasis. Considering the presence of disorders of the metabolic function of the liver, ultrasound examination is considered the most preferable method of diagnosis of cholelithiasis. Knowledge of the specificity of development and clinical manifestations of cholelithiasis in diseases of the cardiovascular system is of importance due to difficulties of diagnosis and high incidence of this kind of pathology among this group of patients. PMID- 2256282 TI - [A morphometric analysis of tissue homeostasis in peptic ulcer patients during treatment with antihistamine preparations]. AB - The authors carried out a comparative examination of 68 patients with duodenal ulcer receiving monotherapy with cithemidine and a combination of cithemidine and dimedrol. Clinical data indicate that combined use of H1- and H2-histamine blockaders produce a reliable therapeutic effect. Morphological investigations of biopsies from the periulcerous region and morphometry of cellular and noncellular structures showed that the mechanism of this effect consists in strengthening of the mast cell apparatus adding the excess of tissue histamine. PMID- 2256283 TI - [The body oxygen allowance in myocardial infarct patients with progressive forms of acute circulatory failure]. AB - Oxygen supply of the body was studied in 172 patients with macrofocal myocardial infarction with a varying course of acute circulatory insufficiency. It was found that most patients with acute circulatory insufficiency developing during onset of the disease showed latent cardiac insufficiency that can be detected determination of the coefficient of oxygen transport function of the left ventricle. These patients also showed a pronounced shift of oxyhemoglobin dissociation curve to the right and an increase of the peripheral blood flow. PMID- 2256284 TI - [Autotransfusions of sorbent blood in treating peptic ulcer patients with an unfavorable course]. AB - Autotransfusion of sorbent blood was used in the complex treatment of 62 patients with gastric ulcer characterized by an unfavourable course. The course of autotransfusions favoured scarring of the gastric ulcer in 70.9% of patients, normalized the helper/suppressor relations of regulatory subpopulations of T lymphocytes, normalized the indices of natural killer activity. PMID- 2256285 TI - [Intravascular coagulation of the blood in liver cirrhosis (a review of the literature)]. PMID- 2256287 TI - [The intestinal microflora in nonspecific ulcerative colitis]. AB - On the basis of a complex clinical examination of patients with ulcer lesions of the large intestine it is concluded that differential diagnosis of ulcerative colitis should be based no microbiological, serological, immunological, endoscopic methods of examination. Complex conservative treatment should include both routine measures and bacterial agents. PMID- 2256286 TI - [The relationship of cellular and humoral immunity to the reparative process in patients operated on for dolichocolon]. PMID- 2256288 TI - [External respiratory function studied by analysis of the flow-volume loop in patients with acute pneumonia]. AB - The external respiratory function was examined in 141 patients with acute pneumonia on "METATEST" spirographs. All calculations were computerized. It is concluded that use of native spirographs for examination of the external respiratory function by means of the stream-volume loop analysis method widens the diagnostic possibilities and is of value in pathogenetic therapy. PMID- 2256289 TI - [The treatment of patients with chronic bronchitis and bronchial asthma]. AB - The authors analyzed treatment results in 82 patients with chronic bronchitis and 68 patients with bronchial asthma including association of inhalation of humid and dry sodium chloride aerosols with preliminary administration of a broncholytic drug. Improvement of the patients' condition was confirmed by results of functional examinations and data of immunological tests. PMID- 2256290 TI - [Genetic variants of haptoglobin in patients with destructive pulmonary tuberculosis]. AB - Haptoglobin (Hb) phenotyping was carried out in 143 patients with tuberculosis and 221 practically healthy persons. Three phenotypes were distinguished: two homozygotic Hp. 1:1 and Hp. 2:2 and one heterozygotic Hp. 2:1. An analysis of the frequency of distribution of the above-mentioned phenotypes indicates that patients with tuberculosis as compared with the healthy showed a significant reduction of the number of Hp. 2:1 carriers while the number of Hp. 2:2 increased. There was a definite dependence between the haptoglobin phenotype and course of the disease. In carriers of the Hp. 2:1 abacillation of the sputum and closure of destructions occurred earlier than in carriers of Hp 1:1 and, in particular, Hp. 2:2. PMID- 2256291 TI - [The treatment of patients with recurrent pulmonary tuberculosis]. AB - A study is presented of the treatment efficacy of 96 patients with destructive forms of recurrent pulmonary tuberculosis depending on the use of different pathogenetic agents. It was found that in group receiving pathogenetic treatment closure of the destruction caverns increased to 73.7% (53% in the control group) and healing time reduced. PMID- 2256292 TI - [The morphological changes in the neural apparatus of the lungs in experimental hypertension]. AB - Histological investigations were conducted in 75 embryos and fetuses with 10- and 20-days term of embryogenesis obtained from 15 pregnant rats with experimental renal hypertension. It was established employing general biological, enzyme histochemical, impregnation and morphometric methods that short-time hypertension of the maternal [correction of material] body produces delay of growth, development and differentiation of nerve cells and their fibers of the respiratory organs. At the same time by the end of pregnancy separate nerve elements were detected with pronounced signs of high organization and differentiation. This should, apparently, be evaluated as a manifestation of compensatory-adaptative properties of the peripheral nervous system to inadequate conditions developing in the process of embryogenesis. PMID- 2256293 TI - [The Stevens-Johnson syndrome in a female patient with chronic glomerulonephritis]. PMID- 2256295 TI - [A statistical method for the associative analysis of the ultrastructure of spermatozoa]. PMID- 2256294 TI - [The diagnostic criteria of aspermia]. AB - A study is presented of the clinical, endocrinological, morphological indices in 126 patients with sterility. In testicular aspermia the androgenic-estrogenic balance reduced in all kind sterility independent of the clinical signs of hypoandrogenization and degree of disorder of spermatogenesis. A correlative dependence was revealed between the level of follitropin in the blood plasma and degree of inhibition of spermatogenesis in secretory sterility. PMID- 2256296 TI - [The treatment of women with dyshormonal myocardiodystrophy]. AB - Cryogenic treatment in association with thymalin was used in women suffering of dyshormonal myocardiodystrophy associated with hyperplastic processes of the uterus. This treatment proved efficient and furthered significant reduction of disappearance of both extracardiac manifestations of the disease. Under the effect of thymalin indices of cellular and humoral immunity were restored. PMID- 2256297 TI - [Autonomic dysfunction in diabetics]. AB - The authors examined 120 patients with diabetes mellitus of the first and second types. Vegetative dysfunction was revealed in 84 patients (70%) that was manifested in disorders of the vegetative tone, vegetative reactivity. Different tests for assessment of the vegetative status and method of treatment of vegetative dysfunction are described. PMID- 2256298 TI - [The effect of prednisolone on the immunoglobulin content of the blood in patients with disseminated sclerosis]. AB - The authors examined the dynamics of IgA, IgM, IgG in the blood of 100 patients with multiple sclerosis. Of them 50 patients received complex treatment in combination with prednisolone. Comparison of indices of concentration of serum immunoglobulins revealed a distinct reduction of their level of all classes in patients with multiple sclerosis, especially in those receiving prednisolone. Prednisolone produced an unfavourable effect on the course of the demyelinating process in patients with multiple sclerosis. PMID- 2256299 TI - [Cases of progressive supranuclear palsy (the Steele-Richardson-Olszewski syndrome)]. PMID- 2256300 TI - [The intraosseous administration on kavinton in treating myeloradiculoischemia]. AB - The authors present a comparative analysis of the efficacy of their method of administration of vasoactive drugs into the peridural venous system and traditional conservative therapy in radiculomyeloischemia of different etiology. The dynamics of the disease was evaluated both by clinical manifestations and by evoked spinal cord potentials, complex examination of the acid-base balance of the blood from the involved vascular territory and blood from extremities. Results of a detailed examination of 24 patients with myeloradiculopathy carried out by means of precise electrophysiological and laboratory methods permit to recommend this treatment in clinical conditions. PMID- 2256301 TI - [The characteristics of the oxygen-transport function of hemoglobin in myasthenia patients]. AB - A study is presented of the oxygen-transport function of hemoglobin in 50 patients suffering of myasthenia. Age of the patients: from 18 to 70 years. The patients showed increased level of the erythrocytic 2,3-DPG which is a sensitive index of the state of tissue oxygenation and changes of the kinetics of oxygen by hemoglobin. The obtained results permit to evaluate the mechanisms of development of respiratory insufficiency in patients with myasthenia, favours adequate assessment of the severity grades of the disease, help to plan pathogenetic treatment. PMID- 2256302 TI - [The pathomorphological changes in the epiphysis in chronic alcoholism]. AB - Routine, histochemical and morphometric methods were used in examination of epiphyses in 45 autopsy cases of persons that suffered of alcoholism. Characteristic morphofunctional features of the epiphysis were found in those suffering from alcoholism with a stable and hard drinking character, alcohol epilepsy showing involvement of the epiphysis in the complex pathogenesis of the disease. PMID- 2256303 TI - [Fungal lesions of the pharynx]. PMID- 2256304 TI - [Individual sensitivity to local vibration and the prediction of the risk for vibration disease in miners]. PMID- 2256305 TI - [The hygienic mapping of water resources by the degree of pollution]. AB - The author describes a method of designing a map of the Ukrainian SSR (1:150,000) aimed at hygienic cartography of water objects according to their degree of pollution in the large and small rivers of the Ukraine with consideration of the organoleptic toxicological properties and sanitary regimen. Bacteriological indices were not used. PMID- 2256306 TI - [The morphological characteristics of the internal organs of experimental animals fed the meat of hydrobionts]. PMID- 2256307 TI - [Zonographic study of pleural lesions due to asbestos dust]. AB - Results of zonographic examination of the chest were compared with roentgenographic data in 34 patients with asbestos hyalinosis of different severity. The zonographic substrate of pleural hyalinosis are echo-poor intermediate spaces that are visualized bilaterally in different parts of the pleura. It was established that zonographic examination is more sensitive than roentgenography for revealing pleura hardening. Chest zonography is recommended to reveal of exclude pleura hyalinosis induced by asbestos in the absence of typical asbestos-induced changes on the pulmonary x-ray picture. PMID- 2256308 TI - [The treatment and vocational rehabilitation of patients with bronchitis and pneumoconioses working in the mining industry]. PMID- 2256309 TI - [The echocardiographic indices of patients with chronic bronchopulmonary diseases due to exposure to jute, flax and kenaf dusts]. AB - Chronic bronchopulmonary diseases without concomitant diseases in 32 workers contacting with dust of jute, flax, kenaf were not accompanied by abnormal echocardiographic findings. Patients with byssinosis and chronic bronchitis showed a statistically valid increase of the stroke volume indicating potential possibility of functional loads of the myocardium and its structural sequels during advance of bronchopulmonary diseases. PMID- 2256310 TI - [Flow cytometry in virologic research]. PMID- 2256311 TI - [The antibody activity to synthetic C-terminal fragments of the heavy-chain hemagglutinins of influenza virus A subtypes H1 and H3]. AB - C-terminal peptide fragments of the heavy chain (HA1) of influenza virus, subtypes H1 and H3, hemagglutinins were synthesized. Rabbits and guinea pigs immunized with peptides H3 (314-328) and H1 (314-328) conjugates with BSA developed high immune response to conjugated peptides. Solid-phase RIA demonstrated interaction of antisera to peptide H3 (314-328) with A/Aichi/2/68 virus which was inhibited by peptides H3 (314-328) and H3 (317-328) but not by H3 (320-328), that is, antibodies interacted predominantly with amino acids 317-323 HA1. Anti-H3 (314-328)-BSA showed a marked activity in H1 and NT with a number of H3 subtype viruses. Antisera to peptide H1 (314-328) reacted with A/PR/8/34 virus insignificantly and were also inactive in H1 and NT with subtype H1 viruses. PMID- 2256312 TI - [Functional activity of glycoproteins from interepidemic isolates of the influenza virus]. AB - The results of the study into the function of glycoproteins of influenza viruses isolated in the 1987 interepidemic period. Natural isolates were found to have virus particles with deficient neuraminidase activity but retained hemolytic and infectious activity. Biological sequences of the lack of neuraminidase activity in the isolates consisted in disorders of sialic acid metabolism in the infected cells, blocking of the receptor site of hemagglutinin and increased sensitivity to inhibitors. It is assumed that the interepidemic virus isolates represent a biologically heterogeneous population in which particles with deficient neuraminidase activity are prevalent. PMID- 2256314 TI - [A trial of a cultured inactivated vaccine against hepatitis A on Saguinus mystax tamarins]. AB - An experimental batch of inactivated hepatitis A vaccine was prepared using hepatitis A virus (HAV), HAS-15 strain, adapted to cell culture and purified by ultracentrifugation. The vaccine was tested in tamarins immunized intramuscularly three times one month apart. Three tamarins received a vaccine preparation containing 10 ng of immunogen each, three--100 ng each, and three animals were used as controls. The efficacy was judged by the anti-HAV antibody response in the vaccinated animals and development of immunity to subsequent virus challenge two months after the last immunization. The criteria of infection were: elevation of serum alanine aminotransferase, fecal excretion of HAV and production of specific antibody of IgM class. The immune response to 10 ng of the immunogen was lower than to 100 ng, however, both doses produced complete resistance to infection. The booster effect was observed in animals receiving 10 ng of the immunogen. The vaccine batch under study in the indicated doses was shown to have a good immunogenic potency and protective activity for tamarins. PMID- 2256313 TI - [The detection of the influenza virus in the small intestine in diarrhea in piglets]. AB - Electron microscopy used for examinations of small intestine suspensions of piglets in the prenatal and postnatal periods allowed influenza virions to be identified in virus population. An attempt was made to preserve the discovered population in alternating animal--cell culture--animal passages. Serological examinations of the swine herd confirmed the circulation of influenza viruses in the herd. PMID- 2256315 TI - [Screening of sera from the adult populations of some USSR regions for antibodies to the human T-cell leukemia virus type I (HTLV-I)]. AB - The results of serologic survey of 4118 residents of the USSR Far East from 16 to 82 years of age and 1037 blood donors for antibody to HTLV-I by the method of passive agglutination of gelatin particles coated with viral proteins are summarized. The portion of HTLV-1 seropositive subjects in the Khabarovsk Territory was 1.79% (25 out of 1391), in the Maritime Territory 2.2% (18 out of 801), in the Sakhalin Island 1.6% (26 out of 1557), and in Kamchatka 1.6% (6 out of 369). A discrete area of a higher number of positive cases was found among Nivkhi national group in the village of Nogliki in the Sakhalin Island: 6.4% (10 out of 155). In women, antibody to HTLV-1 was found twice as frequently as in men. Seropositives to HTLV-1 among blood donors in Moscow, the town of Komsomol'sk-na-Amure, and the town of Yuzhno-Sakhalinsk comprised 1.4%, 1.6%, and 5.45%, respectively. The occurrence of HTLV-1 infection among the normal population of the Far East and especially among blood donors attests to the expedience of wider seroepidemiological surveys of the population and especially donors for HTLV-I infection in other regions of the USSR as well. PMID- 2256316 TI - [The geographical spread of enterovirus uveitis in the USSR]. AB - Enteroviral uveitis is accompanied by intensive and long-term production of specific neutralizing antibodies. The antibody titer to the causative virus ECHO 19/K (Siberia, Krasnoyarsk, 1980-1981) was 1:1000-1:65,000 in 80% of children 5 to 6 1/2 years after the illness. In retrospective examinations of blood sera from children with the history of uveitis using a neutralization test with ophthalmotropic strains of ECHO 19 and ECHO 11 viruses, the ECHO-virus etiology of this disease was first established in 80 patients living in the European part of the country (Moscow, Leningrad, Volgograd, Krasnodar, Donetsk, etc) and in the Caucasus (Yerevan, Tbilisi, Baku). The epidemic process in uveitis is associated with the emergence and alternation of antigenic ECHO virus variants. Both in the Asian and European USSR the causative agent of uveitis in 1979-1983 was ECHO 19/K, in 1980-1987 ECHO 11/A, and in 1986-1989 ECHO 11/B virus. In 1979-1989, altogether over 800 cases of uveitis in children caused by ophthalmotropic variants of ECHO 19 and ECHO 11 viruses were detected in the Soviet Union. PMID- 2256317 TI - [The cultivation and physicochemical properties of the Josiah strain of the Lassa virus]. AB - Data on the stability of Lassa virus, Josia strain, isolated from man to the effect of physicochemical factors (heating at 50 degrees C, solutions of urea and formalin of various concentrations, UV irradiation) as well as on the time course of this strain reproduction in cell lines of different origins are presented. Recommendations for lowering of reactogenicity of the virus-containing material are given. The experimental results must be taken into consideration in the development and manufacture of diagnostic and therapeutic-prophylactic preparations for Lassa fever. PMID- 2256318 TI - [Viral retrograde-like pattern of neuronal degeneration in experimental amyotrophic leukospongiosis]. AB - The pattern of destructive alterations of neurons and their processes at different spinal cord levels in guinea pigs with experimental amyotrophic leukospongiosis (AL) was studied by light and electron microscopy. The destruction of a portion of neurons was found to be of retrograde degeneration type. Electron microscopy of spinal conduction pathways showed that degenerative alterations occurred not only in the neuronal soma or processes but also in synaptic structures. The results indicate primary involvement of nerve cell processes, particularly axons, in experimental AL. It is suggested that AL pathogenesis is pathomorphologically based on the uptake of the agent by axonal terminals. PMID- 2256319 TI - [Radioimmunologic analysis for the rapid diagnosis of arbovirus infections]. AB - The employment of radioimmunoassay (RIA) allows arbovirus infections to be diagnosed at an early stage of the illness. In the present study the best variant of RIA was determined with regard to its practical use in rapid diagnosis of some arbovirus infections and its superiority over CFT, HI, IHA, IF. The method was shown to be highly specific and sensitive for qualitative studies of specimens from natural foci of arboviruses and for timely diagnosis of human illnesses. PMID- 2256320 TI - [The antiviral activity of a number of Soviet chemical preparations and the interferon inducer larifan and their combinations in a model of experimental genital herpes in guinea pigs]. AB - Chemical drugs and the Soviet interferon inducer larifan as well as their combinations were evaluated in genital herpes in male guinea pigs. Among the chemical drugs tested, the highest efficacy was observed with 2% phosphonoformic acid trisodiate ointment (its therapeutic effect 62%). The efficacy of 2% cycloguanosine ointment and 0.5% phosphonoacetic ointment did not exceed 43% and 36%, respectively. Topical and systemic use of the interferon inducer larifan produced a marked therapeutic effect (63%). Combined use of purophosphate and cycloguanosine analogues was more effective than the agents alone, yet the effect of the combinations being nothing more than additive. PMID- 2256321 TI - [Vaccinia virus stimulation of oncogenesis in C57Bl mice]. PMID- 2256322 TI - [The use of monoclonal antibodies for the rapid detection of the hemagglutinin of the influenza A virus (H2N2) and its antibodies]. PMID- 2256323 TI - [A new slow infection]. PMID- 2256324 TI - [The social role of physicians]. PMID- 2256325 TI - [Prevention of hepatitis B by passive immunization of children with chronic hematologic disease immunoglobulin]. AB - In order to prevent the hepatitis virus B (HBV) infection, in 66 children aged from 6 months to 14 years with acute and chronic leukaemias, Hodgkin's and non Hodgkin's lymphomas, testicular tumours, and aplastic anaemia a specific immunoglobulin was used intravenously (Hepatect made by Biotest). Hepatect was given every month to children with proliferative diseases throughout the whole time of intensive chemotherapy, and to children with aplastic anaemias during the administration of antilymphocytic globulin, prednisone, and Anapoln. Fourteen children were excluded from the analysis due to lack of systematic follow-up. Among 52 studied children, in most cases considerable fluctuations were observed of antibody concentration, the maximal values of which were of 150 mIU/ml. In 35 children, with the exception of sporadic falls, the anti-HBs antibody level remained level was noted, in two cases the presence of antibodies was revealed only sporadically. One of these children was infected with HBV. In all, three children were infected (5.76% of all children in the studied group). Perhaps the use of higher doses of Hepatect and its more frequent administration in children showing low anti-HBs level after routine doses might reduce further the incidence of infection. PMID- 2256326 TI - [Hepatitis B in children with leukemia and lymphoma]. AB - In the time period from February to October 1988 the indicators of hepatitis virus B infection, transaminase activity, and bilirubin level were studied in 89 children with acute leukaemias and malignant lymphomas. The age of the children was from 7 months to 16 years. Fifteen children were examined before starting the treatment with cytostatics, 48 during intensive chemotherapy, and 26 during maintenance treatment. HBV markers were found in 53 children during intensive therapy and maintenance treatment. Out of 36 children with negative HBV infection markers 31 were examined before starting the treatment with cytostatics or during the first 6 months of treatment. Nine out of 53 children in whom HBV infection markers were found had aminotransferase activity raised over 100 u/l and/or bilirubin level over 5 mg/dl and in nine cases transaminase activity and bilirubin level were raised only slightly (below 100 u/l and below 5 wg/dl). In 53 children the results were normal. The high incidence of HBV infection in children with acute leukaemias and lymphomas indicates the necessity of routine prophylactic treatment in this group of patients. PMID- 2256327 TI - [Osteomyelitis of the maxilla in children]. AB - Seven cases are presented of maxillary osteomyelitis in children aged from three weeks to seven years. On the average the treatment lasted 24 days. In five children no complications or recurrences of the disease were observed. In two cases after several days disease recurrence developed in form of local changes. No complications were noted. During treatment a positive effect of linkomycin was observed in this disease. PMID- 2256328 TI - [Education of health personnel for promotion of breast feeding--pilot studies. II -Attitudes]. AB - The study was carried out for investigating the attitudes towards breast-feeding among doctors, nurses, and midwives working in primary health service units providing care for mother and child in certain areas. Generally the attitudes were found to be positive. However, a great part of the studied personnel did not identify themselves with the possibility of actual activity for breast-feeding in their professional role. The necessity was stressed of a more precise outlining of the duties of various groups of health service workers and incorporation of activating mechanisms into it. PMID- 2256329 TI - [Selected determinants of fear before visiting doctor's office]. AB - Using the Gottschalk-Gleser method the level of fear was measured in laryngological patients (a group of 60 patients) before visit to doctor's office (before the patient entered the office) and then using an interview form designed by us information was obtained on factors from the past of the patient which could have affected his/her present level of anxiety felt before the visit. The results indicate that definite experiences of the patients connected with the doctors and diseases in the past increaser the present level of anxiety. PMID- 2256330 TI - [Campylobacter pylori--its role in diseases of the upper digestive tract. The present and future]. AB - In the paper an outline of modern knowledge is presented on Campylobacter pylori (Helicobacter pylori) which participates in certain upper digestive tract diseases. The history is described of studies on this organism and modern methods of its identification are discussed. The sites of presence of this microorganism are presented in the upper part of the digestive tract and the diseases of this part of the digestive tract are described which are associated with the presence of Campylobacter pylori. The methods of treatment are mentioned in patients infected with this organism, with the criteria of treatment effectiveness. PMID- 2256331 TI - [The renin-angiotensin-aldosterone (RAA) system in endocrine diseases]. AB - Modern, views are presented on the pathogenesis of arterial hypertension in certain diseases of endocrine glands. In patients with phaeochromocytoma, virilizing tumours, acromegaly, in Cushing's disease, and in Conn's syndrome at the present state of knowledge it is not possible to formulate unequivocal conclusions concerning the effects of renin-angiotensin-aldosterone system on the mechanism of arterial hypertension development in these endocrinopathies. PMID- 2256332 TI - [Weil's disease complicated by subarachnoid hemorrhage and myocardial infarction]. AB - A case of Weil' disease is described in a 32-year-old patient complicated by subarachnoid haemorrhage from ruptured cerebral aneurysm and anterolateral myocardial infarction. The differentiation of the complications in strict meaning of the word from inflammatory and toxic changes in the course of leptospirosis is often difficult. PMID- 2256333 TI - [Thromboangiitis obliterans of cerebral vessels]. PMID- 2256334 TI - [A case of Munchausen syndrome]. AB - A case is described of the Munchhausen's syndrome in a 35-year-old female patient. The patient was hospitalised 17 times and had six laparotomies for suspected peritonitis. Besides that venesection and lymphography were done. The patient malingered also insulin-dependent diabetes, fever, and haematuria. Since she worked as a housemaid for a doctor she had access to textbooks and professional literature. In the paper more modern aspects of the Munchhausen's syndrome are also discussed e.g. the Munchhausen's syndrome "by proxy". PMID- 2256335 TI - [Trypsin and alpha-amylase activities in the pancreas of guinea pigs. II. Effect of per os and intra-intestinal infection with invasive ova of Ascaris suum]. AB - The guinea pigs were infected orally or intraintestinally (after laparotomy) with 5000 invasive eggs of Ascaris suum. On the 7th day after infection the invasion was controlled by lung's weight, degree of congestion, and number of larvae in the lungs. The activity of amylase was determined according to Fennel method, trypsin to Anson method. The activities of both enzymes in pancreas of orally infected animals (after laparotomy or not) were lower, and relative weight of lungs of these animals was higher than in control animals. In pancreas of guinea pig with invasive material introduced into its, the activities of amylase and trypsin were higher than in control animals, but only the activity of trypsin differed significantly. PMID- 2256336 TI - [Large-intestinal nematoda in bison]. AB - In the Bialowieza Forest the parasitological autopsy of large intestine of 6 bisons was made at the beginning of winter of 1987-1988, and 9 dissections were made in the latter part of both seasons. Four species of nematodes were found to occur together: Chabertia ovina, Oesophagostomum radiatum, Oe. venulosum and Trichocephalus ovis. At the end of wintering in bisons the invasion of Ch. ovina appeared in high percent of animals, but the intensity of it was low. However, the extensity and intensity of invasion of three remaining species of nematodes distinctly arose. In comparison with bisons in closed reserves, free living bisons assimilated Oe. venulosum and Ch. ovina. It is likely that the winter quarters are the source of invasion. It can be explained by the permanent accumulation of feaces with invasive forms of nematodes, and by feeding bisons on the great amount of hay, in which the invasive forms of nematodes may also occur. PMID- 2256337 TI - [Ultrastructure of the head surface of selected Bovicolidae (Mallophaga, Ischnocera)]. AB - On the basis of morphological examinations of the head of Bovicola caprae, Cervicola meyeri and C. tibialis, carried out in the scanning electron microscope, the species descriptions received up to now, were supplemented with new characters. An attention has been paid to rather primitive type of antennal sesilla coeloconica (with developed cone) as well as the lack of accompanying pore organs, characteristic also of other Ischnocera. PMID- 2256338 TI - [The mite Varroa jacobsoni Oudemans, 1904 on larvae of common wasp Vespa (Paravespula) vulgaris L]. AB - The nest with living wasps in Swarzedz was destroyed on 5th September 1988. Three adult females of Varroa jacobsoni were found on larvae of Vespa (Paravespula) vulgaris. It was the first record of the occurrence of V. jacobsoni in V. (P.) vulgaris colony in Poland. PMID- 2256339 TI - [Trypsin and alpha-amylase activities in the pancreas of guinea pigs. III. Effect of homogenates of invasive ova of Ascaris suum and organic acids C2-C6 on the activity of enzymes in pancreatic extracts]. AB - The studies were carried out on pancreas extracts from guinea pigs free of parasite invasion. The activity of trypsin was determined according to the method of Anson, and amylase of Fennel method. The measurements of activity were done at the presence of homogenized invasive eggs of Ascaris suum, and the mixture of volatile organic acids C2-C6 (at concentrations of 30.3 and 0.3 mM/l). In samples with homogenized invasive eggs of A. suum the amylase activity remained unchanged while the activity of trypsin was considerably higher (p less than 0.01). The introduction of the organic acids at conc. 30 mM/l into the samples was the reason of lower amylase activity. No influence of these acids on trypsin activity in pancreas extracts was observed. PMID- 2256340 TI - [History of the Pharmacology Institute of Vienna University (foundation difficulties, researchers' personalities and selection of achievement goals)]. PMID- 2256341 TI - [Cardiovascular pharmacology. An example of the need of clinically relevant pharmacological research]. AB - Like all other scientific disciplines, preclinical pharmacological research is subject to permanent changes. New measuring devices and the possibility of continuous on line data acquisition have markedly influenced basic research in this field. Another aim of modern cardiovascular pharmacology is the testing of promising drugs in clinically relevant animal models of disease, particularly under conditions, referring to the everyday situation in patients, e.g. physical activity. Investigations carried out in this way allow an exact assessment of the clinical efficacy of new drugs, and are, thus, clearly indispensable, also from the ethical point of view, before primary evaluation of the drug in man. PMID- 2256342 TI - Progress symposium--progress in plastic and reconstructive surgery during the last decade. PMID- 2256343 TI - Progress in the treatment of congenital malformations of the hand. AB - Treatment of congenital malformations of the hand and forearm has progressed not only from new procedures, but especially due to a new technique, namely microsurgery. Microsurgery enables skilled hand surgeons to operate on the tiny hands of babies without damaging the anatomical structures. The optimal time for the correction of many deformities is during the first 2 years of life. This gives excellent adaptation of the corrected structures to their altered function, especially in combination with a long period of further growth. Several new procedures are described which have been made possible only since the introduction of microsurgery, either by microvascular anastomoses or by meticulous dissection technique (toe transplantation, proximal toe phalanx transplantation, nail wall formation in complex syndactyly, transposition of digital parts in polydactyly and radial club hand). PMID- 2256344 TI - New aspects of craniofacial surgery. AB - The concept of craniofacial surgery, introduced by a French plastic surgeon named Paul Tessier, has completely transformed the treatment of facial deformities affecting the skeleton. Two of the more spectacular operations are correction of teleorbitism by orbital mobilization, and correction of facial retrusion by facial or fronto-facial advancement. These operations have evolved with the bipartition principle and the monobloc and splitting techniques. Craniofacial techniques applied in infancy for correction of craniosynostosis have proved very successful in most cases. The increasing use of miniplate fixation and utilization of cranial bone grafts are mentioned, as well as advances made in genetic and fetal diagnosis. PMID- 2256346 TI - Functional reconstruction after facial paralysis: a survey. AB - The attempt to achieve symmetrical harmonious facial expression represents a complex surgical challenge, necessitating an individualized approach. Clinical investigations and laboratory experiments have demonstrated how to better reconstruct a "smile." In long-standing deformities, ipsilateral or crossfacial nerve grafting followed by functional muscle transfer in a 2-stage procedure seems to give the most acceptable results; however, hypoglossal-facial anastomosis and dynamic muscle techniques such as temporal muscle transposition and others can result in adequate functional reconstruction. The development of these techniques with special emphasis on those made during the last 10 years is discussed and compared with our own experiences. PMID- 2256345 TI - Progress in peripheral nerve reconstruction. AB - The development of peripheral nerve surgery over the past 15 years has been fascinating to watch. Significant improvements have been achieved by the wide application of techniques which were developed before this period. New approaches may revolutionize the tactics of nerve repair in the near future. PMID- 2256347 TI - Reconstruction of traumatically acquired defects of the phallus. AB - Trauma to the male phallus may be treated in a systematic approach to achieve aesthetically and functionally pleasing results. Isolated burns should be treated early with excision and preputial flap or skin graft closure. Avulsion injuries are closed primarily or skin grafted. Subtotal loss can be treated with penile lengthening techniques. Total loss is treated with reimplantation or microvascular free tissue transfer phalloplasty. There are reconstructive surgical options, instead of penectomy, in patients with penile malignancies. PMID- 2256348 TI - Breast reconstruction: progress in the past decade. AB - There have been numerous advances in breast reconstruction techniques of the past decade. The disappearance of the radical mastectomy along with the increased frequency of smaller tumor detection have contributed significantly to these changes. Furthermore, reliable studies have shown that breast reconstruction does not interfere with extirpative surgery or delay postoperative adjuvant therapy if indicated. Studies such as these have led increasing numbers of women to elect immediate breast reconstruction as opposed to delaying that reconstruction for months or even years after the tumor extirpation. The advent of successful breast reconstruction using autogenous tissue provided the most radical change to reconstructive techniques over the past 10 years. The TRAM (transverse rectus abdominis myocutaneous) flap was the first of these techniques to be introduced and has rapidly assumed a position of prominence among those techniques chosen for breast reconstruction. The LTTF (lateral transverse thigh flap) and the buttock flap, while requiring microsurgical technique, are important alternatives for those patients who choose autogenous tissue breast reconstruction and should be presented to women during the discussion of alternatives for breast reconstruction. Implant technology has continued to improve with the introduction of the tissue expander, the most important addition in the past decade. Investigations are currently underway to provide a long-term tissue expander that does not have to be removed and replaced by a permanent implant. The ultimate end result would be to create a more normal breast shape without firmness. And the use of stacked or directional expanders may allow more freedom in creation of the new breast shape to conform to the opposite side. Finally, nipple areola reconstruction has improved significantly as the tissues of the breast mound itself are used for the new nipple and areola, thereby avoiding the transfer of grafts from distant sites which do not generally maintain their size or projection over time. PMID- 2256349 TI - Progress in flap surgery: greater anatomical understanding and increased sophistication in application. AB - An introduction summarizes the history of the development of flap surgery and puts the discovery of the fasciocutaneous flaps into historical perspective. The anatomical work underlying this discovery is presented and the way in which it has led to improved designs of flaps on the limbs is then described. Finally, the increased refinement and sophistication in the application of all types of flaps is demonstrated by a description of recent advances in the use of microsurgical free tissue transfer in 3 key areas of reconstructive surgery. PMID- 2256351 TI - Progress in limb and digital replantation: Part A--Introduction. PMID- 2256350 TI - Progress in free tissue transfer. AB - The development of microsurgical techniques has supplied plastic surgery with a new chance to transfer tissue to nearly any recipient site of the body. Classical methods still have their value but also their limits in many circumstances. Free tissue transfer has proved its advantages, especially in covering defects in the lower extremity; but microsurgical flaps also gain ground in reconstructive surgery of the head and neck, the female breast, the abdominal wall, and the hands. This article will survey well-classified microsurgical flaps, their indications, and their limits. In addition to a description of skin, fasciocutaneous, septocutaneous, and musculocutaneous flaps, we also include the latest detailed knowledge of free transfer of muscles, vascularized tendons, nerves, bones, and even joints, digits, and jejunal transfer. An outlook toward new perspectives with so-called prefabricated flaps will also be discussed. PMID- 2256352 TI - Progress in limb and digital replantation: Part B. AB - Progress in micro- or macroreplantation has resulted in higher survival rates of formerly amputated parts. Progress has been made as a result of intensive laboratory training and considerable experience due to the popular application of microsurgical techniques. More amputated digits or limbs may survive because the time of ischemia can be exceeded in using cold storage or perfusion. Homo- or heterodigital vessel transposition, expanded indications for vein graft interposition, as well as heterotopic transplantation allow for extremity preservation even in crush injuries, and in disastrous multiple amputations combined with contusion or avulsion. Nowadays, microvascular digital replantation with vessel anastomosis distal to the distal interphalangeal joint in adults is technically feasible. Finger amputations in children are a prime indication for replantation. Maintenance of extremity length is possible in applying external fixation. Emergency free flaps or compound tissue transfer under the "Urgence differee" condition may provide reliable soft tissue coverage. Secondary reconstruction with regard to bone defects, tendon repair, and eventual nerve grafting have to be aspired, finally leading to an improvement of functional results in daily and leisure activities as well as in early professional readaptation. PMID- 2256354 TI - Advances in aesthetic surgery. AB - The evolution of aesthetic surgery began centuries before the birth of Christ. Since Sushutra's first attempts, surgeons still try to achieve or reconstruct the perfection of individual beauty. Surgeons who are engaged in this field of plastic surgery are called cosmetic or aesthetic surgeons. Aesthetic surgery is not just a specialization concerned largely with the removal of the outward signs of aging, nor is it limited to plastic surgery for improvement by restoration of damaged areas of skin and removal of blemishes. Aesthetic surgery crosses the dividing line between surgery for reconstruction and alteration of deviations (which do not in themselves constitute objective deformities) and is sometimes even performed without medical indication, but just for the gratification of individual vanity. This article summarizes the progress of aesthetic surgery during the last decade in some aspects of the field and tries to estimate its' lasting value. PMID- 2256353 TI - Progress in burn treatment and the use of artificial skin. AB - Recently improved survival from thermal injuries has been demonstrated both in children and adults. This increase in burn injury survival rates is the result of multiple changes in treatment; probably the most important changes are, first, a more aggressive management of the wound with prompt excision of devitalized tissues and immediate closure of the wound, and, second, a better understanding and management of metabolic, immunologic, and nutritional aspects of the injured patient. Artificial skin is a very important additional treatment modality that has more recently become available and promises to contribute significantly to improvements in wound management and survival rates by its ability to physiologically close a burn wound immediately after its excision. PMID- 2256356 TI - Papillary thyroid carcinoma: the new, age-related TNM classification system in a retrospective analysis of 199 patients. AB - The new, age-related TNM classification system of papillary thyroid carcinoma was applied in a retrospective analysis of 199 patients operated on during the 24 year period from 1956 through 1979 at the Second Department of Surgery, Helsinki University Central Hospital. According to the new staging system, 103 patients (under 45 years of age) and 96 T1 patients (45 years of age and older) were categorized into stage I. The incidence of carcinoma-positive cervical lymph nodes was highest among patients under 30 years of age at primary surgery. During the follow-up period of 6-29 years, cervical lymph node involvement was verified at reoperation in 20 patients (10%). Distant metastases (bone or lung) developed in 11 patients (5.5%). Thirty-one patients (16%) died from carcinoma. The prognostic value of stage grouping, in terms of metastatic tendency and cancer mortality, was clearly demonstrated in the present material, suggesting the suitability of this simplified, new, age-related staging system in clinical practice. PMID- 2256355 TI - Premature death in patients operated on for primary hyperparathyroidism. AB - To investigate long-term survival after operation for primary hyperparathyroidism, a follow-up study was performed on 896 consecutive patients in whom this diagnosis had been clinically and microscopically verified. These patients were operated on in the years 1953-1982. Their mean age at operation was 57.3 years [standard deviation (SD) 13.1], overall cure rate was 97.0%, and postoperative mortality was 0.89%. Follow-up was 99.8% complete by the end of 1986. Mean follow-up time was 12.9 years (SD: 6.1). Two-hundred ninety-four patients were deceased, which was 118 more than in a control group (p less than 0.001). The latter was based on Swedish population statistics, matched for age, sex, and calendar year. Each year, the control group was the same size as the hyperparathyroid population. The risk of premature death remained increased (p less than 0.001) even after exclusion of poor-risk patients having their hyperparathyroidism diagnosed when being treated or followed because of other serious diseases. The main causes of premature death for the hyperparathyroid patients were cardiovascular and malignant diseases. Both occurred more often than in the control group (p less than 0.001). The results demonstrate that primary hyperparathyroidism causes damage that is not reversed by surgery. PMID- 2256357 TI - Deep leg veins as femoropopliteal bypass grafts. PMID- 2256359 TI - [The clinical and serological characteristics of early congenital syphilis today. 2]. AB - Examinations of 207 children suffering from early congenital syphilis have revealed a lowered incidence of involvement of the bone system, liver, and spleen. Syphilitic rhinitis, chorioretinitis, and orchitis are less frequently recorded. Wassermann's test has been negative in 7.24 percent of patients. PMID- 2256358 TI - Long-term results of a randomized trial of hyperthermic limb perfusion (HLP) with chemotherapy for extremity melanoma. PMID- 2256360 TI - [The characteristics of the immune response to Chlamydia antigens in patients with Reiter's disease]. AB - Immunologic tests (complement fixation, microprecipitation reaction, leukocytic agglomeration phenomenon, leukocyte migration inhibition tests) with standard chlamydial antigen were used in examinations of 116 male patients with Reiter's disease, 54 of these with the first (early) and 62 with the second (late) stages of this process. The findings evidence a higher intensity of antichlamydial humoral and cellular immune response in the patients with the first stage of the disease and a much lower intensity of those with the second stage. The pathologic process in patients with the second stage is liable to a prolonged self maintaining course and is torpid to anti-infection therapy, as against that in the patients with the first stage of the condition; this fact prompts a conclusion that such a course of the process is explained not so much by the infectious agent, as by immune inflammation. PMID- 2256361 TI - [The ultrastructure of anaerobes isolated from the urogenital tract of women]. AB - Electron microscopic (ultrathin sections) examination of culture strains of vaginal Gardnerella and bacteroids isolated in aerobic conditions from urogenital tract of women suffering from Gardnerella infection was carried out. Structural analysis of the bacteria is presented, i.e. their shape, size, morphology, and features of multiplication. PMID- 2256362 TI - [The mastery of the elements of professional activities in the process of the student performance of independent work in a department of skin and venereal diseases]. AB - The authors sum up the experience gained by the chair for skin and sexually transmitted diseases in training the students within the frames of a universal methodological system in accordance with their future specialization as therapists, pediatricians, dentists, or sanitary physicians. The purpose and motivation of training are defined, basic knowledge of the students are checked up, and the contents of students' self-training presented. Written control tests are described, intended to check up the knowledge and skills; these tests include questions in basic theory, treatment and diagnosis strategy, and prophylactic measures used in prevalent skin and sexually transmitted diseases. Such training organization promotes high-quality mastering the profession and adapts the students to physicians' daily routine. PMID- 2256363 TI - [The combined treatment of psoriasis using curative factors from the Sea of Azov]. AB - A total of 319 psoriasis patients were treated at the Interdistrict Rehabilitation Center for Skin Diseases. Multiple-modality treatment making use of therapeutic factors of the Sea of Azov (sea water, liman and sea muds, solar or UV irradiation, mineral water) and (in some cases) drugs was employed. The suggested method of differentiated therapy in summer and autumn-winter has brought a manifest therapeutic effect, was conducive to regression of the clinical symptoms, to normalization of concomitant abnormalities of the gastrointestinal tract, liver, hematologic, biochemical, and immunological parameters. Such therapy resulted in prolongation of remissions, shortening of the treatment terms, and a more benign course of the disease, particularly so after repeated courses administered for 2-4 years. PMID- 2256364 TI - [The experimental skin-resorptive action of furfural and a distillate of D-11 mineral oil]. AB - Animal experiments have revealed manifest skin resorptive effect of furfural. Acute experiments have demonstrated manifest toxic action of furfural when applied to intact animal skin. Subacute action of mineral oil induced poorly manifest toxic effect manifesting as nonspecific visceral changes. PMID- 2256365 TI - [The function of the autonomic nervous system in women with androgenetic alopecia]. AB - Essential shifts in the autonomic nervous system, detectable by clinical methods and during a dynamic examination (of the autonomic reactivity and autonomic activity provision) were revealed in women suffering from androgenetic alopecia. The status of the autonomic nervous system was analyzed with consideration for the effects of psychogenic factors and the type of hair loss. The findings will help develop approaches to treatment of the condition. PMID- 2256366 TI - [The sociomedical efficacy of the enzyme therapy of gonorrhea patients]. AB - The study has involved 3702 male patients with gonorrhea. Of these 62 percent were fresh cases, 38 percent chronic ones; there were 218 patients (5.9 percent) with recurrences, of these 63.3 percent with new relapses and 36.7 percent with chronic ones. 85.3 percent of patients developed monorelapses. The recurrences were equally frequent after antibiotic therapy (50.2 percent) and after combined treatment (49.8 percent). Proteolytic enzymes (chymotrypsin, trapsin 5 mg twice daily with a 12 hrs interval) in combination with an antibiotic were administered to 242 patients with gonorrhea complicated by epididymo-orchitis and with gonorrhea relapses. Etiologic cure was achieved in all of them; postgonorrheal conditions were recorded in 6-7 percent and depended on the antibiotic administered; in reference patients recurrences were recorded in 4.2-6.5 percent of cases, postgonorrheal conditions in 14-21.4 percent of cases. Enzymic therapy helped reduce the length of inpatient therapy of a patient by 5.93 days on an average in cases with orchidoepididymitis and by 14.64 days in gonorrhea relapses, with the economic effect per worker being 131.4 and 307.2 rubles, respectively. PMID- 2256367 TI - [The characteristics of the clinical course of Devergie's versicolor pityriasis ruber pilaris]. AB - A clinical classification of lichen ruber pilaris is presented, based on the authors' observations of 30 cases. Three types of such lichen may be distinguished, characterized by a specific clinical picture, course of skin process, and prediction of the process course: adult, childhood, and atypical types. PMID- 2256368 TI - [A case of combined multiple leiomyomas of the skin and psoriasis]. AB - A 28-year-old patient is described, suffering from disseminated psoriasis and multiple leiomyomas of the skin. This case is of particular interest because of a rare combination of these two conditions. Leiomyomas in this case were effectively treated by laser exposure. PMID- 2256369 TI - [The photochemotherapy of Hailey-Hailey disease]. AB - The results of photochemotherapy of 5 patients with chronic benign familial pemphigus are described. Standard scheme with puvalen and PUVA-22A chamber (Finland) were employed. A course of inpatient treatment consisted of 10-25 irradiation sessions followed by outpatient maintenance photochemotherapy (once a week or two). Erosions and fissures started epithelializing after 8-12 irradiation sessions. A remission of up to 19 months was achieved in all the patients; it was more manifest and durable than after treatment with other schemes. PMID- 2256370 TI - [The ulcerative form of skin sarcoidosis]. AB - A female patient suffering from the ulcerative form of skin sarcoidosis is described and the literature dealing with this problem is reviewed. Peculiar features of this case are described: ulceration of the nodes, which is an extremely rare phenomenon; no involvement of other organs, lungs included, was detectable, which is not typical of ulcerative sarcoidosis; small-nodular elements are parallelled by nodes (Boeck's small-nodular sarcoid and Darier Roussy's subcutaneous sarcoids) in this patient, this evidencing an uniform pathologic process in the skin and subcutaneous fat. Ulceration in this patient is explained by the development of allergic vasculitis of the immediate hypersensitivity type (leukocytoclastic vasculitis and manifest increase of the level of circulating immune complexes). Prednisolone therapy has resulted in an excellent clinical effect. PMID- 2256371 TI - [The immunomodulating action of interferon preparations. The effect of medicinal alpha-interferon preparations on the rosette-forming activity of human blood lymphocytes]. AB - Effects of alpha-interferon (alpha-IF) medical preparations on human blood lymphocyte rosette-forming activity was under study. Blood samples from 40 donors and 81 patients with chronic pyoderma, lupus erythematosus, and pemphigus were examined. Interferon preparations alpha-IF for nasal administration and IN-1 and IN-2 (or leukinterferon) for injections were used. The results evidence that IF preparations activities depend on the methods of the preparation synthesis and purification. alpha-IF and leukinterferon most effectively enhanced the lymphocyte ability to spontaneous, early, and active rosette formation. IN-1 was found less active and enhanced only the ability to spontaneous E-rosette formation, but had no effect on early active E-RFC subpopulations. IF preparations elevated the counts of E-RFC anf active RFC only if these levels were lowered; if these values were normal the agents had no effect. PMID- 2256372 TI - [Besnier-Boeck-Schaumann sarcoidosis]. PMID- 2256373 TI - [The ultrastructural changes in the clinically unaffected skin of patients with pemphigus vulgaris]. AB - Analysis of the results of light optic, immunofluorescent, and electron microscopic studies of biopsy specimens of intact skin of forearms and of the skin adjacent to lesions in 10 patients with untreated pemphigus vulgaris has lead the authors to a conclusion on the uniform pattern of ultrastructural changes in all sites of the epidermis in pemphigus patients. A combination of the signs of involvement of prickle and basal-cell structures (desmosomes and mitochondria) and of signs of cellular metabolic activation (euchromatism, active status of the nucleolus) anticipate the development of intra- and extracellular changes in pemphigus. PMID- 2256374 TI - [The isolation and characteristics of long-term continuous lymphoid cell lines (IK-10 and IK-12) from patients with mycosis fungoides]. AB - Examinations of 26 cell cultures have detected in two cases continuous IK-10 and IK-12 cell lines from patients with mycosis fungoides. Studies of these cell ultrastructure, carried out by transmission electron microscopy, have shown organoids of all types, that are characteristic of both minor and medium lymphocytes and of lymphoblasts. Markers of T-, B-cells and mononuclears are also detectable in these cell lines. The cells express surface immunoglobulins and interleukin-2 receptors. Noteworthy that association of these cells in a population may be in vitro cultivated for more than 2 years. PMID- 2256375 TI - [The cytoarchitectonics of the epidermis in sarcoidosis of the skin]. AB - Histologic and electron microscopic study of the epidermis in, respectively, 30 and 4 patients with skin sarcoidosis has revealed that atrophy of the epidermis is the most incident condition, whose severity depends on microcirculation disorders that are explained by the location of the epithelioid-cell granulomas relative to skin microcirculatory bed. Moderate atrophy involves the following ultrastructural changes in the keratinocytes: increased count of ribosomes and mitochondria, tonofibril condensation, perinuclear vacuolization, separation of individual cellular contact sites. If atrophy is well manifest, basal keratinocytes grow in size and the nuclei in them are positioned apically. These data suggest that drugs improving the microcirculation be prescribed to such patients in order to obliterate possible cosmetic defects. PMID- 2256376 TI - [The sex hormone content of the peripheral blood in women with gonorrhea and gonorrhea-trichomoniasis infections]. AB - Peripheral blood estradiol, progesterone, testosterone were measured in 100 women with gonorrhea and Gonococcus-Trichomonas infection. Estradiol levels were found reduced in both phases, progesterone level elevated in the follicular and lowered in the lutein phases of the menstrual cycle as against the norm. Elevated testosterone levels were revealed in the peripheral blood of women with gonorrhea, particularly so in chronic gonorrhea and mixed Gonococcus-Trichomonas infection. Therapy did not result in normalization of blood hormone concentrations, this pointing to advisability of including the drugs correcting hormonal disorders into a complex of treatment of such patients. PMID- 2256377 TI - [The dynamics of Treponema-specific blood immunoglobulins in early forms of syphilis]. AB - The study has involved 73 patients with syphilis, 31 female and 42 male ones, aged 18-42. Four of these suffered from primary seronegative, 14 from primary seropositive, 21 from secondary fresh, 22 from secondary recurrent, and 12 from early latent seropositive syphilis. Peripheral blood sera were under study. Treponema-specific antibodies of the IgM and IgG classes were titered by enzyme immunoassay. The detected changes in Treponema-specific immunoglobulinemia are in good correlation with clinical staged pattern of syphilis and antiinfectious immunity status. PMID- 2256378 TI - [The clinical picture and laser photochemotherapy of obliterating xerotic balanoposthitis]. AB - Presents a detailed clinical description of two forms of xerotic obliterating balanoposthitis. Suggests a working classification of the condition, analyzes morphologic findings, proposes a new approach to therapy: laser photochemotherapy. PMID- 2256379 TI - [An immunochemical study of the antigenic profile of cultured strains of Treponema pallidum]. AB - Antigenic profile of T. pallidum culture strains was under study. To prove the presence of 'active' antigenic substances with antibodies in the blood sera of syphilitics, the authors have employed immunization with antigen preparation and reimmunization with antigen precipitate from syphilitics' blood sera. Crossed immunoelectrophoresis has detected up to 25 antigenic components in US-treated culture strains. Five of these contributed to the formation of the specific precipitate from syphilitics' blood sera pool. PMID- 2256380 TI - [A new universal program of postgraduate physician instruction in dermatology and venereology]. AB - The Chair for Dermatology and Venereology at the Central Institute for Advanced Medical Training has developed a new universal programme for advanced training of physicians in this field; this programme is the sole document regulating continuous education of dermatologists and venereologists. It was approved by the Head Administration of Educating Institutions of the USSR Ministry of Health. The programme structure is based on a block system. Of the 8 blocks (courses) one deals with organizational aspects of dermatological and venereological care, five with dermatology, one with syphilis, one with gonorrhea and nongonorrheal diseases. The Programme includes curricula for two cycles of general and eight cycles of topical continuous education, defines the purposes of these cycles, and specifies who should be admitted for these cycles. The Universal Programme may be used parallel with other forms of continuous education (workshops, ten-day courses, etc.) and for individual education. PMID- 2256381 TI - [The psychoemotional aspects of the pathogenesis of androgenetic alopecia in women]. AB - Psychoemotional status of women suffering from androgenetic alopecia was studied by clinico-psychological and clinico-experimental methods. Differences in personality characteristics, depending on the disease severity, length, and pattern, were revealed. These data evidence the significance of personality characteristics in the genesis of androgenetic alopecia. PMID- 2256382 TI - [The antistaphylococcal properties of plant extracts in relation to their prospective use as therapeutic and prophylactic formulations for the skin]. AB - Antistaphylococcal activities of plant extracts (12 water alcohol glycerol, WAG, 6 water alcohol, WA, 8 alcohol glycerol, AG, extracts) towards reference strains and those isolated from patients with pyoinflammatory diseases of the skin were examined by diluting the preparations in solid media. The strains under study were 69 S. aureus, 44 S. epidermidis, and 2 S. saprophyticus ones. Fifteen plant extracts have shown antistaphylococcal activities. The most active were oak bark, sage and St. John's wort grass WAG extracts, horse radish root and leaf AG extracts, celandine grass WA extract; bur marigold and yarrow grass WA extracts were active towards S. aureus. S. aureus strains isolated from patients were found less sensitive to oak bark, German camomile flower WAG and celandine, bur marigold, and brewing waste WA extracts that the reference strains. S. epidermidis strains isolated from patients with acne rash were less sensitive to sweet flag rhizome WAG, celandine and brewing waste WA extracts that the reference strains. These data may be useful when developing compositions including plant extracts for patients with skin diseases. PMID- 2256383 TI - [The treatment of the acute complications of gonococcal infection]. AB - Twenty-eight male and female patients with acute complications of gonorrheal urethritis and endocervicitis (orchiepidydimitis, epidydimitis, prostatitis, prostatovesiculitis, deferentitis, funiculitis; endomyometritis, endometritis, salpingo-oophoritis, salpingitis, oophoritis) were effectively treated with indomethacin and methyluracil. Indomethacin combined with methyluracil promoted a rapid regression of clinical and laboratory signs of gonorrheal complications, cut down the periods of etiological and clinical cure, reduced the number of postgonorrheal inflammatory processes. PMID- 2256384 TI - [Generalized herpes in a pregnant patient]. AB - A clinical description of generalized herpes in a pregnant patient is presented. Virological and serological studies have confirmed the diagnosis. PMID- 2256385 TI - [Herpes zoster in 2 sisters]. AB - Transmission of herpes zoster infection from one sister to the other is described, resultant from close everyday contacts. Clinical manifestations of the disease (severity, dissemination, course and type of involvement) were much more marked in the elder sister, suffering from disseminated Darier's dyskeratosis and marked debility. Herpes was complicated with vasculitis, necrosis, Pseudomonas aeruginosa infection, development of pneumonia and keratitis. Problems of treatment of such patients are discussed. PMID- 2256386 TI - [A combination of systemic scleroderma and chronic myelosis]. PMID- 2256387 TI - [Treatment efficacy in skin basaliomas]. AB - The authors compare the frequencies of recurrences after various methods of basalioma treatment on the basis of the literature data and their own findings with the patients subjected to skin cryodestruction for this condition in 1983 1988. The frequency of recurrences was found to be 2-4 percent and virtually unrelated to the treatment modality employed. Therefore in choosing the treatment strategy, the physician should consider other features of the therapeutic methods. PMID- 2256388 TI - [Oxygen-dependent phagocytosis in patients with tinea pedis during treatment]. AB - Clinico-cytochemical (with the use of NBT test) studies of 27 patients with T. rubrum-induced trichophytosis of the soles has demonstrated a functional imbalance of the peripheral blood phagocytizing cells. Reduced neutrophil activity is associated with a compensatory elevation of mononuclear fungicidal potential. Chlorophyllipt administration corrected the metabolic shifts. PMID- 2256389 TI - [A case of lupus carcinoma]. PMID- 2256390 TI - [Mycetoma of the foot]. AB - A forty-year-old woman suffering from maduromycosis of the right sole is described with a disease history of 17 years. After a contusion and surgery for fibroma she developed an edema on the skin of the right sole, then ulcers with purulent discharge. She was repeatedly treated on an outpatient basis and in hospital by surgeons, phthisiologist, and dermatologist for osteomyelitis, tuberculosis of the bones, and Kaposi's sarcoma without effect. The diagnosis of maduromycosis of the sole was confirmed by laboratory examinations and histologically by detecting Actinomyces elements. Since conservative therapy has proved ineffective, surgical treatment was recommended. PMID- 2256391 TI - [A urethral tip]. AB - The suggested urethral tip is superior to the known tips and attachments. Its design permits enlarging the range of its application, reducing pain sensations, and improving the asepsis; the tip work may be matched with the work of other urologic instruments according to Charriere's scale; it can be used in both children and adults. PMID- 2256392 TI - [A method for finding the minimal treponemicidal concentration of penicillin]. PMID- 2256393 TI - [Organization of the work of epidemiologists in the district epidemiologic health stations of Moscow by the profile principle]. PMID- 2256394 TI - [Current problems in the global elimination of measles]. PMID- 2256395 TI - [Current criteria for the standardization of allergens]. PMID- 2256396 TI - [Electron microscopic study of bacterial development in colonies. The morphology of bacterial colonies]. AB - The morphology of colonies of some pathogenic Gram-negative and Gram-positive bacteria has been studied by scanning and transmitted electron microscopy. The presence of covers on the surface of cells in colonies has been revealed. The examination of colony fragments in ultrathin section has revealed that cells exist in associations and the elements of cell covers are differentiated in the form of fibrillar structures in the intracellular space. This investigation has shown that covers in the colonies of the bacteria under study should be regarded as their morphological feature playing an important role in the development of the infectious process. PMID- 2256397 TI - [Micrococci in the skin microbiocenosis of the breasts. Ecologic characteristics of the colony]. AB - The ecological characteristics of the micrococcal community on the skin of the mammary glands of nulligravidae, pregnant and puerperant women have been studied. The species composition of the community, the population size and occurrence of each species, its participation in the dominant structure of the community have been determined. The comparative evaluation of its types has been made. A decrease in the dominating role of M. luteus in pregnant and puerperant women has been established. The tendency towards the normalization of the structure of the community in the postnatal period has been established. PMID- 2256399 TI - [Model of the spreading dynamics of a hospital infection]. AB - The article deals with the epidemiological model and the corresponding mathematical model of the spread of hospital infection. The mathematical apparatus of Markov's heterogeneous chain is used. The model may be used for the analysis and planning of antiepidemic measures, as well as for the evaluation of their effectiveness. The conditions for the possibility of the application of the newly developed mathematical model have been formulated. The method for calculating the parameters of the model on the basis of data on morbidity in different forms of hospital infection is presented. An example of using the above model for the analysis of the data of observation is considered in detail. PMID- 2256398 TI - [Immunologic monitoring of leptospirosis in the Maritime Territory]. AB - The epidemiological and epizootic situation in Leptospira infections at the Maritime [correction of Primorski] Territory is evaluated on the basis of complex studies carried out in 1984-1989. As revealed in these studies, cases of leptospirosis among humans have a sporadic character and are mainly registered among professional high risk groups of the population. In the immunological structure of persons covered by the survey L. hebdomadis, L. pomona and L. javanica prevail. The anthropourgic foci of leptospirosis caused by L. pomona are of the leading epidemiological importance. Swine serves as the main source of infection in these foci. The study revealed the epidemic danger of the natural foci of leptospirosis caused by L. grippotyphosa and L. javanica in rice fields where the decisive factors of leptospirosis proved to be reed voles and striped field mice serving as reservoirs of this infection, as well as the synanthropic foci of leptospirosis caused by L. hebdomadis with house mice serving as the main carriers. PMID- 2256401 TI - [Influenza epidemics in the USSR and Czechoslovakia in 1979-1984]. AB - In this work materials characterizing the appearance and development of influenza epidemic at the territories of the USSR and the Czech Socialist Republic are presented, the common features and differences of the epidemic process in both countries are recorded. The work shows that in both countries the appearance of this epidemic is caused by the same virus. In most cases the epidemic started earlier and lasted longer in the USSR, but morbidity rate during the epidemic was, on the whole, higher in the Czech Socialist Republic. Similarity in the course of the primary period of the epidemic processes from their appearance to their maximum rise was observed. In both countries the maximum rise of morbidity rate was registered on weeks 3-4 from the beginning of the epidemic. PMID- 2256400 TI - [Tick-borne encephalitis in the Estonian SSR]. AB - The foci of tick-borne encephalitis (TBE) of 2 types, differing in their morbidity rates, the character of their immunological structures, the species composition of carrier mites and their capacity for TBE virus carriership, have been shown to exist in Estonia. TBE morbidity is characterized by 4- to 5-year cycles, the overwhelming majority of TBE cases being registered in the area of the joint habitat of both species of mites. During the epidemic season 2 peaks of morbidity rise are registered, which corresponds to peaks in the number of mites in nature. Different epidemic importance of 2 species of carrier mites in TBE morbidity in Estonia has been shown. PMID- 2256402 TI - [Distemper in a population of the Baikal seal]. PMID- 2256403 TI - [Capsule formation by the causative agent of melioidosis in the body]. PMID- 2256404 TI - [The results of clinical trials and the prospects of using the Soviet preparation of human recombinant interferon alpha-2 (reaferon) in medical practice]. AB - The results of the clinical trials of human recombinant interferon alpha-2 (reaferon) make it possible to come to the conclusion that the preparation is well-tolerated and produces a pronounced therapeutic effect in a number of viral and oncological diseases. The Pharmacological Committee of the USSR has recommended reaferon for use in acute hepatitis B, hairy cell leukemia, renal cancer at stage IV, disseminated sclerosis, ocular herpes. The use of reaferon has been found to be promising in the treatment of papillomatosis of the larynx, Kaposi's sarcoma, mycosis fungoides, chronic myeloleukemia. PMID- 2256405 TI - [The diagnostic effectiveness of an immunoenzyme test system for determining diphtheria toxin antigens in the blood serum in a clinical laboratory trial]. AB - The data on the approbation of the diagnostic value of the enzyme immunoassay (EIA) system for the determination of diphtheria toxin in the blood sera of diphtheria patients and persons suspected for diphtheria are presented. The EIA system was prepared on the basis of F(ab)2 fractions of purified antidiphtheria antibodies. 240 serum samples from diphtheria and tonsillitis patients and from healthy persons were studied. Diphtheria toxin was determined in all patients with the toxic form of diphtheria and in 41.3% of patients with its localized forms. Blood was taken mainly of the first week of the disease. In healthy persons the results of EIA were negative. Thus, the trial of the assay system in a clinical laboratory showed its good diagnostic effectiveness. The use of this EIA system in medical practice is believed to be quite promising. PMID- 2256406 TI - [The immunologic properties of Legionella cytolysin]. AB - Immunogenic properties of cytolysin were studied in experiments on guinea pigs. Preliminary immunization with cytolysin led to the suppression of response to ConA in lymphocytes not adhering to nylon wool and to the stimulation of response to Legionella antigens in lymphocytes adhering to nylon wool. For a month after infection with L. pneumophila the suppression of the proliferative activity of lymphocytes in the spleen of the immunized animals in response to ConA and Legionella antigens was observed, while in the lungs transitory suppression of response to ConA and Legionella antigens was followed by the restoration and then stimulation of proliferation in response to T-cell mitogen and specific antigens. The data obtained in these experiments indicate the capacity of cytolysin for modulating the development of immune response. PMID- 2256407 TI - [The characteristics of the protective and antigenic activities of purified staphylococcal anatoxin in trials with mice of different genotypes]. AB - The protective potency of purified staphylococcal toxoid by the survival rate of immunized mice challenged with the culture of Staphylococcus aureus strain L-1726 and the antigenic properties of the toxoid, determined by the level of antitoxin in the blood of mice and by the intensity of cell-mediated immunity in the spleen cell migration inhibition test, were studied. The experiments were made on CBA and C57BL/6 mice. Purified staphylococcal toxoid was shown to possess antigenic and protective properties in a wide range of doses between 0.15 and 15 binding units per mouse. The protective effect of the toxoid in CBA mice was manifested in the presence of circulating antibodies and cell-mediated reaction or only in the presence of the toxoid. In C57BL/6 mice the protective effect of the toxoid was less pronounced and appeared in combination with the induction of cell mediated immunity in the presence of an extremely low antibody level (0.062 I.U.). PMID- 2256408 TI - [The effect of different Yersinia pestis antigens on the cellular link in immunity]. AB - Immunization with live plague vaccine has been shown to give no protection to thymectomized mice from subcutaneous challenge with Y. pestis virulent strain. Under the action of the vaccine or individual Y. pestis antigens (fraction I) the functional and morphological activation of thymocytes and macrophages is observed, more pronounced in C57BL/6 mice and less pronounced in CBA mice. Y. pestis antigenic preparations (fractions I and II, pesticin) act as T-cell mitogens and are thus capable of inducing the in vitro proliferation of thymocytes. At the same time the in vivo action of fraction II induces a decrease in the level of lymphocytes in the peripheral blood of mice and the destruction of lymphocytes in their thymus and spleen. PMID- 2256409 TI - [Comparative evaluation of efficiency of various immunologic reactions with Candida antigens in detecting immediate hypersensitivity]. AB - In the dynamic survey of 577 persons having had contacts with yeast-like fungi of the genus Candida the effectiveness of tests for the diagnosis of mycogenic sensitization was made with the use of a number of immunological methods. The basophil degranulation test was shown to have higher sensitivity and specificity in the detection of hypersensitivity to microbial strains used in the production processes of microbiological synthesis, while the use of polysaccharide antigens is more expedient in immunological reactions, such as the precipitation test with the finished product obtained by these processes and with C. albicans. Some prevalence of the level of sensitization in the presence of Candida carriership was established in persons having had contacts with these fungi. PMID- 2256410 TI - [The use of monoclonal antibodies with human IgE for determining the level of allergen-specific IgE]. AB - The possibility of using monoclonal antibodies to human IgE, obtained in our laboratory, with the aim to determine allergen-specific IgE in the radioallergosorbent test (RAST), the enzyme immunoassay and the radioimmunoassay has been studied. The results obtained with the use of the standard RAST system (manufactured by Pharmacia, Sweden) and different variants of assay based on the use of our antibodies, labeled with 125I or conjugated with peroxidase, and timothy pollen allergen (obtained from the Stavropol Research Institute for Vaccines and Sera) have been compared. The best results have been obtained with anti-IgE antibodies 11-2, but for working out our assay systems it is necessary to develop our own standards and control limits. PMID- 2256411 TI - [The role of bacteriophages in the self-regulating system of a plague enzootic]. PMID- 2256412 TI - Fine needle aspiration cytologic findings in a case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome). AB - The clinical, fine needle aspiration (FNA) cytologic and histologic findings in a case of sinus histiocytosis with massive lymphadenopathy (SHML) in a five-year old boy are presented. The FNA smears showed a proliferation of plasma cells, lymphoid cells and histiocytes demonstrating emperipolesis that is characteristic of this benign disorder; these cytologic findings were reported as a reactive lymphoid infiltrate with a high content of benign histiocytes. The diagnosis was made on a subsequent open biopsy performed on the persistent lymphadenopathy. The differential diagnosis of lymph nodes containing a prominent component of histiocytes is discussed. PMID- 2256413 TI - Fine needle aspiration cytology and immunocytochemical characterization of the histiocytes in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome). AB - A fine needle aspiration (FNA) biopsy of an enlarged lymph node in a three-year old boy who had asymptomatic cervical and submandibular lymphadenopathy showed large histiocytes with abundant pale, eosinophilic cytoplasm containing well preserved lymphocytes and occasional plasma cells and granulocytes. These features were consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML). Immunophenotypic study of the histiocytes, performed on the FNA smears and on paraffin-embedded sections, showed reactivity for S-100 protein and alpha-1-antichymotrypsin and negativity for lysozyme. These features, which are characteristic of SHML, demonstrate the reliability of FNA cytology in making the diagnosis of this disorder. PMID- 2256414 TI - Immunocytochemistry of fine needle aspirates. A tactical approach. AB - To maximize the potential of immunocytodiagnosis for fine needle aspiration (FNA) samples, it is necessary to be aware of the pitfalls and limitations of these techniques and to formulate a strategy to deal with the many variables involved. Five cases are presented to illustrate some of these variables, which include determining the adequacy of the FNA specimen, selecting tactics for cytologic and immunocytochemical studies, selecting methods for processing the FNA sample, preparing smears to enrich and preserve cells of interest, selecting enzyme labeling methods to optimize sensitivity and specificity, selecting monoclonal antibodies to make the study efficient and pertinent and interpreting the study results. The adequacy of the FNA specimen could be determined by an immediate cytologic assessment of the aspirate as it was obtained. Alcohol-fixed smears and formalin-fixed tissue sections prepared from the aspirate were used for diagnosis; the immunocytochemical studies were used as a diagnostic adjunct for accurate cell identification. Immunocytochemical studies were done on air-dried cytocentrifuge smears of pre-washed cells. While both immunoperoxidase and immunoalkaline phosphatase methods were suitable, we recommend the immunoperoxidase method for the study of aspirates from nonhemopoietic tissues and the immunoalkaline phosphatase method for the study of aspirates with many blood cells present. The proper selection of monoclonal antibodies and the interpretation of the results are best made in the context of the cytologic characteristics of the FNA sample and the clinical features of the patient. PMID- 2256415 TI - Needle tract implantation of papillary carcinoma of the thyroid following aspiration biopsy. AB - A case is reported of a slow-growing papillary carcinoma of the thyroid that caused clinically apparent implantation along the tract of a fine needle aspiration (FNA) biopsy. This appears to be the first report of a cutaneous needle tract metastasis from a papillary thyroid carcinoma. It represents a highly unusual complication of an FNA biopsy of an indolent, slow-growing tumor. PMID- 2256416 TI - Necrosis of a Hurthle cell tumor of the thyroid following fine needle aspiration. Case report and literature review. AB - A Hurthle cell tumor of the thyroid gland resected ten days after fine needle aspiration (FNA) showed extensive necrosis accompanied by a small area of hemorrhage. Although no vascular thrombosis was noted in the histologic specimen, it is possible that the necrosis was the result of compromised vascular supply due to the FNA. PMID- 2256417 TI - Fine needle aspirates of follicular lesions of the thyroid gland. The intermediate-type smear. AB - In order to evaluate fine needle aspirates of thyroid lesions with features intermediate between those of follicular neoplasms and colloid nodules, 38 aspirates in which a definitive diagnosis had not been made were reviewed. On review, ten aspirates were excluded from the "intermediate" category; seven were reclassified as unsatisfactory and one as a cellular colloid nodule. Two papillary carcinomas showed a complex pattern not identified in smears from other lesions; these aspirates were also classified separately for independent evaluation. The remaining 28 aspirates were characterized by syncytial-type tissue fragments with mild nuclear atypia. The association of syncytial-type tissue fragments and orderly sheets and fragments forming a honeycomb pattern in the same aspirate indicated a colloid nodule, though a two-disease process could not be excluded. Of the aspirates containing only syncytial-type tissue fragments, 50% were from adenomas, 25% were from carcinomas, and 25% were from colloid nodules. Criteria to distinguish between the various follicular lesions were not identified in these smears. PMID- 2256418 TI - Fine needle aspiration biopsy of cystic benign lymphoepithelial lesion of the parotid gland in patients at risk for the acquired immune deficiency syndrome. AB - Cystic benign lymphoepithelial lesion (BLL), a previously rare lesion of the parotid gland consisting of marked lymphoid hyperplasia with accompanying squamous-lined cysts, has recently been described in patients with the acquired immune deficiency syndrome (AIDS) or AIDS risk factors. Thirteen fine needle aspiration (FNA) samples of parotid gland masses from patients with AIDS (one case), AIDS risk factors (five cases) or denial of AIDS risk factors (two cases) and a histopathologic diagnosis of BLL were examined. The FNA features that correlated best with the histopathologic findings were (1) a heterogeneous lymphoid population, (2) scattered single and/or clustered foamy macrophages and (3) superficial and/or anucleated squamous cells. Most aspirates showed some combination of these three components. The differential diagnostic considerations, the clinical and radiologic correlations and the relationship of this lesion to HIV infection are discussed. Patients with parotid masses whose aspirates consist of some combination of squamous cells, lymphocytes and foamy macrophages should be questioned for possible AIDS risk factors. PMID- 2256419 TI - Oncocytic nodule. An unusual case of a submaxillary gland mass in an elderly patient. AB - A submaxillary gland mass in an elderly woman was diagnosed as an oncocytic nodule by cutting needle biopsy and was followed with serial fine needle aspiration (FNA) biopsy for seven years. All specimens showed pure populations of oncocytes. Oncocytic nodules of the salivary gland are unusual lesions that may represent hyperplastic proliferations or true neoplasms. Although oncocytic metaplasia is commonly identified in the salivary glands of elderly patients, oncocytes rarely form masses that are targets for needle biopsy. This case suggests that FNA biopsy may be a useful method of evaluating salivary gland lesions in elderly patients who are not candidates for surgery. PMID- 2256420 TI - Extraskeletal myxoid chondrosarcoma with intranuclear vacuoles and microtubular aggregates in the rough endoplasmic reticulum. Report of a case with fine needle aspiration and electron microscopy. AB - The findings of fine needle aspiration biopsy cytology, histology, immunohistochemistry and electron microscopy in an extraskeletal myxoid chondrosarcoma of the soft tissue of the thigh detected in a 65-year-old man are described. In addition to the more usual cytologic findings of chondroblasts and pleomorphic mesenchymal cells, this tumor displayed distinctive intranuclear cytoplasmic inclusions and microtubular aggregates in the rough endoplasmic reticulum. Cytologic study made the diagnosis of malignancy, suggesting a myxoid sarcoma; the precise diagnosis was made by the subsequent studies on the resected tumor and resin-embedded samples of the aspirate. The suitability of aspirated material in the differential diagnosis of myxoid soft tissue tumors is discussed. PMID- 2256421 TI - Fine needle aspiration biopsy diagnosis of giant-cell tumor of bone. An experience with nine cases. AB - The cytologic findings in nine cases of giant-cell tumor (osteoclastoma) of bone diagnosed by fine needle aspiration (FNA) biopsy are described. The aspirates contained a dual population of cells, consisting of mononucleated tumor cells and multinucleated giant cells (osteoclasts). The tumor cells were usually evident in the FNA smears as cohesive perivascular clusters; some were present as sheets or single cells. The most striking feature, which may best suggest the diagnosis of giant-cell tumor in an FNA smear, was the attachment of the osteoclasts to the cohesive groups of tumor cells. Even when the cells were more dissociated, there was a rather regular distribution of the two types of cells. This series further demonstrates that FNA biopsy permits an accurate cytopathologic diagnosis of giant-cell tumor and that its use can clarify the clinical and radiologic impressions of these bony lesions preoperatively. The differential diagnosis between osteoclastoma and other giant-cell containing bone lesions is discussed in detail. PMID- 2256422 TI - Extramedullary hand mirror cells in pathologic conditions of lymphoid tissue. AB - The hand mirror (HM) cell phenomenon, which usually affects pathologic cells of lymphoid tissue in bone marrow, especially in acute lymphoblastic leukemia (ALL), was seen in B-cell lymphoma cells in cerebrospinal fluid (CSF). It was subsequently detected not only in the bone marrow, but also in extramedullary sites of the lymphoma. Subsequent phase-contrast microscopic study of 45 consecutive specimens of CSF revealed lymphoid cells with HM features in a case of ALL (in which HM cells were subsequently found in the bone marrow) and in a case of acute viral meningoencephalitis. These observations demonstrate that the HM cell phenomenon, which is considered to be a cellular alteration resulting from incorporation in the cell of antigen-antibody complexes, is not unique to bone marrow. It can be present in extramedullary sites and can be seen in exfoliated cells in CSF, where its detection is facilitated by the use of phase contrast microscopy. PMID- 2256423 TI - Urothelial cell changes due to busulfan and cyclophosphamide treatment in bone marrow transplantation. AB - Since the administration of cyclophosphamide and busulfan can cause hemorrhagic cystitis and changes in urothelial cells, an investigation was carried out to see whether patients undergoing bone marrow transplantation (BMT) who were treated with these drugs showed such urothelial changes and whether exfoliative urinary cytology can contribute to the early diagnosis and monitoring of such changes. Morphologic and morphometric analyses were performed on cytocentrifuged, Papanicolaou-stained preparations of 700 samples from 107 patients. Various degrees of urothelial cell changes were found in 30.8% of the cases. These changes consisted mainly of a considerable increase in the size of the nucleus and of a cytoplasm that was often bizarrely shaped. Even the structures of the nucleus and the cytoplasm changed. The results of this study showed that exfoliative urinary cytology permits an early diagnosis and monitoring of urothelial cell changes related to the administration of busulfan and cyclophosphamide in connection with BMT. PMID- 2256424 TI - Hepatic and subcutaneous abscesses due to aspergillosis. Initial diagnosis of a case by intraoperative fine needle aspiration cytology. AB - Laparotomy of a 64-year-old woman with bleeding caused by a perforated anastomotic peptic gastric ulcer disclosed a mycotic abscess in the lower surface of the left hepatic lobe covering the ulcer. Fine needle aspiration (FNA) of the abscess produced a clear milky liquid that was positive for Aspergillus fungi by cytology and subsequent microbiologic and cultural studies. Postoperative diffusion of the aspergillosis into the subcutaneous tissue was similarly confirmed by cytology and Sabouraud solid medium culture. This appears to be the first case of disseminated aspergillosis diagnosed by intraoperative FNA cytology; it confirms that FNA cytology is a rapid, sensitive and important tool for the diagnosis of mycotic infections. PMID- 2256425 TI - The 1988 Bethesda System for reporting cervical/vaginal cytologic diagnoses. PMID- 2256426 TI - The cotton-tipped applicator is not adequate for sampling the transformation zone. PMID- 2256427 TI - Nuclear grooves in papillary thyroid carcinoma. PMID- 2256428 TI - Relationship of cytology and histopathology. PMID- 2256429 TI - The value and limitations of aspiration cytology in the diagnosis of primary tumors: the advantage of a fine needle aspiration center. PMID- 2256430 TI - Fine needle sampling without aspiration. PMID- 2256431 TI - An unusual case of actinomycosis diagnosed by fine needle aspiration cytology. PMID- 2256432 TI - Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase. AB - In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256433 TI - Improved sensitivity of serum thyrotropin measurements. Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin. AB - Most serum TSH assays have a working sensitivity (i.e. the lowest TSH value with an inter-assay coefficient of variation below 10%) around 0.15-0.4 mU/l, which also is the critical area for cut off for further thyroid profile testing when serum TSH is used as a "first line test". A new assay (BeriLux hTSH) based on chemiluminescence was evaluated, and demonstrated a theoretical sensitivity (mean + 2 SD of the zero standard) of 0.005 mU/l and a working sensitivity as low as 0.04 mU/l. Reference range was 0.18-2.60 mU/l (N = 33). Sixty-eight percent (13/19) of hyperthyroid patients had serum TSH less than 0.005 mU/l, all had serum TSH less than 0.037 mU/l. We studied two groups of patients with normal free T4 and T3 indices but serum TSH less than 0.15 mU/l as measured by an immunoradiometric assay. Thirty-five percent (7/20) of patients with nontoxic goitre and 5% (1/20) of L-T4 treated patients had serum TSH less than 0.005 mU/l; and in 60% (11/20) and 30% (6/20), respectively, the levels overlapped the total range for hyperthyroidism. Serum levels of sex hormone-binding globulin expressed as percent of the reference median for the relevant sex (SHBG%) were elevated in both groups of patients (p less than 0.01). Approximately 50% of those with serum TSH overlapping the hyperthyroid range had serum SHBG% levels above reference range. In conclusion, this assay seems superior to most previously reported assays concerning working sensitivity, but it still leaves us with a group of clinically euthyroid patients who has unmeasurably low serum TSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256435 TI - Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus. AB - In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P 450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t1/2) and metabolism: the mean antipyrine t1/2 slowed from 4.7 +/- 0.2 (SEM) initially to 7.8 +/- 0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6 +/- 1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus. PMID- 2256434 TI - Thyroid hormone excess stimulates the synthesis of proteoglycan in human skin fibroblasts in culture. AB - We previously demonstrated that proteoglycan accumulated in the affected skin of circumscribed pretibial myxedema of Graves' disease. As an underlying mechanism responsible for the accumulation, we sought to determine whether excess thyroid hormone was partially responsible for the increase in proteoglycan synthesis. Human skin fibroblasts were cultured in Ham's F-10 medium containing 1% Nutridoma with graded doses of T3 (0.184 x 10(-9) to 46 x 10(-9) mol/l) and were labelled with [35S]sulphate and [3H]glucosamine. Proteoglycans were purified by Sephadex G 50, Q-Sepharose chromatography with NaCl-gradient and Sepharose CL-6B chromatography. 35S and 3H incorporated into dermatan sulphate proteoglycan and heparan sulphate proteoglycan and 3H incorporated into hyaluronan were measured. 35S and 3H incorporation into dermatan sulphate proteoglycan was minimum at a T3 concentration of 0.184 x 10(-9) mol/l, and increased with increasing doses of T3 up to 46 x 10(-9) mol/l. 35S and 3H incorporation into heparan sulphate proteoglycan also increased with increasing-doses of T3. 3H incorporation into hyaluronan was not influenced at all by T3. The increased incorporation of 35S into proteoglycan in high-T3 culture reflects the increased synthesis of proteoglycan because 1. the extent of sulphation of disaccharides examined by thin-layer chromatography was not altered by T3; 2. the specific activity of [35S]sulphate was not influenced by T3, and 3. T3 did not decrease the degradation rate of cell-associated proteoglycan. PMID- 2256436 TI - Characterization of the acidic forms of ovine pituitary luteinizing hormone. AB - The naturally occurring acidic forms of ovine pituitary LH were examined by chromatofocusing. Immunoreactive oLH eluted as six variants (elutions pHs of greater than 7.4, 6.83, 6.59, 6.23, 5.5-4.0, and less than 4.0, designated as "basic forms" and variants II-VI, respectively). In rams, the percentage in each variant averaged 46, 9, 28, 10, 5 and 2, respectively, of the total LH recovered. oLH from non-implanted wethers or wethers implanted with dihydrotestosterone, E2 or dihydrotestosterone + E2 eluted as six similar variants but differences were noted in the distribution of oLH among the variants. Compared to rams, pituitary extracts from non-implanted and dihydrotestosterone-implanted wethers contained significantly higher percentages of oLH eluting as basic forms. In contrast, E2- or dihydrotestosterone-implanted wethers exhibited significantly higher percentages of oLH in the acidic variants. Each of these variants was demonstrated to contain biologically active oLH using an in vitro bioassay. Furthermore, the basic forms of oLH were the most abundant biologically active forms present in pituitary extracts. These results suggest that in addition to the seven basic forms of oLH previously described, there are at least five naturally occurring acidic forms of oLH in pituitary extracts which are biologically active, and the distribution of pituitary oLH among its isohormones, including the acidic forms, appears to be modified by steroids. PMID- 2256437 TI - Effect of 2-buten-4-olide, an endogenous suppressant of feeding, on reproductive function in rats. AB - The effects of 2-buten-4-olide, an endogenous feeding suppressant, on the estrous cycle and LH secretion were studied to determine the influence of this compound on reproductive function. Estrous cycling female Wistar rats were treated ip with 2-buten-4-olide (0, 30 or 100 mg.kg-1.day-1) for 2 weeks. Treatment with 100 mg.kg-1.day-1 delayed the estrous cycle. 2-Buten-4-olide increased the pituitary content of LH (1651.3 +/- 164.4 vs 927.7 +/- 65.1 ng/pituitary; p less than 0.01), and decreased the serum LH level compared with the control level in diestrus (0.16 +/- 0.01 vs 0.26 +/- 0.03 microgram/l; p less than 0.05). However, it did not affect the GnRH content of the mediobasal hypothalamus. The direct effects of 2-buten-4-olide on the pituitary response to GnRH was examined by perifusing the pituitary. Medium containing 2-buten-4-olide (10(-4) mol/l) suppressed the pituitary response to GnRH (2 micrograms/l) (percent increase at 50 min after start of GnRH stimulation: 180 +/- 47 vs 406 +/- 66%; p less than 0.05). These findings suggest that 2-buten-4-olide is involved in the regulation of pituitary gonadotropin secretion directly by suppressing the pituitary responsiveness to GnRH, and that 2-buten-4-olide may play an important role in starvation-induced anestrus. PMID- 2256438 TI - A case of slowly progressive aphasia without generalized dementia in a Japanese patient. AB - A Japanese patient with a 4-year history of slowly progressive aphasia without generalized dementia is described. From 1985 on, this 61-yr-old right-handed dentist showed insidiously progressive deterioration in his speech and auditory comprehension, but has no memory disturbance, disorientation of space, time or persons, acalculia or other impairments in his behavior. His personality changes are unremarkable. He still treats patients at his clinic. General physical and neurological examinations were normal. CT and MRI (1.5T) scans showed widening of the left sylvian fissure and lateral ventricle without any vascular lesions. A PET scan demonstrated focal hypometabolism restricted to the left temporal lobe. The clinical course and picture of our patient corresponds, well to those of slowly progressive aphasia without generalized dementia, described by Mesulam. PMID- 2256439 TI - Long-term outcome of TIAs, RINDs and infarctions with minimum residuum. A prospective study in Madrid. AB - A group of patients with transient ischemic attacks (65 cases), reversible ischemic neurologic deficits (37 cases) and infarctions with minimum residuum (41 cases) was included in a prospective follow-up for a mean period of 5.2 years. Most of the patients were treated with acetylsalicylic acid or other antiplatelet agents, or with anticoagulants. Principal complications during follow-up were: cerebral infarction, 15 cases (10.4%); cerebral hematoma, 2 (1.3%); transient ischemic attacks, 17, (11.8%); reversible ischemic neurologic deficits, 9 (6.2%); myocardial infarction, 4 (2.7%); and death, 11 (7.6%). The cumulative incidence for stroke or death was 6.2% for the first year and 14% for the fifth year. There were no significant risk factors for the occurrence of stroke or vascular death on time-related multivariate analysis (Cox). Disabling stroke was less frequent after infarctions with minimum residuum than after transient ischemic attacks or reversible ischemic neurologic deficits. PMID- 2256440 TI - Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH. AB - The relation between angiographically determined cerebral vasospasm following a subarachnoid hemorrhage and regional cerebral blood flow (CBF) was studied in 63 investigations of 45 patients. The CBF was measured using the intra-arterial 133 Xe clearance technique within one hour of angiography. A positive correlation between regional CBF and diameter of major supplying vessel was observed. However, in the 13 cases with focal vasospasm the reduction in CBF was global and not restricted to the area of the spastic vessel. The cerebral oxygen extraction was reduced but independent of the degree of vasospasm, speaking against vasospasm as the cause for the reduction in CBF. The observed association between reduction in CBF and vasospasms could be caused by a common factor responsible for development of both. Thus, it is proposed that the amount of blood escaping at time of aneurysm rupture determines 1) the amount of reduction in cerebral oxygen uptake and thereby the reduction in CBF and 2) the degree of vasospasm. If so a correlation, yet not causal, between reduction in CBF and degree of vasospasm, will be observed. PMID- 2256441 TI - Neuropathy and myopathy in primary Sjogren's syndrome: neurophysiological, immunological and muscle biopsy results. AB - Seventeen consecutive patients with primary Sjogren's syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum-antibodies against PNM; 1 of IgM-, and 1 of IgA-isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease. PMID- 2256442 TI - Immunosuppressive treatment of patients with amyotrophic lateral sclerosis. AB - Documented treatment for amyotrophic lateral sclerosis (ALS) is not available. Several studies have suggested an immunological etiology and an effect on the course of disease, when ALS-patients were treated with immunosuppressants. The aim of the present study was to evaluate the effect of immunosuppressive therapy in ALS-patients comparing the course of disease in treated patients and in historic controls with ALS; 21 patients were included in the study, 17 men and 4 women. Median age at admission was 54 years for men and 61 years for women. 5 had progressive bulbar palsy, 7 both upper and lower motor neuron affections and 9 progressive muscular atrophy. Patients were treated with prednisolone and azathioprine for 1 year and examined regularly; 12 were treated and followed for more than a year. No definite difference between survival in treated patients and their controls was found. PMID- 2256443 TI - Pharmacokinetic comparison of two carbamazepine slow-release formulations. AB - In a single-blind pharmacokinetic study patients being treated with conventional carbamazepine (CBZ) in a t.i.d. regimen were randomly allocated to identical doses of two CBZ slow-release formulations (Trimonil Retard and Tegretol Retard) administered once daily. Statistical analysis involved the following parameters: AUC, Cmin, Cmax and Fluctuation Index (FI). With regard to Cmin and FI statistically significant differences in favour of Tegretol Retard were observed. PMID- 2256444 TI - Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis. AB - Immunoreactive fibronectin (Fn) was quantified in paired cerebrospinal fluid (CSF) and serum samples from patients with bacterial meningitis (n = 46), tick borne encephalitis (TBE) (n = 6), HIV infection (n = 6), Guillain-Barre syndrome (n = 5), carcinomatous meningitis (n = 11), multiple sclerosis (n = 15), disk disease (n = 11), and controls (n = 28). A highly significant elevation of CSF Fn was found in bacterial meningitis, TBE, and carcinomatous meningitis. There were no significant differences in serum Fn between any of the groups. An Fn index to estimate the rate of intrathecal Fn synthesis reached the highest value in bacterial meningitis. Our findings suggest that CSF Fn may be an indicator of adequate host reaction and tissue repair. For diagnostic purposes, the determination of CSF Fn probably does not add much to routine CSF laboratory tests. PMID- 2256445 TI - Lone atrial fibrillation and stroke. AB - We studied 21 consecutive patients from the Lausanne Stroke Registry, who had first-ever ischemic stroke and lone atrial fibrillation, with a standard protocol of investigations including brain CT, and non-invasive cardiac and arterial tests. Rarity of associated risk factors and extracranial; arterial disease, presence of distal intracerebral occlusions on early angiography, and topography of cerebral infarct suggested that cardioembolism was the cause of stroke, though echocardiographic evidence for an atrial thrombus was uncommon. There was no recurrence during a post-stroke 14-day phase, during which anticoagulant and antiaggregant therapies were systematically avoided. Though low, the main risk of stroke recurrence was 0.99 per 100 patient-years during a mean follow-up period of 4.8 years, including a mean duration of anticoagulant therapy of 2.3 years in 18 patients. On the other hand, no death, severe cardiac events, or disabling anticoagulation-related hemorrhages occurred. PMID- 2256447 TI - Delayed brainstem ischemia following rupture of a basilar artery aneurysm and its reversal by nimodipine. AB - A patient with delayed onset of deteriorating consciousness and episodes of opisthotonos, following rupture of an aneurysm of the basilar artery is described. The condition was reversed by intravenous nimodipine and the final outcome was excellent. PMID- 2256446 TI - Plasma exchange in Guillain-Barre syndrome: effect on anti-peripheral nerve myelin antibodies. AB - Increased levels of anti-peripheral nerve myelin (anti-PNM) antibodies were demonstrated by ELISA in serum from 4 of 7 patients with Guillain-Barre syndrome (GBS). Treatment with plasma exchange (PE) was performed and 6 of the 7 patients showed clinical improvement with marked increase in muscular strength. One patient, however, continued to deteriorate during the treatment. No correlation between clinical improvement and levels of anti-PNM antibodies was observed. Whether the antibodies are of pathogenetic importance in GBS is therefore still unknown. PMID- 2256448 TI - Guillain-Barre syndrome after streptokinase therapy. PMID- 2256449 TI - Regional cerebral blood flow in chronic alcoholics measured by single photon emission computerized tomography. AB - Regional cerebral blood flow (CBF) was measured by single photon emission computerized tomography of inhaled 133-Xe in 20 chronic alcoholic men. Mean CBF was 51 ml/(100 g x min) compared with 53 ml/(100 g x min) in 20 normals. Reduced cerebellar blood flow correlated both to structural abnormalities seen on CT scan and to cognitive dysfunction. Slight abnormalities of the regional CBF was observed in the alcoholics. They had a higher incidence of regional low flow areas than a control group. Low flow areas were found in frontal and posterior parts of the brain not only in patients with atrophia, but also in patients without CT abnormalities, suggesting neuronal dysfunction. The occurrence of regional low flow areas was associated with the severity of alcoholism, cerebral atrophy and intellectual impairment. PMID- 2256450 TI - Arachnoid cysts of the middle cranial fossa: a clinical, radiological and follow up study. AB - Twenty-seven patients with CT-scan-diagnosed arachnoid cysts in the middle cranial fossa were studied. Five (18%) presented with progressive symptoms related to raised intracranial pressure which had developed after minor trauma and secondary bleeding, 12 (44%) presented with non-progressive symptoms, and 10 (37%) exhibited neurological syndromes not referable to the cyst. Among those with non-progressive symptoms, epilepsy was the most common presentation (67%). More than 60% of the cysts were small and limited to the anterior temporal region or to the Sylvian fissure, the remaining cysts involved both the anterior temporal region and the Sylvian fissure, and expanded to the adjacent fronto temporal or fronto-parietal regions. The volume measurements of the brain tissue performed on CT scan revealed that between the volume of the two hemispheres there was no significant difference suggesting any evidence of agenesis or hypoplasia of the affected temporal lobe. PMID- 2256451 TI - Is systemic treatment of osteoporosis and mandibular resorption possible? AB - It is argued that mandibular resorption can be considered as osteoporotic in nature. This calls for a systemic approach in its treatment. One aspect mostly neglected is the tendency of bone to bind calcium and phosphate ions. A direct measure for this tendency is the difference in pH between the bone extracellular fluid and blood plasma with octocalcium phosphate. Calculation of these degrees of saturation of about 2000 data of blood plasma compositions given in the literature learned that calcitonin injections, estrogen replacement and magnesium supplementation increase the tendency of bone to bind calcium and phosphate ions and, hence, should be used in the therapy of mandibular resorption and of bone resorption in general. PMID- 2256452 TI - [Essential bone cavity]. PMID- 2256453 TI - Aluminium in tooth pastes and Alzheimer's disease. AB - Epidemiological studies from Norway and England suggest a relation between the frequency of Alzheimer's disease and the concentration of aluminium in the drinking water. Estimates, made in this study, show that the role of aluminium from tooth pastes may be even more important than that from the drinking water. For that reason we determined in samples of tooth pastes taken from the BENELUX market which brands contained aluminium. This appeared to be the case for about 22% of the brands which according to the manufacturers cover about 60% of the market. PMID- 2256454 TI - Maxillo-facial surgery in 1990. PMID- 2256455 TI - [Magnetic resonance imaging (MRI) of cervico-facial tumors]. AB - Magnetic Resonance Imaging (MRI) gives substantial advantages for the study of tumoral extension in the anatomically complex cervico-facial region. The multiplanar approach permits a better analysis of the anatomical relationships of the tumor, including relationships with the vascular structures, without the need for injecting a contrast medium. The method is able to accurately differentiate tissues and is very sensitive for detecting tumoral tissue. Lesions poorly visible with CT, with poor contrast enhancement or lying in a muscular environment, are well demonstrated. Some difficulties remain for obtaining from patient a complete immobility for a long examination. We think MRI gives a substantial benefit for the diagnostic work-up of cervico-facial tumours, and could be the first imaging technique in this area, particularly if further shortening of the examination time is gained with fast imaging methods and if availability of MRI installations is improved. PMID- 2256456 TI - An analysis of the level of dental care in cardiac patients at risk for infective endocarditis. AB - Three hundred and thirty-eight cardiac patients, at risk of infective endocarditis, filled in a questionnaire consisting of a series of questions on their social, educational, familial, professional, medical and dental history and also on their level of dental care. Univariate (chi-square test) and stepwise discriminant analysis were applied to evaluate the factors related to or responsible for the presence or absence of a sufficient level of dental care, defined as at least one dentist visit per year and once daily teeth brushing. An acceptable level of dental care was present in one third of the dentate but almost nonexistent in edentulous patients. Univariate analysis revealed that in dentate patients level of education, knowledge of endocarditis prophylaxis, previous cardiac surgery, time since first heart operation and type of previous operation (artificial valve surgery) were significantly related to the level of dental care. Level of education, knowledge of endocarditis prophylaxis and time since first heart operation were withheld as independent factors by discriminant analysis. A discriminant score was calculated for each patient which permitted classification of the patients in two groups: one with a very high chance for absence of appropriate dental care and one with an equal chance for sufficient or insufficient care. Patients were also classified according to the number of risk factors. An answer to one of the 3 variables, selected by discriminant analysis, unfavorable to the presence of sufficient dental care, was considered a risk factor. Patients with two risk factors had a very high chance for the absence of sufficient dental care; in those with 0 or 1 factor, chances were divided between sufficient and insufficient dental care. PMID- 2256457 TI - [Clinical value of interleukin 1- and interleukin 2-determinations in patients after kidney transplantation]. AB - In a retrospective study of allograft rejections in renal transplant recipients we examined the value of cytokine production monitoring. Interleukin 1 (IL 1) and interleukin 2 (IL 2) activities were determined in supernatants of mitogen stimulated peripheral blood lymphocytes in 8 renal transplant recipients serially for a period up to 60 days after transplantation. LPS-induced IL 1 as well as PHA induced IL 2 production in patients after renal transplantation were significantly decreased in comparison to healthy controls. Seven episodes of cellular rejection were diagnosed in renal allograft recipients during this time, only 4 rejection episodes, however, were associated with a rise in the IL 1 and simultaneous IL 2 production occurred for 2 up to 3 days before the diagnosis of rejection. Moreover there were 12 instances in which an elevation of IL 1 and IL 2 production was found independently from the rejection. In 8 cases the augmentation of IL 1 and IL 2 production could be associated with clinical infections. We conclude from these results that a cytokine monitoring for the diagnosis of allograft rejection does not seem to be useful. PMID- 2256459 TI - Phagocytosis of cadmium microcrystals by human milk macrophages in vitro. AB - Using an in vitro microassay (phagocytosis of cadmium microcrystals saturated with human serum albumin) the phagocytic activity of human milk macrophages and glass-adherent blood leukocytes, obtained from healthy adult women and physiological neonates, was compared. It was established that the early milk contains lower percentage of glass-adherent phagocytes than peripheral blood and, in addition, their phagocytic activity, i.e. the mean number of particles engulfed per cell, was significantly lower as compared to blood leukocytes of adult women and newborns. PMID- 2256458 TI - Cross-reactivity among the pollen proteins of birch and apple trees. AB - In the spring of 1986, the pollen were collected from apple trees in full blossom, and were investigated for their allergenicity. The patients selected for study were subjects with a combined inhalant allergy to birch pollen and an oral allergy to apple fruit. The apple pollen extract yielded about the same percentage of nondialysable substance as obtained from birch pollen. In contrast to the latter, UV-spectroscopy revealed no flavonoids adsorbed to the apple pollen proteins. Patients with a combined allergy to birch pollen and apple fruit showed positive skin reactions to both birch and apple pollen extract. Inhibition of IgE-binding in RAST to birch pollen was observed by apple pollen extract at a 1000-fold lower potency than the homologous birch allergens. Immunoblotting demonstrated IgG-antibodies in birch-allergic sera cross-reactive with apple pollen components. It is concluded that minor allergenic determinants cross reactive with birch pollen epitopes occur not only in the fruit, but also in the pollen of the apple tree. PMID- 2256460 TI - Multireactive human monoclonal antibodies. AB - Human monoclonal antibodies were tested using different immunochemical procedures for their reactivity with various antigens. The great majority of human monoclonal IgM antibodies (15 out of 24) turned out to bind to a whole series of recognized antigens (DNA, keratin, tetanus toxin, ricin etc.). The specificity of these reactions was detected by competitive assays. For some antibodies a simultaneous reaction with two antigens could be demonstrated by capture bridge technique. IgG antibodies also turned out to be multireactive, but not to the same extent (range of antigens much smaller, only 5-6 out of 53). PMID- 2256461 TI - [Modification of immunotherapy with insect venom]. AB - Allergic side effects give rise to a modification of the immunotherapy. Variation of the injection protocol and/or prophylactic application of antihistamines are successful in many patients. Combined active and passive immunotherapy is helpful only in a part of the remaining cases; this therapy is expensive and practicable only in few specialized clinics. Up to date a superior tolerance together with an at least equal efficacy as compared to conventional aqueous extracts has not been demonstrated either for aluminium precipitated or for chemically modified extracts. PMID- 2256462 TI - [Insect sting allergy--indication of desensitization and problems in evaluating the therapy]. AB - The hyposensitization in IgE-mediated insect venom reactions is presently the sole causal method of treatment. In more than 90% it is possible to prevent life threatening anaphylactic reactions after insect stings. Essential, hitherto unresolved or only partly resolved questions include, for instance, objective parameters of success and, in this connection, the necessary duration of therapy. The determination and assessment of the course of specific IgE- and IgG antibodies with the venom skin titration yield, for the single case, no absolutely safe information regarding the therapeutic effect. An alternative is the provocative sting under clinical conditions, the limitation chiefly results from personal and temporal restrictions. PMID- 2256463 TI - Effects of long-term verapamil therapy on serum lipids and other metabolic parameters. AB - Calcium antagonists have been used successfully in the management of hypertension for more than a decade, but less is known about their long-term metabolic effects. To define the impact of one calcium antagonist, verapamil, on serum lipids and other metabolic parameters, we placed 45 hypertensive patients on verapamil monotherapy and followed them for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglyceride levels were not significantly different from baseline, whereas the mean high-density lipoprotein cholesterol value increased significantly from 1.17 +/- 0.41 mmol/L at the initiation of treatment to 1.39 +/- 0.36 mmol/L at 5.3 years (p less than 0.05). Other important biochemical parameters, including serum glucose, potassium and uric acid levels were unaffected by verapamil therapy. No serious side effects or adverse cardiovascular events occurred during verapamil therapy, and there were no study dropouts. It therefore seems likely that this agent will become increasingly useful in the long-term management of essential hypertension. PMID- 2256464 TI - Vascular protection from atherosclerosis: potential of calcium antagonists. AB - Atherosclerosis is the result of complex, interrelated processes, many of which involve calcium. Interventions that interfere with calcium uptake by cells retard lesion development in experimental models of atherosclerosis, underscoring calcium's critical role in atherogenesis. A wide variety of calcium antagonists, including nifedipine, verapamil and diltiazem, have been shown to protect against atherosclerosis in animal models. While these drugs are quite different from each other pharmacologically, they all block intracellular calcium influx. This common property is thus the proposed mechanism for their antiatherosclerotic effects. The effectiveness of the calcium antagonists against the development of atherosclerosis in experimental models may be relevant in the selection of antihypertensive therapy--provided that their protective effects can be demonstrated in future clinical trials as well. PMID- 2256465 TI - In vitro models of anti-atherosclerotic effects of cardiovascular drugs. AB - In studies performed on cells isolated from the subendothelial intimal layer of both normal and atherosclerotic human aortas, cells from atherosclerotic lesions retained atherosclerotic properties while in primary culture, including enhanced proliferative activity and high lipid level. The content and composition of lipids in cultured cells remained unchanged for the first 10 to 12 days in culture and corresponded to the respective indices in freshly isolated cells. When added to an atherosclerotic cell culture, the calcium antagonist verapamil reduced the total intracellular cholesterol level by threefold and inhibited proliferation and collagen synthesis by cultured cells within 48 hours. Of the 12 calcium antagonists tested, verapamil and nifedipine demonstrated the greatest antiatherosclerotic activity. In contrast, nitrates had no effect on atherosclerotic parameters, while beta blockers increased atherosclerotic manifestations of cultured cells. In studies in which plasma was added to cell cultures, 2 to 4 hours after patients received oral nifedipine or verapamil, their plasma prompted antiatherosclerotic responses from cell cultures by reduced intracellular cholesterol and inhibited atherosclerotic cell proliferation. Plasma of patients who received oral propranolol, however, demonstrated atherogenic characteristics. The atherogenic properties of propranolol were inhibited by nitroglycerin and nifedipine. Use of the atherosclerotic cell model allows the examination of the atherogenic and antiatherogenic properties of various drugs, thus possibly optimizing antiatherosclerotic therapy. PMID- 2256466 TI - Anti-atherosclerotic and vasculoprotective actions of calcium antagonists. AB - Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are "pressure-related," such as stroke. However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy. This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties. Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action. Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease. Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies. In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies. Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study. Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease. PMID- 2256467 TI - Atherogenesis, calcium and calcium antagonists. AB - Hypercholesterolemia and arterial hypertension are highly interrelated risk factors of atherosclerosis. Early lesions in nonhuman primates with dietary hypercholesterolemia resemble atherosclerotic lesions demonstrable in the arteries of American children with comparably elevated plasma cholesterol levels. Lesion formation depends upon calcium-regulated cellular processes such as chemotaxis, adhesion, migration, proliferation, lipid uptake and necrosis. Interventions acting on cell calcium uptake including treatment with calcium chelating agents, lanthanum trichloride, and calcium antagonists may retard atherogenesis in fat-fed animals in the absence of hypolipidemic effects. Recent controlled coronary angiographic trials in patients with coronary artery disease suggest that calcium antagonists may retard the progression of coronary atherosclerosis in humans. Large-scale long-term studies are needed to determine the utility of these agents for the treatment of coronary artery disease. PMID- 2256468 TI - Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications. AB - Coronary artery disease (CAD) is the leading cause of death in most developed countries. Therefore, elucidation of risk factors and associated mechanisms for CAD has been a high priority. Data from the Framingham Heart Study and other large-scale epidemiologic studies have identified major risk factors associated with CAD, demonstrating the adverse effects of increased total and low-density lipoprotein cholesterol levels and the protective effect of high-density lipoprotein cholesterol. Other more recent investigations, including the Lipid Research Clinics Trial and the Helsinki Heart Study, have shown that lowering total cholesterol and raising high-density lipoprotein cholesterol significantly reduce the risk for CAD. Because hypertension is also a significant risk factor for CAD, the assumption has been that blood pressure reduction should offer significant benefits in terms of CAD risk. However, despite their antihypertensive efficacy, diuretics and beta blockers have failed to significantly reduce CAD morbidity or mortality. The adverse effects of these antihypertensive agents on lipid profiles, glucose metabolism and other metabolic parameters may account for their disappointing performance in reducing CAD morbidity and mortality. As a result, newer agents such as angiotensin-converting enzyme inhibitors and calcium antagonists that appear to be free of such adverse effects have garnered considerable attention for their potential to reduce CAD risk. PMID- 2256469 TI - Ciclosporin in minimal-change glomerulopathy and in focal segmental glomerular sclerosis. AB - Results of the available literature and preliminary data of an ongoing multicenter, prospective, randomized Italian trial indicate that ciclosporin (CS), at low doses, may maintain remission of the nephrotic syndrome in most steroid-sensitive patients. In steroid-resistant patients CS may cause either complete or partial remission in about 40% of patients with idiopathic nephrotic syndrome. With doses not exceeding 5 mg/kg/day and careful monitoring of renal and liver function, blood pressure and blood levels, severe side effects can be prevented. Although an extensive use of CS in nephrotic syndrome is still premature, cautious trials may be attempted in patients with steroid toxicity and/or devastating nephrotic syndrome. PMID- 2256470 TI - Lipid-lowering agents in proteinuric diseases. AB - Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis. PMID- 2256471 TI - Glomerular polyanion and control of cell function. AB - The glomerular polyanion comprises all anionic sites of glomerular cell surfaces, basement membranes and extracellular matrix. Charged structures may play a critical pathophysiologic role within the glomerular microcirculation, as loss of charges results in altered permselectivity of the filtration barrier and proteinuria. Neutralization of cell surface negative charges of cultured glomerular epithelial and mesangial cells by the polycation poly-L-lysine (PL) is accompanied by increased prostanoid synthesis. Recent studies have shown that PL enhances mesangial cell proliferation in culture. Conversely, the polyanion heparin prevents the effect of PL, and inhibits the growth-stimulatory effect of serum. Thus, our data suggest that the glomerular polyanion, in addition to maintaining the integrity of the filtration barrier, regulates key cell functions such as eicosanoid biosynthesis and proliferation. PMID- 2256472 TI - Proteinuria. Introduction. PMID- 2256473 TI - Hemodynamic effects of glomerular permselectivity. AB - Glomerular capillary hemodynamics influence glomerular permselectivity to macromolecules, and alterations in these factors can evoke proteinuria. Changes in hemodynamic patterns can alter protein flux by changing its diffusion- or concentration-driven movement in the presence of a constant membrane barrier. Alternatively, hemodynamic forces may disrupt, transiently or irreversibly, the permeability characteristics of the capillary barrier. Maneuvers that lower glomerular capillary pressure appear capable of reversing at least in part, these latter permeability defects. Angiotensin II, provoked by higher levels of dietary protein intake, may be a particularly important mediator of proteinuria both through its effects on diffusion-mediated protein leakage and its tendency to provoke permeability defects due to heightening of glomerular capillary hydraulic pressures. PMID- 2256474 TI - Metabolism of albumin and immunoglobulins in the nephrotic syndrome. AB - The nephrotic syndrome is characterized by the increased urinary excretion of albumin and of other serum proteins of intermediate molecular weight accompanied by a decrease in their serum concentration. Albumin synthesis is increased at the level of mRNA synthesis in response to decreased serum oncotic pressure. However, the magnitude of these responses is dependent upon dietary protein and is insufficient to normalize serum albumin. The absolute rate of albumin catabolism is decreased, serving to normalize serum albumin stores, but in contrast to what occurs in other hypoalbuminemic states, the fractional rate of albumin catabolism is increased. This observation is consistent with a hypothesis that increased renal catabolism contributes to total albumin catabolism in nephrosis. Like albumin, IgG is lost in the urine, its serum concentration is decreased, and the fractional rate of its catabolism is increased, suggesting that the kidney contributes to IgG catabolism in the presence of proteinuria. IgG synthesis responds in a variable fashion in the nephrotic syndrome, and may be decreased, thus contributing to its reduced serum concentration. In contrast, the serum concentration of the high-molecular-weight immunoglobulin IgM is increased, as is the serum concentration of a variety of high-molecular-weight liver-derived proteins. It is unknown by what mechanism serum IgM concentration is increased, but this response serves to defend serum protein concentration and oncotic pressure. PMID- 2256475 TI - Mesangial cell-glomerular basement membrane connections counteract glomerular capillary and mesangium expansion. AB - Glomerular capillaries are perfused at a high hydraulic pressure. Since the capillary mesangium interface presents no morphologically apparent pressure barrier, it is suggested that the hydraulic pressure in the mesangium may also be high. This paper analyzes the structures in the glomerular tuft that are capable of counteracting the distending forces exerted on the tuft by the high hydraulic pressure in its center. The skeletal element of the glomerular tuft is the glomerular basement membrane (GBM). The combination of the GBM with the contractile apparatus of mesangial cells represents the main system stabilizing the glomerular tuft. The mesangial cell-GBM connections counteracting the expansion of glomerular capillaries appear less susceptible to injury than those counteracting mesangial expansion. PMID- 2256476 TI - Urinary proteins of tubular origin: basic immunochemical and clinical aspects. AB - A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase. PMID- 2256477 TI - Coagulation factors in nephrotic syndrome. AB - Nephrotic syndrome (NS) is associated with several disorders of hemostasis: thrombocytosis and platelet hyperaggregability; increased plasma levels of factors V and VIII, and of fibrinogen with blood hyperviscosity; decreased plasma levels of natural anticoagulants: free protein S, and antithrombin III compensated by increased levels of alpha 2-macroglobulin; lowered fibrinolytic activity. Intensity of hypercoagulability is related to the degree of hypoalbuminemia; however, the role of hypercoagulability in the increased incidence of thromboembolic events, including renal vein thrombosis, is not proved. Clotting disorders are due to urinary losses of anticoagulants or to increased liver synthesis of procoagulants stimulated by hypoalbuminemia. Moreover, changes in clotting factors levels may be due to intravascular thrombin formation (marked by increased plasma levels of fibrinopeptide A). During active phases of glomerulonephritides (GN) with NS, thrombin formation might in fact arise in glomeruli, following activation of the glomerular hemostasis system. Isolated glomeruli from human crescentic GN, rabbit nephrotoxic GN and rat HgCl2 autoimmune GN produce excessive amounts of procoagulant (tissue factor) activity (PCA). Sequential studies of the self-limited HgCl2 GN showed that glomerular PCA, proteinuria and glomerular fibrin deposits peaked concomitantly at the acme of the disease, suggesting that immunologically mediated glomerular damage had triggered the extrinsic coagulation pathway. PMID- 2256478 TI - Pathogenesis of hyperlipidemia in the nephrotic syndrome. AB - Both increased synthesis and decreased clearance of lipoproteinemia may contribute to the hyperlipoproteinemia which frequently complicates the nephrotic syndrome with increased levels of total and low-density lipo-protein (LDL) cholesterol as the most characteristic abnormality. The hyperlipoproteinemia may also be characterized by elevated levels of triglycerides, increased concentrations of Apo B, Apo C and Apo E and reduced levels of Apo A-I and Apo A II. The increased lipoprotein synthesis occurs in partly undefined mechanisms related to proteinuria, hypoalbuminemia and, possibly, increased availability of mevalonate as a substrate for cholesterol synthesis. Urinary loss of high-density lipoprotein (HDL) components and other liporegulatory factors may contribute to decreased activity of lipolytic enzymes and result in impaired clearance of cholesterol- and triglyceride-rich lipoproteins of lower densities and altered composition of HDL. The variability in these two metabolic abnormalities may account for the corresponding variability in lipoprotein profiles of patients with the nephrotic syndrome. PMID- 2256479 TI - Blood pressure in minimal change and other types of nephrotic syndrome. AB - Blood pressure was evaluated in adult patients (n = 9) and children (n = 57) with nephrotic syndrome and minimal change glomerulonephritis (GN). Prior to steroid treatment in the edematous phase, hypertension was found in 78% of adults (BP greater than or equal to 140/90 mm Hg or antihypertensive treatment other than diuretics) and 95% of children (BP greater than 95 percentile of age). After complete remission, the prevalence of hypertension decreased to 33% in adults and 19% in children. In 21 children with early focal segmental glomerulosclerosis, the prevalence of hypertension (BP greater than 95th percentile) was 91% and 24% after complete remission. In 20 adult patients with membranous GN, the prevalence of hypertension in the edematous phase was 89% and 30% after complete or partial remission. It is concluded that, irrespective of age, hypertension is a common feature of the nephrotic syndrome unrelated to steroid therapy or renal failure. PMID- 2256480 TI - Proteinuria and progression in human glomerular diseases. AB - Proteinuria is characteristic of many glomerular conditions, and often exceeds 2 3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies. PMID- 2256481 TI - Focus on proteinuria. AB - The treatment of glomerular proteinuria may be directed at: (1) control of basic disease processes; (2) interference with mediator systems; (3) modulation of the physiological determinants of glomerular permselectivity. Glucocorticoids and immunosuppressant agents largely exert their putative beneficial effects through actions on basic processes. Agents which affect mediator systems show great promise but the multiplicity of mediators may frustrate therapeutic efforts. Altering the physiologic determinants of proteinuria, as with diet, angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory agents may be quite useful. The antiproteinuric effects of these maneuvers may not only reduce the impact of proteinuria per se but also retard the rate of progression of renal failure which so frequently accompanies many of the states of abnormal glomerular proteinuria. PMID- 2256482 TI - Role of platelet-activating factor in renal immune injury and proteinuria. AB - Platelet-activating factor (PAF) has been implicated as a potential mediator in renal immune injury, but little is known on the mechanisms by which this endogenous phospholipid could contribute to the development of glomerular proteinuria that occurs during immunologically mediated inflammatory reactions. Several experimental models of renal immune injury, including hyperacute kidney allograft rejection, acute serum sickness and nephrotoxic nephritis, and human studies have clearly indicated that renal damage is associated with increased intraglomerular formation of PAF. However, a definitive proof of its pathophysiologic role has been obtained only by pharmacological inhibition of PAF activity at receptor level. In this context we have documented that the PAF receptor antagonist L-652,731 markedly prevented renal function deterioration and development of proteinuria, and reduced glomerular hypercellularity, fibrin deposition in Bowman's space, and tubular cast formation in a rabbit model of nephrotoxic serum nephritis. Concerning the mechanisms by which PAF may induce proteinuria, it has been suggested that PAF increases glomerular permeability to proteins through the release of cationic proteins from platelets and polymorphonuclear neutrophils infiltrating the glomerular tuft, and their deposition in the glomerular capillary wall with loss of fixed anionic charges. We have recently shown that in isolated rat kidney preparations perfused with a cell-free medium, the addition of PAF, but not its vehicle or 2-lyso-PAF, to the perfusate caused a progressive increase in urinary protein excretion. PAF-induced proteinuria was prevented by exposure of isolated kidneys to the PAF receptor antagonist L-652,731.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256483 TI - Prognostic indicators of the resolution of nonimmune hydrops fetalis and survival of the fetus. AB - To delineate any possible prognostic indicators, we reviewed the ultrasonographic and nonmorphometric findings in 19 antenatally diagnosed cases of nonimmune hydrops fetalis in which it was chosen to continue the pregnancy. Thirteen fetuses died and six survived. Of all parameters examined, including associated anomalies, abnormal karyotype, location of serous fluid, anemia, and possible cause of nonimmune hydrops fetalis, the most sensitive prognostic indicator was the real-time-directed M-mode echocardiographic measurement of the biventricular outer dimension in diastole. All fetuses with biventricular outer dimensions greater than 95% died, whereas all but one with normal biventricular outer dimensions had resolution of nonimmune hydrops fetalis and survived. This was highly significant (p less than 0.001) with the predictive value of a normal biventricular outer dimension being 86% and the predictive value of an enlarged biventricular outer dimension being 100%. PMID- 2256484 TI - Variation and correlation in human fetal umbilical Doppler velocities with fetal breathing: evidence of the cardiac-placental connection. AB - Doppler velocity waveforms in the human fetal umbilical vein and artery were analyzed during episodes of fetal breathing. Heart rate, systolic and diastolic velocities were measured from the umbilical artery waveform. Diastolic velocity varied the most with a mean (+/- SD) coefficient of variation of 16.0% +/- 5.0%. The coefficient of variation of systolic velocity was 7.8% +/- 2.4% and of heart rate was 5.0% +/- 1.8%. We also found that umbilical arterial flow was related to umbilical venous flow, implying an interdependence between fetal cardiovascular blood flow and placental blood flow. During breathing, venous flow varies because of changes in intrathoracic pressure in the fetus. This variation in umbilical venous velocity may affect the umbilical arterial diastolic velocity through alterations in placental filling, and may affect the umbilical arterial systolic velocity through alterations in ventricular filling, which by the Frank-Starling mechanism changes stroke volume. The interdependency of umbilical venous and umbilical arterial blood flow velocities must be considered in the interpretation of the significance of umbilical artery Doppler velocity measurements. PMID- 2256485 TI - The course of labor after endurance exercise during pregnancy. AB - This study was designed to test the hypothesis that continuation of a regular running or aerobics program, or both, during the latter half of pregnancy would have a negative effect on the course and outcome of labor. The onset, course, and outcome of labor were independently monitored in 131 well-conditioned recreational athletes who had an uneventful first half of pregnancy. Daily exercise performance was quantitated before conception and throughout pregnancy. Comparisons were made between the 87 women who continued to exercise regularly at or above 50% of their preconceptional level throughout pregnancy and the 44 who discontinued their regular exercise regimen before the end of the first trimester. The incidence of preterm labor was similar in the two groups (9%). Labor began significantly earlier in the exercise group (277 +/- 6 vs 282 +/- 6 days). The women who continued to exercise had a lower incidence of abdominal (6% vs 30%) and vaginal (6% vs 20%) operative delivery, and active labor was shorter (264 +/- 149 vs 382 +/- 275 min) in those who were delivered vaginally. Finally, clinical evidence of acute fetal stress (meconium, fetal heart pattern, and Apgar score) was less frequent in the exercise group (50% vs 26%), although birth weight was reduced (3369 +/- 318 vs 3776 +/- 401 gm). These data negate the initial hypothesis and indicate that, in well-conditioned women who regularly perform aerobics or run, continuation of these exercise regimens has a beneficial effect on the course and outcome of labor. PMID- 2256486 TI - Neonatal morphometrics after endurance exercise during pregnancy. AB - This study was designed to test the hypothesis that continuation of a regular running and/or aerobics program during late pregnancy at or above 50% of preconceptional levels limits fetal growth. Accordingly, detailed neonatal morphometric data were gathered in the offspring of two groups: 77 well conditioned recreational runners and aerobic dancers who were delivered at term after continuing their exercise regimen at or above 50% of the preconceptional level throughout pregnancy and 55 matched controls. Daily exercise performance was quantitated before conception and throughout pregnancy. Significant reductions in birth weight (-310 gm), birth weight percentile (-20), ponderal index (-0.24), its percentile (-30), and the fetoplacental weight ratio (-0.7) were seen in the offspring of the exercise group whereas crown-heel length (51.4 cm) and head circumference (35.0) were similar in the two groups. Reductions in two-site skin-fold thickness (-1.5 mm), skin-fold percentile (-30), calculated percent body fat (-5.0%), and fat mass (-220 gm) in the offspring of the exercise group confirmed the asymmetric pattern of growth restriction and indicated that approximately 70% of the difference in birth weight could be explained by the difference in neonatal fat mass. In runners, the relative level of exercise performance in the last 5 months of pregnancy explained 40% of the variability in birth weight over an 1100 gm birth weight range. We conclude that continuation of a regular aerobic or running program at or above a minimal training level during late pregnancy results in an asymmetric pattern of growth restriction that primarily impacts on neonatal fat mass. PMID- 2256487 TI - Does fasting interval affect the glucose challenge test? AB - The relationship between fasting interval and glucose screening was assessed in a prospective study of 153 non-diabetic pregnant patients undergoing a standard 50g glucose challenge test. An interval of less than 3 hours after the last meal was found to be associated with a significantly greater insulin response as opposed to a fasting interval of more than 3 hours (121.3 pmol/l vs. 83.5 pmol/l, p less than .001) and a greater insulin/glucose index (0.92 vs. 0.66, p less than .001), with no difference in plasma glucose. Overall, obese patients had a higher glucose response than non-obese, but only higher insulin levels (107 pmol/l vs. 69 pmol/l, p less than .001) and insulin/glucose index (0.79 vs. 0.59, p less than .02) when the fasting interval was greater than 3 hours. Our data suggest that the fasting interval can influence insulin response during a glucose challenge test and the aberration in insulin secretion may effect screening results, especially in the high-risk gravida with glucose abnormality. PMID- 2256488 TI - Relationships between glucose levels and insulin secretion during a glucose challenge test. AB - The relationship between glucose and insulin levels was examined in a prospective study of 153 pregnant patients without diabetes who underwent a standard 50 gm glucose challenge test. One hundred eighteen women had normal screening results (glucose level less than 140 mg/dl) and 35 had abnormal screening values but a normal oral glucose tolerance test. Abnormal responders had greater insulin levels (149 vs 82 pmol/L, p less than 0.0001), and a higher insulin/glucose index (0.96 vs. 0.72, p less than 0.007). Patients with glucose levels less than 100 mg/dl had significantly lower insulin/glucose indices. Overall, obese patients had significantly greater glucose and insulin measurements than did nonobese women, but there was no difference within normal and abnormal groups. Glucose levels accounted for 52% of the insulin output and 29% of the insulin/glucose index variance. Neither age, parity, nor obesity contributed significantly to insulin levels in the multiple regression model. Therefore the accepted threshold for glucose screening reflects abnormal insulin output and this aberration may be indicative of the primary defect in gestational diabetes. PMID- 2256490 TI - Response of placental vasculature to high glucose levels in the isolated human placental cotyledon. AB - We report the effect of high glucose infusion on vascular resistance in isolated human placental cotyledons perfused with Krebs-Ringer-bicarbonate solution containing 80 mg/dl (4.4 mmol/L), 160 mg/dl (8.8 mmol/L), or 320 mg/dl (17.6 mmol/L) D-glucose (n = 6). Placental vascular resistance remained constant during 25-minute perfusion periods with 80 mg/dl followed by 160 mg/dl glucose solution. Subsequent perfusion with 320 mg/dl glucose produced a significant increase in placental vascular resistance. Placentas were also studied in which the placental cotyledon was sequentially perfused for 25-minute periods with solutions containing glucose at 80 mg/dl followed immediately by 320 mg/dl (n = 5). Placental vascular resistance remained constant throughout perfusion with 80 mg/dl glucose solution but increased significantly after beginning perfusion with 320 mg/dl glucose. We conclude that the increase in placental vascular resistance appears to be a function of the high glucose level rather than the duration of glucose perfusion. PMID- 2256489 TI - Effect of low-dose oral contraceptives on carbohydrate and lipid metabolism in women with recent gestational diabetes: results of a controlled, randomized, prospective study. AB - Women with recent gestational diabetes mellitus were randomly assigned to one of two low-dose oral contraceptives to evaluate the effect of low-dose oral contraceptives on carbohydrate and lipid metabolism. A cohort of similar women requesting a non-oral-contraceptive method served as controls. The two oral contraceptives studied were ethinyl estradiol (0.035 mg)-norethindrone (0.40 mg) and ethinyl estradiol (0.030 to 0.040 mg)-levonorgestrel (0.050 to 0.125 mg). A 75 gm, 2-hour oral glucose tolerance test and a fasting lipid profile (total cholesterol, triglyceride, high- and low-density lipoprotein cholesterols) were performed at entry, after 3 months, and after 6 to 13 months of treatment. The prevalence of diabetes at 6 to 13 months (27/156 patients) was not significantly different between groups (non-oral-contraceptive group, 17%; ethinyl estradiol norethindrone, 15%; ethinyl estradiol-levonorgestrel, 20%). When examined by prior gestational diabetes mellitus class, diabetes mellitus was present in 7% of prior class A1 and 29% of women with prior class A2 disease (p less than 0.001). Mean cholesterol and low-density lipoprotein cholesterol levels were significantly improved in all three groups at 3 months and at 6 to 13 months, whereas triglycerides remained unchanged. There were no differences in cholesterol, low-density lipoprotein cholesterol, or triglycerides levels between the groups. After 6 to 13 months, there was a significant increase in high density lipoprotein cholesterol in the ethinyl estradiol-norethindrone group compared with the ethinyl estradiol-levonorgestrel and non-oral-contraceptive groups. PMID- 2256491 TI - Insulin-like growth factor II and nonsuppressible insulin-like activity levels in newborns. AB - We measured insulin-like growth factor II and nonsuppressible insulin-like activity levels in the sera of newborn infants with different birth weights and gestational ages to determine the significance of these peptides in fetal growth. Our results obtained by use of one-way analysis of variance showed that the insulin-like growth factor II and nonsuppressible insulin-like activity levels in premature, average-weight-for-gestational-age, large-for-gestational-age, and small-for-gestational-age newborns were significantly different (p less than 0.01). Although levels in the premature neonates were less than the other three groups and large-for-gestational-age neonates had a higher insulin-like growth factor II level than the other three groups, maternal insulin-like growth factor II levels in all groups were similar. These results suggest that insulin-like growth factor II may play a major role in fetal growth. PMID- 2256492 TI - Growth factor activity in the blood of women in whom preeclampsia develops is elevated from early pregnancy. AB - Preeclampsia is a pregnancy-specific disorder of uncertain cause and pathophysiology that appears to be associated with endothelial cell injury. Our current studies demonstrate that a pregnancy growth factor activity is elevated compared with postpartum values in the blood of women with preeclampsia months before the onset of clinical manifestations of toxemia. A cohort of primigravid women was followed throughout pregnancy and multiple serial plasma samples from six women with preeclampsia and six matched normal women were assayed for mitogenic activity. The data indicated that the ratio of predelivery/postdelivery plasma mitogenic activity was greater in women predestined to meet strict criteria for the diagnosis of preeclampsia compared with matched normal primigravid women. Growth factor activity could distinguish women in whom preeclampsia would develop from their normal peers throughout pregnancy, and as early as the first trimester of gestation (p less than 0.05). Similar studies performed with plasma obtained greater than 6 weeks post partum, when the two groups of patients were clinically indistinguishable, revealed no differences in this index of mitogenic activity. Our results indicate that elevated mitogenic activity ratios of prepartum versus postpartum plasma antedate the clinical recognition of preeclampsia, and return to normal with the resolution of the syndrome. PMID- 2256493 TI - The effect of nifedipine therapy on fetal and placental Doppler waveforms in preeclampsia remote from term. AB - Twenty patients with preeclampsia at a gestational age of 26 to 35 weeks were treated with oral nifedipine until delivery. The mean oral daily dose was 45.1 +/ 11 mg/day (range, 40 to 80 mg/day). Fetal aorta, internal carotid artery, umbilical artery, and uteroplacental Doppler flow velocity waveforms were recorded before treatment and then serially. The mean nifedipine concentration at the time of the Doppler studies was 60.3 ng/ml (range, 10 to 90 ng/ml). The use of nifedipine therapy was associated with a significant decrease in both maternal systolic blood pressure (baseline, 154 to 135 mm Hg, p less than 0.001) and diastolic blood pressure (baseline, 100 to 88 mm Hg, p less than 0.001). However, there was no significant difference in the resistance index between baseline and postnifedipine Doppler studies in either the fetal or uteroplacental vessels. The use of oral nifedipine to control blood pressure in preeclampsia does not affect the resistance indices in fetal or uteroplacental vessels as measured by the Doppler technique. PMID- 2256494 TI - Neuroophthalmologic effects of intravenous magnesium sulfate. AB - To test the hypothesis that visual disturbances are more common during intravenous magnesium sulfate administration than at 1 to 4 days after discontinuation of the drug, 13 women underwent bedside neuroophthalmologic examinations during intravenous magnesium sulfate tocolysis at 2.0 to 3.0 gm hr and again at 1 to 4 days after cessation of therapy. Visual symptoms were common during intravenous magnesium sulfate administration. Blurred vision was present in 12 of 13 patients and diplopia was present in 10 of 13 patients. Abnormal findings during neuroophthalmologic examination occurred in all patients during intravenous magnesium sulfate administration. Findings included ptosis, accommodative and convergence insufficiency, and abnormal pupillary responsiveness to light and near. All patients were symptom-free and had normal examinations after magnesium sulfate was discontinued. These findings suggest that visual disturbances with therapeutic magnesium sulfate are common. PMID- 2256495 TI - Low-dose aspirin. II. Relationship of angiotensin II pressor responses, circulating eicosanoids, and pregnancy outcome. AB - Forty pregnant women (28 to 32 weeks' gestation) were given low-dose aspirin therapy (81 mg/day) from the time of enrollment until delivery; circulating eicosanoid levels and angiotensin II pressor responses were measured before and after 1 week of aspirin therapy. Subsequent clinical outcome was correlated with these results. All women had significant reductions in serum and plasma thromboxane B2 levels with aspirin treatment (p less than 0.01). Eleven women who remained sensitive to the pressor effects of angiotensin II (effective pressor dose less than 10 ng/kg/min) after 1 week of low-dose aspirin treatment exhibited significant decreases (p less than 0.05) in plasma 6-keto-prostaglandin F1 alpha (264 +/- 119 vs 161 +/- 31 pg/ml, mean +/- SD) and prostaglandin E2 (476 +/- 174 vs 351 +/- 112 pg/ml) levels. In contrast, patients who were either nonsensitive (refractory) to angiotensin II (n = 18; greater than or equal to 10 ng/kg/min) before aspirin or became nonsensitive after aspirin administration (n = 11) had no change in either plasma 6-keto-prostaglandin F1 alpha or prostaglandin E2 concentrations. The occurrence of pregnancy-induced hypertension was 100% in the women who remained angiotensin II sensitive during aspirin therapy as compared with 36% and 39% in the other two groups (x2 = 16.14; p less than 0.001). Thus during low-dose aspirin therapy a failure to develop refractoriness to infused angiotensin II is associated with a nonselective inhibition of eicosanoids and the almost certain development of pregnancy-induced hypertension. These observations may reflect a basic defect in vascular adaptation to pregnancy. PMID- 2256496 TI - Maternal and uteroplacental hemodynamic effects of chronic captopril in the hypertensive, term-pregnant rat. AB - The chronic effects of captopril on maternal hemodynamics and organ perfusion were investigated in 10 untreated and 10 captopril-treated pregnant spontaneously hypertensive rats by means of the radioactive-labeled microsphere technique. The normal decrease in blood pressure during gestation was prevented by reduction of litter size to two conceptuses on day 7 of gestation. Captopril (approximately 10 mg/kg/day) or drug vehicle (50% ethyl alcohol) was administered intraperitoneally by an osmotic pump from day 7 to 21. At term mean arterial pressure was 23% lower in the captopril-treated group as the result of a 29% decrease in total peripheral resistance without a significant change in cardiac output. The decrease in total peripheral resistance was primarily caused by a decline in splanchnic and skin resistances. Maternal organ and uteroplacental perfusion were not significantly altered. We conclude that administration of captopril during the last 2 weeks of pregnancy in the hypertensive rat effectively lowers maternal blood pressure without adverse effects on organ and uteroplacental perfusion. PMID- 2256497 TI - Induction of labor with pulsatile oxytocin. AB - In a prospective, randomized study, 106 patients underwent induction of labor with either pulsed (every 8 minutes) (n = 50) or continuous (n = 56) intravenous infusion of oxytocin. Maternal characteristics, gestational age at induction, induction-delivery interval, analgesia for labor, cesarean section rates, and newborn characteristics were similar in both groups. The mean +/- SEM total oxytocin administered was significantly less in the pulsed group (3564 +/- 487 mU) than in the continuous group (7684 +/- 844 mU; p less than 0.0001); the average dose of oxytocin administered per minute was significantly lower in the pulsed group (3.9 +/- 0.3 mU/min) than in the continuous group (7.8 +/- 0.4 mU/min; p less than 0.0001); the peak or highest administered dose of oxytocin expressed per minute was also signficantly lower in the pulsed group (9.6 +/- 0.8 mU/min) than in the continuous group (14.1 +/- 0.7 mU/min; p less than 0.0001). These significant differences persisted even when controlled for parity, Bishop's score of the cervix, and number of days induction of labor was carried out. Uterine hyperstimulation occurred infrequently in both groups (3.6% to 4.0%). The pulsed group required a significantly smaller infusion volume (25 +/- 14 ml) than the continuous group (780 +/- 84 ml; p less than 0.0001). Thus pulsatile administration uses significantly less oxytocin and infusion fluid but is as effective and safe as continuous infusion. PMID- 2256498 TI - Inhibition of spontaneous uterine contractions during the last trimester in pregnant baboons by an oxytocin antagonist. AB - The effect of a potent oxytocin antagonist, produced in our laboratories, on spontaneous uterine contractions in the pregnant baboon was examined. Three types of uterine contractions were studied: immediately after operation, during the nocturnal period, and near or at labor. Bolus intravenous injections of oxytocin antagonist were given and uterine activity was examined +/- 1 hour after the injection. The oxytocin antagonist caused a precipitate decrease (approximately 70%) in contractile force (mean amplitude x frequency) in the first 15 minutes after injection (p less than 0.05); this force diminished to approximately 90% at the end of 1 hour for both nocturnal and labor contractions. In contrast, uterine contractions immediately after operation were diminished by only 60% within 60 minutes after the oxytocin antagonist. These results indicate that the oxytocin antagonist is a potent inhibitor and suggest that oxytocin is a primary regulator of spontaneous nocturnal and labor uterine contractions in the pregnant baboon. PMID- 2256499 TI - Evidence of a role for protein kinase C in epidermal growth factor-induced prostaglandin E2 synthesis in amnion cells. AB - Human amnion cells synthesize and release prostaglandin E2 in response to epidermal growth factor. The protein kinase C activator, phorbol 12-myristate, 13 acetate also stimulates amnion cell prostaglandin E2 synthesis. We used a human amnion cell line (WISH) to conduct in vitro experiments to investigate a potential role of protein kinase C in the signal transduction pathway leading to epidermal growth factor-induced prostaglandin E2 production. Pretreatment of cultured amnion cells with a low, nonstimulating dose of phorbol 12-myristate, 13 acetate potentiated the action of epidermal growth factor in causing prostaglandin E2 production as measured by radioimmunoassay. The protein kinase C selective inhibitor staurosporine inhibited epidermal growth factor-induced prostaglandin E2 production, further suggesting a role for protein kinase C in epidermal growth factor action. Experiments were conducted in which amnion cells were rendered protein kinase C-deficient by chronic exposure to phorbol ester, which has been shown to down-regulate the enzyme. In these cells, epidermal growth factor caused prostaglandin E2 synthesis at levels comparable to native (non-protein kinase C-deficient) cells. We conclude that protein kinase C plays a more modulatory than direct role in the epidermal growth factor signal transduction cascade that leads to prostaglandin E2 production by amnion cells. We propose a bifurcating transduction scheme in which, under conditions of protein kinase C inactivation, epidermal growth factor alone causes prostaglandin E2 synthesis. When protein kinase C is activated by as yet unknown endogenous substances, the epidermal growth factor responsiveness of the amnion cells is greatly enhanced. This pathway could have important implications in a feed forward mechanism regulating the level of prostaglandin E2 production during the onset of labor. PMID- 2256500 TI - Lymphokine production during term human pregnancy: differences between peripheral leukocytes and decidual cells. AB - Although the fetus is considered to be an "allograft" there is little information concerning the role of lymphokines in human pregnancy. Lymphokines are polypeptides secreted by stimulated lymphocytes that direct the immune response by enabling immune effector cells to communicate with each other. To characterize lymphokine production during normal human pregnancy, we isolated peripheral leukocytes and decidual lymphocyte-like cells from women undergoing repeat cesarean section at term. After stimulation with mitogen and paternal antigen for 24 hours, culture supernatants were assayed for granulocyte-macrophage colony stimulating factor and interleukin-2 by enzyme-linked immunosorbent assay. There was no difference in the amount of interleukin-2 produced by stimulated peripheral and decidual cells. However, granulocyte-macrophage colony-stimulating factor production by stimulated decidual lymphocyte-like cells was significantly greater than granulocyte-macrophage colony-stimulating factor produced by peripheral lymphocytes. Decidual lymphocyte-like cells produced granulocyte macrophage colony-stimulating factor both spontaneously and after stimulation with mitogen or paternal antigen, whereas peripheral leukocytes did not. This suggests that the decidua constitutes a distinct immunologic microenvironment. PMID- 2256501 TI - The effect of maternal hyperoxia on behavioral activity in growth-retarded human fetuses. AB - Thirteen pregnant women who subsequently were delivered of infants with birth weights less than the 3rd percentile were studied for examination of fetal heart rate and fetal activity patients during maternal administration of oxygen at a concentration of 50% or room air for 2 hours. None of the fetuses was acidotic at birth. Maternal transcutaneous PO2 levels increased from 79 +/- 3 mm Hg to 158 +/ 10 mm Hg for the 2 hours of observation. The results indicated that maternal hyperoxia produced sustained fetal breathing activity that was almost 100% higher than that in room air (analysis of variance, p = 0.024). Gross fetal body movements, fetal heart rate accelerations, and fetal heart rate variability increased significantly with increasing observation time (analysis of variance, p less than 0.01), but were not significantly altered by maternal hyperoxia or room air. We conclude that despite significant change in fetal breathing activity, ultrasonographic observation of fetal behavioral activity during maternal hyperoxia could not be used to differentiate severely growth-retarded from normally grown human fetuses. We speculate that altered fetal heart rate and fetal body movement patterns usually associated with intrauterine growth retardation might be related to altered development of the fetal central nervous system and are not reversible during prolonged maternal administration of oxygen. PMID- 2256502 TI - Observations on the cause of oligohydramnios in prolonged pregnancy. AB - There is increasing evidence that implicates reduced amnionic fluid volume as a major determinant of fetal risk in prolonged pregnancy. We sought to determine whether reduced fetal urine production might be associated with oligohydramnios in pregnancies that reach 42 weeks or more. Ultrasonographic measurements of the fetal bladder were obtained every 2 to 5 minutes for 1 hour in 38 gestations verified to be at least 42 weeks. Oligohydramnios was present in eight of the prolonged pregnancies. Similar measurements were performed in 15 normal pregnancies delivered by elective repeat cesarean section between 38 and 40 weeks' gestation. Hourly fetal urine production rates were calculated with sequential bladder volume measurements. The result of this investigation suggest that diminished fetal urine production is associated with oligohydramnios in prolonged pregnancy. The mechanism by which fetal urine production is reduced in prolonged pregnancy remains unknown. A likely possibility is reduced fetal swallowing because of already diminished amnionic fluid volume, the latter a result of placental senescence. PMID- 2256503 TI - A mechanism leading to reduced lung expansion and lung hypoplasia in fetal sheep during oligohydramnios. AB - Our aim was to determine the mechanism whereby oligohydroamnios causes reduced fetal lung expansion and eventual lung hypoplasia. We studied 20 fetal sheep during 2 to 9 days of oligohydramnios produced by drainage of amniotic and allantoic fluids during the last third of gestation. Oligohydramnios led to a reversible reduction in lung liquid volume of 19.5% within 48 hours. During oligohydramnios tracheal pressure, relative to amniotic pressure, rose by 1.7 mm Hg (p less than 0.001); pressures also tended to rise in the fetal pleural space and abdomen, relative to amniotic pressure, and to fall in the amniotic sac. Pressure increments, relative to amniotic pressure, which normally occur in the fetal trachea, pleural cavity, and abdomen during nonlabor uterine contractions, were significantly increased by 1.9 to 2.5 mm Hg during oligohydramnios. Oligohydramnios increased flexion of the fetal thoracolumbar spine, quantified as a reduction in the ratio of spinal radius of curvature to spine length (0.76 in controls vs 0.40 after oligohydramnios, p less than 0.001). In three sets of twins, only the fetus exposed to oligohydramnios was affected. A similar degree of spinal flexion imposed on normal fetal sheep cadavers increased abdominal (1.6 mm Hg), pleural (1.5 mm Hg), and tracheal (2.0 mm Hg) pressure, and caused a significant reduction in fetal lung expansion. We conclude that oligohydramnios in fetal sheep increases spinal flexion, leading to compression of abdominal contents, upward displacement of the diaphragm, and lung compression, favoring loss of fetal lung liquid. These changes, which are accentuated during nonlabor uterine contractions and are reversible, may lead to pulmonary hypoplasia if prolonged. PMID- 2256504 TI - Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm. AB - New murine monoclonal antibodies to a partially purified CA 125 antigen were developed and identified as M 2 and M 11. With immunohistochemical techniques, these new antibodies and OC 125 antibody were used to search for CA 125 in embryonic tissues and adult apocrine sweat glands and mammary glands. The embryonic skin, the periderm, expressed CA 125 antigen and its adult derivatives, the mammary glands and apocrine sweat glands, expressed CA 125 while in the active state of secretion. In a 6-week-old formalin-fixed and paraffin-embedded ectopic embryo specimen, antibodies M 2 and M 11 recognized CA 125 in the periderm, the notochord, the myocardium, the pericardium, the gastroenteric tract, enteric duct remnants in the umbilical cord (vitelline and allantoic ducts), the mesonephric duct, and the amnion. OC 125 staining of these formalin fixed specimens was either very faint or absent. In a formalin-fixed and paraffin embedded specimen of apocrine sweat glands from the axilla, antibodies M 2 and M 11 detected CA 125 antigen intracellularly in the secretory cells. Again no staining was observed with OC 125 antibody. In a frozen and acetone-fixed specimen of lactating mammary glands, antibodies M 2 and OC 125 detected CA 125 antigen intraductally. Colostrum and milk collected from 25 mothers at various stages post partum had mean CA 125 levels of 34,213 U/ml in colostrum, 1469 U/ml at 3 to 7 days, and 105 U/ml at 5 to 26 weeks. PMID- 2256505 TI - A rabbit model for bacteria-induced preterm pregnancy loss. AB - Bacterial infection has been implicated in premature labor in humans. To elucidate mechanisms and potential intervention strategies, we sought to develop a model of infection-induced pregnancy loss in rabbits. On day 21 (70% of gestation), each uterine horn was inoculated hysteroscopically with 0.2 ml containing saline solution of 10(6) cfu Escherichia coli or Bacteroides bivius or Fusobacterium necrophorum. Fetal viability was assessed. Animals were sacrificed at various times or as delivery occurred. Serum progesterone and amniotic fluid prostaglandins were measured. Cultures and histologic sections were prepared. Compared with the saline solution group, E coli and F. necrophorum-inoculated rabbits were significantly more likely to deliver (16 of 16 and six of seven with mean times of 31.9 +/- 10.7 and 28.3 +/- 11.5 hours, respectively for E. coli and F. necrophorum). Positive amniotic fluid cultures for the E. coli group were found in 11 of 12 (92%) and for the F. necrophorum group in three of three cases (100%). Histologic inflammation was seen heavily in both the E. coli and F. necrophorum groups, whereas it was absent in the saline solution group. Inoculation with B. bivius led to a much lower pregnancy loss rate (eight of 32) and less histologic inflammation despite positive uterine cultures in most animals. This model may provide an opportunity to determine mechanisms of clinical or subclinical intraamniotic infection and to test intervention strategies. PMID- 2256506 TI - In vitro inhibition of esterase activity in amniotic fluid: comparison with bacterial cultures. AB - Assessment of leukocyte esterase activity in amniotic fluid for the rapid and reliable diagnosis of chorioamnionitis has been demonstrated previously. We compared in vitro inhibition of esterase activity in amniotic fluid with bacterial cultures to identify the origins of the specific esterases released by the infecting organisms. One hundred forty-one samples were tested (90 uninfected, 51 infected). Each sample was evaluated for Gram stain, cultures, and an in vitro esterase assay followed by ebelactone inhibition. Forty-two patients had positive amniotic fluid cultures. Ebelactone produced varying degrees of inhibition of esterase activity (range, 20% to 60%) in the uninfected samples and in those infected with gram-negative organisms. There was no inhibition in the samples infected with gram-positive organisms. Thus different groups of bacteria may elicit the production of different and specific esterases in infected amniotic fluid, as shown by the differences in in vitro inhibition. PMID- 2256507 TI - Smoking and the antioxidant ascorbic acid: plasma, leukocyte, and cervicovaginal cell concentrations in normal healthy women. AB - The influence of cigarette smoking on the plasma, leukocyte, and cervicovaginal cell ascorbic acid levels in 46 healthy smokers and healthy nonsmokers was investigated. Coded peripheral venous blood and cervicovaginal lavage specimens obtained after informed consent were analyzed simultaneously for their ascorbic acid content. The findings suggest that smoking affects the levels and distribution of ascorbic acid. In smokers (n = 16), the number of exfoliated cervicovaginal epithelial cells and leukocyte ascorbic acid levels was significantly higher (p less than 0.01, p less than 0.05, respectively) compared with nonsmokers (n = 30). In addition, cervicovaginal cell ascorbic acid, plasma reduced and total ascorbic acid levels were significantly lower (p less than 0.001, p less than 0.01, p less than 0.01, respectively). The exfoliated epithelial cell ascorbic acid levels in nonsmokers was fourfold greater than that of leukocytes. The implications of these findings within the context of free radical-induced cellular pertubations in smokers are discussed. PMID- 2256508 TI - Short-term effects of smoking on the pharmacokinetic profiles of micronized estradiol in postmenopausal women. AB - Because smoking is associated with an increased risk of osteoporosis, yet a decreased risk of endometrial carcinoma, a state of relative hypoestrogenism induced by smoking has been suggested. However, because previous data are unclear and do not reflect current trends in smoking intensity and estrogen prescriptions, we examined the estrogen profiles of postmenopausal women, by smoking status, both before and after oral micronized estradiol. Baseline levels of estrone, estradiol, estrone sulfate, and estrone glucuronide were similar in nonsmokers and smokers, but unbound (non-sex-hormone-binding-globulin--bound) estradiol was significantly lower in smoking women (p less than 0.05) and sex hormone-binding-globulin--binding capacity was higher (p less than 0.001). After 1 or 2 mg of micronized estradiol, estrone and estradiol serum profiles were similar but unbound estradiol was significantly lower in women who were smokers (p less than 0.05). Serum estrone glucuronide rose with treatment but was indistinguishable in nonsmokers and smokers. However, maximum changes in serum estrone sulfate were greater in smokers after administration of estrogen, suggesting a hepatic effect. Urinary estrone glucuronide levels increased after 8 hours of oral estrogen but were similar in nonsmokers and smokers with the two doses. It appears that even moderate smoking, as studied here, induces significant changes in hepatic estrogen metabolism and is best reflected by alterations in serum estrone sulfate and sex-hormone-binding-globulin--binding capacity that result in decreased serum unbound estradiol. However, these changes do not appear to require increasing the estrogen dosage to achieve physiologic levels of estrogen in postmenopausal smokers. PMID- 2256509 TI - Correlation of the testicular determinant factor sequence zinc finger Y with varying gonadal phenotypes in a series of 13 subjects with gonadal dysgenesis due to Y aneuploidy. AB - Deoxyribonucleic acid samples from a series of 13 subjects with 45,X/46,X,altered Y, and varying gonadal phenotypes (streak-streak, n = 9; streak-testis, n = 2; testis-testis, n = 2) were analyzed for the presence of the candidate testicular determinant factor sequence zinc finger Y. The Y-specific probes Y97 mapped to Y centromere, pDP105 A,B mapped to Yp and distal Yq11, respectively, hybridized with the deoxyribonucleic acid from all the 13 study subjects. The same deoxyribonucleic acid samples were analyzed for the presence of the zinc finger Y sequence. Eleven of the 13 subjects were positive for the zinc finger Y sequence. Four zinc finger Y-positive subjects had unilateral (n = 2) or bilateral (n = 2) testicular differentiation. Among the nine subjects with bilateral streak gonads, seven showed the presence of this sequence. The lack of testicular differentiation in the presence of quantitatively normal or almost normal zinc finger Y bands could not be explained by mosaicism alone. Mutations not detectable by analysis with the method of Southern with pDP1007, may occur in the testicular determinant factor gene vitiating testicular development. PMID- 2256510 TI - Isolation and characterization of the gene from a human genome encoding 17 beta estradiol dehydrogenase: a comparison of Jar and BeWo choriocarcinoma cell lines. AB - 17-beta-Estradiol dehydrogenase is required for the enzymatic interconversion of estradiol and its weaker related sex steroid, estrone. We isolated and sequenced a complementary deoxyribonucleic acid clone for 17 beta-estradiol dehydrogenase from the BeWo choriocarcinoma cell line. Comparison of the BeWo complementary deoxyribonucleic acid sequence to a previously derived placental complementary deoxyribonucleic acid sequence yields greater than 98% homology. We also isolated the gene for 17 beta-estradiol dehydrogenase from the Jar human choriocarcinoma cell line and elucidated its primary nucleic acid structure. Significant differences in the Jar-deduced complementary deoxyribonucleic acid sequence clearly differentiate it from both the human placental and BeWo forms of 17 beta estradiol dehydrogenase, indicating the existence of two genes for 17 beta estradiol dehydrogenase in the human genome. Evaluation of 17 beta-estradiol dehydrogenase gene expression in BeWo and Jar cells was compared with expression in luteinized granulosa cells. Messenger ribonucleic acid for human placental 17 beta-estradiol dehydrogenase was identified in all three cell types as a 1.3 kilobase band on Northern blot analysis. A second messenger ribonucleic acid species measuring 2.1 kilobase was abundantly present in the granulosa cells. Whether these two species of messenger ribonucleic acid are involved in the regulation of the estradiol dehydrogenase genes is yet to be determined. PMID- 2256511 TI - Antiprogestin treatment decreases midluteal luteinizing hormone pulse amplitude and primarily exerts a pituitary inhibition. AB - Mifepristone (RU 486), a synthetic steroid with antiprogesterone receptor activity, was given with and without naloxone hydrochloride to six women in the midluteal phase to investigate the role of progesterone in the modulation of endogenous opioid activity and the secretion of luteinizing hormone and cortisol. Subjects were evaluated during four sequential monthly admissions during which multiple blood samples were obtained every 15 minutes for 8 hours. Patients were studied during a baseline cycle, after administration of RU 486 alone (100 mg/day), naloxone with RU 486, and naloxone alone. After administration of RU 486 there was a significant decline in total luteinizing hormone secretion (p less than 0.01) and luteinizing hormone pulse amplitude (p less than 0.05), but compared with baseline there was no significant change in luteinizing hormone pulse frequency. After infusion of naloxone there was a significant increase in mean luteinizing hormone values (p less than 0.05) and luteinizing hormone pulse frequency (p less than 0.01) but no change in pulse amplitude. There was no significant difference in mean luteinizing hormone values or luteinizing hormone pulse amplitude and frequency between administration of RU 486 and naloxone plus RU 486. Administration of naloxone alone, RU 486 alone, and RU 486 plus naloxone caused a significant increase in cortisol as compared with baseline cycles (p less than 0.05). These data further support the notion that progesterone is important in the control of luteinizing hormone secretion and suggest that progesterone may primarily influence luteinizing hormone pulse amplitude and pituitary release of luteinizing hormone during the luteal phase. PMID- 2256512 TI - Luteal insufficiency: correlation between endometrial dating and integrated progesterone output in clomiphene citrate-induced cycles. AB - Midluteal phase endometrium was histologically dated with midcycle luteinizing hormone surge time in 29 cycles from 10 parous women during untreated cycles (control) and treatment with clomiphene citrate 50 mg and 150 mg daily on days 5 through 9. Integrated progesterone output for 7 days after luteinizing hormone surge calculated from the daily plasma progesterone levels was 66.6 +/- 9.8 ng/ml in the control group compared with 117.5 +/- 18.6 ng/ml for clomiphene citrate 50 mg treatment and 152.1 +/- 11 ng/ml for clomiphene citrate 150 mg treatment (p less than or equal to 0.05). Only one cycle (clomiphene citrate 150 mg) had an out-of-phase endometrium and a significantly reduced integrated progesterone output of 28 ng/ml. All other cycles showed synchronous endometrial maturation. We conclude that luteal insufficiency as a result of clomiphene citrate treatment in ovulatory women is infrequent and is more likely to be a result of functional outcome of a relative lack of luteal phase progesterone output. PMID- 2256513 TI - Evidence of heterogeneous mechanisms in lipoprotein lipid alterations in hyperandrogenic women. AB - Fifty-one hyperandrogenic women had their lipoprotein lipid profiles determined. Free and albumin-bound testosterone was associated with triglycerides and with high-density lipoprotein cholesterol independent of fasting insulin levels, percent ideal body weight, and waist/hip ratio. To gain insight into mechanisms of these lipid alterations, the women were subgrouped according to apparent source of androgen excess. Whereas all groups had low levels of high-density lipoprotein-2 cholesterol and high triglyceride concentrations, only in those with high luteinizing hormone-to-follicle-stimulating hormone ratios was free and albumin-bound testosterone associated with triglycerides and high-density lipoprotein cholesterol independent of fasting insulin levels. Relationships between percent ideal body weight and waist/hip ratios, free and albumin-bound testosterone, sex hormone binding globulin, fasting insulin and 2-hour insulin levels and blood pressure are not significant in all subgroups, suggesting differing endocrinological influences and differing mechanisms for lipoprotein lipid alterations. PMID- 2256514 TI - Preembryo biopsy and analysis of blastomeres by in situ hybridization. AB - We developed a method for the biopsy of preimplantation mouse embryos (preembryos) at the four- to eight-cell stage, which uses partial zona pellucida dissection. The preembryos were collected in calcium- and magnesium-free phosphate-buffered saline solution with 0.01% ethylenediaminetetraacetic acid, 0.1 mol/L sucrose, and 4 mg/ml of bovine serum albumin to facilitate removal of blastomeres. This allows entry of a fine micropipette into the perivitelline cavity with subsequent removal of a single blastomere by gentle suction. The majority of embryos (75%) from which biopsy specimens were obtained in this fashion developed to the blastocyst stage. The blastomeres obtained were mainly intact and they were fixed to glass slides. After permeabilization, in situ hybridization was performed with chromosome X- and chromosome 3-specific probes. Human unfertilized eggs and blastomeres from human polyspermic embryos also have been analyzed by in situ hybridization with chromosome specific probes. The combination of nondestructive embryo biopsy and in situ hybridization is a possible approach for preimplantation genetic diagnosis. PMID- 2256515 TI - Factors affecting embryo implantation after human in vitro fertilization: a hypothesis. AB - In the clinical practice of human in vitro fertilization, pregnancy is dependent on embryo implantation. Pregnancy is a function of the number of embryos transferred, with multiple embryos resulting in a higher likelihood of pregnancy. We formulated a mathematic model of embryo implantation. This model describes embryo implantation as dependent on three factors--transfer efficiency, embryo quality, and endometrial receptivity. Application of existing embryo implantation data to this model allows the calculation of the approximate value of each of these factors. On the basis of historic data, data obtained from our in vitro fertilization program, and these theoretic considerations, it is our hypothesis that (1) there is an inherent inefficiency associated with the mechanical transfer of embryos into the uterine cavity, which limits the maximal embryo implantation rate; (2) the quality of embryos produced by controlled ovarian hyperstimulation, follicle aspiration, and in vitro fertilization is very high and approaches that of embryos produced in natural cycles in vivo; and (3) endometrial receptivity is markedly diminished in stimulated cycles and is the current rate-limiting step of pregnancy success of in vitro fertilization. PMID- 2256516 TI - Prediction of residual trophoblastic tissue in first-trimester abortions: the role of transvaginal Doppler ultrasonography. PMID- 2256517 TI - Suprapubic or vaginal procedure. PMID- 2256518 TI - Tubal embryo successfully transferred in utero. PMID- 2256519 TI - Use of midforceps applauded. PMID- 2256520 TI - Findings not new. PMID- 2256521 TI - Pharmacokinetics of oral contraceptive steroids and drug interaction. Introduction. PMID- 2256522 TI - Pharmacokinetics of ethinyl estradiol and mestranol. AB - Pharmacokinetally, a 50 micrograms oral dose of mestranol (which itself is inactive) is bioequivalent to a 35 micrograms dose of ethinyl estradiol. Physiologically, mestranol ranges from 50% to 100% of the activity of ethinyl estradiol, depending on the endpoint chosen. Compounds such as these, which are metabolized with a first-pass effect and are enterohepatically recirculated, demonstrate large interindividual and intraindividual variability in their pharmacokinetics. Thus a given dose of ethinyl estradiol in one person may produce an effect equivalent to a substantially larger (or smaller) dose in another person. This wide variability confounds efforts to establish tight dose response relationships, a point rarely considered in clinical or epidemiologic studies of these compounds. The circulating levels of ethinyl estradiol sulfates may be higher than those of free ethinyl estradiol itself. It has been thought that these sulfates represent a "reservoir" of ethinyl estradiol. Our studies show that this idea is untenable because the half-life of the sulfates is not long enough for such an effect. Differences in the pharmacokinetics of ethinyl estradiol and mestranol have been observed in studies of various populations. The reality of these group differences is affirmed by analyses of urinary metabolite patterns. PMID- 2256523 TI - Factors affecting the enterohepatic circulation of oral contraceptive steroids. AB - Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol. PMID- 2256524 TI - Interactions with oral contraceptives. AB - The interaction of a range of different factors with the pharmacologic activity of oral contraceptives is reviewed. Pharmacokinetic interactions with oral contraceptives may occur (1) during absorption and extrahepatic circulation, (2) by interfering with protein binding, and (3) during hepatic metabolism. The hepatic mixed function oxidase system, which is mainly responsible for the metabolism of oral contraceptives, is affected by several different factors and is easily induced. Nutrition affects the activity of many drugs, but information regarding oral contraceptives is meager. Both pharmacokinetic and pharmacodynamic interactions, which may be synergistic or antagonistic, between the estrogen and gestagen components of oral contraceptives, are important, but there is no correlation between the rate of metabolism of the two components. Evidence suggests that some anticonvulsant, antibiotic, and antibacterial drugs may reduce the efficacy of oral contraceptives. Instances of interactions of other therapeutic agents are reported infrequently. The incidence of serious interactions is low and does not appear to have been reduced with low-dose oral contraceptives, probably because of large intersubject variability in the pharmacokinetics of oral contraceptives. PMID- 2256525 TI - Inhibition of oral contraceptive steroid-metabolizing enzymes by steroids and drugs. AB - The major 17 alpha-ethinyl estradiol 2-hydroxylase is humans is the hepatic enzyme cytochrome P-450 IIIA4 (P-450NF), which is known to be inducible by rifampicin or barbiturates. The literature indicates that 17 beta-estradiol, progesterone, and norgestrel are competitive inhibitors and that primaquine and tolbutamide are rather weak noncompetitive inhibitors. Recent experiments in this laboratory indicate that gestodene is a relatively potent mechanism-based inactivator of cytochrome P-450 IIIA4 in vitro. Inhibition requires incubation with the reduced form of nicotinamide adenine dinucleotide phosphate, is time and concentration dependent, and can be partially blocked by the presence of noninhibitory cytochrome P-450 IIIA4 substrates. The in vitro activation by gestodene provides a possible explanation for the increase in plasma estrogen levels reported in women administered gestodene along with 17 alpha-ethinyl estradiol. PMID- 2256526 TI - Prodrugs: advantage or disadvantage? AB - Our knowledge of the peculiarities of prohormones is rather limited, both pharmacologically and clinically. Generalizations cannot be made except that the lapse of time until peak blood values of the active drug have been reached are always greater after intake of the prodrug than after intake of the drug. This finding is presumably of no clinical importance. If pharmacokinetic differences are limited to the phase of distribution, bioequivalence may be assumed. If, on the other hand, the area under the curve during the elimination phase is smaller for the prodrug than for the drug, the potency of the former should be decreased. A shift in the spectrum of endocrine actions as a result of the biotransformation of the prodrug into the active drug is rather the exception than the rule, and so is a change in side effects. If there are major differences in this respect, metabolic pathways in addition to those leading to the respective active drug must also be taken into consideration. PMID- 2256527 TI - Gastrointestinal disease and oral contraception. AB - Oral contraceptive steroids play a major role in modern family planning. With the present tendency to decrease the doses of both estrogens and progestogens, any factor that reduces the bioavailability of the lower-dose preparations may have an impact on contraceptive protection. Although ethinyl estradiol, the most commonly used oral estrogen, is liable to an enterohepatic circulation as unchanged drug, the commonly used progestogens are not. At present, no convincing evidence exists in the human subject that disruption of the enterohepatic circulation by antibiotics or antacids does reduce contraceptive efficacy of the pill. Oral contraceptive steroids are mainly absorbed from the small bowel, and contraceptive efficacy depends on its absorptive capacity. Enhanced passage of gastrointestinal contents or impaired absorption may thus contribute to contraceptive failures in patients who have chronic inflammatory disease, diarrhea, ileostomy, or jejunoileal bypass. PMID- 2256528 TI - Influence of oral contraceptives on drug therapy. AB - Interferences between drugs and oral contraceptives are considered to alter pharmacokinetics and thus the efficacy of steroidal hormones. It should be noted, however, that steroids can also modify the metabolism and pharmacodynamic effects of various substances. To the present knowledge, phase I (i.e., oxidation, demethylation) and phase II reactions (conjugation) are concerned. Drugs sharing those enzymatic systems with oral contraceptives experience either an increase in bioavailability by inhibition of oxidative metabolism or undergo accelerated elimination by induced conjugation. Such interaction may be of practical interest in subjects who take oral contraceptives and are simultaneously treated with antidepressants, antihypertensives, insulin, synthetic glucocorticoids, theophylline, and caffeine. PMID- 2256529 TI - Oral contraception in disease states. AB - Oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease, ischemic heart attack, or cerebral stroke. Patients requiring long-term anticoagulant treatment can be treated with gonadotropin releasing hormone analogs to prevent ovulation, because ruptured follicles can cause massive intraperitoneal bleeding. Patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery. Migraine and diabetes mellitus are regarded as relative contraindications, depending on the individual situation. Long-term diseases, such as Crohn's disease, epilepsy, and sickle cell anemia, also require individualized consultation. PMID- 2256530 TI - A problem-solving approach to teaching electrochemical driving force to undergraduates. AB - The diversity of students in the typical undergraduate general physiology course demands consideration of several important education objectives: the instructor seeks to provide students with a sound understanding of basic physiological concepts, sharpen their analytical skills, and demonstrate how universal physicochemical laws determine function within living systems. These objectives converge in a problem-solving approach to electrochemical driving force and ion flux across biological membranes. PMID- 2256531 TI - A comparison of interactive videodisc instruction with live animal laboratories. AB - This study compared interactive videodisc-simulated laboratories with two types of traditional labs: a traditional general cardiovascular physiology participation lab and a traditional fibrillation/positive pressure ventilation demonstration lab. The two laboratory sections (a total of 85 first-year veterinary medical students) were divided into 12 lab groups of 3-4 students per lab section. These groups were randomly assigned to either a traditional live animal laboratory or an interactive videodisc-simulated laboratory to compare the effectiveness and efficiency of these methods in teaching physiology. A 22-item, multiple-choice/short answer test was given to all students after the laboratories. In both the participation and the demonstration laboratories, there were no significant differences between group test scores of the interactive videodisc groups and the live animal laboratory groups, but there were differences in time spent by both students and instructors. It was concluded that the interactive videodisc-simulated lab was as effective as the traditional live animal labs and was more time efficient than the traditional participation lab. PMID- 2256532 TI - Membrane potential simulation program for IBM-PC-compatible equipment for physiology and biology students. AB - MEMPOT is an interactive graphic simulation program, written in Turbo C for IBM PC-compatible equipment and designed to teach students in the physiological and biological sciences about the measurement and ion dependence of cell membrane potentials. Different external salt solution values can be chosen and an intracellular electrode can be moved on the screen to impale one of a group of cells and measure resting or action potential responses. A simulated voltage-to frequency audio signal emulates normal experimental audio monitoring of the electrode potential, and a window displays a simulated oscilloscope trace (together with "electrical noise") of the resting or action potential response. The average value of each set of successful impalements is determined for each solution. Once measurements have been made over a suitable range of different solutions, the data can be reentered and plotted graphically on the screen and an interactive approach can be used to determine relative sodium-to-potassium permeabilities at rest or at the action-potential peak. A randomization routine varies permeability ratios within a small range between runs. PMID- 2256533 TI - Hands-on laboratory experience in teaching-learning physiology. AB - Reactivation of several model 5 (vacuum tube) Grass polygraphs for active hands on laboratory experiments by small student groups, in contrast to demonstrations and pretaped illustrations of physiological principles, resulted in remarkable rejuvenation of interest and excitement for learning in premed and introductory science classes at Taylor University. Accurate and perceptive observations were performed on the students themselves, each recording his own electrocardiogram, for example, as well as direct recordings from the pithed frog, the turtle heart, the anesthetized rabbit, and noninvasive recordings from students subjects during exercise. In the latter experiment, sweat recruitment patterns were recorded initially on the lower extremities, followed by successive appearances on thigh and abdomen and with final occurrence on the upper extremities and face. To our knowledge, this is the first report of such recruitment patterns during exercise. Results of actual student participation, with organized group discussions, convince us that laboratory teaching remains the premiere mechanism for teaching and learning organ-system physiology. PMID- 2256534 TI - Lectures in physiology: a three-phase evaluation plan. AB - The initial phase of a voluntarily implemented multiphasic plan for improving faculty lectures was completed in 1988 and reported in 1989 [Am. J. Physiol. 256 (Adv. Physiol. Educ. 1): S3-S8, 1989]. That phase, conducted by a teaching consultant, included analysis of the teaching practices of each of seven faculty members. Following lecture observations, each faculty member received a written critique of his/her teaching, and individual as well as departmental strengths and weaknesses were identified. In the 1989 follow-up phase, faculty reviewed the feedback provided in their critiques and attended a seminar on developing effective lectures. Each faculty member was again observed during the presentation of a lecture; the same observation instrument was used in the follow up phase as was used in the initial phase. A comparative analysis of the 1988 and 1989 teaching behaviors was completed for each faculty member and for the whole department. Results indicate that definitive changes had occurred in teaching methods employed since the initiation of the plan. Additional recommendations were made and specific target areas for ongoing improvement were identified. PMID- 2256535 TI - [Pain after sympathectomy]. AB - Surgical sympathectomies and chemical sympatholyses bring about a true sympathetic deafferentation. This leads to central retrograde degenerescence reactions of the pre-ganglionic neurons, to a reduction of the muscular tone and to a secondary neurovascular disorder at the edge of the sympathetic denervation zone. In a limited number of cases, a radiculalgia-like functional painful syndrome may develop. There are variations in the degree of seriousness and evolution, but the outcome is always spontaneously favourable. Forty seven cases of radiculalgias are reported; the onset is sudden, most often at night, and the untoward effects gradually wear off with the recovery of some degree of peripheral vasomotor tone. Although classical antalgic therapies do not seem to affect the spontaneous evolution of this syndrome, the use of membrane stabilizers such as nifedipine does however induce an immediate functional improvement of the neurovascular disorders. This leads to a dramatic sedation of the pain, provided calcium inhibitors were not administered prior to the sympathectomy. PMID- 2256536 TI - [Pain and arteriopathies of the lower limbs]. AB - Painful extremities are not necessarily a manifestation of disturbed circulation. Pain due to circulatory disorder has characteristic features with clinical evidence of its cause. But there is a tendency to ascribe to circulatory disturbances any pain that cannot easily be ascribed to some other cause. Most pain have specific causes arterial venous, lymphatic or neuropathic. The treatment of the arterial occlusion is most often the first therapeutic time. The treatment of the pain is one important part, avoiding necessarily anxiety. The oral morphinic medications are the first choice at this time. PMID- 2256537 TI - [Diagnosis of vascular acrosyndromes: essential acrocyanosis and erythermalgia]. AB - The diagnosis of acrocyanosis and erythromelalgia is done only on clinical grounds. Acrocyanosis is a benign disorder. Erythromelalgia is a very rare syndrome but can be a clue to the early diagnosis of myeloproliferative disorders. PMID- 2256538 TI - [Intravenous sympatholysis in arterial occlusive diseases and acrosyndromes]. AB - Regional intravenous injection of ismelin is a very common pain treatment in sympathetic reflex dystrophies. In view of the mode of action of ismelin, it would be interesting to use that technique in the symptomatic treatment of chronic obstructive arteriopathies and of Raynaud's phenomenon. Surprisingly, few papers deal with that subject, probably because of fear of aggravating ischemia. However, short-term results are satisfactory in terms of pain relief. Long-term follow-up is unfortunately never mentioned. PMID- 2256539 TI - [Our experience of lumbar chemical sympathectomy in arterial occlusive diseases of the lower limbs]. AB - One hundred and sixty two phenol chemical sympathectomy were achieved from 1982 to 1987. After one month and one year, 92 patients get a lasting improvement. The benefit is better for rest pain relief than for intermittent claudication and skin lesions of legs. Diabetic ischaemic disease increased risk of failure of sympathetic block. Results of chemical sympathectomy are similar to the surgical procedure and the incidence of complications is lower. It is concluded that the neurolytic block will be a satisfying experience in patients with obliterative arterial disease not suitable for vascular surgery. PMID- 2256540 TI - [Thoracic sympathectomy by phenol injection under x-ray computed tomography. Two initial results]. AB - Difficulties in surgical or neurolytic techniques of the sympathetic thoracic chain and the results have been controversial in the upper limbs arteriopathies. A percutaneous technique of neurolytic block under computed tomography in two patients, give evidence of efficacy on pain and skin ulcers. PMID- 2256541 TI - [Vascular acrosyndromes]. PMID- 2256542 TI - Childhood soil ingestion: how much dirt do kids eat? PMID- 2256543 TI - Aerosol photoemission for quantification of polycyclic aromatic hydrocarbons in simple mixtures adsorbed on carbonaceous and sodium chloride aerosols. AB - The photoelectric aerosol sensor was applied as a tool for the in situ and on line detection of surface-enriched polycyclic aromatic hydrocarbons (PAHs). Carbon aerosol and sodium chloride aerosol were coated stepwise with up to four different PAHs or simultaneously with three different PAHs (internally mixed aerosol). The measured photoelectric signal of the internally mixed aerosol was compared with the expected signal, which was calculated from the previous calibration of the sensor. An additivity of the individual contributions of the absorbed PAHs on the sum signal was found. Experiments with photoelectrically inactive paraffin adsorbed on photoelectrically active aerosol particles have demonstrated that only the surface composition contributes to the photoemission signal. PMID- 2256544 TI - Feasibility of using liquid crystals for the development of molecularly selective fiber-optic chemical sensors. AB - A new type of fiber-optic chemical sensor has been developed for the determination and differentiation of geometric isomers. The operation of the sensor is based upon the molecular-geometric-selective absorption of polynuclear aromatic hydrocarbons (PAH) on a liquid crystal. The selective interaction of a PAH with a liquid-crystal substrate causes quenching of the liquid-crystal fluorescence. Detection limits of such a device for PAH compounds approach 10( 10) mol/cm3; the sensor response time is about 2 min. Because the sensor is based upon physical absorption, it is reusable and reversible. PMID- 2256545 TI - Chemiluminescent method for continuous monitoring of nitrous acid in ambient air. AB - A continuous-flow method for measuring atmospheric HNO2 concentration in real time has been developed that uses a chemiluminescent NOx monitor. A Na2CO3 solution strips gaseous HNO2 from the atmosphere by means of pulling an air sample and the solution through a glass coil and mixing continuously with ascorbic acid solution which reduces nitrite to NO. The mixture is led into a gas liquid separating coil consisting of microporous PTFE tubing. The NO evolved from the separating coil is swept out by a stream of clean air and detected with a chemiluminescent NOx monitor. The technique utilizes a dual flow system and dual channel NOx monitor to correct positive interferences from NO2 and peroxyacetyinitrate (PAN). The concentration of HNO2 is determined by difference between the two measurements. Sensitivity of the method is a function of the ratio of sampling flow rate to carrier gas flow rate, which permits readily a highly sensitive measurement. PMID- 2256546 TI - Homogeneous chemiluminescent immunoassay based on complement-mediated hemolysis of red blood cells. AB - A novel method was developed for the homogeneous chemiluminescent immunoassay using complement-mediated hemolysis of sheep red blood cells. The chemiluminescent reaction of luminol and H2O2 was catalyzed by hemoglobins leaked from hemolyzed sheep red blood cells. The chemiluminescence was measured by counting photons. When using nonhemolyzed cells, chemiluminescence was virtually not observed. Only hemoglobin released from the cells was chemiluminescent, so that the extent of hemolysis could be measured without separating hemolyzed and nonhemolyzed cells. The immunoassay was done for the immunoagents: complement, hemolysin (anti-sheep red blood cell antibody), and anti-human albumin antibody. In the assay of complement or anti-human albumin antibody, sheep red blood cells used were bound with hemolysin or human albumin, respectively. The cell was hemolyzed by the action of antigen-antibody binding and subsequent activation of complement. The extent of hemolysis depended on the concentration of the antibody or complement. The calibration curves were obtained by chemiluminometric measurements on the added diluted antibody or complement. The sensitivity was 0.047 CH50 unit/mL for complement and below 1.0 micrograms/mL of anti-human albumin antibody. PMID- 2256547 TI - Complete on-line determination of biopolymer molecular weight via high performance liquid chromatography coupled to low-angle laser light scattering, ultraviolet, and differential refractive index detection. AB - An optically modified high-performance liquid chromatography refractive index detector was developed to allow complete on-line determinations for biopolymer molecular weights. On-line concentration, refractive index, specific refractive index increment (dn/dc2)mu, and Rayleigh factor were determined under flow injection analysis (FIA) and size exclusion chromatography (SEC) conditions using low-angle laser light scattering, ultraviolet, and modified refractive index detection. This instrumental system is capable of determining absolute on-line molecular weights. The error and time requirements involved in conventional methodologies for proteins have been reduced. Sample quantities have been reduced from 150 to 200 mg, in conventional off-line methods, to less than 2 mg for on line FIA and 0.5 mg for on-line SEC, if mass absorptivities (a) are known. Otherwise, the determination of a will be the most sample-demanding step, requiring about 3 mg of the pure protein. On-line measurements of (dn/dc2)mu are in good agreement with traditional off-line values established at Donnan equilibrium (usually within 5%). In addition, this technique provides true injected mass as determined by the UV detector, after chromatographic exposure where losses may occur, which is then used in the calculation of biopolymer molecular weight. PMID- 2256548 TI - Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high-performance liquid chromatographic method using internal surface reversed-phase columns. AB - The Hummel-Dreyer size-exclusion high-performance liquid chromatographic method for the determination of protein binding parameters has been improved and automated by use of an internal surface reversed-phase (ISRP) column (5 cm X 4.6 mm) and a computer-controlled mobile-phase delivery system with low volume syringe mixing. The high-efficiency ISRP columns, which are nonadsorptive and exclusionary to serum proteins but allow partitioning of small molecules with an internal peptide bonded phase, maintain high performance after many injections of human serum albumin (HSA), enable the use of short columns, and provide for the resolution of primary ligand from protein binding displacers. The modified Hummel Dreyer high-performance liquid chromatographic method was demonstrated by the determination of binding parameters for warfarin-HSA in phosphate buffer, which were found to be n1 = 1.0, n2 = 2.1, K1 = 3.30 X 10(5) M-1, and K2 = 2.03 X 10(4) M-1. The necessary sequence of chromatographic experiments was repeated 4 times at 18 separate warfarin mobile phase concentrations. Each automated sequence required 8 h to complete. The parameters were measured with a precision of less than 10% relative standard deviation. PMID- 2256549 TI - Molecular ion imaging and dynamic secondary ion mass spectrometry of organic compounds. AB - An ion microscope equipped with a resistive anode encoder imaging system has been used to acquire molecular secondary ion images, with lateral resolution on the order of 1 microns, from several quaternary ammonium salts, an amino acid, and a polynuclear aromatic hydrocarbon which were deposited onto copper transmission electron microscope grids. All images were generated by using the secondary ion signal of the parent molecular species. The variation of parent and fragment molecular ion signals with primary ion dose indicates that, for many bulk organic compounds, bombardment-induced fragmentation of parent molecules saturates at primary ion doses of (1-8) X 10(14) ions/cm2. Subsequent ion impacts cause little further accumulation of damage in the sample, and intact parent molecular ions are sputtered even after prolonged ion bombardment (i.e. primary ion doses greater than 1 X 10(16) ions/cm2). This saturation process allows molecular images to be obtained at high primary ion doses and allows depth profiles to be obtained from simple molecular solid/metal test structures. PMID- 2256550 TI - Fabrication method to enhance stability of N,N,N',N'-tetracyclohexyl-3 oxapentanediamide calcium microelectrodes. PMID- 2256551 TI - Titanium nitride as a coating for surgical instruments used to collect human tissue for trace metal analysis. AB - When metallic surgical instruments are used to collect human tissue, metal contamination may occur, making accurate ultra-trace metal determinations very difficult. In order to reduce this risk as much as possible, surgical instruments made from a stainless-steel core covered by a film of titanium nitride, a very hard compound with high chemical stability and very good wear resistance, were prepared. The degree of risk from trace metal contamination during sample collection was investigated by neutron activation analysis and a radio-release in vitro serum test. As examples of their application, the titanium nitride coated instruments were used to determine Co, Cr and W in the skin of unexposed subjects and of uraemic patients under regular dialysis treatment. PMID- 2256552 TI - Observations of the use of o-phthalaldehyde condensation for the measurement of histamine. AB - The in vitro study of mast cell degranulation utilises the measurement of histamine as a quantitative marker of this process. Histamine is most commonly assayed, following organic extraction, by condensing it with o-phthalaldehyde (OPT) and thereby obtaining a highly fluorescent adduct. A number of variables that might affect the performance of this assay, including assay conditions, stability and purity, were evaluated during the course of developing this assay for use in our laboratory. We observed the stability of OPT-histamine and found it to be very stable at 0 and 25 degrees C, following acidification. Derivatisation conditions and the purity of the leukocyte histamine extract were also assessed, and indicated that derivatisation at low temperatures slows down decay, providing a greater over-all fluorescence intensity. Extraction procedures are necessary, prior to condensation with OPT, to eliminate both positive and negative interfering substances from leukocyte preparations. PMID- 2256554 TI - Experimental evaluation of commercially available semi-permeable membranes for use with parallel-plate dialysers in flow injection systems. AB - Mass transfer in on-line analytical parallel-plate dialysers was studied in the continuous and flow injection (FI) modes in order to characterise the nature of the dialysis process and its dependence on experimental variables. A number of different semi-permeable membrane surfaces were evaluated in the laminar-flow and plug-flow configurations. The fraction of analyte transferred from the donor to the acceptor stream depends on parameters such as type of membrane used, membrane surface, membrane line-length, membrane porosity, concentration of analyte in the donor stream, the use of concurrent and countercurrent flow between the donor and acceptor streams, and flow-rates of the donor and acceptor streams. The dialysis of calcium and chloride ions, in the absence of protein, was studied with different membrane types and dialysers with different dimensions in continuous flow and FI, and the influence of the above mentioned parameters on the dynamic dialysis process of these ions is described. PMID- 2256553 TI - Liquid chromatographic determination of pentachlorophenol in serum, using pre column phase-transfer catalysed dansylation and post-column photolysis with fluorescence detection. AB - Dansylation of pentachlorophenol was carried out after solid-phase extraction of acidified human serum and desorption with dichloromethane, in a dichloromethane water two-phase system using tetrabutyl-ammonium bromide as the phase-transfer catalyst. Derivatisation was complete within 2 min at room temperature. After evaporation of an aliquot of the organic phase, the residue was dissolved in methanol and injected into a reversed-phase chromatographic system, equipped with a post-column photochemical reactor. In the reactor, dansylated pentachlorophenol is converted into highly fluorescent products. The recovery of the analyte from serum was 85 +/- 4%. Calibration graphs for horse and human serum were linear over two decades, with correlation coefficients ranging from 0.996 to 0.999. The detection limit of pentachlorophenol in horse and human serum was 400 pg ml-1. The reproducibility of the total procedure for a human serum sample containing 4 ng ml-1 was 4.5%. PMID- 2256555 TI - Determination of the protein and free amino acid content in a sample using o phthalaldehyde and N-acetyl-L-cysteine. AB - A spectrophotometric method is proposed for determining the protein content in a sample after total acid hydrolysis. In the procedure, free amino acids are caused to react with o-phthalaldehyde and N-acetyl-L-cysteine at pH 9.5, using isoleucine as the reference compound. Correction factors are used to take into account the differences between the molar absorptivities of the amino acid isoindoles and the recoveries of the amino acids after the hydrolysis treatment. The limit of detection was in the range 40-50 micrograms of protein, and the recoveries were usually 101 +/- 3% with a coefficient of variation lower than 4%. The free amino acid content in a partially hydrolysed protein was also determined. PMID- 2256556 TI - Effect of the reactant mixing sequence on the chymotrypsin inhibition assay. AB - In assaying chymotrypsin inhibition by the soybean Bowman-Birk inhibitor, two sequences of mixing the reactants were tried: adding the substrate last (s-last test) or adding the enzyme last (e-last test). The inhibition values obtained from the s-last test were either equal to or lower than those from the e-last test, depending on the pre-mix pH and pre-incubation time, while the values from the e-last test were independent of these conditions. The differences between the two tests were largest at a pre-mix pH of 4.0 or 8.5 and zero near pH 7.0. Abruptly changing the pre-mix pH from 4.0 to 7.0 brought the values of the two tests closer. These observations suggest a reversible, yet limited, hydrolysis of the inhibitor by the very enzyme it inhibits and indicate the greater reliability of the e-last test over the s-last test, paralleling a similar previous finding on the trypsin inhibition assay. PMID- 2256557 TI - Rapid simple cell suspension enzyme-linked immunosorbent assay to demonstrate and measure antibody binding. AB - A simple cell suspension enzyme-linked immunosorbent assay system, which can be used to test the reactivity of antibodies with cells, is described. Such a system is of particular use with cells that are difficult to fix to microtitre plates or when measuring antigens which are labile to fixation techniques. PMID- 2256558 TI - More options with early treatment. PMID- 2256559 TI - Crib therapy treatment results raise questions. PMID- 2256560 TI - Resting position of tongue important. PMID- 2256561 TI - Myofunctional and dentofacial relationships in second grade children. AB - One hundred and thirty-three second graders in rural public school were assessed on a number of dental, skeletal, and oral muscle function measures. Correlational analyses were conducted in order to determine whether specific myofunctional variables were associated with dentofacial development. Significant relationships were observed between open mouth posture and a narrow maxillary arch and long facial height. Labial and lingual rest and swallow patterns were also related to poor coordination of lip and tongue movements. PMID- 2256562 TI - Serial extraction of first premolars--postretention evaluation of stability and relapse. AB - Case records were evaluated for 30 patients who had undergone serial extraction of deciduous teeth plus first premolars followed by comprehensive orthodontic treatment and retention. Diagnostic records were available for the following stages: pre-extraction, start of active treatment, end of active treatment, and a minimum of 10 years postretention. All cases were treated with standard edgewise mechanics and were judged clinically satisfactory by the end of active treatment. Twenty-two of the 30 cases (73%) demonstrated clinically unsatisfactory mandibular anterior alignment postretention. Intercanine width and arch length decreased in 29 of the 30 cases by the postretention stage. There was no difference between the serial extraction sample and a matched sample extracted and treated after full eruption. PMID- 2256563 TI - Vertical changes in high mandibular plane cases following enucleation of second premolars. AB - The records of 23 patients who underwent mandibular second premolar enucleation in the early mixed dentition were studied. The patients were selected at random from a group which had mandibular plane angles in excess of 38 degrees to SN and had not worn headgear prior to mechanical orthodontic therapy. Pre- and posttreatment measurements were compared to measurements made in an earlier study by Isaacson et al. and a significant decrease in lower anterior face height was found. PMID- 2256565 TI - Orthodontic forces generated by a simulated archwire appliance evaluated by the finite element method. AB - The finite element method has been used to determine the stress distribution generated by the initial placement of a simulated preset bracket-type orthodontic appliance utilizing titanium-nickel alloy archwire. PMID- 2256564 TI - The fracture strength of ceramic brackets: a comparative study. AB - Recent demand for esthetic brackets has led to the development and use of ceramic brackets in orthodontics. The purpose of this study was to compare the fracture strength of different ceramic brackets under different surface conditions and ligation methods using a torsional wire bending force. Five different bracket types (two polycrystalline, two single-crystal, and one metal) were tested using elastic and wire ligation, with half being scratched and the other half remaining unscratched. Results showed a significant difference between bracket types and surface conditions. Non-scratched single-crystal brackets had higher fracture strengths and slightly higher fracture loads than polycrystalline brackets. However, single-crystal brackets were significantly adversely affected by surface damage (scratching), while polycrystalline brackets were not significantly affected by surface damage. The fracture behavior of ceramic brackets followed the Griffith model where fracture strength decreased following surface damage. PMID- 2256566 TI - The effect of long-term deflection on permanent deformation of nickel-titanium archwires. AB - The clinician must now consider the alloy along with cross-sectional shape and size when selecting archwires. The purpose of this study is to quantify permanent deformation after long-term deflection of available nickel-titanium archwires. Nine nickel-titanium, one beta-titanium and one stainless steel archwires, .016 inch round, were deflected into orthodontic brackets of simulated archform. One lateral incisor was positioned to yield a deflection of 5 mm in a lingual direction. After wire deactivation, deformation was measured at 1, 14, and 28 days. Two-way ANOVA and Tukey's critical difference tests were used to determine statistical differences. The nickel-titanium wires exhibited better springback characteristics and less permanent deformation than the stainless steel and TMA wires. Several wires increased deformation as deflection time increased. No clinically significant difference was found between presently available nickel titanium wires in terms of permanent deformation, long- or short-term. PMID- 2256567 TI - Unusual supernumerary teeth. AB - This case report describes the presence of 14 supernumerary teeth. Unique factors include symmetrical involvement in the canine and premolar regions of all four quadrants. The appropriate plan of treatment is left up to the reader. PMID- 2256568 TI - Case report ES. AB - Patients occasionally place limitations on the best of us, forcing major changes in our carefully designed treatment plans. When the following plan of orthodontic treatment was proposed by Dr. Roberto Justus (Mexico City, Mexico), the patient ruled out the use of fixed appliances on her anterior teeth. Out of necessity, an alternative approach to treatment proved effective in the correction of this malocclusion. Records gathered 15 years postretention point to the stability of the resulting treatment. PMID- 2256569 TI - Case report AE. Non-surgical correction of a severe Class II malocclusion (Brodie syndrome) AB - With a great deal of growth and cooperation over a period of 57 months it was possible to correct a severe Class II malocclusion (Brodie Syndrome) without surgical intervention. Initially, occlusal function was provided with a biteplate while the mandibular dentition was expanded. Following extraction of maxillary first and mandibular second premolars a fixed appliance (Edgewise) was used to complete all tooth movement. Through the treatment of this case the importance of function, growth and development was recognized. PMID- 2256570 TI - Case report MM. Surgical-orthodontic correction of bilateral buccal crossbite (Brodie syndrome) AB - A surgical approach to treatment was required for this 35-year-old patient to correct a malocclusion characterized by a bilateral buccal crossbite. Surgical procedures included a LeFort 1 osteotomy to reduce maxillary width and correct the vertical asymmetry. The mandible was lengthened with a bilateral sagittal split osteotomy. Treatment options for the nongrowing patient are limited in the correction of severe skeletal disharmonies. PMID- 2256571 TI - Prevention of food allergy in infancy. PMID- 2256573 TI - Individual patterns of immediate skin reactivity to mold extracts. AB - One hundred atopic patients were skin tested intradermally over a 2-year period with 30 different mold extracts. Subjects were monitored for immediate reactions. Data suggest that to evaluate mold sensitivity in atopic patients one must use multiple mold extracts. PMID- 2256572 TI - Migraines, spontaneous abortions, central nervous system involvement and a positive VDRL in a 36-year-old white female. PMID- 2256574 TI - Rice pollen allergy in Taiwan. AB - A panel of tests including intracutaneous skin testing (ST), radioallergosorbent test (RAST), immunoblotting and allergen-induced lymphoproliferation was done to study rice pollen allergy in asthmatic children and to characterize the allergens. Of the 312 asthmatic patients skin tested, 29 (9.3%) had positive reactions (wheal greater than or equal to 6 mm) to rice pollen extract at a concentration of 10(-5) g/mL and the remaining 283 (90.7%) were negative. While eight (34.8%) of the 23 ST-positive patients were also RAST-positive, RAST was negative in all 34 ST-negative patients and 20 normals. Immunoblotting revealed three major allergens, with molecular weights of 16 kD, 26 kD, and 32 kD, respectively. Interestingly, RAST-positive patients showed IgE responses to most allergens but only a few of them had IgG antibodies, while normal controls had stronger IgG responses to the same allergens, particularly to 32 kD, but none had IgE antibody. The preliminary results of rice pollen protein induced lymphoproliferation were not informative; thus, rice pollen proteins do elicit a specific response in asthmatic children and normals, but its pathogenic role in bronchial asthma needs further study. PMID- 2256575 TI - Effect of sulfurous (thermal) water on T lymphocyte proliferative response. AB - We studied the effect of sulfurous water thermal therapy on the phenotype and the proliferative response of peripheral lymphoid cells from ten subjects affected by chronic upper respiratory disease and from six suffering from articular and periarticular disorders. Sulfurous water (S-H2O) therapy did not modify the phenotype and function of peripheral blood mononuclear cells (PBMC) nor did it modify systemic immunologic reactivity. A different result was obtained by analyzing the response to mitogens of peripheral blood mononuclear cells in cell cultures containing graduated amounts of S-H2O. These "in vitro" studies have shown an important dose-dependent inhibitory effect of S-H2O on mitogen induced T lymphocyte proliferation and on IL2 production. H2S present in S-H2O seems to be the primary component responsible for inhibition. Our results are consistent with a local immunosuppressive role of S-H2O, which may explain part of the observed therapeutic effect of inhalation therapy on upper respiratory allergic disorders. PMID- 2256576 TI - Asthma and pregnancy: responsibility of physicians and patients. AB - The successful management of asthma during pregnancy requires a cooperative approach between the obstetrician, the physician managing the asthma, and the patient. This is emphasized by a case report describing a patient with uncontrolled asthma subsequently managed with appropriate medical and obstetrical care. Concern for maternal and fetal health and reassurance of patients are primary concerns. Guidelines for physicians and patients are outlined as are the safety of drugs and therapy in pregnant patients. Physicians must have knowledge of appropriate use of medications during pregnancy. PMID- 2256577 TI - Plasma immunoreactive leukotriene C4 levels in patients with Kawasaki disease. AB - The incidence of wheezing in Kawasaki disease (KD) has been investigated retrospectively. We measured plasma immunoreactive-leukotriene C4 (i-LTC4) levels of patients with KD. Wheezing was observed in 32 (12.5%) of the 256 patients with KD. Patients who had a prior history of bronchial asthma wheezed more frequently than other patients. During the acute stage of KD, plasma i-LTC4 levels both of wheezing and nonwheezing were significantly higher than those of healthy children. During the convalescent stage, plasma i-LTC4 levels of wheezing cases were higher than those of nonwheezing cases. We speculate that LTC4 contributes to the appearance of inflammatory symptoms during the acute stage of KD. During the convalescent stage when patients were taking aspirin, the presence of wheezing was associated with increased plasma levels of i-LTC4. More attention should be paid to the appearance of wheezing during the course of KD, especially in those cases in which the patient has a prior history of bronchial asthma. PMID- 2256578 TI - Positive Multi-Test reactions do not cause false positive reactions at adjacent sites. AB - To answer the question of whether proximity of Multi-Test skin test sites causes false positive reactions, 50 subjects with prior 4+ skin test responses were retested with antigens and ten additional subjects were tested with histamine (1.8 mg/mL). No positive readings occurred at any of the replicate saline control sites adjacent to 3+ or 4+ allergen sites or to 3+ histamine reactions. PMID- 2256579 TI - Bronchial challenge to house dust can induce immediate bronchoconstriction in allergic asthmatic patients. AB - The goal of the study was to evaluate whether natural exposure to house dust could elicit immediate bronchoconstriction. Two groups of asthmatic patients were studied: 12 asthmatics allergic to house dust mites and seven nonallergic asthmatics. The baseline FEV1 was similar in the two groups. Each subject was challenged through a nasal mask connected to nebulizer filled with house dust. Patients were randomly assigned to inhale dust with high or low Group I allergenic level. All allergic patients had an FEV1 drop larger than 20% of the baseline value. This drop was maximal at the 30th minute after challenge. FEV1 remained unchanged in nonallergic asthmatics. Allergic patients challenged with high Group I allergenic house dust (8.4 micrograms/g) had a mean FEV1 drop larger (P less than .01) than those challenged with the low Group I allergenic house dust (0.66 micrograms/g). Late asthmatic reactions were found in only two patients who were challenged with the high Group I allergenic house dust. These two patients had immediate FEV1 drops greater than 50% of the baseline value. Occurrence of symptoms during the test and the drop in FEV1 were correlated (r = .3; P less than .05). Natural exposure to house dust can induce immediate bronchial in allergic asthmatics in a dose-dependent manner. PMID- 2256580 TI - Relationship between asthma and seasonal allergic rhinitis in schoolchildren. AB - The relationship between sensitization to common allergens and the development of asthma and seasonal allergic rhinitis (SAR) was investigated in a total of 419 schoolchildren in a farming community where allergens of both Dermatophagoides farinae (Df) and orchard grass (OG) pollen predominate. Twelve subjects (2.9%) were found to have asthma and 35 subjects (8.4%) SAR. There was no significant association between occurrences of asthma and SAR. The incidence of asthma correlated with DF-specific IgE levels but not with OG-specific IgE levels, whereas that of SAR correlated with OG-specific IgE levels but not with Df specific IgE levels. No significant correlation was detected between IgE antibody levels against Df and OG. These results suggest that asthma occurs independently of SAR. PMID- 2256581 TI - Bahia grass and Timothy grass did not have a cross reactivity by using a nasal and bronchial challenge. PMID- 2256582 TI - Chemicals and drugs as triggers of food-associated disorder. PMID- 2256583 TI - [Anti-basement-membrane antibody mediated, rapidly progressive, glomerulonephritis. Diagnostic and therapeutic strategy based on a retrospective study of 14 cases]. AB - Fourteen cases of anti-GBM antibody-induced RPGN were evaluated retrospectively in terms of renal function improvement and therapeutic risks. Nine men and 5 women (mean age: 55.3 years) were observed over a 9 year period; in three patients, hemoptysis was associated with renal disease (Goodpasture's syndrome). Most of these patients had received combinations of steroid therapy (ST), immunosuppressive drugs (IS) and plasma exchanges (PE). Age, duration of symptoms prior to diagnosis, initial renal function, therapeutic modalities and complications were assessed according to renal outcome: 9 patients (group A, "non responders") remained on dialysis irrespective of the treatment administered; 5 patients (group B, "responders") recovered renal function. Complications, especially infections, were twice as frequent in group A. Two of the 4 recorded deaths were related to the disease or the treatment. Analysis of clinical and pathological values at the time of entry into the study for both groups indicated that oliguria/anuria, serum creatinine greater than 500 mumol/l and greater than 50% crescents, when associated, were factors predictive of poor renal outcome; in these patients, dialysis may be required except in cases of pulmonary hemorrhage. In all other patients, treatment with ST, IS and PE is recommended. Active hemoptysis necessitates pulse steroids or PE; if absent, further tests (carbon monoxide uptake, bronchoalveolar lavage, lung biopsy) are indicated before use of aggressive therapy. PMID- 2256584 TI - [Treatment of systemic diseases with pulse cyclophosphamide: 15 cases]. AB - Fifteen patients suffering from severe systemic diseases were treated with monthly pulses administration of cyclophosphamide (0.7 g/m2 of body surface): 8 acute systemic lupus erythematosus, 2 Wegener's granulomatous, 1 polyarteritis nodosa, 1 rheumatoid vasculitis, 1 progressive systemic sclerosis, 1 relapsing uveitis and 1 dermatopolymyositis. The indications for cyclophosphamide were: glomerulonephritis (6 cases), resistance to previous treatments (7 cases) and undesirable side effects of corticosteroid therapy (2 cases). After 3 pulses, the disease was controlled in 12 patients (80%) and corticosteroids could be decreased in all 12 cases without an evolutive relapse of the disease. Five patients developed infections (2 septicemia, 1 zona, 1 herpes gingival stomatitis and 1 viral meningitis) which were treated without sequelae. One patient developed cystitis with hematuria after the 3rd pulse; association of mesna, a urinary tract protective agent, enabled the continuation of treatment without a cystitis relapse. At the end of our retrospective study, the efficacy of pulse cyclophosphamide administration seems to be satisfactory but the risk of undesirable side effects should limit its use to severe systemic diseases or those resistant to conventional therapies. PMID- 2256585 TI - Subacute cutaneous lupus erythematosus in Greece. A clinical, serological and genetic study. AB - We present herein clinical, serological and genetic findings on 27 Greek, subacute cutaneous lupus erythematosus (SCLE) patients. Twenty-three (85 p. 100) presented with a psoriasifom rash in a photosensitive distribution. Two patients (7.5 p. 100) had an annular rash in a polycyclic pattern. Two other patients exhibited both types of lesions. The majority of our patients also had other skin manifestations, including butterfly rash, discoid lesions and maculopapular rash. Systemic manifestations were: arthralgias or arthritis in 50 p. 100, low grade fever in 35 p. 100, central nervous system involvement in 15 p. 100, Sjogren's syndrome in 18 p. 100 and serositis in 8 p. 100. Anti-nuclear antibodies were found in 93 p. 100; antibodies to Ro (SSA) and/or La (SSB) in 70 p. 100. Twenty one (78 p. 100) satisfied the ARA criteria for systemic lupus erythematosus (SLE). No HLA-DR3 antigen association was found in the 16 patients tested. These findings are somewhat different from those reported previously: a) the frequency of the psoriasiform rash rather than the annular one is the highest in Greek SCLE patients; b) most patients also have other skin manifestations mimicking the full spectrum of SLE with prominent cutaneous lesions; and c) no HLA-DR3 antigen association was found in Greek patients. Environmental, ethnic or genetic factors may be responsible for these differences. PMID- 2256586 TI - [Polymyalgia induced by topical minoxidil]. AB - Topical minoxidil, used in the treatment of baldness, has been commercially available since 1987. Its systemic side effects are rare. We observed an as yet unreported "polymyalgia syndrome" in four otherwise healthy males whose sole medication was topically applied minoxidil. They experienced fatigue, weight loss and severe pain in the shoulders and pelvic girdle, suggesting connective tissue disease. Three patients had a transient rise in liver enzymes, while other laboratory analyses remained normal. Tritanomaly was detected in two patients who underwent systematic color vision testing. All symptoms disappeared after withdrawal of minoxidil. Rechallenge was positive once in one patient and twice in another. The mechanism of this side effect remains to be determined. PMID- 2256587 TI - [Acute drug poisoning in suicidal elderly patients 70 years' old and over. 92 cases in a medical ICU]. AB - Self-inflicted acute drug overdose in suicidal elderly patients appears to be a growing challenge to public health. To the best of our knowledge, little has been published on this topic. Thus we undertook a retrospective study, from January 1969 to October 1989, in a medical ICU. Ninety-two suicidal, elderly patients (54 women, 38 men) with a mean age of 77 years were included. The mean length of the hospital stay was 7 days (range: 1-45 days). Seventy-six percent of them were intubated and subjected to mechanical ventilation for a mean duration of 3 days. Overdosing on one drug occurred in 46 cases (50%). Toxicological analyses implicated the following medications: benzodiazepines, 50 cases; meprobamate, 26 cases; barbiturates, 24 cases; tricyclic anti-depressants, 17 cases; trichloroethylene, 1 case; insulin, 1 case. Psychiatric history, recorded for 47 patients, revealed previous suicide attempts by 20 of them. Complications were reported in 40 cases (43.5%): respiratory complications, 25 cases; shock, 13 cases; postanoxic coma, 2 cases. The incidence of mortality (13 cases) was 14%. Thirty-three patients were transferred to psychiatric units after release from ICU. During the same period, our ICU admitted 2,762 patients for acute drug poisoning and observed a 1% mortality rate. Thus, morbidity and mortality are higher in the elderly than in younger patients. PMID- 2256588 TI - [Zinc and the immune system]. PMID- 2256589 TI - [Anatomoclinical conference at the Pitie-Salpetriere hospital: cutaneous atrophy, depressive syndrome and hypertension]. PMID- 2256590 TI - [Intestinal spirochetosis in homosexuals infected with HIV. 3 cases]. AB - We report 3 cases of intestinal spirochetosis in homosexuals infected with the human immunodeficiency virus (2 group III and 1 group IV C1, according to the Centers for Disease Control classification) presenting with moderate, chronic diarrhea. The diagnosis was made based on the histological examination of colorectal biopsies showing a layer of spirochetes carpeting the epithelium. Electron microscopy evaluation and culturing of the microorganism provided information on the bacterium's morphology. Metronidazole effectively treated the diarrhea. Intestinal spirochetes, whose existence has been recognized for more than a century, constitute a heterogeneous group of bacteria whose pathogenic role in man remains controversial. The systemic search for these organisms in a large series of patients would help to situate their place among the various etiologies of infectious diarrhea in immunodepressed subjects. PMID- 2256592 TI - [Ocular toxoplasmosis in AIDS]. AB - Since 1983, we have seen 11 cases of toxoplasmic retinochoroiditis in patients with AIDS. Ocular toxoplasmosis appears to be a growing concern in AIDS: 3.3% in 1983, 6.1% in 1988 and 5.9% during the first trimester of 1989. Anti-Toxoplasma gondii antibody titers in the aqueous humour were not conclusive, therefore the diagnosis was based on ophthalmoscopic criteria and on a rapid response to specific therapy. As for brain toxoplasmosis, treatment must be continued indefinitely to prevent relapse. Seven out of 11 patients had cerebral toxoplasmosis, which was diagnosed by computerized tomography (CT) scan. This suggests that a neurological evaluation and a brain CT scan should be performed in all AIDS patients with toxoplasmic retinochoroiditis. PMID- 2256591 TI - [Pulmonary toxoplasmosis in AIDS. Report of 3 cases]. AB - Pulmonary toxoplasmosis in AIDS is rare. Its frequency is estimated to be between 0.2 and 3.7% but is probably underestimated; however, it is lower than that of neurotoxoplasmosis and is rarely identified prior to autopsy. We describe herein 3 cases diagnosed in living patients. The clinical presentation is usually severe interstitial pneumonitis, occurring in profoundly immunodeficient patients. Toxoplasma gondii, the infectious agent, must always be sought in the bronchoalveolar lavage of such patients and is sometimes associated with other opportunistic infectious agents, such as Pneumocystis carinii. PMID- 2256593 TI - [Early-onset pneumothorax in cases of severe pneumocystosis]. PMID- 2256594 TI - [Lymphomatous bone marrow necrosis in a case of AIDS]. PMID- 2256595 TI - [Acute rhabdomyolysis coincident with primary HIV-1 infection]. PMID- 2256596 TI - [Peripheral vestibular syndrome in Behcet's disease. A case report]. PMID- 2256597 TI - [Benign pseudovestibular cerebellar infarction]. PMID- 2256599 TI - [Hypertrophic osteoarthropathy, liver disease and hypogonadism]. PMID- 2256598 TI - [Lyme disease, a new etiology of prolonged fever]. PMID- 2256600 TI - [Primary cardiac lymphoma. A new case]. PMID- 2256602 TI - [Acute rhabdomyolysis induced by fenoverine. 2 cases]. PMID- 2256601 TI - [Surgical treatment of left ventricular rupture 24 hours after latero-basal myocardial infarction]. PMID- 2256603 TI - [Valproic acid: association of a fatal acute hepatitis and pancreatitis]. PMID- 2256604 TI - [Insufficiency of treatment with halofantrine in chloroquinoresistant Plasmodium falciparum malaria in Sierra Leone]. PMID- 2256605 TI - [Determinants of perinatal and infant mortality in Italy 1980-1983]. AB - Determinants of stillbirth, perinatal and infant mortality in Italy have been analyzed using information collected routinely by the Italian Central Institute of Statistics on more than 2,400,000 births and 33,000 infant deaths in the period 1980-1983. Individual records include data on maternal (for example age, education, obstetric history) and fetal (sex, birth weight, gestational week at birth) characteristics. The Italian stillbirth, perinatal and infant (1st-365th day of life) mortality rates were respectively 7.7/1000 births, 16.4/1000 births and 13.5/1000 livebirths for the considered period. Perinatal and infant mortality was impressive in very low birth weight. About 90% of livebirths weighing less than 1000g died within the first year of life, but this percentage decreased to about 45% in babies weighing 1000-1499g. As a whole, low birth weight explained more than 70% of deaths. Further, stillbirth, perinatal and infant mortality rates were higher in male babies, in older women and in higher birth rank. These findings persist, although less markedly, after adjustment for weight. Mortality rates were about 60-70% higher in less educated women. Stillbirth, perinatal and infant mortality rates were 20 to 30% higher in Southern Italy, as compared to the North of the country. This finding was not markedly changed after adjustment for birth weight and maternal age and education, suggesting that socio-economic factors are per se important determinants of perinatal and infant mortality in Italy, and explain in terms of population attributable risk, about 15% of stillbirths or deaths within the first year of life. PMID- 2256606 TI - [Preservation of auditory function in the excision of acoustic neuroma]. AB - Selection criteria for the preservation of auditory function during excision of acoustic neurinoma have been defined for a long time, and the means for a successful achievement of such a goal are widely known. Recruitment of special patients, for whom maintenance of an even deeply altered hearing capacity constitutes a requisite for continuation of professional work has lead us to extend indications for the pre- and retrosigmoid approaches recommended by J.M. Sterkers. The authors present a series of 16 patients, in which a single case of cophosis was deplored. PMID- 2256607 TI - [Pneumolabyrinth and perilymphatic fistula after stapedectomy]. AB - A case of per-surgery discovery of a pneumolabyrinth referred to the oval window is reported. Such was associated with a post-stapedectomy perilymphatic fistula. Revealing clinical signs were invalidating vertigo, transmission-type hearing loss, and tinnitus. Surgical plugging of the fistula caused the dizziness spells to regress completely, as well as improving tinnitus and restoring hearing markedly. Literature data confirm the fact that pneumolabyrinths are always associated with perilymphatic fistulas. Moreover, pneumolabyrinths seem to play an important role in the genesis of cochlear signs accompanying perilymphatic fistulas. PMID- 2256608 TI - [Objective tinnitus and palatal myoclonus. A new therapeutic approach]. AB - The syndrome combining velar myoclonia with objective tinnitus is rare and, in adults, it corresponds most of the times to a neurological lesion of the dento olivary tractus. Its functional manifestations are often invalidating and propounded medical treatments uneffective. The authors report a case in which local injection of botulinus toxin allowed to obtain satisfactory functional improvement. Such therapy may prove useful when conventional management is failing. PMID- 2256609 TI - [Tympanoplasty in the treatment of sequelae of blast injuries of the ear]. AB - This study deals with 40 clinical files relating to auricular blast injury patients with ensuing eardrum perforation, managed either by tympanoplasty or by placement of a healing support. An analysis of the functional symptoms, the size and localization of the perforation; determination of the presence or lack of immediate post-injury infection, and of the degree and type of hearing loss suffered, permits to define the characteristics of postoperative ear status. A comparison of the study results with published data provides for specifying surgical indications and sheds light on the long-term evolution pattern in such patients. PMID- 2256610 TI - [Contribution to the study of the perfect pitch]. AB - Absolute pitch (AP) is the ability to name a note without any reference, since relative pitch (RP) needs for a previous and known tone to be able of such a recognition. We suggest that AP is due to both environmental features and physiological particularity. From the responses of 263 musicians including 169 AP we observed that for AP musical environment in childhood was better, and younger the age of instrumental beginning than for RP. The study of otoacustic emissions evoked by a supraliminar stimulation in 183 musicians ears including 68 AP showed that the echo was significantly greater in case of AP than in case of RP. PMID- 2256611 TI - [The perfect pitch. Birth, delights and death]. AB - The absolute pitch, AP, is the capacity of identifying and/or producing (singing) exact music notes without any prior indication. It appears in prone subjects owing to the assiduous practice of music, and is ruled by the temperament and diapason. It provides an incomparable subjective self-realization and makes it much easier to listen to, understand, write and read music. The false 415 compass, which spread widely as the baroque style became fashionable, stresses the subjects gifted with AP and prevents its appearance in children. This should be a cause of alarm for the medical, as well as administrative, authorities. PMID- 2256612 TI - [Retraction pockets, pathological entity?]. AB - Retraction pockets are not a pathological entity per se but take after various ear diseases, with which they share the same morphological eardrum alterations. The authors believe that any holistic evaluation of retraction pockets, as though these were forming a single group of like pathogenic origin, i.e., tubal dysfunction, would be artificial and raise therapeutic problems. The statistical analysis of the causes for retraction pocket formation provides little information. Otologists are still looking into chronic otitis media and cholesteatoma as a possible, long-suspected, unproved etiology. Electron microscopy and, more particularly, istological-enzymological analyses of mounts prepared by the authors have shown, in some cases, the anomalous presence, in the pocket, of Langerhans' cells, which the authors consider as strongly indicative of cholesteatoma. While confirming the clinical diagnosis, anatomopathological examination allows to differentiate poor-prognosis retraction pockets from benign ones. The pathogenesis of these pockets is still poorly understood. It is the authors' contention that tympanic invagination is more likely traceable to some biopathological/biochemical phenomenon than to occupational mechanical disorders involving the tube. The clinical characteristics of retraction pockets are the basis for their classification into three groups, according to their evolutional tendency. Thus, developing cholesteatomas bear a poor prognosis; sequelae of benign otitis are associated with small risk; lastly, there is a small group of pockets the evolution of which is hard to specify. The authors believe that such differentiation between retraction pockets is mandatory to have a clear picture of therapeutic indications, and to assess the various outcomes. PMID- 2256613 TI - [Effects of loud music on the Garde Republicaine musicians]. AB - The authors report their observations on the auditory status of 76 musicians belonging to a Republican Guard brass band, and give their interpretation of abnormal findings, as they compare percussion with wind instruments and make reference to literature data. Accompanying signs, such as ear fatigue, noise intolerance, tinnitus, ear-aches, disturbance of sleep, psychic disorders, and disturbances of equilibrium are also taken into account as predisposing factors. Lastly, an attempt is made to bring out some of the characteristics that are specific to each instrument. PMID- 2256614 TI - [Rhinoplasty with the external approach. Report of 23 cases]. AB - 23 external rhinoplasties were carried out over a 4-year period between 1986 and 1989. In 19 cases, they related to major malformations or traumatic sequelae requiring a spindle or columella bone graft. In 14 out of these 19 cases, an iliac graft was used. This approach requires a specific technique but it allows an accurate dissection of all the nose structures and grafting under excellent conditions. PMID- 2256615 TI - [Prevention of infectious complications of major upper respiratory and digestive tract surgery by the combination of pefloxacin-amoxicillin-clavulanic acid]. AB - The authors report the results of a therapeutic trial aimed at assessing the efficacy and costs of a twin-antibiotic therapy associating Pefloxacin and Amoxicillin-clavulanic acid for the prevention of infectious complications in major surgery for cancer of the upper respiratory and digestive tracts. The results obtained show 10% of complications, including 6.5% of local complications, with 4.5 to 9.5 day treatments. In our opinion, the poor results noted in the literature in studies on a simple intraoperative antibiotic prophylaxis confirm the need to use a real, so-called "curative" antibiotic therapy over a sufficient period for this type of surgery. This antibiotic therapy must be well tolerated, active for the contaminating organisms, produce no selection of resistant bacteria, and raise hopes to reduce postoperative infectious morbidity, therefore the costs of treatment. PMID- 2256616 TI - [Subcophosis and otosclerosis. Medical and surgical treatment]. AB - The spiral ligament of the stria vascularis is nearly always damaged by otosclerotic foci when the patient is nearly totally deaf because of otosclerosis. Vascular drugs are to be prescribed in such a case, besides the Sodium Fluoride treatment. The Sodium Fluoride is, according to us, the best treatment to arrest the progression of the otosclerotic disease. Sodium fluoride will destroy the proteolytic enzymes damaging the inner ear membranes and the hair of the Corti hair cells. PMID- 2256617 TI - [Gherini-Causse endo otoprobe and HGM argon laser. Value in the surgery of ear abnormalities]. AB - Performing a stapedectomy in a slightly fixed otosclerotic footplate may induce an excessive motion of the labyrinthine fluids, damaging inner ear membranes and Corti hair cells fragilized by proteolytic enzymes. The fluid motion in the cochlear canal is quantic size only. The replacement of a slightly fixed footplate by an ideal compliance and impedance transmitting device, may allow the surgeon to get a tremendous improvement of hearing (as a Meniere disease). The Gherini-Causse multi-use endo-otoprobe combined with a HGM Argon Laser, if associated with a Skeeter Oto-tool drill, looks to be an efficient and safe solution to this otologic surgical challenge. PMID- 2256618 TI - [Presentation of the prototype of a fully implanted cochlear prosthesis]. AB - Description of the prototype of a fully implanted cochlear implant demonstrating the feasibility of a prosthesis with no external component within the next few years. The battery is reloaded by means of electromagnetic induction, and the sound message is received by a subcutaneous microphone, which already has a satisfactory bandwitch and signal-to-noise ratio. This system can be generally applied to most types of permanent intracorporeal stimulation. PMID- 2256619 TI - ["Monosonic" one canal digital implant]. AB - In order to decrease the gap between the single and multichannel cochlear implant efficacy we tried to improve the speech coding strategy of the Monomac, the constant current single channel system which we designed in 1987. Owing to a research computerized system, different strategies have been successively studied in the laboratory on 12 new implanted patients during the first weeks of the post operative period to avoid habituation differences. Results led us to design a miniaturized digital emitter, the Monosonic. This emitter allows the speech therapist to program the frequency band wideness (80-1000 Hz) of the transmitted information, and the threshold level and dynamic range of the stimulating square wave as a function of its frequency. Other strategies are discussed, which have not been yet studied, but may be also programmed. PMID- 2256621 TI - [Atypical implants]. AB - There is theoretically no major surgical problem for implantation. The basic techniques all include on an approach through the windows. The authors describe a solution (which has already been used previously) for cophotic hollowing-out cavities, with a suprapetrosal way and an approach on the hidden aspect of the cochlea. The transcutaneous passage can be displaced from the ear lobe to a depression of the auricle. PMID- 2256620 TI - [Trends in clinical research for one canal cochlear implantation]. AB - Like any modality of perception, the processes of hearing can be divided up into two levels: modular or primary, and symbolic or central. Multiple-canal implantation is rather applied to the former mechanism, single-canal implantation to the latter. A bank of electrical signals recognizable from each other is being built up. It may be utilized in single-canal systems using this vocabulary to form sentences. The proper phonetic feature to be matched will then have to be selected. PMID- 2256622 TI - [Electrophysiologic studies in patients with cochlear implants]. AB - The insertion of reliable extracochlear single-canal cochlear implants in cophotic and subcophotic patients allows the electrical stimulation of the acoustic nerve for rehabilitation, as well as audiovestibular explorations that are no longer possible in the acoustic mode. The authors therefore aim at replacing all these examinations with their Electrical equivalent: --early evoked potentials (E-BERA), --medium-latency evoked potentials (E-MLR), --Event-related evoked potentials (E-P300), for which, to our knowledge, theses are the first recordings, --electrical stapedial reflex, --vestibular stimulations. The method, results and clinical and physiological applications of each method are given, as well as its prospects. PMID- 2256623 TI - [Signal processing in contour implants]. AB - Signal processing by cochlear implants is aimed at transmitting all the acoustic information carried by the human voice, whether in its semantic, esthetic or affective aspects, as an electrical signal. The "translating" approach, which encodes the signal according to the characteristics of the sounds, can only be ideally used in multiple-canal implants. On the contrary, our experience with various single-canal prostheses shows that our patients choose one of these according to the comfort of the signal and to its reliability rather than to the complexity of signal processing: all prostheses produce approximately the same results, whatever the method implemented. The contour implant allows an easy, effective and well-tolerated fitting at low costs. PMID- 2256624 TI - [Tinnitus and implants]. AB - The experience with cochlear implantation at Avicenne hospital prompted us to carry out a retrospective study on tinnitus in a population of operated patients. Improvement or disappearance of the symptoms was noted in all cases. These results, which partly match those found in the literature, are probably produced by rehabilitation inhibiting the "deafferentation" mechanisms in analogy with pain phenomena. In some precise cases, which are described, they led us to proposing implantation even though the main, if not sole, complaint of the patient was tinnitus. PMID- 2256625 TI - [Presentation of a French language protocol for the evaluation of communication improvement in the deaf following implantation]. AB - We have been led to drawing up a procedure of assessment of communication as restored by implantation. This procedure is simple, and can be used by all teams, however complex the material implanted is. It can be implemented for children as well as adults, and for both pre- and post-speech deafness. Our staging allows integrating the implanted patient into the classical description of deafness, while retaining the specific features of electrical stimulation. PMID- 2256626 TI - [Deafness and sarcoidosis]. AB - The cochleovestibular tract is seldom involved by sarcoidosis (about 50 cases have been described since 1948). As a clinical expression of sarcoidosis, deafness is fluctuant in 50% of all cases, bilateral, and most often associated with facial palsy and uveitis, the vestibular reflexes being reduced. The histological studies demonstrate lesions at all levels from the cochlea to be brain stem, but the main mechanism is an infiltration of the arachnoid vessels. The prognosis of sarcoidosis deafness is usually poor in spite of corticosteroid therapy. This paper is illustrated by 3 cases observed in Avicenne Hospital. PMID- 2256627 TI - [Results and indications of cochlear implant in 19 cases of total pre-speech deafness]. AB - From June, 1987, to January, 1900, 19 patients aged 3 to 56 years have been rehabilitated for total deafness occurring prior to the acquisition of speech, ie. before age 2, whatever its cause. Some degree of hearing was achieved in all cases. However, the rate and steadiness of progress in auditory recognition, the daily period of use of the device and the changes in the behavior were inversely proportional to the patient's age. This leads to proposing cochlear implants for all patients, especially children, and all the more largely as they are young. PMID- 2256628 TI - [Use of grafts for the olecranial crest in rhinoplasty]. AB - On the basis of 30 cases of rhinoplasty utilizing an ulnar crest graft performed over the past few years, the authors review the various types of grafts used for rhinoplasty and describe the technique for sampling the ulnar crest graft in detail. They stress the merits of this procedure: --superficial, easily accessible donor site; --simple postoperative period; --minimal scars; --good quality graft requiring minimum modeling. PMID- 2256629 TI - ["Delta" cartilaginous graft in secondary or post traumatic rhinoplasty]. AB - The authors study some cases of surgical revision in post traumatic or secondary rhinoplasty. Cartilaginous grafts with temporal superficialis fascia are recommended. The removal of ear cartilage is used by a posterior approach for the concha cartilage associated with a septum or an alar cartilage removal. They describe the Delta graft associating a concha cartilage supported by a prop (auricular or septal) to repair a loss of substance from the middle or lower third of the nasal pyramid. PMID- 2256630 TI - [Castleman's disease. Report of 2 cases with otorhinolaryngologic involvement]. AB - Two cases of head and neck Castleman disease are reported. Diagnosis is always confirmed by histopathologic examination of the specimen. Head and neck and general localisations are described and discussed. Surgery remains the only treatment of this benign tumor with a high success rate. PMID- 2256631 TI - [Mucocutaneous leishmaniasis. Report of 2 cases]. AB - Two new cases of midfacial granuloma caused by leishmaniasis are reported. This disease is very rare in France but very frequent in South America, where it occurs in two forms called UTA and Espundia. These are described here as well as the means of diagnosis and treatment for this disease. A brief review of the cases published in France seems to indicate that the disease is underestimated in this country. The study of the cases published in other African or European countries shows that all species of Leishmania can produce a midfacial granuloma. PMID- 2256632 TI - [Blepharoplasties. Different techniques of surgery]. AB - The authors, reviewing their own experience of Blepharoplasty (92 cases) since ten years, discuss the principal approaches used depending on the age of the patient, the amount of adipose tissue, the lower lid tarsal and muscular laxity and the quality of the skin excess. On the lower eye lid they emphasize the interest of the transconjunctival approach in young an or coloured people and they undermine a cutaneo-muscular flap in the classical technique. On the upper eye lid, they combine the skin excision with an orbicular muscle strip and in old people with a suspension of the lateral canthus. A good choice between these different approaches avoid the rare complications (ectropion and scleral show) because blepharoplasty must be considered like a "variable geometry" operation. PMID- 2256633 TI - [Gardner's syndrome. Review of the literature. Report of a familial form]. AB - Through a family form study and a literature review, the authors define the symptoms of the Gardner's disease and the checkup to be carried out. Sometimes, the surgical treatment, proposed in an aesthetical purpose, is difficult to carry out due to the tumor location and consistency. Incomplete forms are likely to be more frequent but the risk of colic degeneration remains the same as for the usual form. Examination and multi-departmental care are required. PMID- 2256634 TI - [Should we defend french? A plea for bilingualism]. PMID- 2256635 TI - [Pharyngeal and tracheal flora in intubated neonates: interrelations and role of streptococci]. AB - Fourteen neonates intubated within 48 hours of birth were studied for a mean period of two weeks. None were candidates for antimicrobial therapy. Microorganism loads were evaluated twice a week, quantitatively in the pharynx and semiquantitatively in the trachea. Most microorganisms recovered were Gram positive cocci. All species acquired reached 10(7) CFU/g by the time of the second sampling. All species recovered from the pharynx were recovered from the trachea within 0.25 weeks. The presence of alpha-hemolytic streptococci did not modify the other populations. A colonization pattern similar to that seen in the digestive tract but with specific features due to countercurrent colonization is suggested. PMID- 2256636 TI - [Specific serologic reactions in the cerebrospinal fluid in congenital syphilis and therapeutic implications]. AB - In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies. Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests. Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF; positivity of this test was not correlated with severity of clinical features, CSF protein levels or CSF cytologic findings. The TPHA test was positive in only four children and the VDRL test was consistently negative. These findings are similar to those reported in another group of patients with meningeal involvement proven by the demonstration of IgM in the CSF using recent techniques. Passage of antibodies into the CSF is possible (1 case in this study) but for safety patients with specific IgG in the CSF should be given penicillin in a dosage that provides treponema-killing levels in situ (100,000 U/kg/d). Use of this dosage is recommended whenever sensitive techniques for CSF analysis are not available. PMID- 2256637 TI - [Ultrastructural heterogeneity in primary ciliary dyskinesia syndrome. A case report]. AB - One of the causes of middle lobe syndrome is primary ciliary dyskinesia. This diagnosis was established in an eight-year-old girl by functional studies of the cilia on bronchial and nasal biopsy specimens. The clinical approach to this disease is emphasized and the technical difficulties raised by the diagnosis are discussed. PMID- 2256638 TI - [Gonadal function after cancer treatments in childhood]. AB - Treatments given for childhood malignancies can alter gonadal function by several mechanisms: (1) cranial irradiation may cause either gonadotrophin deficiency or premature puberty. (2) Irradiation of the testes can induce germinal epithelium dysfunction even if the dose delivered is very low; Leydig cell failure occurs beyond 5-6 Gy and ovarian insufficiency beyond 6-7 Gy. (3) Chemotherapy is considerably more toxic for the germinal epithelium of the testes than for the ovaries; alkylating agents are especially toxic. Analysis of the consequences of preparation for bone marrow transplantation by chemotherapy or total body irradiation will be required when longer follow-up are available. PMID- 2256639 TI - [Inflammatory joint disease as a manifestation of Toxocara canis larva migrans]. AB - We report a case of migrating joint involvement occurring as the first manifestation of Toxocara canis larva migrans. We also reviewed the literature on joint disease caused by parasitic infections. Diagnostic criteria are described. We suggest that an immunoallergic mechanism is involved. Furthermore, the therapeutic trial with thiabendazole contributed usefully to the diagnosis in our patient. PMID- 2256640 TI - [Hypocalcemic seizures in two newborn siblings revealing hyperparathyroidism in the mother]. AB - We report the case of a term neonate who developed hypocalcemic seizures due to transient hypoparathyroidism on the sixth postnatal day. His brother had had a similar episode after his birth four years earlier. The mother was free of symptoms and had normal calcium and phosphorus levels at the first evaluation. However, repetition of these determinations with a parathormone assay led to the diagnosis of hyperparathyroidism. A parathyroid adenoma was found and removed surgically. This case-report is the opportunity for reviewing presenting manifestations, diagnostic difficulties, potential complications of this infrequent maternofetal condition, and therapeutic aspects. PMID- 2256641 TI - [Bone complications from chronic etretinate intoxication in children]. AB - Clinical, roentgenographic and biologic features of etretinate bone toxicity in a 13-year-old girl with pachyonychia congenita syndrome are reported. Etretinate is a synthetic derivative of vitamin A that infrequently induces bone and joint abnormalities in children. The following manifestations can be observed: cortical hyperostosis, pain, calcification of tendons, thinning of long bones, demineralization, premature closure of epiphyses, or abnormal remodelling. Onset of these anomalies is often delayed since etretinate has a long half-life. Mechanisms are unknown. We advocate use of the minimum effective dosage and regular monitoring of patients. PMID- 2256642 TI - [Malacoplakia in children. Report of a case with bilateral ureteral stenosis]. AB - A case of severe vesicoureteral malakoplakia with bilateral megaureter in a child is reported. On the basis of a review of the literature, we recall the main characteristics of this condition, particularly concerning pathologic findings and ethiopathogenesis, and underline the difficulty of therapeutic decisions, especially if surgery is considered. PMID- 2256643 TI - [Psychosocial factors and sudden infant death syndrome]. AB - Sudden infant death (SID) is a multifactorial syndrome in which the role of psychosocial factors should be taken into consideration. Deep changes in mores and in the way infants are cared for occurred in the second half of the XXth century. Fragmentation of the traditional family has led to increased isolation of the infant. Significant changes have also occurred in the status of women and have translated into increasingly early separation of the mother from her baby. These factors, together with economic difficulties that carry a risk of preterm birth and intrauterine growth retardation, may be involved in the genesis of SIDS. Difficulties experienced by the mother in relating with her child during the first few months of life, a critical period for interaction, may also play a role. Prevention of SIDS should take psychosocial factors into account and attempt to minimize their effect. PMID- 2256644 TI - [Separation of the distal humeral epiphysis in young children. Radiologic features]. AB - Separation of the distal humeral epiphysis is infrequent in young children. Diagnosis is difficult since the entire condylar region is almost completely composed of cartilage. Marked sequelae occur if the diagnosis is not promptly made and arthrography is required to evaluate the extent of lesions. Two cases in children aged 2 1/2 years and one day are reported. PMID- 2256646 TI - [Meige-Milroy-Nonne disease. Report of a case in a six-month-old infant]. AB - A case of Milroy disease is reported. This very infrequent condition is a familial disease characterized by the presence of lymphedema of the lower limbs. In our patient's family, we identified 12 affected members belonging to four generations. PMID- 2256645 TI - [Value of Imocur in the prevention of recurrent infections in children under six years of age. Results of a multicenter, placebo-controlled trial]. AB - Sixty-four children under six years of age with recurrent ear, nose and throat and/or lower respiratory tract infections (three episodes or more during the previous winter) were included in a double-blind, placebo-controlled study of the oral bacterial immunomodulator Imocur. Imocur provided better individual protection than the placebo throughout the three-month treatment period and the subsequent three-month follow-up period. Among the patients given Imocur, 34% remained free of infection and 37% required no antimicrobial drugs throughout the six-month study period, as compared with 3% and 10%, respectively, among the controls. The number of infectious episodes per patients during the six-month study period was 4.86 among controls versus 1.66 among patients given Imocur. Use of antimicrobial agents was reduced by half among patients treated with Imocur as compared with controls. Tolerance was outstanding, with no adverse effects among treated patients. These results show that Imocur is an effective immunomodulator for the treatment of recurrent ear, nose and throat and/or lower respiratory tract infections in children. PMID- 2256647 TI - Clinical experience with the pulsed-dye laser in the treatment of capillary malformations (port-wine stains): a preliminary report. AB - This preliminary report reviews a series of 70 patients treated with tunable-dye laser therapy for congenital capillary malformations (port-wine stains). Results were reviewed according to age and ethnic group of patients and color and anatomical location of malformations. Red birthmarks were most responsive to treatment in all age groups in all anatomical locations. Purple birthmarks were generally less responsive to laser treatment except in children, who responded well. Scarring and hypopigmentation were minimal (5.7% and 1%, respectively), even in nonwhite patients. Recommendations emerging from this study include testing of infants, as results may vary. Detrimental side effects are rare. A major goal in treating port-wine stains is to avoid both the progression of these lesions through life and the psychological complications that occur during early socialization years in childhood. Pulsed-dye laser treatment offers much promise in these areas. PMID- 2256648 TI - Migration of donor leukocytes from limb allografts into host lymphoid tissues. AB - This study was undertaken in an initial effort to characterize the immunology of extremity transplantation by examining the pattern and kinetics of leukocyte migration from rat limb transplants. Migration of donor leukocytes was evaluated by examining recipient lymphoid tissues with a donor-specific, anti-major histocompatibility complex, class I monoclonal antibody. Double-antibody, two color labeling was used to localize donor cells to specific regions within these tissues. Donor leukocytes, with dendritic cell morphology, were found in the T cell-rich areas of lymph nodes draining the allograft and spleen. The donor cells were present on postoperative days 1 through 3 but were not present on days 5 to 7. Donor leukocytes were not present in distant lymph nodes or liver. These findings indicate a migration of leukocytes, most likely the highly immunogenic dendritic cell, from rat limb transplants to the draining lymphoid tissues. Migration occurs shortly after transplantation and may lead to the sensitization of alloreactive T-cells. PMID- 2256649 TI - Blink reflex recovery after electrical stimulation of the reinnervated orbicularis oculi muscle in dogs. AB - The paralytic lagophthalmos following palpebral nerve neurotmesis and consequent peripheral denervation of the orbicularis oculi muscle is often associated with harmful effects on the exposed cornea. This study investigated how daily electrical stimulation affects the blink reflex recovery of this muscle after its reinnervation. Six dogs underwent unilateral facial nerve neurotmesis with immediate epineurial repair of the palpebral nerve. Three dogs were randomly chosen to receive electrical stimulation of the reinnervated orbicularis oculi muscles for 75 days. The remaining 3 dogs were controls (nonstimulated muscles). During the study, the reinnervated orbicularis oculi muscle electrophysiology and blink reflex recovery were investigated. The Student's t test was used for statistical analysis. The results can be summarized as follows: (1) between 30 and 50 days, the minimum mean stimulus intensities evoking complete up-per palpebral closure of the stimulated muscles were significantly lower than those of the nonstimulated muscles (p less than 0.01) and (2) the stimulated muscles recovered complete closure of the interpalpebral fissure (blink reflex) at 49.6 days, significantly earlier (p less than 0.01) than the nonstimulated muscles (72.6 days). It is concluded that daily electrical stimulation of the orbicularis oculi muscles, if started immediately after epineurial repair of the palpebral nerve neurotmesis, promotes a faster blink reflex recovery in the dog model. PMID- 2256650 TI - The effect of rigid internal fixation on cranial growth. AB - As the use of rigid internal fixation of the facial skeleton has become routine in adults, many craniofacial surgeons have expanded its use to the pediatric population. The effects of miniplate and screw fixation on subsequent craniofacial growth, however, have not been examined. Using 6-week-old rabbits as an experimental model, miniplates were placed across the right coronal suture. Calvarial changes were measured by direct osteometry on dry skull preparations. Compared with the control group, a significant reduction in growth was noted across the plated suture and adjacent bones. Because secondary growth disturbances can be produced with the use of these fixation devices, their use in the pediatric population should be viewed cautiously. PMID- 2256651 TI - External rhinoplasty technique. AB - External rhinoplasty is a valuable tool in the surgical armamentarium of all nasal surgeons. It does not change the dynamics of the operation but offers a new method of exposure. The purpose of this paper is to present our experience with the external rhinoplasty technique in 601 patients, and review the results and complications of this approach to nasal surgery. Two patient reports are presented to demonstrate use of the technique in nasal surgery. PMID- 2256652 TI - Emotional and psychosocial adjustment of women to breast reconstruction and detection of subgroups at risk for psychological morbidity. AB - Thirty-four women who had undergone breast reconstruction after mastectomy for breast cancer were evaluated as to their emotional and psychosocial adjustment. Standardized psychological tests and a self-report questionnaire were used, along with the surgeon's evaluation of the aesthetic success of the reconstruction. Two psychodiagnostic tests were found to be of use in identifying maladjusted women who do not gain optimal benefit from the reconstruction: a questionnaire that evaluates the level of depression (Beck) and another that assesses the level of optimism (Cantrill). No correlation was observed between the surgeon's evaluation of the reconstruction's aesthetic success and the women's satisfaction. It was found that there are two groups of emotional-high-risk women: single women and women receiving adjuvant therapy. It is suggested that emotional-high-risk patients be given psychological support concerning the importance of the mastectomy and their reaction to breast reconstruction. PMID- 2256653 TI - The teres major muscle flap in breast reconstruction. AB - We describe the teres major as a muscle flap. The results of anatomical and radiographic studies demonstrate the surgical anatomy. The details of 4 clinical cases illustrate its application in breast reconstruction. The teres major flap offers advantages over previously described muscle flaps in selected cases of breast and chest contour reconstruction. PMID- 2256654 TI - Miniplate washers for improving lag screw fixation. AB - Increased efficiency in using the lag screw principle for rigid fixation of bone, particularly for fragile cortical or soft cancellous grafts, is facilitated by dispersion of screw head compression forces with a biocompatible metallic washer. Although none is commercially available, such washers may be quickly fashioned from the residua of any adaptation miniplate in quantities as required. PMID- 2256655 TI - The role of the plastic surgeon in the treatment of Gardner's syndrome: a report of two cases. AB - Gardner's syndrome is a hereditary disease manifested by multiple colonic polyps that progress to malignancy at an early patient age and also manifested by multiple lesions of the different germ layers including sebaceous cysts, lipomas, fibromas, and osteomas of the facial bones. The plastic surgeon often is asked to treat these patients for the more mundane manifestations of the disease such as inclusion cysts or lipomas. At times, however, the plastic surgeon may be faced with an unusual presentation. Two such unusual cases are presented here, the first being a hemangioma of the hand, which has never been described in a patient with Gardner's syndrome, and the second being a fibroma of the left cheek requiring excision by an intraoral approach. PMID- 2256656 TI - The use of cryopreserved venous allografts in free tissue transfers--practical and aesthetic considerations. AB - A case in which multiple cryopreserved allograft saphenous veins were used as vein grafts for a difficult mandible reconstruction with a free tissue transfer is reviewed. Use of allograft veins was recently reported for lower limb vascular reconstruction but not for free tissue transfers. Such grafts may represent a viable alternative to the use of autologous vein grafts and have the potential to decrease operating time and avoid necessary scars. PMID- 2256657 TI - The paleopathology of the liver. AB - Paleopathology, the study of disease in ancient remains, adds the dimension of time to our study of health and disease. The oldest finding relating the liver to disease is indirect skeletal evidence of hypervitaminosis A in an early human fossil owing to the ingestion of excessive amounts of animal liver. The earliest evidence of pathologic change in the liver is an example of schistosomal cirrhosis in a 3200 year old Egyptian mummy. Lipofuscin pigment has been identified in the liver of a 1600 year old Eskimo mummy. An experimental study suggests that the potential exists for identifying a wide range of hepatic pathology in mummified remains. PMID- 2256658 TI - Problems with the measurement of apolipoproteins AI and AII. AB - There is considerable evidence demonstrating that increased levels of low density lipoprotein (LDL) cholesterol and decreased levels of high density lipoprotein (HDL) cholesterol are associated with coronary artery disease (CAD). Yet, these lipoprotein markers are insensitive for identifying risk of CAD. Measurement of subcomponents of HDL may offer more sensitive markers. Investigators have focused on protein components (apolipoproteins) of HDL as a potentially important marker. Unfortunately, because much of the immunoreactivity of apolipoproteins is hidden as a result of an association with lipids, it is difficult to measure them accurately. Detergents and other denaturing agents have been used to expose immunoreactivity. Poor correlations among different methods suggest that some detergents presently used may not be adequate for effective measurement of apolipoprotein (APO) AI. Studies using denaturing agents to probe HDL particles indicate that APO AII immunoreactivity is more resistant to exposure than that of APO AI. Data presented here indicate that the immunoreactivity of APO AII can be increased up to 50 percent by treatment with 4M guanidine provided the concentration of guanidine is diluted to less than 50 mM in the assay system. Previous studies failed to notice this effect because high levels of guanidine inhibited the antibody-antigen reaction in the immunoassay, making it appear that APO AII had not been exposed. It is concluded that with our present state of knowledge, it is unclear which, if any apolipoprotein assays, are adequately designed to achieve optimal exposure of antigenic sites, but that pretreatment with guanidine may be a simple, effective way to optimize APO AI and APO AII assays for clinical purposes. PMID- 2256659 TI - Quality assurance in the intensive care unit--monitoring hematocrit orders. AB - To provide a quality assurance (QA) study in the intensive care unit (ICU), hematocrit orders were monitored for five months (September 1989-January 1990) in an attempt to determine appropriate practice. Computer prints of all hematocrits (hct) ordered in the ICU were reviewed. Of all patients admitted to the unit in this time (528), 61 percent (319) had hematocrits ordered. The maximum number ordered per day varied from one to six with a mean of 1.4. All patients having three or more hcts per day (46) were reviewed by one or more of the authors to determine the circumstances. The patients consisted of 27 men and 19 women between the ages of 16 to 92 years with a median of 70 years. Thirty-three (72 percent) were 60 years of age or older. Twenty-seven were patients with active bleeding. Most had need for hct clearly delineated. In 11 others, justification was not clearly delineated, but resulted from blanket orders when vital signs were stable. In eight patients, multiple hcts were not necessary, but were obtained because of confusing orders or clerical error. These observations suggest that QA review of laboratory orders from the ICU will detect a few abuses and will find some patients whose laboratory tests could be optimized in an educational setting. PMID- 2256660 TI - Misdiagnosis of acute myocardial infarction. AB - A total of 979 cardiac profiles were reviewed. Seventeen cases were found to have elevated CK-BB by electrophoresis and were misidentified by the immunoinhibition/immunoprecipitation technique as elevated creatine phosphokinase (CK-MB). Eleven of the 17 cases also had elevated lactate dehydrogenase (LD) LD 5/LD-1 ratio; five cases were motor vehicle accident (MVA), four cases were prostatic carcinoma (PC), and one case each of breast carcinoma and coronary heart disease. One case of PC and one of MVA with a preliminary clinical diagnosis of acute myocardial infarction (AMI) were presented. Our findings underscore the importance of electrophoretic confirmation of the presence of CK MB when detected by a quantitative technique. Clinicians should consider the possibilities of PC or other cancers when elevated "CK-MB" is present in conjunction with a raised LD-5/LD-1 ratio in patients who fail to show clear-cut clinical evidence of AMI. The mechanism of elevated CK-BB and LD-5/LD-1 ratio in PC patients are discussed. PMID- 2256661 TI - Histologic characteristics of Campylobacter pylori (Helicobacter pylori) mediated gastritis. AB - One hundred-nineteen specimens were reviewed to determine whether or not there were histologic changes specific for Campylobacter pylori (CP), (Helicobacter pylori) mediated gastritis. Hematoxylin and eosin (H&E), Brown-Hopp, and Wright Giemsa stained sections were examined independently by two pathologists for (a) the presence of acute cryptitis, (b) percent and degree of crypt involvement, and (c) spectrum of inflammatory cells within the lamina propriae. The amount of mucus was quantified on the Periodic Acid Schift (PAS)-Alcian Blue stain sections. Changes in the character of the mucus were noted by using both the PAS Alcian Blue and the High Iron Diamine-Alcian Blue. A positive specimen for Campylobacter pylori (CP+), (Helicobacter pylori) was defined as one in which curved or spiral shaped microbes were identified on Wright-Giemsa and Brown-Hopp stain. Seventy-eight specimens were CP+ and 41 CP-. Statistically significant histologic findings included the extent and degree of superficial cryptitis and the preponderance of plasma cells in CP+ cases. These findings confirm aspects seen in an animal model and suggest that there is an histologic pattern consistent with C. pylori (Helicobacter pylori) mediated gastritis. PMID- 2256662 TI - Lymph node pathology of acquired immunodeficiency syndrome (AIDS). AB - There has been a recent notable increase in the number of patients in the United States seropositive for the human immunodeficiency virus (HIV) and also an increase in the number of otherwise healthy homosexuals with persistent generalized lymphadenopathy (PGL). Lymphoid tissue appears to be a favorite target for the initial viral infection, subsequent opportunistic infections, and associated neoplasms. Therefore, evaluation of PGL is important in understanding the nature of the disease. Biopsies of the acquired immunodeficiency syndrome (AIDS) lymph nodes show a spectrum of abnormal lymphoid proliferations, eventual lymphoid depletion, Kaposi's sarcoma, and malignant lymphoma. Although the individual features of AIDS-related lymphadenopathy may not be specific, the constellation of histologic, immunologic, ultrastructural, and fine needle aspiration findings is characteristic. PMID- 2256663 TI - Human immunodeficiency virus western blot tests: comparisons and considerations. AB - Human immunodeficiency virus (HIV) Western Blot (WB) tests are used as an aid in the diagnosis of acquired immunodeficiency disease syndrome (AIDS) and related disorders. The object of this study is to examine and compare the results of four commercially available HIV WB methods. Sera from 974 persons were tested by four (Kits I, II, III, and IV) HIV WB methods from different vendors. The HIV WB were interpreted by recognized criteria published in Morbidity and Mortality Weekly Report. RESULTS: 65 percent of the referred specimens received were HIV enzyme immunoassay (EIA) repeatedly reactive (R), and 35 percent of the referred specimens were HIV EIA nonreactive (NR). The EIA (NR) sera showed the greatest variability for HIV WB results, especially in the indeterminant (I) category. The HIV WB tests commercially available vary in sensitivity and specificity. Standarization of materials and controls and the use of uniform interpretation criteria are needed. PMID- 2256664 TI - Peroxidation of linolenic acid--catalysis by transition metal ions. AB - Numerous studies have demonstrated that several indices of oxidative damage are enhanced in target tissues of rodents exposed to various transition metal ions. Whether or not these indices represent primary or secondary effects are not known, since tissues injured by other mechanisms are susceptible to an increased rate of lipid peroxidation (LP). In the current study, the reaction mixtures (metal ions with linolenic acid) were preincubated at 37 degrees C for 24 hours prior to the measurement of malondialdehyde (MDA) by liquid chromatography, and conjugated dienes at 233 nm. These metal-catalyzed reactions were also compared in the presence of butylated hydroxytoluene (BHT), a free radical scavenger. Our results showed that Cd(II), Co(II), Cu(II), Fe(II & III), Mn(II), and Ni(II) all significantly increased the concentration of MDA and conjugated dienes over LA controls (P less than 0.001 by Mann-Whitney test). The production of MDA and conjugated dienes was also increased by Al(III) but to a lesser degree (P less than 0.05 and 0.01, respectively); As(V) did not increase either index. The addition of butylated hydroxytoluene (BHT) to the reaction mixtures significantly reduced the production of MDA (P less than 0.001). These in vitro studies support prior in vivo reports that the primary mechanism of the acute toxic effects of these metal ions is due, at least in part, to metal-catalyzed peroxidation of polyunsaturated fatty acids. PMID- 2256666 TI - American education--1990. PMID- 2256665 TI - Phenylhydrazine is a mitogen and activator of lymphoid cells. AB - Rats were administered a single injection of phenylhydrazine (PHZ) which induced an hemolytic anemia that reached maximal levels two to four days following injection. This was accompanied by a leukocytosis which was most pronounced four to six days after injection; lymphocytes and monocytes accounted for 75 percent to 80 percent of the leukocyte count, respectively. All peripheral blood cell values, including the red cell count and hematocrit, returned to their pre injection levels by the 11th post-injection day. Analysis by flow cytometry of peripheral blood mononuclear cells (PBMC) isolated from PHZ-treated rats by Ficoll-Hypaque gradient separation showed a marked increase in the B cell population of the peripheral blood. This was also seen in cultures of PBMC obtained from untreated rats following incubation with PHZ. Cultures of PBMC obtained from rats four to five days after PHZ injection which were incubated with pokewood mitogen (PWM) or phytohemagglutinin (PHA) showed significant increases in blastogenesis as indicated by [3H] thymidine incorporation when compared to cultures of PBMC obtained from untreated rats incubated with these mitogens. Incubation of cultures of PBMC obtained from untreated rats with PHZ significantly increased blastogenesis in cultures of five day duration. Atypical and blastic lymphoid cells were evident in cytosmears of PBMC isolated from PHZ treated rats and also in sections of PBMC pellets studied using the transmission electron microscope. Serum of the PHZ-treated rats contained elevated immunoglobulin titers as measured by radial immunodiffusion. The results show that PHZ stimulates lymphoid cell blastogenesis and can sensitize circulating lymphoid cells to PHA and PWM indicating that PHZ is capable of stimulating the immune system of the rat. PMID- 2256667 TI - [Chylous ascites in adults: etiological, therapeutic and prognostic aspects. Apropos of 35 cases]. AB - Chylous ascites is a rare disease which often poses difficult problems in diagnosis and management. We reported a series of 35 patients with chylous ascites, seen between 1976 and 1989. Diagnosis of chylous ascites was made on: (1) a milky appearance of ascites; (2) an ascitic concentration of triglycerides higher than in serum and higher than 1.5 mmol/l. Incidence was about 1/8 850 admissions. Cancers (mainly lymphomas and abdominal carcinomas), cirrhosis and retroperitoneal surgery accounted for more than 90 p. cent of cases. In all cases of cancer the tumor was extensive, and the prognosis was poor with a one year mortality rate of 80 p. cent. The two postoperative chylous ascites without cirrhosis were cured, after treatment with medium chain triglycerides in one case, and surgical repair in the other case. Chylous ascites in cirrhosis, spontaneous or after porto-systemic shunt, became refractory in 13 of 15 patients, and the one year mortality rate was high (69%). PMID- 2256668 TI - [Chronic idiopathic intestinal pseudo-obstructions]. PMID- 2256669 TI - [Pathological anatomy in chronic intestinal pseudo-obstructions]. PMID- 2256670 TI - [Radiology of chronic intestinal pseudo-obstructions]. PMID- 2256671 TI - [Azathioprine-induced acute pancreatitis]. PMID- 2256672 TI - A review of the role of 70 kDa heat shock proteins in protein translocation across membranes. AB - The compartmentalization of essential hsp70 proteins indicates that hsp70s carry out crucial functions in several compartments of the cell. The use of conditional mutants has allowed study of the cellular processes that require hsp70 function. For efficient translocation of proteins across membranes hsp70s are required in the cytoplasm, as well as in the matrix of mitochondria and in the lumen of the endoplasmic reticulum. PMID- 2256673 TI - The structure and function of small heat shock proteins: analysis of the Saccharomyces cerevisiae Hsp26 protein. PMID- 2256674 TI - DNA supercoiling, chromatin structure and the regulation of gene expression. PMID- 2256675 TI - The OxyR regulon. AB - Treatment of Salmonella typhimurium and Escherichia coli cells with low doses of hydrogen peroxide results in the induction of thirty proteins and resistance to killing by higher doses of hydrogen peroxide. The expression of nine of the hydrogen peroxide-inducible proteins, including catalase, glutathione reductase and a novel alkyl hydroperoxide reductase is controlled by the positive regulator oxyR. OxyR is homologous to the LysR-NodD family of bacterial regulatory proteins and binds to the promoters of oxyR-regulated genes. The oxidized but not reduced form of the OxyR protein activates transcription of oxyR-regulated genes in vitro suggesting that oxidation of the OxyR protein brings about a conformational change by which OxyR both senses and transduces an oxidative stress signal to RNA polymerase. PMID- 2256676 TI - Heat shock translational control in cell-free system. PMID- 2256677 TI - Adaptation of Escherichia coli to elevated temperatures: the metA gene product is a heat shock protein. PMID- 2256678 TI - Promoter function and in situ protein/DNA interactions upstream of the yeast HSP90 heat shock genes. AB - We have mapped in vivo protein/DNA interactions within the upstream regulatory regions of the two yeast HSP90 genes, and have begun mutagenizing footprinted sequences in an effort to identify the cis-acting determinants of heat shock transcription. Genomic footprinting of the HSP82 promotor using chemical and enzymatic nucleases reveals that irrespective of transcriptional state, the most proximal of three heat shock elements, HSE1, is occupied along both sugar phosphate backbones as well as within its major groove, while the TATA box is bound along both sugar-phosphate backbones. Distorted DNA structure is associated with each constitutively bound factor: protein binding to HSE1 appears to induce a local A-form-like helical conformation, whereas occupancy of the TATA box is associated with strand-specific nuclease hypersensitivity of an adjacent polypurine tract. In situ mutagenesis experiments indicate that HSE1 is absolutely required for both basal and induced expression, and that basal transcription can be preferentially abolished by point mutations within this sequence. In contrast, point mutations within the TATA element have the reverse effect, as induced transcription is more significantly affected. Similar to HSE1 point mutants, we have found that basal transcription is preferentially repressed by an HMRE silencer element when it is transplaced approximately 1 kb upstream of the HSP82 start site. Finally, a complementary footprinting analysis of the upstream region of the constitutively expressed HSC82 gene reveals the presence of three discrete protein complexes. These map to the TATA box, the promotor distal heat shock element, C.HSE1, and a novel sequence upstream of C. HSE1, suggesting that the 10-fold higher basal transcription of HSC82 stems, at least in part, from a non-HSE-binding factor. PMID- 2256679 TI - Roles and regulation of the heat shock sigma factor sigma 32 in Escherichia coli. PMID- 2256680 TI - Stress proteins and mitochondrial protein import. PMID- 2256681 TI - Stress proteins and the immune response. PMID- 2256683 TI - Nonepidermal origin of cutaneous melanoma in a small congenital nevus. PMID- 2256682 TI - Trehalose in yeast, stress protectant rather than reserve carbohydrate. AB - Trehalose and glycogen are generally regarded as the two main reserve carbohydrates in yeast. However, several lines of evidence suggest that trehalose does not primarily function as a reserve but as a highly efficient protecting agent to maintain structural integrity of the cytoplasm under environmental stress conditions. PMID- 2256684 TI - Spindle and epithelioid cell nevus (Spitz nevus). Natural history following biopsy. AB - A clinical follow-up study of 49 cases of spindle and epithelioid cell nevus is presented to address the question about the potential for local recurrence. Only 19 (39%) of the 49 lesions were initially excised en toto, and the remainder (30 cases) had positive margins; six of the latter spindle and epithelioid cell nevi were reexcised, and no evidence of a residual nevus was found in five of the six cases. There were no recurrences in the 49 patients during an average follow-up period of 5.0 years (range, 1 to 10 years). The rarity of recurrent spindle and epithelioid cell nevus would justify a conservative approach to management, with clinical follow-up alone recommended after a subtotal excision, when the pathologic diagnosis is unequivocal. PMID- 2256685 TI - Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates. AB - We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed. PMID- 2256686 TI - Type VII collagen and 19-DEJ-1 antigen. Comparison of expression in inversa and generalized variants of recessive dystrophic epidermolysis bullosa. AB - The expression of type VII collagen and 19-DEJ-1 antigen was examined in 73 and 71 patients, respectively, with recessive dystrophic epidermolysis bullosa (RDEB), comprising gravis, mitis, inversa, and indeterminant subsets, to better determine the specificity and sensitivity of two monoclonal antibodies directed against these dermoepidermal junction-specific epitopes. Type VII collagen (LH 7:2 epitope) was usually absent (in 90%) in patients with the gravis variant of RDEB, whereas its expression was most often diminished (in 67%) in those with the mitis form of the disease. Only 2% and 5% of patients with gravis and mitis variants, respectively, had apparent normal amounts of type VII collagen within their skin. In contrast, six (86%) of seven patients with the inversa variant had normal expression of the antigen. Only 25% of all patients with RDEB lacked the 19-DEJ-1 antigen; of these, however, most had the gravis variant, although absence or diminution was also infrequently observed in those with the mitis and inversa forms. Intermediate findings were noted in patients classified as having indeterminant forms of RDEB. Some variability in antigen expression was also noted among affected siblings. We conclude that assessment of expression of the LH 7:2 epitope of type VII collagen may be diagnostically useful, although considerable overlap does exist between individual patients with gravis and mitis forms. 19-DEJ-1 expression is a far less sensitive probe in RDEB, although such data may prove useful in the assessment of newborns lacking the characteristic features of gravis disease. In addition, based on our experience with inversa RDEB, it would appear that altered expression of type VII collagen cannot be attributed to blister formation in this latter rare subset, since this antigen is usually strongly detected along the dermoepidermal junction, even in perilesional skin sites. PMID- 2256687 TI - Unusual skin tumors in Langerhans' cell histiocytosis. AB - A case of Langerhans' cell histiocytosis with unusual skin manifestations in the form of multiple large skin tumors is described. The skin lesions responded partially to chemotherapy with etoposide and prednisone, and residual lesions were excised surgically. The patient developed central diabetes insipidus during treatment. PMID- 2256688 TI - Dual publication and manipulation of the editorial process. PMID- 2256689 TI - The face of leprosy in the United States today. PMID- 2256690 TI - The Archives of Dermatology 1990 Annual Trainee Award is presented to Richard L. Gallo, MD. PMID- 2256691 TI - Umbilical lesion in a young child. Omphalomesenteric duct (OMD) polyp. PMID- 2256692 TI - Purple depressions on the trunk and extremities. Atrophoderma of Pasini and Pierini. PMID- 2256693 TI - Human orf. PMID- 2256694 TI - Histology of lupus erythematosus. PMID- 2256696 TI - Skin tags do not contain cutaneous nerves. PMID- 2256695 TI - Accuracy of melanoma diagnoses. PMID- 2256697 TI - Congenital circumareolar telangiectasias: a uniquely distributed vascular malformation. PMID- 2256698 TI - Discoid lupus erythematosus-like skin changes in patients with autosomal recessive chronic granulomatous disease. PMID- 2256699 TI - Porphyria cutanea tarda and acquired immunodeficiency syndrome: case reports and literature review. PMID- 2256700 TI - Universal dyschromatosis associated with photosensitivity and neurosensory hearing defect. PMID- 2256701 TI - Complete response of metastatic basal cell carcinoma to cisplatin chemotherapy: a report on two patients. PMID- 2256702 TI - A flow cytometric comparison of DNA content and glutathione levels in hepatocytes of English sole (Parophyrs vetulus) from areas of differing water quality. AB - English sole (Parophyrs vetulus) in Puget Sound, Washington, USA are at risk of hepatocarcinogenesis specifically in areas adjacent to polluting industrial effluents. A question concerning population and ecosystem survival is whether any of the effects of etiopathologic change are reversible. This has been approached by looking for evidence of tumor accelerating effects in an exposed population. Cellular parameters were determined by flow cytometry for hepatocytes of English sole. Cells containing hyperdiploid DNA not present in fish from reference waters, Port Madison, were found in all non-tumor-bearing and tumor bearing fish taken from a polluted site, Eagle Harbor, where incidence of hepatic neoplasia approaches 30%. Induction of altered DNA content in the exposed general hepatocyte population suggests environmental induction rather than an association with lesions per se. In contrast, glutathione levels in hepatocytes (0.8-3.2 nmol/mg protein), were little influenced by the exposure site, consistent with the apparent lack of protection against chemically induced carcinogenesis in English sole. Association of altered DNA content with exposure site is significant for its potential contribution to biological acceleration and evidence of tumor promotion found at the tissue and organismic levels. The results support the notion that hepatocarcinogenesis in English sole in Eagle Harbor has a multi-year exposure etiology, in which potentially reversible accelerating influences have a role, and that glutathione conjugation is an inadequate mode of detoxification for these fish. PMID- 2256703 TI - Assessment of chemical toxicity using mammalian mitochondrial electron transport particles. AB - New spectrophotometric bioassay procedures have been developed for evaluating chemical toxicity, using electron transport particles isolated from bovine heart mitochondria, based on the ability of many toxic chemicals to interfere with the integrated function of electron transport enzymes. The sensitivity of the mitochondrial assay is compared to published sensitivities of other in vivo and in vitro toxicity testing methods. Regression analysis of logarithmically transformed toxicity values for 42 chemicals, including 8 pesticides, 5 drugs, 6 metals, 8 alcohols, 5 respiratory inhibitors, 4 phenols, and 2 phthalates, indicates excellent correlation between the sensitivity of the new assays and the sensitivity of mammalian cytotoxicity studies (r2 = 0.86). Data from aquatic exposure toxicity tests conducted in fish are also highly correlated with the mitochondrial assay results (r2 = 0.79). However, correlation of data from these methods with median lethal dose studies conducted in rats is not as good because of the inability of in vitro and aquatic exposure analyses to account for the gastrointestinal absorption, hepatic metabolism, and excretion processes which modify toxic responses following oral administration. PMID- 2256704 TI - Selenium in wetlands and waterfowl foods at Kesterson Reservoir, California, 1984. AB - Kesterson Reservoir (Kesterson) received subsurface agricultural drainwater containing high levels of salts and selenium from farmland in the San Joaquin Valley of California. The accumulation of selenium in wetlands and waterfowl foods at Kesterson was investigated during May, August, and December of 1984. High concentrations of selenium vegetation, and aquatic insects. Mean selenium concentrations in aquatic plants and insects ranged from 1.5 to 170 micrograms/g dry weight and were about 11 to 290 times those found at a nearby reference site. Concentrations in some waterfowl food plants and insects at Kesterson were up to 64 times those reported to be a health hazard to birds. Selenium concentrations were more seasonally variable in aquatic plants than in aquatic insects. Few differences in selenium accumulation were found among ponds. Deposition of selenium in plant parts was not uniform; rhizomes contained higher concentrations than seeds and leaves were intermediate. Most biota bioaccumulated maximum selenium concentrations that were 1,000 to nearly 5,000 times the concentration in the water. PMID- 2256705 TI - Subacute toxicity of dietary heptachlor to mink (Mustela vison). AB - Mink were fed diets that contained 0, 12.5, 25, 50, or 100 mg/kg active ingredient heptachlor (as technical grade formulation) for 28 days followed by a 7-day observation period to determine the toxicity of this insecticide to mink. Diets that contained 25 mg/kg, or more, heptachlor resulted in a significant decrease in feed consumption, while 50 mg/kg, or more, heptachlor caused a significant reduction in body weights. Mortality (37.5%) occurred only in the group fed 100 mg/kg heptachlor. The dead mink showed neurological signs of toxicity prior to death. Animals fed 100 mg/kg heptachlor also had reduced relative weights of the spleen and kidney and increased relative weight of the adrenal glands when necropsied at the time of death or at the termination of the study. PMID- 2256706 TI - Toxic interaction of tetraisopropylpyrophosphoramide and propoxur: some insights into the mechanisms. AB - Propoxur with a non-toxic dose (5 mg/kg) administered intraperitoneally (ip) in tetraisopropylpyrophosphoramide (iso-OMPA, 1 mg/kg) pretreated rats subcutaneously, sc) produced severe intoxication of anticholinesterase nature. The observed severity was comparable to that caused by an acute sublethal dose of propoxur (15 mg/kg) suggesting at least threefold potentiation of toxicity. Either drug given alone produced neither signs of toxicity nor alterations in acetylcholinesterase (AChE) activity, while carboxylesterase (CarbE) activity was markedly reduced indicating tremendous nonspecific binding. The administration of iso-OMPA followed by propoxur elicited inhibition of AChE to a critical level and produced severe intoxication. These results suggested that iso-OMPA induced potentiation of propoxur toxicity stemmed through irreversible inhibition of CarbE. PMID- 2256707 TI - Recovery of 1,3-, 2,3-dichloropropenes, 1,2-dibromo-3-chloropropane, and o-, p dichlorobenzenes from fatty and non-fat foodstuffs by liquid extraction technique. AB - Food samples including fatty, non-fatty, grain-based, and nongrain-based types were fortified with the following five nematocides and fumigants: 1,3 dichloropropene, 2,3-dichloropropene, 1,2-dibromo-3-chloropropane, o dichlorobenzene, and p-dichlorobenzene. Then, depending on sample consistency and type, the samples were diluted in, or extracted with organic solvent such as isooctane. A few of the high-fat extracts were passed through Florisil to remove excess fat or endogenous interferences. Analysis of the initial or cleaned up extracts was done by gas chromatography (GC) at 90 degrees C. The dichloropropenes were determined on 20% OV-101 columns with electron-capture and Hall electroconductivity detectors. The dichlorobenzenes and 1,2-dibromo-3 chloropropane, which elute beyond 30 min on the above columns, were determined on 5%-loaded columns using the same detectors. All five analytes were recovered from these techniques. Mean analyte recovery following a direct dilution or extraction was 83%, and following the Florisil cleanup step, was 52%. In 1986, a fumigant survey of about 200 foodstuffs by using this overall technique gave no findings of the five compounds studied here. PMID- 2256708 TI - Peroxidase-catalyzed oxidation of chlorophenols to polychlorinated dibenzo-p dioxins and dibenzofurans. AB - Chlorophenols are transformed in vitro to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) by peroxidase-catalyzed oxidations. This is demonstrated with bovine lactoperoxidase as well as horseradish peroxidase, and with 3,4,5- and 2,4,5-trichlorophenol (TrCP). The yield of total PCDD/Fs with lactoperoxidase was 11 micrograms per g 345-TrCP and 10 micrograms per g 245-TrCP, of which 2,3,7,8-substituted PCDD/Fs constituted 8.5 and 2.2 micrograms/g, respectively, corresponding to 0.85 and 1.2 micrograms/g of Nordic TCDD-equivalents. PMID- 2256709 TI - Indoor radon and well water radon in Virginia and Maryland. AB - The domestic use of radioactive water has long been a cause for concern, but only a few studies have examined prolonged exposure to radionuclide concentrations found in natural settings. This paper reports on the indoor radon concentrations from 1,500 homes in northern Virginia and southern Maryland and well water radon from 700 homes in the same area. Indoor radon concentrations are almost all between 1 and about 40 pCi/L. The winter season shows the highest values with about 40% of the homes over the US EPA action level of 4.0 pCi/L. The summer season shows the lowest values with about 25% of the homes over this level. This seasonal variation is related to home ventilation. Waterborne radon in homes with private well ranges from about 100 pCi/L to about 8,000 pCi/L. In small homes, indoor radon can be significantly increased by outgassing of the home water supply, even at water radon levels of less than 10,000 pCi/L. PMID- 2256710 TI - Occupational sunlight exposure and melanoma in the U.S. Navy. AB - Melanoma is the second most common cancer, after testicular cancer, in males in the U.S. Navy. A wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the Navy. Person-years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the Naval Health Research Center. A total of 176 confirmed cases of melanoma were identified in active-duty white male enlisted Navy personnel during 1974-1984. Risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure: (1) indoor, (2) outdoor, or (3) indoor and outdoor. Compared with the U.S. civilian population, personnel in indoor occupations had a higher age-adjusted incidence rate of melanoma, i.e., 10.6 per 100,000 (p = .06). Persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate, i.e., 7.0 per 100,000 (p = .06). Incidence rates of melanoma were higher on the trunk than on the more commonly sunlight-exposed head and arms. Two single occupations were found to have elevated rates of melanoma: (1) aircrew survival equipmentman, SIR = 6.8 (p less than .05); and (2) engineman, SIR = 2.8 (p less than .05). However, there were no cases of melanoma or no excess risk in occupations with similar job descriptions. Findings on the anatomical site of melanoma from this study suggest a protective role for brief, regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin D to suppress growth of malignant melanoma cells in tissue culture. A mechanism is proposed in which vitamin D inhibits previously initiated melanomas from becoming clinically apparent. PMID- 2256711 TI - Accumulation of erythrocyte nucleotides and their pattern in lead workers. AB - Nucleotides in erythrocytes of lead-exposed subjects were analyzed by high performance liquid chromatography (HPLC). Most of the pyrimidine levels correlated well with blood lead concentrations (Pb-B) and pyrimidine 5' nucleotidase (P5N) activity. Highly significant correlations were found between Pb-B and uridine 5'-diphosphate-glucose (UDPG), cytidine 5'-triphosphate (CTP), or CDP-choline (CDPC). The levels of these compounds were sharply elevated when P5N activity was reduced to levels less than 7 mumole/h.g hemoglobin (Hb), which corresponded to a Pb-B of 60 micrograms/100 g. Therefore, concentration of these nucleotides may provide a useful index of lead poisoning. Adenosine 5' triphospate (ATP) concentrations were correlated negatively with Pb-B, whereas adenosine 5'-monophosphate (AMP) concentrations were correlated positively with Pb-B. These results suggest that lead affects not only pyrimidine nucleotide metabolism but also purine nucleotide metabolism (energy production system). PMID- 2256712 TI - High mortality and shortened life-span in patients with itai-itai disease and subjects with suspected disease. AB - A follow-up study was conducted from 1967 to 1987 for patients diagnosed as having itai-itai disease, subjects who were suspected of having the disease, and controls. Ninety-five subjects per category were selected after matching for age, sex, and residential area. The cumulative survival rate of the patients who had a definite diagnosis of itai-itai disease was significantly lower than that of the control group in every period after the first 3 y. The cumulative survival rate of the subjects who were suspected of having itai-itai disease and who had severe renal dysfunction due to cadmium pollution was significantly lower than that of the control group. These results demonstrate (1) the enduring negative influence of itai-itai disease on prognosis and (2) that the cadmium pollution-induced renal disorder adversely affects the health of the inhabitants of a cadmium polluted area. PMID- 2256713 TI - Respiratory health of plywood workers occupationally exposed to formaldehyde. AB - This study was undertaken to enlarge our understanding of the adverse health effects of formaldehyde exposure in the workplace and community environment. The respiratory health status of 186 male plywood workers was evaluated by spirometric tests, respiratory questionnaires, and chest x-rays. Area concentrations of formaldehyde were measured in the work environment and found to range from 0.28 to 3.48 ppm. The average personal exposure was to 1.13 ppm of formaldehyde. Exposure to formaldehyde was associated with decrements in the baseline spirometric values, i.e., forced expiratory volume in 1 sec (FEV1.0), forced expiratory volume/forced vital capacity (FEV/FVC), and FEF25%-75%, and with several respiratory symptoms and diseases, including cough, phlegm, asthma, chronic bronchitis, and chest colds. The results of the study support the hypothesis that chronic exposure to formaldehyde induces symptoms and signs of chronic obstructive lung disease. PMID- 2256714 TI - Epidemiologic research using existing databases of environmental measures. AB - When detailed information on individuals is not available, databases of environmental measures are sometimes used in epidemiologic studies to provide data on human exposure. The use of such databases is based on the assumption that the data are representative of individual human exposure and are applicable to the study. Twenty-six databases that contained data on the environment pertaining to California were summarized and evaluated by categorical criteria of spatial and temporal precision, availability, amount of quantitative information, "machine-readability," and type of environmental measure. PMID- 2256715 TI - Maternal serum fructosamine and maternofetal glucose and insulin homeostasis in normal pregnancy. AB - Well-defined normal values are necessary to identify pregnancies complicated by gestational diabetes (GD) and thus further reduce perinatal morbidity and mortality from this condition. The present study defined the range for the oral glucose tolerance test (oGTT) in 2578 pregnancies. After exclusion of abnormal results 822 randomized patients were used to define normal values for fructosamine, HbA1c, insulin, glucose and C-peptide in the maternal serum; insulin, glucose and fructosamine in the amniotic fluid; and insulin, glucose, C peptide and fructosamine in the cord blood. PMID- 2256716 TI - Response of human endometrium and ovarian carcinoma cell-lines to photodynamic therapy. AB - The response of the human gynecological carcinoma cell-lines HEC-1-A (endometrial carcinoma) and OvCar-3 (ovarian carcinoma) to photodynamic therapy in vitro was examined. The porphyrin compound Photosan III (Ph III) was used for photosensitization of the cells after incubation times of 24 h (HEC-1-A) and 48 h (HEC-1-A and OvCar-3). The Ph III doses varied from 0-10 micrograms/ml medium. Irradiation was performed with laser light at 630 nm. Irradiation doses up to 20 J/cm2 were applied at an irradiance of 40-100 mW/cm2. Cell vitality of the untreated control groups and of the therapy group was determined 48 h after irradiation, using the trypan blue exclusion test. The experimental results show that treatment of OvCar-3 cells with 10 J/cm2 resulted in a decrease in vitality dependent on photosensitizer dose (0-5 micrograms/ml, 48 h incubation time) but independent of the irradiance (40-100 mW/cm2). Complete cell death was observed after application of irradiation doses in the range of 5-20 J/cm2 combined with drug concentrations of 10-2.5 micrograms/ml, at a fixed incubation time of 48 h. HEC-1-A cells did not survive photodynamic therapy with 10 J/cm2 after incubation with 5 micrograms/ml for 48 h. After a shorter incubation time of 24 h, 10 micrograms/ml Ph III was necessary for the same effect. There was a maximum decrease in cell vitality when measured 48 h after irradiation. This was not improved at 72 h. PMID- 2256717 TI - Indications for radioisotope bone scanning in staging of cervical cancer. AB - The total of 160 patients with newly diagnosed invasive cancer of the cervix had whole body radioisotope bone scanning during staging of their disease. 51 patients had cancer of the cervix stage I, 63 had stage II, 34 stage III and 12 stage IV (FIGO). Only in 8 of 160 patients did the bone scans indicate possible metastases and this was confirmed by X-ray examination in only one patient with stage IV disease and liver metastases. We conclude that patients with stage I and stage II carcinoma of the cervix do not need to have bone scans. PMID- 2256718 TI - Vaginosonography and its diagnostic value in patients with postmenopausal bleeding. AB - Using a transvaginal 240 degrees "panorama" sector scanner (5.0 MHz) we performed a sonographic study in 106 women with postmenopausal bleeding before they had a diagnostic dilatation and curettage. Sonographic findings were classified as (1) normal thin endometrial echo, (2) pathologically thickened echo (i.e. more than 1/3 of the a.-p. diameter of the myometrial wall) and (3) spherical echoes representing myomas. We also looked carefully at the borders of the endometrium. 21 cases could not be included because of no histological specimen was available or because the vagina was too narrow for insertion of the probe. The histological and sonographic results were compared. Of 39 women with pathologically thickened endometrial echoes 12 had invasive carcinomas, 9 hyperplastic endometrium, 16 polyps and 2 had normal atrophic endometrium. In the 46 women with normal endometrial echoes 1 had a carcinoma (confined to the mucosa and obscured by a myoma), 1 had hyperplastic endometrium, 4 had small polyps (size below 5 mm) and 40 had normal atrophic endometrium. PMID- 2256719 TI - DNA analysis, chemoresistance testing and hormone receptor levels as prognostic factors in advanced ovarian carcinoma. AB - Fifty patients with advanced (stage III or IV) ovarian carcinoma were followed-up until the date of their death or their fifth year of survival. Prognostic factors, including those currently in use, as well as ploidy and proliferation, chemoresistance testing and hormone receptor levels of the tumours were analysed for predictive value and independence from each other. In the univariate analysis, only stage, residual tumour, second-look status, chemoresistance, ploidy and proliferation were significantly correlated with survival. After being tested in a multivariate Cox regression model, however, only the results of chemoresistance testing at initiation of therapy, and second-look status at a later point, retained prognostic significance. Within the group of patients with a positive second-look, i.e., with the worst prognosis, the chemoresistance test was still able to discriminate between two subgroups with significantly different survival. PMID- 2256721 TI - Nursing and technology ... nurses and technicians. PMID- 2256722 TI - Stress, coping, and quality of life in adult kidney transplant recipients. AB - The purpose of this study was to identify specific stressors and coping strategies identified by adult kidney transplant recipients in the first 6 months after transplantation. Quality of life was used as the outcome measure. Subscales were rationally constructed based on literature review and logic for both the stress and coping scales. Health-related items were identified as most stressful including uncertainty about whether the transplant will be a success and concern about risk of infections and/or viruses. Work-related items were least stressful. Strongly endorsed coping strategies included items on the Distancing/detachment and Self-control/accepting responsibility subscales. Quality of life scores were significantly higher after the transplant than before. Total stress was the important predictor of quality of life before transplant. Both total stress and total coping were important predictors of quality of life after transplant. The expanded transplant nursing role provides an opportunity to identify stressors and suggest appropriate coping strategies early in the transplant experience. PMID- 2256720 TI - Ritodrine-induced agranulocytosis. PMID- 2256724 TI - Posttransplant quality of life expectations. AB - This descriptive exploratory study with 57 renal transplant recipients employed a structured interview guide to determine where patients heard about transplantation, what knowledge they had about transplantation, and why they chose to have a transplant. Nearly half the patients heard about transplantation from their physician and a fourth from their dialysis nurse. Patients had little comprehensive knowledge about transplantation, and most patients indicated transplantation was chosen merely to get off dialysis. The interview also sought to determine what expectations transplant recipients and their nurses had for the patients post-transplant quality of life. Both patients and nurses viewed transplantation as creating many more favorable quality of life changes as opposed to negative changes, however, the nurses anticipated significantly more positive as well as negative changes than did the patients. PMID- 2256723 TI - Stress, coping, and quality of life in family members of kidney transplant recipients. AB - This study explored specific stressors and identified coping strategies used by family members of kidney transplant recipients in the first 6 months following transplantation. Quality of life was also briefly examined as the outcome measure. Health-related items were identified as most stressful, and work-related items as least stressful. Self-controlling and problem-solving coping strategies were most frequently used, and escape/avoidance strategies were least used. Findings from this study have implications for development of specific teaching plans for transplant recipient families, as well as for collaborative team exploration of family stress and coping. PMID- 2256725 TI - Stressors in renal transplant recipients at six weeks after transplant. AB - The purpose of this study is to identify stressors that renal transplant recipients report experiencing 6 weeks posttransplantation and compare them with stressors reported by Hayward et al. (1989). The sample consists of 48 adult renal transplant recipients. Stressors are measured by the Kidney Transplant Recipient Stress Scale. The most stressful item identified is the possibility of repeated hospitalizations, different from the Hayward Study in which possibility of rejection was the most frequently reported stressor. Nurses can use this information to better understand the stressors related to the renal transplant experience and to then develop appropriate interventions that can enhance clients' self-care actions. PMID- 2256726 TI - Medical case review of the quality and appropriateness of ESRD services. AB - The Health Care Financing Administration (HCFA) has developed procedures and criteria now being used by the End Stage Renal Disease Network organizations in the review of facilities and providers to assure the quality and appropriateness of care provided to ESRD patients. This review was mandated by the Omnibus Budget Reconciliation Act (OBRA) of 1986. The consistent application of defined quality review criteria screens throughout the country will provide the foundation for a new era of quality care. PMID- 2256727 TI - Nursing management of the pregnant hemodialysis patient. AB - Pregnancy is an uncommon occurrence in the end stage renal disease (ESRD) patient population and more so in the patient on chronic hemodialysis therapy. The management of the pregnant hemodialysis patient covers a wide spectrum of concerns. Many resources must be used to deliver safe, quality care to the patient. The knowledge gained from our experience in caring for a pregnant hemodialysis patient will benefit the nephrology nursing community. With the advent of erythropoietin, the number of pregnant ESRD patients may grow, and the demand for knowledge on how to care for these patients will also become increasingly evident. PMID- 2256728 TI - Transfusion therapy: associated risks and alternative approaches. AB - Transfusion therapy has been the mainstay for treating the anemia of end-stage renal disease (ESRD). Recently, several factors, including the awareness of associated risks, especially the transmission of blood-borne diseases and the transient treatment effect with regard to reversal of anemic symptoms, have caused a reassessment of transfusion therapy. Recombinant human erythropoietin (epoetin) has emerged as the alternative treatment, capable of sustained reversal of anemia without the associated risks of transfusions. The result of epoetin therapy has been marked improvement in the quality of life of ESRD patients. However, the advent of this therapy has also changed the nurse's role in caring for ESRD patients, as new medical management issues are identified and supportive care is tailored to the individual patient. PMID- 2256729 TI - Nephrology nursing consult: case study. Amyloidosis: management difficulties associated with a progressive multisystem disease. PMID- 2256730 TI - Reuse of high flux dialyzers. PMID- 2256732 TI - The role of ANNA's president: an interview with Barbara Bednar. PMID- 2256731 TI - Case management of the anemic patient. Epoetin alfa: focus on inflammation and infection. AB - Nursing management of anemic dialysis patients requires a thorough understanding of the conditions that can potentially affect erythropoiesis. Erythropoietin deficiency has been documented as the primary cause of the anemia of uremia, and Epoetin alfa has proven to be an effective therapy for correcting this condition. However, other etiologies, independent of the uremic process, can also contribute to anemia in these patients and lead to a diminished response to Epoetin alfa. Iron deficiency and blood loss, for example, are well-documented etiologies that can hinder erythropoiesis and diminish the response to Epoetin alfa (Van Wyck, 1989). Another etiology still under investigation is the potential effect of infection or inflammation on the response to Epoetin alfa. This article examines the anemia of infection and inflammation and the potential effect on response to Epoetin alfa. PMID- 2256733 TI - Skeletal palaeopathology and the rheumatic diseases: where are we now? PMID- 2256734 TI - Enhanced expression of the heat shock protein gene in peripheral blood mononuclear cells of patients with active systemic lupus erythematosus. AB - The spontaneous increase in the transcription of the heat shock protein (hsp 70) gene in peripheral blood mononuclear cells of patients with active systemic lupus erythematosus (SLE) is shown by nuclear run on transcription assay. The transcription of hsp 70 gene in the peripheral blood mononuclear cells of five patients with active SLE was more than 10 times greater than that in five normal healthy subjects or three patients with bronchial asthma as controls. This suggests that heat shock proteins may be produced during an active immune response in patients with active SLE and play a part in a change related to lupus of the essential intracellular functions of peripheral blood mononuclear cells. PMID- 2256735 TI - Osteoarticular brucellosis in children. AB - The findings in 40 children (24 female, 16 male) with osteoarticular complications of brucellosis are presented. Raw milk was the main source of infection. Most patients had acute onset of fever, arthralgia, and myalgia. Arthritis was the presenting symptom in all patients, of whom two also had osteomyelitis. Arthritis was monoarticular in 28 (70%) of 40 cases with predilection for large weight-bearing joints. Spine and small joints were spared. Brucella melitensis was detected in 23/31 (74%) cases. Mild anaemia, leucopenia, increased liver enzymes, positive acute phase reactants, and low titres of autoantibodies were prominent non-specific laboratory findings. Bone scintigraphy was more helpful than conventional radiography in detecting hip and sacroiliac joint disease. Treatment with a combination of antibiotics for six weeks or more resulted in a cure rate of 92.5%. Early recognition of infection, prolonged treatment, and long term follow up should improve the outcome of patients. PMID- 2256736 TI - Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor. AB - The clinical and biochemical correlations with joint damage progression over two years in a consecutive group of 68 patients with rheumatoid arthritis with disease duration of less than two years are reported. Joint damage was assessed with Larsen's severity scale and a measure of change in progression rate constructed. Initial haemoglobin concentration, Ritchie index, and Waaler-Rose titre in combination accounted for one third of the variance in joint damage progression. Rheumatoid factor (RF) concentrations were followed with enzyme linked immunosorbent assays (ELISAs) for IgG RF, IgA RF, and IgM RF. The RF concentrations, except IgG RF, decreased with time; significant correlations between RFs and disease activity were few and barely clinically useful. After two years IgG RF correlated significantly with a radiological score if early non erosive changes were omitted. All RFs tended to correlate better with this radiological score at all three observation points. Analyses of the change in progression rate indicated a time delay between development of radiographic changes and increase of IgG RF. These results suggest an indirect relation between RFs and joint damage. Clinical and biochemical improvements in early RA occur despite joint damage progression, and conventional markers have insufficient predictive value. PMID- 2256737 TI - Rheumatoid factors specific for active rheumatoid arthritis. AB - To measure rheumatoid factors specific for patients with rheumatoid arthritis an enzyme linked immunosorbent assay (ELISA) was developed to measure rheumatoid factors in human serum that bind a cross-reactive determinant shared on human and other mammalian IgG. Rheumatoid factors that cross link human IgG and sheep IgG in a double binding ELISA were almost completely specific (greater than 99%) for rheumatoid arthritis in assays of 108 sera from patients with rheumatoid arthritis compared with 231 sera from patients with other connective tissue diseases and 365 sera from healthy subjects and patients without these diseases. Moreover, positive tests occurred primarily in patients with active arthritis (r = 0.68). In contrast, these rheumatoid factor autoantibodies were not detected in sera from most of the patients with other autoimmune diseases, including patients with systemic lupus erythematosus. These results show that rheumatoid factors identified in human sera by the double binding test are specific for active rheumatoid arthritis. PMID- 2256738 TI - Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. AB - An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years' duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 'disease activity score'. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists' decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms. PMID- 2256739 TI - Relation between chest expansion, pulmonary function, and exercise tolerance in patients with ankylosing spondylitis. AB - Thirty three patients with definite ankylosing spondylitis (AS) were examined to establish the relation between restriction of chest expansion, limitation of lung function, and working capacity or exercise tolerance. As in previous studies there was a significant association between chest expansion and lung vital capacity. There was also a significant association between vital capacity and exercise tolerance as measured by a subject's maximum oxygen capacity (VO2max). Both vital capacity and VO2max were expressed as a percentage of predicted normal values using patients' height before disease. In this study chest expansion did not have a significant effect on exercise tolerance. The results suggested that patients who took a modest amount of exercise regularly could maintain a satisfactory work capacity despite very restricted spinal and chest wall mobility. It is recommended that greater emphasis should be given to encouraging patients with AS to maintain cardiorespiratory fitness as well as spinal mobility. PMID- 2256740 TI - 5-fluorouracil in the treatment of scleroderma: a randomised, double blind, placebo controlled international collaborative study. AB - A six month controlled study of 5-fluorouracil in the treatment of scleroderma showed a modest benefit in skin scores, Raynaud's phenomenon, and patients' global assessment. Visceral organ and hand function were unaffected. Mild to moderate toxicity was common in the 5-fluorouracil treated patients but usually responded to dose reduction. Two patients receiving 5-fluorouracil died from causes seemingly unrelated to treatment. Significant clinical improvement in scleroderma was not noted in the first six months of treatment with 5 fluorouracil. PMID- 2256741 TI - Role of bone scintigraphy in the early diagnosis of discitis. AB - Nine cases of recorded discitis are presented, in which scintigraphy played an important part in the diagnosis. The patients (five men (aged 21-75 years) and four women (aged 40-73 years)) had a history of back pain varying in duration from two days to three months. Final diagnosis was confirmed microbiologically (seven patients) or radiographically (two patients). Bone scintigraphy was a valuable diagnostic procedure for discitis with earlier detection than plain radiography in three patients and similar initial detection to that of third generation computed tomography. Single photon emission computed tomographic imaging increased diagnostic confidence by indicating the involvement of the adjacent vertebral bodies rather than of the pedicles or spinous processes. PMID- 2256742 TI - Raynaud's phenomenon and positive antinuclear antibodies in a malignancy. AB - Both Raynaud's phenomenon and the presence of antinuclear antibodies are uncommon features of malignant disease and the association of both with a malignancy extremely rare. The case is reported of a 78 year old woman who presented with Raynaud's phenomenon and positive antinuclear antibodies related to adenocarcinoma of unknown primary site. PMID- 2256743 TI - Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation. AB - Autoimmune diseases following silicone or paraffin implantation are rarely encountered complications of plastic surgery. A 42 year old woman is presented who developed clinical and immunological features of systemic lupus erythematosus 11 years after silicone augmentation. After explanation antinuclear antibody titres decreased from 1/1280 to 1/160, C4 complement fraction and the previously raised angiotensin converting enzyme normalised in step with clinical improvement. It is important that plastic surgeons and rheumatologists should be aware of this possible association. PMID- 2256744 TI - Recurrent cerebral infarction and the antiphospholipid syndrome: effect of intravenous gammaglobulin in a patient with systemic lupus erythematosus. AB - A 23 year old woman with systemic lupus erythematosus and antiphospholipid syndrome developed severe thrombocytopenia (5-10 X 10(9)/l) and cerebral infarction. Treatment with high doses of corticosteroids and cytostatic drugs was not effective. The condition was successfully treated only when three courses of intravenous gammaglobulin at 400 mg/kg daily was added. A clear relation was found between the immunoglobulin infusions and rising platelet counts, whereas an effect on the levels of anticardiolipin antibodies could not be recorded. The findings suggested that the mechanisms responsible may be modification and solubilisation of immune complexes or interference with anticardiolipin binding to platelet membranes, or both. PMID- 2256746 TI - Posterior compartment syndrome following ruptured Baker's cyst. AB - A 35 year old man presented with the sudden onset of left leg pain and swelling. Empirical anticoagulation for presumed deep vein thrombophlebitis was followed by acute worsening of symptoms. On further evaluation the patient was found to have a ruptured Baker's cyst and an acute posterior compartment syndrome. PMID- 2256745 TI - Gout and neurological abnormalities associated with cardiomyopathy in a young man. AB - A 21 year old man with a family history of gout and neurological deficits, developed severe idiopathic congestive cardiomyopathy after a long history of typical gouty attacks and neurological abnormalities. Clinical and laboratory evaluations showed borderline mental retardation, ataxia, sensorineural deafness, marked hyperuricaemia, and excessive uric acid excretion in the presence of impaired renal function. None of the known causes of cardiomyopathy was found. Even though red cell hypoxanthine guanine phosphoribosyltransferase enzyme activity was normal, this case probably represents an inborn error of purine metabolism. The association of cardiomyopathy with gout is very unusual. Previously it has been only once described in a single case. PMID- 2256747 TI - 'Overlap' syndromes. PMID- 2256749 TI - Antenatal administration of aminopropylidene diphosphonate. PMID- 2256750 TI - Fatal acute pyelonephritis following pulsed methylprednisolone for rheumatoid arthritis. PMID- 2256751 TI - Response criteria for slow acting antirheumatic drugs. PMID- 2256748 TI - Hyaluronate in rheumatology and orthopaedics: is there a role? PMID- 2256752 TI - Correlation of iron exchange between the oral iron chelator 1,2-dimethyl-3 hydroxypyrid-4-one(L1) and transferrin and possible antianaemic effects of L1 in rheumatoid arthritis. PMID- 2256753 TI - Habitual knuckle cracking and hand function. PMID- 2256754 TI - Trauma and seronegative spondylarthropathy. PMID- 2256755 TI - Sepsis and tumor necrosis factor--bedfellows that cannot be ignored. PMID- 2256756 TI - Hepatic abscess. Changes in etiology, diagnosis, and management. AB - Most recent reviews of pyogenic hepatic abscess emphasize percutaneous versus open surgical management and devote little time to studying the etiology or the clinical condition of the patient. In this study a detailed review was performed with a computerized analysis of multiple clinical parameters in 73 patients treated for pyogenic hepatic abscess during a 17-year period. The mean age of the patients was 55 years and 38 of them (52%) were male. The mortality rate was comparable for solitary (17%) and multiple (23%) abscesses. The likelihood of death was higher with antibiotic treatment alone (45%) or percutaneous treatment (25%) than with surgical treatment (9.5%). The primary determinant of outcome, however, was the underlying disease, i.e., malignancy or an immunocompromised patient, rather than solitary versus multiple abscesses. In addition the incidence of hepatic abscess seen at this center has doubled from the first half to the second half of the review, reflecting a population of more severely ill patients. It is apparent that in current clinical practice several methods of management are effective, and the choice of therapy should be determined by individualized selection. The principle of timely diagnosis and prompt institution of treatment appropriate to the specific patient remains the standard of care in this potentially grave disease. PMID- 2256758 TI - The effect of ambulation on recovery from postoperative ileus. AB - To determine whether ambulation hastens recovery from ileus following laparotomy, 34 patients were studied, 10 of whom followed an ambulatory regimen beginning on postoperative day 1 (group A). The other 24 patients (group C) did not become ambulatory until postoperative day 4. All patients underwent placement of seromuscular bipolar recording electrodes on the Roux limb, if present, stomach, jejunum, and colon at laparotomy. Group A was recorded before and after ambulation so comparisons could be made to determine if ambulation had an acute effect on myoelectric activity. Group A preambulation and group C recordings were compared to judge whether there was an over-all effect of ambulation on myoelectric recovery. No effect on slow wave frequency or percentage of slow waves with associated spike potentials was noted acutely or overall in the stomach, colon, or jejunum in continuity with the duodenal pacemaker. Transient increases in phase II spike activity in patients having a Roux limb and their jejunum distal to the enteroenterostomy were noted on postoperative days 1 to 2, but these differences resolved by postoperative days 3 or 4. The data suggest that ambulation as a means to help resolve postoperative ileus and its accompanying cramps and bloating may be more perceived than real. PMID- 2256757 TI - The effects of tumor necrosis factor on intestinal structure and metabolism. AB - Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study. PMID- 2256759 TI - Efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome. AB - The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome. In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion. On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected. An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls. During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin. Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo. Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides. These changes were associated with complete ablation of diarrhea (p less than 0.001). Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping. Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05). Chronic daily treatment with octreotide acetate resulted in minimal side effects. These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period. In addition most patients were able to resume employment. The long-acting somatostatin analog, octreotide acetate, is highly effective in preventing the development of symptoms of severe dumping syndrome, both vasomotor and gastrointestinal. PMID- 2256760 TI - Reperfusion inhibits elevated splanchnic prostanoid production after hemorrhagic shock. AB - The effect of reperfusion following hemorrhagic shock on splanchnic prostanoid release was studied. Anesthetized male rats were bled to a mean arterial blood pressure of 30 mmHg for 30 minutes and either killed or treated with shed blood for 60 minutes and then killed. The superior mesenteric arterial bed was cannulated and perfused in vitro with oxygenated Krebs. Collected venous effluent (up to 180 minutes) was analyzed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, PGF2 alpha, and thromboxane B2 by radioimmunoassay in shock, shock plus reperfusion, and sham groups. The major prostanoid released was 6-keto-PGF1 alpha and was three times higher in the shock group compared to the sham group (p less than 0.05). Reperfusion of shed blood abolished the increase in 6-keto-PGF1 alpha found in the shock group (p less than 0.05). These data show that the attempt of the rat splanchnic bed to compensate for hemorrhagic shock by increasing release of PGI2 (potent vasodilator) was abolished during reperfusion of blood. PMID- 2256761 TI - Blunt traumatic cardiac rupture. A 5-year experience. AB - Blunt traumatic cardiac rupture is associated with a high rate of mortality. A review of the computerized trauma registry (1983 to 1988) identified 32 patients with this injury (ages 19 to 65 years; mean age, 39.5 years; 21 men and 11 women). Twenty-one patients (65.6%) were injured in vehicular crashes, 3 (9.4%) in pedestrian accidents, 3 (9.4%) in motorcycle accidents; 3 (9.4%) sustained crush injury; 1 (3.1%) was injured by a fall; and 1 (3.1%) was kicked in the chest by a horse. Anatomic injuries included right atrial rupture (13[40.6%]), left atrial rupture (8 [25%]), right ventricular rupture (10[31.3%]), left ventricular rupture (4[12.5%]), and rupture of two cardiac chambers (3 [9.4%]). Diagnosis was made by thoracotomy in all 20 patients presenting in cardiac arrest. In the remaining 12 patients, the diagnosis was established in seven by emergency left anterolateral thoracotomy and in five by subxyphoid pericardial window. Seven of these 12 patients (58.3%) had clinical cardiac tamponade and significant upper torso cyanosis. The mean Injury Severity Score (ISS), Trauma Score (TS), and Glasgow Coma Scale (GCS) score were 33.8, 13.2, and 14.3, respectively, among survivors and 51.5, 8.3, and 7.0 for nonsurvivors. The overall mortality rate was 81.3% (26 of 32 patients), the only survivors being those presenting with vital signs (6 of 12 patients [50%]). All patients with rupture of two cardiac chambers or with ventricular rupture died. The mortality rate from myocardial rupture is very high. Rapid prehospital transportation, a high index of suspicion, and prompt surgical intervention contribute to survival in these patients. PMID- 2256763 TI - The risk of large bowel cancer after partial gastrectomy for benign ulcer disease. AB - The relative risk (standardized incidence ratio [SIR] for colorectal cancer after partial gastrectomy for ulcer disease was examined in a population-based cohort comprising 6459 patients operated during 1950 to 1958. Follow-up through 1983 revealed 131 cases of colorectal cancer versus 150.3 expected cases (SIR = 0.87; 95% confidence limits 0.73, 1.03). The relative risk was decreased during the first 19 years of follow-up (SIR = 0.75; 0.58, 0.96) and close to equal thereafter (SIR = 1.02; 0.79, 1.29). Sex, age at operation, type of operation, and diagnosis at operation (stomach or duodenal ulcer) did not affect the relative risk significantly. Confounding by socioeconomic status is one conceivable explanation for the decreased relative risk during the first years of follow-up, whereas the increasing risk with longer duration of follow-up might be a consequence of the surgical procedure itself. PMID- 2256762 TI - Treatment of patients with aortic dissection presenting with peripheral vascular complications. AB - The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients. PMID- 2256764 TI - The role of inhalation injury in burn trauma. A Canadian experience. AB - From 1977 to 1987, 1705 thermally injured patients were admitted to the Firefighters' Burn Center at the University of Alberta Hospitals. Thirteen hundred forty-four were male (78.8%) and 361 were female (21.2%), with a mean total burn surface area (TBSA) of 15.1 (SEM +/- 0.4%) and a range of 1% to 99% TBSA. Sixteen hundred thirty-five patients survived to be discharged from hospital, with an overall survival rate of 95.9%. One hundred twenty-four burn patients (7.3%) suffered concomitant inhalation injury diagnosed by bronchoscopy. Patients with inhalation injury suffered from larger TBSA (39.7% +/- 2.8% versus 12.2% +/- 0.3%; p less than 0.01) than those without inhalation injury. Inhalation injury increased the number of deaths from burn injury (34.7% versus 1.7%; p less than 0.01) independent of age and TBSA. Inhalation injury was associated with a threefold prolongation of hospital stay (23.7 +/- 0.7 versus 74.4 +/- 6.2 days; p less than 0.01) and was independent of age and TBSA. Multifactorial probit analysis was performed for both inhalation- and noninhalation-injured burned patients to allow TBSA and age adjusted rates of mortality for the burn population presented. The maximum detrimental effects of inhalation injury in burn patient outcome occurred when it coexisted with moderate (15% to 29% TBSA) to large (30% to 69% TBSA) thermal injuries. These data demonstrate that inhalation injury is an important comorbid factor in burn injury that increases the number of deaths substantially. Most importantly such injuries also independently prolong the duration of hospitalization in a highly unpredictable fashion as compared to patients with cutaneous burns only. As such our data illustrate the extreme importance of inhalation injury as a comorbid factor following thermal injury and reveal the present limitations for accurate quantification of the magnitude of respiratory tract injury accompanying thermal trauma. PMID- 2256765 TI - Involvement of thromboxane and neutrophils in multiple-system organ edema with interleukin-2. AB - Interleukin-2 (IL-2) produces toxicity characterized by generalized edema within 24 hours. This study tests whether the rate of IL-2 administration modulates the onset of edema and examines thromboxane (Tx) and neutrophils as possible mediators of this event. Recombinant human IL-2, 10(5) U (n = 7), 10(6) U (n = 9), or vehicle (n = 8) were given to anesthetized rats intravenously during a period of 1 hour. At 6 hours edema, as measured by increase in wet to dry weight (w/d) ratio, was present in the heart, liver, and kidney, with 10(5) U IL-2 and in the lung, heart, liver and kidney, with 10(6) U IL-2, relative to values with vehicle-infused controls (all p less than 0.05). With a 1-hour infusion of 10(6) U IL-2, there was an increase in plasma thromboxane (Tx)B2 level to 1290 +/- 245 pg/mL, higher than 481 +/- 93 pg/mL in control rats (p less than 0.05); lung polymorphonuclear leukocyte (PMN) sequestration of 53 +/- 7 PMN/10 higher-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05); and increased bronchoalveolar lavage (BAL) fluid protein concentration of 1970 +/- 210 micrograms/mL relative to 460 micrograms/mL in controls (p less than 0.05). When 10(6) U IL-2 was given as a 1-minute intravenous bolus (n = 9), edema was not demonstrated, plasma TxB2 levels were similar to controls, there was no leukosequestration, and BAL protein levels were normal. These data indicate that a constant infusion but not the rapid bolus administration of IL-2 produces in rats multiple-system organ edema, increased plasma TxB2, sequestration of PMNs, and microvascular permeability. These findings may explain the early toxicity seen in patients given high-dose IL-2 in cancer treatment. PMID- 2256766 TI - A night-time role of the oviposition site of the mosquito, Aedes aegypti (L.) (Diptera: Culicidae). AB - Experimental observations taken outdoors in Trinidad are consistent with the assumption that the oviposition site is used by some gravid female Aedes aegypti as a nocturnal resting site prior to their laying eggs in it the next morning: the morning wave of oviposition of the typically bimodal diel periodicity was missing whenever an oviposition site was closed throughout the previous night. The diel pattern of oviposition did not differ significantly in sites at, and four feet above, ground level. PMID- 2256767 TI - Malaria in Nigeria: a revisit. AB - The frequency of asymptomatic malaria parasitaemia was investigated in rural and urban school-children aged six to 12 years in southwestern Nigeria between January 1987 and October 1988. Asymptomatic parasitaemia was detected in the rural school-children all year round with the lowest parasite rate in January and the highest in July, corresponding to the mid-dry and wet seasons respectively. Asymptomatic parasitaemia was also common amongst urban school-children, but the frequency was lower than in the rural children. Parasite density was less than or equal to 1000 microliters-1 in 42% of parasite-positive asymptomatic children and was greater than 10,000 microliters-1 in only 20% of them. Mass treatment with chloroquine, to which the parasites were fully sensitive, was followed by the same rate of re-infection in the parasite-positive and parasite-negative groups. Of 7713 patients clinically diagnosed as having malaria 4425 were found to have parasitologically-proven malaria, and of these 4239 had pure Plasmodium falciparum malaria. Of the patients with falciparum malaria only 4.6% were below the age of one year. In 47% the parasite count was less than or equal to 1000 microliters-1, and it was over 10,000 microliters-1 in 37% and over 250,000 microliters-1 in 16%. There was no significant difference between the asymptomatic children and the acutely ill patients in the percentage with parasite densities less than or equal to 1000 microliters-1, but the percentage with parasite densities greater than 10,000 microliters-1 was significantly greater in the acute malaria patients than in those with asymptomatic parasitaemia. PMID- 2256768 TI - Treatment of Echinococcus granulosus hydatid disease with albendazole. AB - The authors report their personal experience of the treatment of 50 patients with hydatid cysts of different localization with 10-12 mg Albendazole per kg per day for three months without intervals. During the treatment patients were submitted to careful clinical, biochemical, radiological and immunological controls. In all 105 hydatid cysts were observed, and the follow-up periods ranged from six to 42 months. The side effects were not severe. Four patients were considered healed, 31 improved, and 11 showed no change. Three patients relapsed after the end of the therapy, and were treated with a further cycle of Albendazole at the same dose rates, with good effect. The observed results are encouraging, and most of the patients did not require surgery. PMID- 2256769 TI - Echinococcosis in Libya. III. Further studies on the prevalence of Echinococcus granulosus in dogs. AB - Of 92 dogs examined for Echinococcus granulosus at five sites in Libya from April 1985 to September 1988 33 (35.9%) were infected, the prevalences ranging from 60% (Zawiyah) and 52.0% (Tripoli) in the north-west, to 28.6% (Benghazi) and 28.5% (Darna) in the north-east. None of eight dogs at Al-Kufra, in the south-eastern desert, were infected. Twenty dogs each had two to 200 worms, nine had 201-1000 worms and four each had over 1000 worms (one dog in Tripoli had 17,120 worms). Most infections were seen in dogs aged three to four years; 45.4% of bitches and 35.4% of males were infected. PMID- 2256770 TI - Echinococcosis in Libya. IV. Prevalence of hydatidosis (Echinococcus granulosus) in goats, cattle and camels. AB - During a survey of 14 Libyan abattoirs in 1985-1987 the carcasses of 4316 locally bred goats, cattle and camels were inspected for cysts of Echinococcus granulosus. Of 2295 goats, 35 adults (1.5%) had cysts; no kids were infected. Thirty-one adult goats had infected livers, 28 had lung infections, and four each had cysts in their kidneys and spleens. Most (59.7%) of the infections were light, with medium infections in 31.3% and heavy infections in 8.9%; 85.7% of the cysts in the lungs and 38.7% of those in the livers were fertile; three of the four kidney infections and two of the four spleen infections were fertile. Of the 1023 cattle carcasses, mild infections with E. granulosus were seen in 55 (5.4%); all the cysts were sterile and confined to the liver. Of 998 camels, 358 (35.9%) had hydatid cysts. These involved the lungs in 96.9%, either as the sole site (74.3%) or jointly with the liver (22.6%). Lung cysts (57.6%) and liver cysts (41.2%) were fertile. PMID- 2256771 TI - Comparison of the susceptibility to deltamethrin of female Glossina morsitans morsitans Westwood, 1850 (Diptera: Glossinidae) uninfected and infected with Trypanosoma (Nannomonas) congolense Broden, 1904 (Kinetoplastida, Trypanosomatidae). AB - The susceptibility of pregnant female Glossina morsitans morsitans Westwood, 1850 infected with Trypanosoma (Nannomonas) congolense Broden, 1904 to deltamethrin, a synthetic pyrethroid insecticide, was compared to that of pregnant uninfected females. The results showed that infected flies have a significantly higher mortality rate than uninfected ones, and have a reduced longevity compared with uninfected control flies. These experiments suggest that the effects of trypanosome infection on Glossina should be further evaluated. PMID- 2256772 TI - The onchocerciasis focus at Kinsuka/Kinshasa (Republic of Zaire) in 1985. II. Parasitological and clinical aspects. AB - Since the antivectorial control in 1948, the parasitological and clinical aspects of the onchocerciasis focus at Kinsuka/Kinshasa have not been studied further until now. The population examined was selected for its daily contact with the vector. It constituted 143 adults, including fishermen, stonebreakers and women cultivators, and 26 children aged from 10 to 16 years. People were subjected to an ophthalmological examination as well as to an investigation for Onchocerca volvulus microfilariae. Adults were examined for the presence of nodules as well as for dermal and lymphatic manifestations of onchocerciasis. The microfilaria carrier rate (MfCR) was 59.2%. The mean microfilaria density (MfD) was 9.7 mf mg 1. Only 20% of the adults presented with small onchocercal nodules. Cutaneous lesions were mild. Lymphatic complications such as adenolymphocele, hydrocele and elephantiasis of the lower limbs were observed in 18% of the adults. No one was blind from onchocerciasis, although nine patients of 60 years or over had lost the use of one eye. Punctate keratitis occurred commonly in young people. Ocular lesions, except for punctate keratitis, developed progressively after 55 years and they became worse with the degree of infection, age and length of stay. Hyperendemic and insufferable in 1940, onchocerciasis has become, in 1985, hypoendemic and no longer a public health problem. One could deduce that a situation similar to that in Kinsuka may occur within 30 years in other foci which are today hyperendemic and where prophylaxis has been started. PMID- 2256774 TI - Leprosy in Kuwait: an epidemiological study of new cases. AB - The latency of infection in leprosy is long so that new cases may present several years after emigration from endemic areas. This is of concern to the health authorities in Kuwait, since there is a sizeable immigrant population. An epidemiological study of new cases was, therefore, conducted to assess the extent of the leprosy problem. A total of 121 (99 male, 22 female) consecutive new leprosy patients were diagnosed nationwide over a six-year period (1983-1988). Over 95% of the patients were foreign born, emphasizing that the problem in Kuwait is mainly a reflection of immigration patterns. There were 74 cases of Asio-Indian origin, 13 Oriental and 34 Arab (including two Kuwaiti). This represents a respective mean incidence of the disease in Kuwaitis and other nationalities of 0.49 and 18.92 per 100,000 per year. Polar lepromatous (LL) leprosy was the most frequent type in the Arab group (44.1%) and polar tuberculoid (TT) the most frequent in the Asio-Indian group (37.8%). LL and borderline lepromatous (BL) types of leprosy were significantly more frequent in patients over 45-years-old and in females (P less than 0.05), contributing to the higher rate of LL in the Arab cases. The mean lag time from symptoms onset to presentation to doctor was 9.4 (range 0-192) months, with lepromatous cases tending to present later than other types. The longest lag times occurred in Arab women with LL, suggesting that cultural influences may delay presentation of leprosy. The mean interval from presentation to diagnosis was 4.1 weeks. The mean latency from entry into Kuwait to diagnosis was 44.7 (range 0-180) months; which stresses the need for physicians to remain vigilant in considering leprosy, especially in any patient with dermatological, neurological or ophthalmic manifestations of disease. PMID- 2256773 TI - Ivermectin and coagulation: an in vitro study. AB - The prothrombin time, partial thromboplastin time with kaolin, and thrombin clotting time of plasma derived from healthy human volunteers were unaltered after in vitro addition of therapeutic concentrations (20-90 ng ml-1) of ivermectin. No difference in these coagulation tests, relative to untreated controls, was observed after 12 hours' incubation with the drug. PMID- 2256775 TI - The effect of the pH of various dairy products on the survival and growth of Brucella melitensis. AB - In this study we report the effect of the pH of various dairy products on the survival and growth of Brucella melitensis. The growth patterns of B. melitensis in broth media at different pHs (ranging between 3 and 9) were studied for up to four weeks, to standardize the growth of the organism at each pH. These growth patterns were compared with those of the same organism growing in different dairy products [milk, soft cheese, yoghurt, and buttermilk (shaneena)] under the same growth conditions. This showed that B. melitensis could survive for more than four weeks in broth at a pH of greater than or equal to 5.5, was inhibited in less than three weeks at pH 5 and in one day at pH 4, but could not survive in a pH of less than 4. In dairy products there was a marked drop in the total viable count, and the organism could not be detected after short periods of time. After 72 hours B. melitensis could be detected only in soft cheese, but it was not detectable in any of the dairy products tested after 96 hours. Thus, this study has shown that the survival of B. melitensis in the different dairy products was inversely proportional to the pH of the product. PMID- 2256776 TI - Studies of total and high density lipoprotein cholesterol in childhood malaria: a preliminary study. PMID- 2256778 TI - Sero-epidemiological study of human hydatid disease in Libya using finger prick blood samples. PMID- 2256777 TI - Anti-RESA (Pf 155) antibodies in malaria patients from Para and Rondonia, Brazil. PMID- 2256779 TI - Nickel availability and urease expression in Proteus mirabilis. AB - Cells of Proteus mirabilis, previously grown in nutrient broth (NB), exhibited an increase in urease activity during subsequent incubation in mineral medium even when protein biosynthesis was inhibited. During growth in NB, degradation of amino acids obviously led to the formation of nickel-complexing metabolites, and nickel ions were therefore unavailable for maximal expression of enzymatically active urease; this inhibition of urease biosynthesis was overcome by the addition of nickel to the growth medium, and also by added glucose. Experiments concerning the incorporation of radioactive nickel into urease finally indicated that the observed increase in urease activity was caused by posttranslational insertion of nickel into performed apo-urease. PMID- 2256780 TI - Repression of toxin production by tryptophan in Clostridium botulinum type E. AB - Of the seven amino acids required by Clostridium botulinum type E, tryptophan is the most essential and may provide the cell with nitrogen. The addition of excess tryptophan (10-20 mM) or other nitrogenous nutrients to minimal growth medium markedly decreased toxin formation but did not affect growth in C. botulinum type E. On the other hand, the addition of an enzymatic digest of casein (NZ Case) stimulated toxin formation and overcame repression by tryptophan. Immunoblots of proteins in culture fluids using antibodies to type E toxin indicated that tryptophan-repressed cultures produced less neurotoxin protein. Inhibitors of neurotoxin did not accumulate in cultures grown in minimal medium supplemented with high tryptophan. The results suggest that tryptophan availability in foods or in the intestine may be important for toxin formation by C. botulinum type E. PMID- 2256781 TI - Glutathione-gated K+ channels of Escherichia coli carry out K+ efflux controlled by the redox state of the cell. AB - The kinetics of K+ efflux across the membranes of i) wild-type Escherichia coli poisoned by the thiol reagent N-ethylmaleimide, ii) K+ retention mutants and iii) glutathione-deficient mutants, have revealed a common "K+ leaky phenotype"; it is characterized by a very high rate of K+ efflux. The results suggest that the products of kefB and kefC genes could encode two K+ channels, both gated by glutathione. The possible function of these K+ channels seems to be a K+ exit controlled by the redox state of the cell; indeed, it can be inferred from the effects of several oxidants and reductants that turning on and off of the K+ efflux mediated by the channels can be correlated with the redox state of glutathione. PMID- 2256782 TI - Catabolism of 3-hydroxybenzoate by the gentisate pathway in Klebsiella pneumoniae M5a1. AB - Growth of Klebsiella pneumoniae M5a1 on 3-hydroxybenzoate leads to the induction of 3-hydroxybenzoate monooxygenase, 2,5-dihydroxybenzoate dioxygenase, maleylpyruvate isomerase and fumaryl-pyruvate hydrolase. Growth in the presence of 2,5-dihydroxybenzoate also induces all of these enzymes including the 3 hydroxybenzoate monooxygenase which is not required for 2,5-dihydroxybenzoate catabolism. Mutants defective in 3-hydroxybenzoate monooxygenase fail to grow on 3-hydroxybenzoate but grow normally on 2,5-dihydroxybenzoate. Mutants lacking maleylpyruvate isomerase fail to grow on 3-hydroxybenzoate and 2,5 dihydroxybenzoate. Both kinds of mutants grow normally on 3,4-dihydroxybenzoate. Mutants defective in maleylpyruvate isomerase accumulate maleylpyruvate when exposed to 3-hydroxybenzoate and growth is inhibited. Secondary mutants that have additionally lost 3-hydroxybenzoate monooxygenase are no longer inhibited by the presence of 3-hydroxybenzoate. The 3-hydroxybenzoate monooxygenase gene (mhbM) and the maleylpyruvate isomerase gene (mhbI) are 100% co-transducible by P1 phage. PMID- 2256783 TI - Relationship of the luminous bacterial symbiont of the Caribbean flashlight fish, Kryptophanaron alfredi (family Anomalopidae) to other luminous bacteria based on bacterial luciferase (luxA) genes. AB - Flashlight fishes (family Anomalopidae) have light organs that contain luminous bacterial symbionts. Although the symbionts have not yet been successfully cultured, the luciferase genes have been cloned directly from the light organ of the Caribbean species, Kryptophanaron alfredi. The goal of this project was to evaluate the relationship of the symbiont to free-living luminous bacteria by comparison of genes coding for bacterial luciferase (lux genes). Hybridization of a lux AB probe from the Kryptophanaron alfredi symbiont to DNAs from 9 strains (8 species) of luminous bacteria showed that none of the strains tested had lux genes highly similar to the symbiont. The most similar were a group consisting of Vibrio harveyi, Vibrio splendidus and Vibrio orientalis. The nucleotide sequence of the luciferase alpha subunit gene luxA) of the Kryptophanaron alfredi symbiont was determined in order to do a more detailed comparison with published luxA sequences from Vibrio harveyi, Vibrio fischeri and Photobacterium leiognathi. The hybridization results, sequence comparisons and the mol% G + C of the Kryptophanaron alfredi symbiont luxA gene suggest that the symbiont may be considered as a new species of luminous Vibrio related to Vibrio harveyi. PMID- 2256784 TI - Genetic instability in Streptomyces niveus plasmid pSN2: in vivo formation of deletion derivatives. AB - A plasmid designated pSN2 (molecular size 32.0 kb) was isolated from the wild type of Streptomyces niveus ATCC 19793. To permit phenotypic identification of pSN2 the 1.9 kb BclI fragment was replaced in vitro by the 1.1 kb BclI fragment of pIJ702 carrying the thiostrepton resistance (tsr) gene to form the plasmid pSN3. pSN3 transforms S. lividans to thiostrepton resistance at high frequency and is stably maintained. However, when used to transform S. niveus pSN3 was unstable and produced a 5.5 kb thiostrepton resistant deletion derivative pLG5. pLG5 is also stable and expresses thiostrepton resistance in S. lividans but on transformation of S. niveus was unstable and produced a further thiostrepton resistant derivative, pLG10, of 6.5 kb. pLG5 and pLG10 like pSN3 transform S. lividans at high frequency and produce pocks. DNA hybridizations with a probe derived from pLG5 confirm that pLG5 is derived from DNA sequences present on pSN2 and pSN3. PMID- 2256785 TI - [Purulent meningitis in children. Current therapeutic problems]. PMID- 2256786 TI - [Respiratory manifestation of mucoviscidosis. Uncertainties and perspectives]. PMID- 2256787 TI - [Therapeutic management of purulent meningitis in children. Report of 101 cases]. AB - One hundred and one cases of purulent meningitis without any sign of immediate severity have been prospectively treated. Cefotaxime was given until the results of bacteriological tests; when possible, a randomisation separated one group in which cefotaxime was continued and another group in which cefotaxime was replaced by ampicillin. IV treatment was stopped at the 10th day even in cases with persisting fever. All patients less than or equal to 2 years of age were given phenobarbitone. Serious complications consisted of 4 cases of hypoacousia, equally distributed in either therapeutic group of Haemophilus meningitis. No child developed convulsions when receiving phenobarbitone. Late examination of CSF was uncontributive, even in patients with persisting fever. The following simplifications could be proposed in purulent meningitis with usual clinical picture and course: initial treatment with IIIrd generation cephalosporin; substitution by ampicillin or amoxicillin as soon as bacteriological tests make it possible; discontinuation of IV treatment by the 10th day maximum, without CSF control; prevention of convulsions in young children by phenobarbitone given during the acute stage of meningitis. PMID- 2256788 TI - [Chronic juvenile arthritis with serum antinuclear antibodies. Study of 136 cases]. AB - The charts of 136 patients presenting with juvenile chronic arthritis and antinuclear antibodies were reviewed. Mean age at onset was 3.6 yrs and 120 patients were females. Twenty-one patients presented with the polyarticular type of the disease from onset. Among them, 3 had polyarthritis with presence of rheumatoid factors. During the first year of follow-up, 40% of the pauciarticular forms became polyarticular. They may be subdivided into extended pauciarticular (5 to 9 arthritis = 26% of cases) or polyarticular (greater than 9 arthritis = 15% of cases) forms. The ocular involvement, present in 50 patients, preceded the articular manifestations in 5 cases (for a maximum of 4 years) whereas it followed in 30 cases (maximum delay of 14 years). Inflammatory articular involvement is not always correlated with the risk of ocular involvement. Long term articular prognosis is generally fair. Only 15 children present with clearcut functional handicaps, of whom 4 are requiring the help of a third person. PMID- 2256789 TI - [Gastric acid secretion in children with duodenal ulcer]. AB - Gastric acid secretion was studied in 17 children with primary duodenal ulcer (mean age: 10 yrs 4 mo, rang: 4-16). Eight of the 17 children with primary ulcer had chronic evolution and 10 of them had an affected first degree relative. Basal acid output (BAO) and peak acid output under pentagastrin (PAO) were not significantly different in the 17 children (0.094 +/- 0.085 mmol/kg/hr; 0.483 +/- 0.235 mmol/kg/hr) and in 32 adults with duodenal ulcer (0.073 +/- 0.010 mmol/kg/hr; 0.477 +/- 0.021 mmol/kg/hr). BAO and PAO were not significantly different between children with or without chronic ulcer. The BAO and PAO of children with an affected first degree relative were significantly higher than those of children without (p less than 0.05). This study shows that gastric acid secretions are similar in children and adults with duodenal ulcer. The chronicity of duodenal ulcer in childhood is not associated with increased acid secretion. Gastric acid secretion seems to be higher in children with an affected first degree relative than those without. PMID- 2256790 TI - [Direct diagnosis of predominant mutation delta F508 associated with the mucoviscidosis gene]. AB - The cystic fibrosis locus was mapped on the long arm of the chromosome 7 in 1985. It has recently been cloned and a three base pair deletion has been recognized as the mutation associated with the majority of CF chromosomes (delta F508). CF haplotypes previously defined with tightly associated DNA markers were analysed using PCR (Polymerase Chain Reaction) and allele specific oligonucleotides to determine the presence or absence of this mutation. This mutation was found on 80% of our CF chromosomes and associated predominantly with the B haplotypes. The detection of this mutation is now a major improvement for carrier detection and prenatal diagnosis of the disease. PMID- 2256791 TI - [Fluctuating muscular dystonia. Segawa's syndrome. Value of the treatment with L dopa]. AB - The case of an 8 year-old boy presenting with walking difficulties due to dystonia, peculiar because it was more pronounced during daytime is reported. Improvement with treatment with L-Dopa was dramatic. This diurnal fluctuation and excellent response to L-Dopa suggest the diagnosis of Segawa syndrome. The precise mechanism of the dystonia remains unknown. PMID- 2256792 TI - [Total anomalous infra-cardiac pulmonary venous connection. Value of the color Doppler echocardiography]. AB - A case of total anomalous pulmonary venous connection is described in a newborn. The pulmonary veins join a common trunk entering portal vein below the diaphragm. The pattern of pulmonary venous connections was identified by two-dimensional Doppler color flow-mapping echocardiography. The common pulmonary venous trunk was anastomosed to the left atrium at the age of 3 weeks but the infant died because of pulmonary hypertension and acute renal insufficiency. The Doppler color echocardiography allows a good preoperative evaluation. The spontaneous prognosis being poor, surgical correction is indicated and should be performed early, even for critically ill neonates. Patients who survive to childhood lead active and full lives. PMID- 2256793 TI - [Probable amyotrophic lateral sclerosis. An unusual case. Review of the literature]. AB - A case of neurological disease in a 11 year-old boy is described. The disease began early in life and had recently progressed to paraplegia with pyramidal tract dysfunction, generalized muscle atrophy and numerous fasciculations. The association of pyramidal tract and peripheral dysfunction led to the diagnosis of amyotrophic lateral sclerosis, despite some unusual features. A review of literature data concerning the juvenile and infantile types of the disease is presented, emphasizing the heterogeneity of the disease. PMID- 2256794 TI - [Iconographic rubric. A case of lactobezoar in an infant]. PMID- 2256795 TI - [Allergic provocation test of the nasal mucosa in children]. PMID- 2256796 TI - [Longitudinal study of the feeding of children of 10 months, 2 and 4 years of age]. AB - A longitudinal study of feeding habits in children aged 10 months, 2 years and 4 years was undertaken in 2 health centers for children in the Paris area. The evolution of the feeding of the same children was studied according to age and the nutritional intakes were compared with the recommended dietary allowances of the Centre National de Coordination des Etudes et Recherches sur la Nutrition et l'Alimentation (CNERNA). The results show that there are excesses and insufficiencies common or specific to the 3 ages. High protein and saccharose or sugar supplemented diets were observed at ages 10 months, 2 and 4 years as it was for lipids at age 4 years. Insufficient intakes of iron, essential fatty acids and vitamin E were present at the 3 ages studied. Insufficient zinc and vitamin B1 intakes were found since age 2 years, and insufficient folic acid and vitamin B6 at 4 years. The energy intakes increased between 10 months and 4 years, especially between 10 months and 2 years, where mean increase was twice as important as between 2 and 4 years. Some children received decreasing intakes: 6% ate less at 2 years than at 10 months and 22% less at 4 years than at 2 years. The quantities of aliments taken increased with age except for some aliments such as vegetables, potatoes and fruit. On the basis of the observation of the evolution of children's behavior, one could propose dietary advices, in order to improve the problems described here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256797 TI - [Optimal dose of acetaminophen in children]. AB - Acetaminophen is an antipyretic and analgesic drug frequently prescribed in children. Unlike aspirin, the recommended doses for acetaminophen are different in France (20-30 mg/kg/24 h) and in the USA (65 mg/kg/24 h). The authors reviewed literature data, looking for the scientific basis of these recommendations in children. The antipyretic effect of a 7-20 mg/kg single oral dose was demonstrated versus placebo. A dose-effect relationship was established: 20 mg/kg as a single oral dose was more effective than 10 mg/kg while 5 mg/kg had little antipyretic effect. More than 10 mg/kg were required to keep on average the temperature 1.5 degrees C below the starting point for 6 hours. There was no significant difference regarding the antipyretic effects of a single 10-15 mg/kg dose using suppositories or oral suspension, although there was a greater consistency of response with the oral suspension. There was no significant difference concerning the antipyretic effect between a 10-15 mg/kg acetaminophen oral dose and the same dose of aspirin. The analgesic effect of a single 10-15 mg/kg oral dose was also demonstrated versus placebo in children. Plasma concentrations between 4 and 18 mg/l seem appropriate to obtain an antipyretic effect. Half-life is 1-3.5 h. Based on these data different dose regimens including an initial loading dose have been proposed. The simplest one is as follows: 25 mg/kg loading dose and 12.5 mg/kg every 6 h as maintenance dose. PMID- 2256798 TI - [A case of nosocomial typhoid in a pediatric ward]. PMID- 2256799 TI - [Neonatal Pepper's syndrome with bilateral adrenal tumor]. PMID- 2256800 TI - [Legal defense of children]. PMID- 2256801 TI - [Who is afraid of BCG?]. PMID- 2256803 TI - [Hypertransaminasemia of extrahepatic origin. A way of discovering congenital hypothyroidism]. PMID- 2256802 TI - [Contribution of trace elements in milk formulas for premature infants]. PMID- 2256804 TI - Return to work for persons with traumatic brain injury: a supported employment approach. AB - Supported employment was used to place 41 persons into competitive employment during 30 months. All individuals had experienced severe head injuries; almost 70% of injuries were due to motor vehicle accidents. A mean of seven years had passed since injury for all referred clients, who had been unconscious a mean of 53 days. Only 36% of referred clients had achieved any competitive postinjury employment, compared with 91% of the same group who were competitively employed before injury. A job retention rate of 71% was reported, with most jobs in warehouse, clerical, and service-related occupations. A mean of 291 hours of job coaching was required to place and maintain all clients in supported employment. PMID- 2256806 TI - Impaired awareness of behavioral limitations after traumatic brain injury. AB - Sixty-four traumatically brain injured patients were divided into three groups. Patients in Group I overestimated their behavioral competencies. Patients in Group II showed behavioral ratings similar to relatives' reports concerning behavioral competencies. Patients in Group III underestimated their behavioral competencies. Group I patients had greater evidence of bilateral and multiple site lesions than group II and III patients. Speed of left-hand finger tapping was also worse in Group I than groups II and III, but other standard neuropsychologic test findings failed to separate the groups. Specific brain lesion sites were not related to group membership. Impaired awareness of behavioral limitations after traumatic brain injury may be related to neuropsychologic changes not measured by standard tests. Bilateral impairment of heteromodal cortex may be important to this phenomenon when it exists several months or years postinjury. PMID- 2256805 TI - Functional evaluation of quadriplegic patients using a hand neuroprosthesis. AB - The objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis. The neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles. Data were obtained from telephone interviews, patient records, and videotapes. Twenty-two quadriplegic patients were included in the study; 15 were functional at a C5 spinal cord injury level and seven at a C6 level. The median success rate (ie, the percentage of patients who could complete each activity) across the ten activities was 89% with the hand neuroprosthesis but was only 49% without the hand neuroprosthesis. All patients could perform more tasks when the neuroprosthesis was used, although the relative improvement of C5 patients was larger than that of C6 patients. PMID- 2256807 TI - Maximal exercise testing of mentally retarded adolescents and adults: reliability study. AB - Few data are available regarding maximal exercise testing of mentally retarded individuals. No data are available on the reliability of maximal exercise testing of mentally retarded individuals. The purpose of this study was to determine the reliability of graded exercise testing of mentally retarded adolescents and adults. The testing was conducted at two geographically different centers. At Center A, 14 mentally retarded adolescents (11 boys, three girls) with Down syndrome, who were educable or trainable, were recruited from a nonresidential school. The subjects completed two Balke-Ware treadmill protocols until exhaustion. The treadmill time and heart rate (HR) were recorded. The time between tests was approximately one week. At Center B, 21 mentally retarded adults (14 women, seven men means IQ = 56) were recruited from local workshops and group homes. These subjects completed a treadmill walking protocol, with metabolic measurements, until exhaustion. The time between tests varied from one to four months. At Center A, the subjects achieved a mean treadmill time of 8.72min on test one and 8.84min on test two (means HR = 174 and 175bpm, respectively). The reliability coefficient between the two tests was .94. At Center B, the subjects achieved a mean V0(2)max of 27.2mL.kg-1.min-1 on test one and 26.9mL.kg-1.min-1 on test two. The reliability coefficient was .93. These data show that maximal exercise testing is reliable for these populations of mentally retarded individuals, exhibiting similar values to their nonretarded peers. PMID- 2256808 TI - Cardiac rehabilitation after coronary artery bypass grafting: effects on exercise performance and risk factors. AB - After coronary artery bypass grafting (CABG), 49 nonselected patients followed a cardiac rehabilitation program that included medical follow-up and physical training, both in outpatient groups and on an individual basis at home. The effect of the program on exercise test variables, coronary risk factors, and medication one year after surgery was compared to a nonexercised control group (n = 98). The study group showed less increase in the rate-pressure product, indicating a favorable effect on myocardial oxygen consumption (0.7 +/- 5.4 vs 2.8 +/- 5.6, p less than .05); a lower frequency of angina at exercise testing (6% vs 18%, p less than .01); a reduction in resting systolic and diastolic blood pressure (9/4mmHg, p less than .01); fewer smokers (6% vs 17%, p less than .05); and fewer patients taking long-acting nitrates (0% vs 10.2%, p less than .05). It is suggested, therefore, that an organized cardiac rehabilitation program may be advantageous after CABG. PMID- 2256809 TI - Methodologic and compliance issues in postcoronary bypass surgery subjects. AB - Persons who engage in preventive health behaviors may reduce the progression of coronary artery disease. The immediate objective of this pilot study was to assess adherence to behavioral lifestyle changes in patients after coronary artery bypass graft surgery by analyzing self-reported responses using objective measures. Data on adherence to diet, exercise, and smoking were collected from questionnaires completed by each subject. Carbon monoxide index, serum cholesterol, pre- and postambulatory pulse rates, and pre- and post-stair climbing pulse rates were measured. All tests were conducted before discharge and at a one-month follow-up visit. Analysis of objective data showed a statistically significant reduction in total serum cholesterol, decreased smoking behavior, and increased ambulation from before discharge to one-month follow-up. Analyses showed that self reports of adherence to diet, activity, and smoking cessation were consistent with objective measures in at least 50% of subjects. Serial objective measures provide valuable indicators of patient adherence and assist staff in developing individually tailored patient education. PMID- 2256810 TI - Two unusual gait disturbances: astasia abasia and camptocormia. AB - The physiatrist frequently encounters gait abnormalities in his daily practice. Commonly, there is an obvious organic basis for the disturbance. However, on rare occasions, the gait abnormality is the consequence of a functional conversion reaction. This represents both a diagnostic and therapeutic dilemma, in extreme cases leading to unnecessary diagnostic tests and their associated complications and costs. Early suspicion and knowledge of functional gait disorders may expedite the correct diagnosis and the institution of appropriate therapy, shortening hospital stay and eliminating unnecessary procedures. This case study reviews two patients with unique gait disturbances-astasia abasia and camptocormia. Astasia abasia is the inability to stand or walk in the absence of other neurologic abnormalities. Camptocormia is characterized by exaggerated trunk flexion of functional etiology. Both patients demonstrated rapid resolution of symptoms after psychiatric intervention. PMID- 2256811 TI - Recovery from vegetative state of six months' duration associated with Sinemet (levodopa/carbidopa). AB - Certain pharmacologic interventions may improve outcome for brain injury in animals and humans. Medications affecting the dopaminergic pathway appear to be important. We present the case of a 24-year-old man with traumatic brain injury who remained unresponsive to commands and unchanged for six months despite periodic aggressive therapy. Within days of beginning Sinemet (levodopa/carbidopa), the patient became conversant and responsive. The reported low likelihood of spontaneous recovery of cognition in patients who are vegetative for six months suggests that Sinemet was responsible for this patient's recovery. In this case, the relatively small risk of side effects from Sinemet was greatly outweighed by the change in functional outcome. PMID- 2256812 TI - Hope and active patient participation in the rehabilitation environment. PMID- 2256814 TI - Measurements of the isometric contractile forces generated by dog periodontal ligament fibroblasts in vitro. AB - One hypothesis for the mechanism of tooth eruption is that the periodontal ligament fibroblasts generate the eruptive force. To assess the force generated, these fibroblasts were obtained by explant culture of ligament from mandibular premolars of a dog and were cultured in collagen gel matrices. The forces generated by them under isometric conditions were continuously measured for 120 h with a strain gauge. At the same time the number of cells in the gel was counted and the force measured was calculated as the force generated by 10(4) cells. Shortly after the start of culture, the force per 10(4) cells increased rapidly; it reached 5.2 X 10(-4) N at 8 h, and then remained at the same level for about 48 h. Our findings suggest that fibroblasts of the periodontal ligament may generate sufficient force for tooth eruption. PMID- 2256813 TI - Immunohistochemical study of the relationship between extracellular matrix and root bifurcation in the mouse molar. AB - In order to investigate epithelial-mesenchymal interaction during root bifurcation, the distribution of type III and I collagen, fibronectin and laminin in the epithelial-mesenchymal junction between the dental epithelia (epithelial diaphragm and interradicular process) and the cells of the dental papilla (or pre odontoblasts) was examined, using maxillary first molar tooth germs of CF1 mice from day 1-16 after birth. Three-dimensional reconstructions of the immunofluorescent patterns were made from serial sections of tooth germs from day 3-9, stained with the antibodies against the collagens. The findings were as follows. (1) Type III collagen was first seen in the epithelial-mesenchymal junction at the tip of the interradicular process, where it sprouted from the epithelial diaphragm, and spread along the interradicular process toward its base, accompanied its extension, and then disappeared on completion of root bifurcation. No staining was seen in the epithelial-mesenchymal junction at the epithelial diaphragm during and after root bifurcation. (2) Type I collagen appeared in the epithelial-mesenchymal junction at the base of the interradicular process, where it sprouted from the epithelial diaphragm and spread toward the tip of the interradicular process, following its extension, and increased on completion of the root bifurcation. No staining was seen in the epithelial mesenchymal junction at the epithelial diaphragm during or after root bifurcation. (3) Fibronectin and laminin remained constant in the epithelial mesenchymal junction, both at the interradicular process and the epithelial diaphragm, during and after root bifurcation. These findings suggest that type III collagen may play a significant role in the early stage of root bifurcation in the molar. PMID- 2256815 TI - The mechanical properties of the dentine and cement of the tusk of the narwhal Monodon monoceros compared with those of other mineralized tissues. AB - Values for Young's modulus of elasticity, ultimate and yield stresses, ultimate and yield strains, work under the stress-strain curve and work of fracture were obtained from tensile and bending tests on specimens of narwhal tusk dentine and cement, femoral bone from young and mature cattle, and reindeer antler. Compared with the cattle bone the narwhal tissues had low Young's moduli, low yield stresses, rather low ultimate stresses and high ultimate strains. In all these properties they were similar to reindeer antler. The calcium content and hardness of the narwhal tissues were compared with those of human and cattle dental tissues. The narwhal dentine was considerably softer and less mineralized than human and cattle dentine. Human cementum was softer and less mineralized than cattle cementum, and was like narwhal cementum. In general, the mechanical properties of the narwhal tusk tissues were as would be expected from their mineral content, except that the stiffness of the cementum was low. It is likely that narwhal dentine is not very similar to human and cattle dentine in its mechanical properties. PMID- 2256816 TI - Motor-evoked potentials in masseter muscle by electrical and magnetic stimulation in intact alert man. AB - The electromyographic responses of the masseter after different types of transcranial stimulation were recorded with surface and needle electrodes. Magnetic stimulation at 4 cm lateral to the vertex on the biauricular line elicited MEPs in the contralateral masseter (latency 6.9 ms) due to activation of motor cortex or adjacent elements along the cortico-nuclear pathway. The ipsilateral responses to the same stimuli and to more lateral ones had shorter latencies and were ascribed to direct stimulation of the trigeminal nerve, probably its intracisternal portion. This was also the probable origin of the ipsilateral MEPs after both anodic and cathodic bipolar electrical stimulation at 7 and 11 cm lateral to the vertex on the biauricular line. PMID- 2256817 TI - An immunocytochemical study of the morphological reaction of nerves containing calcitonin gene-related peptide to microabscess formation and healing in rat molars. AB - Pulpal inflammation was induced by cutting a class V cavity to within 0.1-0.3 mm of the pulp on the mesial aspect of maxillary and mandibular first molars at the cervical line. The exposed dentine was briefly acid-etched and left open to the mouth until the animals were killed. Histological examination of teeth 4 days after injury showed microabscesses, blood vessel dilation and increased numbers of terminal nerve sprouts around the lesion and in radicular pulp and dentine. Specimens at 7, 11, 21 and 35 days after injury showed progressive healing of the lesions with the formation of reparative dentine and a coincident return to a normal patterns of innervation in the remaining pulp. Thus pulpal nerves are not static structures, but rather are capable of rapid change in response to inflammation. The morphological association of CGRP-immunoreactive nerve fibres with the edges of the healing lesions and with zones of reparative dentine suggests a role for these fibres and for the neuropeptide CGRP in the healing response of pulpal tissue. PMID- 2256818 TI - The influence of varying the electrical frequency of sympathetic nerve stimulation on fluid and calcium secretion of the rat parotid salivary gland. AB - The effects of varying this frequency were studied in the absence and presence of the specific adrenergic antagonists. There were no appreciable differences in fluid and calcium secretion at different frequencies of stimulation when the nerve was stimulated alone or in the presence of the selective antagonists. Thus, it is difficult to differentiate between the effects of alpha- and beta adrenergic receptor stimulation by varying the frequency of nerve stimulation. The findings also confirmed that both types of receptors are activated together when the sympathetic nerve is stimulated. beta-Adrenergic receptors play a major role in secretion of both fluid and Ca; alpha-adrenergic receptors seem to have a minor role in their regulation. PMID- 2256819 TI - The expression of colligin/hsp47 after stress in human periodontal fibroblasts in vitro. AB - Fibroblasts from human periodontal ligaments were grown in vitro. The levels of collagen and total protein in these cells were compared with subject- and passage matched gingival fibroblasts. In 3 subjects the levels of both were greater in ligament than in gingival fibroblasts. These increased levels were also associated with increased levels of proteins reacting with anti-colligin/hsp47 antibodies on SDS-PAGE. Ligament and gingival fibroblasts were subjected to heat shock, sodium arsenite and the amino acid analogue AZC. These studies showed that (a) sodium arsenite and AZC enhanced the cellular levels of hsp47 in both types of fibroblast, (b) the colligin/hsp47 levels expressed were associated with elevated levels of protein and collagen production and (c) the presence of colligin/hsp47 was decreased under conditions of serum deprivation. PMID- 2256820 TI - The secretory characteristics of epidermal growth factor in human saliva. AB - A series of unstimulated and stimulated saliva samples from healthy volunteers was tested for EGF by radioimmunoassay. Salivary EGF, like other salivary constituents, was secreted in a diurnal pattern. On stimulation the rate of EGF secretion doubled but the concentration fell by 70% because of dilution by salivary fluid. EGF secretion was positively related to saliva flow (p = 0.00001) but the coefficient of correlation was low (r = 0.47). Over a period of 30 min continual salivary stimulation, EGF was released in a bimodal pattern with peaks occurring at 3 and 12 min. Subsequently, EGF secretion remained stable at a rate of release that was approx. 80% of the initial peak value (7.4 ng/min). Chromatography indicated that both high and low molecular-weight forms of EGF were present in unstimulated and stimulated saliva and that the low-weight form predominated. However, the proportion of high molecular-weight EGF increased from 18 to 38% of the total on short-term (3 min) stimulation. PMID- 2256821 TI - Ablation of submandibular salivary glands in rats provokes a decrease in plasma luteinizing hormone levels correlated with morphological changes in Leydig cells. AB - This work was designed to determine whether changes in plasma and hypophyseal levels of LH are the source of the previously reported atrophy of testicular interstitial tissue following ablation of submandibular salivary glands. The plasma and hypophyseal levels of LH were assayed, and testicular sections examined by electron microscopy in rats, weighing 230-260 g, whose submandibular glands had been removed. Twenty days after sialectomy, the rats were killed, and the pituitary glands removed, homogenized and frozen until used in LH-RIA like the blood samples. Testes were removed and fixed in osmic acid. There was a significant decrease in plasma LH levels in operated animals when compared with sham-operated controls (47.28 +/- 7 ng/ml versus 70.42 +/- 8; p less than 0.02), but the hypophyseal LH content was not significantly modified. Electron microscopy mainly showed important changes in the morphology of the Leydig cells, with a distinct reduction in the number of mitochondria and elements of the smooth endoplasmic reticulum. These findings suggest a physiological involvement of submandibular glands in a possible endocrinological link with the gonadotropic axis. PMID- 2256822 TI - Separation of the proteins of rat parotid saliva by hydrophobic-interaction chromatography. AB - Parasympathetically-evoked rat parotid salivary proteins were resolved into 11 peaks by hydrophobic-interaction chromatography. SDS-PAGE indicated that most peaks contained a single major component and that only one major protein was not chromatographed. The findings indicate that hydrophobic-interaction chromatography can be used in the quantification of changes in individual salivary proteins under different experimental conditions, and in the purification of individual salivary proteins. PMID- 2256823 TI - A histochemical study of the effects of high doses of sodium fluoride on dipeptidyl peptidase II activity in the rat incisor ameloblast. AB - Female Wistar rats, 3 weeks old, were given sodium fluoride in saline solution (isotonic) by intraperitoneal injection at a dose of either 0, 10 or 20 mg per kg body weight. This treatment was given 9 times over 4.5 days. After fixation by perfusion and demineralization in neutral EDTA, hemi-mandibles were sectioned in a cryostat. Sections were stained for dipeptidyl peptidase II activity, using the specific substrate Lys-Ala-MNA and the coupler Fast Blue B for histochemical localization. Staining indicative of dipeptidyl peptidase II was found in the enamel organ of the incisor, particularly in cells of the stratum intermedium and in both secretory and maturation ameloblasts. This staining was markedly reduced in ameloblasts of rats given either 10 or 20 mg sodium fluoride per kg body weight. PMID- 2256824 TI - Creation of a chimaeric periodontium in the rat by isotopic tooth germ transplantation. AB - The purpose of this work was to develop and test a chimaeric periodontium in which it would be possible to distinguish between connective tissue cells of odontogenic and oral mucosal origin. The recombinant periodontium was created by transplanting first maxillary molar tooth germs with their follicles from 1-3-day old hooded Lister rats into the corresponding evacuated crypts of 6-9-day-old histocompatible recipients of the same strain. Of 71 transplants, 22 had formed erupted teeth 3 weeks later, with dentogingival junctions and periodontal ligaments histologically similar to those of control teeth. The recombinant nature of the graft periodontium was confirmed by incubating tooth germs in vitro with tritiated thymidine before grafting them, and then demonstrating radiolabelled nuclei in the dentogingival junctions formed by the transplants. Labelled cells were randomly distributed within the periodontal ligament and predominantly near to the basement membrane of junctional epithelium. PMID- 2256825 TI - Fibrinous reaction occurs until 8 days after intraocular lens implantation. PMID- 2256826 TI - Quantification of afferent pupillary defect by double polarized filter. PMID- 2256827 TI - The cocaine test and Horner's syndrome. PMID- 2256828 TI - Amiodarone-induced lens opacities: an 8-year follow-up study. PMID- 2256829 TI - Sunlight and age-related macular degeneration. PMID- 2256830 TI - Physicians, lenses, and myopia. PMID- 2256831 TI - Microbial keratitis with crack cocaine. PMID- 2256832 TI - A retinal pigment epithelium tear in a patient with angioid streaks. PMID- 2256833 TI - Papilledema in a patient with aplastic anemia. PMID- 2256834 TI - Ocular penetration of thiabendazole. PMID- 2256835 TI - The clinical appropriateness initiative--cataract management study. PMID- 2256836 TI - Does anyone know how to differentiate a 'functional' defect from a cosmetic one? PMID- 2256837 TI - The pretear characteristics of pigment epithelial detachments. A study of 40 eyes. AB - Retinal pigment epithelial tears are a major complication of pigment epithelial detachment (PED) in the elderly. We observed the pretear process of PED in 38 patients (40 eyes) to identify characteristic angiographic changes. Before the tear occurred, the filling pattern of the PED underwent alterations, including an increase in the size and a modification in the shape of the PED (27 eyes); the development of notches (14 eyes); and the onset or increase of subretinal fluid, hard exudates, and/or hemorrhages (30 eyes). The most noteworthy feature was the uneven filling of the PED, with a remarkably hypofluorescent central area that remained dark until the late angiographic frames (24 eyes). Conversely, hyperfluorescence appeared early at the margins of the PED, increased progressively, and sometimes demonstrated a crenated edge. The high risk of tearing indicates that laser treatment of the retina should be considered carefully in the presence of these angiographic features. PMID- 2256838 TI - Retinal pigment epithelial tears through the fovea with preservation of good visual acuity. AB - We describe two patients with spontaneous retinal pigment epithelial tears through the fovea who have maintained at least 20/40 visual acuity for 1 year and 3 years following the rip. Both patients had long-standing serous detachments of the retinal pigment epithelium associated with age-related macular degeneration prior to the development of the tear. Each tear was at least five disc areas in size and centered on the fovea. Foveal fixation was documented despite the presumed absence of pigment epithelium. This observation suggests either that there may be remaining or redundant pigment epithelium or that pigment epithelium directly beneath the central macula is not required for maintenance of 20/40 visual acuity. PMID- 2256839 TI - Threshold perimetry in tilted disc syndrome. AB - Twelve consecutive patients (17 eyes) with tilted disc syndrome underwent quantified visual field examination with the G1 Octopus program (Interzeag AG, Schlieren, Switzerland). Visual fields were abnormal in all cases. Although field loss was more pronounced in the superotemporal quadrant (P less than .001), it also involved the other three quadrants, thus demonstrating that optic nerve hypoplasia in tilted disc syndrome is apparently not entirely sectorial. Linear regression analysis showed that an increase in mean defect correlated with increase in myopic refractive error (P less than .05). However, the increase in myopic refractive error was found to be related to a decrease in corrected loss variance (P less than .05), indicating that in tilted discs with higher myopia, field loss is more homogeneous. With this series of patients, short-term fluctuation was within normal ranges in all visual fields, showing that this may be an additional clue for differential diagnosis from acquired disorders. PMID- 2256840 TI - Removal of radiation-induced cataracts in patients treated for retinoblastoma. AB - Experience with removal of radiation-induced cataract in patients treated for retinoblastoma is limited. We retrospectively reviewed the records of 38 patients with retinoblastoma (42 eyes) who underwent removal of radiation-induced cataract from 1973 to 1989. Nineteen eyes (45%) without macular tumors or severe radiation complications had final visual acuities in the range of 20/20 to 20/50. One eye (2.4%) developed a rhegmatogenous retinal detachment and four eyes (9.5%) were noted to have amblyopia after cataract removal. Three eyes (7%) developed retinoblastoma recurrence, one with extension of retinoblastoma into the subconjunctival space through the previous sclerotomy. Exenteration was performed and the patient was alive after 8 years. Cataract removal can be visually beneficial in selected patients with radiation-induced cataracts. PMID- 2256841 TI - Tonometer utilization, accuracy, and calibration under field conditions. AB - A field survey conducted in 94 ophthalmologists' offices in our immediate area assessed the accuracy of tonometers in daily use. One hundred eighty-five instruments were examined: 127 were slit lamp mounted, 48 were hand held, and 10 were noncontact devices. Nineteen percent of applanation tonometers were outside the manufacturers' specifications (1 mm Hg of the calibration) and 4.5% were more than 2 mm Hg in error. The error was constant across the scale. Hand-held applanators were less accurate than those on slit lamps (P less than .02); the latter demonstrated an association between accuracy and age (P less than .05) and heavier use (P less than .01). Annual recalibration was performed in 86% of instruments. Those practitioners who themselves performed the calibration had the most accurate instruments. Less than 15% knew how to perform the calibration check. PMID- 2256842 TI - Color matching and foveal densitometry in patients and carriers of an X-linked progressive cone dystrophy. AB - We describe a family with an as yet undescribed form of X-linked progressive cone dystrophy in a five-generation pedigree, from which we report here the results of 17 male patients and 31 obligate and 13 possible female carriers. The affected males showed the characteristic picture of cone dystrophy. Foveal cone photopigment density was impaired (judged from anomaloscope settings and foveal densitometry), even at an early stage of the disease. The carriers showed no fundus abnormalities, except occasional changes due to myopia. The anomaloscope demonstrated mild pseudoprotanomaly in 27 of 31 obligate carriers and in six of 13 possible carriers. Foveal densitometry findings performed in 11 carriers always agreed with the anomaloscope findings. We conclude that the findings of pseudoprotanomaly and abnormal density differences in females of this family were the only ocular abnormalities and thus are indicative of the carrier state. PMID- 2256843 TI - Familial trigeminal anesthesia. AB - Familial congenital trigeminal anesthesia as an isolated abnormality is an unusual disorder. To our knowledge, only one family has previously been reported. We report here a family with three affected members demonstrating facial anesthesia, bilateral corneal changes, and nasal septal damage secondary to self traumatization. Magnetic resonance imaging demonstrated hypoplasia of gasserian ganglia and trigeminal nerves in the affected father of two affected sons. The pathogenesis of this disorder appears to be congenital hypoplasia of the trigeminal nerves and gasserian ganglia that is inherited in a dominant fashion. PMID- 2256844 TI - Pars plana vitrectomy for acute retinal detachment in penetrating ocular injuries. AB - We studied 41 eyes with acute retinal detachment after penetrating ocular trauma in a retrospective cohort analysis. Pars plana vitrectomy was performed in 28 eyes, while the remaining 13 eyes had only primary repair and closure of the wound. The two groups differed in the type of trauma (more gunshot wounds in the vitrectomy group and more blunt injuries in the nonvitrectomized group). Visual success (visual acuity of 5/200 or better) was observed in 10 (37%) of the eyes treated by vitrectomy compared with one (8%) of the eyes in the nonvitrectomy group. Anatomic success was achieved in 21 (75%) of the eyes in the vitrectomy group but in only one (8%) of those in the nonvitrectomy group. Enucleation or phthisis was observed in seven (54%) of the eyes in the nonvitrectomy group compared with only five (18%) in the vitrectomy group. Significant prognostic factors for anatomic outcome in the vitrectomy group were the location of the laceration and the presence of the lens. PMID- 2256845 TI - Vitreous fluorophotometry in insulin-dependent diabetes mellitus. Correlation with microalbuminuria and diastolic blood pressure. AB - Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure. PMID- 2256846 TI - Respiratory epithelium in a cystic choristoma of the limbus. AB - A female newborn had a cystic, whitish gray mass at the inferotemporal limbus of the left eye. At age 3 weeks, the newborn underwent excision of the tumor, corneal patch grafting, and superior sector optical iridectomy. Histopathologic and electron microscopic examination of the excised tissue revealed a choristoma consisting of cysts lined with respiratory epithelium. To our knowledge, respiratory epithelium in a limbal choristoma has not been previously reported. PMID- 2256847 TI - Retinal toxicity of intravitreal gentamicin. AB - The short- and long-term effects of a 10-mg dose of intravitreal gentamicin were studied in the subhuman primate eye with regard to the changes in clinical appearance, fluorescein angiography, electroretinography, histopathologic finding, and electron microscopy. The gentamicin produced retinal whitening with a cherry-red spot, generalized vascular incompetence, diffuse retinal necrosis, thrombosis of the large retinal blood vessels, widespread loss of the retinal capillary pericytes and endothelial cells, and a rapid extinction of the electroretinogram. PMID- 2256848 TI - Laser sclerostomy by pulsed-dye laser and goniolens. AB - We describe an ab-interno laser sclerostomy procedure using the method termed dye enhanced ablation with a slit-lamp delivery system and special goniolens such that only the laser light beam penetrates the anterior chamber. The procedure uses a microsecond-pulsed-dye laser emitting at 666 nm and iontophoresis of methylene blue dye (absorption of 668 nm) into the sclera at the limbus to enhance the absorption of the laser light. We compared the number of pulses needed to perforate excised human sclera at pulse durations of 1.5, 20, and 300 microseconds. Pulse durations of 1.5 and 20 microseconds required 20 pulses or fewer to perforate excised human sclera with pulse energies of 75 to 100 mJ. The ab-interno laser sclerostomy procedure was performed in 54 eyes of Dutch-belted rabbits with pulse durations of 1.5 or 20 microseconds and a 100- or 200-microns incident spot diameter delivered using a CGF goniolens. Full-thickness fistulas were successfully created at both pulse durations in approximately 80% of eyes treated. A range of three to 25 pulses was required to perforate sclera with slightly fewer pulses and lower pulse energies at 1.5 microseconds compared with 20 microseconds. There were no significant complications from the procedure. This technique could permit filtration surgery to be performed on an outpatient basis. PMID- 2256849 TI - Acute retinal pigment epithelial tear. PMID- 2256850 TI - Lamellar ichthyosis and congenital ectropion. PMID- 2256851 TI - Anterior ethmoid anatomy facilitates dacryocystorhinostomy. AB - The ethmoid air cell labyrinth lies adjacent to the medial orbital wall, extending even beyond the sutures of the ethmoid bone. Its anatomic relationship to the lacrimal sac fossa is important in lacrimal surgery. We evaluated computed tomographic scans of 190 orbits with normal ethmoid anatomy to define the anatomic relationship of anterior ethmoid air cells to the lacrimal sac fossa. In 93% of the orbits, the cells extended anterior to the posterior lacrimal crest, with 40% entering the frontal process of the maxilla. This anatomic relationship may be used to facilitate the osteotomy during dacryocystorhinostomy. During a 10 year period (310 cases), one of us routinely entered the anterior ethmoid air cells to initiate the osteotomy during dacryocystorhinostomy. This technique has helped to avoid lacerations of the nasal mucosa. PMID- 2256852 TI - A new ophthalmic electronic videoendoscope system for intraocular surgery. AB - A new ophthalmic electronic videoendoscope system has a 20-guage probe for intraocular observation, a standard size for vitreous microsurgical instruments, and both endoscopic and operating microscopic images are displayed on a split screen monitor system to provide surgeos a simultaneous view of both images. Using this endoscope system at any time during surgery, surgeons can examine the intraocular structure such as the ciliary sulcus, pars plana, or vitreous base and obtain valuable but otherwise unobtainable information for completing the surgery. PMID- 2256853 TI - Undergraduate education in obstetrics and gynaecology in Australia and New Zealand, 1989. AB - Medical schools in Australia and New Zealand provide an average of 10.7 weeks for instruction in obstetrics abd gynaecology. The stated aims and objectives in 14 clinical schools vary from none at all to those which establish the programme with great clarity. The learning exercises provided vary from the conventional, ward and clinic-based to those with an accent on observing closely a mother, her baby and her family. Newer methods for learning about pelvic examination have not been widely adopted. Schools expect students to gain experience in an average of 9 vaginal deliveries. Competition with midwives for available deliveries was described by 9 clinical schools. The survey shows a need for greater emphasis in text books on communication skills and psychological aspects of patient care. PMID- 2256854 TI - Acute and subacute polyhydramnios in singleton pregnancies. AB - Over a 10-year period when 51,022 singleton infants were delivered, 19 pregnancies (1 in 2,685) were complicated by acute polyhydramnios 17 (1 in 3,000) by subacute polyhydramnios and 501 (1 in 102) by chronic polyhydramnios. The incidence of major congenital malformations in singleton pregnancies associated with acute polyhydramnios was 63% and the perinatal mortality rate was 74%. When subacute polyhydramnios occurred in singleton pregnancies, the incidence of major congenital malformations was 65%, similar to acute polyhydramnios, but the perinatal mortality rate was only 35%. The comparable figures for chronic polyhydramnios in singleton pregnancies were a major malformation incidence of 14% and perinatal mortality rate of 10%. The type of onset of polyhydramnios, acute, subacute or chronic is therefore the most important indicator of prognosis. In patients with gross polyhydramnios, acute renal failure must be specifically excluded. PMID- 2256855 TI - Acute polyhydramnios in twin pregnancies. AB - This paper reports the experience with acute polyhydramnios complicating twin pregnancies at the Mercy Maternity Hospital for the 10-year and 2-month period from January, 1979 to February, 1989 during which time there were 13 such cases, an incidence of 1 in 4,044 pregnancies. Acute polyhydramnios complicated 1.7% of all twin pregnancies. The perinatal mortality rate was 88.5% and accounted for 16.7% of the perinatal deaths in twins. No major fetal malformations were found. One case of acute polyhydramnios was successfully managed with ultrasonographically guided serial amniocenteses. The management of this rare condition is considered. PMID- 2256856 TI - The significance of polyhydramnios diagnosed during labour or at caesarean section. AB - In the 38 cases of polyhydramnios reported here the diagnosis was made only at the time of artificial rupture of the membranes to induce or augment labour, or at Caesarean section. Usually this was a benign finding often associated with overweight in the mother (60%) or baby (39.4%). However there was an increased incidence of major congenital abnormality (13.1%) resulting in a high perinatal mortality rate (10.5%); the paediatrician should therefore be alerted prior to delivery of these patients. PMID- 2256857 TI - Caudal analgesia by the obstetrician. AB - The results of 670 consecutive caudal blocks performed by the author for operative obstetrics over 20 years is reported. There was no morbidity attributable to the technique. Satisfactory analgesia was not achieved in 83 patients and obesity was not a major cause of failure. The causes of these failures are discussed. It is recommended that caudal analgesia continues to be used for operative vaginal obstetrics. PMID- 2256858 TI - Cytogenetic studies in perinatal death. AB - Following tissue culture cytogenetic studies were performed on tissue obtained from 136 fetuses who died in the perinatal period (98 stillbirths and 38 neonatal deaths). The gestational age of the stillbirths was evenly distributed between 20 and 40 weeks (1 was 42 weeks) while 74% of the neonatal deaths were term babies. Analyzable metaphases were obtained in 45 stillbirth specimens (46%) and 32 neonatal specimens (84%). Abnormal karyotypes were identified in 7 of the stillbirths (15.5%) and 8 of the neonatal deaths (25%) and all these were from babies with congenital anomalies identified at autopsy. Time delays were crucial to the success of culture from stillbirths, but specimens obtained from neonatal deaths could be grown successfully up to 3 days after death. Generally the placenta was more viable than other tissues, including skin, cartilage and muscle. Whereas growth was obtained in 69% of fresh unexplained stillbirths, no tissue from the macerated stillbirths grew. This is a group which may have a high abnormality rate. We recommend that if fetal assessment during pregnancy suggests a compromised fetus and there are no maternal factors to account for this, an amniocentesis be performed. PMID- 2256859 TI - Perinatal mortality rates: Holland versus the Hunter Valley. AB - A public comment to the effect that Holland has a superior perinatal mortality rate to that in Australia prompted an analysis of this proposition. In the region of Newcastle and The Hunter Valley of New South Wales, detailed information on perinatal mortality over a 5-year period (1983-1987) was available. The data suggest that the perinatal mortality rate in this region is, in fact, superior to that in Holland. The definition of perinatal mortality differs greatly between the 2 countries; and this fact, perhaps unappreciated, might lead to the superficial perception that Holland's perinatal mortality rate is superior to our own. PMID- 2256860 TI - An investigation of the maternal antecedents of perinatal mortality in 2 large teaching hospitals. AB - Perinatal mortality reviews are a form of quality assurance, and the classification of perinatal mortality would be most useful if it assisted in strategies for prevention. Whilst the value of clinicopathological (autopsy) and separate neonatal classifications is recognized, the Whitfield classification, modified for Australian conditions and applied to 393 cases, clearly identified the major obstetric problems leading to perinatal death, and may therefore contribute to continuing improvement in prenatal care. PMID- 2256861 TI - Birth-weight of newborns to Chinese women subsequent to a previous abortion. AB - The mean birth-weight of firstborns of women was significantly higher when there was a previous abortion. The increase was 73.5 and 119.4 g in newborns of women with an induced and a spontaneous abortion respectively. This trend of significant increased birth-weight among firstborns of women with either a previous induced or spontaneous abortion continued for male infants, in recent migrants, and in subjects aged 20-24 and 30-34 years. Stepwise logistic regression analyses showed that a history of an induced or a spontaneous abortion increased the birth-weight of the firstborns, while short maternal stature and female newborn were associated with decreased birth-weight. For low birth-weight, a previous abortion was not selected into the regression models but short maternal stature and female newborns continue to contribute to low birth-weight. Prematurity and mean gestation were found not to be associated with previous abortion using logistic regression analyses. PMID- 2256862 TI - Hysteroscopic adhesiolysis. PMID- 2256863 TI - The effect of condom use on cervical intraepithelial neoplasia grade I (CIN I). AB - A prospective, controlled study of condom use in patients with histologically proven CIN I was undertaken. Forty-six patients were studied, 22 by random allocation and 24 by nonrandom allocation to either condom use or non-condom use for 6 months. At the end of this time, patients were reassessed cytologically, colposcopically and histologically. There was no significant difference between the groups with respect to outcome. Six patients' lesions (13%) progressed in this period, 5 (11%) to CIN III. Condom usage is not an effective treatment for CIN I. PMID- 2256864 TI - Is genital human papillomavirus infection always sexually transmitted? AB - The occurrence of genital human papillomavirus (HPV) infection was studied prospectively by colposcopy and histology in 43 virginal and 162 sexually active women attending a colposcopy clinic. The study also included 111 husbands of the latter group. By colposcopic criteria, the prevalence of HPV infection was 51.1% in the virginal and 69.1% in the sexually active women. The prevalence was 77.1% among men whose wives had HPV infection compared to 13.3% among men whose wives did not have the infection (p less than 0.01). There was a strong association in genital HPV infection between husbands and wives as expected from a sexually transmissible disease. However, the high prevalence of the infection among the virginal women indicated that transmission of HPV by nonsexual modes was common. Genital HPV infection is ubiquitous and in women is not exclusively a venereal disease. PMID- 2256865 TI - Cancer of the uterine cervix and screening of Aboriginal women. AB - Carcinoma of the cervix has not been widely reported as an important health problem for Aboriginal women. From four sources, we have studied cervical cancer death rates, abnormalities detected by cervical cytology screening, and the proportion of women who had been screened. First, from the Northern Territory for the years 1979-1983, we present a relative risk of 6.3 (95% confidence interval, 3.0-11.6) for cervical cancer deaths in Aboriginal women compared with all Australian women. Second, the screening and disease rates in Aboriginal women were profiled within a large laboratory in Victoria. Since 1984, a fourfold increase in the number of smears taken at Aboriginal health services is apparent. In women attending these services, a high rate of significantly abnormal smears is evident. Third, to study the extent of screening, we interviewed Aboriginal women in a Victorian country setting and fourth, we examined a random sample of medical records from an Aboriginal Health Service. The proportion screened at least once rose from 5/47 (11%) among women whose most recent consultation with the Health Service was during the years 1974-1980 to 51/170 (31%) women who attended from 1981-1987 (p less than 0.01). Aboriginal communities may interpret these trends favourably as they encourage their women to be screened regularly to reduce cervical cancer mortality. PMID- 2256866 TI - Long-term radiographic follow-up of the sella turcica in hyperprolactinaemic women. AB - Seventy-three hyperprolactinaemic women were followed up with radiographic examinations (lateral and posteroanterior coned down views) of the sella turcica for 5 to 13 years during which time all but one had received treatment with bromocriptine. Progression of the sellar asymmetry occurred in 25 women (7 during pregnancy), 14 had regression of their changes in the pituitary fossa while 34 did not show any changes in the configuration of the sella turcica. Prolactin levels in serum, duration of bromocriptine therapy or sellar configuration could not predict later radiographic progressive or regressive changes of the sella turcica. The clinical course was benign in the majority of the women with signs of prolactin-producing adenomas. The risk of serious tumour enlargement seems to be very small. We were not able to demonstrate any parameter which could predict the growth or shrinkage of the tumour. Routinely repeated radiographic sellar examinations are unnecessary in the vast majority of hyperprolactinaemic women. PMID- 2256867 TI - A case of multiple (5) ectopic pregnancies, ultimately resulting in a twin pregnancy after in vitro fertilization and embryo transfer. AB - The history of a woman with anovulation, tubal disease and 5 ectopic pregnancies is presented. She finally succeeded in having a family by conceiving twins in her eighth attempt at in vitro fertilization. PMID- 2256868 TI - Permanent voice change resulting from Danazol therapy. PMID- 2256869 TI - Evidence against diathermy as a beneficial treatment for human papilloma virus infection of the cervix. PMID- 2256870 TI - Serum CA-125 levels in women with endometriosis. PMID- 2256871 TI - Effects of hypergravity on lung carcinoma cells maintained in continuous organotypic culture. AB - The effects of hypergravity levels ranging from 1 to 15 g were studied on A549 lung adenocarcinoma cell line, cultivated as nodules. This organotypic culture model preserves as closely as possible the cellular structures and differentiation functions of the in vivo situation. Nodules submitted to hypergravity conditions for 27 d did not show any change of cell growth, protein and DNA contents, compared with controls. Also, cellular differentiation, as regards intracellular phospholipid composition and more particularly phosphatidylcholine content, appeared undisturbed. The only obvious effect of hypergravity was a modification of the structural organization, with a disappearance of the large alveoli present at the surrounding of control nodules and the development of a dense cellular mass instead. PMID- 2256872 TI - Impairment of rat polymorphonuclear neutrophilic granulocyte phagocytosis following repeated hypobaric hypoxia. AB - Exposure of rats to repeated hypobaric hypoxia (17 h at 0.5 atm for 0-7 d) induced significant reduction of the phagocytic capacity of peripheral blood polymorphonuclear neutrophilic granulocytes (PMNL). In addition, the hypoxia induced a significant increase of the hematocrit, hemoglobin, thrombocyte, and total leukocyte concentrations. Differential counting of peripheral blood revealed significant granulocytosis. An increase of the concentration of corticosterone was demonstrated following 2 d of hypobaric hypoxia, whereas 5 d later the corticosterone concentrations were similar to that of the controls. The reduced PMNL phagocytic capacity observed following repeated hypobaric hypoxia may have consequences for host defence in situations of hypoxia exposure. PMID- 2256873 TI - Adverse effects of dietary and furosemide-induced sodium depletion on thermoregulation. AB - In this study, the diuretic furosemide was used in combination with dietary sodium (Na) restriction to quantify the effects of moderate to severe Na depletion on heat tolerance in a validated model of heat stress in rats. Rats were subjected to an Na depletion regimen as follows: a control group (I, n = 17) had free access to a normal diet and tap water; group II (n = 20) consumed the same normal diet and tap water, but was treated with the diuretic furosemide at a dose of 10 mg.kg-1.d-1, ip; group III (n = 18) had free access to an Na-free diet and deionized drinking water; group IV (n = 21) consumed the same Na-free diet and electrolyte-free water, but was also treated with furosemide. Both the dietary and drug manipulations affected significant (p less than 0.05) negative electrolyte and water balances. Group IV consistently exhibited the greatest decrements. Following the 4-d depletion all four groups were acutely exposed to a 42 degrees C, 25-30% rh environmental heat stress during which time core body temperature increased. The time required for rectal temperature to reach 42.6 degrees C was significantly (p less than 0.05) decreased from a time of 242 +/- 8 min in the control group to 176 +/- 14, 181 +/- 8, and 111 +/- 11 min in groups II, III and IV, respectively. We concluded that Na deprivation and diuretic treatment can elicit a 25-50% reduction in heat tolerance due to electrolyte depletion and dehydration. These data confirm that during environmental heat stress uncompensated negative Na balance may predispose an individual to heat illnesses. PMID- 2256874 TI - Catecholaminergic responses to rotational stress in rat brain stem: implications for amphetamine therapy of motion sickness. AB - The fact that amphetamine, a noradrenaline releaser, prevents motion sickness leads the hypothesis of Wood and Graybiel that the noradrenergic neuron system in the brain stem acts against the development of motion sickness. To evaluate the hypothesis, the effects of rotational stress on the turnovers of noradrenaline and dopamine in the rat brain stem were examined. Rats were rotated about two axes simultaneously (double rotational) or about one axis (single rotation) for 60 min. Measurement of kaolin intake (pica) induced by rotation, as an index of motion sickness, showed that double rotation produced motion sickness, whereas single rotation did not. Both single and double rotation significantly increased the turnovers of noradrenaline and dopamine in the brain stem. However, there were no significant differences between the increases in catecholamine turnover induced by double and single rotations. Moreover, pretreatment of rats with methamphetamine (5 mg/kg) just before double rotation, which prevented the induction of motion sickness by double rotation, did not affect increases of the catecholamine turnover in the brain stem by double rotation. These findings do not support the hypothesis of Wood and Graybiel, suggesting that the catecholaminergic neuron systems in the brain stem are not involved in motion sickness and that the therapeutic effect of methamphetamine is not due to its direct effect on the brain stem. PMID- 2256876 TI - A case of decompression sickness at 2,437 meters (8,000 feet). AB - Among aviators, decompression sickness is a condition that occurs almost exclusively at altitudes above 6,098 m (20,000 ft). Several reports have been published describing the development of decompression sickness after altitude exposures of 3,049 to 4,878 m (10,000-16,000 ft). In most of these cases, the affected individual had a previous history of pain in the involved area due to prior trauma or surgery, or had other risk factors for decompression sickness, such as obesity. Few of these reports have confirmed the presence of decompression sickness by a test of pressure. A case is reported here of multiple joint pains developing after a rapid decompression at 2,439 m (8,000 ft), which improved during descent and rapidly resolved with recompression therapy. There was no prior history of joint pain, trauma, or diving. A brief discussion of decompression sickness is included. PMID- 2256875 TI - Use of phenytoin in the prevention of motion sickness. AB - In a placebo-controlled double-blind crossover pilot study of acute Coriolis induced motion sickness treatment/prevention in humans employing an anticonvulsant dose of phenytoin, a mean increase in tolerance to motion stress from 4.87 min (S.D. = 5.55) to 46.87 min (S.D. = 32.6) was obtained. This represents a greater than fourfold improvement in efficacy over any currently available single agent and is more than twice as effective as the scopolamine/dexadrine combination. There were none of the usual side effects of blurred vision, dizziness, dry mouth, or sedation. PMID- 2256877 TI - The risk of developing decompression sickness during air travel following altitude chamber flight. AB - Approximately 35,000 students are trained annually in United States Air Force (USAF) altitude chambers. Students who depart the training site via aircraft on the same day as their altitude chamber exposure may place themselves at increased risk for decompression sickness (DCS). Air travel as a passenger in the immediate post-chamber flight period is unrestricted by current USAF regulations. A retrospective study was conducted to assess the potential risk involved in such post-chamber flight travel. During the years 1982-87, there were 292 cases of DCS involving altitude chamber students which were subsequently treated with hyperbaric oxygen therapy. Only seven cases were found wherein the student was asymptomatic prior to air travel and subsequently developed DCS. Because the percentage of students who postpone travel is unknown, a precise relative risk could not be determined. Although the number of cases where sequential chamber and aircraft hypobaric exposures has initiated DCS is small, the potential for such occurrences remains a health concern. PMID- 2256878 TI - Exposure to solar ultraviolet radiation in flight. AB - The ultraviolet radiation (UVR) exposure of airline pilots during flight was measured with ultraviolet-sensitive film badges. The badges were worn by flight crew on the epaulette nearest to the window of either a Boeing 737 or 767 during 18 different flights in 1989. The results showed in every case that the UVR exposure was negligible; a flight lasting several hours resulted in an exposure equivalent to no more than a minute or two outdoors. There is anecdotal evidence that pilots may be at increased risk of developing skin cancer compared with many other occupational groups. The suggestion that this is due to significant exposure to UVR, the main aetiological factor in skin cancer, on the flight deck cannot be sustained. PMID- 2256879 TI - The aeromedical implications of atrial fibrillation. AB - A retrospective study was undertaken to determine the incidence of spontaneous atrial fibrillation (AF) in a group of asymptomatic pilots. The electrocardiograms of 13,037 aircrew members accumulated between 1964 and 1986 were reviewed and those coded for AF were extracted. In each case an attempt was made to investigate factors relating to the onset, course, and prognosis of the AF. Eight subjects (mean age 50.1 years) were found to have AF. Of this group, two had a single isolated episode of AF for which a specific precipitating factor was implicated, three had recurrent paroxysmal AF of which one progressed to chronic persistent AF, and three had chronic persistent AF from the outset. The mean follow-up period for the eight subjects was 13.6 years. The two pilots who had isolated attacks of AF have thus far had no subsequent episodes of AF. Five of the remaining six have been completely well, while one required treatment for an embolus to his left leg. Concerning the aeromedical implications, we believe that pilots demonstrating single isolated episodes of AF in the presence of a normal heart, and in whom recovery is complete, should be allowed to return to full aviation duties on a waiver clause. Patients with chronic AF, lone AF, or paroxysmal AF should be excluded from all flying duties. PMID- 2256880 TI - Retrospective cohort study of duodenal ulcer disease in U.S. Air Force pilots. AB - Current waiver policy for duodenal ulcer (DU) disease in pilots is based on data from civilian populations since little information is available on the course and prognosis of this disease in pilots. The United States Air Force (USAF) waiver file and the Office of Medical Support database were used to identify 100 pilots with onset of DU between 1981 and 1987. A written questionnaire was returned by 86 (86%) of these pilots. The incidence of DU in USAF active-duty pilots was estimated to be 5.0 per 10,000 pilot-years. DU was significantly associated with cigarette smoking. Bleeding ulcers were significantly associated with aspirin use. After 587 person-years of follow-up there were no fatalities; serious sequelae were reported in only 6 pilots, and moderate sequelae in only 12 others. The risk of recurrence of DU in this population was not appreciably higher among those initially presenting with hemorrhage. PMID- 2256881 TI - The electrocardiographic response of females to centrifuge +Gz stress. AB - Women continue to expand their participation in all areas of aviation, including flying high performance fighter aircraft. Acceleration (+Gz) stress is unique to fighter aviation, therefore it is important to thoroughly understand the electrocardiographic (ECG) response to +Gz stress since it reflects a portion of the cardiovascular +Gz tolerance. A comparison of the ECG response to centrifuge +Gz stress between 685 men and 94 women was made from data existing within a centrifuge data repository. The frequency of occurrence of specific types of atrial, ventricular, and the other most frequently observed ECG changes to +Gz stress were compared for females and males. Females had less atrial ectopy; essentially equivalent premature ventricular contractions (PVC's), multiformed PVC's, paired PVC's; less frequent ventricular and supraventricular tachycardia; and more frequent PVC's in a bigeminal pattern and QRS on T PVC's. Sinus arrhythmia, sinus bradycardia, and increased T-waves post +Gz stress were more frequent in males, with ectopic atrial rhythm and atrioventricular dissociation essentially equivalent in males and females. Although few women have participated in either simulated aerial combat maneuver type centrifuge profiles or centrifuge high-G training, they have shown similar ECG changes including conduction and rhythm disturbances infrequently seen in males, such as +Gz-induced right bundle branch block and high-G bradycardia. Based on the currently available ECG response data, women have no demonstrated unique susceptibility to +Gz-induced ECG changes. Therefore, no contraindication exists to initiating additional acceleration research to fully evaluate women's tolerance to the more stressful, higher levels of +Gz stress. PMID- 2256882 TI - The 24th Harry G. Armstrong lecture: U.S. space research programs: future prospects. PMID- 2256883 TI - Major General Harry G. Armstrong: memories of a friendship. AB - Major General Harry G. Armstrong was a well known personality in aviation medicine. Most people, especially the younger generation, recall only his public image as a scientist wholly involved in his research and as a man of great authority. Dr. Evrard recounts some of his memories of this great man in an effort to bring the true personality of Major General Harry G. Armstrong to light. PMID- 2256884 TI - Now there is "20th century disease". PMID- 2256886 TI - Stress inoculation training for smoke divers and free fall lifeboat passengers. AB - The effects of 1 h stress inoculation training on subjective experience, performance, and physiological activation were studied in two fear-provoking situations. In the free fall lifeboat situation, the experimental group reported higher acceptance of the free fall lifeboat concept after the training course than the control group. In the smoke diving situation, the experimental group reported less need of success and reported learning self confidence instead of skills more often than the control group and received less help from the instructor during diving. However, the experimental group reported higher anxiety than the control group during training. There were no differences between groups in saliva cortisol values in either of the two experiments. Effects of stress inoculation training are explained in terms of expectancy theory. PMID- 2256885 TI - Corporate instability is related to airline pilots' stress symptoms. AB - The Symptoms of Stress questionnaire was administered to three random samples of commercial airline pilots. Respondents included 1 group of 212 pilots who were employed by an airline company with a history of corporate instability; and 2 groups, totalling 220 pilots, who were employed by 2 airline carriers with histories of corporate stability. The pilot group employed by the airline with a history of corporate instability reported significantly more stress and depression symptoms and a greater accumulation of symptoms than did the pilot groups employed by the stable airlines. With the advent of airline deregulation and its concomitant changes in the airline industry, including corporate instability, we conclude that the relationship between corporate instability within the aviation environment and the subjective distress reported by pilots suggests the need for further investigation into implications for health and safety. PMID- 2256887 TI - Effect of whole-body vibration on acoustic measures of speech. AB - If Automatic Speech Recognition technology is to be applied in the cockpit, it must deal with speech produced under environmental conditions that may alter the acoustic characteristics of the speech to be recognized. The present study examines the acoustic-phonetic detail of selected words produced under vibration, with the talker wearing an oxygen mask. The duration of words and syllables showed small effects that were inconsistent and statistically non-significant. Statistically significant increases were found in fundamental frequency and in the proportion of energy in the higher frequencies (decreased spectral tilt). The vibration conditions examined had no consistent effect on the center frequencies of the vowel formants measured. PMID- 2256888 TI - EMG analysis of human postural responses during parabolic flight microgravity episodes. AB - Anticipatory postural activity in the trunk and legs precedes rapid shoulder flexion in unit gravity. We tested the hypothesis that anticipatory activity is a component of a single neural command for arm movement by monitoring the surface electromyographic activity of the biceps femoris, paraspinals and deltoid muscles of three subjects during the microgravity phase of parabolic flight. If part of a single command, anticipatory postural activity would be expected to remain intact despite the absence of the body's center of gravity in a reduced gravity environment. However, in at least 75% of the microgravity trials anticipatory biceps femoris activity was absent, indicating a separation of postural and agonist muscle activity. Such a finding suggests that anticipatory postural biceps femoris activity may be initiated independently of agonist (deltoid) activity. PMID- 2256889 TI - Mixed-model segregation analysis of schizophrenia in the Lindelius Swedish pedigrees. AB - To test if familial transmission of schizophrenia is consistent with a model of monogenic inheritance with a multifactorial background, a mixed-model segregation analysis was applied to Swedish pedigrees consisting of 270 probands in 263 nuclear families. Results of the best-fitting mixed-model solutions are consistent with multifactorial transmission and no major gene. However, numerical instabilities prevented formal hypothesis testing, so an irrefutable genetic mechanism remains unidentified. Alternative research strategies that exploit recent advances in molecular genetics are discussed. PMID- 2256890 TI - Response to selection for sensitivity to ethanol hypothermia: genetic analyses. AB - Selective breeding has been used to produce lines of mice differing in sensitivity to the hypothermic effects of ethanol (EtOH). Two genetically independent HOT (insensitive) and two COLD (sensitive) lines are maintained along with two nonselected control (CON) lines. The breeding program is currently in selected generation 14, and HOT and COLD mice differ by about 4 degrees C in selected hypothermic response. Estimates of heritability indicate that approximately 20% of the variance in EtOH-induced hypothermic response in mice is of additive genetic origin. Inbreeding has increased at a rate of about 1.7% per generation and no fertility problems have been detected as a result of selection. Projects designed to evaluate apparent correlated responses to selection are discussed. PMID- 2256891 TI - Influence of coat color genes on seizure behavior in Mongolian gerbils. AB - Seizure tendencies of three separate lines of Mongolian gerbils Meriones unguiculatus carrying three different coat color alleles were investigated. These alleles were agouti (A/-), black or nonagouti (a/a), or sandy (pink-eyed dilution p/p). Each animal was stroked on the back and then placed in a novel cage for 5 min while its seizure activity was measured in terms of latency, duration, and severity (grade). The results indicate that gerbils which are homozygous recessive at the pink-eyed dilution locus (sandy) exhibit less severe and shorter seizures than others. However, gerbils which are homozygous recessive at the agouti gene locus (black) show a shorter latency to manifest seizures than the other animals. These results indicate that the genetic mechanism determining coat color in Mongolian gerbils may also influence the susceptibility of these animals to seizure arising from novel stimulation. PMID- 2256892 TI - Inheritance of species-specific behaviors in the paradise fish (Macropodus opercularis): a diallel study. AB - Species-specific elements of the paradise fish's ethogram were recorded in one familiar and three different unfamiliar environments, which were designed to model certain features of this species' natural habitat: (1) a densely vegetated home range, (2) a novel open field, (3) a small novel place, and (4) a small novel place with a predator. The inheritance of the behavioral elements was investigated employing a five-times-replicated diallel cross among three inbred strains. A detailed Hayman analysis of variance and a variance-covariance analysis were performed to uncover the genetic architectures of these phenotypes. Additive genetic effects and/or ambidirectional dominance was found to be characteristic of most species-specific behavioral elements studied, suggesting an evolutionary history of stabilizing selection. PMID- 2256893 TI - Courtship behavior and control of reproductive isolation in Drosophila mojavensis: genetic analysis of population hybrids. AB - Drosophila mojavensis from the Sonora region and Baja California show asymmetrical sexual isolation in the laboratory: males from Sonora mate equally frequently with Sonora and Baja females, while the mating success of Baja males with Sonora females is reduced. This failure has been localized to three separate behavioral landmarks occurring during courtship. Genetic analysis was conducted using reciprocal F1 hybrids of Sonora and Baja strains to examine inheritance patterns of the responsible courtship behaviors. Mating success and propensity of F1 males were similar to Sonora males. F1 females mated with males of Sonora and Baja races equally, although mating propensity of F1 females was intermediate between that of Sonora and Baja females. Males of Baja strains presented with F1 females showed a relatively high level of failure at attempted intromission. Genes for mating behaviors are located in the autosomes, but different loci responsible for the sexual isolation appear to act in males and females. PMID- 2256894 TI - The heritability of intelligence in Japan. AB - Japanese data for 543 monozygotic (MZ) twins and 134 dizygotic (DZ) twins tested for intelligence at the age of 12 give correlation coefficients of .782 and .491, respectively, indicating a heritability of .582. Heavier twins at birth have significantly higher IQs at the age of 12, suggesting that prenatal nutrition exerts a significant effect on intelligence. PMID- 2256895 TI - Eysenck's incubation of fear hypothesis: an experimental test. AB - The present experiment was designed to test Eysenck's hypothesis that repeated exposure to an unreinforced CS of brief duration following acquisition of a classical aversive CR may lead to a progressive increase in the strength of that CR, provided that the UCS is intense and the CR has drive-like properties. Using a between-groups design, normal human subjects were given identical classical acquisition trials, followed by extinction trials where CS duration was either 2, 8 or 16 sec. The UCS was of fixed high intensity. Dependent measures were tonic and phasic heart rate and skin conductance. No evidence of incubation was found as a function of CS duration. Nor was there any indication that CS duration differentially affected resistance to extinction. A small number of subjects showed evidence of incubation with heart rate measures during extinction. However, there was no indication that this enhancement was governed by the parameters suggested by Eysenck. UCR amplitude, which showed a positive correspondence with CS-bound activity throughout the trials, did not reliably predict incubation. Problems concerning both the definition and the demonstration of incubation are discussed. PMID- 2256896 TI - Substance abuse and panic-related anxiety: a critical review. AB - The relationship between substance abuse and panic-related anxiety can be divided into two broad areas: the incidence of anxiety disorders in substance abuse patients and the incidence of substance abuse in patients with panic-related anxiety disorders. Studies indicate that approx. 10-40% of alcoholics have a panic-related anxiety disorder, and about 10-20% of anxiety disorder patients abuse alcohol or other drugs. The majority of patients with both an anxiety and alcohol disorder report that anxiety problems preceded alcohol problems. In some cases substance abuse (e.g. cocaine) triggers the onset of panic attacks. Most patients believe that self-medication is efficacious despite the fact that they appear to have a more serious clinical condition (e.g. higher rates of depression). Directions for future research are outlined, including the proposal for a study to examine the effects of an anxiety intervention procedure for anxious alcoholics to reduce relapse rates. PMID- 2256897 TI - A descriptive report of features of initial unexpected panic attacks in minimal and extensive avoiders. AB - Interview data from 162 subjects assigned a diagnosis of panic disorder with or without agoraphobia were analyzed regarding descriptive features of initial panic attacks. The extent to which groups of minimal and extensive avoiders were differentiated by such features was examined. Overall, initial panic attacks were likely to occur at any time of year, and were associated with reported stressors in 72% of the cases. The most frequently reported stressors were somatic in nature. Approximately half of the subjects reported experiencing similar although milder experiences prior to the first panic attack. No differences were found between minimal and extensive avoiders in terms of the presence of others, behavioral response, or location of the first panic attack. Nor did the groups differ with respect to the presence of other anxiety disorders prior to the first panic. However, extensive avoiders tended subsequently to develop additional anxiety disorders moreso than minimal avoiders. Initial panic attack locations were also judged to be more capable of blocking escape action tendencies associated with the fear/panic response in the extensive avoidance group. PMID- 2256898 TI - The role of anxiety and depression in the irritable bowel syndrome. AB - Using a reliable and valid structured diagnostic interview scale (ADIS-R), and patients with careful medical characterization, we found significantly more diagnosable psychopathology, particularly anxiety disorders, among treatment seeking patients with irritable bowel syndrome than among comparable age and sex samples of treatment seeking patients with Inflammatory Bowel Disease. Significant differences were also found on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression between IBS patients and the IBD patients and controls, who did not differ. Comparable levels of psychiatric disorder among parents of probands were found in all three groups. The results are consistent with Latimer's (1983) notion of IBS patients being a subclass of 'neurotics'. PMID- 2256899 TI - Selective processing of threat cues in panic disorder. AB - A computerized Stroop color-naming paradigm was used to investigate attentional biases for selectively processing threat information in panic-disordered patients. Subjects named the colors of neutral words (e.g. TYPICAL), fear words (e.g. PANIC), bodily sensation words (e.g. HEARTBEAT), and catastrophe words (e.g. HEART ATTACK). To control for familiarity with threat concepts, we used clinicians who treat panic disorder as normal control subjects. In contrast to normal controls, panic patients exhibited greater Stroop interference for all threat words, especially those associated with catastrophe. Stroop interference waned during the course of the experiment, thereby indicating habituation to the semantic content of the cues. These findings suggest that panic disorder, like other anxiety disorders, is associated with an attentional bias for processing threatening information. PMID- 2256900 TI - The Maudsley Obsessional-Compulsive Inventory: a psychometric investigation on Chinese normal subjects. AB - The 30-item Maudsley Obsessional-Compulsive Inventory (MOCI) was administered to 183 normal English-speaking Chinese subjects. The inventory achieved modest to relatively low internal consistency as a scale and as four subscales. Three independent dimensions of obsessional complaints interpretable as Perfectionistic and Repetitive Checking, Fear of Contamination, and Doubting Rumination emerged in the factor analysis of item responses. While the first factor corresponded to the Checking component, the second to the Cleaning component, the third was reminiscent of the Doubting, Ruminating and Slowness components. The responses to the MOCI were also explored in their correlations with depression and assertiveness. These results were discussed in in terms of the development of a refined and shortened version of the MOCI and their implications for developing differential treatment models for obsessive-compulsive patients. PMID- 2256901 TI - Components of generalized anxiety: the role of intrusive thoughts vs worry. AB - This study explored possible mechanisms involved with the maintenance of generalized anxiety. While several general anxiety-related variables were investigated, the relationship between worry and intrusive thoughts was of primary interest. We postulated that anxious persons continue to worry in order to avoid recollections of distressing life events. Accordingly, we hypothesized that worry can be distinguished from intrusive thoughts and that the experience of worry would be preferred to intrusive thoughts. Results of a factor analysis indicated that worry and intrusive thought items loaded on separate factors, which supports the hypothesis that worry can be distinguished from intrusive thoughts. The study also examined whether different patterns of worry and intrusive thoughts distinguish between high-anxious, panic, and low-anxious persons and how anxiety sensitivity and self-consciousness are related to generalized anxiety and panic. Finally, we discussed the implications of our results for understanding the psychopathology base of Generalized Anxiety Disorder. PMID- 2256903 TI - Clinical and non-clinical binges. AB - A study was conducted to determine if, and in what respects, clinical binges (reported by bulimic subjects) are different from non-clinical binges (reported by a non-clinical population). Furthermore, the study tested whether the DSM-III R criteria and other variables that are retrospectively claimed to be defining characteristics indeed differentiate binges from non-binge eating episodes. Clinical binges appeared to differ from non-clinical binges as to amount of calories ingested and duration. With respect to subjective experience, clinical and non-clinical binges did not differ. The DSM-III-R criteria for binge eating discriminate clinical and non-clinical binges quite well from non-binges. With the addition of other seemingly important variables, binges are not discriminated better from non-binges than with the DSM-III-R variables alone. It is argued that the difference between pathological binge eating and non-clinical binge eating is mainly a matter of severity. PMID- 2256902 TI - The Mutilation Questionnaire as a predictor of blood/injury fear and fainting. AB - The Mutilation Questionnaire, (MQ) was examined in terms of its psychometric characteristics, its relation to Fear Survey Schedule-II Blood/Injury items, its ability to predict B/I-related fainting, a response common to many B I fearful persons, and its factor structure. In two separate samples of college subjects, females reported greater B/I fear than males, the distributions were positively skewed and negatively kurototic but internal consistency was adequate in both. The MQ correlated 0.75 with five B/I items taken from the FSS-II. While these two scales were comparable in assessing self-reported B/I fear, the MQ was more predictive of fainting. Discriminant analyses of the 30 MQ items in relation to prediction of subjects' faint histories resulted in 77% correct classification of faint history. However, responses to a single question concerning subjects' self assessment of B/I fear was equally as capable of classifying fainting status as the full MQ scale. Responses to the single fear question correlated 0.55 with faint history while MQ scores correlated only 0.45. Factor analyses of the MQ revealed two factors described as 'revulsion of B/I stimuli', accounting for 19% of item variance and 'fear of bodily damage', accounting for 7%. Implications of these results are discussed in terms of the FSS-II, the MQ and alternative means of B/I fear assessment. PMID- 2256904 TI - From the structure to the function of villin, an actin-binding protein of the brush border. AB - Villin, a calcium-regulated actin-binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed by transfecting CV1 cells with a human cDNA encoding wild-type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F-actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli. PMID- 2256905 TI - Cholinesterases preceding major tracts in vertebrate neurogenesis. AB - The role of acetylcholinesterase (AChE) in neurotransmission is well known. But long before synapses are formed in vertebrates, AChE is expressed in young postmitotic neuroblasts that are about to extend the first long tracts. AChE histochemistry can thus be used to map primary steps of brain differentiation. Preceding and possibly inducing AChE in avian brains, the closely related butyrylcholinesterase (BChE) spatially foreshadows AChE-positive cell areas and the course of their axons. In particular, before spinal motor axons grow, their corresponding rostral sclerotomes and myotomes express BChE, and both their neuronal source and myotomal target cells express AChE. Since axon growth has been found inhibited by acetylcholine, it is postulated that both cholinesterases can attract neurite growth cones by neutralizing the inhibitor. Thus, the early expression of both cholinesterases that is at least partially independent from classical cholinergic synaptogenesis, sheds new light on the developmental and medical significance of these enzymes. PMID- 2256907 TI - Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. AB - Cytochrome P450IIE1 is involved in the metabolic activation of many xenobiotics involved with human toxicity. In particular, cellular concentrations of P450IIE1 are significantly induced by the most widely abused drug in our society today, alcohol. As a result, the synthesis and degradation of this form of P450 has significant health consequences. The regulation of the steady-state concentration of P450IIE1 is an extremely complex process. The enzyme is regulated by transcriptional activation, mRNA stabilization, increased mRNA translatability and decreased protein degradation. The principal mechanism which controls the induction process depends on the chemical nature of the inducer, the age, and the nutritional and hormonal status of the animal. There also appear to be significant sex differences in the expression of P450IIE1. It is entirely possible that the regulation of the enzyme concentration under any given set of conditions will involve all of the mechanisms to different extents. PMID- 2256906 TI - Two-way signalling through the LFA-1 lymphocyte adhesion receptor. AB - T lymphocyte recognition of foreign antigens and migration throughout the body require the regulated adhesion of lymphocytes to diverse types of cells and to the extracellular matrix. The lymphocyte adhesion 'receptor' LFA-1, a member of the integrin family, interacts with ICAM-1 and other counter-receptors to mediate adhesion. The LFA-1/ICAM-1 interaction is regulated by signals transmitted from the cytoplasm to the extracellular space. Conversely, LFA-1 transmits signals from the extracellular space to the cytoplasm to regulate T lymphocyte activation. The observed properties of LFA-1 and related adhesion 'receptors' are incorporated into a general model for adhesion during immune surveillance and recognition of foreign antigens. PMID- 2256908 TI - Indomethacin inhibits endocytosis and degradation of insulin. AB - Indomethacin inhibits autophosphorylation of the insulin receptor. The lack of a consensus as to whether phosphorylation of the insulin receptor is necessary for its endocytosis prompted an investigation into the effects of indomethacin on the uptake and subcellular processing of insulin in the perfused rat liver. Indomethacin did not affect total uptake of insulin by the liver, but there was a concentration dependent inhibition of transfer from the plasma membrane to the endosomes (1mM, 32% inhibition; 5mM, 90% inhibition). Compartmental analysis showed the endocytic rate constant to be inhibited by 82% at 5mM indomethacin (0.0084 to 0.0015 sec-1). The similarity between the level of inhibition of autophosphorylation and the inhibition of endocytosis suggest that phosphorylation of the receptor is necessary for endocytosis. Indomethacin at 5mM completely abolished efflux of insulin degradation products from the perfused liver, suggesting that internalisation is an absolute requirement for degradation. PMID- 2256909 TI - Photolabeling of the alpha-neuraminidase/beta-galactosidase complex from human placenta with a photoreactive neuraminidase inhibitor. AB - Photolabeling of the alpha-neuraminidase/beta-galactosidase complex in human placenta (Verheijen, F.W. et al (1987) Eur. J. Biochem. 162, 63-67) was carried out using the radioactive photoprobe, 9-S-(4-azido-3,5-3H-2-nitrophenyl)-5 acetamido-2,6 anhydro-2,3,5,9- tetradeoxy-9- thio-D-glycero-D-galacto-non-2 enonic acid. Two intensely labeled bands at 61 and 46 kD were detected with autoradiography. Labeling of the 46 kD protein was blocked with the inclusion of the surfactant Triton X-100 in the photolysis mixture, indicating a nonspecific, hydrophobic interaction. The 61 kD protein was protected from labeling only when the neuraminidase inhibitor 2,3 dehydro N-acetyl neuraminic acid (1 mM) was present during photolysis. These results suggest that the neuraminidase activity resides among the proteins in the 61 kD molecular weight range comigrating with the lysosomal beta-galactosidase, under denaturing conditions. PMID- 2256911 TI - Stretch activates myosin light chain kinase in arterial smooth muscle. AB - Stretching of porcine carotid arterial muscle increased the phosphorylation of the 20 kDa myosin light chain from 0.23 to 0.68 mol [32P]phosphate/mol light chain, whereas stretching of phorbol dibutyrate treated muscle increased the phosphorylation from 0.30 to 0.91 mol/mol. Two-dimensional gel electrophoresis followed by two-dimensional tryptic phosphopeptide mapping was used to identify the enzyme involved in the stretch-induced phosphorylation. Quantitation of the [32P]phosphate content of the peptides revealed considerable light chain phosphorylation by protein kinase C only in the phorbol dibutyrate treated arterial muscle, whereas most of the light chain phosphorylation was attributable to myosin light chain kinase. Upon stretch of either the untreated or treated muscle, the total increment in [32P]phosphate incorporation into the light chain could be accounted for by peptides characteristic for myosin light chain kinase catalyzed phosphorylation, demonstrating that the stretch-induced phosphorylation is caused by this enzyme exclusively. PMID- 2256910 TI - A vincristine-resistant murine erythroleukemia cell line secretes a differentiation enhancing factor. AB - A clone of vincristine resistant murine erythroleukemia cells V3.17[44], characterized by high sensitivity to terminal erythroid differentiation induced by hexamethylene bisacetamide, secretes into the extracellular medium a protein factor which partially reduces the latent period before commitment and accelerates the expression of the terminal differentiated phenotype in a slow responding murine erythroleukemia N23 cell variant. This differentiation enhancing factor increases the rate of protein kinase C down-regulation which occurs at slower rate during cell differentiation. The activity of the factor is detected either by coculture of the two cell line variants or by addition of conditioned medium from V3.17[44] cells to a culture of N23 cells in the presence of the inducer. In addition to being secreted by V3.17[44] cells, this factor can also be detected in the cytoplasm of both V3.17[44] and N23 cells, associated with a particulate fraction from which it can be released by sonication. PMID- 2256912 TI - Glyoxylic acid prevents NAD+ and NADH depletion in K562 cells cultured at limiting dilution. AB - K562 erythroleukemic cells cultured at low population density in the absence of serum die within 12-24 hours, unless 0.1 mM glyoxylic acid is added to the culture medium. Earlier events, preceding cell death and occurring within 2 hours culture, are: a) a marked drop of both the NAD+/NADH ratio and the NAD+ concentration, which is prevented by 10mM benzamide, b) an increased biosynthesis of NAD+, leading to extensive depletion of cellular ATP. In the presence of 0.1 mM glyoxylic acid the NAD+/NADH ratio as well as their absolute concentrations remain unchanged, while NAD+ biosynthesis is absent. A NAD+/NADH glycohydrolase activity is present in the cell extract, inhibited by 10 mM benzamide and with a higher affinity for NADH than for NAD+. Preservation of a high NAD+/NADH ratio by glyoxylic acid apparently prevents enzyme activity and the related loss of pyridine nucleotides. PMID- 2256913 TI - Antiproliferative effect of interleukin 1 (IL-1) on tumor cells: G0-G1 arrest of a human melanoma cell line by IL-1. AB - Interleukin 1 (IL-1) has been shown to have antiproliferative or cytocidal effects on several tumor cell lines and this effect is closely related to the induction of terminal differentiation of the target tumor cells. In this study we analyzed the antiproliferative effect of recombinant human IL-1 alpha on a human melanoma cell line A375 in relation to cell cycle. Nutrient-starved cells, most of which were in G0 + G1, were stimulated by culturing in fresh medium, causing them to enter S. IL-1 treatment induced a slight decrease in the first cell cycle progression from G0 + G1 to S. In addition IL-1 retarded progression of the cells through G2M and inhibited progression of the second cell cycle from G0 + G1 to S. Therefore we concluded that IL-1 exerts its antiproliferative effect by arresting the cells in G0 + G1. PMID- 2256914 TI - Activin/EDF as an inhibitor of neural differentiation. AB - Activin/EDG, a stimulator of the secretion of follicle stimulating hormone (FSH) from pituitary gland and an inducer of erythroid differentiation for Friend leukemia cells, has since been implicated in a variety of biological roles. Here, we show some novel effects of activin on murine embryonal carcinoma cells (EC cells). First, activin acts as a growth factor on undifferentiated P19 cells, a well characterized EC cell line for the study of mammalian development. Second, activin inhibits the retinoic acid (RA) induced differentiation of P19 cells to neurons and glial cells. The inhibitory effect of activin on neural differentiation, which has yet to be proved in other physiological peptides, is confirmed also on the differentiation of various neuroblastoma cell lines. Our results suggest a possible role of activin as a negative regulator of neural differentiation in mammalian development. PMID- 2256915 TI - Anomeric preference of glucose utilization in human erythrocytes loaded with glucokinase. AB - Human erythrocytes were loaded with homogeneous rat liver glucokinase by an encapsulation method based on hypotonic hemolysis and isotonic resealing. As assayed at 10 mM glucose, glucokinase and hexokinase activities in glucokinase loaded erythrocytes were 218 and 384 nmol/min/gHb, respectively; whereas hexokinase activity in both intact and unloaded red cells, which contain no glucokinase activity, was about 400 nmol/min/gHb. No difference in the rate of lactate production from glucose anomers between intact and unloaded erythrocytes suggested that the encapsulation procedure itself did not affect glucose utilization in red cells. Alpha-anomeric preference in lactate production from glucose was observed in glucokinase-loaded erythrocytes, whereas the beta anomer of glucose was more rapidly utilized than the alpha anomer in intact and unloaded erythrocytes. The results indicate that the step of glucose phosphorylation determines the anomeric preference in glucose utilization by human erythrocytes, since glucokinase and hexokinase are alpha- and beta-preferential, respectively, in glucose phosphorylation. PMID- 2256916 TI - Inhibition of EGF-induced phospholipase C activation in A431 cells by erbstatin, a tyrosine kinase inhibitor. AB - Erbstatin, a tyrosine kinase inhibitor, inhibited epidermal growth factor (EGF) induced inositol phosphate production in cultured A431 cells. However, it did not inhibit ATP-induced inositol phosphate production. Cytosolic but not membrane associated phospholipase C was activated by EGF, and erbstatin inhibited enhancement of the phospholipase C activity in EGF-treated cells. Thus, tyrosine kinase of A431 cells is suggested to be functionally involved in phospholipase C activation. PMID- 2256917 TI - Palmitoyl-L-carnitine, a metabolic intermediate of the fatty acid incorporation pathway in erythrocyte membrane phospholipids. AB - In this paper we report that palmitoyl-L-carnitine can be a metabolic intermediate of the fatty acid incorporation pathway into erythrocyte membrane phosphatidylcholine, and phosphatidylethanolamine. Phospholipid acylation was evaluated by measuring the incorporation of radioactive [1-14C]-palmitoyl-L carnitine in membrane erythrocyte ghost phospholipids in the presence or absence of CoA. CoA highly stimulated the incorporation of [1-14C]-palmitic acid into both the phospholipids examined, although the incorporation was also evident in the absence of added CoA. Incorporation of [1-14C]-palmitic acid into phosphatidylcholine was greater than into phosphatidylethanolamine. 2-Bromo palmitoyl-CoA, an irreversible inhibitor of the erythrocyte carnitine palmitoyltransferase, inhibited the acylation process. PMID- 2256918 TI - The measurement of the rotenone-sensitive NADH cytochrome c reductase activity in mitochondria isolated from minute amount of human skeletal muscle. AB - Mitochondria isolated from minute amounts (100-500 mg) of human skeletal muscle displayed a very high rotenone-resistant NADH cytochrome c reductase activity. Moreover, compared to succinate cytochrome c reductase activity, a low rate of rotenone-sensitive NADH cytochrome c reductase activity was measured when using standard procedures to disrupt mitochondrial membranes. Only a drastic osmotic shock in distillated water as a mean to disrupt mitochondrial membrane was found to strongly increase the actual rate of the rotenone-sensitive activity. This was accompanied by a decrease in the rotenone-insensitive activity. Using such a simple procedure, the NADH cytochrome c reductase was found 70-80% inhibited by rotenone and roughly equivalent to 70-85% of the activity of the succinate cytochrome c reductase. PMID- 2256919 TI - A new guanine-specific reaction for chemical DNA sequencing using m chloroperoxybenzoic acid. PMID- 2256920 TI - Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. AB - A cDNA clone encoding human aldosterone synthase cytochrome P-450 (P-450aldo) has been isolated from a cDNA library derived from human adrenal tumor of a patient suffering from primary aldosteronism. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 3 bp 5'-untranslated region and a 1424 bp 3'-untranslated region to which a poly(A) tract is attached. The nucleotide sequence of P-450aldo cDNA is 93% identical to that of P-450(11) beta cDNA. Catalytic functions of these two P-450s expressed in COS-7 cells are very similar in that both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. However, they are distinctly different from each other in that P 450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone while P-450(11)beta substantially fails to catalyze the reaction to form aldosterone. These results suggest that P-450aldo is a variant of P-450(11)beta, but this enzyme is a different gene product possibly playing a major role in the synthesis of aldosterone at least in a patient suffering from primary aldosteronism. PMID- 2256921 TI - Evidence for involvement of arginyl residue at the catalytic site of penicillin acylase from Escherichia coli. AB - Incubation of penicillin acylase from Escherichia coli with phenylglyoxal or 2,3 butanedione results in enzyme inactivation. Both benzylpenicillin and phenylacetate protect the enzyme against the inactivation, indicating the presence of arginine at or near the catalytic site. The reactions follow pseudofirst order kinetics and the inactivation kinetics indicate the presence of a single essential arginine moiety. PMID- 2256922 TI - Dual promoters and tissue-specific expression of rat transthyretin gene. AB - The rat chromosomal gene for transthyretin was cloned and its dual promoter region was analyzed by primer extension. Semi-quantitative studies by primer extension analysis to determine the transcriptional start sites and their usage in the three tissues have suggested that the rat transthyetin gene has dual promoters: a major proximal promoter which is used in the liver and in the brain but not at all in the kidney, and a minor distal promoter which is totally used in the kidney and significantly in the brain. PMID- 2256923 TI - Transcriptional control of CYP2E1 in the perivenous liver region and during starvation. AB - Previous data indicate that the CYP2E1 gene is transcriptionally activated after birth, but that the expression of ethanol-inducible CYP2E1 protein, hereafter, is regulated by post-transcriptional mechanisms. The constitutive expression of CYP2E1 protein is restricted to the perivenous region of the liver lobule. Here we present results from in situ hybridization and run off experiments indicating that this regioselectivity is caused by a higher rate of gene transcription in the perivenous hepatocytes. We also show that transcription of the CYP2E1 gene is activated by starvation, indicating that also this P450 gene is under transcriptional control under certain physiological conditions. PMID- 2256924 TI - Evidence for the involvement of singlet oxygen in the photodestruction by chloroaluminum phthalocyanine tetrasulfonate. AB - In recent years, choloroaluminum phthalocyanine tetrasulfonate (A1PCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, A1PCTS is going to be under clinical trials of PDT. In this study, in vitro addition of A1PCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (approximately 675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of A1PCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, beta carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the A1PCTS-mediated photodestructive process. PMID- 2256925 TI - Regulation of creatine phosphokinase B activity by protein kinase C. AB - We previously reported that topical application of 12-o-tetradecanoylphorbol-13 acetate to mouse skin causes phosphorylation of epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34). In the accompanying paper, p40 was identified as creatine phosphokinase B. Here we report that both in intact cells and in a cell-free system, phosphorylation of creatine hosphokinase B by protein kinase C resulted in an increase in its ability to catalyze the transfer of the high-energy phosphate of phosphocreatine to ADP, thereby producing ATP. H-7, a specific inhibitor of protein kinase C was found to abolish the increase in enzyme activity. Lineweaver-Burk plot analysis indicated that the increased activity was mostly due to a decreased Km for phosphocreatine. Phosphorylation and activation of creatine phosphokinase B may be a physiological response to maintain ATP balance when a protein kinase C pathway is stimulated. PMID- 2256926 TI - Purification and identification of creatine phosphokinase B as a substrate of protein kinase C in mouse skin in vivo. AB - We previously described epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34) as target proteins of protein kinase C in mouse skin carcinogenesis in vivo. In the present work, p40 was purified from mouse brain by the use of 32P-labeled p40 of BALB/MK-2 cells as a tracer. Following four lines of evidence indicate that p40 is creatine phosphokinase B. 1) The amino acid sequences of all peptide fragments of p40 from mouse brain were located in the primary structure of creatine phosphokinase B. 2) p40 of BALB/MK-2 cells was immunoprecipitated with goat antibody against human creatine phosphokinase B. 3) p40 of BALB/MK-2 cells was absorbed to and eluted from a creatine affinity column. 4) Purified creatine phosphokinase B was phosphorylated in vitro by purified protein kinase C, but not by cAMP-dependent kinase or casein kinase II. PMID- 2256927 TI - Glycolysis and Entner-Doudoroff pathways in Halobacterium halobium: some new observations based on 13C NMR spectroscopy. AB - 13C NMR was used to study glucose metabolism in intact cells of Halobacterium halobium. Spectra of glucose grown cells incubated with [1-13C] glucose indicate the presence of gluconate as the initial product. The existence of glycolytic pathway is also indicated. In the extracts of these cells an NADP dependent glucose dehydrogenase was detected. Galactose grown cells failed to metabolise glucose but exhibited glucose dehydrogenase activity although about 20-50% less than that for glucose grown cells. Possible explanations of these experiments are discussed. PMID- 2256928 TI - Differential accessibility of the tail domain of nuclear lamin A in interphase and mitotic cells. AB - Human autoantibodies reactive against the tail domain exclusive to lamin A and absent from lamin C have been used for immunofluorescence studies on human fibroblast and epithelial cells. These autoantibodies were seen to react on mitotic cells where lamin A is present in a soluble depolymerized form and to react against lamin A in assembled interphase nuclear lamina after in situ extraction of chromatin. Taken together, these results support the suggestion that the tail domain of lamin A may be involved in the putative interaction of lamin A with chromatin. PMID- 2256929 TI - A cytochrome that can pump sodium ion. AB - Previous studies have shown that the bacterium, Vitreoscilla, generates a respiratory-driven delta psi Na+. Two major respiratory electron transport proteins, NADH dehydrogenase (NADH:Quinone oxidoreductase), and cytochrome o terminal oxidase are candidates for the electrogenic Na+ pumping that mediates the delta psi Na+ formation. The NADH oxidase activity of the membranes was enhanced more by Na+ than by Li+. The NADH:Quinone oxidoreductase activity in the respiratory chain was enhanced by Na+ and Li+, whereas the quinol oxidase activity of cytochrome o was enhanced specifically by Na+, and not by Li+, K+, or choline. Purified cytochrome o, reconstituted into Na(+)-loaded liposomes in the right-side-out orientation, catalyzed a net Na+ extrusion when energized with Q1H2(1). In nonloaded inside-out proteoliposomes, this cytochrome catalyzed a net uptake of 22Na+ when energized with ascorbate/TMPD. Both Na(+)-pumping activities were inhibited by CN-. These results are consistent with the Vitreoscilla cytochrome o being a redox-driven Na+ pump. PMID- 2256930 TI - Low-molecular-weight peptides in bone extracts that stimulate osteoblast mitogenesis. AB - Although a majority of regulatory peptides elaborated by neuroendocrine cells are small, i.e., less than 50-60 residues, no low-molecular-weight, bone-derived mitogenic peptides have been described. We have size-fractionated extracts of neonatal mouse calvaria, a rapidly forming bone, and assayed for osteoblast proliferation. Mitogenic peptides with estimated sizes of 1,600, 1,050, and 770 daltons were detected. Their protein nature was demonstrated by the reduction in mitogenic activity following protease treatment. Fibroblast mitogenesis was not stimulated by any of the peptides. These data indicate that there are mitogenic peptides in bone smaller than any previously described locally-derived bone cell growth factor. PMID- 2256931 TI - Identification and characterization of angiotensin II receptor subtypes in rabbit ventricular myocardium. AB - CGP 42 112 A and DuP 753 block [125I]-angiotensin II binding in rabbit ventricular myocardial membranes in a clearly biphasic manner, indicating the existence of high- and low-affinity sites for these highly selective agents. Assays using concentrations of either agent large enough to prevent high-affinity binding show that their respective high-affinity sites are distinct, and each corresponds to the low-affinity site of the other. The two receptor subsets, present in nearly equal proportions, are also distinguishable by their different sensitivities to dithiothreitol. These findings afford strong evidence for the existence of two distinct angiotensin II receptors in rabbit myocardium, corresponding to the A and B subtypes recently described in adrenals. PMID- 2256933 TI - Leukotriene A4 hydrolase: an epoxide hydrolase with peptidase activity. AB - Purified leukotriene A4 hydrolase from human leukocytes is shown to exhibit peptidase activity towards the synthetic substrates alanine-4-nitroanilide and leucine-4-nitroanilide. The enzymatic activity is abolished after heat treatment (70 degrees C, 30 min). At 37 degrees C these substrates are hydrolyzed at a rate of 380 and 130 nmol/mg/min, respectively, and there is no enzyme inhibition during catalysis. Apo-leukotriene A4 hydrolase, obtained by removal of the intrinsic zinc atom, exhibits only a low peptidase activity which can be restored by the addition of stoichiometric amounts of zinc. Reconstitution of the apoenzyme with cobalt results in a peptidase activity which exceeds that of enzyme reactivated with zinc. Preincubation of the native enzyme with leukotriene A4 reduces the peptidase activity. Semipurified preparations of bovine intestinal aminopeptidase and porcine kidney aminopeptidase do not hydrolyze leukotriene A4 into leukotriene B4. PMID- 2256932 TI - Phosphorylation of the human cell proliferation-associated nucleolar protein p120. AB - The human cell proliferation-associated nucleolar protein p120 was found in a variety of human cancer specimens but not in most normal resting cells. Polyclonal antibodies raised against bacterially expressed p120 were used to immunoprecipitate the p120 protein isolated from 32P-labeled HeLa cells. The p120 protein was phosphorylated at serine, threonine and tyrosine residues. A tryptic peptide map showed it contained three labeled peptides. One of these peptides comigrated with a p120 peptide phosphorylated in vitro by casein kinase II. This peptide was phosphorylated in vitro both at Ser-181 and Thr-185. This region is juxtaposed to the epitope site recognized by the anti-p120 monoclonal antibody. PMID- 2256934 TI - Developmental and tissue-specific expression of the rod photoreceptor cGMP-gated ion channel gene. AB - Probes against the retinal cGMP-gated cation channel were generated by PCR amplification of cDNA from rat and bovine retina. Southern and Northern analyses showed that the channel is encoded by a single gene that gives rise to a single mRNA species of 3.2 kb. Low levels of cGMP-gated channel RNA were detected in postnatal day 1 (PN 1) retinas and the amount increased to adult levels over the next two weeks of development. Screening of a number of tissues by Northern blot hybridization and by PCR amplification showed the channel to be expressed by heart and kidney as well as retina, but not by cerebellum, cerebral cortex, liver, muscle, olfactory bulb, spleen, testes or thymus. PMID- 2256935 TI - Primary structure and expression of the Ssc-protein of Salmonella typhimurium. AB - A 1020-bp open reading frame (ORF) was found immediately downstream of the ompH gene of Salmonella typhimurium. This ORF (ORF-36) encodes a moderately hydrophobic protein with 341 amino acid residues (calculated molecular mass, 35,928 Da). The ORF-36 product was detected in minicells. Downstream of ORF-36, another ORF was found. It is highly homologous to the E. coli ORF (ORF-17.4) which precedes the lpx-genes involved in lipid A biosynthesis. ORF-36 is probably analogous to the firA gene of E. coli, the sequence of which has not yet been published. Thus it appears that the enterobacterial ompH and lpx genes are separated only by the ORF-36 and ORF-17.4 genes. We also discuss the data on the function of the ORF-36 protein. On this basis, we suggest that the protein could be called the Ssc protein. PMID- 2256936 TI - Purification and partial characterization of iodothyronine 5'-deiodinase from rat liver microsomes. AB - We have isolated and purified iodothyronine 5'-deiodinase from rat liver microsomes to homogeneity as judged by PAGE and analytical HPLC. The enzyme progressively lost activity after solubilization, and specific activity enhancement was a modest 22-fold, but the final preparation still had substantial activity and was used for molecular characterization. The enzyme had an Mr of 56,000 with a single band in SDS-PAGE, suggesting absence of subunit structure. The high Km, and the GSH-responsive low Km, activities were co-purified, but the low Km enzyme lost GSH-responsiveness upon pretreatment with dithiothreitol (DTT) and urea. The enzyme was strongly inhibited by the iron chelator, alpha,alpha' dipyridyl and showed a broad absorbance band at 410 nm. Spectral analysis with diethylpyrocarbonate (DEPC) revealed 5 histidine residues/mol enzyme, while enzyme activity was inhibited by DEPC in a pseudo-first order process with modification of 1 histidine residue/mol. PMID- 2256937 TI - Inhibition and substrate specificity of yeast delta 22-desaturase. AB - Using yeast microsomes, 23-hydroxysterols were tested as intermediates in the formation of the sterol side delta 22-double bond. No evidence could be found supporting a two-stage mechanism of desaturation via hydroxylation and dehydration. Sterols with various side chains were tested as substrates. Those with alkyl substituents in the 24-alpha position were poor substrates. A series of sterols, including cyclopropyl sterols, were tested as mechanism-based inhibitors without success. Inhibition was observed with an isocyano-sterol. PMID- 2256938 TI - Erythrocyte/HepG2-type glucose transporter is concentrated in cells of blood tissue barriers. AB - In search of possible diverse roles of glucose transporters (GT's), we examined whether any GT's are present in blood-tissue barriers where selective flow of glucose from blood to tissue cells is critically important. We found in rat that the erythrocyte/HepG2-type GT is localized in all the limiting plasma membranes known to serve as blood-tissue barriers, whether the barriers are endothelial type (brain, iris, inner retina, peripheral nerve) or epithelial type (choroid plexus, ciliary body, outer retina, peripheral nerve, placenta), except for plasma membranes in testis and thymus where no appreciable amount of the GT was found. The erythrocyte/HepG2-type GT may play a vital role for the entry of glucose into these firmly guarded tissues. PMID- 2256939 TI - Apolipoprotein B messenger RNA editing is developmentally regulated in pig small intestine: nucleotide comparison of apolipoprotein B editing regions in five species. AB - Apolipoprotein B (apo B) mRNA undergoes a posttranscriptional tissue-specific editing reaction which changes codon 2153 from glutamine (CAA) in apoB-100 mRNA to an in-frame stop codon (UAA) in apoB-48 mRNA. Small intestinal apo B mRNA was found to be predominantly (greater than 90%) unedited in fetal (40-day gestational age) piglets but greater than 95% edited in neonatal, suckling and adult animals. By contrast, both fetal, neonatal and adult pig liver contained greater than 99% unedited, apo B-100 mRNA. The nucleotide sequence spanning the edited region in apo B mRNA was found to be highly conserved. We speculate that the regulation of apo B mRNA editing may be developmentally modulated in pig small intestine. PMID- 2256940 TI - Procollagen type I C-proteinase enhancer is a naturally occurring connective tissue glycoprotein. AB - Using antibodies to the procollagen C-proteinase enhancer of mouse fibroblast culture medium, we have screened by immunoblotting extracts of several post natal mouse and rat tissues for the presence of the enhancer antigen. All rodent connective tissues were relatively rich in enhancer; lower amounts were found in skeletal muscle and heart and essentially no enhancer was detected in kidney, liver or brain. The amounts of enhancer in mouse tendon and calvaria extracts were age related, with highest amounts in 11 and 19 d tendons and in 1 d calvaria the times of rapid growth of these organs. The results suggest that procollagen C proteinase enhancer is a specific connective tissue glycoprotein that is likely to regulate procollagen processing in vivo. PMID- 2256941 TI - A novel epidermal cell differentiation inhibitor (EDIN): purification and characterization from Staphylococcus aureus. AB - A factor inhibiting the calcium-induced terminal differentiation of cultured mouse keratinocytes was purified to homogeneity from the extracellular products of S. aureus E-1 and designated 'epidermal cell differentiation inhibitor' (EDIN). EDIN activity was sensitive to trypsin and heat-labile, suggesting that EDIN is a protein. EDIN gave a single band with a molecular weight of 27,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was found to be a single chain polypeptide, having an isoelectric point higher than 9. The N terminal amino acid sequence of EDIN was determined as A-D-V-K-N-F-T-D-L. EDIN inhibited the differentiation of not only mouse but also human keratinocytes in culture. PMID- 2256942 TI - Changes in the fluidity of the goat sperm plasma membrane in transit from caput to cauda epididymis. AB - Highly purified maturing plasma membranes of goat caput-, corpus- and cauda epididymal spermatozoa, were isolated by an aqueous two-phase polymer method and their fluidity was determined using pyrene and 1,6-diphenyl-1,3,5-hexatriene (DPH) as the membrane lipid probes. Pyrene following partitioning into the lipid phase of the membrane formed excimers at 480 nm and the amount of excimers formed was markedly higher with the immature caput- than the mature cauda-sperm membrane. The fluorescence polarization values obtained with DPH as the lipophilic probe, were lowest in the immature sperm membrane and highest in that of the mature sperm. The data with both the probes are consistent with the view that the lipid phase fluidity of the sperm plasma membrane undergoes significant decrease during the epididymal maturation of the male gametes. PMID- 2256944 TI - Inhibition of calcium-dependent actin gelation by actin-binding protein from platelets. AB - Various proteins related to cell contraction have been extracted from human platelets. Of these, a protein (48K) with the molecular weight of 48,000 and one with the molecular weight of 47,000 (P47) often migrate together with actin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We studied the biochemical characteristics of the 48K protein, purified by actin affinity and DEAE-Sepharose chromatography. The 48K protein did not react with anti-actin antibody or peroxidase-labelled actin. The protein inhibited the calcium dependent gelation of actin. The 48K protein seemed to be a regulatory protein involving cell contraction not identified before. PMID- 2256943 TI - Inactivation of factor C by dimethyl sulfoxide inhibits coagulation of the Carcinoscorpius amoebocyte lysate. AB - The inhibition by dimethyl sulfoxide of the coagulation of the Carcinoscorpius Amoebocyte Lysate was found to be due to the inactivation of Factor C enzyme in the coagulation cascade and not due to the inactivation of proclotting enzyme as earlier reported in studies done on Limulus. Kinetic studies on both purified enzymes revealed that dimethyl sulfoxide completely but reversibly inhibited the activation of Factor C by endotoxins in a non-competitive manner whereas, it did not inhibit, albeit retard the activity of proclotting enzyme. This result also explains why clotting enzyme was shown to be largely unaffected by dimethyl sulfoxide. PMID- 2256945 TI - The amino acid sequence of a ribosome-inactivating protein from Saponaria officinalis seeds. AB - The complete primary structure of saporin SO-6, a ribosome-inactivating protein extracted from Saponaria officinalis seeds, has been determined. The sequence was reconstructed following purification and analysis of peptides obtained after digestion of the protein with different proteolytic agents. The protein is composed of 253 amino acids, corresponding to a molecular weight of 28,621 Da. Comparison of the primary structure of SO-6 with the sequence deduced from cDNA, shows amino acid substitutions in 11 positions, suggesting a tissue-related genetic variability. When the sequence of saporin is compared to those of two related proteins, ricin A chain and trichosanthin, a low degree of similarity (12%) is found; nevertheless some considerations about structure-function relationships and evolution of RIPs are possible. PMID- 2256946 TI - Effects of exogenous growth hormone on insulin action and glucose metabolism in the dwarf 'little' mouse. AB - The in vivo actions of growth hormone (GH) on insulin activity and glucose homeostasis were examined in the GH-deficient Little mouse. The insulin-like action of GH was revealed during glucose tolerance tests on the animals after acute treatment with the hormone and the insulin-antagonistic action was demonstrated in both glucose tolerance tests and insulin tolerance tests on the mice after chronic GH infusion. The primary mechanism of the GH actions is to influence the responses of the target tissues to circulating insulin in vivo. The pancreatic function seems to be of little importance in the alteration of glucose metabolism after acute exposure to GH as no significant change of the levels of plasma insulin was detected. It is concluded that the GH-deficient Little mouse is an ideal laboratory model for the elucidation of the molecular mechanism of the interaction between insulin and GH in the regulation of carbohydrate metabolism. PMID- 2256947 TI - Time profile of hemin aggregation: an analysis. AB - The status of hemin, whether monomeric or aggregated, appears to be a key factor in deciding its biological activity. The molecular basis for the tendency of hemin to aggregate and the factors that regulate it are not yet fully understood. We have investigated the time profile of aggregation of hemin in aqueous solutions and the effect of temperature on the process of aggregation. Aggregation increases with increase in temperature. The time profile data, as monitored by change in absorbance at 398 nm, fits a nonlinear equation with three time constants, suggesting a possibility of three processes. Interestingly, the variation of these three time constants with temperature are different. PMID- 2256948 TI - Role of L-alanine: 4,5-dioxovalerate transaminase in chlorophyll synthesis in Bajra (Pennisetum typhoideum) seedlings. AB - L-alanine:4,5-dioxovalerate transaminase activity and chlorophyll levels were estimated in lead and mercury treated Bajra seedlings. The enzyme activity increased with age upto 2nd day of germination and decreased on consequent days, where as the chlorophyll content increased with age upto 4th day and remained constant on day 5. Both the metals have no effect on L-alanine: 4,5-dioxovalerate transaminase activity but reduced chlorophyll levels. In vitro incubation of the enzyme with metal solutions showed that the enzyme activity was inhibited by mercury, while lead had no effect. Studies on sub-cellular localization of the L alanine:4,5-dioxovalerate transaminase showed that it is present in all fractions. The non-correlation between L-alanine: 4,5-dioxovalerate transaminase activity and chlorophyll synthesis is evident from different activity profiles with age and response to heavy metal treatment in the seedlings. Hence, our results suggest the non-involvement of L-alanine:4,5-dioxovalerate transaminase in chlorophyll synthesis in bajra seedlings. PMID- 2256949 TI - Endothelin activates the vascular renin-angiotensin system in rat mesenteric arteries. AB - The effects of endothelin on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries by measuring vascular renin activity and angiotensin II released into the perfusate. Infusion of endothelin (10(-9)M and 10(-11)M) increased the vascular renin activity and angiotensin II release. Pretreatment with nicardipine (10(-6)M), a calcium channel blocker, significantly suppressed these effects of endothelin. These results suggest that endothelin activates the vascular renin-angiotensin system via intracellular calcium metabolism. Vascular angiotensin II produced by endothelin may modulate the local effect of endothelin on the resistance vessels. PMID- 2256950 TI - Regulation of alpha-ketoglutarate dehydrogenase cooperative properties in substrate binding by thiol-disulfide exchange. AB - The influence of reducing the KGD non-cooperative form by DTT on the KG binding by the enzyme was investigated. The chemical modification of KGD by DEP has revealed that reduction of KGD cysteine residues results in the appearance of the interaction of the dimer active sites upon the enzyme-substrate complex formation. The reduction of 2 SH-groups per KGD subunit: the most reactive one and a buried one--was established to be sufficient for the appearance of KGD cooperative properties in substrate binding as well as for the change in the enzyme activity plots versus substrate concentration. It is suggested that KGD can be regulated by thiol-disulfide exchange in the cell. PMID- 2256951 TI - Calcium modulates the binding of high-mobility-group protein 1 to DNA. AB - Binding of 45Ca2+ to nonhistone protein HMG1 was detected after fixation of the protein to nitrocellulose membrane. The same experiment with HMG1 peptides, derived from HMG1 by protease V8 digestion, allowed to identify the highly glutamic and aspartic C-terminal domain of HMG1 as a 45Ca2(+)-binding region. Measurements of 32P-labeled DNA retention on nitrocellulose filters revealed that in the absence of Ca2+, the affinity of HMG1 for linear DNA decreased upon an increase of pH from 7 to 8.4. However, when Ca2+ was included in the assay buffer, the affinity of HMG1 for DNA remained unchanged between pH 7 to 8.4 and was higher than in the absence of Ca2+. The effect of Ca2+ on HMG1 - DNA interaction was no longer observed upon removal of the C-terminal domain from HMG1. PMID- 2256952 TI - Murine erythroleukemia cell differentiation: possible involvement of a calcium dependent neutral proteinase. AB - Murine erythroleukemia cells contain a single type of calpain classified, on the basis of its calcium requirement, as a type I proteinase. The enzyme is practically inactive at concentrations of calcium below 10 microM and expresses maximal activity in the presence of 0.12-0.15 mM Ca2+. The affinity for Ca2+ cannot be reduced by exposure of the enzyme to conditions known to promote autoproteolysis of calpain. Expression of catalytic activity at lower concentrations of Ca2+, is promoted by the interaction with phospholipid vesicles or plasma membranes. Conditions that promote activation of calpain, induce also the self-inactivation of the enzyme. During terminal differentiation of murine erythroleukemia cells induced by HMBA, the intracellular level of calpain activity undergoes significative reduction. Similar decrease in calpain activity progressively occurs during the loss of sensitivity to HMBA as a result of density growth arrest. PMID- 2256953 TI - Co-operative binding of ribosomal proteins to an erythromycin affinity column. AB - The binding of the E. coli ribosomal proteins L4, L5 and L21 to an erythromycin affinity column has been found to be co-operative. Binding does not occur in the absence of other ribosomal proteins. PMID- 2256954 TI - Enhanced proteolysis of glucose-6-phosphate dehydrogenase in the presence of palmitoyl coenzyme A. AB - Palmitoyl coenzyme A at concentrations below its critical micelle concentration increases the rate of proteolysis of baker's yeast glucose-6-phosphate dehydrogenase by proteinase A in the pH range 4-5. both glucose-6-phosphate and NADP protect glucose-6-phosphate dehydrogenase against proteolysis, but these protective effects are diminished in the presence of palmitoyl coenzyme A. Since palmitoyl coenzyme A is known to dissociate glucose-6-phosphate dehydrogenase into dimers, the results imply that the in vivo half life of glucose-6-phosphate dehydrogenase may be controlled by a process based on the regulation of the oligomeric structure of the enzyme by the collective actions of various molecules, including palmitoyl coenzyme A. PMID- 2256955 TI - Role of fatty acid in the control of protein synthesis in liver cells. AB - Concentrations of oleate (0.2-1 mM) within the physiological range of plasma free fatty acids induced a dose dependent statistically significant inhibition of protein labelling in isolated liver cells. The inhibitory effect was as high as 50% and it was not impeded when long chain fatty acid oxidation was prevented. Experiments carried out with hepatocytes from 48 h fasted rats, incubated in the absence of any exogenous energy source, show that the inhibition of endogenous long chain fatty acid oxidation induced a decreased rate of protein synthesis apparently related to changes in the cellular energy state. It is concluded that fatty acids play a dual role in the regulation of protein synthesis in liver cells: 1. endogenous fatty acids appear to be the main energy fuel for protein synthesis when no other exogenous substrate is present and the carbohydrate stores are low; 2. exogenous fatty acids seem to control protein synthesis by interacting with some key regulatory step. PMID- 2256956 TI - Protease-activated form of protein kinase C with Mr 80,000 generated from rat liver plasma membrane by trypsin-like protease. AB - New type of protease-activated form of protein kinase C was generated from rat liver plasma membrane by action of endogenous trypsin-like protease. The molecular mass was estimated to be about 80,000 by immunoblot analysis which was slightly smaller (approximately 2,000) than that of native protein kinase C. The protein kinase activity was 2-times stimulated by Ca2+ and phospholipid and inhibited by the synthetic peptide derived from the pseudosubstrate region of protein kinase C. This type of activated kinase was produced in purified enzyme system in the absence of either Ca2+ or phospholipid or both. These results suggest that limited proteolysis generating the active form of Mr 80,000 may occur on the inactive form of protein kinase C. PMID- 2256957 TI - Structural dissimilarity in insulin-like growth factor II genes of the rat and the human. AB - A comparison of insulin-like growth factor II(IGFII) genes revealed the lack in the rat genome of a transcriptional system identified in human IGFII gene, h1-h2 h3. Complete deletion was, however, restricted to the h1 region, while the h2 and h3 sequences were conserved in a nearly intact form and in a highly deviated one, respectively. Meanwhile, the human genome contained a region highly homologous to the rE1 sequence, a rat-specific leader exon. These results indicate that the IGFII genes of these species were derived from a common ancestral gene having, together with two other common leader exons, rE2 (h4) and rE3 (h4B), four leader exons, and that the human-specific leader exon h1 sequence was not newly acquired in the human genome but was deleted from the rat genome after speciation. PMID- 2256959 TI - Mutational analysis of the epidermal growth factor-receptor kinase. AB - The biological responses of epidermal growth factor (EGF) are mediated by a surface receptor denoted as the EGF receptor. The EGF receptor possesses intrinsic protein tyrosine kinase activity which is essential for signal transduction. Recent evidence shows that EGF receptor phosphorylates several substances including: phospholipase C-gamma and the GTPase-activating protein (GAP). Moreover, these proteins become associated with the activated receptor in an immunocomplex. Autophosphorylation of the EGF receptor appears to be required for the association with phospholipase C-gamma. Mutational analysis indicates that the intrinsic autophosphorylation sites compete with exogenous substrates for the substrate-binding site in the kinase domain. The ligand-binding site for EGF was analysed using a chimeric receptor approach. Subdomains of the extracellular ligand-binding region of the chicken EGF receptor, which binds EGF with low affinity, were replaced by corresponding regions of the human EGF receptor, which binds EGF with high affinity. On the basis of this analysis, it is concluded that subdomain III of the extracellular domain of the EGF receptor is a major ligand-binding domain. Together, domain I and domain III are able to reconstitute nearly all interactions which bring about high-affinity binding. Growth factor receptors with protein tyrosine kinase (PTK) activity could be envisioned as membrane-associated allosteric enzymes. Unlike water-soluble allosteric enzymes, the configuration of the growth factor receptors dictates that the ligand-binding domain and PTK activity of the receptor molecules are separated by the plasma membrane. Therefore, ligand-induced signal must cross the membrane barrier to activate the PTK function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2256958 TI - The N-terminal sequence of the large proteoglycan of articular cartilage. AB - A peptide with hyaluronic acid-binding properties was isolated from trypsin digests of bovine articular cartilage proteoglycan aggregate. This peptide originated from the N-terminus of the proteoglycan core protein, retained its function of forming complexes with hyaluronate and link protein and contained at least one keratan sulfate chain. Amino acid sequence data demonstrated that the first six amino acid residues of the N-terminus of bovine articular cartilage proteoglycan core protein differed from the same region from the rat chondrosarcoma proteoglycan. Further sequence data indicate areas of considerable sequence homology in the hyaluronic acid-binding regions of proteoglycans from the two species. PMID- 2256960 TI - Regulation of transmembrane signalling elements: transcriptional, post transcriptional and post-translational controls. AB - G-protein-mediated transmembrane signalling is a common motif in biology. The actions of a populous group of G-protein-linked receptors in hormone action, olfaction and vision in vertebrates are examples in which input signals are transferred from a receptor molecule (or photopigment) to an effector unit(s) via G-proteins. The expression and functional status of the receptors, G-proteins, and effectors that constitute these transmembrane signalling systems are regulated physiologically. Altering the abundance, function, or both of these elements provides the means for modulating transmembrane signalling and integration of information among separate pathways. Recent advances in the cell and molecular biology of transmembrane signalling elements provide insight as to the mechanisms by which regulation occurs. Transcriptional control is exemplified by glucocorticoid induction of beta-adrenergic receptor expression. Agonist induced down-regulation of beta-adrenergic receptor mRNA via message destabilization best highlights post-transcriptional control. Examples of post translational control of transmembrane signalling elements include protein phosphorylation, thioldisulphide exchange, and altered rates of protein degradation. Simultaneous analysis of physiological regulation at the levels of the gene, mRNA, and protein provide new opportunities for understanding how information processing extends from the plasma membrane to the genome. PMID- 2256961 TI - The molecular basis of GTP-binding protein interaction with receptors. AB - The molecular basis of the interaction between the visual receptor, rhodopsin, and the rod outer segment GTP-binding protein, transducin or Gt, was studied using a synthetic-peptide-competition approach to elucidate the site(s) on the Gt alpha-subunit (alpha t) involved in high-affinity binding to light-activated rhodopsin (R*). Synthetic peptides based on the amino acid sequence of portions of the molecule that interact with rhodopsin can themselves bind the rhodopsin and thus behave as competitive inhibitors of rhodopsin-G-protein interaction. This blockade was assessed by measuring the ability of peptides to inhibit Gt stabilization of the metarhodopsin II conformation of rhodopsin. Based upon this analysis, two regions near the C-terminal of alpha 1 are important for interaction with R*. PMID- 2256962 TI - Regulation of acetylcholine receptor gene expression by neural factors and electrical activity during motor endplate formation. PMID- 2256963 TI - Indigent children who are denied care in the emergency department. AB - We conducted a six-month prospective study of the diagnoses and outcomes of 588 children who were denied care in our emergency department under a new primary care case management health system for 100,000 indigent patients. The mean patient age was 4.7 years (39% were less than 2 years old). The most common presenting complaints were colds, earaches, rash, vomiting, and diarrhea. Nine percent of children presented for trauma, and 10% had fever of more than 38.2 C. Follow-up was available from the primary care physician for 388 children (66%). Of the 60% of patients who kept their arranged appointment, 42% received antibiotics, 3% were referred for further evaluation, and two children were hospitalized. Follow-up was available from the parents for 125 children (21%). No follow-up information of any kind was available for 111 children (19%), and no follow-up regarding the health of the child was available for 265 children (45%). This last group included 10% with a chief complaint of trauma and 6% with temperature of more than 39 C. Forty-nine percent of patients in this group were less than 2 years old. PMID- 2256964 TI - Prison suicide in England and Wales, 1972-87. AB - The case notes of 295 suicides (98.3% of the total) in prisons in England and Wales between 1972 and 1987 were studied. This period has witnessed an increase in the suicide rate far in excess of the rate of rise in the prison population. The most common method of suicide was by hanging, usually at night. There was a frequent past history of psychiatric treatment and self-injury. People charged or convicted of violent or sexual offences were over-represented, as were those serving life sentences. There was an association between suicide and both guilt for the offence and being charged or convicted of a homicide offence. Some suicides occurred many years after reception into prison. Routine enquiry about previous suicide attempts must be implemented, along with better, ongoing, active communication between staff and inmates. PMID- 2256965 TI - The universal tip. PMID- 2256967 TI - Genetic databanks: new computer link for Japan. PMID- 2256966 TI - Antibiotic treatment of suspected neonatal meningitis. PMID- 2256968 TI - Healers and strangers. Immigrant attitudes toward the physician in America--a relationship in historical perspective. AB - The current wave of immigration to the United States--mostly Asians and Latin Americans--may well be the largest in the 20th century. Many newcomers practice habits of health and hygiene deficient by American standards. Some prefer the shaman to the physician and traditional herb remedies to modern medical therapies. Physicians find themselves practicing at an invisible border separating them from their foreign-born patients, where differences of language and culture can lead to misunderstanding and frustration, impeding a physician's ability to gain cooperation with prescribed therapy. Similar issues faced physicians at the turn of the century. Newly arrived Italians, East European Jews, and Chinese were often ambivalent toward physicians and their therapies. Quacks further undermined the physician's credibility among immigrants. Today, some physicians try collaborating with shamans and herbalists to accommodate patients' cultural preferences. Respect for the customs and taboos of immigrant patients pays dividends in physician effectiveness and efficiency. PMID- 2256969 TI - Sudden infant death syndrome. PMID- 2256970 TI - Topical lignocaine; toxic lignocaine. PMID- 2256972 TI - Motor delay and cerebral palsy. PMID- 2256971 TI - Comparison of one-injection-site peribulbar anesthesia and retrobulbar anesthesia. AB - One hundred patients having elective cataract surgery were evaluated in a prospective, randomized, double-blinded study comparing retrobulbar and peribulbar anesthesia. Patients were divided into two study groups and evaluated on three criteria felt to be critical to intraocular surgery. Results showed that the efficacy of the one-injection-site peribulbar block was similar to that of the retrobulbar block for all three criteria. Because the one-injection-site anesthetic is administered outside the muscle cone, the potential for optic nerve and central nervous system complications should be minimized. PMID- 2256973 TI - Short-term hospitalization for suicidal patients within a crisis intervention service. AB - This article describes management of two cases in a short-term medical/surgical setting developed by a crisis intervention service in a general community hospital. These patients have common links of suicidal threats, ambivalence about psychiatric hospitalization, and noncompliant character structures that lead to a manipulation of the mental health system. Cases selected are representative of a subset of patients who historically don't do well on a regular inpatient unit. We will examine the clinical change during short-term hospitalization, explore psychodynamic issues, and describe the integration within the overall mission of an acute care general hospital. The cost-saving implication for brief hospitalization in a medical/surgical setting for maintaining chronic mental patients in the community is also discussed. PMID- 2256975 TI - After the asylums: The local picture. PMID- 2256974 TI - Oxpentifylline treatment of venous ulcers of the leg. AB - OBJECTIVE: To determine the effect of oxpentifylline on the healing of venous ulcers of the leg. DESIGN: Double blind, randomised, prospective, placebo controlled, parallel group study. SETTING: Four outpatient clinics treating leg ulcers in England and the Republic of Ireland. PATIENTS: 80 Consecutive patients with clinical evidence of venous ulceration of the leg in whom appreciable arterial disease was excluded by the ratio of ankle to brachial systolic pressure being greater than 0.8. INTERVENTIONS: All patients received either oxpentifylline 400 mg three times a day by mouth or a matching placebo for six months (or until their reference ulcer healed if this occurred sooner) in addition to a locally standardised method of compression bandaging. MAIN OUTCOME MEASURES: The primary end point was complete healing of the reference ulcer within six months. The secondary end point was the change in the area of the ulcer over the six month observation period. RESULTS: Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with oxpentifylline and in 12 of the 42 patients treated with a placebo. Life table analysis showed that the proportion of ulcers healed at six months was 64% in the group treated with oxpentifylline compared with 34% in the group treated with a placebo (log rank test chi 2 = 4.78, p = 0.03), which was significant (odds ratio = 1.81, 95% confidence interval 1.20 to 2.71). CONCLUSION: Oxpentifylline used in conjunction with compression bandaging improves the healing of venous ulcers of the leg. PMID- 2256976 TI - Demise of autopsies. PMID- 2256977 TI - Captopril, but not diltiazem, favorably affects the course of early chronic renal disease in rats. AB - The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases. PMID- 2256978 TI - ABC of major trauma. Management of the upper airway. PMID- 2256979 TI - Creutzfeldt-Jakob disease. PMID- 2256980 TI - Human fertilisation and embryology bill goes to report stage. PMID- 2256981 TI - Antihypertensive and adverse biochemical effects of bendrofluazide. PMID- 2256982 TI - Diagnostic paracentesis. PMID- 2256983 TI - Do leukocytes have a role in the cerebral no-reflow phenomenon? PMID- 2256985 TI - Diabetic retinopathy. PMID- 2256984 TI - A place for surgery in arthritic diseases. PMID- 2256986 TI - HIV and granuloma inguinale in Durban. PMID- 2256987 TI - Occupational exposure to nitrous oxide in four hospitals--a comment. PMID- 2256988 TI - Craniotomy drains and bradycardias. PMID- 2256989 TI - Possible Lyme carditis--not definite. PMID- 2256990 TI - Emergency treatment of avulsed incisor teeth. PMID- 2256991 TI - Signs of illness preceding sudden unexpected death in infants. PMID- 2256992 TI - Technetium-99m DTPA renal transplant imaging in the diagnosis of urinoma. PMID- 2256993 TI - Qualitative and quantitative research: the discussion continues. PMID- 2256994 TI - Extramedullary blast crisis in chronic myelogenous leukaemia. PMID- 2256995 TI - Nonantigen-specific tissue localization of monoclonal antibodies. PMID- 2256996 TI - Surgical treatment of thyrotoxic exophthalmos. PMID- 2256997 TI - Pericardial constrictive tissue buffers cardiac transmural pressures. PMID- 2256998 TI - Detecting awareness during general anaesthesia. PMID- 2257000 TI - Prison suicides. PMID- 2256999 TI - Mitochondrial myopathy and anaesthesia. PMID- 2257001 TI - Inhibition of sleep-induced growth hormone secretion: no effect on diabetic control. PMID- 2257003 TI - De-pigmenting skin conditions, cancer, and surgery in Nepal. PMID- 2257002 TI - Hypomagnesaemia and atrial fibrillation in a case of aluminium phosphide poisoning. PMID- 2257004 TI - Methotrexate, liver abnormalities and RA. PMID- 2257005 TI - NSAID associated gastritis and Helicobacter pylori. PMID- 2257006 TI - Perinatal drug abuse. PMID- 2257007 TI - Re: "Pulmonary function as a predictor of coronary heart disease". PMID- 2257008 TI - Informed consent: an unresolved issue. PMID- 2257009 TI - Tuberculosis in Britain. PMID- 2257010 TI - Total audit of preventive practices. PMID- 2257011 TI - Emergency endoscopy is necessary in patients with bleeding oesophageal varices. PMID- 2257012 TI - A rapid and simple method to control hyperglycaemia. PMID- 2257013 TI - Smoking cessation and the GP. PMID- 2257014 TI - Some legal issues relating to passive smoking at the workplace. AB - This paper will discuss some of the current legal issues concerning passive smoking at the workplace. Employers who introduce 'No Smoking' policies must take care in the manner in which they introduce any rules and the extent to which the new rules affect those employees who have always been permitted to smoke at work. Changing the rules in an arbitrary fashion may give rise to claims for breach of contract. Smokers may also sue for constructive dismissal should the new rules be imposed in an unreasonable manner. But employers who have followed a fair procedure may have the right to discipline or finally dismiss any smoker who refuses to accept the new rules. PMID- 2257015 TI - Can I buy a syringe? The availability of needles and syringes to intravenous drug users in Adelaide. PMID- 2257016 TI - Sensitization of multidrug-resistant mouse ascites HD33 and Chinese hamster ovary CHRC5S3 cells by a photoreactive vinblastine derivative, NAPAVIN. AB - We have synthesized a new photoreactive vinblastine derivative, 3-[[[2-amino(4 azido-2-nitrophenyl)ethyl]amino] carbonyl]-O4-deacetyl-3-de-(methoxycarbonyl) vincaleukoblastine (NAPAVIN), which absorbs light at around 450 nm. We report here its effects in vitro on multidrug-resistant mouse HD33 Ehrlich-Lettre ascites cells, on Chinese hamster ovary CHRC5S3 cells, on the corresponding drug sensitive cells, on chemosensitive rat TMA1 mammary carcinoma, and on human SW48 colon carcinoma cells. Cells were incubated with the drug prior to activation by laser light at 457 nm. In Vinca alkaloid-sensitive cells, the short-term effects (30 to 72 h after treatment) of NAPAVIN with and without irradiation on cell proliferation are comparable to those of vinblastine. In drug-resistant cells, NAPAVIN without irradiation reduces the 50% inhibitory concentration 2- to 9 fold, compared with vinblastine. Upon irradiation with an argon laser at 457 nm, the concentration causing 50% inhibition of cell proliferation is further decreased to a total of 9- to 33-fold. Long-term effects (up to 6 wk after treatment) are seen in both sensitive and resistant cells. A single dose of the photoactivated drug causes a 6- to 9-fold larger delay (5 wk) in proliferation, compared with an equal dose of vinblastine. PMID- 2257017 TI - Liver cold storage using UW solution: clinical results in 23 consecutive transplants. PMID- 2257018 TI - Experience with Belzer UW cold storage solution in simultaneous pancreas-kidney transplantation. PMID- 2257021 TI - [The autopsy and AIDS. Evaluation and perspectives]. PMID- 2257019 TI - Secondary metabolites by chemical screening: II. Amycins A and B two novel niphimycin analogs isolated from a high producer strain of elaiophylin and nigericin. AB - Two novel natural niphimycin analogs, amycins A (5) and B (3) were isolated from the culture broth of the Streptomyces sp. DSM 3816 by chemical screening methods. In addition this strain produces the antibiotics niphimycin (4), elaiophylin (2) and nigericin (1). Fermentation, isolation, structure elucidation and biological activity of the amycins are described. PMID- 2257022 TI - [Is it still necessary to perform autopsies in patients who died from AIDS?]. PMID- 2257020 TI - Comparison of Ringer's lactate versus UW solution as flushing solutions assessed in the isolated perfused rat liver. PMID- 2257023 TI - [Bronchoalveolar lavage]. PMID- 2257024 TI - [Cardiac lesions in acquired immunodeficiency syndrome (AIDS). Apropos of an autopsy series of 25 cases]. AB - The pathologic study of the cardiac lesions in 25 persons who died of AIDS were studied from autopsies. Most of these patients were intravenous drug abusers (14 cases). Heart failure was symptomatic and lead to death in 4 cases. This study showed histological abnormalities in 76% of the cases. We observed 12 myocarditis. In 6 cases, pathogenes were found: Toxoplasma gondii (2), Cryptococcus neoformans (2), Candida (1), Aspergillus (1). A lymphocytic myocarditis was observed in 6 hearts. By immunohistochemical technique, we could distinguish 2 toxoplasmic myocarditis, and in 4 cases, solitary cysts in the myocardium without inflammation. The remaining lesions comprised respectively: 3 lymphocytic pericarditis, 2 marastic endocarditis and 1 dilated myocardiopathy. PMID- 2257025 TI - [Malignant primary non-Hodgkin's lymphoma of the central nervous system. Anatomo clinical analysis of 35 cases]. AB - We have recorded 35 primary central nervous system (C.N.S.) lymphomas from 1982 to 1988 in Bordeaux in order to show their increasing frequency, and clinicopathological features. Mean age was 57 (15-81). Only one patient was immunocompromised. Clinical symptoms consisted mostly of focal neurologic deficits (23 cases) and mental disturbance (16 cases). Diagnosis was made on bioptic material (20 cases mostly stereotaxic), surgery (13 cases) or autopsy (2 cases). Lymphoma was localised in the brain with unifocal (50%), multifocal (30%) or diffuse (20%) involvement at computed tomographic scans. Histopathological features were diffuse infiltration of the cerebral tissue with perivascular clustering. Two particular cases were observed: one with mostly a perivascular pattern affecting the white matter of both cerebral hemisphere; another with amyloidosis deposits. According to Working Formulation, histologic types were of intermediate or high grade of malignancy (66%), with 35% large, non cleaved-cell (centroblastic) subtype. Immunochemistry on paraffin sections with UCHL-1, MB-2, LN-1, L-26 showed that 94% were of B-cell nature and only one probably of T-cell origin. PMID- 2257026 TI - [Solitary plasmacytoma of the trachea. Apropos of a case]. AB - A case of solitary plasmacytoma of the trachea is reported. Immunohistochemical study is mandatory to prove a monoclonal immunophenotyping. Research for signs of systemic disease and follow up over a long period of time are indicated. Surgery alone, sometimes followed by irradiation, seem to be the treatment of choice. In most cases, complete resolution is observed. PMID- 2257027 TI - [Broncho-alveolar lavage fluid technique at a central pathologic anatomy and cytology laboratory]. PMID- 2257028 TI - [Breast microcalcifications without palpable tumor detected using mammography. Anatomo-pathologic study technique]. AB - Screening mammograms to detect early non palpable breast cancers will hopefully diminish the breast cancer mortality rate. However, proper pathologic examination of mammographically directed breast biopsies is mandatory. Sampling of a specimen containing microcalcifications should be directed by examination of the specimen radiogram. Frozen section of non palpable foci of microcalcifications is never performed. Thorough localization and sampling of the microcalcified lesions permit the detection of very small cancers usually of the intraductal type. PMID- 2257029 TI - [Cause of opportunistic infection in a renal transplant patient]. PMID- 2257031 TI - [Problems of the living in ultra-deep underground structures from a view point of physiological hygiene]. PMID- 2257030 TI - [Marginal siderosis of the central nervous system]. PMID- 2257033 TI - [Visual hemifield differences in recognition of kanji and hiragana and its relation to hemispheric cerebral asymmetries]. AB - Visual hemifield differences in recognition of kanji and hiragana were studied on forty male right handers. A letter of kanji or hiragana was presented unilaterally to the right or left visual hemifield on a CRT display for 123 msec. A hundred and twenty recognition trials were performed for each subject using 20 well-acquainted kanji, 20 unfamiliar kanji and 20 hiragana. Kanji was more accurately recognized in the left visual hemifield than in the right hemifield. This tendency was more prominent in unfamiliar kanji compared with well acquainted kanji. There were no visual hemifield differences in recognition of hiragana. Learning effects were observed for the right hemifield on kanji and both hemifields on hiragana. The results were discussed in relation to cerebral asymmetries of function. Kanji might be processed in the right cerebral hemisphere as geometric forms. The results on hiragana may be explained by mental set. It is suggested that modes of processing may be different between kanji and hiragana. PMID- 2257032 TI - [A comparative study of % fat and living style on nepalese]. AB - Measurements of %Fat, nutrient intake and maximal aerobic power (MAP) were carried out on Nepalese to clarify the cause of obesity attended with modernization. One hundred thirty-two males (KV) who have a natural living style, 20-84 years of age, in rural district and 237 males who have a living style affected by the rapid urbanization, in surburban district were selected as subjects. The subjects of surburban district were divided into two groups. One of them included 147 farmers (BF) who engage in not mechanized farming, 20-73 years of age. Another group included 90 students and wage laborers (BNF) who go to and from Kathmandu (the capital of Nepal), 20-57 years of age. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The survey for the nutrient intake was carried out by the 24-hour recall method to obtain the individual food consumption using the food models. Measurement of MAP was made indirectly by the modified of Margaria et al (1965). The main results are summarized as follows. 1) Mean %Fat and the appearance rates of obesity in each age group showed high values in following order: BNF greater than BF greater than KV. 2) Mean caloric intake in KV was higher than those in BF and in BNF an almost all age groups and no significant difference was found between BF and BNF in all age groups. 3) No significant differences in mean fat intake and in mean animal fat intake among all groups were found in almost all age groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257034 TI - [Estimation of energy expenditure during walking and jogging by using an electro pedometer]. AB - Using an electro-pedometer which is commercially available, energy expenditure during walking and/or jogging was assessed, and was compared with that obtained by oxygen uptake (VO2). Thirteen male students and 12 female students exercised on 6 minutes duration treadmill tests which velocities were 40, 60, 80, 100, and 120m/min for walking and 100, 120, 140, 160, and 180m/min for jogging, respectively. During exercise, energy expenditure was calculated by VO2 value and respiratory exchange ratio, and was estimated by an electro-pedometer. There was a significant linear relationship between energy expenditures estimated by the pedometer and calculated by VO2 during walking and jogging. To predict energy expenditure more precisely by the electro-pedometer, it is suggested that more precise value of stride should be inputted into the pedometer. In conclusion, the present study showed that commercially available electro-pedometer is able to use for the estimation of energy expenditure with precise validity during walking and/or jogging. PMID- 2257035 TI - [Influences of probe application on the measurement of subcutaneous thickness using A-mode ultrasonography ]. AB - The purpose of the present study was to investigate the effects of the way of probe application on the values of subcutaneous fat thickness by use of A-mode ultrasonography . Subjects were six healthy male adults ranging in age from 19 to 35 years. Scapular, triceps, supra-iliac, abdomen, and thigh were chosen for the measurement sites. Observed values of subcutaneous fat decreased with the increase of pressure at scapular, supra-iliac, and abdomen for relatively fatty subjects, but not for lean subjects. However, the values showed little change at triceps and thigh for all subjects. There was no relation between the pressure of probe and the stability of the value. The values were also influenced by the displacement of the probe on skin. Moreover, it was shown that the difference of the angle between probe and skin influenced the values of subcutaneous fat thickness. A-mode ultrasonography++ has many advantages, if it is properly operated considering the above problems. PMID- 2257036 TI - [Development of a semi-closed underwater breathing apparatus, the "eOBA"]. AB - Nippon Sanso K.K developed a compact semi-closed underwater breathing apparatus, the eOBA. It consists of a mouthpiece, manifold with a purge valve, two spring loaded flexible tubes, a small CO2 absorbent canister (net wt. = 190g), and two compact high pressure bottles (50ccx2: 190kg/cm2: 80%O2, 20%N2) with a regulator which supplies the gas at the constant flow rate of 1.5 l/min and lasts for 10 min. Thus, a counterlung is not incorporated. However, spring-loaded tubes act as a counterlung since its volume increases to 3.5 l when fully inflated. Dives to a depth of 5m are also recommended because of no bypass valve. This new eOBA was tested using the mechanical breathing machine and CO2 supply system to the circuit. For the various combinations of tidal volumes (0.5-2.5 l) and respiratory rates (10-20 breaths/min), the pressure at the mouthpiece, respiratory volume and the CO2 level were continuously monitored. The CO2 absorption rates were then calculated. The thin sloping P-V loops demonstrate that the eOBA is a flow dependent type of apparatus. It was found that the external work of breathing (0.1 kg.m/l at 30 l/min) were allowable. The CO2 absorption rates were sufficient when minute ventilation increased to 30 l/min. Thus, results show that the eOBA must be suitable for shallow and short dives. PMID- 2257037 TI - [Evaluation of a semi-closed underwater breathing apparatus, the "eOBA"]. AB - Semi-closed underwater breathing apparatus has commonly been used among military and commercial divers, but never available for recreational divers because of complicated operations, difficulties of maintenance, and expensiveness. Nippon Sanso K.K. has newly deployed a semi-closed circuit underwater breathing apparatus called the "eOBA". It is especially designed for divers to enjoy shallow (max. 5 m) and short (10 min.) dives. This eOBA was evaluated from manned testing based on physiological requirements for the apparatus. Four male and four female subjects participated in the three test trials. Subjects maintained their position at the depths of 2 m and 4 m for 10 min. and e exercised on the underwater ergometer at the depth of 2.4 m. The pressure at the mouthpiece, tidal volume, breathing rate, the inspired O2 level, CO2 level were monitored on breath by-breath basis. The inspired O2 level ranged from 45% (at exercise) to 60% (at rest) and the inspired CO2 level were kept less than 1.0% in the most cases. The P-V loop indicated relatively little external work of breathing (less than 0.1 kg.m/l) and allowable peak pressures (less than 25cmH2O). Results show that the eOBA meets the standards sufficiently under the test conditions and is a safe apparatus for recreational divers if it is properly used. PMID- 2257038 TI - Phospholipid and phospholipid-protein monolayers at the air/water interface. PMID- 2257040 TI - Advances in clinical electromyography. PMID- 2257039 TI - Photophysics and molecular electronic applications of the rhodopsins. PMID- 2257041 TI - Advances in low vision and blind rehabilitation. PMID- 2257043 TI - Advances in rehabilitation of deaf-blind persons. PMID- 2257042 TI - Issues and strategies in the rehabilitation of hearing impaired persons. PMID- 2257044 TI - Shoulder pain in hemiplegia. PMID- 2257045 TI - Chronic musculoskeletal pain: a cognitive approach to psychophysiologic assessment and intervention. PMID- 2257046 TI - Integrating case management, program evaluation, and marketing for inpatient and outpatient rehabilitation programs. PMID- 2257047 TI - Program evaluation guidelines for the rehabilitation professional. AB - The overall purpose of the present chapter was to provide a set of guidelines to new rehabilitation investigators for conducting program evaluation in the burgeoning field of clinical rehabilitation. The specific objectives were to encourage investigators to develop a research consultation network, consider the benefits of utilizing a theoretical framework in specifying program objectives, assess program implementation, and to discuss the need and methods for ensuring high quality data. There is currently a widening gap in the United States and Canada between rehabilitation professionals who provide clinical services and those who conduct research on the effects of rehabilitation interventions. This is a matter of great concern and consequence. Without a firm commitment to evaluation, clinical rehabilitation practice may ultimately flounder in the mire of conjecture and ad hominem debate characteristic of therapeutic movements that have come and gone (e.g., the human potential movement). It is essential for the life of the discipline that rehabilitation programs be firmly grounded in both humanitarian and scientific principles. PMID- 2257049 TI - Advances in rehabilitation technology. Introduction. PMID- 2257048 TI - The experimental technology of brain transplantation: implications for rehabilitation. PMID- 2257050 TI - Rehabilitation of the stroke patient. PMID- 2257051 TI - The challenge of cardiac rehabilitation. AB - Cardiac rehabilitation has emerged as an integral part of cardiovascular care and an important and exciting area of rehabilitation. Its future will depend on the maintenance of adequate funding sources and demonstration that quality of life or cost/benefit assessments justify the continuance of such programs. Physical activity will remain as the cornerstone of most programs, but it must be integrated with other risk factor modification programs. The practitioner of cardiac rehabilitation will need to recognize the appropriate application of risk factor modification. PMID- 2257053 TI - Detection of early pregnancy factor in fetal sera. AB - Utilizing rosette inhibition test recommended by Morton et al., (Morton H, Tinneberg HR, Rolfe M, Mettier L. Rosette inhibition test: a multicenter investigation of early pregnancy factor in humans, J Reprod Immunol. 1982; 4:251 261) we have examined 44 fetal sera of abortion induced by water bag in the second and third trimester pregnancy, 4 umbilical sera of newborns, and their 48 maternal sera for detecting early pregnancy factor (EPF), which activity was expressed as rosette inhibition titre (RIT). The mean RIT value of EPF in fetal sera was 6.00 +/- 0.31 (SD) during 16-17 weeks of gestation, gradually decreased along with gestational weeks, got to 4.25 +/- 0.25 by term. The mean RITs of EPF activity in maternal sera were 5.86 +/- 0.26 and 5.89 +/- 0.35 during 5-7 weeks and 18-19 weeks, respectively, decreased afterwards, and then fell into nonpregnant range (RIT: 4.00 +/- 0.40) after 31 weeks of gestation. There was a close correlation between RITs of 44 fetal and those of their maternal sera (r = 0.615; P less than 0.001). The results revealed the presence of EPF in fetal serum during gestation. The significance of EPF distribution and its possible role of immunological regulation on survival of semiallogeneic conceptus have thus been discussed. PMID- 2257052 TI - Characterization of immunostimulating complexes (ISCOMS) of HIV-1. AB - HIV-1, strain HTLV-III, propagated in H9 cells and purified by sucrose gradient centrifugation, was used as native antigen source for the preparation of immunostimulating complexes, HIV-iscoms. The major antigen detected in the iscom was the cell-derived HLA-DR, which readily could be removed from the virus lysate by immunosorbent. In the iscoms the HIV structural proteins MA p17, p55 and TM gp41 were identified; SU gp120 was present in only minute amounts in the virus lysate. The iscom particles appeared well preserved after freeze drying with a round shape, approximately 35 nm in diameter, comprising morphological subunits, assembled with icosahedral symmetry. Immunization experiments in mice reflected the antigen content of the iscoms. High antibody response was induced to HLA-DR in non-depleted iscoms. Major humoral responses were observed to the viral structural proteins MA p17, CA p24, p55, and also to TM gp41. A low or negligible antibody response to SU gp120 was induced by the HIV-iscoms. The negligible response was, however, overcome by the addition of recombinant gp160 to the virus lysate prior to formation of iscoms, resulting in a preparation evoking a clear serum antibody to gp160. PMID- 2257054 TI - A murine model of NK cell mediated resorption. AB - There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested. PMID- 2257056 TI - HLA G: at the interface. PMID- 2257055 TI - Morphologic changes in the rat uterus following natural mating and embryo transfer. AB - In order to gain some insight into the putative immune suppression that may be induced at the placental implantation sites, the morphological changes at these sites following natural matings and following the transfer of embryos fertilized in vivo were studied. The only histologic parameter that showed a significant difference was the number of granulated metrial gland (GMG) cells. More GMG cells were present in allogeneic than in syngeneic pregnancies, and more GMG cells were present following embryo transfer into an allogeneic female than following the comparable natural mating. The role of the GMG cells in pregnancy is, however, still unresolved. PMID- 2257057 TI - Atropine sulfate impairs selective parameters of performance in the Morris water maze. AB - Twelve rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze. Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the spatial task was assessed 30 min after treatment with 5, 25, 50, 75, or 100 mg/kg, ip, atropine sulfate or the equivalent volume of saline. There was a significant drug effect on escape latency, swim distance, swim speed and swim path measures of spatial performance. There was no significant drug effect on heading error; atropinized animals initially headed toward the escape platform over the first 12 cm of their swim path. However, treatment with atropine sulfate significantly disrupted the usual, direct swim path used to reach the hidden escape platform. Atropinized animals frequently swam a spiraled or looping pattern to locate the platform. We suggest that cholinergic blockade may significantly disrupt the processing of visual cues which rats use in place navigation tasks. PMID- 2257058 TI - Changes in pyruvate dehydrogenase complex (PDHc) activity and [3H]QNB-receptor binding in rat brain subsequent to intracerebroventricular injection of bromopyruvate. AB - Pyruvate dehydrogenase complex (PDHc), a link between carbohydrate and acetylcholine metabolism, is a regulatory enzyme for glucose and neurotransmitter metabolism in the brain and is reduced in Alzheimer-diseased brain. To study functional consequences of an inhibition of PDHc on muscarinic receptor binding, bromopyruvate, a suicide inhibitor od PDHc, was injected intracerebroventricularly (icv) in rats. Bromopyruvate caused a reduction of PDHc activity in the 3 brain regions examined, however, reaching significance only in the cerebral cortex and the hippocampus and not in the striatum, 24 h after injection. 3, 6, and 12 weeks later, there was a normalization or transiently increased activity, respectively, of PDHc in these brain regions. No changes in concentrations of energy-rich phosphates could be demonstrated in the cerebral cortex 12 weeks after brompyruvate injection. The number of muscarinic receptors was significantly reduced in the cerebral cortex 12 weeks after injection. The data indicate that a transient reduction of brain PDHc activity in vivo is associated with a long-lasting reduction in muscarinic cholinergic receptors. Because comparable changes of PDHc and muscarinic receptors are found in dementia of Alzhemier type, the model of bromopyruvate inhibition of PDHc in rats is suggested to be useful for experimental dementia research. PMID- 2257059 TI - Myorelaxant effect of baclofen injected to the nucleus accumbens septi. AB - The GABAergic modulation in the nucleus accumbens septi (NAS) of muscle tone was investigated in rats using behavioral tests. The GABAB receptor agonist baclofen dose-dependently decreased muscle tone in the wire-mesh and bar holding tests both after local injection into the NAS (1.0 and 2.5 micrograms), and after intraperitoneal administration in a dose of 20 mg/kg. In the Wirth's test haloperidol (5 mg/kg i.p.), produced catalepsy, whereas baclofen (20 mg/kg, i.p.) significantly deteriorated rats' performance. Intraaccumbens microinjections of muscimol, midazolam, nicardipine, as well as peripheral injections of haloperidol and midazolam failed to modify muscle tone in the wire-mesh test. These findings argue against the involvement of GABAA receptors, benzodiazepine receptors, as well as dopaminergic- and calcium channel-related mechanisms in the effect of baclofen. Hence, the muscle relaxant effect of baclofen seems to be also mediated through GABAB receptor sites within the NAS. PMID- 2257060 TI - Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR). AB - 35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer "off" periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease. PMID- 2257062 TI - Reduced luteinizing hormone secretion in women with Parkinson's disease. AB - Plasma luteinizing hormone (LH) levels were significantly lower in 10 postmenopausal women with Parkinson's disease (PD) compared to age-matched controls. The remaining hypophyseal hormones and gonadal steroids were similar in PD patients and in controls, suggesting a selective alteration of hypothalamic dopaminergic mechanisms which regulate LH secretion. PMID- 2257061 TI - Decreased uptake and binding of 11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography. AB - Positron emission tomography of the brain following intravenous injection of (+) (R) and (-) (S) N-[11C-methyl]nicotine showed a marked reduced uptake of both isomers, especially the (R) form, in Alzheimer patients as compared to age matched controls. The significantly larger difference between the uptake values of the (S)- and (R)-enantiomers of 11C-nicotine in Azheimer brains may be of diagnostic value. PMID- 2257063 TI - Treatment of parkinsonian tremor with clozapine. AB - After preliminary observations on 5 psychotic and 7 nonpsychotic parkinsonian patients had shown unexpected impressive beneficial effects of the atypical neuroleptic clozapine on tremor, an open clinical study including 12 patients was started. Under a dosage-range approximately 25-50 mg/day significant reduction of tremor intensity and tremor related functional disability (CURS, Sweet's scale) was achieved. Akinesia was not deteriorated, initial fatigue disappeared spontaneously. Pharmacological mode of action of clozapine's antitremor effect remains unclear. Its broad receptor binding spectrum with strong antiserotonergic properties might here play a major role. PMID- 2257064 TI - Debridement of experimental full-thickness skin burns of rats with enzyme fractions derived from pineapple stem. AB - A limited in vivo study using 12 rats with full-thickness skin burns injuries was carried out. The animals were treated 24 h postburn with two newly discovered enzyme fractions derived from the stem of the pineapple (Ananas comosus). The results indicated that even debridement of the injury could be effected rapidly (within 4 h). Although the details of enzyme formulation and clinical application have yet to be established, these findings clearly suggest that two enzyme fractions from pineapple stem have potential as non-surgical debriding agents. PMID- 2257065 TI - Roles of thromboxane and its inhibitor anisodamine in burn shock. AB - Thromboxane (TXA2) and prostacyclin (PGI2) levels, circulatory platelet aggregate ratios (CPAR), CPK, LDH, GOT, platelet counts, blood viscosity, cortisol and urine epinephrine contents were determined in 42 burned patients who were divided into two groups: Group I control (n = 34) and Group II (n = 8) treated with TXA2 synthesis inhibitor, anisodamine. It was found that in controls, both TXA2 and the TXA2/PGI2 ratio increased significantly. There was no marked difference in PGI2 levels between the two groups. Platelet counts and CPAR decreased, while blood viscosity, CPK, LDH, GOT, cortisol and epinephrine in the controls were all significantly higher than those found in Group II patients. All these findings suggested that the changes of TXA2 and the TXA2/PGI2 ratios played an important role in the haemodynamics and haemorrheology in burn shock. The TXA2 synthesis inhibitor, anisodamine, showed beneficial effects by restoring the haemodynamic and rheological disturbances towards normal by virtue of their ability to induce vascular constriction, platelet aggregation, cellular destruction, destabilization of membranes and release of chemical mediators (including enzymes). Furthermore, at 1-3 days postburn, the levels of CPK, LDH and GOT in controls were higher than those measured at 12 h postburn, but this phenomenon was not marked in the treated group, suggesting that after resuscitation, reperfusion damage had occurred and TXA2 might be responsible for the damage. It is assumed that anisodamine could protect tissues from reperfusion damage. The findings also suggested that anisodamine could quicken the restoration of neuroendocrine disturbance initiated by shock (stress). PMID- 2257066 TI - Domestic burns among children. AB - Out of 338 domestic burn injuries 134 affected children below 16 years of age. The investigation was prospective over a 1-year period. The highest incidence occurred in the age-group 0-2 years and was most often caused by contact, secondly by scalds. The sex ratio girls/boys was 1/1.6. The most vulnerable areas were the hands, head and fingers. Activities related to cooking and in the kitchen caused most of the burns. PMID- 2257067 TI - Suicide attempts by self-immolation--our experience. AB - Of 5934 patients admitted to our Burns' Unit at the Soroka University Hospital, Beer-Sheva, Israel between the years 1965 and 1986, 22 had attempted suicide by fire (0.37 per cent). Seventeen of them (77 per cent) died from their burns. The use of flammable liquids was the most common method of immolation. Fifty per cent of the victims were known to have previous mental disorders. PMID- 2257068 TI - Effects of beta-blockade on energy metabolism following burns. AB - The purpose of this study was to compare the effects of propranolol administered either by i.v. infusion or by prolonged oral administration (4 days) during the first 3 weeks following burns. The resting metabolic rate (RMR) of 10 non infected fasting burned patients (TBSA: 28 per cent, range 18-37 per cent) was determined four times consecutively by indirect calorimetry (open circuit hood system) following: (1) i.v. physiological saline; (2) i.v. propranolol infusion (2 micrograms/kg/min following a bolus of 80 micrograms/kg); (3) oral propranolol (40 mg q.i.d. during 4 +/- 1 days); and (4) in control patients. All patients showed large increases in both RMR (144 +/- 2 per cent of reference values) and in urinary catecholamine excretion (three to four times as compared to control values). The infusion of propranolol induced a significant decrease in RMR to 135 +/- 2 per cent and oral propranolol to 129 +/- 3 per cent of reference values. A decrease in lipid oxidation but no change in carbohydrate and protein oxidation were observed during propranolol administration. It is concluded that the decrease in RMR induced by propranolol was not influenced by the route of administration. The magnitude of the decrease in energy expenditure suggests that beta-adrenergic hyperactivity represents only one of the mediators of the hypermetabolic response to burn injury. PMID- 2257069 TI - Socioeconomic factors and the incidence of hospitalized burn injuries in New England counties, USA. AB - This study demonstrates that readily available socioeconomic data routinely collected by the US Census can be used to estimate the incidence of burn injuries within the 66 counties of the populous six-state New England region of the USA. The burn data were collected during the National Burn Demonstration Project and included New England residents admitted for hospital care of burns sustained between 1 July 1978 and 30 June 1979. Linear regression analysis revealed strong associations between calculated burn rates and a number of socioeconomic variables. Associations with five such variables are described, including per capita income, percentage of persons below poverty level, percentage of residences built prior to 1940, percentage of adults with 16 years or more of education, and percentage of persons moving since 1975 with previous residence in the same county. Estimates of burn incidence for counties, together with a previously reported study at the level of census tracts for a major Standard Metropolitan Statistical Area, can be used to reduce the time and cost of burn injury case reporting by health care providers or case-finding efforts for large population groups, and can be used to predict the effectiveness of social and economic programmes and policies that improve the overall well-being of county populations. PMID- 2257070 TI - Effect of acute burn trauma on reticuloendothelial system phagocytic activity in rats. II: Comparison of uptake of radiolabelled colloid and bacteria. AB - The uptake of radiolabelled colloid or bacteria was compared in normal rats and animals subjected to acute burn trauma. The uptake of colloid by the liver was unaffected by burn trauma, but uptake of the labelled bacteria was reduced. Spleen uptake of both colloid and bacteria was reduced by burn trauma while lung uptake was increased. These data are consistent with the hypothesis that acute burn trauma alters reticuloendothelial system phagocytic activity in the rat towards both inert particles and live bacteria. PMID- 2257071 TI - Burn prevention: the need for a comprehensive approach. AB - Traditionally, burn prevention efforts have been directed at public education and numerous burn prevention campaigns have been undertaken during the past 30 years. How successful have these campaigns been? Contrary to burn mortality, statistical data on burn morbidity are extremely difficult to obtain because little national or international data is available. An analysis of the absolute death rates caused by fire and flames for various countries from 1975 through 1986 seems to indicate that world-wide burn mortality has not decreased. On the contrary, in many countries the rates have increased, whereas in countries like the USA, UK, France and FR Germany, the decrease has been disappointingly low. Furthermore, one wonders if the decrease in mortality rates experienced by these countries is the result of effective prevention programmes or if these could be attributed to advances in technology and improved medical care. Burn prevention campaigns aimed at public education have failed to provide the expected decrease in burn injuries. Education may increase knowledge but does not necessarily lead to behavioural and/or lifestyle change. A restructuring of our burn prevention programmes is needed. Modern techniques of motivational theory must be used to promote public concern and action for individual behaviour change, pertinent legislation and product safety. PMID- 2257072 TI - An investigation of immunological subclass function in burned adults. AB - The serum concentrations of the immunoglobulin subclasses and their functional activity against pneumococcal polysaccharide (PPS) and E. coli antigens have been studied for 15 days in 12 adult burned patients, of whom six were randomly allocated to receive biosynthetic human growth hormone (somatropin) and six to form a control group. The concentrations of the major subclasses, IgG1 and IgG2, fell below their normal ranges as a result of injury by burning but had recovered significantly by the eleventh day of the study. There were no significant changes in the concentrations of the IgG3 and IgG4 subclasses, however, the relative proportions of the four subclasses remained unchanged and were comparable to those found in normal man. Significantly reduced functional activities, compared with normal volunteers, were observed in all the subclasses except IgG1. The activities of the major subclasses during the study were correlated with their serum concentrations and when corrected for their concentrations were comparable to those of normal blood donors. There were no significant increases in concentrations or activity of the subclasses as a result of somatropin administration. It is concluded that patients with moderately sized burns have reduced immunoglobulin function which results from the changes in serum concentration rather than from any qualitative change and that somatropin administration results in no improvement in immunoglobulin function. PMID- 2257073 TI - Scald accidents during water aerosol inhalation in infants. AB - A study of 193 infants admitted for burns over a 4-year period revealed 11 infants (5.7 per cent) had sustained scalds during the process of water aerosol inhalation. The water aerosol inhalation therapy was prescribed for respiratory tract infection and carried out at home using either an electric kettle or a saucepan. It appears that infants are prone to this type of injury because of the difficulty of keeping them still during therapy and their inquisitiveness to explore their surroundings. The resulting scalds added to the morbidity of those children already suffering from respiratory tract infections. These accidents can easily be prevented by the alternative use of a humidifier. PMID- 2257075 TI - Intranasal administration of midazolam to a severely burned child. AB - This report describes the use of intranasally administered midazolam for sedation in a critically ill burned paediatric patient without venous access. Placement of a central venous catheter was successfully carried out following sedation by this method. PMID- 2257074 TI - Rehabilitation of burned patients with bilateral above-knee amputations. AB - Bilateral above the knee amputations occur rarely in the seriously burned population. In a 6-month interval, two patients were treated in our Burn Center whose trauma necessitated bilateral above-knee amputations. This led us to review our experience with such cases. A review of 5018 patients treated over a 28-year period identified six patients over a 20-year period who had bilateral above-knee amputations, four of whom survived. These patients were found to have large and deep burns, concomitant injuries and a number of complications. Recovery was time consuming and costly. Physical therapists were challenged to create adaptations of traditional methods to meet the rehabilitation needs of these patients. The patients who survived remain wheelchair bound and unemployed, but are socially active, appear relatively well adjusted and report themselves satisfied with their lives. During a period of time when technological advances in medicine are ensuring survival of victims of massive trauma, questions are raised concerning the advisability of resuscitation. Knowledge gained in the treatment of these patients who are both burned and have had bilateral above-knee amputations can be reassuring to care providers with limited experience with such massive injury. PMID- 2257076 TI - Sick cell syndrome in a burned patient. AB - The sick cell syndrome is a disorder of the cellular Na+/K+ pump with several causes which include hypoxia, sepsis, hypovolaemia and malnourishment. We report an example of the sick cell syndrome which occurred twice to a patient admitted to our Burn Centre, the first time due to hyponutrition and the second time septicaemia. The striking features of this syndrome were hyponatraemia (less than 130 mmol) despite an increasing sodium intake, a reduced natriuria (less than 20 mmol), a trend to hyperkalaemia and unchanged haematological parameters. Clinically the syndrome was characterized by confusion and hallucinations, and the problem was solved by appropriate treatment of the cause. PMID- 2257077 TI - Transmission of HIV infection by amniotic membrane dressing. PMID- 2257078 TI - Glycolysis and related reactions during cheese manufacture and ripening. AB - Fermentation of lactose to lactic acid by lactic acid bacteria is an essential primary reaction in the manufacture of all cheese varieties. The reduced pH of cheese curd, which reaches 4.5 to 5.2, depending on the variety, affects at least the following characteristics of curd and cheese: syneresis (and hence cheese composition), retention of calcium (which affects cheese texture), retention and activity of coagulant (which influences the extent and type of proteolysis during ripening), the growth of contaminating bacteria. Most (98%) of the lactose in milk is removed in the whey during cheesemaking, either as lactose or lactic acid. The residual lactose in cheese curd is metabolized during the early stages of ripening. During ripening lactic acid is also altered, mainly through the action of nonstarter bacteria. The principal changes are (1) conversion of L lactate to D-lactate such that a racemic mixture exists in most cheeses at the end of ripening; (2) in Swiss-type cheeses, L-lactate is metabolized to propionate, acetate, and CO2, which are responsible for eye formation and contribute to typical flavor; (3) in surface mold, and probably in surface bacterially ripened cheese, lactate is metabolized to CO2 and H2O, which contributes to the increase in pH characteristic of such cheeses and that is responsible for textural changes, (4) in Cheddar and Dutch-type cheeses, some lactate may be oxidized to acetate by Pediococci. Cheese contains a low level of citrate, metabolism of which by Streptococcus diacetylactis leads to the production of diacetyl, which contributes to the flavor and is responsible for the limited eye formation characteristic of such cheeses. PMID- 2257079 TI - Volatiles in packaging materials. AB - The increasing application of complex natural and/or synthetic polymers to food packaging has required definitive information on the characteristics of the finished products. High temperature encountered during the manufacturing process may induce thermal decomposition products that can migrate into the packaged product and cause undesirable flavor. A general methodology for testing polymer odor and odor contributors is discussed in this article with examples representing the odor of a variety of packaging materials. The precursors and the mechanisms of the major volatile components of each packaging material are presented. PMID- 2257080 TI - Antioxidants/antimutagens in food. PMID- 2257081 TI - Aeromicrobiology--a review. AB - This article reviews the presence of microorganisms in air and their sources, the relation of airborne dust and endotoxin, the sources of atmospheric microbial contamination in food-processing plants, the mechanisms of airborne particle deposition, the importance of airborne microbes, the survival of microorganisms in air, methods of air sampling, airborne microbial populations in food processing plants, control of airborne microorganisms in food-processing plants, and the general issue of microorganisms in air and their impact on food safety. The purpose was to bring together scattered information about airborne microorganisms and review their importance in food protection and sanitation. PMID- 2257082 TI - Critical review of isolation, detection, and identification of yeasts from meat products. PMID- 2257083 TI - The Scheele memorial lecture 1989. Drug metabolism in the design and safety evaluation of new drugs. PMID- 2257084 TI - Symposium on characterization of macromolecules used as pharmaceutical excipients. Gothenburg, March 7-9, 1990. Proceedings. PMID- 2257085 TI - Radiobiological speculations on therapeutic total body irradiation. AB - Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or "therapeutic" TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors. PMID- 2257087 TI - New therapeutic strategies in the treatment of murine diseases induced by virus and solid tumors: biology and implications for the potential treatment of human leukemia, AIDS, and solid tumors. AB - Understanding the biology and treatment of various cancers (including leukemia) and immunodeficiency disorders is still an ongoing and experimental process. Animal models have been and continue to be important to this process. This review will focus in on work by ourselves and others that have used murine models assessing the effects in vivo of the Friend virus complex (FVC, composed of a spleen focus forming virus and a murine leukemia helper virus) and solid tumors with metastatic potential in order to evaluate new and innovative therapies. These therapies include radiation, hyperthermia, and newly recognized naturally occurring biomolecules termed cytokines. These cytokines include, but are not limited to, the interferons, the tumor necrosis factors, the interleukins, the hematopoietic colony stimulating factors, lactoferrin and E-type prostaglandins. For example, it has been found that lactoferrin, when administered early enough, prolongs the survival of mice injected, but not yet infected, with the FVC. Of even greater potential usefulness is that mice already infected with the FVC can be completely rescued from death by treatment with split low dosage (150 cGy) total body irradiation. Irradiation treatment was associated with restoration of the T helper to T suppressor cell ratio, natural killer cell activity and marrow proliferative responses to the mitogens PHA and con A which were compromised by the FVC. More recent studies in our laboratory have demonstrated the potential of the interleukins and colony stimulating factors to decrease the metastatic potential of the B16 melanoma and the Lewis Lung Carcinoma cell lines. The cytokines can act in greater than additive fashion and combinations of therapies are possible. This review is meant to increase the awareness of these investigative animal models and the new types of combination therapies that can then be used as the basis for future clinical trials evaluating therapeutic efficacy. PMID- 2257086 TI - Radiation and chemotherapy sensitizers and protectors. AB - Radiosensitizers and radioprotectors are part of the chemical modifier approach to cancer therapy whereby the state of the tumor cells and/or normal tissues are modified such that a therapeutic gain is achieved using conventional radiation or chemotherapy. Radiosensitization can be achieved by the use of oxygen-mimetic compounds, agents that alter DNA sensitivity to irradiation, maneuvers that alter DNA repair processes, and manipulation of tissue oxygenation. Standard chemotherapeutic agents such as cisplatin can be utilized in a manner that optimizes the radiosensitization properties. Protection and sensitization can occur by altering the thiol status of the cell. The chemical modifiers field is both developing novel approaches to cancer treatment and increasing the understanding of basic cancer biology. PMID- 2257088 TI - T-cell receptor gene rearrangements and the diagnosis of human T-cell neoplasms. AB - The rearranging antigen receptor genes of lymphoid cells serve as unique clonal markers of lymphoid neoplasms. Gene rearrangement analysis is a highly sensitive and reproducible tool which is useful in the diagnosis and classification of malignant lymphoma/leukemia. Although clonality can often be determined among B cell neoplasms by virtue of immunoglobulin isotype analysis, no such phenotypic marker of clonality exists for T cells. Therefore, clonality of T lymphoproliferative processes is most readily determined by rearrangement analysis of the T cell antigen receptor genes. The alpha, beta, gamma, and delta genes of the T cell receptor gene family encode heterodimeric surface antigen receptors and undergo rearrangement early in T cell differentiation. Identification of rearrangement of T cell antigen receptor genes provides valuable diagnostic information concerning cellular lineage, clonality and classification of T cell neoplasms. This molecular approach is applicable to the diagnosis of occult disease, relapse, and resolution of diagnostic dilemmas in any type of tissue sample including fluids and needle aspirations. PMID- 2257089 TI - Energy balance, body size, and cancer. AB - Increased energy intake and physical inactivity have been shown to heighten the risk of breast, large bowel, and other cancers. Large body size and fatness, as measured by adult stature, body weight and body mass indices, are positively related to a variety of cancers, including breast, colorectum, prostate, endometrium, kidney, and ovary, as well as to total cancer incidence or mortality in many investigations, although conflicting reports exist. Adult weight gain has also been specifically implicated in a few etiologic studies of breast and large bowel cancer. Furthermore, increased birthweight and childhood stature have been linked to increased risk of leukemia, lymphoma, osteogenic sarcoma, and central nervous system malignancies between infancy and young adulthood. Greater body weight also adversely affects breast cancer survival. These findings are complementary and support a role for positive energy balance in promoting human carcinogenesis. Potential mechanisms are discussed. PMID- 2257090 TI - [Advances in the management of severe arterial hypertension]. AB - This article deals with current concepts about severe hypertension. This is defined by recorded values of more than 20 mmHg above the 97th percentile for weight and height. Exceptionally it is asymptomatic, abut most of the time presents with signs of hypertensive encephalopathy and/or hypertensive cardiopathy, cardiac failure and/or acute pulmonary edema. The most frequent causes in the Hospital Infantil de Mexico Federico Gomez were: diffuse acute glomerulonephritis, segmental renal hypoplasia, renovascular hypertension and end stage renal disease. First of all, on admission in the emergency room, the hypertensive child must be treated with rapid-acting drugs such as calcium channel blockers, sodium nitroprusside or diazoxide. Secondly, quick laboratory examinations as urinalysis, serum electrolytes and BUN must be performed to elaborate a presumptive diagnosis, in order to choice a therapy upon the pathophysiology. According to this thought, furosemide administration is mandatory in acute glomerulonephritis and could be supported by nifedipine. In renal hypoplasia and in renovascular hypertension the use of convertase enzyme inhibitors is indicated in the first place and may be supported by propranolol and/or diuretics. Finally, in hypertension due to end-stage renal disease, peritoneal dialysis with hypertonic solutions or ultrafiltration in chronic hemodialysis program are usually needed. PMID- 2257091 TI - [Perinatal mortality in San Luis Postosi, 1988]. AB - Through participation of ten hospital institutions in the city of San Luis Potosi, which systematically take care of newborns, the present collaborative study was performed; this includes all births during the period from january 1st. to december 31st., 1988. The births taken place at home and other sites such as the "Hospital Materno Infantil" during the last six months, were excluded from the study; they accounted approximately 10%. We registered 17,092 births including 204 mortinates. Based on the upper data, the following chart is given, stating weight as well as gestation rates. Precocious fetal mortality (500 to 999 g)--391.30 by thousand; Precocious fetal mortality (20 to 27 weeks)--140.40 by thousand; Late fetal mortality (1,000 g or more)--9.25 by thousand; Late fetal mortality (28 weeks or more)--9.89 by thousand; Hebdomadal mortality (500 to 999 g)--571.40 by thousand; Hebdomadal mortality (20 to 27 weeks)--159.40 by thousand; Hebdomadal mortality (1,000 g or more)--11.96 by thousand; Hebdomadal mortality (28 weeks or more)--12.62 by thousand; Perinatal mortality (1,000 g or more)--21.10 by thousand; Perinatal mortality (28 weeks or more)--22.38 by thousand. The IMSS sent for registration 8,710 births which accounted 51% of the total. Their data revealed the highest values in all rates. In precocious fetal mortality (products between 20 and 27 weeks), the rate value was 543.9 against 140.4 globally counted. Hebdomadal mortality for this 20 to 27 weeks group showed 730.8 against 159.4 globally reported. In 199 out the 204 mortinates, cause of death was registered; 49.7% of these causes was reported as placental circulation insufficiency and 17.1% as major congenital abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257092 TI - [Clinical and biochemical evaluation of the administration of growth hormone]. AB - Ten children with isolated growth hormone deficiency were treated for 1 year with 0.5 UI/kg week with Somatrem (recombinant human growth hormone), given as intramuscular injections three times weekly. Before treatment the children had a chronological age of 7-12.4 years (mean 10.4 years), with a bone age at least 25% below the chronological age. There was no radiological evidence of an intra or suprasellar mass in any child, and no response to provocative growth hormone tests (with exercise or arginine-insulin injection). Informed written consent for treatment was obtained from the parents of each child. Clinical signs were registered every month; triiodothyronine, thyroxine, thyrotropine, glucose, urea, creatinine, blood cells count, and hemoglobine, glycosylated hemoglobine, glutamic-piruvic and glutamic-oxalacetic transaminases, alkaline phosphatase, anti-human growth hormone and, E. coli antibodies, insulin like growth factor 1, and bone age were assessed every 3 months. The mean height velocity was 0.27 +/- 0.1 cm/month before treatment, and increased throughout treatment to a value of 0.62 +/- 0.16 cm/month after 12 months. Within the first year eight of the 10 children had a height increase of 8.4 +/- 0.98 cm. The other two children showed no significant difference; one of them with a very low socioeconomic status, and the other developed typhoid fever. All of the children showed an advance in bone age, but none reached a bone age appropriate for their chronological age; without modifications in the laboratory parameters. Insulin like growth factor 1 increased in 9 children. Pain at the injection site was the only side effect reported. PMID- 2257093 TI - [Oral rehydration in newborns with dehydration caused by diarrhea]. AB - The clinical experience obtained while treating 43 dehydrated newborns due to diarrhea with oral rehydration solution (ORS) using the formula recommended by the World Health Organization is reported. Of the 43 patients, 26 were severely dehydrated (greater than equal to 10% of weight recovery once rehydrated). The averaged time need to correct the dehydration was 4.7 +/- 2.7 hours, with a average intake of ORS of 26.5 +/- 7.5 mL/kg/hour. Children who were being breastfed continued so during the rehydration period. Two of the patients were hospitalized for intravenous treatment, one was due to persistent vomiting during rehydration and probably due to sepsis, and the other due to necrosing enterocolitis. The oral rehydration therapy was successful in 95% of the newborns included in the study, which proved the method to be safe and adequate for the correction of dehydration due to diarrhea among these patients. Similar experiences are reported in Mexico as well as from other countries, which also suggest the use of this therapeutic procedure in children of this age. PMID- 2257094 TI - [Congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency]. AB - The clinical charts belonging to patients suffering from congenital adrenal hyperplasia secondary to a deficiency of the enzyme 21-hydroxylase seen at the Endocrinology Department during 1978 to 1988 were reviewed. The 34 patients were analyzed for various clinical and biochemical parameters when admitted and during their follow-up. The reason for their consultation, in 73.5% of the cases was due to the presence of ambiguity in their genitalia at the time of their birth. The most frequent clinical variety was the classical or "salt-loser" in 55.8% of the cases. The growth chart analysis showed that those patients who were "salt losers" grew and were categorized in lesser percentiles than those who had the simple variety of the disease. The results are similar to those reported in worldwide literature. A close follow-up with emphasis placed on clinical and laboratory data seems to allow for adequate growth and development of these patients. PMID- 2257095 TI - [Status epilepticus in children. Study of 70 cases]. AB - We presented the experience at the Emergency Unit of the National Institute of Pediatrics with children with Status Epilepticus (SE). This series studied 70 patients, the greatest frequency was seen among infants (55%), followed by preschool children (17%). The most frequent type of SE was generalized tonic clonic (54%) also being the most critical. The simple partial status or epilepsia partialis continua was found to be another frequent variety. In newborns babies the most common type of SE was generalized tonic. Sixty percent originated as acute process, their main causes were central nervous infections, ischemic hypoxic encephalopathy, intracranial hemorrhages and intoxications. The remaining 40% were due to chronic processes, the most important was secondary epilepsy. Among these children the main cause was the irregular use of antiepileptic drugs. Other factors were intercurrent infections with fever, head trauma and hyponatremia. Only 12.8% of the cases were idiopathic. Fifteen percent of the SE were successfully treated with diazepam; 44% with phenytoin plus phenobarbital, in 34.2% we used generalized anesthesia with thiopental. In 33% of the acute cases os SE there were sequelae, there were nine deaths (12.8%) all of them with serious illness of the central nervous system. PMID- 2257096 TI - [Experience with the use of a subcutaneous venous access system in 57 pediatric patients]. AB - Since May of 1983 to December of 1988, 62 subcutaneous venous reservoires were implanted in 57 pediatric patients; 29 were boys and the remaining 28 were girls between the ages of 2 and 18 years. Fifty-one patients had malignant illnesses and seven other pathologies. The reservoir was used for the endovenous administration of cytotoxic chemotherapy and antibiotics, hidration, nutrition, the transfusion of blood product and the extraction of samples for laboratory tests. In our experience the most important complication was the infection of the system, on the average 0.06 episodes of infections occurred for every 100 days per reservoir. Other complications observed were less frequent. In our opinion the subcutaneous reservoir represents an useful tool for the care of the pediatric patients who require a central venous catheter for long periods of time. PMID- 2257097 TI - [Achalasia of the esophagus: modified Heller's esophagomyotomy and floppy Nissen fundoplication, via the abdomen]. AB - Six patients with achalasia of the esophagus were submitted to an abdominal esophagomyotomy which extended two centimeters in width and six to eight centimeters in length, descending one or two centimeters from the esophagealgastric union without having to remove the mucosa in 50% of the esophageal circumference while also performing total funduplication of the floppy Nissen type. The clinical evaluation showed the disappearance of all symptoms. Both the endoscopic as well as the X-rays studies showed the obsence of obstructive symptoms or reflux of any sort. The manometry showed a decrease in the pressure exerted by the inferior esophageal sphincter. No complications arose during or after the surgeries. The results were excellent in all cases and mortality was zero. PMID- 2257098 TI - [Spinal epidural abscess. Diagnosis of a case using nuclear magnetic resonance]. AB - This is a case study of a six year old boy with a previous history of a contuse trauma of the cervical spinal region who later developed fever, stiffening of the neck, and signs of spinal compression. A descending myelography detected a lesion at C4. The Nuclear Magnetic Resonance study of the area showed an anterior epidural mass extending from C5 to T1 which displaced the spinal cord. Surgery revealed an epidural abscess which was drained. The patient received parenteral antibiotic therapy. PMID- 2257099 TI - [General theory of paradigms in health]. AB - In Costa Rica, three sequential health paradigms have been identified over the last 50 years. The first began to develop during the 40's and has been called that of the deficiency diseases, since with a diachronic approach it placed excessive emphasis on malnutrition. The second began in 1970 and it is know a that of the infectious diseases, since through a holistic or synchronic approach, it underlined the importance of infections in high rates of morbidity and mortality. The third and last is the paradigm of the chronic diseases, it appeared in the 80's and is presently in process, doing battle with the chronic ailments, life styles, and environment, and it also utilizes a holistic approach. The recognition of these three paradigms has permitted Costa Rica a rapid advance in improving the health of its population, to the point that with a per capita outlay of $130 (U.S. dollars), it has indices similar to those of the industrialized nations. This particular experience could be useful for other less developed countries that are still applying the paradigm of the deficiency diseases. PMID- 2257100 TI - [Diarrhea associated with Trichomonas hominis]. PMID- 2257101 TI - [Combination prosthesis in an extreme clinical case]. PMID- 2257103 TI - [Orosoluble fosfomycin: a rapid and effective antibiotic]. PMID- 2257102 TI - [Application of Maverick shade guides to a clinical case]. PMID- 2257104 TI - [Fracture of intracanalular dowels]. PMID- 2257106 TI - [Endocanalular dowels and root fractures]. PMID- 2257105 TI - [Evolution of Class II amalgam cavity design for deciduous molars]. PMID- 2257107 TI - [Osteotomy and odontotomy in exodontia of impacted third molars]. PMID- 2257108 TI - [Importance of biopsy examination in dental practice]. PMID- 2257109 TI - [Canal cement in common endodontic use: clinical notes]. PMID- 2257110 TI - [Unity system]. PMID- 2257111 TI - [Analysis of lateral and apical seal characteristics of some endodontic materials]. PMID- 2257112 TI - [Bioceramics in surgical therapy of periodontal osseous defects]. PMID- 2257113 TI - Structure studies of mitomycins. III. Structure of M-83. AB - 7-N-(p-Hydroxyphenyl)mitomycin C* (I), C21H22N4O6.H2O, Mr = 444.45, orthorhombic, P2(1)2(1)2(1), a = 8.056 (2), b = 33.832 (9), c = 7.469 (1) A, V = 2036 (1) A3, Z = 4, Dx = 1.45 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 8.8 cm-1, F(000) = 936, T = 293 K, R = 0.041 for 1923 observed reflections with F greater than 3 sigma (F). Although the overall structure, except the p-hydroxyphenyl group, is similar to mitomycin C, the bond lengths in the quinone ring are significantly influenced by the substituent. The phenyl and quinone rings are nearly planar and the two rings form a dihedral angle of 46.36 (7) degrees. Two quinone O atoms deviate from the least-squares planes of the quinone ring on the same side of the plane. PMID- 2257114 TI - Meat mutagens. PMID- 2257115 TI - The biochemistry of cell death by apoptosis. PMID- 2257116 TI - Hydrolysis of 2-acyl-sn-glycero-3-phosphocholines in guinea pig heart mitochondria. AB - Although both 2-acyl-sn-glycero-3-phosphocholine and 1-acyl-sn-glycero-3 phosphocholine may be produced from phosphatidylcholine hydrolysis, studies on the former have lagged behind that of the latter. In this study a lysophospholipase A2 that hydrolyses 2-acyl-sn-glycero-3-phosphocholine has been characterized in guinea pig heart mitochondria. The lysophospholipase A2 activity was not dependent on Ca2+ and was inhibited differentially by saturated and unsaturated fatty acids. This lysophospholipase A2 activity was able to discriminate among different molecular species of 2-acyl-sn-glycero-3 phosphocholines when they were presented individually or in pairs. The order of decreasing rates of hydrolysis of different molecular species of 2 lysophosphatidylcholines, when the substrates were presented singly, was 18:2 greater than 20:4 greater than 18:1 greater than 16:0. A differential inhibition of the rate of hydrolysis of the individual substrates was observed when the substrates were presented in pairs. The degree of inhibition was dependent on the molar ratio of the mixed substrates. The characteristics of the enzyme suggest that involvement in the selective release of fatty acids from mitochondrial phosphatidylcholine would depend on a high selectivity of phospholipase A1 for different molecular species of phosphatidylcholine. A lysophospholipase A1 activity was also characterized in the mitochondria with a distinct acyl specificity from the lysophospholipase A2. Other characteristics of the two lysophospholipases suggest that the two reactions are not catalysed by the same enzyme. PMID- 2257117 TI - High molecular weight soluble neutral maltase-glucoamylases in the intestine of the suckling rat. AB - Previous work from our laboratory has shown that the intestine of the suckling rat, unlike adult rat intestine, contains abundant quantities of at least two soluble neutral maltase-glucoamylases. These enzymes are related antigenically to membrane-bound maltase-glucoamylase, which predominates in adult intestine, but are either more easily solubilized or occupy a different cellular locus. To study the soluble enzymes further, we attempted their isolation from the intestine of 11-day-old suckling rats. Initial attempts were complicated by proteolytic degradation, despite the addition of phenylmethylsulfonyl fluoride, N ethylmaleimide, leupeptin, pepstatin, and EDTA to buffers used for homogenization and column chromatography. Addition of aprotinin, amastatin, bestatin, and phosphoramidone resulted, however, in the isolation of two stable, high molecular weight maltases (HM1 and HM2). Both enzymes eluted before a papain-solubilized membrane-derived maltase-glucoamylase on Sepharose 4B and were separable by DE-52 and Sepharose 6B - Tris affinity columns. They were further purified on a lentil lectin - Sepharose 4B column. Substrate specificities were almost the same and characteristic of maltase-glucoamylases. Hydrophobic binding properties and pH optima of HM1 and HM2 were also similar. HM1 was resolved by sodium dodecyl sulfate - polyacrylamide gel electrophoresis into approximately equal portions of an endo-beta-N-acetylglucosaminidase H sensitive enzyme of molecular weight (MW) 200,000 and an endo-beta-N-acetylglucosaminidase H resistant but endo-beta acetylglucosaminidase F sensitive enzyme of MW 400,000. In contrast, most of HM2 consisted of a doublet of MW 200,000 - 210,000 that was endo-beta-N acetylglucosaminidase H sensitive. The intestine of the suckling rat, therefore, contains two soluble maltase-glucoamylase fractions, with a major portion of high mannose rather than complex oligosaccharides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257118 TI - Characterization and distribution of bombesin-like peptides in the rat brain and gastrointestinal tract. AB - Extracts of rat brain and gastrointestinal tract, analyzed by reverse-phase high performance liquid chromatography and radioimmunoassay, contained two bombesin like immunoreactivity peaks with similar retention times as porcine gastrin releasing peptide (GRP) and its COOH-terminal decapeptide, neuromedin C or GRP(18 27). However, the GRP-like peptide peak did not elute with exactly the same retention time as porcine GRP. The highest concentration of bombesin-like immunoreactivity was found in extracts of antrum, whereas the lowest was found in whole brain. Neuromedin C was present at lower concentrations than the GRP in antrum, duodenum, and ileum, while similar amounts of each were found in brain. PMID- 2257119 TI - [Effects of the infusion of glucagon on the blood levels of thyroid hormones]. AB - We have attempted to determine if mild hyperglucagonemia induced by exogenous glucagon infusion induces changes of serum thyroid hormone levels. Eleven healthy subjects, overnight fasting, received glucagon infusion (2 mg/90 min i.v.), whereas 5 healthy subjects (control group) received normal saline infusion. In the subjects infused with exogenous glucagon plasma glucagon concentrations increased from 130 +/- 24 pg/ml to 550 +/- 68 pg/ml at the end of infusion. At the same time no significant changes in serum T3, rT3 and T4 levels were found. A significant increase in serum rT3 levels was found 270 min after glucagon infusion withdrawal, whereas serum T4 levels remained unaltered during the whole period. Normal saline infusion failed to induce any variation in control group, however a late (at 6th hour) mild increase of serum rT3 in these subjects resulted comparable to the same increase of glucagon infused subjects. The results from this study suggest that mild increase in plasma glucagonemia, as found in patients with severe illness, does not induce a short-time significant lowering of serum T3 and a simultaneous rise of serum rT3 in normal subjects. PMID- 2257120 TI - Effect of recombinant human TNF on human ovarian cancer cell lines. AB - Ovarian cancer is the second most common gynecologic malignancy. Standard therapeutic approaches to this disease, surgery followed by chemotherapy, have produced response rates of up to 80%. However, the five-year survival rate remains around 30%. Recently, Tumor Necrosis Factor (TNF) has received attention as either an alternative or an associated agent for chemotherapy of ovarian cancer. TNF is known to have direct cytotoxic and cytostatic effects on a variety of transformed cell lines "in vitro". Furthermore, TNF is known to enhance significantly the "in vitro" effects of a class of chemotherapeutic agents, specifically those targeted at DNA topoisomerase II. In this work we have investigated TNF-induced cytotoxicity in four established human epithelial ovarian cancer cell lines: A-2774; SV-626; SKOV-3 and Pa-1. TNF mediated cytotoxic activity was observed in a range of concentrations between 1 U/ml and 10-3 U/ml. A-2774 and SV-626 were the two most sensitive lines, especially when exposed to high concentrations of TNF. PMID- 2257122 TI - Fluorimetric study of intracellular Ca++ homeostasis in isolated rat pancreatic acini. AB - A fluorimetric method for the study of intracellular Ca++ metabolism in rat pancreatic acini is described. Following previous reports on the utilization of the new intracellularly trapped fluorescent dye fura2 in human lymphocytes, the authors point out the relevance of the cellular and fura2 concentration as critical issues for an accurate evaluation of Ca++ homeostasis. A dose-response curve to both carbamoylcholine and cholecystokinin is reported, demonstrating the ability of the cells to respond to hormonal stimulation with a transient Ca++ peak. The almost complete absence of noise in the recorded traces allow to carry out an evaluation of the intracellular mechanism related to Ca++ mobilization with a very high sensitivity. PMID- 2257121 TI - [Differences in potential and content of the mucus in the stomach of the rat with avitaminosis A]. AB - Vitamin A (vit. A) acts in the synthesis of glycoproteins and in cell surface phenomena of epithelia. Since the glycoproteins of gastric mucus and the integrity of gastric cell membranes are components of gastric barrier (GB), vit. A could play a role in GB. Five groups of rats were used: I) rats fed on vit. A deficient diet; II) rats pair-fed plus a daily oral dose of 45 micrograms vit. A; III) normal rats; IV) rats recovered from avitaminosis A (avit. A) after 20 days of daily oral dose of 300 micrograms vit. A; V) rats pair-fed plus a daily oral dose of 45 micrograms vit. A. We measured: 1) transparietal gastric potential difference (PD) in vivo (by means of agar-KCl electrodes); 2) mucus (by binding of Alcian blue): in gastric mucosa; adherent to gastric mucosa; in gastric lumen; 3) dry weight of the stomach. Avit. A induced: i) a decrease of PD and mucus in mucosa and lumen; ii) an increase of mucus adherent to mucosa; iii) an increase of the percentage of dry weight on wet weight. All parameters were normal after recovery from avit. A. Results suggest that avit. A could reduce either mucus synthesis or its erosion. Moreover avit. A might modify mucus structure and sterical configuration of mucosal cells. The alteration of mucosal cell membranes could decrease PD. In conclusion the modifications of some components of rat GB seem specifically caused by avit. A and suggest a protective role of vit. A. PMID- 2257124 TI - [Microbiological profile in water-supply conduits from a clogged well]. AB - This article presents the results of an investigation involving bacterioflora in a water well clogged for the presence of biomass. The water well, placed in a zone near Rome, showed some problems about the water quality and about the extraction of water. The examination of the interior of the pipes showed the presence of biomass. The biomass was examined microscopically and bacteriological analyses were carried out on it. Heterotrophic bacteria were enumerated with three different media by direct count, Pseudomonas sp., yeasts and fungi also by spread plate method. The anaerobic Sulphate Reducing Bacteria were investigated by "Most Probable Number" technique. The results of the analyses showed the presence of protozoa and algae. Moreover high quantity of bacterial flora as heterotrophic bacteria and Pseudomonas sp. were revealed. Sulphate Reducing Bacteria were enumerated in low quantities. Sphaerotilus natans, Actinomyces and Rhodotorula were identified. The clogging problems arose from the presence of filamentous microorganisms as Sphaeroilus natans and Actinomyces sp. When microorganisms of this kind are present in aquifers they can multiply massively if the conditions are favorable. PMID- 2257123 TI - The effect of a novel CCK-antagonist (lorglumide) on human and guinea pig gallbladder strips: a tensiometric study. AB - The effect of a novel CCK-antagonist (lorglumide, CR 1409) was evaluated by "in vitro" tensiometric studies on 16 human (gallstone patients) and 12 guinea pig gallbladder smooth muscle strips. In the animal experiments, increasing doses of lorglumide (0.2-6.5 uM) caused a rightward shift of the dose-response curves of CCK-OP, with an increase of the ED50 from 8.2 nM +/- 1.62 SEM, n = 12; to 100 nM +/- 12, n = 4) without affecting the maximal effect (Emax). Schild plot gave an affinity constant of 7.19. In human gallbladders, the effect of lorglumide was also present (ED50 increased from 47 nM +/- 8 SEM, n = 16; to 300 nM +/- 10 SEM, n = 4) coexisting with a large inter-sample variation for CCK-OP ED50s and maximal contractions, most likely due to the histological changes of the wall in chronic cholecystitis. The affinity constant was similar to that found in animal experiments. We confirm the studies previously reported in animals on the existence of a competitive antagonism of lorglumide on CCK gallbladder receptors. Moreover, our results on gallbladders from gallstone patients show that lorglumide is a highly effective antagonist of CCK-induced contractions despite the presence of chronic cholecystitis. Our study might help for a better comprehension of the role of these new anti-CCK drugs in the treatment of biliary pain. PMID- 2257125 TI - A physical explanation of the lognormality of pollutant concentrations. AB - Investigators in different environmental fields have reported that the concentrations of various measured substances have frequency distributions that are lognormal, or nearly so. That is, when the logarithms of the observed concentrations are plotted as a frequency distribution, the resulting distribution is approximately normal, or Gaussian, over much of the observed range. Examples include radionuclides in soil, pollutants in ambient air, indoor air quality, trace metals in streams, metals in biological tissue, calcium in human remains. The ubiquity of the lognormal distribution in environmental processes is surprising and has not been adequately explained, since common processes in nature (for example, computation of the mean and the analysis of error) usually give rise to distributions that are normal rather than lognormal. This paper takes the first step toward explaining why lognormal distributions can arise naturally from certain physical processes that are analogous to those found in the environment. In this paper, these processes are treated mathematically, and the results are illustrated in a laboratory beaker experiment that is simulated on the computer. PMID- 2257126 TI - Numerical simulation of the thermal destruction of some chlorinated C1 and C2 hydrocarbons. AB - We have numerically modeled the breakdown of small quantities of several chlorinated hydrocarbons (CH3Cl, CH2Cl2, CHCl3, CCl4, C2H3Cl, and C2H5Cl) in a lean mixture of combustion products between 800 and 1480 K. This simulates the fate of poorly atomized waste in a liquid-injection incinerator. Kinetics calculations were performed using the CHEMKIN and SENKIN programs, with a reaction mechanism that was developed at Louisiana State University to model flat flame burner experiments. A 99.99-percent destruction efficiency was attained in one second at temperatures ranging from 1280 to 960 K, with CCl4 requiring the highest temperature for destruction and C2H5Cl the lowest. For all compounds except C2H5Cl, there was a range of temperatures at which byproducts accounted for several percent of the elemental chlorine at the outlet. The more heavily chlorinated compounds formed more byproducts even though the amount of elemental chlorine was the same in all cases. The sensitivity of results to residence time, equivalence ratio, temperature profile, and the presence of additional chlorine, was examined for the case of CHCl3. PMID- 2257127 TI - Recent advances in solid-phase peptide synthesis and preparation of antibodies to synthetic peptides. AB - Peptides prepared by the solid-phase peptide synthesis (SPPS) approach are used increasingly in biological research, for instance to elicit anti-peptide antibodies that will recognize the intact, cognate protein. Recent advances in SPPS are reviewed, including the use of new coupling reagents, new methods for evaluating peptide purity and new techniques of automated and multiple peptide synthesis. Methods for enhancing peptide immunogenicity are discussed such as the use of adjuvants and liposomes, and of synthetic branched polypeptides as carriers. PMID- 2257128 TI - Integration, amplification and stability of plasmid sequences in CHO cell cultures. PMID- 2257129 TI - Antibody response to pertussis toxin and filamentous haemagglutinin in NIH mice immunized with the International Standard for Pertussis Vaccine. AB - The antibody response to filamentous haemagglutinin and pertussis toxin was studied in N:NIH mice vaccinated according to the WHO recommendations for potency test with the International Standard for Pertussis Vaccine (ISPV). Some of the vaccinated animals were challenged intracerebrally on day 14. All animals, whether challenged or not, were bled on days 7, 14, 21, 28 and 35 after immunization. The relationship between anti-PT and anti-FHA antibodies measured by ELISA and protection from intracerebral challenge was examined. All those mice with anti-PT titres on day 14 higher than 43 EU/ml survived challenge. No relationship was found between anti-FHA antibodies and survival. Anti-PT titres on day 14 below 43 EU/ml were related to the days of survival after challenge; a linear regression curve of y = 13 + 2.4x, with a correlation coefficient r = 0.61 was found. Anti-PT antibodies seem to play an important role in protection when animals are challenged intracerebrally, as is the case in the standard potency test for pertussis vaccine. PMID- 2257130 TI - Acellular and whole cell pertussis vaccines protect against the lethal effects of intracerebral challenge by two different T-cell dependent humoral routes. AB - Athymic (nu/nu) and euthymic (+/nu) BALB/c mice were immunized with a whole cell pertussis vaccine or with an acellular vaccine which contained detoxified pertussis toxin (PT) and filamentous hemagglutinin (FHA). Only the euthymic mice were protected against intracerebral challenge with virulent Bordetella pertussis which implies involvement of T-cells. As a cell transfer from mice immunized with whole cell or acellular vaccine prior to the challenge did not protect naive euthymic recipients, cellular immunity seems to be non-protective as an effector mechanism. Mice could be protected passively against a challenge by administration of immune sera. Therefore, T-cell dependent humoral immune responses to B. pertussis appear to be crucial for protection. The humoral response was further studied with athymic and euthymic mice. In euthymic mice the whole cell vaccine induced antibodies to FHA, pililipopolysaccharides (LPS) and an outer membrane protein (OMP) preparation, whereas the acellular vaccine induced antibodies to PT, FHA and OMP. Both IgM and IgG could be detected. From the nude mice only those immunized with the whole cell vaccine showed an antibody response which consisted of low titres of IgM directed to LPS. Sera from both +/nu and nu/nu mice immunized with the whole cell vaccine were bactericidal in vitro. These data demonstrate that in the mouse model protection to intracerebral challenge with B. pertussis is T-cell dependent as is the humoral response to PT, FHA, OMP and pili. The T-independent B-cell activation by the whole cell preparation is due to the presence of LPS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257131 TI - In vitro tests for the measurement of veterinary clostridial toxins, toxoids and antisera. I. Titration of Clostridium septicum toxins and antitoxins in cell culture. AB - The assay of Clostridium septicum antitoxin currently requires the inoculation of test mixtures intravenously into mice or intradermally into guinea-pig skin. An alternative indicator system based on the use of cell cultures is described. Evidence is presented to show that the toxins detected by the in vivo and in vitro indicators are indistinguishable in terms of molecular weight, charge and hydrophobicity and that there is a close agreement between the two methods of titration. Cell culture indicators are more sensitive than their in vivo counterparts, permitting detection of substantially lower titres than is possible using in vivo indicators. It is suggested that cell culture indicators may prove useful for the titration of Cl septicum antitoxin in sera from vaccine field trials and potency tests. Cell culture methods could also be used for the potency testing of antitoxin preparations. PMID- 2257132 TI - Heterologous protein expression by transimmortalized differentiated liver cell lines derived from transgenic mice (hepatomas/alpha 1 antitrypsin/ONC mouse). AB - A number of therapeutic plasma proteins are synthesized by human hepatocytes. Since many of these proteins undergo liver-specific post-translational modifications which are required for full biological activity, it may therefore be necessary to develop hepatocyte-based expression systems for their production. Using transgenic mice we have developed a transimmortalisation technique for the isolation of differentiated hepatic cell lines, already engineered to secrete human alpha 1 antitrypsin (alpha 1 AT), a plasma protein which is produced mainly in liver cells. This was achieved by co-expression of the mouse c-myc proto oncogene and a genomic copy of the human alpha 1 AT gene, both under the control of the human alpha 1 AT promoter. Transgenic mice carrying this construct developed hepatomas producing human alpha 1 AT. Under defined culture conditions, cell lines secreting active alpha 1 AT were derived from these tumours. These cells maintain a differentiated hepatic phenotype and continue to secrete human alpha 1 AT for at least 40 generations. PMID- 2257133 TI - Methods for screening the naturally acquired and vaccine-induced immunity to the measles virus. AB - Since the measles, mumps and rubella (MMR) vaccine was introduced into Sweden in 1982, a yearly evaluation of the immunity patterns and sero-conversion rates in 12-year-old children has been carried out. Since 1977, about half of the pre school children have been vaccinated against measles. This study includes two study groups. (1) 145 selected pre- and post-vaccination samples tested by the haemolysis-in-gel (HIG) technique and the neutralization test (NT). The selection was made from 1298 12-year-old schoolchildren in 1986 and 1987, whose pre vaccination sera had shown negative or borderline reactions to the HIG technique. (2) Consecutive pre- and post-vaccination samples obtained from 190 vaccinees in 1988 and 1989. These samples were studied by an enzyme-linked, immunosorbent assay (ELISA) and compared to the NT. The NT and the HIG tests yielded congruent results in early post-vaccination sera from children susceptible to measles prior to vaccination. In late post-vaccination samples, the NT and the HIG tests were discordant, up to 25% of the NT-positive samples being negative by the HIG technique. In no instance did the ELISA produce discrepant results, compared with those of the NT. With both this assays significantly lower antibody levels were detected in late post-vaccination sera (8-11 years) compared to early post vaccination samples (P less than 0.001) or to sera obtained after natural infection. PMID- 2257134 TI - Methods for screening the naturally acquired and vaccine-induced immunity to the mumps virus. AB - Since the introduction of the measles, mumps and rubella (MMR) vaccine in Sweden in 1982, a yearly evaluation of the immunity pattern and seroconversion rate of 12-year-old children has been carried out. To be able to realize large-scale, follow-up studies, techniques have to be used which are not too labour-intensive and time-consuming but are sensitive enough to detect past immunity and post vaccination titres. We report tests with haemolysis-in-gel (HIG) technique and an enzyme-linked, immunosorbent assay (ELISA) compared with neutralization (NT) for the detection of mumps antibodies. This study comprises 226 paired serum samples obtained between 1985 and 1989. One hundred and forty-one of the paired samples had been selected because they had given negative or borderline readings, using HIG technique. The remaining samples were consecutive pre- and post-vaccination sera obtained in 1989 from 85 vaccinees from one area in Sweden. HIG technique gave both false positive and false negative readings, compared with NT as also the false positive sera were detected. Non-inactivated sera could not be used in the NT test against mumps virus, owing to unspecific NT reactions. No differences between non-inactivated and inactivated sera by NT were seen, as against other paramyxoviruses. Cross-reactivity between mumps and parainfluenzae in NT tests was not demonstrated. The ELISA test proved more reliable and specific than HIG and was more sensitive than NT. Some post-vaccination sera from vaccinees who failed to seroconvert by NT contained high levels of mumps antibody detectable by the ELISA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257135 TI - Stability of a gene recombinant: what does it mean and how to check for it? PMID- 2257136 TI - Immunostaining technique for rapid detection of glycosphingolipids with enzymatically labeled probes. AB - Rapid detection of antibody binding to glycolipid is achieved using an enzymatically labeled probe followed by blotting substrate onto the high performance thin-layer chromatogram. PMID- 2257137 TI - Influence of SDS and methanol on protein electrotransfer to Immobilon P membranes in semidry blot systems. PMID- 2257138 TI - Precise, easy measurement of glass pipet tips for microinjection or electrophysiology. AB - We describe a simple procedure to measure precisely the tip diameter of glass micropipets. This procedure can improve the precision of microinjection and some electrophysiological measurements due to their extreme sensitivity to the pipet's exact geometric dimensions. The technique is nondestructive and readily carried out as a brief, extra step in these applications. Digital measurements of the threshold pressures for gas bubbling from (gas filled) pipets submerged in methanol were used to calculate the corresponding inner tip diameters using the LaPlace equation. Direct measurements of the inner tip diameters (from 0.2-5.0 mu) using scanning electron microscopy confirmed the validity of this indirect, simple procedure. PMID- 2257139 TI - Method for the direct detection of both orientations of an insert in M13. PMID- 2257140 TI - Analysis of an acidic polysaccharide by electrophoretic transfer to nitrocellulose and immunostaining. PMID- 2257141 TI - A simple method to facilitate the separation of plasmid DNA. PMID- 2257142 TI - Preparation of a disposable homogenizer for microcentrifuge tubes. PMID- 2257143 TI - Simultaneous visualization of neuronal protein and receptor mRNA. AB - We describe a combined immunocytochemistry/in situ hybridization technique which allows for the simultaneous localization of protein and mRNA in a single cell. We have carried out these studies either on non-innervated skeletal myotubes or on myotubes which we have innervated with spinal cord explants or ciliary neurons. Our methods allowed us to detect acetylcholine receptor gene mRNA sequences which are expressed in low abundance within the cells and to determine the intracellular and intranuclear domains where these sequences are concentrated, as well as to identify neurons and their processes. The isotopic detection of RNA in combination with fluorescence microscopy produces high-resolution double-label images, with little background and good preservation of morphology, providing a powerful tool for detection of gene expression and protein content at the single cell level. PMID- 2257144 TI - A new cellular model of response to estrogens: a bioluminescent test to characterize (anti) estrogen molecules. AB - With the aim of quickly and easily characterizing new estrogen or anti-estrogen molecules, we developed a cellular model in which estrogenic action can be detected by bioluminescence. This model is based on MCF-7 cells stably transfected with a receptor gene which allows expression of the firefly luciferase enzyme under control of the estrogen regulatory element of the Xenopus vitellogenin A2 gene. A stably transfected cell line (cultured for more than eight months without loss of the chimeric estrogenic response) was established by cotransfection of a neomycin resistance gene and cloning under selective pressure. Subcloning luminescent clones was accomplished by using a single-photon detecting camera. This cellular model allowed the study of an estrogenic activity either in whole-cell or in cell-free experiments by detection of the induced luciferase. Estradiol induced the luciferase activity in a dose-dependent manner at subnanomolar concentrations. The induced luciferase activity reached a maximum level as early as 24 hours after the cells were incubated with estradiol. The antiestrogen 4-hydroxy-tamoxifen inhibited the luciferase activity induced by estradiol. The cross-reactivity of ligands, such as dexamethasone, progesterone, testosterone, aldosterone, calcitriol, oxysterol and retinoic acid, were also studied, showing an estradiol specificity for a 24-hour incubation time. PMID- 2257145 TI - A comparison of UV cross-linking and vacuum baking for nucleic acid immobilization and retention. AB - The effectiveness of UV cross-linking and in vacuo baking for the immobilization and retention of DNA to various solid supports was investigated. Optimal immobilization treatments for supported and unsupported nitrocellulose and nylon membranes were: UV cross-linking at 254 nm with an exposure of 120 milliJoules/cm2, or baking in vacuo for two hours at 80 degrees C. UV-immobilized nitrocellulose-based membranes showed no increase in sensitivity when compared to baked membranes. An increase in sensitivity was observed for UV-immobilized nylon membranes as compared with baked nylon membranes in some instances, although this varied within lots of the membranes tested. Repeated strippings and heterologous reprobings resulted in loss of target DNA from UV-immobilized nylon membranes as compared to baked nylon membranes. Loss of target DNA from UV-immobilized nitrocellulose-based membranes due to repeated strippings and reprobings was even more pronounced. In vacuo baking of supported and unsupported nitrocellulose and nylon membranes was more effective for immobilization, and more importantly, for retention of target DNA through many reprobings of the same blot. PMID- 2257146 TI - Electrophoresis of DNA fragments in gels from acrylamide-rich copolymers. AB - Two polyacrylamide-rich, non-toxic, gelable copolymers have been developed to facilitate the formation of user-cast electrophoresis gels. Gel formation is accomplished with dithiothreitol as the chemical cross-linking agent. The higher molecular weight copolymer is suitable for casting gels of copolymer concentration less than or equal to 8%. Gels of 3% concentration are excellent for resolving dsDNA fragments up to approximately 3000 base pairs. Because the cross-linking chemistry is not thwarted by the presence of urea, it is also possible to cast denaturing gels with these copolymers. PMID- 2257147 TI - The use of micropreparative electrophoresis of protein/peptide isolations for primary structure determinations. AB - High-performance electrophoresis chromatography (HPEC) is a recent development that features continuous-elution gel electrophoresis for isolating proteins or peptides in range of 1 to 300 microgram quantities. Column gel electrophoresis is conducted under thermostated conditions, and the field voltage can be varied within a run with a programmable power supply. Applications of this apparatus in protein purification are presented to demonstrate the utility of the (Model 230A) HPEC. These examples include on-line detection with direct analyte recovery of highly purified sample, which mimics high-performance liquid chromatography, for subsequent structure-function characterization. A method to remove salts from sodium dodecyl sulfate electrophoresed samples for subsequent sequencing or amino acid analysis is described. This desalting procedure recovers from 90%-95% of the sample and employs a low molecular weight cut-off membrane during sample centrifugation onto a polyvinylidene difluoride membrane. Subsequent washings are performed to efficiently remove salts, free amino acids and detergents that are known to interfere with sequence analysis. Sequence information such as initial recovery, repetitive yields and chromatogram comparisons are presented to demonstrate the utility of this procedure when used following isolation of sample with HPEC. PMID- 2257148 TI - Recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) enhances healing and strength of granulation skin wounds. AB - A new animal model to study secondary intention wound healing and the effects of topically applied rhTGF-beta 1 was developed. A time course study was performed of full thickness 6 mm punch wounds placed on the backs of anesthetized pigs and treated once with either 3% methylcellulose or rhTGF-beta 1 in 3% methylcellulose or left untreated. Wounds receiving rhTGF-beta 1 had enhanced tensile strength at days 4 and 7 compared to controls. Studies of the response on days 4 and 7 to graded doses of rhTGF-beta 1 showed that a dose of 250 or 2500 ng rhTGF-beta 1 gave a similar enhanced wound strength, while 25 ng rhTGF-beta 1 had no effect. Blood flow to treated granulating wounds as measured by 141Ce microspheres indicate an increase in flow in wounds treated with 250, 500 or 2500 ng rhTGF beta 1 compared to controls. These results indicate a possible use for rhTGF-beta 1 in enhancing wound healing clinically. PMID- 2257149 TI - Mesoderm induction in Xenopus laevis distinguishes between the various TGF-beta isoforms. AB - Induction of mesoderm in ectodermal explants of Xenopus laevis blastula embryos had previously been shown to respond selectively to TGF-beta 2, with TGF-beta s 1 and 5 having no activity in this assay. As TGF-beta s 1, 2, and 3 are frequently coexpressed in tissues, we wished to examine the activity of TGF-beta 3 relative to that of TGF-beta s 1 and 2 in this assay as well as in other in vitro assays. We report here that when the activity of recombinant TGF-beta 3 is normalized to that of TGF-beta 1 in the assay for growth inhibition in CCL-64 cells, it is also equal to that of TGF-beta 1 in assays for stimulation of both anchorage independent growth of rat NRK cells and chemotaxis of human monocytes. In contrast, in the assay for mesoderm induction, recombinant TGF-beta 3 is 10-fold more active than TGF-beta 2, inducing expression of muscle specific alpha-actin at concentrations as low as 1 ng/ml. These results suggest that more complex systems, in contrast to individual cell types, may respond selectively to the various TGF-beta isoforms and that there might be biological consequences of TGF beta isoform switching in vivo. PMID- 2257150 TI - Basic fibroblast growth factor in ovulatory cycle and postmenopausal human endometrium. AB - Biopsies of human endometrium were studied for the presence of basic fibroblast growth factor (bFGF). An immunoreactive Mr 18,000 bFGF-like molecule was detected at high levels both in ovulatory cycle and postmenopausal endometrium. This molecule was identified as bFGF on the basis of its molecular weight, its affinity for heparin, its capacity to induce plasminogen activator production and cell proliferation in endothelial GM 7373 cells, and its cross-reactivity with various anti-bFGF antibodies. The levels of endometrial bFGF do not change during the menstrual cycle but they increase significantly after menopause, as evaluated both by biological and immunological assays. Lower levels of an acidic FGF-like activity were also evident in ovulatory cycle endometrium but, at variance with bFGF, no significant increase of this activity was observed in postmenopausal endometrium. These data represent the first characterization of a polypeptide growth factor present in human endometrium. PMID- 2257151 TI - Insulin-like growth factor I promotes nerve regeneration: an experimental study on rat sciatic nerve. AB - Insulin-like growth factor I (IGF-I; somatomedin C) has previously been demonstrated, with immunohistochemical methods, to accumulate locally at the site of trauma of an injured peripheral nerve. In the experiments reported here a Y shaped silicone-chamber system was used to test if local infusion of IGF-I had supportive effects on nerve regeneration. The proximal end of a cut sciatic nerve was inserted into one channel of the Y-shaped chamber and the length and growth direction of the regenerating myelinated axons were evaluated after 1 month. When IGF-I (250 micrograms/ml 0.5 microliters/h) was infused into one channel by an osmotic pump, the length of the regenerating axons increased significantly compared to the control groups with no IGF-I added. In some instances the regenerating axons grew towards the osmotic pump. It is concluded that local infusion of IGF-I at appropriate concentration promotes regeneration of a peripheral nerve. It exerts a neuronotrophic but not a clear chemotactic effect. PMID- 2257152 TI - [Oncogene research using Drosophila as a model system]. PMID- 2257153 TI - Selection at the ABO locus in the Japanese population. AB - Hiraizumi et al. (1973b) concluded that maternal-fetal ABO incompatibility effect upon the frequency of prenatal deaths was totally absent in two modern Japanese cities, Ohdate and Akita. However, they found a significant heterogeneity in the frequency of prenatal deaths among 16 mating types and suggested that the viability of A-bearing fetuses was higher than that of others, hence the frequency of prenatal deaths decreased with the increasing probability of producing A-bearing fetuses. Further analyses were performed in the present study and the above suggestion was confirmed. Then, the average numbers of prenatal deaths and pregnancies per couple were analyzed separately for their relationships with the probability of producing an A-bearing fetus. The results were found to be consistent with the model that the average numbers of prenatal losses per couple are approximately the same between two groups of matings, one producing and the other not producing A-bearing fetuses, but such losses occur more frequently for the A-bearing fetuses than others at the very early stage of pregnancy such that wives may not recognize such losses. Although the stages of losses are different between A-bearing and other fetuses, the net losses are nearly the same between them, so that such losses will not be reflected in the segregation frequencies among children, as shown by Hiraizumi et al. (1973a). PMID- 2257154 TI - [Atrial pacing and the exercise test in the evaluation of coronary disease. A comparative study]. AB - OBJECTIVE: to compare the relative value of Atrial Pacing and Exercise Electrocardiography in the diagnosis of Myocardial Ischaemia. DESIGN: prospective study in patients referred for coronary cineangiography. SETTING: Cineangiography and Ergonometry Departments of Cardiology Service. Santa Maria Hospital. PATIENTS: 16 patients (mean age 52.4 +/- 6.3), 13 males and 3 females. All were submitted to Atrial Pacing, Exercise Test and Coronariography. RESULTS: both tests were concordant in all cases but one, with negative Atrial Pacing, positive Exercise Test and negative Coronariography. CONCLUSIONS: Atrial Pacing compares favourably with Exercise Test in the diagnosis of Coronary Ischaemic Disease. It may constitute a valid alternative in patients unable to perform a conclusive Exercise Test. PMID- 2257155 TI - [Surgery for infectious endocarditis]. AB - OBJECTIVE: to assess the experience of both departments in the surgical therapy of infective endocarditis--indications and results. DESIGN: retrospective analysis on clinical data, surgery and follow up. SETTING: patients (pts) studied in the Cardiology Department and Cardiothoracic Surgery Department of the Santa Marta Hospital in Lisbon. PATIENTS AND INTERVENTIONS: sequential sample of 28 patients (11 females, 17 males, mean age 39 years) submitted to surgery between 1978 and 1987 for infective endocarditis. MEASUREMENTS AND RESULTS: the indications for surgery were: heart failure (15 pts), "resistant" infection (8 pts), emboli (4 pts) and "large" vegetations shown by echocardiography (2 pts). Surgical mortality -27.5%. Four patients developed periprosthetic leaks. There was an improvement in functional class of the survivals. CONCLUSION: the indications for surgery were heart failure, "resistant" infection, emboli and "large" vegetations. There was a high surgical mortality, namely in the patients with resistant infection, severe heart failure and periprosthetic leaks. In the follow up there was a net improvement of functional class. The morbidity is due to the periprosthetic leaks, which induced most of the reoperations. PMID- 2257156 TI - [Influence of recipient auricular contraction on the left ventricle filling pattern of the transplanted heart studied with pulsed Doppler echocardiography]. AB - OBJECTIVES: to evaluate the influence of recipient atrial contraction (RAC) timing on left ventricular filling pattern (LVFP), assessed by Pulsed Doppler, in orthotopic transplant recipients (OTR). STUDY DESIGN: prospective study of OTR. SETTING: patients (pts) submitted to orthotopic heart transplantation at Hospital de Santa Marta, from April/87 to March/89, in routine evaluation. PARTICIPANTS: nine pts, aged 21 to 55 years (mean = 32 +/- 11), 0.5 to 20 (mean = 7.4 +/- 6.9) months post-operatively. METHODS: in each pt 40 to 60 (mean 52) consecutive cardiac cycles were analysed; five groups (Gr.) were considered, according to RAC (P wave) position in the cardiac cycle: Gr. I--Early systole, GR. II--late systole, Gr. III--early diastole, Gr. IV--late diastole and Gr. V--absent. The following parameters were studied: peak early diastolic mitral flow velocity (Evel), peak late diastolic mitral flow velocity (Avel), ratio Evel/Avel, (E/A) and pressure half time (PHT). RESULTS: 1) Evel and E/A were significantly higher, Avel lower, and PHT shorter, in Gr II and III; 2) Avel was higher and E/A smaller in Gr. IV; 3) no statistically significant differences were found betwenn Gr. I and V, for any of the parameters analised. CONCLUSIONS: the timing of RAC significantly influences LVFP and it must be considered on Echo-Doppler analysis of diastolic function in OTR. PMID- 2257157 TI - [A case of rupture of the left ventricle free wall with papillary muscle dysfunction following acute myocardial infarction, operated on successfully]. AB - The authors present a case of left ventricular free wall rupture post acute myocardial infarction, associated with mitral papillary posterior muscle necrosis, operated by infartectomy and mitral valvular protesis replacement. They refer the various complications occurred during the hospital staying, and discuss its medical and surgical approach. The patient was discharged alive and six months after the infarction keeps a moderate activity. PMID- 2257158 TI - [Aorto-left ventricular tunnel arising from the left sinus of Valsalva]. AB - Aortic-left ventricular tunnel (ALVT) is a rare congenital anomaly in which an abnormal communication connects the ascending aorta with the left ventricle, bypassing the aortic valve. Usually the ALVT takes its origin from the right aortic sinus. We report a patient with an ALVT arising from the left sinus of Valsalva who underwent surgery at five months of age. The diagnosis was first established by two-dimensional echocardiography. PMID- 2257159 TI - [Transesophageal Doppler echocardiography in the evaluation of cardiac pathology]. AB - Transesophageal echocardiography is one of the most important innovations that have lately turned up for the evaluation of the cardiac patient. This technical approach consists not only of the study of the two dimensional image but of the cardiac flows obtained with pulsed and color Doppler as well, using a gastroscopic probe to which an ultrasonic transducer has been adapted. In this paper we make a revision of the methodology used in our laboratory. We discuss the utility of this technical approach not only for the study of the ambulatory patient but also for the critically ill patient. PMID- 2257160 TI - [Automatic measurement of arterial pressure. A new method for analysis, quantification and evaluation of hypertensive disease]. AB - The authors try to analyse the role of ambulatory 24 h blood pressure monitoring (ABP) in the diagnosis of hypertension, and review medical literature on this subject. They emphasized the quantification and definition value of normal results and circadian profiles in ABP. The accuracy of the device and the choice of a correct statistical parameter of prognosis is essential in all prospectives studies. In the future a better correlation is expected between blood pressure and organ damage when blood pressure is measured by ambulatory recordings then office method. PMID- 2257161 TI - [Value of the ergometric test after myocardial infarction]. AB - Exercise stress testing (EST) after myocardial infarction helps to define the clinical subsets of patients at high and low risk. It should be performed before hospital discharge, unless a contraindication exists. In order to exclude false positives, EST must be repeated 4-6 weeks later. EST helps to recognize the presence of residual ischaemia. Significant ST segment depression during exercise, associated or not with angina, is the most important indicator of ischemia. These patients with ischaemia at distance i.e., those with ST segment changes in ECG leads without W waves, are at high risk. Some continuous exercise variables (degree of ST deviation, time of recovery and exercise duration) are related to cardiac mortality. Exercise induced complex ventricular arrhythmias seem to be related to left main or three vessels disease, and a greater likelihood of sudden death, particularly when coexist a low ejection fraction, important segmentar disturbances of contractility and ST segment depression. EST after myocardial infarction has great value to assess the results of medical therapy and/or coronary angioplasty or bypass grafting. EST also constitutes a valuable clinical tool to support a comprehensive rehabilitation programme. PMID- 2257162 TI - Antigens recognized by the human immune response to vaccination with a bivalent hardjo/pomona leptospiral vaccine. AB - Serum from volunteer subjects vaccinated with a bivalent whole cell vaccine of Leptospira interrogans serovar hardjo/serovar pomona grown in protein-free medium, was tested by the microscopic agglutination test (MAT), enzyme immunoassay (EIA) and immunoblotting. Specific IgM antibodies to either serovars hardjo or pomona were detected in some subjects as early as 6 days after vaccination with peak antibody levels occurring 13-68 days after vaccination. Whereas all subjects produced specific IgM to both serovars, not all produced specific IgG to both serovars. Immunoblotting with hardjo sonicate revealed that all subjects produced IgM antibodies reacting with the 15, 23 and 28 kDa components of hardjo lipopolysaccharide (LPS), and most produced IgM antibodies that reacted with the 34.5 kDa flagellar doublet. In contrast, not all sera immunoblotted against pomona sonicate reacted with the 29 and 35 kDa components of pomona LPS. However all subjects produced antibodies reacting with a diffuse 14.4-27 kDa band. These antibodies appeared early in the immune response. Serum from the one vaccinated subject tested protected hamsters from acute lethal infection with serovar pomona. PMID- 2257163 TI - Detection of Staphylococcus aureus infection by enzyme-linked immunosorbent assay and immunoblotting, using high molecular weight staphylococcal proteins. AB - Two high molecular weight staphylococcal proteins, fibronectin-binding protein and a Mr 200,000 protein, were investigated as antigens for serodiagnosis of staphylococcal infections. Sera from patients with staphylococcal infections and from controls were subjected to immunoblot analysis with staphylococcal lysate proteins to identify staphylococcal antigens to which patients with staphylococcal infections specifically exhibited antibodies. One such protein was found in the Mr 200,000 region. This protein was purified and used as antigen in ELISA and compared with other antigens, namely fibronectin-binding protein(s) (FNBP, Mr 185,000), alpha-toxin and teichoic acid. Sera from patients with staphylococcal infections contained antibodies to the high molecular weight proteins in higher titers than sera from patients with non-staphylococcal infections or healthy subjects. Based on their amino-acid compositions and different abilities to bind fibronectin it was concluded that the Mr 200,000 protein and FNBP were not identical. PMID- 2257164 TI - Induction of tumoricidal activated macrophages by a liposome-encapsulated glycolipid, trehalose 2,3,6'-trimycolate from Gordona aurantiaca. AB - A mycolic acid-containing glycolipid, trehalose 2,3,6'-trimycolate, prepared from a non-pathogenic acid-fast bacterium Gordona aurantiaca, was shown to induce strong tumoricidal activity in peritoneal exudate cells by intravenous or intraperitoneal injection of liposome-encapsulated preparations. The mycolic acid derivative containing a high proportion of unsaturated fatty acids rendered macrophages cytotoxic against syngeneic mastocytoma cells in the absence of endotoxin, for over 14 days after the injection. The macrophages were ascertained to be at low intracellular levels of a lysosomal enzyme beta-galactosidase and an ectoenzyme alkaline phosphodiesterase, a specific pattern as previously described for "primed macrophages". However the culture supernatants of the peritoneal exudate cells were not cytotoxic. PMID- 2257165 TI - Purification and partial characterization of a cohaemolysin (CAMP-factor) produced by Streptococcus canis. AB - A cohaemolysin from the culture supernate of a canine pathogenic group G streptococcus (S. canis) was purified to electrophoretic homogeneity. The purification procedure involved ammonium sulphate precipitation, ultrafiltration, gel filtration and preparative isoelectric focusing. The cohaemolysin consisted of a single polypeptide chain, 18.6 kDa, with an isoelectric point at pH 5.1. The protein reacted with an homologous antiserum, appeared to be trypsin-sensitive and relatively heat-stable. The cohaemolysin did not show any non-specific IgG binding activities. PMID- 2257166 TI - Natural killer activity against human K562 tumour cells during Plasmodium cynomolgi malarial infection of rhesus monkeys. AB - This study assessed the natural killer (NK) cell activity profile during Plasmodium cynomolgi infection in rhesus monkeys. There was a significant decrease in the NK cell activity in the peripheral blood leukocytes of infected monkeys during the early, ascending phase of infection. However, as the parasite load decreased, NK cell activity returned to normal levels. This could be correlated with the peak increase in lymphocyte counts. This indicated that a decrease in NK cell activity observed at an earlier stage during an active P. vivax malarial infection was a temporary phenomenon. PMID- 2257167 TI - Inhibition of Helicobacter pylori haemagglutination activity by human salivary mucins. AB - Thirty isolates of Helicobacter pylori from gastric biopsies agglutinated human erythrocyte suspensions. Crude mucin preparations derived from saliva of 20 different donors were examined for their ability to inhibit haemagglutination. All mucin preparations exhibited strong inhibitory activity. Removal of sialic residues from mucin preparations by treatment with neuraminidase resulted in a substantial reduction of their inhibitory activity. The mucin preparations had no bactericidal or aggregation activity for H. pylori. These results are discussed in the context of the role of mucins in colonization of the gastric mucosa by H. pylori. PMID- 2257169 TI - Gut-associated immune effector responses in immunocompetent and immunocompromised mice with Giardia lamblia. AB - Significantly higher Giardia lamblia trophozoites load in the intestine of infected mice accompanied pronounced influx of suppressor/cytotoxic T cells (Lyt 2.2+), T cells (Thy 1.2+) and significant reduction in IgA-containing cells in the gut during the establishment and peak phases of infection. The induction of helper/inducer T cells (Lyt 1.1+) and significant enhancement of IgA-containing cells in gut resulted in the decline of the trophozoite loads. However, the prior treatment of animals with dexamethasone alone resulted in significant reduction in helper/inducer T cells (Lyt 1.1+) and the IgA-containing cells in the gut; the percents of suppressor/cytotoxic T cells (Lyt 2.2+) and IgM-containing cells remained unaltered. Although the G. lamblia infection in such animals further significantly increased the influx of suppressor/cytotoxic T cells, the late response of helper/inducer T cells and IgA-containing cells was abrogated during the decline phase of infection. The significant reduction in the trophozoite load - despite immuno-suppressive therapy - appeared to be due to unaltered IgM response in such animals which probably took over the function of IgA in defense against G. lamblia. The data of the investigation thus suggested a role of helper/inducer T cells and antibodies producing cells in gut as important effector cells resulting in the termination of primary G. lamblia infection. PMID- 2257168 TI - Seroepidemiology of Helicobacter pylori infection in Greece. AB - Helicobacter pylori infection is strongly associated with chronic gastritis and peptic ulceration. As the prevalence of H. pylori infection in southern European populations is not known, a serological survey of 1069 samples from three different age groups in the Greek population was carried out with an enzyme linked immunosorbent assay (ELISA) for antibodies to these bacteria. The antigen was an ultracentrifuged supernate of whole cell sonicates of 5 isolates of H. pylori assessed by electrophoresis and by immunoblotting with negative and positive sera. The sensitivity of the test was 97.43% and the specificity 100% for IgG antibodies; IgA and IgM antibodies to the antigen preparation were not found. Antibodies to H. pylori were detected among 39.4% of children aged 1-10 years, 67.1% of recruits (20-27 years) and 70% of blood donors (20-50 years). The prevalence of antibodies did not differ with sex in each of the age groups. The proportion of individuals with antibodies to H. pylori was higher in the younger age groups than those reported for similar age groups in western Europe. PMID- 2257171 TI - Use of live Saccharomyces cerevisiae cells as a biological response modifier in experimental infections. AB - A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae. S. pneumoniae and S. pyogenes A produced by intranasal inoculation. Yeast pre-treatment also increased the efficacy of antibiotic therapy in bacterial infections and of antiviral drugs in viral infections. Yeast treatment of animals stimulated phagocytosis, activated the complement system and induced interferon which are likely to represent the main mechanisms of action whereby pretreatment of mice with live S. cerevisiae cells increases resistance to infection. It is concluded that preventive administration of live Saccharomyces cerevisiae cells should be used for increasing resistance to bacterial infections, in particular of the respiratory tract, or to viral infections, as well as an adjunct to antibiotic and antiviral drug therapy. PMID- 2257170 TI - Structures involved in the binding of human fibrinogen to Candida albicans germ tubes. AB - Recent evidence for the interaction between human fibrinogen and Candida albicans germ tubes have led us to attempt to characterize the structures involved. Using 125I-radiolabeled proteins, fibrinogen purified by affinity chromatography and its plasmin degradation products, the binding sites on the fibrinogen molecule appeared to be located specifically in the D-domain. Conversely to the fibrinogen and the fragment D, radiolabeled fragment E, however, did not interact with cells. The binding was time-dependent, saturable and reversible. Scatchard analysis of the data obtained revealed an average of 6000 binding sites per germ tube with dissociation constant (Kd) of 5.2 X 10(-8) M. No potent competition was observed for a range of different proteins and carbohydrates. Fibrinogen fragment D binding proteins were identified using a dithiothreitol-iodoacetamide extract of the fungus. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, one component of 68 kDa was detected. Thus, the presence of fibrinogen binding proteins specifically localized on the cell wall surface of C. albicans germ tubes may constitute one of the factors involved in the development of candidosis. PMID- 2257172 TI - Recognition of 29 kDa surface-associated adhesive molecule of Entamoeba histolytica by monoclonal antibodies. AB - Monoclonal antibodies have been developed and used as specific probe to locate and identify a 29-kDa molecule of axenic Entamoeba histolytica trophozoites. Monoclonal antibody produced by clone C8 (MoAb C8) strongly agglutinated the amoebic trophozoites. The immunofluorescence of live E. histolytica trophozoites and surface fluorescence of acetone-fixed trophozoites by MoAb C8 indicated existence of a 29-kDa molecule on surface-associated plasma membrane of E. histolytica. The monoclonal antibody belonged to IgG1 isotype. The prior treatment of E. histolytica trophozoites with MoAb C8 resulted in significant (P less than 0.01) reduction in adherence of amoebic trophozoites to cultured Chinese Hamster Ovary cells and significant (P less than 0.01) reduction in cytotoxicity to cultured Baby Hamster Kidney cells. Pretreatment of amoebic trophozoites with MoAb C8 prior to cultivation in TPS-1 medium resulted in significant (P less than 0.01) reduction in growth of the parasite. Thus, the data suggested that the surface-exposed 29-kDa molecule may be one of the receptors involved in E. histolytica host cell interactions and may possibly modulate amoebic disease processes. PMID- 2257173 TI - Suppressive effect of lipid A partial structures on lipopolysaccharide or lipid A induced release of interleukin 1 by human monocytes. AB - Experiments were designed to investigate the significance of lipid A partial structures, precursor Ia (compound 406), and lipid X (compound 401) to serve as antagonists of interleukin 1 (IL-1) release from human mononuclear cells and monocytes induced by lipopolysaccharide (LPS, endotoxin) of Salmonella abortus equi or synthetic Escherichia coli lipid A (compound 506). A definite inhibition mediated by lipid A partial structures on IL-1 release induced by LPS or lipid A was found in repeated experiments. The inhibitory effect was exerted not only on IL-1 release, but also on IL-1 peptide synthesis at the intracellular level. The results also show that lipid A partial structures have suppressive effects even when added 1-4 h after LPS or lipid A. We conclude from these results that lipid A partial structures (precursor Ia and lipid X) have potent immunomodulatory effects on LPS- and lipid A-induced IL-1 release and may become useful reagents to study the mechanism of interaction of LPS and lipid A with cells of the immune system. PMID- 2257174 TI - Ethics and the new genetics. AB - Recent developments in recombinant DNA technology have resulted in a rapidly expanding range of new diagnostic and therapeutic opportunities for families with inherited disorders. They are also beginning to impinge on society as a whole as progressively more is learned about the human genome, as the community becomes more aware of the role of genes in disease, and as we start to consider the implications of being able to define individual susceptibility to both monogenic and multifactorial disorders. As we implement the new technologies, careful consideration must be given to the ethical issues which arise so that maximum benefit can be obtained by individuals and the wider community. PMID- 2257175 TI - Surgical aspects of primary vesico-ureteric reflux. PMID- 2257176 TI - The management of cerebral palsy. PMID- 2257177 TI - Vaccine prevention of Haemophilus influenzae type b disease. PMID- 2257179 TI - Cell therapy: a cruel and dangerous deception. A drama in three acts. AB - 'Cell therapy' is a long-standing quack remedy used in Germany and adjacent countries. Organ extracts from fetal or young animals, fresh or lyophilized, are injected, with the intention of achieving 'cure' or at least 'treatment' of postulated organ deficiencies or failures. In Germany and in Australia 'cell therapy' has been administered in Down syndrome, cancer and for traumatic and other brain injuries. The preparation is banned in Germany, and can be lawfully imported into Australia only with express Ministerial permission. Even so its illicit use has been widespread. Morbidity and mortality have been reported since 1956, mostly in the German literature. There is a finite risk of infection with slow viruses of animal origin. This possibility should be considered in otherwise unexplained spongiform encephalopathy or leuco-encephalitis. Legal problems are considerable when quack practitioners (medically qualified or otherwise) administer such a preparation to children or legally incompetent adults. PMID- 2257178 TI - The changing growth of aboriginal children. AB - We have used data from children at an Aboriginal settlement in Queensland to demonstrate the changing patterns of growth over the last 30 years. In cohorts of children born during the early 1950s and 1960s the mean weight-for-age value was satisfactory for the first three months of life, but then fell until aged 12 months and remained at about 92% of the NCHS median value until 5 years old. In the cohort born in 1972-73 there was some improvement and in the 1982-83 cohort the mean weight-for-age value was close to international levels from 1 to 5 years. The decline in weight-for-age between 3 and 12 months was still present. Length-for-age values were not available in the 1950s and 1960s but the mean value increased from the 1972-73 cohort to the 1982-83 cohort, which was close to international levels. The mean weight-for-length was close to international levels in the 1972-73 cohort, but in the 1982-83 cohort was high from 3 to 12 months and then fell close to the international level. These data indicate that the children at this Aboriginal settlement are now growing satisfactorily. The impaired growth between 3 and 12 months needs further investigation, but most of the earlier concerns about poor growth appear to have been resolved. PMID- 2257180 TI - Validation of an asthma knowledge questionnaire. AB - Asthma is responsible for much morbidity and mortality, which might be decreased by increasing parental and patient knowledge about asthma. This report describes the development and validation of an asthma knowledge questionnaire for use in the assessment of asthma knowledge. Two groups of respondents were examined. One group was designated 'high knowledge' and the other 'low knowledge'. The questionnaire had a maximum possible score of 31. The mean score of 69 'high' knowledge parents was 25.3 (median 25, range 18-31). By contrast, the mean score of 69 'low' knowledge parents was 13.0 (median 13, range 0-21). The difference between the two groups was statistically significant (P less than 0.0001). The questionnaire results were reproducible (tau = 0.94, P less than 0.01). Demographic characteristics such as education and socio-economic status were not important confounding variables. Face and content validity of the questionnaire were based on reference to published experience. Concurrent validity was demonstrated by the ability of the questionnaire to distinguish low from high knowledge parents. The questionnaire should prove to be a valuable research tool for the assessment of asthma knowledge either as part of an educational intervention or in a clinical situation. PMID- 2257181 TI - A 12-year experience of retinopathy of prematurity in infants less than or equal to 28 weeks gestation or less than or equal to 1000 g birthweight. AB - This study reported the prevalence and severity of retinopathy of prematurity (ROP) in less than or equal to 28 weeks gestation or less than or equal to 1000 g birthweight infants over a 12-year period. Among 328 survivors of less than or equal to 28 weeks gestation, 30% had ROP, 12% had severe ROP of Stage 3 or worse, 5% had at least one blind eye and 3% were bilaterally blind. Among 201 survivors of less than or equal to 1000 g birthweight, the above abnormalities were found in 40, 16, 6 and 4% respectively. In both cohorts there was a significant increase in the prevalence of ROP and severe ROP between the period 1977-80 and 1981-84, but the lesser increase observed between the periods 1981-84 and 1985-88 was not statistically significant. The rates of ROP-induced blindness were not significantly different between the three 4-year periods. An inverse relationship was noted between the prevalence of ROP and gestational age. The results suggest a resurgence of ROP in less than or equal to 28 weeks or less than or equal to 1000 g infants, the cause of which is uncertain. In view of this trend, continued surveillance of ROP is warranted. PMID- 2257182 TI - The chest radiograph in acute bronchiolitis. AB - The relationship between clinical severity, as judged by a clinical scoring method, and the degree of radiological change on a chest X-ray, was assessed in 153 children with acute bronchiolitis. There was no statistical correlation between clinical severity and the degree of radiological change. The majority of radiographs were requested on the assumption that it was a useful routine investigation. We suggest that the request for a chest X-ray in acute bronchiolitis should be made only when the need for intensive care is being considered, where there has been an unexpected deterioration in the child's condition or the child has an underlying cardiac or pulmonary disorder. PMID- 2257183 TI - Neonatal gram negative meningitis: a 10-year review, with reference to outcome and relapse of infection. AB - Twenty-four infants treated for neonatal Gram negative bacillary meningitis over a 10-year period were reviewed to determine the mortality and incidence of complications including relapse. Nine (37.5%) infants died; two survivors had major and 13 minimal or no handicap. Five (21%) infants had a relapse of meningitis after the initial course of treatment; two of these infants had been treated with cefotaxime. The outcome did not correlate with age, sex, gestation, cerebrospinal fluid (CSF) parameters or peripheral neutrophil counts. A poor outcome was associated with thrombocytopenia, persistence of viable organisms in the CSF for more than 24 h and with seizures, particularly in infants aged 7 days or less. There were no clinical or laboratory parameters predictive of subsequent relapse and there was no apparent relationship with choice or dose of antibiotic used or duration of treatment. PMID- 2257184 TI - A system to capture physical examination data suitable for paediatric practice. AB - A method is described to capture data on the physical examination of children. A personal computer with a keyboard, keypad and screen is used along with a menu driven software package. Little knowledge of computing is necessary and the system can be used to produce hard copy when a suitable printer is added. Accumulated data may be transferred to a statistical package for future analysis. The method used to capture data from children with respiratory disease, particularly acute asthma, is described here, but it is stressed that the method can be adapted easily to data collection from the results of the physical examination of any system. PMID- 2257185 TI - Oxandrolone increases final height in Turner syndrome. AB - In order to examine whether the anabolic steroid oxandrolone has any long-term effect on height in Turner syndrome, the short- and long-term effects were studied in a group of 35 individuals with the syndrome. At commencement of treatment, age range was 8.2-16 years (mean 12.9); oxandrolone dosage was 0.07 0.26 mg/kg per day (mean 0.14 mg/kg per day) and continued for 12 months-6 years (mean 33 months), ending at 12-18.5 years (mean 15.6 years). Height velocity increased significantly on therapy from 3.3 +/- 0.1 to 5.8 +/- 0.3 cm/year at 6 and 12 months, and maintained at 4.8 +/- 0.3 cm/year by two years (all P less than 0.001). Girls who were younger and whose bone age was delayed grew faster (P less than 0.001). Oxandrolone dose correlated with height velocity at 12 (r = 0.39, P less than 0.05) and 18 months (r = 0.31, P less than 0.05). Both height standard deviation score (SDS) and estimated mature height (EMH) increased significantly by the end of treatment (-0.31 +/- 0.2 to 0.45 +/- 0.2, and 140.4 +/- 1.1 cm to 144.4 +/- 1.1 cm respectively (both P less than 0.0001). In 23 patients who had completed growth at a mean age of 20.6 +/- 0.83 years, final height was 145.5 +/- 1.3 cm. This was not significantly different from EMH of 144.9 +/- 1.3 cm at the end of therapy, and based on a pre-treatment EMH of 140.5 +/- 1.3 cm, represented a mean height gain of 5 cm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257187 TI - Inappropriate use of contrast studies. PMID- 2257186 TI - Hyperglycaemia complicating haemolytic uraemic syndrome. AB - The occurrence of hyperglycaemia and insulin deficiency in a young child receiving peritoneal dialysis during the course of haemolytic uraemic syndrome (HUS) is described. This unusual complication may have been due to microvascular disease involving the pancreas. Plasma glucose should be monitored during HUS, particularly if dialysis with fluids containing high dextrose concentrations is required. PMID- 2257188 TI - The myth of the 'test feed'. PMID- 2257189 TI - [Esophageal motility disorders in cirrhotics treated by sclerosing the varices]. AB - We performed esophageal manometry on 17 cirrhotic patients (group I) treated with repeated varicose sclerosis (VS) after the varices had been completely eradicated. We used 5% ethanolamine oleate with the free hand technique, administering intra-varix injections at the cardia level, never exceeding 25 cc per session. The first two sessions were spaced a week apart, and the consecutive ones were on a monthly basis. The mean number of VS sessions was 5.52. The esophageal motility study was carried out on the average 12.3 months after the last VS session, with a minimum of six and maximum of 17 months. As controls we used 16 cirrhotic patients with unsclerosed varices (group II) and 26 healthy subjects (group III). The mean age and patient distribution were similar, according to Pugh grading. The length of the lower esophageal sphincter (LES) and the amplitude of the propulsive waves in the middle esophagus were similar in all three groups. We found the LES pressure to be significantly reduced in group I (17.52 +/- 2.8 mmHg) in relation to group II (20.26 +/- 2.49 mmHg) (p less than 0.001) and group III (22.86 +/- 3.73 mmHg) (p less than 0.01). The group II patients showed significantly lower pressure levels than the group III ones (p less than 0.05). The amplitude of peristaltic waves in the distal esophagus was significantly less in group I (22.94 +/- 7.31 mmHg) than in group II (37.46 +/- 10.95 mmHg) (p less than 0.01) and group III (44.8 +/- 11 mmHg) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257190 TI - [Compensatory reaction of the ascending colon following jejuno-ileal bypass. Experimental study]. AB - The series of physiopathologic consequences and the adaptive response that appears in the residual intestine following intestinal by-pass surgery has been widely studied. The same is not true for the ascending colon. Having demonstrated the adaptive changes this organ undergoes after a massive enterectomy, we carried out the present study to evaluate the compensatory reaction after an intestinal by-pass. A total of 115 Wistar rats weighing 350-550 g were used. Twenty animals made up group 0 (control), 30 underwent intestinal section (group II) and 65 received a jejuno-ileal by-pass (group III), with latero-lateral anastomosis. After weight control was performed the animals were sacrificed at 15, 30, 45 and 60 days, and samples were taken from the ascending colon for optical microscopy (OM), scanning electronic microscopy (SEM) and transmission electronic microscopy (TEM). All objective data were quantified and statistical studies carried out. The by-pass animals showed statistically significant ponderal drops (p less than 0.001), an expression of the malabsorption disorder the by-pass produced. Groups 0 (control) and I (IS) showed no macroscopic, microscopic or ultrastructural changes. The by-pass animals, however, manifested colic dilatation with a significant increase in thickness, to the detriment of the muscularis and mucosa, and greater crypt depth with a relative decrease in the number of goblet cells. Enterocytes increased in number and size. These changes were statistically significant in relation to groups 0 and I. The above findings were confirmed ultrastructurally. In the scanning electronic microscopy after 30 days, the colic mucosa had an irregular appearance, with elevations but no foliated appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257191 TI - [Arteriovenous fistula of the cecum diagnosed by digital angiography]. AB - We report the case of a 69 year-old female, with cardiac disease, hypertension, and chronic renal failure treated by hemodialysis; she had several episodes of gastrointestinal hemorrhage, which could not be diagnosed by conventional methods. Digital angiographic study demonstrated the exact cause: it allowed to localize an arterio-venous malformation. A right hemicolectomy was performed and the pathologic study showed the presence of an arteriovenous fistula. Three years later the patient is free of symptoms. We recommend digital angiography in cases of gastrointestinal hemorrhage of unknown or unclear etiology, particularly in patients in chronic renal failure, on the basis of the association of hemodialysis and arteriovenous malformation. PMID- 2257192 TI - [Subcutaneous emphysema as the initial manifestation of perforation of a hollow abdominal viscus]. AB - The authors reports a case of cervical and abdominal subcutaneous emphysema, associated to pneumoretroperitoneum and pneumomediastinum, with no free air in the abdominal cavity, secondary to perforated diverticulitis of the sigmoid colon. We comment the rarity of this clinical presentation, the physiopathologic mechanisms of subcutaneous air presence in cases of non instrumental perforation of abdominal viscera and the ominous significance of the subcutaneous emphysema in such perforations. PMID- 2257193 TI - [Acute, non-lithiasic, amebic cholecystitis]. AB - The estimated percentage of non calculous cholecystitis is 2-14%. In most cases it is difficult to identify the cause and in very few cases it is possible to establish the etiology. Few cases are secondary to bacterial infections and the cause is very rarely a parasitic infection. We present a case of acute cholecystitis secondary to Entamoeba histolytica infection; the frequency, etiopathogenic mechanism and treatment are discussed. PMID- 2257195 TI - [Extraperitoneal rectal bursting of traumatic origin]. PMID- 2257194 TI - [Tuberculosis of the biliary system: presentation of a case and review of the literature]. AB - We present the case of a female patient with tuberculosis of the gallbladder, the adipose tissue and lymph nodes surrounding the common bile duct; the patient presented with obstructive jaundice. We discuss the diagnostic criteria, approach to the biliary tract and treatment of this type of patients. PMID- 2257196 TI - [Giant lipoma of the cecum as a cause of invagination]. PMID- 2257197 TI - [Giant appendiceal mucocele]. PMID- 2257198 TI - [Effect of cimetidine on free fatty acid liberation]. AB - Certain studies have brought to light the relationship between the administration of cimetidine and alterations of the lipidic metabolism. The changes in cholesterol levels observed after cimetidine administration have not yet been satisfactorily explained, at least in certain aspects. This paper studies free fatty acid behavior in a group of healthy volunteers who were given a 600 mg infusion of cimetidine. A significant drop (p less than 0.05) in fatty acids was found in these subjects in comparison with isolated physiological saline solution infusion. Our results imply that this fatty acid process may be involved in the lipid metabolism changes brought on by cimetidine administration. PMID- 2257199 TI - [Effect of verapamil, a calcium antagonist, on the gastric secretion stimulated by histamine or sham-feeding]. AB - While "in vitro" studies suggest that cholinergic but not histamine stimulation of the parietal cell is closely related to the flow of extracellular Ca++ into the cell, human studies show a great deal of discrepancy. We evaluated the effects of verapamil, a Ca++ channel antagonist, on gastric secretion stimulated by histamine and sham feeding in 19 patients with duodenal ulcers. Verapamil (200 mcg/kg/h in continuous perfusion) had no effect either on acid production or the volume of secretion in 10 duodenal ulcer patients during simultaneous perfusion of three progressive doses of histamine. However, it significantly inhibited both SAO (51.83%; p less than 0.01) and the volume of secretion in the sham feeding period (28.39%; p less than 600.05), in a group of nine duodenal ulcer patients. These findings suggest that the Ca++ acts as an intracellular mediator in the stimulation/secretion relationship for cholinergic but not histaminergic stimulation in humans. PMID- 2257200 TI - Cerebral ischemia in gerbils: postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline. AB - Adenosine agonists have now been shown by several laboratories to have profound neuroprotective effects when administered either pre- or postischemia. In an effort to determine whether these effects are centrally mediated, the effects of the non-brain-permeable adenosine receptor antagonist 8-sulfophenyl-theophylline (8-SPTH) on cyclohexyladenosine (CHA) -mediated protection was determined. Both survival and neurologic outcome were assessed in gerbils following 30 minutes of bilateral carotid occlusion. A dose of 2 mg/kg of CHA 5 minutes postreperfusion resulted in highly significant increases in survival relative to saline injected controls. Administration of doses of 8-SPTH sufficient to normalize the hypotension observed with CHA resulted in the same degree of postischemic protection. Similar results were obtained when neurologic status was evaluated. The results indicate that the neuroprotective effects of CHA are apparently centrally mediated. PMID- 2257201 TI - Identifying priorities of psychosocial need in cancer patients. AB - Inconsistent findings on the efficacy of psychosocial interventions in cancer may be due to their lack of specificity. The aim of this study was to identify priorities of psychosocial need among cancer patients currently receiving treatment in Western Sydney (NSW) as a prelude to targeted intervention. A sample of 188 patients (129 female, median age 52 years, median time since diagnosis 12 months), with various solid tumours, completed a self-report ranking questionnaire listing eight major areas of psychosocial need based on a literature search of relevant studies. The resulting ranking of priorities was: family (1), dealing with emotional stress (2), getting information (3), money (4), work (5), social life (6), sex life (7), and dealing with hospital staff (8). These priorities were independent of demographic characteristics, including time since diagnosis, suggesting that support in the areas of major need may be just as important during follow-up as it is at diagnosis. Males reported less distress than females, and patients with cancer of the head/neck or breast reported most distress. To be maximally effective, psychosocial intervention for cancer patients should focus on the principal areas of family interaction, effective stress management, and access to information. PMID- 2257202 TI - An evaluation of DUPAN-2 in pancreatic cancer and gastrointestinal disease. PMID- 2257203 TI - Dacarbazine (DTIC) and human recombinant interferon alpha 2a (Roferon) in the treatment of disseminated malignant melanoma. PMID- 2257204 TI - Childhood cancer and overhead powerlines: a case-control study. AB - A case-control study has been carried out to examine the occurrence of childhood cancer in relation to the proximity of overhead power lines to a child's home address at birth and to the calculated magnetic field at the address. The study included 374 cases diagnosed in the Yorkshire Health Region between 1970 and 1979, together with 588 matched controls. Magnetic-field strengths at the birth addresses due to the load currents of overhead power lines were calculated on the basis of line-network maps and load records. The results indicate no association between the occurrence of childhood malignancies and either the proximity or the magnetic fields of overhead lines, although the statistical power of the study was limited by the small numbers of children living close to overhead power lines. PMID- 2257205 TI - A randomised study comparing intermittent to continuous administration of magnesium aspartate hydrochloride in cisplatin-induced hypomagnesaemia. PMID- 2257206 TI - Quality of life following a false positive mammogram. AB - To assess how women regard having had a false positive mammogram screening exam, and the influence that this had on their quality of life, 126 such women were interviewed. Their responses were compared to those of 152 women randomly selected among screenees with a negative exam. Eighteen months after the screening the reported prevalence of anxiety about breast cancer was 29% among women with a false positive and 13% among women with a negative screening mammogram (P = 0.001). Of 30 women biopsied, 8 (27%) had pain in the breast and 10 (33%) had reduced sexual sensitivity. A false positive mammogram was described by 7 (5%) of the women as the worst thing they ever had experienced. However, most women with a false positive result regarded this experience, in retrospect, as but one of many minor stressful experiences creating a temporary decrease in quality of life. They report the same quality of life today as women with negative screening results and 98% would attend another screening. Even so, false positive results are a matter of concern, and efforts should be made to minimise this cost whenever a screening programme is conducted. PMID- 2257207 TI - Phase II trial of UFT in advanced colorectal and gastric cancer. AB - A phase II trial of continuous oral therapy with UFT, a combination of uracil and the 5-fluorouracil analogue 1-(2-tetrahydrofuryl)-5-fluorouracil (Futraful, Ftorafur), was conducted in 40 patients with advanced colorectal cancer and 18 patients with advanced gastric cancer. Six partial responses were seen in the 36 evaluable patients with colorectal cancer (response rate 16.6%; 95% confidence limits 6.4-32.8%), and one partial response was seen in the 16 evaluable patients with gastric cancer (response rate 6%; 95% confidence limits 0.27-30.2%). The overall toxicity of the treatment was low, and all patients were treated as outpatients. The results suggest that oral UFT has comparable activity to standard regimes of 5-fluorouracil, and because of the convenience of oral administration is a useful therapy in the management of patients with advanced colorectal cancer. PMID- 2257208 TI - Comparative values of several tumour markers: example of untreated breast carcinoma. PMID- 2257209 TI - Measuring psychological and physical distress in cancer patients: structure and application of the Rotterdam Symptom Checklist. AB - Use of the Rotterdam Symptom Checklist (RSCL) to measure psychological and physical distress as experienced by cancer patients, is discussed in this paper. The stability of the structure of the RSCL was assessed in principal component analyses in three studies: one concerning cancer patients during either chemotherapy or follow-up (n = 86), one done in patients undergoing chemotherapy for advanced ovarian cancer (n = 56), and the third dealing with cancer patients under treatment, disease-free 'patients', and 'normal' controls (n = 611). The psychological dimension proved to be stable across populations. A scale based on this factor was highly reliable (Cronbach's alpha 0.88-0.94). The physical distress is reflected by several dimensions in a homogeneous population (pain, fatigue, gastrointestinal complaints) and undimensionally in a heterogeneous population. Reliability of the physical distress scales is good (0.71-0.88). The current components of the RSCL and the use of individual and disease specific symptoms are discussed. PMID- 2257210 TI - Models for skin tumour risks in workers exposed to mineral oils. AB - The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on the scrotum and the 2.4th power for tumours on the hand and forearms. These results accord well with experiments on animals. There was some evidence of an increasing trend in risk with increasing age at first exposure. PMID- 2257211 TI - Paradoxical effects of 5-FU/folinic acid on lymphokine-activated killer (LAK) cell induction in patients with colorectal cancer. AB - The effects of treatment with 5-FU/folinic acid on interleukin-2 related lymphocyte responses was investigated in 21 patients with advanced colorectal cancer. The treatment was not suppressive of IL-2 related lymphocyte responses. Furthermore, at certain time points in the treatment cycles the capacity to generate lymphokine-activated killer (LAK) cells from the peripheral blood mononuclear cells of these patients was significantly augmented above that observed prior to treatment. These results provide a logical basis for the design of regimens which combine two approaches, each of low individual therapeutic efficacy, to treat patients with advanced colorectal cancer in the hope of increasing clinical response rates. PMID- 2257213 TI - From receipt to publication. PMID- 2257212 TI - Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx. AB - A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique. We found 13 tumours presenting total HLA-ABC loss, five with selective loss of HLA-A antigens and one with absence of HLA-B antigens. These losses were statistically associated with clinical and pathological parameters, such as T stage, degree of differentiation, scores according to the Jakobsson and Glanz grading systems and degree of leukocytic infiltration. Our results lead us to the following conclusions: (a) HLA class I losses were found in a group of tumours showing greater aggressiveness and worse prognosis; (b) these alterations in expression were not associated with an increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to greater local aggressiveness, and the loss of class I antigens seems to constitute an adaptive tumour mechanism to avoid the different anatomical and immunological barriers within the larynx. PMID- 2257215 TI - National cancer control and cancer registration. PMID- 2257214 TI - The feasibility of testing experimentally the dietary fat-breast cancer hypothesis. PMID- 2257216 TI - Treatment strategies. PMID- 2257217 TI - Effect of vascular marker Hoechst 33342 on tumour perfusion and cardiovascular function in the mouse. AB - The fluorescent stain Hoechst 33342 (H33342) has been employed extensively as an in vivo marker of functional tumour vasculature. We have found that H33342 causes a transient, dose-dependent decrease in tumour red blood cell (RBC) flow in SCCVII tumours as measured using laser Doppler flowmetry. After intravenous bolus injection of 15 mg kg-1 to anaesthetised mice, blood flow in subcutaneous back tumours declined to 19 +/- 11% of pretreatment values, returning to normal in less than 7 min. The effect was less pronounced in mice bearing foot tumours in which flow decreased to 52 +/- 14% of pretreatment values in unanaesthetised mice and to 50 +/- 15% in anaesthetised animals. RBC flow in foot tumours remained significantly depressed for only 2-3 min. A dose of 5 mg kg-1 was not significantly vasoactive in back tumours. H33342 also caused a transient 20 +/- 6 mmHg decline in mouse arterial blood pressure. Blood pH and haematocrit, and tumour cell oxygen consumption were unchanged by H33342. H33342-induced flow changes did not affect results obtained using an in vivo double staining protocol provided that the interval between stain injections was greater than 5 min. Due to its transient effects on tumour perfusion, the stain caused radiobiological tumour hypoxia if injected immediately prior to X-irradiation. Injection 20 min before irradiation had no influence on tumour radiation response. We conclude that the transient nature of H33342-induced perturbations in mouse cardiovascular physiology and tumour blood flow must always be considered but do not preclude the use of the stain as a vascular marker to detect spontaneous tumour blood flow fluctuations or acute hypoxia. PMID- 2257218 TI - Disposition of the prodrug 4-(bis (2-chloroethyl) amino) benzoyl-L-glutamic acid and its active parent drug in mice. AB - A novel therapy for improving selectivity in cancer chemotherapy aims to modify distribution of a cytotoxic drug by generating it selectively at tumour sites. In this approach an antibody-enzyme conjugate is allowed to localise at the tumour sites before injecting a prodrug which is converted to an active drug specifically by the targeted enzyme in the conjugate. We present here pharmacokinetic studies on the prodrug 4-(bis (2-chloroethyl) amino) benzoyl-L glutamic acid and its activated derivative, benzoic acid mustard. The glutamic acid is cleaved from the prodrug to form the active drug by carboxypeptidase G2 (CPG2), an enzyme from Pseudomonas sp., which is not found in mammalian cells. The prodrug and its parent active drug were rapidly distributed in plasma and tissues after administration of prodrug or active drug (41 mumol kg-1 intraperitoneally) to mice bearing human choriocarcinoma xenografts. Prodrug and active drug both followed a two-compartment kinetic model. Prodrug was eliminated more rapidly (t1/2 alpha = 0.12 h, t1/2 beta = 0.70 h) than active drug (t1/2 alpha = 0.37 h, t1/2 beta = 1.61 h). Conversion of the prodrug to the activated parent drug was detected within 5 min of administration to mice which had previously received a F(ab')2-anti-human chorionic gonadotrophin antibody (W14A) conjugated to the enzyme, CPG2 (1,000 U kg-1). Tumour was the only tissue that activated all the prodrug reaching the site. It contained the highest concentration of targeted enzyme conjugate capable of catalysing the reaction of prodrug to drug. Plasma and other tissues were also capable of activating the prodrug but active drug production was limited by the amount of enzyme present. The active drug measured in plasma and tissues other than tumour was attributable to residual antibody-enzyme conjugate at non-tumour sites. Low levels of conjugate in tissues and plasma militate against the advantage of tumour localised enzyme therefore necessitating removal of non-localised enzyme. PMID- 2257220 TI - A chelating derivative of alpha-melanocyte stimulating hormone as a potential imaging agent for malignant melanoma. AB - A chelating derivative of alpha-melanocyte stimulating hormone (MSH) has been synthesised, in which two molecules of the hormone are cross-linked by diethylenetriamine pentaacetic acid (DTPA). This compound, bisMSH-DTPA, was equipotent with MSH in an in vitro tyrosinase assay with Cloudman S91 melanoma cells. When DBA/2 mice bearing the same tumour were injected with bisMSH-DTPA labelled with the gamma-emitting isotope indium-111 (111In), the radioactivity became rapidly associated with the melanoma tissue. By 24 h post-injection, radioactivity in tumour tissue was significantly higher (P less than 0.001) than in spleen, lung, brain, eye and skin. Uptake of radioactivity by the tumours was inhibited by a 200-fold molar excess of MSH, whereas uptake by liver, kidney, spleen, lung, brain, eye and skin was unaffected. We conclude that bisMSH-DTPA may offer an alternative to antibody targeting in the imaging of malignant melanoma. PMID- 2257221 TI - Spontaneous production of interleukin 6 by adult T-cell leukaemia cells. PMID- 2257219 TI - Distribution of pimonidazole and RSU 1069 in tumour and normal tissues. AB - The tritium-labelled analogues of pimonidazole and RSU 1069 were injected into mice bearing the KHT murine sarcoma which has a hypoxic cell fraction of approximately 10%. The distribution of activity at 24 h was recorded using autoradiography and measurement of tissue activity. Autoradiographs with both drugs showed high activity in particular cells within tumour, eye (melanin associated cells), eyelid (Meibomian gland), liver (centrilobular area), skin (sebaceous gland and melanin), stomach (squamous area), footpad, oesophagus, labial gland, Zymbal's gland, preputial gland, parotid gland (intralobular ducts) and airway epithelium. These tissues had previously been identified as sites of binding of misonidazole. The measurement of total tissue radioactivity showed significantly higher activity in liver, eyelid (Meibomian gland), oesophageal lining, kidney and labial gland than was found in the tumour. PMID- 2257222 TI - Necrosis in non-tumour tissues caused by flavone acetic acid and 5,6-dimethyl xanthenone acetic acid. PMID- 2257223 TI - Growth and radiosensitivity testing of human tumour cells using the adhesive tumour cell culture system. AB - The radiosensitivity of human tumour cell lines and cells cultured from xenografts or biopsy specimens was measured using the adhesive tumour cell culture system (ATCCS). For cell lines the derived surviving fractions at 2 Gy were in good agreement with values obtained by clonogenic assay. However, the assay tended to overestimate survival at higher radiation doses, and thus to give a false impression of radioresistance. When cells taken from xenografts or tumour biopsies were cultured there was no evidence for selective growth of tumour cells: fibroblast-like cells commonly grew. Immunohistochemical staining against the intermediate filament, vimentin, supported the mesenchymal origin of the fibroblast-like cells. In cultures of artificial mixtures of tumour cells and fibroblasts, low proportions of fibroblasts were not excluded by the assay and consequently modified the radiation response. The majority of cultures grown from bladder carcinoma biopsy specimens appeared fibroblast-like, although in some cases clearly distinguishable colonies of tumour cells were also grown. In such tumour types the reliable measurement of radiosensitivity in cells taken from biopsies will require further development of techniques that allow the selective growth of tumour cells. PMID- 2257224 TI - Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. AB - We investigated the effect of the flavonoid quercetin (Q) on the proliferation of the ovarian cancer cell line OVCA 433. Growth experiments demonstrated that Q exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth. Cell cycle analysis showed that the growth inhibitory effect of Q was due to a blocking effect in the GO/G1 phase. Using a whole cell assay with (6.7-3H) oestradiol (3H-E2) as tracer we demonstrated that OVCA 433 cells contain type II oestrogen binding sites (type II EBS). Competition analysis showed that Q competed for 3H-E2 binding to type II EBS while both rutin and hesperidin did not. Appreciable amounts of type II EBS were also detected in seven primary ovarian tumours. Our results suggest that Q may regulate ovarian cancer cell growth through a mechanism involving a binding interaction with type II EBS. This mechanism could also be active in vivo since primary ovarian tumours contain type II EBS. PMID- 2257225 TI - Cisplatin and CCNU synergism in spheroid cell subpopulations. AB - The cytotoxicity of two antineoplastic drugs, cisplatin and CCNU, was evaluated in Chinese hamster V79 multicell spheroids using the drugs as single agents or combinations. Cells obtained from different depths within spheroids 550-750 microns in diameter showed different sensitivities to the two agents; the external cells of the spheroids were more sensitive than the internal cells to cisplatin, whereas the internal cells were most effectively killed by CCNU. Combining the two agents produced the expected 'complementary' activity, and in addition, synergism was observed between the drugs at exposure levels practical for clinical use. For the combination treatments, both the net pattern of cell killing through the spheroid and the degree of interaction between the agents (quantified using the combination index method) were a function of the dose ratio of the two drugs, and of overall treatment intensity. BCNU produced patterns of cell killing similar to CCNU, but showed little interaction with cisplatin. Our results suggest significant clinical potential in using CCNU with cisplatin, particularly since CCNU-cisplatin combinations were synergistic even in the cell subpopulations most resistant to each drug as a single agent. PMID- 2257226 TI - Expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer. AB - We examined the expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer by immunohistochemical staining using an anti-PSTI antiserum, an in situ hybridisation technique utilising sulphonated PSTI cDNA probe, and a Northern blot hybridisation method, using a 32P-labelled PSTI cDNA probe. Immunohistochemically, PSTI was detected in 80 of 95 (84%) colorectal cancer cases. Analyses with in situ hybridisation as well as Northern blot hybridisation demonstrated PSTI mRNAs in immunohistochemically positive cases, showing PSTI could be produced in colorectal cancerous cells. Histologically well or moderately differentiated adenocarcinoma showed higher incidence of PSTI immunoreactivity than the other types. Furthermore, the intensity of the immunohistochemical staining for PSTI increased the more cases advanced, particularly in regard to depth of invasion and tumour size. Thus, PSTI expression is widespread in colorectal cancer, and occurs more commonly in advanced cases. Considering the suggestion that PSTI is a growth-stimulating factor as an well as inhibitor to proteolytic proteinase, the present findings may indicate that PSTI expressed in colorectal cancerous cells may play a role possibly closely associated with tumour development. PMID- 2257227 TI - Reduced nuclear binding of a DNA minor groove ligand (Hoechst 33342) and its impact on cytotoxicity in drug resistant murine cell lines. AB - The reduced cellular uptake, and subsequent reduced nuclear availability, of cytotoxic agents is a factor in the resistance of mammalian cells to anti-cancer drugs that act by interaction with DNA. The whole cell uptake, nuclear binding and cytotoxicity of a DNA-specific ligand, Hoechst dye number 33342 (Ho342), has been studied in cytotoxic drug resistant variants of a murine tumour cell line. Cell lines showing various degrees of cross-resistance to adriamycin as a part of the phenotype of classical multi-drug resistance (MDR) demonstrated a reduction in intranuclear Ho342 content, up to a maximum of 35% of the level found in the parent as assessed by flow cytometry, despite similar levels of whole cell uptake determined using radiolabelled ligand. Ability to limit nuclear accessibility of Ho342 correlated closely with cellular resistance to Ho342 and to adriamycin. All drug resistant cell lines showed a significant increase in nuclear accessibility to Ho342 after verapamil treatment, including a methotrexate resistant cell line. The methotrexate resistant variant, not demonstrating MDR, showed reduced nuclear binding of Ho342 but increased cell kill associated with a propensity to develop a population of cells showing extra DNA replication in response to Ho342 exposure. Differences between cell lines in the relationship between Ho342 induced cell cycle perturbation and cell kill supported the conclusion that modulation of several pathways of response to cytotoxic agents had occurred in the development of drug resistance. PMID- 2257228 TI - Liposome-delivered Si(IV)-naphthalocyanine as a photodynamic sensitiser for experimental tumours: pharmacokinetic and phototherapeutic studies. AB - The pharmacokinetic behaviour and phototherapeutic effectiveness of bis(di isobutyloctadecylsil-oxy)-2,3-naphthalocyanatosilicon (iso-BOSiNc) incorporated into dipalmitoyl-phosphatidylcholine (DPPC) liposomes have been studied in Balb/c mice bearing an MS-2 fibrosarcoma. We found that iso-BOSiNc i.v.-injected at a dose of 0.5 mg kg-1 b.w. is preferentially transported by serum lipoproteins; in particular, the photosensitiser is associated with LDL (57.8% of total recovery in the serum) and HDL (35.7%) while minor amounts are associated to VLDL (2.63%) and other serum proteins (3.89%), Iso-BOSiNc concentrations greater than 1 microgram g-1 of tissue are recovered from the tumour at 12-48 h after administration while the ratio of iso-BOSiNc concentration in tumour and peritumoral tissue is greater than 10. Upon increasing the injected dose, the additional iso-BOSiNc is almost exclusively bound by HDL, which leads to large uptake of the photosensitiser by liver and spleen. The efficiency of iso-BOSiNc as a photodynamic agent was measured upon irradiation with a different dose-rate for a total light dose of 450 J cm-2. The extent of tumour necrotic area increases as a function of the time after the end of PDT treatment and reaches a maximum level after about 24 h. Moreover, the necrotic area is linearly dependent on the irradiation dose-rate up to 100 mW cm-2. In all there is substantial evidence that iso-BOSiNc delivered in a liposomal dispersion is a highly effective photosensitizer for PDT of tumours. PMID- 2257229 TI - The prognostic value of DNA-ploidy in colorectal carcinoma: a prospective study. AB - One hundred and fifty-seven patients with usual colorectal cancer were analysed prospectively for DNA-ploidy, DNA-index and S-phase fraction (SPF) using flow cytometry. An abnormal DNA-stemline was observed in 68% of tumours. The patients have been followed for a median of 36 months. In univariate analysis, tumour stage was the most significant prognostic factor. After excluding patients with stage D disease, DNA-aneuploidy was significantly associated with a shorter survival and a shorter disease free survival. SPF, however, did not correlate with prognosis. In multiple samples from the same tumour there was on average a 29% difference between the highest and the lowest SPF indicating considerable heterogeneity in proliferative activity within the tumours. In diploid tumours the variation was even higher. Patients with proximal tumours as well as female patients had DNA-diploid tumours more often than the others. This may indicate that there are different, so far unknown, aetiological factors leading to different types of ploidy pattern. PMID- 2257230 TI - Lung cancer among women in north-east China. AB - A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung. PMID- 2257231 TI - Are treatment strategies of urologic oncologists influenced by the opinions of their colleagues? AB - In a previous study, urologists, radiation oncologists and medical oncologists in Britain, Canada and the United States were asked to state how they would wish to be treated if they had urologic cancer as described in six clinical scenarios and whether they would agree to be entered in randomised clinical trials. This study disclosed major controversy regarding treatment options for each scenario and reluctance by these experts to enter randomised clinical trials. In the present study a second questionnaire which included a summary of the treatments selected initially was sent to the same 227 oncologists. Respondents were asked, in view of these additional information, how they would wish to be treated and whether they would enter themselves (or their patients) on randomised trials comparing the two treatment options most favoured by their colleagues. Most respondents did not modify their treatment preference. There was still poor agreement to enter themselves on trials (29%), but a higher proportion would offer such trials to their patients (45%). Thus the demonstration of controversy about optimum treatment did not influence personal bias, but could facilitate the entry of patients into trials that address major controversies. We conclude that treatment strategies of urologic oncologists are influenced minimally by opinions of their colleagues, but that the method of using surrogate questionnaires is a valuable aid to the design of clinical trials. PMID- 2257232 TI - Cancer incidence in migrants to New South Wales from England, Wales, Scotland and Ireland. AB - Cancer incidence in migrants to New South Wales (NSW) from individual countries within the British Isles has been compared with that in the Australian-born population using data from the NSW Central Cancer Registry for the period 1972 84. Indirectly age-standardised incidence ratios (SIR) showed that, for cancer at all sites combined, Scottish migrants had a significantly higher, and English migrants a lower, incidence than the native-born Australians. Melanoma of skin was less common in migrants from all four countries while lung cancer was more common. In all except the Irish migrants, stomach cancer was more frequent than in the Australian-born. Raised SIRs for bladder cancer were found in men from all the countries and for breast cancer in all except the Irish women but only in the English migrants were these ratios significant. English migrants differed from those from Wales, Scotland and Ireland in that, compared with the Australian born, they had significantly lower SIRs for cancer of the colon (both sexes), head and neck, larynx and prostate (men), gallbladder and kidney (women), and a higher SIR for ovarian cancer. Bone cancer was relatively more common in men born in Wales. 'Other genital' cancers (penis and scrotum; vulva and vagina) tended to be more frequent in migrants from each country than in the Australian-born. PMID- 2257235 TI - Proceedings of the XIV meeting of the International Study Group for Steroid Hormones. Rome, Italy, 30 November 2-December 1989. PMID- 2257234 TI - Regulation of proliferation, invasion and growth factor synthesis in breast cancer by steroids. AB - Endogenous ovarian estrogens and progestins appear to play a critical role in the development and progression of breast cancer. Local productions of growth factors probably also contribute to malignant proliferation, while production and activation of collagenolytic enzymes may be equally critical for local invasive processes. The current review focuses on characterization of growth factor receptor systems operant in normal and malignant breast epithelium. In addition, the determinants of local invasion are reviewed: attachment, modality, and proteose secretion. Finally, data are discussed concerning the regulation of both proliferation and invasion by hormones and antihormonal agents in hormone dependent breast cancer. The results suggest new potential pharmacologic targets to explore to suppress onset and progression of breast cancer. PMID- 2257233 TI - Cancer in children of epileptic mothers and the possible relation to maternal anticonvulsant therapy. AB - Cancer incidence among 3,727 offspring of women hospitalised for epilepsy in Denmark between 1933 and 1962 was evaluated in a record-linkage survey with the national cancer registry. The children were identified from hospital charts, population listings, and parish registries. For all children (born before and after their mothers' hospitalisation), no excess of cancer was found in comparison with the general population (49 observed vs 53.8 expected). Among the 2,579 children born after their mothers' first admission for epilepsy, and thus presumably exposed in utero to anticonvulsant drugs, 14 cancers were identified compared to 13.8 expected (relative risk 1.0; 95% confidence interval 0.6-1.7). Contrary to some previous reports, cancers of the brain and nervous system were not significantly increased (3 observed vs 2.2 expected). These data provide no evidence that anticonvulsant drugs are transplacental carcinogens, and indicate that overall increases in risk as high as 80% are unlikely. PMID- 2257236 TI - The significance of steroid metabolism in human cancer. AB - Epidemiological and clinical evidence suggests that steroid hormones are intimately involved in the natural history of many cancers, including those of the breast, endometrium and prostate. However, it has been difficult to demonstrate that progressive changes in tumour development are related to circulating levels of steroids. This may be because further metabolism of steroids occurs locally within the tumour and its adjacent host tissue. Using the breast as an example, data has been reviewed that such local metabolism may (a) markedly change the biological potency of steroid hormones and (b) be associated with the risk, presence, pathology, stage and hormone sensitivity of cancer. The implications of these findings are discussed including the need to identify factors which regulate steroid metabolism in peripheral tissue and tumours. In this way the potential to influence the microenvironment around and within tumour cells may be realized in favour of the patient. PMID- 2257237 TI - Aromatase inhibitors and hormone-dependent cancers. AB - Aromatase (estrogen synthetase) occurs in a variety of tissues. Using immunocytochemistry, we have recently located this enzyme in cellular compartments of several types of human tissue. Furthermore, we found the mRNA was located in the same structures where tested. As both gonadal and peripherally formed estrogen contribute to growth of hormone sensitive cancers, we have developed aromatase inhibitors to block synthesis of this hormone. We have determined that 4-hydroxyandrostenedione (4-OHA) selectively inhibits aromatase activity in ovarian and peripheral tissues and reduces plasma estrogen levels in rat and non-human primate species. 4-OHA was also found to inhibit gonadotropin levels and reduce estrogen and progesterone receptor levels in treated animals. The mechanism of these effects appear to be associated with the weak androgenic activity of the compound. These effects together with aromatase inhibition may result in a synergistic response reducing estrogen production and action. In postmenopausal women, estrogens are mainly of peripheral origin. When postmenopausal breast cancer patients were administered either daily oral or parenteral weekly treatment with 4-OHA at doses that did not affect their gonadotropin levels, plasma estrogen concentrations were significantly reduced. Complete or partial response to treatment occurred in 34% of 100 patients with advanced breast cancer, while the disease was stabilized in 12%. These results indicate that 4-OHA is of benefit in postmenopausal patients with advanced disease who have relapsed from prior hormonal therapies, and that steroidal inhibitors may be of value in premenopausal patients. PMID- 2257238 TI - New non-steroidal aromatase inhibitors: focus on R76713. AB - R76713 is a novel triazole derivative which selectively blocks the cytochrome P450-dependent aromatase. In human placental microsomes, in FSH-stimulated rat and human granulosa cells and in human adipose stromal cells, 50% inhibition of estradiol biosynthesis was obtained at drug concentrations of 2-10 nM. In PMSG injected female rats, R76713 lowered plasma estradiol levels by 50 and 90% 2 h after single oral doses of 0.005 and 0.05 mg/kg respectively. After 1 mg/kg, estradiol levels were suppressed by 90% for 16 h. In male cynomolgus monkeys, R76713 dose-dependently (0.03-10 micrograms/kg) inhibited peripheral aromatization with an ED50 of 0.13 microgram/kg without altering metabolic clearance rates and conversion ratios. In vitro R76713 had no effect on other P450-dependent steroidogenic enzymes up to 1000 nM at least. In rats, LHRH-, ACTH and sodium-deprived diet stimulated plasma testosterone, corticosterone and aldosterone levels were not modified 2 h after single oral administrations of R76713 (up to 20 mg/kg). Furthermore, R76713 did not show any in vitro or in vivo estrogenic or antiestrogenic property. R76713 also induced regression of DMBA induced mammary tumors after daily oral administration of 1 mg/kg b.i.d. In male volunteers (n = 4), a single oral dose of 5 and 10 mg lowered median plasma estradiol levels from 70 pM to the detection limit of the assay (40 pM) 4, 8 and 24 h after intake whereas no changes were detected after placebo administration. In premenopausal women (n = 15), receiving a single oral dose of 20 mg, median plasma estradiol levels decreased from 389 pM (before) to 168, 133 and 147 pM, 4, 8 and 24 h after intake whereas they remained above 420 pM after placebo (n = 7). PMID- 2257239 TI - Antiestrogen action in mammary cancer and in fetal cells. AB - The present data confirm the very complicity of the response of antiestrogen when this compound is studied in different experimental conditions. The new and potent antiestrogen ICI 164,384, which is considered as a full antagonist in most models studied, concerning the progesterone receptor in the isolated cells of the uterus and vagina of guinea-pig acts as a real agonist. However, this compound antagonizes cell proliferation, progesterone receptor, and decreases the concentration of estradiol in different hormone-dependent mammary cancer cell lines. Another interesting aspect is the response of the antiestrogen 4 hydroxytamoxifen which in isolated cells of very close tissues such as the uterus and vagina is an antagonist for the former and agonist for the latter concerning the progesterone receptor. In conclusion, the present data added new information in the complicity of the mechanism of action of antiestrogens, but using new models interesting possibilities are opened to understand their responses and their mechanism. PMID- 2257240 TI - 4-Aminoandrostenedione derivatives: a novel class of irreversible aromatase inhibitors. Comparison with FCE 24304 and 4-hydroxyandrostenedione. AB - FCE 24928 (4-aminoandrosta-1,4,6-triene-3,17-dione) was selected among a series of 4-aminoandrostenedione derivatives as a novel irreversible aromatase inhibitor. Its in vitro and in vivo properties have been studied and compared to FCE 24304 (6-methylenandrosta-1,4-diene-3,17-dione) and 4-OHA (4 hydroxyandrostenedione). FCE 24928 caused time-dependent inhibition of human placental aromatase with a t1/2 of 4 min and Ki of 59 nM. Enzyme inactivation by FCE 24928 was faster than by FCE 24304 (t1/2 13.9 min). In PMSG-treated rats, microsomal ovarian aromatase activity was reduced 24 h after FCE 24928 dosing by both the s.c. (ED50 1.2 mg/kg) and the oral (ED50 14.1 mg/kg) routes. The compound was more potent than FCE 24304 and 4-OHA (ED50 1.8 and 3.1 mg/kg s.c.). FCE 24928 did not show any interference with 5 alpha-reductase and desmolase activity nor any significant binding affinity for androgen and estrogen receptors. Slight binding affinity for androgen receptor was observed with FCE 24304 and 4-OHA (0.21 and 0.25% of DHT). In immature, castrated rats, FCE 24928 did not show any intrinsic androgenic activity, up to 100 mg/kg/day s.c., in contrast to a slight androgenic activity observed with FCE 24304 at 10 mg/kg s.c. PMID- 2257241 TI - Biochemical and pharmacological development of steroidal inhibitors of aromatase. AB - Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase both in vitro and in vivo. Several of these agents have exhibited higher affinity for the enzyme complex than the substrate. In order to examine further the interaction(s) of 7-substituted steroids with aromatase, biochemical and pharmacological studies were performed on 7 alpha-thiosubstituted androstenediones and 7-substituted 4,6-androstadiene-3,17-diones. Potent inhibition of aromatase activity in human placental microsomes has been observed with several new 7 alpha-thiosubstituted androstenediones. 7-Benzyl- and 7 phenethyl-4,6-androstadiene-3,17-diones effectively inhibited microsomal aromatase, with apparent Kis ranging from 61 to 174 nM. On the other hand, 7 phenyl-4,6-androstadiene-3,17-dione exhibited poor activity, with an apparent Ki of 1.42 microM. Similar inhibitory activity was observed with reconstituted, purified cytochrome P450Arom preparations. Additionally, these agents were evaluated for inhibition of aromatase activity in two human carcinoma cell lines, the MCF-7 human mammary cancer line and the JAr choriocarcinoma line. The 7 alpha thiosubstituted androstenediones and 7-substituted 4,6-androstadiene-3,17-diones produced dose-dependent inhibitions of aromatase activity in the cell cultures. The most effective inhibitors were the 7 alpha-substituted androstenediones, with EC50 values ranging from 7.3 to 105 nM. Finally, the JAr cell culture system exhibited prolonged inhibition of aromatase activity following exposure to 7 alpha-APTADD, suggesting enzyme inactivation by this inhibitor. Thus, these agents are effective aromatase inhibitors, and the results encourage further development of this group of medicinal agents for the treatment of estrogen dependent mammary carcinoma. PMID- 2257242 TI - Corticosteroids and the brain. AB - Mineralocorticoid (MR) and glucocorticoid receptors (GR) are expressed in the central nervous system. Radioligand binding studies, autoradiography, immunocytochemistry and in situ hybridization have shown that MR and GR are found in abundance in neurons of the limbic system (hippocampus), a structure involved in mood, affect and subtle control of the hypothalamic-pituitary-adrenal (HPA) axis. In the hippocampus MR binds corticosterone (CORT) as well as aldosterone (ALDO) with high affinity. MR seems mainly occupied by CORT in the face of its 2 3 order higher circulating concentration. GR binds CORT with a 6-10-fold lower affinity. MR and GR gene expression, as well as the native receptor proteins, seem to be controlled in a coordinative manner. When GR is down-regulated by excess homologous steroid, MR appears to be increased. Down regulation of MR reduces GR as well. MR and GR display a differential ontogenetic pattern. Ontogeny, particularly that of GR, can be permanently influenced when animals are exposed during the first post-natal week of maternal deprivation, handling, CORT or ACTH1-24 injections. These MR and GR changes persist into senescence and have been proposed to result in altered CORT responsiveness, stress regulation, behavioural adaptation and brain aging. PMID- 2257243 TI - Neurosteroids: a new brain function? AB - The biosynthesis of neurosteroids proceeds through cholesterol side-chain cleavage, and gives rise to pregnenolone (P) and dehydroepiandrosterone (D). These steroids accumulate in the rat brain independently of the supply by peripheral endocrine glands. This led to the discovery of a steroid biosynthesis pathway in rat brain oligodendrocytes based on enzyme immunocytochemistry and conversion of radioactive precursors to C-21 steroids. Several biological functions have been proposed for P and D. They may serve as precursors of other steroids (such as progesterone and testosterone and their metabolites). They are implicated in the control of some behavioural activities. They have excitatory effects on neurons, and they modulate the function of GABAA-receptors. These observations may apply to all mammalian species including the human, and the physiological significance of neurosteroid synthesis needs further investigation. The relationship between steroids and cerebral function may be reconsidered in the light of a new fact: the existence of a biosynthetic pathway of these compounds from cholesterol, assured in the brain by the oligodendrocytes, glial cells which synthesize myelin. PMID- 2257244 TI - Hippocampal glucocorticoid receptor and behavior: a correlative study in rats and mice. AB - A correlation has been demonstrated between binding capacity for [3H]corticosterone in the hippocampus and the performance in passive and active avoidance in the rat, and impaired behavior in adrenalectomized rats by exogenous corticosterone is restored. On this basis we have studied the possible correlation between strain-dependent behavioral differences and the glucocorticoid binding capacity in the hippocampus in mice and rats. In Naples high- (NHE) and low-excitability (NLE) rat strains, genetically selected on the basis of divergent locomotor activity upon forced exposure to a spatial novelty situation, no differences were found in glucocorticoid maximal binding capacity while both strains had a lower capacity than Naples random-breed (NRB) control rats. However, the intra-strain correlative analysis of hippocampal glucocorticoid receptors number and behavioral scores demonstrated that motor and emotional indexes of arousal to novelty were positively correlated in NLE-and negatively in NHE- while no correlation was present in NRB rats. Using two inbred strains of mice, C57BL/6 and Balb/c, extensively investigated for learning abilities, the lower active avoidance score of C57BL/6 was associated with a lower binding capacity for [3H]corticosterone in the hippocampus. Altogether the above results support the involvement of the hippocampal glucocorticoid receptor in the modulation of some adaptive behavioral responses, while do not prove that genetic differences in behavior rest on parallel differences in binding capacity for glucocorticoid hormone. PMID- 2257245 TI - Neuroendocrine regulation of pulsatile luteinizing hormone secretion in elderly men. AB - Leydig cell function is driven by LH, secreted in a pulsatile manner by the anterior pituitary in response to episodic discharge of hypothalamic LHRH into the pituitary portal circulation, under control of a yet to be defined neural mechanism, the "hypothalamic LHRH pulse generator". The normal aging process in elderly men is accompanied by a decline in Leydig cell function. Whereas primary testicular factors undoubtedly play an important role in the decrease of circulating (free) testosterone levels with age, recent studies demonstrated that aging also affects the central compartment of the neuroendocrine cascade. Hypothalamic alterations comprise changes in the regulation of the frequency of the LHRH pulse generator with an inappropriately low frequency relative to the prevailing androgen impregnation and opioid tone, and with an increased sensitivity to retardation of the LHRH pulse generator by androgens. As observed by some authors in basal conditions and by others after endocrine manipulations. LH pulse amplitude seems also to be reduced in elderly men as compared to young subjects. This is most probably the consequence of a reduction in the amount of LHRH released by the hypothalamus. Indeed, challenge of the gonadotropes with low, close to physiological doses of LHRH in young and elderly men reveals no alterations in pituitary responsiveness when looking at either the response for immunoreactive LH or bioactive LH. Deconvolution analysis on data obtained after low-dose LHRH suggests a markedly prolonged plasma half-life of LH in elderly men, a finding which may explain the paradoxical increase of mean LH levels in face of the reduced or unchanged frequency and amplitude of LH pulses. PMID- 2257246 TI - Hormonal stimulation of bone cell proliferation. AB - The recent demonstration of estrogen receptors in bone derived cells has stimulated the study of direct effects of sex steroids on bone. We have shown direct stimulation of proliferation by 17 beta-estradiol (E2) of ROS 17/2.8 rat osteogenic osteosarcoma cells, and other bone-derived cells in culture, as well as sex-specific stimulation of diaphyseal bone in vivo by estrogen and testosterone, using [3H]thymidine incorporation into DNA and stimulation of the specific activity of creatine kinase as markers. ROS 17/2.8 cells were used as models of osteoblast-like cells to study the reciprocal modulation of stimulation of bone cell proliferation by sequential treatment by sex steroid and calciotrophic hormones. Pretreatment with 1,25(OH)2D3 and PTH augmented stimulation by E2, while pretreatment with PGE2 followed by E2 resulted in no additional stimulation. Reciprocally, pretreatment with E2 significantly reduced the response to PGE2 while showing an insignificant effect on the response to the other hormones. Gonadectomized Wistar-derived rats provided a useful model system for study of postmenopausal osteoporosis. In diaphyseal bone, [3H]thymidine incorporation and creatine kinase activity decreased 4 weeks after gonadectomy. At that time, a single i.p. injection of E2 in females, and testosterone in males, resulted in a highly significant increase in both these parameters within 24 h. PMID- 2257247 TI - Changes in hepatic androgen sensitivity and gene expression during aging. AB - The hepatic tissue of the male rat exhibits a gradual decline and ultimate loss in androgen responsiveness during in vivo aging. Appearance of the age-associated androgen insensitivity can be delayed by dietary calorie restriction, an effective means for life-span extension. The androgen receptor mRNA is detectable in the liver only in its androgen-responsive state. Pubertal appearance of hepatic androgen sensitivity is remarkably correlated with the concomitant appearance of a cytoplasmic androgen binding (CAB) protein. Androgen resistance during senescence is associated with the loss of hepatic CAB activity as well. We are investigating the molecular basis for the temporal modulation of this hormone sensitivity through studies on the differential expression of two androgen responsive marker genes. These are the androgen-repressible SMP-2, and the androgen-inducible alpha 2u-globulin. Androgen resistance of hepatocytes during aging results in repression of the alpha 2u-globulin gene, and derepression of the SMP-2 gene. The structural organizations for both of these genes have been characterized. The role of nuclear transcription factors (androgen receptor and any other transacting factor(s) which may be involved) in the coordinate regulation of alpha 2u-globulin and SMP-2 during aging and nutritional manipulation is being explored to establish the molecular mechanism of andropause in the liver. PMID- 2257248 TI - Hormonal prevention and treatment of osteoporosis--state of the art 1990. AB - Osteoporosis is a growing disease, and attention should be directed to possible means of preventing and treating this disease. Osteoporosis may be caused by a number of diseases (secondary osteoporosis), but it most often occurs in otherwise healthy persons. The major risk factors are a low bone mass at skeletal maturity, and a rapid bone loss. Postmenopausal bone loss may be prevented by hormone replacement therapy. All types of oestrogens and all administration forms are effective, as long as a sufficient serum concentration is obtained. The greatest benefit of hormone replacement therapy is obtained if instituted right after the menopause, when the bone loss is most rapid. But oestrogen will also arrest the bone loss when instituted much later in life. PMID- 2257249 TI - Calcitonin, estrogens and the bone. AB - Estrogen deficiency following natural or surgical menopause, is thought to be the main factor leading to postmenopausal bone loss. Furthermore, after estrogen failure a significant reduction of intestinal calcium absorption and a negativization of calcium balance has been observed. The mechanism of estrogen effect on skeletal tissue is not yet fully elucidated. Recently, specific receptors for estrogens in osteoblastic cells have been described; however their low density does not give a full explanation about their functional role. Therefore estrogens act, at least in part, indirectly through calciotropic hormones. In order to further elucidate this issue, we performed some studies in postmenopausal osteoporotic patients and in fertile oophorectomized women. In the first double blind placebo controlled study, after a 1-year estrogen treatment period we observed an increase in bone mineral content in the hormone-treated patients. Furthermore, in all treated patients an improvement of intestinal calcium absorption was detected, while 1,25-dihydroxy-vitamin D serum levels did not show significant changes. To further analyse the relationship between estrogens (E) and calcitonin (CT) in postmenopausal osteoporosis, we performed a double blind placebo controlled study to evaluate the effects of 1-yr estro progestative treatment on CT secretory reserve, evaluated by calcium infusion test. Blood levels of CT showed a progressive increase during the study period in the hormone-treated group, with a significant increase in the CT response to calcium stimulation test, suggesting a modulation of CT secretion by E. Recently, we performed two studies in fertile oophorectomized women. In the first, we followed longitudinally 24 fertile women for 1 yr. In these patients we measured, before and after oophorectomy, biochemical indexes of bone metabolism and bone mass. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. In the second study, performed on 14 women before and 6 months after oophorectomy, a treatment with conjugated estrogens allowed the correction of the primary intestinal defect responsible for the reduced calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2257250 TI - The effects of oophorectomy on skeletal metabolism. AB - The effects of oophorectomy on the biological indices of bone remodelling and the time-course of their changes are described. In the first few months following surgical menopause the measurement of the markers of bone remodelling indicates that the increase in osteogenesis is delayed compared with that of bone resorption; this prevalence of destruction over new bone deposition justifies the deficiency of skeletal balance, shortly after acute oestrogen deficiency. The changes in bone remodelling are accompanied by an increase in serum calcium while serum immunoreactive parathyroid hormone levels remain unchanged or even decrease, suggesting a shift to right of the parathyroid gland set-point. The reasons for the negative skeletal balance after oophorectomy might be sought therefore at bone tissue level, even if changes in responsiveness and/or of the parathyroid gland set-point could also be contributory. PMID- 2257251 TI - Pathophysiology of bone loss in castrated animals. AB - The pathophysiology of bone loss in castrated animals is reviewed. Both male and female rats rapidly lose metaphyseal trabecular bone from the tibia and the femur due to an imbalance between bone resorption and bone formation. The aetiology of sex hormone deficiency-induced bone loss is not fully understood. It seems unlikely that the bone loss is due to changes in the circulating levels of the calciotropic hormones or to an increase in the spontaneous release from peripheral blood monocytes of the bone resorption stimulating cytokine IL-1. Changes in the sensitivity of bone of castrated rats to calciotropic hormones may play a role as well as the lack of direct stimulatory effects of gonadal oestrogens and androgens on bone cells. In addition several data indicate that prostaglandins may be involved. PMID- 2257252 TI - Excimer lasers--a place in optometry? PMID- 2257254 TI - Classification and terminology of laser corneal surgery: making sense of keratospeak III. PMID- 2257253 TI - Will the excimer laser resolve the unsolved problems with refractive surgery? PMID- 2257255 TI - Myopic excimer laser photorefractive keratectomy: an analysis of clinical correlations. AB - In this study, we examined the correlations among various factors that may affect the results of central photorefractive keratectomy for myopia. Data analyzed from our studies of blind, partially sighted, and normally sighted eyes included patient age, attempted correction, time to re-epithelialization, postoperative corneal clarity, refraction (relative spherical equivalent), and uncorrected visual acuity. We found that larger attempted corrections resulted in less accurate refractions and poorer uncorrected visual acuity. Older patients tended to have better results than younger patients, regardless of the amount of attempted correction. The relationship between the amount of attempted correction and corneal clarity was weak. There was a statistical correlation between corneal clarity scores and uncorrected visual acuity, but the range of corneal clarity scores was small and even the highest scores were probably not in the range that interfered with vision, so the relationship was probably not causal. The rate of epithelial healing did not appear to affect either refractive or visual results, and was not affected by patient age. These findings may be useful in guiding future efforts to improve the results of this new surgical procedure for the correction of refractive error. PMID- 2257257 TI - Laser thermokeratoplasty by means of a pulsed holmium:YAG laser for hyperopic correction. AB - A new technique of hyperopic correction similar to radial thermokeratoplasty is presented. A pulsed Holmium:YAG laser was used, emitting a wavelength of 2.06 microns. The laser light was guided by a quartz fiber and focused by means of a handpiece. Eight of 16 coagulations located on rings concentric to the pupil resulted in central corneal steepening. The refractive change increased with the applied pulse energy above a threshold of about 10 mJ per pulse and was constant between 15 and 35 mJ per pulse. The effect decreased linearly with greater distance from the center. Four blind human eyes demonstrated that the parameters evaluated in the human cadaver eyes can be transferred to the living eye. Immediately after surgery, folds in Descemet's membrane parallel to the limbus appeared. With time, they gradually diminished but were still persistent after 4 months. Hyperopic changes of up to 5.00 diopters were obtained, remaining stable for 4 months. PMID- 2257256 TI - Myopic excimer laser keratectomy: a preliminary report. AB - Six patients underwent excimer laser refractive keratectomy for the correction of myopia. All eyes, with the exception of patient 6, who underwent a previous failed epikeratophakia procedure and subsequent removal of the lenticule, had normal baseline ophthalmologic evaluations and best corrected visual acuities of 20/25 or better. Spherical equivalents ranged between -5.50 and -12.00 diopters. Under topical and peribulbar anesthesia, the central corneal epithelium was removed. The delivery system of the laser was programmed to ablate corrections onto the central 5.0 mm of the cornea that would result in approximate emetropia. Moderate fluctuation of refractive and topographic parameters was noted during the period of epithelial healing and remodeling. At the 12th postoperative week, five of the corneas were clear on biomicroscopic evaluation with best corrected acuities of 20/20. The final patient, who was noncompliant in the use of topical corticosteroid therapy, developed a central, 2-mm opacity and resulting best corrected acuity of 20/40. Overall, the group demonstrated that myopic excimer laser photorefractive keratectomy is consistent with good wound healing, insignificant corneal scarring, a stable refractive correction, and excellent visual acuity. PMID- 2257258 TI - Corneal wound healing in monkeys 18 months after excimer laser photorefractive keratectomy. AB - Excimer laser keratomileusis (photorefractive keratectomy, direct corneal ablation) for myopic corrections of 2.00 diopters (n = 1), 4.00 D (n = 4), and 8.00 D (n = 3) was performed on eight corneas of four Rhesus monkeys. All animals were followed for 18 months. The ablations healed normally and no epithelial erosions occurred. Serial slit-lamp microscope examinations revealed that a variable amount of corneal haze developed in all animals; this haze progressively faded during the follow-up period. Histopathology revealed an epithelium of normal thickness, basement membrane abnormalities, increased number and activity of stromal keratocytes, and a variable amount of newly secreted extracellular matrix in the anterior stroma. These findings suggest that excimer laser keratomileusis induces a mild wound healing response in the anterior cornea which displays considerable individual variability and persists up to 18 months. PMID- 2257259 TI - Evaluation of an opacity lensometer for determining corneal clarity following excimer laser photoablation. AB - The appearance of haze in the central cornea following photoablation with a 193 nm excimer laser is an important factor in the postoperative course of this procedure. Data from 37 human eyes treated with photorefractive keratectomy, 4 eyes treated with phototherapeutic keratectomy, and 5 untreated eyes were used to evaluate the ability of a commercially available opacity lensometer to provide an objective measure of corneal clarity. We found that the opacity lensometer was able to detect light scattered from the cornea but was not sufficiently sensitive to distinguish reliably among excimer-treated eyes with degrees of corneal haze evaluated as clear, trace, or 1+ by slit-lamp microscope examination. In untreated, clear corneas, the values obtained with the opacity lensometer in eyes measured with and without a clear contact lens were within one unit of each other for any given eye, but values from eye to eye varied over a range of six units. In a test simulating different amounts of corneal haze using contact lenses evenly coated with nail polish enamel, the log-transformed opacity lensometer values varied directly with percent light scattering as determined by spectrophotometry. These results suggest that the opacity lensometer measurements are reliable and reproducible, but that in the human cornea something is being measured by the opacity lensometer that is not taken into account in clinical slit-lamp microscope evaluation. Overall, it appears that, in its present form, this instrument is not useful to measure corneal clarity after excimer laser photoablation. PMID- 2257260 TI - Excimer laser phototherapeutic keratectomy for a corneal nodule. PMID- 2257261 TI - A new technique for transscleral fixation of a posterior chamber intraocular lens in the absence of capsular support during penetrating keratoplasty. AB - In the setting of penetrating keratoplasty for the rehabilitation of aphakic or pseudophakic bullous keratopathy, a posterior chamber intraocular lens is frequently implanted in the absence of capsular support. Some surgeons have advocated transscleral fixation over iris fixation of the intraocular lens. Problems faced during such a procedure, however, include the obstructed approach of the suture needle behind the iris, and the exposed or eroded knot of the polypropylene suture. To circumvent both problems, we propose an ab externo technique that takes advantage of the work of Duffey et al and avoids the use of partial thickness scleral flaps. PMID- 2257262 TI - Development of the excimer laser in ophthalmology: a personal perspective. PMID- 2257263 TI - Corneal topography and optical zone location in photorefractive keratectomy. AB - Optical zone diameters in photorefractive keratectomy are small in order to minimize the depth of stromal tissue excision and, possible, the resultant stromal scarring. A small optical zone demands accurate placement on the corneal surface. This article reviews the principles that are important to location and measurement of the optical zone in photorefractive keratectomy. The ablated area should be centered on the cornea overlying the entrance pupil while the patient is fixating coaxially with the surgeon. An optical zone that is too small or decentered may decrease acuity, lessen contrast sensitivity, or produce glare, either on the fovea or on the perifoveal retina. The relationship between optical zone size and location and quality of vision is not yet known. Studies of this relationship will require videokeratography to locate the optical zone and its relationship to the entrance pupil, a capability that current videokeratoscopes do not possess. PMID- 2257264 TI - Should an ophthalmologist in private practice consider purchasing an excimer laser? PMID- 2257265 TI - Help! My final refraction did not agree with my alpha-scan. PMID- 2257266 TI - Damage to the corneal endothelium using anterior chamber intraocular lenses for myopia. PMID- 2257268 TI - [Design and verification of a registry and reference model for computers applied to oral pathology]. AB - The datum obtained during a retrospective review of the biopsies elaborated in the field of Oral Histopathology at ENEP Zaragoza, during a period of four years, were prosecuted within a computer registration model, where it was demonstrated their application in a National Reference Center of Oral Pathology. PMID- 2257267 TI - AMO's myopic epi keratoplasty lenticules. PMID- 2257269 TI - [Colorimetric and opacity percentage study of dental restorative resins]. AB - A colorimetric and opacity percentage study was carried out to compare experimental prototypes of resin at different die and additive concentrations with commercial prototypes. A simple and reproducible method was used. Through this study the optimum die and optical brightener formulas for a new dental resin were found and compared with available commercial dental resins in the national market. PMID- 2257270 TI - [Effect of rapid maxillary expansion on respiratory problems: 10-year retrospective study]. AB - Rhinomanometric studies have demonstrated that the maxillary fast expantion (ERM) reduces the nasal resistance of the air conduct and thus achieving the normal limits, in must cases. The hypotesis is that breathing will change from buccal to nasal, concluding that the nasal defense mechanisms (filtration, humidification and warming of inhaled air) will reduce some respiratory pathologies. PMID- 2257272 TI - [Dental caries in an animal model]. AB - Sprague-Dawley rats were inoculated with Streptococcus mutans (serotype g) and the effect of different concentrations (20, 40 and 56%) of sucrose in the diet on the establishment of this strain into the oral cavity of rats was studied. The Streptococcus mutans was well established in all the experimental groups and we found an almost linear correlation between the sucrose concentration and the severity of dental caries. Another factor that played an important role on the establishment of Streptococcus mutans into the mouth of rats was the inoculum size used. In this work a concentration of 4 x 10(10) showed a consistent establishment onto the teeth of this animal model. PMID- 2257271 TI - [Current use of miniplates in maxillofacial surgery. Review of the literature]. AB - Some of the European countries have advocated the use of monocortical screw miniplates for osteosynthesis in the craniofacial areas and there are several advantages over the wired osteosynthesis. The advantages and different applications of the miniplates in maxillofacial surgery are presented. PMID- 2257273 TI - [Mandibular and maxillary alveolar atrophy. Comparative analysis by sex, topography and seriousness of problem]. AB - Maxillary and/or mandibular osseous alveolar reabsorption that occurs after teeth loss is a continuous and irreversible process that, in authors opinion, seems to affect more women than men and more the mandible than the maxillary. In our country the epidemiologist profile of the problem is unknown and previous published studies at this respect was not found by this author in domestic literature. In this paper maxillary mandibular Alveolar Atrophy Syndrome characteristics are studied in a group of patients of the Departamento de Cirugia de la Escuela de Odontologia de la Universidad del Bajio on the perspective of its prevalence in relation of sex, problem seriousness and its topography. PMID- 2257274 TI - [Physical behavior of 5 autopolymerizing dental resins]. AB - The Tests described in the American Dental Association Standard No. 27 were carried out with five commercial dental resins available in mexican market. These are: Adaptic, Concise, Miradapt, Degufill and Finesse. Two of them are of the macrofilled type (II), one is of the hybrid type (mix of macro and micro particles; type II) and two of the microfilled type (I). All the resins tested met satisfactorily the specifications of the A.D.A. standard No. 27 for dental componsed resins, according with their classification. PMID- 2257275 TI - Human glutathione S-transferases: radioimmunoassay studies on the expression of alpha-, mu- and pi-class isoenzymes in developing lung and kidney. AB - The developmental expression of the alpha-, mu- and pi-class glutathione S transferases has been defined in human lung and kidney using radioimmunoassay, immunohistochemistry and column chromatography. Expression of alpha-class enzymes increased significantly after about 40 weeks gestation in kidney but not lung, while expression of mu isoenzymes was continuous throughout development in both tissues. Expression of the pi isoenzyme fell during in utero ontogeny in lung, the pattern of down-regulation being similar to that previously observed in liver. There was no change in the expression of this isoenzyme in kidney. Comparison of the expression of the glutathione S-transferases in developing lung, kidney and liver shows some common patterns of expression suggesting these genes are under similar regulatory control. PMID- 2257276 TI - Reduction of extracellular methemoglobin by erythrocytes. AB - Erythrocytes, suspended in a glucose-containing buffer, catalyzed the partial reduction of extracellular methemoglobin. Physiological concentrations of ascorbic acid or dehydroascorbic acid greatly enhanced the rate of reaction and the ultimate extent of reduction. The relationship between erythrocyte concentration and initial reaction rate was nonlinear, which suggested that the rate limiting factor was not an erythrocyte membrane enzyme. Also, significant dehydroascorbate-stimulated reduction occurred even when the erythrocytes and methemoglobin were separated by a dialysis membrane. The above observations indicate that the transfer of reducing equivalents across the erythrocyte membrane and reduction of extracellular methemoglobin can be accomplished by release and recycling of ascorbic acid. PMID- 2257278 TI - A matrix protein of Mr 55,000 that accumulates in human articular cartilage with age. AB - Adult human articular cartilage contains a protein of Mr 55,000 which is deficient in newborn cartilage. In the adult the molecule represents one of the most abundant non-collagenous, non-proteoglycan molecules in 4 M guanidinium chloride extracts of the tissue. The molecular size of the protein on SDS-PAGE remains constant under reducing and non-reducing conditions, suggesting that it does not exist as a disulphide-bonded multimer, nor do intramolecular disulphide bonds greatly influence its conformation. The protein has the ability to interact with some immunoglobulin preparations making its detection possible by Western blotting with some non-specific antisera. Labeling with [3H]leucine in organ culture indicates that protein of this size is being made by the chondrocytes. However, during purification the newly synthesized molecules do not behave as the resident protein on ion-exchange chromatography, suggesting that the protein may accumulate with age rather than being a major synthetic product of the adult chondrocytes. Amino terminal protein sequence analysis indicates that the N terminus of the protein is blocked. Sequences derived from peptides generated with cyanogen bromide do not show homology with previously characterized proteins. Molecules of a similar size and composition have been described in bovine cartilage. PMID- 2257277 TI - pH-sensitive, Ca2+/calmodulin-dependent phosphorylation of unique protein in molluscan nervous system. AB - Intracellular pH and Ca2+ are prominent co-regulators of neuron excitability that act on ion channels. In looking for a possible mechanism of their action, we tested their combinatorial effect on the phosphorylation state of nervous system proteins. 32PO4 labelling in endogenous phosphorylation reactions of homogenates of nervous tissue of the sea-slug Pleurobranchaea showed steep pH sensitivity in protein migrating at a molecular mass of 108 kDa with pI 6.9-7.0 (pp108). Phosphorylation of pp108 was highest below reaction pH 7.0 and declined steeply as pH rose to 7.4 pp108 phosphorylation was Ca2+/calmodulin-dependent. pp108 constituted a significant part of the total protein (0.15%) and phosphoprotein (8.9%) of the nervous system. The specifically and uniquely combinatorial pH and Ca2+ sensitivity of the phosphorylation of pp108, and its relative abundance, suggest that it could mediate integrated actions of H+ and Ca2+ in the molluscan neuron. PMID- 2257279 TI - Characterization of the S'-subsite specificity of V8 proteinase via acyl transfer to added nucleophiles. AB - The S'-subsite specificity of endoproteinase Glu-C (V8 proteinase) was studied by acyl transfer reactions using Z-Glu-OMe as acyl donor and a series of amino acid- and peptide-derived nucleophiles. The partition constant, which characterizes specificity, was determined by a method based on the integrated rate equation. V8 proteinase prefers amino acid residues with hydrophobic side chains in the P'1 position. Di- and tripeptide amides are more efficient nucleophilic amino components than amino acid amides. PMID- 2257280 TI - Collagens as multidomain proteins. AB - The number of proteins known to contain collagen-like triple helical domains is rapidly increasing. The functions of these domains are to provide molecular rods that separate spatially non-triple helical domains with varied properties and structures and to permit lateral interactions between molecules. Two-thirds of the amino acids of the triple helical domains have their side-chains at the surface of the protein. The triple helix is also a structure that is easily predictable from the primary structure. The structure of several recently discovered collagens are discussed in terms of domains and functions. The triple helical domains have sizes varying from 33 to over 1,000 amino acid residues. The longest uninterrupted triple helices are involved in the formation of the classical quarter-staggered fibrils. Other triple helical domains permit varied molecular aggregates. A very broad spectrum of non-triple helical or globular domains are interspersed by triple helices. Only those located at the extremities of the molecules are large in size, sometimes several hundred kDa, while the domains separating 2 triple helices are small (less than 50 amino acids) and provide the molecules with hinges, proteolytic cleavage sites or other specialized functions like a glycosaminoglycan attachment site. If the assembly of the 3 chains required for the triple helix formation can be controlled in vitro, collagen-like molecules offer an as yet unexploited potential for protein engineering. PMID- 2257281 TI - Generalized gradient schemes for the measurement of two-dimensional image motion. AB - This paper describes a procedure for recovering the global velocity of an image by incorporating spatial filtering, and optionally, temporal filtering, into a scheme that employs a generalized version of the gradient algorithm of motion detection. Motion within a patch is analysed by six parallel channels, each incorporating a different spatiotemporal filter. Advantageous features of this scheme are: (a) global velocity is derived directly, without first computing local velocity at a number of image locations; (b) the filters compute first derivatives rather than second derivatives, making the scheme potentially more resistant to noise than certain other schemes; (c) two of the six filters can be chosen almost completely arbitrarily, and can therefore be tailored to maximize signal reliability, and (d) the measurement of velocity can be made as local or as global as desired by altering the size of the patch that is viewed by the filters. An analogous scheme is derived for the measurement of rotation as well as expansion or contraction of the image. PMID- 2257282 TI - On ringing limits of the auditory periphery. AB - In classical hearing theory frequency and time have been treated as nearly independent acoustical dimensions. In this paper the interaction between temporal and spectral aspects is studied. An important determinant in this respect is the filtering of auditory stimuli in the cochlea. A view of auditory filtering that is balanced in frequency and time is obtained from the 'reverse-correlation function', abbreviated: revcor function. This function is derived from the response of an auditory-nerve fibre to a white-noise sound stimulus. It is a useful descriptor of peripheral filtering for a wide class of stimuli in which effects of nonlinear distortion are of minor importance. Measured revcor functions can be approximated by a standard mathematical function of which the parameters have a clear meaning. For these functions the spread in time and in frequency are uniquely related to one another. This relation is carried over to the case of cochlear filtering and applied to two important cases: stimulation by signals with small and with large amplitude variations. The results turn out to be markedly different in these two cases. In the final section the relevance of the results to various other fields of auditory research is discussed. PMID- 2257283 TI - The impact of fluctuations on the recognition of ambiguous patterns. AB - The recognition of ambiguous patterns by humans is modelled by coupled differential equations which describe the formation of percepts by means of order parameters which in turn are determined by the saturation of attention parameters. We study the impact of fluctuations on the attention parameters and thus indirectly on the recognition of ambiguous patterns. Excellent agreement with psychophysical experimental results by Price on the transient behaviour of switching times and by Borsellino et al. on the distribution function of switching times as function of the size of the visual field is obtained. Our model allows us to deal also with the shift of width and position of the distribution function with respect to slow and fast observers in the sense of Borsellino. PMID- 2257284 TI - [Effect of central coordination in the sense of v. Holst on the control of breathing and limb movements in humans]. AB - We found modulations in the time-course of breathing during rhythmic abduction adduction movements in shoulder and hip joints which can be interpreted as phenomena of central coordination in the sense of v. Holst. They occurred in more than 75% of the recorded breaths. The strength of this coordination depends on number and kind of limbs moving rhythmically and on the use of an acoustic trigger signal ("Zeitgeber") for the limb rhythm as well. Our findings indicate that reactions of the respiratory apparatus cannot be regarded only in connection with its homeostatic function and with mechanical influences. Breathing control appears integrated in the whole organism's "motor control system". Therefore, an influence of breathing movements on other motor processes is possible as well. Coordination leads to a stable temporal order between breathing and additional movements. Its possible advantage could be an energetic economization as may be concluded from analogous phenomena in coupled non-linear oscillators. PMID- 2257285 TI - Cardiovascular response to unilateral electroconvulsive therapy. AB - Few studies have examined the cardiovascular response to pulse unilateral electroconvulsive therapy (ECT) performed using modern techniques. In this study of 30 patients (mean age 62 years) with major depression, we determined the effects of pulse unilateral ECT on cardiac work load using the rate-pressure product (RPP), a product of pulse and systolic blood pressure. The mean RPP across all ECT treatments increased by an average of 96% from pre-ECT baseline, with the maximal RPP occurring typically during the seizure. The amount of increase in RPP did not differ significantly over the course of treatments. The increase in RPP was significantly and inversely related to baseline RPP, such that subjects with the highest baseline RPPs actually had smaller increases in RPP during the ECT treatments. The mean percent change in RPP was not associated with age, sex, presence of cardiovascular disease, ECT stimulus charge, EEG seizure duration, or amnestic side effects. There was a trend (p = 0.06), however, for the mean increase in RPP to be greater in responders (100% increase, n = 25) than in nonresponders (76% increase, n = 5). The potential relationship of clinical outcome to the increase in RPP suggests that both factors may be manifestations of the physiological intensity of the ECT-induced seizure. PMID- 2257287 TI - Brainstem auditory-evoked potentials to different rates and intensities of stimulation in schizophrenics. PMID- 2257286 TI - Story recall under monaural and binaural conditions in psychiatric patients. AB - It has been reported that a large proportion of patients with major psychiatric disorders can recall a short story better if they listen with one ear rather than the other (monaural asymmetry), and that binaural performance is worse than with the better ear alone (binaural inferiority). Blocking the poorer ear with an earplug is said to significantly improve speech comprehension in daily life. Because of the theoretical and practical significance of these reports, we have attempted a replication. Forty-four psychotic patients, primarily schizophrenic, were studied. We found a lower incidence of abnormal monaural asymmetry and binaural inferiority than was previously reported. The incidence remained low whether we considered the entire sample or subgroups defined by diagnosis, chronicity, or age. Retest reliability was poor. We also found that binaural superiority was as common as binaural inferiority, and concluded that the instances of relative binaural inferiority in our sample were primarily due to chance. Differences in methods, subject selection, or medication were considered, but did not clearly account for the discrepancies between our results and previous studies. Future research must focus on establishing the conditions determining reliability. PMID- 2257288 TI - Hyperprolactinemia and risk for relapse of cocaine abuse. PMID- 2257289 TI - Water intoxication treatment. PMID- 2257290 TI - Olfactory sense in psychoses. PMID- 2257291 TI - Antimicrobial polypeptides of human neutrophils. PMID- 2257292 TI - Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice. AB - We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment. PMID- 2257293 TI - Direct relationship between remission duration in acute myeloid leukemia and cell cycle kinetics: a leukemia intergroup study. AB - Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine. Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR). Older patients appeared to have more rapidly cycling cells (P = .003). No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease. However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration. CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B). Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600. Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04). We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy. PMID- 2257294 TI - Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity. AB - Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity. Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed. This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose dependent manner, without Urd-related toxicity. In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg/mL), the continued administration of AZT plus daily BAU (300 mg/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis. When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity. In vitro, at a concentration of 100 mumol/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells. The clinical and biochemical implications of these findings are discussed. PMID- 2257296 TI - Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias. AB - In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life. PMID- 2257295 TI - Different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice. AB - It has been reported that in vitro uridine (Urd) can reverse azidothymidine (AZT) cytotoxicity without decreasing anti-human immunodeficiency virus (HIV) activity. Our studies in mice have shown that daily oral doses of benzylacyclouridine (BAU), an inhibitor of Urd breakdown, also reduces AZT hematologic toxicity, presumably by elevating the plasma concentration of Urd. We now extend these murine studies and report the effect of various doses of exogenous Urd, various doses of BAU, or the combination of BAU and Urd, administered daily, on AZT induced toxicity. In mice receiving concomitant AZT, daily doses of Urd of 1,000 to 2,000 mg/kg increase peripheral reticulocytes and slightly reduce AZT-induced hematologic toxicity. However, the range of effective doses is narrow, and higher doses of Urd (greater than 3,000 mg/kg/d) significantly enhance hematologic toxicity. At its most effective dose, (2,000 mg/kg/d), Urd produces 28% mortality. In contrast, BAU doses up to 300 mg/kg/d reduced AZT-related hematologic toxicity in a dose-dependent manner without mortality. Higher daily doses of BAU and the combination of BAU with low doses of Urd were not more effective. Studies conducted in mice infected with the Rauscher murine leukemia virus (RLV) indicate that BAU does not impair the antiretroviral effect of AZT when administered at doses that reduce AZT-induced anemia and leukopenia. These findings may be significant for the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. PMID- 2257297 TI - Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene. AB - To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL-3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter than the human protein. Protein homology was found to be 89.5% for the signal peptide (19 aa) and 80.5% for the mature protein (124 aa). Comparison of the human and RhIL-3 coding sequences showed that the majority of substitutions had occurred at amino acid replacement sites indicating a rapid evolution of the IL-3 protein. After expression of a genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled large-scale production of the RhIL-3 polypeptide, RhIL-3 produced by Bacillus licheniformis and purified to homogeneity appeared to be approximately 100-fold more effective in stimulating Rhesus monkey hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed comparable stimulatory activity on normal as well as malignant human hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a unidirectional species specificity, which most likely restricts the in vivo effects of hIL-3 in Macaca species. PMID- 2257298 TI - Highly increased production of bone marrow-derived blood cells by administration of homologous interleukin-3 to rhesus monkeys. AB - Recombinant rhesus monkey interleukin-3 (IL-3) was administered to normal rhesus monkeys in graded doses ranging from 3 to 30 micrograms/kg/d subcutaneously for 30 consecutive days or given as a continuous intravenous infusion at a dose of 30 micrograms/kg/d for 16 days. After a lag phase of about 1 week, a highly increased, dose-dependent production of bone marrow-derived blood cells was observed, preceded by amplification of bone marrow hematopoietic progenitor cells. Simultaneously, peripheral blood progenitor cells rose. The increase included basophilic, eosinophilic and neutrophilic granulocytes, monocytes, and the erythrocyte and platelet lineages. Characteristically, a T-lymphocyte response was absent. It is concluded that IL-3 in vivo stimulates blood cell production from an immature, multipotent progenitor cell. PMID- 2257299 TI - Isolation and characterization of an acquired antithrombin antibody. AB - A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa). When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa Sepharose column. The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied. The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested. This IgG was also able to slightly prolong fibrinogen clotting by human IIa. Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II. Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration). The effect of the antibody on the reaction between IIa and AT III/heparin was investigated. Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody. These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested. However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity. These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy. The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect. PMID- 2257300 TI - Utilization of a continuous flow reactor to study the lipoprotein-associated coagulation inhibitor (LACI) that inhibits tissue factor. AB - A microperfusion system containing a glass capillary, the inner surface of which is coated with a phospholipid bilayer containing tissue factor, was used to explore the requirement for factors VIIa and Xa in the complex formed with the lipoprotein-associated coagulation inhibitor (LACI). Various combinations of factors VIIa, Xa, and LACI were perfused together or sequentially at a wall shear rate of 300 sec-1; a final perfusion of factors X and VIIa was performed to evaluate the residual tissue factor activity. Factor Xa concentration at the outlet of the tube was determined using a chromogenic substrate. In the presence of factors VIIa, Xa, and LACI, complete inhibition of tissue factor was observed on both phosphatidylcholine (neutral surfaces) and on phosphatidylserine/phosphatidylcholine (acidic) surfaces; omission of factors Xa or LACI resulted in no inhibition. The absence of factor VIIa in the initial perfusion steps resulted in no inhibition on neutral surfaces whereas about 90% inhibition was observed on acidic surfaces. Initial perfusion with factor Xa, but not LACI, followed by the remaining protein components, resulted in an inhibitory complex. Thus, it appears that a tissue factor:factor Xa:LACI complex can form in the absence of factor VIIa on acidic surfaces; moreover, our data imply a tissue factor binding site for factor Xa, but not for LACI. PMID- 2257301 TI - Monocytes enhance the bidirectional release of type I plasminogen activator inhibitor by endothelial cells. AB - Human umbilical vein endothelial cells cultured on a collagen lattice were used to study the effects of the interaction between human monocytes and endothelial cells on the production of type 1 plasminogen activator inhibitor (PAI-1) by endothelial cells. The effects of adherence and transendothelial migration of monocytes on endothelial PAI-1 release were compared with those of other leukocytes, conditioned media from monocytes, and interleukin-1 beta (IL-1 beta). Because the cell culture system used allows simultaneous analysis of the lumenal and the subendothelial compartment of endothelial cell monolayers, we also studied into which direction PAI-1 is released by endothelial cells. Under quiescent conditions, the net amount of PAI-1 accumulated at the lumenal side was twofold higher than that accumulated at the subendothelial side (about 2.0 micrograms PAI-1/10(6) cells and 1.1 microgram PAI-1/10(6) cells, respectively, in 24 hours), as analyzed by a quantitative immunoradiometric assay (IRMA). Direct cell-cell contact between highly purified monocytes and endothelial cells strongly enhanced the PAI-1 release by endothelial cells in a dose-dependent way, whereas lymphocytes and neutrophils did not affect endothelial PAI-1 production. The monocyte-mediated increase was first detected after 12 hours of incubation and lasted for at least 48 hours. In the presence of two monocytes per endothelial cell, the increases of PAI-1 at the lumenal side and at the subendothelial side were 87% and 32% in 24 hours, respectively. The effect of IL 1 beta on PAI-1 release by endothelial cells closely resembled that observed for monocytes. Monocyte-conditioned medium contained heat-labile product(s) which also, although to a much lesser extent than intact monocytes, enhanced endothelial PAI-1 release. Similarly, monocytes cultured on top endothelial cell separated by a microporous filter enhanced the release of PAI-1 to a lesser extent. Thus, these findings indicate that monocytes enhance endothelial PAI-1 release by mechanisms that are, at least in part, dependent on cell-cell contact. PMID- 2257303 TI - Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia. AB - A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa-specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a "private" platelet alloantigen that bears significance in rare instances of NAIT. PMID- 2257302 TI - Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly--- Val (GGC----GTC) mutation. AB - Fibrinogen Baltimore I is one of the very first congenital abnormal fibrinogens reported over several decades ago; however, the molecular defect of this dysfibrinogen has eluded identification. In fact, several reports misidentified the functional defect of Baltimore I, which has impaired fibrin monomer polymerization. Reversed-phase high-performance liquid chromatography analysis of lysyl endopeptidase digest of the purified Baltimore I gamma-chain showed an abnormal peptide not found in the co-existing normal gamma-chain of this heterozygote. Amino acid sequencing of this peptide indicated that gamma-chain Gly292 is replaced by valine. This observation was confirmed, and the genetic defect was determined by direct nucleotide sequencing of a polymerase chain reaction product containing codon gamma 292, which is mutated: GGC----GTC. The molecular defect of Fibrinogen Baltimore I lies in a region of the gamma-chain required for fibrin polymerization, suggesting that the integrity of gamma Gly292 is critical for fibrin assembly. PMID- 2257304 TI - Induction of interleukin-6 during human immunodeficiency virus infection. AB - Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, and other cell types, is induced by a variety of stimuli, including bacteria, viruses, and other cytokines. When normal monocyte cultures were exposed to a monocytotropic strain of human immunodeficiency virus (HIV), HTLV IIIBa-L, significant levels of IL-6 bioactivity were detected in the culture supernatants after 12 to 43 days of incubation, at a time when there was associated evidence of HIV production. Similarly, when normal monocyte cultures were cocultured with peripheral blood mononuclear cells from HIV-infected individuals, HIV replication in these cultures was associated with production of IL-6. In further studies, we determined that mean serum levels of IL-6 bioactivity were abnormally elevated in HIV-seropositive individuals with stage 1/2 infection (25.2 x/divided by 1.8 U/mL) and stage 3/4 infection (46.1 x/divided by 1.7 U/mL) when compared with normals (1.6 x/divided by 1.2 U/mL). In contrast mean serum IL-6 levels were not different from normal in stage 5/6 infection (2.7 x/divided by 1.6 U/mL). A selected group of 12 HIV-seropositive individuals (stages 1, 2, and 3) who harbored HIV capable of replicating in T cells but not in monocyte cultures had a mean serum IL-6 level of 5.3 U/mL (x/divided by 1.5), a value significantly lower (P less than .004) than that measured in control HIV-seropositive individuals infected with monocytropic HIV (39 x/divided by 1.9 U/mL). In addition, serum IL-6 levels in HIV-seropositive individuals (stages 1 through 6) correlated directly with serum immunoglobulin G (IgG) levels (R = .74, P less than .001). Monocytes but not T cells are capable of a high level IL-6 production in vitro, and monocyte-derived IL-6 stimulates Ig production in activated B cells. Thus, HIV-seropositive individuals who often are infected with monocytotropic HIV and often display abnormally elevated serum IgG levels may exhibit these abnormalities as a consequence of abnormally elevated IL 6 levels induced by HIV. PMID- 2257305 TI - In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. AB - The knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia (ALL) in general is limited. This is because of the lack of a suitable in vitro drug sensitivity assay, which is in part due to low in vitro ALL cell survival. We recently adapted the highly efficient 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to test cells from ALL patients and showed that its results were comparable with those of the DiSC assay, up to now the most valid but laborious assay. In this study, in vitro drug sensitivity was assessed in cells from 82 children with leukemia, 79 of whom had ALL, with the MTT assay. Dose response curves were obtained for 6 mercaptopurine, 6-thioguanine (6-TG), prednisolone (Pred), daunorubicin (DNR), vincristine (VCR), cytosine arabinoside (Ara-C), L-asparaginase (L-Asp), mafosfamide, and mustine. A cytotoxic effect of methotrexate could be detected in only a few cases. Large interindividual differences in drug sensitivity were detected. Compared with leukemia cells from newly diagnosed patients, leukemia cells from relapsed patients were significantly more in vitro resistant to 6-TG, Pred, Ara-C, mafosfamide and mustine but not to DNR, VCR, and L-Asp. Improvements of culture medium and methods to increase MTT reduction were studied. From 10 components tested, addition of insulin and bovine serum albumin to serum containing medium improved ALL cell survival. Addition of succinate did not increase the amount of MTT reduction. We conclude that the in vitro MTT assay highly facilitates large-scale studies on drug resistance of ALL patients that can lead to rational improvements in existing treatment protocols. PMID- 2257306 TI - Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy. AB - To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted. PMID- 2257307 TI - Platelet-derived neutrophil adherence-inhibiting factor in humans. AB - The effect of constituents of human platelets on leukocyte adherence was examined. Adherence-inhibiting factors (AIFs), which strongly inhibited neutrophil adherence to glass, were present in both cytosol and granule fractions of human platelets. On the Superose 6 gel chromatography (Pharmacia LKB Biotechnology, Uppsala, Sweden), the granular AIF was eluted as a single active peak (2,600 Kd), whereas cytosolic AIFs were eluted at two different positions (2,600 and 480 Kd). When platelets were stimulated by thrombin, granular AIF was released extracellularly without releasing a cytosolic marker. Using DE32 anion exchange chromatography and Superose 6 gel filtration, granular AIF was completely purified. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis suggests that granular AIF consists of two subunits with molecular masses of approximately 340 and 190 Kd. Purified granular AIF inhibited human neutrophil adherence to glass, plastic, and type IV collagen-coated plastic, whereas it did not affect monocyte adherence. These results suggest that granular AIF inhibits neutrophil adherence not only via nonspecific adsorption sites, but also via type IV collagen receptors. PMID- 2257308 TI - Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice. AB - The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02). PMID- 2257309 TI - A new method for isolation of reticulocytes: positive selection of human reticulocytes by immunomagnetic separation. AB - A method for isolating pure reticulocytes from leukocyte-depleted blood of normal persons is presented. The separation was achieved using an immunomagnetic technique. A monoclonal mouse antibody against human transferrin receptor was bound to magnetic beads conjugated with sheep antimouse antibody. The recovery of reticulocytes from peripheral blood was 15% to 42%. Blood used for isolation of reticulocytes could be stored for 4 days at 22 degrees C without altering the yield of reticulocytes. At 37 degrees C incubation, the reticulocytes matured rapidly and the transferrin receptor was found to have a half-life of 16 hours. The activity of several enzymes and the amount of creatine and hemoglobin A1C were measured both in the reticulocytes and peripheral blood. Of the enzymes, porphobilinogen deaminase had the best discriminatory power with a ratio of 8.8 between reticulocytes and peripheral red blood cells. The ratio for creatine was 16.7. The ability to isolate pure human reticulocytes, released after normal erythropoiesis, will offer new possibilities in the study of these cells. PMID- 2257311 TI - Treatment of DIC associated with APL. PMID- 2257310 TI - Combined syngeneic bone marrow transplantation and immunotherapy of a murine B cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin. AB - Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma. In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT. Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth. Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls. Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery. Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation. These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation. PMID- 2257313 TI - Malaria and the red blood cell. PMID- 2257312 TI - Some reflections concerning host erythrocyte-malarial parasite interrelationships. AB - During the intraerythrocytic development of the malarial parasite, the host cell's structure and function are altered to such an extent that the infected red blood cell may be regarded as a finely tuned, although imperfect, symbiotic organism. Problems such as the control of the parasite's life and cell cycles, volume regulation of the malaria-infected erythrocyte, the energy metabolism of the malaria-infected red blood cell, and the possible metabolic purpose for parasite oxidative stressing of its host cell, seem worth addressing at the outset. PMID- 2257314 TI - Biochemistry of red cell invasion. AB - We are still far from an explicit understanding of the events that characterize the invasion of red cells by malarial parasites at the structural and biochemical levels. The nature of the interaction between the attached parasite and the host cell; the origin of the parasitophorous vacuole; the identity, disposition, and arrangement of the propulsive proteins of the parasite; the functions of the rhoptry organelles; and the rearrangement of the host cell membrane to permit entry of the parasite remain to be elucidated. A hypothetical scheme is presented that pursues the processes involved in invasion from the biochemical events generated by attachment of the parasite, to the steric rearrangement of red cell membrane proteins, which culminates in invasion. PMID- 2257315 TI - The ultrastructure of red cell invasion in malaria infections: a review. AB - Within the circulation, the invasive stage of Plasmodium is the merozoite, a small elliptical cell. Electron microscopy shows that the merozoite can attach reversibly to erythrocytes by its adhesive coat, then form a close, irreversible contact by its apical end, triggering secretion from membranous vesicles (rhoptries and micronemes) on to the erythrocyte membrane. This causes the erythrocyte membrane to invaginate and the merozoite then becomes enclosed within a cavity lined by interiorized membrane. In uninfected erythrocytes, the surface membrane consists of a lipid bilayer in which lie various integral membrane proteins and glycoproteins, associated at their cytoplasmic ends with a network of other proteins constituting the membrane skeleton. There is much evidence that during invasion the membrane proteins and skeleton are removed from the invaginated membrane. There are also ultrastructural data suggesting that the rhoptries are able to generate membrane-like materials, which are inserted into the erythrocyte membrane to cause its inward expansion. Further expansion may be induced by the liberation of parasite secretions from another set of organelles (microspheres) released after the first stage of invasion. PMID- 2257316 TI - Preferential invasion of malarial merozoites into young red blood cells. AB - The preferential invasion of malarial merozoites into subpopulations of red blood cells (RBCs) in vivo and in vitro has been the subject of repeated discussions. In this paper, an attempt is made to summarize these discussions and to pinpoint the mechanism by which this preference could arise. The available data suggest that a relatively simple mechanism, related to the capability of the merozoite to rearrange the proteins of the cytoskeleton of the RBC may determine the invasion rate into mature versus very young RBCs (reticulocytes). There is no evidence for significant differences between mature RBCs and reticulocytes in the presence of membrane proteins which might play a role in receptor-ligand binding of merozoites to their host cell. Consequently, the concept of "reticulocyte preference" is left and the ability of penetrating both mature and immature RBCs, versus immature RBCs only, is given as an explanation for the presence of ringforms exclusively in reticulocytes as observed for several species of vivax type malaria parasites. The possible consequences of preferential invasion for the infection (in vivo) and the culture (in vitro) of different plasmodial species are discussed. PMID- 2257317 TI - Innate resistance to malaria: the intraerythrocytic cycle. AB - The human innate resistance to P. falciparum malaria is based on genetic features that affect several stages of the intraerythrocytic cycle of the plasmodia. HbS, HbE and alpha and beta thalassemia (in addition to G-6PD deficiency) are protective to the carriers, because they inhibit the intraerythrocytic growth period, and in the case of AS red cells, in addition, parasitosis make them detectable expeditiously by the spleen. Blood group polymorphisms can interfere with red cell invasion by plasmodia. HbC belongs to a special category, since it apparently interferes with the cycle at the moment of cell lysis and release of merozoites. Finally, ovalocytosis observed in South East Asia, which most likely corresponds to a cytoskeleton or membrane protein defect, protects from malaria by inhibiting invasion. It should be kept in mind that many of these red cell defects might protect individuals in the critical first 5 years of life by retarding the switch of HbF to adult hemoglobin, since the HbF containing red cells are less than hospitable to the parasite. PMID- 2257318 TI - Ultrastructure of malaria-infected erythrocytes. AB - Knobs, caveolae, caveola-vesicle complexes, cytoplasmic clefts, and electron dense material are five major ultrastructural changes found in the membrane skeleton and cytoplasm of erythrocytes infected with species of primate malaria. Knobs are electron-dense, conical evaginations of the erythrocyte surface, which are believed to mediate cytoadherence and sequestration of Plasmodium falciparum infected erythrocytes. Caveolae and caveola-vesicle complexes are flask-shaped invaginations of the membrane skeleton, which may be involved in the uptake or export of host- or parasite-derived substances. Cytoplasmic clefts are flattened or circular membranous structures found in the erythrocyte cytoplasm between the intracellular parasite and the host cell surface. The clefts are variable in length and bounded by two or more membranes. Fine, granular electron-dense material is often found on the cytoplasmic face of clefts or in amorphous packets in the erythrocyte cytoplasm. Immunocytochemistry has demonstrated that all of these ultrastructural changes are associated with the trafficking and interaction of specific malarial antigens with the host erythrocyte. PMID- 2257319 TI - Vesicle-mediated transport of membrane and proteins in malaria-infected erythrocytes. AB - Malaria parasites during intraerythrocytic development change the ultrastructure, biophysics, and the antigens of the host red blood cell membrane. Parasite encoded proteins are associated with, inserted into, or secreted across the infected erythrocyte membrane. Since parasites of the genus Plasmodium are eukaryotic cells, it must be assumed that they possess essentially eukaryotic modes of vesicle-mediated transport and translocation of proteins and membranes. Numerous studies have demonstrated vesicular structures in the cytoplasm of malaria-infected red blood cells and an assortment of parasite proteins associated with the different vesicles, membranes, and membrane-defined compartments. Some parasite polypeptides remain trapped between the parasite and the parasitophorous vacuole membranes PVM, whereas others are associated with morphologically distinct membrane-limited vesicles and vacuoles. Some of these same parasite protein antigens also associate with the erythrocyte membrane or with parasite-induced ultrastructural modifications in the membrane of the parasitized red blood cells. This implies that intracellular transport occurs in malaria-infected erythrocytes, a capacity that uninfected red blood cells normally lose upon enucleation. The specific locations of parasite antigens within the infected cell also implys the existence of targeting signals in the translocated parasite polypeptides and perhaps transport-mediating proteins. The genes corresponding to some of these translocated proteins have been sequenced. Typical (and in some cases atypical) signal peptide sequences occur, as well as a number of sequences that may result in posttranslational modifications. How or if these features figure in to the translocation across, and targeting to a particular membrane compartment of the intraerythrocytic parasite remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257320 TI - Hematopoiesis in human malaria. AB - This paper presents changes in the bone marrow of patients with malaria; it is based primarily on observations of bone marrows of 89 Gambian children with P. falciparum malaria and includes a review of the literature. Erythroid hyperplasia with dyserythropoiesis was found to be more common in patients with severe anemia and low grade parasitemia than in those with acute malaria. The dyserythropoietic changes are illustrated both with light photomicropraphs and with electron micrographs. The significance of the dyserythropoiesis and possible causes are discussed. Other changes in these patients with acute malaria include lymphocytosis in the bone marrow and reactive lymphocytes, monocytosis and mild neutrophilia in the peripheral blood. Giant metamyelocytes were also commonly seen in bone marrow of patients but were thought to be part of dysmyelopoiesis and not due to B12 or folate deficiency. Phagocytosis of erythrocytes, parasitized cells and nucleated cells was more commonly seen in macrophages in acute malaria, while phagocytosis of small particles such as merozoites was observed in neutrophils. Megakaryocytes were found to be increased in number in patients with acute malaria; a proportion of these cells had rounded nuclei, probably indicating accelerated platelet turnover. PMID- 2257321 TI - Properties of permeation pathways induced in the human red cell membrane by malaria parasites. AB - The intracellular development of malaria parasites in mature erythrocytes imposes on the host cell a major demand for supply of nutrients and disposal of waste products. So as to cope with these demands, the erythrocyte membrane undergoes profound alterations in its basic permeability properties. A few hours after being invaded by Plasmodium falciparum parasites, and before any structural changes are apparent on the surface, the molecular traffic across the red cell membrane changes both in intensity and in composition of permeating substances. The changes are of a gradual nature, developmentally related and dependent on de novo protein synthesis, but do not occur concurrently for all the classes of permeants. Molecules which permeate very poorly into uninfected cells, such as hexitols (e.g., sorbitol and myoinositol), amino acids (e.g., glutamine, threonine, and histidine), a variety of organic acids and metal ions show a marked increase in their permeation rates across the host cell membrane. Likewise, substances whose normal permeation pathways conform with those of facilitated diffusion (e.g., hexoses, nucleosides, choline, and some amino acids), gain access into the host cytosol either by modified or additional permeation pathways. It has been proposed that three major new pathways are induced in the membrane of infected cells: (1) one of pore-like properties, which can accommodate most of the water soluble permeants, including anionic substances; (2) a protein-lipid interface, which can accommodate compounds of relatively higher hydrophobic character; and (3) modified constitutive transporters or modified lipid surroundings with altered transport activities. The pores are blocked by permeant bioflavonoid glycosides whose sites of binding are endofacial, and amount to less than a thousand per cell. In addition to serving as specific targets for transport blockers, the new sites of permeation can also serve as routes for enhanced delivery of cytotoxic agents into parasitized cells. PMID- 2257322 TI - Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite. AB - Selected aspects of the metabolism of Plasmodium falciparum are reviewed, but conclusions based on the study of other species of plasmodia are intentionally not included since these may not be applicable. The parasites increase glucose consumption 50-100 fold as compared to uninfected red cells; most of the glucose is metabolized to lactic acid. The parasite contains a complete set of glycolytic enzymes. Some enzymes such a hexokinase, enolase and pyruvate kinase are vastly increased over corresponding levels in uninfected red cells. However, the pathway for synthesizing 2,3-diphosphoglycerate (2,3-DPG) is absent. Parasitized red cells show a decline in the concentration of 2,3-DPG which may function as an inhibitor for certain essential enzyme pathways. Pentose shunt activity is increased in absolute terms, but as a percent of total glucose consumption, there is a decrease during parasite infection of the red cell. The parasite contains a gene for G6PD and can produce a small quantity of parasite-encoded enzyme. It is not clear if the production of this enzyme can be up-regulated in G6PG deficient host red cells. The NADPH normally produced by the pentose shunt can be obtained from other parasite pathways (such as glutamate dehydrogenase). NADPH may subserve additional needs in the infected red cell such as driving diribonucleotide reductase activity--a rate limiting enzyme in DNA synthesis. The role of NADPH in protecting the parasite-red cell system against oxidative stress (via glutathione reduction) remains controversial. Parasitized red cells contain about 10 times more NAD(H) than uninfected red cells, but the NADP(H) content is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257323 TI - Purines and pyrimidines in malarial parasites. AB - In order for the plasmodium malarial parasite to replicate in the human erythrocyte it requires metabolic pathways which are not operative in the host erythrocyte. Thus, the malarial parasite not only synthesizes enzymes for purine salvage and interconversion, for the pyrimidine biosynthetic pathway de novo, and for the folate cycle, but it also alters the host erythrocyte membrane in respect to the transport of purines. Several of the plasmodium enzymes from these pathways have been cloned and these appear to be highly homologous to the corresponding human enzymes. However, enzymes which have been purified from Plasmodium, have demonstrated physicochemical and kinetic differences and may be potential targets for chemotherapy. Inhibition of individual enzymes, such as the dihydroorotate dehydrogenase (DHO-DHase), and inhibition of the inserted pathway from IMP to AMP and IMP to GMP hold considerable promise as chemotherapeutic targets. An entirely new approach in inhibiting malarial growth involves the altered nucleoside transporter in the infected cell membrane through which cytotoxic compounds may be selectively targeted into only the infected cell. PMID- 2257324 TI - Oxidative stress and the redox status of malaria-infected erythrocytes. AB - The chief focus of this article is the relationship between the redox status of the host erythrocyte and that of the malaria parasite. Roles for oxidative processes in the reduced growth of malaria parasites in abnormal erythrocytes, in the host response against the parasite, and in the action of certain anti malarial drugs are widely accepted as being established. We believe the evidence underpinning these ideas to be unacceptably deficient in a number of areas and suggest some ways in which the questions could be re-examined experimentally. PMID- 2257325 TI - Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes. AB - The asexual development of Plasmodium within the mature mammalian erythrocyte is associated with intense membrane biogenesis, notably to ensure the increase in the size of the parasite and of the parasitophorous vacuolar membranes PVM. A considerable increase in the content of most lipids except cholesterol [namely, phospholipids PL, neutral lipids, and fatty acids FA] occurs. The PL composition and the constitutive FAs of the parasite differ markedly from the original host cell membrane. Particularly notable is the absence of cholesterol and sphingomyelin SM from the parasite membranes. How can the parasite obtain such a quantity of new lipid molecules in a host cell totally devoid of any lipid biosynthetic activity? Like the normal erythrocyte, the infected cell is unable to synthesize cholesterol or FAs. In contrast, it exhibits an intense biosynthesis of neutral lipids and a bewildering variety of PL biosyntheses. Phosphatidylcholine PC is synthesized by a de novo pathway, and also by methylation of phosphatidylethanolamine PE, which itself originates from de novo biosynthesis or from decarboxylation of phosphatidylserine PS. Hence, interference with this intense and specific PL metabolism could provide the basis for a new malaria chemotherapy. Indeed, compounds that interfere with the entry of the plasmatic precursors (FAs or polar heads) or with their metabolism are lethal to the parasite. Lastly, we focus on the structural modifications of the host cell membrane with respect to lipids, including increased fluidity and enhanced transbilayer mobility of PLs. Possible modifications in the asymmetric distribution of PLs in the host cell membrane are discussed in light of the various methods used and their limits. The capacity of infected cells to take up and metabolize large quantities of exogenous vesicles of PLs accounts for the intense dynamics of lipids in the infected erythrocytes. PMID- 2257326 TI - Proteases in malaria-infected red blood cells. AB - The discrimination between erythrocyte and Plasmodium proteases is now made easier by using synthetic fluorogenic substrates, high-pressure liquid chromatography, reliable methods of cell preparation, as well as radiolabeled extracts from in vitro cultures of P. falciparum. The reinvasion process of an erythrocyte by a merozoite involves specific proteinases, which were recently identified using fluorogenic peptidyl-AEC substrates and by analysis of schizont and merozoite extracts with the gelatin-SDS-PAGE method. The biological targets of both host and parasite proteinases are not yet well characterized because Plasmodium-infected red blood cells contain at least four compartments with different pH values, which could modulate the proteinase activities according to their pH range activity. The processing of the precursor for the major merozoite surface antigens involves cleavage of very specific peptidic bonds by, so far unknown, proteinases. The depletion of the erythrocyte cytoskeleton could depend on a 37 kD proteinase, which cleaves spectrin and the 4.1 component, as shown in P. berghei and P. falciparum species. In contrast to leupeptin, which inhibits the merozoite release from schizont-infected erythrocytes, the structural inhibitor analogous to the Val-Leu-Gly-Lys (or Arg) P. falciparum neutral proteinase substrates appears to block the invasion step of erythrocytes by merozoites and may open new trends in chemotherapeutical strategies. PMID- 2257327 TI - Cytoadherence of malaria-infected erythrocytes. AB - Malaria-infected erythrocytes express new antigenic structures on their surface. Some of these molecules are responsible for the cytoadherence of infected cells to endothelial cells which, because of the sequestration produced, may, in turn, be responsible for the pathogenesis of the severe forms of the disease in humans (e.g., cerebral malaria). This paper critically reviews the state of the art concerning cytoadherence, with particular emphasis on the different experimental approaches that have been used to study the phenomenon and the parasite molecules that may be involved. PMID- 2257328 TI - Uptake of cadmium and nickel in banana prawn (Penaeus merguiensis de Man). PMID- 2257329 TI - Barium bioaccumulation in clams collected from different salinity regimens along the Saudi coast of the Arabian Gulf. PMID- 2257330 TI - Oxygen uptake of Pseudosuccinea columella and Fossaria cubensis treated with sublethal concentrations of CUTRINE-PLUS, an algicide. PMID- 2257331 TI - Sublethal effects of 2,2-dichloropropionic acid (dalapon) on Fossaria cubensis, intermediate host of the liver fluke, Fasciola hepatica. PMID- 2257333 TI - Fate of parathion in ground water in commercial cranberry culture in the New Jersey pinelands. PMID- 2257332 TI - Distribution and elimination of 14C-ethion in laying hens and eggs after oral exposure. PMID- 2257335 TI - Toxicity evaluation of the proposed secondary and the primary effluents discharged to Massachusetts Bay. PMID- 2257334 TI - Residues of organochlorine insecticides in fish from Mahala water reservoir, Jaipur, India. PMID- 2257336 TI - Growth dynamics of wheat (Triticum aestivum L.) exposed to sulfur dioxide pollution. PMID- 2257337 TI - Comparison of metal uptake between glutinous and non-glutinous rice for cadmium chloride, oxide and sulfide at the critical levels. PMID- 2257339 TI - Fetoplacental-maternal uptake of hexavalent chromium administered orally in rats and mice. PMID- 2257338 TI - Effects of biphenyl ethers on the hepatic mixed--function oxidase (MFO) systems and on the conversion of procarcinogens to mutagens. PMID- 2257340 TI - Effects of laboratory lighting on the stability of analytical grade pesticides. PMID- 2257341 TI - Refurbishment of nonwoven protective apparel fabrics contaminated with methyl parathion. PMID- 2257342 TI - Pesticide exposure of applicators working in tea plantations. PMID- 2257343 TI - Handgun applicator exposure to ethion in Florida citrus. PMID- 2257344 TI - Smoking habits of doctors and nurses and their attitudes towards smoking habits of patients. PMID- 2257345 TI - 200 million may die prematurely in the 1990s. PMID- 2257346 TI - World report on tropical diseases. PMID- 2257347 TI - American Lung Association President's Award. Presentation of the award to Dr. K. Styblo by Dr. A. Davis. PMID- 2257348 TI - IUATLD awards and prizes. PMID- 2257349 TI - Recent developments in molecular biology of mycobacteria. AB - Molecular biology is beginning to revolutionise the study of tuberculosis and other mycobacterial diseases. DNA hybridization is used to classify strains at the generic and specific level and, when combined with the polymerase chain reaction, may rapidly detect very small amounts of mycobacterial DNA in clinical material. Restriction endonuclease mapping or the more refined restriction length polymorphism analysis is used to type strains at the sub-specific level for epidemiological purposes. Detection of plasmids is also an epidemiological aid and there is considerable interest in the role of plasmids as determinants of pathogenicity and virulence of some mycobacterial species. Genomic libraries provide a source of DNA probes for use in hybridization and restriction length polymorphism analysis and pure antigens in large quantities for experimental and diagnostic use. Vectors for the insertion of genes into mycobacteria provide a way of analysing genes relevant to virulence and protective immunity and a means of producing new vaccines for use against leprosy as well as tuberculosis. Finally, the ability to clone mammalian genes in bacteria enables immunological mediators to be produced in quantity for the elucidation of immune mechanisms in mycobacterial infections and possibly for therapeutic use. PMID- 2257350 TI - A modern approach to the immunotherapy of tuberculosis. PMID- 2257351 TI - Old BCG replaced by new vaccine? Human leukocyte antigens (HLA) and mycobacterial disease. PMID- 2257352 TI - First experience with BCG discontinuation in Europe. Experience in Sweden 15 years after stopping general BCG vaccination at birth. PMID- 2257353 TI - First experience with BCG discontinuation in Europe. Project on discontinuation of BCG vaccination in newborns in Czechoslovakia. PMID- 2257355 TI - Epidemiology and surveillance of tuberculosis in the German Democratic Republic. PMID- 2257354 TI - First experience with BCG discontinuation in Europe. BCG vaccination and HIV infection. PMID- 2257356 TI - Epidemiological situation and surveillance of tuberculosis in England and Wales. PMID- 2257357 TI - Tuberculosis surveillance system in Japan. PMID- 2257358 TI - "Elimination": of tuberculosis or of tuberculosis control programs. PMID- 2257359 TI - The elimination of tuberculosis in The Netherlands. PMID- 2257360 TI - The application of the WHO standard tuberculin test in the elimination phase of tuberculosis. PMID- 2257361 TI - Organization of laboratory services in low prevalence countries, our personal view. PMID- 2257362 TI - Nucleic acid based methods for detection of mycobacteria. PMID- 2257363 TI - Methods of tuberculosis case-finding in The Netherlands. PMID- 2257364 TI - Infectiousness of tuberculosis. PMID- 2257365 TI - Case-finding in the elimination phase of tuberculosis: tuberculosis in displaced people. PMID- 2257366 TI - Case-finding in the elimination phase of tuberculosis: high risk groups in epidemiology and clinical practice. PMID- 2257367 TI - Opportunist mycobacteria. PMID- 2257369 TI - Chemoprophylaxis and chemotherapy of tuberculosis in HIV infected patients. PMID- 2257368 TI - The use of fixed-dose combinations in antituberculous chemotherapy. Rationale for their application in daily, intermittent and pediatric regimens. PMID- 2257370 TI - HIV infection and tuberculosis in the United States and in Europe. PMID- 2257371 TI - Present and new drug regimens in chemotherapy and chemoprophylaxis of tuberculosis. PMID- 2257372 TI - Maintenance of a tuberculosis programme in the elimination phase. PMID- 2257373 TI - WHO's role for tuberculosis control in the world. PMID- 2257374 TI - The IUATLD and its role. PMID- 2257375 TI - Housing and health: interrelationship and community impact. PMID- 2257376 TI - Housing and health. PMID- 2257377 TI - Origins of public health collapse in New York City: the dynamics of planned shrinkage, contagious urban decay and social disintegration. PMID- 2257378 TI - The new urban niche of homelessness: New York City in the late 1980s. PMID- 2257379 TI - Community organization, housing, and health: a perspective for public health workers. PMID- 2257381 TI - Quality of the residential environment, health, and well being. PMID- 2257380 TI - Housing conditions and the quality of children at birth. AB - Low birth weight (less than 2,501 grams at birth) rates were computed for the 338 health areas of New York City for three time periods: 1969-1971, 1979-1981, and 1985-19. Frequency distributions of the 338 health areas were developed according to the percent of babies with birth weights less than 2,501 grams for each of the periods indicated above. Comparison of the 1970 and 1980 distributions indicates a decrease in low birth weight rates, but an increase in both tails of the 1980 distribution, resulting in greater variability in 1980 rates. This polarization reveals that some areas of New York City had achieved very low rates while other areas had increased to exceptionally high rates. The distribution for 1986 (1985 1987) indicates a continuation of rate shifts, particularly in the low rate tail where, in comparison with 1980, 19 additional health area populations had rates of low birth weight less than 0.05. With 1970 as a reference point, 71 additional health area populations had achieved rates less than 0.05 by 1986. In contrast, the high tail for 1986 does not shift and is very similar to that of 1980. As previously noted, the shift in rate values in the high tail from 1970 to 1980 is not in the expected direction and contributes to the polarization of health status in New York City populations by contributions of newborns. Low birth weight values for 1986 stabilize this shift in the "wrong" direction. The range of minimum and maximum values, which increased from 0.144 to 0.190 to 0.226 for 1970, 1980, and 1986 respectively, document the change in degree of polarization. Health areas in the high low birth weight tail experienced the greatest amount of housing destruction and community devastation between 1970 and 1980. PMID- 2257382 TI - Health effects of environmental toxins in deficient housing. PMID- 2257383 TI - Health effects of housing status on children: a house is not a home. PMID- 2257384 TI - The impact of housing policies on community social disorganization and crime. PMID- 2257385 TI - Interaction of housing and health care institutions. PMID- 2257386 TI - Comprehensive city interventions. PMID- 2257388 TI - One city, one future. PMID- 2257387 TI - Nurturing grassroots initiatives for health and housing. AB - This article has discussed the need to support grassroots community development. Grassroots community development requires the development and maintenance of voluntary community organizations (e.g., block, neighborhood, and tenant associations). These organizations have proved effective in the social, physical, and economic development of a community. The challenge facing policy makers and strategists is to develop a system that supports a multitude of community initiatives. This article has discussed such an "enabling system" and structure, functions, and services required as part of this system. The challenge we face is to increase the problem-solving capacity of disenfranchised communities. One of the biggest barriers we face in this mission is the competition and lack of coordination among professional service organizations. PMID- 2257389 TI - Housing and health: conclusions and challenges for the future. PMID- 2257390 TI - Centralize cancer services. PMID- 2257391 TI - More DGH cancer consultants. PMID- 2257392 TI - Controlling hypertension: how far have we progressed? PMID- 2257393 TI - AIDS and paranoid hostility. PMID- 2257394 TI - Hidden victims of childhood sexual abuse. PMID- 2257395 TI - Exclusion diet for cyclical breast pain? PMID- 2257396 TI - Multidisciplinary functioning can and does work. PMID- 2257397 TI - Orthopaedic negligence: the tip of the iceberg? AB - Doctors seem helpless to stem the rising tide of negligence cases. This is partly because we practice in a generally more litigious society, but also because we only look superficially at negligence. We have traditionally looked only at the negligent act--in this paper the causes of such acts are explored. PMID- 2257398 TI - Missing the small print: problems with antibiotic therapy. PMID- 2257399 TI - Congenital intestinal atresia. AB - Surgery for infants with intestinal atresia has evolved along with the development of specialized neonatal surgical units. This once fatal condition now carries a better than 85% chance of survival and an excellent long-term prognosis. Recent advances in bowel preservation techniques have reduced morbidity and improved gut function in both the long and the short term. PMID- 2257400 TI - Intravaginal culture: present and potential uses. AB - Over recent years, a simplified method of in-vitro fertilization (IVF), known as intravaginal culture (IVC), has been developed. This article will outline the background to its introduction, provide technical details regarding its practice, review the results achieved to date and explore some of the areas in which this innovation may prove useful in the future. PMID- 2257401 TI - Disability medicine. AB - Rehabilitation/disability medicine has become big business in the USA, Europe and Scandinavia but has yet to establish firm footing as a specialty in the UK. Under the reforms of the Government's White Paper, however, time in hospital becomes money. The need for early re-integration and maintenance of patients in the community may well provide the cue for disability medicine to emerge as a specialty in its own right. But what is the nature of this specialty and who should do it? PMID- 2257402 TI - The causes and control of anxiety. AB - The 20th century has been described as the age of anxiety. Many have claimed that the pressures of a modern technological and competitive society are too great. Anxiety is a normal part of reaction to threats created by life situations especially when control is low. Some people perpetuate constant anxiety by oversensitivity to environmental events. Anxiety can reduce daily efficiency and become self-enhancing. Biological mechanisms may also sustain anxiety further. Treatments include addressing both the cognitive and the biological aspects of the state. Training people to cope with life and to find forms of control may be the most beneficial in the long term. PMID- 2257403 TI - How to control epistaxis. AB - Epistaxis is a common problem in medical practice. This article outlines the basic techniques used to control it. In severe cases, prompt management is essential and may save life. PMID- 2257404 TI - Psychological problems in adolescents from ethnic minorities. AB - This article reviews clinical and theoretical issues of particular importance in working with adolescents of black and white minority origin. This includes differences in definition of competence and stage-specific family tasks through the life cycle. A checklist covering basic points in an ethnocultural sensitive assessment is presented. It is argued that in order to be effective, therapeutic strategies need to mobilize strengths within an ethnocultural context. PMID- 2257405 TI - Transfer of the thermally injured patient. AB - Treatment of a patient with a severe thermal injury differs greatly from that of a victim of multiple trauma: if there have been no other injuries, the burned patient will be transferred as soon as possible to a regional burns unit. Our suggested protocol highlights the differences and their management. PMID- 2257406 TI - Selective parenteral and enteral antisepsis regimen (SPEAR). AB - With infection rates approaching 80% for patients staying in ICU for more than 5 days there is clearly a need for effective prophylaxis. SPEAR is a system of antimicrobial prophylaxis which extends the regimen of selective digestive tract decontamination to encompass systemic antimicrobial prophylaxis and includes oral non-absorbable antibacterial and antifungal agents with initial use of a broad spectrum systemic antibacterial. PMID- 2257407 TI - Managing people. AB - Doctors relate to a wide variety of people including patients and their relatives, medical colleagues and other health-care staff and health service managers. In order for these relationships to be effective, they need to possess a high level of people management skills. This paper identifies the nature of the key relationships and presents a model and description of the skills required. PMID- 2257408 TI - Inhaled foreign bodies in the adult as a cause of unresolved pneumonia. PMID- 2257409 TI - Clinical assessment, management and prognosis. PMID- 2257410 TI - Fighting spirit and breast cancer. PMID- 2257411 TI - Pneumocystis carinii pneumonia. PMID- 2257412 TI - Transport of the critically injured. PMID- 2257413 TI - Organisation of a microsurgical laboratory. PMID- 2257414 TI - The role of lymphocytes in wound healing. AB - In the past, lymphocytes have usually been associated with chronic inflammatory conditions and only recently have animal experiments indicated a possible role in wound healing. The present paper describes a study of lymphocytes in human wounds and scars using monoclonal antibody stains. The results suggest that T lymphocytes may play an important regulatory role in wound healing and scar formation. PMID- 2257415 TI - Q-switched ruby laser treatment of tattoos; a 9-year experience. AB - Nine years of clinical experience of the application of the Q-switched ruby laser to the removal of tattoos is presented. This laser achieves optimal removal of blue/black amateur tattoos by its selective interaction with the dermal suspensions of pigment which constitute the tattoos. The scar free cosmesis thus achieved is a considerable improvement on non-specific laser techniques whereby the laser is absorbed to a comparable degree in both pigmented and non-pigmented tissue. Long-term results are analysed and it is noted that a variety of professional tattoos may also respond to treatment. The mechanisms and appearance are discussed and correlated with short-term healing processes. It is found that power densities in the range 1200-2800 GW/m2 are most suitable. Appropriate dosimetry can be witnessed by the appearance of opaque intradermal vacuoles corresponding to the vaporization of the tissue water surrounding the pigment suspensions. Treatment by Q-switched ruby laser offers a viable scar-free option for a wide range of dark tattoos, leading to a more acceptable clinical outcome in most cases than other current therapies. PMID- 2257416 TI - The cranio-facio-cervical scoliosis complex. AB - Six patients are presented with facial asymmetry including vertical orbital dystopia in association with torticollis. All six have also had other abnormalities. Some degree of hemifacial microsomia was present in five of the six, a so-called plagiocephalic or rhomboid skull with normal cranial sutures in four of the six, and cervical spine anomalies in four of the six. Other deformities have also been noted. The condition is best named the cranio-facio cervical scoliosis complex. The implications for treatment of the facial asymmetry, in particular the unequal levels of the orbits in the established deformity, are discussed and a surgical plan which has been used in four patients described. PMID- 2257418 TI - Imaging the plantaris tendon with ultrasound. AB - A quick, non-invasive method of imaging plantaris using real-time ultrasound is described. Preoperative scanning of patients who may require the use of plantaris as a tendon graft will identify those with congenital absence of plantaris and so avoid an unnecessary surgical exploration. PMID- 2257417 TI - The effects of very early palatal repair on speech. AB - One hundred subjects were evaluated to investigate speech intelligibility at age 5 following very early palate repair. Evaluation was achieved using a visual analogue. The effect of articulation, nasal resonance and nasal escape on intelligibility, and other factors which may affect results, such as fistulae, otitis media, cleft types and age of repair, are discussed. Results show that 87 subjects had acceptable speech and 13 had unacceptable speech. Nine subjects had poor articulation, 9 had moderate to severe nasal escape and 7 had moderate to severe nasal resonance. Only 6 subjects required pharyngoplasty. PMID- 2257419 TI - Joint orthopaedic and plastic surgery management of types III and IV lower limb injuries. AB - A questionnaire survey of orthopaedic registrars regarding the management of severe lower limb injuries were performed with particular emphasis on the role that co-operation with plastic surgeons might play in the management of these injuries. It was clear that both specialties have similar views. The importance of this co-operation is discussed. PMID- 2257420 TI - The island sensate ulnar artery flap for reconstruction around the elbow. AB - Elbow joint prostheses have now become reliable and provide stable movement. Some do have rather sharp edges on the ulnar component which, particularly in the rheumatoid arthritics and the elderly, may erode the skin, leading to exposure. Various flaps will provide cover to this area but do tend to re-ulcerate, probably due to inability to appreciate excess pressure. The ulnar artery flap, including the medial cutaneous nerve of the forearm, provides durable and sensitive cover, preventing re-exposure. Its successful use in two cases is described. PMID- 2257421 TI - Chromic acid burns; beware, be aggressive, be watchful. AB - Two cases involving the development of systemic toxicity and prolonged wound healing in small percentage area burns to chromic acid are reported. The treatment of chromic acid burns is reviewed and a protocol of management suggested. PMID- 2257422 TI - The amniotic band syndrome: single-stage correction. AB - Two cases of amniotic band syndrome treated by single-stage excision of the ring and multiple Z-plasty repair are presented. In both cases the author found the procedure technically easy and clinically safe. No complications were encountered in either case. PMID- 2257423 TI - The extended free scapular flap. AB - The free scapular flap, supplied by a single circumflex scapular vascular pedicle, can be safely extended beyond the midline of the back. The upper back can be a donor for very large and long flaps, ideal for resurfacing large defects. PMID- 2257424 TI - From Moses to Mahon (Gillies Memorial lecture 1989). PMID- 2257425 TI - Digits in the mouth; a peculiar chapter in cleft lip and palate surgery. AB - In 1901 von Eiselsberg reported closing a fistula of the hard palate using the patient's little finger. The case is reviewed here and set in the context of its time. PMID- 2257426 TI - Reconstruction of Achilles tendon using vascularised fascia lata with free lateral thigh flap. AB - A case of Achilles tendon reconstruction using free vascularised fascia lata joined to a lateral thigh flap is reported. This is a simple one-stage reconstruction and a sufficiently strong tendon can be obtained. PMID- 2257427 TI - "Conchal show" measurements: a new idea in prominent ear correction. AB - The average "conchal show" has been determined in a series of patients and a device is described to measure conchal show in prominent ears. By measuring the conchal show preoperatively, the surgeon can determine exactly how much to reduce the concha. PMID- 2257428 TI - Plastic surgery outpatient audit: principles and practice of "consultant only" clinics. AB - The effect of instituting "consultant only" clinics on plastic surgery outpatient activity was to produce a 19% reduction in both clinic sessions and new patient bookings, but a 50% reduction in booked follow-up patients; non-attender rates reduced from 20% to 11% (Northern General Hospital, April 1986-March 1989). Mean clinic attendances reduced from 35 to 26 (Northern General Hospital) and from 33 to 27 (Barnsley District Hospital)--26% and 18%, respectively. Analysis of new referrals to such clinics in the 6 months January-June 1989 showed 41% of patients came from general practitioners, although 80% of "aesthetic" conditions came from this source. 31% of referrals were for malignancy, 51/72 (70%) being basal cell carcinomas. Malignancies waited on average 4 weeks, benign conditions 15 weeks, and "aesthetic" conditions 28 weeks from referral to consultation. Such clinic management has dramatically reduced follow-up episodes, but regulation of new patient attendances is associated with appreciable waiting times for non malignant conditions. To reduce such waiting times and pursue a "consultant only" clinic policy nationally requires many more consultants. PMID- 2257429 TI - Aluminium foil for three-dimensional defects. PMID- 2257430 TI - A distally based first web flap in the foot. PMID- 2257431 TI - Inhibition by L-glutamine of the release of endothelium-derived relaxing factor from cultured endothelial cells. AB - L-Glutamine (0.02-2 mM) but not D-glutamine (0.2 mM and 2 mM) inhibited the release of endothelium-derived relaxing factor (EDRF) from bovine aortic endothelial cells cultured in the presence or absence of L-arginine. Inhibition was maximal at a concentration of 200 microns, and was reversed by L-arginine (50 microns) but not D-arginine (100 microns). L-Glutamic acid (2 mM) or ammonium chloride (1 mM), putative products of the metabolism of L-glutamine in endothelial cells, had no effect on EDRF release. L-Glutamine (0.2 mM and 2 mM) but not D-glutamine (2 mM), L-glutamic acid (2 mM) or ammonium chloride (1 mM) also inhibited the generation of L-arginine in endothelial cells. Thus, L glutamine inhibits EDRF release by preventing the generation of L-arginine. PMID- 2257432 TI - The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa. AB - 1. The effects of neuropeptide Y (NPY) and a range of C terminal fragments were investigated both on basal short circuit current (s.c.c.) and electrical field stimulated responses in voltage clamped preparations in rat jejunal mucosa. 2. Most of the NPY fragments tested had direct effects upon the mucosa, reducing baseline s.c.c. with EC50 values of 1 micron or more. NPY was 30 times more effective than any of the fragments tested and the order of potency was: NPY much greater than NPY (11-36) greater than or equal to (12-36) greater than or equal to (13-36) greater than or equal to (14-36). NPY (15-36), (16-36), (20-36) and (22-36) were still less effective and complete concentration-response curves could not be constructed. NPY (26-36), des amido NPY and the C-terminal flanking peptide of NPY (CPON) were all inactive and did not significantly alter responses to NPY. 3. Electrical field stimulation (EFS) of mucosal preparations elicited rapid transient secretory responses in the presence of hexamethonium and atropine. NPY and fragments attenuated these secretory responses and where concentration-response relationships could be compared at a given time point the following order of potency was obtained: NPY much greater than NPY (11-36) greater than NPY (13-36). Again NPY (26-36), des amido NPY and CPON were ineffective, while at single concentrations (300 nM) a graded attenuation of EFS responses was obtained with NPY (14-36) greater than or equal to NPY (15-36) greater than NPY (16-36) greater than or equal to NPY (20-36) greater than NPY (22-36). 4. The attenuation of EFS responses by these peptides was not dependent upon the basal secretory state. Pretreatment of tissues with piroxicam reduced s.c.c. and attenuated further reductions in s.c.c. by NPY, but had no effect upon NPY-mediated inhibition of electrically-stimulated secretory responses. 5. NPY fragments attenuated both basal and EFS generated secretion. Since fragments are effective these receptors must, by definition be Y2-like. NPY (11-36) and NPY (13 36) at 300nm and 1 microM did not significantly attenuate secretory responses to either carbachol (CCh) or substance P (SP). A 1 microM concentration of either fragment was equivalent in effect to 30nm NPY upon basal current, but NPY at this concentration significantly reduced both CCh- and SP-induced secretion. The reduced spectrum of fragment activity together with the different order and potency ratios obtained with these three peptides indicates a presynaptic action for NPY and the fragments. PMID- 2257433 TI - Inhibition of human platelet activation by polymorphonuclear leukocytes. AB - 1. The effect of unstimulated human polymorphonuclear leukocytes (PMNs) on platelet activation was examined. 2. Human platelet aggregation and adenosine 5' triphosphate (ATP) release induced by collagen (1-2 micrograms ml-1); thrombin (0.01-0.02 u ml-1) or arachidonic acid (AA) (0.1-0.2 mM) were markedly inhibited when conducted in the presence of unstimulated PMNs. 3. Platelet inhibition induced by PMNs was dependent on the number of PMNs and on the incubation time of the mixed cell suspension. 4. Platelet inhibition was not reversed in time when PMNs were depleted from the mixed-cell suspension. 5. PMN-mediated platelet inhibition was not mediated by AA metabolites, oxygen reactive intermediates, nitric oxide or proteases. 6. The factor(s) accounting for the platelet inhibition mediated by PMNs are not yet characterized. PMID- 2257434 TI - Role of epithelium in agonist-induced contractile responses of guinea-pig trachealis: influence of the surface through which drug enters the tissue. AB - 1. A method has been used in guinea-pig isolated tracheal rings to achieve selective drug entry from the adventitial or mucosal surface. A study has been made of the effects of epithelium removal on responses to spasmogens entering the tissue solely from the adventitial or the mucosal surface. 2. Cumulative concentration-response curves for KCl (1 to 100 mM), acetylcholine (0.1 microM to 10 mM) and histamine (1 microM to 1 mM) were constructed in intact and epithelium denuded tracheal rings in circumstances where drug entry was unrestricted or restricted to the adventitial or mucosal surface. 3. Epithelium removal did not alter the responsiveness or sensitivity of tracheal rings to KCl either when drug entry was unrestricted or when drug entry was restricted to the adventitial or mucosal surface. 4. When acetylcholine entered from the mucosal or adventitial surfaces of intact tracheal rings its concentration-response curve was displaced to the right with respect to that obtained for unrestricted drug entry. A greater rightward shift was observed for mucosal drug entry than for adventitial drug entry. Epithelium removal potentiated acetylcholine entering from the mucosal surface to a greater extent (27.5 fold) than it potentiated acetylcholine entering from both surfaces (4 fold). Epithelium removal did not potentiate effects of acetylcholine entering from the adventitial surface alone. 5. In intact tracheal segments, concentration-response curves for histamine entering from the mucosal surface were displaced to the right compared with those for histamine entering in an unrestricted fashion or from the adventitial surface alone. This displacement was absent in epithelium-denuded preparations. Epithelium removal potentiated (2-3 fold) histamine entering from the mucosal surface or entering in an unrestricted way. It did not potentiate histamine entering from the adventitial surface alone. 6. Our findings suggest that the epithelium does not modulate tracheal responses to KC1. Its ability to modulate responses to acetylcholine and histamine is observed when these spasmogens enter the tissue from the mucosal surface but not when they enter from the adventitial surface. The mechanism by which epithelium removal preferentially potentiates acetylcholine and histamine entering from the mucosal rather than the adventitial surface remains to be determined. PMID- 2257435 TI - Effects of diltiazem on calcium concentrations in the cytosol and on force of contractions in porcine coronary arterial strips. AB - 1. Using front-surface fluorometry with fura-2-loaded porcine coronary arterial strips, we simultaneously measured effects of a Ca2+ antagonist, diltiazem, on cytosolic Ca2+ concentrations [( Ca2+]i) and on tension development. 2. In the presence of extracellular Ca2+ (1.25 mM), histamine concentration-dependently induced abrupt (the first component) and then sustained (the second component) elevations of [Ca2+]i. In the absence of extracellular Ca2+, histamine induced transient elevations of [Ca2+]i, and the time course was similar to that of the first component observed in the presence of extracellular Ca2+. Histamine caused a greater contraction for a given change in [Ca2+]i than did potassium, at [Ca2+]i over 300 nM. 3. Diltiazem, 10(-8)M to 10(-5)M, concentration-dependently inhibited the second component of [Ca2+]i elevation and tension development induced by histamine (10(-5) M). Only at higher concentrations (over 10(-5) M) did diltiazem inhibit the first component of increases in [Ca2+]i and tension development induced by histamine, both in the presence and absence of extracellular Ca2+. 4. Diltiazem (10(-6) M) inhibited increases in [Ca2+]i and tension development induced by cumulative applications of extracellular Ca2+ during K(+)-depolarization. The curve of [Ca2+]i against tension of these Ca2(+) induced contractions obtained in diltiazem-treated strips overlapped with that obtained in untreated strips. This suggests that diltiazem has no direct effects on contractile elements. 5. In contrast, the histamine-induced Ca2(+)-tension curve (second component) was shifted in parallel to the left by diltiazem. 6. We conclude that diltiazem, at therapeutic concentrations, specifically inhibits extracellular Ca2+- dependent increases in [Ca2 +]i, with no effects on the release of Ca2 + from intracellular store sites or on Ca2 +-sensitivity of the contractile elements involved in the contractions induced by elevations of [Ca2 +]i. PMID- 2257436 TI - Zacopride and BRL 24924 induce an increase in EEG-energy in rats. AB - 1. The substituted benzamides, zacopride and BRL 24924 induced dose-dependent increases of the total EEG-energy of rats when applied intracerebroventricularly (i.c.v.) with ED50 values of 8.0 +/- 0.6 and 3.6 +/- 0.9 micrograms, respectively. Not only the energy of the low frequency hippocampal theta rhythm but also that of the other frequency bands was increased. 2. In contrast to i.c.v. application intraperitoneal administration of zacopride or BRL 24924 (1 and 10 mg kg-1) did not lead to an increase in EEG-energy. 3. The increase in EEG energy induced by zacopride (10 micrograms, i.c.v.) was blocked by ICS 205-930 (1 microgram, i.c.v.). Neither the 5-HT3 receptor agonist 2-methyl-5 hydroxytryptamine (30 micrograms, i.c.v.) nor the selective 5-HT3 receptor antagonist MDL 72222 (30 micrograms, i.c.v.) had any effect upon rat EEG. 4. Scopolamine (0.01 micrograms and 0.1 micrograms, i.c.v.) dose-dependently antagonized the effect of zacopride (10 micrograms, i.c.v.). 5. An agonist action of zacopride and BRL 24924 and inhibition of these effects by ICS 205-930 but not by MDL 72222 was recently described in isolated colliculi neurones from neonatal mice. The receptor involved was described as '5-HT4'. The present results indicate that the central effects of zacopride and BRL 24924 may be due to activation of such a 5-HT receptor. PMID- 2257437 TI - High- and low-affinity binding sites for [3H]-alpha, beta-methylene ATP in rat urinary bladder membranes. AB - 1. The characteristics of [3H]-alpha, beta-methylene adenosine 5'triphosphate ([3H]-alpha, beta-MeATP) binding to membrane preparations of rat urinary bladder detrusor were studied. 2. The rat bladder membrane preparation was obtained by multiple centrifugation. [3H]-quinuclidinyl benzilate [( 3H]-QNB) binding to this preparation demonstrated that the muscarinic receptor density was 4.32 times higher than that in the homogenate. [3H]-alpha, beta-MeATP binding was increased 3.88 times. 3. Saturation analysis revealed that the rat bladder membrane contained a high density of [3H]-alpha, beta-MeATP binding sites, which could be divided into a high-affinity component (Kd = 8.1-8.9 nM) and a low-affinity component (Kd = 67.0-119.8 nM). 4. Magnesium ions inhibited the maximum binding in a concentration-dependent manner. The maximum high-affinity binding was reduced from 10.32 pmol mg-1 protein in magnesium-free buffer to 4.62 pmol mg-1 protein with 25 mM MgCl2, while the maximum low-affinity binding was reduced from 58.84 pmol mg-1 protein to 14.24 pmol mg-1 protein. Kd values were not greatly affected. 5. The binding was a rapid reversible process. The association rate constants were 7.64 x 10(7) M-1 min-1 for high-affinity binding, and 7.31 x 10(6) M-1 min-1 for low-affinity binding. The dissociation rate constants were 0.2896 min-1 for high-affinity binding, and 0.6348 min-1 for the low-affinity binding. 6. Displacement experiments with unlabelled purinoceptor ligands confirmed that [3H]-alpha, beta-MeATP mainly binds to P2X-purinoceptors. The potency order was: a,/i-methylene ATP > fy-methylene ATP > suramin > ATP > ADP > 2-methylthio ATP > adenosine. 7. The results indicate that [3H]-a,,B-MeATP is a radioligand for the P2x-purinoceptor, which satisfies the basic criteria for use in radioligand binding assay. PMID- 2257438 TI - Binding of [125I]-endothelin-1 to rat cerebellar homogenates and its interactions with some analogues. AB - 1. [125I]-endothelin-1, over the concentration range 6 pM-10 nM, bound to a single site in homogenates of rat cerebellum with high affinity (Kd = 2.8 +/- 0.6 x 10(-10) M). The site was present in a concentration of 321 +/- 58 fmol mg-1 protein. 2. The rates of association and dissociation of [125I]-endothelin-1 with the binding site were slow (at 25 degrees C, k+1 = 8.0 +/- 1.3 x 10(5) M-1s-1; k 1 = 2.6 x 10(-4)s-1) and, on addition of a maximally displacing concentration of endothelin-1 (100 nM), 94.0 +/- 8.4% of the [125I]-endothelin-1 was still bound after 14 h. 3. [125I]-endothelin-1 binding was inhibited by a number of naturally occurring or genetically encoded members of the endothelin/sarafotoxin family of peptides. The order of potency was endothelin-3 = sarafotoxin S6b greater than endothelin-2 = endothelin-1 much greater than porcine proendothelin1-39. 4. Binding was also inhibited by analogues in which either one or both of the cystine disulphide bridges had been replaced by substitution with 2 or 4 alanine residues. The tetra-alanyl substituted analogue, [Ala1,3,11,15]endothelin-1, was equipotent with endothelin-1 at inhibiting the binding of [125I]-endothelin-1. [Ala3,11]endothelin-1 and [Ala1,15]endothelin-1, analogues which each contained one of the disulphide bridges from the parent peptide, were respectively 3 and 14 times less potent than the parent peptide. An analogue in which the Glu10 residue had been anisylated was 25 fold less potent than endothelin-1. 5. It is concluded that the structural requirements for binding to the cerebellar sites for [1251]_ endothelin-1 do not require the presence of the disulphide bridges characteristic of the endothelin/ sarafotoxin family. Rather, the binding may be more sensitive to the presence of bulky side chain substituents, at least in the smaller intramolecular loop. PMID- 2257439 TI - Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle. AB - 1. We previously isolated an extract from porcine left ventricle that possessed digitalis-like properties such as inhibition of cardiac and kidney Na+, K(+) ATPase, displacement of [3H]-ouabain from its binding sites and cross reactivity with digoxin antibodies. The extract also had a positive inotropic effect on the guinea-pig heart. 2. In the present study the positive inotropic response of the extract was characterized in canine right ventricular trabeculae. Maximum inotropic response (501 +/- 20%) was produced by 300 microliters and the half maximal increase occurred with 125 microliters of the extract. 3. Ouabagenin produced aftercontractions in rapidly paced trabeculae. Equipotent and even greater amounts of the extract did not produce aftercontractions. 4. The extract increased the amplitude of the delayed component (P2) of biphasic contractions produced by replacing about 92-96% of the external Ca with Sr. A smaller increase in the size of the early component (P1) was also seen. 5. The extract decreased post-rest potentiation after rest for 30s and 2 min. After 8 min of rest, post rest potentiation was converted to post-rest depression. 6. The extract (20 microliters) produced a decrease in the amplitude of the post-rest rapid cooling contracture (RCC) at all rest intervals. The steady state RCC, although greater than that in the control muscle, was increased to a lesser extent than the size of the steady state electrically driven contractions. 7. It is suggested that the extract from porcine left ventricle produces a positive inotropic response by increasing the trans-sarcolemmal influx of Ca. It also has additional effect(s) on the sarcoplasmic reticulum in that it may facilitate the loss of Ca from the sarcoplasmic reticulum and/or inhibit the uptake of Ca by the organelle. PMID- 2257440 TI - The effects of ryanodine and caffeine on Ca-activated current in guinea-pig ventricular myocytes. AB - 1. Action potentials from guinea-pig single ventricular myocytes were interrupted by application of a 300 ms voltage clamp to -40 mV in order to evoke the Ca activated tail current which is thought to be carried by Na:Ca exchange. Stimulation frequency was 1 Hz and temperature 36 degrees C. 2. The actions of ryanodine (1 microM and 10 microM) and caffeine (1 mM and 10 mM) on Ca-activated tail currents were investigated. 3. Exposure to 10 mM caffeine and ryanodine reduced tail currents associated with very abbreviated (12 ms duration) action potentials and greatly reduced the difference between first and steady-state tail currents at this action potential duration. These observations were interpreted in terms of suppression of Ca release from the sarcoplasmic reticulum (SR) stores. 4. Tail current decay during the voltage clamp is thought to reflect the fall in [Ca]i which accompanies muscle relaxation. Current decay is dependent on Ca extrusion via Na:Ca exchange and on Ca accumulation by the SR stores. Time constants of tail current decay were seen to decrease with increasing action potential duration. This relationship was not affected by 1 mM caffeine or 1 microM ryanodine. Ryanodine at 10 microM and 10 mM caffeine abolished this relationship and increased the time constants of current decay. An increase in the time constant of tail current decay was thought to reflect a reduction in the rate of Ca accumulation by the sarcoplasmic reticulum. 5. The actions of caffeine and ryanodine on the Ca-activated tail currents are consistent with a dose dependent leakage of Ca from the SR Ca stores. The Ca-activated tail current appears to be a useful tool in the study of Ca homeostasis. PMID- 2257441 TI - Influence of N-ethylmaleimide on action potential and force of contraction of guinea-pig papillary muscles. AB - 1. Standard microelectrode techniques were used to investigate the influence of N ethylmaleimide on the action potential, slow response action potential and force of contraction of guinea-pig papillary muscles. 2. N-ethylmaleimide, 3 x 10(-5) to 10(-4) mol l-1, concentration-dependently increased the force of contraction. The positive inotropic effect developed quickly and, with the largest drug concentration, was followed by a progressive decline of the contractile force. The action potential duration was progressively shortened by N-ethylmaleimide. 3. The effects of N-ethylmaleimide were not prevented in the presence of tetrodotoxin 3 x 10(-8) mol l-1 and propranolol 4 x 10(-6) mol l-1 or by a reduction of the Na(+)-concentration to 70 mmol l-1. 4. Verapamil, 10(-6) mol l 1, reduced the positive inotropic, but not the action potential shortening effect of N-ethylmaleimide. 5. In K(+)-depolarized muscles in the presence of propranolol and tetrodotoxin, N-ethylmaleimide 10(-4) mol l-1 increased the maximum depolarization velocity and the duration of the slow response action potential. The latter effect was transient and was followed by a progressive reduction of the action potential duration. 6. The most likely explanation for the action potential shortening effect of N-ethylmaleimide seems to be an increase of an outward potassium current while the transient inotropic effect of the drug may be caused, at least in part, by an increase of the slow inward calcium current. PMID- 2257442 TI - Kinins and peritoneal exudates induced by carrageenin and zymosan in rats. AB - 1. Kinins were measured by a radioimmunoassay in the inflammatory exudates induced by carrageenin or zymosan in the peritoneal cavity of normal Wistar rats and of kininogen-deficient Brown Norway rats. 2. After administration of carrageenin to normal rats, levels of immunoreactive kinins showed a single peak during the first two hours and then decreased. The presence of kinins preceded and accompanied the exudation of 125I-labelled albumin. Kinins were identified as bradykinin by chromatography. 3. Captopril, an inhibitor of kininase 2, increased the level of kinins and the volume of the exudates after carrageenin treatment. In Brown Norway rats, the volume of the exudates was small and contained little or undetectable amounts of immunoreactive kinins. 4. During zymosan-induced peritonitis, the exudates were devoid of immunoreactive kinins in both species. The volume of the exudates was larger in kininogen-deficient rats than in normal rats. 5. We conclude that in rats, the kinin system is a major factor responsible for the development of the inflammatory reactions induced by carrageenin, but is not involved in the reactions induced by zymosan. PMID- 2257443 TI - Impairment of relaxations to acetylcholine and nitric oxide by a phorbol ester in rat isolated aorta. AB - 1. This study compared the abilities of acetylcholine (ACh) (endothelium dependent) and nitric oxide (NO) (endothelium-independent and which may be the active component of the endothelium-derived relaxing factor) to relax rat isolated aortic rings contracted with equi-effective concentrations of noradrenaline (NA) or phorbol 12-myristate 13-acetate (PMA). 2. ACh and NO induced concentration-dependent relaxations of aortic rings contracted with NA (EC70 value: 0.2 microM). However, relaxations to both ACh and NO were markedly reduced in rings contracted with PMA (EC80 value: 0.5 microM). NO-induced relaxations of tissues were not affected by removal of the endothelium, but ACh induced relaxations were confirmed to be endothelium-dependent. 3. ACh (10 microM) induced a 10 fold increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels above control values in aortic rings contracted with NA (0.2 microM), but did not affect cyclic GMP levels in rings contracted with PMA (0.5 microM). 4. NO (3 microM) induced a 100 fold increase in cyclic GMP levels above control values in aortic rings contracted with NA (0.2 microM), but only an 11 fold increase in tissues contracted with PMA (0.5 microM). 5. It is concluded that the action (s) of EDRF (NO) are impaired in the presence of PMA by a mechanism that may involve the stimulation of protein kinase C in vascular smooth muscle cells. PMID- 2257444 TI - The inhibitory adenosine receptor at the neuromuscular junction and hippocampus of the rat: antagonism by 1,3,8-substituted xanthines. AB - 1. The ability of 1,3,8-substituted xanthines to antagonize the inhibitory effects of adenosine receptor agonist on the amplitude of nerve-evoked twitches of the rat phrenic-diaphragm and on the amplitude of orthodromically-evoked population spikes, recorded from the CA1 pyramidal cells of rat hippocampal slices, was investigated. 2. 1,3-Dipropyl-8-cyclopenthylxanthine (DPCPX), 1,3 dipropyl-8-(carboxymethyloxyphenyl)xanthine (XCC), 1,3-dipropyl-8-(4-[2 aminoethyl)amino)carbonylmethyloxyphenyl)x ant hine (XAC), 1,3-dipropyl-8-(2 amino-4-chlorophenyl)xanthine (PACPX), 8-phenyltheophylline (8-PT), 1,3-diethyl-8 phenylxanthine (DPX) and PD 115,199, in concentrations virtually devoid of effect on neuromuscular transmission, shifted to the right in a near parallel manner the log concentration-response curve for the inhibitory effect of 2-chloroadenosine (CADO) on nerve-evoked twitches of the phrenic-diaphragm. Linear Schild plots with slopes near to unity were obtained for all the xanthines. 3. The order of potency of the xanthines as antagonists of the effect of CADO in the phrenic diaphragm was DPCPX (Ki = 0.54 nM) greater than XCC (Ki = 10 nM), XAC (Ki = 11 nM), PACPX (Ki = 13 nM) greater than DPX (Ki = 22 nM), 8-PT (Ki = 25 nM) greater than PD 115,199 (Ki = 57 nM). The potency of DPCPX in antagonizing the inhibitory effects of R-N6-phenylisopropyladenosine (R-PIA) and 5'-N-ethylcarboxamide adenosine (NECA) on nerve-evoked twitch response was not statistically different from its potency in antagonizing the inhibitory effect on CADO. 4. In the hippocampal slices, DPCPX, XCC and XAC, used in concentrations virtually devoid of effect on population spike amplitude, shifted to the right in a near parallel manner the log concentrationresponse curve for the inhibitory effect of CADO on the amplitude of the population spikes. The Schild plots were linear with slopes near unity. 5. The potencies of DPCPX (K, = 0.45 nM) and XAC (K, = 11 nM) in antagonizing the inhibitory adenosine receptor at the hippocampus were similar to their potencies for antagonism of the inhibitory adenosine receptor at the phrenic-diaphragm. XCC was only slightly more potent (K, = 5.4 nM) as an antagonist of the adenosine receptor in the hippocampus than in the phrenic diaphragm. 6. The results suggest that the inhibitory adenosine receptors in the phrenic-diaphragm and in the hippocampus of the rat are similar, and that according to the antagonist potencies, these receptors belong to the A1-adenosine receptor subtype. PMID- 2257447 TI - Proceedings of the British Pharmacological Society meeting. University of Belfast, 12th-14th September 1990. PMID- 2257445 TI - Protein kinase C-mediated contractile responses of arteries from diabetic rats. AB - 1. The role of protein kinase C (PKC) in mediating enhanced contractile responses of aortae and mesenteric arteries from male rats with 12-14 week streptozotocin induced diabetes to noradrenaline (NA) was investigated using the PKC activator, phorbol 12,13-dibutyrate (PDB), and the PKC inhibitor, staurosporine. 2. Maximum contractile responses of aortae and mesenteric arteries from diabetic rats to NA were significantly enhanced compared with responses of arteries from age-matched control animals. The maximum NA responses were increased by 59.6 +/- 7.9% in aortae and by 54.9 +/- 7.4% in mesenteric arteries from diabetic animals, compared to their respective controls. 3. Pretreatment of aortae and mesenteric arteries from both control and diabetic animals with staurosporine (5 x 10(-8) M) caused marked inhibition of contractile responses to a maximum concentration of NA (10(-5) M in aortae; 3 x 10(-5) M in mesenteric arteries). In the presence of staurosporine, no difference was observed in the magnitude of contractile responses of arteries from control and diabetic rats to NA. 4. Maximum contractile responses of mesenteric arteries from diabetic rats to PDB were significantly increased (by 45.0 +/- 4.9%) compared to responses of arteries from control animals. In contrast, no significant difference was found in the magnitude of contractile responses or aortae from control and diabetic rats to PDB. 5. Staurosporine (5 x 10(-8) M caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 x 10(-6) M). In the presence of staurosporine, the difference in magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB was abolished. 6. Contractile responses of aortae and mesenteric arteries from control and diabetic rats to PDB were reduced in the absence of extracellular Ca2", and in the presence of the Ca2 + channel blockers, nifedipine (3 x 10-6 M) or verapamil (3 x 10-6 M). Under these conditions, no difference was found in the magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB. 7. These data suggest that enhanced contractile responses of aortae and mesenteric arteries from streptozotocin-induced diabetic rats to NA may result, at least in part, from increased activation of PKC. In addition, increased activation of PKC-mediated processes, which are dependent on the presence of extracellular Ca2+, may further contribute to the enhanced contractile responses of diabetic mesenteric arteries to NA. PMID- 2257448 TI - Traumatic synovitis analysed by arthroscopy and immunohistopathology. AB - The synovitis induced in previously healthy subjects by knee joint trauma was investigated at arthroscopic surgery performed after 3-70 days. Synovitis was confined to the areas of the synovial membrane bordering the cartilage lesion and displayed a varied intensity of inflammation. Biopsies were sampled under direct vision from the area of the peak inflammatory intensity within each joint and analysed by immunohistopathology. Only sparse lymphocytic infiltration and a slight increase of lining cell layers were found in the biopsies after as long as 70 days. The restricted extent and limited intensity of the inflammatory changes contrast with previous findings in rheumatoid arthritis. However, the arthroscopic and immunohistopathological signs of synovitis were no different. PMID- 2257449 TI - Specific antibody response to the mycobacterial 65 kDa stress protein in ankylosing spondylitis and rheumatoid arthritis. AB - Immune responses to conserved, immunogenic homologues of the mycobacterial 65 kDa stress protein (SP65) have been implicated in inflammatory arthritis. Serum anti SP65 was measured in AS, RA and healthy controls using an indirect enzyme immunoassay with recombinant SP65. IgA anti-SP65 was elevated in 19 of 59 AS patients, but the elevation in median level was not statistically significant. Anti-SP65 of all isotypes was increased in RA, but achieved significance (P less than 0.01) for IgA only. Adjusting specific antibody results for elevations in total serum Ig levels reduced AS and RA anti-SP65 to near normal levels, suggesting that a major component of the increased anti-SP65 may be secondary to polyclonal activation. PMID- 2257446 TI - The crucial role of physiological Ca2+ concentrations in the production of endothelial nitric oxide and the control of vascular tone. AB - 1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denuded donor aortae had no effect on the tone of these tissues. 3. Increasing the concentration of Ca2+ perfusing endothelium-containing donor aortae from zero to 1.25 mM caused a transient (24 +/- 9 min), concentration-dependent basal release of NO, which was attenuated at higher concentrations of Ca2+ (1.5-2.0 mM). 4. The duration of the effect of Ca2+ on the basal release of NO was increased by a concomitant infusion of L-arginine (100 microM) through the donor aorta. 5. Changes in the concentration of Ca2+ between 0.5 and 2.0 mM had a similar biphasic effect on the release of NO induced by ACh, which was also maximal at 1.25 mM Ca2+. 6. When Ca2+ was removed from the Krebs buffer perfusing the donor aorta, the basal release of NO declined within 2 min. In contrast, the release of NO induced by ACh declined progressively over 60 min. 7. Thus changes in the concentration of Ca2+ around the physiological range modulate the synthesis of NO by the vascular endothelium and consequently, vascular tone. This may account for the effects of dietary Ca2+ supplements on the control of some hypertensive states. PMID- 2257451 TI - A laboratory and clinical study of pneumatic 'grip strength' devices. AB - The use of inflated bags or cuffs to measure grip strength is now a well established technique. The method does have a number of problems. Bags of different diameter and volume were seen to give statistically significantly different pressure readings when squeezed by the same subjects. Different initial pressures (from 20 mmHg to 60 mmHg) also gave significantly different results both in laboratory tests on a materials testing machine and when patients with rheumatoid arthritis squeezed the bag. The technique of squeezing also affected the results. Despite the intrinsic drawbacks of the system, it is likely to remain in general use because of familiarity and convenience. We recommend the minimum details required when pneumodynamometer-derived data are published. PMID- 2257450 TI - Intestinal flora of patients with rheumatoid arthritis: induction of chronic arthritis in rats by cell wall fragments from isolated Eubacterium aerofaciens strains. AB - The composition of the obligate anaerobic intestinal flora of patients with rheumatoid arthritis (RA) differed from that of healthy subjects (HS). Total numbers of aerobes as well as anaerobic coccoid rods were found elevated when compared with HS. Eubacterium species were found in all stool samples of both groups; Bifidobacterium species were present in seven (RA) and eight (HS) out of 10 subjects. From the flora of two RA patients and two HS Eubacterium species were isolated and identified. Cell wall fragments from four E. aerofaciens strains (two from RA, two from HS) were tested for arthritis induction in rats. All four strains induced chronic arthritis which was histologically confirmed. We concluded that in the normal intestinal flora of RA patients Eubacterium species are present in high numbers (i.e. greater than 10(9)/g faeces); cell walls from isolated E. aerofaciens strains had arthropathic properties. PMID- 2257453 TI - What could have caused the limping of Hephaestos? PMID- 2257452 TI - The cycling of combination antirheumatic drug therapy in rheumatoid arthritis. AB - In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects. PMID- 2257454 TI - An algometer for the automated measurement of pain threshold. AB - An automated device is described which enables operator independent measurement of pain threshold. Pressure is applied across a joint of the digit by means of a controlled pneumatic actuator. Testing 10 normal subjects indicated good reproducibility (r2 = 0.75, one-way analysis of variance). PMID- 2257455 TI - Autoantibodies in familial Mediterranean fever (recurrent polyserositis). AB - The presence of autoantibodies in our familial Mediterranean fever (FMF) patients was investigated using various immunological techniques. Immunofluorescence screening of 50 FMF sera revealed only one positive for antinuclear antibodies. ELISA assay and nitrocellulose filter assay revealed no difference between FMF sera and healthy controls with regard to the presence of anti-dsDNA antibodies. In Western blotting using HeLa cell extract, FMF patients' sera neither detected anti-Sm, RNP, SSA/Ro, SSB/La antibodies nor any new common band. These findings suggest that it is unlikely that FMF belongs to the family of the autoimmune 'collagen' diseases. PMID- 2257456 TI - Rheumatic diseases may be associated with nephrotic syndrome combined with renal impairment. Should such patients be given a high, low or normal protein diet? PMID- 2257457 TI - The lack of relationship between acetylator phenotype and idiopathic systemic lupus erythematosus in a South-east Asian population: a study of Indians, Malays and Malaysian Chinese. AB - An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status. PMID- 2257459 TI - The medical management of osteoarthritis of the knee: an inflammatory issue? PMID- 2257458 TI - Streptococcal antibody cross-reactivity with HLA-DR4+VE B-lymphocytes. Basis of the DR4 associated genetic predisposition to rheumatic fever and rheumatic heart disease? AB - B-lymphocytes obtained from patients with either rheumatic fever or rheumatic heart disease and from normal subjects were reacted with serum obtained from rabbits immunized with streptococcal cell wall antigen. The presence of cytotoxicity was sought using an inverted phase microscope after differential uptake of eosin dye. The serum was found to be significantly more cytotoxic to HLA-DR4 containing cells of both patients and normals compared with DR4 negative cells (P less than 0.0001). PMID- 2257460 TI - Post-traumatic osteoarthritis--a medico-legal minefield. AB - A consensus view has been obtained from 108 colleagues about four major questions relating to post-traumatic osteoarthritis (OA) posed by a retired judge. In determining the likelihood of OA developing after a fracture, several factors must be taken into account. These include whether the fracture goes through the joint, the resulting angular deformity, the degree of soft tissue damage, the ensuing laxity of the joint, the presence of generalized OA, the involvement of nearby blood vessels supplying the bones of the joint and possibly the degree of immobilization. Lower limb joints are more likely to develop arthritis after injury than arm joints as they carry more load (although it would be wrong to think that arm joints were not load bearing). Occupation is a further factor. Age is thought to be important, with the elderly more at risk immediately, but the younger having longer in which to develop the disease. Younger people are less likely to develop post-traumatic OA, unless there is involvement of the epiphysis or residual angular deformity. Whilst in animals and in some fractures, degenerative changes begin immediately after damage to the joint, in most adults they take at least 2 years. The span is 2-5 years in more severe cases, including fractures of the joint line with a step in the surface, and associated dislocation. Otherwise it may take 10 years. Most of these data are anecdotal or obtained from retrospective surveys. There is great need for prospective work in this field. PMID- 2257461 TI - Remitting seronegative symmetrical synovitis with pitting oedema in young adults: a subset of rheumatoid arthritis or a distinct syndrome? AB - Three young adult patients with seronegative symmetrical polysynovitis affecting the peripheral joints with pitting oedema of both dorsum of hands and feet are described. All of these patients had a benign course and resolved completely within 10-15 months of the onset. None developed any deformities or erosions and/or relapse of arthritis after prolonged follow-up. PMID- 2257462 TI - Ultrasound demonstration of a superior mesenteric artery aneurysm in a patient with Ehlers-Danlos syndrome. AB - A large aneurysm of the superior mesenteric artery was the presumed cause of abdominal pain in an 11-year-old girl with Ehlers-Danlos syndrome. This aneurysm was readily identified by ultrasonography, suggesting that this method could be the diagnostic technique of choice in this disorder. PMID- 2257463 TI - Review of UK data on the rheumatic diseases--4. Gout. PMID- 2257464 TI - Infection and Still's disease. PMID- 2257465 TI - Vasoactive intestinal polypeptide in algodystrophy. PMID- 2257466 TI - Immunological abnormalities in patients with leg ulcers. PMID- 2257467 TI - Raynaud's phenomenon, lack of neurological influence. PMID- 2257468 TI - Raynaud's phenomenon and primary Sjogren's syndrome. PMID- 2257469 TI - Pet ownership: a possible risk factor for scleroderma. PMID- 2257470 TI - Septic arthritis in human immunodeficiency virus infected haemophiliacs. PMID- 2257471 TI - Antinuclear antibodies during pyrithioxine treatment. PMID- 2257472 TI - Splenic size in Behcet's syndrome. PMID- 2257473 TI - Estimating the incidence of SLE. PMID- 2257474 TI - Wegener's granulomatosis in India: not so rare. PMID- 2257475 TI - Reiter's syndrome in a married couple. PMID- 2257476 TI - Thalamic projections from a midbrain somatosensory area in a reptile, Caiman crocodilus. AB - Ascending projections to the thalamus from a midbrain somatosensory area were investigated in a reptile, Caiman crocodilus. Connections were determined utilizing horseradish peroxidase (HRP) neurohistochemistry in which tetramethylbenzidine was the chromogen. Anterograde experiments, in which HRP injections were placed into the midbrain, revealed bilateral projections to the medialis complex of the dorsal thalamus. These observations were confirmed by HRP injections into the medialis complex which retrogradely labeled neurons in the midbrain somatosensory area bilaterally. An ipsilateral predominance of connections was observed in both anterograde and retrograde HRP experiments. This somatosensory target in the thalamus, the medialis complex, is located between the auditory and visual nuclei. This organization and neural circuitry of somatosensation is similar to that of auditory and visual systems that terminate in the midbrain of Caiman. PMID- 2257477 TI - Phylogeny of putative cholinergic visual pathways through the pretectum to the hypothalamus in teleost fish. AB - Three patterns of pretectal organization can be discerned morphologically in teleosts. The taxonomic distribution of these pretectal patterns suggests that the intermediately complex pattern (seen in most teleost groups) has given rise to both the elaborate pattern (seen in percomorphs) and the simple pattern (seen in cyprinids). Two pretectal patterns (intermediately complex and elaborate) form part of similar, homologous visual pathways to the hypothalamus; the third pattern is involved in a nonhomologous pathway to the hypothalamus. Acetylcholinesterase (AChE) histochemistry was used in the present study in order to characterize these pretectal patterns further. It is demonstrated that AChE is a highly selective and reliable interspecific marker for all divisions of the superficial pretectum, the nucleus corticalis, the posterior pretectal nucleus (or nucleus glomerulosus) and portions of the inferior lobe. Therefore, the histochemical data support the hypothesis of a homology between the three patterns of pretectal organization in teleosts. Furthermore, the present data provide a basis for more specific investigations regarding the involvement of acetylcholine as a neurotransmitter within the visual pathways to the hypothalamus in teleosts. PMID- 2257478 TI - Retinofugal projections in a marsupial, Tarsipes rostratus (honey possum). AB - We examined the mature retinal projections of the honey possum, Tarsipes rostratus, an Australian, diprotodont marsupial, using uni-ocular injections of horseradish peroxidase and tetramethylbenzidine processing. The suprachiasmatic nucleus, medial, lateral and dorsal terminal nuclei of the accessory optic tract, pretectal nuclei and superior colliculus received bilateral retinal input. Contralateral input only was observed in the lateral posterior nucleus. The pattern of input to these regions was essentially similar to that seen in other marsupials. Cyto-architectural examination of the dorsal lateral geniculate nucleus (dLGN) indicated that 5 laminae were present in the alpha-segment, but the beta-segment appeared to lack lamination. Input to the dLGN was bilateral, overlapping considerably, and was organised in a laminar fashion with 7 and 3 terminal bands in the alpha- and beta-segments, respectively. The monocular segment accounted for 12% of the total volume of the dLGN. In the alpha-segment, 2 terminal bands each received exclusively contralateral or ipsilateral input and 3 bilateral input. In the beta-segment, 2 terminal bands received bilateral and 1 contralateral input. The volumes of the nucleus receiving contralateral and ipsilateral input were 77 and 54% of the total, respectively. A marked overlap of input from the two eyes is an unusual feature for a diprotodont marsupial and has previously been seen only in the feathertail glider. Our findings for the dLGN are of interest in the light of recent serological and taxonomic studies which suggest a close link between the feathertail glider and the honey possum. PMID- 2257479 TI - Afferent connections of the striatum and the nucleus accumbens in the lizard Gekko gecko. AB - The afferent connections of the striatum and the nucleus accumbens of the lizard Gekko gecko were studied with retrograde tracing by means of horseradish peroxidase and Fluoro-Gold and with anterograde tracing by means of Phaseolus vulgaris leukoagglutinin. The striatum receives projections from the cortex, the dorsal ventricular ridge, the lateral amygdaloid nucleus, the globus pallidus, the anterior peduncular nucleus, the ventral tegmental area and substantia nigra, the area ventral to the substantia nigra, and the dorsal thalamus. The nucleus accumbens is projected upon by the cortex, the diagonal band, the ventral pallidum, the lateral preoptic area, the ventral tegmental area, and the dorsal thalamus. The source of the cortical projection to the striatum and the nucleus accumbens is a longitudinal zone in the dorsal cortex that, rostrally in the hemisphere, is located medially and, more caudally, in its middle one third. The medial and rostrolateral areas of the dorsal ventricular ridge each project to the striatum in a vertical zone. The fibers from the caudolateral area of the ridge end in two oblique bands located parallel to the border between the dorsal ventricular ridge and the striatum. The pathways from the mesencephalic tegmentum to the striatum and the nucleus accumbens show a medial to lateral topography. This is similar to the situation in birds, but contrary to that in mammals in which these pathways are extensively interconnected. The specific sensory nuclei of the dorsal thalamus were found to project not only to the dorsal ventricular ridge, but also, and in a topographical fashion, to the striatum. The dorsomedial thalamic nucleus, which innervates the dorsal ventricular ridge, has additional projections to the striatum and the nucleus accumbens. This projection pattern is similar to that of the intralaminar thalamic nuclei of birds and mammals. PMID- 2257480 TI - Distribution of phenylethanolamine-N-methyltransferase-immunoreactive perikarya and fibers in the brain of the lizard Gekko gecko. AB - The distribution of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive (PNMTi) cell bodies and fibers in the brain of the lizard Gekko gecko was studied by antibodies raised in rabbits against purified bovine adrenal PNMT. The PNMTi cell bodies were observed in the ventrolateral rhombencephalic tegmentum at the level of the obex. No immunoreactive perikarya were found in the nucleus of the solitary tract, the medial longitudinal fascicle or the hypothalamus. An extensive network of PNMTi fibers is present throughout the brain, extending rostrally as far as the olfactory peduncle. In the telecenphalon, moderate to dense plexuses of PNMTi fibers were observed in the medial part of the nucleus accumbens, the medial septal nucleus, the nucleus of the diagonal band, the caudoventral septal region and the central amygdaloid nucleus. In the diencephalon, the periventricular and lateral zones of the preoptic and hypothalamic areas, the medial forebrain bundle and the dorsomedial thalamic nucleus contain many PNMTi fibers. Brainstem structures innervated by PNMTi fibers are the ventral tegmental area, the substantia nigra, the periaqueductal gray, the locus coeruleus, the parabrachial region, the nucleus of the solitary tract, the dorsal motor nucleus of the vagus and the ventrolateral region of the caudal brainstem. Although the brain of Gekko appears to lack PNMTi cells in areas comparable to the C2 and C3 cell groups in rats, the distribution of PNMTi fibers is nevertheless strikingly similar in both groups. PMID- 2257481 TI - Cytoplasmic matrix proteins in central nervous system presynaptic terminals: turnover and effects of osmotic lysis. AB - Cytomatrix proteins, of primary functional importance in central nervous system neuron terminals, are provided to their site of action in the terminal by axonal transport. Slow component b (SCb) of axonal transport has been proposed to be the biochemical counterpart of the moving cytoplasmic matrix, or cytomatrix, in axons. In the current study, axonally transported SCb proteins destined for neuron terminals were pulse-radiolabeled with [35S]methionine in guinea pig retinal ganglion cells. After SCb proteins reached the terminals in the superior colliculi, synaptosomes were prepared to distinguish between SCb proteins in the preterminal axons and those of the presynaptic terminals. Study of the initial entry and turnover of individual SCb proteins in presynaptic terminals revealed different residence times of certain SCb proteins in comparison with their cohorts. Preliminary information about the structural relationships of the proteins comprising the presynaptic cytomatrix was obtained by examining the solubility of individual SCb proteins relative to other SCb proteins, or membranes from osmotically lysed terminals. Last, treatment of those radiolabeled synaptosomes with varying concentrations of salts was performed to determine possible effects on observed structural relationships. PMID- 2257482 TI - Transferrin expression in myelinated and non-myelinated peripheral nerves. AB - Transferrin and its receptor are involved in the delivery of iron to most cells. Previous studies have demonstrated that transferrin is associated with oligodendrocytes, the myelin-producing cells in the central nervous system. In the peripheral nervous system, the Schwann cell produces myelin. This study used immunohistochemistry and immunoblot analysis to determine whether expression of transferrin is unique to myelinated peripheral nerves. Immunohistochemical examination demonstrated cytoplasmic accumulation of transferrin in Schwann cells of the myelinated sciatic nerve, but not in the unmyelinated cervical sympathetic trunk. Immunoblot analysis revealed there is 10 X the amount of transferrin in the sciatic nerve compared to the cervical sympathetic trunk. These results are consistent with the hypothesis that transferrin may play a role in myelination. PMID- 2257483 TI - Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats. AB - Inhibition of noxious heat-induced tail flick by electrical stimulation of the arcuate nucleus of the hypothalamus (ARH) was examined and characterized in pentobarbital-anesthetized rats. Systematic mapping studies revealed that inhibition of the tail flick reflex could be induced by stimulating widespread areas in the ventromedial parts of the hypothalamus, which include the paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, anterior hypothalamic area as well as the ARH areas. The ARH stimulation-produced tail flick suppression could be completely blocked by systemic naloxone (2 mg/kg) which shows the involvement of an opiate mechanism in this effect. Although the tail flick reflex in the lightly anesthetized state is of significantly shorter latency than in the unanesthetized state, thresholds of the ARH stimulation for suppressing spinal nociceptive reflexes in the lightly anesthetized state were not significantly different from the thresholds at the same ARH sites in the awake state. PMID- 2257484 TI - Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. AB - Prolonged neurological dysfunction that results from an insult to the brain is often attributed to irreversible structural damage such as loss of neurons or axonal degeneration. For example, following cerebral ischemia even partial hippocampal CA1 neuronal loss has been proposed to be sufficient to result in deficits in hippocampal dependent spatial memory. This study examined if hippocampal CA1 neuronal loss and/or axonal injury was necessary to produce prolonged spatial memory deficits resulting from traumatic brain injury (TBI). Prior to TBI Sprague-Dawley rats were trained on an 8-arm radial maze, a task sensitive to detecting specific lesions of the hippocampus or its extrinsic connections. Following a mild, moderate, or sham injury, rats were tested for working and reference memory for 25 days. After 25 days of maze testing, histological cell counts were made from consistent coronal sections of the mid dorsal hippocampus. Rats subjected to mild or moderate TBI manifested working memory deficits for 5 and 15 days, respectively, after injury in the absence of overt (all brain regions) or quantitative (CA1 only) evidence of neuronal death. The number of CA1 pyramidal neurons of representative sections of the mid-dorsal hippocampi for injured maze-deficit rats and sham control rats were: 1626 (S.E.M. = +/- 66) and 1693 (S.E.M. = +/- 69) per 10(6) micron2, respectively. Additionally, no overt evidence of axonal injury was observed in any forebrain structure including major intrinsic or extrinsic connecting hippocampal pathways. These data strongly suggest that mild to moderate TBI is capable of producing prolonged spatial memory deficits in the rat without evidence of either neuronal cell death in the intrinsic hippocampus or overt axonal injury in hippocampal pathways. PMID- 2257486 TI - Expiration-related neurons in the caudal ventral respiratory group of the cat: influences of the activation of Botzinger complex neurons. AB - The functional role of Botzinger complex (Bot. c.) projections to the expiration related (ER) area of the caudal ventral respiratory group (cVRG) was investigated in anesthetized, vagotomized, paralyzed and artificially ventilated cats. ER neurons in both the ipsi- and the contralateral cVRG displayed excitatory responses to Bot. c. electrical microstimulation. They were also activated by microinjections of D,L-homocysteic acid into the Bot. c. region. We propose that at least part of the Bot. c. projections to the cVRG have an excitatory function. PMID- 2257485 TI - Differentiation of central cholecystokinin receptor binding sites using the non peptide antagonists MK-329 and L-365,260. AB - Cholecystokinin (CCK) receptor binding was measured in rodent and primate brain and spinal cord using 125I-Bolton Hunter CCK-8 (125I-BH-CCK) and the selective non-peptide CCK antagonists MK-329 and L-365,260. In homogenate binding studies, L-365,260 displayed nanomolar affinity for CCK-B receptors in the cerebral cortex of several species including man (pIC50 congruent to 8.2) but showed low affinity for CCK-A receptors in the rat pancreas (pIC50 congruent to 6.3). By contrast, the CCK-A antagonist MK-329 showed the reverse selectivity (cortex: pIC50 congruent to 6.9, pancreas: pIC50 = 9.6). In autoradiographs of rat and monkey brain. 125I-BH-CCK binding was localized regionally with high levels being detected in the cerebral cortex, basal ganglia and some mid- and hindbrain nuclei. Specific 125I-BH-CCK binding was also localized to the substantia gelatinosa of the rat, monkey and human spinal cord. L-365,260 inhibited binding to most areas of the brain, but in the rat medial nucleus tractus solitarii and the monkey nucleus tractus solitarii. dorsomedial nucleus and infundibular hypothalamic nuclei together with the dorsomedial aspects of the caudate nucleus, where CCK-A sites are present, L-365,260 failed to displace all 125I-BH-CCK binding. In the primate spinal cord, L-365,260 was a relatively weak inhibitor of 125I-BH-CCK binding (pIC50 congruent to 6.0) whereas MK-329 showed high affinity for the CCK-A sites present there (pIC50 congruent to 9.6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257487 TI - Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K. AB - The distribution of calbindin-D28K (CaBP)-positive neurons was investigated by immunohistochemistry in 4 controls, 5 cases of Parkinson's disease and a single case of strionigral degeneration. CaBP-positive neurons were preferentially localized to the mediodorsal portion of the substantia nigra pars compacta (SNC) in the beta layer, while CaBP-negative, melanin-positive neurons were concentrated in the ventrolateral SNC in the alpha layer. In Parkinson's disease and the case of strionigral degeneration, there was a relative sparing of the CaBP-positive neurons compared with CaBP-negative, pigmented neurons. These data imply that CaBP may confer some protection to SNC dopaminergic neurons against the pathological process which is responsible for Parkinson's disease and strionigral degeneration. PMID- 2257488 TI - Changes in axonal impulse conduction correlate with sensory modality in primary afferent fibers in the rat. AB - Conduction velocity was measured in vivo in single cutaneous afferent fibers of rat sciatic nerve that were characterized by natural stimulation. During sustained electrical stimulation, impulses slowed less and propagated more reliably in cold fibers (both A delta and C) than in nociceptive fibers of similar conduction velocity. Velocity in cold fibers tended to stabilize after an initial decrease rather than decrease throughout the stimulation as for nociceptive fibers. The slowing correlated with axon modality and hence with natural firing pattern, raising the possibility that impulse activity can determine conduction properties of axons. PMID- 2257489 TI - Anticonvulsant action of an arylamine-containing fraction from Agelenopsis spider venom. AB - A low molecular weight fraction (AG2) containing arylamine compounds has been isolated from venom of the spider Agelenopsis aperta. When administered intravenously or intracerebroventricularly, AG2 produces dose-dependent suppression of behavioral convulsions induced in rats by kainic acid, picrotoxin, or bicuculline. The low molecular weight compounds in spider venoms may provide novel tools for anticonvulsant research and therapy. PMID- 2257490 TI - The conduction velocity and segmental distribution of afferent fibers in the rectal nerves of the female rat. AB - The conduction velocity and segmental distribution of afferent fibers in the rectal nerves of the female rat were determined. These afferent fibers had conduction velocities ranging from 0.5-23.5 m/s (Mode = 0.5 m/s; Median = 1 m/s). Sixty-six percent of the fibers had conduction velocities less than 2.5 m/s and were thus considered to be unmyelinated. Of a total of 135 afferent fibers studied, only 5 (4%) were found in the L6 dorsal root, whereas 130 (96%) were found in the S1 dorsal root. Neuroanatomic tracing studies (Fluoro-Gold applied to the transected rectal nerves) labelled an overwhelming majority of neurons in the S1 dorsal root ganglion, confirming the results of the conduction velocity experiments. Although the conduction velocity distribution of afferent fibers in the rectal nerves is similar to that of the afferent fibers innervating the bladder, the segmental distribution is quite different since most of the bladder afferent fibers (84%) were found in the L6 dorsal root. PMID- 2257491 TI - Analgesic, anesthetic, and respiratory effects of the competitive N-methyl-D aspartate (NMDA) antagonist CGS 19755 in rhesus monkeys. AB - The competitive excitatory amino acid antagonist cis-4-phosphonomethyl-2 piperidine-carboxylic acid (CGS 19755) increased the latency for monkeys to remove their tails from warm water (analgesia); larger doses produced ataxia, loss of righting, salivation, and eliminated reactivity to stimulation (anesthesia). CGS 19755 decreased tidal volume and had little effect on frequency of respiration. Although longer lasting, the effects of CGS 19755 were similar to the effects of ketamine, suggesting these effects result from actions at the NMDA receptor complex. PMID- 2257493 TI - An expert system for diagnosis of coronary artery stenosis based on 201Tl scintigrams using the Dempster-Shafer theory of evidence. AB - An expert system for the diagnosis of stenoses in the three main coronary arteries (left anterior descending, right coronary artery and circumflex) is described. First, the knowledge base domain--201Tl scintigrams--is explained and the method of preprocessing the original heart images is given. Next, the method of dealing with the uncertainties present both in the cardiologist-specified rules and the data using the Dempster-Shafer theory of evidence is explained. Finally, the constructed expert system and the results are discussed and several graphical examples are shown. PMID- 2257492 TI - Efficient recognition of immunoglobulin domains from amino acid sequences using a neural network. AB - A neural network was trained using back propagation to recognize immunoglobulin domains from amino acid sequences. The program was designed to identify proteins exhibiting such domains with minimal rates of false positives and false negatives. The National Biomedical Research Foundation NEW protein sequences database was scanned to evaluate the performance of the program in recognizing mouse immunoglobulin sequences. The program correctly recognized 55 out of 56 mouse immunoglobulin sequences, corresponding to a recognition efficiency of 98.2% with an overall false positive rate of 7.3%. These data demonstrate that neural network-based search programs are well suited to search for sequences characterized by only a few well-conserved subsequences. PMID- 2257494 TI - SPLICE, a computer program for automated extraction of information from GenBank sequence entries. AB - SPLICE, a software tool for the extraction of sequences from files in GenBank tape format, has been developed. The program can analyze the features table in this format and use any of the information provided to write the corresponding sequences into a standard sequence file format suitable for use with sequence analysis programs. Sequences that are present as several subsequent fragments in a single GenBank file, such as those encoding a peptide, can be spliced together by the program. Further, sequences that are present in more than one Genbank file, such as an exon which spans several different files, can also be spliced into one sequence. SPLICE runs under the MS/DOS and Unix operating systems, can be called as a sub-process by other programs and can process batches of files. PMID- 2257495 TI - Exact computation of pattern probabilities in random sequences generated by Markov chains. AB - Observed patterns in macromolecular sequences are often considered as words and compared with their probabilities of occurring in random sequences. Calculation of these probabilities, however, often lacks rigour. We have developed an algorithm for exact computation of such probabilities for stochastic sequences that follow a Markov chain model. The method is applicable to the case that a random sequence contains one out of two given patterns P and Q, or both simultaneously. Another application yields the probability function P(x) that a sequence contains pattern P exactly x times. An application to patterns that include wild-card characters yields probabilities for homonucleotide clusters of a given length. We prove the probability of multiple runs of single nucleotides in the SV40 genome to be in accordance with the dinucleotide composition of the sequence, although it is in conflict with mononucleotide composition. PMID- 2257496 TI - BISANCE: a French service for access to biomolecular sequence databases. PMID- 2257497 TI - Finding hydrophobic microdomains using an object-oriented database. AB - A procedure for finding clusters of adjacent residues in protein hydrophobic cores--hydrophobic microdomains--has been proposed by Plochocka et al. A program is presented that finds hydrophobic microdomains, making use of protein structure data stored in an object-oriented database and the list-processing features of Prolog. Alternative definitions for hydrophobic microdomains are explored. Results are presented for haemoglobin. PMID- 2257498 TI - Structure detection through automated covariance search. AB - This paper summarizes our investigations into the computational detection of secondary and tertiary structure of ribosomal RNA. We have developed a new automated procedure that not only identifies potential secondary and tertiary structural interactions, but also provides the covariation evidence that supports the proposed bondings, and any counterevidence that can be detected in the known sequences. A small number of previously unknown higher-order structural features have been detected in individual RNA molecules (16S rRNA and 7S RNA) through the use of our automated procedure. We are systematically studying mitochondrial rRNA, seeking tertiary structure within 16S rRNA and quaternary structure between 16S and 23S rRNA. To test hypotheses suggested by an examination of our program's output, our colleagues in biology are sequencing key portions of the 23S ribosomal RNA for species in which the known 16S ribosomal RNA exhibits variation (from the dominant pattern) at the site of a proposed bonding. Our ultimate hope is that automated covariation analysis will contribute significantly to a refined picture of ribosomal structure. PMID- 2257499 TI - A space-efficient algorithm for local similarities. AB - Existing dynamic-programming algorithms for identifying similar regions of two sequences require time and space proportional to the product of the sequence lengths. Often this space requirement is more limiting than the time requirement. We describe a dynamic-programming local-similarity algorithm that needs only space proportional to the sum of the sequence lengths. The method can also find repeats within a single long sequence. To illustrate the algorithm's potential, we discuss comparison of a 73,360 nucleotide sequence containing the human beta like globin gene cluster and a corresponding 44,594 nucleotide sequence for rabbit, a problem well beyond the capabilities of other dynamic-programming software. PMID- 2257500 TI - Object-centered representation for species systematics and identification in living systems in nature. AB - An artificial intelligence application to identification in biological taxonomy is presented. An object-centered representation is described using SHIRKA, a knowledge-based system developed in France. The capacities of this system, relating to a classification algorithm, are described. An application to the identification of the trees and lianas of the evergreen forests of the Western Ghats (India) is presented to illustrate the problems encountered in the development of the knowledge base. A model of a systematist's reasoning, using evolutionary principles, is the basis of this work. Finally the efficiency of the system is discussed. PMID- 2257501 TI - An improved sequence handling package that runs on the Apple Macintosh. AB - We report improvements to our sequence analysis package and adaptation to run on the Apple Macintosh range of machines. The 'standard' version of the programs, which run on a VAX, has been given a new user interface that makes the programs very much easier to work with and has facilitated the move to the Macintosh. The reorganization of the code should simplify moves to other systems that offer WIMP user interfaces. In addition to a large number of small but useful extra features, some important new analytical functions have been devised. These include sequence and contig editors; optimal alignment and comparison methods; and a new method for comparing the observed and expected frequencies of selected oligonucleotides. PMID- 2257502 TI - A program to optimize DNA sequences for protein expression. PMID- 2257503 TI - Multiple sequence editing by spreadsheet. PMID- 2257504 TI - PROLANG: the SCAN command. PMID- 2257505 TI - Three-dimensional lithographic model building from volume data sets. AB - Computed tomographic images of a dry human skull and an in-situ knee joint were used to construct solid three-dimensional polymer models using stereolithographic techniques that have been introduced recently into the manufacturing industry. The stereolithographic technique makes use of a computer-steered narrow laser beam to solidify the model within a bath of liquid photocurable polymer. The method does not suffer from the cutting-tool size and path constraints encountered in the more commonly used process of machining the models from a solid block of foam. PMID- 2257506 TI - Computed tomography and lateral ventricular asymmetry: clinical and brain structural correlates. AB - Asymmetry of the ventricles of the brain without an obvious cause is a common and intriguing radiologic finding. To understand this phenomenon better the authors conducted a 24-month study to compare clinical and structural manifestations of two groups of patients who had undergone head computed tomography (CT): group A comprised 249 patients with asymmetry of the lateral ventricles of the brain without space-occupying lesions, intracranial bleeding, recent infarction or trauma and group B comprised 266 patients with the above exclusion criteria but without ventricular asymmetry. The degree of ventricular asymmetry was classified as mild, moderate or severe, according to the ratio of the larger frontal horn diameter to the smaller one. The incidence of lateral ventricular asymmetry was 5.3%. The following clinical manifestations were more frequently present in group A: headaches (p = 0.002), seizures (p = 0.007) and positive human immunodeficiency virus (HIV) status (p = 0.02). Transient ischemic attacks were more prevalent in group B (p = 0.009). Independent predictors of headache were: younger age (p less than 0.001) and the degree of ventricular asymmetry (p = 0.02). Predictors of seizures were: younger age (p less than 0.001), ventricular asymmetry (p = 0.004) and the absence of septal deviation (p = 0.009). In group A, predictors of a higher degree of asymmetry were septal deviation (p less than 0.001) and older age (p = 0.008). The authors conclude that asymmetry of the lateral ventricles of the brain is a relatively common CT finding that has important clinical and brain structural correlates and deserves more attention in the field of imaging. PMID- 2257507 TI - Ureteral valves: preoperative radiologic diagnosis. AB - The authors report two cases of congenital ureteral valves that were diagnosed preoperatively in adults. The radiologic, operative and histologic findings are described. A short review of the available literature is also presented. The importance of a confident radiologic diagnosis of this congenital anomaly is emphasized. PMID- 2257508 TI - Pyocystis with urethral obstruction: percutaneous cystostomy as an alternative to surgery. AB - Three patients with pyocystis and urethral obstruction were successfully treated with percutaneous placement of a suprapubic cystostomy catheter. This approach is an alternative to transurethral bladder irrigation or cystectomy in selected patients. PMID- 2257509 TI - Disseminated lymphatic tuberculosis in acquired immunodeficiency syndrome: computed tomography findings. AB - There is an increased frequency of disseminated tuberculosis in patients with acquired immunodeficiency syndrome (AIDS). The authors reviewed 6 thoracic and 10 abdominal computed tomography scans from 11 patients who had AIDS and disseminated tuberculosis. All scans demonstrated multiple, large, mediastinal or retroperitoneal lymph nodes, or both; low-density centers within enlarged nodes were identified in seven patients (63%). The scans also showed a diffuse miliary pattern (three patients), pericardial effusion (three patients), mild hepatomegaly (six patients), moderate splenomegaly (seven patients), hypodense splenic lesions (one patient), peritoneal fluid (four patients), bowel involvement (two patients) and dilatation of the biliary tract (two patients). Infection with Mycobacterium tuberculosis was demonstrated in all cases. The findings of this study show that lymph-node enlargement and nodes with low density centers in patients who have AIDS are suggestive of disseminated tuberculous infection. PMID- 2257510 TI - Atypical collapse of the upper lobe of the right lung simulating combined right upper and middle lobe collapse: report of two cases. AB - The authors describe two cases of collapse of the upper lobe of the right lung simulating the appearance on plain chest radiographs of collapse of the right upper and middle lobes combined. Computed tomography and bronchoscopy in both cases and surgery in one case showed that the middle lobe was normal. Possible mechanisms for this appearance on plain chest radiographs include the presence of adhesions between the obstructed upper lobe and pleura and the presence of obstructive pneumonia in the upper lobe, preventing typical collapse. PMID- 2257511 TI - Ultrasonography and radiography in the diagnosis of Peyronie's disease. AB - In this study the authors compare ultrasonography and radiography with clinical examination in the diagnosis of Peyronie's disease. They also review its clinical presentation. In contrast to previous studies they found no correlation between plaques found on ultrasonography or radiography and those found on clinical examination. They conclude that ultrasonography and radiography are not reliable in diagnosing Peyronie's disease. PMID- 2257512 TI - Pulmonary sclerosing hemangioma: unusual cause of a solitary pulmonary nodule. AB - Pulmonary sclerosing hemangiomas are rare, benign neoplasms, which are usually solitary. The authors describe the computed tomography-pathological correlation in a case of pulmonary sclerosing hemangioma. Computed tomography demonstrated a smoothly marginated, homogeneously enhancing nodule, 1.5 cm in diameter. Pathologically the lesion was well circumscribed, soft and hemorrhagic on its cut surface. Microscopic examination revealed a sclerosing hemangioma, predominantly of the hemorrhagic type. PMID- 2257514 TI - Mediastinal Castleman's disease: demonstration with computed tomography and angiography. AB - The authors report a case of Castleman's disease in the mediastinum that was discovered in a young woman receiving high-dose steroids for oral pemphigus vulgaris. Computed tomography demonstrated that the mass was calcified and was markedly enhanced after intravenous injection of contrast material, a manifestation of the hyaline-vascular histologic variant. Arteriography proved invaluable in planning the surgical approach to this highly vascular mass. Because Castleman's disease is rare most radiologists are not familiar with the radiographic features and are unaware that profuse hemorrhage may complicate biopsy and surgery. PMID- 2257513 TI - Agenesis of the corpus callosum and colloid cyst of the third ventricle: magnetic resonance imaging of an unusual association. AB - Agenesis of the corpus callosum is usually associated with brain malformations or with anomalies outside the central nervous system. A colloid cyst of the third ventricle may give rise to hydrocephalus and even sudden death. The authors report the case of a 23-year-old man in whom both these uncommon conditions coexisted. The findings on computed tomography and magnetic resonance imaging are described. The colloid cyst was completely excised through a frontal craniotomy and the patient made a smooth recovery. PMID- 2257515 TI - Radiation-induced malignant pleural mesothelioma. AB - Malignant pleural mesothelioma is a rare and usually fatal disease. Its association with asbestosis is well recognized. The authors report a case of malignant pleural mesothelioma that developed 30 years after the patient underwent radiotherapy for breast cancer. This appears to be the first such case reported in the radiology literature. PMID- 2257516 TI - Darkroom transplant. AB - Manual film processing systems produce their own types of artefacts. The authors report accidental transfer of an image-bearing emulsion from one film to another. The films were lying in close apposition in the darkroom washing tank. Forcible separation of the two films resulted in the "transplant". PMID- 2257517 TI - Aluminium may cause senile dementia and bone fragility. PMID- 2257518 TI - A model of osteon closure in cortical bone. AB - A model of osteon closure is presented that incorporates some physiologic features of cortical bone remodeling, such as matrix synthesizing activity of osteoblasts, their burial as osteocytes, and elimination of cells. A simplified version of the model assumes a constant osteoblast activity throughout radial closure. An extended version allows for variable osteoblasts activity and is based on Lee's law of radial closure kinetics. The model calculations (extended model) show that both in humans and beagle dogs osteoblast activity steadily decreases during radial closure of the osteon. The potential of the model is also illustrated by calculating the dynamic change of the geometrical shape of the closing cone and the time dependence of the osteoid seam width, number of osteoblasts and bone formation rate in the closing cone. PMID- 2257519 TI - Bone death in hip fracture in the elderly. AB - We examined femoral head bone from 50 cadavers and from 21 patients who had suffered pathologic fracture of the femoral neck. We used a histochemical technique for lactate dehydrogenase (LDH) activity to demonstrate osteocyte viability. The femoral heads were removed within 36 hours of death or fracture, as LDH activity persists in the cytoplasm of viable cells for this time at 37 degrees after interruption of the blood supply. In the controls, there was an age related reduction in mean osteocyte viability, from 88 +/- 7% (mean +/- SD) at age 10-29 years to 58 +/- 12% at age 70-89 years. In the hip fracture patients, mean osteocyte viability was 58 +/- 21% but there was much variability in both osteocyte viability and bone mass. In 5 fracture patients, there was extensive osteocyte death, suggesting that most of the femoral head bone was nonviable; these patients had little microfracture callus. Others had predominantly viable bone which was usually osteoporotic, and their bone frequently showed microfracture callus. Osteomalacia was not seen in any patient. It is suggested that bone death, in addition to osteoporosis, may sometimes contribute to hip fracture in the elderly. PMID- 2257520 TI - Monolayer cultures of normal human bone cells contain multiple subpopulations of alkaline phosphatase positive cells. AB - Cytochemical staining of normal human bone cells in monolayer cultures for alkaline phosphatase (ALP) indicated that the cultures contained mixed-cell populations. Time course evaluations of the cytochemical staining revealed, in addition to the ALP-negative cell population, at least two subpopulations of ALP positive human bone cells with different levels of ALP. A cytochemical method has been developed which separates the ALP-positive cells into high and intermediate ALP subpopulations. In this method, human bone cells were stained for ALP using an azo-dye method and incubating at 4 degrees C for 10 and 30 minutes, respectively. We defined the cell population that stained positively for ALP at 10 minutes as strong ALP-positive cells, and both strong and intermediate cells were stained at 30 minutes. The intermediate cells were determined from the difference between the values at the two time points. The intra- and interassay variations of the assay, with the same investigator in blinded investigations, were both less than 10% and the interobserver variation was approximately 25%. Analysis of the distribution of ALP levels in cells with a laser densitometer confirmed the presence of at least three cell subpopulations. 1,25(OH)2D3 treatment increased the proportions of both ALP-positive cell populations, whereas TGF-beta treatment increased only the intermediate ALP-positive cell population. On the contrary, fluoride increased the proportion of the strong ALP cells, and IGF-1 had no effect on the proportions of either ALP-positive subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257521 TI - Diurnal rhythm and 24-hour integrated concentrations of serum osteocalcin in normals: influence of age, sex, season, and smoking habits. AB - In the present study we examined whether the diurnal pattern and the 24-hour integrated serum concentration of osteocalcin (S-OC(I] showed any variation due to age, sex, season, or smoking habits in 31 normal subjects, aged 23-47 years. Blood samples were drawn every 60 minutes from 4 p.m. until 6 p.m. the following day. Serum osteocalcin showed diurnal variation as described earlier but no influence of age or sex on the diurnal variation could be demonstrated. Ten subjects were smokers, all consuming more than 10 cigarettes daily, but the diurnal variation in OC with time was not different from an age-, sex-, and height-matched group of strictly nonsmokers. Sixteen of the subjects were initially examined in March and 15 in November. Eight subjects were examined during a period in both November and March, and 5 of these went through an additional study period in July. These seasonal studies showed that the diurnal time course pattern during different seasons of the year were statistically indistinguishable from each other. The S-OC(I) was significantly higher in subjects below 29 years of age compared with subjects aged 30-40 years (P less than 0.01). Men had higher values than women (P less than 0.05). Moreover, S OC(I) was higher in November compared to March (P less than 0.05). There was no effect of smoking on S-OC(I). A significant correlation existed between S-OC(I) and age (r = 0.50, P less than 0.005). Multiple regression showed that among age, height, and weight, only age and height were significant determinants for S-OC(I) (r = 0.50, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257522 TI - Antacid and sucralfate-induced hypophosphatemic osteomalacia: a case report and review of the literature. AB - A 42-year-old woman presented to our institution with a 2-week history of bone pain in the lower extremities. Her history was remarkable for duodenal ulcer and long-term treatment with a magnesium-aluminum hydroxide antacid (Maalox) and sucralfate. Initial laboratory studies showed severe hypophosphatemia and elevated alkaline phosphatase and serum 1,25-dihydroxyvitamin D levels. Bone scan showed multiple areas of increased uptake consistent with osteomalacia and microfractures. The patient recovered completely following withdrawal of antacids and sucralfate and short-term treatment with phosphate. Although hypophosphatemia induced by aluminum-containing antacids is rare, treatment of peptic ulcer disease with a combination of two aluminum-containing agents may increase the risk of clinically significant hypophosphatemia. Awareness of this condition is important, because early recognition can prevent morbidity and lead to safe and effective treatment. PMID- 2257523 TI - A generalized procedure for predicting bone mass regulation by mechanical strain. AB - Understanding of the mechanisms that control the modifications of the bone weight bearing attitude in response to external load conditions attracted considerable attention from researchers in the biological, medical, and radiological fields. This study presents a general approach for predicting the reaction of the bone tissue to cyclic loads with different intensity and temporal distribution. Empirical relationships are generated that incorporate the wealth of published experimental data, obtained from in vivo, ex vivo, and in vitro studies, into an integrated analysis. The developed procedure was guided by and is in close agreement with the published experimental data. The approach provides a general framework for predicting the effect of mechanical strain deviation from the physiological strain environment only, without consideration of the influence of any other changes in the biochemical, physiological, or psychological mechanisms controlling bone growth and damage. Further clinical investigations with controlled exercise and systematic bone scanning are necessary to check the applicability of the coefficients generated in the proposed method for general use on human subjects. PMID- 2257524 TI - A potassium channel in cultured chondrocytes. AB - Chondrocytes, obtained from preosseous cartilage, were studied by patch clamp technique in cell-attached recording configuration, and single potassium channels were characterized at different stages of culture. After 3 days, outward currents were present, with an open probability increasing with depolarization, and the K+ channels showing a mean slope conductance of 82 pS in asymmetric and 168 pS in symmetric potassium solution. Tetraethylammonium (TEA) and quinidine blocked the channels. Cells at confluence showed similar channel activity, with conductances of 121 and 252 pS, respectively. We suggest that culture time and/or conditions may modify K+ channels or induce the expression of a new type of channels. PMID- 2257525 TI - Effects of a high fat-sucrose diet on cortical bone morphology and biomechanics. AB - High fat-sucrose (HFS) diets can reportedly produce glucose intolerance and hyperinsulinemia that may indirectly have deleterious effects on bone. The effects of a high-fat diet on calcium absorption, bone calcium content, and bone mechanical properties, however, remain controversial. Thus, we examined the morphological and biomechanical adaptations in limb bones of rats that were fed a HFS diet. Female Sprague-Dawley rats (8 weeks old) were randomly assigned to two groups, either a control group (n = 9) fed a standard diet (low-fat complex carbohydrate) or an experimental group (n = 9) fed a HFS diet for 10 weeks. The right tibia and second metatarsus (MT) were fractured in three-point bending, and contralateral bones were used for morphological and histological analyses. HFS tibias had significantly lower maximum load and failure energy, and tensile stress at the proportional limit for both HFS tibia and MT was significantly less than controls. In addition, the elastic modulus and density of the HFS MT was significantly lower than controls. Geometry of the tibial mid-diaphysial cross section did not differ for the two diets, but the cortical cross-sectional area of HFS MT increased significantly compared to control MT. The total number of osteons in the mid-diaphysis of HFS MT decreased, but tibial and MT porosities did not change with the HFS diet. Our results suggest that the deleterious effects of the HFS diet may be more related to changes in the material properties of the cortical bone rather than to osteoporotic changes in the bone. PMID- 2257527 TI - The national coaching certification program: objectives and reality. PMID- 2257526 TI - Vascular canals in bovine cortical bone studied by corrosion casting. AB - The architecture of vascular canals in cortical bovine bone was studied by a corrosion casting method. Prior to perfusion of the casting polymer, both cellular and nonmineralized components were removed to ensure proper impregnation into vascular canals--haversian and Volkmann's canals within secondary osteons and the vascular canals of periosteal circumferential lamellae. The resulting castings revealed an anastomotic system of canals within and between these two regions of cortical bone. The nature of these arborizations, their varying degrees of interconnectiveness, and their spatial, three-dimensional ordering are clearly demonstrated in this study. PMID- 2257528 TI - The need for sport-specific tests. PMID- 2257529 TI - Meeting carbohydrate and fluid needs in soccer. AB - If a hard game of soccer is played under warm conditions, there are conflicting demands for carbohydrate and for fluid replenishment, with both variables having a potential influence upon competitive performance. The present review examines evidence concerning the extent of carbohydrate depletion during soccer play, its potential impact upon play, and the optimum choice of beverage for minimizing physiological problems. Players should be prepared for competition by eating a good mixed diet; this should assure a daily intake of at least 8 g of carbohydrate per kilogram of body mass. Although theoretical arguments favour the use of glucose/polymer drinks, in practice, these do not offer any great advantage relative to water or a dilute glucose solution. Some 500 mL of water or a low-concentration carbohydrate preparation can usefully be drunk in the thirty minutes immediately prior to a game, with a further 500 mL drink of the same fluid being taken at half time. During the recovery period following a soccer match, it is useful to increase the salt content of meals, and again to provide a good mixed diet with an emphasis upon carbohydrates. PMID- 2257530 TI - Bioelectric impedance methods for the estimation of body composition. AB - The present use of bioelectric impedance is based upon the greater electrolyte content and conductivity of fat-free mass (FFM). The limitation of the whole body impedance approach may be the use of S2/R as an index of the conductive volume of the body. The use of body lengths that closely resemble the actual length of the conductor rather than stature can improve predictions of FFM. Theoretically, the specific resistivity approach to bioelectric impedance also provides a means of circumventing this problem. Another alternative is the estimation of whole body composition or the composition of body segments from measurements of the lengths and resistances of the segments and the use of the phase angle of the whole body and or body segments. Possible alternative methods for the use of bioelectric impedance would be the measurement of the composition of body segments, the determination of specific resistivities so that estimates of FFM can be calculated without the need for regression equations and the determination of the use of different current frequencies in measuring body composition with bioelectric impedance. PMID- 2257531 TI - Lower extremity preference and knee extensor torques in intercollegiate soccer players. AB - The purpose of this study was to determine whether lower extremity preference influenced the relationship between the dominant and nondominant knee extensors of intercollegiate soccer players. Twelve recreational athletes and 12 soccer players completed isometric contractions at 60 degrees flexion, and concentric eccentric contraction cycles at angular velocities of 60 degrees and 180 degrees/s through a range of motion from 90 degrees to 10 degrees knee flexion. Although the soccer players demonstrated greater peak and average torques, and greater differences between their dominant and nondominant legs, they responded similarly to recreational athletes during isometric, concentric and eccentric contractions and produced similar torque-velocity patterns. The concentric/eccentric ratios were similar for both legs and both groups, and decreased as angular velocity increased. The nondominant/dominant ratios of the soccer players, however, were significantly lower than those of the recreational athletes when calculated using peak torque (p less than .02) and nearly so when calculated using average torque (p less than .08). Nondominant/dominant ratios were not affected by the type of contraction or by the angular velocity. Further study is required to determine whether the small asymmetry (about 7%) in knee extensor strength of the soccer players is significant with respect to performance or injury rates, or may be inconsequential. PMID- 2257532 TI - Personal investment predictors of adolescent motivational orientation toward exercise. AB - The primary purpose of this study was to determine the relationship between the psychosocial components of Personal Investment Theory and exercise behavior among 237 adolescents. Specifically, the adolescents' personal incentives for exercise, perceptions of sense of self, and perceived options for exercise were examined as predictors of physical activity level. A secondary purpose was to determine the interdependence between the components reflecting personal investment and self reported exercise behavior separately by gender and activity level. Multiple regression analysis revealed that the personal investment variables accounted for 19% of the variance in exercise behavior among male adolescents and 25% of the variance in exercise behavior among female adolescents. Discriminant analysis correctly classified 76.5% of the males and 71.8% of the females as well as 80.4% of high-active adolescents and 73.3% of low-active adolescents on the basis of the three meaning components. Further, the results indicated that the significant predictors of exercise behavior varied as a function of gender as well as the adolescents' level of physical activity. PMID- 2257533 TI - Study of decision-making in squash competition: a computer simulation approach. AB - This paper describes how a computer simulation approach was used to specify some of the cognitive processes underlying decision-making in squash competition. The work presented in this article focused on the cognitive strategy of the defending player when choosing among three categories of preparation. (Total preparation for one particular event, partial preparation in favor of one event, and absence of biased preparation.) The defending player is viewed as in information processing system (IPS) placed in a problem-solving situation, the problem being what decision to reach. There are four steps inherent to the computer simulation approach: (a) obtaining the verbal protocol, (2) analyzing the protocol, (3) computer simulation, and (4) validation. This paper describes how each of those steps have been completed, with a special emphasis being placed on the first step of the procedure, that of obtaining the verbal protocol. PMID- 2257534 TI - Expert assessment of the national coaching certification program (NCCP) theory component. AB - The purpose of this study was to determine if the educational objectives of the revised national coaching certification theory program (NCCP) represent the important and necessary skills needed to be an effective coach in both contemporary and future Canadian society. A study sample of experts in coach education in Canada (n = 75) agreed to participate in the investigation which was based on a research protocol known as the Delphi technique. Results of the study indicate that coach education experts in Canada generally agreed with the educational objectives at each level of the program in both the present and the futures data. Further, the experts seemed to favour a socio-psychological orientation to the curriculum content at level 1 and level 2 and a balance between the biophysical and the socio-psychological sports science areas at level 3. PMID- 2257535 TI - Physiologic response of nordic ski racers to three modes of sport specific exercise. AB - This study compared the response of cross-country skiers to 3 modes of sport specific exercise. Eight racers completed 2 treadmill tests: ski-walking, and ski walking with arm resistance provided by a pulley system, as well as a simulated skiing test. Although the average time to exhaustion was significantly less for the skimill test than for the other tests, there were no differences in the maximal responses to exercise. Heart rate, blood lactate, oxygen uptake, minute ventilation and breathing frequency were all significantly greater during the submaximal stages of the skimill test than during the 2 treadmill tests. Anaerobic threshold did not differ between the 2 treadmill tests; however, the addition of arm work significantly delayed its occurrence. Arm pulleys may not increase the specificity of, or add additional work to, a ski-walking test, but rather decrease the demand placed on the athlete by supporting body weight as elevation is increased. PMID- 2257536 TI - Bronchiolo-alveolar regions in adenocarcinoma arising from canine segmental bronchus. AB - Adenocarcinomas induced in canine bronchial segments placed subcutaneously have bronchiolo-alveolar regions. Immunocytochemistry and routine staining of adjacent sections strongly suggests that the lining of these regions consists of type II cells. These regions may thus represent true prospective alveolar regions, as also seen in embryonic lungs. This first observation of bronchoalveolar cancer arising from a major bronchus indicates that the carcinogen-induced neoplastic progression in bronchial epithelium may lead to type II cell differentiation and type II cell tumor development. The preservation of cell properties in serial nude mouse transplants suggests that it is a stable type II cell population. PMID- 2257537 TI - Rectal epithelial proliferation in women recovered from breast cancer. AB - Women recovered from breast cancer are at increased risk for colorectal neoplasia. The reasons may be genetic, dietary or endogenous hormonal risk factors. Measurements of rectal epithelial proliferation are a useful biomarker of risk for large bowel cancer. This was studied in 12 women after (mean 7.8 years) cured breast cancer, who had a mean % labelling index of 7.5 +/- 3.5 (S.D.) as compared to 5.8 +/- 1.8 (S.D.) in a disease-free comparison group of 25 women. In addition, analysis of labelled crypt compartments demonstrated a significantly higher proportion in the study group with thymidine uptake, mainly in the mid crypt zone, and an extension of crypt cell DNA synthesis towards the surface epithelium. Using proliferative activity as a biomarker of risk in a larger study group, we may learn more about common etiological factors for both malignancies and also identify a higher-risk subgroup for long-term follow-up and possible therapeutic intervention. PMID- 2257538 TI - Base sequences of highly repetitive components in nuclear DNAs from rat liver and rat-ascites hepatoma. AB - A 370-bp highly repetitive component in each of the nuclear DNAs from rat liver (RL) and rat-ascites hepatoma (AH) was isolated by HindIII digestion and cloned in pUC9. Ten of the resulting clones were arbitrarily selected and sequenced. Heterogeneity of size was found in 7 of the RL clones (366-369 bp), but in only 2 of the AH clones (369 bp). The sequence homology was 64.6% among the RL clones; 80.3% among the AH clones. The base compositions were AT-rich, ranging from 61.1% to 64.7%. Many A and/or T runs consisting of 2-5 bases were interspersed throughout each sequence. The restriction sites reported previously, EcoRI, HaeIII, HindIII, HinfI and HphI sites, were confirmed in almost all of the clones. In the present experiment, 12 kinds of the sites were further found in both RL and AH clones. PMID- 2257539 TI - Solasodine glycosides. In vitro preferential cytotoxicity for human cancer cells. AB - Solamargine [(22R,25R)-spiro-5-en-3 beta-yl-alpha-L-rhamnopyranosyl- (1----2glu) O-alpha-L-rhamnopyranozyl (1----4glu)-beta-D-glucopyranoze], a glycoside of solasodine preferentially inhibits the uptake of tritiated thymidine by cancer cells. In contrast, solamargine at equivalent concentration, and the mono- and diglycosides of solasodine have a limited effect on the uptake of tritiated thymidine for other cell types, including unstimulated lymphocytes and lymphocytes stimulated with Con A. In contrast the solasodine glycosides do not inhibit the uptake of tritiated thymidine by lymphocytes stimulated with PHA or PWM. The inhibition of tritiated thymidine uptake by solamargine and the mono- and di-glycosides of solasodine are dependent upon their cellular uptake by endogenous endocytic lectins (EELs). The mode of action of the solasodine glycosides, in particular solamargine, appears to be the induction of cell lysis, as determined by morphological examination. PMID- 2257540 TI - Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180. AB - BEC, a standard mixture of solasodine glycosides is effective in vivo against murine sarcoma 180 (S180), whereas the aglycone solasodine at equimolar concentrations is ineffective. The efficacy of BEC against S180 in vivo can be inhibited by rhamnose. Mice which are in their terminal stage with S180 can tolerate and become symptom-free of cancer by single dose administration of BEC at concentrations of BEC three times the LD100 for normal mice. These observations suggest that the binding of solasodine glycosides on tumour cells may be mediated through the monosaccharide rhamnose, which forms part of solasonine, solamargine and di-glycosides of solasodine in BEC. Furthermore, these results provide evidence that BEC selectively destroys tumour cells relative to normal cells in vivo. PMID- 2257541 TI - Increased multiplicity of lung adenomas in five generations of mice treated with benz(a)pyrene when pregnant. AB - The effect of benz(a)pyrene (BP) given to female mice of A strain on the 18 and 19th days of pregnancy was studied in 5 consecutive generations. As expected there was a high incidence of lung tumours (TBA%) in the F1-generation of mice treated with BP (53.9 vs. 15.4% in control in females and 77.6 vs. 8.0% in control in males). The percentage of TBA was not increased (with one exception) in both males and females of F2-F5 generations which were not directly exposed to carcinogen. Tumor multiplicity increase occurred not only in the F1 generation of BP-treated mice but in both males and females of F2-F5 generations of mice which were not in direct contact with the carcinogen. This increase was statistically significant. There was a slight negative trend within F2-F5 generation of BP treated mice which however was not significant. Thus the transgenerational carcinogenic effect manifested in a greater tumour multiplicity persisted for four unexposed generations. PMID- 2257543 TI - Variant Philadelphia translocations in chronic myeloid leukemia: correlation with cancer breakpoints, fragile sites and oncogenes. AB - Four cases of variant Philadelphia (Ph1) translocations were found in 72 patients (5.5%) with Ph1-positive chronic myeloid leukemia (CML). One previously unreported case was a simple variant translocation, namely, 46,XY,t(11;17)(q13;p13),t(17;22)(q25;q22); 46,XY,t(1;21)(q32;q11),t(11;17)(q13;p13), t(17;22)(q25;q11). Complex variant translocations were observed in three cases, namely, 46,XY,t(5;9;22)(q31;q34;q11),46,XX,t(8;9;22) (q22;q34;q11) and 46,XX,t(9;15;22) (q34;q15;q11). The chromosomal breakpoints in the cases of variant Ph1 translocations were the following: 1q32, 5q31, 8q22, 11q13, 15q15, 17p13, 17q25 and 21q11. Eight of the eight (100%) breakpoints were located in Giemsa-negative bands. Furthermore, seven of the eight (87%) variant Ph1 breakpoints correspond to the breakpoints present in consistent cancer arrangements. Three of the eight (38%) correspond to fragile sites and four of the eight (50%) correspond to oncogenes. PMID- 2257542 TI - Azaserine-induced pancreatic carcinogenesis in rats: promotion by a diet rich in saturated fat and inhibition by a standard laboratory chow. AB - Dietary fat has been shown to enhance pancreatic carcinogenesis. Uncertainty still exists whether the amount of linoleic acid or the amount of fat is the main determining factor. In the present study the effects of a high lard, a low lard, a linoleic acid supplemented low lard and a laboratory chow diet were investigated on the development of (pre)neoplastic pancreatic lesions in rats treated with azaserine. The rats were killed 15 months after carcinogen treatment and the pancreata were examined for the number and size of putative preneoplastic lesions and for the occurrence of neoplasms. The linoleic acid supplemented low lard group showed a significantly increased number of basophilic foci as compared to the low lard group. Rats maintained on the linoleic acid supplemented diet or the laboratory chow developed significantly less atypical acinar cell nodules larger than 1.0 mm in diameter and adenocarcinomas as compared to the high lard group. Animals maintained on the low lard diet developed significantly less adenocarcinomas than rats on the high lard diet did. Overall, the number of benign and malignant pancreatic tumours was consistently higher in the high lard group and consistently lower in the linoleic acid supplemented low lard group than the number of these types of tumours in the low lard group, with the exception of the number of carcinomas in situ, which was lower in the high lard group. The laboratory chow group showed a significant lower number of atypical acinar cell nodules with a diameter over 1.0 mm and a lower number of adenocarcinomas as compared to both the high lard and the low lard group. It is concluded that a diet high in saturated fat has a promoting and that laboratory chow has an inhibitory effect on pancreatic carcinogenesis in azaserine-treated rats. PMID- 2257544 TI - Neurosurgery with craniotomy and CT stereotactic guidance in the treatment of intracerebral space-occupying lesions. AB - When intracerebral space-occupying lesions are small or located deeply within the brain parenchyma, it is sometimes difficult to localize them at surgery or to design the most direct and least hazardous surgical approach. Therefore, we have developed a method that combines conventional neurosurgical techniques with craniotomy using stereotactic guidance. We have used the Brown-Roberts-Wells (BRW) stereotactic system, which allows for computed tomography (CT) or magnetic resonance imaging (MRI) guidance and does not interfere with the absolute sterility mandatory each time a flap is created. Eleven patients were operated on using this method. The deep tumors were approached through a linear incision of the cerebral cortex. Then a needle, fixed in the right position on the arc system of the BRW, was inserted toward the surface of the lesion; the exposure was finally widened by inflation of a rubber balloon set on the stereotactic needle. This technique allows the two lips of the cortical incision to be glued at the end of the operation. Gluing with a fibrin glue avoids the postoperative subdural collections that often develop when the ventricle has been opened. Except for one case, the postoperative course was uncomplicated in these patients. No permanent postoperative neurological worsening was observed even after the removal of an intrathalamic tumor. PMID- 2257545 TI - Has modern management improved the outcome of infants with intracranial tumors? AB - Records of 92 children were reviewed who, in the first 18 months of life had an intracranial tumour, and who were registered with the Manchester Children's Tumour Registry during the 34-year period from 1953 to 1987. The incidence of intracranial tumour was 1 in 25,000 live births, and 85% of the tumours were malignant. The introduction of computed tomography (CT) in the region in 1976 improved the diagnostic accuracy and led to early diagnosis. This also coincided with refined radiotherapy and improved chemotherapy. The surgical attitude became more aggressive, and with early treatment, mortality was reduced, though the 1 month operative mortality still remains high at 15%. All survivors were available for follow-up. All children with axial tumours died within 9 years. Long-term follow-up did not suggest significant improvement in the overall survival or in the quality of life, though there was a significant improvement in the 5-year survival rate with modern management. PMID- 2257546 TI - Choroid plexus papillomas of the III ventricle in childhood. Their diagnosis and surgical management. AB - Ten infants and children with choroid plexus papilloma of the III ventricle are presented. Hydrocephalus of various degrees was present in all patients, and seven patients had bilateral ventriculoperitoneal shunts prior to craniotomy. All patients were investigated with computed tomography and angiography. Tumor was resected through the transfrontal-transventricular approach in nine and through a transcallosal approach in one. One patient died intraoperatively due to an uncontrollable hemorrhage from a subependymal vein at its point of entry into the homolateral internal cerebral vein, and another died shortly after surgery due to hypothalamic trauma. The remaining eight patients are alive without recurrence over a minimum follow-up period of 3 years; three have mental retardation and seizure disorder. Despite this tumor's deep location and vascularity and occurrence in infancy, choroid plexus papillomas of the III ventricle can be successfully resected. Appropriate care for hydrocephalus and intra- and postoperative management are important. PMID- 2257547 TI - Dandy-Walker syndrome: posterior fossa craniectomy and cyst fenestration after several shunt revisions. AB - Ventriculoperitoneal or cyst-peritoneal shunts are the usual treatment for children with Dandy-Walker syndrome. A combined ventricular and cyst shunt is often necessary and, in some cases, multiple revisions have to be done. Two patients with this syndrome were treated with posterior fossa exploration and cyst fenestration after several shunt revisions. The procedure was well tolerated with good results in both cases. The patients' data and preliminary results are presented here. PMID- 2257548 TI - Pathophysiology and postnatal outcome of fetal hydrocephalus. AB - At the National Kagawa Children's or Kobe University Hospital, 24 cases of fetal hydrocephalus were managed between 1982 and 1988. There were 8 simple, 11 dysgenetic, and 5 secondary cases of hydrocephalus, and the fetal age at diagnosis ranged between 24 and 40 weeks of gestation (average 33.4 weeks). All were diagnosed using ultrasonography, with either magnetic resonance imaging or whole-body computed tomography, additionally performed in 10 patients to determine their usefulness in evaluating the morphology. Four patients underwent transabdominal or transvaginal cephalocentesis in the prenatal period and intracranial pressure was measured during the drainage of cerebrospinal fluid in two of these. Postnatal outcome was analyzed for each type of hydrocephalus. The results suggested that in such cases the fetal brain is subjected to extremely high intracranial pressures resulting from a mixture of hydrocephalic pressure and intermittent uterine constriction. Immediately after birth, the biparietal diameter was found to be increased by an average of 7.7 mm and the hydrocephalic state was transformed into the neonatal type characterized by macrocephaly and a relatively low intracranial pressure. Overall mortality was 25% and 16 of the 24 infants underwent the postnatal shunt procedure, largely at the neonatal stage. The follow-up period varied from 4 months to 6 years (average, 25.8 months for nonfatal cases) and the mean intelligence or developmental quotient was 45.2. There were no significant differences in postnatal outcome between the three major types of fetal hydrocephalus. Findings revealed that the length of the gestation period after the diagnosis of hydrocephalus has a significant effect on outcome (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257549 TI - Avoidable factors that contribute to the complications of ventriculoperitoneal shunt in childhood hydrocephalus. AB - A personal series of 80 consecutive children who underwent ventriculoperitoneal shunting for hydrocephalus has been followed up for a period of from 6 months to 6.5 years. Complications occurred in 8 patients; these included partial occlusion of the ventricular catheter in 2, infection in 2, peritoneal catheter-valve disconnection with migration of the catheter into the peritoneal cavity in 2, fracture of the peritoneal catheter just below the valve in 1, and failure of the peritoneal cavity to absorb cerebrospinal fluid in another. Analysis of the results in the present series showed that the complications result from the technique. The operative procedures responsible for a low complication rate in the present series are described. It is concluded that to avoid shunt complications, attention must be paid to the following factors: meticulous asepsis; good surgical technique, including testing of the shunt system to make certain that the correct opening pressure is present; elimination of contact between the shunt system and the patient's skin; placement of the valve under a pericranial flap; positioning the tip of the ventricular catheter just in front of the foramen of Monro and that of the peritoneal catheter in the pelvic peritoneal cavity. PMID- 2257550 TI - Morphological evaluation for neuronal maturation in anencephaly and encephalocele in human neonates. A proposal of reclassification of cephalic dysraphism. AB - The developmental pathogenesis of cranium bifidum and exencephaly, as well as other forms of the dysraphic state, remains unresolved. The process of neuronal maturation under such conditions is the major definitive factor for functional prognosis and may be the key to the embryopathogenesis. The neuronal maturation processes in cranium bifidum and anencephaly were analyzed in both human neonatal autopsy and surgical specimens, utilizing the technique of immunohistochemical morphological analysis. The results suggest that anencephaly is a form of neuroschisis, a defect in which the neuronal developmental process arrests and results in dys- or rather aplastic cortical architecture. In contrast, although the cortical architecture is often distorted, neuronal maturation in cases of cranium bifidum cysticum is primarily complete, demonstrating normal cerebral cortical layers and NSE positive neural elements. In conclusion, it is strongly suggested that anencephaly is the most severe form of cranium bifidum, as is myeloschisis in spina bifida, without supportable neuronal maturation. Recognizing these points in the developmental stages with regard to the degree of neuronal maturation, a reclassification of cephalic dysraphism is proposed. The embryopathogenetic and epidemiologic aspects of this proposal of reclassification are discussed. PMID- 2257551 TI - Vascular anomalies of the scalp. AB - Paediatricians and surgeons of different disciplines are referred vascular anomalies of the scalp from time to time. These rare lesions may produce serious side-effects and the authors review the treatment of these abnormalities illustrated by five cases. Where possible, total excision is the treatment of choice. PMID- 2257552 TI - Traumatic intracavernous aneurysm in children: massive epistaxis without ophthalmic signs. AB - Traumatic intracavernous aneurysms are a distinctly uncommon lesion in children. They usually present with compressive symptoms of the III, IV, V, or VI cranial nerves rather than epistaxis. Epistaxis is rare and usually minor and brief in duration. A child with severe head injury and basal skull fracture, who did not have any preceding symptoms or signs of ophthalmoplegia or exophthalmus, developed massive epistaxis as a leading symptom of the ruptured intracavernous aneurysm. Since there are no reported pediatric cases with fatal epistaxis as a presenting sign, we would like to share our experience. PMID- 2257553 TI - A case of intraventricular arachnoid cyst. How should it be treated? AB - A rare case of arachnoid cyst in the trigone of a lateral ventricle is reported. The patient was an 8-year-old boy who had had four episodes of convulsions prior to admission. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a cystic lesion containing fluid resembling cerebrospinal fluid. Although he received a cyst-peritoneal shunt, the lesion did not decrease in size. Direct removal of the cyst was then scheduled. The entire cyst was finally removed, although it was firmly attached to the choroid plexus. The enlarged trigone gradually decreased in postoperative CT. The effectiveness of a cyst peritoneal shunt is not always satisfactory. We recommend total resection of the cyst without use of a shunt system. PMID- 2257554 TI - Pituitary tooth: case report of a suprasellar teratoma. AB - A rare case of intracranial teratoma is reported in which a tooth-like structure was clearly defined in the pituitary fossa. The authors are unaware of any similar case having been reported previously. PMID- 2257555 TI - Lifestyle: an overview. AB - Lifestyle is a convenient portmanteau term which, in relation to the causes of cancer, has come to mean all aspects of the way people behave, whether determined voluntarily or imposed by economic, cultural, or geographic circumstances, including reproduction but arbitrarily excluding occupation. Modification of lifestyle seems to be able to reduce the age-specific risk of cancer by about four fifths in many communities. This does not imply that the control of other factors could not reduce the risk by more than a fifth, as the chain of causation can be broken in many places and the occurrence of any one case of cancer could be avoided in several different ways. Examples are given of the way different aspects of lifestyle interact, and particular attention is paid to the consumption of ethanol which has a major impact on the incidence of human cancer, although it does not appear to be a carcinogen in animal experiments. PMID- 2257556 TI - Reducing cancer risk in women through lifestyle-mediated changes in hormone levels. AB - The major hormone-associated cancers of women, viz. breast, endometrium, and ovary, account for some 40% of all female cancers in the U. S. Variable expression of estrogens and progestins account for major differences in the incidence of breast and endometrial cancer. Identified differences in premenopausal ovarian hormone expression and the known effects of post-menopausal weight on estrogen metabolism now permit an essentially complete hormonal explanation of the epidemiology of endometrial cancer. Recent confirmation of decreased ovarian steroid levels in certain Oriental women now permits a hormonal explanation of the four- to sixfold differences in breast cancer rates between Japanese and U.S. women, and a complete hormonal explanation of the epidemiology of breast cancer is almost at hand. A delay of 2 years in the age at menarche plus a low postmenopausal weight are predicted to lead to a more than 50% lifelong reduction in both breast cancer and endometrial cancer. A 2-year delay in menarche is predicted to lead to an 18% reduction in ovarian cancer. The lifestyle basis of variable premenopausal ovarian hormone expression is poorly understood and should be the focus of a major research effort. Profound effects on estrogen and progestin expression and on cancer rates are obtained from use of hormonal contraceptives and menopausal hormone replacement therapy; it appears possible to use this knowledge to construct a LHRHA-plus-estrogen contraceptive regimen that should produce a major lifelong reduction in current U.S. breast cancer rates (32% reduction from 5 years use; 55% from 10 years use). The proposed regimen should also cause a major lifelong reduction in ovarian cancer rates (40% reduction from 5 years use; 66% from 10 years use). Addition of a progestin-containing IUCD to such a regimen should also cause a major lifelong reduction in endometrial cancer rates (55% reduction from 5 years use; 82% reduction from 10 years use). PMID- 2257558 TI - Hematopoietic growth factors in oncology. AB - Hematopoietic growth factors, or hemopoietins, are peptide hormones produced by peripheral blood cells, bone marrow stroma, as well as several other cell types, such as endothelial cells and fibroblasts. Hemopoietins play a central role in regulating peripheral blood cell number and function. By recombinant DNA technology, several of these factors, also called colony-stimulating factors (CSF) or interleukins, are now available in such quantities to allow clinical evaluation. First experiences in clinical trials show that these peptides are capable of stimulating production of various cell types of the peripheral blood by stimulation of bone marrow progenitor cells without significant toxicity for the patient under treatment. Treatment of renal anemia by erythropoietin and reduction of chemotherapy-induced myelosuppression by G- and GM-CSF are already defined indications for these hemopoietins. Further studies are under way to test the indication of these factors in other clinical situations as well as studies investigating the biology, pharmacology, and clinical efficacy of interleukin 3 (IL-3). PMID- 2257557 TI - Immunobiology of aging and cancer. AB - Although the incidence of neoplasms is increased in the elderly, some tumors appear to grow more slowly in old as compared to young patients. We have used the B16 melanoma to explore the relationship between age, T-lymphocyte function, and the rate of tumor growth. Increasing age is associated with a decreased rate of tumor growth and impaired T-cell function in C57BL/6 mice. Furthermore, when T cell immunity in young mice is compromised by thymectomy, B16 tumor growth is decreased. Mixed cell transfer studies demonstrated that T cells from young but not old donors stimulate the growth of B16 melanoma cells in young lethally irradiated recipients. Recently, T cells from young but not old mice have been reported to produce angiogenic factors. As tumors from young mice have a richer vascular supply than in old mice, it appears that one mechanism for the age associated decrease in B16 melanoma growth is the decreased capacity of T cells from old mice to generate angiogenic factors. However, parabiosis of young and old mice showed that local factors in old mice also limit the stimulatory influences of T cells from young mice. Novel therapeutic approaches to limit the growth of tumors might result from a greater understanding of the production of and response to angiogenic factors produced by T cells. PMID- 2257559 TI - The role of cigarette smoking and drinking in the development of liver cancer: 28 years of observations on male cohort members in a farming and fishing area. AB - Cohort studies of 639 males in a farming area (Cohort I) and 677 males in a fishing area (Cohort II) in Kyushu, Japan, had been conducted to assess the involvement of smoking and drinking in the development of liver cancer. An observed-to-expected (O/E) ratio of liver cancer was 1.3 in Cohort I and 3.1 (p less than 0.01) in Cohort II. A significant excess in deaths was found in Cohort II. No significant risk elevation was observed for smokers and drinkers in Cohort I. Although the odds ratio (OR) of 3.6 (0.6 to 22.3) suggested an elevated risk among cigarette smokers in Cohort II, no clear linear trend of ORs was observed. In contrast, a significant elevation of OR (7.0) was noted among shochu drinkers in this cohort. The respective ORs were 5.0 (1.3 to 19.7), 8.6 (2.1 to 36.1), 14.1 (3.6 to 55.9) for shochu drinkers of less than 1, 1 to 2, and 2+ units (approximately 180 ml in volume), and a highly significant dose-response relationship was observed (chi 2 = 12.1; p less than 0.001). Multiple logistic regression analysis indicated an insignificant effect of smoking and a major contribution of drinking to the development of liver cancer. Shochu drinking (or probably high alcohol intake) seems to have a significant involvement in the etiology of liver cancer, at least in Cohort II. PMID- 2257560 TI - Geographic patterns and trends in the incidence of thyroid cancer in Norway 1970 1986. AB - Norway has a special geographic distribution of thyroid cancer. There are very high incidence rates in the most northern part and an average Scandinavian level in the south. The incidence began to decline in the 1980s after increasing for a long time. The decline affects females more than males and is mainly seen in the oldest age groups and in mid- and north Norway. The decline is in papillary carcinomas and stage 1 and has occurred in primary trade communities more than the others. Cohort analysis demonstrates a secular trend in females, a continuous risk shift from older to younger age groups as the cohorts become younger--which explains the current bimodular age-specific incidence curve. Etiologic aspects are discussed. PMID- 2257561 TI - Cancer control research for community programs: the National Cancer Institute initiative. AB - Recognizing the need to integrate community populations into cancer control research and building on the demonstrated success of community oncologists to participate in treatment clinical trials, the Division of Cancer Prevention and Control, NCI, expanded the focus of the Community Clinical Oncology Program in 1987 to foster the development and implementation of cancer control research through the existing clinical trials network. NCI-funded cooperative groups, cancer centers, and a state health department provide research opportunities in screening and early detection, chemoprevention, smoking cessation, and continuing care. Feasibility protocols, pilot studies, and randomized clinical trials are in progress. This effort links community oncologists and other health care professionals to research in cancer control; provides access to large populations for preventive oncology studies; and establishes an effector arm for transferring current knowledge into community practices. The CCOP program is a model for maximizing available resources for future cancer control research and public health measures. PMID- 2257563 TI - Risk factors in asymptomatic subjects screened for colorectal cancer. AB - The purpose of this study was to determine the importance of risk factors in 531 asymptomatic voluntary subjects screened for colorectal benign polyps and malignancy. Age limits were 50 years or above. A questionnaire was completed by all subjects with the results reviewed by a physician who checked for correct interpretation and accuracy of their responses. High risk factors in this study were current colorectal adenomatous polyps and malignancies, positive fecal occult blood test (FOBT), past history of colorectal benign polyps or malignancies, family medical history of first and second degree relatives with benign polyps or malignancies, multiple malignancies in the family, and ulcerative colitis. There were 531 60-cm flexible fiberoptic sigmoidoscopies (FFS), 330 FOBT, and 97 (18.3%) colonoscopies performed. A total of 139 (26%) subjects had one or more high risk factors, and among these subjects, 69 (13%) adenomatous polyps, 2 (0.38%) malignant polyps, and 1 (0.19%) invasive adenocarcinoma were found. Subjects known to have high risk factors, including those who are asymptomatic, should be screened for colorectal polyps and malignancies. PMID- 2257562 TI - Molecular epidemiology and cancer prevention. AB - A review of recent studies of biologic markers in populations with model exposures to carcinogens (cigarette smoke and polycyclic aromatic hydrocarbons) illustrates their potential role in cancer prevention. Data on macromolecular adducts and oncogene activation from cross-sectional, serial sampling and case control studies demonstrate the usefulness of biologic markers in signalling a potential carcinogenic risk and in estimating the magnitude of interindividual variation within exposed groups. Recommendations for future research include nested case-control studies to establish the relationship between markers of biologic dose and effect (e.g., adducts, gene mutation, oncogene activation) and cancer risk. PMID- 2257564 TI - Radioimmunoguided surgery in primary colon cancer. AB - Radioimmunoguided surgery (RIGS), the intraoperative use of a hand-held gamma detecting probe (GDP) to identify tissue containing radiolabeled monoclonal antibody (MAb), was performed upon 30 patients with primary colon carcinoma. Each patient received an intravenous injection of MAb B72.3 (1.0 to 0.25 mg) radiolabeled with 125I (5.0 to 1.0 mCi) 8 to 34 days before exploration. The GDP was used to measure radioactivity in colon tissue, tumor bed, nodal drainage areas, and areas of suspected metastases. Antibody localized to histologically documented tumor in 23 of 30 patients (77%). Tumor margins were more clearly defined in 20 of 30 patients (67%). GDP counts led to major alterations in surgical resection in five patients (17%) and changes in adjuvant therapy in four (14%). GDP counts identified occult liver metastases in two patients (7%) and correctly indicated the benign nature of liver masses in three (10%). In four patients (13%), occult nodal metastases were identified. RIGS can precisely delineate tumor margins, define the extent of nodal involvement, and localize occult tumor, providing a method of immediate intraoperative staging that may lessen recurrences and produce higher survival rates. PMID- 2257565 TI - Problems and prospects of new immunotherapeutic approaches. AB - Active immunotherapy of cancer is based on the hyperactivation of the immune system of tumor-bearing patients. Interleukin 2 (IL2) has proven to be the most potent immunostimulant used so far. Therapeutic activity of IL2 and IL2-activated lymphocytes has been reported in the treatment of certain tumors such as metastatic melanoma and renal carcinoma. Effectiveness is related to the dose of IL2 administered to the patients, as are important toxic effects. Other cytokines, such as interferon (IFN) and tumor necrosis factor (TNF), are used for their direct effect on malignant cells, particularly those of the lymphoid lineage. The development of these new immunotherapeutic approaches will depend on the quality of their scientific bases, the clinical follow-up of the toxic effects, and the social management of the costs. PMID- 2257566 TI - Recent trends in allogeneic bone marrow transplantation. AB - The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute non lymphoblastic leukemia in first complete remission (CR), the disease-free survival (DFS) is 45%, with a risk of relapse (RR) of 15%; in ALL in first CR the DFS is 60% with a RR of 15%; in ALL in second CR the DFS in 40%, with a RR of 30%; in CML in chronic phase the DFS is 60%, with a RR of 20%. These results have to be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GVH. The use of donors different from a genotypically matched related donor is currently under investigation. Mismatched related transplants give disappointing results except in the case of one HLA mismatch. Unrelated HLA matched donor panels have been recently established in various countries with 200 transplants performed with a DFS of approximately 40%. Current research tries to reduce the risk of relapse by intensifying the conditioning or using the GVL effect of allogeneic T cells, to reduce GVH by the use of monoclonal antibodies and to improve the engraftment by the use of growth factors. PMID- 2257567 TI - [Primary geriatric care]. AB - Geriatric patients account for some 60% of the patients who se their health community doctor who thus is also the geriatrician of the first line. According to experience from abroad (Sweden) it is assumed that general practitioners will take over the medical and social care of aged subjects. The authors describe activities associated with this role. They draw attention to the hitherto inadequate collaboration of doctors with the patients' families. PMID- 2257568 TI - [Interrelation between static parameters of trabecular bones in acromegaly, the STH levels and the duration of the condition. Histomorphometric study]. AB - To evaluate trabecular bone formations of active acromegalic patients the authors used the method of histomorphometry and correlated the calculated variables of the trabecular volume (V), osteoid volume (Vos), osteoid surface (Sf) and width of the osseous trabeculum (MTT) with STH levels, the patients' age and the period of the acromegalic process. No correlations were found between Vos, Sf, MTT and STH levels, age and the length of the case-history. There were negative correlations (p less than 0.05) between the trabecular volume (V) and the period of the case-history and trabecular volume (V) and the patients' age. From the results it may be concluded that STH does not influence the balance between resorption and formation of the acromegalic spongiosa in favour of formation. PMID- 2257569 TI - [Effectiveness of replacement of renal function in diabetics]. AB - The authors compared the survival of four groups of patients and of renal grafts: 1. diabetics after renal transplantation (24 subjects), 2. diabetics after transplantation of the kidney and pancreas (35 subjects), 3. diabetics where transplantation was indicated but who were treated only by dialysis and 4. non diabetics after transplantation of the kidney (170 subjects). The two-year cumulative survival of the entire group of diabetics regardless of the type of treatment was 59%. The two-year survival of diabetics after transplantation of the kidney alone was 95%, after transplantation of the kidney and pancreas 70% and in non-diabetics after transplantation of the kidney 90%. In diabetics treated by dialysis it was 33%. The two-year survival of the function of renal grafts in the entire group of diabetics treated by transplantation of the kidney was 61%, in non-diabetics 68% and the three-year survival was in both groups 61%. As compared with the EDTA register, the results of transplantation treatment are favourable, the results of dialyzation treatment are poor. From the results the authors draw conclusions for indication of different ways of replacement of renal function in diabetics in relation to the general health status of the patients. PMID- 2257570 TI - [Recurrence of idiopathic membranous glomerulopathy]. AB - In 30 patients with idiopathic membranous glomerulopathy during prednisone treatment and prednisone and cyclophosphamide treatment resp. partial or complete clinical remission was recorded. In the course of the investigation (118 +/- 77 months) in 7 patients 1-4 relapses occurred. The relapses occurred more frequently in women. There was no difference between the two groups as regards clinical manifestations and morphological findings at the onset of the disease. All relapses were treated in the same way as the first attack. Treatment had in all patients the same result as during the first attack and in the course of the investigation in none of the patients deterioration of renal functions was recorded. In case of effective immunosuppressive treatment the prognosis of patients with relapses is not worse than in patients without relapses. PMID- 2257571 TI - [Ectodermal dysplasia with alopecia, a higher rate of chromosome breaks and normal dentition]. AB - The authors present in two case-histories of unrelated female patients the characteristics of the syndrome of ectodermal dysplasia with alopecia and absence of hair and concurrent immunodeficiency and a higher number of chromosomal breaks. In the probands some other important symptoms of ectodermal dysplasias were lacking, such as disorders of dentition and absence of sweat glands. In this affection, hitherto not mentioned in our literature in conjunction with an increased number of chromosomal breaks, the author draws attention to genetic and prenatal genetic associations. He assumes an autosomal recessive heredity of this nosological unit. PMID- 2257572 TI - [Use of cytochalasin B in the micronucleus test in human peripheral lymphocytes]. AB - The micronucleus test is one of the alternative procedures of cytogenetic analysis. Its modification with the use of cytochalasine B (Calbiochem AG) ensures safely the recording of changes of the genetic apparatus in the first cellular cycle after an attack of a mutagenic agent on human peripheral lymphocytes. The authors elaborated a reproducible modification of the original work of Fenech and Morley--published in this country by Kocisova and Sram--and describe in detail its individual steps. The cytochalasine MN-test which should become part of obligatory standard procedures of Czechoslovak preventive health services (formerly hygiene service) is thus open to confirmation. PMID- 2257573 TI - [Prevention of cardiovascular diseases in adults beginning in childhood: time to begin]. PMID- 2257574 TI - [Physician-martyrs of the Czech resistance. The most important individuals amongst the martyred physicians in the Czech resistance during World War II. II]. PMID- 2257575 TI - [Meeting of the Central Committee of the Czech Medical Society. Prague, 26 January 1990]. PMID- 2257576 TI - [The most important results of the research plan of the Ministry of Health and the Ministry of Education of the Czech Republic in 1989]. PMID- 2257577 TI - [The beginnings of local anesthesia in Czechoslovakia with special emphasis on the Caslav Hospital]. PMID- 2257578 TI - [Regulation of coronary circulation]. AB - In the submitted review the author deals with specific features of the coronary circulation, coronary reserve and importance of regulation of the tonus of the coronary arteries at their epicardiac course and the tonus at the arteriolar level. In the subsequent part the author deals systematically first with the nervous regulation incl. the basic importance of the alpha-adrenergic (vasoconstrictor) and beta-adrenergic (vaso-dilating) sympathomimetic component. He mentions also the importance of neuropeptides (neuropeptide Y and substance P). Attention is devoted to the importance of the endothelium and endothelial vasoactive substances in the control of circulation. The main representatives of substances with a vasodilatating action are the endothelial relaxation factor and prostacycline, as to vasoconstrictor substances it is endothelin, thromboxan A2 and some growth factors. The authors discuss also the mechanical component, i. e. the influence of the blood flow and viscosity on the tonus of the coronary arteries. Finally the author draws attention to the clinical importance of disorders of regulatory mechanism in atherosclerosis and some clinical entities. PMID- 2257579 TI - [Changes in the extent of residual stenosis in coronary arteries after thrombolytic therapy in acute myocardial infarct]. AB - The extent of residual coronary artery stenosis has been studied immediately after thrombolysis using streptokinase and after 3.-4. weeks follow-up in 28 patients with acute myocardial infarction. Thrombolysis was successful in 19 patients (67.9%). In these patients the extent of residual coronary artery stenosis (percentage narrowing of diameter) decreased from 73.4% to 66.1% (p less than 0.05). The residual stenosis did not change in 5 patients (26.3%), increased in 1 patient (5.2%), 3 patients suffered reocclusion of the vessel (15.8%). Marked improvement was found in 10 patients (52.6%). It means despite significant regression a coronary artery stenosis of more than 50% of diameter persisted in 47.4% of patients with successful thrombolysis 3.-4. weeks after the infarction. The factors which could be involved in regression of residual stenosis of vessel related to myocardial infarction are discussed. PMID- 2257580 TI - [Beta-sitosterol in the treatment of hypercholesterolemia]. AB - A group of 28 patients with primary hyperlipoproteinaemia [19X lipoprotein (LP) type IIA, 8X type IIB and 1X a normolipidaemic patient with concurrent hyperapoB lipoproteinaemia] were given for a period of three weeks a dietetic preparation containing phytosterols - 12 g/day. This led to a significant drop of total cholesterol and LDL-cholesterol in plasma. The cholesterol concentration in HDL and both its fractions increased, the differences however were not significant. The triglyceride levels did not change. There was a significant drop of the apolipoprotein B (apo-B) concentration in LDL, the apo-A-I in plasma did not change. There was a significant drop of atherogenic indexes TC/HDL-C, LDL-C/HDL-C and apo-B/-A-I. During investigation of the LCAT activity the authors observed a significant rise of the fractional esterification rate associated with a highly significant drop of the free cholesterol concentration in plasma as a result of treatment. Discrimination analysis of parameters of the lipoprotein metabolism and the patients' body weight before treatment helps to assess a function by means of which it is possible in 92.3% of the subjects to predict the success of treatment before the administration of beta-sitosterol. PMID- 2257581 TI - [The infundibular septum in congenital heart defects. Morphologico angiocardiographic study of the double-outlet heart ventricle]. AB - The authors investigated the infundibular septum in 40 archival heart preparations with a double outlet right ventricle. They compared the post-mortem findings with the previous angiocardiographic examination and the skiagram of the preparation made post mortem. They present also the corresponding findings obtained by echocardiography. The infundibular septum was in all instances the dominating intracardiac structure influencing the direction of the blood flow from the ventricles into outflow tracts in the direction towards the large arteries. In 15 instances the infundibular septum was shifted in an anterosuperior direction beneath the orifice of the pulmonary artery and it derived the blood current from the left ventricle through the defect in the ventricular septum into the aorta. The restricted blood flow through the aorta led to its hypoplasia, which in 11 instances was associated with coarctation or interruption of the aorta. In seven instances of posteroinferior shift the infundibular septum was straight. These cases were associated with coarctation or interruption of the aorta. In ventricular septum and with stenosis of the pulmonary artery. Based on these findings the authors assume that the shift of the infundibular septum in a double outlet right ventricle has a decisive position as regards haemodynamic manifestations of the defect and in the development of outflow tracts and large arteries. Last not least, information on the infundibular septum is also important for surgery of the defect. PMID- 2257582 TI - [Newly diagnosed diabetes mellitus in patients with focal cerebral ischemia]. AB - The authors analyze a group of 121 patients with focal cerebral ischaemia, hospitalized at the Neurological Clinic in Kosice in 1987-1989. Forty-three patients were treated before the development of the vascular attack for diabetes. In the second group of patients, comprising 78, diabetes was newly detected in 26, i. e. in one third of the group. Glycaemic compensation of 40% of the treated diabetics, evaluated on the basis of glycaemic profiles and the concentration of glycohaemoglobin, was not satisfactory. High glycohaemoglobin levels in five patients with newly detected diabetes suggested that diabetes had persisted for a long time and was probably asymptomatic. The mortality from a cerebral attack was higher in diabetics than in non-diabetics. The highest mortality was recorded in a group of women with newly detected diabetes where of nine six died. In the authors' opinion it is particularly important that in patients with newly detected diabetes death occurred at a younger age as compared with non-diabetics and with treated diabetics. Based on these results the authors confirm the view that undiagnosed and untreated diabetes is a serious risk factor for the development of focal cerebral ischaemia and that it plays moreover an important role in its subsequent course and provides a poorer perspective of recovery in the affected patients. PMID- 2257583 TI - [Prognostic significance of mediastinal involvement and post-therapeutic radiographic changes in the intrathoracic area in Hodgkin's disease]. AB - The prognostic importance of mediastinal affection and its extent was analyzed in a group of 220 patients with Hodgkin's disease in all clinical stages. The results of the total survival period in mediastinal patients are significantly worse, as compared with patients without primary affection of the mediastinum at all evaluated time intervals: in the 5th year after onset of treatment 79% vs. 95% in the 10th, 15th and 20th year 67% vs 86%, 63% vs. 86% and 56% vs. 86%. The survival of patients without a mediastinal tumour does not change after a 10-year period of follow-up, in case of a tumour mass up to 1/3 of the transverse chest diameter it declines from 81% in the 5th year to 59 and to 49% in the 10th and 15th year. In case of extensive mediastinal affection only 61% survive 5 years and 42% survive after 10 years. The differences in survival without signs of the disease are not statistically significant, obviously due to primary radiochemotherapy with alternation of cytostatic combinations. There are no significant differences in the frequency of posttherapeutic X-ray changes in the mediastinal area after primary X-ray therapy alone and after chemotherapy alone, as compared with combined radio-chemotherapy with the incidence of postirradiation changes in 30% of the patients: the incidence of post-irradiation changes is potentiated by the administration of bleomycin, depending on the dose. For evaluation of posttherapeutic X-ray changes in the area of the chest it is essential to monitor the patients by X-ray check-ups with concurrent functional examination of the lungs. PMID- 2257585 TI - [Charitable associations involved in the care of children in Ostrava]. PMID- 2257584 TI - [Peroral ciprofloxacin in the therapy of infections in oncology patients]. AB - The authors give an account of their initial experience with oral ciprofloxacin (Ciprinol) in the treatment of various infections in 28 immunosuppressed oncological patients. A favourable effect--cure and improvement--were recorded in 72% of all treated patients. Unfavourable side-effects were observed in 4 of 28 patients, in two they were the reason for discontinuation of treatment. PMID- 2257586 TI - [The systems approach and medicine]. AB - The author gives an account of the development of system thinking and modern systems science. He mentions basic terms and important names. He also draws attention to the obvious fact that it involves a new way of interpretation of phenomena of objective reality which influences in a marked way contemporary thinking. In the conclusion the author mentions the systems approach in medicine. PMID- 2257587 TI - [Results of bronchoscopy studies in patients with pleural effusion]. AB - The authors investigated in a group of 141 patients included in a study of pleural exudates at the Second Clinic for TB and Respiratory Diseases, Medical Faculty, Charles University Prague, endoscopic findings in correlation with the basic diagnosis and type of exudate. The group comprised 45 women and 96 men, mean age 52 and 54 years resp. 60.3% of the group suffered from neoplastic disease, most frequently bronchogenic carcinoma which was recorded in 56 of the patients. 114 patients were subjected to bronchoscopy, a tumour was detected by this examination in 33%, inflammatory changes in 19%, stenosis of the segments in 9% and merely dilated carinae in 3% of the subjects with pleural exudates who were subjected to bronchoscopy. The authors verified during bronchoscopy by cytological or histological examination 79% bronchogenic carcinomas, 35% other tumours. Bronchoscopy was the decisive examination; due to it the type of exudate was determined in 17 patients, i. c. 12%. In patients with other than neoplastic disease the endoscopic finding supported the basic diagnosis in 30% of the examined subjects, but did not assess the type of exudate in any of the patients. Bronchoscopy revealed pathological changes in 16 patients (11% of the group) where the skiagram of the chest indicated only changes suggesting a pleural exudate. Fifteen of them suffered from neoplastic disease, one from TB of the intrathoracic nodes. The authors conclude that the importance of bronchoscopic examination in patients with pleural exudates is increasing due to the changed spectrum of basic diagnoses and that it should be made in all patients with an obscure pleural exudate. PMID- 2257588 TI - [Incidence of HBs-antigen in diabetics. III. Results of examination after 5 years]. AB - By examination of a group of 617 diabetics treated by oral antidiabetics (PAD) and 263 treated with insulin for HBs-antigen carriership (HBsAg) by counter immunoelectrophoresis (CIEP) a total of 34 HBsAg carriers were detected (3.84%). This number comprised 9 treated with PAD (1.5%) and 25 insulin-treated ones (9.5%). Only six were younger than 60 years, the remaining 28 were older. Comparison with results assembled in 1984 revealed that in both groups during the five-year interval a marked decline of the prevalence of carriership had occurred -in the PAD treated group from 4.9% to 1.5% and in the insulin treated group from 29.1% to 9.5%. The decline is above all due to the high mortality of diabetics who are HBsAg carriers. In the course of five years a total of 50% died. Formerly positive patients were, if CIEP was negative, examined also by the ELISA method. On examination by both methods 13 were negative (19.7%). Of the newly detected 14 carriers 7 suffered from cirrhosis of the liver, incl. five where examination of HBsAg revealed the disease. In eight patients the carriership was confirmed only by examination by the ELISA method. Of the latter five had previously alternately positive and negative results when examined by CIEP which indicates variations of the serum concentration of the antigen. PMID- 2257589 TI - [Idiopathic infantile hypercalcemia]. AB - Idiopathic infantile hypercalcaemia is a rare state characterized by failure to thrive, anorexia, vomiting, constipation and psychomotor retardation. We report a case of an infant with this syndrome. PMID- 2257590 TI - [60 years since the founding of the Medical Society in Olomouc]. PMID- 2257591 TI - [Rheumatology today and yesterday. Modern advances and future trends]. AB - The author mentions some recent advances from the sphere of clinical medicine and associated theoretical disciplines which may closely influence the future development of rheumatology. In addition to technical advances as regards visualization of tissue structures such as magnetic resonance and the development of artificial prostheses of damaged joints, molecular biology and genetics are the greatest advance as regards knowledge of the aetiopathogenesis of disease in particular those which have an immunopathological background. PMID- 2257592 TI - [The effect of nonsteroidal antirheumatic agents on articular cartilage]. AB - The authors submit a review on the influence of non-steroid anti-rheumatic drugs on the articular cartilage. First they review the general literature and then discuss the effect of different NSA on cartilage, taking into account their classification into six groups with regard to their chemical composition. Experience is based practically only on laboratory and experimental work and the results therefore cannot be mechanically applied in clinical medicine. However, NSA which do not have a negative impact on the cartilage of experimental animals are probably also safer in clinical practice. In this country the following NSA are available: diclofenac, piroxicam and thia profenic acid. PMID- 2257593 TI - [Serum amyloid A protein--a general acute phase reactant]. AB - Apoprotein SAA is analyzed from the aspect of its function of a general reactant of the acute stage--an indicator of the laboratory activity. The authors give general characteristics of this protein incl. the incidence and probable genesis of different isotypes. On several examples he demonstrates the lack of dependence between the incidence of isotypes and the development of amyloidosis or the basic pathological cause leading to laboratory activity. The simple relationship between the circulating precursor of SAA protein and the deposited AA amyloid fibrils is not unequivocal. Factors leading to the deposition of amyloid are, however, mentioned only liminally. The author discusses in more detail the induction of SAA protein formation at the level of genetic information which makes possible a potent acute response expressed by a rapid and brisk rise of plasma levels. PMID- 2257594 TI - [Levels of large proteoglycan aggregate binding proteins and the level of small proteoglycans in healthy human articular cartilage and in osteoarthrosis]. AB - The investigation was focused on the electronmicroscopic localization of one structure of the aggregate of the large proteoglycan--binding proteins and the small dermatan sulphate proteoglycan, using specific antibodies prepared against these structures and the complex colloid gold--protein A. The authors investigated the incidence and distribution of these structures in the intercellular area of ultrathin sections of the sound and arthritic human articular cartilage. In the arthritic cartilage, consistent with biochemical findings, the authors detected a loss of the binding protein or its disappearance and conversely an increase of the small dermatan sulphate proteoglycan. PMID- 2257595 TI - [Proteinases and their inhibitors in intervertebral discs]. AB - The authors investigated the incidence of proteinases and their inhibitors in bovine intervertebral discs. They proved the presence of proteinases of all basic enzyme classes. In some instances (in the class of cysteine proteinases) a more detailed specification of the present enzymes could be made. The authors proved also the presence of inhibitors of serine and cysteine proteinases which were characterized by relative molecular weights. The relative molecular weights were within the range of cca 7000 to cca 40,000. PMID- 2257596 TI - [Autoantibodies against histones and actin determined by western blotting in patients with rheumatic diseases]. AB - Using the Western blot method, the authors analyzed 85 sera obtained from patients with rheumatic diseases, focused on the presence of antihistones and antiactin autoantibodies. The authors detected a 32% incidence of the two investigated autoantibody specificities. In a group of 42 patients with systemic lupus erythematosus in 22 sera (52%) positive antihistone antibodies were present, whereby autoantibodies anti-H1 and anti-H2B were most frequent. In 15 sera in this group of patients (36%) antiactin autoantibodies were present. PMID- 2257597 TI - [Physician-martyrs of the Czech resistance during World War II. IV]. PMID- 2257598 TI - [New morphologico-functional concepts of sensory structures]. AB - The author analyzes the terminology of sensory nerve structures serving mechanoreception, nociception, thermoreception, chemoreception and baroreception which is not only very varied but also inaccurate, as it reflected so far only some morphological or functional phenomena. The author considers particularly inapt to use the term "receptor" for so-called nerve endings, as at present the term receptor stands for the specific binding capacity of protein molecules in particular in cell membranes, the transmission of information into the cell and evoking of a biological response. From the aspect of the contemporary concept the so-called nerve endings must be considered systems formed by a different number of sub-systems which participate in a certain way in the activity of the structure as a whole. This system is formed by the dendritic zone with the ability to form a generating potential, by modified Schwann cells, Grandry's on Merkel's modified fibrocytes, in corpuscles by fluid, a system of cellular lamellae and microfibrils and in Pacini's corpuscles also by a network of capillaries. Every sensory structure is associated metabolically with surrounding tissue. The author defines sensitive nervous formations as basic special sensory systems which serve the receipt of information and their transmission to the CNS and complex sensitive nervous formations which are systems of a higher order with an adaptive graded sensitivity. The author submits then his own classification of sensory nervous formations which respects morphological and functional phenomena which can be essentially summarized in two basic and one transient class. PMID- 2257599 TI - [Outlook on personnel requirements for ensuring professional diabetology care in the Czech Republic]. AB - The submitted prognosis of need of personnel to ensure specialist diabetological care in the Czech Republic is based on an analysis of the development of the number of diabetic patients and an analysis of activities which must be provided to diabetics in order to maintain the selected standard of health care. The estimate of the future number of diabetics is assessed by the method of demographic projection for one-year age groups, separately for men and women. The analysis of activities in diabetological care was elaborated from the results of an anonymous survey among diabetologists in the South Moravian region. Reflections on different variants of the standard of provided care respect also the analysis of the hitherto recorded trend in the number of health workers in diabetology and their available time. The estimate of needs is objective and can be applied in specialized diabetological services as well as in a different organization of care of diabetics, e.g. by the general practitioner. The contemporary organization of care of diabetics cannot ensure the required standard of care. The prognosis submits several possible ways how to achieve this standard. The prognosis deals in particular with the number of working hours of doctors but does not omit other categories of health workers. PMID- 2257600 TI - [Clinical course of recent insulin-dependent diabetes mellitus and possibilities of controlling it therapeutically]. AB - Intensive insulin treatment in a recent stage of IDDM promotes metabolic compensation of the disease regardless which regime of conventional or unconventional treatment is used. In thus treated patients more frequently complete or partial metabolic remission is achieved. C-peptide in patients in remission is much higher than in other patients, and conversely there are fewer persons without residual B-cell secretion. The manifestation of diabetes has an impact also on the clinical course of the disease. Normoglycaemia with possible metabolic remission associated with easy insulin administration a flexible lifestyle have a favourable effect on the onset of the life-long disease and eliminate to a minimum factors which have a negative psychosomatic impact on the patient. PMID- 2257601 TI - [Determination of bone mineral content in vivo in dialyzed patients using photon radiation absorptiometry]. AB - In a group of 47 women and 54 men with chronic renal failure included in a regular haemodialyzation programme the mineral content of bone was assessed using the method of radiation absorption of the radioisotope americium (241Am) on a Bone mineral detector of Gambro Co. The bone mineral content was reduced in men and women by 22%, as compared with healthy subjects of the same age and sex. The reduction was more marked in patients dialyzed for longer periods and when there were lamoratory signs of activity of the process. PMID- 2257602 TI - [The importance of benziodarone in the treatment of gout and hyperuricemic syndrome]. AB - The authors pay attention to benziodarone, a representative of the category of benzofurans. They test its effect on the uric acid serum level in normouraemic subjects as well as in hyperuricaemic syndrome and gouty arthritis. The hypouricaemic action of benziodarone (Amplivex-Labaz) is prompt. The maximum drop of uricaemia after Amplivex administration (2 tablets/day) occurs during the first three days. The uric acid level declines by as much as 80% of the baseline value. For long-term treatment 1 tablet per day is sufficient, in some instances even 1 tablet twice a week. The tolerance of the preparation is satisfactory. The authors deal also with the mechanism of action of benziodarone. Amplivex is not only a uricostatic but also a uricosuric agent. PMID- 2257603 TI - [Physician-martyrs in the Czech resistance during World War II. V]. PMID- 2257604 TI - Ontogenetic development of synovial A cells in fetal and neonatal rat knee joints. AB - Ontogenetic development of the synovial A cells in fetal rat knee joints was investigated by immunohistochemistry, immuno-electron microscopy, cultivation, and autoradiography. At day 17 of gestation, immature macrophages were first seen in the articular interzone, and thereafter they differentiated into macrophages (synovial A cells), which were found in the synovial intima. The degree of reactivity of macrophages with five monoclonal antibodies increased in the developing synovial membranes of fetal rats as shown by immunohistochemistry. Similar findings were obtained in organ cultures of fetal knee joints. A marked difference of proliferative potential was found between A and B cells during ontogeny. A cells after birth did not incorporate 3H-thymidine in contrast to B cells. Before birth, B cells had a labelling index which was at least five times larger than that of A cells. The results of this study indicate that the synovial A cells are derived from both monocytes and fetal macrophages circulating in peripheral blood and that they differ from the synovial B cells in morphology, differentiation, and proliferative potential. PMID- 2257605 TI - Lectin histochemistry of the human fetal subcommissural organ. AB - The subcommissural organ (SCO) of 7 human fetuses, 3 to 6.5 months old, was investigated by means of: (i) immunocytochemistry employing three different antisera against secretory products extracted from the bovine SCO and Reissner's fiber; (ii) lectin binding using concanavalin A (Con A; affinity: mannose, glucose), wheat-germ agglutinin (WGA; affinity: N-acetyl-glucosamine, sialic acid), and Limax flavus agglutinin (LFA; affinity: sialic acid). Sections of bovine SCO were processed simultaneously and examined for comparative purposes. The human fetal SCO displayed lectin-binding properties identical to those in the SCO of other mammals. Thus, Con A-binding sites were restricted to abundant supranuclear structures that most likely corresponded to the rough endoplasmic reticulum, but were missing from granules located in the apical cytoplasm. The latter secretory material was strongly WGA- and LFA-positive and formed a distinct zone in the most apical portion of the ependymal cells. In contrast, this type of reactivity was missing in the adjacent cells of ependyma proper. In the bovine SCO, LFA-positive granules were also aggregated in an apical layer. The secretory material in the bovine SCO, especially its apical granular component, was strongly immunoreactive with the three antisera used; the human fetal SCO, however, lacked this immunoreactivity. It is postulated that the SCO of human fetuses secretes glycoproteins with a carbohydrate chain similar to--and a protein backbone different from--the secretions elaborated by the SCO of other vertebrate species. PMID- 2257606 TI - Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor. III. Changes in DNA synthesis and mitotic activity. AB - Previous studies with rats have shown that a single oral dose of the proteinase inhibitor Camostate (FOY-305) induces release of cholecystokinin (CCK) into the circulation, which lasts for 3 to 6 h. This transient endogenous release of hormone results in a depletion of pancreatic enzyme stores within 1 h and an increase in total rate of protein synthesis, which peaks at 6 to 9 h. At the level of individual enzyme biosynthesis a transient decrease in amylase and an increase in trypsinogen and chymotrypsinogen is observed. In the present study the time course of DNA synthesis and the labeling index of 5 populations of pancreatic cells have been analysed following a single oral dose of 50 or 100 mg/kg proteinase inhibitor, using in vivo labeling with 12 microCi/g body weight 3H-thymidine 1 h prior to sacrifice of the animals. DNA synthesis did not change during the initial 12 h following inhibitor feeding and then showed a phasic increase with a peak (20-fold) at 24 h and intermediate increases (4- to 5-fold) at 18 and 36 h, respectively. From the 5 pancreatic cell populations studied by autoradiography the labeling indices of interlobular duct cells and islet cells did not change over the entire observation period. Acinar cells, intralobular duct cells and interstitial cells showed a marked increase in labeling index with peak values at 24 h, which were 20-fold in acinar cells and 5.5- and 8.5-fold in intralobular duct cells and interstitial cells, respectively. The data demonstrate a significant growth response of pancreatic acinar tissue after a single episode of endogenous CCK-release, which is similar in extent, time course and cellular source as previously demonstrated during persistent stimulation of the pancreas by prolonged infusion of the CCK-analogue caerulein. PMID- 2257607 TI - Immunocytochemical localization of oxytocin in corpora lutea and luteinized cysts from anoestrous ewes stimulated with gonadotrophin-releasing hormone. AB - Anoestrous Romney Marsh ewes with or without progesterone pretreatment were injected with multiple low-doses of gonadotrophin-releasing hormone followed by a single, larger bolus. Blood samples were taken at twelve-hourly intervals for progesterone radioimmunoassay. Ewes were slaughtered on day 3 or 5 after the bolus injection, and the ovaries were collected for histology and immunocytochemical examination for oxytocin-immunoreactivity. The corpora lutea of all ewes killed on day 3 had similar weights and morphology. The ovaries of those ewes which were not pretreated with progesterone also contained some luteinized cysts. Ewes slaughtered on day 5 were separated into 2 groups according to plasma progesterone profiles, which were either rising ('normal'), or falling after a transitory rise ('abnormal'). Those ewes pretreated with progesterone all had a 'normal' progesterone profile whereas, of 14 ewes not pretreated with progesterone, 6 were 'normal' and 8 'abnormal'. Corpora lutea were significantly lighter in the 'abnormal' group and the ovaries of most of these ewes also contained luteinized cysts. All corpora lutea and luteinized cysts showed staining for oxytocin-immunoreactivity although the staining intensity was variable. In corpora lutea from 'normal' ewes oxytocin was restricted to large luteal cells. In addition tissues from 'abnormal' ewes also contained many cells with an atypical elongated shape which stained for oxytocin immunoreactivity. These results show that progesterone pretreatment is needed for both normal morphological and endocrine development of corpora lutea in anoestrous ewes stimulated with gonadotrophin-releasing hormone. PMID- 2257608 TI - Circadian changes in synaptic ribbons and spherules in pinealocytes of the Syrian hamster (Mesocricetus auratus). AB - In the present study, "synaptic" ribbons were studied morphologically and quantitatively in hamster pineal gland. The number of ribbons and spherules of hamster pinealocytes was counted over a 24-h period. The 24-h variations in the quantity of "synaptic" ribbons were found to parallel fluctuations in pineal melatonin concentrations. No significant circadian changes were observed for "synaptic" spherules, indicating different roles for these two structures. PMID- 2257609 TI - Stereological study of gonadotropes in the frog, Rana pipiens, after GnRH stimulation in vitro. AB - Previous physiological results have indicated the existence of two releasable pools of gonadotropins in amphibian pituitaries: an acute releasable pool that appears independent of protein synthesis, and a storage pool involved in chronic release that depends on protein synthesis. To elucidate the ultrastructural localization of these pools and the morphological changes induced in gonadotrope cells after treatment with gonadotropin-releasing hormone, we carried out a morphometric study of immuno-identified gonadotrope cells using an in vitro superfusion system. Treatment with gonadotropin-releasing hormone induced a degranulation of small (110-255 nm) and medium (236-360 nm) secretory granules as well as hypertrophy of the endoplasmic reticulum and Golgi complex. Simultaneous incubation with gonadotropin-releasing hormone and cycloheximide inhibited the release of secretory granules although the endoplasmic reticulum and Golgi complex were hypertrophied. These morphological results strongly suggest: (1) that gonadotropin-releasing hormone induces degranulation and hypertrophy of the biosynthetic machinery in gonadotrope cells; and (2) that the activation of the endoplasmic reticulum and Golgi complex by stimulation with gonadotropin releasing hormone is independent of protein synthesis, while the release of secretory granules is protein synthesis-dependent. In addition, the second or "storage" pool of gonadotropin is associated mainly with the small and medium secretory granules. PMID- 2257610 TI - The passage of macrophage and lymphocytes from the interstitium across the lymphatic endothelium of rat lacteals. AB - The passage of cells across the lymphatic endothelium of rat lacteals in both normal and non-pathological experimental conditions (fasting, lymphatic, stasis) was studied by means of serial thin sections and three-dimensional models. Two different pathways of transendothelial migration were observed: (1) macrophages enter the lymphatic lumen via the cytoplasm of endothelial cells, without involvement of intercellular junctions, whereas (2) lymphocytes migrate through "intraendothelial channels", dynamic structures organized by the lymphatic endothelium under physiological conditions. PMID- 2257612 TI - Microfibrils: a constitutive component of reticular fibers in the mouse lymph node. AB - Fibrous components other than collagen fibrils in the reticular fiber of mouse lymph node were studied by electron microscopy. Bundles of microfibrils not associated by elastin and single microfibrils dispersed among collagen fibrils were present. The diameter of the microfibrils was 13.29 +/- 2.43 nm (n = 100). Elastin-associated microfibrils occurred at the periphery of the reticular fiber. Elastin was enclosed by microfibrils, thus forming the elastic fiber, which was clearly demonstrated by tannic acid-uranyl acetate staining. In the reticular fiber of lymph nodes, the elastic fiber consisted of many more microfibrils and a small amount of elastin. These microfibrils, together with the collagen fibrils, may contribute to the various functions of the reticular fibers. PMID- 2257611 TI - Existence of an endothelio-endothelial placenta in the insectivore, Suncus murinus. AB - The interhemal membrane of the chorioallantoic placenta in the insectivore Suncus murinus was investigated by means of electron microscopy. In the interhemal membrane the syncytiotrophoblast clearly intervened between the hypertrophied maternal endothelium and the fetal endothelium by day 20 of pregnancy. Although the syncytiotrophoblast showed a sieve-like feature from day 20 to 24, it was distinctly continuous. The syncytiotrophoblast, however, became discontinous in most areas of the labyrinthine zone after day 24, and finally both projections of the maternal and the fetal endothelium contacted each other. These findings indicate the focal existence of an endothelio-endothelial condition within an otherwise endothelio-chorial placenta. PMID- 2257613 TI - Glycosyl receptors in macrophage subpopulations of rat spleen and lymph node. A comparative study using neoglycoproteins and monoclonal antibodies ED1, ED2 and ED3. AB - We have developed an immunohistochemical method for the in vivo and in vitro detection of glycosyl receptors in rat spleen and lymph nodes by using neoglycoproteins. The receptor in both organs recognized mannose coupled to bovine serum albumin (mannose-BSA), fucose-BSA, N-acetylglucosamine-BSA and to a lesser extent glucose-BSA, but not galactose-BSA or N-acetyl-galactosamine-BSA. In vitro neoglycoprotein-receptor binding was Ca2+ dependent and could be inhibited by mannan but not by mannose. Simultaneous staining with the monoclonal antibodies ED1, ED2 or ED3 revealed that only ED1- and ED3-positive macrophages were involved in the binding of neoglycoproteins. In the spleen, the marginal zone macrophages and a subpopulation of the marginal metallophils possess glycosyl-binding receptors. In the lymph nodes, the medullary sinus macrophages and a subpopulation of the outer-cortex macrophages are able to bind neoglycoproteins. PMID- 2257615 TI - Intragranular co-storage of neuropeptide Y and arginine vasopressin in the paraventricular magnocellular neurons of the rat hypothalamus. AB - Certain populations of arginine vasopressin (AVP) neurons in the magnocellular paraventricular nucleus became immunoreactive for neuropeptide Y (NPY) when rats were treated with colchicine or monosodium glutamate (MSG). The co-storage of these peptides was examined by employing a post-embedding electron-microscopic immunohistochemistry technique using gold-labeled antibodies to the two peptides. In colchicine-treated rats, the neuronal perikarya contained numerous secretory granules showing co-storage of the two peptides. The cells of the MSG-treated rats were characterized by having well-developed Golgi bodies with the granular structures also co-storing the two peptides, although the secretory granules in the perikarya were rather fewer than in the colchicine-treated rats. It is concluded that the destruction of the arcuate nucleus by MSG-treatment may potentiate the synthesis of NPY in AVP neurons, the synthesis of which is latent in intact animals. PMID- 2257614 TI - Effects of prolactin on the morphology and function of rat Leydig cells: short term versus long-term administration. AB - The bolus administration of prolactin (PRL) to adult rats did not cause any apparent change in the basal and luteinizing hormone (LH)-stimulated blood levels of testosterone (as estimated by radioimmune assay). Prolonged PRL infusion did not affect either basal testosterone plasma concentration or the morphology of Leydig cells (as evaluated by electron microscopy and stereology). Conversely, prolonged PRL treatment notably increased the gonadotrophic effects of chronic LH administration; this mainly consisted of a rise in the blood concentration of testosterone and a conspicuous hypertrophy of Leydig cells. The LH-induced increase in the volume of Leydig cells was the result of an increase in the volumes of all the organelles involved in steroid synthesis (i.e., smooth endoplasmic reticulum, peroxisomes and mitochondria). However, the trophic effects of PRL infusion exclusively concerned smooth endoplasmic reticulum and peroxisomes. In the light of these findings, the hypothesis is advanced that the mechanism underlying the gonadotrophic action of PRL involves an enhancement of the endogenous cholesterol synthesis, which could provide an abundance of precursors for testosterone synthesis, the post-cholesterol steps of which, in turn, would be exclusively controlled by LH. PMID- 2257616 TI - Cryo-electron microscopy of vitrified nerve myelin. AB - The ultrastructure of rat optic and trigeminal nerve myelin was studied using different cryotechniques. Replicas of rapid cryofixed and deep-etched material were compared with cryosections of chemically unfixed specimens and also of glutaraldehyde-fixed specimens. Hydrated cryosections were analysed in a cryotransfer device. The data reported here show discrepancies with the current descriptions of myelin structure based on osmium-fixed and resin-embedded material. The structures called the major line (as a fusion of the cytoplasmic surfaces of the glial cells) in conventional electron microscopy and the intraperiod line (as a fusion of the outer surfaces) are seen in the present material to represent actually aqueous spaces. The extracellular space (E-space) is most sensitive to chemical fixation and other preparation procedures, and probably also expands under pathological conditions. The virtual C-space (cytoplasmic space = major line) is more stable. The cytoplasmic surfaces are most probably joined by globular proteins (myelin basic protein). The most compact organization of myelin is seen in fresh, unfixed nerves. A continuous bilayer could not be observed and the bilayer membrane showed particulate subunits. PMID- 2257617 TI - Urinary bladder of rat: fine structure of normal and hypertrophic musculature. AB - The fine structure of the muscle of the urinary bladder in female rats is similar to that of other visceral muscles, although it is arranged in bundles of variable length, cross-section and orientation, forming a meshwork. When distended, the musculature is 100-120 microns thick, with some variation and occasional discontinuity. Extended areas of cell-to-cell apposition with uniform intercellular space occur between muscle cells, whereas attachment plaques for mechanical coupling are less common than in other visceral muscles. There are no gap junctions between muscle cells. Many bundles of microfilaments and small elastic fibres run between the muscle cells. After chronic partial obstruction of the urethra, the bladder enlarges and is about 15 times heavier, but has the same shape as in controls; the growth is mainly accounted for by muscle hypertrophy. The outer surface of the hypertrophic bladder is increased 6-fold over the controls; the muscle is increased 3-fold in thickness, and is more compact. Mitoses are not found, but there is a massive increase in muscle cell size. There is a modest decrease in percentage volume of mitochondria, an increase in sarcoplasmic reticulum, and no appreciable change in the pattern of myofilaments. Gap junctions between hypertrophic muscle cells are virtually absent. Intramuscular nerve fibres and vesicle-containing varicosities appear as common in the hypertrophic muscle as in controls. There is no infiltration of the muscle by connective tissue and no significant occurrence of muscle cell death. PMID- 2257618 TI - Migration of myogenic cells in the rat extensor digitorum longus muscle studied with a split autograft model. AB - The ability of myogenic cells to migrate perpendicular to the long axis of freely autografted muscles was examined. Rat extensor digitorum longus muscles were divided, and one half was devitalized by repeated freezing in liquid nitrogen while the other half was kept viable in physiologic saline. The halves were reunited with sutures and grafted back into the original muscle bed. At intervals between 5 and 25 days the grafts were removed and examined histologically for the presence of myotubes within the devitalized region. Myotubes were first seen in the devitalized half 10 days postgrafting with the maximum number of myotubes observed after 12 to 15 days. These results indicate that myogenic cells are capable of migration perpendicular to the long axis of the muscle fibers in an autograft. PMID- 2257619 TI - A morphometric comparison of the olfactory epithelium of newborn and weanling rabbits. AB - As part of a study of the development of olfactory function in the rabbit, a morphometric analysis of the olfactory epithelium in newborn and 30-day-old animals was carried out. Surface area, thickness and cell densities of the olfactory epithelium were compared in hematoxylin-eosin stained serial sections through the nasal cavities of 4 newborn and 3 weanling rabbits. While the basic structure of the olfactory cavity changed little with age, a large quantitative development in the epithelium was observed. The pattern of growth appeared uniform and resulted in a 3-fold increase in total surface area from about 1 cm2 per side in the newborn to about 3 cm2 in the weanling, and an increase in thickness from approximately 65 microns to about 90 microns. The increase in thickness was due mainly to a disproportionate, 5-fold increase in the number of olfactory neurons. This resulted in a total of about 32 million cells per side by day 30, and represented an increase in the ratio of neurons to basal cells of 7:1 to 10:1, and neurons to supporting cells of 2:1 to 4:1. While such an increase in the number of primary neurons presumably improves the animal's perceptual abilities, it nevertheless raises the question as to how perceptual constancy can be maintained during a period of such rapid neural change. PMID- 2257620 TI - Changes in renal morphology and renin secretion in the golden-mantled ground squirrel (Spermophilus lateralis) during activity and hibernation. AB - Chronological changes in renal glomerular morphology and plasma renin activity were investigated during active and hibernating periods in the golden-mantled ground squirrel Spermophilus lateralis. The objective of this study was to determine whether the glomerular endothelium, visceral epithelium (podocytes), basement membrane, mesangial cells, proximal convoluted tubule cells and plasma renin activity exhibit measurable sequential differences between as well as within active and hibernating states at various time points. Limitations in the size of the experimental population prevented an evaluation of changes in these parameters during other important periods such as periodic arousal between hibernation bouts. In this study, glomerular endothelial pore number and epithelial filtration slit number significantly decreased by early hibernation when compared to those during summer activity, and then they increased back toward summer levels by late hibernation. In contrast, podocytic pedicel width along the glomerular basement membrane increased from summer activity to early hibernation, before significantly decreasing again by late hibernation. Mesangial cell and proximal convoluted tubule cell activity appeared increased during hibernation as compared to summer activity, whereas the width of the glomerular basement membrane showed no significant alterations throughout. Plasma renin activity significantly increased during early hibernation and mid-hibernation when compared to summer levels but had decreased by late hibernation toward summer values. The glomerular and plasma renin activity changes observed in this study clearly illustrate the drastic structural and functional adjustments which hibernating species make during torpor and also correlate well with the reported decrease in renal perfusion pressure and urine formation during hibernation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257621 TI - Single amino acid substitutions in one Ca2+ binding site of uvomorulin abolish the adhesive function. AB - We show that a synthetic peptide corresponding to the sequence of one putative Ca2+ binding motif of the cell adhesion molecule uvomorulin is able to complex Ca2+. This function is abolished if the first Asp in the peptide is replaced by Lys. Accordingly, we expressed in L cells mutant uvomorulin with a replacement of Asp to Lys or Ala. Mutant protein was resistant to Ca2+/trypsin under mild conditions but became susceptible at or near the site of replacement at higher concentrations, leaving the remaining Ca2+ binding domains protected. Remarkably, in cell aggregation assays both mutant uvomorulins failed to mediate cell adhesiveness, demonstrating that a single amino acid substitution in one Ca2+ binding site inactivates the adhesive function. PMID- 2257622 TI - Courtship in S. cerevisiae: both cell types choose mating partners by responding to the strongest pheromone signal. AB - We demonstrate that during the courtship stage of conjugation, S. cerevisiae a cells choose the alpha cell producing the highest level of pheromone from among potential mating partners. From this result and that for alpha cells we conclude that both a and alpha cells act as signaling cells during courtship, that both cell types respond by discriminating different levels of signal, and that the signals are the mating pheromones. Responding cells that are supersensitive to signal fail to discriminate pheromone-producing from nonproducing cells to an extent that depends on their degree of supersensitivity. We propose that partner selection in S. cerevisiae results from polarized morphogenesis of a responding cell in the direction of highest pheromone concentration and that cells defective in discriminating this gradient execute a default pathway in which an adjacent cell is selected at random. PMID- 2257623 TI - The E. coli cell surface specifically prevents the initiation of DNA replication at oriC on hemimethylated DNA templates. AB - A particular outer membrane fraction previously defined as possessing specific affinity for the hemimethylated form of the origin of replication of the E. coli chromosome (oriC) is shown to inhibit the initiation of DNA synthesis at this site on hemimethylated DNA templates in vitro. The replication of fully methylated or unmethylated DNA templates is not affected. Also, no inhibition is observed if initiation takes place at random sites on the hemimethylated template. The key inactivation step appears to be membrane inhibition of DnaA initiator protein binding to oriC. Remethylation of the membrane-bound hemimethylated DNA results in reactivation. Our results demonstrate direct involvement of the membrane in the control of DNA replication. We propose that association/dissociation of the origin from the cell membrane is one of the control elements governing interinitiation times in E. coli. PMID- 2257624 TI - Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis. AB - Using detailed functional studies on 24 human transferrin receptor mutants, we identified YXRF as the internalization sequence. Provided that at least 7 residues separate this tetrapeptide from the transmembrane region, changing the tetrapeptide position within the TR cytoplasmic domain does not reduce internalization activity. Thus, any conformational determinant for internalization must be localized to the YXRF sequence. Twenty-eight tetrapeptide analogs of YXRF, found by an unbiased search of all known three-dimensional protein structures, significantly favored tight turns similar to a type I turn. Of the ten tetrapeptides most closely related to YXRF, eight were surface exposed and had tight-turn conformations, as were four of five tetrapeptides with sequences related to the low density lipoprotein receptor internalization motif, NPXY. The internalization sequences of both receptors contain aromatic residues with intervening hydrogen-bonding residues. Thus, two distinct internalization sequences favor a common structural chemistry and implicate an exposed tight turn as the recognition motif for high efficiency endocytosis. PMID- 2257625 TI - Molecular cloning and expression of a hexameric Drosophila heat shock factor subject to negative regulation. AB - We report the cloning of the transcriptional activator of heat shock genes, HSF, from Drosophila. The predicted sequence of Drosophila HSF protein is surprisingly divergent from that of yeast HSF, except in regions important for DNA binding and oligomerization. A segment of the DNA binding domain of HSF bears an intriguing similarity to the putative DNA recognition helix of bacterial sigma factors, while the oligomerization domain contains an unusual arrangement of conserved hydrophobic heptad repeats. Drosophila HSF produced in E. coli under nonshock conditions forms a hexamer that binds specifically to DNA with high affinity and activates transcription from a heat shock promoter in vitro. In contrast, when HSF is expressed in Xenopus oocytes, maximal DNA binding affinity is observed only after heat shock induction. These results suggest that Drosophila HSF has an intrinsic affinity for DNA, which is repressed under nonshock conditions in vivo. PMID- 2257626 TI - Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. AB - Humans who have inherited the human class I major histocompatibility allele HLA B27 have a markedly increased risk of developing the multi-organ system diseases termed spondyloarthropathies. To investigate the role of B27 in these disorders, we introduced the B27 and human beta 2-microglobulin genes into rats, a species known to be quite susceptible to experimentally induced inflammatory disease. Rats from one transgenic line spontaneously developed inflammatory disease involving the gastrointestinal tract, peripheral and vertebral joints, male genital tract, skin, nails, and heart. This pattern of organ system involvement showed a striking resemblance to the B27-associated human disorders. These results establish that B27 plays a central role in the pathogenesis of the multi organ system processes of the spondyloarthropathies. Elucidation of the role of B27 should be facilitated by this transgenic model. PMID- 2257627 TI - Origins of human cancer revisited. PMID- 2257628 TI - The unc-86 gene product couples cell lineage and cell identity in C. elegans. AB - The C. elegans gene unc-86 is required in several distinct neuroblast lineages for daughter cells to become different from their mothers, and is also required for the specification of particular neural identities. Consistent with the fact that unc-86 encodes a POU domain protein, we find that the unc-86 protein is localized to the nucleus. In the affected lineages, unc-86 protein appears within a few minutes after cell division in the nuclei of those daughter cells that are transformed by unc-86 mutations. Thus, expression of unc-86 protein is dependent on cell lineage. unc-86 protein is not asymmetrically segregated at further divisions. unc-86 protein also appears shortly after cell division in the nuclei of particular identified differentiating neurons; at least some of these neurons are nonfunctional in unc-86 mutants. PMID- 2257630 TI - The expression and posttranslational modification of a neuron-specific beta tubulin isotype during chick embryogenesis. AB - Five beta-tubulin isotypes are expressed differentially during chicken brain development. One of these isotypes is encoded by the gene c beta 4 and has been assigned to an isotypic family designated as Class III (beta III). In the nervous system of higher vertebrates, beta III is synthesized exclusively by neurons. A beta III-specific monoclonal antibody was used to determine when during chick embryogenesis c beta 4 is expressed, the cellular localization of beta III, and the number of charge variants (isoforms) into which beta III can be resolved by isoelectric focusing. On Western blots, beta III is first detectable at stages 12 13. Thereafter, the relative abundance of beta III in brain increases steadily, apparently in conjunction with the rate of neural differentiation. The isotype was not detectable in non-neural tissue extracts from older embryos (days 10-14) and hatchlings. Western blots of protein separated by two-dimensional gel electrophoresis (2D-PAGE) reveal that the number of beta III isoforms increases from one to three during neural development. This evidence indicates that beta III is a substrate for developmentally regulated, multiple-site posttranslational modification. Immunocytochemical studies reveal that while c beta 4 expression is restricted predominantly to the nervous system, it is transiently expressed in some embryonic structures. More importantly, in the nervous system, immunoreactive cells were located primarily in the non-proliferative marginal zone of the neural epithelia. Regions containing primarily mitotic neuroblasts were virtually unstained. This localization pattern indicates that c beta 4 expression occurs either during or immediately following terminal mitosis, and suggests that beta III may have a unique role during early neuronal differentiation and neurite outgrowth. PMID- 2257629 TI - let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein. AB - Genetic analysis previously suggested that the let-60 gene controls the switch between vulval and hypodermal cell fates during C. elegans vulval induction. We have cloned the let-60 gene, and shown that it encodes a gene product identical in 84% of its first 164 amino acids to ras gene products from other vertebrate and invertebrate species. This conservation suggests that the let-60 product contains all the biochemical functions of ras proteins. Extrachromosomal arrays of let-60 ras DNA cause cell-type misspecification (extra vulval fates) phenotypically opposite to that caused by let-60 ras loss-of-function mutations (no vulval fates), and suppress the vulvaless phenotype of mutations in two other genes necessary for vulval induction. Thus, the level and pattern of let-60 ras expression may be under strict regulation; increase in let-60 ras activity bypasses or reduces the need for upstream genes in the vulval induction pathway. PMID- 2257632 TI - Structure and function of profilin. PMID- 2257631 TI - Reorganization of circumferential microfilament bundles in retinal epithelial cells during mitosis. AB - To examine the behaviour of the apical circumferential microfilament bundles (CMBs) associated with the zonula adhaerens (ZA)-junctions during mitosis, retinal pigment epithelial cells were labelled for F-actin, and retinas were serially sectioned for TEM. The results show that the ZA-CMB-complex persists throughout all stages of mitosis. At metaphase, the cells round up, but stay joined apically to adjacent cells by ZA-junctions. At telophase, the cleavage furrow forms asymmetrically from the basal end progressively toward the apical end, where the daughter cells remain connected by an intercellular bridge (IB). As the cleavage furrow with the contractile ring (CR) approaches the CMB, the two microfilament (MF) systems are oriented perpendicularly to each other. At the level of the CMB, the MFs of the CR connect the opposite sides of the CMB and bisect it into two CMBs, one for each of the two daughter cells. Subsequently, the CR in the IB splits into two, one on either side of the midbody. The two daughter cells, having acquired a complete CMB of their own, do not become direct neighbours, since adjacent cells, which remain joined to the apical ZA-junction of the dividing cell, are observed in the cleavage furrow, where they meet and form a ZA-junction between themselves, just below the IB. Separation of the daughter cells without losing contact with neighbouring cells at the level of the apical ZA-junction thus maintains the integrity of the epithelial sheet during mitosis. PMID- 2257633 TI - Identification of an amino acid substitution in the benA, beta-tubulin gene of Aspergillus nidulans that confers thiabendazole resistance and benomyl supersensitivity. AB - We are using molecular genetic techniques to identify sites of interaction of beta-tubulin with benzimidizole anti-microtubule agents. We have developed a marker-rescue technique for cloning mutant alleles of the benA, beta-tubulin gene of Aspergillus nidulans and have used the technique to clone two mutant benA alleles, benA16 and benA19. These are the only A. nidulans alleles known to confer resistance to the benzimidazole antimicrotubule agent thiabendazole and supersensitivity to other benzimidazole antimicrotubule agents including benomyl and its active breakdown product, carbendazim. benA16 has been shown, moreover, to reduce thiabendazole binding to beta-tubulin. We have sequenced the two mutant alleles and have found that they carry different nucleotide changes that cause the same single amino acid substitution, valine for alanine at amino acid 165. Since thiabendazole and carbendazim differ at only one side chain, the R2 group, we conclude that the region around amino acid 165 is involved in the binding of the R2 group of benzimidazole antimicrotubule agents to beta-tubulin. PMID- 2257634 TI - Neurite elongation is blocked if microtubule polymerization is inhibited in PC12 cells. AB - We have injected process-bearing PC12 cells with colchicine-tubulin mixed with either fluorescein-dextran or a rhodamine-labelled tubulin analogue to determine the role of microtubule polymerization in neurite elongation. Colchicine-tubulin is a specific, substoichiometric poison of microtubule assembly. We have shown that colchicine-tubulin does not cause existing PC12 microtubules to disassemble, and yet can inhibit the assembly of rhodamine-tubulin injected along with it. In population studies of neurite outgrowth in injected and uninjected cells, we find that colchicine-tubulin substantially inhibits neurite extension from injected cells over a wide variety of concentrations. In acute time-course studies of injected cells, we find that colchicine-tubulin does not block neurite outgrowth until the injectate reaches the neurite tip. Thereafter, however, it blocks process elongation completely. Thus we can conclude that microtubule polymerization in the region of the growth cone is an important element in neurite elongation. While polymerization at the cell body may be important in supplying subunits to the distal neurite, it does not play a direct role in process extension. PMID- 2257635 TI - Absorption enhancers. AB - Many current therapeutic drugs, e.g., antibiotics and peptide drugs, are impermeable to outer tissue barriers. Drug delivery of impermeable drugs through such barriers is currently one of the major interests in pharmaceutical research. New classes of absorption enhancers provide rapid absorption in the gastrointestinal tract or skin, with no side effects. This review covers the history of enhancer research, an overview of a variety of absorption enhancers, the nature of enhancing action, and site specificity. The final section focuses on the mechanisms of enhancer action which transiently abolishes or reverses barrier resistance, from the viewpoints of the lipid bilayer barrier containing SH proteins, as well as transcellular/paracellular pathways. Fully understanding these mechanisms is of importance for therapeutic applications. PMID- 2257636 TI - Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine. AB - Since the appearance of the first therapeutic active peptides and proteins produced by genetic engineering, there has been an ever-increasing demand to be able to deliver these drugs by routes other than the parenteral. For most drugs the need for alternative delivery systems is due to short-half lives in the bloodstream, large extents of first pass metabolism, or the possibility of obtaining endogenous-like plasma profiles. A wide variety of drugs have now been tested for bioavailability after respiratory, especially intranasal, administration. A small range of drugs (such as propranolol and progesterone) appears to be absorbed effectively via the nasal route and shows bioavailabilities comparable to the intravenous route. However, most drugs shows a much lower degree of absorption. The present review discusses the critical steps that have to be considered when attempting to deliver drugs effectively via the nasal and pulmonary routes and how it is possible by suitable formulation of delivery systems to overcome some of the most important barriers to drug absorption. Furthermore, the immunological responses to respiratory absorption of exogenous peptides and proteins and the potential for development of locally administered vaccines are reviewed. PMID- 2257637 TI - Ultraviolet action spectrum for intracellular free Ca2+ increase in human epidermal keratinocytes. AB - Effects of UV on normal human epidermal keratinocytes were studied by measuring the intracellular free Ca2+ concentration ([Ca2+]i) using fluorescence ratio imaging (fura-2-AM). Upon UV irradiation the [Ca2+]i increased sharply after a certain lag time, and the UV sensitivity was higher at lower temperatures. Statistically the distribution of [Ca2+]i became broader as the mean values became larger, and the number of affected cells increased sharply above a certain fluence (light intensity x time [photons/cm2]) at all wavelengths studied (200 400 nm). The action spectrum showed a single peak at about 230 nm and decreased gradually toward longer-wavelength UV regions. PMID- 2257638 TI - Ultrastructural localization of fibronectin and laminin in human granulation tissue in relation to capillary development. AB - The distribution of fibronectin (FN) and laminin (LM) at developing capillaries during various developmental stages, from capillary sprouts to relatively developed capillaries, was studied by light- and electron-microscopy immunocytochemistry. By light-microscope, FN immunoreactivity was diffusely distributed throughout the stroma of the granulation tissues, while for LM it was preferentially distributed at the perivascular region with the various developmental stages of the immature capillaries. Ultrastructural study revealed that capillary sprouts were closely surrounded by plentiful deposits of immunoreaction with the FN, but only faintly for LM. Relatively developed capillaries with large and tall endothelium were surrounded by plentiful immunoreactive products with both FN and LM, and immunoreactivities in the cisternae of rER of the endothelium and/or the pericytes were also shown. Cytoplasmic interdigitations between the endothelium and the pericyte of developing capillaries were recognized without an immunoreaction for FN and LM. These results mean that the capillary sprouts are associated with a prepatterned FN-rich and LM-poor perivascular matrix, whereas relatively developed capillaries are associated with a FN- and LM-rich perivascular matrix which would have been produced by the capillary endothelium and/or pericytes. PMID- 2257639 TI - Transformation by v-H-ras does not restore proliferation of a set of temperature sensitive cell-cycle mutants of rat 3Y1 fibroblasts. AB - Three temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts (3Y1tsD123, 3Y1tsG125, and 3Y1tsH203, each belonging to distinct complementation groups) were transformed with plasmid DNA carrying Harvey murine sarcoma virus cDNA. The criteria for transformation were increase in saturation cell density, capability to clone in soft agar, and alteration in the cellular morphology. At 39.8 degrees C (restrictive temperature of the parental cell lines), all the transformed sublines of each mutant ceased to proliferate and were arrested reversibly in the G1 phase of the cell cycle like the parental lines. At both 39.8 degrees C and 33.8 degrees C (permissive temperature for the parental lines), all the untransformed parental lines synthesized p21ras at low rate. At 33.8 degrees C, all the transformed sublines synthesized p21ras at much higher rate and expressed the morphological phenotype characteristic to v-H-ras-induced transformation. At 39.8 degrees C, the rate of p21ras synthesis was not changed in the transformed sublines of 3Y1tsD123 and 3Y1tsG125, and the morphology of transformed phenotype also remained intact. In the transformed subline of 3Y1tsH203, the rate of p21ras synthesis was lowered at 39.8 degrees C to that seen in the untransformed parental line, and the transformed phenotype in morphology disappeared. In all of the transformed sublines, the amount of v-H-ras mRNA markedly expressed at both 33.8 degrees C and 39.8 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257640 TI - Solubilization of aster-forming proteins from yeast: possible constituents of spindle pole body and reconstitution of asters in vitro. AB - Spindle pole bodies (SPBs) attached to nuclei were isolated from Saccharomyces cerevisiae; they nucleated microtubules to form asters in vitro. This aster forming activity was stable in 30% dimethylsulfoxide or 10% 2-propanol and could be solubilized with KCl. The KCl extract contained many protein components, which aggregated upon dialysis against a low concentration salt solution. When incubated with tubulin, the aggregates formed asters. Measurements of the elongation rates of the astral microtubules indicated that the microtubules were nucleated from the SPBs or from the aggregates reconstructed from the KCl extract by dialysis. The plus end was distal to the astral center, as in the case of the microtubule organizing center (MTOC) of mammalian cells. We suggest that the proteins extracted with KCl are responsible for microtubule nucleation in SPBs and that this SPB seems to have the same mechanism for microtubule nucleation as the MTOC in higher eukaryotes. PMID- 2257641 TI - Cytoskeleton in human mammary carcinoma cells forming three-dimensional cellular structures within collagen gels. AB - Human mammary carcinoma cell line MCF-7 cells grown on type I collagen gels floating in a medium occasionally invaginated into the gels as a cell mass and formed cylindrical or domed structures within it. The 0.05% Triton-insoluble cytoskeleton of such cellular structures sedimented as a white flocculent layer at the boundary between 60 and 70% sucrose layers by ultracentrifugation, and consisted of 4 basal components: 54-kD (beta-tubulin), 45-kD, 42-kD (actin), and 39-kD polypeptides. By contrast, the isolated cytoskeleton of MCF-7 cells grown as monolayers on plastic substratum formed a finer cytoskeletal network with a smaller buoyant density and consisted of two distinct polypeptides with apparent molecular sizes of 80-kD and 65-kD in addition to the 4 basal components found in the morphologically developing cells. The present results indicate that the cytoskeleton of MCF-7 cells forming the three-dimensional cellular structures within collagen gels is lacking in these two polypeptides, and that it has a coarser cytoskeletal network with a greater buoyant density than that of the monolayered cells on plastic. PMID- 2257642 TI - [Limited photocoagulation in a case of macular edema caused by decrease of venous circulation]. PMID- 2257643 TI - [Limitations of photocoagulation in the treatment of diabetic maculo-foveolar edema: involvement of the peri-foveolar anastomotic mesh]. PMID- 2257644 TI - [Centro-foveolar exsudates in diabetic retinopathy]. PMID- 2257645 TI - [Limitations of photocoagulation in the treatment of diabetic maculo-foveolar edema: macular neuro-epithelium detachment]. PMID- 2257646 TI - [Diabetic retinopathy and cataract]. PMID- 2257647 TI - [Limitations related to environmental conditions in the laser treatment of diabetic retinopathy]. PMID- 2257648 TI - [Acute ischemic diabetic retinopathy]. PMID- 2257649 TI - [Limitation of photocoagulation in diabetic neoproliferative retinopathy as a function of the patients' age]. PMID- 2257650 TI - [Limitations related to the vitreo-retinal status in the laser treatment of ischemic diabetic retinopathy]. PMID- 2257651 TI - [Long-term results of stereoghif in diabetic retinopathy]. PMID- 2257652 TI - [Use of 90-dioptry lenses for retinal photocoagulation in diabetic patients]. PMID- 2257653 TI - [Lens complication during panphotocoagulation using a panfundoscope]. AB - We report one case of lens opacities, secondary to retinal panphotocoagulation using the panfunduscope. Cataract can be attributable to nuclear sclerosis, optical features of the panfunduscope and blue-green laser. PMID- 2257654 TI - [Krypton laser treatment of macular retinal detachment associated with optic nerve pit]. PMID- 2257655 TI - [Preservation of human corneal tissue. Limitations of K-SOL: short and intermediate term]. PMID- 2257657 TI - [The papillary index: its contribution to the analysis of physiologic excavations]. PMID- 2257656 TI - [Computer-assisted calculation of the neuroretinal rim area. Early diagnosis and surveillance of primary open-angle glaucoma]. AB - The neuroretinal rim area computation is the choice complementary overhaul in early diagnosis and watching of primitive open angle glaucoma. The interest of this overhaul are objectivity, swiftness and plainess of production. The author devised a system who measure precisely, safely and swiftly this area. For a best watching of your patients with glaucoma or suspected of having glaucoma, it's possible, with this process, to know the neuroretinal rim area of your patients. It's necessary to take a color slide of the optic nerve head (Kodachrome 64 asa, angle 45 degrees) and measure parameters on the patient (length in mm of the flashed slit on the optic nerve head with the slotted light and Goldmann lens, the measurement in dioptries of the ametropia and the radius in mm of the anterior surface of the cornea). PMID- 2257658 TI - [Ciprofloxacin: intraocular absorption in man]. AB - The intraocular penetration of Ciprofloxacin in man: authors have studied the penetration of Ciprofloxacin in the aqueous humor of 30 patients (30 eyes). The concentration in the anterior chamber was on average 0.73 mg/l which is 33% of serum level, from 1.30 hours after a single oral dose of 1000 mg till the 4th hour after this dose. The samples were assessed by a microbiological method. These results are over the minimal inhibitory concentration for many bacterial agents found in endophthalmitis. So this antibiotic may be proposed in the treatment of endophthalmitis. Anyway further investigation is mandatory to assess the safety on efficacy of these antibiotics. PMID- 2257659 TI - [Basedow's disease and atypical ophthalmologic signs]. AB - The authors report a case of BASEDOW's disease discovered with CT scan. The beginning was uncommon, characterized by orbital pains associated with optic neuropathy without any other signs of hyperthyroidism. PMID- 2257660 TI - [Intraocular lymphoma]. PMID- 2257661 TI - [Macular site of bone choristoma of the choroid]. PMID- 2257662 TI - [Quantified surgery of exotropia. Statistic analysis]. PMID- 2257663 TI - [Treatment of giant tears with inversion of the posterior flap]. PMID- 2257664 TI - [Retinal detachment caused by giant tears: recent clinical results]. AB - We perform surgery on ten eyes of ten patients of retinal Detachment with giant retinal tear. The surgical procedure induced lensectomy, vitrectomy, retinal incarceration, circumferential scleral buckling on 360 degrees, retinal tamponade with gaz (C3F8) and post-operative photocoagulation of the giant tear. Although most of cases was associated with massive proliferation vitreo-retinopathy, total retinal reattachment was achieved in five eyes. PMID- 2257665 TI - [Unilateral (7 cases), bilateral (1 case) cerebral xanthomatosis: involvement of the temporal bone alone?]. PMID- 2257666 TI - [How to follow the visual development in infants under 2 years of age]. PMID- 2257667 TI - [Syndrome of generalized ocular fibrosis]. PMID- 2257668 TI - [Risk factors of non-proliferating retinopathy in insulin-dependent diabetes]. AB - Risk factors for non proliferative retinopathy were investigated by comparing two groups of insulin dependent diabetic patients: group NR of 25 patients without retinopathy and group R of 25 patients studied at the time of discovery of non proliferative retinopathy. The two groups were matched for age, sex and diabete duration. They were significantly different for insulin treatment regimens, blood glucose control and blood pressure. Lipid parameters and renal function were similar in the two groups. PMID- 2257669 TI - [Treatment of retinal detachment complicated by severe vitreoretinal proliferation using the expansive gas, C3F8]. PMID- 2257670 TI - [Fuchs' cyclitis: etiologic and clinical aspects]. AB - 45 patients with Fuchs' heterochromic cyclitis were examined. The clinical signs and their chronological order are summarized. A possible etiological role for ocular injuries and toxoplasmosis is discussed. PMID- 2257671 TI - [Magnetic resonance imaging in the evaluation of malignant melanoma of the choroid and ciliary body]. AB - We evaluated 16 patients with malignant melanomas of the choroid (11) or the ciliary body (5) by magnetic resonance imaging (MRI), using a 0.5 T magnet and a surface coil. The tumor was seen in all cases, hyperintense in T1-weighted images, and hypointense in T2-weighted sequences (80%). These images reflected the short T1 and T2 relaxation times caused by the presence of melanin in those tumors. This non-invasive method was superior to computed tomography (70%), and sometimes superior to fundoscopy (2 cases), angiofluorography (3 cases) or echography (1 case). MRI also proved valuable for differentiating uveal melanoma from associated subretinal effusion. PMID- 2257672 TI - [Keratomycoses: practical aspects]. AB - In our daily clinical practice, keratomycosis still remain a challenge for both the ophthalmologist and the laboratory. In this paper simple advices are listed to help us, especially in the topical medical treatment. The emerging role of silver sulfadiazine is pointed out. PMID- 2257673 TI - Outcome improving for lung transplant patients. PMID- 2257674 TI - Gallstone therapy: return to the gold standard. PMID- 2257675 TI - Management of inflammatory bowel disease: 30 years of observation. AB - Management of inflammatory bowel disease has become more precise and effective in the last 30 years, ensuring long, productive lives for most patients. Data such as family history, duration of disease, the onset of complications, and type of therapy are presented from 450 patients with inflammatory bowel disease treated during a 10-year period ending in 1984. The incidence of general complications over three decades is compared. Perianal disease and intestinal obstructions dominate complications of Crohn's disease. The most common nongastrointestinal complication for patients with either disease is monarticular large joint arthritis. Approximately 75% of patients with Crohn's disease will eventually undergo surgery. In the first decade of data collection, 50% of patients with ulcerative colitis had surgery; in the second decade, 26%; and in the third decade, 39%. The changing percentages correspond initially to advances in medical therapy and then to advances in surgical therapy. PMID- 2257676 TI - Hepatic artery infusion chemotherapy for colorectal liver metastases. AB - Twenty-two patients with hepatic colorectal metastases had Infusaid pumps implanted for hepatic artery infusion chemotherapy, or HAIC. Prior to pump placement, 19 of the 22 patients received percutaneous HAIC with 5-fluorouracil and citrovorum factor. Floxuridine, 0.2 mg/kg/d, was administered via the Infusaid pump and was alternated with saline solution every 2 weeks. HAIC responsiveness was defined as a 50% or greater reduction in the sum of all diameters of measured lesions on computerized tomography scans and no evidence of extra-hepatic tumor. Nine patients (41%) had a favorable response to HAIC; four (18%) had a partial response to percutaneous HAIC and five (23%) were considered pump responders. All responders had pretreatment liver replacement of less than 50%. The mean survival after pump placement was 13.6 months for responders and 11.1 months for non-responders. Although there were no operative deaths, the morbidity rate was 36%, and 31% of patients manifested significant chemotherapy toxicity. While toxicity is not insignificant and there is no survival benefit, the Infusaid pump is a reliable drug delivery system for HAIC, and may result in regression of colorectal liver metastases in patients with less than 50% hepatic replacement. PMID- 2257677 TI - Psychological factors in men with genital pain. AB - Among 48 men with genital pain and no organic findings, psychological disorders were diagnosed frequently, including somatization disorder in 56%, nongenital chronic pain syndromes in 50%, major depression in 27%, and chemical dependency in 27%. About one third of the group were socially isolated and 18% had had an important emotional loss at the time of pain onset. Despite their mean age of 41, only half of the men were married. These data suggest that genital pain without organic findings is often related to psychological disorders, life stress, and poor social support. Treatment planning should take these factors into account. PMID- 2257678 TI - Quality in hospitals: methodology for self-appraisal and change. PMID- 2257679 TI - AIDS: challenges to our health care systems. AB - The presentation excerpted here was given at the Cleveland Clinic's Second Annual Update on the Acquired Immunodeficiency Syndrome in May 1989. At that time, the numbers herein were current. Since then, the number of reported cases of AIDS in the United States has surpassed 120,000, and includes more than 2,000 children; the number of American deaths from AIDS has exceeded those occurring as a result of the Vietnam war; and AZT has been recommended for use in both mildly asymptomatic and asymptomatic HIV-infected persons. PMID- 2257680 TI - Implications of childhood hypercholesterolemia. AB - Several studies have documented that hypercholesterolemia is common in American children. Other studies have shown that elevated cholesterol levels in childhood remain elevated well into adult life. Autopsy studies of adolescents have also found a strong positive correlation between antemortem cholesterol levels and early atherosclerotic changes in their aortas and coronary arteries. Collectively, these studies provide strong and consistent evidence that atherosclerosis begins in childhood. The evidence is also overwhelming that lowering elevated low density lipoprotein cholesterol levels reduces the risk of heart attacks caused by coronary heart disease, at least among middle-aged men. As a result, routine cholesterol and coronary heart disease risk factor surveillance in childhood is both productive and appropriate. Premature coronary heart disease may be largely preventable and atherosclerosis, if not preventable, can be significantly delayed. PMID- 2257681 TI - Oncogenes and cancer: clinical applications. AB - Oncogenes are aberrant forms of proto-oncogenes, which are normal cellular genes that participate in cell growth and development; proto-oncogenes contribute to tumor formation when mutations or chromosomal translocation cause them to escape normal controls. Anti-oncogenes, also involved in neoplasm development, normally participate in inhibition of cell growth and proliferation; they become tumorigenic when mutations alter their function. Oncogene or anti-oncogene abnormalities have been characterized for a variety of tumors, with resulting clinical applications. In some forms of leukemia, for example, determining the presence or absence of the bcr-abl gene rearrangement has both diagnostic and prognostic value. The best-studied anti-oncogene is that found in retinoblastoma. Molecular techniques can differentiate the hereditary from the nonhereditary form of this disease and, with hereditary retinoblastoma, predict disease likelihood in family members. PMID- 2257682 TI - The Canadian health care system: is our present your future? PMID- 2257683 TI - Re: Testosterone use in menopause. PMID- 2257684 TI - Re-evaluation of the plasma renin-angiotensin system in anephric patients. AB - In view of recent observations that a number of extrarenal tissues have the potential to produce angiotensin II and release it in a regulated fashion, we made measurements of immunoreactive angiotensin I (irAng I) and angiotensin II (irAng II), along with active and inactive renin, and angiotensinogen in plasma of seven anephric patients and of 16 normal healthy volunteers to gain insight into possible sources of plasma Ang II. High performance liquid chromatography clearly demonstrated that the predominant component of irAng II in anephric plasma is the biologically active octapeptide Ang II. Plasma renin activity (PRA), and active and inactive renin all were detected in all of the anephrics but their levels were decreased to 33% for PRA, 12% for active renin, and 18% for inactive renin when compared with those in healthy subjects. While plasma angiotensinogen was significantly but only slightly increased in anephric patients (+28% over the mean value for normal subjects), irAng I and irAng II both were present in quantities almost comparable with those in normals. These results suggest that local angiotensin production contributes, in part at least, to the circulating plasma Ang II. Vascular tissue seems to be the best candidate responsible for such a mechanism, on the basis of recent demonstrations of unequivocal, regulated release of Ang II from diverse vascular beds. PMID- 2257685 TI - Effects of calcium and deoxycorticosterone on blood pressure, plasma renin activity and vascular reactivity in spontaneously hypertensive rats. AB - The effects of calcium and deoxycorticosterone (DOC) on blood pressure, plasma renin activity (PRA), urinary sodium excretion and aortic responses were studied in spontaneously hypertensive rats (SHR). The animals (age 9 weeks) were divided into four treatment groups: control, calcium, DOC and DOC+calcium (n = 12 and the mean systolic blood pressure 174-177 mmHg in each). Calcium was given as 1.5% CaCl2 in drinking fluid, and DOC trimethylacetate by weekly injections (25 mg/kg s.c.). During the 4-week study systolic blood pressure rose in all groups, but the increase was attenuated by calcium (final levels: control 201 +/- 3, calcium 186 +/- 3, DOC 206 +/- 2, DOC + calcium 203 +/- 2 mmHg, mean +/- SE). PRA was reduced in both groups receiving DOC, but it was not affected by calcium. Calcium supplementation increased urinary excretion of sodium in DOC-treated animals. DOC enhanced the in vitro contractility of helically cut aortic strips to noradrenaline, and decreased the relaxation of the strips to nitroprusside and nifedipine. The results indicate that calcium supplementation attenuates the development of hypertension in SHR, and that this attenuation is not mediated by the renin-angiotensin system. DOC abolished this lowering effect of calcium on blood pressure possibly by its action on vascular smooth muscle, resulting in increased vascular contractility and impaired relaxation. PMID- 2257686 TI - Production of angiotensinogen by cultured rat aortic smooth muscle cells. AB - This study was conducted to further investigate angiotensinogen synthesis in rat aortic smooth muscle cells (SMC) grown in culture. tissue cultures maintained in defined medium neither grew nor synthesized angiotensinogen. However, in the presence of 5% homologous serum both cell proliferation and angiotensinogen synthesis became apparent. Substitution of normal control serum with that of bilaterally nephrectomized rats or animals given dexamethasone (10mg/kg, ip) led to a further significant increase in angiotensinogen production. In contrast, serum from adrenalectomized rats suppressed angiotensinogen synthesis below the rate observed with normal serum. A positive linear correlation (r = 0.96, p less than 0.01) was evident between the serum angiotensinogen level and the rate of de novo synthesis of this protein. No correlations were found between cell proliferation and either angiotensinogen synthesis or serum angiotensinogen levels. Dexamethasone added to serum did not stimulate the rate of angiotensinogen synthesis and appeared to inhibit cell proliferation. Stimulation or suppression of angiotensinogen synthesis was not accompanied by a statistically significant change in angiotensinogen specific mRNA. The data indicate a complex regulation of angiotensinogen in vascular smooth muscle cells in culture. PMID- 2257687 TI - Genetically altered brain amino acid metabolism in spontaneously hypertensive rats: a study by using young spontaneously hypertensive rats and renal hypertensive rats. AB - Previously we demonstrated altered amino acid levels in brainstem regions of adult spontaneously hypertensive rats (SHR). For comparison, in this study, we determined amino acid concentrations in discrete brainstem regions in young prehypertensive SHR and renal hypertensive rats. In prehypertensive SHR, the content of glutamate was increased in the rostral ventrolateral medulla and the caudal ventrolateral medulla, and the content of beta-alanine was decreased in the nucleus tractus solitarii. In renal hypertensive rats, there was no change in glutamate and beta-alanine contents in all the regions. The profiles of contents of glutamate and beta-alanine in the brainstem regions in young SHR but not in renal hypertensive rats are the same as those found previously in adult SHR. Thus, the results of the present study suggest that the altered amino acid metabolism in the brainstem of SHR may be genetically inherent. PMID- 2257688 TI - Kinetics of red cell Na+ and K+ transport in Prague hypertensive rats. AB - Kinetics of ouabain-sensitive, furosemide-sensitive (FS), bumetanide-sensitive (BS) and -resistant Na+ and K+ transport were studied in erythrocytes of Prague hypertensive rats (PHR) and Prague normotensive rats (PNR). Maximal transport rates (Vmax) and apparent affinities for either intracellular Na+ or extracellular K+ (replaced by Rb+) were determined in red cells in which Na+ content varied around the physiological range and that were incubated in Na+ media. No major differences between PHR and PNR were disclosed in the kinetics of ion transport mediated by the Na(+)-K+ pump or BS inward Na(+)-K+ cotransport. FS Rb+ uptake was higher (due to a greater Vmax) in red cells of PHR as compared to PNR. In cells with a lowered Na+ content this elevation of FS Rb+ uptake was largely due to an augmented K(+)-Cl- cotransport which exhibits a low affinity for Rb+o and is blocked by 1 mM furosemide but not by 10 microM bumetanide. Red cells of PHR and PNR strains did not differ in either Na+ or Rb+ leaks. A slight increase of red cell Na+ content in PHR was evaluated in terms of the pump-leak concept. The present study did not reveal any obvious kinetic abnormalities of red cell cation transport the presence of which in tissues involved in blood pressure regulation would favor the development or the maintenance of genetic hypertension in PHR. PMID- 2257691 TI - Poster abstracts from the 1989 Journees de L'Hypertension Arterielle. PMID- 2257689 TI - Alteration in the sarcolemmal Na(+)-K+ pump of hindquarters resistance arteries in DOCA-salt rats. AB - It has been suggested that a circulating inhibitor of the Na(+)-K+ pump contributes to the development and maintenance of DOCA-salt hypertension. However, the discordant results have been reported as to whether the sarcolemmal Na(+)-K+ pump in DOCA-salt hypertension is inhibited. Furthermore, no study has examined alteration in the sarcolemmal Na(+)-K+ pump of the true resistance arteries. We examined hindquarters vasoconstriction induced by ouabain (10(-3) M) in the vascularly isolated hindquarters of the DOCA-salt treated or control rats, which were perfused with Krebs-Henseleit solution. Hindquarters vasoconstriction induced by ouabain (10(-3) M) was greater in the prehypertensive and hypertensive DOCA-salt rats than in the corresponding control rats (p less than 0.01). We also examined hindquarters vasoconstriction induced by ouabain (10(-3) M) in the vascularly isolated hindquarters of the normal assay rats which were perfused by the plasma obtained from the DOCA-salt or control rats. The plasma of the prehypertensive and hypertensive DOCA-salt rats attenuated ouabain-induced hindquarters vasoconstriction in the assay rats (p less than 0.01). The plasma of the DOCA-salt rats did not alter nonspecific vasoconstriction caused by barium chloride. These results suggest that the plasma of the prehypertensive and hypertensive DOCA-salt rats had an inhibitor of the sarcolemmal Na(+)-K+ pump of the resistance arteries, but the sarcolemmal Na(+)-K+ pump molecules of the resistance arteries of those rats were increased. The in vivo activity of the sarcolemmal pump of the resistance arteries of the DOCA-salt rats would be determined by the relative influence of increased pump molecules and a circulating pump inhibitor. PMID- 2257690 TI - Effect of dietary calcium on in vitro aortic tissue responsiveness to a hypertensive factor. AB - It has been proposed that calcium supplementation in the diet is associated with a reduction in blood pressure. In the present study, we investigated vascular tissue sensitivity to a hypertensive factor (HF) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high calcium diet, a low calcium diet and a food restricted diet. HF, which has been isolated from erythrocytes, increases blood pressure when injected into normotensive rats and stimulates calcium uptake by aortic rings in vitro. Five-week-old rats were divided into the following groups: SHR and WKY fed a regular diet (1% calcium), SHR and WKY fed a high calcium diet (4% calcium), SHR and WKY fed a low calcium diet (0.02% calcium) and SHR and WKY fed a regular diet (1% calcium) in which food intake was restricted to 65% of ad libitum intake. Food intake, body weight, urine phosphate excretion and blood pressure development were followed for 8 weeks. At sacrifice, plasma levels of calcium and phosphate were determined. Tissue responsiveness to HF was calculated by incubating aortic rings from the rats in the different groups with HF and measuring lanthanum-resistant calcium uptake. A 4-fold increase in dietary calcium reduced blood pressure and tissue responsiveness to HF in SHR. Neither parameter was affected by the high calcium diet in WKY. The low calcium diet had no effect on either blood pressure or tissue responsiveness to HF in SHR or WKY. Restriction of food intake induced a reduction in blood pressure and in tissue responsiveness to HF in SHR. It did not affect the same parameters in WKY. The results suggest that the increased tissue responsiveness to HF in the SHR may be associated with high blood pressure. PMID- 2257692 TI - Inflammatory products of commensal bacteria and gastro-intestinal disorders. PMID- 2257693 TI - Gastrointestinal side effects of the nonsteroidal anti-inflammatory drugs. PMID- 2257694 TI - Epidemiological evidence on coffee and digestive tract cancers: a review. PMID- 2257695 TI - Pyogenic liver abscess: a review of aetiology, diagnosis and intervention. PMID- 2257697 TI - Neonatal necrotising enterocolitis. An update. PMID- 2257696 TI - Solitary rectal ulcer syndrome: aetiology, investigation and management. PMID- 2257698 TI - Immunologic evidence for the in situ deposition of a cytoplasmic streptococcal antigen (endostreptosin) on the glomerular basement membrane in rats. AB - Endostreptosin (ESS) is an antigen derived from the cytoplasm and the plasma membrane of nephritogenic group A and to a lesser extent group C and G streptococci. It is immunologically not related to streptococcal exoenzymes or the streptococcal cell wall and can be detected on the endothelial side of the glomerular basement membrane of kidney biopsies of patients with acute poststreptococcal glomerulonephritis (ASGN) during the early phase of the disease. Highest and most persistent antibody titers to this antigen are found in patients with ASGN. Immunoaffinity isolated ESS was injected i.v. into the tail vein of Wistar Furth (W/FU) rats for up to five successive days. The animals were sacrificed on days 1, 2, 3, 4, 5, 8, 9, 10, 11 and 12. Frozen sections of the rat kidneys were tested by immunofluorescence against rabbit anti-ESS-antibody and against sera from patients who had recently recovered from ASGN as well as against anti-rat-IgG and C3. The basement membranes of rat kidneys were positive for ESS deposition starting from day one on, but were negative for anti-rat IgG and C3 during the first four days. Rats sacrificed on days 8-12 showed increasing deposition of IgG and C3 with decreased staining for ESS. The sera of rats sacrificed on days 1-3 had no detectable anti-ESS antibodies; whereas animals from day 4 on had low levels of anti-ESS antibodies as determined by microcomplement fixation. Control animals showed no staining for ESS, IgG, C3 as well as no detectable anti-ESS antibodies. PMID- 2257699 TI - Decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis (APSGN). AB - In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr labelled platelets. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet times survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction. PMID- 2257700 TI - Postpartum renal failure in systemic lupus erythematosus. AB - The present report describes an unusual association between postpartum renal failure and systemic lupus erythematosus. Two healty young women developed progressive renal failure several weeks after delivery accompanied by the presence in their serum of strongly reactive anti-nuclear antibodies and positive anti-DNA antibodies. In both cases kidney biopsy disclosed light and electron microscopy pictures typical of idiopathic postpartum renal failure, with multiple intravascular thrombi and no evidence of active lupus nephritis. Intrarenal microthrombi formation may represent a form of exacerbation of systemic lupus erythematosus after delivery. The early recognition of this syndrome may have therapeutic implications. PMID- 2257701 TI - Hemolytic uremic syndrome in patients with Behcet's disease treated with cyclosporin A: report of 2 cases. AB - Hemolytic uremic syndrome (HUS) has been reported in patients treated with cyclosporin A (CsA) following bone, hepatic and kidney transplantation. We report two patients with Behcet's disease (BD) under CsA treatment because of severe uveitis, who developed HUS several months after the initiation of treatment. Renal biopsies showed lesions consistent with the diagnosis of the arterial form of thrombotic microangiopathy: vascular thrombosis with extensive glomerular ischemia. Renal failure persisted after withdrawal of CsA: one patient is in chronic renal failure (CRF) with a 4-year follow-up; the other died after refusal of chronic hemodialysis. In our two patients, excessive doses of CsA with high trough levels are likely to have contributed to the development of HUS. A rapid adjustment of CsA doses and an early detection of signs of the microangiopathic process might have prevented this severe complication of CsA treatment. PMID- 2257702 TI - Incidence and etiology of hyponatremia in an intensive care unit. AB - To evaluate the incidence and causes of hyponatremia in intensive care unit (ICU) patients, retrospective and prospective studies were done. Hyponatremia was defined as a serum sodium concentration equal to or less than 134 mmol/l (134 mEq/l). Prospectively, 29.6% of patients displayed hyponatremia. Relevant data were obtained in twelve patients. Two patients did not have serum hypoosmolality. In the ten patients with serum hypoosmolality, urine osmolality was not maximally dilute and urine sodium concentration was greater than 30 mmol/l (30 mEq/l) suggesting inappropriate antidiuretic hormone secretion (SIADH). However, three patients exhibited suppressed ADH levels despite absence of maximal urinary dilution. The data suggest that hyponatremia is common in ICU patients and that renal diluting defects are frequent. Therefore, hypotonic fluid should be administered cautiously. PMID- 2257703 TI - Knowledge of hemodialysis and CAPD patients about their prescribed medicines. AB - A questionnaire was designed to determine and compare the extent of knowledge of 40 continuous ambulatory peritoneal dialysis (CAPD) and 40 hemodialysis (HD) patients about their medicines. It was administered orally to outpatients attending a clinic by an investigator unknown to the patients. Data were collected pertaining to the following target drugs: calcium supplements, phosphate binders, vitamins B and C and folic acid. HD and CAPD groups were closely matched for age and sex. Sixty percent of CAPD and 49% of HD patients were taking four or more medications. The dose of folic acid was accurately recalled by 91% and 71% of CAPD and HD patients. Indications for calcium supplements and phosphate binders were known by only 8% and 30% of CAPD patients compared to 72% and 73% of HD patients. More HD patients knew the indications for all target drugs (p less than 0.01). More CAPD than HD patients knew the expected duration of therapy (p less than 0.01). There was a trend between decreased knowledge of whether the medication was working with increasing age of CAPD patients. Most drug information was supplied by physicians, but many CAPD patients (21%) obtained information from lay sources. When given the opportunity to ask questions about their medicines, only 56% CAPD and 46% HD patients did so. The knowledge of CAPD and HD patients studied was grossly deficient in terms of indications, effectiveness, duration and action to be taken if doses were missed. PMID- 2257704 TI - Autologous implant of peritoneal mesothelium in rabbits and man. AB - With the purpose of studying peritoneal physiology, original biopsy methods were devised and human and rabbit peritoneal mesothelial cells cultured and characterized. It was then decided to verify whether these cells could be implanted autologously during peritoneal dialysis in cases of acute loss of mesothelial surface. Staphylococcal peritonitis was induced in 12 rabbits and after 4 days of antibiotics, 6 of them were autoimplanted with cultured mesothelial cells, previously marked in 3 cases with thymidine (H3TdR). Implanted rabbits sacrificed after 3 and 6 days showed taking of the new mesothelial cells both by direct morphological observation and by autoradiography. Four uremic CAPD patients recovering from severe peritonitis were implanted with 300 million of their own peritoneal mesothelial cells, previously cultured and frozen. Morphological signs of taking were evident by laparoscopy and from peritoneal biopsies performed 3 and 6 days after implant. The fact that such implants are possible may have interesting applications in medicine and surgery. PMID- 2257705 TI - Blood cells and red cell morphology in the urine of healthy children. AB - The count of blood cells and the morphology of red cells in urine has been widely used in adult medicine to aid in the diagnosis of the etiology of hematuria. The normal ranges for blood cells in the urine of children had not been established previously. The urine of 419 healthy children was studied. Urine of 95% of individuals contained less than 14 x 10(6) red cells per liter. The morphology of these red cells was of a glomerular pattern. Red cells of non-glomerular pattern were not seen in the urine of healthy children. Urine of 95% of children contained less than or equal to 4 x 10(6) leukocytes per liter. PMID- 2257706 TI - Hypertrophic cardiomyopathy evolving into a hypokinetic and dilated left ventricle: coronary embolization as a probable pathogenetic mechanism. PMID- 2257707 TI - Unstable angina: early management. PMID- 2257708 TI - Unstable angina pectoris. AB - The pathophysiology of unstable angina has been better elucidated in the past five years and has led to more rational therapy. Coronary arteries in patients with unstable angina have atherosclerotic plaques which are often complex and are the site of platelet activation and fibrin deposition. Nitrates, one of the oldest therapies, are efficacious and act not only by dilating coronary vessels but by reducing preload and afterload. Beta blockers have a salutary effect by decreasing myocardial oxygen demand. Calcium channel blockers attenuate smooth muscle contraction and thereby act to decrease coronary artery spasm. Beta blockers and calcium channel blockers are equally efficacious in unstable angina. The antiplatelet agent, aspirin, has been shown to reduce fatal or non-fatal myocardial infarction and probably overall mortality. The use of heparin acutely for unstable angina has been demonstrated to decrease refractory angina and myocardial infarction, and acutely is probably better than aspirin. For patients with reduced ejection fractions (0.30-0.49), a prospective randomized trial has shown that coronary artery bypass graft surgery offers an improved three-year survival compared with medical therapy; however, surgery does not prevent myocardial infarction. Percutaneous transluminal coronary angioplasty may be a reasonable therapeutic alternative for some patients with single-vessel disease who are refractory to medical therapy but there are as yet no controlled trials of this question. To date a clinical benefit from thrombolytic therapy has not been demonstrated. PMID- 2257709 TI - Temperature monitoring during peripheral thermo-optical laser recanalization in humans. AB - To determine probe temperature required to achieve laser thermal recanalization of human peripheral arteries, temperature was monitored at the probe tip using a K-type thermocouple and displayed on a computer screen in real-time in 21 procedures. Recanalization was performed using a Spectraprobe-PLR delivering both laser light and heat in patients with prolonged ischemic limb symptoms. Laser recanalization of totally occluded peripheral arteries (occlusion length = 5.3 +/ 3.8 cm) was done percutaneously (17 procedures) or intraoperatively (4 procedures), after unsuccessful attempts of recanalization using standard guide wire and balloon angioplasty techniques. Probes were activated using argon laser irradiation starting at 5 W and increased by 1-W increments until successful recanalization, or up to a maximum of 12 W. Laser recanalization was achieved in 16/21 (76%) procedures at a mean temperature of 178 +/- 120 degrees C (range 64 503 degrees C) and a mean time of 12.4 +/- 14.1 s. Eleven of the 16 (69%) recanalizations occurred at probe temperature lower than 160 degrees C. Recanalization was achieved at a mean power of 7 +/- 2 W. Perforation occurred in 6 arteries at peak probe temperatures ranging from 73 to 502 degrees C. Perforations occurred in 4 of 6 densely calcific vessels which required high probe temperatures (greater than 250 degrees C). An important feature of temperature monitoring was the immediate detection of probe dysfunction. Although recanalization temperature had a wide range, the majority of recanalizations occurred at probe temperature below 160 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257710 TI - Late potentials recording with a precordial signal-averaged electrocardiogram in 53 consecutive patients with a first acute myocardial infarction: incidence and early natural history. AB - Signal-averaged electrocardiograms were obtained in 53 consecutive patients with a first acute myocardial infarction (AMI) who survived the first 10 days of hospitalization. The recording was performed twice, at Day 1 and at Day 10 of hospitalization, in patients without bundle-branch block and who did not receive antiarrhythmic therapy. Signal-averaged ECGs were obtained with an instrument which analyzes the presence of late potentials (LP) in each individual precordial lead. There were 41 men and 12 women, mean age of 67 years. On Day 1, three patients had LP (5.6%). On Day 10, LP was recorded in 11 patients (21%). In only one patient was LP transient. Patients who developed LP by Day 10 (absent in Day 1) had statistically significant lower root mean square (rms) voltage and higher QRS duration than patients who did not develop LP on Day 10. In conclusion, in patients with a first AMI who survive the initial hospitalization period and are not in need of antiarrhythmic therapy have an incidence of LP of 21%. A predischarge recording is preferable since this will maximize the chances of detecting LP. PMID- 2257711 TI - Ergonovine maleate test detects anginal patients with poorly reproducible exercise tests. AB - The aim of the study is to evaluate the reproducibility of exercise testing and to determine whether there is any correlation between the reproducibility of exercise test and response to the ergonovine maleate test. Thirty-eight patients with mixed angina and documented coronary artery disease underwent an ergonovine maleate test and four exercise tests on consecutive days in the same basal conditions. The ergonovine test was positive in 20 patients (Group I) and negative in 18 patients (Group II). There were no significant differences in the clinical and angiographic data of the two groups. All 152 exercise tests were positive. The variability of the response of the repeated tests was assessed by means of an analysis of the following parameters: heart rate, blood pressure, rate-pressure product, watts, and minutes were recorded at the onset of ischemia (ST decreases greater than or equal to 0.1 mV). Range (maximal-minimal obtained value), ratio between range and maximal obtained value, and coefficient of variation (standard deviation/mean of the four parameters) were calculated for each patient. The analysis of these values demonstrated that while the test was reproducible in some patients, a high individual variability was present in others. Moreover, the individual variability results were higher in Group I than in Group II, with a statistically significant difference for all considered parameters. In conclusion, it is possible to have a poorly reproducible exercise test in patients with mixed angina. The correlation between a positive ergonovine test and a poorly reproducible exercise test suggests that abnormal coronary vasomotion may sometimes be present during exercise and may affect the reproducibility of the test. PMID- 2257712 TI - Quinidine treatment of chronic lone atrial fibrillation. AB - Patients with chronic lone atrial fibrillation (LAF) were treated with quinidine according to a special schedule to establish sinus rhythm and prevent recurrences. Twenty-seven patients following this schedule were identified retrospectively. To prevent relapses, quinidine had been continued in 25 patients in doses 100 mg quid lower than those used for conversion. In 8 of the latter group, quinidine had to be discontinued or reduced. All patients converted to sinus rhythm. If well tolerated, quinidine prevented recurrence of LAF in 75% of those on long-term (mean follow-up 3.5 years) prophylaxis. After discontinuation of quinidine in 8 patients, LAF recurred in all but one patient. Side effects were observed in 22% of the patients and precluded continuation of the prophylaxis in 15%. No incidence of torsade de pointes was encountered. PMID- 2257713 TI - Doppler assessment of interventricular pressure gradient across isolated ventricular septal defect. AB - Continuous wave Doppler ultrasound was used to estimate the pressure gradient between the right and left ventricle for assessment of pulmonary arterial systolic pressure in 30 patients with isolated ventricular septal defect and for subsequent comparison with similar data obtained on cardiac catheterization. The age of the patients ranged from 8 months to 45 years (6.8 +/- 8.6 years). No patient had right or left ventricular outflow tract obstruction. Doppler measurements were done within 24 h of cardiac catheterization. Pressure gradient across ventricular septal defect on cardiac catheterization ranged from 7 to 95 mmHg (48 +/- 24 mmHg) and that on Doppler assessment ranged from 8 to 78 mmHg (42 +/- 20 mmHg). Doppler measurements of interventricular pressure gradient correlated well with those obtained on cardiac catheterization (r = 0.90, p less than 0.001). Correlation was better in patients with pressure gradient across ventricular septal defect less than 75 mmHg (r = 0.96). Correlation was poor in three of five patients with very small ventricular septal defects (interventricular pressure gradient greater than 75 mmHg) because the jet used was not ideal. Thus continuous wave Doppler ultrasound is an accurate noninvasive means of measuring pressure gradient across ventricular septal defect, which is a useful parameter for assessment of pulmonary artery systolic pressure in patients with isolated ventricular septal defect without right and left ventricular outflow tract obstruction. PMID- 2257714 TI - Do antiarrhythmic drugs work? Some reflections on the implications of the Cardiac Arrhythmia Suppression Trial. AB - Despite major advances in our understanding of the mechanisms of cardiac arrhythmias and how antiarrhythmic drugs appear to work, there remains much doubt whether these agents reduce arrhythmic mortality except in certain subsets of patients. The results of the Cardiac Arrhythmia Suppression Trial (CAST) have indicated that certain antiarrhythmic drugs not only "fail to work" but may substantially increase mortality. The effects of Class Ic agents in CAST and the meta-analysis of randomized antiarrhythmic trials in the survivors of acute infarction suggest that drugs that act primarily by delaying conduction are particularly deleterious in the survivors of acute infarction. Whether these data have a wide applicability in terms of all ventricular arrhythmias is unclear, but beta-blockers remain the only class of agents that in control trials have been shown to reduce sudden death. The effect appears to be related to beta-blockade and not to suppression of premature ventricular contractions (PVCs). Beta blockers appear to act by preventing ventricular fibrillation. It is reasonable to assume that PVC suppression per se is unlikely to produce a reduction in sudden death. Uncontrolled data with amiodarone suggests that it has the potential to prolong survival by controlling arrhythmias. The effects of amiodarone and beta blockers, both significantly attenuating adrenergic stimulation, provide pharmacologic probes to define the crucial determinants of efficacy of a compound for mortality reduction in high risk survivors of myocardial infarction. The focus must now shift from antiectopic and antiarrhythmic agents that delay conduction to those that exert antifibrillatory actions by sympathetic antagonism and those that exhibit the added property of lengthening myocardial refractoriness. PMID- 2257715 TI - Left ventricular free wall rupture following acute myocardial infarction and cardiac amyloid. AB - A 74-year-old man died of left ventricular free wall rupture 6 days following an acute inferoposterior wall myocardial infarction. His hospital course was complicated by pump failure which proved resistant to inotropic support, diuresis, and percutaneous transluminal coronary angioplasty. At necropsy, extensive amyloid deposition was noted. This case constitutes an unusual clinical setting for myocardial rupture because of the severity of systolic left ventricular dysfunction as well as cardiac amyloidosis. PMID- 2257716 TI - Ventricular tachycardia and ventricular aneurysm due to unrecognized sarcoidosis. AB - Cardiac involvement due to sarcoidosis is well recognized. Arrhythmias have been recognized in up to 50% of patients who have cardiac involvement. We report on two patients with no systemic manifestations of sarcoidosis who presented with refractory ventricular tachycardia. Evaluation demonstrated atypical left ventricular "aneurysms" with normal coronary arteries. Surgical pathology demonstrated granulomas consistent with sarcoidosis. Despite extensive surgical resection, they continued to have symptomatic ventricular tachycardia requiring implantation of a defibrillator. Recognition of sarcoidosis as an etiology for ventricular tachycardia and aneurysm is important for possible avoidance of surgery. PMID- 2257717 TI - Richard J. Bing: point and counterpoint in medicine and music. PMID- 2257718 TI - Factors determining the response to angiotensin-converting enzyme inhibitors in hypertension. AB - Converting enzyme inhibitors, alone or in combination, are a safe and effective treatment for many hypertensives. However, the range of responses varies between individual patients and it has been claimed that there are two or three phases to the response. Pretreatment plasma renin (as an indication of activation of the renin angiotensin system) and the patient's age have been claimed to predict blood pressure fall. We have investigated whether these factors are useful indications of clinical response in mild-moderate essential hypertension. We have also investigated how well the response to the first dose correlates with the response to long-term (6 weeks) treatment. In a placebo-controlled trial of enalapril (20 mg daily), the blood pressure fall was analysed using an integrated pharmacokinetic/dynamic model of the concentration-effect relationship. The relation between the active drug concentration and blood pressure fall was best described by a non-linear Langmuir (Emax) model: E = (Emax C/C50 + C), where E is the effect, C the drug concentration, Emax is the maximum blood pressure fall and C50 is the drug concentration which causes a fall in blood pressure of 50% of the maximum. For a group of 13 essential hypertensives Emax was 46/20 mm Hg and C50 77 +/- 17 ng/ml. Emax was not related to age or pretreatment renin, but was positively correlated with pretreatment blood pressure (r = 0.69; p less than 0.01). Emax after 6 weeks of treatment (48 +/- 22 and 50 +/- 20 mm Hg, respectively, r = 0.89; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257719 TI - Focus on angiotensin-converting enzyme inhibition. Satellite meeting at the 23rd annual scientific meeting of the European Society for Clinical Investigation. Athens, April 19-22, 1989. Proceedings. PMID- 2257720 TI - Angiotensin-converting enzyme inhibition in patients with essential hypertension. AB - The antihypertensive action of angiotensin-converting enzyme (ACE) inhibitors may be related to inhibition of systemic and local vascular angiotensin-II formation, to a potentiation of the local vascular kinin system with secondary stimulation of prostacyclin synthesis, and also to their effects on the central nervous system as well as on renal hemodynamics and excretory function. More detailed studies in patients with severe hypertension, previously not adequately controlled by conventional therapy with a diuretic, a beta-blocking agent and a vasodilator dihydralazine, showed that addition of the ACE inhibitor ramipril normalized systolic and diastolic blood pressure (BP) without hypotensive episodes or reflex tachycardia. ACE inhibition caused a change in the baroreceptor set point as we had previously demonstrated in healthy subjects, but baroreceptor sensitivity was not affected and the pressure response to exogenous norepinephrine remained unchanged by ACE inhibition. Despite the significant reduction in BP in our patients, endogenous creatinine clearance remained unaltered. Furthermore, the decrease in BP is accompanied by an initial natriuresis probably contributing to the BP-lowering effect of ACE inhibitors. Decreased proximal tubular reabsorption may include enhanced urate clearance reflected by a decrease in serum urate concentration which we observed despite continuous diuretic treatment. ACE inhibition also prevents secondary aldosteronism and thereby avoids renal potassium loss. In our patients this resulted in a 10% decrease in urinary potassium excretion and a small rise in serum potassium concentration. Redistribution of intrarenal blood flow with increased medullary flow, in addition, will antagonize the hydroosmotic effect of vasopressin, thus resulting in a rise in free-water clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257721 TI - Angiotensin-converting enzyme inhibition in renal and hypertensive disorders. AB - Angiotensin-converting enzyme (ACE) inhibitors have been available for about 10 years for the treatment of various forms of hypertension. Essential hypertension responds particularly well to the administration of this group of drugs, especially when combined with diuretics. A pronounced fall in blood pressure can be achieved in renovascular hypertension with high plasma renin levels; when ACE inhibitors were administered in diagnosed renal artery stenosis there was a significant rise in plasma renin activity on the affected side. Renoparenchymatous hypertension and hypertension in diabetes mellitus can also be improved by the long-term administration of ACE inhibitors, and the progression of renal failure in these disorders seems to be slowed down. Side effects such as neutropenia, exanthema, hearing disorders and pronounced hypotension with an acute deterioration in renal function are substance- and dose-dependent; regular monitoring of the patients greatly reduces their occurrence. PMID- 2257722 TI - Kinin-related effects of angiotensin-converting enzyme inhibition. AB - Angiotensin-I-converting enzyme (ACE) converts angiotensin-I to angiotensin-II and splits bradykinin into inactive fragments. Inhibition of that enzyme attenuates kinin degradation and potentiates the action of kinins in many pharmacological investigations. Kinins are very potent vasodilating peptides which reduce blood pressure by lowering peripheral vascular resistance. Under experimental conditions in vitro kinins mediated a lot of metabolic and hemodynamic effects of the ACE inhibitors. However, it is still not known whether kinins also play a major role in the blood pressure-lowering effect of ACE inhibitors in vivo. New and highly specific assays are available to determine kinins in blood. But after ACE inhibition no homogeneous changes in circulating kinins are observed by reviewing recently published studies and even inhibition of kallikrein-kinin systems by either antibradykinin-antiserum or aprotinin does not clarify the role of kinins in the hemodynamic responses to ACE inhibition. The newly available bradykinin receptor antagonists inhibit in vitro and in vivo the effect of exogenous bradykinin. They were metabolized like kinins and in higher doses can develop kinin-like activities. After intravenous injection the bradykinin-receptor antagonists induce in vivo an increase in systemic blood pressure and thereby can reduce the blood pressure-lowering effect of ACE inhibitors markedly. However, it is unclear to date whether the bradykinin receptor antagonists developed their blood pressure-enhancing effect only by blocking the kinin-induced vasodilation or by some other stimulating effects on the vasopressor hormones. As long as the mechanisms of the hemodynamic action of the bradykinin antagonists are uncertain, no unequivocal interpretation of the results is possible and the role of kinins in the action of ACE inhibitors in vivo remains still uncertain. PMID- 2257723 TI - Perspectives on the homeless mentally ill. PMID- 2257724 TI - Mental illness in the homeless: problems of epidemiologic method in surveys of the 1980s. PMID- 2257725 TI - Homeless mentally ill patients in the community: results of a general hospital emergency room study. AB - Previous inattention to the specific circumstances of homeless mentally ill individuals in general hospital settings is discussed. Homeless mentally ill individuals who presented for emergency psychiatric care in a public general hospital setting exhibited distinctive patterns of service utilization and showed evidence of being a uniquely disabled, rootless, and impoverished subgroup of mentally ill individuals. The characteristics of homeless users of general hospital psychiatric services may provide some important clues to system-wide deficits in community-based care for the members of this population. PMID- 2257726 TI - Who are the homeless families? Characteristics of sheltered mothers and children. PMID- 2257727 TI - The homeless mentally ill and community-based care: changing a mindset. AB - The care of persons with severe, persistent and disabling mental illness has received increasing attention during the past ten years. This focus is due, to some extent, to the increased visibility of a subset of this population, the large number of individuals with psychiatric problems who have become homeless. These men and women, who are without homes or in temporary residences, present a sophisticated array of needs and a multiplicity of problems which have rendered most communities impotent to provide appropriate and adequate rehabilitative services. To date, there is no "perfect" community-based system of care for these men and women. What exists is a hodge-podge of shelter, outreach and drop-in center services. Most of these provide little more than a bed (or a chair) to sleep on, a hot meal and refuge from inclement weather. This article discusses some of the issues and assumptions that inhibit and foster the development and provision of a comprehensive system of community-based care for persons with serious and persistent mental disorders who have become homeless. A framework, useful in reconceptualizing the clients, the services and the interaction between them is presented. PMID- 2257728 TI - Withdrawal from the homeless mentally ill. PMID- 2257729 TI - Some clinical approaches to the homeless mentally ill. AB - Clinicians who work with homeless people are likely to encounter a very broad spectrum of mental disorders and residential patterns. As with any other patient population, the particulars of clinical interventions must be guided by the specific constellations of biological, psychological, and social needs. However, for individuals who not only suffer from serious psychiatric disorders, but are also homeless, effective approaches may require significant modifications of traditional techniques and changes in the prioritization, timing, and framing of specific interventions. In this article we will focus on people who are severely and persistently mentally ill and who have been sleeping for months or years in shelters or in public spaces such as parks, streets, and bus terminals. PMID- 2257730 TI - Rapid detection of spatial pattern by Fourier analysis. AB - Fast Fourier transform analysis can be used to accurately and rapidly detect pattern in large two-dimensional arrangements of points, such as the locations of cells in culture or plants in a unit square. We present here a sample study of pattern in spatial random point processes. This is evidently the first time that Fourier transform-based cross-correlation techniques have been applied to the analysis of point processes of biological origin. Radial profiles of the power spectra and autocorrelation estimates revealed a nearly constant interpore distance of 0.49 +/- 0.04 mm in the locations of eccrine gland pores on the surface of human skin. Additionally, gland-free areas may exist near hair follicles. PMID- 2257731 TI - Algorithms for the computation of spatial statistics. AB - Algorithms are described for the calculation of spatial statistics. The statistics are the functions K(t), G(y), F(x), and K12(t). They can be used to determine (a) which type of spatial process ('random', 'clustered', 'regular', etc.) best fits a data set and whether the spatial pattern changes with distance, and (b) whether two types of events are correlated with each other, and if so, at which distances the correlation occurs. These functions provide a powerful tool for analysing the spatial distribution of biomedical and biological phenomena. An interactive, command-driven program that incorporates these algorithms is described. PMID- 2257732 TI - A graphical and statistical method for investigation of time series in chronobiology according to the cosinor procedure. AB - The mathematical and statistical analysis of biological time series is complex. In view of the necessity to deal with non equidistant data to analyse biological variables, preference is often given to the "cosinor procedure". We propose here a graphical and statistical assistance program for single or multiple cosinor procedure applicable to time series in chronobiology. This program investigates whether a cosine function or a mixture of cosine functions describe the experimental data adequately. The computer program is illustrated on data which have been published in a preceding paper. PMID- 2257733 TI - A computer program for the derivation of non-parametric reference ranges from patients' results. AB - A computer program to derive the reference range from patients' results is presented. It separately modifies the two halves (separated by the peak) of the frequency distribution curve of patients' results by extending a para-apical portion by linear regression and thus derives the frequency distribution curve representing results unaffected by disease. The reference range is then calculated non-parametrically. The ranges obtained for most of the common chemistries were very close to the ones in use in the laboratory. Advantages and limitations of the method are discussed. PMID- 2257734 TI - A note on the use of the intraclass correlation coefficient in the evaluation of agreement between two methods of measurement. AB - The intraclass correlation coefficient (rI) has been advocated as a statistic for assessing agreement or consistency between two methods of measurement, in conjunction with a significance test of the difference between means obtained by the two methods. We show that neither technique is appropriate for assessing the interchangeability of measurement methods. We describe an alternative approach based on estimation of the mean and standard deviation of differences between measurements by the two methods. PMID- 2257735 TI - Organization and management of a database in the respiratory physiology. AB - In this paper we present a set of programs resulting in a management system for a Database in experimental medicine. The programs are written in Fortran and they run in a VAX 8200 of DEC. We have successfully applied this management system in the study of mechanics and of the electrical activity of the muscles of the respiratory apparatus. However, it may be used in other fields of experimental medicine since it has been structured in such a way as to be easily adapted; in addition it may run in other computers. PMID- 2257736 TI - Robust logistic discriminant functions in diagnosing chronic obstructive airways disease. AB - The paper gives a comparison of the classical logistic discriminant function, the alpha-trimmed logistic discriminant function and the L1-logistic discriminant function as used for assistance of medical diagnosis in chronic obstructive airways disease. The robustified logistic discriminant functions enable one to obtain higher rates of correctly classified individuals, especially the L1 logistic discriminant function should be recommended. PMID- 2257737 TI - Computer-aided diagnosis and treatment of malaria: the IMEX system. AB - IMEX is a prototype Integrated Malaria EXpert system whose practical objectives are to act as a tool to assist medical personnel in the diagnosis and treatment of malaria, to improve management of malaria patients and to formalize and document knowledge on malaria. This paper describes some of its important features, both from the user's point of view, as well as the technical aspects. The design of IMEX has taken into account practical considerations like cost, ease of usage and integration with its working environment. An evaluation of IMEX and some enhancements which can be made to the prototype are also discussed. PMID- 2257738 TI - A protein assay program for Lotus 1-2-3. AB - Protein assays have become a widespread procedure not only in biochemistry but in many disciplines. This paper describes a program that takes advantage of the capacity of a spreadsheet program such as Lotus 1-2-3 to produce a graph and perform the calculations necessary for such assays. Its simplicity allows users with little or no experience with Lotus 1-2-3 to run it once installed. PMID- 2257739 TI - A randomized trial of the Gyne T 380 and Gyne T 380 Slimline Intrauterine Copper devices. AB - To facilitate manufacture and insertion of the Gyne T 380 IUD, design changes were instituted. Copper collars were seated flush at the ends of the horizontal crossbar of the device. A randomized study of the Gyne T 380 Slimline, the new design, was undertaken in comparison with the standard Gyne T 380. A total of 996 women were enrolled, with 698 Slimline insertions and 298 of the standard Gyne T. No statistically significant difference in ease of insertion or in performance was detected between the models. At one year, the pregnancy rate of each model was below 0.5 per 100 and the continuation rate was 79-80 per 100. Pelvic inflammatory disease or endometritis was found in one percent of subjects in the first year. This is the seventh multicenter randomized study of a collared T IUD with 380 mm2 of copper surface. In all seven, the one-year gross pregnancy rate has been 1.2 per 100 or lower. PMID- 2257740 TI - A randomized comparative study of the performance of seven different sizes of the Mahua Ring inserted following measurement of the uterine cavity and one size of the same ring. AB - A comparative study of the performance of multi-sizes of the Mahua Ring inserted following measurement of the uterine cavity and one size of the same ring assigned at random was carried out from November 1984 to September 1985 at two hospitals in Tianjin. The experiences of 800 acceptors were analysed by life table techniques. At the end of two years, net cumulative first segment continuation rates of the multi-size and one-size Mahua device were 88.0 and 88.2, respectively. The results revealed that there was no significant difference between the groups. It is suggested that to insert one size of the Mahua Ring is as effective as the insertion of many sizes of the Mahua Ring. PMID- 2257741 TI - Effects on the endometrium, endo- and exocervix following the use of local progestogen-releasing delivery systems. AB - Some conflicting reports have appeared in the literature as to the effect of progestogens on the endometrium and on the endo- and exocervix in animals and humans. Hyperplasia of the endometrial and endocervical epithelium has been reported in some non-human primates following the administration of progestogens. In other studies no evidence has been found for such changes. In women using combined oral contraceptives, it has been claimed that the progestogen component causes adenomatous hyperplasia of the endocervix and that this hyperplastic transformation could be a precursor to adenocarcinoma of the cervix. So far, there is, however, no evidence in the literature to confirm this hypothesis. In view of the development of new delivery systems with a constant release of small amounts of progestogens, previous reports in the literature on hyperplasia and potential malignant transformation of the endometrium and the endocervix have been a matter of concern. The aim of the present study is therefore to review results from studies in animals and humans in particular with reference to the effect of a local release of various progestogens on the endometrium and the endo and exocervix. PMID- 2257742 TI - A pharmacodynamic and pharmacokinetic study of the Chinese No. 1 pill. AB - A pharmacodynamic and pharmacokinetic study of the Chinese No. 1 pill, a combined oral contraceptive containing 35 micrograms ethynyloestradiol (EE) and 600 micrograms norethisterone (NET), was performed in 29 women over a period of six months. Blood samples for analysis were taken during a pretreatment cycle, the first and 6th treatment cycles and post-treatment. Minor changes in carbohydrate metabolism occurred and these were particularly noticeable when the incremental areas under the serum concentration-time curves for both glucose and insulin in response to a glucose tolerance test were calculated. No changes occurred in the serum glycosylated haemoglobin levels. The serum concentrations of all the lipids measured (total cholesterol, triglycerides, LDL-C, HDL-C and apolipoproteins AI, AII and B) were significantly increased on treatment as were levels of Factor X, SHBG and caeruloplasmin whereas antithrombin III decreased. In 38 of the 40 treatment cycles, ovulation was suppressed. In one cycle serum oestradiol and progesterone levels showed a typical ovulatory pattern and in another there was evidence of follicular activity without ovulation. Serum EE concentrations showed a similar pattern in both treatment cycles showing that co-administration of NET did not affect EE metabolism. Serum NET levels were higher in the 6th than in the first treatment cycles. On comparing pharmacodynamic and pharmacokinetic parameters, the only statistically significant correlations were between the percentage change in triglycerides and SHBG and serum NET, but not EE concentrations, and between apolipoproteins AI and serum EE. PMID- 2257743 TI - Antifertility efficacy of the plant Striga lutea (Scrophulariacae) on rats. AB - Acacetin and luteolin, the flavones isolated from the whole plant S. lutea, have been investigated for endocrine and contraceptive properties in the pre implantation stage of pregnancy. Graded doses of these compounds, in gum acacia suspension, by oral administration from day 1 to day 4 of pregnancy showed dose dependent anti-implantation activity (5-25 mg/kg body weight/day). MED100 was found to be 25 mg/kg body weight in the day 1-4 regimen in rats for both the compounds. In another study, a single oral dose of these compounds (10 mg/kg body weight) on day 1, 2 or 3 of pregnancy prevented 100% implantation. The compounds exhibited estrogenic property at their contraceptive dose level but failed to show antiestrogenic activity. PMID- 2257744 TI - Volatile fraction of neem oil as a spermicide. AB - The volatile, odorous fraction of neem oil coded as NIM-76 obtained by steam distillation was investigated for in vitro spermicidal activity. The data showed that the minimum concentration which inhibited spermatozoal motility was 0.25 mg/ml for rat and 25 mg/ml for human spermatozoa. The effect of the drug on spermatozoal motility was found to be dose-dependent. The activity of this drug was not altered in the presence of vaginal or cervical mucus. Intra-vaginal application of NIM-76 in rabbits showed no irritation to the vaginal mucosa. PMID- 2257745 TI - Surgical education: a decade of change. PMID- 2257746 TI - The transfusion effect is influenced by the nature of MHC antigen presentation. AB - We designed a study to determine whether the mode of presentation of major histocompatibility antigens is important for the ability of donor-specific blood transfusions to prolong organ allograft survival. Donor BN rat whole blood, isolated RBC, RBC ghosts, RBC membrane fragments, or whole blood lysates were administered to Lewis rat recipients 7 days before heterotopic allotransplantation of BN hearts. Only allogeneic whole blood or RBC significantly prolonged cardiac allograft survival in this histoincompatible donor-recipient pair. Whole blood lysates or RBC ghosts and membrane fragments transfused pretransplant did not prolong cardiac allograft survival when compared with syngeneic, transfused control rats. These results suggest that the immunosuppressive effects of donor-specific pretransplant blood transfusion may depend on a three-dimensional spatial relation between cells bearing donor major histocompatibility antigens and recipient responder cells responsible for the transfusion effect. PMID- 2257747 TI - Deep hypothermic circulatory arrest induced during hemorrhagic shock in dogs: preliminary systemic and cerebral metabolism studies. PMID- 2257748 TI - Immunization-induced changes in later intra-abdominal abscess formation are mediated by cellular and humoral mechanisms. PMID- 2257749 TI - Gut-associated lymphoid tissue surface area is greater with right-sided and nonmucinous DMH-induced murine colon cancers. PMID- 2257750 TI - Release of intraluminal and circulatory peptide YY after intravenous CCK-8 in conscious dogs. PMID- 2257751 TI - The effect of endotoxin on red blood cell deformability and whole blood viscosity. PMID- 2257752 TI - The cellular response to xenotransplantation. PMID- 2257753 TI - The effects of different routes of injection on the biochemistry of adhesion site proteoglycans in metastatic v-Ki-ras-transformed 3T3 cells. AB - This study compared HSPG and CSPG in adhesion sites of isogenic metastatic lung tumor cells (v-Ki-ras-transformed 3T3 cells) after injection by different routes (IV and footpad) into athymic nude mice. The proportion of HSPG was significantly greater in experimental lung metastatic cell (IV injection) than in spontaneously metastatic cells. The proportion of CSPG in these two groups of metastatic lung cells did not differ significantly. In addition, the proportion of HSPG and CSPG in spontaneously metastatic lung tumor cells was similar, unlike experimental metastatic tumor cells. PMID- 2257754 TI - Myocardial oxygen consumption (MVO2) in regionally stunned myocardium. PMID- 2257755 TI - The effects of internal mammary artery blood flow on regional and global ventricular function. PMID- 2257756 TI - Inhibitory effect of transfer RNA on protein kinases from baker's yeast and rat skeletal muscle. AB - Sephadex G-200 gel filtration of DNA cellulose-treated crude extracts of rat skeletal muscle, revealed a broad peak-fraction of tRNA-inhibitory protein kinases (PK) coeluted endogenous substrates. In comparison, the elution profile of baker's yeast exhibited multiple peak-fractions of tRNA-inhibiting PK. Various tRNA all showed inhibition to PK. In the presence of regulatory subunit of cyclic AMP-dependent protein kinase, tRNA did not exert synergetic inhibition on PK. Moreover, the interaction of tRNA with active muscle PK fractions could not be monitored by the increment of absorbance at 340 nm. tRNA had no significant regulatory effect on the phosphorylation of actin and myosin. PMID- 2257757 TI - Histochemical characterization of esterases from three species of amphistomes. AB - Esterase activity of Gigantocotyle explanatum, Ceylonocotyle scoliocoelium and Cotylophoron cotylophorum were localized histochemically in various regions associated with nutrition, viz, integument, pharynx, sucker and gastrodermis. The intensity of the reactions varied in the different regions of the same parasite and also from species to species. The distribution and relative activity of the esterases were investigated and the results reveal that the influence of inhibitors/activators on enzyme activity varied in the different regions. Based on the inhibitory effects it is inferred that carboxylesterases are distributed in the region of the integument, pharynx and gastrodermis, acetylesterases in the suckers and cholinesterase in the subtegumental cells and muscle of these three trematodes. PMID- 2257758 TI - Evidence for transcytosis of exogenous superoxide dismutase and catalase from coronary capillaries into dog myocytes. AB - Infusion of superoxide dismutase (SOD) and catalase (CAT) into the coronary circulation protects myocardial tissue from free radical injury and improves recovery of myocardial function after a short episode of ischaemia. To investigate the ultrastructure of myocardium treated with SOD and CAT, these enzymes were injected into the left atrium of dogs prior to and during 15 min of regional myocardial ischaemia, allowing 30 min of reperfusion, and then fixing the tissue for electron microscopy. The exogenous SOD + CAT was found to promote recovery of both function and structure in these hearts. In addition, electron dense material was unexpectedly found in vesicles of capillary endothelia, between capillaries and myocyte, and in vesicles within myocytes. This occurred only in hearts treated with SOD and/or CAT, suggesting SOD and CAT was concentrated and transported across the capillary endothelium and into myocytes. The rate of transcytosis, as measured by the number of intra-endothelial vesicles, was increased in tissue subjected to ischaemia and reperfusion in the presence of SOD and CAT. These observations suggest transcytosis of SOD and CAT is an important part of the process by which these enzymes provide protection to myocardium during reperfusion after ischaemia. PMID- 2257759 TI - Prediction of the cytotoxic effects of some antineoplastic drugs on cultured T lymphoma cells by microcalorimetry. AB - The effects on T-lymphoma cells of the antineoplastic drugs Ara-C, cisplatin, vinblastine, chlorambucil and prednimustine were studied by microcalorimetry and a conventional viability assay. The heat production rate for cells was measured immediately after drug treatment and was compared with the change in cell concentration during the following generation time. The results of the microcalorimetric observations were correlated with cell death. Such correlations varied considerably for the different drugs, in particular between chlorambucil and the other drugs investigated. PMID- 2257760 TI - [General examination in current practice. Proposal for an adapted card]. PMID- 2257761 TI - [Edme Marie Miel, dentist. 1777-1830]. PMID- 2257762 TI - [Transparency of porcelain to ultraviolet rays]. PMID- 2257764 TI - [Dental care in Romania]. PMID- 2257763 TI - [Dura mater in dentistry. Focus on its use in 1990]. PMID- 2257765 TI - [103 cases of carious lesions treated with the Micro Plasma System]. PMID- 2257766 TI - [Estimation of age by a method of 2 dental criteria]. PMID- 2257767 TI - [A new concept of corono-radicular reconstruction, the Composipost (2)]. PMID- 2257768 TI - Study of morphology and deciduomal proteins of hamster endometrial cells during in vitro decidualization. AB - The objective of this study was first, to examine whether the morphological characteristics of deciduomal cells are correlate to differentiation or just to hyperplasia and hypertrophy, and second, to examine whether the deciduoma associated proteins (DAPs) are expressed consistently during decidualization in vitro and in vivo. In vitro decidualization was implemented by dissociated cell culture of Day-4-pseudopregnant endometrium. The morphology of these cultures was compared with that of undifferentiated cultures of fetal hamster fibroblast. They appeared similar morphology in the stellate shape, the binucleation and the intracellular fibers. The DAPs were identified by comparing the electrophoretic maps of one-day cultures of decidualized and nondecidualized endometrium from unilaterally scratched Day-6-pseudopregnant animals. Analysis of cytosol fraction by SDS-PAGE demonstrated the presence of four DAPs. That only one of them was growth-associated, which was concluded from its increasing expression in fetal fibroblast, and that all of them were not endometrium-specific as evidenced by their presence in other tissues. By examining their expression during in vitro decidualization, we found that timing of the DAPs' expression in vitro was not consistent with it in vivo. These results indicate that some morphological characteristics which were accustomedly used to mark deciduomal cells may relate to hyperplasia and hypertrophy instead of differentiation, and that the in vitro and the in vivo decidualization are not identical. PMID- 2257769 TI - Existence of a gonadotropin-releasing hormone-like factor in the grass shrimp (black tiger prawn, Penaeus monodon) AB - The immunological and biological gonadotropin-releasing hormone (GnRH)-like activities in the acid extract of shrimp hepatopancreas (SHE) were studied. The immunological activity determined by a GnRH radioimmunoassay was 22.3 +/- 2.7 ng per ml of SHE. SHE increased luteinizing hormone (LH) release from rat anterior pituitary glands (APs) in vitro, and its biological activity was 42.9 +/- 28.5 ng per ml. No immunological activity was found in the acid extracts of eye ball, eye stalk, nerve and heart. These results suggest that the shrimp hepatopancreas has both immunological and biological GnRH-like activity. PMID- 2257770 TI - Effects of strophanthidin on the force-frequency relationship in dog ventricular working and conducting tissues. AB - Effects of strophanthidin on force-frequency relationship were studied in dog working ventricular myocardium (VM) and Purkinje fibers (PF). In VM, both strophanthidin (0.3-1 x 10(-6) M) and driving rate increase within physiological range of 1 to 2 Hz potentiated the force of contraction. In PF, the following different responses were observed. 1. The contractile force decreased as the driving rate increased within the same range (negative staircase). 2. The positive inotropic effect of strophanthidin first increased and then declined. During the rising phase of strophanthidin inotropy, the staircase was still negative. The staircase became positive as strophanthidin inotropy declined. 3. Strophanthidin also potentiated the contractile force of extrasystolic and post extrasystolic beats as revealed by the Johnson's two-state experiments. 4. The inotropic effects of strophanthidin were mimicked by high [Ca2+] (8.1-12.1 mM) and reversed by Ca channel blockers. Effects of Ca2+ overloading are discussed and a quantitative difference in regulation of cytosolic Ca2+ between VM and PF is suggested. PMID- 2257771 TI - Retinal vessel responses to systemic autonomic stimulation in fellow eyes of patients with retinal vein occlusion. AB - The retinal vessel calibre responses to systemic autonomic stimulation were studied in fellow eyes of 11 patients with central retinal vein occlusion (CRVO) and 10 patients with branch retinal vein occlusion (BRVO), using sustained isometric muscle contraction as the stimulus. These vessel responses were compared to those of a control group of 11 subjects of similar ages. The changes in retinal vessel calibre were measured using the Quantimet Image Analyser. There was no significant difference in mean arteriolar constriction during isometric muscle contraction (mean +/- SEM) between the CRVO group (6.0 +/- 1.34%) and the BRVO group (5.4 +/- 0.31%), (p greater than 0.05), and between either of these groups compared with the control group (7.4 +/- 1.20%), (p greater than 0.50). Similarly there was no significant difference in mean venule responses between the groups (CRVO 4.9 +/- 0.48%; BRVO 4.6 +/- 0.63%; control subjects 3.8 +/- 0.90%; p greater than 0.05). The diastolic blood pressure responses were similarly not significantly different between the 3 groups (CRVO 22.3 +/- 1.27, range + 17 to 29 mmHg; BRVO 25.8 +/- 2.9 mmHg, range 18 to 45 mmHg; control subjects 21.3 +/- 1.7 mmHg, range 16 to 35 mmHg), (p greater than 0.10). The implications of the results are discussed. PMID- 2257773 TI - Trabeculectomy and extracapsular cataract extraction with posterior chamber lens implantation: a long term study. AB - Extracapsular cataract extraction with posterior chamber lens implantation and trabeculectomy was performed on 15 cataractous eyes in 15 patients: 5 were affected with chronic closed angle glaucoma and 10 with primary open angle glaucoma. This procedure offers the intraocular pressure control expected after trabeculectomy and, at the same time, gives the patients all visual benefits that cataract extraction with intraocular lens implantation warrants, without the introduction of new complications. PMID- 2257772 TI - The prevalence of autonomic neuropathy in the primary glaucomas. AB - The results of systemic autonomic nerve function studies in patients with closed angle glaucoma and ocular hypertension are reviewed. Autonomic neuropathy has been demonstrated in 58% of patients with closed-angle glaucoma and 42% of ocular hypertensive subjects, with significantly increased prevalence in ocular hypertensives with narrow iridocorneal angles. The implications are discussed, with particular reference to the pathogenesis of raised intraocular pressure. PMID- 2257774 TI - Convergent strabismus fixus in high myopic patients. AB - Patients with high myopia may develop a myopathy which frequently results in a sort of convergent strabismus fixus. Echographic and CT scan findings give evidence that a myopathic paralysis of the lateral rectus is supported by a slow pressure on this muscle squeezed between the lateral orbital wall and the enlarged eyeball. PMID- 2257775 TI - Dermolipoma: characteristic CT appearance. AB - Dermolipomas are choristomas usually located at the external canthus. Clinically they can be confused with dermoid cysts. Preoperative diagnosis of a dermolipoma is important because the surgical approach is less aggressive than for dermoid cysts. We describe the clinical aspects of ten patients with a dermolipoma and demonstrate the posterior extension of these lesions by CT. PMID- 2257776 TI - Contrast sensitivity and the diagnosis dysthyroid optic neuropathy. AB - Contrast sensitivity function (CSF) was investigated in 19 patients (34 eyes) with clinical signs and symptoms of dysthyroid optic neuropathy (DON). CSF was disturbed in 33 eyes and was shown to improve after orbital decompression. These results indicate that the CSF may be a useful supplementary test of visual function in patients with DON. PMID- 2257777 TI - A primer of ophthalmic computer graphics. AB - Computer graphics offers an unprecedented opportunity to probe new and old ideas in vision testing, without going to the expense of building dedicated equipment. However, the large variety of computer hardware is bewildering and only occasionally can commercial software tools be used. This mini review of the basic principles of computer graphics on personal computers is intended to help the newcomer to the field. PMID- 2257778 TI - [Endobronchial sonography in the diagnosis of pulmonary and mediastinal tumors]. AB - Endobronchial sonography was performed during bronchoscopy in 58 patients (48 males and 10 females; mean age 59 [29-76] years) with confirmed pulmonary or mediastinal tumour using a 6.2 or 9 F ultrasound catheter. The procedure was successfully performed in 50 patients from the trachea down to the smallest bronchi (of 2 mm diameter). Tumour tissue was not visualized in five patients with small peripheral carcinomas. In three patients the catheter probe could not be passed through the tumour region. The method provided a three-dimensional image of the bronchial wall, corresponding to the histological tissue layers of mucosa, cartilage and adventitia. Pulmonary arteries were identified by the echo free lumen and pulsatile oscillations in calibre. Tumours and lymph-nodes were echo-poor and could thus be distinguished from the echo-rich bronchial wall. Several consequences arose from these findings: laser treatment was not proceeded with in two cases, because a fairly large pulmonary artery lay near the stenosis; in three cases malignant tumours were recognized to lie either entirely intramurally or peribronchially, which had not been seen on bronchoscopy alone. It is concluded from these preliminary observations that endobronchial sonography is a highly promising addition to conventional bronchoscopy. PMID- 2257779 TI - [Obesity, body fat distribution and the incidence of breast, cervical, endometrial and ovarian carcinomas]. AB - The connection of body fat distribution (BFD) and the risk of developing mammary, cervical, endometrial or ovarian carcinoma was ascertained for 163 patients with carcinoma (mean age 49.9 [19-78] years) and 489 controls of comparable age and body-mass index. BFD was expressed as the ratio of waist and hip circumference (T/H ratio of 0.822 vs 0.781 and 0.826 vs 0.789, respectively; P less than 0.01). In premenopausal women with mammary or cervical carcinoma and in all postmenopausal women BFD was similar to that in the control subjects. A common cause of android obesity and ovarian or endometrial carcinoma may be a reduction of sex-hormone-binding globulins with an elevated serum level of free androgens and oestrogens. PMID- 2257780 TI - [Pseudoxanthoma elasticum (Gronblad-Strandberg syndrome) and rheumatoid arthritis]. AB - A 72-year-old woman, not previously known to have coronary heart disease, was admitted to hospital with an acute anterior wall myocardial infarction. The history revealed that, when about 40 years of age, a coarse skin-fold and yellowish-white xanthoma-like efflorescences had been noted around her umbilicus, the inguinal regions and axillae. These changes subsequently developed into a pathognomonic picture of pseudoxanthoma elasticum (PE), which was a significant factor in the myocardial infarction. At the age of 69 years, rheumatoid arthritis (RA), stage II after Steinbrocker, had been diagnosed on the basis of morning stiffness, symmetrical arthritis in more than three joint regions and the radiological appearance of narrowed joint spaces with erosions. Different pathological mechanisms of PE and RA change the connective tissue metabolism, thus affecting the same target tissue, but there is no known connection between the two diseases. PMID- 2257781 TI - [Cholesterol embolism of the kidney]. PMID- 2257782 TI - [The importance of protein growth factors for the local regulation of bone growth]. PMID- 2257784 TI - [The preservation of ultrasonic documentation images]. PMID- 2257783 TI - [The 1990 Nobel Prize for Medicine]. PMID- 2257785 TI - [Is microwave-heated milk harmful?]. PMID- 2257786 TI - [The use of fibrin adhesive in upper gastrointestinal hemorrhage]. PMID- 2257787 TI - Causes of failure of neonatal patient triggered ventilation. AB - Causes of failure of patient triggered ventilation (PTV) in neonates have been determined. In particular we have investigated the importance of the timing of ventilator inflation in the spontaneous respiratory cycle and hence the respiratory interaction provoked during PTV. Fifty-six infants (median gestational age 29 weeks) were studied on 63 occasions using two different trigger systems, changes in airway pressure and airflow. After one hour of PTV, only 26 infants were synchronous (inflation coinciding with and occurring only in inspiration), 8 were apnoeic. In the remaining 29 infants, inflation extended into expiration, five of whom were actively expiring. The timing of inflation in the spontaneous respiratory cycle and the interaction provoked was significantly related to the trigger delay, but not the inflation time or type of trigger used. Oxygenation after one hour of PTV improved in infants in whom inflation occurred in inspiration only and in some when it extended beyond. Failure of long term PTV was more common, however, in infants in whom inflation extended beyond inspiration (i.e. asynchronous), but this did not relate to the type of trigger used. Failure was also associated with a long trigger delay (P less than 0.01), a very short inflation time (P less than 0.01) and commencement of PTV early in the infant's illness (P less than 0.05). We conclude that synchrony is the most beneficial respiratory interaction during PTV. Our data suggest that this interaction would be more consistently provoked by the use of a sensitive triggering system which ensured a short trigger delay. PMID- 2257788 TI - Effects of behavioural states on cardiac output in the healthy human fetus at 36 38 weeks of gestation. AB - Doppler velocity waveforms from atrioventricular valves were recorded in 20 healthy fetuses at 36--38 weeks of gestation during both behavioural states 1F (quiet sleep) and 2F (active sleep). No significant changes were found in the ratios between the velocities during early passive ventricular filling and active ventricular filling (E/A ratios) at the level of both mitral and tricuspid valves when the measurements obtained during states 1F and 2F were compared. Moreover, during state 2F the left ventricular output increased and the right ventricular output decreased, resulting in a marked modification of the right to left cardiac output ratio. Our data suggest a redistribution of cardiac output in favour of the left side of the heart during state 2F. PMID- 2257789 TI - Neonatal intracranial hemorrhage: I. Changing pattern in inborn low-birth-weight infants. AB - Many reports of the occurrence of periventricular-intraventricular hemorrhage (PVH-IVH) are biased by the inclusion of both inborn and outborn infants. To obviate this selection bias we examined a large inborn population of low-birth weight infants to determine if the incidence of PVH-IVH changed over a 3-year interval from March, 1982 through February, 1985. Serial cranial ultrasonography was performed in 463 consecutive infants of birth weight less than or equal to 1500 g who survived for more than 8 h. The incidence of PVH-IVH decreased from 31.5% and 29.3% in years 1 and 2, respectively, to 23.7% in year 3 (P less than 0.05). The latter reflected a fall in the incidence of grades III and IV PVH-IVH, but no change in the incidence of grades I and II. This observation was not attributable to changes in mortality, the distribution of infants by birth weight and estimated gestational age in each year of the study, or infants excluded from the analysis. Contrary to most reports, 21.9% of all PVH-IVH during the 3 years were first diagnosed after 14 days postnatal age and were predominantly grade I. These results document not only a change in the epidemiology of PVH-IVH in an inborn population, but also the importance of serial cranial ultrasonography beyond the first week of life. PMID- 2257790 TI - Circadian rhythms in preterm infants: a preliminary study. AB - A method has been developed for long-term continuous recordings of several physiological variables in humans, including body movements, core temperature, heart rate and respiratory rate. This method enabled us to study circadian rhythms of body temperature and rest-activity in preterm infants. In 5 out of 9 infants (recorded at 28-34 weeks conceptional age) circadian rhythms were found in body temperature. We conclude that circadian rhythmicity is present during the early neonatal period in certain physiological variables (body temperature) but not in others (rest-activity). PMID- 2257791 TI - Coincidence of behavioural state parameters in the human fetus at three gestational ages. AB - The fetal behavioural state concept was used to study fetal rest-activity cycles in normal pregnancies at gestational ages of 32 and 38 weeks. In addition, it was investigated if clustering of fetal movements was already present in recordings obtained at 20 weeks. At 20 weeks, 17 periods lasting longer than 3 min were found in which fetal body movements were absent. The mean duration of these periods was 4.0 +/- 0.8 min. On the basis of random scattering of movements on a time axis, it appeared unlikely that these periods of inactivity occurred by chance alone. At 32 and 38 weeks, data on body movements were combined with data on eye movements and the FHR pattern. At 32 weeks, true fetal behavioural states were not found. The average coincidence of 1F to 4F was 58%, while only 23% was to be expected if state parameters had fulfilled state criteria purely by chance. At 38 weeks, coincidence of 1F to 4F had increased to 80% (P less than 0.001). Expected coincidence purely by chance was 30%. True fetal behavioural states were found in 17 out of 35 recordings. For transitions from 1F into 2F, the FHR changed relatively early, i.e. as first or second parameter, while for the reverse transitions it changed relatively late (P less than 0.05). There was no clearly preferred sequence for body and eye movements within transitions. PMID- 2257792 TI - Visual evoked potentials in term light-for-gestational-age infants and infants of diabetic mothers. AB - The latency and amplitude of the first negative peak of visual evoked potentials (VEP) were evaluated in 52 term infants, investigated within 48 h after birth. Sixteen were light-for-gestational-age (LGA), 16 were appropriate-for-gestational age (AGA) and 20 were infants of diabetic mothers (IDM). The VEP latency was shorter in LGA infants compared to AGA infants, and it was closely related to the birth weight deviation. The VEP latency was inversely related to gestational age and positively related to head circumference. When corrected for gestational age and head circumference, the VEP latency was not significantly different between the subgroups, nor related to the birth weight deviation, ponderal index or skinfold thickness. Thus, it could be argued that the high conduction velocity in LGA infants is due to stress maturation or alternatively due to the smaller head circumference. The VEP amplitude was higher in LGA infants when compared with AGA infants, and inversely related to the birth weight deviation. No differences were found in VEP latency or VEP amplitude between IDM and AGA infants. PMID- 2257793 TI - [Basic considerations on the use of the Excimer laser in dentistry]. AB - SEM studies showed that irradiation in the energy density range of 4-6 J/cm2 resulted in the removal of hard tooth structure without causing thermal alterations of the tissues. In this process (photoablation) the natural structures of the tissues are "exposed". The surface structure thus produced in dentin depends on whether the dentin tubules are hit transversally or longitudinally and varies accordingly. The surface structure of enamel, as well, is determined by the alignment of the prisms. When the laser beam was optimally adjusted (energy densities of 4-6 J/cm2 and peripheral fading), no structural changes could be demonstrated in the depth of the tissue. PMID- 2257794 TI - [Mercury release of silver amalgam fillings in vitro]. AB - In vitro mercury release from silver amalgam fillings was analyzed by ICP (Inductively-coupled-plasma-atomic-emission-spectroscopy). Within 14 days 63.2 micrograms Hg and 41.5 micrograms Hg respectively, were released from unfinished and finished amalgam fillings (n = 5). The amounts of mercury found in this study were several times higher compared with the results from other in vitro-studies. PMID- 2257795 TI - [Sensory and inflammatory reaction mechanisms in the dental pulp]. AB - Laser-Doppler-flowmetry is used to show whether electrical stimulation of the rats tooth pulp leads to reactions such as neurogenic inflammations. Following electrical stimulation, a flow reduction with a subsequent flow increase can be observed After experimental elimination it can be shown that both sympathetic and nociceptive fibres are involved in this reaction. Thus the neurogenic inflammation of the dental pulp is a mechanism allowing early and localised reactions to noxious stimuli. PMID- 2257796 TI - [The efficacy of paracetamol (Tylenol) and acetyl salicylic acid (Aspirin) in treating postoperative pain]. AB - In a randomized, double-center, double-blind, parallel group study the analgesic effect of a single dose of paracetamol (1000 mg) and acetyl salicylic acid (1000 mg) was compared with placebo in patients with moderate to severe postoperative pain following the surgical removal of a wisdom tooth. The most important finding was the statistically significantly shorter period until the onset of the action of paracetamol as against acetyl salicylic acid. PMID- 2257797 TI - [Morphological and functional characteristics of the palatal mucosa and the palatine glands]. AB - Histologic findings of the palatal mucosa and the palatal glands of 73 patients with and without upper dentures were compared with distinctive marks, complaints and clinical diagnoses as well as with the secretion of the minor salivary glands. Patients complaining of oral burns show the same rate of patho-histologic findings as those without any complaints. Inflammation and atrophic reactions of the palatal mucosa and the palatal glands do not reduce the secretion rate of the minor glands. In these cases, however, considerable changes of the quotient exist between sodium and potassium ions of the palatal saliva secretion. Signs of inflammation of the palatal tissues were seen more frequently in full denture wearers and especially in those wearing upper dentures during day and night. Causative factors of denture incompatibility are discussed. PMID- 2257799 TI - [Transcutaneous electric nerve stimulation (TENS) in chronic neuralgiform facial pain]. AB - Transcutaneous nerve stimulation has a positive effect an patient's pain. Even in so-called "hopeless cases" an improvement in at least one of the investigated criteria i.e. intensity of pain, duration of pain and consumption of analgetics could be achieved by TENS. PMID- 2257798 TI - Extension of the jaw opening reflex and effects of a central muscle relaxant (afloqualone) in the rat. AB - How widely the jaw opening reflex (JOR) extends was examined in the rat. Recording was done in the anterior (AD) and posterior (PD) digastric, sternohyoid (SH) and sternomastoid (SCM) muscles. Electric stimulation was given to the mandibular incisor pulp. Evoked electromyogram (EMG) activities could be recorded in each muscle. The thresholds for JOR increased from AD to SCM. Intravenously administered afloqualone, a centrally acting muscle relaxant, inhibited both JOR and its parallels promptly and dose-dependently. The possible clinical significance in temporomandibular joint dysfunction will be discussed. PMID- 2257800 TI - [Double blind biometric study on postoperative effects of analgesics]. AB - A double blind trial to study the effects of analgetics was carried out in patients suffering from pain after third molar osteotomy. 204 patients were evaluated after random allocation to treatment with paracetamol 500 mg and paracetamol 500 mg plus codeine 30 mg. Statistical evaluation revealed a tendency for better analgesia using the combination of paracetamol and codeine. For further studies an exact stratification for sex and age is necessary. Sample sizes of 150 patients are necessary for each parameter. PMID- 2257801 TI - [Postoperative analgesics consumption]. AB - Prescription habits, dose and form of application of analgesics were investigated in a retrospective study of postoperative pain alleviation involving 250 patients. On the basis of clinical and pharmacological criteria, a prescription regime is presented for Paracetamol as used singly and in combination with Codeine. The prescription regime has been tested in a prospective study involving 50 patients and found to be effective. PMID- 2257802 TI - [Treatment of neuralgiform maxillofacial pain with hydantoin (Phenhydan)]. AB - Within 4 years a total of 49 patients have been treated for neuralgiform symptoms. 19 patients were symptom-free after 4 to 5 days of monotherapy. Including additional carbamacepine in the treatment of the remaining 30 patients produced successful results in 12 cases. Eight out of the remaining 18 patients showed satisfactory results after psychoactive drugs had been added. It was only in 10 cases that the symptoms could not be eliminated. PMID- 2257803 TI - [Pain as an indication for functional TMJ surgery]. AB - In 113 patients presenting with painful impediment of jaw function, which did not respond to non-surgical treatment, several kinds of functional surgery of the temporomandibular joint were applied. Comparison of the pre- and postoperative pain profiles of these patients show that good results from the surgery methods used could generally be expected when the patient, preoperatively, had pain restricted to the TMJ area with function. More unfavorable results were shown in patients with pain already present for years, muscular or bilateral pain as well as pain not related to function or pain at night. Continuous pain should only be seen as an indication for surgery with rheumatoid arthritis of the TMJ. PMID- 2257804 TI - [Treatment of implant-induced pain conditions in the maxillofacial area]. AB - The implantation of dental implants may lead to severe pain syndromes (not reckoning postoperative pain and discomfort). Pain in the upper jaw is usually caused by inflammations like sinusitis, often in combination with an oroantral communication, rhinitis and osteitis, whereas pain in the lower jaw is often caused by injuries of sensitive branches of the mandibular nerve, mostly the inferior alveolar nerve. In these cases the therapy of pain should be causal, which means removal of the implant and treatment of the pathologic consequences of implantation. Especially the possibilities of micronerval surgery are emphasized within this article. PMID- 2257805 TI - [Therapy of masticatory dysfunction]. AB - A representative sample of patients who had presented with masticatory dysfunction at our clinic was assessed immediately as well as after longer periods following therapy. The results of this epidemiologic study indicate that those cases in which isolated stressors constituted the main etiologic factor are most responsive to therapy, but also most likely to recur. When occlusal interferences are involved, therapeutic success will depend heavily on the degree of destruction of the different articular structures. Patients presenting with psychic disorders causing somatic disturbances in the orofacial region or with primary TMJ affections such as polyarthritis or polyarthrosis are the most resistant to therapy. PMID- 2257806 TI - [The biomechanics of space closure and its dependence on the periodontal attachment]. AB - The biomechanics of space closure in adult patients with loss of periodontal attachment is described. In order to achieve an even force distribution in the periodontium, force was reduced and the moment to force relationship was increased. beta-TMA-T Loops of 0.016 inch x 0.022 inch and 0.017 inch x 0.025 inch cross sections were investigated. With an automatic testing device force and moment values were determined. PMID- 2257807 TI - [Post-treatment evaluation of the periodontal situation of unerupted and ectopic teeth after orthodontic movement]. AB - The post-treatment evaluation of 83 patients demonstrated that orthodontic mobilization of unerupted or ectopic teeth is successful both, under periodontal and functional aspects. The results did not show any dependence on the age of the patients. Thus, the indication for orthodontic mobilization may be interpreted more broadly. PMID- 2257808 TI - [Changes in periodontal parameters during orthodontic treatment]. AB - Five different parameters, i.e. proximal plaque index, sulcus bleeding index, clinical crown height, width of keratinized gingiva and probing depth, were examined in 70 treated patients before, during and after orthodontic treatment. A total of 30,000 individual data were collected. All patients were examined at three different appointments. Differentiations were also made between male and female patients and between patients treated with fixed and removable appliances. Radiographs were taken in a part of the patients before and after treatment for assessment of the interdental septa and root integrity. PMID- 2257809 TI - [Effects of orthodontic expansion of the mandibular arch on the periodontal condition of the posterior teeth]. AB - In the present study we examined the long term influence of orthodontic mandibular arch expansion therapy on the periodontal condition of the posterior teeth. 11 years after the end of treatment 31 former patients of our clinic were compared with a control group of matched age and sex distribution. Although we found some additional loss of periodontal attachment for the treated group this differences were not considered to be of clinical significance. Within the treated group the stability of the orthodontic treatment result seemed to be correlated with more favourable periodontal conditions. PMID- 2257810 TI - [The effects of orthodontic treatment on periodontal findings in adults]. AB - After periodontal therapy 12 patients with advanced alveolar bone loss were orthodontically treated and recalled for approximately 51.1 months. Orthodontic tooth movement resulted in a mean overjet reduction of 1.7 mm, a mean overbite reduction of 1.3 mm and closure of the anterior spaces. No significant differences were observed in the probing depths and attachment levels between the test and control teeth. 31% of the treated teeth showed signs of root resorption. The results indicate that orthodontic therapy in patients with successfully treated advanced periodontal disease does not lead to further attachment loss if the patients are periodontally well maintained. PMID- 2257811 TI - [Anatomy and physiology of the periodontium in adults under the conditions of orthodontic tooth movement]. AB - During orthodontic tooth movement, the periodontal ligament (PDL) transduces the applied forces to the surrounding bone and is involved in the induced remodelling of periodontal fibres and alveolar bone. Due to its delicate localization between two hard tissues, the PDL is, however, prone to traumatic injuries resulting from excessive forces. With regard to the necessary remodelling processes, the adult PDL is illprepared, as all relevant physiologic cell activities, such as rate of mitosis or fibre and bone turnover, are considerably slower and have to be activated first. Furthermore, these cell activities apparently cannot be stimulated to the same level as in juvenile tissues. Thus, tooth movement, particularly in the beginning of treatment, is inevitably slower in adults than in young individuals. Any attempt to accelerate movement by applying heavier forces bears the risk of possible traumatic injuries to periodontal and root tissues. PMID- 2257812 TI - [Biomechanical principles of orthodontic movement of teeth with periodontal involvement]. AB - The presence of a reduced periodontal attachment has three fundamental effects on orthodontic tooth movement: the diminished resorptive bone surface necessitates a reduction in the magnitude of force applied; the apical shift of the center of resistance requires an adaptation of the force systems used; (moment/force ratio); the limited anchorage quality of periodontally susceptible teeth has to be considered biomechanically. Orthodontic movement of teeth with reduced attachment therefore requires differented planning and application of force systems in order to avoid root resorption and further bone loss. PMID- 2257813 TI - [White sponge nevus]. AB - White sponge nevus is a rare disturbance of the keratinization of the oral mucosa. Differential diagnosis and therapy are discussed on the basis of one case with typical clinical and histologic findings. PMID- 2257814 TI - [The adaptive responses of human oral microorganisms to sorbitol]. AB - It was the goal of this study to evaluate the extent to which sorbitol is metabolized by the oral microflora of persons adapted to this sugar substitute (diabetics). Resting saliva of 25 test persons with juvenile diabetes mellitus was incubated with sorbitol or sucrose in the Warburg-system both under aerobic and under anaerobic conditions. Saliva of 25 healthy persons served as control. Sorbitol was metabolized faster and to a higher total amount in the diabetic group. These results indicate that if sorbitol is offered continuously, the oral microflora will adapt and will metabolize sorbitol to a considerably higher extent. PMID- 2257815 TI - [Development and significance of the cuticula dentis for the epithelial attachment]. AB - The purpose of this study was to identify those conditions governing presence and function of the secondary cuticle (cuticula dentis) by means of a clinical evaluation (Periodontal Status, Plaque Index, Decayed-Missing-Filled-Index) as well as radiological, bacteriological (plaque swabs) and histological studies. The secondary cuticle could be demonstrated mainly in individuals with mild bone resorption and minimal loss of periodontal attachment (age 20-50 years). In most cases there was an intimate attachment of the junctional epithelium to the enamel or cementum surface. However, in most elderly subjects (older than 50 years) the secondary cuticle was found only in fragments or was not detectable at all. In these cases the junctional epithelium had proliferated apically (towards the apex dentis) and was only punctiformly attached to the tooth surface. Our histological findings suggested that the secondary cuticle is a secretory product of the junctional epithelium. Therefore, we assume it to be the essential structure in maintaining epithelial attachment. PMID- 2257816 TI - [Limits of orthodontic treatment of periodontally affected dentitions]. AB - Basically there are no exact metric limits in terms of probing depth or loss of periodontal attachment, up to which orthodontic tooth movement is possible. Each individual treatment plan depends on a great variety of factors and is limited particularly by biomechanical considerations (uncontrolled force systems, limited anchorage quality) and the risks associated with specific periodontal conditions (tooth/alveolar bone topography, sinus recessus, activity and prognosis of periodontitis). PMID- 2257817 TI - The significance of the width and thickness of the gingiva in orthodontic treatment. AB - The results of the studies reviewed have shown that, while the apico-coronal width of the gingiva is unlikely to affect the development of a recession defect, the thickness of the marginal soft tissue may be essential for the prevention of soft tissue recession in conjunction with orthodontic therapy. The clinical implication of these findings is that tooth movement--particularly tooth movement in facial/lingual direction--should be preceded by careful examination of the dimensions of the tissues covering the "pressure side" of the teeth to be moved. As long as the tooth can be moved within the envelope of the alveolar process, the risk for harmful side-effects in the marginal soft tissue is minimal, irrespective of dimensions or quality of the soft tissue. If, however, the tooth movement is expected to result in the establishment of an alveolar bone dehiscence, the volume (thickness) of the covering soft tissue must be considered as a factor which may influence the development of soft tissue recessions during, as well as after, the phase of active orthodontic therapy. A thin gingiva may serve as a locus minorus resistentiae to developing soft tissue defects in the presence of bacterial plaque. This means that in tooth regions with a thin covering soft tissue, the patient must be encouraged to carry out effective but at the same time non-traumatic plaque control measures. If surgical intervention is considered in order to reduce the risk for development of soft tissue recession following orthodontic therapy, this should aim at increasing the thickness of the covering tissue (e.g. by the use of connective tissue grafts) and not the apico-coronal width of gingiva. PMID- 2257819 TI - [Interproximal tooth cleansing of abutment teeth and pontic design]. AB - This clinical study was an attempt to find out if a patient's home care plaque control at his or her abutment tooth is more effectively enhanced by a modified ridge lap or a hygienic pontic design. Oral hygiene was performed either with a tooth brush alone or in combination with an interdental brush. We found that the effectivity of interproximal toothcleaning was not influenced by the pontic design and that only interdental brushes permit a good plaque control at the proximal area of the abutment tooth. This implies that "self cleansing" is non existent in these tooth areas. PMID- 2257818 TI - [Effects of amalgam fillings on the mercury concentrations in amniotic fluid and breast milk]. AB - Human amniotic fluid was gained from 95 pregnant women by amniocentesis (group 1) and from 20 women during delivery (group 2). The concentrations of inorganic mercury in amniotic fluid as assessed directly by cold-vapor atomic absorption spectrophotometry (CV-AAS) averaged 0.29 +/- 0.1 microgram/l in group 1 and 0.86 +/- 0.25 microgram/l in group 2. Surface areas of dental amalgam fillings were also estimated in these women and ranged between 0 and 930 mm2. There was no correlation between the surface area of maternal amalgam fillings and the concentrations of inorganic mercury in amniotic fluid (r = -0.122 and -0.069, respectively). Furthermore, no positive correlation existed between amalgam fillings and the concentration of total mercury in maternal blood (4.48 +/- 2.33 micrograms/l) and in neonatal blood (3.28 +/- 1.57 micrograms/l) as measured by CV-AAS in group 2 (r = -0.4 and -0.12, respectively). Concentrations of total mercury were also measured by CV-AAS in the breast milk of 86 women, five to ten days after delivery. These concentrations averaged 1.9 +/- 1.6 micrograms/l and were also not significantly correlated to the maternal amalgam surface areas (r = 0.188). In conclusion, maternal amalgam fillings are of no importance for the mercury load of the fetus and the neonate. PMID- 2257821 TI - [Studies on the evaluation of electronic functional recordings]. PMID- 2257820 TI - [Investigation of plastic materials for temporary crowns and bridges]. AB - Chemical structure, mechanical and physical properties, and biocompatibility of six plastic materials for temporaries were examined. Their clinical usefulness in relation to application and methods was compared. PMID- 2257822 TI - [Continuous case control using a subsequent computer-supported documentation system]. AB - A computer system for recording clinically relevant parameters is described. The system represents a modification of previous methods for the collection and evaluation of follow-up data. Once installed, it permits the observation of dental therapy and subsequent treatment measures without additional organizational requirements. The results show the number of cases that can be controlled over 5 years without special appointments for reexamination. PMID- 2257823 TI - [Bodily movement of teeth in atrophic jaw segments]. AB - This experimental animal study was conducted to evaluate the extent of bone restructuring after bodily movement of teeth into an area of atrophied alveolar bone. The measured values as well as the radiographic and histologic data indicate that partial or total bone restructuring occurs depending on the rate of tooth movement. In our experiment we observed marked bone formation at an average tooth movement rate of 15 microns/day, whereas no noteworthy bone formation occurred at higher rates of tooth movement (26-40 microns/day). Basically, an improvement in attachment is possible with bodily movement in atrophic alveolar bone. However, it is important to remember the delayed periosteal reaction when planning the mechanics to be applied. PMID- 2257825 TI - [Rates of root resorption in orthodontically moved, periodontally affected and healthy teeth]. AB - The aim of this SEM-study was to obtain a quantitative analysis for comparing the extent of root resorption in orthodontically treated teeth, in teeth with reduced periodontium and in healthy teeth. By using a statistically valid method the highest amount of root resorption was established in orthodontically moved teeth. The teeth with loss of attachment showed a significantly higher amount of root resorption than healthy teeth. This finding complicates orthodontic treatment in teeth with reduced periodontal attachment. PMID- 2257824 TI - [Intrusion of periodontally affected teeth using a polyglactin-910-membrane (Vicryl)]. AB - The present study was to determine, if the use of a Vicryl membrane following a full flap procedure and combined with subsequent orthodontic intrusion renders the formation of new attachment more predictable. In an animal experiment eight premolars with reduced periodontia were intruded. The findings were analyzed histologically, histometrically and radiologically. The results provided the basis for a new general classification of the formation of new cementum and bone substance. This classification may serve as a reference system for future studies. The combined orthodontic/periodontologic approach resulted in complete repair and functional restructuring of the destructed interradicular bone and may be a promising alternative in the treatment of furcation invasion. The proximal root surfaces showed less increase in attachment or even further bone loss. Histometric comparison revealed no significant differences between interradicular and proximal root surfaces. PMID- 2257826 TI - [Fundamental biologic considerations in endodontics]. AB - Over the years a substantial body of scientific data has accumulated suggesting that most pulpal and periapical disease processes are induced and maintained by bacterial organisms. On the basis of this knowledge, this review paper discusses rationales and essential steps in endodontic therapy. It is concluded that the focus in pulpectomy procedures (vital pulp therapy) is on preventing bacteria from establishing themselves in the root canal. In cases of infected pulp necrosis, treatment is geared towards the complete elimination of pathogenic organisms that are already present in the root canal system. In both instances, vital or necrotic pulp, it is important that such conditions be established to avoid recurrence of infection following treatment. PMID- 2257827 TI - [Spectroscopically controlled preparation of hard tooth structures using a UV laser]. AB - During preparation of hard tooth structures with a 193nm-(ArF)*-excimer laser, the laser beam produces a specific fluorescent light whose spectrum is governed by the structure of the specimen. These fluorescence spectra allow an analysis of the removed tissues. The data thus obtained may be used to control the laser system so that only specific structures, such as carious tissue, are removed: reproducible fluorescence spectra were established by means of standardized samples (pure synthetic hydroxyl apatite ceramics, enamel, dentine and carious dentine) and the characteristic absorption bands (peaks) for the different substances were measured. With the aid of electronic data processing these reference spectra could be compared with the fluorescence spectra obtained during preparation. When a spectrum differed from the predefined limits of relative intensities, preparation was stopped. Since ablation per pulse is only to a small depth (0.04-4 microns) with the 193nm-(ArF)*-eximer laser, this feedback system of ablation and fluorescence spectroscopy allows decisions as to continuing or stopping the preparation process to be taken within the range of a few microns. PMID- 2257828 TI - [Comparative biological testing of Ketac-Bond glass ionomer cement]. AB - The biocompatibility of a fast setting glass-ionomer cement and of reference materials (zink-phosphate cement, silicate cement, ZOE, composite) was assessed in a comparative biological study. Cytotoxicity testing revealed 90% counted cell numbers after incubation for 96 hours. Subcutaneous implantation tests resulted in slight, moderate and severe connective tissue reactions. In contrast to these results the three different usage tests revealed slight, reversible pulp reactions in rat incisors, pig and human teeth. After 90 days of testing there was no chronic persistent pulp irritation. It may be concluded that Ketac-Bond, is an acceptable restorative material. PMID- 2257829 TI - [Quantifying bacteriological findings in the subgingival flora]. AB - The variation of selected bacteriological parameters was investigated in 25 untreated A. actinomycetemcomitans-associated periodontitis patients. Samples of subgingival plaque were collected twice within 6 weeks with paper points for cultivation as well as with curettes for analyses of the morphological composition. Total counts of colony forming units, counts of A. actinomycetemcomitans as well as proportions of spirochetes were determined. Our results suggest a high reproducibility of quantitative data if a standardised sampling procedure with paper points is employed. On the other hand, considerable differences were observed in the morphological composition of subgingival plaque. PMID- 2257830 TI - [The effects of local anesthesia on the thermoregulation of the tooth pulp]. AB - Laser Doppler flowmetry was used to measure the effects of local anesthesia on the thermoregulation of the tooth pulp. Heat affecting the pulp is physiologically offset by a reactive increase in blood flow. An increase in temperature from 35 degrees C to 45 degrees C results in an increase in blood flow by 100%, on an average. Local anesthetics produce a reversible block of this protective mechanism, thus eliminating more or less the reactive increase in blood flow. Under local anesthesia the defence power of the tooth pulp against noxious temperatures seems to be considerably reduced. PMID- 2257831 TI - [New electric techniques for root canal length measurement]. AB - Reliable measurements of electrical resistance have recently been shown to be inaccurate for root canal length determination. By contrast, measuring differences in impedance allows impedance gradients to be recorded unaffected by electrode phenomena. Although technical problems concerning the application of the impedance gradient method have not yet been solved, mathematical, experimental and clinical findings show that root canal lengths can be reliably determined by this electrophysical method. PMID- 2257832 TI - [Drying of root canals]. AB - The dryness of root canals was checked using special paper points prepared with an indicator medium. In the presence of moisture these paper points promptly change from white to blue in color. In a two-step in vitro experiment, moisture was always demonstrated at the apical stop and in the apical third of the canal wall, although according to clinical criteria we believed the root canal to be dry. The results were not influenced by any previous manipulations of the prepared root canals. It may be recommended for routine root canal therapy to observe the following rules: 1. use alcohol for the last irrigation, 2. keep using larger paper points in between, 3. use 2 to 3 paper points more after you believe the root canal is dry, 4. remove the last paper point right before obturating the root canal. PMID- 2257833 TI - [Removal of fractured root canal instruments using the Canal Finder System]. AB - Retrieval of fractured instruments from the root canal by means of the Canal Finder-System was studied in 22 extracted teeth and in 26 clinical cases. In vitro the fragment could be removed in 6 cases and bypassed in 6 cases. In 10 cases the use of the automated device remained without success. In vivo 8 of 26 fragments were removed completely, 4 fragments were bypassed, and in 14 teeth the fragment could neither be removed nor bypassed. In 7 cases the root canal was perforated, in one tooth the fragment was pushed through the apical foramen. The Canal-Finder-System may be used as an auxilliary device for the retrieval of fractured instruments. PMID- 2257834 TI - [Mercury concentrations in placing of amalgam fillings]. AB - In a laboratory experiment a Mercury Vapor Analyzer was used to measure the mercury vapor concentration for 15 minutes during the filling of artificial cavities with amalgam. It was the object of this experiment to determine the effects of suctor type and condensation technique on the mercury concentration profile. When both suctors were used in the experimental "oral cavity" (420 m3), the mercury concentration was below 0.01 mg (Hg/m3. There was no statistically significant difference between mechanical and manual condensation. PMID- 2257835 TI - [SR Isosit composite inlays in a short term clinical test]. AB - This in vivo study assessed the clinical behaviour and early cavomarginal breakdown of a total of 42 "SR-Isosit" composite inlay restorations. Indirect examination of replica models by means of stereomicroscope and SEM-analysis indicated a stepwise loss of marginal adaptation within the six month period of clinical use. Microfractures were most frequently found in inlay margins located on functional cusp sites, while the resin luting agent still remained in place on etched enamel. PMID- 2257836 TI - [Thermal effects in the dental pulp caused by laser radiation from various laser types]. AB - In this in vitro study the temperature rises occurring in the dental pulp during laser irradiation were measured. Infrared laser radiation (CO2 and Nd: YAG) had great thermal effects on the pulp tissues. At an average power output level of 5 W temperature rises of approx. 40 degrees C within 100 s were observed. The effect of a cooling system was negligible. Radiation from an ArF excimer laser (193 nm) at an average output of 5 W caused only slight thermal changes, when an airstream was used to remove the fragments of photoablative decomposition of the dental tissues. The temperature in the pulp chamber increased by approx. 5 degrees C after 6 min. This result leads to the conclusion that only ArF excimer lasers may be effectively used in the mouth without producing inacceptable thermal effects in the dental pulp. PMID- 2257838 TI - Capillary electrophoresis. PMID- 2257837 TI - Capillary electrophoresis: present state of art. PMID- 2257839 TI - Zone broadening in electrophoresis with special reference to high-performance electrophoresis in capillaries: an interplay between theory and practice. AB - Approximate equations have been derived for the total (final) zone width (plate height, plate number and resolution) as a function of the width of the starting zone and of the zone broadening caused by diffusion. Joule heat, adsorption and the difference in conductivity (delta kappa) between a solute zone and the surrounding buffer. Two cases are treated: (A) the conductivity differences eliminate entirely or (B) partially, the diffusional broadening at one boundary of a zone. When adsorption is negligible one can derive from these equations the field strength - and for case A also the electrical conductivity - that gives the minimum zone broadening (plate height). Interestingly, at this minimum, contributions to the zone broadening from diffusion. Joule heat and conductivity differences have the ratio 4:1:1 in case A. In case B the ratio between the broadening caused by diffusion (including that caused by conductivity and pH differences) and broadening due to Joule heat is 4:1. The total zone width, plate height and optimal field strength calculated from the derived equations agree satisfactorily with experimental values. A simple method to estimate the variance of the zone broadening caused by the Joule heat led to a formula similar to that calculated mathematically. An appropriate width of the starting zone can be calculated rapidly by means of a simple formula. Following a run the true width can be estimated graphically from measurements of plate heights or zone widths at low field strengths. For high resolution the width of the starting zone usually should not exceed 0.5 mm. A new principle for the design of multi-buffer systems which generate sufficiently narrow starting zones has been developed for carrier free zone electrophoresis. This zone sharpening method permits application of wide zones of concentrations below the detection limit of the monitor. The diffusion coefficient (D) and the universal parameter D/mu (mu = mobility) appear in many of the equations derived and are often the only variables which are not easily accessible. Simple methods have therefore been developed by which they can be determined with sufficient accuracy. Fortunately, they are raised to the power of 1/5 in many formulas and therefore only a rough estimation is required. True plate numbers (calculated in the absence of electroendosmosis) often differ considerably from apparent plate numbers (calculated in the presence of electroendosmosis). A mathematical relationship between the true and apparent plate numbers has been derived.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2257840 TI - Application of micellar electrokinetic chromatography to pharmaceutical analysis. AB - Electrokinetic chromatography is a new type of analytical separation method which belongs to the group of high performance capillary electrophoretic techniques but whose separation principle is based on that of chromatography. The solute distributes itself between a carrier and the surrounding medium. The carrier, which corresponds to the stationary phase in conventional chromatography, can be transported by electrophoresis with a different velocity from the surrounding medium. The separation is achieved by the differential solute distribution and the differential migration of the carrier. The charged molecules or charged molecular aggregates are employed as the carrier. Various kinds of carriers are available for electrokinetic chromatography along with different partition mechanisms. Among them, micellar electrokinetic chromatography, which employs an ionic micelle as a carrier, has become the most popular method because of its unique and attractive characteristics as well as the separating capability of electrically neutral or nonionic solutes in comparison with capillary zone electrophoresis. The present paper describes the principle, separation characteristics and its application to the analysis of pharmaceuticals. PMID- 2257841 TI - Calibration of polyacrylamide gel columns for the separation of oligonucleotides by capillary electrophoresis. AB - Polyacrylamide-filled gel columns are used to separate oligonucleotide samples. For homopolymeric standard samples, plots of migration time versus molecular size are presented over a range of 30-160 bases. With 2.5-4% T and 3.3% C gels, good resolution over the examined mass range, with peak width at half height of 3 to 6 s, is obtained by applying electrical fields of 200-400 V/cm. The separation of heteropolymeric nucleotides by slab gel electrophoresis under routine conditions was compared with capillary gel electrophoresis. Using the same column and the same separation conditions, the plot of migration time versus base number is linear with an identical slope for three oligonucleotide samples which were examined, allowing a calibration of a gel-filled capillary for molecular mass determination. PMID- 2257842 TI - Capillary isotachophoresis with UV and tandem mass spectrometric detection for peptides and proteins. AB - The application of capillary isotachophoresis (CITP) and combined CITP-mass spectrometry (MS) for peptides and proteins is demonstrated. Separation of simple peptide mixtures, as well as enzymatic digets of proteins, is also reported using CITP with UV detection. The potential utility of CITP for proteins is demonstrated. Initial studies of combined CITP-MS of enzymatic digests is also demonstrated, showing the potential for rapid sequence determination. PMID- 2257843 TI - Experimental and theoretical dynamics of isoelectric focusing: IV. Cathodic, anodic and symmetrical drifts of the pH gradient. AB - The production of anodic, cathodic and symmetrical drifts of a pH 3.5-10 gradient formed by isoelectric focusing in polyacrylamide gels is demonstrated experimentally by manipulation of the electrolyte concentrations. Experimental behavior is reproduced by computer simulation of a model mixture of 15 hypothetical carrier ampholytes whose pIs span the pH range 3-10. The mechanism which produces the drifts is elucidated and approaches to minimize such drifts are discussed. The data suggest why most experimentally observed drifts are cathodic. PMID- 2257844 TI - Recent advances in capillary electrophoresis of proteins, peptides and amino acids. AB - The current status of high-performance capillary electrophoresis as an analytical separation method for proteins, peptides and amino acids is assessed. Recent advances in suppressing the effects of electroosmotic flow and irreversible adsorption of proteins at the capillary wall are reviewed, together with procedures for optimal separations of peptides and amino acids. The detection aspects emphasize the role of laser-induced fluorescence and capillary electrophoresis/mass spectrometry in high-sensitivity measurements. PMID- 2257845 TI - Applications of capillary electrophoresis for industrial analysis. AB - Capillary electrophoresis techniques, particularly isotachophoresis and zone electrophoresis, are useful for the determination of various analytes in a wide range of sample matrices. This paper reports applications of capillary electrophoresis developed for detergent, food additive, herbicide, animal nutrition and biotechnology samples. Major advantages of capillary electrophoresis include versatility and speed of method development. Options for small ion analysis using modern, fused silica capillary instruments are discussed. PMID- 2257846 TI - Enantiomer resolution by using capillary zone electrophoresis: resolution of racemic tryptophan and determination of the enantiomer composition of commercial pharmaceutical epinephrine. AB - The enantiomers of D- and L-tryptophan were separated by capillary electrophoresis, using alpha-cyclodextrin as a chiral active component in the background electrolyte. The separation of (-) and (+) epinephrine was achieved by supplementing the background electrolyte with Heptakis (2,6-di-O-methyl-beta cyclodextrin). As a practical application of the method, the quantitative analysis of (-) and (+) enantiomers in commercial pharmaceutical solutions of adrenaline is shown. PMID- 2257847 TI - Capillary electrophoretic determination of S-carboxymethyl-L-cysteine and its major metabolites in human urine: feasibility investigation using on-column detection of non-derivatized solutes in capillaries with minimal electroosmosis. AB - The capillary electrophoretic analysis of S-carboxymethyl-L-cysteine and some of its metabolites in human urine is reported using (i) on-column detection of underivatized solutes, (ii) minimal sample pretreatment and (iii) capillary columns with minimized electroosmosis. Experimental results obtained with two apparatus, the HPE-100 (Bio-Rad), featuring coated fused silica capillaries of 25 microns i.d., and with the Tachophor 2127 (LKB), having Teflon capillaries of 500 microns i.d. are discussed. Drug concentrations down to 0.2 mg/mL on capillary isotachophoresis and 0.03 mg/mL on capillary zone electrophoresis can be monitored with these instruments. PMID- 2257848 TI - The use of metal ion-supplemented buffers to enhance the resolution of peptides in capillary zone electrophoresis. AB - The potential of metal ion-containing buffers to enhance the resolution of peptides in capillary zone electrophoresis was evaluated. The impact of adding Cu(II) and Zn(II) salts to electrophoresis buffers is shown to affect the migrational behavior of several dipeptides containing histidine. Interaction with a metal ion differentially decreases the electrophoretic mobilities of peptides which comigrate in the absence of metal ions, thus causing their separation. This effect is obtained at low pH where the large net charge on the samples yields short analysis times. The dependence of the resolution on Zn(II) concentration is presented for two different samples. The influence of the background buffer is discussed. PMID- 2257849 TI - Separation of cationic proteins via charge reversal in capillary electrophoresis. AB - Analysis of proteins by capillary electrophoresis requires strategies which minimize coulombic interactions with the capillary surface. Thus buffers with pH's above the isoelectric points (pI) of proteins, or near the pI of silanol are required for efficient separation. Covalent modification of the capillary surface is also effective; however, this strategy is technically difficult, abolishes endosmotic flow and suffers from the inherent lability of the siloxane bond. Finally, "dynamic coating" agents, which interact weakly with the capillary surface and therefore, must be included in the separation buffer, suffer from the potential interaction of coating agent with analytes, altering the selectivity of the system. In the following paper, we describe another approach which overcomes all of these difficulties, and demonstrate the ease of use, nondenaturing property, stability and selectivity of the coating strategy with several model protein systems. PMID- 2257850 TI - Capillary zone electrophoretic separation of cyclodextrins with indirect UV photometric detection. AB - A method for the separation of cyclodextrins by capillary zone electrophoresis with indirect detection is described. It is based on the formation of inclusion complexes with benzoate which simultaneously forms a UV absorbing constituent of the background electrolyte used for the separation. PMID- 2257851 TI - Capillary zone electrophoresis of rare earth metals with indirect UV absorbance detection. AB - The separation of 14 lanthanides by capillary zone electrophoresis was studied in the background electrolyte containing hydroxyisobutyric acid as complexing counter-ion and creatinine as a UV absorbing coion for indirect detection of lanthanide zones. A complete separation was achieved in less than 5 min and the applicability of the method for the analysis of real samples was demonstrated. PMID- 2257852 TI - Assay detection limits: concept, definition, and estimation. AB - This paper emphasizes the need for standardizing the definition and estimation of the minimum detectable analyte concentration in an assay. It reviews the key papers that are most frequently quoted in the literature to illustrate the variety of procedures currently in use. PMID- 2257853 TI - Measurement of drug use in a defined population. Evaluation of the defined daily dose (DDD) methodology. AB - To evaluate the accuracy of the DDD per 1000 inhabitants per unit time as an estimate of the fraction of drug users within a population, DDD figures have been compared with the proportion of apparent drug users, i.e. individuals in the population for who a prescriptions had been dispensed. An individual-based prescription monitoring project provided the necessary data for eight drugs representing continuous long-term medication, short-term medication and medication falling in between those two categories. For digoxin, the long-term drug, the number of DDD/1000 inhabitants/day was about 40% below the proportion of apparent drug users. The DDD figure for antibiotics ranged from 4% below to 28% above the apparent users, and for the remaining drugs it ranged from 17% below (bendroflumethiazide, 1982) to 80% below (naproxen, 1985). The DDD methodology is a valuable first step in overall drug use measurement, but for more precise estimates of drug use it must be supplemented by other techniques. PMID- 2257854 TI - Hospital and catchment area antibiotic utilization and bacterial sensitivity in primary infections following gastric surgery in Huddinge, Sweden. AB - The relationship between hospital and catchment area utilization of antimicrobial agents and the antibiotic sensitivity of bacteria isolated from primary infections has been studied after 750 gastric operations performed between 1972 and 1986 at the Huddinge University Hospital. Over 80% of the antibiotics were used in the catchment area. Penicillins (G and V) overall were the most commonly used drugs and comprised 37% of the total antibiotic consumption in 1977-1986. Narrow-spectrum antibiotics dominated throughout the period under investigation. No change in the bacterial resistance to antimicrobial agents was found over time. Many strains of Klebsiella/Enterobacter and E. coli resistant to ampicillin and tetracyclines were recovered throughout the period under investigation. No aerobic Gram-negative bacteria were resistant to gentamicin. All Bacteroides strains except two were sensitive to cefoxitin. Tetracyclines and ampicillin/amoxycillin were mainly used in the catchment area, and cefoxitin and aminoglycosides were almost exclusively used in the hospital. Antimicrobial agents primarily used for out-patients in the catchment area seemed to have more influence on the susceptibility of microorganisms isolated from post-operative infections than agents primarily used in the hospital. PMID- 2257855 TI - Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts. AB - In man ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that ketanserin induces up regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by ketanserin. PMID- 2257856 TI - Dissociation of renal vasodilator and natriuretic effects of dopamine during sulpiride infusion in normal man. AB - The effect of sulpiride on dopamine-induced changes in renal function in man has been investigated. Dopamine dose-response studies were performed in 7 healthy volunteers before and after sulpiride 200 mg i.v. The same investigations were performed in 15 healthy volunteers after pretreatment with the selective alpha-1 adrenoceptor antagonist prazosin (n = 7) and the non-selective alpha-adrenoceptor blocker phentolamine (n = 8). Infusion of dopamine 0.25 to 8 micrograms.kg-1.min 1 resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and a fall in filtration fraction (FF) in 7 normal volunteers. Sulpiride had no effect on base-line ERPF or GFR and did not influence the dopamine-induced renal vasodilatation in those volunteers. It did cause a fall in the fractional sodium excretion (FENa+%) from 1.7 to 1.38, and shifted the dose-response curve of the natriuretic response to a subsequent infusion of dopamine. Sulpiride enhanced the fall in diastolic blood pressure during infusion of dopamine. In 7 other volunteers pretreated with prazosin, sulpiride did not influence base-line ERPF, GFR or FF or their response to dopamine, but the sodium excretion fell markedly (FENa+% changed from 1.13 to 0.63). Administration of sulpiride to 8 volunteers after phentolamine pretreatment 20 mg.h-1 i.v. in the first hour followed by 10 mg.h-1 i.v. resulted in a fall in sodium excretion (FENa+% from 1.09 to 0.53) without affecting ERPF or FF, and it did not affect the dose-response curve in the subsequent DA infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257857 TI - A comparison of the acute effects of cicletanine and bendrofluazide on urinary electrolytes and plasma potassium in essential hypertension. AB - The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257858 TI - The cardiovascular effects of oral nifedipine and nicardipine: a double-blind comparison in healthy volunteers using transthoracic bioimpedance cardiography. AB - The cardiovascular effects of single oral doses of nifedipine (5 and 10 mg) and nicardipine (20 and 30 mg) were compared in a placebo controlled double-blind crossover study involving 8 healthy male volunteers. Two hours following drug administration stroke volume and cardiac index were measured non-invasively using transthoracic electrical bioimpedance cardiography during passive tilting, graded bicycle exercise, and recovery from exercise. Two separate experiments were performed in the absence of active drug to allow the reproducibility of the measurements to be assessed. Coefficients of variation (within experiment/between experiments) for cardiac index were 7.0%/19.9% at rest and 11.5%/9.3% at 180 W exercise. Both nifedipine and nicardipine increased stroke volume and cardiac index and reduced total peripheral resistance (mean blood pressure/cardiac index) at all times in the experiment. Reductions in peripheral resistance were similar for nifedipine 10 mg and nicardipine 20 mg but in these doses slightly larger increases in heart rate were produced by nifedipine, and in stroke volume and cardiac index with nicardipine. The study shows that the cardiovascular effects of nifedipine and nicardipine can be detected using impedance cardiography which is a simple, safe, and inexpensive technique. The differences between the effects of the two drugs were small. Although some were of statistical significance and are consistent with a less marked cardiodepressant effect for nicardipine, the clinical importance of these observations is uncertain. Further studies to examine the effect of oral nifedipine and nicardipine in patients with impaired ventricular function may be helpful in clarifying this tissue. PMID- 2257859 TI - Once-daily theophylline in the treatment of nocturnal asthma. AB - The efficacy and side-effects of individually adjusted doses of controlled release theophylline given once daily in the evening (average dose 650 mg) were compared with those of standard treatment with controlled-release terbutaline 7.5 mg b.d. Thirty-six asthmatics with regular morning obstruction ("morning dipping") were studied over two treatment periods each of two weeks, according to a crossover, randomized, double blind design. Morning peak expiratory flow (PEF) was slightly but significantly higher with theophylline (363 l.min-1) than terbutaline (342 l.min-1). Feelings of dyspnoea on waking in the morning were also less pronounced with theophylline. There were no other differences between the treatment periods during the day or night, with respect to dyspnoea or any the other symptoms. Side-effects were mild and were reported with similar frequencies during both treatments. It is concluded than an individually adjusted dose of once-daily theophylline administered in the evening is at least as effective as conventional therapy with controlled-release terbutaline in preventing nocturnal and early morning asthma, when both drugs are added to regular medication with inhaled sympathomimetics and steroids. PMID- 2257860 TI - Paracetamol test: modification by renal function, urine flow and pH. AB - Factors which might affect paracetamol disposition have been studied in a heterogenous group of patients in need of mild analgesia in an intensive care unit. Following oral administration of 1 g of paracetamol, plasma and urinary concentrations of the parent compound and metabolites were assessed by HPLC. The renal clearance of paracetamol was significantly correlated with urine flow (r = 0.84) and creatinine clearance (r = 0.77), but not with urine pH. Metabolite output was diminished in patients with reduced renal function. Despite the heterogeneity of patients and the diversity of drug treatment, the urine to plasma paracetamol concentration ratio appeared remarkably constant in patients with normal renal function (9.8 +/- 2.7). It is concluded that the metabolite to paracetamol ratio may only be regarded as a measure of the drug metabolizing capacity in subjects with normal renal function, if factors influencing urine volume and paracetamol absorption are standardized. PMID- 2257861 TI - Predictability and intraindividual variability of serum theophylline concentrations in patients with obstructive lung disease: 12-h versus 24-h dosing. AB - The predictability and intraindividual variability of serum theophylline concentrations (STC) after different dosing schedules were investigated in 24 patients with chronic obstructive lung disease (COLD). Three oral regimens were compared in 3 groups of 8 randomly assigned patients. Group I:Drug A once daily in the evening; Group II: Drug A b.d.; Group III: Drug B b.d. The doses for each patient were estimated by Bayesian forecasting aiming at an STC of 10-15 mg/l. STC and FEV1 were measured on two consecutive days at steady-state. The day-to day variability of STC was less than 20% in all three groups. The within-day fluctuation in Group I amounted to 259% (median) compared to 57% and 38% in Groups II and III, respectively. Dose adjustment by Bayesian forecasting resulted in a therapeutic STC in most patients with a b.d. regimen, whereas for the once daily dose the prediction was not satisfactory. No difference in lung function was found between the 24-h and 12-h dosing, probably because of the large intersubject variability in FEV1. Therefore, the question whether the differences in STC profile are of clinical importance in COLD can only be investigated in a larger group of patients. PMID- 2257862 TI - Effects of low-dose prednisolone on cyclosporine pharmacokinetics in liver transplant recipients: radioimmunoassay with specific and non-specific monoclonal antibodies. AB - The following study of cyclosporine pharmacokinetics was performed to investigate the effects of withdrawal of low-dose maintenance prednisolone (0.3-0.6 mg/kg body weight) from the routine immunosuppressive regimen given to 10 liver transplant recipients with stable liver function tests. After oral administration of cyclosporine (6.4-10.3 mg/kg) whole blood concentrations were measured by radioimmunoassay (RIA) with both a specific monoclonal antibody detecting parent drug and a non-specific antibody additionally detecting a cross-section of metabolites. Withdrawal of prednisolone produced no significant change in the mean time and concentration of maximum blood cyclosporine (3.3 h and 1160 micrograms/l, respectively), the initial and terminal elimination half-life (3.5 h and 18.4 h, respectively) and the area under the blood concentration versus time curve (AUC) measured with either the specific or non-specific monoclonal antibody. Measurements with these two antibodies indicated that the terminal elimination of cyclosporine metabolites was more rapid than for the parent drug (half-life: 14.5 vs 18.4, respectively). PMID- 2257863 TI - The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon. AB - We have studied the pharmacokinetics of phenprocoumon with and without co administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 micrograms.h.ml-1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucuronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites. PMID- 2257864 TI - A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients. AB - The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 micrograms/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre dose/peak range of 1-12 micrograms/ml. The pre-dose/peak ranges for the young and old patients were 4-10 micrograms/ml and 4-8 micrograms/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen. PMID- 2257865 TI - Excretion of azapropazone in human breast milk. AB - The excretion of azapropazone in breast milk was studied in four lactating women over one dosing interval following repeated doses of 600 mg b.d. for at least three days. Plasma and milk samples were collected up to 12 hours after drug intake. An average of 0.8 mg azapropazone was calculated as being excreted in breast milk in the 12 hour period. The breast fed neonate would ingest 0.2 mg/kg during this period. PMID- 2257866 TI - Pharmacokinetics of oral noscapine. AB - The relative bioavailability in 20 healthy volunteers of 100 mg, 200 mg and 300 mg tablets of noscapine and 200 mg as a solution has been assessed in a four-way cross-over study, with repeated administration of the 200 mg dose to assess intraindividual variability. There was a disproportionate increase in the AUC of noscapine tablets, as a 3-fold increase in dose produced a 9-fold rise in AUC. This dose-dependency could mainly be attributed to saturable first-pass metabolism of the drug. Administration of noscapine as a solution resulted in a significantly higher maximal concentration at an earlier time-point and a higher AUC than the corresponding dose as tablets. Repeated administration of noscapine tablets and solution yielded higher AUC on the second dosing occasion. No cause for this carry-over effect was found, and the contribution of remaining noscapine was negligible. The terminal half-life of noscapine, which was independent of formulation or dose size was 4.5 h. Both inter- and intraindividual variability in noscapine kinetics were very high, e.g. 73% and 51% CV of the AUC for the 200 mg tablet. PMID- 2257868 TI - Comparison of 500 spontaneous and 500 published reports of adverse drug reactions. AB - The information and case quality of 500 spontaneous and 500 published adverse drug reaction (ADR) reports were compared, including a study of the most common criteria used in different causality assessment methods. The criteria were more often of positive value in the published reports. Nevertheless, spontaneous reports play an important role in the detection of new ADRs. PMID- 2257867 TI - Comparison of the efficacy and systemic effects of 4 mg and 8 mg formulations of salbutamol controlled release in patients with asthma. AB - The purpose of the present study was to compare the efficacy and systemic effects of 4 mg and 8 mg doses of salbutamol controlled release (SCR) after single dosing and at steady state in patients with asthma. Fifteen asthmatic patients (Age 36 y, FEV1 85% predicted) were given SCR 4 mg and 8 mg twice daily for 7 days in a randomised double-blind cross-over design, with at least 7 days washout between treatments. There were no differences between the bronchodilator effects of 4 mg and 8 mg doses. There was no evidence of tolerance to the bronchodilator effects after chronic dosing. Morning and evening PEFR measurements also showed improvements during treatment with SCR 4 mg and SCR 8 mg, although there were no differences between the two formulations. Both doses of SCR caused significant objective tremor responses which were maintained after chronic dosing. The 8 mg dose produced a larger tremor response after single dosing, but not at steady state. Subjective tremor occurred in 7 patients with SCR 8 mg, and in 2 patients with SCR 4 mg. There were no cardiac arrhythmias on Holter ECG monitoring. These results suggest that the 8 mg dose of SCR was no more effective than the 4 mg formulation, and was associated with more systemic adverse effects. PMID- 2257869 TI - Effect of chronic ketanserin treatment on serotonin-induced platelet aggregation in patients with Raynaud's phenomenon. AB - To investigate whether the variable efficacy in Raynaud's phenomenon of long-term oral ketanserin treatment might be related to variation in the sensitivity of 5 HT2 receptors to ketanserin, serotonin-induced platelet aggregation was measured in ten patients with Raynaud's phenomenon at various times after treatment with ketanserin. Platelet aggregation was completely inhibited 90 min after 40 mg ketanserin, but not 12-14 h after the last dose of 40 mg on the 31st day of continuous twice daily administration. However, 90 min after an additional dose of 40 mg, platelet aggregation was again completely inhibited. The present results indicate that ketanserin 40 mg b.d. does not continuously inhibit platelet 5-HT2 receptors in patients with Raynaud's phenomenon and suggest that more frequent intake might be more effective. PMID- 2257870 TI - Effect of acute and prolonged treatment with propranolol on cerebral blood flow and cerebral oxygen metabolism in healthy volunteers. AB - The effect of acute and long-term treatment with propranolol on cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2) has been studied in 8 young healthy volunteers. CBF was measured by 133Xe-inhalation and single photon emission computer tomography, and CMRO2 was calculated from the arterio venous oxygen difference and CBF. Studies were done before and 1 h after i.v. injection of 5 mg propranolol and after three weeks on oral propranolol 80 mg/d for 1 week and 160 mg/d for 2 weeks. Cerebrovascular CO2 reactivity in terms of the A-V oxygen difference was tested on all three occasions during hypercapnia and hyperventilation. CBF, CMRO2 and cerebrovascular CO2 reactivity remained stable both after acute and after 3 weeks of treatment with propranolol. PMID- 2257871 TI - Inotropic effects of ranitidine. AB - The purpose of this controlled study was to study the effect of cimetidine and ranitidine on the myocardium of 8 healthy male volunteers using systolic time intervals. Ranitidine caused a significant decrease in the QS2I, as from 40 min indicating a positive inotropic effect. There were no significant changes in heart-rate or blood-pressure. It is postulated that ranitidine, differing structurally from cimetidine, may have a higher affinity for H2-presynaptic receptors at the sympathetic myocardial junction resulting in an increase in noradrenaline and an increased inotropic effect. PMID- 2257872 TI - A comparison of the anticholinergic effects of two formulations of disopyramide in healthy volunteers. AB - Eight healthy male volunteers took a single oral dose of one of the following: Rythmodan (conventionally formulated disopyramide) 150 mg; Rythmodan 250 mg; Rythmodan Retard (controlled-release disopyramide) 250 mg; placebo. The subjects were allocated double-blind to sessions and treatments according to a Latin square design. In each session pupil diameter, heart rate, salivation, and QT interval were measured immediately before and at 1, 2, 3, 4, 6, 8, and 24 h after the drug. QT interval was corrected for heart rate (QT60). Plasma concentrations of total and unbound disopyramide were also determined at each time point. Both formulations of disopyramide reduced salivary output and increased QT60 interval, but there was not significant difference between the effects of the three active treatments. Neither formulation had any effect on pupil diameter or heart rate. The peak plasma concentration of unbound disopyramide was reached 2 h after Rythmodan and 4 h after Rythmodan Retard. The peak plasma concentration of disopyramide was significantly lower after Rythmodan Retard 250 mg than after Rythmodan 250 mg. The plasma concentration of unbound disopyramide was positively correlated with the reduction in salivation and prolongation of the QT60 interval. The reduction in salivation is likely to reflect blockade of muscarinic receptors by disopyramide, whereas the increase in QT60 interval is likely to be related to a direct effect of the drug on the heart. The results of this single dose study do not indicate that disopyramide in the controlled-release formulation would be better tolerated by patients than conventionally formulated disopyramide. PMID- 2257873 TI - Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers. AB - The influence of food intake on the bioavailability of metoprolol from an OROS system has been investigated. No significant difference was found between OROS administration to fasting subjects or after breakfast in any of the kinetic parameters (AUC, Cmax, tmax, C24 and lag time). Therefore, metoprolol OROS can be administered with breakfast. PMID- 2257874 TI - The probability of G1 cells to enter into S increases with their size while S length decreases with cell enlargement in Allium cepa. AB - The distribution of cell surface area projection (cell size) has been measured at birth and at initiation of DNA synthesis in steady-state populations of Allium cepa root meristems. The conditional probability, P(I/G1), that initiation occurs given that the event of being in G1 also occurs has been estimated from these data. P(I/G1) was found to increase when cells became larger. The distribution of G1 duration has been constructed from indicated cell size distributions. The absolute frequencies of G1 times showed a maximum in the zone of cells with short G1 periods; about 14% of cells appear to enter into S with G1 congruent to 1 h. These results suggest that the increase of P(I/G1) was due to cell enlargement and not to cell aging. By comparing the cell size distribution at initiation of S and at the end of this period, a drastic reduction of cell size variability during DNA replication was observed and both curves were seen as rather similar in shape although they obviously had different modal points. These observations support that there is a negative correlation between the initiation size and the duration of genome duplication, and that cells which initiate DNA synthesis with the same size have a similar replication time. From this hypothesis, a plot of S duration versus cell size at initiation of this period was constructed by comparing the distributions of cell size at start and end of replication; this plot was also consistent with the existence of a negative correlation between cell initiation size and S length. PMID- 2257875 TI - Shuttling of the autoantigen La between nucleus and cell surface after uv irradiation of human keratinocytes. AB - During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors. PMID- 2257877 TI - Catenin association with E-cadherin changes with the state of polarity of HT-29 cells. AB - Cadherins are transmembrane glycoproteins that mediate the calcium-dependent adhesion of cells to one another. It has been reported that at least two and probably more proteins associate with cadherins in various systems. These proteins have been called catenins. HT-29 cells can be manipulated to express either a polar or a nonpolar phenotype, depending on the growth conditions. We have taken advantage of this feature of HT-29 cells to explore the role catenins may play in cadherin-mediated adhesion. In this paper we report that several catenins co-immune-precipitate with E-cadherin in cultured human cells (HT-29 and JAR PR497) and that the nature of the complex of proteins varies with the physiological state of the HT-29 cells. In addition, we show data suggesting that the proteins that associate with calcium-dependent adhesion molecules may represent a group of proteins, some of which are present in all cells and some of which are cell-type specific. PMID- 2257876 TI - Decreased stability of DNA in cells treated with alkylating agents. AB - A modified highly sensitive procedure for the evaluation of DNA damage in individual cells treated with alkylating agents is reported. The new methodology is based on the amplification of single-strandedness in alkylated DNA by heating in the presence of Mg2+. Human ovarian carcinoma cells A2780 were treated with nitrogen mustard (HN2), fixed in methanol, and stained with monoclonal antibody (MOAB) F7-26 generated against HN2-treated DNA. Binding of MOAB was measured by flow cytometry with indirect immunofluorescence. The maximal difference in fluorescence between untreated and HN2-treated cells was observed after heating at 100 degrees C for 5 min in PBS containing 1.25 mM MgCl2. Higher concentrations of MgCl2 inhibited MOAB binding to HN2-treated cells and heating at lower concentrations induced binding to control cells. Intensive binding of MOAB to control and drug-treated cells was observed after heating in Tris buffer supplemented with MgCl2. Thus, the presence of phosphates and MgCl2 during heating was necessary for the detection of HN2-induced changes in DNA stability. Fluorescence of HN2-treated cells decreased to background levels after treatment with single-strand-specific S1 nuclease. MOAB F7-26 interacted with single stranded regions in DNA and did not bind to dsDNA or other cellular antigens. Specific reactivity of MOAB F7-26 with deoxycytidine was established by avidin biotin ELISA. Single-stranded conformation was necessary for the binding of MOAB to deoxycytidine on the DNA molecule. It is suggested that alkylation of guanines decreased the stability of the DNA molecule and increased the access of MOAB F7 26 to deoxycytidines on the opposite DNA strand. PMID- 2257878 TI - The regulation of G0-S transition in mouse T lymphocytes by polyamines. AB - While the role of polyamines in DNA synthesis during the S phase of the cell cycle has been repeatedly postulated, recent studies point also to polyamine involvement in the early phase of the G0-S transition. In order to determine polyamine-dependent steps in the cell cycle we have studied the effects of inhibitors of polyamine biosynthesis and exogenous polyamines on the proliferation of T lymphocytes as well as on the expression of some growth regulated genes. The ability of Con A-stimulated mouse T lymphocytes to enter DNA synthesis was markedly inhibited by methylglyoxal bis(guanylhydrazone) in a dose dependent manner. This inhibitory effect was stronger in the presence of fetal calf serum containing a high level of activities of polyamine oxidases than in the presence of horse serum. Putrescine and spermine added to T splenocyte culture instead of mitogen-Con A stimulated [3H]thymidine incorporation with kinetics similar to that observed with Con A. The growth-stimulating effects of polyamines were concentration-dependent. Polyamines at optimal growth-stimulating concentrations (10 microM spermine and 80 microM putrescine) induced the expression of genes encoding the cytoskeletal proteins beta-actin, vimentin, and alpha-tubulin to an extent and with kinetics similar to those of Con A. The results presented herein suggest that polyamines are capable of stimulating the transition of G0 cells to the S phase and that this effect may be mediated by their influence on the gene expression. PMID- 2257880 TI - Secretory organelle docking at the cell membrane of Paramecium cells: dedocking and synchronized redocking of trichocysts. AB - We present the first evidence that secretory organelle docking at the cell membrane can be reversed in vivo. In nondischarge (nd) mutants of Paramecium tetraurelia all trichocysts can be detached from the cell surface within 2-3 h by different means, including cytochalasin B (but not D), high cell density, or Ca2+ ionophores. Considering the well-established ultrastructural differences between nd and wild-type (wt) cells, one can conclude that trichocyst docking at the cell periphery involves two docking sites (I, II): Site I ties the organelles to the epiplasm, and site II is the connection to the cell membrane at the fusogenic zone (expressed only in wt cells); both sites are close to the cell surface and only 150 nm apart. When the trigger for detachment of cortically docked trichocysts (high cell density, cytochalasin B) is relieved, trichocysts are synchronously reattached at the cell membrane, within 40-50 min, with a rate of 20-40 organelles/min, which far exceeds spontaneous docking rates. This is therefore also the first report on synchronization of secretory organelle docking. It is shown by radioactive leucine labeling that the same organelles are redocked, because trichocyst biogenesis is minimal under the conditions of de/redocking used. Surprisingly not only redocking but also detachment of trichocysts from the cell surface can be abolished by inhibitors of protein synthesis. Since Ca2+ ionophores mimic the effects of other conditions sufficient to detach trichocysts from the cell surface, we assume that a protein-dependent mechanism sensitive to Ca2+ (or other ions in exchange) may operate in trichocyst detachment. The precise mechanism involved in attachment or detachment of trichocysts remains to be elucidated. PMID- 2257879 TI - Differential association of membrane-bound and non-membrane-bound polysomes with the cytoskeleton. AB - We report here a differential release of specific mRNAs from the cytoskeleton by cytochalasin D treatment. Non-membrane-bound polysomal mRNAs, such as histone mRNA and c-fos mRNA, are readily released from the cytoskeleton of HeLa cells during cytochalasin D treatment. Over 90% of H3 and H4 histone mRNA is associated with the cytoskeleton in control cells and only 25% in cells treated with cytochalasin D (40 micrograms/ml). In contrast, the membrane-bound polysomal mRNAs for HLA-B7 and chorionic gonadotropin-alpha are inefficiently released from the cytoskeletal framework by cytochalasin D alone; approximately 98% of the HLA B7 mRNA in control cells is associated with the cytoskeleton, whereas approximately 65% of the HLA-B7 mRNA is retained on the cytoskeleton in cells treated with cytochalasin D (40 micrograms/ml). Disruption of polysome structure with puromycin during cytochalasin D treatment results in the efficient release of HLA-B7 mRNA from the cytoskeleton. Under these conditions, only 25% of the HLA B7 mRNA remains associated with the cytoskeletal framework. Thus, membrane-bound polysomes appear to be attached to the cytoskeleton through a cytochalasin D sensitive site as well as through association with the nascent polypeptide and/or ribosome. These results demonstrate a complex association of polysomes with the cytoskeleton and elements of the endoplasmic reticulum. PMID- 2257881 TI - TGF-alpha and TGF-beta expression during sodium-N-butyrate-induced differentiation of human keratinocytes: evidence for subpopulation-specific up regulation of TGF-beta mRNA in suprabasal cells. AB - Sodium-N-butyrate (NaB) induces terminal differentiation and cornified envelope formation in cultured human keratinocytes. In the present study we explored the question of whether NaB-induced maturation could be mediated through changes in TGF-alpha and TGF-beta expression in normal keratinocytes. NaB induced a four fold increase in TGF-beta mRNA transcript levels. This increase in TGF-beta mRNA abundance occurred only within the nonbasal keratinocyte subpopulation which maximally responds to NaB treatment by progression to cornified envelopes. Basal keratinocytes, which are relatively refractive to cornified envelope formation, did not show any increase in TGF-beta mRNA abundance after NaB treatment. By comparison, TGF-alpha mRNA transcript and extracellular TGF-alpha protein levels were unaffected by NaB treatment. A 50% decrease in EGF receptor binding was observed in NaB-treated keratinocyte cultures, rendering the cells less responsive to proliferation induction. PMID- 2257882 TI - Differences in aggregation properties and levels of the neural cell adhesion molecule (NCAM) between islet cell types. AB - Cells within rat islets of Langerhans are typically organized as a core of B cells, surrounded by the other cell types. When mixed in culture, primary islet cells and insulinoma (RIN2A) cells form aggregates where B-cells are centrally located, surrounded by non-B-cells, while RIN-cells segregate as the outermost layer. To gain insight into the molecular basis underlying this nonrandom cellular organization, the aggregation properties of the three cell populations were studied. Isolated islet cells were separated into B-cells and non-B-cells by autofluorescence-activated cell sorting (FACS). In a short-term aggregation assay, primary B-cell aggregation in the absence of calcium was only 19 +/- 3.7%, compared to the 67 +/- 2.9% seen in the presence of calcium (mean +/- SEM; P less than 0.001; n = 7). By contrast, non-B-cell aggregation and RIN cell aggregation in the absence of calcium (62 +/- 2 and 66 +/- 2%, respectively) were only slightly less than with calcium (70 +/- 3 and 76 +/- 3%). The surface density of the Ca2(+)-independent neural CAM (NCAM) was therefore measured by flow cytometry and found to be 2.64 +/- 0.82-fold higher in non-B-cells, compared to that in B cells (P less than 0.01; n = 3). Even higher levels were found on RIN cells. In the three cell types, NCAM-140 was the only molecular form detected by immunoblotting. In conclusion, differences in the calcium dependency of aggregation and in the levels of NCAM are demonstrated among islet B-cells, non-B cells, and RIN cells. Because cell-cell adhesion is crucial for the maintenance of adult tissue, these aggregation specificities might contribute to the concentric segregation of islet cell types in culture and to the nonrandom distribution of cells within rat islets. PMID- 2257883 TI - The incorporation of myo-inositol into phosphatidylinositol derivatives is stimulated during hormone-induced meiotic maturation of amphibian oocytes. AB - The incorporation of myo-[3H]inositol into phosphatidylinositol and its phosphorylated derivatives was studied by microinjection of the radioactive precursor into Xenopus laevis oocytes. Induction of meiotic maturation of the oocytes by treatment with either progesterone one or insulin resulted in a significant increase in the incorporation of myo-[3H]inositol into the phospholipid fraction. This increase occurred 3-6 h after hormonal treatment, a time coincident with the start of the breakdown of the nuclear envelope, and requires protein synthesis. The effect of progesterone and insulin contrasts with the effect of acetylcholine, which acts through a muscarinic receptor causing the activation of phospholipase C, since the latter effector causes an increase in myo-[3H]inositol incorporation, which is more rapid and does not require protein synthesis. These results suggest that the meiotic maturation process is connected with changes in inositol metabolism in the amphibian oocyte. PMID- 2257884 TI - Enhanced expression of the beta II subspecies of protein kinase C in differentiating erythroleukemia cells. AB - Polyclonal antipeptide antibodies which recognize selected isozymes (alpha, beta I, beta II, and gamma) of the protein kinase C family were used to identify specific subspecies in undifferentiated Friend erythroleukemia cells and in cells triggered to differentiate with hexamethylene bisacetamide. The beta II isozyme of protein kinase C was the primary isozyme expressed and its abundance was significantly increased (P less than 0.05) in differentiated cells. Differences in immunostaining between control and experimental groups were objectively quantitated by determining percentage transmission of light through cells based on color threshold rather than gray intensity levels. Staining was localized to the cytoplasm predominantly in differentiated cells, whereas nuclei stained more intensely in undifferentiated cells. These results provide immunocytochemical evidence to support the hypothesis that changes in the expression of the beta II subspecies of protein kinase C are essential to the programmed maturation of differentiating Friend erythroleukemia cells. PMID- 2257886 TI - Analysis of cis-acting promoter elements using microinjected synthetic oligonucleotides. AB - The transferrin receptor (TR) is expressed in a proliferation-dependent manner that requires transcriptional activation of its gene. Furthermore TR function is required for the DNA synthetic phase of the cell cycle. Oligonucleotides encoding promoter elements within the human transferrin receptor gene were injected into quiescent fibroblasts. The cells were then serum stimulated and the effect of the oligonucleotides on nuclear labeling with [3H]thymidine was determined. Inhibition was observed for oligonucleotides corresponding to a specific region of the promoter. PMID- 2257885 TI - Kinetics of tyrosine phosphorylation and internalization of human EGF receptors overexpressed in NIH 3T3 fibroblasts. AB - Binding of epidermal growth factor (EGF) to cells rapidly induces tyrosine phosphorylation of its receptor which is followed by its internalization and dephosphorylation. The kinetics of these processes differs widely in time from minutes to hours according to cell types. In this paper we analyzed EGF receptor phosphorylation and down-regulation in NIH 3T3 cells transfected with the recombinant hEGF-R cDNA which express 4 X 10(5) receptors/cell. In the presence of EGF receptor phosphorylation reached a maximum after 1 min and was then maintained for about 1 h, while during this time the number of EGF-binding sites was reduced to 40% of the initial number. Detailed analysis of the fate of a population of receptors previously activated and autophosphorylated at 4 degrees C, after warming to 37 degrees C in the absence of the ligand, showed that internalization of the cell surface-associated EGF and dephosphorylation of the receptor were rapid (t1/2 15 min) and followed a similar kinetics. Our data indicate that at any given time only a fraction of the total cell surface receptors is phosphorylated on tyrosine and that dephosphorylation occurs at the cell surface or very rapidly after internalization. In addition the data also suggest that a certain recycling of previously internalized receptors may occur in these cells during EGF treatment. PMID- 2257888 TI - Age population distribution of erythrocytes in young and old healthy donors. AB - Reports from several laboratories on a shorter life span of erythrocytes (E) in old animals and humans, induced the authors to search for a simple method for determining the younger age distribution of E in the blood of 20 old (over 70), as compared to 20 young (below 40), healthy donors. The following tests were performed: 1) Density Distribution of Cells (DDC), 2) Osmotic Fragility, 3) Agglutinability of E by Poly-L-lysine, 4) Analysis of Aspartate Amino Transferase (AST) activity, 5) Test for the presence of immunoglobulin on the surface of E (rosette formation on K562 cells); and 6) All the usual clinical and hematological tests were performed in order to avoid pathology. The most significant difference between the blood of the young and the old was found in the DDC. The shift of the cumulative curve indicated a younger population of cells in the blood of the elderly. The activity of AST was higher in the blood of the elderly, also indicating a younger cell population. The rosette formation was higher with the E from the blood of the elderly, indicating that the E, had more immunoglobulins on their surface than the E from the blood of the younger donors. PMID- 2257887 TI - A purified cellular extract accelerates the cell cycle in Physarum polycephalum. AB - Plasmodia of the myxomycete Physarum polycephalum (strain Cl) were collected at different times during the cell cycle and extracts were prepared from homogenates using a buffer optimized for microinjection into plasmodial veins. These extracts were injected into plasmodia during the first 3 h of the cell cycle. The time of the following mitosis was monitored and compared with that of the buffer-injected controls. Extracts of plasmodia homogenized 45 min before late telophase accelerated the onset of mitosis in the injected plasmodium up to 70 min, i.e., an advance of 10-14% compared to the 8- to 10-h cell cycle duration of the controls. The accelerating activity vanished completely after heating, freezing, or protease digestion, thus indicating the peptide nature of the active agent. Purification of the active compound by means of gel filtration revealed a molecular mass of about 2500 Da. The active portion of the extract was further fractionated by HPLC and the activity determined in a single peak. PMID- 2257889 TI - Fingernail growth rate as a biomarker of aging in the pigtailed macaque (Macaca nemestrina). AB - Rate of fingernail growth (FNG) of the middle digit of the right hand was assessed in 46 healthy pigtailed macaques at approximately 6-month intervals for 4 to 6 years. Mean FNG for 24 females, ranging in mean age at measurement from 7 to 24 years, was 104 mu/day; the mean for 22 males, ranging from 7 to 20 years, was 111 mu/day. Longitudinal analysis showed that FNG declined in animals of both sexes and that the rate of decline (-4.8 mu/day/year) did not differ between them, i.e., the mean regression coefficients (beta) of the two sexes were significantly different from zero and not significantly different from each other. Results of cross-sectional analysis differed from those of longitudinal analysis in that the mean FNG appeared to be more rapid in males than in females, particularly in the older animals. Inter- and intra-individual variability in FNG did not increase with age. FNG appears to be an excellent functional marker of the rate of aging because the direction of change is essentially decremental, a significant degree of change can be detected in a few years, and the rate of change is relatively constant across the adult lifespan. In addition, measurement of FNG is innocuous, quantitative, inexpensive, and simple. PMID- 2257890 TI - Longevity and age-related pathology of LVG outbred golden Syrian hamsters (Mesocricetus auratus). AB - A colony of male Lakeview Golden (LVG) Syrian hamsters has been maintained for the last nine years as a source of various tissues for cellular aging studies. Observations on this colony also yielded data on survival time and physical and pathological manifestations of aging in this strain. Based on 150 spontaneous deaths, the median life span was found to be 19.5 months. The maximum life span was 36 months and the minimum 6 months. A cross-sectional pathological survey of sacrificed and spontaneously dying members of the population revealed a low rate of neoplasia and a variety of degenerative lesions that increased with age. These observations of a varied pathology and a low frequency of neoplasia provide justification for the continued development of the male LVG Syrian hamster as an animal model system for use in studies on the mechanism of both in vivo and in vitro aging. PMID- 2257891 TI - Effects of underfeeding and refeeding on GH and thyroid hormone secretion in young, middle-aged, and old rats. AB - The effects of a 50% reduction in normal food intake for a period of 10 weeks were measured on secretion of growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) in 5 1/2-6 1/2-month old, 13 1/2-month-old, and 17 1/2-18 1/2-month-old male rats. In full-fed controls, GH, T3, and T4 were lower in the old and middle-aged than in the young rats. By the 10th week of underfeeding, GH, T3, and T4 were reduced in all age groups, but the decrease in T3 and T4 in the middle-aged and old rats was greater than in the young rats. Pulses of GH ceased in all the underfed groups. Upon refeeding for 5 days, pulses of GH and levels of GH returned to full-fed control values in the young and middle-aged but not in the old rats. T3 values in the young and middle-aged rats returned to full-fed control levels, but remained below control levels in the old rats. T4 values reached control levels in all age groups upon refeeding. The differences in the response to underfeeding and refeeding by the middle-aged and old rats as compared to the young rats may be due to their initially lower secretion of GH and thyroid hormones and to the age-related decrease in neuroendocrine function. PMID- 2257892 TI - Metabolic heat production during repeated testing at 24 degrees C and 6 degrees C in adult and aged male C57BL/6J mice: the effect of physical restraint before cold stress. AB - Adult (9-14 month) and aged (29-31 month) male C57BL/6J mice were subjected to 3 baseline tests (BASE), 3 cold tests (COLD), or 3 baseline immediately followed by cold tests (BASE/COLD). All tests consisted of partial restraint, and baseline tests were at 24 degrees C for 1 h while cold tests were at 6 degrees C for 3 h. All tests were started at 0900 and were repeated every 2 weeks. Mice were weighed before each test and colonic temperature, O2 consumption, and CO2 production were measured every 4 min for the duration of the test. Mean metabolic heat production during baseline and/or cold and slopes of colonic temperature over time during cold were calculated for each animal. Metabolic heat production at 24 degrees C in both BASE and BASE/COLD was the same in aged mice as adults, however, at degrees C BASE/COLD adult mice increased metabolic heat production compared to 24 degrees C, while aged mice produced a similar amount of heat at both 6 degrees C and 24 degrees C. When comparing metabolic heat production at 6 degrees C between COLD and BASE/COLD mice, adult COLD mice demonstrate an habituation to repeated cold exposure accompanied by increasing heat production, while BASE/COLD adults produce higher heat in all 3 cold exposures. The authors suggest that this is due to a priming of heat production in adults by restraint before the cold. In aged mice, neither COLD nor BASE/COLD groups demonstrate habituation, but BASE/COLD mice produce more heat than COLD during cold exposure, again indicating baseline priming of heat production. The data imply that aged mice have an impairment in specific cold-induced thermogenesis, while their abilities to produce heat in response to restraint-induced sympathetic activation remains intact. PMID- 2257893 TI - Calcium, iron, copper, boron, collagen, and density changes in bone with aging in C57BL/6J male mice. AB - X-rays of old C57BL/6J male mice showed deformed vertebral columns. Bone density was found to increase between 76 and 517 days of age and to decrease after 685 days of age. The boron content of femurs declined by 9% with aging but the decrease was not significant. Calcium increased between 76 and 198 days of age but declined by 36% between 200 and 1000 days of age. Iron increased by 207% by 1000 days of age. Copper declined between 76 and 198 days of age but increased by 61% between 200 and 1000 days of age. Bone collagen as indicated by hydroxyproline and proline content decreased 17.4% by 1000 days of age. The largest single change with aging was, therefore, in the iron content of bone. Several correlations were found to be independent of the age of the animals. Bone density was correlated with bone calcium and collagen. Iron was negatively correlated with calcium and collagen. Calcium and collagen content were unrelated. Bone density and iron were also surprisingly unrelated. A possible explanation for this observation is given. Copper was negatively correlated with bone calcium, bone density, and collagen content. Excess copper was, therefore, the single most important factor associated with decreasing bone size and density. PMID- 2257894 TI - A mathematical model of erythropoiesis suggests an altered plasma volume control as cause for anemia in aged mice. AB - In order to evaluate whether the anemia observed in aged C57B1 and B6D2F1 mice reflects a defect in the control mechanisms regulating erythropoiesis a mathematical model of erythropoietic control is employed, validated previously. In the model it is hypothesized that the most important mechanism for compensating an actual demand of red blood cells is an increase in the mitotic amplification (number of mitoses) of erythroid progenitors (CFU-E, erythroblasts). The same sigmoidal dose-response-relationship between mitotic amplification and hematocrit (Hct) is proposed for young and aged mice. It is mediated by erythropoietin (EPO). Using this relationship one can demonstrate that the expansion of the plasma volume (PV) observed in aged mice is appropriately compensated by an increase in the mitotic amplification of CFU-E and erythroblasts. This implies that aged mice operate in a stimulated state of erythropoietic amplification which is closer to the maximum of the dose-response relationship than the steady state in young mice. This explains the finding of a reduced proliferative reserve in aged mice following further erythropoietic stimulation. An additional analysis regarding the response of aged mice to bleeding anemia is consistent with the view that young and aged mice share the same dose-response-relationship but start from different steady states. These findings suggest that the control mechanisms regulating erythropoiesis in young and aged mice are similar and that the anemia is due to alterations in the PV control. PMID- 2257895 TI - Influence of static head position on the horizontal nystagmus evoked by caloric, rotational and optokinetic stimulation in the squirrel monkey. AB - We studied the influence of static head position on the horizontal nystagmus produced by caloric, rotational and optokinetic stimulation in alert squirrel monkeys. Caloric nystagmus is stronger for nose up (NU) than for nose down (ND) pitches; so, for example, slow-phase eye velocity is four times larger in supine than in prone positions. A similarly directed asymmetry occurs in the horizontal vestibulo-ocular (HVOR) responses to long-duration, constant angular-head accelerations, but not to midband (0.1 Hz) sinusoidal head rotations. Consistent with a first-order model of the HVOR, the low-frequency or acceleration gain of the reflex (GA) is equal to the product of the midband velocity gain (GV) and a time constant (TVOR). GV is proportional to the cosine of the angle between the horizontal-canal plane and the plane of rotation, from which it is concluded that signals from the horizontal, but not from the vertical canals contribute to the HVOR. TVOR can be as much as twice as large in NU than in ND positions. GA is proportional to TVOR and it, too, shows a NU-ND asymmetry. The time constant of optokinetic after nystagmus (TOKAN) was also studied. Since TVOR and TOKAN are modified in similar ways by static tilts, it is concluded that head position affects the time constants by way of velocity-storage mechanisms. Evidence is presented that the position-dependent modification of velocity storage is otolith mediated. The results are used to analyze the mechanisms of caloric nystagmus. The caloric response consists of a convective component (CC), as originally envisioned by Barany (1906), and a nonconvective component (NC). CC accounts for 75% of the caloric response in the conventional supine testing position. Both components can be affected by the position-dependent modification of TVOR or, equivalently, of GA. It has been suggested that two mechanisms might contribute to NC: 1) a direct thermal effect on hair cells or afferents; or 2) a thermal expansion of labyrinthine fluids that results in a cupular displacement. Both theoretical and experimental evidence indicates that only the first of these mechanisms could result in the steady-state caloric response that is observed in the absence of convection (e.g., in spaceflight and after canal plugging) and that contributes to the prone-supine asymmetry seen in caloric testing. PMID- 2257896 TI - Contribution of area 19 to the foreground-background-interaction of the cat: an analysis based on single cell recordings and behavioural experiments. AB - The contribution of area 19 to pattern discrimination in the cat was studied by single cell recordings in this area and by behavioural experiments before and after bilateral lesions. In order to make quantitative comparisons between behavioural performance and that of cell systems, we introduced a new parameter that characterizes visual neurons by their signal-to-noise (S/N) thresholds. A structured visual background made up of Gaussian visual broadband noise which could be moved was superimposed on the signal (moving bars or outline patterns) and the S/N characteristics of the response were determined by varying the signal intensity. The detection performance of cats after bilateral lesion of area 19 showed no deficits. Only for slowly (11 deg/s) or quickly (110 deg/s) moving patterns, or when the background was moved relative to stationary patterns, did we find slight, but significant deficits in the low S/N range. However, when the S/N ratios were higher than 5, all cats achieved their full preoperative performances and no deficits remained. The S/N thresholds of neurons in area 19 were much higher than those found for neurons in areas 17 and 18. The lowest thresholds were found with a stationary background. Introduction of relative velocity between background and bar resulted in intermediate thresholds and the highest thresholds were observed for stimulus configurations lacking relative velocity. These effects correspond to the performance of the intact animal, in which introduction of relative motion increases the performance. The S/N thresholds did not correlate with levels of spike rate recorded at high S/N ratios, direction selectivity or speed preference, indicating that S/N threshold measurements provide a significant additional description of visual neurons. A limited number of area 19 cells recorded in area 17/18 lesioned animals showed very similar thresholds suggesting that this property may be independent of the intactness of areas 17 and 18. The residual performance by 17/18 lesioned cats in detecting small patterns corresponds well to the characteristics of the single cells of area 19. This suggests that area 19 might be able to make a considerable contribution to this task when areas 17/18 are eliminated, though by itself it seems not to be able to sustain the level of performance mediated by them. The contribution of area 19 is restricted to performances at high S/N ratios only.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2257897 TI - ON-OFF units in the mustached bat inferior colliculus are selective for transients resembling "acoustic glint" from fluttering insect targets. AB - Of 311 single units studied in the central nucleus of the inferior colliculus (ICC) in 18 mustached bats (Pteronotus parnelli), a small but significant population (13%) of cells with on-off discharge patterns to tone bursts at best frequency (BF) was found in the dorsoposterior division. In contrast to units with the same BF's but other discharge patterns, the majority of ON-OFF units were unresponsive to sinusoidally amplitude-modulated tone bursts (SAM). To define the contribution of linear and nonlinear components to the responses of ICC neurons to amplitude modulation, we tested some of these neurons with a long, seamlessly repeating pseudorandom sequence of ternary amplitude-modulated tones at BF. Wiener-like kernels were subsequently derived from cross-correlation of spikes with acoustic events in the sequence. These kernels provided estimates of neural impulse responses that proved unusual in SAM-unresponsive ON-OFF units. First, their estimated impulse response had no linear component. Second, the predicted second-order impulse responses to both increments and decrements in stimulus intensity were long (about 20 ms) and nearly identical in shape: triphasic, with the positive phase bounded by leading and trailing negative periods. The similar shape of responses to increments and decrements in these neurons suggests a full-wave rectifier. The triphasic, initially negative second order prediction of the impulse response accounted for an unusual result in experiments measuring the recovery cycle of ON-OFF units using a pair of identical stimulus pulses separated by various time delays. This recovery cycle can be related to their response to amplitude modulation. As the delay between two brief, near-threshold BF tone bursts decreased, the response to the first tone diminished, rather than to the second. The second-order prediction of this experiment derived from impulse responses obtained with pseudorandom noise suggests that, at short interpulse intervals, the initial negative phase of the response to the later stimulus cancels the positive phase of the response to the first. Such cancellation at short interpulse intervals may help explain why the majority of ON-OFF units are unresponsive to SAM. The unusual properties of these ON-OFF units make them ideally suited to respond selectively to infrequent acoustic transients superimposed on an ongoing background of modulation. Such patterns are commonly encountered by mustached bats foraging in cluttered habitats for small, fluttering insects, which generate "acoustic glints" upon a background of modulated echoes from the surroundings (Schnitzler et al. 1983; Henson et al. 1987). PMID- 2257898 TI - Axonal trajectories of inhibitory vestibulocollic neurons activated by the anterior semicircular canal nerve and their synaptic effects on neck motoneurons in the cat. AB - Somatic location, axonal trajectories and synaptic effects of inhibitory vestibulocollic neurons which were activated by selective stimulation of the anterior semicircular canal nerve (ACN) were studied in the anesthetized cat. ACN stimulation evoked disynaptic inhibitory postsynaptic potentials (IPSPs) in neck flexor motoneurons. This was seen in all the (64/64) tested motoneurons innervating the ipsilateral (i-) longus capitis (LC) and the i sternocleidomastoideus (SCM) muscles and in 86% (38/44) of the motoneurons innervating the contralateral (c-) LC muscle. The inhibitory relay neurons, identified by orthodromic and antidromic responses to stimulation of the ACN and the i- and c-LC motoneuron pools, were classified as VCi (vestibulocollic neurons sending an axon to the i-LC motoneuron pool) and VCc (vestibulocollic neurons sending an axon to the c-LC motoneuron pool) neurons. Neither VCi nor VCc neurons were activated antidromically by localized stimulation of the ascending medial longitudinal fasciculus (asc. MLF) or the 3rd nuclei. They were located in the medial, descending and ventral lateral vestibular nuclei. It was also observed that VCi neurons produced unitary IPSPs in i-LC and i-SCM motoneurons in the C1 segment. Inhibitory synapses were estimated to be on the cell somata and/or the proximal dendrites of the motoneurons. PMID- 2257899 TI - Auditory-visual interaction in the generation of saccades in man. AB - Four normal human subjects were investigated for evidence of auditory-visual interaction in the generation of horizontal saccades. In a first experiment it was shown that the mean amplitudes of initial saccades from primary position to auditory targets were significantly affected by the simultaneous occurrence of a distracting visual stimulus. If both auditory and visual stimuli were in the same hemifield, the mean amplitude of initial saccades to a fixed buzzer position was consistently increased or decreased depending on the position of the visual stimulus. The phenomenon is felt to be analogous to the "centre-of-gravity" effect previously described for two simultaneous visual stimuli. It did not occur if visual and auditory stimuli were in opposite hemifields when a simultaneous visual stimulus caused a slight reduction of mean initial saccadic amplitude compared to the mean amplitude to buzzer alone. In this case the reduction was independent of visual stimulus position. Similar effects were seen for mean final eye positions. In a second experiment, a similar procedure was carried out, but the eyes started by looking at a point at 15 degrees eccentricity. The same pattern of auditory-visual interaction was obtained in both experiments, consistent with the concept of eye-movement related movement of modality-specific sensory "maps" which has recently been shown to occur in the superior colliculus of primates. PMID- 2257900 TI - Lateral-posterior and pulvinar reaching cells--comparison with parietal area 5a: a study in behaving Macaca nemestrina monkeys. AB - In a previous study we have demonstrated the existence of pulvinar (puv) cells which were optimally activated when a monkey executed reaching movements with his limbs (Acuna et al 1983). We now describe further observations in four Macaca nemestrina monkeys trained to perform goal directed reaching movements aimed at four different positions in space. Extracellular unit activity in the lateralis posterior (lp) and puv nuclei, together with electrooculograms were recorded during the execution of the task. Seven hundred and sixty neurons were studied in the lp-puv complex. One hundred and twenty three cells (16%) showed changes in activity related to the reaching movements. Reaching related cells fell into two categories: goal direction sensitive (28/123 = 23%) and pandirectional (95/123 = 77%). Goal direction sensitive cells showed different responses depending on the direction of the goal relative to the starting point of the movement. The responses of the pandirectional cells were independent of goal direction. The activity of the remaining cells (637/760) could not be correlated with reaching movements. In a smaller number of area 5a (PE) cells (n = 109) studied in one monkey, 82 (75%) were classified as reaching related cells. Of these, 76% (62/82) were goal direction sensitive and 24% (20/82) pandirectional. The lp-puv cells were more dependent on the intentionality of movement than area 5a cells, and not reliably activated by passive manipulation of the limb. After injection of HRP WGA in area 5a, where the reaching cells were recorded, labeled cells and terminals were located in the lp-puv zones where reaching cells were also found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257901 TI - Postural strategies associated with somatosensory and vestibular loss. AB - This study examines the roles of somatosensory and vestibular information in the coordination of postural responses. The role of somatosensory information was examined by comparing postural responses of healthy control subjects prior to and following somatosensory loss due to hypoxic anesthesia of the feet and ankles. The role of vestibular information was evaluated by comparing the postural responses of control subjects and patients with bilateral vestibular loss. Postural responses were quantified by measuring 1) spatial and temporal characteristics of leg and trunk EMG activation; 2) ankle, knee, and hip joint kinematics, and 3) surface forces in response to anterior and posterior surface translations under different visual and surface conditions. Results showed that neither vestibular nor somatosensory loss resulted in delayed or disorganized postural responses. However, both types of sensory deficits altered the type of postural response selected under a given set of conditions. Somatosensory loss resulted in an increased hip strategy for postural correction, similar to the movement strategy used by control subjects while standing across a shortened surface. Vestibular loss resulted in a normal ankle strategy but lack of a hip strategy, even when required for the task of maintaining equilibrium on a shortened surface. Neither somatosensory nor vestibular loss resulted in difficulty in utilizing remaining sensory information for orientation during quiet stance. These results support the hypothesis that cutaneous and joint somatosensory information from the feet and ankles may play an important role in assuring that the form of postural movements are appropriate for the current biomechanical constraints of the surface and/or foot. The results also suggest that vestibular information is necessary in controlling equilibrium in a task requiring use of the hip strategy. Thus, both somatosensory and vestibular sensory information play important roles in the selection of postural movement strategies appropriate for their environmental contexts. PMID- 2257902 TI - Changes in excitability of motor units during preparation for movement. AB - Single biceps motor units were recorded in two awake monkeys (Macaca fascicularis) during the preparation for and execution of a forearm flexion movement. The motor sequence was organized as follows: after a control period lasting 500 ms, the animal was informed that a preparatory period (PP) was beginning by a preparatory signal (PS) consisting of diffuse sound and light. One to 1.5 s later, the animal was instructed by a bright light response signal (RS) to perform a rapid forearm flexion movement. Two hundred motor sequences were run during each daily session. The single motor units (MU) were recorded and their discharges analysed. In both monkeys, two extreme groups were found to exist on the basis of their pattern of activity during the preparatory and movement execution phases. 56% of the MUs were silent during the PP and showed a brief burst of discharge after the RS, which was strictly correlated to the movement execution. Their high recruitment threshold and their firing frequency during resting and movement periods suggested that these MUs associated with the movement execution could be called presumed fast or phasic MUs. Among the remaining MUs (44%), 15% were active as early as the beginning of the PP (about 300 ms after the PS) and showed a progressively increasing discharge, which stopped just after the beginning of the movement execution. These MUs associated with the preparatory phase had low recruitment thresholds and firing frequencies, which is compatible with the possibility that they might be slow or tonic MUs. Two functional hypotheses can be proposed on the basis of these results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257903 TI - Low threshold calcium spikes in medial vestibular nuclei neurones in vitro: a role in the generation of the vestibular nystagmus quick phase in vivo? AB - Intracellular recordings were obtained from medial vestibular nuclei neurones in guinea-pig brainstem slices. A subpopulation of neurones in this nucleus was found to have burst firing properties. Using ionic channel blockers the underlying mechanism was shown to be a low threshold calcium spike. It is speculated that this property could be implicated in the generation of the quick phase of the vestibular nystagmus in the behaving guinea-pig. PMID- 2257904 TI - Evidence of the co-activation of alpha-motoneurones and static gamma-motoneurones of the sartorius medialis muscle during locomotion in the thalamic cat. AB - The activity in alpha and gamma efferent axon populations and in group I and group II afferent fibre populations innervating a flexor muscle, the sartorius medialis, was observed during spontaneous locomotor movements in the thalamic cat. Multi-unit discharges of each kind of fibre were obtained by electronic sorting of the action potentials from the overall activity of a thin, intact branch of the sartorius medialis nerve. The following results were obtained: (1) The gamma-motoneurones have a phasic behaviour characterized by a single discharge period during the hip flexion (swing phase of the step-cycle). (2) The gamma-motoneurones are co-activated with the homonymous alpha-motoneurones. (3) Between rhythmic alpha and gamma discharges, i.e. during the hip extension (stance phase of the step cycle), both alpha- and gamma-motoneurones were normally silent. However, in 5 out of 17 experiments, a few units of the gamma population fired at very low frequency. (4) Two observations indicate that the gamma-motoneurones that are co-activated with the alpha-motoneurones by central locomotor commands are predominantly of the static type. In actual locomotion, the rhythmic fusimotor discharges over-compensate the depressor effect on the firing rate of the group II afferents of the unloading of muscle spindles by the active shortening of the parent muscle. In fictive locomotion, when the transmission of the excitation is blocked by selective curarization in alpha skeleto-motor junctions alone, the rhythmic fusimotor discharges elicit in-phase modulations not only of the group I but also of the group II fibres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257905 TI - Effects of serotonin releasers on dentate granule cell excitability in the rat. AB - Serotonin modulating effects on hippocampal electrical activity were studied using serotonin releasing drugs (e.g. d-fenfluramine, FFA, and p chloroamphetamine, PCA). FFA and PCA enhanced the reactivity of the dentate gyrus to stimulation of the perforant path (PP) in the anesthetized rat. The population spike (PS) but not the population EPSP (EPSP) was enhanced by FFA indicating that the drug effect is not exerted at the PP synapse, but at some postsynaptic site between the synapse and the spike generation mechanism. A depth profile of the response to PP stimulation indicated that the largest effect of FFA was present just below the granular cell layer. There were no systematic effects of FFA on the EPSP at any depth tested. The effect of FFA was much reduced in rats depleted of serotonin by p-chlorophenylalanine (PCPA) and restored when serotonin stores were repleted by the serotonin precursor 5-hydroxytryptophane (5-HTP). d-FFA was at least twice as effective as 1-FFA in enhancing responses in the dentate gyrus (DG). In noradrenaline (NA) depleted rats the increase in PS size was as in control rats. The effects of FFA were blocked by the 5-HT1a antagonist spiperone but not by the 5-HT2 antagonist mianserin. These results suggest that the effect of FFA is primarily due to release of serotonin from its terminals. At the gross electrographic level, FFA suppressed spontaneous sharp wave activity and reduced the magnitude of hippocampal EEG. Spontaneous extracellular single unit activity, recorded in the DG, was also inhibited by FFA concomitantly with the increase in the PS size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257906 TI - Selective coding of motor sequence in the supplementary motor area of the monkey cerebral cortex. AB - We describe a property of neurons in the supplementary motor area (SMA) of the cerebral cortex of monkey that is different from those in the primary motor area (M1) in relation to execution of a sequential motor task. A group of SMA neurons was active when the animal remembered and pressed three touch-pads in a predetermined sequence but inactive when the same movement was guided by sequentially presented visual signals. This finding indicates that the SMA is involved in the performance of sequential movements on the basis of the information stored inside the brain. PMID- 2257907 TI - Amplitude modulation of the human quadriceps tendon jerk reflex during gait. AB - Amplitude modulation of the quadriceps tendon jerk reflex was investigated during the step cycle in normal human subjects. Reflex amplitude was compared with that obtained during a control stance condition, with "equivalent" levels of EMG activity and limb position. During gait there was a progressive decrease in the reflex amplitude early in the stance phase, i.e. during yielding of the knee, and it remained reduced throughout the step cycle. This pattern of changes in reflex amplitude correlated with neither the quadriceps EMG activity nor with the knee joint movements. The behavior of the tendon reflex was similar to that described for the modulation of the quadriceps H-reflex during the early stages of the stance phase of gait. In the latter study it was argued that changes in presynaptic inhibition of quadriceps la terminals could account for the amplitude modulation. We conclude that there is no dramatic change in the gamma drive to quadriceps muscle spindles: tendon reflexes are modulated during the step cycle in much the same way as H-reflexes, in spite of the peripheral and central differences between them. Similar behavior has been described for the soleus H reflex and Achilles tendon reflex during gait although the modulation of these reflexes followed a different pattern than that seen in the quadriceps. PMID- 2257908 TI - Cortico-cortical connections of two electrophysiologically identified arm representations in the mesial agranular frontal cortex. AB - Neuronal tracers (diamidino yellow or wheat germ agglutinin conjugated with horseradish peroxidase) were injected in the arm representations of area 6a alpha (mesial surface, area F3), in the arm representation of area 6a beta (mesial surface) as well as in the eye field of area 6a beta (dorso-medial surface). The results showed that the arm representation of area F3 receives topographically organized afferents from motor and premotor areas (areas F1, F2, F4 and F5). A further connection was found with that part of cingulate cortex that sends projections to the spinal cord. In contrast, the arm representation of area 6a beta receives afferents chiefly from area F5, the prefrontal cortex and that part of cingulate sulcus which has few, if any, connections with the spinal cord. No connections were found with the precentral motor cortex (area F1). The area 6a beta eye field receives afferents mostly from the frontal eye field. Further connections are with the prefrontal cortex and cingulate gyrus. It is suggested that the so called "low level" motor functions of supplementary motor area are due to the activity of area F3, whereas the so called "high level" motor functions depend upon an independent area located in area 6a beta. PMID- 2257909 TI - An output zone of the monkey primary motor cortex specialized for bilateral hand movement. AB - We have identified a subregion in the monkey primary precentral motor cortex (MI) that is characterized by its relationship to bilateral or ipsilateral hand movements. The subregion is located between the digit and face representation areas. The majority of single cells in this portion of MI exhibit distinct activity before and during visually triggered key-press movements performed by means of ipsilateral or contralateral digit flexion. Intracortical microstimulation evoked responses of ipsilateral, in addition to contralateral, digit muscles. PMID- 2257910 TI - Mono- and disynaptic excitatory inputs from the superior colliculus to vertical saccade-related neurons in the cat Forel's field H. AB - Excitatory inputs to neurons in the Forel's field H (FFH) related to visually induced vertical saccades from the ipsilateral superior colliculus (SC) were investigated in chronically prepared alert cats. By stimulation of the deep or intermediate layer of the SC, upward augmenting neurons (ANs) and one long-lead downward burst neuron (BN) were found to be activated monosynaptically, while medium-lead BNs were activated disynaptically. The monosynaptically activated neurons were not antidromically activated from the oculomotor nucleus, whereas disynaptically activated neurons were also activated antidromically from the inferior rectus subdivision of the nucleus. These results suggest that an excitatory input to the FFH from the SC for inducing vertical saccades of visual origin first reaches upward ANs and/or long-lead downward BNs in the FFH, which in turn drive medium-lead BNs in the same area synapsing with motoneurons related to vertical eye movements. PMID- 2257911 TI - Reductions in recruitment force thresholds in human single motor units by successive voluntary contractions. AB - Recruitment force thresholds of biceps brachii single motor units were studied in 4 male subjects before and after an isometric muscle contraction, passive muscle stretch, or following successive muscle contractions, muscle stretches or during alternations between muscle stretches and muscle contractions. Isometric muscle contractions of 5 s duration decreased subsequent single motor unit force thresholds. These force thresholds could usually be reset at or near precontraction force threshold values by passive muscle stretch induced by elbow extension. Single motor units showing reduced force thresholds following contraction were momentarily derecruited during and/or after muscle stretch. Successive muscle stretches alone did not significantly alter single motor unit force thresholds. In contrast, single motor unit recruitment force thresholds during successive weaker contractions were progressively lowered. Intercontraction muscle stretches maintained the single motor unit force thresholds at or near the initial force threshold level. The mechanism(s) underlying a muscle contraction-induced lowering of single motor unit force thresholds may reside in stretch reflex pathways. PMID- 2257912 TI - Neurons signalling the maintenance of attentive fixation in frontal area 6a beta of macaque monkey. AB - Twelve out of 140 neurons recorded in a restricted region of the frontal agranular cortex (area 6a beta) of trained macaque monkeys, discharged only during attentive fixation of a target in the straight ahead position. These cells, lacking a visual receptive field, were silent when the animal's eye was in the same position during spontaneous oculomotor behaviour. Our preliminary results suggest that this area is involved in the codification of attentive fixation. PMID- 2257913 TI - A specific subgroup of non-length tuned relay cells in the feline dorsal lateral geniculate nucleus. AB - Length tuning was first described for the "hypercomplex cell category" in the visual cortex. However it has subsequently become apparent that cells in the dorsal lateral geniculate nucleus (dLGN) also exhibit a high degree of length tuning and that for the majority of the population this matches or exceeds that associated with cortical hypercomplex cells (Cleland et al. 1983; Jones and Sillito 1987). In this paper we describe a distinct subpopulation of dLGN Y cells that lack length tuning. These cells were also characterised by poor centre surround antagonism, and tended to be located close to laminar borders. They appeared to constitute 25% of the Y cell population. Following recent evidence showing relay cells to be powerfully excited by acetylcholine, and inhibitory interneurones to be inhibited, we have examined the responses of these non-length tuned cells to iontophoretic application of acetylcholine. Their brisk excitatory responses suggest that these cells are in fact relay cells. Their presence raises the possibility of a discrete non-length tuned component to the geniculate input to the cortex, and has potentially important implications for the way in which synaptic processes contributing to the length tuning profiles of visual cortical cells are modelled. PMID- 2257914 TI - Texture discrimination by cells in the cat lateral geniculate nucleus. AB - The spontaneous segregation of texture areas is an impressive perceptual phenomenon, the neural basis of which is not yet understood. In the texton concept (Julesz and Bergen 1983; Julesz 1984, 1986) it is assumed that the visual system analyzes a stimulus for certain features ('textons') the spatial distribution of which is pre-attentively registered and may provide the percept of dissected texture areas. Supposed textons are blobs of a given size, oriented lines, line intersections and line terminators, suggesting that texture analysis is exclusively mediated by form-specific filters at higher, e.g. cortical, processing levels. This paper investigates the contribution of cells in the cat lateral geniculate nucleus (LGN) to segregation of typical texton differences. The results indicate that LGN cells, though not resembling the supposed texton filters, often distinguished textured arrangements of such features on the basis of a variety of other visual cues, such as global or local variations in mean luminance or differences in spatial frequency composition. Thus, cells responded to texture borders between areas differing in the size or the density of texture elements and often revealed differential firing rates to textures differing by the crossing or the terminator feature. For textures with differences in line orientation, however, only small variations of the firing rate were seen. In summary, the observations suggest a means of texture representation in the cat LGN which is different from recent concepts of texture segregation in man. For a given pair of textures, cells with receptive fields larger than, or similar to the texture raster respond to global and local luminance variations between areas and, in particular, to differences in their spatial frequency composition. These cells, hence, may signal the global texture difference without encoding spatial details of the pattern from which texton features could be identified. Cells with receptive fields small in comparison to texture elements transfer all the information necessary for analyzing these elements in detail, but themselves are relatively insensitive to global texture differences. PMID- 2257915 TI - 'Real-motion' cells in area V3A of macaque visual cortex. AB - The stability of visual perception despite eye movements suggests the existence, in the visual system, of neural elements able to recognize whether a movement of an image occurring in a particular part of the retina is the consequence of an actual movement that occurred in the visual field, or self-induced by an ocular movement while the object was still in the field of view. Recordings from single neurons in area V3A of awake macaque monkeys were made to check the existence of such a type of neurons (called 'real-motion' cells; see Galletti et al. 1984, 1988) in this prestriate area of the visual cortex. A total of 119 neurons were recorded from area V3A. They were highly sensitive to the orientation of the visual stimuli, being on average more sensitive than V1 and V2 neurons. Almost all of them were sensitive to a large range of velocities of stimulus movement and about one half to the direction of it. In order to assess whether they gave different responses to the movement of a stimulus and to that of its retinal image alone (self-induced by an eye movement while the stimulus was still), a comparison was made between neuronal responses obtained when a moving stimulus swept a stationary receptive field (during steady fixation) and when a moving receptive field swept a stationary stimulus (during tracking eye movement). The receptive field stimulation at retinal level was physically the same in both cases, but only in the first was there actual movement of the visual stimulus. Control trials, where the monkeys performed tracking eye movements without any intentional receptive field stimulation, were also carried out. For a number of neurons, the test was repeated in darkness and against a textured visual background. Eighty-seven neurons were fully studied to assess whether they were real-motion cells. About 48% of them (42/87) showed significant differences between responses to stimulus versus eye movement. The great majority of these cells (36/42) were real-motion cells, in that they showed a weaker response to visual stimulation during tracking than to the actual stimulus movement during steady fixation. On average, the reduction in visual response during eye movement was 64.0 +/- 15.7% (SD).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2257916 TI - Retrograde transneuronal transport of wheat-germ agglutinin to the retina from visual cortex in the cat. AB - Injections of peroxidase-conjugated wheat-germ agglutinin (WGA-HRP) were made into areas 17 or 18 of cats. After survivals of 3-7 days, foci of HRP-labeled ganglion cells were found at the appropriate topographic locations in the retinas. The labeling was interpreted as resulting from retrograde transneuronal transport through the lateral geniculate nucleus. This phenomenon offers a new and simple technique for the study of retinotopic maps in visual cortex. PMID- 2257917 TI - Head stabilization during various locomotor tasks in humans. I. Normal subjects. AB - Head kinematics were studied in ten normal subjects while they executed various locomotor tasks. The movement of the body was recorded with a video system which allowed a computer reconstruction of motion of joint articulations and other selected points on the body in three dimensions. Analyses focus on head translation along the vertical axis and rotation in the sagittal plane. This was done by recording the displacement of a line approximating the plane of horizontal semi-circular canals (the Frankfort plane: F-P). Four conditions were studied: free walking (W) walking in place (WIP) running in place (R) and hopping (H). In the 4 experimental conditions, amplitude and velocity of head translation along the vertical axis ranged from 1 cm to 25 cm and 0.15 m/s to 1.8 m/s. In spite of the disparities in the tasks regarding the magnitude of dynamic components, we found a significant stabilization of the F-P around the earth horizontal. Maximum amplitude of F-P rotation did not exceed 20 degrees in the 4 situations. Vertical angular velocities increased from locomotion tasks to the dynamic equilibrium task although the maximum values remained less than 140 degrees/s. Predominant frequencies of translations and rotations in all the tasks were within the range 0.4-3.5 Hz and harmonics were present up to 6-8 Hz. During walking in darkness, mean head position is tilted downward, with the F-P always below the earth horizontal. Darkness did not significantly influence the amplitude and velocity of head angular displacement during W, WIP and R, but during H the amplitude decreased by 37%. Residual head angular displacement is found to compensate for head translation during the 4 conditions. Our study emphasizes the importance of head stabilization as part of the postural control system and described as a basis for inertial guidance. PMID- 2257918 TI - Morphological reaction patterns of the human liver during xenobiotic loading. A light microscopic contribution. AB - Xenobiotic load of the liver shows an increasing tendency. This can cause functional and structural lesions of this organ. Among the xenobiotic hepatotoxic agents alcohol and drugs stand in the rank order on the first position: occupational noxes follow. The liver develops different morphological patterns which reach from adaptative to alterative parenchymal changes. Inflammatory reactions of the liver mesenchyma follow which are correlated to the intensity of the parenchymal lesions. In this paper the different light microscopic patterns and the classification of such injuries are demonstrated. PMID- 2257919 TI - Substructural alterations of liver parenchymal cells induced by xenobiotics. AB - Xenobiotic-induced basic ultrastructural reactions of liver parenchymal cells as visualized with the basic method in ultrastructural research, the transmission electron microscopy, are described. There exists no "average hepatocyte", but even the normal liver is composed of a heterogeneous population of parenchymal cells revealing distinct ultrastructural and functional differences according to the intra-acinar location, circadian rhythms or metabolic and physiologic conditions. This liver cell heterogeneity is, as a rule, very much increased after acute or chronic exposure of the liver to any xenobiotic compound. Although most electron microscopic techniques are laborious and time consuming, electron microscopic research will play a growing role in analysing the response of the hepatocytes to drugs or other newly developed chemicals. There is no doubt that new methods and instrumental improvements will enable us to visualize more and more the primary site of action of any xenobiotic and the underlying molecular mechanisms in the hepatocytes followed by a sequence of events which lead to the manifestation of a complex reaction pattern composed of adaptation, injury, degeneration and reparation of the liver. PMID- 2257920 TI - Determination of enzyme activities in serum for the detection of xenobiotic effects on the liver. AB - The determinations of enzyme activities in the serum are of considerable importance in detecting xenobiotic effects on the liver. After a brief introduction to the basics of enzyme diagnostics, the enzymes ALAT, ASAT, ICDH, LDH, SDH, GLDH, AP, gamma-GT, CHE are characterized with regard to their occurrence, their half-life periods in the serum and their clinical value. They are followed by enzyme levels and the presentation of the dynamics of enzyme activities in the serum after xenobiotic influences on the liver in humans. PMID- 2257921 TI - Determination of regional blood flow in abdominal organs and other structures in normal female rats and in rats with TAA-induced chronic liver injury using 99mTc labelled HSA-microsphere technique. AB - A method for simultaneous determination of cardiac output and regional blood flow distribution in a chronically instrumented, unrestrained rat preparation for different experimental conditions (i.e. conscious, free movement; general anesthesia) and in an experimental chronic liver injury model is described. The use of a modified radioactive microsphere reference sample method using 99mTc labelled HSA-microspheres provides valid measurements of cardiac output [255 +/- 21.6 ml/(min.kg b.wt.)] and of the determined blood flow rates of abdominal organs (with separate determination of arterial and portal-venous hepatic blood flow rates; the latter by means of arterial blood flow measurement of the gastrointestinal tract and the spleen), the myocard, the adrenals, the kidneys, and various brain regions. Furthermore, it is demonstrated that this measuring approach with chronical preparation can also advantageously be used in pharmacological or pathogenetical studies, especially because of the simple measuring equipment and the comparatively low costs that offer a broader application. PMID- 2257922 TI - Influence of xenobiotics on bile flow and bile composition in rats- methodological approach. AB - Optimal procedures for the investigation of bile flow and excretion of bile constituents are described, and data are given regarding sex and age dependency, use of narcotic drugs and replacement of water loss in Wistar rats. A combination of ketamine and xylazine can be recommended for anaesthesia. In long time studies saline infusion keeps bile and urine production constant over a period of 6 h. Bile flow and biliary excretion of bile acids and electrolytes are immature at birth and reach a maximum between the 20th and 60th day of life. The biliary excretion of cholesterol decreases with age. The concentrations of bile constituents such as lipids, glutathione, protein, uric acid, urea, osmotically active substances, and steroid hormones are given for adult rats. Bilateral nephrectomy decreases bile flow in mature rats only. PMID- 2257923 TI - Influence of xenobiotics on drug metabolism and its sensitive detection. AB - Biotransformation of drugs and other xenobiotics in the liver plays an important role intoxication and detoxication processes, i.e. changes in biotransformation activity have significant biological consequences. For that reason the determination of biotransformation activity is useful. The rate of some biotransformation reactions can be markedly changed by very small doses of xenobiotics. These changes may be used for the sensitive detection of the exposure to xenobiotics. Among biotransformation reactions cytochrome P-450 dependent monooxygenation is very important. It can be induced and inhibited by xenobiotics. Induction of P-450 forms can be detected by various methods, e.g. by using model reactions. Ethoxycoumarin O-deethylation, ethoxyresorufin O deethylation, pentoxyresorufin O-depentylation and ethylmorphine N-demethylation are catalyzed at different P-450 forms, and their determination is described in detail. PMID- 2257924 TI - Epoxide hydrolase, its function and determination of its activity in rat liver. AB - Epoxides are a group of reactive intermediates formed by the cytochrome P-450 mediated monooxygenation of unsaturated xenobiotics. Epoxide hydrolase inactivates these epoxides by addition of water to form diols. Commonly the function of epoxide hydrolase is finally followed by excretion of the diols. However, reactivation of certain diols by a second epoxidation may happen. Epoxide hydrolase inactivates also the epoxides existing in the metabolism of endogenous compounds. The determination of the activity of epoxide hydrolase by the addition of water to styrene oxide (1,2-epoxyethylbenzene) and measurement of the concentration of the produced phenylglycol (1-phenyl-1,2-ethandiol) with subsequent separation of the 2 substances by HPLC is described. Lipophilic xenobiotics tend to accumulate into tissues, and they must be transformed to water soluble compounds to enable the excretion. In this transformation process reactive intermediates are produced. If biotransformation fails to detoxify these reactive intermediates, they may react covalently with critical targets like the genetic material, or start harmful reaction chains like lipid peroxidation. As a result of this carcinogenicity, mutagenicity etc. may ensue Miller and Miller (1976). Depending on the chemical structure of the molecule, different kinds of reactive substances are generated. Epoxides originate from oxidation of an aliphatic or aromatic double bond by the action of cytochrome P-450-mediated monooxygenases (Leibmann et al. 1979). One detoxifying pathway is the addition of water to form diols, which are of low reactivity; this reaction is catalyzed by epoxide hydrolase. Other possible pathways are the formation of glutathione conjugates or the rearrangement to aldehydes or ketones (Habig et al. 1974; Oesch 1979).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257925 TI - Detection of chemical carcinogens by means of the "rat liver foci bioassay". AB - The rat liver foci bioassay designed as short-term screening test system in vivo is a reliable procedure for the detection of the carcinogenic potential of chemicals. The use of tumor prestages as markers is favorable in many respects: 1. There is a convincing correlation between foci and tumors. 2. The sensitivity is by a factor of more than 1,000 higher compared to the chronic carcinogenicity study. 3. It is the only system available so far for detecting liver tumor promotors. 4. There is promising prospect that carcinogenic agents with extrahepatic target organs can be detected. PMID- 2257926 TI - In vitro and ex vivo effects of the air pollutants SO2 and NOx on benzo(a)pyrene activating enzymes of the rat liver. AB - In the course of a larger project aimed at studying possible combination effects between common air pollutants and carcinogens, previous studies of our laboratory had shown that the genotoxic activity of benzo(a)pyrene (B(a)p) in fetal lung cells of the Syrian hamster is decreased by NOx and SO2. This particular study was performed to assess whether the gases may cause this depression by affecting the net yield of active B(a)p metabolites. Using the S. typhimurium assay as a model-system the gaseous exposure of subcellular activation systems to SO2 and NOx did not affect the yield of B(a)p induced mutants of S. typhimurium. Also the pretreatment of animals with SO2 or NOx in vitro did not result in a measurable induction or inhibition of B(a)p metabolizing enzymes, as was assessed also with S. typhimurium. Accordingly, neither direct enzymic interactions nor complex systemic pathways reflected possible mechanisms of combination effects between B(a)p and the air pollutants. PMID- 2257927 TI - The effects of xenobiotics on hepatic lipid and lipo-protein metabolism. AB - The liver occupies a central position in lipid and lipo-protein metabolism. Its function includes lipid and lipoprotein biosynthesis, assembly, packaging, transport, secretion, uptake and degradation of lipoproteins. In addition, enzymes synthesized and secreted by the liver into the blood stream or remaining bound to the endothelial cells in the capillaries, affect lipoprotein metabolism in the circulation. Xenobiotics may influence each of these steps. The mechanisms include more specific actions such as hormone or transmitter agonism and antagonism, membrane effects (stabilization or changes in trans-membrane gradients), influence on protein synthesis, influence on lipid metabolism by induction or inhibition of involved enzymes, or more general actions such as disturbances or damage of cellular membranes and cellular function. Some of these effects can easily be described as pharmacological actions, more or less independent of specific requirements in the chemical structure of the xenobiotics. Others are linked to specific chemical substituents such as carboxyl or alcoholic hydroxyl groups allowing the formation of lipid-xenobiotic conjugates and/or the channeling of xenobiotics into lipid metabolism. This review will give a short overview of the mechanisms of xenobiotic-influenced hepatic lipid and lipoprotein metabolism. PMID- 2257928 TI - Invasiveness of renal cell carcinoma--an in vitro model. AB - The invasive properties of human renal cell carcinoma were tested on a gel-like reconstituted basement membrane matrix extracted from Engelbreth-Holm-Swarm transplantable mouse tumor (Matrigel). Both high-grade (Fuhrmans's nuclear grade III) and low-grade (Fuhrman's nuclear grade I) renal carcinoma cells as well as normal human renal tubular cells were seeded onto a thin-layered, full-strength gel (1-2 mm). The normal tubular cells migrated to form small irregular colonies interconnected by polygonal networks of cell cords and grew along the surface contour of the gel. No evidence of distortion, dissolution, or invasion of underlying gel was observed but a thin layer of electron dense lamina was found to form underneath the cells. The noninvasive morphology was observed to have lasted for more than 3 weeks. On the contrary, both low-grade and high-grade carcinoma cells formed individual colonies and invaded the underlying matrix by developing invasion buds and subsequently cords or tubule-like structures of variable length. No basement-membrane-like electron dense deposit was observed at the cell-matrix interface. The observation that the mean invasion depth was higher in high nuclear grade carcinoma has significant implications on the association between invasiveness and nuclear grade. The findings that cancer cells closely contacted the surrounding matrix and reorganized the matrix in the immediate vicinity provided additional evidence of cell-matrix interaction. PMID- 2257929 TI - Light and electron microscopic observations on the cerebellum of guinea pigs following low-dose methotrexate. AB - The neurotoxicity of single and divided low-dose methotrexate (MTX) and the rescue effect of leucovorin (folic acid) were investigated by light and electron microscopic examination of the cerebellum of Guinea pigs. One group of animals received a single weekly intraperitoneal MTX in a dose of 10 mg/kg, a second received a similar dose divided into three equal fractions, and the third group received MTX rescued with an equal dose of leucovorin. The results showed degeneration of Purkinje cells indicated by shrinkage and distortion of perikarya, dissolution of mitochondrial cristae, and nuclear and nucleolar changes in all groups which received MTX. There was also astrocytic proliferation and perivascular edema. Lesser changes were found in the group which was rescued with leucovorin. The degenerative changes in the cerebellum particularly those of the Purkinje cells explain the neurological signs reported in cancer patients treated with MTX. PMID- 2257930 TI - Early atherogenesis in White Carneau pigeons: effect of a short-term regression diet. AB - The intracellular distribution of lipid shifts from cytoplasmic to lysosomal localization during the progression of atherosclerosis. It has been suggested that this shift may relate to regressability of lesions. The effects of reducing plasma cholesterol on the regression of early cholesterol-induced atherosclerosis were evaluated. Most small, early lesions disappeared after 5 weeks on the regression regimen. Larger lesions, however, did not change in extent even following 10 weeks regression. Although large lesions were not reduced in size under the regression conditions, total cytoplasmic lipid decreased. Paradoxically, the size of residual intracellular lipid deposits increased. The structural features of these remaining deposits suggest that they were lipid filled lysosomes. Leukocyte adherence to endothelium, which increases 10- to 20 fold during progression, returned to control levels over most areas of large lesions. Levels of adherent leukocytes remained elevated, however, over small lesions and at the edges of larger lesions. Our data indicate that regression is not a uniform process, but rather, even in early lesions, varies within separate intimal microdomains. In addition, our data suggest that part of the difference may reside in differential partitioning of lipid into lysosomes. PMID- 2257931 TI - The relation among vessel injury, thrombus formation, and platelet survival in rabbits. AB - Continuous or repeated injury of rabbit aortae by indwelling vascular catheters caused the deposition of platelets on the injured vessels and the formation of thrombi rich in platelets and fibrin at sites where flow was most disturbed and injury was most extensive. Incorporation of 51Cr platelets into the thrombi reached a maximum between 3 and 24 hr. The platelet-fibrin-rich thrombi remained reactive to circulating platelets for at least 14 days. Continuing reactivity of thrombi and the turnover of platelets in the thrombi were accompanied by an increase in the proportion of platelets that separated in the least dense fraction on Stractan density gradients. Platelet survival was also shortened (43.5 +/- 5.9 hr in animals with catheters, compared with 62.6 +/- 4.5 hr in animals with a sham operation), indicating that some platelets that had taken part in thrombus formation or had interacted with the injured vessel wall were rapidly cleared from the circulation. Platelets from rabbits that had had indwelling aortic catheters in place for 3 or 6 days survived significantly longer than those from animals with a sham operation upon injection of the platelets into normal animals; thus, continuous turnover of platelets on injured vessels and thrombi, and the clearance of altered platelets, leads to a population of younger platelets that survive longer. The continuing reactivity of thrombi may in part account for repeated occlusive episodes in vascular disease. The contribution of thrombin generation and fibrin formation to the platelet-rich thrombi is substantial and warrants the ongoing evaluation of treatment with a combination of anticoagulant and antiplatelet agents in arterial thrombosis and in thrombus formation on vascular catheters. PMID- 2257932 TI - Subcellular localization of HPA-23 in different rat organs: electron microprobe study. AB - The anti-viral drug HPA-23 (ammonium 21-tungsto-9-antimonate) has been proposed for use in the combat against AIDS. The two elements tungsten (W) and antimony (Sb) in the molecule enable the intracellular localization and possible breakdown of the product to be studied using electron probe microanalysis methods. Such studies have been carried out after intravenous injection of different doses of HPA-23 in the rat followed by removal of the liver, kidney, thymus, spleen, bone marrow, and lung. HPA-23 was concentrated in the lysosomes and localized in the macrophages of different tissues (thymus, spleen, and bone marrow). The W/Sb ratio was identical in these macrophages. This localization is perhaps relevant to the mechanism of action of HPA-23. PMID- 2257933 TI - Diploidization of bovine oocytes matured in vitro and parthenogenetically activated by electric shock. AB - Bovine in vitro matured oocytes were parthenogenetically activated by a single pulse of direct current. Suppression of second polar body extrusion by 60 V DC pulse followed by cytochalasin B treatment or 240 V DC-pulse were used to diploidize parthenogenones. Analysis of the cytological events 20 h postactivation clearly documented high efficiency of both diploidization techniques. All oocytes exposed to a single 60 V DC-pulse and then to cytochalasin B for 3 to 6 h were activated and 70% to 88% possessed two pronuclei. Exposure to 240-V DC-pulse for 10 and 20 microseconds activated all oocytes, 72% and 62% formed two pronuclei, but a high incidence (22% and 30%) of degenerated oocytes was observed. Prolonged in vitro culture of oocytes after parthenogenetic activation and diploidization treatment showed that formed pronuclei were able to fuse and single prometaphase to telophase mitotic cleavage figures developed in all oocytes fixed 28 h after activation, except one cytochalasin B-treated oocyte with two prometaphase sets of chromosomes. PMID- 2257934 TI - Cryopreservation of mouse 8-cell embryos in microdrops. AB - Eight-cell embryos collected from superovulated inbred strains and F1 hybrid mice were frozen by the microdrop technique developed in our laboratory. The technique based on pre-equilibration in medium with 10% glycerol, before transfer into vitrification solution, expel of embryos in 5 microliters to 20 microliters of vitrification solution directly into liquid nitrogen and thawing of microdrops in medium with 0.5 M sucrose was used. The behavior and morphological appearance of embryos during pre-freezing and post-thawing periods was documented. The efficiency of cryopreservation in microdrops was high, as documented by 90% to 100% of intact embryos after the freezing and thawing cycle. Furthermore, no zona pellucida damage was observed. The developmental potential of embryos frozen in microdrops was comparable with development of unfrozen embryos of the same genetic origin. After freezing and storage 83% to 93% of embryos developed to blastocysts and 73% to 92% embryos underwent "implantation" after 48 h and 96 h of in vitro culture, respectively. PMID- 2257935 TI - Construction of aggregation chimaeras from 8-cell mouse embryos stored for several years in liquid nitrogen. AB - Eight-cell embryos of 7 different inbred strains frozen and stored for 2 to 4 years in liquid nitrogen were used as the source of embryos and individual 1/8 blastomeres for construction of different types of aggregation chimaeras. Overall survival of stored embryos, evaluated by in vitro culture, ranged from 63% in A/By to 85% in C57BL/10By embryos. Chimaeric embryos prepared by aggregation of frozen/thawed zona-free 8-cell embryos continued in normal development through expanding blastocysts (77% to 93%) to in vitro implantations. Construction of directed chimaeras by total rebuilding of 8-cell embryos previously stored in liquid nitrogen was successful and resulted in normal development. Of the aggregates made by regular mixing of 1/8-blastomeres obtained from BALB/c and C57BL/6J embryos thawed from liquid nitrogen, 90% reached the blastocyst stage and 77% implanted after 48 h and 96 h of in vitro culture, respectively. Addition of 1/8 blastomeres from frozen/thawed BALB/c embryos to four 1/8-like blastomeres from nuclear transplantation experiments documented, as all of the 30 constructed aggregates formed expanding blastocysts within 48 h of in vitro culture, the possibility of using embryos from embryo banks for the rescue of products of genetic manipulations at the embryo level. PMID- 2257936 TI - Effects of five platinum complexes (cis-DDP, trans-DDP, CHIP IV, CBDCA, oxo-Pt) on the induction of sister chromatid exchanges (SCEs) and chromosomal aberrations in Vicia faba root-tip cells. AB - In a population of plant meristematic cells of Vicia faba the frequency of sister chromatid exchanges (SCEs), incidence of chromosomal aberrations and mitotic activity of cells was evaluated after short-term treatment (1 h) with antitumour active platinum complexes cis-DDP, CHIP IV, CBDCA, oxo-Pt and antitumour inactive trans-DDP. It was found that the action of platinum compounds in equimolar concentration 3.33 microM increases the level of SCEs 1.3 to 6.4-fold. The maximum effect in terms of SCE formation was observed after cis-DDP. Comparison of the incidence of SCEs and chromosomal aberrations in plant cells demonstrated that the tested drugs had a greater effect on SCE formation than on chromosomal aberration induction. Inhibition of mitotic activity correlated with the total cytogenetic damage to chromosomes of Vicia faba cells. PMID- 2257937 TI - Relationship between internalization kinetics and cytotoxicity of mistletoe lectin I to L1210 leukaemia cells. AB - We have taken two different approaches to the study of the entry of mistletoe lectin I (MLI) into murine L1210 leukaemia cells. As detected by cellular protein synthesis and DNA synthesis inhibition, the lectin was cytotoxic to L1210 leukaemia cells. Inhibition of [3H]leucine and [3H]thymidine incorporation into L1210 cells by MLI was found dose dependent in a concentration range from 10(-16) to 10(-12) mol/ml. The kinetics of cellular protein synthesis inhibition by MLI was concentration dependent, too. Using preembedding electron microscopy, the binding and intracellular routing of the gold-labelled lectin (MLI.Au15) were studied. MLI was internalized into L1210 leukaemia cells by two different pathways: via coated pits to coated vesicles and via long enclosed invaginations of the plasma membrane. PMID- 2257938 TI - Age dependence of the number of the fibroblasts (CFUf) and haemopoietic stem cells (CFUs) in bone marrow and spleen of rats. AB - During maturation of rats the progenitor cells of fibroblasts (CFUf) increase in number in bone marrow, whereas they decrease in spleen. The numbers of the haemopoietic stem cells (CFUs) also exhibit similar changes. PMID- 2257939 TI - Decrease in the number of progenitors of fibroblasts (CFUf) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 biosatellite. AB - A decrease in the number of progenitors of fibroblasts (CFUf) was found in bone marrow of rats that underwent a 14-day flight in the state of weightlessness onboard the Cosmos-2044 biosatellite, immediately after flight, when compared with rats maintained in control conditions of terrestrial gravitation. These changes may be explained by the action of specific factors of microgravitation. PMID- 2257940 TI - Effect of 13-cis-retinoic acid treatment on protein kinase C from 10T1/2 cells. AB - Protein kinase C from 10T1/2 cells can be eluted by linear gradient of NaCl in two fractions. Following treatment with 10(-5) M 13-cis-retinoic acid a decrease of total PKC activity was observed, mainly at the expense of the 150 mM NaCl eluted fraction. PMID- 2257941 TI - [Regulation of peptide hydrolase activity in psoriasis]. AB - Clinico-biological examination of 154 patients with psoriasis resulted in data showing high activity of endo- and exopeptidases in efflorescences of that dermatosis. This was accompanied by depressed activity of trypsin inhibitor. At the same time magnesium deficiency, polysaccharide decrease and leucocyte increase were stated to be in the focus of skin damage. That character of interrelation, which play an important role in the pathogenesis of this widespread skin disease, is demonstrated. PMID- 2257942 TI - [Stability of metronidazole, prednisolone and dexamethasone in urea-containing Elacutan W dermatologic agent]. AB - Metronidazole was investigated in the basic dermatologic agent Elacutan W to improve the topical therapy of rosacea. The suitability of that basic dermatologic agent was verified for metronidazole, prednisolone and dexamethasone by stability tests (UV-spectroscopy, pH) and by in-vitro-liberation-measurements (membrane method). The drugs are stable for a period of 100 days. PMID- 2257944 TI - [Copper allergy--a rare form of sensitization]. AB - It is reported on a 41 years old man who suffered from dermatitis by contact with technical carbon and graphite products. In patch testing we found positive reactions to colophony, metallic copper and copper sulfate. By avoidance, of noxae the patient was free of symptoms. PMID- 2257943 TI - [Promotion of hair growth with thiocyanate in guinea pigs]. AB - The advancement of growth of albino guinea pig hair has been induced by sodium thiocyanate through oral application (32 mg/kg) and more distinctly through balneological use (0.3, 5 resp. 10 g/l). The density of the hair has been increased at 6-38%, the longitudinal growth advanced at 2-14% and the phases of follicle cycle have been changed on behalf of anagenic hair at 11-39%. PMID- 2257945 TI - [INPRET (INformation on PREdictive Tests). A data bank on the allergenic potential of industrial and environmental agents]. PMID- 2257946 TI - Genetic mapping and physical characterization of parvalbumin genes. PMID- 2257947 TI - Expression of cloned genes and translation of messenger RNA in microinjected Xenopus oocytes. PMID- 2257948 TI - Non-receptor protein tyrosine kinases of normal tissues. PMID- 2257949 TI - Action of inhibitors on brain glutamate decarboxylase. PMID- 2257950 TI - Comparison of the properties of purified mitochondrial and cytosolic rat kidney transamidinase. AB - 1. Mitochondrial rat kidney transamidinase was solubilized by two extractions with the surfactant Zwittergent 3-14. 2. Mitochondrial and cytosolic forms of rat kidney transamidinase were purified by chromatography on DEAE-Trisacryl M, phenyl Sepharose Cl-4B and hydroxylapatite columns. 3. The specific activity of purified mitochondrial enzyme was significantly higher than purified cytosolic enzyme. 4. The subunit molecular mass, the electrophoretic mobility under nondenaturing conditions, and the activation energy were similar for purified mitochondrial and cytosolic transamidinase. PMID- 2257951 TI - Changes in cerebral free fatty acids and triacylglycerols in focal cerebral ischemia. AB - 1. Focal cerebral ischemia was induced in anesthetized rats by occluding the stem of the proximal middle cerebral artery. 2. The levels of free fatty acids, such as stearic and arachidonic acids, in the ischemic cerebral cortex increased progressively until 60 min after occlusion, but thereafter they decreased rapidly. 3. In contrast to the time-dependent changes in free fatty acids, the levels of triacylglycerol (TAG) in the ischemic cerebral cortex continued to increase for 120 min after occlusion. Increases in TAG-palmitate, -stearate and arachidonate accounted for the increase in the triacylglycerol level. 4. The pattern of the lipid changes in focal cerebral ischemia differs from those reported in bilateral diffuse cerebral ischemia induced by arterial occlusion or in decapitation ischemia. PMID- 2257952 TI - Soluble "high Km" 5'-nucleotidase activity in human T- and B-lymphoblasts: isolation and some properties. AB - 1. Activity of "high Km" 5'-nucleotidase was investigated in the soluble fractions from cultured human T- and B-lymphoblasts. 2. Using gel filtration chromatography and 5'-AMP-Sepharose 4B affinity chromatography, it separated high Km 5'-nucleotidases from other two different soluble nucleoside 5' phosphomonoesterase activities. 3. The molecular mass of the high Km enzymes from T- and B-lymphoblasts were 210 and 200 kDa, respectively. The optimum pH was at 6.5, and the Km values for IMP and AMP were 0.4 and 0.9 mM, respectively. 4. These properties of high Km 5'-nucleotidases were similar to those previously described from different tissues. These data indicate that soluble high Km 5' nucleotidase coexists with "low Km" enzyme. PMID- 2257953 TI - Activity measurement of lysosomal cysteine proteinases, cathepsins B, H and L, in crude tissue extracts, and their relation to the fractional rate of protein degradation. AB - 1. The fractional rate of protein degradation was measured in vivo and compared with the lysosomal enzyme activities of several rat tissues. Good agreement was observed between them. 2. A specific method for determining lysosomal cysteine dependent cathepsins, B, L and H, was demonstrated. PMID- 2257954 TI - Depressed gluconeogenesis and ureogenesis in isolated hepatocytes after intermittent hypoxia in rats. AB - 1. Rats were exposed to hypobaric hypoxia (equivalent altitude 4500 m), 2 x 2 hr per day, for 5 days. Isolated hepatocytes were prepared on day 6 after 18 hr of fast and also from control normoxic animals. The hepatocytes were incubated (120 min) with various substrates. 2. ATP contents were lower in hepatocytes from exposed as compared to control animals whether at the beginning (14%) or at the end (-6 to -33%) of incubation depending on the substrate. 3. Gluconeogenesis from all precursors (lactate, alanine, pyruvate, glutamine) was significantly reduced (40-50%) in exposed as compared to control animals. 4. Ureogenesis from alanine and from pyruvate + NH4Cl was also markedly depressed in exposed animals but no differences were noticed with glutamine or lactate + NH4Cl and alanine + NH4Cl. 5. Results are discussed in relation to known effects of acute and chronic hypoxia, interrelationship between gluconeogenesis and ureogenesis, taking into account the inhomogeneity of liver and the metabolic properties of periportal and perivenous hepatocytes. PMID- 2257955 TI - Separation and biochemical characterization of blood group N antigen precursor glycoproteins with Thomsen-Friedenreich (T) activity, T-active glycoproteins and N antigen precursor glycoproteins from ascites of primary ovarian cancer patients. AB - 1. Three perchloric acid-soluble fractions from ascites of three primary ovarian cancer patients were subjected to Sephacryl S-300 gel filtration, respectively, and three Fr. 1 which were eluted in the vicinity of void volume as minor fractions, were then separated by a systematic affinity chromatography using Vicia unijuga lectin-Sepharose CL-4B column and Arachis hypogaea lectin-Sepharose CL-4B column into three glycoproteins, blood group N antigen precursor glycoprotein with Thomsen-Friedenreich (T) activity, T-active glycoprotein and N antigen precursor glycoprotein, respectively. 2. These nine glycoproteins separated in yields of 0.1-1.3 mg per 100 ml of ascites, were demonstrated to be mucin-type glycoproteins with Mw of 1,791,000-4,921,000 and contained 33.8-56.1% carbohydrates. PMID- 2257956 TI - Translocation of intestinal alkaline phosphatase in streptozotocin-induced diabetic rats. AB - 1. We determined the organ of origin and possible mechanism of translocation into the circulation of alkaline phosphatase (ALPase) in the diabetic rat. 2. Experimental diabetes was induced by injection of streptozotocin, resulting in a 8.2-fold elevation in serum ALPase activity. In this case, the major ALPase isozyme detected in serum was intestinal ALPase. 3. In in vitro experimental systems, ALPase was readily released from the duodenal plasma membrane by bacterial phosphatidylinositol-specific-phospholipase C (PI-PLase C) but little if any was released from the ileal membrane. 4. Serum and ileal ALPases were identical in terms of molecular size, whereas duodenal ALPase clearly differed from the serum enzyme. 5. Based on an investigation of the sugar moiety, more of the fraction having higher concanavalin A affinity was found in serum ALPase than with in the case of either of the intestinal ALPases. Serum and intestinal ALPases also differed slightly regarding isoelectric points. 6. Consequently, these data suggest that the serum ALPase of the diabetic rat is derived from ileal ALPase, and it is unlikely that the appearance of ALPase in the circulation is simply the result of solubilization by the action of PI-PLase C or phospholipase D. PMID- 2257957 TI - Combined ranitidine and pirenzepine in the treatment of duodenal ulcer: a multicentre double-blind study using endoscopy. AB - The efficacy of a combination of ranitidine and pirenzepine in the short-term treatment of duodenal ulcer was evaluated in a double-blind trial. In a multicentre study, 352 patients with active duodenal ulcers were randomly allocated to be treated with 300 mg/day ranitidine plus placebo (group I), 300 mg/day ranitidine plus 50 mg/day pirenzepine (group II), or 300 mg/day ranitidine plus 100 mg/day pirenzepine (group III) for 4 weeks. The respective healing rates assessed using endoscopic examination after 2 and 4 weeks' treatment were 40% and 70% in group 1, 44% and 82% in group II, and 37% and 77% in group III. The differences between the treatment groups were not significant, although 300 mg/day ranitidine plus 50 mg/day pirenzepine tended to be superior to the other treatments. Analgesic activity was the same in the three groups with 33%, 34% and 33% reductions, respectively, in the numbers of patients experiencing pain after 2 weeks. Side-effects (mainly dry mouth and blurred vision) were significantly more frequent in group III patients. PMID- 2257958 TI - The efficacy of bismuth subsalicylate in relieving gastro-intestinal discomfort following excessive alcohol and food intake. AB - The safety and efficacy of bismuth subsalicylate in relieving the symptoms of gastro-intestinal distress due to excess ingestion of food and drink were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study. Of the 132 healthy adult volunteers who were encouraged to overindulge in food and drink during a simulated cocktail/dinner party, 91 (68.9%) experienced symptoms of gastric distress and of these 43 were randomly assigned to receive bismuth subsalicylate and 48 placebo. Subjects took the formulation as needed every 30-60 min, with a maximum of eight doses during the 24-h study period. Subjects who received bismuth subsalicylate had significantly superior relief (P less than 0.01) of the individual symptoms of nausea, sense of fullness, heartburn, eructation, stomach pain and flatulence, as well as superior overall relief (P less than 0.02). The time between the first doses of medication and the attainment of good or excellent relief was also significantly shorter (P less than 0.01) in the bismuth subsalicylate-treated subjects for the individual symptoms of nausea, sense of fullness, heartburn and eructation. There were no adverse reactions. PMID- 2257959 TI - Percutaneous treatment of acute soft tissue lesions with naproxen gel and ketoprofen gel. AB - A randomized independent-group, single-blind study was performed to compare the analgesic efficacy and the local and cosmetic tolerability of 3-5 cm of 10% naproxen gel with 10% ketoprofen gel in 30 patients complaining of moderate or severe pain due to acute soft tissue lesions. Both drugs were administered topically and were applied to the painful area at least once every 12 h as required. Naproxen gel was effective, cosmetically acceptable and safe in the treatment of acute soft tissue lesions. Efficacy and tolerability of both naproxen gel and ketoprofen gel were comparable, although naproxen gel produced a significantly greater reduction in pain on deep palpation by the third day of treatment. PMID- 2257960 TI - Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. AB - The efficacy and tolerability of Serratia peptidase were evaluated in a multicentre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7-8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7-8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflammatory, anti-oedemic and fibrinolytic activity and acts rapidly on localized inflammation. PMID- 2257961 TI - A comparison of butoconazole nitrate cream with econazole nitrate cream for the treatment of vulvovaginal candidiasis. AB - In a randomized, single-blind, parallel study the safety and efficacy of 2% butoconazole nitrate cream used for 3 days were compared with those of 1% econazole nitrate cream used for 7 days at night in patients with vulvovaginal candidiasis. Patients in both treatment groups had positive potassium hydroxide smears and fungal cultures, and were similar in age, disease duration and history, obstetric history and contraceptive use. Of the 75 patients enrolled, 63 with a Candida albicans infection were included in the efficacy analyses. Evaluations were made at the start of the study (visit 1), after 10-23 days (visit 2) and after 24-45 days (visit 3). Both drugs significantly reduced all signs and symptoms, and at visits 2 and 3 the percentages of patients considered microbiologically, clinically and therapeutically cured were consistently higher for butoconazole- than for econazole-treated patients, although differences were not statistically different. Although both drugs were safe and well tolerated, it is concluded that butoconazole because of its much shorter regimen and superior clinical and microbiological performance was the drug of choice. PMID- 2257962 TI - Effects of calcium, magnesium, tobramycin and theophylline on phenobarbitone binding to serum proteins. AB - Binding of phenobarbitone to human serum proteins was determined in vitro using ultrafiltration. At therapeutic concentrations of 10-600 microM, 63.51 +/- 2.5% of the phenobarbitone was bound to total serum proteins. The binding kinetics were non-saturable and the plasma apparent affinity coefficient (NKa) was 0.791 +/- 0.09 for normal serum and 0.664 +/- 0.06 for chromatographed serum. Tobramycin and theophylline at therapeutic concentrations of 10 and 15 micrograms/ml, respectively, reduced NKa compared with the values found in normal serum. Calcium and especially magnesium at physiological concentrations of 2.5 and 5 mM, respectively, increased NKa compared with values obtained in chromatographed serum, whereas at supraphysiological concentrations of magnesium of 15 mM NKa was reduced. It is concluded that free phenobarbitone concentrations in serum can be modified by calcium, magnesium, tobramycin and theophylline, and this fact must be considered when studying enzyme induction and other properties of phenobarbitone. PMID- 2257963 TI - Effects of ibudilast on calcium deposition in soft tissues of rabbits with atherosclerosis. AB - The effects of 2.5 mg/kg.day ibudilast, with or without 300 mg/kg.day nicomol, or 10 mg/kg.day ibudilast on calcium and magnesium concentrations in the central nervous system (CNS), heart, liver, kidney, skeletal muscle, abdominal aorta and bone were determined in rabbits fed a 1% cholesterol-rich diet for 3 months. Serum thromboxane B2 concentrations were reduced in rabbits treated with 10 mg/kg.day ibudilast or with 2.5 mg/kg.day ibudilast plus 300 mg/kg.day nicomol, and atherosclerotic lesions were ameliorated compared with untreated rabbits. Calcium concentrations in the frontal cortex and cerebellum were lower in ibudilast/nicomol-treated rabbits and in those fed a standard diet compared with those receiving a cholesterol-rich diet only. Calcium concentrations in the pons and abdominal aorta were also lower in ibudilast/nicomol-treated rabbits whereas the calcium concentrations in the cerebellum were lower in rabbits treated with either 2.5 or 20 mg/kg.day ibudilast. There were no significant changes in tissue magnesium concentrations after feeding a cholesterol-rich diet, with or without drug treatment. It is concluded that 2.5 mg/kg.day ibudilast plus 300 mg/kg.day nicomol or 10 mg/kg.day ibudilast produced a scavenger effect on calcium deposited in the CNS and abdominal aorta of rabbits fed a cholesterol-rich diet. PMID- 2257964 TI - A comparative clinical trial of duodenal ulcer healing with two regimens of cimetidine: 800 mg once nightly and 400 mg twice daily. AB - The efficacy and safety of two dosage regimens of cimetidine were compared in a single-blind study of 50 adults with endoscopically proven duodenal ulcers. Patients were randomly allocated to receive 800 mg cimetidine taken once nightly or 400 mg cimetidine taken twice daily for 4 weeks. Following 4 weeks' treatment patients again underwent endoscopy and, if healing was incomplete, they received a further 4 weeks' treatment. At 4 weeks, healing occurred in 21/25 (84%) patients on the once-daily regimen and in 15/25 (60%) patients treated twice daily (P less than 0.05). Cumulative healing rates after 8 weeks' treatment were 92% and 96%, respectively. Symptomatic improvement was obtained to the same degree with both regimens. No adverse effects were recorded and laboratory values remained normal during both treatments. The results indicate that cimetidine given as one dose each night was superior to the twice-daily regimen. PMID- 2257965 TI - Investigation of the effect of ketotifen on alcohol-induced asthma: a case study. AB - A male patient with bronchial asthma suffered severe exacerbation of symptoms after drinking alcohol and this was not prevented by treatment with bronchodilators. After taking 1 mg ketotifen twice daily for nasal obstruction, within 1 month there was no longer any exacerbation of symptoms by alcohol. Blood samples were taken and peripheral eosinophils were purified and incubated with beer antigen. Using a chemiluminescence method, it was shown that pretreatment with ketotifen dose dependently inhibited the generation of the highly reactive oxygen metabolite superoxide (O2-) by the eosinophils. It is proposed that ketotifen prevented the alcohol-exacerbated asthma attacks by inhibiting the release of tissue-damaging superoxide from eosinophils. PMID- 2257966 TI - Differentiation of a calsequestrin-containing endoplasmic reticulum during sea urchin oogenesis. AB - We have used light and electron microscopic immunolocalization to study the distribution of a sea urchin calsequestrin-like protein (SCS) during sea urchin oogenesis. SCS was localized exclusively in the lumen of the endoplasmic reticulum (ER) and in the nuclear envelope of oocytes of all maturation stages. Immunoelectron microscopy also revealed that SCS is not present in golgi complexes of oocytes. Double label immunofluorescent staining of frozen sections of ovary with the SCS antiserum and an antibody to the cortical granule protein hyalin indicated a dramatic morphogenesis of the SCS-containing ER (SCS-ER) coincident with oocyte maturation. This differentiation included an apparent increase in the amount and complexity of the cytoplasmic SCS-ER network, the transient appearance of stacks of SCS-ER cisternae in synthetically active vitellogenic oocytes, and the restructuring of the SCS-ER in the cortex. Immunofluorescence of isolated oocyte cortices showed a plasma membrane associated SCS-ER which was much less dense and regular than that found surrounding the cortical granules in the mature unfertilized egg cortex. Cytoplasmic and cortical microtubule arrays are present in oocytes and may provide the basis for the SCS-ER distributional dynamics. The results of this study underscore the dynamic nature of ER and how it's organization reflects cellular functions. We suggest that the establishment during oogenesis of the dense SCS-ER tubuloreticulum provides the egg with the calcium sequestration and release apparatus that regulates calcium fluxes during egg activation and early development. PMID- 2257967 TI - Regulation of contractile protein gene family mRNA pool sizes during myogenesis. AB - During myogenesis, muscle contractile protein gene expression is induced and the products are used to assemble the contractile apparatus characteristic of striated muscle. The different muscle proteins are accumulated in a fixed stoichiometric ratio related to their organization in the contractile apparatus. We have examined the relationship between contractile protein gene expression and the maintenance of stoichiometry at different stages of human myogenesis. Essentially all of the known components of adult human skeletal muscle thick and thin filaments have been cloned in the form of cDNAs and used to generate isoform specific DNA probes. The expression of fast, slow, and cardiac isoforms was measured in human myogenic primary culture and in fetal and adult human skeletal muscle. We observed that neither fast nor slow nor cardiac isoforms are coordinately regulated at the level of comparative transcript accumulation throughout myogenesis. Thus, the stoichiometry of contractile protein levels cannot be explained by coordination of expression in each of these isoform classes. However, we find that the stoichiometry of mRNA accumulation of each gene family is very similar among three developmental stages: myotubes, fetal skeletal muscle, and adult skeletal muscle. This is consistent with the possibility that the maintenance of stoichiometry between the contractile proteins could be largely regulated by the total accumulation of mRNA from each of these gene families. PMID- 2257968 TI - Cell migration in the formation of the pronephric duct in Xenopus laevis. AB - To determine if cell migration is involved in the formation of the pronephric duct in Xenopus, we used morphometry, ablation, and videomicroscopy of vitally stained cells to study duct formation. In St 23-24 (Nieuwkoop and Faber, 1956) embryos, a ridge of cells forms caudal to the pronephric rudiment. The ridge lengthens at approximately the same rate as the embryonic trunk from St 23 to St 31. Ablation experiments demonstrated that the ridge constitutes the pronephric duct rudiment (PDR); when the ridge was ablated at St 23-24, little or no duct formation occurred, whereas a duct formed when the pronephric rudiment was ablated and the ridge left intact. Vital dye injections showed that the PDR forms from the intermediate mesoderm ventral to myotomes IV-VIII. From St 29/30 to St 33/34, the PDR actively elongates along the ventral edge of the myotomes as far as myotome XIV, where it joins the cloaca as the pronephric duct. Videomicroscopy of vitally stained cells showed that the PDR elongates throughout its length and does not incorporate additional cells from the mesoderm over which it elongates. The results strengthen the case for a common mode of pronephric duct formation among amphibian species. PMID- 2257969 TI - Control of sperm nuclear behavior in physiologically polyspermic newt eggs: possible involvement of MPF. AB - We have studied the mechanism controlling the behavior of accessory sperm nuclei in physiologically polyspermic eggs of the newt, Cynops pyrrhogaster. Our approach was to identify cytoplasmic components which would prevent the usual degeneration of accessory sperm nuclei. Injection of cytoplasm from unfertilized eggs, but not fertilized ones, induced multipolar cleavage in polyspermically fertilized eggs as well as centrosome separation and formation of extra bipolar spindles in accessory sperm nuclei. Cytosols extracted from unfertilized Cynops or Xenopus eggs also were active in inducing multipolar cleavage, as were germinal vesicle materials from oocytes of the frogs Xenopus or Rana or of Cynops. In all of these cases, the nuclear cycle as well as the onset of first cleavage was delayed relative to those in control eggs. In contrast, injection of an extract with maturation-promoting factor (MPF) activity, prepared from unfertilized Xenopus eggs, induced precocious and multipolar cleavage when injected into fertilized Cynops eggs. Injection of the MPF-containing extract caused acceleration of the nuclear cycle as well as formation of extra bipolar spindles by the accessory sperm nuclei. These results suggest that a local deficiency of MPF may lead to the degeneration of accessory sperm nuclei in physiologically polyspermic eggs. PMID- 2257970 TI - Continuously growing bipotential and monopotential myogenic, adipogenic, and chondrogenic subclones isolated from the multipotential RCJ 3.1 clonal cell line. AB - The clonal multipotential RCJ 3.1 cell line, which gives rise to myotubes, adipocytes, chondrocytes, and osteoblasts, contains different progenitor subpopulations. By limiting dilution analysis, of 296 single colonies identified, approximately 20% contained a single recognizable cell type, approximately 10% contained two cell types, and approximately 1% contained three cell types. We recloned RCJ 3.1 and isolated continuously growing subclones, including four novel bipotential (adipocytes/chondrocytes; adipocytes/myotubes and chondrocytes/myotubes) cell populations, whose phenotypes bred true. In the bipotential subclones, single colony analyses confirmed the presence of single cells which could both self-renew the bipotential progenitors and give rise to their respective committed monopotential lineages. Eight subclones were restricted to a single cell lineage and were considered monopotential; one of these is a novel cell line differentiating into cartilage. Thus, we have isolated unique monopotential and bipotential progenitor cell lines which provide a valuable model for studying the mechanisms leading to lineage restriction in mesenchymal populations. PMID- 2257971 TI - The effect of ions, ion channel blockers, and ionophores on uptake of vitellogenin into cockroach follicles. AB - Since calcium plays an important role in vitellogenin binding and uptake in Nauphoeta cinerea and because calcium channels have been described in follicles of this species, we investigated the effect of various ions, ionophores, and ion channel blockers on vitellogenin uptake in vitro. Calcium significantly stimulated vitellogenin uptake; this effect could be substituted best by barium and less well by strontium and magnesium. The stimulatory effect of calcium, and to a certain extent also that of barium, was dependent on the vitellogenin concentration, whereas the effect of strontium and magnesium was not. In the presence of calcium, vitellogenin uptake was inhibited by barium, strontium, and magnesium as well as by the transition elements nickel, cobalt, and zinc, but not by manganese which had a stimulatory effect. Valinomycin, verapamil, tetraethylammonium, and atropine reduced vitellogenin uptake, while amiloride and ouabain were ineffective. Our results indicate that calcium inward (and possibly potassium outward) fluxes play an important role in vitellogenin uptake. PMID- 2257972 TI - Cell cycle length, cell size, and proliferation rate in hydra stem cells. AB - We have analyzed the cell cycle parameters of interstitial cells in Hydra oligactis. Three subpopulations of cells with short, medium, and long cell cycles were identified. Short-cycle cells are stem cells; medium-cycle cells are precursors to nematocyte differentiation; long-cycle cells are precursors to gamete differentiation. We have also determined the effect of different cell densities on the population doubling time, cell cycle length, and cell size of interstitial cells. Our results indicate that decreasing the interstitial cell density from 0.35 to 0.1 interstitial cells/epithelial cell (1) shortens the population doubling time from 4 to 1.8 days, (2) increases the [3H]thymidine labeling index from 0.5 to 0.75 and shifts the nuclear DNA distribution from G2 to S phase cells, and (3) decreases the length of G2 in stem cells from 6 to 3 hr. The shortened cell cycle is correlated with a significant decrease in the size of interstitial stem cells. Coincident with the shortened cell cycle and increased growth rate there is an increase in stem cell self-renewal and a decrease in stem cell differentiation. PMID- 2257973 TI - Putative intermediates in the nerve cell differentiation pathway in hydra have properties of multipotent stem cells. AB - We have investigated the properties of nerve cell precursors in hydra by analyzing the differentiation and proliferation capacity of interstitial cells in the peduncle of Hydra oligactis, which is a region of active nerve cell differentiation. Our results indicate that about 50% of the interstitial cells in the peduncle can grow rapidly and also give rise to nematocyte precursors when transplanted into a gastric environment. If these cells were committed nerve cell precursors, one would not expect them to differentiate into nematocytes nor to proliferate apparently without limit. Therefore we conclude that cycling interstitial cells in peduncles are not intermediates in the nerve cell differentiation pathway but are stem cells. The remaining interstitial cells in the peduncle are in G1 and have the properties of committed nerve cell precursors (Holstein and David, 1986). Thus, the interstitial cell population in the peduncle contains both stem cells and noncycling nerve precursors. The presence of stem cells in this region makes it likely that these cells are the immediate targets of signals which give rise to nerve cells. PMID- 2257974 TI - Expression of growth factors during the differentiation of embryonic stem cells in monolayer. AB - Embryonic stem (ES) cells, derived in culture directly from the inner cells mass (ICM) of blastocysts, more closely resemble their embryonic counterparts than the more commonly used embryonal carcinoma (EC) cells derived from teratocarcinomas. In view of the potential role of growth factors in early development, we have now followed changes in the expression of transforming growth factor beta (in particular TGF beta 1, beta 3, beta 4), platelet-derived growth factor (PDGF-A, PDGF-B) and insulin-like growth factor (IGF II) during the differentiation of ES cells in monolayer. When maintained in medium conditioned by Buffalo rat liver cells (BRL-CM) to inhibit differentiation, ES cells expressed 2.5 and 1.8 kb transcripts for TGF beta 1, as well as transcripts for TGF beta 4, PDGF-A, and low levels of PDGF-B, but not TGF beta 3 or IGF II. After formation of parietal endoderm-like cells by addition of retinoic acid (RA) to BRL-CM, the 1.8-kb transcript of TGF beta 1 and PDGF-A expression were reduced, IGF II mRNA and a single TGF beta 3 transcript of 3.8 kb were induced while PDGF-B and TGF beta 4 remained virtually unchanged. By contrast, in ES cells induced to differentiate by the absence of BRL-CM, unusual transcripts for TGF beta 3 of 3.0 and 6.0 kb became detectable and PDGF-B expression increased. The changes in growth factor expression in ES cells are compared with those in F9 and P19 EC cells induced to differentiate in monolayer by RA. PMID- 2257975 TI - Genomic organization and polypeptide primary structure of zona pellucida glycoprotein hZP3, the hamster sperm receptor. AB - During the course of fertilization in mammals, free-swimming sperm bind tightly to receptors located in the egg extracellular coat, or zona pellucida. Recently, the hamster sperm receptor, a 56,000 Mr zona pellucida glycoprotein called hZP3, was identified and partially characterized (C. C. Moller et al., (1990). Dev. Biol. 137, 276-286). Here, we describe genomic cloning of hZP3, certain organizational features of the hZP3 gene, and primary structures of hZP3 mRNA and polypeptide. The findings are compared with reported results of comparable analyses of the mouse sperm receptor, an 83,000 Mr zona pellucida glycoprotein called mZP3. Such comparisons reveal a high degree of conservation of genomic organization and polypeptide structure for the two mammalian sperm receptors, despite the considerable difference in their Mrs. These findings are of interest in view of the extremely restricted expression of the ZP3 gene during development and the important role of ZP3 oligosaccharides in gamete adhesion. PMID- 2257976 TI - Spatial distribution of the capacity to initiate a secondary embryo in the 32 cell embryo of Xenopus laevis. AB - To examine the spatial distribution of dorsal determinants in the early embryos of Xenopus laevis, individual cells from the 32-cell embryo were transplanted into the same tier of the ventral side of a synchronous recipient. Their abilities to initiate a secondary embryo were measured by the incidence of secondary embryos and by the length of the secondary axis relative to the primary embryo. The ability was found to be localized in all cells (A1, B1, C1, and D1) of the dorsal most column and in the vegetal cells (C2 and D2) of the dorsolateral column. Transplanted C1 (subequatorial) cells caused the highest incidence of a secondary embryo and the average relative length of the secondary embryo was also greatest. Effectiveness decreased in the order: D1, B1, D2, C2, and A1. When these results were compared with Dale and Slack's fate map of the 32 cell embryo, it was concluded that the distribution of dorsal determinants is unique and does not coincide with the prospective regions for any tissues, though it is somewhat similar to the prospective region of dorsal endoderm or notochord. From these results it seems that dorsal determinants do not determine a particular tissue in an embryo but rather the "dorsal" region of an embryo. PMID- 2257977 TI - Subcellular localization of sea urchin egg spectrin: evidence for assembly of the membrane-skeleton on unique classes of vesicles in eggs and embryos. AB - A recent study from our laboratory on the sea urchin egg suggested that spectrin was not solely restricted to the plasma membrane, but instead had a more widespread distribution on the surface of a variety of membranous inclusions. (E. M. Bonder et al., 1989, Dev. Biol. 134, 327-341). In this report we extend our initial findings and provide experimental and ultrastructural evidence for the presence of spectrin on three distinct classes of cytoplasmic vesicles. Immunoblot analysis of membrane fractions prepared from egg homogenates establishes that spectrin coisolates with vesicle-enriched fractions, while indirect immunofluorescence microscopy on cryosections of centrifugally stratified eggs demonstrates that spectrin specifically associates with cortical granules, acidic vesicles, and yolk platelets in vivo. Immunogold ultrastructural localization of spectrin on cortices isolated from eggs and early embryos details the striking distribution of spectrin on the cytoplasmic surface of the plasma membrane and the membranes of cortical granules, acidic vesicles, and yolk platelets, while quantitative studies show that relatively equivalent amounts of spectrin are present on the different membrane surfaces both before and after fertilization. These data, in combination with the localization of numerous spectrin crosslinks between actin filaments in surface microvilli, suggest that spectrin plays a pivotal role in structuring the cortical membrane-cytoskeletal complex of the egg and the embryo. PMID- 2257978 TI - Sea urchin spectrin in oogenesis and embryogenesis: a multifunctional integrator of membrane-cytoskeletal interactions. AB - Using indirect immunofluorescence microscopy on semithin cryosections of maturing ovarian tissue, eggs, and developing embryos, we have mapped the cellular distribution and dynamic redistribution of spectrin in oogenesis and early embryogenesis. During oogenesis, spectrin is initially found in the cortex of oogonia and previtellogenic oocytes, and later accumulates in the cytoplasm of vitellogenic oocytes on the surfaces of cortical granules, pigment granules/acidic vesicles, and yolk platelets. Following egg activation, spectrin undergoes a rapid redistribution coincident with three major developmental events including: (1) restructuring of the cell surface, (2) translocation of pigment granules/acidic vesicles to the cortex during the first cell cycle, and (3) amplification of the embryo's surface during the rapid cleavage phase of early embryogenesis. The synthesis and storage of spectrin during oogenesis appears to prime the egg with a preestablished pool of membrane-cytoskeletal precursor for use during embryogenesis. Results from this study support the hypothesis that spectrin may function as a key integrator and modulator of multiple membrane cytoskeletal functions during embryonic growth and cellular differentiation. PMID- 2257979 TI - Synthesis of two Drosophila male accessory gland proteins and their fate after transfer to the female during mating. AB - The male accessory gland of Drosophila is an adult secretory tissue which contributes many products to the male ejaculatory fluid. The secretions of the accessory gland affect the behavior and physiology of the female fly after mating, reducing her receptivity to courtship and stimulating egg production and oviposition. We have examined the developmental and mating-stimulated expression of two accessory gland proteins in the male and their transfer to and fates in the mated female. One of these proteins, msP 355a, has features of a prohormone and contains a region with amino acid sequence similarity to the egg-laying hormone of Aplysia; the other, msP 355b, is a small acidic protein. Both proteins are first detected in the accessory gland only after eclosion, although their transcripts are already present in late pupae. Both proteins are initially detected in the two morphologically distinct secretory cell types of the accessory gland, the main cells, and the secondary cells. In the glands of aged virgin males, they are only detected in the large vesicles of the secondary cells and in the lumen of the gland. Copulation results in an increase in the mRNAs for both proteins, as well as renewed translation of the proteins at least in the main cells. Both proteins are transferred to the female genital tract during copulation, and rapidly enter the female hemolymph. msP 355a is subject to rapid and specific cleavage within the female genital tract, but not in the hemolymph; msP 355b is not cleaved in either the female genital tract or the hemolymph. PMID- 2257980 TI - The critical period for peripheral specification of dorsal root ganglion neurons is related to the period of sensory neurogenesis. AB - Thoracic sensory neurons in bullfrog tadpoles can be induced to form connections typical of brachial sensory neurons by transplanting thoracic ganglia to the branchial level at stages when some thoracic sensory neurons already have formed connections. In order to find out how many postmitotic sensory neurons survive transplantation, [3H]thymidine was administered to tadpoles in which thoracic ganglia were transplanted to the brachial level unilaterally at stages VII to IX. Between 16 and 37% of the neurons in transplanted ganglia were unlabeled, as compared to 46 to 60% in unoperated ganglia. Transplanted ganglia contained fewer unlabeled neurons than corresponding unoperated ganglia, indicating that transplantation caused degeneration of postmitotic neurons. Therefore, a large fraction of the neurons that formed connections typical of brachial sensory neurons probably differentiated while they were at the brachial level. PMID- 2257982 TI - Puzzles about epilepsy. PMID- 2257981 TI - Counterproductive transcriptional and translational regulation of elongation factor 1-alpha synthesis during early development in sea urchins. AB - We have isolated a cDNA clone encoding elongation factor 1-alpha (EF1-alpha) and used probes prepared from this cDNA to measure levels of EF1-alpha transcripts during early development. We also determined the fraction of EF1-alpha transcripts in polysomes during this time period. Following the blastula stage there is a sharp increase in the amount of EF1-alpha mRNA. This pattern of accumulation is similar to other previously described sea urchin mRNAs. However, while the level of EF1-alpha mRNA is increasing, the fraction of EF1-alpha mRNA in polysomes decreases. Thus, there is an apparently counter-productive decrease in efficiency of recruitment into polysomes occurring concurrently with an increase in the overall amount of EF1-alpha mRNA. PMID- 2257983 TI - A survey of adolescents with epilepsy. AB - Thirty-four adolescents with epilepsy, controls matched for age and sex (A) and controls matched for age, sex and general ability (B), were studied. The adolescents with epilepsy were more likely to arrive at school by car or taxi and to have more difficult behaviour in class. Competitive sports were less popular with them and significantly fewer anticipated ever driving a car. Illness and parental marital problems were not a feature of their families. Their comprehension of reading material was significantly poorer than that of control group A. Within the group, the lowest over-all reading scores were found in children with myoclonic seizures, partial seizures with secondary generalisation, or generalised tonic-clonic seizures; and in those whose EEG findings included two-per-second spike and wave, photosensitivity, generalised slow waves, or generalised spike and wave of non-specific frequency. Right focal slow waves, sharp waves and spikes on EEG were associated with problems of comprehension, even when the over-all reading score was acceptable. PMID- 2257984 TI - EEG monitoring of therapy for neonatal seizures. AB - Eleven neonates with seizures had continuous EEGs recorded before and up to several hours after administration of anticonvulsant therapy. Six of seven babies given phenobarbitone responded clinically, but in four of these the EEG showed that seizure discharges either persisted or recurred within two hours. Chloral hydrate had no immediate effect in one case and only a doubtful influence on EEG seizure activity in another. Three babies were given benzodiazepines: after an apparently rapidly effective bolus dose of diazepam, recurrence of seizure discharges was almost immediate. Infusions of diazepam or clonazepam eventually were associated with persistent control of clinical and EEG seizures. In the treatment of neonatal seizures, conventional anticonvulsants are rarely completely effective: EEG monitoring is essential for optimal therapeutic intervention. PMID- 2257985 TI - Conversion disorders in childhood: a retrospective follow-up study of 84 inpatients. AB - The medical histories of 84 children who had been diagnosed as having conversion disorder were reviewed in a follow-up study, and the validity of this diagnosis was examined. The female:male ratio was 2.1:1, although below the age of 10 the ratio was almost equal. The medical histories of 62 per cent of the patients showed an organic illness, and 51 per cent had various slight to moderate EEG disturbances. The validity of the diagnosis was very high: only five were found to have organic disease during the follow-up period. Children with symptoms of conversion disorder should receive appropriate medical investigations, but the authors question whether extensive investigations could not be replaced by screening tests, combined with early psychiatric intervention. PMID- 2257986 TI - Widened subarachnoid space in pre-discharge cranial ultrasound: evidence of cerebral atrophy in immature infants? AB - The authors examined the incidence of widened subarachnoid spaces (SAS) among 75 infants with birthweights less than or equal to 1250g, and their significance in developmental outcome. Nine of 30 infants with gestations less than or equal to 27 weeks had widened SAS in their pre-discharge ultrasound scans. Three of the nine, including two with periventricular leukomalacia (PVL), had late-onset ventricular enlargement, unrelated to intraventricular haemorrhage (IVH): all three were developmentally impaired. The other six infants without ventricular enlargement developed normally, including one with IVH. Five of the remaining 21 infants with gestations less than or equal to 27 weeks and without widened SAS were developmentally impaired. Widened SAS was not associated with a significantly increased risk of developmental impairment; ventricular enlargement and PVL were the only significant factors. The authors conclude that an isolated finding of widened SAS is not predictive of impairment in immature infants. PMID- 2257987 TI - An epidemiological study on severe mental retardation among schoolchildren in Bologna, Italy. AB - The prevalence, causal origin of and impairments associated with severe mental retardation (SMR) were investigated among all school-age children (six to 13 years) living in the city of Bologna, Italy. 90 children (57 boys, 33 girls) with IQs less than or equal to 50 were identified. The prevalence of SMR was 4.2 per 1000 for males, 2.5 per 1000 for females and 3.4 per 1000 for both sexes. Causal origin was prenatal for 33.3 per cent, perinatal for 14.4 per cent, combined pre- and perinatal for 5.6 per cent and postnatal for 13.3 per cent. Another 12.3 per cent of the children with IQs less than or equal to 50 had autism or childhood psychosis, while there was no evident cause of mental retardation for the remaining 21.1 per cent. 50 per cent had at least one associated physical or neurological impairment other than mental retardation, with epilepsy and cerebral palsy predominating. PMID- 2257988 TI - Objective test of the quality of motor function of children with cerebral palsy: preliminary study. AB - An objective test of motor function would enable better evaluation of various treatment programmes for children with cerebral palsy. The use of tri-axial accelerometry was investigated in 36 children with cerebral palsy and in 53 children without disabilities. Variables discriminated well between able-bodied and disabled children, and there was a high level of retest reliability. The technique requires further development, but shows promise of providing the ability to gather objective data about the quality of motor function. PMID- 2257989 TI - Cerebral lesions in preterm infants after tocolytic indomethacin. AB - The incidence and type of cerebral lesions in 159 infants born before 30 weeks gestation were studied, using ultrasound. Indomethacin was given as part of tocolytic management to mothers with a high incidence of early rupture of membranes and preterm labour; and 76 fetuses were exposed to the drug as a result. For the remaining 83 pregnancies, in which there was a high incidence of chronic fetal distress and in utero hypoxia, tocolysis was either not started or limited to fenoterol. The neonatal course was similar for both groups of infants, except that patent ductus arteriosus was less commonly diagnosed in the 76 infants exposed to indomethacin. However, the incidence of periventricular leukomalacia was increased among infants exposed to any tocolytic agent; and cystic lesions occurred more commonly in those exposed to indomethacin. PMID- 2257990 TI - The operculum syndrome: an unusual complication of tuberculous meningitis. AB - The operculum syndrome, not previously documented as a complication of tuberculous meningitis, is described in a three-year-old African boy. The appearance on CT scan correlates radiographically with anatomical descriptions of the operculum syndrome, and is useful in distinguishing the condition from pseudobulbar palsy. PMID- 2257991 TI - Anti-epileptic drug monitoring: an overview. PMID- 2257993 TI - Ophthalmoplegia and Arnold-Chiari malformation without hydrocephalus. PMID- 2257992 TI - Ultrasound measurement of urine volume. PMID- 2257994 TI - Rectal chloral hydrate for alternating hemiplegia of childhood. PMID- 2257995 TI - Acute and chronic effects of hyperglycaemia on glucose metabolism. AB - In normal man, several hormonal and metabolic adjustments allow the maintenance of the blood glucose concentration within narrow limits. Hyperglycaemia participates in this regulation via stimulation of glucose disposal and inhibition of glucose production. The effects are mediated, in addition to changes in insulin and glucagon secretion, by the mass-action effect of glucose. In both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients, hyperglycaemia, by mass-action abnormally elevates the basal glucose utilization rate but compensates for reduced postprandial insulin-stimulated glucose disposal. When exposed to chronic hyperglycaemia, the body tissues seem to protect themselves, at least partly, against excessive glucose utilization. These protective mechanisms include both a reduction in insulin stimulated glucose disposal and insulin secretion. Chronic hyperglycaemia may also reduce non-insulin-dependent glucose utilization, at least in rats. In Type 1 diabetic patients with normal peripheral insulin concentrations, chronic hyperglycaemia per se could be a major cause of insulin resistance. In Type 2 diabetic patients, insulin resistance is often already present before the development of overt fasting hyperglycaemia. At the diabetic stage, hyperglycaemia could, however, maintain a self-perpetuating cycle, where the deleterious effects of high glucose concentrations on insulin action and secretion cause further deterioration of glycaemic control. The biochemical basis for hyperglycaemia-induced insulin resistance is still far from clear, but could involve changes in the glucose transporter number and gene expression. PMID- 2257996 TI - Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos. AB - Neural tube defects in infants of diabetic mothers constitute an important and frequent cause of neonatal mortality/morbidity and long-term chronic handicaps. The mechanism by which normal neural tube fusion occurs is not known. The failure of rostral neural tube fusion seen in mouse embryos incubated in the presence of excess-D-glucose can be significantly prevented by the supplementation of myo inositol to the culture medium. This protective effect of myo-inositol is reversed by indomethacin, an inhibitor of arachidonic acid metabolism leading to prostaglandin synthesis. Prostaglandin E2 added to the culture medium completely protects against the glucose-induced neural tube defect. These data suggest that the failure of neural tube fusion seen in diabetic embryopathy is mediated through a mechanism involving abnormalities in both the myo-inositol and arachidonic acid pathways, resulting in a functional deficiency of prostaglandins at a critical time of neural tube fusion. PMID- 2257997 TI - On the determination of basal glucose production rate in patients with type 2 (non-insulin-dependent) diabetes mellitus using primed-continuous 3-3H-glucose infusion. AB - Using primed-continuous 3-3H-glucose infusion, basal glucose production rate has been reported to be 140% higher than normal or almost normal in hyperglycaemic patients with Type 2 (non-insulin-dependent) diabetes mellitus. To determine whether these markedly different results could be due to the mode of priming: fixed or adjusted, or the mode of calculation: steady state or non-steady state equations, we studied 11 patients with Type 2 diabetes (fasting plasma glucose 8 20 mmol/l). For 6 h 3-3H-glucose (0.40 microCi/min) was infused preceded by a priming dose of 40 microCi (fixed priming), or 40 microCi.plasma glucose (mmol/l).5(-1) (adjusted priming). In diabetic patients the plasma glucose concentration was not constant but declined 0.52 +/- 0.07 mmol.l-1.h-1. Furthermore, the rate of fall was correlated to the fasting plasma glucose concentration (r = 0.90, p less than 0.01). Thus, the fasting state was not a steady state condition. Using adjusted priming a constant tracer steady state level was obtained within 60 min. In contrast, using fixed priming tracer steady state was not reached within 6 h. The initial tracer level was far below, and increased in time towards the steady state level observed after adjusted priming. Consequently, using Steele's equations after fixed priming, glucose production rates calculated after 90-120 min were overestimated in proportion to fasting hyperglycaemia. IN CONCLUSION: The fasting state in patients with Type 2 diabetes is not a steady state condition. Adjusted priming seems most appropriate in Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2257998 TI - Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy. AB - Nerve biopsies were obtained from 27 patients with diabetic neuropathy. All had a symmetric distal sensory and autonomic neuropathy or a purely sensory neuropathy. Mean age was 39.8 years (range 23-57 years). Two patients had Type 2 (non-insulin dependent) diabetes mellitus and the remainder Type 1 (insulin-dependent) diabetes. Morphometric observations on endoneurial capillaries were compared with results from organ donor control cases and from patients with type 1 hereditary motor and sensory neuropathy. The area of the lumen of the capillaries did not differ between the three groups. The area occupied by the capillary endothelial cells in transverse section and the number of endothelial cell nuclei were increased both in the patients with diabetic neuropathy and hereditary motor and sensory neuropathy, as was the thickness of the surrounding basal laminal zone. 'Closure' of endoneurial capillaries in diabetic neuropathy, reported in another study, was not confirmed. Capillary density and nearest-neighbour distances were similar in the diabetic and organ donor control cases. Capillary density was reduced in the patients with hereditary motor and sensory neuropathy, this being related to increased fascicular area consequent upon the presence of hypertrophic changes. The presence of thickening of the pericapillary basal laminal zone and endothelial cell hyperplasia both in diabetic and hereditary motor and sensory neuropathy, the latter being a neuropathy in which a vascular basis can be discounted, makes it difficult to use such changes as an argument favouring a vascular cause for diabetic neuropathy. There were differences in the basal laminal zone between the diabetic and hereditary motor and sensory neuropathy cases suggesting that the reduplicated basal lamina was more persistent in the diabetic patients. PMID- 2258000 TI - Expression of insulin regulatable glucose transporters in skeletal muscle from type 2 (non-insulin-dependent) diabetic patients. AB - A prominent feature of Type 2 (non-insulin-dependent) diabetes mellitus is the inability of insulin to appropriately increase the transport of glucose into target tissue. In adipocytes from individuals with Type 2 diabetes, insulin resistance has been shown to be associated with a depletion of glucose transporters. Similarly, streptozotocin induced diabetes causes a diminished expression of the insulin regulatable glucose transporter in rat adipocytes. The expression of this glucose transporter isoform has not yet been investigated in muscle tissue from patients with Type 2 diabetes. We have measured the content of the insulin regulatable glucose transporter in a vesicular fraction isolated from muscle biopsies from fasting individuals with Type 2 diabetes and control subjects, and we found that the number of the insulin regulatable glucose transporters expressed in skeletal muscle was unaffected by Type 2 diabetes (0.208 vs 0.205, arbitrary units, p greater than 0.5, control subjects and diabetic patients). Thus, the decreased glucose disposal in Type 2 diabetes is not associated with a diminished number of insulin regulatable glucose transporters. PMID- 2257999 TI - Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy. AB - Genetic predisposition to essential hypertension, represented by maximal erythrocyte sodium/lithium countertransport activity, has been suggested as a marker for the risk of developing clinical nephropathy in Type 1 (insulin dependent) diabetes mellitus. To evaluate this hypothesis we measured arterial blood pressure and maximal sodium/lithium countertransport activity of erythrocytes in 80 parents of 49 Type 1 diabetic patients with clinical nephropathy, 78 parents of 49 normoalbuminuric patients and 17 age-matched non diabetic individuals. The two diabetic groups were carefully matched. In the two groups of parents blood pressure and cell sodium/lithium countertransport activity showed no significant differences (137/83 vs 133/81 mm Hg and 0.33 vs 0.32 mmol/(1 cells x h) respectively). The proportion of parents who had died or received antihypertensive drugs was similar in the two groups. The patients with Type 1 diabetes had significantly higher sodium/lithium countertransport compared to the 39 non-diabetic control subjects independently of the presence or absence of nephropathy (p less than 0.002). However, patients with nephropathy tended to have higher sodium/lithium countertransport activity than normoalbuminuric patients (0.48 vs 0.41 mmol/(1 cells x h), p = 0.06). We conclude that genetic predispositions to essential hypertension and increased maximal erythrocyte sodium/lithium countertransport activity do not appear to be risk markers for the development of clinical nephropathy in Type 1 diabetic patients. PMID- 2258001 TI - Islet amyloid polypeptide (amylin): no evidence of an abnormal precursor sequence in 25 type 2 (non-insulin-dependent) diabetic patients. AB - Islet amyloid polypeptide is the major protein component of the islet amyloid of patients with Type 2 (non-insulin-dependent) diabetes mellitus. Since the synthesis of a structurally abnormal or mutant protein may contribute to the formation of amyloid deposits, we have examined the possibility that a mutant form of islet amyloid polypeptide or its precursor contributes to the formation of islet amyloid in Type 2 diabetic patients. We have sequenced the islet amyloid polypeptide precursor coding regions of the gene of 25 patients with Type 2 diabetes. Genomic DNA fragments corresponding to exon 2 and 3 of the islet amyloid polypeptide gene were amplified from patients' peripheral blood leucocyte DNAs using the polymerase chain reaction and specific oligonucleotide primer sets, and then directly sequenced. The nucleotide sequences of the amplified regions of both alleles of the islet amyloid polypeptide gene of these 25 patients were identical to one another and to the sequence of an islet amyloid polypeptide allele isolated from a human fetal liver genomic library. These findings suggest that a primary structural abnormality of islet amyloid polypeptide or its precursor is unlikely to play a significant role in the formation of islet amyloid in Type 2 diabetic patients. PMID- 2258002 TI - The first phase insulin response to intravenous glucose is highly reproducible. AB - To determine the reproducibility of the first phase insulin response to intravenous glucose, ten normal subjects underwent two intravenous glucose tolerance tests separated by at least two weeks. Intravenous dextrose (0.3 g/kg) was administered over 2 min by continuous infusion and arterialised-venous samples were taken from a retrogradely cannulated hand vein in the opposite arm. Within subjects, median coefficient of variation for the 3 min insulin was 4.0% (range 1.2-24.3%) and median coefficient of variation for the 0-10 min area was 6.7% (range 1.7-18.8%). These coefficients of variation are close to those of the assay itself (less than 10%). Despite this, between subject responses varied by greater than sixfold. In conclusion, contrary to previous reports the intravenous glucose tolerance test is highly reproducible. This makes it a very valuable tool for further studies of the pathogenesis of diabetes. PMID- 2258003 TI - Raised temperature reduces the incidence of diabetes in the NOD mouse. AB - An association between the incidence of childhood Type 1 (insulin-dependent) diabetes mellitus and the average yearly temperature in different countries has been reported, the incidence being higher in countries with a lower mean temperature. We have studied the effect of environmental temperature on the incidence of diabetes in an animal model of Type 1 diabetes, the non-obese diabetic (NOD) mouse. Female NOD mice were divided at weaning, with one group placed at a higher temperature (mean 23.7 +/- 1.7 degrees C) and the other at a lower temperature (21.0 +/- 1.8 degrees C). At 20 weeks of age 6 of 16 mice at lower temperature and 1 of 17 mice at higher temperature had developed diabetes (p less than 0.02); at 30 weeks 10 of 16 and 5 of 17 mice had developed diabetes (p less than 0.05). Non-diabetic animals in the low temperature group had a higher food intake than those in the high temperature group between 13-15 weeks of age (28.0 +/- 1.2 g/week vs 24.8 +/- 0.7 g/week, p less than 0.05). In a parallel experiment, histological examination showed that there were similar degrees of insulitis in the high and low temperature groups at seven weeks of age. We conclude that environmental temperature can affect the incidence of diabetes in the NOD mouse and that this may be related to alterations in food intake. PMID- 2258004 TI - The Fourth International Workshop on the Standardisation of Insulin Autoantibody Workshop. PMID- 2258005 TI - Which battery of cardiovascular autonomic function tests--suggestion for a rational diagnostic model. PMID- 2258006 TI - Information resources useful in forensic toxicology. AB - This paper addresses information resources available to forensic toxicologists. The approach taken here is to discuss those resources found useful in problem solving situations. First, attempt to obtain information from someone familiar with the problem. This is generally the most efficient mechanism to use. The next most efficient mechanism is to search the published literature, electronically using bibliographic databases, if possible. The least efficient method of obtaining information is to go into the laboratory and generate the desired information. In many situations, however, the problem must be solved, or the information confirmed, in the laboratory. Suggested sources of information have been listed in the appendices. These are not intended to be exhaustive, but rather to stimulate and direct the access to information resources. PMID- 2258007 TI - Biliary excretion appears rate limiting for hepatic elimination of benzo[a]pyrene by temperature-acclimated rainbow trout. AB - Previous work demonstrated that mixed function oxidase activities of hepatic microsomes from cold- and warm-acclimated rainbow trout were similar when assayed at temperatures to which fish were acclimated. This "ideal temperature compensation" was partially explained by constitutive differences in microsomes. In the work reported here, rainbow trout were acclimated at 10 or 18 degrees C for 4 weeks and then ip injected with 10 mumol [3H] or [14C]benzo[a]pyrene (BP)/kg in one of two temperature regimens. First, fish were acclimated and exposed at the same temperature and killed after 4, 24, or 48 hr. Concentrations of [3H]BP equivalents in liver, bile, and fat but not in plasma, muscle, intestine, gill, or kidney increased with time. There were no differences in hexane or ethyl acetate extractable [3H] or [14C]BP tissue concentrations in 10 and 18 degrees C-acclimated fish exposed at their acclimation temperatures. At 24 hr after injection, biliary excretion of [3H]BP equivalents was about twofold higher at 18 degrees C than at 10 degrees C. Therefore, warmer temperature stimulated biliary excretion without a marked effect on in vivo BP metabolism. In the second regimen, 10 and 18 degrees C-acclimated fish were shifted to 14 degrees C, injected with [3H] or [14C]BP 1 hr later, and killed after an additional 24 hr. There were no differences in tissue concentrations of total [3H]BP equivalents between acclimation groups at 14 degrees C. However, the biliary concentration of [14C]BP not extracted by ethyl acetate was significantly higher in bile from 10 degrees C-acclimated fish than from 18 degrees C acclimated fish when both groups were exposed at 14 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258009 TI - Biochemical changes in rat erythrocytes caused by ethylene oxide exposure. AB - When Wistar male rats were exposed to ethylene oxide (EtO) at a concentration of about 500 ppm, 6 hr a day, 3 days a week for 2, 6, or 13 weeks, hematological examination showed macrocytic, normochromic anemia with a high reticulocyte count. This result raised the possibility that the hemolytic process was responsible for the anemia. Thus, the following possible causes of hemolysis were investigated with erythrocytes obtained from control and EtO-exposed rats. (1) Metabolism in erythrocytes; (a) Hexose monophosphate cycle: The activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, or glutathione peroxidase was not affected, but the activity of glutathione reductase (GR) significantly decreased and did not recover by the addition of flavin adenine dinucleotide. Reduced glutathione content also decreased and the glutathione stability test was positive. (b) Embden-Meyerhof pathway: Adenosine triphosphate content did not decrease. (c) Lapoport-Luebering cycle: 2,3 Diphosphoglycerate content was not affected. (2) Membrane alterations: Osmotic fragility was not affected and the activity of acetylcholine esterase in the ghost membranes of the exposed group increased. (3) Hemoglobin stability: The heat test and the isopropanol test were negative. GR has an important function in maintaining the reducing power in erythrocytes, and the decrease in the activity caused by EtO induced an alteration of the glutathione stability. Although the mechanism of EtO-induced anemia could not be clearly explained, the inhibition of GR activity might be related to the anemia. PMID- 2258008 TI - Potentiation of CCl4 and CHCl3 hepatotoxicity and lethality by various alcohols. AB - Various aliphatic alcohols potentiate the toxicity of a wide range of xenobiotics including several haloalkanes. The present series of experiments were designed to test: (i) whether a single subtoxic dose of alcohol can potentiate CCl4 and CHCl3 hepatoxicity, and (ii) whether this potentiation leads to greater animal lethality. Selected members of a homologous series of straight chain alcohols were chosen for this study. Methanol, ethanol, isopropanol, t-butanol, pentanol, hexanol, octanol, decanol, and eicosanol at equimolar doses (10 mmol/kg) were tested in the present investigation. Each alcohol was administered orally to male Sprague-Dawley rats (175-250 g) 18 hr prior to a single oral administration of CCl4 or CHCl3. Liver injury was assessed by plasma transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST) and histopathological examination of liver sections 24 hr after the halomethane treatment. None of these alcohols alone increased plasma ALT or AST significantly, whereas CCl4 or CHCl3 administration to alcohol-treated animals resulted in significant elevation of plasma transaminases. Eicosanol (20-carbon alcohol) did not potentiate the toxicity of either halomethane. Methanol, ethanol, isopropanol, and decanol in combination with CCl4 caused massive liver damage but failed to augment CCl4 lethality. t-Butanol, pentanol, hexanol, and octanol significantly decreased the LD50 of CCl4. The hepatotoxic effects of CHCl3 were potentiated by all of the alcohols and the LD50s were also decreased significantly. On a comparative basis, alcohol-potentiated CHCl3 toxicity was greater than the toxicity of CCl4. These findings indicate that even though halomethane liver injury might be potentiated by alcohols, the underlying mechanisms differ among alcohols since not all alcohols potentiate the lethal effects of these halomethanes. PMID- 2258010 TI - Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats. AB - 2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0, 250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly (p less than 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg. PMID- 2258011 TI - Benzene hemoglobin adducts in mice and rats: characterization of formation and physiological modeling. AB - Benzene is a myelotoxin and a human leukemogen. Humans are exposed to this compound, both occupationally and environmentally. This study was conducted to determine whether formation of benzene-derived adducts with blood hemoglobin (Hb) can be used as a biomarker of exposure to benzene. B6C3F1 mice and F344/N rats were given 0.1 to 10,000 mumol [14C]benzene/kg body wt, orally. Twenty-four hours later, animals were euthanized, and globin was isolated from blood samples. The globin was analyzed by liquid scintillation spectrometry for the presence of [14C]benzene-derived adducts. Hb adduct formation was linear with respect to dose for amounts of up to 500 mumol [14C]benzene/kg body wt, for both rodent species. Within this linear dose-response range, mice formed adducts from [14C]benzene approximately 3.5 times less efficiently [0.022 +/- 0.010 (pmol adducts/mg globin)/(mumol/kg body wt dose)] than did rats [0.076 +/- 0.014 (pmol adducts)/(mumol/kg body wt dose)]. Benzene-derived Hb adducts also accumulated linearly when mice and rats were given up to three daily doses of 500 mumol [14C]benzene/kg body wt. These data were used to develop a physiological model for benzene-derived Hb adduct formation. Both first-order and saturable pathways for adduct formation were incorporated. The results showed that the model simulated the levels of Hb adducts in both mice and rats after oral exposures to benzene and predicted the levels of Hb adducts present after inhalation exposure. These studies suggest that Hb adducts might be useful biomarkers for human exposures to benzene. PMID- 2258012 TI - The immunotoxicity of three nickel compounds following 13-week inhalation exposure in the mouse. AB - Groups of B6C3F1 mice were exposed to aerosols of nickel subsulfide (Ni3S2), nickel oxide (NiO), or nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day, 5 days per week for 65 days to determine the immunotoxicity of these compounds. Exposure concentrations were 0.11, 0.45, and 1.8 mg Ni/m3 for Ni3S2, 0.47, 2.0, and 7.9 mg Ni/m3 for NiO; and 0.027, 0.11, and 0.45 mg Ni/m3 for NiSO4. Thymic weights were decreased only in mice exposed to 1.8 mg Ni/m3 Ni3S2. Increased numbers of lung associated lymph nodes (LALN), but not spleen nucleated cells, were seen with all compounds. Nucleated cells in lavage samples were increased in mice exposed to the highest concentrations of NiSO4 and NiO and to 0.45 and 1.8 mg Ni/m3 Ni3S2. Increased antibody-forming cells (AFC) were seen in LALN of mice exposed to 2.0 and 7.9 mg Ni/m3 NiO and 1.8 mg Ni/m3 Ni3S2. Decreased AFC/10(6) spleen cells were observed in mice exposed to NiO, and decreased AFC/spleen were seen for mice exposed to 1.8 mg Ni/m3 Ni3S2. Only mice exposed to 1.8 mg Ni/m3 Ni3S2 had a decrease in mixed lymphocyte response. All concentrations of NiO resulted in decreases in alveolar macrophage phagocytic activity, as did 0.45 and 1.8 mg Ni/m3 Ni3S2. None of the nickel compounds affected the phagocytic activity of peritoneal macrophages. Only 1.8 mg Ni/m3 Ni3S2 caused a decrease in spleen natural killer cell activity. Results indicate that inhalation exposure of mice to nickel can result in varying effects on the immune system, depending on dose and physicochemical form of the nickel compound. These nickel-induced changes may contribute to significant immunodysfunction. PMID- 2258013 TI - The in vitro activation of cyclophosphamide in the Hydra Developmental Toxicology Assay. AB - The proteratogen cyclophosphamide (CP) was tested in the Hydra Assay in the presence and absence of an in vitro metabolic activation package (MAP) consisting of rat hepatic microsomes (0.06 nmol P450/ml), 500 microM NADPH, and 25 microM MgCl. This metabolic system was developed through a series of interrelated biochemical and biological assays to provide maximum cytochrome P450 mixed function monooxygenase (MFO) metabolic capacity while controlling the inherent toxicity of the hepatic preparation and the attendant cofactors. Bioactivation of CP was confirmed under standard hydra assay conditions of pH 7.0 and 20 degrees C and compared with activation at 37 degrees C. Estimation of total metabolic capacity and verification of activation were made through the appearance of alkylating metabolites both in the absence and in the presence of hydra. Chemical exposure was maintained throughout the 92 +/- 2 hr assay with periodic renewal of media (and additives) at 4, 20, 28, 42, and 66 hr of incubation. Inclusion of bioactivation increased the toxicity of CP by two orders of magnitude. The minimal affective concentration in the adult and developmental portions of the assay was decreased from 4000 to 20 micrograms CP/ml and from 1000 to 4 micrograms CP/ml, respectively. By limiting the inherent toxicity of the MFO package, it was possible to avoid pulse-type exposures and ensure that all ontogenic stages were exposed to active metabolites. The addition of metabolic activation capacity to an in vitro assay, while not essential, markedly enhances its utility and breadth of application in developmental toxicity safety evaluations. PMID- 2258014 TI - Hepatic aryl hydrocarbon hydroxylase and cytochrome P450 induction following the transpulmonary absorption of TCDD from intratracheally instilled particles. AB - Inhalation of particles contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) will be an increasingly important route of human exposure in light of the increased utilization of municipal waste incineration and the resultant emission of contaminated materials into the environment. The potential for pulmonary absorption of the compound from respirable particles was assessed in the present study following the intratracheal instillation of TCDD (1) as a contaminant of gallium oxide particles and (2) in a corn oil vehicle. Groups of five female Sprague-Dawley rats received 0, 0.005, 0.055, 0.55, or 5.5 micrograms/kg TCDD in a single instillation and were euthanized 4 days later. Absorption was characterized by enzyme induction [aryl hydrocarbon hydroxylase (AHH) activity and total cytochrome P450] and histopathological examination of the liver. Induction of hepatic enzymes was dose-dependent with both treatment regimes. Up to an 18-fold increase in AHH and an 80% increase in cytochrome P450 were observed in treated animals. Induction was slightly higher when animals received TCDD in corn oil than when animals received TCDD-contaminated particles and was relatively comparable to induction following oral exposure. Similar results were obtained when animals were treated with particles contaminated up to 4 weeks prior to instillation. Characteristics of TCDD-induced hepatotoxicity, including enlarged hepatocytes and fatty infiltration, were apparent in treated rats, but were not present in vehicle-instilled animals. These results indicate that systemic effects occur following pulmonary exposure to TCDD and that inhalation may be an important route of exposure for TCDD. PMID- 2258015 TI - Percutaneous absorption of [14C]DDT and [14C]benzo[a]pyrene from soil. AB - The objective was to determine percutaneous absorption of DDT and benzo[a]pyrene in vitro and in vivo from soil into and through skin. Soil (Yolo County 65 California-57-8; 26% sand, 26% clay, 48% silt) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with [14C]-labeled chemical at 10 ppm. Acetone solutions at 10 ppm were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 24-hr skin application time. With acetone vehicle, DDT (18.1 +/- 13.4%) readily penetrated into human skin. Significantly less DDT (1.0 +/- 0.7%) penetrated into human skin from soil. DDT would not partition from human skin into human plasma in the receptor phase (less than 0.1%). With acetone vehicle, benzo[a]pyrene (23.7 +/- 9.7%) readily penetrated into human skin. Significantly less benzo[a]pyrene (1.4 +/- 0.9%) penetrated into human skin from soil. Benzo[a]pyrene would not partition from human skin into human plasma in the receptor phase (less than 0.1%). Substantivity (skin retention) was investigated by applying 14C-labeled chemical to human skin in vitro for only 25 min. After soap and water wash, 16.7 +/- 13.2% of DDT applied in acetone remained absorbed to skin. With soil only 0.25 +/- 0.11% of DDT remained absorbed to skin. After soap and water wash 5.1 +/- 2.1% of benzo[a]pyrene applied in acetone remained absorbed to skin. With soil only 0.14 +/- 0.13% of benzo[a]pyrene remained absorbed to skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258016 TI - Ethylene glycol monopropyl ether: a developmental toxicity study in rabbits. AB - To determine the potential developmental toxicity of ethylene glycol monopropyl ether (EGPE), groups of pregnant New Zealand white rabbits were exposed to target concentrations of 0, 125, 250, or 500 ppm EGPE vapors for 6 hr a day on Days 6-18 of gestation. Maternal effects included a slight reduction in feed consumption during the first week of treatment at the 250- and 500-ppm exposure levels and slightly reduced body weight gain at the 500-ppm level compared to those of the controls, but the differences were not statistically significant. One doe exposed to 500 ppm had red-colored urine during the 24-hr period following the second exposure. Hematologic determinations, absolute and relative organ weights, and observations at necropsy revealed no treatment-related maternal effects. Reproductive indices, i.e., pregnancy rate, number of corpora lutea, implantation sites, viable fetuses, early and late resorptions, fetal body weights, fetal sex ratio, and the gravid uterine and corrected body weights, were not affected by exposures to EGPE. The occurrences of external and internal soft tissue malformations and variations and the incidences of skeletal malformations in the EGPE-exposed groups were not significantly different from those in the control group. Common skeletal variations, in many instances, were seen less frequently in EGPE-exposed fetuses than in control fetuses. In those cases where the incidence of fetuses with a skeletal variation was greater for EGPE-exposed fetuses than that for control fetuses, the number of litters involved was not significantly different from that of the control group. Thus, EGPE vapor concentrations as high as 500 ppm did not produce teratogenicity or other developmental toxicity in the rabbit conceptus. PMID- 2258017 TI - Effects of methyl benzimidazolecarbamate during early pregnancy in the rat. AB - Methyl 2-benzimidizolecarbamate (MBC), an agricultural fungicide, and its parent compound benomyl have adverse reproductive effects on male rats and exhibit embryotoxicity, including teratogenicity, when administered to rats during mid to late pregnancy. This study was designed to assess potential maternal effects of MBC during early pregnancy, to distinguish maternal from embryotoxic effects of the chemical, and to differentiate between early pregnancy failure and late embryonic loss. MBC was administered to rats by gavage at 0, 25, 50, 100, 200, 400, and 1000 mg/kg/day during Days 1 through 8 of pregnancy (Day 0 = sperm positive). A range of maternal and embryonic parameters was assessed following euthanasia on Day 9, including the number of implantation sites, body weight gain, uterine weight, implantation site size, and serum ovarian and pituitary hormones. In a separate experiment, pseudopregnant rats were administered 0 or 400 mg/kg/day MBC during Days 1-8, received bilateral uterine decidual induction on Day 4, and were killed on Day 9 at which time the decidual cell response was evaluated as a measure of uterine competency. When dosages of up to 400 mg/kg/day of MBC were administered during early pregnancy, the chemical had no significant effect on any measured parameter but a trend toward increased resorptions was evident. The 1000 mg/kg/day dosage of MBC produced reductions in body weight gain, implantation site weight, and serum LH and an increase in serum estradiol. When administered during pseudopregnancy, 400 mg/kg/day MBC partially reduced uterine decidual growth but affected no other parameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258018 TI - Risk extrapolation for chlorinated methanes as promoters vs initiators of multistage carcinogenesis. AB - "Cell-kinetic multistage" (CKM) models account for clonal growth of intermediate, premalignant cell populations and thus distinguish somatic mutations and cell proliferation as separate processes that may influence observed rates of tumor formation. This paper illustrates the application of two versions of a two-stage CKM model (one assuming exponential and the other geometric proliferation of intermediate cells) for extrapolating cancer risk potentially associated with exposure to carbon tetrachloride, chloroform, and dichloromethane, three suspect human carcinogens commonly present in trace amounts in groundwater supplies used for domestic consumption. For each compound, the models were used to calculate a daily oral "virtually safe dose" (VSD) to humans associated with a cancer risk of 10(-6), extrapolated from bioassay data on increased hepatocellular tumor incidence in B6C3F1 mice. Exposure-induced bioassay tumor responses were assumed first to be due solely to "promotion" (enhanced proliferation of premalignant cells, here associated with cytotoxicity), in accordance with the majority of available data on in vivo genotoxicity for these compounds. Available data were used to model dose response for induced hepatocellular proliferation in mice for each compound. Physiologically based pharmacokinetic models were used to predict the hepatotoxic effect (metabolized) dose as a function of parent compound administered dose in mice and in humans. Resulting calculated VSDs are shown to be from three to five orders of magnitude greater than corresponding values obtained assuming each of the compounds is carcinogenic only through induced somatic mutations within the CKM framework. Key issues and uncertainties in applying CKM models to risk assessment for cancer promoters are discussed. PMID- 2258019 TI - Assessment of hepatic indicators of subchronic carbon tetrachloride injury and recovery in rats. AB - To determine the course of hepatic recovery from subchronic oral administration of carbon tetrachloride (CCl4), male F-344 rats were gavaged with 0, 20, or 40 mg CCl4/kg, 5 days/week, for 12 weeks. Exposure to CCl4 caused dosage-dependent increases in relative liver weight and the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and cholesterol as well as a dosage-dependent decrease in hepatic cytochrome P450. Centrilobular hepatocellular vacuolar degeneration, necrosis, and cirrhosis occurred at both 20 and 40 mg/kg, with dosage-dependent severity. Reversibility of these reported effects varied with parameter. By Day 8 postexposure, necrosis had disappeared and all serum indicators and cytochrome P450 had returned to control levels. By Day 15 postexposure, the severity of the vacuolar degeneration had decreased. Reversibility of cirrhosis was dosage dependent; complete recovery occurred in the low- but not the high-dose group by Day 15. The disappearance of the increase in relative liver weight was also dependent on dosage; the low- but not the high-dose group had returned to the control level by Day 22. In an attempt to measure persistent hepatic damage, liver uptake relative to the spleen was determined for a sulfur colloid labeled with technetium-99m and for tritiated 2-deoxyglucose. Neither method consistently measured hepatic damage in cirrhotic livers due, in part, to the high degree of variability in the tracer uptake data. PMID- 2258020 TI - Toxicological mechanisms of implantation failure. AB - Implantation in mammals requires the successful completion of a series of integrated phenomena, including uterine preparation, synchronized embryo transport, embryonic attachment, uterine transformation, placental development, and the requisite hormonal milieu to support each step. Potential for toxic interference with early pregnancy exists at several points in this course of events via a variety of anatomical and physiological sites. An improved understanding of the mechanisms of implantation failure due to toxic insult is necessary in order to assess risks of reproductive toxicants to the human female population. As an approach to providing such information, a panel of tests has been assembled and developed to probe the mechanisms by which chemicals affect fertility in rodents. These assessments are performed only if adverse effects on litter size or pregnancy are evident from previous reproductive studies. The evaluation of methoxychlor, a weakly estrogenic pesticide, has served to partially validate this panel. The early pregnancy protocol provides dose response information on the effects of short-term exposure of animals to compounds during early pregnancy. The pre- vs postimplantation protocol assesses the differential effects of such chemicals on the physiological events unique to the periods immediately preceding and following implantation. The decidual cell response technique can distinguish embryotoxicity from direct effects of toxicants on uterine or other physiological functions. Embryo transport rate analysis evaluates the potential for early embryonic loss via accelerated or retarded arrival of embryos into the uterus. The panel thus permits the determination of the site or sites of toxic insult and the mechanisms by which environmental toxicants may compromise fertility following short-term exposure during early pregnancy. PMID- 2258021 TI - Subchronic oral toxicity of triethyl lead in the male weanling rat. Clinical, biochemical, hematological, and histopathological effects. AB - This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt. PMID- 2258022 TI - Acute inhalation exposure to epichlorohydrin transiently decreases rat sperm velocity. AB - The effect of inhaled epichlorohydrin on rat sperm motility characteristics was evaluated. Male F-344 rats were exposed to 100 ppm epichlorhydrin via inhalation for 4 hr in the morning of Day 0 and killed immediately and on Days 1, 2, 6, and 14 postexposure. Videotapes of cauda epididymal sperm were analyzed (300-350 sperm/sample) with a Hamilton Thorn motility analyzer (HTM-2000, Hamilton Thorn Research, Danvers, MA). Epichlorohydrin did not affect the percentage of motile sperm at any time. However, transient changes in sperm velocity were found. On Day 1 postexposure mean progressive (straight line) and mean path (smoothed curvilinear) velocity were significantly decreased to 80 and 85% of control, respectively. The progressive velocities of sperm from both control and treated rats were normally distributed, indicating a general effect of epichlorohydrin on all sperm as opposed to a more severe effect on a specific sperm subpopulation. Sperm velocity was not significantly affected at later times. Other endpoints (testis and epididymis weights, testicular spermatid counts, and cauda epididymal sperm reserves) were unaltered by epichlorohydrin. Thus, inhaled epichlorohydrin at 100 ppm produced specific, transient decreases in rat sperm velocity. Furthermore, computer-assisted sperm analysis was able to detect these relatively subtle, toxicant-induced changes in rat sperm velocity, demonstrating the utility of this technology in reproductive toxicology studies. PMID- 2258023 TI - Chronic toxicity, oncogenic potential, and reproductive toxicity of p nitroaniline in rats. AB - Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of the sinusoidal macrophages or littoral cells of the liver and in the reticuloendothelial cells of the spleen. No treatment-related increase in tumor incidence was observed. In the reproduction study, no consistent pattern of effect from treatment between the F0 and F1 generation was seen in mating, pregnancy, or fertility indices. Thus, administration of PNA at levels which produced significant methemoglobinemia and low-level anemia in the rat and histological changes in the spleen produced no tumors or reproducible effects on reproductive performance. PMID- 2258024 TI - Hairless guinea pig bioassay model for vesicant vapor exposures. AB - Sulfur mustard (HD; 1,1'-thiobis[2-chloroethane]) induces fluid-filled blisters in man but not in conventional laboratory animals. An animal model is needed to emulate both cytotoxic (vesicant) and vascular (irritant) responses of human skin to HD exposures. An acceptable model must permit reproducible comparisons of uniformly graded and dose-related HD control responses with reduced responses that may follow antivesicant treatments. Hairless guinea pigs were evaluated by exposing six or eight dorsal skin sites 12 mm in diameter to similar HD vapor concentrations for graded intervals (1-16 min). HD vapor was delivered under occlusive caps holding 10 microliters of HD in filter paper located 5 mm above the skin. Four-minute exposures induced moderate erythema, slight edema, and microblisters in 1 of 39 sites. Eight-minute exposures induced severe erythema, moderate edema, and microblisters in 31 of 40 sites. Gross blistering was not seen after use of vapor cups, but damage to basal cells resembled lesions of vesicant injury in man. The hairless guinea pig model, with graded HD vapor exposures, provides acceptable comparisons of responses. Exposures of both 4- and 8-min durations were used to show the feasibility of using this model to bioassay antivesicant topical protectants. These methods may be useful for measurements of irritant and cytotoxic responses of skin to other toxic vapors. PMID- 2258025 TI - [Toward the medicine of the year 2000: what medicine?]. PMID- 2258026 TI - [Changes in the pattern of serum biliary acids and lipoprotein picture during therapy with biliary acids in cholesterol lithiasis]. AB - Several studies are present in the literature about the efficacy of medical treatment with biliary acid, orally administered, on the symptomatic gallstone patients. Both this drugs act, with different mechanisms, on the same pathophysiological pathway, represented by the supersaturated bile in cholesterol. Aim of the present investigation was to study the possible modifications of serum bile acids pattern and of lipoproteins in a large sample of gallstone patients under long-term treatment with biliary acids. One hundred and twelve patients with radiolucent gallstones entered the study; 54 received chenodeoxycholic acid (CDCA) and 58 ursodeoxycholic (UDCA) at dosage of 15 mg/kg/daily. Blood samples for determination of serum cholesterol, triglycerides, phospholipids, lipoproteins, total and fractionated biliary acids were collected from each subjects every three months for a mean "follow-up" of 24 months. The levels of serum cholesterol, triglycerides and phospholipids showed a mild decrease only in the patients under therapy with CDCA, while no modifications were detected using UDCA. The same was found for two other parameters, HDL cholesterol and lipoproteins, with both treatments during the overall period of follow-up. The biliary acids levels showed a significant increase only in the patients treated with CDCA, but no differences were found between "responders" and "non responders" to the therapy. PMID- 2258027 TI - [Systemic lupus erythematosus and pregnancy]. PMID- 2258028 TI - [Current treatment of bronchopulmonary infections]. PMID- 2258029 TI - [Clinical case. Congenital cardiopathy with pulmonary hyper-flow caused by interatrial defect of the "ostium secundum" type and paroxysmal atrial fibrillation]. PMID- 2258030 TI - [In memoriam: Luigi Belloni]. PMID- 2258031 TI - [Isolation of a spontaneous mutant of Escherichia coli superproducing proline and resistant to elevated concentrations of NaCl]. AB - We obtained a spontaneous mutant of Escherichia coli that was characterized by both proline superproduction and the resistance to osmotic stress. The selection of mutants was carried out among 2.5.10(5) clones survived upon plating strain SU1604 containing the sex factor F104, with a chromosome fragment carrying genes proB and proA, on solid modium with the proline analogue L-azetidine-2 carboxylate (AzT). The obtained mutant AztR clones were used as donors in replica crossing with a pro- recipient, followed by subsequent selection of AztR Pro+ exconjugants. Analysis of growth of 456 exconjugants in liquid minimal medium with NaCl at a concentration of 0.6 M helped to identify 9 mutants with increased salt tolerance, as compared with control. From these, we selected one mutant (denoted as SU1604/F'104S) which demonstrated the highest salt tolerance correlating with higher production of proline. Analysis of the mutant's properties suggests that it belongs to the group of Osm mutants. PMID- 2258032 TI - [Cloning and expression of Clostridium thermocellum F7 endoglucanase gene in gram negative bacteria]. AB - The endoglucanase gene of Clostridium thermocellum F7 was cloned in Escherichia coli cells using pKM4 vector. Both the physical mapping and analysis of the gene products in the E. coli mini-cells system suggest cloning of a new cel gene different from those described earlier. The activity of endoglucanase in E. coli cells is localized in the periplasm, which correlates with secretion of enzymes of this type in C. thermicellum. Apart from 2 major components with Mr 42.5 and 43 kDa, corresponding to mature protein forms, we observed the formation of minor products of various electrophoretic motilities. Cloning of the endoglucanase gene on bhr vector pBS954 controlled by its own regulatory signal yielded high level of the endoglucanase activity in the recombinant strains of Klebsiella pneumoniae, Serratia marcescens and Erwinia carotovora comparable with the level of the gene expression in E. coli cells. PMID- 2258033 TI - [tctN-mutation causing taillessness in mice heterozygous for gene T]. AB - Screening of wild male mice trapped in Turkmenistan (Middle Asia) revealed a mouse with a mutation causing strong increase in expressivity of T mutation (Brachyury). A novel mutation was designated tctN-t complex tail interaction Novosibirsk. Compound heterozygotes T/tctN have tailless of extremely short tailed phenotype. Homozygotes tctN/tctN were completely viable and fertile. It was shown that the novel mutation was closely linked to T locus. Further genetic analysis showed that the chromosome with tct had no properties of t haplotypes: no lethal factors or the factors influencing fertility and segregation of homologoues; there was no effect on recombination frequency in the proximal part of chromosome 17 in tctN/+mice. The problems of t haplotype evolution are discussed. PMID- 2258034 TI - [Repetitive DNA, chromosome polymorphism and speciation of gerbils]. AB - Restriction analysis of DNA and differential staining of chromosomes in three species of the genus Meriones: M. tristrami. M. meridianus. M. inguiculatus was carried out. High extent of homology of the genomes under study was found at the molecular and chromosomal levels. Speciation of M. tristrami followed by numerous fissions of metacentric chromosomes is assumed to be connected with appearance of the short BspRI sequence. Possible mechanisms of the mammal genome evolution are discussed. PMID- 2258035 TI - [Variability of the cytogenetic structure of Apodemus peninsula (Rodentia, Muridae) population from the West Sayans region]. AB - Karyological investigations of East-Asiatic mice (28 animals) from 5 catching points in the region of West Sayans revealed the presence of 1-12 B-chromosomes in these animals. Nearly all the mice had their individual variant of B chromosomes system, including combinations of two-shoulder-like chromosomes of different size (from 1 to 5), and also small acrocentric (from 0 to 1) and dot like B-chromosomes (from 0 to 9). Most frequent were the mice with 5 and 6 (21%) B-chromosomes. The catching points were 120 kilometers from each other, and clinical changes were observed between these points in the direction from the South to the North. PMID- 2258036 TI - [Revision of th distribution of chromosome aberrations induced by chemical mutagens using the BUDR label]. AB - Cell distribution was analysed with the help of the BrDU label for the number of chromosome aberrations and breaks induced by one-center (thiophosphamide and phosphamide) and two-center (dipine and fotrine) mutagens at the stage G0 in the Ist mitosis of human lymphocytes harvested at different times of culturing (from 56 to 96 h). The comparison was made between the type of aberration distribution in cells and the dependence of their frequency on the harvesting point for various mutagens. Poisson aberration distribution in cells for two-center mutagens was found to correspond to their constant frequency observed at different times of harvesting. On the other hand, for one-center mutagens, a geometrical distribution of chromosome breaks corresponded to an exponential decrease in their frequency in time. It is suggested that two-center chemical mutagens and ionizing radiation cause largely short-live damages which are realized into chromosome aberrations rather quickly (during one cell cycle). One center mutagens, however, cause such damages that the probability of their transformation into chromosome aberrations is decreasing rather slowly in time, under the exponential law, and their realization into chromosome aberrations can occur in subsequent cell cycle. PMID- 2258037 TI - [Chronogenetic control or the continuity of morphological organization during postnatal ontogenesis of man]. AB - Chronological peculiarities of genetic regulation of growth processes in morphological structures of postcranial skeleton ("body") and cranium ("head") were studied at different phases of peripubertal stage of boys ontogenesis. The component partitioning of the phenotype variance of individual scores of the structures considered revealed relative autonomy of chronogenetic systems controlling morphogenesis in the "body" and the "head". Succession of morphological organization is ensured by the stable level of correlation between morphological structures analysed. Raise in correlation is registered at the "critical" phase (13-14 years) which is connected with the "switching on" genetic programme of growth processes control in the adolescent period of human postnatal ontogenesis. PMID- 2258038 TI - [Distribution of C subtypes and other Tf variants in populations of the USSR]. AB - Serum samples from seventeen Caucasoids and Mongoloid populations of the USSR were tested for transferrin (Tf) subtypes. According to Tf patterns, the Caucasoids groups had high TfC1 frequency, whereas Mongoloids are characterized by increased frequency of TfC2 suballele. The following gene frequencies were observed: TfC1 - 0.8515, TfC2 - 0.1166, TfC3 - 0.0129, TfD - 0.0129, TfB - 0.0065 for Russians of Yegoryevsk town; TfC1 - 0.8663, TfC2 - 0.0930, TfC3 - 0.0233 for West-Pamirian populations of Khuf, those being for Pastkhuf 0.8476, 0.1159 and 0.0244, respectively. Mongoloid populations demonstrate following frequencies of five genes described (in the order shown above): 0.7870, 0.1620, 0.0232, 0.0139 for Kirghizes of East Pamir; 0.7963, 0.1805, 0.0050, 0.0182 for Buriats of Suduntui; 0.7647, 0.1985, 0.0074, 0.0221, 0.0037 and 0.0037 (gene TfDX) for Buriats of Sakhiurta, the frequencies of these genes being 0.7647, 0.1985, 0.0074, 0.021, 0.0037 and 0.0037 for Aginsky national district, Chita Region. The total sample of Buriats of Gakhan cluster (Ust-Ordyn national district) and Olkhon island of Irkutsk Region demonstrates following frequencies of genes (in the same order): 0.7876, 0.1962, 0.0012, 0.0057, 0.0082 and 0.7679 and 0.2321, respectively. In addition, a rare anodal variant designated tentatively TfC12Like was found among Pamir populations. The results obtained are compared with those reported for world populations. PMID- 2258039 TI - [Optimization of protective properties of interferons in human cells exposed to mutagens estimated by the DNA repair activity]. AB - Protective properties of human interferons against physical and chemical mutagens have been described earlier. This work was aimed at detecting an optimum of protective action of interferons in human fibroblasts using two criteria: the number of single-strand DNA breaks formed and the index of DNA repair synthesis. The protective ability of interferon was shown to be expressed starting after 4 h of cells' pretreatment and proceeding through 40 h in experiments with N-methyl-N nitro-N-nitrosoquanidin. The phenomenon of stimulation of DNA repair synthesis in human cells pretreated with interferon proceeded even after replating cells during 8 h in the experiments with UV irradiation. PMID- 2258040 TI - Allergens: standardization and impact of biotechnology--a review. AB - During the last 10 years, tremendous advances in the identification and characterization of allergens from a variety of substances have occurred. In this review, methods of allergen characterization and classification, as well as the effect of recent developments in biotechnology on allergen research, will be addressed. Prior to allergen isolation and characterization, adequate source material must first be identified. Most allergens that have been isolated are in the molecular weight range of 15,000 to 40,000 daltons and appear to be proteins or glycoproteins with acidic isoelectric points. A number of laboratory techniques have been shown to be extremely useful in identifying offending allergens and quantitating them in complex allergen extracts. Recently developed in vitro methods such as Western blotting, immunoprinting, and production of monoclonal antibodies to specific allergens will provide useful information for future analysis and standardization of allergen extracts. The effects of new technology on future developments in allergen characterization are far reaching. An important area of molecular biology that has only begun to be used in allergen research is the ability to clone and sequence DNA which codes for specific allergens. This facilitates the production of specific quantities of purified allergens provides material to determine their amino acid sequence, and allows production of standardized allergen preparations. Thus, it is conceivable that molecular biological approaches to allergen research will enable one to investigate the allergenic response at a molecular level and ultimately provide purified allergens in amounts sufficient for diagnosis and therapy. PMID- 2258041 TI - The mast cell: a comprehensive, updated review. AB - The mast cell has been suspected of playing an important clinical role for over a century. Improved techniques to isolate and purify homogeneous mast cell populations have made it easier to study mast cell activation, secretion, heterogeneity, and differentiation in several animal models including man. Despite the many laboratory accomplishments made which better characterize the mast cell, there is still a paucity of information that can be practically applied to clinical situations. This review will concentrate on events leading up to the recent advances made in specific areas of mast cell research. PMID- 2258042 TI - Effect of allergy medication on children's reading comprehension. AB - The impact of a very common over-the-counter antihistamine, chlorpheniramine, was measured in respect to the reading comprehension of 12 normal school-age children (5 boys and 7 girls) who had a history of allergic rhinitis. Each subject served as his/her own control, and a double-blind design was employed. Each child's parent was given two bottles of cherry syrup and told to administer the syrup in Bottle A for 3 days and then that in Bottle B for 3 days according to directions on the bottle. Parents and children did not know which bottle contained the medication. One of the two forms of a standardized reading comprehension test was administered at the end of each 3-day period in the allergist's office by a trained test administrator. Students were randomly assigned to the two conditions and to the form of the test administered. The mean reading comprehension scores of the drug and placebo drugs were 59 and 60, respectively, which were not significantly different. This study would indicate that common across-the-counter antihistamines should not adversely affect typical school activities such as reading comprehension if used appropriately. Even if some drowsiness or inattention may occur, children's cognitive functions are not affected sufficiently to disrupt learning. PMID- 2258043 TI - The effect of chlorpheniramine on asthma. AB - Patients with stable asthma can tolerate antihistamines without any significant deleterious effects both on a short- and a long-term basis. In addition, patients with steroid-dependent asthma appear to tolerate antihistamines without any significant deleterious effects. Therefore, oral chlorpheniramine does not appear to have ill effects on patients with asthma. Warning labels required by the FDA for antihistamine use in asthmatics are unnecessary. PMID- 2258044 TI - Psyllium anaphylaxis. AB - Allergic reactions from handling psyllium have been reported since 1970. Health professionals and workers in laxative-manufacturing plants are at greatest risk. Sensitized people are at risk of life-threatening anaphylactic reactions. Two illustrative cases are presented. The first is A 39-year-old female dialysis nurse with a 3-year history of nasal and eye symptoms from exposure to psyllium. She obtained an over-the-counter psyllium bulk laxative, took it for constipation and developed flushing, tachycardia, urticaria, angioedema, laryngeal edema, and lightheadedness. An epicutaneous skin test and radioallergosorbent test for psyllium were both strongly positive. The second is a 42-year-old female nurse with a history of asthma who had allergic nasal and eye symptoms while dispensing psyllium. She received a prescription for crystallized psyllium, took it by mouth, and developed immediate flushing, tachycardia, urticaria, and angioedema. With subsequent ingestion of psyllium she had, in addition, severe wheezing, lightheadedness, and loss of consciousness. A psyllium epicutaneous skin test was strongly positive. These patient reports illustrate the risk of severe allergic reactions in sensitized people. Ingestion by sensitized people, such as from a routine postoperative and postpartum order, is potentially dangerous. PMID- 2258045 TI - Absence of nasal priming as measured by rhinitis symptom scores of ragweed allergic patients during seasonal exposure to ragweed pollen. AB - A priming effect, increasing responsiveness of the nasal mucosa as measured by nasal patency or resistance, has been reported to occur after nasal challenge on successive days. Because it has been suggested that the priming effect may be of clinical importance, we have studied whether such an effect occurs during natural pollen exposure as measured by symptom-medication scores in 29 patients with ragweed rhinitis. By Wilcoxon's signed rank test, we compared the symptom medication scores of patients during two 7-day periods, one early in the season and one later, in which the weekly pollen count was approximately 250 grains/m3; we also compared an early and late period during which the weekly pollen count was approximately 500 grains/m3. There were no statistically significant differences in scores between early and late seasonal periods at the same pollen count. We conclude that the priming effect is not a clinically significant phenomenon during natural pollen exposure in allergic rhinitis patients. PMID- 2258046 TI - AAAI and ACAI should merge. PMID- 2258047 TI - Anaphylactoid reaction to aspirin (1902) PMID- 2258048 TI - Biography of Francis H. Chafee, M.D. December 12, 1903-April 24, 1990. PMID- 2258050 TI - Expression of cDNAs encoding barley alpha-amylase 1 and 2 in yeast and characterization of the secreted proteins. AB - Amylolytic strains of the yeast, Saccharomyces cerevisiae, were constructed by transformation with expression plasmids containing cDNAs encoding either AMY1 (clone E) or AMY2 (clone pM/C). The alpha-amylases were efficiently secreted into the culture medium directed by their own signal peptides. When clone E without its 5'-noncoding region was expressed from the yeast PGK promoter, AMY1 was produced as 1% of total cell protein and was thus the major protein secreted, whereas a similar construct derived from pM/C produced much less AMY2. This level is the highest reported for a plant protein secreted by yeast as mediated by the endogenous signal peptide. Production of AMY1 increased 25-fold when the 5' noncoding part of clone E which contains a 12-bp dG.dC homopolymer tail had been removed. Moreover, expression was one to two orders of magnitude higher when genes encoding AMY1 or AMY2 were inserted between promoter and terminator of the yeast PGK gene in comparison to expression directed from the ADC1 or GAL1 promoters. Recombinant AMY1 and AMY2 had the same Mr and N-terminal sequence as the corresponding barley malt enzymes. Furthermore, none of the enzymes were found to be N-glycosylated. Isoelectric focusing indicated that transformed yeast cells secreted one major form of AMY2 and four dominant forms of AMY1. One AMY1 form corresponded to one of the major forms found in malt while the others, having either low activity or unusually high pI, probably reflect inefficient/incorrect processing. Enzyme kinetic properties and pH activity dependence of recombinant AMY2 were essentially identical to those of malt AMY2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258049 TI - Heterologous gene expression by filamentous fungi: secretion of human interleukin 6 by Aspergillus nidulans. AB - Expression vectors for human interleukin-6 (hIL6) contain an expression cassette consisting of the Aspergillus niger glaA promoter and the Aspergillus nidulans argB terminator. The secretion signals were either those of glaA or that of the authentic hIL6 peptide. The constructs under study were introduced into A. nidulans and A. niger by means of cotransformation. No IL6 activity could be detected in the medium of a cotransformed A. niger strain, although transcripts corresponding with the IL6 cDNA were present. Evidence is presented that this apparent lack of IL6 expression is due to extracellular proteolytic activity. In the media of a cotransformed A. nidulans strain grown on starch, IL6 activity was detected by means of a bioassay. Up to 25 ng/ml of biologically active hIL6 could be secreted by A. nidulans transformed with the plasmid containing the mature hIL6-encoding gene fused to the glaA signal peptide nucleotide sequences. hIL6 of the expected 23-kDa size was also observed by Western-blot analysis of the medium. There was no evidence for glycosylation of the protein. PMID- 2258051 TI - Effect of CpG methylation on gene expression in transfected plant protoplasts. AB - Activity of the cat gene driven by the cauliflower mosaic virus 35S promoter has been assayed by transfecting petunia protoplasts with the pUC8CaMVCAT plasmid. In vitro methylation of this plasmid with M.HpaII (methylates C in CCGG sites) and M.HhaI (methylates GCGC sites) did not affect bacterial chloramphenicol acetyltransferase (CAT) activity. It should be noted, however, that no HpaII or HhaI sites are present in the promoter sequence. In contrast, in vitro methylation of the plasmid with the spiroplasma methylase M.SssI, which methylates all CpG sites, resulted in complete inhibition of CAT activity. The promoter sequence contains 16 CpG sites and 13 CpNpG sites that are known to be methylation sites in plant DNA. In the light of this fact, and considering the results of the experiments presented here, we conclude that methylation at all CpG sites leaving CpNpG sites unmethylated is sufficient to block gene activity in a plant cell. Methylation of CpNpG sites in plant cells may, therefore, play a role other than gene silencing. PMID- 2258052 TI - Expression and secretion of rice alpha-amylase by Saccharomyces cerevisiae. AB - We report the high level expression and secretion of rice alpha-amylase isozyme by Saccharomyces cerevisiae. Transcription of this gene was under control of the yeast enolase promoter. The synthesized protein had an approximate molecular size of 45 kDa and a pI of approx 4.7 to 5.0. The rice alpha-amylase signal peptide was recognized and efficiently processed by yeast and the active, glycosylated enzyme was secreted into the culture media. This enzyme was purified to homogeneity by affinity chromatography and its enzymatic properties were characterized. The Km and Vmax were found to be similar to those of alpha amylases from other organisms. The high level of secretion observed in these studies may be due to the unique features of the rice signal peptide and/or to the glycosylation of the recombinant enzyme. PMID- 2258053 TI - A binding protein (p82 protein) recognizes specifically the curved heterochromatic DNA in Artemia franciscana. AB - DNA bending has been suggested to play a role in the regulation of gene expression, initiation of DNA replication, site specific recombination and DNA packaging. In Artemia franciscana (Phillopoda anostraca) cells we have revealed that an AluI DNA family of repeats, 113-bp in length, is the major component of the constitutive heterochromatin found in the species. By analysis of cloned oligomeric (monomer to hexamer) heterochromatic fragments and electrophoretic experiments we verified that the repetitive DNA shows a stable curvature that confers a solenoidal geometry to the double helix. Using the cloned monomeric fragment, as molecular probe, we describe the detection in an A. franciscana cell extract of a protein of 82 kDa (p82) that preferentially binds to heterochromatic DNA. This protein, purified of the other DNA binding proteins present in the crude cell extract, shows a greater affinity with the tandem copies of the AluI DNA fragment than with the monomer sequence. The binding of p82 protein to heterochromatic DNA is also drastically reduced in the presence of the antibiotic distamycin A, suggesting a role of the DNA curvature in the formation of the nucleoproteic complex. PMID- 2258055 TI - Transcriptional control of the human Harvey ras proto-oncogene: role of multiple elements in the promoter region. AB - In the promoter region of the human c-Ha-ras1 gene, multiple elements for transcriptional control are dispersed. To examine the role of each element, we made a series of deletion mutants of this promoter region, including internal deletion mutants, and measured the promoter activities of these mutants. Any two of the four Sp1-binding sites upstream from the CCAAT-box element were sufficient for the maximal activity of the c-Ha-ras1 promoter. Either one of the two Sp1 binding sites downstream from the CACCC-box element was also necessary for the maximal promoter activity. Deletion of the CCAAT-box or CACCC-box elements reduced the level of transcription to 25% or 41% of that with the wild-type promoter. These results indicated that at least three Sp1-binding sites, and the CCAAT-box and CACCC-box elements contributed in concert to the activity of the human c-Ha-ras1 promoter. PMID- 2258054 TI - Simplified colorimetric analysis of polymerase chain reactions: detection of HIV sequences in AIDS patients. AB - We have previously described a colorimetric test, designated an amplified DNA assay (ADA), for specific segments of DNA amplified by polymerase chain reactions (PCRs), suited to diagnostic applications. This relied on binding the amplified DNA via a sequence in one oligodeoxyribonucleotide (oligo) to the DNA-binding protein GCN4 coated on the wells of a microtiter dish. Avidin-peroxidase was then bound to biotin at the 5' end of the other oligo and detected colorimetrically. Two successive PCRs with nested oligos were utilized. We describe here several modifications that greatly simplify the ADA. First, we bind the DNA to a glutathione S-transferase-GCN4 fused polypeptide (GST-GCN4) and avidin-peroxidase simultaneously, rather than successively. Second, we carry out the two successive PCRs in the one reaction mixture, using the thermal stabilities of oligos of differing lengths to separate the two reactions. Third, PCRs can be performed in the wells of a microtiter dish and the amplified DNA captured and detected via GST-GCN4 immobilized on beads attached to the lid of the microtiter dish. Hence it is only necessary to pipette the DNA sample once, and up to 96 samples can then be handled simultaneously. PMID- 2258056 TI - Murine ferritin heavy chain: isolation and characterization of a functional gene. AB - A mouse liver genomic library screened with a full-length cDNA encoding murine ferritin heavy chain (mFHC) [Torti et al., J. Biol. Chem. 263 (1988) 12638-12644] yielded a functional genomic clone mFHC. The genomic clone isolated included a region of approximately 3 kb containing four exons and three introns. Sequence comparisons of the mouse genomic clone with other genomic clones from rat, human and chicken showed a high degree of similarity among species in the coding regions. Introns and flanking sequences were less conserved. However, comparison of mFHC promoter elements with FHC genes from other species revealed common elements. Analysis of the genomic structure of FHC suggested the presence of pseudogenes. S1 nuclease analysis, however, confirmed that this mouse clone, when transfected into human MRC-5 fibroblasts, was transcribed, indicating that this clone contains an FHC functional gene. PMID- 2258057 TI - Organization of the gene family encoding mouse U3B RNA: role of gene conversions in its concerted evolution. AB - In mouse, U3B small nuclear RNA is encoded by a small family of four functional genes. Three of these genes have recently been identified, with two of them being located 5 kb apart, in the same orientation [Mazan and Bachellerie, J. Biol. Chem. 263 (1988) 19461-19467]. By analyzing a cosmid library of mouse genomic DNA we have isolated the fourth gene, U3B.4, which is located 12 kb downstream from the previously reported pair of linked genes, U3B.1 and U3B.2, in the same orientation. Its sequence analysis demonstrates that four mouse U3B genes have undergone a very efficient concerted evolution, with a perfect sequence identity not only over the entire RNA coding region but also over 254 bp of 5' flanking DNA which contain essential transcription signals. Moreover, in the regions which immediately flank the domain of perfect sequence identity, a patchwork of sequence similarities among the four genes is apparent, with a series of striking reversals in relationships between adjacent localized areas. This suggests that gene conversions have played a major role in the concerted evolution of the U3B gene family. A superimposition of conversion events, which probably occurred at distinct stages of rodent evolutions can be inferred. This has involved not only the three clustered copies, but also the remaining gene, U3B.3, the location of which relative to the cluster remains unknown. B1 repetitive elements are found at the boundaries of conversion domains, suggesting their possible role in control of the sequence homogenization process. PMID- 2258058 TI - Primary structure and assignment to chromosome 6 of three related rat genes encoding liver serine protease inhibitors. AB - Three closely related SPI genes which encode highly homologous proteins of the serine protease inhibitor family secreted by rat liver (SPI-1, SPI-2 and SPI-3), were isolated from genomic libraries and sequenced, totally (SPI-2) or partially (SPI-1 and SPI-3). These genes all map on rat chromosome 6. Each of them spans about 10 kb and contains five exons separated by four introns, located at equivalent positions. S1 mapping analysis indicated that initiation of transcription occurs at the same position (tsp) in each of the three genes. In vitro transcription experiments demonstrated the presence of promoter elements upstream from the putative tsp. Detailed analysis of 5'-flanking sequences in the three SPI revealed major differences. A high degree of identity (70%) was found within a 350-bp region preceding the 'cap' site, with the exception of a 42-bp spacer, which was only found in SPI-3. Upstream from that point, SPI-1 and SPI-2 sequences remain largely homologous over at least 1 kb but completely diverge from the corresponding sequence in SPI-3. This may, at least partly, account for the differential regulation of the three SPI observed during acute inflammation and upon hypophysectomy. PMID- 2258059 TI - Use of a selectable reporter for the isolation of mammalian regulatory genes. AB - A general method is described for isolating the genes encoding differentiation specific activators of transcription using genetic selection. Employing regulation of the prolactin encoding gene (PRL) as a model, we have shown that the hamster dihydrofolate reductase-encoding gene (dhfr) is an effective dominant selectable reporter in this methodology. The dhfr coding region was ligated to the rat PRL promoter, and the resultant construct was stably transfected into DHFR- Chinese hamster ovary (CHO) cells, where it had little or no activity. Transfection of these cells with plasmid DNA, containing the coding region of a pituitary-specific transcription factor (Pit-1/GHF-1) in a eukaryotic expression vector, resulted in transfectants in which activation of the chimeric construct, pPRLdhfr, had occurred, enabling these cells to be selected on the basis of their DHFR+ phenotype. Our results suggest that this strategy could be used to isolate unknown genes that regulate a variety of differentiated functions. PMID- 2258060 TI - Two nuclear proteins bind to the major positive element of the apolipoprotein B gene promoter. AB - The promoter of the apolipoprotein B-encoding gene (apoB) contains a number of regulatory elements, which together produce a high level of expression that is restricted to two tissues: liver and intestine. In this paper we have used the gel retardation and methylation interference assays to identify two nuclear proteins, LIT1 and LIT2, which bind to the major positive element (MPE) of the apoB promoter. LIT1 is large protein, estimated to be approx. 200 kDa by gel filtration, which binds to the apoB promoter between positions of -79 and -65 bp in relation to the transcription start point. Its binding site is identical to the region responsible for cell-specific transcriptional activation. However, whereas the MPE has no influence on expression from a heterologous promoter in the non-apoB-expressing HeLa cells, these cells still contain a DNA-binding activity indistinguishable from LIT1. LIT2 binds to the apoB promoter immediately downstream from the LIT1 site. It is present in nuclear extracts from the apoB expressing cell lines of hepatic (HepG2) and intestinal (CaCo-2) origin, but absent from HeLa cells. CCAAT/enhancer binding protein (C/EBP), expressed in bacteria, binds to the LIT2 site and produces a methylation interference pattern indistinguishable from that of LIT2. That C/EBP binds to and activates the apoB promoter in vivo, is shown by the increased chloramphenicol acetyltransferase activity observed when HepG2 cells, transfected with apoB-promoter-cat constructs, are cotransfected with a plasmid expressing c/ebp; an effect that depends on the presence in the apoB promoter of the LIT2 site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258061 TI - A cloned AluI-equivalent repetitive sequence that detects transfected hamster DNA. AB - An AluI-equivalent interspersed repetitive element showing 75% homology to a published consensus sequence, which is present at a level of 3 x 10(5) copies per hamster genome [Haynes et al., Mol. Cell. Biol. 1 (1981) 573-583], has been cloned into plasmid pUC8 as a tandem copy which can be readily excised, self ligated and labelled for use as a hybridisation probe. This probe successfully detects integrated hamster sequences in the DNA of transfected human cells [Arrand et al., Proc. Natl. Acad. Sci. USA 86 (1989) 6997-7001], whereas repetitive hamster DNA isolated as a C0t = 1 (fast reannealing) fraction fails to do so. Hamster DNA-containing clones in genomic libraries derived from hamster/human hybrids are also easily detected with this probe, thus facilitating the isolation of hamster genes which complement human gene defects. PMID- 2258062 TI - Effect of propionyl-L-carnitine on rat spinal cord ischaemia and post-ischaemic reperfusion injury. AB - In this study we have examined the effect of propionyl-L-carnitine (PC) on rat spinal cord ischaemia and post-ischaemic reperfusion injury by evaluating two lipid peroxidation indices, thiobarbituric acid reactive substances (TBARS) and diene conjugation, before and after the addition of an ADP-Fe+2 complex to spinal cord homogenates. Aerobic, ischaemic, and post ischaemic reperfusion rat spinal cord homogenates from PC treated and untreated animals did not show any statistically significant difference in their TBARS and conjugated diene content. The addition of the ADP-Fe+2 complex to these homogenates resulted in an increased production of both the lipid peroxidation indices, though the magnitude of such formation was related to the type of experimental intervention. The post ischaemic reperfusion samples of untreated rats showed the highest TBARS and conjugated diene content, while ischaemic samples in either treated and untreated rats did not show any statistically significant difference with respect to the aerobic samples. The post-ischaemic reperfusion samples of treated rats showed a statistically significant decrease of TBARS and conjugated diene production in comparison to the untreated samples. In addition, PC was also able to partially inhibit TBARS and conjugated diene formation in linoleic acid micelles exposed to hemoglobin, though it did not protect albumin fragmentation from the irradiation of water with an X-ray source. PMID- 2258063 TI - A randomized trial of cyclophosphamide, doxorubicin, and cisplatin with or without bacillus Calmette-Guerin in patients with suboptimal stage III and IV ovarian cancer: a Gynecologic Oncology Group study. AB - Four hundred and eleven evaluable patients with suboptimal (greater than 1 cm residual) stage III and IV and recurrent ovarian cancer after surgical exploration and tumor debulking were prospectively randomized to receive cyclophosphamide, doxorubicin, and cisplatin (CAP) with or without bacillus Calmette-Guerin (BCG). Therapy was planned for eight courses with the BCG to be given by the sacrification technique on Days 8 and 15 of each course. The addition of BCG did not improve response rate, progression-free interval (PFI), or survival. In a multivariate analysis prognostic factors significantly favorable for survival include nonmeasurable disease and young age. Those patients having tumor with a mucinous histology had poorer survival and PFI than patients with tumors composed of other cell types. PMID- 2258064 TI - A cohort analysis of cervical cancer in Israeli Jewish women. AB - The incidence of squamous cell cervical cancer was studied in Jewish Israeli women between 1961 and 1981. The 1052 cases and the 27,832,272 women-years of observation were divided according to continent-of-origin, year-of-birth, and immigration-wave cohorts. Age-adjusted odds ratios were calculated for each cohort and compared. The incidence of cervical cancer was shown to have changed according to cohort year of birth, most significantly in women born in Europe and America. The highest risk in this group was seen in women born in 1891-1895 and 1941-1945 and the lowest in women born between 1926 and 1935. A high risk was also observed in all cohorts of North African women. There was a sharp rise in risk for women of all origins born after 1940. Immigration to Israel at a younger age was correlated with reduced risk for cervical cancer. It has been shown that epidemics of sexually transmitted diseases (STDs) are followed in time by epidemics of cervical cancer. Since there was an epidemic of STDs in Israel between 1967 and 1970, our results also suggest that there is a rise in the risk for cervical cancer in women who were sexually active during the epidemic of STDs. Because of the low rates for cervical cancer traditionally observed in Israeli women, routine screening was not done in Israel in the past. Should the relative risk for cervical cancer in women exposed during the 1967-1970 epidemic continue to be high, screening may prove worthwhile. PMID- 2258065 TI - Cisplatin-based chemotherapy for stage II ovarian adenocarcinoma: a preliminary report. AB - We have performed three sequential trials in patients with FIGO stage II ovarian cancer in an attempt to improve long-term survival. The first trial utilized whole-abdomen radiation and a pelvic boost and the second study utilized pelvic radiation plus melphalan chemotherapy. These trials resulted in estimated 5-year survivals of 40 and 50%, respectively (Gynecol. Oncol. 23, 168-175, 1986). In the current study, 20 patients were treated with 6 months of adjuvant cisplatin-based chemotherapy. The estimated progression-free survival was only 45%. However, by tailoring salvage therapy to the findings at second-look laparotomy, the estimated 5-year survival was 77%. Notwithstanding the latter result of 77%, improved therapy is still required for the relatively rare patient who has stage II ovarian cancer. PMID- 2258066 TI - Body fat patterning in women with endometrial cancer. AB - It has long been known that the risks of some cancers, including endometrial, are associated with obesity. Recent evidence suggests that body fat distribution patterns also affect the risk of developing some diseases. A question that remains is whether cancers are associated with specific distributions of body fat. In this study, women with endometrial cancer were compared to community controls of similar age and race. Participants were interviewed and then measured to determine fat distribution patterns defined by the waist-to-hip circumference ratio. Women with upper body fat distribution had a 3.2-fold (95% confidence limits 1.2, 8.9) higher risk of endometrial cancer than women with lower body fat distribution even with correction for age, parity, and smoking. Obese women with an upper body fat pattern had a 5.8-fold (confidence limits 1.7, 19.9) higher risk of endometrial cancer than nonobese/lower body fat patterned women. Obese women who never smoked had a 3.3-fold statistically significant higher risk of endometrial cancer than nonobese women who never smoked. Current smokers had lower risks than their nonsmoking counterparts. The 3-fold increased risk of endometrial cancer associated with upper body fat did not disappear with adjustment for obesity and smoking. PMID- 2258067 TI - Pure primary osteosarcoma of the ovary presenting as an extensively calcified adnexal mass: a case report and review of the literature. AB - A case of primary ovarian osteosarcoma is reported with a review of the literature. A perimenopausal woman presented with a calcific adnexal mass seen on abdominal radiography, surgical exploration revealed no gross evidence of metastatic disease. Adjuvant chemotherapy was administered due to the reported aggressiveness of this rare tumor. Following eight courses of cisplatin doxorubicin combination chemotherapy, the patient is without evidence of disease. A differential diagnosis for extensively calcified adnexal masses is provided. Additionally, a rationale for adjuvant chemotherapy is discussed. PMID- 2258068 TI - Primary resection of vaginal metastases with the Cavitron ultrasonic surgical aspirator in stage III endometrial carcinoma. AB - Use of the Cavitron ultrasound surgical aspirator (CUSA) to resect vaginal metastases in clinical stage III endometrial carcinoma is reported in two cases. The CUSA allowed cytoreduction before pelvic radiation therapy without additional morbidity. PMID- 2258069 TI - Serous papillary carcinoma of the endometrium: a histopathological study of 22 cases. AB - In a histological review of all 1985 cases of endometrial carcinoma in Norway diagnosed in the period 1970 through 1977, 22 patients (1.1%) with serous papillary carcinoma (ESPC) were identified. Mean age at diagnosis was 72 years, which was significantly higher than for patients with ordinary adenocarcinoma. All patients were followed at least 10 years. The crude 5- and 10-year survival rates were 27 and 14%. Only three patients survived longer than 10 years and all of these had had stage I tumors. In 19 available curettage specimens ESPC could be identified in 18. This could have implications regarding choice of therapy because this subtype of endometrial carcinoma is very aggressive. It is most often found in elderly women. PMID- 2258070 TI - Prognostic value of pathologic features and DNA analysis in endometrial carcinoma. AB - In a series of 38 nonmetastasizing and 29 metastasizing endometrial cancers, histologic subtype, aneuploidy, nuclear grade, and depth of myometrial invasion were the features most distinctly separating these two groups of patients. The most important factor was histologic type: papillary, papillary serous, adenosquamous, clear cell, and diffusely infiltrating carcinomas were strongly correlated with metastasis using chi square analysis. Nuclear grade 3 and deep myometrial invasion were similar to each other in sensitivity and predictive value, and both were also strongly correlated with metastatic risk. Aneuploidy, also correlated with metastasis, was similar to nuclear grade 3 and deep myometrial invasion in predictive value but was more sensitive. DNA analysis appeared to be most useful when histologic studies were inconclusive in assigning a high degree of risk. Twice as many aneuploid carcinomas having nuclear grade 2 (intermediate risk) morphology proved to be metastatic. A similar relationship was found with deep myometrial invasion. A quantitative correlation between the DNA index and the risk of metastasis was found; a DNA index above 1.5 was a strong attribute of the metastatic group. PMID- 2258071 TI - Use of the inferior vena cava clip in patients at high risk for pulmonary embolism. AB - Sixteen gynecologic oncology patients at high risk of developing a postoperative pulmonary embolism underwent prophylactic clipping of the inferior vena cava during laparotomy for tumor resection. All patients had a prior history of deep venous thrombosis or pulmonary embolism or had an active deep venous thrombosis at the time of their surgery. Additionally, this group of 16 patients was characterized as being at high risk for recurrent thrombosis in the postoperative period based on traditional risk factors that are representative of most gynecologic oncology patients. The Adams-DeWeese or Moretz clip was used in this series. There were no pulmonary emboli in our 16 patients in the postoperative period or during follow-up. There were no signs of venous stasis attributable to clip placement. The procedure was quick, simple, and complication free and the external clip has the advantage of maintaining effectiveness throughout the patient's lifetime. Prophylactic clipping of the inferior vena cava at the time of laparotomy in patients at an increased risk of thrombosis deserves further study. PMID- 2258072 TI - Prognostic significance of tumor ploidy in patients with advanced ovarian carcinoma. AB - Fresh tumor specimens obtained from 53 consecutive patients with FIGO Stage III ovarian carcinoma were analyzed by flow cytometry. All patients were treated by a standard protocol: maximal tumor excision and cisplatin/cyclophosphamide/adriamycin chemotherapy, and followed-up for at least 24 months. Thirty-two percent of tumors were diploid (DNA index = 1.00) and 68% aneuploid (DNA index greater than 1.00), with more aneuploid tumors being associated with larger residual tumor and poor cellular differentiation. Patients with diploid tumors were found to survive significantly better than those with aneuploid tumors, in terms of survival rate (65% versus 31%), median survival time (33 months versus 13 months), and mean disease-free interval (17.8 months versus 8.2 months). The influence of the amount of residual tumor after primary surgery on survival was only significant in patients with diploid tumors. Our results support previous findings that tumor ploidy is an important prognostic indicator in ovarian cancer. We found aneuploidy to be associated with a poorer clinical outcome in Stage III disease, regardless of the amount of residual tumor after primary surgery and the degree of cellular differentiation. PMID- 2258073 TI - Phase I study of intraperitoneal carboplatin as adjuvant therapy in early ovarian cancer. AB - Early stage poor-risk ovarian cancer patients are at considerable risk for recurrent disease. Adjuvant radio- or chemotherapy has been found to improve disease-free and overall survival. Carboplatin, a second generation platinum, is documented comparable in efficacy to cisplatin in patients with advanced ovarian cancer. The toxicity profile is different from that of cisplatin. Dose-limiting toxicity is myelosuppression. The incidence and grade of renal and neurological toxicity is much lower compared with cisplatin, as is nausea and vomiting. Carboplatin given intraperitoneally (ip) is shown to have a favorable theoretical therapeutic advantage compared with iv administration since the peak peritoneal cavity/peak plasma concentration ratio is 18. Patients with early stage ovarian cancer seem suitable for carboplatin ip treatment. The study was designed to find the maximal tolerated dose (MTD). Three new patients were given two courses at each dose level. The MTD found was confirmed with further patients. Carboplatin was given in 2 liters of glucose via a subcutaneous implantable port without removal of fluid from the cavity. The starting dose was 300 mg/m2. Dose-limiting toxicity was thrombocytopenia and leukopenia. Leukocyte and platelet counts were reconstituted within 28 days in all cases. One case of severe but transient nephrotoxicity was observed. MTD was determined to 500 mg/m2. PMID- 2258074 TI - Advanced ovarian cancer: long-term results following chemotherapy and second-look laparotomy. AB - Thirty patients who showed a complete clinical response to cis-platinum containing combination chemotherapy underwent second-look laparotomy. Seventeen patients (56.7%) achieved a pathologically confirmed complete remission as documented by a negative second-look laparotomy. After a minimum follow-up of 60 months, 6 of 17 patients developed recurrent disease and subsequently died. Due to the occurrence of late relapse in these negative second-look patients routine second-look laparotomy to confirm pathological response cannot be justified. Ten of thirty patients underwent secondary cytoreductive surgery at second-look operation. All ten patients had suboptimal initial debulking surgery. Five of these ten patients (50%) survived 4 years. Secondary cytoreductive surgery may improve survival in patients who undergo suboptimal initial debulking surgery. PMID- 2258075 TI - Analysis of 138 consecutive ovarian cancer patients: incidence and characteristics of familial cases. AB - Eight families with two or more first-degree relatives affected with ovarian carcinoma were identified among a series of 138 consecutive ovarian cancer patients. History of breast cancer was reported in six of the eight families. Five of 19 patients with familial cancer developed ovarian cancer as a second primary tumor following breast carcinoma, whereas only 6/130 sporadic cases had a previous history of breast cancer. No significant difference was detected in clinical and pathological features between sporadic and familial cases. However, in three high-risk families ovarian cancer tended to develop at a younger age compared with other familial cases and with sporadic occurrences, and nulliparity was less frequent in the familial group. These observations emphasize the need to take into account multiple factors-in addition to positive family history-for the evaluation of genetic predisposition to ovarian carcinoma. PMID- 2258076 TI - Nucleolar organizer regions in malignant transformation of uterine cervix. AB - Nucleolar organizer regions (NORs) in 70 cases of precancerous and cancerous lesions of the uterine cervix were investigated. The greater the degree of dysplasia, the higher the mean number of silver-stained NOR (Ag-NOR) dots (mild dysplasia, 2.2; moderate dysplasia, 2.5; severe dysplasia, 3.1). The mean number of dots in moderate or severe dysplasia was significantly higher than that in normal squamous epithelial cells. The mean numbers of dots in carcinoma in situ (CIS) and invasive carcinoma were 3.8 and 3.7, respectively, and were significantly higher than those in normal squamous epithelial cells, mild dysplasia, moderate dysplasia, and severe dysplasia. The mean number of Ag-NOR dots in the cases of mild dysplasia that progressed to CIS was 2.7, which was significantly higher than that in the cases that regressed. In precancerous lesions, the correlation coefficient between the mean number of Ag-NOR dots and the mitotic index was 0.552 (p less than 0.01), whereas no correlation was noted between these measurements in CIS and invasive carcinoma. In conclusion, the number of Ag-NOR dots is a good marker to detect cell proliferation in precancerous lesions and their malignant tendency. PMID- 2258077 TI - Clear cell carcinoma arising in extraovarian endometriosis: report of three cases and review of the literature. AB - The literature on malignancy arising in extraovarian endometriosis comprises only three cases of clear cell carcinoma. We wish to report the clinical features and pathologic findings of an additional three cases. The first concerns a 39-year old oriental pregnant woman who presented with a large intraluminal obstructing lesion of the sigmoid colon, the second case deals with an abdominal wall mass that appeared in a cesarean section scar of a 45-year-old black woman, and the third case describes an ulcerating lesion of the perineum and the buttock in a 43 year-old white woman with a long history of endometriosis in an episiotomy scar. Our observations support the notion that clear cell carcinoma arising in extraovarian endometriosis behaves differently from its counterpart in ovarian endometriosis, but more in line with clear cell carcinoma of the endometrium. PMID- 2258078 TI - Depth of myometrial invasion in endometrial cancer: preoperative assessment by transvaginal ultrasonography. AB - Twenty-five patients with cancer of the uterus underwent transvaginal sonography (TVS) to assess depth of myometrial invasion. All scans were performed with a 5.0 MHz curvilinear array probe (Toshiba, Inc., Tustin, CA) within 1 week of hysterectomy. In 21 cases (84%) sonography correctly predicted the depth of invasion (within 15% of actual). Only one of three cases with cervical involvement was detected. Transvaginal sonography can accurately detect depth of myometrial invasion and is well suited as a screening test to detect high-risk patients for consultation or referral. PMID- 2258079 TI - Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin. AB - Combination laser conization was performed in 469 patients for the treatment of cervical intraepithelial neoplasia (CIN). In 58 cases (12.4%), CIN was located in the margins of the cone. Fifty-one patients with involvement of the margins were evaluated by cytologic examination, using the Ayre spatula and the Cytobrush, and by cervical biopsy and endocervical curettage (ECC). In six cases, the histologic evaluation was positive, and in three of these cases, the cytology was positive too. Hysterectomy was performed in five cases, but in only one case was a significant lesion demonstrated in the uterus. These results justify expectant, conservative management of patients treated with combination laser conization. Follow-up based on colposcopy and cytology seems sufficient. PMID- 2258080 TI - A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. AB - Forty-one eligible patients with metastatic or recurrent carcinoma of the uterine cervix received 149 courses of carboplatin. The drug was administered at a starting dosage of 400 mg/m2 IV every 28 days. The overall response rate was 15% (two complete responses, four partial responses; 95% confidence interval 6-29%) and response durations were 2.0, 2.0, 2.5 +, 2.5+, 5.25 +, and 6.75 months. The major toxic effects included nausea and vomiting in 48% of courses, anemia in 47%, leukopenia in 38%, and thrombocytopenia in 22%. The activity of carboplatin against advanced cervical cancer is modest and similar to the activity of cisplatin alone. However, the toxicity profile of carboplatin is substantially better than that of cisplatin and warrants exploration of this agent against cervix cancer in more aggressive regimens or in combination with other agents. PMID- 2258082 TI - Papillary carcinomas of the endometrium. AB - A retrospective study of patients with papillary endometrial carcinomas was performed. Of 761 patients with endometrial carcinomas treated at the Royal Brisbane Hospital between 1982 and 1989, 19 (2.4%) had papillary endometrial carcinoma (PEC) and 21 (2.8%) had papillary serous endometrial carcinoma (SPEC). Patients were similar in age and parity but survival was significantly poorer in cases of SPEC than PEC. Patients with SPEC had a 47% 3-year survival with surgically documented localized disease. Recurrences were mainly outside the field of adjuvant radiotherapy. It thus appears that local treatment is not sufficient and some form of systemic treatment is required. PMID- 2258081 TI - Endometrioid carcinoma of the ovary: retrospective review of 145 cases. AB - From 1967 through December 1987, 145 patients with endometrioid carcinoma of the ovary were treated at the University of Texas M. D. Anderson Cancer Center. Thirty-eight patients (26.2%) had stage I disease, 28 (19.3%) stage II, 60 (41.4%) stage III, and 11 (7.6%) stage IV; 8 patients (5.5%) were unstaged. Grade 2 or 3 histology was seen in 119 patients (82.1%). In addition to surgical therapy, 128 patients underwent chemotherapy, including single-agent therapy, noncisplatin combination therapy, and cisplatin-based therapy. No statistically significant improvement in median survival was noted among these three chemotherapy groups for stages II, III, and IV (P = 0.22). A significant improvement in median survival was noted for those patients who achieved a complete clinical response, regardless of type of chemotherapy (96 or more months for single-agent therapy, P = 0.001; 31.5 months for noncisplatin combination therapy, P = 0.016; and 85 months for cisplatin-based therapy, P = 0.0001). Synchronous ovarian and uterine malignancies were seen in 18 patients (12.4%). No difference in survival was seen for patients with endometriosis (P = 0.13) or endometrial cancer (P = 0.09) when compared with those who did not have these histologic findings. PMID- 2258083 TI - Tumor markers CA 125, carcinoembryonic antigen and tumor-associated trypsin inhibitor in patients with cervical adenocarcinoma. AB - Tumor markers CA 125, carcinoembryonic antigen (CEA) and tumor-associated trypsin inhibitor (TATI) were studied in 42 patients with cervical adenocarcinoma. Pretreatment levels of CA 125 were elevated in 73% of 33 patients, CEA in 48% of 27 patients, serum TATI in 23% of 22 patients, and urine TATI in 38% of 26 patients. Elevated CA 125 levels were associated with histological grade (P = 0.002), and elevated CEA levels with the presence of lymph node metastases (P = 0.008), respectively. No associations were found between elevated tumor marker levels and stage, or tumor size. Serum CA 125 levels increased in 71% of the patients with progressive disease, CEA levels in 36%, serum TATI levels in 46%, and urine TATI levels in 20% of the patients. In all patients with regressive disease the tumor marker levels decreased or stayed unchanged. Regression of the disease was significantly correlated (P less than 0.05) with stage, histological grade, tumor size, and nodal status. The results suggest that CA 125 and, to a lesser extent, CEA and TATI are useful in the follow-up of patients with cervical adenocarcinoma. PMID- 2258084 TI - Uterine sarcoma: steroid receptors and response to hormonal therapy. AB - Seventy-three patients with uterine sarcomas were treated between 1976 and 1987. Steroid receptors were analyzed in 60 cases; 48% were estrogen receptor (ER) positive, and 30% progesterone receptor (PR) positive. Only 1 of 28 patients with residual or recurrent disease showed a response to hormonal therapy. Neither receptor status of the primary tumor nor use of adjuvant hormonal therapy affected survival. PMID- 2258085 TI - Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium. AB - In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging. PMID- 2258086 TI - A successful term pregnancy following the systemic and intraperitoneal administration of cisplatin chemotherapy. AB - The advent of successful chemotherapy has improved the prognosis and long-term disease-free survival for many patients with a variety of malignancies. Preservation of reproductive function in female patients is now possible with conservative surgery in certain selected malignancies. Successful pregnancies following chemotherapy or ovarian cancer have been reported. This is the first reported case of a term pregnancy following the systemic and intraperitoneal administration of cisplatin chemotherapy in the treatment of ovarian cancer. PMID- 2258087 TI - Leiomyosarcoma arising in a lipoleiomyoma. AB - A leiomyosarcoma arising in a uterine lipoleiomyoma is described in a 70-year-old woman. The tumor measured 11 cm and was located in the corpus uteri. It was composed of a mixture of firm, pale tan, whorled tissue and soft, white or hemorrhagic areas. Histologically, the firm tissue was a mixture of bland smooth muscle, fat and fibrous tissue, whereas the soft areas showed a malignant spindle cell tumor with smooth muscle differentiation. Pure sarcoma similar to the malignant portion of the lipoleiomyoma had metastasized to the vaginal wall. PMID- 2258088 TI - [Aqueous drainage implants in glaucoma]. AB - The use of implants to drain aqueous from the anterior chamber to a posterior collecting reservoir is an important additional option in the treatment of advanced refractory glaucoma. In the past decade, many problems and complications associated with drainage implants have been solved by modifications in implant design and surgical technique. These include: entry of the tube into an equatorial collecting device, increased surface area of the collecting reservoir, use of a needle track to insert the tube into the anterior chamber, suturing a donor scleral patch to cover the tube, intracameral injection of hyaluronic acid (Healon), ligation of the tube with a temporary suture, and antifibrotic medical therapy. The adoption of some or all of these modifications in recent years has clearly resulted in fewer complications and better long-term control of intraocular pressure. PMID- 2258089 TI - [Decision-making in the psychiatric emergency room]. AB - The decision-making process in the emergency room is evaluated in accordance with the literature and our growing experience. Research until now emphasized correlations among different variables, demographic, clinical, and the individuality of clinicians and systems, on the decision to admit. Many subtle and difficult-to-describe variables were not considered in most of the studies; we have tried to describe some of them. There is a place for clinical research in the decision-making process. PMID- 2258090 TI - [Characteristics of smoking and differentiations in smoking habits]. AB - Sociodemographic and behavioral characteristics were analyzed in 221 men and 126 women, aged 21-80 years, in a family medical clinic. The overall smoking rate was 42.3% (55% for men and 30.1% for women). The proportion of smokers was significantly higher than in the findings of earlier surveys in Israel from 1983 1986. Among those who did not complete high school, there was a tendency to an increase in the proportion of smokers with increase in education (p less than 0.001). But among those with higher education, the smoking rate was the lowest (p less than 0.001). The highest smoking rate was among those born in Israel, lower in those born in Asia-Africa and lowest in those born in Europe. Women had smoked for fewer years than men (p less than 0.01). There was a significantly higher proportion of men and women who had started smoking at ages 18-20 years. This age group, liable to compulsory service, represents a special risk group for starting to smoke. Men smoked significantly more cigarettes/day than women (p less than 0.001): 47.9% of men and 16.8% of women were heavy smokers. Since heavy smokers have more difficulty in stopping, they represent a risk group for the development of smoking-related diseases. The number of attempts at quitting was the same for men and for women, but the periods of smoking cessation were longer in men. We recommend that the civilian and military medical-health services set up an overall educational field program for soldiers and for family physicians.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258091 TI - [Seasonal variation in duodenal ulcer disease in the Upper Galilee]. AB - Active duodenal ulcer disease was diagnosed in 179 of 748 patients presenting with onset of symptoms of the peptic syndrome in the course of 3 years. The diagnosis was made on the basis of either endoscopy or X-ray. The highest average annual incidence was in kibbutzim and the lowest in moshavim (98.9 and 49.2 new cases/year/100,000, respectively). A peak in the diagnosis of new cases of active duodenal ulcer was demonstrated in November, December and January, compared with an equal distribution among other months. There was a diagnostic peak in the winter, and a seasonal decrease in the fall (56 +/- 4 vs 38 +/- 4, M +/- SE, respectively). These findings were statistically significant when proportions of total visits to the Gastroenterology Clinic were compared (Z = 1.976; p less than 0.05). PMID- 2258092 TI - [Psoriatic arthritis and human immunodeficiency virus infection]. AB - Recent reports have suggested an association between psoriasis, psoriatic arthritis and human immunodeficiency virus infection (HIV). However, few cases of coincidental occurrence of HIV infection and psoriatic arthritis have been described. We present another patient with psoriasis who developed a sudden flare up of this skin disease associated with onset of psoriatic arthritis, during the course of HIV infection. Psoriatic arthritis should be added to the expanding spectrum of musculoskeletal manifestations of HIV infection. PMID- 2258093 TI - [Reflex sympathetic dystrophy in children]. AB - Reflex sympathetic dystrophy (RSD) in children is a clinical syndrome characterized by pain in the extremities associated with hyperesthesia and vasomotor changes. The symptoms frequently result in serious impairment in function of the involved extremity. Treatment should be initiated as soon as possible and include intensive physical therapy; analgesics and transcutaneous nerve stimulation can be added as needed. Compared with the adult, childhood RSD is of unknown etiology and has a better prognosis. RSD has attracted little attention in clinical pediatric practice and in pediatric textbooks and the literature, so the diagnosis may be missed. We report 2 girls with RSD, aged 12 and 15 years, respectively, who were successfully treated with conservative measures; both recovered, with no sequelae. PMID- 2258094 TI - [BCG-induced axillary lymph-adenitis in the adult]. AB - Axillary lymphadenopathy is very common, with a wide and well-known differential diagnosis. We present for the first time in the contemporary English medical literature the case of a 50-year-old woman with unilateral axillary lymph node enlargement due to BCG injection 2 months earlier. The difficulty in diagnosis is because BCG inoculation is rare in adults, and the latent period is long, up to 8 months. This was the cause of initial misdiagnosis. We conclude that unilateral axillary lymphadenopathy in adults travelling to third-world countries, should raise the question of BCG-induced lymphadenopathy. PMID- 2258095 TI - [Bedtime administration of metformin may reduce insulin requirements]. AB - The administration of metformin, as glucophage retard, at bedtime instead of supper time may improve diabetes control by reducing morning hyperglycemia. This modification of glucophage treatment was tried in 3 groups of diabetic patients: I. those with secondary failure of routine treatment with sulfonylurea (SU) and glucophage; II. those with combined SU and bedtime insulin; III. Type 1 patients with early morning hypoglycemia. The first 3 months of observation in 258 patients showed that 136 (52.7%) reacted very well to the change. In Group I the addition of insulin to SU could be postponed. In Group II, night insulin could be reduced or eliminated. In Group III, evening or night insulin could be reduced by up to 70%. There was no early morning hypoglycemia nor morning hyperglycemia. The success rate in the 2 Type 2 groups was better (72% and 60%) than in the Type 1 group (34%). 30 patients (11.6%) had to stop the treatment because of side effects of the glucophage (mainly diarrhea or nausea). So far, we have found no clinical signs that might indicate which patients might benefit from this modification of treatment. A fasting blood sugar done within 2-3 days after the change in treatment may immediately indicate whether the new treatment is effective. PMID- 2258097 TI - [Liposuction present status 1990]. PMID- 2258096 TI - [The high risk pregnancy unit]. AB - During the past 30 years there has been great progress in perinatology. However, perinatal mortality has remained relatively high. To reduce perinatal mortality and morbidity, high risk pregnancy units have been established throughout the world. Our unit was established in 1976 for women with diseases complicating pregnancy, and in whom evaluation of fetal respiratory and metabolic function is indicated. The cesarean section rate during these 12 years was 33%. There was no maternal mortality. The intrauterine fetal death rate was 10.3 per 1,000 (very low for this unique population) and the corrected perinatal mortality was 3.4 per 1,000. The monitoring and treatment protocols, developed and applied in this unit, resulted in a significant decrease in fetal morbidity and mortality. These dramatically improved results demonstrate and justify the need for high risk pregnancy units. PMID- 2258098 TI - [Transrectal electroejaculation]. PMID- 2258099 TI - [Attention deficit disorder]. PMID- 2258100 TI - [The pregnant woman, car accidents and the seat belt]. PMID- 2258101 TI - [Relationship between cigarette smoking and epithelial cancer of the uterine cervix]. PMID- 2258102 TI - [Penicillin allergy--is the risk over?]. PMID- 2258104 TI - [The school physician and his work?]. PMID- 2258103 TI - [Allergic reactions to measles, mumps and rubella vaccine in children with egg protein allergy]. PMID- 2258105 TI - [Medical care for adolescents--a combined hospital and community service]. PMID- 2258106 TI - [Andreas Vesalius' pilgrimage to Jerusalem]. PMID- 2258107 TI - [Diabetes in the elderly]. PMID- 2258108 TI - [Ultrasonographic diagnosis of amniotic band syndrome in pregnancy]. AB - The amniotic band syndrome comprises a heterogenous group of congenital deformities which originate from rupture of the amnion during the early stages of fetal development. The diagnosis of the syndrome in the newborn is difficult because of the wide spectrum of anomalies, and its resemblance to other genetic or developmental deformities. The prenatal diagnosis of the syndrome is possible when there is ultrasonographic demonstration of multiple, nonembryological anomalies, with or without visualization of amniotic bands floating in the amniotic fluid. We recently diagnosed prenatally 3 fetuses affected by this condition. 2 were members of different twin pregnancies who presented with severe multiple malformations, and the other was a singleton with a big facial cleft and Pierre-Robin syndrome. PMID- 2258109 TI - [Breast biopsy of nonpalpable lesions after mammography-guided wire localization]. AB - Mammography is used increasingly for diagnosis and screening. Its advantage is its ability to discover very small and often nonpalpable mammary lesions. While its sensitivity in detecting pathological changes in the breast is high, differentiation between benign and malignant lesions is less precise, so biopsy is necessary. To ensure removal of the entire lesion with minimal damage to breast tissue, precise localization is mandatory. The accepted technique is the needle-wire method. 39 of 167 biopsies guided by mammography performed during 3 years for nonpalpable lesions detected by mammography were malignant. In 24 of them the histological diagnosis was atypical epithelial proliferation, considered a transition to carcinoma. PMID- 2258111 TI - [Fine needle aspiration cytology for orbital lesions]. AB - Cytological examination of fine needle aspiration (FNA) material from orbital lesions is a simple but reliable procedure. FNA establishes preoperative diagnosis essential for planning of treatment. A 58-year-old woman is presented in whom CT demonstrated a space-occupying lesion of the orbit, diagnosed cytologically as metastatic breast cancer. Based on this cytological diagnosis, hormonal treatment was administered and unnecessary surgical intervention was avoided. PMID- 2258110 TI - [Late health sequelae of accidental bromine exposure]. AB - Health and environmental assessment of the consequences of accidental contamination of an area in the Negev desert is described and the effects of exposure to bromine vapor in 6 persons evaluated. They were only mildly affected during the acute spillage of the bromine, with some respiratory symptoms and first and second degree skin burns of small exposed areas on the legs. All were treated in hospital and were released within 1-4 days. 6-8 weeks later they demonstrated a complex array of complaints, including cough, shortness of breath, chest tightness, eye irritation, headache, dizziness, fatigue, memory disturbances, sleep and sexual disturbances. These complaints could not be substantiated by objective clinical or laboratory examination. There was thus obvious magnification of the complaints 1-2 months after the accident. PMID- 2258112 TI - [Prevalence of type 2 diabetes in the Negev]. AB - 10,578 medical records of patients 30 years and older, registered in 3 representative primary care clinics, were reviewed in 1984. 705 diabetics were identified. The prevalence rate was 6.7%: 5.9% among men and 7.1% among women. The male/female ratio was 46/54. In both sexes rates increased with age. The highest age-adjusted rate was among Jews of North African origin (7.5%). PMID- 2258113 TI - [Perforation of the small bowel, bleeding and ARDS as complications of typhoid]. AB - Ileal complications, including perforation and bleeding, are uncommon in the western world today. We report a 26-year-old man with typhoid fever who developed hypoxemia, pleural effusion, ileal perforation and ileal bleeding. He was treated with intravenous chloramphenicol and underwent 2 operations. The ileal complications developed during the third week of illness. To our knowledge this is the first such report in the Hebrew literature. PMID- 2258114 TI - [Epsilon aminocaproic acid for management of traumatic hyphema with large blood clot in the anterior chamber]. AB - Epsilon aminocaproic acid (EACA) is an antifibrinolytic agent currently used in the management of traumatic hyphema. It is effective in reducing the rebleed rate, but a long-standing blood clot in the anterior chamber predisposes to complications, such as corneal blood staining and elevated intraocular pressure. We assume that a large blood clot in the anterior chamber might be a contraindication to the use of EACA. PMID- 2258115 TI - [Genetic diagnosis in preimplantation embryos]. PMID- 2258116 TI - [Tumor necrosis factor and septic adult respiratory distress syndrome]. PMID- 2258117 TI - [Antibiotic prophylaxis for the prevention of infective endocarditis]. PMID- 2258118 TI - [How to detect causal risk factors?]. PMID- 2258119 TI - [Captopril--new additional applications]. PMID- 2258120 TI - [Cough of 20 years duration after drinking]. PMID- 2258121 TI - [Can medical research be carried out without animals?]. PMID- 2258122 TI - [Preparation and application of hippocampal slices to pharmacological studies]. PMID- 2258123 TI - [Effect of neurotropin on experimental osteoarthritis]. AB - The effect of Neurotropin on osteoarthritis was investigated in comparison with those of prednisolone and indomethacin. 1) There were remarkable decreases in the staining intensity to safranin-O and in the contents of uronic acid, total hexosamine and hexose in the articular cartilage of rabbits in which experimental osteoarthritis was induced by the injection of papain into the knee joint. In the Neurotropin-treated group, the decrease in the staining intensity to safranin-O and the contents of uronic acid, total hexosamine and hexose were evidently recovered. On the other hand, in the prednisolone- or indomethacin-treated group, the degeneration of the cartilage was even more pronounced than in the control group treated with papain alone. 2) Neurotropin had no effect on the autolytic degradation of cartilage, but promoted the incorporation of 14C-acetate into the proteoglycan in the articular cartilage of rabbits. 3) Both prednisolone and indomethacin inhibited the autolytic degradation and the incorporation of 14C acetate into the proteoglycan. These results suggested that the therapeutic effect of Neurotropin on osteoarthritis may be due to the improvement of decreased proteoglycan content in the matrix of articular cartilage; and in this respect, it is different from anti-inflammatory drugs such as prednisolone and indomethacin. PMID- 2258124 TI - [Ulcerogenic effect of a GABA derivative, baclofen, in the rat: effect of hypothermia]. AB - The ulcerogenic action of baclofen, a lipophilic derivative of GABA, was studied in the urethane anesthetized rat in relation to body temperature. Baclofen at the doses of 2, 4 and 8 mg/kg, s.c. induced gastric ulceration in a dose-dependent manner in the hypothermic (body temperature: 28-30 degrees C) rat. Duodenal ulcers were also observed in about 80% of the hypothermic animals treated with the highest dose of baclofen. Baclofen, even at 8 mg/kg, s.c., however, failed to induce gastric ulceration in the normothermic (body temperature: 37-38 degrees C) rat. Histamine, at the secretagogue dose causing acid secretion as potently as 8 mg/kg of baclofen, induced gastric ulcers in both the hypothermic and the normothermic rats. These results indicate that the ulcerogenic effect of baclofen is closely related to the thermoregulation mechanism and may provide important clues for clarifying the pathophysiology of gastroduodenal ulcers induced by hypothermic treatments such as water-immersion stress ulcers or cold exposure ulcers. PMID- 2258125 TI - [Sex differences and regulatory mechanism of epidermal growth factor receptor in the rat liver]. AB - The number of epidermal growth factor (EGF) receptor in rat hepatic membranes was about 2-hold higher in adult male than in adult female rats. Castration of adult males slightly decreased the EGF receptor number. Castration of neonatal males decreased the number of EGF receptors when they reached sexual maturity. This decrease was restored by the combination of neonatal and pubertal treatments with testosterone. Hypophysectomy caused a marked decrease in the number of EGF receptors in the male animals, and this decrease was not restored by either testosterone or triiodothyronine administration. Continuous administration of human growth hormone (hGH) with an osmotic minipump to normal males reduced the EGF receptor number. In contrast, intermittent administration of hGH twice a day (every 12 hr) to hypophysectomized males and/or normal females significantly increased the EGF receptor number. These results indicate that the number of EGF receptors in rat hepatic membranes is regulated by the secretory rhythm of GH in the pituitary, which may be "imprinted" by neonatal androgen. PMID- 2258126 TI - [General pharmacological properties of an anti-ulcer drug, azuletil sodium (KT1 32)]. AB - Azuletil sodium (AZE, 100 mg/kg, p.o.) did not affect the general behaviors, spontaneous motor activity, pentobarbital-induced hypnosis and body temperature. Furthermore, it did not elicit anticonvulsant and muscle relaxant actions. However, AZE (300 mg/kg, p.o.) elicited a stiff gate and slightly inhibited the spontaneous motor activity and electroshock-induced convulsions. It had no influence on spontaneous EEG activities, even at 30 mg/kg, i.v. AZE inhibited acetic acid-induced writhing moderately at doses above 100 mg/kg. AZE at concentrations up to 10(-5) g/ml did not affect agonist-induced contractions of the isolated ileum, trachea, vas deference and uterus, but inhibited serotonin and oxytocin-induced contraction at concentrations above 3 x 10(-4) and 10(-5) g/ml, respectively; and it also depressed spontaneous movements of the ileum and uterus at concentrations above 3 x 10(-4) g/ml. AZE caused no changes in blood pressure (BP), heart rate (HR), left ventricular pressure, ECG, tracheal pressure (TP), femoral blood flow (FBF) and coronary blood flow (CBF) at doses up to 10 mg/kg, i.v. in anesthetized dogs, but it caused an increase or a decrease in BP, an increase in TP and an increase in CBF at 30 mg/kg, i.v. However, even at 300 mg/kg, p.o., it caused no changes in BP and HR in conscious rats. AZE moderately promoted the charcoal transport. AZE at doses up to 300 mg/kg, p.o. did not affect urine volume, urinary electrolyte excretion, blood glucose and prothrombin time. These results suggest that AZE at anti-ulcer doses of 10-100 mg/kg, p.o. does not have noticeable effects on general pharmacological properties, and there is no marked differences as compared with those of GAS. PMID- 2258127 TI - [Soft tissue rheumatism. Frequent disease picture in the framework of non systemic inflammatory soft tissue rheumatism]. AB - The term nonarticular rheumatism covers a hetereogeneous group of diseases affecting the fatty tissue, periarticular tissue and muscles that often also appears, combined, in the form of peri-arthropathies. Without a doubt, the greatest importance attaches to the tendomyoses, which are characterized by spontaneous pain, in particular tenderness to touch, that appears at classical localisations. The most common causes are misalignment, microtrauma, overstraining, and occasionally internistic diseases. In many cases, the genesis is multifactorial, psychological factors also being involved. With respect to therapy, once noxae have been excluded, a range of predominantly physical and drug treatments are available, depending upon the acute nature of the disorder. PMID- 2258128 TI - [Hardening against the common cold--is it possible?]. AB - The common cold has great socio-economic impact. To date, no prophylaxis has been scientifically shown to be effective. A number of older reports implied that visits to the sauna and other thermotherapeutic measures might provide a certain degree of protection. More recent data suggest that this supposition is probably true. Nevertheless, there are a number of important questions still to be answered in this area. PMID- 2258129 TI - [Surgical therapy of spasmodic torticollis. Selective peripheral denervation]. AB - The authors report on their experience with 19 patients treated with a new operative procedure for spasmodic torticollis--microneurosurgical selective denervation of the hyperactive muscles. In comparison with earlier surgical approaches, the procedure, described by the Canadian neurosurgeon Claude Bertrand, is associated with a high success rate and an absence of the sequelae not infrequently seen with other procedures (stereotactic thalamotomy, intradural divisioning of the anterior roots C1-C3, etc.). The procedure is thus indicated whenever spasmodic torticollis still persists two years after onset, despite conservative therapy. PMID- 2258130 TI - [Infection of vascular prosthesis]. AB - Infections of vascular grafts are rare, but often life-threatening. Clinical signs and symptoms must be actively sought for, since the association with past vascular surgery is not always evident. Clinical history reveals fever, delayed wound healing, ischemia, or possibly gastrointestinal bleeding. Signs are wound infection, fever, septic emboli, or a new vascular murmur. Laboratory findings are non-specific. In most cases, diagnosis can be made by scintigraphy techniques. Treatment with antibiotics alone is seldom successful, and may be complicated by progressive infection (suture insufficiency). Mortality and morbidity of vascular graft infection are high, so that prophylaxis and early diagnosis are of paramount importance. PMID- 2258132 TI - [Utilization of zidovudine in the early stage of HIV infection. Lower dosages lessen toxicity]. PMID- 2258131 TI - [Gaviscon in reflux symptoms. Results of a drug monitoring study]. AB - 335 general practitioners participated in an observational study of the alginic acid-containing antacid preparation Gaviscon over a period of eight months. In this period, 2927 patients with reflux disease were treated. Some 62.3% of the patients were treated for six to eight days. Both the tablet and suspension forms of the drug were considered to be effective by both physician and patient in more than 94% of the cases. Drug toleration was also considered good in more than 95% of the cases. The taste of Gaviscon was described as good by 54.7% of the patients, and acceptable by 33.5%. Pregnant women with reflux symptoms were observed in a separate group (n = 52). PMID- 2258133 TI - Mechanism of insulin resistance in the post receptor events in sheep: 3-O methylglucose transport in ovine adipocytes. AB - A severe resistance to the stimulatory action of insulin on glucose metabolism has been shown in ruminant adipose tissue or isolated adipocytes as compared to that of rats. To elucidate the mechanism of insulin resistance in ruminants, we measured the stimulatory effect of insulin on 3-O-methylgulose transport and on intracellular glucose metabolism in isolated adipocytes from sheep and rats. At a glucose concentration (0.1 mM) where transport is thought to be rate-limiting for metabolism, lipogenesis from [U-14C]glucose by ovine adipocytes was markedly less than by rat adipocytes in both the basal state and at all insulin concentrations. The responsiveness to insulin assessed by percent increase above basal was reduced to about 15% of that in rat adipocytes, but the insulin sensitivity was similar, because the insulin concentration giving half-maximal stimulation, ED50, did not differ significantly between ovine and rat adipocytes. The maximal insulin-stimulated 3-O-methylglucose transport in ovine adipocytes per cell was less than 20% of that in rat adipocytes, with a significant lowering in basal rates of transport. However, when data was expressed per 3-O-methylglucose equilibrium space no significant differences were found between ovine and rat in the basal transport rates, but a lowered ability of insulin to stimulate glucose transport was still seen in ovine adipocytes. The dose-response curve for glucose transport was slightly shifted to the right in ovine adipocytes compared to rat adipocytes, indicating a small decrease in insulin sensitivity. The decrease in glucose transport was due to 60% reduction in the maximum velocity in the insulin -stimulated state, with no change in the Km. PMID- 2258134 TI - Obtaining a representative blood sample in lactate tracer studies. AB - Reasons why venous tracer infusion with arterial sampling [(v-a) mode] has advantages compared to arterial infusion and venous sampling [(a-v) mode] for studies of blood lactate kinetics are presented. Arterial tracer infusion can result in biased tracer input due to streaming and unequal blood flow distribution. The procedure is impractical for human studies. Venous sampling from the jugular, or any other peripheral or great vein, provides a sample which may, or may not represent mixed venous systemic blood, which exists only in the pulmonary artery. Venous sampling will not represent cardiac lactate metabolism because the coronary arteries drain into the coronary sinus. Venous sampling, as well as pulmonary artery sampling, will also ignore lactate metabolism in the lungs which drain into the left atrium from bronchial and pulmonary circulations. Turnover rates calculated from either venous or arterial specific activities underestimate true tissue turnover. Correction for either measurement depends on good estimates of blood flows to lactate exchanging and non-exchanging tissue. Equilibration between lactate and pyruvate pools does not invalidate the use of tracers to measure lactate turnover. The (v-a) mode with venous infusion and arterial sampling has advantages for lactate tracer studies. PMID- 2258135 TI - Increased lactate appearance and reduced clearance during hypoxia in dogs. AB - In order to assess the effects of severe hypoxia on whole body glucose and lactate kinetics, nine experiments were performed on anesthetized, ventilated mongrel dogs. [U-13C]glucose and [1-14C]lactate (n = 5), or [6-14C]glucose and [U 13C]lactate (n = 4) were infused using the primed-continuous infusion method. Cardiac output was measured by thermodilution. After a control period with 21% O2, inspired O2 was reduced for 90 minutes. Three of the experiments resulted in unstable hemodynamics and lactate levels, and are excluded from the mean data. Arterial PO2 fell from a control level of 106.8 +/- 11.9 to 24.2 +/- 3.5 mmHg during the last 45 minutes of hypoxia, and O2 transport fell to 52% of normoxic values. Arterial lactate concentration and the rate of appearance increased by 428% and 182%, respectively, from control to hypoxia. The metabolic clearance rate for lactate fell by 34%. Arterial glucose levels did not change significantly with hypoxia, but the rate of glucose disappearance rose by 70%, and the rate of glucose conversion to lactate increased 3-fold. It is concluded that acute severe hypoxia in anesthetized dogs causes 1) a large increase in arterial lactate levels, but no significant change in glycemia, 2) a large increase in the rate of lactate disappearance and only a small increase in the rate of glucose disappearance and 3) a fall in the metabolic clearance rate of lactate. PMID- 2258136 TI - Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4". AB - Recent studies of cellular T4 and T3 uptake have indicated active transport of the hormones into the cell rather than passive diffusion of the non-protein bound fraction. In order to study the significance of the extracellular environment, oxygen consumption and glucose uptake were examined in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen-consumption in a dose dependent manner but the T4 stimulation was dependent on the total concentration of T4 and did not differ between serum incubation or non-protein containing medium. Addition of ANS (100 mg/l) which inhibits binding of T4 to TBG, did not increase T4 effect in serum. Inhibition of the NaK-ATPase by addition of ouabain (9-72 mg/l) did not inhibit T4 stimulation, thus indicating that the ouabain sensitive NaK-ATPase is not a major component of the processes which initiate the intracellular effects of T4. Therefore the stimulation of uptake of oxygen and glucose in human mononuclear blood cells seems to be dependent on the total concentration of T4 and not on the non-protein bound (free) fraction suggesting active membrane uptake of T4, as the limiting factor for intra-cellular hormone effect. PMID- 2258137 TI - Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid Graves' disease. AB - Lipid metabolism was examined in patients with hyper- or hypothyroidism. Compared with corresponding age and sex matched controls, serum total cholesterol (T chol), low density lipoprotein cholesterol (LDL-chol), phospholipid (PL) and LDL levels were significantly low and free fatty acid (FFA) levels were high with apparently normal triglyceride (TG), very low density lipoprotein (VLDL) and high density lipoprotein cholesterol (HDL-chol) levels in 61 hyperthyroid patients, while T-chol, LDL-chol, TG, PL, VLDL and LDL levels were high with normal FFA and HDL-chol levels in 31 hypothyroid patients. Serum lipid levels were then repeatedly measured in 7 men and 7 women with hyperthyroid Graves' disease before treatment (stage I), just after the patients became euthyroid with anti-thyroid drug (stage II) and more than 2 months after the patients remained euthyroid (stage III). Serum T-chol, LDL-chol, PL and LDL levels were low at stage I, significantly elevated at stage II and then normalized at stage III. Transient but significant elevation of serum TG, VLDL and HDL-chol levels at stage II were also observed in men. Accelerated catabolism and anabolism of lipid has been reported in hyperthyroidism. Transient elevation of serum lipid levels suggests a more rapid improvement in catabolism than in anabolism of lipid in an early stage of the medical treatment for hyperthyroidism. PMID- 2258138 TI - No change of beta-endorphin plasma levels during hyperglycemic glucose clamping in obese patients and lean controls. PMID- 2258139 TI - Muscle uptake of inorganic phosphorus during oral glucose challenge. PMID- 2258140 TI - Csf arginine-vasopressin decreases during dehydration in a patient with post traumatic diabetes insipidus. PMID- 2258141 TI - Repetitive injections of GHRH in normal children and adults. PMID- 2258142 TI - Interferon antibodies may negate the antiviral effects of recombinant alpha interferon treatment in patients with chronic hepatitis B virus infection. AB - In a randomized controlled trial of recombinant alpha-2a interferon for chronic hepatitis B, interferon antibodies developed in 21 (39%) of 54 Chinese adults who received IFN. No correlation was observed between sex, age, pretreatment serum ALT level or liver histological findings and the development of interferon antibodies. Antibodies were significantly more likely to develop in patients who received lower doses (2.5 or 5 MU/m2) of alpha-2a interferon than in those who received a higher dose (10 MU/m2): 53% vs. 11% (p = 0.006). The development of interferon antibodies appeared to reverse the initial antiviral response to treatment, with reappearance of hepatitis B virus DNA in serum in 12 patients and HBeAg in three patients. Sustained clearance of HBeAg was achieved in only one (5%) patient but was achieved in seven (21%) patients without interferon antibodies. The mere presence of interferon antibodies did not preclude an antiviral response to interferon therapy, but patients with high titer neutralizing antibodies were less likely to respond. These findings suggest that interferon antibodies may negate the antiviral effects of alpha-2a interferon. A higher incidence of interferon antibodies in Chinese vs. white patients with chronic hepatitis B may contribute to the poorer antiviral response in Chinese patients. PMID- 2258143 TI - A biphasic pattern of anti-pre-S responses in acute hepatitis B virus infection. AB - The clinical relevance of the immune response to the translation products of the pre-S1 and pre-S2 regions of hepatitis B virus was examined by testing sequential serum samples from 17 patients with acute self-limited hepatitis B and from two patients in whom chronic liver disease developed. Anti-pre-S antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre-S1 and pre-S2 sequence. In acute, self-limited infection, anti-pre-S antibodies appeared in a biphasic pattern. The early antibodies were detected at the time of clinical signs of acute disease when HBsAg and often HBeAg were present, but hepatitis B virus DNA was no longer detectable in serum. Anti-pre-S levels then fell, but subsequently reappeared as the late antibody during the recovery phase, after development of anti-HBe, but before anti-HBs. Anti-pre-S responses were detected in 15 of 17 patients who recovered (88.2%) and in both patients with acute hepatitis B virus infection evolving to chronic liver disease. Although the early antibodies to pre-S1 and pre-S2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self-limited infection, these antibodies also were transiently or continuously present with high levels of serum hepatitis B virus DNA in patients in whom chronic hepatitis B infection developed. Thus the anti-pre-S response in acute hepatitis is not a prognostic marker for clinical resolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258144 TI - Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection. AB - To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays. Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p less than 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p less than 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%). The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258145 TI - Defects in the precore region of the HBV genome in patients with chronic hepatitis B after sustained seroconversion from HBeAg to anti-HBe induced spontaneously or with interferon therapy. AB - Hepatitis B virus DNA clones were propagated from sera of six patients with chronic hepatitis B who seroconverted from HBeAg to antibody to HBeAg either spontaneously or after administration of alpha-interferon. Defects in the precore region blocking synthesis and secretion of HBeAg were detected in all 46 hepatitis B virus DNA clones from three patients who remained positive for antibody to HBeAg and in whom hepatitis resolved. Defective clones had point mutations from guanine to adenine at nucleotide 83 in the precore region, converting codon 28 from tryptophan (TGG) to a stop codon (TAG). In contrast, this defect was not found in any of 39 hepatitis B virus DNA clones from three patients who seroconverted to antibody to HBeAg but then redeveloped HBeAg with reactivation of hepatitis. Using these results, the G-to-A point mutation at nucleotide 83 in the precore region would predict sustained positivity for antibody to HBeAg and remission of hepatitis in patients who have seroconverted either spontaneously or with interferon therapy. PMID- 2258146 TI - Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells. AB - The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258147 TI - The human hepatic asialoglycoprotein receptor is a target antigen for liver infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis. AB - Autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50% of the sera of patients with autoimmune chronic active hepatitis and in 15% of patients with primary biliary cirrhosis. In this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for T cell-mediated immune responses. Peripheral blood lymphocytes of 37% (7 of 19) of patients with autoimmune chronic active hepatitis and 33% (2 of 6) of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor, whereas no proliferation was found with peripheral blood lymphocytes of patients with chronic viral hepatitis (0 of 13) and healthy blood donors (0 of 4). Moreover, we isolated T-cell clones from liver biopsy samples of two patients with autoimmune chronic active hepatitis and two patients with peripheral blood lymphocytes. Between 2.8% and 14.3% of these clones showed a specific proliferative response to purified human hepatic asialoglycoprotein receptor. The response was restricted to autologous antigen-presenting cells and could be blocked by monoclonal antibodies against human leukocyte antigen-DR molecules. The response of T cells to the human hepatic asialoglycoprotein receptor did not require the lectinlike activity of the asialoglycoprotein receptor. Thus the human hepatic asialoglycoprotein receptor could be identified as a major target antigen of humoral and cellular immune reactions in autoimmune-mediated liver diseases. PMID- 2258148 TI - Primary culture of adult rat hepatocytes after 48-hour preservation of the liver with cold UW solution. AB - Rat livers were perfused and stored for 48 hr in cold University of Wisconsin solution before dissociation by the two-step collagenase method. At that time, glycogen content was significantly reduced, but no obvious changes in albumin, beta-actin and aldolase B mRNAs and in glutathione levels were observed. Enzymatic perfusion yielded 280 +/- 30 x 10(6) viable hepatocytes vs. 520 +/- 40 x 10(6) viable hepatocytes from unstored organs. Cell viability determined by trypan blue exclusion was 74% and 90%, respectively. Hepatocytes from University of Wisconsin-preserved livers had a 29% reduced adenosine triphosphate content, but glutathione levels did not significantly differ from those found in unstored cells. When put into culture, hepatocytes formed typical monolayers of granular epithelial cells and did not exhibit alteration of their fine structure when compared with cells from unstored organs. After 24 and 48 hr, they showed variations in cytochrome P-450 content and ethoxyresorufin O-deethylase activity similar to those observed with unstored cells. By contrast, overall protein synthesis and albumin secretion rate were 40% and 30% lower, respectively. Hepatocytes from University of Wisconsin-preserved organs could be cryopreserved and further cultured as unstored cells. The University of Wisconsin solution was also used to preserve isolated hepatocytes. Viability of freshly isolated hepatocytes was decreased by only 10% after 48 hr of hypothermic liver storage when assayed by intracellular lactate dehydrogenase content. However, after 4 hr of storage, in contrast with hepatocytes preserved in L15 Leibovitz medium, the cells attached poorly to plastic and exhibited morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258149 TI - Decreased toxicity of polymorphonuclear neutrophils toward hepatocytes isolated from rats with acute inflammatory reaction. AB - We have recently demonstrated that polymorphonuclear neutrophils were toxic to hepatocytes through a protease-mediated mechanism. Since synthesis of antiproteases is markedly increased during acute inflammatory reaction, the aim of this work was to investigate the toxicity of neutrophils against normal vs. inflammatory rat hepatocytes. Acute inflammatory reaction was induced by subcutaneous injection of turpentine 24 hr before the experiments. Hepatocytes from normal and turpentine-treated rats were isolated by collagenase digestion. They were incubated with human neutrophils stimulated by 1 mg/ml opsonized zymosan. Cytotoxicity was quantified by the percentage of alanine aminotransferase activity released by hepatocytes in culture medium after an 18 hr incubation period. By comparison to normal hepatocytes, inflammatory hepatocytes were more resistant to the toxicity of neutrophils. At a neutrophil/hepatocyte ratio of 20:1, the alanine aminotransferase activity releases were 53.7% +/- 5.4% (mean +/- 1 S.E.) and 27.4% +/- 4.8% for normal and inflammatory hepatocytes, respectively. Similarly, inflammatory hepatocytes were found to be less sensitive than normal hepatocytes to the toxic effect of purified neutrophil cathepsin G. In contrast, both types of hepatocytes exhibited the same sensitivity to H2O2 generated by a system consisting of glucose and glucose oxidase. Two arguments suggested that the resistance of inflammatory hepatocytes to protease toxicity was explained by an increased production of antiproteases by these cells: (a) when tested against cathepsin G and porcine pancreatic elastase activities, the protease inhibitory capacity of conditioned medium from inflammatory hepatocytes was higher than that of conditioned medium from normal hepatocytes; (b) conditioned medium from inflammatory hepatocytes markedly reduced the toxicity of stimulated neutrophils as that of cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258150 TI - Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. AB - Microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression. We have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short-term metabolic support to improve the survival of animals with galactosamine-induced fulminant hepatic failure. Here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long-term metabolic liver support in Gunn rats. Gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia. We studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function. Free hepatocytes, isolated from male Wistar rats, were microencapsulated with collagen within a trilayered sodium alginate-poly-L-lysine sodium alginate membrane using techniques developed in our laboratory. A total of 45 Gunn rats underwent intraperitoneal transplantation with free hepatocytes (5 x 10(7], isolated encapsulated hepatocytes (5 x 10(7], control (empty) microcapsules or no transplant (untreated controls). Serum bilirubin levels were monitored daily for 10 days after transplantation, and subsequent weekly samples were obtained for up to 1 mo. Microcapsules were studied by light and electron microscopy 1 mo after transplantation. During the first week after transplantation, the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes, free hepatocytes and control microcapsule transplanted groups was 45.7%, 18.6% and 14.3%, respectively. For up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34.8%, 13.5% and 3.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258151 TI - Normalization of ventilation/perfusion relationships after liver transplantation in patients with decompensated cirrhosis: evidence for a hepatopulmonary syndrome. AB - To examine the effect of liver transplantation on the respiratory and cardiovascular functions, ventilation/perfusion relationships were determined by multiple inert gas elimination technique in six patients with end-stage liver disease 1 to 19 mo before and 2 to 6 mo after liver transplantation. Cardiac output and pulmonary vascular pressures were measured after catheterization of the pulmonary artery. All patients had normal spirometry and chest x-ray films before transplantation. PaO2 before transplantation was 78.8 +/- 7.4 mm Hg (range = 51.8 to 102.8 mm Hg). All patients had perfusion of poorly ventilated lung regions (low ventilation/perfusion relationships) varying from 3% to 19% of cardiac output (mean = 8.5% +/- 2.4% of cardiac output) and two patients had intrapulmonary shunting (3% and 20% of cardiac output). Measured and calculated PaO2 agreed closely, indicating absence of pulmonary diffusion abnormality, as well as of extrapulmonary shunting. After transplantation, PaO2 normalized in all patients, and both shunting and low ventilation/perfusion relationships disappeared. Cardiac output decreased from 9.1 +/- 1.4 to 6.6 +/- 0.5 L/min (p less than 0.05), and the pulmonary vascular resistance increased from 0.69 +/- 0.14 to 1.64 +/- 0.43 mm Hg/L/min (p less than 0.05). The systemic vascular resistance also increased (before = 8.7 +/- 1.0; after = 15.3 +/- 1.1 mm Hg/L/min; p less than 0.001). Normalization of respiratory and cardiovascular alterations, after liver transplantation, in patients with end-stage liver disease indicates that these changes have a direct functional relationship to the diseased liver. It is hypothesized that this is part of a "hepatopulmonary syndrome,' which in similarity to the hepatorenal syndrome disappears with improved liver function. PMID- 2258152 TI - Electron microscopic observations on the accumulation of large granular lymphocytes (pit cells) and Kupffer cells in the liver of rats treated with continuous infusion of interleukin-2. AB - Treatment schedules were investigated for in vivo induction of lymphokine activated killer cells in the rat liver. Treatment of rats with continuous systemic or regional infusion of recombinant human interleukin-2 with a dose of 4 to 8 x 10(4) U/day during 7 days, resulted in an increase in number of large granular lymphocytes or pit cells in the liver up to 43 times normal. Kupffer cells, nongranular lymphocytes, monocytes and neutrophils also increased in number, but with a maximal fivefold increase this was much less pronounced than for large granular lymphocytes. Kupffer cells showed morphological signs of activation and were frequently seen in mitosis. Frequent mitoses were also observed for large granular lymphocytes, but not for other leukocytes. This indicates that the effect of interleukin-2 treatment on hepatic (sinusoidal) cells was primarily directed to large granular lymphocytes and Kupffer cells. The large granular lymphocyte accumulation occurred mainly intrasinusoidally, but they were also frequently observed in the space of Disse where they are not found in control rats. This may be explained partly by the observed damage or gaps in the endothelial lining. The intrasinusoidal large granular lymphocytes adhered to the endothelium and to Kupffer cells. Higher responses, for all cell types, were found when interleukin-2 was administered regionally, that is, through the hepatic artery rather than through the systemic route (jugular vein), although the differences were not statistically significant. Doses below 4 x 10(4) U/day did not result in significant increases of large granular lymphocytes in the liver. PMID- 2258153 TI - Differential regulation of liver P-450III cytochromes in choline-deficient rats: implications for the erythromycin breath test as a parameter of liver function. AB - Progressive liver fibrosis in rats develops when they are fed a diet deficient in choline. This diet also results in a pronounced and selective decrease in the liver microsomal content of a phase I drug-metabolizing enzyme belonging to the cytochrome P-450III gene family. Because P-450III cytochromes characteristically catalyze the N-demethylation of erythromycin, we believed that the production of breath CO2 from erythromycin would be dramatically reduced in choline-deficient rats. However, when 12 choline-deficient rats were compared with 9 control rats, the reduction in CO2 production from erythromycin (mean decrease 71%) was essentially identical to that from aminopyrine (mean decrease 69%), a substrate believed to be metabolized normally by the hepatocyte in fibrotic liver disease. Furthermore, we found that the relative erythromycin and aminopyrine demethylase activities were comparable when measured in vitro in liver microsomes prepared from the choline-deficient rats. To determine the molecular basis for the erythromycin demethylase activity in the choline-deficient rats, the liver microsomes were subjected to immunoblot analysis using a variety of polyclonal and monoclonal antibodies capable of distinguishing individual P-450III-related proteins. Our studies confirm that a major erythromycin demethylase belonging to the P-450III family, termed P-450p, was greatly reduced in the choline-deficient rat liver. However, the specific concentration of a second P-450p-related protein was essentially normal and that of a third P-450p-related protein was actually increased in the choline-deficient rat liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258154 TI - Rapid decrease of cytochrome P-450IIE1 in primary hepatocyte culture and its maintenance by added 4-methylpyrazole. AB - Studies were conducted to evaluate the possible induction or the maintenance of cytochrome P-450IIE1 in primary hepatocyte cultures by the inducing agent 4 methylpyrazole. Hepatocytes were isolated from control (noninduced) rats and from rats treated in vivo with either pyrazole or 4-methylpyrazole to induce P 450IIE1. The content of P-450IIE1 was determined by Western blots with antipyrazole P-450 IgG, and catalytic activity was assessed by assays of dimethylnitrosamine demethylase activity. The treatment with 4-methylpyrazole in vivo increased the content of P-450IIE1 and dimethylnitrosamine demethylase activity sevenfold and fourfold, respectively. In cultures prepared from noninduced hepatocytes, P-450IIE1 levels fell to values of 76%, 65%, 31% and 1% of freshly isolated hepatocytes after 1, 3, 6 and 9 days in culture. A similar decrease in dimethylnitrosamine demethylase was observed during this time. In cultures prepared from induced hepatocytes, the decline in P-450IIE1 was more rapid as levels fell to 77%, 31%, 3% and 3% of initial values after 1, 3, 6 and 9 days in culture. Again, the fall in dimethylnitrosamine demethylase activity paralleled the decline in content of P-450IIE1 and was more rapid with the induced hepatocytes. With cultures prepared from noninduced or induced hepatocytes, the addition of 4-methylpyrazole in vitro did not increase the content of P-450IIE1 or the activity of dimethylnitrosamine demethylase over the initial values. However, 4-methylpyrazole appeared to stabilize the P-450IIE1 and to decrease its rate of decline in culture. In noninduced cultures, the percent remaining content of P-450IIE1 after 6 days was 31% in the absence of and 52% in the presence of 5 mol/L 4-methylpyrazole. In cultures from 4-methylpyrazole induced hepatocytes, the percent remaining P-450IIE1 after 3 days was 31% in the absence of inducer and 59% with 4-methylpyrazole added in vitro. Similarly 4 methylpyrazole helped to prevent the rapid decline of dimethylnitrosamine demethylase activity in induced and noninduced cultures. Viability of the induced and noninduced cultures in the absence or presence of added 4-methylpyrazole was similar. Levels of mRNA for P-450IIE1 were similar for livers from control rats and from rats treated in vivo with 4-methylpyrazole. The mRNA levels rapidly declined in induced and noninduced cultures, and this decline, unlike the fall in P-450IIE1 or dimethylnitrosamine demethylase activity, could not be prevented by the addition of 4-methylpyrazole in vitro to the cultures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258155 TI - Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. AB - Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect. PMID- 2258156 TI - Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload. AB - After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of the study, the size of the inclusions (which were not membrane-limited) increased to greater than 3 microns in diameter, occupying greater than 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes. PMID- 2258158 TI - Hepatology: what a difference a decade makes. PMID- 2258159 TI - Quantification of hepatic iron with CT and MRI: practical considerations. PMID- 2258157 TI - Preventive therapy of first gastrointestinal bleeding in patients with cirrhosis: results of a controlled trial comparing propranolol, endoscopic sclerotherapy and placebo. AB - Propranolol and endoscopic sclerosis of esophageal varices are the two approaches currently used in prophylaxis of the first gastrointestinal hemorrhage in the cirrhotic patient. One hundred twenty-six cirrhotic patients with esophageal varices and no histories of bleeding were included in the trial regardless of the gravity of the cirrhosis or the size of the esophageal varices. Patients with hepatocarcinomas or other cancers, clearly impossible follow-up, previous treatment for portal hypertension or contraindication to beta-blockers were excluded. After randomization, 43 patients received propranolol twice daily at a dose reducing the heart rate by 25%; 42 patients were treated with intravariceal and extravariceal injections of Polidocanol; 41 control patients received vitamin K orally as placebo. The patients were seen at 3-mo intervals for 2 yr. On entry to the trial the three groups were comparable in terms of clinical and biological parameters, including size of esophageal varices (grade I = 51, grade II = 54, grade III = 17), Child-Pugh classification (A = 29, B = 61, C = 32) and the origin of cirrhosis (alcoholic in 79% of cases). Twenty-four patients bled (two bled in the propranolol group, nine bled in the endoscopic sclerosis of esophageal varices group and 13 bled in the placebo group). Actuarial estimates (Kaplan-Meier) of the time of onset of first bleeding showed that the differences were significant between propranolol and placebo (p less than 0.004) and between propranolol and sclerotherapy (p less than 0.03) but not between sclerotherapy and placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258160 TI - Hepatocyte swelling stimulates macromolecular synthesis. PMID- 2258161 TI - Intrahepatic expression of HBcAg in chronic HBV hepatitis: lessons from molecular biology. PMID- 2258162 TI - Splanchnic vasodilation and renal vasoconstriction: a key to the hepatorenal syndrome? PMID- 2258163 TI - Mechanism for binding of fatty acids to hepatocyte plasma membranes: different interpretation. PMID- 2258164 TI - Hepatology Elsewhere: au revoir. PMID- 2258165 TI - Hepatocyte enlargement and portal hypertension. PMID- 2258166 TI - Even the French foie gras de canard does not induce portal hypertension. PMID- 2258167 TI - Branched-chain ketoacids in encephalopathy. PMID- 2258168 TI - Macrophages and interdigitating reticulum cells in normal human thymus and thymomas: immunoreactivity for interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha. AB - Pairs of monoclonal/polyclonal antibodies directed against interleukin-1 (IL-1) alpha, IL-1 beta and tumour necrosis factor (TNF) alpha were used for immunocytochemical identification of cytokine-containing cells in cryostat sections of human fetal thymuses and thymomas. In the fetal thymus immunoreactivity for IL-1 alpha was mainly confined to the medulla and was detected in S-100 positive interdigitating reticulum cells. The pattern of immunoreactivity for IL-1 beta was similar to that for IL-1 alpha, but the number of positive cells was much lower. Cells positive for TNF alpha were extremely rare in the fetal thymus. In 11 thymomas macrophages were constantly present and were regularly distributed throughout the tumour, whereas S-100 positive interdigitating reticulum cells were fewer and were characterized by a zonal distribution. Thymoma-associated macrophages were negative for IL-1 beta and were poorly reactive for IL-1 alpha, only a few positive cells being detected in five of the cases. Some macrophages with immunoreactivity for TNF alpha were detected in seven cases; they formed rosettes with surrounding lymphocytes or were located in a perivascular position. A marked immunoreactivity for TNF alpha was constantly detected in mast cell granules, which were observed in nine thymomas but not in fetal thymus. Positive immunoreactivity of interdigitating reticulum cells for IL-1 alpha was confirmed in five reactive lymph nodes and was also observed in Langerhans' cells in dermatopathic lymphadenitis. Our findings suggest that IL-1 alpha is a crucial molecule for interdigitating reticulum cell and Langerhans' cell function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258169 TI - Comparative phenotypes in rhabdomyosarcomas and developing skeletal muscle. AB - The morphological and immunohistochemical phenotypes of 51 rhabdomyosarcomas from young people have been described and contrasted with phenotypes in developing skeletal muscle from 20 fetuses and neonates. The tumours express markers in a cumulative and consistent sequence--vimentin, desmin, fast myosin, myoglobin- which evolves pari passu with morphological differentiation and follows the same pattern found in normal myogenesis. Changes in immunohistochemical phenotype are documented in residual and recurrent tumours excised after chemotherapy. The presumptive rhabdomyoblastic nature of some primitive tumours, marking with vimentin alone, is discussed. PMID- 2258170 TI - Oestrogen receptor in breast cancer: prognostic studies using a new immunohistochemical assay. AB - A recently developed and validated histochemical method--immunogold-streptavidin enhancement--was used to determine oestrogen receptor content in paraffin sections of breast cancers. The selection of the best cut-off point to define oestrogen receptor status as rich or poor was made on the basis of survival data, using the following indices: survival to term; disease-free interval; survival at 5 years; and disease-free interval at 5 years. Oestrogen receptor status was examined in relation to histological grade, lymph node status, menopausal status and tumour size and these four indices were considered as independent prognostic factors. Semi-quantitative assay of receptor content showed that increasing content was related to better prognosis. Adjuvant therapy alone had no effect on patient outcome. Independently, histological grade and lymph node status, but not menopausal status or tumour size, were prognostic indicators. Oestrogen receptor rich status, as measured by immunogold-streptavidin, in conjunction with certain of these factors indicated a better prognosis. This was comparable with results in reports using other methods of receptor assay. We found the oestrogen receptor status and menopausal status more significant at 5 years than at term. The advantage of immunogold-streptavidin enhancement, which we found as reliable as other methods for oestrogen receptor assay, is that it can be used on archival, routinely paraffin-processed material. PMID- 2258171 TI - Stereological estimates of nuclear volume in normal germ cells and carcinoma in situ of the human testis. AB - Carcinoma in situ of the testis may appear many years prior to the development of an invasive tumour. Using point-sampled intercepts, base-line data concerning unbiased stereological estimates of the volume-weighted mean nuclear volume (nuclear vV) were obtained in 50 retrospective serial testicular biopsies from 10 patients with carcinoma in situ. All but two patients eventually developed an invasive growth. Testicular biopsies from 10 normal adult individuals and five prepubertal boys were included as controls. Nuclear vV in testicular carcinoma in situ was significantly larger than that of morphologically normal spermatogonia (2P = 1.0 x 10(-19)), with only minor overlap. Normal spermatogonia from controls had, on average, smaller nuclear vV than morphologically normal spermatogonia in biopsies with ipsi- or contra-lateral carcinoma in situ (2P = 5.2 x 10(-3)). No difference in nuclear vV was found in carcinoma in situ with or without co existing invasion, and no characteristic pattern of nuclear vV was disclosed by following the lesion in serial biopsies over time from individual patients. Estimation of nuclear vV may represent an adjuvant tool in morphologically puzzling cases of testicular carcinoma in situ, but the prognostic value requires further evaluation in larger series of patients. PMID- 2258172 TI - Congenital testicular lymphangiectasis in children with otherwise normal testes. AB - Two cases of testicular lymphangiectasis are reported, occurring in stillborns. The disease is a congenital malformation consisting of an abnormal expansive development of lymphatic vessels in both testes. Autopsy study revealed the absence of pulmonary, intestinal or systemic lymphangiectasis. The testes showed normal tubular development with normal germ cell numbers and also normal Leydig cell numbers. The epididymis and spermatic cord appeared normal. In contrast with the two previously reported cases of testicular lymphangiectasis, the present cases were not associated with cryptorchidism or other malformations. PMID- 2258173 TI - Neonatal haemochromatosis. AB - Four cases of neonatal haemochromatosis presenting as fulminant hepatic failure in the newborn were diagnosed by autopsy. In all four cases the diagnosis was made by histochemical demonstration of excessive iron deposition in hepatocytes and extrahepatic parenchymal cells, particularly pancreatic acinar epithelium, thyroid follicular epithelium and distal renal tubules. No haemosiderin was detectable in the extrahepatic mononuclear-phagocytic cells of the spleen, lymph nodes and bone marrow. The liver was the most severely affected organ. The hepatic haemosiderosis was associated with massive hepatocellular necrosis of prenatal onset in three patients, one of whom showed formation of regenerative nodules, establishing true congenital cirrhosis. Other inconstant findings included giant cell transformation, diffuse sinusoidal fibrosis with segregation of small groups of hepatocytes and cholestasis with pseudoacinar change of liver cell plates. The fetal liver disease had its onset in the late second trimester of pregnancy and was reflected clinically by severe panhypoproteinaemia with non immune hydrops; hyperbilirubinaemia and haemorrhagic diatheses were apparent in the newborn. Neonatal haemochromatosis is a metabolic disorder, probably of autosomal recessive inheritance. The site and nature of the basic defect remain uncertain. Pathologists should be aware of this condition and its potential recurrence in subsequent pregnancies. PMID- 2258174 TI - Multicystic structures appearing in mature cystic teratomas of the ovary: an immunohistochemical and ultrastructural study. AB - Multicystic or sieve-like areas are frequently present in the walls of mature cystic ovarian teratomas. This histological, immunohistochemical and ultrastructural study supports the contention that such cysts arise from oleous material which has been extravasated through the cyst wall and become lodged within fibrous tissue and small blood vessels. Some cysts may also arise from degenerate sebaceous glands. PMID- 2258175 TI - Hurthle cell neoplasms of the thyroid gland: an immunohistochemical study. PMID- 2258176 TI - Benign mucinous metaplasia of the vulva. PMID- 2258177 TI - Granular cell variant of dermatofibrosarcoma protuberans. PMID- 2258178 TI - Neurilemmoma of kidney--a rare occurrence. PMID- 2258179 TI - The effects of a simulated head-up display speedometer on perceptual task performance. AB - This study compared the effects of simulated head-up display (HUD) and dashboard mounted digital speedometers on key perceptual driving tasks in a simulated driving environment. Subjects were 20 male and female volunteers ranging in age from 19 to 51 years. A videotape, taken from the driver's perspective, of a car traveling along a memorized route served as the test scene. While viewing the test scene subjects performed tasks related to navigation, speed monitoring, and salient cue detection. The simulated HUD speedometer produced generally superior performance on the experimental tasks; most important, it enabled subjects to respond significantly more quickly to the salient cues. Implications for the effects of HUDs on automobile safety are discussed. PMID- 2258180 TI - The relation of vergence effort to reports of visual fatigue following prolonged near work. AB - Two experiments examined the link between vergence effort and subjective reports of visual fatigue following prolonged near work. In Experiment 1, dark vergence and reports of visual fatigue symptoms associated with computer use were measured in 104 persons. Dark vergence was significantly correlated with four of six symptoms of visual fatigue. In Experiment 2, 16 subjects who exhibited clear "Heuer effects" (systematic gaze-related changes in dark vergence) read from a video display terminal (VDT) at a distance of 20 cm for 60 min under two gaze elevation conditions: 20 deg above and 20 deg below a baseline gaze elevation. This manipulation was designed to vary the amount of vergence effort required to fixate the VDT. Results indicate a positive relation between vergence effort and visual fatigue both within and between subjects, and that prolonged near work leads to decreased vergence accuracy at far distances. Implications for VDT workstation design are discussed. PMID- 2258181 TI - Static anthropometry of civilian Chinese in Taiwan using computer-analyzed photography. AB - The purpose of this study was to establish a static anthropometric data bank for Chinese civilians in Taiwan using a computer-analyzed photographic method. Stratified random sampling was applied to decide the sampling site; sample size was established by considering standard errors in a pilot study. Then a photographic method was employed in addition to direct measurement of selected body dimensions. In all, 933 subjects were measured. The data were entered via a digitizer into a microcomputer for processing. The resulting anthropometric data bank was organized by age, sex, and occupational groupings. Comparisons with data from previous studies were made, and recommendations for further research presented. PMID- 2258182 TI - Specific amplification of rearranged immunoglobulin variable region genes from mouse hybridoma cells. AB - In this article we show how the polymerase chain reaction (PCR) and primers designed for conserved sequences of leader (L), framework one (FR1) and constant (CONST) regions of immunoglobulin light and heavy chain genes can be used for the cloning and sequencing of rearranged antibody variable regions from mouse hybridoma cells. RNA was extracted from the mouse hybridoma cells secreting MAbs: IOR-T3a (anti-CD3), C6 (anti-P1 of N. meningitidis B385), IOR-T1 (anti-CD6), CB CEA.1 (anti-carcinoembryonic antigen), and CB-Fib.1 (anti-human fibrin). First strand cDNA was synthesized and amplified using PCR. The newly designed primers are superior to others reported recently in the literature. Isolated PCR DNA fragments of C6 and IOR-T3a were sequenced after asymmetric amplification, or M13 cloning. The FR1/CONST primer combinations selectively amplified mouse lights chain of groups kappa II, V, and VI, and heavy chains of groups IIa and IIc. The L/CONST primers for light chains amplified light chains from all four hybridomas. These methods greatly facilitate structural and functional studies of antibodies by reducing the efforts required to clone and sequence their variable regions. PMID- 2258183 TI - The in vivo and in vitro use of monoclonal antibody for the deletion of phagocytic cells in guinea pigs. AB - A monoclonal antibody (MAb) was raised against guinea pig macrophages and its reactivity to bone marrow derived cells was tested. The Ab selectively reacted to phagocytic cells such as polymorphonuclear leukocytes (PMNL) and macrophages, but not to erythrocytes, lymphocytes, hepatocytes and platelets, as determined by the binding and complement-dependent cytolytic activity. In vivo effect of the Ab on peripheral leukocytes was tested. More than 90% of PMNL were deleted 3 hours after the intravenous administration of the antibody. The cells started to reappear in peripheral blood on the 3rd day and returned to the level before the administration on the 6-7th day. Erythrocytes in peripheral blood were not affected. Phytohemagglutinin (PHA) and muramyl dipeptide(MDP) induced proliferation of thymocytes were tested after removal of macrophages by the selective binding of the MAb reactive cells to the plastic dish. Proliferation of the macrophage-deleted thymocytes was significantly suppressed, however, it was restored by addition of a small number of peritoneal macrophages. Those results strongly indicate that the MAb presented here is directed selectively to phagocytic cells of guinea pigs and should prove useful to study both in vivo and in vitro functions of the cells. PMID- 2258184 TI - Monoclonal antibodies identify new Toxoplasma gondii soluble antigens. AB - In order to characterize Toxoplasma gondii antigens, we have produced a panel of monoclonal antibodies specific for the parasite. A total of 22 hybridomas were derived from the spleen cells of mice immunized either with a 100,000 g supernatant of a sonicate from the RH strain (called F3), or chronically infected with the Wiktor or the 76K strain. Except for one hybridoma producing an IgM, all the hybridomas derived from mice immunized with F3 produced IgG1 antibodies while those obtained from chronically infected mice produced antibodies belonging to the IgG2b, IgG2a and IgM subclasses. Western-blot analysis showed that the panel of monoclonal antibodies defines at least 7 distinct antigens or antigen families. An antigen of apparent Mw 25 kD present exclusively in the 100,000 g supernatant of the T. gondii sonicate was recognized by the majority of monoclonal antibodies derived from mice immunized with the F3 fraction. Two other antigens of apparent Mw 27 kD and 29 kD present in the soluble and insoluble fractions of the sonicate were also identified. Monoclonal antibodies against the previously described 21 kD and 31 kD surface antigens and belonging to the IgG2a but also to the IgG1 subclasses were able to mediate lysis of the parasite in the presence of human non immune serum. The 22 monoclonal antibodies did not identify antigenic differences between the two independently isolated RH and Wiktor strains. PMID- 2258186 TI - Generation of monoclonal anti-digoxin antibodies. AB - Anti-digoxin monoclonal antibodies are a useful model for basic immunochemical studies, for investigation of endogenous digoxin-like substances and in immunoassay for cardiac glycosides. The complete phenotypic characterization is a requisite for the selection of antibodies with desired binding parameters for different purposes. Twenty-two high-affinity monoclonal antibodies specific for digoxin were obtained in two fusion experiments. Treatment of antigen-antibody complex with potassium thiocyanate (KSCN) and absorption ELISA were used for the selection of high-affinity antibodies at the earliest stages of hybridoma growth. The true affinity constants of selected antibodies were determined in ELISA. They had proven to vary between 10(-7) and 10(-10) M. The fine specificity of 21 anti digoxin monoclonal antibodies was determined by cross-reactivity experiments with 25 structurally related compounds. Cardiac glycosides, digoxin metabolites, endogenous steroids and spironolactone were used in the elucidation of the antigenic recognition pattern of antibodies. The elucidation of the binding characteristics of anti-digoxin monoclonal antibodies makes possible the selection of antibodies possessing binding characteristics appropriate for a wide range of designations. PMID- 2258185 TI - Comparison of monoclonal antibodies to estradiol obtained from structurally different immunogens. AB - The immunization procedure and immunogen characteristics required to optimize the production of anti-steroid monoclonal antibodies have been studied. Five different estradiol-bovine serum albumin conjugates were tested for immunizing mice, as were two different immunization protocols (high and low dose) and the effect of varying the myeloma/spleen cell ratio for cell fusion. Antibody producing hybridomas, obtained using the spleens of 9 high anti-steroid titre mice, were detected by RIA and EIA. The latter method was less specific than the former for higher affinity anti-estrogen antibodies. All the immunogens elicited anti-estrogen antibodies and the efficiency appeared related to the steroid density on the immunogen rather than the chemical nature of the derivative or the immunization and fusion protocols. Thirty-six anti-estrogen producing hybridomas were detected. Comparison showed that all the immunogens elicited antibodies in a wide range of affinities and specificities. None of the antibodies recognized corticosteroids or progesterone. Cross reactions with testosterone and other estrogens were not clearly related to the nature of the immunogen except that estradiol coupled to the BSA via its carbon 17 yielded antibodies specific for steroids with a non-derivatized phenolic A-ring. PMID- 2258187 TI - Spontaneous fusion between splenocytes and myeloma cells induced by bacterial immunization. AB - Spontaneous fusion between lymphoid and carcinoma cells in vivo has been described previously. Splenocytes from mice treated with LPS or mitogen have been reported to fuse better with myeloma cells using PEG as fusion agent than splenocytes from untreated mice. We report a phenomenon where immunization of mice with formalin treated, whole Haemophilus paragallinarum bacteria induced spontaneous fusion of splenocytes with myeloma cells in vitro, without the aid of any fusion agent. Co-immunization of mice with H. paragallinarum and an unrelated antigen (hen's egg white lysozyme), followed by co-culturing of the immune splenocytes with SP2/0 myeloma cells, yielded stable hybridoma cell lines producing anti-lysozyme antibodies. H. paragallinarum may be used in adjuvants to simplify the production of monoclonal antibodies, and the discovery of a promotional activity of a gram negative bacterium on cell fusion and hybridoma formation may shed new light on spontaneous fusion as a natural immune phenomenon in cancer. PMID- 2258188 TI - Lymphoid dendritic accessory cells of the rat. AB - The expression of MHC class II antigens on potential APC is a crucial step in T lymphocyte activation and the initiation of an immune response. The studies which are presented here were initiated to characterize the critical APC present in physiologically normal, untreated rats. Such a cell should constitutively express these antigens at high density and therefore provide the apparatus necessary to provoke both primary and secondary immune responses at any time. DAC were found to fulfill these criteria. In the absence of specific surface markers of rat DAC, the results are based on the strict combination of morphological appearance and functional activity. However, the high expression of MHC class II antigens may be regarded as semispecific markers for DAC which are distributed at strategic positions in many lymphoid and nonlymphoid tissues (Hart & Fabre 1981, Steiniger et al. 1984). The relatively low number of these cells observed in tissue sections and in in vitro isolates (0.1% of all cells) may explain their high activity as APC. This would facilitate the presentation of antigen in vivo to a sufficient number of competent T lymphocytes. DAC differentiate from a bone marrow progenitor cell pool preferentially under the influence of spleen cell derived activities. Although the exact lineage has not yet been determined it may be fair to speculate that DAC form a new cell lineage probably related to interdigitating cells but not to macrophages which differentiate from bone marrow derived precursors under the influence of colony-stimulating activities. However, the cooperation between DAC plus macrophages may provide the stage for T lymphocyte activation and T-T collaboration (Mitchison 1990). There are still many open questions concerning the general role of DAC in vivo and in vitro. To further characterize rat DAC, their tissue distribution, role in the immune response and possible influence on intrathymic lymphopoiesis, with respect to T lymphocyte subpopulations and the selection of the T-lymphocyte antigen-receptor repertoire, a panel of DAC-specific monoclonal antibodies must be generated in the future. Such antibodies will also be useful to study the mechanism by which DAC activate T lymphocytes. PMID- 2258189 TI - Antigen presentation in MHC class II transgenic mice: stimulation versus tolerization. PMID- 2258190 TI - Functional dichotomy between Langerhans cells that present antigen to naive and to memory/effector T lymphocytes. AB - The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Langerhans cells accomplish this important goal by their abilities to (a) activate naive T cells to antigens not previously encountered by the host, and (b) activate memory/effector T cells specific for previously encountered antigens. Arguments have been advanced to support the view that the functional properties of Langerhans cells used to present antigens to naive T cells differ substantially from the properties that equip Langerhans cells to activate effector T cells. The arguments are based in part on the fact that Langerhans cells carry out these functions in two very different environments: in the epidermis, and in the draining lymph node. The arguments are also based on results of in vitro experiments that reveal distinct differences in antigen processing and presenting properties of Langerhans cells freshly obtained from mouse and human skin as compared to Langerhans cells that have been cultured in vitro for 2-3 days. We propose that freshly explanted Langerhans cells faithfully reflect the functional program of intraepidermal Langerhans cells, and are able to present antigen to memory/effector T cells that enter the epidermal compartment. To accomplish this task, epidermal LC pick up environmental antigens, process them with great efficiency, and then present them in situ, without further upregulation of "accessory" signals (cell-adhesion molecules, secretion of additional cytokines). They can carry out this function, even in the presence of TGFB--a a cytokine which is constitutively made by keratinocytes, and which we have found to profoundly inhibit antigen presentation by most other types of "professional" antigen-presenting cells. Intraepidermal Langerhans cells are also capable of carrying cutaneous antigens through the dermal epidermal junction and migrating to the draining lymph node. We further propose that cultured Langerhans cells are fated to present antigens to unprimed/naive T cells, and thereby to initiate immune responses to new cutaneous antigens. Cultured LC process antigens less efficiently than fresh cells, but their unique capacity to present antigen effectively to unprimed T cells rests chiefly on the fact that they have significantly upregulated cell surface adhesion molecules, expression of MHC molecules, and secretion of activating cytokines--the "accessory" signals that are required for arousing naive T cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258191 TI - Follicular dendritic cells as accessory cells. PMID- 2258192 TI - The endothelial cell as a regulator of T-cell function. AB - These studies have analyzed the antigen-presenting capacities of EC. EC can transcribe, translate and express MHC class II molecules in response to IFN-gamma as well as express class I molecules. The class II dimeric structure is functional, in that allospecific CTL can efficiently kill IFN-gamma-treated EC or fibroblasts, an outcome that can be blocked by antibody to non-polymorphic regions of the class II molecule. Moreover, EC can present antigen in an MHC restricted manner to resting T cells as well as to antigen-specific cloned T-cell lines. This ability to stimulate primary as well as secondary responses has been further confirmed by experiments using purified populations of naive and memory T cells. In this regard, EC differ from fibroblasts and other non-immune cell types in that they possess costimulator activities necessary for activation of resting T cells. As the local concentration of IL-2 has been shown to be critical in determining the fate of T cells--whether they become activated or anergic--we have investigated the ability of EC to modulate T-cell IL-2 production, believing that this may underlie their ability to act as costimulatory cells. Using PHA stimulated peripheral blood mononuclear cells or purified CD4+ T cells we have found that EC can augment IL-2 production, typically by 3- to 8-fold. This increased IL-2 production is functional as OKT3-stimulated or sub-optimally PHA stimulated T cells proliferate more in the presence of EC than in their absence. The major pathway by which EC augment T-cell IL-2 production is cell contact dependent and involves the CD2:LFA-3 ligand pair. However, use of blocking mAb to CD2 and LFA-3, of PI-LFA-3, and of the immunosuppressive drug CsA has allowed us to reveal the presence of a second signalling pathway. This pathway confers a certain degree of CsA resistance on T cells, but the ligands involved have not yet been identified. We do not find a role for CD28, LFA-1:ICAM-1, VLA-4:VCAM-1 or CD44 in this system. Augmentation is independent of EC metabolism or soluble factors, as fixed cells are almost as efficient as living cells. Similar mechanisms seem also to be involved in more physiological settings, such as alloresponses. Here, proliferation can be blocked by antibodies to CD2 or LFA-3, presumably by blocking of augmented IL-2 production.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258193 TI - Heart transplantation. PMID- 2258195 TI - Mitral valve repair: encouraging trends. PMID- 2258194 TI - Mitral valve repair: techniques and results. AB - From January 1986 to December 1989, seventy patients underwent mitral valve repair. Sixty-four patients had severe mitral stenosis (MS) and mitral regurgitation (MR), while six patients had severe mitral regurgitation (MR) only. The technique used was a combination of posterior semicircular annuloplasty, mitral commissurotomy and chordal shortening. There were two operative deaths. All except three of the surviving patients are asymptomatic. There has been no episode of thromboembolism. One patient has required valve replacement and two others have had a revision of the repair in the follow up period. Predischarge and late (3 months to 3 years) echocardiography suggests that the repair is satisfactory. PMID- 2258196 TI - Comparison of atrial and VVI pacing modes in symptomatic sinus node dysfunction without associated tachyarrhythmias. AB - The natural course of patients with symptomatic sinus node dysfunction who did not have associated tachyarrhythmias before pacemaker implantation was compared after VVI and atrial pacemaker implantation. Between April 1981 and June 1989, forty-seven such patients (mean age 52 + 13 years) received VVI pacemakers and forty patients (mean age 54 + 13 years) received AAI or DDD pacemakers. Baseline clinical characteristics and severity of sinus node dysfunction were comparable in the two groups. Over a follow up of 10 to 96 months (mean 49.2 + 26 months), 11 (23.4%) VVI patients were in functional class II or more compared to 2 (5%) atrially paced patients (p less than 0.01). Other complication rates were also higher in the VVI group as compared to AAI group viz. atrial fibrillation (21.2% vs 2.5% p less than 0.01) and stroke (10.6% vs 2.5%) though the number of deaths (14.9% vs 10%) was not significantly different in the two groups. Two patients in atrial paced group and one patient in VVI group developed first degree heart block. There was no incidence of second or third degree heart block. Transient loss of atrial sensing occurred in 3 patients and atrial lead displacement in 2 cases, but overall incidence of lead related problems was low and comparable in both groups. Thus atrial pacing is superior to ventricular pacing in sinus node dysfunction and risk of developing high grade atrioventricular block on follow up is low. PMID- 2258197 TI - Two-dimensional and Doppler echocardiographic study of coronary arteriovenous fistulas. AB - Sixteen patients with coronary arteriovenous fistula (CAVF) were studied by two dimensional echocardiography (2DE). Of these 12 had Doppler studies. In all, the diagnosis of CAVF was confirmed by aortic root or selective coronary angiography. In 8 patients, the 2DE findings suggested CAVF. Five patients had dilated main coronary arteries and in 4 patients abnormal fistulous channels were identified. Two had diastolic flutter of the tricuspid valve and one had spontaneous contrast in the right atrium. In 11 out of 12 patients, Doppler analysis picked up a continuous flow (to the right atrium in 5, right ventricle in 4 and to both ventricles in 2 patients) prior to the cardiac catheterisation. We conclude that noninvasive diagnosis of CAVF can be made with the combined use of two dimensional and Doppler echocardiography in most of the patients. PMID- 2258198 TI - Profile of submitral left ventricular aneurysms in Indian patients. AB - Annular subvalvar aneurysms of the left ventricle initially described from Nigeria are considered to be rare in India. We report 6 such cases studied clinically and by noninvasive and invasive investigations during the last 8 years. In 4 cases morphologic documentation was available at surgery or autopsy. The clinical picture was dominated by congestive cardiac failure and mitral regurgitation and most of the patients were young. Echocardiographic studies provided the precise noninvasive diagnosis by demonstrating large aneurysms arising below the posterior mitral leaflet. In one case the submitral left ventricular aneurysm extended into the left atrium. The mortality was high in unoperated cases and operative repair under cardiopulmonary bypass is the most appropriate management. PMID- 2258199 TI - Taussig-Bing complex--a pathologic study of eight cases. AB - Taussig-Bing Complex, an uncommon anomaly, was found in 8 out of 110 hearts of double outlet right ventricle (7.2%). The mean age at death was 23.5 months with maximum survival upto 10 years. There was only one case of dextrocardia; viscero atrial and atrio-ventricular concordance was seen in all. Subpulmonary ventricular septal defect (VSD) was restrictive in two cases, in one of whom it was due to spontaneous closing process. Additional VSD was found in 2 cases. The great vessels showed side by side relationship with bilateral conii in 7 cases. In the remaining case there was L malposition with absent subpulmonary conus. Subpulmonary stenosis was noted in 3 cases. Tubular hypoplasia of aorta was seen in 2 cases with subaortic obstruction in one. Mitral valve abnormalities were present in 5 cases of which stenotic lesions were seen in 3. Coronary artery abnormalities were noted in 3 cases. PMID- 2258200 TI - Blood supply of the human interventricular septum in north-west Indians. AB - The blood supply of the human interventricular septum was studied in hearts obtained from 500 (300 males and 200 females) medicolegal autopsy subjects aged 18 to 75 years. In 350 specimens the coronary arteries were injected with 20 per cent solution of cellulose acetate butyrate and branches supplying the septum were displayed by dissection while in the remaining hearts the arteries were injected with a solution of barium sulphate and X-rays taken. The anterior two thirds of the septum is supplied by 4 to 10 perforators and one or two long septal arteries (in 94 per cent instances) which arise from the anterior interventricular artery; the latter turns round the inferior border of the heart and extends for a variable distance in the caudal part of the interventricular sulcus and supplies perforators to the posterior one-third of the septum. The cephalic part of the posterior one-third of the septum gets its blood supply from the posterior interventricular artery; some variations in this arrangement have been encountered. In about 85 per cent instances the right coronary artery or its conus branch gives an interventricular septal branch which pierces the anterior wall of the right ventricle and runs subendocardially on the supraventricular crest to reach the interventricular septum where it anastomoses with the anterior perforators; about 15 per cent subjects who do not have this septal branch are likely to sustain a larger infarction in case the anterior interventricular artery gets blocked. PMID- 2258201 TI - Dissociation of left ventricular end-ejection from end-systole: scintigraphic evaluation and implication. AB - We have measured the extent and evaluated afterload dependence of temporal dissociation of left ventricular end-ejection from end-systole using count rate dependent scintigraphic method. Good predictability of the dissociation (y) especially in the lower ranges of afterload (x) has been demonstrated (y = 9.1 x 763: r1 0.72: r2 0.55: r3 0.86). Role of the dissociation as the corrective parameter in count rate dependent scintigraphic method for evaluation of left ventricular contractile function (in contradistinction to the ejection function) has been discussed. PMID- 2258202 TI - Determinants of left ventricular function in isolated rheumatic mitral stenosis. AB - Left ventricular end-diastolic volume (preload), peak systolic wall stress (afterload), instant Emax (contractility index = peak systolic left ventricular pressure/end-systolic volume), left ventricular mass, left ventricular ejection fraction (LVEF) alone and normalised for mass index, were studied in 30 patients with isolated rheumatic mitral stenosis (group 1) and compared with 24 normal individuals (group II) who served as control. Preload was not different in the two groups (p = NS), afterload was increased in group I (p = 0.01), while LVEF, Emax, left ventricular mass and mass normalised LVEF were reduced in mitral stenosis as compared to normal control (p less than 0.01- less than 0.001). Comparison of patients with reduced ejection performance (LVEF less than 50%, n = 9, group IA) with those having normal LVEF (n = 21 group IB) revealed increased left ventricular end-diastolic volume and reduced left ventricular mass, mass normalised ejection fraction and Emax (in IA p less than 0.05). Peak systolic wall stress was comparable in these two subgroups. This study shows that the major determinant of left ventricular dysfunction in isolated rheumatic mitral stenosis is impaired contractility and not the loading factors. PMID- 2258203 TI - Systolic time intervals in rheumatic mitral stenosis. AB - Thirty two patients with pure mitral stenosis and twenty normal subjects were studied by M-Mode Echocardiography and systolic time intervals. Preejection period (PEP) was increased in 62 percent of patients in New York Heart Association (NYHA) Class III and IV, compared to 42.9 percent of cases in NYHA class I and II. Left ventricular ejection time (LVET) was abbreviated in 87.5 percent cases in NYHA class III and IV, and in 58.3 percent of cases in NYHA class I and II. PEP/LVET ratio was significantly increased (p less than 0.01) in mitral stenosis (0.42) compared to normal subjects (0.33) while calculated left ventricular ejection fraction (EF) was significantly lower (p less than 0.01) in mitral stenosis (60%) compared to normal subjects (71.55%). It is hypothesized that a rigid "mitral complex" immobilises the posterobasal area of the left ventricle in mitral stenosis thereby impairing left ventricular contraction. PMID- 2258204 TI - Profile of cardiac complications of snake bite. AB - The present study was conducted in 30 cases of snake bite to understand fully the intricacies of the cardiac profile and to render help in the management of the problem arising out of them. All were subjected to routine and specific investigations (ECG, X-ray Chest, SGOT). The present study concluded that 57 per cent of patients of snake bite were in 2nd and 3rd decades of life. Viperine snake bite occurred in 93 per cent and elapide snake bite in 7 per cent of cases. Cardiotoxicity was seen in only 25 per cent patients with viperine bite. Seventy six per cent of the patients presented within 24 hours of the bite. Seventy per cent of patients had haemorrhagic manifestations and 30 per cent had cardiotoxicity. The disturbance in heart rate was seen in 47 per cent, rhythm disturbance in 6.7 per cent, tachycardia in 36.7 per cent and bradycardia in 10 per cent cases. Hypertension was found in 6.7 per cent, hypotension in 16.7 per cent. Thirty per cent of patients had gallop rhythm and it persisted in 16.6 per cent patients till discharge. One patient had evidence of pulmonary edema and one had basal congestion. Cardiomegaly on chest X-ray was found in one patient and elevated SGOT titres were found in ten per cent. Common electrocardiographic changes were sinus tachycardia, sinus arrhythmia (6.6%), sinus bradycardia (10%), tall T-wave in V2 (3.3%), pattern suggestive of acute anterior wall infarction with reciprocal changes (3.3%), myocardial ischemia (10%), non-specific ST-T changes (16.7%) and atrioventricular block (3.3%). The mortality rate was 10 per cent and all these patients had bleeding manifestations and abnormal electrocardiograms. PMID- 2258205 TI - Inflammatory myocarditis presenting as acute myocardial infarction. AB - We present data of two patients with endomyocardial biopsy proven acute myocarditis presenting with clinical and electrocardiographic features of acute transmural myocardial infarction. Coronary angiograms were normal in both of them. The presentation of inflammatory myocarditis as myocardial infarction is emphasized. PMID- 2258206 TI - Prognostic significance of transient type II second degree atrioventricular block induced during exercise testing. AB - During exercise testing a 70 years old male developed Type II second degree AV block which reverted in recovery period. On follow up 3 months later, he developed symptomatic 2: 1 atrioventricular block and required permanent pacemaker implantation. PMID- 2258207 TI - Echocardiographic assessment of the size of aortic and pulmonary valve annulus before balloon valvoplasty. AB - Two dimensional echocardiographic measurements of the size of aortic and pulmonary valve annulus were made in 60 patients before balloon valvoplasty and compared to the angiographic measurements. Aortic valve annulus was measured in 34 patients (26 with valvar aortic stenosis and 8 with discrete subaortic stenosis) in the parasternal long axis or apical 5-chamber views. The pulmonary valve annulus was measured in 26 patients with valvar pulmonary stenosis (PS) in the parasternal short axis view of the right ventricular outflow view. The visualization of the annulus was good in all except 2 patients with valvar PS. Angiographic measurements of the aortic and pulmonary valve annulus were made in aortic root and right ventricular angiograms respectively, taken in both right and left anterior oblique views. There was an excellent correlation between the measurements of the annulus size by the two techniques (r value for pulmonary valve 0.91; for aortic valve 0.96; over all 0.94). Echocardiography can accurately measure valve annulus size and help in choosing balloon dilatation catheter of appropriate size before the valvoplasty procedure. PMID- 2258209 TI - Helicobacter pylori in its lair: a role in ulcer recurrence? PMID- 2258208 TI - Chronic atrial fibrillation reverting to sinus rhythm following thumpversion in a case of rheumatic heart disease. PMID- 2258210 TI - Isolation of Helicobacter pylori from dental plaques in healthy volunteers. AB - The presence of Helicobacter pylori (H pylori) was looked for in dental plaques of 40 healthy volunteers by CLO test, culture and smear stained with Warthin Starry stain. H pylori was found to be present in the dental plaques of all 40 volunteers. The dental plaque is an important reservoir of H pylori. PMID- 2258211 TI - Thoracic stomach: comparative evaluation of endoscopy, gastric aspirate analysis and hepatobiliary scintigraphy in the diagnosis of duodeno-gastric reflux. AB - Twenty patients with thoracic stomach were subjected to hepatobiliary scintigraphy for the diagnosis of duodenogastric reflux. The results of the radionuclide studies were correlated with those of endoscopy and biochemical estimation of total intragastric bile acid. Hepatobiliary scintigraphy was found to be more sensitive (91.6%) and accurate (95%) than endoscopy (25% and 55% respectively) and biochemical estimation of total intragastric bile acid content (66.6% and 80% respectively). Being noninvasive and physiological, radionuclide study appears suitable for routine clinical use in the diagnosis of duodeno gastric reflux. PMID- 2258212 TI - Management of foreign bodies in the upper gastrointestinal tract. AB - Records of 55 consecutive patients who had ingested foreign bodies were reviewed retrospectively. Foreign bodies were located in the esophagus, stomach and duodenum in 25, 27 and 3 patients respectively. Eleven of these passed through the entire gastrointestinal tract spontaneously and uneventfully. Endoscopic extraction was successful in 36 patients while 8 needed surgical removal of the ingested object. Only one death was encountered. We conclude that using simple guidelines, foreign body ingestion can be managed with a low incidence of complications and mortality. PMID- 2258213 TI - Primary ascaridial perforations of small intestine and Meckel's diverticulum. AB - The clinical presentation of six cases with primary ascaridial perforations of the terminal ileum (4 cases) and Meckel's diverticulum (2 cases), without any associated underlying intestinal disease, is described. All the cases presented clinically as peritonitis and had worm masses in the intestinal lumen with maximal impaction in the terminal ileum. Ileal perforations were surgically closed in two layers after removal of the worms. Diverticulectomy after removal of the worms was performed for Meckelian diverticular perforations. Peritoneal toilet was done in all the cases. Pressure necrosis from the impacted worm masses probably resulted in these perforations. PMID- 2258214 TI - Immunogenicity of yeast-derived hepatitis B vaccine in Pakistani adults. AB - A study of the immunogenicity and safety of 20 micrograms recombinant DNA yeast derived hepatitis B vaccine was conducted in 153 Pakistani adults. All participants were in good physical condition, had negative hepatitis B serological markers (HBsAg, anti-HBs, anti-HBc) and normal ALT. Anti-HBs developed in 33%, 81% and 98% of subjects one month after the first, second and third dose respectively. Minor systemic and local side-effects were observed in 39% of individuals. We conclude that yeast derived hepatitis B vaccine is safe, effective and immunogenic in Pakistani adults. PMID- 2258215 TI - Gastrointestinal bleeding in malaria. AB - Hematological alterations are frequent in patients with malaria. However, these rarely manifest clinically, except for symptoms due to anemia. Two cases with gastrointestinal hemorrhage as a complication of malaria are reported. PMID- 2258216 TI - Gastric metastases from esophageal cancer. AB - Gastric metastases from esophageal cancer are seldom diagnosed antemortem. Two patients who had endoscopically detected gastric metastases from esophageal cancer are reported. One patient had a metastasis developing 6 months after radiation therapy; the other developed metastasis after surgical resection of the primary tumor. PMID- 2258217 TI - Gastric carcinoma in a child associated with nodular lymphoid hyperplasia of the colon. AB - We report a 12 year old boy of Nepalese origin with gastric adenocarcinoma and associated nodular lymphoid hyperplasia of the colon, with hemoglobin E trait and normal serum immunoglobulins. The boy underwent a curative resection and is free of recurrence or metastasis nine months after diagnosis. PMID- 2258218 TI - Primary sclerosing cholangitis with chronic pancreatitis. AB - We report a patient with primary sclerosing cholangitis and associated pancreatitis. She had exocrine and endocrine pancreatic insufficiency. PMID- 2258219 TI - Tc-99m human serum albumin abdominal scanning in protein-losing enteropathy. PMID- 2258220 TI - Spontaneous perforation of the left hepatic duct with acalculous cholecystitis. AB - Spontaneous rupture of the biliary tree leading to bile peritonitis is rare. We report a boy who developed spontaneous perforation of the left hepatic duct and had acalculous cholecystitis. PMID- 2258221 TI - Management of biliary ascariasis in children. PMID- 2258222 TI - Prevalence of Helicobacter pylori in symptomatic patients undergoing gastrointestinal endoscopy. PMID- 2258223 TI - Cholecystectomy with and without drainage. PMID- 2258224 TI - [Implantology applications in adult orthodontics]. PMID- 2258226 TI - [Dentomaxillary radiological imaging from conventional to numeric. Numerization of radiograms. Storage, pseudo-color conversion]. PMID- 2258225 TI - [Clinical evaluation of Parogencyl in gingivorrhagias]. PMID- 2258227 TI - [Condylar slope. "Quick-axis" graphic registration for programming of articulators]. PMID- 2258228 TI - [Prepared packets]. PMID- 2258229 TI - [Indications and advantages of gingival flange in fixed prosthetics. A new technique]. PMID- 2258230 TI - [Clinical evaluation of the effect of 2 high fluoride content dentifrices on dentin hypersensitivity]. PMID- 2258231 TI - [Simplification test in the choice of impression techniques for removable partial dentures]. PMID- 2258232 TI - [RC Prep and immediate endodontic obturation]. PMID- 2258233 TI - [Microscopic analysis of the dentition of Isabella, Duchess of Aragon]. PMID- 2258234 TI - [Treatment of the periodontal abscess]. PMID- 2258235 TI - [Information needs of dentists on radiological and nuclear risks]. PMID- 2258236 TI - Grandparents and adult grandchildren: what do they do for one another? AB - This article reports findings from a study in which the functional exchange of services, emotional (expressive) and tangible (instrumental) between grandparents and adult grandchildren were examined. The reciprocal (equivalent) and nonreciprocal (excessive giving or receiving) exchange of services was measured by the frequency of exchange and perception of potential support between the dyad. Noninstitutionalized Jewish grandparents (118, 65+ years of age) with at least one adult grandchild (18+ years of age) were randomly selected from an apartment house in Miami Beach. The results showed that the majority of grandparent-adult grandchild relationships are not reciprocal in either expressive or instrumental support. Grandparents' perception of reciprocity is that they receive more than they give. Social-work knowledge of functional exchange between this dyad may strengthen the social-support network of the elderly. PMID- 2258237 TI - Anaphor comprehension in younger and older adults. AB - This research was aimed at evaluating adult age differences in language comprehension, which has been hypothesized to decline in normal older adults. Three experiments were conducted to investigate the comprehension rate of pairs of related sentences. In Experiment 1, the related material consisted of either terms repeated from the first sentence or terms associatively related to the antecedent. In Experiment 2, the generality of the antecedent term in the sentence pairs varied, as did its typicality. In both experiments, young-old (age 55-69) and old-old (age 70-87) adults read the target sentences in the pairs more slowly than did young adults (age 20-36); age, however, did not interact with the condition. Experiment 3 repeated the conditions of Experiment 2, but, since only one sentence at a time was visible during a trial, the participants had to remember the first sentence while reading the target sentence. Young participants (aged 20-35) showed the same treatment effects as in Experiment 2, but the old (aged 55-86) showed deficits in online comprehension. The results of the three experiments suggest that the speed of comprehension processes required to match related terms in sentence pairs are not impaired with age as long as they do not have to be remembered. PMID- 2258238 TI - Self-perceptions of life-span gender-role development. AB - This article discusses two studies in which participants reported on self perceptions of life-span gender-role variability based upon their expected or past performance in normative age-related developmental tasks. In Study 1, students rated themselves on the Personal Attributes Questionnaire (PAQ) at the present time and in two prospective tasks (parenthood and retirement). In Study 2, retired adults completed the PAQ at the present time and in two retrospective tasks (work-entry and parenthood). Both studies showed that participants perceived their masculine and feminine gender-role attributes as varying significantly as a result of the function of the three rating contexts, and both masculinity and femininity were perceived to increase from the chronologically earliest of these tasks to the latest. PMID- 2258239 TI - Personality trait correlates of attitudes toward older people. AB - The objective of this study is to determine whether personality is related to attitudes toward older people. To address this question, a sample of 228 students and gerontology practitioners completed the Aging Opinion Survey, the Cattell 16 Personality Factors Test, and a demographic questionnaire. When the influence of age, sex, education, and social desirability are controlled, a constellation of personality traits remains significantly related to attitudes toward older people. Specific trait-attitude correlations are described, and traits related to positive attitudes toward older people are shown to fit within three personality groupings: low anxiety traits, sensitive-intuition traits, and intellectual ability. These traits combined with demographic variables account for up to 30 percent of the variance in attitudes toward older people. The results of this study indicate that personality traits are clearly related to attitudes toward older people. PMID- 2258240 TI - Youthful ideas about old age: an analysis of children's drawings. AB - Youthful ideas about old age are investigated by means of an analysis of children's drawings of young and old people. The age of the artists ranged between ten and a half years and eleven and a half years of age, and each artist drew four pictures (a young woman, an old woman, a young man, and an old man). Analyses consisted of a content analysis of drawings; the calculation of standard scores by means of the Harris-Goodenough Draw-A-Person (DAP) test scoring procedure (in order to effect comparisons of scores within each child's corpus of drawings); and measurement of the height of each drawing. The content analysis suggested a greater degree of stereotyping in boys' pictures of young women and in girls' pictures of old men than in other drawings. Pictures of old people overall were no more stereotyped than were those of young people, though they were more negative in content. Results of the DAP standard score calculation comparisons found consistent differences between children's drawings of old and young people, with pictures of old people attaining lower standard scores than those of young people. Size measurements revealed pictures of old people to be significantly smaller than those of young people. Explanations for these differences are discussed and further investigations recommended involving a wider population of artists and focusing particularly on the size of drawings. PMID- 2258241 TI - Vickie Lorene Rock, petitioner v. Arkansas on writ of certiorari to the Supreme Court of Arkansas [June 22, 1987]. PMID- 2258242 TI - Rock v. Arkansas: a critique. AB - Rock v. Arkansas is the first United States Supreme Court decision that addresses the conflict between a criminal defendant's right to testify in his or her own behalf and a state's right to impose a restrictive rule of evidence barring hypnotically refreshed testimony. The present critique describes the operative facts in Rock v. Arkansas and the majority and minority decisions. It also highlights some of the psychological and legal issues involved and speculates on what Rock v. Arkansas may portend for the broader issue of the admissibility of hypnotically refreshed testimony in general. PMID- 2258243 TI - Rock v. Arkansas: hypnosis, the defendant's privilege. AB - In Rock v. Arkansas (1987) the United States Supreme Court ruled in a 5 to 4 decision that the constitutional rights of defendants to testify on their own behalf take precedence over whatever state rules exist regarding exclusion of hypnotically refreshed testimony. The problem of denying defendants their constitutional rights was the reason we have argued that defendants' hypnotically refreshed testimony should generally be permitted, whereas the unreliability of hypnotically elicited memories and the manner in which hypnosis diminishes the effectiveness of cross-examination make the general exclusion of testimony from hypnotized witnesses essential (M. T. Orne, 1982). We discuss the Rock case, as well as the majority and minority opinions expressed by the United States Supreme Court, and offer reasons why a bifurcated standard--one that admits hypnotically refreshed testimony from defendants and excludes it from witnesses--is consistent both with the Court's ruling and with the scientific evidence regarding the use of hypnosis, as well as being an appropriately fair way in which to protect the constitutional rights of the defendant and the state. PMID- 2258244 TI - Hypnosis with a criminal defendant and a crime witness: two recent related cases. AB - 2 legal cases involving hypnosis have recently been adjudicated by American courts. In Rock v. Arkansas (1987), the United States Supreme Court ruled that the hypnotically elicited testimony of a criminal defendant was admissible in court. This decision was grounded upon the constitutional right of a defendant both to testify, and to call witnesses, on his or her own behalf. Shortly afterwards, citing Rock as a precedent, a Texas Court of Appeals admitted the hypnotically elicited testimony of an eyewitness in Zani v. State (1988), on the grounds that it would be unfair to admit the hypnotically elicited testimony of defendants, and proscribe it for victims and witnesses. It is not clear what effect this doctrine of equity will have upon other North American court cases that involve hypnosis. PMID- 2258245 TI - Sexual abuse and the abuse of hypnosis in the therapeutic relationship. AB - In The Netherlands, individuals charged with rape may be prosecuted only in instances in which the suspect could have known that the victim was unconscious or in a state of powerlessness. Hypnosis might be looked upon as a method by which an unscrupulous person could sustain such a state of powerlessness in a victim. As an expert witness, the present author participated in a court case against a lay hypnotist who was accused of abusing 9 women. The methods and strategy used by the lay hypnotist are presented as well as are the diverse reactions of the women involved in the case. Feelings of nonvolition appear to have been a relevant factor in the coercion, especially in women who demonstrated hypnotic phenomena such as arm levitation, catalepsy, etc. The basis for sexual coercion was established only after the interpersonal relationship had been redefined as a therapeutic relationship. Introduction within the pseudotherapeutic relationship of a sexual rationale for the presented complaints helped to provide a framework for actual sexual acts to occur. With certain individual patients, the introduction of hypnosis enhanced the subjective experience of nonvolition and with it the vulnerability for abuse. It may be hypothesized that patients with a tendency for external attribution and high hypnotizability are specifically at risk for this kind of abuse when hypnosis is used in the context of a therapeutic relationship. PMID- 2258246 TI - Dissociative phenomena and the question of responsibility. AB - There are many controversies regarding the prevalence, causation, possible iatrogenicity, and treatment of multiple personality disorder. Those who view the disorder as much more prevalent than has previously been suspected believe it is caused by experiences of severe child abuse and have used rather unorthodox techniques to help the patient relate the experience of abuse to current problems of dissociation. Other clinicians believe the disorder is overdiagnosed and that it may be created or made worse by therapists who unwittingly reinforce symptoms of dissociation. Many of the controversies about these issues can be clarified by considering the manner in which clinicians attribute responsibility for undesirable conduct associated with the disorder. In dealing with multiple personality patients, clinicians regularly must decide whether their therapeutic approach will emphasize the patient's responsibility for undesirable conduct or will minimize it. Practical and theoretical arguments can be made for both approaches. There are important consequences to patients using either approach, and particularly harmful consequences with inconsistent approaches. Clinical experience and wisdom dictate that until we have more objective data about the results of various forms of treatment, the preferred method of treatment of multiple personality patients should continue to focus upon maximizing their responsibility for any type of undesirable conduct. PMID- 2258247 TI - Potential jurors' opinions on the effects of hypnosis on eyewitness identification: a brief communication. AB - The present study examined a selected group of potential jurors' opinions on the effects of hypnosis on eyewitness identification and testimony. A group of 78 undergraduate psychology and optometry students completed a 2-part multiple choice questionnaire. The first part assessed Ss' knowledge of several issues concerning eyewitness testimony. The second part of the questionnaire contained 11 items which assessed Ss' beliefs and expectations concerning the effects of hypnosis on eyewitness identification and testimony. It was found that Ss' opinions on the effects of hypnosis on eyewitness testimony and identification were at odds with current empirical findings. These results, in accord with the previous literature, suggest that it is imperative that the courts be informed of the use of hypnosis during police work and that adequate precautions be taken to avoid a potential source of miscarriage of justice. PMID- 2258248 TI - Activation of renin-angiotensin system does not cause skeletal muscle cramps during hemodialysis. AB - Activation of the renin-angiotensin system usually occurs during hemodialysis and in hemodialyzed normal dogs parallels reductions in blood flow to a tissue group that is largely composed of skeletal muscle. To determine if excessive activation of this system might cause dialysis-associated skeletal muscle cramps in some patients, we conducted a double-blind, randomized and balanced trial in which 5 patients with frequent dialysis-associated cramps were each given either a 25 mg oral dose of captopril or placebo 1 h before 8 consecutive dialyses. Captopril increased the frequency of dialyses complicated by skeletal muscle cramps in 1 patient and did not affect cramp frequency in the other 4 patients. Predialysis plasma renin activity (PRA) averaged 3.9 ng/ml/h (+/- SD) and was the same as in unselected hemodialysis patients. Following captopril, PRA increased by an average of 2.2 +/- 0.7 times, similar to the 2.6-fold increase that was reported when this drug was used to prevent dialysis-associated hypertensive crises. However, hemodialysis by itself did not activate the renin-angiotensin system as consistently in patients with frequent dialysis-associated skeletal muscle cramps as in unselected hemodialysis patients and the ratio of post- to predialysis PRA averaged 1.0 +/- 0.6. We conclude that the renin-angiotensin system does not mediate, and that its activation during hemodialysis may actually help prevent, dialysis-associated skeletal muscle cramps. PMID- 2258249 TI - Hypertension and arrhythmias: effects of slow-release nicardipine vs chlorthalidone: a double-blind crossover study. AB - The aim of the study was to compare the effect of slow-release (SR) nicardipine, placebo and chlorthalidone on hypertension-related arrhythmias evaluating 24-h ambulatory ECG. After a 2-week placebo run-in, the patients were randomized according to a double-blind design and treated with either SR nicardipine (40 mg b.i.d.) or chlorthalidone (25 mg once daily) for 8 weeks. At the end of this period, the patients were again treated with placebo for an additional 2 weeks and then crossed over and treated with either SR nicardipine or chlorthalidone for another 8 weeks. Three patients were withdrawn from the study at the end of the first period (1 after SR nicardipine and 2 after chlorthalidone) because of severe arrhythmias (Lown's class 4B) requiring antiarrhythmic therapy. The statistical evaluation was performed on data from 36 patients. SR nicardipine and chlorthalidone determined a significant reduction of both systolic and diastolic BP, with greater decrease with SR nicardipine and without modification of HR. Twenty-four-h ambulatory ECG showed a reduction of both supraventricular and ventricular arrhythmias by SR nicardipine not only compared to placebo but also vs chlorthalidone. Similarly, the severity of ventricular arrhythmias, according to Lown's classes, was reduced only after SR nicardipine. These results were confirmed also dividing the patients according to echocardiographic criteria of LVH. The adverse effects were slight and well tolerated with both drugs. Among hematochemical data, only chlorthalidone induced significant reduction of blood potassium (with 3 cases of hypokalemia). In conclusion, SR nicardipine was found to be more efficacious than chlorthalidone in controlling not only BP but also the arrhythmic events related to hypertension. PMID- 2258250 TI - A clinical trial comparing a new NSAID (droxicam) and piroxicam in spinal osteoarthritis. AB - This double-blind, parallel, controlled and randomized trial compares the clinical efficacy and tolerance of a new NSAID (pro-drug of piroxicam), droxicam, at the dose of 20 mg/day against that of piroxicam at the same dose. The comparison is drawn after the administration to 30 patients with spinal osteoarthritis during 8 weeks after a single-blind placebo-period run-in of 7 days. Results show that both drugs improve, with statistical significance, all parameters evaluated (pain intensity, morning stiffness, nocturnal pain, pain after getting up and after 30 min standing, difficulty in daily living, frequency of pain exacerbations and the ability to do several daily activities). No statistically significant differences were found between groups. Only one case in the droxicam group and two in the piroxicam group reported subjective complaints of mild intensity that did not require additional treatment or interruption of the study. PMID- 2258251 TI - Acetylator phenotype in patients with allergic diseases and its clinical significance. AB - The genetic polymorphism of drug acetylation rate in man is an important determinant of the toxic and therapeutic response to certain drugs. This polymorphism can alter not only drug effects but may be a factor influencing the frequency of the occurrence of some disease states. The aim of our study was to establish whether there exists any correlation between the acetylator phenotype and the development of allergic diseases. In patients with allergic diseases and in healthy persons as a control group, the acetylation phenotype was determined by the sulfadimidinic method. In the group of patients with allergic diseases without infectional factor 76% slow and 24% rapid acetylators were found. This predominance of slow acetylators was statistically significant (by using chi 2 test) with comparison to the group of healthy persons, where 49% slow and 51% rapid acetylators were observed. Considerable predominance of slow acetylators in patients with allergic diseases suggest that phenotype of slow acetylation may be a factor playing some role in pathogenesis of allergic diseases and may be a factor predisposing to the development of these diseases. PMID- 2258252 TI - Influence of alcohol consumption on erythromycin ethylsuccinate kinetics. AB - The effect of ethyl alcohol ingestion on erythromycin kinetics was studied. Nine healthy volunteers, four males and five females, participated in the study. They received, in two separate occasions, 500 mg of erythromycin ethylsuccinate ester given with water or with an alcoholic beverage. The antibiotic was assayed in plasma, using a microbiological method. Absorption and disposition parameters were calculated according to classical pharmacokinetic techniques. A longer lag time and a decrease in AUC were observed when the antibiotic was given with alcohol. The differences were statistically significant. It is likely that the effect of alcohol on gastric emptying could be responsible for the delayed absorption of the antibiotic. PMID- 2258253 TI - Pharmacokinetics of cefroxadine after infusion to healthy volunteers. AB - The pharmacokinetics of cefroxadine in healthy human volunteers was studied in plasma and urine, after an infusion administration of 1 g of this drug for 0.5 h. Blood and urine samples were microbiologically quantified by diffusion on solid gelose using Bacillus Subtilis ATCC 6633 as the test organism. Plasma and urine profiles were fitted to a reduced two-compartment model not having inactivating biotransformation as a route of elimination. The parameters of distribution for this model show a rapid disposition (t1/2 alpha = 0.28 h) and an average volume of the central compartment of 0.15 +/- 0.04 l/kg (range 0.20-0.09). The dominant terminal half-life (beta-phase) was 1.17 +/- 0.26 h (range 0.90-1.67). The total body volume 0.41 +/- 0.09 l/kg (range 0.30-0.52) indicates that there is no diffusion of the antibiotic into intracellular fluids of poorly perfused tissues due to its high elimination rate. PMID- 2258254 TI - Effects of food intake and meal size on the bioavailability of sulpiride in two dosage forms. AB - This study examined the influences of food intake on sulpiride (100 mg) bioavailability from a commercial film-coated tablet and of the meal size (small, medium or large) on sulpiride bioavailability from an aqueous solution in three healthy male volunteers. The cumulative urinary excretions of sulpiride for 48 h (Du48) from two dosage forms following oral administration were decreased approximately 30% by food intake. Also, a good correlation was found between the bioavailability of sulpiride from the solution and size of meals with the same dietary components. These results suggest that food intake and meal size before dosing significantly affect the gastrointestinal absorption of sulpiride. PMID- 2258255 TI - The influence of benzbromarone and its combination with hydrochlorothiazide on renal excretion of uric acid and electrolytes. AB - The results of a study investigating the effect of single oral administration of B (benzbromarone), and a combination of B + H (hydrochlorothiazide), in 10 healthy volunteers suggest the following conclusions: 1) In agreement with literary data, B at a dose of 100 mg has a significant hypouricemic effect with a 39% decrease after 6 h, and a 53% decrease after 24 h. 2) B and B + H significantly enhance renal clearance and fractional excretion of uric acid but there was no demonstrable significant inverse relation between these parameters and the plasma level of uric acid. 3) B affects PUA (plasma concentration of uric acid) also by some extrarenal action which is not related to the pre-existing alteration of uric acid metabolism. 4) Simultaneous single administration of B + H does not reduce the effect of B on renal excretion and on the plasma level of uric acid. 5) A single dose of B causes a slight but significant decrease in fractional potassium excretion without any demonstrable effect on fractional excretion of sodium and that of all osmotically active substances. PMID- 2258256 TI - Perceived consequences associated with the use of beer, wine, distilled spirits, and wine coolers. AB - Based on a national probability sample of 2,401 Americans aged 21 and over (1,069 of whom were deemed "drinkers" on the basis of having drunk at least one alcoholic beverage in the past 7 days), this study examines which of six specific problems people associate with the use of beer, distilled spirits, wine, and wine coolers. It was found that people are most likely to associate alcoholism, birth defects, drunk driving, and fighting and rowdy behavior equally with these four types of alcohol. But when beverage associations are made, distilled spirits and beer are blamed most frequently for these problems, whereas wine and wine coolers are virtually never thought of as being closely related to any of the problems under study. It was also determined that nearly 1 out of every 7 drinkers surveyed stated that birth defects are unrelated to alcohol use of any kind. PMID- 2258257 TI - The validity of self-reported abstinence and quality sobriety following chemical dependency treatment. AB - The validity of self-reports from 171 former patients at a 28-day inpatient treatment program was examined by comparing self-report measures of abstinence and current life functioning with concurrent reports by significant others. Strong convergent validation was found, with 92% of significant others agreeing with the self-reports of the former clients. The "quality of sobriety" measures of familial, occupational, social, and emotional adjustment were studied and validated by the convergent validation technique. Discussed is the value of convergent validation in terms of both follow-up success rates and program evaluation. Methodological concerns and resulting limitations of the data are reviewed. PMID- 2258258 TI - Religious values and beliefs and place of residence as predictors of alcohol use among Chinese college students in Singapore. AB - Data drawn from a detailed study of alcohol use among Chinese undergraduate college students in Singapore (N = 767) show identification with religious values and beliefs not to be a significant factor in terms of students' alcohol use. Students' place of residence (i.e., on campus in a hostel or off campus) was found to predict alcohol use but in a way opposite to the pattern commonly predicted - that is, students on campus tend to drink less than their off-campus counterparts. When religious values and beliefs identification as well as place of residence were examined together, it appears that these two factors have no influence on students' alcohol use. PMID- 2258259 TI - Predicting marijuana use among adolescents. AB - The present paper (1) contrasts the prevalence of marijuana use and involvement with marijuana among 194 delinquent and 405 nondelinquent adolescents, (2) examines the utility of an expanded version of Jessor and Jessor's (1977) problem behavior model in predicting adolescent marijuana use, and (3) tests the relative importance of the predictors of marijuana use. Personality variables that were added to the Jessor problem behavior model included: (1) stimulus reducing - augmenting, (2) ego strength, (3) anxiety, and (4) field dependence. Results showed that delinquents reported using marijuana more often than nondelinquents. In the multiple regression analyses the expanded model explained a slightly greater percentage of the variance in adolescent marijuana use than the Jessor and Jessor model. Of the added personality variables, the Vando (1969) Reducer- Augmenter dimension seemed to be a particularly significant predictor. In addition, reducing--augmenting seemed to be a better predictor of involvement with marijuana than several previously used personality and demographic variables since it replaced these in the final regression equation. Perceived environment variables measuring pressure from friends to use marijuana and friends as models for marijuana use were the best predictors of marijuana use. PMID- 2258261 TI - The social epidemiology of international drug trafficking: comparison of source of supply and distribution networks. AB - A variety of strategies have been implemented in an attempt to limit or prevent drug trafficking. Efforts have focused on reducing the supply of drugs, but they have not been very effective. There has been a shift recently to demand-reduction activities, but it is uncertain whether this approach will prove to be valuable. Most of the strategies that are employed are based upon the law enforcement approach. Alternative perspectives, based on principles of epidemiology and social network analysis, are presented and discussed in the context of studying drug trafficking on a global scale. More research and better sources of data and information are needed to delineate the relationship between availability and use, so that we might more effectively focus prevention activities. PMID- 2258260 TI - Prediction of risk for drug use in high school students. AB - On the basis of questionnaires administered to almost 2,000 high school students in Cali, Colombia, a subset of items was selected that deal primarily with parent -child relationships. This 53-item set, referred to as the Drug Risk Scale (DRS), was administered to two new cross-validation samples, one consisting of high school students and the other consisting of drug addicts attending drug rehabilitation centers. Significant differences in parent--child relations were found between these new groups. The DRS was also found to have reasonably high sensitivity and specificity. Its potential value as a risk-prediction instrument is discussed. PMID- 2258262 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2258263 TI - Breast-cancer etiology. Report of a working party for the Nordic Cancer Union. PMID- 2258264 TI - Mutations in human breast cancer cells: dominantly-acting oncogenes and tumor suppressor genes suggest strategies for targeted interference. PMID- 2258265 TI - Molecular lesions in breast cancer. PMID- 2258266 TI - Biology and natural history of breast cancer. PMID- 2258267 TI - Human breast-cancer growth and progression: role of secreted polypeptide growth factors. PMID- 2258268 TI - Steroids and steroid receptors in growth control of cultured breast cancer cells. PMID- 2258269 TI - Reduced breast-cancer mortality with mammography screening--an assessment of currently available data. PMID- 2258270 TI - Assessing low-risk agents for lung cancer: methodological aspects. Proceedings of an international workshop. Clearwater, Florida, 10-14 October, 1989. PMID- 2258271 TI - Environmental contaminants and low-level cancer risks: perceptions and scientific strategies. AB - Scientific and public perceptions concerning low-level lung cancer risks may vary. Recently the public has been more convinced of causal links between low level risk agents and cancer, and more interested in prevention of environmental exposures, especially those induced by others. Thus, scientific strategy is partly driven by the public need to resolve issues concerning the importance of low-level exposures and risks. Further, investigators have been challenged intellectually to create methodologies in order to study some of these relationships further, and scientific curiosity has been stimulated by the difficulties of pursuing such investigations. The importance of host characteristics, including the genetic bases of susceptibility, has become a major theme. Likewise, host behaviour has become a potential positive factor (e.g. diet) as well as a negative factor in the risk model for low-level agents. This paper discusses some of the information available on low-level agents and some of the methodological issues involved in studying them. The importance of measuring exposure as well as response is stressed, especially multi-pollutant exposures and interactions with host behaviour. PMID- 2258272 TI - Worldwide epidemiological patterns of lung cancer in nonsmokers. AB - A review of published reports on lung cancer was done to describe its worldwide epidemiological pattern and to elucidate the contribution of smoking and nonsmoking risk factors in its aetiology. Among lung cancer patients, roughly 98% of males worldwide, and 70-90% of European and American females, reported a history of smoking. Asian women had much lower (6-57%) rates of smoking. Mortality rates among female nonsmokers showed about a four-fold difference, being lowest in India and Japan, intermediate in the USA, and highest among the Chinese. There was some indication that incidence rates among nonsmokers may have increased in some societies in this century. The usefulness of histological comparisons among nonsmokers seemed limited since its distribution did not vary by place or ethnicity; about 70% were adenocarcinomas. In Western populations, younger lung cancer patients were more likely to have been smokers, whereas the opposite was true in Asian populations. Thus the epidemiological patterns of lung cancer in Western and non-Western societies are likely to be different, with nonsmoking risk factors being more important among women in general, and Asian women in particular. PMID- 2258273 TI - Interactions of xenobiotics in the respiratory tract following non-inhalation routes of exposure. AB - Compounds of highly variable structure may induce toxic effects and tumours in the respiratory tract following peroral or parenteral administration in experimental animals. Such compounds are used in industrial processes or may be present in the food as contaminants or pesticide residues. This review gives examples of selective metabolism and toxicity of chemicals in different segments of the respiratory tract. Many of these compounds require metabolic activation to exert toxicity. Accordingly, the susceptibility of the respiratory tract to the effects of such agents may be influenced by other compounds modulating the activity of activating xenobiotic metabolizing enzymes. Dietary factors may alter the susceptibility to experimental lung carcinogenesis also via other mechanisms. As concluded from experimental data, the human lung may be exposed to a wide array of potentially toxic compounds present in the diet or the environment. Such exposures may constitute confounding factors in low-risk lung cancer epidemiology. PMID- 2258274 TI - Protective dietary factors and lung cancer. AB - Since the first report of a protective effect of dietary vitamin A on lung cancer risk was issued in 1975, a succession of retrospective (case-control) and prospective (cohort) epidemiological studies have examined the association. Food frequency questionnaires have been used to assess dietary intake of food groups and to generate indices of specific dietary components, in particular retinol and carotene. Serum levels of retinol, carotenoids, and other micronutrients have been determined as well, and related to risk of lung cancer. The dietary studies have been notably consistent, finding an approximate 50% reduction in risk associated with high compared to low consumption of carotene-containing fruits and vegetables. Unresolved issues include gender differences, histological specificity and the interaction with cigarette smoking as well as the role of other possible protective factors found in these foods--indoles, vitamin C, trace minerals. Most studies in which serum beta-carotene was assayed in prospectively collected blood samples have found lower levels of beta-carotene in people who subsequently developed lung cancer. Unlike carotene, blood retinol levels do not reflect dietary intake under normal conditions and, as might be expected, have failed to show a consistent relation with risk of lung cancer. Although epidemiological studies have not strongly supported the role of preformed retinol as a protective agent, animal studies have provided convincing evidence that retinol and synthetic retinoids are protective against epithelial tumours including those of the lung. A number of on-going clinical trials are testing the efficacy of retinol, beta-carotene, synthetic retinoids and alpha-tocopherol for preventing cancer of the lung, especially in high risk groups such as heavy smokers, miners and asbestos workers. It is hoped that these trials will help explain the nature of the observed protective effect of fruit and vegetables. PMID- 2258275 TI - Methodological issues in the epidemiological investigations of lung cancer related to low-level risks. AB - There are several major issues that create great difficulties in the study of low level risks for lung cancer. Further attention needs to be addressed to the difficulties in design, ascertainment, classification, confounding and analysis found in the environmental epidemiological aspects of the investigation. Host predisposition is an important factor that requires further characterization in the process of conducting these environmental epidemiological investigations. Within the exposure assessment aspects of these investigations, major difficulties arise from the need to obtain total exposure estimates, dose estimates and in evaluating the interactions of the several pollutants of concern in exposure settings of interest. Low-level risks for lung cancer imply difficulties in the assessment of exposure-dose pattern. Further, bio-markers are needed to focus more on dose. Further, low-level risk ratios produce difficulties in distinguishing the effects of confounders. In order to facilitate further studies of lung cancer related to low-level risks, we will have to create new, more specific, and more efficient study designs. These studies will require much better exposure assessment and case ascertainment than typical of previous studies, and more complete measurement of confounders. PMID- 2258276 TI - Epidemiological issues in weak associations. PMID- 2258277 TI - Exposure analysis and assessment for low-risk cancer agents. AB - The analysis of exposure is a necessary feature of epidemiological studies. In the case of low-risk cancer agents, the examination of potential exposure should follow a sequence that prioritizes the major media and routes of concern. This will minimize the misclassification of exposure and the failure to identify important co-factors, e.g. contamination in other media, etc. The manuscript describes specific components of exposure analysis and provides examples that pertain to single and multimedia exposure problems. The approach is examined by using the Total Human Environmental Exposure Study (THEES) for benzo(a)pyrene as a potential model for low-risk cancer agents. Since benzo(a)pyrene can be found in air, water, soil and food, and has a number of sources, THEES illustrates how to prioritize an exposure assessment, take advantage of opportunities to conduct micro-environmental measurements, and collect personal monitoring and biological marker samples. A daily activity log is briefly described. PMID- 2258278 TI - Association of indoor air pollution and lifestyle with lung cancer in Osaka, Japan. AB - A hospital-based case-control study among non-smoking women was conducted to clarify risk factors in non-smoking females in Japan. Cases consisted of 144 non smoking female lung cancer patients, and these were compared to 713 non-smoking female controls. The odds ratio (95% confidence interval) for use of wood or straw as cooking fuels when subjects were 30 years old was estimated as 1.77 (1.08 to 2.91). For those whose household members, other than husbands, had smoked, the odds ratio was estimated as 1.50 (1.01 to 2.32). For those whose mothers had smoked, the odds ratio was estimated as 1.28 (0.71 to 2.31). Use of heating appliances did not show an elevated risk. Some points to be noted in the study of low-risk agents for lung cancer are discussed. PMID- 2258279 TI - Environmental exposures with decreased risks for lung cancer? AB - The case for a decreased risk of lung cancer after exposure to environmental agents is evaluated using toxicological and epidemiological data. Experimental evidence demonstrates that exposure to substances which produce an inflammatory response in the lung, such as bacterial endotoxins, causes an increase in the secretion of inflammatory mediators and substances with a particular effect on tumour cells such as tumour necrosis factor (TNF). Other irritant agents, such as tobacco smoke, may also induce an activation of macrophages at low levels of exposure. Epidemiological evidence from several studies suggests that people exposed to dusts containing bacterial endotoxins have a lower lung cancer incidence than those who are unexposed. There are also some data suggesting that in certain ethnic groups, females smoking a small number of cigarettes/day, might have a lower risk for lung cancer than non-smokers. These data provide support for a hypothesis that low-dose exposures to some air pollutants might result in a decreased risk of lung cancer. PMID- 2258281 TI - A community laboratory for studies on low-risk cancer agents. AB - This paper presents the concepts underlying the establishment of a community epidemiological laboratory that could serve the diverse needs of investigators worldwide who are involved in a variety of studies on low-risk lung cancer agents. The desiderata for selecting a specific geographically defined community are suggested together with a discussion of practical applications. PMID- 2258280 TI - Simulation model of lung cancer incidence related to smoking and radon daughter exposure. AB - In recent years, the residential exposure to radon daughters has become a cause for concern as a contributing factor for lung cancer. In order to evaluate the population's risk consequences of different interpretations of the results of epidemiological studies in cohorts of uranium miners, a simulation model has been formulated. In the model, a defined population is generated as a set of individuals with a distribution of characteristics and exposures as they are known to exist in the defined population. The risk for each individual of being diagnosed with lung cancer in the next year can be determined, based on whatever interpretation is being evaluated. The risk can then be translated into an annual number of cases, and suitable controls can be identified as well. Both cases and controls have their individual risk factors of radon daughter exposure and history of cigarette smoking, and it is possible to subject these cases and controls to statistical analyses appropriate to case-control studies. This analysis can be used to see to what extent the original risk equation can be retrieved, and to what extent other risk formulations can be rejected. The simulation model can be used to evaluate conclusions drawn from prior epidemiological studies, as well as for evaluations of the effectiveness of designs for proposed studies. PMID- 2258282 TI - Histopathology of lung cancer. AB - Lung cancer is a complex problem because there are a number of different histological cell types. Those commonly grouped as bronchogenic carcinoma (epidermoid carcinoma, adenocarcinoma, large cell undifferentiated carcinoma, small cell carcinoma, and adenosquamous carcinoma) account for more than 90% of the new cases and the deaths each year. The natural history of bronchogenic carcinoma suggests that many years pass while the cancer evolves from a pre cancerous change in the bronchial mucosa, to undetectable microscopic cancer, to preclinical asymptomatic cancer and finally into a full symptomatic cancer, the phase of most lung malignancies in the tissue at diagnosis. Therefore, students of the aetiology of this disease must consider what has happened to patients 5-20 years before lung cancer is diagnosed. PMID- 2258283 TI - Boundaries of perception and knowledge for risk assessment in epidemiology. AB - The intention of the paper is to introduce the concept of thresholds or boundaries of perception and knowledge in epidemiology, especially in the context of risk assessment. The notion of causal scores is introduced. A risk pictogram is proposed as a standardized way of presenting and comparing various risks. PMID- 2258284 TI - Cancer in neck nodes with unknown primary site: role of mucosal radiotherapy. AB - Sixty-nine patients with metastatic squamous cell carcinoma in neck nodes with an unknown primary lesion were treated with curative intent between October 1964 and December 1986. Sixty-five patients received radiotherapy to the neck and at least part of the mucosa of the head and neck, whereas 4 patients received treatment to the neck only. Mucosal doses were approximately 5,000 cGy-6,000 cGy at 170 cGy 180 cGy per fraction. Eight patients (12%) subsequently developed mucosal site failures, a figure that did not differ significantly from the incidence of a second metachronous head and neck cancer following definitive irradiation in a series of 393 patients with lesions of the supraglottic larynx, pharyngeal wall, pyriform sinus, or tonsillar area. This suggests that radiotherapy was highly effective in preventing the appearance of cancer at the unknown primary site from which the neck metastasis arose. Absolute and cause-specific 5-year survival rates were 48% and 66%, respectively. PMID- 2258285 TI - Postoperative radiotherapy for oral cavity cancers: impact of anatomic subsite on treatment outcome. AB - We have retrospectively reviewed the treatment results of postoperative radiotherapy (RT) for advanced oral cavity cancers. The purpose of this study was to determine the impact of anatomic subsite on the results of treatment. Between 1975 and 1985, 51 patients with squamous cell carcinoma of the oral tongue (OT = 29 patients) and floor of mouth (FOM = 22 patients) were treated with combined surgery plus RT. All had an indication(s) for RT including advanced primary disease (T3 or T4) (29 patients), close or positive margins (34 patients), and multiple positive neck nodes and/or extracapsular extension (41 patients). With a median follow-up of 6 years, the 5-year actuarial local control rate was 74% and the rate of distant metastasis (DM) was 34%. Despite the similar T stage, margin status and median RT dose, the 5-year actuarial local failure rate was 38% for OT vs. 11% for FOM (p = 0.03). Furthermore, the median survival after recurrence was 9 months for OT and 40 months for FOM (p = 0.02). At 5 years the determinate survival for both sites was (55%), and the likelihood of developing a second malignancy was 31%. The likelihood of developing DM was 50% for FOM (N0-N1 = 3 of 12, N2-N3 = 8 of 10) and 21% for OT (N0-N1 = 4 of 21, N2-N3 = 1 of 8). This study highlights significant differences between FOM and OT cancers in response to combined surgery and RT. Future strategies should be directed at the enhancement of local control for OT and better systemic therapy for those with advanced N stage FOM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258286 TI - Modified radical neck dissection in cancer of the mouth, pharynx, and larynx. AB - A retrospective analysis of 390 determinate radical neck dissections (RND) performed for cancers of the mouth, pharynx, and larynx was carried out. There were 75 patients (19%) who had a modified RND. These were separately analyzed and the outcome was compared to those who had a standard total RND. Our goal was to assess the effectiveness of modified RND in controlling disease in the neck, and to identify its impact on survival and quality of life. Overall neck recurrence rate in the entire modified RND group was 28%, 35% in the partial RND, and 25% in the comprehensive modified RND. Neck recurrence rate was no worse in the comprehensive modified RND for N0 and N1 cases, but increased significantly (as compared to the group of patients with standard RND) in the N2 and N3 cases (52% vs. 33%). Treatment of neck recurrences following modified RND was primarily by surgery, with a 48% 3-year disease-free survival. Overall survival was the same for modified RND (68%) and for standard total RND (63%). This was true for all N stages individually. The morbidity of standard total RND is discussed and the goals of modified RND are analyzed. Definitions and a standardized nomenclature for the various types of modified RND are suggested for uniformity of reporting. PMID- 2258287 TI - Innervation of the trapezius muscle: a study in patients undergoing neck dissections. AB - Twenty-four patients with surgical section of the accessory nerve and/or its cervical contribution(s) were examined from 1 to 156 months after surgery, and compared to twenty controls. Thirteen patients had a classical neck dissection; seven had the whole length of the accessory nerve preserved but not the cervical plexus contributions. Four had the upper half of the accessory nerve sectioned, but with preservation of both the lower half and its cervical contributions. Clinical and electrophysiological studies of the three portions of the trapezius suggested the existence of an undescribed motor nerve supply to the trapezius and of a motor input from the cervical plexus contributions via the accessory nerve. The former is also supported by an anatomical study. PMID- 2258288 TI - Familial occurrence of carotid body tumors. AB - Four new cases of carotid body tumors are reported, all familial, including 2 patients with bilateral tumors. The embryology, physiology, pathology, natural history, and treatment of these rare tumors are reviewed. It is recommended that all carotid body tumors be excised unless there are contraindicating medical or technical reasons. PMID- 2258289 TI - Metallic clips as a time/cost saving adjunct to head and neck surgery. AB - Metal surgical clips are commonly used in head and neck surgery today. In this study of 10 patients, 69 vessels in the neck were ligated with tantalum clips and 68 vessels were ligated with silk ties. The times for cutting and ligating each vessel were recorded and the results show a 31-second timesavings by clipping the vessel as opposed to tying. The use of metal clips on vessels is found to be both safe and effective, while reducing operative time. PMID- 2258290 TI - Anatomic study of the otic ganglion in humans. AB - The presentation in the literature of the anatomy of the human otic ganglion (OG) has not varied much over the past three quarters of a century. Precise, similar descriptions of its size, color, shape, and relation with neighboring structures are portrayed in numerous textbooks and articles. We have carried out a study of the OG in 30 infratemporal fossae of 15 cadavers. Otic ganglia resembling the classic description were found in less than 60% of the cases. In 13%, some thickening could be seen adjacent to the mandibular nerve and in 27%, no definite structure could be observed. Except for a fleeting mention of this occurrence in a textbook from 1927, substantiated by personal communication with an authority in the field, we could find no record of the possible absence of this structure in the available literature. We describe our findings and stress the apparent anatomic variability of the OG. The pertinent literature is reviewed. PMID- 2258291 TI - Mandibular chloroma demonstrated by magnetic resonance imaging. AB - A case of chloroma or granulocytic sarcoma in the mandible of a young child is presented with magnetic resonance imaging (MRI) features. PMID- 2258292 TI - Arteriovenous malformation of the maxilla. AB - The highly vascular nature of the head and neck area provides a particularly enhanced challenge to the head and neck surgeon when a vascular lesion is encountered. Vascular malformations in this area are classified according to the microanatomical architecture and clinical appearance of the lesion. Although bleeding is a common presentation with vascular malformations, other local and systemic problems may be associated with this problem. An unusual case of an arteriovenous malformation of the ethmoid and maxillary sinuses which caused persistent and recurrent epistaxis is presented. A review of the current literature concerning vascular lesions of the head and neck area is included. Adequate treatment of this lesion presently includes angiographically controlled vascular embolization followed by complete surgical excision. PMID- 2258294 TI - [Venous leg ulcer. Surgical therapy]. PMID- 2258293 TI - Carcinosarcoma of the nasal cavity and paranasal sinuses. AB - Malignant neoplasms consisting of an epithelial element and 1 or more nesenchymal components are variously termed teratocarcinosarcoma, carcinosarcoma, malignant teratoma, spindle cell carcinoma, and pseudosarcomatous squamous cell carcinoma. Carcinosarcoma, consisting of a malignant epithelial element and a single malignant mesenchymal component, is extremely rare in the sinonasal tract. We report a case of carcinosarcoma involving the nasal cavity, paranasal sinuses, and anterior cranial fossa. Rapid growth and extensive local destruction are prominent features of this tumor, emphasizing the need for early diagnosis and prompt institution of aggressive therapy. The clinical presentation, pathologic features, and clinical course are detailed. PMID- 2258295 TI - [UV exposure in the workplace. Apropos the establishing of threshold limit values]. AB - Although UV exposure is present at many workplaces, it has not gained much attention. Particularly with regard to UVA, the UV threshold limit values for acute effects used to date are insufficient, and there are no obligatory limits to prevent the sequels of chronic UV exposure. More precise threshold limit values have been published only preliminarily (DIN-Standard No. 5031, part 10). There is a need for regulations governing the supervision of occupational UV exposure and the individual protection of exposed persons. PMID- 2258296 TI - [Retinoid-induced changes of the bones and ligaments]. AB - Bone and ligament lesions induced by systemic retinoids (premature epiphyseal closure, osteophytes, calcification of ligaments, osteoporosis, etc.) are radiologically nonspecific. We assessed the incidence of "possibly retinoid induced bone and ligament lesions" (MRKBV) in 46 patients (aged 24-82 years) who had been treated with various systemic retinoids for a variety of chronic dermatoses for an average of 4.5 years and compared the data with observations in a similarly structured group of control patients. All types of MRKBV were found more frequently in the retinoid group (41.3% vs 30.2%) and were more severe. Differences were only slight, however, being statistically significant only for moderate and severe MRKBV and for calcification of ligaments. Within the retinoid group, MRKBV were strikingly correlated with age, whereas no correlation was found with duration of treatment, mean daily and cumulative retinoid dose, underlying dermatosis, type of retinoid used or presence of other retinoid side effects. Within the control group, MRKBV were also correlated with age, although to a lesser degree. We conclude that retinoids amplify and accelerate physiological and pathophysiological remodelling of the bones, thereby producing a varied range of lesions, which are characteristic for the age and the individual constitution of the patient treated. Retinoid-induced bone and ligament lesions, as a rule, do not cause subjective symptoms and are not associated with predictive or accompanying laboratory values. Also, MRKBV are not paralleled by other retinoid-induced side-effects (hyperlipidaemia, elevation of liver transaminases). In 16 cases in which bone X-ray had been performed prior to retinoid treatment, no indication of reversibility of MRKBV was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258297 TI - [Postoperative adjuvant therapy with interferon alfa-2B following laser surgery of condylomata acuminata]. AB - Sexually transmitted diseases caused by human papilloma viruses, such as condylomata acuminata, are increasing in incidence and are often difficult to treat because of their tendency to recur. Many reports in the literature document the usefulness of interferons topically or systemically in these diseases. A randomized study was conducted to evaluate interferon Alfa-2b (Intron A) as adjuvant therapy following CO2 laser surgery of condylomata acuminata. A low-dose regimen was administered (two courses with 1 million I.U. s.c. daily for 6 days with a 2-week interval between the courses) and had hardly any side-effects. The recurrence rate in the therapy group was significantly reduced (42% vs 81%), so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed. PMID- 2258298 TI - [Acute febrile neutrophilic dermatosis (Sweet syndrome). A retrospective clinical and histological analysis]. AB - Acute febrile neutrophilic dermatosis (Sweet's syndrome) was first described in 1964. The condition presents with rapidly developing inflammatory plaques, a neutrophilic dermal infiltrate, fever and leucocytosis. In this study, clinical and histological features of 18 patients with Sweet's syndrome have been analysed. The arms (83%), face (67%) and legs (67%) were the most common sites of involvement. Morphologically, plaques, nodes and pseudo-vesicles prevailed. Elevated ESR (89%), fever (72%) and peripheral blood leucocytosis (44%) were noted in many, but not all, cases. Histology revealed a dermal infiltrate with numerous neutrophils (100%) without vasculitis. Nuclear dust (72%) and extravasation of erythrocytes (44%) were also encountered. Collagen degeneration was not observed. Differential diagnosis included erythema multiforme, erythema nodosum and adverse drug reaction. Possible causative factors observed were upper respiratory tract infection, gastrointestinal infection, and malignancies. Sweet's syndrome may be considered as an extreme manifestation within a continuous spectrum of cutaneous reactions to various stimuli or as an ill defined entity that has some overlap with other dermatoses. PMID- 2258299 TI - [Epithelioid sarcoma]. AB - Epithelioid sarcoma is a rare soft tissue tumour, which was first described in 1970. The tumour occurs mostly in young adults and is characterized by multiple recurrences and late metastases. Two patients with epithelioid sarcoma are presented. Clinical and histological features and treatment are discussed. PMID- 2258300 TI - [Hutchinson-Horton ulcero-necrotizing cranial arteritis]. AB - Arteritis cranialis ulcero-necroticans Hutchinson-Horton is the necrotizing variant of giant-cell temporal arteritis, which was first described by Hutchinson in 1890 and Horton in 1932. Although the histomorphological findings (occluding proliferation of the intima, destruction of the elastica interna, giant-cell infiltration) suggest reactive pathomechanisms, the aetiology of the disease remains rather uncertain. The hypothesis currently favoured is that auto immunological processes originate from vascular alterations and subsequently lead to the recognition of antigenic determinants by the host immune system being followed by immunological response mechanisms clinically manifest as vasculitis. Arteritis cranialis is most frequently found in the temporal artery; however, the reasons for this preferential location are not clearly established, and giant cell arteritis can also be found elsewhere. Ulceration of the skin can be encountered and may affect large areas of the scalp, depending on the vascular perfusion pattern involved. The case report described in this paper comprises anamnestic data, clinical and serological findings, and the histological picture typical for giant-cell arteritis. Stress is laid on the importance of early diagnosis to prevent irreversible complications with possibly fatal outcome. PMID- 2258301 TI - [Grotton's acrogeria with bone involvement]. AB - A 13-year-old girl had a bird-like face, deficiency of the subcutaneous fatty tissue, dry, thin, transparent and wrinkled skin, especially on the hands and feet, prominent veins and telangiectasia and mottled hyper-pigmentation. X-ray studies revealed acro-osteolysis of the hands and feet. The clinical features corresponded well with Gottron-type acrogeria. The clinical symptoms of premature ageing syndromes, such as progeria, lipodystrophia totalis, Cockayne syndrome, metageria and acrogeria are summarized briefly and compared with the clinical picture observed in our patient. PMID- 2258303 TI - [Birch pollen allergy in relation with hypersensitivity for various kinds of fruit]. PMID- 2258302 TI - [L-tryptophan-induced eosinophilia-myalgia syndrome with features of diffuse fasciitis with eosinophilia]. AB - Two female patients developed localized scleroderma on the trunk and the thighs after oral ingestion of L-tryptophan for some years. Both patients reported acute progressive myalgia and weakness of the proximal parts of the extremities. On laboratory evaluation, the leucocyte count was approximately 20,000/mm3, with 38% blood eosinophils in one patient and 53% in the other. The ESR was slightly elevated; electrophoresis and muscle enzymes were normal. Skin and muscle biopsies revealed characteristic features of diffuse fasciitis with eosinophilia. High-dose glucocorticoid therapy resulted in a rapid normalization of the ESR and blood eosinophilia, whereas the scleroderma showed little improvement. The diffuse edema observed in one patient receded within a few days. A correlation between oral ingestion of L-tryptophan and the eosinophilia-myalgia syndrome has been reported recently, and the present case reports must be discussed in the light of this observation. Both patients developed a tryptophan-induced scleroderma-like illness resembling diffuse fasciitis with eosinophilia (Shulman's syndrome). PMID- 2258304 TI - [Analysis of hair for body burden of heavy metals]. PMID- 2258305 TI - Cardiovascular disease: reducing the risk through cholesterol screening. PMID- 2258306 TI - Cholesterol analyzers. AB - We evaluated eight cholesterol analyzers from eight manufacturers, basing our ratings on the accuracy of the cholesterol results (from both fingerstick and venous samples) compared with the national reference method for cholesterol; repeatability (precision) of the cholesterol results; human factors design; suitability for off-site testing; sample analysis time and throughput; and the effects of sample interferences and electrical disturbances on cholesterol test results. Although many of the units perform additional tests, we did not evaluate performance for these tests; our ratings are based solely on the cholesterol tests performed in this evaluation. We rated seven units Acceptable. We rated one unit Unacceptable because it provided inaccurate and imprecise cholesterol results; also, its reagent system has inherent problems that contribute to human error and, thus, erroneous results. The manufacturer is no longer marketing this unit but is supporting the reagents. We found advantages and disadvantages for each Acceptable unit. To help users choose the appropriate unit for specific applications, we developed a Selection Factors table based on features and applications; this table is presented in the Discussion section. We recommend that all of these units be operated by qualified personnel to minimize the potential for human error. [See "Improved Regulations for Clinical Laboratory Tests."] For further discussion of related issues, see the Clinical Perspective, "Cardiovascular Disease: Reducing the Risk through Cholesterol Screening"; "Cholesterol Readers"; and "The Discontinued Johnson & Johnson CLA 200" in this issue. PMID- 2258307 TI - PPG biomedical OR SARAcap, SARAcap PLUS, and SARAcap A.G. gas monitors. PMID- 2258308 TI - Augustine Medical Bair Hugger patient warming systems models 200 and 250. PMID- 2258309 TI - Restricted draw in Schrader-type vacuum fittings. PMID- 2258310 TI - Fading images on thermal paper. PMID- 2258311 TI - Duplex ultrasound scanners: an evolving technology. PMID- 2258312 TI - Oxygen regulator fire caused by use of two yoke washers. PMID- 2258313 TI - Freud's last will. PMID- 2258315 TI - Ontogenesis of boyhood gender identity disorder. PMID- 2258314 TI - Androgyne becomes bisexual in sexological theory: Plato to Freud and neuroscience. AB - Plato conceptualized primordial humans as androgynes, the children of the moon. The primordial hermaphroditism of the mammalian embryo became known 2 1/2 millennia later in the mid-19th century. By 1864 Ulrichs had transposed the new knowledge from embryology to sexology to explain those to whom he gave the name Urnings (after Uranus who gave womanless birth to Venus from sea spume) as having "a woman's mind trapped in a man's body" (anima muliebris corpore virili inclusa). Urning became displaced by sexual inversion, and eventually by homosexual, a term coined together with heterosexual by Kertbeny as recently as 1869. The embryological principle of primordial hermaphroditism became linked to evolutionary Darwinism by way of Haeckel's principle of recapitulation, epitomized as "ontogeny recapitulates phylogeny." The recapitulation principle became linked, in turn, to the principle of intrapsychic primordial bisexuality, which became a cornerstone of Freud's psychoanalytic theory. Genetics influences the outcome of bipotentiality not directly but by way of hormonal programming of the brain, prenatally or neonatally, rather than pubertally and in maturity. Bipotentiality within the brain has been investigated chiefly in the hypothalamus where male/female dimorphism has been recognized, but its determinants and stages of differentiation, both prenatal and postnatal, remain to be fully ascertained. Neuroanatomical research on the outcome of male/female bipotentiality as gay, straight, or in between is politically and morally opposed by those who postulate a bipotential preference or voluntary choice. In stimulus-response associationism, to which behavior-modification theory belongs, bisexuality is equipotential, and either alternative may be evoked, ostensibly, dependent on the stimulus situation. In ethological theory, the effectiveness of stimulus-response bonding is confined chronologically to a critical period of development and is restricted phylogenetically by an innate recognition mechanism and an innate releasing mechanism. These limits are compatible, however, with some degree of both individual and ethnic variation. PMID- 2258316 TI - Free association and changing models of mind. AB - The method of free association, like most major psychoanalytic concepts, was developed in and has been conceptually tied to a one-person, intrapsychic, drive psychology. Psychoanalysts who have retained the classical, drive-structure metapsychology have continued to emphasize the free association method, while those who have shifted to a relational, two-person, interactional or interpersonal point of view have often minimized or abandoned the free association method. This article explores this unfortunate dichotomy and examines the ways in which the free association method, stripped of its unnecessary tie to drive theory and reconceptualized within the context of a two-person psychology, remains a valuable clinical method. Free association, as a method, can be useful to psychoanalysts of all theoretical orientations as a reminder of Freud's most important discoveries, that is, of unconscious mental life, psychic determinism, psychic continuity, and meaning, as well as of the value and priority of careful, restrained, and disciplined listening to patients and of taking our lead from them. The method of free association, with the corresponding assumption of the analyst's evenly hovering attention, provides a fundamental context within which our personalities and theoretical biases, instead of being disruptions or impositions, become active and analyzable aspects of the analytic process. PMID- 2258317 TI - The concept of dissociation. AB - The concept of dissociation has been reviewed and redefined. It was also compared with other mental mechanisms. In the past, the process of dissociation and the content of the dissociation have often been lumped together although they are separate frames of reference. Moreover, very different psychic elements may be dissociated including memories, affects, and psychic structure. Dissociation is an important mental mechanism that plays a very significant role in people's adaptational efforts. In addition, dissociation is the underlying mechanism in a number of defense mechanisms. Repression, intellectualization, splitting, and other defense mechanisms rely upon dissociation to accomplish their specific tasks. Dissociation is thus believed to be the underlying and basic mechanism of many aspects of mental functioning. PMID- 2258318 TI - Psychological studies of Woodrow Wilson: comparing Freud-Bullitt and other psychobiographies. PMID- 2258319 TI - On internalization in group psychology: the group within. AB - A review of the relevant psychoanalytic literature suggests that internalization processes are generally depicted as occurring only within the framework of the family. By contrast, the developmental psychology literature stresses the additional importance of internalized child and adolescent group experiences. Salient recollections from professionals' and patients' group life were offered to buttress the contention that gratifying as well as stressful group experiences are subject to internalization and to subsequent externalization, especially in the context of free-associative psychotherapy. PMID- 2258320 TI - Borderline personality organization and the transition to the depressive position. PMID- 2258321 TI - Does neurology inform psychoanalysis? A case report. AB - In these days of malpractice suits it has become increasingly important that the psychoanalyst make correct diagnoses and institute appropriate treatment. The significance of this statement is enhanced by the fact that the opinion is being increasingly enunciated that there is no such disorder as conversion hysteria. Accordingly the psychoanalyst needs to keep up to date about relevant neurological matters. The present article reports a case of a young women who had been treated psychoanalytically for many years without the organic nature of her disorder being grasped. Appropriate pharmacological therapy produced prolonged remission of her symptoms. PMID- 2258322 TI - New antifungal antibiotics pradimicins FA-1 and FA-2: D-serine analogs of pradimicins A and C. AB - Pradimicin FA-1 was produced via directed biosynthesis with substitution of D serine for D-alanine in the 15-position of pradimicin A. This substitution was achieved by the addition of D-serine to the culture medium of Actinomadura hibisca P157-2. Likewise, pradimicin FA-2 was co-produced along with pradimicin FA-1 when the pradimicins A and C producing strain, A. hibisca A2493 was grown in D-serine-supplemented medium. The new pradimicin analogs share a common core structure of 5,6-dihydrobenzo[a]naphthacenequinone substituted by D-serine at C 15, but differ in the disaccharide moiety at C-5. Pradimicin FA-1 has an N methylamino sugar and D-xylose. Pradimicin FA-2 is the des-N-methyl analog of pradimicin FA-1. The in vitro and in vivo antifungal activity of the analogs was comparable to that of pradimicin A. PMID- 2258323 TI - Mycenon, a new metabolite from a Mycena species TA 87202 (basidiomycetes) as an inhibitor of isocitrate lyase. AB - Mycenon (C11H5Cl3O3), a new inhibitor of isocitrate lyase (EC 4.1.3.1) was isolated from the culture broth of a basidiomycete, Mycena sp. Mycenon is a novel chlorinated benzoquinone derivative which is also active against bacteria and fungi. Malate synthase (EC 4.1.3.2) the second key enzyme of the glyoxylate cycle was not affected by mycenon. Isocitrate lyase preparations from plants, bacteria and fungi were sensitive. The following Ki-values for mycenon have been determined: Ricinus communis, 5.2 microM; Acinetobacter calcoaceticus, 11 microM; Neurospora crassa, 7.4 microM. The structure of mycenon has been determined by a single crystal X-ray analysis. PMID- 2258324 TI - Structures of agglomerins. AB - Structures of a series of new antibiotics, agglomerins A, B, C and D, which are active against a variety of anaerobic bacteria, were determined to be 1-acyl-2,3 dihydroxy-1,3-butadiene-1-carboxylic acid, (1----3)-gamma-lactones, i.e., 2-acyl 4-ylidenetetronic acids with different hydrocarbon chains in the acyl group. Their common chromophore exhibited tautomerism in solution. The relationship of their structure to the activity against anaerobes is discussed. PMID- 2258325 TI - Antibacterial activity and chemical modifications of PS-5 at the C-3 side chain. AB - Using PS-5 as starting material, the effects of chemical modification at the C-3 side chain were studied on the antibacterial activity against Gram-positive and Gram-negative bacteria including beta-lactamase-producers. Among 35 side chains tested, 4-pyridylthio showed the highest antibacterial activity against the Gram positive bacteria, and D-cysteinyl against the Gram-negative microbes. In general, compared with acetamidoethylthio in PS-5, basic side chains showed improved antibacterial activity against the staphylococci and pseudomonads, whereas the antibiotic activity against the Gram-negative bacteria decreased with bulky side chains. The introduction of 6-aminopenicillanate and 7 aminocephalosporanate to the C-3 side chain of carbapenem significantly reduced the antibacterial activity against the beta-lactamase-producing microbes. PMID- 2258326 TI - Epimerization of erythromycin derivatives. AB - Dirithromycin (3) isomerizes upon dissolution in different solvents. From X-ray analysis of V-T 108, an analogue of dirithromycin, and comparative 1H and 13C NMR, and MS data, the isomer of dirithromycin was confirmed to be the C-16-(S) epimer. The ratio of the two epimers at equilibrium conditions was approximately 8:2 (R/S) in methanol at room temperature. PMID- 2258328 TI - R-plasmid mediated transfer of beta-lactam resistance in Bacteroides fragilis. AB - We described plasmid mediated transfer of resistance to beta-lactam antibiotics between Bacteroides fragilis strains. Ampicillin-resistance was transferred from B. fragilis strain GAI-10150 to a B. fragilis strain JC-101 with a frequency of 10(-6)/input donor by a filter mating technique. A common plasmid band, named pBFKW1, was found in both the donor and the transconjugants. The plasmid was purified by an ethidium bromide-CsCl ultracentrifugation. The molecular size of the plasmid pBFKW1 which seemed to encode the beta-lactam resistance and beta lactamase production was estimated ca. 40 kb by the analysis of endonuclease digest. Substrate profile of the enzymes derived from the donor and a transconjugant were of cephalosporinase character. PMID- 2258327 TI - Evaluation of the electrophilicity of DNA-binding pyrrolo[2,1 c][1,4]benzodiazepines by HPLC. AB - An HPLC assay is described that can be used to study the covalent bonding interaction of carbinolamine-containing pyrrolo[2,1-c][1,4]benzodiazepines with the model nucleophile thiophenol, in order to evaluate electrophilicity at the C 11-position. Preliminary experiments with anthramycin, tomaymycin and neothramycin show that their reaction with thiophenol follows second-order kinetics, but the ranking order of reactivity (neothramycin greater than tomaymycin greater than anthramycin), does not correlate with either in vitro cytotoxicity or in vivo antitumour activity. This suggests that other factors such as non-covalent DNA-interaction or drug transport play a more crucial role in biological activity than simple alkylating ability. This assay should, however, prove a useful tool in the study of structure-activity relationships for this series of compounds and provide "C-11-electrophilicity" parameters for use in Hansch analysis and related studies. PMID- 2258329 TI - Nitrilase-catalyzed production of pyrazinoic acid, an antimycobacterial agent, from cyanopyrazine by resting cells of Rhodococcus rhodochrous J1. AB - Using resting cells of Rhodococcus rhodochrous J1, in which a large amount of nitrilase is induced, a simple and efficient bioconversion process for the production of pyrazinoic acid, an antimycobacterial agent, through catalysis by a nitrilase was developed. The reaction conditions for production of pyrazinoic acid were optimized. Under optimum conditions, 3.5 M cyanopyrazine was converted to pyrazinoic acid, with a molar conversion yield of 100%. The highest yield achieved corresponded to 434 g of pyrazinoic acid per liter of reaction mixture. The synthesized pyrazinoic acid was isolated and identified physico-chemically. PMID- 2258330 TI - Microbial conversion of milbemycins: 30-oxidation of milbemycin A4 and related compounds by Amycolata autotrophica and Amycolatopsis mediterranei. AB - Microorganisms were screened for their ability to modify milbemycin A4 (1a). Many strains, mostly actinomycetes and zygomycetes, were found to convert milbemycin A4 (1a) to one or more new products. Among these products, M-1, M-2, and M-3 were obtained using Amycolata autotrophica subsp. amethystina ATCC 35204, and were identified as 30-hydroxymilbemycin A4 (1b), 26,30-dihydroxymilbemycin A4 (1c), and milbemycin A4 30-oic acid (1d), respectively. Other milbemycins and LL-F28249 alpha (7a) also underwent 30-hydroxylation by the microorganism. 22,23 Dihydroavermectin B1a (8a) was not hydroxylated at any position by A. autotrophica subsp. amethystina ATCC 35204, but a corresponding hydroxyl product at the C-30 position was obtained using Amycolatopsis mediterranei IFO 13415. PMID- 2258331 TI - A new antibiotic, 13-hydroxyglucopiericidin A. Isolation, structure elucidation and biological characteristics. PMID- 2258332 TI - Synthesis of 8-chloro-3',4',5,7-tetrahydroxyisoflavone possessing antioxidant activity. PMID- 2258333 TI - Isolation and structural elucidation of antioxidative agents, antiostatins A1 to A4 and B2 to B5. PMID- 2258334 TI - A new piericidin rhamnoside, 3'-rhamnopiericidin A1. PMID- 2258335 TI - Identification of the inhibitory activity of carbazomycins B and C against 5 lipoxygenase, a new activity for these compounds. PMID- 2258336 TI - Quinolones in perspective. AB - Fluoroquinolones have been in use for the past five years. The agents inhibit Enterobacteriaceae, Pseudomonas aeruginosa, and staphylococci, but some agents lack activity against streptococci and none of the commercially available agents inhibits anaerobic species. The fluoroquinolones possess many pharmacological advantages which have made them excellent therapy for urinary, selected respiratory, gastrointestinal, skin, soft tissue, bone, and sexually transmitted infections. They have also proved useful as prophylaxis in neutropenic patients. A major problem for the future is that inappropriate and indiscriminate use of quinolones will cause rapid development of resistance, particularly among staphylococci and P. aeruginosa. PMID- 2258337 TI - Pefloxacin in lower respiratory tract infections. AB - To determine the efficacy and safety of pefloxacin in the treatment of lower respiratory tract infections, a multicentre trial involving four departments of respiratory diseases was performed. One hundred and eight patients were admitted to the study: most of them were affected with exacerbations of chronic bronchitis or with pneumonia complicating lung cancer. Isolation and identification of responsible microorganisms from bronchial secretions was possible in 78 patients. Seven patients were withdrawn, one for worsening of the underlying disease and six for early side-effects. Thus, of 108 patients recruited, 101 completed the course of therapy (pefloxacin 400 mg bd for 5-14 days) and could be submitted to final evaluation. Of these 43 (42.6%) were cured and 48 (47.5%) showed improvement. Eradication of responsible microorganisms was achieved in 70 (90.9%) of 77 patients microbiologically evaluated. Side-effects of moderate severity were observed in 12 patients (gastrointestinal disturbances in 11 and dyspnoea in one); these did not necessitate discontinuation of therapy. PMID- 2258338 TI - Comparison of pefloxacin with ceftazidime in severe bronchopulmonary infections. AB - In a prospective open randomized multicentre trial pefloxacin (400 mg twice daily, orally) or ceftazidime (2 g twice daily iv) were given to 82 and 88 patients, respectively, with serious bronchopulmonary infection, defined as: infection occurring in high risk patients, or infection that had failed to respond to previous antimicrobials, or infection by a multiresistant pathogen. An additional nitroimidazole was allowed if the culture demonstrated the presence of anaerobes considered pathogenic. Efficacy analysis was possible in 139 patients, 70 in the ceftazidime group, 69 in the pefloxacin group. In the efficacy population, 93 bacterial strains were isolated in the pefloxacin group and 89 in the ceftazidime group. There were more Streptococcus spp. in the ceftazidime group (21) than in the pefloxacin group (14) (P = 0.06). A successful clinical response was observed in 45 patients give pefloxacin (65.2%) and 51 patients given ceftazidime (72.9%). The difference was not statistically significant. There were two relapses with pefloxacin and six with ceftazidime. In the pefloxacin group 86 pathogens (91%) and in the ceftazidime group 78 pathogens (88%) were eradicated. There were 18 and 13 adverse reactions with ceftazidime and pefloxacin, respectively. In this study, pefloxacin was as effective and as safe as ceftazidime in the treatment of severe bronchopulmonary infections. PMID- 2258339 TI - Pefloxacin versus imipenem in the therapy of nosocomial lung infections of intensive care unit patients. AB - In a prospective open randomized trial pefloxacin (400 mg, iv, 8-hourly) and imipenem (1 g, iv, 8-hourly) were given for 5-30 days to 35 and 36 ICU patients, respectively, suffering from bronchopneumonia (54) or purulent bronchitis (17). All were spiking high fevers (greater than or equal to 39 degrees C) while 25 and 26 patients in the two groups were under mechanical ventilation. Underlying predisposing disorders, mainly chronic obstructive pulmonary disease, ischaemic heart disease, neurological diseases and traumatic lung injuries, were encountered in almost all. In appropriate bronchial secretion cultures, multiresistant Acinetobacter anitratus (40), Pseudomonas aeruginosa (25), various Enterobacteriaceae (17) and Staphylococcus aureus (6) were isolated. A successful clinical response, as proved by elimination of abnormal lung x-ray findings, temperature normalization and decreases in oxygen requirements, permitting weaning from mechanical ventilation and/or removal of nasotracheal intubation, was observed in 23 patients given pefloxacin (65.7%) and 19 patients given imipenem (52.8%). The differences in clinical outcome did not reach statistical significance. During therapy pathogens persisted in 9 (25.7%) patients given pefloxacin versus 18 (50%) given imipenem (P less than 0.05), while persisters developed resistance to pefloxacin and imipenem in seven and 12 patients, respectively (P less than 0.05). Tolerance was excellent for both antimicrobials. In the therapy of lung infections in ICU patients, pefloxacin when compared to imipenem was associated with more promising results, lower numbers of persisting pathogens and a lower incidence of resistance development. PMID- 2258340 TI - Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease. AB - Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients. PMID- 2258341 TI - Single dose pefloxacin compared with multiple dose co-trimoxazole in cystitis. AB - In a double-blind multicentre study the efficacy and safety of a single-dose treatment with pefloxacin (800 mg) was compared with a five-day treatment regimen of 960 mg co-trimoxazole twice daily in the therapy of acute uncomplicated cystitis in women. In order to maintain blindness, patients in the pefloxacin group received placebo to complement the full number of tablets. Nine centres were involved; 155 patients received pefloxacin and 161 patients received co trimoxazole. Of these, 140 patients treated with pefloxacin and 145 with co trimoxazole were considered valid for efficacy and safety analysis. At the first follow-up, after seven to ten days, 97.1% of the pefloxacin group and 95.2% of the co-trimoxazole group were bacteriologically cured. At the second follow-up visit, after 28 to 42 days, the urine culture was negative in 95.0% of the pefloxacin group and 90.3% of the co-trimoxazole group. A single dose of 800 mg pefloxacin was demonstrated to be as safe and at least as effective as a five-day regimen of co-trimoxazole in the treatment of uncomplicated cystitis. PMID- 2258342 TI - Single-dose pefloxacin versus five-days treatment with norfloxacin in uncomplicated cystitis in women. AB - In a double-blind four-block randomized trial the efficacy and tolerance of a single dose of pefloxacin 800 mg was compared with a five day treatment with norfloxacin 400 mg twice daily in the treatment of uncomplicated urinary tract infections in general practice. The 222 patients included were all healthy non pregnant women, aged between 18 and 65 years, with dysuria, urinary frequency or urgency, who visited their general practitioner. Outcome parameters were the rates of resolution of symptoms after eight to ten days (T2) and after six weeks (T3), the bacteriological response at T2 and T3, and the tolerance of pefloxacin and norfloxacin. Only slight differences were demonstrated at any stage and after six weeks the success rates in the pefloxacin group were not different from those in the norfloxacin group. Tolerance in both groups was rated as satisfactory, although the higher dose of pefloxacin caused more gastrointestinal side effects. PMID- 2258343 TI - A clinical trial of pefloxacin in prostatitis. AB - Thirty-one patients with initial, recurrent or chronic prostatitis mainly caused by Enterobacteriaceae were treated with pefloxacin 400 mg bd for three to 105 days (median, 28 days). The clinical and bacteriological results four weeks after the end of the treatment, were: 23 patients (74%) cured, 21 without reinfection and two with reinfection, failure in two and relapse in six patients. Side effects, which were definitely related to pefloxacin, occurred in seven patients (22.5%) and were of a photosensitization-, muscular- and neuropsychic-type. A high eosinophil count was observed in another patient. In one patient, treatment was withdrawn because of side-effects. PMID- 2258344 TI - Prospective randomized comparison of pefloxacin and ampicillin plus gentamicin in the treatment of bacteriologically proven biliary tract infections. AB - One hundred and eighty-nine patients with acute cholecystitis or cholangitis requiring antibacterial therapy and surgery were randomly allocated in a prospective open study to receive either iv or oral pefloxacin (800 mg per day) or a combination of iv or oral ampicillin (4 g per day) and gentamicin (240 mg per day im). Ninety-two patients had to be withdrawn from the efficacy analysis, mainly because of negative baseline culture, but occasionally because of isolation of bacteria resistant to the study drugs. In the 97 evaluable patients (90 with cholecystitis and 7 with cholangitis) the clinical cure rates were excellent and similar for both groups: 49/50 (98%) for pefloxacin and 45/47 (95.7%) for the combination; the respective bacteriological success rates were 100% and 91.5%. Three patients in the pefloxacin group and six patients in the ampicillin-gentamicin group reported mild and transient side effects. PMID- 2258345 TI - Effect of pefloxacin on microorganism: host cell interaction. AB - Recent evidence indicates that certain antibiotics affect bacterial adherence and phagocyte-micro-organism interactions. These interactions are important in the early stages of bacterial pathogenesis, that is, attachment to mucosal surfaces and invasion. Among the antibiotics of interest in this field are the fluoroquinolones. Sub-MICs of pefloxacin can alter the ability of Gram-positive cocci (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative bacilli (Escherichia coli) to adhere to different eukaryotic cells (uroepithelial and buccal cells) and to fibrin-platelet matrices. The mechanism by which pefloxacin reduces adhesion is not completely understood. However in the case of Esch. coli, the inhibition of haemagglutination and adherence corresponds to: (1) a decrease in production of fimbriae; (2) changes in the composition of outer membrane proteins; and (3) an effect on partition coefficient (carried out with the PEG/dextran system) which can be attributed to changes in electric and/or hydrophobic properties of the Esch. coli surface. The first step of phagocytosis is represented by adherence of opsonized bacteria to the membrane receptors of phagocytes. Consequently, the action of pefloxacin on phagocytosis is also of importance. Pretreatment of bacteria (Staph. aureus, Ent. faecalis, Esch. coli and Legionella pneumophila) with 1/4 the MIC of pefloxacin leads to an increase in uptake of the different strains by phagocytes (polymorphonuclear leucocytes and macrophages). Exposure of the phagocytes to 10 mg/l of pefloxacin enhances phagocytosis of strains that have not been pretreated. Finally, entry of antibiotics into phagocytic cells is a prerequisite for activity against intracellular organisms. The concentration of pefloxacin by polymorphs and macrophages is high (intracellular concentration/extracellular concentration = 5 10). Such findings correlate well with the intracellular activity of pefloxacin, demonstrated with guinea pig macrophages and different bacteria (Staph. aureus, L. pneumophila). PMID- 2258346 TI - A randomized multicentre trial of pefloxacin plus metronidazole and gentamicin plus metronidazole in the treatment of severe intra-abdominal infections. Report from a Swedish Study Group. AB - In order to compare the efficacy and safety of pefloxacin plus metronidazole with those of gentamicin plus metronidazole, 271 patients with severe intraabdominal infection were enrolled in an open, randomized comparative trial. Seventy males and 66 females (mean age 54 years; range 18-90) were enrolled in the pefloxacin/metronidazole group and 74 males and 61 females (mean age 52 years; range 18-90) in the gentamicin/metronidazole group. After verification of the intra-abdominal infection by laparotomy, drainage or puncture and microbiological cultures, patients received iv either pefloxacin 400 mg, bd, after an 800-mg loading dose, or gentamicin 1.4 mg/kg body weight every 8-24 h depending on the renal function. Metronidazole was given to both groups as a 500 mg intravenous infusion tid. Eighty-seven patients were excluded from the efficacy analysis, principally because of unproven infection, previous antimicrobial therapy or treatment duration less than three days. Ninety-four of 104 patients receiving pefloxacin/metronidazole (90.4%) were cured or improved and there were two failures and eight relapses. In the gentamicin/metronidazole group, 64 of 80 patients (80.0%) were cured or improved while there were three failures, nine relapses, and two deaths. The bacteria originally isolated were eradicated in similar proportions of the patients in the two groups. Eleven of 136 patients receiving pefloxacin/metronidazole (8.1%) and seven of 135 patients given gentamicin/metronidazole (5.2%) had adverse reactions. This study shows that pefloxacin can be considered as effective and safe as gentamicin for the treatment of severe intraabdominal infections. PMID- 2258347 TI - The efficacy and safety of pefloxacin in the treatment of typhoid fever in Algeria. AB - The efficacy and safety of pefloxacin 400 mg twice daily for seven days in the treatment of typhoid fever was investigated in an open, non-comparative study involving 37 patients infected with Salmonella typhi. Between day 5 and the end of treatment, all patients showed clinical improvement. The clinical cure rate at the end of the treatment period was 89.2%. One month after the end of treatment, the final assessment showed a clinical cure rate of 94.6% with relapses occurring in only two patients. Both these patients belonged to the group with negative blood cultures but positive serodiagnostic tests. Bacteriological tests confirmed eradication of the pathogen in 94.6% of patients and the relapses in the two serologically positive patients. Temperature became normal in a mean of 5.14 days. Clinical adverse reactions were reported in 5.9% (3/51) of patients (vomiting in two, transient pruritic rash in one). The results of this study indicate that a seven-day course of pefloxacin 400 mg twice daily provides a suitable alternative in the treatment of typhoid fever. PMID- 2258348 TI - Pefloxacin efficacy in gram-negative bacillary meningitis. AB - Sixteen patients with acute meningitis caused by Gram-negative bacteria were treated with pefloxacin intravenously. The age range of the patient group was six months to 85 years with a mean age of 40 years; three patients were children. In all but two patients meningitis was a complication of neurosurgical operations and fourteen of the sixteen had received prior therapy which was not successful. The causative organisms were: Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (4), Klebsiella pneumoniae (3), Enterobacter cloacae (2), Citrobacter diversus (1) and Salmonella group C (1). Pefloxacin was administered intravenously 800 mg twice a day to the adult patients (mean dosage of 21( +/- 6.7) mg/kg body weight) for a mean period ( +/- S.D.) of 11( +/- 4) days. The mean cerebrospinal fluid concentration of pefloxacin was 8.8( +/- 5.0) mg/l which was 54% of the mean peak serum concentration (16.3( +/- 8.8]. The mean MIC and MBC of the causative organisms were 1.1( +/- 1.2) mg/l and 1.64( +/- 1.2) mg/l. Thirteen patients (87%) were cured or clinically improved and twelve (80%) were bacteriologically cured. One patient failed, another patient had reinfection and one was not assessable. No side effects were observed. In the present study pefloxacin offered an efficacious and safe treatment of Gram-negative meningitis following failure of other antibiotic therapy. PMID- 2258350 TI - Pefloxacin in the treatment of bone infections associated with foreign material. AB - Thirteen patients with bone infection caused by Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens or Escherichia coli in association with implanted foreign material were treated with pefloxacin 400 mg 12-hourly for up to six months. Satisfactory results, with fistula closure and eradication of the infecting bacteria, were achieved in nine patients, who have been followed up for four to seven years. Treatment failed in two patients, with re-isolation of the infecting bacteria (P. aeruginosa; Ser. marcescens) which showed reduced sensitivity to pefloxacin. Primary failure (failure to close of the fistula and re-isolation of bacteria sensitive to pefloxacin) occurred in one patient, who achieved a satisfactory result later after removal of foreign material. Relapse after treatment occurred in one patient. Eight patients suffered migrating arthralgia (without signs of arthritis) but this did not interfere with the treatment, which was generally well tolerated. PMID- 2258349 TI - Pefloxacin versus ceftazidime in therapy of soft tissue infections in compromised patients. AB - Soft tissue infections in compromised patients are frequently caused by Gram negative organisms and particularly by Pseudomonas aeruginosa. These pathogens are effectively eradicated by pefloxacin as well as by ceftazidime. The effectiveness and safety of these two agents were compared in a prospective randomized study in 67 patients with soft tissue infections. Underlying conditions included malignant diseases, diabetes mellitus and chronic renal failure. The infections included: post operative infection, septic foot, soft tissue abscess and cellulitis. Thirty-three patients were treated with intravenous ceftazidime for a mean duration of ten days. More than half the 34 patients given pefloxacin were treated only orally for a mean period of 13 days. The clinical and bacteriological outcomes were similar in both groups. There was clinical cure or improvement in 26 pefloxacin cases and in 23 ceftazidime cases, failure in six pefloxacin cases and in seven ceftazidime and relapse in two pefloxacin and in three ceftazidime patients. The bacteriological responses were eradication in 23 pefloxacin cases and in 22 ceftazidime cases, persistence in five pefloxacin cases and in six ceftazidime cases, relapse in one pefloxacin case and in none of the ceftazidime group, reinfection in four pefloxacin cases and in three ceftazidime cases and there was one unassessed patient in the pefloxacin group and two in the ceftazidime group. Nausea and vomiting occurred in three patients and elevation of liver enzymes in another patient; all side effects were observed only in the pefloxacin treated patients. These results suggest that oral pefloxacin could offer an alternative to intravenous ceftazidime in half the compromised patients with tissue infections. However, adverse reactions due to pefloxacin administration should be watched for during such therapy. PMID- 2258351 TI - Pefloxacin: safety in man. AB - Pefloxacin has been in clinical use in France since 1985. During this period of time, the Rhone-Poulenc Drug Safety Department has received 213 spontaneous reports concerning patients who experienced a total of 316 adverse events. The level of such spontaneous reporting from physicians depends upon the frequency and the clinical significance of the events. Skin, musculoskeletal and CNS problems were the events most frequently reported. Thrombocytopenia was the most frequently reported laboratory abnormality, use of heparin being associated with this in many cases. From these data, pefloxacin in routine clinical use appears to be well tolerated. For the agent to be used in children in the future, its safety in this population should first be carefully investigated. At present it is contraindicated in children under 15 years of age. PMID- 2258352 TI - Cellular uptake, localization and activity of fluoroquinolones in uninfected and infected macrophages. AB - Pefloxacin, like other fluoroquinolones, accumulates in macrophages and several other types of nucleated cells (but not in erythrocytes). Upon fractionation of macrophage homogenates by isopycnic centrifugation in sucrose gradients, fluoroquinolones are not found associated with any specific cellular structure. We have compared the activities of pefloxacin and roxithromycin against intracellular Staphylococcus aureus in mouse J774 macrophages. Pefloxacin was significantly more active for equivalent intracellular drug concentrations (i.e. expressed by reference to the respective MICs of the drugs as determined in broth), suggesting differences in intracellular availability and/or capacity of the drugs to express their activity in the intracellular environment. The difference was enhanced by incubating the cells in acidic medium. We have also examined the cellular pharmacokinetics and intracellular distribution of pefloxacin in uninfected and Legionella pneumophila infected guinea pig macrophages. In contrast to uninfected cells from which pefloxacin was quickly released, macrophages infected with legionella retained approximately 20-30% of the accumulated pefloxacin after a 60-min wash-out. Cell fractionation studies indicated that the drug remaining in cells was associated with components of high buoyant density. These fractions also contained [3H] if cells had been incubated with [3H] labelled legionella (by in-vitro exposure to [3H]-thymidine, before phagocytosis). These results suggest that part of the intracellular pefloxacin becomes associated with legionella, or with legionella-containing cytoplasmic structures. PMID- 2258353 TI - Pharmacokinetics of fluoroquinolones in hepatic failure. AB - In patients with alcoholic cirrhosis, the pharmacokinetics of the fluoroquinolones were variously altered. The kinetics of ciprofloxacin were slightly modified in patients with mild or moderate impairment. Ofloxacin kinetics were influenced by renal dysfunction encountered in patients with ascites. Pefloxacin kinetics were markedly modified with wide variations in elimination among patients. Ascitic penetration of ofloxacin and pefloxacin was excellent. Since no relationship between ofloxacin or pefloxacin kinetics and the usual liver function tests was found, recommended dosage regimens in cirrhotic patients have to be controlled by monitoring plasma drug levels during treatment. PMID- 2258354 TI - Prevention of infections in neutropenic patients with pefloxacin. AB - Bacterial infections remain a major source of morbidity and mortality in neutropenic patients. Therefore, optimal methods of prevention seem mandatory and various means have been tested, in particular specific modalities such as chemoprophylaxis, which remains controversial. Overall, non-absorbable antibiotics have been disappointing and are less commonly used because of the poor compliance of most patients. Co-trimoxazole has been shown to be effective under certain circumstances but the emergence of resistance, and the risk of prolonging the duration of neutropenia are major drawbacks despite the advantages of co-trimoxazole being well tolerated and effective in preventing Pneumocystis carinii infections. Recently, fluoroquinolones have been developed and numerous studies of prophylaxis have been performed with norfloxacin, enoxacin, ciprofloxacin, and other agents from this class, including pefloxacin. These data show a significant reduction of bacteraemia caused by Gram-negative bacilli in neutropenic patients but a high incidence of infection caused by Gram-positive cocci, mainly streptococci. The sources of those infections are many including mucositis due to chemotherapy and/or total body irradiation, as well as changes in the patient's flora due to more effective cover against Gram-negative bacilli. Future studies should further investigate regimens to achieve optimal prophylaxis for infections caused by either Gram-negative or Gram-positive pathogens during neutropenia. PMID- 2258355 TI - Double-blind comparison of pefloxacin and cefazolin as prophylaxis in elective cardiovascular surgery. AB - A total of 162 patients (134 males and 28 females) scheduled for coronary artery bypass grafting (144) or valve surgery (18) were randomly assigned to receive, under double-blind conditions, either pefloxacin 400 mg iv or cefazolin 1.0 g 30 min before the surgical incision and then post-operatively 12-hourly x 4 or 6 hourly x 8, respectively. Positive per- and post-operative cultures were seen in 27 patients (11 pefloxacin, 16 cefazolin) and 47 micro-organisms were isolated: 34 per-operatively (21 pefloxacin, 13 cefazolin) and 13 post-operatively (4 pefloxacin, 9 cefazolin). There were five failures of prophylaxis (2 pefloxacin, 3 cefazolin): two early (less than 5 days: 1 pefloxacin, 1 cefazolin) and three late (greater than or equal to 5 days, 1 pefloxacin, 2 cefazolin) divided into (i) one major primary failure in the cefazolin group (1 cefazolin resistant Staphylococcus epidermidis mediastinitis); (ii) two minor primary failures, one in each group (Gram-positive sternal incision abscesses) and (iii) two secondary failures (1 cefazolin resistant Enterobacter cloacae and Pseudomonas aeruginosa UTI in the cefazolin group and one culture negative pneumonia in the pefloxacin group). Tolerance to both antibiotics was excellent. In our sample of patients, the efficacy and safety of pefloxacin was not different from those of cefazolin in prophylaxis in cardiovascular surgery. PMID- 2258356 TI - Pefloxacin therapy for nosocomial infections in the intensive care unit. AB - Nosocomial infections occurring in an intensive care unit (ICU) are commonly caused by aerobic Gram-negative bacilli or Staphylococcus aureus, which are frequently multi-resistant and difficult to treat and contribute significantly to the patients' morbidity in the ICU. Pefloxacin, with its wide range of antimicrobial activity, lack of serious side-effects and advantageous kinetics, is a useful drug for use in this group of critically ill patients. Pefloxacin has achieved a greater than 70% clinical cure rate and a microbiological response of over 80% in cases of nosocomial pneumonia in the ICU. Failure and superinfection has occurred with the development of resistance, particularly in Pseudomonas aeruginosa in a small number of cases, but this can be prevented by combination antimicrobial therapy. Serious side-effects, including confusion, psychiatric disturbance and other neurological abnormalities were rare and resolved on withdrawal of the drug. Drug interactions occur with cimetidine and theophylline but are usually not clinically relevant; significant interaction with warfarin occurs and the dose of warfarin needs careful adjustment. Pefloxacin is a valuable drug for use in bacteriologically proven sensitive infections and combination with aminoglycosides or beta-lactam agents should prevent the development of resistance. PMID- 2258357 TI - Monotherapy with pefloxacin in multidrug-resistant nosocomial gram-negative bacteraemia. AB - Twenty patients who developed nosocomial Gram-negative bacteraemias in the medical or surgical intensive care units were treated with pefloxacin. All organisms were susceptible to pefloxacin and had not responded to previous antimicrobial therapy. The bacteraemias were eradicated in 16 of the 20 patients, all of whom tolerated the therapy without adverse effects. PMID- 2258359 TI - Red cell enzyme defects. AB - Erythrocytes are a readily available cell type that has proved to be extraordinarily useful in the diagnosis of enzyme abnormalities, both of genetic and nutritional origin. The metabolism of red cells is reviewed briefly, particularly with respect to the consequences of abnormalities in different types of enzymes. Erythrocyte enzyme abnormalities are classified into three broad, somewhat overlapping groups: (1) those that lead to abnormalities of red cell functions; (2) those that are reflected in the red cells but whose clinical consequences are primarily manifested in other tissues; and (3) those that have no known clinical consequences. Genetic variability of red cell enzymes is discussed, and advances in understanding red cell enzyme defects at the DNA level are highlighted. PMID- 2258358 TI - Pefloxacin in the treatment of septicaemia: three years' experience. AB - Sixty cases of septicaemia treated with pefloxacin, alone (30) or in combination with other antibiotics (30) were analysed retrospectively. A satisfactory outcome was achieved in 33 (87%) of 38 evaluable Gram-negative septicaemias (including success in 25 of 29 treated with pefloxacin alone) and in 15 of 21 staphylococcal septicaemias, mainly treated with combinations of antibiotics. Failures and relapses were associated with a variety of local or systemic underlying conditions. PMID- 2258360 TI - Combined utility of gene rearrangement analysis and flow cytometry in the diagnosis of lymphoproliferative disease in the bone marrow. AB - The diagnosis of lymphoma involving bone marrow is often complicated by the presence of nonspecific lymphoid aggregates. Morphologic criteria may not permit the distinction of benign from malignant lymphoid aggregates with certainty in all cases. We combined morphology with immunophenotypic and immunogenotypic analyses of aspirated marrow cells to develop more reliable criteria for the diagnosis of marrow involvement by lymphoma. The presence of morphologically recognizable lymphoma cells in the bone marrow aspirate was always confirmed by immunogenotypic analysis. The yield of either immunophenotypic or immunogenotypic analyses on morphologically negative marrows was very low. Focal paratrabecular involvement by lymphoma was not always confirmed by immunophenotypic or immunogenotypic analyses, probably due to sampling error and factors interfering with aspiration of the lymphoid aggregates. Thus, the immunologic and molecular studies supported, but did not substantially improve upon the morphologic criteria that are in common usage for distinguishing benign from malignant lymphoid aggregates in the bone marrow. Finally, evidence of B-lymphocyte clonality was obtained in four of five cases in which there were nonspecific lymphoid aggregates in the bone marrow in the absence of otherwise clinically definable malignancy. PMID- 2258362 TI - A novel HIV vaccine strategy. PMID- 2258361 TI - Hypereosinophilic syndrome with evolution to myeloproliferative disorder: temporal relationship to loss of Y chromosome and c-N-ras activation. AB - A case of hypereosinophilic syndrome is presented in which the patient was serially observed for 4 years. Transformation to a disorder resembling chronic myeloid leukemic (CML) occurred 36 months after diagnosis; at 42 months, blastic transformation and marrow failure ensued, leading to death. Marrow examination for histopathologic, cytogenetic, and molecular biologic analyses were performed during the eosinophilic, myeloproliferative, and blastic stages. These demonstrated ras activation by virtue of a codon 12 G to C transversion mutation, predicting for substitution of glycine by alanine; in addition, we observed Y chromosome loss late in the natural history of this illness, suggesting that these genetic lesions can play a role in the profound loss of myeloid differentiation characteristic of the accelerated phase commonly observed in myeloproliferative syndromes. PMID- 2258364 TI - Labetalol in the control of cardiovascular responses to electroconvulsive therapy in high-risk depressed medical patients. AB - Labetalol, a drug with alpha- and beta-adrenergic receptor blocking effects, was used to attenuate hypertension and tachycardia associated with electroconvulsive therapy (ECT) in a series of 11 elderly patients with refractory depression and cardiovascular disease in a placebo-controlled, double-blind crossover study design. As compared with placebo, labetalol was found to blunt mean arterial pressure (MAP) increase by up to 8.26% (p less than .001), heart rate increased by up to 26.07% (p less than .001), frequency of atrial arrhythmias by up to 100% (p less than .01), and premature ventricular contractions by 41.97%. No untoward side effects were observed, and no effect on treatment outcome was noted. Labetalol appears to be an effective and safe agent to use in decreasing hypertension, tachycardia, and possibly arrhythmias in high-risk medical patients with cardiovascular disease undergoing ECT. PMID- 2258363 TI - Depression in the context of human immunodeficiency virus infection: implications for treatment. AB - A chart review of 90 male outpatients was conducted to document the type of depressive symptomatology associated with HIV infection and to review the nature of antidepressant treatment provided in two university-affiliated outpatient settings. Forty-five individuals who tested positive for HIV infection and who were treated with antidepressant medications were compared with a like number of individuals who had no known risk factors as determined by chart review for HIV infection. Although depressive symptoms were generally similar among the two groups, HIV-positive individuals reported greater decreases in sleep and appetite than the HIV-negative comparison group. Overall, imipramine and fluoxetine earned the most favorable efficacy ratings while producing minimal side effect ratings in both HIV-positive and HIV-negative patients. Among the HIV-positive patients, the asymptomatic group had a better response to treatment with antidepressant medications than either the ARC or AIDS patient groups. PMID- 2258365 TI - Patients with frequent sleep panic: clinical findings and response to medication treatment. AB - The authors present 12 cases of panic disorder patients whose sleep panic attacks represented their primary complaint at the time of admission. The patients averaged 18 sleep panic attacks per month before admission. Seven patients were treated with tricyclic antidepressants and demonstrated marked global clinical improvement and a reduction in the frequency of sleep panic attacks. The clinical and theoretical implications of these preliminary findings are discussed within the context of current theories regarding the spontaneous nature of panic attacks. PMID- 2258366 TI - The pharmacotherapy of moral or religious scrupulosity. AB - Moral or religious scrupulosity is a disabling condition which is sometimes seen in patients with obsessive compulsive disorder (OCD). The authors described 10 patients with moral or religious scrupulosity who were treated with fluoxetine or clomipramine. Seven of the 10 patients completed open treatment of at least 8 weeks without requiring adjunctive medication; 5 of those 7 patients were rated as much improved. Among the 3 patients who required adjunctive medication, 1 was rated as much improved. Of the 4 nonresponders at 3 months, 2 responded after longer treatment trials. These results suggest that extreme moral or religious concerns and behaviors might be a form of OCD and that the scrupulosity can be effectively treated with serotonin reuptake blockers. PMID- 2258367 TI - Shared features of neuroleptic malignant syndrome and alcohol abuse complications. PMID- 2258368 TI - Carbamazepine in behaviorally disturbed primary dementia patients. PMID- 2258369 TI - Fluoxetine-induced mania. PMID- 2258370 TI - Valproate in the treatment of temper outbursts. PMID- 2258371 TI - Longitudinal course of panic disorder: findings from the Massachusetts General Hospital Naturalistic Study. AB - Clinical experience and controlled studies confirm the efficacy of pharmacologic and cognitive-behavioral interventions for the acute treatment of panic disorder and agoraphobia. However, while some patients experience long periods of true remission, panic disorder remains chronic for many, with intermittent periods of acute exacerbation and continued residual distress. Findings from the Massachusetts General Hospital Naturalistic Study of the Longitudinal Course of Panic Disorder suggest that (1) a number of factors contribute to the severity and persistence of panic disorder, including phobic subtype, comorbid anxiety disorders, depression, personality disorders, and anxiety sensitivity; (2) chronicity is common; (3) for some, an anxiety diathesis is manifested early in childhood and sets the tone for later chronicity and comorbidity; (4) maladaptive personality characteristics may be manifestations of an underlying anxiety disorder; (5) patients with continued symptomatology despite improvement may benefit from the flexible integration of pharmacologic and cognitive-behavioral treatment approaches; and (6) long-term treatment is indicated for many patients. PMID- 2258372 TI - Long-term outcome for patients with panic disorder treated with cognitive behavioral therapy. AB - Psychological approaches to panic disorder with agoraphobia have concentrated on agoraphobic avoidance behavior associated with panic attacks through use of exposure-based methods. These have proven reasonably successful but few patients are "cured," and a number continue to experience anxiety and panic. More recently, treatments with the goal of reducing panic attacks directly have been developed. These are based on a new psychobiological model of panic disorder that suggests some people are predisposed to panic, particularly when under stress. A minority develop anxiety about the possibility of another panic attack and become sensitive to sensations that signal an attack. The treatment developed at our center emphasizes systematic exposure to the somatic events associated with panic, breathing training, correcting misinformation about attacks, and the catastrophic cognitions associated with panic. Both initial and long-term outcome of early studies of this treatment are presented. PMID- 2258374 TI - Panic disorder: diathesis and treatment issues. 143rd annual meeting of the American Psychiatric Association, New York, N.Y., May 12-17, 1990. Proceedings. PMID- 2258373 TI - Maintenance treatment with antidepressants in panic disorder. AB - Because panic disorder is a chronic illness, patients may require long-term pharmacologic treatment. Unfortunately, the benefits and risks of such therapy have received little study. At least two classes of antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, are effective for the treatment of panic disorder, but because relapse is common when these drugs are discontinued, many patients require maintenance treatment. However, such long term use of tricyclic antidepressants and monoamine oxidase inhibitors exposes patients to risks that include potentially fatal overdoses and hypertensive crises. Patients should be aware of the risks involved and should weigh them against the benefits of long-term use. They should reduce the dose to the lowest effective level, from time to time gradually taper medications to assess continuing need, and avail themselves of other therapies rather than rely solely on drug treatment. Above all, more research should be done on the long-term risks and benefits of antidepressant drugs. PMID- 2258375 TI - Continuation treatment of panic disorder with high-potency benzodiazepines. AB - High-potency benzodiazepines such as clonazepam and alprazolam are effective and safe in the short-term treatment of panic disorder, but less is known about their effectiveness and safety over the long term. Further understanding of these issues is important since panic disorder is usually chronic and may call for long term treatment. Available naturalistic data suggest that tolerance to the antipanic or antiphobic effects of clonazepam and alprazolam does not occur in panic disorder/agoraphobia; doses also tend to decrease over time. Withdrawal symptoms occur after short-term treatment with alprazolam, but less is known about clonazepam in this respect. Other issues discussed include management of withdrawal, clinical use of benzodiazepines, importance of comorbidity, and the use of benzodiazepines in association with behavior therapy. PMID- 2258376 TI - Thinking about stopping treatment for panic disorder. AB - The lifelong nature of panic disorder and the development of effective new treatments have focused attention on long-term use of antipanic medications, particularly benzodiazepines and their possibly addictive nature. Benzodiazepines are generally safe and effective. An understanding of the distinction between chemical dependence and physical dependence places problems involved in the use and discontinuation of benzodiazepines into perspective. Patients with a dual diagnosis of panic disorder and chemical dependence are at risk of addiction. Others may develop physical dependence but are able to discontinue benzodiazepine treatment when panic symptoms subside. The approach to benzodiazepine use and discontinuation should be different for patients with chemical dependence as opposed to patients with physical dependence. A four-step approach to discontinuation that is applicable to both groups is offered. PMID- 2258377 TI - Noradrenergic function in panic disorder. AB - There is neuroanatomical, neurochemical, neurophysiologic, and behavioral preclinical evidence that suggests that the development of anxiety or fear relates, in part, to increased brain noradrenergic neuronal activity. In laboratory animals, uncontrollable stress has been shown to be associated with increases and altered regulation of brain noradrenergic function. Pharmacologic or electrical activation of noradrenergic neurons of the major brain noradrenergic nucleus, the locus ceruleus (LC), has anxiogenic effects in nonhuman primates. Elevated LC neuron firing is associated with anxiety or fear responses in freely moving cats. These observations are supported by clinical investigations that have demonstrated abnormal noradrenergic system regulation in panic disorder patients. From a neurodevelopmental perspective, these findings may be related to the natural course of panic disorder. PMID- 2258378 TI - Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline controlled, multicenter comparison study in outpatients with major depression. AB - A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo. PMID- 2258379 TI - Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. AB - Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258381 TI - The electrocardiogram as a tool for therapeutic monitoring: a critical analysis. AB - The authors review the scientific value of electrocardiographic studies and discuss the limitations that arise from variability in technology and in standards of recording and interpretation. A consistent recording procedure and objective assessment using standardized diagnostic criteria are required, particularly in multicenter studies. Tricyclic antidepressants depress cardiac conduction at therapeutic concentrations; therefore a comparison with the electrocardiographic profile of sertraline, a specific serotonin reuptake inhibitor with antidepressant activity, was made. In four studies, sertraline was compared with placebo, with amitriptyline or placebo, and with amitriptyline alone. There were decreases in RR interval and increases in PR, QRS, and QTC intervals with amitriptyline but no effect with sertraline. Thus, sertraline had no demonstrable effects on intraventricular conduction or electrocardiographic time intervals. PMID- 2258380 TI - The effects of sertraline on psychomotor performance in elderly volunteers. AB - The psychopharmacologic effects of sertraline, a new antidepressant drug, are reviewed. A double-blind, placebo-controlled crossover study was conducted, investigating the effects of 9 days' administration of sertraline and mianserin on cognitive and psychomotor performance of elderly volunteers. The two antidepressants were given on a rising dose schedule for the first five days of treatment (sertraline 100 mg Day 1 and 2, 150 mg Days 3 and 4, and 200 mg Day 5; mianserin 10 mg Days 1 and 2, 20 mg Days 3 and 4, and 30 mg Day 5) with the highest dose (mianserin 30 mg and sertraline 200 mg) being intended for the rest of the study. To assess the effect of concomitant alcohol administration, alcohol (0.5 g/kg body weight) was given 6 hours after the last dose of each treatment. There was a severe intolerance to the effects of mianserin in this group of patients even at the lowest dose and, as many subjects were withdrawn, there was no formal analysis because of the missing data. However, the available evidence showed the expected sedative effects on a number of psychometric tests. Single or multiple doses of sertraline did not affect objective measures of performance. The addition of alcohol did not affect these results. The results indicate that sertraline has a neutral psychomotor profile in the elderly and appears to have no additive depressant effects when taken with moderate amounts of alcohol. PMID- 2258382 TI - Neurofilament proteins are co-expressed with desmin in heart conduction system myocytes. AB - We have recently shown that specialized myocytes of the rabbit heart express a cytoskeletal protein similar to the M subunit of neurofilaments (NF). Since this result was obtained using a single anti-NF-M monoclonal antibody, we tested on conduction myocytes a panel of five anti-NF antibodies, specific for each of the three NF subunits and for phosphorylated and non-phosphorylated epitopes. Two antibodies, one specific for the L subunit and one for phosphorylated M subunit of NF, reacted with specialized myocytes in immunohistochemistry. In immunoblots on conduction tissue homogenates the two antibodies recognized two polypeptides with electrophoretic mobility and solubility properties identical to those of NF L and NF-M in the sciatic nerve. The subcellular distribution of NF immunoreactivity in specialized myocytes was very similar to desmin localization; namely, it was distributed on large filamentous bundles and on fine filaments localized transversely at the level of the Z line. At the ultrastructural level, immunoreactive filaments were localized in the intermyofibrillar space and connected myofibrils with mitochondria. Co-expression of NF proteins and desmin was also observed in vitro in a minor population of cardiac myocytes cultured from embryonic rabbit heart. In most cases NF immunoreactivity co-localized with desmin, especially where filaments were well organized, but in some cells anti-NF and anti-desmin antibodies labelled different filamentous structures. These results indicate that NF proteins are structural components of the cytoskeleton of specialized myocytes and show a subcellular distribution very similar to desmin. Such a composition of intermediate filaments indicates that in these cardiac cells muscle differentiation is compatible with the expression of neuronal proteins. PMID- 2258383 TI - Effect of temperature on the assembly of tight junctions and on the mobility of lipids in membranes of HT29 cells. AB - In the human colon adenocarcinoma cell line HT29, tight junctions can be induced by treatment with appropriate proteases or salt solutions. The temperature dependence of induced tight junction formation is characterized by a marked sigmoidal behavior. The different methods of induction used in this study were characterized by threshold temperatures ranging from 15 to 32 degrees C. Fluorescence photobleaching recovery measurements of the lateral diffusion of a fluorescent phospholipid probe in the cellular plasma membrane gave no evidence for a phase transition or for alteration in the organization of membrane lipids in lateral domains in the temperature range between 0 and 37 degrees C. Moreover, dynamic parameters of the probe in the plasma membrane did not change substantially on mild treatment with trypsin. Thus, the temperature dependence of tight junction formation is not dictated by the bulk properties of the cytoplasmic membrane lipids. The observed temperature dependence suggests that the assembly of tight junctions is a cooperative process, which may involve conformational rearrangement in a protein precursor subsequent to its proteolytic activation. PMID- 2258384 TI - Adsorptive endocytosis and membrane recycling by cultured primary bovine brain microvessel endothelial cell monolayers. AB - The dynamics of membrane recycling were examined in primary cultures of brain microvessel endothelial cells (BMECs). Because the BMEC surface was dominated by galactosylated glycoconjugates, ricin agglutinin (RCAI) was used as a tracer to follow the endocytosis and recycling of RCAI binding sites. These binding sites accounted for 75% of the iodinatable or most externally disposed plasma membrane proteins. Because greater than 90% of the RCAI that had bound to BMECs was removed by a brief, nontoxic treatment with galactose, the amounts and kinetics for internalization and efflux of [125I]RCAI were measured. Both endocytosis and efflux were energy dependent. By using pseudo-first-order kinetics, the t1/2 values for RCAI binding, internalization and efflux were 5, 18 and 13-14 min, respectively. By comparing efflux with and without galactose present, we found that 60% of the RCAI binding sites that had been internalized were returned to the cell surface and reinternalized. Quantifying the distribution of gold-RCAI following internalization showed kinetics consistent with that obtained using radiolabeled RCAI. Both horseradish peroxidase (HRP) and gold-conjugated RCAI that had bound BMEC at 4 degrees C became localized within more caveolae within 2.5 min of warming to 37 degrees C to permit endocytosis. With time, RCAI appeared within endosomes and tubules and vesicles of which some were located in the trans-Golgi network (TGN). The distribution of HRP-RCAI contrasted with that of free HRP, which was not routed to the TGN. The absence of RCAI conjugates in association with the basolateral membrane domain suggested the presence of functional tight junctions and maintenance of polarity throughout the duration of these experiments. These results showed that membrane recycling was more extensive and much slower than fluid-phase endocytosis in cultured BMECs. Moreover, we found that endocytosis of membrane by BMECs in culture was similar to that reported for brain endothelium in vivo in that a fraction of the cell surface membrane was routed to the TGN. PMID- 2258385 TI - An endogenous carbohydrate-binding protein of baby hamster kidney (BHK21 C13) cells. Temporal changes in cellular expression in the developing kidney. AB - Asialofetuin (ASF) coupled to Sepharose has been used to isolate a Mr 30,000 protein from Triton X-100 extracts of the baby hamster kidney cell line BHK21 C13. Binding to ASF-Sepharose was specific for terminal beta-galactosyl residues. The lectin requires detergent for optimal solubilization and binding is independent of Ca2+ or reducing reagents. The lectin was labelled in a lactoperoxidase-catalysed iodination of intact BHK21 C13 cells, suggesting that it is associated with the cell surface. Antibodies to the lectin identify in Western blotting cross-reactive components in established cell lines of kidney (MDCK, NRK) and non-kidney (L, CHO, 3T3) origin. In young adult hamsters, the lectin is expressed in colon and duodenum and in lesser amounts in ileum, stomach, lung, liver and testes but is absent in kidney. The lectin is expressed in late embryonic and newborn hamster kidney but expression declines during 14 days after birth. Immunofluorescent staining of cryostat sections of newborn hamster kidney and intestine show that the lectin is expressed at apical epithelial surfaces. The presence of the lectin at the luminal surface of kidney tubules suggests a tubular origin for the BHK21 C13 cell line. Possible functions of the Mr 30,000 lectin in kidney development are discussed. PMID- 2258386 TI - Monensin does not consistently inhibit the spreading of normal or Duchenne fibroblasts on glass. AB - The spreading on glass of monensin-treated normal and Duchenne fibroblasts has been investigated with the intention of extending this approach to a study of the comparative spreading of these cells on differing substrata. Untreated normal and Duchenne fibroblasts varied considerably in their ability to spread on glass. The spreading properties of normal and DMD fibroblasts treated in four different ways were compared: (1) pre-incubated and plated without monensin; (2) pre-incubated with, but plated without monensin; (3) pre-incubated without, but plated with monensin; (4) pre-incubated and plated with monensin. The response to plating with monensin (and pre-incubation/plating with monensin) also varied from patient to patient, but no statistically significant differences in the degree of spreading between the four treatment groups were observed in pooled data for either normal or dystrophic fibroblasts. Our data thus do not substantiate the previous finding of Pizzey et al. (1984) that Duchenne fibroblasts spread less well than normal fibroblasts after pre-incubation or plating with monensin, and possible explanations for this are discussed. The observations made are, however, consistent with the recent report that dystrophin is effectively not expressed in fibroblasts, and with the idea that the abnormal behaviour of endomysial fibroblasts in Duchenne dystrophy is a secondary consequence of their proximity to degenerating muscle. PMID- 2258387 TI - Extracts from eggs and oocytes of Xenopus laevis differ in their capacities for nuclear assembly and DNA replication. AB - We describe a cell-free extract derived from the oocytes of Xenopus laevis. The oocyte extract is capable of decondensing sperm chromatin and of replicating single-stranded DNA in a semiconservative, aphidicolin-sensitive manner. In addition, oocyte extract supports the elongation phase of DNA synthesis in nuclei that have been preinitiated for replication. All of these properties are shared by previously described egg extracts. However, oocyte extracts differ from egg extracts in two important ways. First, they cannot support nuclear assembly, as visualised by phase-contrast, fluorescence and electron microscopy. Second, they do not initiate replication on chromatin or nuclei de novo. Crude low-speed supernatants can be partially fractionated into soluble and vesicular components by high-speed centrifugation. Such fractions from eggs can be functionally reconstituted, but the oocyte soluble fraction does not acquire the ability to assemble nuclei, or replicate them, even when supplemented with the egg vesicular fraction. Similarly, oocyte vesicles cannot substitute for egg vesicles on reconstitution with the egg soluble fraction. When the requirement for nuclear assembly is bypassed by using preformed, quiescent nuclei, replication is observed in egg but not oocyte extracts. However, the oocyte extract is not inhibitory for initiation of replication, as it does not prevent replication of sperm nuclei when mixed with egg extract. We suggest that the different capabilities of egg and oocyte extracts could provide the basis of an assay system for identifying factors involved in the initiation of DNA replication. PMID- 2258388 TI - Spatial organization of repetitive DNA sequences in the bovine sperm nucleus. AB - During spermatogenesis, DNA in the sperm head becomes more tightly condensed as histones are replaced by protamine-like molecules. In this article, the question is asked whether, during the production of this highly differentiated cell, controls are imposed on the spatial organization of DNA within the nucleus. Heads from bull spermatozoa were isolated by a technique that removed the plasma membrane and acrosomal contents, and the DNA was induced to decondense by addition of 2-mercaptoethanol and trypsin. Under these conditions, decondensation was induced in all regions of the head. To determine whether there was any spatial restraint on packaging of the genome, three DNA probes were used (pl.709 512, containing an interspersed repetitive sequence; pCSIH, containing a copy of the major bovine centromeric statellite sequence; p18 s and p28 s, containing the 18 S and 28 S ribosomal genes) that might be expected to hybridize to different regions. Results showed that the interspersed repetitive probe hybridized to all regions of the head, whereas the ribosomal and centromeric probes hybridized to sequences that were largely confined to the equatorial region of the sperm. We conclude that organization of the genome in the bovine sperm nucleus is not random. PMID- 2258389 TI - Peroxisomes induced in Candida boidinii by methanol, oleic acid and D-alanine vary in metabolic function but share common integral membrane proteins. AB - Peroxisomes massively proliferate in the methylotrophic yeast Candida boidinii when cultured on methanol as the only carbon and energy source. These organelles contain enzymes that catalyze the initial reactions of methanol utilization. The membranes contain abundant proteins of unknown function; their apparent molecular masses are 20, 31, 32 and 47 x 10(3) Mr and are termed PMP20, PMPs31-32 and PMP47. Recently, we reported that peroxisomes in this yeast are also induced by oleic acid and D-alanine as carbon sources, and that these peroxisomes contain increased concentrations of the enzymes of fatty acid beta-oxidation or D-amino acid oxidase, respectively. This report extends these findings and further compares the enzyme composition from peroxisomes induced by methanol, oleic acid and D-alanine. the patterns of matrix proteins represented on SDS-polyacrylamide gels from peroxisomes induced by oleic acid or D-alanine were found to be very different from those of peroxisomes induced by methanol. In order to differentiate between membrane proteins that have specific functions in pathways of substrate utilization from those with more generalized functions, peroxisomal membranes from cultures grown on methanol, oleic acid or D-alanine were purified. Analysis of these fractions demonstrated that while PMP20 is found only in peroxisomes induced by methanol, the PMPs31-32 and PMP47 were the abundant peroxisomal membrane proteins (PMP) regardless of inducing substrate. The data strongly suggest that the function of PMP20 is related to methanol metabolism. In contrast, the functions of PMPs31-32 and PMP47 are 'substrate-nonspecific'. We speculate that they may relate to the structure, assembly or general function of the organelle. PMID- 2258390 TI - Microgravity decreases c-fos induction and serum response element activity. AB - Several studies have shown that altered gravity conditions influence mammalian cell growth and differentiation. The molecular mechanisms underlying these effects, however, remain relatively obscure. In this paper we show that microgravity reached in a sounding rocket strongly decreases epidermal growth factor (EGF)-induced expression of the proto-oncogenes c-fos and c-jun, which are both implicated in the regulation of proliferation and differentiation. Decreased activity of the serum response element (SRE), present in the c-fos promoter enhancer region, is probably responsible for the decrease in EGF-induced c-fos expression. In addition, we show that gravity alterations differentially modulate distinctive signal transduction pathways, indicating that gravity-dependent modulations of mammalian cell proliferation are unlikely to be caused by a nonspecific stress response of the cell. PMID- 2258391 TI - The role of differentiation in the suppression of malignancy. PMID- 2258393 TI - Kinetic analysis of mitotic spindle elongation in vitro. AB - Studies of mitotic spindle elongation in vitro using populations of diatom spindles visualized with immunofluorescence microscopy have shown that the two interdigitating half-spindles are driven apart by an ATP-dependent process that generates force in the zone of overlap between half-spindles. To characterize further the system responsible for spindle elongation, we observed spindle elongation directly with polarized light or phase-contrast video-microscopy. We report that the kinetics of spindle elongation versus time are linear. A constant rate of spindle elongation occurs despite the continuous decrease in length of the zone of overlap between half-spindles. The average rate of spindle elongation varies as a function of treatment, and rates measured match spindle elongation rates measured in vivo. When spindles elongated in the presence of polymerizing tubulin (from bovine brain), the extent of elongation was greater than the original zone of half-spindle overlap, but the rate of elongation was constant. No component of force due to tubulin polymerization was found. The total elongation observed in the presence of added tubulin could exceed a doubling of original spindle length, matching the elongation in the intact diatom. The linear rate of spindle elongation in vitro suggests that the force transducer for anaphase B is a mechanochemical ATPase, analogous to dynein or myosin, and that the force for spindle elongation does not arise from stored energy, e.g. in an elastic matrix in the midzone. Additionally, on the basis of observations described here, we conclude that the force-transduction system for spindle elongation must be able to remain in the zone of microtubule overlap during the sliding apart of half-spindles, and that the transducer can generate force between microtubules that are not strictly antiparallel. PMID- 2258392 TI - Synthetic epidermal pentapeptide and related growth regulatory peptides inhibit proliferation and enhance differentiation in primary and regenerating cultures of human epidermal keratinocytes. AB - A pentapeptide that inhibits proliferation of mouse epidermal keratinocytes in vivo and in vitro has been purified from mouse skin extracts. In the present study the effect of a synthetic analog of the epidermal pentapeptide on proliferation and differentiation of cultured human epidermal keratinocytes was investigated. In young, rapidly growing primary cultures the pentapeptide caused a dramatic decrease in mitotic activity and also induced pronounced changes in the balance between kinetically defined subpopulations of proliferating cells. A dipeptide derived from the pentapeptide was found to be at least as potent. A serine derivative of a hemoregulatory peptide also seemed to be active. When tested in epidermal cultures regenerating after removal of the suprabasal cell layers, both the pentapeptide and the dipeptide were shown to cause a delay in the proliferative response. Both peptides were also able to stimulate early (increase in cell size) and late (cornified envelope formation) events in the differentiation pathway of the keratinocyte. The apparent stimulatory effect on differentiation was most clearly seen in regenerating cultures, whereas the effect on primary cultures varied with the experimental set-up. It is suggested that homologous epidermal peptide(s) may play a major role in the regulation of human epidermal homeostasis. PMID- 2258394 TI - Identification of products formed during UV irradiation of tamoxifen and their use for fluorescence detection in high-performance liquid chromatography. AB - During the UV irradiation of tamoxifen, isomerization of the trans to the cis isomer takes place and consequently corresponding highly fluorescent phenanthrene derivatives are formed. Their formation can be used for the sensitive and selective detection of tamoxifen in high-performance liquid chromatography (HPLC). The structure of photoproducts was identified by 1H NMR spectroscopy, HPLC, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Owing to the variety of products formed and the higher selectivity and fluorescence response, on-line postcolumn photocyclization is preferred to the precolumn mode. A chromatographic system for the separation of isomers and photoproducts is suggested. PMID- 2258395 TI - Application of micro-scale liquid chromatography with fluorescence detection to the determination of thiols. AB - Different thiol compounds of biological and pharmacological interest were separated on a packed reversed-phase fused-silica capillary column and determined with fluorescence detection. Conventional inexpensive liquid chromatographic equipment could be adapted for such purposes, providing a highly efficient analytical system. The different compounds were derivatized with the fluorogenic reagents SBD-F and ABD-F and chromatographed both isocratically and in the gradient mode in order to separate a series of thiols with widely varying polarities. Subsequently the derivatives were measured at lambda ex. = 380 nm and lambda em. = 510 nm. Application of the system to biological and pharmacological samples is suggested. PMID- 2258396 TI - High-performance liquid affinity chromatography for the purification of immunoglobulin A from human serum using jacalin. AB - A high-performance liquid affinity chromatographic method for the purification of serum immunoglobulin A (IgA) using a jacalin column is described. The automated procedure takes about 2 with minimal manipulation. The yields of the isolated IgA and of its IgG and IgM contamination were studied by enzyme-linked immunosorbent assay (ELISA) of 30 sera. Purity was assured by immunoelectrophoresis. The ratio of IgA1 to total IgA was unchanged after purification, as verified by ELISA. The results showed that greater than 90% IgA could be recovered with less than 0.5% total IgG and greater than 2.0% total IgM remaining in the fractions containing purified IgA. PMID- 2258397 TI - Application of pyrolysis-high-resolution gas chromatography-pattern recognition to the identification of the Chinese traditional medicine mai dong. AB - Pyrolysis-high-resolution gas chromatography-pattern recognition (Py-HRGC-PaRe) was used to develop a potential technique for identifying the Chinese traditional medicine Mai Dong. About 1 mg of crude drug powder was pyrolysed in a furnace pyrolyser and the products were directly carried into a gas chromatograph with an FSOT capillary column (30 m x 0.265 mm I.D.) coated with DB-1701 (df 0.25 micron). The Py-HRGC data were analysed by non-linear mapping PaRe. The results showed that Mai Dong samples could be classified into two categories: Ophiopogon japonicus (L.f.) Ker-Gawl (included in the Chinese Pharmacopoeia) and Liriope spicata. PMID- 2258398 TI - Controlled thermal degradation for the identification and quantification of amine N-oxides in urine. AB - Studies of amine N-oxides in urine are important for the evaluation of occupational exposure to amines. These thermolabile compounds are difficult to handle by either gas or liquid chromatography, so a device for controlled thermal degradation has therefore been developed. It consists of a short precolumn with shut-off valves at both ends and an aluminum block for heating, and it was connected to the injection port of a gas chromatograph. After injection of amine N-oxides onto the precolumn and thermal degradation, the degradation products were allowed to enter the analytical column. Trimethylamine N-oxide (TMAO) and triethylamine N-oxide (TEAO) were investigated. Their thermal degradation patterns could be used for identification and quantification in aqueous solutions and in urine. Linear calibration graphs based on degradation product peaks (trimethylamine and O,N,N-trimethylhydroxylamine from TMAO and diethylamine and triethylamine from TEAO) were obtained for concentrations up to 500 ppm. Detection limits in aqueous solutions were 0.2 ppm (ca. 1 ng) for TMAO and 1 ppm for TEAO and the precisions were 6% and 9%, respectively. In urine, similar values were obtained for TEAO. The detection limit for TEAO corresponds to the expected concentration in urine after an 8-h exposure to air containing 0.8 mg/m3 of triethylamine. PMID- 2258399 TI - High-performance liquid chromatographic determination of several quinolone antibacterials in medicated fish feed. PMID- 2258401 TI - Water-soluble proteins do not bind octyl glucoside as judged by molecular sieve chromatographic techniques. AB - It is well known that the non-ionic detergent octyl glucoside (1-O-n-octyl-beta-D glucopyranoside) solubilizes biological membrane components. It forms complexes with membrane-spanning proteins by hydrophobic interactions and it forms mixed micelles with membrane lipids. In contrast, non-ionic detergents usually do not bind to water-soluble proteins. According to a recent report, substantial and cooperative binding of octyl glucoside to several water-soluble proteins does occur near the critical micelle concentration. However, data have been obtained that contradict this report. No decrease was found in the elution volumes of five water-soluble proteins on molecular sieve chromatography on two Superose columns in tandem when 35 mM octyl glucoside was included in the eluent. No binding of the detergent to these proteins was observed at 20 or 22.5 mM octyl glucoside on molecular sieve chromatography on a TSK SW guard column as determined by differential refractometry and UV spectrophotometry of the proteins in the absence or presence of octyl glucoside. The experiments were done with the same buffer system and with six of the proteins used in the reported study. It is concluded that, as expected, there is no binding of octyl glucoside to water soluble proteins above the detection limit (0.1 g detergent/g protein) of the refractometric method. The binding of, on average, 1.3 +/- 0.2 g of detergent per gram of water-soluble protein that was observed at 20 mM octyl glucoside in the reported study is not consistent with the present results. PMID- 2258400 TI - Ion chromatography of nitrite, bromide and nitrate ions in brine samples using a chloride-form anion-exchange resin column. PMID- 2258402 TI - Fractionation of basic nuclear proteins of human sperm by zinc chelate affinity chromatography. AB - Immobilized metal affinity chromatography was investigated for the fractionation of basic nuclear proteins of human sperm. Human sperm nuclei essentially contain two classes of protamines: a protamine of type P1 (HPl), rich in cysteine but with only one histidine, and three protamines of type P2 (HP2, HP3, HP4), rich in cysteine and histidine (nine in protamine HP2), potential ligands for transition metal ions. The critical conditions for metal affinity chromatography were defined: choice of metal, protein material and buffer, type of elution and sample loading. Chromatography of nuclear proteins, without histones and with cysteine residues alkylated by iodoacetamide, was optimum on zinc Chelating Sepharose in a Tris-acetate buffer and elution with an increasing concentration gradient of imidazole. Under these conditions, the two classes of protamines were completely separated. The intermediate basic proteins were further purified by reversed phase high-performance liquid chromatography. Heterogeneity of binding to zinc of protamine HP1 was demonstrated. The proposed method is simple and reproducible and the recovery of proteins is high. It may be applied to study the expression and function of P1 and P2 protamines, e.g., in the case of infertile men. PMID- 2258403 TI - Sensitive analysis of phospholipid molecular species by high-performance liquid chromatography using fluorescent naproxen derivatives of diacylglycerols. AB - A sensitive high-performance liquid chromatographic (HPLC) method for the separation and determination of diacylglycerophospholipid and diacylglycerol (DAG) molecular species has been developed. Phospholipids are hydrolysed with phospholipase C and the resulting DAGs are reacted with naproxen chloride in the presence of 4-dimethylaminopyridine. The naproxen-DAGs were purified by thin layer chromatography on silica gel G plates. Molecular species were separated using reversed-phase HPLC with isocratic elution and determined by measuring the absorbance at 230 nm or fluorescence at 352 nm (excitation at 332 nm). The method was applied to the determination of diacylglycerophosphoethanolamine in rat cerebrum and cerebellum. The molar absorption coefficient of the naproxen derivatives was 53,000 lmol-1 cm-1 at 230 nm, permitting the generation of linear concentration-dependent determinations down to less than 10 pmol. A ten-fold increase in sensitivity was obtained with a fluorescence detection system owing to the fluorescent properties of the proposed adduct. PMID- 2258404 TI - High-performance liquid chromatographic analysis of Romet-30 in salmon following administration of medicated feed. AB - A sensitive and selective high-performance liquid chromatographic assay was developed for the simultaneous quantitation of sulphadimethoxine (SDM) and ormetoprim (OMP) in chinook salmon muscle tissue. SDM and OMP were extracted from tissue samples using a solid-phase extraction technique. Resolution of both drugs was accomplished using an Ultrasphere ion-pair column (250 x 4.6 mm I.D.) and a mobile phase of acetonitrile-methanol-0.1 M phosphate buffer, pH 4 (17:10:73) with ultraviolet detection at 280 nm. The calibration curve in salmon muscle tissue was linear over the concentration range 0.2-20 ppm for both SDM (r2 = 0.9974) and OMP (r2 = 0.9956). The minimum detectable quantity of SDM and OMP in salmon muscle tissue was 0.2 ppm at a signal-to-noise ratio of 5:1. An in vivo feeding experiment was undertaken where chinook salmon were administered Romet-30 medicated feed for a 10-day period, followed by a 42-day wash-out period. The rate of tissue uptake and decline of SDM and OMP was shown to differ. PMID- 2258405 TI - Sample introduction in gas chromatography: simple method for the solventless introduction of crude samples of biological origin. PMID- 2258406 TI - Gas chromatographic and mass spectrometric determination of nitroaromatics in water. AB - Several methods for the extraction of nitroaromatic compounds from water were compared. High recoveries were achieved with discontinuous or continuous extraction of water with dichloromethane and by adsorption on Amberlite XAD-2, -4 and -8 resins (1:1:1) and elution with dichloromethane. The recoveries obtained with solid-phase extraction using cyano-, phenyl- or octadecyl-bonded phases varied, depending on the compounds studied, and were often low. Nitroaromatic compounds were determined by gas chromatography using an electron-capture or a chemiluminescence detector (thermal energy analyser) and by mass spectrometry using electron impact and positive- and negative-ion chemical ionization. PMID- 2258407 TI - Identification using solid phase extraction and gas chromatography-mass spectrometry of timolol in equine urine after intravenous administration. PMID- 2258408 TI - Essential oil from Thymus borgiae, a new Iberian species of the Hyphodromi section. PMID- 2258409 TI - High-performance liquid chromatographic method for the direct determination of the volatile anaesthetics halothane, isoflurane and enflurane in water and in physiological buffer solutions. PMID- 2258410 TI - Investigation of interfering products in the high-performance liquid chromatographic determination of polyamines as benzoyl derivatives. PMID- 2258411 TI - Determination of iodide in dairy products and table salt by ion chromatography with electrochemical detection. PMID- 2258412 TI - Determination of clenbuterol in bovine plasma and tissues by gas chromatography negative-ion chemical ionization mass spectrometry. AB - A highly sensitive and specific assay was developed for the determination of clenbuterol in bovine plasma and tissues. Clenbuterol and the internal standard [2H9]clenbuterol were measured by gas chromatography-negative-ion chemical ionization mass spectrometry with methane as the reagent gas. Bovine tissues including muscle, liver, heart, kidney, lung, suet, brain, spinal cord and thymus were ground in a buffer of pH 7 and then extracted using ethyl acetate. After two subsequent purification steps, the cleaned-up organic extract was derivatized with pentafluoropropionic anhydride. The mass spectrometer was set to monitor the abundant ions m/z 368 and 377 of the perfluoroacyl derivatives. This assay was performed with 1 ml of plasma or 0.2 g of tissue. The feasibility of this method was demonstrated by the determination of clenbuterol residues as the femtomole level in a variety of tissues. PMID- 2258413 TI - Gas chromatographic determination of phenol compounds with automatic extraction and derivatization. AB - Two gas chromatographic procedures for the determination of a variety of substituted phenols in water samples are described. The phenols were extracted or extracted-derivatized by using a continuous liquid-liquid extraction derivatization system and quantified with flame ionization detection. Ethyl acetate was found to be the most efficient solvent for phenols whereas n-hexane yielded essentially the same recoveries for derivatized phenols. Between 0.1 and 300 mg/l of the different phenols can be detected with a relative standard deviation 1.1 and 3.7%. The acetate esters of six phenols were formed by the direct addition of acetic anhydride to the organic extractant. The stable acetate esters thus formed were isolated by using a standard dimethyl polysiloxane gas chromatographic column. PMID- 2258415 TI - Chromatography of drugs and other toxic compounds. PMID- 2258414 TI - Surfactant-mediated hydrophobic interaction chromatography of proteins: gradient elution. AB - Addition of 3-[(3-cholamidopropyl)dimethylammonio]-l-propanesulphonate (CHAPS) to mobile phases in gradient elution hydrophobic interaction chromatography (HIC) on SynChropak Propyl causes changes in observed elution times for nine globular proteins. The nine proteins showed different percentage reductions in capacity factor, k', demonstrating the ability of CHAPS to change the selectivity of the separations. Three basic types of gradient experiments have been explored for surfactant-mediated gradient elution HIC. Type I gradients are conducted with constant salt and variable surfactant concentration. Type II gradients with variable salt and constant surfactant concentration, and Type III gradients with variable salt and surfactant concentrations. By the criterion of a linear relationship between gradient time and retention time the linear solvent strength condition applies to Type II and Type III gradients. Type III gradients, with the fastest re-equilibration time, are preferable for repetitive analyses. Type I gradients are relatively ineffective in making use of the solvent strength of CHAPS, and Types I and II gradients require long equilibration times due to large changes in surface concentration of CHAPS which occur during elution. The presence of CHAPS had a negligible effect on peak shapes of the proteins examined, except for bovine serum albumin which yielded a narrower, less distorted peak in the presence of CHAPS. PMID- 2258416 TI - Radiochromatography in pharmaceutical and biomedical analysis. AB - Recent advances in the chromatographic analysis of radiolabelled compounds are discussed, with emphasis on the optimization of radioactivity detection in modern chromatographic techniques. Applications are mentioned only infrequently. The state-of-the-art of common radioactivity detection methods is reviewed, as well as promising new detection principles. The latter include flow-through liquid scintillation counting of reversed-phase column eluates based on post-column extraction and solvent segmentation, flow-through heterogeneous counting using a flow cell constructed from axially aligned scintillation fibres, flow cells especially constructed for the detection of beta-emitting radioisotopes in capillary zone electrophoresis, position-sensitive analysers employed in radio planar chromatography and, finally 14C atom counting (as opposed to 14C decay counting) by accelerator mass spectrometry. PMID- 2258417 TI - Chromatography of calcium channel blockers. AB - Numerous publications during the past ten years have described the determination of various calcium channel blockers in biological fluids, using gas and liquid chromatographic techniques. Diltiazem, verapamil, flunarizine and a growing number of dihydropyridines belong to this group of drugs, which in most instances are active at low plasma concentrations. From a bioanalytical point of view these compounds have many features in common, such as high lipophilicity and favourable detection properties. PMID- 2258418 TI - Chromatography of cardiac glycosides. AB - Most of the recently reported methods for the quantitation of cardiac glycosides have been for digoxin and its metabolites. Recent procedures using high performance liquid chromatography-radioimmunoassay (HPLC-RIA) and HPLC following derivatization show appreciable improvements in accuracy and specificity for quantitating digoxin in the low nanogram range. Gas chromatographic procedures have been explored to a very limited extent and further advances in the quantitation of cardiac glycosides are anticipated to arise from the use of laser desorption-Fourier transform mass spectrometry. However, currently, HPLC with derivatization and HPLC-RIA techniques remain the techniques of choice for quantitation of digoxin and/or its metabolites based on considerations of ease of use, sensitivity, specificity, accuracy and reproducibility. PMID- 2258419 TI - Chromatographic analysis of anticancer drugs. AB - The present review on the methods for the analysis of anticancer drugs should be seen as an addition to the excellent work of Eksborg and Ehrsson published half a decade ago in this journal (Vol. 340, p.31). The style and format have been followed closely, with the focus again on chromatographic techniques. We felt it important to add a list of compound (group) structures as a service to the reader. Methods have been reviewed for alkylating agents, platinum compounds, antitumour antibiotics, antimetabolites, alkaloids, suramin, 1-hydroxy-3-amino propylidene-1,1-bisphosphonate and tamoxifen. PMID- 2258420 TI - Chromatographic methods for the bioanalysis of antiviral agents. AB - The present review has concentrated on chromatographic techniques for the quantitative determination of antiviral drugs in biological samples. Special attention has been paid to the elements of chromatographic assays that are essential to ensure selectivity, sensitivity, accuracy and precision of the various methods. Wherever possible, attempts have been made to determine the suitability of the methods for application to investigations in pharmacokinetics in man and experimental animals, biopharmaceutics, therapeutic drug monitoring, metabolism and pharmacology. Because of the serious consequences of infection from material contaminated with viruses, special consideration has been given to the handling of contaminated samples. It was convenient to divide the antiviral drugs for the purpose of this review into two groups, the nucleoside and the non nucleoside antiviral drugs. The nucleosides discussed are vidarabine, cytarabine, ribavirin, riboxamide, acyclovir, ganciclovir, desciclovir, carbovir, 2',3' dideoxyadenosine, 2',3'-dideoxycytidine, zidovudine, 2',3'-dideoxyinosine, 2',3' didehydro-3'-deoxythymidine, idoxuridine, 5-(2-bromovinyl)-2'-deoxyuridine, 2' fluoro-5-iodoaracytidine and 5-iodo-2'-deoxycytidine. The non-nucleoside antiviral drugs discussed are arildone, amantidine, rimantidine, moroxydine, enviroxime, foscarnet and ampligen. PMID- 2258421 TI - Analysis of drugs and other toxic substances in biological samples for pharmacokinetic studies. AB - The importance of the role of analysis of drugs and other toxic substances in biological samples (bioanalysis) in medicine, toxicology, pharmacology, forensic science, environmental research and other biomedical disciplines is self-evident. Among these disciplines, bioanalysis plays a special pivotal role in pharmacokinetics. The pharmacokinetic parameters, such as half-life, volume of distribution, clearance and bioavailability, of drugs and other compounds are derived from the concentrations of these analytes assayed in the biological samples collected at specified time points. The capability of analysts to develop sensitive and specific analytical methods for the assay of low concentrations of drugs and other toxic compounds in small amounts of biological samples has contributed significantly to the theoretical advances in pharmacokinetics and its applications in clinical pharmacology and the management of drug therapy in patients. The increased demands for pharmacokinetic applications in turn have stimulated the innovation and improvement in bioanalytical technologies. The reliability of the pharmacokinetic conclusions depends on the accuracy and precision of the analytical methods employed to assay the biological samples. Factors that affect the integrity of the bioanalytical data should therefore be controlled in analysis of biological samples for pharmacokinetics studies. The biological samples for drug concentration determination should be collected as specified in the study protocol with respect to the time and site of sampling. These samples should be processed to avoid extraneous interactions between the analytes and sampling devices or additives resulting in the redistribution of the analytes between components of the biological samples, such as displacement of drug binding and changes in the distribution of the analytes between plasma and red blood cells. The stability of the drugs and other analytes in the samples should also be evaluated to establish the conditions suitable for the transportation and storage of the samples to avoid chemical, photochemical and enzymatic degradation of the analytes. Various technologies have been utilized to assay biological samples for pharmacokinetic studies. The most frequently used are chromatography (high-performance liquid chromatography, gas chromatography and thin-layer chromatography), immunoassays and mass spectrometry.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258422 TI - Analysis of antiepileptic drugs. AB - This review discussed various analytical methods for the determination of antiepileptic drugs and their metabolites in biological tissues. The emphasis was on the reports published since their last review [J. T. Burke and J. P. Thenot, J. Chromatogr., 340 (1985) 199]. Both chromatographic and immunological procedure were cited and compared. Methods for individual and simultaneous quantitation of standard antiepileptic drugs and their metabolites were considered. In addition, a discussion of free drug determination and procedures for new candidate antiepileptic drugs were included. PMID- 2258423 TI - Chromatography of retinoids. AB - This article reviews the determination of retinoic acids and their metabolites (first-generation retinoids), aromatic retinoids (second generation) and arotinoids (third generation) in biological samples. Because of the sensitivity of the retinoids to isomerization and oxidation, special care has to be taken from sample collection and storage, throughout extraction, till the final chromatographic separation. High and strong protein binding, and insolubility in aqueous solutions hamper the extraction from biological samples. Various extraction procedures are discussed, mainly involving liquid-liquid extraction of biological fluids or lyophilized tissue samples. The new technique involving direct injection of biological fluids or tissue homogenates, using high performance liquid chromatography (HPLC) with automated column switching, provides full protection from light and simplifies sample work-up. HPLC with ultraviolet detection is the method of choice for the determination of retinoids, because it is rapid, sensitive and allows separation of geometric isomers and metabolites within a wide polarity range. Gas chromatography-mass spectrometry is not appropriate for first- and second-generation retinoids because of isomerization, but allows very sensitive determination of third-generation retinoids, although very extensive sample clean-up and derivatization are necessary. However, direct injection of large volumes of biological fluids into HPLC systems, using on-line solid-phase extraction and automated column switching, results in very sensitive methods even with simple ultraviolet detection and may become the method of choice for routine analyses. PMID- 2258424 TI - High-performance liquid chromatography of antibiotics. AB - High-performance liquid chromatographic (HPLC) monitoring of antimicrobial agents has recently become more widely used, and represents an interesting alternative to other methods. The methodology is characterized by good specificity and accuracy, and it is applicable to almost all antibiotics. This review first describes the successive steps to investigate for the development of an HPLC method for a new antibiotic, and how to make use of it. Particular emphasis is put on the problems related to the standardization of sample preparation and to the development of mobile phases for use with different molecules belonging to the same class. The second part of the review describes one or more HPLC techniques for a representative antibiotic of each major class. PMID- 2258425 TI - Separation procedures used to reveal and follow drug-protein binding. AB - The review gives a critical evaluation of the different separation procedures used to study drug-protein interactions and describes their various fields of application. For pharmacological studies, the most widely used methods are dialysis and ultrafiltration, because they allow measurements with solutions of high protein concentrations, such as those found in therapeutic conditions. Both techniques use membrane devices, which may induce additional binding effects. Another drawback of these techniques is the need for radiolabelled compounds. Chromatographic methods, which now take advantage of the technology of high performance liquid chromatography, are generally faster and do not use drug labelling because of the higher sensitivities of the detectors. Two different approaches are possible: either all the interacting species (protein and drug) are dissolved in the mobile phase, or one of them (protein or drug) is immobilized on the support. Several chromatographic methods are available for studies in solution that differ according to the sample injection mode (frontal or zonal elution) and the nature of the mobile phase used. They include quantitation of the drug-protein complex by zonal elution, the Hummel and Dreyer method, frontal elution, the vacancy peak method, and retention analysis by zonal elution. Frontal elution is the most rigorous method since all the species at equilibrium are present in the mobile phase with known and constant concentrations. The most promising one is the Hummel and Dreyer method, because of the very small amount of protein injected in the mobile phase containing the drug. Drug-protein interactions may be studied by affinity chromatography by immobilizing one of the interacting species on the support. Comparison of the constants obtained with methods when both the drug and the protein are in solution is questionable, since the immobilized species in affinity separations differ in their physical properties from those in solution. The main advantage with studies on immobilized proteins is the easy comparison of the binding properties of various drugs, especially when they are enantiomeric. The results of the binding constants measured by different separation methods are given for the albumin-phenylbutazone and albumin-warfarin systems. Good agreement is generally obtained, which proves the validity of using chromatography as a tool to study drug-protein interactions. PMID- 2258426 TI - Application of micellar mobile phases for the assay of drugs in biological fluids. AB - Although micellar chromatography has been used for the determination of drugs in biological fluids since 1985, relatively few researchers have applied the technique to therapeutic monitoring. The reasons for this are rather unclear. It may be that most of the present extraction/reconstitution techniques are well established or that the method development procedure is unfamiliar. Significantly lower detection limits can be obtained with micellar mobile phases and column switching than with micellar mobile phases alone. Only two groups have used micellar mobile phases in conjunction with column switching for the determination of drugs in biological fluids. Since column switching with micellar mobile phases is a relatively new and untried technique, it will take some time before the full range of its applicability and limitations are known. PMID- 2258427 TI - Mixed speech dominance in the Intracarotid Sodium Amytal Procedure: validity and criteria issues. AB - An international survey was conducted of 55 epilepsy surgery programs (from 10 countries) that conduct the Intracarotid Sodium Amytal Procedure (IAP). Respondents reported large differences in the prevalence of mixed speech dominance (MSD) in their patient populations. These differences are shown to be due in part to disagreement about the criteria for the demonstration of speech production from the non-speech-dominant hemisphere. The disagreement may be related to differences in the administration and interpretation of the IAP as well as the validity of the construct of MSD. The prevalence of MSD in various patient populations cannot be determined until standard procedures for the administration of the IAP are adopted and until the validity of criteria for MSD is demonstrated. Clinical implications of these results are discussed. PMID- 2258428 TI - Generalized cognitive function after stroke. AB - The present investigation was designed to determine the effect of cerebrovascular lesions upon general neuropsychological function. The performances of 60 patients with lateralized or diffuse cerebrovascular lesions were compared to 20 controls on cognitive and intellectual measures. Multivariate analyses indicated markedly poorer performances by the cerebrovascular groups on measures of generalized cerebral function, and no differences on such measures were found between the left- and right-damaged groups. The lateralized CVD groups demonstrated a differential tendency towards lower performances on VIQ for the left group and on PIQ for the right group. The results indicate significant neuropsychological impairment which extends beyond the expected lateralized dysfunctions, or selected deficits, associated with the damaged hemisphere. These findings indicate the importance of evaluating generalized as well as specific cognitive functions in clinical assessment of cerebrovascular lesions. PMID- 2258429 TI - Antidepressant effect on memory in depressed older persons. AB - There is evidence from the clinical and experimental literature that the elderly may be more susceptible to the anticholinergic side effects associated with antidepressant drugs. Fifty-four elderly depressed subjects participated: 27 were taking antidepressants and 27 were unmedicated controls matched for severity of depression, age, and education. The medicated subjects showed a mild, but statistically significant, deficit on a set of six measures of memory performance. However, it was unclear whether this deficit was related to anticholinergic activity. It appears that, while antidepressant medications may not be benign in terms of memory functioning in the elderly, the memory difficulties are mild and are not similar to those of Alzheimer's patients. Thus, differential diagnosis of depression and dementia should not be greatly complicated by antidepressant medication. PMID- 2258431 TI - Line orientation judgment in normal elderly and subjects with dementia of Alzheimer's type. AB - Ninety-five normal controls divided into three subgroups (55-64 yrs, 65-74 yrs, and 75-84 yrs) and 11 subjects with early dementia of Alzheimer's type (DAT) were given a line orientation judgment task (Benton, Varney, & Hamsher, 1978). No difference appeared between the three control subgroups in global score but the difference between controls and DAT subjects was significant. However, some DAT subjects had a global score overlapping the scores of controls. Error types were also analyzed. Results of this analysis showed that some errors appeared in all subjects, normal and DAT, while others were specific to DAT subjects. It was speculated that these error types were a manifestation of a deeper visuospatial deficit, revealing a major problem of the DAT in spatial organization. Thus, this study suggests that an analysis of the error types observed in the line orientation judgment task may be helpful in differentiating normal elderly from early DAT. PMID- 2258430 TI - Occupational neurotoxicology: some neuropsychological issues and challenges. AB - Occupational neurotoxicology offers the opportunity for demonstration of neuropsychological capacity to detect otherwise non-demonstrable CNS compromise, and thereby the enhancement of human well-being. Simultaneously, neuropsychological applications in this field highlight some of the disciplines persisting problems, such as uncertainties over the differential sensitivities of tests, lack of a common functional taxonomy, limited employment of component analysis procedures, insufficiencies of control over extraneous variance (including malingering and social expectancy effects), and knowledge limits regarding the everyday significance of findings. These problems are especially troublesome where effects are subtle, diffuse, or of insidious onset, and where physically demonstrable lesioning is uncommon. With neuroimaging advances, conditions so characterized may become increasingly the focus of neuropsychological efforts. The likelihood of increasing involvement with legal issues such as compensation makes awareness of these difficulties, and concerted efforts to resolve them, crucial. PMID- 2258433 TI - Prospects for faking believable memory deficits on neuropsychological tests and the use of incentives in simulation research. AB - The vulnerability of several neuropsychological memory tests--the Wechsler Memory Scale--Revised, Complex Figure Test, Auditory Verbal Learning Test, and Rey Memory Test--to faked deficits was evaluated. Subjects were randomly assigned to one of three conditions: Control (n = 28), Malingering with a financial incentive (n = 30), and Malingering without a financial incentive (n = 28). Overall, the performance of the Malingering Groups was not significantly different from one another, but both groups were significantly poorer than Controls. Discriminant functions with a reduced set of predictors correctly classified about 75% of cases in both the Control and the combined Malingering Groups on cross validation. The results suggest that neuropsychological memory tests are vulnerable to faked deficits, and that recognition tasks are disproportionately affected. The use of incentives in simulation research is also discussed. PMID- 2258432 TI - Recovery of orientation following closed-head injury. AB - The pattern of recovery of orientation to person, place, and time was investigated in 84 patients who were initially disoriented while hospitalized on the neurosurgery service after sustaining a closed-head injury (CHI) of varying severity. Results of daily administration of the Galveston Orientation and Amnesia Test revealed that the most common sequence of recovery of orientation was person, place, and time: accounting for about 70% of the patients. Return of orientation to time preceded reorientation to place in 13% of the patients while other orderings of reorientation were present in 11% of the cases. Temporal disorientation was initially characterized by backward displacement of the date from the actual date in 68% of the patients. The magnitude of this displacement progressively shrank as the patients became more oriented. Patients who exhibited the greatest backward displacement of the date had more severe and persistent impaired consciousness, were older and had longer durations of posttraumatic amnesia. These data support Ribot's hypothesis that older memories are relatively resistant to cerebral insult. PMID- 2258434 TI - Stroop Color-Word Test performance in patients with Alzheimer's disease. AB - Patients with Alzheimer's disease (AD) (n = 36) and normal older adults (n = 36) were individually administered the Stroop Color-Word Test. Eight of 36 (22%) AD patients exhibited confusion between the colors blue and green, while no control subject had difficulty distinguishing among the colors. In a second experiment, a subset of the original sample (15 AD patients and 8 control subjects) was retested using the Stroop. Only 2 AD patients showed color confusion on both test occasions, while 7 AD patients exhibited color confusion on one occasion. No control subject exhibited confusion between colors the second time. These results indicate that color confusion in AD patients is inconsistent. Due to the high incidence of color confusion in AD patients, the Stroop should be used with caution in patient populations. PMID- 2258435 TI - A WAIS-R marker for accelerated aging and dementia, Alzheimer's type? Base rates of the Fuld formula in the WAIS-R standardization sample. AB - Recent reports have provided evidence that a WAIS-R marker for dementia of the Alzheimer's type (DAT) may have value in differential clinical diagnosis. Using the Fuld (1984) formula, this study investigated the prevalence of the WAIS-R marker in the WAIS-R standardization sample (N = 1,880), whose members range in age from 16 to 74 years. The results from the WAIS-R sample suggest no significant age differences in the occurrence of this marker when age-corrected scaled scores are employed. Across age, the occurrence of this marker is about 6.2%. Although there were no significant effects according to race, there were significant sex (males = 7.34%; females = 5.11%) and education effects. For individuals aged 65-74 with some post high school education, the base rate was about 14%. These findings are discussed as they relate to the potential clinical usefulness of this marker in the differential diagnosis of DAT. PMID- 2258436 TI - Early HIV-related neuropsychological impairment: relationship to stage of viral infection. AB - Sixty male outpatients with no past neuropsychiatric history were examined for evidence of early HIV-related neuropsychological impairment. Significant cognitive deficit, as measured by the RAVLT and WAIS-R Digit Symbol Substitution tests, and moderate correlation with indices of immune function, were observed in a group of patients with AIDS-Related Complex [ARC]. Patients with asymptomatic HIV-infection demonstrated no significant differences in performance compared to a group of HIV-seronegative controls. No significant group differences in age, education, predicted-IQ or self-rated depression and anxiety were observed. These results support the hypothesis that HIV-related cognitive disturbance occurs within the context of immunosuppression. PMID- 2258437 TI - Effects of chronic alcoholism on hemispheric functioning: an examination of gender differences for cognitive and dichotic listening tasks. AB - A pattern of intact verbal abilities and impaired visuospatial abilities has led to a hypothesis of alcohol-induced right-hemisphere dysfunction in male chronic alcoholics. The applicability of this hypothesis to chronic female alcoholics was examined by administering the WAIS-R, Stark Paired Associates Tasks, and dichotic listening tasks to 15 male and 10 female alcoholics and 15 male and 10 female controls of similar age and education. Alcoholics had significantly lower Full Scale IQ scores on the WAIS-R but neither sex had a Verbal-Performance IQ difference indicative of right-hemisphere dysfunction. Male alcoholics showed deficits on both the Verbal and Visuospatial Stark Tasks, the deficit being greater on the Visuospatial Task. Male alcoholics showed an increased right-ear superiority on the verbal dichotic listening task and a decreased left-ear superiority on the musical dichotic listening task, both indicative of right hemisphere dysfunction. The results, except for the WAIS-R, support the hypothesis that male but not female chronic alcoholics exhibit right-hemisphere dysfunction. Females, alcoholic or not, appear to be less lateralized in function. PMID- 2258438 TI - Psychosis following styrene exposure: a case report of neuropsychological sequelae. AB - A patient with a significant history of substance abuse was exposed to styrene and other solvents in the workplace. He became acutely psychotic, experiencing visual hallucinations. The psychosis was controlled with neuroleptic medications and avoidance of solvent exposure, but he continued to show significant deficits in visual-spatial and memory abilities. These deficits cleared with time away from the workplace. The case is of interest in terms of neuropsychological sequelae of solvent exposure and potential interaction of solvents with alcohol and recreational drugs. PMID- 2258439 TI - Incidence of the WAIS-R Fuld profile in HIV-1 infection. AB - The incidence of a WAIS-R subtest "marker" sensitive to cholinergic dysfunction was assessed in a sample 116 homosexual males infected with HIV (Acquired Immunodeficiency Syndrome [AIDS] N = 40; AIDS Related Complex [ARC], N = 76). The incidence of positive profiles was low in the overall sample (11/116, 9%), and significantly lower than incidence rates reported for known cholinergic deficient groups (Alzheimer's disease; scopolamine). However, significantly more AIDS patients (8/40, 20%) than ARC patients (3/76, 4%) demonstrated positive profiles. These results suggest that, as a group, persons with ARC or AIDS do not show an increased incidence of the Fuld profile associated with cholinergic disruption, and offer continued support for diagnostic specificity of the Fuld formula for Alzheimer's disease. PMID- 2258440 TI - Growth parameters and attention to faces at 4 to 6 months of age. AB - Duration of attention to faces and response decrement were studied in 57 full term infants between 15.1 and 28.5 weeks of age during a health maintenance clinic visit. Six measures of growth, obtained from the medical record, included weight, length, and head circumference at birth, and weight, length, and head circumference at the time of the clinic visit. Correlation analysis revealed that longer average initial fixation time was associated with male sex, shorter birth length, and larger ponderal index. Multiple regression analysis indicated that together these three variables accounted for 17% of the variance in average initial fixation time (p less than 0.05). Length at the time of the health maintenance visit and male sex also were associated with longer average initial fixation time and, together, accounted for 13% of the variance (p less than 0.05). Response decrement was larger in children with larger head circumference at birth, in girls, and in infants with a larger ponderal index at birth. Together, these three variables accounted for 27% of the variance (p less than 0.001). Results suggest that more efficient processing of visual information may be related to neurophysiological maturity at term, and raises the possibility that neurophysiological maturity may account for a substantial portion of the correlation between attention behavior and later intelligence. PMID- 2258441 TI - Ethnicity, infant-feeding practices, and childhood adiposity. AB - There has been professional concern that the type of milk used for infant-feeding may lead to adiposity. Studies of the relationship between infant milk-feeding and adiposity, however, have led to inconsistent results. This study investigated the relationship of infant-feeding practices to three indicators of adiposity: body weight, body mass index (BMI) and sum of seven skinfolds. The sample includes children at 3 or 4 years of age, in three ethnic groups. Multivariate techniques assessed the relationship among practices of infant-feeding with three indicators of adiposity, while considering potential confounding variables. Although a weak bivariate relationship was detected between the duration of breastfeeding and body weight, none of the measures of infant-feeding were related to the three indicators of adiposity. Black-American girls had smaller skinfolds than Anglo- or Mexican-American girls, with no ethnic group differences among boys. Concerns about adiposity due to methods of infant-feeding can be allayed, at least among 3- or 4-year-old children. PMID- 2258442 TI - Sleep enhanced and irritability reduced in preterm infants: differential efficacy of three types of waterbeds. AB - The purpose of this study was to determine whether waterbeds enhance preterm infants' sleep and reduce irritability, and whether plain, continuously, or intermittently oscillating waterbeds are differentially effective in producing these effects. The baseline states and motility of 52 stable preterm infants were assessed on two consecutive days for 100 minutes each. The infants then were randomly assigned to four groups: a control group who remained on the incubator mattress, or to one of the three experimental groups, each using a different waterbed. On days 3 and 4 in the assigned test condition, the infants' states and motility were again assessed for 100 minutes each day. The results indicate that, compared with infants in the control group, infants assigned to any of the waterbed groups slept significantly more and better, had significantly fewer unsmooth movements, state changes, and transitional states, and were significantly less irritable. Differential treatment effects were found, with infants on continuously oscillating waterbeds showing the most marked reductions in irritability, restlessness, state changes, and unsmooth movements. Thus, to enhance restful sleep and to reduce irritability and/or restlessness, it would be clinically advantageous to use waterbeds in the care of preterm infants. Since even the simple, nonoscillating waterbed improved sleep and reduced restlessness, the use of these beds would be the least costly to achieve these effects. PMID- 2258444 TI - Munchausen syndrome by proxy presenting as a developmental disability. AB - Munchausen syndrome by proxy (MSBP) is a form of child abuse in which a parent falsifies illness in a child by fabricating or producing symptoms and presenting the child for medical care while disclaiming knowledge as to the cause of the problem. This report presents the case history of a child diagnosed with MSBP who was portrayed as having multiple developmental disabilities by her mother. Three elements of the case are noteworthy. The emphasis by the mother on multiple developmental disabilities has not been reported. The complexity of this case is unusual and may reflect the complexity of the mother's psychopathology. The interdisciplinary team evaluation was instrumental in making the diagnosis. PMID- 2258443 TI - The impact of school-based education on the young child's understanding of death. AB - The young child's immature understanding of the concepts related to death serves to heighten anxiety about death and interferes with successful adjustment to loss. This study was a randomized trial of the efficacy of a 3-week school-based educational program in the promotion of the concepts of death in 4- to 8-year-old children (prekindergarten through second grade). The Smilansky Death Concept Questionnaire, a validated and published structured interview, was administered pre- and postintervention phase to all study participants (N = 184). The experimental group received three interventions: (1) a series of six 30 to 45 minute presentations about concepts of death, (2) teacher educational presentation, and (3) parent educational presentation. Significant mean gains were noted for the experimental group as compared to the control group in the total death concept score, the total score for human death, the total score for animal death, and two of the four factors studied, that of causality and that of inevitability and old age. The gain in total death concept score as a result of the 3-week educational program was equivalent to the amount of conceptual development that is seen in one year in the absence of intervention. PMID- 2258445 TI - Early intervention in the context of foster care. AB - There may be a number of specific foster care models that would facilitate infant development. The important point is that the emphasis should shift from foster care as maintenance to foster care as active intervention. Several other recent developments in public policy and public opinion suggest that the time is ripe for such a change; the federal government has mandated provision of early intervention services for young children at risk, and there is renewed interest in breaking the cycle of disadvantage. At this point, we must deal with the reality of the large number of infants and young children who enter the foster care system and who stay for substantial periods of time. This situation represents an opportunity for professionals and foster parents alike to play a crucial role in changing the potentially adverse course of development for many children. It is an opportunity too important to be lost. PMID- 2258446 TI - The recognition of psychosocial disorders in pediatric office practice: the current status of the pediatric symptom checklist. PMID- 2258447 TI - Lithium and the newborn heart. PMID- 2258448 TI - Fenfluramine augmentation in tricyclic-refractory depression. AB - The clinical efficacy of lithium augmentation in refractory depression is hypothesized to depend on the ability of lithium to enhance presynaptic 5 hydroxytryptamine (5-HT) function. Since fenfluramine promotes release and inhibits reuptake of presynaptic 5-HT, we assessed its efficacy in augmenting ongoing tricyclic antidepressant treatment of refractory depression. Fifteen patients with DSM-III major depression failed to respond to treatment with desipramine 2.5 mg/kg/day or more (plasma levels of at least 125 ng/ml) given for at least 4 weeks. Fenfluramine 40-120 mg/day was then added to the ongoing desipramine in a placebo substitution design. There was no statistically significant evidence of either transient or sustained clinical improvement during the 2 weeks of fenfluramine augmentation. One patient appeared to respond to the treatment, but one appeared to worsen. Fenfluramine more than doubled steady state plasma levels of desipramine. These findings suggest that lithium's efficacy as an augmenting agent depends on properties that are not shared by fenfluramine. Fenfluramine cannot be recommended in the routine management of refractory depression. PMID- 2258449 TI - Relationship of hydroxynortriptyline to nortriptyline concentration and creatinine clearance in depressed elderly outpatients. AB - Plasma concentration of E-10-hydroxynortriptyline is increased in the elderly and may be related to both renal clearance of hydroxynortriptyline and rate of liver hydroxylation of nortriptyline. In 25 ambulatory, depressed elderly outpatients treated with therapeutic doses of nortriptyline, relationships among plasma levels of nortriptyline and E-10-hydroxynortriptyline, and an estimate of creatinine clearance were examined. Plasma levels of E-10-hydroxynortriptyline (corrected for varying dosage) were significantly correlated with age and inversely correlated (r = -0.50) with creatinine clearance but not with notriptyline or Z-10-hydroxynortriptyline concentration. E-10 hydroxynortriptyline concentration was about 5 1/2 times that of Z-10 hydroxynortriptyline. By best subsets multiple regression analyses, the ratio of E-10-hydroxynortriptyline to nortriptyline level was best predicted by plasma nortriptyline concentration, creatinine clearance, and age, all of which accounted for 63% of the variance. These results corroborate and extend previous findings in elderly inpatients in whom creatinine clearance was measured directly. In addition, age had an effect on E-10-hydroxynortriptyline independently of creatinine clearance. Since E-10-hydroxynortriptyline concentration has been related to both therapeutic efficacy and toxicity during nortriptyline treatment, it may be important to assess nortriptyline hydroxymetabolites in elderly patients and in those with renal insufficiency. PMID- 2258451 TI - Lithium interactions: lithium and electroconvulsive therapy. PMID- 2258450 TI - Amoxapine versus amitriptyline for continuation therapy of depression. AB - The efficacy of continuation therapy with tricyclic antidepressants has been established in a number of controlled trials. This study investigated the efficacy of continuation therapy with a relatively new antidepressant, amoxapine, using a double-blind controlled comparison with amitriptyline. Subjects met DSM III criteria for major depressive disorder and were randomized to treatment with either amoxapine 400 mg (N = 47) or amitriptyline 300 mg (N = 45). The acute phase lasted up to 8 weeks. Responders were continued on the same drug at the same dose for a 16-week continuation phase. Some measures found more rapid onset for amitriptyline, which is inconsistent with findings from some prior studies. Amitriptyline was more effective in inducing full recovery. There was a trend for higher relapse rates on amoxapine, perhaps related to the fact that there were more partial responders entering continuation therapy from this group. Side effect rates were equivalent in the two drugs. However, physicians rated amoxapine's side effects as more frequently interfering with its therapeutic effect. These data suggest that amoxapine does not offer any clear advantage over amitriptyline for continuation therapy in patients who have major depressive disorder. Of potential clinical relevance is the finding that achieving full recovery in the acute phase may reduce the likelihood of relapse in the continuation phase, regardless of the type of antidepressant medication prescribed. PMID- 2258452 TI - The clinical significance of lithium-nonsteroidal anti-inflammatory drug interactions. AB - There is conclusive evidence that nonsteroidal anti-inflammatory drugs can increase serum lithium levels, diminish renal lithium clearance, and possibly induce lithium toxicity. Such an interaction has occurred in patients with normal renal function. The effect on serum lithium levels varies greatly among different nonsteroidal anti-inflammatory drugs, indomethacin seeming most potent. On the other hand, there is no convincing evidence that sulindac and aspirin affect serum lithium levels to a clinically significant degree. Ibuprofen and naproxen can significantly increase serum lithium levels, but there is marked interindividual variation. Patients receiving nonsteroidal anti-inflammatory drugs must have their serum lithium levels checked every 4-5 days until the extent of drug interaction is assessed. A reduction in lithium dosage may be needed in some cases. PMID- 2258454 TI - Fluoxetine treatment of impulsive aggression in DSM-III-R personality disorder patients. PMID- 2258453 TI - Possible influence of carbamazepine on plasma imipramine concentrations in children with attention deficit hyperactivity disorder. AB - The effect of carbamazepine on the plasma concentration of imipramine and its metabolite desipramine was examined retrospectively in 36 sex- and age-matched children with attention deficit hyperactivity disorder. One-half of the children received imipramine and the other half received combined carbamazepine and imipramine for 1-6 months. The imipramine dosage was significantly higher in the combined treatment group than in the imipramine-only group. Despite receiving larger doses, the combined treatment group had significantly lower mean levels of imipramine, desipramine, and total tricyclic antidepressant compared with those children receiving imipramine alone. Lowered plasma concentrations of tricyclic antidepressants with carbamazepine coadministration have not been reported previously. Although more rigorous studies are needed to confirm these findings, our data suggest that increased imipramine doses may be necessary for adequate response in children on combined therapy. Moreover, toxicity could result upon withdrawal without imipramine dosage adjustment. PMID- 2258455 TI - Clomipramine treatment of possible atypical obsessive-compulsive disorder. PMID- 2258456 TI - Paradoxical reaction to buspirone augmentation of fluoxetine. PMID- 2258457 TI - Diltiazem effect on carbamazepine levels in manic depression. PMID- 2258459 TI - Possible adverse drug interactions between fluoxetine and other psychotropics. PMID- 2258458 TI - Possible adverse effects of buspirone when used with other psychotropic drugs. PMID- 2258460 TI - Increase of spontaneous blink associated with extrapyramidal side effects: a case report. PMID- 2258461 TI - Light microscopic and ultrastructural analysis of GABA-immunoreactive profiles in the monkey spinal cord. AB - It is hypothesized that terminals containing gamma-aminobutyric acid (GABA) participate in presynaptic inhibition of primary afferents. To date, few convincing GABA-immunoreactive (GABA-IR) axo-axonic synapses have been demonstrated in support of this theory. The goal of this study is to document the relationship between GABA-IR profiles and central terminals in glomerular complexes in lumbar cord of the monkey (Macaca fascicularis). In addition, the relationship between GABA-IR profiles and other neural elements are analyzed in order to better understand the processing of sensory input in the spinal cord. GABA-IR cell bodies were present in Lissauer's tract (LT) and in all laminae in the spinal gray matter except lamina IX. GABA-IR fibers and terminals were heavily concentrated in LT; laminae I, II, and III; and present in moderate concentration in the deeper laminae of the dorsal horn, ventral horn (especially in association with presumed motor neurons), and lamina X. Electron microscopic analysis confined to LT and laminae I, II, and III demonstrated GABA-IR cell bodies, dendrites, and myelinated and unmyelinated fibers. GABA-IR cell bodies received sparse synaptic input, some of which was immunoreactive for GABA. The majority of the synaptic input to GABA-IR neurons occurred at the dendritic level. Furthermore, the presence of numerous vesicle-containing GABA-IR dendrites making synaptic interactions indicated that GABA-IR dendrites also provided a major site of output. Two consistent arrangements were observed in laminae I-III concerning vesicle-containing GABA-IR dendrites: 1) they were often postsynaptic to central terminals and 2) they participated in reciprocal synapses. The majority of GABA-IR axon terminals observed contained round clear vesicles and varying numbers of dense core vesicles. Only on rare occasions were GABA-IR terminals with flattened vesicles observed. GABA-IR terminals were not observed as presynaptic elements in axo-axonic synapses; however, on some occasions, GABA IR profiles presumed to be axon terminals were observed postsynaptic to large glomerular type terminals. Our findings suggest that a frequent synaptic arrangement exists in which primary afferent terminals relay sensory information into a GABAergic system for further processing. Furthermore, GABA-IR dendrites appear to be the major source of input and output for this inhibitory system. The implications of this GABAergic neurocircuitry are discussed in relation to the processing of sensory input in the superficial dorsal horn and in terms of mechanisms of primary afferent depolarization (PAD). PMID- 2258462 TI - Development of connections to and from the visual cortex in the wallaby (Macropus eugenii). AB - The time course of the development of connections between the visual cortex and the main subcortical visual structures, as well as intrahemispheric and interhemispheric connections, has been studied in the marsupial wallaby (Macropus eugenii) to compare its development with that of placental mammals. Pouch young are born prior to retinal innervation of the primary visual centers and spend a protracted period of development in the pouch, making them ideal for visual, developmental studies. Horseradish peroxidase conjugated to wheatgerm agglutinin was injected into either the presumptive visual cortex or the superior colliculus in young of varying ages. Thalamocortical projections from the dorsal lateral geniculate and lateral posterior nuclei reach the presumptive visual cortex between 12 and 15 days after birth. Descending cortical connections form later. Corticogeniculate axons are first detected in the geniculate and lateral posterior nucleus at 48 days after birth, while corticocollicular axons first reach the superior colliculus at 71 days and, by 81 days, have innervated the superficial layers. Intrahemispheric and interhemispheric connections form even later. By 99 days intrahemispheric axons from area 17 have accumulated in visual association areas but are yet to invade layers III and IV, their major termination zones in adult, while axons projecting back to area 17 have also reached their target area. At this time interhemispheric axons from area 17 have begun to accumulate in the opposite visual cortex, although they have not invaded the cortical layers. By 111 days cortical cells projecting to the opposite visual cortex are first labelled. These have a more widespread distribution in area 17 at 111 and 122 days compared to the adult, where they are confined to the 17/18 border. The results show that the marsupial wallaby has a timetable of similar sequence, but different relative timing, in the formation of cortical connections compared to that of placental mammals. In the first half of the period between conception and eye opening, the timing in the wallaby precedes considerably that in placental mammals. Ascending connections from the thalamus develop relatively earlier in the wallaby but descending collicular connections are delayed until the same relative time that they appear in placental mammals. PMID- 2258463 TI - Cytoarchitectonic atlas of the cochlear nucleus of the chinchilla, Chinchilla laniger. AB - A detailed cytoarchitectonic atlas of the chinchilla cochlear nucleus complex was prepared in the transverse plane with the Nissl method. Subdivisions of the cochlear nucleus were defined on the basis of cell size, cell packing density, and, in some cases, on cytological features of cell types. In general, the chinchilla cochlear nucleus has an organizational plan similar to that described for other mammalian species. As in other rodents, the chinchilla has a large and well-developed dorsal cochlear nucleus consisting of three distinct layers. The ventral cochlear nucleus consists of two distinct nuclear masses, a posterior nuclear group and an anterior nuclear group, each composed of several subdivisions, which are qualitatively similar to those described for other mammals. Thus it is now possible to compare detailed observations, such as tonotopic maps, in the chinchilla with findings from the analogous cell populations in other mammals, such as the cat, with considerable precision. In the chinchilla, three cell groups, previously undescribed in mammals, have been defined and their counterparts in the cat identified. PMID- 2258464 TI - Renal ultrastructure in lamb nephrosis. AB - Ultrastructural investigation of the kidneys of 18 lambs with clinical nephrosis revealed that groups of tubules showing various degrees of degeneration up to necrosis could exist alongside tubules showing proliferative or regenerative changes. Lesions were most common in proximal convoluted tubules, less common in distal tubules and absent from collecting ducts or straight tubules, though the latter were often distended with hyaline or flocculent casts. The basement membranes of necrotic tubules were intact, suggesting that the potential for regeneration was unimpaired. Nine lambs had lesions in the glomeruli, though the distribution was focal. Glomerular lesions occasionally were acute and degenerative but more usually were proliferative, with occlusion of capillaries due to endothelial swelling and mesangial encroachment. Basement membrane splitting or reduplication was a feature of some glomeruli, but neither subepithelial nor subendothelial dense deposits were seen. The changes were consistent with damage by an unknown nephrotoxic factor or factors. PMID- 2258465 TI - Histopathology of oesophagogastric lesions in pigs. AB - The development of parakeratotic lesions and ulcers of the oesophagogastric epithelium was studied in pigs from a variety of sources and of ages ranging from 10 to 22 weeks. In general, the severity, as assessed by gross appearance, paralleled the depth to which parakeratotic change extended into the epithelium. However, some early degenerative change and erosion was observed in epithelium graded as macroscopically normal. Separation and erosion usually occurred beneath a band of epithelial cells with cytoplasmic pallor and nuclear degeneration underlying the parakeratotic layers. These findings are discussed in relation to the possible role of diet and gastric acidity in the pathogenesis of the lesions. PMID- 2258466 TI - Pathological and immunohistochemical studies of follicular lymphoma in two calves. AB - Pathological and immunohistochemical studies were performed on two cases of bovine follicular lymphoma with severe leukaemia and antibodies to bovine leukaemia virus. Histologically, numerous neoplastic follicular structures were observed in the lymph nodes and spleen of both cases and in the tonsils and Peyer's patches of one case. The neoplastic cells infiltrated diffusely into the liver, lungs and heart in both cases and into the tonsils, kidneys, abomasum and bone marrow in one case. Intracytoplasmic immunoglobulin was negative in the neoplastic cells. Follicular dendritic reticulum cells were decreased in number in the neoplastic follicles compared with those in normal lymphoid follicles. Follicular lymphoma is rare in cattle. Histological features of the present cases are distinguishable from the adult form of bovine lymphoma and the calf form of lymphoma. PMID- 2258467 TI - Fever and changes in plasma zinc and iron concentrations in the goat. The effects of interferon inducers and recombinant IFN-alpha 2a. AB - Inflammation or invasion by pathogenic micro-organisms induces systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are fever, hypoferraemia and hypozincaemia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin-1 (Il-1), interferons (IFN-alpha) and tumour necrosis factor (TNF). The present report describes a comparative study in dwarf goats on recombinant human IFN-alpha 2a (0.5 x 10(5) IU per kg intravenously (i.v.) and 0.5 x 10(6) IU per kg intramuscularly (i.m.], Poly I:Poly C (an interferon inducer; 30 micrograms per kg i.v.), Newcastle disease virus La Sota strain (an interferon inducer; 0.5 ml per kg i.v.) and Escherichia coli endotoxin (an Il-1 and TNF inducer; 0.1 microgram per kg i.v.). The i.v. injection of recombinant IFN-alpha 2a caused characteristic monophasic febrile reactions, but no significant changes in plasma zinc and iron concentrations. The temperature responses were not due to endotoxin contamination because polymyxin B, which blocks endotoxin, had no inhibitory effect on the pyrogenicity of IFN-alpha 2a. In contrast, the IFN-alpha 2a-induced fever was completely prevented by flurbiprofen pretreatment (1 mg per kg i.v.). In contrast to the i.v. administration, i.m. injection of IFN-alpha 2a caused fever, hypoferraemia and hypozincaemia. Similar results were obtained after E. coli endotoxin, NCD La Sota strain and Poly I:Poly C injection. However, the shapes of the temperature curves and the changes in trace metal concentrations were markedly different. These data support the theory that fever and the changes in plasma zinc and iron concentrations are regulated by different mechanisms. PMID- 2258468 TI - Natural Dermatophilus congolensis infection in camels (Camelus dromedarius) from Kenya. AB - Natural Dermatophilus congolensis infection is found in many species of livestock and wild animals. It is, however, rarely described in camels and there are no details of bacterial isolation. In an investigation of both arid and semi-arid areas in Kenya, an outbreak of dermatophilosis was observed in camel calves being reared on a commercial farm in a semi-arid area. Histopathology and bacterial isolation were used to diagnose the diseases. The potential impact of the disease in camels is discussed. PMID- 2258469 TI - Hydrocortisone protects cycloheximide-challenged mice pretreated with Ehrlich ascites tumour cells or with cell-free Ehrlich ascites tumour fluid. AB - The invariably fatal outcome following cycloheximide challenge of mice pretreated 24 h earlier with either 1 x 10(7) washed Ehrlich ascites tumour cells i.v. or with 0.2 ml of cell-free Ehrlich ascites tumour fluid i.v. was prevented by hydrocortisone treatment. However, glucocorticosteroids failed to prevent the fatal outcome of cycloheximide challenge in mice bearing 5-day-old Ehrlich ascites tumours. The results are interpreted as indicating that there is a steroid demand which must be met to ensure survival of cycloheximide-challenged mice pretreated with tumour cells or with cell-free tumour ascites fluid and that an additional and essential requirement for uninterrupted protein synthesis exists in the case of mice with established ascites tumours and challenged with cycloheximide. PMID- 2258470 TI - Effect of intravenously administered tetrathiomolybdate on plasma copper concentrations of copper-loaded sheep. AB - Chronic copper toxicity was induced in 14 ewes in two groups by oral dosing with CuSO4. Copper dosing was stopped in sheep of groups 1 and 2 at the first rise of serum acid phosphatase activity and on the first day of haemolysis, respectively. Thiomolybdate was administered intravenously (i.v.) to sheep of group 2 at the rate of 100 mg on the first day of haemolysis and at 24-h intervals, with a maximum of 3 doses during haemolysis. Thiomolybdate was also given intravenously at a dose of 50 mg twice weekly for 11 weeks to four sheep of group 1 after the cessation of copper dosing (group 1B) and to five sheep of group 2 at the end of haemolysis. Plasma copper concentration was determined before and 24 h after each injection of 50 mg thiomolybdate and "elevations" of plasma copper concentration were seen after each injection of thiomolybdate. The differences between plasma copper concentrations observed before and after each thiomolybdate injection for doses 1 to 11 were significantly higher than those seen for doses 12 to 22. Following thiomolybdate administration, the copper content of the liver of sheep in groups 1B and 2 was reduced much more than in sheep of group 1A, in which copper dosing also ceased but which did not receive thiomolybdate. It was concluded that the high plasma copper response to thiomolybdate doses 1 to 11 was due to an influx of copper into the bloodstream from the heavily copper-loaded liver cells. The lower plasma copper response during the latter part of thiomolybdate administration was due to a gradual reduction in the amount of copper entering the bloodstream from the liver cells, as these cells became depleted of copper. Some of this copper may become part of the glomerular filtrate and be taken up by the cells of the proximal convoluted tubules of the kidney or may be excreted in the urine. PMID- 2258471 TI - Hippocampal neuronal necrosis in control Fischer 344 rats. AB - Brain tissue sections from control male and female Fischer 344 (F344) rats from ten National Toxicology Program (NTP) Bioassays were histomorphologically reviewed for non-neoplastic lesions of the hippocampus. Unilateral segmental hippocampal neuronal necrosis, which has not been reported in normal rats, was observed in 9 of 433 (2.1 per cent) males and 1 of 454 (0.2 per cent) females. Significant coexisting lesions were left-sided atrial and/or valvular thrombosis, metastatic mesothelioma, and large lymphocyte leukaemia. These data suggest that this naturally occurring lesion of predominantly aged male rats may result from an impairment of cerebral perfusion secondary to vascular obstruction by thrombotic emboli or leukaemic cells and haemolytic anaemia concomitant with large lymphocyte leukaemia, which commonly occurs in F344 rats. PMID- 2258472 TI - Morphology of equine allantochorion at the tip of the pregnant horn. AB - The morphology of the equine allantochorion at the tip of the pregnant horn was studied in the membranes of 14 mares. The findings in the allantochorion at the tip of the pregnant horn were of two types; one was growth retardation (hypoplastic villi, tunica adventitia of the vessels resembling embryonal connective tissue and the extended spaces of remnants of the extraembryonic coelom), the other was placental hypoxia or ischaemia (parakeratosis, stratified squamous metaplasia, necrosis of the trophoblasts, thickening of the basement membrane and fibrous hyperplasia of villous stroma). It seems likely that hypoplastic villi are caused by disordered formation of the microcotyledon accompanying the progression of pregnancy. PMID- 2258473 TI - Pathology of excessive iron storage in the Afghan pika (Ochotona rufescens rufescens). AB - Iron deposition in the tissues of 30 Afghan pikas (Ochotona rufescens rufescens) was examined histopathologically. In all cases, iron deposits were present in the liver and in two-thirds of cases, there was portal fibrosis with tissue injury. In animals, in general, tissue injury induced by iron overload is usually mild and only in a few exceptional species does hepatic haemochromatosis occur. Thus, Afghan pikas are a rare example of reaction to iron overloading. PMID- 2258474 TI - Pericapillary fibrin cuff: a histological sign of venous leg ulceration. AB - The incidence of pericapillary fibrin cuffs was investigated in 49 biopsies of venous leg ulcers and 67 biopsies of leg ulcers of non-venous etiology. Pericapillary fibrin cuffs were seen in 28 biopsies (57.1%) of venous leg ulcers, but only in 11 biopsies (16.4%) of non-venous leg ulcers. In the venous leg ulcers pericapillary fibrin cuffs occurred predominantly near the ulcer surface and around dilated capillaries. Dilation of the capillaries and inflammation probably contribute more to the pathogenesis of pericapillary fibrin cuffs than venous hypertension. PMID- 2258475 TI - Solitary sclerotic fibroma. AB - A 63-year-old Chinese man with a solitary sclerotic fibroma on the abdomen is described. Skin biopsy showed a well-demarcated dermal nodule composed of hypocellular, eosinophilic collagen bundles separated by prominent clefts. Retrospective electron microscopic study revealed wide collagen bundles containing tightly packed collagen fibrils, only 50 nm in diameter. There were no signs of Cowden's disease. To our knowledge, this is the first report of electron microscopic study of sclerotic fibroma. A brief review of the literature is included. PMID- 2258476 TI - An unusual cutaneous metastasis of a chondrosarcoma. AB - We report a case of cutaneous metastases from a scapular chondrosarcoma in a 85 year-old man. The metastatic skin lesion was noted nine years after resection of the primary tumor. Metastases to lung and soft tissues had occurred four years earlier. The patient also had a history of malignant melanoma. Although this case illustrates an unusual pattern of metastases, we conclude that the appearance of cutaneous lesions in a patient with a prior history of chondrosarcoma should alert the clinician to the possibility of a metastatic chondrosarcoma. PMID- 2258477 TI - Angioleiomyoma within a histiocytoma. AB - We report an angioleiomyoma developed within a cellular histiocytoma on the calf of a 77-year-old man. The lesion consisted of a spherical nodule with two well defined concentric areas. The outer circular area was a cellular histiocytoma and the inner central area consisted of an angioleiomyoma. Immunoperoxidase investigations for desmin demonstrated positivity in the angio-leiomyoma, whereas the histiocytoma remained negative. Serial sections of the lesion failed to demonstrate a connection between the angioleiomyoma and a normal vein which could have been trapped by the histiocytoma. The angioleiomyoma may have originated from a vessel in the histiocytoma. PMID- 2258478 TI - Abstract of papers presented at the 28th annual meeting of the American Society of Dermatopathology. Atlanta, November 28-30, 1990. PMID- 2258480 TI - Distribution of the lysosomal enzyme aryl sulfatase in murine mammary tissue through pregnancy, lactation, and involution. AB - Mammary tissue from 44 primiparous mice at various stages of pregnancy, lactation, and involution were stained for aryl sulfatase (lysosomal marker enzyme) activity and prepared for electron microscopy. Stereological techniques were used to determine the distribution of lysosomes per unit of cytoplasmic area in mammary epithelial cells. The number of primary lysosomes (containing only enzyme) was stable throughout the study, except for a temporary increase following parturition. Secondary lysosomes (containing substrate undergoing active digestion) designated as either telolysosomes or dense bodies were more frequent in mammary epithelial cells from animals in the late involution and early pregnancy stages than in lactating animals. However, telolysosomes did increase temporarily at the onset of lactation and casein micelles were identified within secondary lysosomes throughout the lactation stage. The frequencies for endoplasmic reticulum and Golgi apparatus containing aryl sulfatase reaction product were highest in secretory cells, when these structures were predominant. Shifts in lysosomal populations throughout the study suggests that lysosomes may have an active role within the mammary epithelial cells during differentiation and secretion as well as during involution. PMID- 2258479 TI - Effective control of microbial populations in polysulfone ultrafiltration membrane systems. AB - Sanitizers currently used in the food industry are not efficient in destroying bacterial populations in polysulfone UF membrane systems. A new sanitizer composition that releases chlorous acid and chlorine dioxide from sodium chlorite at pH 2.7 was evaluated. Polysulfone UF membranes were soiled for 2.5 h by circulating and concentrating Cheddar cheese whey and skim milk. A cleaning regimen was established whereby acid and caustic cleaning solutions were circulated to clean the UF membrane system. Restoring permeate flux to initial values did not indicate that the system was effectively cleaned. The UF system was sanitized by recycling sanitizer solutions. Stainless steel and membrane surfaces were examined by swabbing to determine bacterial populations and sections of membranes were removed for examination using a scanning electron microscope. The new sanitizer appeared to control microbial populations effectively in UF membrane systems. PMID- 2258481 TI - Trace elements in milk of guinea pigs during a 20-day lactation. AB - This study was designed to determine patterns of change in milk trace elements over a complete lactation. Guinea pigs were selected because of ease of milking and short lactation duration. Common short-hair albino guinea pigs were milked using a milking apparatus for 4 to 6 h every other day following isolation from their offspring. Forty-eight samples of 4 ml each were analyzed for trace minerals using inductively coupled plasma spectroscopy. Observations represented 14 d scattered over 20 d of lactation. Eight elements with sufficiently high quantities to measure in milk were zinc (4.18 ppm), strontium (1.12), aluminum (.81), boron (.79), iron (.71), copper (.56), barium (.23), and manganese (.019). Regression analyses were used on rectilinear, quadratic, exponential and cubic models. Quadratic functions fit the data best in six elements, whereas in manganese the best model was the rectilinear. Indices of determination (R2) relating to day of lactation varied from R2 = .18 in boron to a high of .62 in strontium. For six elements, concentrations increased as milk volume decreased. The exception was zinc, which decreased in the latter half of lactation. PMID- 2258482 TI - Effect of plane of nutrition on growth and mammary gland development in Holstein heifers. AB - Forty-one Holstein and 6 Holstein crossbred heifers, 6 to 8 mo of age, were used to determine the effect of plane of nutrition on growth and mammogenesis prior to and during puberty. Animals were fed to gain 611 g (low), 737 g (medium), and 903 g (high) by a diet of cracked corn and chopped alfalfa-grass hay. Mammary biopsies were carried out in vivo to determine if they provide acceptable information on mammary composition (based upon morphometric evaluation) in comparison with dissected glands. Results indicated that NRC (1978) recommendations for average daily gain of Holstein heifers between 6 and 16 mo may be too generous. At puberty (first estrus), age and wither height decreased linearly with increasing plane of nutrition, whereas body weight and hip height were not affected by plane of nutrition. Five heifers were slaughtered at the beginning and 18 at the conclusion of the trial. Increasing plane of nutrition resulted in fatter mammary glands with decreased concentration of DNA, whereas total mammary DNA did not differ among treatment groups. In this study, morphometric evaluation of mammary tissue obtained through biopsies did not yield useful information in comparison to chemical analysis of dissected glands. PMID- 2258483 TI - Effects of excess degradable protein on postpartum reproduction and energy balance in dairy cattle. AB - The objectives of this study were to observe endocrine and reproductive responses of cows and heifers fed two diets (16 and 19% CP), which met undegradable protein requirements but differed in rumen degradable protein. Cows (n = 33) and heifers (n = 32) were randomly assigned within parity to diets at calving and remained on diets for 20 d after first breeding. Energy balance was determined twice weekly through the first luteal phase. Blood and milk samples were taken three times per week. Diet did not affect average daily energy balance, days to negative energy balance nadir, days to first ovulation, days to first service, or plasma glucose concentrations. First service conception rate was lower (31% vs. 48%) and plasma urea higher in animals fed the high protein diet. Days to energy balance nadir was correlated with days (r = .75) to first ovulation. Luteinizing hormone pulse frequency increased and pulse amplitude decreased in frequent samples (12-min intervals for 8 h) collected at 14 d postpartum versus sampling after the energy balance nadir. These data suggest that energy balance status plays an important role in determining the postpartum return of cyclic ovarian activity. Feeding excess CP as rumen degradable protein elevated plasma urea concentrations and decreased first service conception rate. PMID- 2258484 TI - Effect of nordihydroguaiaretic acid on luteal phase length and oxytocin-induced release of prostaglandin F2 alpha in heifers. AB - Two experiments were conducted to determine if intrauterine infusion of nordihydroguaiaretic acid, a lipoxygenase pathway inhibitor, would delay luteolysis (Experiment 1) and inhibit oxytocin-induced release of prostaglandin F2 alpha (as measured by the stable prostaglandin F2 alpha metabolite, 15-keto 13,14-dihydroprostaglandin F2 alpha) in plasma on d 16 (d 0 = estrus) of the estrous cycle (Experiment 2). Nordihydroguaiaretic acid (20 mg) or saline was infused twice daily into the uterus on d 14 to 23 (Experiment 1) or d 14 to 20 (Experiment 2) postestrus, respectively. In Experiment 1 and 2, mean concentration of progesterone was higher and luteolysis was delayed in nordihydroguaiaretic acid-infused heifers compared with saline-infused heifers. In Experiment 2, saline or oxytocin (100 IU, i.v.) was injected into each heifer on d 16 postestrus to stimulate the release of prostaglandin F2 alpha from the uterus. Mean concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha increased within 1.5 h postinjection in heifers infused with saline, whereas concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha in nordihydroguaiaretic acid-infused heifers did not increase within the same time period. Thus, nordihydroguaiaretic acid may inhibit both the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism and therefore delay luteolysis. PMID- 2258485 TI - Effect of diseases, production, and season on traumatic reticuloperitonitis and ruminal acidosis in dairy cattle. AB - Logistic regression was used to investigate the effects of host characteristics, production, and 23 veterinary diagnoses on the risks of two reticuloruminal disorders, ruminal acidosis and traumatic reticuloperitonitis among 61,124 Finnish Ayrshire cows. Lactational incidence risks were .3% for ruminal acidosis and .6% for traumatic reticuloperitonitis. The relative risk of ruminal acidosis was not related to parity, whereas the risk of traumatic reticuloperitonitis decreased with increasing parity. The risk of traumatic reticuloperitonitis was not related to milk yield of individual affected cows in their current or previous lactation (305-d, 4% FCM), whereas the risk of ruminal acidosis increased with current milk yield. Ketosis, early metritis, nonparturient paresis, and acute and chronic mastitis were risk factors for both reticuloruminal disorders. Parturient paresis was a risk factor for ruminal acidosis. Foot and leg problems were risk factors for traumatic reticuloperitonitis. Herd milk yield in the current or previous lactations was not a risk factor for either disorder nor were the two disorders risk factors for each other. Ruminal acidosis, but not traumatic reticuloperitonitis, had significant seasonal variation with the risk being least in summer. The low risk of ruminal acidosis in summer was not due to seasonality of calving. PMID- 2258486 TI - Comparison of semen quality in young and mature Holstein bulls measured by light microscopy and flow cytometry. AB - Random samples of cryopreserved, milk-extended semen, collected from 20 Holstein bulls at about 14 mo of age (young) and again at about 4 yr of age (mature), were evaluated at thawing and during 3-h incubation to compare semen quality of young versus mature bulls. Evaluation by differential interference contrast microscopy showed greater proportions of cytoplasmic droplets in semen from young versus mature bulls. Mature bulls exhibited greater proportions of intact acrosomes in freshly thawed semen than did young bulls. Evaluation of sperm chromatin structure by flow cytometry after staining with acridine orange showed lower values for mature versus young bulls, indicating resistance of DNA in nuclear chromatin to acid denaturation increased with age. Correlations between ages for most sperm morphology, acrosome integrity, and flow cytometry variables were high and positive. Nonreturn rate for young bulls was positively related to morphologically normal sperm and acrosomal integrity and negatively related to flow cytometry traits. Results suggest semen quality of young bulls was related to subsequent quality as mature bulls. With flow cytometry, differences were detected between semen samples that were not evident with light microscopy. PMID- 2258487 TI - Relationships among vitamin E, selenium, and bovine blood neutrophils. AB - Effects of vitamin E and selenium supplementation on in vitro phagocytosis and intracellular kill of bacteria by bovine neutrophils were investigated. Diets were not supplemented with vitamin E and selenium during the dry period and first 21 d of lactation. Cows were then assigned to one of four treatment diets for 30 d. Treatment diets were either unsupplemented or supplemented with vitamin E, selenium, or both vitamin E and selenium, in a 2 x 2 factorial arrangement. Peripheral blood neutrophils were isolated from each cow on lactation d 51. Vitamin E supplementation of diets increased intracellular kill of Staphylococcus aureus and Escherichia coli by neutrophils. Intracellular kill of S. aureus was greater in neutrophils isolated from selenium supplemented cows than in neutrophils from cows without supplemental selenium. Intracellular kill of E. coli did not differ between neutrophils from selenium supplemented and selenium unsupplemented cows. Ability of neutrophils to phagocytize either S. aureus or E. coli was independent of vitamin E and selenium. PMID- 2258488 TI - Somatotropin treatment for a second consecutive lactation. AB - Twenty-five Holstein cows were used to examine effects of recombinant bST administration for a second successive lactation on milk yield and composition, BW change, body condition, and health. Treatments were 0 (physiological saline), 10.3, 20.6, and 33 mg bST/d (8, 8, 7, and 3 cows per treatment, respectively). Saline and bST were given daily as subcutaneous injections beginning 4 to 5 wk postpartum and continuing for 38 wk. Somatotropin increased 3.5% FCM yield linearly from 8 to 36% over controls (control FCM was 30.1 kg/d). Milk composition was not affected by bST except that milk from cows given the 10.3-mg dosage had slightly higher Ca and P contents than did milk from cows receiving 0 or 20.6 mg. Cows receiving bST were 9 to 30% more efficient than controls in converting feed to milk. Body weight gain was unaffected by treatment. Average condition score was unchanged for control cows during the first 84 d following initiation of treatment, but declined in cows given bST. Thereafter, condition score increased in a similar manner for all groups. No treatment-related patterns were found in incidence of mastitis, feet and leg problems, ketosis, or milk fever. Blood hormone, chemistry, and hematology revealed no effects of bST treatment other than to raise plasma bST concentrations. Under conditions of this experiment, use of bST during a second consecutive lactation did not change the normal physiology or productive capacity of lactating cows. PMID- 2258489 TI - Sixty-day infusions of somatotropin-releasing factor stimulate milk production in dairy cows. AB - Twenty-four Holstein cows were infused intravenously with sterile water (placebo) or 1,3, or 12 mg of recombinant bovine somatotropin-releasing factor 1-45 homoserine lactone/d for 60 d. Relative to placebo (22.8 kg/d), 3 and 12 mg of somatotropin-releasing factor increased yield of milk to 28.8 and 33.3 kg/d during infusion. At 1 mg of somatotropin-releasing factor, milk averaged 27.5 kg/d during infusion but was increased above placebo only through 39 d. After infusion of 12 mg somatotropin-releasing factor ended, milk (26.4 kg/d) remained above placebo amounts (20.6 kg/d) for 15 d. Three and 12 mg of somatotropin releasing factor increased serum somatotropin from .7 (placebo) to 8.2 and 10.3 ng/ml when averaged across 1, 30, and 59 d, whereas 1 mg increased somatotropin to 5.8 ng/ml after 1 d but had no effect at 30 or 59 d. Within 17 h of cessation of somatotropin-releasing factor infusion, serum concentrations of somatotropin were similar across all groups. On d 59, 3 and 12 mg infusions increased insulin like growth factor I from 115.8 (placebo) to 204.7 and 261.4 ng/ml of serum. We conclude that somatotropin-releasing factor increased serum concentrations of somatotropin and milk yield in a dose-dependent manner for at least 60 d. Also galactopoietic effects of somatotropin-releasing factor persisted for 15 d independent of increased concentrations of somatotropin in serum following withdrawal of somatotropin-releasing factor. PMID- 2258490 TI - Effect of energy level and feeding frequency on site of digestion and postruminal nutrient flows in steers. AB - Four cannulated (rumen, proximal duodenum, terminal ileum) Simmental steers were fed ground corn and corn silage (low forage) or alfalfa hay and corn silage (high forage) diets twice or 12 times daily to examine effects of energy level and feeding frequency on nutrient digestion. Site of organic matter digestion was shifted from the rumen to the small intestine, and total tract organic matter digestion was increased when steers were fed the low forage diet. Although intakes and flows at all sites within the tract of NDF and ADF were greater when the high forage diet was fed, digestion of these components (percentage total tract digestion) within respective sites was unaffected by energy level. Nonbacterial N flows at the duodenum increased when steers were fed the low forage diet and when fed 12 times daily. Total amino acid flows at the duodenum tended to be increased when steers were fed the low forage diet. Results suggest that dietary energy level can impact on site of nutrient digestion and supply of nutrients at different sites within the digestive tract. However, feeding frequency had minimal effect on site or extent of nutrient digestion. The lack of interaction between energy level and feeding frequency in this experiment may be related to the level of DM intake and nature of the diets fed. PMID- 2258491 TI - Composition of ruminal bacteria harvested from steers as influenced by dietary energy level, feeding frequency, and isolation techniques. AB - The effects of isolation techniques and time of sampling on composition of ruminal bacteria were examined in four steers fed two energy levels (2.24 or 2.92 Mcal metabolizable energy/kg DM) at two feeding frequencies. Diets were alfalfa hay and corn silage or ground corn/corn silage and were fed twice or 12 times daily. Whole ruminal contents were collected at four time intervals over a 4-d period. Fluid- and particle-associated bacteria were isolated. Energy level, feeding frequency, and preisolation freezing had little effect on composition of bacteria. Sampling time did not affect composition of bacteria harvested from steers fed frequently but had linear and quadratic effects on concentrations of cell components of bacteria harvested from steers fed twice daily. Differences were observed in the composition of bacteria harvested from the fluid phase compared with particle-associated or mixed populations of ruminal bacteria. These differences translated into different estimates of bacterial N supplied to the small intestine depending on N:purine ratio used. Composition of bacteria may be affected by fraction of contents sample and by time of sampling for animals fed infrequently. Freezing of samples before isolation of mixed bacteria does not appear to affect composition or estimates of bacterial N flows to the small intestine. PMID- 2258492 TI - Lipid compositional changes in calves fed excess iodine. AB - Calves were fed milk replacer containing .57, 10, or 200 ppm iodine (from ethylenediaminedihydriodide) to determine the effects of excess dietary iodine on composition of lipids in blood plasma, liver, and heart. High iodine intakes had no effect on plasma total lipids or lipid classes, but caused lipid class concentration changes in liver and heart. Both 10 and 200 ppm iodine increased concentration of liver phosphatidylethanolamine and heart phosphatidylcholine, cholesterol, and total lipids, and the 200 ppm intake also increased concentration of liver phosphatidylcholine, total lipids, and heart phosphatidylethanolamine. Both iodine treatments tended to increase all the other minor lipid classes in liver and heart as well. Both 10 and 200 ppm iodine treatments increased some of the n-3 polyunsaturated fatty acids in the major phospholipids of plasma, liver, and heart. For the preruminant calf, liver and heart may be more useful than blood plasma for indicating excess iodine effects on lipid metabolism. PMID- 2258493 TI - Transformation of multitrait to unitrait mixed model analysis of data with multiple random effects. AB - An algorithm for transforming a multitrait into a unitrait analysis was presented for a mixed model that has equal design matrices for t traits and contains more than one random classification. The class of models was restricted to those in which the covariance matrices for all random effects including the residual can be diagonalized simultaneously. A variation of this assumption was called the common principal component by Flury. As a result of the transformation, setting up and solving the laborious t trait mixed model equations becomes a simple matter of setting up and solving the unitrait mixed model equations separately for each of the t transformed traits. The present procedure would not only simplify computer programming but more importantly it would drastically reduce central processing unit time and computer space requirements. A numerical example was given to illustrate this procedure of indirect multitrait analysis in comparison with direct multitrait analysis. PMID- 2258494 TI - Association of genetic defects with yield and type traits: the weaver locus effect on yield. AB - The association of recessive genetic disorders with yield and type traits was investigated. The frequency of a defective gene could be increased by selection if it is positively associated with selected traits, despite efforts to reduce it. Genetic defects considered were weaver in Brown Swiss and rectovaginal constriction and limber leg in Jerseys. Data sets for linkage analysis consisted of 245 sons of 9 carrier sires, 1036 sons of 16 carrier sires, and 557 sons of 10 carrier sires, respectively. Weaver carrier sons had higher producing daughters than noncarrier sons within all 9 sire families. Weaver carrier cows have an advantage of 673.6 kg milk and 26.0 kg fat and a disadvantage in rear legs score, indicating that the condition may not be completely recessive. Carriers of the other defect genes have no advantage for milk production, are scored lower for pelvic angle, and limber leg carriers have more desirable udders. Estimates of defect gene frequencies in 264,000 Jersey cows show a decrease over time for rectovaginal constriction and limber leg; in 97,723 Brown Swiss cows, frequency of the weaver gene increased over time. Gene frequencies in daughters of the youngest sires were 5.48, 2.13, and 8.89%, respectively. Consistently higher yield evaluations of weaver carrier sons within each sire family, large advantage in production of weaver carrier cows, and increasing gene frequency over time indicate that a chromosome segment with major effect on yield is tightly linked to weaver in Brown Swiss. PMID- 2258495 TI - Rectovaginal constriction in Jersey cattle: genetics and breed dynamics. AB - Data from farmer-owned herds and from experimental matings supported monofactorial recessive inheritance of rectovaginal constriction in US Jersey cattle. Kempthorne's population genetics model of a recessive trait involving only male selection was extended to include mutation and converted to selection of females only. Computer analyses with that model estimate slow decline in the frequency of the gene for rectovaginal constriction. Practical dynamics of the disorder in a breed registering 50,000 females and 2,000 males annually are given for current conditions and after 500 generations of selection. PMID- 2258496 TI - Power of daughter and granddaughter designs for determining linkage between marker loci and quantitative trait loci in dairy cattle. AB - There is considerable interest in bovine DNA-level polymorphic marker loci as a means of mapping quantitative trait loci (QTL) of economic importance in cattle. Progeny of a sire heterozygous for both a marker locus and a linked QTL, which inherit different alleles for the marker, will have different trait means. Based on this, power to detect QTL, as a function of QTL effect, heritability of the trait, and number of animals tested was determined for 1) daughter design, marker genotype and quantitative trait values assessed on daughters of sires heterozygous for the markers; and 2) granddaughter design, a newly devised alternative design in which marker genotype is determined on sons of heterozygous sires and quantitative trait value measured on daughters of the sons. For equal numbers of assays, power increased with the number of daughters per sire (design 1) and sons per grandsire (design 2). For equal power and heritability less than or equal to .2, design 2 required half as many marker assays as design 1, e.g., with heritability of .2, QTL effect of .2 SD units, and type 1 error of .01, power was .70 if 400 daughters of each of 10 sires were assayed for the markers and .95 if markers were assayed on 100 sons of each of 20 sires with 50 granddaughters per son. PMID- 2258497 TI - Association of class I bovine lymphocyte antigen complex alleles with health and production traits in dairy cattle. AB - Ninety-eight Holstein cows from the I-O-State breeding research herd were serologically typed for class I bovine lymphocyte antigens. After exclusion of animals carrying alleles that occurred at frequencies lower than 4%, records from 82 cows that had 161 lactations remained for analysis of major histocompatibility complex allelic effects. A gene substitution model was used to evaluate the additive effects of nine alleles (frequencies of 4 to 20%) at the bovine lymphocyte antigen complex A locus on general health, udder health, and production traits. Allele w14(w8) was associated with decreased quarter milk sample California Mastitis Test scores, composite milk sample California Mastitis Test and Wisconsin Mastitis Test scores, decreased total health costs, and with increased milk yield, fat yield, fat percentage, and income over feed costs. Allele w11 was associated with decreased clinical mastitis, discarded milk, and udder health costs but was also associated with decreased fat yield, fat percentage, and income over feed costs. Allele w31(w30) was associated with decreased fat percentage. These relationships suggest that alleles at the bovine lymphocyte antigen complex A locus may serve as markers for health and production traits. Thus, the potential may exist for enhancement of disease resistance or production in cattle via marker-assisted selection and genetic manipulation techniques using class I genes of the bovine major histocompatibility complex. PMID- 2258498 TI - Calving disorders of primiparous Holsteins from designed selection studies. AB - Primiparous Holsteins from designed studies were evaluated for edema, dystocia, and retained placenta. Genetic studies were 1) selection for large body size versus small body size, and 2) milk yield selection versus control (no selection). The large body size group was mated to sires with extreme estimates of transmitting ability for tall height and deep and wide bodies. Small body size group was mated to extreme sires for transmitting short height and shallow, narrow bodies. Large and small cows significantly differed only for edema, and small cows had scores suggesting more severe udder edema than large cows. Milk selection group was mated to the four highest sires for PTA milk each year, whereas a control group was mated to 20 randomly selected AI sires that were breed average for PTA milk in 1964. Selection groups for milk yield did not differ significantly for any of the calving disorders. PMID- 2258499 TI - Genotype by environment interaction and genetic correlations among parities for somatic cell count and milk yield. AB - Lactation measures of somatic cell concentration and total SCC production were developed. Data were separated into three parity groups. Within parity, five data sets were created: four subsets by herd-year average SCC, and one with all records. Records on lactation SCC, total SCC production, and 305-d milk were analyzed by a sire model separately in each subset within parity. Variance components estimates were by REML. For SCC and total SCC production, heritability estimates averaged .12 and were lowest in the highest level of herd-year average SCC. Estimates of genetic correlation between SCC and total SCC production were over .95; between SCC and 305-d milk were around .25 in first and -.15 in later parities; between total SCC and 305-d milk were around .50 in first and .15 in later parities. Product-moment correlations between sire effects in different levels of herd-year average SCC were obtained. Ratios of product-moment correlations to their expected value were above .80 for all traits in all parities. High ratios indicated little genotype by environment interaction. A sire by herd interaction was fitted in the model and accounted for less than 2% of total phenotypic variance for SCC and total SCC production, and 4% for 305-d milk. Estimates of genetic correlation of first with later parities were .71 to .86 for all traits. Between second and third parity genetic correlation estimates were around unity for all traits. Records from all parities should be used for sire evaluation. PMID- 2258500 TI - Approaching adolescence. PMID- 2258501 TI - Reaching more children with needed dental services. AB - If we are to reach more children with needed dental services, needed financial support is essential, as well as an appreciation of the attitudes and motivation of children and their parents and guardians regarding their dental health and needed services. As children's perceptions can be modified, efforts to provide these services can be enhanced. PMID- 2258502 TI - Occurrence of primary incisor traumatism in Brazilian children: a house-by-house survey. AB - This paper presents the results of a house-by-house survey to learn the occurrence of dental injury to the primary teeth in Brazilian children from ten to seventy-two months of age. The study sample comprised 576 children, 295 boys and 281 girls living on sixty-six streets selected in an urban area (Bauru) in the state of Sao Paul, Brazil. There were 174 children (30.2 percent) with positive reports of injuries to the primary teeth. The results show the need of an educational program in order to prevent the occurrence of dental trauma. PMID- 2258504 TI - In vitro assessment of the microleakage around preventive resin (laminate) restorations. AB - The purpose of this study was to evaluate in vitro, the microleakage of laminate restorations using two resin systems and the influence of etching and curing regimen on the leakage. A total of 135 extracted, human third molars with similar occlusal dimensions were chosen. Cavities were prepared and the teeth were then separated into nine groups of fifteen teeth each. The incidence of microleakage in this study varied between no leakage and 46.7 percent. Leakage of preventive resin restorations was reported to occur in 16.7 percent to 25 percent of cases. The fact that the variables tested in this study had no significant effect on the microleakage would suggest that the leakage is dependent on that of the fissure sealant. The group restored with a fissure sealant containing releasable fluoride and an adhesion promoter performed well in this study. PMID- 2258503 TI - Occlusal hidden caries: a bacteriological profile. AB - Eleven teeth from nine patients with occlusal caries lesions beneath an apparently intact enamel surface were treated. Two dentine samples, one from the dentinoenamel junction (Sample A) and one just before all the caries appeared to be removed clinically (Sample B), were taken under aseptic conditions and examined for bacteria. In all cases, the A samples and in ten cases the B samples contained mutans streptococci, lactobacilli or both, while in ten cases the dentine after opening was soft with a light color. This suggests that we are dealing with active caries lesions, which should be treated as such. The salivary data of the patients group were compared with the salivary data of the control group. Although the buffer capacity of the groups were not significantly different (chi-square), further analysis revealed that a significant relationship could be found between the group and the buffer capacity (Kendall's Tau C). While the other salivary components (numbers of mutants streptococci per ml saliva and the secretion rate) showed no significant differences. Unfortunately these occlusal caries lesions are not detected with the present criteria used in epidemiological surveys. PMID- 2258505 TI - Permanent molar impactions and an odontogenic keratocyst: report of case. AB - A case of permanent molar impactions involving maxillary and mandibular second and third molars is reported. An odontogenic keratocyst was present in conjunction with root resorption of adjacent teeth. Treatment involved surgical removal of the impacted teeth and enucleation of the cystic lesion. PMID- 2258506 TI - Management of cervical root perforation: report of a case. AB - The case reported here demonstrates, in the planning and treatment of this patient, a good example of teamwork among different dental specialities. The clinical examination of a healthy, sixteen-year- old Swedish boy produced the diagnoses of osteitis periapicalis resorptiva chronica and root perforation, after unsuccessful treatment by the school dentist who had referred the patient. Orthodontic extrusion was preferred to a surgical approach. The prosthetic treatment was completed immediately after finishing the endodontic procedures. PMID- 2258507 TI - Cyromazine resistance in the house fly (Diptera: Muscidae): genetics and cross resistance to diflubenzuron. AB - Larvae of a house fly, Musca domestica L., strain collected in a chicken house near Pittsburg, Tex, after a control failure with the poultry feedthrough insecticide cyromazine showed 6.5-fold resistance to cyromazine and 10-fold resistance to diflubenzuron. Adults of the strain showed high levels of resistance to carbaryl, DDT, and diazinon; moderate resistance to cypermethrin and permethrin; and low resistance to dieldrin. In contrast, no resistance to cyromazine was observed in eight laboratory house fly strains with resistance to four groups of conventional insecticides. When the genetics of cyromazine resistance was investigated in crosses to susceptible strains with visible mutant markers, results indicated cyromazine resistance was incompletely dominant over susceptibility and the resistance gene was on chromosome V. The same or a closely linked gene conferred resistance to diflubenzuron. A strain containing only chromosome V from the original resistant strain was resistant to cyromazine and diflubenzuron, but not to other insecticides except for low level resistance to DDT and carbaryl. Resistance to the latter insecticides appeared to be due to a linked, but distinct, gene. Therefore, resistance to cyromazine and probably diflubenzuron appears to be genetically distinct from other types of insecticide resistance. PMID- 2258508 TI - Insecticide toxicity, synergism and resistance in the German cockroach (Dictyoptera: Blattellidae) AB - The toxicity of synergism of and resistance to insecticides in four strains of German cockroach, Blattella germanica (L.), were investigated. Toxicity of nine insecticides by topical application to the susceptible strain varied greater than 2,000-fold, with deltamethrin (LD50 = 0.004 micrograms per cockroach) and malathion (LD50 = 8.4 micrograms per cockroach) being the most and least toxic, respectively. Resistance to pyrethrins (9.5-fold) in the Kenly strain was unaffected by the synergists piperonyl butoxide (PBO) or S,S,S tributylphosphorotrithioate (DEF), suggesting that the metabolism is not involved in this case. Malathion resistance in the Rutgers strain was suppressible with PBO, implicating oxidative metabolism as a resistance mechanism. The Ectiban-R strain was resistant to all the pyrethroids tested, and cypermethrin resistance was not suppressible with PBO or DEF. These findings support results of previous studies that indicated this train has a kdr-like mechanism. Bendiocarb resistance in both the Kenly and Rutgers strains was partially suppressed by either PBO or DEF, suggesting that oxidative and hydrolytic metabolism are involved in the resistance. Trends between the effects of the synergists on the susceptible versus resistant strains are discussed. PMID- 2258509 TI - Esterase B1 activity variation within and among insecticide resistant, susceptible and heterozygous strains of Culex quinquefasciatus (Diptera: Culicidae). AB - Amplification of the esterase B1 gene of Culex quinquefasciatus Say results in high titers of an esterase enzyme that confers resistance to organophosphate insecticides. Esterase activity of individuals was measured in samples from an organophosphate resistant strain (Tem-R), a susceptible strain (S-Lb), and their reciprocal F1 progeny. Within-strain variation, as measured by coefficients of variation, was fairly consistent between sexes within strains and among strains (average, 12%). On average, individuals from the Tem-R strain had about 120 times the esterase activity of individuals from the S-Lab strain. The mean esterase activities of the F1 strains were significantly higher than the average of the Tem-R and S-Lab strain mean esterase activities, suggesting enhanced expression of the amplified esterase B1 genes in F1 individuals. Reciprocal F1 strains did not differ significantly in esterase activity or resistance, indicating that maternal effects do not influence either of these measures in these strains. The levels of esterase activity of the strains are discussed in relation to their resistance. PMID- 2258510 TI - Differential survival of male and female partially resistant horn flies (Diptera: Muscidae) on steers treated with permethrin. AB - Males and females from a heterozygous, resistant strain (SR) of the horn fly, Haematobia irritans (L.), were tested for survival until reproductive maturity on steers with ear tags in outdoor, screened enclosures and on steers sprayed on the neck in an indoor isolation room. After 6 d, female SR flies on outdoor steers with one tag had 10 times greater survival than males; almost no SR flies on steers with two ear tags survived. Survival of male and female SR flies on steers sprayed on the neck was reduced during the first 24 h, but not thereafter. Lower survival of males compared with females on treated steers reflected differential survival of the sexes during exposure to treated cloths in a laboratory bioassay. Hair samples from neck, back, rump, and lower legs of steers with ear tags in outdoor pens were tested for toxicity to the SR flies. These bioassays indicated high localization of insecticide on the neck of steers with ear tags. PMID- 2258511 TI - Linkage, expression, and distribution of the pyrethroid resistance gene in the horn fly (Diptera: Muscidae). AB - A sex-linked gene for pyrethroid resistance in the horn fly, Haematobia irritans (L.), showed complete linkage to the male-determining gene in a laboratory colony that had been inbred for 10 generations. Within susceptible, heterozygous, and resistant populations, the level of resistance that was expressed was greater for females than for males. The increase in level of resistance conferred by the gene was similar for females and males. Preliminary synergism and allelism tests supported our supposition that the same gene was responsible for resistance in California, Florida, and Texas populations. PMID- 2258512 TI - Sprayable self-encapsulating starch formulations for Bacillus thuringiensis. AB - Under glasshouse conditions, various cornstarches and adjuvants were examined as encapsulating agents in sprayable formulations for Bacillus thuringiensis subsp. kurstaki Berliner. When these materials were suspended in water and tested for physical factors such as viscosity, clumping, and retention on plant surfaces, a range of responses was observed. All formulations tested had acceptable viscosity, but some formulations clumped. When applied to cotton leaves, certain formulations remained less than 4 d, whereas others remained greater than 2 wk. One of these formulations containing equal parts of Mira-sperse (a commercially available pregelatinized cornstarch) and sucrose (6% total solids) was selected for testing persistence of B. thuringiensis insecticidal activity against Ostrinia nubilalis Hubner neonate larvae. When encapsulating agents were present, insecticidal activity decreased over a 2-wk period significantly more slowly than when encapsulating agents were absent. This indicates an enhanced persistence of B. thuringiensis under glasshouse conditions. Implications of a sprayable self encapsulating formulation for B. thuringiensis are discussed. PMID- 2258513 TI - Residual effectiveness of insecticides for control of German cockroaches (Dictyoptera: Blattellidae) in food-handling establishments. AB - Residual effectiveness of insecticides was compared for two treatment methods at various sites within two commercial kitchens. For all sites and insecticides, German cockroach, Blattella germanica (L.), mortality was greatest for treatments of cracks and crevices than for treatments of exposed surfaces. Mortality at the dishwashing site was lower than at all other sites. We attributed reduced mortality at the dishwashing site to a higher vapor pressure deficit. Mortality and the amount of insecticide residue recovered from treated surfaces were closely correlated. These data demonstrate that careful placement of residual insecticide treatments will influence their effective longevity. PMID- 2258514 TI - A detector dog for screwworms (Diptera: Calliphoridae). AB - A male German wirehaired pointer, Canis familiaris L., was trained to search for and locate screwworm, Cochliomyia hominivorax (Coquerel); pupae; and animals infested with screwworms. The command, "find it" led to the detection of a screwworm-infested animal and the command "search" led to the detection of screwworm pupae. After approximately 5 mo of training, the dog could detect screwworm-infested animals. After 3 mo more of training, the dog could detect screwworm pupae. Through 7 August 1989, the dog had a success rate of 100% (265 tests) with training dummies and 94.7% (18 successes for 19 tests) with screwworm infested animals, for an overall success rate of 99.7% (285 successes for 286 tests). Use of detector dogs at quarantine stations could result in increased efficiency, economic savings, and decreased possibility of reintroduction of screwworms into eradicated areas. PMID- 2258515 TI - Susceptibility of insecticide-susceptible and wild house flies (Diptera: Muscidae) to abamectin on whitewashed and unpainted wood. AB - Unpainted plywood panels treated with 0.1% abamectin (avermectin B1) provided greater than 90% control of house flies, Musca domestica L., susceptible to insecticides for 4 wk and greater than 70% control for 7 wk compared with 46-92% control observed with permethrin at the same time and rate of application. Efficacy of abamectin on whitewashed panels was similar to that observed on unpainted panels, whereas permethrin was ineffective on whitewashed panels at all rates tested (range, 0.001-0.1%) at all intervals after treatment. Bioassays of newly colonized house flies resistant to permethrin indicated that wild populations may be cross-resistant to abamectin. PMID- 2258516 TI - Police are best at community care of mentally ill people in England. PMID- 2258517 TI - The use of the Ethnograph program to identify the perceptions of nursing staff following the introduction of primary nursing in an acute medical ward for elderly people. AB - Interviews with a small group of nurses working in a primary nursing ward were content analysed using the Ethnograph computer program. In response to some very general questions about their views of primary nursing, the respondents talked at some length about their improved knowledge of patients, about better communication, about their relationships with patients and relatives and about personal responsibility. They did not talk spontaneously about controlling their own practice, decision-making, autonomy or accountability. Such terms did not form part of their vocabulary in describing their work though these issues were raised obliquely in the conversations. The value of the change in the way of organizing the delivery of nursing care was seen more in terms of its potential for developing therapeutic relationships rather than in terms of personal professional development. Increased knowledge of and responsibility for specific patients coupled with the greater continuity of care they were able to provide, gave them greater job satisfaction than they had previously experienced. PMID- 2258518 TI - Evaluating the efficacy of the infection control liaison nurse in the hospital. AB - The infection control liaison nurse (ICLN) is a nurse in the ward, appointed to participate in education for infection control, and to liaise between the ward and the infection control nurse (ICN). The efficacy of ICLNs was evaluated when a guideline on urinary catheter care was introduced in a 1000-bed hospital in Hong Kong. The 27 public wards were divided randomly into a test (24 wards) and control group (three wards), and ICLNs were appointed in the test group by the nursing administration. For education, the ICN conducted in-service lectures for both groups, while in the test group, the ICLNs also conducted tutorials for all ward nurses. Before and after the education programme, prevalence surveys were conducted to detect incorrect practices on urinary catheter care. Three practices were evaluated: the securing of catheters, presence of kinking and the use of urinary bags with a drainage spigot. Before education, the percentage of incorrect practices in the test groups was 63%, which was comparable to the 68% of the control group (P = 0.40, chi 2 = 0.71). After education, the percentage of incorrect practices in the test group (36%) was significantly lower than the 48% in the control group (P less than 0.05, chi 2 = 4.25). This indicates that ICLNs can indeed enhance the education programme for infection control. PMID- 2258519 TI - Self-efficacy and activity level following cardiac surgery. AB - Self-efficacy expectations were measured in 149 recovering cardiac surgery patients to determine whether in-patient education and telephone monitoring during convalescence enhanced perceptions of cardiac efficacy and reported activity. Significant differences were found for experimental patients in self efficacy expectations for walking between 4 and 8 weeks (P = 0.02) and between 8 and 24 weeks (P = 0.05) following surgery. Experimental patients also reported higher levels of general activity at 4 weeks (P = 0.05) and 8 weeks (P = 0.02) as well as more walking and lifting at 8 weeks (P = 0.01 and P = 0.0008, respectively). By 12 weeks, treatment differences were no longer significant except for continued higher general activity levels (P = 0.03) for experimental patients. Self-efficacy expectations, summed for all physical activities, at at 8 weeks were found to be a significant predictor of self-reported activity at 12 weeks, contributing 14.8% of the 34.8% explained variance (R2 change = 0.1479; F = 26.58; P less than 0.0001). Self-efficacy expectations summed for all physical activity at 8 weeks were also significant predictors of self-reported activities at 24 weeks, contributing 8.5% of the variance (R2 change = 0.0847; F = 14.48; P = 0.0002). A New York Heart Association functional class at 4 and 8 weeks was an independent predictor of self-reported activity at 12 weeks, as was 8 week functional class for self-reported activity at 24 weeks. Mood state did not contribute to explained variance in the regression models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258520 TI - Content areas for cardiac teaching: patients' perceptions of the importance of teaching content after myocardial infarction. AB - This descriptive study was undertaken to investigate patients' perceptions of the seven content areas commonly included in cardiac teaching in terms of how important and how realistic they were for being learned following the experience of an acute myocardial infarction (MI). Lazarus's stress-coping theory was used as a framework for the study. A sample of 30 MI subjects were interviewed before discharge and during early convalescence. Before discharge, subjects rated six out of the seven content areas as "important" for learning. Although the information was considered important, it was not rated as equally realistic to learn. During early convalescence, mean scores under 'important to learn' were slightly lower, but all seven content areas were rated as significantly more realistic to be learned (P less than 0.05). Little variation in patients' perceptions of the importance of teaching content was noted over time. However, there was major variation between their perceptions of how important and how realistic it was to learn the material before discharge. Both dimensions, how important and how realistic, are therefore crucial to consider in cardiac teaching. PMID- 2258521 TI - The effect of systematic care planning after acute stroke in general hospital medical wards. AB - In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease, the functional capacity was followed from the acute stage onwards with a test battery mainly measuring activities of daily living and motor capacity. Systematized care procedures with written care plans in accordance with the nursing process model, together with a booklet of guidelines in stroke care, were introduced during an experimental period in the care of 173 of the stroke victims. The remaining 107 patients received conventional care. The functional improvements were equal from a statistical standpoint in these two groups. However, in the group, which received special activities, there was a significant decrease in bed days, and a slightly larger number were able to return to their own homes. Compared with another stroke population from the same hospital, measured with the same functional instrument 7 years ago, the patients in this study seemed better off from a functional standpoint. For the individual severely disabled patient, the care planning procedures seemed to be valuable and an effective way of promoting communication between different units. The difficulties in introducing new routines for documentation are discussed. PMID- 2258522 TI - The nursing management of elderly patients with pain in the community: study and recommendations. AB - This study is designed to identify factors which influence quality of life for elderly people suffering from painful conditions. It is based upon a theoretical model of control in which mood state is used as the indicator of coping. One hundred and ninety elderly patients took part in semi-structured interviews about their pain and coping experiences, and data were also collected from their nurses in the community. Multivariate statistical analysis revealed that the key determinants of mood were having regrets about the past, being occupied, perceived level of pain control, additional personal problems (notably bereavement) and feeling informed about the painful condition. Active personal coping strategies were identified as more therapeutic than passive strategies. Nurses' data revealed that pain complaints were associated with perceived exaggeration. Few nurses used formal pain assessment. Recommendations for the management of persistent pain in the community are given. PMID- 2258523 TI - The Health-Promoting Self-Care System Model: directions for nursing research and practice. AB - In an effort to theoretically integrate perspectives of self-care and health promotion, the Health-Promoting Self-Care System Model is proposed as a framework for identifying and explaining sequential patterns among factors which influence the decision-making, performance and outcomes of health-promoting lifestyles. The model is based upon a synthesis of elements comprising constructs of the Self Care Deficit Nursing Theory as well as certain factors in the Interaction Model of Client Health Behaviour and the Health Promotion Model. Directions for research and practice provided by the model should encourage the development of a cumulative nursing knowledge base and contribute to the goal of enhancing the health and well-being of persons across developmental and sociocultural contexts. PMID- 2258524 TI - Empathy: a review of the literature with suggestions for an alternative research strategy. AB - Although empathy is regarded as a necessary component of good quality nursing care, defining and measuring empathy have both been fraught with problems. A historical overview helps to explain these difficulties, as nurses have tended to accept the views of psychotherapists uncritically, and have used scales developed for clients in counselling with people who are physically ill. Methodological difficulties combined with the results of studies demonstrating low levels of empathic ability in nurses have culminated in disenchantment with this topic. A framework is used to show why nurses cannot always demonstrate empathic awareness of every patient's need and an alternative approach for exploring the nature of empathy is suggested. PMID- 2258525 TI - A survey of opinion amongst trained nurses and junior medical staff on current practices in resuscitation. AB - An anonymously-completed questionnaire was used to examine the opinions of trained nurses and their junior medical colleagues regarding the resuscitation of a patient following cardiac arrest. Nurses were less satisfied with their pre qualification training and recorded lower scores on a subjective assessment of performance than did the doctors. Those nurses who had attended some post qualification training in resuscitation were significantly more confident of their resuscitation skills. Both doctors and nurses agreed on some frequently encountered problems such as the presence of too many people and the uncertainty of those present of the role they should assume. Doctors recorded poor initial resuscitation and the absence of equipment as common problems significantly more often than did the nurses. Nurses showed a lack of knowledge of the drugs used during a resuscitation: 30% were unsure of the function of more than half of the drugs. Nearly 20% of nurses showed a similar lack of knowledge with regard to the equipment used. Those having post-qualification training in resuscitation recorded significantly greater knowledge in these areas. Widespread support was shown for the proposed initiation of compulsory resuscitation lectures, the presence on each ward of resuscitation equipment and more clearly defined roles for those taking part in the procedure. A requirement for a full-time resuscitation officer is clearly indicated. PMID- 2258526 TI - The Patient Learning Needs Scale: reliability and validity. AB - The article describes the development and initial psychometric evaluation of an instrument to measure patients' perceptions of learning needs at time of discharge from hospital to home. Evaluation of the Patient Learning Needs Scale was based on responses of 301 adults hospitalized with a medical or surgical illness. Factor analysis isolated seven subscales: medications, activities of living, feelings related to condition, community and follow-up, treatment and complications, enhancing quality of life and skin care. These seven factors accounted for 56.1% of the variance. Cronbach's alpha for the 50-item scale was 0.95. PMID- 2258527 TI - Combining cognitive therapy and pharmacotherapy in treating depression on an in patient basis. AB - The authors present a case of a 40-year-old female with a history of recurrent unipolar depression in which combined treatment with cognitive therapy and medication was associated with significant clinical improvement. Rather than providing a straightforward example of combined interventions for depressed inpatients, it is hoped that some of the complexities involved in such an endeavour will be highlighted. Specifically, issues concerning planned communication between relevant staff, orientation of ward staff to nonorganic treatments, choice of treatment targets, and potential strains in the collaborative relationship between the cognitive therapist and treating physician are explored. PMID- 2258528 TI - An investigation of recognized incontinence within a health authority. AB - Incontinence affects a very large proportion of the population bringing with it considerable physical, social, psychological and often financial implications for the sufferer. Hence, it poses a considerable challenge to the providers of health care in relation to service provision and appropriate treatment of the problem. This descriptive study focused on the service provided by one health authority to sufferers of incontinence. The service in operation prior to the study had mushroomed with little thought being given to its organization or management, with the result that little was known about the people receiving the service. The study was commissioned to establish the number of people receiving assistance and the nature of the assistance given. Data were collected using pre-existing records, by questionnaire and by interview. A total of 847 people were found to receive assistance from the health authority, the majority of these being female and over the age of 65. Less than half of the study population were in regular contact with the community nursing service with regard to their incontinence. Of the remainder, inadequate incontinence products were found to be supplied without prior assessment of the problem to a proportion of the study population. Some strategies used by this group to manage their incontinence, disclosed during interview, were considered to be detrimental to the general health and well-being of the individuals practising them. These include non-compliance with prescribed diuretics and self-restriction of fluids. The service provided was considered to be a basic one providing assistance to 0.47% of the population of the study area. The implications of the service provided, highlighted by the findings, are wide reaching in terms of the resultant underprovision which led to increased misery for some sufferers and the employment of inappropriate coping strategies. PMID- 2258529 TI - The learner-centredness of two registered general nursing and two registered mental nursing courses as perceived by third-year nursing students. AB - Using the conceptual framework of the Nottingham Andragogy Group, two first-level British courses in general nursing and two in psychiatric nursing were studied to investigate their degree of perceived learner-centredness. Boydell's Scale for Measuring the Learner-Centredness of a Course was administered to a non-random sample of all 172 third-year students at three schools of nursing. Preference for learner-centred nursing education was investigated using Boydell's Preferred Teaching Style Rating Scale with the student sample and by 31 nurse teachers. Results indicated that first-level nursing courses were perceived to be highly teacher-centred in terms of planning, direction, sequence, pace and evaluation of learning. The climate of learning proved to be moderately learner-centred though teacher-student relationships were perceived as formal. Variety of learning approach was seen as limited with a tendency towards positivism rather than relativism of knowledge. Both students and teachers of nursing expressed a slight preference for teacher-centred courses despite the former's dissatisfaction with lack of participation in determining learning objectives. Significantly greater perceived learner-centredness of a psychiatric course was attributed to variations in the philosophy of learning within a particular school rather than to the course per se. PMID- 2258530 TI - Status passage into nursing: another view of the process of socialization into nursing. AB - A status passage is the process of change from one social status to another and, in this report, transition into the occupational role of nurse is described. The status passage includes the anticipations, entry, reporting of contrasts and changes which are often accompanied by surprise, and reality shock before making sense of the passage some months later. Subpassages are noted, and in particular the subtle process of divestiture which results in loss of personal identity. Personal identity is sought through patients and those outside the institution. Occupational role identity occurs between 6 and 10 months after entry into nurse training. The status transition is easier for those with higher self-esteem and lower anxiety scores. The study involved four cohorts of trainee nurses during their first year of training in two schools of nursing, and the study was undertaken using multiple research methods. Present and future policy implications are noted. PMID- 2258531 TI - Theory Z as a framework for the application of a professional practice model in increasing nursing staff retention on oncology units. AB - Recruitment and retention of nurses is the most significant issue facing nursing administrators, educators, researchers and clinicians in the ongoing nursing shortage in the United States today. It has been cited in the literature that American nurses feel that job satisfaction is a major issue in retaining qualified nurses in hospitals. Satisfaction occurs when nurse expectations are matched with the hospital's vision and values. It is for this purpose that the authors have chosen theory Z as a hospital management model to coincide with the institution of the Marker Professional Practice Model to increase job satisfaction (autonomy) in hospital-based nurses. There are four 'hidden' challenges in health care today. They are: (a) fundamental changes occurring within the profession and practice of nursing; (b) the expanded role of women in management; (c) ethical dilemmas related to advances in medical technologies; and (d) the difficulty for health care managers in the United States to make changes related to the above three challenges. The authors feel that it is inherent to the nursing profession to combine existing theories and models to enhance the retention of nurses to the profession. PMID- 2258532 TI - Symposium on Advances in Clinical Nutrition. The American College of Nutrition's 31st annual meeting. October 13-15, 1990, Albuquerque, New Mexico. Proceedings. PMID- 2258533 TI - Food uses and health effects of corn oil. AB - This review of corn oil provides a scientific assessment of the current knowledge of its contribution to the American diet. Refined corn oil is composed of 99% triacylglycerols with polyunsaturated fatty acid (PUFA) 59%, monounsaturated fatty acid 24%, and saturated fatty acid (SFA) 13%. The PUFA is linoleic acid (C18:2n-6) primarily, with a small amount of linolenic acid (C18:3n-3) giving a n 6/n-3 ratio of 83. Corn oil contains a significant amount of ubiquinone and high amounts of alpha- and gamma-tocopherols (vitamin E) that protect it from oxidative rancidity. It has good sensory qualities for use as a salad and cooking oil. Corn oil is highly digestible and provides energy and essential fatty acids (EFA). Linoleic acid is a dietary essential that is necessary for integrity of the skin, cell membranes, the immune system, and for synthesis of icosanoids. Icosanoids are necessary for reproductive, cardiovascular, renal, and gastrointestinal functions and resistance to disease. Corn oil is a highly effective food oil for lowering serum cholesterol. Because of its low content of SFAs which raises cholesterol and its high content of PUFAs which lowers cholesterol, consumption of corn oil can replace SFAs with PUFAs, and the combination is more effective in lowering cholesterol than simple reduction of SFA. PUFA primarily lowers low-density-lipoprotein cholesterol (LDL-C) which is atherogenic. Research shows that PUFA has little effect on high-density lipoprotein cholesterol (HDL-C) which is protective against atherosclerosis. PUFA generally improves the ratio of LDL-C to HDL-C. Studies in animals show that PUFA is required for the growth of cancers; the amount required is considered to be greater than that which satisfies the EFA requirement of the host. At this time there is no indication from epidemiological studies that PUFA intake is associated with increased risk of breast or colon cancer, which have been suggested to be promoted by high-fat diets in humans. Recommendations for minimum PUFA intake to prevent gross EFA deficiency are about 3% of energy (en%). Recommendations for prevention of heart disease are 8-10 en%. Consumption of PUFA in the United States is 5-7 en%. The use of corn oil to contribute to a PUFA intake of 10 en% in the diet would be beneficial to heart health. No single source of salad or cooking oil provides an optimum fatty acid (FA) composition. Many questions remain to be answered about the relation of FA composition of the diet to various physiological functions and disease processes. PMID- 2258534 TI - Isomeric trans fatty acids in the U.S. diet. AB - Since actual consumption data for trans fatty acid (FA) intakes for the U.S. population do not exist, estimates of trans fatty acids (FAs) available in the U.S. food supply have been calculated from U.S. Department of Agriculture Economic Research Service (USDA-ERS) fats and oils production figures and food disappearance data for fats and oils. Based on weighted averages for the trans levels in each fats and oils category, these estimates of trans FAs available in the U.S. food supply range from 12.5 to 15.2 g/person/day (average 13.3 +/- 1.1 g/person/day). Estimates of trans FA consumption have been calculated; these estimates predict a wide range from 1.6 to 38.7 g/person/day. These calculations are based on published estimates of trans FAs available in the total fat of 5 15%, and the total fat intake (range 31-258 g/person/day) of a representative sample of adults (ages 20-59) as determined by the Lipid Research Clinics (LRC). Using an equation based on a relationship between trans FAs in adipose tissue and dietary fat, an intake range of 0.7-28.7 g/person/day trans FAs for the same LRC fat consumption data can be predicted. Adipose tissue isomer profiles that indicate 90-95% of the trans FAs in the tissues comes from partially hydrogenated vegetable fats and oils allow us to predict a dietary intake range from 11.1 to 27.6 g/person/day trans FAs. The significance of these estimates to nutrition policy is discussed. PMID- 2258535 TI - Use of zinc-copper metabolic interactions in the treatment of Wilson's disease. AB - Zinc acetate is becoming a well-established therapy for the treatment of Wilson's disease. It is excellent for maintenance therapy and for the treatment of the presymptomatic patient. Current evidence suggests that it will also be excellent for the treatment of the pregnant patient. Zinc acts by inducing intestinal cell metallothionein, which binds copper with high affinity, blocking its absorption, and causing its excretion in the stool. We have shown that zinc, even in doses as low as 25 mg daily, negatively affects copper balance. Zinc in doses of 50 mg three times daily, with all doses separated from food, controls the abnormal positive copper balance, blocks uptake of orally administered 64Cu, controls urine and plasma copper, prevents the reaccumulation of hepatic copper, and prevents the development or progression of symptoms of copper toxicosis in Wilson's disease patients. Zinc acetate will probably be licensed in the near future for the treatment of Wilson's disease. We recommend that physicians use urine and plasma copper, and urine zinc, as primary monitoring tools. In contrast to the comfortable situation with maintenance therapy, the initial treatment of acutely ill Wilson's disease patients is not well worked out. Patients with neurological disease often get worse initially on penicillamine, and zinc acts more slowly than is ideal. We have initiated studies of tetrathiomolybdate for this purpose. Studies of biliary secretions of normal subjects suggest that they excrete regulatory (excess) copper packaged in a protease-resistant ceruloplasmin fragment. This fragment is missing in Wilson's disease bile. The gene for Wilson's disease is on chromosome 13, close to the retinoblastoma locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258536 TI - Antiarrhythmic short-term protective magnesium treatment in ischemic dilated cardiomyopathy. AB - The efficacy of magnesium sulfate (MgSO4) infusion in the treatment of ventricular arrhythmias was evaluated in 10 normomagnesemic patients: seven men and three women, aged 56-78 years (mean +/- SD, 63.8 +/- 9.3). All of the patients had ischemic dilated cardiomyopathy (IDC) and severe ventricular arrhythmias: multiform ventricular premature contractions (VPCs), couplets, runs of ventricular tachycardia (VT), and R-on-T phenomenon. Four had evidence of old myocardial infarction (MI), four had chronic ischemic cardiomyopathy, and two had effort angina pectoris. Dilated cardiomyopathy was diagnosed by chest X-ray (cardiothoracic ratio greater than 0.5) and echocardiogram (end-diastolic left ventricular diameter greater than 56 mm). All of the patients underwent two successive 24-hr Holter monitoring at the time of admission and after 3, 5, and 10 days from the beginning of therapy. Ventricular arrhythmias were classified according to modified Lown criteria. Renal function was normal. Magnesium sulfate in 0.9% sodium chloride was given by slow infusions (50 mg/min/60 min) twice daily for 7 days. They were antiarrhythmic in all of the patients: VPCs and couplets mean values decreased from 7971 +/- 2612 to 321 +/- 141 (p less than 0.001) and from 405 +/- 113 to 7 +/- 4 (p less than 0.001), respectively; VT runs (33.8 +/- 5.8) disappeared by the fifth day of treatment. Both the heart rate and the QTc interval remained unchanged from baseline values. The slow magnesium infusion did not notably raise serum Mg when evaluated immediately after stopping the infusion, as compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258537 TI - Hypothesis: the effect of oral nitrite on blood pressure in the spontaneously hypertensive rat. Does dietary nitrate mitigate hypertension after conversion to nitrite? AB - Increasing doses of nitrite (3.7-14.8 mg/kg BW) were administered via intragastric intubation to 64 spontaneously hypertensive Sprague-Dawley rats. Systemic blood pressure, measured in conscious animals with the tail cuff method, significantly decreased in a dose-related manner 16 and 32 minutes later, and pulse rate slightly increased. Since orally ingested nitrate may be partially converted to nitrite, it seems worthwhile to study correlations between dietary nitrate and blood pressure in experimental animals and man. PMID- 2258538 TI - Excess vitamin A injures the liver. AB - Chronic vitamin A intoxication in a 56-year-old female is reported. Some abnormal blood chemistries included elevated transaminase and alkaline phosphatase, increased cerebrospinal fluid and portal pressure, and elevated vitamin A in blood and liver. A liver biopsy indicated histologic evidence of perisinusoidal collagen deposition and noncoalescent fat droplets in Ito cells. Caution against the misdiagnosis of alcoholic cirrhosis for vitamin A intoxication is recommended. PMID- 2258539 TI - [5-Fluorouracil and trabeculectomy. A trial of low doses]. AB - Postoperative subconjonctival 5-Fluorouracil (5 FU) may enhance the surgical outcome of trabeculectomies in eyes at high risk of operative failure. 23 patients who received postoperative low doses of subconjonctival 5 Fluorouracil (5 FU) have been studied with a mean follow-up of 10 months. Our indications were: risk factors for a trabeculectomy; postoperative pressure remaining high or absence of filtering bleb. The results were: 42% of complete success (IOP less than 21 mmHg without addition therapy); 29% of qualified success (IOP less than 25 mmHg with additional therapy, or 21 mmHg less than IOP less than 25 mmHg without therapy); 29% of failure. The most frequent complications are corneal, but healed within a short period. The efficacity of the drug remains even with low doses, and with less complications. PMID- 2258540 TI - [Iris vascular anomalies: angiographic aspects]. AB - The authors report five cases of abnormal iris vessels observed in patients, without evident local or systemic pathology. These vessels, are dilated channels. On iris fluorescein angiography their filling appeared earlier than in normal stromal vasculature and was synchronous with that of conjunctival vessels. No dye leakage was present. Two functional angiographic pictures are observable: 1) vessels with abnormal diameter and path, approximately following normal iris vessel arrangement (case 1 and 2); 2) atypical vessels with wide communicating shunt between artery and vein without collaterals (cases 3, 4 and 5). These vessels are very tortuous and do not show any abnormality. The authors suggest to consider these anomalous vessels as anatomic abnormalities comparable with the arterio-venous communications of the retina. PMID- 2258541 TI - [Exfoliation syndrome: clinical study of the irido-corneal angle]. AB - A prospective clinical study of the anterior chamber angle was performed in 263 eyes (152 patients) with pseudoexfoliation syndrome (PSX). No significant difference was found in width and depth of the anterior chamber in comparison with normal population. We found a significative correlation (p less than .0001) between the increase of intraocular pressure (IOP) and the degree of diffuse pigmentation in trabecular meshwork and the Sampaolesi line. When we confronted the two eyes of the same patient, we found that the IOP was greater in the eye with higher pigmentation; and the higher was the difference of pigmentation between the two eyes, the higher was the difference in IOP (p less than .0001). No relation was found between PSX material in angle and IOP. In 24.7% of eyes, we noticed large iris processes, without goniodysgenesis. The results show a significative correlation between the pigmentation of the trabecular meshwork and the IOP. PMID- 2258542 TI - [Toxicity of ethylene oxide on the crystalline lense in an occupational milieu. Difficulty of epidemiologic surveys of cataract]. AB - Ethylene oxide is a sterilizing gas for heat-sensitive materials. Eight cases of subcapsular cataract were attributed to this compound from 1982 to 1985. This epidemiological study was conducted in 55 persons to determine the prevalence of lens opacities and cataracts in workers exposed to this gas. The 21 persons of more than 45 years of age were then compared to 16 non-exposed persons matched for age and gender. Lens opacities (independently of visual acuity) were observed in 19 of the 55 exposed. Among exposed and non-exposed persons of more than 45 years of age, there were no significantly differences with regard to the following characteristics of lens opacities: prevalence (13 in the 21 exposed; 10 in the 16 non-exposed), distribution of the localisations, morphology and importance of the cortical opacities. No link was found between the characteristics of the lens opacities and the characteristics of the exposure: habitual exposure and accidental overexposures. For cataracts, defined by the association of lens opacities and a visual acuity less than 20/25 (this loss not being attributable to another cause), their prevalence differed significantly (p less than 0.05) between the exposed (6 of 21) and the non-exposed (0 of 16). There was no relation between their existence and accidental overexposures. The risk of lens opacification by ethylene oxide, established in cases of massive exposures as previously described, could also exist during chronic exposure to low concentrations, but is to be confirmed by other studies. It could be explained by saturation of the protective mechanisms against alkylating action of this product. This study prompted us to discuss the epidemiological difficulties in studies of cataracts. PMID- 2258543 TI - [Ophthalmologic manifestations of AIDS in an African milieu. Report of 45 cases]. AB - Acquired Immune Deficiency Syndrome (AIDS) is a pathological entity whose agent is a virus called HIV (Human Immunodeficiency Virus). The principal immunological deficit is the insufficience of immunity in mediation cell. Actually AIDS can be considered as the "bubonic plague" of the 20th century. Eye lesions caused by AIDS could present in 54 to 94% of patients of AIDS (3,19). Eye symptoms can be classified into four main categories or groups: retinal vascular lesions, eye opportunist infections, neoplasms of the eye surface and the orbit and finally neuro-ophthalmological anomalies. This study was realised at the university clinic of Mont Amba in Kinshasa, Zaire. A total of 45 cases were studied of which 42 cases with full blown AIDS (1 Congolese, 3 Ruandese, 1 Zambian and 37 Zaireans) and the other three were HIV positive (all were Zaireans). Among the 45 cases, 20 were studied retrospectively with a counting down of 5 years, and 25 others comprised of a prospective group of study or research. The patients were seen either in an ophthalmology Department/Service, or in a medical Service/Centre or in both. The criteria of diagnosis of AIDS were almost the same: skin anergy, infections and/or neoplasm opportunists, the lymphopenia T4, the report T4/T8 low or inversed and the HIV serology positive. A complete opthalmological test was undertaken, the indirect ophthalmoscopy and the retina fluorography were not done. A sex ratio is 1,64 (28 men for 17 women). The 45 patients were sexually active heterosexuals. None of them used drug intravenously. No accidental case of blood transfusion was revealed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258544 TI - [Visual evoked potentials in ophthalmologic practice]. PMID- 2258545 TI - [Submacular neovascular membrane and drusen of the optic disk]. AB - A case of unilateral serous hemorrhagic maculopathy with a very acute course is reported in an eight year old girl fluorescein angiography revealed the presence of a subretinal neovascular membrane extending from the inferotemporal part of the disc to the macula; CT scan identified calcified drusen of the optic disc. Ophthalmoscopy and angiography one year later showed a glial macular scar, absence of hemorrhage and serous detachment. Visual acuity was reduced to counting fingers. This unusual type of maculopathy combining optic disc drusen and a neovascular membrane contradicts the classically benign prognosis of optic disc drusen. PMID- 2258546 TI - [Lacrimal duct injury]. PMID- 2258547 TI - [Use of perfluoro-octane liquid in the treatment of giant tears with inversion of the retina: preliminary results]. AB - Five consecutive cases of giant tears with retinal inversion were easily and successfully treated using vitrectomy and silicone oil injection after repositioning of the retina with perfluoro-octane. The good initial results show the interest of this technique compared with the incarcerations or with the manipulation of the retina and of the perfluoro-octane compared with the other liquid perfluorocarbons. PMID- 2258548 TI - [Scanning laser ophthalmoscopy. Its value in macular diseases]. AB - The scanning laser ophthalmoscope provided a high quality television image of the fundus with minimal illumination of the retina. This new device based on a totally new electro-optical principle allowed a detailed exploration of macular function directly under simultaneous fundus control. The focused beam of a yellow krypton laser (568,2 nm) was swept up and down, rights and links across the fundus to form a raster of parallel lines on the retina. The S.L.O. illuminated only a single retinal point at a time and illumination was reduced to less than 70 microw/cm2 versus 100,000 microns/cm2 for indirect ophthalmoscopy and 4,000,000 microw/cm2 for fluorescein angiography. The intensity of the laser beam could be modified with the microcomputer by means of an acousto-optic modulator. It was possible to produce static or dynamic graphic designs that were simultaneously viewed by the patient and observed by the examiner on the patient's fundus on the video monitor. Further computerized analysis of the videotaped scanning laser ophthalmoscopic images gave a functional retinal map with correction for shifts of stimulus position due to fixational saccadic eye movements. The map showed true retinal location of 1. fixation area; 2. scotoma. The clinical evaluation was completed with 3. measurement of visual acuity in any foveal or parafoveal location. The results of scanning laser ophthalmoscopy were illustrated with the report of datas in a patient with diffuse retinal pigment epithelial decompensation. PMID- 2258549 TI - [Treatment of facial spasm with botulin A toxin]. AB - The authors use injections of botulinum A toxin in treatment of facial spasms. 105 patients (70 patients with blepharospasm, 35 patients with hemispasm) were treated during 4 years. The toxin Wisconsin relieved spasms for an average of 10 weeks. Local complications such as ptosis and diplopia appeared in less than 1/5 of the cases. No general complications were observed. Repeated treatments are necessary. The authors noted a decrease of lacrimal secretion on the treated side in hemifacial spasm and concluded that botulinum A toxin injections could be used as a treatment of epiphora. PMID- 2258550 TI - [Rotational penetrating autokeratoplasty. Report of 10 cases in West Africa]. AB - The authors presented 10 patients (1 bilateral) of central corneal scars treated by ipsilateral rotating autokeratoplasty in West Africa. By rotating an excentric corneal button, the scar could be displaced peripherally and clear cornea brought into the visual axis. The method may be indicated when a non progressive central scar was present in a otherwise clear and normal cornea. The method of Bourne and Brubaker could be useful for determining the most appropriate trephine size and placement. Good visual results were obtained for 7 eyes. Complications undergone in three eyes. The procedure alleviates difficulties with the availability of donor tissue and with graft rejection. PMID- 2258551 TI - [Long-term course of indirect traumatic ruptures of the choroid]. AB - During the last 10 years, 46 cases of indirect choroidal tears were observed with repeated photographies and fluorescein angiographies. Patients were essentially young men with a mean age of 21.7 years. Choroidal tears were mostly single (61%), localized in the temporal part of the optic disc (63.1%), crescent shaped (77.4), and extra-foveal (96.4%). Ten of the 37 cases with a follow-up developed a neo-vascular membrane. Two of these were extra-foveal and were successfully treated with Argon Laser photocoagulation. Sub-retinal neovascular membranes as well as various other complications related to the trauma, such as macular hole, sub-retinal fibrosis and atrophic changes of the retinal pigment epithelium in the macular area, were responsible for a final visual acuity less than 0.2 in 38% of the cases. The influence of the fragility of Bruch's membrane on the number of choroidal tears was evaluated by the relation between the age of the patients and the number of tears, younger patients presenting more often single choroidal tears: the difference is nevertheless not statistically significant. A careful follow-up with repeated fluorescein angiographies is recommended for at least the 2 years following the trauma. PMID- 2258552 TI - [Neuro-anatomy of retinoblastoma]. AB - In four cases of retinoblastoma examined with the method of Golgi we have only found vessels and glial elements at different stages of differentiation. Moreover, in the areas containing typical rosettes, Golgi method revealed some isolately impregnated elements resembling photoreceptors in evolution. Within the retina abuting on the tumor were found only normal retinal nervous elements. Some nervous elements were found also in areas where the tumor tissue intermingled with infiltrated neighbouring retina. PMID- 2258554 TI - [Tachistoscopy: an experimental method for studying cerebral hemispheric specialization]. AB - Tachistoscopy is an experimental method used to study processes involved in hemispheric specialisation and the lateralisation of cerebral functions. The authors review the various findings emerging from this technique and briefly assess its methodological constraints. PMID- 2258553 TI - [Rapid imaging in orbito-ocular pathology. Contribution of gadolinium]. AB - To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology. PMID- 2258555 TI - [Tachistoscopic reading of arabic words]. AB - The authors study the tachistoscopic recognition of Arabic words in Arabic speakers. This study shows that Arabic words are read by Arabic speakers in the same way as French words by French speaking readers. Under such circumstances, the direction of reading appears to be less important than hemispheric specialisation. PMID- 2258556 TI - [Toxocara canis in apparently bilateral ocular site]. AB - The authors report a rare case of ocular larva migrans lesions due toxocara canis in an 8-year-old child. Lesions were bilateral, consisting of peripheral chorioretinal granuloma, papillitis and vasculitis. Diagnosis was confirmed by eosinophilia (37%), positive serology in blood and aqueous humour and by raised immunoglobulins E in vitreous humour. The presence of vascular and chorioretinal lesions was demonstrated by fluorescein angiography. The patient was treated with antihelminthic drugs, topical and systemic steroids and ocular cryotherapy to the peripheral chorioretinal granuloma. The outcome was good, with lesions stabilised. PMID- 2258557 TI - [A good vision in spite of a multifocal implant?]. PMID- 2258558 TI - Anesthetic considerations for pediatric podiatric surgery. AB - The author reviews anesthetic considerations for the pediatric patient requiring foot and lower leg surgery. He initially describes the physiologic and psychologic differences from adults. Preoperative, intraoperative, and postoperative factors are then evaluated. PMID- 2258559 TI - Modified crescentic osteotomy in children. AB - A crescentic osteotomy of the first metatarsal is unstable during the preliminary healing stage. The authors present a modification in the direction of the cut of the osteotomy. This alteration increases stability at the first metatarsal base. PMID- 2258560 TI - Pediatric aneurysmal bone cyst of the ankle. AB - The case report of a large aneurysmal bone cyst of the ankle is presented, as it occurred in a 10-year-old male. Radiographic and histologic characteristics are illustrated. Treatment was by surgical curettment and autogenous bone grafting. PMID- 2258561 TI - Understanding the pathologic Haglund's deformity. AB - Pathologic conditions behind the calcaneus are common, and may initiate during early childhood. The authors discuss osseous and soft tissue conditions involving the posterior-superior surface of the heel. Radiographic and clinical evaluation is considered. Treatment alternatives are also reviewed. PMID- 2258562 TI - Complete subtalar release in clubfeet. AB - Complete subtalar release was performed in 18 children with 22 clubfeet between 1987 and 1989. The ages of the patients ranged from 3.5 months to 8.5 years. The patients were evaluated at 9 to 30 months (average 19 months). Twenty procedures were performed through the Cincinnati incision, and the remaining two through two separate posteromedial and posterolateral incisions. At 6 weeks, the pins were removed and cast immobilization was discontinued at 3 to 3.5 months. Complications were superficial necrosis in three feet, and extensive posteromedial skin necrosis in one foot. No recurrences were encountered. Overall results were very good in 18, and good in four feet. PMID- 2258563 TI - Silastic tendon graft: its role in neglected tendon repair. AB - A case history is presented of the repair of a neglected traumatic tendon laceration by the use of a permanent Silastic tendon implant, originally manufactured for hand surgery by a staged procedure. Stage I consists of implantation of the Silastic implant and allowance of a 2- to 3-month period for the production of a pseudosheath. Stage II consists of removal of the implant after using it to guide an auto- or allograft, through the newly formed pseudosheath for attachment to the anastomotic sites. PMID- 2258564 TI - Assessment of etiologic factors in the development of Freiberg's disease. AB - The etiologic factors in the development of Freiberg's disease are assessed in a consecutive series of 31 patients (33 feet). No evidence was found for the commonly held view that the condition is precipitated by trauma (in only 5 feet (15%), was there a history of injury to the foot). Similarly, pedobarographic studies failed to show high pressure at the affected metatarsal head. However, in 28 feet (85%), the affected metatarsal was the longest in the foot. The importance of this and other possible etiologic factors is discussed. PMID- 2258565 TI - Magnetic resonance imaging of calcaneal aneurysmal bone cyst. AB - A 7-year-old black male presented with a lytic, expansile lesion of the calcaneus. This lesion was studied with conventional x-rays as well as MRI. The MR examination demonstrated a multiloculated lesion with material of a high- and low-signal intensity appreciated within each loculation. Pathologic review of the lesion demonstrated an aneurysmal bone cyst. PMID- 2258566 TI - Enigma of pediatric vertical talus deformity. AB - Vertical talus is an unusual pediatric deformity that often is unrecognized at birth. Its treatment is necessarily surgical and not typically addressed by the podiatric medical profession. In this case report, the enigmatic deformity is reviewed, along with a detailed photographic assay of useful techniques for its surgical reduction. PMID- 2258567 TI - Role of epiphysiodesis in the management of deformities of the foot and ankle. AB - Dynamic correction of orthopedic deformities of the foot and ankle may be performed by epiphyseal growth retardation, or arrest. These procedures lend themselves to the management of juvenile hallux abducto valgus with metatarsus primus adductus, and ankle valgus in particular. Historical review, indications, timing, and technique are addressed in this manuscript. PMID- 2258568 TI - Complete duplication of an accessory first ray. AB - A case report of an accessory metatarsal located between the first and second metatarsals is presented. This rudimentary accessory ray caused a splay foot deformity that made it difficult for the patient to walk comfortably in shoes. In reviewing the literature, there has been very little reported on the complete duplication of a metatarsal, as described by Venn-Watson. The authors will discuss the proper treatment of, and review the classifications associated with, this deformity. PMID- 2258569 TI - Tarsal coalition: etiology, diagnosis, and treatment. AB - Tarsal coalition has been recognized as a pedal anomaly for hundreds of years. Consistent research through the years has led to new advances in the understanding of this problem. New ideas concerning etiology, incidence, diagnosis, and treatment have necessitated a review of the most recent literature concerning tarsal coalition and its associated disorders. The authors present an update on the current therapies, diagnostic modalities, and corrective procedures involved. This article combines the most current imaging techniques with those traditionally accepted. The authors suggest magnetic resonance imaging (MRI) to replace computerized tomography (CT) scan as the diagnostic imaging technique of choice. An analysis of all the surgical procedures is discussed, and suggestions are made as to the most appropriate approach to this insidious and disabling pathology. PMID- 2258570 TI - Magnetic resonance imaging of pediatric foot and ankle disorders. AB - The authors present magnetic resonance imaging as an accurate modality that is available for evaluating lower extremity pediatric pathology. They examine various disorders, and review proper magnetic resonance techniques. Soft tissue, cartilaginous, and certain osseous abnormalities are inspected. PMID- 2258571 TI - Surgical treatment of osteoid osteoma in an adolescent. AB - The literature is complete in its review of osteoid osteoma and benign bone forming tumors. When present in a child, the clinical and radiographic picture is not that clear and often is missed diagnosed. Routine radiographs may not offer a complete diagnosis in this young patient and additional studies are indicated. Tomograms and computerized tomographic (CT) scans, as well as bone scans, provide more information in determining the presence of absence of a bone lesion in the child. A case is presented of an 8-year-old female with pain for over 10 months, eventually diagnosed as an osteoid osteoma. A surgical procedure was performed to excise the lesion and replace it with a corticocancellous bone graft. The child has been followed for the past 5 years and has remained asymptomatic. PMID- 2258572 TI - Surgical reconstruction of a congenital foot deformity: hallux varus with brachymetatarsia of the first metatarsal. AB - A literature review of the etiologies and treatments of both hallux varus and brachymetatarsia is presented. An unusual case report of a young girl with bilateral congenital hallux varus and brachymetatarsia of the first metatarsal is then discussed. A detailed account of the surgical correction consisting of autogenous bone grafts from adjacent metatarsals proved to demonstrate excellent biomechanical and cosmetic results. PMID- 2258573 TI - Treatment of skewfoot by multiple lesser tarsal osteotomies and calcaneal osteotomy. AB - A 9-year-old male with bilateral skewfoot deformity underwent corrective surgery consisting of multiple abductory, lesser tarsal osteotomies, and medial displacement L-shaped calcaneal osteotomy. The author prefers this surgical approach because it minimizes shortening of the lateral column without limiting the amount of transverse plane correction. The calcaneal osteotomy offers excellent stability in the sagittal plane without limiting frontal or transverse plane correction. PMID- 2258574 TI - Ankle arthroscopy in the adolescent patient. AB - The author reviews 15 cases of ankle arthroscopy in adolescent patients. Most of the patients were female. He discusses the various pathologies identified, with the most common being a medial impingement lesion. Synovitis was present in all cases of persistent discomfort. PMID- 2258575 TI - Effects of active immunization against L-triiodothyronine on serum thyrotropin levels and liver mitochondrial alpha-glycerophosphate dehydrogenase activity in rats: evidence for reduced hormone disposal to cells. AB - Thyroid hormone binding autoantibodies have been observed in serum from patients affected by either thyroid disorders or autoimmune nonthyroid diseases. In most instances, no major involvement of thyroid status of these patients has been reported. However, some authors have attributed the occurrence of hypothyroidism to high capacity thyroid hormone binding autoantibodies. In order to verify such a hypothesis, the effect of these autoantibodies on serum TSH and liver mitochondrial alpha-glycerophosphate dehydrogenase has been investigated in rats, wherein circulating T3-binding antibodies (max cap 10(-12) 10(-8) to mol/l) were induced by active immunization. Starting from the 3rd week after antigen injection, the binding of 125I-T3 to serum immunoglobulins was progressively increased, with a peak at the 5th week. In immunized animals considered as a whole group, serum TSH levels were significantly higher and liver mitochondrial alpha-glycerophosphate dehydrogenase activity was significantly lower than in normal rats (m +/- SE: 145 +/- 15 vs 34 +/- 2 ng/dl and 0.0450 +/- 008 vs 0.0980 +/- 005 delta A. mg/prot/.min, respectively; p less than 0.001). The pattern of both TSH increase and alpha-glycerophosphate dehydrogenase decrease were similar to the evolution of 125-I-T3 binding to serum immunoglobulins, the maximal TSH values and lowest enzyme levels being observed at the 5th week after the beginning of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258576 TI - GHRH-test in short children with "non classic" GH deficiency. A comparison with "classic" GH deficiency and short normal stature. AB - In this study GHRH-test has been performed (2 micrograms/Kg of an iv bolus of GHRH 1-44) sampling for GH measurement every 15 min over 2 hours in three groups of short children. Group 1 consisted of 10 subjects with classic GH deficiency (CGHD): GH response less than 10 ng/ml to two conventional tests and 24-h mean GH concentration (MGHC) less than 3 ng/ml; group 2 consisted of 16 subjects with non classic GH deficiency (NCGHD): response greater than 10 ng/ml to at least one conventional test and MGHC less than 3 ng/ml; group 3 consisted of 18 subjects with short normal stature: GH response greater than 10 ng/ml to at least one conventional test and MGHC greater than 3 ng/ml. GH peak and area under the curve (AUC) values were significantly lower in group 1 than groups 2 and 3 and in group 2 than group 3. GH peak and AUC values statistically correlated with height, height velocity, bone age/chronological age ratio and MGHC. Six children in group 1, 14 children in group 2 and all 18 children in group 3 showed after GHRH a GH peak greater than 10 ng/ml and were considered as 'responders'. Considering only the responders, GH peak and AUC values were significantly lower in group 1 than groups 2 and 3 and in group 2 than group 3. In conclusion, our data have shown that 87% of children with NCGHD responded to a single bolus of GHRH with an increase in GH levels greater than 10 ng/ml and that their responses were intermediate compared to those of CGHD and short normal subjects. PMID- 2258577 TI - HLA-DR4 associated response to corticosteroids in Graves' ophthalmopathy patients. AB - Fifty-seven patients with severe Graves' ophthalmopathy were treated with corticosteroids. Therapeutic outcome was assessed according to predetermined criteria as response (n = 37) or non-response (n = 20) to therapy. Patients were typed for HLA-A, -B, -C, -DR and -DQ. HLA-DR4 was completely absent in the 20 non responder patients (corrected p value = 0.042). In the responder group 14 of the 37 patients were HLA-DR4 positive. This study shows that in Graves' ophthalmopathy patients the presence of HLA-DR4 is associated with a good response to corticosteroid therapy. The frequency of HLA-DR4 in the Graves' ophthalmopathy population as a whole, however, was not different from normal (25% versus 26%). But as reported previously, the frequency of HLA-DR3 was significantly increased in the Graves' ophthalmopathy patients when compared to healthy blood donors (47% versus 24%, corrected p value = 0.02). No significant deviations were found in the HLA-A, -B, or -C loci. PMID- 2258578 TI - Calcitonin secretion rate in elderly normal subjects. AB - The aim of the study was to investigate the metabolic clearance rate (MCR) and the secretion rate (SR) of calcitonin (CT) in elderly men and women (mean age +/- SE: 75 +/- 3 and 78 +/- 3 yr, respectively). The basal levels of CT were higher in men than in women (9.6 +/- 3.2 vs 6.0 +/- 1.5 pg/ml; p less than 0.05). The MCR was not significantly different between sexes (905 +/- 54.2 vs 810 +/- 165.1 l/day). In contrast, CT SR was significantly higher in male subjects compared to women (8.7 +/- 3.1 vs 4.8 +/- 1.5 micrograms/day; p less than 0.05). These findings suggest that only a few units of CT are secreted daily by elderly subjects and that the lower basal values of the hormone in women are probably the result of a lower production rate. PMID- 2258579 TI - Inhibitory effects of centrally administered /ASU1-7/eel calcitonin on basal and stimulated prolactin release in rats. AB - We investigated the effects of /ASU1-7/eel calcitonin (ASU1-7eelCT) on basal and stimulated prolactin (PRL) release in male rats. /ASU1-7/eelCT was administered intracerebroventricularly (icv) into freely moving rats with indwelling catheters. The administration of /ASU1-7/eelCT (2.5 micrograms/rat, icv) significantly inhibited basal PRL secretion. When PRL secretion was stimulated by exposing rats to restraint stress, /ASU1-7/eelCT (250 ng; 800 ng; 2.5 micrograms/rat, icv) dose-relatedly inhibited the PRL surges at 10 min after stress. The same doses of icv /ASU1-7/eelCT were effective in inhibiting morphine (6 mg/kg, intracarotid, ia-induced PRL release. No effect on stress-induced PRL secretion was observed when the peptide was administered intracarotid at the dose of 10 micrograms/rat. These results demonstrate that /ASU1-7/eelCT, as we previously observed with salmon calcitonin (sCT), has central inhibitory activity on PRL secretion, probably through enhancement of hypothalamic inhibitory pathways involved in the control of PRL. PMID- 2258580 TI - A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves' hyperthyroidism. AB - The outcome of radioiodine therapy of Graves' hyperthyroidism was retrospectively evaluated in 274 consecutive patients treated from 1975 to 1984. At 1-yr follow up, permanent hypothyroidism occurred in 36.9% of patients and the cumulative incidence of hypothyroidism progressively increased up to 79.3% after 7-10 yr. At the end of the follow-up period, 148 patients (54%) were hypothyroid, 115 (42%) euthyroid and 11 (4%) still hyperthyroid. The prevalence of hypothyroidism was significantly higher in patients with small goiters (less than or equal to 50 g) than in those with large goiters (greater than 90 g). Moreover, hypothyroidism was more frequent in patients with high thyroglobulin antibodies titers (greater than or equal to 1:25,600) than in those with low titers or negative tests, and occurred earlier in the former group than in the latter ones Correction of thyrotoxicosis was obtained after the administration of a single dose of 131I in 187 patients (63.6%); 69 patients required two doses and 11 three or more doses. Seven patients refused further treatment with 131I after the first dose. In an effort to identify possible factors affecting the efficacy of 131I therapy, we evaluated the results obtained after the administration of the first dose of radioiodine. We found that large goiters, rapid iodide turnover and adjunctive therapy with methimazole shortly after radioiodine were associated with a higher rate of persistence of thyrotoxicosis, whereas an increased prevalence of hypothyroidism was observed in patients with small goiters and in those not treated with methimazole up to one week after 131I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258581 TI - Spontaneous regression of anterior pituitary deficits in a woman harboring a persistent hypothalamic mass. AB - Sellar or parasellar lesions can cause anterior pituitary dysfunction either by direct damage to the anterior pituitary gland or by compression of the pituitary stalk and mediobasal hypothalamus which contain the hypophysiotropic hormones. Without treatment, the pituitary deficits in such cases are not likely to improve. We describe a case in which deficits in anterior pituitary hormones spontaneously remitted in a woman who had a persistent hypothalamic lesion that was not amenable to surgery or radiotherapy. The factors that may predict spontaneous recovery of anterior pituitary function in such cases are discussed. PMID- 2258582 TI - Amiodarone-induced thyrotoxicosis suggestive of thyroid damage. AB - Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT. PMID- 2258583 TI - Effect of acipimox, a lipid lowering drug, on growth hormone (GH) response to GH releasing hormone in normal subjects. AB - Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GH-releasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 micrograms iv The GH response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo. In subjects receiving placebo, but not in those receiving acipimox, a progressive increase of plasma FFA levels took place, and the GH response to GHRH was inversely related to the plasma FFA levels at 0 min. These data indicate that FFA play an important role in the control of GH release, and that acipimox prevents the FFA rise induced by GH. PMID- 2258584 TI - [Multiple pregnancies. III. Therapeutic, psychologic and social aspects]. AB - The authors analyse a series of 23 multiple pregnancies (19 triplet pregnancies, 3 quadruplets and 1 quintuplet). The first objective is to fight prematurity. Over and above all use of drugs as tocolytics (beta-mimetic drugs and progesterone) should routinely be advised and as soon as there is any threat of premature labour hospitalisation is needed. Twenty one of the 23 patients had prophylactic cerclage (Shirodkar's stitch). In 77% of the cases respiratory distress in the newborn was avoided by using cortico-therapy. Vaginal delivery can be carried out under certain conditions in triplet pregnancies. If certain precautions are taken there does not seem to be any immediate difference in the post delivery period of these children if they are born vaginally or by caesarean. Perinatal mortality is raised (at 5.6% for triplets and 58.3% for quadruplets). The psychological implications of these pregnancies are important. Problems appear as soon as the diagnosis is made and continue for years afterwards. On the social level, help given by the social services are usually inadequate. If the couples belong to the National Association for Mutual Aid of Parents of Children of Multiple Births, a system of mutual support is available. We recommend that these pregnancies should be looked after by several disciplines. These consist not only of obstetricians, paediatricians, anaesthetists, those who resuscitate together, but also psychologists, dietitians, social workers, community workers and physiotherapists. PMID- 2258585 TI - [Termination of pregnancy called "therapeutic." Requirements, limits and insufficiencies of the law]. AB - The authors point out the difficulties in applying the two final paragraphs of article L 162 of the Public Health Code which authorizes and explains the justification for terminating pregnancies later than the legal term of twelve weeks of amenorrhoea. These difficulties arise mainly because of the different ways in which it is possible to interpret how serious a menace to the health of the woman is caused by the pregnancy, which at present cannot be the only reason for provoking a purely medical decision for terminating the pregnancy while deciding how desperate the obvious distress is. On the other hand, the definition of a strong probability that the child to be born would have a particularly serious malformation, recognised as incurable when diagnosed and which constitutes the second indication for terminating the pregnancy on so called therapeutic grounds seems also to lack precision. The authors draw attention to how strictly the law has to be applied as far as termination of pregnancy is concerned as well as basic conditions for carrying out the procedure, which can act as a support for the sole but very definite precise judgement of the Appeal Court of Paris on the 9th July 1982. This can be considered as a judgement for bidding any deviations form the legal requirements of a text that is a very definite one and has to be interpreted strictly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258586 TI - [Transplacental administration of diethylstilbestrol in the rat. II. Effect on the hormonal receptors of the endometrium]. AB - Transplacental exposure to diethylstilboestrol (DES) strongly decreases the fertility of the offsprings. Progesterone receptors concentrations are significantly decreased for treated group (0.40 and 0.44 pmol/mg cytosol proteins) versus control group (0.74 pmol/mg cytosol proteins) Estradiol receptor concentrations are significantly higher for long time treated groups (0.26 pmol/mg cytosol proteins) versus control or short time treated groups (0.15 and 0.13 pmol/mg cytosol proteins). PMID- 2258587 TI - [The fetal-maternal interface. Description of its elements from an immunologic perspective]. AB - The authors describe the different elements that can change the immunological response at the feto-maternal interface having studied the increasingly large literature on the subject. They consider first the nature of the interface and how trophoblastic antigens occur and then they point out the type and the role played by the different numerous decidual cells that take part in recognising, activating and regulating the immune system there. This general review is justified because local immunological phenomena seem to be important for the survival and the development of the feto-placental unit. They are also for immuno suppressant mechanisms and immuno-tropic mechanisms. These phenomena, however important they may be, make it necessary to recognise one or more embryonic or trophoblastic antigens acting on the maternal immunological system. PMID- 2258588 TI - [Should systematic bone scintigraphy be carried out on breast cancer patients with small tumors?]. AB - Bone metastases are frequent in the evolution of breast cancer. Bone scan is the best method for early detection. At initial presentation the frequency of bone metastases is low, and it is usefulness to recommend this exam except for old people or patients with risks factors. During the follow-up, the utility of repeated bone scan is discussed. For the majority of authors, it may be reserved for symptomatic patients or when biological modifications appeared. The follow-up of these patients must be essentially clinical. This strategy delay the diagnosis of bone metastases of only a few weeks; and it don't seem to affect the prognosis of these patients. PMID- 2258589 TI - [Anamnestic, clinical and urodynamic comparative data from a group of patients with urinary stress incontinence]. AB - Two hundred and seventy seven patients presenting genuine USI were divided into 3 groups based on a positive history for USI (group I), positive history and clinic for USI (group II), and positive history, clinic and urethral profile of USI (group III). When compared to a group of women without USI, the values for the FL and MUCP diminish progressively from group I to group III, giving evidence of increasingly severe impairment of the muscular-elastic environment in the urethra. Only in group III is the transmission factor (F) reduced, attesting a loosening/distension of the posterior pubo-urethral ligaments. The tonomeric values calculated for the patients with recurring USI following previous surgical correction (group IV) are comparable to values for group III. A scoring of severity of USI is proposed serving as a basis for establishing the criteria determining the indication for surgery and the post-operative prognosis before an intervention to correct USI is undertaken. PMID- 2258590 TI - [Neuro-endocrine carcinoma of a Bartholin's gland]. AB - This is a case of a 38 year old woman in whom a small basophil cell tumour occurred with inguinal and iliac lymph node metastases followed by pulmonary metastases and extension of the tumour into the vagina and the bladder. The patient died eight months after having started multiple chemotherapy and radiotherapy with telecobalt. Extra studies were carried out ten years later on the cells. This made it possible to diagnose the condition as a neuro-endocrine carcinoma rich in serotonin. PMID- 2258592 TI - [Intrauterine hydatidosis. A case report]. AB - The authors describe a rare case of an intra uterine hydatid cyst in a 60 year old woman. Hydatid vesicles were found in the vagina. The diagnosis was made histologically. A total hysterectomy was carried out. The authors discuss the aetiology and pathogenicity of an occurrence at this site. Conservative treatment is suggested for young female patients. PMID- 2258591 TI - [Study of the efficacy and tolerance of Iopamiron 370 compared to Telebrix Hystero in hysterosalpingography]. AB - Hysterosalpingography is used to study the state of the uterine cavity as well as to analyse the patency of the tubes and the state of the tubal mucosa. It is difficult to find a contrast medium that has both the ideal qualities, be well tolerated and able to show fine pictures that have good contrasts, while at the same time are sufficiently viscous to allow up examination. The contrasts products that are used to carry out hysterosalpingography are often classed as viscous (Telebrix Hystero) and fluid (Iopamiron). This prospective randomised study compares local tolerance and efficiency of the two products. Fifty patients had Iopamiron and 48 Telebrix Hystero in July 1988 and February 1989. There was a statistical difference between the two groups which was significantly in favour of Iopamiron on the following features: Pain as noted on a questionnaire with steps of five points each (p = 0.02), Pain as described by the patient immediately after the examination on a visual analogue scale with p less than 0.01. Overall appreciation of the two products according to their tolerance and the efficiency of the products, which is to say the clearness of the pictures obtained with a p = 0.05. PMID- 2258593 TI - [The Hellp syndrome: is this a clinical form of thrombotic microangiopathy?]. AB - There are similarities between the clinical, biological and histological features of thrombotic micro-angiopathy (TMA) when it is a complication of pregnancy and the "Help Syndrome" (HS). HS can be associated in pregnancy with pre-eclampsia, thrombocytopenia, micro-angiopathic haemolysis and hepatic cytolysis. We have analysed on the one hand biological features of six cases that occurred in the literature and two personal cases of thrombotic micro-angiopathy that had been proven histologically; and on the other hand the histological findings of the liver in two cases of the literature and in a personal case of HS. Demonstration that in HS deposits exist under the endothelium in the region of the hepatic biopsy suggest that the latter can only be a special clinical form of TMA. PMID- 2258594 TI - [Outcome of 470 pregnancies after artificial insemination with frozen sperm]. AB - This article describes the outcome of the pregnancies conceived after AID with frozen semen in the Tours CECOS Centre between January 1st 1988 and December 31st 1986. There were 487 (including multiple pregnancies). These have been compared with a control group and with the national study conducted by INSERM in 1981. The study of the literature allows comparisons. The rate of pregnancies not resulting in a living child is not significantly different from the control series (abortions 11.4%, ectopic pregnancies 1% and in utero fetal deaths 0.4%). Pregnancies that continued: the rate of multiple pregnancies was higher (2.7%). There were more cases of bleeding (6.8% compared with 2.4%), more hypertensions (13.3% compared with 11.6%) and the same rate of premature labour (9.4%) as in the control group. The Caesarean section rate (22% as against 6%) was higher. The rate of forcepts delivery was lower (9.2% as against 12.8%). Concerning the children we found more premature babies (15.8% versus 5.6%) but no difference in the sex ratio, their height-weight as against their term, their Apgar score, morbidity or number or type of malformations (3.4%). IN CONCLUSION: the quality of the children is about the same with the proviso that the group is too small to conclude about the incidence of chromosomal abnormalities. PMID- 2258595 TI - [Pregnancy and cystic fibrosis. A case history]. AB - The authors report a case of pregnancy in a patient suffering from moderately severe cystic fibrosis (the syndrome consisted of diffused obstruction in respiratory function with a vital capacity of 79% and the lowered blood oxygen level with arterial blood gas estimations; oxygen saturation was 94%). The condition was marked by temporary worsening during the pregnancy in which infective bronchitis supervened). She also threatened to go into early labour and did in fact deliver at 36 1/2 weeks of an infant which was normal for the duration of the maturity. The authors review previous known facts about cystic fibrosis. A study of the literature has made it possible to be more accurate in describing methods of ante natal diagnosis of the condition and ways of following the pregnancy and the illness as well as the woman's fertility and her ability to breast feed. PMID- 2258596 TI - [AIDS: is it an indication for artificial insemination with anonymous donor sperm?]. AB - Such demands raise difficulties, as the physician has to consider (and has to be the defender of) the coming child. A thorough psychological investigation must be conducted, as the couple's motives and those of each partner considered separately are not necessarily in agreement. Most important for the couple are the persistence of common projects and the strengthening of the bonds. The husband wants to survive through a child, to give an ultimate present and to increase the chance of keeping his partner. The wife shows her faithfulness and diminishes her partner's guilt feelings. She is, anyway, in a difficult situation if trying not to become pregnant, especially if she had already expressed a wish for maternity in normal circumstances. Unconscious mechanisms can intervene, such as fantasmatic adultery (through IAD) which reequilibrates the couple: the husband who brought the HIV has to be forgiven, or punished. Also, and most importantly, one has to analyze the prospects for the child, who is at risk of loosing his father, and also his mother: a later transmission of the virus to her cannot be excluded. The child will be confronted by illness and death of his father, and by heavy family secrets. The attitude of the medical team remains problematic: no clearcut attitude prevails. PMID- 2258597 TI - Improving antibiotic use has become essential--can surgery lead the way? PMID- 2258598 TI - Estimated cost of needlestick injuries for six major needled devices. AB - A major factor in the introduction of new products designed to decrease the risk of needlesticks to healthcare workers (HCWs) is whether the increased expense of a safer device is offset by the savings of preventing needlesticks. The itemized costs of needlestick injuries associated with six major needled devices were estimated and compared to the cost of the devices causing the injuries, based on 1988 dollars. Included was the cost of treatment, prophylaxis and employee health department personnel time. The average cost of needlestick injury was $405, with a narrow range of $390 to $456 for different devices. As a percent of the cost of the devices, needlesticks cost as little as 10% of the cost of the device, for the intravenous (IV) catheter, to as much as 457%, for needles used to connect IV lines. On the average, needlesticks cost 36% of the devices' cost. These data may be used to weigh the potential economic benefits of safer needle technology or other strategies intended to reduce the incidence of needlesticks. PMID- 2258599 TI - The role of handwashing in prevention of endemic intensive care unit infections. AB - Handwashing is believed to be the most important means of preventing nosocomial infections. Previous studies of healthcare workers (HCWs) have shown that handwashing practices are poor. No one has shown that handwashing practices can be easily improved and that this prevents endemic (nonepidemic) nosocomial infection. Handwashing and infection rates were studied in two intensive care units (ICUs) of a community teaching hospital. Handwashing rates were monitored secretly throughout the study. After six months of observation, we started interventions to increase handwashing. Handwashing increased gradually, but overall rates before (22.0%) and after (29.9%) interventions were not significantly different (p = .071). Handwashing never occurred before intravenous care, whereas it occurred 67.5% for all other indications (p less than .0001). When questioned, nurses felt they were washing appropriately nearly 90% of the time. Infection rates seemed unrelated to handwashing throughout the study, and no clusters of infection were detected. We conclude that handwashing rates, when measured against arbitrary but reasonable standards, are suboptimal, difficult to change and not closely related to evidence of cross-infection. Further, nurses wash hands selectively, depending on the indication for handwashing, and generally believe they are washing much more frequently than an objective observer believes they are. PMID- 2258600 TI - Importance of neutralizers in the stripping fluid in a simulated healthcare personnel handwash. AB - The Food and Drug Administration (FDA) healthcare personnel handwash procedure allows for the use of a non-neutralizing stripping fluid after washing with an antimicrobial handwash product. The antimicrobial in the handwash product can remain active up until the time of neutralization or plating. A modified healthcare personnel handwash procedure using a pigskin substrate and a 4% chlorhexidine gluconate handwash product was used to demonstrate the need for a neutralizer in the stripping fluid. When tests were run with and without neutralizers in the dilution blanks, but with adequate neutralizers in the stripping fluid, there were no significant differences (p greater than .05) between results obtained after five washes or after each wash. When tests were run with a non-neutralizing stripping fluid, significant differences were noticed in the first and the fifth wash (p less than .05), and in the presence or absence of neutralizers in the dilution blanks (p less than .05). The data generated indicate that in order to determine the true activity of an antimicrobial handwash product, an adequate neutralizer should be incorporated into the stripping fluid and not just the dilution media. They also suggest that neutralizer carry-over from the stripping fluid is not a valid concern. PMID- 2258601 TI - Evaluating the sterility of disposable wall oxygen humidifiers, during and between use on patients. PMID- 2258602 TI - Emporiatrics: diarrhea in travelers. AB - The degree of discomfort and inconvenience caused by travelers' diarrhea highlights the need to prepare the international traveler thoroughly. In addition to observing food and water precautions, most travelers should carry antibiotics and antimotility agents to be started if diarrhea occurs. Used judiciously, these precautions may prevent an unplanned tour of bathrooms and outhouses in foreign countries. PMID- 2258603 TI - Functional studies examining the subpopulation of human B lymphocytes responding to high molecular weight B cell growth factor. AB - Mature human B lymphocytes perform many functions including antibody secretion, Ag presentation, preservation of memory for Ag, and lymphokine secretion. Individual resting B cells receive multiple sequential signals that determine the function(s) that will be performed by those cells. Activation signals such as Ag or Staphylococcus aureus Cowan I (Sac) stimulate overlapping but different subpopulations of B cells. After activation, B cells may be induced to proliferate by a variety of B cell growth factors (BCGF) including IL-2, IL-4, TNF-alpha, low molecular weight BCGF (LMW-BCGF), and high molecular weight BCGF (HMW-BCGF). Little information exists to explain why so many different BCGFs are involved with human B cell proliferation. The current studies were designed to examine the role HMW-BCGF plays in selecting B cells for particular functions. HMW-BCGF but not LMW-BCGF was found to inhibit Ig secretion when it was included in culture with Sac-activated B cells and B cell differentiation factors (BCDFs) including IL-6. Sorting resting B lymphocytes into surface IgD+ and IgD- populations and then stimulating each population with anti-mu revealed that the cells most responsive to HMW-BCGF resided in the surface IgD- sorted population. Sorting activated B lymphocytes into BA5 (HMW-BCGFR)+ and BA5- populations revealed that BA5+ B cells stimulated with BCDF (in the absence of HMW-BCGF) produced predominantly IgG, whereas the BA5- population produced both IgG and IgM. Finally, expansion of peripheral B cells from tetanus toxoid-immunized donors with either HMW-BCGF or LMW-BCGF revealed that the HMW-BCGF-expanded population produced predominantly IgG tetanus-specific antibody in the presence of BCDF (in the absence of HMW-BCGF), whereas the LMW-BCGF-expanded population produced IgM much greater than IgG tetanus-specific antibody. Thus, HMW-BCGF may function to expand a subpopulation of B cells for memory B cell functions. PMID- 2258604 TI - The role of Ia in the formation of a T cell antigen-recognition complex. AB - We have evaluated the ability of a peptide-specific, I-Ak-restricted murine T hybridoma to bind its Ag in the presence and absence of class II MHC molecules. The restricting Ia molecule, when supplied as a plasma membrane preparation of I Ak-expressing APC, specifically increases the avidity of the Ag-binding complex by lengthening its t1/2, without affecting the rate at which the complex is formed. Experiments using mutated I-Ak molecules indicate that the ability of a mutant Ia species to present Ag is distinct from its ability to stabilize the Ag recognition complex, suggesting that T cell stimulation depends not only upon stabilization of Ag-TCR-Ia complexes, but also upon distinct Ia-influenced conformational signals. PMID- 2258605 TI - T cells from nonresponder mice. MHC restricted and unrestricted recognition of insulin. AB - Two types of insulin-reactive T cell hybridomas expressing TCR-alpha beta were derived from nonresponder H-2b mice immunized with pork insulin. One type had characteristics of conventional class II-restricted Th cells. These CD4+ CD8- I Ab-restricted T cells recognized a self determinant, present within the insulin B chain. This determinant was distinct from the immunodominant A-chain loop determinant that is recognized by the majority of T cells induced after immunization with normally immunogenic beef insulin. Our results suggest that this determinant is readily generated during immunologic processing of insulins, including nonimmunogenic pork insulin and self insulin. A second type of T cell lacking CD4 and CD8 recognized a distinct B-chain determinant of insulin in a class II-dependent, but MHC unrestricted, fashion. These cells may represent a novel subpopulation which has bypassed conventional selection during development in the thymus. PMID- 2258607 TI - Antibody-dependent cellular cytotoxicity against HIV-coated target cells by peripheral blood monocytes from HIV seropositive asymptomatic patients. AB - Cytotoxic effector cells like cytotoxic T cells, NK cells, monocytes/macrophages, and neutrophils can lyse directly HIV-infected or HIV-coated cells in the absence or presence of anti-HIV antibodies. Therefore, these cytotoxic mechanisms can be invoked either in the control of HIV infection at early stages of the disease or in the generalized immunosuppression observed at later stages of the disease. The relationship between anti-HIV effector mechanisms and disease, however, remains elusive. The present study investigates in HIV+ seropositive asymptomatic patients peripheral blood monocytes (PBM)-mediated antibody dependent cellular cytotoxicity (ADCC) against HIV-coated target cells in the presence of heterologous or autologous anti-HIV serum. To test for specific ADCC against HIV Ag, a T4+ CEM.TR line resistant to TNF and macrophage-mediated cytotoxicity was selected in vitro. ADCC was performed in an 18-h 51Cr-release assay using CEM.TR cells coated with inactivated HIV. Unlike PBM from normal controls, significant ADCC was observed by PBM from HIV+ seropositive patients in the presence of pooled HIV+ antiserum. The ADCC activity was specific for HIV and was dependent on the E:T ratio and the antiserum dilution used. Upon activation of PBM with rIFN-gamma, both normal and HIV+ PBM-mediated ADCC against HIV-coated CEM.TR. Furthermore, ADCC activity by PBM from HIV+ seropositive patients in the presence of their autologous serum was examined. Significant ADCC activity was observed and was dependent on the E:T ratio and serum dilution used. The findings demonstrating anti-HIV ADCC activity by PBM from HIV+ seropositive individuals and their autologous sera support the notion that monocyte-mediated ADCC may be operative in vivo. PMID- 2258606 TI - Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases. AB - We have devised a luminescence sandwich ELISA for the quantification of IL-6 in both sera and cell culture supernatants, which had a detection limit of 100 fg/ml of test sample. By using the luminescence sandwich-ELISA, low but measurable levels of IL-6 (9.5 pg/ml on average) were found in the sera from normal individuals. The serum levels of IL-6 were elevated in HIV-seropositive asymptomatic carriers (55.5 pg/ml on average), and the IL-6 levels were correlated with the degree of HIV-induced disease progression (AIDS-related complex 106.8 pg/ml on average and (AIDS 283 pg/ml). IL-6 immunoreactivity in the sera of AIDS patients eluted at a 25,000 m.w. major peak, which was biologically active and heat-stable, and a 500,000 m.w. minor peak in size-exclusion HPLC. Interestingly, a significant correlation was observed between the serum IL-6 levels and soluble IL-2R levels. In vitro, HIV infection of PHA-activated PBMC led to enhanced release of IL-6 into the culture supernatants. Moreover, soluble IL-2R release was markedly increased by adding exogenous IL-6, whereas it was decreased by adding the neutralizing anti-IL-6 mAb to the cultures. These results demonstrate that increased IL-6 levels are significantly associated with sIL-2R levels, and suggest a cause of the increased levels of this receptor in patients with HIV infection. Furthermore, both serum IL-6 and serum IL-2R levels in HIV infection reflect the stage of the HIV-induced disease. PMID- 2258608 TI - Immunodominance in the graft-vs-host disease T cell response to minor histocompatibility antigens. AB - Immunodominance controls the generation of CTL in the C57BL/6By (B6) anti-BALB.B H-2b-matched strain combination. Despite the potential of responding to numerous individual minor histocompatibility (H) Ag on BALB.B APC, the focus of the CTL response is largely specific for only a limited number of target Ag. These minor H Ag could be distinguished by their differential expression on a panel of target cells from the CXB recombinant inbred strains, the E, G, I, J, and K (all H-2b), which express different composites of the original BALB minor H Ag. A hierarchy was observed in which first-order immunodominant Ag were present on both CXBK and CXBG cells, whereas second-order dominant Ag were found on CXBE, CXBJ, and CXBI cells. To test whether immunodominance also plays a role in the development of lethal graft-vs-host disease (GVHD) directed to multiple minor H Ag, B6 T cells were transplanted along with T cell depleted bone marrow, to irradiated (825 rad) recipients of either the BALB.B or CXB recombinant inbred strains. The results indicate that a hierarchy of immunodominance does exist in GVHD, but it differs from that predicted from the in vitro CTL studies. GVHD was observed in BALB.B, CXBE, CXBI, and CXBJ recipients, but not in CXBG and CXBK recipients. Presensitization of B6 donor mice to CXBG or CXBK splenocytes 3 wk before transplant did not significantly increase the overall GVHD potential in the corresponding CXBG or CXBK recipients. Evidence for second-order immunodominance was provided by the transfer of CXBE T cells and ATBM to irradiated CXBG and BALB.B recipients with resultant, potent GVHD. PMID- 2258609 TI - Cardiac myosin-induced myocarditis. Heart autoantibodies are not involved in the induction of the disease. AB - We recently demonstrated that cardiac myosin is capable of inducing autoimmune myocarditis in genetically predisposed mice. This disease parallels coxsackievirus B3-induced autoimmune myocarditis in many respects and is associated with high-titer autoantibodies specific for cardiac myosin. The following lines of evidence suggest that these autoantibodies are not involved in the induction of autoimmune myocarditis: 1) immunoperoxidase staining of heart sections from cardiac myosin-immunized A/J and A.SW mice revealed IgG depositions only along damaged muscle fibres in infiltrated areas, but not in intact tissue; 2) myosin autoantibodies did not bind to the surface of viable cardiac myocytes isolated from mice, but only reacted with myocytes permeabilized with detergent; 3) mice treated with a single high dose of cyclophosphamide, which reduces the humoral immune response, still developed severe myocarditis, despite the fact that their autoantibody titers were reduced to the level of adjuvant-injected controls; and 4) passive transfer of high-titer myosin autoantibodies failed to induce myocarditis, although the titers in the recipients were comparable to those found in mice with cardiac myosin-induced disease. Together, the results suggest that high-titer myosin autoantibodies are secondary rather than primary to the disease. PMID- 2258611 TI - Identification of a soluble IL-2 receptor beta-chain from human lymphoid cell line cells. AB - A clone was isolated from the human lymphoid cell line YT that displayed IL-2R beta, and was found to express much higher levels of IL-2R beta than the original cells. Combining cell surface iodination, affinity labeling of the released soluble protein, and fluorescence sandwich-ELISA for both IL-2 and IL 2.(soluble)(s)IL-2R beta reactants revealed the presence of IL-2-binding protein in the culture supernatant as soluble forms of IL-2R beta. By using the fluorescence sandwich-ELISA elevated levels of sIL-2R beta were measured in culture supernatants of human T cell leukemia virus I positive T cell lines. In addition to this constitutive production of sIL-2R beta, normal PBMC could release low levels of IL-2R beta by stimulation with PHA. In contrast, this was not found in certain human T cell leukemia virus I negative T cell, B cell and macrophage lines. Immunoprecipitation of the soluble protein with IL-2R beta specific mAb characterized it as an apparent 50- to 55-kDa molecule that is distinct from the 45-kDa soluble IL-2R alpha. Moreover, 10 to 15% of the total cell surface molecules were released into culture supernatants. These results suggest that the released IL-2R beta might serve as an immunoregulatory function in IL-2 dependent both normal and abnormal immune responses. PMID- 2258610 TI - Chemoprotective effects of recombinant human IL-1 alpha in cyclophosphamide treated normal and tumor-bearing mice. Protection from acute toxicity, hematologic effects, development of late mortality, and enhanced therapeutic efficacy. AB - In this study, recombinant human IL-1 alpha (rhIL-1 alpha) was used to protect normal and tumor-bearing BALB/c mice from the acute toxicity caused by lethal doses of cyclophosphamide (Cy) and 5-fluorouracil. Pretreatment of mice for 7 days with 10,000 U/day of rhIL-1 alpha protected 70 to 100% of mice from the acute death induced by lethal doses of both Cy (380 mg/kg) and 5-fluorouracil (250 mg/kg). In contrast, post-treatment of mice with single or multiple doses of rhIL-1 alpha was not chemoprotective. Pretreatment of mice with rhIL-1 alpha increased the acute LD90 of Cy from 380 mg/kg to greater than 500 mg/kg in normal mice, an LD90 dose-modifying effect of at least 1.25, was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte, myeloid, or myelomonocytic colonies. Some of the mice (10 to 50%) that were successfully protected by pretreatment with rhIL-1 alpha died after day 50. These mice consistently presented with extensive pulmonary inflammation and fibrosis at death. Mice bearing murine renal cancer (Renca) were also protected from the acute toxic effects of Cy (450 mg/kg) by pretreatment with rhIL-1 alpha. Renca-bearing mice pretreated with rhIL-1 alpha and either sublethal (300 mg/kg) or lethal (450 mg/kg) doses of Cy exhibited enhanced survival times over those of untreated Renca-bearing mice. Interestingly, the cause of death in Renca-bearing mice that ultimately failed treatment with rhIL-1 alpha plus 300 mg/kg Cy was recurrent tumor, whereas most mice treated with rhIL-1 alpha plus 450 mg/kg Cy had no detectable tumor, although several died from late pulmonary inflammation and fibrosis. Thus, the dose escalation of Cy in rhIL-1 alpha-pretreated mice results in greater antitumor effects of Cy. However, the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing. PMID- 2258612 TI - IL-2-dependent proliferation of murine T cells requires expression of both the p55 and p70 subunits of the IL-2 receptor. AB - An IL-4-dependent T cell clone (LD8) was isolated from the murine IL-2-dependent cytotoxic T cell line C30.1. This clone has lost the capacity to proliferate in response to IL-2 after long-term culture in IL-4. LD8 cells express the p70, but not the p55, subunit of the IL-2R on their cell surface. The number of p70 IL-2R molecules on LD8 cells is comparable with the number of high-affinity IL-2R on the parental C30.1 cell line. LD8 cells can efficiently internalize IL-2 through the p70 IL-2R subunit. Following stimulation by IL-2, LD8 cells up-regulate p70 IL-2R mRNA, but do not express p55 IL-2R mRNA. IL-2-dependent proliferation of LD8 cells was reconstituted after introduction and expression of a human p55 IL 2R cDNA. To further investigate the role of p70 IL-2R, we have measured IL-2 induced proliferation of C30.1 cells in the presence of three anti-p55 IL-2R mAb (5A2, PC61, and 7D4) that recognize different epitopes. Under the experimental conditions used, the combination of anti-p55 IL-2R mAb prevents the formation of high-affinity IL-2R, but does not affect the binding of IL-2 to p70 IL-2R or IL-2 internalization. However, these three mAb inhibit proliferation of C30.1 cells even in the presence of IL-2 concentrations sufficient to saturate p70 IL-2R. Together these results demonstrate that p70 IL-2R alone is not sufficient to transmit IL-2-induced growth signals and that formation of p55-p70 IL-2R complex is required for IL-2-dependent proliferation of murine T cells. PMID- 2258613 TI - Analysis of IL-1 and TNF-alpha gene expression in human rheumatoid synoviocytes and normal monocytes by in situ hybridization. AB - Human IL-1 alpha, IL-1 beta, and TNF-alpha mRNA expression was examined in peripheral blood monocytes (PBM) from normal individuals and in primary synoviocytes isolated from patients with rheumatoid arthritis by Northern blot and in situ hybridization. Cells cultured in the presence or absence of LPS were analyzed using in vitro synthesized 35S-labeled sense or antisense RNA probes to determine the relative abundance and the cell type expressing each of the mRNA for these potent inflammatory mediators. The results indicated that 72% of the LPS-stimulated PBM expressed detectable levels of IL-1 alpha mRNA, 89% IL-1 beta mRNA, and 10% TNF-alpha transcripts. Thus, the majority of activated PBM produced both IL-1 alpha and IL-1 beta. Experiments combining immunofluorescence for IL-1 beta protein with in situ hybridization for TNF-alpha mRNA demonstrated that monocytes expressing TNF-alpha mRNA also produced IL-1 beta. Primary synoviocytes from four patients with RA were also examined for the mRNA expression of each cytokine. Northern blot analyses of total RNA isolated from 0 to 72 h after LPS- or mock-stimulation showed that IL-1 beta mRNA was the most abundantly expressed, followed by TNF-alpha. In situ hybridization revealed that IL-1 beta and TNF alpha transcripts were detected exclusively in synovial tissue macrophages. IL-1 alpha mRNA was not detected in these cultures by either method. PMID- 2258614 TI - Lipopolysaccharide-induced modulation of human monocyte urokinase production and activity. AB - Cells of the monocyte/macrophage lineage are known to produce urokinase type plasminogen activator (u-PA) and are active participants in the inflammatory response. Modulation of cellular u-PA production, for instance in response to LPS, may have an important impact on the evolution of inflammatory lesions. A definitive picture of how monocyte u-PA production and activity are regulated by LPS is lacking. We addressed this issue directly by measuring u-PA Ag and activity in mononuclear cell cultures. By using a competition ELISA to quantitate u-PA Ag, we found that LPS-stimulated mononuclear cells in culture increased u-PA production in a dose-dependent manner and that all the u-PA detected was attributable to the monocytes therein. Increasing amounts of u-PA were secreted into the medium, bound to the cell surface, and found intracellularly. Although the absolute amounts of u-PA varied from donor to donor, the increases seen with LPS stimulation were a consistent and statistically significant finding. Only the cell-surface-bound u-PA was fibrinolytically active, however, with this activity increasing upon LPS stimulation. All monocyte cell-surface-associated fibrinolytic activity was attributed to u-PA, as shown by plasminogen dependence, neutralization by antibodies to u-PA, and identification of fibrinolytically active molecules eluted from the cell surface. The surface bound u-PA was not inhibited by its physiologic inhibitors, PAI-1 or PAI-2, whereas free u-PA was. Hence LPS stimulation results in monocytes exhibiting increased cell-surface associated u-PA Ag and fibrinolytic activity, in spite of concomitant high levels of plasminogen activator inhibitor type 2 production. This surface-bound enzymatic activity may influence the ability of monocytes to migrate in and interact with an inflammatory microenvironment. PMID- 2258616 TI - Androgen regulation of secretory component synthesis by lacrimal gland acinar cells in vitro. AB - This study sought to determine whether androgens directly stimulate the production of secretory component (SC) by acinar cells from the rat lacrimal gland. Homogeneous populations of acrinar cells were isolated from lacrimal tissues by serial enzymatic digestion and Ficoll gradient centrifugation and then cultured on reconstituted basement membranes in supplemented, serum-free medium. Acinar cell exposure in vitro to dihydrotestosterone (DHT) resulted in a significant increase in cellular SC output. This hormone action was dose dependent and androgen specific. Testosterone, but not 17 beta-estradiol, progesterone, dexamethasone, or aldosterone, also induced a considerable elevation in acinar cell SC production. The effect of testosterone may not require intracellular enzymatic conversion to DHT. The impact of androgens on SC output was associated with enhanced cellular synthesis and secretion and did not involve variations in acinar cell viability or density. Moreover, the SC response to DHT occurred irrespective of whether lacrimal gland acinar cells were obtained from young adult male or female rats. In contrast, the androgen-related rise in SC production was significantly reduced in acinar cells isolated from tissue of orchiectomized and hypophysectomized rats. In summary, these findings demonstrate that androgens directly increase the synthesis of SC by lacrimal gland acinar cells in vitro. This effect, however, may be significantly altered by prior changes in the endocrine environment of acinar cells in vivo. PMID- 2258615 TI - Human and murine anti-DNA antibodies induce the production of anti-idiotypic antibodies with autoantigen-binding properties (epibodies) through immune-network interactions. AB - To examine the potential role of immune-network interactions in the production of lupus autoantibodies, normal NZW rabbit antibody responses were analyzed after immunization with one of the following Ig preparations: human lupus serum anti dsDNA antibodies, human lupus serum anti-ssDNA antibodies, a mixture of human lupus serum anti-dsDNA and anti-ssDNA antibodies, the MRL-lpr/lpr anti-dsDNA mAb H241, and the MRL-lpr/lpr anti-ssDNA mAb H130. Four of five rabbits produced Ig typical of lupus autoantibodies: individual rabbit Ig cross-reacted with multiple autoantigens including nucleic acids, cardiolipin, SmRNP, glomerular extract, laminin, and exogenous Ag. Rabbit anti-Id against human anti-dsDNA antibodies were highly specific for dsDNA. Notably, in each serum the autoantibody activity was confined to the anti-Id Ig fraction. A similar spontaneously occurring Id anti-Id interaction was also found between anti-ssDNA and anti-dsDNA antibodies isolated from an individual lupus patient. These results indicate that lupus autoantibodies which share Ag binding properties with pathogenic Ig, including both cross-reactive and anti-dsDNA antibodies, can induce the production of Ig with similar autoantigen binding properties through immune-network interactions. This phenomenon, if unregulated, could lead to the amplification of pathogenic autoantibody production in individuals with systemic lupus. PMID- 2258617 TI - Staphylococcus aureus infection of human endothelial cells potentiates Fc receptor expression. AB - Vasculitis, a recognized complication of staphylococcal-endovascular infections, may result in part, from the expression of FcR by Staphylococcus aureus-infected endothelial cells. FcR were measured using [51]Cr labeled SRBC preincubated with rabbit anti-SRBC IgG. FcR were not detected on uninfected endothelial cells, but were demonstrated on S. aureus infected cells using IgG, but not IgM labeled SRBC. FcR expression was dependent on the initial bacterial density (greater than or equal to 8 x 10(7) cfu/ml) and on phagocytosis of the staphylococci, but not on new protein synthesis. IgG labeled SRBC binding was blocked by aggregated IgG but not IgM. SRBC coated with the F(ab')2 portion of IgG did not bind, thus confirming that FcR were specifically involved in this interaction. FcR are expressed after S. aureus invasion of human endothelial cells and may contribute to the vasculitis which often accompanies S. aureus-endovascular infections. PMID- 2258618 TI - Filarial-specific IgG4 response correlates with active Wuchereria bancrofti infection. AB - The filarial-specific humoral immune response of adult residents of two areas of Papua New Guinea, differing in transmission of Wuchereria bancrofti infection was compared. The majority of residents of the village of Bonahoi, in an area where transmission of filariasis had been interrupted by a 20-year insecticide spray program to control malaria, showed no parasitologic signs of active W. bancrofti infection and were negative for both circulating phosphorylcholine Ag and peripheral blood microfilariae. In contrast, adult residents of the village of Nanaha were in an area exposed to infection, and were phosphorylcholine-Ag- and microfilariae-positive. The antibody response of these two groups to both adult worm excretory/secretory (ES) Ag and somatic antigen extract was examined to determine which components of the filarial-specific immune response were dependent on active infection. Identification of these immune responses may point to immunologic methods to evaluate control programs for lymphatic filariasis. Adults from Bonahoi were found to have significant immune responses to [35S] methionine-labeled ES Ag by immunoprecipitation and to adult somatic antigen extracts by ELISA and by immunoblotting. This result is consistent with the fact that these individuals were previously exposed to and/or infected with W. bancrofti. Similarly, residents of the endemic village had detectable immune responses to these Ag irrespective of if they were microfilaremic. The most striking immunologic difference observed between the two groups was that residents of Bonahoi had a dramatically reduced filarial-specific IgG4 antibody response to both adult somatic Ag and adult ES Ag. These data suggest that longitudinal measurement of filarial-specific IgG4 levels may be a useful seroepidemiologic indicator of changes in W. bancrofti infection status. PMID- 2258620 TI - Identification and analysis of cDNA clones encoding CD53. A pan-leukocyte antigen related to membrane transport proteins. AB - CD53 is a human cell-surface Ag expressed exclusively by nucleated cells of hemopoietic origin. In this work a cDNA clone encoding the CD53 Ag was isolated from a COS cell-expression library. The sequence of the cDNA predicts a protein of 219 residues bearing four putative membrane-spanning hydrophobic domains. Sequence analysis shows that CD53 is related to three other recently described molecules: a melanoma Ag, ME491; a B cell Ag, CD37; and the broadly distributed hemopoietic cell Ag S5.7. Comparison of NH2-terminal protein sequence of OX44 rat Ag and CD53 suggest that CD53 is the human homologue of OX44. In addition, CD53 is distantly related to Escherichia coli lac Y permease, a type III integral membrane protein that ferries lactose into the bacterial cell. CD53 transcripts increase in prevalence after mitogenic stimulation, suggesting that the protein may be involved in the transport of factors essential for cell proliferation. PMID- 2258619 TI - Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. AB - Hybrid HBV nucleocapsid-pre-S(2) fusion proteins were stably expressed in several aromatic-dependent attenuated Salmonella typhimurium and Salmonella dublin strains. When these live recombinant bacteria were administered i.p. to BALB/c mice they induced high titer anti-hepatitis B virus core Ag (HBc) and detectable anti-pre-S2 serum antibodies. Upon oral feeding of the recombinant salmonellae to mice, the rate of seroconversion to anti-HBc was dependent on the salmonella strain used. With the best carrier strain high titer anti-HBc antibodies and lower titer anti-pre-S2 serum IgG antibodies were observed two weeks after a single oral immunization. The Ig class and IgG subclass distribution of anti-HBc antibodies after i.p. and oral immunization is consistent with the induction of functional T cell help. PMID- 2258621 TI - Glucocorticoid-regulated gene expression in the immune system. Analysis of glucocorticoid-regulated transcripts from the mouse macrophage-like cell line P388D1. AB - To further elucidate the molecular mechanisms underlying glucocorticoid-mediated immune suppression, we have exploited cDNA cloning and subtractive screening methods to identify glucocorticoid-regulated transcripts in the mouse macrophage like cell line, P388D1. Two of the three isolated glucocorticoid-regulated mRNA species corresponded to genes potentially important to immunoregulation: one glucocorticoid-suppressed mRNA species probably encoded the previously uncloned 3 hydroxy-3-methylglutaryl coenzyme A reductase, an enzyme that appears important for in vitro immune responses. The other mRNA species showed glucocorticoid increased mRNA steady-state levels and was transcribed from an endogenous ecotropic type C retroviral locus. This transcript gives rise to a protein (transmembrane retroviral protein, formerly p15E), which, along with its feline and human homologs, has been implicated in immunosuppression caused by mouse, cat, and human retroviruses. Our results raise the possibility that the immunosuppressive activity of glucocorticoids might be mediated, in part, by regulating the expression of the above immunoregulatory proteins. PMID- 2258622 TI - Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. AB - Autoantibodies to a novel nuclear Ag, Sp100, have recently been described that recognize a nuclear protein with an apparent molecular mass of 95 to 100 kDa and a dot-like distribution within cell nuclei. By immunoscreening of a lambda gt11 cDNA expression library derived from HeLa cells with an anti-Sp100 autoimmune serum a 0.7-kb cDNA (Sp26) coding for a fragment of Sp100 was isolated. Expression of this cDNA and use of the recombinant protein in ELISA revealed that the fragment carries major Sp100 autoepitopes and that anti-Sp100 autoantibodies predominantly occur in patients suffering from primary biliary cirrhosis (50/184). The Sp26 cDNA was used as hybridization probe for isolation of longer cDNA from human liver- and placenta-derived lambda gt10 cDNA libraries. Overlapping fragments were assembled to generate a full length cDNA coding for a protein with a molecular mass of 53 kDa and an isoelectric point of 4.7. The Sp100 autoantigen expressed in vitro from this cDNA and authenticated by a capture immunoblot assay, comigrated in SDS-PAGE with the authentic HeLa autoantigen of 95 to 100 kDa and thus showed an aberrant electrophoretic mobility. Computer based protein sequence analysis of the Sp100 autoantigen revealed regions of striking sequence similarities to the alpha 1 and alpha 2 domains of various human and non-human MHC class I Ag and to several transacting transcriptional regulatory proteins. PMID- 2258624 TI - Evidence for an epidermal cytokine network. AB - Cytokines are (glyco)proteins that are synthesized and secreted by various cells, which bind to specific receptors on target cells and which regulate activation, proliferation, and differentiation of immune as well as non-immune cells. Keratinocytes upon injury release interleukin (IL)-1, IL-6, IL-8, colony stimulating factors, and tumor-necrosis factor, as well as growth and suppressor factors. There is also strong evidence for a network of interacting cytokines, which has been only partially characterized so far, maintaining a proper balance. However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those with infectious and autoimmune genesis. Therefore the understanding of cytokine interactions may be helpful in elucidating the pathomechanisms of such diseases. Moreover, certain cytokines, as well as their analogues and antagonists, may prove to be of therapeutic value. PMID- 2258623 TI - Differences in transcriptional enhancers of HIV-1 and HIV-2. Response to T cell activation signals. AB - T cell activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection. In HIV-1, the sequences that respond to these signaling events are found in the long terminal repeat (LTR) and comprise the transcriptional enhancer, which contains two conserved binding sites for the nuclear factor kappa B (NF kappa B). The corresponding region in the second AIDS retrovirus, HIV-2, contains a conserved and a divergent NF kappa B binding site. We demonstrate that the HIV-1 LTR responds better than the HIV-2 LTR to T cell activation signals. These qualitative differences in the response to T cell activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a heterologous promoter but also when these enhancers are switched between their respective LTR. In electrophoretic mobility shift assays, NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer. Instead of NF kappa B, the activator protein 3 binds to the divergent site in HIV-2. In conclusion, HIV-1 and HIV-2 are differentially regulated by T cell activation signals, and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV 1 infection. PMID- 2258625 TI - The role of keratinocyte cytokines in inflammation and immunity. PMID- 2258626 TI - Leukocyte chemoattractant cytokines of the epidermis. AB - The constitutive production of interleukin-1 alpha-like material in normal human epidermis, its inflammatory properties, and the mechanism of its inflammatory action are briefly reviewed. The isolation of interleukin-8 from psoriatic lesions, its in vitro production, and leukocyte chemoattractant properties are also described. Available evidence suggests that interleukins-1 and -8 are inflammatory cytokines of major potential importance in the induction of leukocyte infiltrates in human skin. PMID- 2258627 TI - Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. AB - Immunologic cytotoxicity is an important endpoint of the immune response to tumors, viral infected cells, grafted tissues, and exogenous microorganisms, and is also an important mechanism of disease, especially in autoimmunity. There are multiple mechanisms of immunologic cytotoxicity, but each has three major stages: leukocyte/target attachment, specific recognition, and target lysis following effector activation. Adhesion molecules present on leukocytes and potential targets appear to be involved in all three stages of cytotoxicity. A major factor in all types of cellular cytotoxicity is the interaction of LFA-1 on leukocytes and CAM-1 on targets. Modulation of ICAM-1 levels on target by the cytokines TFN g, IL-1, and TNF-a is a major point of control of the susceptibility of targets to cytotoxicity by many different cytotoxic mechanisms. It also appears that modulation of the avidity of LFA/ICAM-1 binding is another important control point in modulating immunologic cytotoxicity. Cytokines also have important effects on immunologic cytotoxicity in ways other than adhesion molecule induction: effector priming to better respond to specific recognition signals, effector mobilization into tissue, and expansion of cytotoxic effector populations. ICAM-1 on the surface of epidermal keratinocytes and melanocytes is likely to greatly influence cytotoxic damage of these cells in diseases as photosensitive lupus erythematosus, lichen planus, erythema multiforme, and vitiligo. It has been found that the epidermal staining pattern for ICAM-1 in each of these diseases in distinctive and different in each disease. It is proposed that disease-specific induction of ICAM-1 by factors such as UVR and herpes-virus is an important determinant in triggering these skin diseases and in determining the pattern of disease. PMID- 2258628 TI - Interleukin-1 and interleukin-6 in psoriasis. AB - We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients. Different approaches were pursued. Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay. Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies. Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin. Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta. Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable. Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients. In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced "dot-like" intracellular staining pattern was observed. On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions. Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line. Very low levels of IL 6 mRNA were expressed in KC from psoriasis lesions and healthy individuals. Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA. The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL 1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells. This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales. Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA. dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo. PMID- 2258630 TI - Abnormal cutaneous topobiology: the molecular basis for dermatopathologic mononuclear cell patterns in inflammatory skin disease. AB - Because of the identification and characterization of various adhesion molecules (lymphocyte function associated antigen-1, intercellular adhesion molecule-1), chemotactic factors (interleukin-8, monocyte chemotactic/activating factor), and their modulatory cytokines (gamma interferon, tumor necrosis factor), it is possible to begin to ascribe specific molecules to cutaneous cellular reaction patterns. The abnormal topobiology, or altered spatial distribution, of mononuclear cells, which gives rise to disease-specific patterns, was described in molecular terms. A large number of diverse skin diseases were classified into six different groups, with each group highlighting distinctive cell types, adhesion molecules, chemotactic factors, and cytokines. The diseases within each group, which share functional anatomical reaction zones, were postulated to share common pathophysiologic pathways. Thus, it is now possible, as one scans the microscopic field, to look past the static images of red- and blue-stained cells and appreciate a dynamic and detailed medley of molecularly defined events emanating from the eyepiece. PMID- 2258629 TI - A possible role for transforming growth factor-beta in systemic sclerosis. AB - The cause of systemic sclerosis remains unknown, but cellular and molecular mechanisms possibly responsible for the characteristic clinical manifestations of fibrosis and vascular damage (Raynaud's phenomenon, telangiectasis, digital infection, and renal arteriopathy) are becoming understood in greater detail. One possibly important cytokine is transforming growth factor-beta (TGF-beta); its involvement is reviewed here. With regard to vascular lesions, TGF-beta has variably been shown to inhibit endothelial cell growth in vitro but to promote angiogenesis in vivo, a paradox that remains unresolved. Nonetheless, an injurious activity of TGF-beta on microvascular endothelial cells could help to explain the intimal proliferation and microvascular obliteration seen. Whether as a result of or as a cause of endothelial cell damage, platelet activation has been well documented in systemic sclerosis and the platelet alpha granule pool contains a large quantity of TGF-beta. TGF-beta is also produced by activated macrophages and T cells, both of which are known to occur within systemic sclerosis lesions. An important effect of TGF-beta is its stimulation of fibroblast collagen and fibronectin synthesis and their deposition into the extracellular matrix. Stimulation by TGF-beta may therefore account for the fibrosis seen in the dermis and in the internal organs. Direct evidence of TGF beta involvement in systemic sclerosis is scanty, and awaits discovery of either an abnormal expression of or response to TGF-beta. The biologic effects of TGF beta appear to be regulated at the level of activation from a latent polypeptide precursor form. Descriptions of the importance of this cytokine in pathologic conditions will need to account for this activation and its regulation. Nonetheless, the physiologic effects so far attributed to TGF-beta make its involvement in systemic sclerosis an attractive possibility to explain some of the manifestations of this enigmatic disease. PMID- 2258631 TI - Response of discoid and subacute cutaneous lupus erythematosus to recombinant interferon alpha 2a. AB - Ten patients suffering from discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) were treated with interferon alpha 2a. A marked improvement or clearing of cutaneous lupus erythematosus lesions was observed in eight of them. However, the response to interferon was of short duration and within a few weeks after interferon withdrawal all patients who were improved or cleared relapsed. This study suggests that interferon alpha 2a represents a new interesting approach in the treatment of DLE and SCLE. Ongoing trials will define the optimal treatment schedule for the maintenance of interferon-induced improvement of cutaneous lupus erythematosus. PMID- 2258632 TI - Application of beta-interferon in virus-induced papillomas. AB - Eighty patients with bilateral common warts of the extremities were treated at weekly intervals with intralesional injections of either human fibroblast interferon or placebo. Lyophilized interferon (3 X 10(6) units) was diluted with 3 ml of normal sterile saline matched with identical vials of placebo. Eighty sets of three vials of human fibroblast interferon or placebo were labeled either A or B by a controller who maintained the code until the experiment was completed. Each patient received 0.1 X 10(6) units of interferon into the warts on one side and placebo injections into those on the matching extremity. Warts were measured each week and the progress or lack thereof was scored on a scale of -1 (worse) to 3 (cured). Therapy continued until either at least one extremity had cleared or the patient had received 10 weekly injections. A final evaluation was scored by measuring the total progress of each patient during the study. Sixty-four patients were treated to completion. More than 81% of the interferon treated extremities were either cured or responded effectively to therapy. Only 17% of the placebo-treated lesions responded in this fashion. A statistical analysis of these data confirms the effectiveness of intralesional interferon therapy. The average number of interferon injections until cure was 5.9 +/- 1.7. No adverse effects were observed. The applications of interferon in patients with epidermodysplasia verruciformis and flat warts were also studied. Intralesional interferon beta was, to a certain degree, effective for benign lesions of epidermodysplasia verruciformis, but systemic treatments were not effective. Subcutaneous interferon beta was, in an uncontrolled study, effective in 45% of patients with flat warts. PMID- 2258633 TI - Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects. AB - Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients. Moreover, both drugs have demonstrated an inhibitory effect on HIV replication. Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy. Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d. Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia. Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months). The dosage was reduced as required based on drug-induced cytotoxicity. Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%. Negative p24 expression prior to treatment was a positive predictor. Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively. In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients. In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment. PMID- 2258634 TI - Non-AIDS-associated Kaposi's sarcoma (classical and endemic African types): treatment with low doses of recombinant interferon-alpha. AB - In the treatment of the classical and endemic African forms of Kaposi's sarcoma (KS), radiation therapy and chemotherapy have been widely used with varying degrees of success and morbidity. We here report our preliminary experiences with low doses of recombinant interferon alfa-2b (rIFN alpha-2b) in the treatment of these types of KS, non-linked to the acquired immunodeficiency syndrome (AIDS). Ten consecutive patients (eight patients with classical and two with endemic KS) with a median age of 62 years were treated long-term with 5 X 10(6) units of rIFN alpha-2b (Introna) given subcutaneously three times weekly for at least 6 months. Of the 10 patients, six presented with cutaneous disease only, and four had additional visceral involvement. After 6 months of treatment, seven of the 10 patients had a major response of the cutaneous lesions, and three patients showed stable skin diseases. Of the four patients with additional visceral disease, one patient showed a complete regression of an intramyocardial tumor involving the right atrium and ventricle, whereas in the three other patients stabilization of the visceral lesions with marked symptomatic improvement occurred. On the whole, the long-term results over a median duration of 12 months (range, 7 to 30) are also satisfactory: IFN-alpha continued to control KS in all patients. The treatment was generally well tolerated; no serious side effects were observed. Our preliminary data suggest that low-dose rIFN alpha-2b regimens are effective in classical and endemic African KS. However, further studies are needed to establish the exact role for IFN-alpha as alternative to radiation and chemotherapy. PMID- 2258635 TI - Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b. AB - Fifty-three high-risk melanoma patients in stage I and 15 patients in stage II were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha-2b (rIFN alpha 2b) therapy for a total period of 20 months. Concomitant patients (stage I, n = 82; stage II, n = 33) with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rIFN alpha 2b therapy. No difference in 5-year relapse incidence and overall survival rates could be detected. However, it appears that patients of both stage I and stage II benefit from long-term adjuvant rIFN alpha 2b therapy, because during the treatment period (20 months), the incidence of relapses was lower in comparison to controls. After stopping treatment the incidence of relapse is equal in treated and control groups. According to the results of our study, we suggest using continuous low-dose rIFN alpha 2b therapy for adjuvant treatment of malignant melanoma. PMID- 2258636 TI - Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma. AB - Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas. PMID- 2258637 TI - Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma. AB - Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone. Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission. Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects. Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly. Etretinate (0.7 mg/kg) was given orally. The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma. PMID- 2258638 TI - TNF alpha primes polymorphonuclear leukocytes for an enhanced respiratory burst to a similar extent as bacterial lipopolysaccharide. AB - We examined whether preincubating polymorphonuclear leukocytes (PMN) with TNF alpha would result in an enhanced respiratory burst upon subsequent stimulation by various agents. Bacterial lipopolysaccharide (LPS), a known primer of PMN, was used as control. We found that both LPS (0.01 to 10.0 microgram/ml) and recombinant TNF alpha (0.001 to 1.0 microgram/ml) act as direct stimulants of PMN as measured by chemiluminescence. Sixty minutes of preincubation of PMN with 1 microgram/ml TNF alpha or 10 micrograms/ml LPS resulted in similar priming for the respiratory burst elicited by opsonized zymosan, phorbol myristate acetate, zymosan, zymosan-activated serum, aggregated immunoglobulin, and f-met-leu-phe (FMLP) depending on the method of measurement used, i.e., chemiluminescence, production of O2-, and H2O2. Priming with TNF alpha for an enhanced response to stimulation by FMLP could be abrogated by anti-TNF alpha antibody. Cell-surface receptor numbers and binding-affinity constants for FMLP remained stable under conditions leading to priming. We conclude that TNF alpha is able to prime PMN for an enhanced respiratory burst to a similar extent as with LPS. Because PMN cell-surface receptors for FMLP are unaltered by priming, the enhanced respiratory burst seems to be due to changes in intracellular metabolism. PMID- 2258639 TI - Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy. AB - Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10 10,000 U/ml rTNF-alpha applied for 72 h. The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments. The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE. Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha. In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment. On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant. The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment. Overall, rTNF alpha enhanced the malignant immunophenotype of the cell lines tested. It increased the expression of the "late" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the "early" progression marker K.1.2. The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines. These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells. These effects may result in selection of rTNF-alpha-non-sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro. PMID- 2258640 TI - Interferons and collagen production. AB - The immunoregulatory, antiviral, and antiproliferative agents known as the interferons have profound effects on collagen synthesis. Interferons alpha, beta, and gamma suppress collagen synthesis by dermal fibroblasts. In addition, interferon gamma (IFN-gamma) inhibits the constitutively increased collagen synthesis characteristic of fibroblasts derived from lesions of patients with scleroderma. IFN-gamma also inhibits collagen synthesis by myofibroblasts and synovial fibroblast-like cells. Inhibition of collagen synthesis by IFN-gamma is associated with a coordinate inhibition of transcription for types I and III collagen. In addition, IFN-gamma suppresses levels of procollagen mRNA and type II collagen synthesis in human articular chondrocytes. In vivo studies in mice have demonstrated that IFN-gamma inhibits the collagen synthesis associated with the fibrotic response to an implanted foreign body, bleomycin-induced pulmonary fibrosis, and the healing response to cutaneous thermal burns. In the latter case, while collagen content of the wound scar was decreased, hyaluronic acid was increased in mice receiving IFN-gamma compared to controls. This is in accord with in vitro studies showing that, while interferons alpha and beta decrease production of glycosaminoglycans, IFN-gamma increases production of glycosaminoglycans. Of interest, acute inflammation at sites of thermal injury, or when elicited by proinflammatory agents in separate experiments, also was suppressed in mice treated with IFN-gamma. The means by which IFN-gamma inhibits collagen synthesis involves transcriptional regulation. There is a single report that interferon alpha can decrease the size of a keloid of recent onset in a human patient. Because the interferons can inhibit collagen synthesis in vivo, further studies may be warranted to evaluate the usefulness of these agents in the treatment of disease states characterized by abnormal fibrotic responses as well as their potential for altering the healing response associated with particular therapeutic interventions. PMID- 2258641 TI - Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. AB - Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states. PMID- 2258642 TI - [ELISA for type-specific group B streptococcal antibody and its clinical significance]. AB - In order to investigate the neonatal infection of group B streptococci (GBS), vaginal and anal cultures, and measurement of type-specific antibodies to GBS were carried out on 461 pregnant women. Levels of antibody to GBS were measured with ELISA plates coated with type-specific antigen of GBS. These plates were furnished by Toyo Jozo Co., Ltd. The results were as follows: 1) Antibodies to type Ia, Ib, II and III were detected in 41.9, 34.7, 31.7 and 40.1% of subjects, respectively. 2) GBS was isolated in 78 (16.9%) of subjects. 3) Antibody levels against GBS in the sera of colonized mothers and cord blood of their infants were well correlated. 4) Among the colonized mothers, 4 out of 19 (Ia), 9 out of 18 (Ib) 5 out of 8 (II) and 5 out of 17 (III) showed low levels of antibody. 5) Those who had low levels of antibody were administered antibiotic delivery, and there was no case of crisis in both treatment (antibody levels were negative) and non-treatment (antibody levels were positive) groups. PMID- 2258643 TI - [Epidemiological study of group C rotavirus]. AB - By electron microscopy survey of acute gastroenteritis of children in Matsuyama, rotaviruses were detected in 561 of 2479 fecal samples obtained between October, 1984 and September, 1988, in which 60 atypical and 259 typical rotaviruses, so far tested, were detected by polyacrylamide gel electrophoresis (PAGE) of viral RNA. Out of 60 atypical rotaviruses, 5 were observed in 1985, 7 in 1986, none in 1987 and 48 in 1988. These atypical rotaviruses were morphologically indistinguishable from typical ones and showed very similar RNA migration patterns of PAGE to those of group C rotavirus. Furthermore, one atypical virus (86-542) reacted with antiserum against a porcine group C rotavirus in immune electron microscopy, while it did not react with anti-group A rotavirus serum. On the other hand, hyperimmune guinea pig antiserum against 86-542 reacted with a couple of atypical rotavirus including viruses isolated in 1988, so far tested, but did not react with any of the typical viruses. These findings showed that atypical rotaviruses which were endemic in Matsuyama city in 1988 were defined as group C rotavirus. Moreover, these group C rotaviruses showed two kind of RNA migration patterns in PAGE, which clearly discriminated the virus were isolated before and after 1987. Epidemiological features of group C rotavirus were as follows. Children from whom group C rotavirus was isolated were older than those from of whom group A rotavirus was isolated. The epidemic season was in February through April, compared to December through March in group A virus. Retrospective seroepidemiological study by immune adherence hemagglutination test (IAHA) using the purified 86-542 virus as antigen indicated that 15 of 78 sera of children obtained in 1971 already possessed IAHA antibody against group C rotavirus. PMID- 2258644 TI - [Isolation of methicillin-resistant Staphylococcus aureus (MRSA) at the Hokusho Central Hospital--observation during the recent 4 years]. AB - Clinical and bacteriological studies were carried out to investigate the isolation of MRSA from clinical materials, during the 4 years from 1985 to 1988 at the Hokusho Central Hospital. The isolation frequency of MRSA from Staphylococcus aureus increased from 5.6% (3 strains) in 1985 to 50.0% (90 strains) in 1988. MRSA from sputum and pressure sore increased significantly. However MRSA from outpatient and inpatient in the ward for common people were constant, about 20%. Inpatients in the ward for aged person were increased significantly from 13.6% (3 strains) to 67.0% (67 strains). Most of the patients with positive MRSA isolation had background diseases (88.3%) and were bedridden (78.4%). Patients with cerebrovascular disease were 55.9% of all of the cases. But most of the MRSA strains were resistant to CZX, FOM, DMPPC, CMX, CEZ, CZON, CZX, most of the MRSA strains were sensitive to RFP, VCM, MINO, IPM/CS. PMID- 2258645 TI - [Asporogenic anaerobic empyema--clinical and bacteriological investigations of 31 patients with anaerobic empyema]. AB - The author reviewed the records of 31 patients with asporogenic anaerobic empyema mostly seen in the wards of Internal Medicine, Juntendo University Hospital during the 27 years between 1961 and 1988, and obtained the following results. 1. There were 25 males and 8 females with an average age of 57.8 and 51.0 y/o (range, 25 to 79 y/o), respectively males more than forty years old occupied 74.2 percent of all cases. 28 patients (90%) had underlying conditions. 2. The cases of mixed infections with anaerobes and aerobes were only 22.6%. 3. The isolated bacteria were microaerophilic streptococcus, Bacteroides spp., Peptostreptococcus spp., Fusobacterium spp. etc. in this order. 4. There were no relationships between anaerobic infections with or without aerobes and putrid odor of pleural effusion. 5. Bacteroides spp. were isolated most in the group with putrid pleural effusion, however, they were not isolated in the group without putrid pleural effusion at all. This fact suggests that there is an intimate relationship between putrid odor and Bacteroides spp. 6. There was no deceased case which pleural effusion had been drained sufficiently with open or closed drainage. It suggests that sufficient drainage is the most important in therapeutic procedures of asporogenic anaerobic empyema. PMID- 2258646 TI - [Virological studies of the virus shedding pattern of natural measles]. AB - Using a novel, highly sensitive cell culture system, B95a cells, I investigated the virus shedding of measles virus (MV) of 47 cases with natural measles. MV was isolated from both peripheral blood leukocytes and respiratory secretions up to 6 days from the onset of the rash. By fractionation of blood, MV was isolated from lymphocytes and monocytes up to 6 days from the onset of the rash, however it disappeared rapidly within 48 hours from the plasma. The duration of positive MV isolation depends on the duration of fever, i.e. infectious MV could not be recovered beyond the 24 hours after the alleviation of fever. The data suggest that in natural measles, infectious MV is shed for a longer period than previously believed. The role of infection of monocyte in the pathogenesis of measles is also suggested. PMID- 2258647 TI - [Study of serological diagnosis in ocular chlamydial infection with IPAZYME]. AB - We employed a indirect immunoperoxidase assay (IPAZYME in the evaluation of IgG and IgA antibody for Chlamydia trachomatis in serum samples from 218 patients such as cicatricial trachoma 55 cases, culture-positive adult inclusion conjunctivitis 48 cases and culture-negative conjunctivitis 47 cases, aged people, 68 cases as controls respectively. Frequency of positive IgG antibody showed a significant difference between adult inclusion conjunctivitis or cicatricial trachoma and controls. IgA antibody was positive in 25/48 (52%) in adult inclusion conjunctivitis and in 7/55 (12%) in cicatricial trachoma cases. Serum IgA antibody against Chlamydia trachomatis is of value to be an index of active ocular chlamydial inflammation. The correlation between severity of conjunctival cicatrix or corneal punnus and titers of IgG antibody was also significant. PMID- 2258648 TI - [Detection of toxigenic Vibrio cholerae O1 using polymerase chain reaction for amplifying the cholera enterotoxin gene]. AB - A rapid and simple procedure using polymerase chain reaction (PCR) was developed for the detection of cholera enterotoxin (CT) producing character. This method is based on amplifying a 380 base pair (bp) segment of the CT gene (ctx) which controls the production of CT. Two single-stranded oligonucleotides, synthetized to be complementary to the known nucleotide sequences of genes encoding the A subunit of ctx, were used as extension primers. The oligonucleotide sequences are 5'TCAAACTATATTGTCTGGTC (CT-1) and 5'CGCAAGTATTACTCATCGA (CT-2). As template DNA was used 5 microliter of boiled bacterial culture broth at 95 degrees C for 5 min without the need for DNA extraction. The amplified target DNA were confirmed with only CT producing Vibrio cholerae O1 but not with CT non-producing organisms such as heat labile enterotoxin producing Escherichia coli by electrophoretic analysis of PCR mixture after amplification. A few isolates of CT producing V. mimicus and V. cholerae non-O1 were identified. PMID- 2258649 TI - [Development and testing of cholera enterotoxin gene probe for detection of toxigenic Vibrio cholerae O1]. AB - A DNA probe was developed for the genetic detection from cholera enterotoxin (CT) producing Vibrio cholerae O1 and other organisms. The structural genes of CT (ctx) were cloned from chromosomal DNA of CT producing V. cholerae O1 569B. We subcloned a 552-base-pair fragment encoding a part of CT A-subunit for use of the CT-probe, and made the recombinant plasmid called pSKM24 which has eight copies of the CT-probe. The 32P-labeled CT-probe detected ctx in 72 isolates such as V. cholerae O1, V. cholerae non-O1 and other species of bacteria, but did not react heat-labile enterotoxin genes in enterotoxigenic Escherichia coli (ETEC) by DNA hybridization. The colony hybridization test using the CT-probe is specific, rapid and useful technique for detection of ctx and identification of CT producing V. cholerae. PMID- 2258650 TI - [Evaluation of recovery methods of Shigella species from fresh marine fish and shellfishes]. AB - Recovery experiments of Shigella strains from fresh marine fish and shellfishes, including fresh sea urchin, which have been artificially contaminated with the strains, were performed using the improved Shigella broth-enrichment method and the culture method reported by Mehlman et al. All of the 43 Shigella stock cultures strains tested were recovered easily by the enrichment method from sea urchin individuals inoculated with a small number of viable cells of each strain. That is, a total of 24 strains (56%) were recovered from sea urchin individuals inoculated with less than 10 viable cells per one individual, and the other 19 strains were also recovered when 10 to 1,000 cells of each strain were inoculated. Recovery of Shigella strains from fish and shellfishes by the enrichment method was hardly affected by the number of contaminated bacteria (SPC, standard plate counts) in these materials. In order to confirm reliability of the enrichment method, similar experiments were performed using S. flexneri strain B as the inoculum and more fish and shellfishes as the samples (24 specimens of fresh sea urchins, 11 specimens of fresh oysters and 5 other specimens including prawns). Except for one oyster specimen which showed an especially high SPC value, the inoculum was able to be recovered from most of the materials inoculated with less than 10 viable cells, and all of the tested samples became Shigella positive when they were inoculated with up to 1,000 viable cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258651 TI - [Estimate of aztreonam (AZT) hydrolyzing enzymes from clinically isolated AZT resistant gram-negative bacilli]. AB - The MICs of Aztreonam (AZT) against 590 clinical isolates of Gram-negative bacilli were determined. About 13.4% (79 strains) of the isolates were AZT resistant (MIC; 12.5 micrograms/ml less than or equal to). The resistance pattern against various beta-lactams and the effects on MICs of combination of Clavulanic acid (CVA) and AZT against AZT resistant strains suggested that AZT was inactivated by either type of IV (K1), Va (OXA1), or PSE2 beta-lactamases. PMID- 2258652 TI - [Production and characterization of a monoclonal antibody specific for Salmonella O19-antigen]. AB - A monoclonal antibody, SBY1 (IgM, kappa), against the Salmonella O-antigen was generated by using the myeloma cell line Sp2/O-Ag14 as a fusion partner with spleen cells from BALB/c mice immunized with S. senftenberg 963 K. SBY1 was characterized by the slide agglutination and absorption test. SBY1 was believed to show the specificity to O1-, O3- or O19-antigens of Salmonella because S. Senftenberg 963 K (O1, 3, 19) was used as the antigen for immunization. The slide agglutination test with the Salmonella serovars indicated the responsiveness of SBY1. SBY1 was reactive only with strains that possessed O19-antigen. The agglutinating ability of SBY1 was absorbed completely with bacilli possessing O19 antigen. These finding indicates that SBY1 is specific for O19-antigen. Polyclonal factor sera for he serotyping of the O3, 10 group of Salmonella cross reacted with Salmonella group O1, 3, 19 in the slide agglutination test. In contrast, SBY1 did not cross-react with serovars from several other Salmonella groups. These data suggest the usefulness of SBY1 as a serodiagnostic tool for serotyping of Salmonella. PMID- 2258653 TI - [Typhoid fever with intestinal hemorrhage, drug-induced fever, DIC, ARDS and psychiatric disorder (a case report)]. AB - A 40-year-old poor nutritional Japanese male was admitted to our hospital on June 5, 1989, with a 31-day history of fever. He had been working as a crew member of a ship in South East Asia. Salmonella typhi was isolated from his blood culture. In the course of the disease, intestinal hemorrhage, drug-induced fever and liver dysfunction, DIC, ARDS, and psychiatric disorder were identified. Intestinal hemorrhage occurred after the coagulation test became normal, so it was thought that the intestinal hemorrhage did not correlate with DIC. The patient was treated with CP, ABPC and supportive therapy. He became well, and ARDS and psychiatric disorder were disappeared. He was discharged on the 118th day of illness. Drug-induced fever was thought as one of the allergic reaction and the causative drug was not identified by LST. It was suspected that psychiatric disorder correlated with poor nutrition. Supportive therapy such as mandatory bed rest, intravenous hyperalimentation and low-volume blood transfusions, as well as an antimicrobial treatment were important for the inhibition of shock and/or intestinal perforation. PMID- 2258654 TI - [Transacylation systems in mammalian cells]. PMID- 2258655 TI - [Secretory GM3 sialidase during the cell growth]. PMID- 2258656 TI - [Phospholipids and their metabolism in nuclei--the possible roles in nuclear functions]. PMID- 2258657 TI - [Molecular genetics of urea cycle diseases]. PMID- 2258659 TI - [Parathyroid gland]. PMID- 2258658 TI - [Pathogenesis and treatment of hypertension]. PMID- 2258660 TI - [Anti-DNA antibody, anti-idiotypic antibody and systemic lupus erythematosus]. PMID- 2258661 TI - [Diagnosis of digestive tract cancer using cDNA probe and monoclonal antibody]. PMID- 2258662 TI - [Cancer diagnosis by oncogenes]. PMID- 2258663 TI - [Genetic diagnosis for leukemias by oncogenes]. PMID- 2258664 TI - [Clinical diagnosis of the pathogenesis of coronary spastic angina; division of cardiology]. PMID- 2258665 TI - [Pathophysiological findings, treatment and prognosis of angina pectoris]. PMID- 2258666 TI - [Early and long-term results of percutaneous transluminal coronary angioplasty in angina pectoris]. PMID- 2258667 TI - [Characteristics and clinical significance of silent myocardial ischemia during ambulatory electrocardiographic monitoring in patients with ischemic heart disease]. PMID- 2258668 TI - [Prognosis of silent myocardial ischemia and its strategy for treatment]. PMID- 2258669 TI - [The involvement of free radical formation in the post-ischemic neuronal damage]. PMID- 2258670 TI - [Insulin treatment of diabetes mellitus]. PMID- 2258671 TI - [Influenza]. PMID- 2258672 TI - [Recent advances in the diagnosis and treatment of pancreatitis]. PMID- 2258673 TI - [Ventricular tachyarrhythmia]. PMID- 2258674 TI - [Clinical features of hypothalamic disorders]. PMID- 2258675 TI - [Electronic endoscope for the gastrointestinal tract (Videoendoscope)]. PMID- 2258676 TI - [Echocardiographic diagnosis of ischemic heart disease]. PMID- 2258677 TI - [Autoimmune thyroid disease]. PMID- 2258678 TI - [Regulation of thrombopoiesis]. PMID- 2258679 TI - [ACE kininase inhibitor]. PMID- 2258680 TI - [Fabrication and mechanical properties of sintered hydroxyapatite]. PMID- 2258681 TI - [Respiratory neurons in medullary reticular formation which directly project to hypoglossal motoneurons in cats]. AB - The present study was carried out to determine the location of the excitatory premotor neurons projecting to the hypoglossal motoneurons (XII MNs) that show respiratory activities in pentobarbital-anesthetized cats. Projections from these hypoglossal premotor neurons to the phrenic motoneurons were also investigated. The following results were obtained. (1) Injection of a fluorescent dye (Fast Blue, FB) into the hypoglossal nucleus and another fluorescent dye (Nuclear Yellow, NY) into the phrenic nucleus the cells in the medullary reticular formation labelled retrogradely with FB and/or NY mainly in the region ventrolateral to the nucleus of the tractus soritarius (vl-NTS) and dorsomedial to the nucleus ambiguus (dm-AMB). (2) There were respiratory neurons in the region vl-NTS and dm-AMB which antidromically responded to the stimulation of the hypoglossal nucleus. Some of them antidromically responded also to the stimulation of the phrenic nucleus. (3) Averaging of the hypoglossal and phrenic nerve discharges by spontaneous spikes of single respiratory neurons in the region vl-NTS and dm-AMB revealed a facilitation in the hypoglossal nerve discharge. In some of these excitatory hypoglossal premotor neurons, a facilitation was also revealed in the phrenic nerve discharge. It was concluded that there were respiratory neurons in the region vl-NTS and dm-AMB which were excitatory premotor neurons projecting to the XII MNs showing respiratory activities. Some of them had excitatory projections to both the hypoglossal and phrenic motoneurons via the bifurcating axons. PMID- 2258682 TI - [Reflex responses of sternocleidomastoid muscle induced by mechanical stimulation of upper anterior tooth and forehead]. AB - Electromyographic coactivation of the sternocleidomastoid muscle (SCM) during masticatory function was observed. To analyze the mechanism of the coactivation, we studied the reflex responses of the SCM induced by mechanical stimulations and tooth-tapping movements. Six healthy subjects with an average age of 26 years were asked to make various kind of efforts using SCM and masseter muscles, then the mechanical taps were applied to a forehead and an upper anterior tooth, and the surface EMG from the SCM and masseter were recorded. The head position during the recordings was controlled in the upright or the rotation position. The gingiva of the tapped teeth was anesthetized in two subjects. EMG signals were rectified and digitized and then analyzed using the signal average program on a computer (NEC SANEI 7T17). RESULTS: 1. Reflex responses of the SCM with a latency of ca. 30 ms were induced by mechanical taps to the forehead and to the anterior tooth. It can result from a stretch reflex. 2. During the tooth-tapping movement at 1 Hz, the SCM activated at ca. 90 ms after teeth contacts. It is Possible that the activity was derived from a central control mechanism or from another reflex other than the stretch reflex. PMID- 2258683 TI - [Movements of facial surface in edentulous patients]. AB - The purpose of this study was to investigate the influence of complete denture on the movement of the soft tissues surrounding the oral cavity during oral function. Total of 71 clinically healthy edentulous patients were selected for this study. Forty-seven points on the skin surface of the face of each subject were selected as measuring points and were marked. The movement of these measuring points under the condition of thrusting of the lips, pulling the mouth corners backward, intentional occlusion and smile were measured three dimensionally when the denture was worn and not worn. The findings were as follows: 1. The changes in the facial structure with and without the denture were marked in the lips. 2. The changes in the movement of the measuring points on the lip surface with and without the denture were found to be large during the thrusting of the lips and pulling the mouth corners backward. 3. The changes in the movement of the measuring points in the lower parts of the facial surface with and without the denture could be measured over a wide range during intentional occlusion. 4. Activities of the mouth corner points were marked, but the changes in the movement with and without the denture were insignificant. PMID- 2258684 TI - [A comparative study of five indices in malocclusion for evaluating treatment needs]. AB - The purpose of this study was to investigate the utility of five indices of malocclusion (NMT, MI, HLDI, OFI and DI) for evaluating the necessity of orthodontic treatment. One dentist scored malocclusion in 40 females (Age: 18 23). Then, another orthodontist assessed the treatment needs for malocclusion on the same subjects. We compared each score with the assessment by the orthodontist and determined the screening level score of the treatment needs for malocclusion. The sensitivity and specificity were calculated for 5 indices respectively. The selection using MI (screening level score: 12) resembled mostly the assessment by the orthodontist, followed by NMT (screening level score: 8) and DI (screening level score: 8). But the time required to score using MI was longer than using DI, and the reproducibility of NMT was inferior to DI. The subjects in this study had a high frequency of crowding (22.5%), and DI was highly correlated to the arch length discrepancy (r = -0.898). From these results, it was suggested that DI was a suitable index for evaluating the treatment needs for malocclusion, particularly crowding. PMID- 2258685 TI - [Clinical, bacteriological, and immunological examination and treatment of two Papillon-Lefevre syndrome patients]. AB - Papillon-Lefevre Syndrome (PLS) is a rare disease accompanied by palmo-plantar hyperkeratosis and rapidly progressive periodontal breakdown of deciduous and permanent dentition. Two unrelated female PLS patients, four and seven years old, with severe periodontal destruction were examined. Antibody titers against seven strains by the enzyme-linked immunosorbent assay (ELISA), microbial cultures from deep periodontal pockets and mouth rinse samples and immunoblotting analysis were performed. Titers against Actinobacillus actinomycetemcomitans (A.a.) were found to be high by the ELISA test. Microbial cultures of A. a. were found in high percentage and immunoblotting results against sonicated extracts of an A. a. Y4 strain had similar patterns. All deciduous teeth were extracted from the younger patient, later permanent dentition erupted uneventfully and A. a. colonies could not be detected. However, the older patient did not exhibit improvement with conventional periodontal therapy and antibiotic (minocycline/erythromycin) treatment and A. a. colonies could be consistently cultured. After a subsequent ofloxacin medication, A. a. colony detection was suppressed. Furthermore, a reduction of gingival inflammation and pocket depth were observed. Therefore, A. a. was associated as an important pathogen in the etiology of periodontal disease in these PLS patients. PMID- 2258686 TI - [Prediction system of facial change]. AB - Three-dimensional simulation of facial change in a patient with severe facial deformity is very effective in not only determining a treatment plan but also in obtaining informed consent. The purpose of this presentation was to introduce the outline of our prediction system of facial change and its preliminary clinical application. (Outline of this system) This system is composed of the following three parts: Input: Three-dimensional digitized data from modified Moire Topography and coloring data of the face taken by the three-dimensional photographing appliance. ANALYSIS: Reconstruction of colored simulation model and transformation by host computer with 32 bit CPU. Output: Display of full-colored simulation model by three-dimensional graphics (Results of clinical application) 1. Three-dimensional reconstructed graphics were well accepted for clinical use, especially for the prediction in orthognathic surgery. 2. Compared with other systems, the following advantages were found: a) Simplified digitizing system using the CCD camera b) Total access time, from initial data input to display of computed picture, was about 20 minutes c) Accurate reproducibility of facial form and color vision. PMID- 2258687 TI - Induction from a single instance: formation of a novel category. AB - This study examines whether preschoolers can use information from a known category to induce a characteristic attribute of a novel, contrasting category based on a single instance. We showed 32 four-year-olds three instances of a Given Category and one instance of a Target Category. These objects could vary along two attribute dimensions, such as color and shape. All instances of the Given Category shared identical values of one attribute (e.g., all were blue), but could have different values of the other attribute (e.g., a circle, a square, and a triangle). The single instance of the Target Category was different from the Given on both attribute dimensions (e.g., a red diamond). Children gave yes/no judgements as to whether additional objects were instances of the Target Category. There were two possible sources of information about the relevance of an attribute to classification: explicit (labeling) and implicit (variation in the Given Category). There were four conditions such that each source of information was either available or not. Both types of information were effective in eliciting inductions of the relevant kind of attribute and the characteristic value of this attribute in the novel category (explicit: p = .0004; implicit: p = .031). This suggests that children use an inductive bias that the instances of two related but distinct categories tend to be alike in the same way. PMID- 2258688 TI - Development of looking with head and eyes. AB - Research into stabilization of gaze has concentrated on how the eyes counterrotate to compensate for head rotation. There is little information on how head movements function as an integral part of gaze stabilization. The head and eye coordination of six adults and six infants was tested under two conditions: tracking a moving target when the body was stationary; fixating a stationary target when the body was turning. Under each condition, both infants and adults turned their heads more than their eyes in stabilizing gaze. The infants were tested at 3-week intervals between the ages of 11 and 28 weeks. During this period, the precision with which head turning was coupled to their own or the target movement developed to near adult level, showing rapid growth between 11 and 16 weeks. However, the infants' ability to couple the eyes onto the target did not change over the tested period, remaining much less precise than the adults'. These findings have important implications for the assessment of abnormal gaze stabilization, which could facilitate the early diagnosis of perceptuomotor dysfunction. PMID- 2258689 TI - Children's understanding of private keys in referential communication. AB - A private key is a referential utterance used to inform selectively. The ambiguity of the utterance conceals meaning from nonselected audience members. The purpose of this study was to examine three aspects of children's understanding of the use of private keys. Experiment 1 concerned children's sensitivity to information in the context of utterance (i.e., the common ground). Experiment 2 examined appreciation of audience design and the speaker's intent. Experiments 3, 4, and 5 explored some reasons for children's problems in understanding private keys. The results show that even first graders are sensitive to common ground information and the speaker's intent. However, audience design is troublesome even for second graders in some situations, probably because they fail to assess the knowledge of the audience members. Private keys are important theoretically because they represent an aspect of referential communication involving the uses of ambiguous utterances that have been ignored by developmental researchers. PMID- 2258690 TI - Intentional and unintentional memory in young children: remembering vs. playing. AB - In an exploration of Istomina's (1975) paradigm contrasting children's recall from an involuntary or game-like context with recall from an intentional or lesson-like context, this study investigated the relative efficacy of asking 4- and 5-year-olds "to remember" or "to play with" a set of 16 pictures or toys in a naturalistic or laboratory setting. The children's behavior and language were measured during two 2-min study phases, after which recall was assessed. Toys promoted different study phase activities and better retention than pictures, asking a child "to remember" a set of toys led to less recall than asking the child "to play" with the toys, and, across all conditions, instructions "to play" and "to remember" elicited differentiated study phase responses but similar levels of retention. PMID- 2258691 TI - Deafness and immediate memory for pictures: dissociations between "inner speech" and the "inner ear"? AB - Born-deaf, orally trained youngsters were examined on two tasks of immediate memory for pictures of objects. The aim was to investigate the extent of speech coding for pictures in immediate memory in a developmental context. The deaf, unlike young hearing children, did not use picture-name rhyme spontaneously as a cue to recall in a paired association task. Nevertheless, they were just as sensitive as reading age-matched hearing controls to spoken word length in recalling pictures by name. This might mean that the deaf use articulatory rehearsal in some immediate memory tasks, but this leads to a paradoxical conclusion. What could "inner speech" in the deaf be for, if it fails to affect their "inner ear" by inducing rhyme sensitivity in the paired associate task? This paradox is discussed in relation to distinctions between covert and overt use of memory cues in the paired recall task and to possible sources of the word length effect in young hearing (8-9 years old) and deaf subjects. PMID- 2258692 TI - Scripts or scraps: reconsidering the development of sequential understanding. AB - A growing literature attests to temporally ordered recall of events by children under 2 years of age. Other data suggest a developmental sequence wherein the ability to reproduce unfamiliar and/or arbitrarily ordered events, and familiar events in other than canonical order develops well after the first ordered productions of events. Early ordering is thus argued to be dependent upon familiarity, rather than upon general temporal principles. This suggestion was investigated by using elicited imitation to assess 21-month-olds' recall of familiar-canonical, familiar-reversed, novel-causal, and novel-arbitrary event sequences. Subjects reproduced canonical and both types of novel sequences in modeled order. On reversed sequences they vacillated between reproducing the events as modeled and "correcting" them to canonical order. The results suggest that temporal organization is not imposed upon an existing unordered event representation, but rather, is an integral aspect of the representation from its initial construction. It is suggested that young children's difficulty with reversed sequences may be attributed to a reluctance to reorganize existing representations, rather than to the absence of applicable temporal principles. PMID- 2258693 TI - Temporal learning in 4 1/2- and 6-year-old children: role of instructions and prior knowledge. AB - The present study investigates effects of different types of instructions (high rate, interval, and minimal) during training with a fixed-interval schedule as a function of prior acquired temporal knowledge. A pretest was used to assess 4 1/2 and 6-year-old children's ability to understand the temporal parameters of a fixed-interval schedule of reinforcement. The results as a whole show that the control exerted by instructions given by the experimenter or elaborated by the subjects themselves on fixed-interval performance of young children depends on the interaction of two factors: development of verbal self-control skills and mastery of knowledge required by the rules forming the instructions. PMID- 2258694 TI - Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. AB - Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall. PMID- 2258695 TI - T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity. AB - This study has examined the cellular and humoral responses underlying the rejection of rat renal allografts bearing an isolated RT1Aa class I MHC disparity. RT1Aa disparate kidneys were rejected promptly by high responder RT1u but not by low responder RT1c recipients (median survival time 10 d and greater than 100 d, respectively). The magnitude and phenotype of the cellular infiltrate were similar in rejecting and nonrejecting RT1Aa disparate kidneys. Paradoxically, graft infiltrating cells and spleen cells from RT1u recipients showed minimal ability to lyse donor strain lymphoblasts in vitro, whereas effector cells from RT1c recipients showed modest levels of cytotoxicity. Injection of RT1u rats with MRC OX8 mAb was highly effective at selectively depleting CD8+ cells from graft recipients but had no effect in prolonging the survival of RT1Aa disparate grafts despite the complete absence of CD8+ cells from the graft infiltrate, which included numerous CD4+ T cells and macrophages. RT1u, but not RT1c, recipients mounted a strong alloantibody response against RT1Aa disparate kidneys. Immune serum obtained from RT1u recipients that had rejected a RT1Aa disparate graft was able, when injected into cyclosporin-treated RT1u recipients, to restore their ability to reject a RT1Aa, but not a third party RT1c, kidney. These results suggest that CD8+ cells in general and CD8+ cytotoxic effector cells in particular are unnecessary for the rapid rejection of RT1Aa class I disparate kidney grafts by high responder RT1u recipients. By implication, CD4+ T cells alone are sufficient to cause prompt rejection of such grafts and they may do so by providing T cell help for the generation of alloantibody. PMID- 2258696 TI - Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. AB - Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation. PMID- 2258697 TI - Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. AB - IgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falciparum-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytic development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibody-dependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations. PMID- 2258698 TI - Expression cloning of a human Fc receptor for IgA. AB - IgA, the predominant isotype in secretions, mediates the neutralization and removal of environmental antigens from mucosal sites. Although cell surface receptors for the Fc region of IgA (Fc alpha R) have been implicated in a variety of immune effector mechanisms, the molecular features of Fc alpha R remain only marginally characterized. In this report, we describe the isolation of a clone from a myeloid cell line cDNA library that directs the expression of a cell surface molecule with IgA binding specificity. The cDNA encodes a peptide of Mr 30,000 including a putative transmembrane region with features atypical of conventional membrane-anchored proteins. Databank searches indicate that the human myeloid cell Fc alpha R sequence is unique, is a member of the immunoglobulin gene superfamily, and is related to Fc receptors for IgG (Fc gamma RI, II, and III) and IgE (Fc epsilon RI). PMID- 2258699 TI - Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). AB - We have developed polyclonal and monoclonal antibodies against human membrane cofactor protein (MCP) to use as tools to investigate the functions of MCP on intact nucleated cells. Two human T cell lines, CEM and TALL, are CR1- and DAF-. Pretreatment of these cell lines with M177 and polyclonal anti-MCP, which inhibit cofactor activity almost completely, resulted in effective C3 deposition immediately following addition of these cells to Mg2+/EGTA/human sera. The deposited C3 remained expressed partly on the cell surface and most of them were gradually converted to C3bi. Some of the deposited C3 were complexed with membrane proteins, since 140- and 250-kD bands became significantly accumulated on SDS-PAGE by treatment with the antibodies. We next tested whether these C3 coated cells were damaged by complement-mediated cytolysis. p18, an inhibitor of membrane attack complex (MAC) formation, was negative in TALL but positive in CEM. TALL was lysed efficiently only by treatment with the polyclonal anti-MCP, while CEM showed only slight lysis with the same treatment. Monoclonal antibodies to MCP, including M177, caused only minimal cell destruction. Based on these results, together with the fact that decay-accelerating factor (DAF) serves as a factor for preventing C3 attack on human cells, we conclude that MCP and DAF cooperatively protect host cells from C3 targeting and, in these T cell lines, MCP is sufficient for preventing C3 deposition even without DAF. After all, human cells undergo almost no autologous complement-mediated cytolysis if they express at least one of the functionally active inhibitors, MCP, DAF, or p18. PMID- 2258700 TI - OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset. AB - Congenitally athymic rats injected with CD45RBhigh CD4+ T cells from congenic euthymic donors developed a severe wasting disease with inflammatory infiltrates in liver, lung, stomach, thyroid, and pancreas. In contrast, recipients of CD45RBlow CD4+ T cells remained well and continued to gain weight. Animals given unfractionated CD4+ T cells, i.e., a mixture of approximately two-thirds CD45RBhigh and one-third CD45RBlow, were protected from the wasting disease, and the incidence of organ-specific inflammation was much reduced compared with that found in recipients of CD45RBhigh cells alone. The data suggest that this latter subset of CD4+ T cells has autoaggressive potential that is inhibited in normal animals by cells of the CD45RBlow CD4+ phenotype. The possible consequences of a breakdown in this immunoregulatory mechanism are briefly discussed. PMID- 2258701 TI - Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils. AB - Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin. We previously purified one such entity, termed p29b. Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences. The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments. The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase. Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment. This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3. Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity. Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent. PMID- 2258703 TI - Effects of interferon alpha on autocrine growth factor loops in B lymphoproliferative disorders. AB - The B lymphoproliferative disorders B chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) produce a number of autocrine growth factors, including tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-1, all of which may induce positive feedback growth loops. If such malignancies depend on these autocrine growth loops for survival, their interruption may be therapeutically valuable. Interferon alpha (IFN-alpha) abrogates TNF- or IL-6-induced proliferation of HCL and B-CLL cells in vitro and has therapeutic activity in these diseases. We have investigated the possibility that IFN-alpha may act by interrupting autocrine growth factor loops. If purified B-CLL or HCL cells are cultured in the presence of TNF, there is induction of mRNA for TNF, IL-1 alpha, IL-1 beta, and IL-6. However, culture in the presence of IFN-alpha in addition to TNF reduced the level of mRNA for all these cytokines, compared with cells cultured in TNF alone. While cytokine mRNA levels were diminished, levels of mRNA for the ribonuclease activator 2-5A synthetase were increased. Analysis of the kinetics of cytokine mRNA production showed that levels fall shortly after the rise of 2-5A synthetase mRNA. IFN-alpha may produce these effects by shortening the half-life of cytokine mRNA, since TNF mRNA half-life in B-CLL and HCL cells is substantially reduced when the cells are cultured with IFN-alpha. These data suggest that IFN-alpha may mediate its therapeutic effects in these malignancies by blocking autocrine growth factor loops. PMID- 2258702 TI - Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1 kb from V(D)J gene. AB - To investigate why somatic mutations are spatially restricted to a region around the rearranged V(D)J immunoglobulin gene, we compared the distribution of mutations flanking murine V gene segments that had rearranged next to either proximal or distal J gene segments. 124 nucleotide substitutions, nine deletions, and two insertions were identified in 32,481 bp of DNA flanking the coding regions from 17 heavy and kappa light chain genes. Most of the mutations occurred within a 2-kb region centered around the V(D)J gene, regardless of which J gene segment was used, suggesting that the structural information for mutation is located in sequences around and within the V(D)J gene, and not in sequences downstream of the J gene segments. The majority of mutations were found within 300 bp of DNA flanking the 5' side of the V(D)J gene and 850 bp flanking the 3' side at a frequency of 0.8%, which was similar to the frequency in the coding region. The frequency of flanking mutations decreased as a function of distance from the gene. There was no evidence for hot spots in that every mutation was unique and occurred at a different position. No mutations were found upstream of the promoter region, suggesting that the promoter delimits a 5' boundary, which provides strong evidence that transcription is necessary to generate mutation. The 3' boundary was approximately 1 kb from the V(D)J gene and was not associated with a DNA sequence motif. Occasional mutations were located in the nuclear matrix association and enhancer regions. The pattern of substitutions suggests that there is discrimination between the two DNA strands during mutation, in that the four bases were mutated with different frequencies on each strand. The high frequency of mutations in the 3' flanking region and the uniqueness of each mutation argues against templated gene conversion as a mechanism for generating somatic diversity in murine V(D)J genes. Rather, the data support a model for random point mutations where the mechanism is linked to the transcriptional state of the gene. PMID- 2258704 TI - Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor alpha (TNF-alpha) and a synthetic TNF-alpha 31-68 peptide. AB - Macrophages are a major source of fibrogenic factors that promote healing of injured tissue. The recruitment of fibroblasts to sites of tissue injury is a prerequisite for optimal repair of tissue damage. In the present study, human recombinant tumor necrosis factor alpha (hrTNF-alpha), a major macrophage-derived cytokine, was demonstrated to be a potent fibroblast chemoattractant, inducing migration at picomolar concentrations. Anti-hrTNF-alpha monoclonal antibody neutralized most of the fibroblast chemotactic activity generated during short term culture of human peripheral blood monocytes stimulated with bacterial lipopolysaccharide, suggesting that TNF-alpha is a major monocyte-derived fibroblast chemoattractant. The portion of the human TNF-alpha molecule responsible for its chemotactic stimulation of fibroblasts appears to reside in residues 31-68. This region is highly conserved between TNF-alpha and lymphotoxin. This peptide is not only itself chemotactic but is also able to block the chemotactic response of fibroblasts to hrTNF-alpha and vice versa, suggesting that they each mediate fibroblast migration through similar mechanisms. These data further underscore the potential importance of TNF-alpha in modulating a variety of fibroblast functions, including chemotaxis and synthesis of collagen, glycosaminoglycans, interleukin 1 alpha (IL-1 alpha) and beta, human histocompatibility leukocyte antigen A and B antigens, collagenase, prostaglandin E2, and IL-6. PMID- 2258705 TI - Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein like molecules. AB - Group A streptococci can be categorized into two classes (I and II) based on immunodeterminants contained within a surface-exposed, conserved region (C repeat domain) of the major virulence factor, M protein. Previous studies have shown that several biological properties correlate strongly with streptococcal class, and thus, there is a strong impetus to precisely define the antigenic epitopes unique to class I and II M proteins. Using synthetic peptides, the binding sites of two class I-specific mAbs were mapped to distinct epitopes within the C repeat region of type 6 M protein (class I). A class II M protein-like gene (type 2) was cloned and sequenced, and the predicted amino acid sequence was compared for homology to class I and II molecules, whose sequences were previously reported. For a given C repeat block 35 amino acid residues in length, 20 residue positions were conserved among all sequences analyzed. Of the 15 variable amino acid positions, only four were class specific, and three of the four positions were localized in the area to which the class I-specific mAbs bound. The predicted secondary structures of class I and II C repeat blocks reveals that they are alpha-helical, except for a single area of disruption. In the class I molecules, the area of disruption corresponds to the class I-specific mAb binding sites. Importantly, the predicted conformational characteristics of this disruption differs for class I and II molecules. The data suggest that only limited changes in amino acid residues differentiate between class I and II molecules in the C repeat region. Therefore, selective (biological) pressures may have contributed to the evolution of these two classes of molecules. PMID- 2258706 TI - Immunoregulatory role of transforming growth factor beta (TGF-beta) in development of killer cells: comparison of active and latent TGF-beta 1. AB - Using recombinant DNA technology, we have generated Chinese hamster ovary (CHO) cell lines that synthesize latent transforming growth factor beta 1 (TGF-beta 1) to study immune regulation by TGF-beta 1. In vitro, latent TGF-beta 1 synthesized by transfectants or added exogenously as a purified complex after activation inhibited CTL generation to a similar extent as seen with acid-activated recombinant human (rHu) TGF-beta 1. In vivo, serum from nu/nu mice bearing CHO/TGF-beta 1 tumors contained significant levels of latent TGF-beta 1 in addition to depressed natural killer (NK) activity in spleens which paralleled that seen in C3H/HeJ mice treated with acid-activated rHuTGF-beta 1. rHuTGF-beta 1 treatment of mice receiving heart allografts resulted in significant enhancement of organ graft survival. Because of possible regulated tissue specific activation, administration of latent rather than active TGF-beta may provide a better route to deliver this powerful immunosuppressive agent in vivo. PMID- 2258707 TI - Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells. AB - The macrophage mannose receptor is an integral membrane protein expressed on the surface of tissue macrophages. After ligation of mannose-rich glycoconjugates or pathogens, the receptor mediates endocytosis and phagocytosis of the bound ligands by macrophages. The cDNA-derived primary structure of the mannose receptor predicts a cysteine-rich NH2-terminal domain, followed by a fibronectin type II region. The remainder of the ectodomain is comprised of eight carbohydrate recognition-like domains, followed by a transmembrane region, and a cytoplasmic tail. Transfection of the mannose receptor cDNA into Cos-I cells is necessary for receptor-mediated endocytosis of mannose-rich glycoconjugate as well as phagocytosis of yeasts. Deletion of the cytoplasmic tail results in a mutant receptor that is able to bind but not ingest the ligated pathogens, suggesting that the signal for phagocytosis is contained in the cytoplasmic tail. PMID- 2258708 TI - The TL region gene 37 encodes a Qa-1 antigen. AB - Of all the biochemically defined mouse MHC class I molecules, the Qa-1 antigens are the only ones for which a gene has not been identified. Recent evidence has suggested that Qa-1 antigens are functional class I molecules and can function as restriction elements for gamma/delta T cells. We have examined the relationship between Qa-1 and the product of gene 37, a presumed novel class I antigen encoded within the TL region. Immunoprecipitation and polyacrylamide gel electrophoresis analysis of the molecules reactive with anti-Qa-1 and anti-37 sera show that the Qa-1 molecule of Qa-1b (Qa-1.2) mouse strains is identical to the product of gene 37 on the basis of molecular weight, pI, and strain distribution. Immunodepletion, biosynthetic labeling, and tunicamycin treatment confirm that the protein encoded by gene 37 in Qa-1b mice is Qa-1.2. In contrast, the anti-37 serum was unable to recognize the Qa-1 molecule in Qa-1a strains. Given the fact that the only allele to gene 37 thus far identified in a Qa-1a strain (A/J) has a termination codon in the alpha 3 domain, our data lead us to conclude that the Qa 1 molecule expressed in Qa-1a mice is not a true allelic product of the gene 37 encoded antigen of Qa-1b mouse strains. PMID- 2258711 TI - Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells. AB - This report describes a salvage pathway whereby activated T lymphocytes revert to nonproliferating cells in the absence of antigen or mitogenic signals. After the removal of mitogenic cytokines, cultured T lymphocytes cease dividing and rapidly begin to undergo cell death. However, the addition of fibroblasts to interleukin 2 (IL-2)-propagated T cells results in prolonged survival of the previously activated T lymphocytes in the absence of proliferation. The prevention of cell death is also achieved by conditioned medium from the fibroblasts. T lymphocytes cultured with fibroblasts or the conditioned medium retain the ability to be restimulated if mitogenic stimuli are added to the culture. The activity is not accounted for by IL-1-7. The studies suggest a stromal cell-mediated, nonspecific mechanism for survival of primed T lymphocytes in a nonproliferating state. PMID- 2258709 TI - Marked antiinflammatory effects of decentralization of the superior cervical ganglia. AB - Intravenous challenge with parasite antigens in Nippostrongylus brasiliensis sensitized rats resulted in anaphylactic shock and, in some animals, death. Surviving animals showed significant drop in mean arterial blood pressure, cardiac output, and blood flow to the trachea, bronchioles, and mesentery. After anaphylaxis, changes in the cellular and protein composition in bronchoalveolar lavage fluids (BALF) were assessed. 8 h after antigen challenge, there was significant influx of inflammatory cells and an increase in the levels of histamine and serum-derived immunoglobulins (IgG and IgM) in BALF. Chemotactic activity for neutrophils was also present in BALF. Once we established this anaphylaxis-induced model of pulmonary inflammation, we sought to determine whether or not the superior cervical ganglia (SCG) modulate this inflammation. We performed bilateral superior cervical ganglionectomy or decentralization of the SCG. Our results show that decentralization significantly reduced mortality (by 68%) after anaphylaxis. Furthermore, the increases in levels of serum-derived proteins, histamine, and influx of cells (especially neutrophils) observed in BALF after anaphylaxis were attenuated by both decentralization and ganglionectomy. By contrast, hemodynamic parameters in the respiratory tract and the presence of neutrophil chemotactic activity in BALF were not influenced by decentralization. Thus, the severity of pulmonary inflammation initiated by systemic anaphylaxis is depressed by bilateral ganglionectomy or decentralization of SCG. PMID- 2258710 TI - Dissociation of the stimulatory activities of staphylococcal enterotoxins for T cells and monocytes. AB - The staphylococcal enterotoxins (SEs) are homologous proteins related in their capacity for stimulating both T cells and monocytes. To assess the importance of conserved structure and sequence to functional activity, the role of the disulfide loop and adjacent sequence in these toxins was evaluated. Contrary to previous reports, we demonstrate here that the disulfide loop was required for the mitogenic activity of SEA and SEB. While T cell-stimulatory activity was compromised, reduced and alkylated SEs retained major histocompatibility complex class II-binding and monocyte-stimulatory activities, suggesting that their inability to induce T cell proliferation was due to failure to interact with T cell receptor (TCR) rather than with class II molecules. Reduction and alkylation did not affect the far-ultraviolet circular dichroic spectrum of SEA, suggesting that the loss of mitogenic activity was not associated with significant changes in secondary structure. The disulfide linkage imparts considerable stability to these toxins as peptide cleavages within the loop of SEB were not associated with detectable loss of function, although cleavage in the conserved sequence outside the loop of SEA resulted in loss of mitogenic activity. This report thus establishes a functional role for a conserved element in SEs, the disulfide loop, and further indicates that their class II- and TCR-binding activities can be dissociated. PMID- 2258712 TI - Determination of glucose turnover and glucose oxidation rates in man with stable isotope tracers. AB - Determination of the turnover rates of glucose gives a more dynamic view of carbohydrate metabolism. Using 2H- or 13C-labelled glucose, stable isotope methods have been established which are free of risk for volunteers or patients and are in accordance with the legal requirements for radiation protection. The aim of the present study was to determine the main parameters of glucose turnover in vivo by using two stable-isotope-labelled glucose molecules, [6,6-2H]glucose and [U-13C]glucose. Under steady state conditions, the following parameters were analysed: glucose turnover rate, glucose oxidation rate, recycling of glucose, hepatic glucose production rate, and glucose clearance. In healthy volunteers the following data were obtained for the glucose turnover rate: 2.42 +/- 0.11 mg/kg x min, glucose oxidation rate 1.34 +/- 0.08 mg/kg x min, glucose clearance 3.04 +/- 0.17 ml/kg x min, and glucose recycling 24.7% (about 0.6 mg/kg x min). Under conditions of the euglycaemic-hyperinsulinaemic clamp (insulin levels about 80 mU/l) the glucose turnover rate increased to 9-10 mg/kg x min, and the hepatic glucose production rate was totally suppressed. Under these conditions identical glucose turnover rates were measured by rate of appearance Ra and euglycaemic hyperinsulinaemic clamp. These data clearly demonstrate that by using differentially labelled glucose molecules at least five parameters of glucose metabolism may be determined in vivo. High insulin levels (70-80 mU/l) stimulate glucose turnover rate by 300-400%, and the glucose infusion rate agrees well with the rate of appearance (Ra) of glucose, determined with [6,6-2H]glucose. Thus, this glucose tracer provides relevant and presumably accurate data under basal and under hyperinsulinaemic conditions. PMID- 2258713 TI - Platelet count, platelet function, coagulation activity and fibrinolysis in the acute phase of inflammatory bowel disease. AB - Twenty two patients with exacerbation of inflammatory bowel disease (19 with Crohn's disease, 3 with ulcerative colitis) and thrombocytosis were tested for possible activation of the coagulation and platelet system. Fifteen patients had abnormal platelet function i.e. unphysiologically high sensitivity in vitro towards ADP 2 mumol/l aggregation induction. In 81.8% of the patients we found enhanced fibrinogen concentrations. In 22.7% of the patients thrombin antithrombin III values exceeded the upper limit of the reference range, and in 68.2% of the patients the D-Dimer concentration exceeded the upper reference limit as a result of reactive fibrinolysis. The altered platelet count and function, and the increased levels of fibrinogen and thrombin-antithrombin III with reactive fibrinolysis activation indicate the presence of prethrombotic factors in patients with exacerbation of inflammatory bowel disease. The presence of enhanced fibrinolysis in these patients might have consequences for the therapeutic treatment. PMID- 2258714 TI - Determination of human serum phospholipase A2. Comparison of two methods. AB - A photometric assay for serum phospholipase A is compared with a radiometric assay specific for phospholipase A2. The methods show a high correlation. The increased phospholipase A activity in sera of patients with inflammatory and non pancreatic necrotizing diseases is attributable to a neutral-active, calcium sensitive phospholipase A2 but not to pancreatic phospholipase A2. Phospholipase A1 did not seem to contribute significantly to the overall activity of phospholipase A. PMID- 2258715 TI - Modification of potassium channel kinetics by histidine-specific reagents. AB - We have examined the actions of histidine-specific reagents on potassium channels in squid giant axons. External application of 20-500 microM diethylpyrocarbonate (DEP) slowed the opening of potassium channels with little or no effect on closing rates. Sodium channels were not affected by these low external concentrations of DEP. Internal application of up to 2 mM DEP had no effect on potassium channel kinetics. Steady-state potassium channel currents were reduced in an apparently voltage-dependent manner by external treatment with this reagent. The shape of the instantaneous current-voltage relation was not altered. The voltage-dependent probability of channel opening was shifted toward more positive membrane potentials, thus accounting for the apparent voltage-dependent reduction of steady-state current. Histidine-specific photo-oxidation catalyzed by rose bengal produced alterations in potassium channel properties similar to those observed with DEP. The rate of action of DEP was consistent with a single kinetic class of histidine residues. In contrast to the effects on ionic currents, potassium channel gating currents were not modified by treatment with DEP. These results suggest the existence of a histidyl group (or groups) on the external surface of potassium channels important for a weakly voltage-dependent conformational transition. These effects can be reproduced by a simple kinetic model of potassium channels. PMID- 2258716 TI - Translocation mechanism of Na-Ca exchange in single cardiac cells of guinea pig. AB - We have studied in single cardiac ventricular cells of guinea pig the ionic translocation mechanism of the electrogenic Na-Ca exchange, i.e., whether Na and Ca ions countercross the membrane simultaneously or consecutively with "ping pong" kinetics. The dose-response relation between the external Ca concentrations [( Ca]o) and the current density of the outward Na-Ca exchange current were measured at three different intracellular Na concentrations [( Na]i) in the absence of external Na. Nonlinear regression curves of the dose-response relation obtained by computer revealed Michaelis-Menten type hyperbola from which the [Ca]o giving a half-maximal response (apparent KmCao or K'mCao) and the apparent maximum current magnitude (I'max) were estimated at each [Na]i. As [Na]i increased, the K'mCao increased progressively and the value of K'mCao/I'max tended to decrease. These results are consistent with the simultaneous mechanism. The K'mCao/I'max values, however, were small and close to each other, so it was not possible to completely preclude a consecutive mechanism. PMID- 2258717 TI - Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier. AB - Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outward current were found. One component was a La3(+)-sensitive current which inactivated and resembled the transient outward current described in other cell types; single-channel observations confirmed the presence of a transient outward current in these guinea pig ventricular cells (gamma = 9.9 pS, [K]o = 4.5 mM). Analysis of envelopes of tail amplitudes demonstrated that this component was absent in solutions containing 30-100 microM La3+. The remaining time-dependent current, IK, activated with a sigmoidal time course that was well characterized by three time constants. Nonlinear least-squares fits of a four state Markovian chain model (closed - closed - closed - open) to IK activation were therefore compared to other models previously used to characterize IK gating: n2 and n4 Hodgkin-Huxley models and a Markovian chain model with only two closed states. In each case the four-state model was significantly better (P less than 0.05). The failure of the Hodgkin-Huxley models to adequately describe the macroscopic current indicates that identical and independent gating particles should not be assumed for this K channel. The voltage-dependent terms describing the rate constants for the four-state model were then derived using a global fitting approach for IK data obtained over a wide range of potentials (-80 to +70 mV). The fit was significantly improved by including a term representing the membrane dipole forces (P less than 0.01). The resulting rate constants predicted long single-channel openings (greater than 1 s) at voltages greater than 0 mV. In cell-attached patches, single delayed rectifier channels which had a mean chord conductance of 5.4 pS at +60 mV ([K]o = 4.5 mM) were recorded for brief periods. These channels exhibited behavior predicted by the four-state model: long openings and latency distributions with delayed peaks. These results suggest that the cardiac delayed rectifier undergoes at least two major transitions between closed states before opening upon depolarization. PMID- 2258718 TI - Mesencephalic fifth nucleus cell responses to thyroid hormone: one population or two? AB - Hypophysectomized Rana pipiens tadpoles 3-6 months old were placed in dl thyroxine (T4) solutions of 4 to 200 micrograms/l for 1-18 days and fixed 1 day after removal from the hormone solution. Exposure times varied inversely with T4 concentration. Mesencephalic fifth nucleus (M-V) cells were counted on both sides, and cell and nuclear sizes were drawn and measured for each tadpole. Changes in M-V cell characteristics correlated well with T4 exposure times and concentrations, as did changes in external tadpole morphology. All T4 concentrations were effective. Cells and nuclei were distinctly larger in all T4 treated groups. The changes were greatest for cell sizes, less for nuclear dimensions, and still less for nucleo-cytoplasmic ratios. Significant changes were seen for minimum and maximum sizes as well as for the mean values. The greatest mean changes were seen at dosages of 50 micrograms/l for 7-9 days. Mean M-V cell numbers are significantly smaller in hypophysectomized tadpoles than in controls (about 420 vs. 650). Thyroid hormone treatment of the hypophysectomized animals abolishes much of the deficit, though M-V cell deaths at the higher concentrations and longer treatment times reduce the apparent increase in numbers. Are the additional cells obtained through cell division, or do they represent a preexisting subpopulation of prospective M-V cells that require stimulation by thyroid hormone for their full differentiation? PMID- 2258719 TI - Hormonally mediated changes in simple reflex circuits during metamorphosis in Manduca. AB - During insect metamorphosis, the nervous system must be reorganized to allow the production of unique behaviors during each life stage. In the hawkmoth, Manduca sexta, it has been possible to follow this postembryonic phase of neuronal development at the level of identified neurons. Of particular interest in the present context are sensory neurons, motoneurons, and interneurons which persist through metamorphosis, but participate in different types of behavior at different stages of life. Many of these neurons undergo striking changes in their dendritic arborizations and axonal projection patterns, which can be correlated with changes in their synaptic interactions with other neurons. Manipulations of the ecdysteroid and juvenile hormone titers, both in vivo and in vitro, implicate these hormones in the regulation of metamorphic changes within the nervous system. Taking advantage of this endocrine control, it has been possible to create heterochronic mosaic animals that allow the relationship between specific cellular changes and behavioral alterations to be tested directly. PMID- 2258720 TI - Metamorphosis and fish vision. AB - Many species of fish exhibit metamorphosis in which dramatic external transformations occur as a consequence of coordinated changes in gene expression within an organism. Because postembryonic development and change appears to be the rule rather than the exception in teleost fish species, we view metamorphosis as one of many developmental strategies in fish which have continued plasticity as a common theme. Metamorphic changes are manifested in the visual system by modification of photoreceptor peak sensitivity, rod photoreceptor cell addition, and retinal reorganization. These changes correspond to significant changes in the natural habitat of the animal and in its visual capabilities as demonstrated behaviorally. Thyroxine is the main metamorphic hormone as has also been found in amphibia. The sequence of metamorphic events occur in all teleosts, but they are compressed in time in direct developing animals suggesting that such animals might prove useful for understanding the evolution of metamorphosis in fish. It seems likely that rod photoreceptors may have evolved in conjunction with the change from larval to juvenile stage through metamorphosis in indirect developing fishes. During evolution, the contraction and/or loss of the larval stage has resulted in earlier appearance of rod photoreceptors during development although they always arise later than cone photoreceptors. This ontogenetic developmental sequence supports Walls's (1942) proposal that cones are phylogenetically older than rods and suggests that rods may have evolved several times. PMID- 2258721 TI - The gastropod nervous system in metamorphosis. AB - Many gastropods, including the sea hare Aplysia californica, undergo metamorphosis in passing from the larval to the juvenile phases of their life cycle. During metamorphosis, the gastropod nervous system is affected by both progressive and regressive neuronal events. In addition to this metamorphic reorganization, the nervous system appears to be centrally involved in initiating metamorphosis. We propose that gastropods not only possess temporally distinct neuronal adaptations for the specific needs of the larval and juvenile phases, but also another transient neuronal adaptation specialized to subserve the metamorphic episode. PMID- 2258722 TI - Metamorphic-like changes in the nervous system of the nematode Caenorhabditis elegans. AB - During postembryonic development of the nematode Caenorhabditis elegans, one class of embryonic motoneurons, the DD cells, respecifies its pattern of synaptic connections. At the same time, a closely related set of postembryonic motoneurons, the VD cells, complete differentiation and assume a pattern of connections equivalent to the original pattern of the DD cells. These types of changes are reminiscent of changes observed in the nervous systems of animals as they undergo metamorphosis. The DD and VD neurons arise through different lineage mechanisms and in the adult, receive different synaptic inputs and make different outputs. The embryonic DD motoneurons are clonally related to one another; whereas the postembryonic VD motoneurons are produced by a repeated sublineage in which each stem cell generates four or five cell types in addition to the VD cells. In spite of these differences, it has been possible to identify only one gene by mutation that effects one of the two motoneuronal classes. Mutations in the gene unc-55 (unc meaning uncoordinated) cause the VD cells to become essentially identical to the DD cells; thus the unc-55 gene product appears necessary and sufficient to transform homeotically the pattern of synaptic connections of an entire class of motoneuron. PMID- 2258723 TI - Retrofitting larval neuromuscular circuits in the metamorphosing frog. AB - Maturation of vertebrate neuromuscular systems typically occurs in a continuous, orderly progression. After an initial period of developmental adjustment by means of cell death and axonal pruning, relatively stable relationships, with only subtle modifications, are maintained between motoneurons and their appropriate targets throughout life. However, among a restricted group of vertebrates (amphibians and especially the anuran amphibians) the sequential maturation of neuromuscular systems is altered by an abrupt reordering of the basic body plan that encompasses cellular changes in all tissues from skeleton to nervous system. Many anuran amphibians possess neuromuscular circuits that are remarkable by virtue of their complete reorganization during the brief span of metamorphosis. During this period motor systems initially designed for the behavioral patterns of aquatic tadpoles are adjusted to meet the drastically different motor activities of postmetamorphic terrestrial life. This adjustment involves the deletion of neural elements mediating larval specific activities, the accelerated maturation of neural circuits eliciting adult-specific activities and the retrofitting of larval neuromuscular components to serve postmetamorphic behaviors. This review focuses on the cellular events associated with the neuromuscular adaptation in the jaw complex during metamorphosis of the leopard frog, Rana pipiens. As part of the metamorphic reorganization of the jaw apparatus there is a complete turnover of the myofiber complement of the adductor mandibulae musculature. Trigeminal motoneurons initially deployed to the larval myofibers are redirected to new muscle fibers. Simultaneously the cellular geometry and synaptic input to these motoneurons is revamped. These changes suggest that trigeminal neuromuscular circuitry established during embryogenesis is updated during metamorphosis and reused to provide the basis for adult jaw motor activity that is far different than its larval counterpart. PMID- 2258724 TI - Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. AB - A series of studies has examined the response of the spinal cord to lesions made at various stages prior to and after metamorphic climax in the clawed frog Xenopus laevis. Complete transections made between Nieuwkoop and Faber (1956) stages 50 and 62 were followed by gradual recovery of righting and coordinated swimming as animals metamorphosed into juveniles (stage 66). Examination of descending axonal projections using horseradish peroxidase (HRP) showed fibers crossing the lesion site and distributing to the caudal lumbar spinal cord. These fibers could be traced from more rostral spinal segments as well as from brainstem injections of HRP. No evidence for rostrally projecting fibers crossing the lesion was obtained. Juvenile frogs of varying ages failed to demonstrate recovery of coordinated swimming or reconstitution of spinal descending pathways. In an additional series of animals, spinal transections were made within 1 or 2 days of tail resorption to assess whether regenerative capacities extended at all into post-metamorphic stages. No evidence for regeneration was found. Studies of metamorphosing frogs after spinal transections showed that fibers crossed the lesion within 5-12 days of transection, well prior to the end of metamorphic climax; however, in some cases in which metamorphosis seemed arrested, little regeneration was observed. Immunocytochemical studies showed that fibers containing serotonin (5-HT) were included in the population of axons that rapidly crossed the lesion after transection at metamorphic stages. These results are compared to those for lesions of the dorsal columns and other systems in developing and juvenile Xenopus. It is suggested that both metamorphosis-related hormonal changes, and axon substrate pathways, may affect the regenerative response in the Xenopus central nervous system (CNS). PMID- 2258725 TI - The developing visual system and metamorphosis in the lamprey. AB - Metamorphosis of the sea lamprey, Petromyzon marinus, is a true metamorphosis. The larval lamprey is a filter-feeder who dwells in the silt of freshwater streams and the adult is an active predator found in large lakes or the sea. The transformation usually occurs in the fifth or sixth year of life. Enlargement of the eye has been long accepted as a distinctive indication of metamorphosis in the sea lamprey, but it had been thought that this was because eye development in the larva was arrested after the formation of only the small central region. Recent studies indicate that all of the retina begins its development in the larva and that ganglion, amacrine, and horizontal cells differentiate in the peripheral retina of the larva. Retinal development is arrested during the premetamorphic period, to be resumed during metamorphosis. Metamorphic contributions include the differentiation of photoreceptor and bipolar cells. With the early appearance of ganglion cells, retinal pathways to the thalamus and tectum are established in larvae, as is a centripetal pathway. Tectal development spans the larval period but a spurt in tectal growth and differentiation is correlated with the completion of the retinal circuitry late in metamorphosis. The metamorphic changes in retina and tectum complete the functional development of the visual system and provide for the adult lamprey's predatory and reproductive behavior. PMID- 2258727 TI - Neurometamorphosis. PMID- 2258726 TI - Neuronal adaptation accompanying metamorphosis in the flatfish. AB - Flatfish provide a natural paradigm to investigate adaptive changes in the central nervous system of vertebrates. During their metamorphosis, the animals undergo a 90 degrees tilt to one side or the other to become the bottom-adapted adult flatfish. The eye on the down side is pushed over to the up side. Thus, vestibular and oculomotor coordinate systems rotate 90 degrees relative to each other. As a result, during swimming movements different types of compensatory eye movements are produced before and after metamorphosis by the same vestibular stimulation. Intracellular staining of central neurons with horseradish peroxidase revealed that in postmetamorphic flatfish second-order horizontal canal neurons contact vertical eye muscle motoneuron pools on both sides of the brain via pathways that are absent in all other vertebrates studied. These unique connections provide the necessary and sufficient connectivity to adapt the flatfish's eye movement system to the animals' postmetamorphic existence. Although the adult fish has a bilaterally asymmetric appearance, the central nervous connectivity reestablishes symmetry in the vestibulo-oculomotor system. PMID- 2258728 TI - Neurometamorphosis. AB - This article introduces this special issue of the Journal of Neurobiology by reviewing several basic issues in metamorphosis as they specifically relate to the nervous system. It promotes the idea that metamorphic changes in the nervous system (neurometamorphosis) represent adaptive restructurings rather than recapitulations of evolutionary transitions. It introduces, but leaves unresolved, the question of whether neurometamorphosis is achieved primarily as a delayed phase of embryonic neurogenesis or as a special neurogenic period. It points out that respecification of old neurons and the addition of new neurons are the main contributory pathway of neural restructuring at metamorphosis, that respecification can be dramatic and seems to be preferred over the elimination and replacement of particular neurons. It also highlights the question of how much the central rewiring during metamorphosis is driven by trophic interactions with the changing body of the metamorphic animal and to what extent neurometamorphosis is driven by the direct action of metamorphic hormones on the neural elements themselves. Finally, this article introduces the question of the cellular and molecular pathways of neurometamorphosis, from the role of the nervous system in triggering the event to the receptor mediated changes in gene expression. Further details on all of these issues are to be found in the articles that make up the rest of this special issue. PMID- 2258729 TI - The development of the lamprey pattern generator for locomotion. AB - The life cycle of the lamprey includes a larval stage that can last for several years. The motor behavior of the larval lamprey, the ammocoete, has been only minimally studied and little is known of the neural correlates of that behavior. Comparison of known larval behavior to that of adults leaves unclear whether there are large or small changes in the spinal nervous system during transformation. The motor output of isolated larval and transforming spinal cords when stimulated to "swim" with D-glutamate has some differences from that of comparable adult preparations, but shares many important features with adults. Primarily, the fictive swimming is less well regulated and less stable than adults of the same species. We propose that a major difference in the structure and organization of the central pattern generator for locomotion between adults and ammocoetes is a relative lack or immaturity of some cell types that participate in the coordination of the segments and the generation of the rhythm of the periodic bursting. PMID- 2258730 TI - Constant topological organization of the coleopteran metamorphosing nervous system: analysis of persistent elements in the nervous system of Tenebrio molitor. AB - Evidence is provided that the topological organization of the larval neuropil is preserved during metamorphosis of Tenebrio molitor. Constancies in neuronal organization were due in part to persistence of individual neurons whose morphologies were individually followed. It appears that the phenomenologically static situation of the metamorphosing neuropil is achieved by stabilization and regulation due to cellular interactions. Comparisons are made with features of hemimetabolan postembryogenesis. PMID- 2258731 TI - Perspectives on cardiovascular fitness and SCI. AB - The purpose of these papers is to review and discuss the fundamental concepts and problems underlying cardiovascular fitness and spinal cord injury. Particular attention is paid to several modes of exercise available to individuals with spinal cord injury (SCI)--voluntary arm-crank and wheelchair ergometry, electrical stimulation leg cycle ergometry, and combined voluntary arm-cranking and electrical stimulation leg (hybrid) exercise. The effects of level of injury, active muscle mass, and sympathetic dysfunction upon acute central hemodynamic adjustments during exercise testing and chronic training adaptations are discussed for both quadriplegics and paraplegics. Several topics for future research are suggested. PMID- 2258733 TI - Hyponatremia in spinal cord injury. AB - Hypoosmolar hyponatremia (serum Na+ less than 130 mmol/L) has proven a common and incompletely explained phenomenon in the spinal cord injured patient. When present, it has generally been preceded by excessive fluid intake and environmental/dietary factors which reversibly restrict free water excretion. We have attempted to more fully characterize the determinants of SCI-associated hyponatremia by retrospectively analyzing its features and treatment response in a series of 14 hyponatremic SCI patients. In most instances, hyponatremia could be attributed to uncontrolled fluid intake in the presence of an acute or semiacute illness and thus stimuli for non-osmotic releases of arginine vasopressin. Treatment measures generally included administration of 3% saline, with all patients recovering uneventfully from their episode of hyponatremia. PMID- 2258732 TI - Physiologic responses of elite paraplegic road racers to prolonged exercise. AB - The purpose of this study was to determine cardiopulmonary and selected metabolic responses in spinal cord injured (SCI) paraplegics during prolonged arm crank exercise (ACE). Six male and one female elite SCI paraplegic (T4-12 lesions) road racers performed 40 continuous minutes of ACE at 60% of peak ACE oxygen uptake (VO2). Blood samples (30 ml) were collected via antecubital venipuncture at rest and minutes 20 and 40 of ACE for determinations of hemoglobin, hematocrit, serum free fatty acid (FFA), and blood lactate (LA) concentrations. No significant differences were observed over time for VO2 or pulmonary ventilation. Heart rate recorded at minutes 30 and 40 was significantly elevated above HR at minutes 10 and 20 of ACE indicating the presence of an upward drift in HR in paraplegics performing prolonged ACE. Compared to rest, LA concentration was significantly higher at minute 20 and remained relatively stable thereafter. A significant increase in FFA concentration at minute 40 combined with a significant decline in the respiratory exchange ratio suggested a preference for lipid substrate utilization by exercising muscle as ACE continued. The data indicate that the autonomic sympathetic nervous system impairment associated with paraplegia had no apparent adverse effects on cardiopulmonary or metabolic adjustments to prolonged ACE in these well-trained subjects. PMID- 2258734 TI - Gustatory responses of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. AB - 1. In recordings made from 3,120 single neurons, a secondary cortical taste area was found in the caudolateral part of the orbitofrontal cortex of the cynomolgus macaque monkey, Macaca fascicularis. The area is part of the dysgranular field of the orbitofrontal cortex and is situated anterior to the primary cortical taste areas in the frontal opercular and adjoining insular cortices. 2. The responses of 49 single neurons with gustatory responses in the caudolateral orbitofrontal taste cortex were analyzed using the taste stimuli glucose, NaCl, HCl, quinine HCl, water, and blackcurrant juice. 3. A breadth-of-tuning coefficient was calculated for each neuron. This is a metric that can range from 0.0 for a neuron that responds specifically to only one of the four basic taste stimuli to 1.0 for one that responds equally to all four stimuli. The mean coefficient for 49 cells in the caudolateral orbitofrontal cortex was 0.39. This tuning is much sharper than that of neurons in the nucleus of the solitary tract of the monkey, and sharper than that of neurons in the primary frontal opercular and insular taste cortices. 4. A cluster analysis showed that at least seven different groups of neurons were present. For each of the taste stimuli glucose, blackcurrant juice, NaCl, and water, there was one group of neurons that responded much more to that tastant than to the other tastants. The other groups of neurons responded to two or more of these tastants, such as glucose and blackcurrant juice. In this particular region neurons were not found with large responses to HCl or quinine HCl, although such neurons could be present in other parts of the orbitofrontal cortex. 5. On the basis of this and other evidence it is concluded that in the caudolateral orbitofrontal cortex there is a secondary cortical taste area in which the tuning of neurons has become finer than in early areas of taste processing, in which foods, water, and NaCl are strongly represented and where motivation dependence first becomes manifest in the taste system. PMID- 2258735 TI - Modulation of activity of spindle afferents recorded in trigeminal mesencephalic nucleus of rabbit during fictive mastication. AB - 1. These experiments were based on the findings that antidromic firing is observed in first-order sensory afferents during fictive locomotion and were designed to test the hypothesis that a similar central modulation of afferent discharge occurs during mastication. To do this, spindle afferents were recorded in the trigeminal mesencephalic nucleus (Mes V) of anesthetized and paralyzed rabbits during fictive mastication. The cortical masticatory area was stimulated to induce mastication, and activity of the XIIth or the Vth nerves were recorded to monitor the masticatory motor rhythm. 2. Although we could find little evidence that antidromic discharges invade the somatic region of this class of sensory afferents, we did discover a previously unrecognized type of modulation of afferent firing. 3. Of 83 slowly adapting muscle spindle afferents, 33 were modulated during fictive mastication. In 28 cases, the modulation consisted of a phasic inhibition, whereas for the remaining units it could be either a phasic excitation (n = 2) or an excitation alternating with an inhibition (n = 3). 4. Rapidly adapting units were also tested when encountered. Tonic or phasic excitation was never observed. The presence of inhibition could not be verified for this population because tonic activity could not be maintained by passive stretch. 5. The main electroneurogram (ENG) burst of the XIIth and Vth cranial nerves occurred during the opening phase of the masticatory cycle, and in all cases where the records were clear (22 out of 33), phasic inhibition of the afferents coincided with the ENG burst. 6. There was no difference in the distributions of the modulated and of the unmodulated units along the length of the Mes V nucleus. 7. Approximately 40% of trigeminal spindle afferent cell bodies have dendrites, and we suggest that these are the ones rhythmically modulated during fictive mastication. The possible role of this modulation is discussed. PMID- 2258736 TI - Epileptiform activity in the hippocampus produced by tetraethylammonium. AB - 1. The epileptiform discharges in the CA3 region of the rat hippocampal slice produced by bath application of the potassium channel blocker tetraethylammonium (TEA) were investigated. The effects of a convulsant (5 mM) and subconvulsant (0.5 mM) concentration of TEA on the mossy fiber-evoked synaptic currents were studied by the use of voltage-clamp techniques to determine whether TEA, like 4 aminopyridine (4-AP), another potassium channel blocker and convulsant, increased both inhibitory and excitatory components of the synaptic response. 2. At extracellular potassium concentrations of 2.5 mM, TEA (5 mM) was found to produce spontaneously occurring epileptiform discharges that could be recorded extracellularly. The intracellular correlate of the epileptiform discharge, the paroxysmal depolarizing shift (PDS), could be reversed in polarity by depolarizing the membrane and was associated with a large increase in membrane conductance. These results suggest that a synaptically mediated potential underlies the generation of the epileptiform discharge. 3. The reversal potential for the PDS was dependent on the time, relative to the extracellularly recorded field discharge, at which the measurement was made. In current clamp the mean reversal potential of the PDS measured at the midpoint of the extracellular discharge was -3.3 +/- 2.9 (SE) mV (n = 9). The reversal potential of the PDS was considerably more negative when measured either before or after the midpoint of the extracellular discharge, suggesting the presence of an inhibitory synaptic component. In voltage clamp similar results were obtained and a large conductance change was found to be associated with the PDS. These results suggest that the synaptic conductance associated with the PDS has both inhibitory and excitatory components. 4. TEA increased significantly the mossy fiber-evoked, early inhibitory conductance. A convulsant concentration (5 mM) increased the conductance measured 15 ms after the stimulus from 39.7 +/- 8.7 to 87.2 +/- 8.0 nS (n = 6). The reversal potential associated with the conductance depolarized from -68.3 +/- 3.4 to -58.3 +/- 4.0 mV after 5 mM TEA. A subconvulsant concentration of TEA (0.5 mM) also increased the conductance of the mossy fiber evoked response at 15 ms after the stimulus from 49.5 +/- 3.1 to 63.1 +/- 6.1 nS (n = 4) without an associated shift in reversal potential. 5. The late-inhibitory component of the mossy fiber-evoked response, when present, was increased by 5 mM TEA and unchanged by 0.5 mM TEA. 6. The excitatory mossy fiber-evoked synaptic current was studied in the presence of picrotoxin and was found to be increased and prolonged by 5 mM TEA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258737 TI - Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. AB - 1. Supraspinal substrates mediating vagal afferent stimulation (VAS)-induced inhibition of the nociceptive tail-flick reflex were examined by the use of the soma-selective neurotoxin ibotenic acid and the nonselective local anesthetic lidocaine. Fifty rats were studied in the lightly anesthetized state maintained with pentobarbital sodium. 2. The threshold intensity of VAS required to inhibit the tail-flick reflex to a cut-off latency of 10 s was established in all rats. Ibotenic acid (5 or 10 micrograms, 0.5 microliter) or lidocaine (4%, 0.5 microliter) was then microinjected into various regions of the brain stem followed by reestablishment of the intensity of VAS required to produce inhibition of the tail-flick reflex. 3. Microinjections of ibotenic acid into the ipsilateral nucleus tractus solitarius (NTS), medial rostroventral medulla (principally the nucleus raphe magnus; NRM), or bilaterally into the dorsolateral pons (principally the locus coeruleus/subcoeruleus; LC/SC), significantly increased the threshold intensity of VAS required to inhibit the tail-flick reflex. Microinjections of ibotenic acid into either the rostral or caudal ventrolateral medulla (RVLM or CVLM, respectively) ipsilateral to the vagus nerve stimulated or ipsilateral LC/SC did not significantly affect the inhibition produced by VAS. Arterial blood pressure decreases produced by VAS were significantly attenuated or eliminated after microinjections of ibotenic acid into the NTS, RVLM, CVLM, or NRM. Lidocaine microinjected into the ipsilateral CVLM also significantly increased the intensity of VAS required to inhibit the tail-flick reflex. 4. These outcomes obtained with behavioral measures are consistent with the outcomes of the preceding study using electrophysiological measures in establishing that cells in the NTS, LC/SC, and NRM regions and fibers of passage in the CVLM are important in mediating the inhibitory effects of VAS. The present studies confirm previous reports of the importance of the RVLM and CVLM in VAS-produced depressor responses but also demonstrate that the NRM is critical for this cardiovascular response. PMID- 2258738 TI - Cutaneous stimulation evokes long-lasting excitation of spinal interneurons in the turtle. AB - 1. We demonstrated multisecond increases in the excitability of the rostral scratch reflex in the turtle by electrically stimulating the shell at sites within the rostral-scratch receptive field. To examine the cellular mechanisms for these multisecond increases in scratch excitability, we recorded from single cutaneous afferents and sensory interneurons that responded to stimulation of the shell within the rostral-scratch receptive field. A single segment of the midbody spinal cord (D4, the 4th postcervical segment) was isolated in situ by transecting the spinal cord at the segment's anterior and posterior borders. The isolated segment was left attached to its peripheral nerve that innervates part of the rostral-scratch receptive field. A microsuction electrode (4-5 microns ID) was used to record extracellularly from the descending axons of cutaneous afferents and interneurons in the spinal white matter at the posterior end of the D4 segment. 2. The turtle shell is innervated by slowly and rapidly adapting cutaneous afferents. All cutaneous afferents responded to a single electrical stimulus to the shell with a single action potential. Maintained mechanical stimulation applied to the receptive field of some slowly adapting afferents produced several seconds of afterdischarge at stimulus offset. We refer to the cutaneous afferent afterdischarge caused by mechanical stimulation of the shell as "peripheral afterdischarge." 3. Within the D4 spinal segment there were some interneurons that responded to a brief mechanical stimulus within their receptive fields on the shell with short afterdischarge and others that responded with long afterdischarge. Short-afterdischarge interneurons responded to a single electrical pulse to a site in their receptive fields either with a brief train of action potentials or with a single action potential. Long-afterdischarge interneurons responded to a single electrical shell stimulus with up to 30 s of afterdischarge. Long-afterdischarge interneurons also exhibited strong temporal summation in response to a pair of electrical shell stimuli delivered up to several seconds apart. Because all cutaneous afferents responded to an electrical shell stimulus with a single action potential, we conclude that electrically evoked afterdischarge in interneurons was produced by neural mechanisms in the spinal cord; we refer to this type of afterdischarge as "central afterdischarge." 4. These results demonstrate that neural mechanisms for long-lasting excitability changes in response to cutaneous stimulation reside in a single segment of the spinal cord. Cutaneous interneurons with long afterdischarge may serve as cellular loci for multise PMID- 2258739 TI - Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity. AB - 1. An analysis of the spatial and temporal patterns of activity of neurons of the respiratory motor-pattern generation system in an in vitro neonatal rat brain stem-spinal cord preparation is presented. Impulse discharge patterns of spinal and cranial moto-neurons as well as respiratory neurons in the medulla were analyzed. Patterns of motoneuronal discharge were characterized at the population level from recordings of motor-nerve discharge and at the single-cell level from intracellular recordings. These patterns were compared to patterns generated in the neonatal rat and adult mammal in vivo to establish the correspondence between in vitro and in vivo states. 2. The in vitro system generated a complex spatiotemporal pattern of spinal and cranial motoneuron activity during inspiratory (I) and expiratory (E) phases of the respiratory cycle. The respiratory cycle consisted of three distinct phases of neuronal activity (I, early E, and late E phase) similar to the temporal organization of the cycle in the intact mammal. The spike discharge pattern of motoneurons during the I phase consisted of a rapidly peaking-slowly decrementing discharge envelope with a high degree of synchronization on a time scale of 25-50 ms (approximately 20-40 Hz). A similar pattern was generated in the neonate in vivo under conditions comparable with the in vitro state (i.e., nervous system isolated from mechanosensory afferent inputs). However, the I-phase-motoneuron discharge pattern and cycle phase durations differed from those characteristic of the intact neonatal or adult systems in vivo. This difference could be accounted for primarily by removal of vagal mechanosensory afferent inputs. 3. The synaptic drive potentials of spinal motoneurons during the I phase in vitro consisted of a rapidly peaking slowly decrementing potential envelope similar in shape to the spike-frequency histogram of single motoneurons and the envelope of the motoneuron-population discharge. The drive potentials had prominent high-frequency amplitude fluctuations superimposed on the slower drive-potential envelope that were temporally correlated with the generation of motoneuron action potentials. The dominant frequency components of these fast-membrane-potential oscillations (20 35 Hz) were similar to the frequency components of the amplitude fluctuations in the motoneuron-population discharge. One class of medullary neurons with I-phase discharge also exhibited a rapidly peaking-slowly decrementing pattern of impulse discharge and synaptic drive potential with similar high-frequency components.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258740 TI - Inhibition of sensory responses of cat inferior olive neurons produced by stimulation of red nucleus. AB - 1. The sensory responsiveness of cells in the inferior olive is known to be suppressed during certain phases of active movement. These experiments were designed to test the possibility that activity in the rubrospinal pathway contributes to this suppression. We recorded from cells sensitive to light touch located in one of the divisions of the inferior olive, the rostral dorsal accessory olive (rDAO), in cats anesthetized with pentobarbitol sodium. Responsiveness to peripheral stimuli was tested during and after trains of conditioning stimuli delivered to the rubrospinal pathway. 2. All 44 cells in our sample of rDAO neurons showed an inhibition of responsiveness to peripheral stimuli after conditioning stimulation of the rubrospinal pathway. Typical conditioning trains consisted of 0.2-ms pulses at 200 Hz for 100 ms. The mean current required for a reduction in firing probability to 0.5 was 31 microA. Slight increases in intensity often completely inhibited responses to peripheral stimuli. 3. Inhibition of responsiveness showed a delayed time course. Peak inhibition occurred approximately 50 ms after the last pulse in the conditioning train. In many cases there was no demonstrable inhibition during the conditioning train. Increases of train frequency, train duration, or stimulus intensity produced stronger and broader periods of olivary inhibition. 4. The lowest threshold points for eliciting rDAO inhibition coincided with either the magnocellular red nucleus (RNm) or the rubrospinal tract (RST). Stimulation at RST sites produced inhibition of responses in the contralateral but not in the ipsilateral rDAO. Transection of the RST in the upper brain stem blocked the inhibition produced by red-nucleus stimulation without altering the inhibition produced by tract stimulation caudal to the transection. The inhibitory effects thus appear to be caused by activation of the rubrospinal pathway. 5. The inhibitory timing observed in this study may be appropriate for explaining the suppression of olivary responsiveness to contact that has been observed in awake animals. Bursts of movement-related, red nucleus discharge often cease approximately 50 ms before the end of movement. This timing would allow peak inhibition to develop at approximately the time of contact with an object at the end of a goal-directed limb movement. PMID- 2258741 TI - Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression. AB - 1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258742 TI - Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. II. Cortical neurons excited by somatic stimuli. AB - 1. Of the sample of 322 neurons located in somatosensory cortex and tested for their responsiveness to somatic stimulation, 91 (28%) responded to stimuli applied to the skin. The majority were located in the middle cortical layers. Each of the cells subjected to tests with glutamate and acetylcholine (ACh) was rapidly adapting to cutaneous stimuli, giving a response at the onset of skin indentation and sometimes after the stimulus withdrawal. 2. Of the 30 cells tested by pairing basal forebrain (BF) stimulation with cutaneous stimulation. 18 (60%) displayed enhanced responses to the same cutaneous stimulus after the pairing. These effects lasted for greater than 5 min in 17 cases, persisting for as long as the cell was studied, sometimes greater than 1 h. 3. The enhanced responsiveness to cutaneous stimuli could not be reversed by atropine, but in each of the 11 cells where atropine was administered while the BF stimulus was paired with the skin stimulus, the pairing produced no enhancement. 4. We conclude that pairing a BF stimulus with a cutaneous stimulus leads to long-term facilitation of the responsiveness of the cortical neuron subjected to this treatment and that this effect is mediated by the release of acetylcholine from BF cholinergic neurons that act on muscarinic receptors found on neurons in the somatosensory cortex. PMID- 2258743 TI - Basal forebrain projections to somatosensory cortex in the cat. AB - 1. This investigation was designed to identify the source of cholinergic basal forebrain projections to somatosensory cortex in the cat. 2. Injections of horseradish peroxidase (HRP) into cortical areas 3a, 3b, and 1 after a 36 to 48-h survival period, labeled neurons in the basal forebrain. The distribution of retrogradely labeled neurons was compared with the distribution of cells labeled by choline acetyltransferase immunocytochemistry. Most retrogradely labeled neurons in the basal telencephalon were found on the border between the globus pallidus and adjacent structures. Sometimes labeled neurons were also found in both limbs of the diagonal band of Broca. 3. Excitotoxin lesions of these regions of the basal telencephalon led to a profound depletion of acetylcholinesterase containing axons in primary somatosensory cortex. 4. These data lay necessary groundwork for tests of the hypothesis that the cholinergic projection modulates experience-dependent modifications in adult cat somatosensory cortex. PMID- 2258745 TI - Auditory cortical neurons are sensitive to static and continuously changing interaural phase cues. AB - 1. The interaural-phase-difference (IPD) sensitivity of single neurons in the primary auditory (AI) cortex of the anesthetized cat was studied at stimulus frequencies ranging from 120 to 2,500 Hz. Best frequencies of the 43 AI cells sensitive to IPD ranged from 190 to 2,400 Hz. 2. A static IPD was produced when a pair of low-frequency tone bursts, differing from one another only in starting phase, were presented dichotically. The resulting IPD-sensitivity curves, which plot the number of discharges evoked by the binaural signal as a function of IPD, were deeply modulated circular functions. IPD functions were analyzed for their mean vector length (r) and mean interaural phase (phi). Phase sensitivity was relatively independent of best frequency (BF) but highly dependent on stimulus frequency. Regardless of BF or stimulus frequency within the excitatory response area the majority of cells fired maximally when the ipsilateral tone lagged the contralateral signal and fired least when this interaural-phase relationship was reversed. 3. Sensitivity to continuously changing IPD was studied by delivering to the two ears 3-s tones that differed slightly in frequency, resulting in a binaural beat. Approximately 26% of the cells that showed a sensitivity to static changes in IPD also showed a sensitivity to dynamically changing IPD created by this binaural tonal combination. The discharges were highly periodic and tightly synchronized to a particular phase of the binaural beat cycle. High synchrony can be attributed to the fact that cortical neurons typically respond to an excitatory stimulus with but a single spike that is often precisely timed to stimulus onset. A period histogram, binned on the binaural beat frequency (fb), produced an equivalent IPD-sensitivity function for dynamically changing interaural phase. For neurons sensitive to both static and continuously changing interaural phase there was good correspondence between their static (phi s) and dynamic (phi d) mean interaural phases. 4. All cells responding to a dynamically changing stimulus exhibited a linear relationship between mean interaural phase and beat frequency. Most cells responded equally well to binaural beats regardless of the initial direction of phase change. For a fixed duration stimulus, and at relatively low fb, the number of spikes evoked increased with increasing fb, reflecting the increasing number of effective stimulus cycles. At higher fb, AI neurons were unable to follow the rate at which the most effective phase repeated itself during the 3 s of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258744 TI - A region in the dorsolateral striatum of the rat exhibiting single-unit correlations with specific locomotor limb movements. AB - 1. To examine the activity of single units in the lateral striatum of the awake rat with respect to sensorimotor function, 788 units were recorded during locomotion and passive testing. The focus of this report is on 138 units (18%) that fired in relation to sensorimotor activity of a single limb. The remaining units were related to other body parts (16%), to general body movement (38%), or were unresponsive (28%). 2. Firing rates of limb-related units were near zero during resting behavior but increased markedly during treadmill locomotion. Each of the 138 units exhibited a rhythmic pattern of discharge in phase with the locomotor step cycle. Passive testing revealed that 86/97 units tested (89%) responded to passive manipulation of a single limb, exhibiting increased firing rates. Of these, 77 (90%) were related to contralateral and 9 (10%) to ipsilateral limbs. Sixty-one units (71%) were related to a forelimb and 25 (29%) to a hindlimb. Of the 86 units responding to passive manipulation. 34/48 units tested (71%) also responded to cutaneous stimulation of the same limb but no other part of the body. 3. To study in greater detail the rhythmic unit discharges in phase with the locomotor step cycle, computer-synchronized videotape recordings were used to generate perimovement time histograms constructed around discrete locomotor movements of each limb (n = 17 units). Activity of each unit was shown to be restricted to a specific portion of a particular limb's step cycle. The majority of units discharged throughout (8 units) or during a portion of (3 units) the swing phase, whereas other units fired during a portion of stance (3 units), footfall (2 units), or foot off (1 unit). 1. The specificity of unit firing was further demonstrated by the finding that rhythmic discharges, related to discrete locomotor limb movements in the forward direction, were completely absent during spontaneous deviations such as backward or disrupted locomotion. 5. Units related to limb movement were located in the far lateral, especially the dorsolateral, subregion of the striatum. This subregion extend rostrocaudally from A-P +1.6 to -1.0 mm relative to bregma. No clear somatotopic organization was observed, but this issue requires further study. 6. These results show that functional representations of individual limbs can be demonstrated in the lateral striatum of the rat, within a subregion containing terminals of projections from somatic sensorimotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258746 TI - Long-term persistence of enlarged motor units in partially denervated hindlimb muscles of cats. AB - 1. It was the aim of this study to determine the effect that regenerating motor axons would have on enlarged or sprouted motor units that had been established for a relatively long time. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After 200+ days single motor units were isolated, and their isometric contractile properties were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch fatigable (FF), fast-twitch-fatigue-resistant (FR), and slow-twitch-fatigue resistant (S). 3. It had been established previously that regenerating motor axons via L7 returned to the experimental muscles by approximately 100 days. Therefore from 100 to 200 days it was assumed that the sprouted units would be in competition with the regenerating axons. The extent of the original denervations was variable and was estimated from the contralateral side. In soleus most denervations ranged from 83 to 99%; in FDL, from 37 to 81%. 4. In both soleus and FDL there was no evidence that the motor units had sprouted to any less extent than found previously. Within some soleus muscles the largest motor units were developing substantially more force than was expected. However, determination of mean fiber cross-sectional area from muscles frozen, sectioned, and prepared for histochemical analysis showed that this was attributable to increased mean cross sectional area of the type I fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258747 TI - Organization of sensory discrimination and response selection in choice and nonchoice conditions: a study using cerebral evoked potentials in normal humans. AB - 1. It has been suggested that the long-latency "event-related" cerebral evoked potentials (ERPs) reflect certain aspects of the neural processing underlying sensory discrimination in a two-choice reaction time task. The present paper examines the hypothesis that the coupling of these ERPs to sensory discrimination is variable and that the discrimination process is completed at different points during the course of cerebral processing, depending on the actual requirements of the task. 2. We recorded the cerebral evoked potentials and electromyogram (EMG) of the responding muscle in five different reaction time tasks, each requiring sensory discrimination and response selection of varying complexity. In the Choice condition two stimuli were presented, and two separate responses were required. In the two Go-No Go conditions two stimuli were presented, but a response was required to only one or the other of the stimuli. In the two Simple conditions only one stimulus was presented, and one response was required. 3. Under both Choice and Go-No Go conditions, the frequency histogram of the onset latency of the compound muscle action potential for the response to the frequent tone showed a bimodal distribution without overlap, suggesting that there were two distinct types of responder: fast and slow. The comparable histograms for the onset latency of the response to the rare tone also showed a bimodal distribution, but the mean onset latency was prolonged relative to the response to the frequent tone, and the mean separation was less so that the two distributions overlapped each other. 4. Despite the marked difference in response latencies between the fast and slow responders, there was no appreciable difference in cerebral evoked responses between the two groups. Moreover, in response to the frequent tone, all slow responders and, likewise, all fast responders had similar onset latencies of the averaged EMG activity regardless of condition. Nonetheless, fast or slow responders to the frequent tone on one block of trials were also fast or slow responders, respectively, to the rare tone on the same block of trials. 5. These results suggest that two separate sensory discrimination processes are occurring; the first relating to the presence or absence of the frequent (expected) stimulus, and the second relating to the presence or absence of the rare stimulus. The response to each tone can either be generated immediately after that tone is positively identified or, when accuracy is required, can be delayed until both stimuli have been successfully discriminated by the subject. PMID- 2258748 TI - Neural mechanisms underlying the clasp-knife reflex in the cat. I. Characteristics of the reflex. AB - 1. The goal of this study was to characterize the clasp-knife reflex by the use of stretch and isometric contraction of ankle extensor and flexor muscles in decerebrated cats with bilateral dorsal hemisections of their spinal cords at segment T12. 2. Stretch of an extensor muscle evoked inhibition in both homonymous and synergistic extensor muscles. The similarities between homonymous and synergistic inhibition suggest that similar neural mechanisms were responsible. 3. Homonymous and synergistic clasp-knife inhibition showed several characteristic features: 1) inhibition was evoked only by large stretches that produced significant muscle force. Short stretches that did not produce large forces evoked only excitation; 2) the magnitude of clasp-knife inhibition increased with increasing initial motor output, as reflected in the level of rectified EMG; 3) the time course of reflex inhibition evoked by ramp-and-hold stretch was characterized by segmentation of EMG during ramp stretch, dynamic overshoot of inhibition at the end-of-ramp stretch, and slow but usually complete decay of inhibition during maintained stretch; 4) inhibition persisted beyond the termination of stretch, and 5) inhibition showed adaptation to repeated stretch. 4. Isometric contraction of the soleus or medial gastrocnemius, produced by electrical stimulation of the muscle nerve, also evoked powerful synergistic reflex inhibition via similar mechanisms as stretch-evoked, clasp-knife inhibition. Stretch evoked a greater degree of inhibition than did contraction, indicating that receptors responsive to both stretch and contraction contribute to clasp-knife inhibition. 5. The reflex effects produced by stretching the soleus or medial gastrocnemius were not confined to the homonymous and close synergistic muscles. Extensor muscles were inhibited and flexor muscles were excited throughout the hindlimb, which paralleled the pattern of a flexion withdrawal reflex evoked by cutaneous stimulation. 6. Stretch of a flexor muscle, the tibialis anterior, evoked the same spatial pattern and time course of reflex action as stretch of an extensor muscle--inhibition of extensor muscles and excitation of flexor muscles throughout the hindlimb, including homonymous excitation of the tibialis anterior. 7. We conclude that neither Golgi tendon organs nor secondary spindle afferents are likely to contribute significantly to clasp-knife inhibition because their responses to stretch and isometric contraction differ from the reflex actions evoked by stretch and contraction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258749 TI - Neural mechanisms underlying the clasp-knife reflex in the cat. II. Stretch sensitive muscular-free nerve endings. AB - 1. The goal of this study was to determine the contribution of muscular free nerve endings to the clasp-knife reflex by comparing their response properties and reflex actions to the clasp-knife reflex. 2. The responses of single muscle afferents were examined in anesthetized cats using stretch and isometric contraction of ankle extensor muscles identical to those that evoked clasp-knife inhibition in decerebrated and dorsal spinal-hemisectioned cats. 3. Fifty-three stretch-sensitive mechanoreceptor afferents were identified as free nerve ending afferents based on their conduction velocities, location within the muscle, uniformity of response, and dissimilarity to other muscle proprioceptors. The afferent conduction velocities were in both the group III (56%) and group II (44%) range, including five fast-conducting group II afferents (greater than 55 m/s). 4. The stretch response of stretch-sensitive, free nerve endings (SSFNEs) showed several characteristic features: 1) afferents were excited only by large stretches that produced significant passive force; 2) afferent activity began after a brief delay and exhibited segmentation of discharge during ramp stretch, a maximum at the end of ramp stretch, and rapid and complete decay during static stretch, and 3) afferent response adapted to repeated stretches. These properties match those of clasp-knife inhibition described in the companion paper, except that the SSFNE segmentation and maximum were more pronounced and their decay during maintained stretch was more rapid. 5. Isometric contraction produced by electrical stimulation of the muscle nerve, which induced force-evoked inhibition in decerebrated and dorsal hemisectioned cats, also consistently excited SSFNEs. Stretch evoked greater excitation than contraction, indicating that both length and force contribute to SSFNE activity. 6. Stimulation of free nerve endings by squeezing the achilles tendon in cats exhibiting the clasp-knife reflex evoked powerful, homonymous inhibition and a flexion-withdrawal pattern of reflex action -that is, inhibition of extensor and excitation of flexor muscles throughout the hindlimb, which parallels the spatial divergence of the clasp-knife reflex. 7. Intrathecal application of capsaicin, which preferentially blocks the reflex actions of small afferent fibers, blocked clasp-knife inhibition in decerebrated, dorsal hemisectioned cats. 8. The similarities between the reflex actions and response properties of SSFNEs and the properties of the clasp-knife reflex suggest that SSFNEs mediate clasp-knife inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2258750 TI - Measurement of contractile and electrical properties of single human thenar motor units in response to intraneural motor-axon stimulation. AB - 1. A method is described for measuring contractile properties of single human motor units. Conventional human microneurographic techniques were adapted to stimulate individual motor axons in the median nerve, with the use of negative current pulses and a tungsten microelectrode, while recording motor-unit electromyographic activity (EMG) and isometric force responses from the thenar muscles. 2. EMG signals were recorded from both proximal and distal thenar muscle surfaces. Force was recorded in two directions (thumb flexion and abduction). This allowed calculation of the direction and magnitude of resultant force exerted by each unit. 3. Data accepted as originating from a single unit satisfied all the traditional "all-or-none" criteria. Additional criteria also required the following: 1) a wide safety margin between the threshold for unit activation and the current intensity needed to elicit responses from other units; 2) that the characteristic direction in which each unit generated force did not change during the recording period; and 3) whenever F-responses were encountered, the second EMG waveform was identical to the first--a highly improbable event if more than one unit had been excited. 4. Respiration and blood pressure waves introduced baseline fluctuations that distorted the force measurements. These fluctuations were minimized by synchronizing stimuli to the pulse pressure cycle and resetting the baseline electronically just before stimulus onset. 5. Combining motor-axon stimulation at a site remote from the muscle with electronic resetting of the force baseline and delivery of stimuli at fixed intervals after the pulse pressure waves allowed the full time course of human motor-unit twitch and tetanic force and EMG signals to be recorded accurately without signal averaging. PMID- 2258751 TI - Twitch properties of human thenar motor units measured in response to intraneural motor-axon stimulation. AB - 1. The twitch properties of human thenar motor units were examined in response to intraneural motor-axon stimulation. Force components of thumb abduction and flexion were measured before and after tetanic stimulation. The magnitude, direction, and time derivatives of resultant forces, together with axon conduction velocities, were calculated for each unit. 2. Various indexes of contraction and relaxation rate were measured including contraction time (time from force onset to peak), one-half relaxation time (time from peak force to one half that value), normalized maximum contraction and normalized maximum relaxation rates (peak positive and negative time derivatives of the force signal normalized to twitch force), and the times at which these maximum rates occurred. 3. For different units, the directions of resultant forces were approximately evenly distributed between thumb abduction and flexion. At the onset of the experiment, initial twitch forces ranged from 3 to 34 mN, contraction times from 35 to 80 ms, and one-half relaxation times from 25 to 108 ms. 4. Resultant twitch forces were positively correlated to normalized maximum relaxation rates, but not to other rate indexes or to conduction velocity. The various contraction rate measures were correlated to each other, but generally not to relaxation rates. 5. After the first test involving tetanic stimulation, the twitches of most units were potentiated and slowed, especially their relaxation phase. However, the extent of these changes varied considerably between units. In general, units with weak initial forces potentiated most, some up to three-fold. These changes in twitch properties were denoted posttetanic twitch potentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258752 TI - A comparison of human thenar motor-unit properties studied by intraneural motor axon stimulation and spike-triggered averaging. AB - 1. Measurements of twitch contractile properties of human motor units recorded by spike-triggered averaging may be distorted by partial fusion between twitches, because motor units seldom fire at rates below 8-10 Hz. The effects of this fusion were examined by comparing the responses of 27 human thenar motor units when their motor axons were stimulated at 1, 8, and 10 Hz. 2. Resultant forces were calculated from the abduction and flexion force components, together with various contraction and relaxation rate indexes as reported previously. Values for single twitches were compared to measurements made from the unfused force fluctuations ("apparent twitches") of the same units recorded during 8 and 10 Hz stimulation. 3. For all units, stimulation at 8 and 10 Hz caused partial twitch fusion. At 10 Hz, mean values for "apparent twitch" forces, contraction times (CT), and one-half relaxation times (1/2RT) were reduced to 44, 76, and 52% of the corresponding values measured from separate twitches evoked by 1 Hz stimulation. Similar but smaller reductions were seen at 8 Hz. 4. Slow units, with initial twitch CT greater than 60 ms, showed significantly more distortion of all "apparent twitch" parameters when stimulated at both 8 and 10 Hz, compared to fast units (less than 50 ms). 5. The potentiated abduction force component data were compared with abduction forces obtained previously by spike-triggered averaging from the same muscle group. Mean force obtained by spike-triggered averaging ("STA twitch" force: 21 mN) was significantly larger than that measured in abduction in response to either 1 or 10 Hz motor-axon stimulation (14 mN, 6 mN, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258753 TI - Interocular torsional disparity and visual cortical development in the cat. AB - 1. The present experiments were designed to assess the effects of relatively large optically induced interocular torsional disparities on the developing kitten visual cortex. Kittens were reared with restricted visual experience. Three groups viewed a normal visual environment through goggles fitted with small prisms that introduced torsional disparities between the left and right eyes' visual fields, equal but opposite in the two eyes. Kittens in the +32 degrees goggle rearing condition experienced a 16 degrees counterclockwise rotation of the left visual field and a 16 degrees clockwise rotation of the right visual field; in the -32 degrees goggle condition the rotations were clockwise in the left eye and counterclockwise in the right. In the control (0 degree) goggle condition, the prisms did not rotate the visual fields. Three additional groups viewed high-contrast square-wave gratings through Polaroid filters arranged to provide a constant 32 degrees of interocular orientation disparity. 2. Recordings were made from neurons in visual cortex around the border of areas 17 and 18 in all kittens. Development of cortical ocular dominance columns was severely disrupted in all the experimental (rotated) rearing conditions. Most cells were classified in the extreme ocular dominance categories 1, 2, 6, and 7. Development of the system of orientation columns was also affected: among the relatively few cells with oriented receptive fields in both eyes, the distributions of interocular disparities in preferred stimulus orientation were centered near 0 degree but showed significantly larger variances than in the control condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258754 TI - Midwifing a loved one. Some personal reflections. PMID- 2258755 TI - Obstetrics by ear. Maternal and caregiver perceptions of the meaning of maternal sounds during second stage labor. AB - In a study at the University of Colorado School of Nursing, Department of Nurse Midwifery, women's second stage labors were videotaped to study caregiver behavior during second stage labor. Postpartum interviews of the mothers (n = 10) and caregivers (n = 16) were conducted to learn about their responses as they viewed the videotapes. Qualitative analysis was conducted of the transcribed interviews using the Ethnograph computer software. One of the themes emerging from the data was the significance of maternal sounds. Both caregivers and mothers were able to articulate differences between adaptive and nonadaptive sounds according to their quality, pitch, feeling state, and accompanying verbalizations. Data about women's second stage labor sounds have been categorized according to the following maternal states: work/effort, coping, childlike, out-of-control, and with epidural anesthesia. Typical sounds/verbalization, significance, and facilitative caregiver responses are defined for each category. It is concluded that when a "no noise" rule is evoked during second stage labor, valuable behavioral cues are unavailable to guide caregiver behavior. PMID- 2258756 TI - Investigation of institutional differences in primary cesarean birth rates. AB - Differences in primary cesarean birth rates between a maternity center staffed by certified nurse-midwives (CNM) with physician backup on the premises and a university teaching hospital staffed by resident and attending physicians were studied. The study sample included 796 and 804 women, similar in demographics, who received their prenatal and intrapartum care in the respective sites in 1977 and 1978. Study results indicate a significantly lower rate of primary cesarean birth at the maternity center than at the university hospital that was independent of institutional differences in the indications for abdominal delivery. Although cesarean birth was related to contracted pelvis (at labor), fetal malpresentation, and placental bleeding at both institutions, it was significantly associated with preeclampsia, primiparity, fetal distress, and maternal age only at the university hospital. There were no noteworthy differences in pregnancy outcomes for women delivered vaginally or by cesarean, except for more newborns with low Apgar scores among primary cesarean births at the university hospital. A likely explanation for these findings is differing labor and delivery management styles between the providers of care at the two institutions. PMID- 2258757 TI - Role of nutrition in the prevention of preeclampsia. Review of the literature. AB - Preeclampsia has been called a disease of theories. One theory proposes a complex relationship between nutritional imbalance and the pathophysiology of this disease. The theoretical importance of selected nutrients is considered through reference to several recent basic research studies and clinical trials. With the clinical prevention of preeclampsia as a focus, suggestions for outpatient nutritional counseling, dietary alteration, and nutrient supplementation will be offered. PMID- 2258758 TI - Reproductive concerns of women at risk for HIV infection. AB - This qualitative, exploratory study investigated knowledge about perinatal transmission of human immunodeficiency virus (HIV) and perceptions of the childbearing role among women at risk for acquired immunodeficiency syndrome (AIDS) through injection drug use. Content analysis was used to analyze the results of 21 face-to-face, semistructured interviews with women who had a personal history of injection drug use or who were the sexual partners of men who injected drugs. Contextual variables influencing women at risk for HIV infection that were identified included fear of HIV antibody testing, a belief that perinatal HIV transmission is inevitable, support for pregnancy termination in the event of HIV-associated pregnancy, a strong desire for children, pride in mothering behavior, and guilt about the possibility of transmitting HIV to unborn children. AIDS education and counseling for these women will be most effective if these variables are considered. PMID- 2258759 TI - Practicing nurse-midwifery in the medical-legal climate. Intrapartum issues. AB - Clinical management in the intrapartum period is examined from a risk-management perspective. The need for current clinical protocols, obtaining medical consultation when necessary, and clear and complete charting is stressed. PMID- 2258760 TI - Developing competency in the management of the depressed neonate. PMID- 2258761 TI - Pre-treatment review programs. PMID- 2258762 TI - Occupations and the prevalence of major depressive disorder. AB - The prevalence of depression has rarely been studied in a manner permitting comparisons across a range of occupations. This analysis reveals considerable range in prevalence in 104 occupations of major depressive disorder as defined by the Diagnostic and Statistical Manual (ed 3), and measured by the National Institute of Mental Health's Diagnostic Interview Schedule. Five occupations had prevalence rates above 10%. When adjusted for sociodemographic factors, three occupations yield prevalences with statistically significant elevations in the rate, compared with employed persons generally. The three are lawyers, with an odds ratio of 3.6; other teachers and counselors, with an odds ratio of 2.8; and secretaries, with an odds ratio of 1.9. Exploration of possible sources of these differences concludes the paper. PMID- 2258763 TI - Cases of alleged asbestos-related disease: a radiologic re-evaluation. AB - Chest radiographs were re-evaluated from 439 active and retired tireworkers previously designated as having a condition consistent with an asbestiform mineral exposure. The review was performed in an independent manner by three board-certified radiologists according to guidelines from an international classification system. The percentage of cases with abnormalities consistent with an asbestiform mineral exposure found separately by the three radiologists was 3.7, 3.0, and 2.7%. Application of an algorithm to form a consensus evaluation indicated that approximately 3.6% (16) of the subjects evaluated may have a condition consistent with an asbestos exposure. A more detailed review, however, revealed that only 11 workers, or 2.5% of the total, would have a reasonable likelihood of having such a condition. Most cases were normal and the majority of abnormalities present on the radiographs evaluated were nonoccupational in origin. Prevalent conditions identified included healed tuberculosis, histoplasmosis, emphysema, discoid atelectasis, effusions, healed rib fractures, scarring due to infection or old inflammatory disease, possible cancer, miscellaneous nonspecific linear markings consistent with cigarette smoking and aging, and heart and vascular system diseases--the latter evidenced by an abnormally large number of subjects with healed coronary artery bypass surgery and pacemaker implants. In summary, the best estimate from this study indicates that possibly 16 (3.6%), but more realistically 11 (2.5%), of the 439 tireworkers evaluated may have a condition consistent with exposure to an asbestiform mineral. This represents a 40-fold difference between the re-evaluation results and the original survey work. PMID- 2258764 TI - New developments in the Life Table Analysis System of the National Institute for Occupational Safety and Health. AB - In the 1970s, the National Institute for Occupational Safety and Health developed a Life Table Analysis System to analyze occupational cohort studies. We have updated the original system by adding two new features: direct standardization with a test for linear trend, and analyses by lagged exposure (either duration of exposure or cumulative exposure). We have also updated US reference rates through 1989. The updated systems and documentation (version F) are available upon request. In collaboration with the National Cancer Institute, we have also developed multiple cause-of-death rate files, which consider contributory as well as underlying cause. These files (also available upon request) will enable investigators to derive the expected prevalence of diseases at death, which can then be compared with the observed prevalence in an exposed cohort. Work is currently underway to produce a personal computer version of the Life Table Analysis System. PMID- 2258765 TI - Safety performance among union and nonunion workers in the construction industry. AB - This study examined differences between union and non-union construction workers in terms of safety performance and of demographic, employment, and sociopsychological factors related to safety performance. Data were collected by questionnaire in a larger study on construction workers' safety practices among 384 workers employed at nine nonresidential construction sites in the Baltimore metropolitan area. Union and nonunion construction workers differed in terms of safety performance and certain factors related to safety performance. Higher safety performance scores among union workers were, however, related to the fact that union members were older than nonunion members. Moreover, other differences were related to elements over which unions have more control. Findings revealed the need of special attention of the nonunion youngest members, and of additional evaluation of the actual and potential role played by unions in occupational safety. PMID- 2258767 TI - What's in a name. Taking poetic license with occupational and environmental medicine. PMID- 2258766 TI - Incorporating environmental medicine into training programs in occupational medicine. AB - Demand is increasing rapidly for medical evaluation and management of individuals and groups exposed to chemical, physical, and biologic hazards in the non workplace environment. Because general physicians are ill prepared to respond and no existing specialty has obvious expertise, occupational physicians who have some relevant background could have a central role to play in filling these perceived needs. However, incorporation of environmental medicine into the specialty will require reexamination of our skills and training. The focus of this essay is to explore aspects of environmental medicine practice that demand expansion of the current repertoire of skills. Based on these, we propose modifications of training that could facilitate such expansion without sacrifice of the core principles of traditional occupational medicine. PMID- 2258768 TI - An opportunity lost, an opportunity regained: the challenge for an evolving specialty. PMID- 2258769 TI - Environment and the American Board of Preventive Medicine. PMID- 2258770 TI - Monitoring of nitrous oxide in operating rooms: identification of sources and estimation of occupational exposure. AB - In an academic hospital, nitrous oxide (N2O) levels were measured continuously and detailed workplace observations made in three different operating rooms for 18 days. The study was designed to determine the exposure of different categories of staff to nitrous oxide, to localize and quantify the emissions, and to predict and validate the effect of corrective measures. Nitrous oxide levels appeared to be highly time and place dependent; all staff, except for surgeons, were exposed to N2O levels (8-hour time-weighted average) above 25 parts per million. The most important contributor to total release of N2O was the ventilator (about 70%), especially during artificial respiration of the patient. A simulation model was developed and used to predict the effect of technical improvement of the ventilators and use of scavenging during anesthesia (total 58% reduction of release). The model shows that under these conditions, without altering room ventilation rates, room air circulation can be increased up to 50% without exceeding the proposed threshold limit value (25 parts per million). Measurement of N2O levels after intervention showed a reduction in the area surrounding the ventilator of about 80%, thereby reducing occupational exposure of all staff to below 18 parts per million. PMID- 2258771 TI - Using Occupational Safety and Health Administration accident investigations to study patterns in work fatalities. AB - Investigations of fatalities by the Occupational Safety and Health Administration (OSHA) provide the most detailed available information about traumatic workplace deaths that are potentially related to violations of existing safety standards. Comparison of the number of such deaths investigated by OSHA from 1977 to 1986 with the comparable category of deaths reported to the Bureau of Labor Statistics Survey of Occupational Injuries and Illnesses indicates that the overall magnitudes have been roughly similar. The OSHA data contain more information than other sources and are especially valuable for analyses of fatalities at smaller workplaces. The OSHA data show that death rates decline sharply with establishment size; the inverted "U" pattern for lost workday injury rates is absent. Because accident investigations are conducted as part of an administrative system, the OSHA data can be influenced by changes in administrative policies. Changes over time in the percent of fatalities in which violations of OSHA standards were cited have clearly been influenced by changes in OSHA citation policy and thus do not provide a valid measure of the rate of violation-caused deaths. Realization of the epidemiological value of this data source depends upon a commitment from OSHA to maintain consistency in investigating accidents and to improve its data collection methods. PMID- 2258772 TI - What is environmental medicine? PMID- 2258773 TI - Implementation of the Federal Hazard Communication Standard: does training work? AB - A joint labor-management training program intended to bring a large US manufacturing firm into compliance with the training requirements of the Federal Hazard Communication Standard appeared to achieve increases in employee knowledge and improved work practices. The program also evidenced positive indirect effects on management's institution of hazard control measures and organizational handling of health and safety issues. Most observed effects were maintained over a 2-year period after the training. More interactive, trainer-intensive delivery methods to smaller groups were associated with more positive effects on reported training usefulness and changes in work practices and working conditions. PMID- 2258774 TI - Polypropylene and colorectal adenomas: searching for prevalence. PMID- 2258775 TI - Colorectal cancer and polypropylene exposure: how good is the evidence? PMID- 2258776 TI - Stress and hypertension. AB - The relationships between stress and hypertension have been evaluated extensively. Acutely, stress has been shown to increase blood pressure by increasing cardiac output and the heart rate without affecting total peripheral resistance. Acute stress has been found to increase levels of catecholamines, cortisol, vasopressin, endorphins and aldosterone, which may in part explain the increase in blood pressure. However, a primary role for the activation of the sympathetic nervous system has recently been suggested in several studies. Studies in the rat are beginning to determine specific central nervous system pathways which transform stressful stimuli into signals triggering a cardiovascular response without direct cortical participation. Furthermore, acute stress reduces renal sodium excretion, which contributes to an increase in blood pressure. Several studies suggest that prolonged stress may predispose people and animals to prolonged hypertension and certain populations are at risk for the development of stress-induced hypertension. It is likely that prolonged stress induced hypertension is the result of neurohormonal trophic factors which cause vascular hypertrophy or atherosclerosis. Because stress can affect measurement of blood pressure due to the phenomenon of 'white-coat hypertension', ambulatory blood pressure monitoring is emerging as an important feature in the evaluation of patients with hypertension. Finally, relaxation techniques are being used increasingly in the treatment of patients with hypertension. PMID- 2258777 TI - Differences between observers in blood pressure measurement with an automatic oscillometric recorder. AB - Blood pressure measurements made with a Dinamap oscillometric blood pressure recorder by two observers on a total of 2596 male and female subjects aged between 25 and 59 living in nine British towns were examined for evidence of observer differences. After adjusting for age, body mass index and town, significant differences between the two observers were found for systolic pressure, 3.07 mmHg (P = 0.001) for male subjects and 2.08 mmHg (P = 0.036) for female subjects. Observer differences for mean arterial pressure and diastolic pressure were less than 1 mmHg and were not significant. The magnitude of observer differences also varied between towns and, when tested statistically, was significant in male subjects for systolic (P = 0.011), mean arterial (P = 0.009) and diastolic pressure (P = 0.002); for female subjects it was significant only for diastolic pressure (P = 0.023). We conclude that although the highly automated Dinamap has kept observer variation within acceptably low limits in field study conditions, the problem has not been altogether eliminated. PMID- 2258779 TI - Non-pharmacological treatment of hypertension. AB - Weight reduction, alcohol restriction, mild salt restriction, eating a vegetarian diet and increasing aerobic exercise will generally lower the blood pressure in patients with essential hypertension. Eating a diet rich in potassium and reducing caffeine intake may also be helpful in reducing the pressure, but increasing the fiber or calcium intake will generally be ineffective. Reducing fat intake from the usual 40% of total calories to 25-30% may reduce hypertension directly or by weight reduction. Smoking, when combined with excessive caffeine or alcohol intake may have an additive effect on blood pressure. Monotherapy with such behavioral techniques as self-monitoring of blood pressure, biofeedback, meditation, yoga, progressive muscular relaxation or cognitive therapy may reduce the blood pressure to a variable degree, and combinations of these treatments may be even more successful. PMID- 2258778 TI - Self-measured blood pressures at home and during consulting hours: are there any differences? AB - Home blood pressures are lower than casual blood pressures and this difference is probably due to physician-patient interaction in a clinical stress situation. In order to prove this assumption we compared the casual blood pressures of 127 subjects, measured by a physician and by the subjects themselves in the presence of the physician, with self-measured values obtained at home over a 7-day observation period. The casual pressures were higher than the home pressures (delta = 7.6/3.9 mmHg) regardless of whether they were taken by the physician or by the subjects themselves in the presence of the physician. The subjects' casual readings (132.9 +/- 17.5/87.6 +/- 12 mmHg) were slightly, but significantly, higher than those measured by the physician (131.9 +/- 18.4/86.3 +/- 12.6 mmHg) and both systolic and diastolic self-measured casual values were highly significantly correlated with the physician's readings (r = 0.92 and 0.91, respectively; P less than 0.01). PMID- 2258780 TI - Analysis of time trends, individual subject responses and background variation in crossover factorial studies with antihypertensive drugs. AB - In studying patients with mild hypertension, we used a double-blind, randomly allocated crossover, 2 x 2 factorial design to obtain more precise estimates of the effectiveness of individual hypertensive drugs and of the interactions when used in combination. In the present study, we reanalysed data from our own previously completed crossover factorial studies in order to determine the optimal length of phases and to try to exploit patient heterogeneity by comparing blood pressure responses within each patient to the two different drugs in each study. An analysis of the 'weeks within phases' variation (analysis of variance) applied to all phases, to the placebo phases alone and to the active treatment phases alone, of the individual factorial studies and of pooled data from studies of similar design, only revealed differences in the first week of our 4-week phases. Accordingly, we suggest that 4 weeks is an optimal phase length, since only the values from the third and fourth weeks showed the full expression of a drug's antihypertensive effect, avoiding the problem of a carryover effect and the need for a more complex intervening washout placebo phase. Comparing the blood pressure reductions shown by individual patients in response to different antihypertensive drugs using arbitrary criteria of greater than or equal to 5, 10 and 15 mmHg for diastolic and greater than or equal to 5, 10 and 20 mmHg for systolic pressure, we were unable to distinguish between the two separate drugs in each factorial study, due to the magnitude of the background variation which had a coefficient of variation of 5-7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258781 TI - Clinical trials in hypertension: the present and perspectives for the future. AB - Testing antihypertensive drugs solely for their efficacy and safety does not meet modern therapeutic demands. Clinicians need to know how drugs behave during an overdose and how they affect a patient's quality of life. In the future, health economists will be involved much earlier and more intimately in the development of trial methodology, to value a drug's contribution to a patient's lengthened life-span and to compare this effect with the drug's potential contribution to society at large. New trial methodologies will evolve, particularly community trials and case-control (phase IV) studies. Since it is now accepted that control of hypertension alone will not prevent development of coronary artery disease, methodologies and experimental design will focus on 13 major and minor risk factors for coronary artery disease, their interplay with hypertension and their possible control with antihypertensive agents. PMID- 2258782 TI - Trials using a crossover design and ambulatory blood pressure recordings to determine the efficacy of antihypertensive agents in individual patients. AB - The antihypertensive effects of the beta-blocking agent betaxolol and the calcium entry blocker verapamil were compared in a crossover single-blind trial. Seventeen patients with uncomplicated essential hypertension took either betaxolol or a slow-release formulation of verapamil for two consecutive 6-week periods. The sequence of treatment phases was randomly allocated and a 2-week washout period preceded each treatment. The antihypertensive effect of the test drugs was assessed both at the physician's office and during everyday activities using a portable blood pressure recorder. The crossover design of the trial made it possible to evaluate the antihypertensive efficacy of betaxolol and verapamil both in the group as a whole and in the individual patient. The individual patient response to one of these agents was not a reliable indicator of the same patient's response to the alternative agent. Betaxolol brought both office and ambulatory recorded blood pressures under control in a larger fraction of patients than verapamil, although the magnitude of the blood pressure fall in the responders was equal for each drug. These observations stress the need for an individualized approach to the evaluation of antihypertensive therapy. The present results also demonstrate that optimal antihypertensive therapy is still a matter of trial and error. The precise methodology that ought to characterize crossover trials may make it possible to improve the therapeutic approach to hypertensive patients. PMID- 2258783 TI - Use of crossover trials to obtain antihypertensive dose-response curves and to study combination therapy during the development of benazepril. AB - When a new drug is developed, one of the first requirements is to establish the correct dose. Unfortunately, in dose-determination studies, not enough lessons have been learned from the past. Pilot studies are often planned without sufficient statistical power, due to an insufficient number of patients and highly variable blood pressure measurements. In the development of the new angiotensin converting enzyme (ACE) inhibitor benazepril, crossover trials were used to obtain useful information. At the end of phase II of the benazepril development, a double-blind crossover study was carried out with 25 patients, and the results made it possible to redefine the 12- and 24-h effects of benazepril in comparison with placebo. Moreover, the crossover trial allowed an investigation of the biological effects of the treatment. In further work, the efficacy of 10 mg benazepril, administered once a day, was confirmed in comparison with captopril and enalapril, with a beta-risk of less than 20%. Since this crossover study yielded reliable data, and there was no carryover effect, a similar crossover design was used to study the interaction between benazepril and nifedipine. In the past, mistakes were made and many antihypertensive drugs were administered in high doses, with no further beneficial effect on blood pressure and an increased risk of side effects. Work described in this paper shows that fewer but better designed and implemented studies can improve the efficiency and value of dose-finding studies for antihypertensive drugs. PMID- 2258784 TI - Individualizing antihypertensive therapy with enalapril versus atenolol: the Zurich experience. AB - With the present increasing concern for compliance and quality or life during antihypertensive treatment, drug therapy tailored optimally for the individual patient is becoming increasingly important. The aim of the present double-blind crossover study was to analyse the individual as well as the group blood pressure response under enalapril and atenolol. Our results show that the group effects of these drugs did not differ significantly. However, individually, two-thirds of the responding patients showed a preference for either enalapril or atenolol. A response to one drug did not predict a comparable response to the other drug. We conclude that double-blind crossover studies are a possible way of individualizing antihypertensive treatment. However, no appropriate methodology or definitions of terms for these studies have yet been established. PMID- 2258785 TI - Comparative studies in hypertension: some fallacious claims of age-related drug efficacy. AB - Many claims of age-related differential antihypertensive drug effects are invalid because of serious deficiencies in trial design and statistical analysis. Problems include the method of measurement of response, the lack of a suitable control group, the relationship between response and baseline blood pressure, the use of post hoc analyses and the pooling of data from separate trials. Thus far, only the serotonin antagonist ketanserin has been convincingly shown to have a greater antihypertensive effect in old than in young patients. While other drugs may have a similar age-related differential effect, this has not yet been demonstrated in sufficiently sound studies. PMID- 2258786 TI - Intervention trials in elderly hypertensive patients: a review. AB - Results from total and cause-specific mortality from various randomly allocated intervention trials of antihypertensive drug treatment in elderly hypertensives have been reviewed, compared and pooled. Mortality from all causes tended to decrease in all trials, but this decrease was not statistically significant in any of the trials separately, nor when all results were pooled. When the results of all the trials were combined, there was a significant overall decrease in cardiovascular mortality of 28%. This decrease was mainly related to a significant reduction in cerebrovascular mortality of 41%. Mortality from ischaemic heart disease also tended to decrease by 28%, but statistical significance was not reached. PMID- 2258787 TI - Concentration-effect relationships and antihypertensive mechanisms: ketanserin in the treatment of essential hypertension. AB - Concentration-effect relationships were characterized in individual hypertensive patients treated with single and multiple doses of ketanserin. There were significant changes in the concentration-effect parameters during continued treatment, and overall there was a reduction in antihypertensive responsiveness, from -0.47 to -0.25 mmHg/ng per ml. The nature of the changes, however, raises the possibility that there were associated changes in the site and mechanism of the underlying antihypertensive action. It is possible that a peripheral mechanism, perhaps alpha 1-adrenoceptor antagonism, is relatively more pronounced after the first dose whereas a central mechanism, perhaps related to serotonergic antagonism, is relatively more important during chronic treatment. We conclude that this technique of concentration-effect analysis may be useful in exploring mechanisms of action and identifying issues which require further clarification. PMID- 2258788 TI - Prostacyclin in hypertension. AB - Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c)AMP is known to act as a second messenger for platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP, for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side effects, primarily nausea, emesis, flushing, diphoresis and restlessness. In hypertensive patients blood pressure responses are complex and are influenced to some extent by secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and also has an indirect effect by activating the sympathetic nervous system. Thus it is useless as an antihypertensive agent even apart from its debilitating side effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize larger amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension, endogenous synthesis of PGI2 has been evaluated by measuring 2,3 dinor-6-keto-PGF1 alpha and has proved to be defective. Some drugs (cicletanine, thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to abolish their antihypertensive effects. Whether stimulation of PGI2 synthesis affects the antihypertensive efficacy of these drugs is not yet known. PMID- 2258789 TI - Pseudohypertension in hypertensive patients on multiple drug therapy. AB - Differences in blood pressure between direct intra-arterial and indirect cuff measurements have been reported, especially in elderly patients. We investigated the incidence of pseudohypertension among hypertensives with a poor response to drug therapy. We studied 24 patients, aged between 18 and 65 years, whose blood pressure could not be normalized with a combination of at least two antihypertensive drugs. We found no difference in systolic blood pressure but diastolic blood pressure was significantly (P less than 0.001) lower when measured intra-arterially. The mean difference between the direct and the indirect blood pressure determination was 16.2 +/- 1.5 mmHg (s.e.m.), and the range was 2.3-39.6 mmHg. Age, duration of hypertension and left ventricular hypertrophy was not correlated with the incidence and extent of pseudohypertension. We conclude that in hypertensives with a poor response to drug therapy, blood pressure measurements should be taken intra-arterially in order to avoid the hazards of overtreatment. PMID- 2258790 TI - Dose-response curves in antihypertensive combination therapy: results of a controlled clinical trial. AB - We studied the dose-response relationship for hydrochlorothiazide + triameterene and verapamil, comparing monotherapy with combined treatment in 216 hypertensive patients over 3 weeks of active treatment following a 2-week washout period with placebo. The study was a double-blind, randomly allocated, clinical trial using a two-factorial analysis of variance design. The results showed that the highest dose (a combination of 160 mg verapamil with 25 mg hydrochlorothiazide and 50 mg triameterene) also had the maximum antihypertensive effect. We further conclude that multifactorial trial designs are the most useful designs for analyzing the effects of combination therapy and therefore should be used more often. PMID- 2258791 TI - Insulin resistance and beta-cell hypersecretion in essential hypertension. AB - To determine whether a decreased sensitivity to insulin is involved in the pathogenesis of essential hypertension, fasting blood glucose, serum insulin, serum C peptide, the glucose:insulin ratio and the insulin:C-peptide ratio were measured in 14 lean normotensives, 17 overweight normotensives, 17 lean hypertensives and 20 overweight hypertensives. Compared with the lean normotensives, the patients who were overweight, those with hypertension and those who were both overweight and hypertensive showed increased fasting serum insulin and C-peptide levels, and a lower glucose:insulin ratio. No significant difference between the normotensive and the hypertensive subjects was found in the insulin:C-peptide ratio. Diastolic blood pressure was directly correlated with serum insulin (P less than 0.01) and with C-peptide levels (P less than 0.01), and inversely correlated with the glucose:insulin ratio (P less than 0.02). We conclude that insulin resistance is present in both essential hypertensive and overweight subjects. Since the present study showed that hepatic insulin clearance was normal in hypertensives, the hyperinsulinaemia in essential hypertension appears to be due to beta-cell hypersecretion in response to a defective peripheral action of the hormone. PMID- 2258793 TI - Adherence with pediatric regimens. PMID- 2258792 TI - Issues in adherence with pediatric regimens. AB - Adherence to recommendations for health care is an area of serious concern for pediatric psychologists. The present article highlights several key issues affecting research and clinical work in this area. They include: difficulties defining and measuring adherence; developmental aspects of adherence; special concerns with low income populations; and limitations of intervention research. In addition, several directions for future investigation in the area of pediatric adherence are addressed. PMID- 2258794 TI - Adherence issues in the medical management of asthma. AB - Asthma is a common chronic illness of childhood that requires coordinated efforts by children, families, and health care professionals for proper medical management. The medical management of pediatric asthma involves pharmacological and behavioral recommendations to both prevent and control asthma attacks. However, management of these attacks is hindered by failure to adhere to the prescribed recommendations. While the literature on adherence in pediatric asthma has grown over the past 10 years, few definitive statements can be made about causes and treatment. Various issues related to adherence and pediatric asthma are reviewed in this paper, including assessment methods, factors influencing adherence, and treatment strategies. Recommendations for future research are provided, starting with more controlled randomized studies. PMID- 2258795 TI - Adherence issues in pediatric bone marrow transplantation. AB - The procedure of bone marrow transplantation entails a prolonged, aversive regimen in which adherence problems often develop, particularly with administration of oral antibiotic medications. A retrospective chart review revealed that 52% of pediatric patients evidenced significant adherence problems during the procedure. The highest rates of noncompliance were found in preschool and school-age children, with a surprisingly lower frequency in adolescents. Case summaries are presented to illustrate significant clinical issues and intervention strategies. These are discussed in terms of both their practical and theoretical significance regarding the determinants of adherence behavior. PMID- 2258796 TI - Assessing family sharing of diabetes responsibilities. AB - This study examined sharing of diabetes responsibilities between mothers and their diabetic children and the relationship between patterns of mother-child sharing of responsibility for diabetes tasks and demographic variables, adherence, and metabolic functioning in children with insulin-dependent diabetes mellitus (IDDM). A factor analysis of the Diabetes Family Responsibility Questionnaire (DFRQ), a 17-item questionnaire developed for the present study, resulted in a meaningful three-factor solution. Factors included responsibilities related to regimen tasks, General Health Maintenance, and Social Presentation of Diabetes. Analysis indicated that the DFRQ had adequate internal consistency and concurrent validity. One hundred and twenty-one children with IDDM, 6-21 years of age, and their mothers completed the DFRQ. Glycosylated hemoglobin (HbA1c) was used to index the child's level of metabolic control. Results of multiple regression analyses indicated that the child's age, disease duration, and sex are significant predictors of mother and child patterns of sharing diabetes responsibilities. Disagreements between mothers and children in perceptions of who is assuming responsibility and adherence level were significant predictors of HbA1c. Results indicated that children assume increasing responsibility with increasing age. Clinicians should not assume that mothers and children communicate about the sharing of diabetes responsibilities in the family or about changes in expectations of who is responsible as children develop. To foster better control and adherence in diabetic children, members of the health care team can help to identify diabetes tasks for which no one in the family takes responsibility. PMID- 2258797 TI - Assessing daily diabetes management by 24-hour recall interview: the validity of children's reports. AB - The current investigation examined the accuracy of diabetic children's 24-hr recall data by comparing the 7- to 12-year-old children's reports to direct observations of their behavior. Observers' data evidenced sufficient reliability to serve as an acceptable standard to which the children's 24-hr recall data could be compared. The children exhibited excellent agreement with the observers' data on all measures of the occurrence/nonoccurrence of events, including insulin injections, exercise periods, glucose tests, meal, type and amount of insulin injected. Although somewhat poorer reporters on some behaviors, differences were small. Children underreported most dietary behaviors and some exercise behaviors. PMID- 2258798 TI - Adherence among children and adolescents with insulin-dependent diabetes mellitus over a four-year longitudinal follow-up: I. The influence of patient coping and adjustment. AB - An onset cohort of adolescents and children with insulin-dependent diabetes mellitus was studied over a 4-year period. Individual patient psychosocial and demographic factors were assessed at study inception and used to examine aspects of adherence over the follow-up. We found that initial assessment of patient coping (defense level, adaptive strength, and locus of control) and adjustment at study inception were predictive of the level of patient adherence to diabetic regimen over the 4 years of study. Psychosocial variables predicted adherence outcomes independent of patient age. This was found for three domains of adherence, i.e., diet, insulin adjustment, and metabolic monitoring, and for the composite index derived from the separate adherence scales. Preadolescents (ages 9-12) at study entry were more adherent than patients who were already adolescent (ages 13-16) when diagnosed. Using multiple regression, three factors (age, adjustment, ego defense level) accounted for 47% of the variance in adherence. No factors were predictive of change in adherence during the follow-up. Thus, psychosocial characteristics of diabetic children assessed shortly after diagnosis predicted typical or average adherence over a 4-year period. Identification of such characteristics may be useful in developing strategies for intervention early in the course of illness. PMID- 2258800 TI - Pediatric appointment keeping: improving adherence in a primary care allergy clinic. AB - We evaluated the effects of introducing and discontinuing an intervention designed to improve adherence with scheduled appointments in a pediatric allergy clinic. Five nonadherent and three adherent patients received reminders and incentives for keeping their scheduled appointments. Adherence with appointments increased for three of the five nonadherent children, who had an average increase of 13%, and adherent patients continued to keep appointments during the intervention condition. After 10 scheduled allergy clinic appointments had been kept, incentives were discontinued while reminders continued. Improvements in adherence were not maintained after incentives were discontinued and two children showed reductions in adherence to below-baseline levels. Incentive programs increase appointment keeping, but discontinuing incentives abruptly may result in the return of nonadherence, even when reminders are provided as a maintenance strategy. Future pediatric psychology research and practice should investigate both the benefits and limitations of strategies designed to improve adherence. PMID- 2258801 TI - Cellular adhesion to implanted intraocular lenses. PMID- 2258799 TI - Adherence among children and adolescents with insulin-dependent diabetes mellitus over a four-year longitudinal follow-up: II. Immediate and long-term linkages with the family milieu. AB - Cross-sectional and longitudinal findings drawn from a 4-year longitudinal study of an onset cohort of preadolescents and early adolescents with insulin-dependent diabetes and their families are presented. Patient and parent perceptions of the family environment near the time of diagnosis are used to examine patterns of adherence in the first year of illness as well as over the four follow-up years. We found that family conflict, cohesion, and organization were strongly associated with independently rated first-year adherence levels. The strongest predictor of longer term adherence was family conflict, as experienced by the patients. In addition, parents' and youngsters' perceptions of family cohesion predicted improved adherence as well as overall higher levels of patient adherence. The findings are discussed with respect to the clinical implications of discovering those family characteristics that can, shortly after diagnosis, predict short- and long-term adherence. In addition, we present planned investigations intended to further clarify paths from family perceptions to individual diabetes behaviors. PMID- 2258802 TI - Implantation of scleral-fixated posterior chamber intraocular lenses. AB - A surgical technique for implanting a posterior chamber intraocular lens (IOL) in eyes without capsular or zonular support is presented. A 10-0 polypropylene suture attached to a standard needle is tied to the apex of each haptic and passed transclerally through the ciliary sulcus to secure the haptics at the 3 o'clock and 9 o'clock meridians. This technique produced good visual results in six aphakic patients who were contact lens intolerant, two patients in whom capsular or zonular rupture at the time of cataract surgery precluded standard nonsuture fixation techniques, one patient who had intracapsular cataract extraction for a subluxated, cataractous lens, and one patient who had secondary IOL implantation in combination with penetrating keratoplasty for aphakic bullous keratopathy. Advantages over other techniques of posterior chamber lens implantation in the absence of capsular support include technical ease, avoidance of iris fixation, and more precise placement of scleral fixation sutures, thus minimizing IOL decentration. PMID- 2258803 TI - Explantation of 3M diffractive intraocular lenses. AB - The visual acuity, bifocal capability and quality of vision were evaluated in 14 patients who had implantation of a 3M diffractive posterior chamber intraocular lens (IOL). Initially, four patients had an existing monofocal IOL in the fellow eye as controls. Ten of patients had the unoperated fellow eye as controls. Three of these patients subsequently had monocular IOL implantation, bringing the number of pseudophakic monofocal IOL control eyes to seven. All but two patients noted monocular diplopia; in three patients this was so intolerable that the diffractive lens was explanted and exchanged for a monofocal lens, following which the visual acuity improved by an average of two Snellen lines and complaints of monocular diplopia disappeared. Three patients had bilateral 3M diffractive lens implantation. PMID- 2258804 TI - Contrast sensitivity as a function of focus in patients with the diffractive multifocal intraocular lens. AB - Contrast sensitivity as a function of focus and visual acuity as a function of contrast were investigated in 19 patients with a diffractive multifocal intraocular lens and compared with 19 control patients with a conventional monofocal implant. The contrast sensitivity of the multifocal patients followed a bimodal curve with a maximum sensitivity at the far focus and a second peak at the near focus, corresponding to about +3 diopters in the spectacle plane. The maximum sensitivity of the multifocal group was 0.14 log units lower than the control group (P less than .05). In the near region, the contrast sensitivity of the multifocal patients exceeded that of the control group from +2 diopters and inward. No difference in distance visual acuity was found with high contrast letters. With intermediate contrast letters, the visual acuity of the multifocal patients was lower than that of the control group (P less than .05). PMID- 2258805 TI - Survey of the clinical use of glare and contrast sensitivity testing. AB - In August 1988, we surveyed a random 10% sample of the members of the American Society of Cataract and Refractive Surgery about their use of contrast sensitivity and glare testing. Of 396 surveys mailed, 214 were returned for a response rate of 54.3%. Thirty-six percent of respondents used glare testing alone; 5.6% used contrast sensitivity testing alone; 23.4% used both test modalities; 35% used neither. The most common uses of glare and contrast sensitivity testing were to evaluate visual function in patients who have cataracts, secondary cataracts, and/or intraocular lens problems. PMID- 2258806 TI - Effect of intraocular lens decentration on retinal image contrast. AB - We describe an optical model of the eye that allowed the effect of intraocular lens (IOL) decentration on retinal image contrast to be photographically studied. Decentrations of varying degrees of severity were modeled to correlate the amount of aphakic pupillary area with the contrast of the resulting images as measured by a digital photometer. Image contrast was found to decrease linearly as the proportion of aphakic pupillary area increased. Human clinical correlates are discussed. PMID- 2258807 TI - Comparison of the effect of topical corticosteroids and nonsteroidals on postoperative corneal astigmatism. AB - A controlled study compared the effects of a topical steroid (1% prednisolone acetate) and a topical nonsteroidal anti-inflammatory agent (0.03% flurbiprofen) on postoperative changes in corneal astigmatism in a series of patients having phacoemulsification and posterior chamber lens implantation through a 6.5 mm scleral pocket incision. The incisions were closed with a continuous running 10-0 monofilament nylon suture under tonometric and keratometric control. The results of the study showed that both agents demonstrated similar postsurgical astigmatic decay curves; however, the group receiving the nonsteroidal agent had an earlier decay of iatrogenically induced astigmatism. Approximately 80% of cases receiving the nonsteroidal agent completed the postoperative course without the use of topical steroids, indicating that in some cases steroids may be avoided after cataract removal. PMID- 2258808 TI - Effect of thermokeratoplasty on corneal curvature. AB - A cadaver eye model was used to evaluate and quantify the use of thermokeratoplasty for steepening the central cornea to correct hyperopia. Four groups of eye-bank eyes were treated with four separate surgical plans. Each plan involved the placement of controlled thermal burns (in the depths of the corneal stroma, using a cautery probe) applied in a radial pattern up to a premarked optical zone. The plans differed in the sequence of surgical steps. All plans progressively added radials and applications (to decrease optical zone) in various sequences. Corneal curvature was measured at baseline and at each surgical step. As more surgery was done within each plan, the corneas became progressively steeper. Total mean changes in corneal curvature ranged from 16.26 diopters to 19.76 diopters, depending on the plan. At each optical zone, as the number of radials increased, the effect increased. With progressively smaller optical zone size, the effect also increased. PMID- 2258809 TI - Biconvex intraocular lenses and Nd:YAG capsulotomy: experimental comparison of surface damage with different poly(methyl methacrylate) formulations. AB - Biconvex posterior chamber lenses have optical advantages and decrease the risk of capsular opacification, but they are more likely to be pitted during ND:YAG capsulotomy because of apposition of the lens to the capsule. This study reports the likelihood of surface damage to different formulations of poly(methyl methacrylate) at the energy levels required to open posterior capsules. Molded lenses are more easily damaged than higher molecular weight lathe-cut materials (P less than .01), as expected. However, by keeping energy output low, even injection-molded lenses showed minimal damage, with mean pit size 39 +/- 39 microns at 1 mJ. By using a converging contact lens, low power, and keeping the focus behind the capsule, damage to all materials tested should be clinically insignificant. PMID- 2258810 TI - Anterior chamber depth with sulcus and capsular bag placed IOGEL lenses. AB - The anterior chamber depth was measured in 15 eyes with sulcus placed (Group 1) and 12 eyes with bag placed (Group 2) IOGEL PC-12 lenses, and in 11 eyes with bag placed IOGEL 1103 lenses (Group 3). The mean anterior chamber depth was 3.29 mm in Group 1, 4.17 mm in Group 2, and 4.16 mm in Group 3. The difference between the mean anterior chamber depth with sulcus and bag placed IOGEL PC-12 lenses is statistically significant (P less than .0005). One effect of the different anterior chamber depths was that the anterior surface of a sulcus placed IOGEL lens frequently touched the pupillary border, whereas this rarely occurred when it was placed in the capsular bag. Another effect of differing anterior chamber depths was a different A-constant for the SRK-formula for sulcus or bag placement. In this study it was about 1 diopter greater with bag fixation than with sulcus fixation. It is recommended that each surgeon use specific A constants to enhance the predictability of the postoperative refraction. PMID- 2258811 TI - Conversion of keratometer readings to polar values. AB - Corneal astigmatism is a complex entity that has direction and magnitude. This study reports a new method to describe corneal astigmatism within the with- and against-the-rule concept. Each net astigmatism of the maximal power M in the meridian alpha may be divided into two dioptric components: a with-the-rule astigmatism projected on the 90-degree meridian and an against-the-rule component projected on the 180-degree meridian. The former figure has the dioptric value M X sin2 alpha, the latter M X cos2 alpha. The polar value is defined as the difference between these magnitudes: M X (sin2 alpha - cos2 alpha). The polar value calculates the balance between the with- and against-the-rule components for any given net astigmatism. The entire model allows an exact description of surgically induced with- or against-the-rule astigmatism following cataract extraction. The advantage of the model is that a corneal astigmatism may be expressed by a single figure. The system enables each surgeon to evaluate the contribution of the preoperative astigmatism, incision type, suture technique, and postoperative treatment on the final astigmatism. This in turn allows the surgeon to estimate a number of different surgical techniques empirically. By disposing of and choosing between several known techniques the surgeon may be able to minimize final astigmatism even in cases of significant preoperative astigmatism. PMID- 2258812 TI - Comparison of the cellular response on intraocular lenses implanted in rabbit eyes with and without extracapsular lens extraction. AB - Three-piece poly(methyl methacrylate) intraocular lenses (IOLs) were implanted in rabbit eyes with and without lens extraction to examine the cellular response on the IOL surface without the effects of the residual lens cortex. Each rabbit had extracapsular lens extraction (ECCE) with IOL implantation in the posterior chamber of one eye. In the second eye, the IOL was implanted in the anterior chamber without lens extraction. The lenses were removed and studied with light microscopy and scanning electron microscopy one week after surgery. Light microscopic findings revealed a similar cellular response on the surface of the IOLs in both groups. Scanning electron microscopy suggested that the cellular adhesiveness on the IOL surface in the eyes without lens extraction was weaker than in the eyes that had ECCE. Cells on the IOLs in the eyes without lens extraction were flatter and had membranous pseudopodia. It appears that the cells on the IOL surface were caused by a foreign body reaction and that their adhesiveness to the IOL was affected by residual lens cortex. PMID- 2258813 TI - Cellular reaction on the surface of intraocular lenses removed from human eyes. AB - We studied four angle-supported anterior chamber lenses whose optics and haptics were made of poly(methyl methacrylate). All four lenses had been removed from human eyes because of bullous keratopathy. Using light and electron microscopy, we compared the cellular reaction on the optics, which had been in the anterior chamber, with that on the haptics, which had been in touch with the iris stroma. A typical foreign body granuloma was seen around the haptics, while the optics were free of foreign body reaction. PMID- 2258814 TI - Suture-wick endophthalmitis with sutured posterior chamber intraocular lenses. AB - A patient had a corneal transplant with removal of an anterior chamber lens. As part of the procedure, an exchange posterior chamber lens was inserted and sutured transsclerally into the ciliary sulcus with two subconjunctival 10-0 polypropylene (Prolene) sutures. One month later the patient experienced a sudden decrease in vision and severe eye pain. Streptococcus viridans was cultured from the vitreous tap and the eye eventually was lost from this endophthalmitis. The infecting organism appeared to gain access to the eye through one of the Prolene sutures that had eroded through the conjunctiva and become exteriorized. This report presents a case in which an eroding 10-0 Prolene suture used for transscleral posterior chamber lens fixation was the probable mechanism causing endophthalmitis. This complication represents an avoidable risk unique to this type of intraocular lens fixation. PMID- 2258815 TI - Endocapsular phacoemulsification following buttonhole anterior capsulotomy: a preliminary report. AB - New techniques for anterior capsulotomy and phacoemulsification in endocapsular cataract surgery are introduced. Microcircular capsulotomy using a micropunch at both ends of a linear capsular opening prevents enlargement by tearing because of a reduction of stress concentration in the region. An ultrasound-operated irrigation/aspiration tip made of titanium facilitates the removal of the remaining nuclear disc after removal of the hard nuclear core, thus reducing the risk of posterior capsular rupture during phacoemulsification. Our technique may improve the prospect of endocapsular procedures. PMID- 2258816 TI - One-step forceps for capsulorhexis. AB - There are several popular methods for creating a continuous-tear capsulotomy, or capsulorhexis, which usually involve several instruments and steps. This report describes a new forceps for capsulorhexis that can be used to open the capsule and complete the circular tear in one step. Its unique features are its small size, shortened length, thin, rounded blades with cystotome-type tips for opening the capsule, and round handles for manipulation ease. PMID- 2258817 TI - Consultation section. Retrobulbar hemorrhage. PMID- 2258818 TI - Evaluating multifocal intraocular lenses. PMID- 2258819 TI - Noncicatricial oval deformation of the pupil induced by one-piece poly(methyl methacrylate) posterior chamber lenses. PMID- 2258820 TI - Complication after cryo therapy. PMID- 2258821 TI - Use of soft lenses. PMID- 2258822 TI - Chevron incision for cataract surgery. PMID- 2258823 TI - [Expectation and hopes for the Physiological Society of Japan]. PMID- 2258824 TI - V International Conference on Biology and Pathogenicity of Free Living Amoeba. Brussels, Belgium, August 7-11, 1989. Proceedings. PMID- 2258825 TI - NACM, a cytopathogenic protein from Naegleria gruberi, EGs; purification, production of monoclonal antibody, and the immunoidentification of a product that develops in NACM-treated vertebrate cell cultures. AB - The story of NACM involves the discovery of a deleterious response of cultured vertebrate cells to a component in cell-free lysates prepared from free-living amebae of the genus Naegleria; hence the acronym NACM derived from Naegleria ameba cytopathogenic material. The cellular reaction is the basis for the biological assay that has been fundamental in the study of the action of NACM in a variety of cell cultures. It also has been used in the determination of the physical characteristics, and to monitor the behavior of NACM during isolation procedures. All findings are compatable with the conclusion that NACM is a 35 Kd protein. Recently, the use of monoclonal antibodies (MAbs) prepared to amebae derived purified NACM have resulted in the visual display of a product that develops exclusively in NACM-treated cells. That cellular product is shown to be related to NACM by its immunostaining reaction with the MAb; the relationship of the MAb with NACM is demonstrated by its ability to neutralize the biological activity of NACM, and as an immunostain, to react with purified fractions of NACM and with whole amebae. The combination of these observations describes a unique set of interactions in which NACM, an amebic component, identified as a protein, has characteristics of an infectious agent when introduced into cultures of avian and mammalian cells. PMID- 2258826 TI - Genome structure and evolution of Naegleria and its relatives. AB - In the 4 yr since the molecular biology of DNA in Naegleria was last reviewed several major advances have been made, and these are reviewed here: isolation and characterization of mitochondrial and ribosomal DNAs; enumeration of chromosomal DNAs by pulsed field gel electrophoresis; sequence analysis of differentially expressed genes; phylogenetic placement of the genus Naegleria among the eukaryotes and Naegleria species within the genus. PMID- 2258828 TI - Conjugation involving dividing cells of Tetrahymena thermophila. AB - Feulgen-stained preparations of mixtures of starved Tetrahymena thermophila cells of complementary mating types have revealed an atypical form of conjugation involving cells which have completed the nuclear events of cell division, but have not undergone cytokinesis. Both micronuclei in the dividing cells are induced to undergo meiosis, but in 21 of 23 cases, the anterior micronucleus was activated 1st, suggesting that the meiotic inducer is synthesized near the mating junction and diffuses posteriad. Despite the induction of two micronuclei, "triad" conjugants appear to regulate nuclear events so as to produce a normal outcome. PMID- 2258827 TI - Epidemiology of free-living ameba infections. AB - Small free-living amebas belonging to the genera Acanthamoeba and Naegleria occur world-wide. They have been isolated from a variety of habitats including fresh water, thermal discharges of power plants, soil, sewage and also from the nose and throats of patients with respiratory illness as well as healthy persons. Although the true incidence of human infections with these amebas is not known, it is believed that as many as 200 cases of central nervous system infections due to these amebas have occurred worldwide. A majority (144) of these cases have been due to Naegleria fowleri which causes an acute, fulminating disease, primary amebic meningoencephalitis. The remaining 56 cases have been reported as due either to Acanthamoeba or some other free-living ameba which causes a subacute and/or chronic infection called granulomatous amebic encephalitis (GAE). Acanthamoeba, in addition to causing GAE, also causes nonfatal, but nevertheless painful, vision-threatening infections of the human cornea, Acanthamoeba keratitis. Infections due to Acanthamoeba have also been reported in a variety of animals. These observations, together with the fact that Acanthamoeba spp., Naegleria fowleri, and Hartmannella sp. can harbor pathogenic microorganisms such as Legionella and or mycobacteria indicate the public health importance of these amebas. PMID- 2258829 TI - Changes in the shape of Leishmania major promastigotes in response to hexoses, proline, and hypo-osmotic stress. AB - Leishmania major promastigotes in late-log phase are generally long and slender, and remain so during a 1 h incubation in buffer without exogenous substrate. When glucose, 2-deoxyglucose, fructose, mannose, or proline are added, the cells become shorter and more rounded. The shape change in response to glucose is complete within 20 min and is reversible upon incubating the cells without substrate. Galactose, 3-O-methylglucose, 6-deoxyglucose, sucrose, maltose, ribose, glycerol, alanine, glutamate or aspartate do not cause the shape change. Decreasing the osmolarity of the medium causes a rounding of the cells similar to that observed in the presence of glucose, and increasing the osmolarity inhibits the shape change in response to glucose. Inhibitors of glucose transport and 2nd messenger analogs do not affect the shape change. PMID- 2258830 TI - Regulation of ornithine decarboxylase activity in the growth cycle of Tetrahymena thermophila. AB - Cells of the ciliated protozoan Tetrahymena thermophila, grown in proteose peptone medium up to late logarithmic phase, harvested by centrifugation, and resuspended in fresh medium to almost the same cell density, underwent one more division cycle within 5 h after inoculation, thereafter being definitely in full stationary phase. This growth cycle proved to be a useful tool to investigate the activation and deactivation of ornithine decarboxylase ODC1 in Tetrahymena: In late logarithmic phase the cells contained a very low specific activity of ODC of about 3 nmol CO2.h-1.mg-1 in the soluble protein fraction. After growth stimulation the activity was increased up to 100-fold within 1 h. This high activity was maintained for about 5 h-about as long as division activity-then rapidly declined with a half life time (t1/2) of about 15 min to the original low level. Inhibition assays with cycloheximide and actinomycin D revealed that: i. the rapid increase of ODC activity was biphasic with one component of translation of preexisting mRNA and one component of translation of newly transcribed mRNA; ii. the t1/2 of the mRNA of ODC was estimated to be about 2 h; iii. inhibition of protein biosynthesis before ODC inactivation at 5 h caused a decrease of ODC with a t1/2 of 55 min instead of 15 min. These findings suggest that ODC activity in Tetrahymena is regulated on both levels: transcription and translation and by an inactivating protein factor which is regulated at the level of biosynthesis. PMID- 2258831 TI - Leishmania donovani: a chemically defined medium suitable for cultivation and cloning of promastigotes and transformation of amastigotes to to promastigotes. AB - A chemically defined medium using commercially available alpha-MEM supplemented with hemin, HEPES, L-glutamine, D-glucose, folic acid, D-biotin and adenine supports the luxuriant growth and propagation of Leishmania donovani promastigotes. A peak parasite population of about 7.0 x 10(7)/ml at stationary phase and a population doubling time of 11.4 h for high-subpassage promastigotes were obtained. The medium was suitable for transformation of isolated amastigotes from infected hamster spleen. Promastigotes could be detected by culturing kala azar patients' bone-marrow aspirate or spleen puncture material in this medium. Four out of six freshly transformed isolates gradually adapted and grew well in this medium. Macroscopic colonies appeared on agar plates prepared with the medium within 16-20 days after inoculation. The cloning efficiency was increased about five-fold by glycerol supplementation. PMID- 2258832 TI - Effect of gossypol on trypomastigotes and amastigotes of Trypanosoma cruzi. AB - Bloodstream Trypanosoma cruzi trypomastigotes isolated from infected mice undergo reduction of motility and structural damages after 5 to 45 min exposure to gossypol at concentrations ranging from 5 to 50 microM. When 1% serum albumin is added to the incubation medium, no alterations of parasites are observed, even with 100 microM gossypol. Intracellular T. cruzi amastigotes in infected Vero cell cultures exposed to 5 microM gossypol for 2 h do not show changes. Incubation with 5 microM gossypol for 48 h produces complete disruption of host cells; however, the amastigotes they contain show only minor alterations. The observations indicate that, in protein-rich media, gossypol is complexed into associations which have no activity on the different forms of the T. cruzi biological cycle. PMID- 2258833 TI - Amoeboid locomotion of Naegleria gruberi: the effects of cytochalasin B on cell substratum interactions and motile behavior. AB - The major manifestations of amoeboid locomotion in Naegleria-cytoplasmic streaming, pseudopod production, cell polarity and focal contact production require that the actin-based cytoskeleton be extremely dynamic. Whether these features are causally linked is unclear. In an attempt to answer this question we have used the fungal product cytochalasin B (cyt B) to dissect the motility process. This drug can perturb the organisation of actin filaments both in vivo and in vitro. Essentially cyt B acts as a molecule which can cap the barbed ends of actin filaments. Not surprisingly, therefore cyt B has an effect on rates of actin polymerization and the dynamic state of actin in the cytoplasm. We have found that cyt B has a profound effect on focal contact production and breakdown. Within minutes of addition of cyt B focal contact production ceases, existing focal contacts are stabilised but cytoplasmic streaming and pseudopod production are not blocked. In conclusion it is now clear that the state of actin required for focal contact production is different from that required for pseudopod extension and cytoplasmic streaming. PMID- 2258834 TI - Segmental specialization of neuronal connectivity in the leech. AB - 1. Every segmental ganglion of the leech Hirudo medicinalis contains two serotonergic Retzius cells. However, Retzius cells in the two segmental ganglia associated with reproductive function are morphologically distinct from Retzius cells elsewhere. This suggested that these Retzius cells might be physiologically distinct as well. 2. The degree of electrical coupling between Retzius cells distinguishes the reproductive Retzius cells; all Retzius cells are coupled in a non-rectifying manner, but reproductive Retzius cells are less strongly coupled. 3. Retzius cells in standard ganglia depolarize following swim motor pattern initiation or mechanosensory stimulation while Retzius cells in reproductive ganglia either do not respond or hyperpolarize. 4. In standard Retzius cells the depolarizing response caused by pressure mechanosensory neurons has fixed latency and one-to-one correspondence between the mechanosensory neuron action potentials and Retzius cell EPSPs. However, the latency is longer than for most known monosynaptic connections in the leech. 5. Raising the concentration of divalent cations in the bathing solution to increase thresholds abolishes the mechanosensory neuron-evoked EPSP in standard Retzius cells. This suggests that generation of action potentials in an interneuron is required for production of the EPSP, and therefore that the pathway from mechanosensory neuron to Retzius cell is polysynaptic. 6. P cells in reproductive segments have opposite effects on reproductive Retzius cells and standard Retzius cells in adjacent ganglia. Thus the difference in the pathway from P to Retzius is not localized specifically in the P cell, but elsewhere in the pathway, possibly in the type of receptor expressed by the Retzius cells. PMID- 2258835 TI - Seasonal variation of serotonin content and nonassociative learning of swim induction in the leech Hirudo medicinalis. AB - It is possible to obtain habituation of swim induction by stimulating the leech with repetitive light electrical trains. After obtaining this simple form of non associative learning, it is also possible to potentiate its response by a series of nociceptive skin brushings (dishabituation). Serotonin applied to the animal is the only neurotransmitter found to mimick dishabituation. We have observed that in the period April-June most animals did not exhibit potentiation of the swimming response after nociceptive stimulation while injection of serotonin mimicked dishabituation as in the animals treated in the period October-March. We have seen correlation between the changes in nonassociative learning and the seasonal variation of serotonin levels in segmental ganglia. This finding strengthens the hypothesis of serotonin as the neurotransmitter mediating dishabituation in swim induction of the leech. PMID- 2258836 TI - Local anesthetic action of phentolamine on insect mechanoreceptors. AB - 1. The effect of phentolamine on the response properties of insect mechanoreceptors and on the conduction in their axons was examined using electrophysiological techniques. 2. Phentolamine blocked conduction of action potentials along axons, an effect which exhibited 3 characteristics typical of local anesthetics: the effect was frequency-dependent, reversible and varied for nerves with different diameters. 3. The concentration of phentolamine required to block axonal conduction (1-2 x 10(-3) M) was significantly higher than that required to abolish the response of receptors to mechanical stimulation (3-5 x 10(-4) M). 4. All mechanoreceptors that were examined in Locusta migratoria and Periplaneta americana were inactivated by phentolamine (Table 1). The type I receptors (chordotonal, campaniform and hair sensilla) were inactivated within 5 15 min following phentolamine application. The only type II receptor examined (forewing stretch-receptor) underwent a phase of repetitive discharge before being inactivated. 5. Tolazoline and metoclopramide inactivated, like phentolamine, mechanoreceptors at lower concentrations than necessary to block axonal conduction. However, yohimbine and chlorpromazine inactivated mechanoreceptors and blocked axonal conduction at similar concentrations. 6. These findings suggest that phentolamine affects sense-organ specific ionic processes that are more sensitive to the drug than the ionic processes along the axons. PMID- 2258837 TI - Clinicians and information technology. PMID- 2258838 TI - Black looks ... at a black act. PMID- 2258840 TI - A paediatrician visits San Francisco. PMID- 2258839 TI - Osteoarthritis. A review. PMID- 2258841 TI - Physicians' attitudes to the treatment of elevated serum cholesterol. AB - A questionnaire was sent to 457 physicians (328 general practitioners, 129 hospital doctors) to assess their attitudes to and their knowledge and practice of the management of raised serum cholesterol. Replies were returned by 206 (63%) general practitioners and 95 (74%) hospital doctors. While smoking, hypertension, diabetes mellitus and elevated total serum cholesterol were recognised as major risk factors for coronary heart disease, a significant number of respondents considered serum triglycerides to be less important. Both groups of physicians start dietary management at similar total serum cholesterol levels, but hospital doctors were more likely to use dietetic services. The two groups had a similar threshold for the addition of drug therapy. A bile acid sequestrant was the favoured first choice as a cholesterol lowering agent, although a wide variety of other drugs were also chosen. The screening of high risk patients was preferred to whole population and opportunistic screening for identifying hypercholesterolaemic individuals. The findings have important implications in the delivery of services to hypercholesterolaemic patients. PMID- 2258842 TI - The use of radiotelemetry after discharge from the coronary care unit. AB - Forty-six of 110 consecutive admissions to the coronary care unit (CCU) were monitored by telemetry after discharge from the unit. One of three patients with sudden cardiac death was resuscitated successfully and four patients developed atrial fibrillation which resulted in investigation by echocardiography and treatment with anticoagulants. Significant ventricular ectopic activity was detected in four other patients. Arbitrary selection of patients resulted in those with complicated courses in the CCU being more likely to be monitored by telemetry after transfer to the ward than those which were uncomplicated. There were no cases of sudden cardiac death in patients who did not have telemetry. The cost of telemetry was 2,775 pounds per system. All 19 districts in the North-West region of the UK responded to a questionnaire. Five of the 19 used telemetry but only two of these used the technique routinely after discharge from the CCU whereas four used radiotelemetry to monitor patients on the ward when coronary care beds were unavailable. Eight districts wanted telemetry but needed funds. We conclude that radiotelemetry is an inexpensive way to detect serious arrhythmias in patients transferred from the CCU to the general ward. Monitored from the CCU, cardiac arrest can be immediately detected and treated by experienced staff. Asymptomatic atrial fibrillation leads to prompt investigation by echocardiography and possible treatment with anticoagulants. The importance of noticing major ventricular ectopic activity is likely to increase with the possibility of selecting patients with a high risk of life-endangering arrhythmias so that antiarrhythmic drugs or techniques such as automatic defibrillators can be used appropriately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258843 TI - Self-harm patients not admitted to hospital. AB - In recent years a large proportion of self-harm patients attending hospital have not been admitted to medical or short-stay wards but have returned home directly from accident and emergency departments. A continued trend towards such a policy seems likely despite limited and conflicting evidence on its desirability. The clinical, training and epidemiological implications of changes in self-harm admission policy are outlined, together with recommendations concerning clinical audit. PMID- 2258844 TI - Clinical versus biochemical assessment in thyroxine replacement therapy: a retrospective study. AB - A retrospective audit of a thyroid clinic revealed that only 67% of clinical assessments of thyroid status in patients receiving thyroxine replacement therapy were correct. The identification of patients on excessive doses of thyroxine appears to be the most difficult by clinical assessment alone, only 10% of those patients with a suppressed TSH level being identified. This study emphasises the importance of thyroid function tests in the assessment of patients on thyroxine replacement. PMID- 2258846 TI - Impact of the European community on medicine. Report of a conference. PMID- 2258845 TI - Clinical outcome following coronary balloon angioplasty in 100 consecutive patients with multivessel coronary artery disease. AB - Prompted by current uncertainties regarding the precise role of percutaneous transluminal coronary balloon angioplasty (PTCA) in patients with multivessel disease, we reviewed the records of 100 such patients undergoing their first PTCA at our centre between 1 March 1987 and 23 March 1989. Thirty had three-vessel coronary disease (stenoses greater than or equal to 70% in all three major coronary artery territories), 51 had a previous myocardial infarction and 25 had undergone previous coronary bypass surgery. The mean number of lesions of greater than or equal to 70% per patient was 2.7 (0.8) [mean (SD)]. Successful angioplasty was achieved in 88 of these 100 patients. One year following successful angioplasty, the overall event-free rate [freedom from death, myocardial infarction, need for further revascularisation by either aortocoronary bypass graft surgery or repeat angioplasty, and recurrence of severe (class III/IV) angina] was 73%. These data suggest that, in patients with multivessel disease, angioplasty may be an effective technique for short-term symptomatic management. Definitive guidelines regarding the role of PTCA in such patients must await the results of ongoing large-scale clinical trials. PMID- 2258847 TI - Design, development and decline of a medicine. Report of a conference. PMID- 2258848 TI - Mediator and cellular mechanisms in asthma. The Philip Ellman lecture 1990. PMID- 2258849 TI - Interfaces in medicine: asthma. Report of a conference. PMID- 2258850 TI - The stethoscope--Laennec's misnomer. PMID- 2258851 TI - Doctors and historians. The Osler Oration 1990. PMID- 2258852 TI - Arab medicine. PMID- 2258854 TI - Are more consultants needed for dermatology? PMID- 2258853 TI - The new dermatology. PMID- 2258855 TI - Training in infectious diseases. PMID- 2258856 TI - Communication of autopsy results. PMID- 2258857 TI - Hypertension control and management in Slovenia, Yugoslavia. AB - Data were collected from 413 questionnaires sent to general practitioners throughout Slovenia, accounting for half the physicians in this discipline. BP was measured most commonly in the sitting position (72%), mostly on the left arm. Most respondents (93%) used only one cuff size. Correction of BP readings according to the patient's arm circumference was used by 63% of the respondents. Seventy-eight percent of the general practitioners recorded phase V of the Korotkoff sounds for diastolic BP. BP was measured more than once at each examination by 55%. BP measurements were performed by nurses in 27% of cases. Mercury sphygmomanometers were used by 87%. Manometers were calibrated once a year by 73%. Complete diagnostic procedures for the definition of hypertension were conducted in approximately 50% of patients, predominantly in severe cases. Drug treatment was commenced in the range of 'mild hypertension' usually by 93% of the general practitioners. It was started at BP values of 165/99 mmHg and higher. In patients with other risk factors, it was instituted even earlier. General measures (non-drug therapy) were advised by only 30%. Beta-blockers were usually prescribed to younger patients as drug of choice (74%), and diuretic agents to the elderly (48%). General practitioners' sources of new information about hypertension were mainly medical literature, pharmaceutical industry information, and professional meetings. Prevalence of hypertensive BP values in the responding general practitioners themselves was 8%. PMID- 2258858 TI - Detection, treatment and control of hypertension in Spain. AB - Attitudes and practices with regard to hypertension were the subject of a survey conducted in 1987 among 2,500 Spanish general practitioners. Their responses showed almost complete use of diagnostic criteria adhering to WHO recommendations and guidelines, the wide prescription of diuretics as first-step medication and beta-blockers as the drug of choice in second-step treatment, and a non compliance rate of 25% attributed to inadequate information and bureaucracy, similar to other countries. PMID- 2258859 TI - Ecological association between hypertension and stroke in Catalonia (Spain): development and use of an ecological regression model. AB - The objectives of this paper were to study the association between the prevalence of uncontrolled hypertension (PUHT) and stroke mortality at the ecological level, in nine geographical areas of Catalonia (Spain); to develop an ecological regression model and to assess its ability to predict crude stroke mortality rate (CMR) from the PUHT. The regression equation obtained for the population older than 25 yrs was CSMR x 10(3) = 0.67035 + 4.94752 PUTH x 10(-2). The ecological risk ratio was 8.38 and the ecological attributable proportion 71.1%. The CSMR estimation obtained by applying the model in a concrete case was close to that observed. The results support an ecological association between the studied variables. The ecological model can be useful in the assessment of observed changes in health problems and risk factor levels in the community. It could also be used in the evaluation of intervention programmes. PMID- 2258860 TI - Aggregation of blood pressure in families: genetic and environmental influences. AB - A study was undertaken to determine whether parent-child blood pressure (BP) resemblances reflect parent-child similarities in body build. Those studied were 889 children, 5-18 years old, their parents and relatives because of recognized correlations between body build and BP in individuals, along with familial clustering of these variables. To maximize the likelihood of demonstrating correlations between BP and body build in family members, BP and anthropometric variables of parents whose children were in the upper quintile (group I) and lower quintile (group II) of the same variables were compared. Variance analysis has shown that group I children were heavier (P less than or equal to 0.001) and more obese (P less than or equal to 0.01) than group II. The parents of group I had higher systolic BP (P less than or equal to 0.001), diastolic BP (P less than or equal to 0.01), were taller (P less than or equal to 0.0001), heavier (P less than or equal to 0.001) and more obese (P less than or equal to 0.01), than the parents of group II. Parent-children BP resemblances reflect parent-children similarities in body build. The study of group I children and their families may give important information about determinants of high BP in children. PMID- 2258861 TI - Genetic polymorphism of Na-K cotransport in essential hypertension. AB - Erythrocyte Na-K cotransport is high and genetically correlated to hypertension in Milan hypertensive strain (MHS) rats. In man there is a substantial overlap of individual values between essential hypertensives and controls. However, the findings in rat strains with different types of genetic hypertension suggest that Na-K cotransport studies may throw light on the different pathogenetic mechanisms of the human disease. In 28 normotensive and 22 hypertensive families the midparent-offspring correlation of Na-K cotransport values was significant only in hypertensive families (r = 0.48) and not significant in normotensive ones (r = 0.06), indicating genetic polymorphism for its phenotypic expression only in the hypertensives. In 189 essential hypertensives and 109 normotensives carefully selected from a population-based screening in order to exclude uneven sampling bias, analysis for the bimodality of the distribution of Na-K cotransport clearly showed that normotensives are distributed unimodally and hypertensives bimodally, with nadir of the distributions at about 450 mumols (1 RBC/h). Dividing the hypertensives according to Na-K cotransport value, the high Na-K cotransport subgroup has lower fractional percent excretion of uric acid and plasma renin activity. These data suggest that the high Na-K cotransport subgroup has peculiar characteristics of greater proximal tubular reabsorption (lower fractional excretion of uric acid) that may cause body volume expansion (lower plasma renin activity). PMID- 2258862 TI - Quality of life of patients receiving antihypertensive treatment. AB - Ninety-four hypertensive patients, 52 females and 42 males, 38 to 79 years old, were investigated for quality of life under antihypertensive treatment, using a self-administered questionnaire. Their social situation, work and leisure activities and hypertension-related symptoms were evaluated when first diagnosed and after treatment with antihypertensive drugs. Of the 94 patients, 85 (90%) felt uneasiness due to hypertension, 21 (22%) felt their work was limited, and 27 (29%) reported restricted leisure activities due to hypertension. Eighteen patients (19%) had sexual problems. Females who were severely hypertensive at first visit (mean BP greater than or equal to 120 mmHg), those who were well controlled by treatment (mean BP at last visit less than 105 mmHg), and those whose mean BP decreased markedly (decrease in mean BP greater than or equal to 20 mmHg) showed significant improvement in hypertension-related symptoms. Side effects varied depending on the antihypertensive drug used. It is recommended that the quality of life of patients be taken into consideration when choosing antihypertensive drugs. PMID- 2258863 TI - The impact of a planned health education approach on the control of hypertension in a high risk population. AB - This paper reports on the effectiveness of a planned health education programme on enhancing the control of hypertension in a community demonstrating the highest rates of high blood pressure, cerebrovascular disease, and diseases of the heart in the State of Maryland. Within the community intervention programme, a specific focus was directed at younger black males (ages 18-49) who demonstrated the lowest rates of awareness, treatment, and control for their hypertension, as compared to all other age/race/sex groups. The programme consisted of targeted screenings, outreach, and follow-up; influencing specific health beliefs regarding diagnosis and treatment; and family and community support strategies. Formally trained community health workers provided educational counselling, monitoring, outreach and follow-up services in coordination with a community-wide health provider task force. Results to date indicate that this planned health education approach has been successful in significantly improving the control of hypertension in a high-risk population. PMID- 2258864 TI - Comparison of hypertension treatment on and off the worksite. AB - A survey was carried out in two plants in Haifa, Israel on the prevalence of treated and controlled hypertension. In both plants hypertension treatment was being carried out by family physicians at regular family clinics. In factory A, after screening, a programme of follow-up and treatment by the plant doctor and nurse was introduced. In factory B all hypertensives continued to be referred to their family physician for treatment and follow-up. One year later all previously detected hypertensives were reassessed. The percentage of treated hypertensives had increased from 70.9% to 100% in factory A, and from 55.0% to 62.1% in factory B. The percentage of controlled hypertensives among those treated had increased from 52.7% to 83.7% in factory A, and from 28.0% to 38.9% in factory B. Thus, the percentage of all hypertensives who were controlled increased from 37.3% to 83.7% in Factory A and from 15.4% to 24.1% in Factory B. The introduction of on-site treatment and follow-up of hypertension by a doctor-nurse team was associated with marked improvement of all aspects of hypertensive care. PMID- 2258865 TI - Hypertension: a survey of 7000 Air France employees. AB - During a period of one year, 6,863 employees underwent routine medical check-ups: 3,223 ground staff, 3,129 cabin staff, and 511 cockpit crew. One hundred and fifty permanent hypertensives were recorded and their status and evolution analysed in a survey. For every patient data were collected on illness, treatment, heredity, aetiology, risk factors, type of work and life style. The 150 patients surveyed were divided into four groups: (A) 70 satisfactorily treated hypertensives (57 men, 13 women); (B) 31 unsatisfactorily treated hypertensives (24 men, 7 women); (C) 33 neglected hypertensives (31 men, 2 women); and (D) 16 newly discovered hypertensives (14 men, 2 women). The incidence of hypertension was higher in ground staff (3.9%) than in cockpit crew (1.76%) and very low in cabin staff (0.41%). The neglected and unsatisfactorily treated hypertensives showed a clear improvement in their blood pressure through ongoing surveillance. In conclusion, while the incidence of hypertension in the population surveyed is quite low, this study shows a significantly lower rate in cabin staff and a large proportion of neglected and unsatisfactorily treated hypertension. It also shows how an occupational medical practitioner with no power of prescription can be effective in detecting the disease and referring the employee to his general practitioner, with a view towards achieving better collaboration. PMID- 2258866 TI - Screening for hypertension by volunteers in a middle-class community. AB - Screening for hypertension in citizens 30-69 years of age by trained volunteers was initiated by the community of a middle-class town in Holland. At the same time counselling on cardiovascular risk factors was offered to the public. The campaign ran smoothly and at low cost, resulting in 4% hypertensives detected. The population appeared to be well-informed about cardiovascular risk factors in general, but were ignorant of prevailing personal risk factors. Review of results after one and two years shows that a considerable number of identified patients are lost to follow-up in primary health care. It is concluded that an integrated approach for anticipatory care is required for both screening and patient management by primary health care teams. PMID- 2258867 TI - Groningen Hypertension Service: ten years experience in detecting and treating hypertension in a population of 23,340 persons in rural and urban districts in Holland with a special hypertension service. AB - The Groningen Hypertension Service (GHS) has demonstrated that provision of training for volunteers, technical assistance and the services of the General Practitioner Laboratory (a private foundation offering laboratory and diagnostic facilities) have enabled large rural and urban districts to be screened for hypertension within a short period of time at low cost. The GHS trained volunteers and paramedics, who assisted with the treatment for six months. The General Practitioner Laboratory evaluated treatment in nearly 600 hypertensive patients, leading to the institution of low-dose therapy and careful investigation of side-effects. PMID- 2258868 TI - Self-screening of blood pressure and sodium in a 24-hour urine sample as part of a school health programme. AB - A study was conducted to determine the usefulness of self-screening of blood pressure in families as part of a school health care programme, and to study the relationship between BP and sodium excretion in school children. In 750 families with 10-13 year old children, the mothers were instructed to take BP measurements on themselves, their child and the father whilst at home. A comparison of the children's BP measurements at home and at school with those of the parents showed the home measurements to have the closest correlation with parental BP. Twenty four hour sodium excretion and sodium/potassium ratio in children of borderline hypertensive mothers were positively related to children's BP. PMID- 2258869 TI - Long-term study of borderline hypertension among male industrial workers. AB - Out of 1,236 men aged 40-59 years working in the same industrial plant, 253 (20.5%) had borderline arterial hypertension (BH). These employees and 237 matched normotensives were followed for several years. After 13 years, 343 participants, 70% of the initial number were studied. Arterial hypertension developed in 79.1% of the group with initial BH, most frequently in those with systolic-diastolic, and less often with systolic or diastolic BH. In normotensives, hypertension was diagnosed in 30.0% (P less than 0.001). All participants showed a correlation between blood pressure rise and initial value. A smaller number of men in the group with initial BH (36%) continued to work compared with normotensive men (48.1%) (P less than 0.01). The relationship between ability to work and blood pressure level became more prominent when we took into account final diagnosis: 65.7% of the actual normotensives, 56.4% of the borderline hypertensives and 47.5% of the hypertensives were still working after 13 years. Death rate was also higher in the group with BH (15.4%) than in the controls (8.4%) (P less than 0.01). The highest death rate was found when BH was combined with other coronary risk factors. PMID- 2258870 TI - Blood pressure and other risk factors of cardiovascular disease in two communities with different socio-economic statuses: the Athens study. AB - Blood pressure and other risk factors of cardiovascular diseases were studied in two rural communities of 631 adults (greater than or equal to 18 years old) with different socio-economic statuses, populations A and B. Population A (n = 381) lived in a tourist village on an island, and population B (n = 250) in a remote mountain village. The socio-economic status of population A had improved considerably over the last decade but the physical environment, habits, culture and way of life had been disrupted. Blood pressure, prevalence of hypertension and other risk factors were higher than in population B where socio-economic status was lower but where there had been no disruption of the environment, traditional habits, culture or way of life. These findings might be due to the lack of preventive medicine services in the community. PMID- 2258871 TI - A screening programme for hypertension in general practice. AB - It is recommended that hypertensive patients with a diastolic blood pressure of 100 mmHg be treated. However, it has been proposed that only 50% of hypertensives are diagnosed, and of these, 50% are not treated. We therefore set out to identify hypertensive patients in our practice, who were then actively treated, some in a clinical trial of ketanserin. Of the 3,384 patients (1,667 males and 2,707 females) who were invited to our surgery for a blood pressure measurement, 2,606 patients (77%) attended. The overall prevalence of hypertension in the patients, aged 35-65 years was 2.9%. This prevalence increased with age: from 1.0% in the 35-44 year age group to 3.5% at 45-54 years, and 4.4% at 55-64 years. The mean systolic but not diastolic blood pressure increased with age. There were more male hypertensives than females, except over 55 years of age. Of the 84 hypertensives identified after one visit, the majority remained hypertensive after an additional visit, and 31 agreed to participate in a clinical trial. After a four-week placebo run-in, 22 patients had a diastolic blood pressure above 95 mmHg and were randomly allocated to receive ketanserin 40 mg twice daily or metoprolol 100 mg twice daily. Treatment continued double-blind for three months. There were no significant differences in blood pressure reduction between the treatment groups. The heart rate was reduced more by metoprolol. There were no withdrawals for side effects and no major differences in subjective complaints between the two treatment groups. PMID- 2258872 TI - Treatment of mild hypertension in primary health care: results of a physicians' inquiry, Stuttgart, 1986. AB - One of the most widely discussed problems in the field of hypertension is the treatment of mild hypertension: 90-104 mmHg diastolic BP. Organizations like the WHO recommend caution with respect to drug therapy. To investigate the actual treatment of hypertension by primary health care services, a standardised questionnaire, based on the study protocol of the WHO-coordinated HYRAP project, was sent to all private practitioners, internists and gynaecologists in private practice in Stuttgart in 1986 (n = 480). The response rate among the general practitioners and internists was 68%. The data indicate that a major part of the physicians favour treatment by health counselling. In contrast, the vast majority (89%) of the physicians report treating mild hypertension exclusively by drug therapy. This wide use of drug therapy may be due to the influence of certain reference groups and the health care system itself. The results support recommendations that special attention be given to the training of physicians in health counselling. PMID- 2258873 TI - Increasing public awareness of the risk of cardiovascular disease using 'health activists' in a community health project in Israel: a feasibility study. AB - An innovative approach to health education in the field of cardiovascular risk factor control was implemented in an urban community in southern Israel. The objective of the project was to determine the efficiency of utilising lay health activists (HAs) to convey the health message to the community. After undergoing a selection process, 22 HAs completed the course of instruction which included: 24 hours of lectures on health topics given by medical experts; 25 hours of training in communication skills, group supervision and assistance in coping with problems encountered during their field work in the community. In the execution of their field work, the HAs paid home visits to members of the community in order that a) two questionnaires could be completed: one dealing with attitude to and knowledge of CVD risk factors and the other, with health habits; b) according to the outcome of the interview, advice concerning desirable changes in life-style could be offered, and c) a follow-up visit could be made in order to reinforce the health message and to evaluate any changes in knowledge, attitudes and behaviour. During the 18 weeks of the project, 612 homes were visited by the HAs. Evaluation of the project is based on an assessment of the changes in knowledge, attitudes and behaviour of the HAs themselves. Results of this study suggest that improving the efficiency of health promotion by utilising the services of lay health activists is a viable proposition. Finally, the applicability of the programme is discussed. PMID- 2258874 TI - Evaluation of two educative models in a primary care hypertension programme. AB - This study was planned in the context of a regional high blood pressure programme, to compare the efficacy of two educative methods. The group of 722 hypertensive patients (58.8% women), mean age 61 years, was randomly selected from 19 primary care centres. Initial assessment was based on a patient interview including 22 questions on high blood pressure, its consequences and treatment. Patients agreeing to participate in an active education team programme were distributed into three groups: individual education, team education and a control group. Those who declined to participate formed two groups: individual education and controls. Team education consisted of two audiovisual sessions attended by groups of 8-12 patients and conducted by treating physicians and nurses. Individual education included comments related to the 22 questions. Follow-up assessment was made after two months. An increase in the level of hypertension control was observed only in the accepting group, in which educative action was followed by increased knowledge. Results were similarly favourable for both the individual and team education groups and suggested the need to consider educational factors together with those influencing patient attitude towards an active educational programme. PMID- 2258875 TI - Preventive cardiology in general practice: computer-assisted hypertension care. AB - Research investigations of general practice on the prevention of cardiovascular disease indicate that preventive detection and intervention programmes can be effective. Long-term results on hypertension control are better when systematic follow-up accompanies surveillance of the hypertensive population. Based on research and international experience, we developed the Nijmegen Hypertension Monitoring System, a computer-assisted system consisting of monthly feedback of treatment results and regular meetings of the participating general practitioners. We describe an experiment in seven study practices and eight practices continuing with usual care, to study the effectiveness and feasibility of the system. This Monitoring System could also be adapted for other chronic diseases. PMID- 2258876 TI - Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (1). The first three months. AB - Thirty-five patients with mild to moderate hypertension were randomised into a three months' dietary advised and a three months' control group. The diet was of a composition currently considered to be appropriate, and was monitored by a dietitian. Statistically significant decreases in diastolic blood pressure, mean arterial pressure, sodium excretion, and low density lipoprotein (LDL) cholesterol occurred in the intervention group, although differences in change between the intervention and the control group were, except for LDL-cholesterol, not statistically significant. Thus, it did not become clear whether and to what extent change in diet was responsible for the lowering of the blood pressure in the intervention group. PMID- 2258877 TI - Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (2). Beyond three months. AB - In a general primary care practice the feasibility and the effects of dietary counselling in mild and moderate hypertension were studied for a period of 18 months. Significant decreases in blood pressure and sodium excretion compared to baseline occurred, while serum lipids showed transient improvement. Of the original 35 participants, 28 finished the study. PMID- 2258878 TI - Resource savings from non-pharmacological control of hypertension. AB - Treatment of acute cardiovascular illness is expensive, and a preventative approach may be cheaper. Since pharmacological costs account for a large proportion of costs in prevention programmes, a non-pharmacological approach such as that used by us in Ashkelon on mild hypertensives, relying on stress management, weight management and exercise aimed at reducing risk factors, might prove to be more cost-effective. After six months on a 1,000 calorie/day diet, 69 obese subjects (initial body mass index greater than 28 kg/m2) had reduced their weight by an average of 7.3 kg (P less than 0.005). This weight reduction contributed to a significant decrease in systolic blood pressure (SBP) from 157.3 to 137.6 mmHg (P less than 0.005) and diastolic blood pressure (DBP) from 101.1 to 85.2 mmHg (P less than 0.005), which was sustained at two-year follow-up. Pharmacological treatment could be stopped in about one-quarter of these cases. In non-obese mild-hypertensives, deep muscle relaxation and biofeedback techniques were prescribed. Significant decreases in SBP (153.1 to 138.3 mmHg, P less than 0.005) and DBP (101.2 to 90.1 mmHg, P less than 0.005) were achieved at six months. In nine out of 19 cases pharmacological treatment was stopped after six to eight months. Smoking cessation was achieved by individual instruction together with stress management techniques, physical exercise and a nicotine based chewing gum. After six months 18 out of 30 heavy smokers had stopped smoking, and the remaining 12 had reduced their cigarette consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258879 TI - Hypertension as a cause of end-stage renal failure in South Africa. AB - We reviewed the data of 3,632 patients with end-stage renal failure entered into the South African Dialysis and Transplantation Registry over a six-year period. The male to female ratio was 1.4:1. Of these patients, 48.8% were white, 26.2% black, 17.6% coloured and 7.4% Asian. Essential hypertension was the cause of end stage renal failure in 15.9% of patients. Malignant hypertension was the diagnosis in 57% of the essential hypertensives. Hypertension was responsible for 34.6% of end-stage renal failure in blacks, 20.9% in coloureds, 4.3% in whites and 13.8% in Asians. In the age group 30-39 years, 37.4% of patients with malignant hypertension commenced dialysis, while 28.4% and 28.8% of benign hypertensives commenced dialysis in the 30-39 and 40-49 age groups, respectively. The survival at 36 and 72 months was the same whether hypertension was the cause of end-stage renal failure or not, and whether the hypertension was malignant or benign. Cardiac causes were responsible for most of the deaths. The percentage of deaths from cardiac causes was similar in patients with renal failure from essential hypertension and other causes (33.2% and 29.3% respectively). Hypertension is the commonest cause of end-stage renal failure in black South Africans and the most common preventable cause of end-stage kidney disease in the country. PMID- 2258880 TI - Circadian variation of haemodynamics in patients with essential hypertension. AB - A Holter BP monitor and a noninvasive, continuous cardiac output (CO) monitor were concurrently attached to 25 middle-aged hospitalized patients with essential hypertension (EH). Blood pressure, heart rate (HR) and CO were measured every 10 minutes over 24 hours. Circadian variation of mean BP was studied. Comparison of values to the 6:00 value revealed a significant increase in mean BP during the active hours of the day. Mean BP during the sleeping hours, on the other hand, was significantly lower than during the awake hours. The circadian variations of CO and HR demonstrated similar fluctuations to those of mean BP. The circadian variation of the CO change ratio based on the 6:00 CO value was similar to that of mean BP. Circadian variation of total peripheral resistance (TPR) change ratio based on the 6:00 value demonstrated an inverse relation to the mean BP. It is suggested that the relation between TPR and CO in the circadian variation might be described as high output-low resistance. PMID- 2258881 TI - Comparison of circadian blood pressure variations in hypertensive patients with renal artery stenosis and essential hypertension. AB - Ambulatory blood pressure measurements in 20 hypertensive patients with uni- or bilateral renal artery stenosis were compared with those in 20 essential hypertensive patients. Analysis of the 24 hour blood pressure curve of the renal artery stenosis group shows a tendency to equalization of blood pressure throughout the day. The nocturnal decrease of systolic or diastolic blood pressure was not significantly different between the two groups (9.2 vs. 15.3 mmHg). The blunted curve seems to be related more to the severity of hypertension than to its aetiology, but further studies are required to elucidate this point. PMID- 2258882 TI - Twenty-four hour ambulatory blood pressure in therapeutically resistant hypertensive patients. AB - Circadian blood pressure and heart rate rhythms were determined in essential and renal hypertensive patients who failed to respond to drug therapy. Indirect ambulatory blood pressure and heart rate recordings were measured in 31 subjects for 24 hours. Essential hypertensive patients exhibit 'white coat hypertension', are normotensive outside the clinic and have a higher awake than sleep blood pressure. Blood pressure and heart rate of renal hypertensive patients do not increase in the presence of a physician and there is no difference between awake and sleep values. In contrast to patients with essential hypertension, the circadian fluctuations of blood pressure were depressed in renal hypertensive patients. We conclude that essential hypertensive patients who appear clinically uncontrolled are in fact well controlled in their domestic environment, whereas renal hypertensive patients are consistently uncontrolled. Ambulatory monitoring may help in differentiating the various types of patient and in the evaluation of antihypertensive therapy. PMID- 2258883 TI - Effect of removal of phaeochromocytoma on diurnal variability of blood pressure, heart rhythm and excretion of catecholamines. AB - Ambulatory 24 hour blood pressure and ECG monitoring with simultaneous estimation of the urinary excretion of noradrenaline and adrenaline were performed in seven patients with phaeochromocytoma, before and after removal of the tumour. Mean blood pressure during eight 3-hour periods, mean heart rate, and noradrenaline and adrenaline excretion during four 6-hour periods were estimated. Mean blood pressure before surgery did not show any significant circadian changes. After surgery both systolic and diastolic blood pressures were significantly lower at night than in the daytime periods. In contrast, mean heart rate before surgery was significantly lower at night than in the morning, and this relationship was greater after surgery. Ventricular arrhythmias during 24 hour monitoring were noted in three patients before and in six after surgery. These findings suggest that profound disturbances of autonomic blood pressure regulation improve after removal of phaeochromocytoma, and that ventricular arrhythmias, except for paroxysmal symptoms, tend to be less frequent before than after surgery. PMID- 2258884 TI - Differences in ambulatory blood pressure between men and women with mild hypertension. AB - Non-invasive ambulatory blood pressure monitoring was performed in a consecutive series of 87 subjects with recently detected mild uncomplicated hypertension. Obese subjects, diabetics and those with secondary hypertension were excluded. Ambulatory pressures were recorded on a day of usual activity. Average ambulatory systolic and diastolic pressures were significantly lower than referral pressures determined in clinics or screening sites and initial pressures taken by the monitors. Whereas men (57) and women (30) had similar referral and initial pressures, average ambulatory systolic pressure was significantly higher in men; diastolic pressure was not different. Men also had a significantly higher fraction of ambulatory systolic pressures greater than 140 mmHg compared to women. Fifty-six percent of the men and 80% of the women had average ambulatory systolic pressures less than 140 mmHg and diastolic pressures less than 90 mmHg; the difference between the sexes was significant (chi 2 = 6.99, P less than 0.01). Thus, in mild hypertension, women have lower average systolic pressure than men during ordinary daily activity. These results may account for lower long term cardiovascular morbidity in hypertensive women compared with men. PMID- 2258885 TI - Differences in blood pressure profile between young and elderly hypertensive patients. AB - We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/ 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258886 TI - Acute and long-term treatment of hypertension with nifedipine in the elderly. AB - The acute hypotensive effect of nifedipine was evaluated, and the possibility of its long-term use in hypertensives over 60 years of age was studied. Sublingual nifedipine in a dose of 20 mg was given to 28 patients, mean age 73.1 yrs, and blood pressure, heart rate, and plasma drug concentration were monitored at 15 min, and every 30 min thereafter for 3 hrs. Systolic and diastolic blood pressure decreased at 15 min by 22.1 and 7.0 mmHg, respectively, reaching a maximal decrease two hours after drug administration. The decrease in blood pressure level did not correlate with nifedipine plasma concentration, but only with the initial systolic blood pressure. Long-term treatment with nifedipine was initiated in 60 patients, with 45 patients completing the study. Mean age was 66.2 years. An initial dose of 30 mg daily had to be increased to 60-80 mg in one third of the patients. Monotherapy was not satisfactory in some patients. Blood pressure gradually decreased from 173/99 to 148/85 mmHg at three months, and to 141/84 mmHg at six months. Drug tolerance was fairly good. Nifedipine was withdrawn due to a considerable increase in heart rate in three patients and skin allergy in one. The most frequent adverse symptoms were: rash, headache, and leg oedema. Laboratory tests revealed no changes in urea and creatinine, and an increase in fasting glycaemia. Lipid parameters did not change significantly. These data proved that a single dose of 20 mg of nifedipine produced therapeutic plasma concentration of the drug and good hypotensive effect, positively correlating with initial systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258887 TI - The differential efficacy of antihypertensive agents in the elderly. AB - A number of controlled trials have shown that antihypertensive therapy is beneficial to the elderly (greater than or equal to 60 years of age). Even so, there may be deleterious age-related effects associated with such therapy. Because of physiological and pathophysiological problems peculiar to the elderly (many of which remain to be defined precisely), both benefits and untoward effects of antihypertensive drugs differ, sometimes within classes of agents themselves. None of the traditional agents is ideal for the management of hypertension in the elderly. Differential efficacy and tolerability of various antihypertensive agents has often been claimed but none of these claims appears established beyond dispute. Increasing evidence, however, suggests that the serotonin antagonist ketanserin may be more effective and better tolerated in elderly hypertensives. If the elderly are to derive maximum benefit from antihypertensive therapy, the question of age-related differential effects of agents used needs to be addressed in carefully designed studies to determine the nature and magnitude of such effects, where they exist and what clinical implications they may have. PMID- 2258888 TI - Hypertension and vascular disease in India and migrant Indian populations in the world. AB - The association of hypertension, diabetes mellitus and abnormal lipoprotein patterns suggests that this combination has a lethal effect with regard to vascular disease. It is therefore necessary to do something about the known lifestyle factors such as cigarette smoking, obesity and possibly a low fibre diet. The high incidence of ischaemic heart disease among emigrant Indians in South Africa and Trinidad, and the low incidence in blacks of South Africa and the West Indies, suggests that there may be different thresholds for susceptibility to disease in various ethnic groups, beyond which the risk factors begin to operate. PMID- 2258889 TI - Levels and correlates of blood pressure in recent and earlier Ethiopian immigrants to Israel. AB - Blood pressure (BP) and anthropometric data were collected on 483 recent immigrants from Ethiopia to Israel, and on 171 adults and 100 adolescent boarding school students who had immigrated two to three years earlier. Comparison of samples within the Ethiopian groups, and between new and early Ethiopian immigrants with Israel and resident Israelis revealed the following: Systolic and diastolic BP were considerably lower in recent immigrants of both sexes than among counterparts residing in Israel for two to three years. The latter group significantly approached, but did not reach, the BP levels of veteran Israelis. A similar comparison of 100 immigrant Ethiopian boarding school children with an Israeli high school population revealed apparently larger differences among the boys than the girls, whose BP was 'adapted' to a greater degree. Differences in relative weight paralleled those identified for BP, with the Quetelet index (QI) progressively higher when comparing new immigrants with earlier ones, and with persons who have lived in Israel for a longer period. Whether the weight differences provide a complete explanation for BP changes cannot be definitely stated, pending prospective data on weight and BP changes. Correlations of BP with anthropometric parameters and pulse rate indicated that weight rather than QI was the stronger correlate of BP in adults, whereas weight and height, but not QI, correlated with BP in adolescent boys. QI correlated with BP in adolescent, apparently sexually mature girls, but not in boys. PMID- 2258890 TI - Obesity and hypertension: epidemiological aspects of the relationship. AB - A large proportion of hypertensive men and women in Europe and North America are overweight. In obesity, the expanded blood volume increases cardiopulmonary volume, cardiac filling, left ventricular preload, stroke volume and, thereby, left ventricular work. Given enough exposure time, it is probable that all obese persons in the Western hemisphere would become hypertensive unless they succumb to competing causes of death. A postulated causal role of obesity in hypertension is based on epidemiological observations. In prospective studies weight gainers in adolescence are more often hypertensive than weight stable individuals. In the lower socio-economic strata of industrialized countries there is a higher prevalence of obesity and hypertension. Persons with high body weight show the greatest rise of BP with age. More relevant demonstration of a causal relationship is weight reduction in hypertensive patients. The evidence from a variety of sources, a) risk factor reduction and enhanced BP reduction in the Hypertension Detection and Follow-up Program patients on antihypertensive medication who experienced modest weight loss, b) clinical observations of formerly obese hypertensives who can forego BP lowering drugs, and c) the reversibility of haemodynamic change found in many overweight hypertensive patients after losing 10 kg, strongly suggests that the impact of obesity on hypertension is considerable. PMID- 2258891 TI - Age, platelet serotonin kinetics and 5HT2-receptor blockade in essential hypertension. AB - Serotonin (5HT) released from activated platelets causes platelet aggregation and vasoconstriction which are both exaggerated in older age and contribute to the development of thromboembolic complications. Platelet 5HT kinetics and reactivity were investigated in 45 patients with essential hypertension and 45 healthy control subjects matched for age, sex and smoking status. An age-dependent attenuation of total 5HT turnover and platelet 5HT release was revealed in control subjects but not in patients with essential hypertension. In the latter, especially in men, platelet 5HT uptake decreased with age and high blood pressure, leading to elevated 5HT plasma concentration. In parallel, platelet reactivity was increased with advancing age as shown by a greater 5HT induced aggregation and higher beta-thromboglobulin plasma concentration. Antihypertensive treatment with ketanserin resulted in inhibition of 5HT-induced shape change reaction and aggregation as well as a decrease in platelet 5HT release. Age contributes to altered platelet 5HT kinetics and 5HT2-receptor reactivity thereby elevating thromboembolic risk. 5HT2-receptor blockade with ketanserin interferes with these events by inhibition of platelet 5HT release and by a greater antiaggregatory and antihypertensive action in older age. PMID- 2258892 TI - Do angiotensin-converting enzyme inhibitors work in black hypertensives? A review. PMID- 2258893 TI - Long-term effects of pindolol and a thiazide diuretic on plasma lipids and blood pressure in patients with essential hypertension. AB - A retrospective analysis was made from the charts of 53 patients with mild to moderate essential hypertension to determine the effects of pindolol (PIN) monotherapy, hydrochlorothiazide (HCTZ) added to PIN monotherapy, and PIN added to HCTZ monotherapy on serum lipids and blood pressure. PIN monotherapy (Group I, n = 24) resulted in a significant decrease in systolic and diastolic pressure of 12.0 and 9.0 mmHg at three months and 14.0 and 11.0 mmHg at 12 months, respectively. Serum triglycerides, total cholesterol, low density lipoprotein and high density lipoprotein cholesterol fractions remained unchanged. The addition of 25 mg of HCTZ to PIN (Group II, n = 7) resulted in a significant decrease in both systolic and diastolic pressure of 21.0 and 11.0 mmHg at three months and 24.0 and 11.0 mmHg at 12 months, respectively. No change in serum lipids was noted. Adding PIN to 25 mg HCTZ (Group III, n = 22) resulted in a significant decrease in systolic and diastolic pressure of 18.0 and 9.0 mmHg at three months and 20.0 and 10.0 mmHg at 12 months, respectively, with no change in serum lipids noted. These data indicate that long-term administration of PIN, a drug possessing intrinsic sympathomimetic activity, alone or added to a low dose of a thiazide diuretic does not adversely affect serum lipids. The addition of a small dose of a thiazide diuretic to PIN has no long-term effect on plasma lipids. PMID- 2258894 TI - Influence of co-dergocrine mesilate/nifedipine compared to mefruside/nifedipine on circadian blood pressure in patients with essential hypertension. AB - This randomised, parallel group study was designed to compare the efficacy of nifedipine (40 mg once daily) combined with either the dopamine agonist, co dergocrine mesilate (4 mg once daily) or the diuretic mefruside (25 mg once daily) in 40 patients with essential arterial hypertension and a diastolic blood pressure greater than 105 mmHg. Circadian blood pressure and heart rate were measured over 24 h every 15 min from 6 a.m. to 6 p.m. and every 30 min from 6 p.m. to 6 a.m. with an automatic, portable instrument (ICR 5300, Squibb) before and after a three-week treatment period. At the end of the three-week treatment period the mean value of all 24 h blood pressure measurements reflected highly significant decreases (2P less than 0.001), from 148/92 +/- 16/12 before treatment to 131/83 +/- 12/12 mmHg after treatment in the co-dergocrine mesilate/nifedipine group and from 145/92 +/- 16/10 before treatment to 129/84 +/ 10/6 mmHg after treatment in the mefruside/nifedipine group. Blood pressure reduction was still significant in both groups during the early morning hours at the end of the dosage interval. The efficacies of nifedipine combined with co dergocrine mesilate or mefruside were comparable but side-effects were rated as more severe in the mefruside group. Therefore, the combination co-dergocrine mesilate/nifedipine may be preferable to the combination mefruside/nifedipine. PMID- 2258895 TI - Verapamil versus nifedipine in slow-release preparations for the treatment of mild to moderate hypertension. AB - A crossover study with 24-hour ambulatory blood pressure monitoring was conducted on 30 hypertensive patients, using slow-release preparations of verapamil and nifedipine. Both drugs proved effective hypotensive agents. Nifedipine was slightly, but not significantly, more potent. Fewer side effects were observed with verapamil, but both drugs were well tolerated. PMID- 2258896 TI - Evidence for nitroxyl in the catalase-mediated bioactivation of the alcohol deterrent agent cyanamide. PMID- 2258897 TI - A novel synthesis of xanthines: support for a new binding mode for xanthines with respect to adenosine at adenosine receptors. PMID- 2258898 TI - Chiral modifications of dolastatin 10: the potent cytostatic peptide (19aR) isodolastatin 10. PMID- 2258899 TI - Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation. AB - Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site. PMID- 2258900 TI - Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia. AB - 5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia. PMID- 2258901 TI - Synthesis and estrogen receptor binding of novel 11 beta-substituted estra 1,3,5(10)-triene-3,17 beta-diols. AB - As part of our program to develop estrogenic radioligands for use in nuclear medicine, a study was undertaken to investigate the effect of substituents on the receptor affinity of putative radiochemicals. In the study a synthetic strategy directed toward the introduction of an 11 beta-(fluoroethyl) substituent was devised. The target compound 9 was prepared via a five-step procedure starting from 11 beta-vinylestrone 3-acetate (4) in an overall 43% yield. The stereochemistry of the 11 beta-vinyl moiety was established by X-ray crystallography. The final product and several analogues, 11 beta-ethyl-, -vinyl , and (hydroxyethyl)estradiols (11, 5, and 12), were evaluated for their estrogen receptor binding affinity. The results indicate that the target compound and several 11 beta-substituted analogues possess relative binding affinities greater than of estradiol and its 16 alpha-fluorinated derivatives. The manner in which the target compound 9 was prepared is amenable to use with 18F incorporation. PMID- 2258902 TI - Synthesis and cytotoxicity studies of 8-amino-6-methyl-2-beta-D-ribofuranosyl 1,2,3,5,6,7-hexaazaacenaphthyle ne (7-aza-TCN) and the corresponding 2'-deoxy- and arabinonucleoside analogues. AB - The tricyclic nucleoside 8-amino-6-N-methyl-2-beta-D-ribofuranosyl-1,2,3,5,6, 7 hexaazaacenaphthylene was synthesized from 8-amino-6-N-methyl-4-(methylthio)-2 beta-D-ribofuranosyl-1,2,3,5,6, 7-hexaazaacenaphthylene. The 2'-deoxy analogue of 5, 8-amino-6-N-methyl-2-(2-deoxy-beta-D-ribofuranosyl)-1,2,3,5,6, 7 hexaazaacenaphthylene (11), and the arabino analogue of (5), 8-amino-6-N-methyl-2 beta-D-arabinofuranosyl-1,2,3,5,6, 7-hexaazaacenaphthylene (14) were synthesized from 5. Nucleosides 2,3,4,5,11, and 14 were evaluated for potential anticancer activity by measuring their ability to inhibit the growth of L1210 and H. Ep. 2 tumor cells in vitro. PMID- 2258903 TI - Synthesis and biochemical evaluation of tritium-labeled 1-methyl-N-(8-methyl-8 azabicyclo[3.2.1]oct-3-yl)-1H-indazole-3-carboxa mide, a useful radioligand for 5HT3 receptors. AB - The advent of potent, highly selective 5HT3 receptor antagonists has stimulated considerable interest in 5HT3 receptor mediated physiology and pharmacology. To permit detailed biochemical studies regarding interaction of the indazole class of serotonin (5HT) antagonists with 5HT3 receptors in multiple tissues, we synthesized 1-methyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazole- 3 carboxamide (LY278584, compound 9) in high specific activity, tritium-labeled form. This radioligand was selected as a synthetic target because of its potency as a 5HT3-receptor antagonist, its selectivity for this receptor viz a viz other 5HT-receptor subtypes, and the ability to readily incorporate three tritia via the indazole N-CH3 substituent. Alkylation of N-(8-methyl-8-azabicyclo[3.2.1]oct 3-yl)-1H-indazole-3-carboxamide (8) with sodium hydride and tritium-labeled iodomethane, followed by HPLC purification, resulted in [3H]-9 with a radiochemical purity of 99% and a specific activity of 80.5 Ci/mmol. This radioligand bound with high affinity to a single class of saturable recognition sites in membranes isolated from cerebral cortex of rat brain. The Kd was 0.69 nM and the Bmax was 16.9 fmol/mg of protein. The specific binding was excellent, and accounted for 83-93% of total binding at concentrations of 2 nM or less. The potencies of known 5HT3-receptor antagonists as inhibitors of [3H]-9 binding correlated well with their pharmacological receptor affinities as antagonists of 5HT-induced decreases in heart rate and contraction of guinea pig ileum, suggesting the central recognition site for this radioligand may be extremely similar to or identical with peripheral 5HT3 receptors. PMID- 2258904 TI - Resolved pyrrolidine, piperidine, and perhydroazepine analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide. AB - A series of conformationally restricted analogues of the partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 1) was synthesized. Three of the racemic derivatives were resolved into the enantiomers. The compounds were investigated for muscarinic and antimuscarinic activity in the isolated guinea pig ileum. They were found to be fairly potent muscarinic antagonists or weak partial agonists. The new compounds were either equally or less potent than 1 in inhibiting (-)-[3H]-N-methylscopolamine binding in homogenates of the rat cerebral cortex. Thus, structural modifications to 1 in which the amide moiety and the methyl group in the butynyl chain have been joined to form a six- or seven-membered ring preserve affinity but abolish efficacy. The R enantiomers were found to have 14-79 times higher affinity to ileal muscarinic receptors than the respective antipodes. The enantiomeric affinity ratios were nearly identical in both preparations studied. As suggested by molecular mechanics calculations, the difference in affinity between the five-membered and the six- and seven-membered ring analogues may be rationalized in conformational terms. PMID- 2258905 TI - Chemical and biochemical studies of 2-propynylpyrrolidine derivatives. Restricted rotation analogues of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5). AB - A series of optically pure 2-[substituted-3-aminopropynyl]pyrrolidine derivatives, which are restricted-rotation analogues of the muscarinic agent N methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5, compound 1), have been prepared from d- and l-proline. The compounds when tested in a series of in vitro muscarinic assays [[3H]CD (cortex), [3H]QNB (cortex), [3H]PZ (cortex), [3H]QNB (heart), [3H]QNB + GppNHp (heart)] were found to have weaker muscarinic properties than compound 1. The decrease in affinity was attributed to the increased size of the molecule resulting from the addition of a methylene group to form the pyrrolidine ring. The use of optically active compounds provided a more detailed examination of the complex pharmacological effects of the flexible muscarinic agent 1. The R enantiomers in the acetamide derivatives 12b, 12d, and 12f had a 5-10-fold greater affinity for the muscarinic receptor than the corresponding S enantiomers. A 5-fold difference or less found in the (R)- and (S)-carbamate derivatives 9, 15, and 16 suggested close overlap of the two enantiomers in the receptor binding domain. The affinity differences found in the enantiomeric acetamido derivatives when compared to those of the carbamate analogues may be the result of limited rotation of the acetamido group. PMID- 2258906 TI - Structure-activity relationship of antiestrogens. Studies on 2,3-diaryl-1 benzopyrans. AB - A series of 2,3-diaryl-1-benzopyran analogues substituted at position 4 of 2 phenyl with a hydroxy or pyrrolidinoethoxy residue were synthesized as models for (E)-triarylpropenones constrained in the s-trans conformation. The prototypes, belonging to five chemical series, were evaluated for their estrogen receptor affinity and for estrogen agonist-antagonist activities. The 4H-1-benzopyran-4 one, the 2,3-dihydro-4H-1-benzopyran-4-one, the 4H-1-benzopyran, and the 2,3 dihydro-1-benzopyran derivatives were found to be inactive or only marginally activate as receptor ligands or estrogen agonists-antagonists. In the 2H-1 benzopyran category the parent phenol was also inactive whereas the basic ethers 16 and 26 were modest receptor ligands while being quite active as antiestrogens. In a comparative study the benzopyran 16 was found to be more effective antiestrogen than tamoxifen while being as effective as LY-117018. The benzopyrans have thus emerged as a new class of potent antiestrogens. PMID- 2258907 TI - Structure-activity relationship of antiestrogens. Effect of the side chain and its position on the activity of 2,3-diaryl-2H-1-benzopyrans. AB - A series of 2,3-diaryl-2H-1-benzopyrans carrying a tertiary aminoethoxy chain at the ortho, meta, or para position of 2-phenyl or an alkyl at position 4 of the pyran ring were synthesized and evaluated for their affinity for estrogen receptor (ER) and for microsomal antiestrogen specific binding site and for their uterotrophic-antiuterotrophic activities in rodents. The analogues bearing the side chain at the para position of 2-phenyl were found to be active while those substituted at the meta and ortho positions were inactive as ER ligands as well as estrogen agonists-antagonists. Among para-substituted ethers, the 2 piperidinoethoxy analogue 5 was found to be a more effective antiestrogen than the corresponding pyrrolidino, dimethylamino, and related analogues. Incorporation of a methyl or an ethyl at C4 in the pyran nucleus was found to increase receptor affinity of the prototypes. The ethyl was also found to potentiate agonist activity of the prototype while abolishing its antagonist activity. The piperidino analogue 5 was found to be a better antiestrogen than tamoxifen as well as LY-117018 in rats as well as mice. The prototypes were also found to have high affinity for the microsomal antiestrogen specific binding sites. The benzopyrans have thus emerged as a new group of potent antiestrogens. PMID- 2258908 TI - Structure-activity relationship of antiestrogens. Phenolic analogues of 2,3 diaryl-2H-1-benzopyrans. AB - Phenolic analogues of 2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (1), a novel antiestrogen, were synthesized and evaluated for their structure activity relationship. Incorporation of OH at position 7 was found to improve receptor affinity of the benzopyran while having no effect on its action as an antagonist. Similar substitution of 2-phenyl as well potentiated receptor affinity as well as antagonist activity of the prototype. The monophenol 19 and the diphenol 25 were thus found to be good receptor ligands, devoid of estrogen agonist activity and associated with marked antiestrogenic activity of comparable order. Both caused nearly complete inhibition of the estradiol stimulated uterine growth in rats as well as mice and were thus found to be better antiestrogens than tamoxifen, trioxifen, and LY-117018. A binding-site model for estrogen receptor rationalizing the structure-activity relationship of benzopyrans in relation to that of the triarylethylene and the triarylpropenone antiestrogens has been discussed. PMID- 2258909 TI - 12th C. L. Oakley lecture. Pathogenesis of Clostridium difficile infection of the gut. AB - On the basis of the above findings it is possible to propose a sequence of events following exposure to C. difficile. Exposure of neonates to C. difficile leads to transient colonisation which is almost invariably asymptomatic; the reasons why colonisation is asymptomatic are not known. Exposure of antibiotic-treated adults to C. difficile does not invariably lead to colonisation; however, in those instances where colonisation occurs, it may be transient and asymptomatic or transient and symptomatic. The transient nature of the colonisation could be because the infecting strain is poorly virulent, or because the degree of compromise of the intestinal flora is insufficient to permit establishment and full expression of virulence. It is likely that it is easier to fully compromise the intestinal flora of the elderly so that they more readily become fully susceptible to colonisation by C. difficile. In a fully susceptible host and with a highly virulent strain, the following sequence of events could occur. The organism may associate with the intestinal mucosa possible via fimbriae, and form a microcolony of capsulate cells protected by a glycocalyx. The toxins, or other factors, produced may facilitate the interaction with mucosa and toxin A will result in increased vascular and mucosal permeability resulting in intra-luminal accumulation of serum-albumin-rich fluid. Although C. difficile does not appear to be capable of using serum albumin nutritionally, it may utilise other serum proteins, and the serum proteins in general may compete with host proteases and help prevent degradation of the toxins produced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258910 TI - Production of mouse monoclonal antibodies to Pasteurella multocida type A and the immunological properties of a protective anti-lipopolysaccharide antibody. AB - Eight monoclonal antibodies (MAbs) were produced from mice immunised with whole cells of heat-killed Pasteurella multocida type A which had been cultured under iron-restricted conditions. The MAbs were selected by an enzyme-linked immunosorbent assay (ELISA) in which the antigen consisted of whole bacteria of the immunising strain. Their reactivity was investigated further by immunoblotting, indirect haemagglutination, a complement-mediated bactericidal assay and passive protection of mice. One of the eight MAbs was shown by immunoblotting to react with lipopolysaccharide (LPS), was bactericidal, and completely protected mice against homologous challenge with 10 LD50 of live bacteria. This MAb was selected for further study. Its reaction with LPS of 17 type-A strains and of single strains of types B, D and E was investigated by immunoblotting. Strains that reacted with the anti-LPS MAb in immunoblots were susceptible to its bactericidal activity and gave high ELISA absorbances. Those that did not react were not susceptible to its bactericidal activity and gave low ELISA readings. The relation between bactericidal activity and ELISA absorbance was highly significant (p less than 0.001). Five of the strongly reacting heterologous strains and one non-reacting strain were selected as challenge organisms in a passive protection experiment: only the mice receiving the reacting strains were protected. PMID- 2258911 TI - Comparison of identification methods for oral asaccharolytic Eubacterium species. AB - Thirty one strains of oral, asaccharolytic Eubacterium spp. and the type strains of E. brachy, E. nodatum and E. timidum were subjected to three identification techniques--protein-profile analysis, determination of metabolic end-products, and the API ATB32A identification kit. Five clusters were obtained from numerical analysis of protein profiles and excellent correlations were seen with the other two methods. Protein profiles alone allowed unequivocal identification. PMID- 2258912 TI - Purification and characterisation of an extracellular serine proteinase from Aspergillus fumigatus and its detection in tissue. AB - A serine proteinase (Alp) from the culture supernate of a clinical isolate of Aspergillus fumigatus was purified to virtual homogeneity at a yield of 41%. The procedure involved affinity chromatography on agarose-epsilon-amino-caproyl-D tryptophan methyl ester. Alp had an estimated mol. wt of 32 Kda and the pI was determined at pH 7.9. The enzyme was fully inhibited by phenylmethyl sulphonyl fluoride, chymostatin and alpha-1-proteinase inhibitor, and it was largely inhibited by alpha-1-anti-chymotrypsin. Partial inhibition was observed with tosyl-phenylalanine chloromethyl ketone, but tosyl-lysine chloromethyl ketone was ineffective. Thus, Alp may be identical with the major chymotryptic activity of A. fumigatus, which has already been described. The N-terminal sequence of 25 amino acids revealed an 88% homology of Alp with the subtilisin-related proteinase of A. oryzae. Alp acted on casein over a broad range from pH 5.5 to 11.5 and also acts to a lesser extent on haemoglobin and serum albumin. The enzyme degraded elastin and a synthetic elastase substrate; hence, it may be identical with the previously described elastinolytic activity of the fungus. At pH 7.3 and a concentration of 1 microgram/ml, Alp was not toxic for Vero cells, but it efficiently detached such cells from a plastic surface. Specific antibodies against Alp were detected by enzyme immunoassay in the sera of patients and Alp-antigen was demonstrated by immunofluorescence in mycotic human lung. In addition, a second proteinase (Exalp) with extremely alkaline activity, and an aspartic proteinase of A. fumigatus are described. PMID- 2258913 TI - 3-deoxy-D-manno-2-octulosonic acid in the lipopolysaccharide of various strains of Pseudomonas cepacia. AB - Six clinical isolates of Pseudomonas cepacia (representing the five serotypes of the organism) were examined for the presence of 3-deoxy-D-manno-2-octulosonic acid (KDO) in their lipopolysaccharide (LPS). Purified LPS was examined for the presence of KDO by the thiobarbituric acid (TBA) assay and by gas chromatography. All strains possessed KDO. One strain possessed KDO that was detectable by the TBA assay after mild acid hydrolysis with 0.04 M H2SO4 at 100 degrees C for 20 min. The other strains also possessed KDO but it was only demonstrable by the TBA assay after strong acid hydrolysis (4 M HCl for 60 min at 100 degrees C). All six purified LPS preparations were shown to possess KDO by two separate gas chromatography procedures. LPS isolated from the six strains of P. cepacia was toxic for mice. PMID- 2258914 TI - Detection of Haemophilus influenzae in cerebrospinal fluids by polymerase chain reaction DNA amplification. AB - Two primer sets were chosen for the detection of Haemophilus influenzae in cerebrospinal fluid by polymerase chain reaction (PCR) DNA amplification. One primer set was selected from sequences encoding a capsulation-associated protein and reacted with target DNA from all 15 capsulate H. influenzae strains (all serotypes) examined. The other primer set was selected from the DNA sequence of a gene encoding for outer-membrane protein P6 and reacted with the 15 capsulate and 10 non-capsulate strains of H. influenzae tested. This primer set also reacted with the closely related species H. haemolyticus and H. aegyptius, and with two of nine H. parainfluenzae strains. In reconstruction experiments, PCR DNA amplification was able to detect as few as five H. influenzae cells when 40 cycles of amplification were used. Two hundred cerebrospinal fluid (CSF) samples collected consecutively from patients suffering from meningitis were investigated by PCR; 40 were culture-positive for H. influenzae and 39 of these were also clearly positive in the PCR test with both primer sets. Contamination occurred to some extent with 40 cycles of amplification but was completely eliminated when the number of cycles was reduced to 35. We conclude that the two primer sets are appropriate for the detection of H. influenzae by PCR, each having its own specificity. When these two primer sets are used, PCR is a technique of equivalent sensitivity to culture for the detection of H. influenzae in CSF. PMID- 2258915 TI - Soluble and cell-associated haemagglutinins of Helicobacter (Campylobacter) pylori. AB - Some plate-grown strains of Helicobacter (Campylobacter) pylori that were harvested into phosphate-buffered saline and left for 1 h released soluble haemagglutinins. These caused high-titre agglutination of human and guinea-pig erythrocytes, whereas chicken, sheep and bovine erythrocytes were agglutinated at various titres. Six of 10 strains which had been subcultured repeatedly did not possess soluble haemagglutinins. Slide agglutination of bacterial suspensions demarcated the strains into two groups; Group 1 gave strong agglutination with most types of erythrocyte, Group 2 did not. By microtitration assay, all Group-1 strains but only two Group-2 strains produced a soluble haemagglutinin. Cell associated haemagglutinins were found by microtitration assay in all strains of H. pylori, but higher titres were found within Group-1 strains. The supernates of broth-grown, shaken cultures also showed the presence of soluble haemagglutinins, with higher titres for recently isolated strains. Pre-treatment of human erythrocytes with neuraminidase from Arthrobacter ureafaciens and Clostridium perfringens abolished haemagglutination by the soluble, but not by the cell associated haemagglutinin. The soluble haemagglutinin was inhibited by sialoproteins containing predominantly the N-acetylneuraminyl (2-3) galactopyranosyl [NeuAc(2-3)Gal] structure, fetuin, glycophorin and bovine N acetylneuraminyl-lactose (NeuAc-Lac). Transferrin and human NeuAc-Lac, which contain predominantly the N-acetylneuraminyl (2-6) galactopyranosyl [NeuAc(2 6)Gal] structure were not inhibitory. However, bovine submaxillary mucin (BSM) was strongly inhibitory; it contains several structures with sialic acid linked 2 6 to oligosaccharides. These results suggest that the soluble haemagglutinin recognises a NeuAc(2-3)Gal structure, but has high affinity for another, as yet undetermined, sialic acid-containing structure. PMID- 2258916 TI - Flavoprotein-fluorescence imaging for metabolic studies in multicellular spheroids by means of confocal scanning laser microscopy. PMID- 2258917 TI - Biological cryosection preparation and practical ion yield evaluation for ion microscopic analysis. AB - A mounting method utilizing an indium substrate is described for preparing freeze dried cryosections of biological tissue for ion microscopic analysis. Using this procedure, a qualitative comparison between cryosection, conventional chemical, and freeze-substitution specimen preparations is made with rat liver tissue. Practical ion yield variations in cryosections are found to be minimal (+/- 13% relative standard deviation) in tissue-containing areas of rat liver and small intestine. PMID- 2258918 TI - Assessment of particle retention and clearance in the intrapulmonary conducting airways of hamster lungs with the fractionator. AB - A modified version of the fractionator was used to estimate the total number of polystyrene microspheres retained in the airways of hamster lungs at two different time points after inhalation. A systematic three-stage subsampling procedure with known sampling fractions was adopted. First, each lung was cut into slices, from which primary disectors were sampled systematically with a known sampling fraction. From each primary disector, smaller sub-disectors were subsampled, and the corresponding sampling fraction was estimated by point counting. Finally, a few particles were counted at the microscopic level in the sub-disectors, and the final estimate of total particle number (which is unbiased irrespective of any tissue deformations) was easily computed as a product of the counted number times the reciprocal of the successive sampling fractions. The error variance of each estimate was assessed from the data using a new estimator. An average of 6% of the deposited particles were retained on the epithelial surface of the intrapulmonary conducting airways shortly after the inhalation, from which at least one-third was already phagocytosed by macrophages. After 24 h, an average of 87% of the particles retained shortly after the inhalation had been cleared. The proportion of particles ingested by macrophages had increased to at least 87% in three out of four animals studied. PMID- 2258919 TI - Measurement of boundaries using a digitizer tablet. AB - The perimeter is the most error prone of the primary measurements (length, perimeter and area) made when using a device such as a digitizer tablet to trace profiles on micrographs. To allow for minimization of this error an expression is developed relating the error in the perimeter to the digitizer resolution plus other errors in the entry process. The predictions of this expression are shown to be in good agreement with the results of computer simulation of the tracing process, as well as results from manual tracing using a digitizer tablet. This analysis of the digitizer entry process also provides a method by which an optimal choice of the sample spacing between digitizer coordinates can be made. PMID- 2258920 TI - Detection of single-stranded DNA in scrapie-infected brain by electron microscopy. AB - The nucleic acid content of enriched preparations of mitochondria/tubulofilamentous particles from normal and scrapie-infected hamster brains were examined by electron microscopy. After spreading on collodion-coated grids circular molecules of approximately 15.7 kb corresponding in size to mitochondrial DNA (mtDNA) were observed both in normal and scrapie-infected brains. In nucleic acid preparations from scrapie-infected brains multimeric mtDNA and single-stranded DNA strands of about 0.49 X 10(6) daltons were also visualized. These findings demonstrate the presence of a single-stranded DNA in scrapie-infected brains and are consistent with previous data based on enzyme digestion of nucleic acids isolated from scrapie-infected brains. PMID- 2258921 TI - Accuracy of DNA primase. AB - The base-pairing fidelity of DNA primase from calf thymus was studied in vitro by using a misinsertion assay based on synthetic polydeoxynucleotide templates. With poly(dT) as template, GMP misinsertions occurred with a frequency of one error per 1600 correctly incorporated nucleotides, while UMP and CMP were inserted with a frequency of 1/300 and 1/500, respectively. Accuracy with poly(dC, dT) as template was 1/200 for the misinsertion of UMP, and 1/300 for the misinsertion of CMP. Thus, DNA primase is the least accurate polynucleotide-synthesizing enzyme known. The results are discussed in terms of an obvious necessity for a priming mechanism at the beginning of DNA synthesis. PMID- 2258922 TI - Temperature-dependent switching between "wild-type" and "mutant" forms of p53 Val135. AB - The p53 gene is a suppressor of abnormal cell growth but is also subject to oncogenic activation by mutation. The mutant allele p53-Val135, has recently been discovered to be temperature-sensitive and functions as an oncogene at 37 degrees C and as a tumor suppressor at 32.5 degrees C. In order to investigate the molecular mechanism underlying the temperature sensitivity of p53-Val135 rabbit reticulocyte lysate was used to translate the p53 mRNAs in vitro at 37 degrees C and at 30 degrees C. The immunoreactivity and T antigen binding of wild-type protein p53-Ala135 were unaffected by temperature and were similar to wild-type p53 expressed in vivo. In contrast, the mutant p53-Val135 protein was markedly affected by temperature. At 37 degrees C p53-Val135 showed reduced T antigen binding and did not react with monoclonal antibodies PAb246 and PAb1620. At 30 degrees C, p53-Val135 behaved as the wild-type p53. Temperature also exerted a post-translational effect on p53-Val135 with complete conversion from wild-type to mutant phenotype within two minutes of temperature shift from 30 degrees C to 37 degrees C. There was incomplete conversion from mutant to wild-type phenotype when the temperature was shifted down from 37 degrees C to 30 degrees C. We propose that the temperature dependent forms of p53-Val135 represent conformational variants of the p53 protein with opposing functions in cell growth control. PMID- 2258923 TI - Rotation function studies of human C-reactive protein. AB - Rotation function studies of two tetragonal crystal forms of human C-reactive protein have confirmed the pentameric structure of the molecule. The two crystal forms have space groups P4122 (I) and P4222 (II) with closely similar unit cells and are often twinned together. Investigation of the crystallization conditions indicates that dissociation heterogeneity has been a major limiting factor in the reproducible growth of good single crystals. The orientation of the pentameric molecule is shown to be almost identical in both forms, about the axial direction omega = 57 degrees, phi = 45 degrees, i.e. 57 degrees away from c in the (110) plane. PMID- 2258924 TI - Crystals of protein L1 from the 50 S ribosomal subunit of Thermus thermophilus. Preliminary crystallographic data. AB - Crystals have been obtained of protein L1 from the large ribosomal subunit of an extreme thermophile. Thermus thermophilus, using a mixed solution of ammonium sulphate/methane pentanediol. The crystals belong to the space group P2(1)2(1)2, with cell parameters a = 82.7 A, b = 63.4 A, c = 44.7 A. They diffract X-rays to 2.3 A resolution. PMID- 2258925 TI - Electron microscope investigation of the early stages of fibrin assembly. Twisted protofibrils and fibers. AB - Structures formed during the early stages of clot formation have been produced in a controlled manner by polymerization of soluble fibrin monomers prepared from dissolved normal clots that had been formed upon addition of thrombin to fibrinogen. In agreement with other studies using different approaches, electron microscopy of negatively contrasted or rotary-shadowed specimens of these preparations reveal two-stranded protofibrils, as well as shorter oligomers and fibrin monomers. Individual fibrin molecules are similar in appearance to fibrinogen, suggesting that no large-scale changes in conformation occur on removal of the fibrinopeptides. Moreover, these micrographs show details of the protofibril structure not previously seen. The visualization of clear cross-over points of the filaments making up the protofibril indicate that these structures are twisted. Diffraction patterns of electron micrographs of both protofibrils and fibers and computer modeling of protofibrils also suggest that these structures are twisted but not precisely ordered. PMID- 2258926 TI - Crystallization of the Fab from a human monoclonal antibody against gp 41 of human immunodeficiency virus type I. AB - A monoclonal IgG antibody directed against gp 41 from the human immunodeficiency virus (HIV-1) has been crystallized in both intact and Fab forms. Crystals of the intact antibody grow as tetragonal-like prisms too small for conventional X-ray analysis. However, the Fab portion of the antibody produces suitable plate-like crystals which belong to the space group P2(1)2(1)2(1) with unit cell constants of a = 66.5 A, b = 74.3 A and c = 105.3 A. There is one molecule of Fab in the asymmetric unit. The Fab crystals show diffraction to d-spacings less than 3.0 A. PMID- 2258927 TI - Crystallization and preliminary X-ray diffraction studies of a monoclonal antibody Fab fragment specific for an influenza virus haemagglutinin and of an escape mutant of that haemagglutinin. AB - Preliminary crystallographic data are given for two molecules involved in the interaction between the humoral immune response and the influenza virus. These molecules are the Fab fragment of an antibody specific for the haemagglutinin of influenza virus strain X31 (Hong Kong 1/68 (H3N2)) and a mutant of X31 haemagglutinin that escapes recognition by that antibody. Crystals of the haemagglutinin are isomorphous to those of X31, whose structure is known; they diffract to 3.4 A resolution. Crystals of the Fab fragment are trigonal with space group P3(1)21 (or P3(2)21) and diffract to 2.6 A resolution. The unit cell dimensions are a = b = 98.9 A, c = 89.2 A. A native data set has been collected for both proteins. PMID- 2258928 TI - Crystallization and preliminary X-ray diffraction studies of the N-terminal domain of the phosphorylating subunit of mannose permease from Escherichia coli. AB - Mannose permease is a constitutive component of the phosphotransferase system in Escherichia coli. This complex consists of two transmembrane subunits (II-PMan, Mr = 28,000 and II-MMan, Mr = 31,000) and a hydrophilic subunit (IIIMan). IIIMan functions as a phosphorylating enzyme and exists as a soluble homo-dimer of Mr = 70,000 in the cytosol. The N-terminal domain (P13) of IIIMan contains a phosphorylation site and the interface for dimerization. P13 has been crystallized in two different forms: type I, orthorhombic, space group C222 with a = 98.7 A, b = 106.5 A and c = 57.4 A, and type II, monoclinic, space group P2(1), with a = 54.4 A, b = 100.5 A, c = 58.1 A and beta = 90.5 degrees. Both types of crystal are suitable for X-ray diffraction studies. PMID- 2258929 TI - Human gamma-crystallin genes. A gene family on its way to extinction. AB - During hominoid evolution the gamma-crystallins of the lens have decreased in quantity as well as complexity, a change correlated with an increased water content of the lens. To trace the molecular basis for the decrease in gamma crystallin gene expression, we have characterized the structure and expression of the human gamma-crystallin gene family. We show that the human gamma-crystallin gene family consists of six complete genes (gamma A, gamma B, gamma C, gamma D, psi gamma E and psi gamma F) and one second exon fragment, the gamma G gene. Model experiments showed that, although the gamma G sequence is bordered by consensus splice sites, it is most likely transcriptionally inactive in the lens. In the human embryonic lens the gamma C and gamma D genes accounted for 81% of the gamma-crystallin transcripts, the gamma A gene contributed 14% and the gamma B gene only 5%. The composition of the gamma-crystallin mRNA pool changed only after birth, with the gamma D transcript as the only detectable transcript at ten years of age. The relative activities of the gamma A, gamma C and gamma D promoters in a transient expression system were in agreement with the ratio of their in vivo RNA levels, suggesting that the difference in accumulation of these transcripts is due to differences in the rate of transcription. The gamma B promoter was much more active than expected and had lost its tissue-specificity. Model experiments showed that the low yield of the gamma B transcript is due to post-transcriptional processes, most likely RNa instability mediated by third exon sequences. Together with previous data, our results show that the decrease in expression of the gamma-crystallin genes in the human lens is the consequence of gene loss (gamma G), inactivation of coding sequences (psi gamma E and psi gamma F), decrease in rate of transcription (gamma A), increase in rate of RNA turn-over (gamma B) and a delay in the onset of transcription during development. PMID- 2258930 TI - Structural organization of Acheta rDNA. Evidence for differential amplification of soma and germ-line-specific rDNA sequences. AB - Amplification is one of the mechanisms whereby the expression of genes can be specifically reinforced. Ribosomal gene amplification in amphibian and insect oocytes is a particularly well documented case. We studied heterogeneity, amplification and size of Acheta domesticus (insects; Orthoptera) ribosomal DNA and characteristics of male and female somatic or germ line rDNAs by analysis of genomic clones from a conventional and a microclone library. The length of the Acheta rDNA repeat unit (transcription unit and non-transcribed spacer (NTS] varied from 47 x 10(3) to 60 x 10(3) base-pairs, with highest variability within the NTS region. Deletions, fragment length heterogeneity and size variability in small steps of individual NTS segments are responsible for the observed size variation. The number of rDNA repeat units per haploid genome of Acheta was determined as 190(+/- 10%). The rDNA is amplified 14(+/- 10%)-fold in the oocyte, producing about 10,000 gene copies per cell. Our results show that the amplification mechanism does not favor individual fragments within the repeat unit. Thus, it can be concluded that amplification does not change the chromosomal characteristics of the rDNA pool. Two fragments specific for oocyte rDNA suggest that the rearrangements accompanying amplification are preferentially located in one distinct EcoRI fragment. Certain regions of Acheta rDNA contain cell-type-specific fragments: it was thus possible to characterize one purely male fragment and a second one specific for male and female soma but not for germ line rDNA. We show that Acheta rDNA reveals a combination of many features reported from different organisms and novel tissue-specific alterations on an extremely large repeat unit. The tissue-specific alterations indicate sexual and soma/germ line differentiation events that are derived by as yet unknown mechanisms. PMID- 2258931 TI - Structure and expression of the Aplysia californica calmodulin gene. AB - We have isolated and characterized the calmodulin (CaM) gene of the marine mollusc Aplysia californica. Its primary structure, deduced from the nucleotide sequence of the gene, is highly conserved, containing only three amino acid substitutions compared to the CaM of higher vertebrates. The structural gene consists of four exons that encode the protein, 3' non-translated mRNA and at least one additional exon encoding 5' non-translated mRNA and the initiator methionine. A comparison of the exon/intron structure of CaM genes from several organisms shows conservation of intron position, suggesting that introns have been both inserted and deleted during evolution. Northern analysis of RNA prepared from several Aplysia tissues reveals the presence of several CaM mRNA transcripts with the greatest expression observed in neural and muscle tissue. One of these transcripts is abundant only in mRNA prepared from nervous tissue. PMID- 2258932 TI - Concerted evolution of primate alpha satellite DNA. Evidence for an ancestral sequence shared by gorilla and human X chromosome alpha satellite. AB - To understand evolutionary events in the formation of higher-order repeat units in alpha satellite DNA, we have examined gorilla sequences homologous to human X chromosome alpha satellite. In humans, alpha satellite on the X chromosome is organized as a tandemly repeated, 2.0 x 10(3) base-pairs (bp) higher-order repeat unit, operationally defined by the restriction enzyme BamHI. Each higher-order repeat unit is composed of 12 tandem approximately 171 base-pair monomer units that have been classified into five distinct sequence homology groups. BamHI digested gorilla genomic DNA hybridized with the cloned human 2 x 10(3) bp X alpha satellite repeat reveals three bands of sizes approximately 3.2 x 10(3), 2.7 x 10(3) and 2 x 10(3) bp. Multiple copies of all three repeat lengths have been isolated and mapped to the centromeric region of the gorilla X chromosome by fluorescence in situ hybridization. Long-range restriction mapping using pulsed field gel electrophoresis shows that the 2.7 x 10(3) and 3.2 x 10(3) bp repeat arrays exist as separate but likely neighboring arrays on the gorilla X, each ranging in size from approximately 200 x 10(3) to 500 x 10(3) bp, considerably smaller than the approximately 2000 x 10(3) to 4000 x 10(3) bp array found on human X chromosomes. Nucleotide sequence analysis has revealed that monomers within all three gorilla repeat units can be classified into the same five sequence homology groups as monomers located within the higher-order repeat unit on the human X chromosome, suggesting that the formation of the five distinct monomer types predates the divergence of the lineages of contemporary humans and gorillas. The order of 12 monomers within the 2 x 10(3) and 2.7 x 10(3) bp repeat units from the gorilla X chromosome is identical with that of the 2 x 10(3) bp repeat unit from the human X chromosome, suggesting an ancestral linear arrangement and supporting hypotheses about events largely restricted to single chromosome types in the formation of alpha satellite higher-order repeat units. PMID- 2258933 TI - Subrepeats result from regional DNA sequence conservation in tandem repeats in Chironomus telomeres. AB - Repeat units, widespread in eukaryotic genomes, are often partially or entirely built up of subrepeats. Homogenization between whole repeat units arranged in tandem usually can best be understood as a result of unequal crossing over. Such a mechanism is less plausible for maintaining similarities between subrepeats within a repeat unit when present in a regular array. In Chironomus telomeres, large blocks of tandemly repeated approximately 350 base-pair units contain two or three pairs of subrepeats with high mutual identities, embedded in linker DNA, non-repetitive within the repeat unit. Measurements of evolutionary base changes in two closely related species, Chironomus tentans and Chironomus pallidivittatus, permit us to conclude that the subrepeat arrangement is best explained as a consequence of regional sequence conservation after an earlier duplication of an ancestral half-unit. PMID- 2258934 TI - Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. AB - Alignment of the 87 available sequences of group I self-splicing introns reveals numerous instances of covariation between distant sites. Some of these covariations cannot be ascribed to historical coincidences or the known secondary structure of group I introns, and are, therefore, best explained as reflecting tertiary contacts. With the help of stereochemical modelling, we have taken advantage of these novel interactions to derive a three-dimensional model of the conserved core of group I introns. Two noteworthy features of that model are its extreme compactness and the fact that all of the most evolutionarily conserved residues happen to converge around the two helices that constitute the substrate of the core ribozyme and the site that binds the guanosine cofactor necessary for self-splicing. Specific functional implications are discussed, both with regard to the way the substrate helices are recognized by the core and possible rearrangements of the introns during the self-splicing process. Concerning potential long-range interactions, emphasis is put on the possible recognition of two consecutive purines in the minor groove of a helix by a GAAA or related terminal loop. PMID- 2258935 TI - Identification of a variable region of the African swine fever virus genome that has undergone separate DNA rearrangements leading to expansion of minisatellite like sequences. AB - Nucleotide sequencing identified a tandemly repeated sequence array 22 x 10(3) base-pairs from the right-hand DNA terminus of the African swine fever virus (ASFV) genome. The sequence of the repeat array and sequences closely flanking it were compared in the genomes of four groups of ASFV isolates that had very different restriction enzyme site maps. Arrays present in one group of ASFV isolates from East Zambia/Malawi varied in length and contained between 8 and 38 copies of a 17-nucleotide repeat unit. Repeat arrays in a second group of ASFV isolates from Europe were less variable in length but consisted of different types of repeat unit that were divergent in sequence. A third genetically diverse ASFV isolate. LIV 13 from a South Zambia Game Park, contained repeat unit types that were similar to those of European viruses. MFUE6 isolate from an East Zambia Game Park contained a shorter version of the European repeat unit. An eight-base pair core sequence was conserved between the East Zambia/Malawi and European and LIV 13 repeat units. These tandemly repeated sequence arrays share a number of properties with chromosomal minisatellite DNA. Similar tandem repeat arrays have not been described in poxviruses. PMID- 2258936 TI - Novel second-site suppression of a cold-sensitive defect in phage P22 procapsid assembly. AB - The DNA packaging portal of the phage P22 procapsid is formed of 12 molecules of the 90,000 dalton gene 1 protein. The assembly of this dodecameric complex at a unique capsid vertex requires scaffolding subunits. The mechanism that ensures the location of the 12-fold symmetrical portal at only one of the 12 5-fold vertices of an icosahedral virus capsid presents a unique assembly problem, which, in some viruses, is solved by the portal also acting as initiator of procapsid assembly. Phage P22 procapsids, however, are formed in the absence of the portal protein. The 1-csH137 mutation prevents the incorporation of the portal protein into procapsids. In a mixed infection with cs+ phage, the mutant subunits are able to form functional portals, suggesting that the cold sensitivity does not affect portal-portal interactions, but affects the interaction of portal subunits with some other molecular species involved in the initiation of portal assembly. Interestingly, the cs defect is suppressed by temperature-sensitive folding mutations at four sites in the P22 tailspike gene 9. The suppression is allele-specific; other tailspike tsf mutations fail to suppress the cs defect. Translation through a suppressor site is required for suppression. This observation is unexpected, since analysis of nonsense mutations in this gene indicates that it is not required for procapsid assembly. Examination of the nucleic acid sequences in the neighborhood of each of the suppressor sites shows significant sequence similarity with the scaffolding gene translational initiation region on the late message. This supports a previously proposed model, in which procapsid assembly is normally initiated in a region on the late messenger RNA that includes the gene 8 start site. By this model, the suppressor mutations may be acting through protein-RNA interactions, changing sequences that identify alternative or competing sites at which the mutant portal subunits may be organized for assembly into the differentiated vertex of the phage capsid. PMID- 2258937 TI - Complex between single-stranded DNA and gene 5 protein of bacteriophage M13 studied with linear dichroism and ultraviolet absorption. AB - We have studied complexes between the gene 5 protein (gp5) of bacteriophage M13 and various polynucleotides, including single-stranded DNA, using ultraviolet absorption and linear dichroism. Upon complex formation the absorption spectra of both the protein and the polynucleotides change. The protein absorption changes indicate that for at least two of the five tyrosine residues per protein monomer the environment becomes less polar upon binding to the polynucleotides but also to the oligonucleotide p(dT)8. All gp5-polynucleotide complexes give rise to intense linear dichroism spectra. These spectra are dominated by negative contributions from the bases, but also a small positive dichroism of the protein can be discerned. The spectra can be explained by polynucleotide structures, which are the same in all complexes. The base orientations are characterized by a substantial inclination and propellor twist. The number of possible combinations of inclination and propeller twist values, which are in agreement with the linear dichroism results, is rather limited. The base orientations with respect to the complex axis are essentially different from those in the complex with the single stranded DNA-binding protein gp32 of bacteriophage T4. PMID- 2258938 TI - Three-dimensional reconstruction of native Androctonus australis hemocyanin. AB - A sample of native 4 x 6-meric hemocyanin of Androctonus australis was negatively stained with the double-layer technique, and was observed by transmission electron microscopy under low-dose conditions with a 50 degree and 0 degree tilt. The three-dimensional reconstruction method from "Single-exposure, random conical tilt series" was then applied. Independent three-dimensional reconstructions were obtained from the top, side and 45 degree views. Despite a pronounced flattening effect, presumably due to the specimen preparation technique, the positions of the 24 subunits composing the oligomer were unequivocally determined. This experiment definitely solves the problem of the architectural organization of the subunits in the cheliceratan 4 x 6-meric hemocyanins. Moreover, distinction between the flip and flop faces and an attenuated rocking effect were observed. PMID- 2258939 TI - Molecular and crystal structure of d(CGCGmo4CG): N4-methoxycytosine.guanine base pairs in Z-DNA. AB - The base analogue N4-methoxycytosine (mo4C) is ambivalent in its hydrogen-bonding potential, since it forms stable base-pairs with both adenine and guanine in oligomer duplexes. To investigate the base-pair geometry, the structure of d(CGCGmo4CG) has been determined by single-crystal X-ray diffraction techniques. The d(CGCGmo4CG)2 crystallized in a left-handed double helical structure (Z type). Refinement using 2559 reflections between 10 and 1.7 A converged with a final R = 0.181 (Rw = 0.130) including 68 solvent molecules. The orthorhombic crystals are in the space group P2(1)2(1)2(1), with cell dimensions a = 18.17 A, b = 30.36 A, c = 43.93 A. The mo4C.G base-pair is of the wobble type, with mo4C in the imino form, and the methoxy group in the syn configuration. PMID- 2258940 TI - Reverse turns in blocked dipeptides are intrinsically unstable in water. AB - We have carried out molecular dynamics simulations to study the conformational equilibria of two blocked dipeptides, Ac-Ala-Ala-NHMe and trans-Ac-Pro-Ala-NHMe, in water (Ac, amino-terminal blocking group COCH3; NHMe, carboxy-terminal blocking group NHCH3). Using specialized sampling techniques we computed free energy surfaces as functions of a conformation co-ordinate that corresponds to hydrogen-bonded reverse turns at small values and to extended conformations at large values. The free-energy difference between hydrogen-bonded reverse turn conformations and extended conformations, determined from the equilibrium constants for reverse turn unfolding, is approximately -5 kcal/mole for Ac-Ala Ala-NHMe, and -10 kcal/mole for Ac-Pro-Ala-NHMe. These results demonstrate that reverse turns in blocked dipeptides are intrinsically unstable in water. That is, in the absence of strongly stabilizing sequence-specific inter-residue interactions involving side-chains and/or charged terminal groups, the extended conformations of small peptides are highly favored in solution. By thermodynamically decomposing the free-energy differences, we found that the peptide-water entropy is the primary reason for the exceptional stability of the extended conformations of both peptides, and that the differences between the two peptides are primarily due to differences in the peptide-water interactions. In addition, we assessed the "proline effect" on the conformational equilibria by comparing the differences in configurational entropies between the reverse turn and extended conformations of the two peptides. As expected, the extended conformation of the Pro-Ala peptide is destabilized by reduced configurational entropy, but the effect is negligible in the blocked dipeptides. Finally, we compared our results with the results of several other experimental studies to identify some of the specific interactions that may be responsible for stabilizing reverse turns in small peptides in solution. PMID- 2258941 TI - NASCIS. National Acute Spinal Cord Injury Study. PMID- 2258942 TI - Methylprednisolone in spinal cord injury: the possible mechanism of action. PMID- 2258943 TI - Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat. AB - A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258945 TI - Traumatic brain injury creates biphasic systemic hemodynamic and organ blood flow responses in rats. AB - Traumatic brain injury affects systemic circulation as well as directly damages the brain. The present study examined the effects of fluid percussion brain injury on systemic hemodynamics and organ arterial blood flow in rats. Rats were prepared for fluid percussion injury under anesthesia. Twenty-four hours later, rats were anesthetized (1.0% halothane in N2O:O2) and prepared for radioactive microsphere measurement of cardiac output and organ blood flow. After baseline blood flow and physiological measurements were established, the rats were injured (2.47 +/- 0.02 atm, n = 17) or not injured (n = 20). Additional blood flow determinations were made at two of the following four time (T) points: 5, 15, 30, and 60 min after the injury or sham injury. Fluid percussion brain injury produced an immediate systemic hypertension followed by a hypotension and low cardiac output. Organ blood flows remained constant or increased for 30 min and then declined. Decreased blood flow was most pronounced in the kidneys and the spleen and was less severe in the liver. The reduced cardiac output was redistributed to favor blood flow through the heart and pancreas. These data suggest that traumatic brain injury creates a hyperdynamic period followed by a hypodynamic state with a heterogeneous hypoperfusion among organs. PMID- 2258944 TI - Protective effect of MK801 in experimental brain injury. AB - The effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK801, was studied in a model of closed head injury in rats. Head trauma (HT) was induced over the left cerebral hemisphere by a calibrated weight-drop device. One or 3 h later, MK801 in saline was given i.p. in a single bolus of either 1, 3, or 10 mg/kg. The rats were killed at 4, 24, or 48 h after HT. Cortical tissue samples were taken from the injured zone and from the corresponding region of the contralateral hemisphere and analyzed for specific gravity (SG) by linear gradient columns. The neurological status of the traumatized rats was evaluated by a neurological severity score (NSS) 1 h after trauma and just before death. Pathological evaluation, based on size and severity of the lesion, was performed 24 and 48 h after HT on control and MK801-treated rats. A dose of 3 mg/kg MK801 given 1 h after trauma effectively prevented the reduction in tissue SG only at 24 h. The NSS could not be evaluated at 24 h after trauma because of the sedating effect of the drug. At 48 h posttrauma, however, the drug significantly improved the neurological state of the rats. No significant difference was found in the pathological score between treated and untreated rats. The results demonstrate neuroprotective properties of MK801, as expressed in two different variables- reduced edema formation and improved neurological recovery after HT. These findings support existing evidence that pharmacological intervention with NMDA receptor antagonist after head injury may be of clinical value in the management of head-injured patients. PMID- 2258946 TI - Neuropathological changes and neurological function after spinal cord compression in the rat. AB - As part of a series of experimental investigations of the effects of various pharmacological agents on the outcome of compressive spinal cord trauma in the rat, the time course of the cell changes in the cord at the site of and distal to the compression was studied at the light microscopic level. The degree of compression used with the present model results in a transient paraparesis that recovers almost completely over a period of 3 weeks as judged by the inclined plane technique. The most significant morphological findings were as follows. Initially (1 and 24 h after the impact) there was pronounced swelling and hemorrhage at the compression site, chiefly in the gray matter of the cord. On day 4 there was severe necrosis in the same region, with numerous macrophages and leukocytes. Rats killed after 21 days showed either minor residual signs of necrosis or essentially normal tissue architecture. Surprisingly, necrosis with delayed onset also developed in the dorsal columns, involving the pyramidal tracts. This necrosis was detected in animals killed after 9 and 21 days but not in those observed after 4 days or earlier. The longitudinal tracts of the white matter showed reduced staining in paraffin sections of the compression site. Epon sections revealed splits in the myelin sheaths and enlarged periaxonal spaces as early as 1 h after the impact. The alterations in the longitudinal tracts persisted throughout the 21-day observation period and extended down to L2-L4. There was gradual functional recovery, documented by the inclined plane test. Preinjury values were almost reached on day 21, although the cord still showed some morphological damage. In individual animals, no relation was found between degree of function as tested by inclined plane and extent of morphologic injury. Additional functional and morphological methods obviously are needed in future investigations of the effects of treatments on the outcome of compressive spinal cord injury. PMID- 2258947 TI - Neuronal survival and dynamics of ultrastructural damage after dendrotomy in low calcium. AB - To determine the contributions of calcium to development of ultrastructural damage and neuronal death after mechanical injury, we amputated primary dendrites from over 300 cultured mammalian spinal neurons under normal (1.8 mM) or low (less than or equal to 30 microM) calcium conditions. Two general categories of early ultrastructural change were seen in both normal and low calcium: (1) a lesion-dependent gradient of damage that moved centripetally through the proximal segment and penetrated the soma within 15 min and (2) dilation of the somal Golgi/smooth endoplasmic reticulum (SER), which preceded the wave of deterioration from the lesion. Although the somal Golgi/SER changes were similar in both normal and low calcium, the damage gradient in low calcium differed from the damage gradient in normal calcium. (1) Microtubules and neurofilaments were preserved, (2) mitochondria became more electron dense but did not develop electronlucent foci or high amplitude swelling, and (3) an extensive vesicular gradient formed consisting of rows of swollen SER vesicles. Sodium ionophores have been reported to cause similar changes. Survival studies showed that calcium reduction significantly delayed neuronal death. Survival was 63 +/- 16% vs 35 +/- 8% (p less than 0.003) at 2 h and 30 +/- 7% vs 23 +/- 8% at 6 h in low and normal calcium, respectively. Dead neurons that had been lesioned in low calcium also showed greater ultrastructural preservation than neurons that died after dendrotomy in normal calcium. We hypothesize that under low calcium conditions, the large sodium injury current plays an important role in neuronal deterioration and death after mechanical trauma. PMID- 2258948 TI - A threat to autologous blood donors. PMID- 2258949 TI - The survival of Afro-American physicians in 1990 and beyond: inaugural address. PMID- 2258950 TI - Transplantation and the trauma surgeon. AB - The number of satisfactory vascular organs suitable for organ transplantation can be increased appreciably by a close working relationship between traumatologists and transplant surgeons. Benefits will derive from more precise and rapid field management of brain-injured patients, with subsequent appropriate stabilization. If brain death is declared, prompt referral for organ donation with optimal management should result in well-functioning organs for transplantation. A defined team approach with well-defined protocols could solve most of the medical and moral dilemmas. Compassionate emotional support should be provided for families, particularly minorities, and should extend to inexperienced staff. Underlying these goals are a strong institutional commitment to staff education and an understanding of the lifesaving role that organ transplantation can play. PMID- 2258951 TI - Death, AIDS morbidity, and HIV seroprevalence in New York City intravenous drug abusers. AB - Drug treatment programs represent a point of access to intravenous drug abusers and, as such, may also be useful in monitoring health status indicators among this population. Such a surveillance project was established in 1985 among drug treatment clinics in New York City to monitor the human immunodeficiency virus (HIV) epidemic. HIV seroprevalence was 54% (255/469) in 1985, 61% (159/262) in 1986, and 60% (133/222) in 1987. Of the 2500 cumulative enrollees in these clinics each year, 4 patients met the Centers for Disease Control acquired immunodeficiency syndrome (AIDS) surveillance definition in 1985, 37 in 1986, and 37 in 1987. There were 25 AIDS-related deaths in 1985, 8 in 1986, and 16 in 1987. These results suggest that by including drug treatment programs in a rational surveillance system, we may be able to monitor the HIV epidemic more closely. The public health significance of such a surveillance program is magnified given the association between intravenous drug abuse-associated AIDS and the prevalence of AIDS among women, children, and ethnic/racial minorities. PMID- 2258952 TI - Current status of prostate cancer in North American black males. AB - The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program is used to examine the most recent data available to draw inferences about black and white males in the United States with prostate cancer. Findings include a continuing rise in the incidence of prostate cancer which, as of 1985 SEER data, is 50% higher in the black male population than in white males. With the exception of minor fluctuations over the last 17 years, the mortality rate for black males demonstrates an upward trend. Combining all stages and ages, the survival rate for black males is 10% poorer than for white males. These data provide a glimpse into the problem of prostatic carcinoma in the United States today. To develop preventive strategies and cancer control interventions, a fuller understanding of the nature of the disease and its biologic course is necessary. Epidemiologic questions concerning socioeconomic status among and within racial groups, lifestyles, and behaviors that affect health seeking and diagnosis and treatment of prostatic cancer must be answered. By examining SEER data for prostatic cancer, we update the current status of this disease in North American blacks and infer possible directions for future epidemiologic surveys and cancer control intervention research. PMID- 2258953 TI - Supplemental emergent chest computed tomography in the management of blunt torso trauma. AB - The efficacy of conventional chest X-ray (CXR) in comparison to chest computed tomography (CCT) in acutely injured blunt trauma patients was examined. Over a 21 month period, 50 patients underwent CXR and CCT according to a standard protocol, and their films and records were reviewed retrospectively. Hemo- and/or pneumothorax (HPTX) was noted in 12 patients (five by CXR, 12 by CCT). Pulmonary contusion (PC) was identified in ten patients (four by CXR, ten by CCT). Three additional false positive PC were diagnosed by CXR. Therapy changes based upon CCT findings occurred in seven of seven HPTX and five of six PC. The two imaging techniques were complementary in detecting fractures. Atelectasis was a common CCT finding (58% incidence). Chest X-ray is less sensitive than chest computed tomography in the detection of HPTX (42% vs. 100%) and PC (40% vs. 100%). Emergent chest computed tomography is recommended in stable patients with: 1) blunt high-energy torso trauma, 2) "cross-body" injury pattern, and/or 3) a mechanism of injury suggestive of chest trauma. PMID- 2258954 TI - Continuous arteriovenous rewarming: experimental results and thermodynamic model simulation of treatment for hypothermia. AB - We evaluated a technique for treating hypothermia that uses extracorporeal circulation but does not require heparin or pump assistance. Hypothermia to 29.5 degrees C was induced in eight anesthetized dogs, and thermistors placed in the pulmonary artery, liver, bladder, esophagus, rectum, muscle, and skin. Four experimental animals were rewarmed by creating a fistula which connected arterial and venous femoral lines to an interposed counter-current heat exchanger. External rewarming was used in four controls. Bleeding time (BT), coagulation profile (PT, PTT, TT), and cardiac output (CO) were measured during rewarming. Core temperature (T) rose significantly faster with CAVR (0.00001). Average time to rewarming was 45 min, vs. 4 hrs in controls. Haptoglobin, platelet, fibrinogen, and fibrin split product levels were unaffected. Continuous arteriovenous rewarming (CAVR) improved T, CO, BT, and coagulation profile faster than any method yet reported not requiring heparin or cardiac bypass. The application of CAVR in post-traumatic hypothermia warrants further investigation. PMID- 2258955 TI - Penetrating iliac vascular injuries: recent experience with 233 consecutive patients. AB - During a recent 11-year period, 233 consecutive patients with 358 penetrating iliac vascular injuries were treated at our institution. Injuries of the common and external iliac arteries were most often repaired with lateral suture (31%) although several other techniques were also employed. Lateral suture and ligation were used with nearly equal frequency in the management of venous injuries. The hospital mortality rate for the series was 28%, and 56/66 deaths (85%) were due to exsanguination or shock. One patient, initially treated with an end-to-end anastomosis of the iliac artery, died a year after discharge from a ruptured false aneurysm. Two patients treated with lateral suture of venous injuries died of pulmonary embolism. Arterial complications occurred in 15% of patients with arterial injuries and three patients required amputation. No graft infections occurred in 16 patients treated with PTFE interpositions, including four with associated colorectal injuries. Venous complications occurred in 12% of patients with venous injuries, and most were noted in those treated with ligation. Four patients treated by venous ligation developed chronic venous insufficiency. The prevention of death from exsanguination is the greatest problem in the management of patients with iliac vascular injuries. Although some late deaths and many complications may be related to the technique of vascular repair, circumstances often prohibit alternative methods. Despite two deaths from pulmonary embolism, insufficient data exist to condemn lateral suture of venous injuries. PMID- 2258956 TI - The management of flail chest injury: factors affecting outcome. AB - The records of 57 patients presenting with flail chest injury from 1981 through 1987 were reviewed to determine factors affecting morbidity and mortality. Fifteen patients (26%) had 8+ rib fractures with a unilateral flail and seven (12%) had multiple rib fractures with a bilateral flail. Thirty-two (56%) had moderate-severe pulmonary contusions and 44 (77%) required chest tubes for hemo pneumothorax. Ventilatory assistance was used in 36 (63%). The major factors determining the need for ventilatory assistance were: an ISS greater than or equal to 23, blood transfusions in the first 24 hours, moderate-severe associated injuries (fractures, head injuries or truncal organs requiring operation), and shock on admission (p less than 0.001). An adverse outcome occurred in 15 (28%); nine required ventilatory assistance greater than or equal to 14 days and six died of sepsis with pneumonia. The main factors associated with an adverse outcome were: an ISS greater than or equal to 31 (p less than 0.001), moderate severe associated injuries (p less than 0.001), and blood transfusions (p less than 0.005). Although the primary determinants of an adverse outcome were the associated injuries and blood loss, a bilateral flail (p less than 0.01) and age greater than or equal to 50 years (p less than 0.02) were contributing factors. PMID- 2258957 TI - Conservative management of duodenal trauma: a multicenter perspective. AB - The experience of eight trauma centers with duodenal injuries was analyzed to identify trends in operative management, sources of duodenal-related morbidity, and causes of mortality. During the 5-year period ending December 1988, 164 duodenal injuries were identified. Patient ages ranged from 5 to 78 years. There were 38 Class I, 70 Class II, 48 Class III, four Class IV, and four Class V injuries. Injury mechanism was penetrating in 102 (62%) patients and blunt in 62. Primary repair of the duodenal injury was performed in 117 (71%) patients, including 27 patients also managed with pyloric exclusion and 12 with tube duodenostomy. Duodenal resection with primary anastomosis was used in six (4%) patients and pancreatoduodenectomy was necessary in five (3%). There were 30 (18%) deaths. The cause of death was uncontrolled hemorrhage from severe hepatic or vascular injuries in 22 (73%) patients. In only two (1%) patients could death be attributed to the duodenal injury; each as the result of duodenal repair dehiscence and subsequent sepsis. Duodenal-related morbidity was documented in 29 (18%) patients, including 22 patients with intra-abdominal abscess, six with duodenal fistula, and five with frank duodenal dehiscence. In summary, this analysis demonstrated: 1) the great majority of duodenal injuries can be managed by simple repair; 2) tube duodenostomy is not a mandatory component of operative treatment; 3) pyloric exclusion is a useful adjunct for more complex injuries; 4) pancreatoduodenectomy is rarely necessary for civilian duodenal trauma; 5) morbidity following duodenal trauma is more dependent on associated intra abdominal injuries than the extent of duodenal trauma; and 6) mortality following duodenal injuries is primarily related to associated vascular and hepatic trauma. PMID- 2258958 TI - Mortality in trauma patients: the interaction between host factors and severity. AB - Data on host factors influencing mortality in trauma patients is sparse and contradictory. To develop a model for health policy decisions, we examined all trauma admissions to acute care hospitals in the state of California in the year 1986. We looked at the influence of the following host factors: age, gender, and preinjury medical conditions, on mortality stratified by injury severity. The study group (N = 199,737) had an overall mortality rate of 1.9%. Mortality increased starting at age 40 years and was independently influenced by gender, the presence of pre-existing disease, and the body region injured. In patients with minor injury, mortality rates became higher in the elderly at age 65+. However, in patients with injuries of moderate severity, mortality increased in both middle age (40-64) and elderly groups (65+). Male gender was also a risk factor, present in both the elderly and middle age groups. While the presence of both pre-existing medical disease or injury to head or abdomen was related to increased mortality in middle-aged patients at all severity levels, neither accounted for the effect of gender. Conclusion. Age and gender influence mortality in trauma patients. These effects are not explained by documented pre existing disease or region of injury. Age and gender serve only as observable markers for subgroups of patients with impaired response to injury. Middle-aged males comprise a previously unrecognized high-risk subgroup for this impaired response. PMID- 2258959 TI - The management of large soft-tissue defects following close-range shotgun injury. AB - Large soft-tissue defects following close-range shotgun blasts remain a major technical challenge to trauma surgeons. During the period 1980 through 1988, 43 patients who survived greater than 48 hours following this injury were managed in our center. The locations of their soft-tissue defects were: extremity, 22; abdomen/chest, 18; and head/neck, three. All patients underwent immediate surgical exploration and wide debridement of all devitalized tissue along with repair of associated injuries. Management included mandatory frequent dressing changes, debridement, irrigation in the operating room, and the perioperative administration of broad-spectrum antibiotics. Four patients whose abdominal wall defects could not be initially closed had temporary placement of rayon cloth to prevent evisceration. Overall, four patients underwent delayed primary closure, eight were covered with split-thickness skin grafts, nine had closure with myocutaneous flaps, and 19 closed by secondary intent. Two patients, who were transferred to us following initial management, developed wound sepsis due to inadequate debridement and both eventually required amputation as did one patient who developed early myonecrosis following lengthy arterial repair. Frequent operative dressing changes, adequate debridement, and irrigation minimize sepsis following close-range shotgun blasts and should be the treatment of choice for this devastating injury. Techniques of wound closure need to be individualized to the particular situation. PMID- 2258960 TI - Nonoperative management of blunt liver injuries in adults: the need for continued surveillance. AB - Computed tomography (CT) scanning after blunt abdominal trauma has allowed nonoperative management of selected patients with liver injuries. This report describes 52 adult patients with liver injuries who were treated without immediate surgery. Thirty-four of these hepatic injuries were relatively minor (Grade I-II), and 18 were considered major (Grade III-V). Free intraperitoneal blood in small to large amounts was evident on CT in 37 patients. There were no deaths in this series, no major complications, no known missed intra-abdominal injuries, and no delayed hemorrhage. While most liver injuries appear to heal rapidly by serial CT scans, a small percentage of these patients have residual liver defects persisting for several months and may be at risk for future complications. PMID- 2258961 TI - Dynamic computerized tomography of the occiput-atlas-axis complex in trauma patients with odontoid lateral mass asymmetry. AB - Over a 23-month period, 25 patients aged 11 to 74 years presented to our Level I trauma center with odontoid lateral mass asymmetry of 2 to 5 mm on properly centered AP open-mouth X-rays: 32% of patients were asymptomatic, 68% had cervical pain, and 32% had limited range of motion. Patients with cervical spine fractures or dislocations and those with fixed deformity were excluded. The clinical significance of asymmetry was determined utilizing dynamic axial CT scanning of the occiput (C0), atlas (C1) and axis (C2) with the head neutral and with 15 degrees to 30 degrees active rotation. Nineteen patients demonstrated greater than 5 degrees of relative motion of C1 on C2 bilaterally. Three patients had less than 5 degrees of relative motion bilaterally and three patients had less than 5 degrees relative motion with left rotation only. No patient had formal treatment and all had nearly normal cervical range of motion on clinical examination at the time of hospital discharge. The finding of an asymmetric odontoid-lateral mass interspace on properly centered open-mouth AP X-rays in the presence of otherwise normal cervical spine X-rays, in conscious patients without fixed deformity, appears to be incidental and requires no further evaluation or treatment. PMID- 2258962 TI - Complications in evaluating abdominal trauma: diagnostic peritoneal lavage versus computerized axial tomography. AB - We reviewed our experience with 2,809 DPL's and 1,331 CT's obtained in the resuscitative phase over a 3-year period in our trauma system to determine the significant complications associated with each modality. There were 25 DPL complications: eight false negatives, three false positives, and 14 technical errors. There were 46 CT complications including 25 false negative scans, three false positive scans, and 18 delays to the operating room from obtaining abdominal CT evaluation, with two of these delays resulting in preventable deaths. Although both modalities had low complication rates (0.9% DPL vs. 3.4% CT), DPL was associated with less preventable mortality and morbidity than CT in the evaluation of abdominal trauma. PMID- 2258963 TI - The morbidity and financial impact of colostomy closure in trauma patients. AB - During a 10-year period, 87 patients who had undergone elective colostomy closure at Bellevue Hospital were retrospectively reviewed in order to evaluate the morbidity of colostomy closure after traumatic injury and its financial impact. Sixty-two per cent of the colostomies were in the left colon and 38% were right sided. The interval from the original injury to colostomy takedown varied from 20 to 465 days, with a mean of 144 days. The mean postoperative hospital stay for the entire group was 15.13 days at a cost of $13,995. There were no deaths and no anastomotic leaks in the entire series, but a morbidity rate of 25% ensued. Small bowel obstruction was the most frequent significant complication, occurring in ten patients (11.5%) and resulting in a prolongation of hospital stay by 7 days at an additional cost of $6,500 per patient. One additional patient developed a subphrenic abscess which required operative drainage, necessitating an additional 24 days in the hospital at an increased cost of $22,200. Other complications which did not prolong hospital stay included eight superficial wound infections, one transient respiratory failure, and two patients who returned at a later date with incisional hernias at the stoma site. The 25% morbidity encountered in this series suggests that colostomy closure is not a low-morbidity procedure and should be considered as an important factor favoring primary repair. Coupled with the significant financial impact of both colostomy formation and takedown, ample justification exists for greater efforts in avoiding colostomy formation whenever feasible. PMID- 2258964 TI - Blunt carotid artery dissection: incidence, associated injuries, screening, and treatment. AB - Blunt carotid dissection (BCD) is a rare injury occurring in less than one in 1,000 victims of blunt injuries. Using a 4-year experience in a trauma system with 14 cases of BCD, we performed a matched blunt trauma patient case-control analysis to determine if there were patterns of injuries that were associated with increased risk of BCD. Patients with combinations of head, facial, and cervical spine injuries with or without extremity fractures proved to be at significantly increased risk for BCD. Duplex scanning appears to be a useful screening tool for these patients. Anticoagulation was the preferred treatment once neurologic deficits were present. PMID- 2258965 TI - The effect of alcohol in isolated blunt splenic trauma. AB - The effect of alcohol on trauma patients is controversial, with numerous authors citing no difference in mortality in acutely intoxicated patients. The purpose of our study was to retrospectively investigate the effect of alcohol in adult patients with isolated blunt splenic injury. From 1980 through 1989, 47 adult patients with splenic trauma as the only major injury were admitted to the Trauma Service. There were 37 males and ten females with a mean age of 29 years (range, 15 to 61). Motor vehicle accidents were responsible for 44 (94%) of the injuries. Group 1 consisted of 24 patients with a mean blood alcohol level of 185 mg/dl (range, 15 to 380). In Group 2 there were 23 patients without detectable blood alcohol. There were no statistically significant differences between the two groups in age, Abbreviated Injury Severity Score, initial hematocrit, and grade of splenic injury. Hypotension was present in 13 patients (55%) in Group 1 versus six patients (26%) in Group 2 (p less than 0.05). Significant abnormalities in clotting studies were present on admission in six patients (25%) in the alcohol detected group versus one in the other group (p less than 0.05). Blood transfusion requirements in the first 24 hours were significantly greater in Group 1 (mean, 3.9 units) versus Group 2 (mean, 0.5 units) (p less than 0.001). If alcohol was present, there was much less chance for splenic conservation, as 18 patients (75%) underwent splenectomy versus seven patients (30%) in the nonalcohol group (p less than 0.05). There was one death and this occurred in a patient acutely intoxicated who suffered a cerebral infarct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258967 TI - Unintentional injury death rates in rural Appalachia. AB - Rural unintentional injury (UI) death rates are higher than rates for urban regions. Our trauma center serves 49 rural Appalachian (AP) counties in a 120 county rural state. We investigated the impact of prehospital and hospital resources on UI death rates in our referral area. Age-adjusted and average age- and sex-specific UI death rates from 1979-1985 were compared among 49 rural AP counties, the 71 non-Appalachian (NAP) counties, and the United States. Counties were grouped for comparisons by level of prehospital care (Advanced Life Support [ALS] vs. Basic Life Support [BLS]) and by presence (H) or absence (NH) of a hospital. Death rates were calculated using data from the 1980 population census, the National Center for Health Statistics (NCHS), and state vital statistics. Within AP, all 49 counties have ambulance service. Only 9/49 (18%) have ALS service and 13/49 (26%) have no hospital. Age-specific AP rates were higher than NAP and US rates in the 25-44 and 45-64 year age groups. AP death rates were highest for BLS and NH counties across all age groups. Rural UI death rates in the region remain unacceptably high. The reason(s) that AP death rates exceed the NAP rates is uncertain. ALS service and an available hospital were associated with lower death rates. We propose both educational and epidemiologic programs to better identify and define additional problems. PMID- 2258966 TI - Treatment of candidosis in severely injured adults with short-course, low-dose amphotericin B. AB - Thirty-three (0.7%) of 4,818 trauma patients admitted between January 1, 1987, and July 1, 1989, developed invasive candidosis requiring IV antifungal therapy. All patients were seriously traumatized. Before developing candidosis, all patients had documented bacterial infections. These infections were generally polymicrobial and were treated with multiple broad-spectrum antibiotics (an average of 5.4 antibiotics for 17.2 days). Twenty-eight (85%) of 33 patients received enteral feedings for an average of 11 days +/- 1.5 (SEM) before developing candidosis and 24 (73%) received NG/oral nystatin for an average of 7.6 days +/- 0.9 before developing candidosis. All patients with candidosis were treated with intravenous amphotericin B: cumulative dose of 157.3 mg +/- 31.3 mg given over 10 days +/- 1.1. One patient developed recurrent candidosis despite NG/oral prophylaxis and enteral feedings. Six patients (18%) died due to sepsis and multiple organ failure. The patients who died did not objectively differ from the survivors. Candidosis is an infrequent infection in severely injured patients. Candidosis was invariably preceded by treatment with multiple broad spectrum antibiotics for a variety of polymicrobial bacterial infections. NG/oral nystatin and enteral feedings did not prevent candidosis, in contrast to widely accepted beliefs. Amphotericin B therapy was safe. Recurrent candidosis was unusual. Candida infections had a high mortality rate associated with multiple blood transfusions and prolonged hospitalization. Candidosis represents a sign of severe injury and illness but can be amenable to prompt, aggressive treatment. PMID- 2258968 TI - Do trauma centers improve outcome over non-trauma centers: the evaluation of regional trauma care using discharge abstract data and patient management categories. AB - Development of regional medical care systems to treat patients who sustain major accidental injuries (trauma victims) has been based on autopsy studies which demonstrate that hospitals that meet certain accepted criteria of readiness (trauma centers) can prevent needless deaths of trauma victims. However, since only autopsy data have been available from non-trauma centers, it has not previously been possible to compare morbidity data between trauma centers and non trauma hospitals. This study examines discharge abstract data and a new patient classification system called patient management categories (PMC) which are generated from this abstract data to evaluate length of stay (LOS), complications, and death to compare morbidity and mortality data from trauma centers and non-trauma centers. Discharge abstracts for 1,332 patients with the PMC of femoral shaft fracture with operation were obtained from all hospitals in Western Pennsylvania and Maryland for 1 year. Data from trauma centers were identified and compared to non-trauma centers using the following criteria: time to OR (less than or equal to 2 days vs. greater than 2 days), age (0-12, 13-55, greater than 55 years), associated injuries, and development of complications and death. Patients treated in trauma centers had significantly fewer complications (21% vs. 33%; p less than 0.001) and lower mortality rates (p less than 0.05) than those treated in non-trauma centers. Associated injuries, age, complications, and/or delay in time to OR significantly increased intensity and length of stay in both trauma and non-trauma centers. This significantly increased the cost of care provided to these patients in both types of centers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258969 TI - Central venous oxygen saturation: a useful clinical tool in trauma patients. AB - An accurate method of estimating acute blood loss is essential in the evaluation of injured patients. Central venous oxygen (CVO2) saturation has been shown to be a sensitive and reliable correlate of blood loss in an animal model but its clinical validity is unproven. We evaluated 26 consecutive patients with an injury mechanism suggesting blood loss but who were deemed stable after initial evaluation. Vital signs (pulse, blood pressure, pulse pressure, urine output, CVP) and CVO2 saturation were serially measured. Blood loss was estimated by direct intracavitary collection or serial hematocrits and acute transfusion requirements. Despite stable vital signs, ten patients (39%) had CVO2 saturations under 65%. These patients had more serious injuries, significantly larger estimated blood losses, and required more transfusions than those patients with CVO2 saturation greater than 65%. Linear regression analysis demonstrated the superiority of CVO2 saturation to predict blood loss with a p value less than 0.005 relative to any of the normally followed parameters. CVO2 saturation is a reliable and sensitive method for detecting blood loss. It is a useful tool in the evaluation of acutely injured patients. PMID- 2258970 TI - Pediatric trauma triage: review of 1,307 cases. AB - To assess patterns of pediatric trauma triage and patient transfer to the pediatric trauma centers, the records of 1,307 patients 14 years old or less who were admitted or died during resuscitation at eight Level II Trauma Centers from January 1987 through December 1988 were reviewed retrospectively. Cases were analyzed according to the following criteria: age, diagnosis, mechanism of injury, admitting service, pediatric trauma score (PTS), length of stay in the intensive care unit (ICU) and in the hospital, and outcome. Forty-three patients were transferred to pediatric trauma centers based on local criteria. Of the remaining 1,264 patients kept at the Level II Trauma Centers, the average patient age was 8.34 year; PTS, 9.74; and length of stay, 4.46 days. Two hundred fifty eight patients (19.7%) required ICU care for an average length of stay of 2.86 days. Twenty-four patients (1.8%) died; all 24 had a PTS less than or equal to 8. In comparing the data to the guidelines in Appendix J of the American College of Surgeons' Hospital and Prehospital Resources for Optimal Trauma Care of the Injured Patient for transfer to a Level I Pediatric Trauma Center, we found that children with a PTS greater than 8 and who either require ICU care and/or have altered states of consciousness can safely be treated in the adult ICU of a Level II Trauma Center. PMID- 2258971 TI - Management issues for trauma patients with alcohol. AB - An estimated 20-25% of patients treated in emergency departments or as inpatients for trauma have been drinking and most of them have BACs of 0.10 gm/dL (22 mmol/L) or higher. Many are problem drinkers or alcoholics, smokers, and also abuse other drugs. Both acute ingestion and chronic abuse of alcohol increase the frequency and severity of injury, and may complicate patient management by mimicking head trauma, masking intra-abdominal injury, causing circulatory collapse, reducing immune response, altering hepatic metabolism, or causing delirium tremens. Proper management of a trauma patient with alcohol includes BAC determination, careful history taking for alcoholism with referral for further evaluation or treatment when indicated, and determination whether other drugs are also being misused. Failure to do these may put a physician at legal risk both for improper care of the patient and for exposing others to injury if the patient crashes after being discharged from the emergency department while still impaired by alcohol. PMID- 2258972 TI - Metabolism of platelet activating factor (PAF) and lyso-PAF in polymorphonuclear granulocytes from severely burned patients. AB - We studied the metabolism of 3H-platelet activating factor (PAF) and lyso-PAF in human polymorphonuclear granulocytes (PMN) from severely burned patients (n = 6) on days 1, 5, 9, 15, and 25 post-trauma. All patients suffered from a severe burn trauma of more than 30% total body surface area. Stimulation of PMN in healthy donors (n = 10) with the Ca-ionophore resulted in the conversion of 3H-lyso-PAF into PAF (18 +/- 2% of total radioactivity) and alkyl-acyl-glycero phosphorylcholine (alkyl-acyl-GPC, 50 +/- 6%). In burned patients a significantly reduced formation of 3H-PAF was observed between days 1 and 15 post-trauma (day 9: 1 +/- 1%, p less than 0.0001). This pattern was normalized again in patients (n = 5) who survived the trauma after septic periods and was observed during the second week post-trauma. In one patient who succumbed to his injuries a sustained inhibition of PAF formation was observed up to his death. The decreased formation of PAF correlated weakly with the appearance of immature granulocytes within the analyzed cell fraction (ratio of immature cells versus PAF-formation, r = -0.55, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258974 TI - Traumatic eyelid invagination: case reports. AB - Three rare cases of upper eyelid trauma are presented. In high-speed traffic accidents, the upper eyelids were penetrated by glass, avulsed, and then, together with pieces of glass, pushed over the globe and buried deeply in the retrobulbar area. The invaginated eyelids were pulled out gently, the conjunctiva still attached to the globes. They were repaired primarily. In these patients eyelid function and cosmesis were preserved. PMID- 2258973 TI - Conservative management of aortic lacerations due to blunt trauma. AB - Three patients with angiographically documented thoracic aortic lacerations were managed conservatively over 8 years due to the nonthreatening appearance of the injuries in two and the presence of an associated major closed head injury in a third. The lesion(s) resolved in one, diminished in another, and remained unchanged in the third. At least ten other cases managed similarly are recorded in the literature. In certain selected circumstances this approach may represent a viable alternative to the current standard of immediate surgical correction of aortic injuries. PMID- 2258975 TI - Post-traumatic intracerebral pneumatocele: case report. AB - Pneumocephalus occurs in 0.5 to 1.0% of head trauma, but may also occur after neurologic surgery, or as a result of eroding infection or neoplasm. The pathophysiology involves the presence of craniodural fistula allowing ingress of air. A ball-valve mechanism may allow air to enter but not exit the cranium, or CSF leak permits air entrance as fluid leaves the intracranial space. While a "succession splash" is considered diagnostic of pneumocephalus, most patients have nonspecific signs and symptoms such as headache. Therefore, a high index of suspicion in a patient with recent head trauma is necessary. The diagnosis is made radiographically by CT scan. This is generally performed to rule out intracranial hematoma or cerebral contusion in head trauma, but will reveal even very small quantities of air to the unsuspecting physician. Therapy is often noninvasive, allowing the craniodural defect to heal spontaneously. Selected situations require immediate operative repair of the fistula. PMID- 2258976 TI - Management of close-range shotgun injuries to the chest by diaphragmatic transposition: case reports. AB - A method of reconstructing the chest wall following close-range shotgun injuries is described. This technique requires detaching the diaphragm peripherally and suturing it above the chest wall defect, resulting in an intact chest cavity and an abdominal wall defect. This latter problem can then be addressed by a variety of standard methods. Two patients are presented with excellent long-term results of diaphragmatic transposition, which should be in the armamentarium of all surgeons who deal with trunk trauma. PMID- 2258978 TI - Carotid-esophageal fistula following a penetrating neck injury: case report. AB - Carotid arterial injuries frequently are associated with injuries to adjacent structure of the neck, particularly the esophagus and trachea. Complications from these repairs are common and fistula formation is herein described between the carotid artery and esophageal repair. PMID- 2258977 TI - Fracture-dislocation of the base of the fifth metacarpal with an ulnar motor nerve lesion: case report. AB - We report a case of delayed diagnosis of a fracture dislocation of the base of the fifth metacarpal with a resultant ulnar motor nerve lesion. The patient achieved marked improvement after fracture reduction and ulnar neurolysis. PMID- 2258979 TI - Post-traumatic priapism treated with metaraminol bitartrate: case report. AB - A 30-year-old male with post-traumatic priapism for 7 days was treated successfully by metaraminol bitartrate injection into the corpus cavernosum. This result suggests that an alpha-adrenagic agent injection into the corpus cavernosum should be considered in post-traumatic priapism at first. PMID- 2258980 TI - Traumatic left renal artery stenosis managed with splenorenal bypass: case report. AB - Splenorenal arterial bypass is a well established technique for the treatment of left renal artery occlusive disease. The following is a case report of the use of splenorenal bypass in the management of concomitant traumatic left renal artery intimal dissection and splenic laceration. Arteriographic and intraoperative findings are presented as well as a review of pertinent literature. PMID- 2258981 TI - Fractures of the coracoid process: presentation of seven cases and review of the literature. AB - Coracoid process fracture is a rare and uncommon clinical entity. Seven cases of the base of the coracoid process are presented. This fracture was isolated in one case, being in the other six cases combined with injuries, either to acromioclavicular dislocation or to fracture of the superior glenoid cavity disorder. One of these patients had associated fractures of the clavicle and the coracoid process. The treatment was conservative in all cases. Results were satisfactory and therefore nonoperative management is advocated. PMID- 2258982 TI - Septic hip in pelvic fracture with urologic trauma: case report. AB - Urologic injuries occur in 10% of pelvic fractures and hip sepsis is a rare complication. The symptoms of a septic hip are often not as dramatic when found in the setting of an acute pelvic fracture and may be overlooked. A case is presented with a review of the literature. Early recognition and aggressive surgical debridement are important to prevent the long-term sequelae of septic arthritis. PMID- 2258984 TI - Intra-aortic balloon pump for combined myocardial contusion and thoracic aortic rupture. AB - The coexistence of myocardial contusion and thoracic aortic injury is probably more common than recognized following rapid deceleration multisystem trauma. This report describes the successful application of intra-aortic balloon counterpulsation in a critically injured patient requiring emergent repair of a thoracic aortic tear complicated by ventricular failure due to cardiac contusion. PMID- 2258983 TI - Delayed, exsanguinating pelvic hemorrhage after blunt trauma without bony fracture: case report. AB - We present a case of a young man who developed a delayed, life-threatening hemorrhage after blunt pelvic trauma. He did not have a bony fracture. Successful management of the hemorrhage with angiographic embolization and the complex subsequent course are discussed. PMID- 2258985 TI - Intramyocardial shotgun pellets diagnosed on initial emergency room chest X-ray: case report. AB - The diagnosis of retained intracardiac missile is usually made at thoracotomy or fluoroscopy. Close inspection of plain chest X-rays may reveal blurring of radiopaque objects that are moving with the beating heart. In a gunshot wound victim who is initially stable, observation of this phenomenon should prompt a very high index of suspicion for cardiac injury. Invasive hemodynamic monitoring is indicated, and thoracotomy should be performed if penetrating cardiac injury is confirmed. PMID- 2258986 TI - Plain radiographic evaluation of the aorta. AB - As the main trunk of the systemic arteries, the aorta often reflects on chest radiography the status of the left ventricle centrally and the systemic circulation distally. Lesions of the aorta also affect the surrounding structures, providing telltale signs of the overall situation. Although newer imaging modalities have contributed a good deal to the evaluation of the aorta, chest radiography is still the most used baseline study. By first deriving full information from the routine chest films, one can better assess the necessity for and sequence of additional procedures. The use of digital chest radiography, which provides a clearer image of the aorta and surrounding structures, emphasizes the importance of plain-film interpretation. In this article the radiographic signs of aortic diseases in adults are presented. PMID- 2258987 TI - Conventional CT of the aorta. AB - The advent of CT has changed the way thoracic aortic aneurysms and dissections are evaluated. In many cases, CT is the only roentgenographic examination needed beyond plain radiograph. In evaluating aneurysm. CT's advantage over aortography is that it shows the wall and the mural thrombus, not just the contrast column. In some cases of aneurysm, however, particularly those arising near the aortic arch, aortography may be necessary to establish the precise location of the lesion with respect to the brachiocephalic arteries. In evaluating dissection, CT is less invasive and at least as accurate as aortography. As with aortography, the classic findings are contrast-filled multiple channels with intervening intimal flap(s). CT's particular advantage over aortography is that it permits diagnosis of dissection when blood in the false channel is clotted rather than free-flowing. In this case, the diagnosis can be made by demonstrating displaced intimal calcifications or the high-attenuation thrombus in the aortic wall or periaortic tissues. In cases of acute dissection for which emergency surgery is considered, however, aortography is preferred to CT because CT cannot provide information about aortic insufficiency or the condition of critical arterial branches such as the coronary, brachiocephalic, mesenteric, and renal arteries. In follow-up of treated aortic dissection CT is preferred over aortography because it is noninvasive and more informative. Compared with MRI, CT has the advantages of greater reliability and of compatibility with life-support apparatus. MRI is not able to depict calcification, so any displacement of calcification cannot be detected. MRI is most suitable for follow-up of treated patients or for acute patients who are stable or who cannot tolerate intravenous contrast agents. A flexible approach is essential in choosing the appropriate radiographic tests in the work-up of aortic dissection. In this article, a workable strategy is outlined, but the radiologist should not hesitate to change the order of tests or use a second test if results from one test are confusing or inconsistent with other clinical data. PMID- 2258988 TI - Ultrafast computed tomography in the diagnosis of aortic aneurysms and dissections. AB - UFCT, by virtue of its 50 to 400 millisecond acquisition times, 0.75 to 1.5 mm resolution, and excellent vascular opacification, provides a rapid, minimally invasive method for assessing aortic aneurysms and dissections. During a 3.5-year period, 50 patients with suspected thoracic, thoracoabdominal, and abdominal aortic aneurysms or dissections were evaluated using the Imatron C-100 UFCT scanner. Eighteen patients had thoracic or thoracoabdominal aneurysms. 17 had thoracic or thoracoabdominal dissections, 7 had abdominal aneurysms, and in 8 no aneurysms or dissections were found. In 23 of the 35 patients with thoracic or thoracoabdominal aneurysms or dissections, the UFCT findings accurately reflected the findings at aortography, surgery, or autopsy. There was one false-positive examination. The remaining 11 patients with UFCT findings of aneurysm or dissection were followed clinically. In the 7 patients with abdominal aneurysms, 4 were confirmed by angiography or surgery, and 3 were followed clinically. Of the 8 patients with negative UFCT examinations, 2 had subsequent angiography that failed to show an aneurysm, and 6 were followed from 6 to 30 months without developing findings suggestive of aneurysm. UFCT appears to be a useful, minimally invasive technique for detecting and following aortic aneurysms and dissections. PMID- 2258989 TI - Transesophageal echocardiography in the assessment of aortic pathology. AB - Transesophageal echocardiography is an excellent method for diagnosing aortic pathology, especially dissection, and has replaced transthoracic echocardiography for this purpose. Advantages of the transesophageal method are its speed, portability, and accuracy. Disadvantages are the requirements of operator skill and patient sedation, as well as poor visualization of the distal 2-3 cm of the ascending aorta. Transesophageal echocardiography may become the initial diagnostic procedure of choice when acute dissection is suspected. PMID- 2258990 TI - Current role of conventional and digital aortography in the diagnosis of aortic disease. AB - The availability of the less invasive techniques such as CT, MRI, and digital angiography require reexamination of the indications for conventional screen-film aortography. Because of poor image quality, IV digital subtraction angiography should be limited to congenital aortic disease and follow-up cases. Intraarterial digital angiography can be used as a supplement to or as a replacement for conventional aortography in most cases. Care should be used in substituting intraarterial digital angiography for conventional studies in aortic dissection and aortic rupture; continuing problems with digital subtraction artifacts may introduce error in cases with subtle abnormalities. In aortic aneurysm, CT is usually sufficient for diagnosis and surgical planning with angiography used for inconclusive examinations or more accurate determination of branch involvement. CT is the primary diagnostic examination in suspected chronic or subacute dissection and is the method of choice in sequential studies of patients following medical or surgical therapy for dissection. In acute aortic dissection, either angiography or CT may be used and are equally diagnostic. Angiography is most helpful in aortic dissection with suspected brachiocephalic vessel involvement, coexistant coronary artery disease, or in cases of indeterminate CT. In blunt chest trauma, aortography remains the examination of choice in the diagnosis of aortic transection. CT may play a role in excluding aortic damage in stable patients with a low clinical suspicion of aortic transection. PMID- 2258991 TI - Bronchial artery embolization therapy. AB - Bronchial artery embolization, which was first described in 1973, has now become an accepted method of therapy for massive hemoptysis. Successful use of this technique requires a knowledge of the bronchial anatomy, an understanding of the patient population for whom this technique is best suited, a familiarity with the technical aspects of the procedure, and an awareness of the complications associated with this technique. Angiographic evaluation and bronchial artery embolization may be used to stabilize the patient prior to surgical therapy or may represent definitive therapy. PMID- 2258992 TI - Sonographic and Doppler features of infantile hepatic hemangiomas with pathologic correlation. AB - The sonograms of five patients with a diagnosis of infantile hepatic hemangioma were retrospectively reviewed to analyze their sonographic and Doppler characteristics. Three patients had single lesions, whereas two had multifocal involvement. All lesions except one were hypoechoic, well-circumscribed, and solid; the exception was hyperechoic. Findings of high flow, ie, large draining veins, an abrupt change in aortic caliber, and the presence of Doppler signal throughout the lesion were seen in three of five patients. The sonographic findings correlate well with the pathologic findings of multiple vascular channels separated by fibrous septa. The major differential diagnosis of infantile hepatic hemangioma includes hepatoblastoma and metastatic neuroblastoma. Although some of their sonographic features may simulate a hemangioma, large draining veins and changes in aortic caliber are not reportedly seen. Doppler flow was not seen in either of these malignant neoplasms in our study and, to date, has only been reported peripheral to three cases of hepatoblastoma and not at all in metastatic neuroblastoma. We propose an algorithmic approach dependent upon the sonographic-Doppler appearance. PMID- 2258993 TI - Pulsed Doppler on a vaginal probe. PMID- 2258994 TI - Diagnosis of early embryonic demise by endovaginal sonography. AB - To determine the embryonic size at which cardiac activity is always seen in a normal early pregnancy, 398 endovaginal sonograms were evaluated in which the gestational sac contained a yolk sac and/or embryo of less than or equal to 12 mm in crown-rump length (CRL). In the 99 sonograms in which there was a yolk sac but no identifiable embryo, cardiac activity was absent in 75; 58 of these pregnancies progressed normally. Of the 299 sonograms where there was an identifiable embryo with CRL less than or equal to 12 mm, cardiac activity was absent in 31; 29 of these were proven to be failed pregnancies. In two cases the pregnancy progressed normally; the CRL was 2 mm in one case and 4 mm in the other. We conclude that once an embryo is seen by endovaginal sonography, the absence of cardiac activity usually indicates embryonic demise. However, when cardiac activity is absent, one should refrain from definitively diagnosing embryonic demise, based on a single sonogram, if the CRL is less than 5 mm. PMID- 2258995 TI - Transvaginal sonography of postmenopausal ovaries with pathologic correlation. AB - The sonographic appearance of 67 ovaries in 34 postmenopausal women who underwent preoperative transvaginal sonography (TVS) was correlated to findings on pathologic examination. Both ovaries were detected by TVS in 60% of the women examined; in 85%, at least one ovary was detected. The size of the normal, sonographically visualized postmenopausal ovary was 2.2 +/- 0.7 cm in transverse, 1.2 +/- 0.3 cm in anteroposterior, and 1.1 +/- 0.6 cm in longitudinal axes, with an average volume of 2.6 +/- 2.0 cm3. The average size of ovaries that were not detected by TVS was 0.7 x 0.4 cm (range, 0.3 to 1.3 cm); most of these (five of six) were atrophic on pathologic exam. The difference between actual and sonographically measured size was negligible (TVS overestimated by 0.3 cm). Four simple cysts that ranged from 0.5 to 3.5 cm were found by TVS and confirmed pathologically, as were three benign serous cystadenomas that ranged from 2.5 to 3.5 cm, one 3 x 6-cm tubal carcinoma, and one 1 X 4-cm paratubal cyst. TVS missed a 6-cm dermoid, a 2.5-cm cystadenoma, a 0.8-cm Sertoli cell tumor, and a 0.5-cm fibrothecoma that were nonpalpable but that were found on pathologic examination. None of the missed lesions were palpable preoperatively. The positive predictive value was 94% for detection of an ovarian mass; the negative predictive value for exclusion of an ovarian lesion was 92%. It is concluded that TVS can accurately delineate the ovaries in most, but not all, postmenopausal women and that only rarely will pathologic lesions not be detected by TVS. PMID- 2258996 TI - Endoscopic ultrasonography in the diagnosis of depth invasion and lymph node metastasis of carcinoma of the papilla of Vater. AB - To evaluate diagnostic accuracy of endoscopic ultrasonography (EUS) on the extent of carcinoma of the papilla of Vater, 28 patients were preoperatively evaluated using our EUS grading system. EUS was accurate in diagnosing carcinoma infiltration into the duodenal proper muscle layer (100%) and into the pancreas (75%). When compared with postoperative histologic findings, the overall accuracy of EUS in assessing local infiltration was 89.3%. Misdiagnoses occurred in three cases due to microinfiltration of the carcinoma. Lymph node metastasis around the pancreatic head was accurately diagnosed in nine cases; however, mesenteric lymph node metastasis could not be detected in four cases because the tumor was far from the scanning site. PMID- 2258997 TI - Prenatal diagnoses in unilateral empty renal fossa. AB - Six cases of unilateral empty renal fossa diagnosed by obstetric sonography are described. The anomalies reported (ectopic kidney, cross-fused ectopic kidney, and unilateral renal agenesis) have not yet been described in the prenatal literature, to our knowledge, in fetuses that are otherwise normal. The study also demonstrates that, in spite of their nonvital in utero role, single kidneys may show compensatory hypertrophy. PMID- 2258998 TI - Umbilical artery Doppler velocimetry in pregnancies of less than 21 weeks' duration. AB - Most Doppler ultrasound investigations of the umbilical artery circulation have been confined to beyond 16 weeks' gestation. The purpose of this study is to explore the evolution of this circulation in human pregnancies of less than 21 weeks' gestation. We studied 169 low-risk pregnant women (125 longitudinally and 44 cross-sectionally) with a pulsed Doppler system on 357 separate occasions between 9 and 20 weeks of gestation. Systolic/diastolic (S/D) ratios were used for waveform analysis. We obtained umbilical waveforms as early as 9 weeks. Before 13 weeks, all fetuses had absent end-diastolic velocity (AEDV), then progressive development of end-diastolic velocity (EDV) appeared from 13 to 18 weeks. At 18 weeks, all fetuses had developed EDV. S/D ratios progressively declined from 13 to 20 weeks (y = 17.67 - 1.26x + 0.3x2; r2 = .95). A cross sectional evaluation of fetal heart rate in 136 fetuses revealed a significant negative second-order polynomial relationship with gestational age between 9 and 20 weeks y = 245.84 - 10.33x + 0.27x2; r2 = .93). In 136 fetuses, 185 measurements of S/D ratios and their corresponding fetal heart rate revealed no relationship (weighted linear regression, r2 = .005). Mean fetal heart rate was significantly higher when EDV was absent (164.6 +/- 10.8 standard deviation [SD], n = 74) than when EDV was present (150.1 +/- 5.8 SD; n = 62; P = .000). Thus, upstream factors may be of little importance in the generation of umbilical artery velocity waveforms in early pregnancy. Umbilical Doppler velocimetry in the first half of pregnancy gives a functional assessment of the vascular development of the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2258999 TI - Endovaginal sonographic appearance of a DES uterus. PMID- 2259000 TI - Uterine myolipoma. Magnetic resonance imaging, computed tomographic, and ultrasound appearance. PMID- 2259001 TI - Anorectal atresia presenting as an abdominopelvic mass. PMID- 2259002 TI - Sonographic detection of necrotizing enterocolitis in infancy. PMID- 2259003 TI - [The partial characterization of neutrophils and lymphocytes chemotactic factors from murine anagenic hair bulb extract]. AB - The murine anagenic ++ hair bulb extract (HBE) showed a chemotactic activity for both neutrophils and lymphocytes in vitro. The activity for both cells was retained after heating at 56 degrees C for 30 min, and dialysis. However, heating at 100 degrees C for 10 min inactivated the chemotactic activity for neutrophils, but not for lymphocytes. Activity for neutrophils was sensitive to degradation by trypsin or pronase but stable to neuraminidase treatment. On the other hand, activity for lymphocytes was not affected by protease treatment, but was reduced by approximately 30% after being treated by neuraminidase. These findings suggest that HBE contains at least two kinds of chemoattractants for neutrophils and lymphocytes. PMID- 2259004 TI - [Apolipoprotein E phenotypes and psoriasis]. AB - Using gel isoelectric focusing method, we determine the frequencies of apoE isoform and gene of 32 patiens with psoriasis vulgaris. The patients showed higher frequencies of E3/3 and the allele epsilon 2 and lower frequencies of E3/3 and the allele epsilon 3 than the healthy Japanese control. The tendency to have higher frequencies of E3/2 and epsilon 2 was more apparent in the patients of early onset than of late onset, with severe type than with mild or moderate type, and of universal form of plaque type eruption and guttate form than of localized form of plaque type eruption. These differences fell short of statistical significance. These findings suggest us an important role of apoE2 (allele epsilon 2) over the onset and the clinical severity of psoriasis vulgaris. PMID- 2259005 TI - [The role of bacteria on facial rosacea-like dermatitis in adult type atopic dermatitis]. AB - To investigate the role of bacteria on facial rosacea-like dermatitis lesion in adult type atopic dermatitis, we measured the numbers of bacteria on the skin, nasal and pharyngeal surface of each individual, and then examined its sensitivity to antibiotics. The numbers of bacteria on the surface of skin increased according to the severity of skin eruption. Staphylococcus aureus was detected from the skin and nasal surface more than pharyngeal surface. Bacteria on the pharyngeal surface were both staphylococcus aureus and haemophilus parainfluenzae. Therefore, it is suggested that bacterial flora on the pharynx is different from those of the skin and nose. The treatment with antibiotics was effective for exudative lesions, whereas lichenified lesion did not respond to antibiotic therapy. These results suggest that bacteria on the skin surface are one of precipitating factors of the rosacea-like dermatitis of atopic dermatitis. PMID- 2259006 TI - [Angiolymphoid hyperplasia with eosinophilia--report of a case with reference to the vascular changes and cell infiltrates in this disease]. AB - We reported angiolymphoid hyperplasia with eosinophilia (ALHE) in a 47-year-old woman. The most characteristic histological findings were epithelioid endothelial cells with intracytoplasmic vacuoles, and remarkable arterio-venous (A-V) shunts. Mast cells, seen in the lesions, had no special relationship with eosinophils in their distribution. Degranulation of mast cells was not seen. Electron microscopic study revealed abundant cytoplasmic organellae and fine filaments in epithelioid endothelial cells. Immunohistochemical study revealed mixed infiltration of T and B lymphocytes, and polymorphous T-cell population in the lesions. These findings suggest that active vascular proliferations take place in the lesions of ALHE, that the eosinophilic infiltrate and mast cells may be independent of each other, and that the lymphocytic infiltrate probably is a reactive process. The vascular changes seen in Kimura's disease are characterized by a proliferation of capillaries with swollen, but not epithelioid, endothelial cells and vessels with lamellated adventitia. A-V shunts are not observed in its lesions. Therefore ALHE and Kimura's disease should be considered different entities. PMID- 2259007 TI - [A case of xeroderma pigmentosum treated by oral etretinate]. AB - A case of xeroderma pigmentosum (XP) with neurological disorders is reported. The patient is a 16 year old male who presented a marked photosensitivity from his early infancy. The family history is negative for XP with no consanguinity being observed. He displayed neurological symptoms such as a low IQ and audiological disturbances. He developed six basal cell epitheliomas (BECEs) on his face at age of 14. We tried oral etretinate for 4 years at a initial dosage of 30 mg per day for the possible prevention of new skin cancers. Efficacy of the drug for prevention of cancers has not been confirmed, but evidence is obtained that the drug might prevent the growth of tumors. We also reviewed the chemoprevention of skin cancers with retinoids, in patients with xeroderma pigmentosum. PMID- 2259009 TI - Proceedings of the 23rd annual meeting of the Japan Epilepsy Society and the Japanese Branch of the International League against Epilepsy. October 6-7, 1989, Tokyo. PMID- 2259008 TI - [Organ culture of skins from patients with benign familial chronic pemphigus]. AB - Skin explants from 2 lesional skins and 3 normal appearing skins of patients with benign familial chronic pemphigus (BFCP) were organ cultured with and without various reagents. In the culture of involved skin, acantholysis which was also observed prior to culturing and which strengthened during the 72 hr culture, was not suppressed when betamethasone or retinol acetate was added to the medium. In the culture of un-involved skin explants with medium only, acantholysis was induced 24-48 hr after initiation of culture, and became apparent after 72 hr. Such experimentally induced acantholysis was almost completely suppressed by the addition of betamethasone, but not the addition of retinol acetate. These findings suggest that steroid has the efficacy to reduce blistering in BFCP, and that this in vitro model is useful for clarifying the pathogenesis as well as for discovering new drugs for the treatment of this disease. PMID- 2259010 TI - Magnetoencephalography and epilepsy research. AB - The theory of magnetoencephalography (MEG) and its application to epilepsy research are reviewed briefly. The MEG prediction appears to agree in general with regions where epileptiform discharges are found on the electrocorticogram. MEG appears to have a somewhat better localizing capability than EEG, although MEG may well miss the tangential component of magnetic fields. Thus, the combination of MEG and EEG may be more fruitful than either one alone. PMID- 2259011 TI - Surgical treatment of epilepsy in the comprehensive care program: advantages and considerations. AB - To properly establish the surgical treatment of epilepsy in the comprehensive care program, we planned a surgical strategy mainly for a temporal lobe epilepsy and have performed 60 temporal lobectomies. The surgical candidates were selected from 142 patients who met the initial criteria, and passed the initial evaluation for surgical intervention. Forty-five patients had long-term intracranial EEG recording, and circumscribed organic lesions were disclosed in 27 patients by neuroimaging techniques. The outcome of 23 patients who were followed for 2 years postoperatively was complete freedom from complex partial seizures in 17 patients (74%) and an increase in full employment from 2 to 10 patients. Despite the possible surgical complications, including detrimental effects on the higher cerebral functions, it is essential that the surgical treatment of epilepsy should be established as a part of the comprehensive care program. Our experiences and analyses of the state of the art in surgical intervention also suggest that surgical indications for more intractable patients whose social adjustment is less hopeful should be established and the surgical care system for these patients should also be planned. Furthermore, some patients may be free from recurrent seizures postoperatively, but still have difficulties in social rehabilitation. The problems for such patients remain unsolved. PMID- 2259012 TI - Deteriorating epilepsies: severely deteriorated cases. AB - A total of 28 cases of severely deteriorated epileptic patients were seen at out- and inpatient services in the past 12 years. In 22 out of these 28 cases, the etiology for the deterioration was considered to be due to either repetitive intractable seizures or antiepileptic drugs (AEDs) or both. Although differential diagnoses were difficult in many cases as to the responsible causes, namely seizure vs. AEDs, it was considered in 6 cases that AEDs took a major role in their deterioration. Details of such cases are presented. Special emphasis was made to the fact in which they frequently showed episodes of acute or ataxia and confusion often associated with febrile illness. They took a course of acute or subacute exacerbation and partial remission. Discussion was held on the nature and possible avoidance of these deteriorations. PMID- 2259013 TI - Presurgical evaluation of epileptic patients with subdural recording and functional mapping. AB - The indications and applications of brain functional mapping with subdurally implanted electrodes are reviewed briefly. The mapping can be performed outside the operating room and is useful for presurgical study of patients who have a complex distribution of epileptiform discharges and for minimizing functional deficits postoperatively. The major disadvantages of the procedure are the inflexibility of the electrode positions and the necessity of a craniotomy to insert and remove the subdural electrodes. PMID- 2259014 TI - An ontogenic study on the mechanism of the initiation of seizure activity in rats. PMID- 2259015 TI - Two types of EEG spikes in the kindled rabbit hippocampus. AB - The characteristics of interictal EEG spikes were studied in the rabbit hippocampus. After kindling for 2-4 weeks, rabbits were anesthetized and curarized for acute experiments. There were two types of EEG spikes in the kindled hippocampus; one (B) had its source in the stimulated side, and the other (A) in the contralateral side. In addition, compound EEG spikes (C) were observed that consisted basically of B and A spikes. Intracellular counterparts of A and B spikes were generally a depolarization-hyperpolarization sequence in the CA1 pyramidal cells. On the other hand, counterparts of the C spikes were initial depolarization with a superposed spike burst followed by relatively shorter lasting hyperpolarization which seemed to indicate an enhancement of excitation during the kindling process. PMID- 2259016 TI - Stimulus train-induced bursting in hippocampal slices: difference between CA1 and CA2/3 subfields. AB - We studied the relationship between CA2/3 and CA1 subfields in the generation of stimulus train-induced bursting using in vitro hippocampal slices. Repeated stimulation to the stratum radiatum induced three types of epileptiform activities: afterdischarge bursts, spontaneous bursts and single stimulus triggered bursts. In the intact slices, spontaneous bursts in CA3 preceded those in CA1, whereas afterdischarge bursts in CA3 followed those in CA1 when it was possible to distinguish differences in the burst onset. After transection between CA2/3 and CA1, neither spontaneous nor triggered bursts could be induced or maintained in isolated CA1, where only small afterdischarge bursts with a higher bursting frequency were observed. It was difficult to induce afterdischarge bursts by the tetani to the mossy fibers. Some of the mechanisms underlying the generation of these stimulus train-induced bursts are discussed. PMID- 2259017 TI - Seizure generation mechanisms in reflex epilepsy. AB - To know the seizure generation mechanisms in reflex epilepsy, we performed red flicker and flickering geometric pattern stimulations for photosensitive epilepsy, and neuropsychological EEG activation for graphogenic epilepsy. These activations were effective to provoke seizure discharges. The EEG discharges of absence seizure in photosensitive epilepsy started mainly from the posterior regions, which became evident by the reduction of stimulus intensity. Mental activity performed with the hands provoked the central-dominant discharges with unilateral myoclonic seizure as well as generalized discharges with bilateral myoclonic seizure in graphogenic epilepsy. These findings suggest that the initiation of these seizures may relate to the hyperexcitability of the focal cortical areas, which correspond to those activated by the special EEG activation. PMID- 2259018 TI - Onset and propagation of hippocampal seizures in man. PMID- 2259019 TI - Subtypes of temporal lobe epilepsies: a clinical point of view. AB - We studied 40 patients with temporal lobe epilepsies who had long-term intracranial EEG recordings and temporal lobectomies. They were divided into 3 groups on the basis of the anatomical site of seizure origin. An electrode implantation technique combined intracerebral depth electrodes with subdural strip electrodes. The seizures were of amygdalo-hippocampal origin in 18 patients, lateral temporal in 13 patients, and temporo-basal in 9 patients. The clinical and EEG features were reviewed retrospectively with regard to 3 factors in each patient: localization of interictal spikes in the scalp-recorded EEG, signal symptoms (auras), and presumed etiologies. Epilepsy with amygdalo hippocampal and lateral temporal seizures was found to be distinguishable by the electroclinical features. It seems practical to classify these 2 subtypes of temporal lobe epilepsies as in the 1989 Classification of Epilepsies and Epileptic Syndromes. Temporal lobe epilepsies thus defined can be regarded as epileptic syndromes rather than a cluster of seizure manifestations. PMID- 2259020 TI - Special etiologies in the classification of epilepsy--with special reference to brain malformations. AB - I analyzed 18 cases of brain malformations detected by autopsy and five cases of lissencephaly diagnosed by CT scan or MRI. 1) Autopsy Cases Brain malformations were highly complicated, and many cases showed more than one type of brain malformation. Epileptic seizures were observed in 13 of 18 cases. In most cases, the seizures were characterized by infantile onset, a high incidence of tonic seizures and difficulties in controlling them. 2) Patients with Lissencephaly They all had severely retarded psychomotor development. Tonic seizures were observed in all the five patients, two of whom had a past history of infantile spasms. The EEG patterns of these patients were varied. It is thought that a relationship exists between the severity of CT or MRI findings and that of EEG findings. PMID- 2259021 TI - Mexiletine add-on therapy for treatment of intractable epilepsy. PMID- 2259022 TI - Prophylactic effects of acetaminophen suppository on febrile convulsions: an epidemiologic and twin study. PMID- 2259023 TI - Clinical and EEG studies on complex partial seizure in children. AB - In 18 (40%) of 45 patients with CPS, paroxysmal discharges were hard to be found on their interictal EEG examinations. These patients were, however, not different from the other 27 patients with paroxysmal discharges on EEG as for the onset, prognosis for attack, complication of generalized tonic-clonic seizure and febrile convulsion, family history and adaptation to society. PMID- 2259024 TI - A case of chronic mumps virus encephalitis manifesting intractable epileptic seizures. PMID- 2259025 TI - Intracranial EEG changes during intracarotid sodium amobarbital (WADA) test in epileptic patients. PMID- 2259026 TI - The determination of motor cortex in epilepsy surgery: identification of motor cortex under general anesthesia. PMID- 2259027 TI - Arteriovenous malformations and epilepsy--natural history and surgical results with associated seizure. PMID- 2259028 TI - The determination of language areas by electrical stimulation: application to epilepsy surgery. PMID- 2259029 TI - Antiepileptics and bone atrophy--3-year follow-up study. PMID- 2259030 TI - Studies on pharmacoepidemiology of antiepileptic adverse reactions. PMID- 2259031 TI - Five epileptic cases who manifested psychotic states under the toxic levels of antiepileptic drugs. PMID- 2259032 TI - Effects of superoxide dismutase on limbic status epilepticus in rats. PMID- 2259033 TI - Eating epilepsy. PMID- 2259034 TI - Magnetic resonance imaging in epileptic patients with intractable complex partial seizures. PMID- 2259035 TI - Changes in regional cerebral blood flow in patients with temporal lobe epilepsy- retrograde analysis by comparison with depth EEG recordings. PMID- 2259036 TI - Feasibility of subclassification of temporal lobe epilepsy (1989): an etiological overview. AB - Temporal lobe epilepsy with amygdalohippocampal seizures may have episodes of severe convulsions in childhood more frequently and the onset age is significantly lower compared to epilepsy with lateral temporal seizures. To the contrary, tumorous lesions are found more frequently in epilepsy with lateral temporal seizures. In view of the presumed known etiologies in relation to the localization of epileptogenic foci, the Classification of Epileptic Syndrome (1989), subdividing temporal lobe epilepsies into 2 groups, was found to be useful. PMID- 2259037 TI - IgG subclasses in epileptic children. PMID- 2259038 TI - Seizure elicited by VPL stimulation in cobalt induced epilepsy model. PMID- 2259039 TI - Effect of complete section of corpus callosum and massa intermedia on feline penicillin-induced thalamic focus. AB - ECoG and depth EEG changes before and after the complete section of CC and MI were investigated in the Pc-induced thalamic focus model. The results suggested that the mesencephalic reticular formation might be necessary for the generalization and maintenance of ictal discharges from the thalamic focus in cats. PMID- 2259040 TI - Methionine enkephalin in the brain of El mouse: HPLC/RIA analysis. PMID- 2259041 TI - Serum melatonin kinetics in epileptic children with or without photosensitivity. PMID- 2259042 TI - The effect of unilateral claustral lesion on intermittent light stimulation induced seizure in D, L-allylglycine treated cats. PMID- 2259043 TI - Distribution of GABA concentrations and GAD activities in the parietal cortex and the hippocampal CA1 in an El mouse. PMID- 2259045 TI - Hippocampal kindling in congenitally acallosal mice (the first report). PMID- 2259044 TI - The changes in guanidino compounds in the brain of amygdala kindled seizure- comparisons with electric convulsive shock seizure. PMID- 2259047 TI - Proceedings of the seventh meeting of the Japanese Association for Adolescent Psychiatry. November 25, 1989, Nagoya. PMID- 2259046 TI - Metabolic maps of amygdala kindling. PMID- 2259048 TI - [The effects of a recipient's openness and conveyance to a third party of the self-disclosure on changes in the discloser's liking and self-disclosure]. AB - One hundred and ninety-nine university students (101 males, 98 females) served in a study designed to examine various factors affecting a discloser's degree of liking of and self-disclosure to a recipient. Specifically, the effects of (1) the recipient's degree of openness (high, low), (2) whether or not the recipient conveyed the discloser's self-disclosure to a third party (yes, no), and (3) the intimacy of self-disclosure by the discloser (high, low) were assessed in terms of (a) change in self-disclosure by the discloser and (b) change in liking by the discloser. Results confirmed the hypotheses that: (1) the degree of openness of the recipient and the conveyance of self-disclosure by the recipient would interact with change in the discloser's liking of and self-disclosure to the recipient, and, (2) the degree of openness of the recipient and the intimacy of self-disclosure would interact with change in the discloser's liking of and self disclosure to the recipient. Moreover, females were found to be more sensitive than males to conveyance by the recipient. PMID- 2259050 TI - [The effect of eye contact and verbal content about impression on affective reactions of the other partner]. AB - The present experiment was conducted to examine the hypothesis that extended eye contact might intensify direct relations in a social encounter with another individual. Organized into same sex dyadic pairs, 64 students (32 male, 32 female) were divided into two groups (high- and low-eye contact) and assigned to either a positive or negative condition defined in terms of the verbal content of the confederate. With respect to the affective components of these dyadic interactions, it was found that under the positive evaluation condition, greater liking occurred in the high-eye contact group. In contrast, greater liking occurred in the low-eye contact group under the negative evaluation condition. Similar patterns were found with respect to the evaluation of "sincerity", "interest" and "attraction" toward the confederate. All these findings were in accordance with the hypothesis stated above. However, findings related to the qualification factor of the interaction as indexed by "skill of address", "attentiveness" and "confidence" were not in accordance with expectations. It was concluded, therefore, that increasing eye contact selectively intensifies the affective elements in a dyadic relationship while leaving the qualification aspects unaffected. PMID- 2259049 TI - [A Japanese version of the Type A questionnaire (MYTH) for children]. AB - The reliability and validity of a Japanese version of the Matthews Youth Test for Health (MYTH) are reported. The MYTH is a questionnaire by which the degrees of Type A in children are measured. In Study 1, 23 teachers in kindergartens and day nurseries rated their children (N = 482 in all; 3 to 5 years old) by using the MYTH. Statistical analyses of the data indicate that this questionnaire is reliable and internally consistent, and has two factors, competitiveness and impatience-aggression, just as the American version. In Study 2, children (4 to 5 years old) were divided into two groups, Type-A (N = 24) and Type-B (N = 25), according to the scores of the MYTH. Each child was given three tasks (mailing, discrimination, and putting-in-chips). The results show that in those tasks Type A children show more time urgency, hard-driving, and competition than Type-B children, which suggests that the Japanese version has a high construct validity. These two studies indicate that the Japanese version can be used in Japan to study Type A of young children. PMID- 2259051 TI - [Trends in studies of prosocial behavior]. AB - The present article provides an analysis of past trends and recent developments in studies of prosocial behavior which began in the latter half of the 1960s. Particular emphasis is placed on studies relating to the subsequent bystander effect, the development of decision-making models incorporating interactions of various factors, empathy, perspective-taking, and prosocial moral judgment as an important mediating factor in motivation, including the viewpoint of self perception. The article concludes by considering the relevance of studies of prosocial behavior to psychology at large and the directions such studies might take in the future. PMID- 2259052 TI - [Patient's delay and doctor's delay in the primary treatment cases of pulmonary tuberculosis detected by subjective symptoms]. AB - Delays in case finding were studied for the primary tuberculosis patients who were discharged from our hospital in 1987. Of 321 tuberculosis patients who were released from our hospital in 1987, 171 patients received primary treatment. Eighty one of them had been detected by their symptomatic visits. Patient's and doctor's delays tended to be longer in the cases of males than of females. For both males and females patient's delay tended to be longer in younger age group. Total delay until definite diagnosis by 50% and 80% of all diagnosed were 1.6 months, and 3.5 months respectively. Patients with total delay of more than three months were younger in age and were hospitalized longer than patients with total delay of less than 3 months. All cases with total delay of more than three months were smear positive. PMID- 2259053 TI - [Study on postoperative perforation in patients with chronic empyema--reoperated cases]. AB - In 18 cases undergone reoperation because of perforation after the initial operation for primary and secondary chronic empyema during the period from 1974 through August 1986, we evaluated findings of fistula, procedures and causes of failure of the initial operation, and procedures and results of reoperation. Subjects consisted of 16 cases of chronic empyema complicated with pulmonary tuberculosis, 1 case of group III nontuberculous mycobacteriosis, and 1 case of chronic empyema secondary to pulmonary fibrosis. All patients had fistula at the initial operation. The initial operation was performed by Kinchu method in 8 cases, pulmonary detachment in 6 cases, and thoracic cavity reduction chiefly by a modification of Grow's method in 4 cases. The initial operation failed because of incomplete closure of the fistula in 11 cases (61%) and appearance of new fistula in 7 cases (39%). In reoperation, the fistula was closed by pedicle muscle plombage in 1 case undergone the initial operation by Kinchu method, while thoracic cavity reduction chiefly by a modification of Grow's method in all of the other 17 cases. After the operation, 15 patients (83%) were cured, 16 patients (89%) could be socially rehabilitated and 2 patients (11%) had recurrence of empyema. Two recurrent patients died from hepatitis and exacerbation of nontuberculous mycobacteriosis, respectively. Out of 10 patients undergone pedicle muscle plombage, 8 patients (80%) were cured. From these findings, we consider that the results of one stage operation can be improved by applying pedicle muscle plombage for closure of fistula after the initial operation following treatment with effective antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259054 TI - [Studies on the changes in clinical features of tuberculosis]. AB - The epidemiological and clinical features of tuberculosis have largely changed in recent years owing to rapid improvement of social environments and therapeutics. For the determination of these changes, especially clinical ones, the author made comparative studies on all patients hospitalized in National Sanatorium Higashi Saitama Hospital during the periods from 1964 to 1966 and from 1985 to 1988. The 1964-66 group included 400 patients and the 1985-88 group included 508, making a total of 908. The results are as follows: 1. Primary treatment cases with positive bacteriology, atypical mycobacteriosis cases and those with complications increased in number, while re-treatment cases decreased. 2. Comparison was made for bacteriologically positive primary treatment cases between the two groups, namely 112 patients of 1964-66 group and 213 patients of 1985-88 group. The results were: (1) 1985-88 group included larger number of more aged patients and patients with complications. (2) The two groups showed no marked differences in radiological findings such as the size of affected areas or cavities and the rate of cavitation. The patients with radiologically fibrocaseous findings increased in number. (3) The incidence of lower lung field tuberculosis was almost doubled in the 1985-88 group, and this type of tuberculosis was more frequently observed among patients below 29 and over 70 years of age and among those complicated with diabetes mellitus. In chest CT, eight out of 10 patients with lower lung field tuberculosis showed some changes in their mediastinum and/or hilar lymph nodes. This may suggest that the primary mediastinum and/or hilar lymph nodes tuberculosis had perforated into the trachea or bronchi. (4) Although the two groups did not show difference in mortality, deaths due to complications were observed more in the 1985-88 group. However, 4 patients in this group died of tuberculosis itself, all within about 40 days after hospitalization. PMID- 2259055 TI - [A case of miliary tuberculosis associated with acute respiratory failure during pregnancy]. AB - A case of miliary tuberculosis associated with acute respiratory failure during pregnancy was reported. A 39-year-old, 29-week pregnant woman was admitted to our hospital with complaints of nonproductive cough and fever on June 12. On admission, her temperature was 38.2 degrees C; pulse rate was 90/min., and blood pressure was 120/76 mmHg. Physical examination revealed moist rales at right lung basis. Chest X-ray showed small nodular infiltrates in right lower lung field. Laboratory data revealed positive CRP, accelerated ESR and increased level of alpha 2-globulin. The number of T-cells was markedly decreased (14/mm3). The PPD skin test was negative, and the sputum smears for acid-fast bacilli were negative. Suspected of bacterial or viral pneumonia, the patient was treated with antibiotics (CPM, EM and CAZ), which had no effects for her. On June 16, the Chest X-ray showed infiltrates throughout bilateral lung fields, and the patient became increasingly dyspneic. On June 18, the results of arterial blood gas, analysis under room air were: PaO2 26.7 Torr, PaCO2 29.0 Torr, pH 7.505. Because of severe hypoxemia, she was intubated and placed on a volume-cycled respirator. Hydrocortisone (1000 mg, daily) was added to treatment because ARDS was suspected. Since the smears of tracheobronchial secretions showed acid-fast bacilli on June 24, she was diagnosed to have miliary tuberculosis. Then the intensive therapy with antituberculosis drugs (isoniazid 400 mg, rifampicin 450 mg, and streptomycin 1g, daily) was started. The non specific antibiotics were discontinued; hydrocortisone was tapered and stopped. The next week, she became afebrile and hypoxemia steadily improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259056 TI - [Clinical characteristics of the lung diseases due to Mycobacterium avium and Mycobacterium intracellulare classified by DNA probe test]. AB - Clinical characteristics of the lung diseases due to M. avium and M. intracellulare classified by DNA probe test were investigated. Between M. avium and M. intracellulare, there was no significant differences in the samples' backgrounds and the clinical characteristics except for their prognoses. The prognosis of the lung diseases due to M. intracellulare was better than those due to M. avium, and M. avium was revealed to be highly susceptible to Cyclocerine than M. intracellulare. No remarkable difference was found in the susceptibility to other antituberculous drugs. PMID- 2259057 TI - [Advance in diagnostic methods for mycobacteria]. PMID- 2259058 TI - [Tuberculosis in high risk groups]. PMID- 2259059 TI - [Late ventricular potentials and spontaneous and electric stimulation-induced ventricular tachycardia]. AB - The purpose of this study was to compare the relation of signal averaged variables of the QRS complex to spontaneous and to inducible sustained ventricular tachycardia. Signal averaging of the surface QRS complex was performed in 96 patients with coronary artery disease and ventricular arrhythmias. Twenty eight of them were evaluated by programmed electrical stimulation. Signal average variables were considered abnormal as: 1) the QRS duration as the time from the onset to end point of the QRS vector complex greater than 120 ms, 2) the maximal amplitude of the terminal 40 ms of the QRS vector complex less than 25 microV, 3) the duration of low (less than 40 microV) amplitude signal of QRS vector complex less than or equal to 40 ms. The ventricular late potentials were defined as the pressure of 2 or 3 abnormal averaged variables. Programmed electrical stimulation was performed using single and double extrastimuli at sinus rhythm and at ventricular pacing rates 100, 120, 140 bpm, followed by ventricular burst pacing (3 and 10 consecutive beats) at sinus rhythm. If stimulation of the right ventricular apex did not initiate ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation or two repetitive nonsustained ventricular tachycardias) right ventricular outflow tract stimulation was performed. Sustained ventricular tachycardia was defined as ventricular tachycardia lasting 30 s or requiring termination because hemodynamic compromise. Quantitative comparison of signal averaged variables was performed in patients with inducible versus noninducible ventricular tachycardia and in patients with spontaneous versus non-spontaneous ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259060 TI - [Late ventricular potentials and ventricular arrhythmia in patients with stable ischemic heart disease]. AB - Ischaemic heart disease especially after previous myocardial infarction can predispose to the life-threatening ventricular arrhythmias. Late potentials (LP) are confirmed parameters predicting patients prone to sudden cardiac death in ventricular arrhythmias mechanism. Late potentials registered noninvasively from the body surface were analysed in 86 patients with stable ischaemic heart disease (67 males and 19 females aged 35-67, mean 53 years). Registration of signal average electrocardiograms (SA-ECG) were performed by Simson technic (X, Y, Z orthogonal leads) using identical analysing systems and quantitative SA-ECG criteria in all three participating centers. In all patients ventricular arrhythmias detected on 24-hour ecg Holter monitoring were assessed. The localisation of previous myocardial infarction and echocardiographic assessment of left ventricular function were also analysed in each case. The results of SA ECG were correlated with these clinical findings. Late potentials were detected (according to two or three accepted criteria) in 16 pts (19%), in 53 pts (61%) SA ECG were normal but in other 17 pts (20%) abnormal SA-ECG (according to only one criterium) were registered. Out of these 17 pts with abnormal SA-ECG, 14 pts had prolonged filtered QRS duration as the only incorrect SA-ECG parameter. Comparative analysis between studied groups shows higher incidence of previous Q wave myocardial infarctions in patients with LP and with abnormal SA-ECG than in patients with normal SA-ECG (63% and 71% vs 43% respectively; p less than 0.01). Ventricular arrhythmias observed in studied patients occurred with similar frequency in all groups however in patients with LP and with abnormal SA-ECG complex ventricular arrhythmias were more common than in group with normal SA-ECG (56% and 53% vs 49% respectively: NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259061 TI - [Complex angioplasty (PTCA) in the treatment of coronary artery stenosis]. AB - 56 patients with more than one stenotic coronary artery were treated by complex PTCA with success rate of 96.4%. Complications occurred in 3.6% of pts. Restenoses were found in 9.4% of pts; only one of the dilated arteries were restenosed. 11.3% of pts had repeated PTCA, because of progression of stenosis in other than previously treated artery. Angina occurred earlier in pts with restenoses than in pts with progression of stenoses. Late efficacy (mean 19 months) of complex PTCA was high (90.7%). PMID- 2259062 TI - [Ventricular late potentials--an important prognostic indicator]. PMID- 2259063 TI - [Silent myocardial ischemia--facts and doubts]. PMID- 2259064 TI - [Free serotonin level in the blood of patients with borderline and essential hypertension]. AB - Serotonin appears to play an important part in the pathogenesis of essential hypertension. Various studies have shown, that the metabolism of serotonin may be disturbed in some pathological conditions for example in hypertension. It concerns also the changed mechanisms of uptake and release of serotonin. The certain blood vessels may become more hypersensitive to the vasoconstrictor effects of serotonin in patients with hypertension than in normal subjects. During chronic treatment with ketanserin, S2-serotonergic antagonist, blood pressure is reduced in spontaneously hypertensive rats and in humans. This fact can also indicate indirectly, that that serotonin plays a part in the pathogenesis of essential hypertension. The aim of the study was to determine the concentration of free serotonin (S) in the blood of 15 patients with sustained essential hypertension in the mean age 32.8 +/- 1.8, of 23 patients with borderline essential hypertension in the mean age 29.0 +/- 3.0 and of 10 normal subjects in the mean age 31.1 +/- 1.7 years. Plasma free serotonin was determined by fluorometric method. All patients and controls were investigated at the hospital. They were on normosodium diet, without drugs for last two weeks. The fasting blood samples were collected in the supine position. Free serotonin blood concentration was significantly higher in hypertensive group than in normal subjects. The important difference of serotonin blood concentration between two groups of hypertensive patients was noticed. It was significantly higher in group of patients with sustained hypertension, than in group with borderline hypertension (p less than 0.05). Our results are similar to the observations of other authors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259065 TI - [Cardiologist in the emergency health service]. PMID- 2259066 TI - Morphology and function of the distal part of the afferent arteriole. AB - The morphological features of the juxtaglomerular part of the afferent arteriole presented here are in favor of a bulk fluid flow through the fenestrated endothelium and the urinary space of the glomerulus towards the renin-granulated epithelioid cells and the extraglomerular mesangium. In addition there should be some fluid movement from the glomerular mesangium draining via the glomerular stalk. These flows can be important codeterminants of the interstitial fluid composition around the granular cells and act themselves as a signal to granular or extraglomerular mesangial cells to trigger renin secretion and/or a short-loop (vasculo-vascular) feedback mechanism in governing the glomerular filtration. These studies also provide evidence that the terminal part of the afferent arteriole, consisting of granular cells, lacks the immunoreactive myosin. The role of this vessel segment not only as a putative effector of the tubuloglomerular feedback mechanism, but also as an intrarenal vascular receptor, should therefore be reconsidered. The electrophysiological data presented herein suggest an intrarenal extravascular conversion of Ang I to Ang II in the vicinity of the granular cell. This de novo locally-formed angiotensin II may directly influence the renin secretion, mesangial cell function, and thus tubuloglomerular feedback mechanism and glomerular hemodynamics. PMID- 2259067 TI - The tubuloglomerular feedback mechanism in Milan hypertensive rats. PMID- 2259068 TI - Angiotensin II and the maintenance of GFR and renal blood flow during renal artery narrowing. AB - The time course of the renal blood flow and GFR responses to narrowing of the renal artery in conscious dogs is reviewed. The initial response to this threat to renal perfusion is renal vasodilatation, but within minutes a secondary vasoconstriction mediated by angiotensin II begins to develop. Angiotensin II mediated contraction of mesangial cells is also demonstrable, but this does not apparently reduce the filtration surface area of the glomerular capillaries. The intrarenal effects of angiotensin II restore GFR back to normal within one to two weeks, by which time circulating plasma angiotensin II levels are no longer elevated. In contrast to its effects on GFR, angiotensin II has minimal effects on renal blood flow after stenosis. This may be because, (i) blood flow is mainly determined by the hydraulic resistance of the stenosis; (ii) renal vasoconstriction has relatively little effect on flow due to the particular hemodynamic properties of the stenoses, and (iii) a major site of action of angiotensin II may be within the glomerulus. Thus angiotensin II has a homeostatic role in the maintenance of GFR during renal artery narrowing and one component of this role may involve mesangial contraction. PMID- 2259070 TI - Angiotensin converting enzyme inhibitors and progression of chronic renal failure. AB - Renal failure, once established by loss of a critical amount of functional renal mass, tends to be progressive. A large body of experimental evidence supports the hypothesis that glomerular capillary hypertension is important in the pathogenesis of progressive chronic renal failure of diverse types, including subtotal renal ablation and diabetic nephropathy. Converting enzyme inhibitors are effective in slowing or arresting the progression of glomerular injury in these experimental models, in association with normalization of both systemic and intrarenal pressures. Clinical studies of diabetic nephropathy and chronic renal failure of other etiologies support the concept that these same renal hemodynamic factors are important in human renal disease and that treatment with converting enzyme inhibitors may prove to be a useful therapeutic intervention. Whether the converting enzyme inhibitors have specific advantages over other antihypertensive agents due to beneficial renal hemodynamic effects, as suggested by experimental studies, is a question that awaits further investigation. Furthermore, the pathogenesis of hypertensive glomerular injury is complex and involves the participation of diverse biologic systems. We predict that a wide variety of therapeutic maneuvers, with disparate mechanisms of action, may be effective in arresting or preventing glomerular injury. PMID- 2259069 TI - The renin-angiotensin system and renal function in kidney transplantation. AB - The use of converting enzyme inhibitors (CEI) has permitted us to assess the role of the renin-angiotensin system in the control of arterial pressure and renal function in various conditions. In renal transplant recipients treated by azathioprine and steroids, the occurrence of CEI-induced deterioration of renal function is highly suggestive of renal artery stenosis, whereas renal vasodilatation associated with unchanged glomerular filtration rate in response to CEI is indicative of a significant role of native kidneys. In hypertensive recipients without renal artery stenosis, the absence of renal hemodynamic changes after CEI may be predictive of subsequent chronic rejection. The information provided by CEI is rather different in cyclosporine treated subjects. In this setting, no acute effect of CEI on renal hemodynamics is detectable. Whether the renal response to CEI is similar in cyclosporine when compared to conventionally treated patients with renal artery stenosis remains to be demonstrated. PMID- 2259071 TI - Role of angiotensin II in altered glomerular hemodynamics in congestive heart failure. PMID- 2259072 TI - Morphological observations on the extracellular space in the macula densa of the mouse kidney. AB - Basolateral interstitial spaces (BLIS) of the murine macula densa (MD) are dilated in kidneys fixed either by in vivo glutaraldehyde perfusion or snap freezing-freeze substitution, suggesting that macula densa intercellular spaces may be normally dilated in the functioning nephron. BLIS are also dilated in MD with luminal obstruction with "hyaline" cylinder. This finding might indicate a glomerulo-macular fluid and solute streaming, having an impact on the tubuloglomerular feedback mechanism. PMID- 2259073 TI - Structure of the glomerular mesangium: a biomechanical interpretation. AB - This paper summarizes our current knowledge of the structural details and probable functional significance of the system of contractile filaments in the glomerular mesangium. The description is based mainly on studies of superficial glomeruli of the rat kidney. The contractile apparatus of mesangial cells consists of microfilament bundles located predominantly within mesangial cell processes. The thickest microfilament bundles occur in the juxtacapillary mesangial cell processes, which directly abut the glomerular capillaries. The effector structure of mesangial cell contractility is the GBM. Mesangial cell processes are connected to the GBM either directly or through the interposition of extracellular microfibrils. In general, the contractile system of the mesangium interconnects opposing parts of the GBM. This arrangement is particularly obvious in the juxtacapillary processes, which underlie a mechanical connection between the GBM at the two opposing mesangial angles of a single capillary. The geometry and structural composition of the contractile apparatus of the mesangium indeed suggest a static rather than a dynamic function. In conjunction with the GBM, the mesangial contractile apparatus seems capable of supporting sufficient wall tension to counteract the distending forces acting across the capillary walls; the apparatus also seems capable of directly balancing the distending forces on the perimesangial walls. Assuming that mesangial cells are capable of isotonic contractions, the effect of such a contraction on capillary diameter and, consequently, on filtration area would be small. PMID- 2259074 TI - Angiotensin I-forming angiotensinogenases in extrarenal vasculature and in the kidney. AB - The intention of this study was to characterize angiotensin I-forming angiotensinogenases (AIFAs) in rat extrarenal arterial walls and to clarify whether these enzymes are also present in the kidney. A further aim was to identify AIFAs in human vasculature and to establish whether they are affected in essential hypertension. Sprague-Dawley rats and vascular sections of patients undergoing corrective surgery were studied. Enzyme kinetic assays were performed using angiotensin I radioimmunoassay and purified natural angiotensinogens. Fast protein liquid chromatography was employed for biochemical characterization. A series of AIFAs with various isoelectric points, molecular weights and pH optima was detected in rat extrarenal vascular and, with differing distributions of enzyme activities, in renal tissues. In extrarenal arteries the main form of renal renin was present with a relatively low activity only. AIFAs were also demonstrable in human extrarenal vasculature and behaved like plasma renin in essential hypertension. The results indicate the existence of an intrinsic human vascular RAS in extrarenal (and renal) arteries. Extrarenal arterial AIFAs are not generally stimulated in essential hypertensives, as previously postulated. PMID- 2259076 TI - Calcium-activated chloride conductance of mesangial cells. PMID- 2259075 TI - On the intrarenal regulation of renin release from the juxtaglomerular apparatus. PMID- 2259077 TI - Different responses of cortical and juxtamedullary arterioles to norepinephrine and angiotensin II. AB - Cortical (C) and juxtamedullary (JM) glomerular blood flow were measured with intravitalmicroscopic techniques in the split hydronephrotic kidney of female Wistar rats under Inactin anesthesia. Intravenous injection of small, equivalent pressor doses of norepinephrine (NE) and angiotensin II (Ang II) reduced the diameter of C afferent arterioles by -16 +/- 2.4% and -14 +/- 1.9%, respectively, whereas that of JM afferent arterioles was reduced by only -3.8 +/- 2.7% and -3.8 +/- 1.5%. Blood flow under NE and Ang II was reduced in C glomeruli by -42 +/- 4.9% and -37 +/- 4.0%, respectively, but in JM glomeruli was reduced by -10 +/- 6.2% and -8.6 +/- 2.9% of control. Perfusion pressure reduction during NE or Ang II infusion to preinfusion values revealed autoregulatory behavior only in C glomeruli. In a second series of experiments cyclooxygenase inhibition by local administration of indomethacin (2.8 x 10(-5) M) induced C and JM vasoconstriction. The effects of NE and Ang II during local application of indomethacin were variable but different responsiveness of C and JM vessels disappeared. We assume that the differences in NE and Ang II responsiveness between C and JM vessels under control conditions are caused by a high prostaglandin content or sensitivity, particularly of JM vessels in the hydronephrotic kidney. PMID- 2259078 TI - Arteriolar renin and vascular effects of angiotensin II in juxtamedullary nephrons. AB - The SJMNs made accessible in the in vitro juxtamedullary nephron preparation possess an arteriolar renin and Ang II distribution similar to other nephron populations; renin-rich cells prevail in the JAA. Physiological studies have documented that exogenous Ang II constricts both pre- and postglomerular vessels of SJMNs. However, Ang II predominantly increases afferent resistance along the JAA. A functional interaction between Ang II and prostaglandins is likely to occur in preglomerular vessels and deserves further assessment. An additive, functional interaction was demonstrated between Ang II and autoregulation in afferent arterioles. Calcium channel blockers interfere with Ang II-induced constriction only in preglomerular vessels of SJMNs. PMID- 2259079 TI - Renal hemodynamic regulation by the renin-secreting segment of the afferent arteriole. PMID- 2259080 TI - Interactive effects of angiotensin II on renal hemodynamics and tubular reabsorptive function. PMID- 2259081 TI - Effect of a converting enzyme inhibitor, angiotensin II, and saralasin on glomerular hemodynamics. PMID- 2259083 TI - Angiotensin II and thromboxane in the regulation of blood pressure and renal function. AB - In experiments in anesthetized rats, the hypothesis that angiotensin II (Ang II) infusion released thromboxane (TxA2) which modulated the systemic and renal vasoconstriction was tested. Intravenous Ang II (500 ng.kg-1.min-1) increased MAP by 35 +/- 3 mm Hg and the excretion of TxB2 (P less than 0.03), whereas a similar pressor infusion of phenylephrine did not increase TxB2 excretion. A TxA2 receptor antagonist (TxRA) SQ-29,548 (8 mg.kg-1.hr-1) or pretreatment with a thromboxane synthesis inhibitor (TSI), UK-38,485 (50 mg.kg-1.day-1 x 3) blunted (P less than 0.005) the pressor response to 12 +/- 2 and 11 +/- 2 mm Hg, respectively, whereas TxRA did not modify the pressor response to phenylephrine. Infusion of Ang II at a dose of 50 ng.kg-1.min-1 reduced the GFR and increased the filtration fraction and renal vascular resistance. TxRA blunted (P less than 0.01) these effects of Ang II. IN CONCLUSION: 1.) Ang II releases TxA2 within the kidney independent of hypertension; 2.) TxA2 can mediate much of the pressor and renal hemodynamic responses to Ang II. PMID- 2259082 TI - Effect of angiotensin and other pressor agents on tubuloglomerular feedback responses. AB - Experiments were performed in anesthetized rats to examine the effect of an intravenous infusion of norepinephrine or vasopressin on the tubuloglomerular feedback (TGF) response of stop flow pressure (PSF). During infusion of norepinephrine at an average rate of 107.5 ng/kg min, mean femoral arterial pressure (MAP) increased from 102.1 +/- 3.55 to 113.7 +/- 3.44 mm Hg and PSF-max increased from 7.45 +/- 1.13 to 9.95 +/- 1.19 mm Hg. When MAP was returned to control by a suprarenal aortic clamp PSF-max was 5.64 +/- 1.09 mm Hg (NS vs. control). Similarly, at an infusion rate of 226.5 ng/kg min PSF-max was not significantly different from control (6.79 +/- 1.61 mm Hg). V1/2, the half maximum flow rate, was not altered by norepinephrine whether MAP increased or was kept constant. Infusion of vasopressin at the pressor dose of 13.0 mU/kg min increased MAP by about 25 mm Hg and raised PSF-max from 6.56 +/- 0.84 to 14.45 +/ 1.54 mm Hg. However, when MAP was returned to normal PSF-max was 5.41 +/- 0.75 mm Hg (NS). Our data show that in contrast to angiotensin II, norepinephrine and vasopressin do not augment TGF responses when a rise in MAP is prevented. Angiotensin II appears to play a specific role in altering the sensitivity of the TGF mechanism. PMID- 2259084 TI - Adrenergic influences and interactions with angiotensin II. AB - Increasing evidence indicates the existence of a complex interplay between the angiotensin and adrenergic nervous systems within the kidney. Since both of these vasoconstrictor systems are integrally involved in the maintenance of systemic blood pressure and fluid and electrolyte homeostasis, it is not surprising that each might influence the other vis-a-vis their mutual capacity to alter the physiologic determinants of glomerular filtration. PMID- 2259086 TI - Influences of angiotensin on renal function in renal vascular hypertension. AB - The scope and the magnitude of the roles which angiotensin plays in the generation and maintenance of elevated blood pressure in models of renal vascular hypertension are continuing to expand. It is now clear that specific angiotensin dependent mechanisms contribute importantly to the pathophysiology of hypertension and altered renal function in models of two-kidney, one clip hypertension in rats. The generation of angiotensin in the local intrarenal environment of the kidney is a new and potentially important mechanism contributing to altered renal function in these models. Application of antagonists of the renin-angiotensin system to rat models of renal vascular hypertension indicate that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney. Further, angiotensin may attenuate the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney. Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicate that angiotensin may contribute importantly to the pathophysiology of hypertension in these models by altering or impairing the ability of the nonclipped or normal kidney to excrete sodium and volume. PMID- 2259085 TI - Role of angiotensin in the renal vasoconstriction observed during the development of genetic hypertension. AB - Studies have examined renal function to determine the role of the kidney in the pathogenesis and maintenance phases of hypertension in the Okamoto-Aoki strain of spontaneously hypertensive rat (SHR). As compared to age-matched Wistar-Kyoto rats (WKY), 4- to 6-week old SHR are moderately hypertensive and have a reduced glomerular filtration rate (GFR) and renal blood flow (RBF), and an increased renal vascular resistance. Cross-breeding studies indicate the reduction in RBF and GFR in young SHR is genetically linked to the hypertension and thus may be of primary pathogenetic importance. The combination of an elevated vascular resistance and reduced RBF and GFR in young SHR implicates increased activity of a vasoconstrictor system(s), decreased activity of a vasodilator system(s), or both. Observations from several laboratories support the notion that endogenous angiotensin II contributes to the renal vasoconstriction in young SHR during the developmental phase of hypertension. Acute and chronic inhibition of angiotensin converting enzyme reduce arterial pressure, reduce renal vascular resistance and increase renal blood flow in young and adult SHR. Renal vascular tone in SHR is more dependent on angiotensin converting enzyme activity than that in WKY. The ability of angiotensin converting enzyme inhibitors to produce renal vasodilation may be responsible, at least in part, for its antihypertensive effects. Other studies indicate that renal vascular reactivity to angiotensin II is exaggerated in young SHR. The strain differences in renal reactivity to angiotensin II can be abolished by cyclooxygenase inhibition with indomethacin, indicating that endogenous prostanoids counteract some of the constrictor action of angiotensin II, with more pronounced buffering activity in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259087 TI - [Intragastric blood flow in the etiology of duodenal ulcer--new aspects of surgical treatment]. AB - In the experiment on dogs and in patients with duodenal ulcer disease, it was established that the regulation of acid production besides the vagal nerves was mediated by the intragastric gastrin transport with the blood flow. A method of preoperative diagnosis of the intensity of intragastric blood flow permitting to define more accurately the indications for the choice of a method for surgical treatment has been developed. Supplementation of the selective proximal vagotomy with circular mucosectomy at the boundary between the antrum and body of a stomach enhances the effectiveness of operation due to reduction of the antral gastrin influence on the acid-producing zones of the stomach. PMID- 2259088 TI - [Pathogenesis of acute ulcers of the digestive tract in post- operative suppurative-septic complications]. AB - In studying the pathogenesis of acute gastric and duodenal ulcers arising in operated patients against the background of purulent-septic complications, the specific signs distinguishing them from stress-ulcers, which develop in response to surgical aggression, were revealed. They are: the absence of inflammatory reaction in the gastric mucosa, its ischemia, hypo- and achlorhydria with reduction in the proteolytic activity of gastric juice. PMID- 2259089 TI - [Hemorrhagic shock in acute gastric hemorrhage]. AB - On the basis of the analysis of 1023 clinical observations of hemorrhagic shock in acute gastric hemorrhage, the modern notions about the mechanisms of its development, peculiarities of the clinical course, depending on nature and volume of blood loss are stated. A scheme for intensive anti-shock therapy has been developed. The lethality after 1892 emergency operations was 3%, and in ulcer with hemorrhagic shock after 547 operations--9.3%. PMID- 2259090 TI - [Intravascular laser irradiation of blood in the treatment of patients with acute peptic ulcer hemorrhage]. PMID- 2259091 TI - [Characteristics of the clinical course and surgical treatment of duodenal ulcer in young patients]. AB - In a work, the peculiarities of clinical picture, surgical tactics and long-term results of the organ-preserving operations in 698 patients with duodenal ulcer disease operated on at the age under 30 years are analysed. It was established that the latent course and high incidence of acute complications manifesting the disease for the first time were the main peculiarities of duodenal ulcer in young patients. Vagotomy together with the other methods of surgical treatment of duodenal ulcer can be successfully used in young patients as an elective, or emergency surgical aid. PMID- 2259092 TI - [Value of the natural killer cell count in the peripheral blood of patients with surgical diseases of the stomach and duodenum]. AB - In patients with the ulcer disease, the reduction in number of natural killer cells (NKC), which aggravated after gastric resection, was revealed. At discharge of the patients, the NKC number normalized. Reduction in the NKC number was revealed in development after the operation of acute anastomositis. The lowest NKC levels were revealed in patients with stage III and IV gastric cancer. PMID- 2259093 TI - [Electric activity of the proximal part of the digestive tract in the normal state and after pyloroplasty and transsection of the ligament of Treitz in dogs]. AB - It is shown that the normal amplitude-frequency characteristics of the duodenojejunal flexure differ from those of the duodenum. After pyloroplasty, the electrical activity of the antrum do not change. At the region of the duodenojejunal flexure, the intensification of the electrical activity, increase in the amplitude, frequency of the slow wave and peak potentials occur. Supplementation of pyloroplasty with transection of the Treitz ligament led to suppression of the electrical activity of the antrum and duodenojejunal flexure. A conclusion about the close functional interrelation between the pylorus and duodenojejunal junction has been drawn. PMID- 2259094 TI - [Effect of vagotomy on intramural gastric plexus--the problem of reinnervation of the stomach after vagotomy]. AB - In dogs, only fundus and body, or antrum were denervated. At the period of up to 5 years after vagotomy, no complete parasympathetic reinnervation of the stomach occurs. PMID- 2259095 TI - [Morphofunctional changes in the digestive tract after simulating long-term disorders of blood outflow from the abdominal organs]. AB - In the process of studies on 16 dogs with the prolonged impairement of venous blood outflow from the abdominal organs being modelled, the development of dystrophic-changes in the walls of the organs of the alimentary canal, and as well the formation of the adhesions along the course of the veins was noted. A degree of pronouncement of the mentioned changes depends on the structure of the abdominal organs. PMID- 2259096 TI - [Surgical treatment of patients with bleeding stomach ulcers]. AB - The results of treatment of 480 patients with bleeding gastric ulcers are presented. The more wide use of the Billroth-I gastric resection (135 patients) versus Billroth-II gastric resection (54 patients) permitted to reduce the incidence of early postoperative complications from 42.6 to 15.6%, and lethality- from 24.1 to 3.7%. The use of therapeutical tactics based on the endoscopic characteristic of a source of bleeding, evaluation of the dynamics of pathological process, severity degree of blood loss with regard for location and size of the ulcers, and with regard as well for the differential approach to the choice of a method of operative intervention permitted to reduce the total lethality from 22.8 to 7.2%, lethality after the emergency operations--from 34.4 to 13.5%, total postoperative lethality--from 23.8 to 9.5%, to increase the specific weight of radical operations from 43.8 to 69.7%, reduce lethality after conservative treatment of the patients from 21.5 to 3.7% when compared with that in active-expectant tactics. PMID- 2259097 TI - [Functional results of gastric resection in peptic ulcer]. AB - The results of surgical treatment of 406 patients with gastric and duodenal ulcers are analysed. The postoperative lethality was 0.49%. The author has used the technique of gastric resection with the artificial sphincter formation from the seromuscular flap of a gastric stump. At the late period after the operation, the mild degree dumping-syndrome developed in 2.6%, reflux-gastritis--in 5% of the patients. PMID- 2259098 TI - [Clinical, radiologic and endoscopic aspects of duodenoplasty]. AB - The authors performed the selective proximal vagotomy in combination with the ulcer excision and duodenoplasty in 233 patients in complicated forms of duodenal ulcer disease. The clear indications for this type of intervention have been established. The high effectiveness of the pylorus-preserving operations is noted. Improvement of the techniques for local removal of an ulcer is a reserve for improving the results. PMID- 2259099 TI - [Duodenogastric reflux after organ-sparing operations in complicated duodenal ulcer]. AB - On the basis of treatment of 105 patients operated on for complicated duodenal ulcer disease, it was established that performance of the organ-preserving operation with the ulcer excision supplemented with the pylorus-restoring and pylorus-preserving intervention permitted to reduce considerably the incidence of duodenogastric reflux. PMID- 2259100 TI - [Late results of surgical treatment of perforated pyloroduodenal ulcers]. AB - The results of treatment of 171 patient operated on for perforative pyloroduodenal ulcer in follow-up of up to 12 years are analysed. After closure of a perforative ulcer, the bad result was noted in 51.6% of the patients. The performance of the different types of vagotomy contributed to stable recovery in 88.3% of the patients. PMID- 2259101 TI - [Rehabilitation of patients and healing time of duodenal ulcers after organ sparing operations with vagotomy]. PMID- 2259102 TI - [Correction of functional gastrostasis after surgical treatment of peptic ulcer]. PMID- 2259103 TI - [Effect of surgical stress on cytotoxicity of the natural killer cells]. PMID- 2259104 TI - [Pyloric sphincter and its role in the regulation of digestive processes]. PMID- 2259105 TI - [Causes of unsatisfactory results of selective proximal vagotomy and the choice of corrective operation]. AB - Analysis of the causes of the unsatisfactory results of SPV in 39 patients has shown that the leading ones among them were the preservation of a high level of acid formation, antral stasis, chronic duodenal obstruction resulting from the extravasal compression of the celiac trunk and celiac ganglioneuritis. When choosing the corrective operation, it is necessary to consider the main factors causing the occurrence of an unsatisfactory result. PMID- 2259107 TI - [Organ injuries during gastrectomy in peptic ulcer]. PMID- 2259106 TI - [Injuries of the common bile duct and pancreatic duct during gastrectomy]. PMID- 2259108 TI - [Errors and hazards of endoscopic procedures]. PMID- 2259110 TI - [Causes of death after vagotomy]. PMID- 2259109 TI - [Mallory-Weiss syndrome]. PMID- 2259112 TI - [Duodenoptosis as a condition for the development of chronic duodenal obstruction]. PMID- 2259111 TI - [2 cases of long-term remission after conservative treatment of inoperable cancer of the stomach]. PMID- 2259113 TI - [Endoscopic removal of giant gastric polyps]. PMID- 2259114 TI - [Treatment of concealed perforated duodenal ulcers complicated by subhepatic abscesses]. PMID- 2259115 TI - [Characteristics of blood flow in the stomach and duodenum of patients with recurrent ulcer]. PMID- 2259117 TI - [Acute erosive-ulcerative lesions of the gastric and duodenal mucosa in patients with obstructive jaundice]. PMID- 2259116 TI - [Detection of Campylobacter pylori in patients with peptic ulcer as a criterion of the effectiveness of treatment with ultraviolet laser irradiation]. PMID- 2259118 TI - [Cancer of the stomach in a patient after selective proximal vagotomy]. PMID- 2259119 TI - [Foreign bodies of the digestive tract]. PMID- 2259120 TI - [Acute adhesive intestinal obstruction in a patient with multiple postoperative abscesses of the abdominal cavity]. PMID- 2259121 TI - [Use of low-energy, non-coherent red light in the comprehensive treat ment of acute and chronic peptic ulcers]. PMID- 2259122 TI - [Perforation of acute peptic ulcer of gastroenteroanastomosis two months after subtotal gastrectomy]. PMID- 2259123 TI - [Treatment of stomach and duodenal ulcers using copper vapor laser]. PMID- 2259124 TI - [Removal of a foreign body from the upper digestive tract]. PMID- 2259125 TI - [Wild cherry bezoar as a cause of acute stomach ulcers]. PMID- 2259126 TI - [Bleeding from multiple acute ulcers of the stomach and intestine in a patient with Zollinger-Ellison syndrome]. PMID- 2259127 TI - [Development of necrotizing enteritis after selective proximal vagotomy]. PMID- 2259128 TI - [Gangrenous cholecystitis after gastrectomy]. PMID- 2259129 TI - [Rare complication after gastric resection]. PMID- 2259130 TI - [Effect of mobilization of the posterior cardial wall on the completeness of selective proximal vagotomy]. AB - On the basis of the revealed on 76 cadavers by means of preparation neural + connections of the posterior wall of the gastric cardia and celiac plexus and results of the selective proximal vagotomy (SPV) performed in 111 patients with the duodenal ulcer disease, it was established that mobilization of the posterior wall of the cardia provided the full-value denervation of the stomach and prevented the ulcer recurrency. PMID- 2259131 TI - [A rare case of foreign body migration]. PMID- 2259132 TI - [Surgical treatment of patients with acute peptic ulcer hemorrhage]. PMID- 2259133 TI - [Rare complication of peptic ulcer at the gastroduodenal anastomosis]. PMID- 2259134 TI - [A case of gastric phlegmon]. PMID- 2259135 TI - [Modification of the esophago-intestinal anastomosis]. PMID- 2259136 TI - [Reconstructive surgery on the stomach after initial resection using the Ia. D. Vitebskii method]. PMID- 2259138 TI - [A method of pyloroduodenoplasty]. PMID- 2259137 TI - [Intramural supramucosal omentogastropexy in the surgical treatment of stomach ulcer]. PMID- 2259139 TI - [A method of percutaneous transaortic selective catheterization of the iliac and femoral arteries]. PMID- 2259140 TI - [A vascular perforator]. PMID- 2259141 TI - [Clinical aspects, diagnosis and treatment of acute perforated gastroduodenal ulcers]. PMID- 2259142 TI - [Changes in the immunologic status of patients with congenital heart defects after surgical procedures using extracorporeal circulation]. PMID- 2259143 TI - [Expert medical evaluation of work capacity after surgery for chronic constrictive pericarditis]. PMID- 2259144 TI - [Classification of the criteria of surgical risk]. PMID- 2259145 TI - [Compression anastomoses in gastrointestinal surgery using a device made of alloys with form "memory"]. PMID- 2259146 TI - [Surgical treatment of burn sequelae in the region of the anterior and lateral surfaces of the knee joint]. PMID- 2259147 TI - [Cicatricial pyloric stenosis after chemical burns of the stomach in children]. PMID- 2259148 TI - [Acute dilatation of the stomach in a child]. PMID- 2259150 TI - [Small-intestinal obstruction caused by peritoneo-omental hernia]. PMID- 2259149 TI - [Neurofibroma of the appendix]. PMID- 2259151 TI - [Non-parasitic cyst of the spleen in a child]. PMID- 2259152 TI - [Surgical treatment of Mauriac syndrome]. PMID- 2259153 TI - [Anaerobic infection in infants]. PMID- 2259154 TI - [Tail-like appendage in a newborn infant]. PMID- 2259155 TI - [One-stage consecutive laser recanalization, balloon dilatation and nitinol-frame endoprosthesis of the occluded iliac artery]. PMID- 2259156 TI - [Traumatic rupture of the main right bronchus in a child]. PMID- 2259157 TI - [Embolization of the bronchial artery in pulmonary hemorrhage]. PMID- 2259158 TI - [Liver abscess in a child after appendectomy]. PMID- 2259159 TI - [Embolization of hepatic hemangioma in a child]. PMID- 2259160 TI - [Perforation of the common bile duct in a child]. PMID- 2259161 TI - [Hemangioma of the liver associated with calculous cholecystitis]. PMID- 2259162 TI - [Surgical treatment of acute forms of Hirschsprung disease and total intestinal aganglionosis in infants]. PMID- 2259163 TI - [Surgical treatment of anorectal developmental defects in children (review of foreign literature)]. PMID- 2259165 TI - [Possibilities of current methods of diagnosis and surgical treatment of hepatic cysts]. PMID- 2259164 TI - [Use of lasers on aluminum-yttrium garnet with neodymium in clinical practice]. PMID- 2259166 TI - [Aleksandr Alekseevich Bobrov (1850-1904)]. PMID- 2259167 TI - [Comparative evaluation of various types of intestinal sutures in newborn infants and young children]. AB - The article deals with the results of experimental and clinical studies. The mechanical strength of the coats of the intestinal wall was tested in cadavers of newborns and on basis of the findings a variant of a single-layer +sero-muscular submucous intestinal suture was suggested. It was studied later in comparison with other types of sutures in experiments on 140 immature rats. All sutures were applied by microsurgical techniques. The results of the clinical use of the suggested suture in newborns and infants were analysed in comparison with previously applied sutures. Four groups were set apart: 1st--double-row interrupted suture (45 patients); 2nd--single-row suture applied at the edge through all coast (15); 3rd--Mateshuk's single-row suture (7); 4th--single-row +sero-musculo-submucous suture applied by microsurgical techniques (32). Complications were revealed on the part of the anastomosis: 1st group--24 (53.3%), 2nd group--11 (73.3%), 3rd group--4 (57.1%), 4th group--1 (3.1%). The results of macro- and microscopic study of the anastomoses in fatal cases suggest that the +sero-musculo-submucous intestinal suture provided the most favourable conditions for healing of the anastomosis. PMID- 2259168 TI - [Inter-intestinal compression anastomosis in children]. AB - Enterostomy of the afferent intestine with preliminary formation of an intestinal anastomosis with the efferent loop was carried out in 11 children. The anastomosis was created by means of a compression device of an alloy "with shape memory". Among the children who underwent operation 7 were newborns with intestinal atresia and 4 were children of an older age with peritonitis and perforation of the intestine. No operative complications were encountered. An intestinal anastomosis with a fistula-bearing intestine allows multiple complications of routine enterostomy to be avoided. PMID- 2259169 TI - [Predicting the course of wound healing after appendectomy using the hydroxyproline test]. AB - A test for free hydroxyproline in blood plasma, urine, and wound exudate was conducted in a group of children who were operated on for acute catarrhal and destructive forms of appendicitis in an uncomplicated or complicated post operative wound process. The changes in the concentration of the biochemical index were most regular in the wound exudate. Free hydroxyproline increased after the operation, reached highest values in 48 hours, and then reduced coming close to the control values 5-6 days after. In wound complications it increased three- to four-fold as compared to the control values, which could serve as an informative test in predicting the course of the postoperative wound process in children. PMID- 2259170 TI - [Rehabilitation of children with external intestinal fistula]. AB - Experience in the treatment of 153 children with external intestinal fistulas is discussed. In 6 children the intestinal fistulas occurred as the result of a pyodestructive process in the abdominal cavity, in 147 children they were formed for therapeutic purposes. The choice of the method of treatment is individual and is determined by the character of the fistula. A magneto-++-compressive inter intestinal++ anastomosis (MCIA) was formed for exclusion of the intestinal fistulas. Under conditions of peritonitis in gun-barrel enterostomy intraoperative formation of the MCIA can be undertaken. The method was applied in 21 children, no complications occurred. In closure of gun-barrel enterostomy an operative method was elaborated with preservation of the greater part of the magneto-++-compressive anastomosis. PMID- 2259171 TI - [Use of heterogenous materials in the surgical treatment of fecal incontinence in children]. AB - Operations were carried out on 40 male and female patients with stage III incontinence of feces from 1970 and through 1980. Their ages ranged from 8 to 14 years. The disease was caused by unsuccessful correction of anorectal developmental anomalies. The following operations were performed: after Wreden on 16 patient, after Faerman on 12, after Makhov on 8 and after Thiersch on 4 patients. The follow-up periods ranged from 2 to 6 years. A recurrence was found in all of the children. Y-shaped sphincteroplasty and a modified Wreden's operation with the use of heterogeneous material have been developed and introduced into practice in the clinic since 1983. Twenty two patients with stage III incontinence of feces were operated on, the result was positive in the majority of cases. PMID- 2259172 TI - [Condition of the anal sphincter in patients with anorectal anomalies based on electromyographic data]. AB - The condition of the sphincter ani externus muscle was studied on basis of electromyographic examination of 130 patients with anorectal developmental anomalies who were treated at the clinic during the period between 1984 and 1988. It is noted that electromyography allows the electrical activity of the muscle to be appraised authentically. The authors emphasize that malposition of the sphincter ring and its anomalous relationship with the surrounding structures was encountered in the preoperative period in 47.4% of children with developmental anomalies of the anorectal zone. This circumstance must be taken into account in choosing the site to which the rectum will be brought down during the operative intervention. Examination of 54 patients with clinical functional disorders in the late-term periods after surgical correction showed pathology of the sphincter ani externus muscle to be the principal etiological factor in the development of these disorders; it was revealed in 87.3% of cases. PMID- 2259173 TI - [Stimulation tonometry of the functional segment of the large intestine in children]. AB - In view of the frequently encountered functional changes of the distal part of the large intestine in children and the need for early purposeful diagnosis and rehabilitation of patients with this pathological condition, this part of the large intestine, responsible for adaptation, evacuation, and closure, should be distinguished as an independent functional part of the large intestine (FPLI). The frequent use of direct electrostimulation of the FPLI and the absence of an objective control over its efficacy allowed the authors to develop a new diagnostic method--stimulation tonometry of the FPLI consisting in conducting tonometry of the FPLI during direct dynamic electrostimulation of the intestine in comparison with background study. The method allows a differentiated approach to FPLI electrostimulation depending on the character of the pathological changes. Comparative characteristics of altered intestinal tonometry is give. PMID- 2259174 TI - [Prolapse of the urethral mucosa in girls]. AB - In the recent 9 years 39 girls aged from 2 to 10 years were treated at the clinic for prolapse of the urethral mucosa. Among them 24 had circular and 15 had segmental prolapse. The disease was encountered most frequently between 6 and 10 years of age, predominantly in the summer. Complex treatment was started with nonoperative measures which were followed by operation if the prolapse persisted or recurred. Spontaneous reduction of the mucosa occurred in 6 of 22 children who were treated by nonoperative measures, in 3 cases the effect was temporary and a recurrence developed. Operative excision of the mucosa was carried out in 36 girls. The results were good. The article discusses the etiopathogenesis of the disease and analyses the morphological changes in the removed urethral mucosa. PMID- 2259175 TI - [Urinary diversion in infants]. AB - The article generalizes the experience in the treatment of over 500 children, aged from hours to 5 months, with various developmental anomalies of the urinary system. Different variants for draining off the urine were applied in 142 patients. Urethral, vesical, and supravesical methods are characterized. The indications for their use in the newborns and infants are formulated. Preference is given to the supravesical methods, among which T-ureterocutaneostomy and suspended ureteropyelostomy are optimal. The operative techniques are described. Complications occurred in 10 children: urinary dermatitis (3), cicatrization of the stoma (2), separation of the sutures of the main wound (2), stenosis of the stoma (1). The author concludes that draining off urine in the newborn with obstructive uropathy is advisable before radical correction of the anomaly. PMID- 2259176 TI - [Computer-assisted evaluation of renal blood supply in children and its clinical value]. AB - The blood supply to the kidneys was studied in 106 children with urological diseases from angiograms. Computer analysis of 322 angiograms of patients with renal hypoplasia, dysplasia, hydronephrosis, megaureter, and abnormal mobility of the kidney was carried out. The results of angiography of a healthy kidney in 64 children were used to determine the normal parameters. The author gives a quantitative appraisal of the area of the kidney and its vessels, the calculation of the percentage of kidney vascularization, determination of the area of the renal cortex, the area of its vessels and percentage of vascularization, and the diameter of the large renal vessels. The study showed that the most informative parameters of the angiograms are as follows: the area of the renal vessels and its cortex, the percentage of vascularization of the Kidney and its cortex. Renal hypoplasia, dysplasia, megaureter, and hydronephrosis are characterized by different variants of disturbed blood supply of various severity. PMID- 2259177 TI - [Venous drainage of the testis and the causes of the development of varicocele in children]. AB - The article discusses the results of angiological examination of 42 children with primary and 13 with recurrent varicocele by the method of ++trans-scrotal antegrade venotesticulography. Three groups of patients were distinguished: I- with drainage of blood into the left testicular vein, II--with drainage into the left cremasteric vein, III--with simultaneous drainage into the two above indicated veins. Incompetence of the valvular apparatus of the left testicular vein and impaired blood drainage from the left external iliac vein with the development of retrograde flow of blood along the left cremasteric vein are the most frequent causes of varicocele in children. PMID- 2259178 TI - [Diagnosis and treatment of biliary tract obstruction in children with biliary atresia]. AB - Fifty children from one month to 14 years of age were examined and subjected to surgical treatment. Atresia of the bile ducts was diagnosed in 34 of them, hypoplasia of the bile ducts in 5, and a cyst of the choledochus in 11. Biliary atresia was managed by different variants of portoenterostomy, mostly after Kasai I, and two operations of cholecystojejunostomy were conducted in the so-called correctable type of atresia. 5 patients with biliary hypoplasia were treated by cholecystectomy, lavage of the bile ducts, and denervation of the hepatic artery. The following operations were carried out on 11 patients with a cyst of the choledochus: extirpation of the cyst with subsequent hepaticojejunostomy in 4, cystojejunostomy in 5, and cystoduodenostomy in 2 patients. Ultrasonic examination of the liver was undertaken in all 50 patients with impaired patency of the biliary tract as a screening test. Nine patients died in the postoperative period. PMID- 2259179 TI - [Herniotomy as a cause of male infertility]. AB - The article deals with 8 cases of iatrogenic obstruction of the vas deferens after herniotomy for inguinal hernia, the consequence of which was sterility. Anastomosis of the vas deferens was formed in 6 patients by means of precision microsurgical manipulations; the spermatological indices improved markedly in 3 of them, which was evidence of restored passage of the semen. To avoid injury to the spermatic cord, the author recommends microsurgical techniques in treatment of the hernial sac in children with congenital inguinal hernia. PMID- 2259180 TI - [Abdominal non-Hodgkin's lymphoma in children]. AB - Study of the clinical manifestations and the results of treatment of abdominal lymphomas in 58 children showed that the poor results of therapy were due first of all to the high proportion (67.2%) of generalized forms by the time of their detection. Among the patients who were under observation, the 3-5-year survival was 41.3%. Late recognition of the disease was linked with the absence of proper oncological alertness among the physicians. Profound preventive examinations with the wide use of modern diagnostic techniques will be conducive to an early diagnosis of this pathological condition and improvement of the results of treatment. PMID- 2259181 TI - [Hemostatic potential during the development of post-mastectomy edema]. AB - The work deals with the study of the mosaic character of the hemostatic potential, connected with the development of a localized pathological process, taking postmastectomy edema in illustration. It is shown that this condition is an example of the manifestation of the RASK system mosaics in one organism in pathology. It should be pointed out that the degree of the development of the local DVS syndrome changes significantly some of the RASK system parameters at the level of the whole organism. This is evidence that normalization of the microcirculatory processes in the edematous extremity will be an important measure in complex treatment of postmastectomy edema. It will considerably lower the risk of general disorders of the RASK system. Parameters determined in the blood collected from the extremity on the side of the operation will serve as controls of the efficacy of the applied therapeutic measures. PMID- 2259182 TI - [Immunologic disorders in children with developmental thoracic defects]. AB - As the result of immunological examination of 21 children with developmental defects of the chest and analysis of the course of the postoperative period in 136 children, among which 36 had hereditary syndromes of systemic connective tissue dyshistogenesis, it was found that suppurative complications of thoracoplasty, which are encountered in 15% of children with isolated developmental chest defects and in 33.3% of those with the above mentioned syndromes, were caused to a great measure by disorders of the immune status. The most serious immunological deviations were encountered in the Marfan syndrome due to impaired phagocytic activity of neutrophils and monocytes, decreased number of T, T active, and B lymphocytes, and diminished function of T helpers. In unclassified complexes of developmental defects with Marfaneic ++ phenotypes, the immunological disorders were similar, but less deep. In the Ehlers-Danlos syndrome, a decrease of the number of immunocompetent cells, function of T helpers, and neutrophils was mainly revealed. In isolated forms of funnel chest the function of monocytes and the number of immunoglobulins are mainly decreased. PMID- 2259183 TI - [Surgeries on the carotid arteries]. AB - The article lays emphasis on the main causes of restenosis after endarterectomy from the bifurcation of the carotid artery and shows the methods of its prevention. A new method for endarterectomy of the bifurcation of the carotid artery is suggested, which consists in reimplantation of the internal carotid artery. The authors claim this method to be optimal in combined affection: atherosclerotic constriction of carotid artery bifurcation and pathological tortuosity of the internal carotid artery. The authors possess an experience in 351 operations on the carotid arteries, 177 of them were conducted for loops and kinks of the carotid arteries; 152, for endarterectomy in atherosclerotic affection of the carotid arteries; and 22 for other, less frequently encountered affections of the carotid arteries. PMID- 2259184 TI - [Splenectomy in the treatment of severe generalized myasthenia gravis (first experience)]. AB - The authors discuss the results of splenectomy carried out on 20 patients with generalized myasthenia in whom previous complex treatment including thymectomy, corticosteroid and azathioprine therapy, repeated courses of plasmapheresis during medication with anticholinesterase agents, did not cause any essential improvement. Different values of homeostasis and immunological status were studied before and in different periods after splenectomy. The condition improved in 65% of patients, which was confirmed by the results of myography; the doses of corticosteroids and anticholinesterase agents were reduced. Bearing in mind the severe condition of patients selected for splenectomy, it is recommended to treat them only in medical centers possessing sufficient experience in treatment of myasthenia. The indications and contraindications for splenectomy in complex treatment of myasthenia must be specified further. PMID- 2259185 TI - Hemodialysis, membrane-related neutrophil dysfunctions, and pentoxifylline--a pilot study. AB - Hemodialysis treatment is associated with activation of neutrophil granulocytes. Pentoxifylline has been shown to inhibit neutrophil activation in vitro and in vivo. We investigated the effect of pentoxifylline on leukocyte and platelet counts and on plasma levels of extracellularly released neutrophil elastase and lactoferrin during a four-hour hemodialysis treatment. Eight patients received 400 mg of pentoxifylline or placebo orally twice a day over 14 days and an additional dose of 400 mg of pentoxifylline intravenously during hemodialysis. Each subject served as his own control in a randomized, double-blind, cross-over study. Combined oral and intravenous treatment with pentoxifylline prevented neither leukopenia nor neutrophil degranulation during the time interval studied. Elastase plasma levels paralleled the drop in leucocyte counts and thereafter increased similarly in both groups. Lactoferrin plasma levels exhibited less increase in the treated group; however, this effect was not statistically significant. This may be due to the small number of cases studied and to difficulties in reaching effective plasma levels without side effects. PMID- 2259186 TI - Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS. AB - Sera of 1980 homo- and bisexual men who visited the Landesinstitut fur Tropenmedizin Berlin (West) between April 1983 and December 1987 were tested for HIV antibodies; 24.3% were positive. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite. There was a sexual partner with known positive HIV-antibody status or AIDS in 33.9%, and in 32.4% there was a history of sexual activity in the USA. In the year before the test, 18.8% had had more than 50 partners. All these behavioral characteristics were found to be significantly correlated to HIV antibodies. We noted a substantial reduction of high-risk behavior from 1983 to 1987. The most important behavioral factor for HIV infection in 1983 and 1984 was sexual activity in the USA, and from 1984 to 1987, the numbers of lifetime partners. Persons infected with HIV were significantly more often carriers of antibodies against HAV, HBV, CMV, EBV, and syphilis. Prevalence of antibodies against HIV, HAV, HBV, and syphilis increased with age, duration of homosexual practice, and the number of partners. Overall crude prevalence rates of HIV antibodies, anti-HBc, anti-HAV, and antibodies to syphilis declined during the observation period. Clinical findings such as fever, oral lesions, and lymphadenopathy syndrome (LAS) were found to be highly indicative of HIV infection. Lower hemoglobin values, a reduced white cell count, and hyperimmunoglobulinemia were significantly more frequent in subjects with HIV antibodies. PMID- 2259187 TI - Infective endocarditis at a hospital of the University of Kiel, 1958-1987. AB - The clinical courses of 214 patients with infective endocarditis treated between 1958 and 1987 at the First Medical Hospital of the University of Kiel (FRG) were analyzed retrospectively. A decrease in the incidence of endocarditis occurred during the 30-year observation period. The mean age of patients was 48 years, and men were more frequently affected than women. In the course of the investigation, a rise in isolated aortic valve disease was noted, whereas the number of patients with isolated involvement of the mitral valve and combined mitral-aortic valvular defects declined. Streptococci (57%) were the most frequent pathogens isolated; as opposed to their increase, the percentages of Staphylococcus aureus and enterococci decreased. Otolaryngological, dentogenic and urogenital diseases were most frequently held to be responsible for the development of infective endocarditis. Prior cardiosurgical interventions became increasingly significant as a cause of the disease. In this connection, a rising percentage of endocarditis cases was linked with prosthetically replaced heart valves. Complications and concomitant symptoms of endocarditis included the development of heart failure, cerebral embolism and encephalitis, splenomegaly, and renal inflammation. Finally, the marked decrease in mortality contrasted with a simultaneous rise in the number of endocarditis cases achieving full recovery. PMID- 2259189 TI - Assessment of the short child. PMID- 2259188 TI - [Pseudohypoparathyroidism and adrenal cortex insufficiency. A case of multiple endocrinopathy due to peripheral hormone resistance]. AB - Since his childhood a now 31-year-old male showed typical symptoms of parathyroid hormone deficiency with hypocalcemia and hyperphosphatemia. We found a target organ resistance to parathyroid hormone and diagnosed pseudohypoparathyroidism. In addition adrenal insufficiency with hypocortisolism was seen. Both hormone systems act by stimulating adenylate cyclase. A defective receptor-adenylate cyclase complex may cause this--for the first time described--combination of endocrine insufficiency. PMID- 2259190 TI - Head banging. AB - Head banging is the rhythmic movement of the head against a solid object and is marked by an almost compulsive repetitiveness. The reported incidence in childhood varies from 5 to 15%. The male to female ratio is approximately 3 or 4 males to each female. While the exact etiology is unknown, the suggested etiologies include: an integral part of normal development, a kinesthetic drive, a tension releasing maneuver, an attention-seeking device, a response to restricted activity, a consequence of emotional deprivation, and a response to various acute illnesses. The onset is usually in the latter half of the first year of life and generally ends spontaneously by four years of age. Head banging generally occurs before normal sleep. The duration may vary from a few minutes to an hour. The frontal-parietal region of the head is the most frequently struck. Although head banging appears alarming, the child seldom inflicts significant damage to the head. The physical examination in children who are head bangers is usually normal. Laboratory investigations are generally not indicated. The appropriate treatment of head banging is to offer the parents a supportive and reassuring explanation that brain damage is unlikely and that the child will outgrow the problem. PMID- 2259191 TI - Minimal change nephrotic syndrome of childhood: current concepts in management. PMID- 2259192 TI - Prenatal diagnosis of alpha-thalassaemia by analysis of enzymatically amplified DNA sequences. AB - A new method using enzymatically amplified DNA sequences for the prenatal diagnosis of alpha-thalassaemia was evaluated. DNA from a foetus at risk for alpha(0)-thalassaemia was analysed to detect the presence of alpha-globin genes. The procedure involved amplification of a 136-base-pair (bp) region of the alpha globin gene complex between the psi alpha and alpha 2 region. Amplification was performed using a pair of oligonucleotide primers and a heat stable DNA polymerase which allowed repeated cycles of DNA synthesis at 72 degrees C. A 136 bp product was detected by gel electrophoresis indicating the foetus was not positive for Bart's hydrops foetalis. The result was confirmed using the gene mapping technique. Prenatal diagnosis of alpha-thalassaemia by DNA amplification offers two advantages over the gene mapping technique since radionucleotides are not used and results can be obtained in 3 days. PMID- 2259193 TI - Acute renal failure in Reye's syndrome. AB - From 1979 to 1985, 8 children with clinical and biochemical features of Reye's Syndrome developed acute renal failure. Within the same period, a total of 28 cases of Reye's Syndrome were admitted to the Paediatric Units of Singapore General Hospital. Six of them were females and 2 were males. The mean age at presentation was 28.4 months and the range was between 9 months to 47 months. Four of them died eventually. There appeared to be a correlation between the eventual outcome and severity of renal failure and neurological state of admission. PMID- 2259194 TI - Rhabdomyolysis-induced acute renal failure in a child: a case report. AB - Rhabdomyolysis-induced acute renal failure is rare in a child. In this paper, we describe a young girl with this condition who unfortunately succumbed to adult respiratory distress syndrome. Renal biopsy confirmed the presence of tubular myoglobin casts and acute tubular necrosis but no cause for the rhabdomyolysis could be documented. PMID- 2259195 TI - A child with Henoch-Schonlein nephritis and selective proteinuria--case report. AB - In this paper, we describe a child with Henoch-Schonlein nephritis presenting with nephrotic syndrome and selective proteinuria. Renal biopsy showed ISKDC Class IIIA nephritis. He responded to steroid treatment and is currently well. The significance of renal involvement in Henoch-Schonlein Purpura is discussed. PMID- 2259196 TI - Charge association. A case report and short annotation. AB - A premature female infant was noted to have an unusual combination of abnormalities, consistent with the CHARGE ASSOCIATION. 1. Left (L) choanal stenosis 2. Fallot's Tetralogy 3. Esophageal atresia with distal TOF (Tracheo Oesophageal Fistula) 4. Duodenal stenosis 5. Annular pancreas with ectopic pancreatic tissue in the proximal jejunum. Baby had surgery for the gastrointestinal tract abnormalities. She lived for only 19 days. PMID- 2259197 TI - Effective management of long Q-T syndrome with amiodarone. AB - It is well known that episodic loss of consciousness and convulsions may have a cardiac rather than a cerebral origin (1). We report a case where these episodes were caused by recurrent ventricular tachycardia/ventricular fibrillation secondary to idiopathic long QT syndrome which was effectively treated with amiodarone. PMID- 2259198 TI - Pattern recognition of the secondary structure of proteins (alpha-helix and beta structure). AB - In this paper, an algorithm for the pattern recognition of secondary structure of proteins is proposed. The procedure simultaneously evaluates the contribution of all the residues of a given peptide to its conformation. By means of the algorithm it is possible to select from a universe of well known proteins the most representative alpha-helix and beta-structure peptides, and to use these peptides, as screening matrices to define the unknown structure of any peptide. PMID- 2259199 TI - The theory of sliding filament models for muscle contraction. II. Biochemically based models of the contraction cycle. AB - A seven-state sliding filament model is proposed which differs from the model of Eisenberg & Greene. It is based on a simplified version of the in-vitro contraction cycle of Stein et al., and also has some desirable dynamical features of the empirical three-state model of Nishiyama & Murase. Appropriate x dependences for all reaction rates are derived from the transition-state theory. The seventh-state is assumed to be a high-tension intermediate of A.M.ATP, from which direct but x-dependent dissociation can occur. If the final A.M.ATP state has a sufficiently lower tension than that of A.M.ADP.Pi, then the dominant escape path from the intermediate state is shown to be direct dissociation of the actin-myosin bond. This leads to an approximate five-state model for active and relaxed muscle in which A.M and the final A.M.ATP state are omitted. PMID- 2259200 TI - An application of membrane theory to tip morphogenesis in Acetabularia. AB - Focusing our attention on the cell wall and the plasmalemma (i.e. the cell membrane), we seek to show that the initiation of the regenerative, growing tip in the unicellular marine alga Acetabularia mediterranea, can be predicted using the techniques of thin-shell and elasticity theory. We build upon and extend the work of Goodwin & Trainor (1985, J. theor. Biol. 117, 79-106), Trainor & Goodwin (1986, Physica D. 21D, 137-145) and Briere & Goodwin (1988, J. theor. Biol. 131, 461-475) where the attention was focused on the calcium-regulated strain and stress fields of the cortical cytoplasm. Finally, we attempt to model the subsequent tip growth using a moving-boundary formulation, with cytosolic free calcium concentration and turgor pressure being the two variables responsible for the growth. PMID- 2259201 TI - Mathematical representation with graphic reconstruction on a microcomputer for an arterial tree. AB - The branching arterial tree is considered as a collection of numerous points and lines. When treated with vertex analysis, it can be expressed with a new mathematical representation, and graphical reconstruction can be carried out on a microcomputer. This new method is useful for recording an arterial tree precisely on anatomical books or comparing arteries under hypertension with those under normotension in order that the early morphological changes of hypertensive vascular disease can be revealed. PMID- 2259202 TI - Usefulness of information in bistable system and Dyson model for the origin of metabolism. AB - Useful or meaningful information for the transition between disordered and ordered states occurring in a chemical system, which organizes itself out of molecular chaos, is stochastically discussed from the viewpoint of dynamical system theory. To make the discussion perspicuous it is helpful to assume that the time evolution of the chemical system proceeds by a univariate, bistable one step process of birth-and-death type. The model for the evolution of primordial metabolism proposed by Dyson is a bistable system, and hence this model answers the purpose of illustrating the usefulness of information. PMID- 2259203 TI - Impulse patterning and relaxational propagation in excitable media. AB - Wavetrains of impulses in homogeneous excitable media relax during propagation toward constant-speed patterns. Here we present a study of this relaxation process. Starting with the basic reaction-diffusion or cable equations, we derive kinematics for the trajectories of widely spaced impulses in the form of ordinary differential equations for the set of times at which impulses arrive at a given point in space. Stability criteria derived from these equations allow us to determine the possible asymptotic forms of propagating trains. When the recovery after excitation is monotonic, only one stable train exists for a given propagation speed. In the case of an oscillatory recovery, however, many stable trains are possible. This essential difference between monotonic and oscillatory recoveries manifests itself in qualitatively distinct relaxational behaviors. PMID- 2259204 TI - On the two-compartment model for estimating the rate and extent of feed degradation in the rumen. AB - An analysis of the compartmental scheme used to determine the rate and extent of ruminal degradation of feeds is presented. Attention is given to the kinetic representation of the degradation of the potentially degradable fraction. Changing the kinetic order of the rate, and introducing indigestible substrate inhibition and microbial activity into its representation, are investigated. This leads to response functions such as the Gompertz and logistic for describing the cumulative disappearance of potentially degradable substrate during in-sacco and in-vitro incubation. PMID- 2259205 TI - A two-channel hypothesis for regulation of cell division and differentiation. AB - We propose the hypothesis that extracellular regulation of cell division and differentiation acts through just two communications channels. These channels consist of a series of redundant components: extracellular messenger hormones; these hormones' receptors; cytoplasmic proteins activated by the hormone-receptor complex; and trans-activating nuclear regulatory proteins. One channel, here labeled "D" ("differentiate"), includes transforming growth factor-beta as one of its hormones; the other, labeled "G" ("growth") includes epidermal growth factor. We postulate that signal reception occurs as a result of competition between different actuating proteins for equilibrium-controlled binding to critical DNA sites. Stem cells commit to mitosis when some high proportion of critical sites is occupied by actuating proteins of the G class, and to terminal differentiation when a high proportion is occupied by "D" actuators. Intermediate occupancy can either lead to division into one differentiated and one stem cell, or to maintenance of cells in the reference state, quiescence. Equilibrium control of binding implies that critical site occupancy will be proportional to the relative concentrations of "D" and "G" actuating proteins in the nuclear fluid. These concentrations depend on the external hormone concentrations, the numbers of receptors on the cell membrane, and the coefficients of the rate-determining steps between internalization of the hormone-receptor complexes and activation of the actuating proteins. All of these quantities can be affected by various factors, including endocrine hormones. This model is consistent with most reported behavior of various growth factors, interferons, etc, toward a variety of cells in culture. It predicts that under otherwise constant conditions, high relative concentrations of a D-hormone (e.g. transforming growth factor-beta) will induce commitment to terminal differentiation, while high relative concentrations of a "G" hormone (e.g. epidermal growth factor) will induce mitosis. We have seen no report of an experiment which adequately tests this prediction. The model implies that cancer causing mutations are those which increase the relative intensity of the "G" signal; this can occur via changes in components of either channel. Such mutant cells should be both more likely to divide and less likely to differentiate than normal stem cells. Conversely, mutations which increase relative sensitivity to the "D" signal during embryonal development can lead to premature differentiation, cessation of growth, and structural abnormalities (terata). PMID- 2259206 TI - Dynamic information in uncertain and changing worlds. AB - A general theory for information processing by organisms living in uncertain and changing worlds is developed. The three fundamental properties of the theory are: (i) the use of a memory parameter that allows the organism to forget the more distant past, (ii) a succinct representation of encounters and information and (iii) flexibility in the estimates of parameters by including the uncertainty in these estimates in a consistent manner. The theory is developed using Bayesian methods (but can also be applied to maximum likelihood estimation) and is applied to the encounter models standardly used in ecology (Poisson, binomial, and negative binomial). Two applications are discussed: (i) patch selection and the matching rule and (ii) superparasitism by a parasitoid. PMID- 2259207 TI - Transcription initiation and nuclease-sensitive sites upstream of the epsilon globin gene in K562 cells are related to poly (dA).poly (dT) sequences. AB - Previous studies have documented transcription initiation sites and nuclease hypersensitive sites upstream of the epsilon-globin canonical cap site in K562 cells. The upstream transcription initiation sites coincide with some of the nuclease hypersensitive sites. Comparison of the positions of the upstream transcription initiation and the nuclease hypersensitive sites with the nucleotide base order shows that these upstream sites fall significantly closer to poly (dA).poly (dT) tracts than can reasonably be accounted for by chance. It is concluded that these sites are related to the occurrence of poly (dA).poly (dT) tracts of at least five base pairs. Other studies have related some particular functional properties to poly (dA).poly (dT) tracts. Additionally, poly (dA).poly (dT) tracts have been shown to have unusual physical characteristics and to produce an intrinsic bending of the DNA molecules in which they are located. This study indicates that poly (dA).poly (dT) tracts can provide access to DNA for RNA polymerases and induce a DNA conformation recognized by DNase I or S1 nuclease. PMID- 2259208 TI - Molecular friction in an actomyosin molecular machine. AB - In muscle contraction, it has been widely recognized that a binding state exists between myosin and actin in the presence of Mg-ATP. To estimate the magnitude of binding strength, I introduce a concept of frictional phenomena which occurs between two sliding bodies in contact each other. In such cases, the sliding speed can be formulated as a function of the actin-myosin bond strength. In order to validate this, the present theory is applied for the two movement assay systems with no external load; one movement assay of Phalloidin Rhodamine bound F actin on a myosin coated hydrophobic cover glass and another assay of myosin coated beads along actin cables of Nitella. If a coefficient of 0.005 is applied to the kinetic friction, 1pN for the sliding force per cross-bridge and 10 microns sec-1 for the sliding speed, it is found that the bond strength between actin and one myosin head is about 200 pN in the contracting state. PMID- 2259209 TI - Velocity-induced modifications in the crossbridge and/or the actin filament behavior during shortening of muscle fibers. AB - It has been shown experimentally that, in single muscle fibers, the force velocity relation is more complicated than usually found (Edman, 1988a. Adv. expl. Med. Biol. 226, 643-652; 1988b, J. Physiol., Lond. 404, 301-321). In particular, there is a discontinuity in this relation for high loads (P/P0 greater than or equal to 0.8), i.e. for low velocities of shortening. Here the mathematical approach of the crossbridge behavior is used, independent of their mechanical role(s). This approach has been already presented in previous papers (Morel, 1984a,b, Prog. Biophys. molec. Biol. 44, 47-96, and references therein). It was found that, at P/P0 approximately 0.80, the force-velocity relation presents a reversal of curvature, which was compatible with the previous results obtained by Edman et al. (1976, Acta Physiol. Scand. 98, 143-156). However, by using extremely elegant techniques, Edman (1988a,b) found a different relation. Here, this problem is studied and it is shown that it is possible to fit the new relationship, provided it is assumed that shortening per se modifies the mechanical properties of the crossbridges and/or the actin filaments. For instance, the interval of attachment of a crossbridge increases with V and the constants of attachment f and detachment g decrease with V. Moreover, it is shown that this approach can predict the approximate constancy of the proportion of crossbridges attached to actin, irrespective of V. This is an old result presented by Podolsky et al. (1976, Proc. natn. Acad. Sci. U.S.A. 73, 813-817). This proportion is approximately 0.97.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259210 TI - The effect of temperature on photoperiodic induction of diapause in insects and mites: a model for the photoperiodic "counter". AB - Existing models for the accumulation of photoperiodic information (the photoperiodic "counter") cannot explain satisfactorily the various effects of temperature on diapause induction in insects and mites, nor the observation that in several insect species the so-called "required day number" has a high degree of temperature compensation. In the model presented in this paper the effect of temperature has been incorporated in such a way that both the rate of increase of the "induction sum" (or "diapause titre") and the level of the "minimally required induction sum" (or "threshold level") are temperature dependent. The proposed model is in accordance with observed temperature effects, and gives an explanation for a temperature-compensated "required day number". PMID- 2259211 TI - Computer experiments on the evolution of sex: the haploid case. AB - We have conducted a set of computer experiments that investigate the conditions under which sexual reproduction can evolve. In these experiments, haploid genomes are treated as integer strings able to undergo mutation and, in the case of sexual strings, recombination, with string sequence (the genotype) determining fitness. Our results indicate that the likelihood of a rare sexual mutant spreading through an otherwise asexual population is small when sexual reproduction entails the classical two-fold cost of males. However, our results indicate that when mutation rates are not excessively high, sexual reproduction constitutes a more efficient fitness optimization algorithm, allowing a sexual population to adapt more quickly to its environment than an asexual population. PMID- 2259212 TI - Analysis of a model for minichromosome segregation in Escherichia coli. AB - The present article contains a theoretical, quantitative analysis of the implications of the Helmstetter-Leonard model (1987, J. molec. Biol. 197, 195 204.) for the segregation of chromosomal DNA in Escherichia coli, on the expected copy-number distribution of minichromosomes in a culture in steady-state exponential growth. According to the model, two determinants are involved in the mechanism of chromosome segregation: a partition system that assures the equal allotment of chromosomes between daughter cells at cell division, and a locus within the minimal oriC region that specifies the attachment site of the chromosomes to the cell envelope at initiation of replication. There are many parameters that must be taken into account in such a study, and since some of them are probabilistic in nature, a strictly analytical approach is not feasible and we had to resort to computer simulation. A wide range of parameter values was tested, in all combinations. The minichromosome copy-number distributions obtained all had a prominent mode equal to the number of oriC binding sites and their main features were determined essentially by that and very little by any of the other parameters of the model. In order to avoid the unrealistic situation in which this one feature completely dominates the results, the original model was modified so that each individual minichromosome is no longer required to replicate during every cell generation, by introducing a limit to the number of unsuccessful attempts to locate a suitable binding site. The copy-number distributions predicted by this version of the model are quantitatively and qualitatively very different and depend on all the components of the model. The simulation results are sufficiently well-behaved to allow consideration as to whether a particular empirical minichromosome copy-number distribution--when such data become available--could in fact be governed by the proposed model; it may even be possible to get a rough estimate for the different parameters involved. PMID- 2259213 TI - Chaotic dynamics in an ionic model of the propagated cardiac action potential. AB - We simulate the effect of periodic stimulation on a strand of ventricular muscle by numerically integrating the one-dimensional cable equation using the Beeler Reuter model to represent the transmembrane currents. As stimulation frequency is increased, the rhythms of synchronization [1:1----2:2----2:1----4:2---- irregular ---3:1----6:2----irregular----4:1----8:2----...----1:0] are successively encountered. We show that this sequence of rhythms can be accounted for by considering the response of the strand to premature stimulation. This involves deriving a one-dimensional finite-difference equation or "map" from the response to premature stimulation, and then iterating this map to predict the response to periodic stimulation. There is good quantitative agreement between the results of iteration of the map and the results of the numerical integration of the cable equation. Calculation of the Lyapunov exponent of the map yields a positive value, indicating sensitive dependence on initial conditions ("chaos"), at stimulation frequencies where irregular rhythms are seen in the corresponding numerical cable simulations. The chaotic dynamics occurs via a previously undescribed route, following two period-doubling bifurcations. Bistability (the presence of two different synchronization rhythms at a fixed stimulation frequency) is present both in the simulations and the map. Thus, we have been able to directly reduce consideration of the dynamics of a partial differential equation (which is of infinite dimension) to that of a one-dimensional map, incidentally demonstrating that concepts from the field of non-linear dynamics- such as period-doubling bifurcations, bistability, and chaotic dynamics--can account for the phenomena seen in numerical simulations of the cable equation. Finally, we sketch out how the one-dimensional description can be extended, and point out some implications of our work for the generation of malignant ventricular arrhythmias. PMID- 2259214 TI - Records of usage or assays in Phyllanthus (Euphorbiaceae). I. Subgenera Isocladus, Kirganelia, Cicca and Emblica. AB - References to either indigenous uses or the results of controlled assays are numerous for species of Phyllanthus (Euphorbiaceae). These citations have been arranged by subgenus, section, subsection and species and will be published as three separate papers, followed by a paper discussing the apparent clustering of some uses or effects within taxa. This paper, the first of the series, covers the subgenera Isocladus, Kirganelia, Cicca and Emblica. PMID- 2259215 TI - Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. AB - Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4 were able to double the islet number and beta cell number. This herbal therapy appears to bring about blood glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the endocrine pancreas. PMID- 2259216 TI - Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin dependent diabetes mellitus. AB - GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day) to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin requirements came down together with fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained higher than controls. IDDM patients on insulin therapy only showed no significant reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12 months. GS4 therapy appears to enhance endogenous insulin, possibly by regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus. PMID- 2259217 TI - Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin dependent diabetes mellitus patients. AB - The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral anti-hyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to the conventional oral drugs. During GS4 supplementation, the patients showed a significant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone. These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after GS4 supplementation. PMID- 2259219 TI - Induction of neutrophil accumulation by red ginseng. PMID- 2259218 TI - Effects of Morinda lucida leaf extract on Trypanosoma brucei brucei infection in mice. AB - The dried leaves of Morinda lucida were extracted with 50% methanol and the extract was recovered in a 9.7% w/w yield. Acute toxicity tests were performed in mice and the intraperitoneal LD50 of the extract was 2000 mg/kg. The extract induced purgation in mice from the first hour after oral administration and reached its peak between the third and fourth hour. The purgation was not dose dependent. M. lucida leaf extract i.p. significantly suppressed the level of parasitemia after Trypanosoma brucei infection in mice. Suppression of existing parasitemia appeared dose-dependent with 1000 mg/kg i.p. producing the maximum effect. The best trypanocidal activity was obtained when treatment with M. lucida extract commenced simultaneously with trypanosome inoculation. PMID- 2259220 TI - Is remission in acute myelogenous leukemia re-establishing preleukemia? PMID- 2259221 TI - Antiviral effect of zidovudine in the experimental model of adult T cell leukemia in rabbits. AB - The antiviral effect of zidovudine was examined in an experimental model of adult T cell leukemia in rabbits. AZT retarded the growth of HTLV-I-transformed rabbit cell line (F647a) and inhibited the transformation of normal peripheral blood lymphocytes in co-culture with the cell line. Inhibition of the transformation was achieved at a much lower concentration of AZT than the suppression of cell growth. Seven newborn F1 hybrids were inoculated intraperitoneally with 1 x 10(7) F647a cells and then were given AZT intraperitoneally, either at a high dose (300 mg/kg/day) or a low dose (30 mg/kg/day) for three weeks. Four newborn animals similarly given F647a cells were left untreated as a control. Examinations carried out three weeks after cell inoculation revealed the following: the HTLV-I provirus was not or hardly detected by the polymerase chain reaction in the peripheral blood lymphocytes of animals given a high dose of AZT, whereas the provirus was detected in all untreated control animals as well as in two animals given a low dose of AZT. In addition, lymphocytic infiltration was not observed in the major organs of the former animals, but was observed in those of the latter animals. These indicate the effectiveness of AZT administration for the prevention of HTLV-I infection and ATL-like disease in rabbits. PMID- 2259222 TI - Immunophenotype of blast cells in acute myelofibrosis. AB - The immunophenotype of peripheral blood blast cells from six patients with acute myelofibrosis was studied using a panel of monoclonal antibodies directed against granulocytic, erythroid, megakaryocytic and lymphoid antigenic determinants. In all patients most of the blast cells were labeled with anti-HLA-DR and with the early myelomonocytic antibodies My7 (CD13), My9 (CD33) and B1-3C5 (CD34) (3/3). In three cases, platelet antibodies Edu3 (CD41) and GPIIIa (CD61) reacted with about 30% of blast cells. TdT was positive in two out of six samples studied. Lymphoid markers T3 (CD3), Leu9 (CD7), J5 (CD10), B4 (CD19) and B1 (CD20) were negative in all cases. These results suggest that blast cells are mainly of immature myelocytic origin. However, the coexistence of megakaryoblasts cannot be ruled out in the cases with a proportion of cells that are positive with Edu3 and GPIIIa antibodies. PMID- 2259223 TI - Quantitative variations in A, B, Ht1 and Ht2 antigens on erythrocytes in leukemia and lymphoma. AB - Using an immunoradiometric assay, A, B, Ht1 and Ht2 antigens on erythrocyte membranes were quantitated in 192 leukemia and 23 lymphoma patients. A and B antigens were reduced in 37% and 50% of leukemia cases respectively. A wide range of antigenic reduction was observed for A antigen, while B antigenic reduction was generally 16-20%. Passive absorption of Ht1 antigen from plasma onto erythrocytes was greater in leukemic compared to normal subjects. Among patients with reduced A and B antigens, 27% had increased and 37% decreased Ht2 antigens. Incidence of reduction in antigens was significantly higher (p less than 0.001) in untreated compared to treated patients. PMID- 2259224 TI - Control of actin conformation in AML myeloblasts: the effects of bryostatin and TPA. AB - Protein kinase C (PKC), an enzyme involved in signal transduction, is the receptor for both the tumor-promoting phorbol esters and the anti-neoplastic bryostatins. In many cells, phorbol esters and bryostatins cause similar effects; we have found that both agents increase actin polymerization in neutrophils. In some cells, however, the two agents result in different cell processes; we have found consistently different effects of these agents on actin conformation in myeloblasts obtained from leukemic patients. The patients tested all had increases in F-actin in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) and most had decreases in F-actin in response to bryostatin. The data suggests that leukemic myeloblasts have a different cytoskeletal response to a tumor promoter and an antineoplastic agent despite their common receptor. PMID- 2259225 TI - Lithium enhances the proliferation of HL-60 promyelocytic leukemia cells. AB - The effects of lithium, an agent used in the treatment of manic depression and to attenuate myelosuppression during chemotherapy, on HL-60 promyelocytic leukemia cells were investigated. By monitoring cell growth at varying concentrations (0 50 mM), as well as by following cell proliferation over 8 days, it was established that lithium stimulates HL-60 proliferation within a very narrow concentration range. Enhancement of growth was optimal at 5 mM, whereas concentrations above 10 mM were toxic. Time course studies revealed that the greatest increase in cell number occurred after 5-6 days in the presence of lithium. This was preceded by DNA synthesis reaching a maximum after 1-2 days. Viability of the cells decreased gradually after 3 days with 5 mM, but not with 2.5 mM. We suggest that HL-60 cells are a suitable model to further investigate possible mitogenic and cytotoxic effects of lithium in vitro. PMID- 2259226 TI - Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial. AB - In a randomized trial, 299 evaluable patients with acute myelogenous leukemia, age greater than or equal to 51, were initially randomized to cytosine arabinoside, 100 mg/m2/day, by continuous intravenous infusion for seven days, plus either daunorubicin 45 mg/m2/day x 3 (DA), or m-AMSA 200 mg/m2/day x 3 days (MA). Complete remission (CR) rates were not significantly different, 47% for DA and 42% for MA. Toxicities were similar except that severe hepatic toxicity, serum bilirubin greater than or equal to 7 mg/dl, was more frequent in patients receiving MA (10%) than in patients receiving DA (4%), p less than 0.05. Deaths during induction were significantly more frequent in patients receiving MA (38%) than in patients receiving DA (25%), p = 0.018. Patients achieving a CR received thioguanine, cytosine arabinoside, and daunorubicin (TAD) for three cycles as consolidation. Among evaluable patients, 82/102 (80%) stayed in CR during these three cycles. Patients were then randomized to either no maintenance or to DA every 13 weeks x 4 cycles, at a dose slightly lower than used for induction. Remission duration was similar for the two maintenance programs, 10.7 months for no maintenance and 8.5 months for DA. The percentage of patients evaluable for maintenance achieving three year relapse-free survival was similar for the two maintenance programs, 28% for no maintenance and 21% for DA. However, overall survival was significantly greater (40 vs 12 months, p = 0.007) for patients receiving no maintenance therapy, due to greater survival after recurrence in these patients. At each phase of the study there were substantial numbers of non evaluable cases, often due to incomplete evaluation of remission status. Of the 379 patients initially entered into the trial, 35% obtained a complete remission. Of all the patients who achieved a complete remission, 61% were both evaluable and in remission upon completion of the maintenance phase. Of these patients who completed the maintenance phase in remission, 15% were relapse free survivors three years following initiation of maintenance therapy. Overall, only 3.2% of patients who entered the trial (35% x 61% x 15%) were continuous relapse-free survivors three years into the maintenance phase. PMID- 2259227 TI - DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b. AB - Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls. PMID- 2259228 TI - Expression of human myeloid cell nuclear differentiation antigen (MNDA) in acute leukemias. AB - Human myeloid cell nuclear differentiating antigen (MNDA) is a Mr 55,000 non histone basic nuclear protein expressed in myeloid leukemia cell lines that are at late stages of differentiation (HL-60 and U937) and in normal granulocytes and monocytes, but is not present in lymphoid cells or in other human cells and tissues tested. Affinity purified monospecific polyclonal antibodies and rat monoclonal antibodies have been developed for the immunocytochemical detection of MNDA. Using these antibodies, we surveyed 21 cases of acute leukemia classified by French-American-British (FAB) Group criteria, two cases of biphenotypic acute leukemia and one case of blast crisis of chronic granulocytic leukemia for the presence of MNDA. The most intense staining reactions were present in the nuclei of two cases of acute promyelocytic (FAB M3) leukemia. MNDA was not detected in three of five cases of acute myeloblastic leukemia without maturation (FAB M1). The remaining two cases of the M1 category showed weak to moderate staining. No staining reaction was seen in acute lymphocytic leukemia (ALL), biphenotypic leukemia or the lymphoid blast crisis of chronic granulocytic leukemia. Variable staining reactions were demonstrated in the remaining cases. These data suggest that the presence of MNDA is correlated with myeloid and monocytic differentiation in acute leukemia, being strongly expressed in M3 type, often not detected in M1 leukemia and absent in ALL. PMID- 2259229 TI - Flow cytometric studies on actin polymerization in PMN cells from chronic myeloid leukemia (CML) patients. AB - Studies in our laboratory have shown that polymorphonuclear leucocytes (PMNL) from chronic myeloid leukemia (CML) patients are defective in chemotaxis towards a synthetic peptide, n-formyl-methionyl-leucyl-phenylalanine (FMLP), during the active phases of the disease and in remission. Actin plays a major role in cellular movements and binding of chemo-attractant to cells induces polymerization of G-actin to F-actin. We have, therefore, compared polymerization of actin in FMLP stimulated PMNL from CML patients with those from normal subjects by fluorescence microscopy and flow cytometry, using F-actin specific probe, NBD-phallacidin. Our results show that binding of FMLP to normal PMNL induces rapid conversion of G-actin to F-actin followed by depolymerization to some extent. In CML PMNL, such a biphasic response is not seen. Conversion of G actin to F-actin is slower and F-actin content is significantly lower than that in normal PMNL. Moreover, organization of F-actin is different in CML PMNL as compared to that in normal PMNL. PMID- 2259230 TI - Elevated argininosuccinate synthetase activity in adult T leukemia cell lines. AB - Argininosuccinate synthetase (ASS) is a ATP-dependent and rate-limiting enzyme of the urea cycle which catalyzes L-citrulline to L-arginine in combination with argininosuccinate lyase (ASL). We demonstrate here that (a) human normal T and B lymphocytes did not express ASS activity, (b) however, three adult T leukemia (ATL) cell lines tested here exhibited significant elevation of ASS activity, and (c) ASL activity remained relatively constant in normal lymphocytes and various leukemia cell lines. These results suggest that the ASS expression of peripheral blood lymphocytes is of value as a diagnostic marker of leukemia including ATL. The implication of these results is discussed. PMID- 2259231 TI - Electrochemical detection, HPLC and in vivo monitoring in the biosciences. PMID- 2259232 TI - Electrochemical detection, HPLC and in vivo monitoring in the biosciences. A selection of papers from the 4th conference. 19-21 November 1989, Nottingham, U.K. PMID- 2259233 TI - Dopamine concentration in the cytoplasmic compartment of single neurons determined by capillary electrophoresis. AB - It has long been a goal of the biochemist to study the chemistry of single cells. This is particularly important in neuroscience, since each cell can maintain a specific function and identity. Investigations into neurotransmitter compartmentalization within the cell body of neurons should lead to an understanding of the role of the cell body in metabolism, uptake and storage of neurotransmitters. Using capillary electrophoresis, it has been possible to separate and detect attomole levels of neurotransmitter in picoliter volumes of cytoplasm withdrawn from single neurons of the pond snail, Planorbis corneus. This work demonstrates, for the first time, the direct determination of the cytoplasmic concentration of dopamine in single, intact neurons. PMID- 2259234 TI - Mesocorticolimbic dopaminergic systems and emotional states. AB - We have used the technique of in vivo voltammetry with carbon fibre electrodes to investigate further the involvement of ascending mesencephalic dopaminergic systems in emotional states in freely moving rats. In Sprague-Dawley rats, forced locomotion caused an increase in extracellular DOPAC levels in the striatum and nucleus accumbens but not in the prefrontal cortex. Immobilization (4 min) or systemic injection of the anxiogenic agent methyl-beta-carboline carboxylate enhanced extracellular DOPAC in both prefrontal cortex and nucleus accumbens but not in striatum whereas tail-pinch provoked a selective increase in this parameter in the nucleus accumbens. These data suggest that mesolimbic and mesocortical dopaminergic systems can be specifically activated by certain kinds of anxiogenic stimuli. To evaluate the relationship between emotional status and the response of mesocortical dopaminergic neurons to stress, we investigated the effects of stressful conditions on dopamine metabolism in the prefrontal cortex of 2 genetically selected lines of rats which differ drastically in their level of emotionality. Introduction of the animals into an unfamiliar environment, application of a high-intensity loud noise or immobilization were associated with an increase in extracellular cortical DOPAC levels in the hypoemotional (RHA) but not in the hyperemotional (RLA) line. These results suggest that the increase in cortical dopamine metabolism induced by stress is not connected to the emotional reaction caused by the aversive nature of the stressor but may reflect activation of cognitive processes in an attempt to cope with the stressor. PMID- 2259235 TI - Lever pressing for food reward and changes in dopamine turnover and uric acid in rat caudate and nucleus accumbens studied chronically by in vivo voltammetry. AB - The neurotransmitter dopamine (DA) is widely held to be involved in the maintenance of positively reinforced behaviour, on the basis of self-stimulation experiments and of the effects of drugs which alter DA transmission on self stimulation, and on behaviours controlled by natural reinforcers. We have used the technique of linear sweep voltammetry at chronically implanted carbon paste electrodes to demonstrate that 30-min sessions of responding on a variable interval schedule for food pellet reward increases first uric acid and then homovanillic acid (HVA, the DA metabolite) in rat caudate. Ascorbic acid levels are reduced, but at later times. We have now established that very similar responses in magnitude and timing are seen in the nucleus accumbens. Furthermore, in individual animals, the response rates, the increases in dopamine turnover, and the changes in uric acid and ascorbic acid remain stable when studied periodically over a 3 month period. Our previous results are broadly consistent with those obtained by others using indirect single-point methods (ex vivo neurochemistry) or in vivo dialysis. However, our present extended observations made possible by the use of paste electrodes (rather than fibre electrodes or dialysis probes) open the possibilities of studying the evolution of neurochemical responses during learning, and the covariation of neurochemical and behavioural effects of drugs within individual animals. PMID- 2259237 TI - The use of Doppler ultrasound in the study of fetal cardiovascular physiology. AB - Doppler velocimetry of the uteroplacental and umbilical arteries provides an opportunity for the safe, reproducible and repeatable study of these circulations and already has led to an increased knowledge of the pathophysiology of pregnancy induced hypertension and intra-uterine growth retardation. This technique, which has only recently been introduced widely into obstetrics, also permits the study of the cardiovascular effects on the fetus of maternally administered drugs. The use of Doppler for these purposes is illustrated with particular reference to intra-uterine growth retardation and the use of the antihypertensive drugs, atenolol and nifedipine. PMID- 2259236 TI - In vivo neurochemical effects of tail pinch. AB - Tail pinch in the rat gives rise to a well characterised pattern of behaviour which includes gnawing, licking and eating. We have used both in vivo voltammetry and microdialysis to monitor neurochemical changes which accompany the behavioural response to a 5-min tail pinch. Tail pinch resulted in a increase of extracellular 5-hydroxytryptamine and a smaller and more delayed increase of 5 hydroxyindole acetic acid in the hippocampus. In the striatum there was a rise of both extracellular dopamine and ascorbate. With a recently developed constant potential voltammetric technique we can continuously monitor changes in extracellular ascorbate. Using this technique we found a very rapid rise in ascorbate current during a 5-min tail pinch; the current began to decline as soon as the clip was removed. The high time resolution of the technique also allowed us to record similar ascorbate changes during a 0.5-s tail pinch. PMID- 2259238 TI - New technical and clinical aspects for cerebrovascular applications of ultrasound methods. AB - Various Doppler-ultrasound methods have been established for the evaluation of both extracranial and intracranial vascular diseases. The validity of the presently used techniques and new aspects of work in progress are demonstrated and discussed in detail because of the increasing clinical interest in detailed vascular information for prospective follow-up investigation. PMID- 2259239 TI - Amino acid measurement by high-performance liquid chromatography using electrochemical detection. AB - The measurement of amino acids by high-performance liquid chromatography has become more common in recent years. Separation can be by gradient elution of the native amino acids followed by reaction with ninhydrin or by pre-column derivatisation with ultraviolet or fluorescent detection. The use of electrochemical detection for the measurement of amino acid derivatives formed with either o-phthalaldehyde or phenylisothiocyanate is discussed. A method for the assay of amino acids in human blood serum and urine samples using phenylisothiocyanate as the derivatizing agent and electrochemical detection is described and compared to previously reported methods based on o-phthalaldehyde derivatisation. PMID- 2259240 TI - The sympathoadrenal system, obesity and hypertension: an overview. AB - Obesity-related hypertension is a clinical problem of major significance. The nature of the relationship between blood pressure and body weight has not been elucidated. Recent studies suggest that insulin (and/or insulin resistance) may be involved. An hypothesis is developed, based on the relationship between dietary intake and sympathetic activity, that attributes obesity-related hypertension to sympathetic stimulation. PMID- 2259241 TI - Effects of nutrient intake on sympathoadrenal activity and thermogenic mechanisms. AB - Ingestion of carbohydrate results in a diphasic activation of the sympathoadrenal system. One component is an insulin-mediated activation of the sympathetic nervous system (SNS). This activation is partly a haemodynamic reflex, but it may cause a weak thermogenic effect via beta 1-adrenoceptors in white adipose tissue, the liver and the heart. The second thermogenic component of carbohydrate occurs later when the blood glucose concentration decreases towards baseline levels. This elicits an increased secretion of adrenaline from the adrenal medulla, and the circulating level exceeds the physiological threshold for thermogenic effect. The target is mainly skeletal muscle where thermogenesis is stimulated via beta 2 adrenoceptors. Also the basal metabolic rate and the thermogenic responses to cold and heat exposure, mental stress and exercise, have facultative components. Inhibition of facultative thermogenesis by beta-blockers such as propranolol, diminishes the daily energy expenditure and promotes weight gain and obesity. Although thermogenesis mediated by the sympathoadrenal system accounts for only a small part of the daily energy expenditure, it is sufficient to explain the positive energy balance and weight gain reported in patients receiving treatment with beta-adrenoceptor blocking agents. PMID- 2259242 TI - 5-HT neuroendocrine responses during psychotropic drug treatment: an investigation of the effects of lithium. AB - Increasing brain 5-hydroxytryptamine (5-HT) function in humans raises plasma concentrations of prolactin, growth hormone and ACTH. Measurement of these hormonal responses provides an index of the functional activity of brain 5-HT pathways. More recent strategies have included the use of directly-acting 5-HT receptor agonists to probe the function of specific receptor subtypes; at present these studies are limited by the questionable selectivity of the agonists employed. Using 5-HT neuroendocrine testing it can be shown that lithium specifically increases the prolactin release mediated by 5-HT pathways. Further studies are needed to determine if this effect is caused by an enhanced sensitivity of post-synaptic 5-HT1A receptors. PMID- 2259243 TI - Single photon emission computed tomography (SPET) of the brain. AB - The X-Ray CT scanner and MRI imaging of the brain have changed the study of this organ, in health and in disease. To add to the detailed demonstration of anatomy, functional imaging of the human brain is now carried out by either positron emission computed tomography (PET) or by single photon emission computed tomography (SPET). PET allows for the investigation of brain blood flow, metabolism and many neuroreceptors and is well placed to study the interaction between a drug and the brain. Its clinical (patient-orientated) problem solving potential remains limited--it is too costly a methodology. SPET of the human brain is the affordable, patient-dedicated, alternative. SPET is available in hundreds of departments throughout the U.K. and the E.E.C. Significant progress has been achieved with 99mTc and or 123I-labelled radiopharmaceuticals. Flow studies can be obtained with almost as much detail as most PET flow studies, and progress is at hand with the mapping of neuroreceptor ligands. A metabolic marker for SPET studies is still missing. However flow and metabolism follow a parallel course in most clinically relevant entities (for instance in epilepsy and dementia) -- hence SPET flow maps appear as an attractive alternative to PET. SPET studies of transit (flow/volume) offer an alternative to PET studies of oxygen extraction, since these parameters appear to correlate with each other. PMID- 2259244 TI - Optimization of LC apparatus for determinations in neurochemistry with an emphasis on microdialysis samples. AB - The popularity of in vivo microdialysis sampling of low-molecular-weight substances has focused attention on improved liquid chromatography procedures for such studies. The complexity of the in vivo experiment, coupled with the complexity of LC, has discouraged some workers from developing this capability in their laboratory. Many small-volume dialysate samples are collected over hours of experiments. Proper handling of the animal (anaesthesia, temperature control, probe size and placement, choice of perfusion media) is critical. Simultaneously giving equal attention to sample collection and storage, derivatization, analysis precision, calibration for accuracy, and preventive maintenance of LC pumps, columns, and detectors is difficult for many laboratories. For reliable LC-based assays for microliter volumes of dialysates minimum human interaction with the samples is desirable. Automation strategies and selection of LC components which we have adopted are described for routine analytes such as biogenic amines, amino acids, choline/acetylcholine, and glucose. PMID- 2259245 TI - Microdialysis measurement of in vivo neuropeptide release. AB - The application of the microdialysis sampling technique for in vivo measurement of neuropeptide release is discussed. In vitro recoveries of different microdialysis membranes are described for a variety of neuropeptides (ranging from 400 to 4500 MW) as well as their dynamic potential for measuring external concentration changes. In vivo experiments illustrating the use of the technique for measuring release of oxytocin and met-enkephalin from the brain of the conscious sheep, and vasopressin in the blood of the anaesthetised rat are described. PMID- 2259246 TI - Detection of neuropeptide release in the central nervous system with antibody microprobes. AB - Antibody microprobes are glass micropipettes bearing a uniform layer of immobilized antibodies on their outer surfaces. When a microprobe is placed in the central nervous system, localized release of a ligand for the particular antibody produces binding at a localized area of the microprobe. This is detected on microprobe autoradiographs as deficits in the binding of a radiolabelled form of the ligand in which probes are incubated after withdrawal from the brain or spinal cord. An image analysis system scans autoradiographs quantitatively. Experiments are best done under near sterile conditions as peptides and proteases occur in inflammatory exudates. PMID- 2259247 TI - Brain microdialysis studies on the control of dopamine release and metabolism in vivo. AB - This paper studies the actions of drugs known to release dopamine from brain tissue. Most of the theoretical background to this work has been developed in experiments on slices of brain in vitro but using in vivo microdialysis we have elaborated and extended the ideas from the in vitro experiments and been able to make a direct comparison of the mechanism of action and source of dopamine released by 5 different manipulations. The mode of action of tyramine, amphetamine, veratrine, ouabain and potassium is discussed in the light of the computer model of the nerve terminal published by Justice et al. (1988). The data may lend themselves to such an interpretation, but they could be compatible with several other models. PMID- 2259248 TI - Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor. AB - 5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype are localized on serotoninergic cells and dendrites in the raphe nuclei of the brain stem and are believed to regulate synaptic 5-HT release through an inhibitory influence on serotoninergic impulse flow. The effects of 5-HT1A agonists on 5-HT release can, therefore, only be detected by measurement of 5-HT release from intact serotoninergic neurones. Here we review the evidence that the microdialysis technique, when applied to the anaesthetized rat, is able to detect extracellular 5-HT in the brain which derives from serotoninergic neurones and changes in accordance with serotoninergic neuronal activity. We have observed that a range of 5-HT1A agonists, including 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT), inhibit 5-HT release in hippocampus, most probably by acting on somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. The inhibitory action of 8-OH-DPAT and several other selective 5-HT1A receptor active drugs on 5 HT release is sensitive to pindolol, further supporting the idea that the 5-HT receptor being measured is of the 5-HT1 subtype. Two drugs, BMY 7378 and NAN-190, which show 5-HT1A antagonist properties in certain models, reduce 5-HT release indicating that they have mixed agonist/antagonist actions at the 5-HT1A receptor. Our data indicate that measurement of 5-HT release in rat brain using the microdialysis technique may be a useful method to probe the pharmacology of the 5-HT1A autoreceptor in vivo. PMID- 2259249 TI - An in vivo microdialysis characterization of extracellular dopamine and GABA in dorsolateral striatum of awake freely moving and halothane anaesthetised rats. AB - This study describes the results of a systematic characterization of extracellular dopamine (DA) and gamma-aminobutyric acid (GABA) recovered from dorsolateral striatum using in vivo microdialysis in rats following acute (2.5 h) and chronic (1 day, 2 day and 4 day) implantation of the probe. The voltage and calcium dependence of DA and GABA overflow was characterised by perfusion with the sodium channel blocker tetrodotoxin (TTX 10-6M) and with Ca2(+)-free Ringers perfusion medium. In addition, the effect of halothane anaesthesia on the responsiveness of these neurotransmitter substances to TTX and Ca2(+)-free perfusion medium was investigated. Perfusion with TTX decreased basal DA levels by at least 60% in all groups. The TTX-induced decrease was most profound in halothane-anaesthetised rats, 24 h after implantation of the probe. Responsiveness of GABA to TTX infusion was different between the groups. In acutely implanted halothane-anaesthetised rats basal GABA levels were unaltered by perfusion with TTX while in the remaining groups at least a 35% reduction was observed. In awake rats 2 days following implantation of the probe removal and replacement of the Ca2+ from the perfusion medium resulted in a reversible reduction of basal DA by 87%. In addition, basal GABA levels were decreased by 52%. This decrease was delayed and was not reversed 1.5 h after the Ca2(+)-free perfusion medium was replaced with normal perfusion medium although basal GABA levels returned to pre-experimental levels by the following day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259250 TI - Aging and endothelial barrier function in culture: effects of chronic exposure to fatty acid hydroperoxides and vitamin E. AB - As the endothelium ages it may become more susceptible to damage by atherogenic plasma components such as toxic lipid oxidation products. Vitamin E (vit E) might prove to be anti-atherogenic by reducing oxidative injury. This study investigated the effects of age and chronic exposure to fatty acid hydroperoxides (OFA) and/or vit E on endothelial barrier function (EBF) and cell growth characteristics. Chronic exposure to 5 microM OFA for 40 passages resulted in an age-related decrease in EBF, while supplementation of OFA-treated cultures with 25 microM vit E protected against the OFA-mediated decrease in EBF, independent of cell age. Vit E treatment alone had no significant effect on EBF relative to control cultures. No changes in growth characteristics, i.e., total DNA or protein per culture, were noted, regardless of treatment, although total DNA per culture decreased with increasing culture passage. These results suggest that chronic oxidative stress decreases EBF, predisposing the artery to infiltration by blood components and subsequent atherogenesis and that vit E delays cumulative changes in EBF related to chronic OFA exposure. PMID- 2259251 TI - Transplantation of pituitary grafts fail to restore immune function and to reconstitute the thymus glands of aged mice. AB - There is evidence to indicate that the neuroendocrine and immune systems can interact. Thus, neuroendocrine hormones can modulate a variety of immune functions and there have been attempts to manipulate the neuroendocrine system of aged animals to enhance immune function. We have previously shown that the transplantation of a syngeneic pituitary gland under the kidney capsule of young adult mice elevates serum prolactin and enhances immune responsiveness. In the present study pituitary glands were transplanted under the kidney capsule of 22 month-old mice to determine if this maneuver can enhance a number of immunologic parameters. The results demonstrate that aged animals bearing transplanted pituitary grafts for 10 days did not exhibit any enhancement in their primary antibody response to sheep red blood cells, splenic T or B-cell mitogen responsiveness or restoration of thymic architecture. When these immunologic assessments are performed on animals bearing pituitary grafts for 28 days, the IgM and IgG primary antibody responses and splenic T-cell responsiveness are enhanced but repopulation of the thymus still does not occur. Importantly, this enhancement does not restore immunocompetence to levels observed in young mice. PMID- 2259252 TI - Effects of age on myosin and creatine kinase isoforms in left ventricles of Fischer 344 rats. AB - Left ventricles of hearts from male Fischer 344 rats of 2, 8 and 23 months of age were analyzed to determine if aging results in significant alterations in the isoform distribution of myosin and creatine kinase protein and mRNAs. Left ventricles of maturing (2-month) rats contained almost exclusively alpha-myosin heavy chain (MHC) mRNA and protein. In adults (8 months) there was a 5-fold increase in beta-MHC (fetal isoform) and an approximate 10% decrease in alpha-MHC mRNA levels, relative to 2 months. By 23 months (senescence), beta-MHC mRNA levels had increased by 11-fold and alpha-MHC mRNA levels had decreased by about 30%. These changes corresponded to an increase in the relative proportion of beta MHC protein, from undetectable levels at 2 months, to about 40% by 8 months and to about 60% by 23 months. Increased levels of beta-MHC and its mRNA in older rats correlated with decreased serum thyroid hormone levels. The specific activity of creatine kinase in crude homogenates decreased with age, as has been reported previously. Relative to 2-month controls, the specific activity of creatine kinase had decreased by 21% at 8 months and by 37% at 23 months. Analysis of creatine kinase activity showed no large increase in levels of the fetal (B) isoform with age, as was found for myosin. Levels of mRNAs encoding the B and M isoforms of creatine kinase were significantly reduced in senescent rats. Thus, the decreased levels of creatine kinase in aging rats is correlated with decreased levels of mRNA encoding the BCK and MCK isoforms but not an isoform shift. PMID- 2259253 TI - Comparison of myosin and creatine kinase isoforms in left ventricles of young and senescent Fischer 344 rats after treatment with triiodothyronine. AB - The effects of perturbation of thyroid hormone levels on expression of myosin and creatine kinase isoforms were examined in maturing and senescent rats. Whereas LV of maturing rats contain only alpha-MHC, LV of senescent rats contain nearly equal amounts of both alpha-MHC and beta-MHC. When maturing rats were made hypothyroid by treatment for 14 days with the antithyroid agent, propylthiouracil (PTU), beta-MHC and beta-MHC mRNA levels increased significantly. Administration of T3 to senescent rats, or maturing rats made hypothyroid by PTU treatment produced similar decreases in levels of both beta-MHC and beta-MHC mRNA. In contrast, treatment with T3 produced little change in creatine kinase isoform distribution. Thus, thyroid hormone appears to play a critical role in regulating expression of the isoforms of myosin but not of creatine kinase. PMID- 2259254 TI - Modulation of ovariectomy-related bone loss by parathyroid hormone in rats. AB - Studies were carried out to examine whether parathyroid hormone (PTH) will prevent the age-related bone loss that results from ovarian hormone deficiency and to explore the mechanism of its action. Ovariectomy caused a significant decrease in bone density in the distal metaphysis and mid-diaphysis, but not in the vertebra and proximal metaphysis. The decrease was prevented by PTH injection and in all the bones examined PTH administration increased bone density and bone calcium content above the levels in sham-operated controls. Similar findings were made in bone hydroxyproline levels. PTH treated ovariectomized animals had lower serum 25(OH)vitamin D and higher 1,25(OH)2 vitamin D levels than ovariectomized and sham operated animals that received solvent vehicle. Compared to the sham operated controls, ovariectomy caused a 4.5-fold increase in the number of tartrate resistant acid phosphatase (TRAP) positive multinuclear cells. This increase did not occur in PTH-treated animals. We conclude that PTH is effective in preventing ovarian hormone deficiency bone loss in rats. PTH may mediate this effect partly by stimulating osteoblastic bone formation and partly by increasing 1,25(OH)2 vitamin D-mediated calcium absorption. The data from TRAP positive multinuclear cells indicate that an etiologic component of ovarian hormone deficiency bone loss is the expansion of a pool of osteoclast progenitors and that the bone anabolic action of PTH involves, in part, a decrease in bone resorption as a result of the suppression of the proliferation of osteoclast progenitors. PMID- 2259255 TI - Nuclear proteins and chromatin structure in liver and intestinal epithelial cells of young growing and adult rats. AB - Nuclei from liver and intestinal epithelial cells of young growing rats (39 days old) and adult rats (98 days old) were isolated. After addition of DNase I, the chromatin was separated by centrifugation (1100 g) into two fractions; the pellet (P) and the supernatant (S). The amount of chromatin released into the S-fraction was the same for the two age groups. The intestinal epithelial cell nuclei underwent self-digestion (in the absence of added DNase I) which was significantly higher in the young rats than in the adults. Subsequent examination using immunotechniques established the presence of non-sarcomeric myosin heavy chain indicating that active genes were present for that protein. Hybridization of DNA with cDNA specific for myosin heavy-chain revealed that, relative to total DNA, the DNA retained in the P-fraction of both tissues and age groups contained the same amount of hybridizable sequences. In liver, nuclear proteins decreased significantly with age per g wet weight of tissue. In the enterocyte tissue, total DNA and protein increased with age. SDS-polyacrylamide gel or acetic acid urea gel electrophoresis gave no age-related differences in the pattern of the proteins within each tissue. The results show that both liver nuclear DNA and protein decrease with age per g wet weight but increase per total tissue. In intestinal epithelial cells changes in chromatin structure with age were inherent within the nucleus. PMID- 2259257 TI - Age-related decrease in the number of hemopoietic stem cells and progenitors in senescence accelerated mice. AB - Senescence accelerated mice (SAM-P) were used for the study of the possible aging of hemopoiesis. The number of peripheral leukocytes decreased significantly with age, whereas hematocrit showed only a slight decrease. Although the number of total nucleated cells in the bone marrow increased, the number of hemopoietic stem cells (CFU-S) as well as that of granulocyte-macrophage colony forming cells (GM-CFC) showed a decrease in old mice. A significant decrease in the number of GM-CFC was observed in the spleen of old SAM-P mice, whereas no decrease was found in the number of CFU-S. Such a profound reduction of the recruitment of GM CFC from CFU-S in the spleen together with a reduction of bone marrow hemopoiesis may be responsible for the decrease in the number of peripheral leukocytes in the old mice. SAM-P mice could provide a good model for the study of the aging of hemopoietic system. PMID- 2259256 TI - Gonadal function in aging rats and its relation to pituitary and mammary pathology. AB - In the female rat, aging is characterized by a high incidence of prolactin (Prl) secreting pituitary adenomas and mammary tumors. In contrast to this, old males show only a moderate to low incidence of pituitary and mammary pathology. Since gonadal steroids and Prl are thought to be key factors in the genesis of the above neoplastic pathologies, it was of interest to compare the serum levels of progesterone (P), estradiol (E2), testosterone (T) and Prl with the incidence of pituitary and mammary tumors in aging male and female rats. Young (3-4-month; YF), old (25-month; OF) and senescent (33-35-month; SF) female and young (3-4 month; YM) and old (24-26-month; OM) male Sprague-Dawley rats were killed by decapitation and their pituitaries weighed. Serum sex steroids and Prl were measured by RIA. The average life span of females but not males was markedly extended by systematic removal of mammary tumors. Females showed a rising incidence of mammary tumors after 14 months of age. In males, this pathology which began to appear at 16 months, had a much lower incidence than in females at all ages. Serum levels of E2 were (means +/- S.E.M.) 22.0 +/- 1.6; 18.9 +/- 0.8; 32.9 +/- 2.5; 37.3 +/- 2.0 and 32.2 +/- 3.0 pg/ml for YM, OM, YF, OF and SF, respectively. Serum P was 1.4 +/- 0.3; 1.6 +/- 0.2; 10.4 +/- 2.2; 9.7 +/- 3.3 and 6.8 +/- 0.8 ng/ml for YM, OM, YF, OF and SF, respectively. Serum T was 1578.9 +/- 188.7; 807.6 +/- 103.0; 197.5 +/- 11.8; 223.7 +/- 25.5 and 176.9 +/- 20.7 pg/ml for YM, OM, YF, OF and SF, respectively. Finally, serum Prl was 14.9 +/- 1.7; 21.9 +/- 4.0; 15.9 +/- 1.4; 52.4 +/- 9.4 and 170.8 +/- 31.1 ng/ml for YM, OM, YF, OF and SF, respectively. A strong correlation was found between serum Prl and anterior pituitary weight in OM, OF and SF, but not between serum Prl and sex steroid levels or sex steroid ratios. We conclude that, although the sex-related differences in mammary and pituitary tumor incidence during aging in rats can be partially accounted for by the different serum profiles of Prl and gonadal steroids in each sex, sex-associated differences in target tissue susceptibility should also be considered as an important determinant of the level of tumor incidence. PMID- 2259258 TI - [Pancreatic islet cell transplantation]. PMID- 2259259 TI - [In vitro and in vivo studies of isolation, transplantation and function of Langerhans islets in the swine]. AB - Limits and possibilities of the transplantation of islets of Langerhans in pigs were studied. 6 x 10(4) to 3 x 10(6) islets and insulin producing fragments per pancreas were obtained by intraductal collagenase digestion of the pancreatic gland following total pancreatectomy. Islets grafted into the spleen or liver rendered normoglycemia to the pancreatectomized animals as demonstrated by normal fasting blood sugars and normal intravenous glucose tolerance tests as compared to not operated animals permitting a survival time of up to one year. Apancreatic controls died of ketoacidosis and diabetic coma 10 to 12 days posttransplant. The number of isolated and transplanted islets correlated well to the normoglycemic state of the animal. Beyond that the in vitro challenge of the islets with glucose and resulting insulin secretion was a very important indicator for the functional status and integrity of the islets after transplantation. Thus the pig appears to be a suitable model for the preclinical studying of islet transplantation especially since immunologic, physiologic and anatomic features of the pig are similar to those in the human regarding pancreas and nutrition. PMID- 2259260 TI - [Prognostically relevant factors in follicular thyroid cancer]. AB - The discussion of the prognosis of follicular thyroid carcinoma is controversial. To evaluate the factors which influence the prognosis we retrospectively analyzed our patients from 1. 1. 1964 to 31. 12. 1987. 76 patients with a follicular thyroid carcinoma were treated during this time. Factors influencing the prognosis were: (1) multiple tumor growth; (2) pT-classification; (3) vascular invasion; (4) tumor stage; (5) degree of cellular differentiation and (6) metastases. Because of the prognostic influence of multiple tumor growth and the slight prognostic influence of lymph node metastases we recommend a total thyroidectomy with neck dissection for follicular thyroid carcinoma. PMID- 2259261 TI - [Value of preoperative diagnosis in mesenteric vascular occlusion. A prospective study]. AB - In a prospective study the value of preoperative diagnostics in acute mesenteric vascular occlusion was investigated in 46 patients. Seventeen patients had an arterial thrombosis, 17 a venous thrombosis, 10 had an emboli and 2 patients suffered from a non-occlusive mesenteric infarction. All patients had leucocytosis with an average of 21,000/nl; serum lactate was increased in 91.4% and phosphate was increased in 36.4%. In 82.6% of the cases loops of the small bowel were seen on the X-ray of the abdomen, but in none of the patients an acute mesenteric vascular occlusion was suspected based on the X-ray alone. In 5 of the 46 cases the occlusion could be seen sonographically. The angiography had a sensitivity of 77%. PMID- 2259262 TI - [Colon necrosis as a complication of necrotizing pancreatitis]. AB - Necrosis of the colon is a rare but often fatal complication of necrotizing pancreatitis. Among 159 patients with necrotizing pancreatitis who were treated between 1 January 1986 and 31 December 1988, a colonic lesion developed in 10 patients (6.3%). All 10 patients underwent surgery. With regard to the time of occurrence and the extent of the lesion two types could be distinguished: first, extensive, probably ischemic colonic necrosis developed early in the course of the disease, i.e., within the 1st week; second, localized lesions mainly in the region of the left colonic flexure occurred much later and were considered to be a complication related to persistent infection in the remaining pancreatic necroses. The colonic lesions were treated by resection and fecal diversion in 9 patients and by local excision with direct closure and additional diverting colostomy in one patient. Even though the colonic complications could be controlled, only 1 of the 10 patients survived. This can be explained by the fact that all these patients had a severe form of the disease with extensive pancreatic necroses and were in a septic-toxic state with multiple organ failure at the time the colonic lesion occurred. PMID- 2259263 TI - [The course of fibers in the central tendon]. AB - In each polytrauma a diaphragmatic rupture is possible. Usually the rupture is located in the central tendon. A cause of the bizarre form of ruptures is the individual arrangement of gaps between the fibres of the central tendon. These fibres are classified in three groups. A rupture is generally on the left side of the central tendon. A further cause of the relative rare rupture on the right side is beside protection by the liver the greater stability on the right side of the central tendon, because fibres are more interlocked. The diaphragmatic rupture of a polytrauma is often overlooked, this number could be reduced by specific diagnostics. The repair of a diaphragmatic rupture is not a problem, an abdominal approach should be preferred. The prognosis depends on extension of concomitant lesions. PMID- 2259264 TI - [Hemosuccus pancreaticus]. AB - We describe a case of hemorrhage into the pancreatic duct, secondary to a bleeding aneurysm of the splenic artery. The problem of the diagnosis of this rare cause of upper gastrointestinal hemorrhage and therapeutic possibilities with their recurrency and mortality rates under short review of literature are discussed. PMID- 2259265 TI - [An anatomic study of the pancreatic lymphatics. Review of the summary and an abridged version of the original text]. AB - A detailed study of the lymphatics around the pancreas was carried out in order to provide a theoretic basis for ideal lymph-node resection in radical cancer operations. The following results were obtained as a result of minute macroscopic dissection of the lymphatics. Three major pathways are identified on the anterior surface of the head of the pancreas. The upper pathway belongs to the common hepatic group. The middle and lower routes are associated with the superior mesenteric nodal group. All these pathways terminate in the node situated to the right of the origins of the celiac trunk and the superior mesenteric artery. The lymphatics arising from the neck of the pancreas also converge at the same node. Behind this node, there is a terminal node for the lymphatics which arise from the posterior surface of the head. Both nodes are firmly adherent, with only the nerve plexus of the head of the pancreas intervening. In this study, we have named these lymph-nodes Lnn celiacomesenterici dextri superficialis et profundi. Two distinct pathways are identified in the left half of the pancreas. One follows the splenic blood vessels and the other accompanies the inferior pancreatic artery. By way of these routes, lymphatics from the left half of the pancreas terminate in the node situated to the left of the origins of the celiac trunk and superior mesenteric artery. We have applied the term Ln celiacomesentericus sinister to this node.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259266 TI - [Vasculature based segmental resection of the liver]. AB - Complete surgical resection represents the only treatment for malignant tumors of the liver which offers the chance of long-term tumor-free survival. From this oncological perspective the segment orientated approach appears to be a valuable supplement of traditional hepatic surgery. It minimizes incomplete tumour removal, and prevents a waste of non-involved hepatic tissue. This combination of optimum local radicality and maximum parenchyma preservation also reduces operative risk. Various modern diagnostic and surgical aids such as intraoperative ultrasound, liver transection using the ultrasonic aspirator, and control of bleeding by means of infrared coagulation or fibrin tissue adhesive, all do considerably support this individualized surgical approach. However, the practical application is essentially based on the intrahepatic vasculature and the thereby defined segmental anatomy. The sequence of the operative proceeding will be illustrated for different mono- and polysegmentectomies. PMID- 2259267 TI - [Partial lobe resection, or hemithyroidectomy in surgery of the isolated thyroid nodule?]. PMID- 2259268 TI - A presumptive role for GABA in the stimulatory effects of Des-Gly10, [D-Ala6] LHRH-ethylamide and pimozide on the gonadotropin release in carp. AB - To investigate the effect of endogenous gamma-aminobutyric acid (GABA) on the blood maturating gonadotropin (GtH) levels, or to study its interaction with pimozide (dopamine antagonist) and a luteinizing hormone-releasing hormone analog (LHRH-a), sexually mature male and female carps were treated with drugs that may either inhibit GABA biosynthesis or GABA degradation. In females the irreversible inhibitor of GABA-transaminase, gamma-vinyl GABA (GVG), which was to increase the endogenous GABA-ergic tone, had no influence on GtH release. On the other hand, the increased GtH response to the combination of pimozide (PIM) and LHRH-a was clearly enhanced by the administration of 3-mercaptopropionic acid (MPA), an inhibitor of the rate limiting enzyme of GABA-biosynthesis. In males the GABA ergic compound, valproic acid (DPA) decreased LHRH-a stimulated GtH levels. In male carps that received PIM to diminish the dopaminergic inhibition of GtH release, the spermiating response to LHRH-a was increased by administration of MPA. These data suggest that GABA interacts with the action of dopamine and the gonadotropin releasing hormone (GnRH) on the release of GtH. PMID- 2259269 TI - Increased pulmonary metastases and natural killer cell activity in mice following handling. AB - We have demonstrated that holding BALB/c female mice for two minutes per day for two weeks prior to injection of line 1, a BALB/c derived alveolar carcinoma, results in a significant increase in pulmonary metastases compared to unhandled controls. Handling did not affect splenic in vitro or in vivo natural killer (NK) cell activity but, surprisingly, was associated with increased NK cell activity in the lungs of these handled mice. These results demonstrate that a simple psychosocial manipulation may effect the metastatic process. The implications of these findings and potential mechanisms are discussed. PMID- 2259270 TI - Intracellular accumulation of isoproterenol enhances the lactate production in the perfused rat heart. AB - Effects of intracellular accumulation of isoproterenol (ISO) on lactate production were examined in perfused rat heart. The lactate production during ISO perfusion in rat heart was increased and subsequent addition of an inhibitor of catechol-O-methyl transferase (COMT) further enhanced the production, and the enhanced production was significantly reduced by uptake2 inhibitor. The perfusion with ISO free-medium in the heart with high intracellular accumulation of ISO produced lactate more than that in the low intracellular accumulation. The present experiments demonstrated that the enhanced lactate production is accompanied by intracellular accumulation of ISO in the perfused rat heart, and suggested that the accumulated ISO may activate intracellular beta-adrenoceptors in the rat heart. PMID- 2259271 TI - Plasma concentrations of endothelin in patients with abnormal vascular reactivity. Effects of ergometric exercise and acute saline loading. AB - We measured circulating concentrations of endothelin, a recently discovered vasoconstrictor peptide produced by vascular endothelial cells, in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radio-immunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects (n = 20), in patients with diabetes mellitus type I (n = 10), in patients with mild to moderate essential hypertension (n = 12) and in non-dialyzed patients with stable chronic renal failure (n = 12). Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0 +/- 0.6 pg/ml, 4.7 +/- 0.2 pg/ml and 6.5 +/- 1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6 +/- 2.9 pg/ml (p less than 0.005). No correlations were observed between serum creatinine concentrations ranging from 124 to 850 mumol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin. Thus, it is unlikely that vascular synthesis of endothelin is related to acute physiological changes in systemic hemodynamics or to the circulatory and renal responses to acute extracellular fluid volume (ECFV) expansion. A potential role of endothelin, however, in the control of regional blood flow cannot be excluded. Elevated plasma concentrations of endothelin observed in patients with chronic renal failure require further investigations. PMID- 2259272 TI - [A simplified method for the radionuclide determination of glomerular filtration]. AB - Glomerular filtration is one of the chief components of renal function. The biochemical methods of its determination (clearance of insulin and endogenous creatinine) have a number of shortcomings. The use of labeled glomerulotropic agents simplifies methods of the determination of glomerular filtration. A formula and a table of glomerular filtration value per 1 kg of body mass were calculated. The authors presented the results of glomerular filtration calculation for 132 patients. They showed good correlation. The correlation factor is r = + 0.916 (mr = 0.009). PMID- 2259273 TI - [The determination of the activity of natural killer cells in chronic lympholeukemia based on radiometric and morphological data]. AB - Function of lymphocytes as effector cells of natural cytotoxicity in chronic lympholeukemia was investigated using radiometric and morphological methods. The effectiveness of these methods was compared. A significant decrease in NKC activity in B-cell type of chronic lympholeukemia was detected. A high degree of positive correlation between radiometry and morphology findings was revealed. The radionuclide (51Cr) method of investigation of NKC activity of lymphocytes was shown to have more advantages over the alternative morphological method in terms of practicability, accuracy and objectiveness. PMID- 2259274 TI - [The ultrasonic detection of the metastatic involvement of the intra-abdominal and retroperitoneal lymph nodes in esophageal cancer]. AB - The paper is based on analysis of the results of ultrasound investigation of 67 patients with esophageal cancer with metastatic involvement of abdominal and retroperitoneal lymph nodes verified at operation. For effective diagnosis of these changes during ultrasound scanning one should observe the main methodological principles and methods including polyprojection, polyposition and staging of investigation. It should be noted that unchanged lymph nodes cannot be visualized. PMID- 2259275 TI - [The possibilities of x-ray study in assessing the results of the radiation treatment of laryngeal cancer]. AB - The paper is devoted to comparing laryngoscopy findings and the results of x-ray investigation in its time course (prior to, during and after radiation therapy) in 65 laryngeal cancer patients. Both methods are mutually complementary, and thorough comparison of their results helped to overcome diagnostic difficulties. The basal point and spreading of exophytic supralaryngeal tumors can be determined by x-ray only. The greatest diagnostic difficulties occur after therapy to differentiate between postradiation mucosal edema and a tumor relapse. PMID- 2259276 TI - [Synergism in the action of gamma radiation and cardiac glycosides]. AB - Synergism of gamma radiation with 137Cs and cardiac glycosides was investigated in experiments on mice and transplantable Raji tumor cells. A single ip administration of these drugs at nontoxic concentrations 30-60 min. after irradiation at the LD30/30 resulted in the survival of 13-20% of animals and the reduction of the mean survival time up to 8.4-12.5 days versus 22.3 days in the control group. Synergism was slightly decreased at administration of glycosides 24 h after irradiation. Glycosides introduced in the irradiated (at a dose of 1 2.5 Gy) human lymphoblastic line caused sharp suppression of lymphoma growth and cellular lysis in experiments in vitro. One hundred per cent death of cells was noted after the use of the drugs at mean toxic concentrations. PMID- 2259277 TI - [The behavior of 125I microspheres of serum albumin in the body of rabbits administered the preparation selectively into the renal artery]. AB - Intraarterial selective injection of serum albumin microspheres into the kidney resulted in embolization of the vessels with microspheres of different sizes. In vivo radiometry made it possible to improve the localization of microspheres and their distribution in the animals' bodies at varying time of observation. Pathomorphological investigations showed optimum sizes of microspheres causing prolonged retention of microparticles at the site of injection without considerable morphological changes of body tissues. The method of using microspheres as a radionuclide carrier was shown to hold promise for therapeutic purposes. PMID- 2259278 TI - [The optimization of the dosimetric plan in the intracavity radiotherapy of patients with cancer of the corpus uteri]. AB - The potentialities of mathematical optimization were investigated with respect to dosimetric design of radiation therapy of endometrial cancer patients using AGAT V and AGAT-VU [correction of Agat-B and Agat-Y] apparatus. The effectiveness of linear programming for creating in a pathological focus and in normal tissues of a dose distribution, meeting clinical requirements to the maximum, was shown. PMID- 2259279 TI - [Dynamic esophageal scintigraphy by a condensed imaging method]. AB - The paper is concerned with preliminary evaluation of a method of condensed imaging during processing of the results of dynamic esophageal scintigraphy to detect motor evacuatory function of the esophagus. Altogether 34 patients (20 patients with primary esophageal cancer and 14 without G. I. tract pathology) were investigated. Comparison of the results of analysis of dynamic esophageal scintigraphy by a method of condensed imaging and standard methods of diagnostic data processing has shown that a condensed image of the esophagus objectively reflects some passage features of a food lump in the organ. Condensed imaging seems superior for analysis of the results of investigation and diagnostic data storage. However, this method must not be regarded as an alternative one ruling out a necessity of analysis of esophageal histograms and calculation of RP transport in the esophagus. PMID- 2259280 TI - [A method for assessing the radiation loads on personnel and patients in accident situations with gamma therapy apparatus]. AB - The authors proposed drawing up maps of dose rate distribution under the conditions simulating patient's irradiation for each gamma therapeutic unit in order to estimate a degree of danger of excess irradiation of medical staff and patients during patient's evacuation resulting from a defective unit (incomplete closure of locks in distant irradiation and sources getting stuck in endostats in interstitial therapy). The timing of measures for evacuation of a patient from an emergency room made it possible to calculate accurately equivalent doses to which a radiologist, a technician and a patient were exposed. PMID- 2259281 TI - [The importance of a test control for the quality of a radiopharmaceutical preparation and its reagents used in neurosurgery]. PMID- 2259282 TI - [The interstitial radiotherapy of lung cancer using enclosed 125I radiation sources]. PMID- 2259283 TI - [An analysis of 3-dimensional images in radiodiagnosis]. PMID- 2259284 TI - [Radionuclide-labelled liposomes for demonstrating malignant neoplasms]. PMID- 2259285 TI - [Dynamic renal scintigraphy in assessing kidney function in patients with nonspecific colitis]. AB - Research into the morphofunctional status of the kidneys was conducted in patients with nonspecific colitis-NC (nonspecific ulcerative colitis-NUC and Crohn's disease). Urodynamics and partial function of the kidneys were assessed in 74 NC patients (51 NUC patients and 23 patients with Crohn's disease) on the basis of the findings of two-nuclide dynamic renal scintigraphy with 131I hippuran and 99mTc-pentatech. Despite the absence of clinical symptomatology of urinary tract lesions, marked dysfunction of the kidneys of various degree (depending on severity of disease, tactics of its treatment and a type of surgical intervention) was noted in NC patients. In most cases changes of renal function were without visible clinical manifestations and were frequently undetectable by routine laboratory tests. Therefore dynamic renal scintigraphy was found necessary for investigation on NC patients. PMID- 2259286 TI - Relative effectiveness of yeast cell wall digesting enzymes on Yarrowia lipolytica. AB - Novozym 234 at a concentration of 1.0 mg/ml yielded 95.5% spheroplasts within 30 min at 37 degrees C, pH 7.0, with 36% regeneration which was the highest level of regeneration observed. Yeast lytic enzyme at a concentration of 1.0 mg/ml yielded 99.8% spheroplasts with only 1.5% regeneration. Glusulase was significantly less active in producing osmotically sensitive cells. All three enzymes yielded significantly higher levels of osmotically sensitive cells when cells were harvested from the mid-logarithmic phase of growth compared with later growth phases. beta-Glucuronidase failed to produce osmotically sensitive cells regardless of the phase of growth from which cells were harvested. PMID- 2259287 TI - Thiamine requirement of Eikenella corrodens. AB - The thiamine requirement for growth of Eikenella corrodens was investigated. Autoclaved thiamine at a concentration of 1.0 microgram/ml supported maximal growth whereas for the same growth, filter-sterilized thiamine was required at 50 100 micrograms/ml. Studies with two thiamine degradation products, 2-methyl-4 amino-5-hydroxymethylpyrimidine and 4-methyl-5-(B-hydroxyethyl) thiazole, indicated that selected strains grew poorly or not at all in the presence of either moiety alone. However, the two moieties at a combined concentration of 0.02 microgram/ml supported growth equivalent to that of 1.0 microgram/ml of autoclaved thiamine. The requirement for a high concentration of filter sterilized thiamine may reflect a faulty thiamine uptake apparatus and the observed growth response may be due to the presence of the moieties in the commercial thiamine preparation. PMID- 2259288 TI - Bacterial production of histamine in some tropical fish. AB - Quantitative and qualitative distribution of histamine-forming bacteria associated with the fish Rastrelliger kanagurta, Sardinella longiceps, Sillago sihama and Liza subviridis, were investigated. These bacteria constituted a significant portion of the total bacterial population of fish and the values obtained in the present study were higher than those previously reported. The order of quantitative abundance of histamine-forming bacteria in the fish examined was: S. longiceps greater than R. kanagurta greater than S. sihama greater than L. subviridis. The bacterial genera isolated were Vibrio sp., Bacillus sp., Pseudomonas sp., Aeromonas sp. and Micrococcus sp., and among them Vibrio was dominant. Growth of the isolates (Vibrio sp., V. fischeri and Bacillus sp.) at different temperatures, pH and sodium chloride concentrations indicated them to be mesophilic, euryhaline and tolerant to acidic and alkaline pH. Bacillus sp. produced more histamine in R. kanagurta, while V. fisheri produced more histamine in S. longiceps. PMID- 2259289 TI - Mineralization of S from dibenzothiophene, dibenzothiophene sulphone, and benzene sulphonic acid by soil isolates. AB - The presence of substantial levels of organic S in coal is a major source of air pollution, and considerable efforts are being made to devise a cost-effective way of removing this form of sulphur. One method is to develop naturally occurring bacteria capable of heterocyclic organic S degradation and S mineralization. In this study, fourteen isolates capable of dibenzothiophene (DBT), dibenzothiophene sulphone (DBTS) or benzene sulphonic acid (BSA) decomposition were obtained from samples collected from an abandoned strip mine. The degradation of DBT varied from 4.4 to 91% and the mineralization of S as sulphate was less than or equal to 1.5%. Higher rates of DBTS decomposition were determined (94.9 to 97.7%) and S mineralization varied from 21.8 to 30.8%. The extent of BSA degradation could not be determined, but 57.8 to 71.1% of the S was mineralized as sulphate. All of the soil isolates possessed a single plasmid 20 to 23 kb in size. PMID- 2259290 TI - Uptake of manganese by Penicillium notatum. AB - Intact mycelium and protoplasts of Penicillium notatum were shown to take up manganese ions by an energy-dependent, high affinity uptake mechanism. Uptake was not inhibited by a range of divalent metal ions including Mg2+, indicating that manganese uptake by this process was specific. PMID- 2259291 TI - Accessibility and possibility of elimination of breast epithelium: the theoretical possibility of preventing breast carcinoma through destruction of the epithelium of origin. AB - Two characteristics of breast biology appear to constitute weak points in the fight against breast carcinoma. First, the epithelium from which breast carcinoma arises is of relatively easy accessibility, as it lines cavities which are in close communication with the outside. Second, the elimination of breast epithelium can be tolerated by the organism. Theoretically, breast carcinoma may be prevented by destroying breast epithelium through the injection of an agent into the ductal orifices at the nipple. This strategy appears relatively easy to perform in comparison with conventional strategies, which have not given reliable results. Therefore the possibility presented here should not be neglected. PMID- 2259292 TI - Higher molecular weight insulin precursors as autoantigens in type I diabetes. AB - Hypothetically, the formation of abnormal insulin precursors due to genetic and/or acquired disorders would result in autoantigens by virtue of the altered tertiary structure. These are unlikely to be accessible to the converting enzymes which in turn should produce extended exposure to the immune system. Subsequent humoral and cell-mediated immune response might thus initiate or aggravate the autoimmune destruction of B-cells in subjects genetically susceptible to Type I diabetes. PMID- 2259293 TI - Myocardial reperfusion injury: an assessment by the spasm of resistance vessel concept of ischemic heart disease. AB - Myocardial reperfusion injury will be discussed in context to the spasm of resistance vessel concept of ischemic heart disease. This hypothesis attributes symptoms in this disorder directly to primary spasm of resistance vessels, and is based in part on a study of no-reflow which provided evidence that no-reflow is due to ischemia-induced injury-spasm of resistance vessels. Studies of no-reflow and reperfusion injury are rather similar, and the concept asserts that ischemia induced injury-spasm causing no-reflow is involved in reperfusion injury. It is recognized that oxygen free radicals cause both myocardial and vascular injury during reperfusion injury, and the concept suggests that vascular injury contributes significantly to reperfusion injury by inducing the sequence of injury-spasm, no-reflow, fresh ischemia, and fresh ischemic reperfusion injury. In keeping with this, the possible involvement of spasm and no-reflow in reperfusion injury occasionally is mentioned. However, it seems to be generally accepted that reperfusion injury is due essentially solely to direct myocardial injury by free radicals, and possible reasons will be explored for a relative disinterest in spasm and no-reflow in reperfusion injury. PMID- 2259294 TI - Functional and therapeutic aspects of counter current transfer in the female adnexa. AB - Counter current transfer of many substances, including steroids and peptide hormones, takes place from the veins and lymph vessels to the arterial blood in the female adnexa. The vascular system to the ovaries, tubes, uterus, and vagina is involved, and transfer from one organ to another is possible due to the anatomy and physiology of the vessels. Examples of physiological importance are given: regulation of luteolysis, unilateral effects on the functions of the ovary and tube. The transfer may be used as a therapeutic tool in order to obtain high local concentrations of drugs. It is postulated that a hormone releasing intra uterine device (IUD) may have a local effect on the tubes and ovaries. It is also postulated that intrauterine instillation of cytotoxic drugs may be used before surgery in order to obtain a high concentration in local arterial blood when compared to the concentration in peripheral blood, thus obtaining a favourable therapeutic index between local beneficial and general toxic effects. The treatment may also create a high concentration of the drug in the local lymph glands and thus have a direct therapeutic effect on eventual metastasis. PMID- 2259295 TI - Phenomenological kinetics of pharmacological response. AB - The evaluation and quantitative analysis of the time course of drug response are difficult tasks even in uncomplicated fields of pharmacology. In an attempt to assist the analysis of the pharmacological effect, a procedure is presented which incorporates widely used intuitive-experimental practices of evaluation, and descriptive kinetic functions. The aim is to find a simple function which can approximate the time course of the response curves at different doses. Having estimated the values of parameters for each curve, valuable information can be drawn by examining the dose-parameter relationships. The method is illustrated by one possible evaluation and interpretation of the blood pressure-time curves of a drug. PMID- 2259296 TI - Why the incidence of cancer is increasing: the role of 'light pollution'. AB - At present, cancer is responsible for almost half of all deaths among women 45-64 years of age, and about 30% of all deaths among men in the same age group (1). This high rate represents a marked increase from the end of the last century (2), and it probably has a multifactorial etiology. Air pollution, smoking, diet, alcohol, occupational exposures and stress are all considered as possible etiologic and risk factors (3). We put forward a hypothesis that one of the most important etiologic factors in the rapid growth rate of cancer is the change of light exposure that took place in the last 100 years, especially in the developed countries. Increased light exposure acting through the pineal gland reduces melatonin production, thereby diminishing the non-specific oncostatic effects of the pineal gland. PMID- 2259297 TI - Relative stimulatory efficiency of various points on the surface of hemopoietic source cells. AB - We make quantitative estimates for the relative stimulatory efficiency at various points on the membrane of a hemopoietic source. This cell produces a stimulus, P, which supports renewal of parasitic stem cells (SCs) in physical contact with the source's surface. We find that the tips of long pseudopods extending from the source's main body should have the highest stimulatory efficiency. PMID- 2259298 TI - Is Gompertzian or exponential kinetics a valid description of individual human cancer growth? AB - It is generally accepted that human cancers grow in an exponential or Gompertzian manner. This assumption is based on analysis of the growth of transplantable animal tumors and on averages of tumor growth in human populations. A computer model of breast cancer in individual patients has raised some doubts about this assumption. The computer model predicts an irregular pattern of tumor growth that incorporates plateaus or dormant periods separated by Gompertzian growth spurts. Since growth patterns involving plateaus are not predicted by conventionally accepted exponential or Gompertzian kinetics, sufficient documentation of their existence may be regarded as some evidence that the computer model is correct. The literature has been surveyed to identify growth patterns specifically predicted by the model. The literature contains clinical evidence from individual patients of this growth pattern in primary breast, large intestine and rectum, and pulmonary cancers and metastatic pulmonary cancer. Much data, including the only breast data, are not consistent with exponential or Gompertzian kinetics but are explainable by irregular growth kinetics. Exponential growth is valid for some tumors and for short times, but there are many papers citing significant deviations from that growth. Exponential growth may accurately describe averages of human tumor growth and growth of multipassaged experimental tumors, but it is not valid for all individual tumors. PMID- 2259299 TI - Sustaining life through art and medicine. PMID- 2259300 TI - The unity of medicine and literature. PMID- 2259301 TI - Literary medicine. PMID- 2259302 TI - To lend a hand. The magic of music and medicine. PMID- 2259303 TI - Rembrandt's 'Dr. Tulp's Anatomy Lesson'. PMID- 2259304 TI - Home heparin infusion in the management of deep vein thrombophlebitis. AB - Feasibility of home Heparin infusion in the management of deep vein thrombophlebitis (DVT) was assessed in 15 patients. Patients with chest pain, dyspnea, bleeding tendencies, immediate postoperative state, and lack of reliable care giver were excluded. Five patients received the entire course of Heparin infusion at home and 10 were initially started on Heparin in the hospital. Regular assessment and monitoring of blood coagulation parameters were performed by a visiting home nurse clinician in consultation with the attending physician. Eleven physicians were involved in this management and made a total of six physician home visits. Results showed improvement in all but one patient, who had advanced malignancy and resistant thrombophlebitis and who eventually died. No complications occurred among the patients studied. Patient and family surveys indicated a high degree of satisfaction and preference for this modality of care. Analysis of cost indicated a 48% savings compared with similar treatment administered in a hospital setting. PMID- 2259305 TI - Informed consent. Enhancing physician-patient communication. 2. PMID- 2259306 TI - A management perspective on the physician buy-in process. PMID- 2259307 TI - An office of rural health. A focal point for rural health concerns. PMID- 2259308 TI - Chronic pain treatment. PMID- 2259309 TI - Smoking cessation intervention. PMID- 2259310 TI - A look at today's hospital board. Minnesota Medicine interviews Roger Foussard. Interview by Richard L. Reece. PMID- 2259312 TI - Headache. PMID- 2259311 TI - Headache. Public health problem. AB - Headache is, and apparently always has been, a frequent pain syndrome. It is reported in American and Western European societies in very high percentages of the population. Headache, and specifically severe headache, have also been reported as prevalent from a variety of societies worldwide, although prevalence rates have varied (they are very low, for example, in the People's Republic of China). Whether prevalence varies with different socioeconomic groups remains uncertain. Severe headache and specifically migraine is, for reasons still unknown, much more common in women, and, in most studies, is reported to decrease in prevalence in older age groups. Positive family histories are common, but the precise role of genetics is unknown. A major problem in the epidemiologic studies remains the difficulty of uniform definition of headache syndromes. PMID- 2259313 TI - The classification and diagnosis of headache disorders. AB - Headache disorders recently have been reclassified, and new operational diagnostic criteria assist in making the correct diagnosis. These diagnostic criteria have been accepted worldwide. PMID- 2259315 TI - Manifestations of migraine. AB - Migraine is a disorder with multiple manifestations affecting the circulation, gastrointestinal tract, and the central nervous system. Involvement of the autonomic nervous system is responsible for many of the clinical features. An attack of migraine can vary from a fragment of the clinical spectrum to one with several phases and potentially permanent sequelae. PMID- 2259314 TI - Developments in 5-hydroxytryptamine receptor pharmacology in migraine. AB - Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome. The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine. A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain. As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors. These receptors are present in certain intracranial blood vessels. 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters. Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain. Although these receptors are also found in certain blood vessels, they are present throughout the nervous system. The receptors appear to mediate neuronal depolarizations at the cellular level. Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems. Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine. These data offer a novel approach to the analysis of antimigraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine. Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome. PMID- 2259316 TI - Modern pharmacotherapy of migraine. AB - Rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks; for particularly dramatic episodes, intravenous DHE with prochlorperazine is the author's preference. For long-term stabilization, after simpler measures fail, valproate appears to be a major addition to migraine therapy. PMID- 2259317 TI - Advances in cluster headache. AB - The physician may have to combine the art and science of medicine in the management of this most fascinating of human ailments. The choice of drugs and the length of treatment prescribed are greatly influenced by the individual physician's experience, convictions, and reasoning. Needless to say, chronic use of narcotics should be avoided. The author's own regimen is to use combinations of ergotamine prophylaxis with either verapamil or prednisone in episodic cluster headache and with lithium for chronic cluster headache. Management of the treatment-resistant patient remains problematic, but a carefully performed trigeminal radiofrequency thermocoagulation procedure may be worthwhile. PMID- 2259318 TI - Drug-induced headache. AB - Headache induced by medications used for nonheadache conditions, and more importantly, headache perpetuated by symptomatic medications used for primary headache disorders are discussed in detail in this article. The clinical features and mechanisms of drug-induced headaches are reviewed. Ergotamine and analgesic rebound phenomena are described. Management strategies for drug-induced headaches are outlined. PMID- 2259319 TI - Facial pain. AB - This article presents differential diagnosis and treatment of facial pain. Facial pain is classified in accordance with the recent work of the Headache Classification Committee of the International Headache Society. The two major divisions are facial pain associated with disorders of the head and neck, including their parts, and disorders of cranial nerves, including their central connections. Special attention is paid to the controversial topics of temporomandibular joint dysfunction and atypical facial pain. PMID- 2259320 TI - Oromandibular disorders and headache. A critical appraisal. AB - Oromandibular disorders are functional disorders and associated pains in the anatomic region of the temporomandibular joint. Their diagnosis and treatment are controversial because of the lack of conformity concerning these disorders among health care providers. This article provides a clear classification of these disorders and critically reviews their evaluation and treatment. PMID- 2259321 TI - Headache and acquired immunodeficiency syndrome. AB - Because the acquired immunodeficiency syndrome (AIDS) virus is neurotropic, physicians will continue to see a rise in the number of neurologic complications of this syndrome. Much of this increase will be accompanied by headache, not only as a primary symptom of HIV infection or opportunistic disease but also as a result of diagnostic tests and therapeutic efforts. Complete understanding of the ramifications of headache in AIDS will be important in the 1990s as we continue to treat a younger population, usually affected by benign vascular and muscle contraction-type headache. PMID- 2259322 TI - Psychologic and behavioral aspects of chronic headache. AB - It is important for physicians to be aware of the expectations and psychologic needs patients have, to understand how psychologic and personality variables can impact care, to realize the importance of patient education, and to be cognizant of how environmental factors can influence headache pain behaviors. Empirical data indicate that the nonpharmacologic treatments of biofeedback, relaxation, and stress coping training can serve as useful adjunctive or alternative procedures, and that the combined use of medication and nonpharmacologic treatments yields the greatest clinical outcome. Certain headache types show minimal response to nondrug therapies alone (cluster, menstrual, and post traumatic headache). Age and personality variables have a bearing on nondrug treatment outcome as well. PMID- 2259323 TI - Oral contraceptives and breast cancer. PMID- 2259324 TI - Disappointment. PMID- 2259325 TI - Doctor, are your communication switches on? PMID- 2259326 TI - For your information: head injury. AB - Head injury causes more deaths and disabilities than any other neurologic cause in individuals under age 50. Skull fractures can tear the arteries and veins that supply the meninges (the protective membrane covering the brain), causing hemorrhage or intracranial pressure from the rapidly expanding mass of clotted blood. Meningitis-causing bacteria can be introduced via the small openings caused by skull fracture. Even closed head injuries (head injuries that do not result in displaced skull fractures) can cause bruising and tearing of brain tissue. In the medical management of patients with head injuries, family and friends can play a key role in post-treatment observation. PMID- 2259327 TI - Communication: chief of the seven "C"s of MSMA. PMID- 2259328 TI - Loxoscelism and the history of the Missouri brown spider: a recollection of Dr. Joseph Flynn. PMID- 2259329 TI - Breast cancer in Missouri: staging, survival, and mammography screening patterns. PMID- 2259330 TI - Oral contraceptives and breast cancer. AB - The possible relationship of oral contraception use to breast cancer is a concern to physicians and their patients. In this article, the authors present a review of the major studies conducted during the last 10 years, from an epidemiologic viewpoint. PMID- 2259331 TI - Agrobacterium tumefaciens T-DNA gene 6b stimulates rol-induced root formation, permits growth at high auxin concentrations and increases root size. AB - All Agrobacterium tumefaciens strains studied up to now transfer an active 6b gene to plant cells. However, the role of this gene in natural tumour induction is unknown. Various effects of 6b on plant cell growth have been described, but the precise mechanism by which 6b causes these effects has not been elucidated. Earlier experiments indicated that the 6b gene might increase auxin sensitivity as do the A. rhizogenes rol genes. The 6b gene from Tm4 (T-6b) was therefore compared with the rolB and rolABC genes. Although T-6b was unable to induce root formation, it strongly interfered with root induction and root elongation. In rolABC/T-6b coinfection experiments on carrots, T-6b-transformed cells stimulated root outgrowth of rolABC-transformed cells, indicating that the biologically active T-6b product is diffusible. Carrot rolABC roots containing the T-6b gene rapidly developed into unorganized calli. Nicotiana rustica roots with rolABC and T-6b continued their development, but became very large. Fragments of such roots formed callus at alpha-naphthaleneacetic acid concentrations which inhibited growth of rolABC and normal root fragments, suggesting that the role of 6b genes in natural tumour induction may be to reduce the inhibitory effects of high auxin levels and to keep cells in an undifferentiated state. PMID- 2259332 TI - Restoration of the yeast LEU2 gene by transcriptionally controlled recombination between tandem repeats. AB - The LEU2 gene of a his3 strain was inactivated by inserting the HIS3 gene between two overlapping inactive leu2 gene fragments, and mitotic stability of the resulting leu2:HIS3::leu2 sequence was measured under leucine repression and derepression. Both inactive leu2 regions were transcribed under derepressing conditions (growth in low leucine), and the LEU2 gene was completely restored by illegitimate recombination between the overlapping tandem repeats, leading to the loss of the intervening HIS3 gene. In contrast, only the downstream leu2 fragment was transcribed upon leucine repression, and the HIS3 insert in the leu2 region remained intact. The reciprocal experiment (inactivation of the HIS3 gene by inserting the marker gene LEU2) revealed a moderate rate of HIS3 restoration and LEU2 excision, reflecting transcriptional activity of the HIS3 region intermediate between that of LEU2 transcription in the repressed and derepressed state. PMID- 2259333 TI - Correct splicing of modified introns of a Rhizopus proteinase gene in Saccharomyces cerevisiae. AB - The intron of the Rhizopus aspartic proteinase gene (RNAP-I) was modified by in vitro mutagenesis and examined for its splicing efficiency in Saccharomyces cerevisiae. The wild-type intron of the RNAP-I gene was not spliced at all in spite of its structural similarity to introns of S. cerevisiae. The primary transcript of the RNAP-I gene was converted to correctly translatable mRNA only when the complete consensus sequence of S. cerevisiae introns (i.e. 5'-GTATGT---- TACTAAC-----TAG-3') was introduced into its intron, although the efficiency of splicing was low. It is also shown that transformants carrying the RNAP-I gene with the complete consensus sequence of S. cerevisiae introns produce active RNAP I protein. PMID- 2259334 TI - Transcription and regulation of expression of the Escherichia coli methionyl-tRNA synthetase gene. AB - The DNA sequence and transcriptional organization around the Escherichia coli methionyl-tRNA synthetase gene, metG, were resolved. This gene can be transcribed in vivo and in vitro from two distinct promoters separated by 510 nucleotides. The upstream promoter is located within the coding sequence of a divergent gene expressing a protein of Mr 39 kDa of unknown function. Transcription originating from this upstream promoter is attenuated by a Rho-independent terminator before entering the structural gene. This leader RNA contains several potentially stable secondary structures, one of which shows striking similarity to tRNA(Met), but no methionine-rich coding sequence. The regulation of metG expression was investigated by means of fusions to the lacZ gene. Transcription of a metG::lacZ fusion is induced in a metG mutant and, reciprocally, repression is observed in a methionyl-tRNA synthetase overproducing strain. A model of metG expression control is proposed. PMID- 2259335 TI - A translocation activating the cryptic nitrogen regulation gene areB inactivates a previously unidentified gene involved in glycerol utilisation in Aspergillus nidulans. AB - The chromosome VIII translocation breakpoint of the areB-404 translocation, selected for its ability to activate the cryptic nitrogen metabolism regulatory gene areB, and the mutation glcD-100 both lead to loss of mitochondrial FAD dependent sn-glycerol-3-phosphate dehydrogenase in Aspergillus nidulans. These two lesions therefore define glcD, a second gene (in addition to glcB) where mutation can result in loss of this enzyme. The glcD gene has been localised to a centromere-proximal region of the right arm of chromosome VIII. Although all six known areB-activating mutations involve chromosomal rearrangements and presumably therefore gene fusions, areB-404 is the first such rearrangement where the gene involved in an areB fusion has been identified. PMID- 2259337 TI - High efficiency transformation of Salmonella typhimurium and Salmonella typhi by electroporation. AB - Salmonella typhimurium and S. typhi were transformed with high efficiency by electroporation. Transformation efficiencies of up to 10(10) transformants per microgram of pBR322 were obtained. In contrast to chemical transformation methods, neither the smooth lipopolysaccharide of S. typhimurium nor the Vi capsular polysaccharide of S. typhi greatly affected transformation efficiency. The introduction of a ga1E mutation slightly improved transformation efficiency in S. typhimurium (less than tenfold) while the Vi antigen of S. typhi had no detectable effect. The transformation efficiency of S. typhimurium with DNA derived from Escherichia coli was increased greatly by the removal of the hsd restriction system (100-fold). Under these conditions electroporation can be used for the routine and direct transformation of Salmonella strains with partially purified (alkaline lysis) plasmid DNA from E. coli. PMID- 2259336 TI - A new gene (madI) involved in the phototropic response of Phycomyces. AB - Only eight genes are known to be involved in the phototropic response of Phycomyces (madA-H). Mutants affected in these genes have played a major role in the analysis of photosensory transduction processes in this system. A set of new mutants isolated by Alvarez et al. (1989) that are unable to bend towards dim unilateral blue light were studied by complementation and recombination. Two of these mutants have mutations in madE, one has a mutation in madF and one is a double madE madF mutant. The three remaining mutants tested did not complement each other and showed positive complementation with strains carrying mutations in the genes madA, madB, and madC, indicating that they carried mutations in a new gene designated madI. Recombination analysis showed that madI is unlinked to madA, madB and madC. PMID- 2259338 TI - Iron(III)hydroxamate transport of Escherichia coli K12: single amino acid replacements at potential ATP-binding sites inactivate the FhuC protein. AB - The mechanism of iron(III)hydroxamate transport appears to be of the periplasmic binding protein dependent transport (PBT) kind which is energized by ATP hydrolysis. The FhuC protein contains two domains typical of ATP-binding proteins. Lysine in domain I was replaced by glutamine and glutamate, and aspartate in domain II by asparagine and glutamate, resulting in FhuC derivatives which no longer transported ferrichrome and albomycin. FhuC inactivation by the aspartate-glutamate substitution is especially noteworthy since the negative charge thought to be involved in Mg2(+)-ATP binding remains the same and the two amino acid side chains differ in only a CH2 group. It is concluded that the two domains that represent consensus sequences among all peripheral cytoplasmic membrane proteins of PBT systems are involved in substrate transport. PMID- 2259340 TI - Presence in the stroma of chloroplasts of a large pool of a ribosomal protein not structurally related to any Escherichia coli ribosomal protein. PMID- 2259339 TI - Conserved repetition in the ice nucleation gene inaX from Xanthomonas campestris pv. translucens. AB - The nucleotide sequence was determined for the bacterial ice nucleation gene, inaX, from Xanthomonas campestris pathovar translucens X56S. Comparison of the nucleotide sequence of inaX to the previously characterized ice nucleation genes, inaZ from Pseudomonas syringae S203, inaW from Pseudomonas fluorescens MS1650, and iceE from Erwinia herbicola M1 revealed a 65.8%, 67.8%, and 68.8% homology, respectively. Within the internal, repetitive domain of the translated product of inaX are 153 consecutive octapeptide repeat units. PMID- 2259341 TI - Expression in Saccharomyces cerevisiae of a gene associated with cytoplasmic male sterility from maize: respiratory dysfunction and uncoupling of yeast mitochondria. AB - We asked whether the mitochondrial T-urf13 gene, associated with the male sterility phenotype of T cytoplasm in maize, can be expressed in Saccharomyces cerevisiae and whether this expression can mimic the effects observed in maize. We introduced the universal code equivalent of the T-urf13 gene into the S. cerevisiae nucleus by transformation and directed its translation product into mitochondria by means of a fusion with the targeting presequence from Neurospora crassa AT-Pase subunit 9. We show that expression of the universal code equivalent of the T-urf13 gene in the yeast nucleus does indeed mimic its effects in maize: respiratory growth of yeast is inhibited, respiration-deficient cytoplasmic mutants accumulate and NADH oxidation of isolated mitochondria is uncoupled. All these effects are observed only if the mitochondrial targeting peptide and methomyl or HmT toxin are present. PMID- 2259342 TI - Genetic analysis of the LexA repressor: isolation and characterization of LexA(Def) mutant proteins. AB - We report the isolation of LexA mutant proteins with impaired repressor function. These mutant proteins were obtained by transforming a LexA-deficient recA-lacZ indicator strain with a randomly mutagenized plasmid harbouring the lexA gene and subsequent selection on MacConkey-lactose indicator plates. A total of 24 different lexA(Def) missense mutations were identified. All except three mutant proteins are produced in near-normal amounts suggesting that they are fairly resistant to intracellular proteases. All lexA(Def) missense mutations are situated within the first 67 amino acids of the amino-terminal DNA binding domain. The properties of an intragenic deletion mutant suggest that the part of the amino-terminal domain important for DNA recognition or domain folding should extent at least to amino acids 69 or 70. A recent 2D-NMR study (Lamerichs et al. 1989) has identified three alpha helices in the DNA binding domain of LexA. The relative orientation of two of them (helices 2 and 3) is reminiscent of, but not identical to, the canonical helix-turn-helix motif suggesting nevertheless that helix 3 might be involved in DNA recognition. The distribution of the lexA(Def) missense mutations along the first 67 amino-terminal amino acids indeed shows some clustering within helix 3, since 8 out of the 24 different missense mutations are found in this helix. However one mutation in front of helix 1 and five mutations between amino acids 61 and 67 suggest that elements other than helices 2 and 3 may be important for DNA binding. PMID- 2259343 TI - Auxin regulates the promoter of the root-inducing rolB gene of Agrobacterium rhizogenes in transgenic tobacco. AB - The regulation in tobacco of the rolB and rolC promoters of Agrobacterium rhizogenes pRi 1855 TL-DNA was studied by using the beta-glucuronidase (GUS) reporter system in transgenic plants. A 20- to 100-fold increase of GUS activity was selectively induced by auxin in rolB-GUS transformed mesophyll protoplasts, whereas this auxin-dependent increase was only 5-fold in rolC-GUS protoplasts. Moreover, both gene fusions exhibited similar tissue-specific expression in aerial parts but different patterns in roots. The spatial pattern of rolB-GUS expression could be strongly modified by the addition of exogenous auxin, further suggesting that auxin plays a central role in the regulation of the rolB promoter in tobacco. The tissue-specific and auxin-dependent regulation of the rolB promoter is discussed in relation to the effects of the rolB gene on rhizogenesis and on cellular responses to auxin. PMID- 2259344 TI - Homologous domains of the largest subunit of eucaryotic RNA polymerase II are conserved in plants. AB - Genomic and cDNA clones homologous to the RpII215 gene of Drosophila were isolated from Arabidopsis thaliana and assigned to a single copy gene encoding a transcript of 6.8 kb. Nucleotide sequence analysis of Arabidopsis genomic and cDNAs revealed a striking homology to yeast, Caenorhabditis, Drosophila and mouse genes encoding the largest subunit of RNA polymerase II. The Arabidopsis gene rpII215 contains 13 introns, 12 of which interrupt the coding sequence of a protein of 205 kDa. The position of the first intron is conserved between plant and animal genes, while an intron located in the 3' untranslated region of the rpII215 gene is unique to Arabidopsis. Common domains present in all known largest subunits of eucaryotic RNA polymerase II were identified in the predicted sequence of the Arabidopsis RpII215 protein. Both the order and the position of N terminal Zn2+ finger and of DNA and alpha-amanitin binding motifs are conserved in Arabidopsis. The C-terminal region of the Arabidopsis protein contains 15 consensus and 26 variant YSPTSPS repeats (CTDs). Highly conserved structure among the various C-terminal domains suggests that the largest subunit of RNA polymerase II in plants may also interact with transcription factors and with protein kinases that control the cell cycle as in other organisms. PMID- 2259345 TI - Isolation and characterization of a cellulase gene family member expressed during avocado fruit ripening. AB - We present in this paper the structural analysis of two members of a small cellulase gene family, designated cel1 and cel2, from avocado. These genes were isolated by screening a lambda EMBL3 genomic library with a ripening-induced cellulase cDNA. Restriction endonuclease and Southern blot analyses showed that the cel1 gene is highly homologous to the cellulase cDNA and thus represents a ripening-related cellulase gene. The other cellulase gene, cel2, is closely related to cel1, but is divergent at its 5' end. The nucleotide sequence of a 5 kb region encompassing the cel1 gene was determined. Four previously characterized cellulase cDNAs from ripe fruit are identical to the eight exons of the cel1 gene. RNase protection and primer extension analyses were used to define the transcription start site of cel1 and to quantitate cel1 transcripts in ripening fruit. The cel1 mRNA was present at a low level in unripe fruit and increased 37-fold during ripening. Partial DNA sequence analysis of cel2 and comparison to the cel1 sequence revealed a high degree of similarity both at the DNA and deduced amino acid sequence levels. No characterized cellulase cDNAs derived from ripe fruit represent cel2 transcripts. These data suggest that the cel1 gene is responsible for a major portion, if not all, of the cellulase transcripts in ripe fruit. The DNA sequence of 1.4 kb of 5' flanking DNA of the cel1 gene was compared to the upstream sequence of other ethylene-regulated genes. Several interesting upstream sequence motifs were identified and are discussed. PMID- 2259347 TI - Molecular biology of rye-grass pollen allergens. PMID- 2259346 TI - Immunochemical perspectives of allergy: in the steps of Karl Landsteiner. PMID- 2259348 TI - House dust mite (Dermatophagoides spp.) allergens: research directions and priorities in the 1990s. PMID- 2259349 TI - Insect venom allergens. PMID- 2259350 TI - Alcohol-responsive myoclonic dystonia in a large family: dominant inheritance and phenotypic variation. AB - Alcohol-responsive myoclonic dystonia is reported in 26 individuals in a six generation family, thus indicating autosomal dominant inheritance. Twenty affected family members aged between 3 and 56 years were examined on one occasion. Myoclonus in arms, shoulder, and neck distribution was seen in 17, with occasional generalized jerks in 14. Leg dystonia/hemidystonia was seen in two infant cases, writer's cramp in seven, torticollis/retrocollis in two, and finger tremor in three. The onset of myoclonus was regularly reported from 2 to 3 years of age, the onset of leg dystonia/hemidystonia from 6 to 18 months of age, writer's cramp from early school age, and neck dystonia from late teenage. The effect of alcohol had been noted in 10 individuals, and seven of them abused alcohol. Once established, the neurological signs did not progress significantly. Leg dystonia resolved in two juvenile members. Two adult members had recovered from myoclonus: one elderly man and one posthemorrhagic spastic hemiplegic man. Extensive family investigation is necessary to clarify the clinical variation of this autosomal dominant disorder of involuntary movements. PMID- 2259351 TI - Sleep disorders and sleep effect in Parkinson's disease. AB - It has been suggested that sleep may have a positive effect on morning motor symptoms in Parkinson's disease (PD). We examined this possibility and also looked at common sleep disorders in PD. Seventy-eight PD patients and 43 normal elderly subjects answered a questionnaire. Of the PD patients, 43.6% reported improved motor symptoms in the morning, 37.2% worse, and 19.2% unchanged compared to the rest of the day. No difference was found between morning-better and -worse groups with respect to age, duration or stage of PD; antiparkinsonian medications utilized, and predominant motor symptoms. However, the morning-same group had a shorter duration of PD and less severe disease and required fewer dopaminergic medications. Sleep disorders were seen with equal frequency in the morning-better and -worse groups. Our results suggest that sleep does not have a direct effect on morning motor function. Alterations in morning motor symptomatology probably represent a manifestation of motor fluctuations. Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than controls. In addition, nocturnal vocalizations and daytime hallucinations occurred only in the PD group. PMID- 2259352 TI - Neuropathological studies in a mutant hamster model of paroxysmal dystonia. AB - Dystonic movements in a mutation of the Syrian golden hamster, named dtsz, have several features in common with clinically observed paroxysmal dystonic choreoathetosis. In this study the CNS of the mutant hamsters and age-matched nondystonic controls was examined for morphological alterations at the age of 30 days, i.e., when the severity of the dystonic syndrome is fully developed. Particular interest was directed to those brain regions (caudate nucleus, putamen, globus pallidus, ventrolateral thalamus) that are presumably involved in symptomatic dystonia of humans, as well as to regions (e.g., spinal cord, dorsal root ganglia, nucleus ruber) for which neuropathologically detectable lesions have been found previously in the dystonia musculorum mouse. The neuropathological investigation was carried out on routine paraffin histology on step sections of the whole brain and spinal cord. In addition, a silver impregnation method was used for detection of pre- and/or postsynaptic degeneration. Light microscopic examination, including morphometry, of the nervous tissue failed to reveal any morphological or morphometric differences between control and dystonic hamsters. The only abnormality that was found in several control and dystonic hamsters was hydrocephalus. Breeding studies using magnetic resonance imaging for detection of hydrocephalus showed that hydrocephalus was hereditary but not related to dystonia. Virus infections as a cause of hydrocephalus or dystonia could be excluded by serological analysis with determinations of various virus antibodies in hamster sera. The lack of neuropathological alterations related to dystonic movements in the present study in dtsz hamsters is comparable to most cases of human hereditary or idiopathic dystonia, which show dystonic movements in the absence of morphological alterations. PMID- 2259353 TI - Limb positioning and magnitude of essential tremor and other pathological tremors. AB - We examined the influence of maintaining different postural configurations of the upper extremity on the magnitude of tremor in patients with essential tremor and with postural tremor from a variety of other neurological disorders. Patients maintained postures requiring different angles of forward flexion in the sagittal plane, of horizontal flexion, and of elbow extension. The tremor of patients diagnosed with essential tremor was either unaffected or affected only little by changes in limb position. In contrast, patients with pathological tremors, of the cerebellar postural, parkinsonian, and other types, exhibited positional dependence of their tremor. When there was positional dependence of tremor, it was always largest when the hands were near the nose or chin. These observations suggest a practical method for assistance with the clinical discrimination of essential tremor from other postural tremors. PMID- 2259354 TI - Blepharoclonus and parkinsonism associated with aqueductal stenosis. AB - A 28-year-old man with a history of congenital hydrocephalus due to aqueductal stenosis shunted at 45 days of age is presented. At age 4 years the valve had to be removed because of septicemia. Twenty-three years later he developed parkinsonian signs and abnormal, involuntary rhythmic contractions of the eyelids. The latter were elicited on gentle eye closure. Parkinsonism promptly improved after ventriculoperitoneal shunting, but blepharoclonus persisted unchanged. PMID- 2259356 TI - Geographic distribution of deaths due to Parkinson's disease in Canada: 1979 1986. AB - Mortality figures for Parkinson's disease in Canada from 1979 to 1986 were examined by province and by sex. As seen in other studies, Parkinson's disease showed a statistically significantly higher prevalence in males than in females (p less than 0.01). An uneven distribution across provinces was found when mortality rates were compared by males and when males and females were grouped together. Females did not show a significant variation across provinces. Five provinces showed a higher incidence of Parkinson's disease among males than in females (p less than 0.05), whereas the other provinces showed no difference. British Columbia and Manitoba showed the highest rates for males as well as the highest rates when males and females were grouped together. The uneven geographic distribution of Parkinson's disease offers support for the possible involvement of environmental factors in the etiology of some forms of idiopathic Parkinson's disease. Suggestions for further research are outlined. PMID- 2259355 TI - Spontaneous orofacial dyskinesias in a captive cynomolgus monkey: implications for tardive dyskinesia. AB - We describe a syndrome of spontaneous orofacial dyskinesias and cage stereotypies in a singly housed adult cynomolgus monkey never previously exposed to neuroleptic drugs. Abnormal movements were readily suppressed by acute treatment with haloperidol (0.03-0.24 mg/kg i.m.) or SCH23390 (0.05-0.2 mg/kg i.m.) but not by physostigmine (0.005-0.04 mg/kg i.m.) or scopolamine (0.0025-0.04 mg/kg i.m.). The symptomatology and response to pharmacological manipulations was indistinguishable from that previously attributed to chronic neuroleptic treatment in primates. Our findings indicate that neuroleptic-induced tardive dyskinesias in most primate studies have not been clearly demonstrated. PMID- 2259358 TI - Tardive eating dystonia. AB - After cessation of long-term treatment with haloperidol, a 77-year-old man developed severe dyskinetic-dystonic movements involving mainly the tongue and associated also with oromandibular dystonia and blepharospasm that were manifested exclusively during the process of eating and that interfered with feeding. There were no spontaneous involuntary movements nor were they apparent during any other simple or complex activations of the orofacial musculature. PMID- 2259357 TI - Unilateral abolition of extrapyramidal rigidity after ipsilateral cerebellar infarction. PMID- 2259360 TI - MAO-B and Parkinson's disease. PMID- 2259359 TI - Involvement of corticospinal tract in Wilson's disease. A study of three cases with transcranial stimulation. AB - Muscle responses evoked by transcranial stimulation were studied in three patients with Wilson's disease. Abnormalities indicating involvement of corticospinal tract were demonstrated in one patient. In keeping with recent evoked potential studies, this finding suggests that lesions in Wilson's disease may affect structures other than the extrapyramidal system. PMID- 2259361 TI - Palatal myoclonus: treatment with 5-hydroxytryptophan and carbidopa. PMID- 2259362 TI - What is it? Case 1, 1990: progressive unilateral rigidity, bradykinesia, tremulousness, and apraxia, leading to fixed postural deformity of the involved limb. PMID- 2259363 TI - Multiple sclerosis occurring with paroxysmal unilateral dystonia. PMID- 2259364 TI - Head tremor after a remission of spasmodic torticollis. PMID- 2259365 TI - Writing tremor and writing dystonia. PMID- 2259366 TI - An improved method for cytogenetic analysis of meiotic aneuploidy in rodent and frog spermatocytes. AB - Methods are described for the attachment of isolated spermatocytes to glass slides and the subsequent hypotonic swelling and gradual fixation of the metaphase I and metaphase II cells. The methods minimize cell loss and cell disruption and meiotic metaphase chromosomes become spread within residual cytoplasm thus reducing artefactual chromosome loss. Metaphase II complements from mouse, rat and frog spermatocytes prepared by these procedures had relatively low frequencies of hypoploidy (0.5-1.6%). Bivalent loss was not detected in 916 metaphase I complements. Injection of 0.1 mg/kg demecolcine into mice increased the incidence of metaphase II hypoploidy 8-fold. The hypoploid and hyperploid frequencies here increased equally. The results suggest that the methods described may be useful for the analysis of mechanisms of meiotic aneuploidy including aneuploidy resulting from chromosome loss during meiosis I. PMID- 2259367 TI - Selected abstracts of the 19th annual meeting of the European Environmental Mutagen Society. 21-26 October 1989, Rhodes, Greece. PMID- 2259368 TI - Pathogenicity determinants of Candida. AB - The incidence of infections due to Candida albicans and other related species has increased in recent years. A number of factors have contributed to this, e.g. the use of a wide range of potent antibacterial and immunosuppressive therapeutic agents and the increased incidence of immune-deficiency diseases such as AIDS. Pathogenicity determinants which confer virulence on C. albicans, and other Candida species to a lesser extent, have been reviewed. These include factors related to species and strains, adherence, dimorphism, toxin and enzyme production and cell surface composition. This review clearly shows that C. albicans virulence is a function of a multiplicity of factors working jointly to overcome the host defences. A lack or debility in any of these parameters will reflect negatively on its infectivity and make it difficult for Candida to establish itself, particularly in a healthy individual. PMID- 2259369 TI - Hepatosplenic candidosis--a late manifestation of Candida septicemia. AB - Hepatolienal candidosis was diagnosed in 27 patients suffering from malignant hematologic disorders. All patients had received intensive cytostatic chemotherapy and developed septic, antibiotic-resistant temperatures during severe treatment-induced neutropenia. During neutropenia hepatic and splenic foci were not identified by imaging procedures. Foci were poorly defined histologically. Blastospores and pseudomycelia were seen in non-reactive tissue and within necrotic areas in the liver, spleen, and other organs. Only Candida species could be isolated. One to four weeks after granulocyte recovery, round liver and splenic foci were demonstrated by sonographic and CT scans. Histologically, there were necrotic areas with blastospores and pseudohyphae exhibiting different degrees of cellular border reaction. Whereas the maximum diameter of fungal foci in aplasia was 0.4 cm, these increased in size to 1.5 cm after granulocyte regeneration. PMID- 2259371 TI - Subcutaneous mucormycosis caused by Saksenaea vasiformis in a thalassaemic child: first case report in Thailand. AB - A first case of subcutaneous infection caused by Saksenaea vasiformis in an 11 year-old Thai thalassaemic boy was described. The specific diagnosis of infection was attained from microscopic demonstration of the causal agent as well as the isolation of the fungus. The patient was successfully treated by debridement of the lesion and parenteral amphotericin B. The predisposing factors, source of infection and regimen for treatment are discussed. PMID- 2259370 TI - The epidemiology of pseudallescheriasis complicating transplantation: nosocomial and community-acquired infection. AB - The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population. PMID- 2259372 TI - A case of cutaneous mucormycosis in Shanghai, China. AB - A 34-year-old female farmer suffered from localized cutaneous mucormycosis for 17 years. At the first admission, the lesion was a dull red plaque, about 7 x 9 cm in size with ulcerations, surrounded by some nodules on the dorsum of her right hand. General examination did not reveal abnormal findings except the skin lesion. Direct examination of skin scrapings in 10% KOH revealed broad, sparsely septate, branching hyphae. Histopathology showed many intradermal granulomata and microabscesses as well as mycelial elements comprising broad, distorted, ribbon like strands. Some of them were phagocytized by multi-nucleated giant cells. Cultures revealed rapidly growing yellow colonies on Sabouraud dextrose agar medium at 25 degrees C. Sporangiophores branched in sympodia and the sporangia were globose, 35-60 microns in diameter. Their walls were deliquescent, but some of them were rather persistent. Columellae were mostly globose, 12-17 microns in diameter, up to 35 microns with collars. Sporangiospores were mainly ellipsoidal, 1.5-2.5 x 3-5 microns in size, but sometimes highly variable in size and shape. The maximum growth temperature of the isolate was 37 degrees C. The pathogenic organism isolated was tentatively identified as Mucor lusitanicus, which, as far as we know, has not been reported as a causative agent of cutaneous mucormycosis. PMID- 2259373 TI - Induction of zoospore formation in Thai isolates of Pythium insidiosum. AB - Three human isolates of Pythium insidiosum De Cock 1987, the aetiologic agent of pythiosis, were induced for zoosporogenesis. The isolates were grown on Sabouraud glucose agar for 2 days before being inoculated into boiled spikelets of Axonopus compressus (Gramineae) and then into induction medium (IM). Optimum zoospore formation was demonstrated under the light microscope after incubation for 24 h at 37 degrees C in IM. PMID- 2259374 TI - Opinions differ on spending NIH gold. PMID- 2259375 TI - BSE. Maternal transmission in antelope. PMID- 2259376 TI - Cancer research. ICRF in row over 'exaggerated' claim. PMID- 2259377 TI - French fetal cell transplant operations. PMID- 2259378 TI - Research funds. Hughes reaches out. PMID- 2259379 TI - Antigen processing. Transporters of delight. PMID- 2259380 TI - Cancer. A deadly inheritance. PMID- 2259381 TI - Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons. AB - Moderate non-progressive cognitive impairment is a consistent feature of Duchenne muscular dystrophy (DMD), although no central nervous system (CNS) abnormality has been identified. Recent studies have elucidated the molecular defect in DMD, including the absence of the protein dystrophin in affected individuals. Normal brain tissue contains dystrophin messenger RNA and dystrophin is present in low abundance in the brain and seems to be regulated in this tissue, at least in part, by a promoter that differs from that in muscle. Until now, antibodies and immunocytochemical methods used to demonstrate dystrophin at the plasma membrane of mouse and human muscle have proven inadequate to localize precisely dystrophin in the mammalian CNS. We have now made an antibody (anti 6-10) which is much more sensitive than those previously available to immunolabel dystrophin in the CNS. Using this antibody, we found that in the mouse, dystrophin is particularly abundant in the neurons of the cerebral and cerebellar cortices, and that it is localized at postsynaptic membrane specializations. Dystrophin may have a different role in neurons than in muscle, and an alteration at the synaptic level may be the basis of the cognitive impairment in DMD. PMID- 2259382 TI - Cell-autonomous action of zebrafish spt-1 mutation in specific mesodermal precursors. AB - In zebrafish, as in Xenopus, the well-orchestrated cell movements of gastrulation can be dissected into several components, including epiboly, involution, convergence and extension. Embryos homozygous for the recessive lethal mutation spt-1(b104) or 'spadetail' have a complex set of defects in the trunk of the embryo that may arise secondarily after loss of one of these movements, convergence, from those precursors that would normally have given rise to trunk somitic mesoderm. We have now tested this hypothesis by transplanting cells between wild-type and mutant embryos, to identify the cells that spt-1 affects directly. Our results show that the mutation autonomously affects only those mesodermal precursors located along the lateral margin of the early gastrula blastoderm. Other mesodermal cells and all ectodermal precursors seem not to require function of the wild-type gene. Our findings reveal an unexpectedly delicate genetic control of vertebrate gastrulation. PMID- 2259383 TI - Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. AB - Class I molecules of the major histocompatibility complex (MHC) bind and present peptides derived from the degradation of intracellular, often cytoplasmic, proteins, whereas class II molecules usually present proteins from the extracellular environment. It is not known how peptides derived from cytoplasmic proteins cross a membrane before presentation at the cell surface. But certain mutations in the MHC can prevent presentation of antigens with class I molecules. In addition, mutations possibly in the MHC can affect presentation by class II molecules. Here we report the finding of a new gene in the MHC that might have a role in antigen presentation and which is related to the ABC (ATP-binding cassette) superfamily of transporters. This superfamily includes the human multidrug-resistance protein, and a series of transporters from bacteria and eukaryotic cells capable of transporting a range of substrates, including peptides. PMID- 2259384 TI - A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. AB - Major histocompatibility complex (MHC) class I molecules export peptides to the cell surface for surveillance by cytotoxic T lymphocytes. Intracellular peptide binding is critical for the proper assembly and transport of class I molecules. This mechanism is impaired as a result of a non-functional peptide supply factor gene (PSF) in several human mutant cell lines with genomic lesions in the MHC. We have now identified PSF in the MHC class II region by deletion mapping in mutants and chromosome-walking. PSF is homologous to mammalian and bacterial ATP dependent transport proteins, suggesting that it operates in the intracellular transport of peptides. PMID- 2259385 TI - Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li Fraumeni syndrome. AB - Tumour suppressor genes, whose usual function seems to be controlling normal cell proliferation, have been implicated in many inherited and sporadic forms of malignancies Much evidence supports the concept of tumour formation by loss-of function mutations in suppressor genes, as predicted by the two-hit model of Knudson and DeMars. The suppressor gene, p53, is affected in such a manner by numerous mutations, which occur in a variety of human tumours. These mutations usually represent the loss of one allele and the substitution of a single base in the other. We have now analysed the p53 gene in a family affected by Li-Fraumeni syndrome, a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites. In some instances the neoplasms seem to be related to exposure to carcinogens, including ionizing radiation. The Li-Fraumeni family that we studied had noncancerous skin fibroblasts (NSF) with an unusual radiation-resistant phenotype. DNA derived from the NSF cells of four family members, spanning two generations, had the same point mutation in codon 245 (GGC----GAC) of the p53 gene. This mutation leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53. The NSF cell lines with the mutation also retained the normal p53 allele. This inherited p53 mutation may predispose the members of this family to increased susceptibility to cancer. PMID- 2259387 TI - Primary lymphoma of bone. AB - Primary lymphoma of bone is a rare clinical entity that accounts for less than one per cent of all non-Hodgkin's lymphomas. Although they occasionally present as a solitary lesion in bone, lymphoma involving bone is a manifestation of disseminated disease in many instances. All patients initially found to have a solitary lymphoma of bone need to be thoroughly investigated for systemic disease because more than half of the patients presenting with initially solitary bone lesions are found to have systemic disease involving lymph nodes and/or other organs. Choice of therapeutic management is based on the stage of disease. Stage I-E primary lymphoma of bone can be controlled in 70-90% of cases using local radiation therapy alone if adequate radiation doses are used. Patients with advanced disease should be treated with combination chemotherapy in addition to local radiotherapy. Loeffler et al reported long-term survival results of 90% 8 year actuarial overall survival rate for children with primary lymphoma of bone who received combined therapy with radiation and chemotherapy (adriamycin, prednisone and oncovin). The actuarial lymphoma-free survival rate was 100% at eight years. Regardless of stage of the disease, radiation treatment to the primary tumor appears to be critical for adequate local control of disease as well as rapid symptomatic relief. PMID- 2259388 TI - Infrared photocoagulation of hemorrhoids. AB - Twenty five patients with grade one and grade two bleeding internal hemorrhoids were treated with infrared photocoagulation. This study did not compare the different methods of treatment, however the results do support the contention that infrared photocoagulation is an effective, safe method of treatment for low grade bleeding internal hemorrhoids. PMID- 2259386 TI - Eosinophilic fasciitis in a ten year old boy. PMID- 2259390 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 2259389 TI - Thanksgiving reflections. PMID- 2259391 TI - Inhibition of noradrenaline release by neuropeptide Y does not involve protein kinase C in mouse atria. AB - In this study, we investigated the possible involvement of protein kinase C in the inhibitory effect of neuropeptide Y (NPY) on the electrical stimulation induced release of radioactivity from mouse atria incubated with [3H] noradrenaline. The protein kinase C activators, phorbol dibutyrate (PDB, 0.001-1 mumol/l) and phorbol myristate acetate (PMA, 0.001-1 mumol/l), increased the release of noradrenaline in a concentration-dependent manner. Interestingly, the maximum effect on noradrenaline release was significantly greater for phorbol dibutyrate compared to phorbol myristate acetate. The enhancement produced by both phorbol esters was significantly reduced by the protein kinase C inhibitor, K-252a (1 mumol/l). In the presence of the concentration of either phorbol ester (PMA, 0.1 mumol/l, PDB 1 mumol/l), that was supramaximal for increasing the release of noradrenaline, NPY (0.3 mumol/l) significantly inhibited the release of noradrenaline. Moreover, in the presence of the protein kinase C inhibitors, K 252a (1 mumol/l) or polymyxin B (70 mumol/l), NPY (0.3 mumol/l) also significantly inhibited the release of noradrenaline. Therefore, it is concluded that protein kinase C is not involved in the prejunctional inhibitory effect of NPY on noradrenaline release in the mouse atria. Furthermore, since K-252a also inhibits cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and myosin light chain kinase, it is likely that these kinases are also not involved in the inhibitory mechanism of NPY. PMID- 2259393 TI - Coexistence of neuropeptides in the hypothalamic paraventricular nucleus of the sheep. AB - The chemical organization of the hypothalamic paraventricular nucleus (NPV) of the sheep was studied immunocytochemically by using antisera raised against oxytocin (OXY), ovine corticotropin releasing factor (CRF), somatostatin (SRIF), neurotensin (NT) and vasoactive intestinal polypeptide (VIP). Examination of immunocytochemically stained frozen, 30-40 microns thick, and paraffin serial, 6 microns thick, sections has shown that chemically specified subsets of neurons are not strictly demarcated anatomically and that OXY and SRIF or CRF and VIP are jointly expressed by certain subpopulations of neurons which are different from that producing both OXY and CRF. PMID- 2259392 TI - Regional distribution of cholecystokinin messenger RNA in rat brain during development: quantitation and correlation with cholecystokinin immunoreactivity. AB - The regional distribution of CCK-octapeptide (CCK) and CCKmRNA were studied in parallel in rat brain during development in order to characterize changes in gene expression in different structures at different periods of development and to determine whether differential regulation of translation and peptide turnover occurs, by correlating peptide and mRNA levels. CCK was characterized by Northern blot analysis. Methods were developed for quantitation of CCKmRNA by in situ hybridization (ISH) and compared with results obtained by slot blot analysis. Analysis of CCKmRNA by ISH showed that CCKmRNA was abundant in cerebral cortex, hippocampus, dentate gyrus, thalamus, inferior colliculus and periaqueductal grey in keeping with the high concentrations of CCK-like immunoreactivity in cell bodies located in these regions. Quantitation of CCKmRNA by computerized densitometric image analysis by reference to [35S]brain paste standards gave a similar pattern to that obtained by slot blot analysis of regional RNA extracts. Distinctive patterns of CCK development were seen. In cerebral cortex and hippocampus, a marked increase in peptide and mRNA levels was found from day 1 which showed a steady increase up to adult levels. However, in the thalamus, the highest levels of mRNA and peptide were reached at a much earlier stage, generally by 14d. In contrast, inferior and superior colliculus showed a delayed onset of peptide expression. PMID- 2259394 TI - Development of a traumatic intracranial hematoma after a "minor" head injury. AB - We have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma. Over a 10-year period, 183 patients who were able to open their eyes spontaneously, were oriented to person, place, and time, and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma. The hematoma was extradural in 54% of these patients. A history of altered consciousness or symptoms of headache and vomiting were present in 61% of the patients; 33% had a focal neurological deficit, and 43% had either focal deficit or signs of a basal skull fracture. A skull fracture was shown radiologically in 60% of patients, including 52% of those not clinically suspected of having an intracranial lesion. Six months after injury, 77% of the patients had made a moderate or good recovery. The possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted, even when there are no abnormal clinical signs, and a skull x-ray retains a useful place in the investigation of selected patients with a minor head injury. PMID- 2259395 TI - Experimental intracerebral hemorrhage: early removal of a spontaneous mass lesion improves late outcome. AB - The purpose of the present study was to determine whether early removal of an experimental intracerebral mass altered cerebral blood flow, brain water content, neuropathological findings, or neurological function 24 hours later. In three experimental series, a 50-microliter balloon was inflated within the right caudate nucleus in rats. At 24 hours after inflation, we studied cerebral blood flow by quantitative autoradiography, brain specific gravity, and qualitative histopathology by light microscopy. The animals were also assessed using a simple neurological deficit scale. In each series, half of the animals had the balloon inflated for 10 minutes (Group 1), and half had the balloon inflated permanently (Group 2). After transient inflation, there were surprisingly small differences in the blood flow between the two cerebral hemispheres at 24 hours. By contrast, in animals with permanent inflation, several indices of blood flow were significantly worse in the hemisphere ipsilateral to the balloon: the mean and median blood flow levels in the caudate nucleus; the mean blood flow in the cerebral cortex; and the area of cortex with ischemic levels of blood flow. The specific gravity was reduced in areas surrounding the site of balloon insertion after either transient or permanent inflation, and there was evidence of ischemic cell damage in all animals studied. These changes were more severe after permanent inflation, but the differences were not significant. Neurological outcome was significantly better after transient as compared with permanent inflation. The present findings contradict previous results and suggest that early removal of an intracerebral mass may have subsequent benefits. PMID- 2259396 TI - The Children's Orientation and Amnesia Test: relationship to severity of acute head injury and to recovery of memory. AB - The Children's Orientation and Amnesia Test (COAT) was developed to assess cognition serially during the early stage of recovery from traumatic brain injury in children and adolescents. The norms for the COAT, which is composed of 16 items evaluating general orientation, temporal orientation, and memory, were defined from data obtained from 146 children aged 3 to 15 years. In 37 patients with head injuries, the duration of posttraumatic amnesia, as indicated by the number of days COAT scores were in the impaired range, was significantly related to both verbal and nonverbal memory at the baseline and 6 and 12 months after injury. COAT scores were a better predictor of verbal and nonverbal memory performance than the Glasgow Coma Scale score at 6 and 12 months after the injury. This study shows that the COAT has adequate reliability and validity as a measure of the duration of posttraumatic amnesia in children and adolescents. PMID- 2259397 TI - Surgical outcome in 435 patients who sustained missile head wounds during the Iran-Iraq War. AB - Variables important in predicting the final postsurgical outcome of 435 patients who sustained missile head wounds during the Iran-Iraq War were evaluated over a 99-month period. The type of projectile, site of injury, and presence or absence of foreign material did not seem to have a significant effect on the final outcome. Of the patients with a perforating type of injury, 48.8% had a poor surgical outcome as compared with 19.9% with a penetrating type and 15.6% with a tangential type. This difference is statistically significant (chi 2 = 14.7 and 17.1, respectively; p less than 0.001). The most important factor in predicting overall outcome was the Glasgow Coma Scale (GCS) score at the time of admission. Mortality and morbidity contributing to a poor surgical outcome were noted in only 6% of patients with a GCS score at admission of 13 to 15, in 24.6% of those with a GCS score of 9 to 12, in 57% of those with a GCS score of 6 to 8, and in 65% of those with a GCS score of 3 to 5. Of the 71 patients who died, 75% had a score of 3 to 8. Perforating projectiles or those traversing two or more dural compartments were statistically significant in contributing to mortality and morbidity (chi 2 = 17.2; p less than 0.001). The incidence of focal neurological deficit was 100, 90.6, 88, and 52.2% in patients with GCS scores of 3 to 5, 6 to 8, 9 to 12, and 13 to 15, respectively. The two best predictors of mortality in this group of patients were a low GCS score and infection. PMID- 2259398 TI - Civilian gunshot wounds to the head: a prospective study. AB - Previous retrospective studies of cranial gunshot wounds have failed to determine whether aggressive field resuscitation, triage to a neurosurgical center, and early surgical intervention can improve the assumed poor outcome of these severely injured patients. Therefore, we studied 100 consecutive patients prospectively to establish a systematic approach to treatment. If the patient retained two or more neurological signs after aggressive field resuscitation/intubation, a computed tomographic scan was performed. Rapid surgical debridement was done unless the patient deteriorated to clinical brain death. The Glasgow Coma Scale (GCS) score after resuscitation was 3 to 5 in 58 patients, 6 to 8 in 8 patients, 9 to 12 in 12 patients, and 13 to 15 in 22 patients. Seventy-six computed tomographic scans and 43 craniotomies were performed. The Glasgow Outcome Scale scores showed that 60 patients died, 2 were vegetative, 6 were severely disabled, 20 were moderately disabled, and 13 had good outcomes. There were 10 postoperative deaths. No patient with a GCS score of 3 to 5 had a satisfactory outcome; however, outcome progressively improved as the GCS score increased. We conclude that all cranial gunshot patients should initially receive aggressive resuscitation. Patients with stable vital signs should be examined by computed tomographic scan. If the patient's GCS score after resuscitation is 3 to 5 and no operable hematomas are present, then no further therapy should be offered. All patients with a GCS score greater than 5 should receive aggressive surgical therapy. PMID- 2259399 TI - Median nerve somatosensory evoked potentials and the Glasgow Coma Scale as predictors of outcome in comatose patients with head injuries. AB - Median nerve somatosensory evoked potential (SSEP) grades and Glasgow Coma Scale (GSC) scores were obtained from 51 patients with head injuries within 1 week after the injury to determine the relationship of these scores, both individually and combined, to outcome scores obtained more than 6 months after the injury. SSEP grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated P22 wave form, and the conduction time through the brain (P/N13-N20 interpeak latency). SSEP responses from both sides of the brain were combined and graded from 1 to 6. The GCS was graded without the verbal component (maximum score, 10), because all patients were intubated. All patients were unresponsive to commands. Median SSEP grades correlated better with Glasgow Outcome Scale and Barthel Index scores (R = 0.57 and 0.64, respectively; P less than 0.00001) than GCS scores did (R = 0.35 and 0.37, respectively, P less than 0.00001), and combining SSEP grades and GCS scores did not improve the predictive power of the model (R = 0.57 and 0.64, respectively; P less than 0.00001). All SSEP Grade 1 patients (n = 13) either died or remained in a vegetative state. In contrast, all SSEP Grade 6 patients (n = 7) had a moderate disability or good recovery. This study demonstrates the prognostic value of early quantitative median nerve SSEP grading for patients with head injuries who are unresponsive to commands within 1 week after the injury. PMID- 2259400 TI - Surgical decompression without transposition for ulnar neuropathy: factors determining outcome. AB - Fifty-one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients. All of the patients were men with an average age of 59 years at the time of surgery. The follow-up range was between 5 and 32 months (average, 17.8 months). The disease involved the nondominant arm in 24 patients (52%) and was bilateral in 5 (11%). In 23 cases (50%), no predisposing condition could be identified, whereas 15 patients (33%) abused alcohol and 8 patients (17%) had diabetes mellitus. Fifty-seven percent of the patients helped by surgery had symptoms for less than 1 year, whereas only 30% of patients with symptoms for more than 1 year had symptomatic improvement. The relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms. Ulnar nerve conduction velocities across the elbow were 36.13 +/- 11.76 m/s in those responding to surgery and 38.97 +/- 13.91 m/s in those not responding (c = 0.06, dF = 50, P less than 0.3). A total of 37 patients showed symptomatic improvement after decompression. Simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve. In all of these cases, compression of the nerve occurred predominantly in the epicondylar groove. Narrowing of the nerve in the groove was present in 28 cases (55%); scar tissue was found adhering to the nerve in 21 cases (41%); and two pseudoneuromas were found (4%). Forty-one operations (80%) resulted in symptomatic improvement, typically noted by the patient within the first month postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259401 TI - Angiographic study of induced cerebral aneurysms in primates. AB - Five cynomolgus monkeys treated with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied repeatedly by cerebral angiography to clarify the growth process of saccular cerebral aneurysms. Repeated angiography demonstrated saccular cerebral aneurysms in three of five monkeys; two aneurysms were found 15 months and a third 12 months after the operation. At autopsy, one saccular aneurysm was found to be bilocular in shape, and the others were unilocular. Fusiform aneurysms were also observed in four monkeys. Microscopic studies revealed the walls of the saccular aneurysms were very thin and consisted of fibrous tissue. In one aneurysm, the aneurysmal sac was almost obstructed by a well-organized thrombus. No evidence of intramural hemorrhage was found in any of the saccular cerebral aneurysms. The conversion of early aneurysmal changes into saccular aneurysms was found to occur abruptly, and no consistent growth rate was noted. The multiloculation of saccular aneurysms was closely related to the size of an aneurysm. The present study indicates that a saccular cerebral aneurysm may grow abruptly from one of several different kinds of early aneurysmal changes. PMID- 2259402 TI - Shunt for bypass graft of the cavernous carotid artery: an anatomical and technical study. AB - During direct surgery of neoplastic and vascular lesions of the cavernous sinus, the intracavernous carotid artery may be injured beyond repair, or its total isolation may be necessary for surgical management of these lesions. The newly developed procedure of a saphenous vein graft bypass of the cavernous carotid artery allows re-establishment of carotid circulation. Patients with poor collateral circulation are at high risk for ischemic complications induced by the prolonged temporary occlusion required to perform the bypass graft. Optimal management of these patients is to perform the venous bypass graft for permanent vascularization while maintaining carotid cerebral circulation through an intraoperative shunt. We studied this procedure in cadavers, and three shunt types were evaluated: the external intrapetrous-supraclinoid shunt (Type A), the internal intrapetrous-supraclinoid shunt (Type B), and the neck internal carotid supraclinoid shunt (Type C). Anatomical landmarks, techniques, distances, caliber, and materials used are presented. The rationale and candidates for such a procedure are discussed. The specifications of an optimal balloon shunt are presented, and the three procedures are compared. PMID- 2259403 TI - Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) after subarachnoid hemorrhage. AB - Delayed cerebral ischemia is the major cause of death and disability in patients who initially survive an aneurysmal subarachnoid hemorrhage (SAH). In the present study, a protocol for prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) was utilized in the treatment of SAH, and the response of cerebral blood flow (CBF) was evaluated. Serial CBF measurements, f1 and CBF15, were performed using the xenon-133 inhalation technique to maximize therapy. Surgery within 24 hours of subarachnoid hemorrhage was preferred. In 43 patients with SAH, mean hemoglobin and hematocrit were lowered 3.0 +/- 0.3 g/dL and 8.9 +/ 0.5%, respectively, over the first 24 hours. Mean f1 and mean CBF15 over the same period increased 34.2 +/- 5.8% and 21.2 +/- 3.6%, respectively. The maximum mean increase in CBF was 47.2 +/- 4.7% for f1 and 30.1 +/- 3.2% for CBF15. Cerebral blood flow remained elevated during the 21 days after SAH, irrespective of neurological grade on admission, age, sex, or angiographic arterial narrowing. This is the first report of a consistent method for establishing sustained improvement in CBF after SAH. All patients managed in total compliance with the protocol remained neurologically stable or improved. Two patients developed delayed ischemia and infarction because of the inability to sustain protocol requirements. Thirty-six of the 43 patients (84%) were discharged capable of an independent lifestyle. Triple-H therapy is a safe and effective modality for elevating and sustaining CBF after SAH. In combination with early aneurysm surgery, it can minimize delayed cerebral ischemia and lead to an improved overall outcome. PMID- 2259404 TI - Hemorrhagic pituitary adenomas: clinicopathological features and surgical treatment. AB - Forty-five (9.9%) of 453 pituitary adenomas operated on between January 1973 and November 1988 demonstrated hemorrhagic changes at surgery: 24 had a blood collection, 12 had a blood collection associated with hemorrhagic necrosis, and 9 had hemorrhagic necrosis. Thirteen patients (28.9%) experienced the acute symptoms of pituitary apoplexy, whereas another 32 had an "asymptomatic" hemorrhage, that is, the clinical course was comparable to an uncomplicated adenoma. Nineteen tumors (42.2%) showed marked suprasellar extension, 8 (17.8%) showed moderate extension, and 11 (24.5%) showed slight extension; another 2 (4.4%) were laterosellar and 5 (11.1%) were intrasellar. Invasive behavior was present in 32 cases (71.1%) and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage. The incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive; therefore, we do not suggest preoperative bromocriptine treatment in this type of tumor. Two of 14 patients operated on by the transcranial route died after surgery, whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route. It proved advantageous to operate as early as possible, even during the acute phase of pituitary apoplexy. The transsphenoidal approach gave the best results, but to achieve satisfactory late results multidisciplinary treatment was necessary, namely, postoperative radiotherapy in 23 patients, bromocriptine in 12, and endocrine replacement therapy in almost all. In an average follow-up period of 6.2 years, 5 (11.1%) symptomatic recurrences were observed. PMID- 2259405 TI - Preoperative superselective arteriolar embolization: a new approach to enhance resectability of spinal tumors. AB - The extent of surgical resection of spinal tumors is frequently limited by blood loss and technical difficulty associated with the vascularity of the tumors. We report here the use of superselective percutaneous arterial embolization to reduce the rate of blood loss at the time of surgical resection and enhance resectability. The types of tumors treated were metastatic renal carcinoma, metastatic thyroid carcinoma, metastatic melanoma, and giant cell tumor of the sacrum. Two of the patients required repeated embolization and surgery for recurrent symptoms. The estimated blood loss in seven of nine procedures performed on the six patients ranged from 300 to 800 ml, after which no transfusion was required. In two procedures, extensive resection of very large tumors resulted in larger losses of blood, and postoperative transfusion was necessary. No significant complications of embolization or surgery occurred. A key factor in our embolization technique is the use of microfibrillar collagen, which allows occlusion of tumor vessels as small as 20 microns and may prevent reconstitution of the embolized vessels by collateral flow. We conclude that preoperative arterial embolization enhances the resectability of a variety of spinal tumors by reducing intraoperative blood loss. This may provide an additional benefit by reducing the risk related to postoperative transfusion. By permitting a more aggressive surgical approach, the use of preoperative embolization also has the potential to improve outcome in patients with spinal tumors. PMID- 2259407 TI - Meningiomas involving the clivus: a six-year experience with 41 patients. AB - A series of 41 meningiomas involving the clivus operated on from July 1983 to January 1990 is reported. The presenting symptoms and signs of these patients were similar to those reported previously. All the patients were evaluated by pre and postoperative thin-section, high-resolution computed tomography using soft tissue and bone algorithms. Most of the patients also underwent magnetic resonance imaging. The regions of the clivus involved by tumor were divided into upper, middle, or lower regions on the basis of anatomical landmarks. The diameter of the tumor was measured in three axes, and a tumor volume and a tumor equivalent diameter were computed to categorize tumors as small, medium, large, or giant types. There were 9 medium, 27 large, and 5 giant tumors in this series. Some simple and some complex operative approaches were employed to effect tumor removal. Large and giant tumors often required more than one operative approach to remove the tumor. Intraoperative technical difficulties included tumor consistency, vascularity, dissection from the brain stem, and vascular and cranial nerve encasement. Postoperative computed tomographic scans documented total excision in 32 patients (78%). Residual tumor remained in the clival or cavernous sinus areas. These patients were either being observed, or were treated with gamma knife radiosurgery. There was one operative death due to pneumonia (2%), and three patients (7%) suffered permanent major neurological changes, presumably due to vascular occlusions in the posterior circulation. In the follow up period, which ranged from 3 to 76 months, 2 patients (6%) with tumors that had appeared to be totally excised experienced recurrence. These patients were treated by a second operation, alone or in combination with radiation therapy. Two patients who had subtotal excisions (25%) had evidence of regrowth. In 2 patients, tumor growth continued despite gamma knife radiosurgery or external beam radiotherapy. PMID- 2259406 TI - Antimigraine treatment for slit ventricle syndrome. AB - Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures. PMID- 2259408 TI - The operative management of basilar impression in osteogenesis imperfecta. AB - Four patients with osteogenesis imperfecta and neurologically significant basilar impression have been treated over the past 8 years. The experience has resulted in changes in our therapeutic strategy for this particularly difficult problem. These cases are discussed with respect to the disease process, neurological involvement, radiological findings, and modes of surgical therapy. The errors in management as well as the success resulting from our learning experience are described. Currently, we recommend the extensive removal of the anterior bony compression by a transoral approach. This should be followed by a posterior rigid fixation that transfers the weight of the head to the thoracic spine, in an effort to prevent further basilar invagination. PMID- 2259409 TI - Entrapment neuropathy of the median nerve at the level of the ligament of Struthers. AB - The presence of a supracondylar process and Struthers' ligament is a rare congenital anomaly that may cause compression of either the median nerve, the brachial artery, or both. The authors present a case in which the supracondylar process and Struthers' ligament compressed both the median nerve and the brachial artery. This case is unusual, in that the symptoms of compression of the brachial artery increased--namely, the pulse intensity decreased and the pain increased with elbow flexion. PMID- 2259410 TI - Surgical resection of intrinsic brain stem lesions: an overview. AB - A major limitation to the effective treatment of intrinsic mass lesions of the brain stem has been the inability to clearly define the pathological anatomy radiographically. The improved soft tissue resolution offered by magnetic resonance imaging, as compared with axial computed tomography, now makes it possible not only to accurately distinguish anatomical relationships, but also to predict the pathological nature of the lesion. Accordingly, we have been encouraged to pursue a more aggressive approach to intrinsic lesions of the brain stem that appear well circumscribed on magnetic resonance imaging scan. The object of this paper is to report the successful treatment of four intrinsic lesions of the brain stem and to present an overview of the relevant published experience. PMID- 2259411 TI - Spinal hemangioblastoma, syrinx, and hydrocephalus in a two-year-old child. AB - A two-year-old child presented with an acute inability to bear weight. Radiological investigation revealed a large cervicothoracolumbar syrinx of no known cause. During investigation, acute communicating hydrocephalus developed, which required a shunt. At surgery, a small thoracic spinal cord hemangioblastoma was discovered and excised. Complete recovery with collapse of the syrinx followed. The clinical features of this rare childhood tumor and its associated effects are discussed. PMID- 2259412 TI - Carotid-cavernous sinus fistula associated with a primitive trigeminal artery. AB - Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery. PMID- 2259413 TI - Persistent primitive trigeminal artery-cavernous sinus fistulas: report of two cases. AB - Two cases of persistent primitive trigeminal artery-cavernous sinus fistulas are presented. In one case, the fistula was treated by using a two-balloon tandem technique. This method was accomplished by introducing, inflating, and detaching a silicone balloon into the trigeminal artery, thus preserving the carotid and basilar blood flow. An unusual case of a similar fistula with only contralateral exophthalmos is also reported. The relationship between this type of fistula and the presence of aneurysms on the persistent primitive trigeminal artery and the relationship with traumatic events are discussed. PMID- 2259414 TI - A detachable balloon procedure for a traumatic internal carotid-internal jugular fistula: report of a case. AB - A case of a traumatic fistula between the internal carotid artery and the internal jugular vein is reported. The fistula was treated by detachable balloon occlusion and clipping of the internal carotid artery. PMID- 2259415 TI - Esthesioneuroblastoma with intracranial extension. AB - The authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the Department of Neurosurgery in collaboration with otorhinolaryngologists. This tumor is most frequently reported as growing inside the nasal cavities, and it can extend to the paranasal sinuses. Cases presenting initially as intracranial tumors have been infrequently reported. At present, histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry. Total resection combined with radiation therapy remains the most satisfactory treatment. PMID- 2259416 TI - Cryptic osteoid osteoma of the cranium: case report. AB - Osteoid osteoma is an uncommon benign tumor of bone that rarely involves the cranium. If often causes local pain that is worse at night, characteristically relieved by aspirin, and does not correlate with the size of the lesion. The diagnosis depends on skull radiographs and computed tomography. This report describes a case in which radiographs showed nothing abnormal. The diagnosis and operative localization were accomplished with radionuclide bone scanning. Thus, the possibility of radiographically cryptic lesions must be considered in the evaluation of atypical head pain syndromes. PMID- 2259417 TI - Intracerebral solitary plasmacytoma. AB - We report a rare occurrence of intraparenchymal plasmacytoma and review the literature. The clonal nature of the neoplasm is demonstrated by immunohistochemical and molecular techniques. The importance of the latter techniques in ruling out other pathological entities is stressed. PMID- 2259418 TI - Fine surface structure of an intraspinal neurenteric cyst: a scanning and transmission electron microscopy study. AB - The case of an 11-year-old boy with an intraspinal neurenteric cyst, which recurred 8 years and 3 months after surgery, is presented. Scanning and transmission electron microscopy of the cyst epithelium revealed marked resemblance to that of the respiratory tract, despite the presence of numerous goblet cells mimicking intestine on light microscopy study. Detailed ultrastructural findings are described. PMID- 2259419 TI - Syringomyelia secondary to compression of the cervical spinal cord by an extramedullary lymphoma. AB - A case of syringomyelia secondary to an extramedullary cervical spinal cord compression by a non-Hodgkin's lymphoma is described. After radiotherapy, the syrinx was no longer seen. The pathogenesis of this type of syrinx is discussed, and the potential benefit of radiotherapy in these cases is suggested. PMID- 2259420 TI - Computer-aided intelligence: application of an expert system to brachial plexus injuries. AB - When confronted with a patient with a brachial plexus injury, how often as neurosurgeons do we consult an atlas to confirm the anatomy of the brachial plexus and then attempt to establish the location of the lesion? Similar difficulties are encountered with lumbar and sacral plexus lesions. In a project organized to assist the neurosurgeon in this time-consuming task, a computer program that can rapidly determine the site of a lesion in a brachial, lumbar, or sacral plexus injury was created. Using known anatomical pathways (37 clinically relevant upper and 20 lower extremity muscle innervations), and relying solely upon the neurological motor examination, rapid computer-assisted diagnosis is possible. When more than one final common pathway lesion occurs (for example, multiple root avulsions of the brachial plexus), possible lesion sites can be obtained. An interactive dialogue between the user and the program helps to determine the location of the lesion. The program can be run on any IBM compatible personal computer and is presented as an instrument that provides assistance in cases of complex peripheral nerve injuries, when expert consultants are unavailable. In addition, it can be used as an aid to learning and as a review of basic neuroanatomy. PMID- 2259421 TI - Hangman's fractures involving the body of C2. PMID- 2259422 TI - Tactile pattern recognition with the Optacon: superior performance with active touch and the left hand. AB - Independent groups of subjects (n = 12) attempted to identify individual digits 0 9 using active or passive touch with a vibrotactile display (Optacon II). Repeated measures were taken on the hand factor. Number recognition was superior with active touch and with the left hand. PMID- 2259423 TI - Individual analysis of laterality data. AB - Graphical and statistical analyses are presented that allow one to check for an individual subject whether the performance during a session is stable, whether the difference between the left and the right visual half-field is significant, and whether the performance is uniform over different sessions. Analyses are given for accuracy data and for latency data. Though the analyses are described for a visual half-field experiment, they can easily be adapted for other laterality tasks. PMID- 2259424 TI - Abduction, adduction and hand differences in simple and serial movements. AB - Abductive or adductive movements were made either towards single targets left or right of "home", or sequentially from target to target with various levels of advance information. In the former situation the preferred hand completed responses (movement time, MT) faster than the non-preferred, while the non preferred hand initiated them faster (reaction time, RT); these effects were in both cases stronger with harder (knob turn) than with easier (touch) responses. Abductive responses (MTs, not RTs) were faster than adductive, especially with the preferred right hand. However in the sequential task adductive responses were the faster, consistently so by MTs, while with respect to time spent motionless at each target (down time, DT) more so with the non-preferred hand, and under conditions of maximal advance information. Findings were discussed in the contexts of movement complexity, hemispatial representation, and how advance information may be utilized in the resolution of directional uncertainty. There may be an evolutionary advantage in making complex manipulative responses adductively, close to the body, while reaches are usually made abductively, to the periphery of circumcorporeal space. PMID- 2259425 TI - Semantic and phonemic priming in the cerebral hemispheres. AB - Representation of semantic and phonemic codes in the cerebral hemispheres was investigated in two priming experiments where prime and target words were independently projected to the left or right visual fields. The first experiment, using phonemic primes, confirmed the view that phonological information is not accessible to the right hemisphere. Priming effects were obtained only when the prime and target were both projected to the right visual field. The second experiment, employing category exemplars as primes, again found the left hemisphere to be the principal locus of the priming effects. The right hemisphere was unable, by itself, to activate words related to the exemplar prime. However, projection of the prime to the right visual field significantly facilitated responses to left visual field targets. The present findings support the view advanced by Drews (Neuropsychologia 25, 419-427, 1987) and Levy and Trevarthen (J. exp. Psychol., Hum. Percep. Perform. 2,299-312, 1976) that the left lexicon is structured in accordance with an hierarchy of logical semantic relationships, while the right lexicon is organized on the basis of simple associations between concepts. It is suggested, furthermore, that the patterns of semantic, but not phonological, activation invoked by a prime may be relayed between the two lexicons. PMID- 2259426 TI - Left-handedness and myasthenia gravis. AB - In two separate studies comparing the handedness of patients suffering from myasthenia gravis with matched controls, no evidence was found to support the Geschwind Behan hypothesis of an association between autoimmune disease and left handedness. Counter to prediction both studies found marginally lower incidences of left-handedness in myasthenics, and when combined with the similar result of Cosi et al. (Cortex 24, 573-577, 1988) the difference was highly statistically significant. The personality of myasthenics, as assessed by the Eysenck Personality Questionnaire (EPQ), and in particular the psychoticism scale, which has been postulated to be related to androgen levels, was not significantly different from controls. However, assessment of sex-roles using the Bem Sex Role Inventory suggested that female myasthenics were more masculine than controls. PMID- 2259428 TI - Temporal gradient in the remote memory impairment of amnesic patients with lesions in the basal forebrain. AB - Recall and recognition of premorbid public events were studied in four groups of subjects. Dementia patients showed equal losses from all time periods compared to normal controls. In contrast, two groups of amnesic patients showed extensive remote memory losses, which were most marked for the last few years prior to onset. The difference between recall and recognition was similar in the groups. The results indicate that the retrograde amnesia associated with aneurysms of the anterior communicating artery cannot be distinguished from that of amnesia with other etiologies. Implications of the finding of a temporal gradient in the retrograde amnesia of non-alcoholic amnesics are discussed. PMID- 2259427 TI - Prism adaptation and other tasks involving spatial abilities in patients with Parkinson's disease, patients with frontal lobe lesions and patients with unilateral temporal lobectomies. AB - Patients in the early stages of Parkinson's disease were compared with patients who had sustained damage specific to either the frontal or temporal lobes and normal controls on a delayed alternation task, a test of the left right orientation and a prism adaptation task. On the former two tasks age accounted for more of the variability in performance than did site of brain lesion. However, patients with frontal lobe, right temporal lobe or basal ganglia damage were significantly impaired on the adaptation task. The results are discussed with regard to "switching", "sequencing" and "internal guidance" of movement hypotheses. PMID- 2259429 TI - Fast imaging. AB - Gradient-echo pulse sequences are a valuable adjunct to the standard spin-echo sequences used for MR imaging of the brain and spine. Gradient-echo techniques enhance the signal of flowing fluids and increase the conspicuity of vascular lesions. They also increase the sensitivity of MR for chronic hemorrhage and calcification. Finally, steady-state techniques produce a myelographic effect to help evaluate degenerative diseases of the spine. PMID- 2259430 TI - 3-D imaging of the CNS. AB - 3-D gradient echo techniques, and in particular FLASH, represent a significant advance in MR imaging strategy allowing thin section, high resolution imaging through a large region of interest. Anatomical areas of application include the brain, spine, and extremities, although the majority of work to date has been performed in the brain. Superior T1 contrast and thus sensitivity to the presence of GdDTPA is achieved with 3-D FLASH when compared to 2-D spin echo technique. There is marked arterial and venous enhancement following Gd DTPA administration on 3-D FLASH, a less common finding with 2-D spin echo. Enhancement of the falx and tentorium is also more prominent. From a single data acquisition, requiring less than 11 min of scan time, high resolution reformatted sagittal, coronal, and axial images can obtained in addition to sections in any arbitrary plane. Tissue segmentation techniques can be applied and lesions displayed in three dimensions. These results may lead to the replacement of 2-D spin echo with 3-D FLASH for high resolution T1-weighted MR imaging of the CNS, particularly in the study of mass lesions and structural anomalies. The application of similar T2-weighted gradient echo techniques may follow, however the signal-to-noise ratio which can be achieved remains a potential limitation. PMID- 2259431 TI - The clinical applications of echo planar imaging in neuroradiology. AB - Ultra high speed echo-planar imaging gives an imaging time typically of the order of a few minutes, facilitating throughput, improving patient tolerance and allowing real time dynamic studies. A complete two dimensional image may be acquired in a single shot lasting between 64 and 128 ms. In echo planar imaging the whole of k-space is sampled as a continuous trajectory. By a rapidly switched Gy frequency encoding gradient, a train of gradient echoes is formed, each corresponding to a line in the k plane. Variable degrees at T2- or T1-weighting can be produced by methods outlined. High quality 128 x 128 transverse axial inversion recovery images of 5-10 mm thickness are obtained in 128 ms plus the inversion time. PMID- 2259432 TI - Cine MR in the evaluation of normal and abnormal CSF flow: intracranial and intraspinal studies. AB - Evaluation of intracranial and intraspinal CSF flow was accomplished by the use of cardiac gated gradient echo magnetic resonance (MR) technique. Normal patterns of pulsatile flow within the ventricles, cisterns and cervical subarachnoid space were established by this technique and these observations were compared to prior description of CSF flow. With systole there is downward (caudal) flow of CSF in the aqueduct of Sylvius, the foramen of Magendie, the basal cisterns and the dorsal and ventral subarachnoid spaces while during diastole, upward (cranial) flow of CSF in these same structures is seen. The relationships between the cardiac cycle and the CSF pulsations are demonstrated on both magnitude reconstruction and phase reconstruction MR images. Calculations of actual fluid velocity within CSF containing spaces can be obtained from the phase reconstruction images and holds promise for a more accurate analysis of CSF flow. In conditions which result in alterations of flow, cine MR dramatically shows either obstruction or excessively turbulent flow within the CSF pathways. The site of obstructed flow whether in the third ventricle, aqueduct, fourth ventricle, or subarachnoid space can be appreciated by changes in or absence of the normal hypointense signal. Cystic cord lesions such as congenital syringohydromyelia and posttraumatic spinal cord cysts may show pulsatile flow of CSF, a fact which can relate to progressive enlargement of these cysts. The distinction between myelomalacia and cyst formation in the cord is facilitated by the technique. Although the use of cine MR for the analysis of CSF flow is in its infancy, our experience indicates that this technique is useful in a wide range of pathological conditions including, but not limited to, conditions resulting in hydrocephalus or cystic cord lesions. PMID- 2259433 TI - Magnetic resonance: perfusion and diffusion imaging. AB - The use of magnetic resonance imaging to detect normal and pathological problems of perfusion and diffusion is reviewed. Motion sensitised spin-echo images can be used to detect changes in slow flow velocity within a voxel (intravoxel coherent motion (IVCM)) as well as intravoxel incoherent motion (IVIM) effects attributable to both diffusion and perfusion. Changes have been identified in a variety of brain diseases in the absence of changes in conventional images but the techniques are very vulnerable to motion artefact of all types. More rapid and more sensitive approaches using steady state free precision and echo-planer imaging are being investigated. Anisotropic diffusion imaging enables white matter tracts to be demonstrated within the brain and spinal cord as a function of their direction because diffusion of water across axons is much more restricted than it is along them. This technique provides a unique method for localisation of lesions and displays obvious changes in disease in which diffusion becomes less restricted. PMID- 2259434 TI - MR phase imaging and cerebrospinal fluid flow in the head and spine. AB - Motion of the cerebrospinal fluid (CSF) in and around the brain and spinal cord was examined in healthy subjects and in a number of patients with abnormalities of the CSF circulation. The pulsatile motion of the CSF was determined by spin echo phase (velocity) imaging, sometimes in combination with gradient echo phase contrast cine. Differences in flow patterns across CSF spaces were observed: flow reversal in the cerebellomedullary cistern and lumbar area relative to cervical CSF, and in the posterior versus the anterior subarachnoid space in the spinal canal. Flow communication was demonstrated in known communicating cysts or cavities. Differences in flow were also noted across spinal narrowing or block, and across the walls of a variety of cystic lesions in the brain and spinal cord. MR phase imaging of CSF flow provides pathophysiological information of potential clinical importance for the assessment of diseases affecting the CSF circulation. PMID- 2259436 TI - Sodium-23 magnetic resonance brain imaging. AB - This is a review of recent work in 23Na MR imaging. The main emphasis of recent papers has been pulse sequences that, with appropriate postprocessing, give images of the fast, slow, and intermediate components of T2 decay. The assignment of compartmental designation to the T2 component remains a problem except for homogeneous structures easily identifiable anatomically (ventricles, superior sagittal sinus, globe of the eye). Compartmental distribution of sodium is described. The predominance of the interstitial and plasma compartment, the invisibility of part of the intracellular sodium, and the difficulty in imaging the very fast T2 component of visible intracellular sodium make the usual Na spin echo image essentially an image of the interstitial and plasma space. Use of super paramagnetic iron oxide coupled to dextran as a contrast medium may help to identify the plasma compartment. Because the usual Na MR images are essentially interstitial and plasma images, our own interest is in observing functional changes in these compartments. Another proposed application is the detection of the very fast T2 component in brain tumors to aid in defining tumor grade and extent. PMID- 2259435 TI - Towards quantitative measurements of relaxation times and other parameters in the brain. AB - The nature and physical significance of the relaxation times T1 and T2 and of proton density are described. Methods of measuring T1 and T2 are discussed with emphasis on the establishment of precision and the maintenance of accuracy. Reported standards of success are briefly reviewed. We expect sensitivities of the order of 1% to be achievable in serial studies. Although early hopes of disease diagnosis by tissue characterisation were not realised, strict scientific method and careful calibration have made it practicable to apply relaxation time measurement to research into disease process. Serial measurements in patients and correlation with similar studies in animal models, biopsy results and autopsy material taken together have provided new knowledge about cerebral oedema, water compartmentation, alcoholism and the natural history of multiple sclerosis. There are prospects of using measurement to monitor treatment in other diseases with diffuse brain abnormalities invisible on the usual images. Secondarily derived parameters and notably the quantification of blood-brain barrier defect after injection of Gadolinium-DTPA also offer prospects of valuable data. PMID- 2259438 TI - MR imaging of brain surface structures: surface anatomy scanning (SAS). AB - MR imaging technique that permits direct and non-invasive visualization of brain surface structures (Surface Anatomy Scanning, SAS) was developed using the combination of long TE, long TR spin echo sequence and thick slice. Clinical trials in 67 patients with SAS showed excellent visualization of the sulci and the gyri on the lateral, occipital, frontal and parietal surfaces of the brain together with cortical and subcortical lesions. The results indicate that the SAS is useful for the localization of cortical and subcortical pathology, for the diagnosis of anomalous gyral patterns, and for surgical planning. PMID- 2259437 TI - New applications of MR contrast agents in neuroradiology. AB - Contrast enhancement has now become an integral part of MR imaging. In this paper, the current uses of contrast agents in MR imaging of both the head and spine are reviewed. In addition, new applications of contrast in MR imaging, including some more current and controversial, are also explored. PMID- 2259439 TI - Quinine causes isolated outer hair cells to change length. AB - The outer hair cells have been shown to exhibit motile properties which are likely to participate in the cochlear performance. Quinine is known to induce hearing loss as well as contraction of skeletal muscle. Isolated outer hair cells were exposed to quinine and tetracaine. This resulted in a biphasic elongation shortening response, quantitatively as well as qualitatively altered by tetracaine. These findings are in good agreement with similar studies on muscle. PMID- 2259440 TI - An electrophysiological comparison of solitary type I and type II vestibular hair cells. AB - We have studied the electrophysiological properties of enzymatically dissociated adult pigeon semicircular canal type I (chalice shaped) and type II (cylindrical shaped) hair cells using whole cell patch clamp techniques. Under current clamp conditions, type I hair cells often exhibit more hyperpolarized resting potentials than type II hair cells, and type I hair cells also have higher input conductances (measured with negative current steps) than type II hair cells. Under voltage clamp conditions, type I hair cells showed large, persistent outward currents over the range of about -70 to -50 mV, whereas, type II hair cells showed little or no current over this potential range. The persistent outward current of type I hair cells was not inactivated at a holding potential of -30mV, a potential that inactivated the rapidly inactivating, IA, and delayed rectifier, IK, currents of type II hair cells. This current probably contributes to both the resting potential and input conductance of type I hair cells. PMID- 2259441 TI - Summation of tension in motor units of the soleus muscle of the cat. AB - In the cat soleus muscle which is exclusively composed of slow motor units the discrepancy between the sum of individual tensions and the tension on combined stimulation of several motor units was found to be much less than previously reported for slow motor units of peroneus longus. In peroneus the tension on combined stimulation was systematically larger than the value predicted from the sum of individual tensions. For both muscles it was possible to reduce the difference between observed and expected values by comparing the tension on combined stimulation with the sum of tensions, not of single motor units, but of groups of units. It is concluded that whenever tension is measured for single motor units, especially slow units in mixed muscles, the values obtained may be modified by frictional forces. The size of the effect appears to vary from one preparation to the next. PMID- 2259442 TI - Interlimb coordination of stance in children: divergent modulation of spinal reflex responses and cerebral evoked potentials in terms of age. AB - EMG responses in the gastrocnemius (GM) and tibialis anterior muscles (TA) of both legs together with cerebral evoked potentials (CP), were recorded following perturbations of stance on a treadmill with split belts, in two age groups of children. Unilateral displacements were followed by ipsilateral short latency and bilateral long latency EMG responses. The CP was similar in both tasks. When displacements were simultaneously induced in opposite directions, a significant reduction in the long latency components of EMG responses occurred, while the amplitude of the CP was maximal in this condition. In the older children the CP and long latency EMG responses were larger and the short latency reflex potentials smaller in all conditions compared to the younger children. It is concluded that (1) CP and EMG responses reflect a divergent modulation of a given somatosensory input; (2) developmental changes are reflected in alterations in the amplitude of CP and EMG responses; (3) there is no evidence of transcortically mediated muscle responses. PMID- 2259443 TI - Expression of GABA-immunoreactivity by spinal motoneurons of some vertebrates. AB - Electrophysiological and biochemical investigations have shown that gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate central nervous system. However, the present study shows that some motoneurons located in the spinal cord of young chickens and adult monkeys display a GABA-like immunoreactivity. The expression of GABA immunoreactivity in vertebrate motoneurons suggests that this inhibitory amino acid is colocalized with acetylcholine and could play a role in the neuromuscular transmission. PMID- 2259444 TI - Effects of metabolic inhibitors and hypoxia on the ATP, ADP and AMP content of the rabbit carotid body in vitro: the metabolic hypothesis in question. AB - The effects of metabolic inhibitors (cyanide, antimycin) and hypoxia on the nucleotide content of the carotid body were investigated in vitro. The mean ATP content of carotid bodies superfused for 1 h in normoxic conditions was around 200 pmol/organ. Whereas metabolic inhibitors induced a decrease in ATP and an increase in AMP, hypoxia (10% O2 in N2, either 4 or 30 min) did not induce any significant change in nucleotide content. The significance of these results is discussed with regard to the metabolic hypothesis. PMID- 2259445 TI - Ketamine induces failure of the oculomotor neural integrator in the cat. AB - We studied the effect of intramuscular injection of low dose of ketamine (1 mg/kg) on the spontaneous ocular movements of the cat. Ketamine is a non competitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, which is used as an anesthetic agent in human surgery. We found that ketamine administration caused a failure of gaze holding: each saccade was followed by a centripetal post-saccadic drift. This defect was selective: the dynamics of the saccades was not altered (the amplitude/maximum velocity relationship was unaffected by ketamine at the dose of 1 mg/kg). We postulated that the observed effect was due to the fact that NMDA receptors were implicated in the network of the oculomotor neural integrator that converted activity related to the saccade (pulse signal) into activity responsible for gaze holding (step signal). PMID- 2259446 TI - Increased glutamic acid decarboxylase (GAD) mRNA and GAD activity in cerebellar Purkinje cells following lesion-induced increases in cell firing. AB - Lesions of the inferior olive-climbing fiber projection to the cerebellar Purkinje cell were produced in adult rats using the neurotoxin 3-acetylpyridine. At 7 days post-lesion, glutamic acid decarboxylase (GAD) activity in Purkinje cell axons terminating in the lateral division of the deep cerebellar nucleus was significantly increased (+58%) above control levels. GAD mRNA levels in Purkinje cell bodies from the same animals were measured by in situ hybridization histochemistry using a radiolabeled cRNA probe for GAD mRNA. GAD mRNA was significantly elevated (+42%) above control at 7 days post-lesion. Because lesions of the climbing fiber system increase Purkinje cell firing rates, the results suggest that increased Purkinje cell activity induces transcription of GAD mRNA, which in turn results in increased GAD availability in Purkinje cell terminals. PMID- 2259447 TI - Evidence for a preferential involvement of M1 muscarinic receptors in representational memory. AB - The effects of intrahippocampal injections to the M1-selective antagonist pirenzepine and the M2-selective antagonist AF-DX 116 were examined on performance of a representational memory task in rats. Although both antagonists impaired performance, pirenzepine was more potent than AF-DX 116. Pirenzepine (70.8 +/- 2.8% correct) produced a greater deficit than AF-DX 116 (83.3 +/- 0.0%) at 70 micrograms, and the deficit at 10 micrograms (83.3 +/- 2.8%) was equal to that produced by 70 micrograms of AF-DX 116. The data provide additional support for the cholinergic hypothesis of memory and new information regarding the subtypes of muscarinic receptors likely to be involved in representational memory. Based on the greater susceptibility of representational memory to the effects of pirenzepine, it is suggested that M1 receptors in the hippocampus play a greater role in memory function than M2 receptors. PMID- 2259448 TI - Effect of a synthetic norepinephrine precursor, L-threo-3,4- dihydroxyphenylserine on the total norepinephrine concentration in the cerebrospinal fluid of parkinsonian patients. AB - We studied the effect of a synthetic norepinephrine precursor, L-threo-3,4 dihydroxyphenylserine (L-threo-DOPS) on the total (conjugated and unconjugated) norepinephrine concentrations in the cerebrospinal fluid (CSF) of 6 parkinsonian patients with freezing phenomenon. The total norepinephrine concentrations in the CSF increased from 5- to 75-fold after treatment with L-threo-DOPS. The degree of increase in the norepinephrine (NE) concentrations was closely correlated to the dosage of L-threo-DOPS. The freezing phenomenon improved in 3 out of 6 patients. PMID- 2259449 TI - Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: effect of aminooxyacetic acid. AB - Kynurenic acid (KYNA) production from its bioprecursor L-kynurenine (KYN) was assessed in vivo by intrastriatal microdialysis in freely moving rats. In the absence of KYN, the extracellular concentration of KYNA was below the limit of assay sensitivity (i.e. less than 8 pmol/30 microliters). In the presence of KYN (50-2000 microM), KYNA concentration in the dialysate increased continuously to reach steady-state levels after 2h of perfusion. Introduction of the unspecific transaminase inhibitor aminooxyacetic acid (AOAA) through the dialysis probe caused a progressive decrease of extracellular KYNA, which reached dose-dependent minimal levels within 2 h. One mM AOAA caused an almost complete depletion of KYNA in the dialysate. These data demonstrate that extracellular KYNA can be assessed by microdialysis and that AOAA can be used as a tool to examine the neurobiology of KYNA in awake, freely moving animals. PMID- 2259450 TI - Serotonergic control of phrenic motoneuronal activity at the level of the spinal cord of the rabbit. AB - The role of serotonin (5-hydroxytryptamine, 5-HT)-mediated modulation of phrenic motoneuronal activity was evaluated by microapplication of 5-HT and methysergide into the phrenic nuclei of the rabbit. 5-HT facilitated phrenic nerve activity (PNA) considerably resulting in a long-lasting augmentation of the peak amplitude of integrated PNA. In contrast, the blockade of intrinsically active 5-HT by methysergide decreased PNA and led to a strong reduction of the peak amplitude of integrated PNA. MDL 72222 was ineffective. Blockade of 5-HT receptors by preceding administration of methysergide effectively abolished the effects of microinjected 5-HT. Respiratory timing was unaffected by both the agonist and the antagonist. These results suggest that a considerable portion of the facilitatory influence of caudal raphe nuclei on central respiratory activity takes place at the phrenic nuclei level. PMID- 2259451 TI - The central amygdala is involved in the conditioned but not in the meal-induced cephalic insulin response in the rat. AB - The central nucleus of the amygdala (CEA) is considered to be involved in the regulation of autonomic correlates of fear. Its involvement in the control of autonomic functions other than elicited by fear has received little attention. The effects of a bilateral electrolytical lesion of the CEA on feeding related insulin responses have been analyzed in male Wistar rats. The cephalic phase of the insulin response is a vagally mediated elevation of plasma insulin concentration during the first minute after meal onset, before any increase in plasma glucose can be noticed. This response can also be entrained to environmental stimuli. The insulin response elicited under these conditions is due to conditioning. CEA lesioning abolished the conditioned insulin response but not the early insulin elevation during the presentation of food. The CEA lesion failed to affect plasma glucose levels in both the meal-induced and conditioned test situations. To our knowledge this is the first study that shows that the CEA is also involved in the organization of conditioned metabolic endocrine responses. PMID- 2259452 TI - Effect of stimulation of the nucleus basalis of Meynert on blood flow and extracellular lactate in the cerebral cortex with special reference to the effect of noxious stimulation of skin and hypoxia. AB - Cerebral blood flow (CBF) and extracellular lactate in the parietal cortex were simultaneously measured in halothane-anesthetized rats. Focal electrical stimulation of the magnocellular nucleus of the basal forebrain (nucleus basalis of Meynert; NBM) for 10 min produced a significant increase in cortical CBF without any significant changes in extracellular lactate in the parietal cortex or in systemic arterial blood pressure (BP). Cutaneous pinching of a hindpaw for 10 min increased cortical CBF and BP, but did not influence extracellular cortical lactate. Systemic hypoxia for 10 min reducing the end-tidal O2 concentration from 18% to 6-8% produced a remarkable increase in extracellular cortical lactate. It was suggested that the increased cortical CBF following either NBM stimulation or pinching of a hindpaw was not due to metabolic changes in the cortical neurons of anesthetized rats. PMID- 2259453 TI - Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus. AB - Bath application of two different concentrations of muscarine produced two different effects on evoked responses in the dentate gyrus of rat hippocampal slices. A concentration of 1 microM muscarine did not affect the evoked population spike or excitatory postsynaptic potential (EPSP), but facilitated the induction of LTP. In contrast, a concentration of 10 microM muscarine depressed both the population spike and EPSP, but had no effect on LTP induction. The M1 muscarinic receptor antagonist pirenzepine (1 microM) blocked the muscarine induced facilitation of LTP, but had no effect on the depression of evoked responses. These data suggest that activation of M1 receptors can facilitate the induction of LTP. PMID- 2259454 TI - Increased number of unmyelinated fibers in the ventral root after peripheral neurectomy in adult rat. AB - We examined the possibility that peripheral nerve injury in the adult rat triggers sprouting of unmyelinated ventral root afferent fibers. Three to 5 months after the sciatic nerve was sectioned on one side in the adult rat, myelinated and unmyelinated fibers were counted at 3 sites along the length of the ventral root. A sciatic nerve lesion resulted in about a 3-fold increase in the number of unmyelinated fibers in the L5 ventral root. Our data suggest that a peripheral nerve lesion in the adult rat triggers sprouting of unmyelinated afferent fibers in the ventral root. No evidence was found that dorsal rhizotomy triggers sprouting of afferent fibers. PMID- 2259455 TI - Transient increase of raf protein kinase-like immunoreactivity in the rat dentate gyrus during long-term potentiation. AB - Altered levels of cellular raf proteins (products of the raf protooncogenes) have been shown in the neurons of the dentate fascia of rats in response to high frequency stimulation, with light microscopic immunohistochemistry by using polyclonal antibodies. No raf-1-like staining was seen in unstimulated tissue, while the pan-raf antibodies revealed immunoreactivity in the cytoplasm of neurons in the Ammon's horn and dentate fascia of rats and guinea pigs. The induction of long-term potentiation in the dentate fascia of freely-moving rats triggered the appearance of raf-1-like staining and increased the number of granule cells with pan-raf-like immunoreactivity. Since these proteins are serine/threonine-specific protein kinases, their appearance in long-term potentiation may indicate the activation of important cell membrane - nucleus transduction pathways. PMID- 2259456 TI - Quantitative autoradiographic changes in 5-[3H]HT-labeled 5-HT1 serotonin receptors in discrete regions of brain in the rat model of persistent dyskinesias induced by iminodipropionitrile (IDPN). AB - Chronic injections of iminodipropionitrile (IDPN) to rat cause a persistent motor hyperactivity, lateral and vertical sustained twisting movement of the neck, random circling and increased startle response. These abnormalities are similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Significant changes in 5-HT concentration and in 5-HT2 receptor density in several motor-related brain regions have been observed in IDPN-treated rats. The present quantitative autoradiographic study was undertaken to assess the possibility that IDPN may also affect 5-HT1 receptors in rat brain. IDPN caused significant increases of 5-[3H]HT binding in the oriens and pyramidal layers of the CA3 field of hippocampus. In contrast, there were significant decreases of 5 [3H]HT binding in the frontal and cingulate cortices, the olfactory tubercle, the ventromedial aspect of the caudate-putamen, the nucleus accumbens, the superior colliculus, and the lateral septal nuclei. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome. PMID- 2259457 TI - Large amounts of neocortical beta A4 deposits without neuritic plaques nor tangles in a psychometrically assessed, non-demented person. AB - An 88-year-old mentally normal woman (Blessed test score = 27) had very large amounts (397/mm2) of deposits stained by anti-beta A4 serum in the first temporal gyrus. Senile plaques and neurofibrillary tangles were lacking on sections stained with the Bodian's silver method, with anti-tau and anti-paired helical filament (anti-PHF) antibodies. The following beta A4 deposits were found in decreasing order of frequency: diffuse (64.8%), stellate (24.4%), primitive (10.2%), classic (0.6%) plaques. Compact plaques were not observed. Diffuse deposits predominated in layers I, III and IV. On the contrary, the rare classic plaques were located in layers II and III. No amyloid angiopathy was seen with Congo red stain although beta A 4 deposits were seen in vessel walls with immunocytochemistry. These data indicate that severe diffuse beta A4 deposits in the neocortex do not induce dementia. They suggest that the development of senile plaques composed of beta A4 amyloid and of degenerating neurites is not related solely to the density of the diffuse beta A4 deposits. Nor does it depend on the regional susceptibility of the nervous tissue since beta A4 deposits were seen in highly vulnerable cortical areas. Some other, as yet unknown, factors seem necessary. In addition, determination of beta A4 level in the neocortex is not sufficient for the diagnosis of dementia of Alzheimer type. PMID- 2259458 TI - Enhanced labeling of mitotic retinal cells with an intraocular [3H]thymidine injection. AB - Tritiated thymidine ([3H]Tdr) was injected either intraocularly (i.o.) or intraperitoneally (i.p.). Autoradiography showed that more retinal cells were labeled by i.o. than by i.p. injection. Controls showed that the increased number of labeled retinal cells was not related to glioblast proliferation produced by trauma from the i.o. injection. After injection of identical doses, the peak concentration of [3H]Tdr available for incorporation into DNA was about 100 times greater after an i.o. than after an i.p. injection. The effective duration of the labeling pulse in goldfish was 9 times longer for an i.o. than an i.p. injection. This study shows that i.o. delivery of [3H]Tdr is preferable to i.p. injection for efficient delivery of label to proliferating retinal cells. PMID- 2259459 TI - Quantitative distribution of descending tectal efferent cells in salamanders. AB - In salamanders of the species Salamandra salamandra, Pleurodeles waltl, and Plethodon jordani, tectal efferent neurons projecting to the bulbar reticular formation show a stereotyped distribution as revealed by the horseradish peroxidase (HRP) method. The density of these cells increases toward caudal tectal levels reaching its maximum at the isthmic region. Neurons with ipsilaterally descending axons constitute 60-87% and are concentrated in the dorsomedial and ventrolateral sector of the tectal hemisphere, with only few neurons in the intermediate part. The contralaterally descending neurons are concentrated in the lateral sector. This pattern is assumed to reflect a motor map in the coordinates of the salamander neck muscle system. PMID- 2259460 TI - 2-Chloroadenosine decreases long-term potentiation in the hippocampal CA1 area of the rat. AB - The effect of the adenosine (ADO) analogue 2-chloroadenosine (CADO) on frequency induced long-term potentiation (LTP) of the responses evoked by stimulation of the Schaffer fibres and recorded in CA1 area was studied in hippocampal slices of the rat. CADP significantly decreased LTP of the population spikes (PS) (EC50 = 0.28 microM), and LTP of the field excitatory postsynaptic potentials (f.e.p.s.p) (EC50 = 0.33 microM). These effects were reversed by the ADO receptor antagonist 8-phenyltheophylline (8-PT) (2.5 microM). It is concluded that CADO decreases LTP through activation of a xanthine-sensitive ADO receptor. PMID- 2259461 TI - Insulin immunoreactivity in the fetal and neonatal rat retina. AB - The ganglion cell layer of pre- and postnatal rat retina is positive for insulin immunoreactivity. At birth the inner nuclear layer also stains for insulin. By 5 days after birth the layers characteristic of the mature retina are demonstrable. At this time the outer nuclear layer and both limiting membranes show insulin reactivity. The lens is positive for insulin at all stages studied and the retinal pigment and choroid layers are positive after birth. These observations suggest that insulin may be important in differentiation and/or maturation of the retina. PMID- 2259462 TI - Parvalbumin immunoreactivity in the rat retina. AB - The distribution of the Ca2+ binding protein parvalbumin was studied in the rat retina with immunocytochemistry using a mouse monoclonal antibody. Specific parvalbumin immunoreactivity was identified within a subpopulation of ganglion cells and a subpopulation of amacrine cells. The topographical data provided by the present study may serve as a basis for a functional characterization of parvalbumin's role in the nervous system. PMID- 2259464 TI - Eye movement-related neurons in the red nucleus. AB - Extracellular unit activity of the parvocellular red nucleus (RN) and spontaneous horizontal eye movements were recorded in adult, nitrous oxide-anesthetized and C1 transected cats. It was found that 7.5% of the neurons of each RN were related to spontaneous horizontal saccadic eye movements. Three types of neurons were observed: (1) bidirectional neurons which increased their frequency of discharge in relation to any horizontal eye movement; (2) unidirectional neurons which altered their frequency of discharge in relation to a horizontal eye movement of a precise direction; and (3) neurons which increased their frequency of discharge in relation to the rapid phase of an horizontal nystagmus. These 3 types of neurons modified their frequency of discharge before the initiation of the eye movement. One pair of oculomotor neurons recorded simultaneously in both RN showed a significant correlation coefficient. These results suggest that the RN may contribute to the preparation or execution of horizontal eye movements. PMID- 2259463 TI - Interaction of lithium with postsynaptic inhibition in guinea pig hippocampal neurons. AB - Intracellular recording techniques were used to study the effects of Li+ on postsynaptic inhibition of CA3 neurons in guinea pig hippocampal slices. Carbachol (0.3 microM) suppressed and phenylephrine (3 microM) enhanced the hyperpolarization induced by baclofen (0.15 microM). Low intracellular concentrations of Li+ (less than 10 microM) suppressed the muscarinic blockade of the K(+)-dependent inhibition, leaving its enhancement by noradrenergic receptor stimulation unchanged. K(+)-dependent inhibition per se was not affected. At high intracellular concentrations Li+ impaired postsynaptic Cl(-)-dependent inhibition by reducing the efficacy of an outward Cl- pump. While the effect of Li+ on the modulation of K(+)-dependent inhibition may be therapeutically relevant, its action on Cl(-)-dependent inhibition may underly some toxic effects. PMID- 2259465 TI - Visualization of histamine H1 receptors in dog brain by positron emission tomography. AB - Histamine H1 receptors were visualized in the living dog brain using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The regional distribution of these carbon-11 labeled compounds in the brain corresponded well with that of the histamine H1 receptors separately determined by in vitro binding assay. The radioactivity in the brain was reduced by treatment with triprolidine (1 mg/kg), a histamine H1 antagonist. The results of our study indicate that it is feasible to visualize histamine H1 receptors in human brain using these 11C-labeled compounds and PET. PMID- 2259466 TI - Location of the suprachiasmatic nucleus grafts in rats which restored circadian rhythmicity after transplantation. AB - In Wistar male rats whose circadian wheel running activity rhythms were disrupted by bilateral suprachiasmatic nuclei (SCN) lesions, transplantation of neonatal rat SCN into the 3rd ventricle was performed. Out of 49 rats from which adequate wheel running activity records were obtained, 15 rats showed restoration of circadian rhythm starting 2 to 13 weeks (average 1 month) after transplantation. The existence of active SCN neurons in the graft was shown by immunocytochemical reactivity to vasopressin- and VIP-like substances. In all rats, effective grafts were found in the diencephalon, mostly on the wall of the 3rd ventricle. PMID- 2259467 TI - An increase in regional brain blood flow during hypertension induced by chemical inhibition of the nucleus tractus solitarius in rats. AB - Passive or neurogenic hypertension was produced by ligation of the aorta or microinjection of glutamate diethyl ester (GDEE) into the intermediate one-third of the nucleus tractus solitarius (NTS), respectively, in 44 anesthetized, artificially ventilated rats. After bilateral sympathectomy, the blood flow (microsphere method) was increased in the cerebral cortex, thalamus, and mesencephalon in a pressure-dependent manner in the face of neurogenic hypertension, as compared with the flow during passive hypertension. We speculate that some neurogenic mechanism tends to impair cerebrovascular autoregulation when afferents arising from cardiovascular receptors were blocked by GDEE within the NTS. PMID- 2259468 TI - Centrally injected neuropeptide Y (13-36) produces vasopressor effects and antagonizes the vasodepressor action of neuropeptide Y (1-36) in the awake male rat. AB - Intraventricular injections of the Y2 neuropeptide Y (NPY) receptor agonist porcine NPY (13-36) (pNPY (13-36); 25-3000 pmol) produced a dose-dependent increase (up to 14%; ED50 value of 0.3 nmol for overall effects and 0.97 nmol for the peak effects) in mean arterial blood pressure in the awake, unrestrained male rat without affecting heart rate. Furthermore, a subthreshold dose of pNPY (13 36) (25 pmol) counteracted the vasodepressor action of the parent compound pNPY (1-36) (75 pmol), which also acts at NPY receptors of the Y1 type. These results suggest that NPY receptors of the Y1 and Y2 type have opposing actions in central cardiovascular regulation. PMID- 2259469 TI - Facilitatory effect of hypothalamo-neurohypophysial tract stimulation on milk ejection frequency in the lactating rat. AB - The relative contribution of magnocellular and parvocellular neurones to the patterning of milk ejections was studied by activation of various parts of the hypothalamo-neurohypophysial tract. During suckling of anaesthetised lactating rats, electrical stimulation of the neurohypophysis/neural stalk (15 Hz, 1.5 s on/1.5 s off, 10 min) evoked an increased frequency of milk ejections as detected by intramammary pressure recording. Bilateral stimulation of the paraventricular nuclei produced a similar facilitation in the post-stimulus period, but stimulation of the supraoptic nuclei (with either low current or current sufficient to evoke peripheral oxytocin release) had no effect on the occurrence of milk ejections. These data are consistent with the hypothesis that parvocellular but not magnocellular neurones participate in the regulation of milk ejection frequency. PMID- 2259470 TI - Antibodies to fibronectin bind to plaques and other structures in Alzheimer's disease and control brain. AB - Antibodies to fibronectin (Fn) bind not only the basal lamina in Alzheimer's disease brain, but also crystal-like formations in the grey matter, senile plaques, a subset of neuronal perikarya, and large highly processed stellate formations which were both neurofilament and glial fibrillary acidic protein (GFAP) negative and which were identified at a lower frequency in non-demented control brains. PMID- 2259472 TI - Reversibility of the inhibition of acetylcholinesterase by tacrine. AB - Inhibition of bovine erythrocyte acetylcholinesterase (AChE) by 1,2,3,4 tetrahydro-9-acridinamine (tacrine) was independent of time of incubation and was partially reversed by dilution and by increased substrate concentration. It was fully reversed by dialysis. Similar results were obtained with AChE from other sources. The results are consistent with some reports in the literature, but not with others; none of these reports examined all four criteria of reversibility. The results do not explain the prolonged inhibition of AChE in vivo or the ability of tacrine to protect animals against the lethal effects of organophosphate anticholinesterases. PMID- 2259471 TI - Time course of neostigmine action on the endplate response. AB - Miniature endplate currents (MEPCs) were focally recorded in frog sartorius muscle. In the presence of 3 microM neostigmine, the amplitude of MEPCs increased, but later, after 45-60 min of treatment, a decrease of the amplitude towards the initial levels appeared. The pronounced lengthening of the falling phase of MEPCs, which accompanied the increased amplitude, suggests that at the beginning the effect is mainly ascribed to cholinesterase inhibition. The final decreased amplitude of MEPC showed a shortening of the time course instead. This suggests that also a direct effect on endplate receptors is involved. PMID- 2259473 TI - GABAB agonists modulate a transient potassium current in cultured mammalian hippocampal neurons. AB - Depolarization of voltage-clamped cultured rat hippocampal neurons from holding potentials more negative than -60 mV produced a transient outward current with the characteristics of an A-current: it was 50% inactivated at a holding potential of -85 mV and blocked by 4-aminopyridine (1 mM). In the presence of GABA or baclofen (50-200 microM), with or without bicuculline, inactivation of this current was shifted to more positive potentials so that there was little inactivation at -70 mV. Activation of the A-current was also shifted to more positive potentials by these agonists, but the voltage dependence of activation of the sodium current was unaffected. If A-currents with similar properties can influence the time course of action potentials in presynaptic terminals. GABAB agonists could make action potentials briefer by potentiating the A-current and hence depress transmitter release. PMID- 2259474 TI - A motion illusion generated by afternystagmus suppression. AB - After a period of prolonged unidirectional smooth pursuit, the tracking target is seen to drift in the opposite direction when it is stopped, even though its retinal image is stationary. If, however, the tracking target is extinguished during the post-adaptive period, the eyes continue to drift in the tracking direction, a phenomenon known as pursuit afternystagmus. It is proposed that the visual system, in an effort to maintain fixation upon the target, produces a motor signal in the opposite direction in order to offset the residual afternystagmus. The perceptual registration of this efferent signal may then produce the motion illusion. PMID- 2259475 TI - Characterization of premotor interneurones by their input patterns--application of principal component analysis to cat cervical interneurones. AB - Principal component analysis of input patterns of cat C6-C8 interneurones (300 cells) revealed that identified premotor interneurones (11 cells) activated from skin afferents and projecting to T1 motoneurones possessed a special input pattern, characterized by restricted distribution on the plane of the first (Prin 1) versus second (Prin 2) principal component (high positive values of both components). These premotor neurones were located mostly in laminae V-VI. Among other laminae V-VI cells descending in the lateral funiculus to T1 similar to such premotor neurones, there were cells distributed similarly on the Prin 1-2 plane. Further, a majority of interneurones antidromically activated from the T1 motor nucleus at low thresholds also showed a distribution on the plane similar to the premotor neurones. We suggest that premotor neurones of this input pattern constitute a major group among laminae V-VI premotor neurones projecting to T1. PMID- 2259476 TI - Endogenous GABA mediates presynaptic inhibition of spontaneous and evoked excitatory synaptic potentials in the rat neostriatum. AB - The effect of the blockade of the gamma-aminobutyric acid (GABA) uptake system on the amplitude of glutamatergic synaptic potentials was studied by using a corticostriatal slice preparation. Nipecotic acid (0.1-1 mM), a GABA uptake blocker, produced a dose-dependent decrease of the amplitude of kynurenate sensitive excitatory synaptic potentials recorded in the neostriatum following cortical stimulation. Nipecotic acid did not affect the postsynaptic responses to exogenously applied glutamate. The presynaptic effect of endogenous GABA was bicuculline-resistant and was mimicked by baclofen (0.3-3 microM). This effect was not blocked by phaclofen (0.5-1 mM). These findings show that phaclofen insensitive GABAB receptors, activated by endogenous GABA, mediate presynaptic inhibition of cortical glutamatergic inputs in the neostriatum. PMID- 2259477 TI - Target recognition and dynamics of axonal growth in the retinotectal system of fish. AB - Embryonic and regenerating retinal axons in fish are able to seek out their retinotopic target sites in the tectum. Neither a specific preordering of axons in the retinotectal pathway nor activity-dependent axon-target interactions are required for appropriate axonal targeting. Axon-target recognition appears to be predominantly mediated by positional cell surface markers. The discrimination of position-dependent differences by retinal axons in a special in vitro assay is consistent with this concept. To understand retinal axonal regeneration we have analyzed the glial cells of the fish optic nerve and the expression of growth associated cell surface molecules on the regenerating axons. The surfaces of the glial cells identified as oligodendrocytes are excellent substrates for the elongation of regenerating axons. Raising monoclonal antibodies we have found 3 cell surface proteins specific for growing axons. In the normal adult goldfish optic nerve, these proteins are only expressed by the few new axons from the newborn ganglion cells at the retinal margin. They are re-expressed on all axons during regeneration. A known cell surface molecule, NCAM, is expressed in a similar, specific spatiotemporal pattern on the fish retinal axons and may--in normal nerves--contribute to the establishment of the age-related fiber association. Whether the re-expression of NCAM and the antigens detected by the novel monoclonal antibodies are functionally involved in axonal growth and regeneration remains to be investigated. PMID- 2259478 TI - Expression of three drebrin isoforms in the developing nervous system. AB - Drebrins are developmentally regulated brain proteins which were first isolated from brains of 10-day chick embryos. They are classified into three forms, drebrins E1, E2 and A. Cloning of drebrin cDNAs revealed that each drebrin isoform is encoded in an independent mRNA. Genomic Southern blot analysis and cloning of a drebrin gene revealed that the mRNAs of three drebrin isoforms are generated by alternative RNA splicing from a single gene. Immunohistochemistry and in situ hybridization analysis of the embryonic cerebellum indicated that drebrin mRNA is first transcribed in postmitotic neurons and that there seem relations between cell migration and expression of drebrin E1. PMID- 2259479 TI - Cell surface molecule A5: a putative involvement in retinal central connection. AB - We produced monoclonal antibodies against Xenopus tadpole visual centers and obtained an antibody named A5 (MAb-A5). The antigen of MAb-A5 is a cell-surface related protein molecule (A5 antigen). Immunohistochemistry using MAb-A5 and an eye-transplantation experiment suggest the involvement of A5 antigen in specific cell recognition between retinal axons and their targets. PMID- 2259480 TI - Distribution and biochemical characterization of the INO antigen during chick neural crest cell migration. AB - The INO (inhibitor of neurite outgrowth) antibody recognizes a laminin-heparan sulfate proteoglycan complex and was isolated for its ability to functionally inhibit axonal outgrowth of peripheral neurons. Here, we examine the distribution and biochemical characteristics of INO in the early chick embryo. Because the INO antigen is sensitive to most classical fixation procedures and fixation leads to abundant nuclear staining, the antibody was directly injected into 1.5-2.5-day old embryos prior to fixation. The distribution of the injected antibody was then observed in cryostat sections by indirect immunofluorescence. Particular attention was focussed upon regions of ongoing neural crest cell migration. The INO antigen was observed along both cranial and trunk neural crest cell migratory pathways. The antigen was seen around the basement membrane surrounding the neural tube and notochord, and underneath the ectoderm and endoderm. In addition, fibrillar staining was observed in the cranial mesenchyme and in both rostral and caudal halves of the somitic sclerotome in the trunk. The distribution pattern was identical to that previously observed for laminin or heparan sulfate proteoglycan. To confirm the nature of the INO antigen, we performed immunoprecipitations of chick embryos ranging from 1.5 to 9 days of incubation. Half of each sample was digested with heparinase prior to SDS-PAGE and silver staining. In material from young embryos, bands of 200 and 180 kD (probably corresponding to the B-chains of laminin) plus two broad smears of bands at 180 150 kD and 130-85 kD were observed without heparinase digestion. Following enzymatic digestion, the 200-kD and 180-kD bands remained, while the smears disappeared and were replaced by numerous low-molecular-weight bands. In contrast to preparations from young embryos, samples taken from embryos at day 3 or beyond did not enter the 8% gel without heparinase digestion, though the banding pattern appeared identical to younger samples after heparinase digestion in the presence or absence of Ca2+. This change in the INO antigen with age could result from an increase in the heparin-side-chains attached to similar core proteins, or from an increase in the stability of the laminin-heparan sulfate proteoglycan containing complex with time. PMID- 2259481 TI - Sympathetic innervation-mediating protein. AB - The present study was performed to elucidate the mechanisms and molecular basis of specific innervation of the peripheral tissues. Chick sympathetic nerve fibers densely innervate expansor secundariorum muscle, but not skeletal muscle. When a sympathetic ganglion was cultured in collagen gel with muscle explants, the ganglion extended neurites towards two types of muscles to the same extent. Dissociated sympathetic ganglion neurons adhered firmly to the dish precoated with materials from expansor secundariorum but not to the dish precoated with those from skeletal muscle. Sympathetic nerve fibers were found densely distributed on the substrate from expansor secundariorum but not on the substrate from skeletal muscle. These results suggest that neuronal recognition mechanisms are involved in the process of selective sympathetic innervation of the expansor secundariorum muscle of the chick. The protein which caused the dense distribution of sympathetic fibers as the substrate has been purified from heart cell-conditioned medium. The most purified fraction showed a single band with an apparent molecular weight of 370,000 daltons on SDS-PAGE under non-reducing and reducing conditions. The biological activity of the protein was over 100 times higher than that of laminin. Antiserum was raised against the factor in heart cell-conditioned medium that induced the dense distribution of sympathetic fibers in culture. Addition of the antiserum to the culture medium inhibited the dense distribution of sympathetic fibers on the purified protein-substrate without affecting the general growth of the fibers. Subcutaneous injection of the antiserum into the chicks inhibited the regeneration of adrenergic fibers following 6-hydroxydopamine-induced axotomy in peripheral tissues (heart, spleen, kidney and blood vessel).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259482 TI - Selective motoneuron outgrowth from the cord in the avian embryo. AB - Selective axonal growth at a series of branching points along pathways is essential for the establishment of precise motoneuron projections. In order to reveal some of the molecules responsible for this selective axonal growth of motoneurons, I investigated the phenomenon of why motoneurons extend axons outside the spinal cord whereas interneurons do not. The analyses of immunohistology and embryonic surgery strongly suggested that motoneurons actively select to grow out from the cord and that interneurons also actively select to grow within the cord. The staining pattern of two monoclonal antibodies obtained from crude homogenate of young chick embryos were spatially and temporally correlated with motoneuron axonal growth. The antigenic molecules of these monoclonal antibodies were purified for the purpose of revealing their functions. PMID- 2259483 TI - Peripheral nerve regeneration. AB - Schwann cell basal laminae were demonstrated to serve as efficient conduits for the growth of regenerating axons in frozen nerve grafts, and in in situ freezing experiments. Regenerating axonal sprouts usually emanated from the first node of Ranvier proximal to the site of damage, and grew out along the inner surface of the basal lamina. Early growth cones contained numerous clear vesicles of about 50 nm in diameter. PMID- 2259484 TI - Nerve net formation in the primitive nervous system of Hydra--an overview. AB - Nerve net formation was examined during head-regeneration and budding of Hydra using indirect immunofluorescence on whole mounts. The nerve net was visualized with an antiserum to a neuropeptide, RFamide. The nerve net forms in two steps: the first is the appearance of ganglion cells at the regenerating tip, and the second is the appearance of sensory cells at the apex and the simultaneous disappearance of ganglion cells from the apex. The behavior of epithelial cells during head-regeneration, as defined by monoclonal antibody TS19, corresponded with nerve net formation. We examined nerve net formation in 3 morphogenetic mutants: a head-regeneration deficient mutant (reg-16), a budding deficient mutant (L4) and a multi-headed mutant (mh-1). In addition, we also examined chimeric strains which consist of the epithelial cells from the wild type and nerve cells from a mutant, and vice versa. We obtained clear evidence that nerve net formation is controlled by the environment provided by the epithelial cells. PMID- 2259485 TI - Optic nerve regeneration by peripheral nerve transplant. AB - We studied the morphology of regenerated retinal ganglion cells and their axons in adult rodents after axotomy and autologous transplantation of the sciatic nerve. Regenerated ganglion cells, backlabeled with rhodamine dextran, were of similar size to or larger than those of intact cells in control animals. Dendrites and occasionally axons as well showed abnormal morphologies in most cells, though some cells appeared quite normal. Cross-sections of the regenerated axons, observed by electron microscopy, were always attached to either the Schwann cell cytoplasm or the basal lamina. The immunoreactive structures to anti laminin antibody were quite irregular in the cross-sectioned graft and, compared with those of the intact sciatic nerve, they were generally smaller. Their appearance closely resembled that of the basal lamina in the graft observed by electron microscopy. These observations, taken together, suggest that the laminin rich basal laminae of Schwann cells are essentially important for the regeneration of retinal axons in adult rodents. PMID- 2259486 TI - Evidence for two kinds of serotoninergic fibers in the ventral horn of spinal cord of the newly hatched chick. AB - We observed two types of serotonin-positive (5-HT) fibers in the ventral horn of the lumbar spinal cord of the newly hatched chicken: the first was composed of fine 5-HT fibers, which were increased transiently in the neuropil at 1 week after hatching (transient type); the second type consisted of thick fibers, which were densely localized around motoneuron somata in the motoneuron pools innervating extensor muscles of the hip joint (adult type). Pharmacological perturbation experiments demonstrated that these two types of 5-HT fibers may have different functions: the adult type of fibers may act to maintain an erect standing posture, whereas the transient type may act to induce or facilitate dendrogenesis (or dendritic elongation) of motoneurons. Thus, we concluded that 5 HT fibers may modulate neuronal transmission and serve as a kind of inductive agent for dendritic development in the chick spinal cord. PMID- 2259487 TI - Phenotypic plasticity of grafted catecholaminergic cells in the dopamine-depleted caudate nucleus in the rat. AB - Catecholamine-producing cells were grafted in the caudate nucleus of model rats with hemi-Parkinson's disease--animals with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopaminergic pathway. Survival of the grafted cells, dopamine synthesis/release, and recovery from motor imbalance were investigated. Motor imbalance (methamphetamine rotations) recovered in more than 90% of animals by grafting of nigral dopaminergic (DAergic) cells, in 40-60% of animals by grafting of locus coeruleus noradrenergic (LC-NAergic) cells, and in 0-30% of animals by grafting of adrenal medullary cells. Many tyrosine hydroxylase (TH) positive cells survived in the host caudate after grafting of DAergic cells. A moderate number of TH-positive but dopamine-beta-hydroxylase (DBH)-negative cells survived after grafting of NAergic cells. A few TH-positive neuron-like cells survived after grafting of adrenal medullary cells. In vivo microdialysis revealed that extracellular DA recovered up to 50-80% of that of control level, and dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) up to 25-50% of those of controls in animals that showed motor recovery after grafting. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in an in-situ hybridization-autoradiographic study. Animals that received 6-OHDA lesion only or animals that received grafting but had no surviving cells showed neither behavioral nor chemical recovery. The data suggest that grafted catecholaminergic cells survive, make phenotypic plasticity, synthesize/release dopamine, and ameliorate motor function. PMID- 2259488 TI - Transplantation of embryonic olive in the climbing-fiber-deprived adult rat cerebellum: synaptogenesis on host Purkinje dendritic spines by donor climbing fibers. AB - Synaptic formation by donor climbing fibers on the host Purkinje spines was observed in our experiments. In the adult rat cerebellum where the inferior olive and climbing fibers had been destroyed by intraperitoneal injection of 3 acetylpyridine, the medullary embryonic 14-16-day (E14-E16) tissue containing the olive was grafted. After 3 weeks, climbing-fiber-type preterminals bearing closely-packed round vesicles were found that established synaptic contacts on dendritic spines of the host Purkinje cells. Quantitative analysis indicates the increment of newly-formed climbing presynaptic terminals, the number of which was statistically significant (P less than 0.01). PMID- 2259489 TI - Cadherin-mediated cell-cell adhesion and neurogenesis. AB - Cadherins constitute a molecular family which confers adhesive specificities on cells. Their expression is spatio-temporally regulated in embryos and the multiple types of cadherins are expressed in the nervous system. The inhibition of cadherin action with antibodies resulted in the perturbation of the histogenesis of neural tissues. The sites for determining the binding specificities of cadherins reside in their amino terminal 113 amino acid region. Possible roles of cadherins associated with these properties in neurogenesis are discussed. PMID- 2259490 TI - Diagnosis and management of urinary incontinence due to detrusor instability. PMID- 2259491 TI - Is medicine becoming too fragmented? PMID- 2259493 TI - Firefighter fights mandatory AIDS testing. PMID- 2259492 TI - Help handling the hassle factor. PMID- 2259494 TI - AIDS: the new risks. PMID- 2259495 TI - Living wills: a special report. PMID- 2259496 TI - The medical silence is deafening. PMID- 2259497 TI - Polishing the apple: an age-old look at improving physician image. AB - The human tendency is to think that things were always better in the past. Recently, however, this author came across a book that shed some interesting light on those years gone by... PMID- 2259498 TI - Are you heeding malpractice warning signals? AB - Patients and attorneys often send out warning signals prior to filing a malpractice lawsuit. Be aware of the signals and learn how best to handle them. PMID- 2259499 TI - Recent developments in the management of epileptic seizures. PMID- 2259500 TI - Minimum care standards for epilepsy for Ohio. Epilepsy Standards Subcommittee, Medical Advisory Committee of the Bureau for Children with Medical Handicaps, Ohio Department of Health. PMID- 2259501 TI - Injuries of the external ear. AB - Ear injuries occur in people of all ages but predominate in active people such as wrestlers, boxers, and bike riders. The types and extent of injury are a function of the force causing the injury. Shearing forces of moderate intensity cause hematoma formation, whereas greater force causes lacerations or even amputation. Sharp objects cause lacerations determined by the force, direction, and point of impact. The high ratio of surface area to mass makes the auricle vulnerable to extremes of temperature. People participating in high-risk activities should wear protective headgear. The goal of treatment is to restore the normal contours while preventing infection. Hematoma results in disfigurement by organization or chondritis. Evacuation and pressure dressings using sterile technique correct the condition. Second-degree burns are treated by regular cleansing and application of topical antimicrobials. Deeper burns require debridement, biologic dressings, or burying the cartilage subcutaneously for later reconstruction. Simple lacerations are closed under aseptic technique using either skin-to-skin sutures only or sutures of the skin combined with intercartilage sutures. Extensive and complex lacerations require meticulous care to match all fragments and prevent infection or loss of tissue. Bare cartilage must be covered with vascularized tissue. The treatment of total amputation is controversial. Some advocate reattachment as a composite graft using intravenous low molecular weight dextrans and heparin as adjuvants. Mladick dermabrades the amputated pinna, reattaches it with sutures, and then slips it into a pocket of elevated postauricular skin for 2 weeks. Others urge microvascular reanastomosis of the small nutrient vessels. Brent and Byrd separate the cartilage from its overlying skin and envelope it first with vascularized temporoparietal fascia and then a split-thickness skin graft. Chondritis is the most feared complication of injury or surgery of the pinna. It is an aggressive process, and prompt removal of pus and necrotic cartilage is required. Exteriorization and removal of all cartilage is effective but disfiguring. Removal of only affected cartilage and constant irrigation with antibiotic solutions is effective but requires prolonged hospitalization. Iontophoresis of antibiotics into the auricle may be effective and conserve tissue. Traumatic deformities are corrected with composite grafts from the opposite ear, costal cartilage, and local pedicled flaps.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2259502 TI - Concepts of soft-tissue trauma repair. AB - The proper evaluation and treatment of soft-tissue trauma to the face is extremely important because of the psychologic, cosmetic, and functional sequelae that can occur from these injuries. The facial trauma surgeon should have a wide armamentarium of techniques to manage soft-tissue facial trauma and should approach the repair in a meticulous and scientific fashion. Although the best possible repair of the acute trauma is the goal, it is usually necessary to perform later some camouflage or revision procedures on the scar because of the high likelihood of hypertrophic scarring or inappropriate healing in the trauma scar. PMID- 2259503 TI - Facial plastic surgery. PMID- 2259504 TI - Local anesthesia for soft-tissue surgery. AB - The use of local anesthetics in soft-tissue facial surgery can be safe, efficient, economical, and convenient. Understanding these agents and using them with proficiency allows the surgeon to perform a variety of operative procedures with minimal anesthetic morbidity on patients who are relaxed, comfortable, and insensitive to pain. PMID- 2259505 TI - Mohs micrographic surgery. AB - Mohs micrographic surgery is a versatile technique for the treatment of nonmelanoma skin cancers, especially recurrent, invasive, or infiltrating basal cell carcinomas. It provides unsurpassed cure rates by using 100% surgical margin control, and it achieves maximal preservation of normal tissue. At the conclusion of tumor extirpation, the defect is ready for immediate reconstruction. With better understanding of the Mohs micrographic surgery technique, it can be more effectively used as part of a coordinated multidisciplinary approach to the treatment of patients with difficult cutaneous and paracutaneous neoplasms. PMID- 2259506 TI - Incision planning and basic soft-tissue surgery. AB - Incisions in the head and neck region need not result in unsightly scars. For open incisions, use of the RSTL or skin creases, along with good soft-tissue technique and attention to detail on closure, will yield excellent cosmetic results. PMID- 2259507 TI - Z-plasty. AB - Z-plasty is one of the oldest plastic surgery techniques. Z-plasty is a basic technique that has numerous applications in plastic surgery of the head and neck. The principles of Z-plasty are reviewed, and variations in the basic principles are explored. PMID- 2259508 TI - Skin grafts. AB - The techniques of partial-thickness and full-thickness skin grafting are reviewed, including choice of donor site, preparation of recipient site, graft harvesting, and postoperative dressings and care. A review of the basic principles of skin graft healing is included to increase understanding of the reasons these techniques are used and to show how to avoid complications associated with skin grafting. The areas of usefulness of skin grafts are discussed in relation to the face, head, and neck. PMID- 2259509 TI - Design of local skin flaps. AB - Design of the optimal local skin flap to repair a specific facial defect requires an understanding of the geometry of the various flaps, local facial anatomy, and the biomechanics of skin and soft tissue. The creative integration of these variables is one of the most challenging areas of facial plastic surgery. This article discusses some general principles of flap design with emphasis on the importance of skin tension and its distribution in preventing complications and maximizing the use of local tissue in difficult reconstructive situations. PMID- 2259510 TI - Regional flaps in facial reconstruction. AB - Soft-tissue defects of the head and neck that are too extensive to be reconstructed with local flaps without excessive impairment of either form or function usually require repair by some type of regional flap. Selection of a specific regional flap depends on the type of defect, i.e., its size and location, and on the intrinsic properties of the regional flap. Single pedicle peninsular or island axial pattern flaps are usually selected because of their improved blood supply compared with random flaps. For most skin defects of the face and neck requiring reconstruction with a regional flap, a medially based deltopectoral flap is usually preferable to musculocutaneous flaps because it is less bulky and produces less donor-site functional impairments. Likewise, for large defects of the upper or lower lip, a deltopectoral flap in most instances is the regional flap of choice for reconstruction. Nasal defects that require regional flaps for repair are reconstructed with various types of forehead flaps. The median flap remains the most useful because the donor site can be closed primarily, leaving a thin midline scar that is camouflaged relatively easily. For nasal defects that require a longer flap that can be provided by a median flap, the oblique forehead flap provides additional length sufficient to reach the base of the columella. Larger defects of the oral cavity and oral pharynx usually require regional or microsurgical flaps for reconstruction of soft-tissue deficits. In addition, mandibular reconstruction may be necessary. The pectoralis major musculocutaneous flap is the author's preferred choice of a regional flap for reconstruction of such defects. The flap readily reaches the oral cavity and oral pharynx and the muscle provides good coverage of the carotid artery when neck dissection has been accomplished. A great advantage of the flap is the ability to achieve reconstruction in one stage without the need for a controlled salivary fistula. Although the deltopectoral flap is the author's preferred regional flap for reconstruction of major defects of the hypopharynx, the pectoralis major musculocutaneous flap is the regional flap of choice when patients are severely malnourished or cachetic. Both flaps provide a source of nonirradiated skin and provide sufficient tissue for total reconstruction of the hypopharynx and cervical esophagus. Both methods of reconstruction, however, have a relatively high rate of stenosis of the distal anastomoses. PMID- 2259511 TI - Chemical face peeling. AB - The author reviews his approach to the use of phenol for chemical face peeling. A discussion of preoperative, intraoperative, and postoperative care is included. Indications, benefits, and possible complications of the procedure are discussed. PMID- 2259512 TI - Scar revision and camouflage. AB - The successful revision and camouflage of facial scars is as much an art as a science, and the best teacher is continued experience; however, common sense, a broad knowledge of available options, technical ability, and patience are all necessary if one chooses to practice in this challenging field. Patients with facial scars are vulnerable in a way that few others are, and it is the responsibility of the facial plastic surgeon to evaluate these patients properly and realistically, to prepare them for a process that may involve multiple procedures, and to see them through this process with all the expertise and compassion possible. If this is done, the rewards to the patient and to the surgeon can be immeasurable. PMID- 2259513 TI - Reconstruction of the lip. AB - The lip has important sensory and motor functions. The principle functions of the lip relate to its abilities as a sphincter that is modified by the many muscles of facial expression. The best repairs of the lip respect natural anatomic lines and preserve or restore the orbicularis muscle. When feasible, it is best to reconstruct labial defects with tissue from within the lip. As the need for replacement with extra-labial tissue becomes greater, lip reconstruction will require a more carefully selected compromise. PMID- 2259514 TI - Conceptual approach to eyelid reconstruction. AB - A variety of techniques are available to repair congenital, traumatic, or surgical eyelid defects. The unique functional requirements of the orbital tissue must be considered when choosing the most ideal surgical procedure. It is essential to preserve conjunctival integrity and eyelid closure to maintain corneal protection. Full eyelid mobility should ideally be restored. These goals can generally be achieved with the correct closure of small eyelid defects. Larger deficits are usually best replaced by the use of grafts and flaps developed from the orbital region because this tissue most closely matches the functional needs of the eye. Close ophthalmic follow-up is necessary in the postoperative period to monitor and treat any ocular complication. PMID- 2259515 TI - Threats and bets. PMID- 2259516 TI - A different sort of animal: doctor-owned company. PMID- 2259517 TI - A definition of sanctions. PMID- 2259518 TI - In memoriam: Dr. Karl A. Menninger. PMID- 2259519 TI - Medical resources and rationing. PMID- 2259520 TI - Medical schools fall short of U.S. needs. PMID- 2259521 TI - The cost of AIDS: who will pay? PMID- 2259522 TI - Dialogue with nursing. The Coalition of Pennsylvania Nurses. AB - This opportunity for Pennsylvania physicians and nurses to communicate opens the door to collaborative, goal-oriented activity in this critical stage in the evolution of health care. The invitation to speak with physicians is one avenue to share ideas about unified nursing activity, critical issues, and future trends in nursing care. This article may stimulate reaction, thought, and further dialogue with the Pennsylvania Medical Society. Pennsylvania Medicine may provide the medium for a new beginning to long-term communications and concerted action on issues addressing both nursing and medical professions as we work toward meeting health care needs of the citizens of the Commonwealth. PMID- 2259523 TI - The value of a professional recruiter. The Health Care Group. PMID- 2259524 TI - [The taxonomic aspects of the transmission of the causative agent of Lyme disease]. AB - According to world literature data 17 species of ixodid ticks have been studied for natural infection with the Lyme disease agent. Analysis of the data on the level of the infection, transovarial and transphase transmission has shown that main biological vectors of Borrelia burgdorferi are the species of the subgenus Ixodes s. str. - I. ricinus, I. persulcatus (Eurasia), I. dammini, I. pacificus (North America). Potential vectors are I. scapularis, I. dentatus, Amblyomma americanum, Dermacentor variabilis. Single isolations were registered for I. neotomae, Haemaphysalis leporispalustris, D. occidentalis. Nonidentified spirocheta was isolated from A. americanum, D. variabilis, D. parumapertum, Rhipicephalus sanguineus. No agent was isolated from I. cookey, D. albipictus, R. reticulatus, H. concinna. On the basis of comparative and ontogenetic data the species from a group of main vectors: I. ricinus, I. persulcatus, I. pacificus had been attributed by me to the phyletic group persulcatus before Lyme disease was discovered and its causative agent isolated. The question whether I. scapularis belongs to the group persulcatus was also discussed at that time but left open due to somewhat aberrant structure of gnathosoma at preimaginal phases (Filippova, 1969, 1971, 1973). 6 Palaearctic, 2 Indomalayan and 3 Nearctic species were referred to the group persulcatus at the time. I. dammini was described later, in 1979. Gnathosoma of its preimaginal phases has an intermediate structure between I. scapularis and other species of the group persulcatus. Sexually mature phase and nymph of I. dentatus have much in common with Palaearctic members of the group, I. pavlovskyi, I. kazakstani, I. kashmicus. Preimaginal phases of I. scapularis and nymph of I. dentatus were studied by me on the collection material. Thus, it is possible to speak of the belonging of main vectors of B. burgdorferi to a common phyletic group within the subgenus Ixodes s. str. and, therefore, of common origin of ecological medium for the agent. At the same time each species of the vector is an evolutionally developed difference of ecological medium for B. burgdorferi. Roots of the group persulcatus could originate as far as in Paleocene before the land connection between North America and Europe disappeared. Conditions for the existence of recent species, however, appeared considerably later and their flourishing is dated by Pliocene. The main epidemiological role belongs now to I. ricinus, I. persulcatus, I. dammini, I. pacificus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2259526 TI - [The population and genetic relationships in the bream-Digramma interrupta system (pl.) (Cestoda: Ligulidae)]. AB - It was established that host individuals, characterized by a high stability of development, play the main part in the functioning of bream-D. interrupta system. Heterozygous breams turned out to be more stable to the effect of pleurocercoids than homozygous ones. Genetically determined characters of bream infection with pleurocercoids of D. interrupta have been revealed. Mechanism of population genetic relationships in this parasitic system is discussed. PMID- 2259525 TI - [The structure of the cercarian tegument of microphallid trematodes]. AB - The tegument of mature cercariae of Microphallus sp. Podlipajev, 1979, M. claviformis, Levinseniella brachysoma and Maritrema subdolum consists of the outer syncytial layer filled with several types of secretory inclusions. Cytons and subtegumental cell ducts are absent. Covers of Microphallus cercariae have structure typical of larvae of trematodes. The tegument surface of L. brachysoma cercariae carries lamelli, spines are divided into two parts: short massive body sharpened at fore end and long thin stalk connected with basal membrane. The tegument surface of M. subdolum larvae forms tongue-like protrusions, modified spines serve as their frame. The development of tegument of the above species during cercaria morphogenesis has been traced. It is shown that at first in embryos syncytial lamina of the tegument is formed. Within it rudiments of spines have been detected as narrow transversal columns of mediate electron density. Henceforward syncytial layer has thickened, provisional spines have become conical, their matrix has become fibrous. Then the joining of protrusions of subtegumental glandular cells to outer syncytium has begun. These cells have been arranged into three types depending on the character of secret produced. The spines have acquired the species-specific structure. In members of the genus Microphallus they have become massive, and both in L. brachysoma and M. subdolum they have lengthened and subdivided into body and stalk. Spines of M. subdolum have flattened appreciably, their bodies have been found within tegumental tongue like protrusions. PMID- 2259527 TI - [Factors determining the localization of ectoparasitic isopods of the fam. Cymothoidae on the body of fish]. PMID- 2259528 TI - [Further comment on the role of sugars for the successful infection of blood sucking Diptera by protozoa that are the causative agents of human diseases]. AB - Possible reasons of a successful development of Plasmodium gallinaceum in Aedes aegypti, which were not given sugar feeding, are analysed. Such reasons are assumed to be high contents of sugars (up to 200 mg/% in the blood of chickens donors) and retention of sugar in the crop of mosquitoes, which were fed from a tampon, in control. PMID- 2259529 TI - [A finding of larvae of Fannia flies in the prepupa of the ox warble]. PMID- 2259530 TI - [Little-studied parasitic strongylid larvae (Nematoda: Strongylidae) in horses]. AB - Parasitic larvae of 30 strongylid species of horses out of 53 species known for the fauna of the USSR are identified. The paper presents descriptions of 7 earlier unknown phenons of parasitic late 4th-stage larvae, the specific belonging of which in not yet ascertained. The possibility of their identification is discussed. PMID- 2259531 TI - Protecting patients from HIV infection: is isolation an option? PMID- 2259532 TI - A pediatrician's view. PMID- 2259533 TI - Emergencies in pediatrics and the child in the emergency medical services system. PMID- 2259534 TI - Recognition and stabilization of the critically ill or injured child. PMID- 2259535 TI - Pediatric trauma: initial evaluation and stabilization. PMID- 2259536 TI - Treatment of the dehydrated child. AB - Dehydration is a potential life-threatening event to the child and requires early recognition and correction. Precise fluid management and follow-up is essential. PMID- 2259537 TI - Overwhelming infections in infants and children. AB - Infections in children may present with nonspecific findings, requiring early recognition and stabilization. Age, etiology, immunocompetency, and duration of illness should all be considered in the initial assessment. Antibiotics and aggressive support are mandatory to avoid deterioration and severe morbidity or death. PMID- 2259538 TI - Current issues in pediatric and adolescent endocrinology. PMID- 2259539 TI - Growth hormone for short stature not due to classic growth hormone deficiency. AB - The advent of recombinant DNA technology has resulted in potentially unlimited supplies of growth hormone. Sufficient quantities are now available not only for the long-term, uninterrupted treatment of GH-deficient children but potentially for the treatment of non-GH-deficient patients with other short stature or growth attenuating disorders. Short-term studies have demonstrated an improvement in the growth rates of subjects with isolated short stature, Turner syndrome, and chronic renal failure; and additional studies are under way to assess the efficacy of GH therapy of other short stature syndromes. However, the long-term efficacy and possible adverse effects of GH treatment in these situations is not known. Until there has been more experience, GH deficiency should remain the primary indication for GH treatment. Growth hormone should not be considered routine therapy for other conditions associated with or resulting in short stature. However, research should continue in these areas to define which children may benefit from GH treatment. PMID- 2259540 TI - Hyperthyroidism in children and adolescents. AB - Hyperthyroidism in infants and children usually is caused by Graves' disease; however, several other diseases can also produce hyperthyroidism in these age groups. Because the pathophysiology and clinical course of these conditions differ, optimal treatment depends on precise diagnosis. PMID- 2259541 TI - Euthyroid low thyroxine (T4) and triiodothyronine (T3) states in prematures and sick neonates. AB - This article reviews the ontogenesis of thyroid system function in the human fetus and newborn and characterizes thyroid function in the premature infant. Thyroid function disorders associated with neonatal adaptation and illness also are reviewed; these include transient hypothyroxinemia, transient primary hypothyroidism, and the syndrome of nonthyroidal illness. PMID- 2259542 TI - The Cushing syndromes. AB - The 10 years since this journal's last review of CS have seen extraordinary advances in our understanding of many aspects of its causes, diagnosis, and treatment. The spectrum of what are now called the Cushing syndromes has expanded considerably to include CD, multiple sources of ectopic ACTH secretion, and an apparent autoimmune cause. Improved assays of ACTH and the availability of CRF have provided new insight into the physiology and pathophysiology of the HPA axis and new tools for diagnosis of CS, especially in combination with selective catheterization and sampling. New imaging technology has improved our visualization of pituitary adenomas and has provided powerful methods for identifying tumors ectopically secreting ACTH and primary adrenal tumors. Finally, the refinement of transsphenoidal surgery and its success in treating CD have provided a safe and effective therapy for this disease. For those occasional patients who require medical therapy, drugs are available that decrease steroid biosynthesis. We now have a much better understanding of a fascinating disease process and are able to diagnose and treat it more correctly. One is impatient to see which new pieces of this puzzle will fall into place over the next ten years. PMID- 2259543 TI - Hyperandrogenism in peripubertal girls. AB - Androgens arise from either adrenal or ovarian secretion or by peripheral conversion of secreted precursors. The adrenals and ovaries normally contribute about equally to testosterone and AD production. DHAS is the major adrenal 17-KS. Testosterone is the major circulating form of androgen. More than 96% of plasma testosterone is bound to SHBG; the free testosterone seems to be the bioavailable fraction. Hyperandrogenism must be considered in any girl with premature or excessive development of public hair or acne, menstrual irregularity (whether it be oligo-amenorrhea or dysfunctional uterine bleeding), or obesity. The most common cause of premature public hair development (pubarche) is premature adrenarche. The most common cause of hyperandrogenism presenting in a teenage girl is polycystic ovary syndrome. However, the differential diagnosis includes "exaggerated adrenarche," late-onset congenital adrenal hyperplasia, virilizing tumors, Cushing's syndrome, hyperprolactinemia, acromegaly, and abnormalities of androgen action or of metabolism. The plasma free testosterone is a more sensitive indicator of hyperandrogenism than is the total testosterone concentration. The pattern of response of plasma free testosterone, DHAS, and cortisol to dex-suppression testing is diagnostic of the source of androgen excess. Most hyperandrogenic adolescents will be found to have PCOS. The treatment is chosen according to particular symptoms, such as menstrual irregularity, hirsutism, or obesity. PMID- 2259544 TI - Primary and secondary testicular insufficiency. AB - The possibility of testicular insufficiency is a common problem for the pediatric practitioner. Presentation varies with the severity of the defect, the developmental age achieved before onset, and the presence of associated other abnormalities. Most commonly, primary and secondary testicular insufficiency present at the time of puberty, but the presentation may be at birth or in the early neonatal period. Appropriate investigations may uncover the diagnosis at the time and allow intervention later at the appropriate age. Secondary testicular failure, although more difficult to diagnose and to differentiate from simple delay of development, offers the possibility of later development of spermatogenesis and the attainment of fertility through the use of gonadotropins or GnRH replacement programs. In primary testicular failure, because it implies an intrinsic abnormality of the functioning elements of the testis, spermatogenesis is not inducable by hormonal stimulation. Treatment of testicular failure in the neonatal period is unnecessary unless micropenis is associated. In the pubertal boy, testosterone replacement is the treatment of choice and should be initiated carefully, taking into consideration the age of the subject, his bone age, and the psychosocial circumstances. The goal of therapy is to achieve a normal progression of physical changes of puberty to physical maturity and the normal potential for sexual function. PMID- 2259545 TI - Adolescent gynecomastia. Differential diagnosis and management. AB - Gynecomastia signifies a transient or permanent disturbance in steroid hormone physiology and occurs when the male breast is exposed to a decreased ratio of androgen to estrogen. This article discusses pubertal and pathologic gynecomastia, diagnostic approach, and treatment. PMID- 2259546 TI - Disorders of sexual differentiation and development. Psychological aspects. AB - Children with abnormalities in sexual differentiation and development can have a smooth course of psychosocial development in spite of the significant risks and challenges they face. Chances for a positive emotional outcome are made more likely by the careful handling of these patients at the time of first presentation. Parents' unambiguous acceptance of the child's sex of rearing and early surgical intervention to normalize the child's external genital appearance are critical elements in a positive outcome. Further, the patterns of behavior documented in the materials reviewed in this article suggest difficulties of immaturity and social development rather than significant psychopathology. Parent child interactions were repeatedly found to be central to the child's emotional well-being, underscoring the need to provide parents with adequate counsel and support. These patterns, however, represent findings across groups of patients and cannot predict the emotional, social, or academic functioning of any individual. Within all these clinical syndromes there is great individual variation in social, emotional, and physical presentation. Finally, rather than minimizing problems, physicians need to educate parents so they can be active advocates for their children in the educational and social arenas. PMID- 2259547 TI - Turner syndrome and its variants. AB - Turner syndrome is suspected in females with short stature, gonadal dysgenesis, and lymphedema; however, there are no pathognomonic features of Turner syndrome, and the disorder should be considered in any girl with short stature or delayed puberty. This article discusses the natural history of Turner syndrome and complications that occur in various organ systems; it reviews the physical features and complications seen with various karyotypic changes in Turner syndrome. Age-specific screening and therapies are covered. PMID- 2259548 TI - Disorders of calcium and phosphorus homeostasis. AB - Calcium and phosphorus are, respectively, the fifth and sixth most abundant elements in the body; both play vital roles in a multitude of physiologic systems. Because the great bulk of these elements is found in the skeleton, a large part of the discussion of calcium and phosphorus metabolism focuses on skeletal disorders, the impact of which falls heavily on young children. This article reviews the physiology of calcium and phosphorus, the skeletal and systemic consequences of disorders of vitamin D nutrition and metabolism, and the metabolic bone disease of prematurity. PMID- 2259549 TI - Can insulin-dependent diabetes mellitus be cured or prevented? A status report on immunomodulatory strategies and pancreas transplantation. AB - The past decade has brought advances in our undestanding of the etiology of beta cell destruction leading to insulin-dependent diabetes mellitus. Most patients have an autoimmune process that begins months or years prior to overt disease. There are now reliable techniques to monitor the inflammatory process, with increasingly accurate methods for predicting disease in susceptible individuals. This information should lead to new techniques that will cure or possibly prevent diabetes. PMID- 2259551 TI - Gas exchange in HMD--an old problem with no new solutions? PMID- 2259550 TI - Diagnosis and management of familial dyslipoproteinemia in children and adolescents. AB - CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2259552 TI - Bronchial reactivity and sex hormone: study in a Turner's population. AB - Respiratory function and bronchial reactivity was studied by carbachol challenge in 41 patients with Turner's syndrome and in 46 controls. In patients and controls the personal and family history of atopic illnesses was evaluated; reactivity to skin allergen tests was studied in patients only. Patients with Turner's syndrome had less allergy skin test reactivity; no difference was found in allergic symptoms between patients and controls despite the patients having a more positive family history of atopy (P less than 0.05). Respiratory function variables were higher in patients than in controls, and bronchial reactivity as expressed by the results of carbachol testing was higher in Turner's patients than in controls (P less than 0.01). Bronchial reactivity was significantly reduced after 6 months of estrogenic therapy (P less than 0.05) in subjects with Turner's syndrome, while the same did not occur in patients who did not receive estrogen treatment. This study of pulmonary function and bronchial reactivity in Turner's patients may help understand the effects of sex hormones in the regulation of bronchial tone and of bronchial response to constrictive agents. PMID- 2259553 TI - Should TGV be measured from end-inspiratory occlusions rather than end-expiratory occlusions in wheezy infants? AB - It has been suggested that thoracic gas volume (TGV) measured in infants in a plethysmograph most accurately represents true lung volume when calculated from end-inspiratory airway occlusions. The rationale proposed is that pressure measured at the mouth underestimates alveolar pressure more at end-expiration than at end-inspiration, presumably due to small airway closure, and this results in greater overestimation of TGV. To investigate this possibility we calculated TGV in 40 wheezy infants from occlusions at both end-inspiration (TGVei) and end expiration (TGVee) using a 60 L whole body plethysmograph. TGV was corrected for equipment dead space and tidal volume. When a significant change in TGV was defined as lying outside the 95% confidence interval of the TGVee measurements, 8 of the 40 infants tested had significantly higher TGV values measured from occlusions made at end-expiration, while two infants had significantly lower TGV values measured from occlusions made at end-expiration. This trend was not more common in infants with "concave" flow-volume curves. Although it is technically easier to make occlusions at end-expiration, occluding at end-inspiration may minimize errors of TGV measures in a few individuals due to small airway closure at low lung volumes. PMID- 2259554 TI - Effect of forced expiration on thoracic gas volume in wheezy infants. AB - Partial expiratory flow-volume curves are commonly used in infant pulmonary function testing. The flow measurements are volume dependent and thoracic gas volume (TGV) is often measured in conjunction with forced expiratory maneuvers. Since it is not possible to make continuous, simultaneous measurements of TGV during forced expiration, it is assumed that lung volume returns to its original value after forced expiration. To test this assumption we measured TGV using a whole body plethysmograph in 14 wheezy infants before and after a series of forced expirations produced with an inflatable jacket. Forced expiration did not cause a significant change in group mean TGV measurements. Examination of individual data did not show any systematic difference between TGV measured before and after forced expiration. These results suggest that repeated forced expirations do not alter TGV within the time scale of usual pulmonary function testing protocols. PMID- 2259555 TI - Varying tracheal cross-sectional area during respiration in infants and children with suspected upper airway obstruction by computed cinetomography scanning. AB - An ultrafast cinetomography computed tomographic scanner (cine-CT) was used to evaluate infants and children (n = 15) with suspected obstruction of the larynx or trachea. One scan sequence provided a single image at each of eight cross sectional levels (volume-mode study). Each study, lasting 224 ms, covered the distance between the supraglottic area and the carina. Each patient also underwent a "dynamic" study at a specific level of interest determined from the volume-mode study. Forty images within 2.3 s covered at least one respiratory cycle. The images were displayed as a closed-loop movie and dynamic changes in laryngeal and tracheal caliber with respiration were monitored and quantitated. Tracheal boundaries were outlined either by a trackball-guided cursor (freehand) or semi-automated computer edge detection, and cross-sectional areas and diameters were determined. Reproducibility was tested among three investigators' freehand drawings and two automated computer drawings, at the same and at varying image intensities. The coefficient of variation for the computer-assisted records (0.2%) was smaller than for the best freehand drawing (1.5%). Tracheal diameters were reproducible, but with greater intra-individual investigator variability. Four normal tracheas had close to published measurements with conventional CT scanners. Cine-CT gives objective tracheal dimensions and their variation during respiration; it provides good anatomical detail above the carina, and also of the extra- and intra-thoracic vessels if injected with contrast medium. PMID- 2259556 TI - Measurements of pulmonary mechanics prior to the elective extubation of neonates. AB - We measured total respiratory system compliance (CRS) and resistance (RRS) by the passive expiratory flow technique prior to the elective extubation of 61 neonates with a history of respiratory distress syndrome. Successful trials of extubation were characterized by a higher mean value of CRS when compared to trials that led to reintubation (1.52 vs. 1.10 mL/cm H2O, P = 0.004). Low values of CRS (0.9 mL/cm H2O or less) were invariably associated with extubation failure, whereas high values of CRS (1.3 mL/cm H2O or greater) were associated with extubation success in 94% of patients. A higher mean value of RRS was recorded in the group of infants who failed extubation when compared to those who were successful (0.22 vs. 0.17 cm H2O/mL/s, P = 0.042). We propose that measurements of pulmonary mechanics, particularly CRS, may be useful in identifying infants who will be at risk for extubation failure. PMID- 2259557 TI - Pulmonary function following positive pressure ventilation initiated immediately after birth in infants with respiratory distress syndrome. AB - Cardiopulmonary function following positive pressure ventilation, initiated immediately after birth, was evaluated in 10 very low birthweight infants with respiratory distress syndrome (RDS; RDS infants). Multiple gas rebreathing methodology was used to measure functional residual capacity (FRC), diffusing capacity of the lung for carbon monoxide (DLCO) and effective pulmonary capillary blood flow (Qeff) at 2, 24, and 72 hr of age. Cardiopulmonary function variables were also measured at 2 hr of age in 10 infants of similar birthweight who did not have RDS (non-RDS infants). In RDS infants, mean FRC at both 2 hr of age (15 mL/kg or 0.42 mL/cm) and 24 hours of age (20 mL/kg or 0.54 mL/cm) was less than published predicted values for healthy infants and significantly less than values in non-RDS infants at 2 hours of age (29 mL/kg or 0.8 mL/cm). By 72 hr of age, mean FRC in RDS infants rose to predicted. At 2 and 24 hours of age, mean Qeff in RDS infants (41 and 38 mL/min/kg, respectively) was below predicted, as well as below the value observed in non-RDS infants at 2 hr of age (62 mL/min/kg). in RDS infants. DLCO remained well below published predicted values throughout the first three days of life. We conclude that early aggressive respiratory therapy does not result in the establishment of normal lung volumes during the first day of life, but it does so by 3 days of age. However, in spite of intubation immediately after birth and the application of continuous positive pressure ventilation during the first 3 days of life, very low birthweight infants with RDS continue to have significant alteration in lung function, evidenced by impaired diffusing capacity of the lung and low arterial-alveolar oxygen tension ratios. PMID- 2259558 TI - Pneumocystis carinii pneumonia in young children with AIDS. AB - We present our experience with 54 episodes of Pneumocystis carinii pneumonia in 50 young children with AIDS, all but one representing congenitally acquired infection. Findings at history and physical examination are not helpful in suggesting the diagnosis. The diagnosis is suggested by marked hypoxemia, diffuse disease on chest radiograph, and elevated serum LDH level. Because important aspects of the history may be withheld, a high index of suspicion may be necessary for the correct diagnosis. The mortality rate for ventilated patients was 50%. PMID- 2259559 TI - [The role of glycolytic enzymes in the etiology and course of bronchopulmonary diseases and drug hypersensitivity in children]. PMID- 2259560 TI - [Diagnostic significance of protein levels in the bronchoalveolar lavage fluid in children with chronic pneumonia]. PMID- 2259561 TI - [Clinical significance of functional and structural changes in cell membranes of children with chronic hepatitis]. PMID- 2259562 TI - [Treatment of acute respiratory diseases in young children]. PMID- 2259563 TI - [Experience with using plasmapheresis in exo- and endogenous poisoning in children]. PMID- 2259564 TI - [Analysis of the indicators of central and peripheral hemodynamics in families with arterial hypertension]. AB - Arterial pressure was studied by ++tacho-oscillography, and the central and peripheral hemodynamics were examined by tetrapolar rheography in members of 62 families with essential arterial hypertension. A geneticodispersion analysis was made of phenotypic dispersion of the parameters under study. The genetic determinant with an X-chromosome effect was established for minimal and lateral systolic pressure; that with a maternal effect for mean pressure. A high degree of the inheritance of the varieties of the central hemodynamics was discovered. Analysis of the peripheral hemodynamics points to an important role played by venoconstriction in the establishment of arterial hypertension. A high level of genetic determination with an X-chromosome effect was found for the readings of the leg rheogram (beta, alpha + alpha, alpha + beta/RR), responsible for the blood content and venous outflow. The data obtained provide evidence in favour of the prospective + search for genetic markers among the parameters of arterial pressure, the central and peripheral hemodynamics. PMID- 2259565 TI - [Parameters of uric acid metabolism in healthy children and in patients with arterial hypertension]. AB - The incidence of hyperuricaemia was examined in 47 adolescents with "border-line" arterial hypertension and in 59 children of the same age with "moderate" arterial hypertension. The control group was made up of 94 healthy adolescents. In healthy children, hyperuricaemia was documented in 9.5% of cases, in patients with "border-line" arterial hypertension in 48.9%, and in those with "moderate" arterial hypertension in 72.9% of cases. The data obtained point to a high degree of hyperuricaemia conjugation with elevation of arterial pressure. Since hyperuricaemia is detectable in part of cases from the birth (the type of constitution), its presence in concrete subjects can be regarded as an early "indicator" of arterial hypertension. PMID- 2259566 TI - [Pathogenesis of various types of tachycardia in childhood]. AB - As many as 33 children with different patterns of tachyarrhythmia were subjected to transesophageal pacing of the left atrium. Thi incidence of the orthodromal pattern of reciprocal AV-tachycardia was the highest (10 patients); antidromal reciprocal AV-tachycardia was only noted in 1 patient. Four patients turned out to have latent Kent's bundle which provoked the development of tachycardia attacks. The slow-fast pattern was revealed in both cases of nodal tachycardia. Among atrial tachycardias, monofocal automatic one was encountered most frequently (9 patients) and only one patient was diagnosed to suffer from reciprocal atrial tachycardia. The determination of the pathogenesis of tachycardia in children with the WPW syndrome is of importance for solving the problem of the successive medicamentous and non-pharmacological treatment character. PMID- 2259567 TI - [Cardiac rhythm in children with emotional stress]. AB - The cardiointervalogram was recorded in 97 children during their stay at the surgical hospital for inguinal or umbilical hernia. The investigation was carried out on day 1 of the child's hospitalization, on the day of operation (30 minutes before premedication) and on the eve of the discharge from the hospital. It has been shown that the negative emotions occurring in the child during stay at the hospital produce considerable changes in the mechanism by which the cardiac rhythm is regulated, interfering with vegetative balance and thus prompting the sympathetic part of the vegetative nervous system to exert a greater influence on the child's body. The tension of the regulatory mechanisms in emotional and stressogenic situations rises with the child's age. The age-associated differences have been revealed in the children's sensitivity to emotiogenic stressful factors of varying nature. PMID- 2259568 TI - [Arrhythmia in children with dilated cardiomyopathy (data of 24-hour ECG monitoring)]. AB - The authors demonstrate potentialities of long-term ECG monitoring in the diagnosis of heart rhythm and conduction disturbances in children with dilated cardiomyopathy. Provide the results of comparative studies of routine and 24-hour ECG monitoring in children with dilated cardiomyopathy under every-day life conditions. Show that during 24-hour ECG monitoring, all the children with the above pathology manifest heart rhythm and conduction disturbances of varying intensity and prognostic significance. PMID- 2259570 TI - [Microcirculation in children operated on for congenital heart defects with arteriovenous shunt]. AB - The author summarizes the data pertaining to the transformation of the structure of the bulbar conjunctiva microcirculatory bed in patients operated on for congenital heart disease with blood shunt from the greater to the pulmonary circulation. It is concluded that the degree of the recovery of the structure and function of the systemic microcirculation ++ depends on the children's age at which they undergo surgical treatment. Evidence is given for the conclusion about the necessity of providing correcting surgery for such patients when they are still in their early age. PMID- 2259569 TI - [Status of the liver in children with cardiomyopathies (data from echographic study)]. AB - In order to estimate the liver status and hemodynamics in children with non rheumatic cardiomyopathies, 130 schoolchildren were examined. Of these, 60 children were diagnosed to have hypertrophic and 70 dilated cardiomyopathy. In both cardiomyopathy varieties, alterations in the liver were established to be of secondary character and associated with greater circulation abnormalities. The patients manifested an appreciable increase of the diameter of the hepatic veins and reduction in them of the blood flow rate. Adequate cardiotropic therapy brought about a noticeable decrease in the echographic signs of liver congestion. PMID- 2259571 TI - [Functional activity of segmentonuclear neutrophils and monocytes in children with different cytologic variants of acute myeloid leukemia]. AB - Bone marrow and blood neutrophils and monocytes were examined over time in 31 patients with different versions of acute myeloid leukemia according to the phagocytosis and NBT tests. As compared to the phagocytic indicators in healthy children, the absorptive activity in the acute disease period was increased and the digestive activity was lowered. Approximation of the digestive activity of blood neutrophils to the control data was only noted in long remissions (over 1 year). Function of mature cells together with other markers can be used as an initial sign of a favourable prognosis of the underlying disease. PMID- 2259573 TI - [Present tendencies in the manifestations of vascular pathology in childhood]. PMID- 2259572 TI - [The role of the mononuclear phagocyte system in the pathogenesis of excessive peritoneal adhesions in children with peritonitis]. AB - A study was made of the significance of mononuclear phagocytes in the outcome of post-inflammatory++ peritoneal repair and onset of peritoneal adhesions. It has been revealed that patients with adhesions occurring in the postoperative period manifest insufficiency of the macrophagal response characterized by a decrease of the content of macrophagal elements in peritoneal exudate and derangement of macrophagal migration in the skin fenestra test during reproduction of aseptic inflammation. It is assumed that stimulation of mononuclear phagocytes can serve a means for preventing peritoneal adhesions. PMID- 2259574 TI - [Relation between disorders of systemic microcirculation and chemotactic activity of macrophages in children with appendicular peritonitis]. AB - As many as 58 children aged 3 to 14 years operated on for destructive forms of appendicitis complicated by diffuse peritonitis were examined for microcirculation of eye conjunctiva microvessels using biomicroscopy and for chemotactic++ activity of macrophages in an area of aseptic inflammatory reaction. The correlation analysis made it possible to reveal specific dependence of macrophagal chemotaxis on primary derangement in one or another component of the microcirculatory bed, the extent of diminution of the arteriolar, capillary and venular lumen as well as on the impairment of blood aggregation in microvessels. Detoxication therapy contributed to the improvement of microcirculation and the growth of the release of macrophages to the area of aseptic inflammatory reaction. PMID- 2259575 TI - [Functional-metabolic activity of the mononuclear phagocyte system of the blood, liver, spleen and skin in children with hepatitis B]. AB - A total of 102 children aged 5 to 14 years with virus hepatitis B were examined for the status of the mononuclear phagocytic system in accordance with the absolute monocyte count in the circulating blood, esterase and acid phosphatase activity in the monocytes, for function of organ macrophages of the liver and spleen using dynamic scintigraphy with TC-colloid and for macrophages of the skin by the "skin window" method. The rise of the absolute count and lowering of the functional and metabolic activity of blood monocytes were directly proportional to the gravity of virus hepatitis B. The changes persisted for a long time, namely up to 1.5 to 3 months since the disease onset. There was a progressive drop of the functional activity of Kupffer cells in the liver with a maximum decrease seen within 4 to 6 weeks since the disease onset, followed by returning to normal in cyclic disease and preservation of the changes in lingering and chronic virus hepatitis B. Spleen macrophages play an active compensatory role, maintaining normal "purifying" function of the mononuclear phagocytic system. That compensatory response tension appeared high in lingering and especially in chronic virus hepatitis and may serve as a criterion for process chronicity. The changes in the mononuclear phagocytic system observed in cyclic course of mild and medium-gravity virus hepatitis B may be regarded as normal adaptive reaction and do not require any drug correction. The latter one may only be indicated in patients with grave, lingering or chronic disease patterns associated with break down or depletion of the adaptive mechanisms of the system in question. PMID- 2259576 TI - [Diagnostic possibilities of tetrapolar thoracic rheography during bicycle ergometry test in children]. AB - The diagnostic potentialities of tetrapolar chest rheography were examined in children with heart pathology, undergoing bicycle ergometry tests of different power. The method applied to 25 patients with organic heart lesions enabled latent heart failure to be diagnosed in 8 of them. The method can be used for the estimation of the treatment and rehabilitation measures with special reference to the follow-up of 119 children suffering from myocardiodystrophy. PMID- 2259577 TI - [Functional state of the cardiorespiratory system in healthy children at rest and during the bicycle ergometry test]. AB - Altogether 25 healthy untrained children aged 9 to 12 years were examined. There were 11 boys and 14 girls. The following parameters were measured at rest and during bicycle ergometry: the heart rate, oxygen consumption, pulmonary ventilation, metabolic units, the ratio of oxygen consumption increment, oxygen pulse, stroke and cardiac indices, index of the Q-Z interval and work fitness. The ECG was recorded as well. During exercise, adequate reaction of the cardiorespiratory system was characterized by linear growth of the heart rate, cardiac index and oxygen consumption together with a proportional shortening of the Q-Z interval. At all levels of exercise the girls manifested more pronounced chronotropic stimulation, leading to the attainment of the submaximal heart rate (1.5 Watt/kg). On chronotropic delay overtension of inotropic function was demonstrable in children exposed to high loads, which was accompanied by restriction of the cardiac index growth. PMID- 2259578 TI - [Differential diagnosis of Campylobacter infections in children]. PMID- 2259579 TI - [Clinical picture of HIV infection in children]. PMID- 2259580 TI - [Human immunoglobulin for intravenous administration in the treatment of infectious and inflammatory diseases in children]. PMID- 2259581 TI - [Health status of schoolchildren and the tasks of its improvement]. PMID- 2259582 TI - [The role of genetic and environmental factors in serum lipid changes in children with various levels of arterial blood pressure (a family study)]. AB - Blood lipid and lipoprotein concentrations were measured in proband children with different levels of arterial pressure and in their relatives in the populational familial study. Based on intrafamilial correlations the component analysis of the phenotypic dispersion of total cholesterol, high density lipoprotein cholesterol and triglyceride concentrations was performed. Qualitative and quantitative differences were shown to exist in genetic and environmental determinants of lipids and lipoproteins in the families of probands with low, high and normal levels of arterial pressure. PMID- 2259583 TI - [The unwanted child]. PMID- 2259584 TI - [Chronic congenital monocytic leukemia in a newborn infant]. PMID- 2259585 TI - [Noonan syndrome]. PMID- 2259586 TI - [Engelmann's disease in a 3-year-old child]. PMID- 2259587 TI - [Bronchoalveolar lavage in children]. PMID- 2259588 TI - [Myocardial hypoxia in newborn infants]. PMID- 2259589 TI - [The role of Campylobacter pylori in lesions of the upper segments of the digestive tract in children]. PMID- 2259590 TI - [Clinico-echographic parallels in autonomic-visceral dysfunctions in infants with perinatal encephalopathies]. PMID- 2259591 TI - [The clinical and pathogenetic aspects of the bronchial obstruction syndrome in young children]. PMID- 2259593 TI - [The effect of Opisthorchis invasion on the clinical picture and immune response of children with viral hepatitis]. PMID- 2259592 TI - [The antioxidant protection of the body in chronic gastroduodenitis and duodenal peptic ulcer in children]. PMID- 2259594 TI - [The growth of children and thyroid function in differentiation disorders of renal tissue]. AB - The growth of children and thyroid function were examined in abnormal differentiation of renal tissue. Forty-four children with different varieties of renal dysembryogenesis were examined. Seventy-three children with acquired renal pathology made up a reference group. Children with congenital nephropathies manifested a higher incidence of delayed growth. The majority of patients with renal dysembryogenesis showed the laboratory signs of both primary and secondary hypothyrosis. The role of thyroid hormones in the genesis of delayed growth and development of children afflicted with renal diseases is under discussion. PMID- 2259595 TI - [The catamnesis of patients with the minimal change nephrotic syndrome--lipoid nephrosis]. AB - A catamnestic study was made of 188 patients suffering from the nephrotic syndrome with minimum changes (NSMC) in order to examine the characteristic features of its course and outcome. The patients' age ranged from 3 to 26 years, with the disease standing being from 1 to 22 years. The authors explored the anamnestic and clinico-laboratory data together with the morphological findings (in 6.9% of cases). Estimated the results of the treatment. Described the NSMC outcome in 188 children. PMID- 2259597 TI - [Renal prostaglandins in glomerulonephritis in children]. AB - Prostanoid excretion with urine in children suffering from glomerulonephritis indicates that in the kidneys the output of prostacycline decreases and that of thromboxan rises. In glomerulonephritis children prostacycline and prostaglandin E promote the maintenance of glomerular filtration, which is evidenced by the reduction of their output in the stage of chronic renal failure. The growth of renin and antidiuretic hormone synthesis in children suffering from nephrotic glomerulonephritis is not accompanied by the increase of the output of prostaglandin E, their renal antagonist, and may be one of the reasons of the development of the edematous syndrome. PMID- 2259596 TI - [The function of the hypophyseal-gonadal system in different variants of glomerulonephritis in children]. AB - A total of 28 children with different varieties of glomerulonephritis were examined for the pituitary-gonadal system (PGS). The examination included measurements of follicle-stimulating and luteinizing hormones, prolactin, estradiol, progesterone and testosterone. To define standards of the content of the hormones under study, 45 children of the control group were examined. The relationship was analyzed between the content of hormones and the disease activity and gravity. The most active phase of glomerulonephritis was characterized by maximal alterations in the content of pituitary and gonadal hormones. The content of the latter ones appeared to be considerably changed in patients with the mixed pattern of glomerulonephritis, attesting to profound functional derangements in the PGS. The intensity of those derangements was determined by the severity of the pathological process. PMID- 2259598 TI - [The immunological indices in chronic glomerulonephritis with a varying clinical course]. AB - Examination of children with chronic glomerulonephritis by means of using immunological indicators of the first level enabled a direct correlation (r = 60) to be established between the relative count of venous blood lymphocytes (the mean values of several studies) and the disease gravity. A regression equation is depicted, making it possible to identify a group at risk for a possible grave course of disease among patients with chronic glomerulonephritis. The relative count of T lymphocytes is the least dynamic and informative indicator for disease forecasting. PMID- 2259599 TI - [The indices of gastric and pancreatic functions in the different clinical syndromes of acute glomerulonephritis in children]. AB - It has been demonstrated that children with different clinical syndromes of acute glomerulonephritis manifest inconclusive changes in enzyme secretory functions of the stomach and pancreas together with the signs of functional insufficiency of the incretory apparatus of the latter one. There is no doubt that the impairment of the activity of the main alimentary glands in children suffering from acute glomerulonephritis aggravates the disease, which should be taken into account in elaborating the multimodality treatment measures for such patients. PMID- 2259600 TI - [The quantitative analysis of the x-ray changes in the kidney calices in chronic pyelonephritis in children]. AB - As many as 89 patients aged 6 months to 14 years with microbial inflammatory diseases of the urinary tract and 40 controls of the same age were examined. Of the patients, 55 had chronic pyelonephritis, 21 acute pyelonephritis, and 13 an infection of the urinary tract. For examination use was made of the planimetric method of measuring the width of the fornix and the cervix of the renal calyces on excretory urography. The fornicocervical index, product of the indicated parameters of the calyces, was computed. In health, that index did not exceed 24 units. In the majority of patients suffering from chronic pyelonephritis, it turned out higher. The false negative results were obtained in 7 cases. The fornicocervical index remained unchanged in patients with acute pyelonephritis and urinary tract infection. It is suggested that the fornicocervical index be computed for use as an objective criterion in the diagnosis of chronic pyelonephritis in children. PMID- 2259601 TI - [The echographic diagnosis of developmental defects of the brain in newborn and nursing infants]. AB - The clinical diagnosis of a lot of developmental abnormalities of the brain presents considerable difficulties and sometimes it is not feasible. The author provides the data obtained during echographic examinations in 52 children with different developmental abnormalities of the brain. Describes an ultrasonic appearance of different varieties of Arnold-Chiari and Dandy-Walker syndromes, agenesia of the corpus callosum, holoprosencephaly, micropolygyria, porencephaly, hydrocephalus, and so forth. Shows the high information content and value of transfonticular echography in the diagnosis of brain abnormalities in children and neonates. PMID- 2259602 TI - [The current problems of intestinal infections in children in the USSR]. PMID- 2259603 TI - [The echocardiographic assessment of heart activity in paroxysmal tachycardia in children]. AB - The echocardiograms of 42 children were examined during paroxysmal tachycardia attacks, as well as 15 minutes and 5 days after them. During paroxysms the electrical and mechanical cardiac activity gets dissociated, the end diastolic volume, the stroke index and ejection fraction decrease which is determined by the reduction of the volume load of the left ventricle because of the shortening of the diastolic phase of the cardiac cycle and the lack of the effective systole of the atria. The late diastolic opening of the mitral valve could not be recorded on the echocardiogram. During the interictal period, the most significant disorders of the cardiodynamics and alterations in the anatomical parameters were discovered in senior children suffering from paroxysmal tachycardia for 3 to 5 years and more. PMID- 2259604 TI - [Imported tropical malaria in children]. PMID- 2259605 TI - [The treatment of severe forms of pertussis in infants in the first months of life]. PMID- 2259606 TI - [The pathogenetic bases of the medical procedure for promoting the health of frequently ill children attending preschool institutions]. PMID- 2259607 TI - [The prevention of postvaccinal complications in children with allergic diseases after ADT-M anatoxin administration]. PMID- 2259608 TI - [The medical and organizational aspects of the problem of the sex education of adolescents]. PMID- 2259609 TI - [An analysis of the extrahospital morbidity of children in Moscow]. PMID- 2259610 TI - [An analytical review of the research in pediatrics completed in 1989]. PMID- 2259611 TI - [The systemic disorder of connective tissue metabolism and hypoplasia of the nephron elements in hereditary nephritis in children]. AB - Clinical biochemistry and morphological methods were employed to examine 25 children aged 3 to 15 years with hereditary nephritis. Measurements were made of morphological alterations in renal biopsy specimens, excretion with urine of connective tissue metabolites (hydroxyproline, hydroxylysine glycosides, glycosaminoglycans), the level of the same metabolites and characteristic features of the cellular growth of skin fibroblasts in culture. The early stages of nephritis development were marked by hypoplasia of nephron elements, followed by dystrophy and destruction of its ultrastructural elements including collagen of the glomerular basal membranes. The status of the skin fibroblast cell culture corresponded with the changes seen in renal cells of mesenchymal origin. The conclusion is made that in children with hereditary nephritis, nephron cells and skin fibroblasts reflect systemic metabolic defect of the connective tissue. PMID- 2259612 TI - [Games psychotherapy and psychoprophylaxis in pediatrics]. PMID- 2259613 TI - [The infusion therapy of acute pneumonia patients]. PMID- 2259614 TI - [Hereditary thrombocytopathy due to a thromboxane A2 deficiency in a newborn infant]. PMID- 2259616 TI - [The role of the pediatrician in the early detection of scoliosis in children]. PMID- 2259615 TI - [Cancer of the adrenal cortex in a 10-year-old girl]. PMID- 2259617 TI - [The counterindications for vaccination]. PMID- 2259618 TI - Abstracts of papers. Clinical Pharmacology meeting. Utrecht (The Netherlands), 5 October 1990. PMID- 2259619 TI - Fingerprinting genomes using PCR with arbitrary primers. AB - Simple and reproducible fingerprints of complex genomes can be generated using single arbitrarily chosen primers and the polymerase chain reaction (PCR). No prior sequence information is required. The method, arbitrarily primed PCR (AP PCR), involves two cycles of low stringency amplification followed by PCR at higher stringency. We show that strains can be distinguished by comparing polymorphisms in genomic fingerprints. The generality of the method is demonstrated by application to twenty four strains from five species of Staphylococcus, eleven strains of Streptococcus pyogenes and three varieties of Oryza sativa (rice). PMID- 2259621 TI - Mutations that alter the ability of the Escherichia coli cyclic AMP receptor protein to activate transcription. AB - The effects of a number of mutations in the E. coli cyclic AMP receptor protein (CRP) have been determined by monitoring the in vivo expression and in vitro open complex formation at two semi-synthetic promoters that are totally CRP-dependent. At one promoter the CRP-binding site is centered around 41.5 base pairs upstream from the transcription start whilst at the other promoter it is 61.5 base pairs upstream. The CRP mutation E171K reduces expression from both promoters whilst H159L renders CRP totally inactive: neither mutation stops CRP binding at either promoter. The mutations K52N and K52Q reverse the effect of H159L and 'reeducate' CRP to activate transcription. CRP carrying both H159L and K52N activates transcription from the promoter with the CRP site at -41.5 better than wild type CRP. In sharp contrast, this doubly changed CRP is totally inactive with respect to the activation of transcription from the promoter carrying the CRP site at 61.5. Our results suggest that CRP can use different contacts and/or conformations during transcription activation at promoters with different architectures. PMID- 2259620 TI - Extinction of retinol-binding protein gene expression in somatic cell-hybrids: identification of the target sequences. AB - The Retinol-Binding Protein (RBP) is expressed primarily in the liver. The regulatory elements involved in its tissue-specific expression have been identified and mapped to the 5' flanking region of the RBP gene. In this paper heterokaryons and somatic cell-hybrids have been produced and analysed in order to demonstrate that the RBP gene is subject to extinction and to identify the target sequences of this phenomenon. We show here that the gene is extinguished in fusions of hepatoma with a variety of cells of different species and embryonic lineages. The repression is not due to loss of the gene and occurs also when chromosome 10, where the gene is located, is inherited from the expressing parental cell-type. Hybrid clones were transfected with constructs carrying DNA segments of different lengths from the 5' flanking region of the RBP gene fused to a reporter gene. We demonstrate that extinction takes place also on an exogenous RBP-CAT gene, mimicking the phenomenon observed with the endogenous gene in its chromosomal location. Moreover, we identify and map the target sequences of the putative extinguishing function. Our data thus show that extinction of RBP is mediated through the DNA segment that is involved in its tissue-specific expression. PMID- 2259623 TI - Synthesis and characterization of a substrate for T4 endonuclease V containing a phosphorodithioate linkage at the thymine dimer site. AB - A dodecadeoxyribonucleotide containing a cis-syn thymine dimer with a phosphorodithioate linkage was synthesized on a solid support using a dinucleotide coupling unit prepared by UV-irradiation of dithymidine monophosphorodithioate followed by S- and 5'-O-protection and 3'-phosphitylation. A photodimer-containing dodecamer without phosphate modification was also synthesized. The dodecamers were hybridized to the complementary sequence, and the duplexes used as substrates for T4 endonuclease V. This enzyme cleaved the phosphate-modified substrate more slowly than the unmodified duplex with the same dissociation constant. PMID- 2259622 TI - Human major histocompatibility complex contains a new cluster of genes between the HLA-D and complement C4 loci. AB - A new cluster of genes has been defined in the human Major Histocompatibility Complex class III region. The seven novel genes, G12 to G18, are localised in a 160 kb segment of DNA extending from the complement gene cluster towards HLA-DR. The genes were identified by isolation of cDNA clones using cosmid genomic inserts as hybridisation probes, and by the detection of the corresponding transcripts in Northern blot analysis. Characterisation of the cosmid genomic DNA inserts, in conjunction with pulsed field gel electrophoresis analysis of uncloned DNA, for the presence of clustered sites for infrequently cutting restriction endonucleases has revealed that at least 5 of the 7 genes are associated with HTF-islands. These unmethylated CpG-rich sequences are frequently found at the 5' ends of ubiquitously expressed genes. Together with previously published data 36 genes have now been defined in a 680kb stretch of DNA within the MHC. With one gene approximately every 20kb of DNA this represents the most densely packed region of the human genome so far characterised, and is of major significance in relation to the mapping and sequence analysis of the rest of the genome. PMID- 2259624 TI - An analytical study of the dimerization of in vitro generated RNA of Moloney murine leukemia virus MoMuLV. AB - The genome of Moloney murine leukemia virus(MoMuLV) is composed of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Recently it was shown that in vitro generated MuLV RNA formed dimeric molecules and that dimerization sequences are located within the Psi encapsidation domain between positions 215 and 420. Conditions for the spontaneous dimerization of a MuLV RNA fragment encompassing the Psi domain have been investigated. The rate of spontaneous MuLV RNA dimer formation is dependent upon RNA, NaCl and MgCl2 concentrations as well as temperature. Thermal denaturation of in vitro generated dimer RNA of 350 nt, from positions 215 to 565, gave a Tm of about 58 degrees C in 100 mM NaCl. This Tm value is very close to that found for RNA corresponding to the 5' 755 nt and to the genomic 70 S RNA isolated from virions. According to thrermodynamic parameters derived from denaturation curves of MuLV dimer RNA generated in vitro, the dimer linkage structure probably involves short sequences. PMID- 2259625 TI - A gene from the VSG expression site of Trypanosoma brucei encodes a protein with both leucine-rich repeats and a putative zinc finger. AB - The transcription unit of the gene for the variant specific glycoprotein (VSG) AnTat 1.3A of Trypanosoma brucei contains several associated genes (ESAGs, for Expression Site-Associated Genes), 7 of which have already been described. We report here the characterization of a further ESAG, which we term ESAG 8, present 1 kb downstream from the putative adenylate cyclase gene ESAG 4. ESAG 8 encodes a 70 kd protein whose sequence indicates that it is probably not exposed at the cell surface. With the exception of the N-terminal domain which contains a presumptive DNA-binding zinc finger, the ESAG 8 protein consists exclusively of leucine-rich repeats of 23 amino acids, typical of protein-interacting domains such as the RAS-interacting region of the yeast adenylate cyclase. ESAG 8 transcripts are only found in bloodstream forms, and their level is particularly low, suggesting a high rate of degradation. The ESAG 8 protein may be involved in stage-specific regulatory processes, such as gene expression control or adenylate cyclase activation. PMID- 2259626 TI - U4B snRNA gene enhancer activity requires functional octamer and SPH motifs. AB - Expression of the chicken U4B small nuclear RNA (snRNA) gene is stimulated by a transcriptional enhancer located approximately 190-227 base pairs upstream of the transcription start site. This enhancer is composed of at least two functional motifs: an octamer (binding site for Oct-1) and an SPH motif. We now report that these two motifs functionally cooperate to stimulate U4B snRNA gene expression, and both are required for the formation of a stable transcription complex. Expression in frog oocytes of 24 different point mutant constructions indicates that the functional SPH motif is at least 15 base pairs in length. It is a recognition site for a sequence specific DNA-binding protein, termed SBF, purified from chicken embryonic nuclear extracts. The ability of the mutant SPH motif constructions to be recognized by SBF in vitro correlates with their transcriptional activities, suggesting that SBF mediates the stimulatory effect of the U4B SPH motif. These results are similar to our recent findings on the chicken U1 gene enhancer, which also contains adjacent binding sites for Oct-1 and SBF. These studies, together with evolutionary considerations and sequence comparisons among snRNA gene enhancers, suggest that cooperativity between octamer and SPH motifs could be a widely-employed mechanism for generating vertebrate snRNA gene enhancer activity. PMID- 2259627 TI - Positive and negative transcriptional regulatory elements in the early H4 histone gene of the sea urchin, Strongylocentrotus purpuratus. AB - The early H4 (EH4) histone gene of the sea urchin, Strongylocentrotus purpuratus, is shown to contain at least five positive-responding sequence elements and one negative-responding site which control the level of in vitro transcription in an embryonic nuclear extract. The positive acting elements are: 1) the UHF-1 region, located between -133 and -102 (the site of a strong footprint, due at least in part to the binding of an 85 kD protein factor termed UHF-1); 2) the H4 specific element (H4SE), situated between -62 and -39; 3) a sequence corresponding to a TATA box between -33 and -26 (TAACAATA); 4) the transcriptional initiation site; and 5) an internal sequence element found between +19 and +50. Deletion of, or base changes in, the UHF-1, H4SE, initiation, or internal sequence sites resulted in significant decreases in transcription. Base substitutions in the TATA-like sequence had much less effect, resulting in no more than a 2-fold decrease in transcription, and there was no evidence that alternative initiation sites are utilized in the mutant templates. The negative element (termed the UHF-3 site) is contained within a footprinted region between nucleotides -75 and -56. Base substitutions in this area result in templates that were transcribed at a level 1.2-2.0-fold higher than the wild-type gene. Transcription levels of double UHF 1/H4SE and UHF-1/INR mutants were those expected from additive effects of the individual mutations and there was no suggestion of synergism. PMID- 2259628 TI - Promoter selectivity of Escherichia coli RNA polymerase: effect of base substitutions in the promoter -35 region on promoter strength. AB - A set of 18 variant lac UV5 promoters was constructed, each carrying a single base substitution within the -35 region (nucleotide positions from -36 to -31 relative to the transcription start site). Using truncated DNA fragments carrying these variant promoters and purified Escherichia coli RNA polymerase holoenzyme, in vitro mixed transcription assays were performed to determine two parameters governing promoter strength: i.e., the binding affinity to RNA polymerase (parameter I) and the rate of open complex formation (parameter II). The following conclusions were drawn from the data presented: (1) Alteration in the promoter strength of variant promoters is dependent on both the position and base species of substitutions; (2) the consensus sequence (TTGACA) exhibits the highest values for both parameters; (3) base substitutions at nucleotide position -34 cause marked effect on both parameters; (4) cytosine at nucleotide position 32 can not be replaced with other nucleotides without significant reduction of the promoter strength; and (5) base substitution at nucleotide position -31 exerts only a little effect on parameter I. All these findings were confirmed by abortive initiation assays. PMID- 2259629 TI - Development of novel inhibitor probes of DNA polymerase III based on dGTP analogs of the HPUra type: base, nucleoside and nucleotide derivatives of N2-(3,4 dichlorobenzyl)guanine. AB - 6-(p-Hydroxyphenylhydrazino)uracil (H2-HPUra) is a selective and potent inhibitor of the replication-specific class III DNA polymerase (pol III) of Gr+ bacteria. Although formally a pyrimidine, H2-HPUra derives its inhibitory activity from its specific capacity to mimic the purine nucleotide, dGTP. We describe the successful conversion of the H2-HPUra inhibitor prototype to a bona fide purine, using N2-(benzyl)guanine (BG) as the basis. Structure-activity relationships of BGs carrying a variety of substituents on the aryl ring identified N2-(3,4 dichlorobenzyl)guanine (DCBG) as a nucleus equivalent to H2-HPUra with respect to potency and inhibitor mechanism. DCBdGTP, the 2'-deoxyribonucleoside 5' triphosphate form of DCBG, was synthesized and characterized with respect to its action on wild-type and mutant forms of B. subtilis DNA pol III. DCBdGTP acted on pol III by the characteristic inhibitor mechanism and formally occupied the dNTP binding site with a fit which permitted its polymerization. PMID- 2259630 TI - Loosened nucleosome linker folding in transcriptionally active chromatin of chicken embryo erythrocyte nuclei. AB - We have investigated the mechanism of the electrophoresis-driven chromatin aggregation which had been described by Weintraub (1984, Cell 38, 17-27) as a putative mean for propagation of genetic repression in eukaryotes. We show that the oligonucleosome aggregates are assembled de novo at the starting zone of DNP electrophoresis. A new system of native two-dimensional DNP electrophoresis has been worked out to separate the oligonucleosome aggregates ('A' particles) and the freely-migrating oligonucleosomes ('B' particles). The 'B' particle fraction which is derived from transcriptionally-active chromatin regions undergoes an extensive nuclease degradation of its DNA termini during the nuclease digestion. This fraction is partially depleted of histones H1 and H5 and is enriched in HMG nonhistone proteins. 'A' particles comprise the repressed chromatin DNA fragments which are about 60 b.p. longer than the corresponding DNA oligomers of 'B' particles. An oligonucleosome preparation containing the elongated DNA oligomers has been also isolated by means of sucrose gradient ultracentrifugation. Exonuclease III mapping reveals that the two chromatin fractions differ by an extent of terminal linker DNA trimming during the Micrococcal nuclease digestion rather than by the nucleosome repeat length. The complex character of nuclease digestion is not observed when the chromatin is digested in solution after the nuclear lysis. We argue that the protection of terminal oligonucleosome linkers is due to selective condensation of inactive chromatin in chicken erythrocyte nuclei and that the terminal DNA tails together with linker histones bound to them mediate the aggregation of repressed chromatin fragments. PMID- 2259632 TI - Site-specific mutagenesis using asymmetric polymerase chain reaction and a single mutant primer. AB - A method is described for preparing site-specific mutants using a polymerase chain reaction (PCR) based protocol. The protocol requires a single mutant primer, and has been used to introduce mutations into DNA fragments ranging in size from 200 bp to 1569 bp in length in the GM-CSF, beta-actin, human growth hormone and erythropoietin genes. Sequence analysis of PCR derived mutant fragments shows an error rate of less than one bp change per 1500 bp incorporated. Single base pair mutations have been introduced into these genes which create unique restriction sites. We demonstrate that these mutant templates may be used for competitive PCR to quantitate mRNA and DNA. This method thus offers a rapid means for producing competitive templates for use in quantitative PCR. PMID- 2259633 TI - Nucleotide sequence of a cDNA encoding Wnt-1 of the Mexican axolotl Ambystoma mexicanum. PMID- 2259631 TI - Structure and function of the enhancer 3' to the human A gamma globin gene. AB - An enhancer is located immediately 3' to the A gamma globin gene. We have used DNase I footprinting to map the sites of interaction of nuclear proteins with the DNA sequences of this enhancer. Eight footprints were discovered, distributed over 600 base pairs of DNA. Three of these contain a consensus binding site for the erythroid specific factor GATA-I. Each of these GATA-1 sites had an enhancer activity when inserted into a reporter plasmid and tested in human erythroleukemia cells. Other footprints within the enhancer contained consensus binding sequences for the ubiquitous, positive regulatory proteins AP2 and CBP-1. An Sp1-like recognition sequence was also identified. Synthetic oligonucleotides encompassing two of the footprints generated a slowly migrating complex in gel mobility shift assays. The same complex forms on a fragment of the human gamma globin gene promoter extending from -260 to -200. The DNaseI footprint of this protein complex with the enhancer overlapped a sequence, AGGAGGA, found within the binding site for a protein that interacts with the chicken beta globin promoter and enhancer, termed the stage selector element. We propose that this complex of proteins may be involved in the human gamma globin promoter-enhancer interaction. PMID- 2259634 TI - Nucleotide sequence of a mouse 5S rRNA variant gene. PMID- 2259635 TI - Serendipitous amplification by the polymerase chain reaction (PCR) of two adjacent tRNA(Gln)UUG) genes on target human genomic DNA. PMID- 2259636 TI - Nucleotide sequence of a novel crystal protein gene isolated from Bacillus thuringiensis subspecies kenyae. PMID- 2259637 TI - Nucleotide sequence of chloroplast tRNA(Leu)/UA m7G/from Chlamydomonas reinhardtii. PMID- 2259638 TI - Molecular cloning, nucleotide sequence heterozygosity and regulation of rabbit serum amyloid A cDNA. PMID- 2259639 TI - Nucleotide sequence of cell-to-cell transport protein gene of odontoglossum ringspot virus. PMID- 2259640 TI - Northern analysis of gene-specific primary transcripts using synthetic oligonucleotide probes labeled at high specific activity. PMID- 2259641 TI - A rapid method for determining clone frequency in complex populations using PCR and the Poisson distribution. PMID- 2259642 TI - Low pressure DNA shearing: a method for random DNA sequence analysis. PMID- 2259643 TI - Single step large scale site-directed in vitro mutagenesis using multiple oligonucleotides. PMID- 2259644 TI - DNA fingerprinting with 35S nucleotides. PMID- 2259645 TI - A rapid method for isolating high quality plasmid DNA suitable for DNA sequencing. PMID- 2259646 TI - Formamide can dramatically improve the specificity of PCR. PMID- 2259647 TI - F10, the gene for the glycine-rich major eggshell protein of Schistosoma mansoni recognizes a family of hypervariable minisatellites in the human genome. PMID- 2259648 TI - Dinucleotide repeat polymorphism at the human thrombospondin gene (THBS1). PMID- 2259649 TI - Dinucleotide repeat polymorphism at the int-2 proto-oncogene locus (INT2). PMID- 2259650 TI - Trinucleotide repeat polymorphism at the human pancreatic phospholipase A-2 gene (PLA2). PMID- 2259651 TI - Dinucleotide repeat polymorphism at the D11S490 locus. PMID- 2259652 TI - Dinucleotide repeat polymorphism at the D21S13E locus. PMID- 2259653 TI - CA repeat polymorphism at the ASS locus. PMID- 2259655 TI - [Orthodontic repositioning of an impacted supernumerary tooth]. PMID- 2259654 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2259656 TI - [Changes in the sub-nasal profile of the aging adult]. PMID- 2259657 TI - Ethics in residency. PMID- 2259658 TI - Universal access to health care. PMID- 2259659 TI - Decreased pain with lower flexural rigidity of uncemented femoral prostheses. AB - One hundred one consecutive uncemented hip arthroplasties (87 patients) were analyzed radiographically at 1-year follow up to relate mechanical factors to hip pain as determined by clinical pain scores. The average area moment of inertia and flexural rigidity were greater for the bone than the metal prosthesis for each type of prosthesis (AML, HG, PCA). Normalization of the flexural rigidity ratio (bone to prosthesis) for patient weight yielded a Spearman correlation coefficient of 0.232, significant at P = .02, suggesting that both applied stress and bending stiffness have an effect on pain. No relationship was seen between pain and AP, or average gap between prostheses and bone. PMID- 2259660 TI - Congenital vertical talus: surgical correction by a one-stage medial approach. AB - A single stage procedure for correction of congenital vertical talus using a medial approach is described. The operation was performed on 14 feet with good initial anatomical results in all cases. No wound healing complications were observed. PMID- 2259661 TI - Femoral varus and acetabular osteotomies in cerebral palsy. AB - Sixty-three patients with cerebral palsy underwent proximal femoral varus derotation osteotomy for 86 subluxing or dislocating hips. Eleven hips underwent concomitant pelvic osteotomy. Adductor tenotomy was performed in all patients. The average preoperative femoral neck shaft angle was 158.2 degrees, with a center edge angle of -2 degrees. Femoral osteotomy effected an average femoral neck shaft angle of 132.2 degrees, with a center edge angle of +8 degrees. A Chiari osteotomy was performed when the acetabular index was greater than 35 degrees. This preoperative acetabular index of 46 degrees improved to 28 degrees postoperatively, and proved to be the most reliable indicator for need of an added pelvic osteotomy. PMID- 2259663 TI - Familial osteochondritis dissecans. PMID- 2259662 TI - Ankle fusion: a retrospective review. AB - The results of ankle fusion were reviewed in 26 patients who underwent 32 arthrodesis procedures. Posttraumatic degenerative arthritis was the most common indication for fusion (54%). Crossed cancellous screws were the primary method employed (43%), with an external fixator being used in 22% of cases. The overall union rate was 81%, with both crossed cancellous screws and external fixation attaining the best results (86%). Nonunion and infection were the most frequent complications. Progression of subtalar arthritis was demonstrated in 29% of patients postoperatively. Seventy-eight percent of patients graded extremity appearance as excellent or good, with the majority being able to return to work. PMID- 2259664 TI - Sciatic nerve entrapment in an osseous tunnel as a late complication of fracture dislocation of the hip. PMID- 2259665 TI - Acute traumatic arteriovenous fistula following a gunshot wound to the femur. PMID- 2259666 TI - Hereditary multiple diaphyseal sclerosis: a tumor simulator. PMID- 2259667 TI - Unstable adult midclavicular fracture. PMID- 2259668 TI - Operative management of clubfoot. PMID- 2259669 TI - The role of patient advocacy in health policy. PMID- 2259670 TI - Eosinophilic granuloma. PMID- 2259671 TI - Eosinophilic granuloma of the spine with neurological deficit. AB - A case of a 14-year-old boy with a solitary eosinophilic granuloma of the thoracic spine, with paraplegia secondary to the collapse of the vertebra and peridural spread of tumor, is presented. It is the 14th case recorded in literature to this date. This disease is self-limiting, and there is no role of steroids or radiotherapy observed. PMID- 2259672 TI - Brodie's abscess: a diagnostic dilemma and therapeutic challenge. PMID- 2259673 TI - Pediatric rehabilitation. PMID- 2259675 TI - Issues in the management of children with spastic cerebral palsy. AB - Management of the child with spastic cerebral palsy is multidisciplinary and family-oriented, with emphasis on maintaining and increasing function and preventing deformities. Assessment, family education, and use of multiple forms of therapy in conjunction with assistive technology will result in optimum outcome. The pediatrician must know about and refer children to specialists who are knowledgeable about management of cerebral palsy. Education, vocational training and preparation for independent or assisted living situations are integral parts of management, and the pediatrician must be aware of community resources. PMID- 2259674 TI - Return to school following severe closed head injury: a critical phase in pediatric rehabilitation. AB - Accidents are the major cause of mortality and morbidity in children over the age of 1 in the United States. Significant numbers sustain closed head injuries severe enough to cause permanent disability and dependence. A critical phase in recovery is the return to school. Many necessary ongoing services are provided by public school systems, but children with neurosequelae of severe closed head injury differ from children traditionally served in special education programs. Smooth transition from hospital to school requires informed participants and interagency cooperation. PMID- 2259676 TI - Burns in children and adolescents: initial management as the first step in successful rehabilitation. AB - Burns, the most devastating injuries known, are the second leading cause of nonvehicular accidental deaths. Approximately one-third of these deaths occur in children less than 16 years of age. In this age group, burns are the number one cause of accidental death in the home. Successful rehabilitation begins with skilled initial management. PMID- 2259677 TI - Pediatric spinal cord injury: treatment and outcome. AB - Spinal cord injury results in dramatic disturbances of motor, sensory and autonomic function. Every aspect of a child's life is significantly and usually irreversibly altered. As a condition with low incidence and protean manifestations, the acute care and rehabilitation of spinal cord injured children requires the specialized care, knowledge and experience of a multidisciplinary team found in regional centers. Functional outcome depends on the level and completeness of the spinal cord injury, comprehensive training and education, and the skillful prescription of adaptive technology and aids. Long-term care and management by rehabilitation personnel in concert with the primary care pediatrician will ensure the maintenance of functional independence and general health. PMID- 2259678 TI - Psychosocial consequences of head injury in children and adolescents: implications for rehabilitation. AB - Studies measuring psychosocial outcome in children and adolescents have shown that head injury leads to cognitive impairment which is directly related to the severity of injury in those with very severe head injury. Psychiatric disorders are also related to the severity of injury but here the relationship suggests that mediating factors are involved. No specific pattern of post-traumatic psychological/psychiatric dysfunction emerges from the studies, but it is clear that, as with adults, psychosocial recovery lags behind physical. Head injury affects the functioning of the young person in the family, at school, and within the wider community, often resulting in a secondary handicap of low self-esteem. The multitude of deficits which are a consequence of severe head injury present a challenge for rehabilitation specialists. A multi-disciplinary, multi-specialist, and multi-agency response is required. As a result, families are often presented with a bewildering array of treatments and programmes at different agencies. A case manager can be helpful in ensuring the appropriate use of available resources and can be the one professional in charge of a coordinating case record. PMID- 2259679 TI - Rehabilitation of the injured athlete. AB - An increase in the rate of injuries has accompanied the boom in sports participation among children and adolescents. Accurate diagnosis, prompt treatment, and comprehensive rehabilitation are keys to the safe return of the young athlete to sports. Reacquisition of flexibility, strength, and endurance forms the basis of reconditioning. A graded reacclimatization to the demands of the sport allows the athlete to attain the preinjury level of skill. Psychological ramifications of injury such as fear, anger, and depression are to be expected and must be dealt with appropriately. PMID- 2259680 TI - Pediatric physical therapy in a rehabilitation setting. AB - Pediatric rehabilitation is a rapidly growing field. Managing the pediatric patient requires experience and the appreciation of the contributions of health, social and educational professionals: physician, nurse, occupational therapist, learning specialist, recreational therapist, psychologist, social worker, and physical therapist. The responsibility of this multidisciplinary team is to assist the family and the child in attaining the highest realistic physical independence, to prevent musculoskeletal deformity and, therefore, to improve the overall quality of life. Successful rehabilitation will depend on the degree to which each professional considers the whole child when working to alleviate specific handicaps. The long-term rehabilitation of the pediatric patient is a joint team-family responsibility, and for treatment to be translated into daily life, full cooperation and commitment from the family is crucial. The physician is the coordinator of the rehabilitation team and is responsible for the initial assessment and diagnosis from which the team undertakes appropriate management. Ideally, the physician and team members communicate frequently to ensure congruent goals of treatment. The role of the physical therapist in the management of the pediatric rehabilitation patient relates to classifications of diagnosis. The authors present this guide to families and health professionals for using physical therapy resources. PMID- 2259681 TI - Occupational therapy in pediatric rehabilitation. AB - Occupational therapy in pediatric rehabilitation focuses on the effects of diseases and of the environment on a child's abilities to function successfully in daily life settings (home, school and playground) and roles (family member, student, etc.). In this paper, the process of pediatric occupational therapy, from assessment to discharge planning, is briefly described. Pediatric occupational therapy intervention strategies including treatment, environmental adaptation, and systems change are presented and illustrated. Three case studies highlighting occupational therapy intervention are discussed. PMID- 2259682 TI - The changing role of the speech-language pathologist in pediatric rehabilitation/habilitation. AB - The speech-language pathologist shares in the management of children who have a need for pediatric rehabilitation/habilitation services. Technological advances provide new tools to assess and promote communication. PMID- 2259684 TI - 'Someone must be to blame' syndrome. PMID- 2259685 TI - The child with a headache. PMID- 2259683 TI - Rehabilitation engineering in pediatrics. AB - Applications of science and technology in the (re)habilitation of children and young adults can have dramatic, positive influences on their lives. Prosthetics, orthotics, mobility, postural support and seating, communication and education are responsibilities of the rehabilitation engineer. A holistic approach in meeting individual needs for technology is essential. The concerted rehabilitation engineering programme at The Hugh MacMillan Rehabilitation Centre supports service programmes with relevant research and development work. PMID- 2259686 TI - Fragile-X syndrome. PMID- 2259687 TI - Diagnosis of childhood deafness. PMID- 2259688 TI - Better home care of asthma. PMID- 2259689 TI - The GP consultation. PMID- 2259690 TI - The doctor's health. Under stress? PMID- 2259691 TI - The doctor's health. Violence and safety. PMID- 2259692 TI - Who treats the doctor? PMID- 2259693 TI - Supporting the addicted doctor. PMID- 2259694 TI - The doctor's health. Psychosis and depression. PMID- 2259695 TI - Practice formularies. PMID- 2259696 TI - Prescribing for the diabetic. PMID- 2259697 TI - NRL-3D: a sequence-structure database derived from the protein data bank (PDB) and searchable within the PIR environment. AB - The protein identification resource (PIR) and the Brookhaven National Laboratory protein data bank (PDB) are well-known databases for primary sequences and three dimensional structures of proteins, respectively. Lesk et al, have compared the primary sequences in these two databases and concluded that the sequences in them are not redundant. Moreover, PIR programs can not be used directly on PDB files to access primary sequences because the FORMATS of these two data bases are different. We have developed a sequence-structure database, called NRL-3D, from the sequences, chain identification and the residue numbers of proteins in the PDB. This new database is designed such that it can be used in conjunction with PIR programs to search and extract sequences of interest and the corresponding three-dimensional coordinates from the structures in PDB. PMID- 2259699 TI - Society for Experimental Biology and Medicine. Membership directory. PMID- 2259698 TI - The following protein sequences were reprinted from the protein sequence database of the Protein Identification Resource (PIR). PMID- 2259700 TI - Aging: hypothalamic catecholamines, neuroendocrine-immune interactions, and dietary restriction. AB - The decline in hypothalamic catecholamine (CA) activity with age in rats leads to a reduction in hormone secretion by the neuroendocrine system, and results in decreased reproductive function, a reduction in protein synthesis, development of numerous mammary and pituitary tumors, and probably contributes to the decline in immune function. Some of these same effects can be produced in young rats by administration of drugs that lower hypothalamic CA activity. Administration of drugs to old rats that elevate hypothalamic CA activity can inhibit or reverse the reproductive decline, increase protein synthesis, induce regression of mammary and pituitary tumors, decrease disease incidence, probably elevate immune function, and significantly extend the life span. Therefore, hypothalamic CA have a critical role in the development of aging processes. When young or mature rats or mice are fed a caloric restricted diet, aging processes are inhibited and life span is significantly lengthened. These effects are believed to be mediated primarily via the neuroendocrine system, since calorie restriction results in decreased secretion of hypothalamic, pituitary, and target gland hormones. The decline in hormone secretion leads to a reduction in most body functions, lowers whole body metabolism, and reduces gene expression, and thereby results in a decreased rate of aging of body tissues and longer life. These effects of caloric restriction can be counteracted by administration of hormones, providing evidence that the favorable effects on aging are mediated by reducing hormone secretion. PMID- 2259701 TI - Lipid-derived mediators in insulin action. PMID- 2259702 TI - Growth and development of brain of artificially reared hypoketonemic rat pups. AB - Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply. PMID- 2259703 TI - Age-related inequality between rates of formation and resorption in various whole bones of rats. AB - Variations in rates of bone turnover, consisting of bone formation and bone resorption, were characterized as a function of age and types of bone. Bone formation and bone resorption were quantified and compared in four ages of growing male rats (newborn, 0-2 weeks; weaning, 4-7 weeks; adolescence, 10-14 weeks; and mature, 15-23 weeks) for cephalic bone (calvaria), appendicular bone (femur), axial bones (sixth lumbar vertebrae and sternum), and the pelvis. In all four ages studied, inequality between the rates of bone formation and resorption existed in all bones, and the magnitude of the differences in metabolic imbalance turnover was age and bone type dependent. Formation was consistently higher than resorption in all five bones throughout the entire experimental periods. The ratio of resorption to formation was the lowest at birth (under 0.10:1) for all five bones and then increased. The most rapid bone growth in terms of bone calcium mass occurred at the weaning age (the net gain of calcium per bone per day was the highest) for all bones except the lumbar vertebrae, which occurred at adolescence. The magnitude of the inequality in the rates of bone formation and resorption was greatest in the newborn and diminished with age towards equality. At maturity, the ratio of resorption to formation was under 0.50:1 in the most dense or calcified bones such as the calvarium (0.40:1) and femur (0.49:1), and over 0.50:1 in the relatively thin cortex and well-trabeculated axial bones (0.60:1 in lumbar vertebrae and 0.75:1 in the sternum) and the pelvis (0.91:1). Additionally, large bones (calvaria, long bones, and pelvis) seemed to play an important role in regulating calcium homeostasis starting form the weanling age, since the amount of calcium released from each whole bone per day was high in these bones due to their large mass. PMID- 2259704 TI - Factors affecting cold-induced hypertension in rats. AB - A 3- to 4-week exposure of rats to a cold environment (5 +/- 2 degrees C) induces hypertension, including elevation of systolic, diastolic, and mean blood pressures and cardiac (left ventricular) hypertrophy. The studies described here were designed to investigate some factors affecting both the magnitude and the time course for development of cold-induced hypertension. The objective of the first study was to determine whether there was an ambient temperature at which the cold-induced elevation of blood pressure did not occur. The objective of the second experiment was to determine whether body weight at the time of exposure to cold affected the magnitude and time course for development of hypertension. To assess the first objective, male rats were housed in a chamber whose temperature was maintained at 5 +/- 2 degrees C while others were housed in an identical chamber at 9 +/- 2 degrees C. After 7 days of exposure to cold, the rats exposed to the colder temperature had a significant elevation of blood pressure (140 +/- 2 mm Hg) compared with the group maintained at 9 degrees C (122 +/- 3 mm Hg). The rats exposed to 9 degrees C had no significant elevation of systolic blood pressure at either 27 or 40 days after initiation of exposure to cold. At the latter time, the temperature in the second chamber was reduced to 5 +/- 2 degrees C. By the 25th day of exposure to this ambient temperature, the rats had a significant increase in systolic blood pressure above their levels at 9 degrees C. Thus, there appears to be a threshold ambient temperature for elevation of blood pressure during exposure to cold. That temperature appears to lie somewhere between 5 and 9 degrees C. The second objective was assessed by placing rats varying in weight from approximately 250 to 430 g in air at 5 degrees C. There was a highly significant direct relationship (r = 0.96) between body weight at the time of introduction to cold and the number of days required to increase systolic blood pressure by 10 mm Hg above pre-cold exposure level. The third objective was to make an initial assessment of potential differences among strains of rats with respect to development of cold-induced hypertension. To this end, rats of the Fischer 344 strain were used. Systolic blood pressures of these rats also increased during chronic exposure to cold.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2259705 TI - Prolactin and progesterone receptors in pregnancy-dependent mammary tumors in GR/A mice. AB - In this study, cellular prolactin receptors and cytosolic progesterone receptors were examined and compared in pregnancy-dependent mammary tumors (PDMT) and in normal mammary glands of pregnant GR/A mice. PDMT and normal mammary glands were examined in the same animal, thus assuring an identical hormonal environment. The PDMT cells had a larger capacity to bind prolactin or the synthetic progesterone, R5020, than did the normal mammary gland. While the dissociation constant (Kd) value for prolactin binding to normal mammary epithelial cells was similar to that of PDMT cells, PDMT cells had 2.2 times more prolactin receptors than the normal cells. Progesterone binding activity was detected only in PDMT, but not in the normal mammary cells. The receptor concentration and the Kd value for progesterone binding of PDMT were 606 fmol/mg protein and 3.53 nM, respectively. It appears, therefore, that normal regulation of these receptors may be altered within the PDMT cells. The increased growth responsiveness of PDMT to the hormones of pregnancy, especially prolactin, progesterone, and placental lactogen, may be a function of a sharp increase in the level of cellular receptors for these mammotropic hormones. PMID- 2259706 TI - Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep. AB - In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism. PMID- 2259707 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 2259708 TI - The position of delusional parasitosis in psychiatric nosology and classification. AB - Discussions on the nosological position of delusional parasitosis (DP) have resulted in a wide range of opinions. In the present study in 34 patients with DP, the various and contradictory opinions concerning DP positioning in psychiatric nosology were examined through clinical, psychopathological, and polydiagnostic analyses using VRC, DSM-III, DSM-III-R and ICD-9. The psychopathological analyses with VRC as well as the polydiagnostic comparisons with other classification systems indicated that DP is neither a nosological entity nor due to a specific psychiatric illness. As our results showed, DP is a nosologically unspecific syndrome, which may occur superimposed on all psychiatric disorders. PMID- 2259709 TI - Are there differences in the course of delusional disorders in different periods of time? AB - The results of two follow-up studies on delusional disorders of midlife of probands who fell ill in different periods of time with different access to treatment (modern pharmacotherapy not developed - developed) are compared with each other. The frequencies of uniform versus polymorphous and episodic versus chronic course did not differ in the two studies. These data suggest that the form of course belongs to the natural history of the disorder. The authors stress the importance of developing differentiated prognostic instruments, mainly in order to ameliorate prognostic hypotheses as a basis for rational therapeutic interventions. PMID- 2259710 TI - Peter Berner--on the occasion of his 65th birthday. PMID- 2259711 TI - Prognosis of cardiac phobia. AB - The 36 inpatients who entered this prospective study were admitted to hospital because of cardiac phobia. Their treatment consisted of a behavior therapy program. Twenty-nine of them could be reexamined after 2 1/2 years: 41% were free of symptoms during more than 75% of the follow-up period; 59% suffered recurrences of their anxiety. One patient had committed suicide. A lower educational level, being single, and interpersonal difficulties and conflicts were the sociodemographic factors associated with a poor prognosis; a long pretreatment period of illness and the presence of depression or agoraphobia on admission were significantly more frequently correlated with an unfavorable outcome. The onset sequence of depression, agoraphobia and anxiety attacks was also of prognostic relevance. PMID- 2259712 TI - Obsessive-compulsive disorder: course and interaction with depression. A review of the literature. AB - Long-term follow-up studies suggest that obsessive-compulsive disorder (OCD) is commonly associated with co-morbid conditions such as depression anxieties and phobias. In the review of the literature the weaknesses in the current methodology are discussed. The instruments for measurement of severity are lacking reliability and sensitivity to change. Serious questions are asked about whether the measured changes reflect alterations in depression in general, or obsessional phenomena specifically. No instruments exist for the documentation of long-term course of OCD and documentation of psychotherapy and pharmacotherapy. In a preliminary report we want to introduce our own study. Approximately 40 OCD inpatients of the psychiatric clinic, University of Vienna, with and without primary or secondary depression diagnosed simultaneously by DSM-III-R and ICD-9 criteria will be included in the study. In general, the major goal of the preliminary reported study will be the elaboration of predictors for course, outcome and therapy response. PMID- 2259713 TI - Psychometric assessment of DSM-III personality disorders: another facet of the problem. AB - An empirical study with the Personality Diagnostic Questionnaire, which in substance follows exactly the criteria of personality disorders described in the DSM-III, is used to highlight a number of problems connected with the DSM-III. Criticisms of the DSM-III previously expressed by other authors, e.g. concerning multiple choice between characteristics and equal weighting of different symptoms, are supported by this empirical study. PMID- 2259714 TI - Diagnosis of chronic alcoholism--classificatory problems. AB - Since Magnus Huss introduced the diagnosis of 'chronic alcoholism' into medical literature in 1849, two unsolved problems concerning classification have remained: (1) Differentiation between problem drinkers and chronic alcoholics fluctuates, whereby the cut point of differentiation between abuse and addiction remains differently defined by different authors. Some authors view alcohol induced damage as a building-stone of diagnosis of chronic alcoholism whereas other authors define these damages as illnesses developed as a consequence of chronic alcohol intake. This fact is also mirrored in the different definitions of chronic alcoholism by different classification systems, like ICD-9, DMS-III or DMS-III-R. Valid and reliable questionnaires, like the Munich Alcoholism Test or the Problem Drinking Scale did not succeed in solving this problem of definition, either. (2) The fact that chronic alcoholics are sick--in the sense of a biological-medical approach--is undoubted. Our research group was able to prove that chronic alcoholic patients metabolize methanol in a different way from that of healthy persons. The biological, sociological and psychopathological heterogeneity of this illness has been stressed for more than a century. A prospective long-term study carried out over 4-7 years has led to the development of a new typology in chronic alcoholism that is able to differentiate subgroups of chronic alcoholic patients cross-sectionally in a clinical, biochemical and neurophysiological way. Diagnosis according to this typology qualitatively differentiates patients in many spheres other than drinking behavior. These subgroups also require correspondingly modified therapeutic strategies. PMID- 2259715 TI - A contribution to classification of hallucinations. AB - Proceeding from the hypothesis that auditory hallucinations in psychotic patients have another biological basis than hallucinations provoked by hypnotic suggestion in healthy persons, we performed a symptom-comparative study by means of 99mTc HMPAO single photon emission computed tomography. The results confirm the importance of pathogenesis in symptom-oriented psychiatric research. PMID- 2259716 TI - Attitudes of selected radiographers toward AIDS. AB - Acquired Immune Deficiency Syndrome (AIDS) has become one of the most important public health issues in America. This study examined the attitudes of 300 radiographers toward the medical and social issues of AIDS. Respondents supported disclosure of AIDS results to persons having contact with AIDS patients and mandatory testing for certain groups at risk to infection by the AIDS virus. Those having more exposure to AIDS patients appeared to have more tolerant attitudes toward the issues. PMID- 2259717 TI - Exposure reduction in panoramic radiography. AB - Increased receptor speed in panoramic radiography is useful in reducing patient exposure if it doesn't substantially decrease the diagnostic quality of the resultant image. In a laboratory investigation four rare earth screen/film combinations were evaluated ranging in relative speed from 400 to 1200. The results indicated that an exposure reduction of approximately 15 percent can be achieved by substituting a 1200 speed system for a 400 speed system without significantly affecting the diagnostic quality of the image. PMID- 2259718 TI - The saline solution bag as a compensating filter. AB - For certain radiographic procedures, extremes in tissue composition and/or thickness can result in a poor quality image. There exists, however, a practical approach to adjust for tissue extremes by using a saline solution bag as a compensating filter. By applying this technique, radiographic image quality can be improved. PMID- 2259719 TI - The relationship of ACT and ARRT test results. AB - This study examines the relationship between pre-admission American College Test composite scores and the American Registry of Radiologic Technologists examination results for one two-year technical college program. The resulting modification of program admission criteria and its effect upon ARRT exam results are discussed. PMID- 2259720 TI - More hot blood. PMID- 2259721 TI - [Is optical microscope capable of measuring everything?]. PMID- 2259722 TI - [Electron microscopy for study of biological function]. PMID- 2259723 TI - [X-ray microscopy for study of biological function]. PMID- 2259724 TI - [Optical two dimensional imaging of neural activity]. PMID- 2259725 TI - [Confocal laser scanning microscopy; theory and practice]. PMID- 2259726 TI - [NMR molecularscope]. PMID- 2259727 TI - [Scanning tunneling microscope]. PMID- 2259728 TI - [Raman microscope for biological samples]. PMID- 2259729 TI - [Cancer metastasis and platelet aggregation]. PMID- 2259730 TI - [Protein-protein interactions on transcriptional regulation--concerned with adenovirus E4 gene]. PMID- 2259731 TI - [Ethical aspects of suicide]. PMID- 2259732 TI - [Psychiatric analysis of suicidal poisoning]. AB - Psychiatric analysis has been performed in 389 patients, 194 women and 195 men during one year (May 1st 1987 to June 30th 1988). The analysis involved the sociodemographic or clinical patterns as well as the motivation mechanisms and methods of suicide realization. It has been stated that major group of patients was 20 to 40 years old, both women and men. The free-condition state was more frequent than others among patients studied. Majority of patients have had only basic education and were occupationally working. Patients with personality disturbances and neurotic ones were more frequently observed than others. Among psychotic patients a majority was represented by schizophrenics and those with endogenic depression. The alcohol dependence as a cause of suicidal attempt was most frequently noted in men; moreover, the alcohol intake frequently accompanied the suicidal attempt. Patients of our Department were consecutively treated in psychiatric out-patient units, however, there was insufficient aid to the patients being in crisis situations. PMID- 2259734 TI - [Crisis intervention after suicidal drug poisoning]. PMID- 2259733 TI - [Psychological analysis of the causes of attempted suicide using toxic agents]. AB - The purpose of the study was to analyse the biological, environmental and personality causes leading to suicide attempts. The study included 168 patients after suicidal intoxication basing on anamnesis from subjects studied and members of their families. The intelligence quotient and electroencephalographical examination has also been performed in subjects studied. The main causes of suicidal attempts were the unproper familial and educational environment, the lack of close relations with members of family, the lack of adequate reference patterns of social roles, the lowered resistance against difficult situations and the tendency to impulsive actions in a part of subjects studied conditioned biologically. The frequent cause of suicidal attempt was in demonstration focusing the attentions of relatives on difficult problems arising from life situation. PMID- 2259735 TI - [Psychosocial conditions of psychotropic drug poisoning of patients treated in the Gdansk Toxicology Center]. AB - The purpose of the study was in analysis of both causes and social conditioning leading to attempts of self-intoxications by the use of psychotropic drugs. The study included 234 patients treated in the Gdansk Toxicological Center during years 1982-1987. In a majority, the intoxications referred to young subjects up to 30 year of age, more frequently women than men. Only 10% of subjects studied have had university education. The alcohol or drug dependence and various psychiatric disturbances has been noted in a majority of cases studied. The lack of real suicidal determination was characteristic pattern of group observed. PMID- 2259736 TI - [The role of psychotherapist in the treatment of patients hospitalized for suicidal poisoning]. PMID- 2259737 TI - [Motives and circumstances of repeated suicidal attempts by taking drugs]. AB - It has been found out that 45% of the Toxicology Clinic patients hospitalized by their suicide attempt had previous suicide attempts. Calculations have shown that there were 76 previous suicide attempts in all and that 48 (63%) among these were not followed by any psychological and/or psychiatric help. The most frequent reason of this was keeping the attempt secret from further environment. Among the persons repeating suicide attempts affective illnesses, brain damage and personality disturbances were more often diagnosed; mental disturbances of their parents and/or disruption of their families in their childhood in the cases of these patients were also more frequent. Collapse or loss of significant interpersonal relations was a more frequent motive for trying to take one's life with persons repeating suicide attempts. PMID- 2259738 TI - [Problem of successful referral for further therapy of patients after attempted suicide]. PMID- 2259739 TI - [The role of sociologists in the Acute Poisoning Clinic]. PMID- 2259740 TI - [Social determinants of attempted suicide]. AB - With the case histories as a basis, the sociodemographic characteristics were analyzed of patients admitted to the Clinical Toxicology Centre, Institute of Occupational Medicine, Lodz, with drug-involving self-poisonings. Besides, the most prevalent reasons for and motives of suicidal attempts were determined. The majority of patients were between 15 and 29 years of age. The suicidal attempts were found to be more frequent in women and the highest rate (48%) was reported in married couples. Among the reasons, the family problems dominated. The majority of patients regarded the suicidal attempt as an instrument; only a few reported a strong will to die. The case study indicate that in seeking reasons for suicidal attempts the family status and social situation should be considered. PMID- 2259741 TI - [Characteristics of self-destructive acts of patients from the Acute Poisoning Clinic]. AB - The study carried out in 100 patients who attempted suicide by taking narcotics and antidepressants revealed that at the moment of poisoning the patients did not have any will to die. On the contrary, they reported they were concerned by a will to have their social situation improved. It can be induced both by the circumstances of drug taking (time, drug dose, presence of other people) and the reports of the patients themselves. They did not regard themselves as willing to commit suicide. However the fact that they were unable to solve their problems in a socially acceptable way indicates that they should be provided with some support. This task can, and should be, undertaken by the personnel of the detoxication centre they are admitted to. PMID- 2259742 TI - Assessment and self-assessment. PMID- 2259743 TI - Integrated imaging: history and perspectives of a radiological school. Foreword. PMID- 2259744 TI - Computer assisted instruction: new perspectives in the implementation of the electronic book. PMID- 2259745 TI - Structural organization and development of the radiologic activity at the "Istituto di Radiologia" of the "Universita del Sacro Cuore" of Rome (1964-1987) with the history of the units by organ. PMID- 2259746 TI - Communication prerequisites in the science of imaging. PMID- 2259747 TI - A new methodology in teaching and research. PMID- 2259748 TI - Introducing integrated imaging in clinical medicine and teaching: an ongoing experience. PMID- 2259749 TI - Expert systems and artificial intelligence in teaching and as decision-making support in radiology. PMID- 2259750 TI - Distribution and partial characterisation of immunoreactivity to the putative C terminus of rat pancreastatin. AB - The presumptive C-terminal nonapeptide of rat pancreastatin was synthesised based upon the sequence of rat chromogranin A (CGA) analogous to that of porcine pancreastatin as contained within porcine CGA. Antisera were produced which were used to determine the qualitative and quantitative distribution of pancreastatin like immunoreactivity in rat tissues by immunocytochemistry and radioimmunoassay respectively. Pancreastatin-like immunoreactivity was most abundant in pituitary, adrenal, gastric corpus and thyroid with considerably lower levels detected in the remainder of the gastroentero-pancreatic system and brain. Immunoreactivity was localised exclusively in endocrine cells and the relative abundance of immunoreactive cells paralleled the levels obtained radioimmunometrically. Chromatographic characterisation of pancreastatin-like immunoreactivity revealed molecular heterogeneity. Immunoreactive peptides of similar size to synthetic rat pancreastatin were present in gastrointestinal tissues and thyroid. These data indicate a tissue specific processing of CGA in the rat. PMID- 2259751 TI - Effects of rat and chicken calcitonin gene-related peptides (CGRP) upon calcium metabolism in chicks. AB - In vivo effects of intravenously injected chicken(c-) and rat(r-) calcitonin gene related peptide (CGRP) upon plasma total (Cat), ionized (Cai) calcium, inorganic phosphate (Pi) and clearance of an acutely administered 45Ca label have been examined in chicks. Both peptides were hypercalcaemic in fasted chicks, unlike previously reported hypocalcaemic response in mammals. r-CGRP was hypercalcaemic at doses of both 0.26 and 1.31 nmol/100 g body wt, the lower dose produced a significant elevation of Cat one hour after injection into 12-h-fasted chicks, the upper dose had a similar effect at 20 min. Cai was also non-significantly elevated by r-CGRP. Pi was slightly increased by r-CGRP at both doses, 20 and 60 min after injection. c-CGRP produced a dose (0.26-4.17 nmol/100 g body wt) dependent elevation of Cat and Cai in 22-h-fasted chicks. A greater response was however seen in fed animals. Peak responses were observed 45 min after injection. c-CGRP (1.04 nmol/100 g body wt) caused a significant decline in plasma Pi (P less than 0.05) in fasted chicks. Pi was elevated in control fed animals compared with fasted controls. c-CGRP (1.04 nmol/100 g) did not effect plasma Pi in fed chicks. Whilst both peptides elevated plasma Ca, clearance of an acutely administered 45Ca label from plasma was greater in both r-CGRP treated 12-h fasted chicks and c-CGRP treated 22-h-fasted chicks. In contrast, the rate of 45Ca clearance in fed chicks was not affected by c-CGRP treatment. The differential effects of these peptides upon plasma 45Ca clearance and other plasma parameters of Ca metabolism, suggest a complex mode of action of the peptide upon avian Ca homeostasis, possibly involving direct actions upon kidney and bone. PMID- 2259752 TI - Extrapolation of animal toxicity to humans: interspecies comparisons in drug development. AB - Different methods for converting the dose-related toxicity of drugs from animals to humans are reviewed. Each method is analyzed with respect to its utility and limitations. Linear extrapolations from animals to humans based on body weight equivalence are shown to be inaccurate unless species-specific conversion factors are used. Extrapolations based on surface area equivalence are more accurate, do not require conversion factors, and may be used when pharmacokinetic data are not available. Ultimately, interspecies conversions are most reliable when pharmacokinetic data are available, assuming that toxic responses are comparable among species for similar blood levels. Two pharmacokinetic-based approaches may be used: direct use of plasma concentration or area under the concentration-time curve (AUC) and physiologically based pharmacokinetic (PBPK) models. PMID- 2259753 TI - Evaluation of the carcinogenic potential of pesticides. 2. Methidathion. AB - The carcinogen potential of methidathion, a dimethoxyorganic phosphorus pesticide and cholinesterase inhibitor, was evaluated by the Health Effects Division of the Office of Pesticide Programs using a consensus peer review process and the EPA's guidelines for risk assessment. Methidathion was categorized as a Group C (possible human) carcinogen based upon evidence of an increased incidence of benign and malignant hepatocellular tumors, alone and in combination, in a single study involving male Chr-CD-1 mice. The compound was not carcinogenic in female Chr-CD-1 mice in the same study or in Sprague-Dawley rats of either sex in a second study. Methidathion was not genotoxic in a variety of in vitro or in vivo tests designed to detect DNA damage, chromosome aberrations, gene mutations, and sister chromatid exchange. Although methidathion was identified as being structurally similar to two other organophosphate insecticides, prothidathion and lythidathion, no toxicological data were available on either of these agents for comparative purposes. The biological information on methidathion was reviewed by the agency's FIFRA Scientific Advisory Panel who agreed with the category C designation for methidathion. The data were not found to be sufficient to quantify human risk to methidathion. PMID- 2259754 TI - Evaluation of modified methods for determining skin irritation. AB - The premarket testing of household cleaning products for dermal irritancy is best achieved via human testing. Animal dermal irritation testing is generally limited to screening for possible dermal hazard of totally new or unique products or ingredients prior to human testing or to meeting regulatory requirements of government bodies. Alternatives to animal tests are being sought; however, until such time that these alternatives are identified, validated, and accepted by government bodies, the judicious use of animal testing remains a necessity. Modifications to standard animal skin irritation test procedures have been evaluated against human skin irritation results with the objective of defining one method that could be used in place of current standard procedures that differ slightly from one another, and thereby avoid excessive and redundant use of animals. Hill Top Chambers (19 mm) and standard gauze patches (U.S. Department of Transportation procedure) were used to obtain comparative irritation responses for 24 cleaning products, common caustics, and acids in rabbits and humans. Exposure times were 1 or 4 hr, and responses were graded over a 72-hr period. Results indicate that use of the Chamber offers the potential to (1) reduce the number of animals used for skin irritation screening (smaller group size and up to eight test substances/concentrations per animal); (2) eliminate the need for conducting multiple tests to satisfy different governmental requirements; and (3) reduce animal stress by reducing exposure times without compromising the value of the irritancy patch test as a screening tool. When animal data are required, it is suggested that the use of a Chamber and other modifications of traditional test procedures offers advantages that could result in using fewer animals and/or have less potential for producing unnecessarily severe responses in animals. PMID- 2259755 TI - Interspecies comparisons in toxicology: the utility and futility of plasma concentrations of the test substance. AB - A classical dilemma in toxicology is how the dose administered relates to the dose delivered to the target site. Plasma concentrations of the test substance may be misleading since the concentration of any given substance in the plasma may not be representative of its concentration in tissues. Furthermore, a given tissue concentration of a xenobiotic can evoke responses which are highly species dependent. While evaluating toxicity data within one species, plasma concentrations reflect the effects of route of administration, bioavailability, dose level, multiple dosing, age, gender, etc. However, when toxicity data is compared across species, the relevance of plasma concentrations depends on the nature of the toxicity. Reversible, pharmacodynamic effects often correlate with plasma concentrations, although there may be marked interspecies differences in dose-response relationships. Irreversible effects, if pharmacodynamic in origin, often correlate better with the intensity/duration of the pharmacodynamic response, rather than with plasma concentration. On the other hand, irreversible effects, if chemically mediated, may not correlate at all with plasma concentration, the lesions being caused by reactive metabolites of fleeting existence, which rarely survive long enough to leave their site of synthesis. They cannot be measured in the plasma nor predicted from plasma concentrations of the parent xenobiotic. The limitations of plasma concentrations in interpreting the toxicology of substances which are tissue-sequestered, which are subject to pharmacogenetic factors, or which show plasma concentrations that are not proportional to dose are also discussed. Mention is made of possible alternatives to plasma concentrations in assessing exposure in toxicology studies. PMID- 2259756 TI - Fish consumption advisories: toward a unified, scientifically credible approach. AB - A model is proposed for fish consumption advisories based on consensus-derived risk assessment values for common contaminants in fish and the latest risk assessment methods. The model accounts in part for the expected toxicity to mixtures of chemicals, the underlying uncertainties in the health and exposure data, and the amount of contaminated fish consumed. Application of the model to a larger number of chemicals is possible. Noncancer toxicity is used as an example, but this model is applicable for risks from cancer as well. A second related model is proposed that is useful for comparing potential risks among sites (e.g., rivers and lakes). PMID- 2259757 TI - Harmonization of guidelines for toxicity testing of pharmaceuticals by 1992. AB - In the past there has been considerable disagreement between various regulatory authorities regarding the type and design of animal tests that should be required before a new medicine can be used ethically and safely in the clinic. However, regulatory variations have largely been removed within politically and geographically similar regions (e.g., the U.S.A., the European Community, the Nordic countries) and there now appears to be a consensus regarding the value of harmonizing international requirements. In order to assist the process of harmonization, a detailed table of preclinical toxicity requirements in the U.S.A., Canada, Japan, and the European Community for each test (acute, subacute, chronic, carcinogenicity, mutagenicity, reproduction) has been compiled. This has been circulated to the relevant regulatory authorities to ensure that it accurately reflects current requirements. The major differences between authorities were found to be the duration of chronic, repeated-dose tests and the design of reproduction studies. International pharmaceutical companies were asked to complete a questionnaire, indicating how they design their preclinical testing program to comply with varying regulatory requirements. Most of the respondent companies indicated that chronic tests of longer than 6 months were conducted solely to comply with some regulatory requirements. Many companies repeat reproduction studies in order to comply with Japanese requirements. This emphasizes the need to harmonize these guidelines and discussions are currently underway to attempt to develop protocols acceptable to the FDA, the EC, and the Japanese Ministry of Health and Welfare. PMID- 2259758 TI - Increased renal parenchymal echogenicity: causes in pediatric patients. AB - The authors discuss some of the diseases that cause increased echogenicity of the renal parenchyma on sonograms in children. The illustrated cases include patients with more common diseases, such as nephrotic syndrome and glomerulonephritis, and those with rarer diseases, such as oculocerebrorenal syndrome. Hyperechogenicity is a nonspecific finding but a significant one in that it suggests the presence of renal abnormalities. When it is demonstrated, further investigation is usually warranted. PMID- 2259760 TI - Improved tool for testing screen-film contact in mammography. AB - Good screen-film contact is essential to obtain high definition in radiographic images. We compared the conventional test tool for measuring screen-film contact, which uses #8 mesh (eight wires per inch [about three wires per centimeter]), with a prototype tool of #40 copper mesh. The conventional tool did not adequately test screen-film contact for mammography, in which significantly higher resolution is obtained. We believe #40 copper mesh should be used to test screen-film contact of mammographic cassettes. We also found that entrapped air may reduce screen-film contact and, therefore, recommend that cassettes be loaded at least 15 minutes before they are exposed. PMID- 2259759 TI - Anatomic variations and abnormalities in the diaphragm seen with US. AB - The authors report their experience with diaphragmatic structures that simulate intrahepatic masses at abdominal ultrasonography (US). In a series of 74 patients, diaphragmatic slips were the most common finding (34 patients). The slips could be differentiated from masses by scanning along their long axis to demonstrate elongated structures with multiple linear echoes. Scalloping of the diaphragm, associated with multiple slips, was seen in 10 patients. Partial eventration was found in 23. Inversion of a hemidiaphragm, caused by a large pleural effusion or intrathoracic mass, was seen in 13 patients. Pleural masses affecting the diaphragm were seen in 13 patients; focal hypertrophy of a diaphragmatic crus simulated a mass in three. Real-time US allowed the differentiation of diaphragmatic abnormalities from lesions. PMID- 2259761 TI - The retrotracheal triangle. AB - The retrotracheal triangle is an area in the posterior superior mediastinum where abnormal structures may be detected in as many as 2% of chest radiographs. The authors describe the anatomy of this space and the abnormalities found therein, including vascular abnormalities (aberrant right subclavian artery, right aortic arch, double aortic arch, true and false aortic aneurysms), thoracic duct lesions, esophageal abnormalities (benign and malignant tumors, congenital atresia, duplication cysts, foreign bodies, diverticula, and achalasia), and miscellaneous entities (intrathoracic thyroid, bronchogenic cyst, bronchogenic carcinoma, cystic hygroma, and emphysema). Careful attention to this long neglected area on chest radiographs can yield findings of abnormalities not otherwise suspected. PMID- 2259762 TI - Carcinoids of the gastrointestinal tract. AB - Carcinoids are tumors of the diffuse endocrine system. They occur most frequently in the gastrointestinal tract. Although they are considered malignant, their biologic behavior varies. The radiologic and pathologic appearances of gastric, duodenal, ileal, appendiceal, and rectal carcinoids are presented. PMID- 2259763 TI - Case of the day. Pediatric. Idiopathic retroperitoneal fibrosis. PMID- 2259764 TI - Case of the day. Ultrasound. Congenital cirsoid renal arteriovenous malformation (AVM) involving the lower pole of the right kidney. PMID- 2259765 TI - Case of the day. General. Oncocytoma of the right kidney. PMID- 2259766 TI - Case of the day. General. Gallstone perforation of the terminal ileum with abscess formation. PMID- 2259767 TI - Highlights from the history of mammography. AB - The evolution of mammography from simple radiography of mastectomy specimens to the foremost method of breast cancer screening has been dependent on its creators and nurturers, people with intense vision, idealism, and scientific skill. Society owes these investigators a debt of gratitude that can never be adequately repaid. PMID- 2259768 TI - Value of mammographic screening: assessment of studies and opinion. AB - The purpose of mammographic screening is to improve patient survival by detecting cancer at an earlier, more curable stage than is possible with physical examination. Three major studies have been used to assess the effect of mass screening on the survival rates and mortality for patients with breast cancer: the Breast Cancer Detection Demonstration Project, the Health Insurance Plan study, and the study conducted by the Swedish National Board of Health and Welfare. The author reviews these studies, describes statistical biases (lead time, length time, patient self-selection, and overdiagnosis) to be considered in study design and analysis, and discusses briefly risks versus benefits of mammography. PMID- 2259769 TI - Non-Hodgkin lymphoma of the small intestine. AB - The authors present a simplified radiographic classification of non-Hodgkin lymphoma involving the small intestine. The classification system is based on radiographic findings in 22 pathologically proved cases of lymphoma involving the small bowel and consists of three major forms: primary, lymphoma complicating celiac disease, and mesenteric nodal. In this series, small bowel lymphoma was evenly distributed in the jejunum and ileum. The most common radiographic patterns were circumferential lesion (seven cases), cavitary lesion (four cases), and mesenteric nodal disease invading the small bowel (seven cases). Obstructive symptoms were usually encountered with the mesenteric nodal form. Lymphoma complicating celiac disease was typified by multiple, thickened, nodular folds involving a segment of proximal small intestine. PMID- 2259770 TI - CT appearance of uterine leiomyomas. AB - Uterine leiomyomas, commonly known as fibroids, are one of the most common pelvic tumors found in women. Ultrasonography is the primary modality for evaluating leiomyomas. However, frequently these tumors are not accompanied by symptoms, and they are found incidentally during computed tomographic (CT) examinations performed for other indications. Because leiomyomas may first be noted on CT scans, radiologists should become familiar with their characteristic appearance. The authors describe the CT findings of uterine leiomyomas and their secondary changes, including cystic degeneration, calcification, infection, necrosis, fatty degeneration, and sarcomatous degeneration. PMID- 2259771 TI - [Ceramo-metal restorations for devitalized teeth receiving non-alloy crowns 2]. PMID- 2259772 TI - [Carbon-epoxy composite cores]. PMID- 2259773 TI - [Hematophagous activity of Anopheles vestitipennis Dyar & Knab, 1906 (Diptera: Culicidae)]. AB - The hematophagic activity of Anopheles vestitipennis Dyar and Knab, 1906, was studied in a rural locality during the dry and rain seasons, through inside and outside home collects with human bait at a schedule form 19:00 to 07:00 hours. The species showed preference by inside home food (endophagic) in both seasons. There was 2 maximum activity peaks inside of the buildings, from 23:00 to 24:00 hours and from 02:00 to 03:00 hours (the first one agrees with the peak occurring outside). During the dry season the activity peak outside occurred from 24:00 to 01:00 hours; while inside occurred from 02:00 to 03:00 hours. PMID- 2259774 TI - [Indirect immunofluorescence in filariasis. I. Standardization of the technique. Cuba, 1983]. AB - Indirect immunofluorescence was standardized for the diagnosis of human filiariae, using antigens of Dipetalonema viteae. Due to the determined sensibility and specificity, the tier of 1:512 was recommended for aiding clinicians in the individual diagnosis of suspicious patients and that of 1:256 for epidemiologic studies. The titers of cross reactions were less than 1:128. PMID- 2259776 TI - [Water pollution and presence of Anopheles albimanus Wiedemann, 1821 and Culex nigripalpus Theobald, 1901]. PMID- 2259775 TI - [Yersinia enterocolitica: investigation in 1,300 children under 5 years of age with acute diarrhea]. AB - The presence of Yersinis enterocolitica was investigated in feces of 1,300 children younger than 5 years, hospitalized because of presenting acute diarrheic disease in Cuba during 1985-1988 period at different provincial pediatric hospital, as well as in Havana City. Selective agar base for Yersinia was used supplemented with cephsuloidin, Irgasan and novoviocin (CIN) and buffered saline solution as enrichment medium. This last one at 4 degrees C during 21 days with weekly resowings to the selective medium. Isolation of Yersinia enterocolitica was not obtained in any of the patients under study. PMID- 2259777 TI - [Reproduction of the larvivorous fish Poecilia reticulata (Poeciliidae) in natural conditions]. AB - The main reproduction characteristics of the larvivorous fish Poecilia reticulata, were determined under natural conditions. The study was carried out in a ditch of dirty water sink at the Lenin Park (Havana City) in the period comprised between November 1986 and May 1987. The samplings were performed monthly, and the presence of gravid females was demonstrated during the whole period, while the average of embryo/female increased remarkably during April. Such results contribute to the knowledge of the biology of this fish for its better use in the biologic control of mosquito larvae. PMID- 2259778 TI - [Serotyping of strains of non-tuberculous mycobacteria]. AB - Forty strains of mycobacteria, belonging to Mycobacterium-avium-intracellulare scrofulaceum complex, isolated from symptomatic respiratory patients, were studied. For such study, agglutination-adsorption technique was applied, using specific antisera elaborated at the "Pedro Kouri" Institute of Tropical Medicine, National Reference Institute, with titers ranging close to 1:320. The results obtained demonstrated that the prevailing types were those of the species Mycobacterium intracellulare (31 strains), prevailing serotypes 9 (Darden), 8 (Davis), 12 (Haweel) and serotype 26 followed by the species M. avium (3 strains) and M. scrofulaceum (2 strains). PMID- 2259779 TI - [Automated System of Control of International Travellers]. PMID- 2259780 TI - [Microbiologic aspects of bacteremia in patients hospitalized in the intensive care unit]. AB - The microbiologic aspects of the bacteriemia were prospectively studied in patients hospitalized in a pediatric Intensive Care Unit. Thirty six episodes of bacteriemia were detected in 29 patients. Secondary bacteriemia prevailed on the primary ones. The most frequent infectious foci associated with bacteriemia were the infections of respiratory tract, followed by intravascular catheterism. The microorganisms more frequently associated with bacteriemia were: Haemophilus influenzae, Staphylococcus epidermidis, Eacherichia coli and Pseudomonas seruginosa. PMID- 2259781 TI - [Identification of microorganisms of the Vibrio genus using the method of sample combination]. AB - In order to apply a more rapid, economic and effective method for the isolation of microorganisms of the genus Vibrio. 400 samples of feces from passengers hospitalized at the "Pedro Kouri" Tropical Medicine Institute, Searching Ward, were processed by the combination method. In this study the feces were grouped in combinations of ten; in this way 40 coprocultures were performed. The isolation was carried on enriching the samples in alkaline peptone at pH 8.6 and subcultures in thiosulfate citrate bile salts sucrose agar were performed. PMID- 2259782 TI - [Various psychosocial and epidemiologic characteristics of leprosy in the Artemisa municipality]. AB - Psychosocial and hygienico-epidemiologic characteristics of prevalence of leprosy in Artemisa Municipality, Havana Province, were studied and compared with a control group. In relation to psychical stability, they are normal individuals. The general personal profile shows a personality structure disposed to neuroticism. The hygienic conditions are good. The majority of patients does not feel marginated and they have been incorporated to social and labor life. There are not mutilating incapacities in these patients. All needed of rehabilitation have it. The patients, in this municipality, know the main aspects of the disease. PMID- 2259783 TI - [Indirect immunofluorescence in filariasis. III. Comparison of microfilaremia and treatment. Cuba, 1983]. AB - Twenty six patients coming from endemic areas, with diagnosis of filariasis caused by Wuchereria bancrofti, Loa loa and Manzonella (Dipetalonema perstans) and 29 patients suspicious of suffering filariasis were studied by means of Knott, membrane filter and indirect immunofluorescence techniques. Results of microfilaremia were compared with antibody titers and it was verified that there was not relationship between these parameters. The suspicious patients presented higher antibody levels than those of the verified patients. In additions, a preliminary study was carried out on the serologic behaviour of some patients treated with diethylcarbamazine (6 mg/kg daily, during 14 days) and increase of antibody titers was observed in most of the cases after three days and a decrease after the first month of treatment. PMID- 2259784 TI - [Malaria imported to Cuba]. PMID- 2259785 TI - [Aspects of larval density of Culex nigripalpus Theobald, 1901 (Diptera: Culicidae) in natural conditions]. AB - A study was carried out in order to determined the larval population density of Culex nigripalpus, vector of different parasitic and viral diseases in the neotropical region. Two population from Havana and Havana City Provinces were studied during the period comprised between November 1986 and November 1987. The higher densities of this species appeared during December 1986 (838.2 larvae/m2) and November 1987 (495 larvae/m2) in Santa Cruz del Norte (Havana) and in November 1986 (343.2 larvae/m2), January 1987 (232.65 larvae/m2), February 1987 (580.8 larvae/m2) in the Lenin Park (Havana City). PMID- 2259786 TI - [Mode of inheritance of malathion resistance in Culex (C.) quinquefasciatus Say, 1923 (Diptera: Culicidae)]. AB - Crossings and retrocrossings were performed between S-Lab. and "Quibu" strains of Culex quinquefasciatus Say, 1823. It was found that resistance to malathion was dominant inherited in an incomplete and monofactorial form. PMID- 2259787 TI - [The first certain case of Diphyllobothrium latum in Cuba]. AB - The first certainty case of Diphyllobothrium latum in Cuba, is described. The diagnosis is based on the identification of proglottids, which shows the typical characteristics of this cestode. PMID- 2259789 TI - Maximal diffusion-distance within skeletal muscle can be estimated from mitochondrial distributions. AB - Mitochondrial volume density (Vv [mit]) distributions were measured with a test pattern of concentric rings centered upon randomly chosen capillaries in oxidative skeletal muscle cells of two Antarctic fishes, Trematomus newnesi and Notothenia gibberifrons. Vv(mit) in both species was highest in the ring closest to the capillary, minimal further from the capillary (at a distance that was characteristic for each species), and rose in the annuli furthest from the capillary. Plots of Vv(mit) against total area between each ring and the central capillary fit the form of a second-order polynomial (r2 greater than 0.9). If PO2 or blood-borne metabolite concentration predicates the pattern of Vv(mit) distribution, minimal Vv(mit) is at the same position as the minimum in concentration or gaseous partial pressure of capillary-supplied commodities. This minimum is the boundary between cylinders of tissue being supplied by adjacent capillaries, and thus delineates the maximal diffusion-distance for capillary supplied commodities. Maximal diffusion-distance (microns) for T. newnesi = 26.23 +/- 1.64; N. gibberifrons = 21.45 +/- 0.51. For O2, maximal diffusion-distance conventionally is referred to as Krogh's radius, R. With an easily obtained estimate of numerical capillary density, these R values can be used to calculate a capillary tortuosity constant (c[k,0]) and capillary length density (Jv[c,f]). c(k,0) values were also determined using an established method, and R and Jv(c,f) values calculated from these values did not significantly differ from values determined from mitochondrial distributions. Mitochondrial distribution analysis may more accurately reflect changes in capillary blood flow and heterogeneity of diffusion and solubility constants within muscle than currently existing techniques. Similar distributions of Vv(mit) reported for several species of vertebrates suggest wide applicability of the method. PMID- 2259788 TI - [Evaluation of an anti-influenza vaccine in a group of elderly]. AB - To 57 individuals of the Old People's Home in Guines and Artemisa Municipalities, without vaccinal contraindications, was administered and inactivated bivalent antigrippal vaccine with the antigenic content: A/Kiev/59/79 (H1N1) and A/Filipina/2/82 (H3N2). Trough the inhibition technique of hemagglutination in pair sera, satisfactory results (seroconversion) were obtained in more of the vaccinated individuals, for both antigens. Local reactions such as erythema and papule were observed. Nine patients were detected among the vaccinated individuals by the epidemiologic surveillance carried out a year after vaccination. The serologic study performed to five of them showed a case positive to influenza A (H3N2) and another one positive to influenza B. PMID- 2259790 TI - Adjustment of DLCO for varying COHb, and alveolar PO2 using a theoretical adjustment equation. AB - The diffusing capacity of the lung for carbon monoxide (DL) is affected by changes in alveolar partial pressure of oxygen (PAO2), hemoglobin concentration (Hb), and carboxyhemoglobin concentration (COHb). A number of investigators have derived empiric adjustment equations to account for changes in these variables. We evaluated an adjustment of DL for changes in COHb and PAO2 using a single equation derived from Roughton and Forster's original definitions (J. Appl. Physiol., 1957). Unadjusted DL values declined significantly with rising COHb ( 0.938%/percent COHb increase, P less than 0.0001) and rising PAO2 (-0.343%/mm Hg PAO2 increase, P less than 0.0001). Adjusted measured DL using the derived equation showed no significant change with changing COHb and PAO2 levels and provides an acceptable method for adjustment of DL for the effects of varying COHb and PAO2 levels from the standard conditions of COHb% = 0, and PAO2 = 110 mm Hg. Since a similar equation has previously been used to adjust for changes in DL due to anemia, we propose to use a single equation which is theoretically derived and empirically verified to adjust DL measurements for changes in COHb, PAO2 and hemoglobin. PMID- 2259791 TI - Effect of alveolar pressure on single-breath CO diffusing capacity at mid-lung volume. AB - The present study examines whether changes in the alveolar pressure (PA) affect the single breath diffusing capacity for carbon monoxide (DLCO) more strongly at mid-lung volume than at total lung capacity (TLC) in normal subjects. DLCO was measured at 60%, 80% and 100% of TLC, while PA was kept at +30, 0, or -30 cm H2O by the subject's effort during the measurement of DLCO at each lung volume. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were also determined. DLCO at zero PA was found to be higher at 100% TLC than at lower lung volumes. At PA = +30 cm H2O, DLCO at 100%, 80%, and 60% TLC decreased by 8%, 13%, and 13%, respectively, and the decreases in Vc were 2%, 10%, and 21%, respectively. However, negative PA did not cause any significant changes in DLCO or Vc at any lung volume. Also, Dm did not change at any PA. We conclude that DLCO is more affected by a positive PA at mid-lung volume than at a high lung volume, probably due to a greater decrease in Vc. PMID- 2259792 TI - Abdominal muscle activity in conscious dogs: effect of sleep and route of breathing. AB - Abdominal muscle activity (EMGabd) was studied in 4 adult dogs during wakefulness and sleep. The dogs were previously prepared with a permanent side-hole tracheal stoma, and were trained to sleep with a tightly-fitted snout mask, hermetically sealed in place. They breathed either through a cuffed endotracheal tube inserted distally into the tracheal stoma (tracheal), or through the upper airway, with the tracheal stoma plugged (nasal). Sleep state was determined by behavioural, electroencephalographic and electromyographic criteria. EMGabd activity was measured using fine bipolar needles inserted into the abdominal muscle layers. Expiratory EMGabd augmented progressively from sleep onset to SWS regardless of route of breathing, and without major changes in the animal's ventilation. Maximal EMGabd occurred in SWS during nasal breathing; EMGabd increased from a mean of 16.6 +/- 0.3 mV awake, to 23.8 +/- 0.3 mV in SWS, representing an overall increase of 55.0 +/- 7.5% from the awake level. EMGabd increased similarly during tracheal breathing, with an overall increase of 62.0 +/- 15.4% in SWS. We conclude that the consistent augmentation of expiratory EMGabd activity in sleep indicates that expiration in the dog is an active process, which is enhanced during nasal breathing and NREM sleep. PMID- 2259793 TI - Time course of laryngeal aperture response to expiratory resistance loading in humans. AB - Expiratory laryngeal restriction in normal humans is augmented immediately following expiratory flow resistance loading applied to the mouth. The time course of this increased narrowing reflects the dynamics of the physiological stimuli that govern laryngeal control during expiration. Lung volume, expiratory airflow and upper airway pressure are possible factors influencing the larynx, and a comparison of their dynamics with those observed for laryngeal narrowing during control and loaded expirations ought to indicate the possible contribution of each source. We examined the dynamics of lung volume, airflow and laryngeal aperture subsequent to single breath applications of small flow resistance loads (2 and 5 cm H2O.L-1.sec) in 3 subjects using video image analysis techniques to define accurately the laryngeal aperture variation with time. The earliest deviation of the loaded expired volume time course from the control trajectory lagged the earliest occurrence of a significant increase in laryngeal narrowing with the larger load. Augmented laryngeal narrowing occurred simultaneously with deviation of the expired flow from the control trajectory. The responses to the smaller load were noisier, but were consistent with the hypothesis that information other than lung volume modulates the early laryngeal response to these loads, and receptors responding to the rate of change of lung volume (airflow) and/or upper airway pressure may be involved. PMID- 2259794 TI - Influence of dehydration and watering on camel red cell size: a scanning electron microscopic study. AB - Three young female camels were subjected to an eleven day period of dehydration followed by a single large drink. Blood haematocrit and plasma protein concentration were monitored regularly during dehydration and for 48 h following watering. Blood samples were taken at regular intervals, before and after watering, and prepared for scanning electron microscopy (SEM) for analysis of red cell size and shape. Plasma protein concentration did not change rapidly on watering implying that the camel has homeostatic mechanisms which regulate plasma osmolarity by controlling the rate at which large volumes of water are absorbed on drinking. By SEM, camel red cells were elliptical in shape with mean surface dimensions of 6.5 microns x 4.0 microns with an estimated minimum thickness at mid point of 0.95 microns: neither their shape constant nor size changed on dehydration or watering corroborating the absence of major and rapid changes in osmolarity. PMID- 2259795 TI - Pulmonary and cutaneous oxygen uptake and oxygen consumption of isolated skin in the frog, Rana pipiens. AB - Oxygen uptake and consumption rates were measured in intact and isolated skin from the amphibian Rana pipiens to determine the percentage of total cutaneous O2 uptake that is consumed by the skin itself. Paired measurements, using open respirometry, were done on intact and isolated skin. In normoxic water oxygen uptake across the cutaneous surface was always greater than O2 consumed by isolated skin. Closed respirometry was used to determine the effect of declining water PO2 on cutaneous uptake across intact skin and oxygen consumption by the isolated skin. Both intact skin uptake and isolated skin consumption were related significantly to water PO2 (150-100 mm Hg). Assuming O2 consumption of the isolated skin to be same as in situ, calculations showed that when water PO2 was high (150 mm Hg), about 40% of total cutaneous O2 uptake was consumed by the skin. At low PO2 (100 mm Hg) this figure was about 20%. Thus in the face of declining water PO2, a greater percentage of total cutaneous uptake goes to satisfy the oxygen requirements of other tissues. PMID- 2259796 TI - Temperature effects on metabolism, ventilation, and oxygen extraction in a Neotropical bat. AB - We examined the relationship between ambient temperature (Ta), body temperature (Tb), oxygen consumption (VO2), carbon dioxide production (VCO2), evaporative water loss (mH2O), respiratory frequency (f), tidal volume (VT), minute volume (VI), and oxygen extraction (EO2) in the Neotropical bat Noctilio albiventris (mean mass 40 g). The factorial aerobic scope was 7.2 between Ta of 1-35 degrees C (VO2 = 0.119 and 0.0165 ml/(g.min), respectively). The respiratory exchange ratio (VCO2/VO2) did not change with Ta and mH2O was constant between Ta of 10-35 degrees C. Thermal conductance was minimal at 30 degrees C and constant and low at Ta less than 30 degrees C. Between 10 and 35 degrees C, Noctilio accommodated changing VO2 with parallel and roughly equivalent changes in f, VT, and EO2. The change in VO2 between 10 and 1 degrees C was accommodated mainly through changing f. Ventilation parameters in resting thermoneutral Noctilio are intermediate between allometric values for birds and mammals. Maximal EO2 in Noctilio (35-40%) is higher than for other mammals but considerably less than maximal EO2 in some birds. PMID- 2259797 TI - Respiratory effects of cold-gas breathing in humans under hyperbaric environment. AB - Changes in total lung resistance (RL) during inhalation of cold gas mixtures were measured in 4 human volunteers during an experimental dive at 46 ATA. The subjects breathed helium-nitrogen-oxygen mixtures during the decompression schedule, and measurements were performed at 46, 36, 21, 12.5, 6 and 2 ATA (1 ATA = 100 kPa). RL was measured during eupneic ventilation when individuals inhaled either ambient gas at +30 to +33 degrees C (control condition), or cooled gas at +7 to +18 degrees C. RL values measured in control conditions increased with gas density. Thus, the changes in RL induced by cold gas breathing were expressed in percent of the corresponding control values. No cold-induced bronchospasm occurred at low ambient pressure, even at the lowest inspired temperature, +7 degrees C. However, the airway response was present at pressure up to 21 ATA and then occurred at higher level of inspired gas temperature. The convective respiratory heat loss (Cr), calculated at each pressure level and experimental condition, was linearly related to cold-induced changes in RL; the value of Cr inducing 20% increase in RL was around 1.4 kcal.min-1. The bronchomotor response was related to the increase in respiratory heat loss induced by the high thermal capacity of the gas mixture used in hyperbaric environment. The present observations confirm previous data obtained under hyperbaric conditions (25 ATA) as well some experiments performed at sea level in normal individuals breathing very cold air. PMID- 2259798 TI - Psychiatric syndromes associated with neurologic disease. PMID- 2259799 TI - Conversion symptoms revised. PMID- 2259800 TI - Organic delusional syndrome. AB - Delusions may be the most prominent manifestations of brain dysfunction, and a host of medical and neurologic conditions can present with or produce delusions. Recognition of the underlying disorder frequently aids in successful treatment. Comparison of organic delusional syndromes with schizophrenia suggests that limbic system abnormality and dopamine dysfunction are common underlying factors shared by different causes of delusions. PMID- 2259801 TI - Depressive syndromes associated with diseases of the central nervous system. PMID- 2259802 TI - Depression following cerebrovascular lesions. PMID- 2259803 TI - Psychiatric and cognitive aspects of multiple sclerosis. PMID- 2259804 TI - Psychiatric consequences of basal ganglia disease. PMID- 2259805 TI - The neuropsychiatry of human immunodeficiency virus. AB - With the advent of HIV infection, a new causal group of neurobehavioral disorders has emerged. These are the neurogenic and psychogenic neurobehavioral disturbances associated with HIV. Neurogenic disorders are those caused by the direct effects of HIV on the CNS, or by other infectious agents, neoplasms, vascular events, or side effects of biologic treatments in HIV-infected persons. Psychogenic disorders include anxiety, depression, adjustment reactions, and other behavioral disturbances related to knowledge of HIV seropositivity and recognition of being afflicted with a serious illness. In many instances, the psychogenic disorders appear to represent recrudescences of preexisting psychopathology. The comprehensive management of the patient with HIV infection requires early recognition and proper treatment of such complications. PMID- 2259806 TI - The brain in schizophrenia. AB - Schizophrenia has been the subject of intensive neuropsychologic, neuroradiologic, neuropathologic, and neurochemical investigations. The most consistent and reproducible result from all this effort has been the demonstration of a mild degree of enlargement of the cerebral ventricles. The existence of this finding is no longer a subject of controversy, and it clearly occurs independently of psychiatric treatment and chronicity of disease. This finding represents the strongest evidence to date that a structural lesion of the central nervous system underlies schizophrenia. The localization of the lesion responsible for ventricular enlargement and for the clinical findings in schizophrenia is not as clear. Pathologic alterations in the anteriomedial temporal lobe, particularly in the hippocampus, have been independently identified by several groups, using both in vivo neuroimaging and postmortem anatomic techniques. The details and etiology of temporal lobe-hippocampal pathologic states remain to be elucidated. Neuropsychologic and cerebral blood flow studies suggest that the frontal lobe is dysfunctional in schizophrenics. However, there is little known about the neuropathologic basis and neurochemical correlates of this deficit. One of the intriguing new hypotheses about the neurologic findings in schizophrenia is that they are the result of an abnormality in the early development of the brain. The possibility that the clinical illness is a delayed manifestation of this process, perhaps because of an interaction between the early developmental deficit and later maturing functional neural systems, is a subject of speculation. While much study has been devoted to the structural and functional abnormalities underlying schizophrenia, much remains to be discovered. In the past 20 years, the development and application of new techniques, including CT, MRI, rCBF, and PET, have revolutionized the study of schizophrenia, and have produced the first consistent neuropathologic findings in this disorder. The pace of discovery has been gradually accelerating. Application of new techniques and careful use of patient selection criteria will help further decipher the neurologic basis of this disorder. There is reasonable hope that by the end of this century, the pathology and pathophysiology of this common but baffling illness will be revealed. PMID- 2259807 TI - Psychopathology of frontal lobe syndromes. AB - In this review, some basic aspects of frontal lobe functioning have been discussed and methods of testing for frontal lobe abnormalities outlined. It has been emphasized that the frontal lobes are affected in a number of diseases, which cover a broad spectrum of neuropsychiatric problems. Furthermore, it is suggested that the frontal lobes are involved in syndromes not traditionally thought to be related to frontal lobe dysfunction, for example, schizophrenia, and rarer presentations such as misidentification syndromes. Frontal lobe dysfunction often goes unrecognized, especially in patients who have normal neurologic testing and apparently intact IQ when routine methods of investigation are employed. Although marked disturbances of behavior following frontal lobe dysfunction have now been described for well over 120 years, these large areas of the human brain, and their links with some of the highest attributes of mankind, have been relatively neglected and are worthy of much further exploration by those interested in neuropsychiatric problems. PMID- 2259808 TI - Neurologic side effects of psychiatric treatments. PMID- 2259809 TI - Neurology of aggression and episodic dyscontrol. PMID- 2259810 TI - The Salpetriere wives. PMID- 2259811 TI - [Visualized treatment objective: a simplified technique]. PMID- 2259812 TI - [New protocol for radiocinematographic study of extraprandial deglutition in the child]. PMID- 2259813 TI - [New edgewise appliance has arrived ... (1)]. PMID- 2259814 TI - [Clinical cases of transposition]. PMID- 2259815 TI - [3 years use of ceramic brackets]. PMID- 2259816 TI - [A canine when you have us!]. PMID- 2259818 TI - [Bonding of an anterior retaining arch]. PMID- 2259817 TI - [Dear parents, help us!]. PMID- 2259819 TI - [Premature placental detachment]. PMID- 2259820 TI - [Mycotic aneurysm of the abdominal aorta]. AB - Mycotic aneurysm of the abdominal aorta is an uncommon disease that carries a high mortality rate. In this report, two patients with this disease are presented. In the first case, Salmonella sp was cultured from an atherosclerotic aneurysm, and in the second patient, the aneurysm was a complication of Staphylococcus aureus bacterial endocarditis. Both presented suggestive clinical findings of the disease with fever, back pain, and pulsatile and expansive abdominal mass. The first patient was submitted to emergency aneurysmectomy with insertion of a dacron aorto-bi-iliac prosthesis and antibiotic therapy for a long period. He died two months after surgery due to upper gastrointestinal tract bleeding. The second patient was submitted to a successful and not yet described arterial reconstruction which included ligation of the aortic aneurysm and interposition of an aorto-bi-iliac sequential venous graft with reverse autologous saphenous vein. The authors consider this technique to be a good choice for the surgical treatment of mycotic aneurysm of the abdominal aorta particularly because it enables to avoid synthetic prosthesis. PMID- 2259821 TI - [Clinical and biochemical characterization of isoniazid-induced auto-antibodies]. AB - Isoniazid (INH) is one among many drugs capable of inducing autoantibodies and, in some cases, a lupus-like syndrome (LE). A longitudinal study was performed in 24 tuberculosis patients treated with INH to detect antibodies (A-AH) to total histones and fractions. Antinuclear antibodies were observed in two patients after treatment. Higher frequency of IgM-AH was also observed. IgM-AH binding to all fractions were observed in those serum samples exhibiting stronger ELISA reactivity. Conversely, binding to only H1 occurred when lower IgM-AH activity was tested. Correlations with clinical expressions of LE were not observed in the present study. PMID- 2259822 TI - [Hospital infections at an oncology hospital]. AB - During 23 months, the authors analyzed 8122 records of cancer patients admitted to the National Institute of Cancer of Rio de Janeiro, Brazil. The rate of hospital infection was of 18.4 infection episodes per 100 admissions. Hospital infections were detected in 556 patients (57.7%) of the surgical department. The overall rate of purulence seen in 4194 surgeries was 10.1%, and among 2153 clean surgeries, the authors found 95 (4.4%) suppurated surgeries. The surgical wound (28.2%), the respiratory tract (19.2%), and the urinary tract (18.7%) were the major sites involved during infections episodes. Of the 319 ICU patients evaluated, 154 acquired infection after the first 72 hours, with a mortality rate of 48.7%. The hospital microbial flora was made-up mostly of gram-negative aerobic bacteria, with a high incidence of micro-organisms that resist to major antibiotics of hospital use. The percentage of positive results in blood culture tests requested was of 23.7%, with a predominance of gram-negative bacteria (50.9%) and a high percentage of gentamicin-resistant micro-organisms. Antibiotics of greater use in surgical interventions were amikacin, first generation cephalosporins, and chloramphenicol, whereas amikacin, carbenicillin, and first and third generation cephalosporins prevailed in nonsurgical treatments. The authors' experience and findings re-emphasize the need and the importance of a broad multidisciplinary understanding and suggest the need of strict action for an effective control and prevention in hospitals of developing countries. PMID- 2259823 TI - [Retrospective analysis of the incidence of midline supratentorial neoplasms in children and young patients: craniopharyngiomas, hypophyseal and pineal neoplasms]. AB - The authors analyzed, in a retrospective study made at the Pathology Department of the Medical School of the University of Sao Paulo, 1632 cases of intracranial neoplasms in a period of 50 years (1931-1981). The investigation concentrated on 592 cases (36.2%) of patients with age ranging from 0 to 20 years. The overall number of craniopharyngiomas in this group was 21 (3.5%); 8 cases (1.35%) of hypophyseal neoplasms, and 4 cases (6%) of pineal neoplasms. Neoplastic infiltration of the hypophysis and pineal was present in 24 cases (4.0%). No metastases were observed. The description and importance of these findings, and their correlation with data from other authors are presented. PMID- 2259824 TI - [Sex determination in blood stains through identification of Y-chromatin: medico legal application]. AB - The Y-chromatin is visualized in human interphase nuclei, corresponding to the distal portion of the Y-chromosome, which shows marked fluorescence after staining with quinacrine. This report describes the results of sex determination on blood smears fixed in methanol and blood stains left at room temperature for 13 weeks (1st report), and for 10 months (2nd report). Blind trials showed that a reliable sex determination of blood stains on glass left for at least six months is possible. The application of this method in forensic practice is discussed. PMID- 2259825 TI - [Bronchodilation induced by fenoterol in asthmatic patients: comparison of jet nebulization and spacer device]. AB - OBJECTIVE: To compare bronchodilation attained by fenoterol administered through a jet nebulizer and through a spacer device. TYPE OF STUDY: Open, randomized. PATIENTS: 44 adults with asthma, peak-flow rate varying between 120 and 200 l/min. Patients were divided into two groups. TREATMENT [corrected]: Group A was treated with fenoterol (2.5 mg) with saline to complete 3 ml given through a jet nebulizer; 30 minutes later, an additional dose (1 mg) was given through a 500 ml spacer. Group B was treated with the same dosage, but the spacer [corrected] was used first. EVALUATION: Peak-flow meter in zero, 30 and 60 minutes. RESULTS: No significant difference in bronchodilation was seen between groups A and B. CONCLUSION: Fenoterol through a spacer can replace inhalation in adult asthma patients with non-severe obstruction. Lower cost and home treatment are the main advantages. PMID- 2259826 TI - [Depression in the elderly: a review]. AB - With the increase in life expectancy during recent years, the elderly population and its medical problems are increasing considerably. Depression in the elderly is an important example of this situation. In this article, the authors discuss special aspects of depression in the elderly, its clinical presentation, prevalence, course, etiologic factors, diagnosis, and treatment. They draw attention to the risk of not correctly identifying and treating those patients. PMID- 2259827 TI - Methemoglobinemia associated with loxoscelism. AB - In twenty five patients who presented the cutaneous form of loxoscelism, serum haptoglobin and lactic dehydrogenase, erythrocyte glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, methemoglobin, bilirubin and reticulocytes were investigated after bite. No hemolysis was detected but an increase in methemoglobin was found in 54% of the cases; in 7% it was between 1.1% and 2%, in 27% it ranged from 2.1% to 4%, and in 20% from 4.1% to 8%. Blood samples of a normal, blood group 0 individual and of a patient who exhibited methemoglobinemia after Loxosceles bite were incubated separately with antisera against Loxosceles gaucho, Crotalus terrificus, Bothrops jararaca, with Loxosceles gaucho venom and 0.3% phenol. No methemoglobin was found after 1, 4, 8 and 15 days in both sets of samples. At the 25th day all the samples, including the controls, exhibited similar methemoglobin reductase decrease. The data suggest that the methemoglobinemia which occurs in 50% of the patients probably arises from in vivo venom metabolism, inasmuch as the crude venom does not induce methemoglobinemia. PMID- 2259828 TI - [Serotypes of Streptococcus pneumoniae isolated from cerebrospinal fluid in 1977 1988 in Sao Paulo City, Brazil]. AB - Since 1977, the Instituto Adolfo Lutz (IAL) is having interest in the serotyping of S. pneumoniae or pneumococcus from infections caused by this bacteria. The isolated strains have been sent to the WHO Pneumococcal Reference Center, Pennsylvania, U.S.A.. From 1977 to 1988, 1.000 pneumococcus strains isolated from cerebrospinal fluid were typed, according to Danish nomenclature, and 60 serotypes were identified. The most frequent serotypes were 1, 6B, 18C, 14, 5, 3, 6A, 23F, 19F, and 38. Among different age groups, they showed a variable incidence, with serotype 6B in the ages of zero to almost 2 years old, serotype 1 in the age group of 2 to 50 years old, and serotype 3 in the ages over 50. During the 12 years study, 25 serotypes showed some uniformity in the frequency, the same as with the seasonal fluctuations. Concerning the severity of the pneumococcal infections, chiefly meningitis, and the few information related to pneumococcus serotypes which occur in the area, it was considered of high relevance to have the information of serotypes, once polysaccharide vaccines have been employed with success to prevent these infections. PMID- 2259829 TI - [Schistosoma mansoni: quantitative aspects of the fertility and survival of worms of irradiated cercariae (3 Krad), in mice]. AB - The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus), experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains), by transcutaneous route. The cercariae used were a) non-irradiated (control groups), and b) irradiated with 3 Krad of gamma irradiation (Co-60). From the 33rd day on, some stability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90th day), notedly in relation to the LE strain. Thus, it was concluded that gamma irradiation (at the dose of 3 Krad) is able to hinder the worm egg production in 98.1% of the infected mice. Further, it was observed that the few detected eggs were dead. Females were found to be more resistant to irradiation. The irradiation effect on the mortality of male worms was statistically significant scarcely from the 61st day on. The long period of permanence of the sterile adult irradiated worms in the portal system of mice and their probable involvement in the development of immunoprotection (the so-called concomitant immunity, without the immunopathological involvements for the host) are here discussed. PMID- 2259830 TI - B and delta hepatitis virus infection in a population of west Africa. AB - Among the 424 serum samples examined, the prevalence of hepatitis virus infection turned out to be 89.6%, with 15.6% of HBsAg positivity. Some of the samples belonged to an afferent population and some other to workers of a West Africa rural hospital (Pop. Rep. of Benin). 27.3% of the positive subjects presented active replication of the virus, shown by the presence of HBcAg. Among the HBcAb positive subjects the anti-delta antibodies showed a positivity frequency of 19.7%. HBsAg presence in 15% of pregnant women suggested the importance of HBV mother-foetal transmission in the district. The examined results can be compared with those obtained in other African areas, with similar socio-economic conditions. PMID- 2259831 TI - [Fluorescent method (fluorescein diacetate and ethidium bromide) to study the viability of Cryptococcus neoformans in liquor]. AB - The utilization of the fluorescent method (fluorescein diacetate DF and ethidium bromide BE), to verify the viability of fungal cells, was studied in 40 samples of liquor, from patients with neurocryptococcosis. For removing leukocytes and red blood cells, which produce interfering fluorescence, good results were obtained with 0.3% saponin solution. After processing of liquor, 0.1 ml aliquots of resulting suspension were mixed to equal volumes of fresh DF-BE solution. The best incubation period for staining was 30 minutes, resulting in good differentiation between viable (green fluorescence) and non viable (red fluorescence) cells. PMID- 2259832 TI - [Acute toxoplasmosis: evaluation of a thin-layer immunoassay technic for detection of IgM antibodies, anti-Toxoplasma gondii]. AB - A solid phase method, thin-layer immunoassay (IgM-TIA) was standardized and evaluated for the immunodiagnosis of acute toxoplasmosis, through the detection of IgM antibodies to Toxoplasma gondii. A total of 300 serum samples from serologically defined acute toxoplasmosis and, from non-related infections, was investigated by IgM-TIA. Statistical analysis were carried out in comparison with conventional tests, the immunofluorescence test for the detection of IgM antibodies (IgM-IFI) and hemagglutination test which uses 2-mercaptoethanol serum treatment (2ME-HA). Also the correlation coefficients were calculated for various Toxoplasma gondii antigen concentrations, as well as, the influence of the antigenic concentration on the relative indices of sensitivity and specificity were verified. The intra and inter test reproducibilities were demonstrated statistically, as well as, the reutilization of T. gondii antigen was proven to be possible for at least 10 times. The data indicated that antigenic concentrations, from 70 to 100 Cmg/ml, were able to provide maximum sensitivity and specificity. IgM-TIA displayed similar diagnostic efficiency to those two conventional tests here utilized, and may be employed to make diagnosis of acute toxoplasmosis, mainly if laboratory animals are available. PMID- 2259833 TI - [Tinea favosa. Report of a familial occurrence in Itapecerica da Serra (municipality of Greater Sao Paulo)]. AB - Four cases of Tinea favosa occurred in the same family are reported in a small city of Brazil (Itapecerica da Serra--State of Sao Paulo). Trichophyton schoenleinii was isolated from all four cases. Treatment consisted of oral griseofulvin (10 mg/kg/day) for at least three months. PMID- 2259835 TI - Pulmonary cavities colonized by actinomycetes: report of six cases. AB - Six cases of a cavitary pulmonary ball formed by Actinomycetes are reported. They were observed in the state of Bahia, Brazil. All patients complained of cough and hemoptysis and the pathological study showed bronchiectasis and small cavities in the lungs. The lesions contained micro-colonies of Actinomyces, identified by morphology, staining properties and culture in two cases (thioglycolate media). In the six patients the disease was limited to the lungs. In one patient grains were found, within micro-abscesses in the surrounding parenchyma. Probably the invasion occurred due to ulceration of bronchial mucosa that was covered by granulation tissue. The author suggests that as in nocardiosis actinomycosis may have an invasive form, a saprophytic one may and colonize pulmonary cavities. PMID- 2259834 TI - [Bacterial flora of the oral cavity, fangs and venom of Bothrops jararaca: possible source of infection at the site of bite]. AB - Culture of fang, fang sheath and venom of fifteen healthy freshly captured Bothrops jararaca were analyzed. The bacteria most frequently encountered were group D streptococci (12 snakes), Enterobacter sp. (6), Providencia rettgeri (6), Providencia sp. (4), Escherichia coli (4), Morganella morganii (3) and Clostridium sp. (5). The bacteria observed are similar to those found in the abscesses from Bothrops bitten patients. Since these snake mouth bacteria may be inoculated during the snake bite, bacterial multiplication and infection may occur under favorable conditions. PMID- 2259836 TI - Vaccination of dogs against Leishmania (Viannia) braziliensis. PMID- 2259837 TI - Commercially available anti-S-100 protein serum stains M. leprae in leprosy tissues by immunohistochemical procedures. PMID- 2259838 TI - Early rheumatoid arthritis--onset, course, and outcome over 2 years. AB - Eighty-nine patients, 33 men and 56 women, with early definite rheumatoid arthritis were followed for 2 years. Two-thirds were seropositive. About 1/3 were eventually treated with second line drugs. The disease mostly had an insidious onset initially involving the finger joints. Early remission occurred in 16%. Patient relevant measures such as pain, patient's overall assessment of disease activity and anxiety decreased significantly. Disability evaluated by the HAQ disability index remained at a low level. The joint damage score (JDS) in hands and feet increased steadily and only 18% were nonerosive after 2 years. One-third developed hand deformities which was associated with higher JDS. A joint function index (SOFI) correlated significantly with JDS. Twenty-eight percent had a slower rate of joint damage progression the second year. There was no significant correlation between JDS and disease duration. Six patients developed rapidly progressive damage in larger joints, five in the hip joints and one in the shoulder joint, all requiring joint replacement. The ability to predict outcomes with clinical and laboratory variable obtained at entry was of limited clinical usefulness. By applying discriminant analyses 67%-80% of the cases who fared worst regarding clinical, functional, and radiological features could be correctly classified. PMID- 2259839 TI - Lymphocyte infiltration and the synthesis of IgM and IgA rheumatoid factors by rheumatoid synovial membrane. AB - IgM and IgA rheumatoid factor (RF) synthesis by synovial membrane mononuclear cells was measured in 14 patients with rheumatoid arthritis (RA). The results were compared with blood mononuclear cell cultures and correlated with the intensity of lymphocyte infiltration of the synovium. IgM RF was produced by all synovial cultures compared with 56% of blood cultures; IgA RF was produced by 86% of synovial cultures and by 21% of blood cultures. A correlation was observed between synovial IgM RF synthesis, but not IgA RF synthesis, and the intensity of T cell and B cell infiltration of the synovial membrane. PMID- 2259840 TI - The effect of gold treatment on monocyte interleukin-1 production in rheumatoid arthritis. A prospective study. AB - Monocyte interleukin-1 (IL-1) production in vitro was studied in 49 patients with rheumatoid arthritis (RA) and 31 controls. Twenty-six of the RA patients were studied prospectively for up to 12 months after beginning chrysotherapy. About half of the patients (group 1) exhibited pretreatment levels of monocyte IL-1 secretion (as measured by bioassay or B-IL-1) significantly higher than that of the controls. Immunoreactive IL-1 (IR-IL-1) levels, however, were similar to controls. Clinical improvement in this group of patients was modest and transient but could be associated with a fall in the level of IL-1 (B-IL-1 and IR-IL-1) secretion. Other RA patients (group 2) appeared to have normal or reduced pretreatment levels of IL-1 secretion. Chrysotherapy resulted in significant clinical improvement within 3 months, and this was associated with an increase in IL-1 (both B-IL-1 and IR-IL-1) secretion by the patients' blood monocytes to normal or supranormal levels. Thus these two groups of RA patients (which differed only in the average duration of disease) had different prognoses in relation to chrysotherapy and the effect of chrysotherapy-induced remission on monocyte IL-1 secretion was opposite. These results suggest that monocyte IL-1 production in vitro reflects changes secondary to the anti-rheumatic effects of chrysotherapy. PMID- 2259841 TI - Complement-mediated inhibition of immune precipitation in rheumatoid vasculitis. AB - Complement-mediated inhibition of immune precipitation (CMIP) was measured in patients with rheumatoid arthritis (RA), rheumatoid vasculitis (RA VASC), patients with skin vasculitis not associated with a systemic connective tissue disease and normal healthy controls. CMIP was impaired in 100% (14/14) of the RA vasculitic patients, 60% (12/20) of the RA patients and 22% (2/9) of the dermovasculitic patients. The degree of impairment of CMIP was significantly greater in the RA vasculitic patients compared to the non-vasculitic patients. This difference was due to the significantly lower complement levels and the presence of higher concentrations of an inhibitor of CMIP in the RA vasculitic sera. The levels of this inhibitory activity correlated significantly with IgM rheumatoid factor concentration. Serial studies in three patients with RA vasculitis treated with corticosteroids and immunosuppressive drugs showed significant clinical improvement in two patients, which was associated with improvement in CMIP, reduction in circulating immune complex levels and reduction in IgM rheumatoid factor concentrations. PMID- 2259842 TI - Methotrexate therapy in rheumatoid arthritis patients diminishes lectin-induced mononuclear cell proliferation. AB - Methotrexate (MTX) is an anti-folate drug used in cancer chemotherapy because of its anti-proliferative effects. However, it is unclear whether the anti proliferative effects of MTX contribute to the efficacy of low-dose MTX in the treatment of rheumatoid arthritis (RA). To date, either no change or a paradoxical increase in lectin-induced proliferation has been observed in cultures of peripheral blood mononuclear cells (PBMC) from MTX-treated RA patients (RA + MTX). In these earlier studies, high folate-containing media and tritiated thymidine (3H-TdR) were used. Our studies were designed to test the hypothesis that the use of a culture medium with a low folate content along with tritiated deoxyuridine (3H-UdR) permits detection of diminished phytohemagglutinin (PHA)-induced proliferative responses of PBMC from RA + MTX. The data demonstrate decreased PHA-induced cellular proliferation of cultured PBMC from RA + MTX compared with controls. When comparing the PBMC proliferative responses in high vs low folate medium, a significantly greater increase (P less than 0.05) in proliferation occurs in the cells from RA + MTX cultured in the high folate medium. This suggests that an in vivo folate-deficient state of the cells from RA + MTX may be corrected in vitro when a high folate medium is used in culture. We conclude that the use of 3H-UdR and a medium containing folate within the normal range of plasma folate levels eliminates artifacts associated with the use of high folate medium and 3H-TdR, which obscures the anti proliferative effect of MTX in RA patients. PMID- 2259845 TI - [Hypertrophic and/or obstructive primary cardiomyopathies: genetic, etiologic, physiopathologic aspects]. AB - The morphological features, mode of presentation and physiopathology of hypertrophic cardiomyopathy (HCM) are variable. Autosomal dominant seems to be the usual mode of transmission but with variable presentation. From the anatomical point of view, the hypertrophy is asymmetrical with septal predominance. The main histological features are myocytic architectural disorganisation, fibrosis and abnormal coronary arteries of small diameter. Ventricular hyperkinesis is usually present and sometimes associated with outflow obstruction, the physiological role and mechanisms of which are still not fully understood. On the other hand, abnormal diastolic function is frequently observed, and, quite independently of disease of the epicardial coronary arteries, ischaemic phenomena may occur. Although the biological substrate of HCM is unknown, abnormalities of the adrenergic system and transmembrane calcium flux probably play a part in the expression of the disease. PMID- 2259844 TI - [Cardiac transplantation: indications and results]. AB - Although many problems remain, cardiac transplantation is now associated with a 5 year survival rate of about 70 per cent which is a very acceptable therapeutic result in patients with cardiac failure and no other medical or surgical alternative. Parallel improvement in the medical management of chronic cardiac failure has prolonged survival of many patients. Transplantation should only be considered if the benefits not only in terms of survival but also in terms of quality of life, are greater than of survival but also in terms of quality of life, are greater than those of medical treatment of the cardiac disease. The indications and timing of cardiac transplantation are therefore based on a complex prognostic evaluation adapted to each individual case which may eventually need reconsideration. Satisfactory results depend on strict patient selection with respect for the surgical indications and contra-indications. PMID- 2259843 TI - HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients. AB - This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA. PMID- 2259846 TI - [Primary hypertrophic cardiomyopathies. Diagnosis and treatment]. AB - Hypertrophic cardiomyopathy (HCM) is currently considered to be a condition characterised by abnormal diastolic function, sometimes associated with left ventricular outflow obstruction which appears to be a secondary phenomenon. It is important to avoid overlooking this diagnosis especially in young subjects, because of the risk of sudden death, but conversely, false positive diagnosis can result in a serious social and psychological handicap. Echocardiography has assumed a major role in the diagnosis and follow-up of HCM over the last decade. It allows analysis of the localisation, extension and severity of the septal hypertrophy and of the mechanism of systolic anterior motion of the mitral valve. Cardiac doppler completes the non-invasive assessment of this condition by demonstrating the presence or absence of outflow tract obstruction, evaluating diastolic dysfunction, and documenting mitral and occasionally aortic valve regurgitation. Only severely symptomatic patients who do not respond to high dose medical therapy and for whom surgery might be an option need cardiac catheterization. Strenuous physical activity and sport are not recommended in asymptomatic forms. It is vital to identify those patients at high risk of sudden death (family history of sudden death, 48 to 72 hour Holter monitoring). In the absence of silent arrhythmias, preventive therapy should be more general in patients under 30 years of age. Despite a better understanding of the disease, the indications of medical and surgical treatment remain controversial and poorly defined. Treatment is mainly medical with Propranolol as the drug of choice. The dosage has to be tailored for each individual patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259848 TI - [Amiodarone: a general antiarrhythmic agent]. AB - Amiodarone, a molecule initially developed as an antianginal agent, is considered to be the most powerful antiarrhythmic drug. It prolongs ventricular repolarisation and the refractory periods of all cardiac fibres uniformly, and, at high doses, blocks the transmembrane sodium influx. Amiodarone exerts a non competitive alpha and beta adrenolytic effect and interferes with the metabolism of the thyroid hormones. Its accumulation is slow and excretion progressive. The main metabolite (desethylamiodarone) also has electrophysiological properties and contributes to the antiarrhythmic effect. The efficacy of amiodarone in cardiac arrhythmias is limited in chronic administration by the possibility of dose dependent secondary effects. PMID- 2259847 TI - [Surgical mitral valvuloplasty in the treatment of mitral valve diseases]. AB - Mitral valve repair surgery, in presence of a pure mitral leakage or one associated to a stenosis, is not only possible but has been well codified for a decade. According to damage, there are two methods of operation: valvular mobilization surgery and valvular motion amplitude reduction surgery. They are usually associated to annuloplasty with a Carpentier prosthetic ring. The incidence of late mortality is of 0.6 p. 100 pt/yr, that is to say 91.7 p. 100 at 13 years. This late survival rate is about 20 p. 100 better than for a valvular replacement. Reoperations rate is 1.6 p. 100 pt/yr. The incidence of thromboembolic event occurrence is low: 0.5 p. 100 pt/yr. The ideal indications for mitral valve repair are represented by damage of prolapse from a degenerative origin for which results are better and more constant. For rheumatic damage, the valvular repair indication depend on the valvular tissue elasticity and area. The presence of calcification and extensive fibrosis remain on principle counter indications. PMID- 2259849 TI - [Primary results of the MONICA project]. AB - The MONICA project is an international study coordinated by the WHO, designed to explain the important variations of coronary mortality observed in the industrialised countries over the last 20 years. Thirty-nine centres in 27 countries are participating in the project which, over a 10 year period will, in geographically determined zones; a) record the numbers of acute myocardial infarcts and coronary deaths, b) analyse the treatment of acute cardiac events, and c) evaluate the cardiovascular risk factors and preventive measures in the general population. The MONICA-France project comprises three registers (Bas Rhin, Haute-Garonne and the urban community of Lille), and a coordinating centre. The preliminary results confirm the wide geographic variability of coronary mortality with a prevalence slightly higher in Alsace and the North than in the South-West of France. The approximative frequency of coronary events in France is estimated at 112,000 infarcts and over 175,000 acute coronary episodes and deaths. Information is provided about the severity of the principal coronary risk factors and the conditions of their treatment in the register zones. A study of the accessibility of emergency treatment of acute infarction in the Bas-Rhin area, has demonstrated the key role of the general practitioner as the first contact but confirmed the long delay to hospital admission which nullified the potential benefits of thrombolysis in a high proportion of cases. However, the significant decrease in hospital mortality of acute infarction observed over a 3 year period in the three register zones, is probably related to the number of patients thrombolysed in that time. PMID- 2259850 TI - [Eye saccades]. PMID- 2259851 TI - [What is expected from the medical treatment of ulcer disease?]. PMID- 2259852 TI - [Is cesarean section too often done?]. PMID- 2259853 TI - [Resuscitation and the digestive system]. PMID- 2259854 TI - [Non-morphine analgesics]. PMID- 2259855 TI - [Right ventricular failure. Etiology, physiopathology, diagnosis, course and prognosis, treatment]. PMID- 2259856 TI - [Neurotic disorders in children]. PMID- 2259857 TI - [Hyperprolactinemia. Physiopathology, diagnosis and principles of treatment]. PMID- 2259858 TI - [Fractures of the upper humerus in adults. Etiology, diagnosis, principles of treatment]. PMID- 2259859 TI - Microbiology, chemotherapy and mortality of brain abscess in Newcastle-upon-Tyne between 1979 and 1988. AB - 71 patients admitted to Newcastle Regional Neurosurgical Centre between 1979 and 1988 with a diagnosis of brain abscess are reviewed. The overall mortality was 9.9%, with an operative mortality of 7%. The bacteriology of these abscesses is discussed in detail, together with the importance of effective standardized antimicrobial treatment regimens. The low mortality figures appeared to be in direct relationship to early recognition of this condition, prompt surgical intervention and effective chemotherapy. PMID- 2259860 TI - Hepatitis B infection in a non-drug abusing prostitute population in Mexico. AB - The prevalence and risk factors of hepatitis B infection were studied in 354 non drug abusing female prostitutes and 360 female controls in Tijuana, Mexico. Hepatitis B surface antigen (HBsAg) was found in the same percentage (0.8%) of prostitutes and controls. In contrast, antibody markers (anti-HBs or anti-HBc) were found in a significantly higher percentage of prostitutes than controls (8.2% vs. 2.2%, p = 0.0006). Prostitutes also had a higher prevalence of a positive RPR/FTA-ABS test for syphilis (p less than 0.0001). There was a significant association between the presence of hepatitis B markers and positive syphilis serology and a history of having had a STD. In this non-drug abusing population, prostitution was found to be a risk factor for total hepatitis B infection but not for surface antigenemia. Further studies are indicated to determine the incidence of chronic infection in adult women following sexual transmission of hepatitis B. PMID- 2259861 TI - Prevention of Pneumocystis carinii pneumonia relapse by aerosolised pentamidine, 60 mg biweekly, using an Acorn System 22 nebuliser. AB - The effectiveness of biweekly administration of 60 mg aerosolised pentamidine (AP) as secondary prophylaxis against relapse of Pneumocystis carinii pneumonia (PCP) was investigated in 45 male AIDS patients. The nebuliser used was an Acorn System 22. In total the patients received AP for a mean period of 13.8 months (3.4-28.8). Six episodes of recurrent PCP were recorded. Relapse per full year of treatment on AP was 12%. PMID- 2259862 TI - Rapid aetiological diagnosis of pneumonia based on routine laboratory features. AB - The values of some basic laboratory features on admission to hospital were recorded and compared in 418 adult patients with community-acquired pneumonia, namely erythrocyte sedimentation rate, C-reactive protein, white blood cell (WBC) count, serum lactate dehydrogenase (S-LD), serum alanine-aminotransferase, and serum sodium. Discriminant analysis was performed to obtain an aetiological diagnosis. WBC value of greater than 15 x 10(9)/l strongly indicated a bacterial and, especially a pneumococcal aetiology, whereas increased S-LD could imply a mycoplasmal infection. For patients less than 50 years of age the equation C2 = 1.788 + 0.204 x WBC-0.0909 X S-LD was constructed, in which C2 greater than 0 indicated a pneumococcal aetiology. This function correctly classified 31/33 (93.9%) patients with a mycoplasmal and 20/31 (64.5%) patients with a pneumococcal infection. Patients with viral, Haemophilus influenzae or chlamydial infection could not be discriminated from each other. The age of the patient, WBC and possibly S-LD on admission are easily accessible parameters and these results could therefore be of value in daily clinical practice in hospitals. PMID- 2259863 TI - Norfloxacin treatment of salmonellosis does not shorten the carrier stage. AB - In a prospective controlled study we evaluated the effect of early norfloxacin treatment on the duration of salmonella carriage after acute salmonellosis. The study was carried out during an outbreak of Salmonella typhimurium infection at a military base. 23 patients received norfloxacin 400 mg twice daily for 7 days while 29 patients served as untreated controls. A patient was considered to have ceased being a carrier on the date of the first of 3 negative consecutive cultures. Four weeks after diagnosis 30% of the treated patients and 31% in the control group were still carriers. The corresponding figures after 8 and 12 weeks were 17 and 3% and 4 and 0%, respectively. Thus, one week of norfloxacin treatment instituted at an early stage of salmonellosis did not shorten the duration of carriage. PMID- 2259864 TI - Antibody response to Staphylococcus saprophyticus in urinary tract infection. AB - The serological response towards Staphylococcus saprophyticus in young women with symptomatic urinary tract infection was measured with an enzyme-linked immunosorbent assay (ELISA) and a direct agglutination (DA) test. In both assays a marked antibody response was found in 2 of 3 patients with acute pyelonephritis caused by S. saprophyticus. Patients with acute cystitis due to S. saprophyticus or Escherichia coli showed antibody titers comparable to those of healthy controls. PMID- 2259865 TI - Increase of acute frontal sinusitis in southwestern Finland. AB - The number of patients hospitalized for acute infection in the frontal sinuses at the Department of Oto-Rhino-Laryngology of Turku University Hospital has increased markedly during the last decade. Causes for this increase were evaluated by comparing the backgrounds and medical findings of the 134 patients treated in the years 1977-81 and those of the 421 patients treated in the years 1982-86. Nasal polyps and history of allergic rhinitis were considerably more common in the latter patient group. The disease also seems to recur increasingly in the same patients. Of the aerobic bacteria Streptococcus pneumoniae and Haemophilus influenzae were the most common pathogens and the share of H. influenzae increased slightly, becoming the commonest pathogen in the latter 5 year period. Increasing air pollution in the city area of Turku is worth consideration and should be investigated further. PMID- 2259866 TI - Splenic abscesses: a review of 20 cases. AB - Splenic abscesses are rare. We present 20 new cases diagnosed in Denmark from 1982 to 1987. Five cases were diagnosed at autopsy. 10 were initially treated with splenectomy, 1 died. Five were treated with drainage and antibiotics resulting in 1 treatment failure who survived after splenectomy, and 1 death. The incidence of splenic abscesses in Denmark was 0.056% per 1,000 somatic hospital discharges per year or for the 5 cases discovered at autopsy 0.0049% per year of all hospital deaths. Splenic abscess should be suspected in the febrile patient with left upper quadrant tenderness and splenomegaly and the diagnosis confirmed by ultrasonography or computerized tomography. Treatment of choice is still splenectomy and antibiotics although favorable results have been achieved with drainage procedures in combination with antibiotics. PMID- 2259867 TI - Amikacin once daily: a new dosing regimen based on drug pharmacokinetics. AB - Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug. PMID- 2259868 TI - Fungemia with Saccharomycetaceae. Report of four cases and review of the literature. AB - Invasive fungal disease with Saccharomycetaceae is very rarely reported and these fungi are usually considered nonpathogenic. We report here 4 cases of positive blood cultures with fungal species belonging to this family. Severe neutropenia, permanent central venous catheter, ongoing antibacterial chemotherapy, and major abdominal surgery were identified as risk factors for fungemia in patients. In the immunocompromised host isolation of such species from sterile fluids cannot be ignored but should be considered an opportunistic infection and treated as such. PMID- 2259869 TI - Lethal disseminated adenovirus type 1 infection in a patient with chronic lymphocytic leukemia. AB - A 45-year-old woman with chronic lymphocytic leukemia developed fever followed by decreasing liver function. Her clinical condition rapidly deteriorated, acute liver necrosis developed, and the patient died of hepatic and renal failure. Adenovirus type 1 was isolated before death from blood, urine and throat and found in liver and lung at autopsy. Serologic studies showed that the infection was primary and that the patient was unable to mount an antibody response to the infection. Adenovirus type 1 is an uncommon cause of lethal infections in immunocompromised patients. PMID- 2259870 TI - Candidal pyarthrosis in an AIDS patient. AB - The unusual occurrence of a case of indolent Candida albicans pyarthrosis arising as a late complication in a 57-year-old male patient with AIDS, despite prior treatment with amphotericin B for candidemia, is reported. The case is discussed in the context of candidal pyarthrosis and of the rarely reported other fungal arthridites in AIDS patients. PMID- 2259871 TI - Salmonella infection in total hip replacement: tests to predict the outcome of antimicrobial therapy. AB - We report a hematogenous implant infection with Salmonella dublin in a renal transplant patient with total hip replacement. A 16-month treatment with cotrimoxazole failed, as evidenced by culture and electron microscopy, despite persisting low MIC after therapy. Data from a foreign body animal model and in vitro tests, which take into account the properties of adhering and stationary phase bacteria, explain the failure of a long-term treatment with cotrimoxazole. The patient was subsequently cured by ciprofloxacin which was successful in these tests. No relapse was noted after a follow-up of 1 year. PMID- 2259872 TI - Pivampicillin/pivmecillinam in the treatment of shigella carriers. AB - 24 patients (4-65 years old; median age 29 years) excreting shigella bacteria greater than 8 weeks were treated with the combination pivampicillin (0.25 g)/pivmecillinam (0.20 g), 2 tablets 3 times a day for 14 days. 23/24 patients (96%) were culture negative after treatment. The one patient that did not respond to treatment carried a strain with intermediate sensitivity to mecillinam and resistance to ampicillin. It is concluded that pivampicillin/pivmecillinam is effective for patients excreting shigella bacteria. PMID- 2259873 TI - Treatment of bacterial vaginosis in pregnancy with a lactate gel. AB - 10 pregnant women with bacterial vaginosis were treated vaginally with a low-pH lactate gel intermittently during 6 weeks. Reappearance of a lactobacillus dominated vaginal flora was observed after a few days treatment in all patients. All women experienced a subjective disappearance of abnormal vaginal discharge and malodour. This local treatment restores the normal vaginal acidity and facilitates recolonization with lactobacilli. It may be preferable to oral antimicrobial therapy, especially during pregnancy. PMID- 2259874 TI - Lyell's syndrome associated with rifampicin therapy of tuberculosis in an AIDS patient. PMID- 2259875 TI - Effect on urogenital flora of antibiotic therapy for urinary tract infection. PMID- 2259877 TI - Introduction: B27-associated diseases. AB - As an introduction, a hypothesis for the causation of ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and rheumatoid arthritis is outlined. It comprises ten basic mechanisms. With that hypothesis as a background, a further ten issues based on clinical evidence are presented for discussion. Finally, four questions are presented on behalf of the clinicians. PMID- 2259876 TI - Serum levels of beta 2-microglobulin in HLA-B27+ patients with acute anterior uveitis and ankylosing spondylitis. AB - Serum levels of beta 2m were monitored in 89 HLA-B27+ patients with acute anterior uveitis (AAU) and in their first degree relatives. Serum levels of both patients and relatives were not elevated compared to sex and age matched controls. Neither the activity of the uveitis, nor the presence or absence of ankylosing spondylitis (AS), correlated with beta 2m levels. On the contrary, 6 of 27 HLA-B27- patients with AAU had elevated serum levels of beta 2m. These findings do not confirm previous reports which showed elevated serum levels of beta 2m in patients with AS. A possible role for beta 2m in the pathogenesis of HLA-B27+ AAU and AS is discussed. PMID- 2259878 TI - Structure of class-I MHC molecules: HLA-B27 and disease. AB - In this introductory article, the structure and function of HLA class-I molecules is discussed. The differences between HLA-B27 and the other class-I molecules are described. It is suggested that HLA-B27 contributes to autoimmune phenomena, but little is known about the actual autoimmune mechanisms that cause the B27 associated disease. PMID- 2259879 TI - B27+ disease versus B27- disease. AB - When studying heterogeneity of B27-positive disease versus B27-negative disease, very different patterns of disease associations but also a lot of similarities may be observed. In general, B27-positive disease has an earlier onset, a more severe and prolonged clinical course and is more often complicated by acute anterior uveitis and peripheral arthritis, whereas B27-negative disease is accompanied by psoriasis, inflammatory bowel disease and erythema nodosum in a higher percentage of the cases. Despite these differences, B27-positive disease may be completely undistinguishable from B27-negative disease in a number of individual cases. Family aggregation and male preponderance, however, are only seen in B27-positive disease. These observations may lead to the conclusion that HLA-B27 is probably not the only key to the pathogenesis of these diseases, but nevertheless an important genetic factor in disease expression. PMID- 2259880 TI - Follow-up study of ankylosing spondylitis over a period of 12 years (1977-1989). AB - A follow-up study was performed on 256 patients with ankylosing spondylitis. HLA B27-negative Dutch patients very rarely had classical idiopathic ankylosing spondylitis. Most of these patients had psoriasis or inflammatory bowel disease or they were foreigners living in The Netherlands. Many of the B27-negative patients only have sacroiliitis. Psoriasis or inflammatory bowel disease among the HLA-B27-positive with a classical ankylosing spondylitis is rare. PMID- 2259881 TI - Genetical factors--other than HLA-B27--in "HLA-B27-associated diseases". AB - All studies among acute anterior uveitis (AAU) and ankylosing spondylitis (AS) agree on the importance of and high association with HLA-B27. However, the majority (greater than 95%) of the HLA-B27+ population will never develop such disease. There are two--generally accepted--important factors increasing the relative risk for developing AAU or AS. Firstly being HLA-B27 positive and secondly being a first degree relative of a patient with AAU or AS. The association with HLA-B27 is probably based on particular HLA-B27 properties, but not on a preferential association with one of the HLA-B27 subtypes. The subtypes are equally distributed among normal controls and AAU or AS patients. Family investigations among the relatives of AAU and AS patients predict the existence of other pathogenic factors in addition to HLA-B27. Strong though circumstantial evidence for a genetical origin of these factors was found in the families. It was also found in AAU and AS family investigations that associations with other polymorphic causal genes on chromosome 6 that are in linkage disequilibrium with HLA-B27 are highly improbable. PMID- 2259882 TI - Genetics of non-HLA marker genes in HLA-B27-positive and -negative ankylosing spondylitis families. AB - In families of HLA-B27+ ankylosing spondylitis (AS) patients, the occurrence of secondary cases of sacro-iliitis (SI) among B27+ first degree relatives is more than tenfold higher than expected from the population association of AS with HLA B27. Secondary cases of SI also occur in relatives of HLA-B27- AS patients. We addressed the question whether other genetic factors than HLA-B27 played a role in the familial occurrence of AS and SI in B27+ and B27- AS cases. To this we tested 24 genetic marker systems including GM and PI in first degree relatives of AS patients: 118 first degree relatives with 16 secondary SI cases in families of 23 B27+ AS probands and 74 relatives with 6 secondary SI cases in families of 14 B27- AS probands. With a LIPED analysis we found no significant evidence for linkage for any of the markers tested, including HLA. In a co-segregation analysis we found a significant deviation from random segregation for HLA-B27 (p = 0.0005) and for HLA haplotypes (p = 0.052) to affected B27+ AS/SI siblings. No such deviation was found to B27- AS/SI cases. For GM and PI we found no significant cosegregation with AS/SI in B27+ and B27- families. In conclusion, apart from HLA-B27, we found no significant effect of any of the genetic marker systems tested in explaining the familial clustering of AS and SI among B27+ and B27- AS patients. PMID- 2259883 TI - HLA-B27 is necessary but not sufficient. AB - It is discussed why some, but not all HLA-B27-positive persons get disease when triggered by certain infections. The conclusions are that a possible modifying gene may be found on the other HLA haplotype or outside the HLA complex. Given an epidemic infection afflicting a family, it is the possible differences of other environmental factors which may be of interest, not a further description of the infection initially recognized. The familial clustering of disease is based upon modifying genetic factor(s) and/or environmental factor(s) shared by the family members. Timing of the environmental factors may be instrumental. Penetrance of genetic predisposition may also depend on coincidence of randomly occurring environmental factors. PMID- 2259884 TI - Inflammation in HLA-B27-associated diseases. AB - The pathogenetic mechanisms in the development of spondyloarthropathies are multifactorial. These include the possible role of infective micro-organisms which can by direct invasion lead to persistence of microbial antigens and thus trigger arthritis or by cross-reactions with the host tissue lead to inflammatory symptoms or by cross-reactions with HLA-B27 trigger cytotoxic T-cell response. After the primary event, exaggerated inflammatory response can lead to amplification of inflammation. The components in the amplification of inflammation include hyperreactive neutrophils and serum factors such as enhanced production of activation products of complement in subjects with HLA-B27. The enhanced neutrophil function seems to persist in patients with previous severe inflammatory symptoms during acute reactive arthritis or in those with late inflammatory complications. The enhancement is probably caused by priming effect by lipopolysaccharide, which seems to persist for a long period in patients with acute reactive arthritis. Enhanced production of monokines can contribute to the enhanced inflammation in patients with spondyloarthropathies. The primed phagocytes can respond vigorously when rechallenged with antigenic load during a new infection, thus leading in some patients to recurrent or chronic inflammatory symptoms. Antimicrobial therapy or sulphasalazine by modifying antigen elimination or absorption can diminish inflammatory response during acute arthritis and in chronic spondyloarthropathies. Long-term follow-up studies are needed to find out whether prolonged therapies with these agents affect the prognosis of spondyloarthropathies. PMID- 2259885 TI - An increased prevalence of anti-Borrelia burgdorferi antibodies in ankylosing spondylitis: fact or artefact? PMID- 2259886 TI - HLA and Lyme disease. PMID- 2259887 TI - Theoretical models to explain the association of HLA-B27 with ankylosing spondylitis. AB - A critical examination of the five different models proposed to explain the "AS B27" problem, has demonstrated, that two of these, the two-gene theory and the plasmid theory are no longer considered to provide satisfactory explanations of the phenomena. The remaining three theories are molecular mimicry, chemotaxis hypothesis and the receptor theory. It is difficult at this stage to decide which of these three models provides the best solution to the "AS-B27" problem, but a majority of research workers favour the receptor theory. PMID- 2259888 TI - Biosynthesis and assembly of MHC antigens. PMID- 2259889 TI - Dysfunction of HLA-B27. AB - Every HLA antigen, as defined by the WHO-HLA Nomenclature, is unique. The major function of these molecules is to present antigen-peptides to the T-cell receptor, thereby contributing to the immunological defence mechanism. This function is regulated for each MHC antigen by its unique structure, with the peptide-binding pockets of the three-dimensional groove of the corresponding molecules playing the critical role. However, HLA-B27 is special by virtue of its disease association(s). Various aspects which might provide an explanation for- or at least a clue to an understanding of the specific role of--B27 in its disease associations are reviewed. Since it appears that there are no published experimental data which would support either of the alternative hypothetical possibilities, the bulk of current theories must therefore be purely speculative. The only lead to a better understanding of the function of B27 in disease associations is the postinfectious reactive arthritis. If it is the B27 molecule itself which is involved, further in vivo work on B27 transgenic animals might help solve this problem with its numerous unknown factors. PMID- 2259891 TI - Attempt to show inhibition by oxygen in the modifying factor assay. AB - An Australian laboratory has demonstrated that antibodies to certain strains of enteric bacteria react with cells from HLA-B27-positive patients with a 'modifying factor' (MF) from these bacteria. These observations have proved difficult to reproduce. We investigated the possibility that oxygen inhibits the test by blocking B27, but we were unable to obtain consistent positive results. PMID- 2259890 TI - Trial and error in producing ankylosing-spondylitis-selective antisera according to Andrew Geczy. AB - Geczy found that rabbit sera raised against Klebsiella strain K43 cross-reacted with the cells from HLA-B27 positive patients with ankylosing spondylitis (AS). Other laboratories failed to reproduce these results. After a series of unsuccessful attempts, however, we managed to prepare one selective antiserum, using E. coli, isolated from a Dutch Bechterew patient, in offspring of rabbits Geczy sent us. Ever since we obtained irreproducible results only. This paper reports about the many attempts we have made to produce a discriminating antiserum for use in a combined vital stain and dye-exclusion assay. PMID- 2259892 TI - Effect of H-2 genes on expression of HLA-B27 and Yersinia-induced arthritis. AB - HLA-B*2705 transgenic mice were continuously backcrossed to mice of the B10 background with various haplotypes. A high level of expression of the HLA-B27 protein was detected on peripheral blood lymphocytes (PBLs) from mice homozygous for H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes by FACS analysis with the ME-1 antibody. A lower level of expression of B27 was observed on PBLs from H-2v mice. Little or no expression of B27 was detected on PBLs from H-2 or H-2d mice. We hypothesize that the HLA-B27 heavy chain is analogous to and competes with endogenous class I heavy chains in the H-2d, H-2q and H-2v haplotypes. Interestingly, other studies in our laboratory have demonstrated that mice with the H-2d and H-2q haplotypes with deletions of certain T cell receptor subsets are more prone to Yersinia-induced arthritis (YIA). Therefore, the mouse model of YIA may provide insights into the mechanisms of HLA-B27-linked spondyloarthropathies in man. PMID- 2259893 TI - HLA class-I-transgenic mice as model system to study MHC-restricted antigen recognition in man. AB - In order to develop a possible animal model to study HLA linked diseases of man, we established HLA-B27 transgenic mice (TGM). As aberrant and overexpression of MHC molecules can be toxic for cells, we aimed at obtaining a physiological expression of the human antigen and used a genomic 25kb Sal I fragment for embryo injection, coding for the HLA-B* 2705 heavy chain. Five independent founder mice were obtained containing varying copies of the fragment (1 to 10). RNA analysis from different tissues showed an expression pattern similar to endogenous H-2 class I genes. HLA-B27 antigen could be detected on lymphocytes derived from all five founder mice, even in the absence of human beta 2-microglobulin (hu beta 2m). It was found that the presence of hu beta 2m strongly enhances HLA-B27 cell surface expression in mice with few copies of the transgene, but was not necessary for efficient and high cell surface presentation in the 10 copy line. In all HLA-B27 TGM lines, the HLA molecule functions as restriction element in anti-viral responses. In addition, we could show that T lymphocytes of the transgenic animals respond to the same HLA-B27 restricted influenza peptide as is recognized by human influenza-specific, HLA-B27 restricted cytotoxic T cell lines. PMID- 2259894 TI - B27-transgenic mice and disease. PMID- 2259895 TI - Value of anti-neutrophil cytoplasmic autoantibodies and other laboratory parameters in follow-up of vasculitis. AB - The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA), detected by indirect immunofluorescence, is of high sensitivity and specificity in the diagnosis of Wegener's granulomatosis and related diseases, associated with vasculitis. Titres of immunofluorescence are thought to closely reflect disease activity. In a retrospective series of 266 sera of 23 patients with at least one positive test for ANCA, disease activity was correlated with ANCA, assayed by immunofluorescence and by enzyme-linked immunosorbent assay; with rheumatoid factor and with erythrocyte sedimentation rate. All tests were of limited value in predicting disease activity or relapse. A normal sedimentation rate and, to a lesser extent, a negative result of ANCA-immunofluorescence, were useful in excluding active disease. PMID- 2259896 TI - A study of the effect of rheumatoid synovial fluid on proliferation and IL-2 production by total mononuclear cells and purified CD4+ cells of synovial fluid and peripheral blood. AB - T cells from synovial fluid (SF) of rheumatoid arthritis (RA) patients have previously been shown to proliferate less after mitogenic stimulation and produce less interleukin 2 (IL-2) than normal T cells. To test whether SF is responsible for the reduced T-cell responses, we studied the effect of inflammatory SF on peripheral blood (PB) RA and normal mononuclear cells (MNC) and CD4+ T cells and on RA SF MNC and CD4+ cells in vitro. Most rheumatoid SF present in concentrations of 50% and 5% during in vitro stimulation increased mitogen induced IL-2 production and proliferative response by normal PB and RA MNC and CD4+ cells. Other rheumatoid SF samples did not influence the T cell responses, while only a few samples had an inhibitory effect. The results indicate that SF contain both stimulatory and inhibitory factors and that the resultant effect on T cells may depend on the net effect of these. The results do not support the hypothesis that the apparently impaired function of SF T cells is due to contact with SF. PMID- 2259897 TI - A comparison of overall health between patients with rheumatoid arthritis and a population with and without rheumatoid arthritis. AB - Women with rheumatoid arthritis (RA) at a rheumatology outpatient clinic (PAT) were compared with women with RA in representative samples of the Gothenburg population (POP), and with non-arthritic women in this population (REF). Clinical routine measures disclosed substantial dysfunction in both RA groups. Their physical, psychosocial, and overall function, assessed by means of the Sickness Impact Profile (SIP), was more impaired than that of the REF. The PAT had a higher disease activity and worse overall health status than the POP. In definite and classical RA, a poorer SIP physical and overall function was noted in the PAT than in the POP group, despite similar mean age and mean disease duration. Women with probable RA in the POP group had worse SIP dysfunction than the REF, particularly regarding ambulation and personal care. The SIP was sensitive to variations in disease activity and comprehensively disclosed dysfunction better than routine clinical measures. PMID- 2259898 TI - OM-8980 and D-penicillamine in the treatment of rheumatoid arthritis. A 12-month double-blind randomized study. AB - Forty patients with active rheumatoid arthritis were included in this monocentre double-blind study comparing the therapeutic efficacy and safety of the immunomodulator OM-8980 with that of D-penicillamine. After 12 months of treatment, the parameters of Ritchie index, duration of morning stiffness, pain assessed by a visual analogue scale and categories, number of swollen joints, grip strength and erythrocyte sedimentation rate (ESR) were all significantly improved with OM-8980, as was the case for the Ritchie index, number of swollen joints and ESR with D-penicillamine. Significant intergroup differences were recorded for pain categories in favour of OM-8980 and for the Ritchie index and number of swollen joints in favour of D-penicillamine. The need for concomitant anti-inflammatory therapies and the assessment of efficacy by physicians and patients did not differ significantly between the two groups. OM-8980 was significantly better tolerated than D-penicillamine (5 patients with 5 side effects as compared with 12 patients with 16 side effects). OM-8980 can thus be regarded as an efficient and well-tolerated slow-acting drug for the treatment of rheumatoid arthritis. PMID- 2259899 TI - Resection arthroplasty of the shoulder. AB - Destruction of the gleno-humeral joint is a well-known and common feature of progressive rheumatoid arthritis. The most striking symptoms are pain and limited motion. Very occasionally spontaneous ankylosis occurs. The impact often relegates the patient to the second and third functional class according to the ARA classification system. The most commonly used surgical methods are endoprosthetic arthroplasty, double osteotomy and early and late synovectomy. Resection interpositioning arthroplasty (RIAP) of the rheumatic elbow joint using lyophilized dura mater has shown excellent results. This encouraged us to apply the same surgical principles to the shoulder joint in rheumatoid arthritis and this report presents the surgical procedure and the primary results of our first 13 patients. Very good results were achieved concerning immediate pain relief and mobility gain, while the muscle strength improved significantly after approximately one year. The surgical technique is fairly simple and postoperative exercises are preferably performed with the help of relatives. PMID- 2259900 TI - Ten-year follow-up of a patient with multicentric reticulohistiocytosis associated with myopathy. PMID- 2259901 TI - Disconfirmatory feedback in families of schizophrenics. AB - A new approach to the study of family communication and psychopathology, in particular schizophrenia, using Saugstad's theory about use of language as its point of departure is presented. Conflicts between family members were observed and measured using a new unrevealed difference technique, the Colour Conflict Method (CCM). Communication was analysed in terms of continuous feedback processes, using the new computerized method, Confirmation-Disconfirmation Coding System (CONDIS). Feedback mechanisms in the internal communication of families of schizophrenics, normals, and non-schizophrenic pathological controls (n = 21) are described. The findings show that families of schizophrenics lack the ability to adapt their communication to changing situational requirements. When conflicts were introduced, families of schizophrenics-in contrast to non-schizophrenics within the extended schizophrenia spectrum and normals-increased their frequency of disconfirmatory feedback reactions instead of expressing disagreements openly. This was due to active disqualifications occurring between the parents and from the parents towards their schizophrenic offspring, who reacted with incomprehensible egocentric communication acts. PMID- 2259902 TI - Dark adaptation of foveal cones during the cone-plateau period. AB - Following substantial bleaching by "white" light, absolute threshold, relative spectral sensitivity and sensation of hue of monochromatic lights were measured at the central fovea during the cone-plateau period. The absolute-threshold level was found to increase and then decrease markedly, the relative spectral sensitivity remained invariant, while the sensation of hues of monochromatic lights from the long- and middle-wave regions of the spectrum changed toward hues of shorter wavelengths. PMID- 2259903 TI - A commentary on Ronnberg's distinction between perception and cognition. AB - In a commentary on a note by Ronnberg (Ronnberg, J. On the distinction between perception and cognition. Scandinavian Journal of Psychology, 1990, 31, 154-156), it is argued that one of Ronnberg's criteria for theoretically distinguishing perception from cognition, that of different biological purposes, is invalid. Congruent with a broad definition of perception and cognition which most researchers agree upon, Ronnberg's two other criteria essentially state that how internally represented information is processed distinguishes between perception and cognition. However, the more strict criterion of whether explicit retrieval of information from memory is necessary is too dependent on a particular, rather limited theoretical framework. A third, less theory-dependent criterion of whether the information available in the stimulus is sufficient to account for comprehension may be useful in research which investigates hypotheses about similarities between perception and cognition. PMID- 2259904 TI - Mode distinctions in knowing: the view from perception. Comments on Ronnberg (1990) AB - Information available for perception has been shown to be specific, to have validity extending over time, and to be meaningful. Thus, cognition cannot be distinguished as that which exclusively provides adaptive coherence of action and reliance on constraints. Transitions between perception and memory/cognition, as two qualitatively distinct modes of knowing, must instead be expected to occur for purposes of ensuring optimal utilization of information relative to its temporal validity and usefulness. PMID- 2259905 TI - Facial reactions to auditory stimuli: sex differences. AB - This study explored whether males and females differ in facial muscle activity when exposed to tone stimuli with different intensity. Males and females were repeatedly exposed to 95 dB and 75 dB 1000 Hz tones while their facial electromyographic (EMG) activity from corrugator and zygomatic muscle regions were measured. Skin conductance responses were also measured. It was found that 95 dB but not 75 dB tones evoked increased corrugator activity. This effect differed significantly between males and females. Thus, it was only females that reacted with a significant increased corrugator response to the high intensity tone. While facial responses differed between the sexes, the skin conductance response patterns did not. Consistent with previous research it is concluded that females are more facially expressive than are males. PMID- 2259906 TI - [Transvaginal color Doppler for evaluating gynecologic pathology of the pelvis]. AB - Transvaginal colour Doppler Sonography was used to assess circulation in pelvic vessels in a group of 611 non-pregnant and 88 pregnant patients. A 5 MHz transvaginal probe was used to visualize the pelvic anatomy and blood flow. Further analysis was made by pulsed Doppler where flow velocity waveforms were recorded and analysed by calculation of resistance index (RI). In the normal flow pattern, the diastolic flow component was absent or small and the value of RI was greater than 0.50. In the abnormal flow pattern, the large diastolic flow component was evident and the value of RI was less than 0.50. The transvaginal colour Doppler assessment of tumour vascularity can be used for better non invasive characterisation of adnexal tumour and may be potentially useful as a screening test for ovarian malignancy. Because of its high sensitivity, specificity and accuracy, transvaginal colour Doppler Sonography is the imaging of choice, in diagnostic procedure of early pregnancy failure and ectopic pregnancy. The guidance of a pulsed Doppler beam by colour flow mapping helps to locate areas of the most abundant flow and makes examination more reproducible, faster and easier. PMID- 2259907 TI - [Diagnosis of malignant tumors of the uterus by transabdominal ultrasonography: a utopia?]. AB - Two hundred non-pregnant women with suspected uterine disease were included in a prospective study designed to assess the accuracy of sonography in conforming or excluding the presence of uterine cancer. All patients were operated on and the preoperative sonographic findings were compared with the final histological diagnosis. The predictive value of sonographic evidence of malignancy was 43.9% (18/41), the predictive value of benign disease was 94.8% (147/155). Sensitivity was 66.7% (18/27) and specificity 85% (147/173). The sonographic detection of uterine cancer is in need of improvement. At present it cannot be used as a substitute of invasive diagnostic tools in patients with suspected uterine cancer. PMID- 2259908 TI - [The value of gynecologic ultrasonography in comparison with gynecologic palpation]. AB - 210 patients were included in a prospective study comparing the respective advantages of pelvic sonography and bimanual gynaecological palpation. The diagnoses resulting from these two methods were confirmed in each case at the anatomic situs by laparotomy and also histologically. Each kind of examination was conducted independently by one of two different teams to exclude any mutual influence on the diagnosis. Under these conditions, 158 (75.2%) of the sonographic examinations and 144 (68.6%) of the gynaecological palpations resulted in a correct diagnosis. This difference was not significant. However, these data varied depending on pathological findings. In 165 patients, uterus pathology was diagnosed sonographically. This result was only slightly better than that of the gynaecological examinations. Sonography was significantly more accurate (p less than 0.01) only in determining the uterus length. However, sonography was clearly superior in the diagnosis of pelvic, in particular ovarian, tumours. In 45 patients with proven tumorous growth in this area, the sonographic diagnosis proved correct in 34 cases (75.6%), palpation however only in 22 cases (48.9%). This difference was highly significant (p less than 0.005). More precisely, significant differences were found in favor of sonography in: organ identification (p less than 0.001), organ demarcation (p less than 0.002), determination of internal structure (p less than 0.002), volume measurement (p less than 0.01), and--most important--indication of tumour type (p less than 0.01). PMID- 2259909 TI - [Gynecologic Doppler ultrasonography]. AB - The resistance of the vessel of the ovarian artery changes during the cycle. At the time of ovulation the resistance of the vessel of the ovarian artery decreases under the influence of steroid production in the ovary. The resistance decreases and the blood flow increases. In our study we could show that women with a normal cycle have low pulsatility indices in the ovarian arteries when oestradiol is rising. In women with PCO-Syndrome the blood flow in the ovarian artery is very low in spite of the fact that the patients got hormonal treatment. On the day of follicular puncture in our IVF-group and also on the day before, the pulsatility-index of the ovarian artery was very high in patients with PCO Syndrome and it was significantly lower in patients with normal cycle. The women with PCO-Syndrome had also low oestradiol levels in the plasma. In the group with PCO-Syndrome no woman became pregnant, women with high oestradiol levels and low PI of the ovarian artery at the time of follicular puncture became pregnant in 19%. PMID- 2259910 TI - [Differences in sonographic measurements of the fetal head and chest]. AB - Differences in measurements using cephalometry and thoracometry ante partum are reported. Two examiners performed fetal head and thorax measurements shortly after one another using the same ultrasonic equipment without knowing the measurements achieved by each other. A series of 195 measurements were made by a few less experienced examiners. The values measured showed a considerable scatter. The average difference between the biparietal head measurements was 2.23 mm, and the standard deviation of the differences of the values measured was 1.94 mm. In a further group of 175 fetuses the measurements were performed by two skilled examiners. For the diameter of the head there was an average measured difference of 1.38 mm and a standard deviation of the differences of 1.11 mm. For the average thorax diameter--corresponding to the arithmetical average from the straight and transverse diameter--the following results were achieved. 4.14 mm average difference of value measured an 3.41 mm standard deviation in the measuring run performed by less experienced ultrasonic examiners as opposed to 2.57 mm average difference and 1.74 mm standard deviation in the group of practised examiners. The average thorax diameter showed a considerably smaller scatter than the transverse thorax measurement on its own. The differences in the values measured could not be seen to be dependent on the gestational age. PMID- 2259911 TI - [Vaginal ultrasound study of the normal and incompetent cervix: attempting a mathematical assessment]. AB - A group of 217 pregnant patients was examined by vaginosonography. The group could be divided into 62 patients with incompetent cervix and 155 patients with normal findings. We measured the width of the internal os, the length and the thickness of cervix of all patients in intervals of 14 days. We registered a dynamic process pattern of cervical, morphological changes in the group with preterm delivery. We tried to reduce these cervical changes to an arithmetic formula. PMID- 2259912 TI - [Ultrasonography of cervical cysts and their differential diagnosis]. AB - Among 22 proven branchiogenic or thyreoglossal cysts, 15 presented with a characteristic pattern of homogeneous smooth reflections within a well-demarcated thin and elastic, deformable wall when using a high-resolution transducer. The other cases, showing an inhomogeneous texture and/or irregular walls, cannot be distinguished from inflammatory or neoplastic processes with central necrosis. Complete surgical removal is recommended especially in these latter cases. One case of malignant transformation was found. PMID- 2259913 TI - [Differential diagnosis of the low-echo thyroid gland]. AB - Hypothyrosis as a result of inflammatory disease of the thyroid gland, often is a diagnostic problem because of the insidious onset and its lack of specific symptoms. In the rather large amount of literature about sonography of the thyroid no papers with a systematic approach to this entity are found. In a prospective study we evaluated 36 proven cases and found a characteristic sonographic pattern of the thyroid with regard to its size, contour and structure. PMID- 2259914 TI - [Analysis of a method for Doppler study of the female breast]. AB - Besides characteristic morphological differences, carcinomas of the breast show remarkable changes of vascularity, which are essential for their enhanced metabolism. High-frequency CW Doppler allows to investigate normal and pathological vascularisation in the breast. In our basic study we examined 200 patients, 37 with breast malignancies (6 non-palpable lesions). 33 of the carcinomas showed pathological vascularisation. In an extended examination procedure we investigated also normal breast vascularisation and compared it with blood flow in lesions. We developed therefrom an easy and rational method which allows physiological blood flow measurements as well as a differentiation of breast lesions within a few minutes' time. PMID- 2259916 TI - [Ultrasonic diagnosis of fractures]. AB - For the first time, sonographic callus diagnosis concentrates not on the fracture gap but on the conversion process within the surrounding callus region to determine healing and reloadability of fractures. On evaluation of callus texture in relation to the adjacent muscle tissue a sensitive diagnostic parameter can be determined from B-scan images even in a clinical routine situation which is suitable for the monitoring of healing as well as determination of the fracture status. The results of a clinical study are presented and a parameter range is determined which can be used as a criterium for tibia fracture stability and reloadability. Principal agreement of parameter dependence on healing time is shown by fibula fracture diagnosis, too. PMID- 2259915 TI - [Comparison of the diagnostic value of the individual examination steps (triple diagnosis) in breast cysts]. AB - Basic examination (palpation and mammography) as well as triple diagnosis (sonography, aspiration cytology, pneumocystography) are employed in the diagnosis and therapy of mamma cysts. Among 133 aspirated cysts we found by sonography 6 complicated cysts; 4 of these were cyst wall carcinomas. We found one further complicated cyst by aspiration cytology with a PAP IV; therefore, this sonographically uncomplicated cyst was extirpated as well resulting in cystic mastopathy without any signs of malignancy. Sonography and pneumocystography agreed perfectly in the diagnosis of cysts. Additionally mammography revealed 3 occult carcinomas located beside uncomplicated cysts. Hence, in no case should mammography be omitted. Sonography is a reliable instrument in judging cysts; therefore, aspiration cytology or pneumocystography may be left out in special cases. PMID- 2259917 TI - High activity of daily-schedule mitoxantrone in newly diagnosed low-grade non Hodgkin's lymphomas: a 5-year follow-up. AB - Twenty-one consecutive previously untreated patients with low-grade non-Hodgkin's lymphoma were entered into a trial of mitoxantrone (5 mg/m2 daily for 3 days repeated every 3 weeks) between 1985 and 1986. After 8 to 11 cycles of treatment not exceeding a cumulative dose of 165 mg/m2, the patients were observed without further treatment. Seven patients had small lymphocytic lymphomas, 10 had follicular small cleaved cell lymphomas, and 4 had follicular mixed small- and large-cell lymphomas. As previously reported, both hematologic and nonhematologic toxicity was modest. Nine patients achieved complete remission (CR) and 12 partial remission (PR) (CR plus PR = 100%). In the subsequent 4- to 5-year observation phase, 1 patient withdrew from the study, 10 patients relapsed, and 10 remain in unmaintained remission (7 CR, 3 stable PR). Three relapsed patients have died of treatment-resistant disease. No long-term side effects have been observed. Follow-up studies of left ventricular ejection fraction using multiple gated acquisition scintigraphy showed no significant decrease in cardiac function. PMID- 2259918 TI - Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin's lymphoma. AB - Mitoxantrone (Novantrone, American Cyanamid Company; NO) and high-dose cytarabine (Ara-C; AC) have each been shown to be active in non-Hodgkin's lymphomas (NHL) in various studies. The studies reported here are sequential. The first study (NOAC I) combined high-dose cytarabine (3 g/m2/12 h as a 3 h infusion on day 1) with mitoxantrone (10 mg/m2/d on days 2 and 3). Of 31 patients with relapsed and refractory NHL, 7 achieved complete remission (CR) and 7, partial remission (PR). Myelosuppression was the major toxicity of this regimen. In the second study (NOAC II), the dosage of cytarabine was escalated to 3 g/m2/12 h on days 1 and 2 (4 doses) while mitoxantrone remained 10 mg/m2/d on days 2 and 3. The effects of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) were simultaneously studied. Twenty-three patients from five centers were treated with NOAC plus rhGM-CSF while 14 patients from four centers received NOAC II alone. A CR was achieved in 9 of 23 patients who received the additional rhGM-CSF and in 2 of 14 patients treated with NOAC alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nL) after chemotherapy was 8 days versus a median of 13 days without rhGM-CSF, while the duration of severe thrombocytopenia (less than 20/nL) was not significantly different. The rates of infection and mucositis were 25% and 17%, respectively, with rhGM-CSF compared to 53% and 60% without rhGM-CSF. Thus, this last nonrandomized pilot study indicates that administration of rhGM-CSF reduces the duration of chemotherapy-induced cytopenia and the rate of mucositis. This growth factor does not appear to result in stimulation of lymphoma cells. At present, a controlled randomized trial is being conducted using NOAC II with rhGM-CSF or placebo to establish the definitive role of this growth factor in the treatment of NHL. PMID- 2259919 TI - Treatment of low-grade non-Hodgkin's lymphoma by cytoreductive chemotherapy with prednimustine/mitoxantrone followed by interferon alpha-2b maintenance: results of a clinical phase II study. AB - In a clinical phase II study, the antitumor activity of the recently introduced combination of prednimustine and mitoxantrone (PmM) was evaluated in 17 patients with advanced low-grade non-Hodgkin's lymphoma after failure with or relapse after standard chemotherapy. The PmM regimen consisted of prednimustine 100 mg/m2/d orally on days 1 to 5, and mitoxantrone 8 mg/m2/d intravenously on days 1 and 2, giving a total dose of 16 mg/m2. Treatment was repeated every 4 to 6 weeks to a maximum of 6 cycles. Patients achieving complete remission (CR) or partial remission (PR) received two additional courses for consolidation, followed by interferon (IFN) alpha-2b 5 x 10(6) U subcutaneously three times a week until progression or relapse. Twelve of the 17 patients (71%) responded (CR, 4 and PR, 8). Side effects consisted mainly of neutropenia, which required dose reduction in 48% of treatment cycles. All 12 responders subsequently received IFN alpha-2b maintenance treatment. At present, remission duration ranges from 4.5+ to 17.5+ months (median 14.5 months). In comparison to unmaintained first remission prior to receiving PmM/IFN alpha-2b, a clear tendency towards a longer period of freedom from progression emerged in the 12 patients receiving IFN alpha-2b maintenance treatment during a second PR or CR. These data indicate a high antitumor activity of PmM in low-grade non-Hodgkin's lymphoma and suggest a beneficial effect of IFN alpha-2b maintenance. Present findings, however, will require confirmation in future investigations. PMID- 2259920 TI - Phase II study of lomustine, cytarabine, mitoxantrone, and prednisone (CAMP) combination chemotherapy for doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphoma. AB - A phase II study was conducted to evaluate the efficacy and toxicity of lomustine, cytarabine, mitoxantrone and prednisone (CAMP) chemotherapy in doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphomas (NHL). Among 30 patients, the complete remission rate was 27% (duration: 10, 16, 22, 35, 35+, 42+, 51+, 55+ months) and the partial remission rate was 20%. Median survival for complete responders was more than 4 years. The best responses were seen in patients with relapsed NHL compared to those with primary refractory NHL. Toxicity was mainly related to myelosuppression. The results suggest that the CAMP schedule can be applied on an outpatient basis with satisfactory efficacy in patients with relapsing intermediate- and high-grade malignant NHL. PMID- 2259921 TI - Recent trends in the management of lymphomas at M.D. Anderson Cancer Center. AB - The overall therapeutic strategy for the management of lymphomas at the M.D. Anderson Cancer Center consists of devising new drug combinations that are tested first in patients with relapsed lymphoma and, if successful, are then incorporated into first-line management. This article describes the preliminary results of the alternating triple therapy (ATT) first-line regimen for patients with M.D. Anderson stages B, C, and D of intermediate-grade lymphomas. This regimen is based on three non-cross-resistant combinations, two of which were originally developed as salvage therapy. Statistically significant improvement in the overall survival and failure-free survival at 1 year has already been seen for the stage D patients (high tumor burden and high lactate dehydrogenase levels). A new therapeutic strategy in current use for patients with Ann Arbor stages III and IV low-grade lymphoma is also described. This regimen consists of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone-bleomycin) alternating with ESHAP (etoposide, Solu-medrol [methylprednisolone, Upjohn Company], Ara-C [cytarabine], platinum) and NOPP (Novantrone [mitoxantrone, American Cyanamid Company], Oncovin [vincristine Eli Lilly and Company], procarbazine, prednisone). Maintenance interferon (IFN) is also used for 1 year. Finally, the current salvage regimen in use at the M.D. Anderson Cancer Center is described. This MINE-ESHAP regimen consists of an induction with mesna, ifosfamide, Novantrone (mitoxantrone), and etoposide, which is administered until maximum response and followed by consolidation with 3 to 6 courses of ESHAP. The preliminary results of this regimen are encouraging, but more follow-up is required before any conclusions can be drawn. PMID- 2259922 TI - NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease. AB - Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease. PMID- 2259923 TI - Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection. AB - Cachexia is a common problem in persons infected with the human immunodeficiency virus (HIV). Megestrol acetate, an agent used for the treatment of metastatic breast cancer, is associated with appetite stimulation and weight gain. To determine whether this drug might benefit HIV-positive patients, 22 such subjects (14 previously reported) were treated with oral megestrol acetate, beginning at a dose of 80 mg four times daily. All patients had lost at least 10% of their preillness weight prior to treatment; the median loss was 11.4 kg (range, 5.5 to 26.8). Preliminary data from patients observed during therapy from 2 to 72 weeks showed that 21 of the 22 patients gained weight; the average weight gain was 7.3 kg (range, -4.1 to 17.3). Three patients failed to gain weight on 320 mg per day of megestrol acetate; both appetite stimulation and weight gain were achieved with 460 mg per day in one and 640 mg per day in another. One patient continued to lose weight despite 480 mg per day megestrol acetate. The median time to peak weight during megestrol acetate treatment was 14 weeks. Seven patients returned to within 1 kg of their normal body weight. In three of the 22 patients treated, megestrol acetate and zidovudine were started simultaneously. For these three patients, weight gain was potentially due to the recognized weight gain associated with the initiation of zidovudine. For the remaining 18 patients, however, appetite stimulation and weight gain were a result of megestrol acetate. All patients tolerated the drug well. One patient developed a deep vein thrombosis. No patient developed peripheral edema or drug-related impotence. The appetite improvement and weight gain seen in this initial series are encouraging. The true effectiveness of megestrol acetate for HIV-related cachexia and the effects of treatment on quality of life are currently being assessed in a national prospective, randomized, double-blind, placebo-controlled trial. PMID- 2259924 TI - Current approach to the treatment of human immunodeficiency virus-associated weight loss: pathophysiologic considerations and emerging management strategies. AB - Relationships between nutrition and infection are generally complex, bidirectional, and not perfectly worked out. Healthy people can adapt to simple decreases in intake or increases in expenditure. However, the imposition of infection with associated cytokines may impair such adaptations, resulting in wasting of lean tissue. In human immunodeficiency virus (HIV) infection, nutritional abnormalities are common. Lean body mass depletion is associated temporally with death in a subset of acquired immune deficiency syndrome (AIDS) patients. Weakness, fatigue, and anorexia are important symptomatic complaints affecting quality of life. Pathophysiologic mechanisms remain speculative, although there is reason to suspect four theoretic factors: decreased intake, malabsorption, hypermetabolism, and altered metabolism. More than one disturbance may be necessary for clinical wasting to develop; ie, a primary abnormality plus a failure of homeostatic adaptation. Excess cytokine production also may be involved, but this is uncertain. Therapeutics remain empiric in the absence of known mechanisms. Current options are restricted to diet adjustments or supplements, treatment of underlying diseases (where possible), and rarely, parenteral alimentation. Promising investigational possibilities include an appetite stimulant (megestrol acetate) and therapies to oppose cytokine production or actions, but definitive beneficial effects on nutritional status, subjective performance, disease activity, or survival have not yet been demonstrated. Advances in clinical therapeutics await an improved understanding of pathophysiologic mechanisms and carefully designed clinical trials testing proposed interventions. PMID- 2259925 TI - Appetite stimulation and weight gain with megestrol acetate. AB - The extreme anorexia and cachexia associated with cancer and other disease states often have important physical and psychologic impact on both patients and their families. Weight gain resulting from megestrol acetate therapy in breast cancer patients suggests that progestins may be useful for alleviation of disease associated appetite and weight loss. Early breast cancer experience, as well as preliminary data from a randomized, placebo-controlled trial of high-dose megestrol acetate in cancer anorexia and wasting, is therefore reviewed. Although the precise mechanism by which megestrol acetate exerts its effect remains unclear, weight gain was observed in 75% of patients in the high-dose study and in nearly all of those who remained on therapy for 6 weeks. It was concluded that, although megestrol acetate cannot be expected to directly affect the prognosis of patients with hormone-insensitive tumors, it may increase host resistance by improving nutritional status and/or enhancing the quality of life. PMID- 2259926 TI - Front-line hormonal therapy for patients with advanced breast cancer: a community oncology research program. AB - Megestrol acetate was administered as first-line therapy to 152 patients with advanced breast cancer. Forty-three of 136 evaluable patients (32%) obtained an objective response (95% confidence interval, 24% to 40%). Toxicity was minimal, with only 4 patients requiring dose reduction. Megestrol acetate is an effective, well-tolerated agent in previously untreated patients with advanced breast cancer. PMID- 2259927 TI - Comparison of antiestrogen and progestogen therapy for initial treatment and consequences of their combination for second-line treatment of recurrent breast cancer. AB - A randomized clinical trial involving postmenopausal patients with estrogen receptor positive recurrent breast cancer is reported. Of 168 patients entered, 156 were evaluable, of whom 79 received oral tamoxifen citrate 10 mg twice daily and 77 oral megestrol acetate 40 mg four times a day. Partial response (PR) plus complete response (CR) rates (both arms, 34%) and time-to-disease progression were similar in both arms. Side effects and toxicity were minimal with both regimens, although more patients who received tamoxifen complained of hot flushes (33% v 11%) and more patients who received megestrol acetate had a 10% or greater weight gain at 6 months from baseline (51% v 19%). On progression of disease, 73 patients who had achieved a CR, PR, or stable response received the alternative hormonal treatment in addition to the original hormonal therapy. Ten of 40 patients (25%) who began treatment with megestrol acetate had a further CR or PR; none of 33 patients originally receiving tamoxifen had a response when megestrol acetate was added. Similarly, patients who received tamoxifen as an addition to their original megestrol acetate treatment also had a significantly longer time to second progression than did those in the comparative arm. It was concluded that as initial hormonal therapy for relapsed patients, either tamoxifen or megestrol acetate can be used with confidence. However, it is suggested that tamoxifen and megestrol acetate should not be used in combination, except for those few occasions when tamoxifen is added as second-line therapy following a completed megestrol acetate response, and the megestrol acetate is continued for its palliative effects on appetite and weight gain. Possible mechanisms behind these results are discussed. PMID- 2259929 TI - Therapeutic options in treatment of advanced carcinoma of the prostate. AB - Considerable controversy continues to surround the therapy of metastatic carcinoma of the prostate. Until recently orchiectomy and diethylstilbestrol (DES) were the only treatment options available. The development of megestrol acetate is of interest because of its broad spectrum of activity and excellent patient acceptability. Interim results of a study comparing megestrol acetate 120 mg/d plus mini-dose DES 0.1 mg/d with DES 3 mg/d are reported. Megestrol acetate had minimal side effects, with 2% of patients withdrawing from the megestrol acetate arm because of toxicity, compared with 37% from the DES arm. Significant cardiovascular toxicity occurred in 33% of patients taking DES and in 7% taking megestrol acetate. Both therapies achieved permanent suppression of serum testosterone to castrate levels. Time to progression and overall survival were longer with DES treatment, 17 versus 23 months and 24 versus 44 months, respectively, but this was not significant (P = .34 and P = .16, respectively). A review of the literature on the treatment of metastatic carcinoma of the prostate is presented to determine what should be recommended as standard therapy. Total androgen blockade is analyzed critically and results of therapy are compared with other modalities. Based on efficacy, cost, toxicity, and patient acceptability, orchiectomy still should be considered standard therapy and total androgen blockade should be considered experimental. PMID- 2259928 TI - Weight changes in women with metastatic breast cancer treated with megestrol acetate: a comparison of standard versus high-dose therapy. AB - One hundred seventy-two patients with advanced breast cancer were randomized to receive 160 or 800 mg megestrol acetate per day. Patients were monitored monthly for weight, blood pressure, performance status, edema, measurement of clinically evident lesions, and toxicities. Pretreatment characteristics were similar in both arms. Weight gain was the most commonly seen side effect, with 52% of patients gaining in excess of 10 lb and 28% gaining more than 20 lb. Median weight gain for standard-dose treatment was 5 lb compared with 18 lb for high dose treatment. There was no dose modification for excessive weight gain in any of the patients receiving the standard dose but doses were modified in 15% of those receiving high-dose megestrol acetate. Weight gains for both groups were analyzed at 30, 90, and 180 days after study entry. Treatment arm, age, prior therapy, response to prior endocrine therapy, race, performance status, dominant disease site, and number of disease sites were included in the analysis. At 30 days, patients taking high-dose megestrol acetate had a mean weight gain of 2.5 lb whereas patients taking the standard dose had stable weights. Factors predictive of weight gain were younger age (P = .0012) and fewer disease sites (P = .017). At 90 and 180 days, patients taking high-dose megestrol acetate had consistently gained more weight than those taking the standard dose (9.0 and 16.0 lb v 2.5 and 9.0 lb, respectively). Significant covariables were treatment arm (P = .0006) and younger age (P = .0211). Probability of gaining 20 lb was dependent only on treatment dose (P = .0002), and median time to a 20-lb weight gain was 217 days. Increases in systolic and diastolic blood pressures were seen in both groups, but the differences were not significant. Megestrol acetate is associated with weight gain in women with advanced breast cancer, and the amount of weight gained correlates directly with dose of megestrol acetate, length of treatment, and age of patient. PMID- 2259930 TI - Alleviation of cancer anorexia and cachexia: studies of the Mayo Clinic and the North Central Cancer Treatment Group. AB - Anorexia and cachexia are common clinical problems of many patients with advanced cancer. Approximately 20 years ago, a controlled, clinical study demonstrated that dexamethasone could stimulate appetites of patients with advanced gastrointestinal cancer without causing any apparent effect on patient weight or survival. More recently, two double-blind, placebo-controlled trials investigated cyproheptadine and megestrol acetate in patients with cancer anorexia/cachexia. The first of these studies suggested that cyproheptadine could mildly stimulate appetite without causing any discernible effect on patient weight. Megestrol acetate, on the other hand, can clearly cause an increase in patient-perceived appetite and food intake and can also lead to substantial nonfluid weight gain in a proportion of patients with cancer anorexia/cachexia. Ongoing studies have been designed to better study the appetite-enhancing effects of megestrol acetate. In addition, current studies are evaluating the effect of the drug hydrazine sulfate on the appetite and weight status of patients with advanced lung or colon cancer. PMID- 2259931 TI - A second look at tuberculosis mortality statistics. PMID- 2259932 TI - Hepatic granulomas. PMID- 2259933 TI - The hidden agenda. PMID- 2259934 TI - BOOP--bronchiolitis obliterans organizing pneumonia. PMID- 2259935 TI - An evaluation of 1987 tuberculosis deaths in Singapore. AB - Tuberculosis was responsible for 177 deaths in 1987. This study evaluated the accuracy of tuberculosis death certification by hospital doctors and general practitioners in 111 cases where hospital case-notes were available for verification. It revealed that only 49 cases (44%) died of active tuberculosis, 12 (11%) died of late effects of tuberculosis and 41 (37%) died of causes unrelated to tuberculosis. There was no evidence of tuberculosis in 9 cases. Only 39 cases (56%) of active tuberculosis certified by hospital doctors were correct compared to 10 (24%) certified by general practitioners. Hospital doctors certified 6 out of 9 deaths which had no evidence of tuberculosis. The actual tuberculosis mortality rate was estimated to be between 1.9 and 4.9 per 100,000 instead of the officially published 6.8 per 100,000 for 1987. PMID- 2259936 TI - Hepatic granulomas--an experience over the last 8 years. AB - Twenty cases of hepatic granulomas seen in the Department of Medicine over the period of 8 years from 1981-1988 were reviewed. Prolonged fever and jaundice were the commoner presentations. While the aetiology was varied, patients with tuberculosis and idiopathic causes formed the major groups. There were also 2 rare causes, one due to cytomegalovirus infection and the other a result of allopurinol hypersensitivity. The idiopathic group of cases fared well but those with tuberculosis did badly and 2 out of 6 died. The absence of pulmonary involvement and the high incidence of jaundice and liver dysfunction in the patients with tuberculosis were the other striking features. PMID- 2259937 TI - The hidden agenda and diagnosis in general practice. AB - Diagnosis in general practice involves more than the diagnosis of a physical illness. An important objective of a general practice consultation is to understand the hidden feelings and fears of the patients. Seven case reports are presented to demonstrate the need to go beyond the physical diagnosis and to identify the hidden agenda in order to make a comprehensive biopsychosocial diagnosis of the patient's problems. A good bedside manner is more than good manners. It is an essential ingredient of the diagnostic process in general practice. PMID- 2259938 TI - Screening for colorectal cancer in Singapore. AB - The incidence of colorectal cancer in Singapore has risen relentlessly since 1955. Today, the large bowel is the most frequent gastrointestinal cancer site among both men and women. Survival with this cancer has shown little improvement during this period. The prospects for further reduction in mortality through more radical surgery, adjuvant radiotherapy, chemo- or immunotherapy remain limited. Theoretically, detection of colorectal cancer at an earlier stage or detection of its precursors will reduce mortality. Screening for colorectal cancer is advocated to achieve this end. Success with screening programmes will depend on the diffusion of current knowledge about this disease to both health professionals and the general public. PMID- 2259939 TI - Parental influence in transsexualism. AB - This is a study of parental influence in a group of Chinese male and female transsexuals compared with a group of male and female heterosexual controls. There was no difference in the parental ages of the transsexuals and controls at time of their birth. The fathers of the male transsexuals and the mothers of female transsexuals were less involved in their upbringing. Using a bonding instrument, the fathers of male transsexuals were found to be less caring, and mothers of female transsexuals were less overprotective than the fathers and mothers of the controls. Studies on parental involvement in male transsexuals showed a weak father figure and an overinvolvement with the mother, and in female transsexuals, an unsatisfactory mother-daughter relationship. Abnormal parental child relationship, postulated as an important aetiological factor in transsexualism, needs to be further confirmed. PMID- 2259940 TI - Endobronchial tuberculosis--a report of 5 cases. AB - Endobronchial tuberculosis is not as well-known to internists as tuberculosis involving the lung parenchyma. Five cases with this condition are reported to illustrate the varied clinical manifestations. The presenting features of the 5 cases were lobar or lung collapse, unresolved pneumonia, dyspnoea and stridor. Bronchostenosis developed in 2 patients many years following chemotherapy, while stenosis of the trachea developed in one patient during chemotherapy. In another patient, the tuberculous granulation tissue simulated a lung cancer at bronchoscopy. Diagnosis can be difficult as endobronchial tuberculosis can occur in the absence of chest X-ray abnormality and sputum smear may also be negative for acid fast bacilli (AFB). Therefore, bronchoscopy should be done when the condition is suspected in a patient who has unexplained cough, wheezing, dyspnoea or haemoptysis. The modalities of treatment for fibrostenosis of a large airway include surgical resection followed by anastomosis, balloon dilatation, laser photoresection or a combination of both procedures. PMID- 2259941 TI - Group G streptococcal endocarditis and bacteraemia--a report of 3 cases. AB - Three patients with Group G Streptococcal infection presenting with endocarditis and septicaemia are reported. All had underlying cardiac disease, and one had diabetes mellitus and a colonic carcinoma. Our three patients responded to intravenous crystalline penicillin. PMID- 2259942 TI - Colonoscopy in children with bleeding per rectum. AB - There are few reports of colonoscopy in children. Twenty-six children with bleeding per rectum were examined colonoscopically to determine the aetiology of the bleeding. A total of 32 colonoscopies were performed. Except for 5 children who needed general anaesthesia, all the rest were performed with pethidine and diazepam sedation. The mean age of these 26 children was 63.5 months (SD 57.5 months, range 2 weeks to 180 months). Ten children had histologically confirmed colitis. Five had bleeding juvenile polyps and these were removed endoscopically. One had lymphoid hyperplasia and one had chronic solitary sigmoid ulcer. The rest were normal. It is concluded that colonoscopy can be performed safely in children and it is a good diagnostic and therapeutic procedure. PMID- 2259943 TI - Psychiatric morbidity in schizophrenic relatives--use of Self-Reporting Questionnaires (SRQ). AB - A validated study of the Self-Reporting Questionnaire (SRQ-20) of the World Health Organization against ICD-9 was found to have good validation indices at the cut-off point of 5/6. The sensitivity was 84.8% and specificity 83.7%. However, SRQ-24 had poor validation indices and are too sensitive to detect psychotic illness. Twenty-three per cent of 264 schizophrenic relatives who had been staying together with them and or actively involved in their care for at least one year had neurotic disorders compared with 1% who had latent schizophrenia. The prevalence of psychiatric morbidity was higher in the first degree relatives compared with non-first degree relatives. PMID- 2259944 TI - Margosa oil poisoning as a cause of toxic encephalopathy. AB - Margosa Oil is an extract of the seed of the Neem tree and is widely used as a traditional medicine by Indians in India, Sri Lanka, Burma, Thailand, Malaysia and Indonesia. Used mainly for external applications, it is often administered orally to neonates and infants regularly in small amounts. Margosa Oil causes toxic encephalopathy particularly in infants and young children. The usual features are vomiting, drowsiness, tachypnea and recurrent generalised seizures. Leucocytosis and metabolic acidosis are significant laboratory findings. Management is aimed primarily towards the control of convulsions although supportive management is equally important. Prognosis is usually good but fatalities and neurological deficits have been reported. We report here two infants with Margosa Oil poisoning presenting with encephalopathy. PMID- 2259945 TI - Sleep apnoea syndrome--a study of 5 cases. AB - Sleep apnoea syndrome (SAS) is common in the West but its prevalence is uncertain in Southeast Asia. Five Chinese patients seen in a Sleep Assessment Unit in Hong Kong are presented to illustrate the spectrum of clinical features and treatment methods involved in obstructive and central sleep apnoea. The first patient is a 45-year old woman with severe obstructive SAS and cardiopulmonary complications who improved significantly after tracheostomy. The second patient is a 43-year old man who improved with weight reduction and protriptyline. The third is a 42 year old man whose SAS did not improve with uvulopalatopharyngoplasty but with continuous positive airway pressure (CPAP). The fourth is a 12-year old girl with obstructive SAS who improved significantly after tonsillectomy. The last patient is a 52-year old man with central SAS who improved with CPAP. PMID- 2259946 TI - Botulinum toxin in the treatment of hemifacial spasm. AB - Thirteen patients with disabling idiopathic hemifacial spasm received botulinum toxin A injections to the affected muscles. Previous treatments, including one posterior fossa decompression, had no sustained benefit. There was excellent response in all the patients with improvement in social disability. Local side effects were mild and transient and include mild facial weakness. One patient had mild diplopia. The benefit lasted more than three months. Reinjection resulted in identical efficacy. Botulinum toxin A injection is a useful therapy for Hemifacial spasm. PMID- 2259947 TI - Refractive errors in Singapore medical students. AB - The refraction of 128 third-year medical students aged 20-22 was studied using a Topcon autorefractometer. The population was predominantly Chinese and comprised 44% females and 56% males. The mean refractive error was -3.75 D for males and 4.76D for females. In all, 82% of the students were myopic, 72% were found to have astigmatism. This study confirms clinical impressions that Singapore students have one of the highest prevalence rates of myopia and astigmatism in the world. PMID- 2259949 TI - Cutaneous manifestations of cardiac diseases. AB - Many general signs familiar to physicians can be found on the skin in cardiac patients. These include (a) cyanosis, central and peripheral, (b) erythremia, flushing and erythema, (c) digital clubbing and (d) alteration in texture. Specific cardiac conditions often have useful diagnostic cutaneous clues. Of these the association of coronary heart disease, hyperlipidemia and xanthomas is the most important. Rare syndromes such as the "leopard syndrome" often have distinctive skin signs. Multisystemic disorders may affect the heart and skin simultaneously or in sequence. They include collagen vascular diseases, amyloidosis, sarcoidosis and relapsing polychondritis. Finally iatrogenic disease arising from treatment of cardiac or cutaneous disease may induce changes in one or the other organ. The heart and the skin have much in common. These manifestations help elucidate the cause, evaluate the diagnosis, and follow the treatment and progress of these diseases. PMID- 2259948 TI - Early clinical manifestations of HIV infection. AB - HIV infection produces a spectrum of illness from totally asymptomatic infection to AIDS. In between these two extremes, infected persons may manifest a variety of signs and symptoms. These include an acute infectious mononucleosis-like illness, progressive generalised lymphadenopathy, and numerous cutaneous and oral lesions. Whilst most of these conditions are not pathognomonic for HIV infection, certain features may indicate the possibility of an underlying HIV infection. Clinicians should be aware of these tell-tale signs. PMID- 2259950 TI - Singapore--an ageing society. AB - Singapore is undergoing a rapid transition into an ageing society. This is due to a dramatic fall in the birth rate combining with a fall in infant and early childhood mortality rate as well as an improvement in the life expectancy. Other changes in the society such as the breaking up of the extended family structure, the changing role of women as well as the increasing expectations of elderly and their families are taking place at the same time. These changes will place increasing demands on the families of the elderly, social services, community and health services. There will have to be a rethinking on how we care for our elderly and the measuring required in meeting this challenge. PMID- 2259951 TI - Methodology in geriatric medicine. AB - Geriatric Medicine encompasses physical, mental and social problems in the elderly individual. To cater for varied changing needs a flexible system is required providing a range of services. A positive approach is advocated: without this, institutions will be overwhelmed by the flood of immobile, bedridden aged. Individualised care needs to be developed to ensure a good old age. PMID- 2259952 TI - Idiopathic bronchiolitis obliterans with organizing pneumonia in Singapore--first case report. AB - Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) has become accepted as a distinct disease entity. We report a patient who presented with the classical clinical, radiological and pathologic features of this uncommon condition. To our knowledge, this is first case to be reported in Singapore. This case also illustrates the difficulty of making a definitive diagnosis and emphasizes its therapeutic importance. PMID- 2259953 TI - Progressive hemifacial atrophy--a report of 2 cases. AB - Idiopathic hemifacial atrophy (Parry-Romberg Syndrome) is characterised by progressive wasting or loss of subcutaneous tissue in half of the face, starting usually in childhood, and often associated with skin changes. Two adult onset cases are described. They did not demonstrate skin changes but one had complicated hemiplegic migraine with headaches always ipsilateral to the facial wasting. PMID- 2259954 TI - Galactocoele of childhood--a case report. AB - A 31-month old boy with unilateral breast enlargement was found at surgical exploration to have a milk cyst whose lining epithelium was denuded in patches with chronic inflammatory cellular infiltration. The presence of foreign-body giant cells suggests involution of the secretory epithelium due to pressure effects of repeated trauma from attempted expression of the cyst contents. PMID- 2259955 TI - Colonic and breast carcinomas--association or metastases? Report of a case. AB - There is an increased incidence of colonic carcinoma in patients with breast carcinoma but colonic involvement secondary to breast carcinoma can also occur. The differentiation of the organ or origin (breast vs colon) of the abdominal tumour can be difficult and may benefit from the use of immunohistochemical staining with monoclonal antibodies that react preferentially with colon cancer (JGT) and breast cancer (3E1.2, BC2,BC3). Measurement of Mammary Serum Antigen (MSA) level as detected by the anti-breast monoclonal antibody (3E1.2) was also useful in the classification of tumours of uncertain origin. PMID- 2259956 TI - Occupational asthma due to spot-welding. AB - A case of occupational asthma from fumes due to spot-welding is described. The hazards from resistance welding have been considered minimal as compared to other types of welding. This paper illustrates the possible hazards of occupational asthma among welders including those doing spot-welding. It also illustrates the difficulties encountered in identifying the specific causative agent in such cases. PMID- 2259957 TI - Non-market economies in health. Introduction. AB - This paper introduces analyses of the state of health and of the health-care system in four Eastern European countries. The analyses focus on the issue of inequality in countries which share many characteristics including non-market economies, rapid urbanization and industrialization, and health systems which formally aim to provide equal access and treatment to all citizens. The measurement of social inequality in a non-market economy dominated by the state economy cannot be based on traditional class divisions; nor is income a good indicator of class position, salaries for professional and non-manual workers being lower than the average. Major relevant variables for which data are available are occupation, educational level and area of residence. Despite many system similarities the countries differ sharply in the level of resources devoted to health care and in health status based on mortality rates. PMID- 2259958 TI - The Bulgarian country profile: the dynamics of some inequalities in health. AB - The Bulgarian health-care system was based on the concept of equal access and treatment. In its early stages health improved and disparities between urban and rural areas and districts diminished. New problems, institutional rigidities and policy reversals led later to the concentration of health resources in the towns and cities and to a deterioration in rural health. Sharp disparities in reported health status exist between occupational, educational and income groups. Life expectancy has fallen. Some health problems arise from urbanization, industrialization and heavy internal migration. Others clearly derive from dysfunction in the health system itself, its narrow concept of health, the inability of health plans to adapt to changing problems and needs and the emergence of privilege in access and quality of care. PMID- 2259959 TI - The Hungarian country profile: inequalities in health and health care in Hungary. AB - Analysis of occupational, educational, urban/rural and regional data over several decades demonstrate large disparities in the availability of health care and in infant and adult mortality. Life expectancy increased in the immediate post-war period but in the late sixties improvement ceased and life expectancy at age 40 began to fall. Mortality has been particularly high for middle-aged males. Analysis by cause of death suggests the persistence of older poverty-type diseases co-existing with the newer lifestyle diseases. Reasons for system dysfunctioning are discussed--lack of health resources, rigid institutional structures, lack of integrated health policies, failure to adjust the distribution of resources to changing needs etc. The analysis raises the question of how to achieve a balance between equity and efficiency. PMID- 2259960 TI - The Polish country profile: economic crisis and inequalities in health. AB - Class position based on educational level is strongly associated with health status in Poland. Whilst infant mortality continues to fall, life expectancy at age 45 is lower particularly for males. Cause of death analysis shows a steady but slow fall in poverty-type diseases and a big increase in deaths from circulatory diseases and malignant neoplasms. Multiple regression analyses suggest that the main causal factors in inequality result from economic failure, differences in living conditions and lifestyles rather than from the evident inefficiencies in the health-care system itself. But there are significant inequalities in access to health care and especially to quality care. PMID- 2259961 TI - The Soviet country profile: health of the U.S.S.R. population in the 70s and 80s- an approach to a comprehensive analysis. AB - This paper reviews data from 1970 onwards on the distribution of health resources and health status for urban and rural areas and for the 15 Soviet republics. Major disparities exist between republics and especially between the European republics in the North and West and those of Central Asia and Transcaucasia. The former show relatively low infant death rates but high adult mortality, particularly for middle-aged males; rates of death due to circulatory diseases and malignant neoplasms have increased in these republics and special studies reveal a high incidence of alcohol-related diseases. In contrast, the Central Asian and Transcaucasian republics have extremely high infant mortality but high levels of life-expectancy thereafter. An index of medical inequality shows a much lower level of resources in these republics. Recent long-term strategies are described which aim to raise the income and status of health personnel from their relatively low levels and to equalize the distribution of health care across the country. PMID- 2259962 TI - International comparative analysis: main findings and conclusions. AB - This paper compares the experience of health and inequality reviewed in the Bulgarian, Hungarian, Polish and Soviet profiles. With health systems very similar in formal organization and stated aims, health status based on death rates has followed very similar tendencies in each country. Sharp post-war falls in infant death slowed down from the 60s onwards, but continued to fall. Life expectancy also increased but again from the late 60s began to fall, particularly for middle-aged men. Inequalities in health-care provision and access have been paralleled by inequalities in health outcome between areas and socio-economic groups. Comparative analysis, however, suggests that the dysfunctions of the health system have only been contributing factors to more fundamental causes stemming from socio-economic conditions, cultural and collective behaviour and the priorities of the political and economic system. Written before the transforming political events of late 1989, the reviews emphasise the need for change and a search for more effective and equitable systems and policies. PMID- 2259963 TI - Scientific racism: reflections on peer review, science and ideology. AB - The scholars who use Social Science & Medicine in their research and teaching, who publish their work in it, participate in its peer review of manuscripts, and attend its conferences belong to various nationalities, disciplines, and cultural traditions. Our common enterprise originated in and depends upon liberal democratic social institutions, and assumes their values. With all our differences and disagreements, we are committed to scientific research in a common effort to improve human health and welfare. Our professional careers are a large part of our personal lives, so that our science, our lives, and our values are a single fabric. The present lecture is a meditation on this situation based upon my own heritage, personal experience, and career in anthropology, and on the recent publication in Social Science & Medicine of an essay that attributed the epidemiology of AIDS to racial variation. PMID- 2259964 TI - The holistic heresy: strategies of ideological challenge in the medical profession. AB - Heresy is a neglected term in sociology. Yet insofar as science and the professions demand a conformity to basic concepts of ideology and practice, certain types of dissent may best be described as heresy. In this paper, heretical movements are discussed, and heresy is defined [8. Zito G. V. Social. Anal. 44, 123-130, 1983] as an attempt to challenge an orthodoxy for the right to control a discourse. The difficult position of the heretic as a challenger to an entrenched orthodoxy is described, particularly the attempt of heretics to assert their allegiance to the discourse itself while the orthodoxy attempts to portray them as traitors or apostates. It is argued that a four part strategy is necessary for a successful heretical challenge: the heretic must portray the discourse as in crisis, must provide an alternative ideology to rescue the discourse, must legitimize their ideology through appeal to a reframed historical myth, and must portray the orthodoxy as a betrayer of the discourse. The holistic movement in medicine is used as an exemplar to show how holistic physicians use this four part strategy. PMID- 2259966 TI - The near-death experience as status passage. AB - Near-death experiences are identity transitions with many of the major social features of status passage as these were originally formulated by Glaser and Strauss (Status Passage, Routledge & Kegan Paul, London 1971). These features are described and then compared with the similar experience of being a castaway after shipwreck. In this way, the clinical near-death experience can be analysed as one of a number of social near-death experiences. Viewed as status passage many of the psychological reactions can be usefully seen as context dependent processes rather than simply defence mechanisms or products of neurophysiology. PMID- 2259967 TI - A comparative study of feelings, attitudes and behaviors of patients with fibromyalgia and rheumatoid arthritis. AB - The purpose of this explorative study was to administer a battery of questionnaires related to a broad number of psychosocial factors in patients with fibromyalgia syndrome (FS). By doing this, psychological factors associated with the consequences of chronic pain in patients with FS could be identified and studied in more depth. Thirty-one patients with FS were compared to 30 patients with rheumatoid arthritis (RA) with regard to feelings about self, pain/ache preoccupation, support from significant others, psychosomatic symptoms, activities of daily living, job satisfaction, and future expectations. The results of the study showed that patients with FS had significantly more negative feelings toward themselves, were more preoccupied with thinking about their pain/ache, received more practical help from significant others, experienced more limitations with regard to activities of daily living, and experienced more negative feelings about employment than patients with RA. Patients with FS were also more pessimistic about future employment than RA patients. PMID- 2259965 TI - The measurement of health-related quality of life: major dimensions identified by factor analysis. AB - The measurement of quality of life is becoming more important in the evaluation of medical technologies and pharmaceuticals. Particularly when the several available therapies have similar effects on survival, quality of life measures may help decide which should be the therapy of choice. The Recovery Study utilized a multidisciplinary array of indicators of health-related quality of life and recovery. This paper reports factor analyses of 58 outcome measures on a study group of 469 persons who had undergone coronary artery bypass or cardiac valve surgery 6-months previously. The factor analyses revealed 5 orthogonal dimensions. We have named them: low morale, symptoms of illness, neuropsychological function, interpersonal relationships, and economic employment. The data argue that health-related quality of life is a multidimensional construct, and that these dimensions can be measured quantitatively with relatively simple interview and questionnaire approaches. The next research step is to determine whether the five dimensions of post-operative quality of life have different pre-operative predictors, and whether intervention on these predictors can improve the recovery and rehabilitation process. PMID- 2259968 TI - Scoliosis Research Society 24th annual meeting. Amsterdam, Holland, September 17 22, 1989. Proceedings. PMID- 2259969 TI - Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. AB - Stagnara wake-up tests, blood flow measures, somatosensory evoked potentials (SEPs), and neurogenic-motor evoked potentials (NMEPs) were elicited from 20 hogs before and after spinal cord overdistraction at L3-L4. Overdistraction was maintained from 5 to 30 minutes after loss of NMEPs. Results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia. Blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally. Finally, NMEPs were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than SEPs. NMEPs should provide the surgeon with more time for initiation of intervention techniques than SEPs. Because NMEPs and SEPs provide information regarding different spinal cord tracts, the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery. PMID- 2259970 TI - Relationship among level of distraction, evoked potentials, spinal cord ischemia and integrity, and clinical status in animals. AB - Somatosensory evoked potentials (SEPs) and neurogenic-motor evoked potentials (NMEPs) were recorded after overdistraction of the spinal cord at T5-T6, T12-L1, or L3-L4. Measures of spinal cord perfusion and clinical status were also administered. Results indicated that stiffer spinal segments allowed less distraction than more flexible segments. SEPs and NMEPs were lost quickly after overdistraction in stiff segments and slowly in more flexible segments. However, SEPs were less sensitive than NMEPs to effects from overdistraction. Spinal cord perfusion and integrity were consistent with reduced perfusion and structural damage after overdistraction in stiff segments; extremely reduced perfusion but no structural changes in more flexible segments. The application of these results to the clinical situation was provided. PMID- 2259971 TI - Urologic function after experimental cauda equina compression. Cystometrograms versus cortical-evoked potentials. AB - Twenty female beagle dogs underwent an L6-7 laminectomy and six dogs each had 25, 50 or 75% constriction of the cauda equina and 2 control dogs had laminectomy only. Cystometrograms were performed pre- and post-operatively and three months after constriction. Cortical evoked potentials were monitored pre- and post operatively and monthly for three months. After three months of constriction, the cauda equina of these dogs in each group was examined histologically and vascular circulation was examined by latex and India ink injection (Spalteholz technique). The control dogs had normal CMGs and CEPs. Twenty-five percent constriction caused no CMG changes and mild CEP changes. Fifty percent constriction caused no statistically significant CMG changes, major CEP changes and venous congestion of the nerve roots and dorsal root ganglia. Seventy-five percent constriction produced severe CMG changes with detrusor areflexia, increased bladder capacity and clinical incontinence. CEPs also had marked deterioration. Vascular analysis revealed severe arterial narrowing at the level of constriction and venous congestion of the nerve roots and dorsal root ganglia. Blockage of axoplasmic flow and nerve root atrophy was seen in all dogs with 75% constriction. Cortical evoked potentials were the most sensitive predictor of neural compression. CMGs were not sensitive until severe compression was achieved. Bladder dysfunction, i.e., detrusor areflexia, appears to occur with blockage of axoplasmic flow and early sensory changes occur with neurovenous congestion. PMID- 2259972 TI - Microcomputer reconstruction for analysis of spinal deformity and lung volume in hypokyphotic scoliosis. AB - Current techniques for imaging chest deformity are limited to two-dimensional representations, and clinical testing for lung volume measurements are based on pulmonary function studies that are effort-dependent. The authors evaluated spine deformity and lung volume by using a new three-dimensional microcomputer imaging technique. Results from preoperative and postoperative chest computed tomograms underwent boundary detection by expert human observers. Data were then processed by polygon surface tiling to create three-dimensional color images of the spine and lungs for display. This computer technique allowed: 1) visualization of the anatomic relationships from any angle, 2) assessment of spinal deformity in relation to lung volume, and 3) measurement of individual lung volumes. Three dimensional microcomputer imaging is a useful technique in objectively measuring lung volume and assessing postoperative changes. PMID- 2259973 TI - Cobb angle versus spinous process angle in adolescent idiopathic scoliosis. The relationship of the anterior and posterior deformities. AB - The standard clinical measurement for adolescent idiopathic scoliosis is the Cobb angle, measured from the end-plates of the end vertebral bodies in a standing radiograph. This measurement of anterior column structures describes the anterior spinal deformity. The posterior spinal deformity can be described by the "spinous process angle," measured from a curve joining the tips of the spinous processes. A computer model, and a radiographic study of Cobb angle, spinous process angle and vertebral rotation show that adolescent idiopathic scoliosis results in larger angulations of the anterior elements than posterior elements. This helps to explain some of the inherent limitations of posterior instrumentation, including Cotrel-Dubousset instrumentation, and of noninvasive posterior surface measurement systems. PMID- 2259974 TI - Digital radiography can reduce scoliosis x-ray exposure. AB - Digital radiology is a new computerized system of acquiring x-rays in a digital (electronic) format. It possesses a greatly expanded dose response curve that allows a very broad range of x-ray dose to produce a diagnostic image. Potential advantages include significantly reduced radiation exposure without loss of image quality, acquisition of images of constant density irrespective of under or over exposure, and reduced repeat rates for unsatisfactory films. The authors prospectively studied 30 adolescents with scoliosis who had both conventional (full dose) and digital (full, one-half, or one-third dose) x-rays. They found digital made AP and lateral image with all anatomic areas clearly depicted at full and one-half dose. Digital laterals were better at full dose and equal to conventional at one-half dose. Cobb angles were easily measured on all one-third dose AP and on 8 of 10 one-third dose digital laterals. Digital clearly depicted the Risser sign at one-half and one-third dose and the repeat rate was nil in this study, indicating digital compensates well for exposure errors. The study indicates that digital does allow radiation dose to be reduced by at least one half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x-ray exposure. PMID- 2259975 TI - Results of treatment of idiopathic scoliosis with the Charleston bending orthosis. AB - The authors present a preliminary retrospective review of the treatment of 32 patients with idiopathic scoliosis with the Charleston bending thoracolumbosacral orthosis (TLSO), a new, low-profile spinal orthosis. At the onset of treatment, the patients' mean age was 12.5 years and the mean Risser stage was 0.4. Females achieved menarche at an mean of 1.8 months after starting orthotic treatment. Single structural curves were treated in all patients. At this time, 2 patients have failed treatment, their curves progressing 12 degrees and 8 degrees, respectively. An additional 11 patients have successfully completed treatment, having reached skeletal maturity with no more than 5 degrees of curve progression. Their mean curve change was a 2.2 degrees decrease. The other 19 patients remain under treatment. The Charleston bending TLSO is worn only during nighttime sleeping hours. It is well tolerated, with excellent patient compliance and low psychological stress, and it may be as successful at curve control as other orthoses. Experience with more patients and longer follow-up is needed. PMID- 2259976 TI - Surface electrical stimulation versus brace in treatment of idiopathic scoliosis. AB - Surface electrical stimulation using the ScoliTron device was applied to 40 adolescent patients for treatment of idiopathic scoliosis. Adequate follow-up was available for 30 of these patients. The overall failure rate was 15 of 30 or 50%. Due to curve progression while using the ScoliTron, these patients either went on to a fusion (9 of 15) or were changed to a brace (6 of 15). The remaining 15 patients were considered successes with no curve progression (10 of 30 or 33%) or successful/failures with slight curve progression not requiring a change in treatment (5 of 30 or 17%). None of the various parameters analyzed were found to be useful indicators of successful treatment using the ScoliTron device. Electrical stimulation was found to be ineffective in preventing curve progression for idiopathic scoliosis. PMID- 2259977 TI - Internal forces and moments in transpedicular spine instrumentation. The effect of pedicle screw angle and transfixation--the 4R-4bar linkage concept. AB - The three-dimensional components of force and moment within the plates and screws of a bilevel transpedicular spine implant construct subjected to different physiological loads were determined by experimental and finite element methods. The effect of pedicle screw angle and transfixation were studied. Untransfixed 0 degrees pedicle-to-pedicle (P-P) angle constructs with limited screw-bone torsional resistance are unstable 4R-4bar linkages. They will not resist lateral load or (when not in a rectangular position) axial load until the spinal column load shares. Untransfixed constructs with (0 degrees less than P-P angle less than 60 degrees) are structures. However, as P-P angle approaches 0 degrees, the structure becomes more flexible (unstable) and some internal force and moment components exponentially increase (starting at approximately a 30 degrees P-P angle). Transfixation eliminated the linkage instability and associated exponential increase in internal loads. These observations apply to all bilevel systems that allow no relative joint motion between pedicle screw and longitudinal member. If relative motion does exist, other types of linkage instability can occur. PMID- 2259978 TI - Influence of bone mineral density on the fixation of thoracolumbar implants. A comparative study of transpedicular screws, laminar hooks, and spinous process wires. AB - Posteriorly directed load to failure testing of four different types of spinal implants was performed in individual T5 to S1 vertebra harvested from seven fresh frozen human cadaveric spines. The implants tested were: 1) Drummond spinous process wires, 2) Harrington laminar hooks, 3) Cotrel-Dubousset transpedicular screws, and 4) Steffee VSP transpedicular screws. The ultimate failure of each implant was compared with the bone mineral density of each vertebra to determine which implants, if any, were particularly advantageous in osteoporotic vertebrae. Before biomechanical testing, the spines were analyzed in vitro by dual photon absorptiometry to determine the bone mineral densities (gm/cm2) of each vertebra. The mean tensile loads to failure for each of the implants tested were as follows: Cotrel-Dubousset transpedicular screws: 345 Newtons; spinous process wire/button: 382 Newtons; Steffee transpedicular screws: 430 Newtons; and laminar hooks: 646 Newtons. The difference between the loads to failure for laminar hooks and the other implants was significant (P less than 0.05) using one-way analysis of variance. The overall correlation coefficient for bone mineral density with ultimate load to failure was 0.30 (P less than 0.001). The correlation coefficients were 0.47 (P less than 0.001) for spinous process wires alone; 0.096 (not significant) for laminar hooks alone; 0.37 (P less than 0.001) for Cotrel Dubousset pedicle screws; and 0.48 (P less than 0.001) for Steffee pedicle screws. Of the four different implants tested, laminar hooks were most resistant to failure from posteriorly directed forces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2259979 TI - Effect of spinal construct stiffness on early fusion mass incorporation. Experimental study. AB - The relationship between initial spinal construct stiffness and the stiffness of the resulting fusion mass was studied by performing standardized 10-segment posterior spinal fusions in goats. Animals were divided into 5 groups based on type of spinal construct, using rods of different diameters (3.2 mm, 4.8 mm, 6.4 mm) with or without rigid crosslinking to produce constructs of different stiffnesses. Stiffness data on 28 animals were obtained by removing the spines en bloc, at 6 or 12 weeks postoperatively, and performing load-deformation testing in axial and torsional loading to determine the stiffness of the fusion masses (rods removed). The initial construct stiffnesses were also compared by ex vivo testing on spine specimens to correlate initial construct stiffness with eventual fusion mass stiffness. In axial testing, results showed stiffer fusion masses from larger diameter rod constructs compared with smaller rod constructs. This was similar to results of control testing on spine specimens ex vivo. Rigid crosslinking did not produce stiffer fusions in axial testing, due to a technical limitation of the button-wire implants used to segmentally fix the rods at each vertebra. In torsional testing, stiffer fusion masses resulted from using larger rods, and rigid Crosslinking also produced the stiffest fusion masses, which was consistent with ex vivo testing. In general, larger diameter (stiffer) rods produced stiffer fusion masses, and no evidence of stress shielding was found. PMID- 2259980 TI - The use of fibrin sealant to reduce blood loss during Cotrel-Dubousset instrumentation for idiopathic scoliosis. AB - The increased complexity of Cotrel-Dubousset instrumentation has, as an unexpected side effect, a potential increase in blood loss. A prospective randomized study was undertaken to test the hypothesis that application of a fibrin sealant to exposed cancellous bone can significantly reduce blood loss during Cotrel-Dubousset instrumentation for idiopathic scoliosis. A significant difference was demonstrated in total body loss, loss per level fused, and loss per kilogram of body weight when comparing the sealant group with random controls. A significant difference was demonstrated in loss per level fused when comparing the sealant control with a historical control group. Thirty-three patients were randomly assigned to the fibrin sealant or nonsealant groups; another 10 patients operated on before planning the study were included as historical controls. The sealant was used to control bleeding at the bone graft donor site and in the spine after decortication. All patients underwent Cotrel Dubousset instrumentation for idiopathic scoliosis. There were no significant differences between groups with respect to degree of curvature, number of levels fused, age or weight of patient, or operating time. Total blood loss in the sealant group averaged 672 ml compared with 894 ml in the sealant control group. No patient in the sealant group required homologous blood. Given the increasing awareness of the complications of blood transfusion, the authors conclude that fibrin sealant is a useful adjunct to spinal surgical technique. PMID- 2259981 TI - Fusion levels and hook patterns in thoracic scoliosis with Cotrel-Dubousset instrumentation. AB - This study reports the results of treatment of adolescents with King Types 2, 3, and 4 idiopathic curves using Cotrel-Dubousset instrumentation. Imbalance was seen in Types 2 and 4 curves when distraction direction hook patterns crossing the thoracolumbar junction were employed. Imbalance was not seen when a modified hook pattern employing compressing forces across the thoracolumbar junction was employed. No imbalance was observed in Type 3 curves using the basic right thoracic curve hook pattern. In Type 4 curves, a second modified hook pattern is required to obtain improved correction and balance. The mechanism of production of imbalance is explained by a three dimensional analysis of the deformity and of the forces generated by the Cotrel-Dubousset system. PMID- 2259982 TI - Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel Dubousset instrumentation. AB - One hundred sixty patients with idiopathic scoliosis underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine. The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible. When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appears to provide the most physiologic sagittal contour. Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis. PMID- 2259983 TI - Decompensation after Cotrel-Dubousset instrumentation of idiopathic scoliosis. AB - Spinal decompensation after corrective surgery for scoliosis appears to be a significant problem after Cotrel-Dubousset instrumentation (CDI). CDI produces torsional changes in the instrumented and uninstrumented spine that could result in spinal imbalance. Preoperative and postoperative three-dimensional analysis including computed tomography (CT) scans to measure vertebral rotation and segmental rotation were performed to evaluate the importance of torsional changes. Moe/King Type II deformities had a substantially greater risk of imbalance. Deformities instrumented over fewer spinal segments were less likely to decompensate. Specifically, instrumentation excluding the mobile transition segment, determined by maximum segmental rotation and segmental Cobb angle, was likely to decompensate. Derotation and deformity correction excessive in relation to preoperative side bending flexibility and segmental rotation frequently resulted in imbalance. Spinal imbalance after CDI can be reduced by avoiding overcorrection and inclusion of mobile transition segments. PMID- 2259984 TI - Immediate complications of Cotrel-Dubousset instrumentation to the sacro-pelvis. A clinical and biomechanical study. AB - The authors reviewed the early complications in all patients fused to the sacro pelvis using Cotrel-Dubousset instrumentation at the Texas Scottish Rite Hospital. Sixteen patients were studied with an average follow-up of 13 months. Three methods of sacro-pelvis fixation were evaluated: iliosacral screws, sacral screws, and a technique whereby the caudle ends of the Cotrel-Dubousset rods were fashioned and inserted into the posterior iliac crest using the Galveston technique. Seven of the 16 sets of sacral screws (44%) failed during and after surgery. Two of the 7 sets of iliosacral screws failed postoperatively (28%). No failures occurred in the 8 sets of Cotrel-Dubousset rods placed with the Galveston technique. Seven of the nine medical complications observed (77%) occurred in the sacral screw group. Using calf spines, a biomechanical evaluation of each system was undertaken to determine strength of fixation. Each system was failed in flexion 3 times. The sacral screws were the weakest, pulling directly out of the sacrum at 40 N-M. Cotrel-Dubousset rods inserted with the Galveston technique were the strongest, experiencing rod deformities before flexion failure at 70 N-M. Iliosacral screws were of intermediate strength failing by rotation on the axis of the screws or pulling directly out of the ilium at 55 N-M. The authors conclude that using Cotrel-Dubousset rods inserted with the Galveston techniques was the strongest and safest method of sacro-pelvis fixation of the three tested. PMID- 2259985 TI - Surgical treatment of scoliosis in a spinal muscular atrophy population. AB - Seventy-eight patients were diagnosed with spinal muscular atrophy between 1969 and 1988. Scoliosis developed in 34 of these patients, an incidence of 60%. Thirty-one patients could be retrospectively reviewed by chart review or interview. The average follow-up was 11.5 years. Onset of scoliosis averaged 8.8 years. Twenty-two patients were treated nonsurgically and nine surgically. Patients had improved sitting balance and endurance after surgery. Complications of surgery included loss of correction in one patient, one pseudarthrosis, and one patient who required prolonged ventilatory support. The prolonged survival of patients with spinal muscular atrophy justifies aggressive orthopaedic management of scoliosis to prevent progression of deformity and improve sitting comfort. PMID- 2259986 TI - Combined anterior and posterior fusion for spinal deformity in myelomeningocele. AB - Since 1973, 50 of 54 children have been treated by the author with a combined anterior and posterior fusion. Twenty males and 34 females, ranging in age from 1 to 16 years, have been followed for a mean period of 5.5 years. Sixteen patients with a kyphosis averaging 113 degrees (range, 77 to 170 degrees) had correction of deformity to a mean of 35 degrees. Thirty-seven patients with a scoliosis averaging 73 degrees (range, 20 to 135 degrees) had correction to an average of 34 degrees (range, 0 to 75 degrees). There were 4 cases of deep wound infection successfully treated with drainage and antibiotics and only one case required implant removal after fusion/maturation. A pseudarthrosis was noted by radiograph in 6 patients, 3 of whom had isolated asymptomatic lumbosacral pseudarthroses. Three patients had pseudarthrosis at the thoracolumbar junction. These required repair and were successfully treated by supplemental posterior fusion resulting in an overall pseudarthrosis rate of 5.7%. Anterior fusion of the dysraphic spine allows greater correction of both spinal deformity and pelvic obliquity in addition to contributing significant strength to the fusion mass. Segmental spinal instrumentation with sublaminar and pedicular wiring to custom-contoured Luque rods provides excellent correction and immediate postoperative stability. PMID- 2259987 TI - Delayed anterior decompression in patients with spinal cord and cauda equina injuries of the thoracolumbar spine. AB - Forty-nine patients with complete and incomplete injuries of the spinal cord or cauda equina who had undergone anterior decompression at a minimum of 3 months after injury were examined. Follow-up was from 12 months to 19 years. Postoperative neurologic improvement occurred in 46.5% of patients with incomplete injuries. If the surgery was performed less than 2 years after injury, neurologic improvement occurred in 68% with an improvement in Frankel grade of 32%. Bladder function improved in 27% of patients and if operated on less than 2 years after injury improvement occurred in 43%. Conus medullaris decompression resulted in a 50% improvement. There was an 83% improvement in the pattern of pain after decompression. Of 23 patients with preoperative spasticity, 10 improved but 6 were worse after surgery. PMID- 2259988 TI - Sagittal index in management of thoracolumbar burst fractures. AB - In an effort to quantify the risk for late progression in burst fractures, the sagittal index (SI) was defined to help to assess the segmental deformity at the level of the fracture. The SI is a measurement of the kyphotic segmental deformity corrected for the normal sagittal contour at the level of the deformed segment. A prospective study was devised in 1986 for burst fracture treatment. Complete data were available on 35 patients (22 males, 13 females), with an average follow-up of 27 months. SI was greater than 15 degrees in the first group, the members of which were treated surgically. The technique is described. SI was less than 15 degrees in the third group, the members of which were treated conservatively. The second control group included patients with SI greater than 15 degrees but who were not treated according to the authors protocol for independent reasons. The results suggest that SI is a useful criteria to assess deformity and predict progression of segmental kyphosis. PMID- 2259989 TI - Blood flow direction in the lumbar nerve root. AB - The effect of clipping on lumbar nerve root blood flow rates in the region of the nerve root canal was studied experimentally in the hog. Blood flow rate was measured using the hydrogen washout technique. When the entrance zone was clipped with a microvascular clip, blood flow rate of the nerve root was decreased by 37% in comparison with the initial control rate; clipping at the exit zone reduced blood flow rate by 69%. Blood flow direction in the lumbar nerve root within the nerve root canal was found to be predominantly proximal. The current data indicate that the more lateral the impingement of the nerve root occurs, the more ischemic changes are induced. PMID- 2259990 TI - Quantification of leakage pressures after durotomy repairs in the canine. AB - This study was undertaken to investigate the relative strengths of dural repair using standard suture techniques, suture supplemented with tissue adhesive, and tissue adhesive alone. Uniform 2 mm dural defects were created in adult beagles, repaired, and then subjected to pressurization testing. Defects repaired with suture alone initially leaked within the range of physiologic pressurization, while those supplemented with tissue adhesive or repaired with tissue adhesive alone failed at higher pressurization levels. Histologic sections obtained from the dura treated with fibrin adhesive sealant demonstrated minimal inflammatory response not significantly different than those sections examined at sites repaired by suture alone. A new substance, fibrin adhesive sealant, appears to be useful in effecting dural repair due to its ability to withstand pressures greater than those obtained with suture alone. PMID- 2259991 TI - Facet loads in the canine lumbar spine before and after disc alteration. AB - The effect of externally applied spinal loads on facet mechanics before and after facet capsulectomy and disc alteration was investigated. Four control and four chymopapain-treated specimens were tested. Facet load and resultant load location were determined in the unaltered state, after facet capsulectomy, and after discectomy using a newly developed, noninvasive measurement technique. Resultant contact load locations shifted in a predictable manner. Caudal shift in contact locations occurred with chymopapain treatment or discectomy but was variable with capsulectomy. Facet load changed with applied load magnitude and direction; no significant change was noted after intradiscal chymopapain, discectomy, or capsulectomy. The significance of the lack of force change with disc narrowing is unknown. Perhaps, observed facet degeneration results from a change in the joint motion and contact location rather than change in facet load. PMID- 2259992 TI - Factors affecting fusion rate in adult spondylolisthesis. AB - The authors examined factors affecting fusion rate in the surgical treatment of 89 consecutive adult patients with spondylolisthesis. Two factors significantly improved fusion rate: combined anterior and posterior fusion and rigid postoperative immobilization in the cast. In 65 patients with isthmic spondylolisthesis, the fusion rate was raised from 70% when posterior fusion alone was used to 88% when combined anterior and posterior fusion was used. In 20 patients with degenerative spondylolisthesis, frequent use of combined anterior and posterior fusion contributed to a high overall fusion rate of 95%. Among patients with isthmic spondylolisthesis, postoperative cast immobilization resulted in a higher fusion rate of 90% compared with a fusion rate of 63% obtained after brace immobilization. PMID- 2259993 TI - Diurnal changes in straight leg raising. PMID- 2259994 TI - Technique for syringopleural shunting for the treatment of syringomyelia. PMID- 2259995 TI - [3 years of the National Institute of Public Health]. PMID- 2259996 TI - [Strategies to reduce morbidity and mortality caused by acute diarrhea in Latin America]. AB - Following the World Health Organization guidelines, the Latin American Diarrheal Disease Control Programs have directed its efforts towards the promotion of Oral Hydration Therapy (OHT) and appropriate dietary management during the diarrheal episode and convalescent period, aimed at diminishing the mortality secondary to diarrhea. In developing countries, OHT is preventing, annually, one million of childhood deaths due to dehydration. Yet, only one fourth of the total population of children suffering diarrhea are being treated with this therapy. Among the strategies to decrease diarrhea morbidity, breast-feeding and hand washing are top priorities. The fundamental strategy has been to promote educational programs to train health personnel and community members. To continue these actions, we suggested the creation of more secondary and tertiary level hospitals and the installation of community units of OHT. They should become self-sufficient and self-manageable and include other programs of primary health care, such as immunization, growth and development surveillance, family planning and pregnancy control. PMID- 2259997 TI - [Postneonatal mortality caused by diarrhea: a case-control study]. AB - A matched case-control study was undertaken in Naucalpan de Juarez, Estado de Mexico. The goal of this study was to identify the risk factors for diarrheal disease in children between seven days and one year of age. We identified 63 case and 188 controls. The most important risk factors were: mother's age greater than 36 years with an odds ratis (OR) 3.7, lack of breastfeeding (OR 11.3), breast and bottle feeding (OR 5.4), lack of intradomiciliary sewage (OR 8.3), repeated episoded of disease (OR 8.6) and father's consumption alcoholic beverages (OR 3.6). The main possible paths by which these factors influence mortality are discussed. Specific interventions for some of the factors are proposed. PMID- 2259998 TI - [Hepatitis B at a hemodialysis unit: description of an outbreak and control measures]. AB - An outbreak of hepatitis B virus infection in a hemodialysis unit which occurred after the arrival of an antigen carrier is described. During a period of five months, four cases were registered for an incidence of 14.8 percent, compared to 3.2 and 0 percent during preepidemic and postepidemic periods, respectively. There is no national surveillance program for hepatitis B in hemodialysis units in Mexico. We therefore suppose that there is a high frequency of infection among both patients and personnel, causing considerable morbidity, mortality and financial impact. The following article details the established control measures, and emphasizes the importance of implementing a permanent program which includes serological screening, policies for disinfection of machines, dialyzers, and environmental surfaces inside the unit, as well as general precautions for blood and other body fluids. The efficacy of the vaccine in patients and personnel is also discussed. PMID- 2259999 TI - [The role of induced abortion in changing fertility in Latin America]. AB - The data and estimates presented suggest that the incidence of induced abortion in Latin America is high. In individual countries the average total abortion rate, ie lifetime induced abortions, seems to be between one and two per woman of fertile age, if not higher. The incidence of induced abortion in Latin America appears to be among the highest in the world, comparable to several East Asian and East European countries. Apparently the practice of induced abortion was already quite extensive in urban Latin America in the 1960s at a time when the use of contraception was low. As of the 1980s, induced abortion accounts for about one quarter of deliberate fertility control, and contraception for the remaining three quarters. The high incidence of induced abortion is due to an imbalance between the strong motivation for smaller families and the imperfect availability and utilization of contraception. The motivation for smaller families is widespread and contraceptive prevalence has been increasing steadily since the 1960s, yet many barriers exist to its universal and effective application. Contraceptives are not always available when needed; frequently access is difficult, particularly for young, single, and poor women and men; knowledge about reproductive functions and contraceptives is deficient and erroneous among large proportions of women; and at times the use of contraception is at odds with deeply in grained cultural and social patterns, as well as with personal sentiments. For these and other reasons, contraceptive failure is not uncommon. Consequently, the incidence of unwanted pregnancy is high and many women/couples resort to induced abortion. PMID- 2260000 TI - [Risk indicators for the problematic consumption of drugs among young students. Applications in research and primary care at school]. AB - This article analyzes 33 risk indicators about problematic drugs use, based in epidemiological studies in representative student samples, carried out in Mexico since 1975. The indicators are distributed among the variation sources proposed by the classic epidemiological model (environment-agent-host), and are aimed to understand the phenomenon within a systemic paradigm where the multivaried nature of the phenomenon allows to establish functional relations among drug use, user characteristics and the social and family environment. The hypothetical construction sustained in this paper is: "the magnitude of the risk to fall in a problematical drug use, if someone belongs to the high school population in our country, depends on risk indicators coming from three sources: a facilitating environment, the drug use characteristics (use pattern and drug type) and the student characteristics (demographic, social and psychological)". This article describes the indicators (11 related to the facilitating environment, 8 to the drug use characteristics and 14 to the student), as well as the way to grade them, and the definition of a graphic profile that contemplates four areas. Also, the possible applications in field research and primary care are discussed. We conclude that it is important to have local preventive policies in schools. PMID- 2260001 TI - [Analysis of multiple-cause mortality: a new approach]. AB - Due to changes in mortality patterns, cronic and degenerative diseases have become a major problem in Mexico. Description and explanation of this kind of deaths is difficult by means of a single cause of death. In order to have a better understanding of this fenomenum an analysis of 4021 deaths occurred in Mexico city during april and may in 1985 using multiple cause of death was performed, this analysis take count of all causes reported in death certificates. With the method of multiple cause we found that the number of associated deaths, for example with hypertension and nutritional deficiencies, was considerably greater that when reported as underlying cause. PMID- 2260002 TI - [Chagas disease in Guerrero. Report of 2 cases confirmed with xenodiagnosis]. AB - We report two cases of patients from Costa Chica of Guerrero state, Mexico, with cardiologic problems compatible with Chagas disease. The serologic studies were positive for Indirect Haemagglutination and Immunofluorescence tests. The infection was confirmed with xenodiagnostic using Triatoma mazzotti nymphs. PMID- 2260003 TI - [The use of anthropologic methods for studying the causes of lack of vaccination. The case of Nativitas, Xochimilco]. AB - The relationship between the socio-cultural characteristics of a population and their participation in immunization programs is described in this paper. An anthropological approach was utilized to study the reasons why certain population groups do not participate in the immunization programs or do so inadequately. The study was undertaken in a community south of Mexico City. The paper contains the description of the community's contextual elements, the organization of the medical care services and the participation of the population in the immunization programs. It was found that a wide millieu of socio-cultural factors are related with people's behavior toward vaccination, such as: lack of information about diseases and vaccines, lack of trust on modern health services, and the strong influence of traditional medicine. Clear implications can be derived from the analysis with regards to the need for revision and modification of strategies of the health education programs, in order to promote a wider participation in immunization programs. PMID- 2260004 TI - [Genesis and articulation of public health guidelines in Mexico]. AB - Mexican postrevolutionary health policy has been oriented by changing views on the process of development and of the role that State should play towards the health of specific groups. The article reconstructs how deep-seated health policy values were originated and legitimated. The gestation process is followed through the contest between specific groups and interest in key conjunctures of mexican history. The article proposes that for 1940 three linkage principles between policy makers and beneficiaries had been fully legitimated: the technical, the geopolitical and the corporativist. PMID- 2260005 TI - [Sociodemographic research on family planning: the case of the Health Department]. AB - The Head Office for Family Planning of the Mexican Ministry of Health implemented a program of sociodemographic research for the purpose of studying family planning. On the basis of the sociodemographic profile drawn up in 1983--the year in which said research program was initiated--research needs were gradually identified and then met by means of surveys and monographs for individual states in Mexico. This paper comments on the main features of the research projects that have been carried out. We order to show the data bank which the Head Office for Family Planning has at the present time for studying the phenomenon all of its activities are centered around. PMID- 2260006 TI - [Hygiene practices to be observed by miners working underground. 1896]. PMID- 2260007 TI - [The radiotherapy of epidemic Kaposi's sarcomas in AIDS patients]. AB - From August 1986 to May 1989, 15 patients suffering from Kaposi's sarcoma and serologically proven HIV infections were treated in the Department of Radiotherapy, University of Cologne, Medical Hospital. All patients were male and homosexual. Therapeutic objectives were palliation of pain and functional impairment as well as elimination of the cosmetically disturbing Kaposi's sarcoma. 68 localizations (facial skin, torso, extremities, sole of the foot, penis, oral mucosa and oropharynx) were irradiated. Depending on the individual therapy regimen, photons or high-energy electrons up to a total dose of 26 to 40 Gy, with single doses of 1.8 to 2.5 Gy were applied four to five times a week. In 66% of the cases, complete remission was achieved within the area of irradiation at the dermal or mucosal level, with at most a discrete residual pigmentation of the cluster remaining. Partial remission with at least 50% regression or a distinctive residual pigmentation was achieved in 31%. In 3% of the cases, a less than 50% regression of the Kaposi's lesions were achieved after radiotherapy. There were five local recurrences. Treatment with radiation is an effective local therapy in epidemic Kaposi's sarcoma and yields good functional and cosmetic results and also provides relief from pain. PMID- 2260008 TI - Hypoxyradiotherapy of uterine cervix cancer to decrease of acute side-effects and treatment complications. AB - The authors have reported on preliminary results of hypoxyradiotherapy in the course of external irradiation in patients with uterine cervix cancer from a view point of the occurrence of acute reactions and treatment complications. A mixture of nitrogen and oxygen containing 8.0 to 8.5% of O2 was used to provoke acute hypoxia during irradiation. The applied doses of external irradiation was simultaneously increased by 40%. On the basis of a randomized study with 120 patients, acute hypoxia was found to protect healthy tissues against post radiation damage. When the doses of 96 Gy in the paracervical space and that of 75 Gy in the pelvic wall were applied, acute side-effects decreased significantly if compared with a conventional radiotherapeutic procedure (p less than 0.01). Radiological preconditions for using acute hypoxia in radiotherapy are discussed. PMID- 2260009 TI - [The evaluation of 123I-MIBG scintigraphy in medullary thyroid carcinoma (MTC)]. AB - The diagnostic value of 123-I-MIBG (meta-iodobenzylguanidine) scintigraphy was investigated in six patients with recurrence and/or metastatic spread of a medullary thyroid carcinoma. In no case was there MIBG storage in tumor tissue. Thus, our results show that MIBG scintigraphy is not suitable as a screening method either in the primary diagnostics or the follow-up of medullary thyroid carcinoma. If, however, inoperable metastases have been detected by other diagnostic methods, MIBG scintigraphy is indicated in order to test a potential therapeutic application in these patients. In the imaging diagnostics and follow up of medullary thyroid carcinoma, the examination with 99mTc(V)-DMSA (technetium 99m-dimercaptosuccinate) is markedly superior to MIBG scintigraphy. High resolution cervical sonography is of major importance in the hands of an experienced examiner. PMID- 2260010 TI - [New results with delayed progression in the cell cycle of solid squamous cell carcinomas of the head-neck area after single and fractionated irradiation with cobalt-60 and neutrons]. AB - Cell-kinetic changes of xenograft tumors have been investigated after radiation therapy at different times. The growth-locking lasted clearly longer compared with the one of cell cultures. Against this was there were no cell-kinetic changes between centrum and borders of the xenograft tumors. Adding hypoxic sensitizers a further prolongation of the G2M block could be attained. Fractionated irradiation did not adduce qualitative or quantitative changes of the cell kinetics. There was also no difference between low LET and high LET radiation. PMID- 2260011 TI - Dose-rate distribution under partially shielded beams. AB - We are presenting a method of calculating the dose-rate distributions in partially shielded field. An attenuator was placed in central beam axis and also in an off-axis geometry. The study was made with a Co-60 radiation and with photons generated by 10 and 23 MV Linac at depths, in phantom, from 5 to 30 cm. To obtain the calculated values of dose-rates; the contributions of the three components to the total dose-rate were measured. The calculated dose-rate distributions agree well with the measured data in case of 10 MV and 23 MV radiation. PMID- 2260012 TI - [2 years' experience with a monitoring and recording system for gynecological afterloading irradiation]. AB - A computer program running on a simple desk calculator has been developed for monitoring and recording gynecological high-dose afterloading therapy. For treatment monitoring the multiple-probe AM6-system (PTW-Freiburg) is used which allows for dose measurements in the urinary bladder and the rectum. The probe signals are processed on line in order to indicate the actual dose at the measuring points. After completing the irradiation the treatment is documented. Performing fractionated treatment the measuring data are stored in the computer memory for calculating total accumulated dose. The above-described monitoring and recording [correction of protocolling] system has proven its usefulness during two years of clinical work. PMID- 2260013 TI - Repair of radiation induced damage in two human tumour cell lines grown as spheroids and monolayers. AB - Growth curves of two human tumour cell lines grown as multicellular tumour spheroid (MTS) were used to obtain survival estimates by back-extrapolation after split and single dose irradiation. Neuroblastoma (NB-100) and squamous cell carcinoma (HN-1) single cells from monolayer culture were assessed for repair of sublethal and potentially lethal damage. The extent of repair was calculated on an iso-effect basis. When grown as spheroids squamous cell carcinoma cells showed a higher capacity to repair sublethal damage than neuroblastoma cells. Repair of potentially lethal damage did not contribute to this higher capacity of HN-1 cells, since this cell line was found to be deficient for this type of repair. Using the recovery ratio to estimate the beta-component of the survival curves, it was found that differences in repair capacity were determined by the alpha component of the equation. Our results show the feasibility of back-extrapolating multicellular tumour spheroid growth curves to obtain survival estimates that can be applied to establish sublethal damage repair capacity. PMID- 2260014 TI - Comparison of radiation sensitivity for three cell lines as measured by the cloning assay and the micro-nucleus test. AB - The correlation between cell killing and the induction of micro-nuclei was studied for three cell lines after treatment with gamma radiation to investigate whether the frequency of micro-nucleated cells can be used to determine the radiation sensitivity of a cell type. R1 rat rhabdomyosarcoma cells showed a higher sensitivity for the induction of proliferative death than RUC rat ureter carcinoma cells and V79 Chinese hamster cells which had a similar radiation sensitivity. The frequencies of micro-nucleated cells were measured at 48 hours after the treatment. It was determined by time-lapse cinematography that almost all the cells in the treated cultures had divided at that time. Our results indicate that for these cell lines the correlation between the effectiveness for cell killing and the induction of micro-nuclei was the same, within the experimental errors. PMID- 2260015 TI - Temporary changes of arylsulphatase activity in liver after exposure of AET or MEA pre-treated mice to 60Co gamma-irradiation. AB - The adult male Swiss mice were either whole-body 60Co gamma-irradiated with a single dose of 10 Gy at 1900, or treated intraperitoneally with AET (2 aminoethylisothiouronium bromide hydrobromide) or MEA (cysteamine hydrochloride), in a dose of 400 mg/kg body weight, 15 minutes before irradiation. The measurements of the arylsulphatase (E.C. 3.1.6.1) activity in crude homogenate of liver were done every four hours during 24-hour period, starting at 2000. The enzyme activity towards the artificial substrate p-nitrocatechol sulphate was related to 1 mg of protein, 1 g of fresh tissue and to the whole organ weight. No fluctuations in the activity of arylsulphatase in the control mice were found. There were temporary changes in the enzyme activity expressed in nkat per 1 mg of protein and 1 g of fresh tissue in the irradiated only males, in that related to 1 g of fresh tissue and the whole organ weight in mice injected with AET before irradiation, as well as that calculated in nkat per 1 mg of protein in animals pre-treated with MEA to exposure of gamma rays. Between the particular groups of males, differences in the arylsulphatase activity related to 1 g of fresh tissue and the whole liver weight at 0400 were only observed. 60Co gamma-irradiation influenced the activity of arylsulphatase in liver. AET and MEA modified the effect of exposure of mice to gamma rays on the enzyme activity in a different way. PMID- 2260016 TI - Enlarged tonsils and the effect of tonsillectomy. Characteristics of the dentition and facial skeleton. Posture of the head, hyoid bone and tongue. Mode of breathing. AB - Associations between craniofacial morphology, its development and growth on the one hand and functional factors on the other hand have been eagerly debated in the literature during the last 20 years. The aim of the present thesis, based on five publications, was to evaluate the effect of enlarged tonsils and tonsillectomy on the dento-facial morphology, the posture of the head, the position of the hyoid bone and tongue, and on the mode of breathing. The material comprised 146 Swedish children (66 boys and 80 girls), 5.3-17.3 years old, with a mean age of 10.1 years. Of these children 73 were judged by one otolaryngologist to have enlarged tonsils and were, on this criterion, selected for the investigation. The remaining 73 children comprised the control group and matched the tonsil group for sex and age. The controls were nosebreathers and had no history or symptoms of Ear-Nose-and-Throat-problems. During the investigation 18 of the tonsil children underwent tonsillectomy and 29 remained unoperated. Comparisons between the groups were based on anamnestic and clinical records, measurements on plaster study models and lateral skull radiographs. The results indicate that the children with enlarged tonsils, when compared with the control children, had retroclined lower incisors, protruded upper incisors, shorter lower dental arch, smaller overbite, larger overjet and a greater incidence of lateral crossbites. Furthermore they had retrognathic, posteriorly inclined mandibles, larger anterior lower facial height and skeletal open bite. They also displayed extended headpostures, low posture of the hyoid bone, anterio-inferior posture of the tongue and large oro-pharyngeal depth. 62.5% of the children in the tonsil group were mouthbreathers during the day and 84.7% during the night. The effect of tonsillectomy was mainly associated with a dorsal reposturing of the base of the tongue, change in hyoid bone posture cranially and change to nosebreathing during the night. Furthermore, a decrease in lower inter-molar width and in the tendency to lateral crossbite, as well as a slight increase in the posterior lower facial height had occurred postoperatively. Associations between postural and functional changes mutually, as well as between these changes and morphological changes were found. Enlarged tonsils thus seem to be associated with a characteristic postural and functional pattern, which in its turn seems to have had some influence on the dentition and craniofacial morphology. PMID- 2260017 TI - [Imported diseases in Switzerland: development and perspectives]. AB - During the last years, imported diseases have become more frequent in Switzerland. This is easily explained by the enormous increase of tourism to tropical and subtropical countries. Immigration from these countries has equally seen an important augmentation. The principal imported diseases are still malaria and gastrointestinal infections. Viral infections are rarely diagnosed, with the exception of hepatitis and HIV infection. The prevalence of sexually transmitted diseases is most certainly underestimated. The differential diagnosis of imported skin diseases is still difficult. Rare tropical diseases will probably become more frequent in the coming years as travellers leave more and more the traditional tourist paths. Practitioners have to look out for such problems, and continuous training programmes for them will have to take these new problems into account. Referral centres of infectious diseases should be established in all regions of Switzerland. High priority should be given to the prevention of imported diseases. PMID- 2260018 TI - [Medical advice for travellers]. AB - When counselling travellers to overseas countries, attention should be paid not only to the health and safety conditions within the country of destination, but also to the general health of the traveller and to the personal risk he might take on his journey. Rarely, though, a person has to be discouraged from an overseas trip these days because of a constitutional or medical incapacity, a classification of which is given in the article. It is, however, indispensable to give advice on how to avoid exposure for a number of nuisances and diseases, particularly diarrhea, insect-stings and arthropod borne diseases and STD, as well as accidents. PMID- 2260019 TI - [Vaccinations for travel abroad]. AB - Travel to the developing world by Swiss citizens has been increasing. Vaccine preventable diseases challenges the physician to provide pre-travel advice. Each traveler's itinerary, duration of stay and medical history, including previous immunization, should be reviewed. Vaccinations are required or recommended according to the requirements and the epidemiology of countries being visited. This article summarizes updated recommendations to individual vaccines and immunoglobulins. PMID- 2260020 TI - [Malaria prophylaxis: what is safe?]. AB - Plasmodium falciparum is resistant to proguanil, chloroquine and pyrimethamine/sulfadoxine (Fansidar) in many parts of the world. It can be assumed that in the future resistance to mefloquine and quinine will also increase. This will have important consequences for the recommended schemes for drug prophylaxis. No new drugs suitable for prophylaxis will be on the market in the near future. Neither the combination of mefloquine with pyrimethamine/sulfadoxine (Fansimef) nor the new drug halofantrine will solve the impending problems. It has to be accepted that no absolute protection against malaria infection can be guaranteed by the presently available drugs. In regions with low transmission no permanent prophylaxis but only a standby therapy is recommended. Moreover, personal protection against mosquitoes with pyrethrum impregnated bed-nets and repellents will gain importance. PMID- 2260021 TI - [Diarrhea in returning travellers (etiology, diagnosis and therapy)]. AB - International tourism is constantly expanding and traveller's diarrhea has become a common disease. Although traveller's diarrhea may already have ceased after return, more and more general practitioners are confronted with patients complaining of GUT-symptoms associated with the journey. To manage these patients the precise knowledge of the etiology of traveller's diarrhea and the forms leading to chronic diarrhea is mandatory. This review deals with the etiology of diarrhea after returning home from tropical/subtropical areas and gives special emphasis on adequate diagnosis and treatment. It also points to the importance of parasites as cause of chronic traveller's diarrhea. Parasitic disease needs more often antibiotic treatment than infectious diarrhea due to bacterial agents. We summarize the etiology, the diagnostic and therapeutic approach. PMID- 2260022 TI - [AIDS: risk for tourists and assistants in developing countries?]. AB - In developing countries, AIDS is transmitted in essentially the same way as other sexually transmitted diseases. Therefore the spread of AIDS is also associated with travel. Unfortunately, it is still very difficult to assess the distribution of the infection, especially in developing countries, because in these countries often only 10% of the cases are identified and registered. It can, however, be stated that the highest infection rates are found in Central Africa, in some South American cities, and in the Caribbean. Moderately high rates are found in Western Europe, the USA, Canada and Australia. In the Eastern bloc, in Asiatic countries and in the Pacific area, and in considerable parts of North Africa and South America, the pandemic is only just beginning. Sexual intercourse has been found to be the main means of transmission of HIV infection in developing countries. In addition, further risk factors have been identified; venereal disease, and ulcers on the sexual organs. The risk of parenteral transfer is also considerable, because of inadequate testing of blood for transfusion, and the lack of satisfactory facilities for sterilisation. For tourists and development workers, the risk of infection depends very much on their own behaviour when they are overseas. Though the risk of infection is somewhat higher in developing countries, it can clearly be greatly reduced if travellers are adequately informed and are thus equipped to take the necessary precautions. PMID- 2260023 TI - [Current trends in parasitological diagnosis]. AB - During the past few years a number of modern techniques has found its way into the discipline of diagnostic parasitology. The scale of these new tool ranges from highly sensitive and low toxic fixatives for intestinal protozoa, to rapid detection methods for malarial parasites and to the techniques of modern biology, like hybridoma and DNA technology. PMID- 2260024 TI - [Fundamentals of immunodiagnosis exemplified by parasitic infections]. AB - The rapid development in the fields of immunology, biochemistry and biotechnology had a strong impact for immunodiagnosis. The use of monoclonal antibodies, recombinant antigens and synthetic peptides has considerably improved many diagnostic techniques. However, considerations on the meaning of a test result (on the basis of the concept of predictive values) are of prime importance: false use and inappropriate knowledge of the limitations of a technique can lead to diagnostic errors. PMID- 2260025 TI - [Imported diseases: information, communication and continuing education]. AB - With the increase of international travel and immigration, imported diseases have become more important in recent years in Switzerland. Diagnosis and therapy of imported diseases were simplified over the last years, whereby prophylaxis is still a complex problem, i.e. difficult to standardize. The article analyses information problems and presents what is done in Switzerland in this regard for each concerned group (travellers, practitioners and chemists, vaccination centers). Written information and courses for continuing education are generally available and adequate, but their impact is insufficient, perhaps because of the time constraints they impose. Electronic communication systems are not yet efficient due to their low access quota (spreading and standardization of the equipment), but the situation in regard to information as well as to continuing education will be better, as soon as these systems are accessible to the large public and well adapted, easy to use programmes will have been developed. PMID- 2260026 TI - [Medical examination of asylum seekers at entry]. AB - It was the purpose of this analysis to summarize the salient findings made with the initial medical examination of asylum seekers in Switzerland. The evaluation covered the period from 1984 to 1987. The epidemiologic impact of diseases discovered by this screening and the logistic problems encountered with the decentralization of the program have required a modification and a reassessment of the necessary measures. As a consequence, indiscriminate stool examinations for bacteria and parasites have been abandoned. These examinations had required a considerable investment which is not considered to be justified by the limited epidemiologic significance of these intestinal pathogens. More emphasis is being placed on improved tuberculosis control measures, by providing concise guidelines for screening, prevention, and treatment. A simplified procedure for hepatitis B screening is to be maintained for the time being, conditional upon special emphasis on children, adolescents and adults of reproductive age groups. Hepatitis B vaccination of seronegative persons is a part of the standard basic immunization program. The core of the screening program and the delivery of initial preventive measures is to be carried out in the federal registration and transit centers for asylum seekers. PMID- 2260027 TI - [From tropical medicine to medicine in the tropics--priorities in the control of transmissible diseases]. AB - The major health problems of developing countries are still caused by communicable diseases. Along with the raise of the living standards and substantial urbanization processes in many parts of the third world, a shift towards chronic noncommunicable diseases of adults, which are costly to control, can be expected. Health priorities are not only determined by the biomedical view assessing morbidity and mortality patterns, but also by the ranking of perceived health problems, symptoms and signs by the population concerned. Incorporating these aspects greatly increases the acceptance of health interventions and can stimulate community involvement. The recent advances in the field of diagnosis, therapy, prophylaxis as well as in the implementation of primary health care imply the need to emphasize the operational aspects of intervention programmes such as diagnostic accuracy, compliance of providers and users and coverage. These elements are the crucial determinants of the community effectiveness of any technology and will provide the cornerstones for sustainability besides careful evaluation and monitoring of a health intervention. PMID- 2260028 TI - [Follow-up of elderly patients after emergency hospitalization for severe drug reactions]. AB - Forty-one observations concerning persons aged over sixty-five hospitalized for adverse drug reactions in the Emergency Service of Clermont-Ferrand University Hospital were collected and analysed by the Adverse Drug Reaction Monitoring Centre. The symptoms were predominantly haemorrhage, particularly digestive, connected with the use of oral anticoagulants, salicylates and anti inflammatories. The follow-up of the thirty-one most severe cases (hospitalization over 48 h and/or initial resuscitation) was undertaken in hospital and other care centres. In seventeen cases, complications occurred linked to the hospitalization (especially infections and neuropsychic complications) or to the adverse reaction itself through the measures taken to correct it (particularly cardiovascular complications). The hospitalization revealed hitherto undetected conditions in twelve patients, thereby allowing the prognosis to be improved. This positive side hardly outweighs the detrimental effects of adverse drug reactions in elderly subjects (six deaths and four irreversible incapacitations). Thus vital and social prognosis of elderly appears greatly damaged by adverse drug reactions. PMID- 2260029 TI - [Inventory of questions posed at a Regional Pharmacovigilance Center. Discussion about a possible coordination of informatics]. AB - All the requests (162) from the 1st to the 31th of december 1988 (a period of one month) are analysed by the Paris Fernand-Widal ADR Monitoring Centre. The requests are classified as following: 74 pharmacological consults (39 about pregnancy, 9 for breast-feeding, 3 neonates or children, 2 about G6PD deficiency, 3 guide-lines after a therapeutic error, 3 requests for treatment of ADR, and 15 miscellaneous). 5 ADRs notified and reported to an other nearest Centre to the caller and 3 diagnosed latter as an ADR 49 ADRs registered turn to a request because of lack of information (age: 15; sex: 18; name: 1; address: 31,) or faithfullness (4) or several reasons (18). 31 general information about drugs. Usually, physicians request the Monitoring Centre but recently patients request directly the Centre; specially during pregnancy. The progressive number of the questions makes computerization necessary. A single system appears to be essential for all the Regional Centres to improve the quality of the answer and for the new ADR's alert. PMID- 2260030 TI - [Financial analysis of hospitalizations for adverse effects of drugs. The economic role of the Regional Pharmacovigilance Center]. AB - Authors look at different methodological estimations of costs induced by hospitalizations for side effects of drugs: individual, global and budgetary estimations. Only the two last ones are possible today. Results are sufficient to demonstrate the economic importance of a Pharmacovigilance Centre for the Hospitals that have got such a structure. PMID- 2260031 TI - [Computerized data processing in the Pharmacovigilance Center of Bordeaux Aquitaine. Analysis of clientele of the Center]. AB - Practitioners inquiries addressed to our Drug Information Centre are computerized since 1986. Their analysis allows to pinpoint special problems and needs for practitioners information, and to detect new adverse drug reactions. Time series analysis of calls (according to the practitioners specialities or geographic stay) allows to evaluate the effectiveness of the services provided by the Bordeaux Drug Information Centre. PMID- 2260032 TI - [Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance]. AB - One hundred and eighty six cases of amineptine abuse were reported to the Regional Centres of Pharmacovigilance or to the Laboratory Eutherapie during a ten year period, between 1978 and february 1988. The analysis was carried out on 155 cases. The principal characteristics of overconsumption are: a predominance of females; the existence of risk factors in 2 out of 3 cases; the absence of correlations between the prescribed dosage, the duration and the importance of abuse; the constant search of a psychostimulant effect; a good clinical acceptability in most cases, but the risk of acne and psychic disturbances must be emphasized; withdrawal difficulties, obtained in only 48 patients (for at least one month). Psychic symptoms on withdrawal were variable and it was not possible to identify a syndrome. The risk of abuse seems to be rare, nevertheless, one must know this occurrence and respect the recommanded dosage. In patients with certain psychiatric illnesses, and especially in patients with risks factors, drugs with stimulant properties should be prescribed with caution. PMID- 2260033 TI - [Evaluation of the pharmacovigilance follow-up of zidovudine]. AB - A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease. PMID- 2260034 TI - [Therapeutic high-doses of digoxin with blood level determinations in 31 out of 150 elderly hospitalized patients treated over a year]. AB - The assay by immunoenzymatic method of the blood level of digoxine in 150 old people, (m = 79 years), hospitalized during one year shows a level of more than 2 ng/ml in 31 of them, (m = 2.91 ng/ml). However, the dosage is normal or low, m = 0.206 mg/j. A renal impairment often discussed is not the mechanism: 17 patients with a blood creatinine over 135 mumol/l have a mean blood level of digoxine of 2.98 ng/ml for 2.91 in the 14 another ones without renal impairment. Physicians should be still more cautious when prescribing digoxin. PMID- 2260035 TI - [Iatrogenic fluorosis. 2 cases]. AB - Two new cases of osteofluorosis are presented. They are attested by the existence of a bone X-ray densification, by histological lesions of hyperosteoidosis and a large increase in the fluorine content. One is a 61 year-old man who consumed 2.5 l a day of Vichy St-Yorre (a mineral water containing 8 mg of fluorine ions per litre) during 11 years; the other, an 86 year-old man who during 20 years took 500 mg of niflumic acid a day, a non-steroidal anti-inflammatory drug containing 3 fluorine atoms per molecule (i.e., 50 mg fluorine per 250 mg gellule). Both these hypertensive patients had severe renal insufficiency. These two observations serve as a reminder of the indispensable precautions to be observed when prescribing fluorine salts in the treatment of post-menopausal osteoporosis: at least the plasma creatinine level should be available in order to calculate the endogenous creatinine clearance and any possible supplementary intake of fluorine salts should be checked. PMID- 2260036 TI - [Course of blood creatinine during repeated injections of cisplatin. Influence of drug combinations]. AB - Cisplatin (CDDP) is known to induce nephrotoxicity. In this retrospective study, we have investigated the evolution of plasma creatinine in long term therapy with CDDP. We have studied case history, mode of administration of CDDP and associations with other chemotherapeutic agents or drugs which could potientiate CDDP renal damage (non steroidal anti-inflammatory agents, analgesics, antibiotics, antihypertensive agents, diuretics and contrast media). Mean creatinine concentration versus time rises significantly. This elevation is significantly higher in patients with hypertension, diabete, one functional kidney, or abdominoperineal irradiation. The association with other drugs has not proved a real influence on creatinine evolution. PMID- 2260037 TI - [Fever caused by fipexide. Evaluation of the national pharmacovigilance survey]. AB - Fourteen cases of drug fever due to fipexide were reported by a retrospective survey of a National Network of French Pharmacovigilance. 8 women, 6 men (mean age, 52 years), presented a sudden fever with a mean onset delay of 7 days after the first cure (range 2-12 days). In five cases, drug fever was the only manifestation; in other cases, it was associated with systemic or cutaneous signs. Eosinophilia was frequent (8 cases) and once, a chest picture showed an interstitial pneumonitis. Fever disappeared promptly after discontinuation of the drug and for ten patients, the rechallenge was positive within a short time. The clinical picture and laboratory tests are discussed and suggest an hypersensitivity reaction. PMID- 2260038 TI - [Recurrent psychiatric manifestations during malaria prevention with mefloquine. A case report]. AB - The authors report the case of a 22 years old woman without psychiatric antecedent who started a prophylaxis with mefloquine for a journey in a chloroquino resistant area. The first tablet induced an acute psychiatric syndrome which lasted five days; the second tablet induced the recidive of the psychiatric data and a suicide attempt by drowning. PMID- 2260039 TI - [A one-year evaluation of collaboration between an hospital allergy unit and a regional center of pharmacovigilance]. PMID- 2260040 TI - [When can the cases of toxic or adverse effects of drugs be rejected? 80 cases]. PMID- 2260041 TI - [Fixed pigmented erythema. Value of cutaneous patch-tests of drugs. A case report]. PMID- 2260042 TI - [Severe acute hepatic involvements caused by exifone]. PMID- 2260043 TI - [Acute drug hepatitis. A practitioner's diagnosis]. PMID- 2260044 TI - [Agranulocytosis caused by paracetamol. A case report]. PMID- 2260045 TI - [Zolpidem and hypnotic hallucinations]. PMID- 2260046 TI - [Beta-blockers and migraine. Efficacy of time-release propranolol versus placebo]. AB - The efficacy and safety of long-acting propranolol (LA.P) 160 mg once-daily in the prophylactic treatment of migraine were tested against placebo in a multicentric, double-blind, randomized study comparing the two groups in a parallel manner over a treatment period of 12 weeks, and following a 4 week placebo run-in period. Fifty-five out of the 74 patients who entered the trial included at the end of the run-in period. Forty-one patients completed the study. Out of the 14 patients who withdrew from the study, none discontinued because of side-effects. The statistical analysis was done according to the "intention to treat" principle. LA.P was significantly more efficient than placebo in reducing the frequency of migraine attacks (p = 0.01 by variance analysis). LA.P reduced the average number of monthly crises by 48% on day 84. There was a slight but significant reduction of the systolic blood pressure and heart rate in the erect position. There was no significant difference between LA.P and placebo regarding either the number of complaints or the number of side-effects elicited out of an 17 item questionnaire. None of the observed side effects led to a withdrawal of treatment. PMID- 2260047 TI - [Delayed acute pancreatitis after treatment with L-asparaginase. A case report]. PMID- 2260048 TI - [Cardiogenic shock resistant to sodium lactate with high-dose of cibenzoline]. PMID- 2260049 TI - [Dose response to 3 dosages of Langoran 40 mg, 80 mg and 120 mg]. PMID- 2260050 TI - [Tidsskrift for den Norske Laegeforening. Register index. 1990]. PMID- 2260051 TI - [Pain schools and pain clinics]. PMID- 2260052 TI - [Tuberculosis today and in the future]. PMID- 2260053 TI - [Symptomatic hyponatremia]. PMID- 2260054 TI - [Pain school. Ambulatory treatment of patients on long-term sick leave due to muscular pain. A 1-year follow-up study]. AB - 55 patients with chronic musculoskeletal pain who had been on sick leave for at least six months took part in a four week outpatient treatment programme. The programme was multidisciplinary and consisted of a combination of physical activity, formal lectures about health matters and individual consultations with doctor, psychologist, social worker, nurse and sports instructor. Pretreatment Minnesota Multiphasic Personality Inventory and Health Locus of Control showed the patients to have a typical chronic pain profile. The tests did not discriminate between those who had a favourable outcome and those who did not. At one year follow-up, 21 of the 55 patients had returned to work despite unchanged subjective intensity of pain. PMID- 2260055 TI - [Group therapy of patients with chronic pain]. AB - 51 patients suffering chronic pain, with different diagnoses, were treated in groups as outpatients using a cognitive behavioural approach. Groups of 7-8 patients met for two hours a week for six weeks. The groups were led by a team consisting of a clinical psychologist, a physiotherapist and a doctor. The patients learned about different aspects of pain, self-exercise and relaxation by selfhypnosis. Group dynamics was used to strengthen self-esteem, facilitate learning and encourage a change of attitude towards pain. Each patient answered a questionnaire about activities, level of pain, drugs and psychological symptoms before and immediately after treatment, and at follow-up one year later. At follow-up, 43% were less depressed, 70% felt less pain and 50% were more active and used less drugs. PMID- 2260056 TI - [A 10-year tuberculosis case load. Symptoms, clinical findings and laboratory data of patients in Glittre Sanatorium]. AB - This article presents retrospective data from a ten-year material consisting of 426 patients with tuberculosis. There was a large difference in age between Norwegian and foreign patients. Median duration of symptoms before treatment was 15 weeks. The most common extrapulmonary form was lymph node tuberculosis, with a striking overpercentage of females. General symptoms were more common among patients with pulmonary tuberculosis than among patients with extrapulmonary forms. In 43% of the patients with pulmonary tuberculosis no abnormal signs were registered by auscultation. Febrile patients became quickly afebrile after start of treatment. 83% of the patients were tb culture-positive. 9.5% of the isolates tested for resistance showed reduced sensitivity to one or more antituberculous drugs. Chest x-ray manifestations were more common in the right than in the left lung. Older people are the main source of tuberculosis in Norway. One should be particularly aware of this diagnosis in immigrants from the Third World. PMID- 2260057 TI - [Treatment of tuberculosis. Drug combinations, therapeutic problems and results in a 10-year case load]. AB - The article describes the treatment of tuberculosis in 426 patients over a period of ten years. The length of treatment decreased during the period. The standard treatment was isoniazide and rifampicin, usually with initial administration of pyrazinamide. In pulmonary tuberculosis (n = 334) the median bacteriologic conversion time was five weeks. In 69 patients the medical regimen had to be changed because of side effects. Of the primary antituberculous drugs, isoniazide was the one producing the highest frequency of side effects. 31 patients showed lowered sensitivity to the usual antituberculous drugs and were treated with varying combinations of second line drugs. In two cases surgery was necessary in order to achieve bacteriologic conversion. Ten patients died of tuberculosis in spite of treatment. Five patients with pulmonary tuberculosis suffered a relapse after treatment. No relapse was noted among patients with extrapulmonary tuberculosis. There were large differences between the different pulmonary treatment centres in Eastern Norway as regards how they practised the Norwegian control routines. PMID- 2260058 TI - [Methotrexate induced pulmonary disease]. AB - Methotrexate may cause pulmonary side effects. Two cases of methotrexate-induced fibrosing alveolitis are reported. One of the patients died from perforated gastric ulcer, the other was successfully treated with systemic steroids. The pulmonary side effects of methotrexate are reviewed. The most common clinical manifestation is fibrosing alveolitis. Pulmonary fibrosis and acute, non cardiogenic pulmonary oedema are rare. PMID- 2260059 TI - [Pulmonary damage caused by ski waxing]. AB - It is well known that inhalation of pyrolysis products of perfluorinated hydrocarbons (e.g. Teflon) may result in polymer-fume fever and even pulmonary oedema. A new type of ski wax has recently been introduced, a powder consisting of low-molecular perfluorinated hydrocarbons. We report a case history of a man who developed an attack of polymer-fume fever and pulmonary oedema after smoking cigarettes contaminated with this ski wax. Inhalation of vapour from ski waxes melted at low temperatures may also be harmful to the lungs. PMID- 2260060 TI - [Severe, symptomatic hyponatremia]. AB - Severe hyponatremia (serum sodium levels less than 120 mmol/l) is associated with increased morbidity and mortality. We report three cases where patients developed hyponatremia and severe neurological manifestations after medical treatment. The first two patients experienced episodes of general seizures and coma, but recovered in 24 hours without neurologic sequelae after correction of the electrolyte disturbance. The third patient developed the syndrome central pontine myelinolysis with pseudobulbar palsy and quadriparesis. Marked improvement occurred, however, and in three months the patient was almost completely recovered. The development of hyponatremia deserves special attention in connection with the use of diuretics, infusion of sodium-free carbohydrates and immediately after operation. PMID- 2260061 TI - [Therapeutic methods used in psychiatric departments and homes for children and adolescents in Norway]. AB - In November 1988 a point prevalence questionnaire study was carried out to evaluate which methods of treatment were given to child and adolescent psychiatric inpatients in Norway. Special emphasis was laid on to what extent psychotropic drugs are prescribed. All child and adolescent psychiatric institutions participated in the study and completed questionnaires on every inpatient on one particular day, 295 patients in all. The study confirms the family-oriented approach within child psychiatry and discredits the notion that children are drugged by psychiatrists. The study raises the question of how the chain of treatment should be organized to optimalize the available resources, and how methods should be differentiated in regard to the different diagnostic groups. It also emphasizes the need for continuous evaluation of the therapeutic activity. PMID- 2260062 TI - [Solvent-induced lesions in Trondelag. How were they treated?]. AB - The article presents the most important results of a follow-up study of 60 patients with solvent induced encephalopathy, carried out 3-5 years after diagnosis. Factors concerning health, work and social life were registered. These encephalopathies seem to remain stable after cessation of exposure to solvents. The majority of the patients did not fully understand the diagnosis. Only a minority of the patients followed recommendations concerning further work and exposure to solvents. The disease has major consequences for the social well being of the patients, and they do not seem to receive adequate support from the social welfare authorities. PMID- 2260063 TI - [Liposuction. A new and valuable tool in the armamentarium of the surgeons]. AB - Since its introduction in 1975 liposuction has become an increasingly popular technique and, in the United States today, is the most commonly performed procedure in cosmetic surgery. However, this technique is also useful in the treatment of a number of other conditions such as gynecomastia and lipomas/lipomatosis, and as an adjuvant procedure to surgical procedures such as reduction mammoplasty, abdominoplasty, and defattening of flaps. The article describes the technique and its indications and possible complications. PMID- 2260064 TI - [The molecular function of oncogenes]. AB - Cancer represents a disruption of the processes in normal cells. To understand cancer, and thereby develop effective treatment, it is necessary to learn about normal reactions in the cells, and their connections. Thus cancer research has been an important source of knowledge about normal cells. Oncogenes are genes that transform normal cells into cancer cells. More than 60 oncogenes have been discovered, and many malignant diseases have been linked to these genes. Human cells contain a normal version of oncogenes, known as protooncogenes, which participate in the normal, cellular processes. This discovery has been of major importance for our understanding of cancer and molecular genetics. PMID- 2260065 TI - [Correction of severe hyponatremia]. AB - Profound hyponatremia is a life-threatening emergency which can result in permanent neurological damage. The rate at which severe hyponatremia should be corrected is the focus of clinical debate. It is important, however, to differentiate chronic from acute hyponatremia and to develop a plan for correcting hyponatremia. A treatment regime is suggested. PMID- 2260066 TI - [Transtracheal aspiration]. PMID- 2260067 TI - [News on treatment of osteoporosis with fluoride]. PMID- 2260068 TI - [Drug therapy in arthrosis]. PMID- 2260069 TI - [Suicide investigation--a psychological autopsy]. AB - The most disastrous complication for a psychiatric team occurs when the patient commits suicide. The reactions of the personnel involved with the patient are similar to the reactions of the bereaved: denial, guilt and shame, aggression and accusation, relief. By psychological autopsy we mean a structured group meeting where all the factors leading up to the suicide are discussed and the reactions of the personnel ventilated. This is different from psychological debriefing, where the primary aim is to ventilate the reactions of the involved personnel without analyzing what went wrong. The article describes how psychological autopsy has been conducted for more than 15 years at the psychiatric ward in the Central Hospital in Stavanger, Norway. PMID- 2260070 TI - [Peroperative ultrasonography in surgery of liver metastases in colorectal cancer. A obligatory examination]. AB - It is not easy to evaluate the real actual benefit of resection of liver metastases from colo/rectal carcinoma. This is partly due to inaccurate preoperative imaging of the metastases. The given sensitivity of the various imaging techniques varies widely. Peroperative ultrasonography is more sensitive than the other techniques. It will influence the operation for metastases in 15 40% of the cases. This technique should therefore be compulsory in connection with surgery for liver metastases. PMID- 2260071 TI - [Indoor climate and occupational health--experiences from Hedmark and Oppland]. AB - We discuss investigations of 22 buildings where users had complained about indoor air and climate. Complaints about "dry air" were the most frequent. Insufficient care and cleaning of the furnishings and technical installations were demonstrated in 17 buildings. Proper documentation and instruction manuals for the maintenance of the installations were not found in any of the buildings. The personnel responsible for the installations had not received adequate instructions. Free man - made mineral fibres (MMMF) were found in the indoor environments in 12-15 of the buildings, originating from the furnishings or the technical climate-installations. Ten of the premises had filted carpets. In at least 13 of the buildings the indoor air temperature was too high, which exacerbated the problems. Better information and a higher level of understanding of problems relating to the indoor climate seems to be needed for all persons involved with these problems. PMID- 2260072 TI - [Local procoagulant activity--an important pathogenic mechanism in Crohn disease?]. AB - The etiology of Crohn's disease is unknown. Observations suggest that some sort of luminal agent enters the intestinal mucosa and elicits the special inflammatory reaction. Immunological mechanisms seem to be important. A related but so far largely unrecognised reaction is local activation of the external coagulation system by induction of thromboplastin (tissue factor) activity on the surface of endothelial cells and macrophages. This local procoagulant activity might initiate the formation of thromboses in small arteries in the intestinal wall. Recent studies indicate that microinfarcts due to arterial thromboses at the level of the muscularis propria may be an important pathogenetic mechanism in Crohn's disease. PMID- 2260074 TI - [End of the drug monopoly in Norway?]. PMID- 2260073 TI - [Chronic pain--a chronic headache for health services?]. AB - Chronic, non-malignant pain is becoming a problem of increasing dimension in our national health system. Chronic pain is essentially different from acute pain. Therefore, it must also be treated by different means and from a different therapeutical angle. Doctors and other therapists often meet the patient with chronic pain with mild rejection and other defensive reactions. This is not only unprofessional but also unjust towards the patient. Further more it helps to turn these patients into excessive consumers of health services. This article proposes two distinct measures that can both humanize the treatment of chronic pain, and make it more economic: Training/re-education of doctors and therapists in the treatment of chronic pain. Ambulatory group treatment for patients with a cognitive/behavioural profile. PMID- 2260075 TI - [Production of ocular prostheses in Norway]. PMID- 2260076 TI - [A national database for information on disease prevention and health promotion in the USA]. PMID- 2260077 TI - [Trichotillomania]. PMID- 2260078 TI - [The nematode Haemonchus contortus: antigenic characterization and immune response in rabbits and sheep]. AB - In the first part of the study, various tissues of L3 larvae and adult Haemonchus contortus were examined by indirect fluorescence to investigate their antigenicity. L3 larvae were studied in immunoblots as well. The following tissues contained antigens: the sheath and cuticle of L3 larvae; and the cuticle, muscles, epithelium and glandular tissue of the oesophagus and sheath of the spicules of adult nematodes. On the cuticle of exsheathed L3 larvae, we detected by light-microscope slightly raised patches: places where the cuticle differs from the surrounding cuticular morphology. We suggest that the patches are comparable to those found on exsheathed L3 larvae of the horse. Whether the patches produce excretory or secretory antigens or both is unknown, however. Somatic soluble extracts of L3 and adult worms were found to be complex mixtures of proteins by polyacrylamide gel electrophoresis. Results in immunoblots of L3 larvae suggested that the region between the 42 kDa protein and the 18 kDa protein may contain antigens specific for H. contortus. We injected rabbits with the 42-25 kDa fraction of the L3 larvae. The rabbit sera were probed in immunoblots with the total somatic soluble L3 extract for the presence of antibodies. Antibodies reacted with antigens in the 42-25 kDa fraction, however, cross-reactions occurred with antigens in the L3 fractions that were not injected into the rabbits. We found that antibodies against phosphorylcholine were induced and suggest that these cause some of the cross-reactions. In the second part of the study sheep were infected orally with H. contortus and their lymphocyte responses towards L3 antigen and mitogen were measured in a lymphocyte stimulation test. Lymphocyte responses to L3 antigen are expressed in a stimulation index. Two groups of worm-free raised sheep were inoculated (sheep older than 1 year and lambs that were 4 to 6 months old) as well as a group of hyperimmunized sheep. Some sheep were inoculated only once; others were inoculated and then challenged. Lymphocytes of sheep that were hyperimmunized replicated rapidly in the test resulting in significantly higher stimulation indices than those recorded for the lymphocytes of all other sheep. After inoculation the enhanced response further increased. We explain these lymphocyte responses as a result from the immunological memory induced during the hyperimmunization. Lymphocytes of sheep over 1 year old only respond in the test when sheep are infected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2260079 TI - [The polymerase chain reaction]. AB - The polymerase chain reaction (PCR) is a technique that enables us to prepare in a test tube billions of copies of a specific piece of DNA. The principles and practical aspects of the PCR are exposed. Within veterinary medicine the most important applications are expected to be i) the diagnostics of infectious diseases and ii) the detection of genetic disorders or desired genetic traits. The PCR can be carried out on a multitude of samples ranging from mummies to paraffin-embedded tissue specimens. However, inhibitors present in e.g. serum, urine and faeces have to be removed. PMID- 2260080 TI - [A case of heat shock]. PMID- 2260081 TI - [Exocrine pancreatic insufficiency in the dog]. PMID- 2260082 TI - Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. AB - Cultured human dermal fibroblasts suspended in a rapidly polymerizing collagen matrix produce a fibroblast-populated collagen lattice. With time, this lattice will undergo a reduction in size referred to as lattice contraction. During this process, two distinct cell populations develop. At the periphery of the lattice, highly oriented sheets of cells, morphologically identifiable as myofibroblasts, show cell-to-cell contacts and thick, actin-rich staining cytoplasmic stress fibers. It is proposed that these cells undergoing cell contraction produce a multicellular contractile unit which reorients the collagen fibrils associated with them. The cells in the central region, referred to as fibroblasts, are randomly oriented, with few cell-to-cell contacts and faintly staining actin cytoplasmic filaments. In contrast it is proposed that cells working as single units use cell locomotion forces to reorient the collagen fibrils associated with them. Using this model, we sought to determine which of these two mechanisms, cell contraction or cell locomotion, is responsible for the force that contracts collagen lattices. Our experiments showed that fibroblasts produce this contractile force, and that the mechanism for lattice contraction appears to be related to cell locomotion. This is in contrast to a myofibroblast; where the mechanism for contraction is based upon cell contractions. Fibroblasts attempting to move within the collagen matrix reorganize the surrounding collagen fibrils; when these collagen fibrils can be organized no further and cell-to-cell contacts develop, which occurs at the periphery of the lattice first, these cells can no longer participate in the dynamic aspects of lattice contraction. PMID- 2260083 TI - Interstitial macrophage subpopulations: responsiveness to chemotactic stimuli. AB - Recent data suggest that interstitial macrophages are a heterogeneous group of cells with several subpopulations. This study was undertaken to determine if there is heterogeneity among rat interstitial macrophage subpopulations ability to respond to chemotactic stimuli. Alveolar macrophages were harvested and separated into density-defined fractions by centrifugation through a continuous iso-osmotic gradient of colloidal silica. Unfractionated and density-defined interstitial macrophages were then characterized as to their ability to migrate towards F-Met-Leu Phen and zymosan activated serum. Interstitial macrophages of density 1.053 and 1.083-1.097 gm/ml were found to have the greatest migrational movement towards F-Met-Leu-Phen which was lower than the unfractionated population. Interstitial macrophage subpopulations migrational movement towards zymosan activated serum exhibited a major peak by macrophages of density 1.053 gm/ml and a minor peak by macrophages of density 1.083-1.097 gm/ml which was lower than the unfractionated population. These results demonstrated that interstitial macrophages are heterogeneous in their migrational ability towards the chemotactic stimuli F-Met-Leu-Phen and zymosan activated serum and that there may be a cooperative interaction between the subpopulations which affects macrophages migrational ability. PMID- 2260084 TI - Difference in enzymatic sulfation of bile acids between the mouse and rat. AB - Species difference in bile acid-sulfotransferase (BAST) activity was studied between the mouse and rat. Cytosol fractions of the liver, kidney, small intestine and large intestine were incubated with bile acids and 3' phosphoadenosine-5'-phosphosulfate. The mouse liver showed BAST activity for lithocholic acid, taurolithocholic acid and taurochenodeoxycholic acid, whereas the rat liver and kidney had the activity for taurodeoxycholic acid in addition to these compounds. The highest activities were found in the mouse liver and rat kidney. The mouse small intestine showed weak activity only for lithocholic acid. No activity was found in other organs. BAST was inactive towards taurocholic acid, 7 alpha- or 12-monohydroxy-5 beta-cholanoic acid. Optimal pH of liver BAST in the two species was different from that of the rat kidney. BAST of the mouse liver showed the highest activity without addition of Mg2+, whereas that of the rat liver and kidney showed enhancement by exogenous Mg2+. These results indicated that the distribution and characteristics of mouse BAST was different from rat BAST. Such difference should be reminded in any animal study involving the two species. PMID- 2260085 TI - Mutagenicity of nitrite-treated soy sauce in Chinese hamster V79 cells. AB - Mutagenicity of 4 kinds of Japanese soy sauce and tyramine, which is a precursor of a mutagen (3-diazotyramine) and present in soy sauce, after nitrite treatment under a yellow lamp was studied in Chinese hamster V79 cells with 6-thioguanine (TG) as a selective marker. The frequencies of mutation caused by nitrite-treated samples of soy sauce increased in the V79 cells in a dose-dependent manner. Four kinds of nitrite-treated soy sauce induced 139 to 473 TG-resistant mutants per 10(5) clonable cells per milliliter of soy sauce equivalent in the cells. Nitrite treated tyramine was also mutagenic for the cells; it induced 8.6, 13.3, and 18.3 TG-resistant mutants per 10(5) clonable cells at concentrations of 20 micrograms, 56 micrograms, and 112 micrograms, respectively. PMID- 2260086 TI - A semiquantitative filter paper method for screening for lactic acidemia. AB - A specific semiquantitative measurement of lactate suitable for use in screening is described. In this method lactate in dried blood on filter paper is stained with an indicator dye. PMID- 2260087 TI - The magnetocardiographic diagnosis of right ventricular diastolic overload. AB - The diagnosis of right ventricular overload is often difficult by the electrocardiogram (ECG) when it is associated with right bundle branch block (RBBB). In this study, we examined the usefulness of the MCG in diagnosis of right ventricular diastolic overload and clarified the features of the magnetocardiogram (MCG) of patients with right ventricular overload with RBBB. In our previous studies, we found that MCG criteria shows higher sensitivity in diagnosis of right ventricular hypertrophy, but the criteria showed higher false positivity in patients with RBBB without any underlying disease (RBBB group). Therefore, we set different MCG criteria for right ventricular diastolic overload (RVO-d) as follows based on the mean +/- 2SD of the RBBB group: 1) R wave at C-3 (Rc-3)greater than or equal to 25 x 10(-12)tesla, 2) S wave at F-4 (SF-4)greater than or equal to 11 x 10(-12)tesla. In patients with a right ventricular pressure of more than 50 mmHg, the MCG criteria showed higher sensitivity and specificity than the ECG criteria. These results suggest that the MCG is useful for diagnosis of right ventricular diastolic overload with RBBB. PMID- 2260088 TI - A comparison of terminal airway remodeling in chronic daily versus episodic ozone exposure. AB - This study compares centriacinar changes by ultrastructural morphology and morphometry following daily versus episodic ozone exposure in rats. Three groups of rats were exposed to air, 0.95 ppm ozone 8 hr daily for 90 days, and 0.95 ppm ozone 8 hr daily in seven successive 5-day episodes separated by 9-day recovery periods for a total of 89 days. Sections from the left lung and dissected acini from the right middle lobe were studied by light and electron microscopy. The centriacinar lesion following episodic exposure was similar but diminished in severity compared to that of rats exposed daily. Damage following episodic exposure appeared to be more than predicted by an exposure regimen which delivered 35% of the total ozone dose during daily exposure. The total volume of affected parenchyma was similar following both exposures. Respiratory bronchiole formation increased following both exposures but this was only statistically significant following daily exposure. The most severe epithelial damage was at the tips of alveolar septa in alveolar ducts distal to the respiratory bronchiole. Interstitial thickness in the injured respiratory bronchiole and proximal alveolar duct increased significantly and similarly following both exposures. Epithelium along the respiratory bronchiole of daily exposed rats was more differentiated. In the episodic group, respiratory bronchiole and alveolar duct epithelium consisted of a range of intermediate, less differentiated bronchiolar or alveolar epithelial cells. The episodic exposure resulted in a diminished lesion, but there appears to be some cumulative effect of repeated exposures with respiratory bronchiolar and alveolar duct epithelium in a more dynamic state of injury and repair. PMID- 2260089 TI - Immunosuppression by aldicarb of T cell responses to antigen-specific and polyclonal stimuli results from defective IL-1 production by the macrophages. AB - In the present study we investigated the immunomodulatory effects of aldicarb, a carbamate pesticide, on T cells activated by a number of different ways. When C3H mice were injected intraperitoneally with a single dose of Aldicarb, 0.005-50 micrograms/kg body wt, and their spleen cells were stimulated with T cell mitogens such as concanavalin A (ConA)3 or anti-CD3 monoclonal antibodies (mAb), a decreased responsiveness was detected when compared to the control mice. Aldicarb administered at concentrations less than 0.005 microgram/kg body wt failed to cause significant immunosuppression. Interestingly, when purified T cells from immunosuppressive doses of aldicarb-treated mice were stimulated with ConA in the presence of irradiated control macrophages, the defective T cell response was no longer demonstrable. Also, purified control T cells stimulated with ConA in the presence of irradiated macrophages from aldicarb-treated mice showed decreased responsiveness. Similar observations were made using anti-CD3 mAb to activate the T cells, inasmuch as whole spleen cells from aldicarb-treated mice showed decreased responsiveness to anti-CD3 stimulation, whereas purified T cells in the presence of irradiated control macrophages showed normal reactivity. The fact that aldicarb did not directly affect the T cell functions was further confirmed by stimulating purified T cells from aldicarb-treated mice with phorbol myristate acetate and calcium ionophore, a response which is independent of the accessory cells and which was found to be normal in aldicarb-treated mice. It was observed that the macrophages from aldicarb-treated mice demonstrated a decreased capacity to stimulate conalbumin-specific T helper cell clone, D10.G4, and when activated produced decreased amounts of IL-1 when compared to control macrophages. Also, the decreased stimulation of D10.G4 clone by aldicarb-treated macrophages was reconstituted when exogenous recombinant IL-1 was added to the cultures. These data together suggested that aldicarb affects the macrophage functions by interfering with IL-1 production and that it does not affect the T cell functions directly. PMID- 2260090 TI - TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, inducing cleft palate and hydronephrosis at doses which are not overtly maternally toxic or embryotoxic. After TCDD exposure the palatal shelves of normal size come into contact, but fail to fuse due to altered differentiation of the medial epithelial cells. These cells continue to express EGF receptors, proliferate, and differentiate into an oral-like stratified squamous epithelium. The present study examines the effect of TCDD on the expression of growth factors which are believed to regulate differentiation and proliferation in the palate. This study also examined the combined effect of TCDD and retinoic acid (RA), since in teratology studies coadministration of these agents results in an enhancement of cleft palate incidence. Embryos were exposed in vivo on Gestation Day (GD) 10 or 12 to TCDD ot TCDD + RA and the palatal shelves were dissected on GD 14-16. Growth factor expression was determined immunohistochemically using antibodies to TGF-alpha, EGF, TGF-beta 1, or TGF-beta 2. The growth factors displayed specific spatial and temporal expression in the palatal shelves. TCDD reduced the expression of TGF-alpha, EGF, and TGF-beta 1 in epithelial and mesenchymal cells. The degree of reduction was generally greater after exposure on GD 10 to TCDD alone or in combination with RA when compared to that on GD 12. The abnormal proliferation and differentiation of TCDD-exposed medial cells may be a response to reduced expression of EGF and TGF-alpha. Low levels of these factors may be related to the previously observed elevated levels of EGF receptors in medial cells. In other systems, low levels of ligand have resulted in upregulation of the EGF receptor. Continued proliferation and altered differentiation could also be attributable to decreased levels of TGF-beta 1, a factor inhibitory to epithelial proliferation. Since TGF-beta 1 stimulates mesenchymal growth and TGF alpha and EGF stimulate epithelial proliferation, the formation of small shelves after exposure to TCDD + RA on GD 10 may be due to the severe reduction in these factors. Only a slight to moderate reduction in growth factor expression occurs after exposure to TCDD + RA on GD 12 and in this case shelves of normal size form. Since TCDD and RA appear to act in part through pathways that involve TGF beta 1, in vitro experiments were designed to examine the involvement of TGF-beta 1 in TCDD teratogenicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2260091 TI - A physiologically based toxicokinetic model for the uptake and disposition of waterborne organic chemicals in fish. AB - A physiologically based toxicokinetic model was developed to predict the uptake and disposition of waterborne organic chemicals in fish. The model consists of a set of mass-balance differential equations which describe the time course of chemical concentration within each of five tissue compartments: liver, kidney, fat, and richly perfused and poorly perfused tissue. Model compartmentalization and blood perfusion relationships were designed to reflect the physiology of fishes. Chemical uptake and elimination at the gills were modeled as countercurrent exchange processes, limited by the chemical capacity of blood and water flows. The model was evaluated by exposing rainbow trout (Oncorhynchus mykiss) to pentachloroethane (PCE) in water in fish respirometer-metabolism chambers. Exposure to 1500, 150, or 15 micrograms PCE/liter for 48 hr resulted in corresponding changes in the magnitude of blood concentrations without any change in uptake kinetics. The extraction efficiency for the chemical from water decreased throughout each exposure, declining from 65 to 20% in 48 hr. Extraction efficiency was close to 0% in fish exposed to PCE to near steady state (264 hr), suggesting that very little PCE was eliminated by metabolism or other extrabranchial routes. Parameterized for trout with physiological information from the literature and chemical partitioning estimates obtained in vitro, the model accurately predicted the accumulation of PCE in blood and tissues, and its extraction from inspired water. These results demonstrate the potential utility of this model for use in aquatic toxicology and environmental risk assessment. PMID- 2260092 TI - Ethanol decreases cadmium hepatotoxicity in rats: possible role of hepatic metallothionein induction. AB - The present investigation examines the possibility that Cd and ethanol have a significant toxicological interaction. This examination was warranted as exposure to either chemical is known to compromise human health. Inasmuch as both chemicals affect the morphology, biochemistry, and physiology of liver, it seemed reasonable to consider liver as a possible site of interaction. Specifically, the hypothesis that ethanol alters the hepatotoxic action of Cd was evaluated. Accordingly, male rats were injected iv with hepatotoxic (3.0 mg/kg) or lethal (4.5 mg/kg) dosages of Cd, 24 hr after single-dose ethanol administration (7 g/kg, po). Cd-induced hepatotoxicity was assessed by measuring the activities of alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase in serum collected 10 hr after Cd injection. Lethality was assessed by recording the number of survivors over a 7-day period. Prior exposure to ethanol substantially reduced the lethal and hepatotoxic properties of Cd. Two mechanisms were evaluated in an effort to explain ethanol-induced suppression of Cd hepatotoxicity. Ethanol pretreatment was postulated to: (1) enhance Cd excretion in bile thereby decreasing hepatic Cd content and/or (2) reduce the interaction between Cd and target sites in liver such as organelles and cytosolic high molecular-weight (HMW) proteins. The first proposed mechanism was incorrect as the biliary excretion of Cd was nearly abolished and the concentration of Cd in whole liver increased (33%) as a result of ethanol exposure. The second proposed mechanism was a plausible explanation of ethanol-induced suppression of Cd hepatotoxicity because ethanol pretreatment decreased (approximately 60%) the content of Cd in nuclei, mitochondria, and endoplasmic reticulum, and nearly eliminated the association of Cd with cytosolic HMW proteins. Reduction in the concentration of Cd in potential target sites of intoxication was caused by a metallothionein-promoted sequestration of Cd in cytosol. PMID- 2260093 TI - The effect of NO2 exposure on perfusate distribution in isolated rat lungs: pulmonary versus bronchial circulation. AB - Isolated rat lung (IPL) studies have suggested that the pulmonary uptake of inhaled nitrogen dioxide (NO2) is governed via a chemical reaction-dependent process which results in NO2-derived reaction products diffusing into the vascular space. Experimental results indicated that substantial proportions of this reactive absorption occur in distal sites. However, gas phase deposition in proximal locations cannot be ruled out due to the lack of information on bronchial perfusion in rat IPL preparations. Consequently, we evaluated the presence of pulmonary-to-bronchial anastomotic perfusate flow in control and NO2 exposed (10.3 ppm) rat IPL. Monastral blue (MB) was used as a vascular marker and was infused into the pulmonary artery catheter either for recirculation at time zero or as an end-experiment (60 min) bolus. In addition, MB was infused into control in situ preparations to observe intact bronchial circulations. Lungs were prepared for routine evaluation by light microscopy. In situ MB was observed in all pulmonary and bronchial vessels. In IPL, MB was observed only in far terminal airway-associated vessels. No differences were observed in MB distribution between bolus (end-experiment) and recirculated (time zero) applications. NO2 exposure produced no effect on MB distribution. We conclude that in rat IPL: (1) negligible anastomotic flow occurs from the pulmonary into the bronchial circulation, (2) nonedemagenic NO2 exposures do not alter existing perfusate distribution, and (3) the perfusate appearance of inhalation-derived species results from gas phase deposition only in distal sites which have ready accessibility to the pulmonary circulation. PMID- 2260094 TI - Alteration in protein synthesis in primary cultures of rat kidney proximal tubule epithelial cells by exposure to gallium, indium, and arsenite. AB - Patterns of protein synthesis in primary cultures of rat kidney proximal epithelial tubule cells were examined following exposure to gallium (Ga) chloride, indium (In) chloride, and sodium arsenite. After incubation with these chemicals for 20 hr, newly synthesized proteins were labeled with [35S]methionine. 35S-labeled proteins in the cells were separated by SDS/polyacrylamide gel and two-dimensional gel electrophoresis and detected by fluorography. A protein with molecular weight (Mr) of 30,000 was markedly induced by exposure to 300 microM Ga or 10 microM arsenite, and synthesis of proteins with Mr of 85,000, 71,000, 65,000, 51,000, 38,000, and 28,000 was also increased by Ga or arsenite. Arsenite exposure increased synthesis of eight different proteins, which were not induced by Ga. No significant changes in protein synthesis were observed with 300 microM In exposure. Release of lactate dehydrogenase from the cells was not significantly increased by exposure to concentrations of 300 microM Ga and 3 microM arsenite or less. In the absence of overt cell injury, the induction of these proteins may be useful as an early indicator for assessing exposure to Ga. PMID- 2260095 TI - Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters. AB - Our previous study showed that pretreatment with buthionine sulfoximine (BSO), which inhibits glutathione synthesis, results in acute renal failure with oliguria in hamsters ingesting sodium arsenite (5 mg As/kg). For a deeper understanding of the relationship between arsenic metabolism and the subsequent development of nephrotoxicity, we studied excretion, tissue retention, biotransformation, pharmacokinetics, and histopathological events in the kidneys of hamsters both with and without BSO pretreatment. The total amount of arsenic excreted in the urine and feces within 72 hr of arsenite administration was more than fivefold lower in BSO-pretreated animals than in the controls without pretreatment (9.2 versus 53.4% of the arsenic dose). The persistence of high amounts of total arsenic was apparent in the blood, liver, and kidneys of BSO pretreated hamsters, even though the content of inorganic arsenic steadily decreased with time. The disappearance of inorganic arsenic from the blood showed a biphasic elimination pattern characterized first by a rapid component with a half-life of 4.5 hr and second by a slower component with a half-life of 58.0 hr in the BSO-pretreated hamsters, while these half-lives were 0.6 and 11.0 hr, respectively, in the controls. BSO pretreatment not only impaired the excretion of inorganic arsenic, but also impaired its methylation. Combined BSO/arsenite treatment resulted in renal tubular necrosis which was prominent at 1 hr after arsenite administration. By 1 hr, the renal content of inorganic arsenic in the BSO-pretreated animals was 1.7 times higher than that in the controls. This study demonstrates that glutathione depletion elicits the nephrotoxic manifestations of arsenic poisoning. PMID- 2260096 TI - Toxicological studies on a benzofurane derivative. II. Demonstration of peroxisome proliferation in rat liver. AB - The uricosuric drug benzbromarone (3,5-dibromo-4-hydroxyphenyl)-1-(2-ethyl-3 benzofuranyl)methanone, a benzofurane derivative, was studied for its effects on parameters related to hepatic peroxisome proliferation. Groups of male F-344 rats were fed either basal diet, the peroxisome proliferator clofibrate at 5000 ppm as a comparison compound, or benzbromarone at two doses, 1000 and 2000 ppm. Benzbromarone and clofibrate produced hepatomegaly and increases in the activities of catalase, acyl CoA oxidase, malate dehydrogenase, and glycerol-3 phosphate dehydrogenase. Benzbromarone and clofibrate also both induced similar histologic and ultrastructural changes in hepatocytes, including induction of peroxisomes. Therefore, benzbromarone acted as a peroxisome-proliferating agent in rats under these conditions. Benzbromarone differs from other peroxisome proliferators in its chemical structure, uricosuric action, and the morphology of liver peroxisomes that were induced by exposure. PMID- 2260097 TI - Toxicological studies on a benzofuran derivative. III. Comparison of peroxisome proliferation in rat and human hepatocytes in primary culture. AB - Primary cultures of rat and human hepatocytes were used in our in vitro studies for investigating species differences in the response to a peroxisome proliferating benzofuran derivative, benzbromarone. Cyanide-insensitive palmitoyl coenzyme A oxidation (a marker of peroxisome fatty acid beta-oxidation) and electron microscopy were used to assess peroxisome proliferation. Hepatocytes were cultured essentially as described by Mitchell et al. (1984, Arch. Toxicol. 55, 239-246); clofibric acid and mono(2-ethylhexyl) phthalate (MEHP) were used as reference compounds, as they are well known to cause peroxisome proliferation in rat hepatocytes in primary culture. The benzofuran derivative, tested at drug concentrations ranging from 2.37 to 59.20 microM in rat hepatocyte primary cultures, induced, after 96 hr, a dose-related increase of the peroxisomal beta oxidase activity correlated with an increased number of peroxisomes; this increase was much less marked than that obtained with clofibric acid or MEHP. By contrast, using the same range of concentrations, human hepatocytes in primary culture treated with benzbromarone revealed no enhancement of enzymatic activity and no concomitant statistically significant increase in the number of peroxisomes; the same observations were reported with clofibric acid and MEHP. These results demonstrate clearly that species differences in sensitivity to peroxisome proliferation with the benzofuran derivative do exist. PMID- 2260098 TI - Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8 tetrachlorodibenzo-p-dioxin-treated rats. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces a delayed onset hypergastrinemia in rats. The purpose of the present study was to determine if the increased serum gastrin concentrations were caused by decreased gastric acid secretion, decreased plasma clearance of gastrin, and/or decreased gastric emptying. It was found that TCDD treatment decreased gastric acid secretion as determined by decreases in gastric secretory volume, acidity, and total acid output in pylorus-ligated rats. Also, both dose-response and time-course curves for decreased gastric acid secretion in TCDD-treated rats were similar to those for hypergastrinemia. These findings, as well as a significant inverse correlation between serum gastrin concentrations and total gastric acid output in rats treated with graded doses of TCDD (5-100 micrograms/kg), suggest that TCDD induced decreases in gastric acid production cause elevated serum gastrin concentrations. Neither hypergastrinemia nor decreased gastric acid secretion were observed in pair-fed control rats, demonstrating that neither effect was secondary to undernutrition. The TCDD-induced decrease in gastric acid secretion was not caused by a decrease in the number of acid-secreting parietal cells in the stomach, but rather was associated with a decrease in parietal cell responsiveness to gastrin-elicited acid secretion. This was evidenced by both elevated serum gastrin concentrations and a pharmacological dose of pentagastrin failing to stimulate gastric acid secretion in TCDD-treated rats. The disappearance of iv-administered gastrin-17 from the serum was not affected by TCDD treatment, suggesting that reduced serum gastrin clearance is not responsible for the TCDD-induced hypergastrinemia. Although a marked decrease in gastric emptying of a 51Cr-labeled liquid test meal was also observed in TCDD treated rats, the lowest dose of TCDD required to produce this effect was greater than that needed to cause hypergastrinemia. This suggests that the hypergastrinemic effect of TCDD is not secondary to a decrease in gastric emptying. We conclude that the most probable cause of hypergastrinemia in TCDD treated rats is decreased gastric acid secretion. PMID- 2260099 TI - Echocardiographic and radionuclide angiographic observations following scorpion envenomation by Leiurus quinquestriatus. AB - The echocardiographic and radionuclide angiographic abnormalities in children after scorpion envenomation with L. quinquestriatus, were evaluated. Five children were severely hypertensive, one of them in respiratory failure and another had pulmonary edema. The results revealed poor global contractility 12-15 hr after the sting in three patients. The radionuclide angiograms also revealed poor contractility with low ejection fraction. There was enzymatic evidence of myocardial damage. The changes observed in the echocardiograms and radionuclide angiograms were attributed to catecholamine induced myocardial ischemia. The abnormalities observed suggest that systolic dysfunction plays a role in the pathogenesis of heart failure in scorpion envenomation, in addition to a decrease of left ventricular compliance and increased impedance to left ventricular emptying. The beneficial effects of nifedipine in hypertension and other cardiovascular manifestations justify the routine use of afterload reduction in children with cardiovascular manifestations after scorpion envenomation. PMID- 2260100 TI - Isolation and characterization of toxic proteins from the venom of the Venezuelan scorpion Tityus discrepans (Karsch). AB - Four toxic, electrophoretically homogeneous proteins were isolated by ion exchange chromatography on CM-cellulose-52 from the venom of the scorpion Tityus discrepans (range North Central Venezuela), named TdIV, TdV, TdVIII and TdIX. Component TdVIII, with 56 amino acid residues and mol. wt 6140 was the most toxic by i.p. injections into mice and had an intracisternal LD50 of 7.9 micrograms protein/kg body weight. Amino acid compositions of components TdIV and TdV were very similar, suggesting that they could be highly homologous proteins, although presumably contaminated one by the other. A fifth component, named TdIII, non toxic by i.p. injections, was also isolated in homogeneous form. The i.v. and intracisternal LD50 values of the whole T. discrepans venom were 2.5 mg/kg and 16.0 micrograms/kg, respectively. PMID- 2260101 TI - Purification and some properties of a hemolysin from the poisonous mushroom Rhodophyllus rhodopolius. AB - A hemolytic protein which causes diarrhea and death to mice was purified from the fruit bodies of a poisonous mushroom species Rhodophyllus rhodopolius (Fries) by DEAE-cellulose column chromatography, ammonium sulfate precipitation, gel filtration on Sephadex G-200, and DEAE-Sephadex A-25 column chromatography. The mol. wt of the purified hemolysin was estimated to be 40,000 by SDS polyacrylamide slab gel electrophoresis. The hemolytic activity of the purified hemolysin was destroyed by heating at 60 degrees C for 10 min, and partially reduced by pepsin, papain and 2-mercaptoethanol. Cholesterol and phosphatidylcholine did not inhibit the activity. The hemolysin was unstable below pH 7.0 but stable at pH 8.0. The optimal pH for hemolysis was 6.0. Hemolysis did not occur below 4 degrees C even though the hemolysin bound to the erythrocyte. Mouse, chicken, rat, horse and human erythrocytes were sensitive in this order, but sheep and cow erythrocytes were not lysed by the toxin. PMID- 2260102 TI - The action of notexin from tiger snake venom (Notechis scutatus scutatus) on acetylcholine release and compartmentation in synaptosomes from electric organ of Torpedo marmorata. AB - At rest, in the presence of calcium, notexin induced a rapid and concentration dependent leakage of acetylcholine from nerve endings. In the presence of 20 nM notexin (5 min), synaptosomes were well-preserved structurally and they responded to addition of A23187 ionophore by a normal calcium-dependent acetylcholine release. When stimulated by high-K+ depolarization, evoked acetylcholine release was increased when notexin was present. These findings demonstrate that notexin (up to 100 nM) does not inhibit the acetylcholine release process itself. Further studies on intracellular acetylcholine compartmentation showed that, in the presence of calcium, nm concentrations of notexin were able to mobilize vesicular acetylcholine, the amount of which strongly decreased and fed the cytoplasmic compartment leading to an important redistribution of the neurotransmitter. Other metabolic studies under notexin confirmed the inhibition of the synaptosomal membrane choline transport, but failed to elicit changes in the choline acetyltransferase activity. In order to distinguish between the phospholipase A2 activity of notexin and its neurotoxic effects, we compared effects of notexin to those obtained with a non-neurotoxic pancreatic phospholipase A2. The latter exhibits similar effects but at a higher range of concentration than notexin. PMID- 2260103 TI - Enzyme-linked immunosorbent assay for the detection of Bothrops jararaca venom. AB - This study reports an enzyme-linked immunosorbent assay for detecting Bothrops jararaca venom in fluids, employing the sandwich method with biotin/avidin amplification. The assay exhibits high accuracy in correlating optical densities with venom concentrations (r = 0.98), high reproducibility, low background and limited cross-reactivity with venom from other snake genera. Nevertheless, it was unable to distinguish among venoms from different bothropic species. Using this method we evaluated the serum kinetics of Bothrops jararaca venom in C57BL/6 mice. High concentrations were found in serum just 15 min after injection (151 +/ 41 ng/ml; mean +/- S.D.), followed by a progressive fall (102 +/- 46, 74 +/- 39 and 50 +/- 22 ng/ml after 1, 3 and 6 hr respectively), being undetectable by 24 hr. Such serum kinetics indicates a pattern of a rapid absorption of venom from the inoculation site, followed by a slow and progressive drop in its serum levels. This ELISA was a reliable tool in the determination of Bothrops jararaca venom levels in mouse serum, and may become useful in other fields of bothropic venom research. PMID- 2260104 TI - Structure of the toxin isolated from carp (Cyprinus carpio) bile. AB - Attempts were made to elucidate the structure of the toxin isolated from the bile of carp Cyprinus carpio, which is possibly responsible for carp poisoning. By fast atom bombardment (FAB) mass spectrometry, along with 1H- and 13C-NMR, a molecular formula of C27H48O8S containing a sulfate ester group was deduced. Those and other analytical data allowed us to conclude the structure of carp toxin to be 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 26, 27-pentol 26 sulfate, which agreed essentially with that of 5 alpha-cyprinol, an alcohol specific to carp bile, in which the sulfate ester at the C-26 position is lacking. PMID- 2260105 TI - Tetanus antitoxin binds to intracellular tetanus toxin in permeabilized chromaffin cells without restoring Ca2(+)-induced exocytosis. AB - Tetanus toxin blocks Ca2(+)-evoked catecholamine release from permeabilized bovine adrenal chromaffin cells preloaded with gangliosides. Tetanus toxin preincubated with its specific antibodies F(ab')2 is without any effect on exocytosis. Specific antitetanus F(ab')2 presented to chromaffin cells which are pretreated with tetanus toxin and permeabilized by digitonin cannot restore exocytosis. Under the same conditions, however, 125I-labeled F(ab')2 accumulates in chromaffin cells. The accumulation depends on the presence and concentration of tetanus toxin and can be prevented by an excess of unlabeled F(ab')2. Once tetanus toxin has initiated block of exocytosis, it cannot be neutralized by binding to its specific antibody. PMID- 2260106 TI - Tetrodotoxin and related substances in a ribbon worm Cephalothrix linearis (Nemertean). AB - A ribbon worm Cephalothrix linearis (Nemertean) showed a high toxicity, of up to 22,000 MU/g proboscis and 13,600 MU/g body, in terms of tetrodotoxin. This organism secreted the toxin from the skin when wiped with gauze. The toxin was partially purified from the secretion as well as the wiped body by ultrafiltration and Bio-Gel P-2 column chromatography. Thin-layer chromatographic, electrophoretic, high performance liquid chromatographic, and gas chromatography-mass spectrometric analyses showed that the secreted toxin was composed almost exclusively of a tetrodonic acidic-like substance, whereas the remaining toxin in the wiped body consisted of the said substance and tetrodotoxin. PMID- 2260107 TI - Histopathological studies on experimental marine toxin poisoning--5. The effects in mice of yessotoxin isolated from Patinopecten yessoensis and of a desulfated derivative. AB - The histopathological response of male ICR mice to yessotoxin, isolated from the digestive organ of scallops Patinopecten yessoensis, was compared with that of desulfated yessotoxin. The target organ of the former was the heart and those of the latter were the liver and pancreas. Electron microscopically, marked intracytoplasmic edema in cardiac muscle cells was seen within 3 hr after the i.p. injection of over 300 micrograms/kg of yessotoxin. In contrast, desulfated yessotoxin at the same dose caused within 24 hr of i.p. injection severe fatty degeneration and intracellular necrosis in the liver and pancreas but not in the heart. Biochemically, the content of triglycerides in the liver of mice treated with desulfated yessotoxin increased about 60 times, and phospholipids two-fold more than the control levels of those of mice treated with yessotoxin. PMID- 2260108 TI - Florida red-tide toxins (brevetoxins) produce depolarization of airway smooth muscle. AB - Crude preparations of brevetoxin (PBTX) produce airway contraction; however, it is not known if this toxin-induced mechanical response is coupled to changes in airway smooth muscle membrane potential. Membrane potentials and contractility of in vitro canine trachealis smooth muscle preparations were simultaneously measured with a microelectrode and microforce transducer before and during exposure to either the crude toxin (0.01-1.2 micrograms/ml), or the purified fractions PBTX-2 or PBTX-3 (0.01-0.07 micrograms/ml). Membrane potentials in cultured airway smooth muscle-reaggregate preparations were similarly studied. Toxins produced concentration-dependent depolarizations and contractions in in vitro preparations. These responses were not obtained in the presence of either the muscarinic blocking agent atropine, the sodium channel blocker tetrodotoxin (TTX), 0 mM extracellular Ca2+, or the Ca2+ channel blocker verapamil. The toxins were without effect in cultured cells, whereas acetylcholine produced depolarizations which were blocked in the presence of atropine, but not TTX. This suggested the presence of functional cholinergic receptors in cultured cells, and the PBTX-induced release of endogenous acetylcholine from peripheral nerve endings in the in vitro airway smooth muscle response. PMID- 2260109 TI - Presence of saxitoxin in toxic extracts from Gonyaulax polyedra. AB - A "red tide" bloom of Gonyaulax polyedra occurred in Italy in Autumn, 1988. Algal concentrated extracts and undiluted water samples from the bloom were tested both with the Microtox system and a mouse bioassay, revealing the presence of paralytic shellfish poison-like neurotoxins. Saxitoxin levels evaluated on the basis of toxicological and instrumental analysis showed discrepancies. Other toxins could be present in addition to paralytic shellfish poison. PMID- 2260110 TI - Comparison of venom constituents from four tiger snake (Notechis) subspecies. AB - Venoms from Notechis scutatus scutatus, Notechis ater serventyi, Notechis ater humphreysi and Notechis ater ater were compared using gel filtration, polyacrylamide gel electrophoresis, and western blotting. All venoms gave slightly different elution profiles on a Superose 12 gel filtration column. When examined by SDS-PAGE and western blotting, all venoms appeared to have notexin like proteins except for N. a. serventyi. N. a. serventyi lacked proteins migrating in the notexin molecular weight range, showed no reactivity toward a monoclonal antibody that reacted strongly with notexin in western blot analysis, and had twice the LD50-value of the other three venoms. PMID- 2260111 TI - Effects of ochratoxins A and B on prechondrogenic mesenchymal cells from chick embryo limb buds. AB - Prechondrogenic mesenchymal cells from the limb buds of 4-day chick embryos were cultured together with either ochratoxin A (OA) or ochratoxin B (OB) for 6 days. Both toxins inhibited the accumulation of cartilage proteoglycans and general protein synthesis in a concentration-related manner. The IC50 was 1.9 microM for OA and 6.2 microM for OB. Incubating the micromass with OA for periods ranging from 2 h up to 6 days did not produce any metabolites, indicating that OA was the proximal toxic compound in these studies. Neither preincubation with OB nor simultaneous exposure to non-toxic concentrations of OB together with various concentrations of OA influenced the toxicity of OA. The data indicate that interference of OA with general protein synthesis, both in vivo and in vitro, is an important mechanism underlying OA-induced embryotoxicity. PMID- 2260112 TI - Effects of acetone administration on drug-metabolizing enzymes in mice: presence of a high-affinity diethylnitrosamine de-ethylase. AB - Treatment of CD1 mice with acetone raised activities of hepatic microsomal p nitrophenol hydroxylase, ethoxycoumarin de-ethylase, acetone hydroxylase and diethylnitrosamine de-ethylase (DENd) several-fold. P-450IIE1-linked acetone hydroxylase showed the highest inducibility. In microsomes from acetone pretreated mice the cytochrome b5 and P-450 content was nearly doubled and their electrophoretic profile showed induction of a protein of Mr 53,000, probably P 450IIE1. Liver phase II enzymes were not affected by acetone treatment. Kinetic analyses of DENd were performed in control or acetone-induced microsomes and Km and Vmax were determined. Two distinctly apparent Km values (0.56 and 20.3 mM) were observed for DENd of control microsomes and at least 3 apparent Km values (0.05, 0.51, 8.4 mM) were observed in acetone-induced microsomes. Thus, acetone administration to mice induces a high-affinity form of DENd which can be important in vivo at low diethylnitrosamine (DEN) exposure as this enzyme functions when DEN concentration is below 0.1 mM. PMID- 2260113 TI - Subacute inhalation toxicity study of an ice-nucleation-active Pseudomonas syringae administered as a respirable aerosol to rats. AB - The inhalation toxicity of a commercial sample of an ice-nucleation-active Pseudomonas syringae (strain 31a) was evaluated by repetitively exposing rats to about 700 mg/m3 of an aerosol consisting of a suspension of 0.0008, 0.4 or 0.8 g/l of bacteria in water for 2 h per day, 5 days per week for 13-14 exposures. No mortality, moribundity or biologically significant differences in clinical signs, body weight, food consumption or clinical pathology were observed. Animals tested at 500 times (0.4 g/l) and 1000 times (0.8 g/l) the recommended ice-nucleation concentration (0.0008 g/l) exhibited concentration-dependent increased lung weights. Several animals exhibited enlarged tracheobronchial lymph nodes. The pulmonary responses observed are considered compatible with a mild irritant reaction. There was no evidence of bacterial infection. Animals tested at a concentration typical for the discharge mouth of a snow gun (0.0008 g/l) demonstrated no significant biological effect. PMID- 2260114 TI - Usefulness of MC-540 fluorescent dye as probe versus scanning electron microscopy for assessing membrane changes. AB - The effect of primaquine enantiomers on cell membranes of glucose-6-phosphate (G 6PD)-deficient erythrocytes was studied in vitro. Staining with merocyanine (Mc 540) showed that exposure to primaquine enantiomers produces significant fluorescence in G-6PD-deficient erythrocytes, indicating marked drug-induced alterations in membrane fluidity. Scanning electron microscopy (SEM) studies confirmed that primaquine enantiomers altered membrane morphology (by producing stomatocytes) in both normal and G-6PD-deficient cells. The concentration dependent effect, however, was more pronounced with MC-540, a lipophylic dye, than with SEM (an expensive technique). PMID- 2260115 TI - The effects of low levels of dietary toxic weed seeds (jimson weed, Datura stramonium and sicklepod, Cassia obtusifolia) on the relative size of rat liver and levels and function of cytochrome P-450. AB - Preliminary studies and previous work by other investigators have shown that jimsonweed and sicklepod seeds are very toxic. Such seeds and others are co harvested and are often found mingling with commercial grain destined for human consumption. Low levels of these seeds were studied here to determine whether such levels would show signs of intoxication in rats by modulating growth, liver weight and relative size, cytochrome P-450 levels and function, and other relevant parameters proven to be sensitive to low levels of toxicants. Assessment of these factors showed that jimson weed does give indications of intoxication at low levels, whereas the highly toxic sicklepod does not give discernible indications. PMID- 2260116 TI - Effect of almond and anis oils on mouse liver alcohol dehydrogenase, aldehyde dehydrogenase and heart lactate dehydrogenase isoenzymes. AB - The effects of short-term intraperitoneal injection of diluted almond or anis oil on heart lactate dehydrogenase isoenzymes, liver alcohol dehydrogenase and subcellular aldehyde dehydrogenase were studied in the female mouse. Hepatic alcohol dehydrogenase was induced from control by administration of almond oil 3.2 g/kg/d for 7 days, or anis oil 1.6 g/kg/d for 7 days. Treatment with almond but not anis oil inhibited both cytoplasmic and mitochondrial liver aldehyde dehydrogenase. The mitochondrial isoenzyme with an apparently low Km was also inhibited by the almond oil trial. No significant changes occurred in heart lactate dehydrogenase isoenzymes by the treatments used. The enzymatic inhibition kinetics were found to be non-competitive. The apparent Km for almond-treated mouse aldehyde dehydrogenase was greater than the controls. This indicates lower substrate affinity for almond oil than for acetaldehyde. The results suggest adverse hepatic metabolic interaction between almond oil and alcohol. PMID- 2260117 TI - Induction of gastric mucosal cell proliferation by the fungicide captan: role of tyrosine kinases. AB - Captan (1,2,3,6-tetrahydro-N-trichloromethylthiophthalmide), a widely used fungicide, has been shown to induce carcinoma in the gastrointestinal tract of rodents. However, little is known about the captan induction of early biochemical changes in the gastrointestinal tract. The present investigation examines the changes in gastric mucosal proliferative activity in 2-month-old Fischer 344 rats following a daily injection (s.c.) of captan (100 mg/kg body wt.) in DMSO while being infused (osmotic minipump) with the same compound (7.14 mg captan/kg body wt./h) for 2 weeks. The control rats received the vehicle the same way. The change in proliferative activity was related to tyrosine kinase (Tyr-k) activity and tyrosine-specific phosphorylation of protein(s) in gastric mucosal membranes since these intracellular events are thought to play an important role in proliferation, differentiation and transformation of cells. After 2 weeks of captan administration gastric mucosal DNA synthesis and thymidine kinase activity (indicators of proliferative activity) were increased by 330% (P less than 0.025) and 98% (P less than 0.025), respectively, when compared with the corresponding controls. Gastric mucosal DNA content was also increased by 90% (P less than 0.025) after administration of captan. These increases were associated with about 3-fold rise in Tyr-k activity and 2-fold increase in tyrosine phosphorylation of 6 mucosal membrane proteins with Mr of 105, 90, 60, 55, 48 and 37 kDa. We conclude that captan stimulates gastric mucosal cell proliferation, and activation of Tyr-k and tyrosine phosphorylation of certain membrane proteins may be important in the regulation of this process. PMID- 2260118 TI - Effect of cadmium on blood glucose level in the rat. AB - The purpose of this study was to determine the effect of cadmium (Cd) or Cd and selenium (Se) administered simultaneously on plasma glucose level. Male Sprague Dawley derived rats (180-300 g), maintained under controlled environmental conditions, were segregated into fed and 24-h fasted groups prior to experimentation. Each group consisted of 3 subgroups which received one of the following treatments intraperitoneally: sodium acetate (NaAc) (1.23 mg/kg), Cd (0.84 mg/kg) or a combination of Se and Cd (1.6 and 0.84 mg/kg respectively). Plasma glucose was measured before and 30, 60, 120, 180, 240, 300 or 360 min after treatment. Results indicate that both Cd and concurrent administration of Se and Cd induce hyperglycemia in fed and fasted rats. PMID- 2260119 TI - Tolerance to lead-induced porphyrin metabolic disorders following lead pretreatment in mice. AB - The protective effect of pretreatment with lead on lead-induced toxicity was investigated in mice, using some biological parameters such as urinary excretion of delta-aminolevulinic acid (ALA) and coproporphyrin, accumulation of erythrocyte protoporphyrin and inhibition of erythrocyte delta-aminolevulinic acid dehydratase; these are useful indicators for evaluating the effects on health of lead. It was demonstrated that pretreatment with a single intraperitoneal dose of 2 mg Pb/kg, 7 days prior to the challenge dose, prevents in part the increasing excretion of urinary ALA induced by a challenge exposure to lead (200 ppm) in the drinking water for 7 days. PMID- 2260120 TI - No change in serum dopamine-beta-hydroxylase activity in workers exposed to trichloroethylene. AB - To determine whether occupational exposure to trichloroethylene (TCE) influences sympathetic nerve activity, serum dopamine-beta-hydroxylase (DBH) activities were analyzed in 84 male workers exposed to TCE and 83 male age-matched controls. The workers were exposed to about 22 ppm TCE in air. There were no significant differences between the mean serum DBH activity levels for the exposed workers and the corresponding controls. No significant correlation was found between the serum DBH activities and the urinary TCE-metabolite levels or the duration of employment of the workers. The results suggest that chronic occupational exposure to TCE did not influence sympathetic nerve activity of the workers. PMID- 2260121 TI - Structural influences on intracellular cadmium mobilization by dithiols. AB - An examination of 5 dithiols, N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), benzene-1,2-dithiol (BDT), toluene-3,4-dithiol (TDT), alpha, alpha'-dimercapto-o xylene (DOX), and 4,5-dimethyl-alpha,alpha'-dimercapto-o-xylene (DDOX), reveals that these compounds are all inferior to previously reported compounds as agents for the in vivo mobilization of cadmium from its intracellular sites, although all possess sulfhydryl groups capable of reacting with cadmium. The results demonstrate the considerable importance of those parts of the molecule which do not participate directly in the formation of chelate rings in the determination of the ultimate behavior of such compounds in vivo. PMID- 2260122 TI - Memory deficits in workers suffering from hard metal disease. AB - This study examined memory functioning on the Wechsler Memory Scale-Revised in a group of adult tungsten carbide workers with hard metal disease and a group of matched controls. The hard-metal-exposed group of workers showed memory deficits related to difficulties in attention and verbal memory, with an apparent sparing of visual-spatial memory. Implications of this finding for future research are discussed. PMID- 2260123 TI - Use of fetal mouse salivary glands in culture to detect embryotoxicity: evaluation of eight additional chemicals. AB - Several developmental processes interact to convert an epithelial bud into a gland with many lobes. For each chemical tested, 20 glands were placed into a control and each of 3 concentrations of the chemical. From dose-response curves, the concentration that reduced gland growth by 50% was determined and divided into the LD50 for mice. These ratios were used to compare the toxicity of the chemicals. The ratios of cyclamate, diphenhydramine, allopurinol, nitrofen and urethane would indicate that embryotoxicity would not be expected without maternal toxicity. Promethazine, diethyldithiocarbamate, and 5-fluorouracil would be expected to show embryotoxicity without maternal toxicity. PMID- 2260124 TI - Cyclosporin A--a chemoprotectant against microcystin-LR toxicity. AB - Microcystin-LR (MCLR) is a potent hepatotoxin that rapidly produces death in experimental animals. We have shown that cyclosporin A (CsA) can prevent the toxic and lethal effects of MCLR in mice. The LD50 of MCLR in mice is approximately 61 micrograms/kg, and 100 micrograms/kg produces death in 100% of treated mice. The minimum dose of CsA which prevented lethality in mice given 100 micrograms MCLR/kg i.p. was 10 mg/kg. This dose of CsA did not protect mice against higher doses of MCLR. Survival of all mice given 100 micrograms MCLR/kg was achieved if 10 mg CsA/kg was given 0.5-3 h prior to the MCLR but not if the CsA was co-administered or given after the MCLR. The results indicate that CsA effectively protects mice against a lethal dose of MCLR, but that the time of administration and the dose of CsA are critical determinants of the chemoprotective effects. PMID- 2260125 TI - Elevated blood glucose is associated with poor outcome in the carbon-monoxide poisoned rat. AB - Levine-prepared, unanesthetized rats exposed to 2400 and 2700 ppm carbon monoxide (CO) for 90 min were used to examine the effect of acute CO poisoning on plasma glucose and insulin concentrations, and neurologic dysfunction. Body temperature and mean arterial blood pressure fell progressively during CO exposure. Glucose rose during initial CO exposure, then declined: glucose increased again after 2 h of room air recovery. Neurologic deficit, behaviorally-assessed after 4 h of recovery, was strongly correlated (r = 0.71, P less than 0.001) with glucose increase during the first 2 h of recovery. Recovery hyperglycemia was, in turn, correlated (r = 0.69, P less than 0.001) with the fall in glucose during the second half of CO exposure. Neurologic deficit was also correlated, but less strongly so, with hypoglycemia during CO exposure. Failure to rapidly regain body temperature during recovery was correlated with the post-CO rise in glucose concentration and with increased neurologic deficit. Plasma insulin activity was depressed immediately following CO exposure, and increased during recovery. CO induced hypothermia was greater at 2700 than at 2400 ppm CO, as were post-CO recovery hyperglycemia, neurologic deficit and mortality, while body temperature recovery was less complete. The results provide evidence of an association between neurologic deficit and general morbidity following acute CO poisoning and the magnitude of post-CO hyperglycemia. PMID- 2260126 TI - Phototoxic potential of quinolone antibacterial agents in Balb/c mice. AB - The phototoxic potentials of quinolone antibacterial agents were investigated in Balb/c strain mice. The mice were orally administered nalidixic acid (NA), enoxacin (ENX), ofloxacin (OFLX), ciprofloxacin (CPFX), lomefloxacin (LMFX) and DR-3355 (s-isomer of OFLX), and immediately exposed to ultraviolet-A (UVA) for 4 h (21.6 joules/cm2). The ears were examined for overt damage, as a major phototoxic parameter, 0, 24 and 48 h after irradiation ended. At doses of 200 mg/kg, LMFX, NA and ENX caused marked cutaneous phototoxic reactions on the ears, whereas CPFX, OFLX and DR-3355 caused none. At 800 mg/kg, however, CPFX, OFLX and DR-3355 also caused phototoxic reactions on the ears. These phototoxic changes were characterized grossly by erythema, and histopathologically by edema and infiltration of inflammatory cells, especially neutrophils, into the connective tissue surrounding the cartilage. The 50% erythema-inducing doses of LMFX, ENX, NA, OFLX, DR-3355 and CPFX were calculated at 19, 102, 143, 553, 619 and 741 mg/kg, respectively. Thus, the phototoxic potencies of the quinolones tested were: LMFX greater than ENX, NA greater than OFLX, DR-3355, CPFX. PMID- 2260127 TI - Prochloraz as potent inhibitor of benzo[a]pyrene metabolism and mutagenic activity in rat liver fractions. AB - We have determined how prochloraz, an imidazole antifungal agent, affects the metabolism of benzo[a]-pyrene by hepatic microsomes from 3-methylcholanthrene treated male rats. The prochloraz-like 7,8-benzoflavone was a potent inhibitor of total benzo[a]pyrene metabolism while miconazole was a weak inhibitor. The proportion of benzo[a]pyrene dihydrodiols formed was decreased whereas phenols were increased by the in vitro addition of prochloraz. Furthermore, a good correlation was obtained between the effects of prochloraz on the microsomal formation of benzo[a]pyrene metabolites and on the mutagenic activity of benzo[a]pyrene in the Salmonella typhimurium test. PMID- 2260128 TI - Lack of detectable metabolism for solubilized 2,3,4-trimethylpentane by rat kidney proximal tubules. AB - Primary proximal tubule suspension cultures exposed to solubilized 2,3,4 trimethylpentane (2,3,4-TMP) resulted in a linear dose response, as determined by cellular lactate dehydrogenase leakage. The EC50 for 2,3,4-TMP was 16.3 mM. Metabolite analysis by gas chromatography/mass spectrometry of supernate and cell extracts from cultures exposed to 2,3,4-TMP (12.0 mM) failed to detect the presence of metabolites. Electron-microscopic examination of proximal tubules exposed to 2,3,4-TMP indicated ultrastructural changes that included increased mitochondrial swelling, increased vesiculation, decreased microvilli and pyknotic nuclei. This study indicates that kidney proximal tubules do not appear to metabolize 2,3,4-TMP. PMID- 2260129 TI - The effect of arsenic trioxide on brain monoamine metabolism and locomotor activity of mice. AB - The arsenic trioxide (AsT) content, and monoamine levels in the cerebral cortex, hippocampus, hypothalamus and corpus striatum were determined in mice administered AsT (3 and 10 mg/kg) for 14 days. The vertical and horizontal motor activity was also examined. The AsT content in discrete brain areas differed but was clearly dose-dependent. Metabolites of norepinephrine and dopamine increased in the cerebral cortex, hippocampus and hypothalamus and decreased in the corpus striatum in AsT-treated mice. Metabolites of 5-hydroxytryptamine increased in all the discrete brain areas. The vertical and horizontal motor activity was increased by AsT at 3 mg/kg and decreased by AsT at 10 mg/kg. These results show that AsT modifies CNS metabolism and function at low doses. AsT penetrates the blood-brain barrier to cause these effects. PMID- 2260130 TI - Nimodipine prevents postischemic brain damage in the early phase of focal cerebral ischemia. PMID- 2260131 TI - Neuroprotective effect of nimodipine is not mediated by increased cerebral blood flow after transient forebrain ischemia in rats. AB - In the present study, we investigated the protective effect of nimodipine against postischemic neuronal damage in the rat and considered the question of whether this histologic finding coincides with an improvement of cerebral circulation. Male Wistar rats were subjected to 10 minutes of forebrain ischemia by clamping both common carotid arteries and lowering blood pressure to 40 mm Hg. Histologic evaluation was performed 7 days after ischemia. Local cerebral blood flow was determined with the 14C-iodoantipyrine technique in anatomically defined areas of the brain, including hippocampus. Preischemic application of nimodipine (3.0 mg/kg p.o.) significantly reduced the percentage of damaged neurons in hippocampal CA1 subfield from 78 +/- 4% in controls to 59 +/- 6% in treated rats (mean +/- SEM; p less than 0.05, Mann-Whitney U test). After 10, 60, and 180 minutes of recirculation no differences in local cerebral blood flow between control and drug-treated animals were observed. Our results demonstrate that nimodipine reduces ischemia-induced neuronal damage in rat hippocampus. We did not consider increased cerebral blood flow in the hypoperfusion state in the applied experimental design since improvement of cerebral blood flow seems to bear little relation to the neuroprotective activity of nimodipine. PMID- 2260132 TI - Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine. AB - We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect. PMID- 2260133 TI - Effects of early onset of nimodipine treatment on microvascular integrity in the aging rat brain. AB - We studied the effects of long-term treatment with 1,4-dihydropyridine nimodipine on age-related changes of the cerebral microvasculature in layers I, III, and V of the frontoparietal motor cortex of aged (30 months) male Wistar rats. Ultrastructural alterations of microvessels can either be attributed to degeneration or to deposition processes. Nimodipine application, irrespective of the time of onset, did not interfere with the degeneration of microvascular pericytes. However, nimodipine treatment from 24-30 months significantly reduced the amount of microvascular deposition products in cortical layers I and III, while an earlier onset (16 months) of the drug application resulted in a significant reduction in all motor cortex layers studied. This indicates a different susceptibility of microvessels in layer V of the frontoparietal motor cortex. These results show a beneficial effect of nimodipine on the integrity of cerebral microvasculature during aging and may provide a morphologic basis for the improved motor and cognitive performance in aged rats after chronic nimodipine application. PMID- 2260134 TI - Intracellular brain pH and ischemic vasoconstriction in the white New Zealand rabbit. PMID- 2260135 TI - Nimodipine prevents delayed neuronal death of sector CA1 pyramidal cells in short term forebrain ischemia in Mongolian gerbils. AB - Delayed death of pyramidal neurons of Ammon's horn CA1 sector after short-term forebrain ischemia in Mongolian gerbils represents a type of ischemic neuronal injury in which calcium influx plays an important role. We evaluated the influence of the calcium channel blocker nimodipine in animals subjected to 7.5 minutes of bilateral carotid artery ligation that were given 1 mg/kg i.p. nimodipine at various periods in relation to the ischemic incident. The control animals were subjected to cerebral ischemia with no medication. Five days after ischemia, the state of CA1 sector neurons was morphometrically evaluated and compared with that in animals not subjected to an experimental procedure. Nimodipine exerted a full protective effect on CA1 pyramidal neurons only after repeated application extending over 24 hours after the ischemia. A less conspicuous effect was obtained with a single dose applied at a late postischemic period, and a double dose given in the peri-ischemic stage remained ineffective. The time-dependent effectiveness of nimodipine is discussed in relation to the characteristics of this model of cerebral ischemia. PMID- 2260136 TI - Efficacy of nimodipine in cerebral ischemia or hemorrhage. AB - Our studies showed that in an appropriate dose, nimodipine increased local cerebral blood flow with no corresponding increase in local metabolism. Nimodipine treatment given before experimental ischemic insult, resulting from either vascular occlusion or intracranial hemorrhage or after subarachnoid hemorrhage, maintained or improved blood flow and minimized the severity of subsequent brain damage. Lack of benefit from nimodipine treatment after the insult may occur because the inexorable progression of events leading to ischemic neuronal damage, once initiated, cannot be arrested. On the other hand, pharmacokinetic factors may be important, and post-treatment efficacy may depend on administration protocols that achieve an adequate concentration in ischemic tissue sufficiently soon after an insult. Our findings are compatible with the benefit of nimodipine being due to an improvement in blood flow that reduces the severity of ischemia. However, they do not exclude the possibility that treatment may minimize the accumulation of calcium in damaged cells as a result of "cytoprotective" effects. PMID- 2260137 TI - Thromboxane biosynthesis in cardiovascular diseases. AB - Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin suppressable periprocedural thrombotic complications. On the other hand, both non insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2 dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities. PMID- 2260138 TI - Thromboxane synthase. From isolation to function. PMID- 2260139 TI - Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits. AB - Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2 induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases. PMID- 2260140 TI - Effects of the novel thromboxane antagonist Bay U 3405 on experimental coronary artery disease. AB - Bay U 3405 is a novel thromboxane receptor blocker. The present investigations describe its effects on experimental canine and porcine cardiac damage. In anesthetized dogs, a coronary artery was occluded for 6 hours and reperfused for 30 minutes. Bay U 3405 was administered intravenously 15 minutes after occlusion (1 mg/kg) followed by infusion of 10 mg/kg/hr from 30 minutes after ligature. In a second study, the effects of Bay U 3405 on endoperoxide analogue U-46619 induced coronary constriction were studied in anesthetized, open-chest pigs. Bay U 3405 reduced myocardial infarct expansion by 65% (p less than 0.01) assessed with biochemical staining. Hemodynamics and collateral blood flow were unaffected. However, reperfusion arrhythmias were suppressed. In porcine experiments, 1 mg/kg Bay U 3405, given intravenously or intraduodenally, antagonized U-46619-induced coronary vasoconstriction over 5 hours. The studies demonstrate anti-ischemic and antivasoconstrictor properties of Bay U 3405 probably due to binding to platelet and smooth muscle thromboxane receptors. This may have clinical relevance in angina pectoris and myocardial infarction. PMID- 2260141 TI - Bay U 3405 inhibits cerebral vasospasm induced by authentic thromboxane A2. AB - Platelet activation results in the formation of various vasoactive mediators such as thromboxane A2 and serotonin. We investigated the effects of Bay U 3405 [(3R) 3- (4-fluorophenyl-sulfonamido)-1,2,3,4,-tetrahydro-9-carbazolepro panoic acid] on vasocontractions of isolated bovine cerebral arteries induced by U 46.619, a stable thromboxane/prostaglandin-endoperoxide analogue, and authentic thromboxane A2 released from thrombin-stimulated human platelets. Bay U 3405 (0.001-10 mumol/l) potently inhibited the contraction induced by U 46.619 and demonstrated a reduction of the thromboxane-mediated component of platelet-induced contractile response at higher concentrations (0.1-10 mumol). PMID- 2260142 TI - Relevance of focal cerebral ischemia models. Experience with fibrinolytic agents. AB - Despite the limitations of individual ischemia models, experience with fibrinolytic agents suggests that 1) early intervention with rt-PA may result in rapid thrombolysis, functional recovery, and decreased mortality in small animal stroke thromboembolism models, 2) rt-PA has no general effect on clinical recovery following MCA occlusion and reperfusion in the nonhuman primate at dose rates capable of producing very high circulating rt-PA levels, while u-PA has an apparently salutary effect, and 3) intravenous infusion of rt-PA or u-PA early after ischemia/infarction in several model systems is not associated with significant intracerebral hemorrhage. The true clinical relevance of these general impressions must await the completion of human studies and studies in well-conceived models designed to define the vascular consequences to be expected from reperfusion achievable with thrombolytic agents. PMID- 2260143 TI - Effects of ipsapirone on spatial and temporal changes in somatosensory evoked potentials after middle cerebral artery occlusion in the rat. AB - The present study investigates the effects of the 5-hydroxytryptamine1A agonist ipsapirone on electroencephalography and somatosensory evoked potentials after middle cerebral artery occlusion in the rat. We implanted 17 silver ball electrodes symmetrically distributed over the skull in 14 rats and registered electroencephalography activity and somatosensory evoked potentials before, 1 hour, and 1 week after permanent occlusion of the left middle cerebral artery. Before vessel occlusion, a symmetric distribution of electroencephalography power was seen over both hemispheres. Middle cerebral artery occlusion caused a complete abolishment of electroencephalography power in the frontolateral aspects of the affected hemisphere. When electroencephalographic recordings 7 days after the insult were superimposed with three-dimensional-reconstructed pictures of the infarct, a close correspondence of the extention and spatial orientation was noted. Two negative and two positive peaks were consistently recorded before middle cerebral artery occlusion. In both control and ipsapirone-treated (30 mg/kg i.p. 30 minutes after induction of ischemia) animals, the vessel occlusion caused a severe reduction in amplitudes of somatosensory evoked potentials in all areas under record (p less than 0.05). One week after middle cerebral artery occlusion, amplitudes of somatosensory potentials over the lesioned hemisphere were still significantly (p less than 0.05) lower than preischemic values in the control group. When compared with the corresponding values 1 hour after middle cerebral artery occlusion, an albeit insignificant tendency toward increased amplitudes was observed in most areas under record. By contrast, in ipsapirone treated animals, significant differences compared with preischemic values were no longer present 1 week after the vessel occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260144 TI - Protective effects of fructose-1,6-bisphosphate on survival and brain putrescine levels during ischemia and recirculation in the Mongolian gerbil. PMID- 2260145 TI - Aspirin and platelets in relation to cerebrovascular disease. PMID- 2260146 TI - Preventing stroke by the modification of risk factors. AB - Epidemiologic research has revealed the major risk factors in cerebrovascular disease. This review will concentrate on three important risk factors: elevated blood pressure, the most common and important, since it is responsible for up to 70% of all strokes; raised cholesterol; and smoking. These factors are important not only because they increase the risk of stroke, but also because they are amenable to modification by drugs, diet, or other interventions. Strategies to avoid stroke can either 1) try to produce substantial reductions, usually with drugs, in the level of the risk factor in the few individuals in the population with high levels (the "high-risk" approach), or 2) try to produce modest reductions in the level of the risk factor in every individual in the population, usually not with drugs but with lifestyle modification (the "mass" approach). The prevention of stroke could best be achieved through continuing medical efforts to deal with high-risk individuals and through political strategies to encourage a healthier lifestyle in the population as a whole. PMID- 2260147 TI - Aspirin in stroke prevention. An overview. PMID- 2260148 TI - Aspirin reduces the growth of medial and neointimal thickenings in balloon injured rat carotid arteries. AB - We analyzed the effect of Aspirin on the growth of experimentally induced vascular thickenings in rat carotid arteries. Vascular thickenings were induced by denudation of the endothelium in the left carotid artery with a balloon catheter. Administration of Aspirin-rich food (17.4 g/kg body wt/day) was started 1 week before and continued 2 weeks after injury. Nine rats were used. A control group of equal size received normal food. Sizes of the tunica media, the neointima, and the open vessel lumen were measured on cross sections of carotid segments with the aid of a videomorphometry system. The results show that in the Aspirin group, neointimal lesions are significantly smaller than in the control group (0.14 mm2 versus 0.23 mm2; p less than 0.5). Thickenings of the tunica media are also reduced (0.11 mm2 versus 0.12 mm2; p less than 0.5). It is suggested that Aspirin reduces both medial hypertrophy and neointimal outgrowth in injury-induced atherosclerosis. PMID- 2260149 TI - Historical aspects of pharmacologic research at Bayer. 1890-1990. PMID- 2260150 TI - Calcium antagonists and vasoconstrictor effects in intracerebral microarterioles. AB - The purpose of this work was to study the contractile activity of intracerebral microarterioles and their sensitivity to the calcium antagonist nimodipine. Potassium depolarization evoked contraction and rhythmic activity that was blocked by nimodipine (IC50 0.08 nM). High concentrations of noradrenaline and prostaglandin F2 alpha were needed to elicit a contractile response. Intracerebral microarterioles were very sensitive to endothelin (ED50, 0.2 nM). The contractions evoked by concentrations of endothelin lower than or equal to ED50 were relaxed by nimodipine, which also blocked the amplified response to potassium chloride depolarization occurring with subthreshold concentrations of endothelin. We discuss these observations in relation to brain ischemia. PMID- 2260151 TI - Prevention of cerebrovascular spasms with nimodipine. PMID- 2260152 TI - Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage. AB - The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia. Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium. PMID- 2260153 TI - Effect of nimodipine on acute ischemic stroke. Pooled results from five randomized trials. AB - In a review of pooled data from five double-blind, placebo-controlled studies of nimodipine in acute ischemic stroke, we compared the effect of 120 mg nimodipine given orally with that of placebo. In the five studies, 871 patients were followed, and 781 adhered to entry and inclusion criteria. End points were mortality and outcome at the end of the treatment period (21 or 28 days). Outcome was assessed with Mathew's scale and the physician's clinical judgement. The treatment and control groups were well matched with respect to demographic data, risk factors, and baseline Mathew scores. In the treatment group, 34 patients (7.9%) died during the treatment period, whereas 54 (12.3%) in the control group died, corresponding with a mortality reduction of 36%. Significantly less neurologic impairment at the end of the treatment period was documented under nimodipine treatment, and this impairment improved more in patients with moderate to-severe stroke (baseline Mathew score less than 66) if administration of nimodipine occurred within 12 hours after stroke onset or if the patient was more than 65 years old. The overall incidence of adverse reactions was relatively modest, and these were of minor severity; only a few appeared to have more than a remote relation to the study medication. PMID- 2260154 TI - Pathophysiology of ischemic brain disease. AB - In this article, we review and discuss the pathophysiology of brain ischemia, focusing on requirements of cerebral metabolism, biochemical characterization of the energy reserve, and autoradiographic and tomographic methods for in vivo evaluation of cerebral blood flow and metabolism. We propose new therapeutic strategies for the management of the acute phase of stroke, based on diagnostic protocols that include clinical evaluation, noninvasive study of neck and intracranial arteries, brain computed tomography, and single-photon emission computed tomography. The ideal therapeutic trial should combine early thrombolysis and active brain protection against those biochemical mechanisms leading to irreversible neuronal damage. PMID- 2260155 TI - Effects of nimodipine on infarct size and cerebral acidosis after middle cerebral artery occlusion in the rat. AB - The objective of this study was to determine the effect of nimodipine on infarct development and local brain pH after middle cerebral artery occlusion in the rat. Female Fischer-344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation. After 6, 12, or 24 hours, brains were frozen, and infarct size, degree of edema formation, and local brain pH were quantified by standard histology or the umbelliferone technique, respectively. In control rats, cortical infarct size was increased from 29.5 microliters at 6 hours to 72.5 microliters at 24 hours after vessel occlusion. In striatum only, an insignificant increase from 15.2 to 24.7 microliters in infarct volume was observed during this period. Edema increased from 7% to 22% in cortical and from 4% to 39% in the striatal infarct areas during this time. Nimodipine (0.1 mg/kg s.c.), given 45 minutes before and again 8 and 16 hours after middle cerebral artery occlusion, did not alter infarct size at 6 hours but considerably improved outcome at later times. Edema formation was lower at 12 hours in the group treated with the calcium antagonist (p less than 0.05). By contrast, effects on local brain pH were seen as early as 6 hours after the vessel occlusion. Nimodipine greatly reduced the areas exhibiting the lowest pH values beyond pH 6.0 (p less than 0.05). Similar effects by nimodipine on brain pH were observed in the 12-hour series, whereas at 24 hours after middle cerebral artery occlusion, a shift to more alkalotic values was noted with no overt differences between control and drug-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260156 TI - Reversal of neurotoxin-induced ornithine decarboxylase activity in rat cerebral cortex by nimodipine. A potential neuroprotective mechanism. AB - An increase in the activity of the enzyme ornithine decarboxylase has been shown to be associated with ischemia and other lesions of the nervous system. We have previously characterized the induction of ornithine decarboxylase in cerebral cortex following excitotoxin lesion of the nucleus basalis and have shown it to be sensitive to treatment with MK-801 up to 4 hours after the lesion and to be associated with an early increase in ornithine decarboxylase mRNA. In this study, we have used this model to investigate the effect of dihydropyridines on this response to lesion. Injection of 1 micrograms kainate into the nucleus basalis causes a large increase in ornithine decarboxylase activity that is maximal at 8 hours (292 pmol/mg/hr) when there is a 200-fold increase in ornithine decarboxylase activity compared with unoperated control animals (1.4 pmol/mg/hr). Treatment of animals with nimodipine either 5 minutes before or 60 minutes after lesion did not affect the maximal ornithine decarboxylase response at 8 hours. However, repeated injections (four of nimodipine, 10 mg/kg) significantly (p less than 0.001) attenuated the response to lesion by 75%. Injections were given 5 minutes before lesion and at 1.0, 3.5, and 6.0 hours after lesion. The efficacy of this treatment regimen indicated that maintaining a blockade of dihydropyridine-sensitive channels over this period was necessary to attenuate this induction of ornithine decarboxylase. To investigate the critical period over which dihydropyridines might be effective, their action at the earlier time point of 4 hours was tested where a significant induction of ornithine decarboxylase occurs (60 pmol/mg/hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260157 TI - Effect of nimodipine on glucose metabolism in the course of ischemic stroke. AB - We investigated the effect of the calcium channel-blocking agent nimodipine on regional cerebral metabolic rate of glucose in acute ischemic middle cerebral artery infarction diagnosed clinically and by computed tomography. Twenty-seven patients entered the study within 48 hours after onset of symptoms and randomly received either nimodipine (2 mg/hr constant intravenous infusion for 5 days, 120 mg/day orally for another 16 days) or placebo. Four of the 27 patients died within the first 3 weeks and could not be evaluated. Of the remaining 23 patients, 11 were assigned to the nimodipine group and 12 to a control group. We analyzed data from positron emission tomography, performed twice before and after completion of therapy, and clinical data from the treatment period and the next 6 months based on the Mathew Score for early assessment and the Barthel Index for late assessment. During the post-treatment period, two patients from the nimodipine group and three from the control group died. The evaluated patients were comparable for age and sex distribution, initial clinical deficit, and infarct size and localization. We found significant metabolic changes between both treatment groups for contralateral infarct mirror region, ipsilateral and contralateral cerebral gray matter, and contralateral and ipsilateral cerebellar hemispheres (side x region x treatment interaction p less than 0.025). The nimodipine group had bilaterally increased regional cerebral metabolic rate of glucose of morphologically intact cerebral (14.6% and 17.1%, respectively) and cerebellar structures (6.9% and 10%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260158 TI - Drug-resistant malaria: mechanisms of development and inferences for malaria control. PMID- 2260159 TI - The pituitary-thyroid axis in severe falciparum malaria: evidence for depressed thyrotroph and thyroid gland function. AB - Abnormal thyroid function is strongly associated with mortality in severe non thyroidal illness. We have assessed the pituitary-thyroid axis serially in 18 Thai adults with severe falciparum malaria and in 18 matched controls. The admission total serum thyroxine (T4) concentrations of the patients (median [range]: 64 nmol/litre [less than 30-91]) were significantly lower than those of controls (81 nmol/litre [61-133]; 2P less than 0.01), and remained depressed until after fever and parasite clearance. Two patients who died in hospital had admission serum T4 concentrations less than 35 nmol/litre. The admission basal serum thyrotropin (TSH) levels of the patients (0.9 mU/litre [less than 0.2-3.1]) were similar to those of controls (1.3 mU/litre [less than 0.2-3.7], 2P greater than 0.1) and remained normal throughout fever and parasitaemia. Thirty-minute TSH increments during a thyrotropin-releasing hormone test on admission were reduced in 13 patients with severe malaria (4.1 mU/litre [0.7-8.1]) relative to those in convalescence (7.1 mU/litre [1.7-14.4], n = 10, 2P less than 0.01) and controls (5.6 mU/litre [3.3-12.9], n = 9, 2P less than 0.05). These findings suggest that thyrotroph and thyroid gland function are depressed during acute, severe malaria. As these changes may be an adaptation to accelerated catabolism, the role of thyroid replacement in such patients is uncertain. PMID- 2260160 TI - The clinical and parasitological presentation of Plasmodium falciparum malaria in Uganda is unaffected by HIV-1 infection. AB - The relation between Plasmodium falciparum malaria and symptomatic human immunodeficiency virus 1 (HIV-1) infection was investigated in paediatric and adult patients in Kampala, Uganda, from 1987 to 1989. Both infections contributed largely to hospital morbidity. Of 1527 clinically suspicious in-patients, 61% were positive for HIV-1 infection. 52% of patients with positive HIV-1 serology fulfilled the World Health Organization clinical case definition for acquired immune deficiency syndrome (AIDS) in Africa. No association could be found between HIV-1 infection and malaria either in paediatrics or in adults. P. falciparum parasitaemia was present in 18% of all patients and no differences in prevalence of malaria infection or in parasite density could be demonstrated between HIV-1 positive and HIV-1 negative patients. The comparison of clinical symptoms showed typical differences in AIDS-related morbidity but no difference in malaria-specific morbidity. Also, the response to malaria treatment was the same in HIV-1 positive and HIV-1 negative patients. P. falciparum malaria does not appear to act as an opportunistic agent in AIDS patients in Uganda. PMID- 2260161 TI - A longitudinal study of antibodies to the Plasmodium falciparum antigen Pf155/RESA and immunity to malaria infection in adult Liberians. AB - 118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults. PMID- 2260162 TI - Plasmodium falciparum infection does not increase the precocious mortality rate of Anopheles gambiae. PMID- 2260163 TI - The malaria eradication programme in Algeria: present situation. PMID- 2260164 TI - Failure of anti-malarial prophylaxis with mefloquine in Africa. PMID- 2260165 TI - Hypoglycaemia in pregnant women with malaria. PMID- 2260166 TI - Mononeuritis multiplex in Plasmodium falciparum malaria. PMID- 2260167 TI - Painless venepuncture in the field. PMID- 2260168 TI - Released glycoconjugate of indigenous Leishmania major enhances survival of a foreign L. major in Phlebotomus papatasi. AB - The effect of Leishmania glycoconjugate in the vector was investigated using Phlebotomus papatasi artificially infected with a Leishmania major strain that this vector does not transmit in nature. Glycoconjugate of the vector-specific strain of L. major was added to the infective meals of some fly groups and the success of infections with or without this substance was compared 4 d later. In the absence of glycoconjugate the parasites survived in 15.6% of the flies, while the addition of 0.5 mg/ml and 2 mg/ml raised the rate of infection to 34.3% and 63.0% respectively. Undigested blood was found in the stomach of 7.8% of the infected flies, whereas following meals with parasites and 2 mg/ml glycoconjugate it was present in 37% of the flies. The results demonstrated that this glycoconjugate increased the viability of the parasites in the unsuitable vector and delayed digestion of the infective meals. In a parallel experiment the glycoconjugate of L. donovani did not affect the survival of the parasites. PMID- 2260169 TI - Severe arthralgia, not related to dose, associated with pentavalent antimonial therapy for mucosal leishmaniasis. PMID- 2260170 TI - Enzyme-linked immunosorbent assay in the diagnosis of kala-azar in Bhadohi (Varanasi), India. AB - An enzyme-linked immunosorbent assay (ELISA) developed using Leishmania donovani promastigote soluble antigen gave positive responses in practically all the clinically and parasitologically diagnosed patients with kala-azar in a preliminary study. Healthy control subjects from non-endemic and endemic areas gave negative results. No cross-reaction was observed with patients having leprosy, filariasis, malaria, tuberculosis, or amoebiasis. Blood samples collected on filter paper were adequate for the test. The test appears promising in the diagnosis of kala-azar. PMID- 2260171 TI - Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime. AB - Seventy-nine patients with cutaneous (62) or mucosal (17) infection with Leishmania (Viannia) braziliensis in Tres Bracos, Bahia, Brazil, were followed for at least 4 years after initiating treatment with antimony. Cutaneous relapses occurred in 6/62 (10%), mucosal relapse after cutaneous infection in 2/62 (3%), and mucosal relapse after mucosal disease in 2/17 (17%). It is concluded that relapse (cutaneous and mucosal) is rare after adequate antimony therapy and that no definite prediction of relapse (clinical, serological or by skin reaction) is possible. PMID- 2260172 TI - Leishmaniasis in Sardinia. 5. Leishmanin reaction in the human population of a focus of low endemicity of canine leishmaniasis. AB - About half (640 subjects) of the population of Soleminis, a canine leishmaniasis focus 15 km north of Cagliari, Sardinia, was subjected to the leishmanin skin test. The total positive rate was 9.7%, and that of males was 15.5%. The age trend in the positive rate resembled a hyperbolic curve, with the 0-5 years age group rate being zero and the highest rate (39.3%) occurring in the 55-65 years age group. The Soleminis focus was classified as hypoendemic, with a prevalence of canine leishmaniasis of about 3%. Dog surveillance, land reclamation and changes in population habits during the last few decades are considered to be responsible for the reduction of transmission to man. PMID- 2260173 TI - Intestinal amoebiasis and giardiasis in southern Indian infants and children. AB - The role of Entamoeba histolytica and Giardia lamblia as causative agents of paediatric diarrhoea was studied in a southern Indian population. Relationship between infant feeding practices, co-existing malnutrition and the occurrence of intestinal amoebiasis and giardiasis was also examined. The subjects were 361 paediatric patients with acute diarrhoea and 70 hospitalized control children without diarrhoea. Faecal samples from cases and controls were examined for the protozoal pathogens using faecal preservatives, permanent staining and formalin ether concentration. Bacteriological studies were conducted on 244 of the 361 cases. A high prevalence of invasive amoebiasis was seen in the 0-6 month (12.5%) and 7-12 month (20.3%) age groups. Giardiasis was uncommon under 6 months (2.1%) but occurred in 8-10% of all other age groups. Invasive amoebiasis occurred mainly in children on weaning foods (45.9%) but also [corrected] in exclusively breast-fed children (13.5%). Giardiasis was not seen in exclusively breast-fed infants, but commonly occurred in older children on normal diets. There was no association between amoebiasis or giardiasis and malnutrition. PMID- 2260174 TI - Zymodemes of Entamoeba histolytica isolated in the Amazon and the north-east of Brazil. PMID- 2260175 TI - Immunoblot analysis of antibodies in human strongyloidiasis. AB - An electrophoretic transfer technique was used to investigate qualitatively the production of antibodies to Strongyloides stercoralis larvae in 56 patients with strongyloidiasis. SDS-PAGE analysis of the larval extract revealed the presence of at least 33-39 polypeptide bands under either reducing or non-reducing condition. In the immunoblot analysis, almost all patients showed positive reactivity to the polypeptide bands. The reactivity, however, revealed significant variation among the patients, ranging in number of bands from only one to more than 18. Among the bands, 4 with molecular sizes of 97, 66, 41 and 26 kDa were frequently recognized by the patients' sera, indicating that these antigenic components may form an available antigen for immunological testing for strongyloidiasis. On the other hand, the reactivities were very faint in cases of overwhelming strongyloidiasis. PMID- 2260176 TI - Differential humoral and cellular immunoreactivity to saline- and detergent extracted filarial antigens. AB - The immunoreactivity to saline- and detergent-extracted filarial antigens of 31 Haitian subjects exposed to or infected with Wuchereria bancrofti was analysed. Cellular reactivity, monitored by blastogenesis in vitro, was significantly greater to a soluble extract of Brugia pahangi than to a detergent-extracted antigenic preparation. In contrast, serum antibody levels against the detergent extract were significantly higher. These differences were consistently observed in symptomatic, microfilaraemic, and asymptomatic/amicrofilaraemic groups of patients. These patterns of immunoreactivity may reflect intrinsic differences between the 2 antigenic preparations in terms of composition or their mode of presentation to the host immune system. PMID- 2260177 TI - The effects of ivermectin used in combination with other known antiparasitic drugs on adult Onchocerca gutturosa and O. volvulus in vitro. AB - The effects of ivermectin at a concentration of 3.13 x 10(-6) M used in combination with other antiparasitic drugs on the viability of adult Onchocerca in vitro were assessed using MTT colorimetry and worm motility levels. When ivermectin was used against male O. gutturosa over a 7 d period in combination with suramin (5 x 10(-5) M), CGP 6140 (3.13 x 10(-6) M), CGP 20376 (1.95 x 10(-7) M), mefloquine (3.13 x 10(-6) M), levamisole (3.13 x 10(-6) M), mebendazole (5 x 10(-5) M), flubendazole (5 x 10(-5) M) and albendazole (5 x 10(-5) M), there was either no increased effect or only a marginally increased effect on motility levels when compared with the use of ivermectin alone. MTT colorimetry revealed that in most cases there was a cumulative effect of the 2 drugs used in combination but not a synergistic effect. In a trial extended to 26 d it was demonstrated that the combination of ivermectin and suramin did not produce a greater inhibition of motility than ivermectin alone. Using female O. volvulus, the activity of ivermectin, CGP 6140 and the 2 drugs combined was examined. The motility of all 3 groups exposed to drug(s) was suppressed by 24 h compared with controls. MTT colorimetry performed on day 7, using the pre-weighed anterior end of each worm, illustrated that ivermectin alone produced a 43.4% inhibition of formazan formation compared with controls, CGP 6140 alone produced 50.6% inhibition, while the drug combination produced a 72% inhibition, equivalent to the heat-killed control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260178 TI - Examination of faecal specimens by the formalin-detergent technique. PMID- 2260179 TI - Survival of toxigenic Vibrio cholerae O1 with a common duckweed, Lemna minor, in artificial aquatic ecosystems. AB - Cholera epidemics occur twice a year in Bangladesh. During epidemics, Vibrio cholerae O1 are isolated from patients, as well as from the surface water, but the bacteria disappear during inter-epidemic periods. Their reservoirs or sites of survival and multiplication during inter-epidemic period are still unknown. The present survival study in the laboratory explored the role of an aquatic plant, Lemna minor (duckweed), as a possible reservoir. L. minor was added to sea salt solution at pH 8.5, containing V. cholerae. Survival of V. cholerae on L. minor, in water on which L. minor was floating, and in control water (without L. minor) was monitored at regular intervals. Survival of both environmental and clinical strains of V. cholerae was assessed by viable counts on thiosulphate citrate-bile salt-sucrose agar. It was observed that both strains survived better on L. minor than in water on which L. minor was floating or in control water. It is suggested that plants may serve as an effective environmental reservoir for V. cholerae either through a non-specific association or by interaction with V. cholerae in commensal relationship. PMID- 2260180 TI - An avidin-biotin enzyme-linked immunosorbent assay for the detection of Pseudomonas pseudomallei antigens. PMID- 2260181 TI - BCG ulcers and their effect on mothers' willingness to allow their children to receive other antigens. PMID- 2260182 TI - Reduction in diarrhoeal diseases in children in rural Bangladesh by environmental and behavioural modifications. AB - The impact of a water, sanitation and hygiene education intervention project on diarrhoeal morbidity in children under 5 years old was evaluated in a rural area of Bangladesh. Data were collected throughout 1984-1987, covering both pre- and post-intervention periods, from an intervention and a control area. The 2 areas were similar with respect to most socio-economic characteristics and baseline levels of diarrhoeal morbidity. The project showed a striking impact on the incidence of all cases of diarrhoea, including dysentery and persistent diarrhoea. By the end of the study period, children in the intervention area were experiencing 25% fewer episodes of diarrhoea than those in the control area. This impact was evident throughout the year, but particularly in the monsoon season, and in all age groups except those less than 6 months old. Within the intervention area, children from households living closer to handpumps or where better sanitation habits were practised experienced lower rates of diarrhoea. These results suggest that an integrated approach to environmental interventions can have a significant impact on diarrhoeal morbidity. PMID- 2260183 TI - Collembolan insects as potential parasites. PMID- 2260184 TI - The use of fermented and germinated cereals and tubers for improved feeding of infants and children in Uganda. AB - Interviews with mothers in 4 ecologically separate regions of Uganda (Arua, Mukono, Kabale and Mbarara) revealed considerable differences in patterns of infant and child feeding in health and during diarrhoea. There was considerable enthusiasm for the use of fermentation and germination of cereals and tubers in some areas (Arua 87% and Kabale 90%). These household food processes were especially recommended for improving dietary intake during diarrhoea. However, these techniques were not used by mothers in Mukono or Mbarara. The advantages of these procedures and possible reasons for differences in their popularity are discussed. PMID- 2260186 TI - Royal Society of Tropical Medicine and Hygiene laboratory meeting. 16 November 1989. Abstracts. PMID- 2260185 TI - Acute myocardial infarction-like enzyme profile in human victims of Crotalus durissus terrificus envenoming. AB - The clinical signs and symptoms of Crotalus durissus terrificus envenoming are due to the neurotoxic, myotoxic systemic and thrombin-like coagulating effects of the venom. The rhabdomyolysis observed after envenoming caused by snakes, the venom of which has a systemic myotoxic activity, has been limited thus far to skeletal muscle, with no reports of myocardial damage. In the present paper we report serial measurements of serum creatine kinase (CK), lactic dehydrogenase (LD) and of CK-MB and LD1 isoenzymes in human victims of Crotalus bites. The results were similar to those reported for acute myocardial infarction even though the clinical evolution, electrocardiogram and echocardiogram findings did not show any involvement of cardiac muscle. The enzymatic profile detected, as well as the pattern of focal involvement observed in muscle biopsies obtained from these patients, suggest that there may be a type of skeletal muscle fibre that is preferentially damaged by C. durissus terrificus venom, i.e., type I and/or IIa fibres, the composition of which is richer in CK-MB and LD1, and is similar to that of cardiac fibres. PMID- 2260187 TI - On the establishment in culture of isolates of Plasmodium falciparum. PMID- 2260188 TI - Human dicrocoeliasis. Report on 208 cases from Saudi Arabia. AB - In 3 years, Dicrocoelium dendriticum ova were detected in 208 patients at the Armed Forces Hospital, Riyadh, Saudi Arabia during 1984-1986. At least 7 of these patients had a true infection and at least 34 patients had spurious infection as they gave a history of eating raw liver. 23% of the 208 patients were under 14 years of age. The peak incidence was between October and November in each of the 3 years. 134 of these patients were symptomatic. 16 patients had disturbed liver functions and 13 had eosinophilia. 10 patients had gall bladder or biliary tree disease and in at least 2 of which it was due to D. dendriticum. Malabsorption occurred in one patient. Praziquantel was used in 9 patients and was successful in treating 4 of these patients. PMID- 2260189 TI - The sensitivity of dermatophytes to griseofulvin. AB - 13 isolates of Trichophyton violaceum and 7 Microsporum langeroni from Zambia and Cameroon were tested in vitro for their sensitivity to griseofulvin. No strain was found resistant. All the 13 T. violaceum were inhibited by 4-8 micrograms/ml while 4 M. langeroni were inhibited by 0.5-1 microgram/ml. PMID- 2260190 TI - Could potash facilitate the acceptation of cereal-based oral rehydration solution in the northern part of Nigeria? PMID- 2260191 TI - The bacteriology of appendicitis and its septic complications in Zaria, Nigeria. AB - Two hundred and seventy nine case notes of patients with confirmed appendicitis seen over a five year period at the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, were studied retrospectively and 100 patients were studied prospectively for the bacterial flora of appendicitis and its septic complications. Escherichia coli was the most frequently isolated aerobe while Bacteroides species were the most common anaerobes in both aspects of the study. Gentamicin, chloramphenicol and metronidazole are suggested as the most useful drugs in the management of complicated cases of appendicitis in this environment. PMID- 2260192 TI - Haematuria and sickle cell disease. A report of 12 cases and review of the literature. AB - Haematuria in a patient with S-haemoglobin poses a serious challenge of diagnosis and treatment. The first problem is to determine whether the haematuria is incidental or whether it is truly related to the S-haemoglobin. The second is to stop further blood loss. Twelve cases of haematuria induced by sickle cell disease, diagnosed through positive urographic findings of papillary necrosis and successfully treated without any loss of kidney are presented. The pathophysiology of sickle cell-induced haematuria, its incidence rate, its diagnostic criteria and available modalities of treatment are also reviewed in order to improve the diagnosis and treatment of this lesion in our subregion. It is suggested that the diagnosis of sickle cell induced haematuria should be based on identifiable features and not merely by exclusion of other lesions. PMID- 2260193 TI - Maternal and foetal outcome of pregnant patients with sickle cell anaemia at Kenyatta National Hospital Nairobi. A retrospective study. AB - In a retrospective study we assessed pregnancy outcome in relation to sickle haemoglobin (HbS) and anaemia at Kenyatta National Hospital, Nairobi (KNH) from 1981-1986. There were 36% maternal and 45% foetal losses in sickle cell disease (SCD) pregnants and 7% foetal losses in sickle cell trait (HbAS) from 26 HbS related pregnancies. 11 had homozygous sickle cell (SS) disease and 15 had HbAS. Age ranges for both groups were comparable. Mean haemoglobin-level for SS disease patients was 7.8 gm/dl (SD +/- 1.68), for AS patients 7.8 gm/dl (SD +/- 2.1). These maternal and foetal losses are quite high. Anaemia alone does not satisfactorily account for the higher losses in SS pregnancies. Other contributory factors need elucidation and intervention. PMID- 2260194 TI - Haemophilia in Zimbabwe. AB - Of the 120 haemophiliacs diagnosed in Zimbabwe in 8 years, haemophilia A and Christmas disease accounted for 90% and 10% respectively (i.e. a ratio of 9:1). Although the clinical and laboratory parameters were essentially similar to those previously described in Caucasian, African and other populations in the World, sub-haemophiliac cases are probably still being missed particularly in very busy health centres where the index of suspicion is low and malnutrition and infectious disease predominate and therefore readily attract the attention of most health workers. However, with the steadily improving socio-economic status and decentralization of health care facilities, more of these cases are likely to be diagnosed. Major constraints in the diagnosis and management of haemophilia in an African setting are succinctly discussed; including home therapy; and the implications of recent findings of HIV sero-positivity. The study serves as evidence that haemophilia is common in Zimbabwe contrary to earlier published literature. PMID- 2260195 TI - Intestinal ascariasis in the differential diagnosis of peptic ulcer disease. AB - 865 patients who had barium meal examination for clinical suspected peptic ulcer disease were studied. Out of these, 175 patients (20.2%) had no radiological evidence of peptic ulcer disease but were found to be infested with ascaris worms and their symptoms abated with the use of anthelminthics. None of the 93 patients who had haematemesis and gastric outlet obstruction had intestinal ascariasis. It is therefore suggested that in patients with symptoms of peptic ulcer disease, provided there are no complications, plain abdominal radiographs, stool examination and possibly therapy for helminths should be carried out before ordering barium meal examination. PMID- 2260196 TI - Henoch Schonlein purpura in Arab children. Analysis of 52 cases. AB - Over a period of 6 years (October 1981 through September 1987) 52 Arab children with Henoch Schonlein purpura were studied retrospectively. The annual incidence was estimated to be 6.7/100,000 children under the age of 12 years. The mean age at onset was 5.6 years, and in a mean follow-up period of three years, there was no mortality; three children developed intussusception and one child developed chronic renal failure and progressed to end stage kidney disease. The clinical profile of the disease was essentially similar to other reports. However, unusual features observed in this study included the development of the disease following herpes virus infection in two patients, the involvement of the temporo-mandibular joint in one and bullous lesions in another. The additional distribution of the typical rash over the flexor surface of the lower limbs in our patients was not reported before. PMID- 2260197 TI - Histological examination of blood vessels in peripheral gangrene among patients with sporadic outbreak of ergotism. AB - During the academic year 1985-1986 at Gondar College of Medical Sciences Hospital gangrenous ergotism was clinically diagnosed in seven patients (5 males, 2 females) ranging in age from 20 to 45 years. Amputation and subsequent histological examination of the blood vessels revealed occluded tibial arteries by acute thrombosis without cellular reaction or inflammatory lesion of the arterial wall in 3 patients. Endangitis with organized arterial thrombosis and focal recanalization of the vessels was noted in the remaining four patients. The smaller arterial branches including the dorsal pedal artery appeared to be contracted with knobby projections into the lumen. The latter was occluded by chronic, organized thrombosis in all patients. The present finding indicates that thrombosis and its organization could be another pathogenic factor in the development of gangrene due to ergotism, which is a histological picture similar to that of thrombangitis obliterans. PMID- 2260198 TI - Sorghum-based oral rehydration solution in the treatment of acute diarrhoea. AB - Sixty four children between 2.5 months and 5 years of age were randomly treated in a country hospital in Jos, Nigeria, with either the oral rehydration solution (ORS) as recommended by the World Health Organisation (WHO) or a cereal-based electrolyte solution, containing 60 g/l sorghum powder. Both groups were well comparable in many aspects, except for the nutritional status and the use of ORS before admission. In both aspects the sorghum-ORS group was at a disadvantage. During treatment there were no significant differences between the two groups in amount of fluid used, number of stools and duration of diarrhoea. Though weight gain in the two treatment groups was not significantly different, median weight gain in the sorghum-ORS group was 295 g, vs 155 in the WHO-ORS group. Seven children died, two (6%) in the sorghum-ORS group and five (17%) in the WHO-ORS group. Sorghum-ORS was well accepted and tolerated. This study suggests that sorghum-ORS can safely be used as an alternative in the treatment of diarrhoea. PMID- 2260199 TI - Possible transplacental transmission of Onchocerca volvulus. AB - In a recent epidemiological study on onchocerciasis on the lower Jos Plateau in Nigeria, a 7-month-old baby delivered by a mother suffering from onchocerciasis showed early clinical signs of the disease: pruritus was present all over the body. The infant's skin snip on incubation revealed microfilariae of Onchocerca volvulus. These findings were confirmed 3 months later when the child was re examined. No onchocercal nodule was found, but pruritus persisted. PMID- 2260200 TI - Cutaneous leishmaniasis in Sri Lanka. An imported disease linked to the Middle East and African employment boom. AB - Cutaneous leishmaniasis acquired by two Sri Lankan nationals while they were employed in Iraq and Northern Nigeria respectively constitutes examples of an imported disease related to the 'Middle East and African employment boom'. In both cases the diagnoses were confirmed by demonstrating the parasites in smears from the lesions and in tissue sections, and by culturing the parasites in vitro. Since leishmaniasis, neither visceral nor cutaneous is prevalent in Sri Lanka the risks of 'introduced' diseases is discussed here in the context of these two cases. PMID- 2260201 TI - Pharyngeal tuberculosis. AB - A case of pharyngeal tuberculosis is reported in a 54-year-old Chinese man. This is an uncommon condition and is often associated with pulmonary tuberculosis as in our patient. PMID- 2260202 TI - Mechanism of upper gastrointestinal hemorrhage in Mediterranean spotted fever. AB - Gastrointestinal (GI) hemorrhage is not a common complication of Mediterranean spotted fever (MSF). We describe three MSF cases with upper digestive tract bleeding in patients from Salamanca (Spain) and the results of the histologic studies performed in two of them. Besides the classical clinical triad of the disease (fever, rash and lesion at the site of tick bite, 'tache noire'), these patients presented purpuric rash and hypoalbuminemia, previously identified in severe forms of the disease. The hemorrhagic complication occurred late in the course of the MSF (between 13 and 20 days after the onset of fever) and was the consequence of multiple acute superficial erosions of the gastric mucosa. The histologic substrate of these lesions was identified as a vasculitic process - characteristically lymphohistiocytic - affecting the small vessels of the gastric wall. Rickettsial vascular injury at this level of the digestive tract is histologically similar to that observed in other organs in patients with MSF and may manifest clinically as digestive tract bleeding. PMID- 2260203 TI - Liposarcoma of the cervix. AB - The case of a 45-year-old woman with a fungating cervical mass which was diagnosed as liposarcoma is described. She had a recurrence which was excised six months later and there was no clinical evidence of metastasis. No report of a similar case has been found in the African literature and this is probably the first documented report. PMID- 2260204 TI - Transmission of Mycobacterium leprae from lepromatous leprosy patients to the skin of mice through intermittent feeding. AB - Batches of hungry Aedes aegypti mosquitoes which partially sucked blood from the skin lesions of proved untreated lepromatous leprosy (LL) patients were allowed immediately to feed on a portion of the skin of a cleanly shaved swiss mouse. The portion of the skin was cut, homogenized on the same day and extracted with chloroform. Out of 10 extracts, stained for acid fast bacilli (AFB), Mycobacterium leprae were demonstrated in eight, indicating transfer of bacilli mechanically to the biting spot through intermittent feeding. Out of 50 probosces dissected and stained for AFB, M. leprae were demonstrated in 45. PMID- 2260205 TI - Visceral leishmaniasis in Sudan. Clinical features. AB - Kala azar is a disease endemic to the Sudan and a cause of major morbidity and mortality to affected patients when the diagnosis or treatment has been delayed. In this report we described the clinical features of 99 parasite proven patients with visceral leishmaniasis. The Sudanese kala azar patient is young in age (teens to 20's), has marked weight loss despite a continuous, excellent appetite and suffers from insomnia, epistaxis and abdominal pain. Hepatosplenomegaly is universally present. Generalized lymphadenopathy is a prominent feature (72%). The high prevalence of lymphadenopathy has a wide range of implications: for diagnosis, i.e., the use of lymph node aspiration; for response to treatment, i.e., the resolution of lymphadenopathy; and for studies of immunoregulation in this systemic infection. PMID- 2260206 TI - Cryptosporidium gastroenteritis in immunocompetent children from Kuwait. AB - During an 18 months' survey of children admitted to hospital with gastroenteritis, oocysts of the protozoan Cryptosporidium were detected in 35 cases (1.6% of the total 2205 surveyed). The affected children (age range 5 months to 8 years; mean 34.2 months) were immunocompetent, and had green and offensive watery diarrhoea. Vomiting (94%) with dehydration (80%), fever (66%) and abdominal pain (26%) were major clinical features of the diarrhoeal illness which lasted a mean 8.2 (range 3-14) days. Five children were infected with other enteropathogens. The illness was self-limiting in all cases and none were excreting oocysts 2 weeks after cessation of diarrhoea. Peak incidence occurred during the months of March and April, with no cases during the hottest months of July and August. There was no known contact with animals or pets; 4 children had other siblings affected and 2 conformed to cases of travellers' diarrhoea. The significance of cryptosporidiosis in Kuwait and the need for epidemiological studies are discussed. PMID- 2260207 TI - Intestinal helminthiasis in ex-patriates returning to Britain from the tropics. A controlled study. AB - A retrospective study was performed of clinical features in expatriates attending the Hospital for Tropical Diseases, London, with a sole diagnosis of ascariasis (100), trichuriasis (100), hookworm (75), and strongyloidiasis (36). Results were compared with a control group of 100 ex-patriates attending the same hospital in whom no diagnosis was made and in whom stool microscopy and peripheral blood eosinophil counts were normal. Almost one half of all patients with intestinal helminthiasis were asymptomatic. Of those with symptoms specific clinical features were no different from controls with the exception of a transient itch or rash in patients with strongyloidiasis. The presence of eosinophilia was not a reliable indicator of infection. This study suggests that it may be worth while performing stool microscopy in ex-patriates returning from the tropics even if they are asymptomatic. PMID- 2260208 TI - Clostridium perfringens type C in bloody and watery diarrhea in Bangladesh. AB - A two-week age-matched case-control survey to detect Clostridium perfringens type C-associated illness was conducted among diarrheal patients hospitalized following the consumption of high protein meals on the occasion of an annual religious festival. From the stool of 33 patients screened, C. perfringens type C was isolated from one patient with bloody diarrhea and from two patients with watery diarrhea. In Bangladesh, C. perfringens type C has been isolated in both bloody and watery diarrhoeal illness and is not necessarily associated with necrotizing enteritis (pigbel). PMID- 2260209 TI - HIV seropositivity and tuberculosis in a large general hospital in Malawi. AB - The incidence of the acquired immunodeficiency syndrome (AIDS) in Malawi is one of the highest in Central Africa. Since tuberculosis is an important initial manifestations of the disease, consecutive patients admitted to the tuberculosis (TB) wards of Zomba General Hospital, Malawi, were asked for permission to undergo a human immunodeficiency virus (HIV)-antibodies test. In addition, two other studies were done: from September 1986 all medical in-patients, clinically suspected for immune deficiency and from April 1988 all blood donors were tested for HIV seropositivity. Seventy-five percent of the TB patients volunteered; 32 out of 125 (26%) were seropositive. In the high-risk age groups (20-40 years) this percentage rose to 32. Among the medical in-patients suspected of immune deficiency the seropositivity rose sharply from April 1987 to October 1988. Among the blood donors tested, 20% were seropositive. PMID- 2260210 TI - Is cryptococcal meningoencephalitis in the tropics a distinct entity? A retrospective study from Thailand. AB - Twenty-four consecutive patients with central nervous system cryptococcosis (C.C.) have been studied retrospectively. In contrary to many reports from America or Europe only two patients suffered from an underlying immunocompromising disease. All patients were treated uniformly by amphotericin B and 5-fluorocytosin. They were monitored closely and dose-adjustment was done according to laboratory data. None of the patients died. Sixteen were available for a six-month post-treatment follow-up: seven had various degrees of neurological long-term sequelae whereas nine had no complaints and neurological examination was without abnormal findings. Our series is compared with others both from tropical and non-tropical countries. In accordance with all but one larger series from the tropics the relatively good prognosis and extremely rare occurrence of C.C. in immunocompromised persons is noted. Since different varieties of Cryptococcus neoformans have been shown to exist in different climate zones, this might be one of the possible explanations for the lack of preceding immune-compromising conditions in persons suffering from C.C. in the tropics and the benign course of disease. PMID- 2260211 TI - Obesity and major metabolic indices in newly diagnosed Saudi diabetic patients. AB - Metabolic indices were assessed in 217 Saudi diabetic patients and 57 control subjects in relation to Body Mass Index (BMI). Patients with BMI values greater than or equal to 27 in male and greater than or equal to 25 in female were considered obese. Obesity was found more frequent in females (82.7%) than in males (40.9%) (p less than 0.01). Basal glucose and HbA1C levels were lower in obese males than in females. C-peptide levels were higher (p less than 0.01) in the obese subjects than in the non-obese. Within the obese group c-peptide levels were higher in males than in females. Triglycerides and total lipids were also higher in the obese group. Our result suggests that a varying degree of obesity influences the rate of both beta cell secretion, insulin resistance and impaired lipid metabolism. PMID- 2260212 TI - Serum cobalamin concentration in tuberculosis. A study in the Guinea savanna of Nigeria. AB - The concentration of serum cobalamin (SB12) was estimated in tuberculous Nigerian patients so as to define the role of this vitamin in the pathogenesis of the anaemia of tuberculosis. Complete data in 147 infected subjects before and during treatment and in 50 asymptomatic blood donors revealed no significant difference between mean serum cobalamin (mean SB12) concentrations of patients of both sexes and the asymptomatic controls. No differences were demonstrated between mean SB12 of groups of patients subdivided on the basis of degree of anaemia. Moreover, there was no significant correlation between Hb and SB12. Mean SB12 was essentially similar in patients with localised (300.7 pmol/l) and disseminated (311.1 pmol/l) disease. In the 121 patients with pulmonary tuberculosis, mean SB12 of those with one affected lung (291.9 pmol/l) was not significantly different from those with infection of both lungs (303.5 pmol/l). Antituberculosis therapy did not cause a fall in mean SB12. This study does not provide evidence of any significant abnormality in serum cobalamin concentration in Nigerians suffering from localised or disseminated tuberculosis. There is, therefore, no rational basis for the widespread but costineffective practice of supportive oral or parenteral vitamin B12 therapy in the management of this disease. PMID- 2260213 TI - Oesophageal diseases diagnosed by upper gastrointestinal endoscopy in the eastern province of Saudi Arabia. AB - Upper gastrointestinal endoscopy was performed on 2982 patients who presented with symptoms and signs related to the upper gastrointestinal tract. Of all these patients, 743 (25%) had the pathology limited to the oesophagus with a normal stomach and duodenum. These 743 patients constituted the material for this study. Of all oesophageal diseases, the most frequent endoscopic diagnosis was mild or moderate oesophagitis occurring in 350 patients (47%). Hiatal hernia with oesophagitis occurred in 232 (31%), oesophageal varices in 87 (12%) and ulcerative strictures in 74 patients (10%). Further histopathological examination of oesophageal biopsies from the latter 74 patients confirmed oesophageal carcinoma in 27 (3.7%), ulcerative oesophagitis in 43 (5.8%) and tuberculous oesophagitis in 4 patients (0.5%). The endoscopic and pathologic findings of these patients are presented and discussed. PMID- 2260214 TI - Cancer occurrence in Vanuatu in the South Pacific, 1980-86. AB - In order to study the occurrence of cancer in the archipelago of Vanuatu (ex-New Hebrides) within the Melanesia region in the South Pacific, a pathology based study was carried out. A total of 269 pathologically confirmed cancer cases (118 male, 151 female) were recorded over a 7 year period (1980-1986). Cervical cancer was numerically the most important malignancy in females (25.2% of all female cancers). In males, liver cancer was the most commonly observed (14.4% of all male cancers). The most interesting feature was the high proportion of thyroid cancers, especially in females. It consisted of 12.1% of all cancers in female and 5.2% in male Melanesians in Vanuatu. PMID- 2260215 TI - Mondor's disease. Relationship to use of body girdle. AB - Ten Mondor's disease patients and twenty matched controls provided data for this prospective study of the relationship of Quetelet Index, breast size and the use of body girdle on the development of Mondor's disease. Comparison of the study group patients with the controls in terms of percentage excess over their ideal Quetelet Index, extent of overweight, breast cup size and habitual use of body girdle showed only statistically significant difference in the use of the body girdle. It is concluded that among our patients, extensive use of a body girdle by a mesomorphic, overweight and large breasted female increases the risk of Mondor's disease. PMID- 2260216 TI - Fatal maternal tetanus following premature rupture of membranes and retained dead fetus. AB - A fatal case of tetanus arising from premature rupture of membranes in a retained dead fetus is presented. The condition followed the vaginal insertion of some herbs by a local herbalist. The case illustrates the danger of anaerobic infection in the presence of intrauterine fetal death particularly when it is complicated by premature rupture of membranes. Undue vaginal manipulation as happened in this case is an additional hazard and should be avoided. PMID- 2260217 TI - Insulin-dependent diabetes mellitus in homozygous sickle-cell anaemia. AB - Concurrent sickle-cell disease and diabetes mellitus is rare. The first case of the co-existence of these two disorders to be identified in Nigeria, West Africa, is presented. PMID- 2260218 TI - Massive periosteal elevation. An unusual presentation in acute haematogenous osteomyelitis of the long bones in children. AB - Although periosteal reaction in acute haematogenous osteomyelitis is known to occur and is well documented, massive periosteal reaction is rare. Two children with copious periosteal reaction around the shafts of the long bones are presented. This could be a manifestation of staphylococcal osteomyelitis as blood culture grew Staphylococcus aureus in one of the cases. PMID- 2260219 TI - Problems of drug therapy of epilepsy in developing countries. AB - Unavailability of drug therapy to patients with epilepsy in developing countries is probably the most important obstacle to effective primary care of epilepsy in these countries. At the recent international Merritt-Putnam Symposium in New Delhi, poor availability of drug supply and poor access to drug therapy were identified as major constraints to availability of drug therapy. The extent and magnitude of the problems are examined in this communication and methods of improving drug therapy of epilepsy in developing countries are suggested. PMID- 2260220 TI - Vaccinated versus unvaccinated children: how they fare in first five years of life. AB - Twenty five children who had undergone their full course of childhood immunization schedule were compared with 25 children who did not have any vaccinations for a period of five years. Parameters for comparison were measles, pertussis, poliomyelitis, tetanus and tuberculosis. Out of the 25 vaccinated children, only one child had mild measles at 2 1/2 years while 4 had suspected whooping cough at different points of the study period but not clinically diagnosed as pertussis. Among the unvaccinated group, 2 died of measles before the age of 3 years while 11 others went down with measles during an outbreak in 1986. An unvaccinated child also died of tetanus within the study period. In this paper we advocate the total integration of every community in the ongoing Expanded Programme for Immunization in Nigeria. PMID- 2260221 TI - Foley catheter, a simple device for removal of oesophageal foreign bodies. AB - An oesophageal foreign body is a common mishap in children. Removal through oesophagoscopy is a standard procedure but where this facility is not available this rather common accident could pose serious problems. A foley catheter was used repeatedly for the extraction of smooth foreign bodies from the oesophagus without fluoroscopic control. The procedure is safe and could be used whenever oesophagoscopy is not available. PMID- 2260222 TI - [An assessment of the relative contribution of the processes of cellular proliferation, polyploidization and hypertrophy to the increase in liver mass at various stages in the postnatal development of rats]. AB - Changes in isolated hepatocyte dry mass, its ploidy and liver mass at different stages of the rat postnatal ontogeny were investigated. The determination of these processes and special calculation made it possible to estimate quantitatively a relative contribution of cell proliferation, polyploidization and hypertrophy, not associated with DNA synthesis to the increase in the liver mass at different stages of the rat development. During the first week after the rat's birth, its liver growth is provided by 61 and 39% with hepatocyte proliferation and hypertrophy, respectively. Between the 14th and the 21st days of development, when considerable functional changes occur in the rat liver, the contributions of proliferative and polyploidization processes, and of cell hypertrophy into the liver mass increasing are roughly identical. Later on, the contribution of cell hypertrophy into the liver growth is noticeably reducing to reach within 1-2 months only 1%. On this developmental stage the liver mass increment by 2/3 is provided due to cell proliferation and by 1/3--to its polyploidization. As a whole, the accelerated growth of the rat liver from the birth to sex puberty is described as follows: the contribution of processes of proliferation and polyploidization, and of cell hypertrophy correspond to 28, 30 and 42%, respectively; afterwards, the liver growth being retarded. Within the period from 2 to 6 months, the liver mass increase is provided mainly (up to 76%) by cell proliferation, the shares of polyploidization and cell hypertrophy being 8 and 16%, respectively. PMID- 2260223 TI - [A cytophotometric comparison of the age-related changes in the DNA and protein content in human atrial cardiomyocytes in heart diseases]. AB - A study was performed on the human auricle muscle cells which were isolated from biopsies obtained in clinics during operation on heart. The nuclear DNA and the total protein in the cytoplasm were revealed by means of the two consecutive tests: the Feulgen and naphthol yellow S staining. DNA and protein contents were determined by two wave-length scanning cytophotometry. It is ascertained that under mitral defects the investigated parameters exhibit a tendency to increase with age: the nuclear ploidy and total protein content in the cytoplasm rise simultaneously with the increase in nuclear and cellular volumes, the polyploidy reaching higher levels than in myocardium of people of the same age without heart disease. If a patient suffered from ischemia, the nuclear polyploidy increased more slowly than cell hypertrophy to reach the level near the natural age limits. PMID- 2260224 TI - [The relationship of damage to and death of ascitic tumor cells during starvation to the ATP and free calcium content in the cells]. AB - Ascite tumor cells EL-4 were incubated in conditions of energy starvation (Hanks salt solution with rothenone and without glucose) at 37 degrees C for 3 hours. Under these conditions, some structural cell damages appeared within the first hours: enlarging and flattening of the cells, blebbing, vacuolization of the cytoplasm, nuclear chromatin condensation. Later on, a share of cells with obvious damage decreased, whereas that of the cells stained with trypan blue (dead cells) much increased (up to 90% after a 3 hour incubation). The cellular ATP decreased abruptly (up to 10% of the control) during the first 10 minutes of starvation. Free Ca2+ concentration increased within 1 hour of incubation more than two-fold. The conditions promoting Ca2+ influx (ionophore A23187 + Ca2+ in medium) accelerated the damage and cell death. However, the increase in free Ca2+ concentration did not trigger any damage in the energy-starved cells, since in the Ca2(+)-depleted medium (no increase in free Ca2(+)-concentration) the development of damages was not prevented. The damage initiation was irreversible: the addition of glucose to cell suspensions after 0.5-1 hour of their incubation in energy-starved condition did not prevent the development of damage, while ATP content in these cells was much increased. PMID- 2260225 TI - [The transgenic characteristics of mice with the gene for the surface antigen of human hepatitis B virus. II. The inheritance of the transgene and its expression in the liver]. AB - The inheritance of the MT-1sAg transgene (a gene of the major envelope polypeptide of human hepatitis B virus under the control of the metallothionein I gene promoter) and its expression in mouse liver cells have been studied. The Mendel inheritance of the transgene for three generations of mice was established. The analysis of transgenic mouse F2 chromosomal DNA by the Southern hybridization revealed the tandem copy insertion of the MT-1sAg plasmid. The expression of the transgene in liver cells, both with MT-1 promoter induction by Cd++ and without it, has been observed. The decrease in mouse liver cell parts containing viral protein HBsAg was observed as well as a reliable decrease in the share of mice with detectable MT-1sAg expression in the liver during the ontogenesis. The MT-1sAg-transgenic mice may be useful for studying the human chronic HBsAg state. PMID- 2260226 TI - [A karyotype study of the Vero cell line cultured long term in a monolayer by static and roller methods]. AB - A cytogenetic investigation of Vero cells, before and after adaptation to the medium containing a cattle serum, was carried out by methods of differential chromosome staining. Under these conditions, both the modal number of chromosomes (from 58 to 55) and the karyotype structure, namely the copy number of normal chromosomes and the marker composition were shown to change. The Vero cell karyotype stability was studied in the continued culture by the static (50 passages) and roll-bottle (37 passages) methods. The quantitative changes (the rising percentage of diploid cells, and the change of cell fraction involving the modal number of chromosomes) were shown to occur in spite of the chromosome composition stability, which limits the time of using Vero cells as a substrate for preparation of vaccines. PMID- 2260227 TI - [The use of a polyethyleneimine substrate for culturing dissociated cells of the central nervous system]. AB - A new method of preparation of polyethylenimin substrate for cultivation of dissociated cells from different parts of the central nervous system is presented. The alcohol solution of polyethylenimin used for this substrate is easily prepared, needs no sterilization and can be stored unlimitedly. The substrate provides a good attachment, growth and differentiation of neurons and glial cells and possesses all the advantages of more expensive polyaminoacid substrates (polylysine, polyornithine). Our substrate is highly adhesive, displays good optical properties and no artefacts after histological and histochemical treatment. PMID- 2260228 TI - Three-dimensional interactive graphics for displaying and modelling microscopic data. AB - EUCLID is a three-dimensional (3D) general purpose graphics display package for interactive manipulation of vector, surface and solid drawings on Evans and Sutherland PS300 series graphics processors. It is useful for displaying, comparing, measuring and modelling 3D microscopic images in real time. EUCLID can assemble groups of drawings into a composite drawing, while retaining the ability to operate upon the individual drawings within the composite drawing separately. EUCLID is capable of real time geometrical transformations (scaling, translation and rotation in two coordinate frames) and stereo and perspective viewing transformations. Because of its flexibility, EUCLID is especially useful for fitting models into 3D microscopic images. PMID- 2260229 TI - Estimation of allowable errors for tilt parameter determination in protein electron crystallography. AB - A three-dimensional reconstruction of a thin protein crystal requires an accurate assignment of amplitudes and phases in the three-dimensional reciprocal space. This assignment depends upon the tilt parameters which are experimentally determined. A theoretical estimate is made of the tolerable error in the determination of tilt parameters as a function of resolution and crystal thickness. PMID- 2260230 TI - [Experimental studies on the stability of femoral head spongiosa in reference to a new type blade profile of a 130-degree angle plate]. AB - The fracture of the trochanter major during and after angle plate-osteosynthesis of pertrochanteric fractures in mind, we made a 130 degrees-angle plate for experimental investigations with an only 6 mm broad blade profile. Therefore the lateral femoral corticalis will be weakened much less. The question was, whether this blade would be stable enough in the spongiosa of the femoral head with regard to the stability of the osteosynthetic system. For this the two methods of osteosynthesis were exposed to dynamic stress. The investigations were done with bone specimens by right-left-comparison with the new plate on the one side and the well-known 130 degrees-angle plate on the other side. The results show, that the new blade with the narrow profile has rather the same stability in the spongiosa of the femoral head as the AO-angle plate. PMID- 2260231 TI - [Isolated dislocation in the distal radio-ulnar joint]. AB - Anatomy, injury-mechanism and classification will be illustrated with a casuistry of the rate isolated luxation of the ulnar head. Diagnosis is established clinically and with comparative X-rays. In our case the luxation was irresponsible in general anaesthesia and had to be succeeded by open reposition with temporary pin-fixation. Postoperatively a cast up to the upper arm is necessary for six weeks. With the removal of the plaster the wire pins also must be immediately withdrawn, as to evade complications like fatigue-breakage of the implanted material. With adherence to this therapeutic scheme operative treatment is not problematic and - by means of posttraumatic physical therapy - shows a good functional result. PMID- 2260232 TI - [Acetabular fractures--surgical versus conservative treatment]. AB - In this paper the results of operative and conservative intervention of acetabulum fractures are analysed. It was possible to re-examine 80 of 146 Patients after a period of 5.46 years in mean. 23 patients were treated by osteosynthesis. Time from accident to operation was 13 days in mean. Posterior wall fractures seemed to be the most frequent (classified by Letournel). Results were evaluated according to the following criteria: clinical status (classified by the scheme of Merle d'Aubigne), X-ray, and subjective well-being. In the surgically treated group total hip prosthesis had to be implanted in five patients because of aseptic necrosis of the femoral head, 52.9% of the patients in this group had good results. In the conservative treated cases no total hip prosthesis had to be implanted. 77.8% of the patients had good results. A main aspect is that the average age of the patients who underwent a treatment by osteosynthesis is lower although the fractures were more severe. PMID- 2260233 TI - [Corrective osteotomy of the femoral and tibial shafts using the interlocking nail]. AB - The indication for nailing a femur or tibia fracture has been extended by the method of interlocking up to the meta/diaphyseal zone. For the stabilisation of osteotomies in these regions, the nail was used in 19 cases of femur and 23 of tibia corrections between 1983 and 1988 in the Orthopedic University Clinic Berlin. The osteotomies were done with a small skin incision in open way. Although there were three infections, bone consolidation was succeeded in all but one patient with the planned axis. The first achieved gain in length could not be hold in five cases after removing the interlocking screws in order to give full weight bearing to the leg for callus formation. In situations of non-unions with wrong position or refracture of biologically troubled bones after plating the method of interlocking nail is stable and enables bone recovery after grafting by drilling. The possibility of early full weight bearing is a great advantage for the rehabilitation of patients, who had been suffering from delayed fracture healing before. The nail itself preserves the right position of the bone in two dimensions, even if there are not exact fitting osteotomy fragments, and the interlocking screws secure the shorter part of diaphysis against malrotation. PMID- 2260234 TI - [Skin lesions following the use of a tourniquet]. AB - In a questionnaire study including 44 AO-clinics in German speaking countries, we investigated frequencies and possible causes of skin lesions under the cuff occurring after surgery in a bloodless field. Though these lesions are hardly dealt with in the literature available, the number of legal claims made by patients for these lesions has significantly increased in recent years. What has to be clearly differentiated are the known changes deeply extending into the soft tissues we see in the tourniquet syndrome. The precise pathogenetic mechanisms of these lesions are unknown. The combination of fluid collecting under the cuff and pressure applied to the skin by the cuff seems to be a likely cause. The most important precautions for avoiding these skin lesions consist in correct application of the cuff and in sealing the edge of the cuff the way that at least distally it will be safely fluid-tight. Correspondingly, fluid must under no circumstances (disinfectants) be allowed to collect or pool between the operating table and resting parts of the body (sacral region!). Based on present knowledge it is not possible to safely avoid these typical skin lesions. Strict adherence to the precautions listed above and explained in more detail in the text should therefore lead to the rejection of legal claims brought in such instances. PMID- 2260235 TI - [The application of an electronic data processing system in surgical intensive care]. AB - To assure quality and progression of surgical intensive-care therapy appropriate equipment is mandatory to ensure documentation and quality-control. In our hospital data processing of any information concerning the patients treated in the intensive-care unit has become part of the daily routine. This paper presents and discusses the underlying concept. PMID- 2260236 TI - [The regenerative ability of the iliac crest following spongiosa removal in man- induction by phosphate ceramics? I]. AB - The starting point for the investigation of calcium phosphate ceramics is given by the bone regeneration, including osteoconduction, osteostimulation and osteoinduction. The amount of the autogeneic bone, which can be used for transplantation to induce the organo typical regeneration, is a small one. Calcium phosphate ceramics are used as bone substitute. The basic knowledge of clinical employment is summarized. A new model for investigation of bone regeneration is introduced. In part II the results will be discussed. PMID- 2260237 TI - [Partial causality in case of physician liability]. AB - The specific theories about causality related to the different branches of law do have importance in the politics of rules. In civil law and physician liability law as well the theory of adequacy is valid. This theory selects only certain conditions as legally effective out of the abundance of all existing conditions. In physician liability law it typically happens, that indifferent chains of cause and effect coincide, what matters is to distinguish one from another and according to conditions to determine the partial causality which has to be attributes to the physician. The example of the untreated peri-lunar luxation and subsequent lunar necrosis illustrates the legally effective problematic nature of two causes. PMID- 2260238 TI - [Locked posterior dislocation of the shoulder]. AB - Whereas anterior dislocation of the shoulder is very common, posterior dislocation occurs in less than 2% of all cases. The diagnosis of posterior shoulder dislocation - especially in locked position - is difficult. The exact knowledge of the position of the humeral head within the shoulder joint is extremely significant, as the following case shows. The posterior shoulder dislocation was primarily recognized and treated correctly, while radiographics after reduction were misinterpreted. In this paper diagnostic and therapeutic measures are described. PMID- 2260239 TI - Bovine lameness in Liverpool. PMID- 2260240 TI - Evaluation of real time B-mode ultrasound scanning for detecting early pregnancy in cows. AB - A real time B-mode ultrasound scanner with a 7.5 MHz rectal linear transducer was used in two trials to detect whether dairy cows, less than 25 days after insemination at standing oestrus, were pregnant. In the first trial 17 cows were inseminated on the same day, and their reproductive tracts were examined 14, 15, 16 or 17 days after insemination. All the cows were diagnosed accurately as either pregnant or not pregnant. In the second trial 22 cows were inseminated on the day of observed oestrus while 14 were observed at oestrus but not inseminated. The animals were kept as a mixed group and an experienced operator scanned the uterus of each cow on one occasion, without knowing either the dates of observed oestrus or which cows had been inseminated. The rate of correct diagnosis was only 33 per cent in cows up to 16 days after oestrus, but increased markedly after 17 days and was 100 per cent by day 20. PMID- 2260241 TI - CCPP: antibodies to F38 polysaccharide in Mali goats. PMID- 2260242 TI - Comparative efficacy of praziquantel, albendazole, febantel and oxfendazole against Moniezia expansa. PMID- 2260243 TI - Ante mortem inspection. PMID- 2260244 TI - Transmission of BSE to a pig. PMID- 2260245 TI - Pet health insurance. PMID- 2260247 TI - Live exports of food animals. PMID- 2260246 TI - Adverse reactions to vaccine. PMID- 2260248 TI - Mortierella wolfii abortion in British cows. PMID- 2260249 TI - Cystotomy for treatment of urolithiasis in a hamster. PMID- 2260250 TI - Medical dissolution and prevention of canine and feline uroliths: diagnostic and therapeutic caveats. AB - Medical protocols designed to promote the dissolution of canine and feline struvite uroliths, the dissolution of canine ammonium urate and cystine uroliths and the prevention of all major types of canine and feline uroliths have been developed. However, because the causes of different types of uroliths vary, the medical protocols for their dissolution and prevention also vary. When the diagnosis of the underlying causes of uroliths becomes the rule rather than the exception, therapeutic failures should become the exception rather than the rule. PMID- 2260251 TI - A questionnaire survey of the prevalence of scrapie in sheep in Britain. AB - An anonymous, self-administered questionnaire has been used in two independent surveys to try to determine the prevalence of scrapie in the national sheep flock. The disease was recorded in 35 counties in England and Wales. About a third (26.5 and 37.3 percent) of respondents owning 100 or more sheep indicated that they had seen sheep with scrapie in their flocks. The incidences of clinical cases recorded in affected flocks in the two surveys were 0.5 and 1.1 cases/100 ewes/year. At present there is no control over the disposal of these animals. If as has been suggested, an increase in the prevalence of scrapie was a contributory factor in the emergence of bovine spongiform encephalopathy, it would seem logical that measures should be introduced to monitor the prevalence and incidence of scrapie and to control the disposal of clinical cases. PMID- 2260252 TI - Confirmation by Doppler echocardiography of valvular regurgitation in a horse with a ruptured chorda tendinea of the mitral valve. AB - Regurgitation of blood through the left atrioventricular valve owing to the rupture of one of the chordae tendineae of the valve was diagnosed in a horse with sudden-onset respiratory distress and a holosystolic cardiac murmur. Severe regurgitation was confirmed with Doppler echocardiography and prolapse of part of the valve leaflet was identified with B-mode ultrasonography. The rupture of one of the chordae tendineae of a right accessory cusp of the left atrioventricular valve was confirmed post mortem. Bronchiolitis, multifocal haemorrhages and haemorrhagic fibrous plaques were found in the pleura of the dorsocaudal segments of the lungs. PMID- 2260253 TI - Intestinal cryptosporidiosis in calves on a dairy farm. AB - Oocysts of Cryptosporidium species were identified in the faeces of scouring calves from a dairy farm. The faeces were watery and greenish yellow but the calves were usually alert and not desiccated when they were admitted to the clinic. Without treatment they became severely desiccated and recumbent within a few hours, but after symptomatic treatment they improved rapidly. The importance of cryptosporidiosis as a herd health problem is discussed. PMID- 2260254 TI - Illegal sales of medicines. PMID- 2260255 TI - Temptation of the fast buck. PMID- 2260256 TI - Disease in young pheasants. PMID- 2260257 TI - Veterinary manpower crisis. PMID- 2260258 TI - Outbreak of anthrax in pigs. PMID- 2260259 TI - Corynebacterium pseudotuberculosis in milk of CL affected goats. PMID- 2260260 TI - Dystocia in Friesian heifers. PMID- 2260261 TI - Peritonitis in adult horses. PMID- 2260262 TI - Ergotism in young cattle. PMID- 2260263 TI - A veterinary approach to leeches. AB - Leeches have had a long association with human beings and in recent years have proved valuable in biomedical research and surgery. Veterinary surgeons should be concerned with these creatures because of their role in causing disease, because of the part they may play in controlling the numbers of other invertebrates, because of their potential in veterinary therapy and because of the need to manage them properly in captivity. PMID- 2260264 TI - Experimental conjunctival infection of lambs with a strain of Chlamydia psittaci isolated from the eyes of a sheep naturally affected with keratoconjunctivitis. AB - Five ram-lambs were inoculated into the left conjunctival sac with the 15R isolate of Chlamydia psittaci, recovered from a sheep with keratoconjunctivitis. A sixth ram-lamb was kept in contact with them. The five lambs developed varying degrees of acute conjunctivitis and 14 days later C psittaci could be recovered from the inoculated eyes, from which Branhamella ovis was also isolated. The eyes were examined regularly for four months; C psittaci could not be re-isolated but the eyes developed varying degrees of follicular conjunctivitis. After four months the sheep were treated with corticosteroids in an attempt to reactivate a latent chlamydial infection but no chlamydiae could be isolated. Five months after the start of the experiment the six lambs were inoculated with 15R into the left conjunctival sacs. Acute conjunctivitis developed which was not as severe as after the first inoculation, but C psittaci could only be recovered from the left eyes of three sheep three days after inoculation. The eyes remained chronically affected by follicular conjunctivitis. Six months after the start of the experiment the left eyes were again inoculated with 15R; on this occasion acute conjunctivitis did not develop and chlamydiae could not be isolated. Chronic follicular conjunctivitis persisted until the experiment was terminated three months later. PMID- 2260265 TI - Account of three outbreaks of malignant catarrhal fever in cattle in the Republic of Ireland. PMID- 2260266 TI - Field investigation of anthelmintic resistance of small strongyles in horses. PMID- 2260267 TI - Occurrence of S typhimurium DT204c in poultry in England and Wales. PMID- 2260268 TI - Echinococcosis as a public health problem. PMID- 2260269 TI - Sale or supply of animal medicines by veterinary surgeons. PMID- 2260270 TI - Summer mastitis caused by Pasteurella haemolytica. PMID- 2260271 TI - Treatment for bromocyclen poisoning. PMID- 2260272 TI - Myasthenia gravis in a dog. PMID- 2260273 TI - Tortoises and hibernation. PMID- 2260274 TI - Species-specific DNA probes for Campylobacter species isolated from pigs with proliferative enteritis. AB - Cloned, chromosomal DNA probes from porcine isolates of Campylobacter hyointestinalis and C. mucosalis were developed for the detection and identification of these putative swine enteric pathogens. High molecular weight chromosomal DNA from each species was used to construct genomic libraries in plasmids. Recombinants were selected which hybridized strongly to the homologous organism, but not to any other species of Campylobacter. Species-specific recombinants were labeled with phosphorus-32 and tested for sensitivity by dot blot hybridization to various dilutions of DNA and bacteria from each swine species, including C. hyointestinalis, C. mucosalis, C. coli and C. jejuni. Specificity was tested by hybridizing these probes against various strains of C. hyointestinalis or C. mucosalis, and against reference strains of all other described Campylobacter species. A C. hyointestinalis-specific probe and a C. mucosalis-specific probe were identified which were capable of detecting 1 ng of DNA or 10(4) cfu by bacterial spot blotting on nylon membranes. These probes hybridized to intestinal mucosal scrapings containing C. hyointestinalis and C. mucosalis obtained from pigs with proliferative enteritis, but not to material from normal pigs. Thus, cloned, chromosomal DNA probes may be useful in the detection and identification of bacteria involved in swine proliferative enteritis. PMID- 2260275 TI - Comparison of a DNA probe, complement-fixation and indirect immunofluorescence tests for diagnosing Anaplasma marginale in suspected carrier cattle. AB - Most estimates of the prevalence of anaplasmosis have been based on serologic data using the complement-fixation (CF) and/or card agglutination tests. Since these tests are considered to be only about 50 percent reliable for detecting carrier cattle in enzootically stable herds, the need for more sensitive diagnostic tests is widely recognized. The objective in the present study was to compare the sensitivity of the CF test with that of the indirect immunofluorescence (IIF) test and a recently developed DNA probe in determining the prevalence of Anaplasma marginale infection in cattle from an enzootic area. The study herd consisted of 52 8-month-old steers and 13 3-year-old cows of mixed beef breed. All cattle were initially tested for this comparative purpose. All but one animal (one that was a positive reactor as assessed by all three tests, and served as a positive control), were treated with long-acting oxytetracycline in an attempt to clear any carrier infections. Each animal was then retested at 1 month and 2 months post-treatment (PT), in an effort to determine if the DNA probe could be used to evaluate the effectiveness of the drug. Six of the 65 (9.2%) initial serum samples were CF positive. In contrast, 60 (92.3%) and 64 (98.5%) of the samples were positive as assessed with the IIF test and the DNA probe, respectively. The DNA hybridization reactions varied in intensity within the sample population indicating different individual levels of infection. The DNA probe hybridized with two samples taken at 1 month PT, and with two different samples taken at 2 months PT. The mean IIF titers were reduced at both the 1 month and 2 month sampling times. These results suggest that the drug did not eliminate infections in all cattle. Some may have been cleared, but, in any event, the drug did reduce the level of infections below the sensitivity of the DNA probe and interrupted continuity of stimulation of antibody. Therefore, the DNA probe and the IIF test appear to be considerably more sensitive in detecting carrier infections than the CF test, and should be considered in future epidemiologic studies. PMID- 2260276 TI - Development of a recombinant Anaplasma marginale DNA probe. AB - An Anaplasma marginale DNA probe has been developed by using an improved method for the isolation of genomic DNA. Purified genomic A. marginale DNA from the St. Croix isolate was partially digested with Sau 3A1 into fragments (greater than or equal to 5.0 kb). The restriction fragments were cloned using standard techniques in the pBR322 vector and used to transform E. coli (DH5) host cells. The recombinant A. marginale DNA library was screened by the colony lifting procedure. Colonies containing plasmids with A. marginale DNA inserts were identified by hybridization with a genomic A. marginale DNA radiolabeled probe (32P). Seven recombinant A. marginale DNA probes were evaluated by dot-blot in vitro hybridization assays to identify candidates as diagnostic tools in bovine anaplasmosis studies. Specificity and sensitivity experiments were carried out by using heterologous and homologous DNAs. The heterologous panel contained bovine DNA (WBC) and blood parasites DNA from Babesia bovis (Bb), Babesia bigemina (Bbi), Eperythrozoon suis (Es) and Eperythrozoon wenyoni (Ew). The homologous DNA panel included A. marginale DNAs of 12 different isolates which were isolated in the Caribbean, Mexico, and the U.S.A. The selected diagnostic probe was identified as pSt. Croix A1, and labeled with 32P by using in vitro nick translation and random primer techniques. The pSt. Croix A1 probe demonstrated 100% specificity and high sensitivity by hybridization in dot blotting and Southern blotting. The probe can detect 500-1000 infected erythrocytes per microliters which corresponds to a parasitemia of less than 0.01%. The A. marginale DNA insert was approximately 6.4 kb in size and a partial restriction map has been constructed. PMID- 2260277 TI - Immunoperoxidase staining for the detection of autoantibodies in canine autoimmune skin disease; comparison to immunofluorescence results. AB - Skin sections from 22 dogs with autoimmune skin disease were stained with anti canine IgG, IgM and IgA using an immunobridge immunoperoxidase method. Eight cases of lupus erythematosus, three cases of pemphigus vulgaris, and 11 cases of pemphigus foliaceus were included. Results of previously performed, direct immunofluorescence tests for the detection of canine immunoglobulin on skin were available on 17/22 cases. The immunoperoxidase method yielded an overall positive result in 59% (5/8 lupus erythematosus, 2/3 pemphigus vulgaris and 6/11 pemphigus foliaceus) versus an overall positive result of 47% for direct immunofluorescence (3/5 lupus erythematosus, 2/2 pemphigus vulgaris and 2/10 pemphigus foliaceus). The immunobridge immunoperoxidase method compared favorably to direct immunofluorescence testing of canine skin for autoantibody in cases of lupus erythematosis and pemphigus vulgaris, and was superior in cases of pemphigus foliaceus. This method should prove useful as an aid in the diagnosis of canine autoimmune skin disease. PMID- 2260278 TI - Preliminary data on efficacy of Mycoplasma gallisepticum vaccines containing different adjuvants in laying hens. AB - Chickens were vaccinated subcutaneously twice, at 13 and 17 weeks of age. The vaccines used were the whole organisms of Mycoplasma gallisepticum (MG) adjuvanted with multilamellar positively charged (MPC) liposomes or oil-emulsion. Other chickens received the same bacterins but supplemented with Salmonella typhimurium cell wall protein mitogen (STP) (50 micrograms/dose). At 21 weeks of age, each bird was challenged in the right and left caudal thoracic air sacs. The challenge dose/chicken was 1.3 x 10(5) CFU of MG (R-strain). A significant immunoglobulin (Ig) response specific to MG was observed in sera of chickens collected 3 weeks after the first and second vaccination with MG adjuvanted with MPC liposomes or oil-emulsion. The same two treatments had highly significant MG titers in eggs collected during the first and second month post challenge. Both groups had highly significant protection (P less than 0.05) against MG transmission in eggs layed during the first month post challenge. Vaccination with MG organisms adjuvanted to MPC liposomes or oil-emulsion resulted in higher egg production, during the first month following challenge, in comparison to the unvaccinated-challenged birds; the same two groups had higher egg production in the second month following challenge compared to unvaccinated-challenged birds, but not significantly different (P greater than 0.05). The addition of STP to bacterins containing MG organisms adjuvanted to MPC liposomes or oil-emulsion, resulted in a significant reduction (P less than 0.05) of the Ig-specific to MG in sera and in a significant drop in egg production (P less than 0.05) during the first month following challenge. PMID- 2260279 TI - Fate and uptake of soluble and particulate antigens in the preparturient bovine mammary gland. AB - Pregnant heifers were infused intramammarily with ovalbumin in one quarter and killed S. uberis in another quarter. The animals were slaughtered at time intervals after infusion, and tissues were collected from different parts of the gland and from the local lymph nodes. Ovalbumin and bacteria reached the lymph nodes as early as 1 and 3 h after infusion respectively. Ovalbumin was also present in blood 5-10 min after infusion and in non-infused quarters. Both ovalbumin and bacteria were phagocytosed by the epithelium of the mammary gland. However, bacteria were seen in the tissues in small numbers at all stages after infusion. Larger numbers were phagocytosed by neutrophils in the lumen of ducts, 18 h after infusion. Phagocytosis of both ovalbumin and bacteria was not present in the connective tissue of the gland. The results indicate increased permeability of the preparturient gland to soluble proteins, but limited uptake of bacteria. Furthermore, a mechanism of transfer of antigens among quarters has been suggested. PMID- 2260280 TI - Mycoplasma bovis suppression of bovine lymphocyte response to phytohemagglutinin. AB - The effect of viable Mycoplasma bovis on the in vitro bovine peripheral blood lymphocyte response to phytohemagglutinin (PHA) was studied. Results showed that M. bovis did not act as a mitogen for bovine lymphocytes. Viable M. bovis produced a dose and time dependent suppression of the PHA stimulated lymphocyte response. Suppression was not a result of differences in the viability of infected or control lymphocyte cultures. The suppressive effect of M. bovis was found to be independent of the concentration of PHA used in the test and the lymphocyte response could not be restored by supplementation of the culture medium with arginine. Delay for 48 h after PHA stimulation before adding M. bovis to the lymphocyte cultures diminished, but did not prevent, the suppression of the lymphocyte response. These results show that suppression of the lymphocyte response does not require the presence of M. bovis during the period of PHA stimulation, and that M. bovis was capable of interrupting [3H]-thymidine incorporation in lymphocytes which were actively synthesizing DNA. PMID- 2260281 TI - Natural killer cell activity of chicken intraepithelial leukocytes against rotavirus-infected target cells. AB - Intraepithelial leukocytes (IEL) and splenocytes collected from uninfected and rotavirus-infected chickens were evaluated for cytotoxic activity against a natural killer (NK) cell-susceptible lymphoblastoid cell line (LSCC-RP9) and against rotavirus-infected chick kidney cells in 4-h chromium-release assays. Both splenocytes and IELs from uninfected and rotavirus-infected chickens were cytotoxic for LSCC-RP9, and the levels of this NK cell activity were not altered by infection of the host with rotavirus. IELs but not splenocytes from uninfected and rotavirus-infected chickens were cytotoxic for rotavirus-infected but not for uninfected chick kidney cell targets. Because this cytotoxic activity was not induced nor altered by rotavirus infection of the host, and was not major histocompatibility complex-restricted, it was considered to be due to NK cell activity. The cytotoxicity of IELs against rotavirus-infected target cells was dose-dependent; however, there was some suppression of cytotoxic activity at high effector to target cell ratios. There were no differences in the cytotoxic activities of IELs collected from the duodenum versus the jejunum. The in vitro cytotoxic activity of IELs against rotavirus-infected target cells suggested that NK cell activity may be an important immune response to rotavirus infections in vivo. The absence of cytotoxic activity by splenocytes against rotavirus-infected target cells indicated that there may be different subpopulations of NK cells in the spleen and intestinal epithelium of chickens. PMID- 2260282 TI - Vitamin A deficiency impairs cytotoxic T lymphocyte activity in Newcastle disease virus-infected chickens. AB - The effect of vitamin A deficiency on cytotoxic T lymphocyte (CTL) activity was investigated during the acute phase of disease 7 days after primary inoculation and 1 day after secondary inoculation in chickens with or without Newcastle disease virus (NDV, La Sota strain) infection. Day-old chickens with limited vitamin A reserves were fed purified diets containing either marginal (ad libitum) or adequate (pair-fed) levels of vitamin A, and at 3 weeks of age half of the chickens in each group were infected with NDV. Cytotoxic activity was investigated during the acute phase of disease (7 days after primary inoculation) and 1 day after secondary inoculation, in an assay system with either peripheral blood lymphocytes (PBL) or nonadherent splenocytes as effector cells and adherent splenocytes from the same animal as target cells. After primary inoculation, cytotoxic activity could only be demonstrated in nonadherent splenocytes. Vitamin A deficiency resulted in significantly reduced CTL activity at all effector/target cell ratios tested. After reinfection CTL activity could also be demonstrated in PBL, but only from chickens fed the control diet, suggesting a diminished pool of CTL in vitamin A deficiency. The results of this study indicate that vitamin A deficiency impairs CTL activity - a part of the cell mediated defense system - and this may have important implications for recovery from viral infection. PMID- 2260283 TI - Effect of milk or colostrum on phagocytosis of glass- or plastic-adherent Streptococcus agalactiae by bovine granulocytes. AB - In the presence of milk, bovine polymorphonuclear cells (PMN) assumed a polarized shape, a feature of motile cells, and their adherence to plastic was augmented. Milk enhanced the phagocytosis of glass- or plastic-adherent Streptococcus agalactiae. In contrast, PMN were not stimulated by colostrum. PMID- 2260284 TI - Sources of supply of selected immunobiologics, 1990. PMID- 2260285 TI - Adult respiratory distress syndrome during pregnancy and immediately postpartum. AB - From 1976 to 1983, the adult respiratory distress syndrome occurred in 14 patients during pregnancy or within a month postpartum. There were 8 survivors, giving a 43% mortality. All but 2 patients had obstetric-related precipitating events--labor problems, infections, eclampsia-toxemia, and obstetric hemorrhages. During emergency cesarean sections, 3 patients had respiratory problems that may have caused their respiratory distress syndrome. The average duration of mechanical ventilatory support was 16 days. Six patients had barotrauma with 1 patient sustaining an irreversible anoxic central nervous system injury. Infections were documented in 8 patients, 6 of whom had obstetric foci. There is a lack of information regarding the adult respiratory distress syndrome in this patient group. Though uncommon, it can cause substantial mortality and morbidity. PMID- 2260286 TI - Recent trends in cesarean section use in California. AB - Cesarean section use in the United States has increased to 24.7% of deliveries in 1988 and is the most common hospital surgical procedure. California cesarean section rates were examined to measure recent trends in obstetric practices and to project future patterns of cesarean section use. Using discharge abstracts from 1983 to 1987 California hospital deliveries, total cesarean section rates were found to increase from nearly 22% in 1983 to 25% in 1987, an increase of 15%. Using a series of least-squares regression models, time trends in the distribution of indications associated with cesarean section among all deliveries and indication-specific cesarean section rates were evaluated. Increases in the number of women with previous cesarean section and fetal distress contributed to rising cesarean section rates. In addition, indication-specific cesarean section rates increased for breech presentation and dystocia. These trends were counterbalanced, in part, by declining rates of repeat cesarean sections. Trends noted for July 1985 through 1987 did not differ substantially from those observed for January 1983 to June 1985, suggesting that recent policy attempts to alter cesarean section use have not had a measurable effect on existing trends. Projections suggest that California cesarean section rates will rise to a level of 34% by the year 2000. PMID- 2260287 TI - To strike or not to strike? House-staff attitudes and behaviors during a hospital work action. AB - Work actions by house staff are an infrequent response to sometimes difficult working conditions, but they can have a notable effect on institutional cohesiveness and represent a challenge to traditional notions of medical ethics. To determine the extent of participation in a hospital-wide doctors' strike and factors associated with participation, we surveyed 432 house officers at a university-affiliated public hospital where a contract dispute had recently led to a 4-day work action. Of 257 respondents, 69% approved of the strike and 50% participated in it. Both strikers and nonstrikers agreed that quality of care and specific contract issues were important precipitants of the event. By logistic regression, factors independently associated with strike participation (P less than .05) included being unmarried, training in internal medicine or psychiatry, being in earlier stages of training, being assigned to an outpatient service at the time of the strike, holding a favorable view of physician activism, and perceiving nurses, faculty, peers, and the public to have favored the strike. These associations may provide a basis for understanding the individual and social determinants of house-staff strike activity. PMID- 2260288 TI - Peer review in scientific journals--what good is it? PMID- 2260289 TI - Chlamydial infections. PMID- 2260290 TI - Brachial plexus birth injury. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in neurosurgery. 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, research workers, or scholars to stay abreast of these items of progress in neurosurgery 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 Neurosurgery of the California Medical Association, and the summaries were prepared under its direction. PMID- 2260291 TI - Implanting fetal tissue to treat Parkinson's disease. PMID- 2260292 TI - Endoscopic neurosurgery. PMID- 2260293 TI - Implantable neurosurgical drug delivery systems. PMID- 2260294 TI - Interstitial radiotherapy for malignant glioma. PMID- 2260295 TI - Management of prolactin-secreting pituitary adenomas. PMID- 2260296 TI - Surgical treatment of petroclival meningiomas. PMID- 2260297 TI - Intraoperative digital subtraction angiography for neurosurgery. PMID- 2260298 TI - Irritable children. PMID- 2260299 TI - Surgical treatment of spasticity. PMID- 2260300 TI - Use of high-dose glucocorticoids in acute head and spinal cord injuries. PMID- 2260301 TI - Warning leaks and subarachnoid hemorrhage. PMID- 2260302 TI - A 38-year-old man with painful, dependent ankle edema and clubbing. Hypertrophic osteoarthropathy syndrome. PMID- 2260303 TI - Ethics, jurisprudence, and economics in the medical school curriculum. AB - Medical ethics, medical jurisprudence, and medical economics are recognized as important components of a medical school curriculum. These subjects were introduced through a course given at the University of California, Davis, School of Medicine. Four aspects of the format and content of the course were instrumental to its success. Teaching principles of medical ethics within the context of jurisprudence and economics permitted the students to gain an understanding of the institutions and processes that act as positive and negative constraints on physicians' clinical and professional behavior. The course was offered during the fourth year following required clinical rotations so that all aspects of the course could be based on the clinical experiences of the students. It was presented in a continuing medical education format away from the normal teaching environment of first- and second-year classrooms and third-year clerkships. Finally, the course was designed by a multidisciplinary, multidepartmental planning group that included students. PMID- 2260305 TI - Modern technology and unaffordable costs. PMID- 2260304 TI - Diagnostic tests should be used for sexually transmitted chlamydia. PMID- 2260306 TI - Are SI units dangerous? PMID- 2260308 TI - An occupational hazard. PMID- 2260307 TI - Ciprofloxacin-induced anaphylactoid reactions in patients infected with the human immunodeficiency virus. PMID- 2260309 TI - [Alpha 1-antitrypsin phenotypes and their role in the development of early and late cirrhosis of the liver]. AB - On the basis of cooperation with the Children's Health Centre the role was analysed of certain phenotypes of alpha 1-antitrypsin (alpha 1-AT), mainly Pi Z and Pi MZ phenotypes in the development of infantile cirrhosis. A significant participation was demonstrated of the latter phenotype in patients developing infantile cirrhosis. The preliminary analysis of the incidence of pathological alpha 1-AT phenotypes in the group of patients with cirrhosis manifested at the adult age seems to indicate the higher incidence of the Pi MZ phenotype as compared with the general population. The genetically determined low serum alpha 1-AT activity is probably one out of many factors determining the development of this disease. Further studies will be aimed at explaining whether the combination of action of two factors: alpha 1-AT deficiency and exposure to hepatotoxic agents is not accelerating the appearance of the disease and is not potentiating its clinical intensity. PMID- 2260310 TI - [Treatment of anemia with animal blood preparation "Livex" in children with pyelonephritis]. AB - The results are presented of anaemia treatment during pyelonephritis in 20 children with the preparation obtained from animal blood livex. The preparation was administered for eight weeks. After the treatment of a statistically significant rise was observed of haematocrit and haemoglobin concentration. No adverse effects of the preparation were observed. PMID- 2260311 TI - [Effectiveness of peritoneal dialysis using dialysis fluid of modernized composition]. AB - In six patients with terminal renal failure the effectiveness was assessed of intermittent peritoneal dialyses (IPD) using the dialysing fluid of modernised composition. On the basis of the obtained results the values were calculated of the total sodium (TMTNa) and potassium (TMTK) elimination glomerular filtration rate, and the sodium elimination index. The values were calculated of the dialysing clearance of urea, creatinine, potassium, and inorganic phosphorus. The correlations were analysed between the dialysing clearance of studied substances and the body area of patients, the duration of dialysis, and glomerular filtration rate. The results were compared with the effectiveness of peritoneal dialysis carried out with the dialysing fluids of formerly used electrolyte composition. PMID- 2260312 TI - [Preparation of health personnel for the promotion of breast feeding--a pilot study. (Part I--the level of knowledge)]. AB - The study is a part of a preliminary analysis of the situation before introducing the promotion program of breast-feeding. It concerns the assessment of the knowledge of lactation physiology and properties of human milk among health service workers employed in mother and child health care. Significant deficiencies of knowledge on this subject were found. The obtained information was used for outling the directions of indispensable training. PMID- 2260313 TI - [Calcium antagonists and the digestive system]. PMID- 2260314 TI - [Laboratory diagnosis of renal changes caused by occupational chemical factors]. AB - The problem of early detection of the consequences of toxic action of chemical substances on the kidneys at the working place is becoming one of more important problems in the prophylaxis of renal diseases. The introduction of new sensitive diagnostic methods such as enzyme activity determination or low-molecular-weight proteins measurement in urine has made possible detection of renal damage in the reversible stage. As yet the observations demonstrate that workers exposed in their occupation to heavy metals (cadmium, lead, metalic mercury) and organic solvents should be subjected to special control for detection of renal changes. PMID- 2260315 TI - [Immunological aspects of Giardia intestinalis infection]. PMID- 2260316 TI - [Rehabilitation treatment after surgical reconstruction of the Achilles tendon]. AB - Calcaneal tendon called Achilles tendon is mechanically the strongest tendon of human organism. Thanks to its specific situation (just under the skin) and to its basic role in the biomechanics of walking the calcaneal tendon is exposed especially in sports to excessive tensions and strains which may lead to chronic inflammatory states and even ruptures. In the paper the methods of surgical treatment are outlined which are used in the pathology of calcaneal tendon and in particular the principles of rehabilitation treatment starting from the first days after the operation. PMID- 2260317 TI - [A case of osteopoikilosis]. AB - On the basis of literature and own observation a very rare form is discussed of skeletal system anomaly--osteopoikilosis+ which is considered to be a genetically determined, benign skeletal dysplasia. It manifests itself with numerous spotty densities of bony structure situated usually near the joints of long bones. They may be erroneously regarded as malignant metastases. The reported case of osteopoikilosis+ conformis the hereditary character of the disease. PMID- 2260318 TI - [The Peutz-Jeghers syndrome]. AB - A case is described of the Peutz-Jeghers syndrome in a 28-year-old female patient. The patient was treated surgically for intussusception of small intestine caused by polyp. PMID- 2260319 TI - [A case of the treatment of a patient with infected femoro-popliteal transplant by continuous flushing with antibiotic solution]. PMID- 2260320 TI - [Rare location of metastases of testicular cancer]. PMID- 2260321 TI - [A case of rare location of accessory breasts]. AB - A case is presented of a 42-year-old female patient operated on for accessory mamillae situated in anterior axillary folds. These changes were excised and the clinical diagnosis was confirmed by microscopic examination. The postoperative course was uneventful. PMID- 2260322 TI - [Familial occurrence of central diabetes insipidus]. AB - Two cases are presented of familial diabetes insipidus with analysis of pedigree involving four generations. The analysis of diabetes insipidus occurrence in this family indicates the autosomal dominant type of inheritance. PMID- 2260323 TI - [Erythrocyte morphology in asymptomatic microhematuria: experimental studies and clinical significance]. AB - Renal and postrenal origin of hematuria can be differentiated by analysis of the morphology of the erythrocytes in the urinary sediment. In order to investigate the mechanisms which cause the membrane changes in dysmorphic erythrocytes, indicating renal origin of bleeding, normal red blood cells were exposed in vitro to an osmotic environment similar to that of the nephron. Upon exposure of osmotically challenged erythrocytes to a hemolytic environment, 50 to 90% of the cells became dysmorphic in a time- and dose-dependent manner and were indistinguishable on light and electron microscopy from those obtained in vivo from a patient with proven glomerular microhematuria. The reliability of erythrocyte morphology in differentiating between renal and postrenal microhematuria was evaluated by performing microscopic analysis as the initial step in the investigation of 316 consecutive patients. In 123 patients with eumorphic red cells in their urine complete urological investigation revealed a postrenal source of bleeding in 85%. Out of 193 patients with dysmorphic erythrocytes, 132 were followed up for at least 2 years after only minimal diagnostic evaluation. An additional postrenal source of bleeding developed in two patients, which was easily diagnosed by the change in erythrocyte morphology. Our studies, representing experience over 6 years with asymptomatic microhematuria, show that microscopic examination of erythrocyte morphology as initial diagnostic step is a safe, inexpensive and efficient method which renders invasive investigations superfluous in the majority of patients. PMID- 2260324 TI - [Treatment results and andrological follow-up in orchitis due to mumps]. AB - This paper reports the results on 13 patients with mumps orchitis, with special consideration of 7 andrologically after-cared cases. The results with and without therapeutic use of corticosteroids are compared. Furthermore, we present the andrological outcome in these patients. PMID- 2260325 TI - Fulminating gallbladder cancer presenting as leptomeningeal carcinomatosis and acute renal failure. AB - We report a case of clinically undiagnosed gallbladder cancer presenting as leptomeningeal carcinomatosis and showing a fulminant clinical course with acute renal failure due to ureteric obstruction by carcinoma metastasis. A review of the literature fails to demonstrate a similar case. PMID- 2260326 TI - We are humanitarians first. PMID- 2260327 TI - The power of coalition politics. PMID- 2260328 TI - Does it pay to be honest? PMID- 2260329 TI - Factious AIDS: a case presentation and review of the literature. PMID- 2260330 TI - Consent problems and the Southeast Asian refugee. AB - More than 24,000 refugees of Southeast Asian descent live in Wisconsin. These people, of a different cultural background with different methods of treating the sick, on occasion seek medical aid. It is incumbent on the treating physicians to understand the cultural differences and the avenues open to them to render treatment to these people. This paper reviews these concerns. PMID- 2260331 TI - The costs of smoking in Wisconsin: a silent epidemic. PMID- 2260332 TI - Global estimates for health situation assessment and projections 1990. PMID- 2260333 TI - Effect of naproxen and sulindac on blood pressure response to atenolol. AB - Twenty-eight patients with mild to moderate essential hypertension well controlled by atenolol entered a five-week, double-blind, placebo-controlled trial of the effects of sulindac and naproxen on blood pressure (BP) control. Atenolol alone was administered during weeks 1, 3, and 5. Naproxen or sulindac was administered with atenolol during week 2, with crossover during week 4. Data were analyzed for 27 of the patients (one dropped out after developing a skin rash). Naproxen significantly increased the systolic BP compared with placebo (mean 4.0 mm Hg; 95 percent confidence interval, 1.1-7.0; p less than 0.05). There were no significant differences in systolic BP during sulindac administration compared with placebo or naproxen. No significant effects on diastolic BP were observed. Weight was increased by naproxen and sulindac compared with placebo (mean 0.6-0.8 kg, p less than 0.05), although not to a clinically significant extent. One-week therapy with naproxen has a greater potential than sulindac to increase systolic BP in well-controlled hypertensive patients receiving atenolol; however, the increase is minor and unlikely to be of clinical significance. PMID- 2260334 TI - Increased 6-hydroxycortisol excretion in pregnant women: implication of drug metabolizing enzyme induction. AB - The effect of pregnancy on hepatic drug-metabolizing enzyme activity was investigated in nine healthy pregnant women using the ratio of 6-hydroxycortisol (6-OHF), to total 17-hydroxycorticosteroid (17-OHCS) in 24-hour urine as an index of the hepatic monooxygenase activity. The values of 6-OHF and the ratio (713 +/- 250 micrograms/d and 0.323 +/- 0.242; mean +/- SD) before delivery were significantly higher than they were during early puerperium (395 +/- 145 micrograms/d and 0.114 +/- 0.055) and approximately three months after delivery (237 +/- 67 micrograms/d and 0.066 +/- 0.034). Although the values three months after delivery were comparable to those found in the nonpregnant group (n = 10; 228 +/- 48 micrograms/d and 0.081 +/- 0.031), 6-OHF values one week after delivery were significantly higher than those observed in the control group. These observations suggest that drug-metabolizing enzyme induction may occur during pregnancy. PMID- 2260335 TI - Outcome of cholesterol screening in a community pharmacy. AB - The purpose of our study was to determine if a community pharmacist could affect total blood cholesterol (TBC) of ambulatory patients by a program of education, consultation, and cholesterol screening. Of 241 initially screened individuals, 57 patients with TBC greater than 5.17 mmol/L (greater than 200 mg/dL) met the inclusion criteria of this six-month study. Of these, 51 completed the study. Outcome was determined by changes in TBC measured during the initial screening and after two follow-up visits. Pharmacist intervention included obtaining TBC concentrations and reporting the results to patients, teaching patients about the role of cholesterol in illness and health, explaining risk factors associated with cardiovascular disease, and providing follow-up communication with patients. Data were analyzed using ANOVA, Mann-Whitney, and chi-square. The mean TBC was 5.84 mmol/L (225.7 mg/dL) for the study group and 4.23 mmol/L (163.8 mg/dL) for participants with TBC less than 5.17 mmol/L (less than 200 mg/dL (p less than 0.0001). There was a significant difference (p = 0.0124) in mean age for the study group (36.4 years) versus other participants (30.0 years) but no difference in distribution by gender (p = 0.18). ANOVA showed significant differences in TBC during the three visits (p less than 0.0001). There was a significant decrease in mean TBC concentrations between visits 1 and 2 and between visits 1 and 3 (p less than 0.0001), but no difference between visits 2 and 3 (p = 0.48). Compared with mean baseline values, 81.4 and 72.6 percent of the patients had a decline in TBC at visits 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260336 TI - Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction. AB - Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation. PMID- 2260337 TI - Intravenous streptomycin. AB - Streptomycin is an effective drug for the treatment of tuberculosis. It is currently recommended for use only by the intramuscular route. This method of drug delivery is accompanied by considerable pain which is unacceptable to many patients. With the advent of many improvements in intravenous therapy that have occurred in the past 40 years, reevaluation of the intravenous use of this drug is warranted. We describe the short-term use of intravenous streptomycin in four patients with pulmonary tuberculosis. PMID- 2260338 TI - Cerebellar syndrome caused by isoniazid. AB - Treatment of tuberculosis in a hemodialysis patient with isoniazid, rifampin, and pyrazinamide resulted in the development of acute cerebellar dysfunction. This resolved rapidly following the discontinuation of isoniazid and pyrazinamide, reinstitution of isoniazid at a lower dose, and addition of pyridoxine. We discuss why we believe this syndrome was caused by isoniazid. Patients with renal failure who undergo antituberculous therapy with isoniazid should receive supplemental pyridoxine to reduce the likelihood of isoniazid-related neurotoxicity. PMID- 2260339 TI - Excipients in valproic acid syrup may cause diarrhea: a case report. AB - A 5-year-old child receiving valproic acid syrup for seizure control developed diarrhea probably from the excipient ingredients. Each 5 mL of valproic acid syrup contains sucrose 3 g, glycerin 0.75 g, and sorbitol 0.75 g, providing daily amounts of 36, 9, and 9 g of sucrose, glycerin, and sorbitol, respectively. The diarrhea resolved when the child was switched to another valproic acid product. Clinicians should be aware of potential problems that may occur from excipient ingredients in pharmaceutical products when evaluating adverse effects of medications. PMID- 2260340 TI - The pharmacist as a health consultant--ten years later. AB - Pharmacists remain a readily accessible and trusted source of information about health. In order to assess the quality of counseling on health matters and the progress of the profession in this activity over the last decade, a study similar to one reported in 1978 was conducted. We visited 46 community pharmacies and requested advice from the pharmacists concerning the proper treatment of an infant with diarrhea. Interviewers volunteered no additional information, but questions asked by the pharmacist were answered according to a predetermined hypothetical case involving an 18-month-old infant with diarrhea and vomiting. Findings include the following: approximately one-third of the pharmacists recommended a product without caution and less than 20 percent inquired about fever, nausea, vomiting, diet, or the infant's condition. We believe pharmacists should approach health counseling with an increased awareness of the harmful potential in providing inappropriate medical information. PMID- 2260341 TI - Use of influenza vaccine in AIDS patients. PMID- 2260342 TI - Verapamil in the treatment of schizophrenia. PMID- 2260343 TI - Antibiotic prophylaxis in cesarean section. AB - Several controversies exist regarding the use of antibiotic prophylaxis in cesarean section. Studies have investigated effectiveness, choice of drug, timing, duration, and appropriate route of administration. Efficacy of antibiotic prophylaxis in preventing postoperative endometritis in certain high-risk patients has been well documented. Factors identifying patients at high risk for endometritis include: indigent socioeconomic status, labor prior to cesarean section, rupture of chorioamniotic membranes, and number of vaginal examinations. Although many different antibiotics have been tested, no particular regimen has been found to be superior. Administration of antibiotics after cord clamping reduces the risk of fetal exposure without compromising maternal risk of endometritis. A single dose of ampicillin or a first-generation cephalosporin (e.g., cefazolin or cephalothin sodium) given intravenously provides adequate prophylaxis. No additional benefit has been demonstrated with the use of multiple dose regimens. PMID- 2260344 TI - The potential for mental status changes associated with systemic absorption of anticholinergic ophthalmic medications: concerns in the elderly. AB - Several cases have been reported of anticholinergic toxicity following the administration of commonly used parasympatholytic cycloplegics and mydriatics. Cases have been reported in children, adults, and the elderly. The risk of developing mental status changes secondary to anticholinergic ophthalmic medications is of particular concern in the elderly. Drug-induced mental status or behavior changes should not be mistaken for exacerbation of an underlying disorder or the onset of a new disease (e.g., Alzheimer's disease, dementia). Clinicians should be aware of these potential complications, monitor for changes in mental status, and take appropriate action. PMID- 2260345 TI - Griseofulvin: a new look at an old drug. AB - Griseofulvin is the oral antifungal agent of choice for the treatment of dermatophytoses. This article reviews the history, pharmacokinetics, adverse reactions, and traditional therapeutic applications of griseofulvin. In addition, reports since 1960 of the use of the drug in the treatment of Raynaud's phenomenon, progressive systemic sclerosis, lichen planus, mycosis fungoides, herpes zoster, eosinophilic fasciitis, and molluscum contagiosum are discussed, noting the varying degree of therapeutic success. PMID- 2260346 TI - Soft tissue calcification in renal failure. AB - Disorders of phosphorus, calcium, and vitamin D are common in patients with renal failure. Medical management, including dietary phosphorus restriction, administration of phosphate binding agents, and calcium and vitamin D sterol supplementation, must be instituted to control serum concentrations of these substances because of the loss of normal homeostatic mechanisms. If these measures are not employed, soft tissue calcification and hyperparathyroidism may result. We report the case of a 22-year-old woman with endstage renal disease treated with continuous ambulatory peritoneal dialysis who developed secondary hyperparathyroidism and tumorous calcinosis as a result of noncompliance with dietary phosphorus restriction and phosphate-binding agent therapy. The etiology and treatment of soft tissue calcification in patients with renal disease are discussed. Compliance with dietary restrictions and phosphate binding agents is frequently problematic in this population. Pharmacists should play an active role in educating patients with renal disease on the consequences of noncompliance with dietary and drug therapy. PMID- 2260347 TI - Fluconazole: a new triazole antifungal agent. AB - Fluconazole is a fluorine-substituted, bis-triazole antifungal agent. Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes. Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models. Fluconazole can be administered both orally and intravenously. Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively. Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89. Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug. Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts. Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis. Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available. Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole. Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin. Rifampin appears to decrease metabolic clearance of fluconazole. Fluconazole is available as oral and parenteral formulations. Once-daily doses of 100-400 mg are recommended. Dosage reduction is advised for patients with impaired renal function. PMID- 2260348 TI - Prescribing and dispensing practices for oral iron tablets: a Canadian experience. AB - The formulation of an oral iron tablet may influence its therapeutic efficacy in correcting iron deficiency. In order to determine the oral iron preparations patients in a Canadian urban center were receiving, a questionnaire was circulated to family physicians, internists, surgeons, and obstetrician gynecologists to determine their prescribing practices. A survey of pharmacies in the city was also conducted to determine which brand of each iron salt (sulfate, gluconate, fumarate) they dispensed for a generic oral iron prescription. Most physicians (74 percent) chose ferrous sulfate as their drug of first choice. The majority of prescribers would not specifically request either enteric-coated/slow release or nonenteric-coated preparations as first or second choices (71 and 64 percent, respectively). Enteric-coated or slow-release preparations were specified by 10 and 19 percent of physicians as first and second choices, respectively. Most pharmacies (96 percent) dispensed an enteric-coated preparation of ferrous sulfate for a generic prescription. We believe that many patients are receiving iron tablets with altered release properties (enteric coated/slow-release). These tablets may fail to provide the desired therapeutic benefit based on the known physiology of iron absorption. PMID- 2260349 TI - The Saskatchewan program for rational drug therapy: effects on utilization of mood-modifying drugs. AB - In 1978, the Joint Committee on Drug Utilization (JCDU) was appointed by the Saskatchewan Minister of Health to identify and analyze concerns related to drug use and to recommend appropriate methods for dealing with such concerns. Emphasis was placed on the quality of healthcare in the province and on the provision of information as a basis for education of the public and health professionals. Since 1978, 14 committee reports providing drug utilization statistics and specific recommendations for improving drug therapy have been distributed to Saskatchewan health professionals. The main focus has been on utilization studies of "mood-modifying" drugs (analgesics, minor and major tranquilizers, sedative/hypnotics, stimulants, and antidepressants). The JCDU initiated a program whereby drug profiles of certain patients were released to selected health professionals. Individuals who received daily doses in excess of JCDU guidelines for mood-modifying drugs over a three-month period were categorized as extreme users. Patient medication profiles of their drug use were forwarded on a quarterly basis to physicians who prescribed and the primary pharmacy that dispensed mood-modifying drugs to these patients. From the time of the first profiles (October-December 1979) until 1983, there was a 15 percent decrease in the number of extreme users. Between 1977 and 1985, there was a decrease in the percentage of the overall population receiving any prescriptions for these drugs (from 20 to 17.4 percent). PMID- 2260350 TI - Fighting tuberculosis with old weapons. PMID- 2260351 TI - Fluconazole success after amphotericin B and flucytosine failure in cryptococcal meningitis. PMID- 2260352 TI - Endpoints for usage of cardiac drugs. PMID- 2260353 TI - Possible hemolytic anemia associated with human insulin therapy. PMID- 2260354 TI - Assessment of pediatric theophylline measurements. PMID- 2260355 TI - SCAMC: a meeting of the "computer" minds. PMID- 2260357 TI - Medication(?)--not drug. PMID- 2260356 TI - Considerations in establishing expiration dates for fluphenazine decanoate multiple-dose vials. PMID- 2260358 TI - Comment: clinical education in Rhode Island. PMID- 2260359 TI - Comment: neurologic toxicity related to ciprofloxacin. PMID- 2260360 TI - Comment: aminoglycoside volume of distribution in children. PMID- 2260361 TI - [Acute pancreatitis--etiology, pathological anatomy and pathogenesis]. AB - Acute pancreatitis is a disease characterized by abdominal pain, low-grade fever, abdominal tenderness and rigidity, and moderate elevation of the white blood cell count. A widely used revised classification of pancreatitis is that proposed in 1984 at Marseille. It only distinguishes between acute and chronic pancreatitis. In 61 cases were 40 men and 21 women. The mean age in the total series was 52.5 years. The etiology of the acute condition was alcoholism in 32.8% and biliary tract disease in 23%. In 9.8% the acute pancreatitis is associated with alimentary tract diseases (adipositas, hyperlipidemia). The severity of acute pancreatitis is pathological anatomy determined by three stages. In pathogenesis the process of digestion is caused by activated pancreatic enzyme with acinar cell injury. The acinar cell is normally protected from the action of its own enzymes by elaborate intracellular compartmentation of enzymes. Acute pancreatitis is triggered by pancreatic phospholipase A leading to necrosis of lipolytically active fat cells with release of membrane-toxic fatty acids with following destruction of adjacent tissue. Fat necrosis initiates an acute inflammatory reaction with immigration of granulocytes and liberation of kinins, which activate pancreatic enzyme. Pancreatic enzymes are similar to lysosomal enzymes with regard to substrate specificity. Activation will be also triggered by lysosomal enzymes of necrotic acinar cells. PMID- 2260362 TI - [A densitometric method for the assessment of myocardial perfusion using digital subtraction angiography]. AB - The aim of the method presented is the quantitative description of the perfusion of the myocardium. In the framework of the invasive diagnostics of the coronary heart disease with catheterization of the left heart, ventriculography and coronarography in Seldinger's technique in 50 patients (35 of them well to be evaluated) subsequently DSA-investigations of the left coronary artery (LCA) were performed by means of the DVI-2 CV system (Philips) and densitometrically evaluated with the help of the analytic processing unit (APU). In injection by hand of 4 and 6 ml, respectively, visotrast 370 in each case 10-15 DSA-pictures in LAO 60 degrees-projection were possible. For a differentiated evaluation the total myocardium was subdivided into 12 partial areas. The densitometric analysis consisted in the calculation of time-density curves over all areas and their description by suitable parameters: density maximum (DMAX) and its moment TMAX, elevation of the curve SLOPE at 50% of DMAX, the elevation time AZEIT as well as measure for the exponential decrease of the curve after the maximum LAMBDA. For special questioning the parameters of the 12 areas were concentrated according to the main supply areas of the anterior interventricular branch (RIVA), the circumflex branch (RCX) and the apex of the heart, respectively. In the interobserver comparison the statistical analysis of the results showed deviations lower than 10% (except LAMBDA). Significant correlations were found between the body-weight and the applied quantity of contrast remedies, respectively, and the parameters DMAX and AZEIT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260363 TI - [Incidence in myocardial infarct and mineral content of the drinking water]. AB - In the district of Wernigerode with circa 105,000 inhabitants in the framework of a "myocardial infarction register" obligatory for the GDR during 10 years (from 1 July 1973 to 30 June 1983) all persons were registered who suffered a myocardial infarction according to the criteria of WHO, and furthermore all those patients who suddenly died before the arrival of the alarmed physician or on the way to hospital. In 3,013 cases of infarction the incidence of the infarction at the specific residence of the patient with 648 investigations of the hardness of water in a period of 10 years is compared to the study 138 investigations of the hardness of water with 138 watering places of the individual towns. The determinations of the hardness of water which regularly took place already before 1973 were regularly performed twice a year. The specific incidence and the hardness of water were compared. The level of the potassium, calcium and magnesium content in the drinking water of hard water and soft water districts was compared and the effects of a deficiency above all of magnesium on the mineral balance of man was explained. PMID- 2260364 TI - [Diabetes mellitus and development of kidney insufficiency]. AB - With respect to the great number of diabetics in our population and the development of renal insufficiency as a fatal complication at diabetic patients (15-25% of chronic haemodialysis patients suffer from diabetes mellitus) we examined diabetics of a rural district. We registered a total of 1164 diabetics: 690 of them showed normal renal function while 405 patients had serum creatinine in threshold values and 69 patients' serum creatinines exceeded 120 mumol/l. The age of onset and the duration of diabetes mellitus, its type and the metabolic control, furthermore symptoms of proteinuria, hypertension, obesity and retinopathy were registered in relation to renal function. The duration of diabetes, the metabolic control, proteinuria turned out to be prognostically important factors. PMID- 2260365 TI - [Non-medicinal therapy tachycardiac arrhythmias]. AB - The conservative antiarrhythmic treatment was improved by the introduction of the Holter-ECG technique, of the serial electrophysiological testing and by new antiarrhythmic drugs. An essential enhancement of the therapeutic possibilities, particularly when ineffectiveness, proarrhythmic action or intolerance of the medicaments are existing, are increasingly the non-medicamentous techniques of the antiarrhythmic therapy. Thus the treatment of arrhythmia has become by far more effective, but at the same time also more complicated and more expensive. Between 1980 and 1989 altogether 53 patients were treated with anti-tachycardiac pacemakers (25), with an ablation of the bundle of His by means of catheter mediated DC-shock application (20), with a direct surgical interruption of the bundle of Kent (5) as well as with the implantation of an automatic cardioverter/defibrillator (3). Indications, techniques and results of the individual methods are represented. PMID- 2260366 TI - [Basic program for the diagnosis of arterial hypertension]. AB - The diagnostic step-program in arterial hypertension can be divided in a so called basic program and in special differential-diagnostic programs. The basic evaluation for every hypertensive subject contains family and personal history, clinical investigation, blood pressure measurement, electrocardiogram, chest X ray, blood tests (creatinine and potassium) and urine analysis. The extended basic program enables the evaluation of global cardiovascular risk. Furthermore other blood and urine examinations (including vanilmandelic acid), fundoscopy, echocardiography and sonography of the kidneys are of particular value for determining severity and etiology of the disease. After this program an extension of diagnostics can be renounced in about 90% of hypertensives. PMID- 2260367 TI - [The scientific basis and evaluation of the present-day concept of risk factors and their significance for the prevention of chronic non-communicable diseases]. AB - Chronic diseases increased in their significance, to them first of all belong cardiovascular diseases. They particularly restrict a further increase of the life-expectancy of the persons older than 40 years. In the judgement of the development of these groups of diseases during the last decades the so-called concept of risk factors was developed, which obtained particular significance for the myocardial infarction and the chronic cardiovascular diseases. Though the epidemiologic investigations up to now could cover only correlations and not causal connections, the latter - that means causal conditions - seem to get an increasing support by results of the adequate basic research. Still more impressionable is, however, the regression of the mortality due to cardiovascular diseases which took place during recent years in connection with the changes of the living habits in several countries of the earth. From the results of our own research the particular urgencies concerning the preventive medicine in our country are described which must consist in changes of the living habits, in particular of the habits of nutrition and the abuse of coffee, tea, tobacco, alcohol, etc., moreover also in personal behaviour. Independent of this genetic factors certainly play a decisive part. Apart from the individual strategy mass strategic aspects will obtain a greater importance in the following years. PMID- 2260368 TI - [Basic program for the diagnosis and therapy of inflammatory diseases of the kidney]. AB - The specialist for general medicine and for internal medicine, respectively, in the primary consultation must express the suspicion of the occurrence of a renal disease on the basis of the anamnesis and the findings of the clinical examination and confirm or exclude it by simple diagnostic tests. It is entered into the individual test component in diagnostics. The securing of the diagnosis, the judgement of the renal function as well as differential-therapeutic considerations for the further care are to be performed by the results of the diagnostic steps II (basic diagnostics, in special questionings by step III). About 100,000 patients with renal diseases are country-wide cared for at present, in whom 11% already suffer from a renal insufficiency. It is referred to the most important recommendations for therapy in bacterial and glomerular renal diseases. PMID- 2260369 TI - [Diagnostic predictive value of C-reactive protein and expectant management of patients with premature rupture of the membranes]. AB - To evaluate the predictive diagnostic value of CRP in a wait-and-see management of PROM 110 courses of labour and childbed with 114 babies were investigated with respect to both complications of mother and newborn. Complications during childbed could only be seen in 2.7%, 3.4% of the newborns suffered from septic disease. With regard to complications of newborns and mothers mediated by infection, CRP was demonstrated to have a prepartum sensitivity of 79% in combination with a specificity of 80%. The absolute highest sensitivity and specificity of CRP were found at a cut-off point of about 14 mg/l, which is clearly above the normal level of 6 mg/l serum. In almost 50% of the cases with maternal antepartum CRP levels up to 20 mg/l no pathogenic bacterial invasion could be revealed in the newborn. CRP therefore can be taken as an additional parameter in the management of PROM even in cases treated with corticosteroids due to its specificity and indicates better than WBC and polys when to terminate the wait-and-see attitude. PMID- 2260370 TI - [Cesarean section in multiple pregnancy especially with triplets and quadruplets- preparation and execution]. AB - The frequency of multiple pregnancies has increased in perinatal centers during the last years. The result is a rise in perinatal risk. Because of prematurity and abnormal presentations and positions, cesarean section rate is high in this group. This paper discusses the intra- and perioperative problems that may occur in cesarean section of multiple pregnancies, advices are given for perioperative management. In the discussion of surgical techniques, the amnion preserving incision according to Hillemanns is described as a reliable procedure, especially in multiple pregnancies combined with prematurity. PMID- 2260371 TI - Determination of serum copper concentration in pregnancy at term, using potentiometric stripping analysis (P.S.A.). AB - The serum copper concentrations were determined in a group of 41 pregnant women and in a group of 30 non-pregnant women used as a control-group. The determinations were made by Potentiometric Stripping Analysis (P.S.A.) a method much cheaper but equally reliable to others used for determination of bioelements. The levels of copper in serum were found significantly lower in both groups [control group: (mean +/- S.D.): 0.56 +/- 0.16 mg/l, pregnant women, (mean +/- S.D.): 1.77 +/- 0.47 mg/l] than the levels referred in studies from other countries. This finding in combination with the obvious advantages of the P.S.A. method, allow us to propose copper determination as a routine examination during pregnancy, in order to make an early diagnosis and manage a possible copper deficiency in pregnant women, accordingly. PMID- 2260372 TI - [Peridural anesthesia and method of delivery. Peridural anesthesia performed by the obstetrician]. AB - In deliveries in epidural analgesia (PDA) there are more obstetrical operations than in deliveries without PDA. We have investigated the delivery mode in relation to the indication of epidural analgesia. If the PDA is done because of prolonged course of labour or because of suspicious fetal heart rate, about 40% of these women deliver spontaneously, in about 35% a cesarean is done, and in about 25% a forceps- or vacuum-extraction is done. This high rate of operative interventions is not unexpected due to the indication that led to epidural analgesia. If the PDA is done because of painful labour only, 60% of these mothers deliver spontaneously, 12% by cesarean and about 28% by forceps or vacuum. The rate of vaginal extractions is triple as in all obstetric patients of the clinic. The increase of operative deliveries in PDA isn't found generally. Epidural analgesia managed by the obstetrician doesn't result in more complications by the method itself, the increase of operative deliveries is found even in clinics where the PDA is carried out by the anesthetist. The possible reasons are discussed. PMID- 2260373 TI - [Persistent cysts of the choroid plexus as sonographic indications of a genetic defect]. AB - In the case of a 29-year-old woman an early SGA (small for gestational age) fetus was detected in her third pregnancy. This fact being already a possible indicator for a genetical defect, the fetus also showed permanent cysts of the Plexus choroideus as a sonographical symptom of a deletion of the chromosome 10 (10 qter). The value of Plexus choroideus cysts sonographically diagnosed during pregnancy is discussed by showing the differential diagnoses, the clinical proceedings in general and specially the indications for a chromosomal analysis. PMID- 2260374 TI - [Potentials in the elderly]. PMID- 2260375 TI - [Potentials in old age: personal and social processes of their development]. AB - In developed societies, antecedents of and conditions for the development of older people's potentials are favorable. Longevity and wellbeing have increased through progress in hygiene, medicines economy, and ecology. Nevertheless, potentials of the elderly are a neglected theme in the media, in social policy, and in scientific discourse. Along with Riley and Riley's statement that individual potential is outrunning the social potential, it is argued that aging persons have indeed developed potentials, while institutions and society have contributed little. Institutionalization rather seems to veil the potentials of the elderly and to disregard their manifestations. Potentials of the elderly are described as abilities to realistically perceive chances and limitations of life in old age, reappraise life after experiencing loss, and accept expressed in sympathy for children and grandchildren, in sharing their concerns, and taking responsibility for human and social issues in life. Older people can develop potentials, which allow them to focus less on many of their own needs and to invest energies and commitment in persons, ideas, values, or activities that can continue beyond their own lifetime. PMID- 2260376 TI - [Development of intelligence in old age]. AB - This article attempts to find the structure of a selected spectrum of intelligence. A combination of longitudinal and cross-sectional methods is applied. Two dimensions were found, which can be named as "crystallized" and "fluid" abilities (in the sense of Horn & Cattell). Whereas, the crystallized abilities do not show any systematic variation from age 61 to 83, fluid abilities decline with age. Schaie's three-component-model is not able to describe differences and variations of crystallized intelligence. Within fluid intelligence, age changes are more important than cohort differences. There are hints that structural changes take place. PMID- 2260377 TI - [Future research perspectives of a psychoanalytical gerontopsychophysiology- personality and the aging process]. AB - Based on the irreversibility of physiological development during the aging process, a concept of permanent personality development throughout life is presented, which is at no time completed. Based on clinical experience, questions are induced for future research in the field of gerontopsychosomatics, which take into consideration the possibility of a revival of previously existing neurotic conflicts as well as possible new functional and psychosomatic symptoms understandable because of the actuating situation in old age. The question is raised whether such newly acquired psychosomatic symptoms must be considered as a multimorbidity aspect in older people and thus not accessible to adequate therapy. Finally, the concept "personality plasticity" and "life-long personality development" are related to one another. Gerontological research has emphasized time and again that in older and aged persons competences persist. It is the objective of the present paper to present a perspective, supported by empirical studies, to those who may be unduly impaired for a time in their potential by symptoms or conflicts. PMID- 2260378 TI - [Motor activity--healthy development--aging successfully?]. AB - Human science has re-discovered the human body. We hardly realize, however, how much a person really depends on his body. This article intends to make evident how the close relationship between motor activity, feeling, thinking, and social behavior can be utilized for the healthy development of young people and for keeping fit and healthy in old age. Examples from the fields of therapy and rehabilitation illustrate the working of motor activity when there are physical, psychic, and social deficiencies. If sports for the elderly is practiced in order to improve the process of successfully aging, we have to reconsider this subject, and we must integrate sports for the elderly into health routines. This will challenge physical education teachers and exercise program directors and they should prepare for the future. PMID- 2260379 TI - [Cognitive and activity-oriented processes in the rehabilitation of elderly stroke patients]. AB - Investigated were 12 aged stroke patients during and one-half year after treatment in hospital; interviews are compared with regard to stress, competence, and coping. The analysis shows that patients become aware of multiple restrictions after their release from hospital. We pointed out that rehabilitation should concentrate more strongly on normal life demands of the patients as well as on their psycho-social resources. A survey of some of the typical coping strategies is included, which could be considered during the rehabilitation process. PMID- 2260380 TI - [Care requirements or the insufficient consideration of the potentials and competences of sick elderly persons]. PMID- 2260381 TI - [Potentials in old age--also a political task]. AB - Growth of potentials in the elderly can be promoted by political measures. It is an essential task for politicians to perceive the potentials in the elderly, support public initiatives for the elderly, and support maintenance of independency. Gerontological contributions important for politics for the elderly are discussed. Political measures are recommended. PMID- 2260382 TI - [The competency model of old age: possibilities in clinico-psychiatric interpretation exemplified by a history group (oral history group)]. AB - Regardless of the increasing prevalence of gerontopsychiatric diseases the increase of age-related treatments is only gradual. Due to the deficit centered image of elderly patients, which impairs the physician-patient interaction, the proper perception of cognitive and social competences of these patients within the clinical routine is impeded. To start a first approach to an age-related treatment format in regard to the "assets" of elderly patients an "oral history" group was established in a general psychiatric ward that stressed topic-related autobiographical memories of daily life occurrences. The author proposes that elderly patients who attempt to give an age-related contribution within the social framework of a general psychiatric ward feel better about their illness. PMID- 2260384 TI - Will National Data Bank encourage litigation? PMID- 2260383 TI - [Empirical studies on the performance of elderly automobile drivers]. AB - Before the year 2000 the number of elderly drivers (65 years and older) in the Federal Republic of Germany will probably double. Concerns about traffic safety predominate-under the broadly accepted assumption that the elderly drive less cautiously. The most important results of driving tests of elderly drivers (and a comparison group of middle-aged) and their relation to performance measures are presented. The results show that the elderly drivers performed worse in laboratory tests, but in driving tests (in a significant number of different traffic situations) they did not differ unfavourably from the middle-aged drivers. PMID- 2260385 TI - Hewing to the CPT-4. How to avoid a Medicare postpayment audit. PMID- 2260386 TI - Patient access to medical records: answers to ten common questions. PMID- 2260387 TI - Liver transplantation in Virginia. AB - Survival rates ranging from 70-80% have been documented over the past three years in liver transplant patients at the Medical College of Virginia. Survival declined in patients with numerous complications of chronic liver disease and with significant deterioration in hepatic synthetic function. Early referral was a major factor contributing to survival. PMID- 2260388 TI - Mapping out skin cancer: Mohs micrographic surgery. PMID- 2260389 TI - Compulsory medical education: the downside. PMID- 2260390 TI - Avoidable claims in the liability experience of Virginia FPs insured by the reciprocal. AB - In response to the threat of litigation, physicians practice defensive medicine. A more effective means of reducing malpractice liability and improving the quality of patient care is to practice defensible medicine, i.e., those practice patterns that reduce the potential for claims and increase the likelihood that when claims do arise, they can be successfully defended. Unlike hospital-based specialists, family physicians can directly influence a significant portion of their risk of suit. By focusing management time and attention on the factors in their office practices that are linked to malpractice claims activity, family physicians can reduce the likelihood of being involved in claims. PMID- 2260391 TI - Safeguards against suit. PMID- 2260392 TI - Injured Infant Act. PMID- 2260393 TI - Explain. PMID- 2260394 TI - [The outlook for evolutionary physiology (from the viewpoint of the historian of science)]. PMID- 2260395 TI - [The concept of universal functional modules and the further development of the theories of the biosphere, ecosystems and biological adaptations]. PMID- 2260396 TI - [Does an evolutionary kinship exist between the chemosignal systems of eukaryotes and prokaryotes?]. PMID- 2260397 TI - [Modern concepts of the structural evolution of the nervous system exemplified by the vertebrate visual system]. PMID- 2260398 TI - [The limbic system and the problem of the evolution of the vertebrate hindbrain]. PMID- 2260399 TI - [Sensory receptors: the evolution of the ionic environment of the receptor membrane]. PMID- 2260401 TI - [Capacity of erythroid progenitor cells of the human bone marrow for clonal growth in diffuse chamber culture]. AB - The ability of human marrow erythroid progenitors growth in diffusion chamber culture has been assessed. Chambers containing cells (2 X 10(5)) suspended in clot were implanted into peritoneal cavity of anemic rats. The anaemia was induced by phenylohydrazine (50 mg/kg body weigh). Erythroid colonies were counted on day 1, 2, 3, 5, 7, 9, 11, 13 and 15. Two types of colonies formed by erythroid progenitors (BFU-D-E, CFU-D-E) were determined using criteria of colony size and culture duration. The count of colonies formed by CFU-D-E was highest on day 2 (29 +/- 4) and underwent reduction in subsequent days. Colonies formed by BFU-D-E were seen beginning of day 5 and their number peaked on day 7 and 9. These results indicate that the best time for determining the growth of human marrow CFU-D-E and BFU-D-E in diffusion chamber culture is on day 2 and day 7-9, respectively. PMID- 2260400 TI - Acute lymphoblastic leukemia in children below two years of age. AB - From among 1464 children with ALL 167 (11.4%) at diagnosis had two or less than two years, 53 of them were infants. Most of them had a great tumor bulk, 15 had initial CNS infiltration and 31 WBCc greater than or equal to 100000/ML. 66 were treated according to St. Jude or LSA2L2 programs (the I group), 101 according to BFM programs (the II group). Complete remission was obtained in 85% of patients. In 63 children relapses occurred in the course of treatment whereas in 5 after the therapy cessation. In majority of cases, there were isolated relapses, mostly, they involved bone marrow. CNS involvement was found, in both mixed and isolated relapses, in 28 children (20%). 64 children are alive, in 43 of them the therapy was stopped. Kapla-Meier estimates for event free survival (EFS) after 8 years were 19 +/- 4.7% in the first group vs 37.38 +/- 6.3% in the second group. Due to therapy intensification the treatment results have been improved (p = 0.05) but still they are not satisfactory, particularly in case of infants and children with WBC greater than or equal to 100000/ML. Analysis of the lot of children showed that apart from age at ALL diagnosis and the initial WBC the methods of treatment are also the prognostic factors. PMID- 2260402 TI - [Tumor necrosis factor/cachectin]. PMID- 2260403 TI - [The role of HLA antigens class II in differentiation of normal and pathological B-lymphocytes. I. Normal hematopoiesis]. PMID- 2260404 TI - [The role of HLA antigens class II in differentiation of normal and pathological B-lymphocytes. II. HLA-D expression in leukemia and non-Hodgkin's lymphoma]. PMID- 2260405 TI - [Intravenous administration of deamino-D-arginine-vasopressin (DDAVP) to patients with hemophilia A and von Willebrand's disease]. AB - Following an intravenous infusion of DDAVP in a single dose of 0.3 microgram/kg b.w. and subsequent infusion of 4 g of epsilon-aminocaproic acid, 28 tooth extractions have been performed in 18 patients with mild haemophilia A and 5 patients with type I von Willebrand's disease. During the subsequent 7-10 days, the patients received epsilon-aminocaproic acid orally. In 89% of cases the healing was uneventful and no bleeding complications occurred. A single infusion of DDAVP and epsilon-aminocaproic acid was also effective for the management of muscle hematoma ++ and haemarthroses in 4 of the 7 mildly affected haemophiliacs. In the remaining 3, the symptoms of bleeding subsided following repeated infusion of DDAVP. The results indicate that a single intravenous infusions of DDAVP when combined with the administration of antifibrinolytic agents can insure sufficient haemostasis after tooth extraction and is useful for the management of muscle hematoma and hemarthroses in patients with mild haemophilia A mild von Willebrand's disease. PMID- 2260406 TI - [Clinical usefulness of blood platelets cryopreserved in liquid nitrogen]. AB - The hemostatic effectiveness of platelet concentrates cryopreserved in a vapor phase of liquid nitrogen were evaluated after transfusion of 14 concentrates to 6 patients. Transfusion of AB0 and Rh-compatible platelet concentrates elevated the number of circulated platelets in donors by about 24 G/L. The mean corrected count increment (C.I.) after 001 and 24 hours post transfusion was 14.694 and 7.735/microliters/m2/10(11) respectively. Decrease of haemorrhagic diathesis, and correction of bleeding time in all cases have been observed. PMID- 2260407 TI - [Prognostic value of the peroxidase index in patients with acute nonlymphoblastic leukemia]. AB - In 91 patients with acute non-lymphoblastic leukaemia the peroxidase index was determined in blast cells or promyelocytes in bone marrow. Complete remission was obtained exclusively in patients with the value of the index 0-9% or over 69%. The duration of the remission and the survival time were significantly longer in patients with a high peroxidase index. This index may be useful for prediction of the course of acute non-lymphoblastic leukaemia in adults and its high value is associated with better prognosis. PMID- 2260408 TI - [Heterogeneity of the cases of chronic B-cell leukemia and the heterogeneity of leukemic cell populations]. AB - In a group of 23 patients with chronic lymphocytic leukaemia in 1-4 clinical stages of the disease according to Rai et al (34) classification, mostly untreated (only 5 treated) considerable heterogeneity was found as evidenced by: variability of the morphological patterns of bone marrow, differences of immunological phenotypes of peripheral blood lymphocytes between individual cases, --coexistence of the features of maturity and immaturity in the populations of peripheral blood lymphocytes in the same case. PMID- 2260410 TI - [Neutrophils do not affect clonal growth of granulocyte progenitor cells cultured in vivo in diffuse chambers]. AB - The effect of polymorphonuclear leukocytes on the growth of granulocytic progenitors in the diffusion chamber culture (CFU-dG) has been studied. It has been shown that peripheral blood neutrophils do not affect the myeloid colony formation in this culture system. The inhibition of CFU-dG growth, observed in the presence of peripheral blood leukocytes was dependent on prostaglandins release from monocytes. PMID- 2260409 TI - [Relation between the duration of the chronic phase of chronic myeloid leukemia and total dose of busulfan in the first year of the treatment]. AB - The analysis was based on 31 patients with chronic granulocytic leukaemia (CGL) treated during the period 1975-1986 and the correlation between the total dose of busulphan administered during the first year of treatment and the duration of chronic phase of the disease was investigated. We found such correlation and also we found that the duration of the chronic phase was more significantly correlated with one year maintenance dose of busulphan. This suggests that the prognosis in CGL is more connected with the proliferation activity of leukaemic cells than with the extent of disease at the time of diagnosis. PMID- 2260411 TI - [Analysis of pregnancy, labor, child development and disease course in women with Hodgkin's disease]. AB - Twenty pregnancies were observed in 16 women with Hodgkin's disease. During 3 pregnancies cytostatic treatment was given. In 6 cases the disease was diagnosed in pregnancy and the treatment was started after labour. Eleven pregnancies were diagnosed during remission, after a mean period of 4 years (range: 6 months to 8 years) from the completion of treatment. All pregnancies had a normal course and labours were not complicated. In 2 cases of successive pregnancies disease recurrence developed. in 1 case the active disease was exacerbated. Twenty healthy babies were born, in one low birth weight was noted. The development of all children in a period of 6 years, on average, was normal. PMID- 2260412 TI - [Treatment of low-malignancy lymphomas by spleen irradiation]. AB - The spleen was irradiated in 8 patients with chronic lymphatic leukaemia using RTG radiation in doses of 225 to 800 cGy for one treatment course. The follow-up after radiotherapy lasted 12.5 months on average. In 7 cases a considerable reduction was observed in the size of the spleen, and in 6 cases the absolute leucocyte and lymphocyte counts decreased by a mean of 46% and 50% respectively. In patients in late phase of the disease the improvement was short-lasting; 5 patients died (2 from infectious complications). In patients in early phase remissions of 30 months were obtained with normalization of the proportions or T and B cells During the radiotherapy a significant rise was observed in the per cent of granulocytes and a fall of albumin level. Increased gamma-globulin and uric acid levels and decreased hemoglobin level and erythrocyte count were not significant. Variable changes were noted in the platelet count. No bleeding tendency was noted. Spleen irradiation may be used in the treatment of non Hodgkin lymphoma associated with malignant proliferation prevailing in the spleen, that is in chronic prolymphocytic leukaemia and hairy-cell leukaemia Favourable effects of spleen irradiation were observed in chronic lymphatic leukaemia and this induced us to use this method in our eight cases. PMID- 2260414 TI - [T gamma-lymphocytosis with granulocytopenia--leukemia or reaction?]. PMID- 2260413 TI - [T-cell acute lymphoblastic leukemia E(-) with antigen Ia expression]. AB - A case is presented of a rare T-phenotype acute lymphoblastic leukaemia. The blast cells were negative in the rosette test and demonstrated expression of the Ia antigen. PMID- 2260415 TI - Temporal relationships between warmth imagery and associated changes in digital pulse amplitude, skin temperature and skin temperature sensation. AB - Temporal relationships between warmth imagery and associated psychophysiological changes were studied by recording digital pulse amplitude, skin temperature, and thermal sensations in 5 subjects. After each trial the subjects were asked whether they thought they had been successful in producing the expected mental image. During the subjectively successful imagery tasks the digital pulse amplitude and the skin temperature of the hand rose significantly. The subjective onset of imagery took place after the digital pulse amplitude had started to change but before the skin temperature had begun to rise. This implies that mental imagery of skin warming as a conscious experience is not a prerequisite of somatic change. The thermal sensation (i.e. feeling of warmth) took place while the skin temperature was rising or immediately after that. This suggests that it is not caused by the mental image per se but by activation of skin temperature receptors. PMID- 2260416 TI - Ontogeny of social behavior of pups of laboratory rats genetically selected for activity level. AB - In pups of Wistar laboratory rats genetically selected for high (+A) and low (-A) locomotor activity in an open field social behavior was tested in a situation of paired interactions in a novel environment. Tests were performed on postnatal Days 16, 19, 23, and 27. They consisted of four five-minute trials with 50 min, intertrial intervals. Duration of active contacts, passive contacts, mutual grooming, following (chasing), and playful fighting was recorded. In pups of the +A line total duration of all social interactions increased between Days 16 and 23, while in the -A pairs preweaning maximum in most types of social activities was achieved already on Day 16, after this day the time spent in mutual contacts decreased. Analysis of dynamics of social behavior over trials in the -A line showed the tendency to habituate, maximum duration of paired interactions appeared in the first trial contrary to +A groups, in which duration of social contacts tended to increase with repeated trials. In both lines, duration of following responses increased from Day 16 to Day 27. In +A pairs following often led to playful fighting, while in -A pairs fighting was practically absent. The experiment demonstrated that differences between lines +A and -A appeared in those social contacts which required higher energy expenditure and which realized themselves in the larger space of the testing box. PMID- 2260417 TI - Heart rate response as indicator of mental strain: interaction of personality and situational factors. AB - Relation between mental strain defined as heart rate deviation score from person's baseline and persistence-excitation concept based on the Eysenck personality theory under various density information flow was investigated. Two groups the HPE(high EPQ-N and low EPQ-E score) and the LPE(low EPQ-N and high EPQ E score) of a nuclear power plant operators were investigated under a monotonous condition (HPE: 15 Ss; LPE:12 Ss) and under a high density information flow condition (HPE: 17Ss, LPE: 15 Ss). The data support the view that the high persistence-low inhibition individual will be more mentally strained under high density information flow and that the level of strain will decelerate more slowly in comparison to persons with low persistence-high inhibition EPQ characteristics. The low persistence-high inhibition individuals will experience higher mental strain under monotonous situations. The findings suggest that the average EPQ-E and EPQ-N score might be useful criterion for selecting persons for tasks with alternatively monotonous and cognitively demanding situations. PMID- 2260418 TI - The importance of hypothalamic centers for the pathogenesis of essential hypertension. PMID- 2260419 TI - Heart rate responses to emotionally congruent and noncongruent stimuli pairs. PMID- 2260421 TI - 32nd Annual Psychopharmacology Meeting. Jesenik Spa, Jan. 1990. Proceedings. PMID- 2260420 TI - Effect of fitness--directed physical exercise on mental state of cardiovascular patients. PMID- 2260422 TI - Outline and definitions of low flow/closed circuit anesthesia. PMID- 2260423 TI - Cardiovascular implementations of respiratory measurements. AB - Direct measurement of oxygen consumption (VO2) as an important on-line available parameter in patient monitoring has only very recently been accomplished with the development of the totally closed circuit anesthesia ventilator Physioflex. When the respiratory parameters measured with the same system and inspiratory oxygen concentration are in normal range adequate cellular oxygen supply is furthermore dependent on the following factors that influence oxygen delivery (DO2) to the tissue: the general factors, oxygen transport capacity of the blood and cardiac output and (local factors) distribution of tissue perfusion (including e.g. local occlusion, sludging, steal syndrome). In critically ill patients general impairment of oxygen delivery might occur as well as maldistribution. Studies were performed in experimental animals and patients to get some insight into the cardiovascular implementations of these respiratory measurements. Oxygen delivery has been manipulated (in pigs) by sodium nipride infusion (drop of blood pressure and cardiac output) to critical levels of oxygen supply. Endotoxin was infused with typical hemodynamic changes (first, hyperdynamic phase with increase of pulmonary artery pressure, decrease of mean arterial pressure and increase of cardiac output and, second, hypodynamic phase with low cardiac output). VO2 and oxygen delivery were controlled in a patient with a ruptured aneurysm, with impairment of oxygen transport capacity due to low hemoglobin but maintained circulating volume. PMID- 2260424 TI - Respiratory diagnostic possibilities during closed circuit anesthesia. AB - An automatic feed back controlled totally closed circuit system (Physioflex) has been developed for quantitative practice of inhalation anesthesia and ventilation. In the circuit system the gas is moved unidirectionally around by a blower at 70 l/min. In the system four membrane chambers are integrated for ventilation. Besides end-expiratory feed back control of inhalation anesthetics, and inspiratory closed loop control of oxygen, the system offers on-line registration of flow, volume and respiratory pressures as well as a capnogram and oxygen consumption. Alveolar ventilation and static compliance can easily be derived. On-line registration of oxygen consumption has proven to be of value for determination of any impairment of tissue oxygen supply when the oxygen delivery has dropped to critical values. Obstruction of the upper or lower airways are immediately detected and differentiated. Disregulations of metabolism, e.g. in malignant hyperthermia, are seen in a pre-crisis phase (increase of oxygen consumption and of CO2 production), and therapy can be started extremely early and before a disastrous condition has developed. Registration of compliance is only one of the continuously available parameters that guarantee a better and adequate control of lung function (e.g. atalectasis is early detected). The newly developed sophisticated anesthesia device enlarges tremendously the monitoring and respiratory diagnostic possibilities of artificial ventilation, gives new insights in the (patho)physiology and detects disturbances of respiratory parameters and metabolism in an early stage. PMID- 2260425 TI - The climatisation of anesthetic gases under conditions of high flow to low flow. AB - The aim of climatisation of anesthetic gases in prolonged anesthesia is to maintain tracheobronchial climate comparable to that of spontaneous nasal breathing. The humidity and temperature of inspired gases attained in the circle system at a fresh gas flow of 6.0, 3.0 and 1.5 l/min are inadequate for prolonged anesthesia. According to the results of our study with the scanning electron microscope, the minimal flow technique (0.5 l/min) leads to major improvement of heat (28 to 32 degrees C) and moisture (20 to 27 mg H2O/l) conditions of anesthetic gases in anesthesia systems. PMID- 2260426 TI - Informative imaging of multiple parameters for the practice of the anesthesiologist. AB - The development of informative design principles is necessary to permit logical, informative and understandable computer-aided imaging of the flood of measured parameters the practising anesthesiologist is currently confronted with. The computer-assisted workplace, furthermore, can use the computer to close the loop from sensor to therapy through software directed feed back control mechanisms. The general principles of information design should be based on the rule of three derived from the limited visual integration capacity of the human brain. Thus multiple parameters should be logically grouped in blocks of three strictly distinct from each other in the visual display output. Alarm signalisations have to include two senses: visual and audible and should use the large range of variability that is possible to make them distinct from each other. The operational keyboard should be logically designed with grouping in three parts: 1. a group of buttons for activation of operational screen information that appear with never more than three at the same time; 2. buttons for presetting of wanted parameter values, of alarm limits and for introduction of patient data with adjoint but strictly separated OK-mode necessity to alert that change is being made. 3. a row of buttons separated from the normal operational keyboard area for emergency changes and computer feed back mode bypass, for example. The most illogical, unoverseeable and confusing computeraided workplace can be organized to a fully assisting anesthesia workplace if proper design is applied. The use of a users' manual should be rendered unnecessary even to a computer naive user. This can be achieved through adequate informative design and operational information flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260427 TI - Does fresh gas flow rate affect monitoring requirements? AB - Opinions vary on the monitoring requirements associated with low flow to closed circuit anesthesia. Fresh gas flow rate affects variables of anesthesia ventilation such as the time constant of the breathing system, the inspired concentrations of O2, N2O and anesthetic vapor and the potential for rebreathing. Furthermore, very low flow rates challenge the performance of rotameters and vaporizers. Consequently, the safe conduct of minimal flow or closed circuit anesthesia mandates oximetry, which should be redundant; the use of anesthetic agent monitors ("anesthetico-meters") is extremely helpful, and so is capnometry. However, none of these safety monitors is beyond the scope of the "essential requirements" proposed for anesthesia workstations by international standard writing groups, such as CEN or ISO. It may hence be concluded that fresh gas flow rate does affect variables to be monitored, but it does not affect essential monitoring requirements. PMID- 2260428 TI - Mass-spectrometric evaluation of some recently introduced low flow, closed circuit systems. PMID- 2260429 TI - Clinical applications of low flow and closed circuit anesthesia. AB - Minimal Flow Anesthesia, an extreme technique of semiclosed use of rebreathing systems performed with a fresh gas flow of 0.5 l/min, can be managed with already available anesthesia machines. As a standardized fresh gas volume with fixed composition is used, due to the exponential decrease of the patient's gas uptake, the gas composition within the breathing system may change markedly during the time course of anaesthesia. Nevertheless, by this degree of fresh gas flow reduction, being very close to the patient's gas uptake, the advantages of the rebreathing technique can be achieved nearly extensively. Closed System Anesthesia, however, the anesthetic technique by which just these volumes of oxygen, nitrous oxide, and volatile anesthetics are applied, which are taken up by the patient at the particular time, can't be performed satisfactorily even if highly sophisticated equipment is used. The need for continuous adjustment of the fresh gas controls, the insufficient accuracy of the dosaging systems and the impossibility to calculate precisely the uptake figures in the individual case are essential obstacles for the routine use of this method. An account of the clinical realization of both techniques is given and the specific advantages and disadvantages are considered: although modern anesthesia machines are designed especially for the use of even lowest fresh gas flow rates, quantitative Closed System Anesthesia will not become a technique for routine clinical practice until apparatus with computer-aided closed loop feedback control of the fresh gas supply will be available. PMID- 2260430 TI - Anesthetic gas and vapor saving with minimal flow anesthesia. PMID- 2260431 TI - A proposal for a new classification of anesthetic gas flows. PMID- 2260432 TI - The efficacy and safety of nalbuphine (NUBAIN) in balanced anesthesia. A double blind comparison with fentanyl in gynecological and urological surgery. AB - In a prospective double blind study the efficacy and safety of nalbuphine as an analgesic in balanced anesthesia has been compared to fentanyl. In 63 patients, ASA class I-III, major gynecological or urological surgical procedures were performed under balanced anesthesia. Analgesia could be satisfactory maintained in all cases, but in cases of nalbuphine more hypnotics were necessary to keep the patients unconscious. The ratio of fentanyl and nalbuphine consumption was 1:200 (by weight). The nalbuphine cases can be distinguished by: more stable but higher arterial pressures and absence of arrythmia; lower incidence of nausea and vomiting in the postoperative period; less respiratory depression at the end of anesthesia, not needing antagonists, as compared to 11 patients needing antagonization in the fentanyl group; and a larger incidence of minor local allergic reactions at the injection site. Awareness was not observed in any patient of either group. Although nalbuphine has a weaker analgesic and hypnotic effect, it is perfectly possible to provide balanced anesthesia in combination with a hypnotic and a muscle relaxant. Advantages are the absence of respiratory depression as well as nausea and vomiting in the postoperative period. PMID- 2260433 TI - Effects and early perioperative diagnosis of graded reductions in regional coronary perfusion. AB - The effects of graded reductions and total occlusion of the flow in a small branch of the coronary circulation on regional myocardial function and metabolism and routinely monitored determinants of myocardial function, such as body surface electocardiogram, pressure tracings and dP/dt, are evaluated in mongrel dogs. Normal regional myocardial function and pH remain preserved until coronary blood flow is reduced to about one half its normal initial value. Then, important and dramatic changes in systolic regional myocardial function occur together with a significant decrease in regional pH. There were no significant changes in the global determinants of myocardial function. This study proves the inadequacy of the body surface electrocardiogram and the other routinely monitored hemodynamic determinants to detect limited regional ischemia. In addition, it stresses the importance to evaluate the sensitivity of new monitoring techniques in the detection of regional myocardial malfunctioning and the importance of research on the effects of anesthetic agents on regional myocardial function. PMID- 2260434 TI - Propofol handling techniques. PMID- 2260435 TI - [Anatomopathologic and clinical correlations of squamous carcinoma of the larynx and the hypopharynx]. AB - The most important problem in the diagnosis of neoplastic diseases is not only to identify its malignant nature but also the degree of aggressiveness since differences in prognosis and therapy exist in cancer as well. A short review of the literature regarding correlations between histologic degree of carcinoma and prognosis is presented. A total of 105 laryngectomy samples are presented taken by bilateral neck dissection following the principles employed for laryngeal or hypopharyngeal carcinoma. Reference is made to the following parameters: extension and site of primitive tumor; cellular (WHO), nuclear (Black) and structural (Carlon) gradings; histologic host response as judged by the presence and degree of lymphoid infiltration and fibrous stromal reactions around the primary tumor. Host response was related to structural grading. Regional nodes were studied for metastases. Nodal metastases were related to cellular, nuclear and structural grading. Clinical and statistical analysis proved that Carlon's grading, based on structural organization of the tumor, seen as a manifestation of its cellular cohesiveness, is a more discriminating system of malignancy than the others. The most organoid growth patterns (Structural grades 1 and 2) did not present any node metastases. They can be regarded as manifestations of "low grade malignancy tumors". The least organoid and non organoid growth patterns (Structural grades 3 and 4) showed higher levels of node metastases (Grade 3: 35.2%; Grade 4: 58%; p = 0.01). Necrosis was found only in Grades 3 and 4 and was associated with node metastases in 70%. Structural grading could be the guideline to better management of laryngeal carcinoma in terms of choice of surgical treatment (type of laryngectomy; neck dissection). PMID- 2260436 TI - [Latero-cervical metastasis of N0 laryngeal cancer]. AB - The authors report a pathological study of functional neck dissection performed on 145 N0 laryngeal carcinoma patients from 1982 to 1988. The incidence of occult latero-cervical metastases in N0 was evaluated in relation to site and extension of the primitive tumor. A total of 108 supraglottic, 25 glottic and 12 transglottic tumors were observed. Among the cases treated the incidence of occult metastases was 28.3% while capsular rupture accounted for 3.4%. Diagnostic error, calculated on the number of neck dissections, was 20.2%. A greater incidence of occult metastases was found in supraglottic tumors (29.6%) than in either glottic (24%) or transglottic (25%) tumors. Furthermore, incidence of occult metastases proved proportional to the extension of the primitive tumor. There was a single metastases in 35 cases while only 6 cases proved multiple. Some final considerations are given on the importance of performing precautionary functional neck dissection in N0 laryngeal cancer. PMID- 2260437 TI - [Pilot study of screening for the early diagnosis of tumors of the upper respiratory and digestive tracts in individuals at risk in the Friuli-Venezia Giulia region]. AB - A pilot study on a screening program for tumours of the upper respiratory and digestive tracts was conducted from December 1988 to May 1989 in the Friuli Venezia Giulia Region (Northern Italy), an area showing high mortality rates for cancers of these sites. Six hundred seventy-one patients at risk (i.e. habitual smokers and/or drinkers) were referred to an E.N.T. specialist by 16 general practitioners for free examination. Of these 436 (65%) actually underwent examination and, among them, 55 (12.6%) precancerosis and 8 (1.8%) epithelial tumors were detected. Although some low risk patients (mainly females) were eventually seen as well, two non-epithelial tumors being found, this pilot study would appear to have accomplished its purposes, namely to establish a closer relationship between GPs and ENT Specialists so as to discover cancerous and precancerous lesions early on and to address an educational message against smoking and heavy drinking to at risk subjects. PMID- 2260438 TI - [Distribution of laminin, type IV collagen and fibronectin in normal, dysplastic and neoplastic laryngeal tissue]. AB - The main components, both intrinsic (laminin and type IV collagen) and extrinsic (fibronectin), of the basement membrane (BM) were analyzed by immunohistochemical methods in normal, dysplastic and neoplastic laryngeal mucosa specimens. The material was obtained from 35 patients who had undergone surgery for glottic or supraglottic cancer. Fibronectin proved to be absent from normal mucosa whereas an immunopositivity was observed close to the dysplastic epithelium, especially around inflammatory cells. Positivity increased as the degree of dysplasia increased from LIN I to LIN III. A strong staining was also seen around nests of well and moderately differentiated squamous cell carcinoma. These findings are in agreement with the theories about the main sites of origin for fibronectin, both from plasma and connective tissue. Laminin and type IV collagen showed the same staining characteristics. In normal and mild dysplastic samples a regular and continuous positivity was found at the boundaries between the epithelium and the mesenchymal stroma. Focal discontinuities were present in areas of intense subepithelial inflammation only. Interruptions and reduplications were more evident in severely dysplastic epithelium. In invasive squamous cell carcinomas a strong correlation has been found between the degree of cell differentiation and the pattern of distribution of the intrinsic BM components. Immunostaining was usually evident and continuous around nests of well differentiated squamous cell carcinoma, whereas positivity progressively decreased in moderately and poorly differentiated neoplasms. Furthermore, staining for intrinsic BM components was also related to the pattern of tumor growth: continuous around the "pushing" edge of neoplastic growth and discontinuous when the neoplastic front had an "invading" appearance. These observations tend to support the theory which considers neoplastic growth a cyclic process. BM components are most likely synthesized during the phases of quiescence and reabsorbed during the phase of invasiveness, following shifts in neoplastic cell metabolism. PMID- 2260439 TI - [Quantification of communication difficulty in subjects with hearing loss: a pilot study]. AB - A brief questionnaire concerning auditory disability in every day listening was developed. The aim was to generate a simple, practical test for rehabilitational purposes. The questionnaire was administered to 255 hearing-impaired subjects coming under observation consecutively. The only requirement for participation was an expression of communicational difficulties due to adult onset of hearing loss. Some items were not applicable for all subjects. The higher scores were observed for hearing problems related to speech-in-noise. Good linear correlations were found between better-ear auditory and questionnaire score-based indexes in the 'family' and 'social' sections. PMID- 2260440 TI - [Cyclic activity of the nasal mucosa: relationship between muco-ciliary transport and local production of secretory immunoglobulin]. AB - The aim of the present work has been to study the existence, presumed on the basis of recollection, of a correlation between circadian changes in SIgA concentrations in nasal secretum and the M.C.T. rate throughout the day. In order to reconfirm previously obtained data, again in this case a fluctuation in SIgA concentration was studied, finding peak values at 4 a.m. and the lowest at 10 a.m. Circadian changes were also witnessed between M.C.T. times, thus making it possible to reveal further information regarding cyclic activity of the nasal mucosa. Comparison of these two parameters showed an inverse rate; in fact, when the SIgA concentration increases the muco-ciliary transport rate decreases and vice versa. In other words, the muco-ciliary transport time is more efficient when the production of secretory immunoglobulins by the nasal mucosa is lower, as though a temporary lack in nasal defense is made up for by simultaneous improvement of the other activity. PMID- 2260441 TI - [Post-operative recurrence of naso-sinus polyposis]. AB - Maxipolyposis, i.e. severe, diffuse nasosinusal polyposis, is generally treated with an onerous surgery. Therefore, recurrence, roughly rangling from 15% to 25%, are quite a disagreable outcome which is to be minimized. To this purpose, it may be useful to differentiate the residual from the recurrent polyposis, as is usually done in cases of cholesteatoma. Residual polyposis can be reduced by a thorough surgical resection. The authors detail their present technique, which joins microsurgery, used to perform ethmoidectomy, with endoscopic surgery, employed to manoeuvre within the sphenoid and maxillary sinus, as well as to drain the frontal sinus, i.e. to treat areas out of the direct view. Moreover, patients are warned of the need for close postoperative controls which should always be performed through telescopes in order to secure a sound inspection of the surgical cavities. Any slight, incipient recurrence should be immediately resected in the office by means of endoscopic technique. Recurrent polyposis must be treated with the drug therapies now in use, a waiting complete elucidation of the pathogenic mechanism. Association with systemic diseases, such as asthma, may contraindicate major surgery, as it increases the recurrence expectancy. Simple polypectomy often attains the same result in these cases, that is temporary ventilation of the nasal fossae. PMID- 2260442 TI - [Normal hearing, loss of hearing and general occupational disability]. AB - A real, practical definition of normal hearing is an absolutely indispensable yardstick by which to measure the degree of general occupational disability attributed to reduced auditory capacity. If progressive impairment of the organ of Corti, due to age and non-occupational noise factors is also taken into account, a practical borderline between normal and reduced hearing can be defined as a mean bilateral threshold level for air conduction higher than 25 dB for the usual conversational frequencies, as per D.P.R. 1124/1965 and in accordance with ISO R/389/1964 and ANSI/1969. Suggestions are also put forward for the definition of general occupational disability. PMID- 2260443 TI - [Embryonal rhabdomyosarcoma of the middle ear: description of a case with long term survival]. AB - A case is described of embryonal rhabdomyosarcoma (E.R.) of the middle ear in a 4 year-old child; survival has been over 9 years. R.E. is the most common malignant tumor of the auricular region in children and is most often fatal due to locoregional extensions or secondary metastases carried through the bloodstream and lymphatic systems. The basis for treatment is a multidisciplinary approach to the disease: surgery with as broad an exeresis as possible; radiotherapy with tumor-killing doses of 5,500/6,000 rads; and polychemotherapy (Vincristina, Endoxan, Methotrexate). Such "aggressive" treatment often results in a high rate of morbidity with complications involving the blood, bones, eyes and meninx often requiring temporary suspension of treatment and prolonged hospitalization. PMID- 2260445 TI - 9th International Symposium on growth and growth disorders. Proceedings of a meeting held in Edinburgh, UK, 6-7 April 1990. PMID- 2260444 TI - [A case of rhabdomyosarcoma of the parotid region]. AB - The present paper reports a case of rhabdomyosarcoma in a 4-year-old patient, the rapidity with which it spread and the intensity of its extension bringing the case under observation. It is, in fact, a case of embryonal rhabdomyosarcoma localized in the right parotid area with an extension to the temporal fossa, to the epi-oro-hypopharynx as far as the lateral vertebral region with C5-C6 involvement and penetrating the medium cranialis fossa. Initially the child showed signs of tissue growth at the right parotid site, originating without symptoms and rapidly increasing in volume. As exploratory surgery revealed that it would be impossible to achieve radical removal of the growth, the authors opted for radio-chemotherapy treatment. This type of approach, however, gives short lived results, in this case evidenced by recurrences within six months and leading to the patient's death after just eight months. It is important to stress the rapid evolution of this neoplasm, its tendency to recur and metastasize as well as its poor prognosis in general. PMID- 2260446 TI - New insights from a large international collaborative growth study. Introduction. PMID- 2260447 TI - The Kabi International Growth Study: concept and organization. PMID- 2260448 TI - Who is treated with growth hormone today? The Executive Scientific Committee of the Kabi International Growth Study. AB - The present demographic data from the Kabi International Growth Study (KIGS) database are summarized. Of the 2580 patients included, 85% have growth hormone deficiency (GHD) and 15% have other causes of growth failure. Idiopathic GHD is present in 78.5% of the patients, the remaining 21.5% have organic GHD. Isolated GHD is common in idiopathic GHD whereas multiple pituitary hormone deficiencies occur in at least 50% of the organic GHD patients. A preponderance of boys is observed in most groups of patients. Median chronological age (CA) at start of treatment is 10 years and median duration of therapy is 2.3 years. However, a wide range is observed. In most cases growth retardation is severe. In most patients with GHD height SDS for chronological age at start of therapy is at or below -3. The median difference between idiopathic and organic GHD is 1 SDS. Most patients have 6 or 7 injections of growth hormone (GH) per week. The median total weekly dose is approximately 0.5 IU/kg/week, but it is lower in older patients. It is concluded that steadily increasing numbers of patients with idiopathic and organic GHD are being treated with human GH (hGH). In addition, many patients with other growth disorders not necessarily associated with GHD receive hGH therapy. Chronological age at start of treatment still appears to be (too) high in most patients and growth retardation severe. The frequency of hGH injections has been increased to nearly daily administration. However, the total weekly dose appears to be low, especially in the older patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260449 TI - Birth data for patients who later develop growth hormone deficiency: preliminary analysis of a national register. The Executive Scientific Committee of the Kabi International Growth Study and the Swedish Paediatric Study Group for Growth Hormone Treatment. AB - This study analyses gestational age, mode of delivery and size at birth in children who later developed idiopathic or organic growth hormone deficiency (GHD). A data register of children on growth hormone (GH) treatment in Sweden was compared with the Swedish Medical Birth Register during a 14-year period (1973 1986) comprising 1.4 million newborn children. Size at birth was evaluated using a new Swedish reference standard based on data from around 500,000 newborn children. It was found that the children who later develop idiopathic GHD (IGHD) were born with a normal distribution of gestational age. They were more often born with breech delivery (7.1% versus 2.8%) or caesarean section (16.6% versus 10.4%) compared with normal children. The children's condition at birth was poorer than normal, as shown by the frequency of Apgar scores below 7 at 5 minutes (5.2% versus 1.2%). Finally, it was found that children who later develop IGHD (n = 220) had a median birth length of 0.87 SDS below the mean and a median birth weight of 0.60 SDS below the mean of the standard. In contrast, both the birth length and weight of the children who later develop organic GHD (OGHD) (n = 92) did not differ from that of the reference. PMID- 2260450 TI - Growth response in prepubertal children with idiopathic growth hormone deficiency during the first year of treatment with human growth hormone. Analysis of the Kabi International Growth Study. AB - In order that children with growth hormone deficiency (GHD) reach the goal of normal adult stature, treatment modalities need to be optimized. From the large database of patients enrolled in the Kabi International Growth Study (KIGS), 257 prepubertal patients with idiopathic GHD undergoing their first year of growth hormone (GH) substitution therapy were selected. A multiple regression analysis was performed to determine both auxiological factors characterizing the patients and the factors related to the chosen treatment modalities which are of significance for the observed magnitude of the growth response. Due to the structure of the data, pretreatment height velocity and bone age-derived auxiological data were not considered. It was observed that the magnitude of the growth response was inversely correlated with chronological age and relative height (HT SDS) at the start of GH treatment but was positively correlated with mid-parental height. The growth response was also positively correlated with the GH dose (IU/kg/week) and the frequency of GH injections per week. A regression equation using these five parameters was derived, allowing the growth response of these patients to be predicted. The extension of this analytical approach in the future will allow the treatment of patients with GHD to be tailored to individual requirements. PMID- 2260451 TI - Growth response in the first year of growth hormone treatment in prepubertal children with organic growth hormone deficiency: a comparison with idiopathic growth hormone deficiency. The Executive Scientific Committee of the Kabi International Growth Study. AB - Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted. PMID- 2260452 TI - Aetiology and pathogenesis of growth hormone deficiency. PMID- 2260453 TI - Genotropin 16 IU KabiVial is more convenient than conventional administration systems for children on growth hormone therapy. AB - The use of a new device for reconstitution and storage of growth hormone (GH), Genotropin KabiVial, was studied in 20 children, aged 9-17 years, who had been receiving GH therapy using conventional administration systems. After 2 weeks of treatment, the convenience of the device and the patients' tolerance of it were assessed by the patients/families through a questionnaire. They were asked to compare the new device with the conventional method (standard vials and syringes). Most of the patients found the new device superior to the conventional method; they found that it was easier to reconstitute the GH and considered the multi-dose system and the smaller injection volume to be advantageous. Ninety per cent of the patients (p less than 0.001) expressed a preference for Genotropin 16 IU KabiVial for their future therapy. PMID- 2260454 TI - Treatment of growth hormone deficient patients with recombinant somatropin for 1 year: results of a Chinese multicentre trial. AB - Fifty-nine patients with idiopathic growth hormone deficiency were included in a Chinese multicentre trial of recombinant somatropin, 0.5-0.7 IU/kg/week s.c. given in six or seven divided doses. The height velocity increased from 2.8 +/- 1.0 cm/year to 13.1 +/- 2.5 cm/year during 1 year of treatment, and typical catch up growth was observed. The increase in height SDS for chronological age was significant, but the increase in height SDS for bone age was not statistically significant. No adverse reactions to the treatment were recorded. Recombinant somatropin was shown to be very effective and safe during the first year of therapy in patients with growth hormone deficiency. PMID- 2260455 TI - Growth hormone and insulin-like growth factor I in chronic renal failure- pathophysiology and rationale for growth hormone treatment. PMID- 2260456 TI - Recombinant human growth hormone treatment in short children with chronic renal disease, before transplantation or with functioning renal transplants: an interim report on five European studies. AB - Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection. PMID- 2260457 TI - Recombinant human growth hormone treatment of children with chronic renal failure: update 1990. AB - Nine children with growth retardation due to chronic renal failure were treated with recombinant human growth hormone (rhGH) for 12-36 months. Results demonstrated a significant increase in height velocity at each 12-month interval compared with that achieved during the year prior to treatment. However, the increase in bone age was no greater than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uraemia following treatment. Currently, 6 of 7 patients who have been treated for more than 24 months have achieved sufficient acceleration in height velocity to attain an SDS of less than -2.00 and are above the 5th centile for chronological age on the growth curve. These updated data indicate that rhGH treatment of growth retarded children with chronic renal failure continues to result in accelerated height velocity during the second and third year of treatment, and demonstrate the potential for such children to achieve normal stature (+/- 2 SD) for chronological age despite the continued presence of chronic renal failure. PMID- 2260458 TI - Pride and prejudice--stature in perspective. PMID- 2260459 TI - Assay of growth hormone levels in human plasma using commercial kits: analysis of some factors influencing the results. AB - The reliability of growth hormone (GH) assays, performed in 39 different laboratories, using five different immunoassay kits was evaluated. It was found that the variability in GH levels measured by different commercial assay kits may be due to human factors, as well as differences between the kits. The influence of the variation in amount of circulating GH, during provocative testing and spontaneous secretory episodes, on the results of GH assay was also evaluated. It was found that large molecular weight forms of GH may be underestimated by some assay kits. PMID- 2260460 TI - Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children. AB - Forty-eight children, referred for evaluation of short stature, underwent 24-hour spontaneous growth hormone (GH) secretion studies. The GH level in pooled sera was assessed for each child, using up to 11 commercial immunoassays. In a group of 15 children, the mean GH values obtained by nine of the assays were compared with the mean value given by a polyclonal radioimmunoassay (RIA) from Sorin: four gave higher results (p less than 0.0001), three gave comparable results and two gave lower results (p less than 0.001). The assay yielding the highest results (Nichols: 5.9 +/- 2.3 ng/ml, mean +/- SD) gave values that were approximately triple those obtained by the assay yielding the lowest results (Hybritech: 1.8 +/ 0.8 ng/ml; p less than 0.0001); both of these are monoclonal immunoradiometric assays (IRMAs). The GH concentrations measured in 24-hour pools from 32 children using a monoclonal IRMA from Biomerieux were similar to those obtained using a polyclonal RIA from Farmos (2.8 +/- 1.1 ng/ml and 2.9 +/- 1.4 ng/ml, respectively) but significantly lower than those measured by another polyclonal RIA from Sorin (3.5 +/- 1.5 ng/ml). Two polyclonal assays (Biomerieux and Sorin) were then used to measure the GH levels in all of the 30-minute samples and in the day, night and 24-hour pools from the secretion studies of 22 children. The ratio of the results of the two assays remained fairly constant for a given child (although the GH levels in different 30-minute samples differed considerably). However, the ratios between different children showed quite wide variation (from 2.03 to 1.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260461 TI - Growth hormone binding proteins and various forms of growth hormone: implications for measurements. AB - GH measurements are complicated by numerous physiologically occurring GH forms, by the lack of availability of completely specific reagents for the various GH isoforms, and by interference of the circulating BP in some assays. The discrepancies between assay results are partly due to these factors, with monoclonal immunoassays or RRAs being more affected than polyclonal immunoassays. PMID- 2260462 TI - Receptor assays for growth hormone. PMID- 2260463 TI - Separation and identification of growth hormone variants with high performance liquid chromatography techniques. AB - Liquid chromatography techniques were used to separate and identify human growth hormone (hGH) variants. N-terminal modified forms, such as des-Phe (2-191) and methionyl-hGH (met-1-191), were separated from recombinant human growth hormone (rhGH (1-191] by hydrophobic interaction chromatography (HIC). A proteolytically cleaved ('clip') form of rhGH which has a break in the polypeptide chain between Thr(142) and Tyr(143), also proved to be separable from rhGH by HIC. In addition, a mutated form of rhGH with only two amino acid substitutions, Glu(65) to Val(65) and Glu(66) to Lys(66), on a random coil domain of the molecule, was separated from rhGH by HIC, indicating that these substitutions altered the hydrophobicity of the molecule. Treatment of rhGH with hydrogen peroxide led to sulphoxide formation in two methionine residues Met(14) and Met(125); it was not possible to oxidize Met(170). The oxidized forms of rhGH were readily separated from rhGH(1 191) by reversed-phase chromatography. Analyses of rhGH batches showed very low levels (less than 0.3%) of oxidized rhGH, indicating that rhGH is highly resistant to oxidative reactions. Deamidations were induced in rhGH by heat treatment. The primary deamidation site was found to be Asn(149). Monodesamido rhGH and didesamido rhGH were efficiently separated from rhGH(1-191) by anion exchange chromatography. PMID- 2260464 TI - Continuous ambulatory peritoneal dialysis for children with end stage renal disease. AB - From June 1986 to October 1989, ten children suffering from end stage renal disease (ESRD) were treated with continuous ambulatory peritoneal dialysis (CAPD). Their ages ranged from 4 to 16 years; 3 were boys and 7 were girls. IgM mesangial nephropathy (IgMN) (three cases) were the most common causes of renal failure in the patients. All patients were trained in the hospital. After CAPD treatment, serum BUN and creatinine dropped significantly. Serum levels of potassium, phosphorus, and alkaline phosphatase dropped and serum sodium and calcium rose significantly after treatment. Improvement of anemic state and control of hypertension were also noted. Hypercholesterolemia and hypertriglyceridemia developed after CAPD treatment. Despite protein loss through the peritoneal cavity, there was no evidence of protein malnutrition. Total serum protein and albumin increased significantly after treatment. The most common complication was peritonitis. Three of these 10 patients developed an episode of peritonitis, or an incidence of 1 episode per 17.2 patient months. To the present, seven patients are still doing well on CAPD. Three patients have received renal transplantation. The majority of the patients experienced an increased sense of well-being, easier diet and fluid management, freedom for travel and daily activities. Physical development also improved, with body length and body weight gaining steadily. It can be concluded that CAPD is a good modality of long-term therapy for ESRD children. PMID- 2260465 TI - Periventricular leukomalacia in infancy: ultrasonic diagnosis and neurological outcome. AB - During the more than five years from January 1984 to June 1989, twenty-four patients with definite or probable cystic periventricular leukomalacia (PVL) were diagnosed by cranial ultrasonography at Mackay Memorial Hospital. The 24 patients were divided into two groups. Group A comprise two boys and four girls who received longitudinal sonographic follow-ups for leukomalacia. Of these six patients, five were premature and all suffered from severe perinatal insults. In each case, sequences of developmental cystic PVL were observed by serially scanning the brain. High echogenicity was discovered during the initial stages (2 to 7 days) in the periventricular area, and cystic formations were observed between the age of 18 and 60 days. Clinically, only one patient developed normally; four had severe motor dysfunction and poor motor development; and one was lost during follow-up, Group B was composed of 18 patients who visited the out-patient clinic for psychomotor retardation evaluation, and were found through ultrasound to have or possibly have cystic PVL formations at various stages. The clinical work-up revealed that 12 had spastic quadriplegia; 2 had hemiplegia; 3 had spastic displegia; and 1 case had hypotonic cerebral palsy. In infants, PVL is considered to be a much more reliable and important prognostic predictor than intraventricular hemorrhage. Consequently, it is crucial that physicians should screen patients at high risk for PVL, especially those with perinatal insults. PMID- 2260466 TI - [Measurements of anterior fontanels in Chinese]. AB - Assessment of the size of the anterior fontanel is used as an index of cranial development from birth to the second year of life. From January to May, 1988, measurements of anterior fontanel size were collected for all available newborns and infants from the nursery and well-baby clinics. The size of anterior fontanel was measured as the average value of the length (anterior-posterior dimension) and the width (transverse dimension), as proposed by Popich in 1972. Any fontanel too small to be measured was judged to be closed. Totally 704 subjects, divided into 10 groups by age (3 days, 1, 2, 4, 6, 9, 12, 15, 18, and 24 months) were measured. Results showed that the mean size of anterior fontanel in these 10 groups was 26.7 mm, 25.8 mm, 24.9 mm, 25.7 mm, 20.2 mm, 14.9 mm, 11.5 mm, 10.2 mm, 13.0 mm, and 12.1 mm, respectively. Results also showed a variation of fontanel size in all groups. There was a tendency toward decrease in fontanel size after six months of age. There were no significant differences in size and age of closure of the anterior fontanel between two sexes. Closure of the fontanel was first noted in about 5% of the babies 6 months after term, but in about 8% of the babies at 24 months of age, the fontanel had not closed. The median age of fontanel closure was 14.5 months in males and 14.3 months in females. PMID- 2260467 TI - Fetal alcohol syndrome: report of one case. AB - A male premature baby, whose mother was an alcoholic, was diagnosed as a case of fetal alcohol syndrome according to the following: (1) early-onset intrauterine growth retardation and persistent postnatal growth failure; (2) psychomotor retardation; (3) craniofacial dysmorphism; (4) tetralogy of Fallot; and (5) radioulnar synostosis. The literatures on the clinical manifestation, pathogenesis, and outcome of fetal alcohol syndrome are reviewed. PMID- 2260468 TI - Immature mediastinal teratoma in early infancy: report of one case. AB - Immature mediastinal teratomas are rare, found in only 1% of all mediastinal teratomas; those occurring in the neonatal period are even more rare. A male baby suffering from tachypnea, weak crying and hoarseness since birth was noted, from a chest radiograph, to have a superior mediastinal mass. This mass enlarged progressively to an extent that the airway was threatened by one month of age. After resuscitation, intubation and mechanical ventilation, the infant became respirator-dependent. Chest computed tomography and ultrasonography revealed a heterogeneous cystic tissue mass containing focal calcifications. A well encapsulated tumor, measuring 6 x 4 x 4 cm in size, located anterior to the thymus, was successfully removed at 58 days of age. The pathology showed an immature teratoma. After operation, respiratory distress dramatically improved. However, a superior mediastinal mass reappeared on a chest roentgenogram four months later. After a short course of chemotherapy, the infant received another operation to excise a mass composed of hypertrophic thymic tissue and a small nodular mature teratoma. The patient has remained well for more than nine months now. PMID- 2260469 TI - [Neonatal group B streptococcal pneumonia and right-sided diaphragmatic hernia: report of one case]. AB - The symptoms of right-sided diaphragmatic hernia (RDH) rarely occur in the newborn period. The present report described a two-day-old neonate who presented with symptoms of respiratory distress and sepsis. Early onset group B beta hemolytic streptococcal (GBBS) infection was diagnosed and RDH was found subsequently. A defect with smooth margin, sized 3 x 5 cm, located in posterior lateral aspect of right diaphragm was observed during operation. After having been given antibiotics and surgical treatment, the infant recovered and was discharged in good condition. He has normal development at the age of one year. Possible pathogenesis is discussed in this report. PMID- 2260470 TI - [Hemolytic disease of the newborn caused by maternal irregular antibody anti-E: report of one case]. AB - A 3390 gm male baby was born smoothly at 41 weeks' gestation to a 35-year-old, gravida 3, para 3, mother by spontaneous vaginal delivery at this hospital. The mother denied ever having received a blood transfusion. Her first two uneventful pregnancies had resulted in two healthy fullterm infants. Physical examination of the baby showed normal, until 15 hours of age, when apparent jaundice with serum total bilirubin concentration up to 21 mg/dl was noted. The blood types of both baby and mother were group A, Rh(D) positive. Compatibility testing for exchange blood transfusion with group A whole blood showed positive reaction due to the presence of an irregular antibody. Two exchange blood transfusions were performed in the same day with compatible blood. Thereafter, the patient's condition was much improved, he was discharged one week later. The irregular antibody--anti-E was identified in both baby and mother. The maternal RBC phenotyping was CCDee (R1R1), and the baby, CcDEe (R1R2). PMID- 2260471 TI - [Congenital hypothyroidism missed on newborn screening: report of two cases]. AB - Two male term babies were born at Mackay Memorial Hospital; both were born without incident. Newborn screenings (including phenylketonuria, homocystinuria, galactosemia, congenital hypothyroidism and G-6-PD deficiency) were performed at the age of three days and judged to be normal. In the later neonatal period, case 1 gradually developed prolonged jaundice, poor feeding and poor weight gain. The rechecked thyroid stimulating hormone (TSH) level was 276.3 mU/l. Case 2 was admitted with seizures; the TSH level, rechecked by chance, showing 11.6 mU/l. Under the suspicion of congenital hypothyroidism, serum confirmation tests were performed and showed TSH 393.6 mU/l, 37.09 mU/l and T4 2.87 micrograms/dl, 4.59 micrograms/dl, respectively. The diagnosis was, thus, congenital hypothyroidism with delayed rise in TSH level. The conclusion is that, regardless of the result of newborn screening, a serum confirmation test (T4 & TSH level) should be done in any infant who is suspected to have congenital hypothyroidism. PMID- 2260472 TI - Microvesicular fatty liver in rats with resembling Reye's syndrome induced by 4 pentenoic acid. AB - To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90 min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA-treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats. PMID- 2260473 TI - The effects of hyperfiltration on serum sickness glomerulonephritis in rats. AB - The effects of hyperfiltration induced due to unilateral nephrectomy on immunologically induced glomerular injuries were studied. Glomerulonephritis was induced in rats by sensitizing them with egg albumin as an antigen. Unilateral nephrectomy did not affect the removal rate of the antigen from the glomeruli in the rats, but accelerated the rate of the glomerular injuries after cessation of the immunologically induced glomerular inflammation. The histopathological features were characterized by sclero-adhesive lesions with aneurysmal dilatation and hyalinosis of the glomerular capillaries. The parietal epithelial cells extended from the Bowman's capsule with matrices to cover the denuded basement membrane and formed adhesions. The neighboring capillaries collapsed, and the sclero-adhesive lesions progressed. These findings indicate that hyperfiltration at the capillary level did not accelerate the recovery from glomerulonephritis, but induced glomerular sclerosis with adhesions and deteriorated the trivial glomerular injuries to produce similar focal segmental lesions. PMID- 2260474 TI - A statistical analysis of lung cancer registered in the Annual of Pathological Autopsy Cases in Japan between 1958 and 1987, with special reference to the characteristics of lung cancer in Japan. AB - Autopsy cases of lung cancer, 41,988 in males and 13,818 in females, consecutively registered between 1958 and 1987, were analysed statistically and compared with other case materials and mortality statistics. Cases of malignant tumor showed a gradual increase, and now comprise 60% of the total male and 55% of the total female autopsy cases. The percentage of lung cancer cases among the total autopsy cases was 9% for males and 5% for females. The percentage of lung cancer cases among total cases of malignant tumor was about 17% for males and 9% for females. Among fatal malignant tumors, gastric cancer and lung cancer showed the highest frequency. The relative incidence of gastric cancer was seen to decrease, whereas that of lung cancer increased. Of the histological types of lung cancer in both sexes, adenocarcinoma was the most frequent, followed by squamous cell carcinoma. During the period studied the peak age of patients with lung cancer shifted from the seventh to eighth decade, and a significant elevation of mean age was demonstrated for all of the major histological types in both sexes. The male:female ratio for all lung cancer cases was 3.0, which was much lower than those for the United States and Europe, but very similar to the ratios of mortality statistics in Japan and other Asian countries. As a result of a previous autopsy study at the University of Tokyo, it was also confirmed that the male:female ratio relative to age in each country reflects very well the histological distribution. PMID- 2260475 TI - Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence. AB - We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma. PMID- 2260476 TI - Sequential malignant transformation of cardiac myxoma. AB - We describe a case of cardiac myxoma in a 44-year-old Japanese man, who died after developing metastases in the skin, brain and muscle. A satellite tumor which was attached to the wall of the abdominal aorta induced marked hypertension due to obstruction of the renal arteries. Although the primary heart tumor had typical histological features of benign cardiac myxoma, the recurrent heart tumor, which was partly resected three months before the patient's death, showed apparently malignant characteristics resembling malignant fibrous histiocytoma (MFH). Since the histological features of the initial and recurrent tumors were different, the grade of malignancy was investigated using the cellularity of the tumor as an arbitrary criterion. A gradual but significant increase in the cellularity was observed over the course of five years. Immunohistochemically, tumor cells in the muscle metastasis contained vimentin and factor VIII-related antigen, and multinucleated giant cells in the recurrent heart tumor contained desmin, which is rarely detectable in MFH. Therefore, we considered that the present case represented malignant transformation of benign cardiac myxoma. PMID- 2260477 TI - Postmortem diagnosis of acute megakaryocytic leukemia. Usefulness of immunohistochemistry and tissue hemogram. AB - An autopsy case of acute megakaryocytic leukemia (AMKL) is presented. The bone marrow was hypercellular with proliferation of three lineages, especially megakaryocytes. Immunohistochemical examination revealed many platelet glycoprotein IIb/IIIa (GP IIb/IIIa)-positive blast cells in bone marrow. The proportion of the blasts was 26.4% by tissue hemogram. GP IIb/IIIa-positive blasts and megakaryoblasts were deposited massively in lymph nodes. Immunohistochemistry against GP IIb/IIIa and tissue hemograms by paraffin section are needed to diagnose AMKL by postmortem examination, since the identification of ultrastructural platelet peroxidase in autopsy materials is difficult. PMID- 2260478 TI - A case of liver cirrhosis with a hyperplastic nodular lesion. AB - A hyperplastic nodular lesion resembling focal nodular hyperplasia (FNH) was found in the cirrhotic liver of a 50-year-old male patient. A nodule was detected by ultrasonography and hepatic angiography conducted as part of a routine follow up study for chronic liver disease, and was excised under a diagnosis of suspected hepatocellular carcinoma. Grossly, central stellate scar-like septa subdividing the nodule ware noted. These fibrous septa contained many small arteries and veins, as well as bile ducts. The parenchyma of the nodule also contained many small arteries. Although these findings were similar to those seen in typical FNH, the present lesion was different in that it was encapsulated, occurred against a background of liver cirrhosis, lacked hepatocyte hyperplasia and showed hemosiderin deposition. PMID- 2260479 TI - Relationship of psychotic symptoms to haloperidol-stimulated prolactin release. AB - Prolactin (PRL) response to a single dose of intravenous haloperidol (0.5 mg) was measured as a marker of tuberoinfundibular dopamine (TIDA) activity in 24 neuroleptic-free, male, psychotic patients. The PRL responses were then correlated with psychotic symptoms measured with Andreasen's Scales for the Assessment of Positive and Negative Symptoms (SAPS, SANS). Correlation analyses revealed a significant inverse relationship between PRL response and the severity of delusional symptoms. There was no significant correlation between the symptoms of hallucinations, formal thought disorder, or global negative symptoms and PRL response to haloperidol, nor were there any significant correlations between basal PRL and symptom severity. These results suggest that among the positive and negative symptoms associated with psychoses, only delusions may be associated with TIDA overactivity. PMID- 2260480 TI - P300 and smooth eye pursuit: concordance of abnormalities and relation to clinical features in DSM-III schizophrenia. AB - Twenty-five DSM-III-diagnosed schizophrenics and 37 normal and age-matched controls were examined using an oddball paradigm for the generation of P300 and smooth eye-pursuit tasks. Results were compared between groups and related to clinical characteristics, including a family history of psychiatric illness. Group differences were found for P300 amplitudes, latencies and eye-tracking. A family history of psychiatric illness was associated with normal eye-tracking in patients. Small P300 amplitudes alone and in combination with long P300 latencies were associated with a family history in controls. PMID- 2260481 TI - Coping styles to basic disorders among schizophrenics. AB - Coping efforts to subjectively experienced basic disorders were investigated by self-report in 60 chronic schizophrenics in Japan, and the relationships to clinical and demographic variables, intelligence, personality, and attitude toward their illness were analyzed. Self-reports on coping efforts were obtained for more than half of all subjectively experienced basic disorders, and the predominant technique was reported to be the approach oriented towards problem solving. Within each coping style, the behavioral change, divertive problem solving approach correlated negatively with hospitalization and symptoms, and the struggle, problem-solving efforts without any effective results correlated positively with symptoms. Suggestions regarding integration of these self-efforts into psychosocial treatment of schizophrenia are discussed. PMID- 2260482 TI - Risk factors of alcoholism in Taiwan Chinese: an epidemiological approach. AB - This study investigated the risk factors of alcohol abuse and alcohol dependence, as defined by DSM-III criteria, in 11,004 Chinese subjects in the Taiwan community. Risk factors were analyzed using chi-square and multivariate logistic regression statistics. The logistic regression shows that the risk factors of alcohol dependence include male, having had childhood or adulthood behavior problems; of alcohol abuse include male, having had childhood or adulthood behavior problems, non-metropolitan community, age cohort, job-holder. The etiological models proposed are biological for Chinese alcohol dependence and interactional for Chinese alcohol abuse. PMID- 2260483 TI - Prolactin responses in dexamethasone suppression test in patients with anorexia nervosa. AB - In anorexia nervosa (AN), abnormalities are present in the hypothalamic-pituitary adrenal axis, but the prolactin (PRL) response to dexamethasone suppression test (DST) has not yet been studied. In order to study the interrelationships between the various endocrine abnormalities, we investigated the responses of PRL and cortisol to DST (1 mg of dexamethasone at 2300) in AN patients. The subjects were 12 female inpatients with AN and 8 age- and sex-matched healthy controls. The percentage suppression and absolute change in PRL levels before and after dexamethasone administration were significantly different in the 2 groups. In the control group PRL levels suppressed to 36.5 +/- 3.7% of basal, while AN levels declined to 79.4 +/- 8.9% of basal. When the percentage suppression of PRL was compared between patients with and without cortisol suppression, the mean PRL level was 68.9 +/- 7.8% of the basal level for the cortisol-suppressed patients and 100.4 +/- 19.1% for the nonsuppressed patients. Hence in both groups, the percentage PRL suppression was significantly reduced compared with the control group, and indeed nonexistent in cortisol-nonsuppressed patients. The finding that there was less PRL suppression in the cortisol-suppressed patients than in the controls suggests that, in AN, there may be an abnormality in PRL secretion not related to the hypothalamic-pituitary-adrenal axis. Further work is needed to distinguish between the PRL response to stress and potential hypothalamic abnormality. PMID- 2260484 TI - Internal consistency and factor structure of the Chinese Health Questionnaire. AB - The internal consistency and factor structure of the Chinese Health Questionnaire (CHQ) were investigated in 2 samples in Taiwan, one from 3 communities (n = 1023) and the other from consecutive attenders for health screening in a general hospital (n = 386). Cronbach's alpha coefficients were calculated to be 0.84 and 0.83 for the 12-item and 0.90 and 0.92 for the 30-item CHQ version. Four factors similarly extracted for the CHQ-30 in both samples include somatic symptoms, anxiety and worrying, social dysfunction, and depression and poor family relationship. The implications of these findings were discussed from a cross cultural perspective. PMID- 2260485 TI - Celibacy and fertility rates in patients with major affective disorders: the relevance of delusional symptoms and suicidal behaviour. AB - The celibacy and fertility rates of 186 patients with major affective disorders were analysed as a function of the presence or absence of histories of mood congruent delusions or suicidal behaviour in the depressive phases of the disease. Both delusional and suicidal histories were irrelevant to celibacy rates. On the contrary, delusional depressives had a reduced incidence of cases with 2 or more children and suicide attempters had both a lower frequency of high fertility cases and a smaller mean number of children than nonattempters. The differences were apparently not attributable to the length of the fertile period of life spent in illness. PMID- 2260486 TI - The late effects of Nazi persecution among elderly Holocaust survivors. AB - Eighty-six survivors of the Holocaust from a nonclinical population were interviewed to examine the recent mental state, coping and adjustment of elderly Holocaust survivors. Most of the interviewees suffered after the war and are still suffering from the results of persecution. Death camp survivors suffer more than survivors who were subjected to other forms of Nazi persecution. Despite the mental suffering, Holocaust survivors succeeded to cope and to adjust. They are successful at work and in society. They managed to raise warm families. They behaved and still behave as if fulfilling a testament to those who perished. PMID- 2260487 TI - Charles Bonnet syndrome: a description of two cases. PMID- 2260488 TI - Disease consciousness and coping strategies of patients with schizophrenic psychosis. AB - In 50 schizophrenic patients, semistructured interviews were carried out concerning disease consciousness, occupation with the disease and behaviour and coping in case of psychotic experiences; 72% of the patients occupied themselves with their disease. In 84% a disease consciousness was present; 38% gave a multifactorial explanation for their psychosis. In 94% the occasional appearance of psychotic experiences was acknowledged. In 86% specific changes of the individual behaviour for coping with these experiences were described. These changes included withdrawal, increasing of interpersonal contact, cognitive control, symptomatic behaviour and adjustment of the neuroleptic medication. The study shows that schizophrenic patients are not passive victims of their disease. In the majority of cases a disease consciousness is present. The patients try to cope with their psychotic experiences in individually different ways. It is assumed that a better knowledge of these strategies might enable the clinician to use these phenomena as an adjunct to pharmacotherapy. PMID- 2260489 TI - A longitudinal study of cerebrospinal fluid beta-endorphin-like immunoreactivity in delirium: changes at the acute stage and at one-year follow-up. AB - Cerebrospinal fluid beta-endorphin-like immunoreactivity (CSF BLI) was determined on 3 occasions for elderly delirious patients and the BLI levels were compared with age-equivalent controls. Delirious patients showed a significant reduction in the BLI values in the first sample and a declining trend was seen in the follow-up. The results suggest a role for beta-endorphinergic dysfunction in the genesis of some symptoms of delirium, and this dysfunction may be a common phenomenon in various forms of delirium and dementia. PMID- 2260490 TI - Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease. AB - Vitamin B12 levels in the serum and the cerebrospinal fluid (CSF) were compared between patients with Alzheimer's disease (AD) and senile dementia of Alzheimer's type (SDAT) (AD group) and patients with multi-infarct dementia (MID group). The B12 levels in the serum and the CSF were 742 +/- 359 pg/ml and 28 +/- 7 pg/ml (mean +/- SD), respectively, in the AD group, and 962 +/- 254 pg/ml and 50 +/- 26 pg/ml, respectively, in the MID group. CSF B12 levels were significantly lower in the AD group than in the MID group, whereas the serum levels were not different. At the same time, the serum levels of almost all patients were within the normal range, whereas the CSF levels were 25 pg/ml or lower in 10 of 12 AD patients. Therefore, this low level in the CSF is considered to be a characteristic finding in the AD group. PMID- 2260491 TI - A stochastic model for inter-keypress times in a typing task. AB - A mathematical model for the inter-keypress times (IKT) in a typing task is proposed. The model, which includes a diffusion process terminated by a single response threshold, was evaluated using data obtained from typists. The differences in performance for successive cross-hand and within-hand keypresses were examined using IKT distributions and hazard functions, and it was shown that the empirical hazard functions could be fit by the theoretical hazard function derived from the convolution of normal and inverse Gaussian random variables. Some possible applications of the model for the evaluation of fatigue and strategic effects in typing are suggested. PMID- 2260492 TI - Auditory accessory effects on visual processing. AB - A series of experiments on intersensory facilitation demonstrates that non informative sound of low to moderate intensity (30/80 dB) facilitates the reaction to a visual stimulus. By manipulating the preprocessing and perceptual stages of the visual signals, it appears that auditory intensity reduces choice reaction time independently from the positive influence of the intensity and duration of the visual imperative signal, but interacts with the effect of stimulus degradation. Degraded stimuli take more profit of the sound than intact stimuli. Besides a short-term activation effect, originated by accessories of the auditory modality, on the motor adjustment stage (cf. Sanders 1983), the results suggest that the accessory influences the stage of feature extraction. PMID- 2260493 TI - Interference with visual short-term memory. AB - Working memory (Baddeley and Hitch 1974) incorporates the notion of a visuo spatial sketch pad; a mechanism thought to be specialized for short-term storage of visuo-spatial material. However, the nature and characteristics of this hypothesized mechanism are as yet unclear. Two experiments are reported which examined selective interference in short-term visual memory. Experiment 1 contrasted recognition memory span for visual matrix patterns with that for visually presented letter sequences. These two span tasks were combined with concurrent arithmetic or a concurrent task which involved manipulation of visuo spatial material. Results suggested that although there was a small, significant disruption by concurrent arithmetic of span for the matrix patterns, there was a substantially larger disruption of the letter span task. The converse was true for the secondary visuo-spatial task. Experiment 2 combined the span tasks with two established tasks developed by Brooks (1967). Span for matrix patterns was disrupted by a visuo-spatial task but not by a secondary verbal task. The converse was true for letter span. These results suggest that the impairment in short-term visual memory resulting from secondary arithmetic reflects a small general processing load, but that the selective interference due to mode of processing is by far the stronger effect. Results are interpreted as being entirely consistent with the notion of a specialized visuo-spatial mechanism in working memory. PMID- 2260494 TI - Eye movement indices of mental workload. AB - Four investigations were carried out to assess the feasibility of using eye movement measures as indices of mental workload. In the first experiment, saccadic extent was measured during free viewing while subjects performed low, moderate and high complexity, auditory tone counting as the workload tasks. The range of saccadic extent decreased significantly as tone counting complexity (workload) was increased. In the second experiment the range of spontaneous saccades was measured under three levels of counting complexity with a visual task that did not require fixation or tracking. The results indicated that the extent of saccadic eye movements was significantly restricted as counting complexity increased. In the third experiment, the effects of practice were examined and decreased saccadic range under high tone counting complexity was observed even when significant increases in performance occurred with practice. Finally, in experiment 4, the first experiment was repeated with additional optokinetic stimulation and the saccadic range was again observed to decrease with tone counting complexity. The results indicated that the extent of spontaneous and elicited eye movements was significantly restricted as counting complexity increased. We conclude that this measure may provide a valuable index of mental workload. PMID- 2260495 TI - Effects of hyperosmotic stimulation and adrenalectomy on vasopressin mRNA levels in the paraventricular and supraoptic nuclei of the hypothalamus: in situ hybridization histochemical analysis using a synthetic oligonucleotide probe. AB - The effects of salt loading and adrenalectomy on arginine vasopressin (AVP) mRNA levels in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus were studied by semiquantitative in situ hybridization histochemistry, using a synthetic oligonucleotide probe and a computer-assisted image analysis system. Salt loading (2% NaCl) for 7 days produced marked increases in AVP mRNA levels in the magnocellular neurons of the PVN, SON, and accessory nuclei. Adrenalectomy caused an increase in AVP mRNA expression in the magnocellular part of the PVN and the expansion of hybridization signals into its medial parvocellular region, where the cell bodies of corticotropin-releasing hormone (CRH) neurons are located. No apparent alteration of AVP mRNA levels was observed in the SON following adrenalectomy. These results indicate that hyperosmotic stimulation and the loss of circulating glucocorticoids had differential effects on AVP gene expression in the PVN and SON, and that the magnocellular PVN and SON neurons responded in different manners to the loss of feedback signals. PMID- 2260496 TI - Exhaled metallic mercury in acatalasemic, hypocatalasemic and normal mice injected with mercury (II) chloride. AB - To clarify the relationship between the catalase activity in mouse organs and the amounts of metallic mercury exhaled, normal, homozygous hypocatalasemic and acatalasemic mice were injected with mercuric chloride. The cumulative amount of metallic mercury exhaled by mice was evidently expressed in the descending order of acatalasemic, hypocatalasemic, and normal mice. Statistically significant differences in the cumulative exhaled metallic mercury levels were observed between acatalasemic and hypocatalasemic mice, between normal and hypocatalasemic mice, and between acatalasemic and normal mice using the method of one way analysis of variance (ANOVA). A linear relationship was obtained through logarithm of catalase activity in the lungs or the blood, and logarithm of the cumulative amount of the exhaled mercury. PMID- 2260497 TI - Changes in the concentrations of urinary proteins after physical exercise. AB - The influence of physical exercise on the urinary excretion of proteins was examined in 17 male high school baseball players. Their urine was collected before and after exercise to determine the concentrations of total protein, albumin, beta 2-microglobulin and creatinine along with the activity of N-acetyl beta-D-glucosaminidase (EC 3.2.1.30). Concentrations of total protein, albumin, beta 2-microglobulin and creatinine increased significantly (p less than 0.01) after exercise, while N-acetyl-beta-D-glucosaminidase activity did not increase. Similar results were obtained when the concentrations of these urinary components were calculated on the basis of a urinary density of 1.024, and when they were expressed relative to the amount of creatinine. Positive correlations were seen among total protein, albumin, beta 2-microglobulin and creatinine concentrations, but not between the beta 2-microglobulin concentration and N-acetyl-beta-D glucosaminidase activity. Isoenzyme activities of N-acetyl-beta-D-glucosaminidase in the urine were determined by electrophoresis on cellulose acetate plates. After exercise, the A-form increased slightly, and the B-form decreased slightly, but these changes were not statistically significant. PMID- 2260498 TI - Senile delirium with special reference to situational factors and recurrent delirium. AB - Factors initiating senile delirium were examined in 129 elderly inpatients (65 years or older). Sixty-eight patients were males and 61 females, with a mean age of 76.3 years. Delirium developed in most cases on the first two days of admission in the hospital, and the admission appeared to be a key factor precipitating delirium in about 30% of the patients. Delirium resolved or improved in 80% of the patients, but usually persisted in patients with dementia. Senile delirium tended to reappear repeatedly in patients whose episode of delirium lasted for more than 2 weeks, was associated with dementia, or had a prior history of delirium. PMID- 2260500 TI - Primary non-Hodgkin's lymphoma of the rectum: a case report. AB - A rare gastrointestinal tract neoplasm, primary non-Hodgkin's B-cell lymphoma in a 39-year-old, asymptomatic woman is described. The tumor was originally localized in the rectum without evidence of any other lymphoma-involved organ and treated by curative surgical procedure associated with postoperative chemotherapy. PMID- 2260499 TI - Duodenal mucosal hemodynamics in patients with liver cirrhosis. AB - Clinical studies show that patients with liver cirrhosis associated with portal hypertension have a high incidence of duodenal ulcer and duodenitis. However, little information is available concerning pathophysiological process of such duodenal diseases in liver cirrhosis. Hemodynamics of the duodenal mucosa was studied in cirrhotics with esophageal varices (68 cases) and in noncirrhotics with non-ulcer dyspepsia (37 cases) as well. In each group, hemoglobin concentration in the peripheral venous blood was measured, and mucosal hemodynamics was examined in 4 regions of the duodenum by endoscopic reflectance spectrophotometer. No significant intergroup difference was noted in the mean age or sex ratio. Hemoglobin concentration in the peripheral venous blood was significantly lower (p less than 0.01) in the cirrhotics. There were no significant intergroup differences in duodenal mucosal blood volume. However, the cirrhotics showed significantly lower oxygen saturation of hemoglobin in all regions of the duodenum (p less than 0.01). These results show that the cirrhotics with esophageal varices had relative increase in blood volume and decrease in oxygen saturation of hemoglobin in the duodenal mucosa. Such microcirculatory disturbances seem to predispose liver cirrhosis patients to duodenal injury. PMID- 2260501 TI - A variant Philadelphia chromosome (Ph1) positive chronic myelocytic leukemia. AB - A rare case of variant Philadelphia (Ph1) chromosome positive [46, XX, t (9; 22) (q34; q11), inv (9) (9q22; 22q13)] chronic myelocytic leukemia (CML) was described. The patient, 73 years old female, was hospitalized to our hospital because of leukocytosis. Hematological findings corresponded to those of CMLs. However, this case lacked hepatosplenomegaly. Southern blot analysis using a 3 breakpoint cluster region (bcr) probe revealed a bcr rearrangement. The patient has been in the chronic phase for sixteen months without treatment. Clinical and chromosomal changes are under observation in order to get accumulate data for a pathophysiological analysis of variant Ph1 positive CMLs. PMID- 2260502 TI - Treatment of recurrent common warts with one low dose of intralesional natural human leukocyte interferon alpha. AB - Nine patients with recurrent and long lasting common warts were treated with intralesional Hu-IFN-alpha. The schedule was a single dose per wart, ranged between 10(5) and 2 x 10(5) IU. Placebo was also administered in 3 of these patients. Complete remission was observed in 7 of the 9 patients. The pattern of warts involution and the possible interferon mechanism of action are discussed. A significant pain relief, produced by interferon injection was observed in the patients with plantar warts and in one patient with subungueal wart. PMID- 2260503 TI - Alpha interferon plus thymopentine in treatment of HBV and/or HDV positive patients undergoing liver transplant. AB - Infection by hepatitis B (HBV) and/or delta virus (HDV), is the most frequent acquired pathology in patients affected by end-stage hepatic disease, candidates for liver transplant. To reduce the risk of virus reactivation after surgery, we used alpha Interferon (IFN) therapy in patients who were HBV-DNA and/or HDV-RNA positives before transplant. Our protocol included alpha IFN at low dosage associated to a thymic hormone that seems to have a synergistic activity with IFN. We have evaluated in four patients, affected by post hepatitic end-stage liver disease, the outcome of HBV and HDV markers in relation to immunological response during treatment. Our interest has been focused on monocyte and natural killer cytotoxic activity. The data show that all patients, before starting therapy, had evidence of active phase viral replication. They also displayed low values of the immunological parameters tested. The study of viral markers showed decrease of HBV and HDV in all patients. The relation between viral markers and natural killer and monocyte cytotoxicity was very interesting; during the treatment we observed a marked increase of both activities. At the same time no relevant modifications in the other immunological parameters tested were found. PMID- 2260504 TI - Measurement and partial characterization of an interleukin-2 inhibitor (IL-2-IN) in human urine. AB - We observed a human urine-derived protein complex (IL-2-IN) which competitively inhibits interleukin-2 (IL-2) dependent murine lymphocyte proliferation. Measurements of urinary IL-2-IN have been used to stratify the immune response of patients to bacteria in the bladder. Partial characterization of IL-2-IN indicates that it is a heat-stable, 75 kDa complex comprised of interleukin-2 bound to another protein(s). Although the IL-2-IN complex is stable in physiologic buffers, the complex can be disrupted using acidic or low-ionic strength buffers, thereby liberating IL-2. IL-2-IN activity is susceptible to bacterial and endogenous urinary proteolysis. The IL-2 bound in the IL-2-IN complex cannot be detected using a double monoclonal antibody radioimmunoassay for IL-2. Unlike other IL-2 binding proteins, the IL-2 binding protein of the IL 2-IN complex is not a soluble interleukin-2 receptor. A modification of the bioassay for interleukin-2 activity is the method of choice for the detection and quantification of urinary IL-2-IN. PMID- 2260505 TI - The vitamin E distribution in serum, liver, adipose and muscle tissues in the pig during depletion and repletion. AB - This study was designed to examine the storage capacity for vitamin E in liver, adipose tissue and skeletal muscle of growing pigs during a period of supplementation and of depletion. Therefore, biopsy specimens of these tissues and samples of serum were frequently taken from 7 pigs throughout the experimental period. After a 7-week period on a diet highly supplemented with vitamin E (405 mg/kg), a significant increase (p less than 0.001) in the concentration of this vitamin was observed in all tissues sampled. The highest level (102.9 +/- 26.2 mg/kg) was observed in the liver. After 2 days of depletion the concentration of vitamin E in the liver had fallen by 80%, whereas the concentration in the fat and muscle remained unchanged during 1 week of depletion. The serum vitamin E value rose significantly (p less than 0.001) after 1 week on the supplemented diet and then remained at about 7 mg/l throughout the supplementation period and decreased (p less than 0.001) after 2 days on a nonsupplemented diet. Generally, the serum vitamin E levels among growing pigs are between 2 and 3 mg/l. The results show that the serum and liver values were correlated when the serum level was within this range. Moreover, it is clearly demonstrated that the concentrations of vitamin E in serum and liver reflect the immediate nutritional status of the animal, whereas the vitamin concentrations in adipose and skeletal muscle tissue reflect its long-term nutritional history. PMID- 2260506 TI - Adenosine deaminase and porcine meat quality. II. Effects of adenosine analogues on plasma free fatty acids, glucose and lactate in pigs representing high and low adenosine deaminase red cell activity. AB - The adenosine analogues 5'-(N-ethyl) carboxamidoadenosine (NECA) and N6 (phenylisopropyl) adenosine (R-PIA) were shown to differ in their effect on the plasma level of free fatty acids (FFA), glucose and lactate in pigs representing low (Ada 0) and high (Ada A) red cell adenosine deaminase activity. At the same dosage range (0.001-0.005 mg/kg) R-PIA produced a much stronger suppression of the FFA level than NECA, indicating that A1 adenosine receptors predominate in porcine adipose tissue. Pretreatment with 8-phenyltheophylline completely abolished the antilipolytic effect of both adenosine analogues. NECA in contrast to R-PIA elevated the blood glucose concentration, suggesting that A2 adenosine receptors are involved in the stimulation of glycogenolysis. This effect of NECA was not altered by a beta-adrenoceptor blockade providing evidence for a direct effect of adenosine on glycogenolysis. Whereas the changes in plasma FFA following NECA administration were of similar magnitude in Ada A and Ada 0 pigs, the changes in the blood glucose concentration were different in these two groups of pigs. PMID- 2260507 TI - A study on the survival of Taenia saginata eggs on soil in Denmark. AB - The infectivity of Taenia saginata eggs exposed to environmental conditions on a natural soil surface in Denmark was studied by feeding the eggs to susceptible calves, followed by determination of the number of cysts developed. The results indicated that a small proportion of the eggs remained infective for 6 1/2 months, but not for 9 1/2 months when deposited in May 1986, and for 5 1/2 months but not for 8 1/2 months when deposited in September 1987. Viability of eggs was tested in vitro and compared with infectivity obtained in calves. PMID- 2260508 TI - Bovine cysticercosis in Denmark. A study of possible causes of infection in farms with heavily infected animals. AB - Epidemiological studies were made on 14 farms from which, during a 2 year period, 38 cattle had been condemned at slaughter, due to massive infections with Cysticercus bovis. By on-site investigations and interviews, attempts were made to identify the transmission routes of Taenia saginata eggs from human faeces into the environment and further on to cattle. The most frequent sources of infection were found to be sludge from septic tanks illegally applied on pasture or crops, in some cases after having been mixed with animal slurry. Animals in permanently housed herds were infected through the fodder or by contamination of the indoor environment by such slurry containing Taenia eggs. Other herds were infected by grazing pastures in close proximity to municipal sewage treatment plants. In contrast to earlier Danish observations, application on farmland of sewage sludge from municipal treatment plants was not involved in any of the reported outbreaks. This apparent change coincides with the implementation of more restrictive legislation for the agricultural use of sewage sludge in Denmark. PMID- 2260509 TI - Growth characteristics of Staphylococcus aureus and Escherichia coli in whey from sequentially infected milk. AB - The growth of Staphylococcus aureus and Escherichia coli was followed in bovine whey samples which had been prepared from milk previously incubated with cultures of S. aureus or E. coli. Staphylococcal strains were divided into 2 groups according to their ability to form compact or diffuse colonies on serum soft agar, which is related to the absence or presence of capsule respectively. The growth of compact staphylococci was dependent on the bulk tank milk used whereas diffuse colony forming staphylococci grew equally well in all bulk milk, also in all inoculated milk. The growth of E. coli was markedly enhanced in whey samples prepared from milk preincubated with staphylococci. However, clear growth inhibition was seen with E. coli and S. aureus strains when grown in whey prepared from milk preincubated with E. coli. Results indicate that the growth promotion of pathogens due to compositional changes in milk are of importance during the course of infection because the growth pattern on staphylococci is dependent on these compositional changes. The growth-inhibitory effects caused by E. coli may explain difficulties in isolating this organism. PMID- 2260510 TI - Three types of acrosomal aberrations of bull spermatozoa and their relation to fertility. AB - The effect of acrosomal aberrations of the spermatozoa of Finnish Ayrshire bulls on the corrected non-return rate within 60 days of the first 500 inseminations was studied. The material consisted of sperm samples examined by the artificial insemination societies. All samples had been accepted for use in artificial insemination. One Giemsa-stained slide was studied for each of the 95 bulls concerned. Samples showing distinct acrosomal defects were studied by electron microscopy. Three different types of acrosomal aberration were found. One was obviously associated with subfertility in all 6 bulls in which it was detected. PMID- 2260511 TI - Uterine involution in Finnish dairy cows. AB - The effect of parity on the cervical and uterine involution was studied in 79 Finnish dairy cows on a research farm. The cows were examined clinically by rectal palpation 3 times a week during 8 weeks postpartum. The diameters of the cervix and uterine horns were estimated manually. The parous uterine horn was compared with the non-parous one. The results were separately analysed in primiparous cows (n = 18) and in those with the third calving (n = 61). A significant difference (p less than 0.001) between the parous and non-parous uterine horns was obtained until 21 days. Thereafter, involution still continued and equal diameters for the horns were not found until 5 weeks after parturition. A decline of the cervical diameter continued until 30 days after the delivery. The parity had no significant effect on the swiftness of uterine or cervical involution. However, in multiparous cows the cervical diameter remained larger than that in the primiparous animals still at 8 weeks postpartum. PMID- 2260512 TI - A preliminary study of uterine derived polymorphonuclear cell function in mares with chronic uterine infections. AB - From 6 mares with chronic uterine infection, polymorphonuclear neutrophils (PMNs) were obtained from the uterus. In order to recover an adequate number of viable PMNs, 0.1% oyster glycogen was infused into the uterus as a mild irritant 12 h prior to the uterine flushing. Phagocytosis and chemotaxis of the uterine derived PMNs were determined. The supernatant from the uterine flushing was compared with autologous serum for its capacity as an opsonin and chemoattractant. There was a significant increase of both phagocytosis and chemotaxis when autologous serum was used compared with the supernatant from the uterine flushing. This study indicates that autologous serum has a greater opsonizing capacity than uterine secretion from mares with chronic uterine infection. Since all mares conceived following this study, the use of oyster glycogen was not considered to have deleterious effect on the uterine mucosa. PMID- 2260513 TI - Some effects of gram-negative bacterial endotoxin and its importance as a contaminator of biological preparations. AB - The purpose of this study was to establish a model which can be used to examine the biological response to Salmonella typhimurium endotoxin in both anaesthetized and unanaesthetized rabbits, and then compare this response to that of rabbits injected with an endotoxin-contaminated biological preparation. The parameters used to evaluate the biological response included total white blood cell and differential counts, 15-ketodihydro-PGF2 alpha concentration, and rectal temperature. Unanaesthetized groups of rabbits received 1000, 100, 10, or 1 ng/kg of the endotoxin via intravenous injection (i.v.); the anaesthetized group of rabbits received 100 ng/kg endotoxin i.v. (anaesthesia induced with Hypnorm). In addition, groups of rabbits were treated under anaesthesia with Pharmacia Chiron's recombinant human Cu/Zn superoxide dismutase (SOD) (10 mg/kg body weight = 1.6 endotoxin units (EU)/kg) or Grunenthal's bovine SOD (two doses: 10 mg/kg = 400 EU/kg, or 50 mg/kg = 2000 EU/kg). Results demonstrated that at the lower doses of endotoxin (10 and 1 ng/kg) and r-hSOD (10 mg/kg), no leukopenia was observed. There was however a slight shift in the leukocyte population so that polymorphonucleocytes increased and monocytes decreased in number. Rabbits treated with higher doses of endotoxin (1000 and 100 ng/kg) showed many of the common signs of endotoxemia, including leukopenia, increased prostaglandin metabolite levels, and increased body temperature, as did the rabbits treated with endotoxin-contaminated bSOD. There was a definite dose-dependency, with the higher dose of bSOD giving a more marked rise in all parameters. These findings indicate that use of this or other endotoxin-contaminated biological preparations in live-animal experiments could produce erratic, and therefore unreliable, results. PMID- 2260514 TI - Biological responses of sheep treated with endotoxin-contaminated superoxide dismutase and endotoxin preparations. AB - The purpose of this study was to evaluate the biological response of sheep to different doses of endotoxin and endotoxin-contaminated enzyme preparations. The enzyme used in this experiment was superoxide dismutase (SOD), as it is currently being used in many different experiments and because several preparations were found to be heavily contaminated with endotoxin. A group of ewes were injected intravenously with a variety of different treatments. Peripheral blood was used to determine the total number of leukocytes, a differential cell count to find out the numbers of polymorphonucleocytes (PMN) and monocytes (M), and to measure the concentration of 15-ketodihydro-PGF2 alpha. In addition, rectal temperature was recorded. Treatments included saline (control), Pharmacia-Chiron's Cu/Zn-SOD (r-hSOD, 8 mg/kg), Sigma's bovine SOD (bSOD, 8 mg/kg), Grunenthal's bSOD (8 mg/kg), various doses of Salmonella typhimurium endotoxin (1000, 200, 100, 50, 20, 10, 5, and 1 ng/kg), and a mixture of endotoxin (200 ng/kg) plus r-hSOD (8 mg/kg). Results indicate that sheep react to endotoxin-contaminated SOD preparations with an endotoxemia which is similar to that seen in animals receiving endotoxin alone. This endotoxemia includes, among other things, a rise in rectal temperature, a peak in the PGF2 alpha metabolite, and an increased PMN/M ratio. Endotoxin administered at doses of 50 to 200 ng/kg also caused the expected signs of endotoxemia. At 1000 ng/kg endotoxin actually led to a decreased rectal temperature. This may be due to a type of endotoxemic shock, resulting in a decrease in peripheral blood circulation. Low doses of endotoxin (10, 5, and 1 ng/kg) caused a leukocytosis via increases in PMN; no greater changes in rectal temperature or the PGF2 alpha metabolite were noted. The combination of r-hSOD with 200 ng/kg of endotoxin caused an endotoxemia similar to that caused by 200 ng/kg of endotoxin alone. In conclusion, if an endotoxin contaminated SOD-preparation was used to study the efficacy of SOD, there would be a serious risk of interaction by the endotoxins. In such a case it would be impossible to distinguish the effects of the endotoxin from those of the preparation itself. It is therefore important that researchers are alert to the problem of endotoxin contamination. PMID- 2260515 TI - Prevalence of antibodies to Toxoplasma gondii in cats, dogs and horses in Sweden. AB - Samples of serum or plasma taken during 1986 and 1987 from 244 pet cats, 303 dogs and 219 horses, randomly selected among animals referred to the Animal Clinics of the Swedish University of Agricultural Sciences, were screened by enzyme-linked immunosorbent assay (ELISA) for antibodies to Toxoplasma gondii. 42% of cats, 23% of dogs and 1% of horses examined were found seropositive. PMID- 2260516 TI - A method for monitoring antibodies against staphylococcal DNases. AB - When small amounts of DNase produced by Staphylococcus aureus, S. intermedius or S. hyicus were added to Toluidine Blue DNA Agar (TDA), a medium for demonstration of staphylococcal antiDNases was produced. By applying this medium in microtitre plates, a test system for titration of staphylococcal antibodies in serum samples was developed. A colour change from blue to pink could be observed when the DNase was allowed to act, i.e. when no staphylococcal antiDNases were present in the samples. When serum with neutralizing antibodies were applied, no colour change developed. An end-point could easily be demonstrated in dilutions of the serum. A description of the method, including certain of its limitations is given. PMID- 2260517 TI - A study on primiparous sows of the ability to show standing oestrus and to ovulate after weaning. Influences of loss of body weight and backfat during lactation and of litter size, litter weight gain and season. AB - The ability to show standing oestrus and to ovulate within 10 days of weaning was studied in 240 purebred Swedish Yorkshire primiparous sows, fed according to a conventional feeding regime during lactation. The sows were weighted and backfat depth was recorded at farrowing and at weaning. Oestrus control was performed daily and blood samples for determination of plasma progesterone were drawn regularly in 205 sows. The distribution among the sows of the first standing oestrus after weaning had 2 peaks. The first peak occurred within 10 days of weaning and the second 24-30 days after weaning. Twelve per cent of the sows ovulated without showing standing oestrus within 10 days of weaning and 4% had an anovulatory first oestrus within the same time. Significant differences in age at farrowing and in loss of weight and backfat during lactation were found between sows which both showed standing oestrus and ovulated within 10 days of weaning and sows which neither showed standing oestrus, nor ovulated within the same time. The season during which weaning occurred significantly influenced the ability to show standing oestrus and ovulate within 10 days of weaning. Among the sows which both showed standing oestrus and ovulated within 10 days of weaning, significant positive correlations were found between weight loss, litter size, litter weight gain and the interval from weaning to first standing oestrus. PMID- 2260518 TI - Epidemiological and genetical studies in Norwegian pig herds. I. Design of a disease recording system. AB - The study was based on 70 pig herds in the south-eastern part of Norway during the period from 1984 to 1986. The purpose was to design a health card system based on individual disease records covering diseases in sows, piglets and slaughter pigs. It is concluded that individual health records on a herd basis may well be suited for use in epidemiological and genetical studies of disease frequencies and disease resistance. Feedback of results to farmers and veterinarians seems to be important for satisfactory follow-up in the herds. PMID- 2260519 TI - Antibodies against Staphylococcus aureus DNase in goat serum. PMID- 2260520 TI - Inheritance of bovine spinal muscular atrophy. PMID- 2260521 TI - Child-resistant caps keep out adults too. PMID- 2260522 TI - When natural disaster strikes. PMID- 2260523 TI - Geriatric education: a fundamental requirement for pharmacy practice. PMID- 2260524 TI - OTC labels: can consumers read and understand them? PMID- 2260525 TI - The legalization of drugs of abuse: can the health care system handle it? PMID- 2260526 TI - Overview of infectious diseases, Part 2. AB - The choice of drug therapy in the treatment of infectious disease depends on many factors, including the probable sensitivity of likely pathogens and previous efficacy of the agent. Pharmacokinetic factors are crucial since good in vitro results cannot predict in vivo success unless the drug is present in effective concentration at the infection site. Combination therapy can be used in certain situations to improve the chances of clinical success. Part 3 of this series will conclude the discussion of drug therapy. The general manifestations of and recovery process from infectious diseases will also be discussed. PMID- 2260527 TI - Auditory epithelial migration on the human tympanic membrane: II. The existence of two discrete migratory pathways and their embryologic correlates. AB - The pathways of movement of dye-markings on the tympanic membranes of 30 ears of 15 volunteers were investigated by photography with a Hopkin's rod. Two discrete pathways were identified. Movement on the pars tensa was centrifugal in all directions from the edge of the handle of malleus surface. This supported our previous suggestion that pars tensa epithelial migration is based on growth of the meatal plate. Movement on the more central part of the handle surface itself, however, was always upwards to the pars flaccida epithelium and then, with all dye on the latter, in a posterosuperior direction only. The covering epithelium of the pars flaccida/handle of malleus arises from the fundus of the early embryonic external canal. To explore the possibility that its migration may also commence early, the fundus was examined histologically in 12 embryo ears. It was shaped like an inverted pear to conform to the primordial head of the malleus above and its handle below. There was distinct flattening of the whole fundal epithelium in contrast to the side wall of the external canal, lending support to the concept of a primordial flux of epithelium in the main fundus and its inferior extension. The meatal plate grew from the rim of the fundus producing the pars tensa and deep external canal epithelia. This process, however, was not associated with significant cytologic alterations or increased expression of the human proliferation antigen, Ki-67, at that rim. This suggests that the pars tensa epithelium grows and moves without the active involvement of the epithelium of the pars flaccida/handle of malleus. PMID- 2260528 TI - The effect of chronic hypercalcemia or hypocalcemia on the follicular and parafollicular cells in rat thyroid gland. AB - In three experiments of 30 weeks' duration, 93 adult female Wistar rats received controlled amounts of calcium with food and water, to produce a state of either hypercalcemia or hypocalcemia. A systematic stereological analysis of the thyroid glands and a radioimmunological analysis of thyroxine, triiodothyronine, and thyrotropine were performed. In the hypercalcemic rats, a reactive hyperplasia of the parafollicular cells was established; this was accompanied by morphological and biochemical signs of hyperfunction of the follicular cells, despite a reduced central stimulation by thyrotropin. In the hypocalcemic animals, no quantitative morphological changes in the parafollicular cells were observed; however, morphological and biochemical signs of hypofunction of the follicular cells were obvious, despite stronger central stimulation by thyrotropin. It is concluded that the extrinsic regulation of follicular cells by the blood calcium level is stronger than the intrinsic regulation by hypothalamo-hypophyseal hormones. PMID- 2260529 TI - Changes in numbers of pancreatic acinar cell nuclei and in DNA content during raw soya flour feeding in mice. AB - Nuclei of pancreatic cells were isolated by trypsin-detergent digestion of fresh tissue and stained with propidium iodide, and nuclear DNA was measured by flow cytometry. Samples were isolated from mice fed either chow or raw soya flour (RSF) for periods ranging from 1 day to 48 weeks, beginning at 4 weeks of age. In chow-fed mice, the pancreas contained about 80% diploid (2N) and 20% tetraploid (4N) cells at the start of the study, but tetraploidy gradually increased to about 40% 2 weeks later (6 weeks of age) and remained at this level from that time onwards. Low levels of octaploid nuclei (8N) were also present in some animals after 2 weeks. In RSF-fed mice, about 20% tetraploid nuclei were also present for 1 and 2 days after starting RSF, but by 4 days tetraploidy had increased significantly to 40% and by 14 days had further increased to 50%. This level was significantly higher than that seen in chow-fed animals and was maintained for up to 48 weeks. Significantly higher numbers of octaploid nuclei were also present in the RSF-fed animals. In both chow- and RSF-fed mice, most cells were mononuclear, averaging 70% in chow-fed and 64% in RSF-fed animals. This difference was significant. This study shows that the mouse pancreas differs from the rat pancreas in the absence of a large population of binucleate acinar cells and the presence of considerable nuclear tetraploidy. Raw soya flour feeding leads to significant changes in these features, but in this species these changes do not appear to predispose to neoplasia. PMID- 2260530 TI - Innervation of the guinea pig spleen studied by electron microscopy. AB - The innervation of the guinea pig spleen was investigated by electron microscopy. Unmyelinated nerve fibers in the capsulotrabecular and arterial systems were found to contain large and small granular and small agranular synaptic vesicles in their terminals and are thought to be sympathetic adrenergic in nature. They influence the contraction of the smooth muscle cells by diffusion innervation in these systems. These nerve terminals were also scattered in both the red and the white pulp. Pulp nerves wrapped by Schwann cells were further enclosed by myofibroblastic reticular cells. This condition revealed that the pulp nerves pass through the connective-tissue spaces of the reticular fibers, which contain elastic fibers, collagenous fibrils, and lamina densa-like materials of the usual basement laminae. One of the target cells for the pulp nerves is considered to be the myofibroblastic reticular cell in the reticular meshwork. Neurotransmitter substances released from the naked adrenergic nerve terminals travel through the reticular fibers and may play a role, by both close association innervation and diffusion innervation, in the contraction of reticular cells to expose the reticular fibers. At the exposed sides, connective-tissue elements of the reticular fibers are bathed with blood plasma, and the included naked nerve terminals, devoid of Schwann cells but with basement laminae of these cells, face free cells at some distance or are in close association with free cells, especially lymphocytes, macrophages, and plasma cells. The close ultrastructural relationship between the naked adrenergic nerve terminals and immunocytes strongly suggests that there is an intimate relationship between the immune system and the sympathetic nervous system through both close association innervation and diffusion innervation. Thus splenic adrenergic nerves of the guinea pig may play a triple role in 1) contraction of smooth muscle cells to regulate blood flow in the organ, 2) induction of the exposure of reticular fibers by contraction of the reticular cells in order to form a close relationship of the nerve terminals with the immunocytes, and 3) subsequent neuroimmunomodulation of the immunocytes. PMID- 2260531 TI - The eye of the magellanic penguin (Spheniscus magellanicus): structure of the anterior segment. AB - We undertook a light and scanning electron microscopic study of the eye in the Magellanic penguin (Spheniscus magellanicus). The anatomical peculiarities of the eyeball shape in Sphenisciformes have been previously described by others; here, we show that they are accompanied by several modifications in the organization of the anterior segment of the eye. The main change was found in the portion of opaque sclera extending from the cornea to the anterior border of the scleral ossicles, which was much broader than in other avian eyes. This scleral region was made of a very dense fibrous tissue and was as difficult to cut as the ossicles. The corneo-scleral boundary was also different from that of other birds, since the aqueous humor channel and the pectinate ligament were located 1.0-1.5 mm posterior to the cornea. The osseous ring was formed by 13 bones, including three pairs of over- and underplates. There was a single ciliary muscle, with meridionally oriented striated fibers. They were inserted on a circumference along the boundary between the fibrous sclera and the ossicles, far away from the wall of the aqueous humor channel. On their posterior end, the muscle fibers formed a tendinous structure attached to the inner surface of the sclera and to the outer surface of the ciliary body. Only short zonular fibrils were observed. These anatomical features are probably relevant for the adaptation of penguin eyes to vision on land and in the aquatic environment. PMID- 2260532 TI - Three-dimensional cytoarchitecture of the media of arteriovenous anastomoses in the rabbit ear. AB - Arteriovenous anastomoses in the rabbit ear were examined with scanning electron microscopy to elucidate the structural differentiation of the media of the shunt. Arterial, intermediate, and venous segments in the shunt and two layers of the media in the intermediate segment were differentiated based on cell shape and cell organization. In the arterial segment, smooth muscle cells were spindle shaped, either elongated or short, with a few branches, and were arranged circularly or diagonally with respect to the vessel's long axis. There were also stellate muscle cells with radiating processes. In the intermediate segment, the smooth muscle cells of the outer layer of the media were also arranged circularly and resembled the elongated cells in the arterial segments, but they were more irregular in shape and had more processes than those of the arterial segment. The epithelioid cells of the inner layer of the media were oval or polygonal and oriented irregularly with respect to the vessel's long axis, clustering to form longitudinal plicae. The smooth muscle cells of the venous segment were flat with many lateral processes and formed a thin, discontinuous layer. The smooth muscle cells in the arterial segment and those of the outer layer of the intermediate segment exhibited a highly rugged surface texture, indicating their strong contractility; the epithelioid cells and the smooth muscle cells in the venous segment exhibited a generally smooth surface, indicating less contractility. The intermediate segments were supplied with a dense nerve plexus. The intermediate segments, therefore, may be actively involved in the regulation of blood flow under neuronal influence. PMID- 2260533 TI - Prenatal development of the human nucleus ambiguus during the embryonic and early fetal periods. AB - The ontogenetic development of the nucleus ambiguus was studied in a series of human embryos and fetuses ranging from 3 to 12.5 weeks of menstrual age (4 to 66 mm crown-rump length). They were prepared by Nissl and silver methods. Nucleus ambiguus neuroblasts, whose neurites extend towards and into the IXth and rostral Xth nerve roots, appear in the medial motor column of 4-6-week-old embryos (4.25 11 mm). These cells then migrate laterally (6.5 weeks, 14 mm) to a position near the dorsal motor nucleus of X. At 7 weeks (15 mm), nucleus ambiguus cells begin their migration, which progresses rostrocaudally, into their definitive ventrolateral position. The basic pattern of organization of the nucleus is established in its rostral region at 8 weeks (22.2-24 mm) and extends into its caudal region by 9 weeks (32 mm), when its nearly adult organization is evident. Cells having the characteristics of mature neurons first appear rostrally in the nucleus during the 8.5-9-week period (24.5-32 mm), gradually increase in number, and constitute the entire nucleus at 12.5 weeks (65.5 mm). Definitive neuronal subgroups first appear at 10 weeks (37.5 mm) in the large rostral nuclear region. These features suggest that the human nucleus ambiguus develops along a rostrocaudal temporospatial gradient. Evidence indicates that function of nucleus ambiguus neurons, manifested by fetal reflex swallowing, occurs after the cells migrate into their definitive position, establish the definitive nuclear pattern, and exhibit mature characteristics. PMID- 2260534 TI - Measurement of total risk of spontaneous abortion: the virtue of conditional risk estimation. AB - The concepts, methods, and problems of measuring spontaneous abortion risk are reviewed. The problems touched on include the process of pregnancy verification, the changes in risk by gestational age and maternal age, and the presence of induced abortions. Methods used in studies of spontaneous abortion risk include biochemical assays as well as life table technique, although the latter appears in two different forms. The consequences of using either of these are discussed. It is concluded that no study design so far is appropriate for measuring the total risk of spontaneous abortion from early conception to the end of the 27th week. It is proposed that pregnancy may be considered to consist of two or three specific periods and that different study designs should concentrate on measuring the conditional risk within each period. A careful estimate using this principle leads to an estimate of total risk of spontaneous abortion of 0.33. PMID- 2260535 TI - Fire fighters and risk of cancer: an assessment and overview of the epidemiologic evidence. PMID- 2260536 TI - Vasectomy and the risk of prostate cancer. AB - An unexpected association between history of vasectomy and increased risk of prostate cancer emerged when multiple comparisons were carried out in data collected from 1976-1988 in a US hospital-based case-control study of many diseases and exposures. The association was assessed in detail in these data, in a comparison of 220 men with first episodes of prostate cancer with 571 noncancer controls and 960 cancer controls. The age-adjusted relative risk of prostate cancer was 5.3 (95% confidence interval 2.7-10) when noncancer controls were used and 3.5 (95 percent confidence interval 2.1-6.0) when cancer controls were used. The magnitude of the relative risk estimate appeared to be unrelated to the length of the interval after vasectomy. Allowance for several factors did not alter the estimates, but we did not have information on testosterone level or sexual activity, which may have been confounding factors. The association was stronger among men most likely to have been under more intensive medical surveillance; selective detection of asymptomatic cancer in such men would have led to an excess of cases. Further studies are needed to rule out chance, bias from medical surveillance, and uncontrolled confounding as explanations for the finding. PMID- 2260537 TI - Vasectomy and prostate cancer risk. AB - To assess the hypothesis that a history of vasectomy is a risk factor in the etiology of prostate cancer, the authors conducted a case-control study at Roswell Park Memorial Institute, Buffalo, NY, between 1982 and 1988. From epidemiologic data routinely collected from entering patients, information on vasectomy history and other data were obtained for 614 patients with prostate cancer and 2,588 comparable control subjects with cancer at another site. Age specific and age-adjusted relative risks were calculated. Increased risk (relative risk = 1.7, 95% confidence interval 1.1-2.6) was found for reporting vasectomy at any age. Age-adjusted relative risk of 2.2 (95% confidence interval 1.0-4.6) was observed for men who reported vasectomy 13-18 years before diagnosis. A significant trend in the association of years since vasectomy and risk also was observed. Cases and controls were found to be nearly identical with respect to education, income, race, marital history, and number of children. A difference in smoking histories of cases and controls was found not to confound the observed associations. These data may suggest the importance of further epidemiologic and biologic research on vasectomy as a risk factor for prostate cancer. PMID- 2260538 TI - Trends in the incidence of malignant melanoma in Sweden, by anatomic site, 1960 1984. AB - This study was based on 15,376 patients in Sweden with cutaneous malignant melanoma diagnosed during the 25-year period 1960-1984. Trunk melanoma increased substantially during that period among men, with age-standardized rates rising from 1.1 to 7.0 per 10(5). Among women, the greatest increases occurred in melanoma of the upper extremity (rising from 0.4 to 2.3), lower extremity (rising from 1.6 to 4.4), and trunk (rising form 0.6 to 3.1), but the rates for the latter two sites seemed to level off after 1978. Multivariate analyses showed that models based on a common parameter ("drift"), including linear birth cohort and/or time periods effects, were significantly superior to simple age models for explaining incidence trends for each separate site. Further, in men with melanoma of the trunk and upper and lower extremities, birth cohort effects had significant effects compared with drift. In contrast, in women, time period effects were a significant improvement on drift for melanoma of the trunk and lower extremity. The relative risk of malignant melanoma among men leveled off in later-born cohorts for all separate sites. A similar trend was found in women, except for melanomas of the trunk, in which the increase in relative risk persisted. The results indicate sex-specific differences in temporal trends of exposure to factors causing malignant melanoma. PMID- 2260539 TI - Cancer risks in Swedish Lapps who breed reindeer. AB - Cancer risks during the period 1961-1984 were studied in a cohort of 2,034 Swedish reindeer-breeding Lapps, a unique group whose culture and life-style differ considerably from those in the rest of the Swedish population. A total of 100 cases of cancer were observed versus 163 expected. Statistically significantly decreased risks were found for cancers of the colon, respiratory organs, female breast, male genital organs, and kidneys, and for malignant lymphomas. The stomach was the only site with a significantly increased risk. Reindeer-breeding Lapps have ingested fallout products via the lichen-reindeer man food chain since the 1950s. However, no increased risk was found for the cancer sites considered to be most sensitive to radiation. PMID- 2260540 TI - The relation between body mass index and plasma total cholesterol in a multiracial sample of US schoolchildren. AB - The relation between body mass index expressed as weight in kilograms divided by height in meters cubed (weight (kg)/height (m3)) and plasma total cholesterol was assessed in a sample of 11,389 US schoolchildren, aged 5-18 years, between 1984 and 1989. Among whites and Hispanics, a statistically significant nonlinear relation was found between weight (kg)/height (m3) and plasma total cholesterol. Mean cholesterol values increased exponentially above the 50th percentile of body mass index. Additionally, mean cholesterol levels as well as the odds of hypercholesterolemia (total cholesterol value greater than 180 mg/dl) were highest among children with weight (kg)/height (m3) values above the 95th percentile. Among black children, weight (kg)/height (m3) did not appear to be related to plasma total cholesterol. Possible explanations as well as public health implications of these findings are discussed. PMID- 2260541 TI - Use of vitamin and mineral supplements: demographics and amounts of nutrients consumed. The 1987 Health Interview Survey. AB - Data from the 1987 National Health Interview Survey show that 51.1% of the adults aged 18-99 years in the United States consumed a vitamin/mineral supplement in the past year, but that only 23.1% did so daily. Whites, women, and older individuals were more likely than blacks, men, and younger individuals to consume supplements regularly. Multivitamins were the most commonly consumed supplement, followed by vitamin C, calcium, vitamin E, and vitamin A. Results suggest that supplementation practices have changed little since the 1970s. Results regarding the amounts of nutrients obtained from supplements show that a food frequency type of methodology collects reasonably accurate data reflecting intake of supplements over the past year. Few, if any, individuals were consuming nutrients in amounts considered toxic. Although vitamin and mineral supplementation is a common health habit, it appears not to pose a significant health risk for most of the population. PMID- 2260542 TI - Risk factors for carpal tunnel syndrome. AB - Between September 1983 and July 1985, a case-control study was performed of carpal tunnel syndrome risk factors in the general population of Maastricht, The Netherlands, and some surrounding villages. Twenty-eight of the 501 participants were found to suffer from carpal tunnel syndrome. These 28 were added to a series of 128 consecutive carpal tunnel syndrome patients from the same area. The 156 (131 women and 25 men) subjects in whom carpal tunnel syndrome had been diagnosed on the basis of clinical history and neurophysiologic testing were compared with the remaining 473 (310 women and 163 men) subjects. After adjustment for age and sex, the following carpal tunnel syndrome risk factors could be identified: activities with a flexed wrist or with an extended wrist (exposure-related increased risk), hysterectomy without oophorectomy, last menstrual period in menopausal women 6-12 months ago, height, weight, Quetelet index, slimming courses, and in men, varicosis. Associations between carpal tunnel syndrome and the use of oral contraceptives, age at menopause, diabetes, thyroid dysfunction, rheumatism, typing, and pinch grasp could not be demonstrated. PMID- 2260543 TI - Perinatal risk factors for inflammatory bowel disease: a case-control study. AB - To examine perinatal risk factors for Crohn's disease and ulcerative colitis, the authors analyzed birth records for 257 known case participants delivered from 1924 through 1957 at the University Hospital in Uppsala County, Sweden, and compared them with records for 514 controls delivered at the hospital. The two groups were matched by date of birth, sex, and either maternal age or parity. Eleven study variables were abstracted from standard forms that recorded health events during the pregnancy and the delivery hospitalization. Participants were more likely than controls to have a recorded health event (odds ratio (OR) = 4.4; 95% confidence interval (CI) 3.0-6.4). In a multivariate model, this increased risk was evident for infectious (OR = 3.8; 95% CI 2.6-5.8) and noninfectious (OR = 3.5; 95% CI 2.0-6.3) events. Perinatal health events may have contributed to 40% of the inflammatory bowel disease cases in our study. Infants from families with low socioeconomic status had greater risk of inflammatory bowel disease than did infants from families with high socioeconomic status (OR = 3.0, 95% CI 1.5 6.1). Perinatal health events and low socioeconomic status independently increased the risk of inflammatory bowel disease. PMID- 2260544 TI - An epidemic of respiratory complaints exacerbated by mass psychogenic illness in a military recruit population. AB - The authors report an episode of mass psychogenic illness exacerbating respiratory symptoms in military recruits. The epidemic occurred over a 10- to 12 hour period in September 1988, in a group initially complaining of cough and pleuritic chest pain. More than 1,800 men were evacuated from their barracks because of a suspected toxic gaseous exposure. Approximately 1,000 recruits developed at least one new symptom, 375 were evacuated by ambulance to receive further medical evaluation, and at least eight were hospitalized. Air sample testing from the area was unremarkable, and there were few abnormal physical examination or laboratory findings. The epidemiologic investigation included a questionnaire administered 2 weeks after the epidemic to 1,000 of the recruits involved. A total of 55% of those who completed the questionnaire reported the onset of at least one new symptom after supper, with at least 25% reporting the new onset of cough, light-headedness, chest pain, shortness of breath, headache, sore throat, or dizziness. A total of 18% received further medical evaluation. The development of new symptoms and the receipt of further medical evaluation were associated with evidence of physical stress, mental stress, and awareness of rumors of odors, gases, and/or smoke. This epidemic was unique because of its size and its occurrence in an all-male population. PMID- 2260545 TI - Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding. AB - Coagulase-negative staphylococci are the most common cause of bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and the Children's Hospital, Boston, Massachusetts. In 1982, nosocomial bacteremia with coagulase-negative staphylococci occurred in 45 of 882 (5.1%) infants admitted to these units who survived and remained in intensive care for more than 48 hours and were therefore at risk. The overall cumulative incidence (attack rate) of nosocomial bacteremia rose dramatically with decreasing birth weight. The smallest infants, those with birth weights of less than 750 g, experienced an overall risk of nosocomial bacteremia 44.5 times that of infants with birth weights of greater than 2,000 g. A large part of the excess risk for small babies was attributable to their longer hospitalizations. However, after adjustment for length of stay, the smallest infants still suffered a daily rate of bacteremia (incidence density) 5.3 times that of the largest, indicating a considerable residual effect of birth weight on the daily risk of nosocomial coagulase negative staphylococcal bacteremia. The results were similar in the two nurseries. Thus, there is still a substantially increased intrinsic risk of nosocomial coagulase-negative staphylococcal bacteremia among infants with very low birth weights, even after adjustment for duration of hospitalization, and differences in birth weight can confound comparative studies. PMID- 2260546 TI - The Strong Heart Study. A study of cardiovascular disease in American Indians: design and methods. AB - Available data indicate that cardiovascular disease has become the leading cause of death in American Indians. However, limited information is available on cardiovascular disease incidence, prevalence, and risk factors in this population. Reported cardiovascular disease rates vary greatly among groups in different geographic areas. These rates have been obtained from studies of varying sizes and different methodologies. The Strong Heart Study, which uses standardized methodology, is designed to estimate cardiovascular disease mortality and morbidity rates and the prevalence of known and suspected cardiovascular disease risk factors in American Indians. The study population consists of 12 tribes in three geographic areas: an area near Phoenix, Arizona, the southwestern area of Oklahoma, and the Aberdeen area of North and South Dakota. The study includes three components. The first is a mortality survey to estimate cardiovascular disease mortality rates for 1984-1988 among tribal members aged 35-74 years, and the second is a morbidity survey to estimate incidence of both first and first or recurrent hospitalized myocardial infarction and stroke (cerebrovascular disease) among tribal members aged 45-74 years in 1984-1988, and the third is a clinical examination of 4,500 tribal members aged 45-74 years in order to estimate the prevalence of cardiovascular disease and its associations with risk factors. Family history, diet, alcohol and tobacco consumption, physical activity, degree of acculturation, and socioeconomic status are assessed in personal interviews. The physical examination includes measurements of body fat, body circumferences, and blood pressure, an examination of the heart and lungs, an evaluation of peripheral vascular disease, and a 12 lead electrocardiogram. Laboratory measurements include fasting and postload glucose, insulin, fasting lipids, apoproteins, fibrinogen, and glycated hemoglobin. Also measured are serum and urine creatinine and urinary albumin. DNA from lymphocytes is isolated and stored for future genetic studies. PMID- 2260547 TI - Accuracy of current, 4-year, and 28-year self-reported body weight in an elderly population. AB - Participants in the 1987-1989 recall of the Charleston Heart Study were asked to report their current weight and to recall their weight in 1984 and 1960. Reported weights were compared with weights measured in the respective time periods. Subjects included male and female blacks and whites between ages 62 and 100 years. Correlations between reported and measured weights over all subjects were 0.979 for current, 0.935 for 4-year, and 0.822 for 28-year recall. Subjects in the lowest body mass index quartile overestimated their weight, while subjects in the highest quartile underestimated their weight. This tendency increased as the elapsed time increased. Deviations between measured and reported weights increased as performance on cognitive tests declined. PMID- 2260548 TI - The validity of questionnaire reports of a history of acute otitis media. AB - A random sample of 2,512 children with an estimated date of birth between July 1, 1985 and June 30, 1986 was monitored to age 2 years, and infection data based on a questionnaire and medical records were compared to evaluate the validity of questionnaire reports of a history of acute otitis media. The cumulative incidence of acute otitis media up to age 2 years in the questionnaire data was lower than in the record data (47.8 vs. 71.0%, respectively), although the number of episodes per child per year, the incidence rate for recurrent episodes, was considerably higher in the questionnaire data (1.27 vs. 0.93). The amount of acute otitis media was distinctly higher among the children of the nonrespondent parents. Finally, a tendency of questionnaire-based data sampling to damp the associations between various risk factors and acute otitis media is displayed. The results identify possible drawbacks which must be considered when interpreting questionnaire-based assessments of acute otitis media in childhood. PMID- 2260549 TI - A problem in identifying risk factors for disease using surrogate exposure variables that are under genetic control. AB - The use of a surrogate exposure variable to represent a complex of genetic and/or nongenetic factors is commonplace in epidemiologic studies. The authors present an hypothetical example in which a surrogate exposure results from underlying unknown genetic and nongenetic factors, yet only the genetic component predisposes to disease. The results demonstrate how risk may be incorrectly attributed to the nongenetic component of exposure and suggest a possible explanation for the identification of a risk factor in one case-control study in one population, but not in another study of the same disease conducted in a different population. PMID- 2260550 TI - The effects of measurement errors on relative risk regressions. AB - This paper concerns the effects of random error in numerical measurements of risk factors (covariates) in relative risk regressions. When not dependent on outcome (nondifferential), such error usually attenuates relative risk estimates (shifts them toward one) and leads to spuriously narrow confidence intervals. The presence of measurement error also reduces precision of estimates and power of significance tests. However, significance levels obtained by using the approximate measurements are usually valid and as powerful as possible given the measurement error. The attenuation in risk estimate depends not only on the size (variance) of the measurement error, but also on its distributional form, on whether it is dependent on the true level of the risk factor (whether it is of "Berkson" type), on the variance and distributional form of true levels of the risk factor, on the functional form of the regression (exponential or linear), and on the confounding variables included in the model. Error in measuring confounding variables leads to loss of control of confounding, leaving residual bias. Uncomplicated techniques of correcting the effects of measurement error in simple models in which distributions are assumed normal are available in the statistical literature. For these corrections, information on measurement error variance is required. Some approaches appropriate for more general models have been proposed, but these appear to be insufficiently developed for routine application. PMID- 2260551 TI - Re: "National sources of vital status information: extent of coverage and possible selectivity in reporting". PMID- 2260552 TI - Re: "Mammographic parenchymal patterns in women receiving noncontraceptive estrogen treatment". PMID- 2260553 TI - Re: "Acquired immunodeficiency syndrome, sexually transmitted diseases, and epidemiology: past lessons, present knowledge, and future opportunities". PMID- 2260554 TI - Jeune syndrome associated with cystinuria: report of two sisters. AB - Jeune syndrome is generally lethal in the first months of life. Surviving patients develop progressive renal failure and hepatic fibrosis. We describe 2 sisters, aged 7 and 2 years, respectively, who had Jeune syndrome associated with cystinuria. To our knowledge, this is the first reported association of these 2 autosomal recessive disorders. PMID- 2260555 TI - Central nervous system malformations in the CHARGE association. AB - Of 144 patients with the CHARGE association (literature 136, new patients 8), 47 (33%) had either a postmortem examination (30) or computerized axial tomography scan (17) of the head. Twenty-six of 47 (55%) had definite central nervous system (CNS) malformations; arhinencephaly, with or without other defects (11), holoprosencephaly (2), holoprosencephaly with arhinencephaly (1), other forebrain defects (3), hindbrain defects (3), or other defects (6). The presence of CNS malformation was most strongly associated with choanal atresia. This review demonstrates a predominance of forebrain anomalies, particularly arhinencephaly and holoprosencephaly, which may provide a clue to the mechanism of abnormal morphogenesis involved in CHARGE association. PMID- 2260556 TI - Nonreciprocal and jumping translocations of 15q1----qter in Prader-Willi syndrome. AB - We analyzed 33 cases of Prader-Willi syndrome (PWS) (including 2 personal observations) with translocations of 15q1----qter onto the terminals of different, apparently whole chromosomes. In all but one of the 23 informative cases the translocations was de novo. Thirty of the patients were unbalanced and 27 had a 45-chromosome constitution compatible with a 3:1 segregation. One balanced and 2 unbalanced translocations were jumping ones. The possible existence of actual non-reciprocal translocations in man is indicated by the following considerations about these and other PWS-associated rearrangements: 1) The observed excess of de novo translocations; 2) the relatively frequent familial occurrence of reciprocal 15q translocations; 3) the concurrence in 3 terminal translocation cases of an idic (15); 4) the visualization of jumping terminal translocations as simple transpositions rather than as successive reciprocal exchanges; 5) the predominance of true isodicentrics in PWS patients with extra inv dup(15) chromosomes; and 6) the rarity of extra derivatives resulting in 15q proximal tertiary trisomy. Additional findings in the present series were normal parental age in the de novo 45-chromosome cases, an apparently random distribution of telomeric breakpoints, and the occurrence of different breakpoints within the 15q1 region. PMID- 2260557 TI - Cleft lip and palate in Aicardi syndrome. AB - Cleft lip and palate were described previously in two patients with Aicardi syndrome; this report presents a third similarly affected child. Thus, facial clefts may be an occasional manifestation of Aicardi syndrome. PMID- 2260558 TI - David Klein: an appreciation. PMID- 2260559 TI - Living history--autobiography: genetics and environment from a personal perspective. PMID- 2260560 TI - Clonal lines of aneuploid cells in Rothmund-Thomson syndrome. AB - We report on a 21-month-old white boy with the Rothmund-Thomson syndrome. The karyotype on fibroblasts from an area of skin with poikiloderma showed the 46,XY,17 + der(17),t(2;17)(q11;p13) pattern. Karyotype on fibroblasts from normal skin showed two different abnormal patterns: 47,XY, + 8 and 47,XY, + i(2q). His lymphocytes had a normal 46,XY pattern. These findings indicate in vitro abnormalities. They are explained by a degree of chromosomal instability. PMID- 2260561 TI - LEOPARD syndrome: death because of chronic respiratory insufficiency. AB - Most patients with LEOPARD syndrome (L--lentigines, E--electrocardiographic conduction defects, O--ocular hypertelorism, P--pulmonary stenosis, A- abnormalities of genitalia, R--retardation of growth, D--deafness) seem to lead a relatively normal life, cardiomyopathy being the cause of death in a few. We describe a 19-year-old woman with an extreme form of the syndrome requiring correction of her thoracic deformities and cardiac defects, succumbing ultimately to respiratory insufficiency. The respiratory insufficiency was secondary to her deformed thorax, with the congenital heart defect contributing to the development of pulmonary hypertension. The ventilatory status of LEOPARD syndrome patients may require careful assessment. PMID- 2260562 TI - Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up. AB - Neonatal hemochromatosis (NH), an uncommon and generally fatal disorder of infancy, is defined by hepatic disease of antenatal onset, generally manifest at birth, and by stainable iron in a tissue distribution like that seen in heritable adult-onset hemochromatosis (HH). It is not known if parents and sibs of infants with NH are at risk of iron storage disease in later life. We provide 30-year follow-up for iron overload of a family in which 6 of 9 children died in utero or early in the neonatal period. Four of the 6 came to autopsy, where severe liver disease was found; in 3 of the 4, autopsy material could be reviewed. These 3 children had NH. Studies 30 years later did not identify HH or other iron storage disease in the parents or surviving sibs. These findings suggest that first degree relatives of persons with NH are not necessarily at increased risk of iron storage disease in later life. PMID- 2260563 TI - Cerebral palsy in multiple births in Western Australia: genetic aspects. AB - A study of cerebral palsy in multiple births was undertaken to test genetic involvement and assess the impact of the special conditions of pregnancy and parturition in these cases. Complete ascertainment of cerebral palsy in multiple gestations that occurred in Western Australia between 1956 and 1985 was obtained from the Western Australian Cerebral Palsy Register. There were 74 twins and 5 triplets. Data on sex, birth order, motor handicap, outcome in co-twins and triplets, zygosity, and pedigree information was obtained from the Register, hospital records, and, where possible, by interview of the parent(s) of the propositi. There was a significantly higher (P = 0.0026) concordance rate in MZ than in DZ twin pairs. However, pedigree studies showed no other relatives with a motor handicap similar to that of the propositi. This is consistent with a multifactorial cause in at least some of the cases. The sex ratio of affected twins was found to be 2.1 compared to 1.3 for singletons and all 5 affected triplets were boys. The trend of increasing sex ratio with increasing plurality was significant at the 1% level. PMID- 2260564 TI - Widukind Lenz--an encomium. PMID- 2260565 TI - Living history--biography: nature and nurture. PMID- 2260566 TI - Pre- and postnatal diagnosis of trisomy 4 mosaicism. AB - A liveborn girl with 46,XX/47,XX+4 mosaicism is reported for the first time. The diagnosis of true mosaicism was established initially in the assay of cultured amniotic fluid cells, although fetal blood obtained by percutaneous umbilical blood sampling showed a 46,XX chromosome constitution. The liveborn infant had manifestations previously reported in dup(4p) and dup(4q) syndromes. Cells in cord and arterial blood samples also were 46,XX, but cultures of placenta and bilateral forearm skin biopsies showed 46,XX/47,XX,+4 mosaicism. This case illustrates the disadvantage of chromosome analysis from blood alone when tissue specific mosaicism is present. PMID- 2260567 TI - Malformations and minor anomalies in children whose mothers had prenatal diagnosis: comparison between CVS and amniocentesis. AB - The frequency of abortion following chorionic villus sampling (CVS) is similar to that following amniocentesis. However, there is no information on long-term effects, such as malformations in liveborn children exposed to CVS. We evaluated 189 infants whose mothers had either CVS or amniocentesis as participants in the Canadian Collaborative Randomized Trial, a prospective assessment of the safety of CVS compared with amniocentesis. The participation rate of children who could be contacted was 95%. Ninety-five of the 189 infants (50.2%) had been exposed to CVS, 87 (46%) to amniocentesis, and 7 (3.8%) to both. (The latter group was excluded from calculations.) One hundred twenty-eight (128) children had greater than or equal to one minor anomalies but no major abnormalities: 58 of 95 (60%) in the CVS and 70 of 87 (80%) in the amniocentesis group. Twenty-six children had malformations: 17 (17.8%) in the CVS and 9 (10.3%) in the amniocentesis group. Only one anomaly, Sturge-Weber dysplasia (amniocentesis group), was potentially severe and none were life-threatening. Superficial cavernous hemangiomas (strawberry nevi) were noted more frequently in children in the CVS group (12.6%) than in the amniocentesis group (3.4%), but only slightly higher than in the general public. We conclude that exposure to CVS is not associated with an increased frequency of malformations or minor anomalies in infants compared with amniocentesis although we observed a higher frequency of superficial cavernous (strawberry) hemangiomas in the children in the CVS group. PMID- 2260568 TI - Agenesis or hypoplasia of major salivary and lacrimal glands. AB - We described a young man with almost total absence of the parotid glands, hypoplasia of both lacrimal glands, marked hypofunction of both submandibular glands, and left nasolacrimal duct atresia. Lack of tearing, severe dental caries, and conjunctival scarring following chronic xerophthalmia and conjunctivitis serve to alert pediatricians to this autosomal dominant disorder with considerable variation in expressivity. PMID- 2260569 TI - Acrofacial dysostosis with ambiguous genitalia. AB - We report on a 46,XY infant with mandibulofacial dysostosis, preaxial and postaxial limb anomalies, urethral stenosis with left hydronephrosis, and ambiguous genitalia with phallic/scrotal transposition. This infant with atypical pre/postaxial acrofacial dysostosis (AFD) is the first to be reported with ambiguous genitalia. The acrofacial dysostoses are a heterogenous group of disorders characterized by varying degrees of mandibulofacial dysostosis with acral limb defects and may represent a polytopic field defect. These disorders have generally been separated on the basis of their limb anomalies into preaxial, postaxial, lethal, and atypical types. Most cases are sporadic, but various causes have been postulated including autosomal dominant and recessive inheritance, a chromosome 2q duplication, and a possible case of diabetic embryopathy. We review the nonfacial/limb anomalies in other cases of AFD and compare them to those of our case, thereby expanding the spectrum of anomalies in these disorders. PMID- 2260570 TI - Tissue limited mosaicism in a patient with tetrasomy 9p. AB - Cytogenetic analysis of an abnormal newborn girl showed an extra chromosome with the characteristics of an isodicentric 9p chromosome [idic (9)(pter----q12--- pter)] in 98% of peripheral lymphocyte metaphases examined. This cytogenetic interpretation was substantiated by quantitative measurement of erythrocyte galactose-1-P-uridyltransferase (GALT) activity, which is consistent with the expression of 4 normal GALT genes. Cytogenetic results from skin fibroblasts showed mosaicism with only 11% of the metaphases having the extra chromosome. Selective genetic pressure based on a functional disadvantage of tetrasomy 9p in the skin is proposed. The in vivo establishment of cytogenetically normal cells in various tissues may be necessary for in utero survival of tetrasomy 9p infants. PMID- 2260571 TI - Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: review of brain, cardiac, and limb malformations. AB - Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q. PMID- 2260572 TI - Thymic-renal-anal-lung dysplasia in sibs: a new autosomal recessive error of early morphogenesis. AB - We report on 3 sisters with a syndrome of unilobed or absent thymus, renal and ureter agenesis/dysgenesis, and intrauterine growth retardation (IUGR). Two of the 3 infants had a unilobed lung and imperforate anus. Recurrence was detected prenatally by the presence of progressive oligohydramnios and IUGR, a unilateral echogenic cystic mass in the renal fossa, and low amniotic fluid disaccharidases in association with an imperforate anus. Several genetic mechanisms can be invoked to explain this occurrence including autosomal recessive inheritance and an unrecognized chromosome imbalance. PMID- 2260573 TI - Nonrandom chromosome changes in multiple sclerosis. AB - In order to study the role of genetic factors in multiple sclerosis, cytogenetic analysis was performed on 48 patients with the clinically defined disease. We found a high incidence of subjects (50%) with abnormal chromosomes, showing premature centromere division of the X chromosome and structural aberrations, translocations, or deletions that could suggest preferential breakpoints. Correlation between clinical and cytogenetic data showed that cytogenetic abnormalities were more common in patients with high frequency of relapse or with a progressive form of the disease. PMID- 2260574 TI - Homozygous achondroplasia: morphologic and biochemical study of cartilage. AB - We have performed histochemical, immunohistochemical, electron microscopic, and biochemical studies on the upper tibial cartilage from a case of homozygous achondroplasia. The growth zone was narrow and disorganized. Columnization was absent except for a few areas with short rows of cells. Hypertrophy was reduced to scattered clusters of cells. The provisional calcification was patchy and primary trabeculae were thick and irregularly arranged. Islands of fibrous or fibrocartilagineous tissue were found along the growth zone. The matrix did not stain with safranin O and lacked metachromasia, except for pericellular rims around the hypertrophic cell clusters. Staining with antibodies against the large proteoglycan monomers and chondroitin-4-sulfate was weakly positive. Electron microscopic examination showed that only a few cells had degenerative signs. In most areas of the matrix, proteoglycan granules were absent. Areas with dense collagen fibers were seen. In contrast to the growth zone, the cartilage of the remaining epiphyses had normal histochemical, immunohistochemical, and electron microscopic appearance. The large proteoglycan monomers had a normal composition and hydrodynamic size. Type II and XI collagen, pepsin fragments of type IX collagen, and several noncollagenous proteins extracted from cartilage had a normal electrophoretic migration. It is suggested that a mutation affecting a matrix component or a regulatory pathway present only or predominantly in the growth area of the chondroepiphysis might explain the findings. PMID- 2260575 TI - Ring chromosome 22 karyotype in a patient with Opitz (BBBG) syndrome. PMID- 2260576 TI - VACTERL and hydrocephalus. PMID- 2260577 TI - Sporadic occurrence of spondylocostal dysplasia and mesocardia in a Japanese girl. PMID- 2260578 TI - Parental origin of de novo translocation in a patient with both an inherited and a de novo chromosome translocation. PMID- 2260579 TI - Holoprosencephaly as a possible embryonic alcohol effect: another observation. PMID- 2260580 TI - Fragile X frequency. PMID- 2260581 TI - "Disorganization" gene in mutations. PMID- 2260582 TI - Etretinate embryotoxicity 7 months after discontinuation of treatment. PMID- 2260583 TI - OFDI syndrome. PMID- 2260584 TI - Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. AB - Cardiac rhabdomyoma, a rare benign tumor often detected in infancy, is frequently associated with tuberous sclerosis. This association is commonly stated to occur in 50% of all cases of cardiac rhabdomyoma. Recently at our institution, the prenatal detection of a cardiac rhabdomyoma in a fetus at no known risk for tuberous sclerosis emphasized the need to determine the frequency of association in order to provide accurate diagnosis and counseling in such situations. After a review of reported cases and review of patients from our institution diagnosed to have cardiac rhabdomyoma, we estimate that 51-86% of cardiac rhabdomyomas are associated with tuberous sclerosis. We present the results of our literature and case review. PMID- 2260585 TI - Baller-Gerold syndrome: an 11th case of craniosynostosis and radial aplasia. AB - We report on a patient with craniosynostosis, left radius aplasia, right radius hypoplasia, and other congenital anomalies. This is the 11th reported case of the Baller-Gerold syndrome. Autosomal recessive inheritance of this syndrome is suggested by evidence of probable parental consanguinity. PMID- 2260586 TI - "C" trigonocephaly syndrome: clinical variability and possibility of surgical treatment. AB - We report on 3 new cases of C trigonocephaly syndrome. In addition to the findings characteristic of this condition, one of the patients also had a large omphalocele. This patient was referred from a suburban hospital with a diagnosis of Down syndrome, stressing the fact that C syndrome is still under-recognized and underdiagnosed. Another patient was diagnosed at birth and immediately submitted to craniosynostectomy. A second operation was performed 7 months later resulting in normal brain growth and close to normal psychomotor development at 3 years, in contrast to the third patient, who was not treated surgically and was severely retarded at 4 years. PMID- 2260587 TI - C syndrome with apparently normal development. AB - C syndrome is an autosomal recessive craniosynostosis syndrome with characteristic cranial, facial, palate, and joint abnormalities. All but 2 of the reported patients have had severe mental retardation. We report on an 8-month-old girl with C syndrome and apparently normal development except for tasks hindered by her lower body abnormalities. We also offer a possible explanation for the palatal configuration. PMID- 2260588 TI - "C" trigonocephaly syndrome: two additional cases. PMID- 2260589 TI - Phenotypic overlap of Ehlers-Danlos syndrome types IV and VIII. AB - An 18-year-old Caucasian woman has been followed since age 12 years for Ehlers Danlos syndrome (EDS) with easy bruisability and "cigarette paper scars." Her chief complaint at age 17 years was tooth mobility, especially in the anterior mandible, necessitating the removal of the four incisors. Initial biochemical analysis of cultured skin fibroblasts indicated the presence of pepsin-sensitive type III collagen. Subsequent analysis of cultured skin fibroblasts by the same laboratory and another laboratory found no abnormality in the type III collagen with or without protease treatment. This is in distinction to the finding of abnormal type III collagen in the only two reported patients with EDS and early onset periodontitis who have had collagen analyses. One of them was diagnosed as EDS type IV and the other as EDS type VIII, although the defects of type III collagen were consistent with EDS type IV. The defect in type III collagen in some patients with early periodontitis and the considerable overlap of the clinical manifestations of EDS types IV and VIII point out the need for further studies of collagen formation and maturation in any patient who has early periodontitis and who has been classified with EDS type IV or VIII. PMID- 2260590 TI - A child with multiple congenital anomalies and karyotype 46,XY,del(14)(q31q32.3): further delineation of chromosome 14 interstitial deletion syndrome. AB - We report on an infant with a multiple congenital anomaly syndrome and severe developmental delay in association with a previously undescribed de novo interstitial deletion of chromosome 14 [karyotype: 46,XY,del(14) (q31q32.3)]. Comparison of the presented patient with previously reported cases of interstitial and terminal chromosome 14q deletions provides a group of patients monosomic for various overlapping portions of the distal half of chromosome 14q and suggests a limited similarity in phenotype among patients with common deleted 14q segments. All patients with distal 14q deletions were developmentally delayed, most were microcephalic and failed to thrive. Most of the patient's anomalies were limited to the face and head. Few major internal congenital anomalies were observed. These comparisons serve to further clarify possible associations of subchromosomal aberrations with specific phenotypes. PMID- 2260591 TI - Terminal deletion 6p23: a case report. AB - We report on a girl with cleft lip and cleft palate, antimongoloid slant of the palpebral fissures, umbilical hernia, skeletal anomalies, partial syndactyly, hypertonia with increased deep tendon reflexes, psychomotor and growth retardation, and other congenital anomalies. Cytogenetic studies demonstrated a 46,XX,del(6)(qter----p23:) chromosome constitution. PMID- 2260592 TI - Aminopterin-like syndrome sine aminopterin associated with translocation involving chromosomes 5 and 10. AB - We studied a baby born with physical features suggestive of the aminopterin syndrome, but without exposure of the mother to aminopterin during pregnancy. G banded chromosomes from peripheral blood lymphocytes had a normal 46,XX pattern. However, in 50 skin fibroblasts there was a normal female karyotype in 5 cells and 45 cells showed an apparently balanced reciprocal translocation involving the long arm of chromosome 5 (band q35) and the long arm of chromosome 10 (band q22). The relation of this mosaicism to the abnormal phenotype is unclear. PMID- 2260593 TI - Dermatoglyphics in the identification of women either with or at risk for breast cancer. AB - Fingerprints and palm prints were studied in 78 breast cancer patients, 391 patients at increased risk for developing breast cancer, and 64 control patients for the purpose of finding a pattern that would identify those women with breast cancer or those who are predisposed to its development. A pattern of 6 or more digital whorls was identified more frequently in women with breast cancer than in those without the disease (P less than 0.01). This finding was independent of known risk factors for breast cancer and was present in 28% of the cancer patients. No correlation was noticed between palm prints and breast cancer. The positive predictive value of 6 or more digital whorls was comparable to that of mammography and that of breast biopsy. With increasing age there was an increase in the positive predictive value associated with 6 or more digital whorls. It is concluded that digital dermatoglyphics may have a future role in identifying women either with or at increased risk for breast cancer such that either risk reduction measures or earlier therapy may be instituted. PMID- 2260594 TI - Progressive neurologic deterioration in a nine-year-old white male. PMID- 2260595 TI - Deletion of 16q with prolonged survival and unusual radiographic manifestations. AB - Deletion of 16q is characterized by mental retardation, microcephaly, a characteristic combination of minor facial anomalies, and broad halluces. Various break points have been described. This patient's phenotype is typical of this syndrome, but in addition, unusual radiographic findings were present. This chromosome abnormality is compatible with survival into adulthood. Expression of this phenotype does not appear to be correlated with specific break points. PMID- 2260596 TI - Follow-up of 16q deletions. PMID- 2260597 TI - Persistent hyperinsulinemic hypoglycemia of infancy ("nesidioblastosis"): autosomal recessive inheritance in 7 pedigrees. AB - Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) is a rare disease characterized clinically by persistent hypoglycemia with inappropriately elevated circulating insulin concentrations. Here we report on 7 pedigrees including 21 cases. The pedigrees are derived from 3 distinct ethnic groups, and include a very large Bedouin family, and Arab family, and 5 smaller pedigrees of Jewish families all of Eastern European origin. Data obtained from these families and from other families reported in the literature strongly suggest that PHHI is inherited as an autosomal recessive disorder. PMID- 2260598 TI - Concurrence of Robinow syndrome and Crigler-Najar syndrome in two offspring of first cousins. AB - Robinow syndrome and Crigler-Najar syndrome were encountered in 2 Saudi offspring of first cousins. Both died at age 4 months. The parents lost 2 previous children at age 2 months with progressive jaundice but without fetal facial characteristics. PMID- 2260599 TI - Congenital heart disease and Robinow syndrome: coincidence or an additional component of the syndrome? AB - We report on a girl with Robinow syndrome and pulmonary atresia with ventricular septal defect (VSD). Seven cases of Robinow syndrome with congenital heart defect (CHD) have now been described, 5 of whom had stenosis or atresia of the pulmonic valve. This suggests that CHD, especially right ventricular outlow obstruction, may be a component manifestation of this syndrome in some cases. Since early recognition of this type of heart lesion can minimize morbidity by facilitating optimal surgical therapy, thorough cardiac evaluation of all patients with Robinow syndrome seems warranted. PMID- 2260600 TI - Satisfaction with genetic counseling: dimensions and measurement. AB - Patient satisfaction has become a significant issue in evaluating medical care, although it has been largely neglected in genetic counseling. A 32-item questionnaire was designed to examine patient satisfaction and was administered to 76 clients in a genetic counseling center, and 56 parents attending a pediatric outpatient clinic (the control group). Factor analysis showed 3 dimensions to satisfaction with genetic counseling: instrumental, affective, and procedural. The general level of satisfaction was found to be lower in the genetic counseling group than in the control group. This finding was interpreted as expressing basic properties of genetic counseling. The most important determinant of satisfaction in both groups was satisfaction with the content of information provided in counseling. Some affective and procedural aspects of genetic counseling were found more satisfying, and more important in determining genetic clients' general sense of satisfaction, as compared to the control subjects. PMID- 2260601 TI - Conjoined twins discordant for cleft lip and palate. AB - Female thoraco-omphalopagus twins were of equal size and had similar abnormalities related to the twinning site. However, one twin was more severely affected and also had cleft lip and palate which the co-twin did not have. The implications of this are discussed. PMID- 2260602 TI - Tetralogy of Fallot in three sibs. AB - We report on three sibs (2 boys, one girl) with tetralogy of Fallot from non consanguineous parents. The first child died during corrective surgery in 1972 from irreversible right ventricular failure. Corrective surgery was successful in the 2nd son and the daughter. The occurrence of tetralogy of Fallot in 3 sibs suggests a recessive gene. PMID- 2260603 TI - Application of a flowchart for the detection of lysosomal storage diseases in 105 high-risk Brazilian patients. AB - Lysosomal storage diseases (LSD) are a group of more than 40 disorders, many of them with overlapping phenotype, in which clinical diagnosis is often difficult. Definitive diagnosis is based on enzyme assays, a large number of such assays usually being necessary during the investigation of each patient. In addition, there will frequently be a need for tissue culture in order to provide enough material for analysis. Taking into account these difficulties, we designed a flowchart for the detection of LSD that is based on 2 sets of tests requiring only random urine and heparinized blood. Here we describe this routine and report the results of its application to 105 Brazilian patients in whom a LSD was suspected. We think that the application of this rationale represents a saving of work and costs, and should be of special interest to genetic centers in developing countries. PMID- 2260604 TI - New study on the relationship between oral clefts and fetal loss. AB - The sibships of 741 non-syndromic individuals with cleft lip with or without cleft palate (CL +/- P), those of 115 subjects with isolated cleft palate (CP), plus 2 series of controls of the same size were studied in a variety of ways. The 2 most significant findings were a) a higher fetal loss in the sibships of probands of the most frequently affected sex (CL +/- P: male; CP: female) and b) increased fetal mortality in the sibships with sporadic cases of CL +/- P when compared to that found in sibships with more than one affected. In general the results do not support the hypothesis of a causal relationship between fetal death and non-syndromic CL +/- P or CP. PMID- 2260605 TI - Monozygotic twins discordant for the Russell-Silver syndrome. AB - Russell-Silver syndrome is a disorder of unknown cause. A number of familial cases have suggested autosomal dominant inheritance. We report on monozygotic twins discordant for the Russell-Silver syndrome. Our findings suggest that the cause of Russell-Silver syndrome is not explained entirely by genetic factors. The possible role of the intrauterine environment as an etiologic component of Russell-Silver syndrome is discussed. PMID- 2260606 TI - Cohen syndrome and de novo reciprocal translocation t(5;7)(q33.1;p15.1). AB - Here we report on a de novo apparently balanced reciprocal 5q;7p translocation in a 15-year-old girl with apparent Cohen syndrome characterized by hypotonia, obesity, multiple congenital anomalies, and mental retardation. This case may indicate that the gene for Cohen syndrome is at 5q33.1 or 7p15.1. PMID- 2260607 TI - Euchromatic 16p+ heteromorphism: first report in North America. AB - A heteromorphism of the short arm of 16 (16p+) was discovered in 2 unrelated infants. By G banding, the euchromatic variant appears as a light and a medium dark band just distal to the centromere. This results in an increase of the short arm by about 1/3. The same variant was present in the normal father and the normal paternal grandmother in one family and mildly retarded mother in the 2nd family. The anomalies of the 2 infants are not similar and are apparently unrelated to the 16p+ variant. Though the discovery of such euchromatic variants is highly significant for clinical diagnosis, their genetic significance and mode of origin remain to be elucidated. PMID- 2260608 TI - Monochorionic diamniotic minimally conjoined twins: a case report. AB - We present the second case of monochorionic diamniotic (MC/DA) conjoined twins. There was minimal conjunction, which was predominantly extrafetal and confined to the periumbilical ventral region. The omphalopagus twins, attached to a single forked umbilical cord, were connected by a shared umbilical hernia containing the ileum of twin B. The only visceral conjunction, located just within the belly of twin A, was midileal with the 2 separate ileums converging toward a short segment of shared muscularis propria and of side-to-side fistulization. Gastrointestinal and musculoskeletal anomalies were present in both twins with severe amyoplasia and arthrogryposis multiplex in twin A. Possible mechanisms underlying this unusual form of MZ twinning are discussed. PMID- 2260609 TI - ADAM sequence and innocent amniotic band: manifestations of early amnion rupture. AB - Thirteen placentas with early amnion rupture (EAR) are described. These placentas were characterized by the absence of amniotic epithelium on the fetal surface, presence of a slightly fibrotic small amniotic band (remnant) attaching to the umbilical cord at the placental end, and the presence of degenerated vernix squamous cells in the fibrous stroma of chorion and amnion. Eight fetuses had ADAM sequence. Six of these fetuses were miscarried between 16 and 28 weeks of gestation. Two affected infants were born alive at gestational ages of 29 and 39 weeks. Five infants were spared by ADAM sequence; two had the umbilical cord strangulated by an amniotic band and were delivered at 27 and 37 weeks. In the 3 infants unassociated with ADAM sequence or strangulation of the umbilical cord, their placentas were interpreted as having innocent amniotic band (IAB) and they were delivered between 32 and 40 weeks. The findings in this study support Torpin's hypothesis that ADAM sequence is a complication of EAR. This ADAM sequence due to simple EAR must be separated from the limb body wall malformation complex because visceral anomalies are uncommon in the former condition but are frequently seen in the latter. In this study the placental pathology of EAR was helpful in confirming the ADAM sequence in the fetus. PMID- 2260610 TI - Roberts syndrome or "X-linked amelia"? AB - We report on a syndrome of tetra-amelia, facial clefts, absence of ears, nose, and atresia ani, affecting 7 male infants or fetuses in one Arab Moslem kindred. The combination of anomalies described in each affected member is consistent with Roberts syndrome and the prevalence of intermarriage in this kindred could suggest an autosomal recessive mode of inheritance. Alternatively, the existence of a new syndrome, namely, "X-linked amelia" is proposed. PMID- 2260611 TI - The syndrome of Mobius sequence, peripheral neuropathy, and hypogonadotropic hypogonadism. AB - We report on a 17-year-old Japanese boy with Mobius sequence, peripheral neuropathy, and hypogonadotropic hypogonadism, the fourth such case known to us. The association of peripheral neuropathy and hypogonadotropic hypogonadism in Mobius sequence seems to be more than coincidence. Pulsatile gonadotropin releasing hormone administration for 3 months showed the effectiveness of this treatment for this patient. PMID- 2260612 TI - Piebaldism, an autosomal dominant trait distinct from Waardenburg syndrome. PMID- 2260613 TI - Recombinant human erythropoietin: physiology, pathophysiology of anemia in renal failure, and economic aspects related to dosing. AB - The anemia associated with renal failure has been studied for over 150 years. It results primarily from inadequate production of erythropoietin such that plasma levels in dialysis patients are only 25% of those expected for the degree of anemia. Shortened red call survival, iron and other nutritional deficiencies, and uremic inhibitors have a secondary and minor role. Recombinant human erythropoietin (rHuEPO) is now used to treat this anemia. It is heavily sialated, which permits its circulation long enough to act on the bone marrow where, in concert with other growth factors, it commits progenitor cells to the erythroid cell pathway. Major issues related to clinical use of rHuEPO are dosage, resistance, and cost. Pharmacokinetic studies predict significant weekly dose reductions (and therefore cost savings) using the subcutaneous route compared to the intravenous route permitting more patients to be treated optimally. Biological heterogeneity and not hyperparathyroidism or aluminum overload accounts for most instances in which more than 450 U/kg/wk of rHuEPO is required. PMID- 2260614 TI - The practical aspects of therapy with rHuEPO. AB - A number of multicenter US trials provide extensive experience with the benefits of recombinant human erythropoietin. The dose-response relationships obtained using epoetin-beta are presented. Recommendations with respect to optimal dose requirements as derived from these trials are reviewed. How low-dose therapy affects hematocrit as well as its ability to decrease transfusion requirements is discussed. Low-dose therapy is also examined in the context of a possible decrease in adverse experiences. Dosing regimens, including once weekly vs. three times weekly i.v. therapy, is explored. Preliminary information on the efficacy of subcutaneous injections is discussed in light of the pharmacokinetic data currently available. The importance of adequate iron stores is emphasized at all doses. Regardless of the route of administration, the level of iron stores is critical. PMID- 2260615 TI - Clinical and blood rheologic stability in erythropoietin-treated predialysis patients. AB - We assessed human recombinant erythropoietin (rHuEPO) as treatment for anemia in azotemic patients who did not require dialytic therapy. The study group consisted of 5 azotemic men and 5 women (mean serum creatinine concentration 5.2 +/- 3.2 mg/dl) whose mean hematocrit was 27.4 + 3.0%. Of these, 5 subjects had diabetic nephropathy. The study was a 12-month rHuEPO maintenance (open label) trial in which a previously established median i.v. dose of 50 U/kg was given three times each week. The rHuEPO was temporarily discontinued when the target hematocrit of 37% was achieved, and after the hematocrit decreased below 35%, it was restarted at half the initial dose. Of the 10 subjects who started the trial, 2 (both nondiabetic) deteriorated early in the study, and before a hematocrit rise was attained commenced maintenance hemodialysis. All subjects completed the year of study and achieved the target hematocrit. Mean hematocrit rose 42% (p less than 0.001) in a mean period of 3.3 +/- 1.3 months. When treatment was interrupted at a hematocrit of 37%, mean absolute reticulocyte count fell from 1.21 +/- 0.59% to 0.38 +/- 0.14% within one week. After rHuEPO was withdrawn, the increase in hematocrit persisted for a mean of 13.0 +/- 6.0 days and patients were able to sustain hematocrits above 35% for a mean of 1.44 +/- 0.6 months. Coincidentally with the rise in hematocrit during rHuEPO treatment, whole-blood viscosity increased significantly (p less than 0.001) but remained within the range for individuals with normal renal function at an equivalent hematocrit (p greater than or equal to 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260616 TI - Resistance to recombinant human erythropoietin in hemodialysis patients. AB - The administration of recombinant human erythropoietin (rHuEPO) to anemic hemodialysis patients is usually followed by a rapid increase in hemoglobin. Initial 'nonresponders' may either respond to higher doses of rHuEPO or rarely may remain totally unresponsive. Schematically, one can distinguish between a state of relative and absolute resistance to the action of the hormone. The most common causes of resistance are iron deficiency, aluminium overload, episodes of infection or other inflammatory processes, probably severe hyperparathyroidism, acute or chronic hemolytic conditions, acute or chronic blood loss, folate deficiency, and hemoglobinopathies in exceptional instances. Antibody formation against rHuEPO or marrow fibrosis secondary to rHuEPO treatment can be discarded as potential causes of resistance. PMID- 2260617 TI - The treatment of anemia with low-dose recombinant human erythropoietin. AB - Recombinant human erythropoietin is effective therapy for the anemia of chronic renal failure. Hypertension, seizures, dialysis access thromboses, and clotted dialyzers have been reported as problems associated with the use of this drug. To test the hypothesis that low-dose erythropoietin is effective and safe, we gave 37 chronic hemodialysis patients this compound (3,000 units, i.v.) three times each week for 3 months. Before and for 3 months during therapy, we measured hemoglobin, hematocrit, blood transfusions, blood pressure, access thromboses, seizures, and clotted dialyzers. After 2 months of treatment, mean hemoglobin concentration and mean hematocrit increased significantly. Five patients had no increase in either value. In 4 of these 5 nonresponders, blood loss accounted for treatment failure. Neither blood pressure nor the incidence of access thromboses, seizures, and clotted dialyzers changed during the 3 months of therapy. We conclude that recombinant human erythropoietin is effective as treatment for the anemia of chronic renal failure at much lower doses than have been reported previously. The low incidence of adverse events may be related to the low dose used. PMID- 2260618 TI - Implications of recombinant erythropoietin therapy for renal transplantation. AB - We previously reported on the efficiency by which endogenous erythropoietin production corrects anemia after successful renal transplantation. Recent clinical experience with recombinant human erythropoietin in renal failure has demonstrated major benefit in correcting anemia with few adverse consequences. This article reviews our experience to date with recombinant human erythropoietin use in transplant recipients and explores the impact of therapy for the dialysis population awaiting transplantation. The issues of ongoing need for pretransplant blood transfusion, presensitization, organ transplant demand, therapeutic use of human recombinant erythropoietin for chronic rejection, and impact of an expanding, high-quality transplant recipient pool are discussed in the context of the recombinant erythropoietin era. PMID- 2260619 TI - Practical approach to initiation of recombinant human erythropoietin therapy and prevention and management of adverse effects. AB - Therapy with recombinant human erythropoietin (rHuEPO) can reverse anemia and improve the quality of life in anemic hemodialysis patients. However, therapy is costly and must be used efficiently. An initial rHuEPO dose less than 50 U/kg intravenously three times weekly may be adequate to achieve a hematocrit of 30 33% in many patients. Acquired iron deficiency is a common problem during rHuEPO therapy and must be prevented with oral and parenteral iron replacement to maintain the efficacy of rHuEPO. Patients should be monitored carefully for additional problems including: an increase in blood pressure; onset of seizures or headaches; increased blood potassium, phosphate, and creatinine concentrations; enhanced coagulability resulting in dialyzer and vascular access clotting; and myalgias with a 'flu-like' syndrome. PMID- 2260620 TI - Warner-Lambert/Parke-Davis Award lecture. Pathobiology of the intestinal epithelial barrier. AB - The major route of passive permeation across intestinal epithelia is paracellular. The intercellular tight junction lies in and serves as the rate limiting barrier in this paracellular pathway. Once viewed as static, it is now clear that the structure and permeability of the tight junction is highly dynamic. Not only may inflammatory events (cytokines, neutrophil transmigration) reversibly effect the tight junction but this key barrier also is regulated by physiologic events such as activation of absorptive cell Na(+)-nutrient cotransporters. Such physiologic regulation of the junction is of major importance to the absorption of nutrients via parcellular solvent drag. PMID- 2260621 TI - Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma. AB - Transcripts for the muscle regulatory gene MyoD1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft-tissue sarcomas. Here we report the distribution of MyoD1 protein, determined by reactivity with anti-MyoD1 polyclonal sera in normal tissues, rhabdomyosarcoma cell lines, and in a variety of pediatric solid tumors. The distribution of MyoD1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle. All six human rhabdomyosarcoma cell lines analyzed expressed MyoD1 mRNA transcripts as well as immunoreactive protein. The immunohistochemical expression of MyoD1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors. Each of 16 rhabdomyosarcoma specimens was positive for MyoD1, including four that did not express the intermediate filament protein desmin. Two of five specimens originally designated sarcoma type indeterminate (STI) and two of three specimens originally designated extraosseous Ewing's sarcoma (EOE) were positive for MyoD1, suggesting commitment to myogenic differentiation. Three of eight Wilms' tumors, which also expressed desmin and had clearly evident myogenic elements, also were positive for MyoD1. Tumors that failed to express MyoD1 protein included neuroblastoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma, embryonal sarcoma of the liver, malignant fibrous histiocytoma, malignant rhabdoid tumor, and Ewing's sarcoma of the bone. These results indicate that expression of MyoD1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma. Furthermore MyoD1 staining may be a valuable adjunct in the classification of pediatric soft-tissue sarcomas. PMID- 2260622 TI - Irreversible tubulointerstitial damage associated with chronic aminonucleoside nephrosis. Amelioration by angiotensin I converting enzyme inhibition. AB - Chronic aminonucleoside nephrosis is variably associated with tubulointerstitial damage, depending on the route and frequency of drug administration. Recently, different groups have shown this injurious tubulointerstitial process to be reversible, coinciding with the resolution of heavy proteinuria to normal values. The authors have previously shown that a single jugular intravenous administration of puromycin aminonucleoside (PA) to male Munich-Wistar rats produces a triphasic pattern of glomerular injury and proteinuria, which culminates in focal glomerulosclerosis 70 weeks after drug administration. The authors now report the later progression of the tubulointerstitial morphologic abnormalities associated with acute nephrosis (phase I), despite spontaneous resolution of glomerular injury during the intermediate period (phase II) in this model. Although treatment of rats with the angiotensin I converting enzyme inhibitor enalapril (50 mg/l drinking water) over the 70-week period did not affect the magnitude of proteinuria during the acute nephrotic phase, enalapril prevented the recurrence of proteinuria (phase III), as well as significantly reducing the severity of interstitial fibrosis, extent of tubular dilatation, and number of intratubular casts on semiquantitative scoring at the conclusion of the study. In addition, enalapril-treated rats had less low-molecular-weight protein excretion during the recurrent phase of proteinuria, suggesting a preservation of tubular functional capacity to reabsorb these proteins. In vitro cytotoxicity studies showed only the glomerular visceral epithelial cell to be sensitive to PA, in contrast with rat tubular epithelium and other cellular controls. Although the exact pathogenetic mechanism responsible for the development of the tubulointerstitial damage remains unknown, PA in vitro does not adversely affect rat tubular epithelium; there is however a clear correlation between the magnitude of recurrent proteinuria and the severity of tubulointerstitial morphologic abnormalities, as suggested by the beneficial effect of converting enzyme inhibition on both of these untoward processes. PMID- 2260623 TI - Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. AB - The reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks, followed by bilioduodenal anastomosis for 3 weeks. Bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5' nucleotidase, alkaline phosphatase, and bilirubin during the first 3 days. Then these levels decreased to threefold, twofold, and 100-fold the normal values, respectively, during the following 4 weeks. Histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis, with only slight inflammation and necrosis. The distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation, using the indirect immunoperoxidase method. Fibrous septa were found to be strongly stained for collagens I, pro-III, III and IV, fibronectin, and laminin. The most intense staining was found in enlarged periportal areas, collagen IV and laminin being particularly abundant around newly formed bile ducts. These changes paralleled high steady-state levels of alpha 1(I) and alpha 1(IV) collagen and B2 chain laminin mRNAs. Relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5' nucleotidase, alkaline phosphatase, and bilirubin toward normal values. A dramatic resorption of bile duct proliferations and periportal fibrosis were observed. Three weeks after bile duct repermeabilization, immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal, except for collagen IV, which remained abundant in the sinusoids when compared with the normal liver. In parallel, the steady-state B2 chain laminin mRNA level became lower than in cholestatic livers, whereas alpha 1(I) and alpha 1(IV) mRNAs were almost undetectable. These results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction, suggesting that an active degradation of matrix protein occurs, except for collagen IV in the sinusoid. PMID- 2260624 TI - Ultrastructural organization of contractile proteins in rat glomerular mesangial cells. AB - Glomerular mesangial cells of the rat kidney contain actin, nonmuscle myosin, tropomyosin, and the muscular Z-line protein, alpha-actinin. This was shown for actin, myosin, and alpha-actinin by immunoblotting as well as by immunoelectron microscopy. Tropomyosin was localized in mesangial cells by immunofluorescence. In cultured mesangial cells, actin, myosin, and alpha-actinin constitute a considerable amount of the total cellular protein contents. In mesangial cells in situ actin, myosin and alpha-actinin were found to be colocalized within conspicuous microfilament bundles that traverse the cell body or major processes in various directions and project into either the tonguelike pericapillary processes, which run toward mesangial angles, or into the microvilluslike lateral extensions that abut on the perimesangial portion of the glomerular basement membrane (GBM). Thereby, the GBM of opposing mesangial angles as well as of opposing portions of the perimesangial GBM are regularly interconnected by filament bundles within mesangial cells that contain actin, myosin, and alpha actinin. The authors suggest that the major function of actin-, myosin-, and alpha-actinin-containing filament bundles in mesangial cells is to create an isometric tension (or minute isotonic contractions) to counteract the distending forces of the rather high intracapillary hydraulic pressure and its resulting pressure gradients across the capillary wall and across the perimesangial GBM. PMID- 2260625 TI - Capillary leakage in inflammation. A study by vascular labeling. AB - The local injection of pure inflammatory mediators induces venular leakage. To test the effect of endogenous mediators from dying tissue on vascular leakage, the authors devised an experimental model simulating an infarct, whereby living vessels would be exposed to fragments of organs undergoing aseptic necrosis. Tissues from donor rats were implanted aseptically in the cremasteric sac. Control rats were implanted with materials deemed to be as close as possible to nonirritating: boiled tissues and spheres of Teflon or glass. At different points the rats were injected intravenously with carbon black and killed an hour later. Whole cremaster mounts showed that vascular labeling was strictly venular up to 8 hours, mixed with capillary labeling between 12 and 24 hours, and mainly or exclusively capillary at 48 hours. Histology showed an acute inflammatory infiltrate in the labeled areas. A similar but weaker labeling pattern accompanied by milder inflammation was seen in controls. These results indicate that the vascular leakage in aseptic inflammation is biphasic, first venular, then capillary; and that the capillary phase is induced by the inflammatory reaction itself, possibly through a form of diffuse angiogenesis. PMID- 2260626 TI - HIV-associated myocarditis. Pathology and immunopathology. AB - Autopsy studies of AIDS (acquired immune deficiency syndrome) patients showed a high incidence of myocarditis. To attain a better understanding of the pathogenesis, the pathology and immunopathology of nine endomyocardial biopsies with active myocarditis from 18 human immunodeficiency virus (HIV)-positive patients were systematically characterized. These were compared with 17 biopsies with active myocarditis from patients without AIDS risk factors. In both groups, the myocarditis consisted of either multifocal or interstitial infiltrates of small lymphocytes and isolated myocyte necrosis. The lymphocytes consisted of T cells (CD2+, CD3+) and cells not identified by the usual markers. B cells, monocytes, CD4+ cells, and natural killer (NK) cells were only rarely observed. All of the HIV-positive patients but only 7 of 17 non-HIV patients had CD8+ lymphocytes in the infiltrates (P less than 0.01). The arteriolar endothelium demonstrated induced class I (HLA-A, B, C) and II (HLA-DR) antigens in both groups. In situ hybridization for HIV-1 failed to identify the virus in the specimens. The immunopathology is consistent with a cell-mediated injury to the myocytes in HIV-positive patients and is similar to a subgroup of myocarditis in the non-HIV group. PMID- 2260627 TI - In vivo defibrination results in markedly decreased amounts of fibrinogen in rat megakaryocytes and platelets. AB - Recently evidence was provided for a pathway whereby circulating fibrinogen enters megakaryocyte granules by an endocytic mechanism. Synthesis of fibrinogen by megakaryocytes has been reported. To determine the relationship between plasma fibrinogen and alpha-granule fibrinogen in megakaryocytes and platelets, the fibrinogen content of these cells was studied in rats defibrinated by use of Ancrod, a thrombinlike enzyme purified from the venom of Agkistrodon rhodostoma. Unlike thrombin, Ancrod does not induce platelet secretion. Rats were injected with Ancrod (50 units/kilogram body weight) at 8-hour intervals for 5 days. There were no significant changes in platelet counts. Blood from the treated rats failed to clot, and plasma fibrinogen levels were less than 15 mg/dl. Bone marrow from defibrinated rats and untreated control rats was stained immunohistochemically for fibrinogen and two other alpha-granule proteins, albumin and platelet factor 4 (PF4), in plastic-embedded sections. The presence of these three proteins in platelets was detected by Western blots. Only trace amounts of fibrinogen were detected in megakaryocytes and platelets from defibrinated rats, but fibrinogen in control megakaryocytes and platelets was readily demonstrated. However defibrinated and control rats did not differ in albumin and PF4 content in megakaryocytes and platelets. It is concluded that a major portion of rat platelet fibrinogen is derived from plasma by endocytosis by megakaryocytes. PMID- 2260628 TI - Intimal proliferation in an organ culture of human saphenous vein. AB - This study investigated whether intimal proliferation, the characteristic feature of the response of human saphenous vein to arterial implantation, also occurs in organ culture. Vein segments were maintained for 14 days in medium supplemented with 30% fetal bovine serum. Tissue viability (measured by adenosine triphosphate [ATP] concentration) decreased only 20% from 280 +/- 20 to 220 +/- 20 nmol/g wet weight. In veins prepared for culturing, endothelial loss (approximately 20%) was confined to near the cut edges. Cultured veins retained an endothelial layer in the initially undamaged areas, while the initially injured areas became covered by a mixture of endothelial and vascular smooth muscle cells. Autoradiography in conjunction with scanning electron microscopy showed the presence of proliferating cells on the intimal surface. Transverse sections of cultured veins showed the development of a new intima containing vascular smooth muscle cells identified by immunocytochemistry with anti-alpha-actin. There were also endothelial cells identified with Ulex europaeus lectin arranged in capillarylike structures. Pulse or continuous labeling of cultures with [3H]thymidine showed that proliferating cells were confined to the new intima and suggested that the smooth muscle cells in this layer arose from both immigration and proliferation. The results demonstrate that intimal proliferation occurs in organ culture of human saphenous veins. PMID- 2260629 TI - Pathophysiologic effect of interleukin-1b in the rabbit retina. AB - Interleukin-1 is a potent immunomodulator and has been shown to initiate many aspects of the inflammatory response. To determine the effects of IL-1b in the central nervous system (CNS), the rabbit retina was used, adjacent to which factors can be injected with minimal trauma and both pathologic and physiologic effects can be monitored. Intravitreal injection of 300 units of IL-1b induced an alteration in the visual evoked potentials (VEP) that was associated with marked intravascular red blood cell accumulations, hemorrhage, and cellular inflammation of the epiretinal vessels. Analysis of these events showed slowing and occasional hyper-excitability of the compound action potential of the optic tract and of the cortical VEP that correlate with the maximum inflammatory response. Histologic studies show the following: no apparent response occurs within the first 1.5 hours after intraocular challenge; and between 3 and 6 hours after injection an extensive intravascular red blood cell accumulation and progressive hemorrhage is accompanied by an increase in the number of mononuclear (MN) cells and the appearance of polymorphonuclear (PMN) cells. Polymorphonuclear cells continue to increase with time to give a single wave of inflammation that peaks 24 hours after injection, while the number of MN cells steadily increases. These events are associated with changes in the permeability of the blood-brain barrier and correlate with the electrophysiologic dysfunctions. Forty-one hours after injection, MN inflammation, reactive gliosis, and residual PMN inflammation are evident. Neutralization with specific antibody inhibited the responses through 6 hours after injection. It is concluded that the rabbit retina provides a valuable model for the in vivo analysis of CNS inflammation. PMID- 2260630 TI - The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease. AB - The authors examined the hypothesis that senile plaques of Alzheimer's disease (AD) are formed by abnormal leakage of amyloidogenic precursors from brain capillaries by quantitative analysis of the spatial relationship between capillaries and amyloid plaques. Vibratome sections (40 mu) of the hippocampus, including the entorhinal cortex, obtained at autopsy from AD subjects, were immunostained with a monoclonal antibody to beta-protein and counterstained with rabbit serum to either the glucose transporter protein, a cerebral endothelial marker, or collagen type IV, a basal lamina marker. The authors found that while 60% to 77% of amyloid plaques were associated with capillaries, only 8% to 13% were penetrated by a capillary, the remainder being adjacent. To test whether 1) the area occupied by amyloid plaques or 2) the border zone (10-mu rim) surrounding amyloid plaques has a statistically higher density of capillaries than 3) the remaining gray matter, similarly double-stained 6-mu sections from five AD subjects were photographed and the capillary densities in the three areas calculated. Capillary density was significantly lower in 1) than in 3) and higher in 2) than in 3), while the combined area of 1) and 2) showed the same capillary density as 3). Similar results were obtained by using either the glucose transporter or the collagen type IV antibodies. Because capillary density is low within, and high in regions that immediately surround amyloid plaques, our findings suggest that amyloid plaques exclude capillaries or lead to their degeneration, or both. The latter possibility was investigated by triple-staining tissue sections with antibodies to beta-protein, glucose transporter, and collagen type IV. The proportion of glucose transporter-negative capillaries was not significantly different in areas inside or outside of the plaques. Thus, the authors found no evidence of basal lamina remnants consistent with capillary degeneration preferential to amyloid plaques. Although a small number of capillaries showed amyloid deposition just beneath the basement membrane, the authors conclude that capillaries play only a limited direct role, if any, in amyloid plaque formation, and that the apparent association of amyloid plaques and capillaries is no more than a chance contact. PMID- 2260631 TI - Discordant expression of antigens between intraepidermal and intradermal T cells in mycosis fungoides. AB - Using immunohistochemical methods, the authors studied the expression of pan-T- and majority-T-cell antigens (CD5, CD2, CD3, TCR-beta, CD7) and T-cell subset antigens (CD4, CD8) in cutaneous T cells in mycosis fungoides (MF) (177 biopsies from 124 patients) and a variety of inflammatory lesions (45 biopsies from 45 patients). The authors detected the absence of pan-T- or majority-T-cell antigens, or of both T-cell subset antigens, from T cells in the epidermis but not the dermis in 15 MF biopsies (8%) from 11 MF patients (9%), but in none of the inflammatory skin lesions. The opposite picture, characterized by lack of antigen expression by the dermal T cells only, was not seen in any of the MF or inflammatory lesions. The absence of antigen expression by epidermal but not dermal T cells, which the authors have termed antigen discordance, was most prevalent for CD5, CD7, and TCR-beta, each being discordant in 6% to 7% of MF cases or patients tested. Among the MF biopsies showing antigen discordance, 14 of 15 biospies (93%) from 10 of 11 patients (91%) were discordant for two or more antigens. Antigen discordance was not an artifact of treatment, because none of the patients showing discordance was receiving treatment at the time of their initial discordant biopsy. The discordance was the only immunophenotypic abnormality detected in 8 of 15 (53%) of the discordant MF biopsies. Thus, this antigen discordance was an important diagnostic feature that allowed the immunophenotypic distinction of MF from a variety of inflammatory skin lesions. PMID- 2260632 TI - Wound healing in the media of the normolipemic rabbit carotid artery injured by air drying or by balloon catheter de-endothelialization. AB - The response to air-dry injury to the carotid artery of the normolipemic rabbit was compared with the response to de-endothelialization with a balloon catheter. Air drying induced an inflammatory response that resembled arteritis rather than atherosclerosis. There was medial damage, neutrophil but not macrophage infiltration, and fibrin formation, limited smooth muscle proliferation, which regressed after 3 months, and no lipid deposition. Within 1 week the smooth muscle cells were mainly of the secretory phenotype, and a neointima had formed. At 4 weeks the neointimal proliferation continued, but most cells showed a contractile phenotype. By 3 months, the lesion consisted of fibromuscular thickening with few small smooth muscle cells. Balloon injury induced minimal medial damage and continuing intimal proliferation with no evidence of regression by 3 months. It is concluded that air drying the carotid artery induces smooth muscle damage as well as endothelial cell loss, and this stimulates a wound healing mechanism that is different from the response to selective intimal injury. PMID- 2260633 TI - The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection. AB - The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination. PMID- 2260634 TI - Distribution of endogenous albumin in the glomerular wall of proteinuric patients. AB - Glomerular proteinuria seems to be related, in part, to loss or impairment of the normal barrier function of the glomerular capillary wall. To investigate the functional properties of this barrier, endogenous albumin was revealed in the glomerular wall of proteinuric patients and compared with a nonproteinuric control by immunoelectron microscopy using the protein A-gold method. In the control biopsy, peaks of albumin accumulation were noted in the subendothelial area and in the inner portion of the lamina densa, with gradual tapering of the distribution toward the epithelial side of the basement membrane. The urinary space and epithelial cells were weakly labeled. In tissues from proteinuric patients, albumin was distributed throughout the entire width of the glomerular basement membrane, although the pattern of accumulation varied between patients. The urinary space showed significant labeling associated with some flocculent material. Mesangial areas were heavily labeled in tissues from both control and proteinuric patients. In the latter, lysozomes in glomerular and tubular epithelial cells also accumulated albumin, which is evidence of reabsorption. These results reveal the existence, in normal conditions, of a barrier located in the subendothelial area of the glomerular basement membrane, the loss of which, as in the idiopathic nephrotic syndrome, leads to diffuse distribution of albumin in the glomerular capillary wall. PMID- 2260635 TI - Alternative splicing of endothelial cell fibronectin mRNA in the IIICS region. Functional significance. AB - Transforming growth factor-beta 1 (TGF-beta 1) is thought to play a role in modulating vascular cell function in vivo. In vitro, it decreases endothelial cell proliferation and migration. We postulated that these biologic activities could be mediated through TGF-beta 1 modulation of specific gene expression. Therefore we differentially screened a human umbilical vein endothelial cell cDNA library with cDNAs prepared from both untreated and TGF-beta 1-treated bovine aortic endothelial cells. Using this technique, we isolated many TGF-beta 1 induced cDNA clones. Sequence analysis of these cDNAs showed that many of them corresponded to alternatively spliced fibronectin mRNAs. These fibronectin clones all contained the extradomain I (ED I) but three different forms of the type III connecting segment (IIICS). These different fibronectin cDNAs were expressed in bacteria and the recombinant proteins used to study the effects of IIICS alternative splicing on cell attachment, spreading, and migration in bovine aortic endothelial and smooth muscle cells and B16F10 melanoma cells. The results of these experiments show that attachment and spreading of bovine aortic endothelial and smooth muscle cells depend primarily on the presence of the Arg Gly-Asp-Ser (RGDS) sequence in the recombinant fibronectin proteins. However attachment and spreading of bovine aortic endothelial cells are modulated by alternative splicing in the IIICS region. Specifically splicing of the IIICS region decreases spreading and increases migration rates of the endothelial cells. On the contrary, using a cell line (B16F10 melanoma cells) that is known not to require the RGDS sequence for adhesion confirmed previous findings that B16F10 melanoma cells do not require the presence of the RGDS sequence for attachment and spreading. Indeed B16F10 cells were able to attach and spread on two recombinant proteins that did not contain the RGDS sequence. However attachment and spreading of B16F10 were dramatically inhibited when a 75-base pair DNA fragment was removed from the 5' end of the IIICS region. These results suggest that various regions of the fibronectin molecule may be able to interact with different cell populations to promote cell attachment and spreading, and that alternative splicing may modulate this process. PMID- 2260636 TI - A three-dimensional system for long-term culture of human colorectal adenomas. AB - Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma. PMID- 2260637 TI - Accelerated (proliferative) lupus nephritis. PMID- 2260638 TI - Differential localization of two glucose transporter isoforms in rat kidney. AB - The localization of two glucose transporter isoforms was mapped in the rat kidney: the high-Michaelis constant (Km; 15-20 mM) low-affinity "liver" transporter and the low-Km (1-2 mM) high-affinity "erythroid/brain" transporter. Both are basolateral membrane proteins, but the liver transporter was present exclusively in the S1 part of the proximal tubule, whereas the erythroid/brain transporter was expressed at variable levels in different nephron segments. Staining intensity was low in the straight proximal tubule (S3), intermediate in the medullary thin and thick ascending limbs, and highest in connecting segments and collecting ducts. In the collecting duct, the erythroid/brain glucose transporter was expressed at the highest level in intercalated cells; less was present in principal cells. In the papilla, only intercalated cells expressed this transporter isoform. These results suggest specific involvements of each transporter isoform in transepithelial glucose reabsorption by different segments of the proximal tubule. They also indicate that while the liver glucose transporter is present in gluconeogenic cells, there is a good correlation between the level of expression of the erythroid/brain glucose transporter and the glycolytic activity of the different nephron segments. PMID- 2260639 TI - Adenine nucleotide depletion from endothelial cells exposed to xanthine oxidase. AB - Hypoxia causes breakdown of cellular nucleotides, accumulation of hypoxanthine (HX), and conversion of xanthine dehydrogenase into xanthine oxidase (XO). Upon reoxygenation, the HX-XO reaction generates free radicals, one potential mechanism of tissue damage. Because endothelial cells contain XO and are exposed to circulating HX, they are a likely target for damage. We studied the effect of XO and/or HX at physiologically relevant concentrations on nucleotide metabolism of cultured endothelial cells from human umbilical veins. Cells were labeled with [14C]adenine and incubated for up to 6 h with HX, XO, or both, in the absence or presence of serum. Adenine nucleotides from cell extracts and nucleotide breakdown products (HX, xanthine, and urate) from the medium were separated and counted. HX alone had no effect. XO (80 mU/ml) alone caused a 70% (no serum) or 40% (with serum) fall in adenine nucleotides and an equivalent increase of xanthine and urate. The combination of HX and XO caused a 90% (no serum) or 70% (with serum) decrease in nucleotides, decrease in energy charge, and detachment of cells from the culture plate. Nucleotide depletion was not accounted for by proteolytic activity in the XO preparation. Albumin was only half as effective as serum in preventing nucleotide loss. Thus exogenous XO, in the presence of endogenous HX, triggers adenine nucleotide catabolism, but endogenous XO activity is too low to influence nucleotide levels even at high exogenous HX concentrations. Serum limits the catabolic effect of XO and thus protects cells from free radical damage. PMID- 2260640 TI - Cyclosporin A and vehicle toxicity in primary cultures of rabbit renal proximal tubule cells. AB - The capability of cyclosporin to produce direct injury to primary proximal tubular renal cells was studied. These cells, when grown on Millicell inserts, retain the functional polarity of the proximal tubule, i.e., generate a transepithelial pH gradient (apical compartment acidic) that is reversibly blocked by amiloride addition only if it is added to the apical compartment. Administration of ouabain to the basal compartment also blocks the generation of the transepithelial pH gradient. Additionally, the cells were more responsive to parathyroid hormone (PTH), a proximal tubule characteristic, than to arginine vasopressin (AVP), a distal tubule characteristic. The following substances were tested for their effect on the capacity of these cells to generate a pH gradient: Sandimmune, the commercial form of cyclosporin A; the free form of the drug; Cremophor EL, the vehicle used in the commercial preparation; and ethanol, the vehicle used to dissolve the free form. Sandimmune, at 25-50 microM, inhibited the generation of the pH gradient within 24 h. Surprisingly, Cremophor also blocked the development of a pH gradient, although somewhat less effectively. In contrast, 10 microM cyclosporin, regardless of the form tested, had no effect for up to 96 h. These findings show that cyclosporin, in the form of Sandimmune, has a direct toxic effect on these cells; they also suggest that the vehicle, Cremophor, may contribute to the well-established nephrotoxicity of cyclosporin A. PMID- 2260641 TI - VIP and forskolin enhance carbachol-induced K+ efflux from rat salivary gland fragments by a Ca2(+)-sensitive mechanism. AB - The effect of vasoactive intestinal peptide (VIP) and forskolin on carbachol induced K+ release from superfused rat submandibular and parotid gland fragments was examined using a K(+)-sensitive electrode. Carbachol (0.1, 1, and 10 microM) superfused over the glandular fragments for 15 min caused a concentration dependent, transient elevation of K+ efflux, with a peak value after approximately 5 min. The carbachol-induced release of K+ could be divided into two distinct components, one transient peak lasting 5-8 min independent of extracellular Ca2+ and a second component of K+ release dependent on Ca2+ in the perfusion medium. VIP (1 microM) lacked effect on K+ efflux on its own but increased the carbachol (1 microM)-evoked K+ release. The VIP effects on K+ efflux were mimicked by forskolin (10 microM). Omission of Ca2+ from the medium totally abolished the augmenting effect of VIP and forskolin on carbachol-evoked K+ efflux. The Ca2+ ionophore A23187 (1 or 10 microM) induced a prolonged low rate efflux of K+, which was dependent on Ca2+ in the medium. This effect of A23187 on K+ secretion was potentiated by forskolin (10 microM). The Na(+)-K(+) ATPase blocker ouabain did not affect K+ release on its own, a lack of effect which remained following pretreatment with forskolin. It is concluded that VIP, by increasing the intracellular levels of cAMP in the glandular cell, potentiates carbachol-evoked Ca2(+)-dependent K+ efflux. These results may help to explain the synergistic effects of the coexisting transmitters VIP and acetylcholine. PMID- 2260642 TI - Inhibitory influence of phosphate and arsenate on contraction of skinned skeletal and cardiac muscle. AB - It has been widely observed that Pi decreases maximum calcium-activated force (Fmax) and calcium sensitivity of skinned skeletal and cardiac muscle. However, whether a particular ionic species of Pi (i.e., H2PO4-) is responsible for these effects is controversial. To clarify this issue, we examined the influence of Pi and its structural analogue arsenate (Asi) on contraction of skinned rabbit psoas (fast twitch), soleus (slow twitch), and cardiac papillary muscle. Asi decreased Fmax of all three muscles types to a greater extent than Pi. Both Pi and Asi decreased calcium sensitivity of psoas and cardiac muscles, with Asi having the greater effect. The effect of the protonated form of Pi and Asi on Fmax was evaluated by measuring the response to 30 mM total Pi or Asi at pH 7.4, 7.0, 6.6, and 6.2. In psoas fibers we found that both Pi and Asi were more effective in decreasing Fmax as the pH was lowered (i.e., as the concentration of the diprotonated forms increased). On the contrary, soleus and cardiac fibers did not exhibit this behavior. These differences in the effects of Pi and Asi on Fmax in psoas vs. cardiac and soleus muscles may be related to differences in their myosin heavy chains other than the binding site for the gamma-phosphate of ATP which appears to be conserved for all myosins. PMID- 2260643 TI - Swelling-activated KCl cotransport in rabbit red cells: flux is determined mainly by cell volume rather than shape. AB - The effect of cell shape on ouabain-insensitive 86Rb+ fluxes was examined in rabbit red blood cells. The purpose of the study was to assess the role of mechanical deformations of the membrane in the activation of KCl cotransport by cell swelling. Conversion of cells to echinocytes with low concentrations of amphiphilic agents (anionic and cationic detergents and dipyridamole) in an isotonic medium activates KCl cotransport only very slightly. Hypotonic swelling of echinocytes causes a large increase in KCl cotransport flux just as in swollen discocytes; both the rate and the extent of activation are unaffected by the shape change. Stomatocyte (cup cell) formation with 20 microM chlorpromazine in isotonic medium causes slight activation of KCl cotransport. The KCl cotransport flux induced by cell swelling is approximately 20% higher in swollen stomatocytes than in swollen discocytes. It is concluded that major changes in cell shape have only minor effects on the swelling sensor, signal transduction apparatus, and KCl cotransport protein. We interpret these findings as evidence against the idea that the cell detects its volume by way of a membrane-associated mechanical sensor. As an alternative to a mechanical volume sensor, a hypothetical mechanism for swelling activation of transport is presented in which dilution of the cytoplasm, by mass action alone, can have very large effects on KCl cotransport. PMID- 2260644 TI - Reduction of ferrylmyoglobin in rat diaphragm. AB - The oxidation of myoglobin was monitored by transmission spectroscopy in isolated, superfused preparations of rat diaphragms. In its deoxygenated form, during anoxia, myoglobin was oxidized by adding hydrogen peroxide (1.0 mM) to its ferryl form (FeIV). On the other hand, peroxide-induced formation of ferrylmyoglobin was not observed when the perfusate contained oxygen. Ferrylmyoglobin was visualized after its derivatization with Na2S to form sulfmyoglobin. Depending on the time of addition, ascorbate (4.0 mM) or ergothioneine (2.0 mM) either prevented the formation of or dissipated ferrylmyoglobin. These agents are known to be reductants of this hypervalent form of myoglobin. In addition to providing the first demonstration of ferrylmyoglobin in skeletal muscle, these observations are consistent with the concept that oxidation of myoglobin to hypervalent states might be an important event in the initiation of muscle damage associated with anoxia and reoxygenation. The rapid reduction of myoglobin would prevent peroxidatic alterations of essential cellular constituents by ferrylmyoglobin. PMID- 2260645 TI - [Ca2+]i modulation of Cl- content controls cell volume in single salivary acinar cells during fluid secretion. AB - Differential interference contrast microscopy and low-light-level digital imaging of the fluorescent chloride indicator dye 6-methyl-1-(3 sulfonatopropyl)quinolinium (SPQ) were performed simultaneously in single mammalian salivary gland acinar cells to examine the relationship between cytoplasmic chloride concentration [( Cl-]i) and cell volume during stimulus secretion coupling. Agonist stimulation of Cl(-)-driven fluid secretion is associated with rapid, Ca2(+)-dependent changes of cell volume, which are temporally coupled to changes of [Cl-]i. The agonist-induced changes in [Cl-]i, if accompanied by cations and water, quantitatively account for the cell volume changes, demonstrating in a single cell that cell volume is determined by cell solute content. Agonist-induced modulation of cell volume appears to be a consequence of the requirement to develop appropriate ion gradients necessary for vectorial salt (and fluid) transport. PMID- 2260646 TI - Mechanisms of starvation diabetes: a study with double tracer and indirect calorimetry. AB - To analyze the mechanisms of fasting-induced glucose intolerance, glucose metabolism was studied before and after the ingestion of 75 g glucose in 24 normal subjects fasted for either 14 h (n = 12) or 4 days (n = 12). The techniques included intravenous infusion of [6-3H]glucose and oral administration of [1-14C]glucose combined with indirect calorimetry. Compared with the controls, the starved subjects exhibited the following differences in glucose metabolism during the 5 h after glucose ingestion. 1) Mean incremental levels were fourfold higher for glucose and 40% higher for insulin. 2) Absorption of oral glucose was delayed and prolonged, but total amount reaching systemic circulation in 5 h was identical in the two groups (approximately 63 g). 3) Suppression of hepatic glucose output was reduced (-12 +/- 1 vs. -22 +/- 2 g). 4) Consequently, the increment in peripheral appearance of total glucose (exogenous plus endogenous) was augmented (+ 52 +/- 2 vs. +41 +/- 2 g). 5) Mean glucose clearance increased significantly less (+28 +/- 7 vs. +96 +/- 10 ml/min). 6) Oxidation of oral glucose was reduced (9 +/- 2 vs. 36 +/- 3 g), and nonoxidative disposal (presumably storage) was enhanced (56 +/- 2 vs. 36 +/- 3 g) in the presence of an elevated fat oxidation (35 +/- 2 vs. 22 +/- 4 g). Thus the alterations in glucose homeostasis responsible for the starvation-induced glucose intolerance are located both at the splanchnic (hepatic) and peripheral levels. PMID- 2260647 TI - Parathyroid hormone-related protein and calcium homeostasis in lactating mice. AB - Parathyroid hormone (PTH)-related protein has been shown to be a factor responsible for hypercalcemia of malignancy. Recent studies have shown the presence of mRNA for PTH-related protein in lactating breast tissue, suggesting a physiological role for this peptide during lactation. In the present study, we evaluated the effect of neutralization of PTH-related protein activity in lactating mice (by passive immunization) on various parameters of maternal and neonatal calcium homeostasis. PTH-related protein bioactivity, as tested in the adenylate cyclase assay, was present in mouse milk, and this activity was completely neutralized by the antisera used in the present study. In lactating mice, the effects of injection of PTH-related protein antisera on maternal serum calcium concentrations, milk calcium and phosphorus concentration, pup growth, dam femur calcium content, and pup calcium content were similar to those of the injection of normal rabbit serum. Therefore, maternal PTH-related protein does not appear to have a role in calcium homeostasis during lactation. PMID- 2260648 TI - Measurement of albumin synthesis in humans: a new approach employing stable isotopes. AB - A new method for measuring albumin synthesis in humans with stable isotopes is presented. This can readily be applied in most clinical conditions, even when albumin losses are occurring or when repeated assessment is required. After rapid intravenous injection of a large dose of [13C]leucine (57 mg/kg body wt, 19.4 atoms%), plasma samples were taken at intervals up to 90 min. The enrichment of free leucine in plasma measured by gas chromatography-mass spectrometry rose to a peak at 10 min and then fell slowly, whereas that in liver biopsies (from surgical patients) ranged from 101.5 to 80.5% of the plasma value between 10 and 90 min after injection. The fractional synthesis rate (FSR) was calculated by dividing the increase in enrichment of leucine in albumin, measured by gas isotope ratio mass spectrometry, by the area under the plasma free leucine enrichment vs. time curve after allowing for the period between synthesis of the protein and its secretion into the plasma. The FSR in healthy postabsorptive males was 7.2 +/- 1.3%/day, and the absolute synthesis rate was 157 +/- 39 mg.kg body wt-1.day-1. These rates are comparable to those obtained by other methods. PMID- 2260649 TI - Hepatic uptake and metabolism of oral galactose in adult fasted rats. AB - Galactose is incorporated into glycogen by a different metabolic route than glucose and fructose, the other major dietary monosaccharides. Oral galactose (4 g/kg) was given to 24-h-fasted adult rats to 1) compare quantitatively the disposition of galactose with that of glucose and fructose; 2) examine the effects of galactose on hepatic utilization of other metabolic fuels; and 3) examine circulating and liver galactose concentrations to determine whether net hepatic uptake of galactose, like glucose, occurs against a concentration gradient. Galactose absorption, hepatic blood flow, portal venous, arterial, hepatic venous, and liver concentrations of galactose, glucose, lactate, and alanine, and hepatic glycogen concentrations were measured at intervals up to 240 min. Concentrations entering and exiting the liver, hepatic intracellular concentrations, and net hepatic uptake/output were calculated. Galactose concentration entering the liver increased to a peak of 18.8 +/- 0.8 mumol/ml plasma water at 60 min and then decreased but remained above the control value. Liver galactose concentration increased dramatically from 0.28 +/- 0.04 to 21.2 +/- 1.1 mumol/ml liver water and exceeded plasma concentrations, even during the 1st 120 min when concentration gradients across the liver indicated net galactose extraction. Whole blood galactose concentrations initially were lower and then exceeded plasma concentrations, indicating that erythrocytes maintained galactose concentrations exceeding those in plasma. The data suggest that the hepatic and erythrocyte transport systems for galactose represent active mechanisms. Fifty one percent of absorbed galactose was lost in urine; 18% of the remaining galactose load could be accounted for by net glycogen accumulation. Net increases in galactose, lactate, and alanine uptake could account for the glycogen synthesized but not for the net hepatic glucose output, which changed very little (6% increase). PMID- 2260650 TI - Renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity and mitochondrial phosphate transport in Hyp mice. AB - The Hyp mouse is a homologue of the X chromosome-linked human disease, familial hypophosphatemic rickets (FHR). In FHR, reduced renal tubular brush-border membrane transport of phosphate results in hypophosphatemia and rickets. Both humans with FHR and Hyp mice have abnormal regulation of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase), a mitochondrial enzyme found in proximal renal tubular cell epithelia, the apparent site of defective brush-border membrane phosphate transport. No common pathophysiology for these defects has been demonstrated. We hypothesized that phosphate transport may be present in renal mitochondria from Hyp mice and that its regulation may be deranged in parallel with the mitochondrial 1 alpha-hydroxylase. Using inhibitor-stop techniques described for measurement of phosphate transport in liver mitochondria, we examined mitochondria in normal and Hyp mouse kidney and found them to be comparable. We performed manipulations known to alter 1 alpha hydroxylase differentially in normal and Hyp mice, i.e., phosphorus deprivation and phosphorus loading, and found no effect on mitochondrial phosphate transport. We also subjected Hyp and normal mice to calcium and vitamin D deprivation; this maneuver resulted in no significant changes in mitochondrial phosphate transport in Hyp or normal mice but confirmed the earlier observation that 1 alpha hydroxylase activity is stimulated to a greater degree in normal mice than Hyp mice after this diet. Furthermore, administration of 1,25-hydroxyvitamin D3 depresses 1 alpha-hydroxylase activity in mitochondria from both normal and Hyp mice but has no effect on mitochondrial phosphate transport. We conclude that the mechanism of abnormal vitamin D metabolism in Hyp mice is not related to a primary defect in renal mitochondrial phosphate transport. PMID- 2260651 TI - Phenylalanine flux, oxidation, and conversion to tyrosine in humans studied with L-[1-13C]phenylalanine. AB - Phenylalanine metabolism was determined in 41 studies of adult males (n = 10) consuming an energy-sufficient diet and receiving graded levels of dietary phenylalanine and excess tyrosine (40 mg.kg-1.day-1). After a dietary adaptation period to either 4.2 or 14.0 mg.kg-1.day-1 of phenylalanine; flux, plasma concentration, oxidation, and conversion to tyrosine were measured at test phenylalanine intakes of 5, 7, 10, 14, 21, 28, or 60 mg.kg-1.day-1. Oxidation was low and constant (1.3 mumol.kg-1.h-1) at intakes at or below 10 mg.kg-1.day-1 and increased linearly above this level. Conversion to tyrosine was minimal (2.1%) at these intakes. Breakpoint analysis showed the phenylalanine requirement with excess tyrosine to be 9.1 mg.kg-1.day-1. Plasma phenylalanine concentrations confirmed this estimate of requirement. Prior adaptation did not significantly affect overall flux, plasma concentration, or oxidation nor did it affect the requirement estimate. With the assumption that tyrosine can supply two-thirds of the aromatic amino acid requirement, these data suggest that the aromatic amino acid requirement should be 30 mg.kg-1.day-1 and the World Health Organization recommendation of 14 mg.kg-1.day-1 is an underestimate. PMID- 2260652 TI - Characterization of the process of sodium-calcium exchange in pancreatic islet cells. AB - Na(+)-Ca2+ exchange may play a role in Ca2+ extrusion from the pancreatic B-cell. The characteristics of the process working in its reverse mode were examined in normal rat pancreatic islet cells. Isosmotical replacement of extracellular Na+ by sucrose induced a concentration-dependent increase in 45Ca uptake, displaying a pharmacological sensitivity compatible with an uptake mediated by Na(+)-Ca2+ exchange. Glucose, up to 2.8 mM, stimulated reverse Na(+)-Ca2+ exchange. Likewise, membrane depolarization activated the process but only under raised intracellular Na+ activity. In conclusion, the B-cell Na(+)-Ca2+ exchange displays properties similar to those observed in other cells: reversibility and sensitivity to membrane potential. When working in its reverse mode the exchanger displays a quite large capacity. The role played by the exchanger in the process of insulin release warrants further investigation. PMID- 2260653 TI - Adipocyte lactate production remains elevated during refeeding after fasting. AB - The metabolic state occurring with refeeding after fasting is characterized by the rapid restoration of hepatic glycogen. Recent evidence suggests that a main substrate for glycogenesis is lactate. Because adipose tissue is an active site of lactate production that increases with fasting, we examined the magnitude and duration of lactate production by isolated adipocytes from three adipose depots of rats fasted for 48 h and then refed for up to 96 h. The data show that 48 h of fasting results in a markedly elevated rate of adipocyte lactate production, which increased from 3-9% of total glucose metabolized in the fed state to 49-60% in the fasted state. During the refeeding period, lactate production remained elevated for 12-24 h and then declined. Mesenteric adipocytes had a higher rate and more prolonged elevation in lactate production than cells from the other two depots. We conclude that, with refeeding after a fast, adipocyte glucose conversion to lactate remains elevated during the time of hepatic glycogen restoration. This suggests that adipose tissue may actively produce lactate for glycogenesis during refeeding. PMID- 2260654 TI - Sustained hyperglycemia results in testicular dysfunction and reduced fertility potential in BBWOR diabetic rats. AB - Rats with short-term diabetes show a greater than 50% reduction of serum testosterone and increased lipid in Leydig cells but normal testicular structure. The purpose of this study was to determine the extent of testicular pathology (morphology index), integrity of the blood-testis barrier, daily sperm production (DSP), number of Leydig cells per testis (LC/T), and total trunk testosterone (TTT) in diabetic rats (BBWORdp) with long-term hyperglycemia (300-350 mg/dl for greater than 180 days) and to evaluate its effects on fertility potential. Results were compared with similarly aged normoglycemic rats (BBWORdr) and normal control Wistar rats. After 6 mo of diabetes, testis weights, DSPs, TTTs, and the morphology index were significantly reduced. The LC/T was not different from BBWORdr rats. The blood-testis barrier appeared intact, although structural abnormalities were noted in Sertoli-Sertoli junction complexes. There was a significant reduction in the number of pregnancies per rat and implantations per pregnancy in matings utilizing the diabetic BBWORdp rat and control Wistar female rats. Results indicate that long-term diabetes with sustained hyperglycemia leads to significant testicular dysfunction associated with decreased fertility potential. PMID- 2260655 TI - On the measurement of ketone body turnover. PMID- 2260656 TI - Relationship between portal venous and hepatic arterial blood flows: spectrum of response. AB - The relationship between portal tributary blood flow (PBF) and hepatic arterial blood flow (HAF) was studied in awake, unrestrained rats with the radiolabeled microsphere technique. Six distinct patterns of response emerged. In group A (PBF+, HAF 0), ethanol, acetate, glucagon, prostacyclin, and a mixed diet increased PBF without a change in HAF; in group B (PBF+, HAF+), adenosine and histamine increased both PBF and HAF; in group C (PBF 0, HAF+), isoflurane and triiodothyronine did not change PBF but increased HAF; and in group D (PBF-, HAF+), halothane and vasopressin decreased PBF and increased HAF. Acute partial portal vein ligation decreased PBF (56%) and increased HAF (436%). Hypoxia (7.5% O2) decreased PBF (28%) and increased HAF (110%). In group E (PBF+, HAF-), acute hepatic artery ligation increased PBF (35%) and reduced HAF (74%), while in group F (PBF-, HAF-), thyroidectomy reduced PBF and HAF (36 and 47%, respectively). All blood flow responses were accompanied by the expected changes in both portal tributary and hepatic arterial vascular resistances. The data suggest that the portal and hepatic arterial vascular territories have regulatory mechanisms that allow for independent changes. PMID- 2260657 TI - Inhibition of gastric emptying by acids depends on pH, titratable acidity, and length of intestine exposed to acid. AB - Exposure of the small intestine to acid inhibits gastric emptying in a dose related fashion that depends on titratable acidity and pH. Little information is available on the location of this inhibitory mechanism or on the relative contribution of titratable acidity and pH to this feedback control. We hypothesized that the dependence on titratable acidity is related to the length of the intestine exposed to acid and that the dependence on pH is related to the region of the intestine exposed to acid. To test these ideas, we studied 11 dogs with duodenal and jejunal fistulas. The inhibitory effects were tested when different lengths of the small intestine were exposed to test solutions of 0.03, 0.06, and 0.12 meq/ml titratable acidities. pH as an independent covariable was separated from titratable acidity by comparing the inhibition of gastric emptying of lactic acid (pH fixed to 2.4) to HCl (pH 0.96-1.6). Maximal inhibition of gastric emptying by both acids depended on acid exposure of a length of small intestine that was greater than 65 but less than or equal to 150 cm long. When acid was confined to the proximal 15 cm, increasing concentration of HCl (decreasing pH) resulted in increasing inhibition, but this effect was absent with increasing concentration of lactic acid (fixed pH). Inhibition was absent when 0.06 meq/ml HCl was infused into the intestine beyond the midintestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260658 TI - Inhibition of gastric emptying by sodium oleate depends on length of intestine exposed to nutrient. AB - Previously, we reported that inhibition of gastric emptying by glucose or acids depends on the length of gut exposed to the inhibitor [Gastroenterology 95: A877, 1988; Am. J. Physiol. 256 (Gastrointest. Liver Physiol. 19): G404-G411, 1989]. In this study, we hypothesized that feedback control by fat may be similarly regulated. In dogs with chronic intestinal fistulas, we compared the intensity of intestinal feedback when different lengths of the small intestine were exposed to meals of 3, 9, or 27 mM sodium oleate. We found that 1) inhibition of liquid emptying was dose dependent, 2) intensity of negative feedback was dependent on both the concentration of the oleate and the length of gut exposed to fat, 3) full inhibitory effect was achieved with exposure of fat to 150 cm of gut, 4) inhibition from the distal one-half of gut was less potent than that generated from the proximal one-half of gut, and 5) on a molar basis oleate was 20 times as effective as glucose at inhibition of gastric emptying and that this difference was related to the slower rate of fat absorption. PMID- 2260659 TI - Capsaicin-sensitive afferent fibers contribute to gastric mucosal blood flow response to electrical vagal stimulation. AB - Electrical stimulation of the peripheral vagus produces a noncholinergic increase in gastric mucosal blood flow (GMBF) via unknown mechanisms. The purpose of this study was 1) to investigate whether a portion of the increase in GMBF during prolonged electrical vagal stimulation involves a mechanism separate from augmented acid secretion and 2) to determine whether antidromic activation of afferent fibers contributes to the vascular or secretory responses to electrical vagal stimulation. Electrical vagal stimulation (40 V, 6 Hz, 2 ms) applied for 30 min to the distal cut end of the subdiaphragmatic ventral vagus significantly increased gastric acid secretion and GMBF measured by hydrogen gas clearance. Atropine (0.15 mg/kg iv) or omeprazole (10 mumol/kg iv) completely abolished the secretory response to electrical vagal stimulation, while a significant increase in GMBF remained. Pretreatment with perineural application of the sensory neurotoxin capsaicin to both cervical vagi significantly reduced by 48% the increase in GMBF but not gastric acid secretion; atropine completely abolished the remaining vascular response in capsaicin-treated rats. These results suggest that prolonged electrical vagal stimulation induces a sustained increase in GMBF partially independent of augmented acid secretion and that the noncholinergic portion of the vascular response is mediated by capsaicin-sensitive vagal afferent fibers. PMID- 2260660 TI - Na+ transport properties of isolated rat parotid acini. AB - The effect of carbachol stimulation on the Na+ transport properties of rat parotid acini was characterized. Upon stimulation, the acinar Na+ concentration increased from 20 to 70 mM within 25 s, whereafter a backregulation toward the prestimulatory level was observed, mediated by the Na(+)-K+ pump. The transport mechanisms responsible for the net Na+ uptake observed between 10 and 20 s after carbachol stimulation in a Krebs-Ringer-bicarbonate medium (KRB) consisted of a dimethylamiloride-sensitive Na(+)-H+ exchange system (3.5 mmol.liter cell water 1.s-1 or approximately 75% of the total Na+ influx) and a bumetanide-sensitive cotransport system (of approximately 15%). The data are consistent with the residual influx being mediated by amiloride-sensitive Na+ channels. In unstimulated acini acidified by a NH4+ prepulse technique, the relationship between intracellular pH (pHi) and the rate of acinar Na(+)-H+ exchange was determined. At pHi 6.5 the rate of Na(+)-H+ exchange in a KRB medium amounted to 1.2 mmol.liter cell water-1.s-1 and ceased when pHi had recovered to 7.2. It was concluded that under physiological conditions carbachol stimulation activates Na(+)-H+ exchange, an effect that is responsible for the major part of the Na+ gain after stimulation. The role of cotransport in mediating net Cl- uptake against an electrochemical gradient was investigated. It was found that when the Na+ gradient is strongly reduced (in a 20 mM Na+ medium) a Cl(-)-HCO3- exchange system can mediate a net Cl- uptake at a rate similar to the rate observed in a medium containing high Na+. The results are compatible with both Cl(-)-HCO3- exchange and cotransport keeping an intracellular Cl- concentration above the electrochemical equilibrium under physiological conditions. PMID- 2260661 TI - Identification and partial characterization of multiple forms of biologically active EGF in rat milk. AB - Milk from lactating Sprague-Dawley rats was assayed for epidermal growth factor (EGF)-like activities. A homologous radioimmunoassay (RIA) indicated the presence of immunoreactive material that competed in a nonparallel fashion with submandibular gland rat EGF (sm-r-EGF). The activity in the milk was extracted using antibodies to sm-r-EGF covalently linked to acrylamide beads. This activity was characterized by RIA, nondenaturing polyacrylamide gel electrophoresis, enzymatic digestion, radioreceptor assay, and ability to stimulate incorporation of [3H]thymidine into cultured fibroblasts. The presence of three distinct immunoreactive forms of EGF in rat milk were detected that competed with 125I labeled r-EGF for binding to the EGF receptor and stimulated DNA synthesis in growth-arrested fibroblasts. Two of the forms are converted to the sm-r-EGF species by tryptic digestion as determined by RIA and migration rates in a nondenaturing polyacrylamide gel. The biological activities are stable to heating in 0.1 M acetic acid and also are stable at pH 9.0. Levels of r-EGF equivalents in milk were low at time of birth (6.3 +/- 1.7 ng/ml) and rose to 35.4 +/- 14.6 by days 4 to 6. PMID- 2260662 TI - Visualization and characterization of gastric contractions using a radionuclide technique. AB - With the use of the radionuclide gastric-emptying test and a new data processing method, the contraction characteristics of the stomach were analyzed. After ingestion of a radiolabeled test meal, dynamic images of the stomach were acquired and analyzed to determine the frequency, amplitude, and rate of gastric contractions in healthy subjects. The frequency of antral contractions was found to be inversely related with food retention in the stomach; in contrast, the amplitude of the contractions decreased progressively during the course of gastric emptying. The peaks of both antral contraction and filling rate and the time of their occurrence remained constant throughout gastric emptying. The observed patterns of phase distribution and sequential phase changes of the food in the stomach confirmed noninvasively what was already known from invasive technique, i.e., that the proximal stomach does not undergo phasic contractions and that, in the distal stomach, smooth muscle contraction originates in midcorpus and propagates aborally to the pylorus. The scintigraphic test can be used to noninvasively and quantitatively characterize gastric motor function and to delineate the spatial sequence of gastric contractions. This technique can be applied to study the pathophysiology of gastric emptying in various motor disorders. PMID- 2260663 TI - Regulation of canine jejunal transit. AB - The aim of this study was to determine what factors influence the direction of movement of canine jejunal chyme. In four dogs, pacing electrodes were implanted near each end of a 50-cm jejunal Vella loop, while recording electrodes and intraluminal pressure catheters were spaced along the loop. After recovery, the loop was perfused from either the proximal stoma (forward flow) or the distal stoma (reversed flow), and effluent was collected from the nonperfused stoma. The pacesetter potentials were paced electrically in a forward (aborad) or a reverse (orad) direction. During control conditions (forward flow-forward pacing), the mean transit time of liquids was 2.6 +/- 0.1 min (mean +/- SE) and the static volume of the loop was 8.8 +/- 0.3 ml. Reversing both direction of flow and direction of pacesetter potential propagation slowed transit (4.4 +/- 0.4 min; P less than 0.05) and increased loop volume (16.0 +/- 1.0 ml; P less than 0.01). Reversing flow with forward pacing resulted in even slower transit (7.5 +/- 1.2 min; P less than 0.05), maintained a large volume (33 +/- 10 ml), and increased basal pressure in the loop from -1.2 +/- 1.7 (control) to 2.3 +/- 1.6 mmHg (P less than 0.05). These observations suggest that the direction of propagation of jejunal pacesetter potentials influences the direction of movement of jejunal chyme but that other factors have a role as well. PMID- 2260664 TI - Cerebral potentials evoked by esophageal distension in human. AB - Recent studies have shown that cerebral evoked potentials (EPs) can be recorded after balloon distension of the human esophagus. The aim of this study was to evaluate the characteristics of these viscerosensory EPs and to investigate the relations between these EPs and perception of esophageal distension. Nineteen healthy volunteers (22-60 yr old) were studied. A balloon positioned 5 cm above the lower esophageal sphincter was inflated 10 times each minute. EPs recorded from four midline scalp electrodes were averaged for 50 and 100 inflation cycles. A clearly defined triphasic (negative-positive-negative) EP was recorded in all subjects and from all four recording sites when a volume leading to definite sensation and rapid balloon inflation (170 ml/s) was used. The latencies of the peaks were 231 +/- 7 (N1), 303 +/- 7 (P1), and 379 +/- 8 ms (N2). No significant correlation between stimulus perception and latency was found. The amplitude and quality of the EPs (scored by 3 blinded observers) increased significantly (P less than 0.01, ANOVA) with increasing sensation. Slow balloon inflation (30 ml/s) was significantly less effective in evoking EPs than rapid inflation (P less than 0.01). The EPs evoked by 100 inflations were not significantly clearer than those evoked by 50 inflations. It is concluded that the ability to record cerebral potentials evoked by esophageal balloon distension is related to the rate of balloon inflation and to the level of awareness of the stimulus. PMID- 2260665 TI - Hormonal mechanism of sodium oleate-stimulated pancreatic secretion in rats. AB - We have investigated the role of two intestinal hormones, secretin and cholecystokinin (CCK), on the pancreatic exocrine secretion stimulated by sodium oleate in anesthetized rats. Each rat was prepared with a polyethylene tube in the proximal duodenum and ligation of the pylorus. To collect pancreatic juice, the common bile-pancreatic duct was cannulated near the duodenal wall while bile was diverted to the exterior. Intraduodenal infusion of sodium oleate at doses of 0.03, 0.06, 0.12, and 0.24 mmol/h resulted in significant increases in pancreatic secretion including fluid, bicarbonate, and protein output. The increases of the three parameters were dose dependent and were correlated well with the increases in plasma secretin and CCK concentrations. To further clarify their hormonal roles, we have repeated identical experiments under intravenous administration of a rabbit anti-secretin serum (0.1 ml) or CR 1409 (4 mg.kg-1.h-1), a CCK-receptor antagonist, or a combination of both the antiserum and CR 1409. The antiserum significantly suppressed volume flow and bicarbonate secretion with a minor inhibitory effect on protein secretion, whereas a normal rabbit serum did not. CR 1409 significantly suppressed all three parameters. The combined treatment with both the antiserum and CR 1409 almost completely abolished the pancreatic secretion. Atropine given intravenously significantly inhibited the protein output but did not influence volume flow or bicarbonate output in response to sodium oleate. We thus conclude that, in rats, fat-stimulated pancreatic secretion of volume flow and bicarbonate depends entirely on the circulating endogenous secretin and CCK but that the protein output appears to be under control of both hormonal and cholinergic controls. PMID- 2260666 TI - Cation current activated by hyperpolarization (IH) in guinea pig enteric neurons. AB - Intracellular microelectrode and whole cell patch-clamp recordings were made from guinea pig enteric neurons in vitro. In most myenteric AH neurons (but not S neurons), step hyperpolarizations from the resting potential evoked an inward current (IH). IH peaked in approximately 400 ms (at 36 degrees C), was fully activated at -100 mV, and did not inactivate during 10 s. IH was associated with a conductance increase and reversed polarity at about -40 mV (by extrapolation). IH was reduced in low-sodium concentrations and increased when the concentration of extracellular potassium ions was increased. Cesium (2 mM) blocked IH in a voltage-dependent manner; this led to an increase in the amplitude of the spike after-hyperpolarization. Cobalt (2-4 mM) or barium (0.01-1 mM) did not alter IH. Only 12% of submucous plexus neurons showed IH and this subgroup included both S and AH neurons. In myenteric AH neurons, IH would act in opposition to the persistent calcium-activated potassium current and thus stabilize the resting potential. PMID- 2260667 TI - Relationship between enteric migrating motor complex and the sleep cycle. AB - To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other. PMID- 2260668 TI - Cytoskeleton of intestinal goblet cells: role of actin filaments in baseline secretion. AB - Although microtubules appear necessary to maintain mucin granule transport in intestinal goblet cells, the role of microfilaments in mucus secretion is unknown. To determine the functional significance of microfilaments in goblet cell secretion, fluorescent cytochemistry of microfilaments and autoradiographic studies on granule movement were performed on rabbit intestinal goblet cells, with and without the actin depolymerizing agents, cytochalasin D (cyto D), and dihydro-cytochalasin B (dihydro B). In normal goblet cells, cytochemical localization of F-actin with NBD-phallacidin demonstrated their restriction to the apical surface of the goblet cell. Visualization of the goblet cell apical surface by electron microscopy revealed the presence of a thin layer of cytoplasm overlying the granule mass. Treatment with cyto D and dihydro B eliminated NBD phallacidin staining of the apical cell surface. Quantitative analysis of baseline granule translocation demonstrated that treatment with cyto D and dihydro B resulted in dramatic acceleration of granule movement through goblet cells. This cellular response results from an increase in baseline secretion and facilitation of secretion of newly synthesized mucins, not stimulation of an accelerated secretory event. These data imply that actin filaments fulfill a barrier function in baseline secretion by hindering granule access to the plasma membrane; once the granule contacts the plasma membrane, exocytosis occurs. Secretion is balanced by the translocation of subjacent granules. In contrast, an accelerated secretory event is not triggered by plasma membrane access alone; this event requires a regulatory signal. We hypothesize that, unlike accelerated secretion, baseline secretion is constitutive, with exocytosis limited solely by the physical constraint of secretory granule access to the apical plasma membrane. PMID- 2260669 TI - Regulation of fetal lung maturation. AB - The recent identification of the genes for the surfactant proteins has greatly facilitated the study of the regulation of fetal lung alveolar epithelial cell development at the molecular level. In general, expression of the genes for the surfactant proteins is enhanced by the same hormones that stimulate phospholipid synthesis. There are, however, some notable differences that indicate that the genes for the different components of surfactant are independently regulated. Species differences in the response of the surfactant proteins to hormones such as glucocorticoids and adenosine 3',5'-cyclic monophosphate have also been demonstrated. This review focuses on current knowledge of the hormonal regulation of the surfactant proteins against a background of previous studies of lung development. PMID- 2260670 TI - Ultrastructural analysis of regional type II cell development within fetal and neonatal lungs. AB - Type II cells within guinea pig lungs were studied beginning when lamellar bodies (LB) were first identifiable, to determine the pattern of their ultrastructural maturation through parturition and to search for regional differences suggested for other species in their numbers or maturity within the same lung. Fetuses were examined at gestational ages of 55, 60, and 65 days, as were newborn within 2 h of birth at 68 days. The stratified sampling system divided left lungs into nine blocks from each cranial and caudal lobe for electron-microscopic morphometry. Type II cells were compared among blocks within lobes, between lobes within age groups, and among ages for volume densities [VV(ep2, t)], numerical densities [NV(ep2, t)], and surface densities [SV(ep2, t)] per block; total tissue volumes [V(ep2)], numbers [N(ep2)], and cumulative surface areas [S(ep2)] per lung; and the VV(lb, ep2) and V(lb) of their LB. Within lobes, there were no significant differences among blocks for any parameter. Within age groups, significant interlobar differences were limited only to NV(ep2, t) (cranial greater than caudal at day 55, P less than 0.001). In age-by-age comparisons, the V(ep2), NV(ep2), and S(ep2) each increased dramatically from day 55 to 60 (P less than 0.001) but then remained unchanged through parturition. However, both VV(lb, ep2) and V(lb) increased linearly with fetal age (day 55 less than 60 less than 65 less than newborn), with VV(lb, ep2) achieving 18% type II cell volume in the postpartum group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260671 TI - Mechanical removal of airway epithelium disrupts mast cells and releases granules. AB - Many previous investigators have utilized mechanical rubbing as a method for examining effects of epithelial removal. In the present study, we examined whether this procedure also affects mast cell integrity in the underlying lamina propria. We isolated bronchial rings from six ferrets, and we found that removal of epithelium by rubbing decreased the total number of intact mast cells from 10.0 +/- 1.9 to 2.2 +/- 0.6 (SE) mast cells/mm luminal perimeter (P less than 0.01). In addition, we found a very large number of metachromatic particles that appeared to be mast cell granules unassociated with identifiable mast cells. Their identity was confirmed the presence of free mast cell granules and showed that they contained intact membranes. These effects were not observed when the epithelium was removed by enzymatic digestion, but they were observed after mechanical deformation of the bronchi alone. We suggest that mast cell components released by removing or damaging the epithelium may affect the function of various cells in the airway. PMID- 2260672 TI - Attenuation of acid aspiration edema with phalloidin. AB - Acid aspiration leads to pulmonary endothelial and epithelial cell (EC/EpC) injury characterized by increased permeability and polymorphonuclear (PMN) leukocyte diapedesis. Actin in the EC/EpC cytoskeleton has been shown to play a significant role in maintenance of the microvascular junction barrier. This study tests indirectly whether the development of permeability and diapedesis following acid aspiration is via disruption of the pulmonary cytoskeleton. Manipulation was achieved by the actin microfilament assembler phalloidin. Anesthetized rats (n = 88) underwent segmental lung installation of 0.1 ml saline or phalloidin (2 x 10( 6) M). Twenty minutes later 0.1 N HCl, saline, or phalloidin was introduced. After 3 h there was an increase in wet-to-dry weight (W/D) ratio of 6.6 and 5.1 in the HCl-injected and noninjected sides, protein concentration, 3,970 and 2,530 micrograms/ml, and accumulation of 93 PMN/ml (x 10(4] in bronchoalveolar lavage (BAL) of the HCl-injected lung. These values were higher than control animals. Local pretreatment with phalloidin attenuated acid-induced localized but not generalized permeability with reduction in W/D ratio, BAL protein concentration, and diapedesis (P less than 0.05). Acid injection into airways also led to elevated thromboxane B2 and leukotriene B4 levels in plasma and BAL (P less than 0.05) and generalized lung leukosequestration, events not affected by phalloidin. Taken together, these data suggest that acid aspiration lung injury is determined largely by loss of integrity of the pulmonary EC/EpC cytoskeleton with resultant loss of barrier function. PMID- 2260673 TI - Potassium currents in canine airway smooth muscle cells. AB - The electrical properties of dissociated canine tracheal smooth muscle cells were examined using the whole cell patch-clamp technique. In current clamp mode, current clamp steps did not initiate action potentials but showed clear outward rectification, which was abolished when cells were loaded with Cs+ ions and when tetraethylammonium (TEA+) ions replaced Na+ in the bath solution. In voltage clamp experiments, depolarizations positive to -45 mV evoked brief voltage dependent inward Ca2+ currents [Am. J. Physiol. 254 (Cell Physiol. 23): C793 C801, 1988], followed by sustained outward currents, which did not completely inactivate. Outward currents were identified as K+ currents on the basis of the reversal potential of the current and by ion-substitution experiments. The currents were further defined as Ca2(+)-insensitive delayed rectifier currents, since they were unaltered under conditions in which 1) the Ca2+ current was completely blocked by Mn2+ or nifedipine (10 microM); 2) Ba2+ ions were substituted for Ca2+ as the inward current charge carrier; or 3) charybdotoxin (40 nM) or TEA+ (up to 10 mM) were added to the bath. A Ca2(+)-activated potassium [K(Ca)] current was activated by application of methacholine (100 microM), or A23187 (1 microM), under conditions of low Ca2+ buffering capacity in the internal solution [0.3 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA)]. The K(Ca) current was blocked by 10 mM TEA+ and was not observed under conditions of high intracellular Ca2+ buffering (11 mM EGTA). These data indicate that canine airway smooth muscle cells contain voltage dependent delayed rectifier channels that underlie membrane rectification and K(Ca) channels that are activated by agents which release intracellular Ca2+ stores. PMID- 2260674 TI - Virus-induced alterations in macrophage production of tumor necrosis factor and prostaglandin E2. AB - The cellular immune response to respiratory syncytial virus (RSV) is felt to contribute to viral clearance and/or the inflammation accompanying pulmonary infections with this virus. Both tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) are important regulatory mediators of the cellular immune response. We examined the production of these mediators from purified human alveolar and blood mononuclear phagocytes (MP) after RSV infection in vitro and compared production induced by virus with that induced by lipopolysaccharide (LPS). RSV infection of alveolar MP did not alter PGE2 production but increased expression of TNF alpha mRNA paralleled by increased secretion of immunoreactive and biologically active TNF. TNF production by alveolar MP was dependent on the infectious dose of virus and occurred early in the viral replication cycle. In contrast, RSV had minimal effects on blood MP production of TNF and PGE2. However, blood MP (and not alveolar MP) infected with RSV and costimulated with LPS demonstrated a 1.7-fold increase in PGE2 levels compared with LPS alone (P less than 0.001). Therefore, RSV has differential effects on human alveolar and blood MP production of these immunoregulatory molecules. PMID- 2260675 TI - A novel epithelial cell from neonatal rat lung: isolation and differentiated phenotype. AB - A novel epithelial cell from normal neonatal rat lung has been isolated, established, and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutrition/hormonal microenvironment, we have been able to select, from a heterogeneous population, a single epithelial cell type that can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for greater than 2 yr in continuous culture. It has been characterized by ultrastructural, morphological, and biochemical criteria. The basal medium for this cell line is Ham's F12/Dulbecco's modified Eagle's (DME) medium plus insulin (1 micrograms/ml), human transferrin (10 micrograms/ml), ethanolamine (10(-4) M), phosphoethanolamine (10(-4) M), selenium (2.5 x 10(-8) M), hydrocortisone (2.5 x 10(-7) M), and forskolin (5 microM). The addition of 150 micrograms/ml of bovine pituitary extract to the defined basal medium stimulates a greater than 10-fold increase in cell number and a 50- to 100-fold increase in thymidine incorporation. The addition of retinoic acid results in further enhancement of cell growth and complete inhibition of keratinization. We have demonstrated a strategy that may be applicable to isolating other cell types from the lung and maintaining their differentiated characteristics for long-term culture in vitro. Such a culture system promises to be a useful model in which to study cellular events associated with differentiation and proliferation in the lung and to better understand the molecular mechanisms involved in these events. PMID- 2260676 TI - Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia. AB - The Fischer rat is known for its susceptibility to develop liver necrosis when challenged with paraquat (Smith et al., J. Pharmacol. Exp. Ther. 235: 172-177, 1985). We postulated that other organs, specifically the lung, may also be more susceptible to injury and examined whether lungs from Fischer (F) rats were injured more easily when challenged with active oxygen species than Sprague Dawley (SD) rat lungs. We aimed to investigate whether increased susceptibility to oxidant injury was related to differences in lung antioxidant defenses. Perfused lungs from both rat strains were challenged by addition of H2O2 to the perfusate or by short-term hyperoxic ventilation. To assess nonoxidant modes of lung injury, we examined lung responses after exposure to protamine sulfate or neutrophil elastase. Intravascular H2O2 or 3 h in vitro hyperoxia caused lung edema in F but not SD rats, and elastase injured F rat lungs more than the lungs from SD rats. Protamine, however, injured the lungs from both strains to a similar degree. Catalase, but not superoxide dismutase or allopurinol, protected F rat lungs against edema, resulting from 3 h in vitro hyperoxia. The lung homogenate levels for reduced glutathione or conjugated dienes and the activities of lung tissue catalase, glutathione peroxidase, and cytochrome P-450 were not different between the two strains. Lung tissue ATP levels, however, were lower in F than in SD rats. Although the F rat strain appears to have an altered oxidant antioxidant defense balance, the exact cause of the greater susceptibility to oxidant stress of the F rat strain remains elusive. PMID- 2260677 TI - Mechanisms of sodium and chloride transport across equine tracheal epithelium. AB - Equine tracheal epithelium, stripped of serosal muscle, mounted in Ussing chambers, and bathed in plasmalike Ringer solution generates a serosa-positive transepithelial potential of 10-22 mV and a short-circuit current (Isc) of 70-200 microA/cm2. Mucosal amiloride (10 microM) causes a 40-60% decrease in Isc and inhibits the net transepithelial Na flux by 95%. Substitution of Cl with gluconate resulted in a 30% decrease in basal Isc. Bicarbonate substitution with 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid decreased the Isc by 21%. The Cl-dependent Isc was inhibited by serosal addition of 1 mM amiloride. Bicarbonate replacement or serosal amiloride (1 mM) inhibits the net Cl flux by 72 and 69%, respectively. Bicarbonate replacement significantly reduces the effects of serosal amiloride (1 mM) on Isc, indicating its effect is HCO3 dependent. Addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 100 microM) causes a 40% increase in Isc. This effect is inhibited by subsequent addition of 10 microM serosal bumetanide. Bumetanide (10 microM) reduces net Cl secretion following stimulation with 8-BrcAMP (100 microM). Serosal addition of BaCl2 (1 mM) causes a reduction in Isc equal to that following Cl replacement in the presence or absence of 100 microM cAMP. These results suggest that 1) Na absorption depends on amiloride-inhibitable Na channels in the apical membrane, 2) Cl influx across the basolateral membrane occurs by both a Na-H/Cl-HCO3 parallel exchange mechanism under basal conditions and by a bumetanide-sensitive Na-(K?)-Cl cotransport system under cAMP-stimulated conditions, and 3) basal and cAMP-stimulated Cl secretion depends on Ba-sensitive K channels in the basolateral membrane. PMID- 2260678 TI - Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities. AB - Tracheal insufflation of tumor necrosis factor (TNF) enhances pulmonary antioxidant enzyme activities and protects rats against oxygen toxicity (J. Appl. Physiol. 68: 1211-1219, 1990). We now report that tracheal insufflation of TNF selectively induced pulmonary Mn-superoxide dismutase (SOD) mRNA in normoxia- and hyperoxia-exposed rats, leading to increased amounts of Mn-SOD specific protein and enzyme activity. Tracheal insufflation of TNF had no effect on the levels of pulmonary Cu,Zn-SOD mRNA or specific protein. Hyperoxia alone also selectively induced pulmonary Mn-SOD mRNA. However, the hyperoxia-induced increase in Mn-SOD mRNA was not associated with an increase in Mn-SOD specific protein or enzyme activity. The results suggest that the increased pulmonary Mn-SOD in TNF insufflated rats may contribute to the TNF-induced protection against oxygen toxicity. PMID- 2260679 TI - Effect of acute pH change on mitochondrial glutamine transport. AB - The uptake of [3H]glutamine in submitochondrial particles (SMP) was measured at varying medium pH. Glutamine transport, but not glutamine binding, was inversely related to medium pH (range 6.5-8.5). Glutamine uptake was highest at medium pH of 6.5 (4.59 +/- 0.4 pmol.mg-1.30 s-1) and lowest at medium pH of 8.0 (1.99 +/- 0.3 pmol.mg-1.30 s-1). The effect of medium pH on glutamine transport was rapidly reversible. Changes in pH gradient (delta pH) had no influence on the rate of glutamine transport. Kinetics of mitochondrial glutamine transport was studied at pH 6.5 and 8.5 to further elucidate the mechanism by which pH alters glutamine transport. Glutamine concentration at half-maximal velocity ([S]0.5) was 9.07 and 13.32 mM at pH 6.5 and 8.5, respectively (P less than 0.02). The maximal velocity (Vmax) was 1,417.72 +/- 185.69 pmol.mg-1.15 s-1 at pH 6.5 and 910.95 +/- 192.85 pmol.mg-1.15 s-1 at pH 8.5 (P less than 0.01). Thus both the affinity and the Vmax of the transport system were enhanced in acidic pH. These data imply that intracellular pH has influence over glutamine transport into the mitochondrial matrix and, consequently, renal NH3 production. Glutamine delivery to the matrix via changes in cytosolic pH may be one of the regulators for ammoniagenesis during acute acid-base disorders. PMID- 2260680 TI - Angiotensin II regulates renin gene expression. AB - We investigated the effect of angiotensin II (ANG II) and enalapril on accumulation of renin messenger RNA (mRNA) and on renal renin distribution (immunohistochemical analysis). Adult Wistar-Kyoto rats received enalapril (0.2 mg/ml) in distilled drinking water for 8 or 12 days. On day 5 of enalapril treatment, an osmotic minipump was implanted in the peritoneum that caused sustained release of ANG II (200 ng.kg-1.min-1) or vehicle (bovine serum albumin) for 3 or 7 days. Control rats received water for 8 or 12 days and osmotic minipump implantation (containing vehicle solution) on the 5th day. Renin mRNA was identified by hybridization with a 32P-labeled full-length complementary DNA and was detected by autoradiography. Enalapril treatment increased renal renin mRNA specific activity (renin mRNA/total RNA). Subsequent infusion of angiotensin II for 3 or 7 days decreased renal renin mRNA specific activity. In addition, renin immunostaining increased along the afferent arteriole after enalapril treatment; however, enalapril-induced spread of renin immunostaining was not inhibited by ANG II. Thus ANG II attenuates the accumulation of renin mRNA stimulated by enalapril treatment without alteration of renal renin distribution. The lack of effect of ANG II on renal renin distribution may be due to the length of turnover time for stored protein. These findings suggest the shortloop negative feedback of ANG II on renin reflects inhibition of renin synthesis by ANG II. Therefore, we propose that ANG II exerts a direct inhibitory effect on renin by regulation of renin gene expression in renal vasculature. PMID- 2260681 TI - Electrical properties of smooth muscle cell membrane in renal pelvis of rabbits. AB - Intracellular recordings were made to study the electrical properties of smooth muscle cells in the rabbit renal pelvis. The muscle cells exhibited spontaneous oscillation in the membrane potential (slow wave). The slow waves were regular and were resistant to tetrodotoxin and sympathomimetic or parasympathomimetic antagonists, findings indicative of myogenic activity. The membrane was depolarized by an increase in extracellular concentration of K+ ([K+]o), decrease in [Na+]o, inhibition of the electrogenic Na(+)-K+ pump by ouabain or K(+)-free solution, and the application of norepinephrine (NE, greater than 10(-6) M). The maximum slope of the membrane depolarization produced by a 10-fold increase in [K+]o was approximately 48 mV. Reductions in [Ca2+]o inhibited the generation of slow waves with no marked change in the membrane potential. Depolarizations produced by any given method increased the frequency and decreased the amplitude of the slow wave, and NE had the most potent accelerating action on the frequency. Hyperpolarization of the membrane by 1-5 mV with extracellularly applied current stimuli reduced the frequency, and a strong hyperpolarization (greater than 5 mV) blocked the generation of slow waves. Electrophysiological properties of the slow waves obtained with tissues of the renal pelvis and intestinal smooth muscles were compared. PMID- 2260682 TI - Postnatal development of oxidative enzymes in various rat nephron segments: effect of weaning on different diets. AB - Activities of fumarase and 3-hydroxyacylCoA dehydrogenase (3-OHDH) were determined in homogenates of rat kidneys between day 21 of gestation and postnatal day 10 and in single isolated nephron segments at postnatal days 16, 21, and 30, and in adult segments. For 3-OHDH activity, main developmental changes were found in proximal convoluted (PCT) and straight tubules (PST) and were characterized by an overshoot of adult level from postnatal days 21 to 30 (59.7 +/- 3.0 and 37.5 +/- 3.4 at day 21 vs. adult values 27.1 +/- 1.5 and 22.7 +/- 1.5 mol.kg dry wt-1.h-1). When rats were precociously weaned on day 16 and fed a diet containing lipid to equal 13% of total caloric intake, a significant decrease in 3-OHDH activity was observed in some parts of the nephron. These changes could be prevented by maintaining early weaned animals on high-fat diet providing 70% of total calories as lipid. Results suggest that changes in fat content of diet during kidney maturation can in part regulate 3-OHDH activity in some nephron segments. Fumarase activity increased 2.6-fold in the medullary thick ascending limb between days 16 and 30; pattern of development was similar to the one reported for Na(+)-K(+)-ATPase activity in this segment. High levels of both enzymes were reached noticeably earlier during development in PCT and PST than in medullary thick ascending limb, which emphasizes metabolic heterogeneity of developing rat kidney nephron. PMID- 2260683 TI - Cell pH regulation in rabbit outer medullary collecting duct cells: mechanisms of HCO3(-)-independent processes. AB - To clarify mechanisms of intracellular pH (pHi) regulation in outer stripe of outer medullary collecting duct (OMCDOS), isolated perfused OMCDOS of the rabbit were loaded with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and single cell pHi was monitored by an image processing system. Initial pHi recovery rates (dpHi/dt, pH unit/s x 10(3)) after intracellular acid load made by NH4Cl prepulse were determined. In the absence of exogenous CO2-HCO3-, dpHi/dt was 12.3 +/- 0.9 (means +/- SE) in principal cells (PC), and 11.5 +/- 1.0 in intercalated cells (IC). In PC, total ambient Na+ removal halted pHi recovery (dpHi/dt = 0.6 +/- 0.5), and pHi recovered when Na+ was added to the basolateral (dpHi/dt = 14.7 +/- 0.8) but not to the luminal (dpHi/dt = 0.9 +/- 0.5) solutions. This bath Na+ effect was amiloride inhibitable. In IC, pHi recovered (dpHi/dt = 6.4 +/- 0.3) in the absence of ambient Na+. This pHi recovery was significantly reduced by luminal 0.5 mM N-ethylmaleimide (NEM) or 0.5 mM N,N'-dicyclohexylcarbodiimide (DCCD). Basolateral NEM or DCCD had no significant effect. Basolateral addition of Na+ significantly accelerated the pHi recovery. These data suggest the presence of basolateral Na(+)-H+ exchange in both PC and IC, and luminal NEM- and DCCD-sensitive H+ pump in IC of rabbit OMCDOS. PMID- 2260684 TI - Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex. AB - Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Fromter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex. PMID- 2260685 TI - Localization of arginine synthesis along rat nephron. AB - Arginine production was measured in isolated rat nephron segments. Segments were incubated with 0.3 mM aspartate and 0.1 mM L-[ureido-14C]-citrulline in a sealed chamber. Arginase and urease were added to the medium to hydrolyze arginine and to release 14CO2, which was trapped in KOH and counted. Arginine synthesis was found only in the proximal tubule, with decreasing intensity from proximal convoluted (PCT) to proximal straight tubule (PST). Results were as follows (in fmol.min-1.mm tubule length-1): PCT, 122 +/- 15; cortical PST, 71 +/- 6; outer medullary PST, 41 +/- 4; all other segments, less than 6. Arginine synthesis changed almost proportionally with precursor concentration of less than or equal to 0.4 mM. We had shown previously that PST but not PCT was able to hydrolyze arginine into urea and ornithine. In this study arginine was further hydrolyzed in cortical (40%) and medullary (64%) PST but not in PCT. These observations suggest that the arginine formed in PCT contributes to the maintenance of the whole body arginine pool, whereas most of the arginine formed in PST might contribute, by its conversion to urea, to the process of urine concentration. PMID- 2260686 TI - Renal effects of moderate hemorrhage in the conscious pregnant rat. AB - Studies were performed in conscious, chronically catheterized virgin, 8- to 9-day pregnant, and 15- to 16-day-pregnant Sprague-Dawley rats in baseline state and after removal of 7.5% total blood volume. Measurements were made of glomerular filtration rate (GFR), renal plasma flow (RPF), renal vascular resistance (RVR), arterial blood pressure (AP), and urinary electrolyte excretion. In baseline state, GFR and RPF were elevated at days 8-9 and days 15-16 of pregnancy (vs. virgins) due to a gestational renal vasodilation. The fall in hematocrit indicates substantial plasma volume expansion by days 15-16 of pregnancy. After removal of 7.5% total blood volume, little change occurred in AP in any group. However, the renal vasculature provided a sensitive response to moderate hemorrhage, since RPF fell and RVR increased similarly in virgin, 8- to 9-day- and 15- to 16-day-pregnant rats. GFR was protected in virgin and 8- to 9-day pregnant rats but fell significantly in late pregnancy. Urinary electrolyte excretion tended to fall but was not significantly reduced by hemorrhage in any group. These studies indicate that renal vascular response to moderate hemorrhage is similar in virgin, early, and late pregnancy. Thus effector mechanisms that sense volume and regulate RVR must be continually reset to respond to progressive plasma volume expansion of pregnancy as normal. PMID- 2260687 TI - Dihydropyridine-sensitive cell volume regulation in proximal tubule: the calcium window. AB - The mechanism underlying the activation of hypotonic cell volume regulation was studied in rabbit proximal straight tubule (PST). When isolated non-perfused tubules were exposed to hypotonic solution, cells swelled rapidly and then underwent a regulatory volume decrease (RVD). The extent of regulation after swelling was highly dependent on extracellular Ca concentration ([Ca2+]o), with a half-maximal inhibition (K1/2) for [Ca2+]o of approximately 100 microM. RVD was blocked by the Ca-channel blockers verapamil, lanthanum, and the dihydropyridines (DHP) nifedipine and nitrendipine, implicating voltage-activated Ca channels in the RVD response. Using the fura-2 fluorescence-ratio technique, we observed that cell swelling caused a sustained rise in intracellular Ca ([Ca2+]i) only when [Ca2+]o was normal (1 mM) but not when [Ca2+]o was low (1-10 microM). Furthermore, external Ca was required early on during swelling to induce RVD. If RVD was initially blocked by reducing [Ca2+]o or by addition of verapamil during hypotonic swelling, volume regulation could only be restored by subsequently inducing Ca entry within the first 1 min or less of exposure to hypotonic solution. These data indicate a "calcium window" of less than 1 min, during which RVD is sensitive to Ca, and that part of the Ca-dependent mechanism responsible for achieving RVD undergoes inactivation after swelling. It is concluded that RVD in rabbit PST is modulated by Ca via a DHP-sensitive mechanism in a time dependent manner. PMID- 2260688 TI - Water permeability of apical and basolateral cell membranes of rat inner medullary collecting duct. AB - To quantify the pathways for water permeation through the kidney medulla, knowledge of the water permeability (Posmol) of individual cell membranes in inner medullary collecting duct (IMCD) is required. Therefore IMCD segments from the inner two thirds of inner medulla of Sprague-Dawley rats were perfused in vitro using a setup devised for rapid bath and luminal fluid exchanges (half time, t1/2, of 55 and 41 ms). Differential interference contrast microscopy, coupled to video recording, was used to measure volume and approximate surface areas of single cells. Volume and volume-to-surface area ratio of IMCD cells were strongly correlated with their position along the inner medullary axis. Transmembrane water flow (Jv) was measured in response to a variety of osmotic gradients (delta II) presented on either basolateral or luminal side of the cells. The linear relation between Jv and delta II yielded the cell membrane Posmol, which was then corrected for membrane infoldings. Basolateral membrane Posmol was 126 +/- 3 microns/s. Apical membrane Posmol rose from a basal value of 26 +/- 3 microns/s to 99 +/- 5 microns/s in presence of antidiuretic hormone (ADH). Because of amplification of basolateral membrane, the ADH-stimulated apical membrane remained rate-limiting for transcellular osmotic water flow, and the IMCD cell did not swell significantly. Calculated transcellular Posmol, expressed in terms of smooth luminal surface, was 64 microns/s without ADH and 207 microns/s with ADH. IMCD cells in anisosmotic media displayed almost complete volume regulatory decrease but only partial volume regulatory increase. PMID- 2260689 TI - Hemodynamics, fluid volume, and hormonal responses to chronic high-salt intake in dogs. AB - The sequential hemodynamics, fluid and electrolyte balances, and the hormonal responses to a 7-day high-salt (NaCl) intake were investigated in sodium-depleted conscious dogs (n = 6). Studies were carried out in metabolic cages mounted on sensitive load cells, which enabled continuous 24 h/day monitoring of total body weight (TBW) as an index of changes in body water. Beat-by-beat hemodynamics were determined 24 h/day. Water (700 ml/day iv) intake was maintained constant. Daily fluid and electrolyte balances and hormonal analyses were performed. An increase of daily salt intake from 8 to 120 meq increased TBW 251 +/- 44 g (P less than 0.05), which was sustained thereafter. Average 24-h mean arterial pressure (MAP) and heart rate (HR) remained unchanged. Average cardiac output (CO) increased 11% (P less than 0.05) above control values by day 2, while total peripheral resistance (TPR) decreased proportionally. CO and TPR returned to control values only when low salt was resumed. Blood volume (BV) was unchanged on day 2 as indicated by direct measurement of BV (51Cr-labeled red blood cells) or by analysis of plasma protein concentration. A 92-meq (P less than 0.05) sodium retention was observed initially, and plasma sodium concentration increased slightly. Plasma renin activity, angiotensin II, and aldosterone levels decreased significantly, whereas vasopressin and atrial natriuretic peptide levels remained unchanged. In summary, chronic high-salt intake resulted in a net retention of water and sodium with no changes in MAP, HR, or BV. The rise in CO was offset by a reduction in TPR, which appeared at least in part related to angiotensin II suppression. PMID- 2260690 TI - Ontogeny of adenosine response in guinea pig heart and aorta. AB - Effects of maturation on the responses of isolated perfused hearts and aortic rings to adenosine were examined. Dose-response relationships for adenosine were obtained in aortic rings and hearts isolated from immature (5 days) and mature (1 2 mo) guinea pigs. Immature and mature hearts were perfused at constant flows of 9.9 +/- 0.3 and 9.5 +/- 0.4 ml.min-1.g-1, respectively, and displayed basal resistances of 4.8 +/- 0.1 and 6.7 +/- 0.2 mmHg.ml-1.min.g. Immature hearts were more sensitive to exogenous adenosine, displaying a significantly lower 50% effective concentration (EC50, 2.5 x 10(-8) M) than mature hearts (1.1 x 10(-7) M, P less than 0.05). Adenosine induced dilation at a lower threshold dose in immature hearts (3 x 10(-9) M, 6.0 +/- 0.3% relaxation) than in mature hearts (10(-8) M, 3.1 +/- 1.3% relaxation). The time required to elicit 50% of the observed dilation was similar in immature and mature hearts, yet the time required for basal tone to recover by 50% was approximately 100% greater in immature hearts (P less than 0.05). Immature aortic rings, stretched to their optimal resting tensions and contracted with EC85 doses of prostaglandin F2 alpha, displayed a significantly lower EC50 (7.7 x 10(-5) M) than mature rings (1.1 x 10(-4) M, P less than 0.05). The maximum percent response to adenosine was greater in immature vessels (64 +/- 1 vs. 54 +/- 0.4%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260691 TI - Regional blood flow in transected rat spinal cord during hypothermia. AB - Regional blood flow (RBF) increases in the spinal cord and sciatic nerve of acutely hypothermic rats. To determine whether cord transection affects this response, we measured RBF in rat spinal cord and sciatic nerve 2 h after cord transection at vertebrae T8 (n = 18 rats) and T11 (n = 18 rats) using [14C]butanol distribution. Nine in each group were normothermic controls. In T11 transection-hypothermia (25-27 degrees C rectal temperature), RBF increased in the three rostral cord segments by 28-40% (P less than 0.05); caudally, cord RBF was depressed in two segments (P less than 0.05), unchanged in the other; RBF fell in nerve (P less than 0.05). In T8 transection-hypothermia, RBF was unchanged in the two rostral cord segments; caudally, RBF was depressed in one cord segment (P less than 0.05) and unchanged in the others; RBF was unchanged in nerve. We conclude that RBF does not rise in caudal spinal cord segments or in sciatic nerve during hypothermia in rats with prior spinal cord transection. PMID- 2260692 TI - No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia. AB - Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia. PMID- 2260693 TI - Time course and mechanism of endothelial dysfunction in isolated ischemic- and hypoxic-perfused rat hearts. AB - Isolated perfused rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 2.5, 5, 10, or 20 min and then were tested for responsiveness to the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator nitroglycerin (NTG). ACh relaxation was impaired 2.5 min after reperfusion (32 +/- 3% of initial control, P less than 0.01) and remained comparably depressed at every time thereafter. No significant decrease in vasodilator response to NTG occurred at any time. Endothelial dysfunction was prevented by recombinant human superoxide dismutase (hSOD, 5 mg/heart) but not by the hydroxyl radical scavenger N-(2-mercaptopropionyl) glycine (8 mg/heart). Comparable effects and a similar time course were observed in hypoxic hearts reoxygenated for periods up to 20 min. Chemiluminescence of perfusion effluent employed as an index of free radical production was measured at all postreperfusion times in ischemic hearts. Ischemia alone produced small increases in chemiluminescence. Reperfusion, however, produced significantly higher increases in chemiluminescence, with a large burst of activity at 0.25 min, which was blocked by hSOD. These findings suggest that endothelial dysfunction resulting in decreased release of endothelium-derived relaxing factor occurs very early after reperfusion or reoxygenation and may be due to the action of superoxide free radicals. PMID- 2260694 TI - Hemodynamic and sympathetic effects of spinal administration of neuropeptide Y in rats. AB - Intrathecal administration of 4 nmol/kg neuropeptide Y in Dial-urethane anesthetized rats elicited decreases in arterial pressure, renal sympathetic nerve activity, and a slight decrease in heart rate. The depressor response was associated with a sustained hindquarters and mesenteric vasodilation resulting in a decrease in total peripheral resistance. Intrathecal NPY also resulted in a decrease in renal sympathetic nerve activity. There was a positive correlation between the percent changes in arterial pressure and renal sympathetic nerve activity. With the use of renal nerve activity and heart rate as indexes, NPY resulted in a decrease in baroreflex sensitivity. The depressor effect of intrathecal NPY did not appear to be due to spinal vasoconstriction and ischemia, since spinal microvascular resistance was decreased slightly. We conclude that the intrathecal administration of NPY produces an inhibition of sympathetic nerve activity, resulting in a decrease in total peripheral resistance and arterial pressure. PMID- 2260695 TI - Late-onset renal hypertension in old rats alters myocardial microvessels. AB - We tested the hypothesis that late-onset hypertension in middle-aged (15 mo) and senescent (24 mo) rats would adversely affect the coronary microvasculature. Morphometric analyses were performed on coronary capillaries and arterioles from rats with one-kidney, figure-8 renal wrap hypertension of 3-mo duration. Compared with control rats, wall-to-lumen ratios of arterioles with lumen diameters less than 25 microns were higher in the two hypertensive groups by approximately 30%; larger arterioles did not show consistent intergroup differences. A comparison of the two control groups revealed that wall-to-lumen ratio of arterioles with lumen diameters less than 50 microns tended to be greater in the senescent rats. Capillary numerical density was markedly reduced in the hypertensive animals of both age groups and caused an increase in the mean Krough cylinder radius and in the mean capillary domain. The latter increased by 28-63%; the largest increment occurred in the endomyocardium of the senescent group. A trend toward increased heterogeneity of capillary spacing was also noted in the hypertensive rats. The observed microvascular alterations occurred in the absence of an absolute increase in left ventricular mass but in the presence of cardiocyte hypertrophy. Thus the decrements in capillary numerical density are not only due to inadequate growth but reflect an absolute reduction in the number of these vessels associated with cardiocyte loss. It is concluded that late-onset hypertension in middle-aged and senescent rats is characterized by left ventricular wall remodeling that includes microvascular alterations that would be expected to limit maximal myocardial flow and O2 supply to the cardiocyte. PMID- 2260696 TI - Influence of hemoconcentration on arteriolar oxygen transport in hamster striated muscle. AB - We investigated the influence of isovolemic hemoconcentration on microcirculatory hemodynamics and oxygen transport in the hamster cheek pouch retractor muscle. In 17 hamsters, measurements of red blood cell velocity, hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2), and longitudinal SO2 gradient (delta SO2/L) were made in four branching orders of arterioles before and after isovolemic exchange with packed red blood cells. Hemoconcentration increased systemic hematocrit from 50 to 65%; systemic blood gases were unchanged, but mean arterial blood pressure increased approximately 10 mmHg. Accompanying this change in systemic hematocrit the microcirculatory hematocrit increased from 40 to 50%, and red blood cell velocity and computed blood flow decreased approximately 40 and 30%, respectively. In addition, delta SO2/L was significantly increased in the four arteriolar branching orders compared with control values. We estimated that approximately 10% of the oxygen that diffused across the arteriolar network was consumed by the surrounding tissue with the remainder assumed to have diffused to venules and capillaries. After hemoconcentration, the proportion of this diffusional transfer increased by approximately 80%. Convective oxygen flow remained at its control level in the first-order arterioles and progressively decreased below control in the more distal branching orders. Our analysis of arteriolar oxygen diffusion indicated that tissue oxygenation was unchanged after hemoconcentration, a result that can be attributed to a combined effect of decreased red blood cell velocity, arteriolar vasodilation, increased precapillary oxygen loss, and a relatively modest reduction in convective oxygen flow to the capillaries. PMID- 2260697 TI - Role of adenosine in regulation of regional cerebral blood flow in sensory cortex. AB - We have previously demonstrated that rat pial arterioles located on the somatosensory cortex dilated in response to contralateral sciatic nerve stimulation (SNS). We hypothesized that the vasodilation was mediated by adenosine, released as a result of somatosensory cortex activation. To test this hypothesis, we examined the effects of SNS (0.15-0.2 V, 5 ms, 5 Hz for 20 s) on pial arterioles under conditions of altered adenosine availability. Cerebrospinal fluid (CSF) adenosine was altered by perfusing mock CSF, under a cranial window in anesthetized rats, containing either an adenosine uptake competitor (dipyridamole or inosine) or an adenosine receptor blocker (theophylline). With CSF only, SNS caused pial arterioles (resting diam, 29 +/- 1 micron) to dilate by 38 +/- 10% (peak magnitude) for 32 +/- 2 s. Dipyridamole (10(-6) M) significantly (P less than 0.02) enhanced both the magnitude (to 62 +/- 12%) and duration (to 68 +/- 10 s) of the response. Similarly, inosine (10(-3) M) significantly (P less than 0.02) potentiated the vasodilative response from resting values of 27 +/- 5% and 34.8 +/- 4.1 s to 37 +/- 6% and 89.6 +/- 14.1 s. In contrast, theophylline (5 x 10(-5) M) significantly (P less than 0.001) attenuated arteriolar vasodilation from resting values of 38 +/- 5% and 29.3 +/- 1.2 s to 18 +/- 3% and 22.0 +/- 0.9 s. Neither dipyridamole nor theophylline had a significant effect on neuronal response (sensory-evoked response) recorded from the somatosensory cortex. These results suggest that adenosine is involved in the regulation of pial vasodilation during cerebral cortical activation. PMID- 2260698 TI - Effects of neuropeptide Y on regulation of blood flow rate in canine myocardium. AB - The effect of neuropeptide Y (NPY) on tension development was examined in isolated canine coronary arteries, and the effects on local myocardial blood flow rate were studied in open-chest anesthetized dogs by the local 133Xe washout technique. By immunohistochemistry, numerous NPY-like immunoreactive nerve fibers were identified in the adventitia of canine coronary arteries. NPY (10(-9)-10(-6) M) supplied to isolated epicardial segments of the left anterior descending coronary artery induced a modest vasoconstriction, with a maximum tension of 0.95 mN, that was only 6.9% of the response to K+. In contrast, intracoronary NPY (0.01-10 micrograms) induced a considerable degree of vasoconstriction; the reduction of blood flow rate was dose related, with a maximum reduction to 52% of control values. The effect of intracoronary NPY (1 microgram) on maximally relaxed arterioles elicited by 30 s of ischemia was studied in separate experiments during reactive hyperemia. NPY induced a decrease in maximum blood flow during reactive hyperemia (166.6 vs. 214.6% of preocclusive blood flow rate, mean values; P = 0.05), an increase in the cumulative excess blood flow (61.0 vs. 35.3 ml/100 g; P = 0.02), and an increase in the duration of reactive hyperemia compared with control values (66 vs. 41 s; P = 0.02). Thus we conclude that in the heart NPY is a potent vasoconstrictor that seems to act preferentially on smaller intramyocardial arterioles. Furthermore, NPY inhibits vascular relaxation of myocardial resistance vessels after ischemia, suggesting that this peptide may participate in the regulation of myocardial blood flow not only during physiological conditions but also after ischemia. PMID- 2260699 TI - Direct electrophysiological actions of pentobarbital at concentrations achieved during general anesthesia. AB - Pentobarbital and alpha-chloralose are widely used for experimental anesthesia, but their direct electrophysiological actions at anesthetic concentrations are unknown. Trough and peak concentrations measured by high-performance liquid chromatography averaged 27 +/- 3 and 45 +/- 13 mg/l (means +/- SD) for pentobarbital and 41 +/- 15 and 103 +/- 13 mg/l for alpha-chloralose in dogs receiving them for general anesthesia. The direct effects of each agent on papillary muscle action potentials obtained from guinea pigs killed by decapitation were studied in vitro. Pentobarbital increased action potential duration to 95% by 24 +/- 6 and 33 +/- 4% at 25 and 50 mg/l (P less than 0.001 for each), respectively, and caused corresponding increases in effective refractory period. Furthermore, pentobarbital reduced maximum rate of voltage change (Vmax) of phase 0 in a voltage-, rate-, and concentration-dependent fashion, suggesting use-dependent sodium channel blocking actions. The voltage dependence of Vmax was shifted by 3.7 +/- 1.7 (P less than 0.01) and 6.5 +/- 1.8 mV (P less than 0.001) by 25 and 50 mg/l pentobarbital, respectively. In canine ventricular muscle, pentobarbital caused rate- and concentration-dependent decreases in Vmax and increases in action potential duration and refractory period over a concentration range of 5-100 mg/l. alpha-Chloralose was devoid of direct electrophysiological effects in both species. We conclude that pentobarbital has potentially important electrophysiological actions on ventricular tissues at concentrations required for general anesthesia and may confound the results of in vivo studies. PMID- 2260700 TI - Central angiotensinergic system and hypertonic resuscitation from severe hemorrhage. AB - Single injections of 4 ml/kg hypertonic NaCl (7.5%) resuscitate dogs from severe blood loss (40-45 ml/kg). Mechanisms involve osmolarity-dependent volume expansion, increased myocardial contractility, and vasodilation. The role of central angiotensinergic pathways in the hemorrhage-hypertonic resuscitation interaction was investigated through experiments performed on male pentobarbital sodium-anesthetized dogs bled to, and held at, 40 mmHg for 30 min. Dogs were treated with 4 ml/kg of 7.5% NaCl or 32 of 0.9% NaCl iv preceded by intracerebroventricular (ICV) injections of 150 micrograms saralasin, 20 micrograms arginine vasopressin inhibitor (AVPI), or 10 micrograms morphine. ICV saralasin and morphine inhibited the full recovery response to hypertonic NaCl, whereas AVPI had no such effect. Saralasin did not inhibit the recovery from hemorrhagic shock produced by large volume isotonic saline reexpansion. These data demonstrate an interaction between the central angiotensin system and small volume hypertonic resuscitation from severe hemorrhagic shock but not between this central system and large volume isotonic reexpansion of circulatory volume. In contrast, the central vasopressinergic system does not appear to be similarly involved. PMID- 2260701 TI - 23Na-NMR measurements of intracellular sodium in intact perfused ferret hearts during ischemia and reperfusion. AB - 23Na nuclear magnetic resonance (NMR) spectroscopy was utilized to measure intracellular Na+ in perfused ferret hearts exposed to the shift reagent dysprosium triethylenetramine-hexa-acetic acid [Dy(TTHA)3-]. The intracellular Na+ signal was small under normal perfusion conditions; resolution was enhanced by using a Jump-Return NMR pulse protocol. During 20 min of total global ischemia at 30 degrees C, intracellular Na+ concentration ([Na+]i) increased steadily to a peak value fivefold greater than control. [Na+]i declined monotonically back to control levels within 9 min of reperfusion. In contrast, the mean contractile pressure only recovered to 54% of control levels. Thus major alterations in Na+ homeostasis occur during severe ischemia. [Na+] recovers rapidly during reperfusion and is therefore dissociated from the lingering postischemic depression of contractile function known as "stunning." PMID- 2260702 TI - Heart and brain nucleotide pools during hemorrhage and resuscitation. AB - Sequential 31P nuclear magnetic resonance (NMR) spectra were measured in adult dogs to determine the relationship between cardiac function and myocardial intracellular pH (pHi) and phosphorylated energy metabolites during 2 h of hemorrhagic shock. Simultaneous measurements of coronary blood flow (radioactive microspheres), arterial and coronary sinus pH, blood gases, and oxygen content were performed. In addition, changes in brain NMR spectra were correlated with changes in cerebral blood flow during shock. Two hurs of hypovolemic shock resulted in significant decreases in phosphocreatine (PCr), PCr-to-ATP ratio, and pHi, whereas Pi rose significantly relative to baseline values. Return of shed blood and crystalloid fluid resuscitation improved cerebral and coronary perfusion and returned cardiac contractile function to near baseline values. We conclude that severe and sustained hemorrhagic shock produced significant alterations in brain and heart phosphorylated metabolites as well as significant intracellular acidosis; however, these changes in energy metabolites were reversible with adequate fluid resuscitation from shock. PMID- 2260703 TI - Vascular mechanics of venous drainage in dog hindlimbs. AB - The time constant of venous drainage (tau v) of a vascular bed is an important determinant of the change in regional volume that will occur with a change in blood flow or venous pressure (Pv). Therefore, to measure tau v of the dog hindlimb, the vasculature was isolated and perfused with a pump. Inflow and outflow were measured with electromagnetic flow probes. Blood volume was changed (delta V) by changing flow (delta Q), and a double-occlusion procedure was used to obtain the venous elastic recoil pressure (Pel) from the plateau of Pv. Venous resistance (Rv), compliance (Cv), and tau v could then be calculated. Rv was 7.7 +/- 1.4 mmHg.ml-1.min.100 g-1 and Cv was 0.59 +/- 0.25 ml/mmHg, tau v calculated from the product of Rv and Cv was 4.20 +/- 1.58 s and from the ratio of delta V to delta Q was 4.95 +/- 1.53 s (P = NS) at a mean Pel of 17.6 +/- 3.7 mmHg. delta V was also produced by changing Pv; the average tau v (1.95 +/- 0.37 s), was shorter than that with changes in flow. Finally, a ramp increase in flow was used to calculate tau v from the time delay between inflow and outflow. tau v by this method was longer (6.06 +/- 1.70 s) and was probably influenced by the change in Pv. In conclusion, the hindlimb has a short tau v of venous drainage and would not be expected to store large volumes of blood even with large increases in blood flow. PMID- 2260704 TI - Skin vascular bed is a potential blood reservoir during heat stress. AB - To determine the potential role of the skin vasculature as a blood reservoir, we measured venous compliance (Cv), resistance (Rv), and their product, the time constant of venous drainage (tau sk = RvCv), in skin flaps from the hindlimbs of 15 dogs anesthetized with pentobarbital sodium at different core temperatures (Tc, 37-42 degrees C), skin temperature (Ts, 25.3-50.0 degrees C), and during an infusion of papaverine (5%). The vasculature of the flap was isolated, and a double-occlusion technique was used to measure the static pressure in the venous compartment. The blood volume of the flap was altered by changing either flow or outflow pressure (Pv). The change in volume was estimated from the change in weight of the flap with a force transducer. At Tc = 37 degrees C, Rv was 2.27 +/- 0.81 mmHg.min.ml-1.100 g-1 (means +/- SD), Cv was 0.17 +/- 0.06 ml.mmHg-1.100 g 1, and tau sk was 28.0 +/- 8.8 s. Rv decreased with elevated Tc, Ts, and with papaverine. Cv increased with a rise in Tc and Ts. Increasing Tc and Ts did not change tau sk, but the papaverine infusion shortened it. The lowest tau sk (20 s) occurred during maximal vasodilatation. This long tau sk indicates that the skin could serve as a blood reservoir during heat stress. PMID- 2260705 TI - Neutrophils accumulate and contribute to skeletal muscle dysfunction after ischemia-reperfusion. AB - Skeletal muscles subjected to ischemia and then reperfusion develop contractile dysfunction for reasons that are unclear. We found that rats pretreated with vinblastine 4 days before study had decreased numbers of blood neutrophils and increased gastrocnemius muscle function after ischemia (3h) and reperfusion (4 h) compared with untreated rats or rats treated 4 days before study with saline. By comparison, rats pretreated with vinblastine or saline 1 day before study had increased blood neutrophils and decreased gastrocnemius muscle contractile function after ischemia-reperfusion compared with untreated rats. In addition, numbers of neutrophils in gastrocnemius muscles paralleled numbers of blood neutrophils and correlated with gastrocnemius muscle edema and contractile function after ischemia and reperfusion. The results indicate that neutrophils accumulate and may play an important role in the genesis of skeletal muscle contractile dysfunction after ischemia-reperfusion. PMID- 2260706 TI - Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning. AB - It is currently unknown how preconditioning the heart with brief periods of ischemia makes it resistant to infarction from a subsequent ischemic insult. The protein synthesis inhibitors, cycloheximide and actinomycin D, were used to determine whether preconditioning involves synthesis of a protective protein. Ischemia was produced by occlusion of a branch of the left coronary artery in open-chest anesthetized rabbits. All groups were subjected to 30 min of ischemia followed by 3 h of reperfusion. The first two groups served as noninhibited controls. Group 1 was subjected to ischemia with no preconditioning. Group 2 was preconditioned with two 5-min ischemic periods each followed by 10 min of reperfusion, before the 30-min ischemic period. Groups 3 and 4 were the same as groups 1 and 2, respectively, except that cycloheximide was administered before coronary occlusion. Groups 5 and 6 were also the same as groups 1 and 2 except that actinomycin D was administered before coronary occlusion. After 3 h of reperfusion all hearts were removed and the size of the ischemic zone and infarct were determined. The percent of the ischemic zone infarcted was small and similar in all preconditioned groups (3.3 +/- 1.1% for group 2, 7.4 +/- 3.3% for group 4, and 0.5 +/- 0.7% for group 6). All nonpreconditioned groups had large infarcts with no differences between groups (39.0 +/- 8.5% for group 1, 31.6 +/- 6.3% for group 3, 30.8 +/- 5.9% for group 5). Because neither cycloheximide nor actinomycin D could block protection afforded by preconditioning, it seems unlikely that synthesis of a protective protein is the mechanism of protection. PMID- 2260707 TI - Vasodilation induced by endothelin: role of EDRF and prostanoids in rat hindquarters. AB - Hemodynamic responses to endothelin (ET-1) were studied in hindquarters of anesthetized rats and also in isolated buffer-perfused hindquarters of pithed rats. ET-1 (10-100 pmol ia) produced brief dose-related increases in hindquarter blood flow. Acetylcholine (ACh. 0.3-1 micrograms ia) produced similar vasodilator responses. Hemodynamic responses elicited by either ET-1 or ACh were not significantly altered by pretreatment with indomethacin. ET-1 produced dose dependent increases in skeletal muscle microvascular perfusion, whereas ET-1 had no effect on cutaneous microvascular perfusion, suggesting that vasodilation in the skeletal muscle of the hindlimb contributes to the increase in hindquarter blood flow induced by ET-1. Hemodynamic effects of ET-1 and ACh were studied in the isolated in situ buffer-perfused hindquarters of pithed rats. ET-1 (0.01-300 pmol ia) produced only dose-dependent increases in hindquarter perfusion pressure under basal conditions or when the vascular preparation was precontracted with methoxamine. ET-1 induced vasorelaxation was not observed. ACh (3 microgram ia) produced a 64% reduction in hindquarter perfusion pressure; indicative of endothelium-dependent relaxation. ET-3 (0.1-300 pmol) produced only dose dependent increases in hindquarter perfusion pressure. When hemodynamic effects of ET-1 were studied under conditions of constant pressure, results were similar to those obtained under constant flow. This study demonstrates that in the rat hindquarters endothelium-derived relaxing factors and prostanoids do not appear to be mediators of endothelin-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260708 TI - Effects of extracellular Mg2+ on T- and L-type Ca2+ currents in single atrial myocytes. AB - Whole cell voltage-clamp techniques were used to study the effects of extracellular Mg2+ on T- and L-type Ca2+ currents recorded from single atrial myocytes from cat heart. T and L currents were distinguished primarily by their voltage dependence. With 5.4 mM Ca2+ as charge carrier, maximal T- and L-current densities were 1.0 +/- 0.06 and 9.7 +/- 0.4 pA/pF, respectively. Nickel (Ni2+, 50 microM) inhibited maximal T current (-65.6 +/- 5.9%) more than L current (-15.7 +/- 2.4%), and 10 microM cadmium (Cd2+) inhibited L current (-65.5 +/- 5.9%) without significant effect on T current (-8.7 +/- 8.1%). Mg2+ elicited a dose dependent inhibition of both T and L currents. Mg2+ less than 8.4 mM inhibited T current more than L current. At Mg2+ greater than or equal to 8.4 mM, T-current inhibition reach a plateau at approximately 52%, whereas L current was further inhibited (-65%) at 16.8 mM Mg2+. Mg2+ elicited a dose-dependent positive shift in half-maximal voltages of activation and inactivation for both T and L currents. Mg2(+)-induced inhibition of both T and L currents was greater in lower (2.7 mM) external Ca2+. Finally, 4.2 mM Mg2+ and 50 microM Ni2+ elicited a similar decrease in the late diastolic slope of subsidiary pacemaker action potentials, whereas 10 microM Cd2+ markedly inhibited action potential amplitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260709 TI - Intracellular calcium and high-energy phosphates in isolated cardiac myocytes. AB - The relationship between intracellular calcium (Cai) and high-energy phosphates was studied in adult cardiac myocytes. Cai and high-energy phosphates were measured in the same population of cells. Cai, reported by the fluorescence of fura-2, was maintained at normal levels in the presence of increased transsarcolemmal calcium gradients, up to 5 mM extracellular calcium concentration. Cai was experimentally elevated by increasing calcium influx from the extracellular medium and/or by diminishing calcium efflux by Na-Ca exchange. Under these conditions, cells contracted and relengthened repetitively. The regulation of high-energy phosphates was challenged by increasing ATP utilization and by inhibiting ATP synthesis. Cai regulation was not affected by inhibition of glycolysis or NADH oxidation, so long as ATP concentration remained unchanged. High-energy phosphates were not depleted in beating cells with intact NADH oxidation, but inhibition of NADH oxidation caused a significant drop in phosphocreatine, demonstrating the increased rate of ATP consumption during beating. In beating cells, as in the working heart, ATP supply is increased to meet ATP demand, and steady-state ATP and phosphocreatine concentrations remain unchanged. PMID- 2260710 TI - Effects of skeletal muscle fiber deformation on lymphatic volumes. AB - Because lymphatics in skeletal muscle have no smooth muscle, they are expanded and compressed solely by stresses in the surrounding tissue. Whole organ experiments have indicated that lymph flow is significantly elevated during muscle activity, yet the underlying mechanism for lymph formation has not been identified. To investigate this mechanism, specimens of the rat spinotrapezius muscle were fixed in situ at the undeformed in vivo length, and also in the stretched and contracted states, for histological examination. Cross-sectional areas of lymphatic vessels, skeletal muscle fibers, blood vessels, and interstitial space were measured using a stereological technique. The in situ preparation with intact muscle fascia was essential for preservation of interstitial volume. The lymphatic cross-sectional areas and muscle stretch ratios from 20 rats showed that lymphatic volume increased by 57% for a 20% stretch, and decreased by 45% for a 20% contraction. Deformation of the incompressible muscle fibers appears to inversely affect surrounding tissue structures; e.g., decreased fiber cross-sectional area during stretch increases interstitial spacing between fibers, which in turn expands lymphatics. PMID- 2260711 TI - Effect of wall stretch on coronary hemodynamics in isolated canine interventricular septum. AB - The effects of stretch on coronary pressure-flow relations are not well understood. To examine the role of wall stretch per se on coronary hemodynamics, we studied arterially perfused isolated canine interventricular septa in a noncontracting state with vasodilated vessels. We compared the hemodynamic parameters of zero-flow pressure and resistance during passive stretching in the circumferential and the base-to-apex directions alone as well as during simultaneous biaxial stretching in both directions. Even in the unloaded state the zero-flow pressure was positive. Any type of stretching significantly increased the zero-flow pressure and the resistance from their unloaded values. The pressure-flow responses also showed directional dependence. When stretches with matched strains or stresses in each direction were applied sequentially, the resistance increases corresponded to the direction of higher stress. Conversely, the zero-flow pressure response increase corresponded to the direction of greater strain. However, neither response correlated with a measure of global tissue stiffness. Thus there is a complex and tight mechanical interaction between the vessels and the surrounding tissue. These interactions, but not the tissue stiffness, are important determinants of coronary pressure-flow responses during stretch. PMID- 2260712 TI - Lanthanum blocks a specific component of IK and screens membrane surface change in cardiac cells. AB - Delayed rectifier outward K+ current (IK) in guinea pig ventricular myocytes represents the sum of two currents: a slowly activating delayed rectifier K+ current (IK.s) and a relatively rapidly activating delayed rectifier K+ current (IK.r), which rectifies at positive potentials and is specifically blocked by the class III antiarrhythmic agent, E-4031. La3+ was previously reported to block an unidentified component of IK in these cells. We used the whole cell voltage-clamp technique on isolated myocytes and confirmed these results: we show that the current blocked by La3+ (greater than or equal to 1 microM) is IK.r. This block is not caused by La3+ displacement of surface-bound Ca2+. Thus, in the presence of either E-4031 or La3+, IK represents the activation of a single current, IK.s. La3+ (10 microM-1 mM) also caused a positive shift in the voltage dependence of the activation curve of IK.s. When we assumed that La3+ acts to bind and screen negative surface charges on the outer sarcolemmal membrane, the external surface potential of these cells (in 1.8 mM Ca2+) could be estimated to be -19 mV. A modification of the Gouy-Chapman equation was used to estimate the equilibrium constant for La3+ binding (10.7 mM-1) and the minimum spacing between the negative charges on the surface membrane (22 A). PMID- 2260713 TI - Myogenic responses of isolated arterioles: test for a rate-sensitive mechanism. AB - The arterial myogenic response may consist of both static- and rate-sensitive components. However, in a recent study of bat wing arterioles, we were unable to demonstrate rate-sensitive constrictions when luminal pressure was elevated at rates between 0.06 and 1 mmHg/s. We have now examined this response in isolated arterioles in vitro, where pressure could be elevated more rapidly. Arterioles were dissected from the hamster cheek pouch and cannulated with micropipettes. Diameters were measured using an inverted microscope and video system, while the vessels were pressurized at various rates (up to 120 cmH2O/s) without flow. Most arterioles developed spontaneous tone and vasomotion and showed myogenic responses over the pressure range 40-160 cmH2O. The magnitude and time course of the active diameter response to a rapid pressure change was highly dependent on the amplitude and direction of the pressure step; monophasic constrictions were observed in response to small-amplitude, positive-pressure steps, and biphasic constrictions were consistently observed when box pressure was elevated to values exceeding 120 cmH2O. The time courses of these responses could be partially, but not completely, explained by a myogenic mechanism with static- and rate-sensitive components. The possible mechanism and physiological significance of this behavior in a microvascular network are discussed. PMID- 2260714 TI - Iron-mediated radical reactions upon reperfusion contribute to myocardial "stunning". AB - Recent evidence suggests that postischemic myocardial dysfunction ("stunning") is mediated by iron-catalyzed free radical reactions, but the exact time window during which the critical iron-mediated damage develops remains unknown. Furthermore, the evidence that iron promotes free radical reactions in vivo is indirect. Thus open-chest dogs undergoing a 15-min coronary occlusion and 4 h of reperfusion were given one of the following intracoronary infusions: desferrioxamine (DF) beginning 2 min before reperfusion (group I), DF beginning 1 min after reperfusion (group II), iron-loaded DF in dosage identical to group I (group III), or vehicle (controls, group IV). Recovery of contractile function was substantially greater in group I than in controls, whereas in groups II and III it was indistinguishable from controls. To determine whether the protection afforded by DF was due to inhibition of free radical reactions, myocardial production of free radicals was directly assessed by intracoronary infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). In controls (group VI), radical adducts of PBN were released in the coronary venous blood after reperfusion. DF given as in group I (group V) markedly suppressed myocardial production of PBN adducts. These results strongly suggest that a substantial portion of the damage responsible for myocardial stunning is caused by iron catalyzed free radical reactions that develop in the initial seconds of reperfusion and can be prevented by administration of iron chelators started just before reflow. Furthermore, the results demonstrate that attenuation of postischemic dysfunction by DF is associated with attenuation of free radical reactions in vivo, thereby providing direct evidence for a pathogenetic role of iron-catalyzed free radical reactions in myocardial stunning in the intact animal. PMID- 2260715 TI - Determination of microvascular oxyhemoglobin saturations using cryospectrophotometry. AB - Although a four-wavelength method for cryospectrophotometric measurement of intravascular oxyhemoglobin (HbO2) saturations has previously been described, the relationship between experimental measurements and theory has not been clearly detailed. The current work utilizes an empirical relationship between HbO2 saturation measurements and reflected light oximetry, which is consistent with the two-flux theory of Kubelka and Munk (Z. Tech. Phys. 11a: 593-603, 1931). To obtain linear, concentration-independent calibration curves, the theoretical results require that 1) the complex function relating optical density, scattering, and absorption can be linearly approximated over the range of scattering and absorption coefficients used; and 2) the scattering coefficient is independent of wavelength. Incident light cannot easily be measured using reflection spectroscopy, which precludes the determination of isosbestic points. Therefore, equibestic wave-length pairs were used at which optical density differences were invariant with saturation. This allows numerous wavelength sets over the range 540-600 nm to be selected, rather than the limited choices of isosbestic wavelengths. Finally, the effects of freeze rate, freeze depth, Hb concentration, and vessel diameter are each discussed in terms of their influence on experimental measurements. PMID- 2260716 TI - Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth. AB - To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260717 TI - Endothelin release is inhibited by coculture of endothelial cells with cells of vascular media. AB - Endothelin is a potent vasoconstrictor peptide and a smooth muscle mitogen produced in large amounts by endothelial cells in culture. To determine whether other cellular elements of the vessel wall modify the release or clearance of endothelin, we studied the effect of coculture of endothelial cells with vascular smooth muscle cells or fibroblasts on endothelin release. Endothelial cells were grown to confluence on microcarrier beads and transferred to dishes containing confluent cultures of smooth muscle cells or fibroblasts or control media only. In parallel experiments, endothelial cells on microcarrier beads were incubated in media conditioned by 48-h exposure to smooth muscle cells or fibroblasts. Endothelin concentration was determined by radioimmunoassay (rabbit anti endothelin-1 serum). Endothelial cells alone released large amounts of endothelin: 169 +/- 60 and 982 +/- 237 pg/10(6) endothelial cells at 4 and 24 h, respectively. Endothelin accumulation was markedly reduced in coculture with smooth muscle cells or fibroblasts by 81 +/- 10 and 49 +/- 5% (P less than 0.05), respectively, at 24 h. This difference could not be explained by smooth muscle cell binding or degradation of endothelin. Furthermore, smooth muscle cell- or fibroblast-conditioned media significantly reduced endothelin release, and twofold concentration of smooth muscle cell-conditioned media fully reproduced the inhibition of endothelin release found in coculture, confirming the presence of a transferable inhibitor. Therefore, we propose that endothelin secretion from endothelial cells may be regulated by an inhibitory factor produced by the vascular media. This mechanism might limit the production of endothelin in intact vessels and thereby protect against excessive vasoconstriction or proliferation of vascular target cells. PMID- 2260718 TI - Myocardial modulation of coronary circulation. PMID- 2260719 TI - Obese and lean Zucker rats differ in preferences for sham-fed corn oil or sucrose. AB - Obese Zucker rats show greater preference for fatty foods in dietary selection studies than do lean rats. We wished to evaluate the preference for dietary fats in Zucker rats in the absence of postingestive cues. Zucker rats (6 lean and 6 obese) were fitted with gastric cannulas for sham feeding. All sham-feeding tests lasted for 30 min. On training days, rats were sham fed 100% corn oil or, on alternate days, rats were sham fed various concentrations of sucrose in volumes yoked to intakes of corn oil. On preference test days, rats were offered 100% corn oil and one sucrose concentration simultaneously for sham feeding. During preference tests, obese rats preferred 100% corn oil to 10% sucrose, whereas lean rats preferred 10% sucrose to 100% corn oil. Obese rats equally preferred 17.5% sucrose and 100% corn oil, whereas lean Zucker rats equally preferred 2.5% sucrose and 100% corn oil. When sucrose concentration was increased to 20% both obese and lean Zucker rats preferred sucrose to 100% corn oil. These results combined with our previously reported results showing that intraduodenally administered fats do not differ in satiating potency for obese and lean Zucker rats (6) strongly suggest that the preference of obese rats for fatty foods is largely mediated by orosensory mechanisms. PMID- 2260720 TI - Effect of weight cycling on susceptibility to dietary obesity. AB - Weight cycling, defined as repeated episodes of weight loss followed by weight regain, has been suggested to make rats more energy efficient and produce a state of energy balance favoring accumulation of excess body fat. In addition, weight cycling may favor accumulation of fat in central vs. peripheral adipose depots. In the present study, we gave two groups of female Wistar rats ad libitum access to an obesity-producing high-fat diet (60% of calories from fat). Both groups had previously eaten a low-fat stock diet, but one group had been subjected to three bouts of weight cycling. Rats that were previously weight cycled gained less body weight and body fat when given the high-fat diet than did controls. The lower rate of weight gain was due to a lesser increase in food intake, since daily energy expenditure was significantly lower in previously cycled rats than in controls. In summary, weight cycling does not appear to predispose rats to becoming obese on a high-calorie diet and apparently produces some effect on food intake that reduces, at least in the short run, weight gain on the high-calorie diet. PMID- 2260721 TI - Metabolic differences between obesity-prone and obesity-resistant rats. AB - We compared, across several physiological variables, rats most and least susceptible to develop obesity when given a high-fat diet. After 4 wk of eating a high-fat diet (60% of calories from fat), rats in the upper (obesity prone, OP) and lower (obesity resistant, OR) quartiles for weight gain were further studied. OP rats ate significantly more than OR rats, but this did not completely explain differences in their susceptibility to dietary obesity. No differences in 24-h energy expenditure were found between groups. OR rats had a significantly lower 24-h respiratory quotient, indicative of a greater relative proportion of fat oxidation and lower plasma levels of free fatty acids (FFA) than OP rats. Thus the ability to avoid dietary obesity produced by a high-fat diet may depend on an ability to increase fat oxidation in response to increased fat intake. Insulin sensitivity, measured by a euglycemic insulin clamp, was significantly higher in OR than OP rats. We cannot determine from these data whether insulin resistance developed as a consequence of elevated FFA levels or whether the ability to oxidize FFA declined as a result of development of insulin resistance. In summary, we propose that rats able to resist becoming obese on a high-fat diet have the ability to adjust the composition of fuel oxidized to the fuel composition of the diet with a minimum increase in body fat. The specific mechanisms by which this occurs are unknown but may be related to effects of diet on insulin sensitivity. PMID- 2260722 TI - Model of spontaneous obesity in aging male Wistar rats. AB - We analyzed retrospectively data from 148 chow-fed male Wistar rats killed between the age of 6 wk and 2 yr while varying in body weight from 136 to 917 g. The purpose of this study was to clarify the relationship of body weight and body lipid content with the composition and cellularity of the epididymal and retroperitoneal fat depots. A positive linear association was found between body weight and body water or fat-free dry residue, whereas total body lipid exhibited a curvilinear relationship with body weight. The weight of the epididymal pads was linearly related to body weight but not to body lipid. In contrast, retroperitoneal pad weight was exponentially related to body weight and paralleled total body lipid. A strong linear correlation was found between total body lipid and weight (r = 0.959) or depot lipid content (r = 0.967) of the retroperitoneal fat pads. In this rat model of aging and spontaneous obesity, significant regional differences exist in adipose depot composition and cellularity. A practical outcome of this study is a simple and accurate prediction of body lipid content from the gravimetric determination of the retroperitoneal fat depots. PMID- 2260723 TI - Fetal catecholamine responses to maternal hypoglycemia. AB - The present studies were designed to determine the fetal catecholamine and metabolic responses to insulin-induced maternal hypoglycemia. Maternal hypoglycemia was induced by a primed constant infusion of insulin and glucose administered to pregnant ewes to maintain maternal glucose at 20-25 mg/dl. Maternal and fetal samples for measurement of catecholamine, glucose, and free fatty acid levels and arterial blood gas analysis were collected before insulin infusion and at intervals thereafter for 6 h. Maternal and fetal plasma catecholamine levels increased significantly in response to hypoglycemia (analysis of variance, P less than 0.01). Fetal insulin and glucagon levels did not change despite a 50% reduction in fetal whole blood glucose concentration. Fetal free fatty acid levels increased significantly during hypoglycemia (P less than 0.05). There were no significant changes in maternal or fetal heart rate, blood pressure, or arterial blood gases during hypoglycemia. These results suggest that the fetus is capable of responding to hypoglycemia with an increase in catecholamine and free fatty acid levels. These results are consistent with the interpretation that the fetus is able to mobilize alternative energy substrates in response to maternal insulin-induced hypoglycemia. PMID- 2260724 TI - Microvascular specializations promoting rapid interstitial solute dispersion in nucleus tractus solitarius. AB - Nucleus tractus solitarius (NTS), an aggregate of several individual nuclear groups in the dorsal medulla oblongata, is involved in virtually all autonomic functions as the first synaptic site in the brain for many peripheral viscerosomatic inputs. We found morphological evidence that dorsocaudal subregions of rat NTS (approximately 800 microns caudal from obex) had fenestrated capillaries and enlarged Virchow-Robin (perivascular) spaces that were similar to those in area postrema but unlike capillaries elsewhere in the medulla oblongata. Complexes of microvessels, consisting of up to 10 small vessels with smooth muscle layers (luminal diameters of 10-45 microns) and several capillaries (average luminal diameter of 4.5 microns), were located in the dorsal midline of NTS within large Virchow-Robin spaces measuring some 2,000 microns 2 in area. In physiological studies, we determined that most of NTS had a definable blood-brain barrier [permeability-surface area (PS) products for a neutral amino acid near 0], but medial and lateral aspects of the commissural subnucleus of NTS had PS products of 16-63 microliters.g-1.min-1 for alpha [14C]aminoisobutyric acid 12 s after intravenous injection. Microvascular differentiations permitting such brisk tracer influx from blood resemble those of area postrema and appear to afford the rich neuropil of commissural NTS with a constant stream of blood-borne information for expediting its regulation of viscerosensory and autonomic functions. PMID- 2260725 TI - Identification of candidate genes for a factor regulating body weight in primates. AB - A weight gain of 20-30% above baseline, induced by gastrostomy overfeeding of subhuman primates or gavage overfeeding of rats, was found to completely suppress voluntary food consumption. When overfeeding was discontinued, body weight and oral intake returned in a coordinated fashion to baseline or "set point" values. This regulatory response could have been due to a circulating peptide that was secreted by adipocytes in proportion to the total body energy store and that mediated satiety at the level of the central nervous system. To search for this factor, a subtractive cDNA cloning strategy was developed, permitting the isolation of primate adipocyte genes with augmented expression in the overfed state. A 1.8-kb cDNA clone prepared by subtraction was found to hybridize to a 5 kb message expressed preferentially in the adipose tissue of overfed macaques and rats. This message, which was restricted in distribution among nonadipose tissues, was also detected in human subcutaneous fat. Candidate genes for satiety factors identified by this approach could be used in further studies of body weight regulation and obesity. PMID- 2260726 TI - Cardiovascular and sensory responses to forearm ischemia and dynamic hand exercise. AB - The relationship between cardiovascular responses and pain produced by the submaximal-effort tourniquet procedure was evaluated in healthy humans. Graded increases in ischemic pain were associated with graded elevations in arterial blood pressure, forearm vascular resistance, and venous tone. Many of the vascular responses to muscle ischemia were typical of the cardiovascular components of the defense reaction and correlated with both the sensory and affective aspects of ischemic pain. The cardiovascular responses to arm ischemia were distinguishable from those produced by rhythmic hand exercise used to produce ischemia. Dynamic hand exercise produced a transient increase in arterial blood pressure, heart rate, and measures of hand discomfort. These responses were enhanced when dynamic hand exercise was conducted under ischemic conditions. The tightly coupled and coordinated cardiovascular responses elicited by ischemic pain represent integrated adaptive responses to painful stimulation. PMID- 2260727 TI - Alteration of baroreflex control of forearm vascular resistance by dietary fatty acids. AB - The effects of dietary safflower (control, n = 10), borage (n = 9), and fish oil (n = 10), as sources of linoleic, gamma-linolenic, and eicosapentaenoic acid, respectively, at a dose of 4.5 ml/day for 4 wk, on cardiovascular responses to lower body negative pressure (LBNP) were studied in normotensive humans in a randomized, double-blind design. Pre- and postsupplementation, subjects were exposed to 5 min of -10 and -40 mmHg LBNP. Blood pressure (BP), heart rate (HR), forearm blood flow (FBF), forearm vascular resistance (FVR), and plasma norepinephrine (PNE) were measured at each level. Subjects were then exposed to a cold-pressor test, isometric handgrip, and forearm ischemia. At pretest, LBNP reduced BP and FBF and increased HR and FVR in all groups. After diets, the PNE and vasoconstrictor responses to -40 mmHg LBNP, as well as the reflex vasodilation on its cessation, were significantly augmented by borage oil. No diet differences were observed in the HR responses to LBNP or in the responses to the other tasks, with the exception that fish oil increased FBF after forearm ischemia. These data indicate that borage oil augments the arterial baroreflex control of vascular resistance. The vasodilatory effects of fish oil may be mediated via local mechanisms. PMID- 2260728 TI - Normalization of arterial pressure after barodenervation: role of pressure natriuresis. AB - Studies in several species have demonstrated that mean arterial pressure (MAP) is normal or only slightly elevated after chronic arterial baroreceptor denervation. We hypothesized that the absence of sustained hypertension after barodenervation was the result of a pressure natriuresis response, secondary to sympathetic vasoconstriction of nonrenal vasculature. To test this hypothesis, MAP, sodium balance (NaBal), and water balance were measured before and after aortic baroreceptor denervation (ABD), sinoaortic denervation (SAD), or sham surgery in conscious rats. MAP was increased 20.0 +/- 3.7 mmHg 1 day after ABD but returned to control by day 3. ABD had no significant effect on daily NaBal or water balance. The responses to SAD were similar to those after ABD, with the exception that a significant natriuresis was observed the first day after SAD. However, this was followed by a significant antinatriuresis on day 2, when MAP was still elevated. By day 3 after SAD, MAP, NaBal, and water balance were not significantly different from control. These results suggest that the normalization of MAP after ABD or SAD is not the result of pressure natriuresis but rather failure to maintain a chronic elevation of sympathetic activity after barodenervation. PMID- 2260729 TI - Entrainment of circadian rhythms with 26-h bright light and sleep-wake schedules. AB - Subjects followed a 26-h sleep-wake schedule and were exposed to various light patterns while living at home exposed to the conflicting 24-h zeitgebers. In one protocol, a 26-h light pattern containing evening bright light was compared with a natural-light-only pattern. In another protocol, the evening-light pattern was compared with a morning-light pattern. Rectal temperature was continuously measured. Sleep times were estimated from daily sleep logs. The sleep times of most subjects conformed fairly well to the 26-h sleep-wake schedule, although the evening-light condition produced slightly better results. A larger proportion of subjects had their temperature rhythm entrained to the 26-h schedule during the evening-light condition than during the morning-light or natural-light conditions. Entrainment to the 26-h schedule was achieved in 74% (14/19) of the subjects tested in the evening-light condition. This study shows that non-24-h bright light and sleep-wake schedules can be used to phase shift and entrain human circadian rhythms, despite the presence of the conflicting 24-h zeitgebers. PMID- 2260730 TI - Effects of diet and body fat content on cold-induced anestrus in Syrian hamsters. AB - Mammalian reproduction is inhibited by food shortages, increased foraging requirements, and other factors that decrease the energy available for biological processes. Cold-induced inhibition of reproduction may result from a depletion of available metabolic energy due to the increased requirements for thermogenesis or, alternatively, from mechanisms unrelated to energy expenditure. We examined the relationship between energy availability (in the diet and the body fat stores) and cold-induced anestrus in Syrian hamsters. In experiment 1, hamsters were housed in the cold (5 degrees C) and fed diets that differed in the amount of effort required to ingest them. The number of consecutive estrous cycles was positively correlated with caloric intake and negatively correlated with body weight loss in the cold. In experiment 2, hamsters were fed these diets for several weeks, so that they differed dramatically in body weight and fat content before cold exposure. Half of each group retained the same diet during cold exposure, whereas the other half were fed a regular chow diet. The effects of body weight before cold exposure were less pronounced than the effects of caloric intake during cold exposure. In experiment 3, females were fed different diets before cold exposure, then, during cold exposure, all were fed in a manner that decreased food intake and increased the effort required to obtain food. This energetic challenge exaggerated the effect of prior body weight on the latency to cold-induced anestrus. Thus the latency to cold-induced anestrus in Syrian hamsters is primarily a function of the availability of metabolic energy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260731 TI - Chronic lymph flow and transcapillary fluid flux during angiotensin II hypertension. AB - The roles of the transvascular fluid flux and lymph flow in the distribution of extracellular fluid volume during angiotensin II (ANG II) hypertension were evaluated in 11 conscious dogs. Similarly, the factors regulating the distribution of plasma protein across the microvasculature were assessed. By the second day of ANG II infusion, the thoracic duct lymph flow had increased 58% above control, transcapillary fluid flux had increased 45%, and plasma volume, sulfate space, and interstitial fluid volume remained close to control. In addition, the thoracic duct lymph protein transport had increased 34%, and the accompanying increase in transcapillary protein flux prevented any change in plasma protein mass. Also, at this time, the lymph flow and protein transport from subcutaneous tissue in the hind limb were not increased, and the permeability-surface area product of this region decreased 40%. The origin of the increased thoracic duct lymph flow on day 2 probably was from the splanchnic bed. In conclusion, the increased lymph flow during ANG II hypertension compensated for the increase in transcapillary fluid flux, thus preventing edema formation. PMID- 2260732 TI - Temperature regulation of young coypus (Myocastor coypus) in air and water. AB - Coypus (Myocastor coypus Molina) have recently colonized temperate regions of Europe in large numbers, originating from populations indigenous to subtropical regions of South America. Observations of coypu behavior in the wild and in enclosures under a temperate climate showed a preference for close proximity to water and frequent swimming bouts. Little change was observed in the semiaquatic habit in winter, despite high mortality during this period, particularly among young and adult male coypus. Evidence for constraints on thermal adaptation was sought from measurements in a thermostatic chamber of the resting metabolic rate (RMR) of young coypus caught from wild populations in France and of the body (Tb) and skin (Tsk) temperatures as a function of ambient temperature (Ta). A light heterothermic response with deep Tb falling by 0.8 degree C and stabilizing at a new level of 36.7 degrees C was observed in water and air at Ta below the lower critical temperatures. In common with other semiaquatic mammals, RMR (2.94 W/kg) was high relative to terrestrial mammals of equivalent body mass. Minimal thermal conductance was 0.10 W.kg-1.degree C-1 in air for Ta between -10 and +20 degrees C, and conductance varied in water from 0.24 to 1.18 W.kg-1.degrees C-1 for Ta between 5 and 35 degrees C. The physiological adaptations to cold and particularly the high insulative value of the fur (80-90% of the insulation) help to explain the successful extension of the coypu's range to temperate regions. Energetic costs were nevertheless high in cold water, suggesting that social factors may be implicated in severe winter mortality, particularly dominance hierarchy regulating the persistent use of water bodies even under freezing conditions. PMID- 2260733 TI - Learning to sham feed: behavioral adjustments to loss of physiological postingestional stimuli. AB - The progressive increase in intake of a concentrated (0.8 M sucrose) solution seen when rats are first exposed to the sham-feeding procedure can be prevented by interspersing two real-feeding tests between each sham-feeding test. Under these conditions, sham intake is significantly larger than real intake but significantly smaller than intake on the fifth consecutive sham-feeding test. This result indicates that there is a learned negative-feedback signal based on the association of the taste and postingestive effects of 0.8 M sucrose which extinguishes under consecutive sham-feeding tests. Analysis of the rate of ingestion during the tests revealed that the conditioned negative-feedback signal operates during the first 6 min of a sham-feeding test that follows real-feeding tests. The effect of the absence of an unconditional negative-feedback signal appears from approximately 6 to approximately 20 min during a sham-feeding test. PMID- 2260734 TI - Reduced renal perfusion pressure causes prostaglandin-dependent excitation of R2 chemoreceptors in rats. AB - The activity of multiunit preparations of afferent renal nerve activity (ARNA) and single R2 chemoreceptors was recorded during graded reductions in renal perfusion pressure (RPP) produced by tightening an aortic snare in anesthetized rats. In 13 multiunit preparations an initial RPP reduction from 117 +/- 2 to 101 +/- 2 mmHg caused ARNA to increase 29 +/- 5% above control. Further reductions in RPP produced a 65 +/- 11% increase in ARNA at 80 +/- 1 mmHg, 87 +/- 24% at 59 +/- 1 mmHg, and 127 +/- 38% at 37 +/- 1 mmHg (P less than 0.01 ARNA vs. RPP). Renal blood flow was measured by pulsed Doppler flowmeter in these rats and showed good autoregulation and minimal reduction (-4 +/- 2%) during the initial pressure drop. Ten single R2 chemoreceptors increased their firing rate by 129 +/- 4% when RPP was reduced from 109 +/- 2 to 85 +/- 2 mmHg and showed a peak response of 494 +/- 105% at 27 +/- 2 mmHg. The activity of 11 R2 receptors increased from 3.7 +/- 1.0 to 6.8 +/- 0.8 impulses/10 s when RPP was reduced from 112 +/- 4 to 79 +/- 2 mmHg. Prostaglandin blockade with indomethacin (6 rats) or meclofenamate (7 rats) caused a decrease in basal activity in the same units to 1.8 +/- 0.5 impulses/10 s and eliminated their excitatory response to a similar reduction in RPP (108 +/- 4 to 75 +/- 3 mmHg). These data support a role for R2 chemoreceptors in neurocirculatory reflexes elicited by reductions in RPP. PMID- 2260735 TI - Effect of arginine vasopressin on CSF composition and bulk flow in hyperosmolar state. AB - To find out whether central arginine vasopressin (AVP) plays a role in regulation of cerebrospinal fluid (CSF) composition and of CSF bulk flow (CSFbf) in acute hyperosmolar state, the experiments were performed on 16 anesthetized cats in which the ventriculocisternal system was perfused either with artificial CSF (aCSF; 8 control experiments) or with aCSF containing AVP (10 microU/min, 8 experiments) before, during, and after intravenous infusion of 5% NaCl. In both series, hyperosmotic infusion significantly increased CSF osmolality (CSFosmol) and sodium (CSFNa) and potassium (CSFK) concentration and reduced CSFbf. Administration of AVP significantly influenced the dynamics of changes in CSFNa and slightly affected changes in CSFK concentration induced by infusion of hyperosmotic saline, while it did not modify changes in CSFosmol) and CSFbf. In control experiments, CSFbf was significantly related to plasma and CSF osmolalities and sodium concentrations, whereas in AVP experiments these relationships were markedly suppressed. The results suggest that during acute hyperosmolar state AVP significantly influences sodium handling in CSF and may play a role in adaptation of the brain to hyperosmolality. PMID- 2260736 TI - Basal and pentagastrin-stimulated gastric secretion in young horses. AB - Equine gastric secretion was studied using a gastric cannula model after fasting (basal) and pentagastrin infusion. Gastric secretory rate, pH, osmolality, and electrolyte concentrations and outputs were determined over a 5-h period. Dose response tests estimated that the maximally effective intravenous dose of pentagastrin was between 3 and 6 micrograms.kg-1.h-1. Basal secretory rate was 278 +/- 29 (SE) ml/15 min, and the pH was 2.00 +/- 0.31. Pentagastrin infusion at 6 micrograms.kg-1.h-1 increased secretory rate to 533 +/- 60 ml/15 min and decreased pH to 1.41 +/- 0.11. Basal gastric acid concentration and output were 38 +/- 5 meq/l and 211 +/- 36 mu eg.kg-1.h-1, respectively. Pentagastrin increased acid concentration to 60 +/- 5 meq/l and acid output to 474 +/- 61 mu eq.kg-1.h-1. Gastric fluid osmolality remained hypotonic during both basal and pentagastrin conditions. Sodium concentration remained high in comparison with hydrogen ion concentration, and sodium output increased during pentagastrin infusion. Equine gastric secretion did not attain maximal acid concentrations nor the marked drop in pH, which has been reported for other monogastric species. These data suggest that in the horse a large nonparietal component exists that modifies parietal secretions and is increased by pentagastrin stimulation. PMID- 2260737 TI - Novel determination of filtration coefficient of ovine placenta and intramembranous pathway. AB - We recently reported that distilled water injected into the amniotic compartment is rapidly absorbed by the fetal blood, which perfuses the fetal membranes and the fetal surface of the placenta, i.e., by the "intramembranous pathway." In the present study, we infused warmed distilled water at 2 ml.min-1.kg estimated fetal wt-1 into the amniotic compartment for 6-8 h in 12 chronically catheterized sheep. A steady state was achieved in amniotic fluid, fetal blood, and maternal blood osmolalities in 5.1 +/- 0.3 (SE) h. During the steady state, all of the infused water must pass to the ewe. Because the amount of water directly crossing the fetal membranes into the maternal circulation was not significantly different from zero (3.3 +/- 5.8% of total), we assumed all water crossed the placenta. The placental filtration coefficient was then calculated during the steady state as the infusion rate divided by the changes in the transplacental osmotic gradient and averaged 0.0260 +/- 0.0055 ml.min-1.mmHg-1.kg fetal wt-1. Attempts to correct this value for placental reflection coefficients less than 1 were unsatisfactory; thus the uncorrected value appears to provide the best estimate of the placental filtration coefficient. Similar calculations yielded a value of 0.00137 +/- 0.00025 ml.min-1.mmHg-1.kg-1 for the filtration coefficient of the intramembranous pathway. Thus this method provides a relatively simple new technique for estimating the filtration coefficient of the ovine placenta and intramembranous pathway under steady-state conditions. PMID- 2260738 TI - Effects of portal infusion of hypertonic solution on jejunal electrolyte transport in anesthetized dogs. AB - Jejunal electrolyte absorption was measured in the jejunal loops of anesthetized dogs during infusions of hypertonic solutions via the portal vein. The net Na absorption was not influenced by the 9% NaCl infusion into the inferior vena cava, although it was significantly attenuated by the portal 9% NaCl infusion. This effect may not be due to the osmotic stimulus, since the portal 50% glucose or 6.5% LiCl infusion had no significant influence on the net Na absorption. To determine the mechanism of the decrease in the net Na absorption during the portal hypertonic NaCl infusion, the net Na absorption was measured after the section of anterior and posterior hepatic nerves (SAPH) or intravenous atropine injection. Both SAPH and the intravenous atropine injection completely blocked the effect of the portal 9% NaCl infusion on the net Na absorption. These results indicate that 1) net Na absorption in dog jejunum is depressed by the hypertonic NaCl infusion via the portal vein; 2) the effect is NaCl specific and may not be due to the osmotic stimulus; and 3) the afferent limbs of this effect are the anterior and posterior hepatic nerves, and the efferent limb of this effect is the vagus nerve. Thus the hepatojejunal reflex may play an important role in the regulation of body fluid homeostasis. PMID- 2260739 TI - [Chronic endometritis]. PMID- 2260740 TI - [Chronic placental insufficiency: incidence and causes]. AB - This population study has examined the incidence and determinants of placental insufficiency. Predictors of placental dysfunction were ascertained. They included somatic diseases, gestational complications, a positive obstetric and gynecologic history and a series of constitutional factors. Populations of primiparae+- and multigravidae at risk of placental insufficiency were identified. PMID- 2260741 TI - [Fetal biophysical profile in EPH gestosis]. AB - Fetal biophysical profiles (FBP) have been obtained in 111 women with toxemia of pregnancy at 34-42 weeks. Six biophysical parameters were tested: nonstress test, fetal respirations, motility and tone, amniotic fluid volume and placental maturity. The test findings were compared with pregnancy outcomes, controlling for intrapartum fetal distress. Apgar scores, intrauterine growth retardation, postdate gestation and symptoms of early neonatal adaptation, fetal or neonatal death. The values of FBP were lower with higher severity of gestational toxemia, with the greatest incidence of poor perinatal outcomes in the presence of complicated delivery. PMID- 2260742 TI - [Characteristics of the course of pregnancy and labor in women with Cushing's syndrome and the condition of their progeny]. AB - An analysis of gestational and obstetric histories of 40 women with Cushing's disease has shown that pregnancy is contraindicated during an active phase or partial clinical remission of the disease. Pregnancy is permissible at a prolonged time following the onset of a stable clinical and hormonal remission, bilateral total adrenalectomy and compensation of chronic adrenal insufficiency. No specific therapy is required in the former situation. The adrenalectomized patients need an intensification of replacement therapy and switch to parenteral glucocorticoids ante-, intra- and postpartum. Twenty infants of mothers with Cushing's disease were examined and found to have a normal clinical and endocrine status. PMID- 2260743 TI - [Clinico-morphological characteristics of fetuses and newborn infants of mothers with hemorrhagic shock]. AB - A clinical and morphological analysis has been done using 24 obstetric histories of mothers with hemorrhagic shock (HS) and autopsy protocols of fetuses and newborns who died ante-, intra- or postpartum. Maternal HS was related to placenta previa and presented as a poor general status and microcirculatory disorders, respiratory and adrenal insufficiency. Histologic and electron microscopic studies showed fetal and neonatal lesions in organs and tissues which might be interpreted as irreversible shock. Reduction of neonatal mortality dictates further efforts in the prevention of hemorrhagic complications in parturients. PMID- 2260744 TI - [Studies of the fetal condition in present-day perinatology]. PMID- 2260745 TI - [Reflex labor induction in premature labor complicated by premature rupture of fetal membranes]. AB - Labor induction in impending premature delivery complicated by premature rupture of the membranes is controversial. Problems arise both with choice of a mode of delivery and induction manoeuvres to be used in biologically premature delivery. The paper addresses the results with a reflex method of labor induction based on transcutaneous electroneurostimulation (TENS). An appropriate TENS regimen was found to be a highly efficient method of labor induction allowing one to reduce the incidence of perinatal complications. PMID- 2260746 TI - [Stress normal values of the indicators of colloid osmotic pressure in parturients after cesarean section]. AB - The paper describes changes in mineral and protein metabolism and renal function in mothers with an uncomplicated ++post-cesarean course. Stress norms of mothers delivered by cesarean section were quantitatively different from those of surgical patients: the former had lower values of osmolality and glucose levels and a marked reduction in total protein and albumin levels. This warrants fluid therapy controlling for the changes induced by the operation. PMID- 2260747 TI - [Retrospective analysis of the causes of cervical injury during labor]. AB - Risk factors for intrapartum injury of the uterine cervix have been evaluated using computer and mathematic techniques. The factors were analyzed and compiled into a diagnostic table determining antepartum prediction of cervical injury. PMID- 2260748 TI - [Epidemiology of induced abortion and contraception]. AB - This article describes prevalence and distribution patterns of induced abortion and contraception in various regions of the USSR. Selective studies have elucidated a spectrum of factors of abortion and contraception prevalence, their roles in birth control and priorities in implementation of updated methods of induced abortion prevention. PMID- 2260749 TI - [Reproductive and menstrual functions in women after cryosurgical treatment of cervical diseases]. AB - Short- and long-term results of patients with a history of cryosurgery of cervical pseudoerosions suggested a lack of its adverse effects on reproductive and menstrual function. Cryotherapy of the uterine cervix resulted in normalization of local immunity, an advantage in the presence of a cervical factor of infertility. PMID- 2260750 TI - [Immunoglobulin levels in endometrial secretion in patients with chronic endometritis]. AB - Immunoglobulin levels have been assayed in endometrial secretions from 30 patients with chronic, 25 patients with acute endometritis and 15 normal women. Concentrations of IgG, IgA and, especially, IgM were high in patients with chronic endometritis as compared with the normal women and patients with acute endometritis. These findings suggest that immunoglobulin studies may be used as a diagnostic and predictive test. PMID- 2260751 TI - [Alternative solutions in the treatment of patients with combined benign endometrial and myometrial pathology]. AB - The study included 96 women with combined benign hyperplastic uterine conditions. Half of them underwent a radical uterine resection and were examined at 3.1 +/- 0.2 years following the operation. The rest were randomly selected as matched pairs and were evaluated at 4.3 +/- 0.13 years following multicomponent treatment including hormones (n-26) and cryohormonal treatment (n-22). Analysis of results revealed a complex pathogenesis of this disease of the reproductive tract, presenting as severe postoperative vegetoneurotic disorders. Potential of an adequate conservative treatment in preserving specific female functions was determined. PMID- 2260752 TI - [Immunological studies of peripheral blood in patients with external genital endometriosis and infertility]. AB - Immunoregulatory lymphocytes of SD2-, SD4-, SD8- and SD2-phenotypes have been assayed using monoclonal antibodies in peripheral blood of infertile women with external genital endometriosis and tubal-peritoneal infertility. The tested cells did not markedly differ from those in control fertile patients. Serum concentrations of immunoglobulin M were increased in women with endometriosis. Immunoglobulin concentrations widely varied in the peritoneal fluid, with a statistically significant elevation of IgA and IgM in women with tubal-peritoneal infertility. PMID- 2260753 TI - [Morphological substantiation of selection of the method of surgical treatment of patients with prolapse of internal genital organs]. AB - Morphology of uterine ligaments and the vaginal mucosa has been examined in 61 patients with uterine prolapse in order to provide guidelines for an optimum management with respect to tissue functional status. Specimens were obtained intraoperatively and examined in a usual microscope and a S-570 Hitachi scanning electron microscope (Japan). The study suggests that morphologic evaluation of the vaginal walls and uterine ligaments provides an exact measure of tissue status, offering an optimum choice of treatment in these patients. PMID- 2260754 TI - [Current aspects of surgical treatment of prolapse of internal female genital organs]. AB - A study in 128 women with variable degrees of prolapse of the internal genitalia has identified significant functional abnormalities of both the genital and pelvic organs. Combined biphasic surgical treatment was performed simultaneously or at an interval of 3-6 months. The operation consisted in fixation of the uterus (its stump or the vaginal dome) using an aponeurotic flap and colpoperineolevatoroplasty. Long-term results were evaluated at 0.5 to 7 years. Complete anatomic and functional rehabilitation was achieved in 95.4% and a significant improvement in 3.8% of the patients. PMID- 2260755 TI - [Use of ultraviolet irradiation of blood in obstetrical and gynecological practice]. PMID- 2260756 TI - [Work experience of a lawyer in a women's consultation clinic]. PMID- 2260757 TI - [Therapeutic tactics in suppurative-inflammatory adnexitis]. PMID- 2260758 TI - [The role of A. Ia. Krassovskii in founding of the first Russian school for obstetricians and gynecologists]. PMID- 2260759 TI - [International congress on "Lasers and medicine"]. PMID- 2260760 TI - The fine venous architecture of the major duodenal papilla in human beings. AB - After injecting Indian ink or sulphate of barium backwards into the venous trunks that drain the 2nd portion of the duodenum, the author describes 3 venous networks, continuous to the major papilla and which differ in their topography and morphology of their nets. From the functional point of view, he believes that the traction or compression of the collectors' walls might cause turgidity in the deep network, regulating the bile-pancreatic outlet as well as not allowing the duodenal reflow. The author states that during papillotomies the bleeding is insignificant, because the thick veins lie in the body and at the base of the papilla. PMID- 2260761 TI - Localization of concanavalin A--binding sites on neuroepithelial cells in early newt's neurula after treatment with noradrenalin. AB - The concanavalin A (Con A)--binding sites on the cell surface of newt's neural plate and groove in norm and following treatment with noradrenaline (NA) were examined ultrastructurally. The changes in the distribution of Con A--binding sites as well as structural changes of endocytic vacuoles in experimental conditions were described. The present results suggest that the differences in the Con A--binding were caused by receptor interaction of the plasma membrane glycoconjugates and the applied neurotransmitter. PMID- 2260762 TI - Morphological characteristics of the A10 catecholaminergic group of neurons in the human midbrain. AB - The authors examined ten serially sectioned human midbrains stained with luxol fast blue and/or cresyl violet. They found the neuromelanin-containing neurons in the central (CL) and rostral (RL) linear nuclei, the interfascicular (IF), the paranigral (PN), and the parabrachial pigmented (PB) nuclei, as well as in the medial longitudinal fasciculus and the dorsal nucleus of the raphe. The CL nucleus measured 4.7 mm x 1.9 mm, the RL 2.9 mm x 0.6 mm, the IF 2.8 mm x 0.6 mm, the PN 1.3 mm x 0.8 mm, and the PB 4.4 mm x 0.7 mm. The number of pigmented neurons per section was 9.4 in the CL, 13.5 in the RL, 51.7 in the IF, 41.8 in the PN, and 33.1 in the PB nucleus. The pigmented neurons, which were fusiform, oval or multipolar, ranged from 9.3 microns x 9.0 microns to 62.0 microns x 25.0 microns in size. Clustering of the cells was most prominent in the IF and PN nuclei, as well as in the lateral parts of the PB and RL nuclei. The authors concluded that: 1. the CL and PB were the largest nuclei; 2. the greatest cellular density was in the IF and PN nuclei; 3. the largest pigmented neurons were present in the RL and PB nuclei, and 4. the CL and RL nuclei were more complex than the other nuclei of the A10 catecholaminergic group. PMID- 2260763 TI - Electromyographic study of the trapezius (pars superior) and serratus anterior (pars inferior) in free movements of the arm. AB - The emg activity of the trapezius (pars superior) and serratus anterior (pars inferior) mm. in free movements of the arm was examined in 25 young adult volunteers of both sexes, using a 2-channel TECA TE4 electromyograph with single coaxial needle electrodes. The records obtained showed that: 1) In abduction, flexion, adduction and extension of the arm, TS and SI act synergically; 2) The activity of both muscles increases gradually in abduction and flexion when the scapular rotation occurs. TS also acts as scapular elevator, a movement which occurs simultaneously with abduction and flexion; 3) The activity of both muscles decreases gradually in adduction and extension which controls the return of the scapula and clavicle to the initial position; 4) In hyperextension TS and SI are inactive. PMID- 2260764 TI - [The fine structure of the nucleus of the facial nerve of sheep and goats]. AB - The nucleus of the facial nerve in sheep and goats measures 4 to 6 mm and is divided into 4 groups (dorsal, medial, lateral, intermediate). Electronmicroscopically 5 neuronal types and 4 classes of synapses could be detected. Differences between the species are reduced to the arrangement of the rough endoplasmic reticulum and number of axo-somatic synapses. PMID- 2260765 TI - ["The Venus of Pest"--expedition of an anatomical beauty]. AB - The Semmelweis-Museum in Budapest, Hungary, has a small collection of anatomical wax models. Studying the correspondence of the Austrian emperor Joseph II., then King of Hungary with representatives of the Hungarian administration, we were able to find out the origin of these models, their transportation to Hungary and their large significance in anatomical teaching at the end of the 18th century in Hungary. These models are the result of a long-lasting cooperation between artists and anatomists, particularly in Italy. Their artistic climax is reached during the second term of the 18th century, reflecting the complex interaction of contemporary sociocultural trends i.e. popularization of results of scientific research, traits of enlightenment combined with an artistic hyperidealistic typization as known from classical antiquity and sponsored financially as a means of imperial representation. The aim of the study was to point to the eminent importance of this collection as a monument of cultural heritage. PMID- 2260766 TI - The penis morphology of the four-eyed opossum Philander opossum. AB - The penis of the Philander opossum is found in post-scrotal position and attached to the schiatic arch by means of a suspensory ligament. The bulk of the penile musculature is formed by the ischio-cavernosus (IC) and bulbo-spongiosus (BS) muscles, which converge caudo-medially to join the radix penis. The paired levator penis muscles are encaised in the radix and fuse to each other ventrally to the urethra forming a long tendon. The erectile tissue arisen from the BS forms the corpus spongiosum of the urethra and the corpus cavernosum starts within the IC. The urethral mucosa is longitudinally folded and lined with transitional epithelium. The body of the penis shows a pronounced sigmoid flexure which runs ventro-dorsally, with ventral, intermediate and dorsal segments. The retractor penis (RP) muscles insert in both sides of the penile dorsal curvature. The fascia of the penis is thick and surrounds the corpus cavernosum, the corpus spongiosum of the urethra and the final part of the levator penis muscles. The body-glans transition initiates with the formation of a mid- ventral groove which progressively reaches the urethral lumen; the mid-dorsal groove initiates farther distally and also reaches the urethra. The transition of urethra into urethral grooves is characterized by the modification of transitional into stratified squamous epithelium. The glans penis is bifid and has slender tips. Each urethral groove are situated on the medial-ventral surface of each glands tip. The penis in the non-erect state is partially situated in the preputial cavity; when erected, projects through the cloaca, unfolding the sigmoid flexure. The preputial sac is formed by the lamina externa (without hair follicles but having preputial glands), the lamina interna (which shows cornified areas and delimit externally the opening of the preputial cavity) and the visceral lamina, very folded and with numerous cornified spicules. PMID- 2260767 TI - [The blood vessel supply of the testis in Pekin drakes (Anas platyrhynchos L.). Macroscopic, light microscopic and scanning electron microscopic studies]. AB - Testes of Pekin ducks were macerated following injection with plastic at the period of maximal spermatogenesis which occurs during spring. The right and left A. testicularis arise from the A. renalis cranialis. The right testis is additionally supplied by an irregularly occurring A. testicularis accessoria. After penetrating the testicular capsule the arteries run to the centre of the testis and terminate as branching Aa. radiatae centrifugales. The seminiferous tubules are surrounded by intertubular and peritubular capillaries forming a rope ladder-like system. Venules and veins run peripherally to enter the vein converge into the testicular hilus, and unite to form 2 Vv. testiculares which empty into the V. cava caudalis. Regulation of testicular blood supply is achieved by throttle devices depending on the avian seasonal cycle. The coiled and step-like course of the vessels results in a sufficient contact between blood and seminiferous tubules. Testicular veins surrounding the arteries might be an equivalent of the steroid transfer mechanism in the mammalian spermatic cord. PMID- 2260768 TI - Teratogenic effects of coherent light on chick embryos. AB - In this work we study the possible teratogenic effects of laser light with very low surface power densities. In all the cases we confirmed embryonic anomalies that were more manifest and generalized as earlier the stage where the embryos were exposed to irradiation. PMID- 2260769 TI - Immunocytes in the human fetal pancreas--a contribution to developmental immunoendocrinology concerning diabetes mellitus and organ cultivation. AB - The studies were performed on 103 samples of human fetal pancreas tissue (10th to 26th week of gestation). Of the mothers, 14 had insulin dependent type I diabetes mellitus (IDDM), and 33 of the samples were examined before and after cultivation for 14 days. 3 samples taken from fetuses in the 14th week of development (mothers without metabolic disorders) were examined in the electron microscope. Lymphocytes are generally irregularly distributed within the tissue. Groups of 3 to 5 lymphocytes are found in addition in the 12th week of development, and larger clusters (10 to 15 lymphocytes) appear from the 14th week onward. Relating these quantitative results to the 3 phases of early fetal islet organ development, it can be seen that lymphocyte numbers increase from the 10th to the 26th week of development. The significance of this is discussed in connection with the development of the immune system. In view of the contemplated transplantation of fetal pancreas tissue as treatment for IDDM, it means that a relatively low immunogenicity can be expected up to the 14th week of development. Thymic differentiation is not complete before the 17th week, and differentiation of the lymph nodes and spleen continues until weeks 20 to 23. Although IgG antibodies are transferred across the placental barrier already in about the 8th week, this flux does not reach its maximum until the 32nd week. Endogenous antibody synthesis in the fetus does not start until the 18th week. IDDM of the mother during fetal development (10th to 26th week) does not increase the lymphocyte number in the pancreas. This also applies to tissue that has been cultivated for 14 days after reaching the same stage of development. PMID- 2260770 TI - The comparative morphology of the muscle tissues and changes in constituents in the pig types. AB - The authors have revealed the main value characteristics of pork production by testing in five different types of pig the volume of contractile and collagen proteins, that of proteoglycans, the constituents of blood and the enzymes of the blood plasma. The contractile proteins of the muscle tissues basically determine the quality of pork. The same applies to the water retention capacity, colloidal characteristics and glycogen content of meat. The amount of contractile proteins has decreased in the best meat producing types of pig. Parallel with the decrease of white meat, and with the increase in the volume of ham, chop and chuck the contractile protein content of muscles decreased. The scientific fact according to which there is a certain correlation among the changes in the volume of contractile proteins, blood sugar level, blood serum CPK and the intensity of activity of the LDH enzymes promotes the qualifying of live animals and the work of the geneticists aiming at the increasing of the contractile protein content of the muscle tissues of pigs by selection. According to tests carried out by us the primary cause of PSE changes is a decreased volume of contractile proteins. Increased stress sensitivity and all the other factors have but a secondary importance and are all consequential. The decrease in the quantity of contractile proteins or--it is better to put it this way--the lack of the proper amount of such proteins characterizing a fully developed pig's organism is caused by the nowadays usual breeding technologies and can be well explained by those selection activities which aim at a one-sided kind of pork production. PMID- 2260771 TI - [The development of the bovine stomach: morphological and morphometrical analysis. I. Morphogenic observations of the ruminoreticulum]. AB - Forty-two embryos and fetuses of Frisian cattle, distributed onto 14 groups on the basis of crown-rump lengths between 1.3 cm (about 23 days) and 9.5 cm (70 days), were to study the morphogenesis of the bovine stomach. The work is divided into three parts. Part 1 deals with the ruminoreticulum and parts II and III the omasum and abomasum. PMID- 2260772 TI - Development of the retina in the porcine fetus. A light microscopic study. AB - Morphogenesis of the porcine retina was studied using light microscopy from 4 weeks of gestation until birth (18 to 310 mm crown-rump length), and compared with the adult stage (6 months). Tissue samples were examined from the posterior and peripheral parts of the retina. At 18 mm the retina consists of an inner marginal layer and an outer layer of neuroblastic cells. At 18-40 mm the latter layer is divided into an inner and an outer neuroblastic layer by the transient layer of Chievitz. Subsequently, the development of the different retinal layers begins at the inner retinal border and moves progressively outwards; it also spreads from the posterior to the peripheral part of the neural retina. Many cells of the inner neuroblastic layer are prospective ganglionic cells which migrate inwards, thus forming the ganglion cell layer and the inner plexiform layer at 90 mm. At 120 mm, primitive horizontal cells appear within the outer neuroblastic layer. Separation of this layer into the inner nuclear, outer plexiform and outer nuclear layers is first evident at 180 mm. At this stage all retinal layers are present, except the layer of the photoreceptor cells which is not widespread until at 220 mm. The inner and outer segments of the photoreceptor cells lengthen considerably during the last month of gestation. During the late fetal stage the nerve fiber layer, the inner and outer plexiform layers and the layer of rods and cones all continue to increase in thickness. Concurrently, the ganglion cell layer and the inner and outer nuclear layers have reached their maximal thickness and become thinner. After the total thickness of the neural retina amounts to approximately 180 microns at two to three weeks before birth, it then thins to approximately 160 microns in the adult stage. PMID- 2260773 TI - Structural and ultrastructural differentiation of cell types in the gills of the tench (Tinca tinca, L.). AB - This study used 22 tench of 25-30 cm in length and weighing roughly 200 g. After sacrifice, the gill arch was extracted and fixed in 5% glutaraldehyde for structural, ultrastructural and morphometrical study. Tench gills consist of primary lamellae which are perpendicular to numerous secondary lamellae in which the respiratory barrier is located. A study was made of the structures which make up that barrier and of the multi-layered epithelium situated in the interlamellar space, which is closely linked to maintaining of internal balance in the fish. PMID- 2260774 TI - Histo- and cytochemical studies on the distribution of acetylcholinesterase positive nerve fibers in the goat adrenal gland. AB - The distribution patterns of acetylcholine esterase positive nerve fibers in the goat adrenal gland is described. Some positive cells are observed within the capsule. Terminals were identified in both the medulla and the cortex of the gland. PMID- 2260775 TI - Binocular dissecting microscopic studies on the density of toruli tactile in the La Mancha goat. AB - The Merkel cells and associated nervous terminal plates have been called toruli tactiles (TT). These structures can be ubiquitously seen on the shaved hairy skin after staining with a methylene blue solution. Four La Mancha goats of both sexes were examined for the density of TT. TT were visually located under a binocular dissecting microscopic (14x) and then the number of TT in the field was directly counted. The density of TT in different corporal areas of the body surface was estimated from the mean of several two-cm square samples of skin. The results obtained are as follows: The mean number per two-cm square on the whole body surface ranged from 10.06-11.36 in the male specimen and from 12.98-14.32 in the female specimen. The density of TT was rather high in the temporal and buccal areas, on the neck, chin and cranial breast, and on the lateral surface of the arm, thigh and leg. Density was moderate in the fronto-parieto-occipital area (female), on the loin and buttocks, in the upper costal, lower caudo-costal, xiphoid-umbilical and umbilical-pubic areas, and on the lateral surface of the forearm. TT were absent or very few in number on the nose and chin, the scrotum, caudal-pubic area of males, the udder, the vulva, and the digitorum manus et pedis. PMID- 2260776 TI - The process of secretion in swine apocrine sweat glands. AB - The secretory process in swine apocrine sweat glands were studied by electron microscope. The sweat appeared to result from three different mechanisms: (a) fluid transport, probably involving a region of complex cellular interdigitations adjacent to the basement membrane, (b) exocytosis of vesicles, which in this species seem to be derived from the Golgi apparatus and finally (c) apocrine secretion. PMID- 2260777 TI - Postnatal development of the lower canine and cheek teeth of the pig. AB - Postnatal development of the teeth of German Landrace and Gottingen Miniature pigs was studied by measuring the areas of each tooth visible on lateral radiographs of the mandibles. It was concluded that the appearance of the teeth at each stage, and the relation of their growth to that of the rest of the masticatory apparatus, relates mainly to postnatal changes in the relative location of the jaw pivot. PMID- 2260778 TI - Autonomic innervation of the equine urinary bladder. AB - The distribution and density of intrinsic autonomic nerve fibers and cells were studied in the equine urinary bladder by means of the peroxidase-antiperoxidase immunohistochemical method to localize tyrosine-hydroxylase (TH), and by means of a histochemical technique to detect acetylcholinesterase (AChE) activity. The results suggest that the equine urinary bladder, like that of other mammalian species, possesses a rich autonomic innervation which includes catecholaminergic and acetylcholinesterase positive nerves. At least a part of these nerve fibers have an intrinsic origin from ganglion cell bodies within the bladder wall. PMID- 2260779 TI - Effects of purified Pasteurella multocida dermonecrotoxin on cartilage and bone of the nasal ventral conchae of the piglet. AB - The effect of intramuscular injection of purified dermonecrotoxin (DNT) from Pasteurella multocida type D on the nasal ventral conchae of piglets was studied. Severe atrophy of the conchae was observed 4, 6, and 10 days after injection (p.i.d). Lesions were observed in conchae cartilage and bone. Cartilage changes observed were the absence of chondrocyte maturation and hypertrophy, hyaline cartilage invasion by fibroblast-like and multinucleated cells, and endothelium damage with haemorrhages along the cartilage. Intramembranous bone was absent on p.i.d. 4, 6, and 10. Lamellar bone trabeculae were rarefied on p.i.d. 4 and almost absent on p.i.d. 10. Trabeculae were either normal or had the aspect of a dissolved bone matrix, leaving only irregularly oriented collagen fiber bundles. The number of osteoclasts was increased, especially the subperiosteal osteoclasts at the eccentric side of the scrolls. The osteoblasts appeared normal or their cytoplasm was dilated by vacuoles. It is concluded that the macroscopic conchae atrophy results from histological alterations and subsequent loss of both cartilage and bone. Further investigation is necessary to know whether the toxic effect of DNT on cells and matrix is direct or dependent of the vascular damage. PMID- 2260780 TI - Myosin isozyme expression in response to stretch-induced hypertrophy in the Japanese quail. AB - When skeletal muscle is subjected to stretch it undergoes a rapid increase in muscle mass. However, the effect of stretch on the native myosin isozyme content of muscle has received attention only recently. Using the Japanese quail to investigate stretch-induced hypertrophy, we demonstrated an increase in the expression of fast myosin in the predominantly slow anterior latissimus dorsi muscle (ALD). The fast myosin content of the control quail ALD is not sufficient to be quantified on native myosin pyrophosphate gels. After 33 days of stretch, the fast myosin content (N = 10) averaged 16 +/- 11% in the stretched muscles and reached a maximum of 40%. Mean hypertrophy in the stretched muscle, as indicated by muscle weight, was 247 +/- 91% (range, 168-378%). Fast myosin was consistently expressed in muscles with hypertrophy greater than 250%. Muscle fiber size from the stretched muscles contained a greater number of fibers with small cross sectional areas than was observed in controls. These results indicate that substantial remodeling occurs in the stretched ALD muscle of the Japanese quail. PMID- 2260781 TI - Whole population cell kinetics of jejunal and colonic epithelium in lactating dams. AB - Previous studies make it likely that the response of the intestinal epithelium as a whole to lactation is different from that observed in the crypt population alone. We confirm this difference by whole population cell kinetics measurements of jejunal and colonic epithelium in mice that have been suckling pups for various lengths of time. We found that the fraction of cells in S phase in jejunal epithelium was significantly increased after only 1 week of lactation, maintained this elevated level after 2 weeks of lactation, but returned to normal during the third week of lactation. The cell number density in jejunum was also significantly higher after 2 and 3 weeks of lactation before returning to normal by 4 weeks. In the colonic epithelium no changes were found in the distribution of cells in G1, S, and G2 + M phases. However, a significant increase in cell number density was observed after 2 weeks of lactation, followed by a sharp decrease to a level significantly below that of normal mice after 3 and 4 weeks of lactation. We conclude that the observed significant increase in the fraction of S phase in jejunal epithelium of lactating mice is probably due to a smaller relative expansion of the villus population when compared with the expansion of the crypt population. Our data also indicate that a number of cell kinetic parameters in the intestinal epithelium of lactating mice are changing throughout the period of lactation. Thus the intestinal epithelium is probably not in a steady state during lactation. PMID- 2260782 TI - Estimating anatomical-functional position coordinates in liver tissue. AB - Hepatocyte enzyme activity was demonstrated by examining adult C57BL/6 mouse liver cryostat sections under a succinate dehydrogenase (SDH) histochemical reaction, and quantified by microspectrophotometry and microdensitometry. The hepatocyte SDH activity gradient along the path between the portal veins (PV) and efferent terminal hepatic venules (THV) was analyzed by measuring the concentration of the chromophore precipitated in 10 consecutive hepatic parenchymal domains located along imaginary lines drawn across the entire PV-to THV distance. The profiles of intensity or of normalized relative optical density obtained on a high number of lines were correlated with distance values along the PV-to-THV pathway, enabling us to establish a general mathematical function relating SDH activity (chromophore concentration) to position values on a scale of 0 to 10 corresponding to the theoretical PV-to-THV distance. The equation can be used to interpolate the SDH activity surrounding any intrahepatic object located between the PV and the THV, thus making it possible to calculate the object's anatomical-functional position coordinates in the liver acinus. To demonstrate how this method is used, we have calibrated the intrahepatic position of hemopoietic foci induced in the liver tissue of adult mice treated with phenylhydrazine (PHZ), and show that these foci are located on coordinate 3.31 (maximum range 1.25-4.86) of the sinusoidal domain-that is, on the borderline between Rappaport's acinar zones 1 and 2. PMID- 2260783 TI - High-resolution scanning electron microscopic studies on the three-dimensional structure of the transverse-axial tubular system, sarcoplasmic reticulum and intercalated disc of the rat myocardium. AB - The three-dimensional structure of the transverse-axial tubular system, sarcoplasmic reticulum (SR), and intercalated disc of the rat left ventricle was examined by high-resolution scanning electron microscopy after removal of the cytoplasmic matrices by the osmium-DMSO-osmium procedure. In the intermyofibrillar space, the transverse tubules (T-tubules) are accompanied by longitudinally oriented axial tubules and together form a transverse-axial system. The junctional SR is usually small but occasionally medium or large in size and couples with the T- or with the axial tubules. On the surface of the junctional SR facing the T- or the axial tubule, tiny junctional processes are seen. One or two sarcotubules, the so-called Z-tubules, frequently run parallel to the T-tubule. The sarcotubules derived from the junctional SR or from the Z tubule run longitudinally or obliquely and form polygonal meshes around the myofibrils. On the surface of the SR at the H-band level, small fenestrations of 12-40 nm in diameter, and tiny hollows 8-20 nm in diameter are seen. Bulbous swellings of the SR, the corbular SR, are preferentially seen near the Z-band. The large and flat SR, known as the cisternal SR, intercalates among the SR meshes. In the subsarcolemmal space, the sarcotubules form a multilayered network (peripheral SR). The cisternal SR is frequently intercalated in these meshes and closely associated with the inner surface of the sarcolemma. The intercalated disc appears as a prominently undulated membrane demarcating the border between two adjacent heart muscle cells, and occasionally small projections 60-90 nm in diameter and 200-600 nm in length display on its surface. PMID- 2260784 TI - Effects of temperature and buffer composition on calcium sequestration by sarcoplasmic reticulum and plasma membrane of rabbit renal artery. AB - 45Ca electron microscopic autoradiography was used to examine the effects of buffer composition and temperature on the distribution of calcium in rabbit renal artery smooth muscle cells. The results show that the relative distribution of calcium is dependent on both the buffer used (Tris or Krebs) and the temperature of the bathing solution (25 degrees C or 34 degrees C). Krebs buffer at 34 degrees C gave the highest relative activity in the plasma membrane, sarcoplasmic reticulum, and mitochondria. Buffer and temperature had little effect on the relative activity of the nucleus or cytoplasm. Next, we identified the cellular sites of calcium accumulation after 5, 15, 30, or 60 min exposure to 45Ca in Krebs buffer at 34 degrees C. The results show that sarcoplasmic reticulum and plasma membrane are the primary sites of calcium accumulation during influx into these cells. Although the amount of 45Ca in the cell continues to increase with longer exposure, the relative distribution of calcium is essentially the same after 5 or 60 min. The data also indicate that the relative activity of plasma membrane + sarcoplasmic reticulum (a combination site that includes sarcoplasmic reticulum within a mean distance of 275 nm of the plasma membrane) is similar to the membrane alone and is lower than the sarcoplasmic reticulum alone. PMID- 2260785 TI - Distribution pattern of acetylcholinesterase in early embryonic chicken hearts. AB - To study the developmental appearance of acetylcholinesterase in early embryonic hearts, an enzyme-histochemical study was carried out in chicken embryos ranging from cardiogenic plate to late tubular stages. Initially acetylcholinesterase is present in all cells of the (future) myocardium. When 13-14 pairs of somites have developed, i.e., shortly before blood propulsion starts, acetylcholinesterase selectively disappears from the ventral and lateral wall of the developing ventricle. Slightly later, when 18-19 pairs of somites have developed, acetylcholinesterase also disappears from the dorsal and anterior wall of the atrium. High concentrations of acetylcholinesterase remain present in the outflow tract and lower concentrations in a continuous tract along the lesser curvature of the heart, the atrial side of the atrioventricular canal, and the left wall of the atrium. In late tubular stages of heart development, acetylcholinesterase is reexpressed in the inner myocardial layer of the ventricle, i.e., in the developing trabeculae and the ventricular side of the atrioventricular canal, where it is continuous with the acetylcholinesterase-expressing cells of the atrial side of the atrioventricular canal. The expression pattern of acetylcholinesterase in early embryonic chick hearts coincides with that of areas that control the conduction of the impulse and may reveal a cholinergic signal transduction system that is responsible for a coordinated contraction pattern of the myocardium prior to the development of the definitive conductive system. PMID- 2260786 TI - Shaping, invagination, and closure of the chick embryo otic vesicle: scanning electron microscopic and quantitative study. AB - Scanning electron microscopy, light microscopy, and morphometric analysis were used to study the morphological changes of the otic placode and vesicle before and during invagination and closure processes. Our results reveal that the otic placode undergoes shaping between stages HH9 and HH12; during this period the rostrocaudal axis is shortened, while the lateromedial axis of the placode lengthens. The presence of long cytokinesis bridges during this period suggests that cellular displacements after mitosis may participate in the shaping of the otic placode. The shaping process appears to facilitate the approach of the otic placode to the neural tube. From stage HH12 on, the otic anlage gradually becomes a U-shaped structure with its medial portion in intimate apposition to the rhombencephalic neural tube. The coincidence in time between the beginning of intimate otic anlage-rhombencephalon contact and active invagination suggests that these two processes are related. Changes occurring at the edges of the otic vesicle until their disappearance in stage HH17 suggest that, in addition to a process of invagination, the edges of the otic anlage become bent. During closure, cells at the edges of the otic vesicle differ in apical morphology according to their topographical location: The cells between the rostral and lateral edges have elongated apices, in contrast with the polygonal shape of the cell apices in other places of the edges. In the opposite side (between the caudal and medial edges) cell death is observed. Closure of the otic vesicle conceptualized as a zipper-like model is discussed. We propose that early development of the otic anlage takes place in four stages: 1) shaping (stages HH9 11); 2) triggering of the invagination (stage HH12); 3) early invagination and lateral bending (stages HH13-15); and 4) late invagination and closure (stages HH16-17). PMID- 2260787 TI - Morphometry and frequency of afferent synaptic terminals in the rabbit dorsal lateral geniculate nucleus. AB - Morphological and morphometric features of the retinal synaptic terminals (RLP) and cortical synaptic terminals (RSD) were analyzed in the alpha E sector of the rabbit dorsal-lateral geniculate nucleus (dLGN). A methodological approach was selected which allowed us to determine volume of the neuropil and elsewhere record variations in the size and distribution of the two types of terminals found in the three zones (superior, middle, and inferior) from up to down into which the alpha E sector of the dLGN was divided. After obtaining an isotropic, uniform, and pseudorandom (IUR) sample, the terminals were examined on the basis of a set of morphometric parameters. An analysis of these data showed the retinal terminals (RLP) to be more numerous and to occupy a greater total area of the neuropil in the dorsal (superior) zone of the nucleus, whereas the number and total area occupied by cortical terminals (RSD) did not vary in the superior, middle, and inferior zones. Upon comparing the two types of terminals, the RLP were larger and more widely distributed, the greatest differences between the two appearing in the dorsal (superior) zone of the dLGN. PMID- 2260788 TI - Cholinesterase activity in terminal Schwann cells associated with Ruffini endings in the periodontal ligament of rat incisors. AB - A nonspecific cholinesterase activity was demonstrated in terminal Schwann cells associated with Ruffini endings in the periodontal ligament of rat incisors at the light and electron microscopic levels. The terminal Schwann cells are ultrastructurally characterized by a well-developed Golgi apparatus and rough endoplasmic reticulum. The cells in this study were positive for nonspecific cholinesterase, whereas ordinary Schwann cells associated with more proximal nerve fibers reacted negatively. The reaction products were densely deposited in the cisternae of the rough endoplasmic reticulum and along the nuclear envelop. A moderately intense labeling was found in the cytoplasmic extensions, in which the reaction products gathered in caveolae and vesicles. These findings indicate that nonspecific cholinesterase is a useful marker to distinguish terminal Schwann cells from ordinary Schwann cells and that the enzyme may be synthesized in the rough endoplasmic reticulum and conveyed toward the axon terminals. Since this enzyme has been known to be shared by the inner bulb of Pacinian corpuscles and the lamellar cells of Meissner's corpuscles, its possible involvement in mechanoreceptive functions in these specialized Schwann cells deserves further investigation. PMID- 2260789 TI - Radioactivity in human milk. AB - A brief introduction outlines the sources of radionuclides in the environment, their diffusion and transfer to different environmental compartments and their pathways to individuals; definitions of the main quantities and measurement units used in the study are included. A review is given on published data concerning the radioactive contamination of human milk after the Chernobyl accident. The authors' investigation on breast milk contamination in Italy in the same period is discussed together with an examination of the natural radioactive content. Finally, possible future developments and prospects of the research on this issue are explored. PMID- 2260790 TI - Reference values for essential and toxic elements in human milk. AB - Dependable reference values (RVs) for the concentration ranges of health-related elements in human biological fluids and organs are to date of acknowledged importance for an early recognition of pathological states. On the other hand, the present lack of reliable data on levels to be considered as baseline values for elements of major concern from a toxicological, environmental and nutritional point of view demands the development of experimental procedures capable of satisfying the requirements of detection power, specificity and applicability on a large scale necessary to generate vast amounts of reliable measurements. As part of an overall monitoring program, an investigation was undertaken with the following two aims: a) the present suitability of inductively-coupled plasma atomic emission spectrometry (ICP-AES) to identify and quantitate minor and trace elements in human milk with the necessary accuracy and precision; b) assessment of RV concentrations for Al, Ba, Cd, Cr, Cu, Fe, Li, Mg, Mn, Ni, Pb and Zn. Four population groups were selected (each with 9 subjects) resulting from the various combinations of smokers and non-smokers from an urban or a rural environment. Strict eligibility criteria were adopted in order to select only women in good health, no known occupational exposure and whose nutritional habits could be described in detail. A scrupolous and systematic approach was adopted to minimize every possible source of elemental contamination from the sampling step onwards. Digestion of samples was attempted both with mixtures of strong acids and by resorting to acid-assisted mineralization in a microwave oven. Both methods were satisfactory for subsequent introduction into the torch of the ICP-AES system. The outcome of this pilot study gave the following median RVs for concentration (in mg/kg): Al, 0.14; Ba, 0.013; Cd, 0.002; Cr, 0.016; Cu, 0.40; Fe, 0.72; Li, 0.004; Mg, 29.4; Mn, 0.006; Ni, 0.05; Pb, 0.016; and Zn, 3.08. PMID- 2260791 TI - Protein and lipid composition of human milk and infant formulas: comparison and nutritional consequences. AB - This work results from some research carried out by the authors during the last few years in nutrition field. The data collected allowed to compare protein and lipid composition of infant formulas with human milk and to evaluate the influence of such feedings on plasma aminoacid levels and erythrocyte fatty acids. In spite of different infant formula compositions with respect to human milk, our nutritional studies did not demonstrate physiological differences between breast and bottle-fed infants if formulas provide with an adequate intake of protein and linoleic acid. PMID- 2260792 TI - Kinetics of excretion in milk of some antimastitis drugs. AB - A study on the kinetics of excretion in milk of some antimastitis drugs is described. The five antibiotic molecules used were detected by confronting two methods: the Galesloot-Hassing method which, even though specific for the detection of penicillin in milk, is officially used for the detection of antibiotic residues in general; and the M. luteus paper disk assay, which uses M. luteus ATCC 9341 as test microorganism. The obtained results show that withdrawal times for the assayed molecules are longer than those declared and that M. luteus is more efficient for the detection of kanamycin residues. PMID- 2260793 TI - Presence and assessment of xenobiotic substances in milk and dairy products. AB - The presence of some xenobiotics such as toxic metals, PCBs, pesticides and micotoxins in both human and cow milk as well as in dairy products is evaluated on the basis of currently available data. The problems hindering a thorough risk assessment for the said toxicants are highlighted. As regards elements, the results of a study carried out on three different classes of products, namely, bulk milk from various regions of Italy, milk from one particular farm and several types of cheese available to the public at large, are reported and discussed. Quantitative determinations of Cd, Cr, Cu, Pb and Zn have been carried out by means of graphite furnace absorption spectrometry. PMID- 2260794 TI - [Research in homeopathy: data, problems and prospects]. AB - In the recent years the interest for the therapeutic use of exogenous and endogenous natural compounds, that are also employed at very low dosage, is growing up. In this context, an important role is played by homoeopathic medicine, which is involving increasing number of physicians and researchers, besides the common people. Here a critical approach to the problem of homoeopathy theory and research is attempted. The traditional concepts of the homoeopathy are challenged with the modern knowledge arising from basic and applied research. It is shown that at least a part of these concepts may find a good correspondence into the modern physiopathology. However, a number of problems, both of biological-biomedical and of practical nature remain unresolved. Moreover, any explanation of the effect of extremely diluted drugs is still hypothetical. In the second part of the work, laboratory investigations regarding the test of the homoeopathic drugs and of ultra-low doses of various substances in several experimental models are reviewed. Even if the evidence is far from to be conclusive, a number of studies showed that compounds, that are prepared and diluted according to the methods of the homoeopathic medicine, may exhibit specific stimulatory or inhibitory activities in selected experimental systems. PMID- 2260795 TI - Cocaine misuse in selected areas: Rome. AB - Dramatic increases in seizures of cocaine and, perhaps, in its use, are recording in Italy and in many European Countries. This should mean that heavy health problems have to be expected in a middle time (3-4 years), as already in USA where there is spreading of clinically relevant in-patients. The most cocaine users form the unseen part of the iceberg, so it is difficult to contact with it and to verify in extent. We report data, observations and comments on the suitability of the used "Snowball" sampling technique and, mostly, on its supplementary perspectives. This research was carried out in Rome area (September December 1987) in the frame of the first pilot multi-center study, promoted by the Commission of the European Communities, on cocaine prevalence and incidence (Munich, Rome and Rotterdam). Results about the patterns and the characters of the 83 questioned users random selected (according to "Snowball" sampling technique), 32 females and 51 males (from 25 to 51 years), are reported. Some peculiar points emerged, as the differences by sex referred to: educational level (less than 50% of the males primary/middle school, greater than 70% of the females high school/university); civil status (almost 50% of the males are single, less than 20% of the females live with partner); median length of time of use (males 8 years, females 6 years); referred cocaine amount weekly used (1-7 grams); associations with other abuse substances (50% with alcohol); drug related problems (police, work, family); tendency to start use long before (teen-agers too) and to increase it with time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260796 TI - [Toxicology of ozone and other photo-oxidants]. AB - The occurrence of photochemical oxidants ("photochemical smog") in Europe in increasingly taken into account not only with regard to forest decline, but also to human health. One of the main components of the complex mixture of individual components and also a primary bioindicator is ozone. Regarding ozone concentrations in the environment the review presents the general biological effects of ozone, results of animal experiments and observation in man. PMID- 2260797 TI - [Telemetric surveys in plant pathology and for taking the census of ungulates]. AB - Two new applications of the remote sensing techniques in the territory management which make use of a thermal scanner, are described here: the first concerned with the vegetal pathology field and the second with the big game censusing the Castelporziano farm. The former constitutes an improvement of the usual techniques either for its quick performance or for being an uncurrent intervention on plants, the latter allows to realize censuses also in thickly bushy or woody lands, where the usual methods of counting "at sight", besides to need a large staff are not much reliable. PMID- 2260799 TI - [Paraneoplastic skin diseases]. PMID- 2260798 TI - [The spectral model for characterizing gaseous pollutants in the atmosphere]. AB - Following Tukey's indications, the Authors propose the spectral model for the analysis of the temporal series related to the main pollutants of the atmosphere. In the paper the mathematical method's development is pointed out and its theoretical bases are emphasized, in particular about the basic passages; the formulas used in practice are no. (5), (6), (7) and (8). To exemplify the spectrum evaluation, the trends of the carbon monoxide (CO), relative to the summer and winter periods, are reported in frequency. PMID- 2260800 TI - [Acquired paraneoplastic hypertrichosis lanuginosa associated with scleroderma]. AB - Acquired hypertrichosis lanuginosa is universally recognized as an individual disease and seldom reported as a genuine paraneoplastic manifestation. We report the case of a 30-year old woman with acquired hypertrichosis lanuginosa. Due to the finding of a cervical lymph node metastasis, she was investigated for an internal neoplasm, but the original tumour could not be found by the usual methods. A bronchogenic carcinoma was discovered at autopsy. Beside hypertrichosis, this patient had other disorders not described in the literature as associated with that disease, viz.: progressive systemic scleroderma, fissured and hyperpigmented tongue, thrombocytopenia, galactorrhoea, axillary and pubic alopecia and overcurvature of toe nails. A review of similar cases in the literature provided clinical arguments in favour of the hormonal origin of this paraneoplastic hypertrichosis. PMID- 2260801 TI - [Cicatricial pemphigoid disclosed by superficial desquamative gingivitis. Clinical and immuno-electron microscopic study of a case]. AB - Six months before consulting, a 71-year old man developed buccal and genital erosions which gradually became worse. Physical examination showed signs of superficial desquamative gingivitis, wide erosions on the bony palate, erythemato erosive balanoposthitis and 7 bullae or skin erosions on the upper part of the back. At histopathological examination of a cutaneous bulla there was dermoepidermal cleavage and an inflammatory infiltrate without eosinophils. At direct immunofluorescence, linear deposits of IgG and C3 were present along the basement membrane. A search for anti-skin autoantibodies was negative at indirect immunofluorescence but positive at immunoblotting (240 Kd band). The cicatricial pemphigoid was treated with dapsone alone in doses of 100 mg/day. Treatment was continued for 6 months, resulting in complete cure of the mucosal and cutaneous lesions. An immunoelectromicroscopic study, performed according to the technique described by Prost et al., on a fragment of skin from around the bullae, showed deposits of granular IgG in the lamina lucida and the lamina densa and deposits of C3 in the lamina densa. This case of cicatricial pemphigoid exhibited 3 features which are not usually found in bullous pemphigoid. Clinically, the buccal lesions were located on the gums and on the hard palate, i.e. where the mucosa adheres to the underlying bone through the periosteum. This location is habitual in cicatricial pemphigoid and differs from that of the bullous pemphigoid lesions which affect the free mucosa lining the cheeks and the soft palate. Treatment with dapsone was dramatically successful in our patient whose lesions disappeared in 6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2260802 TI - [Acquired epidermolysis bullosa. Current state of knowledge]. PMID- 2260803 TI - [A case of lepromatous leprosy inoculated by tattooing]. PMID- 2260804 TI - [A picture of epidermal necrolysis after hepatic allograft. Etiologic aspects]. PMID- 2260805 TI - [Malherbe's anetoderma tumor]. PMID- 2260806 TI - [What is your diagnosis? Linear porokeratosis]. PMID- 2260807 TI - [Eczema caused by contact with sesquiterpene lactones of plants]. PMID- 2260808 TI - [Management of a case of non specific vaginitis]. PMID- 2260809 TI - [Beta 2-microglobulin: structure, function, metabolism and changes in diseases]. PMID- 2260810 TI - Computers in medicine. PMID- 2260811 TI - New waves, new problems--use of CD-ROM MEDLINE in the Medical Library of the National University of Singapore. AB - In the rapid development of optical disc technology, compact disc read-only memory (CD-ROM) is gaining popularity as a reference tool. The National University of Singapore Medical Library (NUSML) is the first special library of the University Library System to introduce CD-ROM technology by setting up of the MEDLINE on CD-ROM system to complement its reference and information services since February 1989. The experiences of the Library is setting up the system and feedback obtained from end users through a questionnaire survey are presented in this paper. The success of the implementation of the new services has also given rise to new problems which have implications on library user education programmes, manpower planning, collection development and system security. PMID- 2260812 TI - Application of computers in clinics in Singapore: status and doctors' perceptions. AB - A survey of 67 private clinics in Singapore indicates a positive trend towards use of computer-based information systems for administrative and medical applications. The computerised clinics are generally large in terms of number of staff and number of patients, and have been in operation for 3 to 15 years. Specialist clinics have a greater tendency to use computers. The widely used applications in clinics with computers are word processing, accounting, database, medical billing, drugs inventory, laboratory billing and reporting, medical records tracking, and prescription processing. Clinics with computers find: (1) software are generally suitable, (2) objectives of computerisation have been generally achieved, (3) a slight increase in operating costs, (4) a slight increase in staff productivity, and (5) satisfactory vendor support. The responding doctors rate their knowledge of computers from average to poor. Doctors with computers in their clinics hold the perception that: (1) computers can adequately support clinic operations, (2) computer systems are reliable, (3) a genuine need exists for computers in clinics, (4) computers are useful as research tools, and (5) legal and ethical constraints may inhibit use of computers in medical applications. Further analysis of the data has identified some interesting correlations among clinic variables and among doctors' perception variables. PMID- 2260813 TI - Craniofacial osseous landmark determination from stereo computer tomography reconstructions. AB - The accurate and reproducible determination of the three dimensional (3D) co ordinate positions of anatomical landmarks from computer tomography (CT) images has been limited even though potentially the data have been available for several years. This paper describes a method of acquisition of osseous landmark positions using an off-line computing technique based on multiple stereo images of 3D CT reconstructions. The use of stereo pairs greatly enhances the consistent identification of osseous landmarks. Further, the technique is of particular value where access to the CT scanner is restricted due to heavy clinical demand and separate high quality graphics facilities are unavailable. Osseous landmark position data were determined for dried skulls and patients with craniofacial conditions. Accuracies of the order 1.7mm (median) were obtained. These results encourage the use of the technique for acquisition of landmark positions for the study of the craniofacial complex in three dimensions. PMID- 2260814 TI - Derivation of flow-volume and time domain spirometric indices by digitisation of volume-time spirograms. AB - All the information regarding the forced expiratory manoeuvre are contained in the simple volume-time spirogram. Flow-volume and time-domain indices could be derived by digitising the volume-time spirogram. This paper describes an electronic means of digitising the spirogram and demonstrates its capability in deriving flow-volume and time-domain spirometric indices. The spirograms of 118 granite quarry workers were digitised using an electronic digitising pen. The volume and time data are stored in a micro-computer and a programme written in dBASEIII Plus is used to smoothen and derive the standard volume-time, flow volume and time domain indices. There was good agreement between digitised and hand-read values (intraclass correlation coefficients, rI, greater than 0.9) for the forced expiratory flow in one second (FEV1) and forced vital capacity (FVC) irrespective of the pulmonary status. There was a small but statistically significant difference between digitised and hand-read FEV1 for those with normal and restrictive pulmonary function groups (-115 ml/sec and 19 ml/sec respectively). There was however, no evidence of systematic bias between the two methods. The technique described herein provides a rapid and accurate means for deriving flow-volume and time domain indices from a volume-time spirogram. It also provides the opportunity to reanalyse previously collected volume-time spirograms and allow for the assessment of small airways function of these subjects using newer flow-volume and time domain indices. PMID- 2260815 TI - Computer assisted instruction for autistic children. AB - Since the beginning of 1980, Computer-Assisted-Instruction (CAI) has been used systematically in special education. The use of computers in the treatment of autistic children is highly controversial and emotional among parents and professionals. Fears of reinforcing autistic withdrawal are often mixed with insecurity and dislike of new technologies. On the other hand, positive effects of CAI on learning and behaviour are reported by parents and published as single case studies. The following paper relates perception, motivation, communication and behaviour--characteristics of autistic children to features of computer assisted learning. Preliminary findings support the benefit of the use of computer-technology for the management of behaviour and learning of autistic children. In 12 autistics, video-taped evaluations showed higher enthusiasm ratings in computer-sessions than personal instruction sessions. Single case studies demonstrated a positive influence of CAI on autistic children's behaviour problems (e.g. avoidance of eye contact, echolalia) as well as improved spontaneous communication and better learning of academics. PMID- 2260816 TI - Information networks and their impact upon medicine. AB - There is an information explosion and geometric growth of knowledge in medicine. The individual physician finds himself having great difficulty coping with this ever increasing knowledge base. The recognition of a gap in such knowledge; while frustrating, may also have a direct impact upon patient care. Computer technology, information retrieval modalities, and teleprocessing between remote locations has been viewed as a partial solution to this issue. Microcomputers and their associated elements are able to be used as information retrieval devices tapping into vast reservoirs of data and information on all aspects of medicine. Physicians faced with this new technology generally have little or no training, experience or understanding of how best to harness the power of computers to meet their individual practice requirements. This article provides a basic overview of those computer concepts that relate specifically to information retrieval from large data bases to individual physician's offices, regardless of their location. The article explores the specific hardware and software components that are required for effective linkage into a computer based information network for medicine. The article concludes with an overview of the work done by the American Academy of Dermatology in this area to satisfy informational needs of its members in coping with the ever increasing knowledge base of medicine. PMID- 2260817 TI - Emerging technologies in the field of healthcare: enhancing the interface to the medical professional. AB - This paper reviews the latest technology either available or currently under development which will enhance the medical professional's ability to interface computer systems. This technology includes bar-coding, graphics, intelligent workstation, and expert system. Whenever possible, examples are given to illustrate the technology. PMID- 2260818 TI - Harnessing information technology to revolutionise teaching, research and consultative service in health statistics. AB - Computers have traditionally been associated with health statistics because of the need to manage, process and analyse data. Over the last two years, the Division of Biostatistics and Health Informatics of the Department of Community, Occupational and Family Medicine at the National University of Singapore has been actively looking into ways in which informatics and telematics could be usefully applied to teaching and research in health statistics and in the provision of a statistical information service. This paper describes three projects, originating from the National University of Singapore, which provide an effective demonstration of the application of modern technology to an age-old discipline. PMID- 2260819 TI - A review of adverse effects on reproduction amongst female computer terminal workers. AB - It has been suggested that pregnant women working with computer terminals and visual display unit (VDUs) could be at an increased risk of having a spontaneous abortion or giving birth to children with congenital defects. This has led to apprehensions and worry among computer operators. This review attempts to evaluate some of the recent studies and provide some current knowledge on the possible reproductive hazard of VDUs. According to current scientific knowledge, the use of computer terminals during pregnancy does not by itself, lead to increased risks of adverse reproductive effects. PMID- 2260820 TI - MediNet: Singapore's nationwide medical network. AB - MediNet is Singapore's nationwide computer network for the medical and health care community. This paper presents the case for MediNet and discusses the five high-priority applications which would be implemented by 1993. These 5 pilot applications focus on the processing of claims in hospital bills, electronic procurement of medical and surgical supplies, the transmission of notifications to government agencies, a national patient master index and access to local and foreign databases. MediNet will be able to link the computer systems of all participants in the healthcare delivery system. These include the Ministry of Health, Central Provident Fund (CPF) Board, government, restructured and private hospitals and general practice clinics. By connecting their computers (personal computers, minicomputers and mainframes) to MediNet, these organisations will be able to communicate, exchange data and access common applications on the network. PMID- 2260821 TI - Ministry of Health computerisation programme. AB - The purpose of the paper is to give the readers an idea of the state of computerisation in the Ministry of Health, Singapore and to highlight some of the benefits of computerisation. The Ministry employs a wide range of computer systems from portable microcomputers, point-of-sale microcomputers, supermicros, minicomputers to mainframe computer. What are the roles of these computers? Why and how are they interconnected? Carry on reading if these questions are appealing to you. PMID- 2260822 TI - Hospital based drug allergy register in Singapore. PMID- 2260823 TI - Fuzzy Logic for medical expert systems. AB - The use of linguistic approximation enables knowledge to be represented in a more meaningful way and this is especially important in medical domain as it involves a lot of subjective decision making; Fuzzy Logic, introduced by Zadeh, has the ability to represent this imprecise expression. In this paper, an alternative approach of Fuzzy Logic in handling the approximate reasoning in expert systems will be described. The approach does not use the General Modus Ponen on the compositional rule of inference, but instead it uses a collection of rules to specify the properties of the inference (in making decision). An example of medical domain is described as its application. PMID- 2260824 TI - Computer applications in dermatology. AB - Advances in computer technology both in hardwares and softwares has stimulated the proliferation of the use of computers in dermatology. The computers enable the voluminous medical literature and records to be compiled and accessed readily. Information technology enables dermatologists to conduct literature searches efficiently and helps in the management of patients. The information compiled in the computers as databases together with its capability to handle complex statistical analysis also enables dermatologists and computer scientists to develop expert systems to assist the dermatologist in the diagnosis and prognostication of diseases and to predict disease trends. Computers have also allowed dermatologists to assess visual images objectively, making it possible to study treatment response more accurately. PMID- 2260825 TI - A computer system for contact dermatitis: graphical representation of data. AB - An overview is given of the computer applications we have developed over the last twelve years in the field of contact dermatitis. The dissemination of exposure lists to sensitised individuals and the development of a knowledge-based system are mentioned only briefly. Priority here is given to the explanation of the graphical representation of the patient data collected since 1978 on 12,000 patients referred to three contact dermatitis units. More than a hundred parameters of each patient have been collected in a database. Several graphs are given of these data and are discussed in detail. PMID- 2260826 TI - Computer applications in orthopaedics. AB - With the rapid developments in microprocessors, the widespread availability of computers has brought about broad applications in the field of orthopaedics. The present technology enables large quantities of data to be logically processed in a very short span of time. This has led to the development of information management database systems where relevant medical information may be retrieved very quickly and effectively. The analytical power of the computer has also been utilised in expert systems to assist in clinical-decision making process. Computer graphics have revolutionised the visualisation of physical features of internal and external body parts, providing new and improved modalities of diagnosis. In some centres, surgical planning and rehearsals are already being carried out at the computer terminal with the use of animation and computer graphics. Computer technology has also played an active role in the field of prosthetics and rehabilitation. Intelligent robotic systems and microprocessor with functional neuromuscular stimulation have been applied to benefit, and in some cases restore some motor functions to the physically disabled. With more collaboration between engineers, scientists and the medical community, several prototypes of computer-controlled prostheses and prosthesis designed and manufactured by Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) technology are available today to assist the amputees in their daily living and ambulatory activities. PMID- 2260827 TI - Computer-Aided Design and Computer-Aided Manufacture (CAD-CAM) applications in cosmetic below-elbow prostheses. AB - Computer-Aided Design and Computer-Aided Manufacture (CAD/CAM) techniques, though often technologically associated with engineering and applied sciences, has opened new horizons in the medical field. In CAD, a product is first geometrically modelled in three dimensions in a computer and it can be viewed and examined from any direction. This model can then be used for many downstream applications such as manufacturing and analysis. In CAM, numerically controlled machining processes are used for cutting out a prosthetic device of the hand for prosthesis. The paper aims at establishing the basis of using CAD/CAM techniques in prostheses in particular, a review of our present work done in the area of below-elbow prostheses using CAD/CAM. A laser scanning device has been used to capture the geometry of human hands. The algorithm used in processing the images is discussed. The processed 3D data file is then interfaced with a CAD modeller where reconstruction, mirroring, scaling, etc., can be performed. The resultant CAD model is then passed on to CAM, which concentrates purely on producing a "positive core" mould for moulding the prosthetic device. PMID- 2260828 TI - Principles and applications of Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) technology in orthopaedics. AB - The principles involved in Computer-Aided Design (CAD) and Computer-Aided Manufacturing (CAM) technology is presented in this article. It also highlights the current advances and capability of this technology. Application of the CAD/CAM technology in orthopaedics is relatively new. Three broad areas of applications can be defined: (1) three-dimensional reconstructions of skeletal structure based on any of the imaging technique, i.e. CT scan, MRI or X-ray, to analyse, simulate, design and evaluate orthopaedic procedures without having to actually perform the surgery; (2) the production of plastic or wax models for surgeons to have global impressions and understanding of complex cases of bone and joint disorders and the possibility of using the physical models as templates to sculpt allograft pre-operatively; and (3) to design and manufacture geometrically optimal standard and customised implants. CAD/CAM technology is also rapidly developing in the field of prosthetics, orthotics and orthopaedics footwear. The advantages offered include shorter delivery time, more consistent design, quantifiable rectification and "modern" or remote manufacturing. Apart from these applied usage, the CAD/CAM technology is also an effective tool for education and training. The application of CAD/CAM technology in orthopaedics and its related fields has been shown to have tremendous potential, but may appear to be too esoteric, complex and costly at the present moment. However, with improved generality, simplicity and cost-effectiveness of the system, it will become more practical. PMID- 2260829 TI - Computers in radiotherapy. AB - Radiotherapy is one of the earliest fields in Medicine in which computers have made an inroad. The main uses of computers, which include treatment planning, dose calculations, localisation of tumours, verification of patient setups and radiation beam data acquisition, are highlighted in this paper. It is believed that a modern Radiotherapy department cannot function optimally without some form of computing facilities. With advances made in dose calculation algorithms, and in high performance computers, it is expected that the target of 3% accuracy dose calculations can be achieved in treatment planning. PMID- 2260830 TI - Applications of computer technology in dentistry. AB - Technological advances in industrial manufacturing have contributed to improvement in productivity and quality of dental care. However, computer technology has also been exploited but not to the same extent as other forms of technology. This paper examines computer applications that have been utilised by various groups of dental professionals in the provision of dental care and in dental education. The benefits derived from existing applications and future possibilities are seen in the following fields. In practice management, besides the usual collecting, sorting and searching of data, productivity and efficiency are greatly increased through computer appointments, recall and practice analysis programmes. In patient education, the use of computer graphics has enabled simulation of cosmetic changes to be presented to the patient with before and after possibilities. Dental education and communications have moved forward with the introduction of Computer Assisted Instruction programmes, and bibliographic databases including electronic transmission of Continuing Dental Education which are now easily available. In the field of Diagnostics and Treatment planning, the advent of CAD-CAM has made possible the use of cutting devices which mills a 3 dimensional model of the designed restoration from solid blocks of gold. Computer applications has also been used in forensic dentistry where identification systems describe tooth conditions and other oral characteristics besides automated screening and matching of antemortem databases. PMID- 2260831 TI - Use of computers in quality assurance of laboratory testing. AB - Implementation of comprehensive internal quality control programmes and participation in external quality assessment schemes to monitor analytical performance of laboratory tests have been widely accepted as an essential and integral part of good laboratory practice. As these programmes involve a great deal of repetitive statistical calculations and graphic presentation of data on quality control materials, many laboratories and practically all organisers of inter-laboratory quality assessment schemes increasingly rely on computers to handle the burdensome processing of data and to provide timely feedback in a manner that is easily understood and readily interpreted by analytical staff. However, in spite of the best effort to ensure reliable analytical performance, spurious and misleading results can still occur as a result of non-analytical errors which are not readily detected by methods designed to monitor the quality of analytical process. The use of sophisticated computer system has enabled our laboratory to check for the existence of some of these errors. This paper describes the application of computers in a variety of internal and external quality assessment programmes and demonstrates the usefulness of retrieving patients' cumulative test results and at the same time performing delta or percentage difference checks on such data in the detection of non-analytical errors and unexpected variations in results. The role of the computer in minimising transcription errors, reducing turn-around time of testing and reporting, as well as improving the quality of laboratory reports is also mentioned. PMID- 2260832 TI - The computerisation of scientific services. AB - A full computerised laboratory information management system has been developed in the Department of Scientific Services. The system manages the acquisition and flow of laboratory data. A novel automated reporting procedure has been developed to generate customised laboratory reports. Based on the workload values of laboratory tests, the system integrates the laboratory data with management information to provide rapid and reliable productivity measurement and cost and pricing computations. PMID- 2260833 TI - Computer application in a general practice. AB - Computer application in General Practice has improved the standard of healthcare. Computers have been used in the clinic for general administration and accounting. A Clinic Management System in addition can be used in most of the functions required in the running of a clinic. It will be able to generate useful data to help the doctors make sound decisions based on valid, up-to-date information. Communications and accessing of medical databases can be made available with a central network such as MediNet. There are currently no well developed medical record management systems suitable enough for implementation in general practice. Computerisation of the general practice will require careful planning and gradual implementation using a reliable application software backed by good support from the original developer. Commitment to continued research and development of the software will ensure that the implemented system will not be outdated. PMID- 2260834 TI - The computer in group practice--a British experience. AB - This paper describes the author's work experience using a computer in consultation in a large computerised academic practice in Manchester, U.K. Prescribing, preventive health screening and recall, the use of disease registers and billing are common medical applications with proven usefulness. System implementation however is not without problems; the capital cost to the practice, decisions regarding hard and software, the conversion of written to computerised records, access and confidentiality and staff training are issues to be resolved. Computer use may also extend consultation and staff time. It is hoped that this experience will help doctors intending to computerise to focus on applications and implementation issue. PMID- 2260835 TI - Computer graphics in medical illustration. AB - The advent of powerful personal computers (PC) has revolutionised the production of graphic illustrations in the various disciplines of medicine. This paper reviews the current hardware devices and software programmes available in the personal computer market for the generation, processing and production of graphic output in medical illustration for the purposes of teaching and presentation. A low-cost method of generating high quality presentation slides on IBM-PC based systems is also outlined. PMID- 2260836 TI - The integration of knowledge through interactive Computer-Enhanced Learning in medicine. AB - Rapid advances in Information Technology in recent years have provided powerful computers and software that can be innovatively applied to create powerful pedagogical courseware that go beyond what precursors like the PLATO project could do on the mainframes of yesteryear. This article focusses on the research and development that we have carried out which is applicable to the whole area of education (including medical education). It introduces the elements of hypertext, hypermedia and the pedagogical user interface. It illustrates the principles necessary for the communication of conceptual, functional and structural knowledge. It emphasises the key aspect of mastery of Information Technology necessary for a new dimension in Computer-Enhanced Learning that will be of relevance to the Information Society of the 21st century. PMID- 2260837 TI - The effective learning of spatio temporal concepts of human structure. AB - The recent availability of increasingly powerful and user friendly computers is making a noticeable impact in the field of medical education. Over the past year, the power of the computer is being harnessed here in the field of anatomy to enable medical and dental students to learn the subject more effectively. Machines with excellent graphics, text and animation capabilities have made it possible to allow students to comprehend structural complexity as seen in gross anatomy or, temporal alterations of structure as seen in embryology by the use of computer based, tutorial style or self paced interactive style of learning. Positive student response to sample learning packages has encouraged the undertaking of courseware development for future use at computer workstations. PMID- 2260838 TI - Hypertext-based enhancement of medical and dental undergraduate learning. AB - The use of the microcomputer in medical education began about 1977. Since then man computer-assisted learning packages have been developed for preclinical and clinical subjects. The experiences of the authors with the Macintosh microcomputer in the development of courseware and tutorware on some aspects of Anatomy in the Department of Anatomy of the National University of Singapore are shared in the present paper. It describes how textual and instructive material can be prepared along with graphics support using a software called HYPERCARD (Apple Inc.). Elementary levels of animation can also be achieved. In this way it illustrates how a study of Anatomy, for example, can be made using the computer to "dissect" the human body. PMID- 2260839 TI - Skeletal maturity in Belgian youths assessed by the Tanner-Whitehouse method (TW2). AB - Reference data for skeletal maturity (TW2 method) of the hand and wrist are provided for large representative samples of Belgian boys and girls. The sample of Belgian boys consisted of 21,174 boys aged 12 to 20 years studied in a nationwide cross-sectional and longitudinal study on the physical fitness of secondary schoolboys (1969-1974). The girls' sample consisted of 9698 6-19-year old Flemish girls studied cross-sectionally (1979-1980). Both samples were multi stage stratified cluster samples of entire school classes. All skeletal maturity assessments of the boys were made by the same observer (GB). His estimations agreed quite closely with those of the originators of the method. The skeletal age assessments of the girls were made by two observers trained by GB. Both observers showed high intraobserver reliability after training, and during the assessments. Moreover their ratings compared favourably with those of GB and the originators of the method. Smoothed percentile curves of the maturity scores (TW2 20 bone, RUS and CARP scores) were calculated by means of cubic splines using a stepwise regression procedure for the selection of suitable knots. In the boys, the TW2 scores (20 bone and RUS) increase linearly between 12 and 14.5 years of age, slow down for a while, and then increase again, while the CARP scores increase linearly between 12 and 15 years of age. In girls, the 20-bone maturity scores increase nearly linearly from 6 through 9.5 years of age, accelerate until 11.0 years followed by a smaller increase; RUS scores increase curvilinearly from 6 years of age onwards; and Carp scores increase almost linearly between 6.0 and 12.5 years of age. Belgian boys are advanced in RUS scores but are delayed for the carpal bones as compared with the British standards. The Belgian girls show advancement for both scales as compared with the British reference data. The skeletal maturation of youths from several other continental European countries corresponds more closely with the Belgian than with the British data. The reference data presented herein most probably provide suitable standards for youths of West-European countries. PMID- 2260840 TI - Reproductive versus chronologic age as a predictor of low birth weight, preterm delivery and intrauterine growth retardation in primiparous women. AB - The effect of reproductive age (chronologic age at conception minus menarcheal age) and chronologic age on the risks of low birth weight, preterm delivery and intrauterine growth retardation were studied in 1198 primiparous women whose pregnancies ended in singleton live births at Yale-New Haven Hospital, 1980-1982. After adjustment for maternal race and other important confounding variables, neither young reproductive age (less than 8 years) nor young chronologic age (less than 20 years) were strongly related to any of the reproductive outcomes. Older chronologic age (greater than 29 years) was also not strongly related to any of these outcomes, but older reproductive age (greater than 15 years) was moderately associated with low birth weight (OR 1.9; 95% CI 0.9, 3.8) after adjusting for maternal race, religion and smoking status. In addition, extremely young reproductive age (less than 2 years) appeared to be associated with an increased risk of preterm delivery (OR 3.1; 95% CI 0.7, 14.6), but our sample was too small to adjust for confounding factors in this group of women. Reproductive age appears to reflect extremes in menarcheal age, whereas chronologic age does not, and this association may account for any relationship between reproductive age and pregnancy risk in primiparous women. PMID- 2260841 TI - Age and sex differences in bone density of the second metacarpal in its midshaft cross-section. AB - On the basis of the midshaft cross-section of the second metacarpal in 102 male and 96 female Japanese, aged 30 to 98 years, age- and sex-related differences of bone mass and density are examined. Bone mass and density are almost always greater in males than in females. Cortical mass and apparent bone density decrease gradually with age after 45 years of age in both sexes. The decreasing rate is about twice as great in females as in males. The sex difference increases gradually with age, especially after the sixth decade. However, true bone density remains almost constant, regardless of age, until the seventh decade in both sexes. The maximum density layer is more deeply located at the radial side than at the ulnar, and also more so in males than in females, corresponding to the differences in cortical thickness. The relative depth of this layer to the bone width is about 15% at the radial side and 12% at the ulnar in males and about 12% and 10% at each side in females, respectively. PMID- 2260842 TI - Short-term variations in stature growth in Ethiopian and English children. AB - Two groups of young children, one in Addis Ababa and one in Oxford, were measured every calendar month for 6 months. Changes in their stature variability, as evidenced by increasing measurement interval length, are here compared. There is evidence for substantially greater variability in the Addis Ababa children. When the variability is expressed as coefficients of variation both groups show a marked decline with interval length, presumably as constant and additive components of variation become proportionally less important as the mean increases. One constant element is identified in the Addis Ababa children, since a single subtraction from all interval coefficients greater than two months produces the same CV. It is concluded that this probably represents the homeostatic cycle of catch-up growth in this group of children. PMID- 2260843 TI - Marital correlation for anthropometric characteristics in Brazilian Indians. AB - A total of 336 couples from 10 villages of three Brazilian Indian tribes was studied in relation to 15 anthropometric characteristics. Correlation coefficients between husband and wife were generally positive, none of the negative ones reaching a probability level of 1% or less. Thirteen correlations attained this level, but none of the traits behaved similarly in the three tribes. Height adjustment taking into consideration the correlation between mates for age did not much alter the correlation coefficients, but a larger influence was observed after allowance for temporal effects. A significant pair of canonical variables was obtained considering sitting height and leg length, but factors related to facial and bone form, extracted through principal-components analysis, yielded correlations insignificantly different from zero. PMID- 2260844 TI - Motor performance during adolescence and age thirty as related to age at peak height velocity. AB - Relationships between motor performance, as measured by various fitness tests, and age at peak height velocity have been studied in a sample of 173 Flemish boys, measured yearly between +/- 13 and +/- 18 years and again as adults at 30 years of age. In addition to correlation studies, comparisons were made between boys with an early, average and late age at peak height velocity. To summarize the successive measurements during adolescence, a longitudinal principal component analysis was carried out. The first component can be interpreted as an average percentile level component. During adolescence, three performance tasks, namely speed of limb movement, explosive strength and static strength, are negatively related to age at peak height velocity; thus early maturers performed significantly better than late maturers. However, between late adolescence and adulthood, a cross-over of the average distance curves between 18 and 30 years of age was noted for almost all motor tasks. The late maturers not only caught up the early maturers, but there were significant differences for explosive strength and functional strength in favour of late maturers. In order to predict performance in adulthood from measures during adolescence, the following hypothesis is suggested: the best results at adulthood are obtained by those men who were already good performers during adolescence and who were late maturers, while the worst results are obtained by poor performers during adolescence who were early maturers. PMID- 2260845 TI - Daily measurements of the heights of two children from June 1984 to May 1985. AB - Two children, a sister and a younger brother, were measured with regard to stature, head and neck height, iliospinal height, and trunk length, every morning and evening for one year. They were 7.5 years old and 6.6 years old, respectively, on the first day of the investigation. In both children, stature and trunk length, but not the other dimensions, were longer in the morning and shorter in the evening. Almost all the year's statural elongation was due to lower limb elongation, but there was a sharp upward turn in April-May which resulted from an increase in trunk length. The head and neck height curves were flat throughout the year. PMID- 2260846 TI - A relationship between bioelectrical impedance and total body water in young adults. AB - Total body water was measured using the stable isotope H2(18)O in 14 young adults. Body resistance was assessed using a tetrapolar technique using a Holtain body-composition analyzer. Total body water was highly correlated (r = 0.96; p less than 0.001) with height2/resistance. The inclusion of body weight in the prediction equation reduced the standard error of estimate from 1.9 to 1.51. Bioelectrical resistance can be used to assess other body-composition parameters such as fat-free mass and fat mass, but this use involves a number of assumptions which may confound the relationship. We suggest that the measurement of bioelectrical impedance may, however, have a role in the estimation of total body water. PMID- 2260847 TI - Large-scale neurocognitive networks and distributed processing for attention, language, and memory. AB - Cognition and comportment are subserved by interconnected neural networks that allow high-level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain-behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function. PMID- 2260848 TI - Impairment of sequences of memory-guided saccades after supplementary motor area lesions. AB - Different paradigms of saccades were recorded electro-oculographically in 2 patients with infarction affecting the left supplementary motor area. Saccades made toward visual targets (visually-guided saccades) or away from them (antisaccades) were normal in both patients. Memory-guided saccades, made to the remembered position of a flash occurring 2 seconds before, were preserved in 1 patient and only slightly impaired in the other. However, sequences of two or three memory-guided saccades were severely impaired in both patients. It has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements. Our data suggest that this area plays a similar role in the control of sequential eye movements. PMID- 2260849 TI - Quadriceps myopathy: forme fruste of Becker muscular dystrophy. AB - We examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles. All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as "patchy" or discontinuous immunostaining at the surface membrane of the muscle fibers. One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy. We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy. PMID- 2260850 TI - Noninvasive detection of occlusive disease of the carotid siphon and middle cerebral artery. AB - Recently, transcranial Doppler sonography has been introduced into clinical practice for noninvasive investigation of the large intracranial arteries. To determine its accuracy for detection of stenosing or occluding lesions, 133 consecutive patients were studied by both transcranial Doppler sonography and selective cerebral arteriography. Statistical analysis of findings was done separately for various arterial segments. High values for sensitivity and specificity were found for detecting obstruction of the carotid siphon and main stem of the middle cerebral artery. Diagnostic reliability of transcranial Doppler sonography was also confirmed by the calculation of a chance-corrected measure of agreement (kappa), which was close to + 1 in all subanalyses. Transcranial Doppler sonography seems to be a valuable tool for noninvasive detection of intracranial lesions of the middle cerebral artery and carotid siphon. PMID- 2260851 TI - Mild senile dementia of the Alzheimer type: 3. Longitudinal and cross-sectional assessment. AB - Sixty-six subjects diagnosed by validated criteria as having senile dementia of the Alzheimer type (SDAT) were assessed with clinical measures commonly used to study dementia. The severity of the SDAT was mild in 24, moderate in 24, and severe in 18. The data from these three groups in a cross-sectional study were compared with results in our earlier study of 43 subjects enrolled with mild SDAT and followed longitudinally. We concluded that the cross-sectional method underestimates the severity of progression as indicated by some of the clinical measures. Additionally, the 24 new subjects with mild SDAT were assessed longitudinally. This replication study confirmed our earlier conclusions that four of six clinical measures showed similar patterns over time and were useful throughout the study, global measures being more informative than brief individual measures with ceiling or floor effects. PMID- 2260852 TI - Eyelid movements before and after botulinum therapy in patients with lid spasm. AB - Quantitative analysis of lid motility is presented for 4 individuals with hemifacial spasm and 1 with Meige's syndrome. The data were obtained, by means of a magnetic search coil technique, prior to and 1 week after injection of botulinum toxin into the orbicularis oculi muscle. Before treatment, the peak velocity of blink-related lid lowering and lid raising was slower than normal, yet lid saccades were normal. After botulinum treatment, significant decreases occurred in (1) the amplitude of blinks and lid saccades, and (2) the peak velocity of the blink down-phase. Botulinum treatment significantly alters blink lid-lowering kinematics, while saccadic lid-lowering kinematics are normal, providing further evidence that the orbicularis oculi muscle does not play a primary role in downward lid saccades. PMID- 2260853 TI - Brain pH in head injury: an image-guided 31P magnetic resonance spectroscopy study. AB - It has been suggested that brain acidosis may follow head trauma, and therapies aimed at correcting acidosis have been proposed. Direct measurements of intracellular pH, however, have thus far not been possible in clinical situations. We have studied the intracellular brain pH in 22 patients after head injury (mean Glasgow Coma Score 6.1). Patients were investigated by a combined approach of phosphorus 31 magnetic resonance spectroscopy and magnetic resonance imaging (overall examination time 50-75 min) at a mean time of 11 days after injury (36 hours to 24 days). 31P spectra were obtained in 11 patients on assisted ventilation and in 11 patients on spontaneous ventilation. These spectra were analyzed to yield the pH in the regions studied in all the patients. All pH values were in the normal or alkalotic range when compared with 6 age-matched normal controls. No differences were found between patients on assisted ventilation and patients on spontaneous ventilation. When analyzed as a group, the brain pH in the focal lesions appeared to increase in the first days, to reach a peak in the alkalotic range in the second week, and to return toward normal within 3 weeks from acute injury. Our results suggest that there is no evidence of posttraumatic intracellular brain acidosis in recent human head injury, and therefore, therapies aimed at alkalinizing brain cells need to be reconsidered. PMID- 2260854 TI - Respiratory failure and unilateral caudal brainstem infarction. AB - We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (PaCO2 62 mm Hg, PaO2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses. PMID- 2260855 TI - Elevated soluble interleukin-2 receptor levels in patients with active multiple sclerosis. AB - The level of soluble interleukin-2 receptor (sIL-2R) was quantitated with enzyme linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL 2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL-2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL-2R level may be useful in evaluating disease activity in patients with multiple sclerosis. PMID- 2260856 TI - Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti-neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration. AB - We isolated a complementary DNA clone encoding a 52-kd protein recognized by an anti-neuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti neuronal cell antibody from the patient, and its molecular weight was identical to that of antigenic proteins in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydrophilic residues, the calculated relative molecular mass was 51,238, and the predicted value of the isoelectric point was 4.99. This complementary DNA sequence and the deduced protein sequence have not been reported previously, and the sequences showed no homologies with the complimentary DNA or the amino acid sequences in the GenBank, EMBL, or NBRF databases, including the complementary DNA for a 34-kd cerebellar protein (CDR34) that is recognized by an anti-Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue, the intestine. PMID- 2260857 TI - A follow-up study of intractable seizures in childhood. AB - One hundred forty-five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset. The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age. Age of onset was significantly later (mean 5.0 +/- 0.5 yr [SEM]) in the group of children with borderline to normal intelligence. Follow-up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year. Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation. Seizure type had some effects on outcome. Children with focal atrophic brain lesions did no worse than those without definable pathology on brain-imaging studies. PMID- 2260858 TI - Evoked potential studies in neurological diagnosis and management. PMID- 2260859 TI - Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. AB - Autoantibodies that reacted with cell bodies and axon terminals of gamma aminobutyric acid (GABA)ergic neurons were present in the serum and cerebrospinal fluid in a patient with stiff-man syndrome with type I diabetes. Immunoblot experiments using this patient's serum and cerebrospinal fluid did not corroborate an earlier observation that these autoantibodies are directed against the GABAergic cytosolic enzyme, L-glutamic acid decarboxylase. While L-glutamic acid decarboxylase autoantibodies may be associated with this syndrome, they do not appear to be easily demonstrated. PMID- 2260860 TI - Extended levodopa release from a subcutaneously implanted polymer matrix in rats. AB - It is well recognized that plasma fluctuations resulting from oral levodopa therapy may cause an unstable clinical response in parkinsonian patients. We have therefore developed a slow-release polymer matrix system that can deliver levodopa continuously for extended periods of time (at least 225 days) after subcutaneous implantation in rats. Advantages of this approach include (1) the elimination of levodopa plasma fluctuations and (2) the possibility of reducing the required dose due to constant plasma levels and because the gastrointestinal tract is circumvented. The peripheral implantation of polymer systems containing levodopa, dopamine receptor agonists, or other anti-Parkinson agents may constitute a novel technology of drug delivery to improve the care of patients with Parkinson's disease. PMID- 2260861 TI - Absence of immunoreactive enzyme protein in short-chain acylcoenzyme A dehydrogenase deficiency. AB - Defects of short-chain acylcoenzyme A dehydrogenase (SCAD) may cause a severe metabolic illness in children or a lipid storage myopathy in adults. The childhood form is associated with low enzyme activity, but the synthesis of a normal-size enzyme protein in cultured skin fibroblasts. We report further biochemical studies on the original patient described with myopathic SCAD deficiency. We show an absence of enzyme protein in skeletal muscle, which both confirms the original diagnosis and suggests that the two forms of SCAD deficiency have a different molecular basis. PMID- 2260862 TI - Normal dystrophin in McLeod myopathy. AB - Dystrophin and its gene were studied in a patient with McLeod syndrome. This X linked recessive myopathy has been localized to Xp21, as has the Duchenne muscular dystrophy gene locus, which codes for dystrophin. Histopathological study of the patient's muscle showed mild subclinical myopathy. Immunological studies of dystrophin in two separate biopsy specimens and analysis of dystrophin gene DNA from a blood sample did not detect an abnormality. This suggests that the Duchenne muscular dystrophy gene, albeit close to the McLeod locus, is not involved in McLeod myopathy. PMID- 2260863 TI - Neuropathological substrate of dementia in Parkinson's disease. PMID- 2260864 TI - The electroretinogram in Alzheimer's disease. PMID- 2260865 TI - Magnetoencephalographic localization of epileptic foci. PMID- 2260866 TI - [Carcinogenicity of anticancer agents]. AB - Chemotherapeutic treatment for cancer has been successful in prolonging survival but it has also been demonstrated that survivors of cancer patients who had received chemotherapy with alkylating agents have an increased risk of second malignancies, mostly acute non-lymphatic leukemia. The purpose of this paper is to show practical problems pertaining to the development and clinical use of anticancer agents in terms of prevention of second cancers. PMID- 2260867 TI - [Autologous bone marrow transplantation in pediatric cancer]. AB - Since May 1979, 47 patients with pediatric malignancy aged 1 to 18 years (median: 7) were treated with cryopreserved autologous bone marrow transplantation (ABMT) in the department of pediatrics, National Cancer Center Hospital. The malignancies were acute non-lymphocytic leukemia (n = 8), acute lymphocytic leukemia (n = 5), osteosarcoma (n = 7), neuroblastoma (n = 6), brain tumor (n = 5), rhabdomyosarcoma (n = 4), retinoblastoma (n = 3), Ewing's sarcoma (n = 3), non-Hodgkin's lymphoma (n = 2), malignant histiocytosis (n = 1), hepatoblastoma (n = 1), malignant melanoma (n = 1) and malignant neuroepithelioma (n = 1). Conditioning regimens for solid tumors were multi-agent high-dose chemotherapy, mainly consisted of cyclophosphamide (CY) 120 mg/kg or melphalan 180mg/m2 and that for hematological malignancies were CY with fractionated total body irradiation (12 Gy). In vitro purging by 4-hydroperoxycyclophosphamide was performed in 12 leukemia patients and 5 solid tumor patients. Of the 13 patients with acute leukemia, 1 died from relapse 1 year after the unpurged marrow transplantation and 1 relapsed in the testis. Remaining 11 patients are alive in continuous complete remission with a median follow up of 30 months (range, 2 to 65 months) after transplantation. The disease-free survival rate of them was 78%. Of the 34 patients with solid tumor, 21 patients died, their cause of death were relapse in 18 and each one of infection, graft failure and brain hemorrhage. Thirteen patients are alive without disease with a median follow up of 28 months (range, 2 to 107 months) posttransplant. The longest survivor is a brain tumor girl, and there are 5 other long survivors; 2 of them are osteosarcoma and each one of rhabdomyosarcoma, Ewing's sarcoma and malignant histiocytosis. The disease free survival rate of total 34 solid tumor patients is 29%, but that of 17 patients who received ABMT in responsive and minimum tumor residue (MTR) period was 69%. These results suggest that autologous bone marrow transplantation is an effective and tolerable treatment for poor prognostic pediatric malignancies, especially for acute leukemia and such solid tumor as that in MTR state. PMID- 2260868 TI - [Present status of neuroblastoma mass screening in Japan. Neuroblastoma-Committee of the Japanese Childhood Cancer Society]. AB - In 1973, mass screening program for 6-month old infants for early detection of neuroblastoma using a VMA spot test of a urine sample was initiated in Kyoto. In 1985, nation wide mass screening was initiated throughout the entire country and the Government has given the financial support to each district. In 1988, the Government recommended the institution of mass screening by quantitative measurements of VMA, HVA and creatinine using HPLC (high performance liquid chromatography), instead of the qualitative test of VMA alone. From 1974, at the time of initiation of mass screening for neuroblastoma to the end of October, 1989, 383 cases with this tumor have been discovered throughout the screening program. Three hundreds eighty three cases (88%) of them had been registered to the Neuroblastoma Committee of the Japanese Society of Pediatric Oncology. In this paper, the mass screening program was introduced and the 337 cases with this tumor detected by 6-month old screening were analyzed their clinical symptoms, findings, urinary VMA and HVA levels, primary sites, weights of primary tumor, histology, stages at diagnosis, metastatic sites, and the results of the treatment. Three hundreds twenty eight cases (97%) of them are expected to be cured. And we discussed clinical problems related to mass screening program for neuroblastoma, such as an increase of the incidence of infantile neuroblastomas detected by this program and the spontaneous regression. PMID- 2260869 TI - [Studies on 5-FU concentration and thymidine phosphorylase activity in tissues of patients with colorectal cancer after SF-SP administration]. AB - 5-fluorouracil (5-FU) concentrations in peripheral blood, portal blood, normal and cancer tissues were evaluated in 26 patients with colorectal cancer after SF SP administration (800 mg/day for 10 days). Thymidine phosphorylase activity in cancer tissues was also evaluated. 5-FU concentration in cancer tissues was significantly higher than that in other three specimens, and much higher than 0.05 microgram/g which was reported to be the minimum effective concentration. 5 FU concentration in portal blood was lower than MEC (0.05 microgram/ml). As for the relationship with the pathological features of cancer, the protruding lesions showed a higher 5-FU concentration than the ulcerative ones, and the lesions invaded only to submucosa or proper muscle showed a higher concentration than others. 5-FU concentration ratio in cancer tissues per in peripheral blood (T/B ratio) was related to thymidine phosphorylase activity. The higher was the thymidine phosphorylase activity, the greater T/B ratio. The results suggest that the tumor with higher thymidine phosphorylase activity might have a more pronounced anticancer efficacy of 5-FU. PMID- 2260870 TI - [Mechanism of antitumor effect of a benzoylphenylurea derivative, HO-221]. AB - HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We previously reported HO-221 showed significant antitumor activities against various experimental tumor models, and was especially effective against the solid tumor. In this report we studied the mechanism of action of the compound. The inhibitory activity of HO-221 and 6 kinds of antitumor agents on DNA polymerase alpha was examined in vitro. HO-221 inhibited DNA polymerase alpha activity strongly. From the comparison with IC50 values of individual agents, the inhibitory activity of HO-221 was almost equivalent to aphidicolin and ara-CTP. By double reciprocal plot analysis, the inhibition of HO-221 was found to be non-competitive with the dCTP unlike that of aphidicolin and ara-CTP. Furthermore, HO-221 showed almost no effect on RNA polymerase activity and the protein synthesis. The effect of HO-221 on cell cycle progression of HL-60 cells was examined by flow cytometry analysis. The compound accumulated cells at S phase at a low concentration. The compound showed accumulation of cells in G1, G1-S and G2 + M phases. At higher concentrations, HO 221 increased the G1 phase of tumor cells, stopping the cell cycle progression. Therefore, G1 and S phase accumulation by HO-221 was considered to be correlated with the inhibition of DNA polymerase alpha dependent DNA synthesis. These results suggest that HO-221 is a novel antitumor agent with different mechanism of action from the known antitumor agents. PMID- 2260871 TI - [Antitumor effect of a benzoylphenylurea derivative HO-221]. AB - HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span. PMID- 2260872 TI - [High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group]. AB - A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation. PMID- 2260873 TI - [A randomized trial of endocrine therapy, chemotherapy, and chemo-endocrine therapy in advanced breast cancer]. AB - A randomized trial of endocrine therapy (adreno-oophorectomy, H), chemotherapy (FAC, C), chemoendocrine therapy (FAC + tamoxifen, H'C, or FAC + adreno oophorectomy, HC) was performed in 114 advanced breast cancer patients from September, 1979 to December, 1983, and 106 were evaluable. The response to H, C, H'C, and HC was shown to be 33% (10/30), 54% (14/26), 59% (17/29), and 76% (16/21), respectively. There was a significantly higher response rate in HC group than H group. Higher but not significantly different response was obtained by H'C as compared with H. There were no significant differences in the overall survival among the treatment arms. However, patients treated with H survived longer (greater than 5 years). These results suggest that higher response obtained by chemotherapy, alone or in combination with endocrine therapy does not seem to contribute to the prolongation of survival of the patients. PMID- 2260874 TI - [The influence of liver and renal functions on the changes in serum methotrexate (MTX) level in high-dose MTX therapy]. AB - Sixty times of high dose methotrexate (MTX) with citrovorum factor rescue (HDMTX CF) therapy were applied for 15 patients with osteosarcoma. The serum level of MTX was measured at every 24 hr. by FPIA (Fluorescence Polarization Immuno Assay) method and blood analysis was performed at the same time. Fourtysix parameters were measured in each HDMTX-CF therapy and examined by multiple parameter statistical analyses by a personal computer. In the results, the number of performed chemotherapy, rescue time, serum GOT and creatinine level at 24 hr. were the most relative factors for the change of serum MTX level. PMID- 2260875 TI - [Effect of PMUE therapy (CDDP, MMC, UFT, etoposide) in terminal gastric cancer]. AB - CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was applied to 60 cases of terminal gastric cancer to examine its effectiveness. PMUE therapy consists of i.v. injection of CDDP 75 mg/body and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. Of 42 cases having estimable lesions, 23 (53.8%) showed high rate of effectiveness (PR). Especially, of 23 cases receiving no previous treatment, 15 (65.2%) benefitted by the therapy (PR) and 9 (69.2%) of 13 non-resected cases, to a wonderful extent. Five non-resected cases showed such a reduction in tumor size as made gastrectomy possible. As for the prognosis, one year-survival rate was 34.3, 49.0 and 16.0% for all 42 cases, 23 effective cases and 19 ineffective cases, respectively, with significant (p less than 0.001) prognostic prolongation for effective cases compared with ineffective ones. Side effects were digestive symptoms (85.7%), epilation (81.0%) and myelopathy (73.8%), which were all transitory and recovered. The present PMUE therapy was regarded as one of the best combined chemotherapies for terminal gastric cancer. PMID- 2260876 TI - [Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. AB - Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL. PMID- 2260877 TI - [A case of bone and lung metastasis of breast cancer successfully treated with radiotherapy, chemotherapy and endocrine therapy]. AB - A 34-year-old female patient with breast cancer metastasizing to bone had a remission after a course of treatment with medroxyprogesterone acetate (MPA) 1,200 mg/day, but again had a metastasis to the lungs. The patient was then instituted on a combination therapy with UFT 400 mg/day, and MPA 1,200 mg/day. As a result, the pulmonary metastasis disappeared, along with the consolidation of the bone involved. PMID- 2260878 TI - [Inhibitory effects of CPT-11 on liver metastases in nude mice injected with human pancreatic tumor cells into their spleens]. PMID- 2260879 TI - [Tumor marker--screening for gynecological cancer; personal experience. Utility of tumor markers in screening of ovarian cancer]. AB - PAP smears and biopsies are very effective in mass screening for uterine cancer. However, in this study, we tried to determine whether tumor markers could be useful for ovarian cancer screening. Eight tumor markers (CA125, TPA, CEA, ALP, amylase, LDH, CRP, IAP) were tested in serum samples from 3,540 women and the values were supplied to a CAMPAS (computer aided multivariate and pattern analysis system). Using this system, we managed to reduce the false positive rate to 0.68% but we couldn't prove the sensitivity of this system, because there were no ovarian cancer cases in this group. At this time, it is important to determine the high risk group of ovarian cancer for reducing the cost of mass screening. Finally, if tumor markers are to become more effective for ovarian cancer screening, it will be necessary to find ones that are more sensitive to ovarian cancer. PMID- 2260880 TI - The ultrastructure of dysplastic naevi: comparison with superficial spreading melanoma and common naevocellular naevi. AB - Eleven dysplastic melanocytic naevi with various degrees of dysplasia, as judged by light microscopy, were studied by transmission electron microscopy, and their intra-epidermal melanocytes compared with those of five superficial spreading melanomas and seven common benign naevocellular naevi. Intra-epidermal melanocytes in dysplastic naevi exhibited signs of cellular atypia, which were most pronounced in the dysplastic naevi with histological high-grade dysplasia. A correlation between the degree of dysplasia at the light microscopic level and the degree of cytological atypia at the ultrastructural level was noted, and melanocytes in dysplastic naevi with a high degree of dysplasia had ultrastructural features similar to the melanocytes in superficial spreading melanomas. Our observations support the concept that dysplastic naevi fill the biological gap between benign naevocellular naevi and malignant melanomas and suggest that at least some of the dysplastic naevi must be regarded as potential precursor lesions of malignant melanoma, particularly those exhibiting a high degree of histological dysplasia. PMID- 2260881 TI - Hereditary palmoplantar keratosis of the Gamborg Nielsen type. Clinical and ultrastructural characteristics of a new type of autosomal recessive palmoplantar keratosis. AB - A new kind of diffuse palmoplantar keratoderma with autosomal recessive inheritance and without associated symptoms was described in Norrbotten, Sweden by Gamborg Nielsen in 1985. Clinically, it ranges between the less severe dominant Unna-Thost type and the more severe recessive Meleda type, as it is milder than the latter. Skin biopsies of five patients from three different families with this new palmoplantar keratoderma, as well as five obligatory heterozygotes from one family, were investigated ultrastructurally in order to characterize this new entity and to differentiate it from the Meleda type. Several features are common to both autosomal recessive palmoplantar keratoses. They show a broadened granular layer, a transit region consisting of cells with a marginal envelope, and considerable hyperkeratosis. Morphologically, this transformation delay is less pronounced in the Gamborg Nielsen type than in the classical Meleda type. As is typical for ridged skin, both types of palmoplantar keratoses possess composite keratohyaline granules. In contrast to the normal appearance of keratohyaline granules in the Meleda type, the Gamborg Nielsen type also shows qualitative deviations of keratohyaline granules with different degrees of spongiosity and electron density and sometimes with a granular border. It seems that abnormal keratohyaline proteins are synthesized that behave differently. The sudden transformation of a granular into a horny cell is physiologically regulated by different enzymes. A delay in this process may be caused by a mutation that reduces or alters the enzymes concerned. We assume the palmoplantar keratoderma of the Gamborg Nielsen type to be a variant of the heterogeneous group of the Meleda type of palmoplantar keratoderma with autosomal recessive inheritance. PMID- 2260882 TI - Detection of migration inhibitory factor (MIF) by a monoclonal antibody in the microvasculature of inflamed skin. AB - Macrophage migration inhibitory factor (MIF) is known as a mediator of cellular immunity with specific effects on the differentiation of mononuclear phagocytes. There is little information on the production of MIF in vivo and its role in the pathophysiology of inflammation. We studied the distribution of MIF in various tissues with a monoclonal antibody against human MIF (1C5/B) using the indirect immunoperoxidase method. Here, we investigate the expression of MIF on endothelial cells of dermal vessels. Our results show that dermal vessels may constitutively express MIF and can be strongly activated to express MIF in acute inflammations such as eczema and psoriasis in contrast to the chronically infiltrated skin from patients with pseudolymphomas and sarcoidosis. In these cases a possibly MIF defective state of vessels and a restriction of positive vessels to distinct anatomical sites of the inflamed skin was detected. The significance of the described association of MIF with vascular endothelium is still a matter of speculation. MIF expression on endothelium may provide an important differentiogenic signal for mononuclear phagocytes on their way to the tissue site. PMID- 2260883 TI - Electron microscopic study of cultured cells from the murine hair tissues: cell growth and differentiation. AB - The cultured hair cells from 4-day-old C3H mice were studied by electron microscopy. The hair roots isolated from the skin by collagenase digestion were dispersed into a cell suspension by treatment with a mixture of trypsin and ethylenediaminetetraacetate. The cells were cultured in MCDB-153 (a medium containing seven growth factors) for 1, 3, 6 or 13 days. The number of cultured cells on day 3 was twice that on day 1, and stayed at the same level until day 13. By electron microscopy, some of the cells cultured for 1 day were seen to be undifferentiated and others already showed differentiation into various hair structures. Such differentiated cells disappeared on day 3 and most of the cells cultured for 3 days were undifferentiated. Cell cultured for 6 days were differentiated showing inner root sheath cell, hair cortical cell and medulla cell structures. The characteristics of these cultured cells corresponded well to those of in vivo cells of the hair tissues from the back skin of 7-day-old C3H mice. On day 13 degeneration occurred in the cultured cells. In none of these cultures were mesenchymal cells, such as fibroblasts, found. The present electron microscopic study reveals that immature cells obtained from mouse hair tissues proliferate in vitro and differentiate into several subpopulations corresponding to those of in vivo cell layers of hair tissues. The present culture technique may be useful for studies of hair cell growth and differentiation. PMID- 2260884 TI - Effects of topical cyclosporin A on guinea-pig toxic contact dermatitis. AB - It is known that the topical application of cyclosporin A (CsA) has a significant suppressive effect on allergic contact dermatitis. In this study, we investigated the effect of topical CsA on toxic (non-allergic) contact dermatitis. Topical CsA significantly suppressed the toxic contact reaction to croton oil. This suppressive effect was short-lived and reversible. Significant inhibition of the reaction to croton oil persisted for 3 days after stopping the CsA. The toxic reaction was blocked when CsA was applied within 6 h of the croton oil application, but when application of CsA was delayed until 12 h after the oil application there was no significant suppressive effect. Topical administration of CsA could become a valuable tool for treating toxic and allergic contact dermatitis without producing the adverse reactions caused by systemic therapy. PMID- 2260885 TI - Detection of pemphigus vulgaris antigen on COLO and SCaBER tumor cell lines by the immunoblot technique. PMID- 2260886 TI - Dilemmas and directions for psychiatric nursing in the 1990s. AB - Problems with the recruitment of nurses to the specialty area of psychiatric nursing have stimulated much debate and discussion in the field. This article explores dimensions of psychiatric nursing education, science, and practice and their impact on the future of this specialty area of nursing. It proposes that the present task is to define more precisely the continuum of psychiatric mental health nursing both to differentiate between psychosocial (mental health) and psychiatric (mental illness) components of the role and balance the priority that psychiatric nurses give to each in educational curricula, research agendas, and practice settings. PMID- 2260887 TI - The pragmatics of culture: the rhetoric of difference in psychiatric nursing. AB - Culture becomes an issue in the treatment of psychiatric patients from diverse cultural backgrounds. Inpatient psychiatry at an urban, general hospital in San Francisco, California, has developed specialized treatment programs for Hispanic, black, and Asian-Pacific patients. These patients are recognized as culturally distinct; their cultural situations must be addressed by a program of culturally sensitive nursing care. The implementation of such a program has not generally led to serious cultural analysis on the part of nurses and other caregivers but rather, to a rhetorical and strategic use of the concept of culture and a stereotyping of traits, styles, and beliefs. This article critically examines this rhetoric of cultural difference as an aspect of the rhetoric of normalization practiced in this setting. PMID- 2260888 TI - Self-care actions of chronic schizophrenics associated with meeting solitude and social interaction requisites. AB - Solitude becomes a way of life and social interaction a scarce commodity for many chronic schizophrenics who are in institutional settings. This article describes the self-care actions associated with meeting solitude and social interaction requisites as reported by 10 institutionalized chronic schizophrenics. Eighteen solitude self-care actions and 10 social interaction self-care actions emerged from the interview data. The solitude self-care actions clustered around two distinct categories: distancing and organizing. The social interaction self-care actions clustered around one category, managing situations. The implications of this study extend to anyone who is in the position of providing care and support to an individual diagnosed as a chronic schizophrenic. Additional research is suggested to increase the generalizability of the findings of this study and to isolate conditions related to Orem's (1985) sets of actions for maintenance of a balance between solitude and social interaction. PMID- 2260889 TI - The water-intoxicated patient. AB - In a long-term psychiatric setting, self-induced water intoxication may be a life threatening situation. At first glance, the symptoms or behaviors of self-induced water intoxication are similar to schizophrenia, i.e., inappropriate behavior, delusions, hallucinations, confusion, and disorientation. In some cases, the symptoms of water intoxication mimic schizophrenia and thus, are disguised as a part of the psychoses. Affected individuals develop polydipsia, which is accompanied by overhydration and dilutional hyponatremia. If untreated, the symptoms may progress from mild confusion to acute delirium, seizures, coma, or death (Ripley, Millson, & Koczapski, 1989). Under normal circumstances there is a delicate balance of water requirement and water intake. If the balance of water is altered, electrolyte imbalance can occur. The recognition of water intoxication or self-induced water intoxication and psychosis among chronic, institutionalized patients may prevent their death or the development of neurological damage (Arieff, 1985). Because self-induced water intoxication often goes unrecognized in its early stages and may have irreversible or fatal complications, early detection is crucial. This article will discuss the etiology, nursing assessment, and interventions associated with patients suffering from self-induced water intoxication. PMID- 2260890 TI - Munchausen's syndrome by proxy as a form of child abuse. AB - Munchausen's syndrome by proxy (MSBP) is an emotional disorder in which the parent, almost always the mother, induces or fabricates illness in her child in order to gain medical attention. Although numerous case studies exist in pediatric and medical literature, most nurses are unaware of the warning signs of this disorder. Psychiatric consultation liaison nurses are in an ideal position to identify and intervene in MSBP situations and can also support the pediatric nursing staff through feelings of denial, shock, and guilt as they recognize the syndrome and its danger to the child. PMID- 2260891 TI - Men with cardiovascular disease and their spouses: coping, health, and marital adjustment. AB - This study examined the coping methods, health perceptions, and marital adjustment of 37 middle-aged men with chronic cardiovascular disease and their spouses. Despite variation in disease types and the absence of disease among the spouses, the couples were similar in their coping responses. Both partners used more emotionally focused strategies than problem-focused strategies to cope with chronic illness. Subjective health perceptions were more useful than objective indices for predicting coping. Preillness and current marital adjustment were satisfactory for both partners. The major implications for nursing practice are in the area of assessment, and suggested interventions are discussed. PMID- 2260893 TI - Differentiation of hopelessness, helplessness, and powerlessness using Erik Erikson's "Roots of virtue". AB - Hopelessness, helplessness, and powerlessness have been identified as phenomena of concern to psychiatric nursing practice by an American Nurses' Association (ANA) task force. These concepts, however, have not been clearly distinguished from each other. The resulting lack of clarity decreases the usefulness of nursing diagnoses in directing strategies for intervention. The purpose of this article is to differentiate the phenomena of hopelessness, helplessness, and powerlessness using Erik Erikson's "Roots of virtue" as a conceptual framework. The relationship between the frustration of early childhood tasks and later adult response patterns is discussed. Clinical examples illustrate that knowledge of childhood issues guides the formulation of therapeutic goals and interventions to address the experience of hopelessness, helplessness, and powerlessness. PMID- 2260892 TI - Pregnancy resolution decisions in juvenile detention. AB - A group of detained pregnant adolescents and expectant teenage fathers served as participants in a qualitative research project designed to describe how adolescents residing in a large metropolitan area juvenile detention facility make health- and pregnancy-related decisions. During the course of the study and clinical work with this population, it was found that although troubled and troublesome, these teenagers do not present as bleak and depressing a picture as might appear on the surface. Three primary themes emerged from the study findings: responsibility, reputation, and respect. These themes were bound to the important relationships in the teenagers' lives. The participants also presented some surprising strengths and resolutions for the future that psychiatric and liaison nurses working in the setting can use in program planning and clinical interventions. PMID- 2260894 TI - Detection of malaria endemicity in community villages in North Sumatra, Indonesia by enzyme linked immunosorbent assay. AB - An enzyme linked immunosorbent assay for malaria was used in North Sumatra, Indonesia as an epidemiological survey tool. The seroepidemiological investigation was concentrated on junior high schools. Serum samples obtained were classified according to the villages of origin of the students. The mean of ELISA values of each village group was compared with the parasite rate in primary schools in their native villages. A good correlation was observed between them (r = 0.96). The present results indicate that a survey of malaria in junior high schools by ELISA could give useful information on malaria prevalence in several peripheral villages. Province-wide information on malaria prevalence could easily be obtained by malaria-ELISA in junior high schools in tropical rural area. PMID- 2260895 TI - Malaria in the Amazon. Prevalence of Plasmodium falciparum antibodies in Amerindians inhabiting the Venezuelan Amazon. AB - The acquisition of antibodies to Plasmodium falciparum in various age groups was studied in 511 Amerindians inhabiting the north of the Venezuelan Amazon. The overall prevalence by ELISA was 91.2% and antibodies were acquired early in life. Seropositivity was 69.6% in the group aged two to five years and reached 86% at 10 years of age; 96.9% of the adults aged 31-40 years exhibited high ELISA values to P. falciparum. The high prevalence of malaria antibodies among Amazonians, from early on in life, reflects the high level of malaria transmission in that part of the world. PMID- 2260896 TI - Acetylated low-density lipoprotein as a vehicle for antiinfectious drugs: preparation and antileishmanial activity of Ac-LDL containing ketoconazole oleate. AB - Previous studies have demonstrated that mouse peritoneal macrophages take up low density lipoproteins (LDL) which have been chemically modified by the acetylation of lysine residues (Ac-LDL). This uptake is mediated through a specific receptor known as the scavenger receptor. Ac-LDL therefore appear to have excellent potential for antiinfectious drug targeting. We have developed a new method to incorporate ketoconazole-oleate, a lipophilic derivative of ketoconazole, into Ac LDL. The method involves solubilization of LDL in the presence of Na deoxycholate, the addition of a micellar solution of the drug to be incorporated, and the subsequent removal of the detergent leading to the formation of reconstituted LDL (referred to as LDL-KOL). The LDL-KOL contain 200 drug molecules per LDL particle and compete for the binding of native 125I-LDL on human skin fibroblast monolayers. Furthermore, reconstituted LDL-KOL are indistinguishable from native LDL with regard to lipid composition and electrophoretic mobility. LDL-KOL, when acetylated, are recognized by the scavenger receptor. Acetylated LDL-KOL show antileishmanial activity when tested on infected macrophages. The activity appears to be mediated through the scavenger-cell pathway, as LDL-KOL are inactive under the same conditions. Moreover, acetylated LDL-KOL are selectively accumulated within infected macrophages rather than in normal cells. This may be of value in the treatment of intracellular infections. PMID- 2260897 TI - The intestinal faunas of man and mountain gorillas in a shared habitat. AB - The primate fauna of the Impenetrable (Bwindi) Forest in southwest Uganda includes both man and the mountain gorilla Gorilla gorilla beringei. The intestinal parasite faunas of these two species were described by examining faecal samples. Of 16 parasites in the combined fauna only one, Strongyloides fuelleborni, was shared by both host species. PMID- 2260898 TI - Interference of Echinoparyphium elegans with the host-parasite system Bulinus truncatus-Schistosoma bovis in natural conditions. AB - Histological observations of Bulinus truncatus naturally infected by both Schistosoma bovis and Echinoparyphium elegans in Sardinia (Italy) have shown that E. elegans is pathogenic to the mollusc and dominant to the schistosome. The larval stages, rediae and metacercariae, acted as compressors. Rediae, mainly the young and very motile ones, also behaved as predators. The organs of the mollusc were variably affected; the ovotestis totally disappeared. The larval development of the schistosome was disturbed; cercariogenesis was strongly inhibited and gave way to high sporocystogenesis. The intensity of this interference depended on the density of echinostome larvae present. PMID- 2260899 TI - Delta infection in chronic HBs Ag carriers in Tunisia: high prevalence in chronic asymptomatic HBs Ag carriers and in HBs Ag positive cirrhosis. AB - The presence of hepatitis B virus DNA, delta antigen and anti-delta antibodies was examined in 159 Tunisian chronic HBs Ag carriers: 45 were asymptomatic and 114 suffered from cirrhosis. Serum hepatitis B virus DNA was detected in two (4.5%) asymptomatic HBs Ag carriers and in 11 (10%) HBs Ag positive cirrhosis patients. The prevalence of HDV infection determined by the presence of anti delta was relatively high in asymptomatic HBs Ag carriers (33%) and in HBs Ag positive cirrhosis patients (21%). Active ongoing HDV infection, detected by serum HD Ag and anti-delta IgM, was shown in five patients with cirrhosis and active hepatitis B virus replication. We conclude that hepatitis delta virus may be endemic in Tunisia and does not always inhibit hepatitis B virus replication. PMID- 2260900 TI - Hydatid disease in the Turkana District of Kenya, VII: analysis of the infection pressure between definitive and intermediate hosts of Echinococcus granulosus, 1979-1988. AB - The rate of acquisition of Echinococcus granulosus and Taenia hydatigena was examined in dogs treated with praziquantel in northwestern Turkana District of Kenya. An attempt was also made to assess the effect of drought on the prevalence of E. granulosus. The infection pressure to dogs with the cestodes was shown to be high, and the prevalence returned to pretreatment levels within six months. The unreliability of arecoline purging in prevalence studies of dog cestodes is shown by mathematical contrast to the results of autopsy. Arecoline purge may underestimate the real prevalence by 10-fold. Dosing intervals in hydatid control programmes utilizing mass dog-purging to estimate re-infection rates should therefore take this factor into consideration. It is proposed that a mass dog dosing schedule in Turkana, using praziquantel, should take into consideration the short prepatent period of E. granulosus, the financial constraints, and the slaughter practices in the area. During the prolonged droughts which occur approximately every 10 years, the programme will be adjusted accordingly to cater for the initial increase in infection intensity to dogs. PMID- 2260901 TI - The onchocerciasis focus at Kinsuka/Kinshasa (Republic of Zaire) in 1985. I. Entomological aspect. AB - The entomological aspect of the onchocerciasis focus at Kinsuka/Kinshasa has not been studied since vector control was carried out in 1948. As in 1940, larvae of Simulium damnosum s.l. are located in the arm of the Zaire River flowing between Mimosa Island and the Zairian bank. They are, however, scarce. Cytotaxonomic studies showed that the S. squamosum group was the only member of the S. damnosum complex present in the region of Kinshasa. Physico-chemical analysis of the water at breeding sites determined that S. squamosum larvae develop in neutral or acid water with a conductivity of less than 50 micronhos cm-1 and a low concentration of dissolved salts. Longitudinal study showed that the 'annual biting rate' (ABR) and the 'annual transmission potential' (ATP) fluctuate from 2406-5999 bites man 1 year-1 and from 120-236 infective larvae man-1 year-1 respectively. The low transmission rate at Kinsuka is mainly due to the low level of the biting population occurring during the main river rising. The increase in Kinsuka's population has reinforced this situation by 'diluting' the parasite in the human reservoir. PMID- 2260902 TI - The susceptibility of five laboratory colonies of mosquitoes to the human nematode Wuchereria bancrofti (Cobbold). AB - Laboratory colonies of Anopheles gambiae, An. arabiensis, An. merus, An. quadriannulatus and Aedes aegypti formosus were artificially fed on blood containing microfilariae of Wuchereria bancrofti. The anopheline colonies all supported parasite development to the infective stage, with An. quadriannulatus being the most heavily infected. The parasite did not develop at all in the Ae. aegypti formosus colony. PMID- 2260903 TI - Effect of diethylcarbamazine on adult Loa in monkeys. AB - The effect of diethylcarbamazine citrate (DEC) treatment (43-150 mg kg-1 daily for 12-21 days) on adult Loa worms in five drills (Mandrillus leucophaeus) is described. In individual monkeys, between one-third and all of the adult worms survived the treatment, and most of the surviving females were still producing live microfilariae. These experiments provide direct evidence which may explain the common clinical experience that single courses of DEC do not always succeed in eliminating the signs and symptoms of loiasis in humans. Further work on the chemotherapy of loiasis in monkeys, using DEC and other filaricides, might improve the treatment of this disease. PMID- 2260904 TI - The effect of histamine on the immune response of hamsters to infection with Ancylostoma ceylanicum. AB - The role of histamine in modulating the immune response of hamsters infected with Ancylostoma ceylanicum (hookworm) was investigated. Histamine administration (20 mg base/hamster x 6 ip) made the immune hamsters susceptible to challenge infection, and on assay the humoral as well as the cell-mediated responses were found to be suppressed. An adverse effect of histamine was observed on lymphocytes but the macrophage function remained unaltered, since the latter lack histamine receptors. These findings provide definite evidence that histamine suppresses specific immune responses, and that contrary to earlier reports this neurotransmitter does not play a direct role in the 'self-cure' phenomenon. PMID- 2260905 TI - Predation and control of laboratory populations of the snail Biomphalaria glabrata by the freshwater prawn Macrobrachium rosenbergii. AB - Laboratory experiments were conducted on predation by the giant freshwater prawn, Macrobrachium rosenbergii, on Biomphalaria glabrata, a snail intermediate host of human schistosomiasis. Prawns greater than 22 mm carapace length could consume snails of any size. Smaller prawns exhibited a size-specific upper limit on the size of snail they could kill. Below the maximum size of prey consumed, little selectivity for prey size was demonstrated. All prawns heavier than 2.5 g killed the largest size of snail offered (16 mm diameter). Consumption, in terms of the numbers of snails killed, and the snails' wet weight and percentage of prawn body weight eaten per day, increased with prawn size. Large prawns consumed snails at a high rate (39% of body weight per day). Population experiments demonstrated that a prawn of 25 mm carapace length could eliminate 95% of a population of 80 snails in a 20-1 aquarium within 20 days and all snails by day 40. A prawn of 15 mm carapace length could not eliminate all snails. Large snails (24% of the initial population) had some protection from predation because of their size. Although the snails bred continuously, no snails were able to recruit to these populations in the presence of small prawns. In contrast, snail populations in control aquaria without prawns expanded to a mean of 919 snails by the end of the experiment (day 70). Since M. rosenbergii are voracious predators on B. glabrata, exhibit considerable habitat overlap with the snail prey, and are likely to treat snails as highly preferred food, further experimentation on these prawns in the context of biological control of schistosomiasis is warranted. The ready availability of prawns through established prawn hatcheries and the synergistic use of these prawns in aquaculture may ensure the reliability of stocking procedures and meet the standards of availability and cost-effectiveness required of a biological control agent. Polyculture of Macrobrachium with fin fish (Tilapia) indicates that these prawns may be a particularly useful control agent in aquacultural environments. PMID- 2260906 TI - Cytoadherence of Plasmodium falciparum-infected alpha-thalassaemic red cells. PMID- 2260907 TI - The subspecies of Echinococcus granulosus in Great Britain. PMID- 2260908 TI - A rapid method for the determination of worm load in cases of Taenia infection in the field. PMID- 2260909 TI - A record of Glossina medicorum Austen (Diptera: Glossinidae) from Uganda. PMID- 2260910 TI - Premenstrual syndrome as a criminal defense. AB - Premenstrual syndrome may be effective as an affirmative defense to a criminal charge if the defendant can show that (i) she was suffering from premenstrual syndrome at the time the crime was committed; and (ii) because of her condition, either that the criminal act was an involuntary act or that at the time of the criminal act she did not possess the mental state required by law for the commission of a crime. Premenstrual syndrome has been successfully pleaded as a criminal defense in Great Britain but has not been tested in American criminal courts. It may now be possible, however, because of the increase of behavioral, psychological, and physiological studies precisely characterizing premenstrual syndrome and elucidating the necessary criteria for its accurate diagnosis, for the appropriate defendant to assert this defense in an American court. This paper discusses (i) the use of recent scientific data to demonstrate the existence of premenstrual syndrome; (ii) the use of standardized psychological tests or physiological assays to demonstrate that the defendant suffers from premenstrual syndrome; and, (iii) the legal choices to be made and evidentiary hurdles that must be overcome in presenting a premenstrual syndrome defense. PMID- 2260911 TI - Affective and personality characteristics of MMPI profile subgroups of incarcerated rapists. AB - Psychometric studies attempting to understand adult rapists have primarily used the MMPI and have been of limited use. Also, psychodynamic theories have failed to provide objective criteria for classification. The present study attempted to integrate these two approaches. Using multivariate clustering procedures, five MMPI profile subgroups were identified. Subgroups replicated those identified in earlier studies. Subgroups were also differentiated along several sexual, affective, and personality measures independent of the MMPI. Results are integrated with psychodynamic theories of rape and implications of the findings and the utility of a classification system for rapists are discussed. PMID- 2260912 TI - Sexual fantasies of heterosexual and homosexual men. AB - Heterosexual men and homosexual men rated how arousing different sexual fantasies were and how often they had used these fantasies over the previous year. Within each group, sensual and genital same-orientation fantasies were more arousing than either public-sex or dominance-submissive fantasies, which in turn were more arousing than aggressive-sex fantasies. For both heterosexual and homosexual men the extent to which a fantasy was arousing correlated with the person's experience of the activity depicted in the fantasy. The frequency of use of a fantasy correlated positively with its arousal level but not always substantially so. The results are discussed in the context of the mediating role of fantasy in human sexual arousal. PMID- 2260913 TI - Enhancement of fantasy-induced sexual arousal in men through training in sexual imagery. AB - Men who in earlier experiments in the same laboratory had been unable to enhance penile tumescence to any substantial degree by engaging in erotic fantasy were given two sessions of either sexual imagery training or general imagery training. Participants in the sexual imagery training program subsequently demonstrated increased physiological and subjective sexual arousal during unstructured as well as structured sexual fantasy. The gains were undiminished at follow-up, 1 month after the end of training. In contrast, general imagery training did not enhance fantasy-induced sexual arousal. Both training programs improved vividness of imagery, as assessed by the Betts QMI Scale, but only sexual imagery training led subjects to report that they were able to form sexual images with higher clarity when engaging in fantasy. Sexual arousal was thus enhanced through context specific imagery training, a strategy commonly used in the clinical practice of sex therapy. PMID- 2260914 TI - Clinical patterns among male transsexual candidates with erotic interest in males. AB - Male-to-female transsexuals who reported an erotic interest in males showed different patterns of sexual activity. Sexual history was used to categorize a transsexual sample into three groups: 44% abstained from sexual activity (Inactive group), 19% were sexually active but avoided using their penis in sexual activity (Avoidant group), and 37% were sexually active and derived pleasure from their penis (Pleasure group). The groups were compared for differences in gender identification, developmental patterns, and personality. Transsexuals in the Avoidant group showed patterns of traits and experiences that generally conformed to characteristics of the nuclear transsexual. They were dissimilar from the other two groups on measures of feminine functioning, heterosexual history, and fetishism. Transsexuals who interact with males in ways that are viewed as more classically homosexual shared more in common with the transsexual group which abstained from sexual activity with males. Both groups displayed more masculinity in development and more evidence of emotional disturbance. The implications of these findings for diagnosis and treatment are discussed. PMID- 2260915 TI - Effect of estrogens on prolactin secretion in transsexual subjects. AB - The effect of estrogens on the secretion of prolactin in 8 different groups of transsexual subjects was studied. Two different types of estrogens, estradiol or its conjugate and ethinyl estradiol, were used. Different doses and durations of exposure were employed. Plasma levels of prolactin and SHBG after estrogen exposure were compared with corresponding levels before treatment. Results showed that for estrogens to exert an enhancing effect on the secretion of prolactin, three factors needed to be considered: (i) the absolute concentration of estrogen, (ii) the duration of exposure, and (iii) whether levels of SHBG are sufficiently altered to change the concentration of free estrogen. It appears that there exist both time and dose thresholds for effective enhancement of prolactin secretion by estrogen. Estradiol and its conjugate are more likely to induce hyperprolactinemia than ethinyl estradiol. The reduced effect of the latter is probably related to its ability to induce large and rapid increases in SHBG binding which probably results in unaltered free estrogen concentration. In the light of this study, treatment of male transsexuals with high doses of estradiol in its conjugate forms must be viewed with caution. PMID- 2260916 TI - AIDS-phobia and political reaction in California: student versus public responses to reactive political initiatives. AB - A "social reactivist" study was conducted of the responses of 563 students enrolled in a Southern California university compared with those of a random sample of 1002 Californians telephone-polled by the California Poll. The study focused on AIDS-phobia, the fear of getting AIDS or the AIDS virus, HIV, from casual contact. In both samples, AIDS-phobia correlated well with reactive political sentiment. Students who were AIDS-phobic were expected to vote in favor of proquarantine initiatives (Proposition 64 in 1986 and Proposition 69 in June 1988). California Poll respondents who were AIDS-phobic, likewise, were expected to vote in favor of Proposition 102 (November 1988) which required reporting HIV positive patients to local health officers. In the student samples, however, AIDS phobia was found by factor analysis to have two subsets: AIDS-phobia-Wet and AIDS phobia-Dry. These did not appear in the California Poll results. In the 1988 student sample, AIDS-phobia-Wet was significant in explaining proquarantine sentiment, while AIDS-phobia-Dry proved significant in explaining sexual activity. The converse was not true. AIDS-phobia is a major characteristic of the social audience to AIDS as a disease and may prove decisive in the evolution of the disease. Support for the victim (or lack of it) may influence the course of the disease and even public funding to fight the disease. AIDS-phobia may also blind heterosexuals to their own vulnerability, thus making them vulnerable to the disease. PMID- 2260917 TI - [Fat clogging, fat cell count and fat cell size in swine in relation to age and feeding intensity]. AB - Growth dependent changes of fat gain, the number of fat cells in the cutlet muscle and the size of the fat cells in the bacon of the back were studied in dependence on feeding intensity with a total of 145 male castrates of the genotype (L X E) XSF. Between their 5th and 32nd weeks of life the animals were butchered at intervals of 3 weeks and the parameters were determined. The gain of fat and the intramuscular fat content were highest in the high-level variant (daily weight gain 720 g) and lowest in the low-level variant (daily weight gain 530 g). The diameter of the fat cells in the middle layer of the bacon of the back increased up to an age of 26 weeks and then remained constant. Differences between the feeding groups were registered; the animals of the high-level group had the biggest fat cells from the 14th week onwards. A nutrition-caused difference between the number of fat cells per mm2 of the cutlet muscle could not be found. The calculated total number of fat cells in the cutlet muscle increased due to growth up to an age of 26 weeks. The results provided basic knowledge of fat gain and influences on it in pigs and they indicate possibilities of making statements on fat retention determining the microstructure of the fat tissue of the living animal by means of biopsy. PMID- 2260918 TI - Protein digestion in pigs measured in vitro. AB - In vitro determination of protein digestibility by treating feedstuffs with pepsin-HCl respectively with pepsin and trypsin yields results that differ considerably from the ileal protein digestibility figures. Comparable results for N and lysine are received when the largest polypeptides in the solution obtained after peptic and tryptic treatment are precipitated with copper hydroxide. PMID- 2260919 TI - The apparent ileal and faecal digestibilities of amino acids and carbohydrates of rye, barley and triticum grains in pigs. AB - Six pigs of initial weight 40 +/- 1.7 kg with a T-piece cannula fitted at the terminal ileum were given diets composed of 96.3% of rye, barley or triticum grains ground to pass the 2.6 mm mesh, 3.3% mineral and vitamin mixture and 0.4% Cr2O3. Each diet was given to all pigs in a Latin square design, and faeces and ileal digesta were collected on 7, 8, 9 and 10, 11 and 12 day of feeding each diet, respectively. The grains varied widely in the content of pentosans, polyuroids, beta-glucan and monosaccharides. The antitrypsin activities were 0.84, 2.73 and 1.62 TUI/g in barley, rye and triticum, respectively. Ileal and faecal apparent digestibilities of nitrogen and amino acids were higher (P less than or equal to 0.01) in Triticum than in barley and rye. The digestibility of carbohydrates (pentosans, beta-glucan, polyuroids and non-structural carbohydrates) were lower in pigs fed a rye diet than of those fed a Triticum diet. The results are discussed with respect of the role to non starch polysaccharides, especially pentosans in digestibility of nitrogen and energy in animals receiving a rye diet. PMID- 2260920 TI - Growth and carcass composition of female turkeys implanted with anabolic agents and fed high-protein and low-protein diets. AB - This laboratory investigated the anabolic effect of the synthetic steroid trienbolone acetate (TA) and found it effective in male and female meat turkeys without any apparent gross abnormalities (Poultry Sci., 61: 1386, 1982). The present study was undertaken to characterize the response of female turkeys, fed equicaloric diets varying in dietary protein density to anabolic agents implanted at 13 wks. TA and zeranol (Z) were tested singly and in combination (TAZ). Body weight gain and feed conversion at 16 wks of age were improved (P less than 0.01) with TA and TAZ. The response to TA was enhanced as dietary protein density increased. Carcass fat, protein, ash, energy, potassium, and calcium were not altered by implant treatment. A trend existed toward increased carcass fat with zeranol implantation. Carcass moisture (P less than 0.01) and sodium (P less than 0.05) were increased in the TA treatment. Blood plasma electrolytes were not affected by implant treatments but plasma calcium was decreased (P less than 0.05) by TAZ. No synergism was noted between TA and Z with respect to growth, feed conversion, carcass composition, plasma electrolytes with the exception of plasma calcium. No interaction was observed between dietary protein density and implant treatment. Performance variables increased and carcass fat decreased with increasing dietary protein density. These results confirm our earlier finding with respect to TA and provide additional evidence that dietary protein density influences the response of meat turkeys to TA. The data show that zeranol lacks an anabolic effect in turkeys. PMID- 2260921 TI - [The ruminal nitrogen metabolism in calves and sheep. 2. Studies in wethers]. AB - Energetically differing rations which received ca. 45% of their crude protein from a supplement of soybean oil meal or urea were tested in a model experiment with adult wethers fitted with duodenal re-entrant cannulae or rumen cannulae resp. The N-equivalent exchange of soybean oil meal by urea in wethers resulted in a distinct increase of the NH3-N content of the rumen fluid, an increase of irreversible N losses and thus a worsening of the utilization of the available N for bacterial N-efficiency. A significant influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of the duodenal NAN could not be detected. The increase of the energy level of the rations did not have a significant influence on the parameters of the ruminal N metabolism in the wethers. The studies with calves and adult wethers showed that a transposition of the parameters of ruminal N metabolism obtained to calves is not possible under the conditions given. PMID- 2260922 TI - Odontoglossum ringspot virus coat protein: sequence and antigenic comparisons with other tobamoviruses. AB - Comparative immunochemical analysis of different tobamoviruses indicated that the previously reported coat protein sequence of Odontoglossum ringspot virus was likely erroneous. This sequence has been determined again by direct sequencing of the genomic RNA and was found to differ from the previously proposed sequence in 31 of the 157 amino acid residues. The extent of antigenic cross-reactivity between ORSV protein and other tobamovirus proteins was measured by ELISA and found to correlate satisfactorily with the degree of sequence homology. PMID- 2260924 TI - NCI-H292 as an alternative cell line for the isolation and propagation of the human paramyxoviruses. AB - Primary rhesus monkey kidney (MK) cells have long been the cells of choice for isolation and propagation of the human paramyxoviruses (parainfluenza 1, 2, 3, 4A, 4B, and mumps). However, problems with the supply and cost of MK cells and the presence of endogenous viruses, including herpes B virus and SV-5, necessitated a search for an alternative cell line. Continuous cell cultures of human origin (L132, A-549, HuT-292, HEK, G-293, G-401, A-498, A-704, CAKI-1, RD) and simian origin (LLC-MK2, BSC-1, MA-104, Vero) were evaluated for their capacity to support the growth of the human paramyxoviruses, as followed by cytopathic effect, hemadsorption, hemagglutination, and EIA. NCI-H292 (HuT-292) human lung mucoepidermoid carcinoma cells (ATCC # CRL-1848) proved to be the most sensitive line for cultivating all serotypes and strains of the paramyxoviruses. These cells were also shown to be a suitable substitute for MK in primary isolation of paramyxoviruses from clinical specimens. RPMI-1640 with 1.5 micrograms/ml trypsin was the preferred maintenance medium; alternatively, Eagle's MEM supplemented with 1.5 micrograms/ml trypsin and 0.1% ITS was satisfactory. NCI-H292 cells are a continuous line with excellent growth characteristics, although the genetic polyploidy of the cells may limit the number of passages of usable cells. PMID- 2260925 TI - [Recent progress in the treatment and diagnosis of allergic conjunctivitis]. PMID- 2260923 TI - Expression of the structural proteins of dengue 2 virus and yellow fever virus by recombinant vaccinia viruses. AB - Vaccinia virus recombinants were constructed which contained cDNA sequences encoding the structural region of dengue 2 virus (PR159/S1 strain) or yellow fever virus (17D strain). The flavivirus cDNA sequences were expressed under the control of the vaccinia 7.5k early/late promotor. Cultured cells infected with these recombinants expressed immunologically reactive flavivirus structural proteins, precursor prM and E. These proteins appeared to be cleaved and glycosylated properly since they comigrated with the authentic proteins from dengue 2 virus- and yellow fever virus-infected cells. Mice immunized with the dengue/vaccinia recombinant showed a dengue-specific immune response that included low levels of neutralizing antibodies. Immunization of mice with the yellow fever/vaccinia recombinant was less effective at inducing an immune response to yellow fever virus and in only some of the mice were low titers of neutralizing antibodies produced. PMID- 2260926 TI - [A novel liquid-phase enzyme immunoassay AlaSTAT for IgE antibody determination]. AB - To determine whether a novel liquid-phase enzyme immunoassay AlaSTAT for allergen specific IgE antibody determination can be used to measure the absolute amounts of serum IgE antibodies, we examined the amounts of anti-house dust (HD) and anti mite IgE antibodies in sera of 32 HD-sensitized allergic asthmatics and 14 normal subjects by this immunoassay. The amounts of anti-mite IgE antibody in serum measured by this immunoassay were found to be consistent with those assessed by the difference in serum total IgE proteins before and after the absorption with mite allergen (the value determined by this immunoassay was 113% of the latter one, n = 4). Neither nonspecific IgE protein (50 to 10000 IU/ml) nor the heat inactivated blocking serum affected the measurement of allergen-specific IgE antibody by the liquid-phase immunoassay. There were strong correlations between the values of anti-HD and anti-mite IgE antibodies by RAST and those by AlaSTAT (r = 0.90, p less than 0.001 and r = 0.86, p less than 0.001, n = 46, respectively). Our results indicate that the commercially available liquid-phase allergen-specific IgE enzyme immunoassay can be used to measure the absolute amounts of serum IgE antibodies without interference of nonspecific IgE protein or IgG blocking antibody. PMID- 2260927 TI - [Study on the frequency and clinical significance of positive RAST for mould allergen in asthmatic patients]. AB - Recently, moulds are considered to be important allergens for bronchial asthma. To confirm this fact, 76 asthmatic patients (mean age 12.5, range 6-17 years) admitted to National Chubu Hospital were investigated for 16 different mould allergens by Pharmacia RAST RIA to measure specific-IgE for moulds. The results were as follows. 1) The frequency of positive RASTs (score greater than or equal to 2) varied from 4% to 21% depending on the allergen. Because 21 patients were RAST positive to one or more allergens, ultimately 26 patients (34%) appeared to be RAST positive to more than one of the 16 mould allergens. 2) According to the number of positive RASTs, the patients were divided into 3 groups, i.e. group 1 with more than five, group 2 with less than four and group 3 with zero. The ratio of patients with severe and moderate asthma to the total subjects was not significantly different between three groups before admission, but significantly high in group 1 and group 2 in order compared to groups 3 (chi 2(4)df = 18.81, p less than 0.005) one year after admission. This tendency was already apparent even one month after admission. 3) The frequency of positive RASTs for mould allergens was higher in patients with atopic dermatitis than in those without it. From these results, positive RAST for mould allergen seems to have considerable influence to intractable asthma and atopic dermatitis in young asthmatic patients. PMID- 2260928 TI - [The standard level of IgE RIST and eosinophil counts in 0-year old allergic children according to multiple factor analysis type II]. AB - We specified three standard levels of IgE RIST (10, 20, 60 IU/ml) for the ninety four (94) allergic clients of 0-year infants, who classified with three groups. Each group was furthermore divided in two groups such as a group under the standard level and a group exceeding the level respectively. Next, using the Multiple Factor Analysis Type II, we examined quantitative analysis that each of three classified groups was influenced on 12 allergic factors of sex, existence and inexistence of wheezing and atopic dermatitis, family history of allergic diseases, eosinophil counts. IgE RAST scores and antibody titers against egg white, milk and soybean, IgE RAST scores to Dermatophagoides farinae, while the we discussed how the standard levels were adequately reacted to the analysis. As a results, strong allergic factors which influenced the three groups commonly were two factors of IgE RAST scores to egg white and D.f. In particular, the factor which influenced the group of 10 IU/ml standard level was eosinophil counts and family history of allergic diseases. Furthermore, the strong factors which influenced the group classified on 60 IU/ml standard outstandingly appeared in IgE RAST scores to soybean, however, we did not find any difference between three groups. On the other hand, when we specified the standard level at 100/mm3, 200/mm3, 400/mm3 in regard to the eosinophil counts under the same method and examined results, we found strong allergic factors which influenced family history of allergic diseases. IgE RAST scores to egg white and soybean. However, the study scarcely recognize any difference between the three groups. PMID- 2260929 TI - [Study on specific IgE antibodies in pediatric allergic patients by CAP system]. AB - The CAP system is a new method to detect specific IgE antibodies and is an advanced method of the traditional paper disc RAST. Our result suggests a significant correlation between scores obtained with the CAP system and those with the traditional RAST. Since specific IgE antibodies against multiple allergens can be measured with the CAP system, we studied 5 food allergen specific IgE antibodies (Fx5) in cases of infantile atopic dermatitis. This study indicates a good correlation between the Fx5 scores and clinical symptoms of these patients. Thus, it is concluded that the CAP system is useful for screening IgE antibodies against multiple food allergens in cases of infantile atopic dermatitis. PMID- 2260930 TI - [Posture and circadian variations in serum theophylline concentrations]. AB - We have reported that the morning mean rate of absorption (ka) in immediate release aminophylline tablet is significantly faster than the evening one without any obvious change in AUC, the distribution (Vd), the rate of elimination (kel) or the elimination half-time (t1/2) and this altered absorption is a cause of circadian variation of theophylline concentrations with sustained-release preparations. Now, we examined the effect of posture on theophylline absorption. Seven asthmatic children were given immediate release aminophylline tablets at the same time in the morning on two separate occasions. On one day they remained standing and on the other lying. Serum theophylline concentration was measured at 0, 0.5, 1, 2, 3, 4, 5 hours after dosing. Mean theophylline levels were higher in the standing position at all time and only the mean rate of absorption (ka) was significantly faster without any obvious change in parameters of pharmacokinetics. This result was almost consistent with differences of day and night theophylline kinetics. We conclude that slowness of absorption in the evening is mainly induced by difference in posture. PMID- 2260931 TI - [Effect of specific desensitization therapy in combination with an immunopotentiator, Neurotropin, on perennial nasal allergy--with special reference to mite specific IgG and IgG4 antibody levels]. AB - We treated perennial nasal allergy with specific desensitization in combination with or without Neurotropin injections (NSP) from March 1983 to September 1984, and analyzed blood anti-mite IgG and IgG4 levels in relation to therapeutic efficacy. Desensitization and NSP were given once a week and seventy subjects (33 from the desensitization group and 37 from the desensitization + NSP group) were evaluated at 24, 36 and 48 weeks. 1) In total cases clinical usefulness showed no significant difference between the desensitization group and combined group at 24 weeks, while in "useful or more" cases significantly better results were attained in the latter at 24 weeks and 48 weeks (p less than 0.05, respectively). 2) Dermatophagoides pteronyssinus (D.p.) specific IgG antibody showed no significant difference between both groups as well as in each group during the overall examination period. 3) In total cases both D.p. specific and D. farinae (D.f.) specific IgG4 were significantly higher in the combined group at 24 and 36 weeks (D.p.: p less than 0.01 and D.f.: p less than 0.05, respectively), whereas in "useful or more" cases only D.p. specific IgG4 showed a significant elevation in the combined group at 24 weeks (p less than 0.05). These results suggest that specific desensitization in combination with NSP can promote early production of mite specific IgG4, which tend to rise in correlation with clinical efficacy. PMID- 2260932 TI - [Mitral valve prolapse in infective endocarditis. Incidence and characteristics]. AB - PURPOSE valve prolapse (MVP) cases, complicated with infective endocarditis (IE), seen at a cardiologic reference hospital. METHODS: The MVP cases were diagnosed within a series of 276 cases of IE without previous cardiac surgery with clinical echocardiographic criteria. We emphasised in our study; a) incidence; b) age and sex distribution; c) risk factors for IE; d) clinical-bacteriological data; e) echocardiographic features; f) therapeutic aspects; f) evolution and complications. RESULTS: a) We diagnosed 40 (14.4%) cases of MVP; b) mean age of 40.6 years, with 29 men (72.5%); c) dental procedures without prophylactic antibiotic-therapy in seven patients (17.5%), mitral regurgitation in 33 (82.5%), mitral valve redundancy in six (15%); d) fever was found in all patients (100%), cachexia was diagnosed in eight (20%), polyarthritis in six (15%) and congestive heart failure in six (15%). A systolic murmur of mitral regurgitation was found in all the patients and a nonejective click was encountered in four (10%), a Streptococcus was cultivated in 30 (75%), Staphylococcus in three (7.5%) Haemophilus sp in three (7.5%) Peptostreptococcus products in one (2.5%) and negative in three (7.5%) patients; e) echocardiographic signs of vegetation in 23 (57.5%), mitral regurgitation in 33 (82.5%), rupture of mitral chordae in 11 (27.5%) and mitral redundance in six (15.2%); f) 37 (92.5%) patients were medically treated and three (7.5%) required surgery; g) we registered in the hospital evolution: stroke in 10 (25%) and noncerebral mycotic aneurysm in 2 (5%) cases, two patients died (5%), one due to a hemorrhagic complication after surgery of bioprosthesis implantation and another of rupture of a cerebral mycotic aneurysm. CONCLUSION: The MVP was frequent in the population of patients with IE with of patients with mitral regurgitation, and male with mean age greater than the other cases. We observed low incidence of surgical need (7.5%) and lethal outcome (5%) but frequent (25%) neurological complications. PMID- 2260933 TI - [Comparative study of cardioplegia and intermittent cross-clamping in myocardial revascularization surgery]. AB - PURPOSE: To compare the effects of two methods for myocardial preservation during coronary artery by pass graft (CABG): the intermittent aortic cross-clamping (IACC) and the cold hyperkalemic solution (CHS). PATIENTS AND METHODS: One hundred and sixty-three patients operated for CABG between October/83 to May/84 were studied retrospectively. Those operated in emergency situations, reoperations and those who required concomitant additional procedures were excluded. The surgical technique used in both groups was essentially the same. Group I comprised 93 cases (40-70 years-old, median 57.7% y; 86% male) in which IACC were used. Group II comprised 70 cases (37-72 years old, median 67.7 y; 80% male) in which CHS (St. Thomas) was injected into the aortic root. The patients were evaluated in the immediate postoperative period at 3, 6, 12 months and then in variable periods until the 61 months of late follow-up. Myocardial ischemia and infarction, the use of drugs and the hospital time recovery were evaluated. The occurrence of symptoms, return to work, physical capacity, reinternations, reoperations and late deaths were evaluated in the late follow-up. RESULTS: During hospital period, no death was observed. Perioperative myocardial infarct was similar in both groups (group I = 2.1% and group II = 1.4%) statistical difference in the others parameters was observed. Of 95.5% of the patients who had postoperative observations, 80% had a late follow-up ranged from 30 to 61 months (median 38 months). One patient of each group had a cardiac death. In both groups (group I--1 patient and group II--4 patients) coronary insufficiency symptoms related were present and no statistical difference in the others parameters was observed. CONCLUSION: CHS or IACC were efficient and similar methods for myocardial protection in an elective group of patients submitted to a CABG in the immediate and late follow-up. PMID- 2260934 TI - [Predictive value of programmed ventricular stimulation after myocardial infarction]. AB - PURPOSE: To find out whether is there a relation between electrophysiology laboratory ventricular arrhythmias through programmed ventricular stimulation, and the occurrence of relevant clinical events, particularly, sudden death, in patients victims of first episode of myocardial infarction. PATIENTS AND METHODS: Twenty-seven patients (all males) who suffered non-complicated first myocardial infarction, with age varying from 47 to 70 (mean 54 +/- 6) years were prospectively and consecutively studied. Upon consent, patients were at first submitted to conventional cinecoronaryography and to programmed ventricular stimulation utilizing the S2, S3, S4 protocol, 30 days after infarction. Moreover, patients were submitted to continuous electrocardiographic (Holter system), exercise test, and radioisotopic studies for left ventricle ejection fraction (phase I). The last three studies were subsequently repeated at 6 and 12 months (phases II and III), respectively. RESULTS: All patients had ventricular arrhythmia induced, and according to the kind of response, patients were grouped into: group I--repetitive ventricular response, RVR, nine (33.5%) patients; group II--non sustained ventricular tachycardia. NSVT, eight (29.5%) patients; group III--sustained ventricular tachycardia SVT, ten (37%) patients. The patients of three groups, when submitted to electrocardiographic exercise test and Holter system studies, revealed complex arrhythmias in all phases. One patient of group II suddenly died at home, and another was injured with syncope, whereas in group III, two suddenly died, one at home and the other at the admission to the hospital, after an acute myocardial infarction. All patients but one of group I, who had a non-fatal reinfarction, showed preserved ventricular function. CONCLUSION: Holter system and electrocardiographic exercises test revealed complex dysrhythmia in the tree phases of the study, independently of the induced response; C--Holter system and electrocardiographic exercise test studies revealed no relation. between sudden death and the kind of ventricular induced response or complex arrhythmia. Ventricular arrhythmia induced with S2, S3 and S4 protocol in patients with preserved ventricular function seems to indicate results without predictive value for cardiac sudden death. PMID- 2260935 TI - [Malignant diphtheric myocarditis]. AB - PURPOSE: In the current study we analyzed clinical evolution and therapeutic aspects of malignant diphtheric myocarditis. METHODS: Fourteen patients with primary diagnosis of diphtheria were prospectively evaluated. Cardiac involvement was detected after 11.5 (mean) days. The diagnosis of diphtheric myocarditis was done in clinical basis. RESULTS: Seven (50%) patients died. Cardiac failure was a common finding in all cases. Complete A-V block was identified in eight (57%) patients. Temporary pacemaker was implanted in 10 cases, six of them died due to myocardial failure. Definitive pacemaker was necessary in two patients with persistent complete A-V block after one-month follow-up. One patient with atrial fibrillation died with sepsis. Respiratory infection was the commonest extracardiac complication (six cases) and two patients developed Guillain-Barre syndrome. We also identified neurologic, renal and adrenal complications. CONCLUSION: Cardiac rhythm disturbances in diphtheric myocarditis are associated with high probability of necessity of temporary pacemaker and high mortality. Definitive pacemaker can be implanted in persistent complete A-V block. PMID- 2260936 TI - [Prenatal diagnosis of congenital heart diseases and cardiac arrhythmias by Doppler echocardiography]. AB - PURPOSE: To detect in prenatal life fetal arrhythmia and congenital heart disease. We performed fetal echocardiography following classical indications according to the literature. PATIENTS AND METHODS: Two-dimensional echocardiography associated with M-mode and Doppler was performed in 200 patients according to the indications: maternal diabetes, fetal arrhythmia, maternal congenital heart disease, previous fetus with cardiac defect, intrauterine growth retardation, nonimmune fetal hydrops, rubeola, isoimmunization, fetal malformation by ultrasound, polyhydramnios, gemelarity, oligohydramnios, maternal ingestion of drugs, lupus and others. RESULTS: Structural abnormalities of the heart were found in 6 cases and associated with bradiarrhythmia in 5 cases (total of 5.5%). Fetal arrhythmias without cardiac malformation were found in 35 cases (17.5%) and premature atrial contractions were the most frequent. CONCLUSION: The findings in this study indicate that it is possible the accurate definition of the cardiac anatomy and function. We have emphasized the method trying to spread it, objecting to improve assistance to the fetus and newborn with arrhythmias and/or congenital heart disease. PMID- 2260937 TI - [Hemorrhagic infarction due to myocardial reperfusion. Report of 4 cases]. AB - Four different clinical cases in which the myocardial reperfusion occurred after acute myocardial infarction, and was followed by significant hemorrhagic ventricular damage. We discuss some possible etiologic mechanism of the problem and present some methods of myocardial protection which are meant to lessen those negative effects of the reperfusion. We conclude setting the difficulty to determine the critical moment after which the myocardial reperfusion turns inefficient or even harmful. PMID- 2260938 TI - [Traumatic ventricular septal defect. A case report]. AB - A 34 years old woman, without previous cardiac symptoms, suffered a closed thoracic trauma in a car accident. Three days after presented dyspnea and orthopnea. Physical examination revealed a systolic murmur consistent with ventricular septal defect (VSD). Doppler echocardiography and angiography confirmed the presence of a muscular VSD with severe left-to-right shunt. Surgical intervention was indicated and VSD closure was performed with a patch, through a right atrium approach. Third degree atrioventricular block developed after surgery and a definitive pacemaker was implanted. The patient is asymptomatic and without murmurs in postoperative follow-up. PMID- 2260939 TI - [Surgical treatment of right ventricular fibroma in infants. Report of 2 cases]. AB - Two patients under 8 months of age, with right ventricular fibroma, presented with clinical manifestations of pulmonary stenosis. The diagnosis was established in one by echocardiography and in the other by echocardiography. CT scan and angiocardiographic study. The patients were operated and the tumors were successfully resected. PMID- 2260940 TI - [Management of hypertension in the elderly]. PMID- 2260941 TI - [Doppler echocardiographic evaluation of the diastolic function in the left ventricule]. PMID- 2260942 TI - [Endomyocardial fibrosis. A new surgical approach]. PMID- 2260943 TI - [Myocardial protection]. PMID- 2260944 TI - [Intrauterine echocardiography]. PMID- 2260945 TI - [Anatomic variation of the mitral valve]. PMID- 2260946 TI - [Lymphatic system of the heart. A little known field]. PMID- 2260947 TI - [A micromesoscopic study of human arachnoid granulations]. AB - The functional anatomy of the arachnoid granulations of the upper sagittal sinus was studied by means of micromesoscopic techniques in order to contribute to elucidating aspects of drainage pathways of the cerebrospinal fluid through their fibrous components. The arrangement of fibrous elements was analysed at the base of the peduncle, peduncle, middle and apex of granulation. The analysis of serial sections shows collagen bundles at the base of the peduncle with a predominantly circular morphology, longitudinally directed towards the peduncle's longest axis. These bundles arise in the middle of the granulation, them branch off towards its apex and periphery. The elastic bundles present an arrangement similar to that described for collagen bundles, delimiting with such bundles intercommunication channels from the base of the peduncle up to the apex of the granulation. Bundles of reticular fibers arranged in between the collagen meshes were found at the base of the peduncle. The fibrous capsule of granulation is composed of collagen bundles and a small number of elastic fibers. PMID- 2260948 TI - [Purulent meningitis in children during the 1st year of life]. AB - A series of 169 children with diagnosis of acute purulent meningitis during the first year of life was studied. Clinical and neurological findings are discussed, and for this purpose patients were separated in subgroups concerning their age. The great frequency in suckling until 6 months of age is emphasized. PMID- 2260949 TI - [Bacterial meningitis in infants: neurological aspects]. AB - Clinical, neurologic and laboratory aspects of bacterial meningitis in the newborn infant are critically reviewed taking into account author's experience. Pathophysiologic data on acute phase phenomena in the CNS are analysed for this purpose. PMID- 2260950 TI - [Photosensitivity in primary and secondary epilepsies]. AB - A retrospective study was performed on 34 patients with photosensitivity detected on the electroencephalogram. This group was compared to an aleatory sample, with 218 patients. The objectives were to evaluate the photosensitivity and: type of epilepsy, age of onset of seizures, sex ratio, frequency of seizures, and family history. PMID- 2260951 TI - Unilateral neglect syndrome: clinical and topographic study of 20 subjects. AB - Twenty patients with unilateral neglect syndrome were studied. They were 10 males and 10 females, and they ranged from 29 to 76 years of age. All were submitted to a CAT scan of the brain. Based on the findings in our sample we drew the following conclusions: the extinction phenomenon was a constant manifestation of unilateral neglect; the line crossing test proved to be most efficient for the identification of visual neglect; the right parietal lobe was the anatomical region most often involved in the unilateral neglect syndrome. PMID- 2260952 TI - Auditory extinction and dichotic listening CV task in cerebral infarction: preliminary report. AB - Six stroke patients were studied using a dichotic listening CV task, 4 with left hemisphere infarction, 2 with right hemisphere infarction. It was observed a "lesion-effect", a shift of hemisphere prevalence to the side opposite a brain lesion. The authors suggest that the lesion-effect can be explained by the auditory extinction phenomenon at the linguistic level. PMID- 2260953 TI - [Asymptomatic polyneuritis: a starting point for the diagnosis of diabetes]. AB - Eighty consecutive neurological ambulatory patients with various symptoms are presented. All patients with a history of diabetes or alcoholism were excluded. The group was composed of 54 females and 26 males ranging in age from 16 to 67 years. Neurological examination showed at least one peripheral abnormal finding in all patients. Absence of Achilles reflexes, impairment of tactile and vibratory sensibility in the distal portions of the legs and dysesthesia were the most frequent alterations. All patients showed normal fasting blood sugar and were submitted to the oral glucose tolerance test. Some evidence of abnormal glucose tolerance was present in 41 patients (51.25% of the entire group). Thus, we suggest that polyneuritis, misinterpreted as late complication, is indeed an integral part of the syndrome of diabetes and may be its very first objective sign. In conclusion, it is assumed that all patients with evidence of objective polyneuritis should be thoroughly tested for abnormality of glucose tolerance. PMID- 2260954 TI - [Neurocysticercosis: incidence in the state of Rio de Janeiro]. AB - One hundred patients with neurocysticercosis born and residents in Rio de Janeiro State were studied from September 1981 to December 1989. The approximate incidence rate of one case per month shows that the disease is not rare in this State of Brazil. PMID- 2260955 TI - [Hemifacial spasm: results of microvascular decompression in 53 patients]. AB - In a ten year period 53 patients with hemifacial spasm were submitted to 54 microvascular decompression procedures in the posterior fossa. The technique was the same developed by Jannetta and the initial surgical results were considered excellent in 91% of the cases. The follow-up ranges from 60 days to 7 years, with 40 patients followed for more than two years and 16 for more than five years. Only one patient presented late recurrence of the spasms. There was no death nor serious complications which were usually transient and related do the seventh and eight nerve. In four patients we found no compression of the nerve root. We concluded that no matter what the causes of hemifacial spasm or the mechanisms of action of the surgery are the results of microvascular decompression are excellent and superior to all other clinical and surgical methods of treatment. PMID- 2260956 TI - [Chronic subdural hematoma as a complication of ventriculoperitoneal shunts]. AB - Nine cases of chronic subdural hematoma occurring after the insertion of ventriculo-peritoneal shunts are described. Three patients were children, two were adults with stenosis of the Sylvian aqueduct, and the last four had normal pressure hydrocephalus. Patients with chronic hydrocephalus were initially treated with burr holes associated to transient occlusion of the distal catheter of the diversion in order to promote reexpansion of the compressed hemisphere. Two shunt-dependent patients were successfully treated with a concurrent subdural peritoneal shunt. In two cases a higher pressure shunt was inserted, and in another craniotomy with membranectomy was required to treat persistent subdural fluid accumulation. One patient died due to infectious complications of multiple procedures. PMID- 2260957 TI - Cerebral aneurysms: assessment of 377 cases (1956-1982). AB - A review of 177 patients with cerebral aneurysms is made, out of whom 106 with ruptured aneurysms were examined, whose operational timing and prognostic chances were well documented (group B, 1979-1982) and in part updated to 1984. Furthermore, relevant data of a previous series of 200 cases of cerebral aneurysm, treated between 1956-1978 were used (group A). The patients were graded according to Hunt and Hess, assessing the risks involved. The percentages of recurrent bleeding were in group A 36.5% and 28% in group B. The incidence of vasospasm (as seen in angiography) was in group B 39.6% (42/106 patients). The highest rate of vasospasm in the spasm group division B was found to occur in the second and third week after subarachnoid haemorrhage and amounted to 64.7% and 62.5%. A pre-operatively present vasospasm had no negative effects on the mortality rate, but influenced the outcome for the survivors effectively. The total mortality in group A was 22.5% and in group B 11.7%. Timing of the operation among patients in Hunt and Hess-grades I and II needs to discussion. The surgical position of patients in grade V is also certain. What remains to be discussed and needs attention is grade III and patients in grade IVa. Here the time of operative intervention must be planned individually depending on the course of the neurological status. PMID- 2260958 TI - Management of giant aneurysms. AB - Technical aspects and anatomical difficulties involved in the management of this entity and the risks associated give giant aneurysms a special place in the treatment of aneurysms as a whole. The direct attack needs careful planning and the right choice of instruments, especially clips. In spite of the progress in recent years, the rate of mortality is still very high. The indirect approach requires in many cases the occlusion of a major cerebral vessel, which in some cases could result in cerebral ischemia. However, by means of extra-intracranial by-pass operation this risk could be reduced. The method of balloon embolisation has progressed recently. This procedure brings the least discomfort to the patient. Results of this method of treatment must be observed critically for future assessment. PMID- 2260959 TI - Shy-Drager syndrome: a case report with polysomnography. AB - The authors report a case of Shy-Drager syndrome in a 53 year-old male patient. Autonomic failure was made evident by physical examination as well as laboratory tests. A sleep recording showed decreased percentage of REM sleep and apneas of the central type. The possible mechanisms for this sleep disorder are discussed. PMID- 2260960 TI - [Hyperparathyroidism simulating Creutzfeldt-Jakob disease]. AB - A 45 years-old woman presented with loss of initiative and memory, motivated cry and behaviour disturbance with childish traits, quickly progressive along 6 months until total apathy. An EEG showed periodic activity with bilateral triphasic waves against a flattened background activity suggesting Creutzfeldt Jacob disease (CJD), but investigation for treatable causes of dementia disclosed hypercalcemia and hypophosphatemia. Further investigation showed a mass at the thyroid region that at surgery was identified as an oxyphilic cells adenoma. With electrolyte disturbance correction and posterior surgery there was normalization of both EEG and clinical status. Though it was previously reported mental confusion and EEG alteration associated with hyperparathyroidism we do not know of any previous case of confusion associated with periodic activity in EEG as in this disease. Hyperparathyroidism should be a differential diagnosis in every "de novo" case of CJD. PMID- 2260961 TI - [Bilateral abducens nerve palsy in nasopharyngeal carcinoma]. AB - We report a case of bilateral abducens palsy as initial finding in nasopharyngeal carcinoma. Possible mode of involvement is discussed. Only one case has been reported in the past. PMID- 2260962 TI - [Brain death: criteria for its clinical diagnosis]. PMID- 2260963 TI - Bovine beta-mannosidase deficiency. AB - A fatal inherited glycoprotein storage disorder is described in Salers cattle which affects both sexes. Affected calves are unable to stand at birth, have a marked intention tremor, markedly enlarged kidneys, decreased white matter in all areas of the brain, and cytoplasmic vacuolation in multiple cell types of multiple tissues with nervous, renal, lymphoid and thyroid tissues most severely affected. Affected calves were grossly deficient in lymphocyte and brain beta mannosidase activity and had markedly reduced but not deficient activity in liver and kidney. A test mating of obligate carriers produced three genotypes: affected, carrier, non-carrier in essentially the expected ratio of 1:2:1, consistent with autosomal recessive inheritance. PMID- 2260964 TI - Purification and crystallization of 15-lipoxygenase from rabbit reticulocytes. AB - We report a new purification of rabbit reticulocyte 15-lipoxygenase that has resulted in the first crystallization of a mammalian lipoxygenase. The enzyme was purified to homogeneity (greater than 98% pure by SDS-PAGE) using high pressure liquid chromatography on hydrophobic-interaction, hydroxyapatite and cation exchange columns. Crystals were grown by the vapor diffusion method from concentrated solutions of the protein in sodium phosphate buffer, pH 7.0. The hexagonal, rod-shaped crystals were on average 0.09 mm x 0.09 mm x 0.4 mm, with approximate unit cell dimensions of a = b = 260 A, c = 145 A. The crystals diffract to 5 A resolution. PMID- 2260965 TI - Transformation by ras oncogene induces nuclear shift of protein kinase C. AB - We measured protein kinase C (PKC) activity in normal and ras-transformed Balb/3T3 fibroblasts; cytosolic and nuclear-associated PKC activity was determined either as phorbol ester binding, PKC-dependent phosphorylation of histone III-S, or phosphorylation of endogenous nuclear proteins. Results demonstrate that ras-transformed fibroblasts show down-regulation of cytosolic PKC accompanied by increase of nuclear-associated PKC. These results provide evidence linking transformation to PKC nuclear shift with consequent phosphorylation of nuclear proteins. PMID- 2260966 TI - A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. AB - LNCaP prostate tumor cells contain an abnormal androgen receptor system. Progestagens, estradiol and anti-androgens can compete with androgens for binding to the androgen receptor and can stimulate both cell growth and excretion of prostate specific acid phosphatase. We have discovered in the LNCaP androgen receptor a single point mutation changing the sense of codon 868 (Thr to Ala) in the ligand binding domain. Expression vectors containing the normal or mutated androgen receptor sequence were transfected into COS or Hela cells. Androgens, progestagens, estrogens and anti-androgens bind the mutated androgen receptor protein and activate the expression of an androgen-regulated reporter gene construct (GRE-tk-CAT). The mutation therefore influences both binding and the induction of gene expression by different steroids and antisteroids. PMID- 2260967 TI - The effect of bovine lactoferrin on muscle growth in vivo and in vitro. AB - Lactoferrin was found to be a potent stimulator of proliferation for L6 myoblasts. Both apo and holo-forms of lactoferrin were equipotent. By contrast, only the holo-form of transferrin (a structurally related iron binding protein) stimulated proliferation, apo-transferrin was without activity. Holo-transferrin was also less stimulatory than lactoferrin. Purified lactoferrin was administered to mature female rats and to neonatal rats by daily subcutaneous injection to determine if there was a measurable effect on muscle cell growth in vivo. Results from the in vivo studies suggest that lactoferrin has little or no effect on muscle cell growth in the whole animal. PMID- 2260968 TI - Fractionation of the ribosome inactivating protein preparations with triazine dyes. AB - Aspergillins are ribosome-inactivating proteins (RIPs), isolated from several strains of Aspergillus. The interaction between Cibacron Blue F3GA and two members of this family, alpha sarcin and mitogillin, and other RIPs of type I, was studied. Alpha sarcin retention depended on pH and ionic strength. By chromatography on Affi-Gel Blue in mild experimental conditions, mitogillin and PAP-I did not interact with the dye, whereas 40% of alpha sarcin and 70-90% of briodin, RTA and gelonin were recovered in the bound fraction. In all cases, the major fraction showed a higher toxicity level in protein synthesis inhibition assays. The unbound alpha sarcin, conjugated with the anti-ovarian carcinoma monoclonal antibody MOv17, showed on OVCA 432 a cytotoxicity which was 900 times higher than that exerted by the alpha sarcin alone. PMID- 2260969 TI - N-3 polyunsaturated fatty acids enhance cholesterol efflux from human fibroblasts in culture. AB - Normal human skin fibroblasts were incubated in medium supplemented with 60 micrograms/ml linoleic acid (18:2n6) or eicosapentaenoic acid (20:5n3). After five days, cells lipids were enriched with linoleic acid or with docosapentaenoic acid (22:5n3). The HDL-mediated efflux of cholesterol from cells enriched with n 3 polyunsaturated fatty acids (PUFAs) was twice as fast as the rate of efflux of cholesterol from cells enriched with n-6 PUFAs. This suggests that the fatty acid composition of cellular lipids affects cholesterol efflux. The faster efflux when cells contain n-3 PUFAs may account for part of the reduction in risk of coronary disease with increases in dietary n-3 PUFAs (fish oils). PMID- 2260970 TI - Interleukin-1: a cytokine that has potent antisecretory and anti-ulcer actions via the central nervous system. AB - The present study was performed to determine if interleukin-1 (IL-1) acts as a chemical messenger in the central nervous system (CNS) regulation of gastric secretion and ulcer formation, using male Wistar rats. The central injection of IL-1 dose-dependently inhibited gastric acid secretion in pylorus-ligated rats at 100 times smaller doses than the peripheral injection of the cytokine. The action of IL-1 was long-lasting because its antisecretory effect was still evident at 8 hr after injection. Furthermore, it was observed that pretreatment with central IL-1 dose-dependently suppressed the development of gastric ulcers induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly suggested for the first time that IL-1, a cytokine produced by activated monocytes/macrophages, acts centrally in the brain to exert gastric antisecretory and anti-ulcer actions. PMID- 2260971 TI - Biological characterization of human brain natriuretic peptide (BNP) and rat BNP: species-specific actions of BNP. AB - We examined the diuretic-natriuretic activities of rat BNP and human BNP in anesthetized rats in vivo and their vasorelaxant activities for rat thoracic aorta and porcine coronary artery in vitro. Rat BNP was almost equipotent to rat ANP in diuresis and natriuresis with relative potencies of 1.6 and 2.5, respectively, while human BNP exerted no significant activity. Rat ANP, rat BNP and human BNP relaxed PGF2 alpha-contracted rat aortic strips with IC50 values of 0.62, 0.64 and 12.1 nM, respectively, while they relaxed PGF2 alpha-contracted porcine coronary arteries with IC50 values of 0.04, 1.10 and 0.02 nM, respectively. These results strongly suggest that the biological action of BNP is species-specific. PMID- 2260972 TI - Mercury chloride as a possible phospholipase C activator: effect on angiotensin II-induced [Ca++]i transient in the rat early proximal tubule. AB - In our previous report (Biochem. Biophys. Res. Commun. 165(3), 1221-1228, 1989), we have demonstrated the biphasic increase of intracellular free calcium concentration ([Ca++]i) induced by angiotensin II (ANG II) in isolated rat early proximal tubule (S1). The present study was undertaken to determine the effect of HgCl2 on ANG II-induced [Ca++]i increase using Fura-2. HgCl2 (10(-10) M2-10(-8) M) potentiated the [Ca++]i increase induced by ANG II (10(-11) M) in a dose dependent manner. To determine the mechanism of stimulatory effect by HgCl2 on ANG II-induced [Ca++]i increase, nephron segments were pretreated with 10(-4) M propranolol, a phospholipase C inhibitor. The stimulatory effect by 10(-9) M HgCl2 in 10(-11) M ANG II-induced [Ca++]i increase was completely inhibited by propranolol. Moreover, 10(-4) M propranolol completely blocked the stimulatory effect of HgCl2 on ANG II-mediated IP3 production. This study suggests for the first time that HgCl2 stimulates the [Ca++]i increment induced by ANG II, possibly through an activation of phospholipase C. PMID- 2260973 TI - Leukotriene A4 hydrolase is a zinc-containing aminopeptidase. AB - A comparison of amino acid sequences revealed that leukotriene A4 (LTA4) hydrolase is homologous to various types of aminopeptidases. Consistently with the finding, the purified LTA4 hydrolases from both human and guinea pig sources contained equimolar zinc ion, as determined by atomic absorption spectrometry. The enzyme had a significant amount of aminopeptidase activity toward synthetic peptide substrates. Both LTA4 hydrolase and aminopeptidase activities were inhibited by o-phenanthroline, p-chloromercuribenzoic acid, and Leu-thiol with similar IC50 values. Co-purification as well as co-immunoprecipitation of both enzyme activities with an affinity-purified antibody against LTA4 hydrolase strongly suggest that the two enzyme activities reside in a single protein. PMID- 2260974 TI - The complete amino acid sequence of the mature form of rat sepiapterin reductase. AB - The partial amino acid sequence of rat sepiapterin reductase was determined using peptides generated by cleavage of the S-carboxyamidomethylated protein with Achromobacter protease I, cyanogen bromide, chymotrypsin or BNPS-skatole. The protein began with N-acetyl methionyl residue at the N-terminus and ended with isoleucyl residue at the C-terminus. The present results essentially coincided with the amino acid sequence predicted from the nucleotide sequence of the cDNA recently reported by Citron et al. (Proc. Natl. Acad. Sci. USA 87, 6436-6440 (1990)), clarified the processing event during the biosynthesis and provided the complete amino acid sequence of the mature form of the enzyme. PMID- 2260975 TI - Rapid confirmation and revision of the primary structure of bovine serum albumin by ESIMS and Frit-FAB LC/MS. AB - Incorrectness of the amino acid sequence of bovine serum albumin (BSA) was suggested from the observed molecular weight of BSA obtained by electrospray ionization mass spectrometry (ESIMS). Lack of a tyrosine residue in the position of 156th was found rapidly, by the combination of frit-fast atom bombardment mass spectrometry/liquid chromatography (Frit-FAB LC/MS), automated Edman degradation and tandem mass spectrometry (MS). Then it turned out that BSA is composed of 583 amino acid residues, and that its average molecular weight is not 66267.1, and it is corrected to 66430.3. Moreover the amino acid sequence of the positions of 94th and 95th was corrected to -QE- by using automated Edman degradation method. PMID- 2260976 TI - A selective assay for endooligopeptidase A based on the cleavage of fluorogenic substrate structurally related to enkephalin. AB - A novel quenched fluorescence substrate, QF-ERP7 (Abz-G-G-F-L-R-R-V-EDDn), structurally related to enkephalins, proved to be suitable for assaying the endooligopeptidase A (E.C.3.4.22.19) activity. The enzyme only splits the L-R bond (Km 1.75 microM, Kcat 8.25 s-1), a reaction efficiently blocked by anti endooligopeptidase A antibodies and by inhibitor and alternative substrates of the enzyme. Evidences based on the action of inhibitors and on the analysis of QF ERP7 fragments demonstrated that endooligopeptidase A contributes with 100% of the QF-ERP7 cleaving activity found in the cytosol of rabbit brain homogenates and with 85% of that recovered in the membrane fraction. Homologous substrates, Abz-G-G-F-L-R-R-EDDn and Abz-G-G-F-L-R-EDDn, were resistant to hydrolysis. The convenience and sensitivity of the fluorimetric assay based on the QF-ERP7 moiety offers several advantages compared with previously described painstaking procedures for endooligopeptidase A activity measurements, what will certainly contribute to further our understanding of the role of this enzyme on the peptide hormone metabolism. PMID- 2260977 TI - Characterization of the cDNA encoding proopiomelanocortin in the frog Rana ridibunda. AB - In the amphibian pars intermedia, secretion of proopiomelanocortin (POMC)-derived peptides is controlled by multiple factors including classical neurotransmitters and neuropeptides. To pursue questions concerning the regulation of POMC gene expression in Rana ridibunda, we have isolated and characterized a full-length cDNA for frog POMC. A cDNA clone isolated from a frog pituitary library contains an open-reading frame of 780-bp that predicts a 260 amino acid POMC protein. The structure of frog POMC demonstrates considerable amino acid sequence similarity with POMC from other species. In particular, the sequence of alpha-melanotropin (alpha-MSH) is identical in frog and all mammalian species studied so far, while adrenocorticotropin (ACTH) and beta-endorphin exhibit 79% and 84% homology with their human counterpart. Frog POMC contains only one potential asparagine-linked N-glycosylation signal (Asn-Ser-Thr) within the gamma-MSH domain. The alpha-MSH sequence is C-terminally flanked by the Gly-Lys-Lys amidation signal while the joining peptide is not amidate. PMID- 2260978 TI - Site-specific phosphorylation of a synthetic peptide derived from ribosomal protein S6 by human placenta protein kinases. AB - A synthetic peptide S6-21 (AKRRRLSSLRASTSKSESSQK) which contains the phosphorylated residues in the ribosomal protein S6 has been used as a substrate for two partially purified human placenta protein kinases. Two distinct classes of protein kinases which catalyze either amino terminal (AKRRRLSS) or carboxyl terminal (LRASTSKSESSQK) peptide phosphorylation were identified. Multiple sites were phosphorylated in each domain. A single protein kinase which catalyzed phosphorylation of sites in both domains was identified. Although growth factors are known to promote phosphorylation of S6 at five serine sites, no enzyme which could modify S6-21 to that extent was observed. PMID- 2260979 TI - Phosphorus-31 nuclear magnetic resonance spectroscopy reveals two conformational forms of chloroacetol phosphate-bound triosephosphate isomerase. AB - Chloroacetol phosphate covalently reacts with Glu-165 in the catalytic center of triosephosphate isomerase. Reaction of the enzyme with the substrate analogue results in two 31P resonances at 6.8 and 5.5 ppm. Dissociation with guanidinium chloride results in a single resonance at 4.5 ppm. Reassociation and redimerization of the triosephosphate isomerase-chloroacetol phosphate complex restores only the resonance at 5.5 ppm. The two 31P resonances appear to represent different conformations of the enzyme which are trapped upon reaction with the affinity label. PMID- 2260980 TI - Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase. AB - The cDNA encoding human ferrochelatase [EC 4.99.1.1] was isolated from a human placenta cDNA library in bacteriophage lambda gt11 by screening with a radiolabeled fragment of mouse ferrochelatase cDNA. The cDNA had an open reading frame of 1269 base pairs (bp) encoding a protein of 423 amino acid residues (Mr. 47,833) with alternative putative polyadenylation signals in the 3' non-coding regions and poly (A) tails. Amino acid sequencing showed that the mature protein consists of 369 amino acid residues (Mr. 42,158) with a putative leader sequence of 54 amino acid residues. The human enzyme showed an 88% identity to mouse enzyme and 46% to yeast enzyme. Northern blot analysis showed two mRNAs of about 2500 and 1600 bp for ferrochelatase in K562 and HepG2 cells. As full-length cDNA for human ferrochelatase is now available, molecular lesions related to erythropoietic protoporphyria can be characterized. PMID- 2260981 TI - Role of tryptophan 248 in the active site of tryptophanase from Escherichia coli. AB - Tryptophan 248, located in the active site of tryptophanase from Escherichia coli, has been replaced with phenylalanine by site-directed mutagenesis. Judging from CD and fluorescence spectra, the global structure of the mutant enzyme was found to be the same as that of the wild-type enzyme. The binding affinity of the mutant enzyme for the coenzyme pyridoxal 5'-phosphate (PLP) was reduced tenfold compared to the wild-type enzyme. Kinetic analyses under PLP-saturated conditions indicated that the Km values of the mutant enzyme for substrates are the same as those of wild-type enzyme but the kcat values are decreased to about 85%, which accounts for the overall activity decrease. These findings suggest that tryptophan 248 interacts closely with PLP and plays an important role in the catalytic reaction. PMID- 2260982 TI - Amino acid sequence of chicken calsequestrin deduced from cDNA: Comparison of calsequestrin and aspartactin. PMID- 2260983 TI - A novel mechanism for eukaryotic gene expression. The involvement of DNA tertiary structure in estrogen receptor recognition of its target nucleotide sequence. PMID- 2260984 TI - Characterization of neuropathy target esterase using trifluoromethyl ketones. AB - Neuropathy target esterase (NTE) is a membrane-bound carboxylesterase activity which is proposed as the target site in nerve tissue for initiation of organophosphate-induced delayed neuropathy. This activity is identified as phenyl valerate hydrolysis which is resistant to treatment with paraxon and sensitive to co-incubation with paraxon and mipafox. NTE preparations were obtained, which did not contain paraxon-sensitive or mipafox-resistant hydrolases, by selective reconstitution of detergent-solubilized NTE from chick embryo brain into asolectin vesicles during gel filtration. The topography of the catalytic site of NTE was then examined by investigating the inhibition of NTE by a series of 3 alkylthio- and 3-arylthio-1,1.1-trifluoro-propan-2-ones. These trifluoromethyl ketones were found to be rapidly reversible, competitive inhibitors of NTE with I50 values 1.3 x 10(-4) M to 4.9 x 10(-8) M. Correlation of I50 values with octanol/water partition coefficients (P), in the range of log P = 1.5 to 5.9. indicated that the optimal lipophilicity for NTE substrates and inhibitors is in the range of log P = 3.0 to 3.4. Electrophilic substitution at the meta position of aromatic rings increased the inhibitory capacity of these inhibitors, whereas substitution at the ortho position reduced inhibitory capacity. These results indicate both that a large hydrophobic pocket is closely associated with the catalytic residue of NTE, and that affinity for the active site is affected by steric and electronic parameters. PMID- 2260985 TI - Mouse renal cytochrome P450IIE1: immunocytochemical localization, sex-related difference and regulation by testosterone. AB - Cytochrome P450IIE1 is responsible for the metabolic activation of N nitrosodimethylamine and a variety of other chemicals. Renal P450IIE1 was shown previously to be regulated by testosterone in C3H/HeJ and BALB/c mice. The present study investigated the distribution of cytochrome P450IIE1 in the kidneys of C3H/HeJ and BALB/c mice. The amount of P450IIE1 was immunotitrated by immunohistochemistry using polyclonal antibodies against rat P450IIE1. Strong immunoreactivity was identified mainly in the cortical tubules, including proximal tubules and some tubules. Weak immunoreactivity was also observed in the outer medulla when higher concentrations of antibodies were used. Much higher immunostaining was observed in male mice than in female mice when identical antibody dilutions were used. The renal P450IIE1 level in females was elevated to the same level as that in males 24 hr after administration of testosterone. The results showed a specific cellular localization of cytochrome P450IIE1 in mouse kidney. The findings may lead to a better understanding of the site-specific renal toxicity and carcinogenesis due to the activation of chemicals by cytochrome P450IIE1. PMID- 2260986 TI - S-adenosylmethionine increases erythrocyte ATP in vitro by a route independent of adenosine kinase. AB - The mechanism by which S-adenosylmethionine (SAM) and adenosine (Ado) increase ATP levels in intact human erythrocytes in vitro has been compared. The use of erythrocytes from healthy controls and from subjects totally deficient in adenine phosphoribosyltransferase (APRT), plus inhibitors of adenosine kinase (AK) and adenosine deaminase (ADA) separately and together, has enabled us to demonstrate that this increment in ATP levels occurred via totally different metabolic routes. The results show that: (i) whilst the Ado-induced increment in ATP was AK dependent, that produced by SAM was independent of AK: and (ii) the SAM-induced increment in ATP was totally dependent on APRT and that some of the increment produced by Ado might also be APRT dependent. The above data are consistent with the metabolism of SAM to ATP by a route recently identified by us whereby ATP is formed from deoxyadenosine: namely binding to the enzyme S-adenosylhomocysteine hydrolase with subsequent release of adenine and further conversion to ATP via APRT. PMID- 2260987 TI - Pyretic action of low doses of gamma-hydroxybutyrate in rats. AB - gamma-Hydroxybutyrate (GHB) has been found to have a biphasic effect on body temperature with increased body temperature after low doses (5-10 mg/kg) and decreased body temperature after high doses (300-500 mg/kg). Brain levels of GHB between 30 and 60 min post-injection of GHB were not altered by the low doses (5 10 mg/kg), although a dose of 200 mg/kg produced a large increase in the brain concentration. PMID- 2260988 TI - Relationships between resistance to cross-linking agents and glutathione metabolism, aldehyde dehydrogenase isozymes and adenovirus replication in human tumour cell lines. AB - In a panel of 10 human tumour cell lines with no prior exposure to drugs in vitro, resistance to cisplatin correlated with resistance to the nitrogen mustard derivatives Asta Z-7557 (mafosfamide, an activated form of cyclophosphamide), melphalan and chlorambucil. Simultaneous treatment with DL-buthionine-S,R sulfoximine did not enhance the toxicity of cisplatin or Asta Z-7557, and no correlation was found between drug resistance and cellular levels of metallothioneins (as judged by sensitivity to cadmium chloride), glutathione (GSH), GSH reductase, GSH transferase, or gamma-glutamyltranspeptidase. The two cell lines most resistant to Asta Z-7557 expressed aldehyde dehydrogenase cytosolic isozyme 1, found also in normal ovary, but not isozyme 3. Treatment of resistant cells with cisplatin or Asta Z-7557 inhibited cellular DNA synthesis and replication of adenovirus 5 to a lesser extent than in sensitive cells. The virus could be directly inactivated by both drugs prior to infection, subsequent replication being inhibited to the same extent in sensitive and resistant cells. In contrast to Asta Z-7557 and other DNA damaging agents, cisplatin was much more toxic to adenovirus (D37 0.022-0.048 microM) than to cells (D37 0.25-2.5 microM). The adenovirus 5 mutant Ad5ts125 having a G----A substitution was even more sensitive to cisplatin (D37 7-8 nM) than wild type virus and another mutant. Cisplatin was detoxified less by sonicated resistant resistant cells than sensitive cells, as judged by inactivation of Ad5ts125 added to the reaction mixture. It can be inferred that (i) the major differences in cellular resistance to cisplatin and Asta Z-7557 in the present material did not involve enhanced DNA repair or protection by metallothioneins or GSH, but were associated with the ability to continue cellular and viral DNA synthesis during treatment, (ii) resistance was not associated with less template damage, and (iii) the adenovirus genome may be a suitable probe for predicting tumour resistance to cisplatin and for elucidating the DNA sequence dependence of cisplatin toxicity. PMID- 2260989 TI - Mechanism of leucovorin reversal of methotrexate cytotoxicity in human MCF-7 breast cancer cells. AB - Previous studies have suggested that metabolic inhibition by methotrexate (MTX) is multifactorial and that cytotoxicity can be reversed by the reduced folate leucovorin. In this report we investigated the mechanism of leucovorin rescue in the MCF-7 human breast cancer cell line. Cells were exposed to various concentrations of MTX (0.5, 1.0, 3.0, and 10.0 microM) for 24 hr followed by rescue with labelled leucovorin (0.5 to 50 microM). The changes in the intracellular folate pools 24 hr following the addition of leucovorin were quantitated by high-pressure liquid chromatographic methods. The changes in the folate pools during rescue were compared with the ability of various concentrations of leucovorin to affect cellular rescue from MTX using a cloning assay. Our studies show that the total labelled intracellular folate pools increased in a log-linear fashion with respect to leucovorin exposure concentrations up to 100 microM. The degree of accumulation at a given leucovorin concentration was not significantly different in the absence or presence of MTX over the concentration range of 0.5 to 10 microM. Individual folate pool levels (tetrahydrofolate, 10-formyl tetrahydrofolate, 5-formyl tetrahydrofolate, 5 methyl tetrahydrofolate, and 5,10-methylene tetrahydrofolate) reached those present in cells not exposed to MTX at concentrations of leucovorin that were not adequate to rescue the MTX-treated cells. With exposure to concentrations of leucovorin capable of rescue, the individual folate pool levels were up to twelve times greater than those found in untreated cells, consistent with competition for catalytic activity at folate-dependent enzymes in addition to dihydrofolate reductase. The dihydrofolate pool also increased with increasing leucovorin concentration: but, unlike the reduced folates, this oxidized folate reached a maximal level that was dependent on the MTX concentration to which the cells had been exposed. This suggests that competition between MTX and leucovorin occurs at the level of dihydrofolate reductase via a competitive interaction with dihydrofolate in this intact cell system. The ability of leucovorin and its metabolites to compete with direct inhibitors of dihydrofolate reductase and other metabolically important folate-dependent enzymes appears to be associated with leucovorin rescue. PMID- 2260990 TI - Enhancement of melphalan (L-PAM) toxicity by reductive metabolites of 1-methyl-2 nitroimidazole, a model nitroimidazole chemosensitizing agent. AB - Chemosensitization of bifunctional alkylators by misonidazole (MISO) and related nitroimidazoles in vitro has been shown to require hypoxic exposures. Presumably, reductive metabolism of the nitroimidazole under hypoxic conditions results in generation of a chemosensitizing intermediate(s) in a manner analogous to that described for the hypoxic toxicity of these compounds. In an attempt to identify these intermediates, we examined the ability of reductive metabolites of a model 2-nitroimidazole compound, 1-methyl-2-nitroimidazole (INO2), to enhance the toxicity of melphalan (t-PAM) in HT-29 human colon cancer cells. INO2 was a modest chemosensitizing agent, enhancing L-PAM only under hypoxic conditions. The 2-electron reduction product, 1-methyl-2-nitrosoimidazole (INO), was a potent chemosensitizer, enhancing L-PAM toxicity at micromolar concentrations under either aerobic or hypoxic conditions. In contrast, the 4- and 6-electron reduction products, 1-methyl-2-[hydroxylamino]imidazole and 1-methyl-2 aminoimidazole, respectively, failed to modify cell kill by L-PAM even at millimolar concentration. These results suggest that nitrosoimidazoles may be the active chemosensitizing species generated upon the reductive metabolism of nitroimidazoles. PMID- 2260991 TI - Evaluation of several oximes as reactivators of unaged soman-inhibited whole blood acetylcholinesterase in rabbits. AB - The antidotal benefit of oximes against organophosphorus (OP) anticholinesterase intoxication is thought to be due to reactivation of the OP-inhibited acetylcholinesterase (AChE). This study was conducted to determine whether the antidotal efficacy against soman by the oximes 2-hydroxyiminomethyl-3-methyl-1-[2 (3-methyl-3-nitrobutyl oxymethyl)]-imidazolium Cl (ICD 467) and 1,1' methylenebis[4-(hydroxyiminomethyl) pyridinium] di-Cl (MMB-4) resulted, in part, from reactivation of the inhibited AChE. These oximes were tested in parallel with pralidoxime Cl (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridinio-3-(4 carbamoyl-1-pyridinio+ ++)-2-oxapropane di-Cl (HI-6). Rabbits were atropinized (8 mg/kg, i.m.) and intoxicated with soman (13 micrograms/kg, i.v.; 1.2 x LD50) 5 min later. Three minutes after soman, animals were treated with oxime (50, 100 or 150 mumol/kg, i.m.). Whole blood was collected from a catheter in the central artery of the ear just before soman, at 2 min after soman and at 2, 5, 10, 15, 30, and 60 min after oxime or vehicle for determination of AChE activity. Shortly thereafter, animals were anesthetized and exsanguinated with immediate flushing using heparinized saline. AChE activity was also determined on the cortex, medulla-pons and diaphragm to assess central and peripheral reactivation. Treatment with HI-6 or MMB-4 (50 mumol/kg, i.m.) resulted in significant (P less than 0.05) reactivation of soman-inhibited whole blood AChE and diaphragm cholinesterase (ChE), but not brain AChE. In contrast, 2-PAM was completely ineffective in reactivating soman-inhibited AChE. HI-6 was significantly better than MMB-4 in reactivating blood AChE; they were essentially equal against soman inhibited diaphragm ChE. Three animals exposed to soman and treated with ICD 467 died within 15 min. When animals not exposed to soman were treated with ICD 467 (25 mumol/kg, i.m.), whole blood AChE activity was depressed by 60% within 5-10 min after treatment. Furthermore, ICD 467 failed to reactivate significantly unaged soman-inhibited erythrocyte AChE, in vitro. These observations indicate that ICD 467 would be contraindicated as a therapy for anti-ChE intoxication and that the efficacy of HI-6 or MMB-4 can be explained, in part, by reactivation of soman-inhibited AChE. PMID- 2260992 TI - Effects of granulocyte-macrophage colony-stimulating factor on 3'-azido-3' deoxythymidine uptake, phosphorylation and nucleotide retention in human U-937 cells. AB - Previous studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) both increases and decreases levels of 3'-azido-3'-deoxythymidine (AZT) nucleotides in certain human myeloid cells. The present studies have examined the effects of GM-CSF on AZT metabolism in U-937 cells. The results demonstrate that GM-CSF stimulated AZT nucleotide formation in these cells. This stimulation was detectable during concurrent exposure to GM-CSF and AZT or as a result of pretreatment with GM-CSF. The GM-CSF-induced enhancement in AZT nucleotide formation was associated with a 4-fold increase in AZT uptake. The finding that uptake of AZT into U-937 cells was only partially sensitive to 6-[(4 nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) suggested a process primarily involving nonfacilitated diffusion. The results also demonstrate that treatment of U-937 cells with GM-CSF was associated with nearly a 2-fold increase in thymidine kinase activity. Moreover, the findings indicate that retention of AZT-MP and AZP-TP was prolonged significantly (P less than 0.05 and P less than 0.01 respectively) in association with GM-CSF treatment. Taken together, these results suggest that GM-CSF enhances the formation of AZT nucleotides by increasing AZT uptake and phosphorylation, as well as increasing retention of phosphorylated derivatives. PMID- 2260993 TI - Pharmacological inhibition of forskolin-stimulated adenylate cyclase activity in rat brain by melatonin, its analogs, and diazepam. AB - Preincubation of rat forebrain membranes for 30-60 min with micromolar concentrations of the pineal hormone, melatonin, significantly inhibited forskolin-stimulated adenylate cyclase (AC) activity. Melatonin had an EC25 (concentration which inhibited AC activity by 25%) of 600 microM and caused a maximal inhibitory effect of approximately 30% at a concentration of 1000 microM. A comparison of the effects of melatonin and its analogs, 6-chloromelatonin and 2 iodomelatonin, in the striatum revealed that these halogenated drugs were 2-3 times more potent than melatonin in inhibiting AC activity. The EC25 values were 611, 226 and 189 microM for melatonin, 6-chloromelatonin and 2-iodomelatonin respectively. The receptor antagonists phentolamine (alpha-adrenergic), propranolol (beta-adrenergic), and metergoline (serotonergic) did not block the effect of melatonin in forebrain membranes. The central-type benzodiazepine (BZ) antagonist, Ro 15-1788 (flumazenil), also failed to block the inhibitory effects of melatonin, and the benzodiazepines, diazepam and Ro 5-4864, on AC activity. Evidence that inhibition of adenylate cyclase activity may be involved in the prevention of seizures suggests that the reported anticonvulsant effect of large doses of melatonin may be due to this mechanism. The greater potency of the halogenated melatonin analogs in inhibiting AC suggests that further study of their potential usefulness as anticonvulsants would be worthwhile. PMID- 2260994 TI - Endothelin-1 and platelet activating factor stimulate thromboxane A2 biosynthesis in rat vascular smooth muscle cells. AB - The effect of endothelin-1 (ET-1) on the release of thromboxane A2 (TXA2) was examined in cultured rat vascular smooth muscle cells (VSMC). ET-1 (10(-11) to 10(-6) M) significantly stimulated the release of thromboxane B2 (TXB2), a stable metabolite of TXA2. These effects of ET-1 were blocked by a cyclooxygenase inhibitor (indomethacin), a TXA2 synthetase inhibitor (CV-1451) and a specific platelet activating factor (PAF) antagonist (CV-6209). Additionally, PAF (10(-11) to 10(-6) M) stimulated the TXB2 release. Pretreatment with the phospholipase A2 inhibitor dexamethasone potently inhibited both ET-1 and PAF-induced elevation of cytosolic free Ca2+ concentrations [( Ca2+]i) in fura-2-loaded VSMC. These results clearly demonstrate that both ET-1 and PAF stimulate TXA2 biosynthesis in cultured rat VSMC, and TXA2 may contribute to the elevation of [Ca2+]i induced by ET-1 or PAF in VSMC. Furthermore, the stimulation of TXA2 biosynthesis may be a result of PLA2 activation by not only ET-1 but also PAF. PMID- 2260995 TI - On the mechanism of induction of microsomal cytochrome P450IVA1 and peroxisome proliferation in rat liver by clofibrate. AB - The time course of induction of microsomal and peroxisomal lipid-metabolizing enzymes in male Wistar rat liver has been investigated following a single i.p. dose of clofibrate (250 mg/kg). The microsomal enzyme, cytochrome P450IVA1, demonstrated a biphasic response to sodium clofibrate administration, the biphasic response consisting of an initial small response, peaking at approximately 30 min post-dose and returning to near baseline values after 2 hr. A second major induction of cytochrome P450IVA1 occurred between 18 and 24 hr post-dose. This biphasic phenomenon for cytochrome P450IVA1 was observed for the enzyme activity (lauric acid hydroxylase), immunodetectable protein (using a specific ELISA method) and at the mRNA level (using a 2.1 kilobase cytochrome P450IVA1 cDNA probe). In contrast, peroxisomal fatty acid beta-oxidation enzymes responded in a monophasic manner to clofibrate administration, peaking approximately 24 hr post-dose. Accordingly, microsomal cytochrome P450IVA1 was induced before the peroxisomal enzymes of fatty acid beta-oxidation. The effect of cycloheximide on the induction of peroxisome proliferation by clofibrate was additionally investigated. The prior administration of cycloheximide to Wistar rats ablated the clofibrate-dependent induction of both cytochrome P450IVA1 and peroxisomal-dependent lipid metabolism and also blocked the corresponding synthesis of enzyme proteins. Cycloheximide additionally inhibited the clofibrate dependent increase in peroxisomal acyl-CoA oxidase mRNA, but was without effect on the induced cytochrome P450IVA1 mRNA levels, indicating a protein or enzyme dependency for the phenomenon of peroxisome proliferation. Taken collectively, our data strongly argues that the regulation of microsomal cytochrome P450IVA1 and peroxisomal fatty acid beta-oxidation enzymes are closely related, possibly through the initial, clofibrate-dependent regulation of cytochrome P450IVA1. PMID- 2260996 TI - Inhibition by cyclosporin A and butylated hydroxytoluene of the inner mitochondrial membrane permeability transition induced by adriamycin aglycones. PMID- 2260997 TI - Clinical and pathologic studies of twenty-six patients with penetrating foreign body injury to the joints, bursae, and tendon sheaths. AB - Foreign body synovitis has been neglected in the rheumatology literature. We describe 26 patients in whom arthritis, bursitis, or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body. Twenty-two patients presented with acute synovitis, which was followed by chronic or recurrent inflammation mimicking septic arthritis, osteomyelitis, monarticular juvenile rheumatoid arthritis, bone tumor, or apatite deposition disease. Foreign bodies were not seen in 5 inflammatory synovial fluids studied, but were seen in the synovium or periarticular tissues of 17 patients. Excisional biopsy was required in most patients for precise diagnosis and treatment. PMID- 2260998 TI - Magnetic resonance imaging of sacroiliac joint inflammation. AB - A consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The diagnostic sensitivity of MRI was similar to that of computed tomography or conventional radiography. However, MRI seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow. The results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints. PMID- 2260999 TI - Pregnancy and the risk of developing rheumatoid arthritis. AB - There have been conflicting reports on, and no plausible biologic explanation for, a protective effect of oral contraceptive (OC) use on the development of rheumatoid arthritis (RA). Therefore, we investigated aspects of behavior related to OC use that could explain the preventive effect of OC on the onset of RA. In the present case-control study, past pregnancy, age at first pregnancy, and pregnancies with adverse outcome were studied as possible risk factors for RA. Interview information on reproductive variables was obtained from 135 young adult women with confirmed definite or classic RA of recent onset, and from 378 control patients with soft tissue rheumatic disorders or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. We found a decreased risk of RA in women who had been pregnant. The risk of RA in women who had ever been pregnant compared with women who had never been pregnant was 0.49 (95% confidence interval 0.27-0.91). The earlier the first pregnancy, the lower the risk of RA. Pregnancy with adverse outcome (i.e., gestation less than 25 weeks) did not substantially change the risk of RA (relative risk 0.73, 95% confidence interval 0.50-1.07). The protective effect of pregnancy was independent of OC use, the presence of HLA-DR4, or a family history of RA. Immune modulation by female hormonal influences could be an explanation for the results of the present study. PMID- 2261000 TI - HLA antigens in juvenile arthritis. Pauciarticular and polyarticular juvenile arthritis are immunogenetically distinct. AB - Using DNA techniques, we investigated the role of HLA-DR, DQ, and DP alleles in susceptibility to juvenile arthritis (JA). We studied 2 groups of patients with JA having a different disease prognosis and course. The pauciarticular form is usually benign, while the polyarticular disease frequently leads to joint destruction and disability. Persistent pauciarticular disease developed preferentially in patients having HLA-DRw13-Dw18 and DQw6-Dw18, but these antigens did not confer susceptibility in patients whose disease converted to the polyarticular form. HLA-DPw2.1 was an additional susceptibility factor for patients with JA of pauciarticular onset. In the polyarticular form of JA, HLA DPw3 was the major factor for susceptibility, giving a relative risk of 10.3 (P less than 0.0001). In addition, we found that DRw8.1 and DQw4 were increased, and HLA-DR4 was markedly decreased, in patients with pauciarticular and polyarticular disease. These results indicate that in addition to some shared factors, distinct HLA class II alleles are important in pauciarticular or polyarticular JA. We conclude that typing with oligonucleotide probes may be useful in predicting the outcome in some children with arthritis. PMID- 2261001 TI - Yersinia enterocolitica in the synovial membrane of patients with Yersinia induced arthritis. AB - Using a monospecific rabbit antibody against Yersinia enterocolitica outer membrane protein 1, we examined synovial biopsy specimens from 7 patients with Yersinia-induced arthritis. Yersinia were demonstrated in the synovial membrane by indirect immunofluorescence in 4 patients with Yersinia-induced arthritis, but not in 6 control patients with Salmonella-induced arthritis or with rheumatoid arthritis. These findings suggest the persistence of Yersinia in the joints of patients with Yersinia-induced arthritis. PMID- 2261002 TI - Catabolic effects of muramyl dipeptide on rabbit chondrocytes. AB - Muramyl dipeptide, an essential structure for the diverse biologic activities of bacterial cell wall peptidoglycan, inhibited the synthesis of glycosaminoglycan/proteoglycan in cultured rabbit costal chondrocytes in a dose dependent manner. Muramyl dipeptide, as well as lipopolysaccharide and interleukin-1 alpha, also enhanced the release of 35S-sulfate-prelabeled glycosaminoglycan/proteoglycan from the cell layer, which seems to reflect, at least partially, the increasing degradation of glycosaminoglycan/proteoglycan. Five synthetic analogs of muramyl dipeptide known to be adjuvant active or adjuvant inactive were tested for their potential to inhibit synthesis of glycosaminoglycan/proteoglycan and to enhance the release of glycosaminoglycan/proteoglycan in chondrocytes. The structural dependence of these synthetic analogs on chondrocytes was found to parallel that of immunoadjuvant activity. These results suggest that muramyl dipeptide is a potent mediator of catabolism in chondrocytes. PMID- 2261003 TI - Increased expression of type VI collagen genes in systemic sclerosis. AB - The expression of type VI collagen genes in affected skin from patients with systemic sclerosis (SSc) was examined by in situ hybridizations with a human alpha 2(VI) collagen sequence-specific complementary DNA. Five patients with diffuse, rapidly progressive SSc of recent onset (less than 12 months) were studied. The results showed increased expression of alpha 2(VI) collagen messenger RNA transcripts in the skin of scleroderma patients compared with that in the skin of normal subjects. These findings indicate that alterations in the expression of type VI collagen genes, similar to those previously described for types I and III collagen, are present in the affected skin of SSc patients. These alterations may result in excessive tissue accumulation of type VI collagen and may play a role in the progressive skin induration and sclerosis that are prominent features of SSc. PMID- 2261004 TI - Antihistone antibodies in antinuclear antibody-positive juvenile arthritis. AB - The binding of antinuclear antibody-positive juvenile arthritis (JA) sera to bovine thymus histones H1, H2A, H2B, H3, and H4 was studied by an enzyme-linked immunosorbent assay. Seventy-five percent of the JA patients tested positive for at least 1 antibody specificity. Antihistone antibodies were predominantly IgM, while IgG antibodies were less common and were restricted to histones H1 or H3. In the group of patients with JA of pauciarticular onset, antihistone antibodies were significantly more elevated in patients with past or present uveitis than in patients without a history of uveitis. Anti-H1 antibodies in JA patients were found to react mostly with determinants located in the carboxyl-terminal domain of the H1 molecule. Sera were also reactive with human histone H1(0) or chicken histone H5, which are H1 variants found only in nondividing cells. PMID- 2261005 TI - Adrenal insufficiency in two women with anticardiolipin antibodies. Cause and effect? AB - We describe 2 women with anticardiolipin antibodies and a lupus-like disorder who developed acute adrenal insufficiency. We also review 5 similar cases reported previously. Anticardiolipin antibodies appear to be a risk factor for this vascular complication. PMID- 2261006 TI - Cutaneous vasculitis associated with pheochromocytoma. AB - We describe a patient who presented with constitutional symptoms, severe hypertension, and purpuric lesions over the knees, thighs, and penis. The patient was eventually diagnosed as having multiple endocrine neoplasia type II, with cutaneous leukocytoclastic vasculitis. The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids, but rapidly resolved after the removal of bilateral pheochromocytomas. This case demonstrates cutaneous leukocytoclastic vasculitis in association with pheochromocytoma. PMID- 2261007 TI - Comment on the 1990 American College of rheumatology criteria for fibromyalgia. PMID- 2261008 TI - Granulocyte-macrophage colony-stimulating factor treatment of neutropenia associated with Felty's syndrome. PMID- 2261009 TI - Antibody to a specific HLA-DR beta 1 sequence in Japanese patients with rheumatoid arthritis. PMID- 2261010 TI - Unsuccessful search for mutant fibronectin genes in patients with systemic sclerosis. PMID- 2261011 TI - Multicentric reticulohistiocytosis and Sjogren's syndrome. PMID- 2261012 TI - Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice. AB - We have previously demonstrated a dramatic preference for utilization of the most JH-proximal VH gene segments in the newborn liver versus adult spleen. We now examine in detail the relative expression of different VH gene families throughout ontogeny and in immunodeficient mice to gain insight into factors that cause the shift in VH usage. We find that the relative expression of VH gene families remains constant and biased throughout fetal and neonatal liver development. In addition, the primary VH repertoire expressed in neonatal spleen displays a similarly biased, position-dependent VH repertoire. The pattern of VH gene expression begins to change at 5-7 d postnatally and reaches the adult randomized pattern at approximately 2 wk of age. We also find biased expression of JH-proximal VH gene families in adult bone marrow and in spleens of adult leaky scid mice, suggesting that the spontaneously generated repertoire of adult mice is similar to that observed in neonates. Together, these data suggest that a position-dependent repertoire is generated in differentiating pre-B cells at all stages of ontogeny, at least in part, as a result of preferential rearrangement of proximal VH gene segments. Therefore, mechanisms subsequent to V gene rearrangement, such as regulatory interactions and antigen selection, must play a major role in normalizing the repertoire. PMID- 2261013 TI - Synthesis of human coagulation factor XIII in yeast. AB - The active form of coagulation factor XIII, factor XIIIa, is a transglutaminase that covalently cross-links fibrin molecules by joining gamma-glutamyl and epsilon-lysyl primary amino groups. In this paper we report the design of a yeast expression vector called pPH3 which includes the GAL1-GAL10 promoter, multiple cloning sites, the URA3 selectable marker, the 2 mu sequences and the ampicillin resistance gene. We have placed full-length factor XIII cDNA into the PstI site of this vector, transformed the yeast cells and expressed human coagulation factor XIII which was found to be enzymatically active based on observations that this recombinant factor XIII: (a) showed immunological identity with placental factor XIII; (b) was demonstrated to have transglutaminase activity, and (c) cross-linked fibrin in a manner identical to human placental factor XIIIa catalyzed polymerization (gamma-gamma dimerization and alpha polymerization). PMID- 2261014 TI - Specific bradycardic agents. 1. Chemistry, pharmacology, and structure-activity relationships of substituted benzazepinones, a-new class of compounds exerting antiischemic properties. AB - Structural modification of the calcium-antagonist verapamil (1) by replacement of the lipophilic alpha-isopropylacetonitrile moiety by various heterocyclic ring systems has led to a new class of cardiovascular compounds which are characterized by a specific bradycardic activity. These agents reduce heart rate without binding to classical calcium channels or beta-adrenoceptors, interacting instead specifically with structures at the sino atrial node. Therefore they have also been termed sinus node inhibitors. The prototype falipamil (2) has been submitted to further optimization mainly by manipulation of the phthalmidine moiety. This has resulted in a second generation of specific bradycardic agents with increased potency and selectively and prolonged duration of action represented by the benzazepinone-derivative UL-FS 49 (4). Structure-activity relationships within this novel class of compounds have revealed a marked dependence of activity on the substitution pattern of the aromatic rings, the nature of the central nitrogen atom, and the length of the connecting alkyl chains. The crucial role of the benzazepinone ring for bradycardic activity can be best explained by its special impact on the overall molecular conformation. PMID- 2261015 TI - Treatment of psoriasis with triamcinolone acetonide 0.1% under occlusion: a comparison of two hydrocolloid dressings. AB - A clinical, randomized, parallel study was undertaken to compare the efficacy of a widely known steroid preparation, triamcinolone acetonide 0.1% cream, in occlusion with two different hydrocolloid dressings, namely Duoderm and Actiderm, in the treatment of chronic plaques of psoriasis. A total of 23 patients with psoriasis were entered in the study. Two similar psoriatic plaques were identified in each patient, triamcinolone acetonide cream was applied, and a randomized table assigned the sides of the body to which each dressing was to be used for each patient. Changing of the dressing, with reapplication of the cream was done every 48 hours on each side until the lesions cleared or for a maximum of three weeks. At the end of the three weeks-therapy, period, 12 lesions had totally cleared with Duoderm and 13 with Actiderm. Seven lesions had achieved either marked or moderate improvement with duoderm and the same results were observed with Actiderm. Only three of 22 had mild improvement with Duoderm and two of 22 with Actiderm. No side effect were noted and none of the patients became worse during this treatment. This study demonstrated the beneficial effects of triamcinolone acetonide 0.1% cream under occlusion with two different hydrocolloid dressings in the treatment of chronic resistant plaques of psoriasis. The use of a hydrocolloid dressing in combination with steroid adds another therapeutic option for the treatment of chronic localized psoriatic lesions. PMID- 2261016 TI - Left ventricular assistance with the centrifugal pump: management of the patient with stunned myocardium. AB - Prompt left ventricular assistance by the centrifugal pump enables the survival of many patients with postoperative low cardiac output who cannot be weaned from cardiopulmonary bypass with the aid of balloon counterpulsation and inotropic agents. Successful weaning from the centrifugal pump, however, depends on the careful selection of appropriate candidates as well as the strict control of pump flow, oncotic pressure, coagulopathy, blood pressure, and systemic afterload. The installation of a hemoconcentration device into the pump line helps control hemodilution and maintain adequate oncotic pressure. The management of a patient who was totally dependent upon left ventricular assistance is described. PMID- 2261017 TI - Initial evaluation of the asthmatic patient. AB - Bronchial asthma is a common disease that is not yet completely understood. We specify the basic evaluation that asthmatic patients should undergo and discuss some aspects of pathophysiology. Guidelines to select patients for further evaluation are suggested. PMID- 2261018 TI - [Infant colic]. AB - The literature regarding infantile colic is reviewed. It is characterized by difficulties in definition. Different theories have been implied as to its etiology: behavioral and developmental as well as gastrointestinal causes are considered. The management and treatment based on both theories were revised. Most of them have proven to be effective in many cases. We recognize that future research is needed so that better management and treatment can be designed and prepared for this condition. PMID- 2261019 TI - Diabetic's diet in the Hispanic Caribbean. PMID- 2261020 TI - Truncated opportunities no-place for serendipity. PMID- 2261021 TI - [Pre-conception care]. PMID- 2261022 TI - [A good service organized for control of acute and chronic pain: why can't we get one in Puerto Rico?]. PMID- 2261023 TI - Albinism and Hermansky-Pudlak syndrome in Puerto Rico. AB - Five types of oculocutaneous albinism and two types of ocular albinism were found among 349 Puerto Rican albinos. The most prevalent type of albinism was the Hermansky-Pudlak syndrome (HPS). HPS was observed in five of every six albinos in Puerto Rico. The prevalence of HPS was highest in the northwestern quarter of the island, affecting approximately one in 1,800 persons, and approximately one in 22 are carriers of the gene. HPS is an autosomal recessively inherited triad of a tyrosinase-positive type of albinism, a hemorrhagic diathesis due to storage pool deficient platelets and accumulation of ceroid in tissues. The pigmentary phenotype of HPS albinos resembled that of any other type of oculocutaneous or ocular albinism. The most reliable method of diagnosing HPS is by a deficiency of platelet dense bodies observed by electron microscopy. The accumulation of ceroid in the tissues is associated with fibrotic restrictive lung disease and granulomatous enteropathic disease. The enteropathic disorder resembles Crohn's disease and with few exceptions, had its onset after 13 years of age. The major causes of death were fibrotic restrictive pulmonary disease, hemorrhagic episodes and sequelae of granulomatous enteropathic disease. Menometrorrhagia was common in women with HPS. No immune deficiency was found in HPS patients. The majority of patients with HPS had visual acuities of 20/200 or worse and consequently were legally blind. Albinos of all types, including HPS, lacked binocular vision due to nearly complete crossing of the optic tracts. PMID- 2261024 TI - Primary lateral sclerosis: a distinct clinical entity in patients with chronic spastic paraparesis. AB - The development of neurologic deficits confined to the corticospinal tracts has been referred as Primary Lateral Sclerosis (PLS). Through the years, this diagnosis has remained uncertain. In this study we describe seven patients with chronic involvement of the pyramidal system. Two of these patients had serologic evidence of human T-lymphotrophic virus type I infection, one patient had multiple sclerosis and in four patients the clinical diagnosis of PLS was made. The clinical characteristics and diagnostic studies of these patients are presented. A review of the literature with emphasis in the differential diagnosis and a proposed workup for patients with chronic spastic paraparesis are made. This study provides supporting evidence in favor of the clinical entity of PLS. PMID- 2261025 TI - Misreporting of maternal mortality in Puerto Rico. AB - Maternal mortality (MM) continues to be a problem that plagues many developed and underdeveloped countries around the world. It has been estimated that the minimum amount of underreporting in the U.S. to be 20%, resulting in MM rates that may be substantially higher than reported. The national goal for the MM for the year 1990 has been set at 5/100,000, and at the present trend it is expected that this may be achieved among the white population, but not among minorities. P.R. reported a maternal mortality rate of 5/100,000 in 1975. It was suspected that such a low rate was due to underreporting, a study was undertaken to investigate that possibility. The results indicated that there was severe underreporting of maternal deaths during 1978 = 79. Recently, there has been a growing concern that the level of underreporting in PR continues to be high. Since there has been no evidence that the surveillance has improved, the Dept. of Health requested from the Dept. of Ob-Gyn of the University of Puerto Rico Medical School and the Dept. of Maternal and Child Health to conduct a study to find out if the previous findings held true for recent years. The study was based on the review of selected medical records corresponding to deaths of women of childbearing age whose causes of death, as coded in the death certificate, were considered as having a high probability of masking a misreported maternal death. It was decided to investigate those deaths occurring in 1982, to see if the results of the previous study had caused any impact on the surveillance of maternal deaths in Puerto Rico. PMID- 2261026 TI - [Morphofunctional profile of Puerto Rican gymnasts]. AB - This study described the body composition, somatotype, physiological maturity, flexibility and cardiorespiratory endurance of 30 gymnasts (feminine; n = 12 and masculine; n = 18) pre selected for the puertorican national team and compared the results with those reported in the literature. There were significant differences between the sexes in body fat, lean body mass, ISA, CMB, AMB, endomorphy, mesomorphy, sum of skinfolds, flexibility and VO2max (L.min-1), (p less than .05). The results are within the range reported in the literature for elite gymnasts. PMID- 2261027 TI - [Adolescents and school health in the 90's]. PMID- 2261028 TI - Pseudomyxoma peritonei: case report and review of the literature. AB - Pseudomyxoma peritonei is a rare entity manifested by implants of a mucinous gelatinous material arising from either the appendix or ovary and involves the peritoneal cavity, peritoneum and omentum. Preoperative diagnosis is feasible by means of radiographic studies. The main step in the treatment is debulking surgery with appendectomy, bilateral oophorectomy and omentectomy. Adjuvant radiotherapy and chemotherapy has been used. Long term survival is around 54% at five years. Here we present a case of a ruptured mucocele of the appendix and pseudomyxoma who presents as massive increase in the abdominal girth of two years evolution. PMID- 2261029 TI - Spontaneous pneumomediastinum. AB - A 15-year-old pregnant girl developed severe substernal pain during the final effort to give birth to her first child. Shortly thereafter a growing crepitant suprasternal swelling was noted. Pneumomediastinum and subcutaneous emphysema was clearly demonstrated by a chest film showing mediastinal air dissecting towards the neck and supradiaphragmatically. The causes and physiopathology of spontaneous pneumomediastinum are reviewed. The therapeutic use of oxygen is discussed. PMID- 2261030 TI - [Service rationing at pediatric hospitals]. PMID- 2261031 TI - Nutrition and athletic performance. AB - Energy, CHO and possibly protein needs are higher for athletes than for typical persons. CHO supplementation during and after exercise is important for endurance athletes. A balanced diet, adequate in calories, can meet the vitamin and mineral needs of virtually all athletes. Athletes must be aware of maintaining an optimum hydration status. Intensive nutrition education efforts are needed to combat to combat quackery and fads that are targeted to athletes. PMID- 2261032 TI - A cognitive perspective on medical expertise: theory and implication. AB - A new theory of the development of expertise in medicine is outlined. Contrary to existing views, this theory assumes that expertise is not so much a matter of superior reasoning skills or in-depth knowledge of pathophysiological states as it is based on cognitive structures that describe the features of prototypical or even actual patients. These cognitive structures, referred to as "illness scripts," contain relatively little knowledge about pathophysiological causes of symptoms and complaints but a wealth of clinically relevant information about disease, its consequences, and the context under which illness develops. By contrast, intermediate-level students without clinical experience typically use pathophysiological, causal models of disease when solving problems. The authors review evidence supporting the theory and discuss its implications for the understanding of five phenomena extensively documented in the clinical-reasoning literature: (1) content specificity in diagnostic performance; (2) typical differences in data-gathering techniques between medical students and physicians; (3) difficulties involved in setting standards; (4) a decline in performance on certain measures of clinical reasoning with increasing expertise; and (5) a paradoxical association between errors and longer response times in visual diagnosis. PMID- 2261033 TI - Shifting paradigms of research in medical education. PMID- 2261034 TI - The interactive videodisc in healthcare. PMID- 2261035 TI - Developing videodisc instructions for health sciences: a consortium approach. PMID- 2261036 TI - Of codes and keywords: standards for biomedical nomenclature. PMID- 2261037 TI - National policy prospectives. Oregon's bold idea. PMID- 2261038 TI - National policy prospectives. Oregon's bold mistake. PMID- 2261039 TI - A national survey of grading systems used in medicine clerkships. AB - To better understand the variety in U.S. medicine clerkship grading terminology, the number of grading levels, and the distribution of grades within each level, the authors surveyed medicine clerkship directors in the United States and Puerto Rico in 1986 and 1987. Completed questionnaires were returned from 101 of the 124 medical schools (81%). Descriptor grades were the most commonly used form of grading of medicine clerks, used in 68 of the 101 responding schools; letter grades were used by another 28 of the schools; and four schools used a numerical grading system. Although descriptor grades were most commonly used for grading medicine clerks, there was lack of consistency in their use between schools. The authors discuss the data related to letter grades and descriptor grades across this representative sample of U.S. medical schools. PMID- 2261040 TI - Factors important to students in selecting a residency program. AB - A 22-item questionnaire, designed to assess the factors students considered important when they ranked residency programs, was distributed to the 1988 senior class of Tulane University School of Medicine just before the submission deadline of the National Residency Matching Program. Completed surveys were obtained from 111 of the 157 graduating students (approximately 71%) and were representative of the entire class in terms of sex, age, race, marital status, and anticipated field of specialization. Results of this investigation suggest that the satisfaction of a program's house officers and the seniors' general impression at the interview were the most important selection factors of the matriculating seniors surveyed. Diversity of the training experience and geographic location were also important selection factors. House officer benefits and salary were low priority factors in the seniors' program selections. PMID- 2261041 TI - Pediatrics residents' attitudes about insulin-dependent diabetes mellitus and children with diabetes. AB - Nationwide, pediatricians provide a substantial portion of the health care of children with diabetes. Their beliefs and attitudes about diabetes and children with the illness have an important influence on their treatment decisions. The attitudes and beliefs of a 1988 sample of pediatrics residents were compared with data from a 1987 national survey of practicing pediatricians' beliefs and attitudes about children with insulin-dependent diabetes mellitus and about the disease itself. Pediatrics residents in their second and third years of training were considerably more negative about diabetes and diabetic children than were either the members of the national sample of practicing pediatricians or the residents' first-year colleagues. PMID- 2261042 TI - Reactions of first-year medical students to their initial encounter with a cadaver in the dissecting room. AB - This study reports the results of a 1986 questionnaire survey of 100 first-year medical students regarding their preparation for and reactions to their first encounter with a human cadaver in the dissecting room. The students were aware of psychological and physical reactions to this experience, and although they felt adequately prepared prior to the class, expressed a desire for greater preparation afterwards, particularly through more discussion of the experience with the anatomy staff. A surprising number of the students (62) had had prior exposure to a dead human body, which was a significant influence upon their reactions. The results of this study suggest a need for improving both the preparation for coping with dissection and the follow-up opportunities for dealing with professional and emotional issues raised during human dissection. PMID- 2261043 TI - An attempt to motivate internal medicine housestaff to obtain consent for autopsies. AB - The impact that a 50-minute lecture on the value of the autopsy had on the subsequent obtaining of autopsies by housestaff training in internal medicine at a teaching hospital was examined in a prospective one-year clinical trial from mid-1987 to mid-1988. The group that attended the lecture (n = 27) did not subsequently obtain a greater mean number or frequency of permissions for autopsies than did the control group (n = 26), whose members did not attend, and did not indicate more frequently in the patients' charts that autopsies had been sought. In addition, in the total group of 53 housestaff, five (9.4%) did not write a pronunciation-of-death entry, and 26 (49%) did not obtain permission for a single autopsy during the study period. Future efforts to enhance the appreciation for the autopsy among physicians in training may need to use more sophisticated techniques than a lecture in order to increase housestaff motivation to obtain consent for autopsies. PMID- 2261044 TI - A comparison of the emphasis given to nine therapies in residency training and later practice of psychiatrists. AB - This study compared the emphasis given to various therapies in six psychiatry residencies and by psychiatrists in their later practice. Eighty-seven psychiatrists and 29 residents were surveyed in 1987. The two groups reported that almost the same amounts of time of their respective training programs had been devoted to the nine therapies surveyed. Patterns of practice were observed, including the finding that those who were highly trained in a therapy practiced it more than did those who had less training. Both those who were highly trained and those who were not extended their practices to the use of therapies in which their training was not extensive. Problems in the study design and variables affecting this type of research are identified as guidance for future investigations. PMID- 2261045 TI - Scientific writing courses for pediatrics fellows. AB - A six-week course in scientific writing and publishing was developed for pediatrics fellows at the University of Florida College of Medicine in 1984. It covered three areas: (1) grammar, syntax, and prose style; (2) construction of scientific papers; and (3) the submissions and review process. Increasing enrollment and the requests of course graduates led to the development of a second course, Advanced Scientific Writing; both courses are now offered annually. Class materials consist of texts in scientific writing, comprehensive syllabi, and handouts; the focus is on workshop activities, exercises, collaboration with peers, and individual consultations with the instructor. At the end of each course, participants complete detailed evaluation instruments, and the data obtained are used to modify the course's structure and content the following year. PMID- 2261046 TI - Using a sociomatrix to evaluate the effectiveness of small-group teaching to residents. AB - This article describes a 1988 pilot study in a family medicine residency program of the use of a sociomatrix to assess small-group teaching. A multidisciplinary team developed a sociomatrix coding sheet, which was used by a family physician psychiatrist to classify behaviors seen on videotaped small-group teaching sessions, which were held at the conclusion of patient care activities. Although the sociomatrix appears to have the potential to relate specific leader behaviors to residents' feedback regarding subjective learning outcomes, the number of observations was too small to permit clear conclusions regarding optimal teaching behaviors and styles. PMID- 2261047 TI - The procedural skills of medical students: expectations and experiences. AB - The procedural skills that medical students should learn were identified by a survey of faculty and residents at the University of North Carolina at Chapel Hill School of Medicine in 1985. Those who responded indicated that it was important for students to have exposure to all 52 procedures listed on the questionnaire. Only a small number of procedures were identified by 75% or more of those who responded as being important for students to perform with proficiency (11 procedures identified by the faculty, nine by the residents). On another questionnaire, the graduating medical students indicated that, for the most part, they had experience performing these important procedures. To ensure clinical competency, expectations regarding these skills should be communicated to students, faculty, and residents and, ideally, a system should be established to assess these skills. PMID- 2261048 TI - Evaluating a seminar designed to improve psychiatry skills of family medicine residents. AB - In an effort to evaluate the effectiveness of a psychiatry seminar designed to teach the principles of psychiatric history taking, diagnosis, and management to first-year family medicine residents, an Objective Structured Clinical Examination (OSCE) and accompanying marking system were designed and used in 1988. The OSCE scores of the family medicine residents who had participated in the psychiatry seminar were significantly higher than the scores of the first year family medicine residents who had not. The author concludes that this educational format can be effective in teaching psychiatric diagnostic and management skills to first-year family medicine residents, and that further research is necessary to validate the effectiveness of current educational models. PMID- 2261049 TI - The presence of student-based peer advising, peer tutoring, and performance evaluation programs among U.S. medical schools. PMID- 2261050 TI - Hand function in selection of orthopedics residents. PMID- 2261051 TI - Identifying personnel to receive continuing medical education about appropriate use of blood transfusions. PMID- 2261052 TI - A medical problem-solving project for first-year medical students. PMID- 2261053 TI - Applying problem-based learning theory to the clinical clerkship. PMID- 2261054 TI - [Bacterial regrowth in drinking water. IV. Bacterial flora in fresh and stagnant water in drinking water purification and in the drinking water distribution system]. AB - Six dead end water pipes were installed inside a Zurich drinking water plant and five others over a distance of 12 km along the distribution system and the water was left stagnating in there for 2 weeks. A total of 1508 bacteria from fresh and stagnating water were isolated and identified. Of these, 241 bacterial isolates from the distribution system were examined using the nutrient-tolerance test, i.e. testing the ability to grow in tap water and in media with low and very high nutrient content. In the fresh water of the treatment plant specific bacterial populations were obtained, these occurring particularly after the filters. According to different chlorine dosage and chlorine demand, they were finally washed into the distribution system in varying amounts and compositions. It was shown that in the fresh water of the distribution system the genera of Pseudomonas, Azotobacter and Actinobacteria were each present at a level of approximately 30%. After two weeks stagnation non-fluorescing pseudomonads were dominating in the treatment plant as well as in the fresh water of the distribution system. All isolated Actinobacteria and Azotobacter and almost half of the Pseudomonads proved to be oligotrophic oligocarbotolerants or oligocarbophilic organisms in the nutrient-tolerance test. The other half of the Pseudomonads plus the Flexibacter species were mesotrophic oligocarbotolerants, since they could grow in tap water and in culture media with very high nutrient content. Attention is drawn to the unrecognized danger of recontamination of mesotrophic bacteria growing rapidly in stagnating drinking water, which is used as rinsing water for cleaning food processing equipment. PMID- 2261055 TI - The presence of Aeromonas in drinking water supplies in The Netherlands. AB - The occurrence of Aeromonas in raw, treated and distributed waters of 20 different treatment stations in the Netherlands was studied over a one-and-a-half year period. River water yielded highest numbers (greater than 10,000 cfu/100 ml) of predominantly anaerogenic strains. In open storage reservoirs for river water or dune infiltrate, numbers were usually between 1,000 and 10,000/100 ml with a majority of aerogenic strains, in particular A. sobria. River water after dune infiltration or pure dune water, collected in closed systems, as well as aerobic or anaerobic groundwater, were usually free of Aeromonas in 100 ml. Treated waters showed low counts (usually less than 10 cfu/100 ml), irrespective of raw water source. Regrowth of aeromonads occurred in 16 out of 20 distribution systems examined. Geometric means counts (2nd half of 1986) in these systems varied between 1 and 440 cfu/100 ml and maximum counts between 10 and 3300 cfu/100 ml. Aeromonas-densities were related to temperature and residence time, but not to total organic matter or heterotrophic plate counts. Regrowth occurred particularly in drinking water derived from anaerobic groundwater containing methane. A. hydrophila was the most frequently isolated species from distribution waters, but A. caviae and A. sobria were predominant in a few systems. PMID- 2261056 TI - [Characteristics of a new bioindicator and its testing in practice assays of thermal disinfection methods]. AB - Thermolysin (EC 3.4.24.4) is a thermostable metalloproteinase isolated from Bacillus thermoproteolyticus. It has been tested for its suitability as a macromolecular bioindicator for the screening of thermal disinfection methods. Using the time- und temperature-dependent inactivation rate of the immobilized enzyme we get a measure if given parameters of disinfection have been maintained. In order to determine standard conditions of practical use, physico-chemical properties of the enzyme (pH- and temperature-optimum, Km, Vmax) were ascertained first. Then, thermal inactivation of thermolysin was analyzed for temperatures between 75 degrees and 93 degrees C and exposition time 3-20 min. This new method of testing thermal disinfection is compared with conventional physical and microbiological testing methods; in addition values of reference for selected disinfection programs were analyzed. The bioindicator proved to be stable for up to 12 weeks of storage (room temperature). PMID- 2261057 TI - [Protective effect of thiocyanate in the model of the septic infected mouse]. AB - On the model of the septic mouse infected with mice pathogenic Erysipelothrix strain NaSCN had a protective effect (lower and delayed lethality in the doses of 64 and 256 mg/kg, given once a day intraperitoneally prophylactically or simultaneously to the infection. PMID- 2261058 TI - [Volatile organic halogen compounds in food]. AB - Volatile halocarbons have been found in raw water, chlorinated tap water, in blood of healthy individuals and patients, in milk, urine, solutions and laboratory suspensions manufactured by the Medical Industry. Tap water is also used in the food industry and therefore it is reasonable that they also could be analysed in food. PMID- 2261059 TI - [Dose-response pattern of inhaled sulfur dioxide (SO2) in rabbits pretreated with papain or sodium chloride aerosols]. AB - The study was conducted on 29 New-Zealand female rabbits to examine the dose response pattern of SO2 in inhaled air. A group of 14 animals was exposed to papain-aerosol (P-A) twice a week for 1 h each over 12 weeks in order to increase bronchial reactivity. A group of 9 animals received similar treatment but with saline-aerosol (NaCl-A); this group served for control. The third group of 6 animals remained untreated (K). After 12 weeks of treatment individual animals were anesthetized and the P-A and NaCl-A groups were exposed for 5 min each to different concentrations of SO2 (0.0, 1.0, 2.0, 4.0 and 9.0 mg/m3). The animals of group K were treated similarly but they were exposed 5X to synthetic air; this group served the purpose to follow the anesthesia effect on respiration and cardio-vascular system. The recovery period was 30 min between the exposures. The K-animals showed gradual decrease of lung resistance (R1). In contrast P-A and NaCl-A animals both showed a clear increase in R1 following exposure to SO2, and R1 was considerably higher in P-A than in NaCl-A animals. The maximum change in R1 was caused by exposure to 4.0 mg/m3 SO2 and it was even greater than the response produced by 9.0 mg/m3 SO2 in P-A animals. A similar pattern of response was also observed in NaCl-A animals, but the highest increase in R1 was caused by exposure to 2.0 mg/m3 SO2. From these results it can be concluded that high concentration of SO2 could have a damaging effect on sensory receptors of the tracheobronchial system. PMID- 2261060 TI - [The persistence of chemically different glass fibers in rat lungs]. AB - The half-times of glass fibre samples of different chemical composition and size was analysed in the rat lung. Up to two years after intratracheal instillation the number of fibres in the ashed lungs was determined by SEM. Half-times of fibre clearance of 40 to 240 days were calculated. PMID- 2261061 TI - Morphological heterogeneity among spirochetes isolated from cases of swine dysentery. AB - Pathogenic and non-pathogenic spirochetes isolated from the intestines of pigs were examined by electron microscopy using the negative staining and ultrathin sectioning techniques. Morphological differences were observed among cells of different strains. The cells differed in length as well as in width and in the number of flagella inserted at each end. In addition, the cells from different strains also varied in their resistance to the action of the detergents, Teepol and sodium deoxycholate. Three of the strains studied contained weakly haemolytic spirochetes, two of which differed markedly in their morphology from the cells of the other strains. These spirochetes had fewer flagella inserted at each end than those from other isolates and showed a distinct lattice-like substructure covering the ends of the cells. The spirochetes examined were found to be morphologically more similar to those of the genus Borrelia than to those of the genus Treponema but were clearly different from the cells of both of these genera. The taxonomic implications of the observations are discussed in brief. PMID- 2261062 TI - Applications of bacteriocin-like inhibitory substance (BLIS) typing in a longitudinal study of the oral carriage of beta-haemolytic streptococci by a group of Dunedin schoolchildren. AB - A longitudinal study of the distribution of oral beta-haemolytic streptococci in 103 children (ages 5-6 y) attending three Dunedin schools was initiated in February 1987. A total of 858 paired pharyngeal and saliva specimens were obtained in nine principal sampling sessions, the last being in May 1989. The detection rate of Lancefield group A streptococci in directly plated pharyngeal cultures (19.8%) was considerably higher than in the corresponding saliva cultures (5.1%). By contrast, Lancefield group F and serologically non-groupable beta-haemolytic Streptococcus anginosus tended to be more prevalent in saliva (10.9% positive) than in pharyngeal specimens (7.1%). Group A streptococci were recovered at least once from 59 (57.3%) of the subjects. Representative beta haemolytic streptococcus isolates were typed according to their production of bacteriocin-like inhibitory substances (BLIS) and by traditional serological techniques. The epidemiological value of BLIS typing was particularly evident in that both BLIS-positive and BLIS-negative strains could be differentiated within serotypes M1, M12 and M22 and also the serologically not typable group A streptococcus isolates. Ten children consistently had small numbers of group A streptococci present in their pharyngeal cultures, for periods of at least 12 months. In six of these subjects the carried strain was M-type 4/BLIS-type 655. This study has shown that in young schoolchildren long-term carriage of a variety of species of beta-haemolytic streptococci with little associated clinical evidence of infection may be common. PMID- 2261063 TI - Biological activities and endotoxic activities of protective antigens (PAgs) of Leptospira interrogans. AB - The biological and endotoxic activities of protective antigens (PAgs) prepared by the chloroform-methanol-water method from Leptospira interrogans serovars lai, copenhageni and canicola were examined. The PAg preparations did not show a local Shwartzman reaction in the rabbits at doses of 100 micrograms and 50 micrograms/site and lethal toxicity to galactosamine-sensitized mice at the dose of 12.5 micrograms to 50 micrograms/mouse. PAgs exhibited a weak cytotoxic action on peritoneal exudate macrophages of C3H/HeJ and C3H/HeN mice at the dose of 500 micrograms/ml in vitro, but did not show cytotoxicity for BHK-21 cells kidney cells of the Syrian hamster, CHO-K1, ovary cells of the Chinese hamster, and CHL, lung cells of the Chinese hamster, at doses of 5 and 500 micrograms/ml. Gelation activity in the Limulus test was only observed at PAg concentrations over 100 ng/ml, which dose was 10,000 times that of lipopolysaccharide (LPS) of Escherichia coli O55:B5. Furthermore, an adjuvant activity of PAgs was not observed in the production of anti-sheep red blood cell antibody in mice. Mitotic conversion of spleen cells from C3H/HeJ and C3H/HeN mice was observed by the addition of PAgs in vitro. These results indicated that the biological properties of PAgs were different from those of LPS prepared from gram-negative enterobacteria, that PAgs had no endotoxic activity and that the biological safety of PAgs as vaccine was proved. PMID- 2261064 TI - Fatty acid profiles in the family Leptospiraceae. AB - Fatty acid profiles of six leptospira strains representative of genera, species, and serogroups within the family Leptospiraceae were determined by gas liquid chromatography (GLC) of fatty acid methyl ester (FAME) derivatives. The influence of methodological and biological variables on FAME profiles of the same strain was tested. FAME profiles were sharply affected by the fatty acid composition of the culture medium but not by the growth phase. Twenty-four FAME peaks were selected on the basis of their presence in repeated gas chromatographic runs of single strains. Inter-strain divergences of FAME profiles were quantified by linear regression analysis (LR). Step-wise divergences in FAME profiles were observed between strains at serogroup, species, and genus levels. PMID- 2261065 TI - Preparation of a latex reagent for the detection of anti-Staphylococcus aureus ribitol teichoic acid antibodies. AB - Purified S. aureus ribitol teichoic acid was covalently bound to carboxylated latex particles. The immunological properties of the polysaccharide antigen were preserved. The reagent obtained was used for the quantification of anti-ribitol teichoic acid antibodies by means of a direct and rapid agglutination test carried out on a slide. There was good correlation between the preliminary results of this test and those obtained with counter-immunoelectrophoresis (CIE). The method is faster and more sensitive than CIE. PMID- 2261066 TI - Characterization of haptoglobin-binding properties of streptococci of serological group G. AB - Two group G streptococcal cultures (G 10187, G 11122) with surface antigen T4 possess surface receptors for human haptoglobin (Hp). G 10187 additionally interacted with immunoglobulin G and albumin, G 11122 with fibrinogen and fibronectin. Binding of 125I-Hp 2-1 was time-dependent, saturable, reversible in the presence of unlabelled Hp and could be inhibited by unlabelled human-Hp 2-1, Hp 2-2, -Hp 1-1, Hp-hemoglobin complexes and by Hp preparations from pigs, horses and rabbits. The Hp binding sites could be destroyed by heat treatment (95 degrees C) and by proteolytic treatment of the bacteria. Hp binding sites were solubilized from group G streptococcal surface by heat treatment of the bacteria at acid pH and subsequently isolated by affinity chromatography on Hp 2-1 sepharose. SDS-PAGE and Western blotting of the Hp binding proteins revealed numerous protein bands with 125I-Hp 2-1 binding activity. Specific antibodies against G streptococcal binding proteins prepared in chickens inhibited binding of 125I-Hp to group G and group A streptococci, but not to Actinomyces pyogenes. PMID- 2261067 TI - Methodological aspects of a microidentification technique for the differentiation of coagulase-negative staphylococci to species level. AB - The increasing number of coagulase-negative staphylococci (CNS) obtained from clinical material requires a biochemical identification on a broad basis in order to get a better determination of the clinical relevance of the single species. The method of differentiation presented is based on an inoculated microtiter plate provided with reagents and indicators which is evaluated by means of a coding system including most variations of the typical enzyme patterns. As a result of 7040 test series with 55 defined strains, a high degree of plausibility and reproducibility of the single reactions was found in 1320 tests under the recommended conditions. The biochemical patterns of 1380 strains taken from the diagnostic routine were established by means of this method. Comparisons with a commercially available system showed a large congruence of the single reactions and the results of identification. PMID- 2261068 TI - [Regeneration of bark of Chinese medicinal plants after large area girdling]. AB - This paper deals with the method of girdling, conditions of girdling, regeneration mechanism, and factors promoting bark regeneration. The results show that girdling is an effective way of tackling the problem of deficiency of woody medicinal plants in China. PMID- 2261069 TI - [Identification of plant morphology of herba Plantaginis in China]. AB - This paper deals with the identification of plant morphology of 18 Herba Plantaginis produced in China, of which 6 species are reported for the first time in China. Keys and diagrams for the identification are given. PMID- 2261070 TI - [Effects of fungi and its liquid extract on seed germination of Dendrobium hancockii Rolf]. AB - The experiment revealed that several species of fungi isolated from the protocorms of Orchidaceae notable promote the seed germination of Dendrobium hancockii. The seed germination rate amounts to over 20% when the seeds are incubated with fungi, but zero without incubation. Seed germination rate ranges from 40 to 70% when the incubation is affected in liquid extract of the cultural products of fungi, but the growth of protocorms and seedlings of Dendrobium hancockii is slower in liquid extract of fungi than on mycolia. PMID- 2261071 TI - [Effects of processing methods on the amounts of volatile oil of nutmeg and on isolation and characterization of the volatile oil constituents]. AB - In this paper, the authors investigated the effects of various processing methods, i.e., scalding in hot purified talc, simmering wrapped in flour in hot purified talc and stir-frying in smoking wheat bran, on nutmeg (Semen Myristicae) in terms of the quantities of the volatile oil. The experimental results revealed that the amounts of volatile oil contained in nutmeg vary remarkably with the lengths of cooking time and the fluctuation of temperature. Detected by GC-MS computer, 32 compounds of nutmeg were characterized, and their contents were determined by GC respectively. PMID- 2261072 TI - [Processing technique of American ginseng]. AB - The article deals with a new technique for processing American ginseng cultivated in China by far-infrared and moisture absorption. The qualities of processed product as per ton-quantity (including appearance, physical properties and chemical compositions) show no difference from those of American ginseng imported from U.S.A. and Canada. The mathematical model of dry-loss weight of American ginseng during processing is given in this article. PMID- 2261073 TI - [Preparation conditions for decoction of Epimedium grandiflorum Morr]. AB - The time, volume and method in preparing decoction of Epimedium grandiflorum have been studied by orthogonal design through the determination of icariin. The factors which influence decoction-making conditions are in the order of: volume greater than time greater than method. PMID- 2261074 TI - [Analysis of essential oils in roots and fruits of Angelica in Northeast China]. AB - The essential oils of roots and fruits of five species of Angelica have been examined and analysed by GC-MS-DS; 59 chemical compounds are reported, of which alpha-pinene, myrcene and p-cymene are common to all five species. This paper provides a scientific basis for developing the resources of this genus in the Northeast. PMID- 2261075 TI - [Chemical components of the essential oil from Ligusticum brachylobum Franch]. AB - 45 chemical components of the essential oil from Ligusticum brachylobum were identified, the main ones being alpha-pinene (45.46%), beta-pinene (18.01%) and limonene (8.19%), etc. In the essential oil, however, no ligustilide was found that makes an effective component of the essential oils from L. sinense cv. chuanxiong and from L. sinense. This result provides a basis for the quality evaluation of the drug. PMID- 2261076 TI - [Pharmacological study of Rubus parvifolius L]. AB - Aqueous extracts of Rubus parvifolius have been proved useful in shortening bleeding time and coagulation time in mice, shortening euglobulinlysis time in rabbits, inhibiting platelet thrombosis in rabbits in vivo, Rubus parvifolius increasing coronary flow in isolated rat heart, preventing rats from pituitrin induced changes of ECG and Rubus parvifolius increasing the tolerance of mice to hypoxia. The toxicity of Rubus parvifolius is small. PMID- 2261077 TI - [Antiarrhythmic effect of Oenanthe javanica (Bl.) DC. injection]. AB - The antiarrhythmic effect of Shuiqin (Oenanthe javanica) injection was studied in rats. An injection of 3 ml/kg iv could significantly antagonize the arrhythmias induced by aconitine and BaCl2, and decrease the rates of ventricular fibrillation and death induced by CaCl2. The results suggest that Shuqin injection has a significant antiarrhythmic effect on experimental rats. PMID- 2261078 TI - [Experimental study of anti-injurous effect of Cynanchum auriculatum Royle ex Wight on ozonic toxicity]. PMID- 2261079 TI - [Effects of baicalin and liquid extract of licorice on sorbitol level in red blood cells of diabetic rats]. AB - 10 streptozotocin-induced diabetic rats were treated with baicalin 150 mg/kg.d and liquid extract of licorice (LEL) 7.5 ml/kg.d (5 by each medicine) for a week. The results indicated that orally baicalin and LEL could dramatically reduce the sorbitol levels in red blood cells (123.7 +/- 28.6 to 72.5 +/- 21.8 and 116.9 +/- 25.2 to 80.5 +/- 23.8 nmol/g.Hb, respectively) without affecting blood glucose levels significantly. It is suggested that both medicines act by inhibiting aldose reductase. PMID- 2261080 TI - Nucleotide sequence and deletion analysis of the polB gene of Escherichia coli. AB - The polB gene encodes DNA polymerase II in Escherichia coli. The nucleotide sequence shows an open reading frame of 2,304 nucleotides coding for a protein of 88 kD. The protein initiation signal is preceded by a lexA box lying 2 nucleotides from the termination signal of araD, and begins with GUG 75 nucleotides after the termination of araD. The polB gene and the araD gene are transcribed in the same direction. Initiation of protein synthesis was confirmed by peptide sequence. We have also demonstrated that the polB sequence is lacking in some strains. We conclude that DNA polymerase II is not a required protein in the cell. Sequence comparisons show that DNA polymerase II is an alpha-like DNA polymerase. PMID- 2261081 TI - Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene. AB - Melanin concentrating hormone (MCH) is a key neuroendocrine peptide which is involved in the regulation of body color in teleost fish. Antigenically similar peptides exist in higher vertebrates including rodents and man. The precise function(s) of these peptides in these higher vertebrates has yet to be fully elucidated, although regulatory roles in stress-induced or corticotropin releasing hormone-stimulated ACTH release and/or water balance have been proposed. The salmon, rat, and human MCH cDNA clones have been isolated and sequenced. We isolated and characterized the structure of the rat MCH gene. In addition to providing the complete nucleotide sequence of this gene, we demonstrate that there is a single copy of this gene in the rat genome. The structure of the rat MCH gene indicates that the MCH mRNA is encoded by three exons. Using primer extension and RNase protection assays, the transcriptional start sites of hypothalamic MCH mRNA were determined, allowing us to define the promoter region of this gene. We also characterize the central nervous system distribution of expression of the MCH gene by Northern blot analysis, demonstrating that the MCH mRNA is found predominantly if not exclusively within the hypothalamus. PMID- 2261082 TI - Atlantic salmon (Salmo salar) serum albumin: cDNA sequence, evolution, and tissue expression. AB - Atlantic salmon serum albumin is one of the most abundant proteins in salmon liver, representing 1.6% of all clones in a cDNA library made from salmon liver RNA. The DNA from a number of clones was sequenced to reveal an open reading frame of 1,827 bases encoding a 608-amino-acid protein. The sequenced 5' untranslated region is 69 bases long and the 3' untranslated region contains two putative polyadenylation signals and poly(A) tail. Sequence analysis of different clones indicates the presence of a second cDNA for salmon serum albumin. Multiple alignments of salmon serum albumin deduced amino acid sequence with Xenopus laevis, rat, bovine, and human serum albumins shows significant conservation of cysteine residues. The triple domain structure of serum albumin proteins is maintained. Unlike mammalian systems where serum albumin expression appears to be specific to liver only, salmon serum albumin is expressed in muscle also. PMID- 2261083 TI - Simultaneous synthesis of multiple oligonucleotides using nucleoside-H phosphonate intermediates. AB - A semimechanized simultaneous synthesis of multiple oligonucleotides using nucleoside-H-phosphonates as intermediates was developed and applied to the preparation of hybridization probes. The synthesis could be done with equivalent results (about 98% average yield per cycle) using regenerated H-phosphonates. PMID- 2261084 TI - Alcohol-related birth defects in long- and short-sleep mice: postnatal litter mortality. AB - Alcohol sensitivity may influence the severity of alcohol-related birth defects (ARBD). To examine this hypothesis, pregnancy outcome and offspring development were examined in alcohol-sensitive Long-Sleep (LS) mice and alcohol-resistant Short-Sleep (SS) mice following prenatal ethanol exposure. Dams were intragastrically intubated twice per day (6 hr apart) with either 4.5 g/kg (20% w/v) ethanol (E) or an isocaloric amount of sucrose (S) on days 7 through 18 of pregnancy. An untreated control group (C) was maintained for each line. Results showed litter mortality at 10 days of age was greater for LS-E litters compared to both LS-S and LS-C litters. Litter mortality for SS-E litters did not differ from either SS-S or SS-C litters. Maternal weight gain, blood ethanol levels, and birth weight deficits were similar for ethanol-exposed LS and SS groups. These results suggest genetically based alcohol sensitivity influences the severity of ARBD. PMID- 2261085 TI - Classically conditioned ethanol stimulus control of a motor behavior. AB - Rats with extensive unilateral 6-hydroxydopamine lesions of substantia nigra rotate (turn in circles) in response to administration of dopamine agonists. Here apomorphine administration, but not single or repeated administrations of ethanol, resulted in rotation in such lesioned animals. When apomorphine and ethanol were administered simultaneously to lesioned animals, rapid contralateral rotation resulted. After five of these conditioning trials in which ethanol and apomorphine were paired, ethanol alone elicited apomorphine-like rotation. Saline administration did not result in rotation in the conditioned animals, indicating that ethanol rather than the injection procedure exerted stimulus control over the behavior. Control animals which were treated five times with apomorphine and ethanol in an unpaired manner showed no conditioned rotation to ethanol. PMID- 2261086 TI - Progression of neurological disease in thiamin-deficient rats is enhanced by ethanol. AB - The clinical and neuropathological consequences of either ethanol consumption or thiamin deficiency or both were examined in Wistar rats aged nine weeks divided into five groups and fed one of the following diets: a thiamin-replete (control) diet (A): a thiamin-fortified diet with water (B) or 15% ethanol (C); or a thiamin-deficient diet with water (D) or 15% ethanol (E). Rats fed diets A, B or C for 35 weeks showed no clinical signs of neurological disease at any stage and no significant brain pathology when harvested. Rats fed diets D and E progressed through a common sequence of clinical signs of neurological disease typical of acute thiamin deficiency, viz loss of coat condition, ataxia, opisthotonus and ultimately death within 10-23 weeks. The onset and progression of these stages of neurological disease were significantly earlier and faster (p less than 0.001 for proportion of opisthotonic and ataxic animals at weeks 10 and 15) in the thiamin deficient rats that received ethanol than in those that did not. At death, the brain pathology in these two groups was limited and similar. PMID- 2261087 TI - Suppression of ethanol intake in ethanol-preferring rats by 1,4-butanediol. AB - The oral administration of 1,4-butanediol (1,4-BD) at doses ranging from 100 to 300 mg/kg, twice daily, produced a dose-dependent reduction (40 to 85%) in the voluntary ethanol intake in rats selectively bred for high preference for ethanol. Treatment with 1,4-BD did not reduce total fluid intake. Repeated 1,4-BD administration (300 mg/kg twice daily for 7 days) suppressed ethanol intake almost completely. After suspension of 1,4-BD treatment, the inhibitory effect on ethanol intake remained significantly low for 2 days. 1,4-BD failed to inhibit aldehyde dehydrogenase to a concentration of 10 mM in rat liver homogenate. PMID- 2261088 TI - Prenatal alcohol exposure alters hippocampal slice electrophysiology. AB - Pregnant Sprague-Dawley rats consumed an ethanol-containing liquid diet containing 0%, 17.5% or 35% ethanol-derived calories (EDC) from gestation day 8 until parturition. A fourth group was fed standard rat chow as an ad lib diet control. Animals prenatally exposed to ethanol had lower birth weights and impaired passive avoidance learning at 17 days of age. At 90 days of age synaptic potentials in area CA1 were characterized electrophysiologically in hippocampal slices. Slices from ethanol-exposed rats had significantly greater paired-pulse facilitation compared to 0% EDC and ad lib controls. Histological examination of brains from litter mates did not indicate altered number, density or nuclear volumes for neurons in area CA1. These data indicate that prenatal ethanol exposure can result in abnormal hippocampal synaptic physiology and suggest that these changes may contribute to the learning impairments observed in rats following such exposure. PMID- 2261089 TI - Reduced sensitivity of hypothalamic-preoptic area norepinephrine and dopamine to testosterone feedback in adult fetal ethanol-exposed male rats. AB - Endocrine feedback of testosterone (T) in regulation of the hypothalamus is via the effects of T on the noradrenergic system. The current experiment was performed to determine the effects of fetal ethanol exposure (FEE) on the norepinephrine (NE) and dopamine (DA) content in the hypothalamic-preoptic area (HPOA) of adult male rats, and the response of NE and DA to T administration. Pregnant rats were exposed to diets containing either a liquid diet containing ethanol, a liquid diet containing sucrose isocalorically substituted for ethanol, or a chow and water diet. Male offspring were castrated or sham-operated at 45 days of age. The animals received either testosterone propionate (TP) or an oil vehicle. HPOA was collected at 55 days of age from each animal and NE and DA content was measured by HPLC-EC. There was no significant alteration of NE or DA content in the HPOA in FEE animals compared to catecholamine levels in animals derived from dams on the control diets. Castration had no significant effect on NE and DA content in the chow-fed or pair-fed animals. TP administration significantly reduced NE content only in the chow- and pair-fed animals but not in the FEE animals. DA content in the HPOA was not affected by castration, but TP administration also resulted in significantly reducing DA content in chow- and pair-fed castrate male rats but not in FEE castrate male rats. The results indicate that FEE alters the response of the noradrenergic and dopaminergic neurons in the HPOA to T administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261090 TI - Tolerance to ethanol-induced hypothermia in adult rats following postnatal ethanol exposure. AB - Rat pups of both genders were treated during the entire postnatal brain growth spurt (postnatal days 1-20) with ethanol (EE) utilizing an intragastric intubation technique. Two other groups of pups included isocaloric vehicle and handled control pups. Beginning on postnatal day 43 (TD1), and every seventh day subsequently (TD's 2, 3 and 4), the rats received an intraperitoneal dose of 2.2 g/kg ethanol. Their body temperatures were recorded at 0, 30, 60 and 90 minutes postinjection by use of a rectal probe. On the six days between measurements of ethanol-induced hypothermia, all rats were administered a daily dose of ethanol by intragastric intubation. Body growth of male and female pups was inhibited throughout the early treatment period. Body growth of adult females, but not males, was also depressed on TD's 1 and 2. Basal body temperature of EE male rats was selectively depressed at TD2, compared to the other groups. Although all groups showed tolerance to ethanol-induced hypothermia by TD2, there was a significant difference between males and females. Specifically, EE female rats showed a greater degree of tolerance when compared to EE males or control females. PMID- 2261091 TI - Novel versus familiar ethanol: a comparison of aversive and rewarding properties. AB - Rats were given a series of the conditioning trials during which sucrose solution was paired with ethanol which had previously been experienced on 0, 3, or 9 occasions. On each conditioning trial, the rats received a Taste Reactivity Trial, a Taste Avoidance Trial, and a Place-Conditioning Trial. After the rats had received 4 conditioning trials, they were given a Conditioned Place Preference Test, a Taste Reactivity (TR) Test, and a Conditioned Aversion Extinction Test. Only the group conditioned with novel ethanol demonstrated aversive TR responses, although all CS + groups eventually demonstrated suppressed ingestive TR responses and enhanced neutral TR responses. Familiarization attenuated, but did not eliminate, ethanol-induced CTAs. There was no evidence of place conditioning. PMID- 2261092 TI - Effects of fluoxetine and desipramine on palatability-induced ethanol consumption in the alcohol-nonpreferring (NP) line of rats. AB - Three groups of NP rats (n = 5/group) received food, water and one of 3 Polycose solutions ad lib. One group received a solution containing 3% (w/v) Polycose, 0.125% (w/v) saccharin, 0.5% (w/v) NaCl (3% POL solution) to which ethanol was gradually added over three weeks until the concentration of 10% (v/v) ethanol (E) was reached (3% POL + E group). Alcohol ingestion by the 3% POL + E group reached an average of 9 g of ethanol/kg b. wt./day; the rats attained average blood alcohol concentrations of 61 +/- 8 mg%. One control group (3% POL) was given the same solution as above but without ethanol. The second control group (17% POL) had access to a 17.6% Polycose solution supplemented with 0.125% saccharin and 0.5% NaCl and was isocaloric to the 3% POL + E solution. Although the three groups differed significantly in the amounts of food and Polycose solutions consumed, their total caloric intakes were equivalent. The IP administration of the serotonin (5-HT) uptake inhibitor fluoxetine (5 and 10 mg/kg) significantly reduced drinking of the group receiving the 3% POL + E solution by 23% and 67%, respectively, but did not alter intakes of the Polycose solutions by the 3% or 17% POL control groups. The IP administration of the norepinephrine (NE) uptake inhibitor desipramine (5 and 10 mg/kg) significantly reduced intake of the Polycose solution by the 17% POL group by 52 and 83%, respectively, but only the 10 mg/kg dose attenuated drinking of the solutions by the 3% POL and 3% POL + E groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261093 TI - Interaction of alcohol and stress at the cardiovascular level. AB - Research on the interaction of alcohol and stress on the cardiovascular system published since 1981 is reviewed. Important variables that can modify the interaction of alcohol and stress are also discussed. Consistent findings have come from studies on stress-induced tachycardia which has been shown to be decreased by alcohol ingestion. Evidence from clinical, cohort, case-control, epidemiological research indicates that long-term ingestion of alcohol is associated with lower risk of coronary heart disease. Less clear is the association of the risk of hypertension and alcohol ingestion. Primarily in women, there might be a threshold low level of alcohol consumption which is not associated with the development of hypertension. With some stressors, alcohol may depress the stressor-induced elevation of plasma catecholamines. Mechanisms believed to mediate the described alcohol-stress interaction are discussed. Existing evidence support the following mechanisms: mediation via changes in plasma lipoproteins in the case of coronary heart disease and changes in plasma calcium levels for the blood pressure effects. PMID- 2261094 TI - Moderate alcohol consumption and platelet aggregation in healthy middle-aged men. AB - Changes in platelet aggregation have often been proposed as an explanation for the protective effect of moderate alcohol consumption on the development of coronary heart disease, observed in epidemiological studies. To test the tenability of this assumption, the acute effect of moderate alcohol consumption on platelet aggregation was studied in eight healthy middle-aged men in a controlled study. The intake of alcohol consisted of two glasses of red wine at dinner and two glasses of distilled liquor (Hollands gin), combined with a snack, before bedtime. No acute effects of moderate alcohol consumption on platelet aggregation were observed. PMID- 2261095 TI - Thermoregulation at a high ambient temperature following the oral administration of ethanol in the rat. AB - This study was designed to assess the thermoregulatory mechanisms responsible for the elevation in body temperature following ethanol administration when exposed to a high ambient temperature (Ta). Male rats of the Fischer 344 strain were gavaged with 20% ethanol at doses of 0, 2.0, 4.0, 6.0, or 8.0 g/kg and were then placed in an environmental chamber set at a Ta of 37 degrees C. Metabolic rate normalized to body mass0.75 (MR), evaporative water loss (EWL), and motor activity were recorded for 60 min. Ethanol elicited a significant increase in colonic temperature and decrease in MR, EWL, and motor activity. Ethanol also significantly reduced the quantity of evaporated water per milliliter of oxygen consumed (E/M). Multiple linear regression analysis indicated that the two major factors which were associated with the ethanol-induced elevation in body temperature were an increase in MR and a decrease in E/M. Visual observation of behavior indicated that the normal grooming of saliva onto the fur during heat stress was impaired in ethanol-treated animals. Thus, during exposure to a high Ta, the acute ethanol-induced elevation in body temperature appears to be attributed to a suppression in both autonomic and behavioral mechanisms of heat dissipation. PMID- 2261096 TI - Antimicrobial prophylaxis for cerebrospinal fluid fistula. PMID- 2261097 TI - CSF fistula and the surgeon. PMID- 2261098 TI - Aneurysm rebleeding after treatments that leave the aneurysm sac patent. AB - Three operations that leave the aneurysm sac patent have been used to treat ruptured intracranial aneurysms: carotid ligation, anterior cerebral artery ligation and aneurysm wrapping. The rates of early rebleeding (0-6 months) for these operations are respectively less than 10, 3.9 and 8.6%. The long-term risks of rebleeding are at least 1% per year for anterior cerebral or carotid artery ligation and 1.5% per year for wrapping. Eighty per cent of rebleeds are fatal. Most aneurysms are still seen to be patent if angiography is performed after these treatments. Should patients who have had these operations be offered aneurysm clipping? PMID- 2261099 TI - Acute traumatic CSF fistulae: the risk of intracranial infection. AB - The management of acute traumatic cerebrospinal fluid (CSF) fistulae is still a matter of debate and hinges about what is perceived to be the risk of subsequent intracranial infection. We have therefore carried out a retrospective analysis of 160 cases of traumatic CSF leaks to assess the incidence, cumulative risk and prognosis of intracranial infection. The overall incidence of meningitis in this group before surgical dural repair was 30.6% (49/160), the cumulative risk exceeded 85% at 10 years follow-up and the meningitis was fatal in 4.1% (2/49). The recurrence of CSF leakage after initial spontaneous cessation was 7% and meningitis was recurrent in 30.6% (15/49). Prophylactic antibiotics had reduced the risk of meningitis from 61 to 34%. The commonest pathogen was pneumococcus and the CSF leakage had stopped within 7 days in 60% of those who developed meningitis and in 50% of those who did not develop meningitis. Meningitis is still a serious complication of post-traumatic CSF fistulae and is potentially fatal despite modern therapeutic agents. PMID- 2261100 TI - Complications related to pre-craniotomy shunts in posterior fossa tumours. AB - Among 344 patients with posterior fossa tumours treated from 1979 to 1986 a ventriculoperitoneal, or, less commonly, a ventriculatrial shunt was inserted in 164 cases pre-operatively. Haematoma following the insertion of a shunt was found to be an important cause of deterioration. While the occurrence of cerebrospinal fluid leak (p less than 0.3) and pseudomeningocele (p less than 0.01) was more frequent in the non-shunted cases, seizures (p less than 0.01) were found to occur more frequently in the shunted cases. PMID- 2261101 TI - Avoiding empiric therapy for brain masses in Indian patients using CT-guided stereotaxy. AB - Empiric therapy, especially antituberculous therapy, is frequently given to Indian patients with brain masses. This report documents our experience in avoiding such therapy using CT-guided stereotaxy. Out of 101 procedures done on 99 patients with brain masses, 80 were done to obtain a histological diagnosis and 21 for therapeutic purposes. There was no mortality and 2% morbidity. A positive diagnosis was obtained in 94% (75/80) of patients undergoing a biopsy. Diagnosis of tuberculous lesions was based mainly on the presence of acid-fast bacilli in the biopsy specimen or pus. In six patients the radiological diagnosis was wrong and in one the diagnosis was not certain. Inappropriate therapy was given to three patients, on the basis of a CT or MRI scan, before a biopsy was done. It is essential that a histological diagnosis be obtained in all patients with brain masses and there is no role for empirical therapy except in isolated cases. PMID- 2261102 TI - Percutaneous stereotactic brain tumour biopsy and cyst aspiration with a non invasive frame. AB - A non-invasive Stereoadapter was used for stereotactic CT-guided percutaneous brain biopsy in 18 patients with 16 solid tumours and four cysts. The Stereoadapter was mounted on the patient's head using ear plugs and a nasion support. After the CT study, the Stereoadapter was detached. The target was simulated on a phantom base and a probe carrier attached to the Stereoadapter. For surgery, the Stereoadapter with the probe carrier was remounted to the patient's head. Local anaesthesia was mainly used. Tissue samples were aspirated with a 2 mm diameter Sedan-Nashold biopsy cannula, introduced through a twist drill hole. Conclusive histological/cytological diagnosis was obtained in 16 of the 20 lesions. The new method proved to be reliable and quick. Since the imaging study and the surgery could be separated in time and place, the biopsy procedure was less time-consuming than previous methods of stereotactic biopsy using an invasive frame. PMID- 2261103 TI - Computerized tomographic stereotaxy in the management of 200 consecutive intracranial mass lesions. Analysis of indications, benefits and outcome. AB - Two hundred consecutive stereotactic procedures were performed. These were 153 biopsies and 43 therapeutic procedures. The latter included aspiration of craniopharyngiomata, arachnoid cysts, deep-seated abscesses, and the destruction of colloid cysts. Cryogenesis was used to treat an arteriovenious malformation (AVM) in one case. In four cases, the system was used to locate lesions during open surgery. Leksell stereotactic systems were used throughout. The ages of the patients ranged between 12 months and 83 years. Overall, in 35% of biopsies the preoperative diagnosis was not confirmed. When the provisional diagnosis was glioma 70% were confirmed; 21% of them were benign, with 9% some other form of malignancy. Biopsy provided tissue on which a histological diagnosis could be made in 140 procedures. In eight cases the biopsy was repeated and in seven cases a positive diagnosis was subsequently made. Mortality was 1%; there was transient deterioration postoperatively in 5% and prolonged deterioration in 1%. These observations suggest that stereotactic surgery is far superior to freehand burr hole biopsy in the management of these lesions. No radiation treatment should be considered without histological confirmation. PMID- 2261104 TI - Bone flap replacement vs acrylic cranioplasty: a clinical audit. AB - A 5-year retrospective study comparing bone flap replacement with acrylic cranioplasty was carried out. There was no significant difference in the high infection rates associated with the two procedures. We suggest that antibiotic impregnated acrylic cranioplasty may be the safest and best surgical procedure based on the orthopaedic experience with gentamicin-impregnated cement in joint replacement surgery. PMID- 2261105 TI - Misleading CT scans: a report of two cases. AB - Two patients who appeared to have suffered from intracranial haemorrhage are presented. Their clinical histories and computed tomographic scans were supportive of the diagnosis of intracranial haemorrhage. However, both patients were found to have infected cerebrospinal fluid. PMID- 2261106 TI - Craniospinal neurenteric cyst. AB - The case of a 40-year-old male with a neurenteric cyst located anterior to the brain stem and to the C1-C2 levels of the spinal cord is presented. The cyst was successfully removed by a transoral approach. The case is discussed and literature reviewed. PMID- 2261107 TI - Successful removal of an angiographically occult arteriovenous malformation of the ventral medulla. AB - A case with an angiographically occult arteriovenous malformation (AVM) of the ventral medulla presenting with progressive motor and sensory deficits is reported. The AVM, about 1 x 1 x 0.5 cm in size, accompanied by intramedullary haematoma, was successfully removed through a small incision placed in the right ventrolateral medulla between the vagus and the hypoglossal nerves. The patient's neurological symptoms improved after surgery. PMID- 2261108 TI - Miniplate osteosynthesis in cranial skeletal fixation. AB - The use of miniplate osteosynthesis provides a three-dimensionally stable form of fixation for cranial skeletal defects secondary to trauma or surgery. They are easily contoured and are thus able to support the bone fragments in the correct anatomical position. Miniplates of 0.9 mm thickness are sufficient to provide stable fixation without causing significant displacement of the overlying soft tissues. Plating thus provides excellent stability and cosmesis. PMID- 2261109 TI - Extradural brucellosis granuloma with 'subtle' spondylosis: a rare cause of spinal cord compression. AB - A rare case of an extradural brucellosis granuloma in the thoracic region is presented. Medical treatment delayed surgical intervention and led to total paraplegia with sphincteric disturbance despite improving serum antibody titres. However, delayed neurosurgical intervention resulted in near-total clinical recovery. Early surgical intervention in cases of significant spinal cord compression due to an extradural brucellosis granuloma with a progressive neurological deficit is recommended. PMID- 2261110 TI - Perimesencephalic ependymal cyst. PMID- 2261112 TI - Bibliography of the current world literature. PMID- 2261111 TI - A low cost modification of an old Liksell stereotaxic frame to allow CT-guided stereotaxy. PMID- 2261114 TI - Monitoring HIV trends in injecting drug users: an Italian experience. AB - To examine the incidence and prevalence of HIV infection, we studied a large sample of intravenous drug users (IVDUs) attending a drug dependency unit in Rome over the period 1985-1989. The annual prevalence of HIV antibodies remained stable over the 5-year period. However, a seroconversion study conducted on 302 subjects consistently attending the same facility showed a continued occurrence of HIV seroconversion, although the incidence declined from 8.9 per 100 person years in 1985-1987 to 5.3 per 100 person-years in 1987-1989. The cumulative incidence of HIV seropositivity, estimated by the Kaplan-Meier survival technique, was higher in female than in male IVDUs. The findings show that the use of both incidence and prevalence data to monitor the trend of HIV infection allows a better understanding of the current viral spread among IVDUs. PMID- 2261115 TI - AIDS in the minds of Swedish people: 1986-1989. AB - In order to assess changes in knowledge, attitudes and behaviour related to AIDS, annual mail surveys (1986-1989) were sent to random samples of the general public, aged 16-44 years. In total, 16,900 individuals were sampled, with an average response rate of 71%. Knowledge about the major routes of infection was generally good during the entire study period. The fear of unverified infection risks and of contact with HIV-infected people decreased during the period studied, but still remained high in 1989. Over the entire period, respondents expressed a strong fear concerning the spread of HIV in the population. Although an increasing percentage of respondents reported altered sexual habits as a result of fear of AIDS, overall sexual behaviour did not change sufficiently to reduce the risk of spread of any sexually transmissible disease. Progress toward knowledge, attitudes, and behaviour aimed at prevention of transmission of infection and unnecessary fear and counteraction of prejudice was most rapid during the middle of the study period when public debate concerning AIDS was at its peak. Knowledge and attitudes did not change during the last year of the study, but, in some respects, reverted to previous levels. PMID- 2261113 TI - Impact of maternal HIV infection on obstetrical and early neonatal outcome. AB - In a case-control study of 177 HIV-seropositive and 326 seronegative women and their newborns in Nairobi, Kenya, maternal HIV infection at term was independently associated with travel to other African countries [odds ratio (OR) 4.9, P less than 0.0001], history of a blood transfusion since 1980 (OR 3.5, P = 0.01), history of more than one sexual partner in the previous 5 years (OR 1.8, P = 0.02) and unmarried status (OR 1.8, P = 0.02). Neonates of HIV-positive and HIV negative women differed little with respect to occurrence of congenital malformations, stillbirths, in-hospital mortality, sex, APGAR score, or gestational age. However, the mean birth weight of singleton neonates of HIV positive women was significantly lower than that of controls (3090 versus 3220 g, P = 0.005), and birth weight was less than 2500 g in 9% of cases and 3% of controls (OR 3.0, P = 0.007). Among neonates of HIV-seropositive women, birth weight was less than 2500 g in 17% if mothers were symptomatic and 6% if mothers were asymptomatic (OR 3.4, P = 0.08). PMID- 2261116 TI - Pneumocystis carinii pneumonia treated with eflornithine in AIDS patients resistant to conventional therapy. AB - Eflornithine (DFMO) was used to treat 31 AIDS patients with confirmed Pneumocystis carinii pneumonia who had clinically failed treatment with pentamidine, sulphamethoxazole-trimethoprim or both agents as their first-line therapy. Twenty-one of 31 (68%) responded to second-line treatment with 400mg/kg per day of eflornithine. Five patients discontinued treatment because of bone marrow toxicity. Eflornithine appears to be a useful salvage therapy in patients failing first-line treatments. PMID- 2261117 TI - Seroepidemiology of HIV-1 infection in a Catalonian penitentiary. AB - A seroepidemiological study of HIV-1 infection was carried out among all the subjects who were imprisoned in a correctional centre in Catalonia (Spain) between October 1987 and April 1988. Six hundred and thirty-one inmates (male, mean age 19.1 +/- 1.7 years) were surveyed. The overall prevalence of HIV-1 infection was 33.6%. Statistically significant differences were observed between intravenous drug users (IVDUs) and non-IVDUs (P less than 0.0000001) and between regular and irregular IVDUs (P less than 0.000001). The age at which the person started using drugs and the length of time spent in prison were also significantly associated with the prevalence of infection. No other variables, except the higher prevalence among the gipsy ethnic group, showed any statistically significant association with HIV-1 infection. PMID- 2261118 TI - Fibrinogen concentration in asymptomatic HIV-infected individuals. PMID- 2261119 TI - Maintenance therapy of oropharyngeal candidiasis in HIV-infected patients with fluconazole. PMID- 2261120 TI - Single-dose therapy for esophageal candidiasis with fluconazole. PMID- 2261121 TI - Prevalence of pulmonary toxoplasmosis in HIV-infected patients. PMID- 2261122 TI - The effect of fusidic acid on Tanzanian patients with AIDS. PMID- 2261123 TI - High prevalence of indeterminate western blot tests for antibodies to HIV-1 in Tanzania. PMID- 2261124 TI - HIV-1 and HIV-2 antibodies in Nigerian populations with high- and low-risk behaviour patterns. PMID- 2261125 TI - Adult perception of risk, risk behaviour and HIV/AIDS: a focus for intervention and research. PMID- 2261126 TI - Complement-mediated enhancement of HIV-1 infection of the monoblastoid cell line U937. AB - To assess the role of complement and complement receptors in HIV-1 infection of monocytes and macrophages, we studied the infectivity of HIV-1, isolated from the peripheral blood of a patient with subacute AIDS-related encephalopathy, on the human monoblastoid cell line U937. HIV-1 and HIV-1-infected cells were capable of activating the complement system via the classical and the alternative pathways, respectively. Low concentrations of HIV-1 were able to infect U937 cells more easily in the presence than in the absence of complement. At higher virus concentrations, infectivity was no longer facilitated by the presence of complement. Infection of U937 cells was reduced in the presence of any of the monoclonal antibodies (MAbs), OKT4a (anti-CD4), OKM1 (anti-CR3), or M522 (anti CR3). A combination of all three of these MAbs reduced the infection by an even greater amount. These data indicate that complement receptors may be a port of entry for complement-coated HIV-1. PMID- 2261127 TI - Extrapulmonary and disseminated tuberculosis in HIV-1-seropositive patients presenting to the acute medical services in Nairobi. AB - We studied 506 consecutive adult acute medical admissions to hospital in Nairobi; 95 (18.8%) were seropositive for HIV-1, and 43 new cases of active tuberculosis (TB) were identified. TB was clearly associated with HIV infection, occurring in 17.9% of seropositive patients compared with 6.3% of seronegatives [odds ratio (OR) 3.2; 95% confidence limits (CL) 1.6-6.5]. Extrapulmonary disease was more common in seropositive than seronegative TB patients (nine out of 17 versus five out of 26; OR 4.7; 95% CL 1.01-23.6); this accounted for most of the excess cases of TB seen in seropositive patients. Mycobacteraemia was demonstrated in two of eight seropositive TB patients but in none of 11 seronegative TB patients. No atypical mycobacteria were isolated. The World Health Organization (WHO) clinical case definition for African AIDS did not discriminate well between seropositive and seronegative TB cases. Five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating, compared with only one out of eight seronegative tuberculous women. An association between recent childbirth, HIV immunosuppression and the development of TB is suggested. PMID- 2261129 TI - Bibliography of the current world literature. PMID- 2261128 TI - Immunological changes in primary HIV-1 infection. AB - Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2 microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection. PMID- 2261130 TI - Heterosexual transmission of HIV-1 among employees and their spouses at two large businesses in Zaire. AB - To better understand the reasons why up to 80% of all HIV-1 infections in Zaire, but less than 5% in North America and Europe, are acquired through heterosexual transmission, and to assess the impact of HIV-1 infection on a large urban African workforce, we enrolled 7068 male employees, 416 female employees and 4548 female spouses of employees at two large Kinshasa businesses (a textile factory and a commercial bank) in a prospective study of HIV-1 infection. The HIV-1 seroprevalence rate was higher in male employees (5.8%) and their spouses (5.7%) at the bank than among male employees (2.8%) and their spouses (3.3%) at the textile factory. At both businesses HIV-1 seroprevalence was higher among employees in managerial positions (5.0%) than among workers in lower-level positions (3.0%; P less than 0.0001). In a multivariate analysis of male employees, receipt of a transfusion, a history of genital ulcer disease, working at the bank, urethritis, or being divorced or separated were independently associated with HIV-1 infection. During 1987 and 1988, AIDS was the most common cause of death among recently employed workers, accounting for 20 and 24% of all deaths at the textile factory and the commercial bank, respectively. The HIV-1 seroprevalence rate was higher among female workers (7.7%) than among the spouses of male workers (3.9%; P = 0.001). In multivariate analysis of the wives of workers, having an HIV-1-seropositive spouse, receipt of a blood transfusion, or a history of genital ulcer disease were independently associated with HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261131 TI - HIV-1 and pregnant women: associated factors, prevalence, estimate of incidence and role in fetal wastage in central Africa. AB - The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage. PMID- 2261132 TI - Recreational drug use and sexual behavior change in a cohort of homosexual men. The Multicenter AIDS Cohort Study (MACS). AB - The relationship between use of recreational drugs and high-risk (HIV transmitting) homosexual behavior was examined in the Multicenter AIDS Cohort Study (MACS) population. Among the 3916 men who completed both the baseline (1984) and first 6-month follow-up evaluations and were sexually active during the 6 months prior to enrollment, self-reported use of each of 10 classes of recreational drugs in conjunction with sexual activity was analyzed for both cross-sectional and prospective relationships with pattern of sexual behavior using a four-level sexual risk behavior index. At baseline, the proportion of men in the highest risk category (unprotected anal exposures with multiple partners) increased from 36 to 85% when men not using any drugs to men using three or more drugs plus volatile nitrites were examined. In multivariate logistical analyses, volatile nitrite use was significantly associated with failure to maintain or attain lower sexual risk levels after controlling for the effects of age, educational level and numbers of high-risk partners. These results suggest that volatile nitrite use may play an important role in the association between recreational drug use and high-risk sexual behavior among homosexual/bisexual men. PMID- 2261133 TI - Sleep disturbances in HIV-infected homosexual men. AB - To provide a better understanding of the etiology of subjective sleep complaints in HIV-infected individuals, a study to evaluate sleep/wake disturbances in 10 healthy HIV-infected male volunteers was performed. All subjects were HIV infected but had no history of AIDS-related infections, and considered clinically asymptomatic. Interviews and sleep questionnaires revealed sleep complaints in nine subjects. Five healthy HIV-seronegative male subjects, with no history of sleep complaints, were also evaluated. Sleep architecture analyses detected that, in comparison to published normative data and to negative controls, there was a significant increase in the total percentage of slow wave sleep (SWS) and an increase in the percentage of SWS in the later sleep cycles. When compared with normative data, an increase in stage 1 shifts, rapid eye movement (REM) periods, and arousals were also observed in the HIV-infected group. Significant decreases in sleep latency, total percentage stage 2 sleep, and average REM durations were also observed in the HIV-infected group compared with normative data. These sleep architecture abnormalities could not be attributed to known sole primary sleep disorders, first night effect, medications, anxiety or depression. This study indicates that sleep disturbances occur early in the course of HIV infection and suggests that the observed alterations of sleep physiology may be a consequence of central nervous system involvement and/or immune defense mobilization in the early phases of HIV infection. PMID- 2261134 TI - Enhancement of erythrocytic adenosine deaminase following treatment of AIDS related complex/AIDS patients with zidovudine. AB - The levels of adenosine deaminase (ADA) were determined in the erythrocytes of 10 patients with sexually transmitted HIV-1 infection [five cases with AIDS-related complex (ARC) and five with AIDS] before and after therapy with zidovudine (azidothymidine; AZT). A linear increase in ADA activity was observed during the second and third months of zidovudine treatment, with a final increase of about threefold after 3 months of drug administration. The concentration of adenosine triphosphate (ATP) was significantly lower in the erythrocytes of the same group of patients with respect to healthy controls, and a further decrease was noted after 3 months of zidovudine treatment. The results obtained indicate that treatment of ARC/AIDS subjects with zidovudine induces metabolic changes which could be responsible for the development of anaemia, an adverse effect frequently associated with zidovudine therapy. PMID- 2261135 TI - World Health Organization quality assessment programme on HIV testing. AB - A serum panel comprising 19 samples of known (five positives and 14 negatives) but undisclosed HIV-1-antibody content was distributed to 30 national reference laboratories for HIV serology. In order to simulate normal circumstances of referral, participants were asked to test the panel for HIV-1-antibody status using their normal procedures. Results of testing were returned by 28 participants. There were great variations in the number and combinations of tests used. The number used ranged from one to five assays per laboratory and none of the 24 laboratories using two or more tests employed the same combination. A high average success rate of 99% was seen with the positive samples. More errors occurred with the negative samples, with an average of 87% correct negative reports. Only four of the 14 negative specimens were reported as negative by all participants. PMID- 2261136 TI - Poverty and HIV seropositivity: the poor are more likely to be infected. AB - We analyzed demographic and behavioral risk factors for HIV seropositivity using data from 3601 clients of the main HIV counseling and testing clinic for high risk people in Seattle, Washington, USA. Clients with lower income were found to be more likely to be HIV seropositive, before and after controlling for other demographic and risk factors with logistic regression. This result supports the hypothesis that the impoverished are at increased risk for HIV infection due to the physical and social circumstances in which their poverty places them. These may include poor access to risk-reduction information and less support for implementation of risk-reduction strategies. PMID- 2261138 TI - Eosinophils, HIV infection and zidovudine. PMID- 2261137 TI - Therapy for HIV-1-related nephritis with zidovudine. PMID- 2261139 TI - Exclusion of blood donors by country of origin and discrimination against black foreigners in the USA. PMID- 2261140 TI - Renal cell adenocarcinoma associated with AIDS-related Kaposi's sarcoma. PMID- 2261141 TI - The limitations of the concept of needle sharing: the practice of frontloading. PMID- 2261142 TI - Inhibition of HIV replication by derivatives of naphthalenedisulfonic acids. PMID- 2261143 TI - Zidovudine overdose in an intravenous drug user. PMID- 2261144 TI - New angiotensin converting enzyme inhibitors. Their role in the management of hypertension. AB - The introduction of orally active angiotensin converting enzyme (ACE) inhibitors has revolutionized the treatment of hypertensive disorders and provided an effective alternative for the management of congestive heart failure (CHF). By interfering with the formation of angiotensin II, the active agent of the renin system, ACE inhibitors block the system's vasoconstrictive and sodium-retaining effects, with a consequent reduction in systemic blood pressure. The net effect is improved blood flow and reduced cardiac work. Thus, ACE inhibitors are likely to improve cardiac work capacity and quality of life. Their mechanism of action differs markedly from that of traditional antihypertensive agents which lower blood pressure while reducing cardiac output and blood flow. Since the primary action of ACE inhibitors is to block the renin system, a dramatic response to monotherapy suggests a large renin factor while the lack of a response suggests a low-renin state more amenable to treatment with a diuretic or calcium antagonist. Because of their many attributes, ACE inhibitors are increasingly used as first line therapy for the treatment of hypertension or CHF. The prototype orally active ACE inhibitor, captopril, is a sulfhydryl compound with a good safety profile at the recommended dosages but reported toxicity at higher dosages. Second-generation ACE inhibitors (eg, enalapril and quinapril) are more potent sulfhydryl-free esters with a greater affinity for the converting enzyme. These newer agents are pro-drugs requiring ester hydrolysis to form the active free acid compound.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261145 TI - Renal protective effects of angiotensin converting enzyme inhibitors. AB - Renal dysfunction and hypertension are closely associated. Hypertension causes approximately 25% of end-stage renal disease (ESRD) and develops in virtually every patient with advanced renal insufficiency from any cause. Although normalization of blood pressure can reduce mortality from uremia and ameliorate the progression of renal impairment in patients with established renal insufficiency from hypertension and diabetes, antihypertensive therapy alone is not totally effective in preventing progressive compromise of renal function- especially in blacks and diabetics, who are at high risk for developing ESRD. Of particular promise is the rapidly increasing understanding of the intrarenal autocrine and paracrine functions of angiotensin II produced locally by a tissue renin-angiotensin system. Consistent and convincing experimental data have demonstrated that angiotensin II plays many roles in the control of renal function and the kidney's response to injury. The intrarenal effects of angiotensin II include: 1) increase in the efferent arteriolar tone, resulting in increased glomerular capillary pressure, 2) promotion of mesangial cell contraction, 3) stimulation of proximal tubular Na+ reabsorption, and 4) possible growth hormone effects leading to hypertrophy or hyperplasia of vascular smooth muscle. Because of their favorable intrarenal hemodynamic effects (particularly reduction of glomerular capillary pressure), ACE inhibitors may provide a renal protective effect in addition to their systemic antihypertensive effects. Clinical trials evaluating the effect of ACE inhibition on the progression of renal insufficiency in hypertensives and diabetics are currently under way. Favorable results could lead to a significant decrease in the morbidity and mortality associated with hypertension. PMID- 2261146 TI - Use of quinapril in the elderly patient. AB - Quinapril hydrochloride is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor that has been extensively tested and found effective when administered once-a-day to hypertensive patients of both sexes and all degrees of hypertension and cardiac compromise, including those with left ventricular hypertrophy, with and without congestive heart failure. Observations with earlier ACE inhibitors led to reports that this class of drugs was relatively ineffective in older hypertensive patients. To ascertain the role of quinapril (greater than or equal to 10 mg/day) in older patients, its blood pressure-lowering effects in 1,175 hypertensive patients less than or equal to 65 years of age were compared with those in 304 patients greater than 65 years of age. An excellent response was observed in patients greater than 65 years of age with mild to moderate hypertension (diastolic BP, 95 to 105 mm Hg) and moderate to severe hypertension (diastolic BP, 106 to 115 mm Hg). The reductions in blood pressure achieved with quinapril were at least comparable to those obtained in the younger hypertensives, and were numerically (but not statistically) greater in the mild to moderate group (-14 mm Hg v-12 mm Hg). In addition, the percentage of patients who experienced adverse experiences was lower in the greater than 65 group than in the less than or equal to 65 group (15% v 19%). The main adverse experiences reported included dizziness, headache, cough, fatigue, and hypotension. These findings indicate that quinapril is at least as safe and effective in older hypertensives as in younger patients. PMID- 2261147 TI - Quinapril in chronic heart failure. AB - Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound. PMID- 2261148 TI - Elevated insulin, norepinephrine, and neuropeptide Y in hypertension. AB - To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels. PMID- 2261149 TI - Immunohistochemical study of vascular lesions in severe hypertension induced by DOCA and salt administration to spontaneously hypertensive rats. AB - In order to evaluate whether immunoglobulin deposition in vessels plays some role in the development of vascular lesions in severe hypertension, an immunohistochemical study was performed in spontaneously hypertensive rats (SHRs), to which deoxycorticosterone acetate (DOCA) and salt were administered. DOCA and salt rapidly induced severe hypertensive vascular lesions, including necrotizing arteriolitis and productive endarteritis. In these rats, considerable deposits of IgG and IgM were found in the small arteries and arterioles of the kidneys. These deposits were accompanied by complement (C3), and could be eluted by acid incubation. They were localized in periodic acid-Schiff-positive insudative lesions, which were thought to be an early phase of the hypertensive vascular lesions. These results suggest that the immunoglobulins might be bound to an unknown antigen in the vascular lesions and that some immunological mechanism mediated by the immunoglobulins is involved in the development of vascular lesions in severe hypertension. PMID- 2261150 TI - Dietary calcium, vascular reactivity, and genetic hypertension in the Lyon rat strain. AB - In order to examine the relationship existing between dietary calcium and the development of hypertension, we developed a long-term study in the Lyon hypertensive rat strain (LH) and two control strains, the Lyon normotensive (LN) and low blood pressure rats (LL) given enriched (HCa, 2.5%), deprived (LCa, 0.03%) and normal (NCa, 0.6%) calcium diets. Evolution of body weight, systolic blood pressure (BP), plasma calcium and magnesium was monitored from 4 to 23 weeks of age. Total cardiovascular reactivity and contractile response of isolated aorta to norepinephrine were measured at 23 weeks of age. LH rats on HCa diet failed to develop hypertension (BP less than 150 mm Hg) whereas LH rats on LCa diet exhibited higher blood pressure levels than their controls fed the NCa diet. Moreover, in LN rats HCa diet slightly decreased BP whereas LCa had no effect. In the LL rats, on the contrary, only LCa diet slightly increased BP. In vivo responsiveness to NE was significantly higher in LH compared to LL and LN rats fed a NCa diet. HCa and LCa diets both induced a significant decrease in this response in LH rats. HCa diet increased the response in LN rats but decreased it in LL. In contrast, at the same age, the in vitro contractile response of isolated aorta to NE was significantly decreased in LH compared to LN and LL rats receiving NCa diet. Moreover in LH and LN rats on HCa diet the contractile response was markedly increased but no significant difference was observed with LCa diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261151 TI - Sodium sensitive and sodium retaining hypertension. AB - The differences between sodium sensitive and sodium retaining hypertension were theoretically considered using a water tank model of body fluid volume-blood pressure regulation. If an outlet valve is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume and output from the outlet, which represent mean arterial pressure (MAP), cardiac output (CO) and urinary Na+ excretion. The height of the outlet from the tank bottom and the size cross-sectional area, of the outlet correspond to the x-intercept and slope of the renal function (pressure-natriuresis) curve, respectively. In both nonsodium sensitive hypertension, due to the shift of the curve toward a higher blood pressure level (elevated height of the outlet) without change in the slope (size of the outlet), and sodium sensitive hypertension, due to the depressed slope of the curve (reduced outlet size), not only MAP (water level) but also CO (water volume) are increased, resulting in sodium retaining hypertension, if TPR (reciprocal of base area) remained unchanged, while CO is relatively unchanged, resulting in nonsodium retaining hypertension, if TPR is elevated. Thus, the MAP and its sensitivity to sodium intake is determined by the renal function curve. Since body fluid volume is determined by both the renal function curve and TPR, however, changes in TPR during the development of hypertension is a major factor in determining whether or not the body fluid volume has to change only a small amount or a large amount. Therefore, the sodium sensitivity of blood pressure and sodium retention must be considered separately. PMID- 2261152 TI - Hemodynamic and endocrine effects of mental stress in untreated borderline hypertension. AB - Mental arithmetic and mirror tracing were compared in 40 untreated patients with borderline hypertension, tested in random sequence in standardized protocols. Both tasks significantly increased systolic and diastolic blood pressure, heart rate, cardiac index, plasma renin, and decreased peripheral resistance. Mental arithmetic also increased cholesterol, triglycerides and HDL; plasma catecholamines were not changed significantly. Lipid changes were correlated with blood pressure changes. These methods will be useful in exploring the relationships between hemodynamic reactivity to stress, and the presence and progression of atherosclerosis, as well as testing the effects of antihypertensive drugs on stress-induced changes that may influence atherosclerotic complications of hypertension. PMID- 2261153 TI - The transient increase of urinary digitalis-like substance excreted during excess sodium intake in reduced renal mass rats. AB - Urinary immunoreactive endogenous digitalis-like substance (EDLS) excretion was studied in gradually reduced renal mass rats (RRM). Urinary EDLS increased immediately after the start of 1% NaCl ingestion, then it returned to the basal level 2 weeks later. Both urinary sodium excretion and urinary EDLS were significantly higher in 3/6 and 4/6 RRM than in control until 2 weeks after starting 1% NaCl. However, there was no difference in blood pressure between the groups. Transient EDLS increase may play an important role in maintaining sodium and water homeostasis, but its transient increase apparently does not contribute to blood pressure elevation. PMID- 2261154 TI - Protein kinase C and platelet reactivity in spontaneously hypertensive rats. AB - Since protein kinase C (PKC) plays an important role in the control of platelet biological responses, we investigated whether it can be involved in the enhanced platelet reactivity to thrombin which is observed in spontaneously hypertensive rats (SHR) in comparison to that observed in controls (WKY). PKC activity was determined by measuring the phosphorylation of P47 protein (the endogenous substrate of PKC in the platelet). Mean effective concentration (EC50) values for phorbol ester and synthetic diacylglycerol (direct activators of PKC) were similar in SHR and WKY, thus revealing similar intrinsic activity of PKC in both rat strains. EC50 values for thrombin were approximately 30% lower in SHR v WKY. Enhanced PKC activity in SHR is likely the result of an increased diacylglycerol formation and release of Ca2+ from intracellular pools, consequent to an increased thrombin-induced phospholipase C activity. PMID- 2261155 TI - Vascular renin and hypertension. Uptake versus synthesis. AB - Conventional radioimmunoassay techniques demonstrated in the aortic wall a renin like activity which is derived from plasma but has a longer half-life than plasma renin. Blood pressure elevation after renin injection into nephrectomized rats correlates better with aortic renin than with plasma renin. Vascular and other extrarenal tissue can also synthesize renin. Using a ribonuclease protection technique for the detection of renin messenger RNA we have been able to demonstrate that a wide variety of extrarenal tissues contain the renin message. In at least two of these, the brain and the liver, renin messenger RNA levels are unaffected by changes in dietary salt or by changes in systemic blood pressure. Functional studies using isolated human resistance vessels also demonstrate the presence of renin-like activity by a contractile response to added renin substrate. It is suggested that extrarenal tissues therefore contain renin-like activity derived both from uptake and from local synthesis. These systems may be regulated in different ways and may carry out different functions. PMID- 2261156 TI - Alterations in renal medullary hemodynamics and the pressure-natriuretic response in genetic hypertension. AB - The concept that the kidney plays a major role in the long-term control of arterial pressure is based on the pressure-natriuretic response. According to this hypothesis, hypertension can only develop when the relationship between sodium excretion and arterial pressure is altered. Transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic forms of hypertension in the spontaneously hypertensive rat (SHR) and in the Dahl salt-sensitive (S) rat. Nonetheless, the factors responsible for "resetting the kidney in hypertension" remain unknown. We have reported that the pressure-natriuretic relationships of SHR and Dahl S rats of the Brookhaven and Rapp strains are shifted toward higher pressures prior to the development of the disease. Papillary blood flow is also reduced in very young "prehypertensive" SHR. Recent studies on the mechanism of pressure-diuresis indicate that it is mediated by inhibition of sodium reabsorption in the proximal tubule and/or thin descending limb of Henle of deep nephrons. It is also associated with changes in renal interstitial pressure and the pressure and flow in the vasa recta circulation. These observations suggest that an elevation in renal medullary vascular resistance may be responsible for shifting the pressure-natriuresis relationship toward higher pressures in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261157 TI - Importance of intraarterial blood pressure measurement in the evaluation of a new antihypertensive agent and the need to define hypertension also by this method. PMID- 2261158 TI - Perspectives on relational learning in mental retardation. PMID- 2261159 TI - Differences in development of visual and auditory-visual equivalence relations. AB - Five young adult females with mild mental retardation were given match-to-sample training and testing to develop four classes of equivalent stimuli: two classes containing three forms each and two classes containing one spoken nonsense syllable and two forms each. All subjects demonstrated development of all possible equivalence classes involving these stimuli. For 4 of 5 subjects, the classes that included auditory stimuli developed more rapidly than those that did not. PMID- 2261160 TI - Position-numeral equivalences and delayed position recognition span. AB - The role of equivalence class formation in delayed position recognition span performance was examined. Initially, the 3 subjects, adults with mental retardation, could not name the nine positions on the span test board. Thus, mnemonic facilitation of span performance based on position naming was not possible. Each subject, however, could name printed numerals and match these stimuli to their dictated names. Matching-to-sample training then established nine equivalence classes, each consisting of a position, a printed numeral, and the numeral name. In subsequent span tests, subject-produced numeral names led to dramatic increases in span scores. The equivalences provided precursors of a kind of verbal code that facilitated performance outside the training context. PMID- 2261161 TI - Teaching relational discrimination to individuals with mental retardation: some problems and possible solutions. AB - The problem of teaching relational discriminations to people with mental retardation was examined. The limitations of several commonly used teaching procedures were discussed and alternative approaches that derive from studies of simple-discrimination learning were described. Results of two preliminary studies were summarized that demonstrate the feasibility of these approaches and suggest new methods for teaching relational discriminations to individuals with developmental limitations. PMID- 2261162 TI - Long-term stability of equivalence relations in the absence of training or practice. AB - An adult male with mild mental retardation, whose laboratory history included training in a match-to-sample task on 16 arbitrary relations among 16 visual stimuli and 2 auditory stimuli, had performances that showed the development of 112 additional arbitrary relations that had never been reinforced. In the presented study on 2-year and 3-year follow-up tests for these derived relations, his performances remained stable despite the absence of opportunities to practice these relations between the tests and the absence of explicit feedback during the tests. The similarity to the long-term stability of language was discussed. PMID- 2261163 TI - Attentional functioning and relational learning. AB - Stimulus properties such as similarity-dissimilarity and novelty-familiarity are inherently relational and are embedded in ubiquitous stimulus contexts. Children with mental retardation and young children without mental retardation are particularly prone to failure on relational tasks such as oddity and match-to sample (Greenfield, 1985; Soraci et al., in press). Converging evidence from a number of studies suggest that a critical factor in the performance discrepancies between these and other children is a differential sensitivity to relational information. In these studies relational characteristics of stimulus arrays were enhanced in order to facilitate performances on such relational tasks. Findings indicate the theoretical and practical significance of perceptually based interventions that induce rapid discrimination learning. PMID- 2261164 TI - Home-like architectural features of residential environments. AB - Adults who had no experience in the area of mental retardation viewed slides of residential settings, five providing housing for people with mental retardation, and rated their "home-likeness" (1 = home-like, 5 = institutional). Of 55 two-way comparisons, the mean home-likeness ratings of 48 such pairs differed significantly from one another. A .98 log-linear correlation was found between number of residents in a given facility and institutional ratings. Of 26 features of living rooms studied in detail, furniture position, lighting type, and lighting flexibility were highly correlated with home-likeness, whereas building code-specific features and seating type were minimally related to home-likeness. PMID- 2261165 TI - Cognitive antecedents of imitativeness and persistence in children with mental retardation. AB - Two studies with children with mild mental retardation were conducted within the framework of the cognitive orientation theory, which describes how cognitive contents and processes guide behavior and thus enable behavior predictions and modifications. The studies were designed to test whether specific clusters of beliefs would predict imitation and persistence among individuals with mental retardation. Behavioral measures and questionnaires that assessed beliefs were administered. The belief scores were related significantly to the behaviors. Implications concerning motivation, the developmental-difference controversy, and individual differences were discussed. PMID- 2261166 TI - Thyroid eye disease. PMID- 2261167 TI - Vision screening in childhood. PMID- 2261168 TI - Graves' ophthalmopathy--a clinical review. AB - Graves' ophthalmopathy occurs in 2% to 7% of patients with Graves' disease with the major manifestations being proptosis, ophthalmoplegia, optic neuropathy and/or eyelid retraction. Although autoimmune in nature, the precise pathophysiology is unknown. The course of the ophthalmopathy is not influenced by the mode of treatment of the hyperthyroidism. In addition to restoration of the euthyroid state, the aims of treatment include relief of eye pain, correction of extraocular muscle dysfunction, protection of visual acuity and improvement of appearance. Specific therapy depends on the severity of the ophthalmopathy and varies from lubricating eye drops in mild disease to high-dose steroids and radiotherapy or decompressive surgery in severe cases. PMID- 2261169 TI - Orbital decompression in vision-threatening endocrine-related orbital disease. AB - The author's experience, limited to some twenty operations, mirrors the great experience of other clinics. The need to be aware of compressive optic neuropathy (CON) in endocrine-related orbital disease (EROD) is outlined. The value of orbital decompression in CON, severe corneal exposure and cosmetically unacceptable proptosis is mentioned. The author's technique is outlined. Three illustrative cases are briefly described. PMID- 2261170 TI - Vision-threatening thyroid orbital disease--the clinical features. AB - Thyroid orbital disease may threaten sight when acute proptosis causes corneal exposure or when enlarged extraocular muscles cause compressive optic neuropathy. The early clinical signs of thyroid optic neuropathy include loss of colour perception and visual field defects. The onset of thyroid optic neuropathy is difficult to predict and these clinical tests should be included in the routine examination of patients with thyroid orbital disease. PMID- 2261171 TI - Orbital myositis--a case report. AB - Orbital myositis is an idiopathic inflammatory condition involving the extraocular muscles. A case of presumed orbital myositis is presented, displaying typical features on orbital computed tomography, and a dramatic response to corticosteroid therapy. Atypical features of acute-on-chronic course, and concomitant sinus disease are discussed. A differential diagnosis of enlarged extraocular muscles is also discussed, and the benefits of corticosteroid trial before formal biopsy in the appropriate clinical setting is emphasised. PMID- 2261172 TI - Facial palsy--a leprosy surgeon's viewpoint. AB - Facial palsy is cosmetically unacceptable, whether affecting eyes or mouth. It endangers the vision. Both upper and lower facial paralysis can be surgically dealt with, using the temporal muscle and fascia. This produces satisfactory results in a relatively short period of time. PMID- 2261173 TI - Ophthalmic management of seventh nerve palsy. AB - The management of acute and established seventh nerve palsy is discussed with reference to corneal exposure, paralytic ectropion and the cosmetic defect. Details are given of how these can all be improved with relatively simple procedures which can be performed under local anaesthesia as an outpatient. PMID- 2261174 TI - Current management of ophthalmic zoster. AB - Most ophthalmic zoster occurs in healthy people and ocular complications occur in 50%. The mainstay of ocular therapy is topical steroid, but careful follow-up and withdrawal are essential. The place of systemic steroid therapy and acyclovir in immunocompetent patients with zoster is uncertain. PMID- 2261175 TI - Lateral orbitotomy--a review. AB - Lateral orbitotomy is the standard surgical approach to lesions in the middle third of the orbit, to many lesions in the posterior third of the orbit and to benign lacrimal gland tumours. The indications, surgical technique and complications are discussed. PMID- 2261176 TI - The eye and the hand: a clinical review. AB - The visual system is highly susceptible to involvement in many systemic disorders. Disorders of tissues common to the eye and the hand, such as vascular, connective and neural, may have striking clinical signs in both. Thus signs in the hand may provide useful diagnostic clues in the assessment of disorders of the visual system. The hand may even be causative in traumatic or infective eye diseases. This review provides a schema for a suitable hand examination and documents the eye and hand features of various common and uncommon disorders. The importance to the ophthalmologist of a careful hand examination is emphasised. PMID- 2261177 TI - Transient monocular blindness. AB - Transient monocular blindness (TMB) or amaurosis fugax is diagnosed when visual disturbance or loss (blindness, dimming, fogging, blurring) affects one eye for seconds or minutes. TMB may occur alone or in combination with transient hemispheric ischaemia (TIA). The cause of TMB is usually an atheromatous plaque at the carotid bifurcation in the neck liberating emboli or causing a temporary reduction in carotid and retinal blood flow. In most patients no embolus or ischaemic change is visible in the fundus. TMB should be investigated and treated in the same way as neurologic TIAs with emphasis on rapid detection of extracranial arterial disease, cardiac abnormalities and haematological disorders. PMID- 2261178 TI - A review of the use of Irlen (tinted) lenses. AB - Helen Irlen identified a syndrome defined as 'scotopic sensitivity' which it was claimed could be responsible for the inability of some people to read fluently and the symptoms of which could be ameliorated by the wearing of prescribed coloured lenses. The literature to date presents a confused and inconsistent picture concerning the use of the lenses. The literature (much of which is unpublished and difficult to obtain) is critically reviewed. Recent experimental evaluations of the lenses do not support the use of the lenses as a useful intervention for children with reading disabilities. PMID- 2261179 TI - Photoscreening to detect potential amblyopia. AB - Photoscreening to detect amblyopiogenic conditions is particularly applicable for the child under three years of age because conventional testing is difficult. We have designed an eccentric photoscreener that is inexpensive, easily used and requires only one diagnostic photograph. Some 231 infants and children were refracted and photoscreened and results compared in a blind study. Compliance was good and all cases of strabismus, amblyopia, and amblyopiogenic conditions were diagnosed. PMID- 2261180 TI - Random dot stereogram E in vision screening of children. AB - The random dot stereogram E (RDE) has been shown to be a simple and effective test for the detection of binocular abnormalities and defective visual acuity in children. We determined the validity of the RDE as a screening test for reduced visual acuity, amblyopia and strabismus in two separate populations of children. A nonselective group of 100 school children (aged 5 to 15 years) who presented consecutively to the ophthalmology department at Auckland Public Hospital were tested with the RDE. All cases of amblyopia and strabismus were detected by the RDE. Similar screening with the RDE test of 168 preschool children (aged three to four years) in the community resulted in an unacceptably high over-referral rate. The test was unreliable in the preschool age group because of difficulty in distinguishing between test failure and non-cooperation with the test. The low positive predictive value of the test in the younger age group suggests the test to be unsuitable for preschool vision screening. PMID- 2261181 TI - Paired comparison of contrast sensitivity in diffractive multifocal IOLs and conventional monofocal IOLs. AB - Multifocal intraocular lens (IOL) optics produce a retinal image of reduced contrast, which results from splitting incoming light between multiple focal points. This study sought to determine whether the reduced-contrast image results in functional loss of contrast sensitivity. Contrast sensitivity was measured in patients in the US Food and Drug Administration (FDA) study of the 3M Diffractive IOL, using the Pelli-Robson Letter Chart. Fifty-eight of these patients, including six from our clinic, were 'best-case' patients with no pathology, and also had paired multifocal/monofocal implants. Data from these 'best-care' patients with paired eyes indicate no functional difference in contrast sensitivity. Additional data obtained on our six patients with the Regan Low Contrast Charts suggest small predictable differences may exist for some patients at very low contrast levels. Further study is needed to determine whether these differences have functional significance. PMID- 2261182 TI - Trial of a disc lens for intercapsular cataract extraction. AB - The preliminary results are presented of a prospective trial of a new 'disc' intraocular lens. (Pharmacia Model CD801A). Forty-four lenses were implanted into the capsular bag using an intercapsular cataract extraction technique. The lens is a one-piece all-polymethylmethacrylate (PMMA) lens with a 6 mm biconvex optic. The optic sits within a 9 mm diameter flexible PMMA ring. Two haptic stalks link this flexible haptic ring to the optic. The lens was assessed for its ease of insertion, its rate of decentration, the incidence of posterior capsular opacity and its effects on pupillary function. Results of the trial at three months follow-up are presented. They show that the lens is easy to insert into the capsular bag even through small pupils. It is very easy to dial, placing no stress on the bag when doing so. The incidence of decentration of 1 mm or greater was 5%, and the incidence of posterior capsular fibrosis at three months was 2%. As predicted, the lens sits well back in the eye, clear of the pupil. PMID- 2261183 TI - Bullous keratopathy due to nonguttate corneal endothelial dystrophy. AB - Corneal oedema and bullous keratopathy may occur following intraocular surgery or arise spontaneously in nonguttate eyes. In some patients the fellow eye shows a relatively normal endothelial cell count with abnormal pleomorphism and polymegathism of the endothelial cells, while in others it shows a markedly lowered endothelial cell count with no evidence of corneal guttae. A survey of 17 such patients suggested the following classification. 1. Nonguttate corneal endothelial dystrophy with irregular endothelial cell morphology but a relatively normal endothelial cell count occurring following surgery (eight patients) or spontaneously (four patients). 2. Nonguttate corneal endothelial dystrophy with grossly reduced endothelial cell count occurring spontaneously (two patients). Three additional post-surgical patients showed a relatively normal endothelial cell count and only mild changes in the morphology of the corneal endothelium. These findings support the presence of a nonguttate corneal endothelial dystrophy in both the spontaneous and some of the post-surgical cases. PMID- 2261184 TI - The management of intraocular foreign bodies. AB - This study of 69 cases of retained intraocular foreign body confirms that eyes with anterior segment foreign bodies fare better than those with posterior segment foreign bodies, that eyes with smaller foreign bodies fare better than those with larger, and that the magnet is the safest method of removal. There is no evidence to support primary vitrectomy in every case of posterior segment foreign body. Computerised tomography is the best method of localisation, but a foreign body can be missed on computerised tomography, and a plain x-ray is still the best method of detection. PMID- 2261185 TI - Subretinal fluid in the diagnosis of posterior scleritis. AB - The etiology of subretinal mass lesions is very difficult to establish. A 28-year old man presented to us with an area of choroiditis, which progressed, despite corticosteroid and antibiotic therapy, to an exudative retinal detachment, secondary glaucoma and a painful blind eye. To develop a means of identifying the cause of such lesions, we did a subretinal fluid tap prior to enucleation. Cytopathology showed only inflammatory cells and the final histopathological diagnosis was that of a granulomatous scleritis. PMID- 2261186 TI - Day case surgery. PMID- 2261187 TI - Loa Loa disease. PMID- 2261188 TI - [Variable clinical course in cluster headache]. PMID- 2261189 TI - [Treatment of cerebrospinal fluid shunt infections using the Perrin and McLaurin technique. Analysis of 11 cases]. AB - Eleven patients with shunt infection (SI) of the cerebrospinal fluid in whom the SI was withdrawn and replaced by a new SI system with reservoir and intraventricular and parenteral antibiotic treatment were reported. The diagnosis was made by culture of the components of the SI and, or, the cerebrospinal fluid. In 9 cases the agent was a staphylococcus. The different therapeutic trials to treat SI infections can be summarized as follows: a) replacement of the SI by an external drainage, antibiotics, and reinsertion of the SI when the cerebrospinal fluid was sterilized; b) withdrawal of the SI and placement of a new SI in the same surgical procedure associated with intraventricular and systemic antibiotic treatment; and c) treatment with intraventricular and, or, systemic antibiotics. It has been demonstrated that the surgical approach (a and b) is more effective. In our series the procedure indicated in B was followed by the control of the infection in all cases. The follow-up of the surgical treatment was 1-3 years. The most currently used SI was the ventriculoperitoneal bypass. Their main complications are pseudocysts which are easily recognized by of abdominal echography and frequently revealed SI infection. Diagnosis and treatment of SI infections should take into account the type of complications and the most appropriate collaboration with other clinical departments. PMID- 2261190 TI - [Cerebral infarctions of the lacunar type in young adults]. AB - From a total number of 227 patients with lacunar infarcts of the brain assisted during a period of 7 consecutive years, 18 (8%) had an age equal or below 45 years. This group of patients represent 1.1% of strokes and 1.6 of the ischemic cerebral infarcts treated in a Neurology Service during the study period. Eleven patients (64%) were male. The most relevant cerebrovascular risk factors are: arterial hypertension (55%), cardiopathy (26%), and diabetes mellitus (11%). The most common syndrome was pure motor hemiparesis (61%), pure sensitive syndrome (22%), and atypical lacunar syndrome (17%). Computerized axial tomography of the brain was positive in 44.5% of cases. The mean systolic arterial pressure during the first 24 hours of the illness was significantly lower (p less than 0.03) in the young patients. Our results indicate that lacunar cerebral infarcts in young patients: a) are uncommon, and b) constitute a group with some differential clinical characteristics and with a better immediate prognosis with respect to the remaining patients with lacunar infarcts. PMID- 2261191 TI - [Acute confusional syndrome of unknown cause. Prospective study in the emergency room]. AB - In a prospective study conducted in the Emergency Area of a general hospital during a period of 6 months, the Neurology Service was consulted in 45 cases of acute confusional syndrome. Twenty nine of these patients had no immediate apparent etiology. Among the studied patients 5 had a subarachnoid hemorrhage, 4 suffered a central nervous system infection, 3 had a cerebral infarction, 3 presented a metabolic encephalopathy, and the remaining patients had variate etiologies. Clinical signs and symptoms were insufficient to establish the diagnosis and in several cases complementary tests were required (cerebral tomography and cerebrospinal liquid examination). Even in these cases the diagnosis could not be obtained in some patients. The clinical implications of the present findings were discussed. PMID- 2261192 TI - [Chronic toluene poisoning]. AB - The long-term inhalation of compounds in which toluene is the main ingredient leads to the damage of both central and peripheral nervous system. We present the case of a 24 year-old man who, sniffing these compounds since he was 17, slowly develops a variegated syndrome including psychiatric impairment, signs of bilateral pyramidalism, cerebellar and sensitive alterations, and peripheral neuropathy. CT scan, electrophysiological and laboratory modifications are reported. A comparative study with other reports is made, reviewing the associated pathology to this form of chronic intoxication, caused by the noxious action of each one of these substances or by their interaction. Liposolubility is established as the main pathogenic factor of this intoxication. PMID- 2261193 TI - [Multiple sclerosis lesions simulating an expansive process on CT]. AB - Patients with multiple sclerosis may present clinical data suggestive of cerebral tumor. It has been accepted that multiple sclerosis failed to show expansive signs in the computerized tomography (CT). However, since 1979 a total number of 13 patients have been reported to have expansive images at the CT. We report 3 cases with clinical symptoms suggesting a cerebral tumor associated with expansive signs at the CT. The subsequent follow-up of these patients confirmed the diagnosis of clinically defined multiple sclerosis. The management of these patients is difficult. Those patients with previous history suggestive of multiple sclerosis should be probably treated with steroids and followed with serial CT. If a clear recovery was not achieved in a relatively short term, a cerebral biopsy is recommended to rule out a neoplasm. When the clinical presentation begins with signs suggestive of a neoplasm, the cerebral biopsy is recommended. PMID- 2261194 TI - [Diagnosis of Moyamoya disease using magnetic resonance]. PMID- 2261195 TI - [Persistent hemifacial contracture and brainstem glioma]. PMID- 2261197 TI - Malignant melanoma in Denmark. Occurrence and risk factors. AB - The age-standardized incidence rate of cutaneous malignant melanoma (CMM) in Denmark increased five- to six-fold between 1943 and 1982. The increased varied by sex and by site, being particularly pronounced for areas of the body normally covered by clothes. A steep increase in risk was revealed for successively younger birth cohorts. Lack of consistency between descriptive epidemiology and indicators for cumulative exposure to sunlight has led to the intermittent exposure hypothesis. Our population-based case-control study, including 474 incident cases of CMM and 926 controls, has further supported this hypothesis and demonstrated that sunbathing is associated with an increased risk of CMM, particularly during childhood and if it leads to sunburning. In addition, the risk of CMM is increased in persons with many pigmented naevi and/or a tendency to freckling. Our study does not support a relationship between CMM and hormonal exposure in women and no association was observed between dietary factors, alcohol intake, tobacco smoking, bathing habits or hair dye use and CMM risk. PMID- 2261196 TI - [The language of doctors]. PMID- 2261198 TI - Colorectal cancer in Sweden. A descriptive epidemiologic study. AB - In a register-based 19-year follow-up we studied the incidence rate of colorectal cancer in the Swedish 1960 census population. A total of 53,377 cases were identified: 28,003 men and 25,374 women. A U-shaped distribution of tumors in the large bowel was observed, with a minimum in the descending colon. Other findings were 1) An incidence gap between elderly men and women increasing with age and with distal direction in the large bowel; 2) An increase in the incidence of colorectal cancer with population density; 3) A higher incidence of colorectal cancer in the southwestern region than in the northern region and 4) A lower incidence of colon cancer among blue than among white collar workers and a lower incidence of colorectal cancer among never married men than among other men. PMID- 2261199 TI - Thyroid carcinoma. A report of 206 cases from an area with endemic goitre. AB - A retrospective analysis of 206 cases of thyroid carcinoma treated at a single surgical service in a region with endemic goitre is presented. In contrast to the marked female preponderance in surgically treated benign thyroid disorders, the frequency of thyroid carcinoma was almost equal in the two sexes (males/females = 100/106). The duration of symptoms was, as a rule, short and there was a predominance of advanced lesions (T3N3M1) even among the well-differentiated tumours. Papillary carcinoma was the most common histologic type (45%) but its proportion was considerably lower than usually reported from non-endemic regions. The average TSH level was significantly elevated in the carcinoma group and associated adenomatous changes were found in 40/100 cases which might suggest an etiologic role of increased TSH stimulation. Since most thyroid carcinomas had a very malignant clinical behaviour, surgical treatment aimed at near-total thyroidectomy which was performed in 62% of the cases. During a follow-up of up to eleven years recurrence in the remaining contralateral lobe occurred in 23% of patients with hemithyroidectomy and loco-regional recurrence was seen in 29% of patients with near-total thyroidectomy. Mortality was high in all histologic types, further underlining the aggressive biologic behaviour of thyroid cancers in an endemic area. PMID- 2261200 TI - Second primary tumors following thyroid cancer. A Swedish record-linkage study. AB - The incidence of second primary tumors was studied through record-linkage in 2,968 thyroid cancer patients reported to the Swedish Cancer Registry during the period 1958-1975. The cohort was matched with the Swedish Cancer Registry between 1959 and 1984. A total of 283 second primary tumors were reported more than one year after thyroid cancer diagnosis, and the standardized incidence ratio (SIR) was 1.18 (95% confidence interval = 1.03-1.31). A significant elevated risk of cancer of the kidney, endocrine glands, and nervous system was noted. Men had a higher risk (SIR = 1.37; 95% CI = 1.06-1.70) than women (SIR = 1.11; 95% CI = 0.96-1.28). Patients who were 36-45 years at the time of the thyroid cancer diagnosis were at highest risk of developing a second primary tumor (SIR = 1.35; 95% CI = 0.99-1.81). Significantly elevated risks were seen 5-9 years after the thyroid cancer diagnosis (SIR = 1.44; 95% CI = 1:14-1.69), and the SIR was close to unity after greater than or equal to 15 years of followup. Previously described elevated risks of subsequent leukemia and breast cancer were not confirmed in this study. Close medical surveillance, thyroid cancer treatment, hereditary factors, and a high frequency of autopsy could all contribute to the elevated risk of a second primary tumor in these patients. PMID- 2261201 TI - Long-term survival after malignant glioma. A clinical and histopathological study on the accuracy of the diagnosis in a population-based cancer register. AB - The Stockholm Regional Cancer Register (SRCR) contains 1,002 patients with malignant glioma reported between 1958 and 1977. A total of 49 patients had a minimum survival time of 4 years and of these 48 were studied in search for histological characteristics that might explain the unexpectedly good prognosis. In only 8 of the 48 patients (17%) could the diagnosis of malignant glioma of high malignancy grade be verified at histopathological reexamination. All 8 were grade III tumors according to WHO and no primary glioblastomas were found. The explanation for the erroneous registration was either incorrect initial pathological diagnosis or incorrect registration. No common morphological features could be found among the correctly registered long-term survivors. Survival data on gliomas based on original histopathological diagnoses derived from information in population-based cancer registers should be cautiously interpreted. Reliable conclusions can only be drawn when such data are supplemented with clinical information and the histopathology is reviewed. PMID- 2261202 TI - Prognostic factors in head and neck non-Hodgkin's lymphoma with special reference to serum lactic dehydrogenase and serum copper. AB - An analysis of prognostic variables was performed in a retrospective study of 121 patients with Ann Arbor stage I-II head and neck non-Hodgkin's lymphoma admitted from 1973 to 1988. The overall actuarial 5-year survival rate was 58.8% and the minimum follow-up 15 months. Nine clinical and laboratory parameters were studied, including serum lactic dehydrogenase (LDH) and serum copper (SCL), and subjected to univariate and multivariate analyses. In univariate analysis, histology and LDH were found to be significant prognostic variables. Evaluation by Cox's multivariate proportional hazard model revealed histology, SCL and sex to be of prognostic significance. PMID- 2261203 TI - Radiation-induced brachial plexus neuropathy in breast cancer patients. AB - The incidence and latency period of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients by a neurological follow-up examination at least 60 months (range 67-130 months) after the primary treatment. All patients were treated primarily with simple mastectomy, axillary nodal sampling and radiotherapy (RT). Postoperatively, pre- and postmenopausal patients were randomly allocated chemotherapy or antiestrogen treatment. All patients were recurrence-free at time of examination. Clinically, 35% (25-47%) of the patients had RBP; 19% (11-29%) had definite RBP, i.e. were physically disabled, and 16% (9 26%) had probable RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-36%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%) of cases assessment of a definite level was not possible. RBP was more common after radiotherapy and chemotherapy (42%) than after radiotherapy alone (26%) but the difference was not statistically significant (p = 0.10). The incidence of definite RBP was significantly higher in the younger age group (p = 0.02). This could be due to more extensive axillary surgery but also to the fact that chemotherapy was given to most premenopausal patients. In most patients with RBP the symptoms began during or immediately after radiotherapy, and were thus without significant latency. Chemotherapy might enhance the radiation-induced effect on nerve tissue, thus diminishing the latency period. Lymphedema was present in 22% (14-32%), especially in the older patients, and not associated with the development of RBP. In conclusion, the damaging effect of RT on peripheral nerve tissue was documented. Since no successful treatment is available, restricted use of RT to the brachial plexus is warranted, especially when administered concomitantly with cytotoxic therapy. PMID- 2261204 TI - Reversible oedema and necrosis after irradiation of the brain. Diagnostic procedures and clinical manifestations. AB - One hundred and twelve patients with primary brain tumour were followed every 3 months during and after brain irradiation and chemotherapy with brain scanning, EEG and neurological examination. Early delayed radiation reactions were seen in 6 patients. The symptoms developed 2-8 months after irradiation and lasted for 2 3 months. Two types of reactions were observed. One mild form appeared after 2-3 months and was characterized by low-attenuated expansive areas within the irradiated volume, without contrast enhancement on CT scan. Severe reactions appeared in some patients after 6 months, with exacerbation of earlier clinical signs and contrast enhancing lesions on CT. Regression of the CT finding was seen after 3 months. Recognition of this syndrome is important, as a new neurosurgical procedure might cause lasting neurological sequelae in patients who otherwise would recover without treatment. PMID- 2261205 TI - Carcinoma of the nasopharynx. The significance of lymphocytic infiltration. AB - From 1974 to 1985, 76 patients with nasopharyngeal carcinoma (NPC) received irradiation with curative intent and 14 with palliative intent in our department. Of the 76 patients, 59 presented with UICC stage IV. The 5-year actuarial survival rate was 41% and the relapse-free survival rate (RFS) 45%. The slides were reviewed according to the World Health Organization (WHO) histologic classification, also taking into account the degree of lymphocytic infiltration according to its Cologne modification. Undifferentiated carcinoma and non keratinizing carcinoma had similar 5-year RFS (47 and 44% respectively). Patients with major lymphocytic infiltration in the tumor presented with younger median age, with smaller primary tumors and with more advanced neck disease than the other patients. There was, however, no obvious association between the degree of lymphatic infiltration in the tumor and the prognosis. Patients with major lymphocytic infiltration had a 5-year RFS of 44%, versus 49% for patients without such infiltration. PMID- 2261206 TI - Carcinoma of the hypopharynx. A retrospective analysis of the treatment results over a 25-year period. AB - One hundred and sixty-two patients treated for hypopharyngeal cancer during the 25-year period 1958-1982 were reviewed retrospectively. Of the 162 patients, 29 received combined treatment with surgery and postoperative irradiation, 106 received radical radiotherapy alone, and 27 palliative radiotherapy. The 5-year survival rate was 28% for the patients treated with combined therapy and 16% for the patients treated with radical radiotherapy. There were no long-term survivors in the palliatively treated group. The major cause of death was tumour (102 patients) while 40 patients died of intercurrent diseases. PMID- 2261207 TI - External beam radiation treatment of urinary bladder carcinoma. An analysis of results in 203 patients. AB - In a retrospective study, 203 patients with cancer of the urinary bladder were analysed concerning treatment outcome, survival and some prognostic factors. Radiotherapy with curative intent and a tumour dose of 66 Gy in 9 weeks with a 3 weeks' pause after 33 Gy was the planned treatment for 155 patients. Preoperative radiotherapy with a tumour dose of 40 Gy in 4 weeks was delivered to 28 patients, 4-6 weeks prior to cystectomy. Twenty patients with advanced disease received palliative radiotherapy with a tumour dose of 30 Gy in 2 weeks. A significant initial response to radiotherapy was obtained in 26.7% of the patients. The actuarial 5-year survival was 24% for patients treated with definitive radiotherapy only. The most important factors associated with survival in this radiotherapy group were stage (T-class), performance status and serum creatinine. Acute side-effects were common and in 18% of the patients deviation from the planned treatment was necessary. PMID- 2261208 TI - Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation. AB - From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Post-operative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2 4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (GI/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery. PMID- 2261209 TI - Plasma pharmacokinetics of Idarubicin and its 13-hydroxymetabolite after intravenous and oral administration under fasting and non-fasting conditions. AB - The plasma pharmacokinetics of Idarubicin and its 13-hydroxy-metabolite have been studied in 10 patients with solid tumours after intravenous and oral administration under fasting and non-fasting conditions in a randomized cross over design. The plasma concentration time curves of Idarubicin after intravenous administration could be described by the open two or three compartment models. No pharmacokinetic modelling of Idarubicin was possible after oral administration. After oral administration of Idarubicin, the amount of intact drug was higher under non-fasting conditions. The extensive and long-lasting appearance of Idarubicinol suggests that this cytotoxic metabolite is of major clinical importance in i.v. and oral therapy with Idarubicin. The pharmacokinetics of Idarubicinol was not affected by food intake. PMID- 2261210 TI - The relationship between changes in tumour volume, tumour cell density and parenchymal cord radius in a human melanoma xenograft exposed to single dose irradiation. AB - A human melanoma xenograft, in which the viable tumour tissue formed cylindrical cuffs around blood vessels, was irradiated with single doses of 7.5 Gy and 15.0 Gy respectively. The nuclear density, the frequency of giant cells and the mean parenchymal cord radius were measured and compared to the tumour growth response. After 7.5 Gy, the growth rate was only slightly reduced and there were no significant changes in the nuclear density or the mean parenchymal cord radius. After 15.0 Gy the mean parenchymal cord radius decreased the first week. This coincided with swelling of endothelial cell nuclei and reduced density of functional capillary-like vessels. Although the number of tumour cells declined, the tumour volume increased the first days after irradiation with 15.0 Gy since the cell density was reduced. PMID- 2261211 TI - Chlorpromazine-induced hypothermia in tumour-bearing mice, acute cytotoxic drug lethality and long-term survival. AB - The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity. PMID- 2261212 TI - Doxorubicin and 5-fluorouracil versus doxorubicin and oral ftorafur in in the treatment of advanced gastric cancer--a phase II and III trial. PMID- 2261213 TI - Metastasizing Sertoli cell tumours of the human testis--a report of two cases and a review of the literature. PMID- 2261214 TI - Pityriasis versicolor confined to the radiation therapy field. PMID- 2261215 TI - Response of medullary thyroid cancer to low-dose alpha-interferon therapy. PMID- 2261216 TI - [Oncologic protocol for solid tumors of the upper aerodigestive tracts. Protocol for collection of computerized data]. AB - We present our method for treatment and follow up in patients with head and neck cancer. We have modified Laennec's Hospital Protocole (Paris), and afterwards we have developed a new computerized database system. PMID- 2261217 TI - [Flow cytometry. Its prognostic value in cancer of the head and neck]. AB - The authors introduce an historical review and technical information on the management of this technique. The current condition of this matter is commented on, with special interest in head and neck tumors. Very few, contradictory papers have been published on laryngeal tumors concerning the prognostic value of aneuploid tumors. PMID- 2261218 TI - [Radiological contributions in perennial rhinitis]. AB - We considered over 500 cases of Perennial Rhinitis (PR). A radiologic study has been performed to determine mucosa alterations. The percentage of allergic PR is found to be of forty-eight percent. Radiologic alteration are found in 43% of non allergic PR. We considered also addition factors such as sex, age, occurrence of asthma and levels of IgE. PMID- 2261219 TI - [Post-adenoidectomy velopharyngeal insufficiency in children with velopalatine clefts]. AB - The influence of adenoidectomy on speech has been well documented, essentially in cleft palate children. A revision of the speech outcome in 7 adenoidectomized cleft palate children reveals 4 cases of deteriorated speech. The need of a preoperative evaluation to look for risk factors is outlined, specially in cases of submucous cleft palate. The evolution of cases with permanent postadenoidectomy velar insufficiency with nasometry, shows increasing severity of nasality . PMID- 2261220 TI - [The inverted ipsilateral reflex: is it an artefact?]. AB - We have studied the characteristics of the inverted reflex obtained by ipsilateral stimulation in nineteen patients. Six of them were affected by perceptual hypoacusis, eleven of those patients had an otosclerosis and two a facial paralysis. The conclusion about our investigation is that in all the cases, it was produced by an artefact and it was not a response from the muscles of the middle ear. PMID- 2261221 TI - [Branemarck bone-anchored implants for the adaptation of conductive hearing aids]. AB - This study presents four cases of bone-anchored implants for hearing aid amplification aids are superior to the classic hearing aids. They are also indicated in a larger number of cases of mixed hearing loss and with an average bone conduction as high as 45 dB. PMID- 2261222 TI - [Pseudosarcoma of the larynx]. AB - Pseudosarcoma of the larynx is a tumor derived as much from connective tissue as from epithelial tissue. There has been much discussion about the malignant nature of the sarcomatous stroma, sometimes considered a benign reaction. However they describe in the literature metastasis cases in which only the sarcomatous element has been demonstrated. We present a case of vocal cord pseudosarcoma in which ten months after performing cordectomy, we can't rule out recurrent disease in spite of the histopathological examination of the cord being negative. PMID- 2261223 TI - [Crocodile tears syndrome]. AB - The syndrome of crocodile tears, or Bogorad's syndrome is a rare complication of the facial paralysis. It's characterized by lachrymation on the same side of the palsy in connection with stimulation of salivation (e.g. when eating). We present a case of Melkersson's syndrome who developed a syndrome of crocodile tears. PMID- 2261224 TI - [Frontal osteoma apropos of a case]. AB - We report a case of frontal sinus osteoma in a 66-year-old woman, with headache and deformation of the upper-inner orbit wall; it was satisfactorily solved by means of osteoplastic technique with the aid of surgical microscope. We emphasize the extrasinusal extension, and specially when the osteoma grows towards the orbit or the endocranium, in order to settle on the surgical technique. PMID- 2261225 TI - [Liposuction as a treatment for Launois Bensaude disease]. AB - Launois Bensaude disease is a widespread symmetrical lipomatosis with a head-neck trunk predominance. Its pathogeny is unknown and its treatment, basically surgical, is aggressive, difficult and even exasperating as a result of the large amount of noticed relapses. PMID- 2261226 TI - [Carcinoma of the laryngeal ventricular saccule as an anatomo-clinical entity]. AB - The relationship between laryngocele and laryngeal carcinoma has already been well established. A distinct entity is the carcinoma arising from the ventricular saccule or a preexisting laryngocele showing a peculiar clinical behavior and pathological features. We present here a case of ventriculosaccular carcinoma of the larynx, discussing the clinical presentation and the immunohistochemical analysis performed using monoclonal antibodies, and the factors which might modulate the aggressiveness of the neoplasm. PMID- 2261227 TI - [Chondrosarcoma of the larynx and laryngectomy. Apropos of 2 cases]. AB - Two malignant tumors of cartilaginous origin are presented. Both demonstrated all histologic criteria of chondrosarcomas. Chondrosarcoma of the larynx seem to arise from hyaline cartilage, being the cricoid the mostly involved cartilage. The growth rate is very low, so that the first symptoms, as hoarseness or dyspnea, may be anodyne. The survival rates are directly related to histological grading. Chondrosarcoma are usually of low-grade malignancy. Local growth is predominant, metastasis has been described for high-grade types. Local recurrence may occur even after years. Surgery is the treatment of choice. PMID- 2261228 TI - [Cavernous hemangioma of the maxillary sinus]. AB - We describe a case of maxillary sinus hemangioma which originated in sinusal mucosa and which extended into the nasal cavity. Clinical and radiologic findings are presented and the literature reviewed. Surgery appears curative in most cases. PMID- 2261229 TI - [Neurological symptoms and etiology of severely retarded children]. AB - I identified forty-three patients with severe retardation aged 6-14 years in a defined community. More than half of the patients (23/43) had spastic tetraplegia and 9 had spastic diplegia. Only one case showed abnormal increase of muscle tone of dyskinetic type. The period when they had got underlying causes of their handicaps was as follows : congenital (acquired intrauterine, including intractable cases) 25, perinatal 6, and after the neonatal period 12. An increased proportion of congenital cases and a decreased proportion of perinatal cases are noted when the data were compared with previous reports. About a half of the total cases could be considered to be caused by preventable diseases such as perinatal anoxia, purulent meningitis, or intracranial hemorrhage due to vitamin K deficiency. PMID- 2261230 TI - [Neuropathological study of severely handicapped children: relationships of cortical and subcortical destructive lesions]. AB - Neuropathological examinations were performed on 30 autopsy cases of severely handicapped children. Among them, 11 cases showed bilateral cerebral destructive lesions. The cerebral lesions were divided into three groups; six cases with dominantly grey matter lesions, three with dominantly white matter lesions and two with combined grey and white matter lesions. The cortical lesions were found in the fronto-parieto-occipital lobes and cingulate gyri, while undersurface of the temporal lobes showed less destruction. The white matter lesions, consisting of marked gliosis and atrophy accompanied by ventricular dilatation, were remarkable in the area extending from the periventricular region to the centrum semiovale. These changes were more apparent in the occipital lobes. Cerebellar lesions were found in nine cases, which also were classified into grey matter and white matter lesions. The extent and characteristics of these lesions resembled those of the cerebral lesions. The basal ganglia showed no remarkable destruction in the cases with severe cortical and subcortical damages. It was assumed that these nuclei had survived the disconnection from the cortex. Thalamic lesions were observed in six cases, mainly restricted to the dorsal and/or lateral nuclei. No relationship was found between these thalamic lesions and the extent or intensity of cerebral destruction. It is suggested that each of the thalamic nuclei has a different characteristic vulnerability to such destructive conditions. PMID- 2261231 TI - [A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. II. Analysis of brain metabolism using 31P- and 1H-nuclear magnetic resonance spectroscopy]. AB - We studied the brain metabolism in macular mutant mice (Ml/y, +/y), an appropriate model of Menkes kinky hair disease, using 31P- and 1H-NMR spectroscopy to clarify the pathophysiological mechanisms of disturbed nervous function. An analysis of in vivo 31P-NMR spectra showed a decreased phosphocreatine (PCr)/inorganic phosphate (Pi) ratio and decreased ATP levels and decreased intracellular pH in Ml/y mice at 9 days, suggesting energy failure in the brain. This associated decline in ATP levels may reflect multiple causative factors including disturbed mitochondrial respiration and ischemia secondary to circulatory failure. Brain metabolites, including PCr, creatine, lactate and 7 amino acids were easily detectable quantitatively and qualitatively by in vitro 1H-NMR spectrum. An elevation in lactate levels and a decline in PCr/creatine ratio in Ml/y mice at 9 days were also noted with an in vitro study, supporting the in vivo data. NMR spectroscopy is a useful and promising tool to obtain the information on brain metabolism. PMID- 2261232 TI - [A power spectral analysis of the EEG in the newborns. I. Developmental changes of normal babies]. AB - Power spectral analysis of the EEG at the neonatal period was performed in 50 premature babies and 36 mature babies. The gestational age ranged from 26 to 40 weeks, and birth weight from 762 g to 3,232 g. All EEGs were recorded when the babies reached to 37-41 weeks of conceptional age, and analyzed using fast Fourier transformation. The relative power in active sleep was evaluated in this study. The percent power of the delta 1 band ranging from 0.5 to 2.0 Hz decreased immediately with increasing conceptional age, while that of the delta 2 (2.2-3.8 Hz), theta 1 (4.0-5.4 Hz) and theta 2 (5.6-7.8) increased with conceptional age. However, no significant change was recognized in the alpha (8.0-12.8 Hz) and beta 13.0-29.8 Hz). These results suggest that the development of the EEG depends on the post conceptional age. The percent power of delta 1 to beta bands was compared among the frontal, central, parietal and occipital regions. The development of EEG in the central region was prominent among other 3 regions in EEG development. The EEGs of premature babies were compared to those of mature babies at the same conceptional age. The percent power of premature babies was higher at the delta 1 band, whereas lower at the delta 2, theta 1 and theta 2 bands than that of mature babies. The data showed that premature babies were more immature than age-matched mature babies in the development of EEGs. PMID- 2261233 TI - [A power spectral analysis of the EEG in the newborns. II. The power spectral changes of the infants with neonatal asphyxia]. AB - Power spectral analysis of the EEG at the neonatal period was performed in 33 babies with an Apgar score of 6 or less 1 minute after delivery. Their gestational ages ranged from 27 to 40 weeks, and birth weight from 1,013 g to 4,416 g. They were followed up until 18 months of age. All EEGs were recorded when the babies reached to 37-41 weeks of conceptional age, and analyzed using fast Fourier transformation. The percent power in active sleep was evaluated in this study. The abnormal EEG patterns in infants with neurological damage was classified into the following groups: (1) Increase of the percent power of the delta 1 band, (2) Decrease of the percent of the power of the delta 1. On the other hand, the EEG patterns at the neonatal period in infants with normal development who suffered from neonatal asphyxia were similar to those of age matched controls. These results suggest one of the most important factors deciding the prognosis of the brain damage is the presence of a normal percent pattern. In conclusion, power spectral analysis of EEG at the neonatal period is useful in predicting the outcome of brain damage if it is used with visual inspection. PMID- 2261234 TI - [Benign familial neonatal convulsion: clinical features of the propositus and comparison with the previously reported cases]. AB - A patient with benign familial neonatal convulsions was presented. The patient had the first episode of cyanosis on the second day of life. Thereafter, he also experienced focal clonic and/or multifocal clonic seizures. The interictal EEG showed no definite abnormality. Between the seizures he appeared well and physical examination was essentially normal. Treatment with phenobarbital (4 mg/kg/day, P. O.) was started and subsequently he had no further seizures until 3 months. At the age of 4 months, he was admitted to the hospital again because of generalized tonic-clonic seizures. The interictal EEG showed sporadic spikes dominantly in the right central area. The findings of ictal EEG at that time are characterized by fast spiking of increasing amplitude during the tonic phase. During the clonic phase, there are repetitive+ bursts of spikes and sharps mixed with persisting muscle potential. The termination of the convulsion is characterized by general voltage depression. Clinical characteristics such as seizure types, EEG findings, responses to antiepileptic drugs and recurrence of the seizures found in our propositus were compared with those of the patients previously reported in the literature. PMID- 2261235 TI - [The relationship between severity of spastic diplegia and laterality of the cerebral function]. AB - Seventeen children with clinical evidences of preterm birth and spastic diplegia (SD) were studied about the relationship between clinical severity and laterality of cerebral function. The result showed the patients with the left-handed SD were more serious than those with the right-handed in their intelligence and activity of daily living. As the severity increased, motor difficulty was also observed at upper limbs, and especially spasticity was detected at the right hand. The dichotic listening test showed the right ear dominance only in the patients with the right-handed SD. MRI examination was performed in 10 cases, and periventricular leukomalacia (PVL) was detected in all cases. There was few correlation between PVL and clinical laterality. We speculated that right-hand spasticity which was seen in severe cases was due to the fragility of periventricular structure in the left hemisphere. PMID- 2261236 TI - [Alzheimer's neurofibrillary tangles in a 52-year-old patient with severe brain damage]. AB - A woman, who had been developmentally delayed since her birth, further deteriorated after she got an episode of high fever of unknown origin at 2 years of age. At the age of 52 years, she died of liver cancer after a long-standing HB virus carrier state. Neuropathological examination revealed brain atrophy, narrowed white matter, myelin pallor, fibrillary gliosis and status marmoratus of the thalamus. These findings suggested the primary cause of the brain pathology in this case to be a developmental destructive process which should have taken place in the early stage of brain development. In addition, neurofibrillary tangles (NFT) were noticed in the hippocampus, locus ceruleus and nucleus basalis of Meynert, but no senile plaques were found anywhere. These NFT changes seemed to be closely resembling to those of the Fukuyama type congenital muscular dystrophy. But the reason why NFT occur in this case is still obscure and probably different from that in the Down syndrome or in physiological senility. PMID- 2261237 TI - [Cerebrospinal fluid biopterin in Rett syndrome]. PMID- 2261238 TI - European Charter on Environment and Health. PMID- 2261239 TI - A broadly-based training in toxicology? PMID- 2261240 TI - Anticholinesterase poisoning in Turkey--clinical, laboratory and radiologic evaluation of 269 cases. AB - A retrospective study was conducted on 269 patients with anticholinesterase poisoning who had been admitted to the Internal Medicine and Pediatric Clinics over the past 10 years. Their ages ranged from 17 d to 62 years. In adults, suicide was the most common means of intoxication. Miosis was the most frequent symptom and was seen in 80.66% of the patients. Hyperglycaemia, hypoglycaemia, hypokalaemia, hyperkalaemia, hyperchloraemia, hypochloraemia and hyponatraemia were among the electrolytic and haematologic disorders (hyperglycaemia 48.00%, hypoglycaemia 6.40%). There were also electrocardiographic abnormalities. Asthma, although usually a late complication, was also noted at the beginning of treatment. Mortality rates were 8.98% for children and 9.6% for adults. Since hypoglycaemia was found in all the patients who died, it was accepted as an ominous prognostic sign. We think that anticholinesterase poisoning is an important health problem in our country. It is much less common in developed than semi-developed countries, and a complete understanding of it is essential for the emergency physician. PMID- 2261241 TI - Vitamin E and selenium in gentamicin nephrotoxicity. AB - 1. The sequence of renal cellular membrane damage induced by gentamicin was studied in the rat by using the release of alkaline phosphatase, acid phosphatase, muramidase and protein from renal cells as indices of renal damage. 2. The protective effect of a combination of vitamin E and selenium against renal damage was also investigated. 3. Gentamicin (60 mg kg-1 body weight) was nephrotoxic within 12 h of the first dose. 4. The plasma membrane of the renal tubules is damaged before the lysosomal membrane is affected. 5. A combination of vitamin E (1 mg g-1 body weight) and selenium (4 x 10(-3) mg g-1 body weight) attenuates the renal damage induced by gentamicin. Results suggest synergism between vitamin E and selenium in attenuating the renal damage. The possible mechanism of attenuation is discussed. 6. Vitamin E and selenium may have anti diuretic potential. PMID- 2261242 TI - The effect of the alpha-particle emitter astatine-211 in the mouse at the minimum toxic dose. AB - The radioactive halogen astatine-211 was injected into mice in an amount producing minimal toxicity. Histopathological examination of tissues at intervals between 3 d and 16 weeks showed the following changes: 1. Radiation-induced necrosis and progressive fibrosis of the thyroid gland. The gland was reduced to 25% of its original mass with only a few relatively normal follicles persisting. 2. A small, temporary, reduction in peripheral blood lymphocytes, platelets and red cells and a significant persistant increase in polymorphs. 3. Severe reduction in reproductive cells in the testis with some signs of recovery at 16 weeks. PMID- 2261243 TI - Biological effects of inhaled 239PuO2 in rats with pre-existing pulmonary emphysema. AB - The modifying effects of pre-existing pulmonary emphysema on the deposition, distribution, retention and effects of inhaled 239PuO2 in the rat were investigated. The presence of emphysema in the rats was documented by morphometric and respiratory function measurements. For rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kg body mass were lower in rats with emphysema than in those without emphysema; however, the retention of 239Pu over time was similar in both groups. The distribution of 239Pu particles in the lungs of rats with emphysema tended to be more random than in the lungs of control rats. The life span, and incidences of non-neoplastic and neoplastic lesions in the lung, and risk of lung tumours per unit of alpha dose to the lungs in the rats with emphysema were similar to or less than in the control rats, when groups with similar initial lung burdens of 239Pu were compared. The results of this study suggest that humans with uncomplicated pulmonary emphysema are not necessarily more sensitive to the carcinogenic effects of inhaled 239PuO2 than individuals with normal lungs. PMID- 2261244 TI - Pharmacokinetics and toxic effects of nifedipine in massive overdose. AB - A 57-year-old man took 30 x 20 mg nifedipine retarded release tablets. He developed hypotension, tachycardia and flushing, but remained in sinus rhythm. The concentration of nifedipine 10 h after overdose was 604 micrograms 1-1, and of the M-I metabolite 110 micrograms 1-1. Log concentration time curves were linear from 10-72 h for nifedipine, with a half-life of 7.5 h; and for M-I with a half-life of 8.2 h. On this evidence, oral absorption of nifedipine retarded release is complete by 10 h. There was no evidence of saturation of nifedipine or M-I metabolism, even at concentrations ten times above the therapeutic concentration. PMID- 2261245 TI - EEG appearances in acute carbamazepine toxicity. AB - A 16-year-old woman deliberately took a large, toxic overdose of carbamazepine and recovered despite a high plasma level. During the acute phase the EEG was dominated by occipital delta activity suggestive of a brainstem disorder. Following 24-h treatment with activated charcoal the plasma carbamazepine was cleared and the EEG returned to normal. PMID- 2261246 TI - Morphine-6-glucuronide might mediate the prolonged opioid effect of morphine in acute renal failure. AB - 1. A 43-year-old male developed acute kidney failure due to ethylene glycol poisoning. He was treated with bicarbonate to combat metabolic acidosis, ethanol as an antimetabolite and haemodialysis to remove the glycol and its toxic metabolites. He was kept on a respirator and sedated with morphine. Peritoneal dialysis was given for 36 d. Following sedation with morphine for 11 d, the patient was given naloxone and then extubated. The antidote had to be continued for 14 d to prevent respiratory depression, until kidney function improved. 2. Only morphine-6-glucuronide (M-6-G) was found in the plasma and CSF at concentrations which might explain the opioid effects observed in the patient during the days after the cessation of morphine treatment. The ratio of the area under the concentration-time curve (AUC) of morphine-3-glucuronide (M-3-G) to M-6 G was 2:1. The elimination half-lives of M-3-G and M-6-G were 55 and 82 h, respectively. The clearance data indicate that most of the glucuronides were eliminated by peritoneal dialysis during renal failure. 3. The data suggest that M-6-G exerts opioid effects and is retained in acute kidney failure. Morphine should therefore not be used preferentially as a sedative/analgesic in pronounced kidney failure. PMID- 2261247 TI - [Results of the use of a graft with a monocusp in radical correction of Fallot's tetrad]. AB - The article deals with the results of complex study of the effect of pulmonary insufficiency on intracardiac hemodynamics and function of the heart in the immediate and late-term periods after radical correction of Fallot's tetralogy. Answers are also given to questions concerning the expediency of the use and functional adequacy of a xeno-pericardial monocusp in the closure mechanism of the pulmonary artery valve. The study showed that massive pulmonary regurgitation has a negative effect on the functional condition of the right ventricle in late term postoperative periods. Convincing data were obtained which allow a graft with a monocusp of a bull's pericardium to be recommended for further clinical use to prevent insufficiency of the pulmonary artery valve after radical correction of Fallot's tetralogy. PMID- 2261248 TI - [Hemodynamic evaluation of the effectiveness of preservation of subvalvular structures in mitral valve prosthesis]. AB - The article deals with the clinical evaluation of the results of mitral valve prosthetics with preservation of the subvalvular structures in 40 patients and comparative evaluation of the hemodynamic indices after prosthetics with preservation of the subvalvular structures of the posterior cusp and after routine mitral valve prosthetics. The authors show good clinical results in patients after valvar-preserving prosthetics of the mitral valve and essential improvement of left-ventricular contractile activity after such an operation. Comparative analysis showed that the total ejection fraction increased by 10.8 +/ 4.5% in the main group and reduced by 11.4 +/- 2.6% (p less than 0.01) in the control group. Left-ventricular end diastolic pressure did not change in the main group but increased significantly (p less than 0.05) in the control group. A conclusion is drawn that preservation of the subvalvular structures in mitral valve prosthetics is expedient even in patients with an initially grave condition because the method makes it possible to normalize intracardiac hemodynamics more rapidly in the postoperative period and essentially improve the contractility of the left ventricle. PMID- 2261249 TI - [Changes in cardiac hemodynamics, volume and pumping function of the heart ventricles in natural course of Fallot's tetrad]. AB - The work analyses the results of repeated clinical and intracardiac examination of 13 patients with tetralogy of Fallot, conducted at the age of 23.1 +/- 9.9 and 42.3 +/- 13.1 months. The severity of the clinical condition grew markedly during natural course of tetralogy of Fallot (TF): the SaO2 value reduced from 71.8 +/- 7.2 to 65.0 +/- 8.0% and the blood hemoglobin level grew from 165 +/- 28 to 194 +/- 30 g/l. The data presented are evidence that in TF following a natural course a distinct tendency is displayed to growth of end diastolic volume of both ventricles in relation to the normal value and their dysfunction progresses in the form of reduction of the ejection fraction and increase of right-ventricular diastolic "rigidity". The results of the present work may be considered a substantiation of the tactics of early TF correction in infants and young children before the development of serious morphological changes and functional disorders. PMID- 2261250 TI - [Intravascular radiologically-guided surgery in the treatment of congenital heart defects]. AB - The article discusses the experience of the Bakulev Institute of Cardiovascular Surgery, USSR AMS, in catheter endovascular radiologically-guided surgery of some congenital heart diseases in the period from 1967 to 1990. A total of 505 operations were performed at the department of radiologically-guided examination and treatment of the heart and vessels: 307 Rashkind's and 35 Park's operations in total transposition of the great vessels, 110 balloon dilatations in valvular stenosis of the pulmonary trunk and 13 in valvular stenosis of the aorta, 7 embolizations in coronary-cardiac fistulas, 2 balloon dilatations in constrictions of Blalock-Taussig anastomosis, 14 balloon dilatations in peripheral stenoses of the pulmonary arteries, etc. The methodical aspects and the results of endovascular interventions are discussed in detail. The data of foreign researchers on the promising methods of radiologically-guided surgery are also shown. PMID- 2261251 TI - [Complications after implantation of anti-embolic cava filter]. AB - The article is based on study of the immediate results of REPTELA cava-filter implantation in 750 patients and the late-term results in 400 patients. The incidence of the complications is low. Hematoma at the site of subclavian vein puncture developed in 1.6%, retroperitoneal hematomas in 0.1%, migration of the cava-filter occurred in 0.9% of cases. The main causes of the complications are linked with improper methods of implantation of the cava-filter. PMID- 2261252 TI - [Vein grafts in situ in surgery of atherosclerotic lesions of the arteries of the lower limbs]. AB - Reconstructive operations with the use of autologous veins were carried out on 154 patients with occlusive lesions in the femoropopliteal and femorotibial segments. Reversed autologous vein was used to form a shunt in 109 patients and autologous vein in situ in 45 patients. Patency of the shunts, both in the immediate and late-term periods, was higher in the in situ techniques than in the group with a reversed vein (93.3 and 88.8%; 78.9 and 72.4%, respectively). With the use of micro-surgical techniques the number of good results increased by 20.4%. In successful reconstructions in both groups the malleolobrachial index increased from 0.27 +/- 0.02 to 1.03 +/- 0.15. There were no statistically significant differences in the values of the malleolobrachial index in patients of both groups with functioning shunts in the late-term period (of up to 2 years). PMID- 2261253 TI - [Use of therapeutic plasmapheresis in heart surgery patients with hepatic insufficiency]. AB - Therapeutic plasmapheresis is a highly effective method in the preparation of patients with hepatic insufficiency for operation on the heart under conditions of extracorporeal circulation. It leads to reduction of the bilirubin level and normalization of the main values of hepatic function. The positive effect of therapeutic plasmapheresis is less manifest in acute hepatorenal insufficiency developing after operation with extracorporeal circulation. The best effect of therapeutic plasmapheresis in the postoperative period was produced in patients in whom hemorrhages and the low cardiac output syndrome were removed. PMID- 2261254 TI - [Significance of the arrest of pulmonary circulation in the genesis of postperfusion pulmonary complications in open heart surgery]. AB - The purpose of the work is to elucidate the importance of pulmonary circulation arrest during extracorporeal circulation in the development of microcirculatory disorders in the pulmonary tissue. Experiments showed that temporary arrest of pulmonary circulation under conditions of extracorporeal circulation is attended by the development of ischemia of the respiratory pulmonary tissue. The systemic blood flow in the arterio-arterial anastomoses between the pulmonary and bronchial arteries is incapable of providing the pulmonary tissue with blood. Ischemia of the parenchyma leads to disorders in the microvessels of the organ, the manifestation of which in the ischemic and postischemic, periods is determined by the duration of the pathologic effect. The data gained indicate the importance of developing methods for the prevention and treatment of ischemic and postischemic pulmonary microcirculatory disorders and determining the safe terms of pulmonary artery ischemia. PMID- 2261255 TI - [Hemorheology and blood thrombotic potential in pulmonary thromboembolism]. AB - Examination of 138 patients with acute venous thrombosis of the lower limbs, which was complicated by thromboembolism of the pulmonary artery in 49 of them, showed the rheologic status to be disturbed to a greater extent in patients with pulmonary embolism than in those with acute venous thrombosis. An interrelationship between the rheologic properties and the coagulation system of the blood in various conditions of the hemostasis system was revealed. It is pointed out that pathogenetically grounded correction of the disorders of the blood coagulation and rheologic systems is necessary in choosing the method for treatment and prevention of acute venous thrombosis and pulmonary embolism. PMID- 2261256 TI - [Possibilities of ultrasonic dopplerography and multi-level manometry in the evaluation of lesions of the arteries of the lower limbs]. AB - Dopplerographic and manometric examination was conducted in 429 patients with obliterating lesions of the lower limb arteries in order to find optimal diagnostic combinations. The data of noninvasive diagnosis were verified in 119 cases. The data obtained bore evidence that coincidence of the findings of ultrasonic dopplerography and multilayer manometry is indicative, with a high degree of probability, of the presence or absence of lesions of the lower limbs. The findings of ultrasonic dopplerography are the main criteria in appraising affections of the aortoiliac segment and those of multilayer manometry--in appraising affections of the femoropopliteal segment. The findings of both methods are of equal significance in appraising the tibial segment. Multilayer manometry allows indirect appraisal of the condition of arteries in the channel of the deep femoral artery. PMID- 2261257 TI - [Clinico-morphological bases of the choice of surgical method in echinococcosis of the organs of the thoracic cavity]. AB - The article deals with the treatment of 831 patients with echinococcosis of the lungs. It gives a clinico-morphological substantiation of surgical interventions in various conditions of the hydatid and in bilateral and multiple affection. Combined involvement of the heart, diaphragm, pleura is a casuistry. PMID- 2261258 TI - [Treatment of multiple and associated bilateral echinococcosis of the lungs and liver]. AB - The peculiarities of one-stage echinococcotomy in 7 patients with multiple and combined bilateral echinococcosis of the lungs and liver are discussed. The operation is carried out by two surgical teams who work simultaneously except for the interval of time from the moment that the pleural cavity is opened to the removal of the pneumothorax, in which period the surgeons work in turns. PMID- 2261259 TI - [Surgical treatment of pulmonary echinococcosis]. AB - Operation with the use of a laser for resection of the external fibrous capsule with re-expansion of the remaining cavity in patients with echinococcosis of the lungs is more effective than operation by capitonnage of the cavity. The main advantages of laser operations were the absence of closed cavities, deformities of bronchi, atelectasic areas of tissue around the fibrous cavity, and disorders of capillary blood flow and bronchial patency. All this allowed poor results of the operation and fatal outcomes in the main group of patients to be avoided. PMID- 2261260 TI - [Use of polymer hemostatic cotton and plate in surgery of the lungs and pleura]. AB - The article discusses the efficacy of using polymeric hemostatic wool and plate in operations on the lungs and pleura in experiments. From the results of experimental studies the authors concluded that a biodegradable polyamide based on hexamethylenediamine and derivatives of amino acids in a model of parenchymatous-capillary bleeding from the lungs and pleura is an effective hemostatic. The authors recommend these polymers for use in the clinic. PMID- 2261261 TI - [Unfavorable outcomes and complications of temporary occlusion of the bronchi]. AB - The authors possess experience in applying temporary bronchial occlusion (TBO) in 184 patients in whom the procedure was conducted 236 times. The outcomes of TBO were poor in 17.3% (32) of cases and complications occurred in 8.1% (15) of cases. The poor outcomes were due to ungrounded increase of the indications for the performance of TBO. Complications can be brought to minimum if TBO is conducted in specialized departments by experienced endoscopists-bronchologists. PMID- 2261262 TI - [Possibilities of the assessment of the level and degree of bronchial patency according to the data of a flow-volume loop in patients who underwent lung surgery]. AB - On the basis of examination of 45 patients who had been operated on for tuberculoma, tumors, abscesses, echinococcosis, developmental anomalies of the lungs and bronchiectasis it is concluded that R. F. Klement's tables of the degrees of bronchial patency gradation for phthisiopulmonological patients cannot be used for characterizing bronchial patency in individuals who had undergone operation. The dependence of some indices of the flow-volume loop on the volume of the resected lung is shown. The authors claim that in order to use the above mentioned tables in characterizing the degree of bronchial patency in patients subjected to operation, a conversion factor must be elaborated. PMID- 2261263 TI - [Endoscopic study using a superthin endoscope in benign esophageal strictures]. AB - To increase the diagnostic possibilities, the authors suggested a method of endoscopic examination of patients with esophageal strictures by means of a superthin PF-28 fibroscope produced by the Olympus firm (Japan), which was introduced along a string-guide. The examination was successful in 24 of 26 patients. Clinical observations have shown that esophagogastroscopy with a superthin endoscope makes it possible to recognize the exact length of the stenosed segment, detect the second zone of stenosis, and determine the condition of the mucous membrane of the esophago-gastric junction and the proximal part of the stomach. PMID- 2261264 TI - [Benign neoplasms of the mediastinum]. AB - The authors discuss the results of surgical treatment of 105 patients with benign neoplasms of the mediastinum. Cysts were encountered in 22.9% and benign tumors in 77.1% of cases. Two complications occurred during the operation: injury inflicted to the intercostal artery in removal of a neurofibroma and injury to the lung in removal of a mediastinal cyst. The authors conclude that surgery of mediastinal neoplasms is a radical method of treatment. PMID- 2261265 TI - [Surgical treatment of patients with cancer of the cardio-esophageal region]. PMID- 2261266 TI - [Successful treatment of acute endocarditis of the mitral and aortic heart valves complicated by abscess of the aortic root, aneurysm of the ascending aorta and abscess of the spleen]. PMID- 2261267 TI - [Surgical correction of aneurysm of the thoracic aorta and aortic insufficiency in children]. PMID- 2261268 TI - [A rare case of substernal goiter]. PMID- 2261269 TI - 'Reduced funding affects dental schools'. PMID- 2261270 TI - Lessons to learn. PMID- 2261271 TI - 'Survey of general anaesthesia and sedation in dental practice in two cities'. PMID- 2261272 TI - 'Surgeons fear threat of AIDS in the air'. PMID- 2261273 TI - 'Internal' preparations under the GDS. PMID- 2261274 TI - 'The yankee dodge'. PMID- 2261275 TI - Allergic reactions to powders used in latex gloves. PMID- 2261276 TI - Maxillary 4th and 5th molars. PMID- 2261277 TI - The use of rubber dam in the UK. A survey. AB - The purpose of this survey was to determine the frequency of use of rubber dam isolation in the United Kingdom for both operative and endodontic procedures. Questionnaires were sent to 1800 dentists throughout the country, with 1008 returns (56%). Most replies were from dentists active in general dental practice. The use of rubber dam is largely neglected and more than 70% of all dentists surveyed did not utilise rubber dam for any procedure whatsoever. PMID- 2261278 TI - Short root anomaly. AB - A case of generalised short root anomaly is described. All permanent teeth had abnormally short roots, associated with microdontia, hypodontia and a dens invaginatus. Members of the patient's family were similarly affected. PMID- 2261279 TI - Accidental application of cyanoacrylate to the mouth. AB - Accidental application of cyanoacrylate adhesives to the eye and ear occurs not infrequently. A case is reported of inadvertent application of such an adhesive to the mouth. This could conceivably have given rise to respiratory embarrassment. The management of the patient is discussed, since such an incident potentially provides an instant, accurately fitting mechanical obstruction which can compromise respiratory function. Clearly the management must be rapid, and it may prove difficult to treat respiratory obstruction caused in this way. PMID- 2261280 TI - Recognition of oral lesions of HIV infection. 1. Candidosis. AB - Oral problems are often the first significant clinical manifestations of infection with human immunodeficiency virus (HIV). Their early recognition affords the best opportunity for effective therapeutic intervention of HIV infection and opportunistic infections, as well as for oral health education in order to avoid future problems. This also provides optimal time for behaviour modification and coming to terms with the psychosocial consequences of HIV disease. This series of three articles presents a pictorial review and update on the oral manifestations of HIV infection. PMID- 2261281 TI - Keeping your staff. Part 1. A table clinic. AB - Staff problems are all too frequent, and be it losing them, replacing them or training them it can be a costly and frustrating business. At the 1990 BDA International Congress, Charles Scola presented a table clinic addressing exactly these problems. In the first of this two part article he considers just how you can 'keep your staff'. PMID- 2261282 TI - Project teeth relief: dental aid for rural Zambia. AB - For 10 weeks, at the end of last year, my wife and I went out to Zambia with Project Teeth Relief, a UK based charity providing dental care to the rural areas of Zambia. The aim of the charity is to provide emergency dental care, dental health education and training for local health workers in the rural areas where there are no dental services available. Dentists on long-term contracts and volunteers who will spend 2-3 months at a time in the rural area are needed urgently to go out to the country. PMID- 2261283 TI - The BDA Museum: looking to the future. AB - Last year, 1989, was Museums' Year, a year intended to promote a more positive image for museums and galleries, including the British Dental Association's own museum. But how many readers are aware of the background to the BDA museum and the effort that goes into providing this valuable record of dental history? PMID- 2261284 TI - Delineation of gliomas with magnetic resonance imaging using Gd-DTPA in comparison with computed tomography and positron emission tomography. AB - Fourteen patients with cerebral gliomas were investigated by MR imaging using Gd DTPA (Magnevist), CT with the contrast agent iohexol (Omnipaque) and, as a reference, positron emission tomography (PET) using 11C-L-methionine. Tumour areas with disruption of the blood-brain-barrier (BBB) as seen on MR and CT were compared with areas increased accumulation of methionine in PET. There were 6 patients with high-grade astrocytoma (grade III-IV), 5 with low-grade astrocytoma (grade I-II) and 3 with oligodendroglioma. In 4 high-grade tumours, PET showed a larger tumour or tumour tissue in additional areas, compared with enhancement on MR and CT, while in 2 cases the tumour extension was similar in the three modalities. In the low grade tumour group, the findings on PET differed from those on post-contrast MR or CT in 7 cases. In 3 of these cases, no disruption of the BBB was seen either on MR or on CT. In 2 of our 14 patients CT showed larger enhancement extension than MR and in 2 cases MR was superior to CT in this respect. The enhancement intensity was higher on MR in 4 patients and on CT in 2 patients. No definite difference in the delineation of tumour tissue between the T1 weighted SE sequences was found. The gradient echo sequences FLASH and FISP gave limited information that was less than that provided by the T1 weighted SE sequences. A greater increase in signal intensity in T1 weighted images was usually seen 5 min post-contrast in the high-grade tumours than in the low-grade ones. PMID- 2261285 TI - Mass effect and atrophy after stroke. AB - Cerebral edema, resolution of edema, and subsequent development of cerebral atrophy were studied prospectively in 83 patients with ischemic stroke with CT 3 days, 2 weeks, and 6 months post-stroke. Nineteen patients had large (diameter greater than 3 cm), 25 medium sized (diameter greater than or equal to 1.5 less than or equal to 3 cm), and 15 lacunar infarcts (diameter less than 1.5 cm). In 24 patients no infarcts were seen. Changes of Evans' ratio (ER), septum-caudate distance (S/C), and width of widest cortical sulci (SuW) were taken as markers of mass effect/atrophy. These parameters were within normal limits in most cases. However, when all CT scans performed in each patient were compared, changes of ER, S/C, and SuW became apparent as evidence of mass effect and subsequent atrophy development. Mass effect occurred in 81 percent and atrophy in 58 percent of patients with large infarcts. In patients with medium sized infarcts, mass effect occurred in 38 percent and atrophy in 45 percent. PMID- 2261286 TI - Anatomic variations of the cochlea and relations to other temporal bone structures. AB - A thorough knowledge of the normal range of variation of anatomy and topography of the cochlea is necessary for optimal reproduction of this structure and correct interpretation of the radiographs. Radiographic identification of incomplete cochlear coils is essential in the diagnosis of congenital malformations such as Modini's deformity. Furthermore, a diagnosis of otosclerosis/otospongiosis has to be based on recognition of changes in the otic capsule. The size and shape of the human cochlea and the normal ranges of variation of its dimensions were evaluated in 95 plastic casts, prepared from temporal bone specimens. The normal range of variation is fairly small, and is not age-dependent. Obvious digression from this range, associated with pertinent clinical symptoms, indicates an abnormality. PMID- 2261287 TI - Prolonged T1 relaxation of the hemopoietic bone marrow in patients with chronic leukemia. AB - Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior iliac crest (within 72 hours of the MR examination) in order to provide data on bone marrow cellularity and differential counts. The patients with chronic leukemia all showed a significant prolongation of the T1 relaxation times compared with the normal range for hemopoietic bone marrow. PMID- 2261288 TI - Isthmic lumbar spondylolisthesis with sciatica. MR imaging vs myelography. AB - Seventeen patients with sciatica and isthmic lumbar spondylolisthesis were studied with magnetic resonance (MR) imaging. In 13, myelography was also performed: 5 had dural sac deformation and root sleeve shortening, 2 had deformation with unilateral root sleeve shortening, one had bilateral root sleeve shortening only, and one had sac deformation only. In 4, myelography was normal. On sagittal MR examinations the neural foramen had an altered shape bilaterally with the long axis horizontal in all cases. In addition to altered shape the following was found in the 33 foramina evaluated. I: normal nerve (n = 8); II: compressed nerve (n = 16); III: disappearance of fat, nerve not possible to identify (n = 9). In patients with unilateral sciatica, the degree of foraminal stenosis correlated well with the side of symptoms. Coronal views showed the course of the nerve and pedicular kinking. Eight patients underwent decompressive surgery which revealed nerve compression by hypertrophic fibrous tissue and pedicular kinking, which correlated well with the findings on MR. Since the site of nerve compression often was peripheral to the root sleeves, myelography did not give complete information. PMID- 2261289 TI - MR imaging of experimental intramuscular hemorrhage at 0.02 T. Contrast enhancement with Gd-DOTA. AB - Intramuscular hemorrhage was induced by injecting autologous blood into the paraspinal muscle of 8 rabbits. In order to evaluate the time-dependent changes of hemorrhage observed on MRI, the animals were imaged at different stages of blood resolution at 0.02 tesla (T), and control examined with ultrasound using a 7.5 MHz linear transducer. Six inversion recovery sequences (TR = 1,000 ms. TE = 30 ms, and TI = 18, 48, 148, 201, 302, and 398 ms) were used for the in vivo calculation of T1 relaxation times. IR 1,000 (398)/30 imaging was performed before and after the Gd-DOTA administration. The hemorrhage was evident on MR images throughout the study, especially on the T2 weighted (SE 1,000/100) images. MRI showed the healing lesion longer than ultrasound. The T1 relaxation time increased during the time of resolution. Lesions on days 4 to 7 enhanced in intensity after the injection of Gd-DOTA. PMID- 2261290 TI - Radiography of the wrist. A new device for standardized radiographs. AB - A number of methods exist for determination of carpal bone angles on lateral wrist radiographs. However, there is no general or precise definition of the angles measured. In this study the positioning of the wrist is emphasized and a device used to obtain standardized radiographs is presented. An analysis of variance of two series of patients revealed no radiological difference between the contralateral wrists in the same person. We conclude that the asymptomatic wrist can be used as normal reference in the assessment of carpal bone angles in the pathological wrist and a difference between the carpal bone angles in the two wrists in the same person exceeding 5 degrees can be considered significant. PMID- 2261292 TI - Assessment of congestive heart failure in chest radiographs. Observer performance with two common film-screen systems. AB - The effect of observer variations and film-screen quality on the diagnosis of congestive heart failure based on chest radiographs was studied in 27 patients. For each patient, two films were exposed, one with the Kodak Lanex Medium system and one with the Agfa MR 400 system. The films were presented to three observers who assessed the presence of congestive heart failure on a three-graded scale. The results showed no significant difference between the two systems but large systematic differences between the observers. There were also differences between the two ratings by the same observer that could not be explained by the film screen factor. It is concluded that the choice between these two systems is of little importance in view of the interobserver and intraobserver variability that can exist within the same department. PMID- 2261291 TI - Thallium-201 single photon emission computed tomography in patients with symptoms of heart disease and non-significant coronary artery lesions. AB - Polar presentations of coronary angiograms and myocardial 201Tl SPECT were compared in 44 patients without significant coronary artery disease (less than 50% stenosis at angiography). Regions of reduced isotope activity (defects) were present in 18 patients (41%). Nine of these had angiographic and/or clinical evidence of non-coronary heart disease, such as documented or suspected myocardial infarction, dilated cardiomyopathy or other myocardial diseases. Such defects could be caused by impaired small vessel blood flow, abnormalities in cell membrane transport or relative differences in left ventricular wall thickness. In 9 patients defects were probably due to attenuation artifacts. Defects in patients with heart diseases were significantly larger than in those without obvious disease. The information content in coronary angiography and 201Tl SPECT overlap but are not congruent. Coronary angiography describes morphology of large coronary vessels, whereas 201Tl SPECT contains information of large and small vessel perfusion as well as membrane transport of 201Tl ions. PMID- 2261293 TI - Deep vein thrombosis of lower extremities. Diagnosis by real time ultrasonography. AB - In 150 patients with possible deep venous thrombosis in the lower extremities, the diagnostic accuracy of real time ultrasonography (US) with 3.5, 5.0 or 7.5 MHz transducers was assessed using venography as standard. In the area of the common femoral/popliteal vein, US was correct in 147 patients, giving an accuracy of 98 percent. There were no false negative studies, giving a sensitivity of 100 percent (60/60) and three false positive studies, giving a specificity of 97 percent (87/90). The results were almost the same using all the three frequencies. The simplicity and accuracy of US make it a useful diagnostic tool. PMID- 2261295 TI - Morphologic changes in the body of the pancreas secondary to a mass in the pancreatic head. Analysis by CT. AB - CT scans of 279 normal subjects and 78 patients with a pancreatic head mass were reviewed. The mean width of the pancreatic body in normal subjects was 15.8 +/- 2.9 mm, but the width decreased with age. The pancreatic head to body width ratio (H/B ratio) was constant (1.45 +/- 0.03). In 56 patients with carcinoma, the pancreatic body width decreased as tumor size increased and uniform atrophy with continuous beading duct was common in large carcinomas. The H/B ratio in small carcinomas (less than 2 cm), however, was significantly smaller than normal (p less than 0.05) and an enlarged pancreatic body was seen in 55 percent of these cases. The pancreatic body width in focal inflammatory masses was large compared to that in carcinomas of comparable size; the H/B ratio (1.57) was close to normal and the duct caliber to gland width ratio was low (0.16), even with large lesions. Non-uniform pancreatic body with discontinuous duct was most commonly associated with pseudocyst. Characterization of the CT appearance of secondary changes in the pancreatic body may help to improve the diagnosis of pancreatic head mass. PMID- 2261294 TI - Ultrasonography and computed tomography in diffuse liver disease with cholestasis. AB - Ultrasonography (US) and computed tomography (CT) were performed on respectively 67 and 42 (altogether 72) patients, for the assessment of intrahepatic cholestasis. The diagnostic ability to differentiate between malignant (17 patients) and benign (55 patients) liver disease was analyzed. Coarse echogenicity of the liver led to inconclusive results in differentiating between cirrhosis (2 out of 29 patients) and malignant infiltration (4 out of 15 patients) by US. Other benign liver diseases in 23 patients, including acute hepatitis, chronic active hepatitis, fatty liver, and liver congestion, were correctly interpreted as benign. CT correctly disclosed malignant liver disease in all cases. A false positive diagnosis of malignancy was encountered in 4 (out of 17) patients with decompensated hepatic cirrhosis because of non-homogeneous expansive areas on CT in 3 cases. The true cause was in 2 patients non-uniform fatty infiltration, and in one patient with acute hepatitis A, small hypodense lesions. Among cholestatic patients, decompensated cirrhosis and malignant liver infiltration could not always be differentiated on US or CT. PMID- 2261296 TI - The cleansing enema. How many for a good quality double-contrast enema? AB - The effects of the 'tap-water enemas till clear' method of bowel cleansing on the technical quality of double-contrast enema (DCE) were studied in 123 outpatients referred for DCE. Patients with one or two tap-water enemas (1.75 litres) before the DCE had significantly more faecal residue and flocculation of contrast medium than patients with three or more enemas. However, the number of enemas did not correlate significantly with mucosal coating. The results suggest that at least three tap-water enemas should be given before DCE. PMID- 2261297 TI - Variations in gastrointestinal melanoma metastases. AB - In 10 patients with gastrointestinal metastases from cutaneous malignant melanoma, metastases to the stomach were found in 2, the small bowel in 9, and the large bowel in 3. Gastric metastases typically appeared as target lesions. However, the morphology of secondary melanoma deposits to the small and large intestine varied significantly, target lesions being only one possible manifestation. Less common appearances of gut metastases were found in 4 patients. One presented atypically with matted loops of distal ileum resulting in prolonged stasis of barium in the affected areas. In 3 patients, infiltrative and stenotic lesions were found in the distal ileum, terminal ileum and cecum. One stenotic lesion of the distal ileum was accompanied by multiple small polypoid lesions more proximally, and the cecal lesion was ulcerated. Six of the patients presented with polypoid and, occasionally, ulcerated and multiple secondary melanoma deposits. Possible causes for variations in morphology are discussed. PMID- 2261298 TI - CT diagnosis of gall stone ileus. AB - We report a case of gall stone ileus in which only small bowel obstruction was seen on the conventional abdominal film and the diagnosis was made by computed tomography (CT). With the availability of CT and its increasing use in the investigation of the acute abdomen, CT examination will occasionally be performed on gall stone ileus patients. Awareness of the CT findings in gall stone ileus will result in early diagnosis leading to a reduction in the mortality rate. PMID- 2261299 TI - Magnetic resonance imaging of the transplanted kidney. Correlation to function and histopathology. AB - Interstitial fibrosis is a frequent finding in biopsies from long-term renal allografts, and may be due to chronic cyclosporine nephrotoxicity or chronic rejection. In this study, long-term renal transplants were investigated with magnetic resonance (MR) imaging, and the results were correlated to histopathology and graft function. Seventeen patients were investigated with MR one to 10 years after transplantation and with simultaneous ultrasonographically guided cortical needle biopsy and function tests. Histopathology included semiquantitative grading of degree of fibrosis and quantitation of ratios of tubular structures to interstitial tissue. The correlation between the histopathological assessment of interstitial fibrosis and graft function was good. Poor differentiation between the renal cortex and the renal medulla at MR imaging was correlated to high degree of interstitial fibrosis in the kidney transplants as well as to reduced graft function. MR examination may thus be of value in the evaluation of long-term renal transplants with chronic functional changes. PMID- 2261300 TI - Renal osteodystrophy. Radiological diagnosis compared with a new radioimmunoassay method of parathyroid hormone. AB - The parathyroid hormone concentration in the blood measured by the 'two-site radioimmunoassay', which is specific for the biologically active parathyroid molecule (parathyrine), was compared with the radiological manifestations of secondary hyperparathyroidism (HPT) on magnification radiographs of the phalanges in patients undergoing maintenance hemodialysis and in patients with renal allografts. Sensitivity of radiology for the diagnosis of HPT proved to be high (88%), whereas specificity was low (30%). Statistical analysis showed that there was a good correlation between the parathyrine levels and the intensity of radiological changes in the phalanges in patients with renal allografts (coefficient of Krueger-Spearman = 0.65). In patients undergoing hemodialysis the correlation between laboratory parameters and radiological changes was poor. PMID- 2261301 TI - Contrast media and pain in patients with acute ureteral stone obstruction. A comparative study with iohexol and metrizoate. AB - A randomized study was conducted in 43 patients who were in pain due to acute ureteral obstruction. Emergency urography was performed in all patients, using either a low osmolar non-ionic (iohexol) or a high osmolar ionic (metrizoate) contrast medium. Increase of pain following injection of contrast media was found in 56 percent of all patients. Increase of pain occurred with both contrast media without any difference between the degree of pain nor the number of patients who experienced an increase of pain. Delayed excretion was considered the only reliable indicator of the degree of obstruction in the present study. Nineteen (68%) of the 28 patients with a delayed excretion greater than 10 min experienced increased pain while the incidence of pain increase was significantly lower (33%) in patients without that sign of ureteral obstruction (p less than 0.05). The increase of pain was not associated with a simultaneous increase of the mean arterial blood pressure. PMID- 2261302 TI - Systemic, pulmonary and renal haemodynamic and renal morphologic effects of intravenously infused iodixanol. A study in the pig of a new iso-osmolar contrast medium. AB - The systemic, pulmonary and renal haemodynamic effects following an intravenous infusion (1 ml/s, 4 ml/kg) of a non-ionic isoosmolar contrast medium (iodixanol) were investigated in 8 pigs. Histopathologic changes occurring after infusion of iodixanol were studied by repeated renal biopsies. Iodixanol caused a significant increase of cardiac output, mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary arterial occlusion pressure and mean arterial pressure. There was a decrease of the systemic and pulmonary vascular resistances. Most renal biopsies showed no pathologic findings after infusion of iodixanol but in 3 specimens proteinaceous content was observed 15 min after infusion. PMID- 2261303 TI - Oxygen saturation of the low osmolar contrast media iohexol, ioxaglate and iodixanol. Effects on contractile force and frequency of ventricular fibrillation in the isolated rabbit heart. AB - During coronary angiography the exchange of blood with a contrast medium solution causes a period of hypoxia. To investigate whether oxygen saturation of the contrast medium could be beneficial, low osmolar contrast media were infused without and with oxygen saturation into the coronary arteries of the isolated rabbit heart. Iohexol (150-300 mg I/ml, without NaCl or with 20-30 mM NaCl), iodixanol (320 mg I/ml, contains 24 mM NaCl) and ioxaglate (160 mg I/ml, contains 75 mM Na+) were infused without and with oxygen saturation. The decrease in contractile force (CF) of the heart, from the contrast medium solutions, was reduced when the solutions were saturated with oxygen. Oxygen saturation of iohexol (350 mg I/ml, without or with 10 mM NaCl) did not change the frequency of ventricular fibrillations (VF). Low osmolar contrast media, when saturated with oxygen, thus caused a reduced decrease in CF without changing the frequency of VF. This might be beneficial in clinical cardioangiography by reducing the adverse effects from the media. PMID- 2261304 TI - Sodium addition and/or oxygen saturation of iohexol during normal and reduced perfusion pressure. Effects on contractile force and risk of ventricular fibrillation in the isolated rabbit heart. AB - The influence on contractile force (CF) and the propensity for ventricular fibrillation (VF) from infusing the non-ionic contrast medium iohexol during normal (75 cm H2O) and reduced perfusion pressure (35 cm H2O) were investigated in the isolated rabbit heart. Both during normal and reduced perfusion pressure iohexol (150 mg I/ml) with oxygen saturation caused a smaller reduction of CF than iohexol without oxygen. During reduced pressure iohexol with sodium addition (28 mM NaCl) caused less depression of CF than iohexol without sodium. The combination of sodium addition and oxygen saturation had the least influence on CF. Iohexol (350 mg I/ml) without sodium had a similar fibrillatory propensity during both normal and reduced pressure. Enriching iohexol with 28 mM NaCl decreased the risk of VF. The decrease was similar during both normal and reduced pressure. The risk of VF from oxygen saturation of iohexol (350 mg I/ml, without sodium) was similar during both normal and reduced pressure. It is concluded that a small addition of sodium and/or oxygen saturation of a non-ionic monomeric contrast medium have beneficial effects on the heart both during normal perfusion pressure and during ischemia. PMID- 2261305 TI - Granulocyte chemotaxis. Influence of radiographic contrast media on the chemoattractive properties of serum. AB - One of the important functions of granulocytes is the ability to respond to a chemoattractive signal by migration. The influence of radiographic contrast media (CM) on the chemoattractive properties of serum was investigated by under agarose technique for chemotaxis. No chemotactic response was seen when serum was incubated with different concentrations of CM after heat inactivation. The CM did not generate the heat stable complement split product C5a-desarg which would have resulted in a chemotactic response. Without heat inactivation all complement available in the serum was activated by the agarose in the chemotaxis assay. Low concentrations of iohexol and iodixanol brought about an increased chemotactic response relative to a reference with saline instead of CM. This may be due to activation of heat labile chemoattractants from other sources than the complement cascade. At high concentrations of all five investigated CM, a decreased number of granulocytes migrated over a shorter distance when compared with the reference, and this may be due to interactions between the CM and chemoattractants or their precursors. PMID- 2261306 TI - Iopromide versus diatrizoate. A comparative study of adverse reactions. AB - One hundred patients were at random given an intravenous injection of equal amounts of either diatrizoate or iopromide. Subjective patient discomfort and objective parameters of adverse reactions were recorded. There were significantly fewer patients with adverse effects in the iopromide group, both as an overall estimate and especially for heat sensation, nausea and increase in heart rate. Iopromide is recommended for increased patient safety. PMID- 2261307 TI - Niobium filters for dose reduction in pediatric radiology. AB - The performance of a niobium filter, with K-edge at 19 keV, and a copper filter have been studied concerning absorbed dose, image quality and tube loading. Absorbed doses were measured with TLD. To evaluate image quality a perspex phantom with image quality test objects was used. In comparison with a conventional filter made of copper no significant advantage was obtained with the niobium filter. PMID- 2261308 TI - Supercoiling of f-actin filaments. AB - In the X-ray diffraction pattern from oriented gels of actin-containing filaments sampling of layer lines indicating the development of a well-ordered pseudo hexagonal lattice within the gels at interfilament spacings as large as 13 nm is observed. This value exceeds by 3 nm the largest estimate of an external diameter of pure f-actin. The development of layer line sampling is always accompanied by: (i) the appearance of strong forbidden meridional reflections on the 5.9- and 5.1 nm layer lines; (ii) a drastic intensification of the first (expected) 2.75-nm meridional reflection by a factor of about 4; (iii) the appearance of streaks, connecting near-meridional reflections on the 5.9-, 5.1-, and 37-nm layer lines; and (iv) a slight decrease in the number of subunits per turn of the basic f actin helix. All these features strongly indicate that f-actin filaments are supercoiled and make regular local contacts between themselves, which may lead to periodic distortions of the mobile external domain in the actin subunits. PMID- 2261309 TI - Melting of myosin and tropomyosin: electron microscopic observations. AB - A method was devised to maintain a very low angle (2-3 degrees) during the metal casting of specimens for electron microscopy. With this modified rotary shadowing procedure the melting of myosin and tropomyosin (TM) was investigated. When protein solutions were sprayed on mica sheets and then heated to melt alpha helices, myosin molecules did not show any sign of chain separation but appeared to have collapsed into loose clumps. A few molecules showed separation of the two chains at the light meromyosin-heavy meromyosin hinge region. Heating myosin in bulk solution at 65 degrees C before spraying caused extensive fusing of the myosin heads. In contrast, in the case of TM, separation of the chains appeared to occur at temperatures at which the unfolding of alpha-helices had been shown by circular dichroism. Dissolution of TM and myosin in 0.5% SDS followed by 150 fold dilution led to single chain species. This method capable of detecting single chain peptides of melting TM whose thickness is of the order of 1 nm may be applicable to the study of the structure of proteins previously not considered possible. PMID- 2261310 TI - Morphologic effects of sulfur-substituted fatty acids on rat hepatocytes with special reference to proliferation of peroxisomes and mitochondria. AB - The morphologic effects of different sulfur-substituted mono- and dicarboxylic fatty acids on rat hepatocytes have been examined. The substance 1,10 biscarboxymethylthiodecane (BCMTD) is blocked for both beta- and omega-oxidation, whereas 1-monocarboxymethylthiodecane (CMTTD) is only non-beta-oxidizable. At equimolar doses BCMTD was considerably more potent than CMTTD in hypertrophic liver enlargement. At the ultrastructural level, BCMTD increased the volume fraction of the peroxisomes by a factor of 8, and their size and number by factors of 2.1 and 6.4, respectively. Furthermore, the frequency of dense cores in the peroxisomes decreased from 60 to 8%. CMTTD resulted in an increased volume fraction of peroxisomes (4.5-fold), in the mean volume (1.9-fold), and in the number of peroxisomes (3.7-fold). At the mitochondrial level, a gradual development toward megamitochondria was observed after CMTTD administration. BCMTD, however, increased the number of mitochondria but they tended to be smaller. Administration of both acids increased peroxisomal beta-oxidation and mitochondrial carnitine palmitoyltransferase activity, whereas the lipid content of hepatocytes was reduced with increasing doses of CMTTD and especially BCMTD. The acid 1-mono(carboxyethylthio)tetradecane (CETTD), which is able to undergo one cycle of beta-oxidation, caused no change in liver weight, and only marginal effects on peroxisomes and mitochondria were observed. In contrast to the BCMTD and CMTTD feeding, the animals developed a tremendous accumulation of fat in the livers: the volume fraction of lipid droplets increased 23-fold after CETTD feeding. PMID- 2261311 TI - The atrial myocardial cells of mouse heart: a structural and stereological study. AB - Structural and stereological studies of mouse atrial myocardial cells, carried out in the same fashion as our previous investigations on mouse ventricle, demonstrate an extremely well-developed sarcoplasmic reticulum (SR) in atrial cells. The volume fraction (Vv) of the SR exceeds 12% in mouse atrial cells; perimyofibrillar network SR constitutes the major portion. We have confirmed the findings of Bossen et al. (1981, Tissue Cell 13, 71-77) of a difference between atria in terms of coupling density, the right atrium having a significantly lower incidence of interior junctional SR than the left. The SR of mouse atrium comprises a rich variety of specialized segments, including the IJSR, peripheral junctional SR, corbular SR, cisternal SR (including regions similar to fenestrated collars of striated skeletal muscle SR), as well as a peculiar form of extended junctional SR (EJSR). Although less frequent in occurrence than corbular SR, the EJSR seems closely related, since it occurs in multiple clusters at or near the Z-line regions, contains internal granular densities, and bears surface-connected structures resembling junctional processes. Seen in thin sections, mouse atrial EJSR elements are more complex than corbular SR, being larger in diameter and frequently circular in profile. Thick-section and serial section analyses reveal that bodies of EJSR are in fact hollow spheroids. The transverse-axial tubular system of mouse atrium is rather poorly developed in comparison to its ventricular counterpart. The Golgi apparatus and associated specific atrial granules are prominent cell components. "Focal ellipsoidal deposits" (FEDs) previously described by Page and co-workers (1986, Amer. J. Physiol.) are consistently located adjacent to the Golgi region, but immunocytochemical staining for two different segments of atrial natriuretic peptide reveals no specific reaction in FEDs, whereas the SAGs are densely labeled for both antibodies. PMID- 2261312 TI - Analysis by in situ hybridization and autoradiography of sites of replication and storage of single- and double-stranded adenovirus type 5 DNA in lytically infected HeLa cells. AB - The distribution in the different compartments of infected nuclei of double stranded (ds) and single-stranded (ss) adenovirus type 5 (Ad5) DNA and of the sites of viral DNA replication were examined on thin sections of Low-icryl embedded material. The DNA is visualized with a biotinylated viral probe and immunogold labeling of biotin, and its replication is monitored by high resolution autoradiography after short pulses with tritiated thymidine. The first detectable sites of viral DNA, named early replicative sites, contained all the ss and ds viral DNA and viral replicative activity. At a later stage of nuclear transformation, they gave rise to two new structures. The compact fibrillar ssDNA accumulation sites enlarged greatly and became transformed functionally to become a transient site of accumulation of large numbers of ss replicative intermediates. Double-stranded viral DNA and its replicative activity shifted primarily into immediately surrounding fibrillogranular peripheral replicative zones. Ad5 DNA replication continues in the ssDNA accumulation sites but it is intermittent, whereas in the peripheral replicative zones it is continuous. Still later in infection, a single, large, centrally located mass of dense fibrils, the viral genome storage site, developed in each nucleus which proved to be the main site of storage of nonreplicating, nonencapsidated, ds viral genomes. We discuss the possible distribution of the various viral DNA replicative intermediates among these virus-induced intranuclear structures. PMID- 2261313 TI - The need for continuous training in food factories. AB - The dissemination in food factories of the organisms I have referred to earlier, represent significant and interesting issues of public health concern. Yet there seem to be difficulties in incorporating material in education-training information programmes explaining merely the most simple and basic facts about the risk involved in food being contaminated in food factories. Such educational programmes are essential components in the overall scheme of foodborne disease control, yet they often represent the weakest links in the control chain. There has been a decline in the emphasis on food hygiene in some programmes at the level of institutions of higher education, and a de-emphasis on food hygiene has occurred over the past few decades in schools of veterinary medicine in some parts of the world. This committee has taken active steps to improve this situation by convening a professorial consultation on post-graduate teaching in advanced food microbiology, Copenhagen 1989 (Park, 1990). The public, as well as politicians, focus for the time being on chemical contamination of foods, possible presence of residues, thereby ignoring the fact that statistically it is not the residues that cause deaths which count, but, without a shadow of doubt, the foodborne pathogens. This fact emphasizes the need for intensive training in preventive hygienic measures. Since representatives of the food industry are participating in the Symposium, I would like to balance the problems by saying: we all share a responsibility in securing education in food hygiene in food factories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261314 TI - Immunofluorescence microscopic studies on distribution of Lactobacillus kefiranofaciens and Lactobacillus kefir in kefir grains. AB - Immunofluorescence staining was applied to observe distribution of two Lactobacillus species in kefir grains with cauliflower floret forms. Kefiran producing, encapsulated Lactobacillus kefiranofaciens was located all over the grain and increased toward the center, while Lactobacillus kefir populated only a small region at the surface layers. PMID- 2261315 TI - Estimation of most probable number of Salmonella in retail samples of minced pork. AB - The number of salmonellae in 174 samples of minced pork was determined by the Most Probable Number (MPN) method in two separate laboratories. The material examined was taken from a collection of samples which were Salmonella positive in an earlier study. The MPN estimation was carried out using portions of original samples which had been divided (2 x 100 g) before the initial examination and which had been deep frozen and stored for 1 to 14 weeks at -18 degrees C until re examination. Of the 174 samples initially positive for Salmonella, 131 (75.3%) were positive on re-examination using pre-enrichment in buffered peptone water (BPW) and selective enrichment in Rappaport-Vassiliadis medium (RV) and in tetrathionate medium according to Muller-Kauffmann (MK). The majority of the samples gave Salmonella counts below 1000/100 g (96.7% at lab. A and 97.3% at lab. B). Comparison of the results from both laboratories showed good agreement in the distribution pattern of the frequencies within the MPN classes, but agreement between the same sample pair was poor (r = 0.23). RV medium proved to be superior to the MK medium. PMID- 2261316 TI - Influence of freezing-thawing and refrigeration on R-plasmid (pRPJ24) stability in Enterobacter cloacae 94R. AB - The effect of twenty freezing (-20 degrees C) and thawing cycles of Enterobacter cloacae 94R cells containing the R-plasmid pRPJ24 inoculated into broth and ground beef meat samples revealed no loss of resistance due to plasmid instability. In addition, low temperature storage at 4 degrees C did not produce any significant loss of the tetracycline and kanamycin resistances encoded on the pRPJ24 plasmid. The results of this study indicated that indigenous R-plasmids like pRPJ24 are stable in resident recipients like E. cloacae 94R in ground beef. However, the proportion of viable cells containing the pRPJ24 plasmid decreased significantly after 20 freezing-thawing cycles over 14 days incubation at 4 degrees C. PMID- 2261317 TI - Optimal determination of most probable numbers. AB - Choosing the design of a dilution series experiment on the basis of availability of most probable number tables can result in a non-optimal design. Similarly, certain tables and/or rules for declaring dilution series results 'improbable' do not always give optimal decisions. Further, tables of most probable number confidence intervals are not all based on the same assumptions and give different intervals--which should be used? The aim of this article is to draw microbiologists' attention to these issues and to suggest practical solutions. PMID- 2261318 TI - Biological control of Penicillium digitatum by Trichoderma viride on postharvest citrus fruits. AB - In previous studies it was shown that Trichoderma viride, isolated from Spanish citrus packing houses, showed antagonistic activity against Penicillium digitatum in in vitro laboratory tests. In the present in vivo studies Navelina oranges, protected with aqueous suspension of T. viride (2.5 x 10(6) to 2.5 x 10(9) spores per ml), showed an increase in resistance toward P. digitatum. Oranges, inoculated with P. digitatum, did not produce lesions after 5 days when T. viride was applied 48 h or 72 h before inoculation. PMID- 2261319 TI - Antibiotic prophylaxis of late bacteremic vascular graft infection in a dog model. AB - This study was undertaken to determine the efficacy of a single-dose antibiotic injection to prevent late bacteremic vascular graft infection. Twelve dogs had thoracoabdominal aortic bypass with expanded polytetrafluoroethylene grafts. One month later, a bacteremic challenge was produced by rapid intravenous injection of 5 x 10(8) Staphylococcus aureus. Dogs were treated by pairs, each dog of a pair being randomly assigned to receive either 0.5 g ceftriaxone (group I, n = 6) or saline (group II, n = 6), intramuscularly, 90 minutes before challenge. Grafts were harvested seven days after bacteremic challenge. They were cut into 10 fragments, each of which were submitted to bacterial counts. Results of bacterial counts were expressed as colony forming units per square centimeter of graft segment. The overall infection rates were zero of six grafts in group I and four of six in group II (p less than 0.05). In group I, none of the 60 graft fragments were found to be culture positive (p greater than 0.01). Bacterial counts from the 24 infected fragments were highly variable, ranging from 12 colony forming units/cm2 to 64 x 10(3) colony forming units/cm2. Serial quantitative blood cultures revealed a similar decrease of bacteremia in both groups with 2.4 +/- 0.9 x 10(2) (group I) and 1.2 +/- 0.9 x 10(2) (group II) colony forming units/ml at three hours. Mean ceftriaxone serum level was 26 +/- 18 mg/L at the time of bacteremic challenge. These data suggest that a single dose of ceftriaxone given before bacteremic challenge is sufficient to prevent late bacteremic vascular graft infection in this model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261320 TI - Arterioportal fistulas: twelve cases. AB - During the last 20 years, we encountered 14 arterioportal fistulas in 12 patients. Gastrointestinal hemorrhage or mesenteric artery insufficiency were the most frequent conditions found after the diagnosis. Arterioportal arterial fistulas were congenital in two cases and acquired in 10; seven of these 10 were iatrogenic. One patient had three successive and different sites of arterioportal fistula. The fistula originated from a branch of the celiac axis in nine cases, the superior mesenteric artery in three, and the inferior mesenteric artery in two. One patient died of massive anal bleeding before any treatment was possible. Eight fistulas were treated surgically and five by arterial embolization. After treatment there was no early mortality, while hemorrhagic and ischemic complications regressed in all cases. Three hemorrhagic recurrences were observed in patients with preexisting cirrhosis (two cases) or by recurrence of a congenital arteriovenous fistula (one case). Closure of symptomatic arterioportal fistula is justified. The choice of the most appropriate method for each patient should be discussed between the surgeon and interventional radiologist on a case by case basis. PMID- 2261321 TI - Pancreaticoduodenal artery aneurysms associated with celiac axis stenosis: report of two cases and review of the literature. AB - We have endeavored to define the incidence of pancreaticoduodenal artery aneurysm associated with stenosis of the celiac axis and to address modalities in this setting. This association was found in 23 of 34 cases. Aneurysmal dilation of the pancreatic arteries associated with celiac axis stenosis is not accidental and seems to be due to increased flow through the peripancreatic arteries. Hemorrhagic complications, i.e., peripancreatic hematoma, hemoperitoneum, ductal hemorrhage, were the initial manifestation in 16 of 34 cases. Isolated aneurysms were treated by resection, exclusion or embolization without any complications. For associated aneurysms, resection and exclusion were employed. Pancreatoduodenectomy was required in three cases in which bleeding was uncontrollable. In six cases, the celiac axis was restored either by arterial reconstruction, aortohepatic bypass, or division of the arcuate ligament. Four patients died. All had been operated on for ruptured aneurysm. None of the deaths was directly due to ischemic compromise of the celiac artery bed. Because of the risk of rupture, all pancreaticoduodenal artery aneurysms should be treated surgically after appropriate investigation to detect associated celiac axis stenosis. Revascularization of the celiac axis is indicated whenever blood flow is reduced or, routinely, to reduce high peripancreatic collateral flow, particularly when collaterality is due to arcuate ligament-related stenosis. PMID- 2261322 TI - Neurologic complications of axillary and brachial catheter arteriography in atherosclerotic patients: predictive factors. AB - Catheter arteriography by the axillary or brachial route can be responsible for central neurologic complications. The objectives of this prospective study were to define the predictive factors of these complications and determine their incidence. This report is based on 288 consecutive arteriography sessions performed between January 1985 and June 1987. All patients had arterial atheromatous pathology. Ten central neurologic complications (3.5%) occurred, two of which (0.7%) were permanent. Four factors were significantly associated with increased incidence of central neurologic complications: antecedent transient ischemic attack (p less than 0.001); tight (greater than 80%) stenosis of at least one internal carotid artery (p less than 0.02); angina pectoris (p less than 0.05); age over 80 years old (p less than 0.001). Seldinger's or Dos Santos' techniques are preferable to axillary or brachial catheter techniques for investigation of the lower limbs and the abdominal aorta. The former obviates the need to catheterize the aortic arch and reduces the risk of embolism to the supraaortic arteries. Digital venous arteriography is an alternative to aortic arch catheterization when investigating the supraaortic arteries in the presence of risk factors. PMID- 2261323 TI - Nosocomial infection surveillance in a vascular surgery unit. AB - An epidemiological nosocomial infection surveillance program was conducted in the Vascular Surgery Unit of Purpan University Hospital, Toulouse, France, involving 389 patients hospitalized between June 1 and November 30, 1988. The methodology and inclusion criteria used were those of the Centers for Disease Control of Atlanta. Twenty-six patients had 30 nosocomial infections according to these criteria, a prevalence of 6.7% and an incidence of 5.6%. These patients were hospitalized for 485 of a total of 4317 days; bed occupation due to infection was 11.23%. Of the 30 infections, the most common were 13 (43.5%) urinary tract infections and six (20%) operative wound infections. E. coli (8 isolates) and Staphylococcus aureus (7 isolates) were the most frequently encountered offending microorganisms. A case-control study showed that mean hospitalization time was increased by 11 days (p less than 0.001) in infected patients and that antibiotics were used four times as often in these patients (p less than 0.001). Urinary tract infection represented 50% of nosocomial infections in our study. The prevalence and incidence of wound infection was 20% and 8%, respectively. Nosocomial infection always occurred in patients already infected or who were debilitated. Nosocomial infections prolonged hospitalization by 57%. PMID- 2261324 TI - Free-floating thrombus of the extracranial internal carotid artery. AB - Free-floating clots of the extracranial internal carotid artery are generally considered as surgical emergencies. This retrospective study analyzes six free floating clots diagnosed by arteriography. Three of these patients had a fixed stroke while the other three had an evolving stroke. Three patients had antecedent ocular or hemispheric transient ischemic attacks. The causes of free floating clots in the internal carotid artery were atheromatous stenosis in two cases, ulcerated plaque in three cases, and carotid artery dissection in one. All six patients were seen late, approximately 15 hours after their neurologic accident. They were treated with intravenous heparin over a two to five week period. Repeat arteriograms demonstrated complete clot lysis in four instances, while partial lysis was seen in one case. Moderate extension of thrombus occurred in one case only. No further neurologic complications were noted during the treatment by heparin. As indicated by follow-up arteriographic findings, secondary surgery was performed for major carotid lesions and residual clots in five cases. The free-floating thrombus syndrome of the carotid artery should not be considered as a surgical emergency when discovered late in the wake of an acute neurologic accident. PMID- 2261325 TI - Renal failure after operation for abdominal aortic aneurysm. AB - Among 656 patients undergoing surgery for abdominal aortic aneurysm, 81 patients (12%) developed postoperative renal failure. Before operation hypotension and shock occurred in 88% of the patients with ruptured aneurysm, whereas none of the patients operated electively were hypotensive. Dialysis was performed in 32 patients, while the remaining 49 patients were managed without dialysis. Within 30 days after the operation 47 patients (58%) had died. There was no difference in mortality between patients in dialysis and patients managed without dialysis. Thirteen patients died during follow-up. In six cases the death was caused by renal failure only or in combination with failure of other organs. Analysis of the cumulative survival shows that, if the patients survive the postoperative period, their life expectancy is comparable to that of patients without renal complications. PMID- 2261326 TI - End-to-side aortoprosthetic anastomoses: long-term computed tomography assessment. AB - Fifty-two asymptomatic patients underwent routine computed tomographic evaluation of aortobifemoral bypass grafts implanted end-to-side on the aorta five to 10 years after operation. Anteroposterior diameters were measured at the level of the stem and the limbs of the graft, the aortoprosthetic anastomosis, and the infraanastomotic aorta. The stems of the prostheses were found to be dilated between 30 and 110% (mean 58%) of initial values. The limbs of the graft were dilated between 15 and 150% of initial values, the mean being 52%. The anteroposterior diameter of the aortoprosthetic anastomosis measured between 27 and 48 mm with a mean of 32 mm. Eight patients (15%) had an anastomotic false aneurysm. The aorta distal to the prosthetic anastomosis was completely occluded in 48 cases (92%). A mural thrombus was encountered at the level of the aortoprosthetic anastomosis in 21 (40%) patients. These findings raise questions as to the possible role of side-to-end aortoprosthetic anastomoses in the genesis of anastomotic dilatations, false aneurysms, intraprosthetic thrombosis, and thrombosis of the branches of aortofemoral bifurcation prosthetic grafts. PMID- 2261327 TI - Antibiotic therapy for arterial infection: lessons from the successful treatment of a mycotic femoral artery aneurysm without surgical reconstruction. AB - A mycotic femoral artery aneurysm developed in a diabetic man with bacteremia from a Staphylococcus aureus urinary tract infection. Because of severe concomitant congestive heart failure and hypothyroidism, surgical reconstruction of the femoral artery was deferred while the patient received an intensive course of intravenous nafcillin. This led to stabilization of the size of the femoral aneurysm for two years, during which time it remained asymptomatic. Three such cases of nonsurgical treatment of a mycotic aneurysm have been documented. Surgical ligation, drainage, and bypass remain the mainstay therapies for mycotic aneurysms, but these cases demonstrate the possibility of sterilizing a primary arterial infection under the highly selected circumstances of an exquisitely sensitive organism, absence of periarterial abscess and readily observable anatomic location. Most importantly, these cases provide assurance that a six week course of parenteral antibiotics is a reasonable adjunctive treatment for residual endovascular infection. PMID- 2261328 TI - St. Anthony's fire: successful reversal of ergotamine-induced peripheral vasospasm by hydrostatic dilatation. AB - A 60-year-old trauma victim developed severe ischemia of all four extremities following administration of heparin-dihydroergotamine as prophylaxis against deep venous thrombosis. Despite cessation of heparin-dihydroergotamine and infusion of intraarterial papaverine into the right femoral artery, both lower extremities progressed to frank gangrene and amputation (above-knee on the left and below knee on the right). However, both ischemic upper extremities were salvaged following intraoperative hydrostatic dilatation with balloon catheters. Ergotism is an avoidable and potentially treatable cause of peripheral gangrene in the critically-ill patient. PMID- 2261329 TI - Spontaneous aneurysm of the extracranial vertebral artery associated with spinal osseous anomaly. AB - Spontaneous aneurysms of the extracranial vertebral artery are uncommon. We report the case of an aneurysm located at the second cervical vertebra, associated with a congenital spinal malformation. Computed tomographic scan and arteriography were diagnostic. After proximal ligation of the vertebral artery, the aneurysm was incised and the distal vertebral artery was revascularized by an infraoccipital carotid-to-vertebral artery vein bypass. PMID- 2261331 TI - The risk of transmission of AIDS and other blood-related diseases during routine malaria activities. PMID- 2261330 TI - Basic data related to lipid abnormalities in peripheral vascular disease. PMID- 2261332 TI - Acquired immunodeficiency syndrome (AIDS). Prescribing of HIV tests by sentinel general practitioners. PMID- 2261333 TI - Diarrhoeal Diseases Control Programme. Household surveys. PMID- 2261334 TI - Arboviral surveillance. Update: St. Louis encephalitis in Florida and Texas, 1990. PMID- 2261335 TI - Oncology Nursing Society: focus on education. PMID- 2261336 TI - The surgical oncologist as a resource. PMID- 2261337 TI - Evaluation of a cancer prevention and detection continuing education program for nurses. AB - To stay relevant and continue to meet the needs it was created to meet, a 15-year old continuing education program in cancer prevention and detection for nurses has found change a constant. The process it has followed in evaluation- identifying goals, gathering and analyzing data, and reporting the results--can be compared with the nursing process in which feedback prompts changes and initiates the evaluation process all over again. The most recent part of the program's ongoing evaluation involved 70 nurses enrolled in a three-week continuing education program in which the nurses were pretested and posttested to measure cognitive gain in nine content areas covered in classroom and clinical instruction. Paired t test scores showed overall that students' scores improved significantly, increasing a mean of 18% across all categories. These results indicate that students are gaining knowledge, and measures of skills, improving on those already in place, are being added in what is only the latest modification of a program shaped by feedback from students, faculty, and research. PMID- 2261338 TI - University-based postresidency training programs in surgical oncology. AB - The issue of postresidency training in surgical oncology engenders much debate, particularly as it impacts on general surgery training. With the goal of enhancing instruction in surgical oncology in the future, a survey was conducted to assess the role of surgical oncology programs and educational activities within university-based surgery training programs. The results of the study demonstrate an increased emphasis on surgical oncology training over the past five years. The findings also indicate that education activity in surgical oncology in all departments of surgery has increased greatly, as demonstrated by an increased number of specific teaching rounds and conferences. The impact of this increased awareness on the future of surgical oncology training is discussed. PMID- 2261339 TI - Medical oncology in a sophomore medical student pathophysiology course. AB - At the University of Colorado School of Medicine, a Medical Oncology unit was first included in the Sophomore Medical Student Pathophysiology Course (MED 6000) in the academic year 1985-1986. Cancer education is important in the preclinical curriculum, because medical students and physicians in most specialties will encounter a significant number of patients with cancer, the second leading cause of death in the United States. Described here is the development of the Medical Oncology unit in MED 6000, how both the mechanics and objectives of the course have changed, and how these changes have affected the student evaluation of the course. PMID- 2261340 TI - Attitudes and practices regarding adjuvant chemotherapy in node-negative breast cancer. AB - Eight months after an NCI "Clinical Alert" was issued a survey was conducted to examine attitudes and practices regarding the use of adjuvant chemotherapy for node-negative breast cancer among Connecticut physicians most experienced in the care of such patients. Respondents (N = 66) indicated that the communication prompted change in case management practices; 65% reported increased use of adjuvant chemotherapy in treatment of women with node-negative disease. Seventy seven percent of physicians who responded now consider adjuvant chemotherapy for node-negative patients to be the standard of care in their community. Opinions regarding the NCI strategy were more equivocal, with 44% of respondents terming the issuance of the Clinical Alert "inappropriate." Our findings suggest that real change in the treatment of breast cancer may have been precipitated by the NCI's action. PMID- 2261341 TI - Cancer patients' concerns: congruence between patients and primary care physicians. AB - To investigate whether physicians perceive concerns of cancer patients in the same way as patients, we asked primary care physicians and cancer patients to complete an instrument that allowed each to indicate their views of the relative importance of a variety of treatment and disease-related concerns. The instrument was completed by 195 physicians (56% response) and 119 newly diagnosed breast, lung, and colorectal cancer patients (50% response). Psychometric analysis of responses to the instrument revealed two components: general concerns and physician-treatment concerns. For both the physician and the patient groups, internal consistency (coefficient alpha) of these two components was high (greater than .83). Within the patient group, scale scores did not differ as a function of performance status, cancer type, extent of disease, or age. For physicians, scale scores were not related to years in practice, board certification, or number of new cancer patients seen per year. A comparison of scale scores between groups indicated that there was good physician-patient congruence on only one of the two concern components. Physicians do not adequately appreciate the extent of concern patients have with regard to treatment and physician interaction issues. PMID- 2261342 TI - Expression of integrins in human bone marrow. AB - Expression of integrins, a superfamily of glycoprotein alpha/beta heterodimers which integrate the cytoskeleton with the extracellular matrix and/or mediate cell-cell adhesive interactions, was examined on normal and leukaemic bone marrow cells by immunohistochemistry and immunotransmission electron microscopy (immuno TEM). Among the beta 1/VLA molecules studied, VLA-2 and 6 were expressed on megakaryocytes and platelets, while VLA-4 was present on 40% of haemopoietic cells, including monocytes, erythroblasts and immature cells; this molecule was typically localized at sites of intercellular contact, as seen by immuno-TEM, suggesting it may be involved in interactions among haemopoietic cells during differentiation. In human long-term bone marrow cultures (LTBMC), VLA-1 and 3 were present respectively on 35% and 40% of the adherent cells which included fibroblasts and endothelial cells, as shown by double-labelling experiments; VLA 2 was expressed only on a subpopulation of fibroblasts. beta 2/LeuCAM molecules were absent from platelets, megakaryocytes and HLA-DR+/myeloperoxidase- early myeloid precursors, and appeared progressively during maturation in both lymphoid and myeloid cells. Expression of beta 3/cytoadhesin molecules was restricted to megakaryocytes and platelets and, in the adherent layer of LTBMC, to endothelial cells. The regulated expression and specific localization of integrins in the bone marrow suggest that these molecules may have a role in normal haemopoiesis. PMID- 2261343 TI - Identification of mRNA for PDGF B-chain in human megakaryocytes isolated using a novel immunomagnetic separation method. AB - A rapid and simple method has been developed for the separation of pure populations of intact human megakaryocytes from whole bone marrow. Megakaryocytes were specifically recognized using monoclonal antibodies coupled to magnetizable articles. Cells labelled with the magnetizable probe were separated from unlabelled cells by introduction of a magnetic field. The technique yields megakaryocyte suspensions with a purity of greater than 98%. Electron microscope examination showed that the ultrastructure of the isolated megakaryocytes was well preserved. Using this method of cell purification, we have investigated expression of the gene for platelet-derived growth factor (PDGF). RNA was isolated from cells harvested from either ribs or posterior iliac crest. The RNA was spotted onto nitrocellulose, and then hybridized using a c-sis riboprobe specific for PDGF B chain mRNA. We demonstrate that mRNA for PDGF B-chain is identifiable in samples of 50,000 cells. We conclude that PDGF is synthesized by the megakaryocyte. PMID- 2261344 TI - Prognostic factors in stage AO B-cell chronic lymphocytic leukaemia. AB - 85 patients presenting to a single centre with stage AO B-cell chronic lymphocytic leukaemia (B-CLL) have been studied. The duration of follow-up has ranged from a minimum of 1 year to a maximum of 18 years with a mean of 6 years. 14 patients have had progressive disease and 23 patients have died, of whom nine had CLL-related deaths. We assessed the prognostic significance of the following parameters: age at presentation, sex, haemoglobin concentration, initial lymphocyte count, surface membrane phenotype, serum immunoglobulin levels at presentation and karyotype. None of these factors were predictive of survival, but there was a correlation between initial lymphocyte count, surface immunoglobulin MD lambda phenotype, and complex karyotypic abnormalities and disease progression. Two patients with a complex karyotype have been followed for more than 5 years without evidence of progression. PMID- 2261345 TI - Correlation of chromosome abnormalities with laboratory features and clinical course in B-cell chronic lymphocytic leukaemia. AB - 141 patients with B-cell chronic lymphocytic leukaemia (B-CLL) have been studied for a minimum of 12 months and a maximum of 25 years. 30 of 133 patients (32.5%) had greater than 10% FMC7 positive peripheral blood lymphocytes and 19 of 131 patients (14.5%) had a serum or urinary paraprotein. At presentation 88 patients were stage A0, 18 A1, 18 A2, 11 B and six C. 44 (31%) had progressive disease and 42 (30%) died during the study period. 63 patients had a normal karyotype, 75 a clonal abnormality and in three no metaphases were obtained. The finding of a complex karyotypic abnormality was significantly associated with lambda surface phenotype (P less than 0.01), the presence of greater than 10% FMC7 positive cells (P less than 0.025), and the presence of a paraprotein (P = 0.025). Patients whose leukaemic cells had a complex karyotype and those with structural abnormalities of chromosomes 14 and 6 required treatment earlier than those with a normal karyotype. PMID- 2261346 TI - 'MACHO' chemotherapy for stage IV B cell lymphoma and B cell acute lymphoblastic leukaemia of childhood. United Kingdom Children's Cancer Study Group (UKCCSG). AB - An intensive 6-month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym 'MACHO', to treat 24 newly and consecutively diagnosed children, 13 with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) and 11 with B-cell acute lymphoblastic leukaemia (B-ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS+) received planned additional megatherapy/bone marrow transplants. Event-free survival (EFS) at 1 year for the 11 cases of B-ALL is 64% (95% confidence intervals [CI] 31-89%) and of 13 stage IV B-NHL cases is 50% (95% CI 19-75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13-68%) compared with 76% (CI 39 94%) for those without bulky abdominal disease. Overall EFS for eight CNS+ patients is 73% at 1 year (95% CI 34-97%) compared with 48% (95% 24-74%) for those without CNS disease (CNS-). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P less than 0.5). A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or 1 fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49-95%] versus 24% [6-65%], P less than 0.04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B-ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy. PMID- 2261347 TI - Alpha-2a-interferon/melphalan/prednisone versus melphalan/prednisone in previously untreated patients with multiple myeloma. AB - Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM. PMID- 2261348 TI - Measurement of fibrinogen binding to platelets in whole blood by flow cytometry: a micromethod for the detection of platelet activation. AB - Platelet fibrinogen binding in whole blood has been measured in vitro by flow cytometry using a commercially available, fluorescein isothiocyanate (FITC) conjugated polyclonal antifibrinogen antibody. Fibrinogen-antifibrinogen immune complexes were formed in experimental conditions approaching antigen-antibody equivalence, but optimal reaction conditions in which their formation was prevented or minimized could be achieved. Immune complex formation was associated with fibrinogen binding to unstimulated platelets but did not significantly affect ADP-induced fibrinogen binding. Half-maximal fibrinogen binding occurred at about 0.4 microM ADP, and ADP-induced fibrinogen binding continued progressively during 20 min incubation with 10 microM ADP. Fibrinogen binding correlated closely with platelet glycoprotein IIb-IIIa expression in members of a family with Glanzmann's thrombasthenia, and, in double labelling experiments, with the binding of PAC1, a monoclonal antibody that binds to GP IIb-IIIa only after the exposure of fibrinogen receptors. These studies show that platelet fibrinogen binding can be reliably measured in whole blood by means of a polyclonal antifibrinogen antibody which does not discriminate between plasma and platelet-bound fibrinogen, despite the presence of an approximately 100-fold excess of the former. PMID- 2261349 TI - Pretransfused patients with severe aplastic anaemia exhibit high numbers of cytotoxic T lymphocyte precursors probably directed at non-HLA antigens. AB - Patients with severe aplastic anaemia (SAA) have a relatively high risk of graft rejection after transplantation of bone marrow from HLA-identical siblings compared with patients transplanted for leukaemia. This is presumed to be due to pretransplant blood transfusions which sensitize the recipient's immune system to non-HLA antigens expressed on donor marrow cells. To test this hypothesis, we estimated in the peripheral blood of 18 SAA patients, the frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p) directed against mononuclear cells from syngeneic twins, HLA-identical siblings or HLA-matched unrelated individuals. The results were compared with the frequencies of CTL-p in 13 healthy subjects or leukaemia patients who had not been transfused. Pretransfused patients with SAA had significantly higher frequencies of CTL-p directed against HLA-identical siblings (P = 0.002), and against HLA-matched unrelated individuals (P = 0.004), than did untransfused individuals. In contrast, the frequency of CTL-p in two pretransfused patients against syngeneic mononuclear cells was very low. We propose that the increased numbers of CTL-p in the blood of pretransfused SAA patients are directed against non-HLA antigens on target cells and may be the result of prior blood transfusion. PMID- 2261350 TI - Abnormal tryptic peptide from the spectrin alpha-chain resulting from alpha- or beta-chain mutations: two genetically distinct forms of the Sp alpha I/74 variant. AB - Limited tryptic digestion of native spectrin (Sp) has revealed several variants in hereditary pyropoikilocytosis (HPP) and in a subset of patients with hereditary elliptocytosis (HE). In most cases, tryptic peptide corresponding to the alpha I (N-terminal) 80 kD domain is wholly or partially replaced by smaller fragments. These variants are provisionally designated according to the molecular weight of the most prominent new peptide. Partial amino acid sequences of the abnormal peptides and DNA analysis of the alpha-spectrin gene have shown that most variants result from substitution or insertion of an amino acid in the alpha I-domain. However, similar investigations did not detect any such abnormality in the spectrin alpha I-domain of an HE black kindred with one of the spectrin variants called Sp alpha I/74. In this kindred, restriction fragment length polymorphism studies and transmission of the genetic polymorphism relative to the alpha II-domain excluded the involvement of the alpha-chain in the pathological process. To ascertain whether the abnormal alpha I 74 kD peptide might be caused by a beta-chain mutation, we reconstituted hybrid dimers combining normal and HE Sp-chains. The tryptic peptide patterns of spectrin hybrid dimers containing HE alpha-chain and control beta-chain showed a normal 80 kD tryptic product. In contrast, the hybrid dimer containing normal alpha-chain and HE beta-chain gave rise to increased 74 kD peptide at the expense of the 80 kD, demonstrating that the mutation in this family resides in the beta-chain. The same method was used to show that in two other unrelated white kindreds, the elevated 74 kD peptide arose from a Sp alpha-chain defect. Thus an alteration in tryptic susceptibility within the N-terminal domain of the spectrin alpha-chain can be directed by a mutation in the beta-chain. The hybridization technique affords a definitive means of distinguishing between alpha- and beta-chain mutants. PMID- 2261351 TI - Effects of recombinant human erythropoietin on haemolytic anaemia in mice. AB - The effects of repeated administration of recombinant human erythropoietin (rHuEPO) were investigated in mice with haemolytic anaemia. Mice with haemolytic anaemia induced by phenylhydrazine (PHZ mice) were examined as an acute model and New Zealand black mice (NZB mice) at 13 months of age were examined as a chronic model. The plasma erythropoietin (EPO) level in PHZ mice was high and showed a strong inverse correlation with the Hb in the anaemia development period. However, it was relatively low in the recovery period from anaemia. On the other hand, the plasma EPO level in NZB mice showed a simple inverse correlation with the Hb. The rHuEPO was injected every day for a week into these mice. While a high plasma EPO level was maintained in PHZ mice, no significant effect was observed by injection with rHuEPO at dose of 600 IU/kg. However, in the recovery period from anaemia, RBC and haemoglobin in PHZ mice were increased by the rHuEPO treatment and recovered more quickly to their normal levels. In NZB mice, RBC and haemoglobin were also increased by treatment with rHuEPO at dose of 600 IU/kg. Anti-RBC autoantibodies and anti-EPO antibodies did not increase, while RBC and plasma EPO levels were increased by the rHuEPO treatment. These results suggest that some types of haemolytic anaemia are not always combined with high endogenous EPO levels and that exogenous rHuEPO may be effective for use in the treatment of haemolytic anaemia. PMID- 2261352 TI - Urinary autoantibodies against intrinsic factor in pernicious anaemia patients. AB - In radioimmunoassay seven concentrated urines of penicious anaemia (PA) patients were positive for intrinsic factor (IF). Four were studied by gel filtration. Two contained both binding and blocking antibodies against IF, one had only blocking antibodies and one lacked both types of antibodies. The antibodies were mainly of the IgG-type. No such antibodies were found in the urine of a healthy person. None of the urines studied contained enough protein to be classified as proteinuric. Not until the interferences of the autoantibodies in the IF assay can be eliminated is the assay of value in the diagnosis of PA. PMID- 2261353 TI - Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunit. AB - We have used the monoclonal antibodies 2A4 (specific for the H subunit of human ferritin) and LO3 (specific for the L subunit) for immunocytochemical detection of ferritin in bone marrow and peripheral blood cells from normal subjects and patients with various haematological disorders. Formalin-fixed slides were stained by the immunoalkaline phosphatase procedure (APAAP). In normal subjects, ferritin could be found only in bone marrow smears and appeared to be largely confined to erythroid precursors and reticuloendothelial cells. The more immature erythroid precursors contained higher concentrations of cellular ferritin. Although evaluation could be only semiquantitative, erythroblast ferritin appeared to be more reactive with the monoclonal 2A4 (15 +/- 7% positive erythroblasts) than with the monoclonal LO3 (6 +/- 5% positive erythroblasts), indicating that H-type ferritin was predominant, particularly in proerythroblasts and basophilic erythroblasts. By contrast, the ferritin present in reticuloendothelial cells appeared to be predominantly of L-type. Patients with iron deficiency showed low levels of positive erythroblast, whereas the reverse was true in patients with transfusional iron overload. Intense positivity for reticuloendothelial cell ferritin was found in patients with anaemia of chronic disease. In myelodysplastic syndromes and acute myeloid leukaemia (AML), ferritin positivity was generally very strong at any stage of erythroblast development, particularly with the monoclonal antibody 2A4. Perls-positive perinuclear granules of ring sideroblasts were not stained, confirming that mitochondrial iron deposition is not in the form of ferritin. In AML and myelodysplastic syndromes with excess of blasts, ferritin could be detected also in immature myeloid cells. These data indicate that: (a) in normal conditions ferritin is mainly expressed in red cell precursors and reticuloendothelial cells, and this is in keeping with the peculiar role of these cells in iron metabolism; (b) abnormal cell ferritin contents can be observed in both iron overload and malignancy. PMID- 2261354 TI - Hypoglycaemia and Hodgkin's disease. PMID- 2261355 TI - Control of steroid-resistant autoimmune haemolytic anaemia by cyclosporine. PMID- 2261356 TI - A variant congenital dyserythropoietic anaemia presenting as a fatal hydrops foetalis. PMID- 2261357 TI - Rapid detection of a Mediterranean beta (0) beta-thalassemic splice junction mutation by DNA amplification and BsaB1 mapping. PMID- 2261358 TI - Excess of monoclonal plasma cells in MGUS and diagnosis of early myeloma. PMID- 2261359 TI - Platelet heterogeneity and 111Indium labelling: possible interpretive artefacts in survival studies. PMID- 2261360 TI - Expression of natural killer antigens in a subset of 'non-T, non-B lymphoma/leukaemia with histiocytic features'. PMID- 2261361 TI - Who benefits from phase I studies? PMID- 2261362 TI - Minimal residual disease in leukaemia and lymphoma. PMID- 2261363 TI - The ultimate consultation in modern oncology. PMID- 2261364 TI - The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group. AB - We analysed the incidence of amenorrhoea and its association with outcome in a cohort of 1127 premenopausal women with breast cancer randomized to International Trial V (formerly Ludwig V). For 552 patients without axillary lymph node involvement, one course of perioperative cytotoxic drugs was compared with no adjuvant chemotherapy. For 575 patients with node-positive disease, a single course of cytotoxic chemotherapy was compared with a prolonged treatment (6 or 7 courses). Amenorrhoea was defined as having no menstrual bleeding for a 3-month interval within the first 9 months after surgery. Amenorrhoea was observed in 21% of the 199 patients with node-negative breast cancer who received no adjuvant therapy, 31% of the 353 node-negative patients who had a single course of cytotoxic therapy, 31% of the 188 patients with node-positive disease who had the same short-duration therapy, and 68% of the 387 node-positive patients who had a prolonged adjuvant therapy. Amenorrhoea was associated with an increased disease free survival (DFS) only in the patients with prolonged cytotoxic therapy: 4-year DFS % (+/- s.e.) was 68% +/- 3% vs. 61% +/- 5% for the amenorrhoea and the no amenorrhoea groups, respectively, (p = 0.05). In contrast, the comparison between prolonged therapy and one single course among node-positive patients showed a much larger treatment effect (4-year DFS 66% vs. 38%, p less than 0.0001). We conclude that although cytotoxics-induced amenorrhoea is associated with a better outcome, it is unlikely that this form of endocrine manipulation is the main mechanism of response to adjuvant systemic chemotherapy. PMID- 2261365 TI - Phase I-II constant infusion of adriamycin (doxorubicin) by ambulatory pump delivery system in heavily pretreated (including adriamycin) breast cancer patients. AB - Previous studies have shown that the protracted infusion of adriamycin (ADM) by the ambulatory delivery system can significantly decrease both the cardiac and hematological toxicity caused by intermittent bolus administration. We treated 27 patients with metastatic breast cancer who had been heavily pretreated with regimens including ADM. Treatment consisted of 15- or 25-day courses of ADM at a mean dose of 3.8 mg/m2 (2.2-4.5 mg/m2) infused by programmable portable pump. Early cardiac toxicity was detected by echocardiography-Doppler. Two-dimensional echocardiography made possible the detection of interventricular septum hypokinetics, an early sign of a decrease of systolic function of the left ventricle. Despite the very high cumulative dose of ADM (mean dose 777.79 mg/m2, range 282-1647 mg/m2) received by these patients, no clinical heart failure was observed. Most frequently observed complications were oral mucositis, Grade 2 and 3 (10 patients), and complications related to the drug delivery system (15/137 courses). Hematological toxicity was minimal. Seven Grade 2 and five Grade 3 (but no Grade 4) alopecia were observed. Objective response was obtained in four of 24 patients (17%) evaluated for response, (only 21 were fully evaluable): one complete response and three partial responses (duration: 6.6, 7 and 11 months, respectively). Stabilization was seen in 14 patients lasting three to 26 months. The performance status and symptoms of nine of the patients (37%) was significantly improved. Our results show that continuous infusion of ADM is well tolerated and provides palliation to patients with metastatic breast cancer. It merits a trial as first-line treatment. PMID- 2261366 TI - AIDS-associated non-Hodgkin's lymphoma in Italy: intravenous drug users versus homosexual men. The Italian Cooperative Group on AIDS-Related Tumors (GICAT). AB - Because of growing evidence that there are differences in the natural history of HIV infection in intravenous drug users (IVDU) and homosexual men, the clinicopathological features and response to treatment of AIDS-related non Hodgkin's lymphomas (NHL) were analyzed in 150 cases (96 IVDU and 31 homosexual men) by the Italian Cooperative Group on AIDS-related tumors. Twenty-three patients fell within other risk groups. The median age was 26 years for the IVDU and 38 for the homosexual men. Forty percent of patients in both of the risk groups manifested full-blown AIDS prior to development of the lymphoma. In both groups, most of the NHL were of high or intermediate type (IVDU 96%, homosexual men 86%). In high-grade NHL, Burkitt's type lymphoma was present in 40% of the homosexual men and in 29% of the IVDU (a non-significant difference), while an immunoblastic lymphoma was diagnosed in 46% of IVDU and 27% of homosexual men (non-significant). No oral localizations were observed, and one homosexual presented with a rectal lymphoma. Almost half of the patients (47%) received no antineoplastic treatment because of rapid disease progression or of diagnosis only at post-mortem. Intensive combination regimens administered in one-third of both IVDU and homosexual men (compared to CHOP or CHOP-like combinations) provided more CR (3/13 vs 3/24 in IVDU and 2/3 vs 1/7 in homosexuals), although the overall survivals with both the intensive and less intensive chemotherapy protocols remained similar. Overall, the median survival was 3.7 months for IVDU and 3.6 months for homosexual men. The most reliable predictors for survival were opportunistic infections at onset in IVDU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261367 TI - On the receiving end--III. Measurement of quality of life during cancer chemotherapy. AB - From previous studies of the side effects patients identified as important in cancer chemotherapy we identified eight groups of symptoms. Linear analogue self assessment (LASA) scales for these 8 items form a new instrument (GLQ-8) for measuring aspects of quality of life. Patients completed both GLQ-8 and five previously validated LASA scales, together with a new single global quality of life scale (GLQ uniscale) and the visual analogue version of the Spitzer QL Index. This analysis includes 166 patients, with 47 1-hr test-retest and 29 24-hr test-retest pairs. The new scales showed high reliability, with retest correlation coefficients exceeding 0.8 for all items except GLQ uniscale, appetite and anxiety on 1-hour retest, and all except nausea and numbness on 24 hour retest. Correlations were in general higher for the GLQ-8 items than for the 5 older LASA items, while inter-item correlations were lower. Comparisons of the new scales with established instruments and comparisons of new scale scores between known groups supported the validity of the new scales. We conclude that the GLQ-8 and GLQ uniscale are convenient and reliable instruments measuring aspects of quality of life in patients receiving cancer chemotherapy. PMID- 2261368 TI - Cancer incidence in European migrants to New South Wales. AB - The incidence of cancer in migrants to New South Wales (NSW) from Italy, Greece, Yugoslavia, Germany, the Netherlands, Poland and USSR has been compared with that in the Australian-born population using data from the NSW Central Cancer Registry for 1972-84. The indirectly age-standardized incidence ratios (SIR) in all seven countries were low for melanoma of skin and high for gastric cancer. Cancers of the colon, oesophagus and lip also tended to have low SIRs. Migrants from Italy, Greece and Yugoslavia had significantly less cancer at all sites than the native born Australians mainly due to low SIRs for cancers of colon, lung (except Yugoslavian-born men), prostate and, in men, 'head and neck' (excluding nasopharynx). Cancers of breast and testis were relatively less common in migrants from Italy and Yugoslavia. SIRs were high for cancers of bladder (in Italian-born men), liver (in Greek- and Yugoslavian-born men) and nasopharynx (in Greek-born men and Italian-born men and women). Amongst migrants from the four more northerly European countries, ovarian cancer was relatively more common in women from Germany and Poland as was bladder cancer in men, but not women, from Germany and the Netherlands. Cancers which had significantly increased SIRs in one migrant group only were lung (Dutch-born men), cervix uteri and body of uterus (German-born women), gallbladder and bile ducts (Polish-born women), thyroid (Italian-born women), connective and other soft tissue (Russian-born men) and brain (Greek-born men and women computed together). Lymphomas were relatively less common in men born in Yugoslavia. PMID- 2261369 TI - Effectiveness and low toxicity of hepatic artery infusion with fluorouracil and mitomycin for metastatic colorectal cancer confined to the liver. The Swiss Group for Clinical and Epidemiological Cancer Research (SAKK). AB - The usefulness of hepatic artery infusion (HAI) with floxuridine is limited by the severe biliary and hepatic toxicity of floxuridine. This prompted the SAKK to evaluate the effectiveness, toxicity and feasibility of HAI with fluorouracil (FU) and mitomycin (MMC) administered by an external portable pump. Of 28 patients treated, partial responses were obtained in 14 (50%, 95% confidence interval: 30% to 70%) and stabilization in 11 (39%, 21% to 60%), for a median duration of 12.6+ months. Median survival was 19.5+ months. Grade I-II toxicity (WHO) consisted of nausea (46%), leucopenia (32%) thrombocytopenia (21%) and abdominal discomfort (25%). Two patients developed gastro-duodenal ulcers and two others grade III leucopenia. No life-threatening side effects, especially no sclerosing cholangitis or chemical hepatitis, were observed. In conclusion, HAI with FU and MMC is a valid alternative to floxuridine HAI in metastatic colorectal cancer confined to the liver. PMID- 2261370 TI - Efficacy and side effects of two chemotherapy regimens with cisplatin plus fluorouracil in advanced squamous cell carcinoma of the head and neck. PMID- 2261371 TI - Encephalopathy with hyponatremia and inappropriate arginine vasopressin secretion following an intravenous ifosfamide infusion. PMID- 2261372 TI - Transcriptional control and cellular transformation. PMID- 2261373 TI - Prelude to breast cancer prevention with an antiestrogen. PMID- 2261374 TI - Adjuvant treatment of colon cancer: where to go from here? PMID- 2261375 TI - The clonogenic assay with human tumor xenografts: evaluation, predictive value and application for drug screening. AB - The feasibility, evaluation and predictive value of the colony-forming assay with human tumor xenografts for screening anticancer drugs have been studied. Using human tumors grown in serial passage in nude mice, adequate colony formation was observed in 215 of 251 (86%) different solid human tumors of various histologies. Based on in vitro growth characteristics, a quality-controlled assay protocol was developed. With the proposed criteria for standardized evaluation of individual experiments a substantial increase in assay reliability was achieved. The five clinically established agents, cisplatin, doxorubicin, etoposide, mitomycin-C and vindesine, were studied for anticancer activity in the clonogenic assay. Drugs were applied over a wide dose range by continuous exposure, yielding clear dose response effects with coefficients of correlation between r = 0.946 and 0.995. Relevant dose levels predicting correctly for the clinical efficacy of the agents were determined by comparison of in vitro anticancer activity to in vitro toxicity on human bone marrow as follows: cisplatin 0.1 micrograms/ml, doxorubicin 0.01 micrograms/ml, etoposide 0.1 micrograms/ml, mitomycin-C 0.005 micrograms/ml, vindesine 0.01 micrograms/ml. At these concentrations, clinically sensitive tumor types showed inhibition of colony formation in 99 of 240 cases (41%), whereas 11% (19/176) of clinically resistant tumors were responsive. The relevant dose levels used equal between 0.3% and 4.0% of the achievable peak plasma concentrations in man. The predictive value of the clonogenic assay was determined by treatment of the same tumors in vitro and in vivo in tumor-bearing nude mice. In 174/220 comparisons (79%), in vitro data predicted correctly for the in vivo sensitivity of the xenografted malignancies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261376 TI - Late cardiac effects after mantle radiotherapy in patients with Hodgkin's disease. AB - Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent cardiac testing with myocardial scintigraphy during exercise, Echo-Doppler cardiography and CT-examination, 10-20 years after treatment. Four of twenty-six (15%) young patients had serious cardiac complications after mantle therapy, and reduced systolic and/or diastolic function; and minor valvular disturbances were often found. One 36-year-old female died of myocardial infarction 4 years after therapy, one 39-year-old male had two non-lethal infarctions after 14 years, one 36-year-old male with no symptoms had severe reversible ischemia and three proximal coronary artery stenoses, and one 32-year-old female with constrictive pericarditis had pericardeictomy 14 years after therapy. In 23/24 patients the pericardial thickness was normal and no pericardial effusion was found. 23/24 patients had normal working capacity, but myocardial scintigraphy was normal in only 9 patients. 11/25 patients had reduced systolic function and in 12/24 patients the diastolic function was reduced. 11/25 patients had abnormal valvular or subvalvular structures. Valvular stenosis was not found but aortic, mitral and tricuspidal regurgitations were found in 1/25, 9/25 and 22/25, respectively. In all but two cases the regurgitations were mild. We conclude that mediastinal irradiation must be considered a risk factor for cardiac disease. It may be advisable to reduce other risk factors in these patients. PMID- 2261377 TI - High dose epirubicin in refractory or relapsed non-seminomatous testicular cancer: a phase II study. AB - Sixteen patients with metastatic nonseminomatous testicular cancer refractory to cisplatinum combination chemotherapy, were treated with epirubicin 100-120 mg/m2 q d 22. One partial remission lasting 6 months was achieved. Two additional patients had stabilisation of disease for 3 and 4 months. Median time to progression was 43 days. Myelosuppression was dose-limiting, with a WBC nadir of 1900/microliters. 4/30 cycles (13%) were associated with granulocytopenic fever. One patient developed a decline in cardiac ejection fraction without clinical signs of congestive heart failure. Epirubicin in this dosage and schedule has no major therapeutic activity in heavily pretreated non-seminomatous testicular cancer. PMID- 2261378 TI - Treatment of metastatic renal cell cancer patients with recombinant subcutaneous human interleukin-2 and interferon-alpha. AB - We treated 17 patients who had progressive metastatic renal carcinoma with a combination of subcutaneous recombinant human interleukin-2 (administered every 12 hours, at 9.0 million IU/m2 on days one and two, followed by 1.8 million IU/m2, five days per week, over six consecutive weeks) and interferon-alpha 2b (given at 5 million U/m2 three times weekly, for six consecutive weeks). Treatment courses were repeated in patients presenting with stable or regressive disease after the six weeks of combination therapy (11 of 14 evaluable). Two and three of 14 evaluable patients achieved complete and partial remissions, respectively. Toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (WHO) fevers, chills, malaise, nausea/vomiting, and anorexia in more than two-thirds of the patients treated. PMID- 2261379 TI - Randomized, double-blind cross-over study of acute cisplatin-induced nausea and vomiting, comparing a new schedule of the combination of metoclopramide and methylprednisolone versus metoclopramide alone. PMID- 2261380 TI - Dermal infiltrates of a lymphoma as a complication of implanted venous access catheter placement. PMID- 2261381 TI - An analysis of 12 cases of non-Hodgkin's lymphomas involving the testis. PMID- 2261382 TI - Salvage treatment for ovarian cancer. PMID- 2261383 TI - Stage II testicular seminoma: evolution of radiotherapeutic practice in the United States. AB - We studied the evolution of treatment philosophy for testicular seminoma, by means of a questionnaire mailed to radiation oncologists practising in the United States. Of the 600 respondents 65% indicated a change in treatment policy since 1982. In patients with stage IIA disease the mediastinum is no longer treated by 62% of physicians, whereas 38% omit such treatment in Stage IIB patients. A trend towards the use of lower doses of radiation in areas treated was also noted. Omission of mediastinal irradiation in some stage II patients may be associated with an increased risk of failure in this site. Patients who do not receive treatment to the mediastinum must be carefully followed for recurrent tumour. PMID- 2261384 TI - The value and significance of routine urine cultures in patients referred for radiation therapy of prostatic malignancy. AB - Radiation therapy of the prostate requires a simulator visit when a urinary catheter and rectal balloon are used for field determination. Radiation changes combined with the previous instrumentation, surgery and therapy makes diagnosing urinary tract infection (UTI) difficult. For this study a UTI was defined as the isolation of the same organism(s) at any concentration in two of three sequential urine samples. Urine cultures were obtained prior to radiation therapy (during and after the simulator visit) and while receiving radiation treatments. The study of 291 patients revealed a UTI in 20 (6.9%) prior to undergoing simulator evaluation and in an additional 13 patients at the first visit after to give an incidence of 11.34% prior to receiving radiation. The bacterial isolates in the 13 patients were more suggestive of reactivated chronic infection than catheter associated UTI. During radiation therapy approximately 1%-2% of patients developed a UTI per week. This study justified the use of routine urine cultures in these patients and suggests that further investigations should be done to reduce the incidence of infections occurring both prior to and during radiation therapy. PMID- 2261385 TI - Conservation of the breast using two different radiotherapy techniques: interim report of a clinical trial. AB - Patients with a clinically palpable breast carcinoma, 4 cm or less in diameter, and with no palpable nodes in the axilla were prospectively entered into a randomized clinical trial. A total of 713 patients were registered between November 1982 and December 1987, of whom 708 are evaluable at a median follow-up of 37 months. Following excision of the primary tumour, patients were randomly allocated either to have radiotherapy to the affected quadrant only (LF group) or to the whole breast and regional lymph node areas (WF group). No adjuvant hormone or chemotherapy was prescribed. The primary tumour was reported as completely excised histologically in 80% of cases, incompletely excised in 10%, and no estimate was possible in 10%. At six years from first randomization, 96% of the WF group and 92% of the LF group have remained free of breast recurrence (94% and 87% actuarial breast recurrence-free survival at 5 years). Part of the difference may be explained by the 20% recurrence rate in the breast for lobular carcinomas treated within the LF group. Of the WF group 14 patients (4%) developed recurrent disease in the axilla, compared to 50 patients (14%) in the LF group (95% and 86% actuarial axillary recurrent-free survival at 5 years). Patients with primary tumours histologically 1 cm or less in diameter had a 98% actuarial 5-year survival compared with 74% for those with tumours measuring 2 cm or more in diameter (P = 0.003). Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence. PMID- 2261386 TI - A possible role for ultrasound of the axilla in staging primary breast cancer. AB - The axillae of 30 patients with primary breast cancer (Stage I and II) were prospectively examined in this pilot study using ultrasound. No patient had palpable axillary lymph nodes on clinical examination. Treatment had involved wide local excision, but no prior form of surgical dissection had been performed on the axilla. Using the contralateral axilla as an internal control, lymph nodes were observed in the ipsilateral axilla alone on ultrasound in 8/30 patients (27%). Following radical irradiation of the breast and local lymph drainage areas, 2/8 patients of the group with observed lymph nodes have relapsed, one with systemic disease and the other with local recurrence in the breast, after a minimum follow-up of 12 months. No patient without observed nodes has recurred. This difference does not reach statistical significance. This technique merits further investigation as an adjunct to current staging procedures for early breast cancer. PMID- 2261387 TI - Ewing's sarcoma in adults. PMID- 2261388 TI - A randomized trial comparing whole abdominal radiotherapy with chemotherapy following cisplatinum cytoreduction in epithelial ovarian cancer. West Midlands Ovarian Cancer Group Trial II. AB - The potential role of consolidation therapy has been tested in a randomized trial in ovarian cancer. Patients were randomized to receive either whole abdominal radiotherapy using the moving strip technique (n = 56) or one year of chlorambucil (n = 53) following primary surgery, five courses of cisplatinum 100 mg/m2, and second look laparotomy. Overall survival at two years was 35%. There was no significant difference in survival between the two groups, and in spite of the observation that approximately 50% of the patients were optimally debulked prior to consolidation, no subgroups in either arm could be identified who might benefit from consolidation therapy. Toxicity was considerable in both arms, and almost 50% of patients were unable to complete the planned treatment in both arms. These results suggest that after primary surgery and cisplatinum chemotherapy, there is no indication for consolidation therapy with either radiotherapy or alkylating agents. PMID- 2261389 TI - The radiological assessment of adults with soft tissue sarcoma. PMID- 2261390 TI - Cutaneous neuro-endocrine (Merkel cell) carcinoma. AB - Two cases of neuro-endocrine (Merkel cell) tumours of the skin are reported. There was evidence of distant relapse in both patients who eventually succumbed to the disease. The wide range of clinical and radiological manifestations of this rare tumour are discussed and the literature reviewed. PMID- 2261391 TI - Hodgkin's disease in two sisters. AB - The case histories of two sisters with Hodgkin's disease are reported. Although the disease developed at different ages, the clinical presentation was similar and the histological classification of biopsy material was identical in the two cases. The relative importance of genetic and environmental factors in the aetiology of the disease is discussed. PMID- 2261392 TI - The management of osteosarcoma in adults. PMID- 2261393 TI - Approaches to breast cancer prevention. AB - It may be possible to delay the step-by-step progression towards frank invasive cancer by avoiding one or more of the well-known clinical risk factors. In addition current clinical trials in the USA and Europe are assessing whether the use of tamoxifen, vitamin analogues or a low-fat diet can delay the appearance of overt disease in women known to be at high risk, but it will be several years before such trials can be evaluated. For women seeking advice on prevention, non toxic supplements to the diet such as beta-carotene, vitamin A analogues or selenium compounds, and the avoidance of alcohol and obesity, are examples of practical advice which can do no harm yet may help to protect against breast cancer development. In the case of the very anxious first degree relative of a breast cancer patient, the current choice lies essentially between regular monitoring, mastectomy with reconstruction, early termination of ovarian activity and anti-oestrogen therapy. Currently, considerable research is being directed towards identifying oncogenes and growth factors which are involved in the growth of breast cancer. In the meantime, more research needs to be devoted to the effect of various progestagens in counteracting oestrogen support of breast cancer growth, and to biological observations on different formulations and doses of combined oestrogen/progestagen preparations which may reduce breast cancer risk both in pre- and postmenopausal women. PMID- 2261394 TI - Prader Willi syndrome and testicular tumour. PMID- 2261395 TI - Strontium-90 for conjunctival AIDS-related Kaposi's sarcoma: the first case report. AB - AIDS-related Kaposi's sarcoma is often treated by local therapy for physically or cosmetically disabling symptoms. We present the first case of a bulbar conjunctival Kaposi's sarcoma lesion to be treated with a strontium-90 ophthalmic applicator. The treatment is simple, effective and well tolerated and we recommend that it should be considered for the management of superficial Kaposi's sarcoma lesions of the conjunctiva. PMID- 2261396 TI - Pseudomyxoma peritonei treated by radiotherapy. AB - Pseudomyxoma peritonei (PP) is a rare condition. Treatment is usually unsuccessful and the prognosis is poor. This report describes a patient who survived 16 years following their initial presentation. PMID- 2261397 TI - Cervical cancer in young women in Northern Ireland: 1970-1985. AB - From 1970 to 1985, 109 patients under 35 years of age developed invasive cervical cancer in Northern Ireland (NI). Information on incidence, staging, histology, primary treatment and survival was collected retrospectively and results compared with a community-based sample of all age groups from the West Midlands of England. Incidence increased in NI over the study period. Young patients presented with early stage disease, typical histology and had a stage for stage outcome similar to the all age groups. NI results do not demonstrate more aggressive disease in the under 35s. PMID- 2261398 TI - Radical radiotherapy for carcinoma of the anal canal. AB - The treatment of squamous cell carcinoma of the anal canal remains controversial, and recent reports have recommended combined chemotherapy and radiotherapy rather than radiotherapy alone as primary treatment. In order to define the role for more aggressive local therapy we have performed a retrospective analysis on patients with squamous cell carcinoma of the anal canal treated at the Royal Marsden Hospital between 1958 and 1986. Among 42 patients who received radical radiotherapy (RRT) the overall 5-year caused specific survival (CSS) was 52%. Tumour stage and node involvement were the most important prognostic factors. The 5 year CSS were T1 100%, T2 59%, T3 40% and T4 0% (P less than 0.05). The 5-year CSS for node-negative patients was 64% compared to 23% for node-positive patients (P less than 0.095). A minimum tumour dose of 60 Gy in 30 fractions over 6 weeks was essential to achieve local control and was associated with minimal late morbidity and with the retention of anal continence in all patients locally controlled. PMID- 2261399 TI - Stage I glottic carcinoma: an analysis of tumour recurrence after primary radiotherapy. AB - During the period 1978-82, 145 patients with Stage I glottic carcinoma had primary radiotherapy at the Finsen Institute in Copenhagen. Of these, 35 patients developed recurrence, corresponding to a local control rate of 76%. Following salvage surgery a further 14% of the patients became free of disease for a minimum follow-up of 3 1/2 years or until death. A total local control rate of 90% was obtained. Possible prognostic factors in patients developing local recurrence following radiotherapy were assessed. No reliable predictor of treatment failure could be identified: sex, age, haemoglobin concentration, smoking and drinking habits, tumour stage, location, size and differentiation, were all found to be of no significance. PMID- 2261400 TI - Cranial nerve involvement by nasopharyngeal carcinoma: response to treatment and clinical significance. AB - The incidence of cranial nerve involvement in a group of 564 patients with nasopharyngeal carcinoma was 12%. Most of these patients had multiple cranial nerve involvement with the fifth and sixth nerves being most commonly affected. Different cranial nerves had different chances of recovery after radiotherapy. About half the patients with cranial nerve palsies had complete neurological recovery after radiotherapy. The cranial nerve response, however, was not a significant predictor of local tumour control. PMID- 2261401 TI - Tumour markers in breast cancer: a report on the extensive clinical use of B5 and CA15.3. AB - The B5 antigen is an integral component of human erythrocyte membranes which becomes enhanced in cancer patients. Here we have measured the correlation between B5 status and disease status in 456 patients with breast cancer. A B5 positive status was found in 45/335 (13%) of patients who were long-term disease free and without recurrence (group A), and in 12/53 (23%) of patients who were disease-free following recurrence (group B). In contrast, the majority of patients with progressive disease were B5 positive, including 27/41 (66%) with progressive relapsed disease (group C) and 21/27 (78%) whose disease was progressive from diagnosis (group D). In a similar analysis of CA15.3 in 289 patients, abnormally high marker levels were found in 1/210 group A; 1/35 group B; 20/29 group C; and 8/15 group D patients. Changes in B5 level showed a high correlation with disease behaviour: rising B5 levels occurred in 56 patients, of whom 50 (89%) were found to have recurrent disease. A decrease in B5 was associated with remission in 53/55 (96%) patients. CA15.3 is a marker for breast cancer which related to tumour bulk, and combination of CA15.3 with B5 increased sensitivity for active disease as 21/24 (88%) of patients with recently relapsed disease were positive for either B5 or CA15.3: 16/24 (67%) of these patients had a positive marker result at, or prior to, clinical diagnosis of their recurrence. Overall, the combined use of CA15.3 and B5 gave clinically relevant data which was more informative than either marker alone. PMID- 2261402 TI - How many tests are required in the diagnosis of palpable breast abnormalities? AB - Palpable breast nodules in 143 patients attending our primary diagnosis breast clinics were assessed by clinical examination, needle cytology, mammography, ultrasonography and magnetic resonance imaging (MRI). The diagnostic accuracy of all test combinations was compared with the final diagnosis of malignant or benign disease. Two-test combinations increased the sensitivity of diagnosis over that of the individual tests to between 93% and 100% except for MRI/mammography and MRI/cytology. The combinations of three or more tests increased the sensitivity further, but at the expense of an increased false-positive rate. MRI does not appear to have an important role in the primary diagnosis of breast cancer. Mammography is necessary because of the possibility of occult or multifocal disease. Clinical examination was associated with a high false positive rate. The combination of cytology and ultrasound was best at correctly diagnosing malignancy, but in this series only 42% of patients underwent ultrasound examination. The role of breast ultrasound together with needle aspiration cytology for the diagnosis of malignancy in palpable breast nodules deserves further evaluation. PMID- 2261403 TI - Chemotherapy of breast cancer in Nigerians: side-effects and quality of life. AB - Fifty-seven breast cancer patients under follow-up between 1987 and 1988 at the Radiotherapy Department, Lagos University Teaching Hospital following mastectomy and radiotherapy were given combination chemotherapy as adjuvant therapy or as a result of recurrent disease. With the use of a detailed questionnaire the side effects and reactions to chemotherapy were assessed. Apart from disturbances of menstruation in 24 (53.3%) of the 45 premenopausal patients, the majority of patients tolerated treatment very well, whilst the side-effects that occurred were limited. Nigerian women may be more tolerant to the side-effects of chemotherapy than those women living in developed countries. PMID- 2261404 TI - Percutaneous nephrostomy: its value in obstructive uropathy complicating carcinoma of cervix uterus. AB - Percutaneous nephrostomies (PCN) were performed in 25 patients with uterine cervical malignancy between November 1982 and December 1987 at the Christie Hospital and Holt Radium Institute. Group 1 consisted of eight patients with untreated disease; group 2 consisted of eight cases with recurrent tumour; and group 3 consisted of nine patients with obstructive uropathy related to previous treatment. Six patients in group 1 subsequently received radical radiotherapy, and two of them were alive and disease free (33%) ten months later. Further active treatment was only possible in two of the patients with recurrence and overall median survival was only 51 days. All patients in group 3 had normalization of their renal function post-nephrostomy and prior to definitive management of the obstruction. We conclude that the technique should be considered in patients who had no previous treatment and in patients with treatment-related complications. Its value in recurrent disease is limited. PMID- 2261405 TI - Radiation therapy for symptomatic vertebral haemangioma. AB - Vertebral haemangiomas are slowly growing benign tumours and are usually asymptomatic. They rarely cause symptoms and signs related to cord compression. Larger lesions create significant problems during surgery because of haemorrhage and vascular supply crucial to spinal cord function. In such severely symptomatic vertebral haemangiomas, radiation therapy has been tried and good results obtained, especially in terms of good functional recovery. We have treated 17 patients (including nine paraplegic patients) with radiotherapy (Co-60). Treatment was given by single posterior field, encompassing the involved area with a dose of 35-40 Gy in 3 to 4 weeks (five fractions per week). All patients with pain and tenderness were relieved completely (87.5%) or partially (12.5%). Similarly patients with numbness and paresis showed either complete (66.7%) or partial response (33.3%) from symptoms on follow-up. Out of nine paraplegic patients six (66.6%) had recovered completely, one (11.2%) partially and two (22.2%) had no response. The two patients who did not show any marked relief, had paraplegia of longer duration (more than 6 months). Our study indicates that severely symptomatic vertebral haemangioma can be successfully treated by radiation therapy and it can be chosen as first line of treatment with an optimum dose of 35-40 Gy in 3 to 4 weeks. PMID- 2261406 TI - Problems in the management of testicular seminoma associated with a horseshoe kidney. AB - Four patients with seminoma of the testis and coexisting horseshoe kidney are presented. Three patients had stage one disease, which would conventionally be managed by abdominal nodal irradiation. However, because of the risk of radiation nephritis, a surveillance policy was adopted with regular computed tomography (CT). Two of these three patients have relapsed and are disease free after chemotherapy. The fourth patient had Stage IIC disease which initially responded to combined radiotherapy and chemotherapy. This patient's disease relapsed and he died despite further treatment. Because of the altered retroperitoneal anatomy, CT interpretation must be made with special care. PMID- 2261407 TI - Developments in surgical oncology: induction (neoadjuvant) chemotherapy--the state of the art. AB - The three established modalities for treatment of cancer are operative surgery, radiotherapy and chemotherapy. In the past, patients have been referred to clinics where experts in the appropriate discipline have usually advised management by one or other of the three modalities. In recent years it has become apparent that for some cancers in which good results have not been forthcoming by one therapeutic modality alone, improvements may well be made by integrating management using two or three forms of treatment, in a planned approach. Management of localized cancers in which a surgical operation is likely to play a major part has traditionally been carried out by surgeons. However, operative surgery alone may not provide optimal care so that surgical oncology has developed as a discipline often embracing combined treatment with either chemotherapy or radiotherapy or both. In managing advanced but localized cancers for which a surgical operation alone is unlikely to produce tumour eradication (or for which tumour eradication can only be achieved with a mutilating operation such as amputation) it has become increasingly recognized that reduction of tumour size and viability by using chemotherapy first may render many tumours more susceptible to total eradication by subsequent radiotherapy and/or surgical operation. Such treatment is often referred to as 'induction' or 'neo-adjuvant' chemotherapy. This paper summarizes the principles of use of induction chemotherapy with integrated follow-up radiotherapy and/or surgical operation. PMID- 2261408 TI - Pulmonary blastoma. AB - Pulmonary blastoma (PB) is the least common malignant pulmonary neoplasm, with less than 100 reported cases. This tumour occurs up to three times more commonly in males. There exists an age peak in the third and fourth decades, although approximately one quarter of cases occur in children, often in association with congenital lung disease. Although the clinical features of PB are not specific, the histopathological appearance is distinctive, showing an admixture of both epithelial and mesenchymal (sarcomatous) elements. Historically, surgery has been the most commonly used modality for localized disease: however, useful data on local control rates are lacking. Extrathoracic metastases are the major cause of treatment failure in PB, with chemotherapy having little impact in this disease. The role of radiation therapy in the management of PB has not been established, however, early radioresponsiveness was demonstrated in the palliative treatment of soft tissue and bone metastases in the case presented: radiation therapy should be considered in the management of this disease. PMID- 2261409 TI - Solitary choroidal metastasis in bronchial carcinoma. AB - Choroidal metastases, although uncommon, are a well-recognized complication of malignant disease and their development is usually associated with other soft tissue metastases and a poor prognosis. About one-third of choroidal metastases arise from carcinoma of the bronchus. They are rarely solitary. Histologically confirmed solitary choroidal metastasis from squamous carcinoma of the bronchus has not been previously reported in the literature. We describe such a case. PMID- 2261410 TI - Depigmentation after carboplatin (Paraplatin) PMID- 2261411 TI - Lower hemibody irradiation. PMID- 2261412 TI - Heat and cancer therapy. PMID- 2261413 TI - Adenocarcinoma from an unknown primary presenting in women with an axillary mass. AB - Adenocarcinoma from an unknown primary is generally associated with a poor prognosis. This is not the case with women who present with disease confined to one axilla, when the primary, despite negative investigations, is often found to lie in the ipsilateral breast. Twenty such patients presented to our department between 1977 and 1989 and were generally treated by radical radiotherapy to the breast and peripheral lymphatics. Local control was achieved in the axilla in 17 of the 20 patients (85%). No primary has appeared in the breast, although one patient has died of a carcinoma of the colon. The 5-year actuarial survival of the group is 66%, similar to stage II breast carcinoma patients. The value of radiological and histopathological investigations is discussed. The cosmetic results are good and in view of the excellent local control achieved by irradiation we feel mastectomy is unnecessary in this rare presentation of breast cancer. PMID- 2261414 TI - A comparison of remote afterloading and manually inserted caesium in the treatment of carcinoma of cervix. AB - Between 1982 and 1985, 240 patients with carcinoma of cervix were treated by radical radiotherapy, 140 using the selectron at the Royal Beatson Memorial Hospital (RBMH) and 100 with conventional caesium at the Western Infirmary. To allow for the increased dose rate to point A (1.2-1.4 Gy/h) during selectron treatment the overall intracavity dose was reduced by a mean value of 25%. Local recurrence rates were similar: 15% (selectron) against 14% (conventional). Three year survival with local control was somewhat worse in the selectron group (77% against 81%) mainly because of an increased frequency of metastatic disease with local control (19.3% against 12.0%. The use of remote afterloading has not increased late morbidity (15.7% selectron, 15.0% conventional). The introduction of the selectron has brought about a marked reduction in staff radiation exposure. At the RBMH the mean recorded dose to nurses fell from 19 mSv in 1981 to 2.4 mSv in 1985. PMID- 2261415 TI - OC125 immunoscintigraphy in ovarian carcinoma: a comparison with alternative methods of assessment. AB - The membrane bound, tumour associated antigen CA125 is recognized by the monoclonal antibody OC125 and may be detected in tumour tissue and serum in over 80% of patients with epithelial ovarian carcinomas. A total of 13 immunoscintigrams using 111 MBq 131I-OC125 have been performed in 11 patients. The results have been compared with clinical examination, CT and ultrasound scans, surgical findings and serum CA125 concentrations. Macroscopic disease was present at the time of scanning in 11 patients (less than 2 cm, eight patients, greater than 2 cm, three patients). Clinical examination and ultrasound were positive in three, CT scanning in four, immunoscintography in seven and serum CA125 in eight patients. This pilot study suggest that serum CA125 estimation is the most sensitive indicator of disease activity. However, immunoscintigraphy using this agent may localize residual disease when clinical examination and other radiological investigations fail. PMID- 2261416 TI - Long-term survival after chemotherapy with cisplatinum, adriamycin and cyclophosphamide for carcinoma of the ovary. AB - Forty six patients with FIGO Stage II, III, and IV ovarian cancer received treatment with cisplatinum, adriamycin and cyclophosphamide. After a minimum follow-up time of 60 months 13 patients remain free of recurrence. The overall 5 year survival is 39% and the median survival is 39 months. The 5-year survival for Stages II, III, and IV is 64%, 40% and 0% respectively. The 5-year actuarial survival for those who had less than 2 cm residual disease (including those with complete debulking) is 72%, while for those who had greater than 2 cm residual disease (including those who had biopsy only) is 15%. None of the patients have developed any second neoplasm. PMID- 2261417 TI - Arteriovenous malformations of the brain: outcome of conventional radiotherapy in the management of 33 cases. AB - Thirty three patients with inoperable arteriovenous malformations of the brain received conventionally fractionated megavoltage photon radiotherapy. The dose varied between 30.00 wand 50.00 Gy with a median of 40.00 Gy. Treatment was not associated with any significant morbidity. Follow-up ranged from 16 months to 148 months, with a median of 79 months. The projected 5-year survival is 92% and rebleed-free survival 78%. There was a trend of increased bleed-free survival for doses greater than 46.00 Gy. PMID- 2261418 TI - Glottic cancer: results of treatment with radiotherapy in air and hyperbaric oxygen. AB - This paper is a retrospective analysis of 397 patients with glottic cancer, in which 240 patients were treated in air, and 157 patients in a hyperbaric oxygen chamber (HBO). The three principal dose/time schedules in air and HBO are contrasted, and shown to be iso-effective. The local tumour control rates show a significant improvement in favor of HBO: Stage I, 10%; Stage II, 37%; Stage III, 73%. Morbidity rates are explored, and suggest that the increased local control rate is not attained at the cost of an increased morbidity rate. The planning of the treatment, the preparation of the patient, and any subsequent complications are described. Treatment in the HBO chamber in a busy department has been shown to be a safe and routine procedure. PMID- 2261419 TI - Acute radiation pneumonitis after postmastectomy irradiation: effect of fraction size. AB - Prior to 1982 the standard radiation tissue absorbed dose administered to the chest wall following mastectomy was 40.0-42.5 Gy in 10 alternate day fractions over 4 weeks. From 1982 the standard maximum dose was 45.0 Gy administered in 20 daily fractions over 4 weeks. On review of the records of the 770 patients treated between 1979 and 1984, 19 (2.5%) had symptoms of acute radiation pneumonitis, 7/484 (1.4%) treated by the earlier technique and 12/286 (4.2%) by the later technique (X2 = 4.56, P less than 0.05). The mean 4 cm depth doses on the chest wall were 33.98 Gy and 36.84 Gy respectively in the earlier and later populations (t = 5.06, P less than 0.001) and 33.62 Gy and 38.30 Gy in those developing acute pneumonitis. Comparison of these two schedules gives an alpha/beta ratio of 8.5 Gy. It is suggested that the sparing of symptomatic acute reactions in human lung by smaller doses per fraction may be less than currently believed. PMID- 2261420 TI - Malignant lymphomatous polyposis: diagnosis and response to chemotherapy. AB - Malignant lymphomatous polyposis is a low-grade lymphoma with aggressive features. It may mimic polyposis coli on a barium enema and colonoscopic examination. An histological diagnosis may be made from a tissue biopsy taken via the colonoscope. We discuss the methods of diagnosis, the clinical behaviour and response to chemotherapy. PMID- 2261421 TI - The 'urn' portal; an alternative to the 'mantle' portal in the chemoradiotherapy management of paediatric Hodgkin's disease. AB - The experience of St Bartholomew's Hospital with a less than full mantle radiation field in the treatment of 31 children with clinically staged Hodgkin's disease is reported over a ten year period (1977-1987). The major indication for this portal was initial bulk, or residual disease after chemotherapy. Primary treatment consisted of radiotherapy alone (two children) or in combination with chemotherapy (29 children). An 'Urn' radiation portal has been used to encompass mediastinal and neck nodes, but with the aim of reducing radiation doses to lung, breast, axilla, lateral end of clavicle and humeral head. More recently, a further modification has employed partial heart shielding when anthracyclines have been part of the chemotherapy schedule. The majority have received 35 Gy in 20 fractions over 4 weeks with 4-6 Mv photons, and no child received in excess of 35 Gy to the mediastinum. An overall 5-year actuarial survival of 85% was achieved, and a 5-year relapse-free survival of 77%. Seven relapses and five deaths have been reported, all of which occurred in children who presented with nodular sclerosing histology. Six children relapsed within the radiation portals, and one with systemic disease alone. Only a single child relapsed in the unirradiated axilla, and this simultaneously with cervical, mediastinal and paraortic nodes. To date no second malignancies have been reported. PMID- 2261422 TI - The neuroleptic malignant syndrome. AB - The neuroleptic malignant syndrome is a serious and potentially fatal complication of neuroleptic and other dopamine antagonist drugs that are commonly used in symptom control in advanced cancer. Its true incidence is underestimated. Diagnosis may be difficult as its presentation may mimic infection or advancing malignant disease. PMID- 2261423 TI - Questions in the management of seminoma. PMID- 2261424 TI - The value of cervical cytology in detecting recurrent squamous carcinoma of the cervix postradiotherapy. AB - Twenty-six patients with central recurrent squamous carcinoma of the cervix following radiotherapy were identified from hospital records, 22 of which had cervical smears available for review, and are described here. As a second part to this study the cervical cytology results for 1987 and 1988 were compared with the clinical findings and eventual outcome. From a total of 384 smears in 1987 and 1988 there were 11 correctly identifying recurrence. Two smears, however, were false positive and two false negative. The overall sensitivity was 85% with a specificity of 99.5%. In addition three microscopic, operable recurrences were identified by cytology. In experienced hands routine smear cytology postradiotherapy is a reliable and useful addition to surveillance. PMID- 2261425 TI - Carcinoma of the cervix in women up to 35 years of age. AB - 50 women aged up to 35 years were diagnosed as having carcinoma of the cervix in Brighton, England between 1980 and 1985. The overall 5-year actuarial survival was 65% and 73% for stage IB. The 5-year survival for those aged 29 years or less was significantly worse than for those aged between 30 and 35 years, 39% versus 80%. There was a higher incidence of advanced stage and high-grade tumours in the younger women. It is suggested that the natural history of the tumour in women under 30 years is shorter than that in older women, and this is likely to be associated with high-grade, rapidly advancing carcinomas of poor prognosis. PMID- 2261426 TI - Influence of microscopic residual disease on survival for stage IB and IIA carcinoma of the cervix following intracavitary irradiation. AB - From 1977 to 1982, 102 patients with Stage IB and IIA carcinoma of the cervix underwent preoperative intracavitary caesium irradiation followed by radical hysterectomy and pelvic lymphadenectomy at the Wessex Radiotherapy Centre. The actuarial 5-year survival rate for Stage IB is 80% and for Stage IIA is 62%. Patients who had microscopic residual disease in the hysterectomy specimen and negative nodes showed an actuarial 10-year survival rate of 62% as opposed to 82% in patients with no residual disease and negative nodes (P less than 0.05). PMID- 2261427 TI - Second malignancies following radiotherapy for testicular seminoma. AB - Traditional treatment for testicular seminoma produces excellent survival. We report five, second non-testicular malignancies which occurred in a group of seminoma patients. A total of 79 men with primary testicular seminoma were available for analysis. All underwent a radical inguinal orchiectomy. Those with Stage I disease received adjuvant radiation therapy to the para-aortic and ipsilateral iliac nodes. The usual dose was 2500 cGy in 15 treatments. Stage II patients also received prophylactic mediastinal radiation therapy to a dose of 2500 cGy. None of the 51 Stage II patients died of tumour, whereas four of the 28 Stage II patients died of their disease. The median follow-up was ten years (range 4-25 years). The second malignancies seen were melanoma (2), myeloma, caecal adenocarcinoma, and retroperitoneal fibrosarcoma. All but one tumour developed within the radiation fields. Based on US SEER data for white males, only 1.5 cancers were expected, giving significantly greater (P = 0.04) relative risk. This observation lends support to observation, rather than elective treatment, in patients with Stage I testicular cancer. PMID- 2261428 TI - Mucosal melanomas of the head and neck: The Scottish experience. The Scottish Melanoma Group. AB - A retrospective analysis of malignant melanoma of the upper aerodigestive tract treated in Scotland between 1976 and 1988 has been performed to define the incidence, clinical features and response to treatment. Using the Scottish Melanoma Group database and pathology and oncology department registers 32 patients, 20 female, 12 male, were identified, representing a population incidence of approximately 0.5 per million per year. The median age was 69 years, range 38-86. Tumour arose in the nose or sinuses in 23 cases and the oral cavity or pharynx in eight cases. Metastases were present at presentation in four cases. Radical treatment was attempted in 27 patients: radiotherapy alone in 13, surgery alone in 10 and combined modality treatment in four. Complete regression, which was sustained in five cases, occurred in eight of the 13 radically irradiated patients; whereas sustained local control was achieved by radical surgery in only four of ten patients. The median survival is 14 months, non lived more than 63 months. Only one patient is alive and disease free, three more survive with disease. Of the 28 who had died, nine had local tumour only, nine metastases only and ten both local and distant disease. Outcome was not affected by age, sex, primary site or nodal spread. PMID- 2261429 TI - Treatment of non-melanoma skin cancer: a review of recent trends with special reference to the Australian scene. AB - Non-melanoma skin cancer (NMSC) is rarely recorded in cancer registries and it is only relatively recently that the serious public health implications, especially in terms of morbidity and expense, have been appreciated. Increased recreational sun exposure (particularly among the young) and ozone layer depletion have generated concern in many countries. Histological confirmation of the diagnosis, either by excision biopsy or punch biopsy is essential if management of the condition is to be rational and the results assessed. Surgery or radiotherapy or other dermatological techniques will cure over 90% of all NMSC. Comparison of the results of various modalities is difficult and poorly documented. Local recurrence rates of 2.0% for surgery and 3.7% for superficial X-ray treatment (SXRT), with 96% and 90% 5-year failure-free-survival respectively are reported from the Peter MacCallum Cancer Institute. More comparative trials are required with good cosmetic and late normal tissue damage evaluation. Factors affecting modality choice trends in Australia are discussed, where the role of plastic surgery has considerably expanded. The indications for radiotherapy and its fractionation require clarification, as does the use of moulds and implants. The belief that solar keratoses transform to invasive cancer has been seriously brought into question by recent Australian epidemiological studies. There can, however, be little doubt of the fact that keratoses are markers of cumulative solar damage, which is a well recognised risk factor for development of NMSC. There is a move away from aggressive ablative treatment of keratoses. The management of keratoacanthoma (KA) by observation is the usual practice, although radiotherapy is occasionally used when the lesion is conspicuous and unsightly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261430 TI - Extradural metastases in a case of medulloblastoma. AB - Extradural metastases in medulloblastoma appear to be rare. We describe a case associated with use of a lumbar drain and propose that in this situation, adjuvant chemotherapy and possibly extension of the radiotherapy field to include the entire sacral epidural fat-space to the lower border of S5, should be considered. PMID- 2261431 TI - Nasoethmoidal adenocarcinoma in woodworking twins. AB - The occurrence of nasoethmoidal adenocarcinoma in twins has not previously been reported. This paper describes the concurrent presentation in twins over 50 years after their first occupational exposure to hardwoods. There was a remarkable similarity in presentation. PMID- 2261432 TI - Regional Anesthesia. Subject and author indexes. Volumes 1-15, 1976-1990. PMID- 2261433 TI - Structure of the rat gene encoding cholesterol 7 alpha-hydroxylase. AB - Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is a microsomal cytochrome P-450 that catalyzes the first and rate-limiting step in bile acid biosynthesis, the major catabolic pathway in cholesterol homeostasis. The gene encoding the rat 7 alpha-hydroxylase has been isolated and characterized. Southern blotting experiments demonstrated that the gene is present in a single copy in the rat genome. DNA sequence analysis showed that the 7 alpha-hydroxylase gene is unique among the characterized cytochrome P-450s in that it contains only six exons. Nuclease S1 and primer-extension mapping experiments positioned the 5'-ends of the 7 alpha-hydroxylase mRNA approximately 20-25 nucleotides downstream of a consensus TATAAA sequence. RNA blotting experiments demonstrated the presence of multiple 7 alpha-hydroxylase mRNAs that differ in the lengths of their 3' untranslated regions. PMID- 2261434 TI - The nucleocapsid protein isolated from HIV-1 particles binds zinc and forms retroviral-type zinc fingers. AB - The role of zinc in retroviral gag protein function has been addressed through the application of high-resolution nuclear magnetic resonance spectroscopy to samples of the nucleocapsid protein (NCP, p7) isolated directly from infectious HIV-1 particles. Unlike reports for the NCP from avian myeloblastosis virus (AMV) particles [Jentoft et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7094], we find that the HIV-1 NCP binds 2 equiv of zinc tightly and stoichiometrically. Two dimensional NMR spectroscopic studies reveal that zinc binding induces formation of folded domains that are conformationally similar to (if not identical with) structures observed previously for relevant retroviral-type (RT) zinc finger peptides [formerly called zinc fingerlike peptides; Summers et al. (1990) Biochemistry 29, 329]. This finding is consistent with the hypothesis that the inability of mutant proteins (with substituted Cys and His residues) to package viral RNA results from deficient zinc-binding capability, which may have significant consequences in the development of vaccines for the prevention of AIDS. PMID- 2261435 TI - Physical properties of glycosyl diacylglycerols. 1. Calorimetric studies of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols. AB - The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water. PMID- 2261436 TI - Physical properties of glycosyl diacylglycerols. 2. X-ray diffraction studies of a homologous series of 1,2-Di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols. AB - X-ray diffraction methods were used to characterize the thermotropic polymorphism exhibited by aqueous dispersions of a homologous series of 1,2-O-acyl-3-O-(alpha D-glucopyranosyl)-sn-glycerols. Upon cooling from temperatures at which the acyl chains of these lipids are melted, all of these compounds form structures that exhibit both low-angle and wide-angle diffraction patterns consistent with the formation of lamellar L beta gel phases. After a suitable protocol of low temperature annealing, complex diffraction patterns consistent with the formation of highly ordered, lamellar, crystal-like phases are obtained. These patterns are similar for all of the compounds studied, suggesting that the unit cell structure is invariant. The assumption that the unit cell structure is invariant permits the assignment of phases to the diffraction orders, thereby making possible the construction of electron density profiles. These electron density profiles indicate that the crystal-like phases of these lipids are poorly hydrated structures with the hydrocarbon chains inclined at 35 degrees to the bilayer normal. The diffraction patterns of the crystal-like phases of these lipids changed abruptly at the calorimetrically determined phase transition temperatures to those characteristic of either lamellar liquid crystalline phases (N less than or equal to 17) or inverted nonbilayer phases. With these X-ray diffraction data we demonstrate that, at elevated temperatures, the shorter chain homologues (N less than or equal to 16) form cubic phases of the Pn3m space group, whereas the longer chain compounds form inverted hexagonal phases. PMID- 2261437 TI - Solution structures of human transforming growth factor alpha derived from 1H NMR data. AB - The 600-MHz 1H NMR spectrum of the des-Val-Val mutant of human transforming growth factor alpha (TGF-alpha) was reassigned at pH = 6.3. The conformation space of des-Val-Val TGF-alpha was explored by distance geometry embedding followed by restrained molecular dynamics refinement using NOE distance constraints and some torsion angle constraints derived from J-couplings. Over 80 long-range NOE constraints were found by completely assigning all resolved cross peaks in the NOESY spectra. Low NOE constraint violations were observed in structures obtained with the following three different refinement procedures: interactive annealing in DSPACE, AMBER 3.0 restrained molecular dynamics, and dynamic simulated annealing in XPLOR. The segment from Phe15 to Asp47 was found to be conformationally well-defined. Back-calculations of NOESY spectra were used to evaluate the quality of the structures. Our calculated structures resemble the ribbon diagram presentations that were recently reported by other groups. Several side-chain conformations appear to be well-defined as does the relative orientation of the C loop to the N-terminal half of the protein. PMID- 2261438 TI - Solution conformation of thymosin beta 4: a nuclear magnetic resonance and simulated annealing study. AB - The conformation of the polypeptide thymosin beta 4 in solutions of 60% (v/v) trifluoroethanol-d3 and 50% (v/v) hexafluoroisopropyl-d2 alcohol in water is investigated by nuclear magnetic resonance (NMR) spectroscopy. Under these conditions thymosin beta 4 adopts an ordered structure. By use of a combination of two-dimensional NMR techniques, the 1H NMR spectrum of thymosin beta 4 is assigned. A set of 180 approximate interproton distance constraints is derived from nuclear Overhauser enhancement (NOE) measurements. These, together with 33 phi constraints obtained for JNH alpha coupling data and the 23 psi dihedral angles identified on the basis of the pattern of short-range NOEs, form the basis of a three-dimensional structure determination by dynamical simulated annealing. The calculations are carried out starting from three initial structures, an alpha helix, an extended beta-strand, and a mixed alpha/beta structure. Ten independent structures are computed from each starting structure by using different random number seeds for the assignments of the initial velocities. All 30 calculated structures satisfy the experimental constraints, display very small deviations from idealized covalent geometry, and possess good nonbonded contacts. Analysis of the 30 converged structures indicates that there are two helical regions extending from residues 4-16 and from residues 30-40, which are well defined both in terms of atomic root mean square differences and backbone torsion angles. For the two helical regions individually the average backbone rms difference between all pairs of structures is approximately 2 A. The two helices exhibit typical amino acid preferences for specific locations at the ends of helices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261439 TI - Two different zinc sites in bovine 5-aminolevulinate dehydratase distinguished by extended X-ray absorption fine structure. AB - The zinc coordination in 5-aminolevulinate dehydratase was investigated by extended X-ray absorption fine structure (EXAFS) associated with the zinc K-edge. The enzyme binds 8 mol of zinc/mol of octameric protein, but only four zinc ions seem sufficient for full activity. We have undertaken a study on four forms of the enzyme: (a) the eight-zinc native enzyme; (b) the enzyme with only the four zinc sites necessary for full activation occupied; (c) the enzyme with the vacant sites of (b) occupied by four lead ions; (d) the product complex between (b) and porphobilinogen. We have shown that two structurally distinct types of zinc sites are available in the enzyme. The site necessary for activity has an average zinc environment best described by two/three histidines and one/zero oxygen from a group such as tyrosine or a solvent molecule at 2.06 +/- 0.02 A, one tyrosine or aspartate at 1.91 +/- 0.03 A, and one cysteine sulfur at 2.32 +/- 0.03 A with a total coordination of five ligands. The unoccupied site in (b), obtained by taking the difference spectrum between the spectra from samples (a) and (b), is dominated by a single contribution of four cysteinyl sulfur atoms at 2.28 +/- 0.02 A. Spectra from samples (c) and (d) show only small changes from that of (b), reflecting a slight rearrangement of the ligands around the zinc atom. PMID- 2261440 TI - Conformational preferences of synthetic peptides derived from the immunodominant site of the circumsporozoite protein of Plasmodium falciparum by 1H NMR. AB - Proton nuclear magnetic resonance and ultraviolet circular dichroism spectroscopy have been used to probe the conformational ensemble of the tandemly repeating tetrapeptide unit of the circumsporozoite coat protein of the malaria parasite Plasmodium falciparum. Peptides based on the Asn-Ala-Asn-Pro and Asn-Pro-Asn-Ala cadences and composed of one to three tetrapeptide units were synthesized and examined using one- and two-dimensional NMR spectroscopy. The chemical shift of the amide protons, the temperature dependence of the amide proton chemical shift, and the patterns of NOE connectivities in the various peptides give evidence for the presence of a substantial population of folded conformers in several of the peptides in water solution at pH 5.0. Correlations between the behavior of the tandemly repeated units in different peptides have been used to infer the structure(s) of the folded conformers. The data are consistent with the presence of turnlike structures stabilized by hydrogen bonding of the backbone amide protons of the alanines and the asparagine residues preceding them. Specific differences in the strengths of NOEs between peptides of different lengths indicate that the folded structure is considerably stabilized by the presence of the asparagine residue following the alanine. Differences between peptides with different cadences of the tandemly repeating unit indicate that a repeating structural motif is formed by the Asn-Pro-Asn-Ala-(Asn) cadence. PMID- 2261441 TI - Peptide-induced parallel DNA duplexes for oligopyrimidines. Stereospecificity in complexation for oligo(L-lysine) and oligo(L-ornithine). AB - It is shown that the cationic oligopeptides octadeca(L-lysine) (Lys18) and octadeca(L-ornithine) (Orn18) can induce a parallel duplex for the natural DNA oligomer dT10 with thymine-thymine base pairs. Complexation of the ammonium groups in the peptide side chains with the DNA phosphates leads to diminished electrostatic phosphate-phosphate repulsions, which allows this T-T base pair formation. From combined NOESY 1H NMR and molecular mechanics studies, it follows that the parallel duplex is right-handed, with the peptide located in the groove of the duplex. For the natural DNA oligomers dC10, d(C6T6), and d(T6C2T2), only Lys18 is able to induce the formation of parallel duplexes with C-C and T-T base pairs. It is shown that, for Orn18, a complexation must occur with one of the nonbonded oxygen atoms in the phosphate groups (OR) in such a way that unfavorable steric interactions are present with the C-C base pairs, which have a larger propellor twist angle than T-T base pairs. An analogy is presented between peptide complexation with the phosphates and the neutralization of the phosphate groups by methylation, which is known to lead to parallel duplexes with T-T base pairs (for both the Sp and Rp configurations) and C-C base pairs (only for the Sp configuration). PMID- 2261442 TI - Modification of DNA bases in mammalian chromatin by radiation-generated free radicals. AB - Modification of DNA bases in mammalian chromatin in aqueous suspension by ionizing radiation generated free radicals was investigated. Argon, air, N2O, and N2O/O2 were used for saturation of the aqueous system in order to provide different radical environments. Radiation doses ranging from 20 to 200 Gy (J.kg 1) were used. Thirteen products resulting from radical interactions with pyrimidines and purines in chromatin were identified and quantitated by using the technique of gas chromatography/mass spectrometry with selected-ion monitoring after acidic hydrolysis and trimethylsilylation of chromatin. The methodology used permitted analysis of the modified bases directly in chromatin without the necessity of isolation of DNA from chromatin first. The results indicate that the radical environment provided by the presence of different gases in the system had a substantial effect on the types of products and their quantities. Some products were produced only in the presence of oxygen, whereas other products were detected only in the absence of oxygen. Products produced under all four gaseous conditions were also observed. Generally, the presence of oxygen in the system increased the yields of the products with the exception of formamidopyrimidines. Superoxide radical formed in the presence of air, and to a lesser extent in the presence of N2O/O2, had no effect on product formation. The presence of oxygen dramatically increased the yields of 8-hydroxypurines, whereas the yields of formamidopyrimidines were not affected by oxygen, although these products result from respective oxidation and reduction of the same hydroxyl-adduct radicals of purines. The yields of the products were much lower than those observed previously with DNA. PMID- 2261443 TI - Use of Mono Q high-resolution ion-exchange chromatography to obtain highly pure and active Escherichia coli RNA polymerase. AB - A method for the purification of highly pure and active Escherichia coli RNA polymerase holoenzyme is described. This method is simple, reproducible, and can be performed at room temperature. The procedure involves the high-performance liquid chromatography of a partially purified RNA polymerase sample on a Mono Q ion-exchange column. Under the conditions used, RNA polymerase holoenzyme is well separated from the core RNA polymerase and other impurities. The purified RNA polymerase contains virtually no impurities as judged by SDS-polyacrylamide gel electrophoresis. The purified RNA polymerase holoenzyme contains the sigma 70 subunit in stoichiometric amounts and is at least 90% active. PMID- 2261444 TI - Interaction of porphyrin-containing macrotetracyclic receptor molecule with single-stranded and double-stranded polynucleotides. A photophysical study. AB - Photophysical methods have been used to study the interaction with nucleic acids of a macrotetracyclic cryptand molecule, Pbiph, containing a porphyrin groups, two macrocycles, and a biphenyl bridge. Pbiph binds with a higher affinity to single-stranded polynucleotides than to double-stranded ones. This selectivity, observed by binding and competition studies, using absorption and fluorescence spectroscopy, is pH dependent. Pbiph does not intercalate into double helices and is suggested to bind into the major groove. These features, selective single strand binding and nonintercalation, are attributed to steric effects of the bulky Pbiph molecule, resulting from the macropolyclic cryptand cage structure. PMID- 2261445 TI - Purification of a strand exchange stimulatory factor from Saccharomyces cerevisiae. AB - The SEP1 strand exchange protein of Saccharomyces cerevisiae catalyzes the formation of heteroduplex DNA joints between single-strand circles and homologous linear duplexes in vitro. Previous work [Kolodner, R., Evans, D. H., & Morrison, P. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5560-5564] showed that the optimal stoichiometry of SEP1 in this reaction was 1 SEP1 monomer per 12-14 nucleotides of single-stranded DNA. The work presented here describes the purification and characterization of a 33,000-dalton yeast protein that permits SEP1 to catalyze joint molecule formation at much lower stoichiometries. In the presence of this second factor, which has been designated SF1 for stimulatory factor 1, the optimal amount of SEP1 dropped to 1 SEP1 monomer per 725 nucleotides of single stranded DNA. At this concentration of SEP1, the rate of joint molecule formation increased approximately 3-fold over that seen in the unstimulated reaction (no SF1). Titration experiments indicated that when the concentration of SEP1 was reduced over 300-fold to 1 SEP1 molecule per 5800 nucleotides of single-stranded DNA, the stimulated reaction had the same rate and extent of joint molecule formation as the unstimulated reaction. The optimal amount of SF1 was 1 molecule of SF1 per 20 nucleotides of single-stranded DNA. Electron microscopic analysis showed that a bona fide strand exchange reaction produced the joint molecules in the stimulated reaction. The stimulated reaction had requirements that were essentially identical with those seen in the unstimulated reaction, including a lack of dependence on ATP. SF1 aggregated single-stranded and double-stranded DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261446 TI - Interaction of a Saccharomyces cerevisiae strand exchange stimulatory factor with DNA. AB - In the preceding paper (Norris & Kolodner, 1990), we described the purification of a Mr 33,000 polypeptide which dramatically stimulated the activity of SEP1, the yeast mitotic strand exchange protein. In this paper, we characterized this new protein, which was designated SF1, in the absence of SEP1. SF1 had a sedimentation coefficient of 1.7 S and a Stokes radius of 30 A, which was consistent with a calculated native molecular weight of 31,000, indicating that SF1 existed in solution as a monomer. Filter binding assays showed that SF1 bound preferentially to single-stranded rather than double-stranded DNA. Fluorescence spectroscopy analysis indicated that SF1 occluded approximately eight nucleotides when bound to single-stranded DNA and exhibited a dissociation constant, KD, of 2.83 x 10(-6) M. The binding of SF1 to single-stranded DNA was noncooperative and appeared to involve at least one tyrosine residue. SF1, in the absence of SEP1, stimulated the renaturation of homologous single-stranded DNA, suggesting that it might act directly in some phase of the strand exchange reaction. PMID- 2261447 TI - Phospholipid interactions of synthetic peptides representing the N-terminus of HIV gp41. AB - Peptides representing the N-terminal 23 residues of the surface protein gp41 of LAV1a and LAVmal strains of the human immunodeficiency virus were synthesized and their interactions with phospholipid vesicles studied. The peptides are surface active and penetrate lipid monolayers composed of negatively charged but not neutral lipids. Similarly, the peptides induce lipid mixing and solute (6 carboxyfluorescein) leakage of negatively charged, but not neutral, vesicles. Circular dichroism and infrared spectroscopy show that at low peptide:lipid ratios (approximately 1:200), the peptides bind to negatively charged vesicles as alpha-helices. At higher peptide:lipid ratios (1:30), a beta conformation is observed for the LAV1a peptide, accompanied by a large increase in light scattering. The LAVmal peptide showed less beta-structure and induced less light scattering. With neutral vesicles, only the beta conformation and a peptide:lipid ratio-dependent increase in vesicle suspension light scattering were observed for both peptides. We hypothesize that the inserted alpha-helical form causes vesicle membrane disruption whereas the surface-bound beta form induces aggregation. PMID- 2261448 TI - Phase separation in short-chain lecithin/gel-state long-chain lecithin aggregates. AB - Small bilayer particles form spontaneously from gel-state long-chain phospholipids such as dipalmitoylphosphatidylcholine and 0.2 mol fraction short chain lecithins (e.g., diheptanoyl-phosphatidylcholine). When the particles are incubated at temperatures greater than the Tm of the long-chain phosphatidylcholine (PC), the particles rapidly fuse (from 90-A to greater than or equal to 5000-A radius); this transition is reversible. A possible explanation for this behavior involves patching or phase separation of the short-chain component within the gel-state particle and randomization of both lipid species above Tm. Differential scanning calorimetry, 1H T1 values of proteodiheptanoyl-PC in diheptanoyl-PC-d26/dipalmitoyl-PC-d62 matrices of varying deuterium content, solid-state 2H NMR spectroscopy as a function of temperature, and fluorescence pyrene excimer-to-monomer ratios as a function of mole fraction diheptanoyl-PC provide evidence that such phase separation must occur. These results are used to construct a phase diagram for the diheptanoyl-PC/dipalmitoyl-PC system, to propose detailed geometric models for the different lipid particles involved, and to understand phospholipase kinetics toward the different aggregates. PMID- 2261449 TI - Microimmiscibility and three-dimensional dynamic structures of phosphatidylcholine-cholesterol membranes: translational diffusion of a copper complex in the membrane. AB - Saturated and unsaturated phosphatidylcholine (PC)-cholesterol membranes have been studied, with a special attention paid to fluid-phase immiscibility in cis unsaturated phosphatidylcholine (PC)-cholesterol membranes as previously proposed and to the three-dimensional structure of the membrane. The investigation was carried out with dual probes: a membrane-soluble, square-planar copper complex, (3-ethoxy-2-oxobutyraldehyde bis(N4,N4-dimethylthiosemicarbazonato]copper(II) (CuKTSM2), and one of several nitroxide radical lipid-type spin-labels. Bimolecular collision rates between metal ion and spin-label were determined by measuring the nitroxide spin-lattice relaxation times (T1's) in the presence and absence of CuKTSM2 by use of saturation-recovery ESR techniques, and from these measured rates, translational diffusion coefficients of CuKTSM2 were estimated. Profiles of the collision rate across the membrane bilayer were obtained with Tempocholine phosphatidic acid ester, 5-doxylstearic acid, 16-doxylstearic acid, and cholesterol-type spin-labels as a function of cholesterol mole fraction, length and unsaturation of acyl chains, and temperature. In the liquid crystalline phase of saturated PC membranes, incorporation of cholesterol decreases the collision rate at all depths in the membrane, and the effect of cholesterol is smallest in the middle of the bilayer. In trans-unsaturated PC membranes, a cholesterol-induced decrease of the collision rate was also observed, except in the head-group regions. In cis-unsaturated PC membranes, virtually no effect of cholesterol was observed on the collision rate, either with phospholipid-type spin-labels or with cholesterol-type spin-labels. This result is in clear contrast with our previous observation, in which the effect of cholesterol in cis-unsaturated PC membranes is small on the alkyl-chain motion of phospholipid-type spin-labels but large on the wobbling rotational diffusion of cholesterol-type spin-labels [Pasenkiewicz-Gierula, M., Subczynski, W. K., & Kusumi, A. (1990) Biochemistry 29, 4059-4069]. A model is proposed to explain these results in which the fluid-phase immiscibility is prevalent in cis unsaturated PC-cholesterol membranes, but where cholesterol-rich (cholesterol oligomeric) domains are small (several lipids) and/or of short lifetime (10(-9) s to less than 10(-7) s). It is suggested that this microimmiscibility arises from the structural nonconformability between the rigid cholesterol ring structure and the rigid bend at the cis double bonds in PC alkyl chains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2261450 TI - Subgel phases of n-saturated diacylphosphatidylcholines: a Fourier-transform infrared spectroscopic study. AB - The subgel phases of a homologous series of saturated straight-chain diacylphosphatidylcholines with hydrocarbon chains consisting of 10-18 carbon atoms were studied by Fourier-transform infrared spectroscopy. All of these lipids initially form a subgel phase which is spectroscopically similar to that obtained when fully hydrated multilamellar dispersions of dipalmitoylphosphatidylcholine are incubated at 0-4 degrees C for 2-4 days. However, further low-temperature incubation of those phosphatidylcholines with acyl chains of 16 or fewer carbon atoms results in the sequential formation of 1 or more additional, spectroscopically distinct subgel phases, with the number of such phases increasing as hydrocarbon chain length decreases. Our data indicate that the formation of all of these subgel phases involves both reorientation of the acyl chains and major changes in hydration and/or hydrogen-bonding interactions at the polar/apolar interfacial region of the lipid bilayer. We suggest that the driving force behind the formation of these Lc phases is the formation of an extended hydrogen-bonding network in the interfacial region of the bilayer and that the optimization of this network probably requires some distortion of the optimal packing of the acyl chains. As a result, an increase in acyl chain length makes the formation of these Lc phases less favorable and eventually prevents optimization of the hydrogen-bonding network at the bilayer polar/apolar interface. PMID- 2261451 TI - Fidelity in the aminoacylation of tRNA(Val) with hydroxy analogues of valine, leucine, and isoleucine by valyl-tRNA synthetases from Saccharomyces cerevisiae and Escherichia coli. AB - Several analogues of valine, leucine, and isoleucine carrying hydroxyl groups in the gamma- or delta-position have been tested in the aminoacylation of tRNA by valyl-tRNA synthetases from Saccharomyces cerevisiae and Escherichia coli. Results of the ATP/PPi exchange and of the aminoacylation reactions indicate that the amino acid analogues not only can form the aminoacyl adenylate intermediate but are also transferred to tRNA. However, the fact that the reaction consumes an excess of ATP indicates that the misactivated amino acid analogue is hydrolytically removed. Thus, valyl-tRNA synthetase from S. cerevisiae shows a high fidelity in forming valyl-tRNA. Although the much bulkier amino acid analogues allo- and iso-gamma-hydroxyvaline and allo- and iso-gamma hydroxyisoleucine are initially charged to tRNA, the misaminoacylated tRNA(Val) is enzymatically deacylated. This cleavage reaction is mediated by the hydroxyl groups of the amino acid analogues which are converted into the corresponding lactones. PMID- 2261452 TI - Transformation of glucocorticoid receptors bound to the antagonist RU 486: effects of alkaline phosphatase. AB - RU 486 is a synthetic steroid that binds avidly to glucocorticoid receptors without promoting their transformation into activated transcription factors. A significant part of this behavior has been shown to be due to a failure of the RU 486 bound receptor to be efficiently released from a larger (sedimenting at 8-9 S) multimeric complex containing the 90-kDa heat shock protein. Our studies have found that in vitro at 15 degrees C the RU 486-receptor was slowly released from the 8-9S complex and converted into a DNA binding protein by a process that could be blocked by sodium fluoride. Moreover, this transition was significantly accelerated by treatment with alkaline phosphatase. High-resolution anion exchange chromatography showed that the profile of receptor subspecies released from the 8-9S complex (in the absence of phosphatase treatment) was different for the RU 486 bound receptor when compared to the receptor occupied by the agonist triamcinolone acetonide. Production of the earliest eluting receptor form (peak A) was inhibited with RU 486. Peak A had previously been shown to be the predominant form of the receptor possessing a capacity to bind DNA. Treatment of the RU 486-receptor with alkaline phosphatase increased the formation of the peak A subspecies as well as the capacity of receptor to bind DNA-cellulose. Taken together, the results indicate that phosphorylation of the receptor or a tightly bound factor contributes to defining the capacity with which individual steroids can promote dissociation of the 8-9S complex and conversion of the glucocorticoid receptor into a DNA-binding protein. PMID- 2261453 TI - Prothrombin activation on membranes with anionic lipids containing phosphate, sulfate, and/or carboxyl groups. AB - Factor Xa catalyzed prothrombin activation is strongly stimulated by the presence of negatively charged membranes plus calcium ions. Here we report experiments in which we determined the prothrombin-converting activity of phosphatidylcholine (PC) membranes that contain varying amounts of different anionic lipids, viz., phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylmethanol (MePA), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidyl-beta lactate (PLac), sulfatides (SF), sodium dodecyl sulfate (SDS), and oleic acid. All anionic lipids tested were able to accelerate factor Xa catalyzed prothrombin activation, in both the absence and presence of the protein cofactor Va. This shows that the prothrombin-converting activity of negatively charged membranes is not strictly dependent on the presence of a phosphate group but that lipids which contain a carboxyl or sulfate moiety are also able to promote the formation of a functionally active prothrombinase complex. In the absence of factor Va, the prothrombin-converting activity of membranes with MePA, PG, PE, PLac, SF, or SDS was strongly inhibited at high ionic strength, while the activity of PS- and PA containing membranes was hardly affected by ionic strength variation. This suggests that in the case of the ionic strength sensitive lipids electrostatic forces play an important role in the formation of the membrane-bound prothrombinase complex. For PS and to a lesser extent for PA we propose that the formation of a coordinated complex (chelate complex) with Ca2+ as central ion and ligands provided by the gamma-carboxyglutamic acid residues of prothrombin and factor Xa and the polar head group of phospholipids is the major driving force in protein-membrane association. Our data indicate that the anionic lipids used in this study can be useful tools for further investigation of the molecular interactions that play a role in the assembly of a membrane-bound prothrombinase complex. Membranes that were solely composed of PC can also considerably enhance prothrombin activation in the presence of factor Va. This activity of PC is only observed on membranes which are composed of PC that contains unsaturated hydrocarbon side chains. Membranes prepared from phosphocholine-containing lipids with saturated hydrocarbon side chains such as dimyristoyl-PC, dipalmitoyl-PC, distearoyl-PC, and dioctadecylglycerophosphocholine hardly accelerated prothrombin activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261454 TI - Characterization of vanadium bromoperoxidase from Macrocystis and Fucus: reactivity of vanadium bromoperoxidase toward acyl and alkyl peroxides and bromination of amines. AB - Vanadium bromoperoxidase (V-BrPO) has been isolated and purified from the marine brown algae Fucus distichus and Macrocystis pyrifera. V-BrPO catalyzes the oxidation of bromide by hydrogen peroxide, resulting in the bromination of certain organic acceptors or the formation of dioxygen. V-BrPO from F. distichus and M. pyrifera have subunit molecular weights of 65,000 and 74,000, respectively, and specific activities of 1580 units/mg (pH 6.5) and 1730 units/mg (pH 6) for the bromination of monochlorodimedone, respectively. As isolated, the enzymes contain a substoichiometric vanadium/subunit ratio; the vanadium content and specific activity are increased by addition of vanadate. V-BrPO (F. distichus, M. pyrifera, and Ascophyllum nodosum) also catalyzes the oxidation of bromide using peracetic acid. In the absence of an organic acceptor, a mixture of oxidized bromine species (e.g., hypobromous acid, bromine, and tribromide) is formed. Bromamine derivatives are formed from the corresponding amines, while 5 bromocytosine is formed from cytosine. In all cases, the rate of the V-BrPO catalyzed reaction is much faster than that of the uncatalyzed oxidation of bromide by peracetic acid, at pH 8.5, 1 mM bromide, and 2 mM peracetic acid. In contrast to hydrogen peroxide, V-BrPO does not catalyze formation of dioxygen from peracetic acid in either the presence or absence of bromide. V-BrPO also uses phenylperacetic acid, m-chloroperoxybenzoic acid, and p-nitroperoxybenzoic acid to catalyze the oxidation of bromide; dioxygen is not formed with these peracids. V-BrPO does not catalyze bromide oxidation or dioxygen formation with the alkyl peroxides ethyl hydroperoxide, tert-butyl hydroperoxide, and cuminyl hydroperoxide. PMID- 2261455 TI - Photocleavage of myosin subfragment 1 by vanadate. AB - The heavy chain of myosin's subfragment 1 (S1) was cleaved at two distinct sites (termed V1 and V2) after irradiation with UV light in the presence of millimolar concentrations of vanadate and in the absence of nucleotides or divalent metals. The V1 site cleavage appeared to be identical with the previously described active site cleavage at serine-180, which is effected by irradiation of a photomodified form of the S1-MgADP-Vi complex [Cremo, C. R., Grammer, J. C., & Yount, R. G. (1989) J. Biol. Chem. 264, 6608-6011]. The V2 site was cleaved specifically, without cleavage at the V1 site, first by formation of the light stable S1-Co2+ADP-Vi complex at the active site [Grammer, J. C., Cremo, C. R., & Yount, R. G. (1988) Biochemistry 27, 8408-8415] and then by irradiation in the presence of millimolar vanadate. By gel electrophoresis, the V2 site was localized to a region about 20 kDa from the COOH terminus of the S1 heavy chain. From the results of tryptic digestion experiments, the COOH-terminal V2 cleavage peptide appeared to contain lysine-636 in the linker region between the 50- and 20-kDa tryptic peptides of the heavy chain. This site appeared to be the same site cleaved by irradiation of S1 (not complexed with Co2+ADP-Vi) in the presence of millimolar vanadate as previously described [Mocz, G. (1989) Eur. J. Biochem. 179, 373-378]. Cleavage at the V2 site was inhibited by Co2+ but was not significantly affected by the presence of nucleotides or Mg2+ ions. Tris buffer significantly inhibited V2 cleavage. From the results of UV-visible absorption, 51V NMR, and frozen-solution EPR spectral experiments, it was concluded that irradiation with UV light reduced vanadate +5 to the +4 oxidation state, which was then protected from rapid reoxidation by O2 by complexation with the Tris buffer. The relatively stable reduced form or forms of vanadium were not competent to cleave S1 at either the V1 or the V2 site. 51V NMR titration experiments indicated that a tetrameric species of vanadium preferentially bound to S1 and to the S1-MgADP-Vi complex, whereas no binding of either the monomeric or dimeric species could be detected. These results suggest that the vanadate tetramer was responsible for the photocleavage of S1 which occurred at both the V1 and V2 sites in the absence of nucleotides or divalent metals. PMID- 2261457 TI - An inverse face-centered cubic phase formed by diacylglycerol-phosphatidylcholine mixtures. AB - Fully hydrated unsaturated diacylglycerol-phosphatidylcholine mixtures are found to adopt an inverse face-centered cubic phase, of crystallographic cubic aspect 15. The same behavior is observed for either the 1,2- or 1,3-isomer of the diacylglycerol. This Q15 cubic phase, of probable space group Fd3m (Q227), occurs between an inverse hexagonal (HII) phase and an inverse micellar (L2) solution, with increasing diacylglycerol concentration, which implies that the mean curvature of the interface is more negative than that of the HII phase. This behavior is quite different from that of the more usual bicontinuous inverse cubic phases Pn3m (Q224), Im3m (Q229), and Ia3d (Q230), which normally occur between the lamellar L alpha and the HII phases. One possible structure for the Fd3m cubic phase has recently been proposed (Mariani, P., Luzzati, V., & Delacroix, H. (1988) J. Mol. Biol. 204, 165-189), consisting of tetrahedrally arranged clusters of inverse micelles surrounded by a continuous cage of tetrahedrally connected water/lipid (inverse) channels. PMID- 2261456 TI - Interactions at the nucleic acid binding site of the avian retroviral nucleocapsid protein: studies utilizing the fluorescent probe 4,4' bis(phenylamino)(1,1'-binaphthalene)-5,5'-disulfonic acid. AB - The structural and functional properties of the nucleocapsid (NC) protein of the avian myeloblastosis virus were examined by steady-state fluorescence and fluorescence anisotropy measurements of the complex between the NC and the extrinsic fluorophore 4,4'-bis(phenylamino)(1,1'-binaphthalene)-5,5'-disulfonic acid (bis-ANS). The intrinsic fluorescence of bis-ANS is enhanced many fold upon forming a complex with the NC. Between 2 and 10 molecules of bis-ANS bind strongly to the NC, with an overall Kd of less than 10(-6) M. The emission of bis ANS in the complex can also be induced by excitation at 298 nm, indicating that energy is transferred from Trp 80, the sole tryptophan in the NC protein, to bis ANS. The energy transferred between the Trp 80 and bis-ANS was analyzed to yield a calculated distance of separation between these fluorophores of 28 +/- 3 A; thus, Trp 80 is well removed from the nearest bound bis-ANS. The fluorescence emission of bis-ANS in the NC.bis-ANS complex is efficiently quenched by added salts and by poly(A), suggesting that salt (presumably anions), nucleic acid, and bis-ANS bind to the same, positively charged region on the NC protein. A site size of six nucleotides was determined for nucleic acid binding to the NC protein, with an estimated Kd of less than 10(-6) M. Salt (anion) binding is strong, but nonspecific, with a Kapp of 4 mM, raising the possibility that anion binding to the NC protein might regulate the interaction of the NC with viral RNA inside the host cell. PMID- 2261458 TI - Self-cleavage of hepatitis delta virus genomic strand RNA is enhanced under partially denaturing conditions. AB - Self-cleavage of a polyribonucleotide containing an autocleaving sequence from the genomic strand of hepatitis delta virus was enhanced by conditions that destabilized RNA structure. Self-cleavage of the transcripts used in this study required Mg2+ (or another divalent cation), and in the absence of denaturants, maximum cleavage was observed at very low Mg2+ concentrations (0.05-0.1 mM). However, at 37 degrees C and in the presence of 2-10 mM Mg2+ the rate of cleavage was increased as much as 50-fold with the addition of urea to 5 M or formamide to 10 M. Cleavage was prevented by higher concentrations of the same reagents (9.5 M urea or 22.5 M formamide), presumably because a structure required for self cleavage is disrupted by strongly denaturing conditions. In contrast to a previous report [Wu, H.-N., & Lai, M. M. C. (1989) Science 243, 652-654], we find that chelating Mg2+ with EDTA terminates the cleavage reaction without promoting measurable amounts of ligation of the cleavage products. The ability of denaturants to promote rapid self-cleavage in vitro raises the possibility that an unidentified factor could have a similar effect in vivo. PMID- 2261459 TI - Thermal unfolding studies of a leucine zipper domain and its specific DNA complex: implications for scissor's grip recognition. AB - A newly recognized class of eukaryotic transcription factors is characterized by a bipartite sequence motif, consisting of a C-terminal dimerization region (the leucine zipper) and an N-terminal basic region (which mediates DNA binding). In studies of isolated leucine zipper peptides, the dimerization region has been characterized as a coiled coil of parallel alpha-helices. To extend these studies to a functional DNA-binding domain, we describe CD studies of the thermal unfolding and refolding of a 58-residue fragment of GCN4, the yeast homologue of the c-Jun protooncoprotein. This fragment, which contains the complete leucine zipper and basic region, retains the DNA-binding properties of the intact protein. The GCN4 DNA-binding domain exhibits two independent helix-coil unfolding transitions. The major transition (midpoint 65 degrees C) is due to dissociation of the dimer in accord with previous studies of an isolated leucine zipper. A novel pretransition in the temperature range 0-40 degrees C is also observed, which reflects partial stabilization of the nascent helix in the basic region. Remarkably, complete folding of the basic region as an alpha-helix requires specific DNA binding, and the protein-DNA complex exhibits a single cooperative unfolding transition. These results support a major feature of the recently proposed "scissor's grip" model of DNA recognition, in which the basic regions extend from the leucine zipper as bifurcating alpha-helical arms. PMID- 2261460 TI - A bifunctional fusion protein containing Fc-binding fragment B of staphylococcal protein A amino terminal to antidigoxin single-chain Fv. AB - A bifunctional molecule was genetically engineered which contained an amino terminal effector domain that bound immunoglobulin Fc (fragment B of staphylococcal protein A) and a carboxyl-terminal domain that bound digoxin [a single-chain Fv (sFv)]. Effector and sFv binding properties were virtually identical with those of the parent molecules, despite the proximity of the FB to the sFv combining site. This finding is unprecedented since in all molecules of the natural immunoglobulin superfamily, the antigen binding domain is amino terminal to the effector domain. The FB-sFv sequence was encoded in a single synthetic gene and expressed as a 33,106 molecular weight protein in Escherichia coli. After purification, renaturation, and affinity isolation, yield of active fusion protein were 110 mg/L of fermented cells (18.5-g cell paste). Bifunctionality was confirmed by the ability of FB-sFv to cross-link IgG to digoxin-bovine serum albumin, as measured by plate assays and by Ouchterlony analysis. Analysis of the expressed fusion protein suggests that the sFv holds promise for the development of multifunctional, targetable single-chain proteins. PMID- 2261461 TI - Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease. AB - To quantitate the contributions of the large hydrophobic residues in staphylococcal nuclease to the stability of its native state, single alanine and glycine substitutions were constructed by site-directed mutagenesis for each of the 11 leucine, 9 valine, 7 tyrosine, 5 isoleucine, 4 methionine, and 3 phenylalanine residues. In addition, each isoleucine was also mutated to valine. The resulting collection of 83 mutant nucleases was submitted to guanidine hydrochloride denaturation using intrinsic tryptophan fluorescence to monitor the equilibrium constant between the native and denatured states. From analysis of these data, each mutant protein's stability to reversible denaturation (delta GH2O) and sensitivity to guanidine hydrochloride (mGuHCl or d(delta G)/d[GuHCl]) were obtained. Four unexpected trends were observed. (1) A striking bipartite distribution was found for sites of mutations that altered mGuHCl: mutations that increased this parameter only involved residues that contribute side chains to the major hydrophobic core centered around a five-strand beta-barrel, whereas mutations that caused mGuHCl to decrease clustered around a second, smaller and less well-defined hydrophobic core. (2) The average stability loss for mutants in each of the six residue classes was 2-3 times greater than that estimated on the basis of the free energy of transfer of the hydrophobic side chain from water to n-octanol. (3) The magnitude of the stability loss on substituting Ala or Gly for a particular type of amino acid varied extensively among the different sites of its occurrence in nuclease, indicating that the environment surrounding a specific residue determines how large a stability contribution its side chain will make.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261462 TI - Photolysis and deacylation of inhibited chymotrypsin. AB - Inhibited chymotrypsin was reactivated through the photolysis of the covalently bound light-reversible cinnamates described in our previous paper [Stoddard, B.L., Bruhnke, J., Porter, N.A., Ringe, D., & Petsko, G. (1990) Biochemistry 29, 4871-4879]. The light-induced deacylation was accomplished both in solution and in protein crystals, with the release of inhibitor from the crystal monitored and confirmed by X-ray diffraction. The product of photolysis has been characterized as a 3-methylcoumarin, leading to a mechanism for light-driven deacylation of an internal lactonization that is dependent on the presence of an internal hydroxyl nucleophile. The acyl enzyme formed from cinnamate A is not suitable for photochemical studies, as the complex has a short half-life in solution and does not have a chromophore that is well separated from protein absorbance. Cinnamate B, with a p-diethylamino substituent, shows an enzyme deacylation rate enhancement of 10(9) for the cis photoisomer relative to the trans starting material. The half-life and deacylation rate of this compound in the E-I complex after photon absorption have been directly measured by subsecond UV absorption studies. X-ray diffraction studies of photoactivation using a flow cell show that the cinnamate B acyl enzyme complex is fully capable of light-induced isomerization and regeneration of native enzyme in the crystalline state. The E-I complex formed upon binding of cinnamate A, however, shows little if any effect from irradiation due to competitive absorbance by the highly concentrated protein at the shorter UV wavelengths. Photolysis of cinnamate B appears to occur on a time scale fast enough for applications in crystallographic studies of enzymatic intermediate-state structures. PMID- 2261463 TI - Use of site-directed mutagenesis to identify valine-573 in the S'1 binding site of rat neutral endopeptidase 24.11 (enkephalinase). AB - On the basis of the identity of a segment of the amino acid sequence within the active site of the bacterial enzyme thermolysin and the mammalian enzyme neutral endopeptidase 24.11, the possible involvement of valine-573 of neutral endopeptidase 24.11 in substrate binding was investigated. Valine-573 was changed to leucine and to alanine by site-directed mutagenesis. The effect of these mutations on inhibitor binding and substrate catalysis was examined with a series of compounds containing variable P'1 residues. With a small P'1 residue such as alanine, both mutant enzymes exhibited kinetic properties essentially the same as the wild-type enzyme. However, with larger P'1 residues such as phenylalanine, tyrosine, and leucine, the Val573Leu mutant showed a 24-100-fold decrease in inhibitor affinity. Similarly substrates containing bulky P'1 residues showed a 10-40-fold decrease in Vmax with little change in Km. In contrast, the Val573Ala mutant showed only modest changes in terms of inhibitor binding or substrate turnover. These results support the proposed role of valine-573 as a part of the hydrophobic binding pocket, S'1 binding subsite, of neutral endopeptidase 24.11. PMID- 2261464 TI - Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. AB - IgE-binding protein (epsilon BP) refers to a protein originally identified in rat basophilic leukemia cells by virtue of its affinity for IgE. It is now known to be a beta-galactoside-binding lectin equivalent to carbohydrate-binding protein 35 (CBP 35). More recently, its identity to Mac-2, a macrophage cell-surface protein, has been established. cDNA coding for human epsilon BP has been cloned from a human HeLa cell cDNA library and contains an open reading frame of 750 base pairs encoding a 250 amino acid protein. Like the rat and murine counterparts, the human epsilon BP amino acid sequence can be divided into two domains with the amino-terminal domain consisting of a highly conserved repetitive sequence (YPGXXXPGA) and the carboxyl-terminal domain containing sequences shared by other S-type lectins. The human epsilon BP sequence exhibits extensive homology to murine and rat epsilon BP with 84% and 82% identity, respectively. The homology is particularly striking in the carboxyl-terminal domain where 95% identity is found between human and murine sequences in a stretch of over 70 amino acids. A survey of epsilon BP mRNA expression from several lymphocyte cell lines revealed that the level of epsilon BP transcription may reflect a relationship between cell differentiation and epsilon BP expression. Finally, human epsilon BP was purified from several human cell lines and shown to possess lactose-binding characteristics and cross-species reactivity to murine IgE. Surprisingly, three different human myeloma IgE proteins did not show reactivity to human epsilon BP. However, after neuraminidase treatment of each human IgE, pronounced binding to epsilon BP was observed, thereby indicating that only specific IgE glycoforms can be recognized by epsilon BP. PMID- 2261465 TI - Structure, stability, and receptor interaction of cholera toxin as studied by Fourier-transform infrared spectroscopy. AB - The structure and thermal stability of isolated B and A subunits of cholera toxin, as well as the interaction of the B subunit with a ganglioside GM1 receptor, were studied by Fourier-transform infrared spectroscopy. The B subunit of the toxin is highly folded; its secondary structure consists predominantly of beta-sheets. The temperature dependence of the infrared spectrum indicates that the B subunit undergoes thermal unfolding in the temperature range between approximately 66 and 78 degrees C. Binding to the ganglioside GM1 receptor or to its oligosaccharide moiety results in only marginal, if any, change in the secondary structure of the B subunit; however, the receptor-associated subunit does show a markedly increased thermal stability. The secondary structure of the enzymatically active A subunit is less ordered and much less stable than that of the B subunit. The relatively loose folding of the A subunit is likely to be of importance for the effective membrane translocation of this subunit. PMID- 2261466 TI - 1H NMR assignment and secondary structure of the Ca2(+)-free form of the amino terminal epidermal growth factor like domain in coagulation factor X. AB - Blood coagulation factor X is composed of discrete domains, two of which are homologous to the epidermal growth factor (EGF). The N-terminal EGF like domain in factor X (fX-EGFN), residues 45-86 of the intact protein, contains a beta hydroxylated aspartic acid and has one Ca2(+)-binding site. Using 2D NMR techniques, we have made a full assignment of the 500-MHz 1H NMR spectrum of Ca2(+)-free fX-EGFN. On the basis of this assignment and complementary NOESY experiments, we have also determined the secondary structure of Ca2(+)-free fX EGFN in water solution. Residues 45-49 are comparatively mobile, whereas residues 50-56 are constrained by two disulfide bonds to one side of an antiparallel beta sheet involving residues 59-64 and 67-72. Another antiparallel beta-sheet involves residues 76-77 and 83-84. A small, parallel beta-sheet connects residues 80-81 and 55-56 and thereby orients the two antiparallel beta-sheets relative to each other. Four beta-turns are identified, involving residues 50-53, 56-59, 64 67, and 73-76. Residues 78-82 adopt an extended bend structure. On the basis of secondary structure and the location of the three disulfide bonds, we find that Asp 46, Asp 48, and Hya 63 are sufficiently close to each other to form a Ca2(+) binding site. However, the amino terminus of the Ca2(+)-free form of fX-EGFN is not part of a triple-stranded beta-sheet as in other EGF like peptides. Differences and similarities between fX-EFGN and murine EGF with respect to secondary structure and conformational shifts are discussed. PMID- 2261467 TI - Formation, crystal structure, and rearrangement of a cytochrome P-450cam iron phenyl complex. AB - Cytochrome P-450cam reacts with phenyldiazene (PhN = NH), or less efficiently with phenylhydrazine, to give a catalytically inactive complex with an absorption maximum at 474 nm. The prosthetic group extracted anaerobically from the inactivated protein has the spectroscopic properties of a sigma phenyl-iron complex and rearranges, on exposure to air and acid, to an approximately equal mixture of the four N-phenylprotoporphyrin IX regioisomers. The crystal structure of the intact protein complex, refined at 1.9-A resolution to an R factor of 20%, confirms that the phenyl group is directly bonded through one of its carbons to the iron atom. The phenyl ring is tilted from the heme normal by about 10 degrees in the opposite direction from that in which carbon monoxide tilts when bound to P-450cam. Camphor, the natural substrate for P-450cam, is larger than a phenyl group and hydrogen bonds to Tyr 96, the only hydrophilic residue near the active site. Electron density in the active site in addition to that contributed by the phenyl group suggests that two water molecules occupy part of the camphor binding site but are not within hydrogen-bonding distance of Tyr 96. As observed in a previous crystallographic study of inhibitor-P-450cam complexes [Poulos, T.L., & Howard, A.J. (1987) Biochemistry 26, 8165-8174], there are large changes in both the atomic positions and mobilities of the residues in the proposed substrate access channel region of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261468 TI - Intrinsic fluorescence of a truncated Bordetella pertussis adenylate cyclase expressed in Escherichia coli. AB - A truncated, 432 residue long, Bordetella pertussis adenylate cyclase expressed in Escherichia coli was analyzed for intrinsic fluorescence properties. The two tryptophans (Trp69 and Trp242) of adenylate cyclase, each situated in close proximity to residues important for catalysis or binding of calmodulin (CaM), produced overlapping fluorescence emission bands upon excitation at 295 nm. CaM, alone or in association with low concentrations of urea, induced important modifications in the spectra of adenylate cyclase such as shifts of the maxima and change in the shape of the bands. From these changes and from the fluorescence spectrum of a modified form of adenylate cyclase, in which a valine residue was substituted for Trp242, it was deduced that, upon binding of CaM to the wild-type adenylate cyclase, only the environment of Trp242 was affected. The fluorescence maximum of this residue, which is more exposed to the solvent than Trp69 in the absence of CaM, is shifted by 13 nm to shorter wavelength upon interaction of protein with its activator. Trypsin cleaved adenylate cyclase into two fragments, one carrying the catalytic domain, and the second carrying the CaM binding domain (Ladant et al., 1989). The isolated peptides conserved most of the environment around their single tryptophan residues, as in the intact adenylate cyclase, which suggests that the two domains of truncated B. pertussis adenylate cyclase also conserved most of their three-dimensional structure in the isolated forms. PMID- 2261469 TI - Solid-state NMR studies of the mechanism of the opsin shift in the visual pigment rhodopsin. AB - Solid-state 13C NMR spectra have been obtained of bovine rhodopsin and isorhodopsin regenerated with retinal selectively 13C labeled along the polyene chain. In rhodopsin, the chemical shifts for 13C-5, 13C-6, 13C-7, 13C-14, and 13C 15 correspond closely to the chemical shifts observed in the 11-cis protonated Schiff base (PSB) model compound. Differences in chemical shift relative to the 11-cis PSB chloride salt are observed for positions 8 through 13, with the largest deshielding (6.2 ppm) localized at position 13. The localized deshielding at C-13 supports previous models of the opsin shift in rhodopsin that place a protein perturbation in the vicinity of position 13. Spectra obtained of isorhodopsin regenerated with 13C-labeled 9-cis-retinals reveal large perturbations at 13C-7 and 13C-13. The similar deshielding of the 13C-13 resonance in both pigments supports the presence of a protein perturbation near position 13. However, the chemical shifts at positions 7 and 12 in isorhodopsin are not analogous to those observed in rhodopsin and suggest that the binding site interactions near these positions are different for the two pigments. The implications of these results for the mechanism of the opsin shift in these proteins are discussed. PMID- 2261470 TI - Effect of phosphorylation on hydrogen-bonding interactions of the active site histidine of the phosphocarrier protein HPr of the phosphoenolpyruvate-dependent phosphotransferase system determined by 15N NMR spectroscopy. AB - The phosphocarrier protein HPr of the phosphoenolpyruvate-dependent sugar transport system of Escherichia coli can exist in a phosphorylated and a nonphosphorylated form. During phosphorylation, the phosphoryl group is carried on a histidine residue, His15. The hydrogen-bonding state of this histidine was examined with 15N NMR. For this purpose we selectively enriched the histidine imidazole nitrogens with 15N by supplying an E. coli histidine auxotroph with the amino acid labeled either at the N delta 1 and N epsilon 2 positions or at only the N delta 1 position. 15N NMR spectra of two synthesized model compounds, phosphoimidazole and phosphomethylimidazole, were also recorded. We show that, prior to phosphorylation, the protonated His15 N epsilon 2 is strongly hydrogen bonded, most probably to a carboxylate moiety. The H-bond should strengthen the nucleophilic character of the deprotonated N delta 1, resulting in a good acceptor for the phosphoryl group. The hydrogen bond to the His15 N delta 1 breaks upon phosphorylation of the residue. Implications of the H-bond structure for the mechanism of phosphorylation of HPr are discussed. PMID- 2261471 TI - Assignment of the side-chain 1H and 13C resonances of interleukin-1 beta using double- and triple-resonance heteronuclear three-dimensional NMR spectroscopy. AB - The assignment of the aliphatic 1H and 13C resonances of IL-1 beta, a protein of 153 residues and molecular mass 17.4 kDa, is presented by use of a number of novel three-dimensional (3D) heteronuclear NMR experiments which rely on large heteronuclear one-bond J couplings to transfer magnetization and establish through-bond connectivities. These 3D NMR experiments circumvent problems traditionally associated with the application of conventional 2D 1H-1H correlation experiments to proteins of this size, in particular the extensive chemical shift overlap which precludes the interpretation of the spectra and the reduced sensitivity arising from 1H line widths that are often significantly larger than the 1H-1H J couplings. The assignment proceeds in two stages. In the first step the 13C alpha chemical shifts are correlated with the NH and 15N chemical shifts by a 3D triple-resonance NH-15N-13C alpha (HNCA) correlation experiment which reveals both intraresidue NH(i)-15N(i)-13C alpha (i) and some weaker interresidue NH(i)-15N(i)-C alpha (i-1) correlations, the former via intraresidue one-bond 1JNC alpha and the latter via interresidue two-bond 2JNC alpha couplings. As the NH, 15N, and C alpha H chemical shifts had previously been sequentially assigned by 3D 1H Hartmann-Hahn 15N-1H multiple quantum coherence (3D HOHAHA-HMQC) and 3D heteronuclear 1H nuclear Overhauser 15N-1H multiple quantum coherence (3D NOESY-HMQC) spectroscopy [Driscoll, P.C., Clore, G.M., Marion, D., Wingfield, P.T., & Gronenborn, A.M. (1990) Biochemistry 29, 3542-3556], the 3D triple-resonance HNCA correlation experiment permits the sequence-specific assignments of 13C alpha chemical shifts in a straightforward manner. The second step involves the identification of side-chain spin systems by 3D 1H-13C-13C-1H correlated (HCCH-COSY) and 3D 1H-13C-13C-1H total correlated (HCCH-TOCSY) spectroscopy, the latter making use of isotropic mixing of 13C magnetization to obtain relayed connectivities along the side chains. Extensive cross-checks are provided in the assignment procedure by examination of the connectivities between 1H resonances at all the corresponding 13C shifts of the directly bonded 13C nuclei. In this manner, we were able to obtain complete 1H and 13C side-chain assignments for all residues, with the exception of 4 (out of a total of 15) lysine residues for which partial assignments were obtained. The 3D heteronuclear correlation experiments described are highly sensitive, and the required set of three 3D spectra was recorded in only 1 week of measurement time on a single uniformly 15N/13C-labeled 1.7 mM sample of interleukin-1 beta.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2261472 TI - Study of the binding of single-stranded DNA-binding protein to DNA and poly(rA) using electric field induced birefringence and circular dichroism spectroscopy. AB - Binding of the single-stranded DNA-binding protein (SSB) of Escherichia coli to single-stranded (ss) polynucleotides produces characteristic changes in the absorbance (OD) and circular dichroism (CD) spectra of the polynucleotides. By use of these techniques, complexes of SSB protein and poly(rA) were shown to display two of the binding modes reported by Lohman and Overman [Lohman, T.M., & Overman, L. (1985) J. Biol. Chem. 260, 3594-3603]. The circular dichroism spectra of the "low salt" (10 mM NaCl) and "high salt" (greater than 50 mM NaCl) binding mode are similar in shape, but not in intensity. SSB binding to poly(rA) yields a complexed CD spectrum that shares several characteristics with the spectra obtained for the binding of AdDBP, GP32, and gene V protein to poly(rA). We therefore propose that the local structure of the SSB-poly(rA) complex is comparable to the structures proposed for the complexes of these three-stranded DNA-binding proteins with DNA (and RNA) and independent of the SSB-binding mode. Electric field induced birefringence experiments were used to show that the projected base-base distance of the complex is about 0.23 nm, in agreement with electron microscopy results. Nevertheless, the local distance between the successive bases in the complex will be quite large, due to the coiling of the DNA around the SSB tetramer, thus partly explaining the observed CD changes induced upon complexation with single-stranded DNA and RNA. PMID- 2261473 TI - Bradykinin and its Gly6 analogue are substrates of cyclophilin: a fluorine-19 magnetization transfer study. AB - Fluorine-19 magnetization transfer experiments have been used to determine the rates of cis/trans isomerization about the X-Pro7 peptide bond in [p-fluoro Phe8]bradykinin (cis/trans ratio approximately 0.1) and its Gly6 analogue (cis/trans ratio approximately 0.4). The measurements were carried out both prior to and after the addition of cyclophilin, which has recently been shown to have peptidyl-proline cis/trans isomerase activity and is the apparent target enzyme of the immunosuppressive agent cyclosporin A. Magnetization transfer measurements over the temperature range 40-75 degrees C in the absence of enzyme give activation energies of 22.8 and 23.0 kcal/mol for [p-fluoro-Phe8]bradykinin and its Gly6 analogue, respectively. The values for the uncatalyzed cis----trans rate constant, kc, are determined by extrapolation to be 4.8 x 10(-2) and 2.1 x 10(-2) s-1 for the two peptides at 25 degrees C. The enzyme-catalyzed enhancement of the cis/trans interconversion rate was proportional to added cyclophilin concentration and was strongly sequence specific, with bradykinin a much better substrate than [Gly6]bradykinin. At a peptide concentration of 2.2 mM, the catalytic activity expressed as kc per micromolar cyclophilin was determined to be 1.2 s-1/microM for [p-fluoro-Phe8]bradykinin and 0.13 s-1/microM for the Gly6 analogue. The increased cis----trans interconversion rates were strongly inhibited by cyclosporin A and the 6-(methylalanine) derivative, which bind to cyclophilin, but not by the 1-(tetrahydrofurfuryl) derivative of cyclosporin that binds weakly. PMID- 2261474 TI - Binding of the antitumor drug nogalamycin and its derivatives to DNA: structural comparison. AB - The three-dimensional molecular structures of the complexes between a novel antitumor drug nogalamycin and its derivative U-58872 with a modified DNA hexamer d[m5CGT(pS)Am5CG] have been determined at 1.7- and 1.8-A resolution, respectively, by X-ray diffraction analyses. Both structures (in space group P6(1)) have been refined with constrained refinement procedure to final R factors of 0.208 (3386 reflections) and 0.196 (2143 reflections). In both complexes, two nogalamycins bind to the DNA hexamer double helix in a 2:1 ratio with the elongated aglycon chromophore intercalated between the CpG steps at both ends of the helix. The aglycon chromophore spans across the GC Watson-Crick base pairs with its nogalose lying in the minor groove and the aminoglucose lying in the major groove of the distorted B-DNA double helix. Most of the sugars remain in the C2'-endo pucker family, except three deoxycytidine residues (terminal C1, C7, and internal C5). All nucleotides are in the anti conformation. Specific hydrogen bonds are found in the complex between the drug and guanine-cytosine bases in both grooves of the helix. One hydroxyl group of the aminoglucose donates a hydrogen bond to the N7 of guanine, while the other receives a hydrogen bond from the N4 amino group of cytosine. The orientation of these two hydrogen bonds suggests that nogalamycin prefers a GC base pair with its aglycon chromophore intercalating at the 5'-side of a guanine (between NpG), or at the 3'-side of a cytosine (between CpN) with the sugars pointing toward the GC base pair. The binding of nogalamycin to DNA requires that the base pairs in DNA open up transiently to allow the bulky sugars to go through, suggesting that nogalamycin prefers GC sequences embedded in a stretch of AT sequences. PMID- 2261475 TI - Three-dimensional model and molecular dynamics simulation of the active site of the self-splicing intervening sequence of the bacteriophage T4 nrdB messenger RNA. AB - The secondary and 3D structure of the active site of the self-splicing T4 nrdB RNA has been modeled on a graphics workstation by use of the suggested 3D arrangement of the active site of the Tetrahymena IVS [Kim, S.H., & Cech, T.R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8788-8792] as a guideline. The initially obtained crude structure was then subjected to molecular mechanics energy minimization and molecular dynamics simulation to relax tensions. In this process the energy decreased considerably and gave a final structure that deviated by 3 A [root mean square (rms)] from the initial structure. The cofactor guanosine (and the competitive inhibitor arginine) was docked to a proposed [Michel, F., Hanna, M., Green, R., Bartel, D.P., & Szostak, J.W. (1989) Nature 342, 391-395] binding site, where it was found to fit rather well. A minor modification of the binding mode easily brought the O3' end of the guanosine within 2 A of the phosphodiester bond where the primary cleavage occurs. PMID- 2261476 TI - Molecular cloning and primary structure of rat testes metalloendopeptidase EC 3.4.24.15. AB - The complete amino acid sequence of rat testes metalloendopeptidase (EC 3.4.24.15) was deduced from the nucleotide sequence of a cDNA clone isolated by screening a rat testes library with a polyclonal antibody raised against a homogeneous preparation of the rat testes enzyme. The correctness of the sequence was verified by N-terminal amino acid sequence analysis of the isolated enzyme and by partial amino acid sequence analysis of three tryptic peptides located near the N-terminus, the middle, and C-terminus of the native protein. The enzyme is composed of 645 amino acids with a molecular weight of 72,985. This value is close to that of the purified rat testes and brain enzyme as determined by polyacrylamide gel electrophoresis under denaturing and reducing conditions and by molecular sieving chromatography. The enzyme contains the putative active-site sequence -H-E-F-G-H- that is homologous to the sequence in the active site of thermolysin and several other related bacterial enzymes, as well as to active site sequences of several mammalian zinc metallopeptidases. No amino acid sequence homology, beyond this active site, was found with thermolysin, a bacterial zinc metalloendopeptidase, nor with several mammalian zinc metallopeptidases. Northern blot hybridization analyses showed the presence of mRNA encoding the enzyme in rat testes, but not in other rat tissues in spite of the finding that enzyme activity is widely distributed in all tissues and that relatively high activities are present in rat brain and pituitary. PMID- 2261477 TI - Comparison of the DNA-alkylating properties and mutagenic responses of a series of S-(2-haloethyl)-substituted cysteine and glutathione derivatives. AB - The mutagenicity of 1,2-dibromoethane is highly dependent upon its conjugation to glutathione by the enzyme glutathione S-transferase. The conjugates thus formed can react with DNA and yield almost exclusively N7-guanyl adducts. We have synthesized the S-haloethyl conjugates of cysteine and glutathione, as well as selected methyl ester and N-acetyl derivatives, and compared them for ability to produce N7-guanyl adducts with calf thymus DNA. The cysteine compounds were found to be more reactive toward calf thymus DNA and yielded higher adduct levels than did the glutathione compounds. Adduct levels tended to be suppressed when there was a net charge on the compound and were not affected by substitution of bromine for chlorine, as expected for a mechanism known to involve an intermediate episulfonium ion. Sequence-selective alkylation of fragments of pBR322 DNA was investigated. The compounds produced qualitatively similar patterns of alkylation, with higher levels of alkylation at runs of guanines. The compounds were also tested for their ability to act as direct mutagens in Salmonella typhimurium TA98 and TA100. None of the compounds caused mutations in the TA98 frameshift mutagenesis assay. In the strain TA100, where mutation of a specific guanine by base-pair substitution produces reversion, all compounds were found to produce mutations, but the levels of mutagenicity did not correlate at all with the levels of DNA alkylation. The ratio of mutations to adducts varied at least 14-fold among the various N7-guanyl adducts examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261478 TI - Structure and oxidation-reduction behavior of 1-deaza-FMN flavodoxins: modulation of redox potentials in flavodoxins. AB - Flavodoxins from Clostridium beijerinckii and from Megasphaera elsdenii with 1 carba-1-deaza-FMN substituted for FMN have been used to study flavin-protein interactions in flavodoxins. The oxidized 1-deaza analogue of FMN binds to apoflavodoxins from M. elsdenii and C. beijerinckii (a.k.a. Clostridium MP) with association constants (Ka) of 1.0 x 10(7) M-1 and 3.1 x 10(6) M-1, values about 10(2) less than the corresponding Ka values for FMN. X-ray structure analysis of oxidized 1-deaza-FMN flavodoxin from C. beijerinckii at 2.5-A resolution shows that the analogue binds with the flavin atoms in the same locations as their equivalents in FMN but that the protein moves in the vicinity of Gly 89 to accommodate the 1-CH group, undergoing displacements which increase the distance between position 1 of the flavin ring and the main-chain atoms of Gly 89 and move the peptide hydrogen of Gly 89 by about 0.6 A. The X-ray analysis implies that protonation of normal flavin at N(1), as would occur in formation of the neutral fully reduced species, would result in a similar structural perturbation. The oxidation-reduction potentials of 1-deaza-FMN flavodoxin from M. elsdenii have been determined in the pH range 4.5-9.2. The oxidized/semiquinone equilibrium (E'0 = -160 mV at pH 7.0) displays a pH dependence of -60 mV per pH unit; the semiquinone/reduced equilibrium (E'0 = -400 mV at pH 7.0) displays a pH dependence of -60 mV per pH unit at low pH and is pH independent at high pH, with a redox-linked pK of 7.4. Spectral changes of fully reduced 1-deaza-FMN flavodoxin with pH suggest that this latter pK corresponds to protonation of the flavin ring system (the pK of free reduced 1-deaza-FMN is 5.6 [Spencer, R., Fisher, J., & Walsh, C. (1977) Biochemistry 16, 3586-3593]. The pK of reduced 1 deaza-FMN flavodoxin provides an estimate of the electrostatic interaction between the protein and the bound prosthetic group; the free energy of binding neutral reduced 1-deaza-FMN is more negative than that for binding the anionic reduced 1-deaza-FMN by 2.4 kcal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261479 TI - D1-D2-cytochrome b559 complex from the aquatic plant Spirodela oligorrhiza: correlation between complex integrity, spectroscopic properties, photochemical activity, and pigment composition. AB - A D1-D2-cyt b559 complex with about four attached chlorophylls and two pheophytins has been isolated from photosystem II of the aquatic plant Spirodela oligorrhiza and used for studying the detergent-induced changes in spectroscopic properties and photochemical activity. Spectral analyses (absorption, CD, and fluorescence) of D1-D2-cyt b559 preparations that were incubated with different concentrations of the detergent Triton X-100 indicate two forms of the D1-D2-cyt b559 complexes. One of them is photochemically active and has an absorption maximum at 676 nm, weak fluorescence at 685 nm, and a strong CD signal. The other is photochemically inactive, with an absorption maximum at 670 nm, strong fluorescence at 679 nm, and much weaker CD. The relative concentrations of the two forms determine the overall spectra of the D1-D2-cyt b559 preparation and can be deduced from the wavelength of the lowest energy absorption band: preparations having maximum absorption at 674, 672, or 670.5 nm have approximately 20, 60, or 85% inactive complexes. The active form contains two chlorophylls with maximum absorption at 679 nm and CD signals at 679 (+) and 669 nm (-). These chlorophylls make a special pair that is identified as the primary electron donor P-680. The calculated separation between the centers of these two pigments (using an extended version of the exciton theory) is about 10 A, the pigments' molecular planes are tilted by about 20 degrees, and their N1-N3 axes are rotated by 150 degrees relative to each other. The other two chlorophylls and one of the two pheophytins in the D1-D2-cyt b559 complex have their maximum absorption at 672 nm, while the maximum absorption of the photochemically active pheophytin is probably at 672-676 nm. During incubation with Triton X-100, the photochemically active complex is transformed into an inactive form with first-order kinetics. In the inactive form the maximum absorption of the 679 nm absorbing Chls is blue shifted to 669 nm. The first-order decay of the photochemical activity suggests that the isolated D1-D2-cyt b559 complex is stable as an aggregate but becomes unstable on dissociation into individual D1-D2-cyt b559 units. PMID- 2261480 TI - Localization of a reactive exofacial sulfhydryl on the glucose carrier of human erythrocytes. AB - Tryptic digestion studies of the human erythrocyte glucose carrier have shown that a reactive and transport-sensitive exofacial sulfhydryl is located in the carboxy-terminal half of the molecule, corresponding to Cys347, Cys421, or Cys429. In the present studies, the erythrocyte glucose carrier labeled on the exofacial sulfhydryl with bis(maleimidomethyl) ether-L-[35S]cysteine was chemically cleaved, either at tryptophans by N-bromosuccinimide or at nonalkylated cysteines by 2-nitro-5-thiocyanobenzoic acid. The resulting fragments were separated by linear gradient polyacrylamide gel electrophoresis, and the labeled fragments were identified by their apparent molecular weight, and by immunoblotting with antibodies to specific regions of the carrier protein. All of the labeled fragments were recognized by an antibody to the carboxy terminus of the carrier, but not by an antibody to a cytoplasmic loop on the C-terminal half of the carrier. The labeled exofacial sulfhydryl was assigned to Cys429, since this is the only residue of the three possibilities which is beyond the expected cleavage sites of the two reagents in the carrier sequence. These results concur with the predictions of hydropathy analysis and will be relevant for studies of how modification of this sulfhydryl affects carrier function, particularly since several other known carrier isoforms lack a corresponding cysteine. PMID- 2261481 TI - Differential scanning calorimetric studies of ethanol interactions with distearoylphosphatidylcholine: transition to the interdigitated phase. AB - It is well established that ethanol and other amphipathic molecules induce the formation of a fully interdigitated gel phase in saturated like-chain phosphatidylcholines (PC's). We have previously shown that the induction of interdigitation in PC's by ethanol is dependent upon the alcohol concentration, the lipid chain length, and the temperature [Nambi, P., Rowe, E. S. & McIntosh, T. J. (1988) Biochemistry 27, 9175-9182]. In the present study, we have used high sensitivity differential scanning calorimetry to investigate the transitions of distearoylphosphatidylcholine between the noninterdigitated and the interdigitated phases. The enthalpy of the L beta' to L beta I transition is approximately half that of the L beta' to P beta' transition which occurs in the absence of ethanol. The reversibility of these transitions has also been investigated by employing both heating and cooling scans in order to establish the most stable phases as a function of temperature and ethanol concentration. It has been demonstrated that the transition to the interdigitated phase is reversible as a function of temperature. Kinetic studies on the reverse transition (L beta I to L beta') demonstrate that this transition can be very slow, requiring weeks to reach completion. The rate depends upon temperature and ethanol concentration. The slow phase changes mean that the lipid can exist for long periods of time in a phase structure which is not the most stable state. The biological significance of this type of lipid behavior is the implication that the phase structure of biological membranes may depend not only on the most stable phase structure of the lipids present but also on the synthetic pathway or other kinetic variables. PMID- 2261482 TI - Site-directed alteration of the active-site residues of histidine decarboxylase from Clostridium perfringens. AB - To clarify the mechanism of biogenesis and catalysis by the pyruvoyl-dependent histidine decarboxylase (HisDCase) from Clostridium perfringens, 12 mutant genes encoding amino acid substitutions at the active site of this enzyme were constructed and expressed in Escherichia coli. The resulting mutant proteins were purified to homogeneity, characterized, and subjected to kinetic analysis. The results (a) exclude all polar amino acid residues in the active site except Glu 214 as donor of the proton that replaces the carboxyl group of histidine during decarboxylation and, since E214I and E214H are nearly inactive, indicate that Glu 214 is the essential proton donor; (b) demonstrate the importance to substrate binding of hydrophobic interactions between Phe-98, Ile-74, and the imidazole ring of histidine, and of hydrogen bonding between Asp-78 and N2 of the substrate; and (c) demonstrate a significant unidentified role for Glu-81 in the maintenance of the active-site structure. The proposed roles of these amino acid residues are consistent with those assigned on the basis of crystallographic evidence to the corresponding residues at the active site of the related HisDCase from Lactobacillus 30a [Gallagher, T., Snell, E. E., & Hackert, M. L. (1989) J. Biol. Chem. 264, 12737-12743]. Of the residues altered, only Ser-97 was essential for the autocatalytic serinolysis reaction by which this HisDCase, (alpha beta)6, is derived from its inactive, pyruvate-free precursor, proHisDCase, pi 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261483 TI - Fluorescent oligopeptide substrates for kinetic characterization of the specificity of Astacus protease. AB - The design of fluorescent N-dansylated oligopeptides based on the tubulin cleavage pattern by Astacus protease yields substrates that are turned over up to 10(5) times faster than those presently available. On the basis of this study, an optimal substrate for Astacus protease contains seven or more amino acids and minimally requires at least five amino acids. Direct examination of the formation and breakdown of the ES complex shows its formation occurs within milliseconds at 25 degrees C. The best heptapeptide substrate, Dns-Pro-Lys-Arg-Ala-Pro-Trp-Val, is cleaved only between the Arg-Ala (P1-P1') bond with kinetic parameters kcat = 380 s-1 and Km = 3.7 x 10(-4) M. The presence of Lys or Arg in the P1 and P2 positions yields high-turnover substrates. In the P3 position, the enzyme prefers Pro greater than Val greater than Leu greater than Ala greater than Gly, following the same order of preference seen in the tubulin cleavage pattern. Substitution of Leu for Ala in P1' and of Ser for Pro in P2' decreases activity by 10(5)- and 10(2)-fold, respectively. In position P3', substitution of Trp for Leu leaves the activity unaltered. However, introduction of the Trp fluorophore greatly enhances the sensitivity of the assay due to a 10-fold increase in indole fluorescence for cleavage of any peptide bond between the tryptophan and the dansyl group. Such an energy-transfer-based assay should have widespread use for detection of neutral proteases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261484 TI - The dissimilar interactions of the calcium antagonist flunarizine with different phospholipid classes and molecular species: a differential scanning calorimetry study. AB - The influence of the class IV calcium antagonist flunarizine on the phase behaviour of different species of the major phospholipid classes of mammalian plasma membranes has been examined using differential scanning calorimetry. We show that it has the ability to substantially influence the phase behaviour of phospholipids. Flunarizine significantly influences the gel to liquid-crystalline transition temperature of phosphatidylserines whilst having little effect on those of the phosphatidylethanolamines tested. The liquid-crystalline to inverted hexagonal phase transition of phosphatidylethanolamines is, however, strongly induced by the presence of flunarizine. Examination of the effect of flunarizine on the phase behaviour of different phosphatidylcholine species revealed an acyl chain dependent influence. Dissimilar results with phosphatidylcholines, phosphatidylethanolamines and phosphatidylserines reveal different locations and ionization states for the drug in the different phospholipid bilayers. These results not only indicate an essential role for the ionization state of the drug in determining drug-phospholipid interactions but also the role of the phospholipid in determining the ionization state of the drug and have important implications for drug-membrane interactions demonstrating that drug interaction with one phospholipid may bear no relation whatsoever to its interaction with another. PMID- 2261485 TI - Effects of neutral and anionic lipids on digalactosyldiacylglycerol vesicle aggregation. AB - We have previously reported that large unilamellar liposomes made from the neutral galactolipid digalactosyldiacylglycerol (DGDG) will aggregate in the presence of monovalent or divalent cations, behavior that would not have been predicted for an uncharged lipid (Webb et al. (1988) Biochim. Biophys. Acta 938, 323-333). In this paper, the effects of including the other major thylakoid lipids on the Mg2+ concentration required for aggregation of DGDG vesicles has been examined. Addition of the neutral, hexagonal-II phase preferring lipid monogalactosyldiacylglycerol (MGDG) to DGDG up to 50 mol% had no effect, suggesting that the MGDG head group is as effective in causing aggregation as the DGDG head group. Addition of 0.5 to 5.0 mol% of either of the two anionic lipids phosphatidylglycerol (PG) or sulfoquinovosyldiacylglycerol (SQDG) inhibited the aggregation of DGDG vesicles, probably by the development of an electrostatic potential. Phosphatidylcholine (PC) in amounts up to 25 mol% did not inhibit or promote aggregation. Vesicles with a composition similar to that of thylakoids (DGDG/MGDG/SQDG/PG, 1:2:0.5:0.5) required 65 mM MgCl2 in the presence of 200 mM KCl, i.e., higher concentrations than are present in the chloroplast stroma. If MGDG made up more than 25 mol% of any combination of lipids, vesicle aggregation could not be reversed by dilution. These results are consistent with cations playing a role in mediating the close approach of bilayers via an effect on head group hydration and head-group interaction between bilayers. PMID- 2261486 TI - Association probabilities between the single chain amphiphiles into a binary mixture in planar monolayers. AB - In this work, we have calculated the probabilities of selfassociation of single chain amphiphile molecules for 36 binary mixtures of molecules having an even number of carbon atoms (from 8 to 24 carbon atoms). The association probabilities depend on the dipole moment of head groups, the length of chains and the mole fraction of the mixture of both types of amphiphile. These calculations are useful for the quantitative and qualitative explanation of the cluster formation on the surface of the mono- or bilayers. PMID- 2261487 TI - Rapid turn-over of plasma membrane sphingomyelin and cholesterol in baby hamster kidney cells after exposure to sphingomyelinase. AB - Plasma membrane sphingomyelin in baby hamster kidney (BHK-21) cells was hydrolyzed with sphingomyelinase (Staphylococcus aureus) and the effects on membrane cholesterol translocation and the properties of membrane bound adenylate cyclase and Na+/K(+)-ATPase were determined. Exposure of confluent BHK-21 cells to 0.1 U/ml of sphingomyelinase led to the degradation (at 37 degrees C) of about 60% of cell sphingomyelin. No simultaneous hydrolysis of phosphatidylcholine occurred. The hydrolysis of sphingomyelin subsequently led to the translocation (within 40 min) of about 50-60% of cell [3H]cholesterol from a cholesterol oxidase susceptible pool to an oxidase resistant compartment. The translocation of [3H]cholesterol from the cell surface to intracellular membranes was accompanied by a paralleled increase in [3H]cholesterol ester formation. When cells were first exposed to sphingomyelinase (to degrade sphingomyelin) and then incubated without the enzyme in serum-free media, the mass of cell sphingomyelin decreased initially (by 60%), but then began to increase and reached control levels within 3-4 h. The rapid re-synthesis of sphingomyelin was accompanied by an equally rapid normalization of cell [3H]cholesterol distribution. The re formation of cell sphingomyelin also led to a decreased content of cellular [3H]cholesterol esters, indicating that unesterified [3H]cholesterol was pulled out of the cholesterol ester cycle and transported to the cell surface. Exposure of BHK-21 cells to sphingomyelinase further led to a dramatically decreased activity of ouabain-sensitive Na+/K(+)-ATPase, whereas forskolin-stimulated adenylate cyclase activity was not affected. The activity of Na+/K(+)-ATPase returned to normal in parallel with the normalization of cell sphingomyelin mass and cholesterol distribution. We conclude that sphingomyelin has profound effects on the steady-state distribution of cell cholesterol, and that manipulations of cell sphingomyelin levels directly and reversibly affects the apparent distribution of cholesterol. Changes in the lipid composition of the plasma membrane also appears to selectively affect important metabolic reactions in that compartment. PMID- 2261488 TI - Substantial glucose leakage from liposomes on filters and upon molecular-sieve chromatography in determinations of reconstituted glucose-transport activity and liposome volumes. AB - Transport-protein activities are often determined by procedures that involve isolation of liposomes containing the transported radioactive solute. We determined the activity of the human red cell glucose transporter in liposomes and, by similar procedures, internal volumes of liposomes. For these purposes, we isolated freeze-thawed liposomes loaded with [14C]glucose, either by filtration on cellulose-nitrate and cellulose-acetate filters, or by chromatography on Sephadex. The interaction of liposomes with filters caused substantial leakage of [14C]glucose. About half of the internal [14C]glucose was released on the filters from glucose-transporter liposomes with inhibited transport. Chromatography at high flow rate provided higher and more accurate values than did the filtration procedure. Leakage corrections could be made by use of flow-cell scintillation elution profiles. The ratios between the corrected chromatographic volume values and the filtration values were 1.4-3.0 for liposomes without protein, 2.4-4.0 for glucose-transporter liposomes and 3.6-7.9 for liposomes with several human red cell integral membrane proteins. The D-glucose equilibrium exchange with glucose transporter liposomes at 50 mM D-glucose was 2.0 nmol D-glucose per microgram transporter per second as determined by use of chromatography at high flow rate. The filtration procedure gave only 0.6 nmol.microgram-1.s-1 due to the [14C]glucose leakage. In our experiments, the chromatographic procedure thus proved superior. PMID- 2261489 TI - Heat-induced alterations in monkey erythrocyte membrane phospholipid organization and skeletal protein structure and interactions. AB - Rhesus monkey erythrocytes were subjected to heating at 50 degrees C for 5-15 min, and the heat-induced effects on the membrane structure were ascertained by analysing the membrane phospholipid organization and membrane skeleton dynamics and interactions in the heated cells. Membrane skeleton dynamics and interactions were determined by measuring the Tris-induced dissociation of the Triton insoluble membrane skeleton (Triton shells), the spectrin-actin extractability at low ionic strength, spectrin self-association and spectrin binding to normal monkey erythrocyte membrane inside-out vesicles (IOVs). The Tris-induced Triton shell dissociation and spectrin-actin extractability were markedly decreased by the erythrocyte heating. Also, the binding of the heated erythrocyte membrane spectrin-actin with the IOVs was much smaller than that observed with the normal erythrocyte spectrin-actin. Further, the spectrin structure was extensively modified in the heated cells, as compared to the normal erythrocytes. Transbilayer phospholipid organization was ascertained by employing bee venom and pancreatic phospholipases A2, fluorescamine, and Merocyanine 540 as the external membrane probes. The amounts of aminophospholipids hydrolysed by phospholipases A2 or labeled by fluorescamine in intact erythrocytes considerably increased after subjecting them to heating at 50 degrees C for 15 min. Also, the fluorescent dye Merocyanine 540 readily stained the 15-min-heated cells but not the fresh erythrocytes. Unlike these findings, the extent of aminophospholipid hydrolysis in 5-min-heated cells by phospholipases A2 depended on the incubation time. While no change in the membrane phospholipid organization could be detected in 10 min, prolonged incubations led to the increased aminophospholipid hydrolysis. Similarly, fluorescamine failed to detect any change in the transbilayer phospholipid distribution soon after the 5 min heating, but it labeled greater amounts of aminophospholipids in the 5-min-heated cells, as compared to normal cells, after incubating them for 4 h at 37 degrees C. These results have been discussed to analyse the role of membrane skeleton in maintaining the erythrocyte membrane phospholipid asymmetry. It has been concluded that both the ATP-dependent aminophospholipid pump and membrane bilayer skeleton interactions are required to maintain the transbilayer phospholipid asymmetry in native erythrocyte membrane. PMID- 2261490 TI - The effect of surfactants on the aggregation state of amphotericin B. AB - We have studied the effect of two surfactants, one non-ionic, lauryl sucrose (LS) and the other ionic, sodium deoxycholate (DOC), on the aggregation state of amphotericin B (AmB) and its selectivity towards ergosterol and cholesterol. It is shown that the addition of these surfactants has very similar effects on the AmB micelles. Below the critical micellar concentration of the surfactants, mixed micelles with AmB are first formed as a result of the penetration of the surfactant molecules into the AmB micelles. At higher concentrations of the surfactant molecules, the micellar structure is completely destroyed and AmB is found as monomers in solution. When the concentration of the surfactant is further increased, micelles of the surfactant molecules are built up, AmB remaining in monomeric form. However, the critical micellar concentration of LS is modified by the presence of AmB in solution, while that of DOC is not affected, thereby indicating that the interactions of AmB with LS are stronger than those of DOC with AmB. We also show that both surfactants enhance the selectivity of the AmB binding to sterols at exactly the concentrations of the surfactants which induce the monomerization of the antibiotic. It is observed that the maximal selectivity is found at a concentration of the surfactants corresponding to their particular CMC in presence of the antibiotic. PMID- 2261491 TI - Effect of FCCP on tight junction permeability and cellular distribution of ZO-1 protein in epithelial (MDCK) cells. AB - The effect of the uncoupler of oxidative phosphorylation, FCCP (carbonylcyanide p trifluoromethoxyphenylhydrazone), on the tight junction of Madin-Darby canine kidney cells was examined. FCCP induced an abrupt decrease in the transepithelial electrical resistance of the confluent monolayers over a period of 20 s. When FCCP was withdrawn from the incubation medium, the monolayer resistance recovered to close to the original level in less than 2 h. Staining of the tight junction associated protein ZO-1 showed that the changes in transepithelial electrical resistance were accompanied by a diffusing of the protein away from cell peripheries and a reconcentration to the tight junction areas following resistance recovery. Intracellular pH was decreased by FCCP on a similar time scale with no obvious changes in ATP levels over this time-course. These data suggest that the uncoupler FCCP has a profound effect on tight junction permeability and cellular distribution of the tight junction protein ZO-1 in the epithelial cells and that it probably acts by breaking down proton gradients and altering intracellular pH. PMID- 2261492 TI - Regulation of gene expression by the thyroid hormone receptor. PMID- 2261493 TI - The structure, metabolism and function of the carcinoembryonic antigen gene family. PMID- 2261494 TI - Proteoglycans in haemopoietic cells. AB - Proteoglycans are produced by all types of haemopoietic cells including mature cells and the undifferentiated stem cells. The proteinase-resistant secretory granule proteoglycan (serglycin; Ref. 14), is the most prevalent and best characterised of these proteoglycans. Although its complete pattern of distribution in the haemopoietic system is unknown, serglycin has been identified in the mast cells, basophils and NK cells, in which secretion is regulated, and in HL-60 cells and a monocytoid cell line (Kolset, S.O., unpublished data) in which secretion is constitutive. Proteinase-resistant proteoglycans have been detected in human T-lymphocytes and murine stem cells (FDCP-mix) and the core proteins may be closely related to serglycin. A variety of glycosaminoglycan chains are assembled on the serglycin protein and it is likely that this class of proteoglycan can carry out a wide variety of functions in haemopoietic cells including the regulation of immune responses, inflammatory reactions and blood coagulation. There is strong evidence that in mast cells, NK cells and platelets, the proteoglycans are complexed to basic proteins (including enzymes and cytolytic agents) and amines in secretory granules and such complexes may dissociate following secretion from the cell. The stability of the complexes may be regulated by the ambient pH which may be acidic in the granules and neutral or above in the external medium. However, proteinase-proteoglycan complexes in mast cell granules seem to remain stable after secretion and it has been proposed that the proteoglycan regulates activity of proteinases released into the pericellular domain. The functions of proteoglycans which are constitutively secreted from cells are less clear. If cells have no requirement for storage of basic proteins why do they utilise the same design of proteoglycan as cells which accumulate secretory material prior to regulated release? We should stress that the so called constitutive secretory pathway has been identified in haemopoietic cells in culture, which are usually maintained and grown in the presence of mitogenic factors (e.g., IL-2, IL-3). the cells are therefore activated and it has not been established that continuous proteoglycan secretion occurs in quiescent cells circulating in the peripheral blood. It is possible that lymphocytes, monocytes and macrophages, in which the constitutive secretion pathway operates in vitro, may store proteoglycan in vivo unless stimulated by mitogens or other activating agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2261495 TI - Tumorigenesis by slow-transforming retroviruses--an update. PMID- 2261496 TI - A new automated method of image analysis: comparison of ciliary and flagellar beats. AB - A new automated method of image analysis of sperm flagellar (human) and cilia (Dunaliella) bends is developed. This method permits an automatic determination of the line characterizing the flagellum. Two dynamic parameters are measured: the wave propagation velocity and the wave curvature radius. The data reveal similar patterns in the propagation of the principal and reverse waves between flagelated and ciliated cells. Conversely, differences are seen in principal wave curvature due perhaps to the presence of periaxonemal structures in the flagellum, absent in cilium. The identical patterns of reverse wave curvaturei in both systems may be linked to axonemal limitations. PMID- 2261497 TI - Poiseuille Medal lecture. Capillary flow: past, present, and future. PMID- 2261498 TI - On mucociliary transport. AB - The periodically changing flow pattern in the mucus layer which lies between the ciliary tips and the transported load is discussed and analyzed. The resulting energy dissipation per cilium is estimated, as is the energy dissipated per cilium in the periciliary fluid. The rate of supply of energy to each cilium by far exceeds these two loss rates. It is shown why the elastic character of mucus is important for good momentum transfer from cilium to load and for good load carrying properties. Fast flow requirements upon secretion of mucus, on the other hand, make it desirable that elasticity and viscosity be low as possible. A compromise is needed and the rheological character of mucus is matched to satisfy these opposing demands. PMID- 2261499 TI - Rheological aspects of red blood cell aggregation. AB - The rheological aspects of red blood cell aggregation include molecular phenomena, cell viscoelasticity, and bulk flow rheology. At the molecular level, rates at which bonds are formed and broken, the chemical energy liberation from bond formation, the elasticity of the cross-bridges and lateral mobility of cross linking molecules must all be considered for a complete description of bond formation and distribution. Lateral migration of binding molecules occurs due to diffusion in the surface of the membrane but may also be influenced by the stresses in the membrane during separation of adhering cells. In red blood cell disaggregation, fluorescent probes have shown concentration of ligands in the region of contact close to the line of separation. The chemical potential decrement that occurs when a bond is formed provides the energy source that may deform red blood cells in the process of aggregation. The degree of aggregation and the extent of cell deformation depends on the viscoelastic properties of the cell as well as the dynamics of bond formation and repulsive potential of surface charges present, which is governed by an equation representing a balance of these energies. In flowing blood, the hydrodynamic forces applied by the plasma and surrounding cells must be added to the bond forces and elastic response of the cell. Under sufficiently strong aggregation, plug flow or large aggregates may result. At high shear rates, aggregation may be prevented due to the small contact time and high shear stresses so that no effects of aggregation may be observed. At intermediate shear stresses, transitory contact, adhesion and disaggregation may occur between neighboring cells. Such phenomena have not been analyzed in detail, but simplified models suggest that plug-like flow can occur due to hydrodynamic cell-cell interaction even when cells are not aggregated. PMID- 2261500 TI - Molecular basis of red cell membrane rheology. Part 1. AB - The biorheological properties and behavior of red blood cells (RBCs), as other types of cells, have a biochemical and molecular basis. The shape maintenance and deformability of RBCs depend on the structural and functional integrity of the membrane proteins. These proteins are composed of transmembrane proteins inserted in the lipid bilayer, the skeletal proteins forming a network lining the membrane endoface, and the linking proteins which link together the other two types of proteins to form a three-dimensional protein structure to effect the complex and intricate biorheological functions of the RBC. The application of molecular biological techniques has led to the establishment of the molecular structures of all major RBC membrane proteins and generated insights into the nature and energy of protein interactions in the membrane. Abnormalities or deficiencies of these proteins in hereditary disorders in humans and animals have offered opportunities to assess the rheological significance of each of these proteins and their interactions. Parallel molecular biological and biorheological studies on RBC membranes under a variety of conditions can provide the fundamental information required for theoretical modeling of RBC membrane rheology at the molecular level. Such interdisciplinary research will contribute to not only the elucidation of normal rheology of RBCs and other types of cells, but also the understanding of pathorheology of their disorders and the development of new methods of diagnosis and treatment. PMID- 2261501 TI - Erythrocyte shape and volume changes caused by an inhibitor of the glucose and anion transporters. AB - Light scattering measurements and scanning electron microscopy show that p azidobenzylphlorizin (p-AzBPhz) causes changes in the shape and volume of human erythrocytes by at least two, dose-dependent mechanisms: At nominal concentrations above 5 microM, the azide induces cell swelling by either enlarging a pre-existent channel or by creating pores between phase boundaries of the membrane through which salt and water enter, but sucrose remains excluded. However, over the range 0.03 to 0.3 microM, in either isosmotic NaCl or KCl media, when fewer than 1 million molecules of azide are bound per cell, the ligand causes membrane deformations that convert discocytes into cells resembling stage 2 echinocytes. Whereas a cell volume increase of about 10% accompanies these shape changes, (microhematocrit and electronic cell sizing measurements), no net influx of either Na+ or K+ during this stage of swelling was detectable. These cell alterations take place at p-AzBPhz concentrations which concurrently inhibit both chloride and 3-methoxyglucose equilibrium exchange transport. The results may indicate that when the membrane impermeable p-AzBPhz interacts with the anion and/or sugar transporter, some trans-membrane perturbation occurs which alters the cytoskeleton. PMID- 2261502 TI - Regulation of red cell membrane deformability and stability by skeletal protein network. AB - The skeletal protein network of the red blood cell is thought to be important in regulating such membrane functions as deformability and stability. In the present study, we measured membrane deformability and stability of the resealed ghosts using an ektacytometer, a laser diffraction method, and identified the functional role of protein 4.1 and that of Ca2+ and calmodulin in maintaining membrane stability. To obtain direct evidence for a crucial role of protein 4.1 in maintaining membrane stability, we reconstituted protein 4.1-deficient membranes with purified protein 4.1. Although native membranes deficient in protein 4.1 had marked reduction in membrane stability, reconstitution with increasing concentrations of purified protein 4.1 resulted in progressive restoration of membrane stability, providing direct evidence that protein 4.1 is essential for normal membrane stability. To determine if Ca2+ and calmodulin could modulate membrane properties, we measured membrane stability and deformability of resealed ghosts prepared in the presence of varying concentrations of Ca2+ and physiologic concentrations of calmodulin. Our data show that Ca2+ concentrations in the range of 1 to 100 microM can markedly decrease membrane stability only in the presence of calmodulin, but not in its absence. In contrast, deformability decreased only at Ca2+ concentrations higher than 100 microM, and calmodulin had no effect. Examination of the the effects of Ca2+ and calmodulin on various membrane protein interactions has enabled us to suggest that the observed changes in membrane stability may be partly related to the effects of Ca2+ and calmodulin on spectrin protein 4.1-actin interaction. PMID- 2261503 TI - Fluorescence depolarization method in the study of dynamic properties of blood cells. AB - Fluorescence polarization is the most commonly used method to approach a property of cell membrane, the so-called "fluidity". Whether time resolved determinations may be of potential interest to get precise information on the behaviour of fluorescent probes incorporated into biological membranes, steady state measurements are still the most accessible for biologists. Steady-state anisotropy value may be considered as a semi-quantitative indication of the cohesion of the lipid chains. However, meaningful interpretation of the anisotropy values requires a careful sample preparation and a suitable use of fluorescent probes. This paper reviews the properties and uses of several hydrophobic membrane fluidity probes. In the case of intact cells, the potential interest of the association of fluorescence polarization with quenching fluorescence method in giving information on the "actual" membrane fluidity is outlined. PMID- 2261504 TI - Analysis for the molecular motion of phospholipid bilayer with picosecond fluorometry. AB - The viscosity and the molecular motion of phospholipid molecule in biological and artificial phospholipid bilayers were studied using picosecond fluorescence depolarization method with rod-like fluorophore, DPH. From the relationship between the viscosity in the lipid bilayer and the free space of phospholipid acyl-chain, it is concluded that the viscosity is determined mainly by the range of wobbling motion of the acyl-chain. Motion of polar head group was also measured by the same method with a newly synthesized fluorescent phospholipid, dipalmitoyl-phosphatidyl-umbelliferone. The rate and the range in the motion of head group were faster and larger than those of acyl-chain and gave the viscosity of head group layer to be 0.03 poise, which was about one tenth of that of acyl chain layer in the liquid crystalline phase. This fact indicates that the head group layer would not resist the lateral diffusion of molecules in membrane and that the lateral diffusion rate of molecules could be estimated from the viscosity in the acyl-chain layer. PMID- 2261505 TI - Visible spectroscopic technique for flowing erythrocytes in capillary. AB - An optical spectroscopic system for determining the rate of oxygen release from flowing erythrocytes in microvessel is developed. The apparatus consists of following units attached to an inverted microscope. 1) A scanning spectrophotometer, equipped with a grating and a photon counter, was connected to an eyepiece of the microscope through a narrow light-guide, as to obtain the absorption spectrum (wave length range: 450-650 nm) of a focused spot (phi = 7 microns). 2) The velocity of erythrocyte flow was measured by dual-spots cross correlation method, using two photomultipliers (connected to A/D converter and microcomputer) with two light-guides inserted into another eyepiece. 3) The diameter of vessel was estimated from digitized video-images, using a color image processor. The ability of the apparatus was tested with (a) hemoglobin solution, (b) flowing erythrocyte suspension and (c) capillaries of rat mesentery. The rate of oxygen release through the vessel wall was calculated. PMID- 2261506 TI - Pentoxifylline pretreatment decreases the pool of circulating activated neutrophils, in-vivo adhesion to endothelium, and improves survival from hemorrhagic shock. AB - Recent research suggests that polymorphonuclear neutrophils (PMNs) play an important role in ischemic organ injury by adhesion to the endothelium and by expression of cytotoxicity via oxygen free radical formation. The number of activated circulating PMNs as measured by the reduction of nitroblue tetrazolium (NBT-positive PMNs) were shown to be closely associated with the trend towards irreversibility in hemorrhagic shock. Our objective was to investigate the effect of pentoxifylline (PTX) on two aspects of the PMN mediated injury: (a) adhesion to the endothelium, and (b) spontaneous circulating PMN activation as a risk factor in a Wiggers type hemorrhagic shock protocol (35 mmHg mean arterial pressure for 90 minutes). The adhesion energy was estimated from the relative rolling velocity of individual PMNs on the endothelium of post-capillary venules in the rat mesentery before and after PTX treatment. The results indicate: (1) that PTX administration leads to a gradual reduction of the adhesion energy in a dose range between 1 to 100 mg/kg, and (2) it was possible to reduce significantly the spontaneous PMN activation in rats pretreated with PTX orally for at least 6 days (40 mg/kg per day). Although there were no significant differences in the PMN count between the PTX and the control group, the number of circulating NBT-positive PMNs before bleeding, as well as during the hypotensive period, was significantly lower in the PTX than in the control group. The 24-hour survival rate after hemorrhagic shock was improved from 50% in the untreated controls to 91% in the PTX group. These results suggest that manipulation of the circulating pool of PMNs by an agent that decreases the number of activated cells and reduces PMN adhesion to the endothelium, can significantly improve survival in this shock model. PMID- 2261507 TI - Consequences of neutrophil adhesion to physiological and pathological targets. AB - The ability of neutrophils to adhere in a coordinated and reversible manner to the endothelium and other tissular components is crucial to their chemoattractant induced locomotion towards relevant targets. Opsonins play a major role in the killing effect of neutrophils by inducing close adherence between the neutrophil and the target, thus maximizing the effect of the reactive oxygen species released by the stimulated neutrophils. Reactive oxygen species are released together with degradative enzymes and other killing proteins associated with neutrophil degranulation. This targeted neutrophil activity kills invading microorganisms but, in a similar way, may be harmful to organs, cells and molecules that have been altered in some way or are involved in immune reactions. In some other pathological situations where body fluids contain proinflammatory agents, neutrophils may behave in a nontargeted and inappropriate manner. In such cases, adherence is often increased, thus slowing locomotion. Moreover, inflammatory agents often prime neutrophils for the oxidative burst induced by chemoattractants or other stimuli. The combined slow locomotion and hypersensitivity of primed neutrophils leads to a premature release of killing substances which may affect blood components, vascular cells, connective tissue or whole organs. Any disturbance of neutrophil adherence is thus potentially harmful and must be recognized and suitably treated. PMID- 2261508 TI - Leukocyte adhesion to endothelial cells. AB - The adhesion of leukocytes to endothelium is a physiological phenomenon which is the first step for leukocyte emigration. The adhesion can be dramatically increased in pathological situations such as inflammation and vascular diseases. The molecular basis of leukocyte-endothelium interaction has been largely investigated in the last ten years. Using monoclonal antibodies it is possible to characterize the leukocyte adhesion molecule (LeuCAM) also named CD11/CD18 complex. These molecules responsible for leukocyte adhesion are heterodimers consisting of a common beta subunit and different subunit CD11a/CD18 corresponding to LFA-1; CD11b/CD18 to Mac1/Mol; CD11c/CD18 to GP150-95. Beside these receptors, other leukocyte structures such as the fibronectin receptors are involved in the adhesive process. On the endothelial cell side specialized structures implicated in leukocyte adhesion have been identified. Structures like Intercellular Adhesion Molecule (ICAM) are expressed on endothelial cells in the absence of stimulation, while other receptors Endothelial Leukocyte Adhesion Molecule (ELAM) are only detectable on activated endothelial cells. Cytokines such as IL-1 induced the expression of ELAM, increased the number of ICAM and Human Leukocyte Antigens (HLA) DR, DP, DQ. In various pathological circumstances, namely extracorporeal circulation, Acute Respiratory Distress Syndrome (ARDS), hypercholesterolemia and diabetes mellitus increased leukocyte adhesion has been reported and is potentially responsible for vascular damage. Therefore, the modulation of leukocyte-endothelial cell interactions is a possible target for antithrombotic and antiatherosclerotic therapy. PMID- 2261509 TI - Mechanisms of leukocyte adhesion. AB - The interaction between granulocytes and endothelial walls may be influenced by the blood flow. This possibility was investigated by studying the influence of fluid flow on the adhesion and detachment of 51Cr-labeled rat granulocytes interacting with protein-coated glass surfaces. It is concluded that: i) Adhesion is markedly decreased when the wall shear rate becomes higher than about 20 s-1. ii) Pretreating glass with concanavalin A or polylysine significantly decreased adhesion, whereas fibronectin had little effect on binding. iii) Very high flow rates (about one thousandfold higher than those compatible with bond formation) were required to provoke substantial detachment of substrate-bound cells. iv) Coating glass with laminin or polylysine decreased binding strength whereas fibronectin or concanavalin A did not substantially influence this parameter. v) Exposing granulocytes to phorbol myristate acetate might increase the cell ability to form strong adhesions, whereas labile adhesion was unaffected or even decreased by this treatment. PMID- 2261510 TI - Flow cytometry analysis of human neutrophils labeled with rhodamine phalloidin: effect of pentoxifylline. AB - Pentoxifylline (PTX) has been reported to enhance the early accumulation of neutrophils at the site of Staphylococcus aureus subcutaneous infection in mice (1) and to stimulate in vitro PMN chemotaxis, particularly under dense agarose (2). Among the biochemical events contributing to chemotaxis are actin polymerization (3). The membrane cytoskeleton is believed to control the lateral mobility of integral membrane proteins as well as influencing cell shape and mobility. Thus, pharmacological modulations of neutrophil chemotaxis may be related to an effect of the pharmacological agents on the membrane cytoskeleton. The present study was designed to characterize the effect of PTX on actin polymerization of freely-suspended PMN before and after stimulation by the chemotactic factor f-MLP. We used flow cytometry to determine the proportion of actin in the filamentous form, and Rhodamine-Phalloidin as fluorescent probe (4). PTX decreased actin polymerization in response to stimulation by f-MLP. The reduction in F-actin by PTX was higher in the samples with higher activation ratios as compared with untreated PMN. PMID- 2261511 TI - New pharmacological studies with pentoxifylline. AB - Polymorphonuclear (PMN) overactivation plays a critical role in microcirculation as well as in conditions such as multiorgan failure (MOF). Pentoxifylline has been shown to prevent PMN activation by endotoxin and cytokines such as TNF alpha and IL-1. In addition, MOF induced by IL-2 in animals can be prevented by pentoxifylline. The present studies evaluated two aspects of PMN activation and pentoxifylline interaction. The first was the time sequence for pentoxifylline prevention of TNF alpha activation and the second was the activity of pentoxifylline on amphotericin B activation of PMNs. TNF alpha activation of PMNs is blocked by pentoxifylline when cells are exposed to pentoxifylline prior to TNF alpha or after TNF alpha. Amphotericin B activation of PMNs was demonstrated by a decreased chemotaxis, increased chemiluminescence, and increased PMN spreading. In all conditions, pentoxifylline decreased amphotericin B activation of PMNs. These results suggest that pentoxifylline can reverse cytokine activation of PMNs and that pentoxifylline may alter some of the toxic effects of amphotericin. PMID- 2261512 TI - Development of an in vitro model of primate cervical goblet cells. AB - Mucins, are densely packed in secretory granules of goblet cells. Upon exocytosis they undergo massive hydration that results in the formation of the mucus gel. Because the mucin polymer network is held together by tangles and low energy bonds, the rheological properties of this gel are mainly determined by the degree of postexocytotic hydration. Hydration in mucus is governed by a Donnan equilibrium as it is driven by electrostatic interaction among the polyionic charges of the mucins and other fixed polyions. Although, variations of charge density of the mucin polymer could be an efficient physiologic mechanism to control the rate of mucus hydration and rheology, this subject has not been investigated. In here we describe a primary tissue culture system of cervical goblet cells of the monkey uterus. This preparation allows to measure directly the kinetic of hydration of exocytosed mucins. Because the physicochemical parameters of the bathing medium can be effectively controlled, variations in the kinetic of mucins swelling upon exocytosis, can be used as a convenient indicator of fluctuations of charge density in secretory products. Since the cervical mucosa readily respond to endocrine influences, this preparation can provide a useful model to study the effect of hormones or other transmitters on polyionic charge density of secretory product. PMID- 2261513 TI - Diversity of the peptide moiety of human airway mucins. AB - A lambda gt11 cDNA library constructed from human tracheal mucosa was screened with rabbit antibodies raised to chemically deglycosylated pronase glycopeptides from bronchial mucins. This library allowed us to select 20 positive clones. The total or partial nucleotide sequences of 14 of them were classified in three different types of organization or families. Antibodies purified from total immuneserum on each positive clone were specific either of goblet cells or goblet cells and mucous cells, showing a differential cellular expression of the peptide axis of mucins. The use of each type of nucleic probe in Northern blot analysis confirmed the existence of a great heterogeneity of the RNAs contributing to a great peptide heterogeneity. PMID- 2261514 TI - Modification of mucin gene expression in the airways of rats exposed to sulfur dioxide. AB - The molecular mechanisms mediating mucous cell metaplasia and hypersecretion in the respiratory tract are unknown. Previous work suggests that mucous metaplasia requires the induction of mucin gene expression. We are investigating this possibility by monitoring steady state levels of mucin mRNA in a model of mucous cell metaplasia induced by SO2 exposure. Male Sprague Dawley rats were exposed to 400 ppm SO2 gas in air for 3 h per day, 5 days per week for 0,1,2, or 3 weeks. Sham controls were exposed to air under similar conditions. After 3 weeks, morphological changes were apparent in the epithelium of SO2 exposed rats at all levels from the trachea to the distal airways. The epithelial thickness increased, as well as the number and size of glands in the trachea. Epithelial mucous (goblet) cells increased from 0 to 4.5 per mm in the trachea, 0.2 to 6.2 per mm in the main stem bronchi, and 0.2 to 22.7 per mm in the distal airways (mean values obtained for 3-6 tissue blocks per airway level per condition). In parallel experiments, we used SMUC41, a 950 bp human intestinal cDNA to isolate a human airway cDNA, HAM-1 from a cDNA library constructed in bacteriophage from human bronchial poly A+RNA. HAM-1 is a 90 bp cDNA encoding a threonine- and proline-rich peptide with 96% homology to the human intestinal cDNA SMUC-41. Next we probed total and poly A+ airway RNA from rats in each exposure condition with SMUC-41 or HAM-1. Blots were then stripped and reprobed with cDNA encoding beta actin. Densitometry values normalized for the amount of RNA loaded per lane (as determined by actin hybridization intensity) showed that mucin mRNA increased 8-9 fold as a function of SO2 exposure. This is consistent with the possibility that mucin gene transcription is induced by SO2 exposure, and may represent a primary event in the development of mucous metaplasia and hypersecretion. PMID- 2261515 TI - Association of lipids with mucins may take place prior to secretion: studies with primary hamster tracheal epithelial cells in culture. AB - Confluent cultures of hamster tracheal surface epithelial (HTSE) cells are highly enriched with secretory cells and secrete mucins. Ultrastructural studies of cellular localization of these mucins show that mucins are found not only inside secretory granules but also on the apical surface of secretory cells during active secretion, and secreted mucins are highly associated with lipids. In the present communication, we analyzed lipids associated with both cellular and secreted mucins following metabolic radiolabeling of these cultured cells with [3H]palmitic acid. We found that profiles of lipids associated with both cellular and secreted mucins are almost identical not only qualitatively but also quantitatively. It is concluded that the lipid association with mucins seems to take place before secretion. The origin of the cell surface-bound mucins is discussed. PMID- 2261516 TI - Wettability of polymers by mucin aqueous solutions. AB - The wettability of poly(methyl methacrylate) and polyethylene by water and aqueous mucin solutions have been studied by sessile drop and under-water captive air bubble contact angles, respectively. From the sessile drop and octane under water contact angles the polymer-water interfaces have been characterized in terms of works of adhesion and acid-base (polar) interactions. A large water-air contact angle hysteresis observed with poly(methyl methacrylate) surfaces has been attributed to side-chain beta relaxations of polymer ester methyl groups. The wettabilities of the polymers by mucin aqueous solutions have been studied as a function of protein concentration and related to the surface tensions. A positive slope of adhesion tension vs surface tension line, characteristic of polar surfaces, was found with poly(methyl methacrylate). By contrast, a change in the slope, explained as a change in mucin relative adsorption densities at solid/liquid and solid/vapour interfaces, was observed with polyethylene. This adhesion tension behavior appeared to be in agreement with previous data we have published concerning the quantity and state of mucin which are adsorbed to polymers characterized by different surface properties. PMID- 2261517 TI - Tracheal mucus rheology and epithelial potential difference in two day old puppies. AB - The transepithelial potential difference (PD) value represents an integral of ion fluxes across the epithelium, and relates to the regulation of airway fluid. We studied six healthy two day old husky puppies for their tracheal mucus rheology and bioelectric properties, since this data in newborns are still unknown. PD ( mV, epithelium vs. subcutaneous space) was measured using the agar bridge technique in two locations - lower trachea and subglottic region. For the rheological analysis, the magnetic microrheometer was employed; data are presented as mechanical impedance log G* and loss tangent tan delta (1 rad/s). The mucus collection rate (mg/min) and the solid content (%) were determined by gravimetry. Mucociliary clearability, normalized to frog mucus, (MCFP) was determined directly by the frog palate method; a cough clearability index (CCI) was computed from simulated cough machine data obtained with mucus-like gels. The mucus collection rates and PD values were considerably lower than those observed in adult dogs; the mechanical impedance values were also reduced in comparison with adult data. The PD profile within the trachea (-13.9 +/- 1.2 mV lower trachea vs. -18.4 +/- 1.4 mV subglottical, i.e. more negative subglottically), however, is similar to that observed in adult dogs. Intratracheal profiles in mucus collection rate and mucus rheology were also comparable between puppies and adult dogs. The low collection rates in puppies, particularly in lower trachea, could indicate either reduced mucus volume or slower clearance. PD and collection rate correlated very strongly (r = 0.82, p = 0.0003). PD also correlated negatively with log G* (r = 0.73, p = 0.003) and positively with tan delta (r = 0.58, p = 0.03). MCFP and % solids correlated positively (r = 0.84, p = 0.0012), in contradistinction to the usual relationship, perhaps due to the presence of non-glycoprotein components that do not contribute to crosslink formation. The apparent maturation of airway bioelectric properties, mucus collection rate and mucus viscoelasticity are all consistent with the maturation of mucociliary clearance, which has previously been reported. PMID- 2261518 TI - Ciliary adaptations for the propulsion of mucus. AB - The cilia that propel mucus are specialised for the function in their arrangement, length, some details of structure, beat pattern, beat cycle characteristics, metachronal coordination, local control of beat rate by response to mechanical stimulation and generalised control of beat rate by neurohormones. These features are matched to the properties of the visco-elastic mucus gel that is propelled at the ciliary tips above a low-viscosity periciliary layer whose depth must be regulated within defined limits. PMID- 2261519 TI - Regulation of ciliary activity in the mammalian respiratory tract. AB - A computer-assisted transillumination, photoelectronic technique has been used to measure the beat frequency of cilia of rabbit tracheal cells grown in culture. When ciliated cells are mechanically stimulated with a microprobe the cells respond rapidly by increasing the beat frequency of their cilia. This mechanosensitive response is not limited to the stimulated cell, but is communicated in all directions to neighboring cells. To characterize the progression of this communicated response we used an automated computer-assisted imaging system to examine high-speed films of responding cells. The time it takes for the response to be transmitted between cells is slow (1-3 sec) with each cell responding after a lag-time that is proportional to the distance of the cell from the stimulated cell. We have confirmed that gap junctions are present between cells and that adjacent or non-adjacent ciliated, as well as non-ciliated, cells are electrically coupled. To correlate the mechanosensitive response with intracellular calcium fluxes we have used fura-2, a calcium-specific fluorescent dye, and digital video microscopy. Mechanical stimulation of the cultured ciliated cells, in the presence of extracellular calcium, resulted in an initial increase in intracellular calcium, which was communicated to neighboring cells. Without extracellular calcium, mechanosensitivity of cultured cells was lost and a small decrease in intracellular calcium was observed in the stimulated cell. However, neighboring cells still displayed an increase in intracellular calcium. The time course and general pattern of calcium increase in adjacent cells was similar to the responses in ciliary activity produced by mechanical stimulation. Ciliary beat frequency is also elevated by beta-adrenergic drugs independently of mechanosensitivity. These responses are important because they could provide a dual regulatory mechanism for the control of mucus transport. Adrenergic agonists could provide non-specific control by increasing ciliary activity throughout the airways while mechanosensitivity could provide local control by increasing activity in those regions of heavy mucus load. PMID- 2261520 TI - Ciliary activity under normal conditions and under viscous load. AB - Ciliary metachronism and motility were examined optically in muco-ciliary tissue cultures from three different systems: a) frog's palate epithelium, b) frog's oesophagus, and c) human nasal polyps. In addition, lateral cilia of Mytilus edulis (water transporting cilia) were examined. It was revealed that the degree of synchronization between muco-ciliary systems is lower than that of water transporting cilia. There are no significant differences between different muco ciliary systems, within the accuracy of our measurement although relatively large statistical ensembles were used. In addition the wavelength and wave direction of the metachronal wave was examined. All four systems exhibit similar wavelength. The metachronal parameters of muco-ciliary systems exhibit fluctuations (as was demonstrated by the degree of synchronization), however, the magnitude and repetitivity of these fluctuations, is dependent on the loading of the ciliary system. We have loaded the system by increasing the viscosity of the medium. Under viscous load the frequency of the beating decreased. The metachronal wavelength became longer and the metachronal coordination type more orthoplectic. PMID- 2261521 TI - Functional activity of ciliated outgrowths from cultured human nasal and tracheal epithelia. AB - Primary cultures of respiratory epithelium were produced as outgrowths from human fetal and adult tracheal and nasal polyp explants. Video recordings of the epithelial cell outgrowths were carried out after 5 days of culture and the ciliary beating frequency was analyzed by using a video technique. Uniform fields of differentiated ciliated cells were observed near the edge of the explant. In the transition region of the outgrowth from the explant to the outgrowth periphery, isolated ciliated cells were present, as well as cells with fused cilia. The ciliary beating frequency of the outgrowth of well-differentiated ciliated cells (13.5 +/- 1.4 Hz) was significantly higher (p less than 0.001) than the beating frequency of both the explant (11.9 +/- 0.7 Hz) and the ciliated cells with fused cilia (9.8 +/- 1.7 Hz). The same differentiation stages and functional activities were observed in the outgrowth cultures, whatever their origin. These in vitro models are comparable with each other and therefore could be useful for studying the ciliogenesis and functional activity of the human respiratory epithelium. PMID- 2261522 TI - The role of viscosity in oxygen binding to respiratory proteins. AB - Investigations of Myoglobin, Hemoglobin and, more recently of Hemerythrin, suggest that the inward and outward motion of the oxygen ligand is governed by fluctuations between open and closed paths in the protein and that the driving force is the local brownian motion of protein residues. Reaction rates involving protein internal motions are strongly influenced by the viscosity of the solvent, whereas the ultimate binding of oxygen at the protein's active site remains viscosity independent. The description of a protein reaction therefore requires the introduction of a free energy surface with a conformation coordinate accounting for the viscosity-dependent protein transitions in addition to the usual reaction coordinate which only describes the system of reactants in a fixed protein conformation. PMID- 2261524 TI - A new outlook on body fluid viscosity and cell function: concluding remarks and discussion. AB - The area neglected so far in the fields of clinical and theoretical haemorheology is that of interaction between viscosity and chemical reactions in the cells. The reintroduction of teinochemical principle opens entirely new doors for investigation both in vitro and in vivo. Effect of extracellular fluid viscosity on synthesis (i.e. lipids) and on possible enzymatic and catalytic functions influences our opinion that haemorheology has to go back to fundamentals. PMID- 2261523 TI - Solvent viscosity effects on protein dynamics studied by ultrasonic absorption. AB - Solvent viscosity is known to play an important role in the kinetics of biochemical reactions, and has been suggested to modulate the dynamic structure of proteins. The effect of viscous cosolvents, of various molecular sizes, on the apparent ultrasonic absorption of bovine serum albumin in solution, at 37 degrees, has been measured in attempt to investigate the following phenomena: 1) The predicted modulating effect of viscous cosolvents on the "internal friction" of proteins, and 2) Possible differences between the microscopic and macroscopic pictures of the solvent viscosity concerning the proposed effect. We have found that A) The absorption of ultrasound (3-17 MHz) by the protein increases with increasing the cosolvent concentration. B) That increase correlates with the solvent viscosity for small cosolvent molecules, but not with macromolecular cosolvents, and C) Dextran solutions with the same concentration by weight, reveal similar ultrasonic absorption, in spite of large differences in their viscosity. A possible explanation is discussed. PMID- 2261525 TI - The struggle for ignorance about alcohol: American physiologists, Wilbur Olin Atwater, and the Woman's Christian Temperance Union. PMID- 2261526 TI - Water cures and science: the French Academy of Medicine and mineral waters in the nineteenth century. PMID- 2261527 TI - The Pueblo Indian smallpox epidemic in New Mexico, 1898-1899. PMID- 2261528 TI - Hospice to hospital in the Near East: an instance of continuity and change in late antiquity. PMID- 2261529 TI - Can we meet the real need for dialysis and transplantation? PMID- 2261530 TI - The pelvic ileal reservoir: apocalypse later? PMID- 2261531 TI - National cervical screening programme. PMID- 2261532 TI - Screening with discrimination. PMID- 2261533 TI - Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment. AB - OBJECTIVE: To determine the age related incidence of advanced chronic renal failure in two areas of England. DESIGN: Prospective study of patients newly identified as having advanced chronic renal failure within a two year period; subsequent monitoring of patients' clinical course for a further 26 months. SETTING: Devon and Blackburn. SUBJECTS: Those patients in a population of 708,997 who developed advanced chronic renal failure (serum creatinine concentration greater than 500 mumol/l) for the first time during a two year period. MAIN OUTCOME MEASURES AND RESULTS: 210 Patients (148 per million population per year) developed advanced chronic renal failure, 117 (51%) of whom were over 70. The age related incidence rose from 58 per million per year in those aged 20-49 to 588 per million per year in those aged 80 or over. Only 54% (113) of patients were referred to a nephrologist; 120 patients (57%) needed dialysis or died within three months of presenting without receiving dialysis, and 187 (89%) died or needed dialysis within three years. After those unsuitable for further treatment had been excluded, 78 patients per million population per year aged under 80 needed to start long term renal replacement treatment. CONCLUSIONS: Many patients suitable for renal replacement treatment are still not referred for nephrological opinion and are denied treatment. If the treatment rate in the United Kingdom rose from the 1988 rate of 55.1 per million per year to 78 per million per year then the number of patients receiving treatment would rise to about 800 per million. This is double the present number and has considerable but predictable resource implications for the NHS. PMID- 2261534 TI - Prevalence of advanced renal failure in Northern Ireland. AB - OBJECTIVE: To determine the prevalence of advanced chronic renal failure in Northern Ireland as part of an assessment by the Renal Association of the level of service provision for treatment of such patients. DESIGN: Prospective notification of patients reaching a defined level of advanced chronic renal failure (serum creatinine concentration greater than or equal to 500 mumol/l or blood urea concentration greater than or equal to 25 mmol/l) within one year and follow up for at least three, and, at most, four years after notification. SETTING: Northern Ireland. PATIENTS: 122 Patients with a serum creatinine or blood urea concentration higher than the defined level newly detected from 1 March 1985 to 28 February 1986. MAIN OUTCOME MEASURE: Survival after notification. RESULTS: 77 Patients of all ages/million population/year had advanced chronic renal failure compared with 67/million/year between the ages of 5 and 80 found in an earlier study of the same population. 62% Of the patients were older than 50 years. Seventeen (14%) of the patients either required dialysis or died within one month of notification, 51 (42%) survived for at least three months, and 23 (19%) for one year or longer. Three patients, all of whom were attending a renal clinic, survived for periods of 43, 45, and 46 months respectively without renal replacement treatment. CONCLUSIONS: The increased number of new patients disclosed in this survey compared with the earlier survey is mainly owing to an increased number of older patients. Such patients often have disabilities other than renal failure, are less likely to be capable of self treatment, may develop complications more often and require more frequent hospital admissions, and may not be suitable for transplantation and consequently have considerable resource implications for the NHS. PMID- 2261535 TI - Delayed detection of congenital hearing loss in high risk infants. AB - OBJECTIVE: To examine the methods used to investigate children at high risk of congenital hearing impairment, and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified. DESIGN: Clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts. The presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and, whenever possible, a recent pure tone audiogram. SETTING: The United Kingdom. PATIENTS: Children notified to the national congenital rubella surveillance programme and born in 1978-87 in whom IgM specific for rubella was detected shortly after birth. MAIN OUTCOME MEASURES: The age at which hearing loss was identified and the degree of loss in decibels at 250, 500, 1000, 2000, and 4000 Hz measured by pure tone audiometry. RESULTS: 61 (52%) Of 117 children born in 1978-82 had a hearing impairment of 40 dB or greater in both ears. The mean loss was 93 dB. In the following five years 75 (47%) of 159 children had impaired hearing, their mean loss being 96 dB. The age at which the hearing loss was confirmed decreased from 11.6 to 9.8 months as a result of earlier auditory evoked response testing. Nevertheless, only eight (13%) of the children with hearing impairment born in 1978-82 and 16 (21%) of those born in 1983-7 had these tests performed in the first six months of life. CONCLUSIONS: Unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy. Evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss. PMID- 2261536 TI - Catheterisation: your urethra in their hands. PMID- 2261537 TI - Six years' audit of laboratory workload and rates of referral for colposcopy in a cervical screening programme in three districts. AB - OBJECTIVE: To determine laboratory workload and rates of referral for colposcopy in a three district cervical screening programme during 1983-9 to assess the feasibility of accommodating call up of all women at risk, recall at three year intervals (now five year intervals), and investigation of women with all degrees of abnormality. DESIGN: Analysis of computerised screening histories dating back to 1977 of women screened in the Avon cervical screening programme. SETTING: Three district health authorities covering the population of Bristol and Weston super-Mare, comprising 800,000 people, of whom 250,000 were female residents aged 20 to 64. SUBJECTS: 196,977 Women aged 20 to 64 screened in cervical screening programme since 1983. RESULTS: Laboratory workload devoted to follow up of women with abnormalities increased sharply between 1987-8 and 1988-9, with increases of 54% (from 2075 to 3196) in the number of smears for follow up of severe dyskaryosis and invasive cancer, 40% (from 1925 to 2695) for mild and moderate dyskaryosis, and 49% (from 1793 to 2677) for borderline change. The increases were partly explained by the introduction in April 1988 of protocols for follow up and investigation based on guidance in an intercollegiate working party report. The proportion of women with mild and moderate dyskaryosis who were recommended for referral for colposcopy increased steadily from 9.9% in 1983-4 to 79.9% in 1988-9, and for borderline change the proportions were 3.5% and 13.6% respectively. Of all women tested in 1988-9, referral for colposcopy was recommended in 3%. CONCLUSIONS: The increase in laboratory follow up work identified, if it continued, could result in half of existing laboratory capacity in Avon being devoted to follow up work by 1993, with little prospect of maintaining call, recall, and quality control. Investigation of all women with minor cytological abnormalities is neither justifiable nor sustainable and will undermine the benefits of screening by increasing the rate of false positive results and the financial costs. PMID- 2261538 TI - Audit of major colorectal and biliary surgery to reduce rates of wound infection. AB - OBJECTIVE: To reduce the rates of wound infection for major colorectal and biliary surgery. DESIGN: Prospective audit of antibiotic prophylaxis by keeping copies of typed notes of operations and annotating them at discharge and at first follow up visit and annual review of prophylactic regimen according to yearly rate of wound infection and modification if necessary. SETTING: The work of one consultant surgeon working in a district general hospital. PATIENTS: All patients having major colorectal resection during 1976-89 (400) and cholecystectomy during 1981-9 (500). MAIN OUTCOME MEASURES: Wound infection, defined as any discharge from the wound as detected by observation during inpatient stay and by specific questioning at the first follow up visit six weeks later. RESULTS: Serial changes in prophylaxis for colorectal surgery resulted in a progressive reduction in the rate of wound infection from 43% in 1976, with no prophylaxis, to 1% during 1986 9 with single intravenous doses of metronidazole and cefuroxime intraoperatively and with lavage of the peritoneal cavity and wound with 0.1% tetracycline. During 1981-7, with no prophylaxis, the rate of infection in biliary surgery was 12% whereas in 1988-9, after the introduction of lavage with tetracycline alone, the rate was reduced to 2%. IMPLICATIONS AND ACTION: Simple prospective audit identified the need for changes in antibiotic prophylaxis; successive rounds of audit resulted in improved rates of wound infection, and lavage with 0.1% tetracycline seemed to be a major factor in achieving this. PMID- 2261540 TI - Management of major status epilepticus in adults. PMID- 2261539 TI - How district health authorities organise cervical screening. AB - OBJECTIVES: To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered. DESIGN: Postal questionnaire sent to all 190 district health authorities in England in 1989. PARTICIPANTS: 190 District health authorities in England. MAIN OUTCOME MEASURES: Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts. RESULTS: Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed. All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines. At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call. Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results. The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%). CONCLUSIONS: Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer. PMID- 2261541 TI - ABC of major trauma. Major accidents. PMID- 2261542 TI - Availability of condoms in district general hospitals. PMID- 2261543 TI - Lipid screening. PMID- 2261544 TI - Surely a natural cancer remedy can't be dangerous. PMID- 2261545 TI - Resuscitation by ambulance staff. PMID- 2261546 TI - Lowering cholesterol concentrations and mortality. PMID- 2261547 TI - Eye protection in the metal working industry. PMID- 2261548 TI - Importance of ovulation in ovarian cancer. PMID- 2261549 TI - Safety and health in the construction industry. PMID- 2261550 TI - Unexplained haematuria. PMID- 2261551 TI - Selling tobacco to children. PMID- 2261552 TI - Acute intestinal ischaemia. PMID- 2261553 TI - Vitamin A, liver consumption, and risk of birth defects. PMID- 2261554 TI - Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study. AB - OBJECTIVE--To characterise the natural history of sexually transmitted HIV-I infection in homosexual and bisexual men. DESIGN--Cohort study. SETTING--San Francisco municipal sexually transmitted disease clinic. PATIENTS--Cohort included 6705 homosexual and bisexual men originally recruited from 1978 to 1980 for studies of sexually transmitted hepatitis B. This analysis is of 489 cohort members who were either HIV-I seropositive on entry into the cohort (n = 312) or seroconverted during the study period and had less than or equal to 24 months between the dates of their last seronegative and first seropositive specimens (n = 177). A subset of 442 of these men was examined in 1988 or 1989 or had been reported to have developed AIDS. MAIN OUTCOME MEASURES--Development of clinical signs and symptoms of HIV-I infection, including AIDS, AIDS related complex, asymptomatic generalised lymphadenopathy, and no signs or symptoms of infection. MEASUREMENTS AND MAIN RESULTS--Of the 422 men examined in 1988 or 1989 or reported as having AIDS, 341 had been infected from 1977 to 1980; 49% (167) of these men had died of AIDS, 10% (34) were alive with AIDS, 19% (65) had AIDS related complex, 3% (10) had asymptomatic generalised lymphadenopathy, and 19% (34) had no clinical signs or symptoms of HIV-I infection. Cumulative risk of AIDS by duration of HIV-I infection was analysed for all 489 men by the Kaplan Meier method. Of these 489 men, 226 (46%) had been diagnosed as having AIDS. We estimated that 13% of cohort members will have developed AIDS within five years of seroconversion, 51% within 10 years, and 54% within 11.1 years. CONCLUSION- Our analysis confirming the importance of duration of infection to clinical state and the high risk of AIDS after infection underscores the importance of continuing efforts both to prevent transmission of HIV-I and to develop further treatments to slow or stall the progression of HIV-I infection to AIDS. PMID- 2261555 TI - Diagnosis of abdominal masses with percutaneous biopsy guided by ultrasound. AB - OBJECTIVE: To assess the accuracy and safety of percutaneous biopsy of abdominal masses guided by ultrasound. DESIGN: Prospective study. SETTING: Combined gastroenterology service, Scarborough Hospital. PATIENTS: 108 Consecutive patients identified as having a discrete mass on diagnostic ultrasound examination of the abdomen. INTERVENTION: A sample of tissue was obtained with an aseptic technique under local anaesthesia: an 18 steel wire gauge needle (Tru Cut) was mounted in a spring loaded firing device (Biopty gun) that was advanced under simultaneous ultrasound scanning, permitting precise localisation of the target organ. MAIN OUTCOME MEASURE: Results of histological examination of tissue specimens. RESULTS: Biopsy failed in four patients. Adequate histological specimens were obtained in 104 patients with masses in the liver (31), pancreas (37), kidney (10), and adrenal glands (six) and in 20 undiagnosed abdominal and retroperitoneal masses. Follow up was until death or confirmation of the diagnosis. Three complications but no deaths occurred. Malignancy was suspected in 84 patients before biopsy. This was confirmed in 70 patients, in 26 of whom confirmation of dissemination obviated the need for further investigation. In 10 patients biopsy indicated a previously unsuspected primary tumour, and in 12 it showed only a benign lesion. Among 24 patients considered to have benign disease biopsy showed an unsuspected neoplasm in seven. Use of biopsy thus had a major effect on clinical management in 55 patients. Four false negative but no false positive diagnoses resulted from the procedure. CONCLUSION: Percutaneous biopsy of abdominal and retroperitoneal masses under ultrasound guidance is a safe and accurate method of obtaining a histological diagnosis. The results obtained have a considerable effect on clinical management. PMID- 2261556 TI - Junior doctors' on call activities: differences in workload and work patterns among grades. AB - OBJECTIVE: To examine the workload and work patterns of junior doctors of all grades while on call. DESIGN: Pilot study of activity data self recorded by junior doctors, with the help of students during busy periods. SETTING: A general surgical firm and a general medical firm based at University Hospital, Nottingham. SUBJECTS: Four registrars, three senior house officers, and five preregistration house officers. RESULTS: Senior house officers and preregistration house officers spent nearly half of all their on call duty time working, but less than half of that time was spent in direct contact with patients. Registrars were on call more often than the house officers but spent less than one fifth of their on call duty time working, and almost two thirds of that time was spent in direct contact with patients. CONCLUSIONS: Workload while on duty is excessive for both senior and preregistration house officers. Changes in some administrative procedures and employment of more non-medical staff during on call periods might reduce the time spent on non-clinical activities, thereby reducing the overall workload and allowing more time for patient contact. PMID- 2261557 TI - Causes of fatal childhood accidents involving head injury in northern region, 1979-86. AB - OBJECTIVE: To examine the causes and circumstances surrounding fatal accidents involving head injuries in children in the Northern region. DESIGN: Retrospective review of the hospital case notes, necropsy reports, and records of the coroners' inquests. SETTING: Northern Regional Health Authority. PATIENTS: All 255 children aged less than 16 years who died with a head injury during 1979-86. MAIN OUTCOME MEASURES: Cause of injury and circumstances of accident according to reports of inquests; injury severity score; number of fatal accidents and mortality per 100,000 children in 10 groups of local authority wards ranked according to their score on the overall deprivation index; and distance of site of accident from child's home. RESULTS: Of the 255 children who died after a head injury, 136 (53%) children were playing at the time of the accident. 195 (76%) children sustained the head injury in road traffic accidents, 135 as pedestrians, 35 as cyclists, and 25 as passengers in a vehicle. In 120 accidents in child pedestrians the primary cause of accident was the unsafe behaviour of the child. 172 (67%) accidents occurred within one to two km of the child's home and 153 (63%) between 3 pm and 9 pm. The mortality was significantly related to social deprivation; excluding eight children injured while on holiday in the region, 15 fold decrease in mortality was recorded between the local authority wards that ranked highest on the overall deprivation index and those that ranked lowest (14.0/100,000 children, group 10 v 0.9/100,000, group 1 respectively, p less than 0.00001). CONCLUSIONS: The finding that most accidents occurred in children living in deprived areas who were playing unsupervised near their home suggests that childhood mortality might be appreciably reduced if children at play were protected from traffic, particularly in socially deprived areas. PMID- 2261558 TI - Unsuspected renal artery stenosis in peripheral vascular disease. PMID- 2261559 TI - Recording diastolic blood pressure in pregnancy. PMID- 2261560 TI - Tired, weak, or in need of rest: fatigue among general practice attenders. AB - OBJECTIVES: To determine the prevalence and associations of symptoms of fatigue. DESIGN: Questionnaire survey. SETTING: London general practice. PARTICIPANTS: 611 General practice attenders. MAIN OUTCOME MEASURES: Scores on a fatigue questionnaire and reasons given for fatigue. RESULTS: 10.2% Of men (17/167) and 10.6% of women (47/444) had substantial fatigue for one month or more. Age, occupation, and marital status exerted minor effects. Subjects attributed fatigue equally to physical and non-physical causes. Physical ill health, including viral infection, was associated with more severe fatigue. Women rather than men blamed family responsibilities for their fatigue. The profile of persistent fatigue did not differ from that of short duration. Only one person met criteria for the chronic fatigue syndrome. CONCLUSIONS: Fatigue is a common complaint among general practice attenders and can be severe. Patients may attribute this to physical, psychological, and social stress. PMID- 2261561 TI - Brain death and organ donation in a neurosurgical unit: audit of recent practice. AB - OBJECTIVE: To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit. DESIGN: Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989. SETTING: A regional neurosurgical unit serving 2.7 million population. RESULTS: Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed. CONCLUSIONS: More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues. PMID- 2261562 TI - More day surgery. PMID- 2261563 TI - Early diagnosis of acute myocardial infarction. PMID- 2261564 TI - Hirsutism. PMID- 2261565 TI - Catheterisation. PMID- 2261566 TI - Influenza vaccination and the elderly. PMID- 2261567 TI - HIV and surgeons. PMID- 2261568 TI - HIV infection and foreign travel. PMID- 2261569 TI - Interventions in chronic renal failure. PMID- 2261570 TI - Effect of a general practitioner's consulting style. PMID- 2261571 TI - Respiratory distress secondary to naftidrofuryl. PMID- 2261572 TI - Presence of an immunologically-defined class of peri-Golgi vesicles in cultured mammalian cells. AB - Immunsera of mice injected with clathrin-depleted coated vesicle membranes, purified from rat liver, revealed a preferential labeling of some perinuclear structures by immunofluorescence microscopy on NRK cells. Subsequent production of 4 monoclonal antibodies was achieved. The antigen was strictly located in the Golgi area of the cell but was not an intrinsic element of the Golgi complex. The restricted location of the structures excluded these were lysosomes which appeared more dispersed in these cells. After nocodazole treatment the material was found dispersed in the cytoplasm. This provided a means of distinguishing the antigen from clathrin-coated structures and Golgi intrinsic elements. Immunolocalization at the electron microscope level confirmed the data obtained at the light level. Some peroxidase reaction product was rarely associated with Golgi elements, but predominantly stained small neighboring Golgi vesicles (50 nm diameter), as well as tubulo-elongated structures and some large (500 nm) irregular-shaped vesicles. A 32 kDa molecular weight antigen was characterized by immunopurification from NRK cells metabolically labeled with 35S-Met. This 32 kDa antigen appeared as part of a higher multimolecular membrane component of 300 kDa. A 170 kDa and a 70 kDa components were immunodetected in a semi-purified membrane fraction from rat liver, demonstrating that the antigen was a minor but very antigenic contaminant of the coated vesicle preparation used as immunogen. In conclusion, the labeled peri-Golgi structures may be part of the newly characterized trans-Golgi network and/or of the reticular/vesicular endosomal, prelysosomal structure recently described. PMID- 2261573 TI - Effects of cerulenin, an inhibitor of fatty acid synthesis on reconstitution of the dental basement membrane. AB - When trypsin-dissociated enamel organs and dental papillae were recombined in the presence of cerulenin--an antibiotic which is a potent inhibitor of fatty acid synthesis--the newly synthesized basement membrane seemed defective in a dose dependent manner. The three-dimensional relationship between the basement membrane components and the plasma membrane appears to be regulated in part by lipids. PMID- 2261574 TI - Location of Drosophila C virus target organs in Drosophila host population by an immunofluorescence technique. AB - Using the immunofluorescence technique we attempted to locate, in the Drosophila host, Drosophila C virus (DCV) target organs after injection of adult flies. Two kinds of organs were infected: those which play a role in reproductive function, including the fat body and follicular cells, and other, including thoracic muscle fibers, tracheal cells, and the digestive tract. These organs correspond to those found in previous tests. Fat body proteins of a DCV-free host population seemed to cross-react with antivirus C antibody. This immune response depended on the origin of the host population. It is known that, when DCV is ingested from the first larval instar, it may have beneficial effects upon host development and reproduction. As DCV has a narrow host spectrum, it is suggested that it is well adapted to its natural host. Hypotheses are proposed to explain how the host resists viral infection and may in fact benefit from such an infection. PMID- 2261575 TI - Sodium butyrate inhibits c-myc and stimulates c-fos expression in all the steps of the cell-cycle in hepatoma tissue cultured cells. AB - Sodium butyrate decreases the c-myc mRNA and increases the c-fos transcript level in HTC cells. This effect is independent of the cell-cycle phase. Actinomycin D suppresses the effect on c-fos. Cycloheximide increases both mRNA levels. Sodium butyrate suppresses the effect on c-myc and potentializes the effect on c-fos mRNAs. This suggests that sodium butyrate acts at the transcriptional level and that its effect does not result from the arrest of the cells at the G1 phase. PMID- 2261576 TI - Tendon collagen fibrillogenesis is a multistep assembly process as revealed by quick-freezing and freeze-substitution. AB - The ultrastructure of chick embryo tendons has been examined after quick-freezing by liquid helium and freeze-substitution. Several stages of collagen assemblies were observed: intracellular packing of SLS-like aggregates surrounded by membrane containing areas with a clathrin coat; fine non cross-striated filaments connecting the cell membrane at 1 pole of the cells and collagen fibrils; tufts of filaments directly linked to collagen fibrils. This study reveals that some stages are more constant and abundant than supposed (the intracellular SLS-like aggregates) and that other extracellular assemblies that were hypothesized but usually badly preserved by conventional electron microscopy are clearly captured by the method. PMID- 2261577 TI - New cost-cutting strategy impacts CE departments. PMID- 2261578 TI - Technology management in the health care environment--yesterday, today, and tomorrow: Part 2. PMID- 2261579 TI - Disaster planning and the role of the BMET. PMID- 2261580 TI - Establishing the priority of equipment inspections. AB - This article outlines the essential elements of the priority assignment system used by the Clinical Engineering Department at Union Memorial Hospital. By using the department's experience and the professional judgment of its members, choices have been made to discriminate between types of equipment, and so to clearly establish the relative importance of the many different equipment inspections performed by department personnel. Relative priorities have been calculated and communicated to department employees and to others in the hospital who can help the department complete its assigned tasks. Measures have also been developed to show how well the department's actual performance meets its assigned overall objectives. PMID- 2261581 TI - Designing and implementing a performance-based employee evaluation system. PMID- 2261582 TI - A filter device for the prevention of both heparin- and protamine-induced complications associated with extracorporeal therapy. AB - When extracorporeal blood circulation (ECBC) is used, systemic heparinization is necessary to prevent clotting of the blood in the extracorporeal circuit. However, the high circulating heparin concentration needed often leads to bleeding complications. To avoid these, protamine, a heparin antagonist, is administered at the conclusion of the ECBC procedure to reverse the anticoagulant activity of heparin. Intravenous administration of protamine can cause hypotension and shock. To date, there has been no real alternative to control the bleeding risks associated with systemic use of heparin and the adverse effects resulting from heparin reversal with protamine. A novel approach that might control both the heparin- and the protamine-induced complications is suggested. It consists of placing a blood-compatible filter device containing immobilized protamine (a protamine filter) at the distal end of the ECBC apparatus. The filter removes heparin after heparin serves its anticoagulant purpose in the extracorporeal circuit and before blood is returned to the patient. The filter also allows for an external protamine treatment. Since protamine toxicity results from the direct contact of protamine with cells of the liver, lungs, and other organ tissues, the use of an external protamine treatment would minimize it. Protamine was covalently immobilized onto a cellulosic hollow fiber bundle obtained from a clinically used hemodialyzer. The bundle was accessed to the vascular system of a dog by femoral artery and vein cannulation. In in-vivo experiments the protamine-bound fiber bundle not only removed heparin from the extracorporeal circuit, but also caused no clinically significant hemodynamic change in the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261583 TI - NFPA 99 Health Care Facilities--changes and controversy. AB - Overall, the 1990 edition of NFPA 99 represents a refinement of the 1987 edition. Health care professionals need to be aware of several significant changes. PMID- 2261585 TI - Dr. Malcolm Yasny (We should all read his mail!). PMID- 2261584 TI - Fundamentals of diagnostic ultrasonography. AB - Diagnostic ultrasonography uses acoustical waves in the frequency range of 1 to 20 MHz. These waves obey Snell's law of reflection and refraction, which are rules ordinary to wave behavior. In ultrasound, the analogy to momentum is acoustic impedance. The acoustic impedance, Z, is equal to the density, p, times velocity, v. The ultrasound transducer converts electrical energy into ultrasound energy and vice versa. The transducer usually consists of a piezoelectric crystal composed of such ceramic materials as barium titanate, lead titanate, zirconate, or lead metaniobate. Five basic ultrasonic scanning modes play the major roles in clinical applications. A-mode, or amplitude-mode, scanning measures the tissue discontinuity along the scan axis. B-mode scanning produces a two-dimensional image of the tissue under study by combining A-mode signals from various directions through mechanical transducer scanning. M-mode, or time motion scanning, is an extension of the A-mode approach in which a single stationary transducer is used. The depth of the echo is displayed on the vertical axis; the brightness of the oscilloscope display is modulated by the echo amplitude. Real time scanning, or rapid B-scanning, techniques provide continuous data acquisition at a rate sufficient to give the impression of the instantaneous motion of moving structures. Doppler scanning relies on the presence of motion. The Doppler effect occurs when there is relative motion between the source of sound and the receiver of the sound, causing a change in the detected frequency of the sound source. PMID- 2261586 TI - The endo-perio problem in dental practice: diagnosis and prognosis. AB - The relationships between endodontics and periodontics are explored. Diagnosis, prognosis, and treatment planning are discussed for the primary endodontic lesion and the primary endodontic lesion with secondary periodontal involvement. These endodontic lesions are compared with primary periodontal lesions and primary periodontal lesions with secondary endodontic participation. The "true" combined lesion is also reviewed. Clinical photographs and radiographs are used to illustrate specific aspects. PMID- 2261587 TI - Perspectives, controversies and directives on pulpal-periodontal relationships. AB - While established clinical, radiographic and histologic criteria exist to explain the intimate relationship of the pulp and periodontium during pathological states, the recognition, diagnosis and treatment of this perplexing interplay remains a challenge for the practitioner. This dynamic interrelationship is investigated with a focus on simplicity and succinctness to enhance diagnostic probabilities, clarify treatment modalities and provide realistic prognoses in management. PMID- 2261588 TI - New U.S. guidelines for prescribing dental radiographs--a critical review. AB - Most national dental organizations have approved recommendations which set out principles to guide the profession in its use of diagnostic radiation. In 1987, the Center for Device and Radiological Health (an agency of the United States government) published detailed guidelines. This significant initiative should encourage and accelerate the practical application of these principles. In this article, we identify and discuss what we determine to be a major flaw in the guidelines regarding radiography for children in the transitional dentition stage. As well, we have suggested revisions to the guidelines to eliminate some less serious flaws which we believe add unnecessary complexity to the chart. PMID- 2261589 TI - The dental health of 12-year-old children in Dominica: a report of a survey using WHO methods. AB - As part of the process of assisting in the planning of a primary dental health care system in the Commonwealth of Dominica, we conducted a survey of mostly 12 year-old children. The purpose of the survey was to assess the oral health status and identify the needs for treatment and prevention. Secondary purposes included training Dominican dental auxiliaries and assistants to collect epidemiologic data and to use the findings to compare oral health status by region and previous coverage by the auxiliaries. The sample was obtained from schools throughout the country. Examinations were conducted according to standard WHO methods, using mirrors and explorers. The findings were recorded on prepared forms and the data were processed in Toronto using microcomputers. We found 31% of children to be caries-free and the mean DMFT score to be 2.5 (95% CI 2.2-2.7). Only 8% of lesions had been treated. No differences were observed by region but in areas covered by dental auxiliaries, children had fewer decayed teeth, fewer DMFT and higher F/DMFT ratios. Only 17% scored 0 on the CPITN index and 63% scored 2, meaning they had calculus. Debris was 3.6 times more likely to be found among those with gingival bleeding or calculus compared to those with periodontal health. Single surface restorations made up 82% of the estimated 2.0 caries treatment services required. The survey findings will allow planners to design specific preventive and treatment programs to meet Dominica's needs. PMID- 2261590 TI - Chairside repair of ceramo-metallic restorations. AB - The ceramo-metallic crown has enjoyed increasing universal popularity as the full coverage restoration of choice where long-term esthetics is desirable. The porcelain veneer is colour stable and relatively wear resistant. It has excellent compressive strength but poor tensile and shear strength, which unfortunately can result in fracture. Consequently, there is a need for chairside repair, since remake is often contraindicated. Commercially available repair systems are inconsistent and unpredictable and provide, at best, only temporary results despite recent improvements in materials and technique. Two new adhesive composite resins appear promising, although long-term clinical studies are not available. This article deals first with prevention and a review of the literature. Secondly, clinically proven methods of providing mechanical retention for resin and composite resin repairs of fractured porcelain are presented. The combination of mechanical retention and recently developed adhesive composite resins should provide the dentist with a reliable chairside repair system that could last for many years. PMID- 2261591 TI - [Treatment of dentin hypersensitivity: a retrospective and comparative study of two therapeutic approaches]. AB - Stimulation on exposed dentine at the enamo-dentinal junction is often painful and uncomfortable for the affected patient. Two hundred and forty-four subjects suffering from dentinal sensitivity, aged from 18 to 48 years old, were treated with two types of desensitizing agent. In this study, we used sodium fluoride (Duraflor) and calcium hydroxide (Dycal catalyst). The desensitizing agent is first applied on the exposed dentine and then burnished, without local anaesthesia, until all sensitivity has disappeared. After the first session, 100% of the subjects were desensitized. All subjects were seen 1, 2, 3, 6, 13 and 26 weeks after the first application. After 6 months, 94% of the subjects treated with calcium hydroxide (Dycal) and 87% of those treated with sodium fluoride (Duraflor) were still desensitized. This difference is statistically significant at alpha = 0.01 (Anova test). In conclusion, our study reveals that both calcium hydroxide (Dycal) and sodium fluoride (Duraflor) are effective in the treatment of dentinal hypersensitivity. A slight significant advantage in using calcium hydroxide is also noted. PMID- 2261592 TI - Statistics cause static. PMID- 2261593 TI - Implants: not enough evidence. PMID- 2261594 TI - The Soft Gingival Model. PMID- 2261595 TI - Let your voice do the charting. PMID- 2261596 TI - Carbohydrate-derivatized immunoconjugate of the anti-(carcinoembryonic antigen) monoclonal antibody C46: immunohistological reactivity and pharmacokinetic comparison with a randomly derivatized C46 immunoconjugate. AB - In this study, a site-specific glycyl-tyrosyl-(N-epsilon diethylenetriaminepentaacetic acid)-lysine (GYK-DTPA) immunoconjugate of the anti carcinoembryonic antigen monoclonal antibody C46 (C46-GYK-DTPA) was characterized by immunohistological and immunofluorescence methods for reactivity with normal and neoplastic human tissues. In addition, pharmacokinetic studies assessed the ability of C46-GYK-DTPA labeled with 111In to localize to and image human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues. C46 did not bind to the surface of normal human granulocytes, which indicates lack of reactivity with normal cross-reacting antigen. C46-GYK-DTPA reacted with 100% of the colon, breast and renal carcinomas examined and with two of three lung carcinomas, but did not react with any sarcomas, melanomas or lymphomas examined. Intravenously administered C46-GYK-DTPA-111In rapidly localized to and imaged LS174T human colon adenocarcinoma xenografts in nude mice, reaching maximal levels of about 25% of injected dose/g tumor within 1 day. No unusual localization to any non-tumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that in the blood. The accessible binding sites in 1 g tumors appeared to be saturated at an antibody dose between 100 micrograms and 1000 micrograms/mouse. Further, in a direct in vivo comparison, the site-specific conjugate C46-GYK-DTPA had more favorable pharmacokinetics and better tumor localization than a randomly derivatized C46 immunoconjugate (C46-DTPA). These findings suggest that the site specific immunoconjugate C46-GYK-DTPA may be useful in the diagnosis and therapy of colon cancer and other adenocarcinomas expressing carcinoembryonic antigen. PMID- 2261597 TI - The influence of anti-(ricin toxin A chain) monoclonal antibodies on the pharmacokinetics of ricin toxin A chain and recombinant ricin A chain in mice. AB - Two monoclonal antibodies against ricin toxin A chain (RTA) have been examined for their effects on the blood survival and biodistribution of RTA and recombinant ricin A chain in mice. When admixed with the toxins at 1:1 molar ratios prior to intravenous injection, the antibodies prolonged blood survival and whole-body retention of both species of RTA, and this was due essentially to reduced renal clearance of the toxins. Immune complexes were identified by gel filtration chromatography and immune precipitation with anti-IgG antiserum in mixtures prior to injection and in the serum of mice injected with the mixtures. An irrelevant monoclonal antibody showed no complex formation, and no effect on biodistribution. These studies have shown that immune complexes formed between monoclonal antibodies and protein antigens of molecular mass up to at least 30 kDa survive in the circulation, rather than being cleared by the reticuloendothelial system. Such antibodies could be used to modulate the biodistribution of toxic molecules such as ribosome-inhibiting proteins like RTA. This might be exploited therapeutically, for example in the construction of bispecific antibodies against ribosomal inhibiting proteins and tumour-associated antigens. PMID- 2261598 TI - Flavone acetic acid antitumour activity against a mouse pancreatic adenocarcinoma is mediated by natural killer cells. AB - Flavone acetic acid (FAA) is one of the most active antitumour agents against mouse solid tumours. A number of reports favour the hypothesis that FAA could behave as a biological response modifier; in fact FAA stimulates natural killer (NK) cells, induces secretion of type I interferon and synergizes with interleukin-2 to increase NK/lymphokine-activated killer (LAK) activity in vivo. However, there is no conclusive evidence that the antitumour activity of FAA is mediated via the modulation of NK/LAK cells. The present study was designed to evaluate whether the reported activation of NK cells is instrumental in FAA antitumour activity. FAA (180 mg/kg, i.v. on days 3, 7 and 11 after tumour implant) was significantly effective in inhibiting the subcutaneous growth of the pancreatic adenocarcinoma PAN/03 in C57/Bl mice. After 132 days the number of tumour-free survivors was 36%, whereas in the control group receiving no treatment, or in the group of mice treated with 10 micrograms/mouse of alpha asialo-GM1 the value was only 0 or 6.7%, respectively. The combination of FAA and alpha-asialo-GM1 resulted in only 6% tumour-free mice. In parallel experiments, splenocytes and peritoneal cells from C57/B1 mice were tested in a standard cytotoxicity NK assay. While animals treated with FAA showed a significant increase in NK activity, those injected with alpha-asialo-GM1 had very low levels, and the combined treatment of FAA and alpha-asialo-GM1 resulted in a lower or similar NK activity compared to that in untreated mice. The fact that the abrogation of the NK-stimulating effect of FAA is accompanied by a lack of anti-tumour activity indicates that, at least in this experimental model, FAA is likely to act via an immunomodulatory mechanism. PMID- 2261599 TI - The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor alpha. AB - Pyrimidinones, like 2-amino-5-bromo-6-phenyl-4-pyrimidinone (bropirimine), are potent immunomodulators. Natural killer cell activity and macrophage cytotoxicity are increased after bropirimine treatment, an effect exerted through induction of cytokines. Up to now, the interferons have been supposed to be the main mediators but we have found that tumour necrosis factor alpha (TNF alpha) can also be an important mediator of the bropirimine antitumour effects. Increased serum levels of TNF alpha were seen in rats after intraperitoneal administration of 200 mg/kg bropirimine on 2 consecutive days. We also found that the tumour-growth inhibiting effect of the drug on a colon carcinoma in rats could be reduced about 40% by giving the rats rabbit anti-TNF alpha serum just prior to drug treatment. These results indicate that bropirimine can induce the release of TNF alpha in vivo and that this endogenous TNF alpha may be important as far as the antitumour effect of the drug is concerned. PMID- 2261600 TI - Intrinsic B lymphocyte defect in untreated patients with Hodgkin's disease. AB - In vivo and in vitro humoral and cell-mediated immunological defects have been described in untreated patients with Hodgkin's disease (HD). The cellular basis of the recently described in vitro reduction of mitogen-induced immunoglobulin synthesis has not been elucidated so far. In this study, we attempted to dissect T and B lymphocyte function in untreated HD patients. Mitogen-induced in vitro immunoglobulin synthesis was assessed in the presence of pokeweed mitogen, the mitogenic anti-CD3 monoclonal antibody OKT3 and the relatively T-cell-independent B cell mitogen Nocardia opaca delipidated mitogen (NDCM). Mitogen-induced Ig synthesis by HD peripheral blood mononuclear cells was significantly reduced compared to that in control peripheral blood mononuclear cells. In coculture assays, T cells of HD patients exerted an adequate helper function to control B cells. However, normal donor T cells did not restore Ig synthesis by B cells of HD patients. Finally, B cells of HD patients were unresponsive to NDCM, which is able to induce Ig synthesis in control B cells even in the absence of T cells. These data provide evidence for an intrinsic functional B lymphocyte defect in HD patients, and suggest that increased activation of suppressor HD T lymphocytes may not play a significant role in the suppression of in vitro Ig synthesis. PMID- 2261601 TI - Fluoride penetration into dentine abutments in vitro. AB - The diffusion of fluoride ions from various concentrations of sodium fluoride solution into the dentine of decoronated human canine teeth, prepared as for reception of overdentures, was studied in vitro. The decoronated preparations were immersed for 7 days in 2.0, 1.5, 1.0, 0.5 and 0.05% solutions of neutral-pH sodium fluoride and then fluoride penetration into the prepared transverse face of the dentine was assessed by electron microprobe. Only with high concentrations of fluoride (2.0%) was there significant penetration. In peritubular dentine, fluoride penetration could be measured to a depth of 400 microns, but in intertubular dentine penetration did not take place beyond 100 microns. These findings call into question the efficacy of patient-administered caries prophylaxis with low-concentration fluoride treatments in overdenture cases. PMID- 2261602 TI - Interactions of selenium and fluoride on growth, glycolysis and survival of Streptococcus mutans GS-5. AB - The effects of low concentrations (1.0 mmol/l of selenite and seleno-dl-cystine were tested alone, or in combination with NaF, on growth, glycolysis, and survival of Streptococcus mutans GS-5. In batch culture, both selenium-containing compounds (1.0 mmol/l) inhibited the growth rate and final cell yield by 92% or greater; glycolysis, however, was not affected. The observed bactericidal action of selenite at 0.1 mmol/l was pH-dependent. Fluoride reduced the killing effect of SeO3 in the culture medium and in a lactate-acetate buffer system at pH 6.5, 5.0 and 4.0. These data indicate that selenium-containing compounds exert an antibacterial action on cells of S. mutans in a manner which leaves glycolysis unaffected. PMID- 2261603 TI - Correlations between numbers of microflora in plaque and saliva. AB - An epidemiologic investigation to reliably identify caries-susceptible subjects by microbiological and chemical assessment of plaque and saliva is currently in progress. As part of that study, the numerical relationships of mutans streptococci, lactobacilli and total viable microflora in plaque and saliva among 12- to 15-year-old children in a fluoridated community were determined. Paraffin stimulated whole saliva and pooled dental plaque were collected. Each sample was suspended in reduced transport fluid, chilled on ice, and assayed. The bivariate normal distribution was found to be a suitable model for the distribution of the pairs [numbers of bacteria in plaque (log10), numbers of bacteria in saliva (log10)]. Statistically significant positive correlations were found between numbers of mutans streptococci in plaque and saliva, and between lactobacilli in plaque and saliva. PMID- 2261604 TI - Depth of occlusal caries assessed clinically, by conventional film radiographs, and by digitized, processed radiographs. AB - Occlusal caries depth was assessed in 47 extracted premolars and permanent molars by 4 observers on a rank scale by eye inspection, by film radiographs, and by 2 of the observers also by digitized radiographs after filtering and contrast enhancement of the image. Quantitative estimates of caries depth were obtained from the digitized radiographs. Accuracy of scorings was determined with the histologic section as validating criterion. Occlusal caries was present in a spectrum from incipient fissure decalcification to large cavity formation. Clinical as well as radiographic scorings most frequently under-estimated lesion depth. Accuracy of radiographic assessments increased substantially by digital processing of the radiographic image. Quantitative measures of caries depth on digitized radiographs were strongly correlated to the histologic measures (r = 0.91). Interobserver agreement was fair to moderate according to kappa coefficients for the clinical and the radiographic scorings. The agreement was highest for the scorings of the digitally enhanced images. The study suggests that digital processing of radiographic images constitutes a diagnostic aid that may give a more accurate estimate of occlusal caries depth. PMID- 2261605 TI - Effect of fruit juice, with or without 1% added whey mineral, on bovine dental enamel in intraoral experiments. PMID- 2261606 TI - Cariogenic potential of foods. I. Caries in the rat model. AB - As part of a major study to identify cariogenic elements of foods, the cariogenic potential of 22 foods relative to sucrose (confectioners' sugar) was determined over six intubation rat caries experiments. Cariogenic potential indices were calculated for each food from sulcal and buccal-lingual caries based on both number and severity. Those foods with the lowest cariogenic potential indices were peanuts, gelatin dessert, corn chips, yoghurt, and bologna; with the highest cariogenic potential indices were sucrose, granola cereal, french fries, bananas, cupcakes, and raisins. There was no simple relationship between food sucrose content and caries. Enhanced cariogenic potential was associated with foods containing approximately 1% or more hydrolyzable starch in combination with sucrose or other sugars. PMID- 2261607 TI - Fluoride administration during enamel formation and its effect on dental caries in rats. PMID- 2261608 TI - Variability in the ingestion of toothpaste by preschool children. AB - The amount of dentifrice used and ingested on three occasions by a group of 48 children aged between 3 and 5 years was measured. The purpose of the present study was to investigate the variability in the amount of dentifrice used and ingested. The quantity of toothpaste ingested was derived from the differences between the amounts used and rejected. On average, the difference in the amount used between any two brushings was less than 0.250 g for 66% of the subjects, and the difference in the amount ingested was less than 0.100 g for 69% of the children. There were no statistically significant differences in the quantities used and ingested between the three brushings. PMID- 2261609 TI - Radiographic versus clinical diagnosis of approximal carious lesions. AB - For school-age children, in whom caries activity has declined considerably, the efficiency of bitewing radiographs in diagnosing approximal lesions requires reevaluation. Therefore parallel clinical and radiographic examination of approximal surfaces were carried out in 317 14-year-old children. To assess the degree of agreement between both methods sensitivity and negative predictive value were determined. At the same time previously published data of children aged 8 through 12 years were reassessed. From the results it is concluded that omission of radiographic examination will not result in a substantial loss of information under the age of 12, but above this age it is advisable to include radiographic diagnosis for approximal surfaces. PMID- 2261610 TI - Caries control in overdenture patients: 18-month evaluation on fluoride and chlorhexidine therapies. AB - The aim of this study was to test the clinical effects of preventive regimens using fluoride and chlorhexidine on caries development in abutment teeth in patients with overdentures. 30 patients with immediate overdentures were distributed at random among three experimental groups. In these groups three different gels (placebo, fluoride, and chlorhexidine-fluoride) were tested by daily application. The patients were recalled at 6-month intervals for a period of 18 months. The life table survival ratios at patient level showed that in the chlorhexidine group caries development in the abutments was significantly reduced. In this group no caries developed. On comparison with the control group (placebo), no preventive effects of the gel were noticed for those in the fluoride group. PMID- 2261611 TI - Influence of calcium lactate rinses on calculus formation in adults. PMID- 2261612 TI - [Epidemiologic surveillance of pneumonia among children in the MCH model counties in 1986]. AB - Epidemiologic study of children pneumonia was carried out by the Capital Institute of Pediatrics in collaboration with six medical schools in six MCH Model Counties. Data indicated that pneumonia was not only the No. 1 cause of death in order among infants and children in community but also in hospitals, and the No.1 disease of children for hospitalization. The average morbidity of pneumonia in infants in study areas was 158.46 per 1000. The average mortality of pneumonia was 740.18 per hundred thousand. Both the incidence and the case fatality rate were the highest in infants. The incidence was still high in 1-2 year old group, but the case fatality rate became lower. Both the incidence and the case fatality rate were the lowest in 3-14-year old group. 92.45% of fatal cases of pneumonia were infant. PMID- 2261613 TI - [A prospective serological epidemiological investigation of hepatitis B virus infection in a prison]. AB - 2,443 male prisoners were under investigation, most of them were youth, and followed up for 12-36 (mean 23.7 +/- 11.4) months. Sera HBV markers were detected every year. The positive rate of HBsAg was 25.1%, in which transient HBV carriers were 14.7% and chronic asymptomatic HBV carriers (AsC) were 85.3%. Seroconversion rate of HBsAg in AsC was 1.4% per year. The positive rate of anti-HBs was 46.3%, anti-HBs diminished in 6.0% per year. It was suggested that the antibody response to frequent exposure to HBV persisted for a long time. HBeAg seroconversion was 22.3% per year, and its reoccurrence was 7.9% per year, indicating the fluctuation and stability of infection status. The prevalence rate of HBV infection (with one or more than one of HBsAg, anti-HBs or anti-HBc) was 81.1%. Incidence of HBV infection among those susceptible persons found at first investigation was 22.3% per year. PMID- 2261614 TI - [An experimental study on preparing monoclonal antibodies of rough Brucella spp. and identification species Brucella]. AB - A report of preparation of monoclonal antibodies of B. canis and B. ovis and the use of identification for rough species of Brucella was described. The results showed that the above two monoclonal antibodies were specific for rough Brucella Spp. The use of the above described monoclonal antibodies gave us the possibility to differentiate rough and smooth Brucella species. The results also showed that the ELISA using monoclonal antibodies of rough Brucella Spp. was more specific than the agglutination test using routine antibodies of rough Brucella. PMID- 2261615 TI - [A preliminary investigation of an outbreak of Legionnaires' disease caused by Legionella micdadei at a building-site in the rural area of Beijing]. AB - During the period from December 1989 to January 1990, An outbreak of upper respiratory infection (influenza-like syndrome) took place in the workers of a building-site in a rural area of Beijing. An epidemiological investigation and bacteriological examination were carried out in this area. The results showed that it was an outbreak of Legionnaires' Disease caused by Legionella micdadei (Lm). The incidence was 26.67% (24/90). This was the first report on Lm infection in China. PMID- 2261616 TI - [An epidemiological investigation of an outbreak of Legionnaires' disease in a college in Tang Shan]. AB - An outbreak of Legionnaires' Disease (LD) in a college in Tang Shan in the winter of 1987 was reported. Indirect fluorescent assay (IFA) for the antibodies against Legionella Pneumophila (Lp) serogroups I, VI and VIII was carried out in 52 students and 6 teachers. It was found that the antibody titer of LP VI greater than or equal to 1:256 was in 12 students. The clinical figures of these patients were classified into three types: pneumonia 3, fever 9 and asymptomatic 1. It was postulated that the outbreak was associated with water contamination of the college bathroom. There were more patients in two dormitories than in the others, which was suggested that the possibility of a spread of the disease from a person to the others. PMID- 2261617 TI - [A survey of nosocomial infection by Salmonella typhimurium]. AB - 140 cases of infections by Salmonella typhimurium were studied from June 1987 to the end of 1988. Among those patients 56% of the cases were hospital-acquired. The nosocomial infection rate of the disease in the hospital was 14.6%. The majority of these cases were found in infants and young children. The sources of infections were the sporadic out patients. Improper isolation and disinfection caused the spreading of the infection in the hospital. As we noticed, nosocomial infection by S. typhimurium could occur during the whole year and had an increased incidence in winter. Due to pathogens isolated from those patients were highly resistant to antibiotics so the nosocomial infection could delay the hospitalization time, therefore how to control it became an important aspect of the hospital. PMID- 2261618 TI - [An investigation on injectional gluteal muscle contracture in childhood in Mianyang City]. AB - An investigation of 9845 healthy children with age of 3-12 years in Mianyang urban area has been made by us. One hundred and twenty-two cases of injectional gluteal muscle contracture were diagnosed. The morbidity is 1.36% and it is more common in boys than in girls (OR: 3.71). The prevalence rate of the age group from 4 to 7 is highest and it decreases markedly with aging. This is probably due to self-recovery of some mild cases. Repeating injections of diluted penicillin by 1.5-2% Benzyl alcohol are the predominant causative factor of the disease. If Benzyl alcohol as a solvent for penicillin in children was no longer using, it would possibly reduce the morbidity. Up to now, this is a common iatrogenic disease in pediatric population and special attention should be paid to it. PMID- 2261619 TI - [A case-control study of risk factors of colorectal cancer in Shanxi Province]. AB - A case-control study of risk factors of colorectal cancer was conducted in 202 cases and 404 controls. The results of conditional logistic regression analysis showed that the history of intestinal diseases, psychic trauma, eating of more protein and fat, unhealthy eating habit, deficiency of fruits were risk factors of colorectal cancer; and the odds ratio were 2.86, 8.67, 1.64, 2.70, 1.48 respectively. Blood selenium levels were determined by fluorometric method. Significantly lower selenium values were observed in blood from colorectal cancer patients than from normal individuals (0.1349 ppm vs. 0.1502 ppm. P less than 0.01). PMID- 2261620 TI - [Investigation on the distribution and serotyping of V. parahaemolyticus isolated from marine products and environment in Zhoushan archipelago]. AB - Isolation for V. parahaemolyticus from 1003 samples of marine products and environment was attempted in Zhoushan archipelago in 1986-1987. The results showed that V. parahaemolyticus could be detected from all kinds of marine products, the positive rate was between 40%-100%. The V. parahaemolyticus was detected in all samples from the environment. The main O groups were O2, O5, O1, O4, O3 and O12, the O9 groups was not detected. Although 103 serotypes have been detected, the main serotypes were O1K32, O5K17, O5K15, O2K28, O2K3 and O12K51(52), 17.9% of the strains could not be typed. PMID- 2261621 TI - [Epidemiological survey of endemic fluorosis in Xiou Shan and Bao Jing areas]. AB - It may be affirmed that Mushan in Bao Jing county is a light fluorosis area and Yan Tian in Xiou Shan county is a middle fluorosis area with the help of following investigations: fluoride levels in inhalatable dust, food, drinking water, soil, coal, biological effects of fluoride on habitants and the burden of fluoride in the body of habitants. It is demonstrated that the cause of fluorosis is above areas is essentially the oral intake of excess fluoride through the foods, mainly maize, polluted by burning coal fly ash containing fluoride. PMID- 2261622 TI - [Advances in the disinfection of water distribution systems for Legionella]. PMID- 2261624 TI - Food consumption patterns of the people in the Mutambara District of Zimbabwe. PMID- 2261623 TI - Clinical presentation of symptomatic human immuno-deficiency virus in children. PMID- 2261625 TI - Determinants of obstetric outcomes: a study of primiparae in central Saudi Arabia. AB - In a prospective study, 200 consecutive Saudi patients having their first labour and delivery were compared with 80 non-Saudi primiparae. The duration of labour and mode of delivery were similar in both groups, but the Saudis were younger, required less sedation, and had lighter babies. The perinatal mortality rate was 10 per 10,000 in the Saudis and 25 per 1,000 in the non-Saudis. Anxiety played a more significant role in the labour and delivery of the foreigners. Lifestyles rather than racial or ethnic differences may explain differences in obstetric outcomes between different populations. PMID- 2261626 TI - Usefulness of the bleeding time to predict the risk of clinical bleeding in patients with uraemia. AB - In a prospective study of haemostatic status of 15 uraemic Nigerians a highly significant prolongation of bleeding time (p less than 0.001) and significantly lower haematocrit levels (p less than 0.001) were detected in comparison to healthy controls. A highly significant positive correlation (r = +0.778) between prolongation of bleeding time and blood urea was present. Six patients had overt clinical bleeding with significantly prolonged bleeding time (p less than 0.01) compared to uraemics without overt bleeding. Blood urea was significantly different in both groups (p greater than 0.1). Platelet count, prothrombin time, partial thromboplastin time and Hess tourniquet test did not differ between the uraemic patients and controls. Haemostatic dysfunction has been noted in Nigerian uraemics we studied. Bleeding time is a useful but simple means of assessing such dysfunction. PMID- 2261627 TI - Atmospheric pollution in hospitals, medical and scientific laboratories: a brief review. AB - The common causes of activity-related atmospheric pollution in hospitals, medical and scientific laboratories with their associated health problems are briefly surveyed. Recommendations and current developments for the control of this problem in the work-place are discussed in broad outline. PMID- 2261628 TI - Neuroleptic malignant syndrome. AB - While on holiday in Zimbabwe, a forty-one year old woman with a long history of intermittent psychiatric illness developed what was diagnosed as neuroleptic malignant syndrome. She was admitted to the Intensive Care Unit of Harare Central Hospital and was treated successfully with bromocriptine and dantrolene. PMID- 2261629 TI - Zimbabwean birthweight for gestation standards. AB - Birthweight for gestation standards were derived in a study of 5,872 women with ascertainable menstrual dates in Harare, Zimbabwe. The smoothed 5th, 50th and 95th centiles of birthweight for gestation were described for 24 to 42 weeks and these fitted linear quadratic functions. Male infants were significantly heavier than females from 36 weeks onwards and parity differences appeared at 38 weeks gestation. The results suggest that in this population, low birthweight should be defined as 2,000gm or less, rather than a birthweight of less than 2,500gm. PMID- 2261630 TI - Air-conditioning and health: effect on pulse and blood pressure of young healthy Nigerians. AB - Blood pressure and pulse of 32 young healthy Nigerian volunteers were determined after they had been in an air-conditioned room from between 60 and 90 minutes. The same determinations were made at the same time of another day with air conditioning switched off for the same period. The mean systolic blood pressure (SBP) was 115.3 +/- 11.5 mmHg under air-conditioner (AC) and 108.5 +/- 10.1 mmHg without air-conditioning. This difference was statistically significant (p less than 001). Similarly, diastolic blood pressure (DBP) was higher in AC, 69.4 +/- 8.9 mmHg, than without AC, 66.5 +/- 9.1 mmHg (p less than 025), while mean blood pressure was also higher in AC, 84.9 +/- 9.1 mmHg, than without, 79.9 +/- 7.7 mmHg (less than 005). There was no significant different in pulse rate. These differences in the BP of normal young subjects are not thought to be of clinical significance but the result suggests that study of the effect of AC on BP and pulse in older subjects and hypertensive subjects is desirable. PMID- 2261631 TI - Neonatal septicaemia in Harare Hospital: aetiology and risk factors. The Puerperal Sepsis Study Group. AB - During February to June 1987, one hundred and sixty one babies admitted to Harare Neonatal Unit had positive blood cultures, giving a sepsis rate of 21/100 live births at Harare Hospital. The case records of these 161 babies were reviewed and compared with records of 50 babies admitted from the same catchment area and during the same time period but who had negative blood cultures. Babies with early (less than 48 hr) onset or late onset sepsis tended to have lower birth weights and shorter gestational ages than controls. Significant risk factors in maternal history were poor antenatal care and prolonged rupture of membranes. Hypothermia, respiratory distress, jaundice and hypoglycaemia were all common findings in babies with sepsis. Staph. aureus and Group B streptococci (GBS) were the most common isolates in both early and late onset sepsis, with Esch. coli and Klebsiella sp. being more common in early than in late onset disease. Cultures from the genital tract were obtained from 28 of the mothers whose babies developed sepsis. Only rarely, however, was an organism with similar identity and antibiogram to that isolated from the blood culture of the baby obtained from the mother. Nevertheless mothers of blood culture positive babies showed high carriage rates of GBS, B. melaninogenicus and Klebsiella. The overall mortality in sepsis cases was 28.5 pc, but mortality was discouragingly high where coliforms or Staph.epidermidis were isolated. PMID- 2261632 TI - Solitary symptomatic non-parasitic cyst of liver presenting as pancreatic pseudocyst. AB - A case of a solitary symptomatic non-parasitic cyst of the liver, was seen and treated at the Muhimbili Medical Centre, Dar Es Salaam. This is the first case report from Tanzania, cystic disease of the liver is rarely diagnosed clinically, the possibility should be seriously considered in any patient with an enlarged liver which is associated with few or no symptoms and little or no impairment of liver function. In African countries, it is suggested that non-parasitic cysts of the liver be considered in the differential diagnosis of hepatocellular carcinoma because of its high prevalence rate in these countries. PMID- 2261633 TI - MEDLINE on-line: an information service on CD-ROM. PMID- 2261634 TI - Cell fates in C. elegans: in medias ras. PMID- 2261635 TI - FAR-reaching discoveries about the regulation of START. PMID- 2261636 TI - Control of plasmid replication--how do DNA iterons set the replication frequency? PMID- 2261637 TI - Molecular cloning and expression of an IL-6 signal transducer, gp130. AB - Interleukin-6 (IL-6) signal is transduced through a membrane glycoprotein, gp130, which associates with IL-6 receptor (IL-6-R). A cDNA encoding human gp130 has been cloned, revealing that it consists of 918 amino acids with a single transmembrane domain. The extracellular region comprises six units of a fibronectin type III module, and part of this region of approximately 200 amino acids has features typical of a cytokine receptor family. A cDNA-expressed gp130 showed no binding property to IL-6 or several other cytokines. Although a transfectant with an IL-6-R cDNA expressed mainly low affinity IL-6 binding sites, an increase in high affinity binding sites was observed after cotransfection with a gp130 cDNA. This confirmed that a gp130 is involved in the formation of high affinity IL-6 binding sites. A cloned gp130 could associate with a complex of IL-6 and soluble IL-6-R and transduce the growth signal when expressed in a murine IL-3-dependent cell line. PMID- 2261638 TI - The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor. AB - The Drosophila ncd gene is required for chromosome segregation during female meiosis. Previous analyses suggested that the ncd gene encoded a protein with sequence similarity to the kinesin motor domain, which suggested that, like kinesin, the ncd protein might be a plus end-directed microtubule motor. Here we describe the expression of ncd protein in E. coli and the initial characterization of the ncd protein's motor properties. The ncd protein is indeed a microtubule motor, but the polarity of movement is minus end directed. The ncd protein also has microtubule bundling activity. These findings limit possible models for the in vivo functions of the ncd protein and suggest that motor proteins with similar sequence can generate movement in opposite directions along a microtubule. PMID- 2261639 TI - The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. AB - The Drosophila segment polarity gene armadillo is required for pattern formation within embryonic segments and imaginal discs. We have found that armadillo is highly conserved during evolution; it is 63% identical to human plakoglobin, a protein found in adhesive junctions joining epithelial and other cells. We have examined arm protein localization in a number of larval tissues and found that arm protein accumulation within cells shares many features with the accumulation of plakoglobin. We have compared the phenotype and molecular lesions responsible for the different arm mutations. Surprisingly, severely truncated proteins retain some function; the degree of function is strictly correlated with the length of the truncated protein, suggesting that the internally repetitive arm protein is modular in function. We present a possible model for the cellular role of arm. PMID- 2261640 TI - The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans. AB - The tra-1 gene plays a central role in C. elegans sex determination. XX animals develop as hermaphrodites when tra-1 is active and as males when it is not. By analyzing a large number of tra-1 genetic mosaics we have shown that, with the expected exception of vulval induction by the hermaphrodite gonad, tra-1 functions cell-autonomously, consistent with a role as an intracellular component of a signaling pathway. Moreover, all the sexual differentiation genes under tra 1 control must also function cell-autonomously. Our results have additional implications for several aspects of postembryonic development, including mechanisms of sex-specific directed cell migrations and the question of an organizer in the male tail. PMID- 2261641 TI - Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. AB - Transient transfection into L8 myoblasts has been used to study the rat alpha actin gene promoter. Demodification of specific sites occurs in two stages, with a hemimethylated intermediate formed within a few hours after entry of the alpha actin gene construct into the cell. The removal of the methyl moiety from the complementary strand takes place after a delay of at least 48 hr, and both events are actively carried out in the absence of DNA replication. By assaying gene activity during the course of the transfection, it was possible to demonstrate that demethylation of both strands at the critical CpG loci is essential to activate transcription. Genetic analysis revealed the existence of cis-acting elements required for demethylation. The recognition of these sites early in the differentiation process probably leads to the demodification events required to make the gene accessible to its transcription factors. PMID- 2261642 TI - Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies. AB - Muscle dystrophin mRNAs from Duchenne (DMD) and Becker (BMD) patients with internal deletion of the DMD gene were quantitated and sequenced. In all cases (eight DMD and three BMD), truncated mature transcripts were found, and their amount was correlated to the clinical phenotype and to the reading frame. We focused on four cases that were apparently not in agreement with the reading frame rule. In two DMD cases, slightly reduced amounts of in-frame truncated mRNA are present but no dystrophin is detected, suggesting impaired translation and/or instability of the protein. In two BMD patients with out-of-frame deletions, the presence of minor in-frame alternatively spliced mRNA species is congruent with the observed truncated dystrophin and the mild phenotype. PMID- 2261643 TI - Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. AB - The liver-enriched transcriptional activator protein DBP accumulates in hepatocytes of adult rats according to a strictly controlled circadian rhythm. DBP is not detectable in liver nuclei during the morning hours. Its level raises sharply during the afternoon and reaches a maximum at about 8 p.m. During the night the cellular DBP concentration decreases below detectability. This oscillation is "free running," transcriptionally regulated, and may be under the negative control of glucocorticoid hormones. In keeping with the rhythmicity of DBP accumulation, the albumin gene, a putative target of DBP, is transcribed more efficiently in the evening than in the morning. PMID- 2261644 TI - Mutations in v-myb alter the differentiation of myelomonocytic cells transformed by the oncogene. AB - Chick myelomonocytic cells transformed by the v-myb oncogene-containing viruses E26 and AMV differ in that the former resemble myeloblasts and express the v-myb regulated granulocyte-specific mim-1 gene, while the latter resemble monoblasts and are mim-1 negative. We constructed a series of AMV-E26 chimeras and localized the critical differences between these viruses to three point mutations within the second repeat of the v-myb DNA binding domain. These three positions are altered in the v-myb protein of AMV relative to the proteins encoded by c-myb or E26 v-myb. Back mutating AMV v-myb at any of these three sites restored the oncogene's ability to activate the mim-1 gene. Surprisingly, two of these changes led to the transformation, in vitro and in vivo, of cells having a promyelocyte like phenotype. These results indicate that different forms of v-myb impose alternate phenotypes of differentiation on transformed myeloid cells, probably by regulating unique sets of differentiation-specific genes. PMID- 2261646 TI - Translational inactivation of RNA function: discrimination against a subset of genomic transcripts during HBV nucleocapsid assembly. AB - Hepatitis B virus (HVB) is the prototype member of the hepadnaviridae, a family of small enveloped DNA viruses that replicate by reverse transcription. Assembly of replication-competent HBV nucleocapsids is based on specific interactions between the core protein, the product(s) of the P gene, and the RNA pregenome, which is marked for encapsidation by containing a sequence near its 5' end that acts in cis as an encapsidation signal. However, HBV produces several additional, almost identical, genomic transcripts that also bear the encapsidation sequence, but that are not encapsidated. The mechanism underlying this selection process has remained mysterious. Here we demonstrate that translating 80S ribosomes (but not scanning 40S ribosomal subunits) advancing into the encapsidation signal prevent its functioning. This finding reveals translational modulation of RNA function as a further regulatory mechanism employed by hepadnaviruses to utilize efficiently the restricted coding capacity of their extremely compact genome. PMID- 2261645 TI - The dynamics of protein phosphorylation in bacterial chemotaxis. AB - The chemotaxis signal transduction pathway allows bacteria to respond to changes in concentration of specific chemicals (ligands) by modulating their swimming behavior. The pathway includes ligand binding receptors, and the CheA, CheY, CheW, and CheZ proteins. We showed previously that phosphorylation of CheY is activated in reactions containing receptor, CheW, CheA, and CheY. Here we demonstrate that this activation signal results from accelerated autophosphorylation of the CheA kinase. Evidence for a second signal transmitted by a ligand-bound receptor, which corresponds to inhibition of CheA autophosphorylation, is also presented. We postulate that CheA can exist in three forms: a "closed" form in the absence of receptor and CheW; an "open" form that results from activation of CheA by receptor and CheW; and a "sequestered" form in reactions containing ligand-bound receptor and CheW. The system's dynamics depends on the relative distribution of CheA among these three forms at any time. PMID- 2261647 TI - [Evoked motor potentials in the diagnosis of multiple sclerosis]. AB - The authors examined evoked motor potentials (MEP) of the upper extremities in a group of 43 patients with multiple sclerosis using transcranial cortical and spinal stimulation. As abnormal they rated a prolongation of the motor conduction time by more than 3 sigma above the mean value recorded in the control group or when the response could not be evoked. The central motor conduction time between the cortex and cervical spine was abnormal in 76.7% of patients. The authors did not find a correlation between the severity of the paresis and the degree of electrophysiological abnormality. In frust and mild pareses the sensitivity was 80%. The frequency of abnormalities correlated with the degree of the diagnostic certainty. In patients with a probable diagnosis (according to Poser) abnormalities were present in 41.6%, when the diagnosis was certain, in 90.3%. In prolongation of the time of central motor conduction among all abnormalities 65.1% were due to prolonged motor conduction and in 27.9% the response could not be evoked. MEP examination is a sensitive technique for the detection of clinical and subclinical lesions and as to its sensitivity it is better than visual EP. PMID- 2261648 TI - [Somatosensory evoked potentials in the diagnosis of multiple sclerosis]. AB - The authors examined SEP in a group of 54 patients with the clinical diagnosis of SM. The sensitivity of the test in SEP of the median nerve was 68%, in SEP of the tibial nerve 78%. Concurrent use of both techniques revealed an abnormality in 83%. Subclinical abnormalities were present in 28% (median nerve) and 24% resp. (tibial nerve) of the patients. In case of a clinical disturbance of sensitivity the SEP finding was normal in 10% of the patients. A typical abnormality in SM was the absence of spinal responses and prolongation of the central conduction time. In 41% of the patients with an abnormal finding the abnormality was unilateral. The authors discuss possibilities of topical diagnosis of sensitive lesions by means of SEP. PMID- 2261649 TI - [Brainstem auditory evoked potentials in patients with multiple sclerosis--use of 2 stimulation frequencies]. AB - The authors examined Brainstem acoustic evoked potentials at different frequencies of repeated clicks (10, 15, 20, 30 and 50 Hz) in 30 healthy subjects (18 men, 12 women, age 12-50 years) and in a group of 89 patients with the diagnosis of multiple sclerosis (28 men, 61 women, age 16-55 years). Examination of the control group revealed that an increase of the stimulation frequency from 10 to 50 Hz leads to a significant prolongation of the absolute latencies of BAEP waves (in particular V wave), as well as inter-peak latencies (in particular I-V) and to a reduction of the amplitude of waves I and V, which was, however, significant only in wave I. The differentiability of some waves, in particular late ones was reduced. For these changes a zone of normal values was assessed. In patients with multiple sclerosis at a stimulation frequency of 10 Hz the most frequent abnormality of BAEP was a prolongation of the latency of the V wave and of I-V resp. At a stimulation frequency of 50 Hz the ratio of responses with undifferentiable waves V or III and V increased. The increase of the stimulation frequency from 10 Hz to 50 Hz led to a higher detection rate of abnormal BAEP findings in the whole group from 31% to 51% (p less than 0.001), in the sub-group of patients with a clinical lesion of the stem from 43% to 65% (p less than 0.01), in the sub-group without a clinically obvious lesion from 23% to 40% (p less than 0.01). In the sub-group of patients with a suspect diagnosis of multiple sclerosis, but without a clinically obvious symptomatology of the stem the detection rate of abnormal findings increased from 27% to 35% (NS). Based on their results, the authors are in favour of those views reported in the literature which consider the application of two stimulation frequencies during BAEP examinations useful for diagnostic purposes and recommend its inclusion in routine BAEP examinations of patients with multiple sclerosis, or suspect multiple sclerosis. PMID- 2261650 TI - [Electrophysiology of myoclonus]. PMID- 2261651 TI - [Classification of myoclonus]. PMID- 2261652 TI - [Changes in circulation of the blood in cerebral arteries in relation to age]. AB - The authors examined 12 people under 40 years and 12 above 40 years, mostly healthy volunteers. They investigated the rate of blood flow in the median cerebral artery after compression of the homolateral and contralateral internal carotid. They found that in more advanced age the rate of flow in the mentioned arteries is significantly reduced. During compression tests in more advanced age the decline in the flow rate is more marked in the median cerebral artery on the side of compression. In the other arteries the flow is promoted but the age dependence is not marked. The authors conclude from these findings that with advancing age the possibilities of autoregulation deteriorate more than those of the collateral circulation via Willis' circle. PMID- 2261653 TI - [Approaches to the treatment of subarachnoid hemorrhage under the present circumstances. Report of the panel discussion at the 4th Congress of Young Neurologists in Pec pod Snezkou, June 4 1989]. PMID- 2261654 TI - [Psychiatric care under the new conditions]. AB - The authors discuss the foreseen development of psychiatry under new conditions. They assume a new administrative set-up of the country, the introduction of health insurance and the establishment of a medical chamber (equivalent of Royal Colleges). In ambulatory care they assume that the hitherto existing policlinical system will be replaced by independently working specialists. In addition a part will be played also by specialized ambulatory psychiatric care in psychiatric in patient institutes and in semimural institutions (psychiatric day sanatoria, therapeutic workshops etc.). Psychiatric in-patient treatment still is concentrated in psychiatric sanatoria. It is, however, necessary that they should be legally independent and change their working style. They must apply humane and social principles and get rid of control work and repressive approaches; hospitalization should be only voluntary. At the same time social control is necessary as well as collaboration with charitative and religious organizations and new developing, independent initiatives. Another prerequisite of these changes is revision or amendement of some contemporary legal provisions. PMID- 2261655 TI - [The psychopathologic picture of incipient schizophrenia in the male population at approximately 20 years of age]. AB - As the diagnosis of initial schizophrenic psychosis is sometimes difficult and the diagnosis of schizophrenia is based on psychopathological characteristics the author used the relative homogenity of their cases for comparison with various known concepts and scales in an attempt to contribute to the serious problem of assessment of this nosological unit. Psychopathological descriptions of 45 cases of first hospitalizations on account of schizophrenia of men aged 18-24 years were investigated with regard to E. Bleuler's and Schneider's concept, with regard to the BPRS scale of Overall and Gorham and Carpenter's scale. The stability of "narrowly" set diagnoses of schizophrenia during short--term hospitalization (mean 48 days) verified catamnestically in 31 patients in 87% of whom the diagnosis was confirmed. By collection of symptoms and their classification an inventory of symptoms was assembled--890 terms, on average 20 symptoms per patient. Comparison of agglomerations of synomyms of symptoms with the above mentioned concepts of schizophrenia, simplified for the needs of the present work to a list of symptoms, proved useful also in case of the uncommon ex post application to BPRS systems and to Carpenter's approach. Schneider's symptoms of first order were found in the investigated group of schizophrenias in 75% of the cases. In the discussion the author deals briefly with problems of diagnosis of "fresh" schizophrenic psychoses in the selected group, in particular with regard to the post--adolescent developmental stage. PMID- 2261657 TI - [Approaches in the clinical classification of alcoholism from the historical perspective]. PMID- 2261656 TI - [Tics in childhood]. AB - Tics belong to the most frequent hyperkineses of child age. Their prevalence is reported as 4-28%. In our literature tics are still listed in the group of child neuroses although their organic aetiology is generally accepted. Tics are considered a continuum of complaints from transient tics in childhood to Tourette's disease (Gilles de la Tourette syndrome). As part of a catamnestic investigation 131 children with tics were followed up, all hospitalized at the paediatric department of the psychiatric clinic in Olomouc in 1968-1988. A prognostic evaluation was possible in 63 patients at the age of 15-29 years (group B). In the majority of patients the tics manifested themselves first at the age of cca 7 years. The group comprised a large percentage of children with the diagnosis ADDH (58.9%). Dynamic comparison revealed that in recent years the number of children in this group with tics increased. Evaluation of the therapeutic approach before hospital admission during hospitalization and during subsequent ambulatory treatment provided evidence of the further development of the disease, as the development of symptoms and increasing impact of psychosocial consequence frequently called for administration of incisive neuroleptics in ambulatory treatment, administered in subsequent years. The greatest proportion of patients terminated ambulatory treatment at the age of 10-15 years which, however, did not reflect regression of complaints. Prognostic evaluation provided evidence that 38% of the patients recovered completely by the time of the check up examination, 62% have occasional complaints (relapses persisting for several days), only 14% have permanent manifestations of tics. Some patients need event in adult age prolonged maintenance pharmacotherapy. PMID- 2261658 TI - [The "open door" system in psychiatry]. AB - The authors describe the situation which developed as a result of construction work, when the grounds of the psychiatric clinic were open. Before that time there were during a five-year period on average 2.2 escapes per year; despite an unaltered regime of the patients and unaltered supervision there was not a single escape. This is in favour of an "open door system" in psychiatry, with the possibility to apply it in future rationalization activities. PMID- 2261659 TI - [Ethical problems in psychiatric intervention in hopeless conditions in patients under the care of somatic specialists]. AB - Psychiatric intervention is usually requested for patients in other hospital departments in case of exacerbation of an intercurrent mental disease, in case of the development of a symptomatic mental disorder directly associated with the basic disease, and finally in case the patient refuses to cooperative with the attending staff. If in the former two indications the psychiatric intervention has a causal or complementary character in the latter the psychiatrist either makes up for the deficit of professional ethics of another specialist, provides an alibi for his possible failure, or objectively the sequelae ensuing from refusal of the intended intervention. The decision of the psychiatrist is influenced more by legal norms and general finally decides with forensic responsibility on the ability of the patient to evaluate ethic principles than evaluation of actual psychopathology. The results must, however, always be based on a spotless professional approach oriented on the mental health or the patient and his right to decide on his own integrity. Case--histories demonstrate the complexity of this decision and responsibility transferred often to the psychiatrist. PMID- 2261660 TI - [Psychoanalytic theory of personality and its use in practice. I]. AB - Psychoanalysis is concerned with investigation of endopsychic phenomena; using its own methods, it expresses hypotheses on its origin and functioning. These hypothese and their practical application are the subject of the submitted work. In the first part the author deals with the historical development of psychoanalytical theories and the possibility of a systemic approach in the construction of the comprehensive model of the psychic apparatus. The author explains Freud's theory and models corresponding to it as well as more recent ego psychological theories. In the conclusion she outlines a pattern of the development of objective relations which is in the background of the developmental trends of all psychic functions. PMID- 2261661 TI - [Psychoanalytic theory of personality and its use in practice. II]. AB - In the first part Freud's clinical theories and models and the ego psychological theory were described from which ensues a general pattern of objective relations. The second part of the paper attempts a synthesis of the most important psychoanalytical theories, the creation of a uniform model of psychic functioning using an epigenetic pattern. The author analyzes in more detail developmental trends of these mental functions which are considered in psychoanalysis decisive for adaptation. The developmental trends are divided into stages which correlate with stages of the development of objective relations. The developmental stages and transformations of specific psychological functions are presented by means of rectangular coordinate graphs. In the conclusion an epigenetic pattern of the foreseen development of personality is presented, a hierarchical model of modes of personality organization. PMID- 2261662 TI - [Adaptation problems in old age]. AB - The authors summarize available literature concerned with some problems of aging and old age. Attention is devoted in particular to factors which have an adverse impact on this process such as loss of the partner, retirement, disintegration of the home, reduced activity, etc. Some typical diseases of old age are mentioned. The authors emphasize that it is not enough to ensure economic and biological needs. Attention is paid in particular to problems of psychosocial adaptation of old people when going to a different, though sometimes more secure environment. Adaptation responses in the mental sphere may be sometimes very serious and may have tragic consequences for old people. As in contemporary society change of environment on social and health grounds is relatively frequently necessary, the authors summarize the literature on this problem and give an account of views how to prevent sequelae of impaired adaptation or how to mitigate them. PMID- 2261663 TI - [Antonin Marek--his importance for the beginning of new Czech psychiatric and psychological terminology]. AB - The author recalls a representative of the generation of the Czech National Revial, Antonin Marek (1785-1877). He mentions some Czech words which are important also for psychiatry, which created by A. Marek or which he introduced into modern Czech. Finally he quotes some passages from his work (1844) concerned with psychiatric problems. PMID- 2261664 TI - Acceptance of a psychiatric screening questionnaire by general practice attenders. AB - The general health questionnaire (GHQ) is a self-reporting psychiatric screening questionnaire which has been tested and validated in a number of languages and cultural settings. The translated and validated 30 item GHQ was given to a selected sample of women between 15 and 49 years attending a suburban general practice, as a part of a study on emotional disorder. The acceptance of the questionnaire was high with a compliance of 91.5% from those who were invited to participate. The majority of respondents showed much interest and willingness in filling in the questionnaire. PMID- 2261665 TI - A survey of the thermal environment, sound and illuminance in an iron and a steel foundry and related health effects. AB - The thermal environment and the workers' physiological response to heat were monitored throughout the casting process in two foundries. Of the 86 thermal observations in the iron foundry, 25 (29%) exceeded the heat stress index set by Occupational Safety and Health Administration (OSHA) advisory committee in 1974. In the steel foundry during a steel casting the environmental thermal measurements remained above the standard. The workers' physiological indices of heat strain as measured by pulse rate and body temperature rarely showed excursions above limits recommended by World Health Organization (WHO) in 1969. The environmental noise levels exceeded the standard in certain foundry operations. A significant hearing threshold shift was observed at 4 kHz among the foundry workers when compared with non-exposed controls. The illuminance in both foundries was below values recommended by the illuminating Engineering Society, in 1977. The prevalence of lens and corneal opacities among workers in the iron foundry was 32.5% and 30.0% respectively, which was significantly higher than that of the workers in the steel foundry and non-exposed controls. PMID- 2261667 TI - Dengue haemorrhagic fever. PMID- 2261666 TI - Prevalence of dental fluorosis in four selected schools from different areas in Sri Lanka. AB - The prevalence of dental fluorosis in four selected schools from different areas in Sri Lanka was investigated by dental examination of 377 school children aged 14 years. In the endemic zone the prevalence of dental fluorosis was 51 to 78% while in a non-endemic area it was 5.4%. There were no significant sex differences in the prevalence of fluorosis. Attention is drawn to the need for using non-fluoridated tooth-paste in areas where dental fluorosis is common. The problem could be further aggravated in the future by the use of water from tube wells in these areas which are known to contain higher concentrations of fluoride than those from shallow wells. PMID- 2261668 TI - Glycosylated haemoglobin. PMID- 2261669 TI - Healthcare in Sri Lanka: review of the eighties, outlook for the nineties. PMID- 2261670 TI - [Nurse and the modern hospital design]. PMID- 2261671 TI - [Immunological type of multiple myeloma and care of the patients]. PMID- 2261672 TI - [Nursing care of complications of hepatic abscess]. PMID- 2261673 TI - [Mental care at home and the relapse of schizophrenia]. PMID- 2261674 TI - [Experience on the control of hemodilution degree for extracorporeal circulation]. PMID- 2261675 TI - [Blood specimen collection in patients with cyanotic congenital heart disease]. PMID- 2261676 TI - [Nursing care in patients with abdominal tumor with hyperthermia]. PMID- 2261677 TI - Comparative hemodynamics and cardiovascular effects of endotoxin and platelet activating factor in rat. AB - We have compared the cardiovascular effect of endotoxin with platelet-activating factor (PAF) in rats. Endotoxin injected into perfusate of isolated rat heart did not induce significant changes in heart function, whereas PAF induced elevation of coronary perfusion pressure (CPP), decrease in ventricular pressure (VP), decrease in coronary flow (CF), but no significant changes in heart rate (HR). Neither endotoxin nor PAF caused contraction or relaxation of isolated rat arteries. However, endotoxin in the presence of macrophages caused contractions of rat aortic strips. These contractions were potentiated when platelets were present in the macrophage preparation. PAF in the presence of platelets caused profound contraction of the aortic strips, and this action of PAF was entirely blocked by either PAF antagonists or thromboxane antagonists. Injection of endotoxin into rats (i.v.) caused a decrease in blood pressure (BP) without significantly affecting the HR. At higher concentrations (greater than or equal to 10 mg/kg), endotoxin caused ventricular tachycardia (VT) associated with ventricular fibrillation (VF). PAF in vivo caused a rapid and sustained decrease in BP, with an ED50 of 3 micrograms/kg. PAF antagonists significantly prevented overall mortality induced by PAF and short-term endotoxin-induced mortality, but not the long-term (week) mortality. Endotoxin (10 mg/kg) injected into rats caused the release of PAF into the circulation, reaching a maximum after 2-5 min. Tritiated PAF injected into rats i.v. was metabolized over 60 min into lyso-PAF (approximately 30%), acyl-PAF (approximately 10%), and some degraded products (approximately 10%), and the remainder was found in the form of PAF. The results of the present study suggest that PAF may play a significant role in the pathogenesis of endotoxin shock. The action of PAF requires the participation of cells such as platelets, macrophages, neutrophils, and monocytes and involvement of arachidonic acid metabolites. PMID- 2261678 TI - Comparative evaluation of the effects of felodipine, hydralazine, and naloxone on the survival rate in rats subjected to a "fixed volume" model of hemorrhagic shock. AB - Felodipine, a dihydropyridine calcium antagonist with potent arteriolar dilator properties, has been shown to enhance renal, mesenteric, coronary, and cerebral blood flows in intact animals as well as in man and to prevent deterioration of renal and mesenteric blood flows in Wiggers' model of hemorrhagic shock in dogs. In the present studies, efficacy of felodipine on 72 hr survival of rats subjected to an acute withdrawal of 40% of the blood volume was investigated. Shed blood was not reinfused in the present studies. Felodipine, whether administered before or after hemorrhage, facilitated dose-dependent increases in the survival rate up to 95%, whereas in the vehicle-treated group, the survival rate was 33%. Hydralazine, also an arteriolar dilator, in equi-hypotensive doses was not as effective as the calcium antagonist. Effects of felodipine are comparable to that of naloxone in enhancing survival. These data suggest that the salutary effects of felodipine can be related to its calcium antagonistic as well as arteriolar dilator properties. PMID- 2261679 TI - Migration of mast cells in the developing rat brain. AB - Mast cells are known to derive from the bone marrow and enter the tissues as immature cells which differentiate under local microenvironmental factors. However, it has not been known how and when these cells enter the brain; moreover, the localization of mast cells in the developing rat brain differs from that of the adult animal. Our anatomical and morphological observations showed that during late embryonic stages and the first 11 days after birth, rat brain mast cells were exclusively concentrated within the pia mater surrounding the diencephalon, the choroid fissure and within the choroid plexus. Histochemically these cells contained only a few toluidine blue metachromatic granules, suggesting a 'mucosal' phenotype and the absence of heparin. Later, during a transitional phase from postnatal day 11 to 13, these cells migrated along blood vessels of the fimbria, the hippocampus and the penetrating vessels of the thalamus into the dorsolateral and posterolateral thalamic nuclei. These cells contained more metachromatic granules, and from day 13 on, they assumed their adult perivascular localization within the thalamus with numerous metachromatic granules similar to those described for mature thalamic and serosal mast cells. PMID- 2261680 TI - Timetables of cytogenesis in the rat subfornical organ. AB - Timetables of neurogenesis and ependymal cell production in the rat subfornical organ (SFO) were determined by examining the offspring of pregnant rats injected with [3H]thymidine on E13-E14, E14-E156, ... E21-E22, respectively. The proportion of postmitotic cells originating each embryonic day was determined by analyzing, in the adult offspring, the progressive reduction in the proportion of labeled precursors from the maximum amount seen in the E13-E14 group. Neurogenesis was found to occur over an extended period of time, beginning on E12 and continuing through E21. Ependymal cells were generated E15 through E21. Both neuron and ependymal cell production occurred in a triphasic pattern and followed an anterior (older) to posterior (younger) gradient. The anterior to posterior production gradient may be related to the morphological variation which exists along this plane. A production gradient intrinsic to a particular levels was found only in the posterior SFO, where peripheral neurons form earlier than core neurons. That neurogenetic gradient may be related to the core-periphery topographical patterns found in other studies, and suggests that the core neurons, since they are among the last to be formed, may be interneurons. PMID- 2261681 TI - Age-dependent changes in acetylcholinesterase activity in the primary somatosensory cortex of the cat. AB - As cortical reorganization in cat somatosensory cortex has been shown to be age dependent and acetylcholinesterase and acetylcholine have been implicated in the shaping of sensory responses during the developmental process, we decided to investigate the biochemical changes that occur in acetylcholinesterase during postnatal development of the primary somatosensory cortex in normal cat. Somatosensory cortices were removed from cats at various ages between 4 and 144 postnatal days. Three fractions (total, membrane-bound and soluble) were analyzed for activity (esterase assay and sedimentation analysis) and amount of acetylcholinesterase (electrophoresis). Results indicated that both esterase activity levels and amounts were characterized by 4 distinct phases which included a large step increase in all fractions between postnatal days 10 and 12: a gradual rise between days 12 and 28: a 'dip' during the 42- to 82-day interval, and a subsequent recovery. Results may be attributed to concomitant developmental events. Furthermore, we suggest that the observed changes may relate to age dependent differences in somatosensory cortex reorganization that occur after spinal cord transection. PMID- 2261682 TI - Transplant connectivity in the rat cerebral cortex. A carbocyanine study. AB - Previous reports suggest that the specificity of connectivity between cortical areas and their related thalamic nuclei is established during development. We have used heterotopic E15, E17 and E19 transplants to determine at which embryonic age the cortex is mature enough to establish such specific connections. Carbocyanine DiI or Fluoro-Gold were used for labelling transplants. Efferent cortico-cortical, callosal and collicular connections were observed when DiI was applied in fixed tissue. Thalamic nuclei were labelled when DiI was used 'in vivo' or the transplants were labelled with Fluoro-Gold. The connections of the transplants were those corresponding to the area in which the transplants were placed. This suggests that up to E19 the embryonic cortex is too immature to define the specific thalamo-cortical connections. PMID- 2261683 TI - Critical periods to ethanol exposure during early neuroembryogenesis in the chick embryo: cholinergic neurons. AB - The acute and chronic effects of ethanol on cholinergic neuronal expression were studied in the chick embryo during early neuroembryogenesis using choline acetyltransferase (ChAT) activity as a cholinergic marker. Ethanol administered to embryos in ovo on day 1 (E1) produced a 30% decrease in ChAT activity, while ethanol administration on day 3 elicited no significant change. Similar effects were produced by ethanol on ChAT activity in the spinal cord. The decrease in ChAT activity in both brain and spinal cord was not accompanied by a significant change in protein content. Of significance were our findings with chronic ethanol treatment: in embryos treated from E1 to E5 and sacrificed at E6, ChAT activity was decreased. In contrast, in embryos treated similarly but sacrificed at E8 ChAT activity was increased. These findings establish that the critical period of cholinergic neuronal sensitivity to ethanol is confined to E. Moreover, the increase in ChAT activity observed after chronic ethanol treatment indicates that the developing neurons have the capability to adapt to ethanol. This apparent adaptation results in overcompensation, as reflected by the increase in ChAT activity. Whether this overcompensation is at the expanse of another neuronal population remains to be investigated. PMID- 2261684 TI - Thalamic axons confer a blueprint of the sensory periphery onto the developing rat somatosensory cortex. AB - In order to study the role of afferents in the maturation of cortical axons projecting from the ventrobasal thalamic complex (VB) to the barrel field (SI) cortex were labeled with the carbocyanine dye DiI, in aldehyde-fixed embryonic and newborn rat brains. Our results reveal that the first few thalamic axons are in the cortical plate by embryonic day (E) 19. Between E19 and the day of birth (E21 = PND 0), layers V and VI differentiate from the lower part of the cortical plate. On PND 0, a plexus of growth-cone tipped thalamic axons is present within the cortical plate and a few VB fibers have reached the marginal zone. Increasing numbers of thalamic afferents invade and ramify within the cortical plate on PND 1 and, over the course of the next 24 h, form a vibrissa-specific pattern in the lower part of this zone, prior to the differentiation of layer IV into a distinct lamina. This periphery-related organization is exhibited by VB afferents earlier than reported for other afferents to the cortex, by glia- or neuron-associated extracellular elements or by the cytoarchitectonic specializations (barrels) of stellate cells. Our observations, in conjunction with the previous studies, demonstrate that thalamic afferents may have a pivotal role in determining the morphological specification of the primary somatosensory cortex. PMID- 2261685 TI - Difference in distribution of microtubule-associated proteins 5a and 5b during the development of cerebral cortex and corpus callosum in cats: dependence on phosphorylation. AB - MAP5, a microtubule-associated protein characteristic of differentiating neurons, was studied in the developing visual cortex and corpus callosum of the cat. In juvenile cortical tissue, during the first month after birth, MAP5 is present as a protein doublet of molecular weights of 320 and 300 kDa, defined as MAP5a and MAP5b, respectively. MAP5a is the phosphorylated form. MAP5a decreases two weeks after birth and is no longer detectable at the beginning of the second postnatal month; MAP5b also decreases after the second postnatal week but more slowly and it is still present in the adult. In the corpus callosum only MAP5a is present between birth and the end of the first postnatal month. Afterwards only MAP5b is present but decreases in concentration more than 3-fold towards adulthood. Our immunocytochemical studies show MAP5 in somata, dendrites and axonal processes of cortical neurons. In adult tissue it is very prominent in pyramidal cells of layer V. In the corpus callosum MAP5 is present in axons at all ages. There is strong evidence that MAP5a is located in axons while MAP5b seems restricted to somata and dendrites until P28, but is found in callosal axons from P39 onwards. Biochemical experiments indicate that the state of phosphorylation of MAP5 influences its association with structural components. After high speed centrifugation of early postnatal brain tissue, MAP5a remains with pellet fractions while most MAP5b is soluble. In conclusion, phosphorylation of MAP5 may regulate (1) its intracellular distribution within axons and dendrites, and (2) its ability to interact with other subcellular components. PMID- 2261686 TI - Sexual dimorphism in the bed nucleus of the accessory olfactory tract in the rat. AB - This work investigates the existence of sex differences in the volume and number of neurons and glial cells in the bed nucleus of the accessory olfactory tract (BAOT). Males showed larger volume and number of cells than female rats. Early postnatal (day 1 after birth) orchidectomy in males, and androgenization in females, reversed these differences. No sex differences were found in BAOT glial cells. The sexual dimorphism found in the neuron/glial cell ratio reflects sex differences in neuron number. The existence of sexual dimorphism in the BAOT supports our earlier hypothesis which states that the vomeronasal system (VNS) is sexually dimorphic. PMID- 2261687 TI - Kindling in developing animals: expression of severe seizures and enhanced development of bilateral foci. AB - In adult rats, alternating stimulations between two limbic sites can result in one site kindling normally, while the other is retarded in an early non generalized kindling stage. This phenomenon has been named kindling antagonism. In this report, we present data indicating that kindling antagonism does not occur in 16-day-old rats. Instead, 16-day-old rats receiving alternating stimulations in the amygdala and hippocampus develop progressively more severe seizures. Kindling with alternate stimulations is elicited at a much faster rate at the two foci compared to kindling from a single site, either the hippocampus or amygdala. All groups develop generalized seizures including seizure stages 6 and 7, consisting of wild jumping, running with vocalizations and tonus. These seizures appear after relatively few stimulations in the pup, in comparison to the adult. The results indicate that the immature brain is less able to suppress the generalization of seizures than the adult. The age-specific enhanced development of bilateral foci may be due to underdeveloped inhibitory systems and may underlie the propensity of the immature CNS to develop multifocal seizures. PMID- 2261688 TI - Soluble and membrane-bound factors together account for target dependence of cultured parasympathetic neurons. AB - The survival of avian ciliary ganglion (CG) neurons in culture depends upon an exogenous supply of trophic factor(s). Skeletal muscle, a normal ganglionic target tissue, is a well documented provider of survival-promoting activity, although the molecular basis for this ability to foster neuronal survival has not been thoroughly investigated. To identify the source of skeletal muscle support, dissociated neurons were plated into microwells containing either: a basal, trophically deficient medium; live pectoral muscle myotubes; medium conditioned by myotubes; membrane remnants of osmotically lysed myotubes; or, membrane remnants and conditioned medium. Neurons remaining in culture were counted after 1, 2, 5, and 7 days. The results reveal that neuronal survival is supported by both muscle conditioned medium and the membrane remnants of cultured myotubes. Each of these alone provides for only partial survival, while both combine to equal the activity of live myotubes. Treatment of the lysed membranes with either 1.5 M NaCl and/or 15 U heparin removed only 50-60% of the activity, suggesting that multiple factors are involved in the neuronal support obtained from lysed myotubes. This is in contrast to fibroblast remnants, which support some neuronal survival, but whose activity is wholly removed by NaCl. Conditioned medium also contains a heparin binding component which accounts for approximately 60% of its activity. These results indicate that full trophic support from the cultured target tissue requires at least two distinct active agents. The experiments further suggest that the target-derived factors responsible for neuronal survival in culture, and perhaps in vivo, are both soluble and membrane-associated molecules. PMID- 2261689 TI - Clinical biochemistry of preeclampsia and related liver diseases of pregnancy: a review. PMID- 2261690 TI - Amino acid profiles by HPLC after filter paper sampling: 'appropriate technology' for monitoring of nutritional status. AB - This paper describes a rapid analysis of free amino acid levels in capillary blood samples using a modified HPLC system. Capillary whole blood (25 microliters) is dried on a filter paper, extracted and the equivalent of 0.25 microliter of the initial blood sample is used for each amino acid analysis. Nineteen free amino acid levels are determined with a reproducibility of better than +/- 10% for the entire procedure of sampling, preparation and analysis, with the exception of ornithine (+/- 19%) and lysine (+/- 12%). Cystine and proline cannot easily be determined by this method. Alanine, tyrosine, methionine, valine, phenylalanine, isoleucine and leucine concentrations on the filter paper are unaltered after 1, 2 and 21 wk. Storage at room temperature should not be for longer than 2 wk, but storage at +4 degrees C, -18 degrees C and -70 degrees C is acceptable for 21 wk. This new micromethod seems to be a practical and reliable tool. Because of its simplicity and, above all, the need for a minimal amount of capillary blood, it is a valid means for the routine monitoring of amino acid profiles in sick preterm infants on different protein regimens. The sampling and storage methods are also examples of 'appropriate technology' for field studies of nutritional adequacy in population samples derived from infants. This is because centrifugation is not necessary and the fact that the relevant amino acids on the dried filter paper samples display high stability. PMID- 2261691 TI - A reversed-phase high-performance liquid chromatographic method for the determination of pyruvate dehydrogenase complex activity in human platelets and cultured skin fibroblasts. PMID- 2261692 TI - Interference of abnormal hemoglobins on the measurement of hemoglobin A1c by ion exchange chromatography. PMID- 2261694 TI - Gunn rats: a reproducible experimental model to compare the different methods of measurements of bilirubin serum concentration and to evaluate the risk of bilirubin encephalopathy. AB - Three groups of Gunn rats were studied: group 1 was perfused with bilirubin solution alone, group 2 was perfused with bilirubin and albumin solutions simultaneously, group 3 was perfused with bilirubin solution for 30 min then bilirubin and albumin solutions for the following 10 min. Our results indicate that (1) Gunn rats are a reliable experimental model to study the risk of bilirubin encephalopathy, (2) unbound bilirubin can enter the brain when albumin binding capacity is reduced, (3) and bilirubin binding capacity of serum for unbound unconjugated serum bilirubin is a better criterion than total serum bilirubin and erythrocyte bilirubin to evaluate the risk of kernicterus. This model could also be used to study variations of permeability of the blood-brain barrier and influences of drugs on bilirubin metabolism. PMID- 2261693 TI - Interaction between endogenous circulating sulfated-glycosaminoglycans and plasma proteins. AB - Interaction between endogenous 35S-labelled plasma glycosaminoglycans and proteins in murine plasma was demonstrated by coelution from gel chromatography of circulating 35S-labelled glycosaminoglycans with a wide range of plasma proteins. Autoradiography of electrophoretic tracing of proteins from 35S-sulfate labelled plasma showed that labelled glycosaminoglycans were associated with alpha 1, alpha 2, beta globulins and albumin, but not with gamma globulins. Analysis by gel chromatography on Sepharose CL-6B of delipidated 35S-labelled plasma after either proteolysis or beta-elimination, suggested that 35S-labelled glycosaminoglycan chains were covalently bound to proteins. Lipids were probably involved in the supramolecular assembly of GAGs with plasma proteins, as shown by hydrophobic interaction chromatography. In addition, strong, non-covalent interaction between glycosaminoglycan chains and proteins was responsible for the difficulty in extracting 'free' glycosaminoglycans from plasma. Consistently, ion exchange chromatography of 35S-sulfate labelled delipidated plasma after alkali treatment, revealed that the anionic properties of glycosaminoglycans were hampered when plasma proteins were present. PMID- 2261695 TI - Radioimmunoassay for sequence 38-54 of human progastrin: increased diagnostic specificity of gastrin-cell diseases. AB - Antisera were raised against fragment 38-54 of human progastrin. All of eight immunized rabbits responded, but only one (No. 2145) produced high-titer (3.2 x 10(4)) and high-avidity (Keff degrees = 1.2 x 10(12) l/mol) antibodies. A radioimmunoassay based on antiserum 2145 and monoiodinated gastrin-34 was specific for the N-terminal sequence of human gastrin-34. It measured concentrations of 9.7 +/- 1, 18.4 +/- 2 pmol/l (mean +/- SEM) and 1.553 (0.7-476) nmol/l (median (range], respectively, in sera from normal subjects (n = 20), patients with duodenal ulcer (n = 19), and Zollinger-Ellison patients (n = 8). Conventionally measured concentrations of carboxyamidated gastrins in the same sera were 21.4 +/- 1, 23.8 +/- 3 pmol/l (mean +/- SEM) and 0.833 (0.4-214) nmol/l (median (range)), respectively. The results show that radioimmunoassays specific for the N-terminus of human gastrin-34 discriminate between healthy subjects and patients with duodenal ulcer. The improved diagnostic specificity is due to co measurement of unprocessed and partly processed progastrins that occur in plasma of patients with duodenal ulcer disease and gastrinomas. We suggest that conventional gastrin assays are supplemented with assays specific for the N terminus of gastrin-34 in studies of duodenal ulcer disease. PMID- 2261696 TI - Radioimmunoassay for plasma neuropeptide-Y in physiological and physiopathological states and response to sympathetic activation. AB - A radioimmunoassay has been developed for measuring plasma neuropeptide-Y immunoreactivity using extraction on Sep-Pak C18 cartridges. Neuropeptide-Y concentrations (mean +/- SEM) in plasma from 15 normotensive individuals were 223.6 +/- 14.7 ng/l. Plasma concentrations were raised in 10 patients with heamodialysis-dependent chronic renal failure with values of 417.6 +/- 13.6 ng/l and in 3 patients with phaeochromocytoma the concentrations were 237 ng/l, 574 ng/l and 747 ng/l. Plasma neuropeptide-Y immunoreactivity was also measured in 10 normotensive individuals in response to a, hand-in-ice, cold pressor test. Despite an immediate significant elevation in blood pressure, neuropeptide-Y immunoreactivity was not significantly raised until after the removal of the hand from the ice by which time the blood pressure had returned towards the basal levels. This dissociation in neuropeptide-Y immunoreactivity and blood pressure responses probably reflects a delay in the diffusion of synaptic neuropeptide-Y into the general circulation. This study suggests that the measurement of neuropeptide-Y immunoreactivity may be a useful index of sympathetic activation. PMID- 2261697 TI - Evaluation of a simple method for the measurement of cytidine deaminase in serum and comparison with a reference method. AB - This study was designed to evaluate a cytidine deaminase (CD) assay modified to allow results to be achieved within one working day. Inter-batch variation for samples of mean (SD) CD activity, 10.2 (1.0) units, 17.5 (1.2) units and 31.7 (1.7) units were, 9.8%, 6.9% and 5.4% respectively (n = 26). The reference range (3.2-13.2 U) was similar in males and females and was independent of age. There was close correlation with a reference method (r = 0.96). The mean difference between methods was 2.7 U and the limits of agreement were -1.7 to 7.1 U. The results indicate that the short assay technique can produce results that are sufficiently accurate and precise to be clinically useful. PMID- 2261698 TI - Urinary polyamine and metabolite excretion by children with Zellweger's syndrome. AB - In order to investigate whether, due to a lack of peroxisomes, polyamine degradation is altered in patients with the cerebro-hepato-renal syndrome of Zellweger, we determined total, free and acetylated polyamines and some of their catabolites in urines of six patients and age-matched healthy children. The normal polyamine excretion patterns of the patients, compared to the control group, suggest that either the intracellular localisation of the polyamine degrading enzyme, polyamine oxidase, is not exclusively limited to peroxisomes or that the enzyme is located in the peroxisomal matrix. PMID- 2261699 TI - The effect of excess daily methionine intake on plasma homocysteine after a methionine loading test in humans. AB - Impaired homocysteine metabolism might be a risk factor for vascular disease. Peroral methionine loading and post-load determination of methionine and homocysteine in plasma has frequently been used for identifying subjects with genetically impaired homocysteine metabolism. However, a methionine-rich diet induces a more efficient homocysteine catabolism in the rat, which suggests that humans on diets with differing methionine content might respond differently to the methionine loading test. To study this we performed methionine loading in six healthy subjects before and after 2 wk of excessive daily methionine intake (300% of normal). On each occasion plasma homocysteine and methionine were measured at several intervals post-load. However, neither the methionine clearance nor the post-load homocysteine concentrations were affected by excess methionine. We conclude that variations in the daily methionine intake will not influence the methionine loading test. PMID- 2261700 TI - One-step solvolysis of 3-, 7- and 12-sulfated free and conjugated bile acids. PMID- 2261701 TI - A simple procedure to exclude false-positive galactose screening test results caused by antibiotics. PMID- 2261702 TI - The antiperinuclear factor. PMID- 2261703 TI - Depressed cutaneous cell-mediated immunity in early rheumatoid arthritis. AB - To study the role of cellular immunity in recent-onset rheumatoid arthritis (RA), 26 patients with early RA were examined by skin testing with seven common recall antigens. The skin test was performed before the administration of second-line antirheumatic therapy and was repeated after six months of medication. Controls included healthy individuals and patients without known immunological abnormalities or malignancies. 50% of the RA patients were classified as anergic compared to 7% of the controls. In the RA patients, depression of cell-mediated immunity was related to gender but not to disease activity. Anergic and reactive patients showed similar clinical improvement after six months of therapy. The frequency of anergy at six months was not statistically different from that before therapy. HLA-DR4 was more frequent in the reactive patient group (92%) compared with anergic patients (53%). We conclude that cell-mediated immunity is impaired in early RA but the impairment does not correlate with disease activity or with the response to treatment and does not return to normal during treatment with second-line antirheumatic drugs. PMID- 2261704 TI - Methylprednisolone has a preventive effect on the development of radiological changes, thickening and stiffening of the rabbit knee following immobilization. AB - The effect of methylprednisolone (MP), Depo-Medrol, on the development of radiologically detectable changes, i.e. thickening and stiffening in rabbit knees following a standard immobilization method, was investigated. The right knees of 34 rabbits were immobilized by a splint and an elastic bandage in extension for five weeks, whereafter the splint was removed. Twelve of the rabbits were given MP in the back muscles once a week during the immobilization period only and eight other rabbits were given diminishing doses during the immobilization period and also during the remobilization period. Marked radiologically detectable changes, stiffening, and thickening developed regularly in the immobilized knees of the rabbits which were not given MP. In the other rabbits MP had a significant preventive effect on the development of all these pathological signs. The degree of the effect of MP was related to the dose and to the administration period. The optimal effect was registered when MP was given initially in large but then gradually diminishing doses during the immobilization and the remobilization periods. PMID- 2261705 TI - Synergistic and additive effects of disease modifying anti-rheumatic drugs combined with chloroquine on the mitogen-driven stimulation of mononuclear cells. AB - The efficacy of azathioprine, methotrexate, cyclosporin, and d-penicillamine alone and in combination with chloroquine was quantitated in an in vitro system, with the use of mitogen-stimulated human peripheral blood mononuclear cells. A concentration-dependent effect was found for each of these drugs. The effect of adding chloroquine to azathioprine or methotrexate was roughly the same as the effect of these cytostatics alone. However, the combined effect of chloroquine and cyclosporin exceeded the sum of the effects of the individual drugs, which indicates synergy, whereas the combination of chloroquine with d-penicillamine resulted in antagonism. PMID- 2261706 TI - Sequential salivary scintigraphy in Sjogren's syndrome: proposal for a new method of evaluation. AB - Thirty-seven non-elderly primary Sjogren's syndrome (I SS) patients, and 27 controls complaining of xerostomia and/or recurrent or persistent swelling of at least one parotid or submandibular gland due to other selected disorders, were studied. A new scintigraphic score (scsc) is proposed for a standardised semiquantitative evaluation of salivary involvement by qualitative sequential salivary scintigraphy (SSS), and is compared with two other well-known methods generally used for this purpose. The scsc proved to be much more suitable for such an evaluation: the other criteria did not allow us either to classify or to score a great number of cases. Furthermore, the scsc allowed us to obtain better SSS sensitivity (89.2%) and specificity (96.3%) values for I.SS (33 of the 37 I SS patients and 26 of the 27 controls were correctly classified by discriminant analysis, for scsc values greater than 8). This was made possible by the different "weights" which we assigned to the various glandular and oral parameters in the scsc determination. PMID- 2261707 TI - Muscle strength and aerobic capacity in primary fibromyalgia. AB - Twenty-six women with primary fibromyalgia were tested for muscle strength and for aerobic capacity and fatigue. Grip strength was measured with a manometer. In the patient group the grip strength was 58 +/- 22 kPa (mean +/- SD) versus 97 +/- 17 kPa in healthy matched controls (p less than 0.01). The patients performed a mean of 10 +/- 6 repetitions with maximal grip pressure (dynamic endurance work), while the controls performed 13 +/- 6 repetitions (p less than 0.01). The upper extremity was kept in a fixed position for 152 +/- 147 seconds in the patient group versus 413 +/- 244 seconds in the control group (static endurance work), p less than 0.004. Normal aerobic capacity (O2 ml/kg min) was found in the patient group. Expected fatigue values were determined by Borg's rating scale for perceived exertion according to the heart rate in a cycle ergometer test. There was a significantly higher mean fatigue score in the patient group as compared to the expected values (p less than 0.0001). PMID- 2261708 TI - Lymphokine activated killer (LAK) cell activity in the peripheral blood lymphocytes of systemic sclerosis (SSc) patients. AB - Lymphokine activated killer (LAK) cells, which arise from interleukin-2 (IL-2) activation of natural killer (NK) cells, are capable of lysing NK-resistant cell targets, including endothelial cells (EC). Since EC cytotoxicity is postulated to play a role in the pathogenesis of systemic sclerosis (SSc), experiments were performed to measure LAK activity in the peripheral blood lymphocytes (PBL) of 10 SSc patients and 10 normal controls. SSc patients had no significant spontaneous cytotoxicity against NK-resistant cell targets, including EC. After IL-2 stimulation in vitro, SSc patients and normal controls demonstrated cytotoxicity toward NK-resistant cell targets, including EC. This LAK-mediated EC cytotoxicity was actually lower for SSc patients than for normal controls. These studies do not preclude a role for LAK-mediated EC cytotoxicity in the pathogenesis of SSc, but demonstrate that LAK cells are not spontaneously present in circulating PBL. PMID- 2261710 TI - EPM-ROM Scale: an evaluative instrument to be used in rheumatoid arthritis trials. AB - Different tools are available for the measurement of functional status; however, only a few of them are based on the evaluation of the joint range of motion (ROM). This study is aimed at the design and evaluation of the measurement properties of a ROM scale to be used as an evaluative instrument in rheumatoid arthritis (RA) trials. The EPM-ROM Scale evaluates 10 distinct movements of the small and large joints. The score of each joint varies from 0 (full movement) to 3 (severe limitation) and the cut-off degrees of motion are, in general, based on the lack of ability to perform some determined activities of daily living. The test-retest characteristic of the scale was assessed by administering the scale twice, 5 days apart, to 35 RA patients. The product moment correlation was 0.775 (P less than 0.001). The cross-sectional construct validity of the scale was assessed by the concomitant scoring of the EPM-ROM Scale and the functional ability dimension of the Health Assessment Questionnaire (a reliable, valid and responsive instrument) in these patients. The product moment correlation was 0.518 (P less than 0.001). The evaluation of its longitudinal construct validity and responsiveness are now in progress. PMID- 2261709 TI - Sensorineural hearing loss in rheumatoid arthritis. AB - Hearing function was tested in 20 patients affected by rheumatoid arthritis. Audiological examination was performed by pure tone audiometry thresholds, tympanometry, a stapedial reflex threshold test and auditory brainstem responses (ABR). Hearing impairment was observed in 55% of patients. Conductive hearing loss and the absence of stapedius reflex were never recorded. Five patients with abnormal audiograms had normal ABR and normal stapedial reflex thresholds while 6 patients showed abnormalities in their audiograms, stapedial reflex thresholds test and ABR. Abnormal audiometric results associated with normal ABR are compatible with cochlea involvement, while abnormal audiometric results associated with an altered ABR and stapedial reflex test may be due to retrocochlear involvement. Sensorineural hearing loss appeared to significantly correlate with active disease and with the presence of rheumatoid factor. PMID- 2261711 TI - Rheumatoid arthritis with periarticular calcifications. AB - A rare case of rheumatoid arthritis with periarticular calcifications, lung involvement, pericarditis, nodules, Sjogren's syndrome and various drug side effects is described. Over a period of more than 10 years of observation, the patient's arthritis has been characterized by remissions and exacerbations. PMID- 2261712 TI - Uveitis in juvenile chronic arthritis. AB - About 20% of patients with juvenile chronic arthritis develop uveitis which is frequently bilateral. Risk factors for uveitis are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop cataract and/or glaucoma. The management of glaucoma is unsatisfactory, but the results of cataract surgery by lensectomy are good. PMID- 2261713 TI - Prevalence of IgM, IgA and IgG rheumatoid factors in juvenile rheumatoid arthritis. AB - Using an enzyme immunoassay, sera from 50 children with juvenile rheumatoid arthritis (JRA) and 39 controls were tested for IgM, IgA and IgG rheumatoid factors (RF). RF of the IgM and IgA isotypes were present in 11 (22%) patients, but in only one control (p = 0.008). IgG RF was present in the sera of 2 (4%) patients and in none of the controls (p = 0.21). Of the 22 patients with IgM RF or IgA RF, only 3 sera (14%) contained RF of both isotypes. IgM RF was more common in patients with polyarticular disease, while IgA RF was more common in patients with pauciarticular disease. These results indicate that IgM and IgA RF are present in a significant minority of JRA patients and suggest that there is independent expression of the respective RF isotypes. PMID- 2261714 TI - Septic arthritis due to streptococcus viridans. PMID- 2261715 TI - Reflections on the link between intestinal permeability and inflammatory joint disease. PMID- 2261716 TI - Doppler ultrasound studies: do they have a place in clinical obstetrics? PMID- 2261717 TI - Congenital stricture of the urethra. AB - Three patients with presumed congenital urethral strictures are presented. The strictures were all in the bulbar urethra and were demonstrated by micturating cysto-urethrography. A further child is described with a normal urethra in whom the appearances mimicked a proximal bulbar stricture. PMID- 2261718 TI - The significance of transverse folds in the gastric antrum. AB - Multiple fine transverse folds in the gastric antrum were found in three patients on double contrast barium meal. These folds were constant. Endoscopy and histology demonstrated gastritis in all patients. We suggest that this appearance is a radiological indicator of gastric inflammation. PMID- 2261719 TI - Morning or afternoon barium meal? Diurnal variation and the effectiveness of gastric mucosal coating during double-contrast studies. AB - The radiographs of 60 patients having double-contrast barium meal examinations were analysed by a linear analogue technique to assess variation in the quality of mucosal coating between morning and afternoon studies. No significant difference (P greater than 0.5) was found between morning and afternoon gastric mucosal coating. Factors that could in theory contribute to a diurnal variation are discussed. We conclude that afternoon DCBMs can be confidently booked and performed, in the knowledge that their diagnostic quality is not impaired. PMID- 2261720 TI - Correlation of 111indium WBC scintigraphy with ultrasound in the detection and assessment of inflammatory bowel disease. AB - 111Indium (111In) WBC scintigraphy is an accurate method of assessing the extent of inflammatory bowel disease. A prospective study was performed to determine the correlation of ultrasound scanning with 111In WBC scintigraphy in the assessment of inflammatory bowel disease. Eighty-three indium and ultrasound scans were performed in 57 patients. Forty-six patients had Crohn's disease and 11 patients had ulcerative colitis. The site extent of abnormality and the appearance of the bowel were recorded and compared to the findings on indium scintigraphy. Ultrasound detected 84% of indium-positive sites. If the rectum was excluded, sensitivity of detection rose to 91%. Three percent of indium-negative sites were positive on ultrasound. PMID- 2261721 TI - Indium labelled leucocyte scanning in pyrexia of unknown origin. AB - Pyrexia of unknown origin (PUO), the commonest cause of which is occult infection, represents a difficult diagnostic problem. Radiolabelled white cell scanning provides a non-invasive and potentially useful diagnostic tool in this condition, but its efficacy remains controversial. In a retrospective study, we analysed 30 111In white cell scans, performed between 1983 and 1988 in 25 patients with PUO, strictly defined as a fever of at least 3 weeks duration reaching 38.3 degrees C on more than three occasions and investigated in hospital for a minimum of 7 days. Eleven studies were on post-operative patients who, although developing fever within 1 week of surgery, satisfied the above criteria. Overall, the diagnostic sensitivity and specificity were 55% and 74% respectively, with an overall accuracy of 67%. This improved to 91% in the post operative patients compared to an accuracy of 52% in spontaneous PUO. Accuracy did not correlate with duration of symptoms, leucocytosis or index of clinical suspicion. In conclusion, although 111In white cell scanning is not particularly useful for the investigation of spontaneous PUO, it does have a role in post operative PUO. PMID- 2261722 TI - Biliary intervention via minicholecystostomy. AB - Minicholecystostomy was performed in 24 elderly patients, under local anaesthesia. All had symptomatic gallstones removed utilizing endoscopy and fluoroscopy. These procedures were well tolerated, with no significant complications, despite severe coexistent disease. One patient has had recurrent problems due to gallstones and one has died from disseminated malignancy. The remaining 22 are well and symptom-free. This combined surgical and radiological approach is a useful alternative procedure for patients with gallstones who are a poor risk for general anaesthesia. PMID- 2261723 TI - A comparison of modern imaging modalities in osteonecrosis of the femoral head. AB - Eleven symptomatic and seven asymptomatic patients, considered to be at high risk of osteonecrosis of the hip, were studied using plain radiography, scintigraphy, computed tomography (CT) with multiplanar reconstruction (MPR), and magnetic resonance imaging (MRI), to determine the precise roles of the various imaging modalities in detecting and staging femoral head osteonecrosis, and to evaluate the incidence in an asymptomatic high-risk patient group. Osteonecrosis was best detected by MRI and was particularly useful for the diagnosis of early disease when other imaging modalities were negative. It is recommended that MRI be performed for the detection of early osteonecrosis, while CT/MPR be used for accurate staging and treatment planning in the established disease. PMID- 2261724 TI - Critical evaluation of the radial head-capitellum view in acute elbow with an effusion. AB - The radial head-capitellum (RHC) view was performed in 125 patients following acute elbow trauma in which an elbow fat-pad effusion was visible on the standard antero-posterior and lateral projections. Seventy-four fractures were identified of which 63 (85%) involved the radial head. In only one case (1%) did the RHC view reveal a radial head fracture not seen on the standard two views. In eight cases (11%) the RHC view did not confirm a radial head fracture seen on the standard radiographs. Magnification blurring and the vertical orientation of the radial head fractures missed on the RHC view are responsible for this confusing situation. Routine use of the RHC view even in acute elbow trauma significant enough to produce an effusion is generally unhelpful and potentially misleading. PMID- 2261725 TI - Indolent gastric epithelioid leiomyosarcoma in Carney's Triad. AB - We report a patient with gastric epithelioid leiomyosarcoma and multiple pulmonary chondromata who remains asymptomatic 38 years after initial resection of the gastric tumour and 4 years after representation with recurrent tumour and multiple liver metastases. This represents an incomplete form of Carney's Triad, and illustrates the unusually indolent natural history of the gastric tumour in this condition. The radiological appearances are described. PMID- 2261726 TI - Mediastinal Castleman's disease: a missed pre-operative diagnosis? AB - Mediastinal lymphadenopathy is common and usually requires further evaluation with computed tomography (CT). This report describes a patient in whom the pattern of calcification within the lymph-node mass, seen on CT, might have suggested the diagnosis of Castleman's disease. Intense enhancement following intravenous contrast medium would indicate the vascularity of the lesion and add weight to the diagnosis. PMID- 2261727 TI - Numerous pulmonary metastases from renal cell carcinoma confined to the middle lobe. AB - Numerous pulmonary metastases entirely confined to one lobe are rare. A case is presented in which numerous pulmonary metastases from renal cell carcinoma were initially confused radiologically with lobar pneumonia. PMID- 2261728 TI - Low osmolar contrast media. PMID- 2261729 TI - Thrombolysis--a challenge for radiologists and surgeons. PMID- 2261730 TI - Ioversol in leg venography. PMID- 2261731 TI - In rheumatoid arthritis is compliance in physicians more of a problem than compliance in patients? PMID- 2261732 TI - Methotrexate therapy in rheumatoid arthritis. A two year prospective follow-up. AB - One hundred and thirty seven rheumatoid arthritis (RA) patients refractory to D penicillamine and some of them (15%) refractory to other slow active drugs were treated with oral methotrexate (MTX) (10-15 mg weekly). After 12-24 months of treatment, 94 and 74 patients respectively showed a significant improvement as judged by duration of morning stiffness (p less than 0.0001), grip strength (p less than 0.0001), degree of joint swelling (p less than 0.01) and tenderness (p less than 0.0001) compared to pre-treatment values. This clinical improvement was also associated with a decrease of erythrocyte sedimentation rate (p less than 0.001), decrease of C-reactive protein (p less than 0.0001) and with improvement of anaemia (p less than 0.05). No changes were seen in rheumatoid factor titres. Seventy-four of the patients were followed for up to 24 months. Thirty-one of them (23%) had complete remission and 43 (31%) had an excellent response. Adverse drug reaction during MTX therapy included: elevated liver enzymes in 34 patients, mucosal ulcers in 21, nausea and vomiting in 8, diarrhoea in 4, leukopenia in 2, interstitial pneumonitis in one, intestinal bleeding in one and finally septic arthritis in another patient. The majority of these side effects were resolved without sequelae. However, 15 patients (11%) with adverse drug reactions had to discontinue the treatment. Forty-one of our patients who received a cumulative mean dose of MTX of 1550.5 +/- 235.5 mg underwent a percutaneous liver biopsy. Ten patients had normal tissue, 12 had minimal changes, 13 nonspecific changes and 6 patients had mild fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261733 TI - Can treatment with methotrexate influence the radiological progression of rheumatoid arthritis? AB - We have recently reported that methotrexate (MTX) is an effective treatment of patients with refractory rheumatoid arthritis (RA) to second line medication. We showed that 54% of our patients continued having clinical benefit after 24 months therapy with MTX. In this study we evaluated pairs of hand radiographs from 35 patients taken before and after 24 months treatment. We used a scale scoring similar to Larsen's standard radiographs with minor modifications. No significant changes were observed in the overall scoring of the radiographs before (14.84 +/- 13.05) and after treatment (18.77 +/- 15.60) (p greater than 0.5). Of these 35 patients, 23 had a clinical remission and 12 had a good response. Twenty patients have shown a stabilization of erosions in radiographs while 15 showed a deterioration. No correlation was found between clinical response and radiological changes. We conclude that MTX does not appear to be a disease modifying agent, but may inhibit joint damage progression. PMID- 2261734 TI - Anti-Sm-RNP activity in sera of patients with rheumatic and autoimmune diseases. AB - The sera of various rheumatic and autoimmune diseases were examined for the presence of anti-RNP/Sm activity. An enzyme-linked immunosorbent assay (ELISA) was employed. Anti-RNP Ab's were detected in 18%, 20%, 28%, 16% of the sera of SLE, myasthenia gravis (MG), rheumatoid arthritis (RA) and thyroid diseases respectively. The anti-RNP Ab's belonged to the IgG and IgM isotypes. Most of the IgG anti-Sm antibodies were detected in SLE sera, but they were found also in two sera of MG and in one sera of RA patients. IgM anti-Sm antibodies were not found in SLE sera, but they were detected in low titer in MG, RA and autoimmune thyroid diseases. The activity against RNP and/or Sm was further confirmed by employing immunoblotting assays. In none of the patients, except those with SLE, was any clinical manifestation of SLE noted. The mere presence of anti-Sm antibodies of the IgG isotypes is not sufficient for the development of SLE, however, its presence is highly specific for SLE. PMID- 2261735 TI - Follow-up with OM-8980 after a double-blind study of OM-8980 and auranofin in rheumatoid arthritis. AB - A 6-month double-blind study of OM-8980 and auranofin in 145 patients with rheumatoid arthritis was followed by an open observation period of 6 months for which 100 OM-8980-treated patients could be assessed. At the end of this second phase, the Ritchie index, number of swollen joints, pain scale, morning stiffness, grip strength and ESR had all improved further with respect to the significant improvements already recorded under OM-8980 and auranofin in the double-blind phase. The statistical analysis of the Ritchie index, pain scale and ESR showed significant changes in these 3 parameters during both the 6-month follow-up phase and the entire 12-month period. As regards the tolerance, 2 patients reported gastrointestinal disorders during the follow-up. The investigators' final assessment of efficacy indicated an improvement in 76% of the patients during the follow-up phase and in 95% during the entire 12-month period. PMID- 2261736 TI - Intradiscal injection of triamcinolone hexacetonide for acute, subacute, and chronic sciatica. Results at 3 months an open-prospectus study of 30 cases and review of the literature. AB - The authors report an open study of 30 cases of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica. The patients were monitored at months 1 and 3. The results were judged to be good in 36.6% of the cases, moderate in 36.6% and poor in 26.7% of the cases. Two adverse effects were reported: 1 case of reversible urinary retention and 1 case of deficiency of the dorsiflexor muscles of the foot. The good results reported in previous series were only found in this study when the indications were restricted to certain favourable prognostic factors: duration of sciatica less than 6 months and CAT scan appearance of discal hernia. This technique has the advantage of being simple, economical and nonallergic. On the basis of the encouraging results of the initial series, this technique should be considered as an interesting therapeutic alternative in sciatica. Larger series and double-blind studies, however, are necessary to confirm the initial results. PMID- 2261737 TI - Comparison between radial bone mineral density measured by single photon absorptiometry and histomorphometric bone mass parameters measured on iliac crest biopsies. AB - Bone mineral density (BMD) measured by single photon absorptiometry (SPA) with a Moolsgard 1100 device on the distal and proximal part of the radius was compared with histomorphometric parameters measured on iliac crest biopsies in 37 patients suffering from various bone disorders. In the whole population, a good correlation was observed between the cancellous bone volume (Cn-BV/TV) measured on iliac crest biopsies and BMD from both the proximal part of the radius (r = 0.76, p less than 0.001) and the distal part of the radius (r = 0.73, p less than 0.001). Significant, although weaker correlations, were also found between the cortical width and the BMD from the distal part (r = 0.37, p less than 0.001) and the proximal part (r = 0.44, p less than 0.001) of the radius. In the 14 untreated osteoporotic patients, only a significant Spearman correlation was observed between the iliac Cn-BV/TV and the proximal radial BMD (r' = 0.69, p less than 0.05). It is thus not clear, whether radial proximal BMD correctly indicates cortical bone density in osteoporotic patients or not. The large internal variability of each of the two investigated methods and the small group of osteoporotic patients might explain the lack of correlation between the two methods in this group. PMID- 2261738 TI - Study of the effect of a glycosaminoglycan-peptide complex on the degradative enzyme activities in human osteoarthritic cartilage. AB - The in vitro collagenolytic and proteoglycanasic activity from human fibrillated osteoarthritic cartilage was determined using labelled proteoglycans and type II collagen as substrates. In vitro, a glycosaminoglycan-peptide complex (GP-C Rumalon) induced a dose-dependent inhibition of both collagenolytic and proteoglycanasic activities while sodium salicylate and indomethacin had only a weak suppressive effect on proteoglycanase. Phospholipase A2 activity was unmodified by GP-C suggesting that the effect of the drug on degradative enzymes was unrelated to prostaglandin formation. PMID- 2261739 TI - Chemoattractant production by synovial fluid cells in chronic arthritis. A study with a new double-chamber method for quantitating the motility of mononuclear cells labelled with chromium-51. AB - A new method was developed to study the migration of lymphocytes under in vitro conditions. Attractant fluid was added to the appropriate lower wells, which were filled to the brim. Peripheral blood mononuclear cells were labelled with 51Cr and then put into the upper wells. Surface tension and capillary force are enough to make clamping of these plates possible, separated by a polycarbonate filter, 15 microns thick with a pore size of 8 microns, between these two standard multiwell microculture plates. After three hours of incubation at +37 degrees C in a humidified 5% CO2 atmosphere, the migrated cells were harvested from the lower wells using a semiautomatic harvester, and the radioactivity was counted. The present method makes it unnecessary to enrich or select for different cell subsets for migration studies. Instead, density gradient separated mononuclear cells as such can be used to assess their migratory capacity. PMID- 2261740 TI - Erythema nodosum and Hodgkin's disease. AB - Erythema nodosum is an unusual manifestation of Hodgkin's lymphoma. One patient with long remission of Hodgkin's disease manifested persistent erythema nodosum beginning one and three months before relapse was clinically evident. So, the diagnosis of Hodgkin's disease should be considered in patients with unexplained recurrent erythema nodosum. PMID- 2261741 TI - Acquired Brown's syndrome in systemic lupus erythematosus: another ocular manifestation. AB - Tenosynovitis in rheumatic disorders may affect ocular muscles producing symptoms unfamiliar to rheumatologists. We present a case of superior oblique tenosynovitis (Brown's syndrome) as an early rheumatic manifestation in a patient with systemic lupus erythematosus. PMID- 2261742 TI - Organ specific and multisystemic autoimmune disease: part of a spectrum which may coexist in the same patient. AB - Five patients are described who were found to have both systemic lupus erythematosus and autoimmune thyroid disease. The coexistence of nonorgan specific and organ specific autoimmune disease is discussed. PMID- 2261743 TI - 1,25-Dihydroxyvitamin D-related hypercalcemia in lymphoma: two case reports. AB - We report two patients with non-Hodgkin's lymphoma in whom hypercalcemia and elevated 1,25 dihydroxyvitamin D (1,25-(OH)2D3) levels developed in the absence of any lytic bone lesions. Hypercalcemia responded only transiently to glucocorticoids which were ill tolerated. Intravenous APD administration was needed to circumvene hypercalcemia. Humoral hypercalcemia of malignancy is discussed. Our cases confirm that hypercalcemia associated with elevated 1,25 (OH)2D3 may occur in malignant lymphoma. PMID- 2261744 TI - Salmonella enteritidis causing joint sepsis. AB - A 22-year-old male taking dexamethasone following resection of a medulloblastoma developed an acutely painful swollen knee from which salmonella enteritidis was cultured. He had no gastrointestinal symptoms; one stool culture was positive. Active metalloproteinases without inhibitors were detected in the synovial fluid, a characteristic finding in septic joints. S. enteritidis infecting joints is extremely rare despite being the second most frequent salmonella species after S. typhimurium causing infections in man. The recent findings of S. enteritidis in eggs, and poultry points to one more source of infection. Immunosuppression is likely to facilitate infection. PMID- 2261745 TI - Spinal lesions simulating hip joint disorders. AB - In three patients pain in the groin and thigh which was initially attributed to either a malfunctioning hip prosthesis or osteoarthritic hip, was shown to arise in the spine. All patients had positive myelograms and one had electromyographic evidence of nerve root compression. Referred pain from the spine must always be considered in the differential diagnosis of pain thought to be arising from a hip replacement. PMID- 2261746 TI - Severe hypophosphataemia in a patient with Paget's disease of bone: paraneoplastic osteomalacia? PMID- 2261747 TI - Healing of articular erosions after ceasing to use suspected immunological adjuvants. PMID- 2261748 TI - Pain thresholds in rheumatic diseases. PMID- 2261749 TI - A computer program for the statistical analysis of cancer inhibition/promotion experiments. AB - The computer program discussed and presented in this paper is designed for the statistical analysis of data from cancer inhibition/promotion experiments that involve Type I censoring. The theoretical derivation of the method is described in Biometrics 43 (1987) 525-534 and Appl. Math. Lett. 1 (1988) 197-201. Turbo Pascal is used to compute maximum likelihood estimates of the parameters of interest: the mean number of induced tumors per animal, and the mean time to tumor detection. The program conducts a likelihood ratio test to determine if there is an overall experiment effect, and allows the user to select options to isolate the pair(s) of groups contributing to the experiments effect, to isolate group differences in terms of tumor number and growth rate, and to graph 95% confidence regions for the vector parameter of interest. PMID- 2261750 TI - A BASIC program for the numerical solution of the transient kinetics of complex biochemical models. AB - A highly optimized software for the kinetic analysis of complex chemical models is presented. The program is applied to the analysis of a vectorial biochemical reaction, where many species are linked by multiple equilibria of any order. The reaction stimulates the Ca2(+)-transport-linked ATPase reaction taking place in a suspension of vesicular fragments of isolated sarcoplasmic reticulum membranes, as described in many experimental reports. The model includes 12 reactants and intermediate chemical species, 14 kinetic constants, compartmentalization, and thermodynamic adjustment. The concentrations of all the model components, at any time, starting from a known initial condition, are calculated. The transient concentrations of the species are obtained by numerical integration of the appropriate differential equations, using an optimized version of the Runge-Kutta Gill algorithm, with the aid of a Digital PDP11/23 computer and a standard BASIC 11 software, which could be fast and easily fitted to work with any microcomputer and/or alternative language or faster working compiled BASIC version. The errors of the calculations are evaluated. PMID- 2261751 TI - Dental diagnosis and treatment (DDx & Tx): interactive videodisc patient simulations for dental education. AB - Judgement skills and critical thinking in dentistry are developed through: (1) a systematic approach to gathering and processing information, and (2) an essential amount of practical experience. A new system of interactive videodisc patient simulations titled 'Dental Diagnosis and Treatment' or 'DDx & Tx' has been developed to provide students or practicing dentists an opportunity to develop and practice their critical thinking skills. The DDx & Tx system consists of patient simulation software, a laser-reflective videodisc with its accompanying database, a patient simulation management system, and documentation. An authoring tool is under development. Faculty-authored simulations require students to gather information, formulate diagnoses, order appropriate treatments and properly sequence those treatments. The students' performance is automatically scored and a critique is provided as a review. PMID- 2261752 TI - A computer model of the heart that obeys Starling's law. AB - We developed a computer model of the heart that accurately reproduces human left ventricular pressure wave morphology. The model factors beat-to-beat venous return in generating cardiac output and simulates congestive heart failure when the venous return exceeds the heart's pumping capacity. The blood pressure waveform produced by our model resembles experimental data with a greater than 98% correlation and the model incorporates Starling's transfer function. The model is useful for simulations of cardiovascular hemodynamics where accurate waveforms and venous return feedback or modeling failing hearts are important. PMID- 2261753 TI - A computer program for calculating kappa: application to interexaminer agreement in periodontal research. AB - The kappa statistic is a frequently used measure of interobserver agreement when two or more observers are asked to rate the same items or subjects on some criterion. The advantage of the kappa statistic over simple agreement is that it corrects for agreement by chance. In dental research, because multiple examiners may be involved in assessing subject variables such as attachment loss, bleeding on probing, or periodontal pocket depth, some statistical measure of agreement is needed. The program described here was developed for estimating agreement among periodontal examiners, but also could be used in clinical teaching applications. Assumptions and limitations of the kappa statistic are discussed. Examples of outputs illustrate applications of the program. PMID- 2261754 TI - A system of personal computer control programs for tapping experiments. AB - A system of control and measuring programs on IBM-PC or compatible computers was developed to explore the precision and accuracy of a subject's timing mechanisms in sensorimotor behavior. Various rhythmic patterns composed of several accentuated and non-accentuated tones which the subject has to follow or to reproduce by finger tapping can be designed. All parameters of the stimulus tones, i.e., duration, pitch and inter-tone pause, in a pattern are variable. Two parallel, independent responses can be monitored simultaneously as well. In this way, the mutual influence of responses of two subjects or two responses of one subject can be analyzed. The programs are written in MODULA-2, the output data are in the ASCII format and can be processed by any common statistical package. PMID- 2261755 TI - Semiautomatic method for histomorphometry. AB - A semiautomatic measurement system for histomorphometry is presented. The system is based on a steppermotor-driven scanning stage which the operator controls via a digitizer. Movement in the scanning stage is carried out with respect to stationary cross-wires in the ocular of the microscopy. The system is connected to a PC-AT computer which utilizes the x- and y-coordinates of these movements for the calculation of the morphometric measurements. In addition, the system is supplemented by software for storage and analysis of measurement data. PMID- 2261756 TI - Family structure: a general program for displaying complex pedigree data. AB - A general method for automated presentation of complex pedigree data is described. This method, called 'family structure,' allows presentation of genetic relationships for an unlimited number of individuals, and is well suited for description of both human and non-human animal populations. The method is especially useful for populations in which families are interrelated or individuals produce offspring by several mates. This method has been incorporated into a computer system for animal pedigree storage and analysis. PMID- 2261757 TI - Effects of VIP and GRF on the release of growth hormone in perifused bovine adenohypophysis. AB - The effects of vasoactive intestinal polypeptide (VIP) and growth hormone releasing factor (GRF:hpGRF(1-29)-NH2) on the release of growth hormone (GH) from anterior pituitaries from cows were examined by using an in vitro superfusion system. The pituitaries were excised randomly from cycling cows, dissected to obtain medial portions, and minced to obtain cubes with approximate dimensions of 1.5mm on a side. For each perifusion setup, 5 pieces of pituitary tissues were chambered and flushed with modified KRB solution saturated with 95% O2-5% CO2 at 38C. Perifusion with media containing 10(-6) and 10(-7)M VIP for 30 min induced a significant release of GH during the treatments (P less than 0.05). VIP (10(-8)M) increased GH levels significantly (P less than 0.05), but to a minor degree. Perfusion with the media containing 10(-6), 10(-7) and 10(-8)M GRF for 30 min markedly increased the GH concentration and the effects continued up to 90 min after termination of the perifusion of the peptide (P less than 0.05, P less than 0.01). The GH releasing effects of GRF could be seen at doses as low as 10(-11)M GRF (P less than 0.05, P less than 0.01). These findings indicate that the GH releasing effect of VIP is less potent than that of GRF in cows. PMID- 2261758 TI - Developmental patterns of plasma insulin-like growth factor-1 concentrations in sheep. AB - A study was undertaken to examine the ontogeny of circulating insulin-like growth factor-1 (IGF-1) concentrations in sheep. The trial was a balanced 2 x 2 factorial design incorporating the effects of sex and rearing rank with a total of 48 animals. Blood sampling was initiated four weeks post-weaning (about 3 months of age) and continued every 2 weeks for 6 months and then every 4 weeks for 7 months. Fecal egg counts and plasma concentrations of non-esterified fatty acids (NEFA) were also determined. IGF-1 concentration was positively related to live weight throughout the trial, even when adjusted to common sex and rearing rank. Sex of lamb had a significant effect on plasma IGF-1 concentrations with concentrations in males being greater than those in females. Puberty in females, as determined by date of first estrus, was associated with an increase in plasma IGF-1 concentrations. Although puberty in males was not measured, a surge in plasma IGF-1 concentrations around the approximate time of puberty in males resulted in a marked divergence between the sexes which remained throughout the study. Rearing rank did not influence plasma IGF-1 concentrations beyond 7 months of age. Plasma IGF-1 concentrations tended to be negatively associated with plasma NEFA concentrations and fecal egg counts but relationships were only occasionally significant. IGF-1 levels were highly repeatable, concentrations at the first sample being significantly correlated with those at all subsequent samples. Implications of these results in relation to potential use of plasma IGF 1 concentration as a genetic marker for productivity are discussed. PMID- 2261759 TI - Effects of winter nutrition and summer pasture or a feedlot diet on plasma insulin-like growth factor I (IGF-I) and the relationship between circulating concentrations of IGF-I and thyroid hormones in steers. AB - Effects of two winter nutritional levels (LOW, MOD) and two summer pastures (bahiagrass, BG; perennial peanut, PP) on plasma IGF-I, and the relationship between IGF-I and average daily gain (ADG), thyroid hormones, plasma urea, packed cell volume (PCV) and steer type were determined in 101 steers (217 kg) varying in breed composition, frame size and initial condition. Relationships between body composition or composition of gain and IGF-I were determined in 11 contemporary steers assigned directly to the feedlot. Initial IGF-I (57.9 +/- 3.5 ng/ml) was positively correlated (P less than .05) to initial condition, estimated percentage of Brahman and plasma T3, but not related to subsequent ADG. During the 126-day wintering period, ADG was .21 kg for the LOW winter treatment and .47 kg for the MOD winter treatment. Concentration of IGF-I in the wintering period was affected (P less than .01) by nutritional level (LOW = 71.8 ng/ml, MOD = 150.6 ng/ml) and was positively related to winter ADG in MOD steers (P less than .01) but not in LOW steers. Concentration of IGF-I in winter was also positively related to condition at the end of the winter period (P less than .01), T3 (P less than .05) and T4 (P less than .05). There were no effects of winter treatment on IGF-I during the subsequent summer pasture period. During the 145-d summer period, ADG was .53 kg for BG and .68 kg for PP. Concentration of IGF-I during the summer period was affected (P less than .05) by pasture treatment (BG = 138.6 ng/ml, PP = 181.9 ng/ml), was positively related (P less than .01) to PCV and percentage of Brahman, and was negatively related (P less than .05) to estimated percentage of English breeding. In steers assigned directly to the feedlot, IGF-I was correlated with empty body (EB) weight (r = .59, P less than .10), EB water (r = -.59, P less than .10) and EB protein (r = .60, P less than .10) at slaughter, and with days on feed (r = -.65, P less than .05), but was not correlated with ADG or rate of component gain. These data indicate that IGF-I is related to nutritional status in steers as in other species, that there may be significant breed or cattle type differences in circulating concentrations of IGF-I, and that circulating concentration of IGF-I may be functionally related to plasma concentration of thyroid hormones. PMID- 2261760 TI - In vitro release of progesterone and estrone by the porcine placenta throughout gestation. AB - In vitro release of progesterone (P4) and estrone (E1) by the porcine placenta was characterized at 12 days of gestation between d 20 and 110. Placental P4 rose linearly from d 25 to 40, plateaued between d 40 and 50, continued to increase to a peak concentration at d 100, then decreased sharply to d 110. Placental E1 decreased abruptly from d 30 to a nadir at d 40, then increased continuously from d 70 to peak values at d 110. This biphasic pattern for E1 mimicked the pattern observed in allantoic fluid and maternal plasma pools. Only trace amounts of testosterone (T) were measured at d 20, 50, 60, and 100, suggesting rapid aromatization of C19 steroids to estrogens. The results of this in vitro study indicate that the porcine placenta collected throughout gestation can release large quantities of P4, although the lack of an increase in systemic P4 suggests that under in vivo conditions P4 is utilized and/or metabolized within the uterus. PMID- 2261761 TI - Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats. AB - Absorption kinetics of regular, isophane (NPH), and protamine zinc (PZI) insulin were evaluated in seven clinically normal domestic shorthair cats by measurement of serial serum concentrations of insulin after subcutaneous administration of each insulin preparation. These results were compared to measurements of serial serum insulin concentrations after similar dosages of regular insulin were administered intravenously. Regular insulin administered subcutaneously was better absorbed than NPH and PZI insulins (mean bioavailability index 45.4% vs. 33.0% for NPH and 27.3% for PZI), and resulted in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (3529 pM vs. 1044 pM for NPH and 344 pM for PZI, P less than 0.05). The mean time interval between insulin administration and time to reach peak concentrations was significantly shorter for regular insulin than for NPH or PZI insulin (0.5 hr vs. 1.6 hr for NPH and 4.1 hr for PZI, P less than 0.05). There was also a significant difference (P less than 0.05) in the mean time interval between insulin injection and return of serum insulin concentrations to baseline values between regular insulin (5.6 hr) and NPH (7.7 hr) or PZI (13.1 hr) insulins. When compared with PZI, NPH insulin showed a significantly (P less than 0.05) greater maximal increase in mean serum insulin concentrations over baseline values. In addition, the interval between insulin administration and time to reach peak concentrations, as well as the time between insulin injection and return of serum insulin concentrations to baseline values, were also significantly shorter with NPH insulin than with PZI. These results suggest that NPH and PZI insulins administered subcutaneously to cats may require a short time to reach peak serum insulin concentrations as well as a relatively short time for circulating insulin concentrations to return to baseline values. If the absorption kinetics are similar to that in this study, most cats with diabetes mellitus would need twice daily injection of NPH or PZI insulin to adequately control the diabetic state. PMID- 2261762 TI - Uterine secretions of the cow contain proteins that are immunochemically related to the major progesterone-induced proteins of the sheep uterus. AB - Proteins that cross-react with antiserum to the major progesterone-induced proteins found in the pregnant sheep uterus, the uterine milk proteins (UTM proteins), were detected as radiolabelled secretory products of endometrium from pregnant cows. Cross-reactive proteins included a form at 57,000 molecular weight as well as other lower-molecular-weight variants found in lower amounts. Similar proteins were also detected in uterine fluid from a cow at day 270 of gestation. Using immunohistochemical procedures, proteins that cross-reacted with antiserum to sheep UTM-proteins could be localized to the epithelial cells of endometrial glands in the cow. Results indicate that UTM-protein-like molecules are secreted by the endometrium of the cow during pregnancy. PMID- 2261763 TI - Purification and partial characterization of growth hormone from the dromedary (Camelus dromedarius). AB - Camel growth hormone (camGH) was isolated from the insoluble residue left after extraction of the gonadotropins FSH and LH from a single batch of one-humped camel (Camelus dromedarius) pituitaries. Only one form of camGH was isolated and characterized; no glycosylated form of camGH could be evidenced. The isoelectric points (pI) of camGH was determined by chromatofocusing. The N-terminal amino acid sequences of camGH was determined and compared to those of GHs from other species. The availability of this hormone and our better knowledge of its structure will permit to undertake the study of its structure-function relationships and of its physiological functions in this economically important species. PMID- 2261764 TI - Effects of the dam on equine chorionic gonadotropin concentrations during pregnancy. AB - Breeding trials were designed to determine the influence of the mare on serum concentrations of equine chorionic gonadotropin (eCG) from Day 39 to Day 104 of gestation. Sires were ranked according to mean eCG concentrations found in the groups of randomly selected mares to which they were mated in 1983. Mares were ranked according to their mean eCG concentrations on Days 55, 71 and 85 of gestation (Day 0 = mating), in 1983 and 1985. In the 1986 breeding season, mares that had pregnancies characterized by high eCG levels were mated to sires previously associated with low eCG concentration pregnancies and low producing mares were mated to sires associated with high eCG concentration pregnancies. The highest eCG concentrations (12.8 micrograms/ml serum) were detected on Day 55 of gestation in mares mated to the low-ranked sire (P less than 0.01), indicating an influence of the mare on serum eCG concentration. A comparison of eCG production by individual mares in 1985, 1986 and 1987 showed that mares retained the same rank (P less than 0.001), regardless of the rank of the sire to which they were mated. It was concluded that the influence of the mare predominates in determining eCG concentration. In 1987, the highest ranked sire was mated to the highest eCG producing mares (ranked 1-20) and the second highest ranked sire was mated to mares ranked 21-40. Two distinct subgroups resulted, suggesting that the selection of sires and mares could be used to maximize the production of eCG. PMID- 2261766 TI - Bronchial hyperresponsiveness in asthma: its significance and therapy. PMID- 2261765 TI - Effects of dietary T3 on growth parameters and hormone levels in normal and sex linked dwarf chickens. AB - Tri-iodothyronine (T3) has been administered in the diet, from day of hatch until 8 weeks of age, to sex-linked dwarf and normal chicks of both sexes from a brown egg slow-growing strain. Feed was supplemented with either 0.1 ppm or 0.5 ppm T3. A significant genotype by treatment interaction was observed on body weight: the effect of T3 in males was significantly positive for dwarfs and null for normals, the effect in females was null for dwarfs and significantly negative for normals. Feed efficiency was rather decreased by the treatment in both genotypes. Abdominal fatness was decreased in a dose-dependent manner in both genotypes, while rectal temperature was raised in dwarf chicks only. Plasma T3 was raised to normal levels in dwarfs receiving 0.1 ppm exogenous T3, while the 0.5 ppm dose yielded hyperthyroid levels. Plasma GH levels were decreased in a dose-dependent manner by the T3 treatment, the effect being larger in dwarfs. Surprisingly, plasma IGF-I was unchanged in spite of the GH decrease, whatever the genotype or the sex. It was concluded that exogenous T3 alone can have a stimulatory effect on growth in dwarfs but can not fully restore a normal growth rate. Both T3 and IGF-I are important for a normal growth and the relationship between T3 and IGF-I production should be further investigated in order to better understand the physiological modifications due to the sex-linked dwarf gene. PMID- 2261767 TI - Black-white disparities in health care. AMA Council on Ethical and Judicial Affairs. AB - Persistent, and sometimes substantial, differences continue to exist in the quality of health among Americans. Blacks have higher infant mortality rates and shorter life expectancies than whites. Underlying the disparities in the quality of health among Americans are differences in both need and access. Moreover, recent studies have suggested that even when blacks gain access to the health care system, they are less likely than whites to receive certain surgical or other therapies. These studies have examined treatments in several areas, including cardiology and cardiac surgery, kidney transplantation, general internal medicine, and obstetrics. Whether the disparities in treatment decisions are caused by differences in income and education, sociocultural factors, or failures by the medical profession, they are unjustifiable and must be eliminated. In this report, the Council on Ethical and Judicial Affairs of the American Medical Association emphasizes the need for (1) greater access to necessary health care or black Americans, (2) greater awareness among physicians of existing and potential disparities in treatment, and (3) the continued development of practice parameters, including criteria that would preclude or diminish racial disparities in health care decisions. PMID- 2261768 TI - Healthnet: Connecticut Consumer Health Information Network. PMID- 2261769 TI - Adenosine. PMID- 2261770 TI - Cut and sew. PMID- 2261771 TI - Poverty--the most deadly and prevalent of all diseases. PMID- 2261772 TI - The tragic case of Nancy Cruzan. PMID- 2261773 TI - A method for preparation of renal tubular basement membrane. AB - A method is presented for the preparation of tubular basement membrane from renal cortex. The procedure utilizes a Polytron tissue disrupter, differential sieving, and for some species, sucrose density centrifugation. The procedure is especially useful for obtaining highly purified rabbit and bovine tubular basement membranes. Human tubular and glomerular basement membranes can be prepared with some cross contamination. The method offers the capability of rapidly generating large quantities of the basement membranes that retain the Goodpasture antigen and a TBM antigen associated with anti-TBM nephritis. PMID- 2261774 TI - Quantitation of elastin in tissues and culture: problems related to the accurate measurement of small amounts of elastin with special emphasis on the rat. AB - Both rat and sheep elastin can be quantified by measurement of discrete peptides released from the insoluble protein by thermolysin digestion. These peptides are easily visualized and measured by HPLC. With the sheep the tallest peak on the chromatogram represents the VGVPG pentapeptide derived from a repeating sequence seen in elastin from many species. This repeating sequence allows for amplification of the signal significantly above background so that accurate quantitation can be carried out. The measurement is reproducible over a wide range of protein concentrations. With the rat however the pentapeptide is not present but appears to be replaced by other repeating sequences. We quantitated and determined amino acid sequence on 8 peaks present in the early portion of the chromatogram for purposes of quantifying rat elastin. That signal most reliably present over a range of concentrations was tyrosyl-glycine (YG) which eluted at 8.5 minutes. We have used YG as a basis for quantitation of rat elastin both from tissues and tissue culture. We have also shown that the desmosine crosslinks are not constant in elastin produced in a neonatal rat smooth muscle culture system but vary with the age of the culture. We thus propose that an index of maturation be considered for a given elastin in the form of mumoles of crosslink per gram of elastin so as to better define its quality. PMID- 2261775 TI - Glycosaminoglycan involved in the cation-induced change of body wall structure of sea cucumber Stichopus japonicus. AB - The body wall of sea cucumber Stichopus japonicus was treated with various concentrations of several cations, and examined for changes in toughness, taking punch force as parameter. Toughness of the body wall tended to decrease with increasing concentration of each cation, but in different modes depending mainly upon the valency of cation: e.g., the body wall completely lost toughness in 0.3 M Na+ or 0.4 M K+, whereas it retained more than half the initial toughness even in 0.4 M Ca2+ or Mg2+. Glycosaminoglycan (GAG) from the body wall was dissolved in water, and examined for viscosity changes as caused by those cations. Specific viscosity (eta sp) decreased from 0.71 (without cation) to 0.47-0.57 in the presence of 0.1 M monovalent and divalent cations. At 0.4 M, monovalent cations reduced eta sp to 0.38-0.46, but divalent cations increased eta sp to 0.56-0.63. Electron microscopy demonstrated that GAG matrix was clearly observed in the absence of cation, but disappeared in 0.4 M NaCl, forming wide free spaces in the body wall. These results all suggested that GAG is closely involved in the change of toughness of sea cucumber body wall. PMID- 2261776 TI - Water transport in extracellular matrices. PMID- 2261777 TI - Updating on continuous ambulatory peritoneal dialysis. PMID- 2261778 TI - Anatomy and physiology of the peritoneal membrane. PMID- 2261779 TI - Osmotic agents in the peritoneal fluid. PMID- 2261780 TI - Nutrition and metabolism in continuous ambulatory peritoneal dialysis. PMID- 2261781 TI - Peritoneal dialysis improves uremic endocrine disorders. PMID- 2261782 TI - Cardiovascular system in continuous ambulatory peritoneal dialysis. PMID- 2261783 TI - Continuous ambulatory peritoneal dialysis in diabetic patients. PMID- 2261784 TI - Continuous cyclic peritoneal dialysis. PMID- 2261785 TI - Continuous ambulatory peritoneal dialysis: present status and future trends. PMID- 2261786 TI - Management of facial irritation due to cosmetics in patients with "status cosmeticus" (cosmetic intolerance). PMID- 2261787 TI - Recent developments in sexually transmitted diseases: is Kaposi's sarcoma a sexually transmitted disease? PMID- 2261788 TI - New developments in our understanding of the biology of psoriasis. AB - Increased keratinocyte proliferation and inflammation are two hallmarks of psoriasis. In this paper new developments in skin biology and biochemistry that help us to understand these two features of the disease are discussed. Methods to control proliferation and inflammation based on these scientific developments are presented. PMID- 2261789 TI - The role of psychoneuroimmunology in the pathogenesis of psoriasis. AB - Although it is well known that stress can trigger and exacerbate psoriasis, the exact mechanism is unknown. An explanation is presented based on recent findings in psychoneuroimmunology. The number of cutaneous sensory nerves known to release neuropeptides, such as substance P, is increased in patients with psoriasis. Preliminary data indicate altered concentrations in psoriatic lesions of the same neuropeptides known to be altered in the brain during stress. An anatomical pathway is suggested to explain how descending information from the brain could cause release of neuropeptides in the skin, which would then induce psoriasis. Biochemical and clinical evidence is presented to support the relationship between stress and psoriasis. PMID- 2261790 TI - Stress and psoriasis. AB - Since most clinicians and researchers agree that stress affects the course of psoriasis, consideration should be given to advocating adjunctive therapies aimed at reducing psychophysiological stress. Biofeedback training, psychotherapy, and hypnosis are examples of adjuncts to traditional medical treatment that can reduce stress levels and have been shown to have a positive effect on the course of psoriasis. PMID- 2261791 TI - Psoriasis and arthritis. AB - The exact association between psoriasis and arthritis remains an enigma. Some investigators consider that the two disorders constitute a disease entity, psoriatic arthritis, while others support the thesis that psoriasis and arthritis are common diseases and occur simultaneously by chance. The author upholds the latter view as viable. To underscore his viewpoint he presents a comprehensive overview of the controversial opinions through an historical perspective as well as reporting on his epidemiologic and clinical findings from large population studies in the Netherlands. Therapeutic regimens for the management of both skin and joint problems are presented. PMID- 2261792 TI - Practical aspects of anthralin therapy. AB - Anthralin is an extremely effective, nontoxic treatment for psoriasis. It has not achieved the popularity in the United States that it has in Britain and Europe. The various treatment methods, including the traditional Ingram regimen and short contact therapy, are discussed. PMID- 2261793 TI - Patients' knowledge of psoriasis: pilot study. AB - A brief questionnaire was constructed to sample patients' factual knowledge of the nature of psoriasis. The study demonstrated that many patients with psoriasis have gaps in their knowledge of the disease or misconceptions that could be obstacles to effective treatment and disease prevention. The results of the questionnaire study are discussed as well as the need for patients to be aware of factors to improve self-care and extrinsic conditions that can exacerbate this disease. PMID- 2261794 TI - If you would enjoy your practice.... AB - A mechanical or routinized approach to the care of patients is dulling to the physician and may foster burnout. The original goals of most physicians- continued learning and the helping of others--are more likely to be achieved if a process of active listening is included in their therapeutic armamentarium. PMID- 2261795 TI - First and five. PMID- 2261796 TI - Denmark: the dimethylglyoxime test and international nickel dermatitis. PMID- 2261797 TI - Histamine poisoning. PMID- 2261798 TI - Portrait of a practice. PMID- 2261799 TI - Porokeratosis of Mibelli with underlying hemangioma treated by the flashlamp pumped pulsed dye laser. AB - Porokeratosis of Mibelli is a disorder of epidermal proliferation in which an abnormal clone of cells expands in a centrifugal manner. We present a case of porokeratosis of Mibelli with an underlying hemangioma that was treated with a 585 nm flashlamp-pumped pulsed dye laser. The underlying hemangioma responded well to laser therapy while the porokeratosis remained unchanged. The implications of this for the pathogenesis of porokeratosis and the specificity of the pulsed dye laser are discussed. PMID- 2261800 TI - Basal cell carcinoma: excision with immediate intraoperative tissue expansion. AB - Tissue expansion in dermatologic surgery has gained wide acceptance. We report the case of a patient with basal cell carcinoma in whom a Foley catheter was used for immediate intraoperative tissue expansion. Wound tension was decreased significantly and primary closure obtained. This technique is appropriate for office surgical procedures and provides an alternative approach to wound closure with flaps and grafts. The Foley catheter is an inexpensive and disposable tissue expander. PMID- 2261801 TI - Chronic urticaria: a model questionnaire for patient screening. AB - Evaluating patients with chronic urticaria is frequently a time-consuming, costly, and frustrating undertaking. Taking a thorough, detailed history should always be the first step in the diagnostic process as associations that may not be apparent to the patient are important to the physician. We developed a questionnaire to be used as an initial historical database in evaluating chronic urticaria and to help efficiently establish the diagnosis of underlying causes. PMID- 2261802 TI - Discoid lupus erythematosus exacerbated by contact dermatitis. AB - A patient with a nickel contact dermatitis also had discoid lupus erythematosus. The dermatitis acted as a Koebner-like reaction on the cutaneous lupus, which in turn caused progressive destruction of the earlobes. PMID- 2261803 TI - Pachyonychia congenita: a four generation pedigree. AB - Pachyonychia congenita is a rare genodermatosis characterized by symmetrical thickening and discoloration of the nails with a wedge-shaped, pinched-up, or claw-like appearance. Subungual hyperkeratosis results in a lifting up of the free edge of the nail. Nail changes may be seen alone or in combination with a variety of other cutaneous findings. The authors present a kindred with fifteen cases of pachyonychia congenita in four generations, in Lebanon County, Pennsylvania. PMID- 2261804 TI - Boils complicating scabies. PMID- 2261805 TI - Prosecution to enhance treatment. PMID- 2261806 TI - The dilemmas of childhood HIV infection. PMID- 2261807 TI - Prenatal substance abuse. AB - Beginning in the middle of the 1980s, there was an alarming rise in the number of drug-exposed newborns that was directly attributable to the rise in the abuse of cocaine and its highly addictive smokeable derivative, known as crack, by pregnant women. "Crack babies" have now become a major national problem. PMID- 2261808 TI - Interagency intervention with perinatal substance abuse. PMID- 2261809 TI - Perinatal substance abuse and public health nursing intervention. PMID- 2261810 TI - A coordinated public health and child welfare response to perinatal substance abuse. PMID- 2261811 TI - [A cross-sectional study of health status and the development of their offspring among woman workers exposed to hazards at factories in Dalian]. AB - A cross-sectional study of health status and the development of their offspring among 3,555 woman workers exposed to a variety of hazardous factors at 14 factories was conducted in 1988 in Dalian. 2,054 woman workers who were not exposed to any kind of the Hazards were used as control group. The relative risk (RR) and the attributive risk (AR) were used to compare the incidence of the study group with that of the control. There are statistically significant excesses of irregular menstruation rate, abortion rate premature and still birth rate in the study group. The rate of congenital malformations of the offsprings of women exposed to benzene is significantly high and so are women working in chemical industry, but it is not significantly different between those exposed to lead and the control group. The incidence of gynecopathy among the study group women consistently is higher than the control group indicating that the hazards in factories can adversely affect the menstruation, reproduction, and the development of their offspring of woman workers. PMID- 2261812 TI - [Effects of three kinds of inorganic dusts on lipid peroxidation of erythrocytes]. AB - This paper reports on the effects of erythrocytes when incubated with three kinds of inorganic dusts, i.e. quartz (free SiO2 content 97%), alpha-Al2O3 and TiO2. Malonaldehyde as a product of lipid peroxidation was determined as it reacted with thiobarbituric acid, and haemolytic activity was analysed spectrophotometrically. The results showed that quartz presented a stronger stimulative effect on lipid peroxidation of erythrocyte at doses of 1-8 mg than the control (P less than 0.01). No change was observed with alpha-Al2O3 and TiO2 at doses of 1-9 mg. The results suggest that the effects of dusts on lipid peroxidation of erythrocyte are similar to hemolytic reaction, directly reflecting the degree of their damage to the cell membrane. Therefore lipid peroxidation on cell membrane caused by dusts was one of the parameters of cytotoxic effects, and could be considered as one of the measures used in the assessment of cytotoxicity of dusts. PMID- 2261813 TI - [Studies on toxicokinetics of 14C-fenvalerate in animals]. AB - Using tracer technique of 14C isotope, toxicokinetics of fenvalerate was studied in rats and mice. The results strongly suggested the existence of distinct differences between species in mammals in the metabolism of 14C-fenvalerate. The absorption and elimination of 14C-fenvalerate in the blood of mice following single intragastric administration was faster than that of the rats. The plasma and brain of animal have greater affinity for 14C-fenvalerate. The absorption of fenvalerate was faster and the biological half-time was longer in brain. 14C fenvalerate and its metabolites were mainly eliminated through urine and fenvalerate can partially be stored in the skin and the hair of animal. PMID- 2261814 TI - [Radiation levels in working sites where X-ray is used for medical diagnosis]. AB - The radiation levels were measured in 109 working sites in 12 counties or municipalities of our district where X-ray was used for medical diagnosis. At the same time the effectiveness of some radioprotective facilities was assessed. The results showed that in the working sites with the ordinary protection, the average exposure rate of the surface of the worker's chest was 3.43 x 10(-8) mC/kg.s; in the sites with poor protection the average rate of exposure was the highest (about 273 x 10(-8) mC/kg.s); in the sites with other types of protection the rate was less than 10.80 x 10(-8) mC/kg.s; the exposure rate using lead chairs and aprons was 18.6 times and 5.8 times respectively lower than those without. PMID- 2261815 TI - [Preliminary study of peroxidlipid in edible oils and fats]. AB - In this article we report that peroxidlipid in edible oil-fats is extracted by using thylene glycol and measured by using TBA colorimetric method. This method is simple, rapid and has a high degree of accuracy with CV of 4.5%. The contents of peroxidlipid have been studied for certain edible oil-fats before and after high heat. The results showed that the contents of LPO were markedly increased after high heating. PMID- 2261816 TI - Immunological responses of the rabbit host to infestation by the brown ear-tick Rhipicephalus appendiculatus (Acarina:Ixodidae). AB - Rabbits developed resistance to Rhipicephalus appendiculatus instars following repetitive infestations. Rejection was accompanied by elevated IgM and IgG titres. Extracts of salivary gland, mouth-part cement and whole ticks induced a dose-related lymphocyte transformation. Skin-provocation tests with tick extracts elicited an immediate type-I hypersensitivity reaction with a delayed time-course which was influenced by antihistamines. Passive-transfer studies indicated that resistance was partially transferred with serum. A comparative histological study of the attachment sites of larvae on resistant and naive hosts demonstrated the role of eosinophils and macrophages during the initial phase of infestation. Possible rejection mechanisms are discussed in the light of these and other findings. PMID- 2261817 TI - Gross morphological changes in the salivary glands of Ixodes ricinus (Acari, Ixodidae) between bloodmeals in relation to active uptake of atmospheric water vapour. AB - The gross morphological changes in the salivary glands of Ixodes ricinus (L.) were investigated at the light microscopic level in various phases off the host with emphasis on the engorged nymph, in order to relate the capability of active vapour uptake in the course of postembryonal development to degeneration and regeneration of salivary-gland alveoli. Agranular alveoli in engorged immatures of I. ricinus, from detachment to the following early pharate phase, do not appear different from those of the unfed instars. This is also true for the female up to approximately the end of oviposition. During moulting, the agranular alveoli of the immatures degenerate and new ones are formed which are apparently already functional in teneral nymphs and adults. In contrast, granular alveoli, much enlarged in freshly detached immature I. ricinus, shrivel in the early post repletion period and soon reach a highly reduced state which is maintained until apolysis. Subsequently, they disintegrate completely. The finding that engorged and detached immatures of I. ricinus with markedly atrophied granular alveoli are capable of active vapour uptake until some days after initiation of apolysis suggests that only agranular alveoli are responsible for producing the primary secretion involved in vapour uptake. PMID- 2261818 TI - Population growth rates for Amblyomma americanum (Acari: Ixodidae) on Bos indicus, B. taurus and B. indicus x B. taurus cattle. AB - Densities of Amblyomma americanum (L.) on Bos indicus, B. taurus and B. indicus X B. taurus cattle are compared over a 3-year period, and the growth rate (rate of increase or decrease) of parasitic tick populations on each cattle genotype is estimated. Average log10 densities of parasitic A. americanum larvae are significantly (P = 0.05) lower on B. indicus cattle than on B. taurus and B. indicus XB. taurus cattle. Average log densities of nymphal and adult ticks on B. taurus cattle are significantly higher than on B. indicus cattle but neither cattle genotype differs in this regard from B. indicus X B. taurus cattle. Estimated annual tick population growth rates (log10) for parasitic A. americanum are positive on B. taurus cattle (+0.84 larvae, +0.09 nymphs, +0.22 adults calf-1 year-1), but are negative on B. indicus (-0.18 nymphs, -0.14 adults calf-1 year 1) and B. indicus X B. taurus cattle (-0.45 larvae, -0.24 nymphs, -0.14 adults calf-1 year-1). Populations of parasitic larvae were not detected on B. indicus cattle. PMID- 2261819 TI - Scototaxis and target perception in the camel tick Hyalomma dromedarii. AB - The camel tick, Hyalomma dromedarii, exhibited positive scototaxis in an arena, e.g. it oriented towards a black or grey target in front of a white background. The degree of the scototactic response varied with the size and the elevation of the target, with its luminance contrast, with its shape and with the speed by which the target was moved: (1) the response to stationary and moving targets increased with increasing target size; (2) presentation of the targets at an elevation of 11 degrees--15 degrees induced the highest response; (3) the response decreased with decreasing luminance contrast of the target; (4) targets with the shape of a disk, a triangle standing on a vertex, a vertical bar or a silhouette of a dromedary caused high responses; a low response was observed when the target was a horizontal bar and there was no response to a striped pattern; (5) the smaller the size of a disk, the faster it had to be moved to elicit an optimum response. The smallest disk which elicited a significant response appeared under a visual angle of 4.8 degrees for a thick at the starting point. The smallest dromedary-shaped silhouette which elicited a significant response corresponded to the silhouette of a real dromedary at a distance of 18 m. PMID- 2261820 TI - Hemocytic encapsulation of implants in the tick Dermacentor variabilis. AB - Implants of Epon, inserted in Dermacentor variabilis (Say) through incisions in the cuticle, were encapsulated by hemocytes. We followed this process at intervals of 1,3,6, 12 and 24 h, and every 24 h thereafter up to 120 h. Degranulation of Type 1 granulocytes and coagulation of hemolymph were first seen at 1 h after implantation and were the earliest evidence of encapsulation. By 3 h after implantation, the degranulation and disintegration of granulocytes had formed a matrix at the Epon surface. From 6 h until encapsulation was completed, plasmatocytes and granulocytes continued to respond to degranulation and formed multiple cell layers around the Epon implant. The capsule was complete at 72 h after implantation. Completion was marked by decreasing degranulation, migration of hemocytes from the outermost layers of the capsule, and by the appearance of loosely attached hemocytes on the outer surface of the capsule. The most common junctional complex observed was gap junctions. PMID- 2261821 TI - Prevalence of diabetes and impaired glucose tolerance in elderly subjects and their association with obesity and family history of diabetes. AB - The goal of this study was to investigate the prevalence of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in elderly subjects and their association with obesity, central obesity, and a family history of diabetes. A representative population sample of 1300 subjects (471 men, 829 women) aged 65-74 yr participated in the study. The participation rate was 71%. The prevalence rates of previously and newly diagnosed NIDDM and IGT, based on a history of diabetes and an oral glucose tolerance test, were 8.7, 7.0, and 17.8% in men and 11.7, 7.1, and 19.1% in women. Thus, 33.8% of men and 37.9% of women had abnormal glucose tolerance according to World Health Organization criteria. Obesity (body mass index greater than or equal to 27 kg/m2 in men and greater than or equal to 25 kg/m2 in women) and central obesity (waist-hip ratio greater than or equal to 0.98 in men and greater than or equal to 0.89 in women) doubled the prevalence of IGT or NIDDM. The combination of obesity and a family history of diabetes was associated with a more marked increase in the prevalence of IGT or NIDDM in men than in women. Simultaneous presence of obesity, central obesity, and a family history of diabetes was associated with a threefold increase in the prevalence of IGT or NIDDM (65.4 vs. 24.1% in men, 52.8 vs. 19.6% in women, P less than 0.001). The major risk factors for NIDDM, e.g., obesity, central fat distribution, and a family history of diabetes, explained 10% of the variance in 2-h glucose values in multiple regression analysis. In conclusion, the prevalence of IGT and NIDDM was high in elderly subjects. Although obesity, central fat distribution, and a family history of diabetes were significantly associated with the increased prevalence of IGT or NIDDM, they explained only a minor proportion of the variance in 2-h glucose values. PMID- 2261822 TI - Weight gain associated with improved glycemic control in population-based sample of subjects with type I diabetes. AB - Previous studies have suggested that weight gain is an identifiable risk of efforts to lower blood glucose with intensive insulin therapy in type I (insulin dependent) diabetic subjects. This study examined this relationship in a population-based sample of type I diabetic subjects participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Four hundred five adults (aged greater than or equal to 21 yr) with type I diabetes, who were diagnosed before age 30 yr, were studied from 1980 to 1982 and in a follow-up examination from 1984 to 1986. Weight gain over the 4-yr interval averaged 1.8 +/- 5.9 kg. Weight gain was significantly associated (r = -0.26, P less than 0.001) with improvements in glycosylated hemoglobin levels; the quartile of subjects with the greatest improvements in glycemic control gained 3.4 kg, whereas the quartile of subjects with the smallest improvements in glycemic control lost 0.6 kg. Weight gain was also correlated with increases in the number of shots of insulin per day and change in the treatment regimen from one type of insulin to a combination of short- and long-acting insulins. These results suggest that weight gain may be an adverse consequence of improved glycemic control. Efforts to better understand the mechanism explaining weight gain and to prevent weight gain are needed. PMID- 2261823 TI - Effect of captopril on glucose concentration. Possible role of augmented postprandial forearm blood flow. AB - The goal of this study was to evaluate the effects of captopril on plasma glucose concentration. The daily profiles of the plasma glucose levels were determined in 12 non-insulin-dependent diabetic normotensive subjects, treated with or without captopril at a dose of 25 mg 3 times/day. Forearm blood flow was also measured by strain-gauge plethysmography. Administration of captopril improved the daily profile of the plasma glucose level. Postprandial forearm blood flow was also augmented 2 h after a meal. These results suggest that angiotensin-converting enzyme inhibitors may improve glucose metabolism in diabetic subjects, possibly through enhancement of blood flow to skeletal muscle. PMID- 2261824 TI - Self-care predictors of metabolic control in NIDDM patients. AB - The objective of this study was to evaluate whether the relationship between self care behavior and metabolic control is comparable in patients with non-insulin dependent diabetes mellitus (NIDDM) on insulin and not on insulin. We studied 84 NIDDM patients hospitalized for an elective admission in Washington University's Model Demonstration Unit. At admission, patients reported the frequency of exercise, blood glucose monitoring, and meal skipping for the previous 2 wk. Metabolic control over the previous 8-12 wk was determined from glycosylated hemoglobin assays. In cross-sectional analysis controlling for patient sociodemographic and health characteristics, glycosylated hemoglobin levels were positively related to meal skipping (P = 0.0008) and negatively related to the frequency of blood glucose monitoring (P = 0.0025). Self-care behaviors explained 26% of the variance in glycosylated hemoglobin levels in NIDDM patients. Multivariate modeling demonstrated no significant interaction effects between insulin treatment and self-care on metabolic control. In conclusion, these findings support the clinical significance of self-care activities for metabolic control in NIDDM patients, particularly meal skipping and blood glucose monitoring. PMID- 2261825 TI - Effects of thromboxane synthesis inhibitor triflusal on renal hemodynamics in microalbuminuric diabetic patients. AB - Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5-day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B2 (TXB2), 6 ketoprostaglandin F1 alpha (PGF1 alpha), and PGE2 in nine normotensive insulin dependent diabetic patients with UAE between 30 and 103 micrograms/min. Plasma TXB2 and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01). Triflusal produced a significant reduction in both plasma TXB2 (130 +/- 39 vs. 52 +/- 32 pg/ml, P less than 0.02) and urine TXB2 (523 +/- 249 vs. 312 +/- 11 pg/min, P less than 0.02), without changes in PRA and UAE of 6-keto-PGF1 alpha and PGE2. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition. PMID- 2261826 TI - Hospital admission guidelines for diabetes mellitus. PMID- 2261827 TI - Classification of diabetes. A fresh look for the 1990s? PMID- 2261828 TI - Erythropoietin treatment for anemia in end-stage renal disease with diabetes mellitus. PMID- 2261829 TI - Hazards of inaccurate readings obtained by self-monitoring of blood glucose. PMID- 2261830 TI - Issues in use of intraclass correlation. PMID- 2261831 TI - Capillary blood glucose sampling and transmission of blood-borne infections. PMID- 2261832 TI - Influence of insulin pen injection frequency on quality of life. PMID- 2261833 TI - Insulin pens in elderly diabetic patients. PMID- 2261834 TI - Diabetes in black populations--current state of knowledge. Bethesda, Maryland, 8 9 September 1988. Proceedings. PMID- 2261835 TI - Obesity and diabetes in blacks. AB - Diabetes mellitus is more prevalent in the American Black population than in the White population. The prevalence is increasing in Blacks, and there is evidence that it is accompanied by a greater severity of diabetic complications. In addition, mortality figures are higher in Blacks, and Black women are more seriously affected than Black men. Although the reasons for this are unclear, some factors stand out as important. These include obesity, socioeconomic status, and genetics. Obesity is a severe problem in Blacks, particularly in women. Both the degree and the distribution of fat may contribute greatly to the prevalence of diabetes in Blacks. Although the prevalence of obesity is higher in the poor economic groups, multivariate analysis suggests that poverty cannot explain all of the excess obesity that occurs in the Black population. More research is needed into a possible genetic predisposition of Blacks to obesity and diabetes and into the interrelationship between the two conditions in this racial group. PMID- 2261836 TI - Theoretical and baseline considerations for diet and weight control of diabetes among blacks. AB - This article outlines theoretical considerations for diet and weight control of non-insulin-dependent diabetes mellitus (NIDDM) and identifies factors that may be of particular importance in influencing the success of diet and weight control of NIDDM in the Black population. Long-term adherence to dietary or weight control regimens requires that the patient evaluate and restructure established eating and physical activity patterns. With the use of the social action theory as a conceptual framework, this complex behavioral change task can be understood as a function of the interplay of various self-regulatory mechanisms. These mechanisms are influenced by the person's capabilities for making changes, his/her physical condition and general health status, the physical and social environmental context, and the person's material and social resources. Many of these factors may differ for Blacks and Whites in a direction that suggests a lesser potential for effective diet and weight-loss therapy among Black NIDDM patients. For example, compared with Whites, Blacks are more likely to have limited incomes, low educational attainment, ambivalence about weight control, multiple health problems, and high-fat high-sodium low-fiber diets or food preferences. However, some evidence suggests that state-of-the-art counseling approaches can be as effective for Blacks as for Whites. The challenge is to adapt the types of approaches suggested by the social action theory for culturally appropriate and cost-effective delivery in Black community health-care settings. PMID- 2261837 TI - Exercise in therapy and prevention of type II diabetes. Implications for blacks. AB - The rationale for the use of exercise in the treatment of type II (non-insulin dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it. PMID- 2261838 TI - Diabetic cardiomyopathy. AB - The purpose of this article was to review the clinical and experimental features of diabetic cardiomyopathy, with particular relevance to the Black population. One hundred thirty-seven studies were identified, of which 57 were selected as references for this article. Diabetes is associated with the development of cardiomyopathy, independent of coronary atherosclerosis. Pathological studies show myocardial hypertrophy and fibrosis; microvascular pathology is also present, but all of these pathological findings have an uncertain relationship to myocardial failure. Hemodynamic findings of both congestive and restrictive cardiomyopathy have been described. Noninvasive studies revealed abnormal systolic and diastolic function in many diabetic subjects, particularly in the presence of diabetic complications and/or hypertension. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. One year of diabetes in dogs resulted in decreased left ventricular compliance and increased interstitial connective tissue. Studies in the diabetic rat showed a marked slowing of contraction and relaxation. Chronic insulin therapy reversed the changes in the rat model. Combining hypertension with diabetes in the rat resulted in increased myocardial and coronary microvascular pathology and greater changes in isolated muscle function, electrophysiology, and contractile protein biochemistry. Many hypertensive diabetic rats died spontaneously, showing signs of congestive heart failure. Diabetic cardiomyopathy is a significant cause of heart failure in diabetic subjects and occurs more frequently in those with microvascular complications and/or hypertension. Clinical studies are needed to clarify the natural history of this disorder, focusing on the benefits of tight control of hyperglycemia and treatment of associated hypertension. Experimental studies will clarify the pathophysiology and contribute to improved therapy. The high prevalence of diabetes and hypertension in Blacks makes these considerations especially relevant to this population. PMID- 2261839 TI - Chronic diabetic complications and tissue glycosylation. Relevant concern for diabetes-prone black population. AB - A significant segment of the Black population is affected by chronic diabetes, and most of them are subjected to severe cardiovascular, renal, and neurological complications that shorten survival and diminish quality of life. One of the important pathogenetic mechanisms under intensive investigation is advanced tissue glycosylation. Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be highly active in protein cross-linking and have been implicated in tissue damage. Such protein-glucose interactions, called advanced glycosylation end products (AGEs), are processed by macrophages through a high affinity receptor. Coupling of AGE proteins to their AGE receptors results in their degradation and removal and, simultaneously, in synthesis and secretion of pluripotential cytokines such as tumor necrosis factor and interleukin 1. This suggests that AGE may act normally as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling. In chronic diabetes, however, where accelerated accumulation of tissue AGE occurs, a disturbance of this balance may lead to several pathological, lytic, and/or proliferative responses like those in the vasculopathy of diabetes. Progress has been made with the discovery of aminoguanidine HCl, an AGE inhibitor, which has prevented significant pathology in short-term diabetic animal studies. PMID- 2261840 TI - Cross-sectional analysis of renal function in black Americans with NIDDM. AB - Our objective was to define glomerular filtration rate (GFR) and renal plasma flow (RPF) in Black Americans with non-insulin-dependent diabetes mellitus (NIDDM). This was a cross-sectional study of 71 Black NIDDM patients with diagnosed diabetes duration from 1 mo to 21 yr. Hyperglycemia was regulated and stabilized before patients were entered into the study. GFR and RPF were determined by the clearance of [125I]iothalamate and 131I-labeled hippuran, respectively, with a constant-infusion technique and four urine collection periods. Hyperfiltration, as defined by a GFR of greater than 140 ml.min-1.1.73 m 2, was found in 7 of 20 patients (35%) with newly diagnosed (less than 2 yr duration) NIDDM. The percentage of patients with hyperfiltration decreased with increasing duration of diagnosed diabetes. Decreasing GFR and RPF occurred with increasing duration of diagnosed diabetes. In conclusion, renal hemodynamic changes in Black Americans with NIDDM are similar to those known to occur in White populations with IDDM. PMID- 2261841 TI - Hypertension and diabetes in blacks. AB - This article summarizes the current state of knowledge on the interrelationship between non-insulin-dependent diabetes mellitus, obesity, insulin resistance, and hypertension in our attempt to explore the pathophysiology of the high incidence of diabetes and hypertension in the Black population in the United States. A central role for hyperinsulinemia is proposed, and questions are raised that are suitable for investigative clinical trials. PMID- 2261842 TI - Risk factors for gestational diabetes in black population. AB - In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis. PMID- 2261843 TI - Diabetic retinopathy in blacks. AB - Diabetic eye disease, particularly diabetic retinopathy, is the leading cause of new cases of legal blindness in people 20-74 yr of age in the United States. The prevalence and rate of diabetes in this age-group are higher in Blacks than in Whites. The rate of blindness from diabetic eye disease is also higher in Blacks than in Whites. Severe macular edema, the most frequent cause of decreased vision in diabetic retinopathy, appears to be more common in Blacks. Risk factors for developing macular edema include poorly controlled hypertension, hyperglycemia, and duration of disease. The higher prevalence of hypertension in Blacks may contribute to the increased severity of diabetic retinopathy. Further evaluation is necessary to determine the influence of race on the severity of diabetic retinopathy. PMID- 2261844 TI - Metabolic and health complications of obesity. AB - Overnutrition manifested by obesity has emerged as a major health problem in affluent countries. In spite of increased interest in fitness, obesity is on the increase in the United States. This is particularly so among children and adolescents. Although obesity is associated with many risk factors for diseases, the mechanisms whereby it enhances disease risk are not fully understood. Such an understanding is needed to develop strategies for management of these conditions. In this report we suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or "defect" in a given system. In the absence of such underlying defects, overnutrition, or obesity, is well tolerated. One of the most common consequences of obesity is dyslipidemia, that is, elevations of very low-density lipoprotein (VLDL) triglycerides and low density lipoprotein (LDL) cholesterol and low concentrations of high-density lipoprotein (HDL) cholesterol. The major effect of overnutrition on lipoprotein metabolism is to stimulate the production of VLDL. For patients who have an underlying defect in lypolysis of VLDL triglycerides, hypertriglyceridemia will develop in the obese state. For those who have defective clearance of LDL, obesity will accentuate hypercholesterolemia. Both of these effects can be explained by overproduction of VLDL, due to obesity, combined with a genetic defect in clearance of VLDL or LDL. The mechanism whereby obesity causes a lowering of HDL cholesterol is uncertain, although it could enhance removal of HDL by an excess of adipose tissue. Another disease associated with obesity is cholesterol gallstones. The presence of obesity more than doubles the risk for gallstones. Two underlying factors increase the danger for gallstones: a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile. Overnutrition promotes the synthesis of whole-body cholesterol, and the only route for excretion of this excess cholesterol is through the biliary tree.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2261845 TI - Genetic risks and diabetic complications--another 'black hole' in biology and medicine? PMID- 2261846 TI - Implantable insulin pumps: a current look. PMID- 2261847 TI - Altered synthesis of renin in patients with insulin-dependent diabetes: plasma prorenin as a marker predicting the evolution of nephropathy. AB - Plasma active renin (PARC) and plasma total renin (PTRC) were measured in 72 patients with childhood-onset IDDM and 37 control subjects in the supine posture. The diabetic patients were divided into three groups: group A, 55 patients with normoalbuminuria; group B, 11 patients with microalbuminuria; and group C, 6 patients with overt proteinuria. The levels of PTRC were 125 +/- 51, 240 +/- 124 and 580 +/- 285 ng/l in groups A, B and C, respectively; all of which were significantly higher than 114 +/- 33 ng/l in the control subjects. On the other hand, the ratios of plasma active to total renin, ARC/TRC, were 18.1 +/- 12.5, 10.7 +/- 6.7, and 2.9 +/- 1.4% in groups A, B and C, respectively; all of which were in turn significantly lower than 24.8 +/- 8.7% in the control subjects. Among the diabetic groups, PTRC became higher and ARC/TRC became lower in conjunction with the degree of albuminuria. The acute increments of PARC and PTRC during a standing load test were subsequently observed in 7 patients of group A, 5 of group B, 4 of group C, 13 patients with non-diabetic glomerulonephritis, and 6 control subjects. The ratios of increments of PARC to that of PTRC, delta ARC/delta TRC, were 48.3 +/- 22.3, 35.1 +/- 10.4 and 8.4 +/- 8.1% in groups A, B, C, respectively; all of which were significantly lower than 84.2 +/- 48.6% in the control subjects. Patients with non-diabetic glomerulonephritis showed, to a lesser degree, low ratio of delta ARC/delta TRC (60.4 +/- 37.9%) in conjunction with higher level of PTRC (249 +/- 89 ng/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261848 TI - Clinical profile of Japanese dialysis patients with diabetic nephropathy, diagnosed as having diabetes before the age of thirty. AB - Diabetic nephropathy is the leading cause of death in young diabetic patients. There are a large number of patients with non-insulin-dependent diabetes mellitus (NIDDM) who are diagnosed before the age of 30 in Japan. We investigated 36 patients with young-onset diabetes who started dialysis between 1978 and 1987 in our hospital. Of the 36 patients, 12 (33.3%) were classified as having insulin dependent diabetes mellitus (IDDM), 22 (61.1%) had NIDDM, and 2 (5.6%) could not be classified clinically. The percentages of the different types of diabetes in our series of dialysis patients were almost identical with those in Nagai's series of 551 diabetic patients diagnosed before the age of 30 at the Diabetes Center of Tokyo Women's Medical College from 1976 to 1981. The present study showed the young-onset NIDDM in Japan was associated with almost the same incidence of end-stage diabetic nephropathy as was IDDM. However, the number of NIDDM patients diagnosed under 30 years of age was almost double that of IDDM patients. Thus, we have to pay greater attention to the development of diabetic nephropathy in young-onset NIDDM patients than has been thought necessary in the past. PMID- 2261849 TI - Glucose and insulin concentration in amniotic fluid and in maternal blood in early and in late pregnancy. AB - Glucose concentration in the amniotic fluid decreases towards the end of gestation, whereas the insulin concentration increases. The ratio between fetal (amniotic fluid) glucose to maternal glucose is reduced by about 50% at the end of pregnancy, whereas the ratio of C peptide is increased four times. The higher glucose concentration in amniotic fluid in early pregnancy could be explained by a lower fetal metabolic rate in the early stage of development and a low insulin activity of the fetus. PMID- 2261850 TI - Quantitative analysis of serum alpha 1-acid glycoprotein levels in normal and diabetic pregnancy. AB - In an attempt to clarify the mechanism of lipid metabolism during pregnancy, alpha 1-acid glycoprotein (alpha 1-AG) was analyzed in normal and diabetic pregnant women. Seventy-two determinations of serum alpha 1-AG levels were performed in 18 diabetic pregnant women and 82 determinations in 82 normal pregnant women in all three trimesters and within 14 days postpartum. Serum alpha 1-AG levels in both normal and diabetic pregnant women decreased throughout pregnancy and rapidly increased postpartum. In all gestational stages, the serum alpha 1-AG levels were lower in diabetic women than in normal women, but the differences were not significant. No significant correlation was obtained between serum alpha 1-AG and hemoglobin A1 (HbA1) in diabetic patients. On the contrary, the serum triglyceride levels increased during pregnancy and decreased postpartum in both groups of subjects. These findings suggest that serum alpha 1-AG plays an important role in the activation of lipoprotein lipase during pregnancy. PMID- 2261851 TI - Plasma glucose and insulin responses in young Papua New Guineans (aged 10-19 years). AB - A study of rural and periurban children aged 10-19 years in the Tolai population of Papua New Guinea has demonstrated a higher average plasma glucose concentration and relative hyperinsulinaemia after an oral glucose challenge in the periurban group. The findings could not be explained by differences in age or adiposity. In the rural children, plasma insulin concentration remained consistently low throughout the range of glucose tolerance, indicating a high degree of insulin sensitivity. In the periurban children there was a marked increase in plasma insulin concentration with increasing plasma glucose concentration, possibly suggesting the development of insulin resistance, or an antecedent state, and incipient glucose intolerance. In view of the potential public health implications of these findings, further ecological studies of insulin response in children and adolescents would appear warranted. These should include appropriate measures of pubertal development, which is a possible confounding factor not addressed in the present study, as well as addressing the role of nutritional factors. PMID- 2261852 TI - Urinary excretion patterns of endogenously produced alcohols in type 1 (IDDM) and type 2 (NIDDM) diabetes mellitus compared with healthy control subjects. AB - Urinary excretion patterns of various endogenously produced alcohols, such as ethanol, propanol, isobutanol, butanol, and isopentanol, were evaluated in 17 type 1 (IDDM) and 15 type 2 (NIDDM) diabetic patients, and in two different groups of healthy control subjects (n = 12, n = 8, respectively) matched for sex, age and weight. In addition to the urinary alcohol excretion determined by gas chromatography and mass-spectrometry, four cardiovascular reflex tests were performed, and the motor and sensory conduction velocities of three different peripheral nerves were measured. In the type 1 diabetic patients, urinary excretions of ethanol and propanol were significantly higher than in the control subjects (P less than 0.0001, P less than 0.00001, respectively), whereas the control subjects exhibited significantly higher urinary excretion rates of the other three alcohols (P less than 0.007, P less than 0.02 and P less than 0.002, respectively) compared with the type 1 diabetic patients. In the type 2 diabetic patients, only the urinary excretion of propanol was significantly elevated (P less than 0.002) compared with the control subjects, while the urinary excretion rates of butanol and isopentanol were significantly lower (P less than 0.02, P less than 0.05, respectively) than in the controls. Urinary alcohol excretions were not related to diabetic peripheral neuropathy in both groups studied. The clinical meaning of the urinary excretion patterns of different endogenously produced alcohols in diabetes mellitus has to be further evaluated. PMID- 2261853 TI - Insulin release and peripheral sensitivity at the oral glucose tolerance test. AB - With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies. PMID- 2261854 TI - Quantifying the extent to which random plasma glucose underestimates diabetes prevalence in the Nauruan population. AB - The extent to which random plasma glucose levels underestimate the true prevalence of diabetes has been determined in Micronesian Nauruans. In 337 individuals who were screened on the basis of their random plasma glucose levels, the age-standardised prevalence based on a cut-off of 11.1 mmol/l underestimated the population prevalence based on a complete oral glucose tolerance test by 42% in males and 63% in females. At a cut-off level of 7.8 mmol/l the true age standardised prevalence was underestimated by 16 and 38%, in males and females, respectively. The use of random plasma glucose concentrations to determine the prevalence of diabetes, as currently defined, seems inappropriate. Performing oral glucose tolerance tests on smaller representative population samples should provide more accurate data at less expense than through large-scale screening utilizing random glucose levels. PMID- 2261855 TI - Capacity to remember prescription drug changes: deficits associated with diabetes. Collaborative Study Group of the Task Force on the Medical Interview. AB - This study compared the capacity of 44 diabetes patients and 131 non-diabetic patients to remember prescription medication recommendations made during return visits to primary care clinics. Diabetes patients were 1.6-times less likely to remember all medication recommendations immediately after the visit than non diabetic patients, a discrepancy which remained significant after controlling for sociodemographic, health status and treatment differences between the two groups. The results suggest that the cognitive deficits that diabetes patients demonstrate in laboratory testing may be severe enough to diminish their ability to learn treatment recommendations made in primary care settings. Further research is needed to determine whether recall is problematic for diabetes patients in general, or primarily for those in poor metabolic control. Clinicians who treat diabetes patients need to incorporate readily implemented strategies to promote patient recall for substantial numbers of diabetes patients to benefit from pharmacological treatment. PMID- 2261856 TI - Amylin release from perfused rat pancreas in response to glucose and arginine. AB - The effects of glucose and arginine on the release of amylin from the perfused rat pancreas were studied. Amylin, or islet amyloid polypeptide, is a 37-amino acid peptide isolated from pancreatic islet amyloid of patients with non-insulin dependent diabetes mellitus (NIDDM). Glucose stimulated dose-dependently amylin release, showing a typical biphasic pattern. Additionally, 10 mM arginine in the presence of 5.5 mM glucose also stimulated amylin release. These findings suggest that amylin is a secretory protein and its release from the pancreas is regulated by glucose and other nutrients. PMID- 2261857 TI - Re: Diabetes and diet. PMID- 2261858 TI - [Color-coded Doppler sonography for phlebothrombosis]. AB - Between November 1988 and February 1990, a total of 180 patients (76 men and 104 women; mean age 59 [17-79] years), suspected of having sustained a deep-vein or pelvic thrombosis were examined by colour Doppler ultrasound, the results being compared with those obtained by conventional phlebography. For 154 phlebographically confirmed acute venous thromboses (demonstrated by colour Doppler ultrasound in 153), four older thromboses (colour Doppler ultrasound: 7), and 22 without significant venous disease (colour Doppler ultrasound: 20), the specificity for colour Doppler ultrasound was 99%, its sensitivity 94%. In 49 patients with confirmed venous thrombosis thrombolytic treatment was started with 250,000 IU urokinase, followed by 62,500 IU hourly, the results being assessed by colour Doppler ultrasound and phlebography. This gave a specificity, compared with phlebography, of 99%, and a sensitivity of 97%. These data indicate that, in the diagnosis of venous thrombosis of the legs, colour Doppler ultrasound noninvasively provides information at least as reliable as phlebography. It may even be superior to phlebography in the demonstration of residual flow in partly thrombosed veins. PMID- 2261859 TI - [Focal size and shock wave pressure: a comparison of three different physical shock wave generators]. AB - Shock-wave delivery and focal size of three different generators electrohydraulic, electromagnetic and piezoelectric--were compared. Pressure measurements were uniformly made by needle hydrophone (piezoelectric transducer). The smallest focus, 17 x 3 x 3 mm, was achieved with the piezoelectric system (50% isobars), while the focus with the electromagnetic generator was much larger (50 x 7 x 4 mm). With the electrohydraulic generator the focal size of the 60% isobars was 20 mm in the longitudinal axis. The highest pressure, 1512 bar, was achieved with the piezoelectric lithotriptor (mean shock-wave pressure in focus: electrohydraulic 1000 + 100, electromagnetic 1000 + 25, piezoelectric 1400 + 27 bar). The rapid positive pressure rise was followed by a slower pressure fall and a small negative wave. In the focal region the negative pressure wave was between 112 and 200 bar with the electrohydraulic system, 100-146 bar with the electromagnetic one, and 134 bar with the piezoelectric one. The significance of the negative wave is not clear; perhaps it contributes to the development of the cavitation effect and facilitates stone fragmentation. PMID- 2261860 TI - [Recurrent hypoglycemia in the insulin autoimmune syndrome]. AB - A 72-year-old man with recurrent hypoglycaemia was suspected of having an insulinoma. But several diagnostic methods (computed tomography; mesenteric and coeliac angiography; sella imaging) did not reveal any tumour. 72-hour hunger test did not precipitate any spontaneous hypoglycaemia. A falling insulin-glucose ratio spoke against an insulin-producing tumour. Reactive symptomatic hypoglycaemia occurred 4.5 hours after an oral glucose test. Measurement of insulin concentration demonstrated a slow but pronounced increase (3500 microU) over an already raised initial value (816 microU/ml), typical of prediabetic metabolic regulation. Demonstration of insulin autoantibodies confirmed the diagnosis of an insulin autoimmune syndrome, which has a good prognosis. The patient became free of symptoms on a regimen of frequent small, carbohydrate-poor but fat and bulk-rich meals. Hypoglycaemia recurred when the diet was not observed. PMID- 2261861 TI - [Encephalitis in Legionella bozemanii pneumonia]. AB - A 44-year-old man, a known alcoholic and heavy smoker, was hospitalized with high fever and respiratory failure which a few hours later required intubation and artificial ventilation, although the chest x-ray had been unremarkable. Later serial chest x-ray films showed intrapulmonary infiltrations, while Legionella Bozemanii was demonstrated by direct immunofluorescence. Cranial computed tomography was unremarkable, despite the onset of tetraparesis and a severe midbrain syndrome. Cerebrospinal fluid contained merely mild lymphocytic pleocytosis. However, magnetic resonance imaging revealed symmetrical demyelinization foci in the brainstem as a sign of encephalitis. The neurological deficits regressed almost completely after several weeks of antibiotic treatment and rehabilitation measures over several months. PMID- 2261862 TI - [Ambulatory 24-hour blood pressure monitoring]. PMID- 2261863 TI - [Continuous ambulatory peritoneal dialysis: determination of treatment location]. PMID- 2261864 TI - [Treatment of heart rhythm disorders]. PMID- 2261865 TI - [Disturbed endothelium-dependent blood vessel relaxation in essential hypertension]. PMID- 2261866 TI - The dynamics of epidemiology and impact on the control of diseases. PMID- 2261867 TI - Hepatitis-B virus infection in rural and urban populations of eastern Nigeria: prevalence of serological markers. AB - Hepatitis B virus markers were measured by radioimmunoassay in the sera of 804 rural and urban inhabitants and prisoners in Nigeria. Of these, 530 (66%) subjects had one or more serologic markers of HBV infection; 9.1% were HBsAg carriers, 47% had anti-HBs and 10.1% were positive for anti-HBc alone. Total HBV exposure rate, HBsAg carrier rate and previous exposure to hepatitis B virus measured by the frequency of anti-HBc alone were significantly higher in the rural population compared with the urban population (p less than 0.0001; p less than 0.03; p less than 0.01) respectively. It was observed that by the age of 40 years, 87% of the Nigerian population have at least one HBV seric marker. There was a higher incidence of HBsAg (p less than 0.0001) and anti-HBc alone (p less than 0.001) in prisoners than in any other group. HBeAg was present in 16.4% HBsAg positive individuals with no intersex difference. No positive correlation was found between the frequency of HBV markers in rural dwellers and the history of blood transfusions. These findings suggest that horizontal transmission aided by cultural or behavioural factors and clustering of carriers rather than transfusions is the main determinant of HBV prevalence in rural Nigeria. PMID- 2261868 TI - The impact of echocardiography in the diagnosis of hypertrophic cardiomyopathy. AB - The results of 1240 consecutive abnormal echocardiography (ECHO) studies performed between January 1984 and June 1988 were reviewed in order to determine the impact made by the availability of ECHO in the diagnosis and possibly understanding of hypertrophic cardiomyopathy (HCM) in Ethiopia where the condition has not yet been reported. Cardiomyopathies in general were seen in 154 patients; of whom 53 (34.4%) were found to have HCM. The male to female ratio was 3.1:1 (40 males and 13 females) and the mean age was 27.9 yrs, (range 6-80). Asymmetric septal hypertrophy involved the basal one-third of the ventricular septum in 11 (20.8%) patients, basal two-third in 15 (28.3%) and in the majority, 27 (50.9%), it involved the whole septum. Substantial degree of septal hypertrophy (greater than 30 mm), anterolateral wall involvement and severe systolic anterior motion of the mitral valve were seen most commonly among patients with whole septum hypertrophy. These were observed less frequently among patients with basal two-third and basal one-third involvement. These associations, furthermore, appear to indicate presence of obstructive HCM. It is concluded that HCM is not uncommon in Ethiopia. In a country where there are limited diagnostic facilities, ECHO could be used for the classification of HCM and for monitoring patients' response to medical treatment. A prospective study which correlates ECHO clinical finding is needed. PMID- 2261869 TI - The management of cerebral malaria in a provincial general hospital in Kenya. AB - The practice of physicians at the Nakuru Provincial General Hospital (NPGH), Kenya, when dealing with cerebral malaria is reviewed over a 4-month period. The definition, management, and outcome of patients labelled to have cerebral malaria is presented and criticism of their practice offered in a manner applicable to other rural hospitals in Kenya. PMID- 2261870 TI - Appendicectomy in Consolata Hospital, Nyeri: analysis of operative and histological findings. AB - An account is given of 348 patients with suspected appendicitis treated with appendicectomy between September 1982 and December 1988. The operative findings in 276 cases and the findings on histology in 306 appendices are presented. An "operational error" of 18.3% (normal appendices) was made. Appendicitis was diagnosed in 41.2% of the organs while in 41.0%, the only findings were the faecoliths with or without attenuation of the mucosa. There was one case each of amoebic, schistosomal and tuberculous appendicitis. The findings are analysed and compared with those from elsewhere. PMID- 2261871 TI - Histological pattern of testicular biopsies in infertile males in Ibadan, Nigeria. AB - Testicular biopsies available in the records of the Pathology Department of the University College Hospital, Ibadan were reviewed to determine the histological pattern of primary testicular failure in this environment. Of the available biopsies, 152 were found to be adequate for study. Fifty-eight cases (38.2%) had normal spermatogenetic activity. Thirty-four cases (22.4%) had extensive or marked diffuse tubular atrophy associated with peritubular hyalinization and interstitial fibrosis. It is suggested that previous inflammatory process may play a major role in the causation of primary testicular failure in the environment. PMID- 2261872 TI - Juvenile-onset diabetes mellitus in a sickle cell anaemia patient. AB - The case of a 10-year old sickle cell anaemia patient presenting with juvenile onset diabetes mellitus is reported. The possibility of sickle cell anaemia being a predisposing factor to early onset of diabetes in an individual with a positive family history of the disease is highlighted. A review of pancreatic function in sickle cell anaemia is also undertaken. PMID- 2261873 TI - Essential thrombocythaemia associated with priapism: a case report. AB - A case of priapism complicating essential thrombocythaemia in a 45-year old Nigerian gardener is described. His platelet counts ranged from 1.2-1.6 x 10(12)/L, haematocrit from 0.25-0.33 L/L and leucocytes from 23.4-30.6 x 10(9)/L. There was a splenomegaly of 5cm. He had bilateral cavernostomy but is yet to regain penile erection 3(1)-2 months after surgery. PMID- 2261874 TI - [Changes in the contents of epidermal growth factor and EGF-like polypeptides in the liver tissue of rats in N-nitrosodiethylamine-induced hepatocarcinogenesis]. AB - It has been determined that concentration of EGF-like substances in the liver of rats with N-diethylnitrosamine-induced hepatocarcinogenesis increases and reaches its maximum in tumours (50-150 ng/mg protein). In the regenerating liver the amount of these peptides does not exceed 10 ng/mg protein. High pressure gel filtration of appropriate extracts has revealed EGF-competing substances with m. w. about 20-30 kD in the liver carcinomas. The presented data confirm that registered EGF-like substances belong to TGF-alpha peptides. PMID- 2261875 TI - [Ornithine decarboxylase activity and polyamine contents in 1,2-dimethylhydrazine induced carcinogenesis of the intestines in rats]. AB - The ornithine decarboxylase (ODC) activity and concentration of polyamines have been studied in small and large intestine during 1,2-dimethylhydrazine-induced carcinogenesis in rats. Changes in the polyamine biosynthesis consisting both in enhanced ODC activity and an increase of the intracellular content of putrescine, spermidine and spermine. Process of the polyamine synthesis activation proceeds in two phases: the most expressed and similar changes in polyamine metabolism factors have been observed at early (the 1st month) and late (the 5th-6th months) stages of carcinogenesis. It is supposed that intensification of the polyamine synthesis is a typical feature of malignization in the gastrointestinal tract. PMID- 2261876 TI - [Chromosomal damage in peripheral blood lymphocytes of rats in nitrosomethylurea induced carcinogenesis]. AB - Chromosomal damages and their dynamics in blood lymphocytes of mongrel white L10 rats treated (once) intravenously with nitrosomethyl urea (NMU) at a dose of 50 mg/kg have been analyzed. A direct correlation is revealed between carcinogenesis, chromosome aberration level in somatic cells, polyploid and hyperaneuploid cell frequency 24 hs after the NMU treatment and in the precancerous period. An increase of hyperaneuploid and polyploid cells in the organism can serve as a prognostic factor of carcinogenesis. PMID- 2261877 TI - [Alterations of c-myc and c-Ha-ras-1 oncogenes in human ovarian cancer]. AB - Fourteen cases of the ovarian carcinoma (OC) were studied for alterations of c myc and c-Ha-ras-1 oncogens. Amplification of c-myc was found in four aggressive and widespread OC. An increased frequency of one of the four common alleles of c Ha-ras-1-allele A4-was determined in OC patients. Rearrangements of c-Ha-ras-1 allelic deletions and change in the allele fragment length-were found in all OC with A4 allele. In contrast, no alterations were detected in tumours without allele A4. Thus allele A4 of c-Ha-ras-1 may be viewed as a genetic marker of predisposition to OC in combination with other clinical parameters. Alterations of c-myc and c-Ha-ras-1 oncogens were observed in 8 out of 14 OC samples suggesting that the development of this type of human neoplasm is due to rearrangements of these genes. PMID- 2261878 TI - [Cytochemical analysis of polyamines in Ehrlich ascitic carcinoma cells during different phases of mitotic cycle under the effects of difluoromethylornithine]. AB - Mice bearing Ehrlich carcinoma cells received one 80 mg/kg dose of DFMO. After 20 hours the cells were extracted from the peritoneal cavity and separated by means of sedimentation of 1 g in saccharose gradient into 9 fractions depending on the mitotic cycle phase. The content of polyamines in the cells of each fraction was detected by the fluorescent method using fluorescamine. It was shown that the tumor cells during G1 phase mitotic cycle (13-15% cells blocked) and especially cells in the 1st half of S-phase (19-23% cells blocked) were most sensitive to inhibitory effect of DFMO. PMID- 2261879 TI - [Changes in clonogenic properties of bone marrow and transplantable mice tumor cells during combined use of cyclophosphane and biological response modifiers of adaptogenic origin]. AB - The clonogenic activity of tumors and blood marrow cells has been studied in experiments on CBA, BALB/C and C57B1/6 mice with the Ehrlich adenocarcinoma and Lewis lung carcinosarcoma treated with adaptogenic drugs of Rhodiola Rosea extract, a synthetic analog of Rhodiola phenol derivative, methyluracil and their combinations with cyclophosphamide. The extract and derivative are shown to protect the myelopoietic tissue from the toxic action of cyclophosphamide, retaining or increasing the suppressive effect of the latter towards clonogenic tumors cells. These data can be the reason for using the extract and derivative during the antitumor chemotherapy as biological response modifiers. PMID- 2261880 TI - [Effects of indomethacin and BCG vaccine on growth of transplanted tumors in mice]. AB - Continuous administration of indomethacin (IM) in drinking water (20 micrograms/ml) causes moderate inhibition of the growth of transplantable tumors in control mice but significantly increases the antitumor effect of BCG vaccine inoculated in combination with transplanted tumor cells. Hepatoma 29, insensitive to the vaccine becomes highly sensitivity to it under IM administration. PMID- 2261881 TI - [Antineoplastic activity of combinations of cytostatics and dextran-ferrite administered to mice with leukemia P-388]. AB - Water solutions of adriblastin, dactinomycin, rosevin, methotrexate, cisplatin, sarcolysine, rubomycin, cyclophosphamide, 5-fluorouracil or ftorafur were combined with dextran ferrite. The obtained compositions were injected i.p. to BDF1 mice 24 hours after they were inoculated with one million of murine P388 leukemic cells. Antitumor activity was fully retained for each of these agents in combination with dextran ferrite. PMID- 2261882 TI - [Heat shock proteins and proliferative activity of cultured hepatocytes after hyperthermia]. AB - Hepatocytes in cell culture have been studied for their sensitivity to mitogenic effect of the epidermal growth factor, epidermal growth factor and insulin, 10% of cattle blood serum after hyperthermia. It is established that heat shock (43 degrees C, 90 min) induces hypersensitivity of hepatocytes to the mentioned mitogens, its maximum being observed 20-24 h after hyperthermia and coinciding in time with the development of thermotolerance and intensification of protein biosynthesis after the heat shock 68, 70, 94 kD. PMID- 2261883 TI - Do joint receptors modulate the motoneuron excitability? AB - The purpose of this study was to test the effect of joint receptor afferent discharge, during rest and during small excursion movement on kinesthetic sensation and on the excitability of alpha-motoneurons in the ankle joint in normal subjects. Movement kinesthesia was tested using a specially designed test that measured the delay time between the actual and the perceived movement during slow 5 degrees/sec), passive, 20 degrees movement excursion. These data were correlated to a second kinesthetic test using a visual analog scale in which the subject compared movements of the joint being tested and the contralateral control limb joint. The excitability of alpha-motoneurons was tested using soleus H-M recruitment curve with incremented electrical stimuli to the posterior tibial nerve at the back of the knee joint. The H-reflex recovery curve was also tested using double-identical stimuli of increasing interstimulus intervals. Joint receptors were desensitized by iontophoretic application of 3 cc. of 2% xylocaine using 5 mAmp direct current for 30 min, and movement kinesthesia and H-reflexes were tested over time up to 30 min after termination of iontophoresis. Movement kinesthesia was significantly decreased (p less than 0.05) following anesthesia, and the decrease lasted during the time of the experiment. No statistically significant changes were recorded in the H-M recruitment or H-reflex recovery curves. These results indicate that joint receptor afferents may lack the spontaneous activity recorded in other receptors, such as the skin and muscles, and do not provide position sensation at the ankle joint during rest. These results also indicate that joint receptor afferents may inform the central nervous system about movement sensation in the middle range, but this information has minimal effect on the excitability of the motoneurons as measured by H reflexes. PMID- 2261884 TI - Comparisons between surface electrodes and intramuscular wire electrodes in isometric and dynamic conditions. AB - The purpose of this study was to compare EMG surface electrodes (SE) and intramuscular wire electrodes (IWE) for isometric and dynamic contractions during an occupational cervico-brachial working task (OCWT). Six normal adult male subjects were tested on two days (two conditions with three trials each). Raw EMG signals from middle deltoid, anterior deltoid and trapezius muscles were recorded by both IWE and SE for two conditions (isometric and dynamic contractions). Full wave rectified and low pass filtered EMG, and integrated EMG were processed from raw EMG signals. The statistical analysis performed on the integrated EMG was a factorial analysis model with repeated measures. Statistical results confirmed that EMG signals, from both SE and IWE, are reliable between trials on the same day. These statistical results also confirmed that SE are more reliable than IWE on day-to-day investigations. Both electrodes recorded statistically similar signals, although the coefficient of variability between electrodes was very high (STDE%; 48% and 84%, for isometric and dynamic conditions respectively). PMID- 2261885 TI - Observations of the posterior tibial nerve SEP of patients requiring extradural spinal surgery. AB - The cortical potentials evoked by posterior tibial nerve stimulation were examined in a series of 141 hospital patients requiring extradural spinal surgery. One hundred and five patients were neurologically intact, while in 36 some deficit was present. In the intact subjects, the absolute latencies of the main medium-latency peaks (N30, P40, N50, P60) were found to vary with height and age. There were no additional gender-related differences. The latencies of the deficit group were longer than those of the intact group but only marginally useful as a clinical discriminator; their amplitudes were not significantly lower than those of the intact group. A model for variations in SEP latency is suggested. PMID- 2261886 TI - Quadriceps excitability is enhanced by a conditioning tap to the Achilles tendon. AB - In an effort to more fully investigate spinal reflex pathways in humans, we measured the isometric force-time characteristics of the patellar tendon-tap reflex in ten college-age subjects. We also conditioned the tendon jerk with a tap to the contralateral Achilles tendon or the ipsilateral Achilles tendon. The results clearly demonstrated that a conditioning tap to the Achilles tendon produced a marked (greater than 200 percent) excitatory effect onto the quadriceps muscle. Also, this effect occurred sooner when the quadriceps was conditioned by an ipsilateral stimulus rather than a contralateral stimulus. It is concluded that in accord with other conditioning studies to date, the quadriceps muscle is characterized by a predominantly excitatory effect caused by a conditioning stimulus, and that this arousal is independent of the origin of the conditioning stimulus. PMID- 2261887 TI - Disintegration of the motor unit in post-polio syndrome. Part I. Electrophysiological findings in patients after poliomyelitis. AB - CN EMG and SF EMG were performed in 12 patients many years after acute poliomyelitis, without symptoms of post-polio syndrome. In 19 muscles with clinical symptoms and in 11 clinically normal muscles chronic neurogenic changes of a similar degree were observed. Fibre density was increased in both groups of muscles. In muscles with clinical symptoms complexes of single fibres with increased jitter and blocking were more frequent than in muscles without clinical manifestations. It seems that the reinnervation after acute polio is a continuing process and thus complete stabilization and integration of the motor unit cannot be achieved. PMID- 2261888 TI - Electromyographic study of the sternocleidomastoid muscle in head movements. AB - The function of the sternocleidomastoid muscle in head movements of 30 young individuals (19-28 years old, both sexes) was studied electromyographically using a TECA TE-4 electromyograph and Beckman surface electrodes. Action potentials were found in the following head movements: free heterolateral rotation; free homolateral inclination; free and counter-resistance protraction; free and counter-resistance flexion and free extension. These movements were performed with the subjects seated and in supine position. PMID- 2261889 TI - Double pattern of relationship between skin temperature, thermoregulation and sensory nerve conduction. AB - Electroneurographic and thermographic investigations were done in 32 persons. Sensory nerve conduction velocity, amplitude of sensory nerve potential, subjective and objective sensory thresholds were determined during stimulation of each finger. The maximal and minimal skin temperatures for each finger were evaluated from thermograms taken from the dorsal and palmar surface of the hand before and after standard cooling test. The measurements were done in a thermostabilised room at 19-21 degrees C effective ambient temperature. The second degree correlations between the electroneurographic and thermographic parameters were calculated. The statistical analysis revealed the presence of a double correlation pattern depending on the homoiothermic or poikilothermic thermoregulatory ability of the finger. The differentiation threshold criterion for the poikilo- and homoiothermic group assignment was the minimal rest temperature of the finger equal to 28 degrees C. The correlations in the poikilothermic fingers were very strong and much stronger than in the homoiothermic fingers. Correlations with temperatures were strong both at rest as well as after cooling. Correlations for the sensory nerve potential amplitude likewise for the objective and subjective thresholds were stronger than for the conduction velocity. Sensory nerve potential amplitude increases and subjective and objective thresholds decrease with finger temperature. The obtained results suggest that sensory nerve conduction is related not only to the actual tissue temperature but also to local thermoregulatory ability. PMID- 2261890 TI - Conduction velocity along muscle fibers in situ in healthy infants. AB - The muscle fibers of the biceps brachii were stimulated distally with low voltages by means of two monopolar needles in twenty-two infants aged 2 to 14 years. The electrical activity was recorded proximally by means of a SFEMG electrode. Conduction velocity of the muscle fibers (MFCV) in situ calculated with this method had a bimodal distribution in the youngest individuals of less than 4 years, and a Gaussian distribution in children aged 5 to 14 years. Propagation velocity along muscle fibers increases with children's age and is significantly slower than in adults, in good correlation with the shorter limb perimeter and with the significantly smaller fiber diameter found in muscle biopsies in infancy. The latency of the evoked potentials was linearly related with the distance between stimulating and recording points, and muscle activity and propagation velocities were the same before and after curarization, that is consistent with the reliability of the method in infancy. PMID- 2261891 TI - Alpha-1,4-glucosidase activity in ram seminal plasma is inversely related to serum testosterone. AB - The epididymis of adult rams is the primary source of alpha-glucosidase in seminal plasma. Two breeds of rams were selected to ascertain whether the enzyme was under androgenic control during adult life of rams. Opposite variations between serum testosterone and alpha-glucosidase were recorded over a period of 16 months in Suffolk and Finnish Landrace. In addition, the highest percentage of sperm motility was associated with a low alpha-glucosidase content of seminal plasma. Data from this study suggest that seasonal variations of testosterone in adult rams exert a negative control on the presence of alpha-glucosidase in semen. PMID- 2261892 TI - Multiforms of mammalian adenylate kinase and its monoclonal antibody against AK1. AB - An attempt has been made to determine the intracellular distribution of the multiforms of the adenylate kinase (AK) isoenzymes in mammalian tissues, to shed some light on their physiological roles, especially in energy metabolism. The adenylate kinase zymograms obtained from isoelectric focusing yielded two typical isoform patterns: (1) with a pI greater than or equal to 9 and 8.6, specific for bovine skeletal muscle, heart, aorta and brain, and (2) with a pI = 7.9 and 7.1, specific for liver and kidney. Pattern (1) was attributed to the cytosolic isoenzyme (AK1) as demonstrated by immunostaining with anti-AK1. Pattern (2) was attributed to the mitochondrial isoenzyme (AK2). These results were largely confirmed by chromatofocusing experiments. The AK1 isoenzyme was partially purified from the cytosol fraction of bovine aortic smooth muscle and had an apparent Mr of 23.5 kilodaltons. Its kinetic features are discussed from a comparative standpoint. Finally, the human serum AK1 isoform was also detected by Western blotting with a monoclonal antibody directed against crystalline porcine muscle AK1. These results are to form the basis of further studies on the 'aberrant' adenylate kinase isoenzyme from the serum of Duchenne muscular dystrophics. PMID- 2261893 TI - Inhibition of pyridoxal kinase by methylxanthines. AB - In the presence of saturating concentrations of adenosine triphosphate (ATP) and rate-limiting amounts of pyridoxal, theophylline was found to inhibit sheep brain pyridoxal kinase (EC 2.7.1.35) competitively. The apparent inhibition constant (Ki) of theophylline for pyridoxal kinase was determined as 8.7 mumol/l. Theophylline concentrations of up to 60 mumol/l did not affect pyridoxal phosphorylation in the presence of saturating amounts of pyridoxal and rate limiting concentrations of ATP. Caffeine was less potent to inhibit pyridoxal kinase (Ki = 45 mumol/l) due to the presence of a methyl group on the 7 position of the xanthine ring structure. Theobromine showed only a weak inhibition of pyridoxal kinase (Ki = 453 mumol/l). The presence of a hydroxyethyl, hydroxypropyl or dihydroxypropyl group on the N7 position of theophylline completely abolished inhibition of pyridoxal kinase. Enprofylline (3 propylxanthine), a recently described bronchodilator, was also able to inhibit pyridoxal kinase with a Ki of 256 mumol/l. PMID- 2261894 TI - Is diarrhoea a major cause of malnutrition among the under-fives in developing countries? A review of available evidence. AB - To evaluate whether, at the community level, diarrhoea is a major cause of malnutrition or inversely whether the association between diarrhoea and growth retardation can be explained by a higher susceptibility of malnourished children to diarrhoea, all recent studies examining the relationship between diarrhoea and malnutrition in the community were reviewed. It was determined, for each of these two hypotheses, to what extent four standard causality criteria were met, viz., (i) lack of temporal ambiguity, (ii) consistency of findings, (iii) strength of association and (iv) biological plausibility. That malnutrition predisposes to diarrhoea seems likely: this is supported by a series of studies which adequately fulfil the examined causality criteria and seems biologically plausible. On the other hand, it is not clear whether diarrhoea is a major cause of malnutrition. Some studies examine the effect of diarrhoea on nutritional status over short time intervals and it cannot be determined whether diarrhoea-induced growth faltering is transient or sustained. Other studies examining this effect over longer periods do not show clearly that diarrhoea precedes malnutrition. Inconsistencies between studies and lack of evidence supporting a biologically plausible mechanism also question the importance of diarrhoea as a cause of malnutrition. PMID- 2261895 TI - Absorption and retention in acute diarrhoea. AB - 15N-yeast protein absorption, nitrogen and fat retention and stool reducing substances and lactate were measured in 6 infants who had acute diarrhoea and 15 who had had severe diarrhoea for 4 d. The results were compared with those of previously reported infants, who had had diarrhoea for 8 d. The infants were fed a full cream cows' milk, soy based or low lactose formula. In all cases the losses of nitrogen and energy in stool rose as stool weight increased. In severe diarrhoea, the losses of nutrients in stool were so great that oral feeds did not provide adequate nitrogen and energy. The smallest loss of nitrogen and fat were found in infants who had had diarrhoea for 4 d and who were fed a soy based formula. PMID- 2261896 TI - Sodium, potassium, body mass, alcohol and blood pressure in three United Kingdom centres (the INTERSALT study). AB - Standardised data on blood pressure, 24 h urinary electrolyte excretion, body mass index (BMI) and alcohol intake were collected as part of the INTERSALT study in 598 men and women aged 20-59 years, selected randomly from three population groups in the United Kingdom. For the three centres combined, mean systolic blood pressure was 121.4 mm Hg and diastolic pressure 72.1 mm Hg, urinary sodium excretion 152.1 mmol/24 h, urinary potassium excretion 61.0 mmol/24 h, urinary sodium/potassium ratio 2.64 and BMI 25.2 kg/m2. Prevalence of heavy alcohol drinking in men (greater than or equal to 300 ml/week) was 27.5 per cent. Applying overall INTERSALT regression coefficients to the United Kingdom data suggested that modest changes in average sodium and potassium intakes, together with reductions in the prevalence of obesity and (in men) of heavy alcohol drinking could lead to important reductions in average population blood pressures and the prevalence of hypertension. The potential of this multifactorial approach to blood pressure control was illustrated by stratifying individuals within each of the United Kingdom centres by sodium and potassium excretion, BMI and alcohol intake. The 20 (out of 299) men considered at 'lower risk' for high blood pressure with respect to the above variables had systolic pressure lower by 11 mm Hg (P less than 0.01); for the 27 (out of 299) 'lower risk' women, systolic pressure was lower by 5 mm Hg (P = 0.06). These non-pharmacological approaches towards more favourable blood pressure levels could be accompanied by reductions in mortality from stroke and coronary heart disease. PMID- 2261897 TI - The effect of completely purine-free diet of low sodium content on purine intermediates and end-product. AB - Intake of completely purine-free foods of low sodium content increased the plasma concentrations of both hypoxanthine and inosine and the urinary excretion of hypoxanthine, while it decreased the urinary excretion of uric acid and the fractional clearance of uric acid. However, this diet affects neither nucleotides (inosine monophosphate, adenosine monophosphate, adenosine diphosphate and adenosine triphosphate) in red blood cells, enzymes (purine nucleoside phosphorylase, adenosine deaminase and hypoxanthine guanine phosphoribosyl transferase) in red blood cells nor the fractional clearance of oxypurines. These results suggest that the salvage of purines becomes more effective by limiting the conversion of hypoxanthine to xanthine and limiting the loss of uric acid during intake of completely purine-free foods of low sodium content; also that a decrease in the fractional clearance of uric acid due to completely purine-free foods of low sodium content may be an additional mechanism associated with the conservation of purines but is more likely to be a response to the low sodium diet on the renal handling of uric acid. PMID- 2261898 TI - Variability in man of the levels of some indices of nutritional status over a 60 d period on a constant diet. AB - The biological variability of the values of various biochemical indices used for the assessment of the nutritional status of man was investigated in 4 healthy male volunteers (mean age 23 years). They were given a constant diet for 60 d, with the nutrient intake at the level of the Dutch recommendations. Blood was collected twice a week and 24-h urine samples on all 60 d; furthermore, on one day blood was collected every 2 h. Two months after the 60-d constant diet period the intra-individual variability of the various indices was studied once more, this time under habitual dietary practices. The intra-individual variability of urinary excretion of the vitamins B1 and B2 turned out to be rather high (coefficient of variation (CV) ranging from 11 to 25 per cent). Despite a constant sodium intake throughout the study, the variability of urinary Na excretion was also high (mean CV 16 per cent); the level of CV did not improve when the excretion was expressed on the basis of creatinine. Levels of serum HDL- and total cholesterol were fairly constant, both over the 60-d period and during the day (CV 2.5-7 per cent). The CV within subjects for vitamin B1, B2 and B6 concentrations in blood ranged from 6 to 12 per cent, the variations of the corresponding erythrocyte enzyme activities were smaller. It is remarkable that the CV within subjects of most variables studied was not higher during the period on the habitual diet. We conclude that casual blood sampling is insufficient for an evaluation of the vitamin B status of an individual. The high intra-individual variability of 24-h vitamin B1 and B2 urinary excretions indicates that in the assessment of the vitamin status or intake of an individual the importance of these excretion figures is limited. The 'a-values' of the B vitamins may predict vitamin status better than the concentrations of the vitamins in blood or the activities of the corresponding enzymes. The variability of the parameters of vitamin B status over the day (CV 3-11 per cent) suggests that the values of these parameters depend on the time of the day at which samples are taken. PMID- 2261899 TI - Breast milk folic acid and zinc concentrations of lactating, low socioeconomic, Amazonian women and the effect of age and parity on the same two nutrients. AB - The levels of folic acid and zinc in breast milk of about 25 women in their first trimester of lactation from each of eight towns in the Brazilian Amazon basin were determined. In order to compare the effects of age and parity on the breast milk folate and zinc levels, the results were analysed together. Thirty-one (60 per cent) of the women in their first month of lactation and 35 (51.5 per cent) in their second month had milk total folate levels below the calculated lower limit of adequacy; only 21 (47 per cent) of the women in their third month of lactation had milk total folate concentrations below the same limit. The breast milk zinc levels, however, were worse, with 35 (95 per cent) and 61 (97 per cent) of the women in their first and second months of lactation and all the women in their third month of lactation having values below the calculated lower limit of adequacy. Both in the case of total folate and zinc, the calculated lower limits of adequacy were obtained from the respective Recommended Dietary Allowances (RDAs) of a 0-6 month old infant and the average milk production of lactating women. While the mean breast milk folate levels (both total and free) showed no significant changes during the months of lactation, the average milk zinc levels showed a significant decrease between the first and second and first and third months of lactation. The age of the women did not significantly influence either the breast milk folate or zinc levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261900 TI - Dietary intervention in breast cancer patients: effects on dietary habits and nutrient intake. AB - Effects of dietary intervention on dietary habits and nutrient levels were studied in 240 women aged 50-65 years who had been operated for a stage I-II breast cancer. Following surgery the women who had participated in a dietary history interview were randomly assigned to one of two groups. The intervention group (n = 121) received individual dietary counselling aimed at reducing dietary fat intake to 20-25 per cent of energy (E per cent) while increasing intake of carbohydrates. No dietary advice was given to women assigned to the control group (n = 119). There was no significant difference between the groups in terms of base-line nutrient intake except for a higher energy intake in the control group (P less than 0.05). Sixty-three (52 per cent) of the women in the intervention group and 106 (89 per cent) of the women in the control group completed the 2 year follow-up. Energy intake decreased after 2 years in both groups and the difference between the groups remained (P less than 0.01). Total fat intake decreased in the intervention group by 12.9-23.3 E per cent after 2 years and by 3.1 E per cent in the control group. The intake of carbohydrates increased from 46.2 to 57.2 E per cent in the intervention group and from 46.2 to 48.9 E per cent in the control group. The study shows that dietary habits and intake of nutrients can be altered through dietary counselling to breast cancer patients, and that such changes are long lasting. PMID- 2261902 TI - Thyroid carcinoma. PMID- 2261901 TI - Human adipose tissue glycogen levels and responses to carbohydrate feeding. AB - Glycogen has long been known to be present in adipose tissue, but its role is not clear. It has not been measured in human adipose tissue. We have investigated methods for its measurement using rat adipose tissue, and measured levels in humans. Glycogen in rat adipose tissue was found to be labile, necessitating rapid sample preservation. Levels in random biopsies of human adipose tissue were variable, but consistent with values for other species (0.06-0.78 mg/g wet weight; n = 5). After overnight fast, consistent low levels were found (0.04-0.08 mg/g wet weight; n = 6); these increased after eating a high-carbohydrate diet (800 g/d for 2.5 d), to 0.10-1.95 mg/g wet weight (P less than 0.05). Human adipose tissue glycogen appears to play a minor role in whole-body glucose homeostasis, but may have an important local role in the regulation of lipogenesis. PMID- 2261903 TI - Progress in thyroid cancer. AB - The last decade has seen significant advances in our understanding of thyroid cancers, in the areas of the molecular genetics and biology of these tumors, in effective use of preoperative diagnostic tools, and in appropriate long-term follow-up care. Studies of the roles of oncogenes, growth factors, and familial susceptibility factors offer the potential for further improvement in making early, accurate diagnoses. Objective prognostic scoring systems, now under development, can accurately separate the minority of papillary and follicular thyroid cancer patients at high risk for recurrence and mortality from the majority who do not need aggressive treatment. These systems will permit effective design of future studies of the impact on disease outcome of radioactive iodine treatment and follow-up testing by new imaging methods on disease outcome. PMID- 2261904 TI - Radiation-induced thyroid tumors. AB - Radiation treatments administered decades ago to children for benign conditions of the head and neck area have resulted in thyroid, salivary, neural, and parathyroid tumors. Even now, many years later, these tumors are continuing to occur. Because thyroid cancer in older people tends to be more aggressive, it is increasingly important to continue careful observation of irradiated individuals. PMID- 2261905 TI - Contribution of intraoperative pathology evaluation to surgical management of thyroid nodules. AB - With adequate experience, needle biopsy findings become as reliable or more so than frozen section diagnoses for surgical planning. Each institution must determine for itself the relative reliability of these two procedures before establishing management policies. Reduction or elimination of useless or redundant frozen section procedures reduces costs as well as anesthesia duration. PMID- 2261906 TI - Papillary thyroid carcinoma. AB - Multiple prognostic factors for outcome in papillary thyroid carcinoma are identified. For a cohort of 1500 consecutive patients followed an average of 16 years, survival rates for tumor recurrence and cause-specific mortality are described. Risk groups derived from novel prognostic scoring or staging systems and the role of DNA ploidy testing are discussed specifically. Lastly, controversies are reviewed regarding the extent of primary surgical resection and the efficacy of postoperative radioiodine remnant ablation in papillary thyroid cancer. PMID- 2261907 TI - Follicular and Hurthle cell carcinoma of the thyroid. AB - Follicular and Hurthle cell thyroid cancers account for about one fifth of thyroid cancers in the United States. Diagnosis can be difficult, despite the use of fine needle biopsy, and surgery is often necessary to make a definitive diagnosis. Total thyroidectomy is the treatment of choice, and in the case of follicular cancer, radioiodine ablation is usually performed. Distant metastatic disease can also be treated with radioiodine. For Hurthle cell tumors, radioiodine therapy is unlikely to be beneficial. PMID- 2261908 TI - Thyrotoxicosis caused by thyroid cancer. AB - Well-differentiated follicular carcinoma causing thyrotoxicosis is a rare entity. The age and sex distribution is no different from that of other patients with follicular carcinoma, with 87% older than the age of 40 and a female:male ratio of 3:1. The clinical presentation is similar to that of Graves' patients except that evidence of metastatic disease is often present (soft tissue masses, bone pain). The metastases are in the usual locations (bone, lung, mediastinum) and are often bulky. Despite the poor efficiency of iodine uptake and thyroid hormone production, the large tumor mass is capable of producing excessive hormone. Laboratory data confirm the hyperthyroid state, but the occurrence of T3 elevations with normal T4 levels is common, and T3 toxicosis may be missed if only T4 levels are measured. The role of thyroid stimulating immunoglobulins is still evolving, but such stimulators may support the growth of metastatic thyroid carcinoma and promote the development of hyperthyroidism. The treatment of these patients varied. Most had thyroidectomy followed by 131I therapy. Dosimetry allows for the administration of the largest dose of 131I with acceptable side effects. A good response to radioiodine predicted a more favorable outcome. The survival of patients with metastatic thyroid carcinoma causing hyperthyroidism does not differ from euthyroid patients with metastatic follicular disease (10 year survival, 59%). PMID- 2261909 TI - Uncommon types of thyroid cancer. AB - Anaplastic carcinoma of the thyroid is rare, making up 5% to 14% of primary malignant thyroid neoplasms. Lymphoma of the thyroid is even rarer, accounting for only 1% to 2% of thyroid malignancies. Other even rarer tumors of the thyroid, such as liposarcoma and angiosarcoma, have also been described. Although these thyroid tumors are rare, it is very important to recognize them because they may present as medical emergencies and constitute a challenge for endocrinologists, surgeons, radiotherapists, and oncologists. Anaplastic carcinoma grows rapidly and has a dismal prognosis. A significant number of patients with anaplastic carcinoma have areas of well differentiated thyroid carcinoma, which supports the hypothesis that anaplastic thyroid carcinoma arises from a pre-existing well differentiated thyroid carcinoma. Younger patients do better than older patients, and those diagnosed at an earlier stage do better than those with metastases at presentation. Multimodality therapy with surgery, radiotherapy, and chemotherapy appears to be of value. Lymphoma of the thyroid may be a primary disease or may involve the gland as part of a systemic disease. It is not usually suspected before surgery or fine-needle aspiration biopsy. Radiotherapy alone, if the disease is limited to the neck, produces good results; however, in patients with mediastinal extension, chemotherapy is indicated. PMID- 2261910 TI - Thyroid cancer in childhood. AB - The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass. PMID- 2261911 TI - Surgery in the treatment of thyroid cancer. AB - Patients with thyroid cancers offer a clinical challenge to the physician and surgeon for both treatment and research. It is evident that preoperative, intraoperative, and postoperative management can all favorably affect the clinical outcome. This demands close cooperation among internist, endocrinologist, radiotherapist, and surgeon. As surgeons, we advocate total thyroidectomy for most thyroid cancers, when it can be done safely, because recurrences will be minimized and the subsequent use of radioactive iodine treatment is facilitated. In the hands of an experienced thyroid surgeon, total thyroidectomy can be accomplished with a minimum of risk. In the future we hope to be able to identify patients at highest risk for aggressive tumor behavior and select these patients for the most aggressive treatment plans. In other cases early detection by surveillance of patients at risk for thyroid cancer, particularly medullary thyroid cancer, has already favorably affected prognosis by allowing treatment at an earlier stage of disease. PMID- 2261912 TI - Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. AB - 131I continues to be one of the safest and most effective methods of diagnosing and treating metastatic well differentiated thyroid cancer. It is not without risk, however, and must be judiciously applied to carefully prepared and selected patients. PMID- 2261913 TI - Long-term management of differentiated thyroid cancer. AB - The surveillance and long-term management of patients with differentiated thyroid cancer are highly dependent upon the individual patient's risk for recurrent disease. A 30-year-old woman who presents with a 1-cm intrathyroidal papillary cancer requires minimal surveillance following primary therapy: yearly examinations and thyroglobulin measurements on L-thyroxine suppressive therapy, periodic chest radiographs, and initially, periodic neck ultrasound examinations if the right equipment is available. These should be sufficient to identify the unexpected neck or distant recurrence. A 65-year-old man who presents with a 4-cm follicular cancer invading the thyroid capsule and intrathyroidal blood vessels needs more extensive surveillance. In addition to chest radiographs, neck ultrasound studies, and serum thyroglobulin measurements while the patient is off L-thyroxine therapy, total-body 131I scanning should be done 12 months after remnant ablation, and even if no uptake is demonstrated, 131I scanning should be repeated at 24 or 60 months. Any patient who presents with grossly invasive or metastatic disease should be treated aggressively. If feasible, aggressive surgical treatment of recurrent disease is optimal and may be curative. 131I scanning and treatment may be repeated at 6- to 12-month intervals for slow growing functional metastases. Rapidly growing metastases should be treated by external beam radiotherapy, which can follow surgical debulking, or be combined with radioiodine or chemotherapy. Unfortunately, chemotherapy is of limited value in late metastatic disease, however, rarely it results in prolonged remission. PMID- 2261914 TI - Ablative radioactive iodine therapy for apparently localized thyroid carcinoma. A decision analytic perspective. AB - Adjuvant therapy with ablative radioiodine after surgical resection of apparently localized thyroid carcinoma remains controversial because of the favorable prognosis of thyroid carcinoma and the risk of leukemia from the radioiodine. No controlled trials have been performed to examine this issue. We constructed a decision analytic model to examine whether patients with apparently localized thyroid carcinoma should receive radioiodine. Our analysis suggests that radioiodine modestly improves life expectancy by 2 to 15 months, depending on the patient's age and sex. This model predicts that the benefit of a reduction in the likelihood of recurrence outweighs the risk of leukemia from radioiodine. PMID- 2261915 TI - Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock. AB - The role of anti-endotoxin antibodies in the management of gram-negative bacteremia and the experimental and clinical studies on the cross-protection afforded by core LPS antibodies are reviewed. These studies did not achieve clarification of the epitope(s) and effector mechanism(s) involved in protection. Recently, two anti-lipid A IgM monoclonal antibodies, designated E5 and HA-1A, have been investigated in patients with gram-negative bacterial infections and clinical manifestations of septicemia. E5 reduced the mortality of patients if they were not in shock, whether they were bacteremic or not. A confirmatory study has been initiated. In contrast to E5, HA-1A protected patients whether they were in shock or not, but only when they were bacteremic at randomization. Although these studies suggest beneficial effects, the type of patients who may benefit from this expensive therapy should be further defined. Further investigations are needed to clarify the mechanisms of protection of these antibodies. PMID- 2261916 TI - Detection of borderline oxacillin-resistant Staphylococcus aureus and differentiation from methicillin-resistant strains. AB - Eighty-eight Staphylococcus aureus clinical isolates meeting criteria for borderline oxacillin resistance (intermediate susceptibility or resistance to oxacillin but susceptibility to amoxicillin/clavulanic acid upon disk diffusion testing) were studied to determine optimal test techniques and conditions for differentiating borderline oxacillin-resistant Staphylococcus aureus (BORSA) from methicillin-resistant Staphylococcus aureus (MRSA). Further testing revealed three distinct resistance patterns: 61 strains (69%) consistently met BORSA criteria and had average beta-lactamase levels five- to six-fold higher than oxacillin-susceptible controls; 11 strains (13%) were markedly heteroresistant MRSA with delayed appearance of resistant colonies leading to spurious susceptibility to amoxicillin/clavulanic acid; 16 strains (18%) appeared to be oxacillin-susceptible on repetitive testing. Under conditions used to elicit intrinsic methicillin resistance in Staphylococcus aureus, a large percentage of BORSA appeared resistant to amoxicillin/clavulanic acid. This clearly shows that BORSA may be misidentified as MRSA while heteroresistant MRSA may appear to be BORSA. It is concluded that amoxicillin/clavulanic acid zone sizes should be measured after a full 24 hours of incubation, that susceptibility testing of Staphylococcus aureus under certain environmental conditions should be interpreted with caution, and that MIC testing is the most reliable technique for differentiating these two resistance patterns in Staphylococcus aureus. PMID- 2261917 TI - Respiratory tract colonization and incidence of secondary infection during hospital treatment of community-acquired pneumonia. AB - In a prospective study of 245 patients with community-acquired pneumonia, the respiratory tract of 93 patients (38%) became colonized during hospitalization. Gram-negative rods and Candida spp. predominated, and in more than 75% of cases colonization occurred within 72 h after admission. Multivariate analysis showed that colonization was significantly associated with increasing age, presence of chronic disease, and with decreasing serum albumin and a respiratory rate of greater than 30/min on admission. Colonization was a negative prognostic factor, associated with a 14-fold higher mortality (10% vs. 0.7%), doubled length of hospital stay and a slower recovery. Seventeen patients developed a secondary infection. However, only two had lower respiratory tract infection, and one (0.4%) pneumonia verified by X-ray. The previously reported high risk of respiratory superinfection in this category of patient does not seem to apply today. PMID- 2261918 TI - Antigenicity of fractions of Helicobacter pylori prepared by fast protein liquid chromatography and urease captured by monoclonal antibodies. AB - The antigenicity of Helicobacter pylori protein fractions separated by fast protein liquid chromatography size exclusion was investigated by EIA with sera from patients of well defined Helicobacter pylori status. The antigenic material of Helicobacter pylori was confined to fractions 8 and 14 to 21. Urease containing fractions (14/15) and flagella containing fractions (17/18) were identified. Fraction 8 non-specifically bound human immunoglobulin as demonstrated by the binding of Helicobacter pylori negative sera. The remaining fractions 14 to 21 when used individually as EIA antigens were 91-100% specific, however fractions 16 to 19 showed a reduced sensitivity (78%) compared with the acid extract (95%). The urease fractions were 91% sensitive. Purified urease antigen captured by antiurease monoclonal antibodies was 83% sensitive and 93.3% specific. PMID- 2261919 TI - Persistent colonization of carbon dioxide incubators with Candida parapsilosis. AB - Recurrent contamination of bacteriological specimens with Candida parapsilosis led to epidemiological investigations which indicated persistent colonization of carbon dioxide incubators as the most likely source. Changes in the technical arrangements and institution of a meticulous cleansing protocol eliminated contamination of specimens but not colonization of the incubators. Tests for tolerance of 17% NaCl and survival at 50 degrees C, and SDS-PAGE analysis of crude cell extracts allowed discrimination between epidemic and non-epidemic isolates, while enzyme profile analysis and susceptibility studies failed as typing methods. PMID- 2261920 TI - Improved medium for storage and transportation of thermophilic campylobacters. AB - A medium for storage and transportation of thermophilic campylobacter cultures was developed. The medium contains brucella broth with 0.16% or 0.3% agar, 5% human blood, a growth supplement which enhances aerotolerance and an antibiotic supplement. Using this medium all cultures tested were recovered after 48 days at 4 degrees C, 56 days at 37 degrees C and 32 days at room temperature. Some of the cultures even remained viable for up to three months at 4 degrees C and 56 days at room temperature. The blackening of the medium by H2S positive cultures offers an indication as to the biotype. PMID- 2261921 TI - Production of cytotoxic necrotizing factor, verocytotoxin and haemolysin by pyelonephritogenic Escherichia coli. AB - Two hundred and thirty-two strains of Escherichia coli isolated from children with non-obstructive acute pyelonephritis (n = 65), women with non-obstructive acute pyelonephritis (n = 63) and the faecal flora of healthy children (n = 33) and adults (n = 71) were examined for cytotoxic necrotizing factor production, haemolysin synthesis, verocytotoxin production and expression of mannose resistant haemaglutination of human erythrocytes. Forty-eight per cent of the pyelonephritogenic Escherichia coli strains produced cytotoxic necrotizing factor and 61% produced haemolysin compared to 25% and 27% of faecal control strains (p less than 0.001 and p less than 0.001 respectively). Cytotoxic necrotizing factor production did not occur among the non-haemolytic Escherichia coli strains which confirms the close association between these two toxic factors. The bacterial phenotypes producing both haemolysin and cytotoxic necrotizing factor, and the phenotype expressing both these toxic factors and mannose-resistant haemagglutination occurred significantly more often in pyelonephritogenic strains than in faecal isolates (p less than 0.001). Haemolytic strains without the ability to produce cytotoxic necrotizing factor were more common in faecal isolates than in uropathogenic strains (p = 0.05). Strains lacking the ability to synthesize both these toxins were also over-represented in faecal isolates (p less than 0.01). PMID- 2261922 TI - Comparison of an indirect fluorescent antibody test and stool examination for the diagnosis of cryptosporidiosis. AB - A total of 342 patients, 70 with AIDS and 272 without AIDS, who had gastro intestinal illness were selected for tests for cryptosporidiosis. Stool and serum specimens were obtained from each patient. The stool specimens were examined for cryptosporidial oocysts by acid-fast stain and the serum specimens were tested for specific antibodies against oocysts by an indirect fluorescent antibody (IFA) test. The oocysts were detected in stool specimens of 68 patients (19.8%), whereas specific antibodies were demonstrated in 102 patients (29.8%). The incidence of cryptosporidiosis was 47.1% in AIDS and 12.9% in non-AIDS patients as shown by stool examination, compared to 50% and 24.6% as shown by the IFA test. Based upon the finding of oocysts in stool specimens, the sensitivity and specificity of the IFA test in the diagnosis of cryptosporidiosis was 92.6% and 85.8%, respectively. PMID- 2261923 TI - Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria. AB - The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted. PMID- 2261924 TI - Effect of clavulanic acid and beta-lactamase on phagocytosis of Staphylococcus aureus. PMID- 2261925 TI - Flavimonas oryzihabitans (formerly CDC group Ve-2) bacteremia in a pediatric patient on assisted ventilation. PMID- 2261926 TI - Ileal low-pressure bladder replacement: Camey type II. Stapling technique and preliminary results (57 cases, 1987-1989). AB - In keeping with the basic principles of Camey's procedure and with a view to improve continence, we decided in 1987 to experiment with the technique of ileal low-pressure bladder replacement (Camey II). We introduced the stapling technique in order to save time and to obtain watertight, reliable sutures. 57 patients underwent a Camey II intervention following radical cystectomy. Follow-up was 3 24 months. No operation mortality was observed and only 5 perioperative complications were recorded. Continence during the day and at night increased rapidly with Camey II (50% at 3 months, 90% at 6 months). Camey II improves the patients' quality of life; the procedure is simple, fast and reliable thanks to the stapling technique. PMID- 2261927 TI - Endoscopic urethrotomy versus urethrotomy plus Nd-YAG laser in the treatment of urethral stricture. AB - Between February 1987 and May 1988, 30 patients who presented with single, iatrogenic, annular strictures of the bulbar urethra were included in this prospective study. They were randomly divided into two groups; group 1: 15 patients who underwent direct-vision endoscopic urethrotomy (cold-knife incision at 12 o'clock) and group 2: 15 patients who underwent internal urethrotomy plus Nd-YAG laser. The results obtained were analyzed and compared at 1 and 2 years by clinical evaluation, uroflowmetry and retrograde-voiding urethrography. Group 1 obtained 80% good results at 1 year, falling to 60% at 2 years follow-up. Group 2 presented good results in 73.3% both at 1 and 2 years of follow-up. PMID- 2261928 TI - Analysis of sonographic pattern in prostatic cancer: comparison of longitudinal and transversal transrectal ultrasound with subsequent radical prostatectomy specimens. AB - In this study the diagnostic accuracy of transrectal ultrasonography (TRUS) in identifying prostatic cancer has been investigated. Attention was paid to the localization of tumor, capsular penetration and involvement of seminal vesicles. TRUS was performed with a 5-mHz linear array longitudinal probe as well as with a 5-mHz rotating transverse scanner. 23 patients underwent radical prostatectomy. The histological results were compared with the sonographic patterns. Transverse TRUS and longitudinal TRUS were comparable with regard to all the investigated parameters. The sensitivity and specificity for the presence or absence of tumor were 70-75 and 54%, respectively. When suspicion of capsular involvement was estimated in a prostatic lobe, a sensitivity of 89% and a specificity of 21% was found. When every separate ultrasonographically suspicious area of capsular breach was considered, there was a positive correlation of 63%. Seminal vesicle infiltration is hard to identify and TRUS has a sensitivity of only 65-74% with a specificity of 40-57%. PMID- 2261929 TI - Percutaneous transcatheter renal angioplasty: an endourological experience. AB - A series of 56 percutaneous transcatheter renal angioplasties, carried out in an endourological unit, is reviewed and compared with radiological series. The results were inferior for fibrosclerotic lesions (77 vs. 90%) and nonostial atherosclerosis (67.8 vs. 75%), but slightly superior for ostial lesions (33 vs. 20-30%) in the endourological series as compared with the radiological series. Conversely, morbidity was significantly inferior (8.9 vs. 18.6%). The endourological series compares well with the radiological series in the literature. Percutaneous transcatheter renal angioplasty should be considered a procedure belonging both to interventional radiology and to endourology. Owing to the technical difficulties and the complication rate, it should not be performed in outpatients and a surgical support team should be available in the event of a threatening renal complication. PMID- 2261930 TI - Differential diagnosis of testicular mass by cytological examination of seminal fluid collected by ejaculation or prostatic massage. AB - The cytological examination of the seminal fluid of 3 patients with painless testicular masses was performed using an ordinary conventional technique. Neoplastic cells appeared in the ejaculate or fluid from prostatic massage of all patients. The final pathologies were seminoma, choriocarcinoma and mixed teratocarcinoma. Malignant cells were no longer found in the seminal fluid after orchiectomy. This sample, noninvasive technique plus further flow cytometric study of cellular DNA contents is a great help in the preoperative differential diagnosis of testicular masses. PMID- 2261931 TI - Organ-preserving surgery in patients with urothelial tumors of the upper urinary tract. AB - The Austrian Urological Oncology Group reports on 55 organ-preserving operations in 52 patients with tumors of the upper urinary tract epithelium. The data were gathered from 12 urological departments in the country. There was no evidence of distant metastases in any of the patients at the time of surgery. The observation period ranged from 0.5 to 12 years. 69.2% (36 of 52) of the patients were alive and recurrence-free at the time of data collection, after a mean observation period of 41.4 months. 9.6% died for reasons other than cancer after an average of 18.8 months, and 21.2% were still alive with or had died due to recurrent tumors. The recurrence rate after open surgery was similar in tumors of the upper ureter or pelvis (15.3%) as in tumors of the lower ureter (17.6%). After endoscopic treatment 4 of 9 patients showed recurrences. 92% (22 of 24) of the patients with no compelling indication for organ-preserving therapy were alive and recurrence-free or had died due to other causes. Therefore organ-preserving surgery appears to be appropriate in tumors of the upper urinary tract epithelium. PMID- 2261932 TI - Intravesical interferon alfa-2b administration in the treatment of superficial bladder tumors. AB - This study was undertaken to assess the value of intravesical interferon alfa-2b treatment in preventing the recurrences of superficial transitional cell carcinoma of the bladder. A total of 30 patients aged from 33 to 78 entered the protocol. The intravesical instillations were performed once a week for 8 weeks. A solution of 10 x 10(6) IU interferon alfa-2b in 30 ml of normal saline was used. Follow-up ranged from 12 to 28 months. Of the 30 patients, 19 (63.33%) were tumor free at the end of follow-up. Of the remaining 11 patients, 7 presented with recurrent superficial tumors and 4 with invasive bladder tumors. No side effects were noted. PMID- 2261933 TI - Intravesical formalin for the treatment of massive hemorrhagic cystitis: retrospective review of 25 cases. AB - Between 1980 and 1988 25 patients with massive bladder hemorrhage were treated with intravesical instillation of 4% formalin in 19 cases and 10% in the remaining 6 cases; the contact time was 15 min in 20 cases. The etiology of the hemorrhage was cyclophosphamide therapy (1 case), pelvic radiotherapy (15 cases) and infiltrating bladder cancer in the remaining 9 cases. In 10 cases, the instillation of formalin was performed in bladders with a prior supravesical diversion. Complications included 1 case of vesicorectal fistula, 1 case of uretero-hydronephrosis and 1 case of vesical extravasation of formalin when a concentration of 10% was used at a volume superior to 50 ml. The only complication seen with 4% formalin was 1 case of upper urinary tract dilatation. Good results were obtained in 88% of cases, who achieved correct hemostasis during a mean of 4 months. PMID- 2261934 TI - Diagnosis and treatment of retrocaval ureter. AB - 34 cases of retrocaval ureter of our country, including 2 of our hospital, were studied. The embryologic pathology, diagnosis and treatment of the disorder are discussed. The choice of operative methods and 'vena cava supporter' are also described. PMID- 2261935 TI - Management of painful caliceal stones by extracorporeal shock wave lithotripsy. AB - One hundred and seven patients with caliceal stones causing flank pain were treated by extracorporeal shock wave lithotripsy (ESWL), followed up and reviewed. The total stone-free rate 3 months after ESWL was 38.8%. The total pain free rate was 50.5%. The pain-free rate was 85% in the stone-free group and 29% in the group with residual stones. No significant differences between the stone free rate and the duration of pain or age was noted. Patients with abnormal intravenous pyelography (IVP) had a lower stone-free rate than patients with normal IVP (16 vs. 45%, p less than 0.05). The complications included: 6 cases of stone street formation with spontaneous passage; 1 case of stone street formation needing percutaneous nephrolithotomy for drainage; 1 perirenal hematoma; 9 cases of severe colic pain following ESWL; 3 cases of fever following ESWL, and 4 cases of hydronephrosis due to a stone in the ureterovesicle junction. These results show that ESWL is an effective, noninvasive treatment for painful caliceal stones. PMID- 2261936 TI - Value of in-line and out-of-line ultrasound targeting in extracorporeal shock wave lithotripsy. AB - Acoustic inhomogeneities of body tissue may deflect diagnostic ultrasound waves as well as therapeutic shock waves. The influence of incorrect ultrasound targeting and shock wave application due to these deflection effects has been examined quantitatively by means of a two-dimensional physical model. The accuracy of in-line and out-of-line targeting has been determined. Calculations on 2 stone patients show that in-line deflection effects remain below 2 mm, while they reach values up to 6 mm for out-of-line systems. These results, confirmed by first clinical observations done by others, indicate that in-line ultrasound targeting is superior to out-of-line targeting. PMID- 2261937 TI - Effect of indomethacin on unilateral obstructed renal pelvis and on ureteral peristalsis. Experimental study in awake sheep. AB - An experimental model to study the physiology of the obstructed kidney in awake sheep is described. Unilaterally, a kidney was obstructed, and the pressure in the renal pelvis was measured before and after intravenous injection of indomethacin. This experiment study on awake sheep enabled us to compare the clinical behavior of the animal with the recorded objective data, to demonstrate the rapid decrease in pressure in the obstructed renal pelvis. In addition, we observed a decrease in ureteral peristalsis frequency following the injection of indomethacin. PMID- 2261939 TI - Hypertension and ischemic heart disease. PMID- 2261938 TI - A new technical alternative in the surgery for retroperitoneal fibrosis: the Gore Tex surgical membrane. AB - The case of a male patient with retroperitoneal fibrosis secondary to an abdominal aortic aneurysm which was surgically treated with success, is presented herein. What is considered technically new is the management of the ureters after surgical lysis. An expanded polytetrafluoroethylene Gore-Tex surgical membrane, initially developed for pericardial closure after open-heart surgery, was used to isolate the bifurcated aortofemoral graft from the duodenum and the ureters from the vascular prosthesis and surrounding retroperitoneal tissues. This is considered to be a simple and safe technique and a technical alternative when dealing with this complex situation. To date, there has been no other description of such a technique using this material. The potential value of this material to prevent reencasement in retroperitoneal fibrosis from other origins should be kept in mind. PMID- 2261940 TI - Does psychological stress contribute to the development of hypertension and coronary heart disease? AB - The role of mental stress in the development of hypertension and coronary heart disease remains uncertain. Its effects are likely to depend on an interaction of at least three factors: the nature of the stressor, its perception by the individual, and the individual's physiological susceptibility. This type of interaction is supported by animal studies. Most experimental studies in man have measured the cardiovascular response to acute laboratory stressors, on the assumption that subjects showing greater reactivity are at higher risk of developing cardiovascular disease. Experimental support for this "reactivity hypothesis" is limited, and the technique suffers from a number of limitations, such as an emphasis on acute rather than chronic effects, and a doubtful relevance to real-life stressors. It is possible, however, that transient surges of autonomic activity occurring in response to behavioral stimuli could trigger acute cardiac events. The role of environmental stressors can be studied by ambulatory monitoring techniques. Using the Karasek Job Content Survey (a known predictor of coronary heart disease), we have found that men in high strain jobs (defined by a combination of high demands and low control) are more likely to be hypertensive, and to show left ventricular hypertrophy than men in less stressful jobs. PMID- 2261941 TI - Retardation of development and progression of coronary atherosclerosis: a new indication for calcium antagonists? AB - Development of atherosclerotic lesions in animals, preferrably induced by a high cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2 3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1 year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261942 TI - Verapamil in antihypertensive treatment of patients on renal replacement therapy- clinical implications and pharmacokinetics. AB - Twenty-eight hypertensive patients on renal replacement therapy (HD, HF, PD) were treated with verapamil (Isoptin RR-slow release) in an open label study. Blood pressure was satisfactorily reduced in 21 patients (84%). Due to adverse reactions the treatment had to be discontinued in 4 patients. Verapamil clearances were calculated according to different dialysis methods. No changes in dose or mode of application of verapamil were necessary using any mode of renal replacement therapy. PMID- 2261943 TI - Antihypertensive and renal effects of enalapril and slow-release verapamil in essential hypertension. A double-blind, randomized study. AB - The renal, metabolic and antihypertensive effects of enalapril (E) and slow release verapamil (V) were compared in a 2-month double-blind crossover trial in 22 patients with newly discovered essential hypertension. The glomerular filtration rate and renal vascular resistance were unaltered: renal blood flow was slightly decreased by V. Serum Ca2+ increased and Na+ excretion declined after V. Serum lipids, glucose, and erythrocyte electrolytes were unchanged. Blood pressure (BP) was lower with E after half the maximum dosage compared with V, but similar BP reductions were obtained after 2 months with the maximum dosage. PMID- 2261944 TI - Immunocytochemistry of intermediate filaments in cultured arterial smooth muscle cells: differences in desmin and vimentin expression related to cell of origin and/or plating time. AB - The objective of this study was to determine whether intermediate filament expression, including desmin and vimentin, in cultured smooth muscle cells (SMCs) is related to cyto-differentiation or proliferation. Using antibodies to desmin and vimentin, we studied by immunoperoxidase technique the distribution of these proteins in subcultured SMCs derived from porcine aorta and coronary artery. In addition, the proliferative potentiality of the cells was estimated by the incorporation of [3H]thymidine into DNA. The frequency of desmin-positive cells in coronary arterial SMCs of 3 and 6 population doubling levels was significantly higher as compared to findings with the aortic SMCs and depended on the plating time. No difference was evident at the 12 population doubling level. In contrast, vimentin was present in the majority of both aortic and coronary arterial SMCs. With regard to the localization of vimentin, two cell types were observed, one had reaction products to vimentin in both perinuclear and cell-peripheral areas (type-I cell), the other only in the cell-peripheral region (type-II cell). The relative proportion of the type-I and -II cells varied with the period of culture. Most of the SMCs showed the type-I cell on the first day and the number of type-II cells was increased on the sixth day. Quiescent SMCs in serum-free media had the same percentage of desmin-positive cells and frequency distribution of type-I and -II cells as did the proliferating SMCs incubated in media containing 5% serum. These results suggest that intermediate filament expression, including desmin and vimentin in cultured SMCs, is related to cell origin and/or plating time, but not to the proliferating activity, per se. PMID- 2261945 TI - Bovine coronavirus antigen in the host cell plasmalemma. AB - Expression of bovine coronavirus (BCV) antigen in the plasmalemma of epithelioid human rectal tumor (HRT-18) and fibroblastic bovine fetal spleen (BFS) cell lines was traced by immunofluorescence and immunoelectron microscopy facilitated by colloidal gold. Cytoplasmic fluorescence was first observed at 12 hr postinfection (h.p.i) in infected HRT-18 cultures. This fluorescence coincided with the appearance of cell surface antigen reacting with colloidal gold-labeled antibodies to BCV antigens. At 24 h.p.i the amount of viral antigens at the surface of HRT-18 had increased, although cytoplasmic fluorescence remained constant. Infected BFS cells but not HRT-18 cells formed polykaryons when incubated in the presence of trypsin. One viral antigen in the plasma membrane of BFS cells was thus identified as the S glycoprotein with a fusion domain. In contrast to HRT-18 cells, the overall amount of BCV antigens at the surface of BFS cells remained constant after the onset of fusion. Analysis of the labeling characteristics established that the gold-marked-sites represented de novo expression of BCV antigen in the plasma membrane of infected cells. PMID- 2261946 TI - Lipid metabolism in the inflammatory lesion of a mouse model of delayed type hypersensitivity. I. Increased acylCoA:cholesterol acyltransferase activity as an integral component of the inflammatory response. AB - Lipid metabolism was studied in a normal model of delayed type hypersensitivity to methylated bovine serum albumin (MBSA). Following initial sensitization to a single injection of MBSA, MBSA-soaked millipore filter disks (10 mm diam) were implanted in subcutaneous pockets and the course of development and the resolution of the inflammatory lesions were followed biochemically for 35 days. Of particular interest were our observations that the activity of the cholesterol esterifying enzyme, which is attributed to acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) was increased up to 38-fold in the developing inflammatory lesion and represented the single most dramatic alteration in lipid metabolism to occur. As the lesions began to show histological evidence of resolving (between 21 and 35 days), ACAT activity declined toward basal levels. The data suggest the possibility that the ACAT reaction is an important component of the inflammatory response and, as such, offers the possibility of a novel approach to controlling the inflammatory process through ACAT inhibition. PMID- 2261947 TI - Cadmium toxicity in perinatal rat hepatocytes: electron microscopy, X-ray microanalysis, and morphometric analysis. AB - Effects of cadmium on the fetal and postnatal rat hepatocytes were studied with an electron microscope and an X-ray microanalyzer. Pregnant and lactating Wistar rat dams at 15 and 21 days of pregnancy and at 3 days after delivery received intraperitoneal injections of cadmium sulfate (1 mg/kg body weight) for 3 days. On the day following the last injection, the livers were isolated from the fetal and suckling rats and provided for electron microscopy. The livers from the untreated fetal and newborn rats served as control. Large bile canaliculi, which were formed by five or more hepatocytes, were frequently observed in the cadmium treated perinatal rat livers. The intercellular space between each adjacent hepatocyte was widened. By X-ray microanalysis, cadmium peaks were preferentially detected out from intramitochondrial granules of the cadmium-treated hepatocytes. By morphometric analysis, the increase both in the mitochondria volume and in the number of intramitochondrial granules was evident in the cadmium-treated hepatocytes when compared to those of control. These data suggest the preferential accumulation of cadmium in mitochondria of the hepatocytes interferes with the morphogenesis of the perinatal rat liver. PMID- 2261948 TI - Clinical significance of serum pro-collagen III in chronic myeloproliferative disorders. AB - Pro-collagen III (PC III) has been proposed as a useful value for diagnosis and follow-up of myeloproliferative disorders. A significant difference is observed between polycythaemia vera (PV) and essential thrombocythaemias (ET) on one hand, and the pure erythrocytoses (PE) on the other hand, but a large overlap makes this test of low diagnostic value. High values are observed in primary and post PV myelofibrosis, but excessive PC III levels in active PV are not predictive of evolution toward myelofibrosis. PC III level is lower in myelo-suppressed patients (32P, or hydroxy-urea) than in active cases or in patients treated by phlebotomies. We conclude that PC III measurement is of low diagnostic value for discriminating PV and PE, does not appear to allow short-term prediction of evolution to myelofibrosis, but may be useful to evaluate the role of treatment in delaying progression of PV toward myelofibrosis. PMID- 2261949 TI - In vivo elaboration of CSF in acute inflammation: proportionality to the intensity of the inflammatory stimulus and requirement of T lymphocytes. AB - The colony-stimulating factor(s) (CSF) that stimulates the in vitro growth of bone marrow granulocyte-monocyte progenitors (CFU-GM) increases in the serum of mice challenged by an aseptic abscess induced by copper rod insertion. The effect of the inflammation on the increase of serum CSF is dose-related. The creation of 3 aseptic abscesses indeed results in a higher and longer elevation of serum CSF than 1 abscess. Serum CSF also increases in parallel with the rise in bone marrow CFU-GM; this is consistent with the CSF playing a role in regulation of haematopoiesis in vivo. From previous studies, it appears that T lymphocytes play a central role in the regulation of haematopoiesis. In order to determine the role of T lymphocytes in the inflammation response, cyclosporin A (CyA), an inhibitor of T lymphocyte function, was given in vivo, 2 days before inflammation induction. CyA abrogates the increase in both serum CSF and CFU-GM. Furthermore, a lower increase in serum CSF was observed in copper-implanted nude mice. These results suggest that the CSF production induced by inflammation requires the functional integrity of T lymphocytes. PMID- 2261950 TI - Heat production rate in blood lymphocytes as a prognostic factor in non-Hodgkin's lymphoma. AB - The heat production rate in peripheral blood lymphocytes was evaluated by direct calorimetry in 76 untreated adults with non-Hodgkin's lymphoma (NHL). Elevated values were recorded for 20 out of 54 patients with lymphomas of high or intermediate malignancy grade (37%) and for 1 out of 22 patients (5%) with low grade lymphomas (p = 0.01). Median survival was 39 months for patients with normal values and 8.5 months for those with elevated values (p = 0.005). In a subgroup of 38 patients with high or intermediate grade NHL stage III-IV, 17 patients with abnormally high lymphocyte heat production rates had a significantly shorter survival than 21 patients with normal values (p = 0.01). In a multivariate analysis the prognostic impact of lymphocyte heat production was superior to histologic malignancy grade, clinical stage and age. PMID- 2261951 TI - Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG). AB - 63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded. PMID- 2261952 TI - Endogenous BFU-E in peripheral blood in diagnosis of polycythemia vera. AB - Erythroid progenitors (CFU-E and BFU-E) growth in vitro from bone marrow and peripheral blood of patients with polycythemia vera (PV) was studied using a methylcellulose culture technique. The aim of the study was to find out whether the in vitro colony formation of peripheral blood could be used in the differential diagnosis of PV. In all 25 patients studied, endogenous colonies were found in the bone marrow and peripheral blood. The parallel study of both bone marrow and peripheral blood erythroid progenitors indicates that the presence of endogenous BFU-E in peripheral blood is a dependable test for PV. The results presented here showed that the abnormalities in PV erythroid progenitors are expressed at the level of both CFU-E and BFU-E, suggesting multiple changes in the erythroid progenitors. Our finding indicate that peripheral blood BFU-E differ from bone marrow BFU-E with regard to their dependence for further differentiation on BPA, the activity present in PHA-LCM. PMID- 2261953 TI - Recombinant human erythroid potentiating activity enhances the effect of erythropoietin in mice. AB - Endotoxin-free purified recombinant human erythroid potentiating activity (EPA) was administered to mice either alone or concomitantly with recombinant human erythropoietin (Epo). Epo treatment alone caused an increased hematocrit and reticulocyte count in the peripheral blood. In the spleen, the number of morphologically recognizable erythroid cells, CFU-E and BFU-E was also increased. Concomitant administration of EPA with Epo further enhanced erythropoiesis as judged by the same parameters. No significant effect on granulopoiesis was observed in association with Epo or combined Epo and EPA treatment. Our data indicates that EPA is active in vivo in augmenting the erythropoietic response to Epo. PMID- 2261954 TI - High serum immunoreactive erythropoietin in leukaemic patients with bone marrow insufficiency of erythropoiesis. PMID- 2261955 TI - Bleeding diathesis associated with beta-lactam antibiotics. PMID- 2261956 TI - "Protracted pulse" chemotherapy for refractory myeloma: a preliminary report. PMID- 2261957 TI - Lytic bone lesions in polycythaemia rubra vera. PMID- 2261958 TI - Cytopenias and anti-Ro (SS-A) antibodies: a report of 11 cases. PMID- 2261959 TI - Decreased haemoglobin and chronic immune activation in patients with gynaecologic malignancies. PMID- 2261960 TI - Life table analysis for estimation of duration of aplasia after high-dose chemotherapy. PMID- 2261961 TI - Expression of differentiation and activation antigens on peripheral blood mononuclear cells in chronic lymphocytic leukaemia (CLL) and in hairy-cell leukaemia (HCL) PMID- 2261962 TI - Home mechanical ventilation. PMID- 2261963 TI - Short-term smoking reduction is associated with reduction in measures of lower respiratory tract inflammation in heavy smokers. AB - The beneficial effect of short-term smoking reduction in reducing lower respiratory tract inflammation was assessed in 15 healthy heavy smokers. All underwent fibreoptic bronchoscopy and bronchoalveolar lavage and were then treated with at least 20 mg of nicotine gum daily. Self-reported cigarette consumption decreased from 50.7 +/- 2.3 to 18.8 +/- 1.5 (p less than 0.001) cigarettes daily, and expired CO decreased from 48.5 +/- 2.5 to 27.3 +/- 2.5 ppm (p less than 0.001). After two months, repeat bronchoscopy and bronchoalveolar lavage revealed that bronchial inflammation, as assessed by direct inspection, neutrophilia of bronchial lavage fluid, and the number of alveolar macrophages, the number of alveolar neutrophils and the concentration of neutrophil elastase alpha 1-antiprotease complex in alveolar lavage fluid, had improved significantly. The present study suggests that smoking reduction may be associated with an improvement in lower respiratory tract inflammation in heavy smokers and may, if persistent, be an alternative for smokers who cannot, or do not wish, to quit. PMID- 2261964 TI - Circulating immune complexes in sarcoidosis, a clinical role for the Raji assay? AB - Many immunological abnormalities, including circulating immune complexes (CICs), have been described in patients with sarcoidosis. The relationship of these abnormalities to clinical states is uncertain. In 31 proven cases of sarcoidosis we used the Raji assay in the investigation of the relationship between disease activity and the presence of CICs. Circulating immune complexes (greater than 49 micrograms.ml-1) were found in 11 of 14 patients with evidence of recent significant disease deterioration, whereas only one of 17 patients with chronic stable sarcoidosis demonstrated CICs (p less than 0.001). At follow-up, it was found that eight of the 11 cases with active disease and detectable CICs had resolved clinically. Resolution was accompanied by normalization of CICs in seven and persistence in one. The remaining three patients did not improve clinically and continued to demonstrate CICs. Measurements of complement levels did not demonstrate any significant difference between the two groups of patients. It is concluded that elevated levels of CICs, as detected by the Raji assay, are commonly found in association with significantly deteriorating sarcoidosis, often normalize following disease improvement and, consequently, may have a useful clinical role as a marker of activity. PMID- 2261965 TI - Enhanced reactivity to bradykinin, angiotensin I and the effect of captopril in the pulmonary vasculature of chronically hypoxic rats. AB - We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2261966 TI - First-time treatment with steroids in bronchial asthma: comparison of the effects of inhaled beclomethasone and of oral prednisone on airway function, bronchial reactivity and hypothalamic-pituitary-adrenal axis. AB - In a double-blind cross-over study of 12 asthmatic patients the effects of 1,000 micrograms.day-1 beclomethasone dipropionate (BDP) on airway function, bronchial reactivity and hypothalamic-pituitary-adrenal (HPA) axis have been compared to those of 15 mg.day-1 oral prednisone (PRD). None of the patients had ever received corticosteroids before. Fourteen days treatment with either of both steroids improved airway function, both subjectively and objectively. Both steroids slightly reduced the responsiveness to histamine. PRD suppressed the corticotrophin-releasing factor (CRF) stimulated cortisol release more than BDP did, whereas there was no significant change in adrenocorticotrophic hormone (ACTH) release. The results indicate that short-term treatment with 1,000 micrograms.day-1 BDP reduces bronchial hyperreactivity (BHR) in asthmatic patients, whilst having subtle effects on HPA axis. PMID- 2261967 TI - The relationship between bronchial immunopathology and hyperresponsiveness in asthma. AB - Physiological and Immunopathological parameters were investigated in 15 patients with diagnosed asthma, and 6 non-asthmatics presenting with other chest symptoms. The 15 symptom-free asthmatics expressed bronchohyperresponsiveness with a mean provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of 1 mg histamine. None of the non-asthmatics responded to 16 mg histamine. Twenty four hours later bronchoscopy was performed and endobronchial biopsies were obtained. Histological staining of frozen biopsy sections revealed a mononuclear cell infiltrate in all 15 asthmatics, while only 1 of the 6 non asthmatics showed mild inflammation. Monoclonal antibodies were used to identify subsets of lymphocytes, activation markers, macrophages, and HLA-DR expression within the peribronchial infiltrates. In all samples, activated T-cells and macrophages were identified and HLA-DR expression was found to be raised, but the CD4: CD8 ratio was highly variable. No clear relationship was found between cellular distribution and measured lung function parameters. A highly significant correlation was found between the level of HLA-DR expression on the infiltrating cells (quantified microdensitometrically) and bronchial hyperresponsiveness. These results show for the first time that a chronic T-cell-mediated immune response is present in the bronchial tissue of asymptomatic asthmatics, and that the HLA-DR expression promoted correlates with the hyperresponsive status. These data promote the hypothesis that a T-cell-mediated response contributes to a predisposition to bronchial hyperresponsiveness in asthmatics. PMID- 2261968 TI - Effects of exposure to welding fume: an experimental study in sheep. AB - Welding fume contains various metals and pulmonary effects from their inhalation are largely unknown. We have studied the effects of exposure to welding fume in sheep. The animals were exposed to either a bolus dose of welding fume solution or to five weeks daily exposure. Lung physiology parameters were studied and biopsies taken. Magnetopneumography was used to register the longterm exposure. Acutely exposed animals had elevated pulmonary arterial pressure. Arterial oxygen tension was reduced after fume instillation. These animals had accumulation of iron (Fe), magnesium (Mg) and manganese (Mn) in the lungs. Mn was elevated 40 times. Longterm exposed sheep increased the iron oxide accumulation significantly in lungs as seen with the magnetopneumographic technique. Following long term exposure, Mn was the metal most heavily retained in the lungs. Metals like Mn, Fe and Mg retained in the lungs can possibly give negative health effects. Besides this, the metals could be used for quantitation of welding fume exposure. PMID- 2261969 TI - Airway responsiveness following wheezy bronchitis in infants. AB - The study was undertaken to assess the airway function and its response to carbachol and salbutamol in infants recovering from wheezy bronchitis. In 82 children aged 3-33 mths, free from wheeze at the time of testing, and in 14 healthy infants, airway resistance (Raw) and thoracic gas volume (TGV) were measured using a body plethysmograph. Specific airway resistance (sRaw = Raw x TGV) was calculated. Increasing doses of nebulized carbachol were applied to challenge the airways. After a positive reaction had been achieved, 0.1 mg of nebulized salbutamol was administered. Raw was monitored during the whole procedure. In 23 of the 82 children the study was repeated after nine months on average. Within this period Raw remained elevated, whereas TGV and sRaw fell considerably (TGV from 37.9 to 28.2 ml.kg-1, p less than 0.01; sRaw from 0.78 to 0.63 kPa.s-1, p less than 0.01). Airway responsiveness also dropped during the observation period (mean log provocation dose producing 50% fall (PD50) 0.026 and 0.358, p less than 0.01). In comparison with controls the study infants responded to lower doses of carbachol (mean log PD50 0.610 and 0.031, respectively, p less than 0.01). Airway responsiveness was not related to baseline airway calibre or to signs of atopy. sRaw returned to baseline 2-5 min following salbutamol. The results suggest that airways of children in a symptom-free period following wheezy bronchitis have reduced patency and reveal hyperresponsiveness to carbachol. PMID- 2261970 TI - Devices for low flow O2 administration. AB - Long-term oxygen therapy requires a practical regulated oxygen delivery system which works in the home. Although face-masks are cheap and efficient, they are awkward and need removal for talking and eating. Few patients would comply with this for 15 h her day. Nasal prongs are reliable, cheap, safe and well tolerated but are wasteful of oxygen. This waste is important both practically and financially when oxygen is supplied from portable or large cylinders or from a liquid source. The Oxymizer pendants and moustache or inspiration phased delivery devices improve nasal prong efficiency. Nasopharyngeal catheters are an alternative but more invasive means of oxygen conservation. Percutaneous transtracheal catheterization is both oxygen efficient and cosmetically acceptable. As it requires an invasive surgical procedure with some serious potential complications its use should probably be reserved for those patients in whom adequate oxygenation is not achieved by standard nasal prongs. Its use is rarely justified on merely cosmetic grounds. Permanent tracheostomy is not indicated in most cases of hypoxic chronic obstructive airways disease (COAD). Nasal prongs would seem the most reasonable method of oxygen delivery. Their use with oxygen concentrators lessens the need for oxygen conservation. PMID- 2261971 TI - The role of PEEP in patients with chronic obstructive pulmonary disease during assisted ventilation. AB - In patients with acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (COPD), the intrinsic positive end expiratory pressure (PEEPi) can significantly increase workload for ventilation. It has been suggested that, in the presence of expiratory flow limitation, application of low levels of PEEP by the ventilator can be used to reduce PEEPi and therefore the magnitude of the inspiratory effort during assisted mechanical ventilation (or pressure support) and weaning. Clearly, pulmonary hyperinflation should not be further enhanced in order not to counteract the beneficial effect of removing PEEPi by decreasing respiratory muscle length and force. This use of PEEP in COPD patients is supported not only by theory, but also by recent experimental work, although sufficient clinical information is not yet available to provide a guideline for titration of the PEEP level. Therefore, application of PEEP in COPD patients requires close monitoring of the end-expiratory lung volume. This can be accomplished, among other noninvasive ways (e.g. the inductive plethysmography), by inspection of flow/volume curves during application of increasing levels of PEEP. The shape of the expiratory limb of the flow/volume curve can also suggest the presence of dynamic hyperinflation and expiratory flow limitation. PMID- 2261972 TI - Investigations of an automatic screening device (MESAM) for obstructive sleep apnoea. AB - A digital recording device developed to monitor heart rate (HR) and breathing sounds (snoring), and used to screen subjects for obstructive sleep apnoea syndrome (OSAS), was investigated. This device is called the MESAM and is currently commercially available in some western European countries. The computer based automatic scoring systems provided with the equipment and a hand-scoring technique developed at Stanford and requiring 10-15 min to perform, were used. Polysomnography and MESAM recordings were performed simultaneously on two groups of 25 sleep disorder patients (each with respiratory disturbance index greater than or less than 10). Patients were randomly monitored and records were analysed by two teams blind to the initial clinical impression, to the events which occurred during the recordings, and to each other's findings. Specificity and sensitivity were calculated for each of the MESAM scoring techniques considered, with polysomnography being selected as the recording standard, With "automatic HR scoring" specificity was 12%, sensitivity 92%; with "automatic breathing sounds (snoring)" scoring, specificity was 8% and sensitivity 96%; with "hand-scoring" specificity was 72% and sensitivity 92%. If the three scoring techniques were combined, all patients with a respiratory disturbance index (RD) greater than 10 were recognized as having OSAS. PMID- 2261973 TI - Bilateral pleural effusion due to malignant mesothelioma, diagnosed by means of immunostaining. AB - We report a patient who presented himself with a bilateral pleural effusion. Histology proved that this was caused by a malignant pleural mesothelioma. Immunostaining and DNA-flow cytometry confirmed the diagnosis. The usefulness of these rather new diagnostic techniques is discussed. PMID- 2261974 TI - Haemophilus influenzae lobar pneumonia in the father of a child with epiglottitis. AB - We present a case of Haemophilus influenzae lobar pneumonia in the father of a child admitted with acute epiglottitis caused by the same organism. The suggestion that adult, as well as child, contacts for Haemophilus influenzae epiglottitis should be prophylactically treated is discussed. PMID- 2261975 TI - Alveolar macrophages from smokers show strong intracellular fluorescence. PMID- 2261976 TI - DNA polymerase activity of tomato fruit chromoplasts. AB - DNA polymerase activity was measured in chromoplasts of ripening tomato fruits. Plastids isolated from young leaves or mature red fruits showed similar DNA polymerase activities. The same enzyme species was present in either chloroplasts or chromoplasts as judged by pH and temperature profiles, sensitivities towards different inhibitors and relative molecular mass (Mr 88 kDa). The activities analyzed showed the typical behaviour of plastid-type polymerases. The results presented here suggest that chromoplast maintain their DNA synthesis potential in fruit tissue at chloroplast levels. Consequently, the sharp decrease of the plastid chromosome transcription observed at the onset of fruit ripening could not be due to limitations in the availability of template molecules. Other mechanisms must be involved in the inhibition of chromoplast RNA synthesis. PMID- 2261977 TI - Comparison of the gamma-crystallins isolated from eye lenses of shark and carp. Unique secondary and tertiary structure of shark gamma-crystallin. AB - gamma-Crystallin isolated from the shark of cartilaginous fishes was compared with the cognate gamma-crystallin from the carp of bony fishes. Distinct differences in amino acid compositions, primary, secondary and tertiary structures were found. The most salient features of shark gamma-crystallin lie in the fact that this crystallin possessed a significant alpha-helical structure in the peptide backbone as revealed by circular dichroism study, in contrast to those orthologous gamma-crystallins from other vertebrate species including bony fishes which all show a predominant beta-sheet secondary structure. The tertiary structure as reflected in the intrinsic microenvironments of various aromatic amino acids in the native crystallins also shows unambiguous differences between these two classes of gamma-crystallins. N-Terminal sequence analysis corroborates the structural differences between shark and carp gamma-crystallins. gamma Crystallin from the more primitive shark seems to be more in line with the main evolutionary phylogeny leading to the modern mammalian gamma-crystallin. PMID- 2261978 TI - Reactions of Fe(II)-ATP and Fe(II)-citrate complexes with t-butyl hydroperoxide and cumyl hydroperoxide. AB - Rate constants for the reactions of cumyl hydroperoxide and t-butyl hydroperoxide with ferrous complexes of ATP and citrate were measured at pH 7.4. These ligands are potential chelators of iron(II) in the low-molecular weight iron pool that may catalyze oxidative degradation of biomolecules. The second-order rate constants for the reduction of cumyl hydroperoxide and t-butyl hydroperoxide by ferrous ATP are 3.1 x 10(3) and 1.3 x 10(3) M-1.s-1, respectively, at 25 degrees C and 0.11 M ionic strength. Rates of reduction by ferrous citrate are similar. Activation enthalpies for these reactions average 10 kcal/mol. PMID- 2261979 TI - Stable rightward shifts of the oxyhemoglobin dissociation curve induced by encapsulation of inositol hexaphosphate in red blood cells using electroporation. AB - Rightward shifts of 50-100% of the P50 values in the oxygen dissociation curve of intracellular hemoglobin are obtained after encapsulation of inositol hexaphosphate in mouse and dog red blood cells (RBC) by electroporation. Life spans of mouse RBC-myo-inositol hexaphosphate in circulation are unchanged from the normal RBC values. PMID- 2261980 TI - Ultraweak photoemission from dark-adapted leaves and isolated chloroplasts. AB - Dark-adapted isolated spinach chloroplasts and leaves, unlike sub-chloroplast fractions, are capable of emitting ultraweak light spontaneously (50-125 counts/s per cm2). The emission of leaves is due to two processes with activation energies of 97 and 25 kJ/mol while in isolated chloroplasts, it is the result of a single process (98 kJ/mol), as indicated by the Arrhenius plots of the intensity. Emission spectra demonstrate that the terminal step of these reactions is the excitation of chlorophyll in both samples. We suggest that the additional component in the ultraweak light emission of leaves may be related to mitochondria. PMID- 2261981 TI - Phytochrome in lower plants. Detection and partial sequence of a phytochrome gene in the moss Ceratodon purpureus using the polymerase chain reaction. AB - The polymerase chain reaction was carried out with primers hybridizing to conserved regions of the phytochrome genes. With DNA from the moss Ceratodon purpureus 5 overlapping fragments were obtained resulting in a continuous nucleotide sequence of 1474 bp. The deduced amino acid sequence showed homology of around 60% with all known phytochrome sequences. The sequences contained a conserved chromophore attachment site. In light-grown Ceratodon protonemata the phytochrome mRNA with the size of about 4.5 kb was detected. PMID- 2261982 TI - Site-directed mutagenesis of the putative catalytic residues of Trichoderma reesei cellobiohydrolase I and endoglucanase I. AB - Site directed mutagenesis has been performed to test hypotheses concerning the putative active sites of Trichoderma reesei cellobiohydrolase I and endoglucanase I. It is shown that mutagenesis of the residue E126, previously proposed to be the proton donor in CBHI, did not totally inactivate the enzyme while mutagenesis of the residue E127 in the homologous enzyme EGI resulted in complete loss of activity. These results are compared with those obtained in similar studies of other glucanases and the effects on enzymatic activity of hyperglycosylation of the yeast produced cellulases are discussed. PMID- 2261983 TI - Complete localization of the disulfide bridges and glycosylation sites in boar sperm acrosin. AB - Acrosin is a disulfide-bonded two-chain glycoprotein, which belongs to the serine proteinase family and which plays a central role in mammalian fertilization. The amino acid sequence of acrosin from different species has been recently derived by cDNA analysis. Boar sperm acrosin contains twelve cysteine residues forming two interchain and 4 intrachain disulfide bonds. Protein-chemical and mass spectroscopic analyses of fragments and subfragments obtained by proteolytic and chemical degradation of the isolated protein allowed the unambiguous localization of all disulfide bridges and glycosylation points in boar acrosin. The 12 cysteines and the glycosylated asparagines in the porcine enzyme are absolutely conserved in number and position within all known acrosin sequences. Thus, the disulfide bond and glycosylation patterns outlined here are conserved during evolution and may be important for enzyme function. PMID- 2261984 TI - CD4-affinity purification of recombinant and native HIV gp120 and comparison of the affinity constants for the receptor. AB - Soluble CD4-immunoglobulin chimeric proteins were covalently attached to CNBr activated Sepharose. This affinity matrix was used to establish a powerful new method to isolate different species of the HIV external glycoprotein gp120 from cell-free culture supernatants. Recombinant gp120 was expressed in Baculovirus infected insect cells and isolated from cell-free culture supernatants. The recombinant protein has an apparent molecular mass of 130 kDa. These two gp120 species were shown to be of identical molecular size after complete deglycosylation achieved by endoglycosidase treatment, and they bound to CD4-H gamma l with the same binding constant, that was reported for native forms of gp120 and CD4. Thus the different glycosylation of gp120 does not influence its affinity to CD4 and the gp120-CD4 complex can be reversibly dissociated. PMID- 2261985 TI - Electrophoretic separation by an improved method of fast myosin HCIIb-, HCIId-, and HCIIa-based isomyosins with specific alkali light chain combinations. AB - An improved method of electrophoresis under nondenaturing conditions separated three electrophoretically distinct isomyosin triplets when applied to rat fast twitch muscles displaying a predominance of one of the fast myosin heavy chain isoforms HCIIb, HCIId or HCIIa. The three isomyosin triplets, named FM1b-FM3b, FM1d-FM3d, FM1a-FM3a, corresponded to the three possible alkali light chain (LC) combinations (LC1f homodimer, LC1f/LC3f heterodimer, and LC3f homodimer) with each fast HC isoform. Different proportions of these various isomyosins suggested specific affinities of light chains LC1f and LC3f for the fast heavy chain isoforms. PMID- 2261986 TI - Synchronized repetitive spikes in cytoplasmic calcium in confluent monolayers of human umbilical vein endothelial cells. AB - Synchronized repetitive spikes in cytoplasmic free calcium concentration, [Ca2+]i, are evoked by histamine in confluent monolayers of human endothelial cells. The repetitive spikes, which are apparently dependent upon the establishment of cell coupling, are also induced by caffeine, indicating that they may be due to an oscillatory release of Ca2+ from the endoplasmic reticulum, and may not involve oscillations in inositol phosphates. It is suggested that synchronized repetitive spikes in [Ca2+]i might lead to oscillatory release of endothelial-derived substances such as prostacyclin, nitric oxide and endothelin, which have potent effects on the vascular system. PMID- 2261987 TI - K-252a inhibits the response of tomato cells to fungal elicitors in vivo and their microsomal protein kinase in vitro. AB - Two characteristic responses of plant cells to fungal elicitors, induction of phenylalanine ammonia-lyase activity and of ethylene biosynthesis, were studied in suspension-cultured tomato cells. Induction of both responses was completely blocked by 500 nM K-252a, a known inhibitor of mammalian protein kinases. About 100 nM K-252a caused half-maximal inhibition. In vitro, K-252a inhibited protein kinase activity in microsomal preparations from tomato cells. Inhibition was competitive with respect to ATP and had a Ki of about 15 nM. Thus, protein kinases sensitive to K-252a occur in plants and might be important for the plant's response to fungal elicitors. PMID- 2261988 TI - Simultaneous recording of Indo-1 fluorescence and Na+/Ca2+ exchange current reveals two components of Ca2(+)-release from sarcoplasmic reticulum of cardiac atrial myocytes. AB - Simultaneous measurements of intracellular Ca2(+)-concentration ([Ca2+]i) using Indo-1 and the current generated by electrogenic Na+/Ca2(+)-exchange (INaCa) have been performed on atrial myocytes from hearts of adult guinea-pigs. Whereas the fluorescence-measurements provide information on global [Ca2+]i, InaCa which is a linear function of Ca2(+)-concentration, indicates subsarcolemmal [Ca2+]. Under conditions in which intracellular Ca2(+)-transients due to Ca2(+)-release from the sarcoplasmic reticulum (SR) have been artificially slowed, a deviation between the two different Ca2(+)-signals can be found. During onset of release signals Ca2(+)-concentration seen by the membrane is higher than global [Ca2+]i. Our results provide evidence that in atrial myocytes, lacking a T-system, Ca2(+) induced Ca2(+)-release occurs first from a subsarcolemmal compartment of the SR. The resulting Ca2(+)-transient serves to trigger Ca2(+)-release from deeper SR compartments. PMID- 2261989 TI - Three phosphorylation sites in elongation factor 2. AB - Elongation factor 2 (EF-2) of rabbit reticulocytes was phosphorylated in vitro by incubation with partially purified EF-2 kinase and [gamma-32P]ATP. After exhaustive tryptic hydrolysis 4 phosphopeptides were revealed by two-dimensional peptide mapping. The phosphopeptides were isolated by high performance liquid chromatography and sequenced. A comparison of the primary structure of the phosphopeptides with that of EF-2 showed that all 4 phosphopeptides originated from one region of EF-2 located near the N-terminus that contains 3 threonine residues: Thr-53, Thr-56, Thr-58. A direct estimation of localization of radioactive phosphate in the phosphopeptides demonstrated that all the enumerated threonine residues in EF-2 can be phosphorylated in vitro. PMID- 2261990 TI - InsP3- and Ca2(+)-induced Ca2+ release in single mouse oocytes. AB - To better understand the mechanism of intracellular Ca2+ mobilization, mouse oocytes were micro-injected with 'caged'-inositol-1,4,5 triphosphate caged-InsP3) together with the Ca2+ indicator Fluo-3 to directly induce and monitor Ca2+ redistribution. Photo-released InsP3 elicits [Ca2+]i changes exhibiting several kinetic phases and threshold behaviour. Often Ca2+ oscillations were induced after a single InsP3 pulse. Autoregenerative Ca2+ transients could also be induced by injections of Ca2+ itself, demonstrating unequivocally the presence of a Ca2(+)-induced Ca2(+)-release mechanism in these cells. PMID- 2261991 TI - Mutagenesis of the gene encoding amicyanin of Paracoccus denitrificans and the resultant effect on methylamine oxidation. AB - The gene encoding the blue-copper protein amicyanin was isolated from a genomic bank of Paracoccus denitrificans by using a synthetic oligonucleotide. It is located directly downstream of the gene encoding the small subunit of methylamine dehydrogenase. Amicyanin is transcribed as a precursor protein with a signal sequence, typical for periplasmic proteins. Specific inactivation of amicyanin by means of gene replacement techniques resulted in the complete loss of the ability to grow on methylamine. PMID- 2261992 TI - Electron microscopy study of human myeloma immunoglobulin G1. AB - Human immunoglobulin G1 Van was studied by negative staining, freeze drying and high resolution shadow casting. The Fab and Fc subunits of an intact IgG1 molecule were shown to possess limited mobility. It was found that about 70% of molecules in the IgG1 Van specimen are not flat but have a tripod-like shape. PMID- 2261993 TI - Formylmethanofuran: tetrahydromethanopterin formyltransferase from Methanosarcina barkeri. Identification of N5-formyltetrahydromethanopterin as the product. AB - Formylmethanofuran: tetrahydromethanopterin formyltransferase was purified from methanol grown Methanosarcina barkeri to apparent homogeneity and characterized with respect to its molecular and kinetic properties. The enzyme was found to be very similar to the formyltransferase from H2/CO2 grown Methanobacterium thermoautotrophicum. It also catalyzed the formation of N5 formyltetrahydromethanopterin rather than of N10-formyltetrahydromethanopterin from formylmethanofuran and tetrahydromethanopterin. PMID- 2261994 TI - Recognition of target colloid species by conjugates of a linear polyelectrolyte with a vector protein. AB - Redistribution reaction of quaternized poly-4-vinylpyridine polycations and their conjugates with alpha-chymotrypsin by oppositely charged latex particles is disclosed. The polycations are strongly adsorbed on the latex surface. Nevertheless, they are able to migrate between the latex species via occasional interparticle contacts. In the case of a homogeneous latex such interchange results in uniform distribution of polycations by latex particles. The distribution drastically changes, when alpha-chymotrypsin-polycation conjugates interact with a mixture of two latexes: one chemically modified by bovine serum albumin and the other one by specific protein inhibitor of alpha-chymotrypsin. In this case the interchanging polycations are finally fixed on the latex particles carrying the centres of specific binding of the enzyme vector, i.e. recognize them in the latex mixture. The obtained results are considered to mimic physico chemical interaction and recognition of target supermolecular bio-objects by large macromolecules carrying relatively small molecular vectors. PMID- 2261995 TI - Cytochrome P-450LM2 oligomers in proteoliposomes. AB - The effects of bifunctional cross-linking reagents on the purified hexameric cytochrome P-450LM2 in an aqueous medium and on the proteoliposomal cytochrome P 450LM2 have been compared. In both cases, cross-linking is shown to result in the appearance of a range of additional protein bands in SDS electrophoretograms. The number and the positions of these bands seem to be similar in the solubilized and in the proteoliposomal cytochromes. No additional bands appear when the purified cytochrome P-450 was pretreated with 0.2%. Emulgen 913, which decomposes cytochrome P-450LM2 hexamers. The results indicate that the membrane-bound cytochrome P-450 can exist in the oligomeric (presumably hexameric) form. PMID- 2261996 TI - Is cytochrome P-450scc a transmembrane protein? AB - The topology of cytochrome P-450scc in the inner mitochondrial membrane of adrenal cortex has been investigated using monospecific antibodies to cytochrome P-450scc and its fragments F1 (Ile1-Arg250), F2 (Asn257-Ala481) and F3 (Asn257 Arg399). Antibodies to F1 and F2 were shown to effectively bind to the matrix and cytosolic sides of the inner membrane. Antibodies to F3 specifically interacted only with the matrix side of the membrane. These data are consistent with a model of molecular organization which shows that cytochrome P-450scc is a transmembrane protein, both N- and C-terminal sequences of the cytochrome being able to span the membrane. PMID- 2261997 TI - Sulphation of hirudin in BHK cells. AB - Hirudin, a thrombin inhibitor of the leech, was expressed in BHK cells; the alpha 1-antitrypsin signal peptide was used to direct secretion into the culture medium. The recombinant hirudin so produced inhibited thrombin and was shown by labelling experiments with [35S]sulphate to have been posttranslationally modified. PMID- 2261998 TI - Bidirectional promoter activity of the 5' flanking region of the mouse thymidine kinase gene. AB - The 5' flanking region of the gene coding for cytoplasmic thymidine kinase (TK) in the mouse (a total of 490 bp upstream of the initiation codon) was tested for promoter activity using the chloramphenicol acetyltransferase gene as reporter. It was found that the region can be divided into two parts, one of which carries promoter activity in the direction of TK, whereas the 5'-half has promoter activity in the opposite direction. A fragment of 140 bp was sufficient for growth-dependent promoter activity in the direction of TK, although about 100 bp further upstream, enhanced the activity. Expression from the divergent promoter was independent of cell growth. PMID- 2261999 TI - Subcloning and nucleotide sequence of the 3,4-dihydroxyphenylacetate (homoprotocatechuate) 2,3-dioxygenase gene from Escherichia coli C. AB - A cloned gene encoding the Escherichia coli C homoprotocatechuate (HPC) dioxygenase, an aromatic ring cleavage enzyme, was used to produce large amounts of the protein. Preparations of E. coli C HPC dioxygenase, whether expressed from the cloned gene or produced by the bacterium, lost activity very rapidly. The pure protein showed one type of subunit of Mr 33,000. The first 21 N-terminal amino acids were sequenced and the data used to confirm that the open reading frame of 831 bp, identified from the nucleotide sequence, encoded HPC dioxygenase. Comparison of the derived amino acid sequence with those of other extradiol and intradiol dioxygenases showed no obvious similarity to any of them. PMID- 2262000 TI - Do the major human glutathione S-transferases have fatty acid ethyl ester synthase activity? AB - Two fatty acid ethyl ester (FAEE) synthase isoenzymes purified from human myocardium were reported to be glutathione S-transferases (GST) [(1989) Proc. Natl. Acad. Sci. USA 86, 4470-4473; and (1989) J. Clin. Invest. 84, 1942-1946]. In the present study, the FAEE synthase activity of several purified and well characterized human GSTs were examined with ethanol and [14C]oleic acid as substrates. Three isoenzymes, GST1, GST2 and GST3 which are members of the evolutionary classes mu, alpha, and pi, respectively, were studied and failed to show any significant synthesis of FAEE after 45 min incubation at 37 degrees C. FAEE synthase activity and GST3 activity in human placental extracts can be readily separated by ion exchange chromatography on DEAE cellulose. Thus the results show that FAEE synthase activity is not a feature of the major GSTs found in human tissues. The two FAEE synthase isoenzymes isolated by Bora et al. may have been co-purified with GST isoenzymes or these FAEE synthases may be members of the GST super family that have low specific activity in conventional GST assays and have not been previously described. PMID- 2262001 TI - Purification and characterization of a chymotrypsin Kunitz inhibitor type of polypeptide from the venom of cobra (Naja naja naja). AB - A chymotrypsin Kunitz inhibitor type of polypeptide has been isolated from the venom of Naja naja naja by reverse phase HPLC and cation exchange FPLC. It is present in a considerably lower amount than that of the corresponding trypsin inhibitor. The primary structure, determined by sequence analysis of the whole molecule and its tryptic peptides, has 57 residues with an apparent molecular mass of 6.2 kDa. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. Of residues considered functionally important in Kunitz-type inhibitors, Gly-36 is replaced by Ser in a segment of weak contacts with the protease. PMID- 2262002 TI - Bacterial expression of human muscarinic receptor fusion proteins and generation of subtype-specific antisera. AB - A family of five muscarinic acetylcholine receptor genes (m1-m5) encode highly related proteins; however, for methodological reasons it has not been possible to detect the gene products individually. To develop antibody probes specific for the receptor subtypes, unique regions of m1-m5 cDNAs, corresponding to the third cytoplasmic (i3) loops, were subcloned into bacterial expression vectors and the fusion proteins expressed in E. coli were used to generate rabbit antisera. These antisera react specifically with the respective fusion proteins on immunoblots and selectively immunoprecipitate each of the native cloned receptors. Since the i3 loops are immunogenic and the epitopes in the cloned receptors are accessible to antibodies, this approach should be valuable for immunological studies of the native receptors. PMID- 2262003 TI - Catecholamines inhibit steroidogenesis by cultured porcine thecal cells. AB - The ovaries of many species contain catecholamines and beta-adrenergic receptors. The present studies were done to determine if catecholamines play a role in the regulation of androgen production by porcine theca cells. Basal and luteinizing hormone (LH)-stimulated androstenedione production was significantly inhibited by noradrenaline and isoproterenol. The inhibitory effects were dose-dependent and were enhanced when the cultures contained the carboxy-O-methyl transferase inhibitor, U-0521. The inhibitory effect of isoproterenol was reversed by the beta-adrenergic antagonist, metoprolol. Isoproterenol caused a generalized inhibition of LH-stimulated steroidogenesis, decreasing the accumulation of pregnenolone, progesterone, androstenedione and estradiol in the culture medium. These studies suggest that catecholamines may be important regulators of thecal androgen production. PMID- 2262004 TI - A reversible carrier mediates the transport of malate at the tonoplast of Catharanthus roseus cells. AB - The conditions of malate transport were defined in tonoplast vesicles purified from a microsomal homogenate of Catharanthus roseus cells by preparative free flow electrophoresis. Isolated vesicles exhibited malate transport when the membranes were prepared by grinding the cells in a homogenisation medium only buffered in the acidic pH range. By using vesicles energized artificially by an imposed pH gradient (acid interior), it was shown that malate is actively accumulated in response to the generation of a proton-motive force. Several lines of evidence (saturation kinetics, action of malate analogs and protein modifiers) support the concept that malate transport is mediated by a protein carrier which could be implicated in the uptake process as its protonated form. The malate transported in the vesicles was released by lowering the external malate concentration. The release was prevented by the anion transport inhibitor DIDS indicating the reversibility of the carrier. PMID- 2262005 TI - Rapid method for construction of yeast artificial chromosome human DNA libraries involving the trapping of cells in agarose films. AB - A simple method for the molecular cloning of fragments of more than one hundred kilobase pairs of exogenous DNA, by the encapsulation of cells in agarose beads, was reported previously for the construction of a human genomic DNA library in a yeast artificial chromosome (YAC) vector (in situ YAC construction) [1]. The efficiency of this procedure is impaired by the step in which agarose beads that contain human DNA fragments are melted before transformation. The incomplete solubility of the ligated human DNA fragment-YAC vector often results in lower than desirable frequencies of transformation. To overcome this problem we have developed a new improved method that involves use of an agarose film. The technical manipulations involved in the construction of clones of very large segments of human DNA are discussed. PMID- 2262006 TI - Purification and characterization of CMP-NeuAc:GM1 (Gal beta 1-4GalNAc) alpha 2-3 sialyltransferase from rat brain. AB - A CMP-NeuAc:GM1 alpha 2-3 sialyltransferase (GD1a synthase, 2.4.99.2) has been purified from the Triton extract of rat brain. The enzyme was purified and resolved by affinity chromatography on CDP-Sepharose column by a linear NaCl gradient elution. Final purification was achieved by elution from a 'GM1-acid' Sepharose column. SDS-PAGE of the enzyme revealed a single protein band with an apparent Mr 44 kDa. It catalyzed specifically the sialylation of GD1b, GM1 and asialo-GM1. Enzyme products were identified by TLC in three different solvent systems. The Km value for GM1 was 7.5 x 10(-2) M, and for CMP-NeuAc it was 6.5 x 10(-5) M. PMID- 2262007 TI - The platelet-derived growth factor isomers, PDGF-AA, PDGF-AB and PDGF-BB, induce contraction of vascular smooth muscle cells by different intracellular mechanisms. AB - The effect of human recombinant platelet-derived growth factor (PDGF) isoforms, (r)PDGF-AA, PDGF-AB and PDGF-BB, on contractility of rat aortic rings as well as on intracellular free Ca2+ ([Ca2+]i), intracellular pHi (pHi) and thromboxane A2 (TXA2) formation in cultured vascular smooth muscle cells (VSMC) was examined. PDGF-BB behaved similar to PDGF-AB and both have features characteristic of conventional vasoconstrictor-agonists that directly increase [Ca2+]i, activate the Na+/H+ exchanger, stimulate the TXA2 formation, and induced contraction in VSMC whereas PDGF-AA induced contraction without increasing of [Ca2+]i, pHi, and TXA2 formation. PMID- 2262008 TI - An inhibitor of protein synthesis initiation from Alhagi kirgisorum S. AB - Polyproanthocyanidin--a plant phenolic compound from Alhagi kirgisorum S. effectively inhibited protein synthesis in rabbit reticulocyte and wheat germ cell-free systems. Poly-proanthocyanidin inhibited translation only at the level of initiation and not at the elongation level and aminoacylation of tRNA. The inhibitory effect of the phenolic compound is due to the blockage of the ternary complex formation of eIF-2 with GTP and initiator Met-tRNA. PMID- 2262009 TI - [Comparative study of the fissure sealants Concise and Delton]. AB - In the case of Concise after one year 88.3% and after two years 72.8% caries prophylactic effect was measured. In case of Delton the same values were 83.8% and 89.4%, respectively. PMID- 2262010 TI - [Restoration of unilateral borderline edentulousness (Fabian-Fejerdy prosthetic class 2A-2B)]. AB - A frequent case of unilateral row and edentulousness is when, on one side, all three molars are missing and, thus, the second promolar is the last tooth. To solve such edentulousness a removable denture or a combined fix plus removable plate denture is suggested. By employing the principles of the prosthetical classification (Fabian-Fejerdy) the justification of the distally free end bridge is proved. PMID- 2262011 TI - [The role of the preschool nurse in dental caries prevention by fluorides]. AB - The education for a healthy way of living is a substantial part of the "Nursery Home Educational Programmes". Execution of infant dentistry preventive measures (accustoming to mastication, teaching of tooth cleaning, systematic tooth cleaning, distribution of Dentocar tablets) can well be fitted into the programme. PMID- 2262012 TI - Combined effect of an essential fatty acid-deficient diet and iron levels on lipid peroxidation in inflamed rats. PMID- 2262013 TI - 'Threshold effect' of increasing tocopherol ingestion upon the microsomal epoxide hydrolase activity of rat liver. PMID- 2262014 TI - Combined effect of a PUFA deficient diet and iron levels on lipid peroxidation induced by CCl4. PMID- 2262015 TI - Implication of membrane functions in toxicology. AB - The following are defined: the structural and biochemical characteristics of the membrane constituents involved in the functional activity; the importance of the environment of the proteins in the expression of their activity; and the adaptation possibilities of the membrane's functions to the nutritional distortions or to the action of drugs. The membrane's functions, as a hydrophobic barrier and its essential activities, are analysed in relation to their involvement in toxicology with examples of substances having a great specificity of action. On the other hand, the case of substances impairing, in a non-specific way, the membrane's functional state, very frequently the case in food toxicology, is analysed through the modification of the hydrophobic interaction forces that they induce. Two membranes playing a key role in food toxicology are especially studied: the enterocyte brush border, of which the essential function is absorption and which represents the first barrier to the component brought by food; and the smooth endoplasmic reticulum, which counts among its essential functions the detoxication of xenobiotics and the control of cytoplasmic Ca2+ concentration. The consequences on these functions of a change of the membrane's molecular interaction forces under the in vitro action of a series of substances having different lipophilic power (n-aliphatic alcohols, N-phenyl carbamates, methoxybenzene derivatives) are presented. The consequences of nutritional distortions (ethanol administration or diets deficient in essential fatty acids) on the in vivo adaptation of these membranes under conditions which also modify the membrane interaction forces are also considered. PMID- 2262016 TI - The toxicological significance of xenobiotic metabolism. PMID- 2262017 TI - Nutritional toxicology: basic principles and actual problems. AB - Nutritional toxicology is a specialty that combines the backgrounds and research approaches of nutrition and toxicology. Many problems of substantial importance to health and food safety involve interactions of nutrition process and requirement with the effects of toxicological impact. Solution of these problems requires research that meets the procedural and design criteria of experimental nutrition and these of experimental toxicology. The relationships may be described in three basic categories: (1) influence of nutrition on toxicities; (2) influence of toxicants on nutrition; and (3) toxicities of nutrients. Trypsin inhibitor research, an example of diet impacting on toxicological response, illustrates the necessity of controlling nutritional composition aspects that can confound the results. Prolonged acetaminophen administration provides an example of the effects of toxicants on nutritional requirement and function which could be important for persons with marginal sulphur amino acid intake. PMID- 2262018 TI - Cytoprotective effects of Gypsophila saponins towards isolated rat hepatocytes. AB - Saponins are glycosides widely distributed in the plant kingdom and are found in many foods. The hepatoprotective potential of glucuronogypsogenin (GG) and gypsoside (GY) towards isolated rat hepatocytes treated by three toxic models used at sub-lethal doses: galactosamine (5 x 10(-3) M), CCl4 (5 x 10(-4) M) and erythromycin (5 x 10(-4) M) was investigated. Two schedules were carried out corresponding to curative or preventive treatment. No protection was observed on hepatocytes treated with GY before or after addition of the toxicants. In contrast, a protective action was detected when hepatocytes were pretreated with GG (5 x 10(-5) M) as probe, by the normalisation of LDH leakage and ATP content. It depends on the toxicant: the cytoprotective spectrum is 5 x 10(-5) to 5 x 10( 7) M with galactosamine; 5 x 10(-5) to 5 x 10(-6) M with CCl4; and around 5 x 10( 5) M with erythromycin. Taking into account the importance of LDH as an indicator of membrane damages, GG was assumed to interact with membrane hepatocyte. PMID- 2262019 TI - Nutrition and membrane function: dietary vitamin A status and drug metabolism enzyme activities interactions. PMID- 2262020 TI - Correction by dietary linoleic acid of rat adipocyte metabolic disorders in essential fatty acid deficiency. PMID- 2262021 TI - Impairment of mitochondrial membrane by ethanol and protective effect of a thiazolidine compound in in vitro and in vivo experiments. PMID- 2262022 TI - Effects of lipids on cytochrome P-450 dependent B(a)P monooxygenase activity in a reconstituted system. PMID- 2262023 TI - In vitro kinetics of the oxidative reactivity of nitrate and nitrite in the rat erythrocyte. AB - Isolated rat erythrocytes were incubated in the presence of nitrate and nitrite. Glucose, lactate, reduced glutathione, methaemoglobin, malondialdehyde and Na+/K+ membrane exchange were investigated. Nitrite induced a strong methaemoglobinaemia and a net depletion of reduced glutathione in the intracellular medium associated with membrane lipid peroxidation. This oxidative reactivity induced by nitrate and nitrite altered the cell's ionic flux. PMID- 2262024 TI - Ethanol-lead interaction in the Sprague-Dawley rat. PMID- 2262025 TI - Metabolism of chlorpropham by adult rat hepatocytes co-cultured with a liver epithelial cell line. PMID- 2262026 TI - Potential toxicity of presumably insoluble aluminum salts in presence of common dietary acids. AB - It has recently been shown that aluminum absorption may occur following the administration of oral aluminium-containing phosphate-binders and antacids. Computer simulations based on relevant aluminium complex equilibria have been used in the present work to investigate the potential influence of the simultaneous ingestion of common dietary acids on this phenomenon. It results from these studies that aluminium absorption may be favoured to various extents in the presence of citric, malic, oxalic, succinic and tartric acids. PMID- 2262027 TI - Dietary polyunsaturated fatty acid deficiency: consequences for Ca2+ transport by hepatic microsomal membranes in relation with their physicochemical state. PMID- 2262028 TI - Effect of vitamin A deficiency on the in vitro transfer of mannose and N acetylglucosamine in rat liver nuclei. AB - Liver nuclei, prepared from normal and vitamin A-deficient rats, were incubated in the presence of GDP-(14C)mannose or UDP-N-acetyl(14C)glucosamine and the labelled glycoproteins analysed by SDS PAGE. Fluorographic analysis has shown that (14C) mannose labelling is enhanced by vitamin A deficiency whereas N acetyl(14C)glucosamine transfer remains approximately at the same level regardless of the vitamin A status; we did not notice any modification when the proteins were monitored by Coomassie blue or by silver nitrate. PMID- 2262029 TI - Monensin and 14C oleic acid absorption in the rat. PMID- 2262030 TI - Inhibition of ethoxyresorufin deethylase activity by natural flavonoids in human and rat liver microsomes. AB - Several flavones and flavonols (chrysin, quercetin, luteolin, flavone and 7, 8 benzoflavone) were found to inhibit ethoxyresorufin deethylase (EROD) activity in human and rat liver microsomes. In man, molecules without hydroxyl groups are more powerful inhibitors than polyhydroxylated flavonoids (7, 8-benzoflavone greater than flavone greater than chrysin greater than luteolin greater than quercetin greater than morin). In rat, chrysin was the strongest inhibitor and the less effective were morin and 7,8-benzoflavone. For all molecules human microsomes were more sensitive than rat microsomes. The most important difference concerned 7,8-benzoflavone which was 10,000-fold more potent in man. PMID- 2262031 TI - Free radical inhibitor effect of retinol after carbon tetrachloride intoxication in the rat. AB - A study was conducted to explore the free radical inhibitor effect of retinol in Male Wistar rats. When retinol-deprived animals were considered retinol-depleted (after a period of 8 weeks), rats of each group, control and depleted, received an intraperitoneal injection of mineral oil (5 ml/kg body weight) or an equivalent volume of 20% carbon tetrachloride (CCl4) dissolved in mineral oil. The animals were killed by decapitation 4 h after administration of CCl4 and liver, heart, spleen, brain and testes were quickly removed. Minced tissues were homogenized and microsomes were prepared; vitamins A and E were monitored and malondialdehyde (MDA) content was estimated. Retinol-depleted rats showed an hepatic vitamin A level less than 10 pmol/mg protein, compared to control rats (15-45 pmol). In all hepatic preparations, we found low vitamin E levels (100 1300 pmol/mg protein). MDA production increased significantly in livers and hearts of retinol-depleted rats but not in brains, spleens and testes. Hearts contain less lipids and vitamin E than these latter organs, which could correlate with the highest production of MDA. PMID- 2262032 TI - Industrial requirements in food safety. AB - The principles of establishing industrial requirements in food safety are described, taking risk potentials all along the food chain into their respective account. Regulations will, in the future, lead to increased autocontrol in production. The rapid changes in food technology require constant adaptation to new problems, to keep the global quality of food at a high level. Regulatory authorities will, in the new European market, concentrate on enforcement of 'essential requirements' while industrialists will follow good manufacturing practices. Open dialogue between the latter, the former and the scientific community is highly desirable since mutual knowledge of the problem will help maintain a high level of food safety, for the benefit of everybody. PMID- 2262033 TI - Ecotoxinogenesis of Pithomyces chartarum. AB - Facial eczema is a hepatogenous photosensitivity mycotoxicosis resulting from sporidesmin ingestion. The morphological characters of toxigenic strains of P. chartarum are reported and the effect of temperature on growth and mycotoxin production are studied. The temperature range for which there is an actual risk of toxin accumulation (20-25 degrees C) is much narrower than for an appreciable growth (5-30 degrees C). PMID- 2262034 TI - Lead, cadmium and chromium content of edible vegetables grown in three different agricultural areas. PMID- 2262035 TI - Action of phosphine (PH3) on production of sterigmatocystin by various fungal strains isolated from foodstuffs. AB - Phosphine is a food fumigant, used until now as an insecticide and rodenticide. The present work researches the action of phosphine treatment on growth and sterigmatocystin production of several fungal strains. Production of sterigmatocystin decreased by a ratio of 100 to 500 or was abolished. PMID- 2262036 TI - Aldicarb residues in citrus soil, leaves and fruits. AB - Aldicarb was applied to the soil of Late Valencia orange field plots. A comparative study between four analytical methods is reported, the NPD-gas chromatography method being the best choice. The work also reports the study of accumulation and persistence of aldicarb and its biologically active metabolites in the soil, leaves and fruits (rind and pulp, separately). Residue content, at the ppb level, was found in the order leaves much greater than rind greater than pulp. Carbamate was found to accumulate mainly in its oxidized forms. Residues had reached a maximum level in about 90 days after application. PMID- 2262037 TI - Free malondialdehyde determination by HPLC applied to microsomal studies. AB - Malondialdehyde (MDA) is a product of lipid peroxidation in vivo. The most widely employed method for determination of free MDA is based on its reaction with thiobarbituric acid (TBA) which produces a pink pigment with an absorption maximum at 532-535 nm. However, quantitation of MDA is limited by its lack of specificity and a high performance liquid chromatographic (HPLC) method was recently developed in several laboratories. In the present study, free MDA levels were measured, after TBA reaction, spectrophotometrically and by HPLC in microsomes of different tissues from rats fed a vitamin A-deficient diet or not for 8 weeks, and treated or not with carbon tetrachloride. Incubation in vitro with NADPH (0.25 mM) or ascorbate (0.50 mM) in the presence of Fe2+ (5 microM) ADP (0.5 mM), allowed us to estimate the total amount of enzymatic or non enzymatic lipoperoxidation. The MDA amount determined by HPLC is significantly lower than the TBA-reactive substances (TBA-RS) calculated spectrophotometrically as MDA equivalents. Moreover, HPLC separations performed on a mu Bondapack C18 column with a mobile phase of methanol/water 45/55 (v/v), containing 1% cetrimide revealed that three chromogens are present in microsomes incubated with ascorbate or NADPH. The TBA-RS visible spectra of microsomes incubated with activator are complex with an absorption maximum at 533 nm, which is specific for the MDA-TBA chromogen, and one at 450 nm. Identification of these TBA-RS, different from the MDA-TBA complex, is under investigation in our laboratory. PMID- 2262038 TI - Oxidants and antioxidants in carcinogenesis. PMID- 2262039 TI - Mutagenesis and micronutrients relationship. AB - Several micronutrients have been reported to be mutagenic or co-mutagenic in certain in vitro testing systems. However, micronutrients have not been shown to be mutagenic or co-mutagenic in vivo, or at physiological concentrations in vitro. Most of the mutagenic or co-mutagenic effects of micronutrients observed in vitro can be attributed to their involvement in the generation of oxygen radicals. Many micronutrients have been shown to possess anti-mutagenic or co antimutagenic activity in vitro and in vivo. This property of micronutrients appears to be linked to their specific and interrelated biochemical functions. PMID- 2262040 TI - Epidemiological aspects in food safety. AB - The rapid growth of international trade in food products has resulted in increased hazards from trans-boundary foodborne infections and intoxication. Therefore, the development of multinational surveillance and registration of foodborne diseases or food contamination, of both biological and chemical origin, is of utmost importance for their prevention and control. Recognizing the importance of accurate and adequate epidemiological data for decision making with respect to priorities, resources and management, the World Health Organization (WHO) launched in 1976 the Joint UNEP/FAO/WHO Food Contamination Monitoring Programme (GEMS/Food) and in 1980 the surveillance programme for control of foodborne infections and intoxications in Europe. Although the response of participating countries in both programmes was very positive, many questions have arisen during this period which require further improvements through national and international action. Monitoring and surveillance of food contamination and foodborne infections and intoxications is a multidisciplinary process and requires the active involvement of experts in medical and veterinary food hygiene, food chemistry and epidemiology. Since health risk management with respect to food safety is frequently delegated to different authorities, much better coordination between the sectors is needed in order to improve epidemiological analysis at national and international level. The purpose of this paper is to review the WHO regional programme for prevention and control of foodborne infections and intoxications in the light of accumulated experience and to discuss plans and possibilities for further improvements through national and international action in the 1990s. PMID- 2262041 TI - Methionine dependence of rat hepatocarcinoma cells in culture: relationship with tumourigenicity and oncogene expression. AB - The culture in methionine-deprived medium of a rat hepatoma cell line (LF) significantly decreases: (1) the growth in vitro of these cells; (2) their tumourigenicity; and (3) the expression of a panel of oncogenes. When the LF cells are replaced in a medium containing methionine, they maintain a diminished in vitro growth and tumourigenic capacity, despite an overexpression of the same oncogenes. These data point out the determinant role of a nutritional factor, methionine, in tumour growth. PMID- 2262042 TI - Effects of bioactivation inhibitors on covalent binding of 2-AAF to rat liver DNA in vivo and on hepatocytes cultures. PMID- 2262043 TI - The effect of dietary retinyl palmitate on the retinyl ester content of human or rat liver tumours. PMID- 2262044 TI - GALT involvement in food allergy. PMID- 2262045 TI - Immunosuppressive effects of four trichothecene mycotoxins. AB - The trichothecenes are a family of mycotoxins contaminating some food and feeds. We have studied the inhibitory effect of four of them including less toxic compounds: T-2 toxin, DAS, DON and Trichodermin, on normal human peripheral blood lymphocytes and murine splenic lymphocytes. The results show that even for the least toxic compound, inhibiting concentrations can be realised in the blood by common alimentary contamination. PMID- 2262046 TI - Expression of Ca2+ mobilizing receptors in Xenopus oocytes: a tool for receptor characterization. AB - In order to investigate the molecular characteristics of gastrointestinal hormone receptors, we have expressed their mRNAs in Xenopus laevis oocytes. Xenopus oocytes possess intrinsic muscarinic cholinergic receptors which couple to intracellular Ca2+ release. Release of intracellular Ca2+ was detected by an increase in 45Ca2+ release from preloaded oocytes or by using the Ca2+-sensitive fluorescent dye fura-2. Similarly, cholecystokinin (CCK) receptors expressed on the surface of oocytes which were injected with mRNA prepared from rat pancreatic acinar AR42J cells were readily detected by their ability to mobilize intracellular Ca2+. The CCK receptors expressed in oocytes showed similar binding characteristics as the native receptors. CCK receptor expression in the oocytes could be specifically blocked by hybridizing the mRNA with antisense oligonucleotides based on the highly conserved second transmembrane region of the HM4 muscarinic cholinergic receptor before injection. These latter results strongly suggest that the CCK receptor is a member of the G protein-linked receptor family. Thus, expression in Xenopus laevis oocytes provides a powerful tool for elucidation of the molecular characteristics of gastrointestinal hormone receptors. PMID- 2262047 TI - Ulceration induces a novel epidermal growth factor-secreting cell lineage in human gastrointestinal mucosa. AB - Ulceration anywhere in the gastrointestinal tract induces a novel cell lineage, which grows from the bases of existing crypts, ramifies to form a new gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, and secretes abundant immunoreactive epidermal growth factor/urogastrone (EGF/URO). All gastrointestinal stem cells can produce this cell lineage following mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal ulceration, and we propose that a major in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut via induction of this cell lineage in the adjacent mucosa. EGF/URO should therefore be assessed in the conservative management of inflammatory bowel disease. PMID- 2262048 TI - Effect of diabetes in the BB Wistar rat on the peptidergic component of the enteric innervation. AB - Whole mount preparations of the small intestine from Wistar, normoglycemic 90-day diabetic BB, hyperglycemic 90-day diabetic BB and age-matched nondiabetic BB rats were immunostained to determine the extent of the peptidergic innervation. The neuropeptides examined were vasoactive intestinal peptide, neuropeptide Y, substance P. calcitonin gene-related peptide, galanin and somatostatin. The extent of the peptidergic innervation in the submucous and myenteric plexuses from the control Wistar, nondiabetic BB and normoglycemic diabetic BB rats was identical. In the submucous plexus of the hyperglycemic diabetic BB rats there was a marked reduction in the number of somatostatin-immunoreactive neurons and nerve fibres. Substance P and calcitonin gene-related peptide which are colocalized in a proportion of the somatostatin neurons were unaffected. In the myenteric plexus of the hyperglycemic diabetic BB rats the number and intensity of staining of the galanin-immunoreactive nerve fibers was markedly increased. Galanin has not been observed to colocalize with any of the other neuropeptides examined. PMID- 2262049 TI - Regulation of proliferation by fibroblast growth factor in a pancreatic cancer cell line. AB - Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. We report here the first study of the effects of bFGF on a digestive tract derived cell line. The effect of bFGF on the proliferation of AR4-2J cells, tumor cells of acinar pancreatic origin, was investigated together with modulation of ornithine decarboxylase (ODC) activity, an intracellular event involved in cell proliferation. bFGF caused a concentration-dependent stimulation of AR4-2J cell growth, with a half maximal effect (EC50) at 22 +/- 2 pM. ODC activity, assayed by the CO2-trapping method, was also increased by bFGF in a dose-dependent manner, reaching half-maximal stimulation at 20 pM. We conclude that bFGF is a very potent growth promoting factor for cells of pancreatic origin, already effective at picomolar concentrations. The parallelism between the growth assay and the ODC activity assay implicates the involvement of ODC activity in the pathway of the mitogenic effect of bFGF. The stimulation of ODC activity therefore seems to be a reliable early marker for cell proliferation in this model. PMID- 2262050 TI - Gastrin modulates growth of a rat acinar pancreatic cell line: receptor analysis and signal transduction. AB - Recent studies have demonstrated the presence of both CCKA and CCKB receptors on dog and guinea pig pancreas. Although CCKA receptors are implicated in enzymatic secretion, biological effects of CCKB receptors are still unknown. We have previously found that a rat acinar pancreatic cell line (AR4-2J) possesses both receptor subtypes. In this work we report the ability of various CCK/gastrin agonists and antagonists to bind with these receptors. We found that gastrin, pentagastrin and Gastrin/CCK4 induce ornithine decarboxylase activity, an early event involved in cell proliferation, as well as 3H-thymidine incorporation. Furthermore, these effects occur at doses at which these peptides interact only with the CCKB receptor subtype. In view of these data we propose that modulation of AR4-2J cell growth by gastrin agonists specifically involve occupation of the CCKB receptor. PMID- 2262051 TI - Effects of an inhibitor isolated from human small intestine on organ culture of intestinal mucosa. AB - Endogenous mitotic inhibitors have been implicated as controlling mechanisms of intestinal epithelium proliferation. We previously reported the purification of an inhibitor of intestinal epithelial cells in culture isolated from a villous extract of human jejunum. This article describes the biologic effects of this inhibitor on organ cultures of rabbit intestinal mucosa. Our results reveal that (1) this factor is not cytotoxic; (2) it inhibits intestinal epithelial cell proliferation in a dose-dependent and reversible manner; (3) it does not appear to be species-specific; (4) it is specific to the digestive tract, and more particularly to the small intestine. PMID- 2262052 TI - Contribution of neurotensin to the entero-pancreatic axis. AB - Plasma neurotensin concentrations are markedly elevated in patients with severe exocrine pancreatic insufficiency. We therefore investigated whether the exocrine pancreatic function could influence postprandial neurotensin plasma concentrations. Subsequently, we tested the hypothesis that this peptide hormone is involved in regulation of pancreatic secretion. When pancreatic juice is diverted from modified Herrera fistulas in dogs, a simultaneous application of physiological amounts of lipase reduces the elevated plasma neurotensin concentrations. On the other hand, immunoneutralisation of the circulating neurotensin inhibits pancreatic secretion. This suggests a physiological role of neurotensin in the regulation of the exocrine pancreas via an entero-pancreatic axis. PMID- 2262053 TI - Molecules of the extracellular matrix: potential role of collagens and glycoproteins in intestinal adaptation. AB - The extracellular matrix plays a fundamental role in modulating cellular growth, differentiation and migration. Therefore it merits major attention in studies of adaptation. The five types of collagen and several extracellular glycoproteins hitherto found in the intestine are biochemically well defined. They form supramolecular complexes and via specific domains interact with integrins, a specialized class of transmembrane glycoproteins. The integrins transfer signals to the cytoskeleton and probably to the nucleus of the cell. The extracellular matrix and its cellular receptors are well orchestrated with several cell types, the immune system and soluble mediators and hormones, thus being indispensable members of a complicated regulatory network operative in adaptation. PMID- 2262054 TI - Direct vs. indirect effects of bombesin on pancreatic growth. AB - Bombesin and its mammalian analogue gastrin-releasing peptide (GRP) have been reported to stimulate pancreatic growth. Whether this stimulatory effect is mediated through the release of regulatory peptides, in particular CCK, remains controversial. Since CCK is the most potent stimulant of pancreatic growth, it is a potential mediator of bombesin-induced pancreatic growth. On the other hand, there is evidence from in vitro studies, supporting a direct interaction of bombesin with receptors on acinar cells. A number of studies using potent and selective CCK antagonists have revealed controversial results. This may in part be due to considerable differences in their design and methods. The recent development of potent bombesin antagonists provides an important tool to further characterize the mechanism of bombesin-induced pancreatic growth and to determine the physiologic importance of bombesin. PMID- 2262055 TI - Effects of long-term CCK stimulation and CCK blockade on pancreatic and intestinal growth, morphology, and function. AB - This study evaluated the effects of long-term cholecystokinin (CCK) stimulation and blockade on pancreatic and intestinal growth, function, and morphology. CCK release was induced by feeding of the protease inhibitor camostate and CCK blockade by feeding of the CCK antagonist CR 1409. Four groups of NMRI-mice received the following diets for 9 months (each group consisting of 36 mice): (1) chow (control); (2) chow + 100 mg/kg/day camostate; (3) chow + 50 mg/kg/day CR 1409; (4) chow + 100 mg/kg/day camostate + 50 mg/kg/day CR 1409. Long-term feeding of camostate greatly increased pancreatic weight by induction of marked hypertrophy (increase in protein content) and moderate hyperplasia (increase in DNA content). Camostate feeding also increased secretory capacity of the exocrine pancreas. Despite camostate-induced growth neither hyperplastic nor neoplastic nodules developed. The CCK-antagonist CR 1409 markedly inhibited the effects of camostate which are therefore mainly mediated by CCK. Neither long-term CCK stimulation nor CCK blockade altered morphology or composition of duodenal mucosa. Feeding of CR 1409 alone (i.e., without camostate) slightly but significantly decreased pancreatic content of protein and secretory capacity of enzymes when compared to the chow-fed control; pancreatic weight and DNA content remained unchanged after long-term administration of CR 1409. Thus, long-term, continuous and effective blockade of the CCK-receptor only slightly inhibited pancreatic growth and secretory capacity. CCK is, therefore, not an essential growth factor for the pancreas, although increases of endogenous CCK stimulate pancreatic growth and secretory capacity. PMID- 2262056 TI - Pancreatic spasmolytic polypeptide, a potential growth factor for the intestine: neural control of secretion. AB - We studied the effect of electrical stimulation of the vagus nerves and the effect of vasoactive intestinal polypeptide (VIP) on the secretion of pancreatic spasmolytic polypeptide (PSP) from isolated perfused porcine pancreas. We measured the concentration of PSP in the pancreatic juice and in the venous effluent by radioimmunoassay. The concentration in the pancreatic juice varied between 1 and 180 micrograms/ml, and in the venous effluent between 1 and 10 ng/ml. PSP is thus mainly an exocrine product. However, the concentrations in juice and venous effluent varied in parallel. Electrical vagus stimulation increased the output in the juice of PSP approximately 30 times. Atropine (10(-6) M) prevented the increase in PSP concentration during vagus stimulation, but only partially inhibited the output. VIP (10(-8) M) increased the output of PSP but decreased the concentration. We conclude from these results that PSP secretion is controlled by neural parasympathetic mechanisms that include both cholinergic and peptidergic pathways. PMID- 2262057 TI - Cholecystokinin receptor antagonist loxiglumide: influence on bilio-pancreatic secretion and gastrointestinal hormones in man. AB - We characterized the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output and plasma CCK concentrations determined by radioimmunoassay and bioassay. Gallbladder emptying and bilirubin output in response to the intraduodenal administration of a mixed liquid meal were completely inhibited by an intravenous infusion of loxiglumide (10 mg/kg/h). In contrast, meal-stimulated pancreatic enzyme secretion was diminished by only 30-40%. CCK concentrations in response to the test meal were 3-fold higher during infusion of loxiglumide, as determined by radioimmunoassay. In the absence of the antagonist, the bioassay measured CCK plasma levels identical to those determined by radioimmunoassay. In the presence of loxiglumide, CCK-like bioactivity was not detectable, indicating that the plasma concentrations of the CCK receptor antagonist were sufficient to abolish all circulating CCK-like bioactivity. We conclude that fasting volume and meal induced contraction of the gallbladder are controlled by CCK. Postprandial pancreatic enzyme secretion, however, is mainly mediated by non-CCK-dependent mechanisms. Plasma CCK-like immunoreactivity is increased by loxiglumide, whereas plasma CCK-like bioactivity is zero in the presence of an CCK-receptor antagonist. PMID- 2262058 TI - The immune system and mucosal transformation--historical perspective. AB - An intimate association between columnar epithelial cells and lymphocytes within the epithelial layer of the gut and other organs has been recognised for more than a century. Various roles have been postulated for intraepithelial lymphocytes (IEL), nutritive as well as immunopathological. Recently, the relevance of activation of mucosal lymphocytes to some of the development changes in the gut at weaning have been hypothesised, and the relevance of the IEL to the induction of specialised epithelium overlying Peyer's patches remains to be established. Interactions between lymphocytes and the structure of the gut mucosa can readily be studied by using defined animal models in which the state of development of the gut, luminal antigens and bulking agents, host factors such as nutritional status can be defined, and against such background various forms of immune-mediated intestinal injury can be created. The earliest work along these lines was purely descriptive, particularly of the weaning changes, and also concerned the lymphocyte mediated gut damage of allograft rejection and later other models of T cell injury. These experiments clearly showed stimulation of crypt mitosis in immune mediated enteropathy, with crypt hyperplasia, which could not be explained by a feedback stimulation from damaged villi or villus enterocytes. Further work is now showing that mediators released by lamina propria activated T cells influence mitotic activity and differentiation of crypt enterocytes, as well as modifying the rate and patterns of expression of brush border enzymes and expression of cell surface class II HLA antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262059 TI - Low grade B cell lymphoma of gut-associated lymphoid tissue (GALT): a model of the structure and migration pathways of the B cell component of normal human GALT. AB - The histology, microenvironment and migratory pathways of low grade B cell lymphomas (LGBL) are thought to reflect those of normal lymphoid tissue of similar lineage. Striking clinical differences between LGBL of peripheral lymph nodes and those of the gastrointestinal tract serve to emphasize the lineage differences between mucosal and non-mucosal B cells and suggest that LGBL of gut associated lymphoid tissue (GALT) could serve as a natural experimental model for the investigation of the properties of normal human GALT. The histology of LGBL of GALT parallels that of normal GALT and draws particular attention to the previously undescribed GALT marginal zone B cells which show close lineage homology with LGBL of GALT. These cells known as centrocyte-like (CCL) cells surround follicles, infiltrate the epithelium and frequently show plasma cell differentiation possibly in response to stimulation from the gut lumen. In LGBL of GALT the CCL cells have an intimate relationship with reactive follicles similar to that described for rat splenic marginal zone cells. LGBL of GALT are slow to disseminate to the periphery and can often be cured by local eradication. This suggests CCL cells do not enter the peripheral blood. However, the gastrointestinal tract remote from the primary tumour is occasionally selectively involved, a finding which supports circulation and homing as described in animals. Using a murine monoclonal anti-idiotypic antibody in one case of LGBL of GALT we have shown that CCL cells appear to enter the circulation and, in the absence of evident tumour, can be identified in the mucosae as well as the marginal zone of the spleen where they undergo plasma cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262060 TI - Special functional features of T-lymphocyte subpopulations in the effector compartment of the intestinal mucosa and their relation to mucosal transformation. AB - Recent studies indicate that intestinal lamina propria T cells are highly specialized lymphocytes, which differ from T cells in other compartments of the immune system in several respects. In the present study phenotypic and functional characteristics of lamina propria T cells and their possible relation to mucosal growth will be discussed. Lymphocytes from human and nonhuman primate intestine were isolated by an enzymatic procedure. Lymphocytes were studied using dual color immunofluorescence (FACS) and functional in vitro assays. CD4 positive (helper-) lamina propria T-cells lack the CD45RA antigen and express the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition intestinal T cells express IL-2 receptors and IL-2 receptor mRNA, and are able to synthesize high amounts of IL-2. Functional studies in nonhuman primates infected rectally with Chlamydia trachomatis have shown that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. The intestinal lamina propria therefore contains highly specialized T cells which have the phenotype of memory T cells and which are activated. Functionally these T cells can be characterized as differentiated effector lymphocytes. Recent studies from other laboratories have shown that the pattern of lymphokines produced by lamina propria T cells and the responsiveness to certain lymphokines also differ from those of other lymphocyte populations. Since T-cell-derived lymphokines are also important regulators for epithelial growth and differentiation as well as for connective tissue metabolism, lamina propria T cells might be of major importance in mucosal growth and transformation. PMID- 2262061 TI - The role of activated T cells in transformed intestinal mucosa. AB - Activated T cells can be identified immunohistochemically in the intestinal lamina propria in a number of gastrointestinal diseases including food sensitive enteropathy (coeliac disease) and intractable diarrhoea of infancy. Experimental studies have shown that T cell activation in human intestinal lamina propria in vitro produces an increase in crypt cell proliferation, villous atrophy, increased HLA-DR expression on enterocytes, increased intraepithelial lymphocyte numbers, and, phenotypically, macrophage activation. All of these features are seen in food sensitive enteropathy and it is proposed that lamina propria T cell activation to food antigens plays the primary role in the pathogenesis of these disorders by altering mucosal morphology and the rate of epithelial cell proliferation. PMID- 2262062 TI - Role of in vivo activated T cells in the mechanisms of villous atrophy in humans: study of allograft rejection. AB - Four children aged 6 months to 9 years received fully HLA-mismatched ABO identical small intestinal allografts. In order to monitor the rejection process and to study epithelial changes induced by intestinal T cells activated by an allogeneic reaction, iterative biopsies were performed through the ileal enterostomy and processed for histology and immunohistochemistry. Episodes of acute histological reaction were observed in all 4 patients between day 10 and 160. It was preceded by appearance of pericryptic CD3+CD4+ or CD8+ T cells of recipient origin, increasing numbers of which expressed CD25. Simultaneously, early epithelial changes were noted: increased HLA-DR expression by enterocytes and decreased mitotic rate as shown by decreased numbers of KI67+ cells in crypts. During acute histological rejection, massive infiltration of mucosa by CD25+CD3+ T-cells and activated macrophages (KIM6+CD25+), was associated with crypt necrosis and then, destruction of surface epithelium. Successful treatment of graft rejection episodes with antilymphocytic serum (2), anti-CD3 monoclonal antibody (2), anti-CD25 monoclonal antibody (1) resulted in a rapid decrease of CD3+ cells, a more progressive decrease of CD25+ and KIM6+ macrophages, reappearance of KI67+ cells in crypts followed after a variable delay by recovery of villous architecture. Chronic histological rejection was observed in 1 patient after 7 months. It was characterized by total villous atrophy, fibrosis, endarteritis, infiltration of lamina propria and epithelium by CD3+CD8+ cells, a small number of which CD25+, strong HLA-DR expression by crypt and surface epithelium, increased numbers of KI67 enterocytes. Altogether these data suggested that activated T cells can induce two types of villous atrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262063 TI - Mucosal atrophy is associated with loss of activated T cells in the duodenal mucosa of human immunodeficiency virus (HIV)-infected patients. AB - Gastrointestinal symptoms and malabsorption are frequent in HIV-infected patients even in the absence of opportunistic infections. In earlier studies we found indications that the gastrointestinal mucosa itself may be affected by HIV. Since there is evidence that the mucosal structure is influenced by changes in the gut associated lymphoid tissue, we have investigated mucosal structure and immune cells in HIV-infected patients. Sixty patients (3 f, 57 m; age 21-61, median 37 years; 11 at CDC stage II or III, 49 at stage IV) with gastrointestinal complaints undergoing upper endoscopy were examined for enteric pathogens. Duodenal biopsies were labelled by immunohistology for HIV antigen p24 and for lymphocyte surface markers; mucosal architecture was studied by three-dimensional morphometry. Biopsies from HIV seronegative patients without abnormal findings served as controls. In 29 patients an enteric pathogen was identified. In 22 patients HIV-infected mononuclear cells were detected in the lamina propria. In the lamina propria CD25+ cells were decreased, CD3+ and CD8+ cells were increased in HIV-infected patients compared with controls, while the numbers of CD4+, Leu8+, and HML-1+ cells, and of macrophages were not different. Patients at stage IV had decreased numbers of CD4+ T cells compared with patients at stage II or III. Villus surface area was reduced in HIV-infected patients compared with controls. Crypt depth was increased in patients with intestinal infection compared with controls while numbers of mitotic figures were normal. Patients without intestinal infection and patients with mucosal HIV-infected cells had decreased numbers of mitotic figures and normal crypt depth compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262064 TI - Relationship between survival and binding of plant lectins during small intestinal passage and their effectiveness as growth factors. AB - The effects on the small intestine and the growth of rats of six pure plant lectins: PHA (Phaseolus vulgaris); SBL (Glycine maxima); SNA-I and SNA-II (Sambucus nigra); GNA (Galanthus nivalis) and VFL (Vicia faba), covering most sugar specificities found in nature, were studied in vivo. Variable amounts, 25% (VFL) to 100% (PHA, GNA) of the lectins administered intragastrically, remained in immunochemically intact form in the small intestine after 1 h. All lectins, except GNA, showed binding to the brush border on first exposure, although this was slight with VFL. Thus, binding to the gut wall was not obligatory for resistance to proteolysis. Exposure of rats to lectins, except VFL, for 10 days, retarded their growth but induced hyperplastic growth of their small intestine. The two activities were directly related. PHA and SNA-II, whose intestinal binding and endocytosis was appreciable after 10 days of feeding the rats with diets containing these lectins and similar to that found on acute (1 h) exposure, were powerful growth factors for the small intestine. GNA, which did not bind at the start but was reactive after 10 days, and SNA-I, which behaved in the opposite way, induced changes in receptor expression in the gut. As they were bound to the brush border transiently, they were less effective growth factors. VFL was not bound or endocytosed, was non-toxic and did not promote gut growth. PMID- 2262065 TI - Polyamine metabolism. AB - Currently, two major pathways are distinguished along which the polyamines are metabolized: the interconversion pathway and the so-called terminal polyamine catabolism. In vertebrates, the interconversion pathway is a cyclic process which controls polyamine turnover. In conjunction with polyamine transport, it regulates intracellular polyamine homeostasis. In vertebrates, putrescine, the precursor of spermidine and spermine, is exclusively formed by decarboxylation of ornithine--as far as de novo synthesis is concerned. Spermidine and spermine synthase form spermidine from putrescine, and spermine from spermidine, by transfer of aminopropyl residues from decarboxylated S-adenosylmethionine. In the catabolic branch of the interconversion cycle, spermine is degraded to spermidine, and spermidine to putrescine. The first step in this sequence is acetylation in the N1 position. This is followed by oxidative splitting of the acetylated polyamines, whereby the aminopropyl residues which originated from decarboxylated S-adenosylmethionine are removed. The enzyme catalyzing this step is an FAD-dependent oxidase (polyamine oxidase). Ornithine decarboxylase, S adenosylmethionine decarboxylase, and acetyl CoA:polyamine N1-acetyltransferase are highly regulated, inducible enzymes with a high turnover rate. Depending on the physiological situation, each of these enzymes may become rate limiting. Terminal polyamine catabolism is catalyzed by Cu2(+)-dependent amine oxidases, of which only diamine oxidase has been well defined. By oxidative deamination of a primary amino group, each intermediate of the interconversion cycle can be transformed into an aldehyde, which is further oxidized to an amino acid or a gamma-lactam. The products of the terminal catabolism as well as the acetylated polyamines are urinary excretory products. In addition to intracellularly synthesized polyamines, polyamines from various tissues and from exogenous sources (such as the gastrointestinal tract) may be utilized by those tissues which have a high demand. Polyamines play a paramount role in growth processes. In order to control growth (for example of tumors), it is necessary to block all major polyamine sources. If only one source is blocked, the remaining sources are usually capable of furnishing sufficient polyamines to support growth processes. PMID- 2262066 TI - Polyamines in pancreatic growth. AB - This chapter reviews available data concerning the role of polyamines in pancreatic growth. Like in many other mammalian cells stimulation of pancreatic proliferation by trophic factors is associated with an early increase in ornithine decarboxylase (ODC) activity with consequent putrescine formation. ODC and putrescine play probably an important role in the initiation but not maintenance of pancreatic growth. The application of the specific ODC inhibitor alpha-difluoromethylornithine (DFMO) alone is not sufficient to judge the role of polyamines in pancreatic growth. For that purpose a combination of substances which inhibit ODC (DFMO) and polyamine oxidase (N1,N4-bisallenylputrescine) and/or S-adenosylmethionine-decarboxylase (SAM-DC) simultaneously has to be investigated. Ideally polyamines from dietary sources and intestinal bacterial flora should be abolished. The uptake of polyamines from the circulation has still to be considered. Studies will be presented proving that though ODC is completely inhibited by DFMO putrescine is still formed via spermidine/spermine N1-acetyltransferase (SAT). The fast increase of ODC in response to growth stimulating factors like cholecystokinin (CCK) is regulated at a pretranslational level by increasing ODC mRNA. PMID- 2262067 TI - Polyamine uptake by human colon carcinoma cell line CaCo-2. AB - The intracellular concentrations of the polyamines are highly regulated and high polyamine concentrations are associated with rapidly proliferating cells. Hormones, nutrients and growth factors that stimulate the proliferation of the intestinal epithelium, increase the intracellular polyamine concentration mainly by activating ODC expression. Other cell types stimulated to proliferate satisfy their requirement for polyamines by increasing polyamine uptake. In the present study, we investigated polyamine uptake by a human colon carcinoma cell line, CaCo-2. Uptake of putrescine, spermidine and spermine by CaCo-2 cells was saturable and temperature dependent and all polyamines appear to share a common carrier. The carrier of differentiated cells had an apparently higher affinity and lower activity than the carrier of replicating cells. Culture of CaCo-2 cells on porous filters showed that polyamine accumulation occurred mainly through the basolateral membrane in replicating cells, while an increase in the rate of apical uptake was observed after differentiation. A significant increase in polyamine uptake and in ODC expression resulted from fresh medium replacement, a well-known stimulus to proliferation; no change in uptake occurred after ODC inhibition by DFMO. We conclude that CaCo-2 cells are able to increase their polyamine concentration by both enhanced synthesis and increased polyamine uptake. PMID- 2262068 TI - Polyamine metabolism and uptake during Phaseolus vulgaris lectin, PHA-induced growth of rat small intestine. AB - Kidney bean lectin, PHA, stimulated the hyperplastic and hypertrophic growth of rat small intestine. This growth was preceded by a rapid accumulation of polyamines in the small intestine. However, since the lectin had little effect on in situ polyamine biosynthesis, most of the polyamines must have been of extracellular origin. To investigate the source of polyamines, both the luminal uptake and basolateral transport of polyamines by the rat small intestine were measured in vivo. Luminal polyamine uptake was apparently by passive diffusion, non-saturable, linearly dependent on concentration and its extent was not stimulated by PHA. In contrast, 14C-polyamines injected intraperitoneally were probably taken up by a transport system(s). Moreover, basolateral polyamine transport was stimulated in a time-dependent manner when small intestinal growth was stimulated by PHA. However, in keeping with the finding of polyamine accumulation prior to demonstrable growth of the tissue, stimulation by PHA of the polyamine transport system also preceded small intestinal growth. Stimulation of polyamine transport by luminal factors is possibly a general mechanism involved in intestinal adaptation. PMID- 2262069 TI - Acute and chronic effects of cyclosporine A on pancreatic polyamine metabolism and pancreatic adaptation. AB - The present study was designed to investigate the effects of acute and chronic application of the immunosuppressive agent cyclosporine A (CsA) on pancreatic polyamine metabolism as well as pancreatic growth of rats in vivo. Seven to ten animals per group were treated with either the synthetic trypsin inhibitor camostate (FOY-305, 200 mg/kg b.wt. p.o. twice a day), CsA (10 mg/kg b.wt. p.o. once a day), camostate plus CsA, or oil as control, and animals were killed after 8 h, 1, 5 and 14 days. Feeding of camostate resulted in a significant increase of the measured parameters in the following time-course: cholecystokinin (CCK), 8 h; ornithine decarboxylase (ODC), 8 h: putrescine, 8 h; S-adenosylmethionine decarboxylase (SAM-DC), 1 day; pancreatic weight, 1 day; protein content, 5 days; spermidine, 5 days; RNA, 5 days; and DNA, 14 days. Simultaneous treatment with CsA resulted in a significant inhibition of camostate-induced increases in ODC, SAM-DC as well as putrescine and spermidine and furthermore caused a nearly complete inhibition of the increase of all trophic parameters, while CCK plasma levels were not altered. Counterregulatory mechanisms to maintain the intracellular polyamine pool as known after application of specific inhibitors of enzymes of the polyamine metabolism (i.e. DFMO) were not observed. Therefore we conclude that CsA does not directly interact with the polyamine metabolism, but rather with the second messenger system or any other intracellular mechanism, that is activated after stimulation with CCK before the polyamine metabolism is induced. PMID- 2262070 TI - Apparent post-transcriptional modification of ornithine decarboxylase accounts for its induction in IEC-6 cells in culture. AB - Putrescine, the product of the ornithine decarboxylase (ODC)-catalyzed reaction, stimulates macromolecular synthesis in a duodenal crypt cell line, IEC-6 cells, grown in culture. In addition, supplementation of medium with putrescine alone reverses the inhibition of proliferation produced by inhibition of ODC with difluoromethylornithine (DFMO). A series of experiments was initiated in the IEC 6 cell line to study the regulation of induction of ODC, as this enzyme is rate limiting in putrescine synthesis. Five percent fetal bovine serum (FBS) and 10 nM IGF-II stimulated a 21-fold and 6-fold induction of ODC activity, respectively. Kinetic analysis indicated that the effect was on the Vmax of the reaction and not on the Km, suggesting an increase in total ODC protein. This was verified by measuring [3H]DFMO binding; serum-stimulated induction of activity was accompanied by a corresponding 20-fold increase in the specific binding of DFMO to ODC. In contrast, Northern analysis demonstrated only a two-fold change in ODC mRNA level during induction. Measurement of enzyme stability showed that the half life of the ODC protein was increased three-fold above basal level in the induced state. Inhibition of induction was produced by pretreatment with either the calmodulin antagonist, W-7, or the product of the ODC-catalyzed reaction, putrescine. Further analysis illustrated that the inhibition produced by these agents was partly the result of destabilization of the enzyme and not a decrease in message level. These results demonstrate that the induction of ODC by trophic agents is the result of post-transcriptional events rather than at the level of RNA synthesis. PMID- 2262071 TI - Effects of CCK on gene expression of endocrine pancreatic hormones. AB - Regulation of endocrine pancreatic hormone gene expression by cholecystokinin (CCK) was examined in the rat using cloned cDNA probes to quantify changes in specific mRNAs (insulin, glucagon, pancreatic polypeptide and somatostatin). Plasma CCK levels were raised to concentrations comparable to physiologic postprandial values either by including soybean trypsin inhibitor (SBTI) in the intraduodenal perfusate of an elemental diet (6.9 +/- 1.0 pM, n = 6), or by intravenous infusion of CCK-8 (6.0 +/- 0.9 pM, n = 6). SBTI infusion for 48 h resulted in a three- to fourfold increase in procarboxypeptidase B and kallikrein mRNA levels. Similar increases were observed when CCK was infused intravenously for 24 h. In contrast, neither SBTI intraduodenally, nor intravenous CCK had any effects on mRNA levels of insulin, glucagon, PP or somatostatin. These data therefore indicate that CCK at physiologic postprandial plasma concentrations stimulates pancreatic protease gene expression but has no effects on gene expression of endocrine pancreatic hormones. PMID- 2262072 TI - Facts and problems of the intestinal basement membrane. AB - The importance of the intestinal subepithelial basement membrane has been the topic of a new field of gastrointestinal research. Its chemical structure consisting of collagenous and noncollagenous multidomain macromolecules has become unraveled with the help of specific antibodies. Functional aspects have been tested in cell cultures and tissue recombination experiments. Here, current data are reviewed and remaining problems specified. The persistent influence of the subepithelial myofibroblast on the formation and maintenance of the subepithelial basement membrane and the reciprocal interaction between epithelial cells, their basement membrane and the myofibroblast suggest a broader definition of the intestinal epithelium to include these elements. PMID- 2262073 TI - Polyamines in human gastrointestinal malignancies. AB - This study was designed to investigate the clinical relevance of polyamine determination in human tissue, serum, and urine as diagnostic markers in the diagnosis or postoperative control of patients with gastrointestinal cancer. Total, free, and acetylated polyamines were measured simultaneously in tissue, serum, and urine of patients with esophageal (n = 16), gastric (n = 40), pancreatic (n = 20) or colorectal (n = 50) carcinoma, in 40 patients with non malignant gastrointestinal diseases, and 30 healthy volunteers. Though sensitivity of polyamines for gastrointestinal cancer proved to be high, non malignant gastrointestinal diseases partly showed similar elevated polyamine concentrations in urine and serum which resulted in a low specificity of polyamines for gastrointestinal cancer. Therefore polyamines are not suitable as diagnostic markers in tumor screening. Furthermore, since polyamine concentrations in serum and urine normalized after curative operation while they were further increased and elevated in patients with proven relapse of the tumor or metastases, polyamines might be of clinical value in postoperative monitoring of therapeutical success or predicting relapse of the tumor. PMID- 2262074 TI - Adaptation of epithelial ion transport in the short bowel syndrome. AB - Ileal remnants 8 weeks after 70% proximal small intestinal resection were used as a model for the short bowel syndrome in man. For comparing active ion transport between control ileum and short bowel with the Ussing technique, the relative contribution of the subepithelial resistance has to be considered. Epithelial/subepithelial voltage divider ratios were determined in the Ussing chamber by positioning the tip of a microelectrode just below the epithelium. In control ileum, the ratio of total to epithelial voltage deflection was 1:0.56 +/- 0.03 (n = 48) and decreased to 1:0.42 +/- 0.01 (n = 67; p less than 0.001) under the short bowel condition. Thus, the factors by which a measured short-circuit current (Isc) underestimates the true electrogenic transport was 1.78 +/- 0.09 (n = 48) in control ileum and 2.36 +/- 0.08 (n = 67; p less than 0.001) in the short bowel. Glucose-dependent electrogenic Na absorption was defined using bathing media containing 48 mM 3-o-methyl-glucose as the decrease in Isc (delta Isc) after addition of 0.5 mM phlorizin. After correction for the respective contributions of the subepithelial resistance, delta Isc was -1.4 +/- 0.2 microEq.h-1.cm-2 (n = 13) in control ileum and -3.2 +/- 0.7 microEq.h-1.cm-2 (n = 11; p less than 0.01) in the short bowel. We conclude that the mucosa in the short bowel syndrome is characterized by an increase in glucose-dependent electrogenic Na absorption, probably as an adaptive response to the reduced overall absorptive area of the remaining intestine. PMID- 2262075 TI - Pre-translational, translational, and post-translational mechanisms in adaptation of intestinal proteins. AB - The enterocyte exhibits remarkable short-term adaptation to a meal, complementing the well recognized adaptation of the stomach and pancreas. The mechanisms utilized include increased protein synthesis by pre-translational and translational events, and post-translational alterations in protein degradation and secretion. All of these events occur within a few hours after the meal. These adaptations are compared with the more long-term events in post-natal development that occur over a period of days, at least in the rat. They contrast even more with the macroscopic changes that also occur over days and weeks following intestinal resection, the model most commonly associated with the concept of intestinal adaptation. The demonstration of cellular and molecular adaptation within a few hours of a meal represents an expansion of the definition of intestinal adaptation and may provide clues to the explanation of more delayed events. PMID- 2262076 TI - The role of gut-glucagon-like immunoreactants in the control of gastrointestinal epithelial cell renewal. AB - In vitro and in vivo studies have provided considerable information on the possible physiologic function of circulating gastrointestinal hormones as well as locally acting regulatory peptides in the multifactorial control of adaptive gastrointestinal epithelial cell proliferation and cell renewal. It has been suggested by circumstantial evidences that enteroglucagon (EG; G-GLI I) may act as a trophic factor on the intestinal mucosa which may account for adaptive changes of the small intestine following various stimuli. However, we have shown that there are experimental conditions (germ-free rats after conventionalisation; jejunal self-filling blind loops) in which intestinal hyperplasia does not correspond to an increase in the concentrations of enteroglucagon in plasma or intestinal mucosa. Furthermore, despite a continuous immunoneutralisation of circulating endogenous enteroglucagon by monoclonal antibodies there was an adaptive, hyperplastic response of the ileal remnants after a 70% proximal small bowel resection which was of the same magnitude as in the control group but was even greater considering the increased number of mitoses per crypt. In order to gain additional insight into the putative role of enteroglucagon as an enterotrophic regulatory peptide, an in vitro model was used to investigate the effect of highly purified rat G-GLI I on the proliferative response of primary small intestinal epithelial cells of fetal rats. Whereas there was a well known growth-promoting action of EGF, the proliferation of rat fetal intestinal epithelial cells was inhibited by the addition of purified G-GLI I. These results indicate that enteroglucagon does not act as an enterotrophic factor but provide the first direct evidence consistent with an antitrophic role of enteroglucagon in the small intestine. PMID- 2262078 TI - Hormones and receptors in gastrointestinal malignancies. AB - Receptors for several polypeptide hormones have been demonstrated in cells of the gastrointestinal tract and pancreas. Some of these polypeptides stimulate or inhibit cell division. Therefore, these receptors have been sought in carcinomas arising from these tissues, and several examples have been reported. In some instances, stimulation of tumor growth by the corresponding ligand has been demonstrated or blocked by a receptor antagonist. In experimental carcinogenesis, the incidence of tumors has been influenced by some of the same hormones. Receptors and binding proteins for steroid hormones also have been reported in carcinomas of the pancreas. Manipulation of sex steroid hormones has yielded both inhibition and enhancement of growth of human and rat pancreatic cancers. These observations imply that trophic or growth inhibiting polypeptide and steroid hormones may serve as promoters or inhibitors of carcinogenesis in gastrointestinal organs and may influence the growth of established carcinomas. Receptor blockers may provide a clinical approach for slowing the growth of some gastrointestinal cancers. PMID- 2262077 TI - Molecular biology of gastrointestinal peptides and growth factors: relevance to intestinal adaptation. AB - New approaches towards understanding regulation of growth and adaptation of the small intestine are made possible by the isolation and characterization of genes and complementary DNAs (cDNAs) encoding gastrointestinal peptides, growth factors and their receptors. Nucleotide sequencing provides prerequisite structural information. Analyses of gene expression by quantitation and localization of mRNAs provide information about correlations between local alterations in peptide or receptor synthesis and intestinal growth. Analyses of intestinal growth in transgenic animals that overexpress or underexpress growth factor or receptor genes provides direct information about peptide effects on growth. Our recent studies with genes and cDNAs encoding proglucagon and the growth hormone dependent insulin-like growth factor 1 (IGF-I) represent examples of these approaches. Sequences of proglucagon and IGF-I cDNAs provide the primary structures of the peptide precursors. Analyses of proglucagon mRNA during adaptive growth after small bowel resection indicate that increases in proglucagon gene transcription or mRNA stability underly previously observed increases in serum enteroglucagons during adaptive growth. Analyses of IGF-I mRNAs in intestine indicate that small intestine expresses only a subset of the IGF-I mRNAs expressed in liver due to utilization of specific promotors and/or exon splicing mechanisms. Oligomers derived from the 3' end of the rat IGF-I gene detect a novel intestinal specific IGF-I related mRNA that shows an aboral decline in abundance from duodenum to colon and is upregulated in a number of situations of adaptive growth. Transgenic mice that overexpress growth hormone or IGF-I are under analysis to establish the effects of growth hormone and IGF-I on intestinal growth. PMID- 2262079 TI - Cloning of canine gastrin cDNA's encoding variant amino acid sequences. AB - We have isolated 2 clones encoding gastrin from a canine antral mucosa cDNA library. The clones differed in nucleotide sequence at 2 sites in the coding region. One of the clones confirmed the amino acid sequence of dog gastrin obtained by peptide purification and analysis. An A-G substitution in the other clone resulted in a Thr-Ala substitution in the region encoding the biologically active carboxyl-terminal portion of gastrin. The source of the observed heterogeneity in cDNA sequences is not known but its location may have implications with regard to the physiology of gastrin in dogs. PMID- 2262080 TI - The effect of reference microphone placement on sound pressure levels at an ear level hearing aid microphone. AB - The present study was designed to investigate the effects of reference microphone location on probe tube microphone measures of hearing aid response. The reference microphone of a clinical probe tube microphone system was located either at a position on the cheek (position A) or in close proximity to the microphone of an ear level hearing aid (position B). With sound pressure level (SPL) held constant at the reference microphone, the SPL at the position of the hearing aid microphone was measured at 14 test frequencies using a 1/8-inch condenser microphone. Measures were obtained on ten male and ten female subjects. Results indicated large frequency-dependent deviations in SPL at the hearing aid microphone, compared to that measured at the reference microphone, when the reference microphone was at position A. In the 1200 to 2000 Hz range, the SPL at the hearing aid microphone was as much as 9.5 dB higher than at the reference microphone. There were no large frequency-dependent variations with the reference microphone in position B, but the SPL at the hearing aid microphone location was approximately 3 dB higher than at the reference microphone. Results suggest that estimates of hearing aid output can be affected markedly by the reference microphone location. Clinical implications of the impact of reference microphone location on probe microphone measures of hearing aid gain and saturation sound pressure levels are discussed. PMID- 2262081 TI - Signal averaging in real ear probe tube measurements. AB - In this study, signal averaging measurements were performed using a broadband noise as the test signal in two acoustic environments typifying relatively noisy situations in which real ear probe tube measurements are made clinically. The minimum time-domain signal averaging required to reduce the degrading effects of background noise to levels acceptable for the production of valid real ear unaided responses (REURs) was established for three normal listeners at various signal-to-noise (S/N) ratios. Generally, averaging was not required at S/Ns of 20 dB or higher. Acceptable responses were obtained at S/Ns as low as -5 dB when the number of averages was increased to 256 and higher. The function derived from the data in the two acoustic environments was in good agreement with a theoretical rule. Findings suggest that averaging of only a few sweeps of the test signal is required to obtain reliable and valid real ear measurements, even in somewhat noisy test environments. With a knowledge of the levels of the test signal and the background noise, data from this study can be used to determine the requisite number of signal sweeps to be averaged in acquiring real ear responses in a minimum amount of time. PMID- 2262082 TI - Preliminary studies on the use of an ABR amplitude projection procedure for hearing aid selection. AB - Hearing aid selection in young nonverbal children is difficult and objective selection procedures are needed. Kiessling (Scand Audiol 1982;11:269-275; Arch Otorhinolaryngol 1983;238:233-240) has proposed an objective hearing aid selection method based on an unaided ABR amplitude projection procedure. However, Kiessling's ABR projection method is based on the assumption that ABR amplitude is directly related to the loudness of a signal--an assumption which has not been tested. This assumption was investigated in a group of ten normally hearing and three hearing-impaired listeners. The results indicated that ABR amplitude measures obtained in a single trial do not always correlate well with perceived loudness, but ABR amplitudes averaged over several trials do correlate well with estimates of perceived loudness. The hearing-impaired listeners then participated in a second phase of the investigation in which hearing aids chosen by the ABR projection procedure were compared with hearing aids chosen by more conventional methods. The results indicated that the projection procedure prescribed appropriate gain and compression characteristics for two of the three hearing impaired listeners. PMID- 2262083 TI - Feasibility of auditory event-related potential measurement in brain injury rehabilitation. AB - Measurements of auditory event-related potentials (AERPs) from brain injury rehabilitation patients may provide information on neural function related to cognitive processes important to the recovery of social and intellectual skills. The present study investigated the feasibility of measuring AERPs from 50 brain injury rehabilitation inpatients at various stages of cognitive recovery including comatose to automatic-appropriate function. Patients from levels II through VII on the Rancho Los Amigos Scale of Cognitive Function were studied. Results indicated that waveforms showing N1, P2, N2, and P3 components could be recorded from individual patients at each of the RLAS levels we studied, except level IV where only 1 patient was tested. However, considerable variability in waveforms was also observed at each scale level. No statistically significant relationships were demonstrated between AERP components and all other evoked potential, central auditory, and audiometric test results for 30 patients at RLAS level VII (automatic-appropriate). Overall results suggested a need for research focused on electrophysiologic and behavioral measures that can be used in conjunction to better describe auditory function and prognosis in brain injury patients. PMID- 2262084 TI - Spectral differences in the ABRs of old and young subjects. AB - The purpose of the present study was to analyze and compare the amplitude spectra of ABRs recorded from 40 elderly and 40 young subjects in order to determine if there are any age related differences. A spectral analysis was performed on each subject's ABR. It was found that the ABRs recorded from older subjects have a significantly greater amount of low frequency spectral energy than ABRs recorded from young subjects. This difference was attributed to the greater amount of low frequency background noise found in the ABRs of older subjects. Modification of standard recording procedures should be considered when ABRs are recorded from older subjects. PMID- 2262085 TI - Asymmetric brain stem auditory evoked responses in infants treated with extracorporeal membrane oxygenation. AB - Brain stem auditory evoked responses (BAERs) were obtained in 25 infants who received extracorporeal membrane oxygenation (ECMO) for severe respiratory failure. Tracings were obtained by means of a Nicolet CA-2000 averager, using a conventional paradigm. The presence or absence of replicated responses at 35 and 75 dB nHL were recorded for each ear. Interpeak latencies I-III, III-V, and I-V were measured and differences between right and left ears were compared, using a matched pair t-test. Wave III-V latencies were longer on the left than right (p less than 0.05), but no significant right-left differences for latencies I-III were noted. Sixteen percent of the infants failed hearing sensitivity criteria, 45% (10/23) had prolonged I-V latencies. At follow-up (age 4 to 12 months) 6/10 infants with prolonged I-V latencies had additional neurologic abnormalities. In this population left ear III-V latencies are prolonged versus right, and the incidence of abnormal BAERs is high. Relative prolongation of left ear III-V latencies (generated from the right brain stem) may be result of right carotid artery and/or jugular vein ligation for ECMO, and abnormal I-V latencies prognosticate future neurologic abnormalities in this population. PMID- 2262086 TI - Effect of temporal area bone vibrator placement on auditory brain stem response in newborn infants. AB - The effect of bone conduction vibratory placement on the temporal area, revealed by the auditory brain stem response (ABR), in newborn infants, was investigated. Twenty-five full term neonates were tested at 48 to 72 hours postparturition. ABR wave V latencies were obtained from three different temporal area postauricular vibrator placements at 15 and 30 dB nHL stimulus intensity levels. Results showed that significant ABR wave V latency shifts were observed with changes in the three vibrator placements (p less than 0.05). It is suggested that, with ABR testing in newborn infants using bone conducted stimuli, bone vibrator placement on the temporal area remain consistent. PMID- 2262087 TI - Electrically elicited stapedius reflex in cochlear implant patients. AB - Electrically elicited stapedius reflexes were examined in 25 deaf patients who had received a 22-channel Clark/NUCLEUS cochlear implant. Using an apical, a medial and a basal electrode pair, different stimulation positions within the cochlea and different stimulation modes were examined. For threshold determination, 10 reflexes were averaged with reflexes recorded on the nonoperated side. Reflexes were elicited in 19 of the 25 patients (76%); a saturation of reflex amplitude could be recorded in 14 (56%) subjects. In two additional cases, a reflex could be obtained by increasing the bipolar stimulation width (changing the stimulation mode). In comparison with different stimulation positions within the cochlea, the stimulation of apical electrodes produced more distinctive reflexes and required lower current levels. An increase in the bipolar stimulation width also decreased the intensity required for stapedius reflex threshold. Our data suggest that stapedius reflex evaluation may be a useful tool for speech processor fitting. PMID- 2262088 TI - Parents' evaluations of the effects of the 3M/House cochlear implant on children. AB - A questionnaire was used to obtain parents' opinions of their children's 3M/House cochlear implant. Responses were received from parents of 132 children aged 3 through 17. Seventy-five percent of the parents were satisfied overall with the implant; 25% were not. The parents were more positive about the implant than they felt their children were. Fifty-seven percent, 34%, and 9% of the parents reported that the implant performed better, the same, or worse, respectively, than their implant counselors said it would. Almost all of the parents (98%) said they would recommend the implant to other parents. The parents thought that the effect of the implant on environmental sound perception and speech production was superior to its effect on speech perception. Environmental sound perception was a more substantial predictor of parental satisfaction than was speech perception or speech production. About half of the parents felt that the size and cords of the external processor were problematic. Adolescent children wore their implants less than preadolescent children. It was concluded that the majority of the parents thought the 3M/House cochlear implant provided real-world benefits for their children. PMID- 2262089 TI - The effects of hypoxic hypoxia on brain stem mediated stapedial reflex in healthy volunteers. AB - The stapedial reflex is routinely used both in hearing evaluation and to distinguish cochlear from retrocochlear lesions. The present study was carried out on seven healthy volunteers in the hope of obtaining basic information about the physiological variables of stapedial reflex using hypoxic hypoxia. The results show that a short-term hypoxic hypoxia affects, for the most part, the muscle contraction velocity and the amplitude of the reflex, whereas the latency remains unchanged. This finding indicates that the arterial O2-saturation may have an influence when studying the effects of breathing depressive drugs or in patients with decreased ventilation capacity. PMID- 2262090 TI - Noise levels in physicians' offices. AB - The development of hand-held auditory screening devices has led to increased hearing screening by physicians. Ambient noise levels were assessed in examination rooms of 20 physician offices. Measurements provided Ln, Leq, Lmax, and octave band data for specialty types: pediatrics, internal medicine, family practice and otolaryngology. Such data should not replace the need for individually monitoring potential screening sites. PMID- 2262091 TI - National AIDS information system. Toronto. PMID- 2262092 TI - Materials management: a significant source of revenue. PMID- 2262093 TI - Electronic data interchange finds a ready home. PMID- 2262094 TI - Computerization of a multi-inventory system. PMID- 2262095 TI - Environmentally friendly waste management. PMID- 2262096 TI - A joint venture of a different kind. PMID- 2262097 TI - Health technology assessment in Canada. PMID- 2262098 TI - The logistics principle. PMID- 2262099 TI - Pharmaceutical company-sponsored promotions. PMID- 2262100 TI - STFM--the future? AB - This article is intended to inform STFM and NAPCRG members of current developments regarding this organizational process and the future of each organization. These preliminary discussions have provided a basis for determining how family medicine can be more effective as an academic discipline. The board of directors and the officers of STFM are supportive of this concept. This process will ultimately enable the members of STFM and our colleagues in academic family medicine to better fulfill the goals and mission of academic family medicine in the future. PMID- 2262101 TI - Geriatric fellowships. PMID- 2262102 TI - Time for change. PMID- 2262103 TI - A comparison of resident perceptions of training experience at university and community based family practice residencies. AB - To determine if differences exist in the perception by residents of the adequacy of training at university or community based programs, a survey was conducted of all 1987 family practice residency graduates in the United States. Of the 2,363 questionnaires mailed and reviewed by graduates, 1,583 were returned (66.8% response rate). Respondents completed the survey within approximately 18 months of completing residency training. The results indicate that overall satisfaction with training, as well as the perception of adequacy of preparation for practice, lessened with increasing university affiliation of the training program (P less than .05). The findings reported here also suggest that university based family practice residency graduates are much more likely to report being treated like "second-class citizens" by attendings and residents of other specialties. In addition, satisfaction with educational rotation experiences is less if competing residencies exist at the institution sponsoring the residency. PMID- 2262104 TI - The psychosocial M & M: a tool in reinterpreting problematic medical situations. AB - This article explores the concept of a psychosocial morbidity and mortality (M & M) conference as a useful adjunct to the traditional M & M in physician education. It argues that understanding significantly unexpected and disturbing patient outcomes often requires a shift in the analytic paradigm used and offers an interpretive and relational perspective as a way to deepen the understanding of physicians-in-training. In particular, it is argued that the psychosocial M & M can highlight previously missed or trivialized dimensions of patient, family, and physician interactions which affect care and, simultaneously, can help address the affective distress of the physician-in-training which results from a difficult and painful case. Definition, goals, and a theoretical formulation are provided, as well as a detailed description of how a psychosocial M & M might be conducted. A discussion of potential difficulties and anecdotal positive outcomes are also included. PMID- 2262105 TI - Factors associated with the frequency of after-hours in-person patient consultations. AB - In this study, 901 after-hours calls to 26 second- and third-year family practice residents in a university based program were audited to determine patient and physician characteristics associated with after-hours rates of in-person consultation. In-person consultation frequency averaged 25.5%, but ranged from 9% to 53% among physicians (P = .02). Male patients were seen more frequently than female patients (P = .008) Younger patients were seen more frequently than older patients (P = .01). Calls for trauma, obstetrics, and respiratory complaints were more likely to result in in-person consultations than were calls for other problems (P less than .00001). Categorical modeling analysis, used for adjustment, confirmed differences in consultation frequencies both among physicians and due to the nature of the caller's complaint. Neither the time of the call, the patient's race, nor the physician's sex, marital status, level of training, distance lived from the family practice center, or personality type as measured by the Myers-Briggs Type Indicator were associated with the frequency of consultation. Additional research is needed to determine the factors responsible for physician differences in after-hours in-person consultation frequency. PMID- 2262106 TI - Patient perceptions of humanism in physicians: effects on positive health behaviors. AB - Although humanism has emerged as an important issue in medical education and practice, there is no standardized definition of humanism or an instrument that measures patients' perceptions of their physician's level of humanism. This study addressed these three issues: 1) A definition of physician humanism was developed based on the current literature; 2) an instrument was designed that measured patients' perceptions of humanism in their family physicians; and 3) health outcome variables were measured relative to these perceptions. The design was a cross-sectional survey of 185 randomly selected patients from two family practice sites. The questionnaire consisted of a humanism scale, in addition to items to assess patient satisfaction and patients' adherence to medical advice regarding exercise, diet, and smoking cessation. A positive association was found between perceived physician humanism and patient satisfaction. Greater success in patients' attempts to quit smoking was associated with higher physician humanism. The implications of these findings for evaluation and training of health care providers and patients' use of health care services are discussed. PMID- 2262107 TI - Physician-patient familiarity and patient recall of medication changes. The Collaborative Study Group of the SGIM Task Force on the Doctor and Patient. AB - Although patients regularly see the same physicain for medical care, little is known about the effects of physician-patient familiarity on important visit outcomes. In a study of visits made to 79 physicians in 11 primary care settings, investigators sought to determine: 1) whether patient recall of prescription medication changes improved as physician-patient familiarity increased, and 2) whether characteristics which predicted recall for newer patients also predicted recall for intermediate and established patients. Sixty-six percent of patients recalled all medication changes recommended during the visit. While recall did not improve as physician-patient familiarity increased, predictors of recall did differ. Generally, the more drug information the physician gave during the concluding segment of the visit, the fewer drug changes the patient remembered. However, this relationship reversed as physician-patient familiarity increased. Elderly patients demonstrated diminished recall regardless of the number of previous visits. The findings suggest that the lengthy provision of drug information actually succeeds in heightening medication recall only when the physician and patient have a well-established relationship. In earlier stages, asking patients to restate recommendations may be a more effective strategy to enhance patient recall. PMID- 2262108 TI - A pilot study of the prevalence of herpes genitalis among selected groups of patients seeking care in a family practice center. AB - Herpes genitalis is typically studied in patient panels identified at specialized sexually transmitted disease clinics or with information obtained from herpes self-help groups. This article reports the results of a descriptive pilot study of the prevalence of herpes genitalis in family practice. The feasibility of obtaining psychosexual information on sexually transmitted diseases from more than 600 patients from five family practice practices was assessed. These initial data show that in the family practices participating in this study: 1) genital herpes is a low prevalence disease; 2) psychosocial adjustment to the disease among infected persons is usually reported as good, apart from sexual effects; and 3) close to 30% of the study population reported having prior sexually transmitted diseases. Problems involved in generalizing the results of this research and the limitations of conducting collaborative clinical research in family practice settings are reviewed. PMID- 2262109 TI - Factors associated with persons with panic attacks seeking medical care. AB - There is increasing evidence that panic disorder is a major health problem in the United States. Yet, it is believed that many panic disorder patients do not enter the health care system, and those who do rarely offer a mental health complaint. This study was conducted to determine factors important in the decision of patients with panic disorder to seek health care, where they go for care, and their complaints to physicians. Overall, 44% of patients did not enter the health care system with complaints of either nervousness or panic attacks. Certain factors were found to be important to the patient's decision to seek care and where to go for care, including being white, having panic-related symptoms, educational level, and feeling free to discuss panic. Gender, marital status, age, phobic avoidance, limited-symptom attacks, and fear during panic were not important factors in the decision to seek health care. Through a better understanding of the important factors, health care givers can be more sensitive to the diagnosis of panic disorder in patients who do seek care and look for ways of reaching those who do not. PMID- 2262110 TI - A residency curriculum for the future. The STFM Task Force on Residency Curriculum for the Future. AB - A new family practice residency curriculum in the format of the special requirements for residency training is proposed. This new curriculum consolidates the original principles of family practice with current developments in medical practice and changes in society. The emphasis is on increased flexibility, a competency-based curriculum, an extensive evaluation and audit system, curricular control by family practice faculty, increased ambulatory care training, a commitment to the biopsychosocial model and community-oriented primary care, and the reiteration of the basic core of medical knowledge and clinical skills. PMID- 2262111 TI - Relationships with AIDS patients: clinical metaphors and preventive bioethics. AB - AIDS, more than most diseases, evokes compelling and tragic stories. The AIDS epidemic is "The Plague." We seek the optimally therapeutic relationship, embodied in the metaphor of the covenant. There is a fundamental human possibility of healing through dying. "Death teaches us to live." We advocate asking AIDS patients the explicit question, "How do you want me to work with you?" This can generate conversations that facilitate congruence in relationships. A reluctance to talk about uncertainties and limits is a major source of preventable ethical conflict and a major obstacle to fulfillment of the therapeutic possibilities of the doctor-patient relationship. The Durable Power of Attorney for Health Care (DPA) can be helpful in facilitating discussions with patients and their families. Successful "preventive bioethics" is communication that opens for the patient and doctor the broadest possibilities of hearing, understanding, and expressing. The doctor as parent, fighter, technician, teacher, and covenanter may be important roles at appropriate moments with a given patient who may be experiencing the disease variably as infectious chaos, brutal enemy, spiritual challenge, or opportunity for growth. The context of such communication is a real relationship that includes love, respect, humor, hope, and genuine interest in how this other person lives. PMID- 2262112 TI - Designing self-report instruments for family assessment. AB - As family medicine research expands, more and better self-report measures for quantifying family systems variables will be required. These measures should be developed from an accepted paradigm for instrument design that includes the following. They should be: 1) grounded in a contemporary conceptual framework; 2) constructed following a rational theoretical design that includes the sequential stages of construct identification, construct definition, item generation, item editing, item formatting, and item scoring; 3) analyzed empirically at the item level for item distribution characteristics, item-scale correlation, and item response style correlations; 4) analyzed at the scale level for scale distribution characteristics, scale-scale correlations, and scale-response style correlation; 5) revised based on editing and empirical analysis; and 6) psychometrically evaluated for reliability (eg, internal consistency, test retest) and validity (construct related, criterion related, and content related). Normative data from various reference populations must also be obtained to provide a basis for interpreting scores. Finally, test manuals must be written to summarize test development data and provide information on administration procedures, scoring, and interpretation. PMID- 2262113 TI - Consultations from a family medicine inpatient service. AB - The pattern and rate of consultation from a family practice residency program inpatient service were examined. The most frequently consulted medical specialty was cardiology; the most frequently consulted surgical specialty was general surgery. The overall consultation rate was 50%. The consultation rates for the most frequent discharge diagnoses were examined. Pediatric admissions were less likely to received consultations than adult or geriatric admissions. The results of this study suggest that family physicians are able to manage most of their hospitalized patients without consultation. PMID- 2262114 TI - The effect of faculty private practice experience on appropriate charging for professional services. AB - Private practice experience is widely considered invaluable for academic family physicians, especially for clinical efficiency and for charging appropriately for professional services. This study tested the hypothesis that faculty members with private practice experience charged more appropriately for professional services. Patient-physician encounters were rated in terms of propriety of charges by consensus of two faculty physicians and compared to the actual level of service marked on the encounter form. Private practice experience for faculty resulted in less undercharging (21% of encounters undercharged versus 31% for faculty without that experience, P = .03). Physicians with private practice experience undercharged on average $.36 per encounter, versus $1.94 for providers without that experience (Kruskal-Wallis test, P = .27). Physicians with private practice experience also tended to perform more procedures but not to bill for more. Academic family physicians with private practice experience demonstrated more appropriate billing practices for professional services, but ideally preference for this type of academic physician should be based on other attributes, such as breadth of experience and efficiency in patient care. PMID- 2262115 TI - [Dietary factors in the pathogenesis of alcoholic cirrhosis: what's new?]. PMID- 2262116 TI - [Calibrated side-to-side portacaval anastomosis in the treatment of bleeding from ruptured esophageal varices. Results in 38 cirrhotic patients]. AB - We report the clinical results of 38 calibrated side-to-side portocaval shunts performed in patients with hemorrhagic liver cirrhosis (alcoholic in 90 percent of cases). The operative mortality (at 2 months) was 10.5 percent. The rate of recurrent bleeding was 2.6 percent; hepatic encephalopathy was encountered in 16 percent (acute encephalopathy: 6.5 percent; chronic encephalopathy: 9.6 percent; this rate decreased to 3.2 percent after anastomotic narrowing). Hepatopedal portal blood flow was maintained in 74.3 percent of cases in the early postoperative period (83.3 percent since the portacaval pressure gradient was maintained at 2/3 of the initial gradient) and disappeared with time in 75 percent of cases. The survival rates at 1 and 4 years were 79.4 percent and 60 percent, respectively, for all patients (94.4 and 83.3 percent for Child A patients) with a normal social activity in 90 percent of cases. Twelve patients developed hepatocellular carcinoma. These clinical results are similar to those observed after selective shunts and suggest that the side-to-side calibrated portacaval shunt is an excellent procedure for the treatment of bleeding esophageal varices in case of failure or contraindication to endoscopic sclerotherapy or in patients with chronic ascites and good liver function. PMID- 2262117 TI - [Characterisation of 2 reversible states of the inositol 1,4,5-trisphosphate receptor in rat hepatocytes]. AB - Myo-inositol-1,4,5-trisphosphate or (I(1,4,5)P3) is generated in liver cells after hormonal stimulation. It bind to specific receptors and induces the release of Ca2+ from an intracellular store. This receptor has been found in permeabilized hepatocytes and showed two states of low- and high-affinity with KD of 1-2 and 40-50 nmol/l, respectively. Measurements of 45Ca2+ release, mediated by different analogues, revealed that the low-affinity site was coupled to the Ca2+ channel open state. The pretreatment of cells with vasopressin, an I(1,4,5)P3-dependent agonist, induced an 60 percent increase of the binding capacity of the high-affinity sites. Incubation with 1 mumol/l Ca2+ increased the number of high-affinity sites from 5 to 65 fmol/10(6) cells. This effect was associated with a decrease in the number of low-affinity sites from 130 to 80 fmol/10(6) cells. Our results suggest that the intracellular Ca2+ concentration rise mediated by I(1,4,5)P3-dependent agonists, induced a conversion of the low affinity form of the I(1,4,5)P3 receptor, coupled to Ca2+ release, to a desensitized high-affinity one. This process could explain the oscillations of the intracellular Ca2+ concentration observed in hormone-treated single cells. PMID- 2262118 TI - [Is peptic ulcer a seasonal disease?]. PMID- 2262119 TI - [Intermittent treatment or preventive treatment of recurrence in duodenal ulcer disease? A controlled, double-blind study with 150 mg ranitidine daily for one year]. AB - This 1-year study compared two pragmatic strategies in long-term management of duodenal ulcer: continuous treatment with ranitidine 150 mg after dinner and treatment of duodenal ulcer attacks with ranitidine 300 mg and placebo in the interval. A multicentric, randomized double-blind study was conducted in 399 patients, 197 in the ranitidine group and 202 in the placebo group. Efficacy was judged by the prevalence of ulcer-pain recurrences; secondary criteria were the prevalence of endoscopic recurrences, complications and the number of facultative visits, hospitalizations and days off work related to duodenal ulcer disease. Both groups were similar with regard to main epidemiologic features and number of drop-outs (10.5 percent). Fifty-two patients were withdrawn for symptomatic or endoscopic relapses: 6 in the ranitidine group, 46 in the placebo group (p less than 0.05). Sixty-six percent of the patients remained asymptomatic at one year in the ranitidine group versus 33 percent in the placebo group (p less than 0.001). Seventeen patients with ranitidine (8.6 percent) and 59 with placebo (29.2 percent) experienced at least one endoscopic recurrence (p less than 0.05). In the placebo group, 8 complications were observed (bleeding = 5, duodenal stenosis = 3), and none in the ranitidine group (p less than 0.005). Patients with ranitidine had significantly less facultative visits and endoscopies, number of days off work, and hospitalizations (p less than 0.05). Tolerance was good (5 percent side-effects, all minor) and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262120 TI - ["Ambulatory" ischemic colitis. Clinical course and etiologic features in 88 cases]. AB - From January 1983 to December 1988, 88 consecutive patients with ambulatory ischemic colitis without severe disease or surgical operation were observed. The diagnosis was established in all cases by endoscopy, and in 64 cases by histologic examination. The study included 55 women and 33 men with a mean age of 65.4 years (22-90). Symptoms included: abdominal pain (73 percent), diarrhea (60 percent) and bloody stools (85 percent). The sequence abdominal pain-diarrhea bloody stools was noted in 41 percent of cases. Most cases of colitis were located in the sigmoid and left colon. The immediate course was uneventful in 81 patients. Six patients underwent surgery and of these, three died. The mortality rate was 4.5 percent (4 cases). Long-term outcome was known in 41 cases. None of the patients were symptomatic, but a moderate secondary stenosis was noted in 4 of 31 patients who underwent endoscopic or radiological follow-up examination. In 80 cases, one or more potentially etiological factors were observed including vascular obstruction (32 cases), low-flow states (27 cases), and drugs (78 cases). Twenty patients were taking non steroidal anti-inflammatory drugs (23 percent). Drug treatment was recent in 10 cases, and in four, it was the only possible etiological factor. This suggests the responsibility of anti inflammatory drugs in the onset of certain cases of ischemic colitis. PMID- 2262121 TI - [Evaluation of an automated pH-monitor and its logic of calculation]. AB - The aim of this study was to compare the results of 3-hour postprandial esophageal pH recordings obtained simultaneously from a standard Beckmann pH recorder and a commercially available fully automated pH recording device, "pH 60" in 30 subjects. Both apparatuses were connected to the same pH probe and to a unique chart recorder to obtain simultaneous pH graphic tracings. The percentage of time between each pH level below pH 5, the percentage of time with pH less than 4 and Kaye's score were determined hourly and for the overall recording time. The pH graphic traces in both apparatuses were strictly identical demonstrating the accuracy of the analog-to-digital converter and the memory module to record pH changes. Moreover, we found a significant correlation (p less than 0.01) and a good overall agreement for all compared parameters between manual and computerized analysis. This study documents that the commercially available ambulatory esophageal pH instrument studied produces accurate data for the diagnosis of gastroesophageal reflux. PMID- 2262122 TI - [Relative importance of cholecystokinin and cholinergic nerve mechanisms in the regulation of pancreatic secretion in rats]. AB - Several substances modulate the function of pancreatic acinar cells in vitro through specific receptors. All of them may also act in vivo, but the relative importance of their effect under physiological conditions is highly variable. The aim of this study was to assess the respective participation of cholinergic nerves and cholecystokinin (CCK) in the interdigestive pancreatic exocrine secretion and in the pancreatic response to intragastric or intraduodenal nutrients. Unanesthetized rats, equipped with a semichronic (5 days) pancreatic fistula, were used. They received a test-meal in the stomach (42 kJ) or the duodenum (21 kJ), and were infused intravenously with an antagonist of muscarinic (atropine, pirenzepin), nicotinic (hexamethonium), or CCK (L364718, lorglumide, Boc-Tyr(SO3)-Nle-Gly-D-Trp-Nle-Asp-NH-CH2-CH2-C6H5) receptors. Basal interdigestive pancreatic exocrine secretion decreased significantly after atropine, pirenzepine or hexamethonium. Protein output decreased more (peak inhibition 60 to 80 percent according to the drugs, p less than 0.01 to p less than 0.001) than volume or bicarbonate output (peak inhibition 25 to 65 percent according to the drugs, p less than 0.05 to p less than 0.01). CCK antagonists did not change the interdigestive pancreatic secretion. The cumulated response to the intraduodenal meal did not change after hexamethonium or pirenzepin, but increased after atropine (by approximately 50 percent, p less than 0.001 for volume and bicarbonate output, and nearly 100 percent, p less than 0.05 for protein output). The CCK antagonists entirely suppressed the protein response to the intraduodenal meal, decreased the volume response by 70 percent (p less than 0.01), and the bicarbonate response by 50 percent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262123 TI - [Psychological stress and gastroduodenal ulcer]. PMID- 2262124 TI - [Cholecystocolic fistula: from symptoms to diagnosis]. AB - We report 2 patients with a cholecystocolic fistula in whom diametrically opposite symptoms (isolated steator-rhea, jaundice and fever) were responsible for important clinical difficulties. These fistulae are far less common than cholecysto-duodenal fistulae. Endoscopic retrograde cholangiography was performed because of abnormal liver tests and led to diagnosis in both cases. Classical aerobilia was absent in both of our cases. Barium enema was disappointing (case n. 1), whereas technetium 99m scintiscan visualized the fistula (case n. 2). Two therapeutic approaches are possible in the case of cholecystocolic fistula. Surgery, usually combining cholecystectomy and extraction of common bile duct stones with the treatment of the fistula, may be performed systematically or in case of failure of sphincterotomy (case n. 1). On the other hand, endoscopical sphincteromy during endoscopic retrograde cholangiography, which, by reducing increased biliary pressure, may be sufficient to achieve spontaneous closure of the fistula in an elderly or high risk patient (case n. 2). PMID- 2262125 TI - [Exudative enteropathy and interstitial cystitis due to systemic lupus erythematosus]. AB - A 33-year-old woman presented with chronic diarrhea, vomiting and anasarca due to systemic lupus erythematosus with protein-losing enteropathy, interstitial cystitis and glomerulonephritis. Methylprednisolone could not prevent aggravation of diarrhea, obstructive uropathy, and nephrotic syndrome, and prolonged intestinal ileus developed. Because of this steroid-resistance, bolus injections of cyclophosphamide (1 g i.v. monthly) were decided. Protein-losing enteropathy and ileus both disappeared rapidly following the first injection. Protein-losing enteropathy, intestinal ileus and interstitial cystitis are exceptional manifestations of systemic lupus erythematosus; steroid-resistance of the digestive manifestations has only been reported in one case and our observation is the first reporting the efficacy of cyclophosphamide. PMID- 2262126 TI - [Perforated tubular duplication of the sigmoid colon in adults]. AB - Intestinal duplications are rare malformations and a diagnostic challenge. The case presented herein relates to a perforated tubular duplication of the sigmoid colon in a 23-year-old man with intermittent abdominal pain during 3 months and a bout of peritonitis which resolved spontaneously. This case is unusual since duplications generally spare adults, are seldom found in the colon, and do not perforate. The only cases of duplication which can be suspected preoperatively belong to the communicating type or those containing ectopic gastric mucosa. The intraoperative finding in this case of a malformative mesenteric cyst reminds us that duplications can be found in association with other intestinal, vertebral, or genitourinary tract malformations. In conclusion, intestinal duplications should be resected even when they are asymptomatic, as occasional cancerous transformation associated with a poor prognosis have been reported. PMID- 2262127 TI - [Gastric plasmacytoma: is it a lymphoma?]. PMID- 2262128 TI - [Is fluindione hepatotoxic?]. PMID- 2262129 TI - [Hepatitis caused by benzarone: a second case]. PMID- 2262130 TI - [Protein deficiency associated with portal vein thrombosis]. PMID- 2262131 TI - [Abscess of the spleen. Successful echo-guided percutaneous drainage with double lumen catheter irrigation]. PMID- 2262132 TI - [Gastric hemorrhage and thrombosis of the splenic artery]. PMID- 2262133 TI - [Colonic preparation: once or twice?]. PMID- 2262134 TI - [Colonoscopy preparation with polyethylene glycol: several fractioned portions are preferable to single doses]. PMID- 2262135 TI - [Are tobacco and alcohol risk factors of adenocarcinoma in Barrett's esophagus?]. PMID- 2262136 TI - Genome elimination in diploid and triploid Rana esculenta males: cytological evidence from DNA flow cytometry. AB - Cytological aspects of hemiclonal (meroclonal) inheritance in diploid and triploid males of the hybridogenetic frog Rana esculenta (Rana ridibunda x Rana lessonae) have been studied by DNA flow cytometry. The fact that the R. ridibunda genome contains 16% more DNA than the R. lessonae genome provides the ability to discern cells containing genomes of any species from the water-frog complex under study. Data are presented showing that elimination of the R. ridibunda genome occurs in hybridogenetic males from certain populations. In triploid males, the cytogenetic mechanism of hemiclonal inheritance is simpler than in diploids: after the elimination of a genome (always the genome in the minority in the triploid set; "homogenizing elimination"), no compensatory duplication of the remaining genetic material is necessary, as it is in diploids. The process of elimination can be visualized in triploid males by using DNA flow cytometry to identify cells in the special phase of the spermatogonial cell cycle that we termed the E phase. PMID- 2262137 TI - New Secale cereale (rye) DNA derivatives for the detection of rye chromosome segments in wheat. AB - Subcloning of a clone of the 120-bp family of rye, pSc119, has produced two extremely useful probes. pSc119.1 assays rye-specific dispersed repetitive sequence families. It is present on all seven rye chromosomes and hybridizes to the entire length of each chromosome, with the exception of some telomeres and the nucleolar organiser region. pSc119.2, in contrast, hybridizes predominantly to the telomeric regions of rye chromosomes, with some interstitial sites. Unlike pSc119.1, it assays similar repetitive sequence families in both wheat and rye chromosomes. PMID- 2262138 TI - The macrosatellites of the Toulouse goose: the major tandemly repetitive DNA in the toulouse goose genome. AB - This paper examines the principal classes of repetitive DNA of the Toulouse goose (Anser anser) genome. There are four major classes and they are tandem repeats of less than 200 base pairs (bp). The longest repeat (class A) is 190 bp long and starts with a HinfI site. Class B is 43 bp long, commencing with a FokI site. Classes A and B show no extensive homology to DNA sequences held on a current data base (Genbank) but were confirmed to exist as major repeats in another strain of goose, the Emden goose (Anser anser) genome. Classes C and D are 5-bp repeats of 5' GAGAG 3' and 5' GGGAA 3', respectively. The macrosatellites C and D were compared with a current data base (Genbank) and were found to exist in a variety of other organisms as satellites. PMID- 2262139 TI - Two autosomal trisomies in the horse: 64,XX,-26,+t(26q26q) and 65,XX,+30. AB - The phenotypic effects in a yearling Arab filly of a newly described equine autosomal trisomy syndrome for chromosome 30 (65,XX,+30) consisted of small size and severe angular deviation of front legs accompanied by mild polydactyly, but no mental dullness. This case was associated with advanced maternal age. Additional banding studies of a second trisomy case confirmed the assignment to chromosome 26 (64,XX,-26,+t(26q26q)) and evidence of her fertility was presented. PMID- 2262140 TI - Isochromosome Y in an infertile heifer. AB - The chromosome makeup of a 3-year-old crossbred heifer was examined in an attempt to explore the cytogenetic causes of her infertility. The heifer proved to be a mosaic carrying predominantly XY cells and with approximately 30% of cells lacking a normal Y. The minor population included cells carrying a dicentric isochromosome Y and a small proportion of XO cells. Histological features of the gonads and reproductive system suggest that the presence of cells resulting from isochromosome formation and the consequent loss of the Y chromosome segment required for testicular induction may have been causally related to the embryonic state of the gonads and malformation of the duct system noted in this heifer. PMID- 2262141 TI - Use of interplasmid recombination to generate stable selectable markers for yeast transformation: application to studies of actin gene control. AB - A plasmid recombination system has been developed that relies upon interplasmid exchanges for yeast cell viability. Two types of plasmids, one carrying the LEU2 allele inserted within yeast actin gene sequences and the other carrying 2 microns plasmid DNA and an intact actin gene, were constructed. Neither plasmid alone yielded transformants in the haploid Leu- strain AH22, but when cotransformed, a number of colonies were obtained. Southern blot analysis revealed that transformants arose because of recombination events within the homologous actin sequences that transferred the LEU2 gene to the actin gene on the 2-microns plasmid. The recombinant plasmids could be recovered, and sequence analysis of one recombination site revealed that the exchange event was faithful at the nucleotide level. The resulting recombinant plasmids carried a defective actin gene and presumably arose because of a double-crossover event. Deletion mutations that prevented actin gene expression on one donor plasmid enabled the recovery at a high frequency of transformants resulting primarily from single crossover events between the two plasmids. This was presumably because such events no longer generated an intact actin gene on a multicopy plasmid. Infrequently a transformant from a plasmid with an intact gene was recovered, but in these cases the plasmid was not present in multiple copies. These cells exhibited a slower growth rate, and Northern blot analysis revealed an elevated level of actin mRNA. PMID- 2262142 TI - Comparison of the polytene chromosomes of the salivary gland, the fat body and the midgut nuclei of Drosophila auraria. AB - Photo-maps of the fat body and midgut polytene chromosomes of Drosophila auraria were constructed. These photo-maps are compared with a new, more detailed photo map of the salivary gland chromosomes of the same species. Seven, not previously described inverted tandem-duplications were detected, raising the number of such structures found in this species to 31. The constancy of the banding pattern based on the analysis of the above chromosomes is discussed. PMID- 2262143 TI - [Prognostication on the development of vibration disease in laborers using manual machines]. AB - Prognosing of vibration disease (VD) is normally made both with regard to the number of the VD cases depending on the duration of work in vibration-hazardous professions, and with respect to its latent period. The results of prognosing depend to a vast extent on the methodological principles and criteria used. The data obtained from an epidemiological survey helped to determine quantitatively the interdependence between the vibration dosage and the VD latent period calculation on the average working day dosage basis. It was also shown that in case with marked high frequency and low frequency vibrations, as well as in combinations of vibration with other industrial factors, the calculated VD period can be shortened or prolonged) by 1-3 years. Further improvement of the VD prognosing techniques should be based on the evaluation of group and individual risk-factors criteria. PMID- 2262144 TI - [Clinico-echocardiographic studies of the state of the heart in vibration disease]. AB - Established was the rate of interventricular septum asymmetrical hypertrophy and left auricle exstasia in vibration disease patients as a result of local vibration. The left ventricle myocardium contraction in major parameters (ventricular ejection, maximum ejection, ejection time and volume, the myocardium circular contraction rate and anterior-posterior contraction, systolic ejection rate) were not affected to a significant degree. The left ventricular systolic function was tending to decrease in vibration disease cases combined with IHD and AH. Desirability of using EchoCG in combination with load testing was proposed for the differential diagnosis of metabolic coronary lesions of the myocardium in vibration disease patients. PMID- 2262145 TI - [Effects of vibration and noise on the reproductive function in experimental animals]. AB - Experimental animal studies of the reproduction function were performed under prolonged vibration and noise conditions. For 4 months and 5 days male white rats were exposed to 4-hour noise and vibration effect in a noise-protected chamber. The correlated vibration velocity index was 5.07.10(-2) m/s. The permanent wide range noise level reached 92 dBA. It was established that: in a long-term experiment, vibration and noise affected the reproduction function in male white rats; in a combined vibration and noise action, marked changes in the reproduction function were revealed, and in the noise exposition alone, the function changes were not so vivid. PMID- 2262146 TI - [Evaluation of the methods of determining heat preservation of clothing protecting from cold]. PMID- 2262147 TI - [Neuro-emotional stress of work at a factory]. PMID- 2262148 TI - [State of the myocardium under the effect of high temperature of the environment (a clinico-experimental study)]. AB - The labour conditions in heat treatment shops caused the sympathetic-adrenal system's tension which was preserved in the rehabilitation period and led to ECG functional shifts. The probable traces of IHD and myocardium hypoxia were 2.7 times as often as in the workers engaged in general shops. The cardiomyocytes' damages were proved by higher levels of creatine phosphokinase and lactate dehydrogenase in the blood of heat treatment shop workers. PMID- 2262149 TI - [Work conditions and health status of specialist meteorologists working with weather charts]. AB - The contributors present a generalized description of the labour conditions' hygienic assessment and state of health of the communication service technicians and weather forecasters engaged in the State meteorology service centres in the northern and southern regions of the country. The unfavourable labour conditions' impact on the health state is revealed depending on the specificity of the weather-chart makers' working conditions, which lead to morbidity with temporary disability and occupational skin and upper respiratory tract diseases. A complex of tested measures is proposed for the improvement of the working conditions in question. PMID- 2262150 TI - [Dust factor, its effect on the body and prevention of morbidity of workers during copper and nickel ore smelting]. AB - Basing on the results of complex studies, the author provides a comparative hygienic assessment of different copper and nickel ore melting processes, which revealed a considerable contamination of the working zone air with copper and nickel containing aerosols. The workers engaged therein displayed bronchopulmonary, stomach and hepatobiliary disorders. The hygienic advantages of the autogenous ore and concentrates melting technique are proposed, along with a complex of health improving measures with a particular emphasis on the expedience of the new technological processes. PMID- 2262151 TI - [Effects of welding dust on morphology of the bronchopulmonary system and heart in experimental animals]. AB - A comparative study was made of the action of 5 intratracheally introduced dusts (of manganese, silicon, potassium, natrium, calcium, fluorine, and iron) on the cardio-respiratory system. A more marked biologic activity of the hard component of welding aerosols with a high content of fluorine, potassium and soluble manganese compounds was established. This was proved by structural damages, such as atelectasis, emphysema, bronchiectasis in the lungs, dystrophic developments in the contractual myocardium, a sharp decrease in the luminescent intensity of the adrenergic terminals in the myocardium. All the welding dust samples did not display a fibrogenous activity in any degree. PMID- 2262152 TI - [Use of State Standards for insuring labor safety in the preparation of scientific-technical documentation on chemical production]. PMID- 2262153 TI - [Retrospective analysis of disability indices and assessment of expert testimony of work capacity in dust-induced bronchitis]. AB - The article deals with current issues and quality of the medical labour examinations (MLE) performed by MLE commissions, reveals the reasons accounting for discrepancies in MLE based on the data of the commissions and those of specialized clinics. A clinico-functional examination of 243 in-patient dust bronchitis cases established a late primary diagnosing of dust bronchitis as one of the reasons for invalidism. 3-rd group invalids were mostly workers with lengthy professional background but still before the retirement age, who needed social and labour rehabilitation. The main reason for the discrepancies lies in inadequate examination prior to the MLE commissions decision and prescription of invalidism to the patients with the initial stage of the disease basing on the social criterion. PMID- 2262154 TI - [Hygiene and health related certification of a workplace and its significance in the preservation of workers' health]. AB - The article provides an outline of the techniques in the hygienic assessment of working places, along with the practical application of the data received. The importance of the assessment technique for health improvement measures planning is also substantiated. PMID- 2262155 TI - [Assessment of protective properties of gloves used in manufacturing of fiber glass products]. AB - The article deals with an account of occurrence and specific features of protecting gloves' damages and contamination of their inner surfaces. The results proved that rubber and knitter gloves cannot protect the hands adequately and must be changed. PMID- 2262156 TI - [Selective method of gas chromatographic determination of higher mercaptans in the air]. AB - The contributors propose a new highly effective gas chromatographic technique of dodecyl mercaptan (both normal and tertiary) measurements in the working zone air with a plasma-photometric detector by changing the detecting parameters. The optimal temperature regime is proposed, along with the conditions for sample taking in the working zone area. The new technique is capable of detecting the microquantities of normal and tertiary dodecyl mercaptan in the air in combination with other chemical substances. PMID- 2262157 TI - [Physiologic-hygienic requirements for head covering protecting from cold]. PMID- 2262158 TI - [Contents of lead, cadmium and zinc in the urine of workers in lead industry]. PMID- 2262159 TI - [Study of the metabolism of beta-hydrotetrafluoroethyl ether of phenol]. PMID- 2262160 TI - [Toxicity of cesium iodide, sodium iodide and cesium iodide activated by sodium iodide]. PMID- 2262161 TI - [Cytogenetic effects of wide-range noise]. AB - Noise at 40-12,000 hz frequency and 100 dBA with maximums in medium and high frequency ranges, maintained for 3 months and 4 hours per day did not change the number of chromosome aberration cells in the spinal marrow, but decreased by 1,3 the number of the aberrant hepatocytes in male rats. This was apparently caused by the mitotic activity of the liver parenchyma and related elimination of the damaged cells. The noise maintained for 4 months caused an increase by 1,7 in aberrant hepatocytes. This cytogenetic effect is regarded as potentially dangerous. PMID- 2262162 TI - [Effectiveness of anti-noise lining, ear muffs and their combination under the effect of high-level impulse noise]. AB - The article contains a description of a new technique for assessment of the effectiveness of noise-protecting bushes and era-flaps against the intensive impulse noise of shooting a 105 mm cannon and heavy grenade cup discharges. The technique envisages a simultaneous measurement of the maximal noise pressure levels with a common microphone from the inside under the ear-flap. It was indicated that a simultaneous use of bushes and protecting ear-flaps was more effective, but still less than a summation effect of their individual noise protecting properties. PMID- 2262163 TI - [The spread of intestinal parasites among school-age children between 1952 and 1982]. PMID- 2262164 TI - [The role of the thyroid in the regulation of breeding and reproductive capability in domestic animals]. PMID- 2262165 TI - [Changes in immunity in tumors]. PMID- 2262166 TI - [Comparative radiographic and histopathologic study of the lumbar part of the spinal column]. PMID- 2262167 TI - [Endogenous hypnogenic factors]. PMID- 2262168 TI - [Homotransplantation of the ear drum and auditory ossicles in the treatment of conductive hearing loss]. PMID- 2262169 TI - Regulation of biosynthesis of thiolutin and aureothricin in Streptomyces kasugaensis. AB - L-Methionine and DL-ethionine decreased production of thiolutin and aureothricin in Streptomyces kasugaensis. In the presence of L-methionine the culture also produced 3-methylthioacrylic acid, 3-methylthiopropionic acid and 3,6-bis-(2 methylthioethyl)-2,5-dioxopiperazine. Production of the metabolites depended on the concentration of L-methionine in the medium. PMID- 2262170 TI - Population study of cell cycle in a continuous culture of Candida utilis. AB - The mean lengths of G1, S, G2 and M phases of the cell cycle were determined on the basis of the population distribution of Candida utilis grown in a continuous culture under steady-state conditions by using an original mathematical method. The length of the G2 phase was proportional to that of G1; the length of M was effectively independent of the growth rate. The length of S was proportional to the mean number of mitochondria in the cell. PMID- 2262171 TI - Colicins E7 and E8 degrade DNA in sensitive bacteria. AB - The primary target of colicin E7 in sensitive bacteria are their DNA molecules. In agarose gel electrophoresis of lysates of cells treated with colicin E7, both chromosomal and plasmid DNA bands disappear, in direct relation to E7 concentration and to the duration of treatment. DNA degradation is followed by a cessation of DNA synthesis. In E7-immune bacteria, no damage to DNA due to colicin E7 occurs. The mode of action of colicin E7 thus appears to be equal to that of colicin E2. Also, colicin E8 causes a distinct damage to chromosomal and plasmid DNA in sensitive, but not in immune bacteria. None of the colicins E1, E3, E4, E5, E6 or E9 has any influence on bacterial DNA. PMID- 2262172 TI - The effect of soluble glucan derivates on spleen colony-forming units in sublethally irradiated mice. AB - We examined the effects of 5 soluble derivatives of yeast glucan on the formation of exogenous (CFU-S) and endogenous (E-CFU) colony-forming units in the spleens of sublethally irradiated (60Co, 6.5-7.0 Gy) mice of two inbred strains. For the estimation of CFU-S, glucans were administered intravenously either to donors or recipients of spleen cells 24 h prior to irradiation or removal of the spleen. The number of CFU-S was increased when both the donors and recipients were treated with glucan; the highest increase was obtained with glucans S, P and K. All glucan preparations increased significantly also the number of E-CFU even when administered 90 min after irradiation. There exist differences in the response to the stimulatory effect of glucans among individual mouse strains. Thus, for example, the stimulatory effect of glucan KM on the E-CFU number was significantly more pronounced in strain A/Ph than in strain C57Bl/6. PMID- 2262173 TI - Vocalizations of adult gelada baboons (Theropithecus gelada): acoustic structure and behavioural context. AB - Vocalizations and accompanying behaviors of adult gelada baboons were studied in four one-male groups kept in large outdoor enclosures in the zoos of Stuttgart and Rheine. Twenty-two acoustically different vocal patterns were determined. According to behavioural context, they were grouped into two categories: (1) contact calls and (2) aggressive and defensive calls. Frequency of calling and the production of different vocalizations were related to social rank and to the age of the sender. Vocalizations in species of the closely related genera Papio and Macaca are compared and their evolution is discussed. PMID- 2262174 TI - Behavioral responsiveness to strangers in young chimpanzees (Pan troglodytes). AB - Earlier studies of responses of primate infants to strangers were frequently confounded with separation from the attachment figure and/or removal to an unfamiliar setting. In the present study, young chimpanzees were tested in a familiar setting with a human female caretaker who served as an attachment figure. Two strangers were introduced: a human female, approximately the size of the caretaker, who refrained from initiating interactions and a larger human male, who repeatedly approached and initiated contact with the subjects. A somewhat more intense response was elicited by the larger, more assertive male stranger, but neither stranger elicited severe distress. The behavior of the chimpanzees is better described as wary, rather than fearful. These results may be attributable to the continued presence of the caretaker in contrast to previous studies reporting severe distress to strangers when chimpanzees are tested alone. A wariness of strangers in nursery-reared chimpanzees may develop by 6 months of age and may diminish somewhat by 2 years of age under the conditions of this study. PMID- 2262175 TI - Handedness of capuchin monkeys. PMID- 2262176 TI - Seasonal variation of the seminiferous epithelium cycle in Mayotte's brown lemur (Eulemur fulvus mayottensis). PMID- 2262177 TI - Loud calls of male purple-faced langurs (Presbytis senex). PMID- 2262178 TI - [The friction behavior of the ceramic bracket in arch wire-guided tooth movement]. AB - In spite of their wellknown disadvantages ceramic brackets are in great demand by orthodontic patients because of their aesthetic features. The amount of friction produced during tooth movement when a ceramic bracket slides along an arch wire, is still unknown. Using a custom-made friction test device the current study was undertaken to measure friction values of brackets of different manufactures with an 0.018 inch slot sliding along an 0.016 x 0.022 inch stainless steel arch wire. The results of this study showed that stainless steel brackets had slightly lower values than polycrystalline ceramic brackets. The monocrystalline bracket however showed significant greater friction values than both stainless steel and polycrystalline brackets even though its surface, as revealed with the scanning electron microscopy, proved to be quite smooth. PMID- 2262179 TI - [Experimental research on temporomandibular joint function in dysgnathic patients]. AB - In an experimental study we examined the function of the TMJ of patients with a considerable aberration from ideal dynamic occlusion and with obvious symptoms of frontal dysgnathia. Using a measuring seat for the simultaneous recording of opening and closing movements without occlusal interference and the sounds produced by the TMJ, we could not find any significantly impaired TMJ function compared with an orthognathic control group of similar age. PMID- 2262180 TI - [Experimental bodily tooth movement through the bony floor of the nose--a pilot study]. AB - Our experiment on animals was carried out in order to show to which degree the dog's bony nasal floor--taken as an equivalent of the recessus of the human maxillary sinus--is an obstacle to bodily tooth movement. The metric analysis showed that the movement of the upper teeth in comparison with the teeth of the lower jaw was markedly impaired by the basal cortical bone of the cavum nasi. Extended resorption of the basal bone of the nose was found histologically. The pressure side of the root surface too showed resorption lacunae which reached into the dentine deeply and were bordered by some osteoclasts. PMID- 2262181 TI - [A technic for cementing orthodontic bands; SEM research on the enamel and filling damages and a protective wax technic to avoid them]. AB - Damage of enamel and filling margins occurs during the removal of zinc phosphate cement with hooks and scalers after band cementation. This was revealed by scanning electron microscopy in different stages of the study in vitro and in vivo. When glass ionomer cement was used, and although the surplus cement was wiped off still being plastic, it could not be avoided that cement was wiped into the fissures and stuck to the slopes of the cusps. A protection of the occlusal surface with wax as described in this study is helpful for both using glass ionomer and zinc phosphate cement. Contamination of the occlusal surface with cement is avoided, and the isolating effect reduces the necessity to scratch off cement surplus. PMID- 2262182 TI - [Vertical changes in the lateral teleroentgenographic image after functional orthodontic therapy]. AB - We looked for vertical changes in lateral cephalometric X-rays of patients who had been treated with Andresen and Haupl appliances to correct distal occlusion. Thus, a therapy using functional appliances for orthodontic correction has the following effects on the vertical proportions of the visceral cranium. 1. The alveolar processes show additional vertical growth in the area of the incisors of the upper jaw and the molars of the lower jaw. 2. In conjunction with 1, increased vertical growth of the anterior facial heights compared to the posterior facial height causes an opening of the bite which, however, is not significant in terms of the Jarabak ratio. 3. Functional therapy has an effect on the spina plane, and, in addition, causes active vertical growth in the area of both upper facial heights, i.e., of the entire nasomaxillary complex. This additional growth is a little bit more pronounced anteriorly than posteriorly. Therefore the effect of functional orthodontic appliances on the nasomaxillary complex seems to be more complex than previously believed. 4. We did not observe any additional growth in the area of the ascending rami and/or condyles of the lower jaw during activator treatment. Our studies showed that the influence of functional orthodontic therapy on the vertical growth of the lower jaw is rather insignificant; the significant vertical changes were seen in the area of the mandibular molars and of the anterior facial heights. 5. Our findings thus support the assumption that the main vertical effect of the activator can be described as a relative inhibition of the development of the nasomaxillary complex with simultaneous normal progression of mandibular growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262183 TI - [The dentition and jaw growth of 60 mono- and dizygotic twins between the ages of 10 and 18]. AB - 60 twins were investigated between the age of ten and 18 years to obtain information about inheritance of tooth-crown size and growth of alveolar bone. The results suggest genetically controlled interaction between tooth germs during their formation. The intrapair differences decrease between ten and 18 years for the alveolar bone diameters. This is an advise for stronger genetically influences in higher age and an etiological factor for relapse after orthodontic treatment. PMID- 2262184 TI - [A new procedure for profile prognosis in the surgical displacement of the maxilla and the mandible]. AB - One of the most important goals of combined orthodontic-surgical treatment is the harmonization of the soft tissue profile. For a reliable prognosis of the soft tissue profile after surgical intervention, the soft tissue response to hard tissue displacements should be analysed in regard to horizontal and vertical effects. The material consists of the pre- and postsurgical cephalograms of 40 patients who underwent a Le Fort I osteotomy, 54 patients with displacement of the mandible by means of a sagittal split (Obwegeser/DalPont), and 42 patients with combined upper and lower repositioning. In contrast with recent investigations, the analysis of the soft tissue response was not based on the conventional landmarks. Instead of this, changes of the entire soft tissue profile were analysed in relation with the underlying outline of the hard tissue. The processed material resulted in numerical data which permit the elaboration of a profile prognosis with distinction of horizontal and vertical effects also taking the error assessment into account. PMID- 2262185 TI - [A critical analysis of the SNA, SNB and ANB angles in assessing orthodontic treatments]. AB - The purpose of this longitudinal cephalometric study was to evaluate the influence of growth changes at nasion (N) on the position of the reference line NSL and consequently on the measurements of the angles SNA, SNB and ANB. Lateral head films from 46 orthodontically treated patients were evaluated over an average period of 3.7 years. The NSL reference line was defined with respect to growth changes at the N-point: A: no consideration of growth; B: consideration of growth in the sagittal plane; C: consideration of growth in the sagittal and vertical planes. The results showed that growth changes at nasion had a decisive influence on the position of the reference line NSL and thus also on the angles SNA, SNB and ANB. In order to avoid misinterpretations in the evaluation of orthodontic treatment results the growth changes at nasion must be taken into consideration. PMID- 2262186 TI - [Clinical significance of increased serum triglyceride concentrations]. PMID- 2262187 TI - [Focal liver lesion as an incidental finding. 1: Diagnostic management--procedure in sonographically echo-free tumors]. AB - The spread of diagnostic ultrasound has led to an increase in the incidental detection of lesions of the liver in patients with unrelated symptoms and no history of tumor disease. In this article, suggestions are made on how to proceed with the further diagnostic workup of such patients. In part 1 these suggestions are aimed at identifying patients who might benefit from further investigation, while at the same time avoiding unnecessary procedures. PMID- 2262188 TI - [GnRH analogs in gynecology. Possibilities for therapeutic use]. AB - Gonadotropin releasing hormone (GnRH) agonists are synthetic peptide analogues of the natural gonadotropin releasing hormone with a stronger and more prolonged effect than the natural GnRH. Repeated administration of GnRH agonists induces pituitary desensitization followed by a decrease in gonadotropin secretion and estradiol synthesis. Thus reversible hypogonadotropic hypogonadism is produced. Consequently, estrogen-dependent diseases can be treated successfully with GnRH analogues. The therapeutic results obtained in patients with endometriosis, leiomyoma, pubertas praecox, and metastatic breast cancer are discussed. Furthermore the contraceptive properties of GnRH analogues, and combination treatment with HMG to induce ovulation is reviewed. PMID- 2262189 TI - [Treatment of gallstone disease]. PMID- 2262190 TI - [Indications for the use of chlormethiazole ]. AB - Clomethiazol (Distraneurin) has decisively improved our therapeutic possibilities in delirium tremens. Furthermore, it has acquired a certain degree of importance in the treatment of agitation and sleep disorders in geronto-psychiatric patients. In the meantime, owing to the fact that doctors have been too ready to prescribe it for indications other than those mentioned above, a level of abuse of this substance--which has the potential for both psychological and physical dependence--has reached a point at which its usefulness threatens to become eclipsed. PMID- 2262191 TI - [First aid against animal venoms. 5: snakes]. PMID- 2262192 TI - [Depressive symptoms in psychosomatic pain syndromes]. AB - Two groups of patients with psychogenic pain syndromes were compared: in one group, pain was the sole major clinical complaint; in the other symptoms of depression also presented in addition to the pain. In both groups, the patient considers himself to be physically ill, despite the absence of organic findings. On the basis of the clinical examples, the psychodynamics of chronic pain is discussed with respect to primary and secondary epinosic gain, conscious and unconscious processes involving personal loss, proffered offences, desires and affects. In the absence of depressive symptoms, the psychological organization of pain can be understood as a substitution. Such a situation leads to a "stabilization" of the symptom and more prolonged chronicity than when depression presents at the same time, since in these patients, referral for psychotherapy is delayed. PMID- 2262193 TI - [Long-term experiences with moxonidine, a new antihypertensive agent]. AB - Monoxidine is a new antihypertensive agent that, as pharmacological studies show, reduces blood pressure by stimulating central presynaptic alpha-2-receptors. In this open multicenter trial, 141 ambulatory hypertensives were treated for 12 months with monoxidine. After a run-in placebo period the mean supine blood pressure was 172.7 +/- 15.0/103.2 +/- 6.0 mmHg. After an individual dose adjustment phase of 3 weeks starting from a daily dose of 0.2 mg monoxidine, the mean blood pressure decreased to 150.7 +/- 13.4/87.5 +/- 5.5 mmHg. In 96 patients, the blood pressure reduction was achieved within 3 weeks at a dose of 0.2 mg, while 52 patients required a dose of 0.4 mg. Over the 12-month treatment period, no tolerance to the drug developed. In 137/141 cases (97%), the drug was well or very well tolerated. At the state of treatment dryness of mouth was observed in 12.9% and lassitude in 4.8%. On discontinuation of monoxidine, blood pressure gradually increased. All in all, monoxidine proved to be well tolerated, reliable and safe in the long-term treatment of hypertension. PMID- 2262194 TI - [Turning points in American psychiatry of the 20th century]. AB - Sabshin describes three turning points in twentieth century American psychiatry. Following "the time of the Thirteen", the time of the founders of modern American psychiatry, the first turning point was marked by the rise of Meyerian psychobiology and had its peak impact during the second quarter of the twentieth century. In the post World War II years diverging therapeutic ideologies became dominant, including the important impact of psychoanalysis. But competing ideologies (e.g. in social and biological psychiatry) were of importance also. The most recent turning point was marked by the current surge of neuro-science and psychopharmacology along with empiricism and logical positivsm. It is predicted to peak in the middle of the current decade. Following the preceding demedicalization a remedicalization of psychiatry was the result. For the turn of the 21st century, as Sabshin predicts, a re-emergence of analogues of Meyerian psychobiology will take center stage, particularly concentrating on questions of coping and adaptability, on how the human being keeps himself healthy and sane during subsequent developmental stages as well as in the face of stressful life events. PMID- 2262195 TI - [Adolf Meyer and relations between German and American psychiatry]. AB - German psychiatrists do not have an easy access to Adolf Meyer. The reasons include: his influence on American psychiatry was mainly exercised by his personal influence; he did not have the gift of writing his important and influential ideas in a clear language; these ideas, furthermore, were scattered over great number of papers in a variety of periodicals; there is only one unsatisfactory (from the point of view of edition) collection of Meyers papers; no textbook of Meyerian psychiatry exists. There seems to be no German translation of any of Meyers papers. Meyer, who was always in close contact with German psychiatry and psychiatrists, transmitted their ideas to the American scientific public, although in a critical vein. His own psycho-biological or genetico-psychodynamic theory pointed to the importance of the biological and personality structure and its reactions, of how the patient reacts to which live events and which illness in his or her body contrasts to Kraepelins concept of self-sufficiency of the endogenous psychoses. Whereas DSM I und II had been moulded in Meyers spirit, DSM III led far away from it. PMID- 2262196 TI - [The Hinckley case and some sequelae for psychiatry]. AB - After John Warnock Hinckley jr. had fired shots at President Reagan and had severely injured three others, he was considered not guilty by reason of insanity and brought to a psychiatric hospital. The case caused an unprecedented public interest because the psychiatric testimonies were contradictory (schizophrenia vs. personality disorder). According to the known facts it is very unlikely that a German psychiatrist would have diagnosed Hinckley as schizophrenic. One of the sequels of the sentence was a lowering of the reputation of psychiatrists for their inability to arrive at clear diagnosis. Another sequel was to increase the funds for research in biological psychiatry. Still another sequel was an insanity defense reform bill. The scientific debate and public discussions continue. PMID- 2262197 TI - [Phaeohyphomycosis and hyalohyphomycosis]. PMID- 2262198 TI - [Acute renal failure associated with acute type A hepatitis with a mild liver damage]. AB - Acute renal failure associated with acute type A hepatitis was successfully treated with hemodialysis. Though acute renal failure is usually associated with severe liver damage of end stage cirrhosis or fulminant hepatitis, liver damage of our case was only slight. The etiology of the renal failure is discussed. PMID- 2262199 TI - Modern European cranial variables and blood polymorphisms show comparable spatial patterns. AB - Spatial patterns in cranial traits for modern European populations are compared with patterns described by Sokal et al. (1989) for blood polymorphisms. Spatial patterns in these variables are described from both one-dimensional and directional autocorrelation correlograms. Manhattan distances computed among one dimensional correlograms are used (1) to cluster variables with similar patterns and (2) to test the hypothesis that these clusters are to some extent accounted for by the type of variable. The one-dimensional correlograms for cranial traits do not show a significant contrast with either red cell antigens or the set of blood polymorphisms that excludes HLA. The only contrast that accounts for any of the cluster structure among one-dimensional correlograms is that between HLA and non-HLA variables. A cluster analysis of the directional correlograms demonstrates that cranial traits reflect patterns comparable to those for blood polymorphisms. This finding implies that patterns in cranial variables can be accounted for by the same, or similar, population processes as those inferred from patterns in blood polymorphisms. The implications of this finding for the likely origin of the northwest-southeast cline seen in some modern blood polymorphisms and modern cranial variables, but not in Neolithic cranial variables, are discussed. PMID- 2262200 TI - Common major gene inheritance of extreme overweight. AB - We studied 3925 individuals in 961 families to determine the mode of inheritance of overweight. As an index of overweight, we examined body mass index. Our analyses indicate that the most likely genetic model for susceptibility to overweight included moderate polygenic inheritance (34% of variance resulting from many genes with small effects) and common (21% frequency) recessively expressed major genes (a few genes with large effects on the individuals who possess them). Standard statistical criteria for accepting both polygenic and major gene inheritance were met, including tests of Mendelian transmission. These results suggest that recessive major gene inheritance of overweight may be common and that homozygosity for overweight susceptibility alleles often results in overweight. Clinical, biologic, and empirical observations all suggest genetic heterogeneity, that is, more than one predisposing gene. PMID- 2262201 TI - Evidence for maternal inheritance of female height in a British national sample. AB - Analyses of the height variation in a large contemporary British sample found evidence for maternal inheritance of female height, because the mother-daughter correlation coefficient was significantly higher than the father-daughter value. Further evidence for a maternal effect came from the comparison of the daughter's stature with the difference in parental heights. The maternal effect was estimated to be 1%. PMID- 2262202 TI - Immunoglobulin allotypes in several North American Eskimo populations. AB - Genetic data consisting of immunoglobulin testing (GM and KM) from 631 Eskimos from 5 populations are reported. These populations are Savoonga, Gambell (St. Lawrence Island), Wales, King Island, and Mckenzie Delta, Baffin Island. The GM and KM haplotypes are analyzed and compared to those occurring in Greenland, Canadian, Alaskan, and Siberian Eskimos and to other Siberian indigenous populations. These analyses suggest that during the peopling of the New World, four separate migrant groups crossed Beringia at various times. PMID- 2262203 TI - Gene frequencies and admixture estimates in four Mexican urban centers. AB - We studied 202 individuals from the city of Leon in Guanajuato state, 228 from Merida, Yucatan, 220 from Oaxaca, Oaxaca, and 257 from Saltillo, Coahuila, to learn the distribution of the ABO, MN, Rh, and Duffy blood groups, serum haptoglobin, albumin, and factor Bf types, and red cell hemoglobin and glucose-6 phosphate dehydrogenase types. With the gene frequencies obtained, we performed admixture measurements with a maximum likelihood method, obtaining a trihybrid model for black, Indian, and white ancestry with the following proportions: 0.084, 0.513, and 0.403 in Leon: 0.059, 0.512, and 0.429 in Merida; 0.018, 0.676, and 0.306 in Oaxaca; and 0.073, 0.547, and 0.380 in Saltillo. The general pattern has high Indian ancestry followed by white and black ancestry. This pattern is congruent with most other studies performed in Mexico, including the east coast, where Indian ancestry predominates despite a clear increase in the black contribution. PMID- 2262204 TI - Standardization of the twinning rate. AB - There is a great interest in comparing twinning rates. These comparisons can be performed between different time periods for a specific population, between different regions within the same country, and between different populations. However, there are several factors (maternal age, parity, urbanization, etc.) that influence the twinning rate. The most dominant one is maternal age, and because the age distribution of the mother varies, it is necessary to standardize the data to make these comparisons. If we want to compare the twinning rates in different countries, we have to face the problem that the composition of the data from different countries may differ to a great extent. The applicable method is determined by the data of the lowest quality. Often the available data do not allow the traditional (direct and/or indirect) methods of standardization. Under such circumstances other methods have to be used. Earlier, Fellman and Eriksson (1987) proposed and successfully applied a new method. In this article we discuss the standardization problem in more detail. We suggest different methods and apply them to different data on twinning from Australia, Finland, and Baden Wurttemberg (West Germany). The new standardization methods give standardized twinning rates similar to the rates obtained by traditional methods. It is noted that, irrespective of standardization method, changes in maternal age alone cannot explain temporal or regional variations in the twinning rate. Other factors that may raise or lower the twinning rate are decreasing parity, sociodemographic changes with increased communication, which causes the breakup of isolates, and deteriorating physical condition of mothers as a result of increased industrialization and urbanization. PMID- 2262205 TI - Kinship and mate choice in a historic eastern Blue Ridge community, Madison County, Virginia. AB - Potential mates analysis is difficult to apply to small historic populations that lack clear boundaries or regular vital event registration. Here I analyze the actual mate pool as an alternative way to identify causes of nonrandom mating when unmarried members are unknown. Factors influencing mate choice within a historic eastern Blue Ridge community in Madison County, Virginia, are examined for four marriage cohorts: 1850-1879, 1880-1899, 1900-1919, and 1920-1939. These factors include nuclear kin avoidance, preferred age differences between mates, and preferences for more distant kin. A simulation is used to recombine members of the cohort-specific pools of married individuals to generate the probabilities of various types of kin marriages. The pedigree and vital statistics data are derived from first-time marriage licenses filled by community members in Madison County from 1794 to 1939. The numbers of marriages examined for each cohort are 88, 120, 132, and 132, respectively; the mate pools constructed from the samples are viewed from the female perspective. The results generated by simulation on the actual mate pools consist of mean kinship coefficients, numbers of marriages between "allowed" kin types, and probabilities of these values when marriage is random with respect to kinship. The results indicate significantly high levels of inbreeding in all four marriage cohorts, primarily because of high levels of first-cousin marriages in the first three cohorts and of first-cousin once removed marriages in the 1920 cohort. The observed mating patterns are discussed in terms of the social history of the Blue Ridge community and restrictions of the data. PMID- 2262206 TI - Temporal trends in marital structure and isonymy in S. Paolo Albanese, Italy. AB - In the fifteenth century, after the Turkish conquest of the Balkan area, Albanian communities migrated to Southern Italy. I investigated temporal trends in isolation from 1820 to 1982 in one of these communities, the population of S. Paolo Albanese, Basilicata, which still uses the original language and religious rites. Marital structure is characterized by a high average frequency of village endogamy (75.2%). Among the exogamous marriages there is a preference for mates from Italo-Albanian settlements, with higher values in the 1800s. The distribution of marital distances reflects the positive assortative mating by ethnic community. The mean frequency of isonymous marriages was 9.01% from 1820 to 1982. These results indicate that total inbreeding from isonymy is a reliable indicator of isolation, showing temporal trends related to changes in endogamy. Fr accounts for the greater percentage of Ft in relation to the small population size and regularly decreases with time. The breakdown of isolation, as documented by the decrease in population size, endogamy, and inbreeding, is a recent feature (since 1960). PMID- 2262207 TI - Suprofen: its usefulness in the control of pain following surgical removal of impacted wisdom tooth. AB - The results of the present investigation have shown the usefulness of suprofen in the control of pain following surgical removal of impacted wisdom tooth. The regime of 200 mg. q.d.s. orally, was shown to be satisfactory in the control of postoperative pain. Pain was rapidly controlled by the 1st hour after ingestion and subsequently maintained at a low profile until is was completely abolished by the 8th hour of the postoperative period. PMID- 2262208 TI - Odontogenic keratocyst of the maxilla--report of a case. AB - An interesting case of odontogenic keratocyst of the maxilla, with its clinical, radiological and histopathological findings, is reported. Total cystectomy resulted in a complete cure. Its histogenesis is discussed. PMID- 2262209 TI - AIDS and HIV infection: an epidemiological overview. PMID- 2262210 TI - A new insight into adriamycin-induced cardiotoxicity. PMID- 2262211 TI - Special problems in Fontan-type operations for complex cardiac lesions. AB - Four patients with complex cardiac lesions, who underwent successfully a Fontan type of operation are presented, each case representing a particular problem in surgical management. The first exhibited displacement of a trileaflet straddling and overriding left atrioventricular valve in addition to tricuspid atresia, while the second one had unilateral lung perfusion. In the third case, a stenosis had developed near the origin of the right pulmonary artery, and pulmonary vascular resistance could not be determined prior to the definite palliation procedure, whereas the fourth patient presented with stenosis of the left atrioventricular valve. Surgery was planned after detailed evaluation of the morphologic and hemodynamic features by means of echocardiography and cardiac catheterization. Our results illustrate the common tendency to extend the limits for modified Fontan procedures, which also includes revision of the original criteria for selection. PMID- 2262212 TI - Dynamic exercise echocardiography of the left ventricle in physically trained children compared to untrained healthy children. AB - To evaluate the effect of physical training on left ventricular function, we investigated 52 children, aged 7 to 14 years, who had trained for endurance sports over a period of at least 1 year. The children (24 boys and 28 girls) were investigated echocardiographically during supine exercise on a bicycle at increasing work loads of 6, 9, 12 and 15 kpm/min/kg body weight. The parameters of left ventricular function (specifically fractional shortening and the velocity of circumferential fiber shortening; both these parameters corrected for heart rate) were evaluated before, during and after the test. The values obtained were compared to those in untrained children investigated in a previous study. Fractional shortening in trained children rose from 37 +/- 5% to 54 +/- 5%, and in untrained children from 37 +/- 4% to 46 +/- 4%. The velocity of fiber shortening in trained children rose from 1.27 to 3.15 circ/sec while in untrained children it increased from 1.25 to 2.53 circ/sec. Left ventricular contraction, therefore was significantly greater in trained than in untrained children during exercise. While untrained children increased their cardiac output in the first minutes of exercise mainly by elevating their heart rate, trained children increased simultaneously the stroke volume. There were no significant differences between boys and girls, or between stages of maturity. Thus, physical training causes quick adaptations of left ventricular function to exercise in children of all ages. PMID- 2262213 TI - Endomyocardial fibrosis and the tuberous diet. PMID- 2262214 TI - AIDS cardiomyopathy: first rule out other myocardial risk factors. AB - Consecutive autopsies of 59 male AIDS patients revealed that 21 had other myocardial risk factors: 17 were alcohol abusers and 6 had hypertension or coronary artery disease. AIDS patients with these myocardial risk factors were older (mean age 45 versus 35 years, P less than 0.01), and were more likely to have cardiomegaly (mean heart weight 397 grams versus 350 grams, P = 0.06) than patients with AIDS alone. When evaluating patients for AIDS cardiomyopathy, other myocardial risk factors must be considered. PMID- 2262215 TI - Relation of complex ventricular arrhythmias to presenting features and prognosis in dilated cardiomyopathy. AB - To evaluate whether complex ventricular arrhythmias relate to presenting features and prognosis of dilated cardiomyopathy, 104 patients were studied from 1977 to 1987. At diagnosis, the 19 patients with complex ventricular arrhythmias (18%), as compared to the 85 patients without (82%), had a higher incidence of palpitation (P less than 0.01), severe dyspnea (P less than 0.001) and atrial fibrillation (P less than 0.01). They showed also higher mean right atrial pressures (10 +/- 5 vs 6 +/- 4 mm Hg, P less than 0.001) and higher right ventricular end-diastolic pressures (11 +/- 4 vs. 7 +/- 4 mm Hg, P less than 0.001) than patients without complex ventricular arrhythmias. Histologic samples were collected from the 32 patients (31%) studied since 1984 and semiquantitatively graded. The 11 patients with complex ventricular arrhythmias showed a higher frequency of severe interstitial fibrosis than the 21 patients without (64% vs. 24%, P less than 0.05), but they were otherwise similar as to the frequency of marked myocellular hypertrophy, changes of myocardial regression, endocardial fibrosis, attenuation of myocytes, hyperplasia of smooth muscle cells and infiltration by inflammatory cells. During a follow-up of 3.8 +/ 3.5 years, 35 patients (34%) died. Mortality was 58% (11 out of 19) in patients with complex ventricular arrhythmias and 28% (24 out of 85) in patients without (P less than 0.025). These results show that complex ventricular arrhythmias in dilated cardiomyopathy are associated with impairment of function of the right heart and severe interstitial fibrosis of the left ventricle, rather than with left ventricular dysfunction. Presence of complex ventricular arrhythmias also seems to identify those at high risk for death. PMID- 2262216 TI - Sustained beneficial effects of enalapril in Africans with congestive heart failure. AB - A single blind, placebo controlled, dose-ranging 3 month study of the effects of enalapril on cardiovascular parameters, clinical status and self-paced exercise capacity was undertaken in 12 Nigerians with chronic heart failure. Enalapril exerted only a modest reduction in blood pressure and heart rate but significantly improved functional capacity (P less than 0.01), and prolonged self paced exercise time (P less than 0.05) compared to the placebo baseline. The pressure rate product and the double product corrected for exercise time, an index of myocardial oxygen demand, exhibited a significant and sustained reduction on enalapril treatment (P less than 0.01). Concentration of sodium in the serum was significantly increased (P less than 0.05) but concentrations of potassium and creatinine were unaltered. These results demonstrate the sustained efficacy of enalapril in black Africans with heart failure and indicate no important racial difference in the response to inhibition of angiotensin converting enzyme in congestive heart failure. PMID- 2262217 TI - Influence of parental socioeconomic status on casual blood pressures of Nigerian school children. AB - The purpose of this study was to determine the effect of parental socioeconomic status on blood pressures of Nigerian school children. The weight, height, blood pressure and heart rate of 807 school children in Ile-Ife, Nigeria were measured. The subjects' ages ranged between 8 and 20 years. The subjects were classified into three (lower, middle and upper) groups based on the socioeconomic status of their parents. The findings revealed that parental socioeconomic status has no effect on the systolic and diastolic pressure, heart rate, rate pressure product and pulse pressure of Nigerian children. We found the 95th centile blood pressure to be 133/92 mm Hg. If the 95th centile is considered the diagnostic criteria for hypertension, then Nigerian children with sustained blood pressure in excess of 133/92 mm Hg should be investigated. PMID- 2262218 TI - Aneurysms of the atrial septum diagnosed by echocardiography and their associated cardiac abnormalities. AB - The association of atrial septal aneurysm and other cardiac abnormalities is reported in 14 consecutive cases diagnosed by cross sectional echocardiography. Color flow mapping was used in all cases in order to increase the accuracy in detecting associated lesions, especially small shunts at the atrial level. An atrial septal aneurysm occurred as an isolated lesion in just 1 patient (7%). In all other cases there was at least one associated cardiac defect. Atrial septal defect and prolapse of the leaflets of the mitral valve were particularly frequent, those lesions co-existing in half the patients. Although the lesion was not suspected clinically, physical examination, electrocardiography and chest X rays were abnormal in several patients, with a high incidence of electrocardiographic abnormalities and supraventricular arrhythmias in the overall group. PMID- 2262219 TI - The influence of isosorbide dinitrate and molsidomine on migration of polymorphonuclear neutrophils in vivo. AB - There is evidence that accumulation of polymorphonuclear neutrophils exacerbates injury to the tissues during acute myocardial infarction. To evaluate the influence of the vasodilator drugs, isosorbide dinitrate and molsidomine on migration of polymorphonuclear neutrophils, the "skin chamber" method was used. The number of neutrophils harvested from the chamber after oral treatment with isosorbide dinitrate increased from 27.65 +/- 9.02 X 10(6)/cm2 to 69.08 +/- 11.41 X 10(6)/cm2. Migration of neutrophils after molsidomine did not change significantly. Both drugs exert a similar effect on vascular smooth muscle cells. The difference in the influence on migration of granulocytes might be the result of an additional effect of molsidomine on formation of thromboxane and/or effects on the lipoxygenic pathway of arachidonic acid. PMID- 2262220 TI - Gross tricuspid incompetence due to isolated tricuspid valve prolapse. AB - We report a case of isolated prolapse of the tricuspid valve producing gross incompetence as documented by Doppler examination. This case shows that hemodynamically significant tricuspid regurgitation can occur from isolated prolapse of valvar leaflets. PMID- 2262221 TI - Haemochromatosis presenting as severe cardiac failure in a young adolescent. AB - A 13-year-old girl, who presented almost moribund in severe heart failure, was shown to have haemochromatosis. Repeated venesection has led to return of normal cardiac function. This adolescent would appear to be the youngest patient described with haemochromatosis whose initial presentation was that of congestive cardiac failure. PMID- 2262222 TI - Gaining, maintaining, and surveying competence in the interventional cardiology laboratory. PMID- 2262223 TI - Solitary aorta with bilateral ductal origin of non-confluent pulmonary arteries in pulmonary atresia with intact ventricular septum. AB - We report an exceptional case of pulmonary atresia with intact ventricular septum in which non-confluent pulmonary arteries were supplied by bilateral arterial ducts, the existence of which had been diagnosed in life. One should be aware of this arterial pattern, even when the ventricular septum is intact in the setting of pulmonary atresia, because it requires a different surgical approach than when atresia is associated with a ventricular septal defect, namely construction of bilateral shunts for palliation followed by reconstitution of the pulmonary arterial confluence for definitive repair. PMID- 2262224 TI - Three anomalies of the coronary arteries co-existing in a case of pulmonary atresia with intact ventricular septum. AB - A female infant, who died 17 hours after spontaneous birth, was found to have three distinct coronary arterial anomalies in association with pulmonary atresia with intact ventricular septum. These anomalies were first, an aneurysmal left coronary artery with a fistulous communication into the right ventricle; second, an anomalous origin of the right coronary artery from the pulmonary artery; and third, a supernumerary coronary artery arising from the right ventricle. Although the coronary arterial system was entirely connected to the right ventricle, the perfusing blood originated from the left ventricle and there was no clinical or histological evidence of significant myocardial ischaemia. PMID- 2262225 TI - Abolishing a sinus arrest resistant to atropine by aminophylline. PMID- 2262226 TI - Relationships of body size, segmental dimensions, and ponderal equivalents to muscular strength in high-strength and low-strength subjects. AB - There are conflicting results in prior studies concerning the relationships among body size, muscle size, and muscular strength. The purpose of the present study was to evaluate how body size, body shape, and segmental dimensions related to individual differences in muscular strength. Subjects were tested on four dynamic measures of strength and then classified into one of two groups as high strength (HS; N = 21) and low strength (LS; N = 21). Individual differences in strength were then related to body composition and segmental anthropometry. Strength was assessed during high-resistance, low-velocity standing squat and supine bench press with an isokinetic dynamometer, and during seated bench press and knee extension with a hydraulic resistance dynamometer. Anthropometry and body composition included 11 girths, six fatfolds, predicted fat-free mass (FFM), thigh and upper arm volume, muscle + bone cross-sectional area (CSA), and the Behnke Ponderal Somatogram (PSom) body profiling system. There was a 21.3% difference in strength between HS and LS (p less than 0.05), but no significant differences in age, stature, and fatfolds. MANOVA revealed that seven of 11 girth components of PSom were larger for HS (p less than 0.05). The correlations between strength vs body mass, FFM, thigh and upper arm volume, and CSA and fatfolds in HS and LS ranged from r = -0.52 to 0.56 (r = -0.70 to 0.70 when corrected for restriction of range). We conclude that individual differences in muscular strength are poorly related to various measures of body size and segmental body dimensions. PMID- 2262227 TI - A comparison of the effects of measured, predicted, estimated and constant residual volumes on the body density of male athletes. AB - The aim of this study was to use the measured residual volume (RV) of male athletes (n = 207) as a criterion and assess the error in their RV, body density (BD) and relative body fat (%BF) associated with using RVs predicted from regression equations, RVs estimated from vital capacity (VC) and an assumed constant RV of 1300 ml. The ventilated residual volume (RV) was determined both before and after the underwater weighing by helium dilution with the subject immersed to neck level. The mean of the absolute differences Idl and SEE between the 2 RV trials were 66 and 89 ml, respectively. These increased to values ranging 195-747 and 259-308 ml, respectively, when the means of the 2 RV trials for each subject were compared with the RVs predicted via regression equations, estimated from the VC and assumed to be a constant of 1300 ml. A similar trend emerged with variation of only the RV in the BD formula for each subject. The 2 RV trials resulted in a Idl and SEE of .00109 (.5% BF) and .00145 g.cm-3 (.6% BF), respectively, but these increased to values ranging .00306 (1.3% BF)-.01207 (5.1% BF) and .00394 (1.7% BF)-.00441 g.cm-3 (1.9% BF), respectively, for predicted, estimated and assumed constant RVs. In all cases the lowest Idl and SEE were associated with the RVs predicted by a multiple regression equation (R = .616; SEE = 259 ml) which was generated on our sample.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262228 TI - Changes in selected blood measures during repeated days of intense training and carbohydrate control. AB - Ten runners were studied to determine whether selected blood measures were useful indices of the metabolic stress associated with intense training and dietary carbohydrate (CHO) deficiency. The runners performed two diet/training regimens, involving 5 repeated days of intense training approximately 80 min/d, approximately 80% VO2max) and dietary CHO control (8.0 g.kg-1.d-1, EQ-CHO; 3.9 g.kg-1.d-1, LO-CHO). Resting blood samples were obtained after a 3-day control period, after 3 and 5 days of intense training, and after 3 days of rest. Resting uric acid levels were significantly higher (P less than 0.05) after 3 and 5 days of training during the LO-CHO vs EQ-CHO regimen (353 +/- 21 vs 309 +/- 24, and 345 +/- 26 vs 302 +/- 26 mol.l-1, respectively). Resting thyroxine (T4) levels were higher (P less than 0.05) after 5 days of training during the LO-CHO vs EQ CHO regimen (102.2 +/- 6.2 vs 83.7 +/- 4.5 nmol.l-1, respectively). While creatine kinase levels were elevated after both regimens (P less than 0.05), there was no difference between regimens. Serum cortisol (C) levels were reduced by 10% for both regimens (P less than 0.05), possibly due to an expansion in plasma volume (7.6 and 7.3% for the LO-CHO and EQ-CHO regimens, respectively). Resting FFA levels were increased (P less than 0.05) during both regimens, but there was no difference between the regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262229 TI - The contribution of passive drag as a determinant of swimming performance. AB - The purpose of the present investigation was to evaluate the contribution of passive drag (Dp) to the prediction of a 400-m swim. A second aim was to evaluate the relation between Dp and some anthropometric factors. In a first experiment, 84 swimmers (both sexes) had their Dp (at 1.4 m.s-1) and VO2max measured in water and put into relation with the performance time of a 400-m swim. Performance times were mainly related to VO2max (r = 0.70 and 0.72, p less than 0.01, for male and female swimmers, respectively). Inclusion of Dp as a second variable improved significantly (p less than 0.01) the accuracy of the regression up to 0.75 and 0.78. Passive drag was also significantly (p less than 0.01) related to height (r = 0.80 and 0.60, p less than 0.01, for male and female swimmers, respectively), weight (r = 0.78 and 0.54, p less than 0.01, for males and females, respectively), and body surface area (r = 0.80 and 0.58, p less than 0.01, for males and females, respectively). In a second group of 7 male swimmers, it was found that Dp values were increased on average by 34% (p less than 0.01) when measured after a maximal expiration as compared to measurements after a maximal inspiration. In a third group of swimmers (n = 41) for which generalized joint laxity was measured, it was found that this variable contributes significantly to the Dp variability. The present results show that Dp can be considered as contributing significantly to prediction of performance in swimming.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262230 TI - Prediction of lactate threshold (LT) and fixed blood lactate concentrations (FBLC) from 3200-m running performance in women. AB - The present study evaluated the accuracy of predicting velocity and oxygen consumption (VO2) at the LT lactate threshold and FBLC fixed blood lactate concentrations from a 3200-m time trial in women. Forty-four women (mean age = 31.1 yrs, mean ht = 164.9 cm, mean wt = 65.0 kg) completed a treadmill protocol for the determination of LT and FBLC and a 3200-m time trial. Velocity and VO2 values at LT, FBLC of 2.0 2.5, and 4.0 mM, and peak were determined. Mean VO2 and velocity ranged from 27.8 +/- 10.8 ml/kg.min-1 at LT to 42.5 ml/kg.min-1 at peak and from 129.8 +/- 44.0 m.min-1 at LT to 187.0 +/- 52.4 m.min-1 at peak, respectively. Results indicated that a 3200-m time trial (mean time = 20.6 +/- 6.6 min) was a good predictor of VO2 and velocity at LT, FBLC, and peak. Correlation coefficients (using a quadratic model) for velocity ranged from R = 0.96 to R = 0.98 with SEE ranging from 9.0 to 13.1 m.min-1. Correlation coefficients for VO2 ranged from R = 0.94 to R = 0.96 with SEE ranging from 2.8 to 3.6 ml/kg.min. The validity of these regression equations was examined in 13 women who completed a 12-month running program (VO2 LT, VO2 at FBLC of 2.0, 2.5 and 4.0 mM, and VO2 peak increased by 34.7, 19.9, 16.9, 11.9, and 5.4%, respectively, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262231 TI - Heart rates, cardiac arrhythmia, lactate levels and catecholamine excretions in CHD patients during cross-country skiing. AB - We examined cross-country skiing-related strain in 10 less experienced postinfarction patients, performing a skiing test, covering a distance of approximately 7 km in 90 min. Heart rates, cardiac arrhythmia, lactic acid levels and catecholamine excretions were determined as strain indicators. The patients' exercise capacity, estimated during graded ergometric cycling, was 2.1 +/- 0.4 watts.kg-1, indicating a nearly age-appropriate submaximum performance ability. They had suffered myocardial infarction 2.8 +/- 0.7 years previously, participated regularly in a rehabilitation program for at least one year, and they did not show coronary insufficiency or significant cardiac dysrhythmias during laboratory testing under their usual medications. They went cross-country skiing during a 4-day instruction period and subsequently performed a cross country skiing test on the 5th day. Mean skiing-related heart rates (124 +/- 9 bpm) and adrenaline excretions (124 +/- 88 pmol.min-1) corresponded on average to an exercise level of 1.85-2.0 watts.kg-1 during laboratory testing, and mean noradrenaline excretions (586-343 pmol.kg-1) and lactate concentrations (3.83 +/- 2.18 mmol.l-1) to a level of 1.48-1.73 watts.kg-1. Cardiac dysrhythmias were observed in a moderate number of 6-8 SVES, 9 to 12 VES and 4 to 7 couplets of VES per 1000 beats during cross-country skiing. The present results point to a comparatively high cardiovascular strain in less experienced postinfarction patients during a cross-country skiing test at an intensity level thought to be moderate. PMID- 2262232 TI - Ascending aortic blood flow dynamics following intense exercise. AB - The purpose of this study was to compare and contrast aortic blood flow kinetics during recovery from intense aerobic (maximal oxygen uptake test) and anaerobic (Wingate anaerobic power test) exercise. Fifteen healthy male subjects (VO2max = 56.1 +/- 5.8 mk/kg/min) participated in this study. Beat-to-beat peak aortic blood flow velocity (pkV) and acceleration (pkA) measurements were obtained by placing a 3.0 MHz continuous-wave ultrasonic transducer on the suprasternal notch at rest and during recovery (immediately post-exercise, 2.5 min, and 5.0 min) following the two exercise conditions. Peak velocity and acceleration significantly increased (p less than 0.01) from rest to immediately post-exercise and remained elevated throughout the 5-min recovery period. No differences were observed between the aerobic and anaerobic tests. Stroke distance significantly declined (p less than 0.01) immediately following exercise and progressively rose during the 5-min recovery period. The results indicate that: 1) aortic blood flow kinetics remained elevated during short-term recovery, and 2) intense aerobic and anaerobic exercise exhibit similar post-exercise aortic blood flow kinetics. PMID- 2262233 TI - Topical indomethacin in overuse injuries in athletes. A randomized double-blind study comparing Elmetacin with oral indomethacin and placebo. AB - In this double-blind trial in 70 athletes with superficial overuse injuries, the effect of topically and systemically administered indomethacin was compared with a placebo control. The treatment period was 2 weeks and blindness was secured by the double-dummy technique. The basic data of the patients showed no significant differences on entry to the study. The majority of cases were acute or subacute, the mean duration of symptoms being 7.4 weeks. The results showed a marked therapeutic effect after 3-7 days of treatment and statistically significant differences between the topical formulation and the placebo were reached in the parameters patients assessment of improvement and pain in connection with daily activity within the first week of treatment. However, during the second week the statistical significances were lost. Only in the topically treated patients local adverse reactions were observed. In the oral indomethacin group all reactions were systemic, GI- and CNS-complaints being predominant. The results on efficacy as well as adverse reactions favour the use of topical indomethacin in superficial overuse injuries in athletes. PMID- 2262234 TI - Long- or short-acting anesthetic with corticosteroid in local injections of overuse injuries? A prospective, randomized, double-blind study. AB - A prospective, randomized, double-blind study of 56 patients presenting with an overuse sports injury was undertaken in order to compare the effect of a long acting anesthetic (bupivacaine) with a short-acting anesthetic (lidocaine) in local corticosteroid injections. At presentation, patients were either administered a periarticular injection of 2 ml of methyl prednisolone acetate with bupivacaine (MPA-B) (40 mgs per ml + 5 mgs per ml) or 2 ml of MPA with lidocaine (MPA-L) (40 mgs per ml + 10 mgs per ml). No other treatment was given. Results indicated that pain inhibition was better in the MPA-B group during the first six hours after the injection, obviously because of the longer half-life of bupivacaine. In later evaluations no differences could be observed: in both groups pain disappeared partly or completely in two-thirds of the patients and full recovery to sports was possible in half of them. Long-acting bupivacaine is recommended as an anesthetic substance in local steroid injections of musculoskeletal overuse injuries. PMID- 2262235 TI - The influence of sex hormones on the plasma activity of muscle enzymes. PMID- 2262236 TI - Epidemiology and the European community. PMID- 2262237 TI - Population density and cancer mortality differentials in New York State, 1978 1982. AB - Patterns of cancer mortality within five population density quintiles in Upstate New York (New York State, exclusive of New York City), were investigated between 1978 and 1982. Sex-specific standardized mortality ratios (SMRs) were calculated within each population density quintile for all cancer deaths combined and for site-specific cancer deaths based on cancer mortality patterns exhibited by the general population of New York State, exclusive of New York City. Areas with the highest population density demonstrated a 12% excess of cancer deaths among males and a 6% excess among females. In contrast, areas with the lowest population density exhibited lower cancer mortality, among both males (9% less) and females (7% less). Males demonstrated a significant linear relationship between increasing population density and deaths for all cancer sites combined and for cancers of the oral cavity and pharynx, oesophagus, stomach, colon, gallbladder, pancreas, lung, prostate, and kidney. Among females, a significant linear relationship was observed between increasing population density and deaths for all cancer sites combined and for deaths due to cancers of the stomach, colon, liver and breast. Deaths due to cancers of the rectum, malignant melanomas of the skin, and cervix also exhibited unusual patterns of mortality across the population density quintiles. These data are most useful in generating hypotheses for further studies to define specific aetiological factors operating within population density groupings. Population density, as measured in this investigation, may represent a surrogate measure for other factors which are related to cancer morbidity and cancer mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262238 TI - Cancer incidence and risk factors among Montreal residents of Italian origin. AB - Cancer risks associated with Italian ethnicity were investigated using data from a large case-control study on the aetiology of several cancer sites in the male population of Montreal. Two approaches were taken. First, incidence rates were computed for Italians and for others in the Montreal area using our ascertained cases as numerators and census-derived denominators. Secondly, for respondents to the case-control study, an analysis was carried out with Italian ethnicity as the risk factor and a number of covariates as potential confounders. Out of 4553 incident cases in men aged 35-69, 301 were of Italian origin. As compared with other Montreal males, those of Italian origin had higher incidence rates for cancers of the stomach (p = 0.016, based on 31 cases) and of the colon and rectum (p = 0.102, based on 75 cases) and lower rates for cancer of the lung (p = 0.006) and prostate (p = 0.102, based on 24 cases). For other sites the differences between Montrealers of Italian and non-Italian origins were small. Montreal Italians manifested risks similar to those of the country of origin for cancer of the prostate and similar to the host country for cancers of the colon, rectum and liver. For other sites it was difficult to characterize the pattern because of wide variations among Italian registries. Over 80% of the study subjects in Montreal were interviewed and odds ratios (OR) for Italian ethnicity were estimated for each cancer site using all other sites as controls, adjusting for five potential confounders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262239 TI - The pattern of cancer in a large cohort of stroke patients. AB - A cohort of 113,732 stroke patients from Danish Hospital Discharge Registry were, by linkage to the Danish Cancer Registry, found to have developed a total of 5151 cases of cancer in a mean follow-up time of 2.4 years after the diagnosis of stroke. There was no excess of gastric cancer. The present findings fail to support the existence of a common, strong risk factor for stroke and gastric cancer in individuals. In the cohort, more cancer than expected was observed. In particular, a more than ten-fold increase in risk of brain tumours within the first year after stroke diagnosis was observed, suggesting some diagnostic misinterpretation of a brain tumour as a stroke. Minor excesses of cancer of other sites were also found in the first year of follow-up. They are probably due to increased medical surveillance and diagnostic misinterpretation of an underlying malignancy as an incident of cerebrovascular disease, eg through metastatic spread to the brain. PMID- 2262240 TI - The incidence of cancer among blood donors. AB - This study presents data on cancer incidence among 37,795 blood donors in an attempt to test the hypothesis that blood donation might be associated with cancer development. At a median follow-up time of nine years (range 5-13 years) a total of 1152 cancer cases have been diagnosed. The expected number of cancer cases derived from an age-matched population was 1459 giving a relative risk ratio (RR) of 0.79 (p less than 0.001). Calculations were made with and without latency periods between first blood donation and the diagnosis of cancer (0, 5, 10, 15 years). Overall, significantly decreased cancer incidence was observed (p less than 0.001) though the number of observed cases of haematological malignancies was not significantly different from that expected. For polycythaemia vera, however, the O/E ratio was 1.81 possibly indicating an association with blood donation. A more likely explanation is that this reflects increased diagnosis of polycythaemia vera in the blood donor population. PMID- 2262241 TI - Nitrate and nitrite exposure in Italian populations with different gastric cancer rates. AB - Exposure to nitrate and nitrite from dietary sources was estimated by questionnaire and measurement of salivary levels of the ions in residents of four regions of Italy with longstanding, contrasting, gastric cancer mortality rates. Whether using salivary levels or dietary questionnaire estimations no association was found between nitrate and nitrite exposure and gastric cancer mortality rates. For salivary nitrate and nitrite, the intra-provincial variation was greater than any inter-province difference. However, for dietary nitrate and nitrite intakes, there were significant differences between the regional groups (but not related to gastric cancer risk). Despite the limitations of the methods used, there was a weak positive association between salivary concentrations of nitrate and questionnaire assessment. Dietary factors are likely to play key roles at different stages of the gastric carcinogenic process. Nitrate may play a part but is unlikely to be a rate-limiting factor in all individuals or populations. PMID- 2262242 TI - Familial clustering of neural tube defects and gastric cancer. AB - A retrospective cohort study was conducted to determine whether producing an offspring with a neural tube defect (NTD) is associated with the development of unusual patterns of cancer among the parents in subsequent years. Mothers and fathers who had a child with an NTD in Upstate New York from 1945 to 1955 were followed through 1979 and compared to a control group of parents with normal offspring. Overall mortality and site-specific cancer incidence were not significantly different for case parents versus control parents, with the exception of gastric cancer, which occurred significantly more frequently in case parents. The finding of a familial association between NTDs and gastric cancer, coupled with a parallel decline in rates of these two diseases, suggests a common aetiology, perhaps related to dietary factors. PMID- 2262243 TI - Cutaneous malignant melanoma in females: the role of hormonal and reproductive factors. AB - The role of hormonal and reproductive factors as risks for cutaneous malignant melanoma (CMM) was explored by means of a population-based case-control study conducted in Turin, north-western Italy, on 186 female CMM cases and 205 controls. Past use of oral contraceptives (OC) did not seem to exert any effect on CMM risk odds ratio (OR) = 1.12, 95% confidence interval (CI): 0.56-2.24). No association was found even for the longest duration of use, for superficial spreading melanoma cases and for CMM of lower limbs only. While age at first birth did not affect CMM risk, women who had had three or more children seemed to be significantly protected as compared to nulliparous ones. The association was, however, substantially diminished by adjustment for education and other CMM risk correlates (OR for at least three children versus none = 0.62; 95% Cl: 0.29 1.31). PMID- 2262244 TI - Childbearing in marriage and mortality from breast cancer in Norway. AB - The relationship between childbearing and mortality from breast cancer has been studied in a cohort of 822,593 currently married Norwegian women with information on parity from the Census in 1970 and follow-up till 1985. All age groups of parous women showed significant trends of decreasing mortality rates with increasing parity. Nulliparous women had the same mortality rates as uniparous women in all age groups. In a stratified analysis, for age group 45-74 years, the relative risk for uniparous women was between 3.8 and 4.5 dependent on age at first birth compared to women with 8-9 children, age at first birth before the age of 25 and last birth after the age of 30 years. In a multivariate analysis age and parity were stronger risk factors than age at first birth, while age at last birth was nonsignificant. Among women 45-74 years the population attributable risk of breast cancer mortality due to childbearing was 72%, using women with 8-9 children as the reference group. The use of different definitions of reference group for parity is discussed. PMID- 2262245 TI - An epidemiological case-control study of breast cancer and alcohol consumption. AB - A case-control study of breast cancer and alcohol consumption was conducted with 1617 patients diagnosed with a primary cancer of the breast between 1982 and 1984 in 18 New York State counties. For each case, one control, matched for year of birth and county of residence, was selected from the driver's license files of the New York State Department of Motor Vehicles. Breast cancer risk was shown to increase as daily consumption of alcohol increased, with a risk of 1.37 (95% Cl = 1.07, 1.75) observed among women who consumed 15 or more grams of alcohol per day. Breast cancer risk did not appear to be related to the total number of years a woman drank or to be restricted to specific types of alcoholic beverages. The data suggest that this may be higher in women who began drinking at a later age. The increased risk associated with alcohol consumption, observed in the current study, persisted within strata of various breast cancer risk factors. PMID- 2262246 TI - Background gamma radiation and childhood cancers within ten miles of a US nuclear plant. AB - In light of some recent reports concerning childhood leukaemia near nuclear installations, we examined rates of cancer in children in relation to background gamma ray exposure. Data from a national monitoring programme around nuclear facilities were used to map the distribution of background gamma radiation for 69 small geographical subunits (average population 2300) within ten miles of one US nuclear plant. An association was found for incidence of childhood cancers as a whole (odds ratio (OR) = 2.4; 95% confidence limits (CL) 1.2, 4.6). For leukaemias specifically, the odds ratio was also elevated but confidence limits were very wide (OR = 2.4; 95% CL 0.5, 12.9). Analyses adjusting for sociodemographic characteristics of study tracts (population density and income) gave similar results; data on other risk factors were unavailable. Conventional risk models would not predict a detectable increase in childhood cancer from background gamma radiation, particularly not an increase of this magnitude. The large effect for solid tumours as well as leukaemias is also somewhat counter to expectation. Since a priori the association we observed was unlikely, it is important to know if similar trends in childhood cancer with background radiation are seen in other areas before rejecting chance or bias as an explanation for the result. PMID- 2262247 TI - Development of a record linkage protocol for use in the Dutch Cancer Registry for Epidemiological Research. AB - A method has been developed to determine the optimal linkage key for record linkage between the cancer registry and a large-scale prospective cohort study in the Netherlands. The proposed linkage procedure is a two-stage process in which the initial computerized linkage using a particular linkage key is followed by visual inspection with additional information to separate the computer matches into true and false positives. In the determination of the optimal key, both informativeness and susceptibility to error of personal identifiers were taken into account. The performance of the various keys in the linkage was expressed in terms of sensitivity and predictive value of a reported computer match. The key, consisting of date of birth, first four characters of the family name and gender was the optimal choice, with a sensitivity of 98% and an initial predictive value of a computer match of 98%. When additional information on migration, place of birth and first initial was collected in the second stage, it was possible to eliminate the false positives from the reported computer matches without loss of true positives. Thus, the sensitivity remained constant whereas the secondary predictive value of accepted matches was maximized. PMID- 2262248 TI - Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. AB - The relation between the plasma level of 25-hydroxyvitamin D3, the main metabolite of sun-induced vitamin D, and myocardial infarction (MI) was investigated in a community-based case-control study. Some 179 MI patients presenting to hospital within 12 hours of the onset of symptoms were individually matched with controls by age, sex and date of blood collection. MI patients had significantly lower mean 25-hydroxyvitamin D3 levels than controls (32.0 versus 35.5 nmol/L; p = 0.017), with the case-control differences being greatest in winter and spring. The relative risk of MI for subjects with 25-hydroxyvitamin D3 levels equal to or above the median was 0.43 (95% confidence limits = 0.27, 0.69) compared to subjects below the median. The decrease in MI risk associated with raised vitamin D3 levels was observed in all seasons. These results provide support for the hypothesis that increased exposure to sunlight is protective against coronary heart disease. PMID- 2262249 TI - The relationship between fat distribution and some chronic diseases in 11,825 women participating in the DOM-project. AB - The prevalence of reported chronic diseases was studied in quintiles of waist/hip ratio and Quetelet index in 11,825 women aged 40-73 presenting for mammographic screening in the DOM-project. After adjustment for age and Quetelet index, increased waist/hip ratio was found to be associated with an increased prevalence of diabetes mellitus, hypertension, cholecystectomy and a lower prevalence of varicose veins. No associations were observed between waist/hip ratio and the prevalence of angina pectoris, gout and rheumatism. The odds ratios, adjusted for age and Quetelet index, of the highest versus the lowest quintile of waist/hip ratio were 3.4 (95% CI 1.4-8.3) for diabetes mellitus; 2.2 (95% CI 1.7-2.8) for hypertension; 2.0 (95% CI 1.2-3.4) for cholecystectomy, and 0.81 (95% CI 0.68 0.95) for varicose veins. After adjustment for waist/hip ratio and age, Quetelet index was found to be associated with an increased prevalence of hypertension, cholecystectomy and varicose veins. Quetelet index, however, was not found to be related to diabetes, gout or rheumatism. We conclude that in a representative sample of Dutch women older than 40 years, fat distribution in addition to overweight is related to important chronic diseases. PMID- 2262250 TI - Relationship between adiposity and food intake: an example of pseudo contradictory results obtained in case-control versus between-populations studies. AB - Seemingly contradictory data support controversies concerning the relationships between food intake and illnesses. The present study of 1035 adults, aged 30-39 years, shows that (1) daily energy intake is not higher in obese than in non obese people, (2) obesity is more prevalent in social groups where energy intake is higher. These pseudo-contradictory results can be reconciled on the basis of a constitution/environment interaction. A comparison of groups based on presence or absence of illness (obesity, hypertension, coronary heart disease (CHD), cancer, etc) shows that some people can develop risk factors, even though their feeding behaviour is normal. This result (no direct relationship) underlines differences in individual susceptibility. When comparisons are made between populations with different diets the results (direct relationship) express environmental factors. The hypotheses on behavioural contribution to the aetiology of certain diseases appears more clearly in between-population comparisons than in case-control studies. Results of comparisons between populations (if the hypotheses they suggest are confirmed by intervention studies) warrant prevention at the level of populations, while results of case-control studies justify particular prevention in subjects at risk. PMID- 2262251 TI - Determinants of HDL-cholesterol and the HDL-cholesterol/total cholesterol ratio. Results of the Lubeck Blood Pressure Study. AB - Results are presented here on the relationship, in a large city in the Federal Republic of Germany, between HDL-cholesterol (HDL-C) or the HDL-cholesterol/total cholesterol ratio (HDL-C/TC) and the variables smoking, alcohol consumption, Body Mass Index (BMI), and age. The strength of each relationship is estimated and compared with the findings of other similar studies. Careful attention is given to the interactive effects of the variables. Evidence is presented to support, in a European setting, previous findings which suggest negative relationships between HDL-C or HDL-C/TC and certain lifestyle factors, namely BMI and cigarette smoking, and a positive relationship with alcohol consumption. In general, no relationship with oral contraceptive use or age is found. Several interactions among the various lifestyle factors and their relationships to HDL-C are seen, including a confirmation of a smoking/alcohol interaction found earlier. PMID- 2262252 TI - Consumption of boiled coffee is correlated with serum cholesterol in Finland. AB - The association between coffee consumption and serum cholesterol concentration was studied in a cross-sectional epidemiological study among 5704 men and women in Finland. The mean serum cholesterol values of those consuming boiled coffee (24% of the subjects) was significantly higher than that of drinkers of filtered coffee (69% of the subjects) in both sexes after adjusting for age, body mass index, smoking, serum gamma-glutamyltransferase, index of saturated fat intake, and physical activity: in men 6.37 versus 6.02 mmol/l, in women 6.22 versus 5.84 mmol/l, both significant at p less than 0.001. A significant dose-dependent effect was observed between the consumption of boiled coffee both in men and in women. For filter coffee drinkers a weak coffee dose-cholesterol association was found only for women. The magnitude of the effect of boiled coffee, 0.3-0.4 mmol/l in serum cholesterol values, is in accordance with the results from controlled trials carried out among both hyper- and normocholesterolaemic subjects. PMID- 2262253 TI - Black/white comparisons of deaths preventable by medical intervention: United States and the District of Columbia 1980-1986. AB - Blacks in the US experience increased mortality (1113 versus 745 per 100,000 males; 631 versus 411 per 100,000 females) and decreased life expectancy (63.7 years versus 70.7 years for males; 72.3 years versus 78.1 years for females); compared to Whites. In an effort to determine if the excess mortality among Black Americans might be explained by differences in access or quality of health care services, we performed a race-specific analysis of conditions for which mortality is largely avoidable given timely and appropriate medical care. Using methodology proposed by Rutstein and Charlton, mortality due to 12 causes was evaluated including tuberculosis, cervical cancer, Hodgkin's disease, rheumatic heart disease, hypertensive heart disease, acute respiratory disease, pneumonia and bronchitis, influenza, asthma, appendicitis, hernias and cholecystitis. In the US, during 1980 to 1986, an average of 17,366 deaths and 286,813 years of potential life (YPLL) before age 65 were lost each year due to all 12 sentinel causes combined. Of these causes, hypertensive heart disease, pneumonia and bronchitis, cervical cancer and asthma accounted for the greatest number of deaths. The mortality rate for all 12 causes combined among Blacks was 4.5 times that of Whites. The highest relative rates among Blacks compared to Whites were observed for tuberculosis, hypertensive heart disease and asthma. The overall mortality rate in the District of Columbia for the selected causes was 3.7 times the national rate. Compared to national rates, statistically significant elevated rates in the District were observed for tuberculosis, hypertensive heart disease and pneumonia and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262254 TI - Identifying maternal deaths in developing countries: experience in Jamaica. AB - Multiple sources were used to identify maternal deaths and their causes in a study carried out in Jamaica. These sources of information included a review of all deaths of women aged 12 to 49 years and included those occurring in hospitals (on maternity, surgical and medical wards and in casualty departments); reported to coroners' offices and the police; on whom post-mortems were carried out at hospitals, public morgues and for the Ministry of National Security; obtained from interviews with public health staff in all parishes and which were registered with the Registrar General's Department. Some 193 maternal deaths were identified giving a maternal mortality rate of 10 per 10,000 live births. No one source independently identified all maternal deaths. Hospital in-patient records yielded 133 deaths (69%), death certificates 74 (38%). Deaths due to certain causes were far more likely to be identified from particular sources eg those due to clinical mismanagement (complications of anaesthesia and blood transfusion) from hospital in-patient records; while deaths from ruptured ectopic pregnancy were more likely to come from coroners', police and morgue records. It is concluded that using multiple sources to identify maternal deaths in developing countries is an effective method to identify all maternal deaths. PMID- 2262256 TI - Respiratory history during infancy and childhood, and respiratory conditions in adulthood. AB - The aim of this paper was to study respiratory disorders in infancy and childhood as a risk factor for respiratory conditions in adulthood. During the first part of the survey 15,247 adolescents in the Bordeaux area (average age: 16.5 years, boys = 46.6%) filled in a self-administered questionnaire concerning their respiratory history during infancy and childhood, their present symptoms and their smoking habits. Each subject with chronic cough (n = 538) was then matched with two controls (n = 1094) and the parents of these subjects and of their controls were sent a complementary questionnaire. During the second part, 1807 adults (average age: 39.3 years; men = 49.7%) working at Bordeaux University filled in a self-administered questionnaire about their present respiratory symptoms, smoking habits and respiratory symptoms during adolescence. Spirometry was performed in 172 adolescents and 1665 adults. The results of the first part showed a very significant relationship in adolescents between respiratory history during infancy and childhood and current chronic cough even in non-smokers, non wheezers and non-asthmatics. The second part showed a very significant relationship in adults between respiratory symptoms during adolescence and present respiratory symptoms on the one hand, and a lower pulmonary function on the other, taking wheezing, smoking and asthma into account. In common with many similar studies, we conclude that respiratory disorders in young children may predispose to later disease, and that consequently it might be important to determine appropriate measures to prevent respiratory illness in childhood. PMID- 2262255 TI - Perinatal mortality in Matlab, Bangladesh: a community-based study. AB - Perinatal deaths, comprising stillbirths and deaths during the first week of life, were monitored over the eight-year period 1979 to 1986 in a rural Bangladeshi population of 196,000. The perinatal mortality rate was 75 per 1000 total births. The rate was 13% higher in males than females. Stillbirth and early neonatal mortality rates were 37 and 38 per 1000 total births, respectively. The major causes of perinatal deaths are presented, as well as some of the maternal determinants. During the period under study, perinatal mortality declined regularly and significantly over time in an area covered by an intensive Family Planning and Health Services programme, but not in the adjacent control area. This raises the issue of the impact of such a programme upon perinatal mortality, and the need to include a strong maternity care component into primary healthcare strategies if further reductions of perinatal mortality are to be achieved. PMID- 2262257 TI - Public health surveillance of non-infectious chronic diseases: the potential to detect rapid changes in disease burden. AB - The usefulness of surveillance in relating chronic disease trends to recent changes in risk exposures is often questioned on the grounds that these trends respond slowly, reflecting long periods between aetiological exposures and clinical onset of disease. We challenge this preconception on the basis of a review of several important risk factors and diseases: alcohol and liver cirrhosis; tobacco and stroke, cardiovascular disease, and lung cancer; and oestrogens and endometrial cancer. Data from cohort, cross-sectional, and modelling studies demonstrate that the time between removal of exposures and the onset of decline in morbidity or mortality is not defined by the time between initial exposure and disease occurrence. Rather, the pattern of lifetime exposures (with recent exposures often having a dominant effect), the dynamics of the disease process, and the segment of the population with reduced exposures determine how soon the decline begins. PMID- 2262258 TI - Measuring malnutrition in famines: are weight-for-height and arm circumference interchangeable? AB - Data from two surveys in Sudan have been used to examine whether weight-for height (WFH) and mid-upper arm circumference (MUAC) can be used interchangeably at a population level to define the proportion of children aged one to four years that are malnourished, whether they identify the same individual children as malnourished, and whether the relationship between WFH and MUAC varies with age. A MUAC cut-off of 13.0 cm consistently defined approximately the same proportion of children malnourished as 80% WFH in all seven groups of children examined, even though the proportion of children with less than 80% WFH varied between 8.6% and 30.7%. However, sensitivity/specificity analysis showed that many of the children identified as malnourished by the two indices were not the same individuals. Both the MUAC cut-off defining the same proportion malnourished as 80% WFH, and the sensitivity/specificity values, varied substantially with age. Studies of other populations have revealed both different MUAC cut-offs defining the same proportion of children malnourished as 80% WFH, and different sensitivities and specificities of MUAC relative to WFH. We do not recommend the direct comparison of data from surveys using WFH and those using MUAC. PMID- 2262259 TI - Usefulness of red cell distribution width in association with biological parameters in an epidemiological survey of iron deficiency in children. AB - The diagnostic usefulness of red cell distribution width (RDW) in association with usual biochemical and haematological parameters in detection of iron deficiency has been studied in a representative sample population of 384 children aged six months to six years in Reunion. Traditional parameters measured included serum ferritin (Fri), total iron binding capacity (TIBC), serum iron (SI), transferrin saturation (TSat), free erythrocyte protoporphyrin (FEP), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and haemoglobin concentration (Hb). RDW is an index of the variation in red cell size (anisocytosis). This recently derived parameter is measured by some models of electronic cell counter. It is not usually used in epidemiological investigations. Of the children studied, 13.6% had Hb less than 11 g/dl. The Pearson correlation coefficients between circulating iron parameters (SI, TSat, TIBC) or iron storage parameters (Fri) and RDW, MCV, MCH and FEP were greater than with Hb. The best correlations were observed for RDW, MCV and MCH with all other parameters. In this study, the upper limit value of RDW was defined as 18% using a Technicon model H-6000 counter. Other iron deficiency criteria were also defined and found to be in agreement with the international reference values for children aged six months to six years; MCV less than 70 fl, MCH less than 22 pg, MCHC less than 32%, FEP greater than 35 micrograms/dl whole blood, SI less than 6 mumols/l, TIBC greater than 85 mumols/l, TSat less than 10% and Fri less than 12 micrograms/l. The combination of sensitivity and specificity was best for RDW and worst for MCHC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262261 TI - Legume intake and gallstone risk: results from a case-control study. AB - As legume intake was recently shown to increase biliary cholesterol saturation, it may be a risk factor for gallstone disease. Data from a case-control study in The Netherlands were analysed to confirm this hypothesis. A negative association was found between legume intake (including green beans) and gallstone risk. This appeared not to be explained by diminished legume intake in gallstone cases under the influence of gastrointestinal symptoms. We hypothesize that components from legume pulses (seeds) and pods may have opposite effects on the risk of gallstone development. PMID- 2262260 TI - Epidemiology of carpal tunnel syndrome in women of childbearing age. Findings in a large cohort study. AB - There are few epidemiological data in the scientific literature about the carpal tunnel syndrome. This paper describes the characteristics of the 154 women referred to hospital for management of this condition among the 17,032 taking part in the Oxford-Family Planning Association contraceptive study. Standardized first referral rates for carpal tunnel syndrome doubled as age increased from 25 29 to 50 or more, tripled as smoking increased from zero to 25 or more cigarettes per day, doubled as total duration of oral contraceptive use increased from zero to ten years or more and doubled as Quetelet's obesity index (weight(g)/height(cm)2) increased from up to 1.99 to 2.6 or more. All these trends were statistically significant. Carpal tunnel syndrome was also found to be positively associated with a history of menstrual disorders, gastrointestinal tract symptoms and various orthopaedic conditions. The findings on cigarette smoking are of particular interest but require confirmation or refutation in another study before firm conclusions can be drawn. PMID- 2262262 TI - Lathyrism in rural northwestern Ethiopia: a highly prevalent neurotoxic disorder. AB - Lathyrism is a disorder of the central motor system, induced by heavy consumption of the grass-pea, Lathyrus sativus an environmentally tolerant legume containing the neurotoxic excitatory amino acid beta-N-oxalylamino-L-alanine (BOAA). A complete door-to-door resurvey of the Dembia and Fogera regions of northwestern Ethiopia, areas endemic for lathyrism, revealed an estimated mean disease prevalence of 0.6%-2.9%. Most patients developed the disease in the epidemic of 1976/77, although new cases appear to have occurred with an estimated mean annual incidence of 1.7:10,000. Production and consumption of grass-pea is increasing in Ethiopia, making attempts to develop low-BOAA strains to prevent lathyrism increasingly important. PMID- 2262263 TI - An epidemiological description of lightning-related deaths in the United States. AB - To better quantify and update the health impact of lightning and to compare potential sources of information, we reviewed data from the National Centre for Health Statistics (NCHS) database for 1968 through 1985 and from the North Carolina Medical Examiner (NCME) computerized database for 1972 through 1984. We epidemiologically characterized all lightning-related deaths identified in these databases. Results of our analysis are presented together with previously published information from the National Oceanic and Atmospheric Administration and from the National Institute for Occupational Safety and Health. In the US, Wyoming has the highest average annual lightning-related death rate (0.196/100,000), whereas Florida has the largest cumulative incidence of deaths (200) for this 18-year period. Death rates are the highest for males and for people 10-19 years old. There is a tendency toward a slight, but steady, decrease in the yearly incidence of lightning-related deaths. One-third of the fatalities are job-related. Both the NCHS and NCME databases are limited in describing the circumstances and aetiologies of these deaths. PMID- 2262264 TI - Ecological versus case-control studies for testing a linear-no threshold dose response relationship. AB - The two basic problems with ecological studies are (A) individuals studied are not necessarily the individuals who are at risk, and (B) they are very vulnerable to confounding factors. It is shown that where the study is designed to test a linear-no threshold dose-response theory, (A) does not apply. Where the ecological study deals with the average dose and response in a large number of US counties, the available data and computer capability for reducing effects of confounders are so powerful that (B) may be no more important for the ecological than for a case-control study. The migration problem is treated and found to be relatively unimportant. PMID- 2262266 TI - Geographical patterns of male circumcision practices in Africa: association with HIV seroprevalence. AB - To ascertain whether male circumcision might explain some of the geographical variation in human immunodeficiency virus (HIV) seroprevalence in Africa, we investigated the association between the practice of male circumcision at a societal level and HIV seroprevalence. Male circumcision practices for over 700 African societies were identified, and HIV seroprevalence in general adult populations from 140 distinct locations in 41 countries was obtained. In locations where male circumcision is practised, HIV seroprevalence was considerably lower than in areas where it is not practised. This study supports the hypothesis that lack of circumcision in males is a risk factor for HIV transmission. PMID- 2262265 TI - Evaluation of a village health worker programme: the use of village health worker retained records. AB - A village health worker (VHW) programme in a rural area in South Africa is evaluated, a year after the introduction of VHW-retained child record cards. The programme's success in promoting immunization and breastfeeding and the coverage of and contact with the community by the VHWs was investigated. A population survey on children under one year was matched to VHW records, showing that VHWs were reaching 70.8% of the target population. VHWs were more likely to visit a child with a Road to Health Card (RTHC) and who was born in the village. VHWs generally visit mothers once a month and make contact with most children in their first month of life. Children born before the start of the new VHW programme were compared with those born after, using survival analysis techniques and data from the RTHC on the first year of life of all children under two. An increase in polio immunization coverage was detected but there was a drop in measles immunization coverage. We conclude that a VHW-retained child record for the first year of life plays a valuable role in ongoing health care evaluation. PMID- 2262267 TI - Durability of passive measles antibody in Jamaican children. AB - Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries. PMID- 2262268 TI - Measles immunization strategies for countries with high transmission rates: interim guidelines predicted using a mathematical model. AB - This study addresses the problem of measles immunization in communities experiencing unacceptably high numbers of cases in young infants, under circumstances where high dose Edmonston-Zagreb vaccine is not yet available. Where the continued use of standard potency vaccines (eg Schwarz) is unavoidable we have investigated the merits of new policies which aim to offer better protection to children below the currently recommended vaccination age of nine months. These policies are intended for implementation in communities with intense measles transmission. Predictions, spanning five years, using a previously developed mathematical model are presented for two types of potential new policies: a 'switch' to a younger target age, or a 'two-dose' strategy incorporating vaccination at a younger age in addition to the current schedule at nine months. We conclude that a switch in immunization policy to a younger age is of doubtful worth, but that supplementary vaccination at around six months in addition to existing coverage at nine months (ie two-dose policy) is a desirable option. PMID- 2262269 TI - Efficacy of oral poliovirus vaccine in rural communities of North Arcot District, India. AB - The protective efficacy of three doses of oral poliovirus vaccine (OPV) was measured in children under five in the rural blocks of North Arcot District. In 1988, a sample survey of 7% of the total population of the district (population five million) was conducted to determine the immunization coverage with OPV and the incidence of paralytic poliomyelitis in under-fives in the previous 12 months, (n = 42,045). For every case of poliomyelitis, all children matched for exact age in months resident within the same block were taken as controls. Some 67 children had poliomyelitis (prevalence of lameness 1.59/1000, estimated annual incidence 2.57/1000 under-fives). Among cases and controls 24 and 42%, respectively, had received three doses of OPV, while 44 and 33% had received none. In a case-control analysis, the vaccine efficacy (VE) was 62% for all under fives; for the 12-23 months age group it was 71.4%. For a vaccine with the potential of near 100% VE, this is disappointingly low. Obviously, not only the immunization coverage level, but also the VE should be enhanced if poliomyelitis is to be controlled in India. This may be achieved by a five-dose OPV schedule, annual OPV immunization campaigns in addition to the routine three-dose schedule or by using inactivated poliovirus vaccine of enhanced potency. PMID- 2262270 TI - Rotavirus diarrhoea in Apache children: a case-control study. AB - A case-control study of rotavirus diarrhoea in Apache children up to two years old was conducted at the White Mountain Apache reservation from 1 May through 15 December 1985 to identify risk factors for rotavirus diarrhoea. The mothers of fifty cases, forty-five hospital controls and twenty-five neighbourhood controls participated in this study. Exposure to other children with diarrhoea stood out as the single most important factor for acquiring rotavirus diarrhoea (Odds ratio = 14.0). Other significant risk factors were living in homes with septic tanks and in homes with 'poor environmental sanitation.'. Minimizing contacts of children with diarrhoea therefore would be the most effective measure in preventing the spread of this disease in the community. PMID- 2262271 TI - Malnutrition is associated with increased diarrhoea incidence and duration among children in an urban Brazilian slum. AB - This study was undertaken to further define the relationship between malnutrition and subsequent diarrhoeal illness among children. A cohort of 61 children under five years of age was followed for two years in an urban Brazilian slum. Nutritional status was determined at two-month intervals and was used to predict the subsequent occurrence of diarrhoea. A significant, graded association between worsened nutritional status, as measured by length- or weight-for-age, and diarrhoea incidence was found. This relationship was present for both two-month and one-year periods following nutritional assessment. The average duration of diarrhoea was also significantly longer during the two-month periods which were preceded by the worst nutritional status. Overall, the most malnourished children had nearly twice the total number of days of diarrhoea that better nourished children had. These results provide additional evidence that a significant association between malnutrition and both increased diarrhoea incidence and duration exists. PMID- 2262272 TI - Is it possible to predict which diarrhoea episodes will lead to life-threatening dehydration? AB - Early detection of children who are likely to develop life-threatening dehydration as a consequence of diarrhoea would be of great value for health care workers in developing countries. We carried out a case-control study to compare the symptoms and signs observed on the first day of diarrhoea in two groups of 192 children aged under two years, in the Brazilian city of Porto Alegre. The cases were children admitted to a hospital with moderate or severe dehydration, and controls were children from the same neighbourhoods as the cases, who had diarrhoea which did not lead to hospital admission. The sensitivity and specificity of different clinical indicators were calculated. Alterations in thirst (82%), followed by six or more stools (71%), fever (60%), vomiting (58%) and loss of appetite (57%) had the highest sensitivities, whereas the specificities were largest for blood in the stools (97%), fever (78%) and vomiting (78%). Assuming that dehydration occurs in 5% of all episodes of diarrhoea, the use of fever as a screening criterion, or the use of vomiting, would select 24% of all children with diarrhoea, and capture about 60% of all episodes of dehydration. The combination of fever or vomiting would increase the proportion selected to 36%, and capture 75% of episodes of dehydration. PMID- 2262273 TI - A waterborne outbreak of leptospirosis among United States military personnel in Okinawa, Japan. AB - A waterborne outbreak of leptospirosis occurred among US military personnel during September 1987, on the island of Okinawa, Japan. Micro-agglutination titres for leptospiral antigen of greater than or equal to 200 were detected in hospitalized adult males averaging 22.5 years of age with symptoms compatible with leptospirosis. Epidemiological findings revealed two case clusters distinguished by time and place of exposure. The overall attack rates among recreational swimmers and combat skills training participants were 467/1000 (7/15) and 183/1000 (15/82), respectively. Swallowing of water differentiated individuals with laboratory-confirmed infection from those with no infection, while water immersion alone did not appear to result in leptospiral infection. Additionally, subnormal rainfall may have contributed to the risk of exposure associated with this outbreak. PMID- 2262274 TI - Mechanisms of influences on smoking and drinking behaviour among secondary schoolchildren. PMID- 2262275 TI - Draft guidelines on ethics for epidemiologists. PMID- 2262276 TI - Recent coronary heart disease mortality trends in Spain. PMID- 2262277 TI - Feasibility of ascertaining occupational histories from men over age 70 through self-administered questionnaires. PMID- 2262278 TI - The frequency of imperforate hymen in northern Italy. PMID- 2262279 TI - Ecological bias and confounding. PMID- 2262280 TI - Special supplement on Rapid Epidemiological Assessment (REA) PMID- 2262281 TI - [Avoidable years of life lost ratio: an indicator to identify excess mortality in health areas. Mortality workshop of the Valencia region]. AB - Avoidable mortality has been proposed as an outcome indicator of health services. Until now the Standardized Mortality Ratio (SMR) has been the effect measure most used to detect excesses in avoidable mortality. We propose the use, as a complementary measure, of the Avoidable Years of Life Lost Ratio (AYLLR). We show that for tuberculosis, hypertension and for all avoidable deaths both measures provide complementary information, since in some areas where observed deaths are below the expected number (SMR less than 100) we detect an observed number of years of life lost higher than expected (AYLLR greater than 100), due to the occurrence of these deaths at younger ages. The AYLLR is a standardized effect measure that puts a higher weight to premature deaths. PMID- 2262282 TI - [Usefulness of information leaflets about drugs for hospitalized patients with chronic diseases]. AB - To know how patients perceive the information leaflets about medicines, it has been carried out a study in a sample of 65 patients admitted to a hospital for chronic respiratory or cardiac diseases. A 47.7% of patients expressed that the main information provided by the leaflet was such concerning to the purpose of the drug, whereas a 18.5% pointed out such concerning to side effects and management of unexpected circumstances. Sixty three percent of patients expressed that leaflets did not provide them new information. A relevant percentage of patients did not know the meaning of some terms frequently used in leaflets and package-inserts (80% of mistakes in the interpretation of "take the drug on an empty stomach"). It is concluded that the information leaflets can be useful in the framework of a good physician-patient relationship, as a reminder, and to reinforce the knowledge that the patient already has. It is considered that the most appropriate time for the education of chronic patients about drugs is when the treatment is prescribed for the first time. PMID- 2262283 TI - [A morbidity information system based on school absenteeism]. AB - We present a pilot experience about the introduction of a information system designed for the knowledge of infant morbidity (4-15 years) in a 13 school week period in a representative sample of 60 schools of the Valencian Community. We studied school absences that lasted three days or longer. Reports of teachers and parents were the source of information (100% response rate). Medical certification was also requested to the pediatricians and general practitioners of the area of the schools (12.74% response rate). To test the validity of this information system, absences caused by hepatitis were compared with the registry of Notifiable Diseases System (NDS) for the same period. We recorded 3,968 absences, with a cumulative incidence of 100.68 per 1,000 (C.I., alpha = .05, +/- 4.97) for females, and 119.4 (C.I., alpha = .05, +/- 18.36) for males. These differences were statistically significant. There was a concordance of 80.25% of the hepatitis cases between the registry of absenteeism and that of the NDS (chi 2 goodness of fit test = 3.16, p = .754). Although absences shorter than 3 days were not taken into account, the information system provided relevant and valid estimates of morbidity. Moreover, collaboration of teachers was considered very positive, which led us to use this health information system in five health areas of the Valencian Community. PMID- 2262285 TI - [Translation of the term "odds ratio"]. PMID- 2262284 TI - [Nutritional risk factors for ischemic cardiopathy]. AB - The purpose of this review is to analyze original and review papers dealing with associations between diet and its influence on the incidence of Coronary Heart Diseases, so as its implications on the preventive measures at regional levels. It has been analyzed relationships between serum cholesterol levels and Coronary Heart Disease, diet and serum cholesterol and diet and Coronary Heart Disease. It is concluded that there have been shown strong relations in comparisons between communities. However, there are not consistent relations when subjects from the same community are compared. This could be due to variations in variable measurements, such as the limitations of the tools used (food survey, food composition tables, individual intake variations, etc.). All these would difficult to extrapolate the results from one region to another. To develop more effective preventive measures there is the need of cohort studies at regional level bearing in mine all that considerations above mentioned. PMID- 2262286 TI - [Relative opportunity: reflections about the translation of the term "odds ratio"]. PMID- 2262287 TI - [To translate or not to translate: is that the question?]. PMID- 2262288 TI - [Admission to treatment for opiate and cocaine consumption in Spain. Workshop of the State Information System on Drug Addiction]. AB - The State Information System for Drug Addiction (SEIT) was designed to monitor the magnitude of the abuse of opiates and cocaine by indirect indicators (treatment admissions, hospital emergencies and deaths). The notification of initiation of treatment started to run in all the Autonomous Communities (Comunidades Autonomas) during 1987. In this study we analyze the characteristics of 10,338 individuals who initiated a treatment for illegal drug abuse (opiates or cocaine) during 1987 in 224 centres spread along the Autonomous Communities and which had been notified to SEIT. 97.1% were heroin users, with a mean age of 24.8 years, basically males (80.5%) and who had been taking the drug which caused the treatment for the last 5 years. 69.4% reported having first time used heroin between 1980 and 1985. The absolute number of drug users who were treated in specific centres in the different Autonomous Communities allow us a first approximation to the magnitude of heroin addiction in Spain. Moreover, the data we present help to characterize this subgroup of the heroin population from the demographic and the consumption points of view. PMID- 2262289 TI - Catheterization of branchial sinus tracts. A new method. AB - The complete surgical extirpation of branchial cleft abnormalities is essential in avoiding recurrent disease. The most technically difficult maneuver is often the localization and excision of associated sinus tracts and fistulae. The authors communicate a simple yet effective technique for dealing with this difficulty utilizing the Fogarty embolectomy catheter. PMID- 2262290 TI - Fundamental voice frequency in female puberty measured with electroglottography during continuous speech as a secondary sex characteristic. A comparison between voice, pubertal stages, oestrogens and androgens. AB - The change of fundamental voice frequency in continuous speech in female puberty was analysed in 47 girls by comparison of 2000 consecutive electroglottographic cycles in a reading situation. The results were compared with serum concentrations of androgens (dihydroepiandrosterone, delta-4-androstenedione, testosterone, and sex hormone binding globulin), oestrogens (oestradiol, oestrone, and oestronesulphate), and somatic puberty (weight, height, mamma stages, and pubic hair stages). Fundamental frequency in continuous speech was related only to oestrone r = -0.34, (P less than 0.05). But the tone range in continuous speech and the lowest tone in the phonetogram were found to be significantly correlated with many of the pubertal and hormone parameters. All these correlations could be explained by a common age-dependency. By multiple regression analysis different sets of variables for prediction of speaking fundamental frequency were found before and after menarche. PMID- 2262291 TI - A young meningitically deaf child with a cochlear implant: a case study. AB - This study describes the development of the auditory, cognitive, linguistic, and social domains of a child deafened by meningitis at 20 months of age. He received a 3M/House cochlear implant at 27 months and is believed to be the youngest child to receive a cochlear implant. He was seen for intervention emphasizing audiometric conditioning and testing and language (speech and sign) stimulation for a period of 2:9 years (6 months pre-implant to 2:3 years post-implant). Videotapes of intervention; interviews with parents, teachers, and clinicians; test results; and medical and clinical reports were documented from pre-implant to two years post-implantation. The child regressed in all areas evaluated following his illness and subsequent deafness and cochlear implantation. At about one year after implantation, his social and cognitive skills began to improve. By two years after implantation (chronological age (CA) = 4:6), his abilities in all areas except auditory reception and speech had progressed to about the 4:0 age level. He communicates primarily through signs and seems to derive environmental sound and speech duration cues from the implant. Although it is difficult to separate the effects of the implant from maturational factors, he now willingly uses the implant simultaneously with his hearing aid on the non-implanted ear every day and seems to be functioning well with them. He responds inconsistently to his name when called, and consistently provides appropriate signed responses to questions. His imitative skills are improving; he can discriminate one- vs two syllable words; and produces limited spontaneous speech. His cognitive and social abilities are at least age-appropriate and he signs 3- and 4-word combinations. PMID- 2262292 TI - Early home management of patients with Pierre Robin sequence. AB - Robin Sequence is a well-described disorder with a reported incidence of 1 in 2000 births. It is characterized by glossoptosis and micrognathia often associated with a cleft palate. Respiratory obstruction at the level of the tongue occurs in many affected children. Prior to routine intensive care unit management, it was the primary factor in the mortality reported in patients with moderately severe to severe deformity. Treatment of this obstruction is controversial and may include a long stay in an intensive care setting. We report two cases that demonstrate properly placed and constructed nasopharyngeal tubes allow a non-surgical treatment with early discharge of the patient and without the risks and morbidity of surgery or the complications of tracheostomy. PMID- 2262293 TI - The preventive value of audiometric screening of preschool and young school children. AB - The routine to screen 4- and 7-year-old children with audiometry has been studied with regard to its preventive value. Out of 2,330 4-year-olds, 27 children with secretory otitis media (SOM) were treated with myringotomy and 9 of these with grommets as a consequence of identification by screening. One child with unilateral, sensorineural impairment received special teacher's assistance 2 h per week as a consequence of identification by screening. When the same children were screened at the age of 7, 6 children with SOM were treated with myringotomy after identification by screening audiometry. Children with SOM at the age of 4 had impaired hearing at the age of 7, identified by screening, 4 times more frequently than other children. The study suggests that audiometric screening in Sweden does not have important preventive effects on hearing impairments or on sequelae of auditory deprivation. PMID- 2262294 TI - Management of a large frontoethmoid osteoma with sinus cranialization and cranial bone graft reconstruction. AB - Osteoma represents the most common benign neoplasm of the nose and paranasal sinuses. The etiology of osteomas is uncertain and the majority occur in the frontal. ethmoid, and maxillary sinuses in that order. We present a 14-year-old male with a large frontoethmoid osteoma that required frontal sinus cranialization and pericranial bone graft reconstruction following removal. The osteoma recurred 6 months postoperatively and was excised. Treatment alternatives and a review of the literature are presented. PMID- 2262295 TI - Otolaryngologic manifestations of child abuse. AB - The number of reported cases of child abuse has increased dramatically over the past several years. Maltreatment of children can take several forms including neglect, sexual abuse, physical assault and psychological trauma. Five cases of child abuse presenting initially to the Otolaryngology Service are outlined: bilateral auricular hematomas, recurrent tympanic membrane lacerations, a pharyngeal laceration with retropharyngeal abscess and medical neglect of a patient with a parotid malignancy and one with laryngeal papillomatosis. Characteristic presentations and risk factors in family background are discussed toward the goal of early recognition and appropriate intervention. PMID- 2262296 TI - Peritonsillar abscess in Kawasaki disease. AB - Mucocutaneous lymph node syndrome, Kawasaki disease, is a potentially fatal pediatric disease characterized by prolonged high fever, conjunctivitis, stomatitis. myocarditis, aseptic meningitis and coronary artery vasculitis. We present peritonsillar abscess as a previously unreported otolaryngologic symptom and presentation of Kawasaki disease. A previously healthy 7-year-old boy required hospitalization for a peritonsillar abscess. Despite adequate surgical drainage and appropriate intravenous antibiotics, the patients' systemic symptoms persisted. After the week of hospitalization, the child was transferred to the intensive care unit with acute myocarditis, heart failure and severe arthritis. The diagnosis of Kawasaki disease was confirmed with echocardiographic evidence of coronary artery aneurysms and the development of the characteristic hand and foot desquamation. The patient's symptoms resolved with salicylates and intravenous gamma globulin therapy. He was discharged in good condition after 3 weeks of hospitalization. This is the first report of Kawasaki syndrome presenting with peritonsillar abscess. Although we discuss a unique presentation of this disease. Kawasaki syndrome often exhibits other otolaryngologic findings early in its course. A literature review of the clinical characteristics, pathogenesis and therapy of this disease is presented. PMID- 2262297 TI - A cephalometric and electromyographic investigation of patients treated for the correction of mandibular prognathism by mandibular surgery only. PMID- 2262298 TI - Jaw tracking in orthodontic diagnosis. PMID- 2262299 TI - Utilization of the Johnson Twin Wire appliance in an extraction case. PMID- 2262301 TI - Current concepts in hip joint replacement. AB - The authors present an overview of the 'state of the art' in hip joint replacement. Short and long-term success rates are discussed. PMID- 2262300 TI - The normal range of horizontal jaw position in an adult female sample. A comparison with Class II data. AB - Different variables for horizontal jaw position were calculated in an adult group of dental class I females. A large skeletal variation was found that was not significantly different from data based on class II samples. The null hypothesis for no difference between the various occlusion groups could only be rejected for those variables describing lower apical base relationship. The presence of a class II malocclusion may be due to an unfavourable dentoalveolar compensation rather than a basic deviation from the normal skeletal pattern. PMID- 2262302 TI - Orthopedist shortage continues. PMID- 2262303 TI - Cervical fractures in ankylosing spondylitis. AB - Cervical fractures in patients with ankylosing spondylitis (rheumatoid arthritis of the spine) are discussed. Early recognition is stressed. PMID- 2262304 TI - Bone graft craniofacial reconstruction. AB - Craniofacial reconstruction provides functional benefits such as allowing unimpeded brain growth in children or brain protection in adults like our patient. There are also significant psychological and social benefits. Before surgery, this patient refused to be seen in public because of his bizarre appearance; he now functions better. As William Mayo said, "It is the divine right of man to look human." PMID- 2262305 TI - Alcoholism and semi-truck drivers. PMID- 2262306 TI - Pre-meds: take acting? PMID- 2262307 TI - Long-term care residents and MI/MR/RC screenings. PMID- 2262308 TI - WIC's new rebate policy saves money. PMID- 2262309 TI - Analgesic use: a study of treatments used by patients for migraine prior to attending the City of London Migraine Clinic. AB - Eighty-three unselected patients attending the City of London Migraine Clinic for the first time were asked about their drug intake and use of alternative treatment. Thirty-one of those questioned took regular daily doses of medication. Fifteen were taking a combination of drugs bought 'over the counter' (OTC) and drugs prescribed by their GP; eleven took OTC drugs only; and 5 took prescription drugs only. It was noticeable that those taking drugs prescribed both by the GP and obtainable over the counter were more likely than the other groups to be taking several drugs rather than a single type. Thirty five of the 83 (42.2%) had tried alternative treatments for their attacks. PMID- 2262310 TI - Vasospasm contributes to monosodium glutamate-induced headache. AB - Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients. In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta. In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue). Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions. At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response. Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions. Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility. Only the central glutamate receptor antagonist, ketamine (10(-4) 10(-2)M), induced a reversible, concentration dependent inhibition of glutamate induced contractions. Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function. These results demonstrate a direct effect of glutamate on peripheral arterial tone. Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease. PMID- 2262311 TI - Alteration of platelet serotonin in patients with chronic tension-type headache during cold pressor test. AB - Change of 5-hydroxytryptamine (5-HT) concentrations in platelets from patients with chronic tension-type headache (TH) and controls were observed during cold pressor test (CPT). Before cold stimulation, 5-HT concentrations in platelets from patients with TH were significantly lower than those found in controls. One minute after the start of cold stimulation, 5-HT levels in platelets from patients with TH were significantly much lower than in the controls, as control levels rose and TH levels fell. The results show that, under stress, the absorbance of 5-HT into the platelets in patients with TH is reduced. It is suggested that, in patients with TH, there are abnormalities of 5-HT uptake into platelets and factors which cause release of 5-HT from platelets. PMID- 2262312 TI - The blink reflex in cluster headache. AB - To investigate the involvement of the trigeminal system in cluster headache, in twelve subjects the electrically-elicited blink reflex during a symptomatic period was examined. In eleven cases, the amplitude of the contralateral R2 response on the symptomatic side was significantly lower, at the same stimulus intensity, than on the asymptomatic side (p = 0.005). The blink reflex can be useful to evaluate biological and drug-induced phenomena in cluster headache. PMID- 2262313 TI - Assessment and treatment of children's headaches from a developmental perspective. AB - Childhood headache is a common pediatric problem. Clinical researchers have evaluated several behavioral treatment, such as biofeedback and relaxation training, that may be viable interventions. Adding a developmental perspective to the evaluation and treatment of childhood headache is a likely way to increase the effectiveness of these strategies. This paper presents developmental issues related to the assessment and treatment of childhood headache. Three major areas of development are examined and the impact of these areas on the treatment and assessment of headache are discussed. The three major areas are cognitive development, self-regulation and psychosocial development. Provided are practical suggestions for the application of child development principles to assessment and intervention practices that may be more developmentally appropriate. PMID- 2262314 TI - Health status in patients with tension headache treated with acupuncture or physiotherapy. AB - Sixty-two female patients with chronic tension headache were randomly divided into two treatment groups--acupuncture and physiotherapy. Their overall function (Sickness Impact Profile), and mental well-being (Mood Adjective Check List) and the intensity and frequency of headache were assessed before and after treatment. Before treatment the patients showed significantly more dysfunction and less positive mental well-being than a general population sample. Both treatment groups improved in overall function, the physiotherapy group somewhat more. The mental well-being increased only in the physiotherapy group. The intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group. The intensity of headache was significantly more improved in the physiotherapy group. The improvement of headache intensity persisted unchanged 7-12 months after treatment. PMID- 2262315 TI - Nocturnal sleep recording with cassette EEG in chronic headaches. AB - Many headache patients complain of poor sleep, and sleep disturbance has been shown to play a role in chronic pain. We recorded nocturnal sleep with a 4 channel cassette EEG monitoring device in 10 common migraine patients, 10 individuals with muscle contraction (tension) headache, and 10 chronic tension vascular headache sufferers. Migraine patients had essentially normal sleep, although rapid eye movement (REM) sleep and REM latency were increased. Patients with tension headache had reduced sleep time and sleep efficiency, decreased sleep latency but frequent awakenings, increased nocturnal movements, and marked reduction in slow wave sleep, without change in REM sleep or latency. Mixed element headaches with both tension and vascular features were associated with reduced sleep, increased awakening, diminished slow wave sleep, and REM sleep that was decreased in amount and reduced in latency. The findings suggest that patients with intermittent migraine may have minimal sleep disturbance, while chronic headache may be worsened by chronically poor sleep. Muscle contraction headache may be associated with frequent awakenings and decreased slow wave sleep similar to the sleep changes of fibrositis, while chronic tension-vascular headache may have a depressive substrate. Four-channel sleep recording may miss contributory sleep apnea, but nonetheless cassette EEG may facilitate outpatient evaluation of refractory headaches. PMID- 2262316 TI - Contingent Negative Variation in migraine. AB - The Contingent Negative Variation (CNV) is an event-related slow potential. It was recorded in healthy volunteers (n = 8) and in patients suffering from migraine without (n = 12) or with (n = 5) aura, during one (CNV1) and three second (CNV3) foreperiods in a forewarned reaction time task. CNV1 was recorded at the vertex while CNV3 was recorded at multiple electrode sites to assess topographical differences. Seven out of twelve migraine patients without aura had increased CNV1 amplitudes. CNV3 amplitudes were increased as well, but only at electrode positions C3 and C4 and not at Fz. CNV3, which allows for analysis of both an early and a late CNV component, could improve the discrimination of migraine without aura beyond that of CNV1. In migraine with aura all CNV parameters were at control levels, confirming previous results. The data obtained are discussed in terms of arousal, activation and stress and the "biobehavioral model of migraine" (Welch, 1986). PMID- 2262317 TI - Analgesic-induced headaches: an unrecognized epidemic. PMID- 2262318 TI - Back and to the future. PMID- 2262319 TI - Information-seeking about health in a community sample of adults: correlates and associations with other health-related practices. AB - Action by individuals to acquire information about their health has been an element incorporated throughout theory, research, and programs related to health promotion. This report describes an attempt to determine if an information seeking dimension could be empirically identified in a general community-resident sample, and if so, to examine some of its characteristics. A total of 281 adults aged 18-75 were contacted by telephone using random digit dialing and were interviewed about a variety of personal health practices. Factor analysis identified a five-item cluster representing a tendency to seek out information about health. Women were more likely than men to report seeking information. In addition, more frequent information-seeking was associated with favorable responses to several other health-related practices. Formal health service use was the only type of health practice not associated with information-seeking, perhaps because regularity of contact is influenced strongly by health professionals (e.g., reminder cards and having staff call to schedule annual exams). Overall, results of the investigation support the importance of information-seeking as a component of a personal health practice repertoire. Additional attention might be directed toward elaborating its role as a "process" variable in health education programs and social marketing efforts, particularly in areas such as response to recruitment messages, dropout vs. maintenance, and differential gains on outcome measures of program effectiveness. PMID- 2262320 TI - Predictors of employee involvement in a worksite health promotion program. AB - Although worksite health promotion programs have proliferated, little is known about the population they reach. This study of employees of a large utility company compared whether the same characteristics which predict recruitment also predict extended participation. The study also prospectively assessed how risk factors are related to employees' on-going extended participation. The findings demonstrate that sociodemographic predictors of recruitment are almost mirror images of the predictors of extended participation. Over time employees who are at higher risk for cardiovascular disease participated in on-going sessions less frequently. Data suggest that referral to targeted sessions does not result in higher rates of attendance by employees with a particular risk factor, although there is no evidence of selective avoidance. Organizational influences on participation evident from the beginning are sustained through four sessions. Programs targeting higher risk employees nested within worksite-wide programs may be useful to increase the extended participation of individuals at elevated risk for heart disease. PMID- 2262321 TI - Attributions for previous failures and subsequent outcomes in a weight reduction program. AB - This prospective study examines the effects of causal attributions given to previous weight control failures on subsequent success in controlling weight. Adult participants enrolled in a weight control program were screened to identify those who had made previous weight reduction attempts through a formal program. Once identified, subjects (n = 158) were asked to make causal attributions for their previous failures. Subjects were then followed through the 15-week program to determine their degree of success. Subjects who attributed the cause of previous failures to stable, immutable conditions were more likely to have low expectations of success. Low success expectancies, in turn, were associated with lack of goal attainment through the program. The number of previous failures in formal weight control programs was associated with a perception of the respondents that previous failures had stable causes. Neither the number of former failures nor the attributions of their causes were directly related to goal attainment. Practice implications of the results are discussed. PMID- 2262322 TI - Attendance at health promotion programs: baseline predictors and program outcomes. AB - As part of a family cardiovascular health promotion project, 111 Mexican-American and 95 Anglo-American families with fifth- or sixth-grade children were assigned to either a primary prevention program involving 18 sessions or to a control condition. This article evaluates predictors of attendance at the year long sequence of sessions in the intervention group. In addition it considers the relationship between attendance and program outcomes. Low baseline scores on physical activity and cardiovascular fitness measures were associated with higher attendance for both children and adults. High initial health knowledge and self motivation were also associated with attendance. Multiple regression analysis showed that adult attendance was significantly predicted by a model including completion of a three-day food record, low exercise, higher socioeconomic status, family adaptability, and self-motivation. Attendance was correlated with greater knowledge gains and larger reductions in blood pressure. The results indicate that motivated families who are in greater need of conditioning attended more sessions in a health promotion program. PMID- 2262323 TI - Increasing the use of mammography: a pilot program. AB - Despite the effectiveness of mammography, a large percentage of eligible women do not obtain screening mammograms. Two programs designed to increase the use of mammography were designed, implemented and evaluated. One hundred and fifty-six women were recruited and assigned to an Educational plus Psychological program (EP), an Educational program (E), or to a delayed treatment control group (C). Women completed a pretest, a posttest (EP and E only) and a telephone follow-up. At posttest, EP women had greater intention to obtain a mammogram than C women. EP and E women had higher levels of knowledge and higher levels of perceived benefit of mammography than C women. Actual compliance did not differ among the three conditions. Implications for the design of future programs are discussed. PMID- 2262324 TI - Health education for testicular cancer. AB - The incidence of testicular cancer is rapidly increasing. It is highly curable when detected and treated early, yet 500 to 1,000 men die from this cancer each year. Most victims are young men whose deaths account for a large number of potential years of life lost. Risk factors for testicular cancer are known but they cannot account for the increase in incidence. Only one age group, men between 15 and 34 years, is currently exhibiting an increase in incidence and mortality and should therefore comprise the primary at-risk group. Health education for the at-risk group, including promotion of regular and accurate testicular self-examination (TSE), could lead to earlier tumor detection and treatment and thereby save lives. PMID- 2262325 TI - Worksite follow-up and engagement strategies for initiating health risk behavior changes. AB - Information is presented from a multiplant study of interventions to improve cardiovascular health among employees. Risk factors targeted were high blood pressure, obesity, and cigarette smoking. The study utilized on-site wellness counselors who periodically contacted all employees identified through screening as having one or more of the three risks. Use of a structured protocol for client outreach resulted in the large majority of clients being seen in follow-up during the three-year intervention period. Drawing from caseload experience and from various theoretical perspectives, seven engagement strategies were used to help guide at-risk clients toward successful behavior changes to reduce health risks. Results showed that of the three at-risk groups, clients with high blood pressure were most likely to be seen in follow-up, and most likely to begin a risk reduction program. For the overweight and smokers, clients seen three or more times were more likely to begin a weight-loss/smoking cessation program than clients seen less often. Frequency of follow-up showed a positive relationship with risk reduction for all three risks, in samples of employees rescreened at the end of the intervention period, but the relationship was not statistically significant for smoking cessation. PMID- 2262326 TI - The Nellcor N-2500 MMGM. PMID- 2262327 TI - New ABS tables for the OEC-Diasonics 9000. PMID- 2262329 TI - Temperature probe jacks on Ohmeda infant radiant warmers. PMID- 2262328 TI - Heart-rate alarms on ZMI ZOLL PD 1200 pacemaker/defibrillators. PMID- 2262330 TI - Myosin, from the gene to the circulating forms. PMID- 2262331 TI - Interleukin 4. PMID- 2262332 TI - Melatonin in humans, neuroendocrinological and pharmacological aspects. PMID- 2262333 TI - Determination of circulating parathyroid hormone. PMID- 2262334 TI - TSH immunoassay: relationship between glycosylation & bioactivity. PMID- 2262335 TI - Comparison of merits of steroid radioimmunoassays using iodinated or tritiated radioligands. PMID- 2262336 TI - External quality assessment in clinical chemistry, review of the European situation with particular reference to hormonology. PMID- 2262337 TI - Regulations in Belgium for the "in vitro" use of radionuclides for radioanalyses. PMID- 2262338 TI - Immunology of insulin-dependent mellitus. PMID- 2262339 TI - Antinuclear antibodies: detection and diagnostic value. PMID- 2262340 TI - Metabolites of cyclosporine: blood and tissue levels. Biological activity? PMID- 2262341 TI - Clinical pharmacology of cyclosporine. PMID- 2262342 TI - Cyclosporin assay techniques. Accuracy and reproducibility variables impacting on measurements. PMID- 2262343 TI - French interlaboratory cyclosporine quality assessment scheme. PMID- 2262344 TI - Immunoelectron-microscopic localization of a proliferation-associated antigen Ki 67 in MCF-7 cells. AB - Immunocytochemistry using the monoclonal antibody Ki-67 is a commonly used method to assess proliferative activity of malignant tumours, Ki-67 reacts with proliferating cells with an antigen, whose structure, function and exact locations are unknown. We studied the subcellular location of Ki-67 in MCF-7 cells using immunoelectron microscopy. In the interphase cells, Ki-67 immunoreactivity was localized in the nucleolus, mainly in the nucleolar cortex. In particular, areas of the granular component of the nucleolus were strongly stained. Weak spot-like nucleoplasmic immunostaining was also seen outside the nucleolus. During prophase Ki-67 antigen was localized on the surfaces of the condensed chromatin and during metaphase on the surface of the chromosomes. After cell division and prior to formation of new nucleoli, Ki-67 immunoreactivity was located in the nucleoplasm. Quantification of Ki-67 immunofluorescence signal by flow cytometry revealed highest Ki-67 levels in mitotic cells. The location of Ki 67 is very similar to certain recently described proteins of nucleolar preribosomes suggesting that Ki-67 may also be a component of the preribosomes. PMID- 2262345 TI - Immunoelectron-microscopic studies of human platelet thrombospondin, von Willebrand factor, and fibrinogen redistribution during clot formation. AB - The relative distributions of the human platelet alpha-granule proteins fibrinogen, thrombospondin, and von Willebrand factor were mapped by immunoelectron microscopy in thin cryosections of activated platelets, platelet aggregates, and clots during the first 24 h of in vitro clot formation. In early activated platelets, the results suggest that the canalicular system constitutes a significant component of the external platelet surface, and may act as a compartment for biochemical reactions occurring during granule release. Further, detection of coagulation proteins by various non-morphological procedures may reflect protein contained within canalicular elements. Later in the release process, von Willebrand factor was detected as a major antigen on the platelet canalicular and plasma membranes; thrombospondin, on the other hand, showed minimal binding to platelets and only limited binding to the extensive fibrin network. Comparison of radioimmunoassays of supernatants of thrombin-stimulated platelets in plasma, clotted whole blood, and Triton X-100 platelet releasates indicated that virtually all of the platelet thrombospondin appears in serum. These data confirm the immunocytochemical results indicating that very little platelet thrombospondin binds to the platelet surface, compared with von Willebrand factor, studied here under the same conditions, which binds extensively to the platelet membrane following release and clot formation. PMID- 2262346 TI - [Current pathophysiologic aspects of allergic rhinitis. I]. AB - Allergic rhinitis is a classic example of a type I immunological reaction. After allergic provocation tests a biphasic reaction is seen in the respiratory tract that is more pronounced in the lower than in the upper respiratory tract due to the physiological changes during the nasal cycle. The early phase of the immediate reaction starts some minutes after allergen provocation. After 5-10 h the nasal symptoms (discharge, blockage, sneezing and itching of the nose) reappear, a phenomenon which is called the "late-phase response" (LPR). The LPR is of great clinical importance in the pathophysiology of perennial allergic rhinitis and phenomena such as nasal priming and nasal hyper-reactivity. The most important effector cell of the early phase of the immediate reaction is the mast cell, whereas basophils, eosinophils and neutrophil granulocytes seem to be more important for the LPR. There is also evidence for morphological and functional heterogeneity of mast cells in man. The role of the chemotactically immigrated eosinophils in allergic reactions has not been clear until now: the eosinophil derived mediators may enhance or inhibit the allergic reaction. Also the eosinophils show different morphological and functional states (so-called hypo- and hyperdense eosinophils). The symptoms of allergic rhinitis (sneezing, discharge, blockage, itching of the nose) are caused by different mediators, of which the most important is histamine. Other mediators or modulators of the allergic reactions are leucotrienes, prostaglandins, PAF, serotonin, and the kallikrein-kinine and complement systems. In recent years many regulatory peptides have been detected in the human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262347 TI - [Complications of endonasal surgery of the paranasal sinuses. Special anatomy, pathomechanisms, surgical management]. AB - Statistics show that there is no significant increase in complications in endonasal sinus surgery of the ethmoid or sphenoid as compared to paranasal or transantral procedures. Exact anatomical knowledge of the nasal cavity, the paranasal sinuses and related structures is essential for assessment and management in iatrogenic complications, which are divided in three groups, according to characteristic topographic implications: orbito-ocular, vascular, encephalomeningeal. Orbito-ocular complications are managed by decompression of the orbit using the paranasal approach. Direct lesions of the optic nerve in ethmoid- or sphenoid-sinus surgery are extremely rare and are due to an abnormal nervous course. Vascular complications in the branches of the external carotid artery require local procedures (e.g. transantral ligature of the sphenopalatine artery). In some cases an intra-arterial embolization using supra-selective angiography is more effective. Massive bleeding from lesions of the internal carotid artery is stopped by placement of a balloon catheter combined with a transfemoral intra-arterial digital subtraction technique. Iatrogenic dura defects in the frontal skull base can be managed easily once the lesion has been exactly and clearly localized. Adequate control of the frontobase including the orbit, optic nerve and related vascular and nervous structures is achieved by the extracranial subfrontal paranasal (Killian incision) approach, if endoscopic or endonasal microscopic repair is ineffective. PMID- 2262348 TI - [Audiologic diagnosis of tumor-induced neural hearing disorders based on discrete finding constellations]. AB - Modern electrophysiological and audiometric tests allow the cause of retrocochlear hearing loss to be diagnosed in almost all cases. Assessment of the stapedius reflex, discrimination using the Fowler test, the ERA findings with respect to inter-peak latency, interaural latency difference of the fifth wave, DORAS (difference between the objective response threshold and the subjective tone threshold), and finally the vestibular findings are all important. PMID- 2262349 TI - [Familial neural mitochondrial deafness]. AB - Mitochondrial abnormalities are known to cause several neurological syndromes that often include hearing loss as one of their features. We present two brothers with mitochondrial cytopathy and hearing loss. The audiological and electrocochleographic findings suggest a neural origin for the hearing impairment. Muscle biopsy is an important tool for the diagnosis of these syndromes in patients with audiological evidence of a bilateral neural hearing loss and neurological abnormalities. PMID- 2262350 TI - [Malignant hemangiopericytomas in the head and neck area]. AB - Since 1975 we have treated nine patients with a malignant haemangiopericytoma. Three patients died 5, 9 and 14 years later of metastasis in the lung, liver, skeletal system and mastoid. However, five of the patients are still alive. Regular clinical and radiological follow-up is performed, the average period of follow-up being 8.2 years. Four patients suffered local recurrence within 1-5 years. Surgical resection was the primary therapy in five cases, supplemented in two cases by local radiation. Recurrences were treated by surgery on four occasions and six by radiation, but no complete remission was achieved. Chemotherapy (CyVADic regimen) was attempted in three patients with metastases and one patient with a huge local recurrence, but proved to be ineffective. A re examination of the histological specimen of all primary tumours and recurrences did not reveal a correlation between histological appearance and clinical behaviour. Our experience in the treatment of malignant haemangiopericytoma and the data in the literature suggest that primary resection with a wide safety margin is the therapy of choice. Radiotherapy is recommended for incomplete resection, local recurrence, and metastases and inoperable tumours. Since recurrence and metastasis can occur after many years (up to 7 years in our patients) a lifelong regular follow-up is necessary. PMID- 2262351 TI - [Histopathology of the vestibular nerve in Meniere's disease]. AB - Histological and morphometrical investigations of the vestibular nerve were performed on surgical specimens from 19 patients suffering from Meniere's disease and on 5 autopsy preparations from patients without inner ear disease. The number of lipofuscin granules and vacuoles in the ganglion cells of specimens from Meniere patients was not increased compared with control specimens of a similar age, nor did the amount of endoneuronal connective tissue in the vestibular nerve specimens differ between the two groups. The density of capillaries in Scarpa's ganglion and vestibular nerve was significantly increased in the Meniere patients compared with the control specimens. Furthermore, the ratio of nerve fibres with a larger diameter was higher in specimens from Meniere patients than in control preparations. There was no difference in the density of myelinated fibres between the two groups. PMID- 2262352 TI - [Sialography with digital image processing screens]. AB - We recorded 45 sialograms on digital screens and discuss the use of a digital recording, processing and screening system for the diagnosis of inflammation, tumours and stones of the major salivary glands. Thirty-three investigations of a total of 33 parotid sialograms and 12 submandibular sialograms were analysed. A ductal examination with small volumes of soluble contrast media, permitting painless examination, was possible in all cases due to excellent homogeneous optical density, satisfactory detail and good contrast. PMID- 2262353 TI - [Cavernous hemangioma of the maxillary sinus]. AB - Cavernous haemangioma of the paranasal sinuses is very rare. We describe the X ray and CT findings in a case of cavernous haemangioma which originated from the mucous membrane of the maxillary sinus and eroded the bony boundary of the sinus. PMID- 2262354 TI - [Internal occlusive hydrocephalus following cholesteatoma]. AB - A 30-year-old Vietnamese patient is reported who was admitted with a resistant acute otitis externa, and who complained also of headache and fever. The symptoms were found to be caused by the intracranial complications (epidural abscess and bacterial meningitis) of an aural cholesteatoma. A secondary occlusive hydrocephalus developed in spite of successful otological surgery that preserved hearing and vestibular function. PMID- 2262355 TI - Concomitant boost radiotherapy schedules in the treatment of carcinoma of the oropharynx and nasopharynx. AB - Concomitant boost schedules are characterized by delivering the boost (10-12 fractions) as second daily treatments during rather than following the basic wide field irradiations. This results in shortening the overall time to administer 69 72 Gy from 7 1/2-8 weeks to 6 weeks, which we hoped would improve the tumor control rate by reducing the opportunity for tumor clonogens to regenerate during treatment. From August 1985 to August 1988, 79 patients with T2-4 carcinomas of the oropharynx (72 patients) or nasopharynx (7 patients) were treated according to 1 of the 3 variants of the concomitant boost technique. The median age of patients was 60 years (range: 19-84 years) and the male-to-female ratio was 2.6. The overall 2-year actuarial primary and nodal control rates by radiotherapy alone were 74% and 76%, respectively. The ultimate 2-year control rates after surgical salvage were 82% and 84%, respectively. If the boost given during the last 2-2 1/2 weeks of basic treatment, a slightly better primary control rate (p = 0.11) resulted than if the boost was delivered during the first 2-2 1/2 weeks or twice a week throughout the basic treatment. The 2-year actuarial primary control rate of the 13 patients receiving induction chemotherapy prior to radiotherapy was significantly lower than that of patients treated with radiation only (81% vs 34%, p = 0.01), but this could be partly attributed to a more advanced stage in the chemotherapy group. The acute mucosal reactions were, as expected, more severe than those observed with conventional fractionation. Fifty patients developed confluent mucositis covering more than half of the boost area. Such reactions lasted for more than 6 weeks in seven patients. Late complications, however, so far observed, have been few. Three patients experienced chronic mucosal tenderness, 1 chronic mucosal ulceration, 2 transient bone exposure, and 1 carotid rupture following salvage surgery. The results so far appear to be better than the outcome of conventional radiotherapy. Its real value will be determined in a prospective randomized study. PMID- 2262356 TI - Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. AB - From January 1978 to January 1988, 859 patients with T3-T4, NO-3, MO were randomly allocated to receive either: Group A--60Co 60, 60 Gy in 30 fractions; Group B--60Co, 70.4 Gy in 64 fractions; Group C--60Co, 60 Gy in 30 fractions plus chemotherapy (5 Fu, 250 mg/m2/IV every 2 days). Chemotherapy and radiotherapy were combined simultaneously. The average age was 56 years; the male/female ratio was 802/57. Median performance status (ECOG scale) was 1 (range 0-2). The TNM distribution as UICC criteria was T3 529 patients; T4 330 patients; No 217 patients; N1 52 patients; N2 319 patients; and N3 271 patients. The primary sites were nasopharynx 92, oral cavity 252, hypopharynx 119, larynx 310, and others (sinuses and unknown primary)86. Complete response was achieved in 188/277 patients in Group A (67.8%), 254/282 patients in Group B (90%), and 289/300 in Group C (96.3%). All patients were followed and statistical analysis shows a significant improvement in median duration of response, as well as survival for Groups B and C compared with Group A. No significant differences were seen between Group B and C. The acute toxicity was mucositis, skin toxicity, bone marrow depression. A mean temporary weight loss of 4.9 Kg was observed with a range of 2.3-10.5 Kg. PMID- 2262357 TI - Outcome analysis of localized gastrointestinal lymphoma treated with surgery and postoperative irradiation. AB - One hundred thirteen patients with localized gastrointestinal lymphoma treated by surgery and postoperative irradiation between 1967 and 1985 were reviewed. At 15 years, actuarial survival of this group was 40.6%, with a cause-specific survival of 69.2% and a relapse-free rate of 64%. Two-thirds of relapses occurred at distant sites. In Stage IA and IIA patients with no residuum or with positive resection margins, (N = 90) only site of involvement and stage predicted for relapse. Age, histologic subtype group, and depth of bowel wall invasion did not affect relapse risk. In the very favorable group (Stage IA, IIA, no residuum or microscopic residuum), 8.4% of patients with stomach lymphoma relapsed compared to 25% of patients with small bowel lymphoma. The risk of early relapse was higher in those with Stage IIA small bowel lymphoma than those with Stage IA small bowel lymphoma. We continue to recommend adjuvant abdominal irradiation for patients with Stage IA, IIA completely resected stomach lymphoma and Stage IA completely resected small bowel lymphoma. We recommend combined modality therapy for patients with completely resected Stage IIA small bowel lymphoma and all other localized gastrointestinal lymphoma where visible residual disease is present. PMID- 2262358 TI - Patterns of failure following curative resection of gastric carcinoma. AB - To identify patterns of failure following curative resection of gastric carcinoma, the records of 130 patients undergoing resection with curative intent at the Massachusetts General Hospital were reviewed. The total local-regional failure rate was 38% (49/130 patients), with 21 patients having local-regional failure alone and 28 patients having local-regional failure and distant metastases. The incidence of local failure rose with the more advanced stages of disease. Tumors staged B2, B3, C2, and C3 had local-regional failure rates in excess of 35%. This group of patients might benefit from adjuvant radiation therapy to the tumor bed and regional lymphatics. Local-regional failure rate was highest in the anastomosis or stump 33/130 (25%), followed by the stomach bed 27/130 (21%). The overall incidence of distant metastases was 52% (67/130 patients) and rose in the more advanced disease stages. Tumors staged B2, B3, C2, and C3 had rates of distant metastases greater than 50%. Sixty-one patients (77%) had failure in the abdomen (liver, peritoneal surface, adrenal, kidney, and spleen, but excluding tumor bed, anastomosis, or regional nodes). Patients with Stage B2, B3, C2, and C3 tumors had total abdominal failure rates greater than 40%. The highest failure rates in the liver were in Stages B3 and C3, in which the subsequent development of liver metastasis was 40% and 47%, respectively. Peritoneal seeding occurred in 30/130 (23%) of patients and was highest in Stages C2 and C3, with rates of 27% and 41%, respectively. PMID- 2262359 TI - Radiation therapy of squamous cell carcinoma of the nasal vestibule. AB - From 1978 until 1988, 63 consecutive patients with squamous cell carcinoma of the nasal vestibule were treated by radiation therapy. Mean follow-up time was 46 months. Thirty-five patients were classified as having T1N0 tumors, 24 as T2N0; four patients were staged as T1/2N+. Treatment of the primary consisted of external radiation (n = 17), interstitial radiation (n = 37), or external radiation combined with interstitial radiation (n = 9). With respect to the N0 patients, local relapse was found in 3% (1/35) of T1 tumors and in 21% (5/24) of T2 tumors. Three out of six failures were salvaged by surgery. Elective irradiation of both sides of the neck (40 Gy) was performed in 9 T1 and in 16 T2 patients. Two regional failures occurred in the electively irradiated necks, two in the non-irradiated necks. Regarding the T1/2N+ patients, three relapsed locally and/or regionally, and one remains NED. For all 63 patients, a 5-year corrected survival of 90%, a relapse-free survival of 80%, and an overall survival of 65% were observed. In summary, for optimal local control and cosmesis we feel that for T1,2 N0 tumor stages a dose of 60 Gy for T1 and 70 Gy for T2 tumors is adequate treatment. The primary tumor is irradiated preferentially in our view, by means of interstitial techniques; furthermore, our data do not support the use of elective neck RT. Although patients rarely present with lymph node metastasis (6%), the prognosis of T1,2 N+ patients remains grim and more aggressive (surgical) treatment might be needed for this category. PMID- 2262360 TI - Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue. AB - Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold. PMID- 2262361 TI - The effect of overall treatment time on local control in patients with adenocarcinoma of the prostate treated with radiation therapy. AB - Studies of patients treated with radiation therapy for squamous cell carcinoma of the head and neck have demonstrated that when all other variables are constant, protraction of the overall treatment time leads to a decreased probability of local control. Few data exist on the effect of overall treatment time on local control following irradiation of tumors that are generally thought to be slowly proliferating, such as adenocarcinoma of the prostate. This analysis was undertaken to determine the time-dose relationships for local control of prostatic adenocarcinoma at the University of Florida. All patients were treated at least 5 years prior to the date of analysis. For patients with Stage A2 disease, a tumor dose of 6500 cGy in 7 to 7.5 weeks to 7000 cGy in 8 weeks resulted in local control in 17/17 patients (100%). For patients with Stage B1 disease, the local control rate was 14/16 (88%) with an overall treatment time of less than or equal to 8 weeks versus 1/3 in patients who received split-course treatment in greater than 8 weeks (p = .097). For patients with Stage B2, C1, and C2 disease who received greater than or equal to 6500 cGy, the 5-year rate of local control was lower when overall treatment time was protracted beyond 8 weeks. Results were as follows: B2 (62 patients), less than or equal to 8 weeks, 88%, versus greater than 8 weeks, 55%, p = .002; C1 (87 patients), less than or equal to 8 weeks, 88%, versus greater than 8 weeks, 73%, p = .052; Cs (33 patients), less than or equal to 8 weeks, 81%, versus greater than 8 weeks, 65%, p = .056. Stratification by tumor grade of patients with Stage B1, B2, C1, and C2 disease who received greater than or equal to 6500 cGy demonstrated significantly lower local control rates for all grade categories when the overall treatment time was protracted beyond 8 weeks. Five-year local control rates (life-table method) for overall treatment time less than or equal to 8 weeks versus greater than 8 weeks were as follows: well differentiated, 93% versus 73% (p = .003); moderately differentiated, 86% versus 69% (p = .017); and poorly differentiated, 75% versus 59% (p = .046). These data suggest that tumor repopulation during excessively protracted treatment may be a clinically significant factor in patients with adenocarcinoma of the prostate. PMID- 2262362 TI - The role of serum prostatic acid phosphatase in the management of adenocarcinoma of the prostate with radiotherapy. AB - Between 1974 and 1983, 472 patients with clinically-staged adenocarcinoma of the prostate treated by radiotherapy had baseline and follow-up prostatic acid phosphatase (SPAP) measurements by the enzymatic Roy method. The mean pretreatment SPAP was higher in Stage C (0.65 mIU/ml) than in combined Stages A2/B (0.43 mIU/ml), (p less than 0.05). Likewise, the incidence of elevated SPAP (greater than 0.8 mIU/ml) was also higher in Stage C (12%) than in Stages A2/B (3%), (p less than 0.01). Only 3 of 113 patients in Stages A2/B had an elevated SPAP and all three remain disease-free. In Stage C elevated SPAP was an adverse prognostic factor, and patients with a normal SPAP fared worse if their value was in the upper half of normal (greater than 0.4 mIU/ml) rather than in the lower half (less than or equal to 0.4 mIU/ml). However, in Stage C, tumor grade was found to correlate with initial SPAP, so that the higher the grade, the higher was the mean SPAP and the greater was the incidence of elevated SPAP. When stratified for grade, the prognostic significance of low-normal versus high normal SPAP in Stage C was lost. An elevated SPAP was, however, an independent adverse prognostic factor for patients with intermediate and high grade tumors. Following radiotherapy, mean SPAP values fell significantly within 1-3 months. For patients with initially normal SPAP, this fall was of no prognostic significance. In 80% of the patients with baseline elevation of SPAP, the values normalized following treatment and the relapse rate in these patients was 51%, which was still higher than the relapse rate of patients with initially normal SPAP (33%) (p less than 0.05) but was lower than the 89% relapse rate in patients whose postradiation SPAP did not normalize (p less than 0.05). Pretreatment SPAP was of independent prognostic significance for only 6% of the study population and therefore has quite limited usefulness in the management of this disease. SPAP decreases following radiotherapy, but this is of prognostic significance only for the small group of patients with elevated pretreatment values. PMID- 2262363 TI - Hepatic function and drug pharmacokinetics after total body irradiation plus bone marrow transplant. AB - Radiation nephritis is the principle late toxicity seen after total body irradiation in barrier-maintained rats when hematologic toxicity is prevented by bone marrow transplantation. Renal dysfunction is observed for single doses as low as 7.5 Gy. Hepatic blood flow, as measured by indocyanine green clearance, is decreased after 8.5-9.5 Gy single-dose total body irradiation. Serum albumin levels are decreased after 9.5 Gy single-dose total body irradiation. Hypoalbuminemia is a symptom of hepatic damage, but can also be caused by renal damage or edema. No decrease in total serum protein is observed, indicating that proteinuria resulting from renal damage is not the cause of hypoalbuminemia. No edema and some dehydration are observed. These data indicate that hepatic damage as well as renal damage may be occurring after total body irradiation plus bone marrow transplantation. Animals given total body irradiation plus bone marrow transplantation show decreased tolerance to a wide variety of immunosuppressive and cytotoxic drugs, even when these drugs are given months after total body irradiation. Altered drug clearance after total body irradiation plus bone marrow transplantation is observed for cis-platinum, vincristine, and adriamycin. The increase in cis-platinum toxicity after total body irradiation plus bone marrow transplantation is caused by decreased renal drug clearance. The decrease in vincristine tolerance and the alterations in adriamycin and vincristine pharmacokinetics are caused by altered drug distribution after total body irradiation plus bone marrow transplantation. These results indicate that bone marrow transplant survivors may show altered clearance of, and decreased tolerance to, a wide variety of drugs that are used after bone marrow transplantation. PMID- 2262364 TI - Radioresponse of human astrocytic tumors across grade as a function of acute and chronic irradiation. AB - Astrocytomas make up the largest group of primary brain tumors of glial origin. Long term survival is rare with high grade tumors (grades 3 and 4), which recur despite subtotal resection, chemotherapy, and aggressive postoperative radiation therapy. In contrast, the 5-year survival for low grade astrocytomas (grades 1 and 2) following subtotal resection and postoperative radiotherapy approaches 50%. Variable sensitivity across grade may contribute to the difference in the behavior of these tumors. To investigate this possibility, the radioresponse of human glial tumors across grade as a function of the dose rate of irradiation was studied. Cell lines derived from a low grade astrocytoma (grade 1) and two high grade astrocytomas (grades 3 and 4) were established in culture. Clonal survival was determined following irradiation of the three cell lines with Cesium 137 gamma rays at high dose rate, 78 Gy/hr, and at low dose rate, range 14 cGy to 79 cGy/hr. The low grade astrocytoma was found to be more radiosensitive than either of the high grade tumors. The alpha/beta (Gy-1/Gy-2) values (linear quadratic model) were 0.35/0.082 for the grade 1 line and 0.20/0.036 and 0.30/0.045 for the grade 3 and 4, respectively. D0 (cGy) values (single-hit multi-target model) were 99, 144, and 117 for grades 1, 3, and 4, respectively. A dose rate effect was present for all three tumor lines irradiated from 14 cGy/hr to 78 Gy/hr. An inverse dose rate effect was also noted at 37 cGy/hr for each of the astrocytic lines. These findings may be useful in the development of strategies to treat astrocytic brain tumors which use high and/or low dose rate irradiation. PMID- 2262365 TI - Captopril reduces collagen and mast cell accumulation in irradiated rat lung. AB - The angiotensin converting enzyme inhibitor captopril ameliorates radiation induced pulmonary endothelial dysfunction in rats. The present study determined whether captopril also reduces collagen (hydroxyproline) accumulation in the lungs of rats sacrificed 2 months after a range of single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Captopril was administered in the feed at a regimen of 0, 25, or 50 mg/kg/day continuously after irradiation. Mast cell counts also were obtained from lungs of all animals exposed to 30 Gy. In rats receiving no captopril, there was a radiation dose-dependent increase in right lung hydroxyproline (HP) content and in HP concentration per g wet weight. Captopril produced a drug dose-dependent suppression in this radiation-induced HP accumulation. At a dose of 50 mg/kg/d, captopril reduced the slope of the radiation dose response curve for lung HP content by a factor of 1.7, and completely prevented the increase in HP concentration. At an isoeffect level of 550 micrograms HP per right superior lobe, this dose of captopril exhibited a DRF of 1.7 +/- 0.2. In rats exposed to 30 Gy, moreover, the number of mast cells per mm2 of alveolar cross-sectional surface area decreased from 105 +/- 8 to 100 +/- 7 and 59 +/- 5 in the groups given 0, 25 or 50 mg/kg/d of captopril, respectively, (vs none in sham-irradiated rats). These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis. PMID- 2262366 TI - Metoclopramide enhances the effect of ionizing radiation on xenografted squamous cell carcinoma of the head and neck. AB - The commonly used drug metoclopramide, a benzamide derivative, has been shown previously in our laboratory to enhance the effect of cisplatin on xenografted squamous cell carcinomas of the head and neck. In the present study, we show that metoclopramide also enhances the effect of ionizing radiation. Two human squamous cell carcinoma lines of the head and neck xenografted to nude mice have been used. Doses of radiation were chosen (5 and 8 Gy single doses) which caused only a slight retardation of tumor growth when administered alone. Tumor response to ionizing radiation was assessed with and without metoclopramide (2.0 mg kg-1), and administered at the time of radiation and 24 and 48 hr after treatment. The effects of these schedules on the tumors were compared using the reduction of the area under the growth curves and specific growth delay. The dose schedule with metoclopramide alone did not induce any significant reduction in the area under the growth curves. The addition of metoclopramide to the radiated groups caused a significant enhancement of the radiation-induced reduction of the area under the growth curves in both of the tumor lines studied. PMID- 2262367 TI - Delayed appearance of lethal and specific gene mutations in irradiated mammalian cells. AB - We have examined the occurrence of lethal and 6-thioguanine resistant (hprt locus) mutants among the progeny of irradiated CHO and BALB/3T3 cells. The expression of lethal mutations, as measured by a reduced cloning efficiency in the progeny cell population, was detected up to 30 mean population doublings after x-radiation. Preliminary evidence indicates that the expression of mutations at the hprt locus may also be delayed for at least 6-7 population doublings. These results suggest that radiation can induce genetic instability in cells, resulting in an increased rate of spontaneous mutations which persists for many generations of cell division. These findings are discussed in terms of their possible influence on the response of irradiated tumor cell populations in vivo. PMID- 2262368 TI - The interaction of cisplatin plus etoposide with radiation +/- hyperthermia. AB - The addition of concurrent etoposide and cisplatin to radiation +/- hyperthermia was evaluated in the murine FSaIIC fibrosarcoma tumor system. Tumor growth delay (TGD) demonstrated that when the drugs were tested with radiation (3 Gy daily X 5) plus (43 degrees X 30 min) local hyperthermia, cisplatin/hyperthermia/radiation (TGD approximately 25 days) was significantly more effective than etoposide/hyperthermia/radiation (TGD approximately 14 days). The addition of etoposide to cisplatin/hyperthermia/radiation, however, yielded a significantly longer growth delay (approximately 34 days). Tumor cell survival studies demonstrated that hyperthermia (43 degrees C, 30 minutes) was dose modifying for etoposide cytotoxicity (dose modifying factor approximately 2.0 as determined by comparisons of the slopes of the curves). The addition of etoposide to cisplatin modified cisplatin killing only slightly at 37 degrees C or 43 degrees C. Considerable additional cell kill was observed over a range of radiation doses with cisplatin, hyperthermia, and etoposide added singly or in combination, especially at the lowest radiation dose tested (5 Gy), but essentially no dose modification was observed. Evaluation of Hoechst 33342 dye selected tumor subpopulations demonstrated that cisplatin, etoposide, radiation (10 Gy), etoposide plus radiation, and cisplatin plus radiation killed significantly fewer dim (presumably hypoxic) cells than bright (presumably normally oxygenated) cells. Hyperthermia killed more dim than bright cells. The combination of hyperthermia with cisplatin and radiation, however, resulted in approximately 5-fold lesser kill in dim cells, and the addition of etoposide increased this differential to 6.4-fold. These results indicate that etoposide adds small but measurable antitumor effects when used with cisplatin alone or with cisplatin in combination with radiation +/- hyperthermia (especially at lower radiation fraction sizes). PMID- 2262369 TI - The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumors: an interim report. AB - The value of cell kinetic measurements in head and neck tumors in predicting which patients will benefit from accelerated fractionation radiotherapy regimens is being tested in a multicenter European trial (EORTC trial 22851). This paper reports on the first analysis of the correlation of kinetics with outcome in this trial. A proportion of patients in both the accelerated arm (72 Gy in 5 weeks, 1.6Gy per fraction, 45 fractions) and the conventional arm (70-72 Gy in 7-8 weeks, 1.8-2.0 Gy per fraction, 35-40 fractions) were given an i.v. injection of 100 mg/m2 IUdR (iododeoxyuridine) before treatment, and a tumor biopsy was taken several hours later. The potential doubling time of the tumor (Tpot) was obtained from a flow cytometric analysis of tumor cell nuclei using an anti-IUdR antibody. From a total of 260 patients entered in the trial, 53 have undergone kinetic analysis. Adequate IUdR labeling was seen in 47 patients (88.7%), from which the mean value for Tpot was found to be 4.5 +/- 2.5 days (+/- S.D.). Of the IUdR labeled patients, 30 have now been followed up for at least 1 year, 17 with conventional and 13 with accelerated radiotherapy. These patients were split into those with fast and those with slowly growing tumors, the dividing line being the median Tpot value of 4.6 days. After conventional 7-week radiotherapy, 2 of 6 patients with "fast" growing tumors obtained local control compared with 8 of 11 with "slow" growing tumors. A small difference in local control was seen been fast and slow tumors in the accelerated arm (5/9 vs. 3/4). These preliminary data support the hypothesis that patients with fast growing tumors do poorly with conventional radiotherapy and that pretreatment kinetic measurements can select patients at risk. The predictive power of the method must await the final analysis of trial results. PMID- 2262370 TI - Clinical patterns of failure following stereotactic interstitial irradiation for malignant gliomas. AB - The vast majority of patients treated for malignant gliomas with surgery, conventional radiation therapy, and systemic chemotherapy recur within 2 cm of their original disease site as documented by CT scanning. We have analyzed the clinical patterns of failure in patients treated with stereotactic interstitial irradiation (brachytherapy) for malignant gliomas in order to determine if this modality has altered the recurrence pattern in this disease. Between December 1985 and December 1989, 53 patients with malignant glioma were treated with stereotactic interstitial irradiation using temporary high activity iodine-125. Thirty-three patients were treated as part of a primary treatment protocol that included 5940 cGy external beam prior to implantation. Twenty patients were treated at time of recurrence. The median dose of radiation given at implantation was 5040 cGy for the primary lesions and 5450 cGy for the recurrent lesions. Twenty-two patients have suffered relapse as documented by clinical and radiographic studies. The predominant patterns of failure in these 22 patients were in the margins of the implant volume (8) and distant sites (10) within the CNS (distant ipsilateral or contralateral hemisphere, spinal axis) or extraneural. Thus, marginal and distant recurrences accounted for 82% of the relapses in our patients. We conclude stereotactic interstitial irradiation has changed the recurrence pattern in patients with malignant glioma with true local recurrence no longer being the predominant pattern of failure as is seen with conventional therapy. PMID- 2262371 TI - Two or six hyperthermia treatments as an adjunct to radiation therapy yield similar tumor responses: results of a randomized trial. AB - From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments. PMID- 2262373 TI - Influence of radiation on the blood-brain barrier and optimum time of chemotherapy. AB - A pilot study of the destructive effects of radiation on the blood-brain barrier (BBB) was made on 14 patients with localized and limited brain tumors by 99MTc-GH imaging from August 1988 to November 1989. Count/pixel data were obtained from the unirradiated, irradiated, and tumor areas before and after radiotherapy of 30 40 Gy. It was observed that, a) the BBB in the unirradiated area outside the radiation portal was not changed, b) the degree of destructive effect on the BBB in the irradiated normal area was directly proportional to the radiation dose. For 30-40 Gy, the count/pixel change enhances to average 24.7% [(147.6 118.4)/118.4], and c) the BBB in the tumor area is partially destroyed on an average of 22.1% [(206.8-169.4)/169.4] by the tumor. The radiotherapy further enhances this effect to an average of 74.7% [(206.8-118.4)/118.4]. Case 3 showed that before radiation, the degree of destructive effect on the BBB in the tumor area was 22% [(167-137)/137] higher than normal brain tissue. After a dose of 30 Gy of irradiation, it increased to 76.7% [(242-137)/137]; 8 months later it decreased to 17% [(160.3-137)/137]. It has been proven that the BBB can recover at least partially. Based on these observations, the authors believe that in the combined treatment of operated brain tumors, radiotherapy should precede chemotherapy so as to enhance the destruction of the BBB, facilitating the incorporation of drugs into the tumor. The dose at which to start chemotherapy is 20-30 Gy. PMID- 2262372 TI - Intracranial ependymomas in children. AB - Between 1970 and 1988, 51 children with intracranial ependymal tumors (33 infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors. PMID- 2262374 TI - Dose equivalence for high-dose-rate to low-dose-rate intracavitary irradiation in the treatment of cancer of the uterine cervix. AB - By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy. PMID- 2262375 TI - The effect of a dynamic wedge in the medial tangential field upon the contralateral breast dose. AB - The elevated incidence of breast cancer following irradiation of breast tissue has led to concern over the magnitude of the scattered radiation received by the uninvolved contralateral breast during radiation therapy for a primary breast lesion and the risk of an induced contralateral breast cancer. Some linear accelerators use a single dynamic (or universal) wedge that is mounted within the treatment head at an extended distance from the patient. Because of the combined effects of distance and shielding, the contralateral breast dose due to a medial tangent containing a dynamic wedge is expected to be less than that containing a conventional wedge. This paper presents contralateral breast dose (CBD) measurements performed on an anthropomorphic phantom with breast prostheses irradiated with 6 MV X rays from a linear accelerator equipped with a dynamic wedge. Doses were measured at 15 points within the contralateral breast prosthesis with thermoluminescent dosimeters. It was found that the contralateral breast dose per unit target breast dose decreases with the perpendicular distance from the posterior edge of the medial tangent to the dose measurement point and increases with effective wedge angle by factors ranging up to 2.8, in agreement with data presented earlier for a water phantom geometry. This dose elevation showed no statistically significant dependence (p less than 0.05) upon the perpendicular distance from the beam edge. Comparisons with data in the literature show that the contralateral breast dose increase by a dynamic wedge is typically only about half of that reported for a conventional wedge for the same wedge angle and distance from the beam. PMID- 2262376 TI - The use of a prosthetic tissue expander to displace bowel from a brachytherapy implant site. AB - We describe the use of a prosthetic maneuver to displace bowel from an implant site. The patient presented with a recurrent low grade fibrosarcoma which was grossly excised with positive microscopic margins in the right paravertebral area. For this reason we performed an Iridium-192 implant using afterloading catheters. Because of several dense adhesions, it was not possible to mobilize an omental sling over the implant site. To prevent the small bowel from lying on the catheters, we inserted a prosthetic breast tissue expander. This was expanded with saline and bacitracin solution and placed in the tumor bed overlying the catheters, thereby displacing the small bowel away from the sources. A postoperative CT scan with gastrograffin demonstrated that this procedure was effective. There were no complications. We conclude that such devices are suitable for use under these circumstances and can achieve the objective of decreasing the dose of radiation to the small bowel. PMID- 2262377 TI - Three-dimensional compensating filters using magnetic resonance images. AB - A technique for making radiation therapy compensators for missing tissue using magnetic resonance imaging (MRI) is presented. Magnetic resonance imaging was chosen for its ability to provide easily visible, accurate patient contours at any treatment angle. Phantom studies, including coronal cuts of a 45-degree phantom, showed that distortion in the magnetic resonance imaging is minimal, but that the image magnification should be checked by placing markers on the patient during the procedure. Water bath studies of 4 MV radiation dose uniformity in a compensated 45-degree phantom exhibited variations of less than 4% from the open beam profile. Errors in constructing and using compensators with this technique are analyzed and simulated. PMID- 2262378 TI - Improved dose homogeneity in the head and neck using computer controlled radiation therapy. AB - Computer-controlled radiation therapy techniques are demonstrated which improve dose homogeneity throughout the nasopharynx when compared to conventional treatment techniques. The typical approach using a heavily weighted anterior field and opposed wedged lateral fields results in a dose gradient from 95% to 110% or greater. All three of the computer-controlled techniques investigated improved the dose uniformity to a range from 95% to 105% or less. Multiple overlapping fields are used to compensate for patient anatomy and treatment beam characteristics. Treatment planning and monitor unit calculations are quite time consuming at this stage of development. Actual treatment time is not unreasonably long and can be improved in future releases of the therapy machine control software. PMID- 2262379 TI - Modeling of dose to tumor and normal tissue from intraperitoneal radioimmunotherapy with alpha and beta emitters. AB - Dose distributions for normal and tumor tissues from intraperitoneally administered radiolabeled antibodies have been calculated for 90-Yttrium (90Y), 131-Iodine (131I), and 211-Astatine (211At). The dose calculations use data on the activity of intraperitoneal fluid administered, the percent injected dose/gm uptake by tumor, biological half life, and a model for diffusion of antibody/radionuclide complex into peritoneal tissues. Calculations are performed for planar and hemispherical tumor shapes, ranging in size to establish the influence of geometry on dose distribution. Calculations for tumor geometry obtained from biopsies are also performed. When the activity is concentrated on or near the tumor surface, the maximum dose to a planar tumor for a 20 mci administration of 90Y is approximately 60 Gy, and falls rapidly to 50% of this value within 1 mm. However, for a hemispherical tumor, the dose is a maximum of 26 Gy, with an average of approximately 20 Gy. The surface dose from 131I (130 mci) is 240 Gy, and diminishes to 20 Gy in .05 cm in the planar case, whereas a hemispherical tumor receives a dose of 90 Gy over a large fraction of the volume, with the distal portions receiving 40 Gy. The surface dose for an administration of 70 mci of 211 At is 450 Gy and decreases to 50% of this value in 30 microns. Both surface geometry and tumor size are important determinants in the heterogeneity of tumor dose, as are the dose administered, antibody uptake, biodistribution, and residence time factors. These initial studies suggest that the size of disease which may be effectively treated is much less than the range of the particle emitted by radiolabeled antibodies. Furthermore, therapy is ultimately limited by the degree to which the antibody/radionuclide complex can diffuse and permeate the tumor. PMID- 2262380 TI - Treatment verification using a computer workstation. AB - The outcome of radiation therapy is clearly dependent upon the accuracy with which dose is delivered to the target volume. With the ever increasing use of oblique and even non-coplaner beams, verification issues have become more significant. Presently, radiation oncologists verify the accuracy with which treatments are delivered by comparing a reference ("prescription," usually simulator) on-film image to a portal on-film image on a lightbox. This process is fraught with difficulties as the images are usually rendered with different magnifications, orientations, and contrast. Using a computer workstation, a system has been created that allows a physician to enhance, register, and transparently overlay the portal image on the prescription image. As the prescription and portal images are rendered in shades-of-yellow and shades-of gray, respectively, a physician can interactively adjust the images and can easily detect set-up errors and/or beam placement errors. Thus greater treatment accuracy should be achievable, especially for unfamiliar beam orientations. PMID- 2262381 TI - Uncertainty in dose estimation for gynecological implants. AB - One source of uncertainty in doses computed for intracavitary gynecological applications is the imprecision inherent in localizing the sources and the points of interest on radiographs of the implant and in transferring that data into the treatment planning computer. To quantify the effect of these activities on the accuracy of computed doses, five physicists and two dosimetrists performed computerized dose calculations on five applications chosen randomly from our patient files. For each of these applications, doses were computed at the traditional points A and B and at points in the bladder and rectum. Using identical sets of films, each planner located both the radioactive sources and points of interest, or only the sources, or only the points of interest. Another set of films was used to measure the accuracy of digitizing alone. Planners received no instructions on either the definition or the placement of the points of interest. Overall uncertainties in computed doses to points A and B and bladder were found to be about 7%. Uncertainty in dose to the rectum was on the order of 50%. Analysis of the results showed that about 1% of the error was due to digitization and about 2% to identification of source locations. Among the individual planners, almost all of the dose variation was from differences in placement of the points of interest on the implant radiographs. The results demonstrate the need for standard definitions and locations for points of calculation so that meaningful comparisons can be made among institutions. PMID- 2262382 TI - Evaluation of time-dose and fractionation for 252Cf neutrons in preoperative bulky/barrel-cervix carcinoma radiotherapy. AB - Time-dose fractionation factors (TDF) were calculated for 252Cf (Cf) neutron therapy versus 137Cs for intracavitary use in the preoperative treatment of bulky/barrel-shaped Stage IB cervix cancers. The endpoint assessed was gross and microscopic tumor eradication from the hysterectomy specimen. We reviewed the data obtained in clinical trials between 1976-1987 at the University of Kentucky Medical Center. Preoperative photon therapy was approximately 45 Gy of whole pelvis irradiation in 5 weeks for both 137Cs and Cf treated patients. 137Cs implant was done after pelvic irradiation x1 to a mean dose of 2104 +/- 36 cGy at point A at a dose rate of 50.5 cGy/h. There were 37.5% positive specimens. Using Cf intracavitary implants, dose varied from 109 to 459 neutron cGy in 1-2 sessions. Specimens were more frequently cleared of tumor (up to 100% at appropriate dose) and showed a dose-response relationship, both by nominal dose and by TDF adjusted analysis of dose, dose-rate, number of sessions, and overall time. Limited understanding of relative biological effectiveness, schedule, effect of implants, and dose rate all made it difficult to use TDF to study neutron effects. Relative biological effectiveness (RBE) was estimated and showed that for Cf, RBE was a complex function of treatment variables. In the pilot clinical studies, a value of 6.0 had been assumed. The present findings of RBE for tumor destruction are larger than those assumed. Cf was effective for cervix tumor therapy and produced control without significant side effects due to the brachytherapy method used. The TDF model was of limited value in the present analysis and more information is still needed for RBE, dose-rate, and fractionation effects for Cf neutrons to develop a more sophisticated and relevant model. PMID- 2262383 TI - Individual variation and dose dependency in the progression rate of skin telangiectasia. AB - The progression rate of late skin telangiectasia after radiotherapy has been studied prospectively in patients for various fractionation schedules and dose levels. The degree of telangiectasia was scored on an arbitrary scale ranging from no detectable to totally confluent telangiectasia. Skin telangiectasia showed a progressive development at least up to 10 years. The rate of progression was strongly dose dependent. This finding has two important implications: the dose-latency relationship is steep, and the steepness of the dose-response relationship increases with the follow-up time. The most striking finding in this study was that the individual variation in progression rate was very large for the same treatment with a documented small variation in dose. For example, the latency for telangiectasia score 2 ranged between 17 and 90 months after 35 fractions of 1.8 Gy. The reasons for the large individual variation in progression rate are unclear and will be investigated further. PMID- 2262384 TI - Cancer epidemiology: implications for prevention and treatment. AB - Due to the results achieved in epidemiological research for the last 30 years, we are able to reduce considerably mortality from cancer through prevention and early diagnosis. The data required to accomplish these actions have been provided by epidemiology: (a) Descriptive epidemiology is the study of the frequency and the distribution of cancers, based on data concerning mortality and morbidity. These frequencies vary according to different parameters (i.e., sex, age, geographical situation). (b) Analytical epidemiology is able to pinpoint different risk factors (i.e., alcohol, tobacco, iatrogenic factors) through adequately conducted surveys. Primary prevention can attenuate the incidence of cancers by the suppression or reduction of certain risk factors. Secondary prevention permits the screening and treatment of precancerous lesions and avoids the secondary emergence of cancer (cervix uteri, colon). Early diagnosis is able to detect lesions at an early stage in their evolution where treatment is facilitated and where there are optimal chances of survival (breast). All of these measures for prevention and early diagnosis are being organized as large scale strategic campaigns (e.g., National Cancer Institute, European Communities). PMID- 2262385 TI - Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances. AB - Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultra-structural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. Either an increase or a decrease of BBB permeability, or both, occurring in a certain time sequence, was observed. The mechanism of hyperpermeability after irradiation is not fully understood, but the activation of vesicular transport offers one possible explanation. Even less understood is the mechanism of decreased permeability. The response of the BBB to ionizing radiation is most probably nonspecific and its nature may be assumed to be similar to its responses to other physical or chemical noxious factors. PMID- 2262386 TI - Non-standard CT scanners: their role in radiotherapy. AB - In the past 10 years a number of groups worldwide have investigated the extent to which the imaging requirements for radiotherapy planning may be met by the development of non-standard computed tomography (CT) scanners. Some of these groups have constructed apparatus based on a radiotherapy simulator gantry, others around a linac or a special purpose gantry. The performance of these systems is reviewed and the extent to which they have justified their promise has been assessed. The major use of simulator-based machines has been in planning radio-therapy in the thorax where tissue inhomogeneity corrections are important. Linac-based machines yield images useful for checking the positioning of patients at the time of therapy. Interest at the Royal Marsden Hospital culminated in the construction of a simulator-based CT system which achieved its present form in late 1985. The importance of the subsequent clinical study lies in our conclusive evidence that planning conservative radiotherapy for the breast without multiple level CT performed in the treatment position can have implications for local control of disease, pulmonary damage, and cosmesis. PMID- 2262387 TI - Gioacchino Failla. PMID- 2262388 TI - Will altered fraction schemes alter the future? PMID- 2262389 TI - O2 levels in normal tissues. PMID- 2262390 TI - Endobronchial irradiation: is HDR better? PMID- 2262391 TI - Oral contraceptives and serum lipids. PMID- 2262392 TI - Effect of stress and other biopsychosocial factors on primary antibody response. AB - There is growing evidence that life stress is associated with altered cellular immune function, but only a few studies have examined the effect of stress on humoral immune response. We immunized 89 healthy women (18-24 years) with a novel antigen, keyhole limpet hemocyanin (KLH), to study the impact of stressful events and psychosocial and biologic factors on primary antibody response to immunization. Antibodies to KLH were measured preimmunization and 3 and 8 weeks after immunization. Previously validated scales were used to measure (1) recent major stress (both "good" and "bad," as defined by the subjects) and minor stressful events, and (2) psychological status and social support. Subjects were also asked about personal medical history, sociodemographics, and side effects of immunization. Subjects with more stressful events (of any type) tended to have lower baseline and 3-week postimmunization IgG levels. Those reporting more "good" events tended to have higher IgG levels at 8 weeks postimmunization. Psychological Distress scores correlated negatively and Psychological Wellbeing scores correlated positively with each IgG level. Subjects with a recent infection (preimmunization) or a local reaction to immunization had significantly higher IgG levels at all three points compared to those without these factors. These data and exploratory analysis suggest that recent stress and psychological status (perhaps representing the cumulative effects of stress and response to stress) may influence immune response to immunization. However, predisposing biological factors must also be assessed for possible confounding in the stress immune response relationship. PMID- 2262393 TI - Preliminary results suggesting exaggerated ovarian androgen production early in the course of polycystic ovary syndrome. AB - Excess ovarian androgen production might be a cause of the polycystic ovary syndrome (PCO). Previous studies have evaluated adult women with long-standing abnormality of the hypothalamic-pituitary gonadal axis. Abnormal ovarian function in such patients could be a primary or even a secondary finding. For that reason, this study was designed to evaluate ovarian androgen production in symptomatic adolescent females. Simultaneous adrenal suppression, by using dexamethasone, and ovarian stimulation, by using gonadotropin-releasing hormone (GnRH), were achieved in 12 patients. Following stimulation, blood was serially obtained over 8 hr to measure gonadotropin, estrogen, and androgen responses. Based on the androgen response, patients could be divided into two groups. Group A (five) had a significant increase (p less than 0.01) in free testosterone, whereas group B (seven) had no increase in any androgen, including free testosterone (significantly different from group A, p = 0.01). All patients in group A had enlarged or cystic ovaries, whereas only one-quarter patients in group B had enlarged ovaries (significantly different from group A, p less than 0.03). The pituitary and estrogenic response was similar in both groups. These preliminary data suggest that some patients with PCO (group A) have a primary abnormality in ovarian androgen production early in the course of their disease. PMID- 2262394 TI - Tubal pregnancy in adolescence. AB - Fourteen women under age 19 were evaluated and treated for ectopic pregnancy at the Regional Medical Center, Memphis. These women were screened according to a protocol involving use of quantitative beta-human chorionic gonadotropin (beta hCG) and serum progesterone levels. All patients were in the first trimester of pregnancy, with a mean gestational age of 8.5 weeks based on menstrual dating. Ten patients denied knowing that they were pregnant prior to this evaluation. Because of the patients symptoms and clinical signs, nine patients underwent diagnostic laparoscopy at the time of initial evaluation. Of these, seven underwent either salpingectomy or salpingostomy for a ruptured ectopic pregnancy or ectopic greater than 3 cm in greatest dimension. Two patients were successfully treated without surgery. Five patients were discharged after their initial evaluation and were identified only by abnormal values on serial determinations of beta hCG and progesterone. One required salpingostomy, and the other four were successfully treated with methotrexate. Ectopic pregnancies identified at an early gestational age and prior to rupture are amenable to conservative treatment with methotrexate or laproscopic surgery. Patients who were identified by the protocol and not by clinical signs and symptoms were more likely to be candidates for conservative therapy. PMID- 2262395 TI - Contraceptive behavior among sexually active Hispanic adolescents. AB - The purpose of this study was to examine those factors associated with the contraceptive behavior of a national representative sample of Hispanic female adolescents. The subjects included all (n = 85) unmarried, sexually active Hispanic women, aged 15 to 19, from the 1982 National Survey of Family Growth. Contraceptive behavior was measured on a normalized scale, ranging from oral contraceptives to no contraception. Mexican/American and Central/South American background females were more likely (p less than 0.031) to use effective birth control than Puerto Rican, Cuban, and other Hispanic background subjects. Twenty additional social, behavioral, and demographic variables were found to be significantly associated (p less than 0.05) with contraceptive behavior. Based on multiple regression analysis, seven of these variables were found to explain 62% (p less than 0.0001) of the variation in the contraceptive behavior of this sample. Poorer contraceptive behavior was associated with noncompliance with the initial birth control method used (33.8%), lower coital frequency (8.3%), older postmenarchial age (5.7%), failure to use birth control at first coitus (4.6%), fewer years dating (4.0%), lower frequency of church attendance (3.3%), and never having experienced a pregnancy scare (2.0%). These findings suggest that the contraceptive behavior of Hispanic female adolescents is a dynamic process that can be understood in the context of previous sexual and contraceptive behavior. PMID- 2262396 TI - Assessment of pubertal maturity in boys, using height and grip strength. AB - A method is described for the convenient, noninvasive assessment of pubertal maturity in boys, which is intended for use in studies of developmentally related sports injury. Ninety-eight boys were evaluated for Tanner stage, age, height, weight, body mass index, and maximum (right or left hand) and average grip strength. Height and average grip strength were selected by discriminate analysis as independent predictors of maturity. Immature boys (Tanner stages 1-3) fell below average grip strength of 25 kg and were less than 65 inches (165 cm) in height, whereas boys who exceeded both of these measurements were mature (Tanner stage 4 or 5). This method was validated in a second sample of 99 boys with 100% specificity and sensitivities of 93.5% (immature boys) and 81% (mature boys). A subset of mature boys met the height criterion but did not achieve the average grip strength criterion for maturity. We propose the use of height and grip strength as a practical, noninvasive method to classify physical maturity in boys. In addition, we speculate that the subset of boys who are tall, but weak, may be at increased risk for certain types of sports injuries. PMID- 2262397 TI - Depression, self-esteem, and life events in adolescents with chronic diseases. AB - This study assesses whether nonhospitalized adolescents with chronic diseases differ from their healthy peers on standardized measurements of depression, self esteem, and life events. The study group consisted of 80 patients (20 with sickle cell disease, 40 with asthma, and 20 with diabetes). All patients had been admitted at least twice in the preceding year, had their disease for at least 2 years, and were between the ages of 12 and 18. The control group consisted of 100 adolescents, matched for age and socioeconomic status, from local schools. All subjects completed a questionnaire compiled from the Beck Depression Inventory (BDI), the Rosenberg Scale of Self-Esteem, and the McCutcheon Life Events Checklist. Adolescents with chronic disease had higher depression scores (p less than 0.001) and lower self-esteem (p less than 0.001) than their healthy age matched controls. There was no statistically significant difference in life events between the chronic disease and control groups. Depression, self-esteem, and life events did not differ significantly among the three disease groups. These findings suggest a need for intervention strategies to address depression and low self-esteem in adolescents with chronic disease. PMID- 2262398 TI - Rehospitalization of infants born to adolescent mothers. AB - This study defines the variables that predict rehospitalization of infants born to teen mothers. Rehospitalization was defined as hospital admission during the first year of life subsequent to hospitalization at birth. Normal birth weight (NBW), but not low birth weight (LBW), infants of adolescent mothers had higher rehospitalization rates than infants of older mothers. NBW infants of young vs. older mothers had significantly higher rehospitalization rates for gastroenteritis. Among infants of adolescent mothers, the variables associated with increased risk of rehospitalization were unemployed household head, presence of a congenital anomaly or developmental delay, and an unusually high or low number of well child care visits. Although individual variables were significant at the bivariate level, in combination, these variables were poor predictors of which infants would be rehospitalized. Our study suggests that all teen mothers of NBW infants may require additional education to prevent excess rehospitalization of their infants. PMID- 2262399 TI - The role of MRI in evaluation of an adolescent with a pelvic mass. AB - Abnormalities of the genital tract are common in adolescent females. Evaluation of pelvic pathology generally involves the use of ultrasonography. Recently, MRI has been shown to be effective in the diagnosis of pelvic pathology in adult females. Here, we present the case of an 11-year-old female with a pelvic mass in whom MRI proved to be an important diagnostic tool. PMID- 2262400 TI - Effect of ovariectomy and ovariectomy with ovarian autotransplantation on feedlot performance and carcass characteristics of heifers. AB - Feedlot growth performance and carcass characteristics were examined in 96 crossbred heifers of continental breeding. Heifers were assigned to four treatment groups: intact control, sham ovariectomized, ovariectomized, and ovarian autografted. Ovarian autografted heifers were bilaterally ovariectomized via a left flank incision and one ovary was bisected sagittally and implanted in the musculature of the flank. Animals were fed a diet based on corn silage and were slaughtered at a weight of about 450 kg. There was no effect of treatment on feedlot performance or objectively measured carcass traits. However, carcasses of ovariectomized and ovarian autografted heifers had lower maturity scores than carcasses of the intact and sham-ovariectomy heifers. Blood samples were collected monthly throughout the study. Progesterone concentrations in these samples indicated that approximately 20% of the ovarian autografted heifers exhibited ovarian cyclicity. Examination of the transplanted ovaries at slaughter indicated that approximately 20% of the transplanted ovaries were resorbed. Cavitated, fluid-filled, thick-walled structures that were considered to be luteinized follicles were the most prominent structures found on the transplanted ovary; these were found in one-third of the ovarian autografted heifers. These results indicate that an ovary transplanted to the musculature can remain viable; however, its physiological function is disrupted and it does not affect rate or efficiency of gain or carcass composition compared to ovariectomized heifers. PMID- 2262401 TI - Influence of dietary protein concentrations on performance and nitrogen repletion in stressed calves. AB - Three trials were conducted to determine the influence of dietary CP concentration on health and performance of market-transport-stressed feeder calves (Exp. 1 and 2) and on repletion of nutrients lost during a 3-d feed and water deprivation period in steers fed at maintenance energy intake (Exp. 3). In Exp. 1 (84 calves) and 2 (256 calves), feeder calves averaging 184 kg were transported from Tennessee to Texas. In Exp. 1, calves were fed receiving diets containing either 12 or 16% CP. In Exp. 2, calves were fed diets containing 12 or 16% CP and .8 or 1.3% potassium in a 2 x 2 factorial arrangement of treatments. In Exp. 3, four Hereford steers averaging 253 kg were used in an N balance trial. Steers were deprived of feed and water for 3 d and then were limit-fed (1 x maintenance energy requirements) diets calculated to meet 100, 120, 140 or 160% of CP maintenance requirements for 14 d in a 4 x 4 Latin square design. In Exp. 1, calves fed the 16% CP diet had faster (P less than .05) daily gains and higher (P less than .10) feed consumption than calves fed the 12% CP diet during the first 14 d. In Exp. 2, calf performance was not affected by diet CP or K content. Calves fed the 16CP-1.3K diet had lower (P less than .10) mortality than calves on the remaining treatments. In Exp. 3, N balance and serum urea N increased linearly (P less than .05) with increasing dietary CP. Results of these studies are interpreted to indicate that the CP requirement (g/d) of market-transport stressed feeder calves is similar to requirements of nonstressed calves; however, the CP concentration of the diet of stressed calves may need to be increased when feed intakes are low. PMID- 2262402 TI - Feeding frequency and the addition of sugar to the diet for the lactating sow. NCR-89 Committee on Confinement Management of Swine. AB - Effects of feeding frequency and addition of sugar to the diet for the lactating sow were investigated using 162 sows (10 replications) at four stations in the North Central Region. Sows were assigned to one of four treatments immediately after parturition (d 0). The four treatments were a corn-soybean meal diet (control) vs a similar diet containing 2.5% feed grade sucrose (sugar) and once vs thrice daily feeding. No feeding frequency x diet interactions (P greater than .10) were observed for any of the response criteria. Feed consumption and weight loss during lactation were not affected (P greater than .10) by treatments. Also, treatments had no effect (P greater than .10) on numbers of live pigs at parturition, pig survival or litter weight at d 21. The percentage of sows in estrus within 30 d after weaning was not affected (P greater than .10) by treatment. Of those sows that expressed estrus within 30 d postpartum, the weaning-to-estrus interval of sows fed sugar was 1.3 d shorter (P less than .05) than for sows fed the control diet. Neither feeding frequency nor addition of sugar to the diet affected feed consumption or reproductive performance of the sow during lactation. Because feed consumption and weight loss of the sow were not affected by diet, no reason for the slight reduction in the weaning-to-estrus interval of sows fed sugar is evident. PMID- 2262403 TI - Using live animal ultrasound measures of ribeye area and fat thickness in yearling Hereford bulls. AB - Ultrasonic measurements of fat thickness (FAT) and ribeye area (REA) were analyzed together with weight (WT), scrotal circumference (SC) and age data from 385 yearling Hereford bulls representing 45 sires. Additional variables created were 100*REA/WT (REACWT) and 365-d adjusted REA (AREA). Multiplicative age adjustment for AREA was calculated from linear regression of REA on age. Heritabilities were .45 +/- .17 for REACWT, .36 +/- .16 for WT, .12 +/- .13 for REA, .11 +/- .13 for AREA, .04 +/- .13 for FAT and .18 +/- .14 for SC. Phenotypic and genetic correlations were strongly negative for WT with REACWT. Neither AREA nor REACWT alone were considered suitable muscling variables due to their association with age, WT and FAT. Ultrasound REA measurements should be adjusted for the linear effects of age and WT and quadratic effects of FAT before being used for selection. Measurement of SC indicated a strong association with WT (r = .55) and a moderate positive genetic correlation with REA (.49 +/- .58). PMID- 2262404 TI - Multivariate genetic evaluation in swine combining data from different testing schemes. AB - A computational strategy is presented that allows rapid implementation of genetic evaluations using multivariate mixed models. Data generated in different testing programs such as field tests of boars and gilts, litter recording schemes and station tests of sibs may be combined to provide an estimate of the aggregate genotype. Residual and additive genetic covariance structures are given for the multivariate evaluation of individual measurements and group averages because they often are collected for sib groups at test stations using a modified animal model. Pseudo code is given for the implementation of a "generic" testing structure illustrated by a numerical example based on six traits from field tests of boars and four traits from station tests of sibs. BLUPs for all six traits are calculated for boars, parents and sib groups. Aggregate genotypes that correspond to the selection indices commonly used are calculated for selection candidates. PMID- 2262405 TI - Genetic and environmental trends in German swine herdbook populations. AB - Environmental and genetic trends for swine herdbook populations for Germany for the years 1979 to 1987 were estimated using mixed model methodology on test station data. Daily gain (DG), feed conversion efficiency (FCE), lean-to-fat ratio (R) and meat quality (Goefo) were analyzed simultaneously with different incidence matrices. Breed, season and test station were fixed effects; herd, litter and additive genetic effects for sib groups were random effects. Because the relationship data were incomplete, unknown ancestors were assigned to genetic groups. Carcass weight was included as a covariable for R. In DG, FCE and R, season was defined as month of test over all breeds and test stations. On the other hand, season for Goefo was replaced by slaughter location-date interaction. Cumulative genetic responses from the multivariate analysis for the component traits of the aggregate genotype ranged from 22 g to 55 g in DG, -.7 to 3.2 units in Goefo, -.1 to .5 in valuable cuts, and -.04 to -.15 in FCE. Cumulative monetary response over these 9 yr. per pig were $4.3, $3.7, $6.2 and $5.1 for German Landrace, German Large White, Pietrain and German Landrace B. Important environmental trends were found in FCE, Goefo and R. Total genetic improvement amounted to 1.6% of the value of national pork production in Germany during these 9 yr. With incomplete convergence, the genetic response was underestimated and environmental trends were overestimated. PMID- 2262406 TI - Alternative methods of selection for litter size in mice: I. Characterization of base population and development of methods. AB - Studies on a base population of mice were used to establish an index of components of litter size and a physiological model for measuring uterine capacity to be used subsequently in a selection experiment evaluating alternative methods for practicing selection to increase litter size. Heritability estimates of litter size, ovulation rate and ova success (fraction of ova resulting in fully formed pups) were .18, .33 and .15, respectively. No significant genetic or phenotypic correlation was found between overall ovulation rate and ova success. Phenotypic means and genetic variances were higher for characteristics measured on the right than on the left side of the reproductive tract. Linear and quadratic selection indexes, derived for a quadratic definition of breeding value, were compared. The linear index was predicted to be .99 as efficient as the quadratic one. Due to simplicity, the linear index (I = 1.21 x ovulation rate + 9.05 x ova success), scaled to have variance the same as litter size, was chosen for use. Ovulation rate in unilaterally ovariectomized females was .95 of that in females with both ovaries. No hypertrophy of the ipsilateral uterine horn in unilaterally ovariectomized females was found before implantation of embryos. Thus, unilateral ovariectomy appears to provide a physiological state to measure uterine capacity (as litter size) in the mouse. PMID- 2262407 TI - Alternative methods of selection for litter size in mice: II. Response to thirteen generations of selection. AB - Selection was conducted on an index of components of litter size (I = 1.21 x ovulation rate + 9.05 x ova success; ovulation rate measured by number of corpora lutea and ova success measured as number of pups born + number of corpora lutea), on uterine capacity (measured as number of pups born to unilaterally ovariectomized dams) and on litter size concurrent with an unselected control for 13 generations. Selection criteria (IX = index, UT = uterine capacity, LS = litter size and LC = control) were applied in each of three replicates. In an evaluation after five generations, IX and LS each exceeded LC by about .5 pups, with no response in UT. After 13 generations, mean ovulation rate, ova success and litter size (measured as number of fetuses at 17 d gestation in intact females) were, for IX, 14.25, .84, 11.95; for LS, 14.15, .82, 11.64; for UT, 12.61, .86, 10.77; and for LC, 12.27, .82, 9.98. The regression of number born (litter size in IX, LS and LC; uterine capacity with only a functional left uterine horn in UT) on cumulative selection differential across 13 generations was .12 +/- .01, .09 +/- .02 and .08 +/- .02 for IX, LS and UT, respectively. The regression of breeding value for litter size on each selection criterion, estimated as response in the generation-13 evaluation divided by cumulative selection differential, was .11 +/- .02, .08 +/- .01 and .05 +/- .03 for IX, LS and UT, respectively. Regression of response in number born on generation number was .17 +/- .01, .15 +/- .04 and .10 +/- .02 for IX, LS and UT, respectively. Selection in IX was promising relative to LS, and selection in UT changed number born. PMID- 2262408 TI - Correlated responses in body composition based on selection for different indicator traits in mice. AB - Correlated responses in whole-body composition were determined in 12-wk-old male mice from replicate lines selected for 12 generations for high (HF) or low (LF) epididymal fat pad weight as a percentage of body weight (EPID) and high (HL) or low (LL) hind carcass weight as a percentage of body weight. The HF and LF lines diverged (P less than .01) in body fat percentage (FAT) and subcutaneous depot fat by 93 and 71%, respectively, of the control line (RC) mean. EPID increased (P less than .01) proportionately more than FAT in the HF line; EPID decreased (P less than .01) proportionately less than FAT in LF. Protein, fat and water as a percentage of empty body weight showed negative correlated responses (P less than .01) due to selection for EPID, but lean body mass, body weight and body length had positive correlated responses (P less than .01). Correlated responses of fat free protein and ash percentage were minor. Correlated responses in HL and LL were the mirror images of those in HF and LF, but they generally were of smaller magnitude. The results indicate that, although there are high positive genetic correlations between fat depots in mice, local control of lipogenesis and(or) lipolysis exists at different sites of fat deposition. Further, the lack of correlated responses in fat-free percentage of protein (and percentage of ash) suggests that additive genetic variances are low for these traits and(or) the genetic correlations of these traits with the selection criteria are low. PMID- 2262409 TI - Sources of maternal odors and the development of odor preferences in baby pigs. AB - Seven experiments utilizing 77 litters of piglets were conducted to determine the relative preferences or aversion of piglets for maternal olfactory cues. A Y-maze was used to test piglet preferences for two substances at any one time. A preference index was calculated from Y-maze data to identify whether piglets expressed a preference or aversion to the two substances tested in each session. The first two experiments examined piglet preferences for maternal fecal odors, colostrum, milk, urine and skin washings at 12 h and 7 d of age. Piglets preferred the odor of nipple washings and sow feces at 12 h of age. Piglets preferred sow fecal odors at 7 d of age in one study. The third study showed that piglets could discriminate between their mother's fecal odor and fecal odors from other sows. The fourth study examined piglet preferences for maternal fecal odors at birth, 12 h and 1, 3 and 7 d of age. At all ages tested except birth, piglets preferred sow fecal odors over water. The final three studies showed that piglets did not prefer to be near novel odors (orange and banana odors), nor did they prefer to be near the putative rat maternal pheromone, deoxycholic acid. In conclusion, piglets learn their mother's odor within the first 12 h of life. Piglets are most attracted to the odors associated with maternal feces and skin secretions. Piglet odor discriminatory ability is specific for maternal odors (not just odorous substances) and very acute (they can discriminate between mother and non-mother odors). When modifying piglet behavior to improve survival, the piglet's well-developed olfactory ability should be considered. PMID- 2262410 TI - Short-term individual housing temporarily reduces the libido of bulls. AB - The objective of the present study was to determine the effects of short-term (6 wk) individual housing on the sexual interest (libido) of sexually experienced bulls. Twenty-two Hereford bulls reared with both males and females (BMF) or in all-male groups (BM) and approximately 21 mo of age were given free access for 40 min to five restrained females in hormonally-induced estrus and restricted access for 30 min to a single enclosed estrous female on two separate occasions. Free access tests were administered to bulls in groups of five or six individuals, whereas bulls were tested individually in restricted-access tests. After testing, half the animals were housed individually (physically isolated from conspecifics) and half remained in group housing for a 6-wk period. Libido tests were administered again at the end of the treatment period and 2 wk after reinstatement of group housing for the experimental subjects. Individually housed bulls exhibited fewer mounts (P less than .001) and spent less time with females (P less than .01) in tests administered during physical isolation than before or after treatment. Individual housing did not affect BMF and BM bulls differentially. In conclusion, short-term individual housing temporarily reduced libido of beef bulls. PMID- 2262411 TI - Comparison of bite size, biting rate and grazing time of beef heifers from herds distinguished by mature size and rate of maturity. AB - Sixteen-month-old heifers from herds having known genetic growth patterns were compared for differences in grazing behavior in a 3-yr study. Treatments were heifers from four size-maturity groups defined by the mature size and maturing rate of cow herds in which they originated. Average growth curve parameters indicating mature BW and rate of maturing in these cow herds were 387 kg and .19%/d for treatment Group I; 413 kg and .18%/d for Group II; 468 kg and .15%/d for Group III; and 589 kg and .16%/d for treatment Group IV. Data were from three heifers per treatment group grazing Midland bermudagrass during June and July observation periods. With the exception of the Group II vs Group III comparison, bite size increased with current or mature BW. Biting rate values were similar for all treatment groups but lower than those previously reported on other grass swards. Grazing time increased (P less than .01) in treatment groups defined by larger mature BW. Differences in grazing time for Group IV vs the other treatments and Group I vs Group II and Group III were observed repeatedly; the Group II vs Group III comparison was significant in one period during each of the 3 yr. Diurnal variations in grazing patterns among the treatments were observed. Period of observation affected (P less than .001) bite size and grazing time. These effects were not associated with month but could best be explained by differences in forage height and total mass. Forage availability had a direct influence on bite size, and a compensating effect of longer grazing time with smaller bite size was demonstrated as a regulator of intake. Differences in ingestive behavior were associated with genetic growth patterns in cattle. PMID- 2262412 TI - Stimulation by colostrum or mature milk of gastrointestinal tissue development in newborn pigs. AB - Porcine colostrum and milk were orally administered to newborn pigs to evaluate their gastrointestinal growth-promoting activity. Five piglets per treatment group were gavage-fed 5% lactose (L), defatted colostrum (C) or defatted mature milk (d 16 of lactation) (M) at 3-h intervals over a 24-h period. Colostrum and milk were administered on equivalent dry matter basis and all piglets received 1 mCi of [3H]thymidine per kg BW at the onset of feeding. Small intestines of C- and M-fed pigs were 1.6-and 1.3-fold, respectively, the weight of small intestines of those fed L (P less than .01). Total DNA content of intact small intestines were not different among groups; however, cpm [3H]thymidine/mg intestinal DNA of C and M piglets exceeded (P less than .05) that for L piglets. DNA content and cpm [3H]thymidine of intestinal mucosa did not differ among groups. Total protein in the intestines and intestinal mucosa of C pigs exceeded (P less than .01) that for L and M pigs. Total RNA in the small intestine and intestinal mucosa were similar for C and M groups but less (P less than .01) for L piglets. Stomach and pancreas weights among all pigs were similar, although C and M pigs exceeded L pigs in stomach (P less than .01) and pancreas (P less than .01) RNA content. In contrast, no differences in stomach DNA, protein and cpm [3H]thymidine or in pancreatic DNA, protein and cpm [3H]thymidine were detected. SDS-polyacrylamide gel electrophoresis was used to identify qualitative and quantitative differences in the protein compositions of porcine colostrum and mature milk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262413 TI - Morphometric analysis of involuting bovine mammary tissue after 21 or 42 days on non-suckling. AB - Mammary gland involution was morphologically evaluated 21 or 42 d after prevention of suckling of one udder half in 10 crossbred beef cows. Parenchymal tissue was taken from lower, middle and upper zones of each quarter from the teat to the ventral body wall. Udder halves, trimmed of extraparenchymal tissue, were weighed and used for DNA determination. DNA content was reduced 50 and 64% after 21 and 42 d of involution. However, the percentage of tissue occupied by epithelium was similar in suckled and nonsuckled glands. Well-differentiated cells, typical of suckled glands, were rarely observed in nonsuckled glands. Alveolar structure was evident in nonsuckled glands, but the number of cells per alveolar cross-section was reduced (30 vs 22). Unlike in suckled glands, there was a marked gradation in classification of epithelial cells across zones in involuting glands. For example, nearly 10% of the epithelium was well differentiated in the tissue from the upper zone, whereas no well-differentiated cells were found in the lower zones. Regression of the mammary parenchyma does not occur uniformly through the udder, so use of single biopsy to study involution should be avoided. Presence of alveoli after 42 d indicates that redevelopment of the udder with subsequent lactations is less dramatic than suggested from study of other species. PMID- 2262414 TI - Adipose tissue cellularity and muscle growth in young steers fed the beta adrenergic agonist clenbuterol for 50 days and after 78 days of withdrawal. AB - Angus steers (n = 40; approximate weight = 300 kg) were administered the beta adrenergic agonist clenbuterol for 50 d (7 mg.hd-1.d-1), followed by a 78-d withdrawal period. Carcass fatness variables did not differ (P greater than .05) between treated and control animals either after 50 d or after 128 d. Weights of the 9-10-11th rib longissimus muscle were 25% larger, and longissimus cross sectional areas were 28% greater, in clenbuterol-fed steers relative to controls from 0 to 50 d (P less than .05). After withdrawal these measurements increased no further in the treated steers. Marbling scores were decreased (P less than .05) in clenbuterol-fed steers after 50 d of treatment; this effect persisted after 128 d of withdrawal from treatment. Shear force values were increased 19% (P less than .05) by feeding clenbuterol for 50 d and remained greater (P less than .05) in treated animals after 128 d. Subcutaneous adipocytes in clenbuterol fed steers were smaller (P less than .05) than those of controls after 50 d, and this effect was still apparent after the 78-d withdrawal period. Rates of lipogenesis did not differ (P less than .05) between treated and control animals at any time. Perirenal (p.r.) adipocytes were smaller (P less than .05) in treated animals after 50 d, but this effect disappeared by the end of the experiment. There was no indication of a bimodal distribution of smaller s.c. or p.r. adipocytes in either of the treatment groups. Apparent hyperplasia of s.c. adipocytes occurred in the area of the 9-10-11th rib in both treated (P less than .10) and control animals (P less than .05) from 0 to 50 d on trial. Within treated animals there was a significant increase (P less than .05) in total adipocytes in this depot during the withdrawal period. Although the effects of clenbuterol on muscle growth generally were reversed after 78 d, the effects of the beta-adrenergic agonist on adipose tissue development were more permanent. PMID- 2262415 TI - Antimicrobial supplementation of growing pigs: the effect of porcine sera fractions on in vitro muscle cell proliferation. AB - Sera obtained from pigs before and after subtherapeutic levels of ASP250 supplementation (pre and post serum pools) have been subjected to comparative fractionation by using gel filtration and affinity chromatography on immobilized Cibacron Blue F3G-A. Comparable serum fractions obtained from pre- and post ASP250 blood sera were assayed in muscle cell culture bioassays designed to measure their effect on proliferation. Pre- and post-ASP250 sera were subjected to gel filtration and divided into the following fractions: fraction 1, Kav less than .17; fraction 2, Kav = .17 to .41; fraction 3, Kav = .41 to .59. Post-ASP250 fractions 2 and 3 increased proliferation rate in cultured muscle cells to a greater extent than comparable pre-ASP250 fractions (P less than .001). Chromatography of fraction 3 on immobilized Cibacron Blue F3G-A showed that both pre- and post-ASP250 fraction 3 contained a putative inhibitor of myogenic cell proliferation as well as mitogenic factors. However, negative growth factor activity was greater in pre-ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05). Additionally, positive growth factor activity was lower in pre ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05). These data suggest that levels and(or) activities of both positive and negative muscle growth factors in serum may be altered by the addition of antimicrobials to the diets of growing pigs. PMID- 2262416 TI - In vivo prediction of extracellular and intracellular water in cattle and sheep using thiocyanate and urea. AB - Two experiments were conducted in cattle and sheep to determine the earliest time for thiocyanate equilibration with extracellular water. In Exp. 1, nine animals were infused to determine marker concentrations and sampling times. In Exp. 2, five steers were infused and then exsanguinated for tissue analyses. Thiocyanate equilibrated 22 to 31 min after infusion with a pool size equivalent to expected extracellular water. Plasma thiocyanate half-life averaged 29 h. Tissue concentrations 24 or 48 h after thiocyanate infusion were 20 to 24% of those observed in plasma for heart muscle and kidney and 6 to 8% in liver and skeletal muscle. A procedure is proposed for the in vivo estimation of empty body water (urea dilution), extracellular water (thiocyanate dilution) and, by difference, intracellular water in cattle and sheep, requiring only three blood samples, an initial sample and two samples taken 12 and 28 min after intravenous infusion of a urea-thiocyanate solution. PMID- 2262417 TI - Effects of high-temperature conditioning on enzymatic activity and tenderness of Bos indicus longissimus muscle. AB - We studied the effects of high-temperature conditioning (HTC) on beef longissimus (LM) and semitendinosus muscles. Eleven 5/8 Sahiwal x Angus, Hereford or Angus x Hereford crosses (seven heifers and four steers) were slaughtered. Alternate carcass sides were held at 22 +/- 3 degrees C for 6 h, then chilled at -1 degree C for 18 h. The opposite, control (C) sides were chilled at -1 degree C for 24 h. Samples were removed only from the LM at various times to determine calcium dependent protease (CDP) and CDP inhibitor (INH) activity, cathepsins B and B + L activity, shear-force, sensory panel traits, myofibrillar fragmentation index (MFI) and sarcomere length. Results were analyzed by least squares procedures; our model included fixed effects of temperature, sex and their interaction. The LM temperature remained higher (P less than .01) for the HTC treatment at 3, 6, 9 and 12 h postmortem. In addition, HTC increased the rate of pH decline which resulted in pH differences (P less than .01) at 6, 9 and 12 h. At d 1, LM steaks had lower (P less than .05) shear forces (8.3 vs 9.6 kg) from HTC than C carcasses. At d 14, LM shear forces tended (P = .13) to be lower for HTC (6.9 kg) than for C (7.7 kg) carcasses. At, 3, 7 and 14 d, MFI for LM were greater (P less than .07) for the HTC steaks. However, by 6 h postmortem, INH activity had decreased (P less than .10) 35% in HTC samples, but no change had occurred in C samples (P less than .10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262418 TI - Bone ossification and carcass characteristics of wethers given silastic implants containing estradiol. AB - Administration of growth promotants with estrogenic activity via hastening closure of the growth plate could have an economic impact on lambs because closure results in ovine carcasses being classified as yearlings. Twelve wether lambs approximately 12 mo old were given silastic implants filled with estradiol 17 beta and allotted randomly to be slaughtered 30, 60, 90, or 220 d after implantation to determine time of growth plate closure in relation to date of implanting. Seven comparable wethers not implanted served as controls. Four wethers implanted at 2 mo of age and slaughtered 220 d later also were included. Implanted wethers had serum concentrations of estradiol averaging 13.9 pg/ml over the 220-d implant period; controls averaged 2.7 pg/ml. Estradiol implants increased carcass maturity scores but fat deposition was not altered. Growth plate widths decreased (P less than .05) as wethers grew older and implants were in place for longer periods of time. Metacarpal growth plates in 12-mo-old lambs were completely ossified 220 d after implanting, but control wethers and wethers implanted at 2 mo maintained growth plate widths. Neither metacarpal nor metatarsal bone lengths differed (P less than .05) between control and implanted wethers. Growth plate ossification was not complete until 570 d of age in implanted lambs, even though bone length had stopped increasing by 408 d. Therefore, even though estradiol and other growth stimulants with estrogenic activity increase rate of ossification of the metacarpal growth plate, bone length or mature size is not limited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262419 TI - Interactions between the beta-adrenergic agonist salbutamol and genotype on meat quality in pigs. AB - Salbutamol (2.7 ppm) fed to pigs between weaning and slaughter increased ADG (5%), dressing percentage (2%) and cross-sectional area of the longissimus (LD) muscle (14%). In fatter, White-line-sired pigs, but not in leaner, Meat-line sired animals, it reduced backfat thickness (25%). Liver weight and glycogen concentration also were decreased. In neither genotype were there effects of Salbutamol on pH45, drip loss or reflectance value of the LD, but ultimate pH was elevated in semimembranosus (SM), adductor (AD) and supraspinatus (SS) muscles, resulting in reduced color saturation values. Total muscle heme pigment concentrations were reduced by 10 (SS) to 19% (LD and SM) and the intramuscular fat concentration of the AD, but not the LD, was reduced by 21%. Treated pigs had LD and SM muscles that when measured instrumentally were 15 and 8% tougher, respectively, after cooking, but the texture of the SS was not significantly altered by treatment. Salbutamol increased plasma lactate and creatine phosphokinase (CPK) concentrations. Compared with White-line-sired animals, Meat line-sired pigs had a higher dressing percentage (2%) and LD muscles with larger cross-sectional area (13%). They also had higher circulating CPK levels. PMID- 2262420 TI - Effect of postmortem treatments on the tenderness of meat from Hereford, Brahman and Brahman-cross beef cattle. AB - The effect of postmortem aging (7, 14, 21 or 28 d), high-voltage electrical stimulation (stimulated or not stimulated) and blade tenderization (none or once; crossbreds only) on the sensory and cooking properties of meat from four beef breeds or breed-types (purebred Hereford, purebred Brahman, Hereford x Brahman and Brahman x Hereford) was determined. The meat from purebred Brahman cattle that was not electrically stimulated was less tender and more variable in tenderness than that from other breed-types but electrical stimulation reduced these differences in tenderness. The Brahman crossbred steers produced meat that was not different in tenderness or variability in tenderness from that of purebred Hereford steers, although all were only judged "slightly tender." Electrical stimulation reduced the length of postmortem aging needed to reach a given level of tenderness regardless of breed or breed-type. Meat from crossbred animals that was blade-tendernized was not different in tenderness from meat that was electrically stimulated. The results of this investigation indicate that purebred Brahman muscle was inherently less tender, but postmortem tenderization procedures produced meat that was similar tenderness to that of the other breed types used in this study. PMID- 2262421 TI - Effect of dietary electrolyte balance on nutrient digestibility determined at the end of the small intestine and over the total digestive tract in growing pigs. AB - A replicated 4 x 4 Latin square digestion trial was conducted to determine the effect of electrolyte balance (EB = Na + K - Cl meq/kg of the diet) on apparent nutrient digestibilities in pigs fitted with ileal T-cannulas. Experimental diets were composed of corn and soybean meal with dietary EB altered by the substitution of CaCl2 for CaCO3, or NaHCO3 for corn and soybean meal. Electrolyte balance levels examined were -50, 100, 250 or 400 meq/kg of the diet. Increasing dietary EB concentration linearly increased (P less than .05 to P less than .02) apparent ileal digestibility of N, energy, DM and all amino acids, except alanine and methionine. However, nutrient and amino acid digestibilities measured over the total digestive tract were similar (P greater than .16) among EB levels. Increasing dietary EB resulted in a linear and quadratic (P less than .03) effect on daily urinary N excretion, resulting in a linear (P less than .05) improvement in N retention expressed both as a percentage of N intake and of absorbed N. Blood pH, total CO2, HCO3 and base excess concentrations increased linearly (P less than .02 to P less than .001) with increasing dietary EB. Dietary EB concentrations influenced nutrient and amino acid absorption measured near the end of the small intestine. Additionally, the N balance data per unit of N intake or N absorbed are indicative of an improved N utilization in pigs fed increasing dietary EB concentrations from -50 to 400 meq/kg. PMID- 2262422 TI - Effect of fat sources and combinations on starter pig performance, nutrient digestibility and intestinal morphology. AB - Three growth trials and one digestion trial were conducted to compare the effect of dietary fat sources and combinations on starter pig performance, nutrient digestibility and intestinal morphology. Growth trials 1 and 2, utilizing a total of 324 weanling pigs (21 +/- 3 d), were conducted to determine the influence of addition of soybean oil, coconut oil, choice white grease, 50% soybean oil: 50% coconut oil or 50% choice white grease: 50% coconut oil on starter pig performance. Diets were supplemented with 10% fat for the first 2 wk of the study and with 5% for the final 3 wk. The third growth trial, utilizing a total of 210 weanling pigs, was conducted to evaluate the effects of addition of soybean oil, coconut oil, 50% soybean oil: 50% coconut oil, 75% soybean oil: 25% coconut oil or 25% soybean oil: 75% coconut oil on starter pig performance and nutrient digestibility. Average daily gain and feed/gain were not changed during wk 0 to 2, but they were improved from 3 to 5 wk postweaning when fat was added to the diets. The combination of 50% soybean oil and 50% coconut oil resulted in higher ADG than the other fat combinations. A digestion trial utilizing 24 weanling pigs (21 +/- 3 d) was conducted to evaluate the effects of soybean oil, coconut oil, or combination of soybean oil and coconut oil on morphology of the small intestine and ileal and total tract apparent digestibilities of individual fatty acids, total fatty acids, N, DM and GE from d 5 to 8 postweaning. Pigs fed the combination of soybean oil and coconut oil tended to have increased (P less than .08) villus height compared with pigs fed soybean oil or coconut oil alone. Micrographs revealed intestinal morphology with long, round villi when this combination of oils was fed. These trials demonstrated that a combination of soybean oil and coconut oil improved (P less than .05) pig growth performance over coconut oil alone or with added choice white grease and tended to improve (P less than .12) ileal digestibility of medium-chain fatty acids (less than or equal to 14 C) compared to diets without added fat or containing soybean oil or coconut oil alone. PMID- 2262423 TI - Changes in morphology, cell number, cell size and cellular estrogen content of individual littermate pig conceptuses on days 9 to 13 of gestation. AB - Days 9 to 12 of gestation in the pig are marked by a pronounced asynchrony among littermate embryos. Previously published studies have suggested that the most advanced embryos within a litter by d 12 synthesize greater amounts of estrogen. Embryonic estrogen secretion has been shown to advance endometrial secretions, which may adversely affect less-developed littermates. To date, however, no comprehensive study of the developmental pattern and synthetic activities of individual littermate embryos during this period has been conducted. Litters were collected from Yorkshire gilts on d 9 (n = 11), 11 (n = 10), 12 (n = 5) and 13 (n = 8). Size (greatest diameter), DNA content (cell number), protein:DNA ratio and estrone (E1) and estradiol-17 beta (E2) content were determined for each embryo. Embryo sizes (mm greatest diameter) were (x +/- SEM) 1 +/- .1, 5.6 +/- .7, 41.2 +/- 11.7 and 405.7 +/- 16.7 on d 9, 11, 12 and 13, respectively. The daily variation in embryo size, expressed as CV was 82% on d 9, 145% on d 11, 206% on d 12 and 46% on d 13. DNA per embryo increased progressively from d 9 to 13, whereas the protein:DNA ratio declined. Content of E1 and E2 per embryonic cell was greatest on d 11 and d 12 before declining markedly on d 13. Cell number and embryo size were correlated positively in embryos 1 to 7 mm (P less than .01) and embryos greater than 100 mm (P less than .01) but not in embryos 8 to 100 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262424 TI - Insulin responsiveness to glucose and tissue responsiveness to insulin over the feeding cycle in sheep. AB - Insulin responsiveness to glucose and tissue responsiveness to insulin, using the hyperglycemic clamp and the hyperinsulinemic euglycemic clamp techniques, were measured before, during and after feeding in sheep fed an alfalfa hay and commercial concentrate diet. Glucose infusion rate and the plasma insulin increment in the hyperglycemic clamp experiment were higher during the feeding period (0 to 1 h after initiating feeding) than during the pre- and post-feeding periods. The ratio of plasma insulin increment to glucose infusion rate remained unchanged over the feeding cycle. Only a slight increase (P less than .05) in the glucose infusion rate was observed during feeding in the hyperinsulinemic euglycemic clamp experiment. These results suggest that insulin responsiveness to glucose tends to be enhanced during the feeding period but that tissue responsiveness to insulin is not changed over the feeding cycle in sheep. PMID- 2262425 TI - Active immunization of beef heifers against luteinizing hormone: I. Evaluation of protein carriers and adjuvants on antigenicity of LH. AB - Two experiments were conducted to evaluate two carrier proteins and nine adjuvants in promoting antibody production in heifers immunized against LH. The anti-LH antibody response was evaluated in heifers immunized against LH conjugated to either ovalbumin or keyhole limpet hemocyanin (KLH) (Exp. 1). In Exp. 2, an LH-ovalbumin conjugate was used to evaluate effectiveness of nine different adjuvants in antibody production. Weekly blood samples were collected from all heifers throughout the 23-wk study to determine LH antibody binding activity. In Exp. 1, heifers immunized with the LH-ovalbumin (LH-oval) conjugate had greater LH antibody binding activities (P less than .001) than those immunized with the LH-KLH conjugate. In Exp. 2, nine groups of heifers were immunized with LH-oval suspended in one of nine adjuvants; a 10th group was immunized against ovalbumin alone (control). Only adjuvants that contained at least 40% oil resulted in LH antibody binding activity that differed (P less than .01) from control. These results show that ovalbumin was a superior carrier protein to KLH in enhancing antibody production; adjuvants with greater than 50% oil were superior to those with less oil in promoting LH antibody production. PMID- 2262426 TI - Active immunization of beef heifers against luteinizing hormone: III. Evaluation of dose and longevity. AB - Objectives were to evaluate the dose (Exp. 1) and purity of LH preparations (Exp. 2) on the anti-LH antibody response in heifers. Experiment 3 evaluated the longevity of LH immunization on sterility in heifers. In Exp. 1, 115 crossbred heifers were injected every 3 wk for 6 wk with .1, .33, 1.0, 3.0 or 9.0 mg of LH ovalbumin. Concentrations of anti-LH antibodies generated were quantified by determining the percentage of binding of [125I]LH in serum. Mena LH binding over wk 0 to 12 was greater in heifers immunized with 1.0 mg conjugate than in heifers immunized with other doses (P less than .05). In Exp. 2, LH-ovalbumin conjugates were made from either LH-1, LH-2 or LH-3, which had relative immunological potencies of 2.1, 1.5 and 1.2 x NIH-LH-S1 units/mg, respectively. Forty-eight crossbred beef heifers were immunized against one of these three LH-ovalbumin conjugates, against LH conjugated without ovalbumin (LH-LH), or against ovalbumin alone (Oval). Estrous cycle activity was monitored by measuring serum progesterone concentration. Potency of the LH preparation used in the LH ovalbumin conjugate was correlated (r = .94) with its ability to produce LH antibodies. In Exp.3, heifers were injected with 1 mg antigen every 2 wk for 10 wk. Five LH-1 heifers and five control heifers were slaughtered for examination of ovaries 10 wk after the last booster injection. The remaining five LH-I and five control animals were placed with a bull 8 wk after the last booster. All five control heifers conceived by 4 +/- 1 wk after placement with the bull whereas the LH-immunized heifers remained acyclic for 42 to 96 wk. PMID- 2262427 TI - Bioavailability of magnesium in beef cattle fed magnesium oxide or magnesium hydroxide. AB - Two experiments were conducted to compare Mg bioavailability from Mg oxide (MgO) vs Mg hydroxide (Mg(OH)2) fed in either a completely mixed diet or a mineral supplement. In Exp. 1, these Mg sources were incorporated into completely mixed diets and offered to 15 steers (282 kg) allotted to three treatments: control diet containing .19% Mg, control plus .2% added Mg as MgO, or control plus .2% added Mg as Mg(OH)2. Each calf was fed 5 kg/d of the respective diet during 10-d adjustment and 7-d collection periods. Blood samples were collected on d 1, 3 and 7. Mg supplementation increased (P less than .01) fecal and urinary Mg excretions, whereas apparent Mg absorption (%) and retention were similar (P greater than .10) for all treatments. Plasma Mg concentrations were similar (P less than .10) for calves supplemented with MgO and Mg(OH)2 but were higher (P less than .05) for Mg supplemented than for control calves on d 7. In Exp. 2, these Mg sources were incorporated into mineral supplements and offered free choice to 30 spring-calving beef cows gazing tetany-inducing pastures from March 6 to May 1. Each of three groups of 10 cows was assigned to a 5.7-ha tall fescue pasture and offered either a control supplement or a supplement containing 40% MgO or Mg(OH)2. Blood samplers were collected on d 0, 7, 14, 28, 42 and 56. Plasma Mg concentrations were not different (P greater than .10) for cows offered MgO and Mg(OH)2 but were higher (P less than .01) for Mg-supplemented than for control cows on d 28, 42 and 56.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262428 TI - Utilization of nitrogen and energy by Holstein steers fed formaldehyde- and formic acid-treated alfalfa or orchardgrass silage at two intakes. AB - Our objective was to measure the utilization of energy (E) and N by Holstein steers when fed alfalfa and orchardgrass silages offered at 65 and 90 g DM/kg live weight (LW).75 daily. Twelve steers adapted to the Beltsville respiration chambers were assigned to three Latin squares with 42-d periods. Steers in one square had permanent catheters in the portal and two mesenteric veins. Energy and N balance were measured during a 7-d collection of feces and urine that included a 3-d measurement of respiratory exchange. Energy and N variables were not different between catheterized and uncatheterized steers. Apparent digestibilities of DM, OM, CP, neutral detergent solubles and permanganate lignin were higher (P less than .01) and digestibilities of NDF and ADF, hemicellulose and cellulose were lower (P less than .01) for steers consuming alfalfa compared to orchardgrass silage. When fed alfalfa, steers' daily gross energy intake, DE, urine energy, ME, heat production and tissue energy retention were greater (P less than .01) and fecal energy losses were less (P less than .01) than when they were fed orchardgrass. Partial efficiency of ME use for tissue energy (TE) was greater (P less than .01) for steers when fed alfalfa (46.1%) than when fed orchardgrass (35.6%). Apparent ME (kcal/LW.75) required for maintenance of TE was similar for steers when fed alfalfa (133.9) and orchardgrass (131.2) silages. Nitrogen retention (g/d) was 48% greater (P less than .01) for steers when fed alfalfa (30.6) than when fed orchardgrass (20.7). This study demonstrates that steers used ME from alfalfa more efficiently for TE deposition than ME from orchardgrass. PMID- 2262429 TI - Blockade of satiety factors by central injection of neuropeptide Y in sheep. AB - The ability of neuropeptide Y (NPY) to stimulate feed intake was tested in combination with two treatments known to depress feed intake in sheep. Six ewe and three wether lambs (mean BW = 40 kg) fitted with lateral cerebral ventricular guide cannulas and ruminal cannulas had free access to a nutritionally complete, pelleted diet. Balloons placed into the rumen were filled with either 0, 30 or 60 ml of water/kg BW and left in place for 6 h; intake was measured. Based on the decline in feed intake observed with increasing balloon volume in the rumen, Exp. 2 was designed to test effects of NPY injection (0 or 3.0 nmol) into the lateral cerebral ventricle and ruminal distension (0 or 35 ml/kg BW) for 6 h. During the 6-h test period, feed intake was depressed (P less than .05) by intraruminal balloon distension, but feed intake was increased by NPY injection (P less than .05); no interaction between NPY and distension was detected. Ruminal evacuation revealed that digesta occupied only 43% of the rumen's total volume capacity. Balloons occupied 14% of capacity, whereas meal size in control sheep following a 1.5-h fast equaled 7% of capacity. In Exp. 3, intraruminal infusion of 8 mmol/min of propionate depressed (P = .11) feed intake, whereas NPY injection enhanced (P less than .05) intake. There was no interaction between NPY and propionate infusion. In none of these experiments was cumulative feed consumption at 24 h influenced. We conclude that NPY is a versatile feeding stimulant. It promotes feed intake in feed-satiated, ruminally distended and propionate-infused sheep. PMID- 2262430 TI - Effects of rapeseed silage variety and dietary level on digestion and growth performance of beef steers. AB - A digestion and ruminal fermentation trial involving five ruminally cannulated steers assigned to a 5 x 5 Latin square with a 2 x 2 + 1 arrangement of dietary treatments was conducted to evaluate the effects of variety of rapeseed silage (RS) containing either a high (HG) or a low (LG) glucosinolate concentration when fed at 100 or 50% of diet DM. A bromegrass hay-corn-soybean meal mixture, which was expected to be isocaloric and isonitrogenous with the RS, was used as the control (C) treatment and replaced RS in the 50% diets. In situ disappearance of substrate from both RS varieties was measured in ruminal environments created by each diet. No dietary treatment x RS substrate interactions were observed for any in situ variable. Total tract digestibility and extent of in situ disappearance of both DM and NDF were greater (P less than .01) for HG than for LG. In situ DM and NDF disappearance at 8, 16 and 24 h was greater (P less than .01) for RS than for the C diet. Similarly, total tract DM digestibility was greater (P less than .01) for RS (61.0%) vs C (56.0%) diets. Diets with 50% RS had greater (P less than .01) NDF digestibility (50.4%) than 100% RS (43.6%) diets. Variety of RS had no effect on particulate passage rate. In a 77-d growth trial with 60 beef steers, ADG was greater (P less than .01) for HG vs LG (.46 vs .36 kg), 50 vs 100% (.52 vs .31) and C vs RS (.64 vs .41) diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262431 TI - Digesta kinetics, ruminal fermentation characteristics and serum metabolites of pregnant and lactating ewes fed chopped alfalfa hay. AB - Eight ruminally cannulated ewes (four control and four bred; average BW = 85.7 kg), limit-fed alfalfa hay (1.86% BW), were used in two experiments to determine the effects of pregnancy and lactation on digestive function and serum metabolites. Seven-day sampling periods were used starting on d 102, 118 and 132 of gestation (Exp. 1) and d 14 and 32 of lactation (Exp. 2). Particulate (6.8 vs 4.9%/h; PPR) and fluid passage rates (13.9 vs 10.9%/h) were greater (P less than .05) and gastrointestinal mean retention time (28.9 vs 35.7 h) and fluid turnover time (FTT, 7.5 vs 9.5 h) were lesser (P less than .05) in pregnant than in nonpregnant ewes, respectively. Isobutyrate concentration was lower (P less than .05) in pregnant (1.7 mol/100 mol) than in nonpregnant (1.9 mol/100 mol) ewes. No differences (P greater than .10) were noted for any other ruminal fermentation measures between pregnant and nonpregnant ewes. In Exp. 2, no differences (P greater than .10) were noted in digesta kinetics or ruminal fermentation measures except for isobutyrate and isovalerate molar proportions and serum urea N (SUN) concentration. Isobutyrate, isovalerate and SUN concentrations (21.8 vs 26.1 mg/dl) were lower (P less than .05) in lactating ewes than in nonlactating ewes. Gastrointestinal fill (5.7 vs 7.7 g/kg BW) and FTT (9.3 vs 12.7 h) were lesser and DM digestion (66.7 vs 57.4%) was greater (P less than .05) in lactating than in nonlactating ewes. Data suggest that, during pregnancy, passage rate increases occur without affecting DM digestion and that, during lactation, PPR is not affected when ewes are limit-fed. PMID- 2262432 TI - The influence of physiological state and dietary nitrogen supply on digestion in the dairy cow. AB - The effects of N supply on digestion were compared in cows in late pregnancy vs early lactation. Two groups of four and one group of three dairy cows received, during a digestion trial, corn silage-concentrate diets (65:35) differing in N supply. Concentrates were formulated so that diets were either insufficient (Diet 1) or sufficient (Diets 2 and 3) in ruminally fermented N and either insufficient (Diets 1 and 2) or sufficient (Diet 3) in protein digestible in the intestines. Experimental periods were 3 wk before and 3 wk after parturition. Organic matter digestibilities were 69.8, 73.1 and 72.5% in late pregnancy vs 64.9, 69.8 and 70.8% in early lactation for Diets 1, 2 and 3, respectively. Digestibility was higher (P less than .05) in late pregnancy than in early lactation. Differences between physiological states were attributed to differences in ruminal digestibility and in fiber digestibility. These differences were not explained by a reduction in large particle retention time, but in situ DM disappearance was reduced in early lactation. Ruminal protozoa concentration and the acetate: propionate ratio decreased between pregnancy and lactation. The duodenal non ammonia N:N intake ratio was higher for Diet 1 than for Diets 2 and 3, 1.20, .97 and .94, respectively, but it did not vary between physiological states. In conclusion, some of the negative consequences of a shortage in degraded N are more dramatic in early lactation than in late pregnancy. PMID- 2262433 TI - Improved enzymatic method to measure processing effects and starch availability in sorghum grain. AB - A modified enzymatic method to measure processing effects and starch availability in steam-flaked sorghum grain (SFSG) was developed. To establish the method, experiments were conducted to determine the required enzyme concentration, color reagents, precipitants, sample particle size, shaking frequency and buffer pH. Glucose release at different incubation times (0 to 48 h) from uncooked (UNC) or fully cooked (CK, 100% gelatinized) ground sorghum grain, a 50:50 mixture of UNC and CK (C50) and SFSG was determined. Glucose release from UNC, CK and SFSG was expressed as one-component equations with rate constant k and r2 of .119 and .98, 1.781 and .98, and .368 and .99, respectively; C50 was characterized by having two starch components, one with a fast rate constant, 2.624/h, and one with a slow rate constant, .066/h (R2 = .99). Different degrees of gelatinization were obtained by mixing different proportions of CK and UNC. Glucose release from these samples was highly correlated with starch gelatinization (r2 = .99). By adjusting the tension between mill rollers, five SFSG samples with bulk densities ranging from 476 to 283 g/liter (37 to 22 lb/bu) were produced; respective roller mill electrical load ranged from 21 to 51.5 amps. Enzymatic determination of glucose release resulted in values of 422, 512, 588, 618 and 678 mg/g, which were more closely related to bulk density than birefringence measurements. The modified method for starch availability determination was found to be relatively simple, fast and sensitive, and is recommended. PMID- 2262434 TI - Estimating starch availability and protein degradation of steam-flaked and reconstituted sorghum grain through a gas production technique. AB - Five steam-flaked sorghum grain (SFSG) samples with bulk densities of 476, 412, 347, 309 and 283 g/liter made by adjusting tension between mill rollers and three reconstituted sorghum grain (RSG) samples with reconstitution times of 10, 20 and 30 d and a control sample were analyzed for gas production kinetics (rumen liquor fermentation) and enzymatic glucose release (amyloglucosidase). Protein degradation was estimated from 6-h gas production and residual ammonia in the liquid. Gas production followed first-order kinetics (r2 greater than .98; P less than .01) and was used to describe rate and extent of digestion kinetics. Rate of gas production increased as processing degree increased. The magnitude of increase in gas production, however, was much less for RSG than for SFSG. Linear relationships were observed between enzymatic glucose release and the gas production rate constant k as well as gas production at 4,6 and 8 h (r2 greater than .98; P less than .01). Protein degradation decreased with processing degree of SFSG but increased with reconstitution time. A technique based on 6-h gas production and residual ammonia in the liquid is proposed to estimate both ruminal starch availability and ruminal protein degradability for processed sorghum grain. PMID- 2262435 TI - Effects of chewing behavior and ruminal digestion processes on voluntary intake of grass silages by lactating dairy cows. AB - Four primiparous Holstein-Friesian cows (518 kg average BW) with ruminal and duodenal cannulas were used to examine voluntary intake of direct cut (DC) or wilted (W) grass silage in relation to ruminal characteristics and chewing behavior. Dry matter content of the silages was 17.0 and 38.1%, concentrate DM intake was restricted to 5.0 and 5.3 kg/d, and voluntary DM intake from silages averaged 7.4 and 9.5 kg/d (P = .008), respectively. The acetate/propionate ratio in ruminal fluid decreased from 4.0 on DC to 3.3 on W silage (P = .021). The protein content in milk increased from 26.3 to 27.5 g/liter (P = .042) and the protein yield from 469 to 574 g/d (P = .038). The distribution of concentrates (38% of DM intake) with a mean particle size of .04 cm reduced differences in fecal mean particle size between diets. There was a shift from eating to ruminating on W silage with regard to daily duration (min/d) and number of jaw movements (no./d). However, ruminating index (no./kg DM intake) remained unchanged, irrespective of wilting and chop length of the silages or physiological state of the animals. These results are interpreted to indicate that the time lag for functional density of feed particles in the reticulorumen to increase, as affected by ruminating activity, not rate of reduction of the particle size, limits voluntary intake of grass silage by cattle. PMID- 2262436 TI - Propionic acid disappearance from the foregut and small intestine of the beef steer. AB - Studies were conducted to determine the disappearance of propionic acid from the rumen and across the small intestine. Four crossbred beef steers, fitted with ruminal, duodenal and ileal cannulas, were given pulsed-continuous infusions of a nonabsorbable liquid phase marker (CrEDTA) and buffered propionic acid to achieve ruminal propionate productions (RPP) of 142 (basal), 567 and 997 mmol/h. Liquid flows from the rumen, and at the duodenum and ileum (2.75, 3.57 and .92 liters/h, respectively) were not affected by RPP (P greater than .23), although significant differences existed between sites (P = .001), reflecting a net addition of liquid between the rumen and duodenum and a net removal of liquid within the small intestine. Propionate disappearance from the rumen was 40 to 57% irrespective of RPP, with the complement passing from the rumen. Of the propionate that exited the rumen, 93 to 97% disappeared prior to entering the duodenum. Overall removal of RPP prior to the duodenum was 97 to 99% irrespective of RPP. Passage of propionic acid at the duodenum and at the ileum did not differ (P greater than .76) across all RPP, and the overall mean passages did not differ from zero (P greater than .34); similar results were observed for other VFA. These observations indicate that essentially all RPP is removed prior to entering the small intestine. Additionally, net propionate disappearance across the small intestine was undetectable and likely biologically irrelevant. Therefore, VFA absorption does not appear to be a limiting biological process in the beef steer. PMID- 2262437 TI - The alphastat hypothesis in respiratory control and acid-base balance. AB - This selective review 1) evaluates recent interpretations that broaden the definition of the alphastat hypothesis, 2) proposes that central chemoreception and acid-base regulation via ion transport involve proteins conforming to the alphastat hypothesis, and 3) describes, using recent evidence, possible candidates for these proteins. The alphastat hypothesis states that proteins that contain appropriate function-determining titratable groups maintain a constant charge state and unaltered function with temperature-dependent pH changes but can be very sensitive to isothermal pH changes. Appropriate groups, e.g., imidazole histidine, are determined by the pK and the effect of temperature on the pK. The hypothesis explains how protein structure and function can be conserved among a diversity of vertebrate and invertebrate pH values. It also suggests a mechanism for sensing or regulating temperature-independent pH changes, e.g., in central chemosensitivity and transmembrane ion exchange. Possible candidates for such alphastat-conforming proteins include two, the glutamate receptor and the Na(+) H+ antiporter, for which recent evidence indicates the presence of numerous histidines at probable function-determining sites and demonstrates pH sensitivity inhibitable by the histidine blocker diethylpyrocarbonate (DEPC). PMID- 2262438 TI - Distribution of muscle fiber types and EMG activity in cat intercostal muscles. AB - The electromyogram (EMG) activity and histochemical properties of intercostal muscles in the anesthetized cat were studied. The parasternal muscles were consistently active during inspiration. The external intercostals in the rostral spaces and the ventral portions of the midthoracic spaces were also recruited during inspiration. The remaining external intercostals were typically silent, regardless of the level of respiratory drive. The internal intercostal muscles located in the caudal spaces were occasionally recruited during expiration. There was a clear correlation between recruitment patterns of the intercostals and the histochemically defined fiber type properties of the muscles. Intercostal muscles that were routinely recruited during inspiration had a significantly higher proportion of slow-oxidative muscle fibers. PMID- 2262439 TI - Bronchial circulatory reversal of methacholine-induced airway constriction. AB - Although a role for the bronchial circulation in clearance of bronchoactive agents has been frequently proposed, experimental evidence is limited. In this study, we determined the importance of bronchial blood flow (QBA) in the recovery from methacholine-(MCh) induced bronchoconstriction. In 10 pentobarbital anesthetized ventilated sheep, the bronchial branch of the bronchoesophageal artery was cannulated and perfused (0.7 ml.min-1.kg-1) with blood pumped from the femoral artery. MCh was infused directly into the bronchial artery at increasing concentrations (10(-7) to 10(-5) M). MCh infusion caused a concentration dependent increase in airway resistance at constant QBA. However, the time constant of recovery (TC) from airway constriction after cessation of the MCh infusion was not dependent on the MCh concentration or the magnitude of the increases in airway resistance. When QBA was at 50, 100, and 200% of control level, with constant MCh concentration, TC was 44 +/- 6, 25 +/- 2, and 24 +/- 2 (SE) s at each flow level, respectively. TC at 50% of control QBA was significantly greater than at control QBA (P less than 0.01). Thus the magnitude of QBA can alter the time course of recovery from MCh-induced increases in airway resistance. These results document the importance of QBA in reversing agonist induced constriction and suggest that an impaired bronchial circulation may contribute to the mechanism of airway hyperreactivity. PMID- 2262440 TI - Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease. AB - Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP. PMID- 2262441 TI - Splanchnic and muscle fructose metabolism during and after exercise. AB - Regional substrate exchange was studied in 12 healthy males during 90 min of bicycle exercise at 30% of maximal O2 consumption with a 20-min recovery. Six subjects received an intravenous fructose infusion (8.5 mmol/min) from 40 min of exercise to the end of recovery. Splanchnic glucose output, muscle glucose uptake, arterial glucose, and insulin were uninfluenced by the infusion. The respiratory exchange ratio rose to 0.93 +/- 0.04, and arterial free fatty acids fell by 50% (P less than 0.05). Fructose was taken up by splanchnic tissues (45% of administered load), leg muscle (28%), and resting muscle (28%). During infusion, arterial lactate and pyruvate rose two- to threefold, and these substrates were released from splanchnic tissues and taken up by exercising and resting muscle. Splanchnic release of lactate, pyruvate, and glucose accounted for 78% of fructose uptake at 90 min of exercise. Uptake of fructose, lactate, and pyruvate accounted for 55% and together with glucose for 103% of the total oxidative metabolism by exercising muscle. The regional fructose uptakes and lactate exchanges persisted throughout recovery. The present results indicate that fructose infusion during leg exercise 1) results in increased carbohydrate oxidation from fructose, lactate, and pyruvate in exercising muscle, 2) exerts a glycogenic effect in resting muscle and liver during exercise and in liver and muscle recovering from exercise, and 3) does not interfere with glucose metabolism, and that fructose transport into muscle differs from that of glucose. PMID- 2262442 TI - Upper airway resistance and geniohyoid muscle activity in normal men during wakefulness and sleep. AB - Sleep-related reduction in geniohyoid muscular support may lead to increased airway resistance in normal subjects. To test this hypothesis, we studied seven normal men throughout a single night of sleep. We recorded inspiratory supraglottic airway resistance, geniohyoid muscle electromyographic (EMGgh) activity, sleep staging, and ventilatory parameters in these subjects during supine nasal breathing. Mean inspiratory upper airway resistance was significantly (P less than 0.01) increased in these subjects during all stages of sleep compared with wakefulness, reaching highest levels during non-rapid-eye movement (NREM) sleep [awake 2.5 +/- 0.6 (SE) cmH2O.l-1.s, stage 2 NREM sleep 24.1 +/- 11.1, stage 3/4 NREM sleep 30.2 +/- 12.3, rapid-eye-movement (REM) sleep 13.0 +/- 6.7]. Breath-by-breath linear correlation analyses of upper airway resistance and time-averaged EMGgh amplitude demonstrated a significant (P less than 0.05) negative correlation (r = -0.44 to -0.55) between these parameters in five of seven subjects when data from all states (wakefulness and sleep) were combined. However, we found no clear relationship between normalized upper airway resistance and EMGgh activity during individual states (wakefulness, stage 2 NREM sleep, stage 3/4 NREM sleep, and REM sleep) when data from all subjects were combined. The timing of EMGgh onset relative to the onset of inspiratory airflow did not change significantly during wakefulness, NREM sleep, and REM sleep. Inspiratory augmentation of geniohyoid activity generally preceded the start of inspiratory airflow. The time from onset of inspiratory airflow to peak inspiratory EMGgh activity was significantly increased during sleep compared with wakefulness (awake 0.81 +/- 0.04 s, NREM sleep 1.01 +/- 0.04, REM sleep 1.04 +/- 0.05; P less than 0.05). These data indicate that sleep-related changes in geniohyoid muscle activity may influence upper airway resistance in some subjects. However, the relationship between geniohyoid muscle activity and upper airway resistance was complex and varied among subjects, suggesting that other factors must also be considered to explain sleep influences on upper airway patency. PMID- 2262443 TI - Geniohyoid muscle activity in normal men during wakefulness and sleep. AB - Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262444 TI - Relative effects of glycogen depletion and previous exercise on muscle force and endurance capacity. AB - Endurance capacity of human vastus lateralis muscles was observed 24 h after hard exercise followed by either a carbohydrate-restricted or a carbohydrate-loaded diet (depletion and repletion conditions). In a control condition the subjects did no previous exercise and ate their normal diet. Each of these conditions was followed by an experimental protocol in which the five male subjects made a series of alternating 25-s static contractions of each leg at 50% maximal voluntary contraction until one leg failed to achieve the required force (Tlim). Glycogen concentration before the experimental protocol in both legs was significantly lower in the depletion than in the repletion condition. Muscle lactate and creatine phosphate concentrations were within normal limits before the static contractions. The number of contractions the repleted (12.7 +/- 2.2) and depleted (10.3 +/- 1.5) legs could sustain before Tlim were not different from each other, but both were 35% (P less than 0.05) fewer than the control (17.6 +/- 3.0). Surface electromyogram (EMG) amplitude was higher in depleted than in repleted or control muscles. At Tlim, EMG amplitude was maximal, creatine phosphate was 50-70% depleted, and lactate increased fourfold. Average glycogen utilization per contraction in both the repletion and depletion conditions was 5.8 mmol/kg dry wt, but postexercise lactate concentrations were lower in depleted (14.4 +/- 3.6 mmol/kg dry wt) than in repleted (43.2 +/- 7.4) muscles. The EMG frequency distribution shifted downward in all conditions during the experimental protocol and was independent of muscle lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262445 TI - Prostacyclin production with serotonin, increased flow, or elevated venous pressure in dog lung. AB - The lung may release prostacyclin (PGI2) in response to humoral or mechanical stimuli. We measured 6 keto-PGF1 alpha as an index of PGI2 production during serotonin (5-HT) infusion, elevated venous pressure (Pv), or increased blood flow (Q) in the isolated canine lower left lung lobe (LLL). Lobar vascular resistance (LVR) was partitioned into arterial (Ra), middle (Rm), and venous (Rv) components by arterial and venous occlusions. The infusion of 55-210 micrograms/min 5-HT (n = 9) was associated with concomitant increases in PGI2 production and dose related increases in pulmonary arterial pressure (Pa) and LVR. 5-HT increased Ra at each infusion rate, whereas Rm was not changed and Rv was increased only at the highest infusion rate. When Pa was increased by stepwise elevations in Pv from 3.7 to 19.1 cmH2O (n = 8) or by increases in Q from 250 to 507 ml/min (n = 5) to match the Pa increase observed during 5-HT infusion, PGI2 production was not altered. Increases in Pv reduced LVR largely by decreasing Ra, whereas increases in Q reduced LVR without changing Ra, Rm, or Rv. Infusion of 5-HT when Pa was held constant by reduction in blood flow (n = 6) did not increase PGI2. Thus infusion of 5-HT at a normal blood flow rate increased PGI2 formation in the isolated blood-perfused dog lung lobe. The results also suggest that sustained mechanical effects related to increased venous pressure or elevated blood flow are not associated with a sustained elevation of PGI2 formation. PMID- 2262446 TI - Effects of changes in level and pattern of breathing on the sensation of dyspnea. AB - Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort. PMID- 2262447 TI - Supramicron-sized particle clearance from alveoli: route and kinetics. AB - Particles inhaled and deposited in the alveoli of the lung, i.e., distal to the tracheobronchial mucociliary escalator, may theoretically be cleared by several routes, including solubilization, lymphatic drainage, and the mucociliary pathway. We studied the clearance routes and kinetics of an inert insoluble carbonized polystyrene particle of supramicron size (2.85 micron count median diameter) tagged with 57Co (half-life 270 days) in the adult unanesthetized sheep. The rate of particle clearance, assessed by gamma scintillation camera of the whole lung, showed a three-exponential function, comprising a rapid initial phase in the first 44 h of clearance for tracheobronchial deposition followed by a slower phase of mostly alveolar clearance in the next 30 days and a final phase of very slow relatively pure alveolar clearance. A balance study of particle route during clearance and autopsy of regional thoracic lymph nodes, blood, liver, and spleen demonstrated that this supramicron-sized particle cleared from alveoli predominantly via the mucociliary escalator of the tracheobronchial tree. Whole-lung lavage studies showed particle and macrophage recovery rates suggesting a sequestered state for alveolar-deposited particles, which may partly account for their slow clearance rates. The failure to find interstitial penetration by alveolar-deposited particles indicates that the macrophages engulfing these particles, at low particle burdens, travel normally in only one direction, i.e., from interstitium to alveolus and then to the mucociliary escalator. PMID- 2262448 TI - Structural and mechanical adaptations of immature trabecular bone to strenuous exercise. AB - Effects of strenuous exercise on immature bone were examined in two clinically important regions, femoral neck (FN) and lumbar vertebra (L6). Female Sprague Dawley rats (n = 20, 8 wk of age, 150-170 g) were exercised progressively 5 days/wk for approximately 1 h/day for 10 wk at 75-80% of maximum oxygen capacity on a motor-driven treadmill. Caged age-matched rats served as controls (n = 20). Rat FNs were tested in cantilever bending, and vertebral bodies were compressed to 50% of their initial height at a fast strain rate. In response to the strenuous exercise, the relative area of the FN trabecular core increased significantly at the expense of the cortical shell. With that structural change, the exercised FN had significantly less energy to proportional limit than controls. The FN material properties (normal stresses at proportional limit and maximum) were significantly diminished after 10 wk of strenuous exercise. At the same time, no differences were found in vertebral geometry or structural and material properties. In the immature rate, the differential responses of the FN vs. L6 may relate to load history rather than a general systemic response to the strenuous exercise. PMID- 2262449 TI - Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs. AB - Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262450 TI - Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions. AB - Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain. In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors. In this respect its action is similar to hypoxia. To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120 130 days gestation. Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation. In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia. However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min. We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms. PMID- 2262451 TI - Vagal innervation of guinea pig bronchial smooth muscle. AB - We isolated the guinea pig right bronchus with the vagus nerves intact and evaluated the changes in isometric tension of the smooth muscle in response to nerve stimulation. Brief (10-s) trains of electrical field stimulation or vagus nerve stimulation caused a biphasic contraction: the "first phase" sensitive to atropine and the "second phase" sensitive to capsaicin. The two phases could be dissociated by adjusting the stimulus intensity; greater stimulus intensities (pulse durations or voltage) were required to evoke the capsaicin-sensitive phase. When stimulated at 30-min intervals, the magnitude of both phases of the contractions declined over a 2-h period of repeated stimulation; however, this was prevented by indomethacin. Stimulation of the left vagus nerve resulted in a monophasic contraction of the right bronchus, with little evidence of a capsaicin sensitive phase. Blocking neurotransmission through the bronchial ganglion, as monitored by intracellular recording techniques, abolished the first-phase contraction but had no effect on the capsaicin-sensitive phase. Selective blockade of muscarinic M1 receptors had no effect on vagus nerve-mediated contractions. The results demonstrate that the left and right vagus nerves carry preganglionic fibers to the right bronchial ganglion. The right but not the left vagus nerve also carries capsaicin-sensitive afferent fibers that, when stimulated, result in a persistent contraction of the right bronchus. Finally, we provide functional and electrophysiological evidence supporting the hypothesis that capsaicin-sensitive afferent neurons communicate with postganglionic motoneurons within the bronchus. PMID- 2262452 TI - Effect of exercise and obesity on skeletal muscle amino acid uptake. AB - The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle. To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from 10-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]alpha-aminoisobutyric acid (AIB). Muscles from fasted rats were incubated under basal conditions at rest or after a 1-h treadmill run at 8% grade. To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respectively. Muscles were pinned at resting length, preincubated for 30 min at 37 degrees C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O2-5% CO2, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [14C]AIB, and [3H]inulin as a marker of extracellular fluid. Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P less than 0.01), respectively, compared with lean rats. For both lean and obese rats, exercise increased (P less than 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs. EPI 32% and SOL 37%). These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect. PMID- 2262453 TI - Training increases muscle blood flow in rats with peripheral arterial insufficiency. AB - This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals. PMID- 2262454 TI - Late response of the upper airway of the rat to inhaled antigen. AB - We studied the magnitude and time course of changes in upper airway resistance (Ruaw) of actively sensitized Brown-Norway rats after aerosol challenge with ovalbumin (OA). Two weeks after sensitization, eight rats were challenged by inhalation of aerosolized OA through the nose. The airway responses of these rats 5-10 h after OA challenge were compared with those of seven animals challenged with saline. Seven of eight test rats had increased Ruaw, and six displayed discrete late responses (LR). Ruaw during expiration was highly alinear so analysis was confined to Ruaw during inspiration (Ruaw,I). The Ruaw,I averaged over 5 h was 1.262 +/- 0.09 (SE) cmH2O.ml-1.s, 2.6 times the value for saline challenged animals (0.476 +/- 0.143 cmH2O.ml-1.s), and it reached a peak value of 3.454 +/- 0.45 cmH2O.ml-1.s. The time to the peak of the LR was 446 +/- 37.3 min. The duration of the LR in the upper airway was 146 +/- 34.9 min. At the time corresponding to the peak value of Ruaw,I, the lung elastance in the test rats was double the value preceding the peak. Lung elastance was unchanged in the control group. We conclude that inhalation of antigen through the upper airway of the sensitized rat results in a substantial increase in upper airway resistance and a distinct LR. The predominant site of the change in respiratory system resistance is in the upper airway. PMID- 2262455 TI - Effect of exercise conditioning on excitation-contraction coupling in aged rats. AB - We studied aged (24-26 mo) Fischer 344 rats after they underwent 8 wk of moderate exercise conditioning. Right ventricular papillary muscles were loaded with the calcium indicator aequorin. Electrophysiological recordings were also performed. Time to peak isometric tension in muscles from exercised aged rats (EAR) was shorter than in those from unexercised aged rats (UAR) (126 +/- 7 vs. 167 +/- 7 ms; P less than 0.01). Time to 50% relaxation from peak isometric tension was also shorter in EAR than in UAR (88 +/- 3 vs. 119 +/- 12 ms; P less than 0.05). There was a trend toward decrease in time to peak light and a significant decrease in time to 50% decline from peak light (33 +/- 4 ms in EAR vs. 59 +/- 17 ms in UAR; P = 0.001). Action potential amplitude was smaller in EAR than in UAR (67 +/- 4 vs. 82 +/- 3 mV; P = 0.003); however, action potential duration was longer (137 +/- 6 ms in EAR vs. 100 +/- 10 ms in UAR; P = 0.005). Right ventricular-to-body weight ratios revealed no evidence of hypertrophy in EAR compared with UAR. Cardiac tissue norepinephrine content was significantly greater in EAR than in UAR (1,212 +/- 25 vs. 630 +/- 105 ng/tissue; P = 0.02). In summary, exercise reversed the age-related prolongation of isometric contraction and associated intracellular calcium transient in the aged rat while it prolonged the transmembrane action potential. In addition, exercise in aged rats resulted in an increase in cardiac norepinephrine content. PMID- 2262456 TI - Respiratory input impedance in anesthetized paralyzed patients. AB - Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube. Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz. From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz. Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz. Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz. We interpreted Zrs data in terms of a T network mechanical model. We represented the proximal branch by central airway resistance and inertance. The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility. The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues. When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al. (J. Appl. Physiol. 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated. The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity. Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties. PMID- 2262457 TI - Compensation of respiratory alkalosis induced after acclimation to simulated altitude. AB - Conscious intact rats previously acclimated for 3 wk to barometric pressure of 370-380 Torr (3WHx) were made alkalotic for 3 h by a decrease in inspired O2 fraction from 0.10 to 0.075 at ambient barometric pressure (730-740 Torr). Controls were normoxic littermates (Nx) in which inspired O2 fraction was lowered from approximately 0.21 to 0.10 for 3 h. Arterial PCO2 decreased progressively and similarly in both groups (65-70% of control at 15 min). Initially, arterial pH increased less in 3WHx (0.09 +/- 0.004 vs. 0.15 +/- 0.008). As hypocapnia continued, delta[HCO3-]/delta pH (mmol.l-1.pH) became more negative in Nx, from 15.2 +/- 2.5 at 15 min to -37.0 +/- 2.9 at 3 h, indicating nonrespiratory compensation of alkalosis. In 3WHx, delta[HCO3-]/delta pH did not change during alkalosis. Cumulative renal excretion of base (mueq/100 g) during alkalosis increased by 73.2 +/- 11.1 in Nx and 25.4 +/- 7.3 in 3WHx. This difference was mainly due to a larger increase in HCO3- excretion in Nx. The data suggest that the smaller compensation of hypocapnic alkalosis in 3WHx is partly due to the smaller increase in renal base excretion. Because base availability limits renal base excretion, the smaller renal response of 3WHx may be secondary to the low plasma HCO3- concentration that accompanies altitude acclimation. PMID- 2262458 TI - Centrifugal intensity and duration as countermeasures to soleus muscle atrophy. AB - Mechanical acceleration is a countermeasure that may be employed to prevent atrophy of slow-twitch muscle during non-weight bearing. In the present study, daily centrifugation of rats for different durations (1 or 2 h) and at different gravitational intensities (1.5 or 2.6 G) was used to test whether mechanical acceleration could ameliorate the atrophy of the soleus muscle induced by non weight bearing (tail-traction model). The soleus muscle atrophied 32% during 7 days of non-weight bearing without countermeasures. Centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Non-weight-bearing groups receiving 2-h daily treatments of 1, 1.5, or 2.6 G had 48, 56, and 65%, respectively, of the atrophy observed in the non weight-bearing-only group compared with the precontrol group. No evidence was obtained that centrifugation at 2.6 G was more effective than exposure to 1 or 1.5 G as a countermeasure to non-weight-bearing-induced atrophy of the soleus muscle. PMID- 2262459 TI - Theophylline minimally alters contractile properties of canine diaphragm in vitro. AB - We examined the effects of theophylline on contractile properties and high frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations. PMID- 2262460 TI - Body water and electrolyte responses to acetazolamide in humans. AB - Acetazolamide (ACZ), a potent carbonic anhydrase inhibitor, is a known diuretic and causal agent in metabolic acidosis. Its diuretic qualities are well established with respect to urine flow and electrolyte excretion. However, the impact of ACZ on body hydration status has not been adequately quantified. Thus, to establish the influence of ACZ treatment on body water, nine healthy males were evaluated for hydration status after clinically prescribed doses of ACZ. The drug was administered in three 250-mg oral doses 14, 8, and 2 h before determination of body water compartments. ACZ led to a significant 1.7-liter reduction in total body water (3.4%). A significant reduction in extracellular water of 3.3 liters is partitioned as the loss of total body water and a significant increase in intracellular water (1.6 liters). Venous blood pH and plasma HCO3- were significantly reduced 0.09 units and 5.9 mM, respectively, with ACZ. Plasma protein concentration was increased, but plasma osmolality did not change. Plasma Na+, K+, and Cl- concentrations were not different with ACZ, but total electrolyte content was significantly decreased 45.2, 1.17, and 44.1 meq, respectively, for all three. Urine K+, HCO3-, flow, and pH were elevated after ACZ treatment, whereas Na+ and Cl- were the same as placebo levels. In conclusion, acute clinical doses of ACZ reduce body fluid compartments, leading to a moderate isosmotic hypovolemia with an intracellular volume expansion as well as metabolic acidosis. PMID- 2262461 TI - Acetazolamide alters temperature regulation during submaximal exercise. AB - Acetazolamide (ACZ), a potent carbonic anhydrase inhibitor, is known to decrease submaximal exercise tolerance under normoxic and hypoxic conditions. These decrements in performance occur despite the maintenance of O2 consumption and CO2 removal. Because ACZ is a diuretic, it induces a moderate hypohydration that may have a role in reducing the ability to sustain exercise through cardiovascular and thermoregulatory impairment. To investigate this potential impairment, seven healthy males between 21 and 35 yr of age were studied in a double-blind crossover design (placebo vs. ACZ). ACZ was administered in three 250-mg oral doses 14, 8, and 2 h before exercise. Subjects exercised at 70% peak O2 uptake for 30 min on a cycle ergometer in a normoxic thermoneutral environment (25 degrees C, 40% relative humidity). Results indicate that exercise minute ventilation was greater but O2 uptake, CO2 output, and respiratory exchange ratio did not differ with ACZ. ACZ led to lower mean skin (0.7 degrees C), higher rectal (0.6 degrees C), and higher mean body temperatures (0.4 degrees C) after 30 min of exercise. Whole-body sweat loss was reduced 23%, and heat storage during the exercise bout was increased 55%. Stroke volume decreased 25%, and arteriovenous O2 difference increased 15%. A significant inverse relationship (r = -0.63) between heart rate and stroke volume was observed. It is concluded that previously reported decreases in the ability to sustain submaximal exercise with ACZ may be related to hypohydration-induced impairment of the cardiovascular and thermoregulatory systems. PMID- 2262462 TI - In vivo study on medullary H(+)-sensitive neurons. AB - Using the micro pressure ejection technique, we examined responses of medullary neurons with nonphasic discharges (164 units) to direct application of acidified mock cerebrospinal fluid (CSF, pH 6.85-7.05) in decerebrated spontaneously breathing cats. We found 16 H(+)-sensitive cells; they were excited promptly on application of approximately 500 pl of acidified mock CSF in the vicinity of the neuron under investigation, whereas they were unaffected by microejection of the control mock CSF (pH 7.25-7.60). Of the 16 H(+)-sensitive cells, 10 units were further found to be excited by transcapillary stimulation of the central chemoreceptors by using a method of intravertebral arterial injection of CO2 saturated saline. The discharges increased in a similar time course to that of ventilatory augmentation. Distributions of these 10 specific H(+)-sensitive cells were found in the vicinity of nucleus tractus solitarii as well as deep in the ventrolateral medulla. The present results suggest a possibility that pH dependent central chemoreceptors, if any, would be located in two distinct medullary regions described in this study. PMID- 2262463 TI - Interdependence of regional expiratory flows limits alveolar pressure differences. AB - Wilson et al. (J. Appl. Physiol. 59:1924-28, 1985) have asserted that interdependence of regional expiratory flows could cause differences of interregional alveolar pressures to relax to time-independent limits during forced deflation. To test the hypothesis that such limiting differences do arise, we examined regional alveolar pressures during complete and partial maximally forced deflations of six excised canine lungs. Alveolar pressures were monitored using alveolar capsules on each of six lobes during forced deflations initiated at transpulmonary pressures of 30, 20, 15, and 10 cmH2O. In all lungs and in all maneuvers, interregional heterogeneity of alveolar pressure increased rapidly early in the deflation but much less so or not at all later in the deflation. When we compared complete with partial forced deflations, 16 of 24 maneuvers in six lungs showed clear evidence that as deflation progressed the degree of heterogeneity at isovolumic points became independent of the transpulmonary pressure from which the deflation was initiated. That is, alveolar pressures relaxed to limiting interregional differences that did not depend on time elapsed from the onset of the deflation. These data offer strong evidence of the existence of limiting differences. Such behavior implies that the sequence of regional emptying is controlled by a competition of opposing influences: nonuniformities of airway and parenchymal properties promoting nonuniformity of emptying vs. interdependence of regional expiratory flows promoting uniformity. As nonuniformity of regional pressures grows so do those factors that oppose that nonuniformity. These data underscore the insensitivity of maximum expiratory flow volume curve configuration to the underlying inhomogeneous pattern of regional lung emptying. PMID- 2262464 TI - Human auditory brain stem response during induced hyperthermia. AB - A continuous monitoring of auditory brain stem response (ABR) and esophageal (Tes) and rectal temperatures (Tre) were recorded in male undergraduate subjects to investigate a relationship between the interpeak latencies (IPLs) and core temperature. The average change of Tes (36.8-39.5 degrees C) was achieved by immersing the subjects in a temperature-controlled water bath (30-42 degrees C). The IPLs became shorter with the rise in body temperature and were correlated with both Tes and Tre. The average slopes for IPL(I-III) and IPL(I-V) were significantly higher than those for IPL(III-V). The present study of humans indicated that changes of IPL(I-III) and IPL(I-V) were 0.11 and 0.16 ms, respectively, per 1 degree C change in core temperature during induced hyperthermia. PMID- 2262465 TI - Effects of carotid denervation and decerebration on ventilatory response to CO. AB - To clarify the mechanisms involved in the ventilatory response to the inhalation of low concentrations of CO (0.18-0.22% in air), the roles of the arterial chemoreceptors and the forebrain structures have been investigated in unanesthetized adult cats. The ventilatory response was observed in conscious animals intact, after carotid denervation (CD), and after midcollicular decerebration. The results show that the initial small ventilatory depression was unaffected by CD but that the subsequent characteristic tachypnea was blunted after CD even after more prolonged exposure to CO. The CO tachypnea was not observed after decerebration, but a residual hyperventilation was noted with the higher concentration used. It may be concluded that carotid chemoreceptors do not mediate the CO tachypnea, which may then originate in suprapontine structures as shown by comparison of intact and decerebrate animals. The blunting of the tachypnea after CD may be caused by the relative hypercapnia observed in CD animals. The residual hyperventilation observed in decerebrate animals may be caused by central acidosis and/or some peripheral potentiation of chemoreceptor activity resulting from the decrease in arterial blood pressure that accompanied CO inhalation in decerebrate animals. PMID- 2262466 TI - Role of dopamine and arterial chemoreceptors in thermal tachypnea in conscious cats. AB - In mammals submitted to a warm environment, intracerebral injection of dopamine (DA) produces no change or an increase in body temperature accompanied by an increase in metabolic heat production, but its effect on heat loss mechanisms such as vasodilation and tachypnea is not clear. Because the principal mechanism of heat loss in the conscious cat is thermal tachypnea, we studied the influence of DA on thermal tachypnea in response to heat stress (ambient temperature = 33 36 degrees C) in five conscious cats. We first studied the steady-state response to a DA agonist, apomorphine, which crosses the blood-brain barrier. Intravenous injection of apomorphine greatly reduced thermal tachypnea by decreasing respiratory frequency (from 94.9 to 52.5 breaths/min) and increasing tidal volume (from 13.2 to 20.4 ml). The subsequent injection of the DA antagonist haloperidol, which also crosses the blood-brain barrier, restored the initial tachypnea. To further investigate the mechanism involved in thermal tachypnea, we studied the influence of peripheral chemoreceptors by transiently stimulating or inhibiting carotid body (CB) activity during tachypneic breathing. CB stimulation by intravenous injection of NaCN or domperidone reduced thermal tachypnea mainly by decreasing the respiratory frequency, whereas CB inhibition by DA tended to increase frequency and thus tachypnea. It is concluded that 1) in a warm environment, central DA receptors are also greatly involved in heat loss mechanisms, 2) arterial chemoreceptor input appears to counteract this tachypneic breathing, and 3) thermal and hypoxic tachypnea may be controlled by the same mechanism in which a DA-like system has a key role. PMID- 2262467 TI - Ventilatory effect of acute pulmonary hypothermia. AB - The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs. The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling. Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied. Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG. Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths. There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9). When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4). In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume. The effect of cold bolus injection was eliminated after right vagotomy in three dogs. Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE. PMID- 2262468 TI - Hormonal and growth factor responses to heavy resistance exercise protocols. AB - To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release. PMID- 2262469 TI - Long-term effects of physical training on aerobic capacity: controlled study of former elite athletes. AB - We studied 15-yr changes in physical training, subcutaneous fat, and maximal oxygen consumption (VO2 max) in male former elite athletes (27 long-distance runners and 9 bobsledders) and in a control group of 23 normal men. In 1973, elite athletes all trained vigorously, whereas in 1988 there was a great interindividual variation in physical training. In the lowest tertile of runners' training activity in 1988 (n = 9), the rate of decline in VO2max during the 15 yr was 1.11 +/- 0.15 (SE) ml.kg-1.min-1.yr-1, or 16% per decade, whereas the most active quintile of runners (n = 5) tended to increase VO2max (NS). The remaining 13 runners showed a rate of decline in VO2max of 0.54 +/- 0.14 ml.kg-1.min-1.yr 1, or 7% per decade. The rates of decline were 0.22 +/- 0.12 and 0.56 +/- 0.10 ml.kg-1.min-1.yr-1, or 5 and 11% per decade, in bobsledders and controls, respectively. When normalized for lean body mass instead of body weight, VO2max showed a reduced variability in the rate of decline, with values ranging from 0.00 +/- 0.27 (most active runners) to 0.69 +/- 0.15 ml.kg lean body mass-1.min 1.yr-1 (least active runners). In multiple linear regression analysis, 15-yr changes in mileage, running pace, and truncal fat together explained 51% of variance in the 15-yr change of VO2max normalized for body weight in runners and 41% in all study men. In runners, change in truncal fat was dependent on changes in both mileage and running pace. In the presence of physical training and anthropometric variables in the regression equation, the 15-yr decrease in maximum heart rate was only modestly predictive of the change in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262470 TI - Effects of ligation and embolization on Kf and multiple tracer measurements in dog lungs. AB - In isolated blood-perfused dog lungs, the capillary filtration coefficient (Kf) and the permeability-surface area product of urea (PS) were measured to determine their responses to two different methods of altering filtration area: lobe ligation (LL, n = 5) and glass bead embolization (GBE, n = 4) during constant perfusion rates (700 +/- 45 ml/min). When two of three lobes were ligated, Kf decreased (1.36 +/- 0.13 to 0.58 +/- 0.23 g.min-1.cmH2O-1; P less than 0.05), but PS did not change (2.02 +/- 0.4 to 1.71 +/- 0.3 ml/s). Kf per gram of perfused blood-free dry lung weight was unchanged by LL (0.051 +/- 0.17 to 0.052 +/- 0.18 g.min-1.cmH2O-1), indicating that surface area per gram measured by Kf remained the same. However, PS per gram dry lung doubled (0.07 +/- 0.016 to 0.146 +/- 0.06 ml/s; P less than 0.05) after LL, suggesting that recruitment occurred in the remaining lobe. When three lobes were embolized with 200-microns glass beads (0.48 +/- 0.01 g beads/kg body wt), PS decreased (2.1 +/- 0.22 to 0.94 +/- 0.09 ml/s; P less than 0.05), but Kf was not altered (1.01 +/- 0.17 to 1.04 +/- 0.18 g.min-1.cmH2O-1). The constancy of Kf after GBE implies that the vascular pressure increase during the Kf measurement was transmitted to both blocked and flowing vessels and thereby measured the same filtration area before and after GBE. PS decreased significantly after GBE because of a loss of perfused surface area by the beads blocking flow in small arterial vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262472 TI - Maximal exercise capacity and oxygen consumption of lambs with an aortopulmonary left-to-right shunt. AB - We determined maximal exercise capacity and measured hemodynamics in 10 6-wk-old lambs with an aortopulmonary left-to-right shunt [S, 57 +/- 11%, (SD)] and in 9 control lambs (C) during a graded treadmill test 8 days after surgery. Maximal exercise capacity (3.7 +/- 0.2 km/h and 10 +/- 5% inclination vs. 4.0 +/- 0.9 km/h and 15 +/- 0% inclination, P less than 0.02) and peak oxygen consumption (25 +/- 7 vs. 34 +/- 8 ml O2.min-1.kg-1, P less than 0.02) were both lower in the shunt than in the control lambs. This was due to a lower maximal systemic blood flow in the shunt lambs (271 +/- 38 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.01). Despite their high maximal left ventricular output, which was higher than in the control lambs (448 +/- 87 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.05), the left-to-right shunt could not be compensated for during maximal exercise because of a decreased reserve in heart rate (S: 183 +/- 22 to 277 +/- 38 beats/min; C: 136 +/- 25 to 287 +/- 29 beats/min) and in left ventricular stroke volume (S: 1.8 +/- 0.3 to 1.6 +/- 0.4 ml/kg; C: 1.0 +/- 0.3 to 1.3 +/- 0.2 ml/kg). We conclude that exercise capacity of shunt lambs is lower than that of control lambs, despite a good left ventricular performance, because a part of the reserves for increasing the left ventricular output is already utilized at rest. PMID- 2262471 TI - Decreased free fraction of thyroid hormones after prolonged Antarctic residence. AB - We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported "polar T3 syndrome." PMID- 2262473 TI - Effect of acute hypercapnia on limb muscle contractility in humans. AB - The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP. PMID- 2262474 TI - Biophysical properties of hypoglossal neurons in vitro: intracellular studies in adult and neonatal rats. AB - A brain stem slice preparation from adult and neonatal (less than or equal to 12 days old) rats and intracellular recordings were used to examine the cellular properties of neurons within the hypoglossal (HYP) nucleus. Resting membrane potential (Vm) for adult hypoglossal neurons was -80 +/- 2 (SE) mV. Rheobase was 2.1 +/- 0.4 nA, and input resistance (RN) was 20.8 +/- 1.5 M omega and decreased during the hyperpolarizing period ("sag"). Compared with adult HYP cells, newborn HYP neurons had significantly lower resting potentials (Vm = -73 +/- 2 mV), lower rheobase (0.7 +/- 0.2 nA), and higher RN (27.6 +/- 3.9 M omega). Single action potentials, elicited by short depolarizing-current pulses, were followed by a slow afterhyperpolarization in adult [6.4 +/- 0.3 mV, time constant (tc) 31.0 +/- 1.2 ms] and newborn cells (7.4 +/- 0.2 mV, tc 37.2 +/- 8.2 ms). Prolonged outward current (2 s) produced little spike frequency adaptation in either adult or newborn neurons. Onset of spike activity was not delayed by hyperpolarizing pulses preceding depolarizations. In addition, pharmacological experiments showed that HYP neurons have a tetrodotoxin-sensitive Na+ current and a delayed and an inward rectifier current but no major Ca2+ current. We conclude the following. 1) Electrophysiological membrane properties mature postnatally in HYP neurons; some of these developmental changes can be ascribed to an increase in soma size and dendritic outgrowth but others cannot. 2) Adult HYP neurons, compared with other brain stem neurons (i.e., vagal cells or cells in the nucleus tractus solitarius), are not endowed with major Ca2+ currents or K+ currents such as the A current and the Ca2(+)-activated K+ current. PMID- 2262475 TI - Fluid balance in sheep lungs before and after extracorporeal perfusion. AB - Lung fluid balance was studied in sheep under the following conditions: 1) unanesthetized, standing in a metabolic cage; 2) anesthetized, in a supine position; 3) 1 h after extracorporeal perfusion; and 4) either 4-6 h after extracorporeal perfusion (i.e., control experiments) or 1.5 h after left atrial pressure was increased by 15 cmH2O. Lung lymph flow rate (QL), plasma and lymph concentrations for nine protein fractions, urea permeability-surface area product (PS), urea effective diffusivity (D1/2S), and extravascular lung water (VE) were measured under each condition. Bloodless wet and dry lung weights were measured at the end of each experiment. QL increased and lymph-to-plasma concentration ratio for total proteins (L/P) decreased after the sheep were anesthetized and placed in a supine position. This possibly resulted from an increase in microvascular pressure induced by anesthesia and/or reorientation of the lungs. PS, D1/2S, and VE decreased, indicating a decrease in perfused surface area associated with a decreased cardiac output or alteration in lung orientation. After 90 min of extracorporeal perfusion, no significant differences were found in QL, PS, and D1/2S compared with those measured during the anesthetized period. No changes in PS or D1/2S could be detected after an average of 4.2 h of extracorporeal perfusion. The average bloodless wet-to-dry lung weight ratio [(W D)/D] was 3.77 +/- 0.12, well within the range for normal sheep lungs. An increase in venous pressure of 15 cmH2O produced a response similar to that observed in the unanesthetized sheep lung lymph preparation: QL increased, L/P decreased, PS and D1/2S did not increase, and VE and (W-D)/D increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262476 TI - Vagal cholinergic innervation of the airways in newborn cat and dog. AB - Although several studies have examined the pulmonary response to muscarinic agonists in the newborn, none has addressed the functional capabilities or "maturity" of vagal innervation to airway smooth muscle in the newborn. The purpose of the present study was to provide a quantitative analysis of the ability of vagal excitatory innervation (encompassing the pre- and postganglionic fibers, airway ganglia, and airway smooth muscle) to alter pulmonary mechanics in the newborn. We measured the changes in pulmonary mechanics elicited by electrical stimulation of the vagus nerves in 20 newborn cats and 18 puppies anesthetized with chloralose urethan. Animals were tracheotomized and ventilated (chest open), and the cervical vagus nerves were sectioned and placed on stimulating electrodes. Animals were placed in a flow plethysmograph, and mean inspiratory resistance (RL,I) and dynamic compliance were measured on a breath-by breath basis. In each animal RL,I increased, dynamic compliance decreased, and heart rate slowed during 10 s of vagal stimulation at frequencies ranging from 2 to 20 pulses/s. At each stimulus frequency there was a spectrum of responses with respect to the percent change in RL,I. At 15 pulses/s there was a fourfold difference in the RL,I response of the most- and least-sensitive animals. In both species, higher stimulus frequencies caused greater increases in RL,I; at 2 pulses/s RL,I increased on average approximately 40%, compared with approximately 250% at 20 pulses/s. The increase in RL,I was similar in the kitten and puppy at stimulus frequencies of 6 and 15 pulses/s but was less in the kitten at 2 pulses/s (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262477 TI - Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen. AB - Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux. PMID- 2262478 TI - Exponential fitting of pressure-volume curves: confidence limits and sensitivity to noise. AB - It has recently become common to model the static pressure-volume curve of the lung as a monoexponential function of the form V = A - Be-KP, where V is volume and P is transpulmonary pressure. The parameters A, B, and particularly K have been employed as descriptors of the intrinsic mechanical properties of the lung. The purpose of the present study was to investigate the sensitivities of A, B, and K to noise in measurements of P and V and to incompleteness of data. Using Monte-Carlo simulation, we found that the presence of typical levels of noise in P led to biased estimates of K and that the 95% confidence intervals about A and K were large compared with the parameter values themselves. These effects were increased as points were systematically removed from either end of the data set. These findings show that values of K estimated from PV data are difficult to interpret without accompanying confidence intervals. PMID- 2262479 TI - A very low dead space pneumotachograph for ventilatory measurements in newborns. AB - In premature and full-term neonates, technical limitations hamper the measurements of pulmonary mechanics. Current commercially available pneumotachographs (PNT) either increase the dead space, causing hyperventilation, or increase resistance, thus altering the mechanics of breathing. We modified a previously described low dead space PNT for infants to increase the linear range and frequency response. The mean resistance of the new PNT was 2.44 cmH2O.1-1.s compared with 2.65 cmH2O.1-1.s for the Fleisch no. 0 PNT. The added dead space over the standard endotracheal connector was 0.6 ml compared with 4.7 ml for the Fleisch PNT. Like the Fleisch PNT, the flow resistance was linear from 0 to 15 l/min. In response to a sinusoidal waveform, the new PNT had a phase angle of 21 degrees at 5 Hz and 50 degrees at 16 Hz compared with 19 degrees and 43 degrees, respectively, for the Fleisch PNT. The change in attenuation for both systems was zero until 20 Hz. In summary, the new PNT is lightweight and provides accuracy and low resistance with a very small dead space. PMID- 2262480 TI - The acoustocardiogram: a noninvasive method for measuring heart rate of avian embryos in ovo. AB - A method is presented for measuring the heart rate of avian eggs noninvasively during the last half of incubation. The technique involves briefly placing an egg in tightly sealed vessel containing an inexpensive condenser microphone. The amplified output of the microphone, termed the acoustocardiogram (ACG), is nearly sinusoidal in shape and synchronous with the electrocardiogram. The ACG can also be obtained by mounting the microphone directly on the shell with Plasticine. The method offers advantages over previously described techniques in simplicity, low cost, and noninvasiveness. PMID- 2262481 TI - Gas exchange across avian eggshells oscillates in phase with heartbeat. AB - Rahn et al. (J. Appl. Physiol. 69: 1546-1548, 1990) showed that the gas pressure in a plethysmograph containing an intact egg oscillates in phase with electrocardiogram (ECG) and that this pressure variation could be used as a noninvasive way to determine the heart rate of an avian embryo. One possible mechanism to account for the pressure oscillation is the mechanical movement of the embryonic heart, which leads to volume shifts of gas within the plethysmograph. Another possibility is that the oscillation of gas pressure with heartbeat is pulsatile gas exchange resulting from pulsatile blood flow. If gas exchange were transiently stopped, a pressure signal dependent on gas exchange should disappear, while a pressure signal dependent on cardiovascular motion should persist. Using a number of late-age hen eggs (at days 15-20 of incubation), we tested these hypotheses by suddenly changing the gas composition surrounding an egg and measuring the effect of the pressure oscillation. We found that 1) after 5% CO2-95% N2 was flushed into the plethysmograph (presumably halting gas exchange), pressure oscillations went almost to zero and the ECG signal remained; after air was flushed back to the plethysmograph, the pressure signal returned to control level; 2) after 20% CO2-20% O2-60% N2 was flushed into the plethysmograph (presumably increasing net gas exchange), the pressure signal increased 2.5-fold compared with that in air; and 3) after 1% CO2-99% N2 was flushed into the plethysmograph (presumably reversing gas exchange), the oscillation pressure decreased to one-fourth of that in air and the phase of pressure relative to ECG reversed compared with the phase in air.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262482 TI - Directions for future research in childhood lymphoblastic leukemia. AB - Progress in therapy of acute lymphoblastic leukemia continues at a steady pace, with event-free survival rates approaching 90% for low-risk and standard-risk patients. The challenge now is to use the emerging new insights into the unique biology of the leukemic lymphoblast to create novel strategies for curing ALL with minimum toxicity. It is hoped by all of us that these volumes help to stimulate development of new approaches to curing ALL at the lowest possible cost to the patient and to society. PMID- 2262483 TI - Pharmacology and drug resistance in childhood lymphoblastic leukemia. AB - In the first part of this article, the pharmacology of the chemotherapeutic agents used in the treatment of childhood lymphoblastic leukemia is reviewed, detailing their mechanisms of action, pharmacokinetics, and toxicities. A section on central nervous system pharmacology discusses advances made in the treatment of meningeal leukemia. Mechanisms of drug resistance are discussed in the second section of the article, outlining the biochemical basis for and clinical implications of both agent-specific resistance and multidrug resistance. PMID- 2262484 TI - Detection of minimal residual leukemia in acute lymphoblastic leukemia. AB - Morphologic, immunologic, enzymatic and cytogenetic methods detect residual leukemic cells at the level of 5%. The early detection of leukemia by these methods has failed to improve outcome for children with residual disease. The use of molecular biologic techniques, particularly those involving the polymerase chain reaction, can detect 1 leukemic cell among 10,000 or even 100,000 normal cells. At this time, it is essential to conduct the proper clinical trials to determine the clinical utility of methods so sensitive and specific. PMID- 2262485 TI - Primary treatment of childhood acute lymphoblastic leukemia of non-T cell lineage (including infants). AB - About 85% of children with ALL have leukemic blasts that express cell membrane antigens associated with B-cell lineage, although few are surface immunoglobulin positive. Patients differ from children with ALL of T-cell lineage in that they tend to be younger, less predominantly male, and less likely to have a mediastinal mass or CNS leukemia at diagnosis, and they have a lower leukocyte count. Leukemic blasts from these children are more likely to be hyperdiploid. However, B cell-lineage ALL is not homogeneous either. It includes infants, children, and adolescents; it includes patients with leukemic blasts that either express or fail to express CD10, CD24, and cytoplasmic immunoglobulin. B cell lineage ALL includes patients with blasts showing hyperdiploidy and patients with blasts with translocations such as t(4;11), t(1;19), and t(9;22). In general, outcome for patients with B cell-lineage ALL is superior to the outcome of those with T cell-lineage ALL in univariate analysis. However, when comparisons are stratified by age and leukocyte count, any apparent prognostic advantage for children with B cell-lineage ALL is diminished. The addition of effective CNS prophylaxis to effective systemic chemotherapy made cure a reality for about one half of children with ALL. Subsequent work has made it possible to omit cranial irradiation and its sequelae for most children with ALL. At least three regimens have offered an unambiguous improvement over the original St. Jude prophylactic CNS therapy regimen. These regimens are the BFM 76/79 regimen, the New York regimen, and the Dana-Farber regimen. Cure appears possible for 70% of children. These regimens differ markedly in detail, but appear to benefit similar subsets of patients. Identification of their critical therapeutic elements is one challenge for the future. A second challenge is the early identification of patients likely to do poorly on these effective regimens, whether by age under 1 year, specific blast morphology, cytochemical findings, immunophenotype, cytogenetic findings, drug pharmacokinetic features, or early response to antileukemic therapy. The third challenge is continued awareness of the acute morbidity of therapy and its impact on the lives of children and their families, together with a heightened vigilance for likely long-term sequelae. Most children with lymphoblastic leukemia in the United States are referred to cancer treatment centers for the initiation of therapy. Over one half of the children who are diagnosed participate in formal clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2262486 TI - Treatment of T-lineage acute lymphoblastic leukemia. AB - T-cell acute lymphoblastic leukemia is an aggressive disease that responds poorly to "standard" therapy designed for the more common B-lineage ALLs in childhood. The principles of this "standard" therapy were derived from empiric clinical trials. Thus, it is not surprising that the therapy that had the greatest impact on survival in the group as a whole would be found to be most successful for the most common subset of patients. T-cell malignant lymphoblasts share many biologic features that set them apart from the more common B-lineage lymphoblasts. Some of these biologic features suggest therapeutic approaches that should be particularly successful in treating patients with T-cell leukemia. The use of aggressive, multiple-agent "pulse" chemotherapy has been shown through empiric trials to have relative efficacy in T-cell lymphoblastic leukemia, presumably because of the rapid generation time and high growth fraction. Future studies will (1) determine the optimal dose and schedule of cytosine arabinoside needed to exploit the increased Ara-CTP accumulation in T-cell blasts, (2) determine the efficacy of a new agent, deoxycoformycin, an inhibitor of adenosine deaminase, to exploit the biochemical phenotype of T-cell blasts, and (3) assess the ability of conjugated anti-T monoclonal antibodies to deliver a cytotoxic agent, thus exploiting unique antigenic determinants at the cell surface. As more is learned about the biology of T-cell malignancies, further treatment strategies may be suggested to exploit the new features that are discovered. Similarly, it is hoped that the unique features of the B-lineage leukemias will suggest treatment strategies that will improve survival in those patients as well. Certainly, improved survival has already been achieved in the case of the B-cell leukemias and Burkitt's lymphomas, and improvement may also be possible for the pre-B and early pre-B phenotypes of lymphoblastic leukemia. PMID- 2262487 TI - Prevention of meningeal leukemia. Review of 20 years of research and current recommendations. AB - By use of prophylactic CNS therapy, the incidence of meningeal relapse has been dramatically reduced and the length of the initial bone marrow remission has been greatly prolonged in children with acute lymphoblastic leukemia. Pinkel performed a controlled study in which 94 patients were randomized to one of two regimens of presymptomatic CNS therapy, or received no prophylactic CNS therapy. This crucial study showed that prophylactic CNS therapy was very useful both in preventing meningeal relapse and in prolonging the duration of complete remission. Then, many additional regimens for prophylactic CNS therapy were tried on thousands of children worldwide in an effort to improve upon these results. Among the many CNS therapy regimens that were tried, none gave results better than the original St. Jude regimen. Our knowledge of CNS leukemia in general has greatly increased, but the last 20 years have brought us no further significant progress as to improved results in preventing meningeal leukemia. The many novel and innovative CNS therapy regimens that have been tried have yielded essentially the same results as to prevention of meningeal leukemia and as to duration of disease-free survival. Five to ten percent, or fewer in patients at low risk, still show meningeal relapse, and nearly one half of children with ALL still have hematologic relapse within the first 5 years following initiation of therapy. The goal now is to reduce neurotoxicity. Thus, progress has been stymied and we now await some new addition to therapy that will dramatically improve our results. Nonetheless, there are still many promising avenues of research yet to be explored. Meningeal leukemia remains a fascinating and satisfying field of clinical research. PMID- 2262488 TI - Diagnosis and management of relapse in acute lymphoblastic leukemia. AB - Although the results are steadily improving, the treatment of the child with lymphoblastic leukemia in relapse remains unsatisfactory. Owing to the very nature of relapse, it is highly unlikely that future chemotherapy protocols will provide curative treatment for the majority of patients with recurrent disease. Therefore, the greatest possible emphasis must be given to further improvements and refinements in front-line (initial) therapy so as to prevent relapse from ever occurring. Our goal should be to put the relapse leukemia specialist "out of business." PMID- 2262489 TI - Role of bone marrow transplantation in childhood lymphoblastic leukemia. AB - Allogeneic bone marrow transplantation is the only therapy introduced in the past 2 decades that has offered a better prognosis for children with ALL who have suffered a marrow relapse within 18 months of starting therapy. Currently, 40 to 50% of such patients are obtaining long remissions and are potentially cured by marrow transplantation. This therapy's effectiveness, however, is diminished by the problems of acute and chronic graft-versus-host disease, infection, and relapse. Further impact of marrow transplantation in the treatment of ALL awaits (1) more effective antileukemic preparative regimens or post-transplant antileukemic strategies, (2) less toxic preparative regimens to decrease the incidence of early and late effects, (3) more effective means of preventing and treating graft-versus-host disease, (4) the ability to safely perform mismatched marrow transplantation, and (5) more effective means of purging leukemic cells from remission bone marrow to expand the role of autologous marrow transplantation. PMID- 2262490 TI - Paradoxical embolism: an underestimated entity. A plea for comprehensive work-up. AB - Forty-one cases of arterial embolism were reviewed. The work-up included M + 2D echocardiography in 29 patients (71%), arteriography in 22 (54%), both echocardiography and arteriography in 19 (46%), and abdominal aortic ultrasound in 18 (43%). The sources of emboli were probable cardiac (8 = 20%)--mural cardiac thrombus detected by echocardiogram; possible cardiac (12 = 29%)--arrhythmias or other cardiac pathology detected without mural thrombus; probable arterio arterial (7 = 17%)--proximal arterial thrombus detected; probable paradoxical embolism (2 = 5%)--fulfills the Johnson criteria with cardiac defect and right-to left shunt detected by contrast echo in one patient and cardiac catheterization in the other; possible paradoxical embolism (3 = 7%)--meets two of three Johnson criteria without evidence of other source; and unknown source (9 = 22%)- conventional work-up negative or incomplete. Five of nine patients (56%) less than 50 years old had probable or possible paradoxical embolism, while in two patients (22%), the origin was unknown. CONCLUSION: (1) A significant proportion of patients with an arterial embolus are discharged with the source of emboli unknown, (2) paradoxical embolism must be considered and contrast saline or transesophageal echocardiogram should be done in patients under 50 years old. PMID- 2262491 TI - The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex. AB - The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free. PMID- 2262492 TI - Large diameter expanded polytetrafluoroethylene grafts for infrarenal aortic aneurysm surgery. AB - The performance of an expanded polytetrafluoroethylene (ePTFE) graft used for aortic aneurysm replacement was evaluated. ePTFE grafts were implanted in 241 patients undergoing infrarenal abdominal aortic aneurysm (AAA) repair. Sixty patients were operated as emergencies for aneurysm rupture and 181 electively. One hundred and fourteen bifurcated and 127 tube grafts were inserted. The transperitoneal approach was used in 64 cases and the remainder were placed using a retroperitoneal approach. There was a one-month mortality of 2.8% in elective and 20% in emergency cases. Median follow-up was 26 months. Specific graft complications included one infected graft resulting in a graft-enteric fistula. No graft rupture, degeneration, dilatation, pseudoaneurysm or late graft limb thromboses were observed in up to 7 years of follow-up. The aortic ePTFE prosthesis demonstrated satisfactory performance over the period studied. PMID- 2262493 TI - Splenorenal arterial shunt in the treatment of renovascular hypertension. Approach by a lumbar-retroperitoneal incision. AB - In a period of 16 years, 29 consecutive patients were operated on for a splenorenal arterial shunt through a lumbotomy incision and a retroperitoneal approach. There were 18 males and 11 females with a medium age of 42 years. All cases had uncontrollable and severe hypertension for an average medium time of 48 months, 11 patients had variable degrees of renal insufficiency. The diagnosis was made utilizing standard methods including in all cases angiography of the abdominal aorta, celiac axis and renal arteries. One patient died after the operation due to intestinal infarction, the remaining have been followed for a medium time of 50 months. All patients improved or cured their renal insufficiency. The hypertension was cured in 23, improved in 4 and failed in 1, this latter patient was successfully autotransplanted. A precise exposition of the surgical technique is presented with comments about their advantages and indications. A review of the literature in surgical experience with the technique of splenorenal arterial anastomosis has been done. PMID- 2262494 TI - The validity of canine platelet aggregometry in predicting vascular graft patency. AB - Several laboratories have found canine platelet aggregometry predictive of thrombotic potential in vascular grafts. Adenosine diphosphate (ADP) is a frequently used agonist, often at unspecified or differing concentrations. This study was designed to evaluate the predictive value of ADP-induced platelet aggregometry and the validity of the methodology. Platelet aggregometry in response to 2 x 10(-5) M ADP was assayed in 70 dogs. Twenty-six percent were aggregators, 51% were non-aggregators, and 20% were indeterminant. All dogs were then treated with aspirin and dipyridamole. Vascular prostheses were implanted bilaterally (aorto-iliac) and anti-platelet therapy continued for two weeks. Dose response to ADP was studied at three concentrations in 20 dogs. At 2 x 10(-5) 1/20 aggregated, at 4 x 10(-5) 3/19 aggregated and at 2 x 10(-4) 15/20 aggregated. Time between samples and study was evaluated in 11 dogs, with 2/11 changing from non-aggregator to aggregator at two or three hours. Daily reproducibility was studied in 70 dogs, 14 of which changed aggregation status between days. Patency was 58/68 (85%) for non-aggregators, 23/34 (68%) for aggregators (p = 0.038). Platelet aggregometry has significant predictive value for graft patency but methodology must be specified and standardized. PMID- 2262495 TI - Ultrastructural evidence of the effects of shear stress variation on intimal thickening in dogs with arterially transplanted autologous vein grafts. AB - Based on our findings that changes in wall shear stress, not the rate of blood flow, were the main hemodynamic factor related to intimal hyperplasia of autologous vein grafts, we further investigated the effect of wall shear stress variation on sequential ultrastructural changes in the intimal hyperplasia of arterially transplanted autovein grafts, using canine models. As noted, wall shear stress variation (tau-variation) could be defined by the variation in wall shear stress within a cardiac cycle, using a desktop flow waveform analyzer. In Group I, which had a high flow rate of 78.4 +/- 4.6 ml/min and low tau-variation of 36.1 +/- 2.2 dynes/cm2, intimal hyperplasia was significant. Ultrastructurally, there was a marked transformation of intimal smooth muscle cells to secretory cells 2 to 4 weeks after implantation. The surface of the intima was lined with modified smooth muscle cells at 2 weeks after implantation. In Group II, which had a low flow rate of 5.6 +/- 2.2 ml/min and normal tau variation value (174.6 +/- 13.0 dynes/cm2), intimal hyperplasia was minimal, and there were several layers of contractile type smooth muscle cells, with characteristic myofibrillae. The surface of the intima was lined with endothelial cells at 2 weeks after implantation. These findings suggest that, in regions of low wall shear stress variation, intimal smooth muscle cells of autovein grafts may well become secretory cells, and enhanced platelet adherence could occur during early intimal repair, causing intimal hyperplasia to develop. PMID- 2262496 TI - Pseudoaneurysm: diagnosis with color Doppler ultrasound. AB - Increasing numbers of interventional radiologic procedures, often with large arterial catheters, have led to increasing total numbers of complications. Pseudoaneurysm is not an infrequent complication. It is often difficult to differentiate pseudoaneurysm clinically from hematoma. In the past, we have used gray scale duplex scanning to aid in this differentiation. We have recently found color Doppler scanning to allow quicker, easier, and more accurate diagnosis. Color Doppler imaging also can often demonstrate the track between the artery and the aneurysm. PMID- 2262497 TI - Superficial femoral artery as inflow for bypass to the proximal popliteal artery. AB - We have obtained long term follow-up on 58 patients in whom the superficial femoral artery was used as a donor site for bypass to the proximal popliteal artery. The indication for the reconstructive procedure was intermittent claudication 36%, rest pain 34%, and gangrene 26%. All patients had angiographic evidence of a patent proximal superficial femoral artery and many had relative indications for short bypass such as limited saphenous vein availability or compromised medical condition. There was a cumulative patency rate of 79% by life table method for the series with a six year follow-up. We have observed that the superficial femoral artery is a satisfactory inflow site for proximal popliteal bypass grafts in selected patients. The procedure can maximize use of a limited segment of vein with minimal operative time and morbidity. Inflow stenosis can be revised or long bypass procedures can be offered in the event of graft failure. PMID- 2262498 TI - Crural artery bypass with adjunctive arteriovenous fistula. A modification in distal anastomosis. AB - We carried out crural artery bypass with an adjunctive arteriovenous fistula in 8 lower extremities of 7 patients with severe ischemic symptoms and poor distal run off. Mean blood flow rates in the implanted grafts ranged from 43 to 340 ml/min and those of the reconstructed crural arteries from 20 to 100 ml/min. A stenotic lesion was noted on postoperative angiogram in one patient and stasis symptoms caused by downward blood flow into the distal veins in another. The other patients have remained well with good function of the grafts 1-5 years after surgery. We modified the distal corner of the anastomosis as follows: three additional interrupted simple sutures were made on the anterior wall of the concomitant arteriotomy and venotomy incisions after making the common posterior wall of the vessel incisions. A vascular pocket formed at the distal corner of the anastomosis prevents stricture at the anastomosis. The vein is finally ligated just distal to the fistula to intercept downward blood flow into the distal veins. This modification in technique is recommended to prevent stricture of the distal anastomosis and postoperative stasis symptoms. PMID- 2262499 TI - Clip repair of peripheral side-to-side arteriovenous fistulas. Evaluation of a method in dogs and preliminary results in humans. AB - A simple technique for repair of peripheral arteriovenous fistula by clip application is presented. This procedure is rapid and effective, it minimizes the extent of dissection, and it eliminates the need for application of vascular clamps on the vessels and for anticoagulation. The safety of the procedure was confirmed in dog experiments and clinically applied successfully in four patients. It is suitable for simple, uncomplicated side-to-side fistulas amenable to this procedure. PMID- 2262500 TI - Venous dysfunction of late pregnancy persists after delivery. AB - Pregnancy is associated with DVT, pelvic thrombophlebitis, and lower extremity varicosities. Pelvic venous compression by the gravid uterus is blamed. A prospective controlled study using plethysmography was performed. Venous capacitance and outflow were measured at term, and at 1 week, 6 weeks and 3 months following delivery. Results show decreased venous capacitance and venous outflow at term pregnancy, no improvement 1 week after delivery, modest improvement at 6 weeks, and dramatic statistically significant improvement in both parameters by 3 months. The persistence of venous dysfunction for several weeks after delivery indicates that changes in venous function at term pregnancy are largely the result of factors other than pelvic venous compression by the gravid uterus. PMID- 2262502 TI - Campylobacter fetus infection of abdominal aortic aneurysm. AB - A 61-year-old man with Campylobacter fetus infection of an abdominal aortic aneurysm treated surgically is presented herein, the fifth survival case reported in the literature. Fever and back pain preceded the enlargement of atherosclerotic abdominal aortic aneurysm. The patient tolerated satisfactorily total excision of the aneurysm followed by axillo-femoral prosthetic bypass. Antibiotic therapy consisted of intravenous infusion of fosfomycin and gentamicin and oral administration of minocycline. The organism cultured from the aneurysmal wall and intraluminal thrombi was identified as Campylobacter fetus from its typical characteristics. It is concluded that this organism should be considered in all cases of infected aneurysm in elderly or debilitated patients. PMID- 2262501 TI - A rare case of renovascular hypertension due to iatrogenic thoracoabdominal aortic dissection. A report of successful surgical treatment in childhood. AB - Renovascular hypertension due to iatrogenic thoracoabdominal aortic dissection in an 8-year-old girl with aortic valvular stenosis is presented. A splenorenal arterial anastomosis without splenectomy was successfully performed. This procedure is considered best suited for children with thoracoabdominal aortic dissection as the autogenous graft is expected to grow and provide long-term patency. The spleen left in situ was expected to be advantageous, from the immunological aspect, at the time of open heart surgery for aortic valvular stenosis, which was anticipated in the near future in this child. PMID- 2262503 TI - Parenteral illegal drug use and limb loss. AB - The problem of illegal drug abuse and extremity loss was identified in 27 patients-22 men and 5 women, with a mean age of 26 years. Associated medical problems included: smoking in 27, cardiac disease in 2, diabetes in 3, and hypertension in 3. Six femoral pseudoaneurysms, 2 with distal emboli and all with sepsis and thrombosis, directly contributed to limb loss along with 2 patients with progressive phlegmasia dolens. There were 3 below-the-elbow, 7 above-the knee, 11 below-the-knee, and 6 transmetatarsal amputations. Eight patients received prostheses; 8 patients subsequently died in follow-up. PMID- 2262504 TI - Femoral saphenous vein bypass in a newborn. AB - This is believed to be the youngest patient to undergo a saphenous vein bypass for iatrogenic trauma of the right superficial femoral artery. The infant had emergency right heart catheterisation and Rashkind septostomy for severe desaturation due to transposition of the great arteries. During the exposure of the saphenous vein, the superficial femoral artery was accidentally severed at it's origin. An attempt to restore the circulation by end-to-end anastomosis failed and resulted in persistent limb ischemia for over 4 hours. The baby was reoperated upon, the damaged part of the superficial femoral artery was resected and a saphenous vein graft interposed between the common and the distal superficial femoral artery. PMID- 2262505 TI - A denaturated venous homograft as an alternative material for shunts and other reconstructions in congenital cardiac surgery. AB - A human venous homograft "Varivas R", in clinical use for 10 years for vascular access loops and femoropopliteal bypasses, has been used since December 1985 as a material for aortopulmonary shunts and other reconstructive procedures in congenital heart surgery. For this purpose vein segments 5 cm length, varying in diameter from 4 up to 10 mm by steps of 1 mm, were obtained. Our experience with Varivas is limited to 59 patients. Of 47 infants, 18 received a left, and 25 a right sided aortopulmonary shunt, 9 had bilateral aortopulmonary shunts, 2 right ventricle pulmonary conduits, 1 a pulmonary-pulmonary conduit, 3 interrupted aortic arch reconstructions and 4 a central aortopulmonary shunt, 1 with confluence reconstruction, 3 recidives of coarctation a patch repair. Among 11 adults 6 received coronary bypass and 6 others vascular reconstructions. In contrast to other artificial graft materials, the vein material offers easy manipulation similar to the daily routine of handling fresh vein material offers easy manipulation similar to the daily routine of handling fresh vein grafts in coronary surgery. The appropriate diameter sizes match better the infants anatomy, without the risk of kinking and/or anastomosis displacement. Peroperatively it was possible to confirm patency by electromagnetic flow measurement and the postoperative examinations were done by colour Doppler echocardiography. We had to reoperate upon 4 infants because of early thrombosis; on 1 infant for stenosis of the graft and on another 5 for late thrombosis. In an attempt to extend the indications for "inoperable" pulmonary hypoplasia/atresia we were not able to keep the shunt open in 4 infants. PMID- 2262506 TI - Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method. AB - This study compared the results of annuloplastic repair of tricuspid regurgitation (TR) using Doppler echocardiography. Sixty-three patients who underwent tricuspid annuloplasty were studied. Thirty-four patients received Kay Boyd annuloplasty and 29 Carpentier-Edwards ring annuloplasty. A new classification of TR based on the direction and area of regurgitation flow on Doppler echocardiogram was applied preoperatively. In the Kay-Boyd group, 10 cases showed massive TR and 24 cases showed localized TR preoperatively. Localized TR was well controlled in all cases, but 8 of 9 cases of massive TR showed grade III residual TR. In the C-E group, 21 cases showed massive TR and 8 cases showed localized TR. All cases were well controlled postoperatively. We conclude that (1) although the Kay-Boyd method is acceptable for localized TR, the C-E method should be employed for massive TR; (2) analyzing the regurgitant pattern of TR by Doppler echocardiogram is useful in selecting an appropriate surgical technique. PMID- 2262507 TI - New quantitative method for evaluating tricuspid regurgitation. AB - A new quantitative method for evaluating regurgitation (TR) is proposed in order to select the most suitable treatment for functional TR associated with acquired valvular heart disease. The regurgitant volume per beat (VTR) is calculated using two-dimensional color Doppler and continuous-wave Doppler echocardiographies. In a study of 48 patients, preoperative VTR showed a significant correlation with tricuspid annular diameter at end-diastole, right atrial mean pressure and right ventricular end-diastolic pressure. Patients were classified into 3 groups according to preoperative VTR: Group I, VTR less than 10 cc (no. 18); Group II, VTR = 10-20 cc (no. 18); Group III, VTR greater than or equal to 20 cc (no. 12). This classification correlated well with the intraoperative findings of TR. In all Group I patients, VTR decreased without any tricuspid valve repair. In Group II, 17 of 18 patients underwent tricuspid annuloplasty, and showed a decrease in VTR to below 10 cc after surgery. In Group III, 10 underwent tricuspid annuloplasty and 2 tricuspid valve replacement. Three of the 10 with tricuspid annuloplasty showed a significant degree of postoperative VTR (10-20 cc). These 3 patients as well as the 2 with tricuspid valve replacement showed a preoperative peak-to-peak pressure difference across the tricuspid valve during the ejection phase (RVsp-TAv) of less than or equal to 20 mmHg and tricuspid annular diameter at end-diastole of greater than or equal to 50 mm. In conclusion, no tricuspid valve repair was required in Group I (TR I). For group II (TR II) patients, tricuspid annuloplasty was necessary and adequate for TR correction. For Group II (TR III) patients, a more substantial procedure like tricuspid valve replacement should be performed, especially when the preoperative RVsp-RAv is less than or equal to 20 mmHg and tricuspid annular diameter at end-diastole is greater than or equal to 50 mm. PMID- 2262508 TI - Repetitive intraoperative mapping and cryotherapy improve the results of endocardial resection for ventricular tachycardia. AB - Patients with recurrent ventricular tachycardia or a history of a sudden cardiac death episode and ventricular tachycardia inducible in the electrophysiology laboratory have a high incidence of recurrence and a high mortality despite medical therapy. Map-guided endocardial resection has improved treatment results, but is associated with a 10-30% failure rate. In our initial experience with endocardial resection (Group I) we incurred a 30% treatment failure rate. In the present study we have found the addition of sequential intraoperative mapping and routine use of cryotherapy (Group II) improved our results of ventricular tachycardia control without significant additional morbidity or mortality. PMID- 2262509 TI - Wound infection following early repeat sternotomy for postoperative bleeding. An experience utilizing intraoperative irrigation with povidone iodine. AB - A prospective observational study of median sternotomy wound infection was carried out in two consecutive groups of unselected patients undergoing early repeat sternotomy for postoperative haemorrhage. In Group A the pericardial cavity and sternotomy wound layers were irrigated with aqueous povidone iodine prior to repeat closure, while Group B did not receive povidone iodine. No median sternotomy infections were recorded in Group A compared to 5 cases in Group B (0 out of 22 vs 5 out of 21 patients, p less than 0.05). Amongst the patients with wound infection, three developed sternal dehiscence and mediastinitis with one death. The data suggests that povidone iodine irrigation may be effective in reducing wound infection in patients undergoing early repeat sternotomy after cardiac surgery. PMID- 2262510 TI - Surgical indication for aortic arch hypoplasia in infants. AB - To determine the surgical indications for aortic arch hypoplasia, the distal arch outer diameter, distal arch index (ratio of the distal arch diameter to the normal aortic ring diameter), and postoperative pressure gradient across the aortic arch were studied in 23 patients under 6 months of age who underwent surgery for coarctation and/or aortic arch hypoplasia. The ratio of the pressure gradient across the arch to the right radial artery was used to evaluate the postoperative level of stenosis. The maximum ratio of the pressure gradient that could be tolerated after surgery was considered to be 0.15 from the operative results. Negative correlations were found between the distal arch outer diameter and postoperative pressure gradient ratio (r = 0.80), and the distal arch index and postoperative pressure gradient ratio (r = 0.80). These correlations proved that in order to obtain a postoperative pressure gradient ratio of 0.15 or less, a distal arch outer diameter of 3.9 mm or more and a distal arch index of 0.63 or more were necessary. Consequently, a distal arch outer diameter of 3.9 mm or a distal arch index of 0.63 is considered to indicate that aortic arch hypoplasia is in need of repair. PMID- 2262511 TI - Anomalous origin of the left coronary artery from the pulmonary artery. Surgical alternatives depending of the age of the patient. AB - Four cases of anomalous origin of the left coronary artery from the pulmonary artery, three of which were operated upon in our Centre, are presented. An aortocoronary bypass with reversed autologous saphenous vein was carried out in both of the children; and in the adult, the anomalous ostium was closed from the interior of the pulmonary artery. After 84, 72, and 4 months of evolution, respectively, they were found to be asymptomatic, the mitral insufficiency had disappeared and the venous graft remained patent. In this paper, the clinical form of presentation, diagnostic possibilities and surgical treatment are analysed. PMID- 2262512 TI - Infective endocarditis and an embolomycotic aneurysm in a 25-month-old child. AB - Infective endocarditis in young children is uncommon, especially where there is no underlying structural heart disease. While septic embolization in adults occurs in up to 43% of the cases of endocarditis, there is little data on systemic embolization in cases of children. We present an unusual case of a 25 month-old child with infective endocarditis and an embolomycotic aneurysm treated by mitral valve replacement and aortoiliac reconstruction. PMID- 2262513 TI - Repair of coarctation with persistent fifth arterial arch and atresia of the fourth aortic arch. AB - Coarctation of the aorta with persistent fifth arterial arch and atresia of the fourth aortic arch between the left common carotid and left subclavian arteries was treated surgically in a two-month-old boy with transposition of the great arteries and double-outlet right ventricle. The aortic arch was repaired using side-to-side anastomosis of the left common carotid and left subclavian arteries, patch repair of the coarctated segment at the origin of the left subclavian artery, and ligation of the patent ductus arteriosus. Pulmonary arterial banding and balloon atrioseptostomy were performed for associated anomalies. PMID- 2262514 TI - The use of PTFE graft to correct anomalous drainage of persistent left superior vena cava. AB - A new technique to correct persistent left superior vena cava (LSVC) drainage into the left atrium is described in a 14-year-old patient with situs inversus, left atrial isomerism common atrium, and mitral valve regurgitation. During surgery, occlusion of the LSVC markedly increased the venous pressure, precluding its ligation. Because of the malposition of the heart and the unusual atrial anatomy, correction with an intra-atrial baffle was not attempted. After correcting the intra-cardiac anomaly, the LSVC was divided and anastomosed to the "right" atrial appendage using a segment of PTFE graft. The postoperative course was uneventful and an angiogram demonstrated excellent performance of the graft. PMID- 2262515 TI - [110 consecutive laparotomies for hepatic metastasis]. AB - From 1978 to 1988, we performed 110 laparotomies for hepatic metastases. With 41 resections for colorectal metastases, the survival was 34% at 3 years. The operative mortality was 7%. With 25 resections for non colorectal liver metastases, the survival was 42% at 1 year, 12% at 3 years. The results, compared with those of literature justify, in the absence of any other potential curative treatment, to remove colorectal liver metastases. For metastases from other tumours, results of resection for endocrine tumours and few sarcomas invite us to an aggressive approach. PMID- 2262516 TI - [Diagnosis and treatment of traumatic injuries of the duodenum and pancreas: 21 cases]. AB - Twenty one consecutive patients who sustained injuries to the duodenum or/and pancreas were admitted to our hospital over a ten year period. Sixteen blunt injuries and 5 penetrating injuries were encountered. Penetrating injuries were always suspected and treated by time; following blunt injury diagnostic delay was encountered in 7 patients and insufficient surgical procedure because of intraoperative misinterpretation in 2 patients. Most of the patients had associated intra-abdominal organ injuries. Adjuncts to diagnosis such as abdominal roentgenograms, serum amylase levels and gastroduodenography were not helpful. CT-Scan and ultrasound allowed to confirm the suspected diagnosis in 3 cases only. Intraoperative diagnosis was also challenging. Complete mobilization of the structures surrounding the duodenum and the pancreas to provide entire exposure was necessary. In 6 patients treated first in a peripheral hospital, diagnosis of the injury have been missed at first laparotomy and reoperation was necessary in all of them. Suture closure of the duodenum and drainage of the pancreatic region were the most common reparative technique used. More complicated procedures with pancreatic and/or duodenal resection were performed in 6 patients. Overall mortality in patients surviving more than 24 hours was 14% (suture line dehiscence after delayed operation and one death due to brain injury). PMID- 2262517 TI - [Thyroid function after thyroidectomy for benign goiter. 200 cases explored by ultrasensitive TSH]. AB - Based on a retrospective study of a series of 200 thyroidectomies for benign goitre and a mean follow up period of 12 Months, the authors analysed post operative thyroid function and correlated it with the degree of surgical excision (47 unilateral lobectomies, 91 classical subtotal bilateral lobectomies and 62 extended bilateral subtotal lobectomies). After a presentation of the results in comparison with data from the literature, the timing and threshold for the institution of replacement therapy are examined and the need for prolonged clinical and laboratory monitoring is also stressed. In terms of changes in laboratory criteria only monitoring of spontaneous changes in US TSH allows opotherapy to be avoided or conversely to accurately define the conditions for institution of definitive replacement therapy. The justification of total thyroidectomy in the treatment of multihetoronodular goitres almost totally involving the glandular parenchyma is acknowledged. PMID- 2262518 TI - [Subtotal gastric devascularization for hemorrhage caused by the rupture of gastric varices in cirrhotic patients]. AB - Hemorrhages caused by gastric varices are a real therapeutic problem in cirrhotic patients. We resort to gastric devascularization in such cases. In 5 of our patients, this devascularization was subtotal, preserving only the pyloric pedicle. Two patients died of liver failure, one immediately after the operation and the other during the second month. The other patients are still living and have not bled again after 9, 12 and 17 months, respectively. Three of the 5 operated patients presented with ischemia of the gastric mucosa postoperatively. In our opinion, the principle of gastric devascularization to an extent still to be defined seems to be an interesting way of treatment these hemorrhages, which are caused by the rupture of gastric varices due to overall portal hypertension. PMID- 2262519 TI - [Post-traumatic hemobilia caused by arteriobiliary fistula. A case report and review of the literature]. AB - One new case of post-traumatic hematobilia due to an arteriobilary fistula is reported. This etiology is relatively rare, and its diagnosis is sometimes difficult if the three signs: pain, bleeding and jaundice are not observed. The most effective paraclinical examination still is selective arteriogrpahy, which makes the diagnosis possible, accurately locates the fistula and sometimes allows hyperselective embolization, as it did in this case. The use of embolization for the treatment of post-traumatic hematobilia due to an arteriobiliary fistula reduces operative mortality for this disease, which still has a poor prognosis. PMID- 2262520 TI - [Mucinous cystadenocarcinoma of the appendix. A rare tumor of the right iliac fossa]. AB - An observation of a mucinous cystadenocarcinoma of the appendix, in the tumor form, revealed by a painful syndrome of the right iliac fossa in a 62-year man is reported. It is a rare malignant tumor as less than 0.5% of the appendicectomy parts present a malignant mucosecreting tumor. In our observation, the diagnosis was allowed by pre-operation imaging. An increase of the serous amount in the tumor markers (carcinoembryonic antigen) (CEA) and CA 19-9 was found before the intervention and the immunodetections performed on the operation part were positive for CEA and CA 19-9. The serous amounts of these markers were normalized after operation. To the author's knowledge, the interest of dosing the serous tumor markers in the observation of such a type of tumor is not mentioned in the literature. The recurrences are frequent and sometimes late even when the initial excision has been macroscopically satisfactory. A new increase of the serous amount of the markers could allow for an earlier detection of a recurrence during the patient follow-up. At present, the prognosis of these malignant forms remains very poor as the 5-year survival does not exceed 25%. PMID- 2262522 TI - [Vascular and nervous lesion and opening of the capsule in the last stage of dislocation of the elbow. A case report]. AB - The authors describes a case of posterior dislocation of the elbow in the extreme stage, associating total destruction of the capsule and ligaments, a total arterial lesion, elongation of the median nerve and the opening of the focus at Tscherne's stage III. This case allows considering the biomechanical aspects of dislocation of the elbow and updating the principles of its management. PMID- 2262521 TI - [Spontaneous rupture of the spleen disclosing pheochromocytoma]. AB - The authors report a case of spontaneous rupture of spleen inaugurating the symptomatology of a pheochromocytoma. After presenting the observation, clinical problems are considered with a deceptive abdominal symptomatology and myocardial ischemia that could be part of an "adrenergic myocarditis"; the mechanism of ruptured spleen is analyzed. The diagnosis approach is discussed through a reliability study of various explorations: computed tomography has a sensitivity ranging from 93 to 97% which approaches 100% when associated with magnetic resonance, methyl-iodo-benzyl-guanidine scanning seems to be provided with similar reliability. During checking up for pheochromocytoma spreading, ectopic location was not found, but a cold thyroid nodule was detected which allowed suspecting a SIPPLE syndrome. The three-stage surgical approach was required by symptomatology, hemostasis splenectomy, lateral pheochromocytoma excision after a short preparation by blocking alpha and beta, and then total thyroidectomy after extemporaneous confirmation of the existence of a medullary carcinoma of the thyroid. This pathologic association leading to a SIPPLE syndrome is listed as part of the multiple endocrine neoplasias of type II (MEN II). PMID- 2262523 TI - [Liver traumas]. AB - The high mortality rate in hepatic trauma is a concern for the surgeons on duty, who must know the physiopathological problems and the therapeutic solutions in order to make the decisions needed in view of both hepatic and extra-hepatic injuries according to the available means. The early vital risk is produced by 2 facts: injuries to the liver, in which bleeding account for the death in every second case, especially in case of vascular disinsertion in the caval suprahepatic junction, which fortunately occurs rarely; associated intra- or extra-abdominal injuries, which are unfortunately frequent, cause death in every second case of multiple trauma. On the basis of a series of 135 cases in our department and of a bibliographic study, this article is aimed at defining a strategy for treatment that will be adapted to the lesions, in order to try and improve the prognosis. With hemodynamically stable patients, a surgical watch and wait policy is possible under strict observation. Conservative surgery still has to play a dominant part. Hepatic resection is only rarely indicated, if absolutely necessary. Temporary tight packing for a few days, with early reoperation in a specialist department if required, is a logical approach in initially unfavorable circumstances. PMID- 2262524 TI - [Osteosynthesis of articular fractures of the heelbone using a reconstruction plate]. AB - The authors describe in detail this technique which employs a reconstruction plate which can be moulded in all directions. The plate, fashioned in a stereotyped way extemporaneously or even during the pre-operative period, perfectly fits the lateral surface of the calcaneus, curves behind the tuberosity and descends in front to the junction of the lateral and inferior surfaces of the greater apophysis. With its screws anchored in the sustentaculum tali, it supports the previously reduced thalamic body which is itself fixed to the sustentaculum by screws, thereby avoiding further slippage. The very solid union thus obtained allows early weight bearing. This technique allows logical treatment of all types of fractures. Numerous technical details provide surgical guidelines for these technically difficult fractures. The operating protocol may thus be used by all operators. There are plans to market a pre-moulded plate which would further simplify the procedure. Currently, 55 fractures have been treated by this technique. The median interval to weight bearing was 7 days and 6 weeks to walking without crutches (45 cases). The functional results in 34 cases with sufficient follow-up (16 Months) showed 71% satisfactory results (very good, good or quite good), 21% mediocre and 8% poor results. PMID- 2262525 TI - [Reduction of traumatic dislocation of the shoulder. For a gentler approach....]. AB - Early traumatic anterior dislocation of the shoulder may be reduced very easily using a method combining gentle traction along the axis of the arm, slow external rotation and outwards pressure on the humeral head with the patient seated. This gentle method does not require sedation or analgesia. PMID- 2262526 TI - [Ascites against ovary: a historic rarity]. PMID- 2262527 TI - [Cephalic duodeno-pancreatectomy for pancreatic metastasis of a malignant melanoma]. PMID- 2262528 TI - High-performance liquid chromatography of casein hydrolysates phosphorylated and dephosphorylated. I. Peptide mapping. AB - A mixture of small peptides of molecular weight averaging 1000 daltons, obtained by controlled hydrolysis of casein with proteases, chymotrypsin and trypsin, was separated by size-exclusion and reversed-phase high-performance liquid chromatography. Peptides were identified and located in the known casein structures from their amino acid content and their N- and C-terminal amino acid analyses. The primary structure of peptides identified from casein hydrolysate phosphorylated and casein hydrolysate dephosphorylated is presented. PMID- 2262529 TI - Rapid determination of clenbuterol residues in urine by high-performance liquid chromatography with on-line automated sample processing using immunoaffinity chromatography. AB - A liquid chromatographic column-switching system for automated sample pretreatment and determination of clenbuterol in calf urine, using an immunoaffinity precolumn with Sepharose-immobilized polyclonal antibodies against clenbuterol, is described. A second precolumn packed with C18-bonded silica was used for the reconcentration of desorbed clenbuterol prior to the analytical separation. Urine, after 2-fold dilution with buffer (pH 7.4), was loaded directly onto the immuno precolumn, where clenbuterol was trapped by the immobilized antibodies. This immuno precolumn has been used for more than 200 runs with standard solutions and samples. Bound analyte was desorbed with 0.01 M acetic acid and transferred, via the second precolumn, to the analytical column. The total runtime per sample was 35 min. Using a sample load of 27 ml of dilute urine and UV detection at 244 nm, the detection limit was 0.5 ng/ml. The mean recovery of clenbuterol added to a blank urine sample at the 5 ng/ml level was 82 +/- 2% (n = 5) as determined with standard solutions loaded onto the same system. Urine samples from treated animals were analysed and the clenbuterol concentrations were comparable to those obtained by high-performance liquid chromatography using solid-phase extraction for sample clean-up. PMID- 2262531 TI - Estimation of cyclosporin-A in whole blood by simple and rapid reversed-phase HPLC utilizing a salting-out extraction procedure. AB - Cyclosporin-A is a fungal cyclic undecapeptide immunosuppressive agent that is potentially active against proliferating T-lymphocytes and therefore helps the body to accept a transplanted organ. In this experiment, the drug is extracted from whole blood with acetonitrile. The extraction solvent (acetonitrile) is mixed with the whole blood at a 1:2 ratio on a vortex mixer and is centrifuged at 2000 x g. The supernatant is transferred into a fresh borosilicate culture test tube and 20 mg of zinc sulfate and 10 mg of cadmium sulfate (for 1.0 mL of whole blood) are added, vortex mixed, and centrifuged at 2000 x g. The supernatant is saturated with anhydrous ammonium sulfate and centrifuged, and salted-out acetonitrile from the aqueous mixture is injected into the HPLC system. A 60- x 4.6-mm 3-microns, slurry-packed ODS (C18) column is used with an isocratic elution of 66:2:32 (v/v), acetonitrile-isopropanol-water. The column temperature is maintained at 72 degrees C. Cyclosporin-A is detected by UV absorption at 205 nm and 0.10 to 0.002 AUFS. The limit of detection of the method is 15 ng/mL for a 100-microL injection volume, and the completion time for analysis of one sample is less than 15 min. Columns packed with different stationary phases and different dimensions are investigated to determine which column will give the maximum resolution, sensitivity, and selectivity. PMID- 2262530 TI - HPLC analysis of an amino bisphosphonate in pharmaceutical formulations using postcolumn derivatization and fluorescence detection. AB - Monosodium 4-amino-1-hydroxybutane-1, 1-diphosphonic acid (MK-217) is a bone resorption inhibitor implicated in the treatment of malignant hypercalcemia. This compound is very water soluble and has five ionizable groups with pKa values over the entire pH range. As a result, it is difficult to maintain a single species in solution for chromatographic separation. Since there is no chromophore in the molecular structure, UV detection is ineffective. The compound and its potential degradation products are separated by ion-pair chromatography using 0.01 M cetyltrimethylammonium bromide as the ion-pairing agent and a polymeric stationary phase. Detection is by fluorescence detection after postcolumn derivatization of the primary amine with ophthalaldehyde and mercaptoethanol (OPA MERC). Optimization of the chromatographic separation and the postcolumn reaction has been carried out, and the method has been applied to the analysis of MK-217 in intravenous solutions and tablet formulations. PMID- 2262532 TI - Variable stringency hybridization of polymerase chain reaction amplified HIV-1 DNA fragments. AB - DNA isolated from the peripheral blood mononuclear cells of HIV-1 seropositive individuals was used for polymerase chain reaction (PCR) amplification of gag and envelope regions. Eight aliquots of the amplified DNA fragments have been subjected to Southern/dot blot analysis, hybridizing with 32P-labelled-BH10 (HIV 1 strain IIIB) at low stringency. After the filters had been autoradiographed, they were cut so that each hybridized band/dot could be subject to variable stringency washing using various ionic concentrations at a fixed temperature. The filter was reconstructed so that the effect of the variable stringency wash might be visualized following a second exposure to Kodak film. The level of activity for each band/dot was measured by counting the 32P or by densitometry analysis of the photographic record. The results allow a plot to be made of the decrease in bound radioactivity against ionic strength. By comparison with a standard curve obtained for HIV-1 strain IIIB amplified fragments subject to similar hybridization and analysis, an estimation of the degree of nucleotide mismatch relative to the BH10 DNA probe can be obtained. The technique provides a rapid means of characterizing PCR amplified fragments. PMID- 2262533 TI - Development and optimization of a hybridization assay for epizootic hemorrhagic disease viruses. AB - Hybridization assays for the double-stranded RNA (dsRNA) orbiviruses causing bluetongue and epizootic hemorrhagic disease are more labor-intensive and less sensitive than enzyme-linked immunosorbent assay (ELISA) and immunoperoxidase assay. Cell-culture EHD virus amplification, rapid extraction, and optimization of RNA blotting conditions were examined to increase sensitivity and decrease labor. Aldehyde RNA denaturations and nylon hybridization membranes resulted in stronger positive hybridization signals. Treatment of infected cells with protease did not increase the yield of viral RNA target. Because RNA extraction is a tedious process, a simple non-phenolic diethyl pyrocarbonate extraction procedure was developed. The sensitivity, versatility, and the reproducibility of hybridization assays are addressed. PMID- 2262534 TI - An immune dot-blot technique for the diagnosis of ocular adenovirus infection. AB - The development of a monoclonal antibody based radio-immune dot-blot technique (IDBT) for the rapid detection of adenovirus is described. 718 conjunctival swabs from patients with acute keratoconjunctivitis were examined by conventional cell culture isolation techniques and IDBT. IDBT identified adenovirus in 64 of 75 culture positive samples and also in a further 34 culture negative samples [Sensitivity (IDBT versus culture) 85.3%; Specificity 92.2%]. IDBT is considered to be a simple, clinically relevant, technique for the rapid identification of adenovirus infection of the eye. PMID- 2262535 TI - Entry and replication of Japanese encephalitis virus in cultured neurogenic cells. AB - The entry mode and growth pattern of Japanese encephalitis (JE) virus in mouse neuroblastoma N18TG2 cells and mouse neuroblastoma x rat glioma NG108-15 hybrid cells were studied by electron microscopy. At two minutes after inoculation, JE virions adsorbed onto and directly penetrated through the plasma membrane of the hybrid cells, whereas virions did not adsorb nor entered the neuroblastoma cells. Correspondingly, the hybrid cells showed assembling progeny JE virions in the cisternae of rough endoplasmic reticulum (RER) 1 day postinoculation (p.i.) although virions were rarely found on the following days during the experiment. On the other hand, progeny virions did not assemble in the RER cisternae of the neuroblastoma cells throughout the experiment. The morphologic observations, therefore, suggest that (a) the hybrid cells express JE-virus receptors which facilitate the viral attachment onto and entry into the cells, while the neuroblastoma cells do not and (b) JE virus replicates very poorly after the entry into the hybrid cells while it does not replicate at all in the neuroblastoma cells. The virus titrations of the media of the neuroblastoma and hybrid cell cultures showed only titers indicative of residual virus of the inoculum that progressively decreased during the experiment. The present results show therefore that of the two neurogenic cell culture lines studied only the hybrid cell line can be used for the study of viral entry and replication, although it is not suited for virus production. Possible reasons for the poor replication of JE virus in the hybrid cells are discussed. PMID- 2262536 TI - Reciprocal interactions between epithelium, mesenchyme, and epidermal growth factor (EGF) in the regulation of mandibular mitotic activity in the embryonic chick. AB - Mandibular epithelia and mesenchyme from chick embryos of Hamburger and Hamilton (H.H.) stage 18-25 were cultured intact, in isolation, or in recombinations in the presence or absence of 5-40 ng/ml epidermal growth factor (EGF). 3H-thymidine labelling demonstrated that mesenchyme influenced epithelial mitotic activity and vice versa. EGF can substitute for the epithelial effect. The stimulation of mesenchymal proliferation by H.H. 18 and 22 epithelia correlated with high levels of epithelial proliferation. Epithelial proliferation was low at H.H. 25 and unaffected by mesenchyme or by EGF. Epithelial stimulation of mesenchymal proliferation began earlier (H.H. 18) than did mesenchymal stimulation of epithelial proliferation (H.H. 22); i.e., within the ages tested, the epithelium initiated these reciprocal mitogenic interactions. That epithelial dependence on mesenchyme coincided with epithelial bone-evoking properties, suggested a) that mesenchyme promotes or maintains epithelial bone-promoting activity and b) that the critical differentiative influence of epithelium on mesenchyme is a mitogenic one. The temporal correlation between a sharp decline in mesenchymal proliferation and termination of the osteogenic epithelial-mesenchymal interaction at H.H. 25 further supports a connection between epithelial maintenance of mesenchymal proliferation and epithelial evocation of osteogenesis. PMID- 2262537 TI - Lack of either chondrocyte hypertrophy or osteogenesis in Meckel's cartilage of the embryonic chick exposed to epithelia and to thyroxine in vitro. AB - Osteogenesis was not initiated when Meckel's cartilages from embryonic chicks of Hamburger and Hamilton (H. H.) stages 38 and 39 were recombined with mandibular epithelia obtained from embryos of H. H. stage 22 (a stage when an epithelial mesenchymal interaction elicits osteogenesis from mandibular mesenchyme) and grafted to the chorioallantoic membranes of host embryos for 7 to 21 days. Failure of osteogenesis was not because the cartilage inhibited or blocked the osteogenesis-initiating capabilities of mandibular epithelium for mandibular epithelia could still elicit osteogenesis when removed from Meckel's cartilages and recombined with mandibular mesenchyme. Chondrocyte hypertrophy is associated with osteogenesis in other cartilages, including Meckel's cartilage from rodent embryos. However, Meckel's cartilages from chick embryos of H. H. stages 34, 38, and 39 failed to hypertrophy when cultured in the presence of 7.5 nM thyroxine (3,3',5-triiodo-L-thyroxine), although H. H. stage 28 tibial chondrocytes cocultured with Meckel's cartilage did hypertrophy. Therefore, avian Meckelian chondrocytes fail to hypertrophy or to produce osteoprogenitor cells in response to stimuli known to evoke these events in other skeletal cells. PMID- 2262538 TI - Genetic study on the mandibular molar size of rats. AB - Tooth size is determined by genetic and environmental factors like other quantitative characters such as body weight and body height. However, the degree of the relative contribution of both factors to the determination of tooth size has not been well clarified. In order to study the genetic and environmental factors affecting tooth size, we carried out a diallel cross mating by the cohabitation of pairs of males and females among 10 strains of rats. The bucco lingual widths of the first, second, and third molars of the right mandible were measured in each offspring of F1 population. The body weight was also measured as a parameter that might indicate systemic growth factor in connection with tooth development. The quantitative genetic analysis was performed based on Wearden's model (Heredity 19:669-680, 1964). As a result, the size of the first and the second molars was more significantly controlled by genetic effect than maternal effect, while maternal effect could not be ignored for the size of the third molar in addition to genetic effect. The genetic effect on body weight became greater with age, while the maternal effect showed its maximum influence upon the body weight around the weaning. It is concluded that the size of the molar teeth beginning to develop in the uterus and to be calcified just after birth was mainly controlled by genetic factor, and that the size of the molar teeth beginning to develop approximately after birth was mainly controlled by maternal effect affecting body weight at the same period. PMID- 2262539 TI - The scientific basis of computed neurophysiologic topography. PMID- 2262540 TI - The development of EEG brain mapping. AB - The field of EEG brain mapping is a collection of many separate techniques for quantified EEG analysis. The most popular technique is the color-coded topographic mapping of frequency content, usually taken in the alert eyes-closed state. This field has developed progressively over 60 years and now is gradually entering use in clinical situations. Accepted clinical uses are still rather limited. A variety of substantial problems exists regarding artifacts, confounding clinical issues, the diversity of available techniques, and statistical interpretation. Clinically, the tests may demonstrate an abnormality but are generally nonspecific regarding the type of responsible pathology. They localize impairment far less well than neuroimaging tests. These digital EEG techniques should not be used separately from the polygraph EEG at this time and should be only used by persons who have sufficient skills, knowledge, and abilities in traditional polygraph EEG interpretation along with additional knowledge and experience in statistical and EEG computer-processing techniques. PMID- 2262541 TI - Visual cues in the interpretation of medical images. AB - The use of the computer in imaging has provided great versatility for the display of medical image information. In order to be useful in a medical sense, the display must be perceptually acceptable to the human observer, who must be able to extract the relevant diagnostic information from the image. Diagnostic information is defined by the imaging task, and the concept of task-dependent image quality is, therefore, very important. Visualization and estimation tasks may require different visual cues for their performance. Visualization tasks require strong boundary cues, whereas intensity estimation tasks require texture cues. Both tasks can be aided by appropriate image displays. Color can be helpful in estimation tasks, and three-dimensional display can aid visualization tasks. No matter what the task or the image, as long as an observer is needed to read out the information, performance is the final arbiter of the goodness of the image. PMID- 2262542 TI - Visual information processing of computed topographic electrical activity brain maps. AB - Effective display of computer-generated biomedical images draws on computer graphics and image processing, display technology and human factors, visual psychophysics and perception, cognitive psychology, and the new field of scientific data visualization. In converting from raw, acquired data to a visual display, developers need to know the limitations of the data and of the display technology. To obtain reliable inferences about the clinical or physiological state of the patient requires that the computer display be matched to the visual information-processing competence and limitations of human observers. The issues that should be considered by both developers and users of computer-based display technologies to enhance clinical performance in observation and diagnosis are surveyed with reference to electrical activity brain maps. PMID- 2262543 TI - Precautions in topographic mapping and in evoked potential map reading. AB - First, we consider the main points that must be addressed when constructing topographic maps: types of projection, methods of interpolation, number and locations of recording electrodes, and color scales. Data integrity and precautions in map interpretation are then examined for the case of evoked potential data. PMID- 2262544 TI - Adequacy of the International 10-20 electrode system for computed neurophysiologic topography. AB - The adequacy of the International 10-20 System is reviewed in light of demands imposed on the accuracy of lead placement by improvements in spatiotemporal brain electrical activity mapping technology. Computed tomography (CT) and magnetic resonance imaging (MRI) studies reveal that the most frequent sources of inaccuracy of electrode locations are difficulties in defining the inion, variance in the anatomy of the occipital bone, inconspicuous sagittal deformities, variance of sulcal pattern, and brain width asymmetries. Owing to these factors, electrodes placed bilaterally and equidistant from the nasion inion line may not be homotopically located. Therefore, the authors suggest that practitioners who employ the 10-20 System in order to gain precise and more individualized laterality information do so with extreme caution until the range of placement and interpretative errors is more precisely determined using CT/MRI assisted EEG. PMID- 2262545 TI - Statistical aspects of neurophysiologic topography. AB - The multitude of electrodes and the large number of EEG variables used in neurophysiologic topography call for new inferential statistical concepts in the analysis of data from corresponding studies. These concepts must take into consideration that significance levels and confidence coefficients lose their numerical meaning in situations with many significance tests and/or interval estimates performed on the data from one sample of subjects or patients. The application of one of these concepts. Descriptive Data Analysis (DDA), is discussed, using the data from a real EEG mapping example. Also, the use of DDA is proposed for the judgement of normality of EEG maps. PMID- 2262546 TI - A critical review of clinical applications of topographic mapping of brain potentials. AB - A brief review of several aspects of topographic mapping of brain potentials is presented. Some general factors of importance for the construction of brain maps are considered, namely, how to sample in space and how to deal with the influence of the reference electrode. The issue of what is a representative map is examined for the cases of both steady and dynamic states. Special attention is paid to the methodology of assessing whether a brain map may be considered "normal" or "abnormal" on the basis of multivariate statistical considerations. Besides being used to visualize statistical comparisons between sets of EEG data, brain maps may be used as a first step for a model-based analysis in order to estimate the localization of equivalent dipolar sources of the electrical activity within the brain. The question of whether brain maps may yield added value to multivariate quantitative EEG analysis is examined for the following clinical cases: (1) developmental disorders; (2) space-occupying lesions; (3) epilepsy; (4) cerebrovascular diseases; (5) dementia; and (6) psychiatric diseases. It is concluded that brain mapping may be valuable as a comprehensive and attractive form of data reduction to represent a complex set of multichannel (optimally at least 64) EEG signals, but only if the user is well aware of the pitfalls involved. Brain mapping might supplement quantitative topographic analysis if it can be used as the basis for solving the inverse problem in EEG. More extensive and well-controlled studies are necessary in order to establish the clinical value of complementing a routine EEG examination with brain mapping. PMID- 2262547 TI - An anatomical study on the distribution of the temporal branch of the facial nerve. AB - In an attempt to define the distribution of the temporal branch of the facial nerve, 30 facial halves of 15 Japanese cadavers were dissected. The tissue plane in which the temporal branch ran was investigated and the relationship between this nerve and the surrounding tissues observed. To quantify the distribution, the distance from the bony lateral canthus (LC) to the points where the temporal branches crossed two standard lines, (L1 and L2) were measured. These latter were determined according to the skeletal landmarks. The temporal branch consistently lay along the undersurface of the temporoparietal fascia. But its depth below the skin was not constant because the amount of overlying adipose tissue varied and it was localized within a limited area. The temporal branch generally branched into 3 or 4 rami and its trajectory was either straight or curved, depending on the relationship between the middle and the posterior ramus. The distances from LC to each point were relatively constant and there was no difference between the right and the left side. It is important for surgeons to know the quantified course of the temporal branches based on the skeletal landmarks. As a consequence of the quantification, it was possible to establish new guidelines for protection of the entire temporal branch from surgical injury. PMID- 2262548 TI - The case for postoperative orthodontics in orthognathic surgery. AB - In patients with orthognathic problems, in whom a combination of surgery and orthodontics is required, it seems to us better to defer orthodontic treatment until after surgery has been completed and a possible relapse tendency has petered out. This conclusion is reached on the basis of arch instability and the incidence of root resorption as reported in the orthodontic literature. The soundness of "permanent retention" after orthodontic therapy is questioned. The author's concepts are illustrated with a few case reports. PMID- 2262549 TI - Intermaxillary fixation of mandibular fractures with the bracket-bar. AB - An alternative method for intermaxillary fixation of mandibular fractures using a bracket-bar bonded to the teeth is described. The technique is easy to use, improves gingival health, reduces anaesthesia time and reduces the risk of transmitting blood-borne diseases to the surgeon through perforating injuries from wires. PMID- 2262550 TI - Congenital prearticular temporo-mandibular ankylosis in two siblings. AB - A report of congenital ankylosis of the temporo-mandibular joint has only very rarely been published. The existence of this entity has been met with great scepticism and therefore believed to be due to perinatal trauma and subsequent development of the ankylosis. However, publications are now available of observations at birth after an uneventful pregnancy and spontaneous delivery. Our cases are the first publication of congenital TMJ ankylosis in two siblings, although there are hints in the histories in two other papers that a sibling may have suffered from the same condition. We discuss the hypothesis that the potential to ankylose in the temporomandibular area is a congenital disorder as in our cases, and that even later in life trauma or infection are only supervening initiating factors. PMID- 2262551 TI - Severe lower lip disfigurement resulting from war injuries. Management by local tissue traction. AB - A new technique is presented for severe lower lip disfigurement resulting from war injury. The procedure consists of a Kirschner wire used as the means of traction on the remaining soft tissue of the lower lip, using the upper teeth or pyriform aperture bone as remote fixed points for tissue traction. The technique which is simple, short, and effective provides an acceptable appearance, texture, and skin sensation. It proved to have several advantages over other more commonly employed methods. PMID- 2262552 TI - Reconstruction of gunshot wounds of the mandible. 128 cases treated by autogenous iliac crest bone grafts. AB - 128 cases of mandibular reconstruction for defects due to gunshot injuries were treated by various types of autogenous iliac crest bone grafts during a period of 4 years and six months. The survival rate of these grafts was 98.43 per cent. PMID- 2262553 TI - The alterations in sensitivity of the infraorbital nerve following fractures of the zygomaticomaxillary complex. AB - 52 patients with fractures of the zygomaticomaxillary complex associated with hypoaesthesia of the infraorbital nerve were evaluated as to the degree of residual impairment in sensitivity. Those with minor displacements or no displacements at all showed complete recovery. Early treatment was associated with better results, while no correlation was found between the degree of anatomical reduction and the improvement in nerve sensitivity. The results appeared to be better when the lateral orbital approach was part of the treatment. PMID- 2262554 TI - Optic nerve blindness following a malar fracture. AB - Optic nerve blindness following a malar fracture is an uncommon and usually permanent complication. When the loss of vision is immediate and total, the prognosis is poor. The case of a patient who suffered immediate and complete loss of vision after a malar fracture is presented. Computed tomography revealed compression of the optic nerve by bony fragments. No improvement was observed after megadose steroids and surgical treatment. The incidence, pathogenesis, diagnostic approach and therapeutic possibilities are discussed and the importance of establishing precisely the moment of the loss of vision is stressed. PMID- 2262555 TI - Basaloid-squamous carcinoma of larynx metastatic to the skin of the nasal tip. AB - Basaloid-squamous carcinoma is a rare, highly malignant epithelial tumour with problematic histological characteristics and a poor prognosis. This unusual tumour has been described in the tongue, hypopharynx, and larynx. A unique case of basaloid-squamous carcinoma of the larynx metastatic to the skin of the nasal tip is presented. The literature regarding the histopathological and clinical aspects of basaloid-squamous carcinoma is reviewed. PMID- 2262556 TI - Pathology across Europe 4: Chemical pathology. PMID- 2262557 TI - Current concerns in haematology. 2: Classification of acute leukaemia. PMID- 2262558 TI - Use of cytoplasmic 5'nucleotidase for differentiating malignant from benign monoclonal gammopathies. AB - Bone marrow smears from 15 patients with multiple myeloma, 15 patients with monoclonal gammopathy of undetermined significance (MGUS), and 15 control subjects were examined for the presence of cytoplasmic 5'nucleotidase (c5NT) in plasma cells. Plasma cell positivity for c5NT (mean and 95% confidence interval) in patients with multiple myeloma numbered 46.4% (38.0-54.8%), in those with MGUS it was 15.3% (11.1-19.6%), and in control subjects it was 1.2% (0.3-2.1%). These findings indicate that c5NT can be used to differentiate benign from malignant monoclonal gammopathies. PMID- 2262559 TI - Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa. AB - Specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor (PSTI). In normal colonic mucosa PSTI was found in the goblet cells in the basal parts of the crypts. In adenomas of tubular, villous, and tubulo-villous types PSTI was also found in the upper parts of the polyps, usually occurring in the regeneration zone. There was a more intense staining reaction in polyps with increased atypia. Carcinomas of different types and of various grades of differentiation and of in situ type did not contain PSTI. These findings indicate that PSTI could be a marker for adenomatous rather than carcinomatous epithelium in the colon. Furthermore, the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition. PMID- 2262560 TI - Spherical connective tissue inclusions in epithelial hyperplasia of the breast ("collagenous spherulosis"). AB - Partial myoepithelial differentiation is common in simple epithelial hyperplasia (epitheliosis) of the breast but functional myoepithelial differentiation with basement membrane production is exceedingly rare. A peculiar change of hyaline globules within benign epithelial hyperplasia has been recognised before as "collagenous spherulosis" and type IV collagen has been shown by immunohistochemistry. Another seven cases are described which show the presence of laminin and collagens IV and III within the proliferation. Electron microscopy examination of two cases using material retrieved from the wax block showed varying degrees of myoepithelial differentiation of the cells immediately surrounding the spherules and basal lamina material, including mature collagen fibrils in one case. The degree of myoepithelial differentiation of the cells surrounding the spherules seemed to correlate with the differing types and amounts of extracellular matrix in the spherule. Histopathologists should be aware of this rare change as it may be misinterpreted as in situ carcinoma. PMID- 2262561 TI - Measurement techniques for melanoma: a statistical comparison. AB - Inter- and intra-observer variation in measuring the depth of invasion of malignant melanomas was assessed using three different techniques: eye-piece graticule, stage Vernier, and projection image analysis. Significant variation was found for all methods but was least pronounced with the stage Vernier. It is recommended that this should be the preferred technique for routine use. PMID- 2262563 TI - Serum alanine transaminase (ALT) reference ranges estimated from blood donors. AB - It has been suggested that an increase in serum alanine transaminase (ALT) activity in blood donors may identify infection with non-A, non-B hepatitis. To facilitate identification of such donors, the reference range for ALT was measured on a Technicon SMAC 1 Analyser, using serum from 364 blood donors and 567 plasmapheresis donors. The distribution of ALT activities displayed a positive skewness, and so both logarithmic transformation and subsequent calculation of mean and standard deviation as well as non-parametric analysis were used to obtain best estimates of reference ranges for men and women, 5-65 IU/1 and 5-35 IU/1, respectively. ALT activities were found to be higher in plasmapheresis donors than in normal blood donors of both sexes, and it is postulated that this difference may be related to the increased frequency of donation in the former group. PMID- 2262562 TI - New technique for analysing conjugated bile acids in gastric juice. AB - A new technique of high performance liquid chromatography (HPLC) was developed for the analysis of conjugated bile acids in gastric juice. The assay is rapid, sensitive, and highly specific for bile acid conjugates over the range 30-10,000 mumol/l and is not affected by the presence of food. Ten patients with a variety of common upper gastrointestinal disorders underwent continuous gastric aspiration for 16 hours, including a fasting, post-prandial, and nocturnal period, and aliquots of aspirates were analysed every two hours by the HPLC technique for the six most prevalent bile acid conjugates present in human hepatic bile. Intragastric bile acid concentrations were lowest in the post prandial period and highest in the early hours of the morning. Conjugated bile acid proportions, or profiles, varied considerably from patient to patient, but tended to remain uniform over time in individual patients. It is concluded that HPLC is superior to enzymatic techniques for the analysis of conjugated bile acids in the upper gastrointestinal tract. PMID- 2262564 TI - Evaluation of a prototype for a reference platelet counter. AB - A semiautomated single channel aperture-impedance particle counter was developed as a prototype for a reference platelet count for assigning values to reference preparations used in automated blood cell counts. The instrument is equipped with sheath flow and an aperture orifice of 50 microns in diameter and 60 microns in length to eliminate non-axial flow and minimise coincidence errors. Use of fixed volume and red blood cell:platelet ratios obviate dilution errors. The counter was assessed in accordance with the International Committee for Standardization in Haematology protocol for evaluation of automated blood cell counters. The counter provided a high level of linearity and precision, accurate coincidence correction, controlled volume, stability and negligible carryover. PMID- 2262565 TI - Erythroid colony growth from peripheral blood and bone marrow in polycythaemia. AB - Erythroid colony growth in the presence and absence of erythropoietin was compared in 23 patients with primary proliferative polycythaemia (PPP), nine with idiopathic erythrocytosis, 10 with secondary polycythaemia, 15 with pseudopolycythaemia and in 76 normal subjects. Erythroid colonies growing without erythropoietin stimulation (endogenous erythroid colonies) from peripheral blood (BFU-E) were found in 20 of 22 patients with PPP and in two of seven with idiopathic erythrocytosis. None was found in secondary polycythaemia, pseudopolycythaemia, or in normal subjects. Small numbers of endogenous colony forming units-erythroid (CFU-E) (though not BFU-E) were cultured from the bone marrow of three of 24 normal subjects, suggesting that peripheral blood cultures provide a more specific indicator of clonal erythropoiesis. Peripheral blood endogenous erythroid colony growth is an effective and convenient means of distinguishing patients with clonal erythrocytosis and may be of particular value when iron deficiency obscures the diagnosis of PPP on conventional criteria. PMID- 2262566 TI - Bone marrow stromal cell changes in haematological malignancies. AB - Stromal cell numbers from subjects with no haematological disease and those with acute myeloid leukaemia (AML), chronic granulocytic leukaemia (CGL), acute lymphatic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) were compared to determine their role in malignancy. Frozen sections of trephine biopsy specimens from iliac crests were stained for endogenous alkaline phosphatase activity, endogenous acid phosphatase activity, and, using immunocytochemical methods, for endothelial cells (anti-factor-VIII related antigen) and macrophages and related cells (EBM/11). In granulocytic malignancies, whether acute or chronic, alkaline phosphatase positive reticulum cells (AL-RC) and vascular endothelial cells were generally increased. In lymphoid malignancies, the numbers of AL-RC were generally reduced. Numbers of vascular endothelial cells seemed to be normal in ALL but reduced in foci of NHL. Macrophages are numerous in normal marrow, and their numbers seemed to be normal in granulocytic lesions but were more variable and sometimes reduced in ALL and NHL. Lymphoid malignancies, therefore, have a destructive effect on some stromal elements; granulocytic malignancies are associated with normal or increased numbers of stromal cells. A possible consequence of depleted stromal cells might be slower reconstitution of normal haemopoiesis after treatment. The large numbers in granulocytic malignancies raises the possibility of synergistic stimulation between stromal and neoplastic cells. PMID- 2262567 TI - Comparison of three-compartment Petri dishes and individual plates for routine culture of vaginal swabs. AB - Recovery of aerobes and facultative anaerobes from 200 consecutive randomly selected high vaginal swabs was evaluated using three-compartment Petri dishes containing Sabouraud, dextrose agar, GC selective agar, and chocolate agar. The method was compared with the traditional method using individual Petri dishes. The two methods produced comparable results both in terms and quantities of organisms recovered from the specimens. As three-compartment Petri dishes use less agar, save time in culturing specimens, yet still maintain the same standard of culture, they provide a more economical alternative to the traditional method for routine culture of vaginal swabs. PMID- 2262568 TI - Non-specific reactions in enzyme linked immunosorbent assays for serum antibody to entamoeba histolytica and Giardia lamblia in non-endemic areas. AB - Serum samples from 20 Indian children with diarrhoea were compared with those from 20 children resident in the United Kingdom who had been diagnosed as having ulcerative colitis, or Crohn's disease, or indeterminate colitis using enzyme linked immunosorbent assays specific for Entamoeba histolytica and Giardia lamblia. More than 50% of the United Kingdom patients had high IgG responses in ELISAs for E histolytica and G lamblia. A confirmatory ELISA showed that the British sera reacted specifically to bovine serum proteins rather than to protozoal antigens. Prior incubation of sera with 5% bovine serum prohibited this reaction. Bovine serum is an integral part of the crude soluble antigen used in most ELISAs for E histolytica and G lamblia and needs to be replaced with purified antigen preparations. The British sera also reacted to other commonly used blocking agents such as bovine serum albumin, casein, and normal sheep serum. These reactions were attributed to uptake of dietary antigens or an enhanced immunological response to these antigens in patients with inflammatory bowel disease. PMID- 2262569 TI - Antibody coated bacteria in urine of patients with recent spinal injury. AB - Twenty patients with an acute spinal injury were prospectively studied to assess the clinical importance of antibody coated bacteria (ACB) in the urine and the association among the different bacterial species with a positive antibody coated bacteria test. Clinical urinary tract infection was associated with a positive ACB test on 45% of occasions. Three hundred and ninety nine urine samples containing 541 bacterial isolates were assessed for the presence of ACB; 13% were found to be positive and 87% negative for ACB; 67% of urines contained a single bacterial isolate. Pseudomonas aeruginosa was most commonly associated with clinical urinary tract infection, found in 25% of episodes, followed by Proteus mirabilis (17.5%), Klebsiella sp (12.5%), and Proteus morganii (10%). Providencia stuartii, however, was most commonly associated with a positive ACB test (found in 17%). Other bacteria associated with a positive ACB test included Klebsiella sp (14%), Acinetobacter sp (12.5%), Pseudomonas aeruginosa (12%), Citrobacter sp (11.5%). A positive ACB test is not to be expected from a patient with spinal injury who has a catheter in place, and the test may provide a useful guide to identify those patients with an invasive infection. It is doubtful that a decision to treat or not treat bacteriuria could rest on the identification of the bacterial species alone. PMID- 2262570 TI - Lectin typing of Campylobacter isolates. AB - Isolates of Campylobacter jejuni, C coli, C fetus and C laridis were tested for agglutination reactions with a panel of five lectins: Arachis hypogaea, Bauhinia purpurea, Solanum tuberosum, Triticum vulgaris and Wisteria floribunda. Twenty three patterns of agglutination (lectin types) were recorded among 376 isolates. Patterns were consistent and reproducible. Only 4.5% of isolates were untypable because of autoagglutination. Some lectin types were found exclusively or predominantly in a species, but others were shared between species. Forty two per cent of C jejuni and 35% of C coli isolates belonged to lectin type 4. There was no apparent correlation between lectin type and serotype; different lectin types were found among strains of single Penner and Lior serotypes. Lectin typing is a simple and economical procedure suitable for use in non-specialist laboratories, either as an adjunct to serogrouping or, after further development, as a sole typing scheme. PMID- 2262571 TI - Campylobacter-like organisms in heterotopic gastric mucosa of the upper oesophagus. PMID- 2262572 TI - Thrombotic thrombocytopenic purpura (TTP) complicating leptospirosis: a previously undescribed association. PMID- 2262573 TI - Implications of delay in culturing for Campylobacter. PMID- 2262574 TI - Flow cytometric DNA in ectopic pregnancy. PMID- 2262575 TI - Monocyte esterase deficiency: familial or environmental? PMID- 2262576 TI - AgNORs and follicular lymphomas. PMID- 2262577 TI - Consequences of the provision of laboratory services of the National Health Service by commercial firms. PMID- 2262578 TI - Examination of faeces for bacterial pathogens. PMID- 2262579 TI - The role of histopathology in the diagnosis and prognosis of periodontal diseases. AB - The histological evaluation of surgical biopsies from affected tissues is a standard way of assessing pathological change and determining treatment in many diseases. In most forms of periodontal disease, however, this approach finds limited application. Here, we review what uses the histopathological approach has in the study and evaluation of the periodontal diseases. Current understanding of the changes in epithelial anatomy during pocket formation, the cellular composition and dynamics of the inflammatory infiltrate and the mechanisms of bone resorption and repair are reviewed from the perspective of the information available from microscopical investigation, including the uses and potential application of modern immunocytochemical methods to these questions. The usefulness of histological study of biopsy material is reassessed in the light of advances made in immunohistochemical techniques and their application to gingival inflammatory infiltrates and epithelia. Such techniques offer immediately valuable research opportunities with potential for diagnostic applications, noteably the recognition of phases of destructive activity and their differentiation from periods of effective host defence. PMID- 2262580 TI - Changes in subgingival microbiota during puberty. A 4-year longitudinal study. AB - It was the purpose of the present investigation to monitor the composition of the subgingival microbiota at selected sites in individuals passing through puberty and to correlate observed changes with the development of pubertal maturation. Between the ages of 11 and 14 years, pubertal and skeletal maturation was monitored annually in 22 boys and 20 girls. During this time, subgingival microbial samples were taken every 4th to 5th month (10 times in 4 years) mesially of the upper first molars. High values in total bacterial counts were reached after the onset of puberty, followed by a decrease towards the end of the observation period. The frequency of detection of Actinomyces odontolyticus and of Capnocytophaga sp. increased with time. The frequencies of other selected species, specifically of black pigmenting Bacteriodes sp. were not found to increase when tested by linear and quadratic models of time trend. However, a statistically significant rise in the frequency of detecting B. intermedius and B. melaninogenicus was noted in the initial pubertal phase identified by the onset of testicular growth in boys (p = 0.05). A significant relationship also existed between testes growth and increase of A. odontolyticus (p less than 0.01). In girls, a similar increase was obtained for A. odontolyticus when studied in relation to the Tanner scores for breast development (p less than 0.01). The changes observed in the subgingival microbiota during puberty may be related to the development of gingivitis, which was demonstrated by a higher tendency for gingival bleeding during the course of the pubertal maturation process. PMID- 2262581 TI - The effect of triclosan, stannous fluoride and chlorhexidine products on: (I) Plaque regrowth over a 4-day period. AB - A number of substances have been incorporated into toothpastes or gels to inhibit plaque regrowth. The aim of this study was to evaluate triclosan and stannous fluoride products for plaque inhibitory properties by comparison with a chlorhexidine or saline rinse and a control product which was a conventional commercially available toothpaste. In a blind 8 cell cross-over study, 15 volunteers rinsed 2 x a day for 4 days with slurries of the products or the saline and chlorhexidine solutions. No other form of oral hygiene was performed and plaque regrowth from a zero baseline was recorded by plaque score and plaque area. Plaque regrowth was significantly less with the chlorhexidine rinse and significantly greater with the saline rinse compared to the toothpaste and gel products. No significant differences were found between the test and control products. The results again demonstrate that commercially available toothpastes have plaque inhibitory effects which so far appear difficult to improve upon by the addition of specific ingredients, in this case stannous fluoride or triclosan. Commercially available products of known activity would appear useful benchmarks for comparison of experimental formulations. PMID- 2262582 TI - The effect of triclosan, stannous fluoride and chlorhexidine products on: (II) Salivary bacterial counts. AB - A previous study demonstrated that triclosan and stannous fluoride containing oral hygiene products reduced plaque regrowth compared to saline but were not more effective than a conventional commercial fluoride/anionic detergent toothpaste. To further understand these results, this study measured the persistance of antimicrobial activity of the same products by recording the duration of salivary bacterial count reductions following a single exposure to each product. Comparison was also made with a chlorhexidine rinse as the positive control. From a panel of 16 volunteers, in an 8-cell randomised cross-over designed study, salivary bacterial counts were recorded at baseline and to 420 min. All test and control products were significantly more effective than saline and significantly less effective than chlorhexidine at suppressing bacterial counts. Unlike chlorhexidine, evidence of bacterial recovery was apparent after the 30-min sampling time. There were essentially no significant differences between the test and control products, although the stannous fluoride toothpaste performed marginally better than other products. The findings are consistent with the plaque regrowth results previously obtained and again demonstrate to date that it is difficult to surpass the antimicrobial and plaque inhibitory properties of conventional commercially available toothpastes by the addition of antimicrobial agents such as triclosan and metal salts. PMID- 2262583 TI - 5-year results of a longitudinal study of early periodontitis in 14- to 19-year old adolescents. AB - This 5-year longitudinal study monitored 167 subjects at ages 14.3, 16.0 and 19.6 years. The aims were (1) to determine loss of attachment greater than or equal to 1 mm in the study group over the 5-year period; (2) to relate baseline levels of oral deposits and gingivitis to the 5-year increment of loss of attachment; (3) to determine whether subjects who had developed loss of attachment greater than or equal to 1 mm by age 16 years were more susceptible to further development of loss of attachment; (4) to evaluate loss of attachment indices. Loss of attachment, plaque, subgingival calculus, gingival bleeding and gingival colour change were measured. At baseline, 3% of subjects had loss of attachment greater than or equal to 1 mm and less than 1% of sites were involved. By age 19 years, 77% had loss of attachment greater than or equal to 1 mm, and 31% of sites were affected. There was a significant correlation between the presence of subgingival calculus at baseline and the 5-year increment of loss of attachment (Pearson's r = 0.26 p less than 0.001). Subjects who had developed loss of attachment by age 16 years still had significantly more sites affected at the more severe 2 mm level 3 years later than their peers (p less than 0.05). The results suggest that a flexible approach is needed in selecting indices of loss of attachment for epidemiological investigations. PMID- 2262584 TI - Cementum thickness and mesial drift. AB - Cementum thickness increases uniformly with age, and questionably from functional stimulation due to tensional forces. Mesial drift of teeth results in tensional forces on distal root surfaces. This study evaluated whether there was any discernible effect on cementum thickness related to mesial drift in humans. The material consisted of maxillary and mandibular bicuspids and molars with their surrounding periodontia from 5 humans (mean age at death, 48.6 years). The teeth and tissues had been sectioned histologically in a mesio-distal plane, and the analysis for each tooth was done using 3 step-serial sections from the mid buccolingual region. On the mesial and distal surface of each tooth, cementum thickness was measured in microns at 3 defined locations at a level representing the mid-point of root length for bicuspids and molars. Means from the measurements on mesial and distal surfaces were compared using descriptive and and inferential statistical methods. For each individual tooth analyzed, the cementum was thicker on the distal surface (range greater, 32-107%; mean, 69%). The statistical comparisons showed that cementum thickness on the distal surface was significantly greater for bicuspids (mesial, 135 microns: distal, 216 microns), molars (mesial, 154 microns: distal, 284 microns), and all teeth combined (mesial, 154 microns: distal, 284 microns). The magnitude of this difference became greater with increasing age. It was concluded that cementum thickness was markedly greater on the distal surfaces of teeth from adult humans, and that this may be due to functional stimulation from mesial drift over time. PMID- 2262585 TI - Absence of bleeding on probing. An indicator of periodontal stability. AB - Following active periodontal therapy, 41 patients were incorporated in a maintenance program for 2 1/2 years with recall intervals varying between 2-6 months. At the beginning of each maintenance visit, the periodontal tissues were evaluated using "bleeding on probing" (BOP). Reinstrumentation was only performed at sites which bled on probing. However, supragingival plaque and calculus was always removed. Pocket probing depths and probing attachment levels were recorded after active treatment and at the conclusion of the study. Progression of periodontal disease was defined by an observed loss of probing attachment of greater than or equal to 2 mm. The reliability of the BOP test as a predictor was evaluated by calculating sensitivity, specificity, accuracy, and positive and negative predictive values. While only a 29% sensitivity was calculated for frequent bleeding, the specificity was 88%. The fact that the positive predictive value for disease progression was only 6% and the negative predictive value was 98% renders continuous absence of BOP a reliable predictor for the maintenance of periodontal health. PMID- 2262586 TI - Efficiency of split-mouth designs. AB - The purpose of this paper is (1) to investigate the similarity of the amount, distribution, and severity of periodontal disease of the within-patient experimental units, (2) to estimate the relative efficiencies of split-mouth designs when compared to whole-mouth designs, and (3) to discuss how stratification on initial pocket depth can result in large differences in the power of the test-statistics in the different disease categories. Periodontal disease characteristics are not always homogeneously distributed over the within patient experimental units and this heterogeneity can reduce the efficiency of split-mouth designs. In particular, if analyses are stratified on initial pocket depth, sites with an initial probing depth deeper than 6 mm may be small in number and asymmetrically distributed when compared to sites with an initial probing depth less than 6 mm. This may result in large differences of the power of the test statistics among the different disease categories and should lead to a careful interpretation of the statistical significance tests. When disease characteristics are symmetrically distributed over the within-patient experimental units and a sufficient number of sites is present per experimental unit, the split-mouth design can provide moderate to large gains in relative efficiency. In the absence of a symmetric disease distribution, whole-mouth clinical trials may be preferable. PMID- 2262587 TI - Optimal dosage of chlorhexidine acetate in chewing gum. AB - In a previous study, 800 mg pieces of sorbitol-flavored gum, each piece containing 5 mg chlorhexidine (CHX) acetate, when chewed 2 at the time 5 x daily, were found to have an excellent plaque growth inhibiting effect. The aim of Trial 1 of the present study was to assess whether chewing only 2 x daily, 2 pieces of the same concentration CHX gum for about 10 min would be as effective. 6 dental students participated in the 3 x randomly crossed over double-blind clinical trial. During the 5-day chewing periods, no other oral hygiene measures were allowed. The Hibitane Dental (HD) rinse was used as a positive and the gum base containing neither CHX nor the sweetening agent as a negative control. At the end of each test period, recordings were made for the plaque index (PII), the plaque wet weight (PWW) and the relative area of plaque covered tooth surface (plaque area %). Chewing of CHX gum twice daily inhibited plaque growth as effectively as the HD rinse. The aim of Trial 2 was to assess the antiplaque effect of lower concentration CHX gums with, hopefully, a less unpleasant taste. For this trial, 8 dental students were recruited to chew 2 x daily during 6-day periods two 800 mg pieces of sorbitol-flavored gum, each piece now containing either 5 mg, 4 mg or 3 mg CHX acetate. The effect of these dosages did not differ from the effect of the HD rinse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262588 TI - Sulfadiazines reduce gingivitis and plaque formation in beagle dogs. AB - The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on reducing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. 12 beagle dogs were scaled, root planed and pumiced to bring them to a similar level of gingival health, prior to placing them on a diet of Purina Dog Chow softened with canned gravy and molasses to promote the build-up of plaque and the initiation of gingivitis. At the end of 8 weeks, the dogs were determined to have substantial bacterial plaque accumulation and apparent gingivitis. Thereafter, 4 dogs were treated 2 x daily with topical applications of 3% zinc sulfadiazine; 4 dogs were treated with 2% silver sulfadiazine while 4 dogs were treated with placebo gel serving as control over a 14-week treatment period. By week 2, the zinc and silver sulfadiazine dogs showed a significant decrease in gingival index which was maintained throughout the study. Additionally, by week 2, the % of sites with bleeding was also seen to decrease significantly in the experimental groups. The plaque index remained consistent in all 3 groups until week 6 when the 2 experimental groups indicated significant decrease in plaque accumulation as compared to controls. Probing depths were also seen to decrease significantly in the experimental groups after 10 weeks of therapy. The mean stain index was similar in all 3 groups of dogs throughout the study. Data indicate that both zinc and silver sulfadiazine inhibit plaque formation and reduce existing gingivitis in beagle dogs. PMID- 2262589 TI - Cytoarchitecture of the human dorsal raphe nucleus. AB - Serial 50 microns Nissl-stained sections through the midbrain and pontine central gray of four adult humans (mean age 56 years, mean postmortem delay 3 hours) were analysed and the subnuclei of the dorsal raphe nucleus (DR) delineated on the basis of neuronal morphology and density. Five subnuclei were apparent: the interfascicular, ventral, ventrolateral, dorsal, and caudal. The area of each subnucleus was measured in sections selected at regular intervals throughout the length of the DR. The number of neurons was counted and their density within each subnucleus calculated. The dorsal subnucleus was the largest and contained the majority of neurons but had the lowest neuronal density. The ventrolateral subnucleus had the highest density of neurons. A total of 235,000 +/- 15,000 neurons (average of 1,200 +/- 200 neurons per section) were found within a volume of 71.3 +/- 4.5 mm3 of DR with a mean neuronal density of 3,300 +/- 200 neurons/mm3. Morphometric and morphological analysis of DR neurons revealed four distinct neuron types: round, ovoid, fusiform, and triangular. These types of neurons characterized particular subnuclei. The location and boundaries of the subnuclei of the human dorsal raphe are presented in the form of an atlas. The subdivisions described are similar to that described in other mammals. On the basis of this information the location of particular projection neurons within the human dorsal raphe can be predicted and the effects of disease on this nucleus may be forecast. PMID- 2262590 TI - Variability of light-evoked response pattern and morphological characterization of amacrine cells in goldfish retina. AB - Amacrine cells of the goldfish retina were characterized electrophysiologically and subsequently labelled by intracellular injection of horseradish peroxidase. An attempt was made to broaden the electrophysiological classification of the cells. Light-evoked sustained amacrine cell responses were divided into two subtypes depending on colour opponency. Colour-coded responses (red/depolarizing and green/hyperpolarizing) were found to arise in amacrine cells possessing highly polarized dendritic fields; the dendrites were monostratified in the proximal half (sublamina b) of the inner plexiform layer. Non-colour-opponent sustained responses also arose in monostratified units, but the level of dendritic ramification was in sublamina a or b (hyperpolarizing or depolarizing units, respectively). Transient (ON-OFF) responses were associated mainly with bi or multi-stratified or diffuse amacrine cells. Some variability was observed in the sizes of the dendritic fields in different sublaminae. There was a tendency for units with brisk components of responses to be narrowly stratified in the inner plexiform layer. Some units possessed "distant" dendrites. Several aspects of structure-function correlation in amacrine cells are discussed. PMID- 2262591 TI - Structure of the olfactory bulb of the hedgehog (Erinaceus europaeus): a Golgi study of the intrinsic organization of the superficial layers. AB - The intrinsic organization of the mitral cell, external plexiform, and glomerular layers of the main olfactory bulb of the insectivore hedgehog were studied with the Golgi method. This study completes our previous description of the cell types in the granule cell layer in the same subject (Lopez-Mascaraque et al., J. Comp. Neurol. 253:135-152, '86). In the present contribution the morphology of mitral, internal, and middle tufted cells is described with particular interest in the formation and arrangement of glomerular tufts by the primary dendrites, and the disposition of the secondary dendrites. Three types of intrinsic cells were found in the external plexiform layer: Van Gehuchten cells, satellite cells, and horizontal cells. All these cells display unusual patterns of branching processes that were difficult to classify as dendritic or axonal. The close relationship between some processes of the satellite cells with the mitral or tufted cell dendrites is noted, suggesting that these cells may be inhibitory in nature. The external tufted cells are described, and several aspects pertaining to their morphology were considered in order to distinguish them from periglomerular cells and from the remaining tufted cells. External tufted and periglomerular cells appear to be intrinsic neurons, having axons distributed in the periglomerular region, most probably devoted to relating different olfactory glomeruli. The arrangement of glomeruli in the glomerular layer and distinctive characteristics with respect to other mammals were considered from a comparative point of view. PMID- 2262593 TI - The anterior ectosylvian sulcal auditory field in the cat: I. An electrophysiological study of its relationship to surrounding auditory cortical fields. AB - The extent of a region containing acoustically responsive neurons within the anterior ectosylvian sulcus and its relationship to surrounding gyral auditory cortical fields was examined in chloralose-anaesthetized cats. Multiple microelectrode penetrations were made orthogonal to the middle and anterior ectosylvian gyral surfaces, and longer penetrations were made into the dorsal and ventral banks and fundus of the anterior ectosylvian sulcus. The quantitative and qualitative auditory response characteristics of neurons and neuron clusters in the sulcal banks and surrounding regions were mapped in detail, and the degree of overlap of auditory and visual neurons within the sulcus was determined by routinely testing for responsiveness to a gross light flash. The detailed results from three animals and a summary of all penetrations into the sulcus are presented. The anterior ectosylvian sulcal field (Field AES) lay deep within the banks and fundus of the posterior three quarters of the sulcus. A combination of changes in the auditory response characteristics of neurons (i.e., in optimal stimulus, latency, and frequency tuning), and the presence of visually responsive cells, distinguished this field from surrounding fields. The distinction between the anterior ectosylvian field and extensions of the nearby tonotopic fields (i.e., primary and anterior auditory fields) into the dorsal and ventral banks of the dorsoposterior sector of the sulcus was readily made on the basis of these characteristics. The distinction between the anterior ectosylvian field and extensions of the second auditory field into the ventral bank of the middle sector of the sulcus was more difficult and there were differences between animals in the transition between these fields. Anterior ectosylvian sulcal field responses did not extend into the dorsal bank in anterior parts of the sulcus but were restricted to fundal regions, an observation consistent with the presence of the fourth somatosensory field in the dorsal bank of this sector of the sulcus. The majority of penetrations into the sulcus revealed coextensive auditory and visual activity, an observation apparently at variance with the identification of a purely visual field in this region. Barbiturate anaesthesia, which has been used in experiments demonstrating an anterior ectosylvian visual area, was found to have a depressing effect on auditory responses within the anterior ectosylvian sulcal field. PMID- 2262592 TI - Distribution of aromatase in the brain of the Japanese quail, ring dove, and zebra finch: an immunocytochemical study. AB - An immunocytochemical peroxidase-antiperoxidase procedure using a purified polyclonal antibody raised against human placental aromatase was used to localize aromatase-containing cells in the brain of three avian species: the Japanese quail, the ring dove, and the zebra finch. In quail and dove, immunoreactive cells were found only in the preoptic area and hypothalamus, with a high density of positive cells being present in the medial preoptic area, in the septal area above the anterior commissure, in the ventromedial nucleus of the hypothalamus, and in rostral part of the infundibulum. Immunoreactivity was weaker in zebra finches, and no signal could therefore be detected in the ventromedial and tuberal hypothalamus. The positive material was localized in the perikarya and in adjacent cytoplasmic processes, including the full length of axons always leaving a clear unstained cell nucleus. These features could be observed in more detail on sections cut from perfused brains and stained with an alkaline phosphatase procedure. The distribution of aromatase immunoreactivity was similar in the three species although minor differences were observed in the preoptic area. The localization of labelled neurons coincided with the distribution of aromatase activity as studied by in vitro radioenzyme assays on brain nuclei dissected by the Palkovits punch method. There was one striking exception to this rule: no immunoreactivity was detected in the zebra finch telencephalon, while assays had shown the presence of an active enzyme in several nuclei such as the robustus archistriatalis, the hyperstriatum ventrale pars caudale, and the hippocampus and area parahippocampalis. The origins of this discrepancy and the functional role of the aromatase observed in the axons are discussed. PMID- 2262594 TI - Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells. AB - This study deals with the site of origin, migration, and settling of the principal cell constituents of the rat hippocampus during the embryonic period. The results indicate that the hippocampal neuroepithelium consists of three morphogenetically discrete components--the Ammonic neuroepithelium, the primary dentate neuroepithelium, and the fimbrial glioepithelium--and that these are discrete sources of the large neurons of Ammon's horn, the smaller granular neurons of the dentate gyrus, and the glial cells of the fimbria. The putative Ammonic neuroepithelium is marked in short-survival thymidine radiograms by a high level of proliferative activity and evidence of interkinetic nuclear migration from day E16 until day E19. On days E16 and E17 a diffuse band of unlabeled cells forms outside the Ammonic neuroepithelium. These postmitotic cells are considered to be stratum radiatum and stratum oriens neurons, which are produced in large numbers as early as day E15. A cell-dense layer, the incipient stratum pyramidale, begins to form on day E18 and spindle-shaped cells can be traced to it from the Ammonic neuroepithelium. This migratory band increases in size for several days, then declines, and finally disappears by day E22. It is inferred that this migration contains the pyramidal cells of Ammon's horn that are produced mostly on days E17 through E20. The putative primary dentate neuroepithelium is distinguished from the Ammonic neuroepithelium during the early phases of embryonic development by its location, shape, and cellular dynamics. It is located around a ventricular indentation, the dentate notch, contains fewer mitotic cells near the lumen of the ventricle than the Ammonic neuroepithelium, and shows a different labeling pattern both in short-survival and sequential-survival thymidine radiograms. By day E18, the reduced primary dentate neuroepithelium is surrounded by an aggregate of proliferative cells; this is the secondary dentate matrix. On the subsequent days spindle-shaped cells that have retained their proliferative capacity migrate from the progressively receding secondary dentate matrix to the dentate gyrus itself. The latter, representing a tertiary germinal matrix, becomes highly active during the perinatal period. The putative fimbrial glioepithelium is situated between the primary dentate neuroepithelium and the tip of the hippocampal rudiment. Observations in methacrylate sections and thymidine radiograms suggest that the cells of this germinal matrix, unlike typical neuroepithelial cells, do not undergo interkinetic nuclear migration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2262595 TI - Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale. AB - In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22. Concordant with this is the observation that the hippocampal intermediate zone, which contains the sojourning young pyramidal cells, greatly enlarges between days E16 and E20, then suddenly diminishes and disappears by day E22. The other factor that may contribute to the prolonged sojourn of pyramidal cells, specifically those destined to settle in the CA1 region, is the pattern of alveolar channel development. This transient extracellular matrix begins to form several days after the onset of pyramidal cell neurogenesis, grows in a direction opposite to the settling of pyramidal cells in the stratum pyramidale, and does not reach the subicular end of Ammon's horn until day E21.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2262596 TI - Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. AB - Methacrylate-embedded sections and short-survival thymidine radiograms of the hippocampal dentate gyrus were examined in perinatal and postnatal rats in order to trace the site of origin and migration of the precursors of granule cells and study the morphogenesis of the granular layer. The densely packed, spindle-shaped cells of the secondary dentate matrix (a derivative of the primary dentate neuroepithelium) stream in a subpial position towards the granular layer of the internal dentate limb during the perinatal and early postnatal periods. By an accretionary process, the crest of the granular layer forms on day E21 and on the subsequent days the granular layer of the internal dentate limb expands progressively in a lateral direction. Granule cells differentiation, as judged by the transformation of polymorph, darkly staining small cells into rounder, lightly staining larger granule cells, follows the same gradient from the external dentate limb to the internal dentate limb. The secondary dentate matrix is in a process of dissolution by day P5. This matrix is the source of what will later become the outer shell of the granular layer composed of early generated granule cells. The thicker inner shell of the granular layer, formed during the infantile and juvenile periods, derives from an intrinsic, tertiary germinal matrix. On day E22, the dentate migration of the secondary dentate matrix becomes partitioned into two components: a) the subpial component of extradentate origin, referred to in this context as the first dentate migration, and b) the second dentate migration. The latter is distributed in the basal polymorph layer throughout the entire dentate gyrus and is henceforth recognized as the tertiary dentate matrix. The tertiary dentate matrix is prominent between days P3 and P10. It is postulated that the great increase in granule cell population during the infantile period is principally due to cells derived from this intrinsic matrix of the dentate gyrus. Between days P20 and P30 the tertiary dentate matrix disappears in the basal polymorph layer and henceforth proliferative cells become largely confined to the subgranular zone at the base of the granular layer. The subgranular zone is the source of granule cells produced during the juvenile and adult periods. PMID- 2262597 TI - Amacrine cells of the rhesus monkey retina. AB - Amacrine cells of the rhesus monkey, Macaca mulatta, were studied in 38 retinas Golgi-impregnated as whole, flat preparations. By using criteria of dendritic morphology, span of arborization, and level of arborization in the inner plexiform layer, 26 types of amacrine cell ranging in size of dendritic span from 30 microns to 2 mm were identified and listed in increasing size of dendritic span. In some instances, different cell types could be grouped together due to similar morphological features. For example, 1 group, "knotty amacrine cells," has small cell bodies and a profusion of small, varicose, intertwined processes that span up to 30 microns and are essentially monostratified, but each of the 3 types ends in different strata. Another group is 2 types with about 20 fine radiating processes spanning 1 mm that possess some prominent varicosities. One of these has all of its processes terminating in the innermost stratum of the inner plexiform layer ("spidery"-type 2 amacrine cells). The other with predominantly similarly ending processes has some that also terminate in the outermost stratum ("spidery"-type 1 amacrines). These 2 cell types likely correspond to the type 1 and type 2 indolamine-accumulating amacrine cells in rabbit retina. Other types are individuals which cannot be grouped together but resemble familiar types in cat retina (AII and A13). Other types can be correlated with their putative neurotransmitter (type 1 CA-dopamine) or transmitter/drug receptor ("spiny"-benzodiazepine receptor) phenotype. Many types as yet have no known correlate from other Golgi studies or clues as to transmitter or receptor phenotype. This study provides evidence for an unprecedented number of amacrine cell types in the primate retina. The similar morphologies of different types of amacrine cell types within a group suggest other common features within these groups such as neurotransmitter phenotype. PMID- 2262598 TI - Morphology of retinal ganglion cells in the flying fox (Pteropus scapulatus): a lucifer yellow investigation. AB - The morphology of retinal ganglion cells was determined in megachiroptera, commonly known as flying foxes. Retinal ganglion cells were intracellularly injected with the fluorescent dye Lucifer yellow in fixed retinae from adult little red flying foxes (Pteropus scapulatus) captured in their natural habitat. Ganglion cells closely resembled the three main classes of cat retinal ganglion cells, and therefore were classified into alpha-, beta-, and gamma-type cells. The size of the alpha- and beta-type somas and dendritic fields increased with increasing distance from the area centralis. However, this eccentricity dependence was not as pronounced as in the cat. The gamma-type cells were sub divided into mono-, bi-, and diffusely stratified, in accordance with the ramification of their dendrites within the inner plexiform layer. The alpha- and beta-type cells were uni-stratified in either the sublamina of the inner plexiform layer closest to the ganglion cell layer or in that closest to the inner nuclear layer. These laminae correspond to those in the cat retina which contain the dendritic ramifications of ganglion cells whose central receptive fields respond best to onset of light (the "on-centre" cells), or to ganglion cells whose centres respond optimally to light being extinguished (the "off centre" cells). Thus the flying fox retina contains a morphological correlate of the "on"/"off" dichotomy of alpha and beta cells in the cat retina. In general the flying fox retinal ganglion cells exhibit a degree of morphological complexity reminiscent of cat retinal cells and this may reflect similar functional properties. PMID- 2262599 TI - Distribution of parvalbumin immunoreactivity in the visual cortex of Old World monkeys and humans. AB - The macaque visual system has been frequently used as a model for understanding functional aspects of human vision. There are, however, few studies directly comparing biochemically defined neuronal populations in the visual cortex of the two species. In this study we compared the distribution and morphological features of the parvalbumin-immunoreactive neuronal subpopulation within humans and Old World monkeys (Macaca fascicularis and Macaca mulatta) by using monoclonal antibodies against the Ca2(+)-binding protein parvalbumin (PV), a neuronal marker in the vertebrate cerebral cortex. Characteristic laminar density and distribution of PV is observed, matching that seen with cytochrome C-oxidase and gamma-aminobutyric acid (GABA) immunoreactivity. Thus, parvalbumin is prominent in the layers receiving afferents from the dorsal lateral geniculate nucleus. Terminal fields are rich in layer IVA and IVC and moderate in the blob region of layer II-III of the monkey cortex. In the human visual cortex only layer IVC displays rich terminal fields. Parvalbumin is present in neurons within all layers of the cortex except layer I. Parvalbumin-immunoreactive (PV-ir) axons occur in different lamellae of the white matter containing axons belonging to association or projection neurons. The estimation of PV-ir neurons, determined for 50 microns-wide columns through the thickness of area 17, shows that the percentage of the total neuron number in area 17 of humans containing PV is 6.8 +/- 2.0%, and in the macaque monkey, 11.5 +/- 2.9%. The perikaryal area of PV-ir neurons varies according to the layer and is comparable in humans (109.3 +/- 40.8 microns2) and monkeys (94.3 +/- 29.5 microns2). However, the relative number of large PV-ir neurons is higher in humans. The immunoreactive product fills the thinnest cell processes and the shape of PV-ir neurons can be easily traced with the aid of a camera lucida. The shape of the neurons is similar in the two species studied, and they probably belong to non-spiny stellate, double-bouquet, chandelier, and basket cell classes. This study shows that parvalbumin acts as a marker for a subpopulation of interneurons in area 17, but it is also present in the geniculocortical as well as in corticocortical pathways. Moreover, the Old World monkey and human visual cortices have a similar, but not identical, distribution of this important calcium-binding protein. PMID- 2262600 TI - Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. AB - An antibody directed against protein kinase C (PKC) was applied to various mammalian retinae. In the cat, rat, rabbit, and macaque monkey we found PKC-like immunoreactivity in bipolar cells which had the morphology of rod bipolar cells; in the rat some amacrine cells were also immunoreactive. In the outer plexiform layer, labeled dendrites were always the central elements of the rod spherule invagination, and in the inner plexiform layer only rod bipolar axons and their axon terminals were immunoreactive. The antibody against PKC thus can be used to distinguish rod bipolar cells from cone bipolar cells. The antibody against PKC was used to determine the densities of rods and rod bipolar cells in the cat retina. In the central retina we found a rod to rod bipolar ratio of 16 to 1, in the periphery the ratio increases to 25 to 1. In freshly dissociated retina, cells with rod bipolar morphology could be identified; these cells were also labeled with the anti-PKC antibody. Hence, PKC-like immunoreactivity can be used to recognize rod bipolar cells in vitro. PMID- 2262601 TI - Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy. AB - The purpose of the present study was to describe the longitudinal and radial gradients of cochlear innervation in the cat. To this end, afferent and efferent terminals of both the inner (IHC) and outer hair cell (OHC) regions were reconstructed from serial ultrathin sections at six and eight cochlear locations, respectively, corresponding to roughly octave intervals of characteristic frequency (CF). Analysis of the afferent innervation of the IHCs showed 1) the number of radial fibers per IHC rises from 10 per IHC at the 0.25 kHz region to a maximum of 30 per IHC at the 10 kHz locus; 2) branching of radial fibers is essentially restricted to regions apical to the 1.0 kHz point; and 3) there are significant differences in synaptic-body morphology for synapses on different sides of the IHC, corresponding to known differences in afferent threshold and rate of spontaneous activity. With respect to efferent innervation in the IHC area, we found 1) that there were numerous vesicle-filled terminals contacting every IHC examined; however, those with obvious synaptic specialization were confined to the most apical regions; and 2) there were roughly the same numbers of efferent synapses per radial fiber at all cochlear locations; however, at each location, radial fibers contacting the modiolar side of the hair cell (corresponding to high-threshold afferents) showed significantly more efferent synapses than radial fibers contacting the pillar side. Analysis of the OHC afferent innervation showed 1) a clear rise in numbers of terminals per OHC from roughly 3 per cell in the base to 15 per cell in the apex, 2) no systematic differences in the numbers of terminals as a function of OHC row, and 3) that synaptic bodies at the OHC afferent synapse are common only apical to the 1.0 kHz locus. Counts of efferent terminals on OHCs revealed 1) maximal numbers (9 per OHC) between the 6 and 24 kHz regions and 2) striking decrease in terminal counts from first- to third-row OHCs. Ultrastructural data on efferent innervation were compared quantitatively with light-microscopic analysis of cochleas immunostained (with antibody to synaptophysin) to reveal all vesiculated terminals. PMID- 2262602 TI - Reorganization of cranial sympathetic pathways following neonatal ganglionectomy in the rat. AB - Postganglionic sympathetic innervation normally is distributed ipsilaterally to lateral cranial targets. However, contralateral outgrowth occurs following unilateral ganglionectomy in neonatal rats. This study was conducted to determine the prevalence, morphological features, ganglionic derivations, and temporal sequence of sympathetic reinnervation of denervated cranial targets. Unilateral superior cervical ganglionectomy of mature rats revealed exclusively ipsilateral distributions of catecholaminergic histofluorescent fibers to orbital targets (Meibomian gland, tarsal muscle, orbital muscle, iris, ciliary body, vasculature) and the circle of Willis, with the exception of the anterior cerebral artery. In mature rats following neonatal unilateral ganglionectomy, all targets were reinnervated by fibers displaying morphologies and target relationships similar to normal innervation, but with lower densities. Acute excision of the remaining superior cervical ganglion eliminated all fibers in 7 of 8 preparations. In adult rats receiving neonatal bilateral superior cervical ganglionectomies, cerebral vasculature was reinnervated consistently, and orbital targets contained fluorescent fibers in 6 of 16 cases, indicating that reinnervation can derive from other sources when superior ganglion outgrowth is prevented. Observations in developing rats revealed fibers along the cranial portion of the contralateral optic nerve sheath at 2-3 days postganglionectomy, and within the orbit at later ages, reaching the most distal targets by 14 days. It is concluded that widespread sympathetic reinnervation of orbital and cerebrovascular targets derives primarily from the contralateral superior ganglion. Orbital ingrowth apparently originates intracranially and enters the orbit by an atypical pathway within the optic foramen. PMID- 2262603 TI - Thymic innervation in the rat: a light and electron microscopical study. AB - The innervation of the rat thymus was studied by light and electron microscopy in juvenile and aged rats. By light microscopy numerous fine nerves were found in the connective tissue septa penetrating between the thymic lobules. These septa were clearly delineated in the juvenile animals, but indistinct in the aged rats, thus creating the spurious impression that thymic parenchyma contains nerves. In the aged animals the nerves are thicker, tortuous, and more branched than in juvenile animals. Electron microscopy confirms the light microscopic observations: no nerves were found within the thymic parenchyma. The thymic capsule and larger connective tissue septa contain bundles of myelinated and unmyelinated axons, surrounded by a perineural sheath. Within the extraparenchymal compartment, which is greatly enlarged in aged animals, efferent and sensory nerves, devoid of perineurium, were found to contact mainly reticular cells, and in rare instances plasma cells and lymphocytes. The majority of axonal varicosities are not closely related to cellular elements, and, in general, vesicles are relatively infrequent. The possible functional significance of these observations is discussed. PMID- 2262604 TI - Development of spinal neurons and tracts in the zebrafish embryo. AB - We have analyzed pathfinding by growth cones in the spinal cord of the early zebrafish embryo, because it is an extremely simple system. At 18-20 hours of development the spinal cord contains approximately 18 lateral and presumably post mitotic cell bodies per hemisegment. Of these 8-11 have projected growth cones by 18 hr of development and fall into five classes of neurons (Bernhardt et al., J. Comp. Neurol, preceding paper), including a set of mechanosensory (RB) neurons, three classes of interneurons (DoLA, ascending commissural, and VeLD), and previously characterized primary motor neurons (Eisen et al., '86: Nature 320:269 271). Of these five classes we analyzed pathfinding by the RB, DoLA, early ascending commissural, and VeLD neurons. These neurons are distinguishable at the earliest stages of axonogenesis based on the location of their somata and the number and initial directionality of their growth cones. In each case they follow stereotyped, cell-specific pathways to reach their termination sites. Up through larval stages exuberant axons have not been observed. The longitudinal axons of each neuronal class form bundles in the early cord. This apparently occurs because growth cones extend in close association with the longitudinal axons of the same neuronal class. At later stages spatially discrete commissural tracts are found in the cord suggesting that commissural growth cones may follow earlier commissural axons as well. PMID- 2262605 TI - Secure accommodation for very difficult adolescents: some recent research findings. AB - The appropriate use of secure accommodation for very difficult adolescents continues to cause concern. Research in the 1970s highlighted the variety of young people admitted to secure units and the difficulties of fashioning treatment programmes. As a result, gate-keeping and admission criteria have been tightened. Recent research has further clarified the needs and problems of young people in secure units and has highlighted the relationship between provision offered in child-care, penal and health services. New research findings, particularly those arising out of studies of young people in Youth Treatment Centres, are discussed in the light of these issues. PMID- 2262606 TI - Family economic stress, maternal and paternal support and adolescent distress. AB - The present study investigated the effects of family economic stress on parental support and adolescent maladjustment in 622 9th through 12th graders in a Midwestern farm community. Economic stress had a direct effect on adolescent depressive symptoms, delinquency and drug use. The findings also indicated an indirect effect: increased stress was associated with lower paternal support for female, but not male adolescents, and lower paternal support for females was associated with higher female distress. PMID- 2262607 TI - Health promotion for adolescents: preventive and corrective strategies against problem behavior. AB - This paper, in its first part, gives an overview of research on "problem behavior" in adolescence. Adolescence is considered to be a stage in life characterized by more experimentation, exploration, risk-taking, and rebellion than any other stages. Many health-damaging behaviors (drug consumption, precocious sexual activity, riskful driving, aggressive behavior, etc.) have important psychosocial functions in adolescents' developments. Some of these behaviors can be signals of "stress", defined as a bio-psycho-social state of tension resulting from a variety of stressors which confront adolescents daily in modern industrial societies. In the second part of the paper, the implications of this research for strategies of intervention are discussed. The systematic analysis distinguishes between different stages in the process by which problem behavior emerges and separates "preventive" from "corrective" forms of intervention. Additionally, the analysis differentiates between the dimensions targeted by the measures: interventions addressed toward individual behavior ("personal resources") on the one hand, and living conditions ("social resources") on the other hand. The resulting types of intervention approaches are illustrated with examples and discussed in view of how appropriate they are for health promotion in adolescence. Implications for "social policy for adolescents" are discussed. PMID- 2262608 TI - Identity status and self-construct systems: process X structure interactions. AB - This study investigated the relationship between identity status and structural dimensions of individuals' self-theories or personal construct systems. The sample was composed of 31 Achievers, 31 Moratoriums, 30 Foreclosures, and 26 Diffusions. Participants completed a modified version of Kelly's (1955) Role Construct Repertory test designed to assess their personal sense of integrative continuity over time. Status differences in self-construct differentiation, integration, and self-certainty were analyzed. Results indicated that Moratoriums and Diffusions had the highest self-construct differentiation. Achievers were the most self-certain in their ratings, Diffusions the least. Status differences in self-theory integration were found, but only when a qualitative, structural analysis of levels of self-construct differentiation and integration was performed. No sex effects were found. Results are discussed as replicating and extending previous work in the area, and future research directions are noted. PMID- 2262609 TI - An outpatient treatment alternative for suicidal youth. AB - The present study demonstrates the safety and effectiveness of an outpatient treatment program for suicidal children and adolescents. Pre- and post-treatment measures of patient behavior and family functioning are presented for 47 adolescents and latency-aged children who received treatment from the Systemic Crisis Intervention Program at the Houston Child Guidance Center. Follow-up was conducted at three and six months and at a point between 12-18 months. All measures indicated significant long-term improvement. Data concerning post institutional use and suicidal behavior are also presented. PMID- 2262610 TI - Relations among early adolescent temperament, parent and peer demands, and adjustment: a test of the goodness of fit model. AB - This study assessed whether the goodness of fit--between early adolescents temperaments and their parents and peers demands, or "ethnotheories", regarding temperament--was more related to adjustment than were acontextual measures of temperament alone. Data from the Pennsylvania Early Adolescent Transitions Study, a short-term longitudinal investigation of 153 adolescents from the beginning of sixth grade to the end of seventh grade, were used. Temperament was indexed by the nine attributes measured by the Revised Dimension of Temperament Survey, and the measures of demands regarding temperament were derived from different versions of this instrument. Adjustment was indexed by teacher ratings of academic and social competence and by parent ratings of problem behaviors. At the end of Grade 6 and the beginning of Grade 7, the number of significant relations between the adjustment measures and the fit scores tended to be greater than the number of significant relations between adjustment and temperament, measured alone. Moreover, groups formed on the basis of high vs. low temperament fit showed differential adjustment scores: adolescents in the low fit group in regard to both peer- and parent-demands received lower teacher ratings of scholastic competence, and higher parent ratings for conduct and school problems, than did the adolescents in the high fit group. PMID- 2262611 TI - The measurement of adolescent adaptive processes in the clinical interview. AB - A study is described measuring the clinical usefulness of Adolescent Adaptive Process Scales. These processes are measured in three groups of adolescents in which psychopathology is also measured using a standardized psychiatric interview. Inter-rater reliability is calculated between two raters and mean score comparisons are made between the groups using the t-test method. In the study a higher inter-rater reliability and some preliminary evidence of construct validity are found for these scales. The findings indicate that these scales could constitute a useful clinical tool in psychotherapy, research and teaching. They also provide scope for future work in the field. PMID- 2262612 TI - Dual publication and manipulation of the editorial process. PMID- 2262613 TI - The history of liposculpture. PMID- 2262614 TI - Liposculpture: the "correct" history of liposuction. Part I. PMID- 2262615 TI - A superior method of tattoo removal using the Q-switched ruby laser. AB - The Q-switched ruby laser was used to treat 101 amateur and 62 professional tattoos in 80 patients over a period of 22 months. Using a 5- to 8-mm spot size and energy fluences of 2-4 joules/cm2, an average of three retreatments resulted in complete pigment removal in four, nearly complete pigment removal in 84, significant pigment removal in 11, and minimal pigment removal in two amateur tattoos. Using identical parameters for professional tattoos, there was complete pigment removal in two, nearly complete pigment removal in five, significant pigment removal in 18, minimal pigment removal in 25, and very little pigment removal in 12. Professional tattoos with red, yellow, and green pigments faded, but required multiple retreatments. While transient hypopigmentation occurred in many patients, skin texture and hair growth returned to normal in all cases and no hypertrophic scarring was seen. PMID- 2262616 TI - The universal liposuction cannula handle modifier. PMID- 2262617 TI - Cartilage removal prior to skin grafting in the triangular fossa, antihelix, and concha of the ear. AB - Skin grafting onto a large area of exposed ear cartilage with irregular contours poses an increased risk of inadequate re-establishment of circulation. Removal of cartilage not needed for structural support before grafting following Mohs surgery on the triangular fossa, antihelix, and concha of the ear decreases the risk of recurrence of the carcinoma, and increases the chances for survival of the graft. PMID- 2262618 TI - HIV and the dermatologic surgeon. PMID- 2262619 TI - Mohs micrographic surgery fixed-tissue technique for melanoma of the nose. AB - Mohs micrographic surgery, fixed-tissue technique, for excision of nasal melanoma provides three important benefits: 1) assurance of eradication of the main mass along with its "silent" contiguous outgrowths, 2) safe management of non contiguous satellites too small to be visible initially, and 3) safe sparing of maximal amounts of surrounding normal tissues. These benefits are achieved because all incisions are through chemically fixed (killed) tissue, eliminating the danger of disseminating the highly transplantable melanoma cells and permitting the excision of successive layers for microscopic scanning of their undersurfaces by the systematic use of frozen sections. The process is continued to the termination of each ramification. There is no need to remove a wide margin of normal tissue as is customary with conventional surgery. Clinically invisible satellites are not moved or disturbed and can be removed safely by the same method if they appear. The reliability of the method is manifested by the 62.5% 5 year cure in a series of 10 consecutive patients, all of whom had no local recurrence after micrographic surgery. PMID- 2262620 TI - Razor-blade surgery. AB - The razor blade can be a valuable tool in the performance of many minor surgical procedures. It is extremely sharp, flexible, inexpensive, readily available, and easy to use. The technique and specific applications are reviewed and discussed. PMID- 2262621 TI - Fine-needle aspiration for diagnosis of intranodal squamous-cell carcinoma metastatic from the skin. AB - Fine-needle aspiration is a useful way to determine the presence of squamous-cell carcinoma in enlarged lymph nodes of patients at high risk for metastases. Advantages include a high degree of accuracy, outpatient as well as inpatient availability, and negligible potential for seeding of malignant cells. Cutaneous oncologists should consider using this technique in patients with lymphadenopathy and a previous history of cutaneous squamous cell carcinoma. PMID- 2262622 TI - Systemic isotretinoin: effects on dermal wound healing in a rabbit ear model in vivo. AB - Clinical observations have suggested that wound healing may be altered in patients treated with systemic isotretinoin. In this study, we examined the effects of systemic isotretinoin on dermal wound healing and connective tissue metabolism in a rabbit ear model. Forty 6-mm punch-biopsy wounds were created in the ears of two control rabbits as well as two experimental animals fed isotretinoin, 4 mg/kg per day. Clinical inspection and histologic examination revealed no difference between the control and isotretinoin-treated rabbits in terms of the time required for complete wound healing or the appearance of the final scar. The tissue removed from the wound site at days 0, 7, 14, and 21 after wounding was subjected to analysis of a collagen production and collagen gene expression. Collagen production, determined by the synthesis of [3H]hydroxyproline after incubation of tissue slices with [3H]proline in vitro or by the measurement of the steady-state levels of types I and III procollagen mRNAs, was not significantly different between the two groups. The results indicate that systemic administration of isotretinoin does not affect collagen synthesis in the rabbit ear model of wound healing. PMID- 2262623 TI - Quantitative assessment of augmentation therapy. AB - We report the results obtained from 18 women whose facial folds and furrows were treated with augmentation therapy. The results of treatment with microlipoinjection and injectable collagen were measured and compared at regular intervals for a period of 1 year using a method of optical profilometry. Subsidence was noted with both modalities. Collagen gave consistent results. Seventy-five percent of correction on the average is lost at 6 months, but 22% of the collagen-treated subjects maintained at least 30% correction 1 year from the time of treatment. Autologous fat gave unpredictable results ranging from poor to excellent. A good result at 6 months is likely to be maintained until 1 year from the time of treatment. Forty-four percent of fat augmented subjects maintained at least 30% correction 1 year after treatment. PMID- 2262624 TI - Basal cell carcinoma arising in pemphigus vulgaris of the lower eyelid. AB - A 59-year-old woman on continuous treatment with corticosteroids and immunosuppressive drugs for pemphigus vulgaris of 14 year's duration presented with an enlarging nodular lesion on the right lower eyelid. The neoplasm, diagnosed as basal cell carcinoma, was excised conserving the lid margin, and eyelid reconstruction was done with a rotated cheek flap. Wound healing proceeded without complications in spite of immunosuppressive treatment, and the final cosmetic and functional result was satisfactory. PMID- 2262625 TI - A novel method for the measurement of acoustic speed. AB - Traditional methods for measuring acoustic speed require knowledge of either the specimen thickness or the distances between the transducers and the specimen. In general, the accuracy in measuring these quantities determines the accuracy of the experimental technique for measuring speed. This problem is particularly acute in measuring sound speed in biological specimens. A new method for measuring acoustic speed of materials, which eliminates the need for determining these quantities, has been developed. The technique, which necessitates the use of only one transducer, requires measurement of four times of flight of a sound pulse and the knowledge of the speed of sound in a reference fluid medium in which the specimen is placed. Ultrasonic speed in stainless steel and Plexiglas was measured using this method to verify its validity. Results on measurements on porcine liver, myocardium, and soft fat are also reported. PMID- 2262626 TI - Some factors affecting the magnitude of comodulation masking release. AB - This paper examines some of the factors that can affect the magnitude of comodulation masking release (CMR). In experiment I, psychometric functions were measured for the detection of a 1-kHz sinusoidal signal in a "multiplied" narrow band noise centered at 1 kHz (reference condition) and the same noise with two comodulated flanking bands added. The functions were slightly steeper for the comodulated than for the reference masker. Thus CMRs measured at a high percent correct point were slightly (0.4 dB) larger than CMRs measured at a low percent correct point. Large individual differences were found for the reference masker but not for the comodulated masker. Experiment II compared CMRs obtained with narrow-band Gaussian noise and multiplied noise, using a single flanking band. For a flanking band remote from the signal frequency, the CMRs were smaller and more variable for the multiplied noise than for the Gaussian noise. This variability arose mainly from individual differences in the reference condition. Experiment III compared growth-of-masking functions for a signal centered in Gaussian noise and multiplied noise. Thresholds were lower for the multiplied than for the Gaussian noise, and the differences were greatest at high noise levels. The results are consistent with the idea that, for multiplied noise, some subjects can detect a change in the distribution of the envelope of the stimulus, when the signal is added to the masker. Such subjects have low thresholds in the reference condition, and give small CMRs. Other subjects are relatively insensitive to this cue. They have higher thresholds in the reference condition, and give larger CMRs. For Gaussian noise, thresholds for the reference condition are relatively stable across subjects and CMRs tend to be substantial, even for flanking-band frequencies remote from the signal frequency. PMID- 2262627 TI - Spectro-temporal integration in signal detection. AB - This paper is concerned with aspects of temporal integration and across-frequency integration in signal detection. Previous experiments on the detection of brief broadband signals (clicks) in continuous broadband noise revealed efficient spectral integration. The extent to which this effect is restricted to a critical time window was investigated by manipulating the temporal relations among the signal components in different frequency regions. In a typical experiment, the signal consists of nine brief Gaussian-shaped tone pulses, equally distributed at 1/3-oct intervals, each with a spectral width of about 1/3 oct, and each equally detectable in white noise. In the synchronized condition (i.e. coinciding peaks of the nine Gaussian envelopes), the detection threshold is reached when the levels of the nine individual tone pulses are about 8 dB below their individual threshold levels (efficient spectral integration). When the signal is progressively desynchronized (i.e. noncoinciding peaks of the Gaussian envelopes), detection threshold is found to increase. This suggests that efficient spectral integration in signal detection is confined to a narrow time window, with a typical value of 30 ms. Similar experiments were performed with respect to the efficiency of temporal integration. For constant-duration signals (100 ms), the detection threshold is found to increase when progressively widening signal bandwidth. The data indicate that the efficient temporal integration in signal detection is confined to a narrow frequency window, which, not surprisingly, corresponds to the critical bandwidth. PMID- 2262628 TI - Hearing a mistuned harmonic in an otherwise periodic complex tone. AB - The ability of a listener to detect a mistuned harmonic in an otherwise periodic tone is representative of the capacity to segregate auditory entities on the basis of steady-state signal cues. By use of a task in which listeners matched the pitch of a mistuned harmonic, this ability has been studied, in order to find dependences on mistuned harmonic number, fundamental frequency, signal level, and signal duration. The results considerably augment the data previously obtained from discrimination experiments and from experiments in which listeners counted apparent sources. Although previous work has emphasized the role of spectral resolution in the segregation process, the present work suggests that neural synchrony is an important consideration; our data show that listeners lose the ability to segregate mistuned harmonics at high frequencies where synchronous neural firing vanishes. The functional form of this loss is insensitive to the spacing of the harmonics. The matching experiment also permits the measurement of the pitches of mistuned harmonics. The data exhibit shifts of a form that argues against models of pitch shifts that are based entirely upon partial masking. PMID- 2262629 TI - Effects of fluctuating noise and interfering speech on the speech-reception threshold for impaired and normal hearing. AB - The speech-reception threshold (SRT) for sentences presented in a fluctuating interfering background sound of 80 dBA SPL is measured for 20 normal-hearing listeners and 20 listeners with sensorineural hearing impairment. The interfering sounds range from steady-state noise, via modulated noise, to a single competing voice. Two voices are used, one male and one female, and the spectrum of the masker is shaped according to these voices. For both voices, the SRT is measured as well in noise spectrally shaped according to the target voice as shaped according to the other voice. The results show that, for normal-hearing listeners, the SRT for sentences in modulated noise is 4-6 dB lower than for steady-state noise; for sentences masked by a competing voice, this difference is 6-8 dB. For listeners with moderate sensorineural hearing loss, elevated thresholds are obtained without an appreciable effect of masker fluctuations. The implications of these results for estimating a hearing handicap in everyday conditions are discussed. By using the articulation index (AI), it is shown that hearing-impaired individuals perform poorer than suggested by the loss of audibility for some parts of the speech signal. Finally, three mechanisms are discussed that contribute to the absence of unmasking by masker fluctuations in hearing-impaired listeners. The low sensation level at which the impaired listeners receive the masker seems a major determinant. The second and third factors are: reduced temporal resolution and a reduction in comodulation masking release, respectively. PMID- 2262630 TI - Binaural masking experiments using noise maskers with frequency-dependent interaural phase differences. I: Influence of signal and masker duration. AB - In this paper previous experiments on auditory filter shapes in binaural masking experiments [A. Kohlrausch, J. Acoust. Soc. Am. 84, 573-583 (1988)] are extended to a wider range of masker and signal durations. The masker was a dichotic broadband noise with frequency-dependent interaural parameters. The interaural phase difference of the masker was 0 below 500 Hz and pi above 500 Hz. Signal frequency varied between 200 and 800 Hz, and the signal was presented either monaurally (Sm) or binaurally in antiphase (S pi). In the first experiment, the masker duration was fixed at 500 ms and signals of 250 and 20 ms were used. In the second experiment, the signal duration was fixed at 20 ms, and the masker duration was reduced to 25 ms. The results from both experiments are consistent with studies using No or N pi maskers: The binaural masking level difference (BMLD) increases slightly for shorter test signals and decreases strongly for short maskers. The BMLD patterns of the first experiment are well described by the auditory-filter model derived for stationary test signals, if the additional influence of "off-frequency listening" for the short test signal is taken into account. The BMLDs resulting from the second experiment (25-ms masker), however, are much lower than predicted by this filter model This outcome supports previous observations that binaural unmasking becomes less effective for very short masker durations and indicates that this effect is even stronger for maskers with a complex structure of interaural parameters. PMID- 2262631 TI - Binaural masking experiments using noise maskers with frequency-dependent interaural phase differences. II: Influence of frequency and interaural-phase uncertainty. AB - This study investigates whether binaural signal detection is improved by the listener's previous knowledge about the interaural phase relations of masker and test signal. Binaural masked thresholds were measured for a 500-ms dichotic noise masker that had an interaural phase difference of 0 below 500 Hz and of pi above 500 Hz. The thresholds for two difference 20-ms test signals were determined within the same measurement using an interleaved adaptive 3-interval forced choice (3IFC) procedure. In each 3IFC trial, both signals could occur with equal probability (uncertainty). The two signals differed in frequency and interaural phase in such a way that one signal always had a frequency above the masker edge frequency (500 Hz) and no interaural phase difference (So), whereas the other signal frequency was below 500 Hz and the interaural phase difference was pi (S pi). The frequencies of a signal pair remained fixed during the whole 3IFC track. These two signals thus lead to two different binaural conditions, i.e., NoS pi for the low-frequency signal and N pi So for the high-frequency signal. For comparison, binaural masked thresholds were measured with the same masker for fixed signal frequency and phase. The binaural masking level differences (BMLDs) resulting from the two experimental conditions show no significant difference. This indicates that the binaural system is able to apply different internal transformations or processing strategies simultaneously in different critical bands and even within the same critical band. PMID- 2262632 TI - Active localization of virtual sounds. AB - A simple virtual sound display built around a microcomputer and analog hardware is described. The display implements most of the primary cues for sound localization in the ear-level plane. Judging both from informal observations by users and from objective data obtained in an experiment on homing to virtual and real sounds, it is concluded that simple displays like the one described are effective in creating the impression of external sounds to which observers can locomote with ease; in particular, this means that simulation of the direction dependent spectral shaping effects of the pinnae is not a necessary requirement for extracranial sound localization. PMID- 2262633 TI - Revision of estimates of acoustic energy reflectance at the human eardrum. AB - An improved analysis procedure has been applied to standing wave patterns measured previously [B. W. Lawton and M. R. Stinson, J. Acoust. Soc. Am. 79, 1003 1009 (1986)] in human ear canals. Revised acoustic energy reflection coefficients, at the eardrum, are obtained for 20 ears for frequencies between 3 and 13 kHz. The new analysis addresses anomalous features of the standing wave patterns, apparent at frequencies above 8 kHz, due primarily to the curvature of the ear canal. Much better agreement is now found, at these higher frequencies, between the theoretical form assumed for the standing wave patterns and the experimental data. The revised values of eardrum reflectance are somewhat smaller, especially for frequencies above 11 kHz. The reflectance rises from about 0.25 at 4 kHz up to 0.7 at 8 kHz, falls to a minimum of 0.5 at 11 kHz, then rises to 0.6 at 13 kHz. Considerable intersubject variability in the results is noted. PMID- 2262634 TI - Amplitude and frequency fluctuations of spontaneous otoacoustic emissions. AB - Amplitude and frequency fluctuations of spontaneous otoacoustic emissions have been studied. Spontaneous otoacoustic emissions were recorded from eight human ears and two frog ears (Rana esculenta). Record length typically was 80 s. For a recorded emission signal, the amplitude signal A(t) (average A0) and time intervals T(ti) between successive positive-going zero crossings (i counts zero crossings) were determined. Emission amplitude and period both showed small fluctuations: delta Arms/A0 ranged from 0.7 X 10(-2) to 6.3 X 10(-2) for human emissions and was 24 X 10(-2) for both frog emissions; delta Trms ranged from 1.4 to 6.9 X 10(-7) s for human emission and was 50.0 and 55.0 X 10(-7) s for the two frog emissions. There was a positive correlation between delta Arms/A0 and delta Trms as determined for different emissions (R = 0.9). Spectra of A(t) and T(ti) revealed that amplitude and period were slowly fluctuating functions: cutoff frequency delta f delta A of the amplitude spectrum ranged from 3 to 18 Hz; delta f delta T ranged from 7 to 32 Hz. Results have been compared to amplitude and frequency fluctuations of a second-order oscillator, that interacts with a noise source. It has been concluded that an oscillator with linear stiffness (for example a Van der Pol oscillator) driven by white Gaussian noise, cannot account for all experimental results. Other possible oscillators (e.g., nonlinear stiffness) and noise sources (e.g., narrow-band noise), that may account for the observed phenomena, are discussed. PMID- 2262635 TI - What type of force does the cochlear amplifier produce? AB - Recent experimental measurements suggest that the mechanical displacement of the basilar membrane (BM) near threshold in a viable mammalian cochlea is greater than 10(-8) cm, for a stimulus sound-pressure level at the eardrum of 20 microPa. The associated response peak is very sensitive to the physiological condition of the cochlea. In the formulation of all recent cochlear models, it has been explicitly assumed that this peak is produced by the cochlear amplifier injecting a large amount of energy into the cochlea, thereby altering the real component of the BM impedance. In this paper, a new cochlear model is described which produces a realistic response by assuming that the cochlear amplifier force acts at a phase such that the main effect is to reduce the imaginary component of the BM impedance. In this new model, the magnitude of the cochlear amplifier force required to produce a realistic response is much smaller than in the previous models. It is suggested that future experimental investigations should attempt to determine both the magnitude and the phase of the forces associated with the cochlear amplifier. PMID- 2262636 TI - Radiation and vibrational properties of submerged stiffened cylindrical shells. AB - The vibratory response of submerged cylindrical shells is investigated. The shell response is presented in terms of the spatial wave-number spectrum of the normal surface displacement. The power output of the vibrating shell into the fluid and the far-field radiation from the shell are presented as a function of the wave number of the exciting force. The effects of structural damping and stiffeners are also studied. PMID- 2262637 TI - Acoustic streaming in a rotating fluid. AB - Acoustic streaming theory is derived that is applicable to a fluid that is slow moving in a reference frame that rotates with a constant angular velocity omega. A simplified streaming equation is obtained for the special case in which the acoustic angular frequency omega is large relative to omega, and the change in fluid density due to rotation alone is negligible. For this special case it is shown that the "driving force" for the acoustic streaming is independent of omega. Thus, if no acoustic streaming is present in a fluid system that is stationary, then no steady-state acoustic streaming is predicted for a similar system that rotates with constant angular velocity. For a system in which acoustic streaming is present, the flow behavior depends on the relative magnitudes of the Coriolis forces and the viscous forces. If the Ekman number is large (that is, the viscous force dominates) then the predicted flow is identical to that which would exist in a stationary system. If, on the other hand, the Ekman number is small then the Coriolis force dominates and the component of flow in the direction of the axis of rotation can be much smaller in the rotating system than in a similar system at rest. PMID- 2262638 TI - A new integral equation formulation for an axisymmetric structure. AB - A new method is developed to compute the acoustic field outside an axisymmetric structure from the normal velocity values on the surface. Surface pressure and normal velocity are expanded in a series of functions that are orthonormal on the surface of the structure and have a constant ratio of pressure to normal derivative of pressure at vanishing frequency. The Helmholtz integral equation is next used to compute the field everywhere outside the structure. The method is tested by applying it to scattering from a rigid cylinder with hemispherical endcaps. The series is shown to converge very rapidly. PMID- 2262639 TI - A note on hidden factors in vowel perception experiments. PMID- 2262640 TI - Nasal polyposis. PMID- 2262641 TI - Interleukin-1 is released at sites of human cutaneous allergic reactions. AB - Interleukin-1 (IL-1) promotes cell recruitment and influences allergic mediator release. We analyzed histamine, prostaglandin D2, IL-1, and leukocytes accumulating hourly for 12 hours at skin-chamber sites after local ragweed challenge in eight allergic subjects with cutaneous late-phase reactions. Ragweed induced a peak of histamine at 1 hour (p less than 0.02), which diminished, and then steadily increased (p less than 0.02). Prostaglandin D2 levels peaked by the second hour (p less than 0.02) and then decreased, approaching prechallenge levels by 12 hours. Leukocyte infiltration (predominantly neutrophils) was detectable 3 to 4 hours after challenge, although selective enrichment of mononuclear cells, eosinophils, and basophils ws observed at later hours (p less than 0.02). IL-1 bioactivity was detected in fluids 10 to 12 hours after challenge but not at control sites (p less than 0.05). Analysis of IL-1 beta levels by RIA revealed an initial peak at 1 hour of 0.90 ng/ml (p less than 0.02) and a second elevation of up to 0.75 ng/ml during the later hours (p less than 0.04). Ragweed challenge of three nonatopic subjects did not change levels of the above-mentioned mediators or cells. Bioactivity in chamber fluids from antigen challenged sites of atopic subjects was significantly neutralized by an anti-IL-1 beta antiserum, although treatment with anti-IL-1 alpha and anti-IL-1 beta was needed for complete neutralization, IL-1 released locally during cutaneous allergic reactions may contribute to IgE-dependent cutaneous inflammation. PMID- 2262642 TI - Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells. AB - We challenge each of 55 consecutive ragweed (RW)-allergic patients with hay fever and with graded increasing doses of ragweed extract to investigate the frequency and relationship between the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge. We evaluated the nasal response by measuring the levels of histamine, TAME-esterase activity, and kinins in the nasal lavage fluid and by grading symptoms. Fifty-one subjects (92.7%) had an ER consisting of a dose-dependent, concommitant increase in both mediators and symptoms. The total amount of TAME-esterase activity and kinins generated during ER correlated significantly with specific serum IgE (ssIgE), intradermal skin test (ST) sensitivity, and basophil histamine release (BHR) to antigen E (p less than 0.01 for each). Twenty-four (47%) subjects developed a late increase in mediators and 23 (45%) subjects in symptoms. None of the four subjects without an ER developed an LPR. The levels of the late-appearing mediators were not predicted by ST, ssIgE, or BHR. There was a significant but weak association between the intensity of ER and LPR, but there was no significant difference in the IgE antibodies, ST, BHR, and intensity or threshold of ER between dual and early only reactors. The number of eosinophils and neutrophils in the LPR lavages increased over the prechallenge baseline, and their numbers correlated (p less than 0.05) with ER kinins (r = 0.46, and 0.37, respectively), ER TAME-esterase activity (r = 0.28 and 0.24, respectively), and in the case of eosinophils, ER histamine (r = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262643 TI - Allergen dose response and late symptoms in a human model of ocular allergy. AB - Eleven ryegrass-sensitive patients were challenged weekly for 4 weeks with incremental doses of ryegrass allergen applied topically to one eye; a buffer was applied to the other eye. A clinical examination and tear-fluid cytology were performed before challenge and at 20 minutes, 1 hour, and 6 hours after challenge. A significant clinical reaction and neutrophil accumulation in the tear film occurred at 20 minutes. At 1 hour, a clinical response and tear cytologic reaction were present only at higher antigen concentrations. Six hours after antigen challenge, only the highest allergen concentration (320,000 BU/ml) produced a clinical late-phase reaction (LPR) (p less than 0.01) and tear cytologic change (presence of eosinophils and lymphocytes). Five nonryegrass sensitive control subjects were unresponsive to a similar challenge. These results indicate that a conjunctival response to allergen challenge is dose dependent, that is, the higher the dose, the more likely an LPR will occur and that an LPR correlates with significant numbers of inflammatory cells in the tear film. PMID- 2262644 TI - Elevated serum concentrations of IgE antibodies to environmental antigens in HIV seropositive male homosexuals. AB - Forty-five homosexual male subjects with human immunodeficiency virus (HIV) infection, who received care during a 4-month period in an ambulatory center for acquired immunodeficiency syndrome (AIDS), were classified according to their principal presentation with characteristic secondary infections (CDC group IV C, N = 28), cancers (IV D, N = 10), or limited or no symptoms (groups II, III, IV A, or IV B, N = 7). The incidence of allergic rhinitis and conjunctivitis increased after HIV seroconversion by approximately twofold in patients of groups IV C and IV D. The mean serum concentration of IgE was significantly higher for group IV C than for the other HIV-seropositive groups and for a control group of 45 HIV seronegative homosexual male subjects from the same community who were studied concurrently. More patients in groups IV C and IV D had positive RASTs for a panel of environmental antigens than patients in the other HIV-seropositive groups and the HIV-seronegative control group. Patients with AIDS presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases. PMID- 2262645 TI - Allergy to different fish species in cod-allergic children: in vivo and in vitro studies. AB - The presence of a positive clinical history and skin test (ST) results for 17 fish species (anchovy, bass, carp, dogfish, eel, gilthead, mackerel, mullet, perch, red mullet, salmon, sardine, sole, tench, toothed gilthead, trout, and tuna) were investigated in 20 children with cod-positive clinical history, ST, and RAST, and in 40 children positive to one or more foods different from cod (cow's milk, chicken egg white, peanut, and tomato). In cod-positive children, positive clinical history (60%) and ST (85%) to fish species were more frequent than in cod-negative children (7.5% and 10% respectively). In cod-positive children, a high frequency of positive STs to eel (85%) and to bass, dentex, sole, and tuna (55%) was observed. Positivity to dogfish (10%) was the least frequent. RAST-inhibition experiments suggested the presence of cross-reacting antigen(s) in cod, bass, dentex, eel, sole, and tuna. Results of this study demonstrate that cod allergy might be, on the whole, a reliable index of fish allergy, but cod-positive children may perhaps tolerate some other species, which will have to be tested for possible inclusion in their diet. PMID- 2262647 TI - Physiologic responses to intranasal dose-response challenges with histamine, methacholine, bradykinin, and prostaglandin in adult volunteers with and without nasal allergy. AB - The dose-response (dose, 0.01, 0.05, 0.1, 0.5, 1, and 5 mg) profiles of 10 atopic and 10 nonatopic subjects were determined for nasal patency, secretion weight, pulmonary function, eustachian tube function, middle-ear function, and symptoms after intranasal inhalation challenges with histamine, bradykinin, methacholine, prostaglandin D2, and prostaglandin F2 alpha (PGF2 alpha). Results demonstrated that challenge with PGF2 alpha increased nasal patency, whereas challenge with all other substances decreased patency. The relationship between substances in eliciting a nasal congestive response was prostaglandin D2 greater than histamine greater than bradykinin greater than methacholine. A similar effect ordering was noted for the postchallenge development of eustachian tube dysfunction. Secretion weights were significantly greater after challenge with histamine compared to all other substances. A decrease in pulmonary function was observed only after challenge with PGF2 alpha, although the effect was not statistically significant. No changes in middle-ear pressure were observed for challenges with any of the substances. Only histamine challenge provoked sneezing, whereas challenge with either of the prostaglandins provoked cough. With the exception of methacholine, all substances caused symptoms of rhinorrhea, congestion, and sore throat. Bradykinin was particularly effective in provoking "pain/pressure"-related symptoms. With the exception of secretion weight, the differences between responses of atopic and nonatopic subjects were not statistically significant. These results document mediator specificity in the physiologic and symptomatic responses to intranasal challenge. PMID- 2262646 TI - Comparison of the effects of inhaled corticosteroids on the airway response to histamine, methacholine, hyperventilation, and sulfur dioxide in subjects with asthma. AB - To investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli, we studied 25 subjects with mild asthma with a double-blind, noncrossover design to compare the effect of a 3-week treatment with salbutamol (0.2 mg, four times a day [q.i.d.]) and placebo (N = 11) to the effect of salbutamol (0.2 mg q.i.d.) and inhaled beclomethasone dipropionate (BDP, 0.5 mg q.i.d.) (N = 14). Airway response to histamine and methacholine was assessed as the provocative concentration (in milligrams per milliliter) necessary to increase the specific airway resistance (SRaw) (in centimeters of H2O times second) by 100% (PC100 SRaw). Airway response to hyperventilation of air and to hyperventilation of 0.75 ppm of sulfur dioxide (SO2) was determined as the provocative ventilation (in liters per minute) necessary to increase SRaw by 75% (PV75 SRaw). Challenges were performed on separate days before and after treatment, and salbutamol inhalation was withheld at least 6 hours before each challenge. Salbutamol and placebo did not change perchallenge baseline SRaw nor did they have any significant effect on the airway response to the stimuli. Salbutamol and BDP decreased the mean prechallenge baseline SRaw (SEM) from 7.7 (0.37) to 5.9 (0.28) (p less than 0.01) and significantly (p less than 0.01) increased geometric mean (SEM) PC100 SRaw for histamine from 0.5 (1.42) to 0.9 (1.53) mg/ml; for methacholine, from 0.2 (1.47) to 0.5 (1.51) mg/ml; and mean (SEM) PV75 SRaw for hyperventilation of air from 51.8 (2.32) to 58.4 (1.86) L/min. In contrast, the change of PV75 SRaw during hyperventilation of SO2 from 26.2 (2.29) to 31.4 (3.30) L/min was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262648 TI - Identification and purification of an important cross-reactive allergen from American (Periplaneta americana) and German (Blattella germanica) cockroach. AB - Aqueous whole body extracts from two major domiciliary cockroaches, the American, Periplaneta americana, and the German, Blattella germanica, were analyzed in crossed immunoelectrophoresis and immunoblotting. Forty-five antigens were found in P. americana and 29 in B. germanica. IgE-binding antigens were identified by crossed radioimmunoelectrophoresis with sera from 30 cockroach-allergic patients. Seven and three precipitates from P. americana and B. germanica bound significant amounts of IgE. A cross-reactive, apparently homologous allergen, from P. americana and B. germanica bound IgE from 100% and 70%, respectively, of the patients. These important allergens were tentatively named Per a I and Bla g I. The allergens were purified by sequential ion exchange, gel filtration, and isoelectric focusing. Both allergens had a molecular size of 33 to 37 kd in Sephadex G-75 gel filtration, and 28 kd in high-performance liquid chromatography gel filtration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a minor band at approximately 25 kd, and most of the protein at 6 kd. The isoelectric point of both allergens was found be to 3.5. In amino acid analysis, the allergens were highly similar. Skin test revealed the allergens to be important in vivo sensitizing agents. The allergens may be used for environmental assays for cockroach exposure in the homes of allergic subjects. PMID- 2262649 TI - A double-blind comparison of intranasal budesonide with placebo for nasal polyposis. AB - Intranasal budesonide, 400 micrograms two times a day, was evaluated in 36 patients referred for treatment of nasal polyposis. The age range was 20 to 68 years. Polypectomy was done 5.6 (mean) times previously. After a 5-week, treatment-free, baseline period, patients were treated in a double-blind fashion with either budesonide or placebo during 4 weeks. After this treatment period, placebo-treated patients started receiving budesonide in an open trial for an additional 4 weeks. The patients rated their nasal symptoms daily. Nasal examinations and nasal inspiratory flow rate (IFR) measurements were done at clinic visits. After 3 and 4 weeks of treatment, the response to budesonide was significantly greater than response to placebo. The greater reduction in nasal blockage caused by polyps, observed on physical examination, p = 0.005, was mirrored by an increase in nasal IFR (p = 0.0001). Patient rating of the severity and frequency of nasal blockage were reduced more by budesonide than by placebo (p less than or equal to 0.0005). Switching placebo-treated patients to budesonide treatment resulted in a reduction of nasal blockage (p less than 0.001) and an increase in nasal IFR (p less than 0.001). The results demonstrate that topical nasal budesonide, 400 micrograms two times a day, is an effective treatment of nasal polyps. PMID- 2262650 TI - Selective desensitization to seminal plasma protein fractions after immunotherapy for postcoital anaphylaxis. AB - A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262651 TI - Diagnostic laboratory immunology/dual certification workshop report. PMID- 2262652 TI - Research workshop report. PMID- 2262653 TI - Recruitment workshop report. PMID- 2262654 TI - Patient-care workshop report. PMID- 2262655 TI - Women's health: is anatomy still destiny? PMID- 2262656 TI - Abuse in medical education. PMID- 2262657 TI - Toward improving women's health care. PMID- 2262658 TI - Women's health as a multidisciplinary specialty: an exploratory proposal. AB - The purpose of this paper is to encourage the development of women's health as a multidisciplinary specialty. The idea for such a specialty arose from the grass roots women's health movement of the 1960s, whose tenets were rapidly embraced by physicians sympathetic to its ideals, especially members of the American Medical Women's Association. Women's health would be a multidisciplinary specialty offering service to a specific patient population, analogous to geriatric medicine. It would blend primary care, ambulatory obstetrics-gynecology, and psychiatry with additional training in endocrinology, nutrition, sports medicine, and orthopaedics. Suggestions for residency training and specialty certification are included. PMID- 2262659 TI - Woman as other: the premise of medicine. PMID- 2262660 TI - Region IV: Women's Medical Society of Cleveland. PMID- 2262661 TI - Domestic violence: physicians a link to prevention. PMID- 2262662 TI - Vagal action on atrioventricular conduction and its inhibition by sympathetic stimulation and neuropeptide Y in anaesthetised dogs. AB - The observed change in atrioventricular conduction time (PR interval) in response to vagal stimulation is the result of two opposing effects; PR interval increases in response to the direct action of the vagus on atrioventricular nodal cells (direct effect), and the accompanying slowing of heart rate acts to decrease PR interval (indirect effect). The relationships between these opposing effects were studied in anaesthetised dogs. This study has shown that the increase in PR interval in response to vagal stimulation is well correlated with vagal stimulation frequency and can be regarded as linear. This is so for unpaced and paced hearts. We have also shown there is an increase in the sensitivity of the relationship between increase in PR interval and vagal stimulation frequency during pacing. This increase in sensitivity is attributable to the elimination of the indirect effect of the slowing of heart rate. During atrial pacing, the relationship between pulse interval and PR interval resembles a hyperbola. At low pulse intervals (i.e. fast heart rates) the PR interval increases. This is in agreement with previous qualitative findings and is related to the functional refractory period of the atrioventricular cells. The action of sympathetic stimulation and injection of neuropeptide Y has not been studied previously. The vagally induced increase in atrioventricular conduction time is attenuated for many minutes following stimulation of the cardiac sympathetic nerve at 16 Hz for 2 min or by intravenous injection of neuropeptide Y (25-50 micrograms/kg). Stimulation of the right cardiac sympathetic nerve evokes a significantly stronger inhibition of the vagally induced prolongation of pulse interval than stimulation of the left sympathetic nerve. On the other hand, stimulation of the left or right sympathetic nerves cause similar inhibition of vagal action on atrioventricular conduction time. PMID- 2262663 TI - Smooth muscle growth in the mature rat: role of sympathetic innervation. AB - The role of sympathetic innervation in maintaining smooth muscle structure and function was investigated in the mature rat. Superior tarsal muscle volume, smooth muscle cell nuclear size and packing density, and alpha-adrenoceptor mediated contractions were assessed in Sprague-Dawley rats at 3 months of age, and in rats at 6 months of age in which one muscle had intact sympathetic innervation and the contralateral mate was sympathectomized at 3 months. Body weight was stable between 3 and 6 months. In contrast, both maximum contraction and muscle volume increased by more than 50% in the innervated organ, while chronic sympathectomy prevented these increases. Both nuclear packing density and nuclear size increased with age. The greater packing density was abolished by sympathectomy, but nuclear enlargement was not. Adrenoceptor supersensitivity was not observed, although the agonist dose producing 50% maximum contraction varied as a function of contractile capacity. It is concluded that superior tarsal smooth muscle growth continues independently of changes in body weight in the mature rat. Structural and functional deficits observed following chronic sympathetic denervation of this muscle are attributable to prevention of growth rather than regressions in size and contractile capacity. PMID- 2262664 TI - Lesions of the anterior hypothalamic area increase arterial pressure in NaCl sensitive spontaneously hypertensive rats. AB - In NaCl-sensitive spontaneously hypertensive rats, diets high in NaCl increase arterial pressure and peripheral sympathetic nervous system activity and decrease the sympatho-inhibition mediated by the anterior hypothalamic area. To test the importance of the defect in anterior hypothalamic area-mediated sympatho inhibition in the pathogenesis of NaCl-sensitive hypertension, bilateral ibotenic acid lesions of the anterior hypothalamic area were made in NaCl-sensitive spontaneous hypertensive rats, in NaCl-resistant spontaneously hypertensive rats and in normotensive, NaCl-resistant Wistar Kyoto rats. In NaCl-sensitive spontaneous hypertensive rats on a basal NaCl diet, the anterior hypothalamic area lesions caused a rapid rise in arterial pressure within the first week after surgery; by 21 days after surgery, mean systolic arterial pressure of the lesion group was 24 mmHg higher than that of the sham-operated group. In a second experiment, NaCl-sensitive spontaneous hypertensive rats were placed on an 8% NaCl diet 1 day after the lesion of the anterior hypothalamic area. 5 days after the operation, the lesion group of NaCl-sensitive spontaneous hypertensive rats on the 8% NaCl diet had a significantly higher arterial pressure than the sham operated group, but by 1 week after the lesion, arterial pressures were not significantly different between the lesion and sham-operated NaCl-sensitive spontaneous hypertensive rats on the high NaCl diet. In Wistar Kyoto rats on a basal NaCl diet, lesions of the anterior hypothalamic area resulted in a small, transient elevation of arterial pressure, but no sustained effect. In NaCl resistant spontaneous hypertensive rats, the anterior hypothalamic area lesions did not affect arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262665 TI - Amino acid sensors sensitive to alanine and leucine exist in the hepato-portal system in the rat. AB - We reported the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the possible existence of other amino acid sensors such as L-alanine and L-leucine in the hepato-portal system in rats using an electrophysiological approach. Afferent discharges were recorded from fine filaments dissected from the peripheral cut end of the hepatic branch of the vagus nerve. Administration of 0.1, 1, and 10 mM L-alanine and L-leucine solution (0.1 ml) into the portal vein caused an increase in the discharge rate of hepatic vagal afferents in a dose-dependent manner. The results suggest the existence of vagal amino acid sensors which are sensitive to alanine and leucine in the hepato-portal system. PMID- 2262666 TI - Analysis of vascular responses evoked in the cutaneous circulation of one hand by cooling the contralateral hand. AB - In 11 healthy human subjects, cutaneous red cell flux in the thenar eminence of the left hand was measured by a Laser Doppler meter, while the right hand was transferred sequentially from water at 33 degrees C, to water at 16 degrees C for 5 min, to water at 33 degrees C (1st experimental run) and then to water at 16 degrees C for 2 min (2nd experimental run). Red cell flux decreased from 33 +/- 10 (mean +/- SEM) to 19 +/- 5* perfusion units (pu) by the end of the 2nd min of cooling (* P less than 0.05 paired t-test), but had returned to 27 +/- 8 pu by the 5th min. Arterial pressure, measured by sphygmomanometry from the left arm at the 5th min (1st run) and 2nd min (2nd run) did not change, indicating the changes in red cell flux reflected changes in cutaneous vascular resistance. By contrast, when these experiments were repeated with a cuff on the right arm inflated to 56-62 mmHg to impede venous outflow from the cooled limb, there were no changes in red cell flux in the contralateral hand, nor in arterial pressure. Occlusion per se had no effect on red cell flux. Thus, we propose that cooling one hand evokes a short-lasting reflex constriction in the cutaneous circulation of the contralateral hand which is mainly mediated by core thermoreceptors affected by a reduction in blood temperature, rather than by peripheral thermoreceptors in the cooled hand. The contrast between this proposal and views based on earlier studies is discussed. PMID- 2262667 TI - Brainstem evoked response to dorsal vagal gastric input from the proximal stomach. AB - Unitary responses to electrical stimulation of gastric vagal fibers, that serve the proximal stomach and join the dorsal vagal trunk, were bilaterally distributed in nucleus tractus solitarus (NTS) in the brainstem of the cat. The vagally activated brainstem responses consisted of single or multiple spikes with a mean latency of 281 (SD +/- 43 ms) which translated into a conduction velocity of less than 1 m/s. Ninety-eight percent of the responses were orthodromic in character. Twenty percent of the gastric vagally-evoked brainstem unitary responses received input from both the dorsal and ventral vagal trunks. Excitatory and inhibitory convergent interactions were observed in the brainstem units receiving gastric input from both the dorsal and ventral vagal trunks. PMID- 2262668 TI - Is the CCK-8 induced relaxation of the feline sphincter of Oddi mediated by VIP neurons? AB - The regional, intraarterial, injection of CCK-8 elicits reciprocal effects on the motility of the extrahepatic biliary tree in the cat: the contraction of the gallbladder and a relaxation of the sphincter of Oddi as well as of the duodenal wall. After neural blockade with tetrodotoxin the responses of the sphincter to CCK-8 were blocked, and the responses of the gallbladder were markedly reduced. After the regional administration of a VIP antiserum the sphincter relaxation in response to CCK-8 was blocked. Immunocytochemically it was demonstrated that the feline sphincter contains a rich VIP-ergic innervation, while CCK-like immunoreactivity was found only in mucosal endocrine cells. The results indicate that CCK-8 selectively activates inhibitory VIP neurons innervating the sphincter. After the administration of a nonpeptide CCK-receptor antagonist, the CCK-8 induced motor responses of both the sphincter and the gallbladder were markedly reduced. This indicates that blockade of CCK-8 receptors involves muscular as well as neural CCK-receptors. PMID- 2262670 TI - From the museum. PMID- 2262669 TI - Intracellular recordings from "recurrent neurons" in the rat superior cervical ganglion. AB - Intracellular recordings in the isolated superior cervical ganglion of the rat showed that electrical stimulation of the cervical sympathetic trunk elicited in a cluster of neurons localized in the caudal part of the ganglion synaptically driven action potentials, and propagated potentials having the features of typical antidromic spikes. The results demonstrate that these neurons, besides synapsing with common preganglionic fibres, project their axons to the cervical sympathetic trunk. The recurrent neurons showed a very low threshold to direct intracellular stimulation and a high input resistance, suggesting that they have a small size. Almost all recurrent neurons were activated synaptically also by stimulating the postganglionic trunks, indicating that they are innervated by collaterals of preganglionic through-fibres which are known to sustain a direct pathway between pre- and postganglionic nerves. Moreover, some recurrent neurons could also be activated antidromically following stimulation of the external carotid nerve, indicating that their axons divide into collaterals which project not only to the preganglionic trunk but also to a postganglionic nerve. The presence of recurrent neurons in the superior cervical ganglion of the rat provides further evidence for the concept that sympathetic ganglia consist of discrete cell subpopulations which are segregated in different regions and probably subserve different functions. PMID- 2262671 TI - Computerized visual fields. PMID- 2262672 TI - Intercostal pulmonary/diaphragmatic hernia. AB - A case of post-traumatic herniation of the lung and diaphragm through the lateral thoracic wall is presented. The pathogenesis of lung hernias, their clinical signs and symptoms, as well as methods of radiographic diagnosis, are discussed. PMID- 2262673 TI - Nonfunctioning paraganglioma of the liver, gallbladder and common bile duct. AB - Paragangliomas are rare extra-adrenal neoplasms of neural crest origin. Although most of these lesions are of retroperitoneal origin, paragangliomas have been reported at a host of remote sites, including the urinary bladder, larynx, orbit and lung. In our review of the literature, we discovered only solitary case reports of such neoplasms involving the gallbladder and hepatic duct. We report a case of paraganglioma simultaneously involving the liver, gallbladder and common bile duct, as well as celiac and portal lymph nodes. Our findings add paraganglioma to the list of differential diagnoses for hypervascular portacaval space lesions. Furthermore, the radiographic appearance of this unusual tumor may be sufficiently distinctive to suggest the correct histologic diagnosis preoperatively. PMID- 2262674 TI - Medical indications and contraindications for eye donation. AB - Potentially useful and valuable donor-eye tissue is lost because physicians decide erroneously that certain deceased people are not suitable donors. The Indiana Lions Eye Bank Inc. needs and will receive with gratitude any and all donated eyes. Donated ocular tissue can be used for research or teaching, if not for actual transplantation. All deceased people should be regarded as suitable eye donors, except when the cause of death or other factors might pose risks for enucleators themselves. PMID- 2262675 TI - Osteoarthritis of the carpometacarpal joint of the thumb. PMID- 2262676 TI - Indiana's living will after Cruzan. PMID- 2262677 TI - The dignity of death: some practical considerations for physicians. PMID- 2262678 TI - Beyond Cruzan: making life support decisions. PMID- 2262679 TI - Missed diagnosis results in tragedy. PMID- 2262680 TI - Port-wine stain: a new therapeutic approach to an old birth defect. PMID- 2262681 TI - Medical insurance is not the same as prepaid medicine. PMID- 2262682 TI - The winnowed wisdom of medicine. PMID- 2262683 TI - Leadership development for health for all. PMID- 2262685 TI - Peri-operative oxytetracycline in prophylaxis of surgical wound infections. AB - Experience with peri-operative oxytetracycline coverage in prevention of wound infection following elective surgery is presented; of 150 cases included in control group 21 developed infection (14%), whereas only 4 of the study group (170 cases) had infection (2.5%). The importance of peri-operative antibiotic umbrella is emphasised and some of the shortcomings of recommended schedule is highlighted. PMID- 2262684 TI - Incidence of hepatitis B surface antigen in liver diseases and voluntary blood donors. AB - A total of 5,606 samples were collected during January 1978 to December 1983. Out of which 4,900 were of voluntary blood donors, 564 of acute hepatitis, 130 of liver cirrhosis and 12 from hepatocellular carcinoma cases. All these samples were studied by counter immune-electro-osmophoresis (CIEP) for the presence of hepatitis B surface antigen (HBsAg). The HBsAg were detected in 40 samples from voluntary donors (0.8%), 122 cases of acute hepatitis (21.6%), 20 cases of liver cirrhosis (15.3%) and 2 cases of hepatocellular carcinoma (16.6%). PMID- 2262686 TI - Respiratory disorders in females of Delhi. AB - A retrospective study was carried out on 1532 female patients attending chest clinic, over a period of 13 years. The incidence of smoking was found to be 6.6%, maximum incidence (17%) being in those above 60 years of age. High incidence (66%) of exposure to kitchen smoke was observed in women above 40 years of age. Chronic bronchitis was found to be the commonest illness followed by bronchial asthma, pulmonary tuberculosis and bronchiectasis. Bronchial asthma and pulmonary tuberculosis were common in younger age groups, while above the age of 40 years 42% patients had chronic bronchitis and 27% had bronchiectasis. Incidence of smoking and exposure to kitchen smoke was also high in this subset. This shows that they may be important contributory factors for chronic obstructive pulmonary disease in females. Evidence of chronic cor pulmonale was found in 130 (8.5%) patients. Maximum incidence (28%) was seen in the age group of above 60 years. Chronic bronchitis with or without emphysema turned out to be the commonest cause of cor pulmonale, followed by bronchiectasis, pulmonary tuberculosis and bronchial asthma. PMID- 2262687 TI - Blood donation and risk of post-transfusion hepatitis. AB - A survey was conducted among 300 blood donors of urban and rural population (the Sunderbans) and paid donors to evaluate the nutritional status, serum proteins, immunoglobulin and alanine aminotransferase (ALT) on the persistence of carrier state for post-transfusion hepatitis (PTH). Paid donors showed lowering of serum albumin and elevation of immunoglobulin and ALT. Nutritional and immunoglobulin profiles of rural donors of the Sunderbans, differed from those of voluntary donors of urban area. In the presence of subclinical hepatitis, ALT measurement alone is not a reliable guide for identification of individual carriers. PMID- 2262688 TI - Does optic nerve injury require decompression? AB - Forty patients with indirect optic nerve injury were prospectively analysed. Ultimate outcome on conservative management were correlated to their visual evoked potential (VEP) finding and the need for optic nerve decompression was questioned. An associated indirect optic nerve injury was observed in 2% of all head injuries. Ethmoid fracture was recorded in 2 patients and optic canal fracture was recorded in one patient. CT scanning for optic canal and for the orbit revealed abnormality in none of these patients. All the patients were managed conservatively and received intravenous dexamethasone for 48 hours followed by oral prednisolone therapy. Optic nerve decompression was not undertaken. VEPs were present in 18 patients of whom 4 had normal VEPs. Twenty patients had visual improvement. Amongst the patients with positive VEPs 89% had visual improvement. It is concluded that VEP study may help in avoiding unnecessary decompression of the optic nerve. PMID- 2262689 TI - Osteopetrosis in an infant. PMID- 2262690 TI - Malignant melanoma of vulva. PMID- 2262691 TI - Diagnosis of olfactory neuroblastoma by cytology. PMID- 2262692 TI - Eaton-Lambert syndrome: an early and initial presentation in a case of bronchogenic carcinoma. PMID- 2262693 TI - A new approach to classification of angina pectoris with reference to its management. PMID- 2262694 TI - Placental transfer of paracetamol. PMID- 2262695 TI - Depression. PMID- 2262696 TI - Management of violent patients. PMID- 2262697 TI - Mobilising traditional birth attendants for the safe motherhood. PMID- 2262698 TI - Training for geriatric medicine in India: an urgent need for a nationwide training system. PMID- 2262699 TI - Sociobiologic factors influencing low birth weight at a rural project hospital. AB - The incidence of low birth weight (less than or equal to 2500 g) was 38.9% among 2292 singleton live births at a rural project hospital in Haryana. Only 7.0% of the newborns weighed 2000 g or less. Female babies had a higher incidence of low birth weight. Other factors considered were maternal age, parity and literacy and father's literacy. Young mothers (less than 20 years) had a higher incidence of low birth weight. Similarly parents who were illiterate or educated to below the primary grade also had a higher incidence of low birth weight. The maximum percentage of low birth weight was seen in the primiparous mothers. An increase of low birth weight was also seen after the 4th parity. The best outcome was at para 4. PMID- 2262700 TI - Evoked potentials in severe head injuries: a prospective study of 40 cases. AB - Evoked potential (EP) studies were performed in 40 severe head injury patients with Glasgow Coma Scale 8 or below. CT scans were performed in all to evaluate the intracranial pathology. EP studies were performed within 48 hours of admission and outcome was correlated to the initial EP findings. Normal brainstem auditory evoked potentials (BAEP) and sensory evoked potentials (SEP) were recorded in 23 and 17 cases with a good recovery in 86.9% and 82.3% respectively. Absent BAEP and SEP were recorded in 6 and 10 cases with a good recovery in 33% and 50% respectively. When both were normal good outcome was recorded in 92.8% cases. All the patients in whom both BAEP and SEP were absent had a poor outcome. In this study BAEP had a better predictive value than SEP. PMID- 2262701 TI - Effects of metoclopramide and ranitidine on gastric fluid volume and its acidity. AB - The effects of metoclopramide 10 mg and ranitidine 150 mg on gastric fluid volume and its pH are studied when given orally either alone or in combination, 3 hours before induction of anaesthesia in adult surgical patients. The study shows that metoclopramide causes reduction of gastric fluid volume but does not elevate its pH. Ranitidine elevates the pH of gastric fluid satisfactorily in all cases, but reduces the gastric volume below the critical level only in 50% cases. A combination of the said two drugs offered most satisfactory protection against acid aspiration syndrome almost in all cases. This regime seems to be superior to either ranitidine or metoclopramide alone in order to reduce the risk factors for aspiration of gastric contents. PMID- 2262702 TI - Glycosylated haemoglobin (HbA1c) levels in normal pregnancy: sequential changes and relation to birth weight. AB - Twenty-five healthy pregnant females with the absence of family history of diabetes mellitus were investigated serially for glycosylated haemoglobin (HbA1c) as per cent haemoglobin A1 at the interval of 4 weeks. HbA1c values were also determined in 10 healthy non-pregnant females who were studied as control cases. As compared to non-pregnant females HbA1c values were found to be low at 14-16 weeks of pregnancy (4.9 +/- 0.25%). After 16 weeks the HbA1c levels showed an upward trend to reach maximum at 32-34 weeks (5.54 +/- 0.19%). After 34 weeks the levels fell again to reach the lowest by 40 weeks of gestation (4.8 +/- 0.203%). Statistically highly significant relationship (p less than 0.001) was found between the HbA1c values and birth weight, lower values were associated with low birth weight and with increasing HbA1c values birth weight was found to be correspondingly increased. PMID- 2262703 TI - Neurological manifestations associated with bronchogenic carcinoma. AB - Neurological manifestations of bronchogenic carcinoma were studied in 50 cases, 42% of whom showed neurological abnormalities with 6% having more than one type. Recurrent laryngeal nerve paralysis (20%) was the commonest, phrenic nerve paralysis (2%), paraneoplastic syndrome (12%), Pancoast's syndrome (10%) and metastatic involvement of central nervous system (4%) were other neurological manifestations. No evidence of encephalitis, motor neurone disease, myelopathy, Eaton-Lambert syndrome, myositis and drug-induced peripheral neuropathy was found in this study. PMID- 2262704 TI - Five minutes' field study on each Indian hockey player in a coaching camp. AB - Peak expiratory flow rate (PEFR) was measured using portable Wright's peak flow meter on 21 male hockey players of Indian national hockey team probables attending a zonal coaching camp. The mean PEFR was observed to be 580.95 +/- 43.34 1/minute. The PEFR in hockey players were higher than those recorded in inter-university 'kabaddi', basketball players and football goalkeepers. All the group of players had shown higher mean PEFR than those of age matched healthy Indian males. PMID- 2262705 TI - Struma ovarii. PMID- 2262706 TI - Vasa praevia. PMID- 2262707 TI - ECG changes in a case of attempted hanging. PMID- 2262709 TI - Finance Bill, 1990: new income-tax amendments. PMID- 2262708 TI - Current thoughts of non-sporing anaerobes in health and disease. PMID- 2262710 TI - Snake bites in India and its management. PMID- 2262711 TI - Renal manifestations of leprosy. PMID- 2262712 TI - Inter-observer agreement and clinical diagnosis of leprosy for prophylaxis studies. AB - Clinical diagnosis is still the most useful tool for detecting early cases of leprosy in field research. In prophylaxis studies accuracy of clinical diagnosis of leprosy is important during intake as well as for measuring efficacy of the intervention. This paper reports our observations regarding the extent of inter observer variations in clinical diagnosis of leprosy and its implications for a prophylaxis study. Information on 225 suspects and cases of leprosy, each examined independently by three senior workers after initial standardization, was used for this purpose. Agreement among the examiners regarding the presence of skin patch, thickened nerve trunk and sensory deficit was fairly high (Kappa = 0.7). Agreement on the presence of infiltration in a skin patch was not satisfactory (Kappa = 0.4-0.5). It was observed that in clinical diagnosis of leprosy, presence of skin patch and sensory deficit, as well as thickened nerve trunk and related anaesthesia were correlated observations. The influence of inter-observer variations on defining leprosy problem in the community can be quite large. The paper suggests some ways of overcoming the problem. PMID- 2262713 TI - Sub-clinical infection with Mycobacterium leprae in household contacts of leprosy. AB - 870 household contacts of leprosy patients were examined for sub-clinical infection with M. leprae by smear (skin and nasal), lepromin and FLA-ABS tests. 0.6%, 3.3%, 71.5% and 14.4% of the contacts were found to be positive for skin smear, nasal smear, lepromin and FLA-ABS tests respectively. An analysis of the results revealed that 4% of the lepromin positive contacts and 3.6% of the lepromin negative contacts were positive to both FLA-ABS and skin or nasal smear. PMID- 2262714 TI - Pattern of drug compliance in leprosy patients attending urban centres--a longitudinal study. AB - The pattern of drug compliance in 485 leprosy patients attending urban leprosy centres in Bombay was studied for 2 years. The study subjects included 113 patients with paucibacillary leprosy under dapsone monotherapy, 241 patients with paucibacillary leprosy under multidrug therapy and 131 patients with multibacillary leprosy under multidrug therapy. Their urine samples had been checked at least 6 times during the 2 years by DDS tile test at the time of their clinic attendance. The urine test results were not disclosed to the patients, but patients showing negative results were counselled about the need for regular drug intake. 35% of the patients were "Regular through out", 13% were "Irregular through out" and the other 52% who "Tended to be irregular" in their drug intake became "Regular" after counselling. Regularity in drug compliance was better in patients on multidrug therapy than in those on monotherapy. It is suggested that periodic testing of urine for checking for regularity of drug intake and subsequent counselling of patients should be made a routine practice to maintain drug compliance at a high level. PMID- 2262715 TI - Assessment of testicular volume in bacilliferous leprosy: correlation with clinical parameters. AB - Testicular involvement in leprosy was studied in 30 multi-bacillary (BL/LL) patients. Ten (33.3%) gave past history of type II reactions, of whom nine (30%) gave history of testicular pain and/or swelling. Decreased libido was a common complaint (63.3%). Gynaecomastia was noted in 3 patients (10%) and altered hair pattern in 11 patients (36.7%). Testicular sensation was impaired in 10 (33.3%) patients. Testicular volume was assessed objectively using the Prader orchidometer and found to be reduced in nine (30%) patients. Reduction in testicular volume correlated with longer duration of disease and a past history of type II reaction. PMID- 2262716 TI - Thalidomide in type-2 lepra reaction--a clinical experience. AB - A clinical experience of using thalidomide in type-2 lepra reaction (ENL) in 90 male patients--57 with lepromatous leprosy (LL) and 33 with borderline lepromatous leprosy (BL)--is described. All the patients responded well although some took a longer time to improve. No major side effects were observed except for giddiness in 10 and gastrointestinal upsets in 7 patients. Thalidomide thus appears to be a very effective drug in the treatment of severe type-2 lepra reaction and apart from its historically well-documented embryopathic effects, does not seem to have any other serious side effects in the patients under study. PMID- 2262717 TI - Bone marrow cyto-morphological changes in multibacillary leprosy. AB - Seventy-two cases of multibacillary leprosy were investigated for cytomorphological changes and presence of lepra bacilli in bone marrow. These patients were divided in two groups. Group A (28) comprised of new cases and group B (44) of those receiving treatment. Myeloid hyperplasia was mostly seen in patients of group B who had erythema nodosum leprosum. Megaloblastic change in erythroblasts was seen frequently in both the groups. While average number of plasma cells and macrophages was on the higher side of normal range, detection of large number of plasma cells underlined enhanced humoral response and created diagnostic problem with multiple myeloma. Morphological changes in the macrophages, their collections and epithelioid cell granulomas were observed in bone marrow. Their nature and significance is discussed. PMID- 2262718 TI - Disability index of hands and feet in patients attending an urban leprosy clinic. AB - 189 leprosy patients including 20 from a leprosy colony having disabilities and deformities were graded by the WHO (1960) classification and their disability indices were calculated. Disabilities occurred more frequently in males and the disability index was significantly higher in those with longer duration of the disease and in multibacillary patients. Majority of the disabled patients (82.5%) were manual workers, but the highest disability index was observed in beggars. Irregularly treated and untreated patients had significantly higher disability indices (DI 2.40 and DI 1.40) than those taking regular treatment (DI 1.09). No correlation was found between severity of disability and occurrence of type I and type II reactions. Disabilities of hands and feet occurred with equal frequency. PMID- 2262719 TI - Some observations on skin smear examination. AB - 40 slit and scrape smears in a planned study and 35 routine smears picked up from the laboratory were examined. An end-to-end examination of the smears detected additional positives and gave a higher bacterial index than what was reported in the routine. Acid-fast bacilli were found to be distributed in only 1 to 3 per cent of the fields in the smears. The bacilli were found mostly in the centre and in narrow bands between centre and periphery of the smears. Some of the high BI smears were found to contain areas completely free from bacilli. PMID- 2262720 TI - Health education for the successful implementation of MDT. AB - The importance and goals of health education in leprosy are pointed out. The responsibilities of the health education are outlined. The role of health education in the context of the MDT programme is discussed. PMID- 2262721 TI - Is leprosy bacillus a chemo-autotrophic nocardioform organism? AB - Numerous attempts at in vitro cultivation of the leprosy bacillus have all proved to be unsuccessful. Recently, we have repeatedly isolated chemo-autotrophic nocardioform (CAN) organisms in pure culture from multibacillary cases of leprosy. We find that these resemble the leprosy bacillus in many respects and suggest that the leprosy bacillus may be closer to the genus Nocardia than to Mycobacterium, and that it may be a chemo-autotroph, requiring only simple sources of carbon and nitrogen for its growth. This is in contrast to most other human pathogens, which are heterotrophs requiring complex sources of carbon and nitrogen for their growth. This could offer a possible explanation for the repeated failure at in vitro cultivation of the leprosy bacillus. PMID- 2262722 TI - Serum mucoproteins and plasma fibrinogen levels in recurrent erythema nodosum leprosum (ENL) syndrome in lepromatous leprosy. PMID- 2262723 TI - Polyneuritic leprosy changing into borderline tuberculoid (BT). PMID- 2262724 TI - Absence of clinico pathological correlation in a case of BT leprosy. PMID- 2262725 TI - Leprosy and multicentric lupus vulgaris. PMID- 2262726 TI - Legal aspects of leprosy. PMID- 2262727 TI - Leprosy lesions at unusual sites. PMID- 2262728 TI - Rejoinder. PMID- 2262729 TI - [Study of bone metabolism for breast cancer by MD (microdensitometry) method]. AB - Bone is one of the involved organs of distant metastasis in breast cancer. We examined bone metabolism by microdensitometry (MD) method in 94 patients with breast cancer (40 with bone metastasis and 54 without it) and 10 with benign breast diseases. There was no significant difference among the three groups in the background factors of menopausal status and hormone receptors status. MCI, GSmin, sigma GS/D and bone pattern by MD method in breast cancer patients with bone metastasis were significantly lower than those in the other groups. There were slight reverse correlation between sigma GS/D and serum ALP. MCI and sigma GS/D indices corrected by ages were also significantly lower in bone metastasis (p less than 0.01). These indices in most of the patients with bone metastasis gradually decreased as the lesion progressed. The results revealed that microdensitometric analysis of bone metastasis for breast cancer was of use for the diagnosis and evaluation of therapeutic effect in the follow-up study. PMID- 2262730 TI - [Immunohistochemical study of fibronectin and laminin on gastric cancer]. AB - Frozen samples of normal gastric tissue (n = 80), gastric adenocarcinoma (n = 80), lymphnode metastases (n = 17) and liver metastases (n = 2) were investigated immunohistochemically for determination of fibronectin (FN) and laminin (LM). On monoclonal antibody, FN was seen in the gland basement membrane, scattered tissue and the vessel basement membrane in normal gastric tissue. On polyclonal antibody, FN was seen in the gland surface cells, the stomach gland cells and some portions of muscle fiber cells in normal gastric tissue, too. On both monoclonal and polyclonal antibody, LM was seen in the gland basement membrane, the vessel basement membrane, the vessel endothelial cells, and the fibroblast in normal gastric tissue. But on polyclonal antibody, LM staining in gland basement membrane was thicker than monoclonal antibody. These demonstrated that the monoclonal antibody was superior to the polyclonal antibody in specificity. In gastric adenocarcinoma, FN was not seen in the carcinoma gland basement membrane but in the tissue around the carcinoma. These suggested that FN had a share in the malignant transformation and the fibrous tissue formation. LM was seen in the carcinoma gland basement membrane in eighteen of thirty-six well-differentiated adenocarcinomas and two of fourteen moderately-differentiated adenocarcinomas. Well-differentiated adenocarcinoma were divided into two groups; a LM-positive group, and LM-negative group. These two groups were then compared for vein eroding, and lymph-node metastases, and the differences between the two groups found to be slight and not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262731 TI - [Non-Hodgkin's lymphoma of the Waldeyer's ring: the treatment results of the past 22 years and the significance of CHOP]. AB - From 1966 through 1988, 124 patients with non-Hodgkin's lymphoma of the Waldeyer's ring were treated. Seventy patients were male, and 54 were female. Age ranged from 5 to 81 years with a median value of 53 years. Pathological slides were reviewed and reclassified according to the Working Formulation. Diffuse large cell type was most common (53%). Since 1981, CHOP has been incorporated into the treatment including stage I and II patients. During these 22 years, new imaging modalities have developed, and an upstage rate by using those modalities has increased from 5% to 9%. In order to make the comparison meaningful, we used clinical stage determined at the day of the first visit. Fifty-one patients were clinical stage I, 64 were stage II, seven were stage III, and two were stage IV. B symptom was seen in 8 patients. Relapse developed in 45 patients (41%) out of 111 who achieved complete remission, and distant relapse was most frequent (89%). Salvage therapy was successful in only three patients of the 45 relapsed patients. Overall 5-year freedom from relapse (FFR) were 38% for the patients treated until 1980, and 69% for the patients treated thereafter (p less than 0.01). Addition of CHOP to radiotherapy has increased 5-year FFR of the stage II patients from 31% to 81% (p less than 0.01). In stage I, 5-year FFR was 71% in the patients treated with CHOP and radiotherapy, and it was 27% treated without CHOP. But the difference has no statistical significance, and we can not rule out the presence of selection bias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262732 TI - Effects of etoposide (VP-16) on the survival and progression of cultured HeLa S3 cells through the cell cycle. AB - The survival of cultured HeLa S3 cells and their progression through the cell cycle after exposure to Etoposide (VP-16) were studied. The dose survival curve of exponentially growing cells was of a biphasic nature; the curve had an exponential slope starting from a small shoulder, and finally attained a plateau against increasing concentrations of the drug. Throughout the cell cycle, VP-16 exerted its main killing activity on cells in the late S and G2 phases, whereas cells in the G1 phase were resistant to the drug. By using a low concentration of VP-16, which allowed 85% of the treated cells to survive, it was found that the inhibition of the cell progression by the drug was greatest in the late S and G2 phases. PMID- 2262733 TI - [Radiotherapy for endobronchially invading recurrence of esophageal cancer after resective surgery]. AB - Sixty-eight patients with endobronchially invading recurrence of esophageal cancer after resective surgery were treated with radiotherapy from 1966 to 1988. The mean interval between resective surgery and diagnosis of recurrence was 11.1 months, that was significantly shortened in a3 group. The dose of radiation for recurrence ranged from 2 to 70.3 Gy, with a mean dose of 42.6 Gy. The mean survival time after treatment of recurrence was 4.9 months. The dose of radiation was found to have a positive correlation with survival time. The cause of death was bleeding in 20 patients, and respiratory failure in 36. High dose of radiation was thought to induce high incidence of bleeding. The results indicated that external beam radiotherapy with conventional fractionation was not so much effective for the recurrence. PMID- 2262734 TI - [Treatment and prognosis of primary malignant melanoma of the oral cavity--an analysis of 12 cases and 96 reported cases]. AB - The treatment methods and prognosis were discussed in 12 patients of oral melanoma who were treated at Dept. of Oral and Maxillofacial Surgery, Kobe Univ. School of Medicine from 1975 to 1989, with a review of 96 cases published in the Japanese literature between 1984 and 1988, and the following findings were obtained. 1. Eleven our 12 cases were acral lentiginous melanoma (ALM), and one case was nodular melanoma (NM). 2. The early two cases were died of distant metastasis. Of the recent ten cases which were underwent surgical excision combined with adjuvant immunochemotherapy with DTIC, ACNU, VCR and OK-432, nine cases had good prognosis, and one case was died of local recurrence. 3. The prognosis of the reported cases was poor because of local recurrence and distant metastasis. PMID- 2262735 TI - [Ultrasound and CT evaluation of cervical lymph node metastasis of oral cancer]. AB - A comparison of the results of clinical diagnosis and ultrasound (US) and CT examinations was carried out in 43 patients who underwent radical neck dissection. We examined the site, size, depth and other features of lymph nodes which were unable to be detected by physical examination. US and CT proved superior to conventional clinical examination in detecting metastatic nodes. US and CT revealed that the disease in seven necks (12%) was not N1 but N2b, while in six of nine necks it changed from N0 to N positive. The features of metastatic lymph nodes on US and CT were clarified, and it was found that the detection of cervical metastatic nodes by a combination of US and CT is the most reliable method for assessing metastasis from tumors of the oral cavity. PMID- 2262736 TI - [Oral etoposide therapy in stage III-IV ovarian carcinoma]. AB - Seven patients with Stage III-IV ovarian carcinoma were treated with oral etoposide. The patients received a dose of 25 or 50 mg/day/body for every day or 21 consecutive days every one months. Four patients received this treatment as second line chemotherapy, two as initial chemotherapy and one as maintenance chemotherapy. One of 6 patients with measurable tumor had complete response, one had partial response and four had no changes. One patient with embryonal carcinoma, who received this treatment as maintenance chemotherapy is in no relapse for 2 years and 2 months. Leucopenia with a WBC under 3,000/mm3 was seen in 3 cases. Oral mucositis occurred in 2 cases, hair loss and gastrointestinal toxicities in 1 case. This method of oral administration is effective, tolerated and convenient for advanced ovarian carcinoma and recurrence following prior, vigorous chemotherapy in a outpatient clinic. PMID- 2262737 TI - [Effective continuous intraarterial chemotherapy for a patient with FIGO stage IIIb cervical adenocarcinoma invasing the bladder wall]. AB - A patient with FIGO stage IIIb adenocarcinoma of the uterine cervix (moderately differentiated, endocervical type) underwent an exploratory laparotomy because of a direct cancer invasion to the bladder wall, and then she was treated with consecutive intraarterial (IA) CDDP (10 mg/day) combined with continuous IA 5-FU (250 mg/day). Six weeks after, CR (complete response) was obtained by this IA chemotherapy (total dose; 5-FU: 10,500 mg, CDDP: 300 mg). Further 5-weeks-IA chemotherapy was added to keep the "CR" effect (final total dose; 5-FU: 19,250 mg, CDDP: 500 mg). The only toxic sign was a mild nausea. The patient's PS (performance status) was 0 (normal activity) and thereafter she could undergo a "curative" radical hysterectomy. The cancer invasion to the bladder wall observed at the first exploratory surgery completely disappeared histologically as well as macroscopically. In obtained material, small "viable" cancer focus was found in the cervical canal but the margin was free, and all nodes were negative. Postoperatively, the patient has receiving a continuous IA 5-FU (125 mg/day) for 13 months as a maintenance and she is free of disease (NED) with a normal activity (PS = 0). The present treatment modality is considered to be promising for advanced cervical adenocarcinoma having a poor prognosis due to its low sensitivity to radiotherapy. PMID- 2262738 TI - Radiology corner. Tunica albuginea cyst. PMID- 2262739 TI - The right to die: public perceptions and attitudes in metropolitan Baton Rouge. AB - The right to die movement is gaining momentum. Forty states, including Louisiana, have passed living will statues. Survey results indicate that relatively few people have accurate knowledge of the living will concept, and less than 4% have actually executed a living will. When informed of their rights, nearly two thirds of the sample would consider executing a living will or appointing a health care agent. Specific kinds of medical procedures desired in hypothetical terminal care situations vary considerably, and vary also according to certain socioeconomic characteristics. situations vary considerably, and vary also according to certain socioeconomic characteristics. PMID- 2262740 TI - Catamenial hemoptysis: a case report and review of the literature. AB - A young woman with catamenial hemoptysis and pleuritic chest pain is reported. She had two living children and had undergone three abortions and a tubal ligation followed by menorrhagia and dysmenorrhea. Fiberoptic bronchoscopy revealed no abnormalities, but computed tomograms of the chest revealed bilateral lung densities, which waxed and waned during the menstrual cycle. When characteristic clinical and CT findings are present, bronchoscopy is not necessary for the diagnosis of pulmonary endometriosis. PMID- 2262741 TI - ECG of the month. Atrial mischief. Multifocal atrial tachycardia. PMID- 2262742 TI - Atypical mycobacterial infections. AB - Atypical mycobacterial infections play an important role in human pathogenicity. Mycobacterium avium complex has been reported to occur in 17% to 50% of individuals infected with human immunodeficiency virus. In the southwestern United States, Mycobacterium kansasii is reported to be a predominate mycobacterial infection in middle-aged men. The epidemiology of the pathological species is discussed along with current recommendations for chemotherapeutic regimens. PMID- 2262743 TI - Reinke's edema. AB - Reinke's edema is a benign disorder of the larynx. This pathological condition involving a potential laryngeal space is most often seen in middle-aged smokers, and has a slight female predilection. The diagnosis, histopathology, and conservative as well as surgical treatment modalities are discussed. PMID- 2262744 TI - Ventilatory control, exercise tolerance and respiratory dysfunction in Thai COPD patients. AB - This study was designed to investigate a group of Thai COPD patients for their respiratory centre sensitivity while breathing room-air and during CO2 rebreathing, and tests to determine exercise tolerance and degrees of respiratory dysfunction. Results in 56 patients as compared with 45 age-matched healthy subjects disclosed comparable data between both subject groups, with the single exception that one-third (35.7%) of the patients experienced stronger ventilatory drive while breathing room-air and a lower musculo-ventilation transfer index during room-air breathing as well as CO2 rebreathing. According to the base-line dyspnoea index, the majority of Thai COPD patients in this study suffered from a very severe respiratory dysfunction, which correlated well with results of their basic physiologic tests. PMID- 2262745 TI - ERCP in diagnosis of adult choledochal cyst: report of five cases. AB - ERCP is the most reliable diagnostic technique, and should be used as the method of choice in the investigation of patients suspected of having choledochal cyst. This technique gives an accurate demonstration of both the biliary and pancreatic ducts. No complications occurred from the procedure. PMID- 2262746 TI - In vitro drug susceptibility of Mycobacterium other than tubercle bacilli. AB - MOTT were isolated from clinical specimens from the Division of Mycobacteriology, Department of Microbiology, Siriraj Hospital, Mahidol University, and also from natural sources, namely water and soil in the Bangkok area from January to December, 1987. The strains isolated were as follows: 30 M. fortuitum fortuitum, 5 M. fortuitum peregrinum 3 M. fortuitum 3 rd. biovariant complex, 3 M. chelonae chelonae, 7 M. chelonae abscessus. Of these, 5 strains were isolated from clinical specimens and the other 43 were from the environment. The pattern of drug susceptibility to antituberculous and antimicrobial agents revealed that they were resistant to antituberculous agents but susceptible to aminoglycosides (which contain a central ring of 2-deoxystreptamine) such as amikacin (83% of cultures), netilmicin (83%), gentamicin (77%) and kanamycin (75%). Some strains were sensitive to tetracyclines (35%), but all were resistant to penicillins and cephalosporins. PMID- 2262747 TI - Carcinoma of the nasopharynx in Chiang Mai University Hospital: a review of 205 cases. AB - Carcinoma of the nasopharynx is one of the common head and neck cancers in Southeast Asia. We had studied 205 cases of nasopharyngeal cancer who attended the ENT clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand from 1980-1984. The majority of the patients were found in stage IV. One hundred and five patients received a curative dose of radiation therapy. The observed actuarial 5 year survival was 34 per cent. There was a significant decrease in survival of patients with T4 disease. Differences in age, sex, histopathology and N-stage did not affect the survival. So far, the only specific treatment we can offer patients is radiation therapy, so an earlier diagnosis must be established in order to get better results of treatment. PMID- 2262748 TI - Angiolymphoid hyperplasia with eosinophilia. AB - A 51-year-old Thai man had had a 5 cm x 7 cm swelling of the right upper eyelid and forehead for 4 months. There was a deep trench-like skin ulcer at the upper tarsal border, exuding thick, very foul smelling pus. The mass did not respond to treatment with massive, multiple antibiotics, although the pus and foul smelling improved after treatment directed against anaerobic organisms. The correct diagnosis of angiolymphoid hyperplasia with eosinophilia was finally made after the fourth biopsy. The swelling disappeared after four weekly intralesional injections of triamcinolone. PMID- 2262749 TI - Opsoclonus in malaria: the first report in the literature. AB - The first report in the literature of opsoclonus in malaria was presented. A 24 year-old woman had a two week history of high fever and lassitude. Physical examination revealed no specific neurological sign on admission. Ring form and gametocytes of Plasmodium falciparum were found in blood smear. Combined treatment of quinine and tetracycline were prescribed. She developed classical abnormal eye movement of opsoclonus and hand tremor on the following day, which gradually subsided on the tenth hospital day. Computed brain tomography and cerebrospinal fluid study were normal. She was discharged home after 3 weeks of admission with some occasional minimal opsoclonus without hand tremor. PMID- 2262750 TI - Myelolipoma of the adrenal gland. AB - A case of adrenal myelolipoma in a 43-year-old woman was incidentally discovered during the investigation of chronic diarrhea due to Giardia lamblia. This tumor can be preoperatively diagnosed by its characteristic appearance on nephrotomogram, ultrasonography, and computerized tomography. PMID- 2262751 TI - Pap smear examinations of women at the out-patient department of Siriraj Hospital. AB - Pelvic examinations in 1,906 women at the Gynaecological Room, Out-Patient Department, Siriraj Hospital, in June 1990 were studied. The range of ages was between 14 and 85 years, the mean age being 34.5 +/- 11.5 years. Almost three quarters (74.7%) of the cases had undergone Pap smear examinations; of these, 36.5 per cent followed up on the results and 6.7 per cent were sent the results by postcard as requested by the patients. The percentage of the clinical diagnoses in women who underwent pelvic and Pap smear examinations (Pap smear data are within the parentheses) were: 36.6 (29.0) no abnormal findings, 14.9 (10.5) vulvovaginitis and leukorrhea, 10.1 (9.7) cervicitis and cervical erosion, 5.6 (1.9) bleeding per os, 3.4 (0.3) abortion, and 3.3 (1.3) adnexitis. The mean age of the women with various diseases were: 27 years in cases of abortion; 30-34 years in women with inflammation of the vulva, vagina, cervix and adnexa, including bleeding per os; 41-45 years in women with cervical polyps, suspected carcinoma, precancer and carcinoma of the cervix, combined with myoma uteri; 48 years in women with relaxation of the genital organ. Every woman who underwent pelvic examination should have a Pap smear and VCE technique performed for the early detection of cervical carcinoma. Health care workers should also ensure that every patient follows up on the results. PMID- 2262752 TI - Hormonal and growth status in long term survivors of acute lymphoblastic leukemia (ALL) in children. AB - Nineteen children and adolescents in long-term complete remission from acute lymphoblastic leukemia (ALL) were studied for hormonal and growth status after cessation of therapy. Cranial irradiation of 600-2,400 cGy was given for C.N.S. prophylaxis in 18 out of 19 patients, and additional irradiation of 2,000 cGy was given to both testes of a prepubertal boy because of testicular infiltration. The time ranges after cranial irradiation and cessation of therapy at the time of study were 61-137 months and 5-127 months respectively. Thyroid hormone, cortisol and peak cortisol response after ACTH stimulation were normal in every tested children. Basal serum gonadotropin and sex steroid values were appropriate in the majority of patients. A child who received testicular irradiation, had elevated levels of gonadotropins. Glucagon stimulation test (GST) and/or L-Dopa propranolol test (DP test) were used to study growth hormone (GH) response. None had peak GH value less than 7 ng/ml. Ten patients had peak GH values of over 15 ng/ml. Nine female patients had normal puberty and regular menstruation. Eight out of ten male children also had normal puberty. All except two male patients had normal linear growth within 2 standard deviations of the mean. The mean attained final height of 11 children was not significantly different when compared to the mean predicted heights obtained from Bayley-Pinneau and Tanner methods. Excessive weight gain during and after cessation of chemotherapy was observed in the majority of children. Continuing long-term review of these children is essential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262753 TI - Status asthmaticus: an analysis of 560 episodes and comparison between mechanical and non-mechanical ventilation groups. AB - An analysis and comparison of 286 adult patients involving 560 episodes of status asthmaticus admitted to the Medical Service of Chulalongkorn Hospital during the years 1984 through 1988 were examined. There were 58 patients who required mechanical ventilation 75 times compared with 228 patients with 485 episodes of attack who did not require the use of mechanical ventilation. The increased risk factors for status asthmaticus among those who required assisted ventilation were as follows: younger age at onset of asthma, younger age of severe attack, chronic asthma (especially unstable asthma), previous history of intubation and mechanical ventilation, shorter duration of severe attack and extremely severe attack in the sitting position before arriving at the emergency room, receiving beta 2 adrenergic inhaler, mistakenly taking beta blockers, high fever (over 38 degrees C) as a result of respiratory tract infection, increased initial pulse rate (over 125 beats/minute) and white blood cell count of over 16,000/mm3, and pneumothorax on admission. Simple asthma and history of taking franol or tedral in status asthmaticus indicated a low risk for mechanical ventilation. The taking of glucocorticoids did not pose a risk to status asthmaticus requiring mechanical ventilation. PMID- 2262754 TI - A prospective study of ERCP in the investigation of the patients after acute non alcoholic pancreatitis. AB - ERCP was shown to be a safe diagnostic procedure within one week of resolution from acute pancreatitis in 46 patients. The bile duct was cannulated successfully in 95.7 per cent and the pancreatic duct in 89.1 per cent. The most common etiological factors in non-alcoholic acute pancreatitis were gall stone diseases (52.2%). ERCP was accurate in demonstrating the biliary causes of acute pancreatitis, and should be considered as a routine investigation for all suspected patients. PMID- 2262755 TI - Identification of urinary metabolites and quantitative measurement of creatinine by a proton nuclear magnetic resonance spectrometry. AB - 1H-NMR spectra of 60 human urine specimens were recorded without pretreatment by a JEOL FX 90 Q spectrometer operating at 89.55 MHz. The signals of the methyl protons of creatinine (3.04 +/- 0.02 ppm) were observed in all spot fasting morning urine samples collected from 7 healthy persons, 10 patients with nephrotic syndrome and 43 patients with diabetes mellitus. The concentrations of creatinine measured by NMR spectroscopy (Y) and the chemical assay based on the Jaffe reaction (X), over the range of 19-190 mg/dl, were compared by the least squares linear regression analysis (Y = 6.7799 + 0.6717 X). The mean urinary creatinine concentration by NMR spectroscopy appeared to be lower than that obtained by the Jaffe reaction at the normal and high normal levels. In the urine of 20 diabetic patients with an average blood glucose of 251.30 +/- 50.26 (SD) mg/dl typical spectra of the multiple large signals of glucose protons at position from 3.13 +/- 0.04 to 4.04 +/- 0.12 (SD) ppm were shown. Moreover, some urinary metabolites and amino acids spectra were occasionally detected at one time. PMID- 2262756 TI - Pituitary adenomas: immunohistochemical: study of 90 cases. AB - Pituitary tumors from 90 patients were investigated using immunohistochemical study and the results were correlated with clinical records. There were 32 benign prolactinomas and two malignant counterparts, 13 growth hormone positive tumors. 10 corticotropic adenomas, and 10 gonadotropic tumors. Four tumors showed positivity for both prolactin and growth hormone, one prolactin and gonadotropin. An example of mixed, luteinizing hormone, prolactin and growth hormone was observed. Additionally, there was an adenoma composed of two compartments secreting prolactin and growth hormone. One patient had a recurrent gonadotropin adenoma after surgical removal of the original prolactinoma. Fifteen tumors were negative for all hormones and most were nonfunctioning clinically. The clinicopathologic correlations were found to be good for prolactinoma, growth hormone positive tumors and for tumors producing both prolactin and growth hormones causing a combined feature of hyperprolactinemia and acromegaly. PMID- 2262757 TI - Socio-economic status and prevalence of intestinal parasitic infection in Thai adults residing in and around Bangkok metropolis. AB - Socio-economic factors relating to prevalence of intestinal helminthic infections were studied in 189 Thai adults residing in and around Bangkok. Questionaires were used to interview each individual about occupation, income, family occupation, family income and educational level. All participants were subjected to three microscopic stool examinations and to stool cultures for Stronglyoides stercoralis. Of 189, 34 were students (20%), 60 were unemployed (35%), and the remainder were employed in private or public sectors. The overall average personal incomes were low (less than US$ 1,000/year), while 56 per cent of them came from middle class families (US$ 2,000-4,000/year). Regarding the educational level, only 151 persons answered this question. Fourteen (9.3%) did not complete primary school; 20 (13.2%) completed primary school; 97 (64.2%) completed secondary or vocational school and 20 (13.2%) were university graduates. Prevalence of intestinal parasitic infection was 25 per cent (47/189) and 23.4 per cent (11/47) of infected individuals had multiple infections. The distribution among them was as follows: strongyloidiasis 30.5 per cent, hookworm 25.5 per cent, giardiasis 23.4 per cent, opistorchiasis 17 per cent, amoebiasis 12.8 per cent, trichuriasis 4.3 per cent, taeniasis 2 per cent and ascariasis 2 per cent. There were no statistical differences in incomes, occupations, family incomes and educational levels between infected and uninfected individuals. PMID- 2262758 TI - Spontaneous bacterial peritonitis in acute hepatitis B. AB - Spontaneous bacterial peritonitis is a disorder that occurs almost exclusively in patients with cirrhosis. Herein, we report a 22-year-old man with acute viral hepatitis B associated with spontaneous bacterial peritonitis which is a rare complication. The diagnosis was made at laparotomy, performed presumably to treat a perforated viscus, which resulted in a fatal outcome. PMID- 2262759 TI - Neurogenic pulmonary edema associated with meningitis. AB - A 17-year-old man presented with acute febrile, obtundation, nuchal rigidity and CSF pleocytosis with polymorphonuclear cell predominate. He developed acute pulmonary edema which could not be explained by other mechanisms. Meningitis appears to be another cause of neurogenic pulmonary edema. PMID- 2262760 TI - Younger and older adolescents' thinking about commitments. AB - One hundred and sixty-three adolescents listed factors they consider or would consider when choosing a career and a romantic partner, and defined "commitment" in an open-ended essay. Male and female ninth graders, twelfth graders, and college juniors, from public and private schools served as subjects. Gender, grade, and type of school differences were found in the types and number of different types of factors listed for the above commitments, but not in the number of factors listed. Conceptions of the nature of commitment became more complex with grade, and differed as a function of gender and of type of school. Females listed more "internal" factors than did males for romantic commitments. Males described commitment more contractually, women more affectively. Older students focused more upon long-term and internal concerns, and defined "commitment" more in terms of cognitive processing and emotional attachment than younger students. Implications for related areas of work are discussed. PMID- 2262761 TI - Patterns of affectivity in the transition to adolescence. AB - The present paper reports the findings of a factor analytic investigation of adolescent affect in a cross-sectional sample of 483 male and female fifth through ninth graders. Following the ESM method, adolescents carried electronic pagers and self-report booklets for one week. Students were paged seven times daily and completed self-report forms after each signal describing their moods and feelings. Principal components analysis yielded two internally consistent factors which were virtually identical to the positive and negative affect dimensions described in the literature on adult emotion. Contrary to findings reported in the developmental literature, arousal did not emerge as a dimension of adolescent affect. Further, the bipolar structure obtained for the entire sample, positive and negative affect, consistently emerged in separate analyses of adolescent gender and school groups. MANOVA analysis of estimated positive and negative affect scores indicated that while the underlying dimensions of adolescent affect were comparable to those observed for adults, variation along those dimensions may have been related to the social transitions (e.g., schooling) which punctuate adolescence. PMID- 2262762 TI - Relational aspects of identity: late adolescents' perceptions of their relationships with parents. AB - This study examines the relationship between late adolescents' identity status and their memories of their relationships to their parents. One hundred male and female undergraduates completed two questionnaires. The first assessed subjects' retrospective perceptions of their affective relationships with parents across five age periods: 1 to 5 years, 5 to 10 years, 10 to 15 years, 15 to 20 years, and the present. The second questionnaire, the Extended Objective Measure of Ego Identity Status, assessed subjects' current identity status. Trend analyses revealed: (1) a significant quadratic trend in identity committed subjects' ratings of the amount of love they felt for mother across the five age periods, and (2) a significant linear trend of increasing love from mother. In contrast, uncommitted subjects showed significant linear trends of decreasing love both for and from their mothers. Results are interpreted as evidence of the importance of resolution of identity issues to the establishment of feelings of intimacy between late adolescents and their parents. PMID- 2262763 TI - Relativism and stations of epistemic doubt. AB - This sequence of studies examined the role that relativistic thinking plays in the cognitive and social-emotional lives of adolescents. Study 1 introduces an assessment strategy and associated descriptive model employed in evaluating how 70 concrete and formal operational adolescents differently interpret and resolve problems involving competing knowledge claims. A second study explored the relations between the epistemic orientations evidenced by 61 of these subjects and their current level of identity development. Study 3 compared the epistemic assumptions of a group of 29 psychiatrically hospitalized adolescents with those of a matched group of normal controls. Results from these studies indicate that relativistic approaches to problems of belief entitlement are: a) routinely characteristic of most normal adolescents; b) available to formal operational, but not concrete operational individuals; c) associated with more mature ego identity statuses; and d) typically absent in groups of psychiatrically hospitalized youth. PMID- 2262764 TI - Spatial updating and training effects in the first year of human infancy. AB - The ability of infants to locate an invisible target after reorientation in their direction of facing was examined in a series of experiments. In a featureless environment, localization of the target site improved between 4 and 8 months. At 8 months it was shown to be dependent on the training procedure. Infants received either instrumental training in which they were trained to anticipate the occurrence of an event at the site, or association training in which one event immediately followed another regardless of their responses. After instrumental training, localization was dependent on visual cues whereas after association training it occurred whether or not visual cues were provided. Contrary to earlier findings, it was concluded that an updating strategy based on proprioceptive information is operative from the second half of the first year. PMID- 2262765 TI - Use of deoxyribonucleic acid (DNA) fingerprints for identity determination: comparison with traditional paternity testing methods--Part I. AB - A study involving comparison of the deoxyribonucleic acid (DNA) finger-printing test with traditional methods used for paternity testing is presented. Samples from 191 cases were tested for a series of blood group and polymorphic protein markers. DNA "fingerprints" were then obtained for all samples using the multilocus probes 33.6 and 33.15. The results of DNA fingerprinting correlated well with those of traditional methods and proved to be informative in cases where traditional methods yielded inconclusive or insufficient results. PMID- 2262766 TI - Trajectory reconstructions. I: Trace evidence in flight. AB - This paper reviews the use of trace evidence recovered from spent bullets in helping to establish trajectories. The use of information derived from such trace evidence combined with that from geometrical techniques of trajectory reconstruction and other data is discussed. Five cases are reviewed in which the analysis of trace evidential materials adhering to bullets was used to help reconstruct the event. PMID- 2262767 TI - High-performance liquid chromatography with column switching for the determination of cocaine and benzoylecgonine concentrations in vitreous humor. AB - A sample concentration technique was adapted for the determination of cocaine and benzoylecgonine (BE) concentrations in vitreous humor. Vitreous humor (0.5 mL) was diluted 1:1 with water and applied through a filter onto a 3-cm preconcentration column. Following a simple wash step, the analytes were flushed directly onto a reversed-phase analytical high-performance liquid chromatography (HPLC) system. Absolute recoveries were high (above 90%) and the chromatograms were free from interference. Analysis for the drug and its breakdown product was performed using ultraviolet (UV) visible photodiode array detection, which allowed confirmation of peak identity. Recognizable UV spectra could be measured with as little as 20 ng on column. Comparison of the drug levels in 27 blood and vitreous humor samples showed that, while there was only a low correlation between the blood and vitreous concentrations (R = 0.70), vitreous cocaine and BE determinations were good indicators of antemortem cocaine use. In almost all cases, the vitreous BE concentrations were higher than the cocaine concentrations. The technique was easy to perform and the vitreous samples were especially compatible with this low-labor analytical procedure. PMID- 2262768 TI - Further evaluation of probabilities in human scalp hair comparisons. AB - Placing value on associative hair evidence is an integral part of court presentation. A modified repeat of the hair probability study by Gaudette and Keeping has been undertaken, with steps taken to remedy shortcomings of the original work. The results of this study demonstrate that, with the application of rigid selection criteria, the frequency of coincidental matches in forensic science hair comparisons is low. It also demonstrates that routine hair classification is not feasible, because of inconsistency in examiner discrimination. The macroscopic selection of 5 to 13 mutually dissimilar hairs has been shown to be frequently unrepresentative of the microscopic range of features present in a known hair sample. PMID- 2262769 TI - Fluorometric determination of pseudocholinesterase activity in postmortem blood samples. AB - A fluorometric assay using 3-(p-hydroxyphenyl) propionic acid (HPPA) was conducted to determine the activity of pseudocholinesterase (ChE) [Enzyme Commission (EC) No. 3.1.1.8] in postmortem blood samples so as to test for organophosphate poisoning. By the enzymatic reaction of ChE, its substrate, benzoylcholine, produces choline, which is oxidized by choline oxidase to generate hydrogen peroxide. HPPA is oxidized by hydrogen peroxide and peroxidase to become the fluorogenic dimer whose concentration is measured fluorometrically at an excitation emission wavelength of 320 nm and an elimination emission wavelength of 404 nm. The selectivity and sensitivity of the present method were found to be superior to those of conventional pH and spectrophotometric methods. PMID- 2262770 TI - Effect of fabric washing on the presumptive identification of bloodstains. AB - The purpose of this study was to investigate the retention of blood stains on twelve different types of fabrics after washing at various drying times. The findings of this study, supported by chi-square analysis, indicate that the retention of bloodstains on washed fabrics depends upon the particular fiber composition of the fabric, the specific blood screening test used, and whether or not a detergent was used in the wash. The results of this research did not reveal a significant effect of the drying time on the retention of bloodstains, as tested during the 48-h limit of this experiment. The author concludes that the forensic serologist should consider the factors investigated in this study before rendering an opinion on the retention of bloodstains on washed garments. PMID- 2262771 TI - An application of probability theory to a group of breath-alcohol and blood alcohol data. AB - Many jurisdictions have "per se" driving-while-intoxicated (DWI) status expressed in terms of a blood-alcohol concentration (BAC) standard (in grams per 100 mL or the equivalent). Since breath-alcohol (BrAC) analysis is typically employed to determine BAC, there is often challenge to the use of an assumed 2100:1 conversion ratio. This concern may be relevant in light of considerable data that show a low percentage of cases in which BrAC greater than BAC, and this concern increases when the BrAC is used to predict BAC in the context of "per se" legislation. Probability theory provides a basis for estimating the likelihood of an individual having a BrAC greater than or equal to g/210 L with a corresponding BAC less than 0.10 g/100 mL. Actual field data from the state of Wisconsin (n = 404) were evaluated to determine the probability of this occurrence. The probability for this occurrence involves the multiplication law for independent events. The computed probability from the data was 0.018. The actual number of occurrences where BrAC greater than or equal to 0.10 g/210 L and BAC less than 0.10 g/100 mL was 5, resulting in a probability of 0.012. The concern of having BrAC greater than BAC at the critical "per se" level has a very low probability of occurrence, which thus supports the reasonableness of "per se" DWI legislation based upon a blood-alcohol standard determined by breath-alcohol analysis. PMID- 2262772 TI - Differences between multisite postmortem ethanol concentrations as related to agonal events. AB - In a study of postmortem ethanol concentrations, blood was withdrawn from the right atrium, ascending aorta, and inferior vena cava. These samples, vitreous humor, and gastric fluid were analyzed in 307 autopsies, where a minimum blood ethanol concentration of 0.05% weight/volume (w/v) was present. Premortem, agonal, and postmortem events were reviewed in an attempt to account for differences in blood ethanol concentrations between sites. The agonal aspiration of vomitus having at least 0.80% w/v ethanol appears to be associated with an increase in aortic ethanol concentrations. We conclude that valid interpretation of postmortem ethanol concentrations must take into consideration the possible entry of ethanol into the pulmonary venous circulation via the respiratory system. PMID- 2262773 TI - The usefulness of lung surfactant phospholipids (LSPs) in the diagnosis of drowning. AB - The authors have studied the usefulness of some lung surfactant phospholipids (LSPs) isolated from lung tissues as markers of drowning. Two different groups of rabbits were sacrificed by drowning in fresh and salt water, and their phospholipid compositions were compared with those of a non-drowned control series. For the phospholipids studied in lung lavages (phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl glycerol) the proportions differed between the control group and the drowned group, and between the fresh-water and salt-water drowned animals. According to these results, the lipids we have analyzed can be employed as markers in forensic autopsies, where it is necessary to differentiate between death by drowning and postmortem immersion and between fresh-water and salt-water drowning. In lung tissue, only phosphatidyl choline and phosphatidyl inositol showed significative differences. These results also confirm that LSPs are strongly affected in drowning. PMID- 2262774 TI - The accuracy of sex identification in European skeletal remains using the phenice characters. AB - Three documented European skeletal series were examined to assess the accuracy and reliability of the pubic variables described by Phenice for correctly identifying the sex of adult human skeletal remains. The accuracy and objectivity of these variables, as reported by Phenice, Kelley, Sutherland and Suchey, and Lovell, could not be confirmed on this European material. In general, the subpubic concavity feature, when used alone, proved to be the most reliable variable for sex identification. In this study, the level of correct sex identification that could be achieved using the Phenice variables was shown to be significantly affected by the previous experience of the observer. PMID- 2262775 TI - Euthanasia: a challenge for the forensic toxicologist. AB - People die daily in the hospital. Mostly, they die because their illnesses were no longer treatable (natural death). Unfortunately, some people die an unnatural death, in particular, as the result of euthanasia. In contrast to the situation in most countries, in the Netherlands euthanasia is accepted by the courts under strict conditions. It can be very difficult for the legal authorities to establish whether a person has died from natural causes or from suicide, euthanasia, or murder. In addition to the pathologist and the lawyer, the toxicologist also has a number of problems in showing whether euthanasia has been carried out. These can consist of the following analytical problems: (a) interactions--the patients involved have frequently been receiving a large number of toxic and nontoxic drugs simultaneously; (b) identification--not all drugs administered are included in general screening procedures; (c) metabolites--a large number of metabolites may have accumulated toward the end of a long therapeutic regimen; and (d) determination--determination of quaternary muscle relaxants and their various metabolites, as well as other drugs, can be problematic. There are also toxicokinetic problems; because of poor kidney and liver function, low serum albumen, general malaise, and interactions between these factors and other drugs, the kinetics of a given drug can differ from normal. This makes it all the more difficult to determine whether the patient died from an accumulation of medication or from a so-called "euthanetic" drug mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262776 TI - Capillary gas-liquid chromatography separation of phenethylamines in amphetamine positive urine samples. AB - Good gas chromatography (GC) separation of molecules is essential for clean gas chromatography/mass spectrometry (GC/MS) confirmation of compounds. The trifluoro derivatives of ephedrine (E) and methamphetamine (MA) coelute on dimethyl silicone capillary columns, such as DB-1, which are most commonly used by chromatographers. Methods are described to separate E and MA to aid GC/MS confirmations of methamphetamine, ephedrine, or both E and MA together, whichever may be present in Enzyme Immunoassay (EIA)-analyzed amphetamine-positive urine samples. The use of the heptafluoro derivatives of E and MA on a DB-1 column, or the trifluoro derivatives of E and MA on a DB-17 column, is suggested for good gas chromatographic separation. PMID- 2262777 TI - The detection of group specific component (Gc) in the general population of West Virginia. AB - An isoelectric focusing method is described for the detection of group specific component (Gc) in forensic casework. Gc can be subtyped in one day using this reliable and reproducible method. The gene frequency data collected indicate that the occurrence of Gc phenotypes in the population of West Virginia is consistent with established frequencies for the system. PMID- 2262778 TI - Fetal death due to nonlethal maternal carbon monoxide poisoning. AB - Fetal death due to acute carbon monoxide poisoning is rarely reported in the medical literature. Of the eight cases found in literature review, only one documented the fetal carboxyhemoglobin concentration. This paper reports a fetal death due to accidental nonlethal maternal carbon monoxide intoxication in which both maternal and fetal carboxyhemoglobin concentrations were obtained. The corrected carboxyhemoglobin concentration was 61% at the time of death in utero, while the maternal carboxyhemoglobin was measured at 7% after one hour of supplemental oxygen. The authors review the mechanisms of fetal death and emphasize the different carbon monoxide kinetics in the fetal circulation. PMID- 2262779 TI - A death resulting from trichlorotrifluoroethane poisoning. AB - Fatalities due to accidental exposure to chlorinated hydrocarbon in an industrial setting have been infrequently reported. The deaths in these cases have occurred within poorly ventilated, enclosed compartments or areas. A case is presented of a 16-year-old male who died as a result of exposure to trichlorotrifluoroethane while working in an open pit. Chromatographic results and tissue concentrations are presented. PMID- 2262780 TI - The tubular "cookie cutter" bullet: a unique projectile. AB - Recently marketed PMC (Pan Metal Corporation) Ultramag tubular hollow point ammunition is uniquely constructed with a two-part projectile composed of a tubular copper bullet and a Teflon wad. A fatal gunshot wound with this ammunition is described. A unique radiographic pattern and the results of test firing are also presented. PMID- 2262781 TI - Attempted murder with pancuronium. AB - A nurse was accused of attempting to murder her anesthesiologist husband on two occasions by administering to him a neuromuscular blocking agent. In both episodes, urine specimens were obtained from the victim shortly after the suspected assaults. The samples were initially tested fluorometrically using Rose Bengal dye as a pairing agent. Both were presumptively positive for pancuronium. Confirmation of these results was achieved by pairing the drug with potassium iodide, extracting the complex, and submitting the extract to thin-layer chromatography (TLC) cleanup, elution at the appropriate retardation factor (Rf), and, finally, gas chromatography/mass spectrometry (GC/MS) analysis in the selected-ion monitoring mode. The two quaternary amines of pancuronium appear to undergo pyrolytic N-demethylation in the injection port to yield an entity amenable to capillary column gas chromatography. The mass spectrum of the compound consists of a base peak of m/z 322, with additional fragments of 292, 323, 338, and 397 m/z, each of which was monitored. The confirmed positive findings were instrumental in adjudicating the case. PMID- 2262782 TI - The use of human skin in the fabrication of a bite mark template: two case reports. AB - Comparison of a suspected biter's dental arches with the patterned injury of a bite mark is especially difficult when the bite occurs in an anatomic location with a small radius of curvature or with complex or compound curves. The authors present two case reports in which human skin was used as a template for the reproduction of a bite. In one case the victim's skin was used; in the other, the skin of a anatomically similar person was used. The use of inked dental casts, photography, and transparent overlays significantly reduced the errors common to analysis of bite marks in these highly curved areas. PMID- 2262783 TI - Capillary column pyrolysis-gas chromatography of hair: a short study in personal identification. AB - Human head hairs from 18 individuals were analysed by capillary column pyrolysis gas chromatography (PyGC). The pyrograms showed several components, three of which were found to differ significantly among individuals. These major components were identified as benzene, toluene and styrene by gas chromatography mass spectrometry. As the result of capillary column PyGC of 18 amino acids, it was found that differences among the individuals were due to the different amounts of particular amino acids in the hair. The quantities of the components were, further, found not to change in 18 months. PMID- 2262784 TI - Toxicology and fly larvae on a putrefied cadaver. AB - Toxicological analyses on a putrefied cadaver are sometimes difficult to achieve, due to the absence of blood and/or urine. In this study, morphine and phenobarbital were simultaneously identified and assayed in several tissues of a putrefied cadaver and in the fly larvae of Calliphoridae found on the corpse. PMID- 2262785 TI - Biosynthesis of oleandomycin by Streptomyces antibioticus: influence of nutritional conditions and development of resistance. AB - The influence of different nutritional compounds on oleandomycin biosynthesis by Streptomyces antibioticus was studied, resulting in the design of a chemically defined medium for production of the antibiotic. Of the variety of carbon and nitrogen compounds tested, fructose and aspartic acid (carbon and nitrogen sources, respectively) supported the highest oleandomycin titres. Addition of propionate but not acetate, both precursors of the skeleton of the macrolide lactone ring, stimulated the biosynthesis of the antibiotic. Oleandomycin biosynthesis was repressed by glucose but not by phosphate. S. antibioticus develops oleandomycin resistance shortly before the antibiotic begins to be synthesized, showing a triphasic pattern of resistance: spores and producing mycelium are resistant, while non-producing mycelium is sensitive. PMID- 2262786 TI - Effects of cell wall deficiency on the synthesis of polysaccharide-degrading exoenzymes: a study on mycelial and wall-less phenotypes of the fz; sg; os-1 ('slime') triple mutant of Neurospora crassa. AB - The production of exoenzymes which degrade cellulose, polygalacturonic acid and xylan was studied in mycelial and wall-less phenotypic derivatives of Neurospora crassa obtained by vegetative selection applied to a single fz;sg;os-1 ('slime' like) segregant (strain RCP-3) of a cross 'slime' x wild type. The unrelated stable 'slime' strain FGSC 1118 was also studied. The synthesis of polysaccharide degrading enzymes was normally induced by polysaccharidic substrates and was sensitive to carbon-catabolite repression for both mycelium-forming phenotypes (mycelial intermediate and spheroplast-hyphal intermediate) of strain RCP-3. The stable 'slime' from RCP-3 produced cellulose-degrading activity and xylan degrading activity constitutively but was fully sensitive to glucose repression. The stable 'slime' RCP-3 did not synthesize polygalacturonic-acid-degrading activity, even in the presence of inducers. For the stable 'slime' FGSC 1118, all of the polysaccharide-degrading activities were produced constitutively and were markedly resistant to glucose repression. The possible epigenetic origin of the different properties of stable 'slimes' RCP-3 and FGSC 1118 is considered. These results may relate to the role of the cell surface in the processing of regulatory signals which control the adaptation of the fungal cell to the nutritional environment. PMID- 2262787 TI - Temperature adaptation in yeasts: the role of fatty acids. AB - Studies on the yeasts Candida oleophila, Candida utilis, Lipomyces starkeyi, Rhodosporidium toruloides and Saccharomyces cerevisiae revealed the existence of three different temperature adaptation responses involving changes in fatty acid composition. These conclusions were drawn by determining the growth rates, total cellular fatty acid content, fatty acid composition, degree of unsaturation, and the mean chain length of fatty acids over a range of growth temperatures. Within temperatures permitting growth, there were no changes in the major fatty acids of any of the yeasts, but the absolute amounts and relative compositions of the fatty acids did alter. In S. cerevisiae there were temperature-induced changes in the mean fatty acid chain length, whereas in R. toruloides there were changes in the degree of unsaturation. C. oleophila, C. utilis and L. starkeyi showed both responses, depending on whether the growth temperature was above or below 20-26 degrees C. Below 20-26 degrees C temperature-dependent changes were observed in the mean chain length whereas above 20-26 degrees C there were changes in the degree of unsaturation. PMID- 2262788 TI - Uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans. AB - The uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans was measured using a novel technique in which the cells were rapidly separated from their suspending medium by centrifugation through a layer of an inert oil. The uptake of [14C]cytosine was linear for 30 s for all concentrations of pyrimidine tested. In C. glabrata but not C. albicans cytosine transport was mediated by both a high affinity (Km 0.8 +/- 0.1 microM), low capacity [V 40 +/- 4 pmol (microliters cell water)-1 s-1] and a low affinity [Km 240 +/- 35 microM], high capacity system [V 770 +/- 170 pmol (microliters cell water)-1 s-1]. The cytosine permease in C. glabrata was specific for cytosine and 5-fluorocytosine. In C. albicans there was only one cytosine transport system [Km 2.4 +/- 0.3 microM; V 50 +/- 4 pmol (microliters cell water)-1 s-1]; this system also transported adenine, guanine and hypoxanthine. Differences in nucleoside transport were also observed for C. glabrata and C. albicans, with the uridine permease in C. glabrata transporting only uridine and 5-fluorouridine whereas cytidine and adenosine were also transported by the uridine permease in C. albicans. Studies on the effect of nucleoside analogues on uridine transport in C. glabrata demonstrated the importance of the sugar moiety in determining the specificity of transport, with a hydroxyl residue on C-2 being apparently essential for transport. PMID- 2262789 TI - The Streptomyces coelicolor A3(2) bldB region contains at least two genes involved in morphological development. AB - Streptomyces coelicolor A3(2) bldB mutants are blocked in the formation of aerial hyphae. A phage library of wild-type S. coelicolor DNA was used to isolate recombinant phages which restore wild-type morphological development to several bldB mutants. Of several mutations, one, bld-28, previously mapped at bldB was not complemented by the cloned region, indicating that the bldB locus is composed of at least two distinct genes. Partial localization of bldB-complementing activity showed that a 1.5 kb fragment is sufficient for complementation of the bld-15 mutation whereas bld-17 requires the same region as well as additional sequences. Under stringent conditions, genomic DNA hybridizing to the cloned sequences was absent from other Streptomyces species, including the closely related Streptomyces lividans 66. DNA sequences causing marked plasmid structural instability in S. coelicolor, but not in S. lividans, are also located in this region. PMID- 2262790 TI - Cloning, sequencing and analysis of expression of a Butyrivibrio fibrisolvens gene encoding a beta-glucosidase. AB - The cloning, expression and nucleotide sequence of a 3.74 kb DNA segment on pLS215 containing a beta-glucosidase gene (bglA) from Butyrivibrio fibrisolvens H17c was investigated. The B. fibrisolvens bglA open reading frame (ORF) of 2490 bp encoded a beta-glucosidase of 830 amino acid residues with a calculated Mr of 91,800. In Escherichia coli C600(pLS215) cells the beta-glucosidase was localized in the cytoplasm and these cells produced an additional protein with an apparent Mr of approximately 94,000. The bglA gene was expressed from its own regulatory region in E. coli and a single mRNA initiation point was identified upstream of the bglA ORF and adjacent to a promoter consensus sequence. The primary structure of the beta-glucosidase showed greater than 40% similarity with a domain of 237 amino acids present in the beta-glucosidases of Kluyveromyces fragilis and Clostridium thermocellum. The B. fibrisolvens beta-glucosidase hydrolysed cellobiose to a limited extent, cellotriose to cellobiose and glucose, and cellotetraose and cellopentaose to predominantly glucose. PMID- 2262791 TI - A cytoplasmically inherited mutation in the fungus Phycomyces blakesleeanus. AB - Fourteen mutants of the fungus Phycomyces blakesleeanus, showing high levels of resistance to copper, were isolated. In all the mutants, copper resistance behaved as a very variable and unstable trait. In the mutant strain MU102, the mutation was demonstrated to be cytoplasmically inherited. In addition, this mutant strain differed from the wild-type in growth, respiration rate, and shape and viability of spores. PMID- 2262792 TI - Construction of hybrid xylE genes between the two duplicate homologous genes from TOL plasmid pWW53: comparison of the kinetic properties of the gene products. AB - The two xylE genes for catechol 2,3-oxygenase, encoded by TOL plasmid pWW53, carry a common SalI restriction site within the reading frame. Each gene was cut at the SalI site and the 5' end of each gene spliced to the 3' end of the other to form hybrid genes, from both of which catalytically active catechol 2,3 oxygenase activities were expressed. The kinetic parameters were determined for the gene products of both the hybrid and the wild-type xylE genes with catechol, 3-methylcatechol and 4-methylcatechol as substrates. Comparison of the results suggested firstly, that the C-terminal regions of the enzymes determined both the binding and the catalytic specificity, and, secondly, that the N-terminal region of one of the enzymic gene products contained a secondary binding site which caused inhibition by excess substrate for methylcatechol substrates but not for catechol. One of the wild-type enzymes appeared to have an intrinsically higher activity for all three substrates than the other. This higher activity depended on the presence of both its C- and N-terminal regions, and in both hybrid enzymes, which contained only one of these regions, activity was significantly reduced. PMID- 2262793 TI - Extraction of membrane antigens from Brucella ovis and an assessment of their serological activity by immunoblotting. AB - The efficacy and selectivity of chaotropic and phase-partitioning procedures for the extraction of membrane proteins from Brucella ovis were compared with a standard Sarkosyl method. Major group 1, 2 and 3 outer-membrane proteins (OMPs) of B. ovis stained by Coomassie blue in SDS-PAGE gels had, respectively, apparent molecular masses of 81/82 kDa, 39-41 kDa and 30-32 kDa. The presence of these bands in the Sarkosyl extract of total membrane vesicles (TMVs) indicate that the procedure failed to selectively solubilize only inner-membrane proteins (IMPs). SDS-PAGE analyses also revealed the presence of OMPs and other additional bands following extraction of B. ovis TMVs by butanol phase-partitioning or with extraction solutions based on the chaotropic reagents potassium thiocyanate (KSCN), sodium salicylate (SSC) and lithium acetate (LAE). OMPs are therefore not selectively extracted by any one of these procedures. Based on the number and staining intensity of extracted membrane-associated polypeptides, the efficacy of different extraction procedures could be graded in decreasing order as follows: KSCN, SSC, butanol and LAE. Both butanol and SSC were particularly effective in extracting group 3 OMPs. Sera from chronic excretor rams were used to identify zones of seroreactivity in immunoblots. Essentially, two reactivity patterns were seen: strong antibody binding against polypeptides in zones A (46-85 kDa), C (28 32 kDa) and D (18-22 kDa) in one, and additional reactivity against zones B (34 44 kDa) and E (13-18 kDa) polypeptides in the other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262794 TI - Extensive heterogeneity of the protein composition of Chlamydia trachomatis following serial passage in two different cell lines. AB - To determine if the host-modulated adherence characteristics of the intracellular bacterial pathogen Chlamydia trachomatis were due to the acquisition of altered surface-exposed proteins, highly purified chlamydiae grown in two different host cells were analysed. Two serovars, L1 and E, were grown for multiple passages in both HeLa and McCoy host cells. Numerous protein differences in the chlamydial elementary bodies (EB) of each serovar grown in the two different hosts were detected by two-dimensional (2-D) gel electrophoresis and fluorography of radioactively labelled proteins. At least four to six serial passages in the alternative host were necessary before the changes were apparent. Iodination of suspensions of purified chlamydiae and 2-D electrophoresis revealed several surface proteins that were determined by the host cells in which the bacteria had replicated. These iodinated chlamydial proteins were removed by treatment of the iodinated EB with trypsin, indicating their location at the bacterial surface. Two of the major constituents of the outer-membrane complex, the cysteine- and methionine-rich 60 kDa and 40 kDa proteins, remained unchanged in both molecular mass and charge during the host adaptation. Several chlamydial proteins capable of binding iodinated host membrane preparations also exhibited host-dependent alterations. Immunoblotting experiments with a rabbit and a human polyclonal sera indicated that distinct host-specified chlamydial proteins were reactive with the two sera. PMID- 2262795 TI - Characterization of an rRNA gene-specific cDNA probe: applications in bacterial identification. AB - Discontinuous DNA complementary to Escherichia coli 16S + 23S ribosomal RNA was synthesized by random oligonucleotide priming using reverse transcriptase. cDNA generated from native or denatured rRNA template was labelled by incorporation of either [alpha-32P]dCTP or digoxigenin-labelled dUTP during synthesis, followed by template hydrolysis. The specific activity of the radiolabelled cDNA was 10(7) 10(8) c.p.m. (micrograms rRNA template)-1 with 60-92% incorporation after 5 h. The length of the reverse transcript was between 20 and 1140 nucleotides and was unaffected by exclusion of primer. The cDNA probe could detect 3 pg rRNA by quantitative slot blot. In the non-radiolabelling digoxigenin system 3 micrograms template gave 0.5-2.0 micrograms cDNA after 24 h with a length of between 100 and 1225 bases. This probe could detect 50 pg rRNA. Probes were evaluated in the comparison of Pasteurella haemolytica biotypes by hybridization to Southern blots of restriction-endonuclease-digested total DNA. The digoxigenin-labelled probe was used to identify clinical isolates of Campylobacter jejuni to demonstrate its potential use in laboratories requiring high-sensitivity detection without the use of radioisotopes. PMID- 2262796 TI - In memoriam Lucien J. Rubinstein, M.D. (1924-1990). PMID- 2262797 TI - The VM model of glioma: preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy. AB - A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro therapeutic model of human glioma. In this study we describe the preparation of MTS from this cell line. The in vitro chemosensitivity of 497-P(1) MTS has been examined and compared to the sensitivity of the monolayer culture. BCNU and CCNU both produced growth delay in MTS at doses below the ID50 of the monolayer culture. MTS, however, were considerably more resistant to vincristine and procarbazine when compared to the monolayer culture. PMID- 2262798 TI - Aldehyde dehydrogenase activity in xenografted human brain tumor in nude mice. Preliminary results in human glioma biopsies. AB - ALDH activity measured fluorimetrically using a high concentration of aliphatic aldehyde as substrate was studied in human glioblastomas grafted in nude mice. Compared with normal brain, ALDH activity is significantly increased in malignant glioma tissue, especially in the cytosolic subcellular fraction. Correlatively, in comparison with normal brain tissue, MDA levels were significantly reduced in whole homogenates and in cytosolic fractions of xenografted glioblastoma tissue. Preliminary results concerning human malignant glioma biopsies are in good agreement with our experimental data. In view of previous works, these results suggest a relationship between alterations in ALDH iso-enzymes activities and cytosolic aldehyde concentrations with respect to normal or tumoral cell growth. PMID- 2262799 TI - Spinal cord ganglioglioma presenting as hydrocephalus. AB - We report a case of a 5 year old boy with a spinal cord ganglioglioma and hydrocephalus. The insidious onset with back stiffness and hamstring tightness, the diagnosis by magnetic resonance imaging, and the treatment by total excision is described. An adequate proven explanation for the hydrocephalus is lacking. Mechanisms which have been proposed include impaired cerebrospinal fluid absorption from increased cerebrospinal fluid protein, and arachnoiditis. PMID- 2262800 TI - Modification of the 8 drugs in 1 day regimen: feasibility of substitution of other agents. AB - Six children (ages 2 to 14 years) with recurrent or poor risk primary brain tumors were treated with the '8 drugs in 1 day' chemotherapy regimen. As renal function deteriorated (median after five cycles), carboplatin was substituted in place of cisplatin at a median dose of 300 mg/m2 as a one hour infusion at hour three. Four patients also had their lomustine deleted and replaced by etoposide 100 mg/m2 at hour four. Compared to earlier cycles of chemotherapy, there was a moderate increase in transfusion requirement (especially platelets) but the incidences of fever and neutropenia were unchanged. Glomerular function as measured by nuclear glomerular filtration rate (GFR) remained unchanged or improved at the end of therapy. The severity of nausea and vomiting after substitution was markedly improved. Four of the six patients are still in complete remission 19 to 41 months after diagnosis or recurrence. It is feasible to substitute carboplatin and etoposide into the '8 drugs in 1 day' regimen when extramedullary toxicity is found. PMID- 2262801 TI - Primitive pineal tumor with retinoblastomatous and retinal/ciliary epithelial differentiation: an immunohistochemical study. AB - A one year old boy was found to have a large tumor encompassing the pineal region and extending towards the third and lateral ventricles and quadrigeminal plate. The tumor was composed mostly of small, undifferentiated cells. Some small cells were arranged in Flexner-Wintersteiner rosettes and a few displayed fleurettes. The tumor contained immature cartilage and skeletal muscle and numerous clusters of pigmented epithelial-like cells which, histologically, resembled those found in melanotic neuroectodermal tumors of infancy (retinal anlage tumors) and retinal or ciliary epithelium. Immunologic stains demonstrated neurofilaments synaptophysin and retinal S-antigen in some of the small cells and transthyretin in some of the epithelial-like cells. The findings indicate that certain primary pineal parenchymal tumors have features in common with tumors of the ocular medullary epithelium. PMID- 2262802 TI - A case of large cell CNS lymphoma associated with a systemic small cell lymphocytic lymphoma. AB - A case is reported of a 59 y/o woman with a large cell CNS lymphoma and a small cell lymphocytic lymphoma in the bone marrow. The brain tumor underwent spontaneous regression and subsequent regrowth while there was slow progression of the systemic small cell lymphoma. The CNS lymphoma regressed rapidly following treatment with prednisone and cyclophosphamide. We hypothesize that the small cell lymphoma in this patient may represent an underlying immunodeficiency disorder. PMID- 2262803 TI - Primary central nervous system lymphoma imitates multiple sclerosis. AB - Primary central nervous system lymphoma (PCNSL) can be confused with multiple sclerosis (MS) in patients who present with neurological dysfunction, a non enhancing periventricular lesion, and CSF pleocytosis. Administration of corticosteroid causes clinical improvement and regression of PCNSL in some patients which may be interpreted as a steroid-induced remission from an exacerbation of MS. Sustained clinical dependence upon corticosteroid is unusual in MS, and should lead to consideration of PCNSL. Repeat CSF examination and gadolinium-enhanced MRI scan obtained off corticosteroid should differentiate between the two diagnostic possibilities. PMID- 2262804 TI - Cerebral vasculopathy and infarction in a woman with carcinomatous meningitis. PMID- 2262805 TI - A cerebral glioma model for experimental therapy and in vivo invasion studies in syngeneic BD IX rats. AB - An in vivo glioma model was developed in syngeneic BD IX rats. The BT4An tumor was derived from serial in vivo passages of the BT4A tumor, originally induced from transformed fetal rat brain cells after transplacental exposure to ethylnitrosourea. The cell line was characterized for the presence of neuroglial differentiation markers, chromosome content and cell cycle distribution as determined by flowcytometry. A standardized method for i.c. tumor induction was developed, and the tumors were investigated by light and electron microscopy and for evidence of blood-brain barrier disruption. Tumor cell ability for phagocytosis was studied, as this property may be important for the invasion pattern of the tumors. We conclude that the model seems suitable for both in vivo therapy and invasion studies. The tumor had 100% tumor take, yielded a predictable symptom-free life span after inoculation, had a characteristic histological picture of an aggressive glioma, and the blood-brain barrier within the tumor was in part disrupted. Compared to the parent cell line, there was loss of neuroglial differentiation markers, the chromosomal distribution was changed, and the ability for phagocytosis was practically lost. PMID- 2262806 TI - Failure of tryptophan deficiency to reduce specifically serum levels of transthyretin or albumin in rats. AB - Because transthyretin (TTR) is a tryptophan-rich molecule and a sensitive nutritional marker, tryptophan deficiency might markedly influence the circulating level of TTR. The effect of severe tryptophan (Trp) deficiency on serum TTR, as well as on albumin and transferrin levels, was studied in growing rats for 8 d. The animals were then refed a control diet for 12 d. The Trp deficient and control diets contained 0.008 and 0.34% Trp, respectively. A loss of body weight and a dramatic reduction in food intake were observed in the Trp deficient rats. Although serum total Trp concentration was significantly less in these rats than in pair-fed controls, serum TTR declined to the same extent in both groups compared to control rats fed ad libitum. Albumin concentrations were not altered, but transferrin levels declined slightly in the Trp-deficient rats compared to both the pair-fed group and the controls fed ad libitum. Refeeding the control diet to Trp-deficient rats restored total and free Trp concentrations, as well as TTR and transferrin levels, but body weight and food intake remained lower than in the control group. To examine the effect of moderate Trp restriction, rats were fed for 2 wk a diet whose Trp content was 50% less than that of the control diet. Although total and free Trp concentrations were significantly lower in the rats fed the Trp-deficient diet than in the control group, body weight, food intake and TTR levels were similar in both groups. The results suggest that acute and severe Trp deficiency per se does not modify TTR and albumin levels. PMID- 2262807 TI - Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance. AB - The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade. PMID- 2262808 TI - Cholesterol metabolism in mature and immature rats fed animal and plant protein. AB - In two feeding experiments immature (180 g) and mature rats (370 g) were fed a semi-purified diet containing 20% of a protein source (casein, wheat gluten, soybean or potato protein) for 4 wk. Food supply was restricted to 15 g daily. As compared to casein, plant proteins induced significantly lower concentrations of plasma total cholesterol and high density lipoprotein (HDL) cholesterol. The plasma cholesterol increase associated with aging was not prevented by consumption of casein, soybean or potato protein, but wheat gluten seemed to be effective. Lecithin-cholesterol acyltransferase (LCAT) activity was not significantly different in rats of the same age fed different plant proteins, whereas the esterification rate was lower in rats fed casein. With aging the LCAT activity generally decreased. As compared to the casein groups, the rats fed plant proteins showed higher excretion of fecal neutral and acidic steroids. Among the groups fed plant proteins, the fecal output of steroids was variable. Significantly negative correlations were found between fecal total sterol excretion and plasma total cholesterol or HDL cholesterol, respectively. Plant proteins showed a faster migration rate in the stomach, whereas their migration and absorption were slower in the first half of the small intestine. A relation between nonabsorbed nitrogen-containing substances and sterol excretion was hypothesized. PMID- 2262809 TI - Tissue distribution and prediction of total body folate of rats. AB - To clarify relationships between dietary folic acid intake, blood levels and body stores of folate, rats were fed an amino acid-based diet supplemented with 0, 0.125, 0.5, 1, 2 or 4 mg folic acid/kg diet for 25 d. Folate concentrations of carcass, liver, gastrointestinal (GI) tract, kidney, spleen, testes, heart and lung from rats fed the folate-free diet were 0.06 +/- 0.01, 0.73 +/- 0.08, 0.05 +/- 0.01, 0.39 +/- 0.01, 0.05 +/- 0.01, 0.17 +/- 0.01, 0.02 +/- 0.01 and 0.02 +/- 0.01 micrograms/g, respectively. Serum and erythrocyte concentrations and total body stores were 0.88 +/- 0.16 ng/mL, 0.30 +/- 0.01 micrograms/mL and 13.9 +/- 0.7 micrograms, respectively. Body folate distribution was carcass, 55.6 +/- 1.4%; liver, 26.0 +/- 1.9%; erythrocytes, 7.7 +/- 0.4%; kidney, 4.8 +/- 0.2%; GI tract, 3.0 +/- 0.2%; and testes, 2.5 +/- 0.2%. Carcass content dropped to 38% whereas liver content increased to 44% in rats fed the highest dietary level. Tissue concentrations were correlated with one another and with dietary folate levels. Under these experimental conditions total body folate could be predicted from serum folate, but the general applicability of this relationship requires further study. PMID- 2262810 TI - Bioavailability of folates in selected foods incorporated into amino acid-based diets fed to rats. AB - Two experiments were conducted to determine the feasibility of using a folate depletion/repletion protocol with rats fed an amino acid-based diet to measure the bioavailability of food folate. Growth, liver folate and serum folate of depleted rats that were fed test foods incorporated into a folate-free, amino acid-based diet were standardized against similar responses of rats fed known amounts of folic acid incorporated into the same diet. Bioavailability of folate of cooked broccoli, refried beans and orange juice concentrate in experiment 1 was 80-89, 113 and 62%, respectively, based on growth response; in experiment 2, values for cooked and raw broccoli, cooked cabbage and cantaloupe were 95, 103, 74 and 81%, respectively. The results demonstrate that in addition to serum and liver folate concentrations, growth may be a useful response criterion to evaluate the bioavailability of folates in foods. Further research is needed to determine the relevance of these bioavailability estimates to human nutrition. PMID- 2262811 TI - Structural and geometrical isomers of carotenoids in human plasma. AB - We have quantitatively analyzed human plasma for the following carotenoids: all trans-lutein, all-trans-zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, the sum of all-trans-lycopene and its cis isomers, alpha-carotene and beta-carotene. In addition, we have tentatively identified and quantified 13-cis-lutein and 13 cis-zeaxanthin in human plasma. The latter two cis isomers are also apparent in samples of two common food items, spinach and corn meal. We have analyzed the ratios of all of the members of the beta, beta family of carotenoids (zeaxanthin, beta-cryptoxanthin and beta-carotene) to their corresponding beta, epsilon structural isomers (lutein, alpha-cryptoxanthin and alpha-carotene) in human plasma. There are marked differences in these ratios, with beta-carotene and beta cryptoxanthin predominating in the carotene and monohydroxy-xanthophyll classes and lutein predominating in the dihydroxy-xanthophyll class. These differences could be attributable to dietary intake or to specific mechanisms in the way humans absorb and utilize these compounds. PMID- 2262812 TI - Plasma carotenoids of monkeys (Macaca fascicularis and Saimiri sciureus) fed a nonpurified diet. AB - The major carotenoid pigments in the plasma and in a common, nonpurified diet of two species of monkeys (Macaca fascicularis and Saimiri sciureus) were measured. The xanthophylls, lutein, zeaxanthin, alpha-cryptoxanthin, and beta cryptoxanthin, were the principal carotenoids in both the diet and the plasma. Lutein and zeaxanthin were abundant in the all-trans, the 9-cis, and the 13-cis geometrical isomers in the diet, but the 9-cis form was rarely measurable in plasma. However, the 13-cis isomers of lutein and zeaxanthin were found in higher proportions in plasma than in the diet. For both the monohydroxy-xanthophylls, alpha-cryptoxanthin and beta-cryptoxanthin, and the dihydroxy-xanthophylls, lutein and zeaxanthin, the beta, beta structural isomer (beta-cryptoxanthin or zeaxanthin) is less abundant than the beta, epsilon isomer in plasma than in the diet. These results indicate substantial specificity in the absorption or retention of closely related carotenoid isomers in primates. The proportions of different geometrical isomers of lutein and zeaxanthin in the plasma of both species of monkeys were nearly identical and were similar to human values. The hydrocarbon carotenoids, alpha-carotene, beta-carotene and lycopene were usually undetectable in monkey plasma. The monkeys appear to be like humans in their utilization of lutein and zeaxanthin but distinctly different in some other aspects of carotenoid utilization. PMID- 2262813 TI - Unequal distribution of a stable isotopic calcium tracer between casein and whey fractions of infant formulas, human milk and cow's milk. AB - Measurement of calcium absorption with tracers assumes a complete equilibration of tracer with milk calcium. In this study, the equilibration of tracer between the micellar casein and soluble fractions (primarily whey) of infant formulas, human milk and cow's milk was measured in vitro using milk samples enriched with 42Ca and analyzed by thermal ionization mass spectrometry. Incomplete equilibration of tracer occurred with the micellar casein fraction of all milks. The least equilibration with micellar casein was found with premature infant formula, for which the ratio of slopes of the equilibration lines (whey/casein) was 8.5/1. These differences may be due to Ca-casein binding in cow's milk-based formulas. The effects of the lack of tracer equilibration in vivo cannot be determined. However, unequal bioavailability of casein- vs. whey-bound Ca may exist. PMID- 2262814 TI - Dietary crude protein levels and the effect of isoproterenol on in vitro lipogenesis in the chicken. AB - Experiments were conducted with male broiler breeder chickens to determine the metabolic effects of two levels of dietary crude protein fed during a protein reversal regimen on subsequent responses to a beta-adrenergic agonist (isoproterenol) in vitro. Day-old chickens were fed diets containing either 12 or 20% crude protein until 14 d of age and then switched to the opposite diet until 28 d. In experiment 1, chickens were killed at 28 d, and in experiment 2, at intervals following the switch at 14 d. In vitro lipogenesis and lipolysis were determined. The hepatic enzymes isocitrate dehydrogenase, malic enzyme and fatty acid synthetase were determined during the 14 to 28 d of age growth period. Both in vitro lipogenesis and lipolysis were greater at 28 d when chickens were fed the 12% rather than the 20% protein diet. Neither 0 to 14 d of age dietary treatment influenced 28-d metabolic parameters. In contrast, the 12% protein diet during the first 14-d period depressed body weight (160 g vs. 320 g; p less than 0.05) and weight gain during the 14 to 28 d of age period regardless of dietary crude protein levels (508 g vs. 626 g; p less than 0.05). Lipogenesis and lipolysis were at their highest points 4 d following the dietary switch. Isoproterenol decreased in vitro lipogenesis 70% in all dietary treatment groups. Stimulated lipolysis was not affected by nutritional status and was twice the unstimulated rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262815 TI - Glutathione augments in vitro proliferative responses of lymphocytes to concanavalin A to a greater degree in old than in young rats. AB - The proliferative response of splenocytes to concanavalin A (Con A) is significantly lower in aged than in young rats. The addition of reduced (GSH) but not oxidized (GSSG) gamma-glutamylcysteinyl-glycine (glutathione) in vitro totally reverses the defective proliferative response of splenocytes from aged rats. The inhibitor of gamma-glutamylcysteine synthetase, buthionine sulfoximine, abrogates the in vitro proliferation of splenocytes from young rats activated with Con A, and this effect is significantly reversed by addition of GSH. The enhancing effects of GSH on proliferation of Con A-activated splenocytes of both young and old rats are apparent as early as 24 h and are still evident as late as 72 h in culture. Both cysteine and 2-mercaptoethanol are able to mimic the effect of GSH in causing a greater increase in Con A-induced proliferative responses of splenocytes from old rats (eightfold) as compared to young animals (threefold). Although 2-mercaptoethanol increases expression of membrane-bound transferrin receptors on both Con A-activated splenocytes and T lymphocytes, this alone does not account for the greater enhancement of Con A-induced proliferation of splenocytes from old as compared to young rats. These data are consistent with the hypothesis that the glutathione peroxidase-dependent detoxification system is defective in T lymphocytes of aged rats. PMID- 2262816 TI - Roles of dietary corn oil in the regulation of cytochromes P450 and glutathione S transferases in rat liver. AB - To study the molecular mechanisms by which dietary lipids affect the levels of cytochrome P450 (P450) isozymes, male Sprague-Dawley rats were fed either fat free (FF) or 20% corn oil (CO) diet in combination with one of the following three treatments: no inducer, phenobarbital (PB) and acetone. Dietary CO did not affect the constitutive level of P450IIB (PB-inducible), but it affected the induction of P450IIB by PB treatment. The induction of P450IIB by PB in the CO group as determined by 7-pentoxy-resorufin O-dealkylase activity and immunochemically detected protein level was twofold higher than that in the FF group, and this difference was also reflected in the level of mRNA for this enzyme. In contrast, dietary CO increased the constitutive level of P450IIE (ethanol-inducible) twofold as indicated by N-nitrosodimethylamine demethylase activity and immunochemically detectable protein, but it had no effect on the induction of P450IIE by acetone. The induced level of P450IIE by acetone in the CO group did not differ from that in the FF group as measured by the enzyme activity and protein level. It was demonstrated that dietary CO affects P450IIB and IIE activities by altering the concentration of the isozymes rather than by modulating their catalytic activities. In addition, dietary CO increased the microsomal testosterone 6 beta-hydroxylase activity but not 7 alpha- and 2 alpha hydroxylase activities, suggesting an increase in P450IIIA and/or IIC13 but not in IIA1 and IIC11, respectively. Dietary CO also affected the constitutive and induced levels of glutathione S-transferase (GST) isozymes in a different manner: it increased the constitutive level of GST-B but not that of GST-A. Nevertheless, it was important for the induction of both GST-A and GST-B by PB treatment. The results suggest that lipid nutrition affects xenobiotic metabolism activities by altering constitutive and inducible levels of certain P450 and GST isozymes. PMID- 2262817 TI - Effects of fasting and refeeding on the level of uncoupling protein mRNA in rat brown adipose tissue: evidence for diet-induced and cold-induced responses. AB - Brown adipose tissue (BAT) is characterized by the existence of a unique mitochondrial protein (uncoupling protein or UCP) that uncouples oxidative phosphorylation and thus allows heat production. Its role in thermogenesis has been emphasized in recent years in response to cold stress (nonshivering thermogenesis, NST) as well as to hyperphagia (diet-induced thermogenesis, DIT). The present work was a first attempt to determine whether varying nutritional conditions could affect UCP gene expression. Total RNA was isolated from interscapular BAT and hybridized with a cDNA probe for UCP. Changes in UCP mRNA level were studied in rats fasted and refed for various periods at 23 or 28 degrees C. A 2 d fast at 23 degrees C reduced UCP mRNA level, whereas refeeding increased it. A prolonged starvation (53 h) induced an unexpected rise in UCP mRNA, which was associated with a fall in body temperature. Increasing the ambient temperature to thermoneutrality (28 degrees C) suppressed the fall in body temperature as well as the rise in UCP mRNA, which could then be characterized as a cold-induced response. Under the same environmental conditions (28 degrees C), refeeding still triggered a sharp, though transient, increase in UCP mRNA, showing that DIT was dissociated from NST. PMID- 2262818 TI - The Medical Review Officer. AB - An essential part of a carefully designed drug testing program is the Medical Review Officer's review of chain-of-custody forms and laboratory results. A positive drug test result does not necessarily identify a substance abuser. Federal drug testing regulations require that positive test results be reviewed and interpreted by the Medical Review Officer. Technical and administrative procedures can assure confidentiality and virtually eliminate the chance of persons being wrongfully characterized as using illicit substances. PMID- 2262819 TI - Evaluating the patient-handling tasks of nurses. AB - Nurses, nurses' aides, and orderlies are among the occupational groups at highest risk for back injury. The Kaiser Permanente Northwest Region developed a Back Injury Prevention Project (BIPP) to try to reduce the back injury rate among these groups. To obtain early data on program effectiveness, we developed an instrument, the BIPP Transfer Evaluation, to evaluate patient-handling tasks. Use of the BIPP Transfer Evaluation during the BIPP pilot study revealed a 19% +/- 5% SE (P = .0003) improvement in the quality of patient transfer in the intervention group. The BIPP Transfer Evaluation is an inexpensive way to get early, objective information about the quality of an intervention to reduce back injuries among nurses, nurses' aides, and orderlies. PMID- 2262820 TI - When employees kill other employees: the case of Joseph T. Wesbecker. AB - On the morning of Sept 14, 1989, Joseph T. Wesbecker, an emotionally disturbed employee on long-term disability leave from the Standard Gravure Company in Louisville, KY entered the plant in downtown Louisville and killed eight coworkers and injured 12 others with a semiautomatic "assault" rifle before taking his own life with a pistol. In this paper, the facts surrounding Wesbecker's life and the events leading up to the tragedy were examined to determine the degree of "fit" to Dr John Monahan's model for the prediction of violent behavior. Although several of the 10 predictors identified by Monahan demonstrated validity, several others did not. The Wesbecker case underscores both the difficulty in predicting violence and the challenges that occupational mental health professionals face in minimizing acts of violence in the workplace. PMID- 2262821 TI - Violence in the workplace. PMID- 2262822 TI - An immunologic and genetic study of asthma in workers in an aluminum smelter. AB - The cause or causes of asthma among employees in aluminum smelters is unknown. We attempted to ascertain whether such workers who developed asthma differed in respect to indices of immunological function and certain genetic markers. Data were collected from 33 asthmatic and 127 nonasthmatic potroom workers. Asthmatic workers had significantly lower mean serum levels of immunoglobulin (Ig)M; however, mean levels of IgG and IgA, median levels of IgE, the capacity for recall of delayed type hypersensitivity, levels of immune complexes, and frequency of antinuclear or other autoantibodies did not differ from values for nonasthmatic workers. Asthma was found to develop on a background of atopy in 21 workers (64%), whereas there were no features of atopy in 12 workers (36%). Cigarette smoking had independent effects on immunological function. In respect to genetic markers, there was a higher frequency among asthmatic workers of the alpha-1-anti-trypsin deficiency phenotype MS, but the frequency of blood groups, Gm allotypes, or human leucocyte antigen types was similar. The study established that the profile of immune function, or genetic markers tested, did not differ essentially for workers in an aluminum smelter who did or did not develop asthma; however, there was an indication of heterogeneity in causation, as judged by "atopy-related" and "non-atopy-related" groups in the asthma population. PMID- 2262823 TI - Medical screening, surveillance, and the prevention of occupational disease. PMID- 2262824 TI - An examination of occupational medicine practices. AB - The traditional occupational health on-site utilization of physicians as part of an overall occupational health program has been in decline in recent times. The on-site practitioner is increasingly being replaced by physicians who practice at an off-site location. The effects of this change on the health care delivered to the work force are largely unknown. By utilizing data from the 4490 facilities surveyed during the National Occupational Exposure Survey, it was possible to perform analyses of the association between the on- and off-site practice of medicine and several industrial facility characteristics and services usually associated with occupational medicine. Examination of the data indicated that, in comparison with on-site activity, the off-site practice of occupational medicine appears to result in diminished provision of the screening tests and medical examinations for which data were available. PMID- 2262825 TI - Effect of exercise level on ventilatory adaptation to respirator use. AB - The effect of exercise on the adaptation to an air-purifying respirator type load (dead space + inspiratory resistance) was studied in a group of 13 volunteers with a rapidly incremental exercise protocol. The difference between loaded and unloaded breathing at each exercise level was determined for each subject for a series of parameters describing the ventilatory work to overcome the respirator load pattern of breathing and metabolic work. Linear regression and t tests determined the average effect of the respirator load and the extent to which this effect was affected by the level of exercise. The inspiratory time and duty cycle were increased by the load, and exercise did not significantly affect the magnitude of this adaptation. High exercise did, however, increase the magnitude of the effect of the respiratory load on ventilatory work. These findings suggest that constraints to respiratory pattern adjustment, which may decrease respirator tolerance, occur at high exercise levels. PMID- 2262826 TI - Aggressive early medical management. PMID- 2262827 TI - Effect of a comprehensive health promotion program on employee attitudes. AB - A 2-year study was conducted to evaluate the effect of a health promotion program on the work-related attitudes of employees. The study employed a quasi experimental design with nonequivalent control groups. The change in employee attitudes at companies that participated in the program was significantly greater and more favorable than that found at nonparticipating companies. Significant change was found on attitudes toward organizational commitment, supervision, working conditions, job competence, pay and fringe benefits, and job security. PMID- 2262828 TI - Occupational medicine specialists in the United States: a survey. AB - Although a shortage of occupational medicine experts has been suggested, no accurate enumeration of actively practicing physicians who are Board-certified in occupational medicine is available. A survey of all such physicians and recent occupational medicine residency graduates was conducted to determine practice type and level of activity. Older physicians tended to practice in industry-based settings, whereas younger physicians were more likely situated in clinic settings serving a variety of employees. Projecting from our responses, we estimate that about 650 occupational medicine specialists were actively practicing at the time of the survey and that about half are available to the community physician for consultation. Fewer than two thirds of recent residency graduates had pursued Board certification; this trend will lead to a gradual decline in the number of Board-certified occupational physicians. PMID- 2262829 TI - Epidemiology of depression and alcohol abuse/dependence in a managerial and professional work force. AB - Detailed clinical interviews focusing on depression and alcohol abuse/dependence were conducted with 1870 managers and professionals drawn from a major US corporation. Among men, the lifetime and 1-year prevalence rates of DSM-III-R major depression were 23% and 9%, respectively. Among women, the rates were 36% and 17%, respectively. Lifetime and 1-year prevalence rates of DSM-III-R alcohol abuse/dependence were 16% and 4% for men, and 9% and 4% for women. Imposing a requirement that alcohol-related symptoms cluster together in time reduced the lifetime and 1-year prevalence rates to 11% and 3% for men and 5% and 2% for women. The odds ratio for the lifetime occurrence of depression and alcohol abuse/dependence with such clustering was 2.28. The three most important risk factors for depression were being female, separated or divorced, and having a family history of depression. For alcohol abuse/dependence, the most important risk factors were being male, unmarried, and having a family history of alcoholism. Manager/professional status, length of employment, hours worked per day, and supervisory responsibility were not statistically associated with either DSM-III-R major depression or alcohol abuse/dependence. PMID- 2262830 TI - Is pesticide use related to the risk of primary lung cancer in Saskatchewan? AB - Ascertaining cases from a population-based tumor registry in which registration of primary lung cancer is virtually complete, we have consistently found that 40% to 50% of male lung cancer patients were farmers. We interviewed 273 newly diagnosed men and compared their occupational exposures, medical history and smoking characteristics to those of 187 male randomly selected community control subjects. We found that more of the control subjects were farmers (53.5% v 41.4%), that the control subjects tended to have larger farms (P less than .05), and that more control subjects spilled chemicals on their hands or clothing (47% v 28%, P less than .01) and had an accidental inhalation of a chemical directly into the lung (54% v 33%, P less than .005). We report an absence of correlation of lung cancer risk with occupational exposure to any specific pesticide or pesticides grouped by chemical composition. Adjusting for smoking pack-years or extent of pesticide use did not alter our preadjustment conclusions. PMID- 2262831 TI - Do infants need nucleotide supplemented formula for optimal nutrition? PMID- 2262832 TI - Home-based therapy for diarrhea. PMID- 2262833 TI - Endoscopic and histologic findings in the upper gastrointestinal tract of children with Crohn's disease. AB - In an attempt to define endoscopic and histologic changes suggestive of upper gastrointestinal Crohn's disease (CD), the medical histories, endoscopic reports, and biopsies were reviewed from 24 pediatric patients with CD and 28 age-matched patients without CD in whom esophagogastroduodenoscopies were performed because of upper GI symptoms. No differences in the overall frequency of endoscopic abnormalities were found between the two groups. However, gastric erosions and ulcerations were more frequent in CD patients. Histological abnormalities in the stomach and duodenum were also more frequent in CD patients. Noncaseating granulomas were found in five patients with CD and in one patient without clinical, radiologic, or endoscopic evidence of CD. Focal inflammation in the stomach and duodenum occurred more frequently in CD patients. Two patients with CD had focal and deep chronic inflammatory infiltrates in the esophagus, which reached the submucosa. Abnormal histology was often seen in CD patients with normal endoscopic appearances. We conclude that superficial ulcerations seen during endoscopy and the histological finding of focal inflammation may represent upper GI CD in pediatric patients. Histological changes can be missed if biopsies are not taken from normal-appearing mucosa during endoscopy. PMID- 2262834 TI - Pathogenesis of small-intestinal mucosal lesions in chronic diarrhea of infancy: I. A light microscopic study. AB - In an effort to increase our understanding of the pathogenesis of chronic protracted diarrhea in infants, we examined 44 jejunal mucosal specimens. Only 3 of the 44 specimens showed a normal mucosa (grade 1). Partial villous atrophy was seen in 17 mucosal specimens (grade 2) with marked patchiness in all of the specimens. Subtotal or total villous atrophy (grade 3) was found in the remaining 24 mucosal biopsies. Plasma cells and macrophages were variably increased and intraepithelial lymphocytes were moderately increased in grades 2 and 3. Eight of ten mucosal biopsy specimens embedded in plastic material and cut at 1-2-mm thickness, showed bacteria of unidentified nature, situated either above the microvillous layer or on the mucosal surface. Both adherent and nonadherent bacteria could be identified in the same specimen. We concluded that severe pathological mucosal changes are common in young infants with protracted diarrhea and that the presence of bacteria may be more common than has previously been documented. PMID- 2262835 TI - Pathogenesis of small-intestinal mucosal lesions in chronic diarrhea of infancy: II. An electron microscopic study. AB - Our electron microscopic study of biopsies taken from 10 infants with protracted diarrhea was conducted in an effort to determine the pathogenesis of the disorder. In this article, the ultrastructure of the jejunal mucosa of the infants is described in relation to overlying or adherent bacteria of unidentified type. In addition to the known changes on the enterocyte surface caused by adherent bacteria (cupping and effacement), other cytopathic changes, not previously reported, are documented. Included are widespread loss of enterocytes, including intraepithelial lymphocytes, into the bowel lumen; cytopathological changes within the enterocytes; and marked thickening of the basal laminae of the enterocytes and the endothelium of lamina propria blood vessels. In addition, we noted deposition of collagen fibrils in the lamina propria below the basal laminae, active phagolysis within macrophages, and lack of cisternal material (immunoglobulin) in the plasma-cell cytoplasm. Although these changes are nonspecific, they may be related in part to the presence of the nonadhering and adhering bacteria, and their identification may further our understanding of the "sick mucosa" that occurs in chronic diarrhea of infancy. PMID- 2262836 TI - Influence of cow's milk proteins and gluten on human duodenal mucosa in organ culture. AB - Forty-five duodenal biopsies from 33 children and 3 adult patients were maintained in organ culture for 24 h and exposed to various cow's milk proteins and gluten. In 10 of 11 celiac patients with a flat duodenal mucosa, and in 2 of 4 patients with partial villous atrophy, a significant reduction in the mean enterocyte height was found after in vitro gluten exposure, compared to culture in basic culture medium. Three patients had coexisting celiac disease and cow's milk protein intolerance. alpha-Lactalbumin and beta-lactoglobulin exhibited toxic effects on flat biopsies from two of these patients, and casein was toxic in one. In 10 patients with cow's milk protein intolerance, a significant reduction in enterocyte height was noted in one case with gluten, and in three patients with casein and lactoglobulin, whereas lactalbumin did not affect the tissues. In seven control patients having a normal duodenal mucosa, no in vitro influences were noted, whereas in four patients with partial villous atrophy, a toxic reaction to gluten was seen in one and a reduced enterocyte height was seen after lactoglobulin exposure in another. In vitro toxicity induced by gluten corresponded well with the diagnosis of celiac disease, whereas toxic reactions to cow's milk proteins during organ culture were inconsistent in cow's milk intolerance, except for cases in which a marked enteropathy was documented. PMID- 2262837 TI - Lactose maldigestion: increased age-related prevalence in institutionalized children. AB - A study was performed to determine whether the age-related prevalence of lactose maldigestion is increased in healthy institutionalized children. Previous malnutrition did not exclude children from study. The control children had no prior history of malnutrition or hospital admissions for diarrhea. The anthropometric comparison showed the institutionalized children to be shorter and lighter than the controls, but they were of normal weight by stature, suggesting a normal recent nutritional state. Fasting breath hydrogen tests were performed following an oral dose of lactose 1 g/kg, given as a 10% solution. A rise of breath hydrogen of greater than or equal to 20 ppm was considered to indicate lactose maldigestion. Twenty-two of 44 controls and 39 of 49 study children were lactose maldigesters (p less than 0.01). The control children showed an age related increase in the prevalence of lactose maldigestion, from 31.6% at age less than 5 years to 75% at age greater than 9 years. The institutionalized children, by comparison had an increased prevalence of 78.8% in the group under 5 years of age (p = 0.002). Equally high prevalence rates were found at all ages tested. At follow-up, lactose maldigestion was persistent in the majority of the study children. This had no nutritional impact despite a regular milk intake. The distinction between acquired and primary lactose maldigestion is of no practical significance in these children. PMID- 2262838 TI - Usefulness of immunocytochemical demonstration of neuron-specific enolase in the diagnosis of Hirschsprung's disease. AB - The work reported here was carried out to study the importance of immunocytochemical staining of neuron-specific enolase (NSE) in the diagnosis of Hirschsprung's disease and to compare its results with those obtained by hematoxylin-eosin (H&E) staining in consecutive sections. A retrospective study was made on 51 rectal mucosal biopsies and 19 colorectal surgical specimens from 52 patients clinically suspected of Hirschsprung's disease. Several consecutive sections from all cases were restained by H&E and for NSE demonstration. Sixteen (31%) patients had a histological diagnosis of Hirschsprung's disease, 9 (17%) had hypoganglionosis, 4 (8%) had neuronal intestinal dysplasia, and 2 (4%) had normal histology. In eight patients (15%) hypoganglionosis remained dubious, and in 10 (19%) the diagnosis was inconclusive. Although the NSE staining improved the identification of the nervous tissue of the colon, both H&E and NSE staining proved to be of equal value in the assessment of the presence of neurons in the rectal wall of people with clinically suspected cases of Hirschsprung's disease. Ten H&E-stained sections from different levels of the biopsy specimen would be enough to detect ganglion cells in most cases. PMID- 2262839 TI - Cisapride for intractable constipation in children: observations from an open trial. AB - Twelve patients with chronic constipation refractory to the vigorous use of emollients, enemas, and/or laxatives were chosen for study of the investigational prokinetic agent, Cisapride. The patients included 8 boys and 4 girls with diagnoses of functional constipation. Ages ranged from 2 to 13 years; duration of symptoms before Cisapride use ranged from 1.5 to 9.75 years; duration of previous treatment ranged from 0.75 to 6 years. The mean number of doses of anticonstipation agents employed per week was 14. Of the 12 patients, 10 had persistent encopresis, while 11 required hospitalization for disimpaction an average of 1.6 times in the year prior to Cisapride use. Three had chronic urinary tract complaints. Anal manometry suggested a sensory deficit in 8 of 10 patients tested. Ganglion cells were identified by rectal biopsy in all 12 patients. Cisapride treatment (0.14-0.3 mg/kg/dose) spanned 26-72 weeks (61 +/- 12). Stool frequency per week was not significantly changed, but five of seven patients who had reported hard stools had softer stools on the drug (p less than 0.05). Encopresis ceased in 8 of 10 cases, while the number of episodes decreased substantially in the other 2 cases (p less than 0.05). All alternate forms of anticonstipation therapy were withdrawn in 8 of 12 cases (p less than 0.001). Urinary problems improved in two of the three patients reporting symptoms. One patient showed no improvement in any parameter while on the agent, despite 26 weeks of administration. Side effects were infrequent, generally occurred early, and were limited to cramping, nausea, mild vomiting, anorexia, and headaches. One patient ceased use of the drug for persistent headaches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262840 TI - Effect of feeding yogurt versus milk in children with persistent diarrhea. AB - Although the pathophysiology of persistent diarrhea in children remains unclear, it has been suggested that it may be related to the composition of the food ingested. Since lactase deficiency and cow's milk protein intolerance are often identified in children with persistent diarrhea, replacement of milk with yogurt should be beneficial. We, therefore, compared the clinical outcome of children (aged 3-36 months) with persistent diarrhea randomly assigned to receive either milk or yogurt for 5 days. Preliminary results on 45 of the 100 children indicated clinical failure, which was determined after a 5% loss of body weight per day or the persistence of diarrhea after 5 days, in only 14% of the children fed yogurt compared to 42% of those fed milk (p less than 0.05). These preliminary results strongly suggest a clinical advantage of feeding yogurt rather than milk in children with persistent diarrhea. PMID- 2262841 TI - Choledocholithiasis in infants: diagnostic and therapeutic problems. AB - During the 3-year period, January 1986 through December 1988, 7 of 24 infants evaluated for cholestatic liver disease were found to have choledocholithiasis with or without associated gallbladder disease. Five were born prematurely with associated predisposing factors, especially systemic infection and total parenteral nutrition. The clinical course varied from spontaneous recovery in two patients to ongoing liver disease requiring surgical or endoscopic intervention in five infants. Asymptomatic patients with normal liver function and persistently dilated extrahepatic biliary trees posed the most difficult therapeutic problems. Endoscopic retrograde cholangiography appeared to be an effective and rewarding therapeutic approach. PMID- 2262842 TI - Kupffer cell engraftment across the major histocompatibility barrier in mice: bone marrow origin, class II antigen expression, and antigen-presenting capacity. AB - The source of population renewal for Kupffer cells (KC), the major antigen presenting cells of the liver, remains controversial. Using a well-described murine bone marrow transplantation (BMT) model in which the donor and recipient are disparate at the major histocompatibility complex (MHC), we have studied (a) the source of KC renewal by genotypic analysis, cell surface (class II or Ia) antigens, and immune function assays; (b) the level of KC Ia expression post-BMT in transplant recipients; and (c) the capacity of newly repopulating KC to present antigen to an Ia-restricted T cell clone of donor Ia type. Kupffer cell engraftment, as assessed by each of these three methods, was noted to be predominantly of donor marrow origin by day 21 post-BMT. Cell surface Ia expression was comparable to that of nontransplanted controls of the same strain as donor mice. Within 7 days post-BMT, KC were mature antigen-presenting cells. We conclude that KC rapidly repopulate the liver from donor bone marrow post-BMT, and these macrophages are able to interact with T lymphocytes in an immunocompetent manner. PMID- 2262843 TI - Intussusception of the appendix in a patient with cystic fibrosis. AB - This case report describes the clinical presentation and the radiographic, endoscopic, and pathologic findings in a patient with cystic fibrosis (CF) and intussusception of the appendix. This is the first time that intussusception of the appendix has been documented in a patient with CF. This disorder should be considered in the CF patient with cramping lower abdominal pain or rectal bleeding. PMID- 2262844 TI - Hepatomegaly as a single presenting sign of stage IV-S neuroblastoma. AB - This article presents the case of an infant who on routine physical examination at the age of 5 months was found to have hepatomegaly. The initial investigation revealed borderline liver function tests, and ultrasonography showed multiple space-occupying lesions. Further workup using different imaging techniques, urinary vanillylmandelic acid, serum catecholamines, and liver biopsy led to the diagnosis of stage IV-S neuroblastoma. No primary site outside of the liver could be demonstrated. The tumor regressed spontaneously. PMID- 2262845 TI - Halothane hepatitis in children. AB - Halothane hepatitis is now a well-recognized distinct entity in adults, but there prevails an often-taught "axiom" that halothane hepatitis "does not occur" in children. We describe 2 children who developed cholestatic hepatitis following halothane anesthesia. The first patient had no antecedent liver disease, and presented with anorexia, abdominal pain and delayed onset of jaundice after multiple halothane exposures. Halothane-specific antibodies were positive, and liver tests resolved completely. The second patient had antecedent liver disease and presented with delayed onset of unexplained high fevers for 10 days following a single halothane exposure. Gradually increasing cholestasis ensued in the absence of other causes of liver disease. Halothane antibodies were negative. These cases illustrate different clinical presentations of halothane hepatitis, such as delayed onset of jaundice or fever following halothane exposure. The difficulties in making a definitive diagnosis and the need to exclude other causes of liver disease are detailed. Risk factors and other presentations are discussed. While halothane hepatitis appears to be an uncommon entity in children, it does occur, and may present with manifestations less than fulminant hepatic failure. A high index of suspicion and a detailed history of the time sequence of events are necessary as the diagnosis is primarily clinical. Halothane-specific antibodies are helpful if positive. In any child developing unexplained jaundice or high fevers following halothane anesthesia, further exposures should be avoided and halothane-specific antibodies obtained. PMID- 2262846 TI - Necrotizing perianal infection and proctitis in an infant. PMID- 2262847 TI - Gallstone pancreatitis in a fifteen-year-old girl. PMID- 2262848 TI - Antibiotic prophylaxis of cholangitis after the Kasai procedure. PMID- 2262849 TI - Papers presented at the 38th annual meeting of the Surgical Section of the American Academy of Pediatrics. Chicago, Illinois, October 21-23, 1989. Part 3. Proceedings. PMID- 2262850 TI - Gastrostomy with antireflux properties. AB - The need for feeding gastrostomy seems to be increasing in children with neurological impairment and swallowing incoordination. Because gastrostomy can cause or increase gastroesophageal reflux, an antireflux procedure has been advocated at the time of gastrostomy placement in neurologically impaired children. A gastrostomy in the lesser gastric curvature with antirefluxing properties was performed in nine neurologically impaired children. All had severe swallowing incoordination with aspiration and malnutrition. Postoperatively none of the nine patients have demonstrated clinical evidence of vomiting or gastroesophageal reflux. This type of gastrostomy prevents the developement of gastroesophageal reflux by increasing the length of the intraabdominal esophagus and by increasing the acuity of the gastroesophageal angle of His. When compared with an antireflux procedure, it has less complications, shorter postoperative recovery, and is more economical. PMID- 2262851 TI - The failed antireflux procedure: analysis of risk factors and morbidity. AB - Between 1976 and 1988 an antireflux procedure (ARP) was performed in 364 infants and children (Nissen, 358; Thal, 6). Recurrent gastroesophageal reflux (GER) necessitating reoperation occurred in 21 patients, a failure rate of 6%. Recurrent GER developed within 28 months of primary ARP in 18 (86%) children. The symptoms of GER became apparent following an episode of forceful emesis in 29% of patients, half of whom had a malpositioned gastrostomy tube. Recurrent GER developed in 28% of children with corrected esophageal atresia. A definitive etiology of ARP failure was identified in 18 (86%) cases: "slipped" fundoplication (15), no fundoplication visualized (2), and paraesophageal hernia (1). Perioperative morbidity, intraoperative blood loss, and length of surgery were significantly increased for secondary ARP. Mortality following reoperation was zero, but three late deaths occurred. Long-term control of GER has been achieved in 78% of children following the second operation. PMID- 2262852 TI - Therapeutic and diagnostic implications of acquired choledochal obstruction in infancy: spontaneous resolution in three infants. AB - Three infants aged 2 days to 11 weeks with conjugated hyperbilirubinenemia, had sonographically documented dilated common hepatic bile ducts, and echogenic material in the gallbladder. A 2-day-old infant, born to a diabetic mother, had none of the classic predisposing factors for cholelithiasis, and two infants had received total parenteral nutrition (TPN) and TPN plus furosemide. The first infant after receiving 4 1/2 weeks of TPN and furosemide, developed common duct obstruction with increasing bilirubin and hepatic duct caliber over a 12-day period. An operation was scheduled; however, on the following day the bilirubin dropped abruptly and surgery was canceled. The experience with this infant encouraged conservative management in two subsequent infants with similar clinical and sonographic findings. Spontaneous resolution occurred 9 days after the onset of common duct obstruction in one infant and after 16 days in the other. PMID- 2262853 TI - A 13-year experience with peritoneal drainage under local anesthesia for necrotizing enterocolitis perforation. AB - Between 1974 and 1986, inclusive, over 400 newborns with clinical, radiological, and/or pathological evidence of necrotizing enterocolitis (NEC) were treated at the Hospital for Sick Children, Toronto, Ontario. Within this group were 37 babies who had a bowel perforation that was treated with peritoneal drainage under local anesthesia. Eighty-eight percent of the 41 weighed less than 1,500 g and 65% weighed less than 1,000 g; during the same time 40 other neonates (9% of the total) with perforated NEC had laparotomies. Twelve neonates (32%) required only drainage with complete recovery of their intestinal tracts. The remaining 25 (68%) fell into one of three groups: (1) nine (24%) had rapid downhill course, sepsis, and death without laparotomy; (2) nine (24%) had rapid downhill course, sepsis, and laparotomy (five deaths); (3) seven (20%) had slow development of bowel obstruction requiring operation (two deaths). The overall survival rate was 56%. These results continue to indicate that this method is effective in temporizing 88% of the small and/or very ill babies with a NEC perforation. However, an added bonus is that 32% of these newborns treated in this fashion had complete resolution of their disease. PMID- 2262854 TI - Failure of percutaneous drainage in children with traumatic pancreatic pseudocysts. AB - Recent reports have documented the successful use of percutaneous drainage (PD) in the management of traumatic pancreatic pseudocysts in children. This study presents four cases of pancreatic pseudocyst in which percutaneous catheter drainage was performed. In one instance, no operative therapy was required. However, in the other three cases PD failed to resolve the problem and distal pancreatectomy with splenic salvage was performed when contrast studies (endoscopic retrograde cholangiopancreatography or catheter injection) demonstrated disruption of the main pancreatic duct. This report suggests that children with pancreatic pseudocysts unresponsive to PD require prompt investigation of ductal anatomy to rule out transection or other major injury. PMID- 2262855 TI - Congenital diaphragmatic hernia repair on ECMO. AB - Congenital diaphragmatic hernia (CDH) with severe respiratory failure in the first few hours of life continues to be associated with significant mortality. Extracorporeal membrane oxygenation (ECMO) has been successfully used postoperatively to reverse the effects of severe pulmonary hypertension. Since 1984, ECMO has been required in 27 of the patients we treated with CDH. This report describes our experience with six very high-risk patients placed on ECMO prior to the operation who subsequently underwent repair of their diaphragmatic hernias while on ECMO. Two patients presented in extremis, unlikely to survive initial operative repair, and were placed on ECMO prior to the operation. All six patients had immediate respiratory distress after birth with mean Apgars of 2.3 and 3.7. The best pre-ECMO arterial blood gas (postductal) showed mean +/- SEM values of 6.97 +/- 0.1; PO2 = 54.8 +/- 5.9; PCO2 = 79.5 +/- 16.9. Immediately prior to ECMO, the mean +/- SEM ventilatory index (VI = rate x mean airway pressure) was 1,233 +/- 44, with a mean pH of 7.17 +/- 0.05; PO2 = 32 +/- 2.9; PCO2 = 59 +/- 5.3 and a mean AaDO2 of 622 +/- 4.8. The timing of the operative repair averaged 25 hours following initiation of ECMO. Three right-sided and three left-sided hernias were treated. Four were repaired through an abdominal approach, and two via thoracotomy; four required a Gortex patch closure. Postoperative bleeding was not a major problem in these heparinized patients. Four of these six patients survived, and follow-up of 2 months to 3 years shows no significant respiratory compromise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262856 TI - Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: should any infant be excluded? AB - Mortality in infants with congenital diaphragmatic hernia (CDH) remains high despite improvements in neonatal and surgical care because many infants develop persistent pulmonary hypertension of the newborn (PPHN) following repair. Since 1984, extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in all infants (n = 25) with PPHN following CDH repair when conventional management failed, with an overall survival of 60%. Repair was performed in this hospital on 12 infants and in other hospitals in 13 infants transferred for consideration of ECMO after repair. Mortality was the same in the group repaired here and those transferred for ECMO. Although complications were frequent in the surviving group, they were successfully managed with nonoperative or operative therapy. Selective use of ECMO has been advocated in CDH patients based on various predictors of high mortality such as "best" PO2 postrepair less than 100 mm Hg, oxygenation index greater than 40, and ventilation index greater than 1,000 with PCO2 greater than 40. Seven surviving infants following ECMO would have been classified as unsalvageable by at least one parameter if selection criteria based on these parameters had been used. We conclude from this series that current predictors of high mortality in CDH patients are unreliable when ECMO is used. Surgeons caring for infants with CDH should consider the use of ECMO in all infants. PMID- 2262857 TI - Pulmonary hypertension in neonatal cystic lung disease: survival following lobectomy and ECMO in two cases. AB - Extracorporeal membrane oxygenation (ECMO) is an accepted form of therapy in the treatment of neonates with otherwise lethal persistent pulmonary hypertension related to meconium aspiration, congenital diaphragmatic hernia, and sepsis. This report concerns two neonates with congenital cystic lesions of the lung who developed severe pulmonary hypertension and were salvaged with lobectomy and ECMO. These cases present an additional group of patients in whom ECMO may be a life-saving measure. PMID- 2262858 TI - Pancreatic tumors in childhood: analysis of 13 cases. AB - Pancreatic tumors are rare in children. Over a 20-year period we have treated 13 children with pancreatic neoplasms. There were eight boys and five girls (age range, 4 months to 12 years). Seven tumors were benign, including five insulinomas, and two cystadenomas. Six lesions were malignant (rhabdomyosarcoma, 2; pancreatic carcinoma, 4). Children with insulinoma presented with hypoglycemia and irrational behavior. Three had abnormal insulin:glucose ratios ( greater than 1.0). The tumor was detected by computed tomography scan in three cases, at the time of surgery in one, and with intraoperative ultrasound in one. Surgical treatment included tumor enucleation in four cases and 80% pancreatectomy in one. Mucinous cystadenomas were observed in two patients, ages 4 months and 10 months. Tha latter infant underwent cyst excision alone, resulting in malignant recurrence at 18 months of age and death. The 4-month-old child had a distal pancreatectomy and is alive at 6 years. Two of the four children with pancreatic cancer had unresectable tumors at diagnosis, and were treated by biopsy (ductal adenocarcinoma), irradiation, and chemotherapy. Length of survival was 6 months and 9 months. Two others (ages 4 and 12 years) underwent 85% distal pancreatic resection for pancreatoblastoma and a pancreatoduodenectomy for papillary carcinoma, respectively. The latter is alive and tumor-free at 20 years of follow up. The former underwent hepatic lobectomy for a 3.0 x 3.0 cm solitary liver metastases and is alive at 6 years with no evidence of disease. One child with rhabdomyosarcoma died of progressive disease, the other is alive with residual disease despite resection and chemotherapy. Most insulinomas can be treated by enucleation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262859 TI - Recurrent pheochromocytomas in children. AB - Between 1958 and 1987, 13 children (aged 8 to 17 years) with 20 pheochromocytomas were diagnosed and treated. Five of these 13 had multiple (12) tumors and four patients had five recurrences in 6 years (1980 to 1986). There were three girls and one boy between 8 and 15 years of age. One girl had von Hippel-Lindau disease. Three of four original tumors were adrenal and less than 6 cm in diameter. All were excised without complications and went home normotensive. The five recurrent tumors were diagnosed and treated within 6 years of the original tumor when the children were 9 to 17 years; their presenting symptoms and signs (3 months) were hypertension plus others, not necessarily the same as previously. Computed tomography scan was again positive in the three that had this test; vanillylmandelic acid was the only uniformly positive biochemical test. Norepinephrines were positive in the three patients examined. The three girls had their recurrent tumors found in the opposite adrenal and the boy once again had two more tumors (adrenal and chest); all tumors were less than 3 cm in diameter and easily excised. They remain normotensive and well up to 8 years. Within this small group of recurrences, there was no specific pattern that would have led one to suspect that they would return with another pheo. There was nothing unusual about their recurrent tumor, except that it was usually in the opposite adrenal; only one of the four children has no remaining adrenal tissue. Although follow-up is important, recurrent pheochromocytomas seem to be heralded by recurrent symptoms and signs of hypertension. PMID- 2262860 TI - Prognostic factors in bladder and bladder-prostate rhabdomyosarcoma. AB - In order to examine surgical factors predictive of fatal outcome in patients presenting with histologically verified rhabdomyosarcoma of the urinary bladder, we performed a retrospective analysis of cases presenting between the years 1970 and 1985 and treated by protocol. Twenty-five patients were identified and data were complete for univariate and multivariate analysis on all. Staging was done according to the criteria of the International Union Against Cancer (TNM). Median age at presentation was 14.7 years and 10 patients were younger than 10 years. Median follow-up was 4.8 years overall and 8.4 years in survivors. Four patients presented with involvement of regional lymph nodes and three with distant metastases. Complete surgical resection, defined as negative microscopic margins, was accomplished by total cystectomy in 14 patients, and partial cystectomy in two. In this group cystectomy was performed prior to chemotherapy and radiation in five and after in 10 (persistent disease). Three salvage cystectomies were performed in patients who recurred after initial complete responses to chemotherapy and radiation therapy. Thirteen patients received a median of 3,000 cGy (range, 1,800 to 5,000 cGy) of external beam pelvic irradiation, and two received brachytherapy. All patients received multiple agent chemotherapy according to either the T2 or T6 protocol. There are 11 disease-free survivors (44%) and 10 of these have been followed for more than 6 years. One patient is alive with disease 6.5 years after diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262861 TI - Carcinoid tumor of the appendix in the first two decades of life. AB - Carcinoid tumor of the appendix is the most common neoplasm of the gastrointestinal tract in childhood and adolescence. Sufficient long-term follow up data after surgical treatment are not currently available for patients diagnosed during the first two decades of life. From 1936 to 1988, 23 patients were observed at this institution with histologically confirmed carcinoid tumors involving the vermiform appendix. In contrast to the adult experience, in which the tumor is most commonly encountered as the result of an incidental appendectomy, 18 of these patients presented with signs and symptoms of an acute abdomen directing the surgeon to the appendix. In the other five cases, surgery was performed for other reasons. Median age at presentation was 13.0 years (range, 6 to 20 years). Fourteen patients were female, nine were male. Simple appendectomy was the initial procedure for all patients. Tumor size ranged from "microscopic" to 2.5 cm in largest dimension. Three patients subsequently underwent right hemicolectomy, and one patient had removal of a residual appendiceal stump, but no residual or metastatic tumor tissue was found in any of the resected specimens. Nineteen patients underwent simple appendectomy alone. Eighteen available specimens were reviewed at the time of this study for confirmation of histology and degree of invasion. The tumor invaded to the serosa in nine of 23 (39%). The mesoappendix or periappendiceal fat was involved in seven of 23 (30%). Vessel invasion was not noted in any specimen. Our median follow-up time was very long, being 26 years (range, 9 months to 51 years). No patient has had evidence of recurrent or metastatic disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262862 TI - Biliary atresia registry, 1976 to 1989. AB - The Registry provides information about 904 children with biliary atresia from more than 100 institutions. There was a 1.4 to 1 female predominance; racial distribution was 62% caucasian, 20% black, 11% Hispanic, 4.2% asian, and 1.5% American Indian. Eight hundred sixteen (90%) underwent corrective surgery (median age at operation, 69 days). Intraoperatively, 70% had totally obliterated extrahepatic bile ducts, 22% had patency of the gallbladder and distal common duct, whereas only 8% had "correctable" biliary atresia (proximal duct patency). A variety of reconstructions were used, but the majority of patients had a Roux en-Y portoenterostomy with or without exteriorization. Follow-up was available for 670 children (74%) with average length of follow-up of 5 years (range, 1 to 16 years). Five-year actuarial survival was 48% following Kasai's operation, but was less than 10% (at 3 years) if no operative correction was done. Survival was unaffected by sex, type of reconstruction, or cholangitis. Predictors of a bad outcome were (1) caucasian race; (2) operative age greater than 60 days; (3) presence of cirrhosis at initial biopsy; (4) totally nonpatent extrahepatic ducts; (5) absent ducts at the level of transection in the liver hilus; and (6) subsequent development of varices or ascites. Identification of factors predictive of the ultimate outcome provide a basis for either continued efforts with management of Kasai's operation or for early referral for liver transplantation. PMID- 2262863 TI - Big shunts for small patients with portal hypertension: a bit of history. AB - This is a brief resume of my personal experiences that led to the development of two portosystemic shunt procedures designed to be used in small patients with bleeding varices and portal hypertension. Both enable one to decompress the congested protal venous system in the preschool-aged group when about two thirds of such patients begin to suffer their first life threatening bleeding episodes. PMID- 2262864 TI - Pediatric surgery in Kenya. PMID- 2262865 TI - Fine-needle cytology of solid tumors: method, diagnostic accuracy, and role in management. AB - Fine-needle cytology was obtained from 14 solid tumors in 12 children. Both aspiration and nonaspiration techniques were used and several staining methods were applied. May Grunwald Giemsa and Papanicolaou stains were preferred. The nonaspiration method yielded a superior quality cytology smear with less blood contamination. There were no complications recorded. Confirmation of the diagnosis with cytology allowed for planned management with preoperative cytotoxic chemotherapy and/or radiotherapy in 10 children, immediate surgery in one, and radiotherapy to a vertebral recurrence in one. Fine-needle cytology is considered a useful technique in the management of a selected group of children with solid tumors. PMID- 2262866 TI - N-myc gene amplification and other prognosis-associated factors in neuroblastoma. AB - The correlation between N-myc gene amplification and heretofore known prognosis associated factors was studied in 23 cases of neuroblastoma, comprising a total of 29 tumors (23 primary and six metastatic), examined in and after 1983. DNAs were extracted from tumor tissues preserved at -70 degrees C and digested with the restriction enzyme EcoRI. Southern blotting analysis was performed on these DNAs with the N-myc probe labelled with alpha-32P-dCTP. Prognosis-associated factors studied were age at diagnosis, stage, primary site, histological type, blood biochemistry tests, and catecholamine metabolites in urine. Amplification of N-myc gene was observed only in the cases in which primary site was the adrenal gland, but the relation to the stage, histological type, and prognosis was not as apparent as reported by other investigators. However, the amounts of catecholamine metabolites were low in the cases with amplification, and this suggests immaturity of catecholamine metabolism in the tumor with N-myc gene amplification. PMID- 2262867 TI - Secondary surgical procedures to evaluate primary tumor status in patients with chemotherapy-responsive stage III and IV sarcomas: a report from the Intergroup Rhabdomyosarcoma Study. AB - Fifty children with clinical group III (localized, but unresected) or clinical group IV (disseminated) soft tissue sarcomas were entered in a trial to determine if the addition of etoposide and cisplatin to standard chemotherapy regimens and irradiation (4,000 cGy) would be tolerated by pediatric patients. Responding patients had a secondary surgical procedure performed after approximately 20 weeks of therapy for the purpose of establishing histological response, determining its extent, and removing residual tumor tissue, when feasible. Such procedures were performed in 29 of 50 (58%) of these patients, ie, 20 of 31 (65%) of those in group III, and nine of 19 (47%) of those in group IV. Surgical procedures consisted of exploration of the site and biopsy (only) in 16 patients; grossly complete tumor excision in nine; and subtotal tumor excision in four. In nine patients (six in group III, three in group IV) apparent total excision of a previously unresected primary tumor mass was accomplished at second surgery. One distant but no local relapse has occurred in this group, and eight of nine have survived (five of six with identified tumor in the specimen) for a duration of 232 to 348 weeks (six greater than 260 wks), suggesting that among patients with primary tumors in selected sites, with either stage III or stage IV disease, excision of residual masses following intensive chemotherapy/radiotherapy regimens may favorably influence outcome. Local relapse subsequently occurred in seven of 18 patients in whom tumor tissue could not be identified in biopsy specimens or in excised masses taken from the primary site at second surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262868 TI - Pulsed wave Doppler velocimetry in the descending aorta of chronically instrumented fetal sheep. AB - Pulsed wave Doppler sonography was used to determine peak systolic velocity (Vpeak), mean maximum velocity (Vmean) and Pulsatility Index (PI) in the descending aorta of chronically instrumented, unanesthetized fetal sheep (days 120-130 of pregnancy). Measurements were done 1-4 days after surgery using a duplex mechanical sector scanner (4.5 MHz) and offset attached pulsed wave Doppler probe (2.25 MHz) during periods of control, intrauterine cooling and rewarming. Mean values derived from the envelope curve of maximum shift frequencies were (controls): thoracic: Vmean 60.9 +/- 9.1 cm/sec, Vpeak 118.9 +/- 17.8 cm/sec, PI 1.57 +/- 0.24; abdominal: Vmean 49.6 +/- 10.9 cm/sec, Vpeak 98.9 +/- 20.4 cm/sec, PI 1.59 +/- 0.41. Vpeak was positively correlated to arterial pressure (r = 0.23) and PI showed an inverse correlation to heart rate (r = 0.22). During cold stress (reduction of fetal core temperature by 2.7 degrees C) and consecutive rewarming Vpeak and Vmean were positively correlated to fetal core temperature and arterial pressure (r = 0.2-0.26). PI revealed a weak negative dependency from core temperature and heart rate (r = -0.19 and -0.18 respectively). PMID- 2262869 TI - Uteroplacental blood flow velocity waveforms as a predictor of adverse fetal outcome and pregnancy-induced hypertension. AB - The resistance index (RI) of uteroplacental blood flow velocity waveforms (VWF) was investigated by continuous Doppler ultrasound in 286 nonselected pregnant women with singleton pregnancies at 18-21 weeks (n = 129) and at 31-33 weeks (n = 157) of gestation to evaluate the validity of this method as a screening procedure for abnormal pregnancy outcome (intrauterine growth retardation, pregnancy-induced hypertension and fetal asphyxia). The sensitivity of predicting pregnancy outcome was 26.6% at 18-21 weeks and 17.6% at 31-33 weeks of gestation. It was concluded that this method is too insensitive as a screening tool for the prediction of intrauterine growth retardation and pregnancy-induced hypertension in a low-risk nonselected pregnant population. PMID- 2262870 TI - Skeletal muscular changes in Pena-Shokeir sequence. AB - Histologic examination of the skeletal muscles in 8 fetuses and newborn patients with the Pena-Shokeir sequence revealed only minor nonspecific changes which could not be ascribed to any of the well defined myopathies. Muscle fiber diameters were increased in 2 out of 5 patients examined. No significant malformations of inner organs were found at autopsy. It is concluded that fetal hypokinesia due to skeletal muscular lesions might be responsible for both the pulmonary hypoplasia and the deformations of the face and extremities in all cases of this investigation. PMID- 2262871 TI - Intrauterine growth: association with acid phosphatase genetic polymorphism. AB - Acid phosphatase (ACP1) is an enzyme found in the cytoplasm of many tissues and probably functions as a flavin mononucleotide-phosphatase. Therefore the highest concentration of flavin-mononucleotide cofactors is expected in ACP1 phenotypes with the lowest enzymatic activity (A and BA) and the lowest concentration of these cofactors is expected in phenotypes with the highest activity (CB and C). Accordingly, metabolic activities related to flavoenzymes should attain maximal levels in A and BA phenotypes and minimal levels in CB and C phenotypes. In the present study we have analyzed possible effects of ACP1 genetic variability on intrauterine growth in a sample of 609 newborns collected from three consecutive series in Rome. An association between ACP1 and birth weight is observed. The association is present only among male infants. ACP1 phenotypes with low enzymatic activity (A and BA) show a clear tendency to higher rates of intrauterine growth. A linear negative correlation is also observed between enzymatic activity and quartile class. The relation is significant only in male infants. The data suggest that in fetuses with low ACP1 activity, metabolic activity may be regulated at a level allowing a full response to specific genetic stimuli maximizing fetal growth. PMID- 2262872 TI - Antenatal aminophylline and steroid exposure: effects on glomerular filtration rate and renal sodium excretion in preterm newborns. AB - Creatinine clearance and renal sodium excretion were measured consecutively in three groups of 12 premature infants (gestational age less than or equal to 35 weeks) whose mothers had received either steroids or aminophylline, or steroids and aminophylline before delivery. We found no significant differences for plasma and urine creatinine and its clearance in the groups considered. The steroid group presented urine osmolality and urine/plasma osmolality ratio significantly higher than among the other groups. Furthermore, urine potassium excretion increased, and urine sodium and sodium fractional excretion were reduced. Aminophylline exposure did not interfere with the hydrosaline equilibrium nor with renal function of the preterms at birth. Our results reconfirm that corticosteroid hormones play an important part in the fetal renal maturation process, inducing a precocious maturation of the tubular Na(+)-K+ ATPase enzymatic system, that is substantially unmodified by aminophylline exposure. However, due to the prolonged half-life of aminophylline in prematures, it seems reasonable to verify the coupling of tubular and glomerular functions also in the following days of life. PMID- 2262873 TI - Quantitative relationships between pain intensities during labor and beta endorphin and cortisol concentrations in plasma. Decline of the hormone concentrations in the early postpartum period. AB - In 38 women with uncomplicated vaginal delivery at term, the different pain intensities during spontaneous labor were correlated to the plasma beta-endorphin and cortisol concentrations simultaneously examined. The pain intensities subjectively assessed were numerically categorized. The women in labor categorized to pain intensities 0 to III were in comparable stages of cervical dilatation. The hormone concentrations were measured by means of radioimmunoassay. The lowest hormone levels were found after abolition of pains of labor by epidural anesthesia: beta-endorphin 42 pg/ml, cortisol 318 ng/ml (mean values). The hormone concentrations rose progressively with increasing intensities of labor pain. The highest concentrations were observed in the first few minutes after delivery i.e. immediately after cessation of the extreme pains of expulsive labor: beta-endorphin 118 pg/ml, cortisol 449 ng/ml. Statistically significant, positive correlations were calculated between beta-endorphin and cortisol concentrations in plasma and the self-reported pain intensities (p less than 0.001 and p less than 0.01 resp.). Thus, highly elevated beta-endorphin levels in plasma do not abolish pain, probably they modulate it. Within the first four hours postpartum the concentrations of the two stress-stimulated hormones dropped rapidly. The endorphin level fell from 118 pg/ml immediately after delivery to 38 pg/ml in the above mentioned period, the cortisol level from 449 ng/ml to 302 ng/ml. One to three days after delivery the beta-endorphin and cortisol concentrations in maternal plasma were largely normalized, this means they then approximately corresponded to the values being found in nonpregnant women under normal conditions. PMID- 2262874 TI - Early prediction of fetal macrosomia in diabetes mellitus. AB - We studied 374 pregnant diabetic women to determine the value of various ultrasound parameters in the prediction of fetal macrosomia. The correlation between ultrasonographic signs and maternal glycaemia in the development of fetal macrosomia was also studied. Significant correlation was observed between the accurence of hydramnios and future macrosomia during the second-trimester (p less than 0.001). Serum fructosamine levels as an index of maternal glycaemia in patients of macrosomic fetuses were significantly higher throughout the pregnancy as compared with mothers of infants with normal birth weight (p less than 0.001). These data suggest: 1. The presence of hydramnios in the second trimester is a useful predictor of macrosomia in diabetic patients (specificity: 86%, negative predictive value: 88%). 2. Maternal diabetic control during pregnancy has a significant influence on fetal growth and contributes to the development of fetal macrosomia. 3. The lack of correlation between the frequency of hydramnios and fructosamine levels suggests that a mechanism other than carbohydrate metabolism also plays an important role in the development of fetal macrosomia. PMID- 2262875 TI - Transplacental transfer of morphine in man. AB - The transplacental transfer of morphine and morphine-3-glucuronide (M3G) was studied in five cases of suspected Rh-isoimmunization. Ultrasound-guided fetal blood sampling from the umbilical vein was carried out as a diagnostic procedure before intrauterine blood transfusion. Morphine was given as a parenteral premedication to the mother at a dose of 0.13-0.20 mg/kg bw. Fetal blood was sampled 5-74 minutes after the morphine administration. These five women were investigated on 14 different occasions. The plasma concentrations of morphine and M3G were measured in blood samples collected simultaneously from mother and fetus. The feto-maternal ratio of morphine was 0.96 at five minutes and remained close to 1.0 in most samples taken later. At 12 minutes the ratio of M3G was less than 0.002 and between 0.2 and 0.6 in the later samples. The feto-maternal plasma ratios of morphine and M3G did not change over the studied period in one woman investigated five times between gestational weeks 26 and 32. This is the first time transplacental transfer of morphine has been quantified in man. Our results demonstrate a rapid transplacental passage and equilibration of morphine between mother and fetus. PMID- 2262876 TI - Antenatally diagnosed fetal hydronephrosis. Five year's follow up. AB - Over a one year period 13 fetuses with urinary tract abnormalities were detected by antenatal ultrasound. Extra-renal dilatation was found in six, in two abnormalities requiring an intervention after delivery. Intra-renal hydronephrosis was present in five cases, of which three required surgery during the neonatal period to relieve the obstruction. Other abnormalities detected were one case with unilateral multicystic kidney and one case with small dysplastic kidneys. Multicystic kidney was removed and the infant with dysplastic kidneys died soon after delivery. Our limited numbers of antenatally detected hydronephrosis will point to the early diagnosis and intervention to avoid renal damage. PMID- 2262877 TI - [Research for development of immunoassay kits for hapten]. AB - Determination of estrogen concentrations in the urine is widely utilized for a variety of purposes, such as the assessing of fetoplacental unit function and ovarian function, and the monitoring of follicle in inducing ovulation in the treatment of infertility. Since hapten antigens such as estrogen have low molecular weight, unlike high molecular substances, they do not form visible agglutination of antigen-antibody reaction, so there has been no other choice but to depend on radioimmunoassay for the determination of estrogen concentrations. However, radioimmunoassay requires special facilities and apparatus and is complicated in procedure, and these drawbacks have prevented the estrogen assay from routine tests in spite of clinical usefulness. As a result of various researches, a new immunochemical principle called competitive agglutination inhibition reaction has been developed for the determination of hapten concentrations, and succeeded in putting this principle to practical use with a fetoplacental unit function test kit (Estrotec slide test) and highly sensitive semi-quantitative analysis kits for urinary estrogen (Hi-estrotec and Hi-estrotec slide). PMID- 2262878 TI - [Studies on FK482 (Cefdinir). III. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinyl-3- cephem-4-carboxylic acid derivatives]. AB - The synthesis, antibacterial activity and oral absorption of the 7 beta-[(Z)-2 aryl-2-hydroxyiminoacetamido]-3-vinylcephalosporins (Ia--e) are described. All of these compounds exhibited excellent activity against Staphylococcus aureus. Against Gram-negative bacteria FK482 exhibited more excellent activity than the other compounds (Ia--e). These compounds except Ie showed good oral absorption. The relationship between the oral absorption rates and the lipophilicity of these cephalosporins is discussed. PMID- 2262879 TI - [Etoposide-induced deoxyribonucleic acid (DNA) damage and its effects on nucleotide pools in murine leukemia L1210 cells]. AB - The effect of etoposide-induced deoxyribonucleic acid (DNA) damage and its effect on nucleotide pools were examined in murine leukemia L1210 cells. Etoposide (15 mg/kg) was administered intraperitoneally on the third day after peritoneal inoculation of 1 x 10(6) L1210 cells. The dosage of etoposide produced 175% of the increase of lifespan as described previously. Strand breaks in DNA occurred within 10 min after i.p. injection, but as the time interval between injection and removal of the cells from the mice was elongated to 1 and 3 h, the continuous repairing of DNA was observed. At 6 h after the injection, the maximum concentration of DNA was located in the vicinity of that of control. In our previous study, ara-C was most effective when given at 3 to 6 h after the administration of etoposide. The sensitivity to ara-C might increase during the repairing period from the etoposide-induced DNA damage. All four dNTPs increased progressively within 6 h up to 3-fold of control. The changes in rNTPs were similar, but the degree of the changes was smaller than that of dNTPs. These changes in dNTPs and rNTPs would be an important factor for the combination to determine the antitumor effect of etoposide and nucleoside analogues. PMID- 2262880 TI - [Augmentation of pirarubicin cytotoxicity by chlorpromazine in doxorubicin resistant mouse P388 leukemia cells]. AB - The intracellular uptake, retention and cytotoxicity of pirarubicin, an anthracycline derivative, combined with chlorpromazine were investigated in doxorubicin-resistant mouse P388 leukemia (P388/DXR) cells. The number of viable cells was determined by the dye exclusion method. Chlorpromazine increased the cytotoxicity of pirarubicin in a dose-related manner in P388/DXR cells. A similar dose-response relationship was observed for chlorpromazine in increasing net intracellular pirarubicin accumulation. The accumulation was based on block of enhanced pirarubicin efflux from resistant cells by chlorpromazine. However, chlorpromazine did not affect cytotoxicity or transport of pirarubicin in the drug-sensitive cell line. The possible mechanisms of the restoration of pirarubicin sensitivity in P388/DXR cells by chlorpromazine are discussed. PMID- 2262881 TI - [Protective activities of a Chinese medicine, hochu-ekki-to, to impairment of hematopoietic organs and to microbial infection]. AB - Effect of Hochu-ekki-to (HET) on the number of peripheral leukocytes (PL) and their functions in cyclophosphamide (CY)-treated or gamma ray-irradiated mice was investigated. By treatment of mice with anticancer agent CY or gamma ray irradiation, unfavorable side effects usually occurred to impair hematopoietic organs, causing bone marrow disorder. However, it was significantly protected by oral administration of HET (1 g/kg/d) to CY-treated or gamma ray-irradiated mice. The numbers of neutrophils and monocytes in PL were restored to the normal level, and colony-stimulating factor (CSF) was induced in the sera of mice by HET in a dose-dependent manner. The induction of serum CSF reached a peak at 3h after HET administration. Colony-forming unit of bone marrow cells in the spleen adoptively transferred into syngeneic mice, that is defined as CFU-S, was extremely reduced by CY-treatment. However, when HET was orally administered, CFU-S of CY-treated mice was markedly stimulated, suggesting that bone marrow cells were reactivated for further proliferation and mobilization. HET enhanced other leukocyte functions in CY-treated mice; i.e., superoxide production of neutrophils and phagocytic activity of macrophages. Thus, oral administration of HET to CY treated mice enforced protection against Pseudomonas aeruginosa infection. PMID- 2262882 TI - [Protective effects of antioxidants on experimental liver injuries]. AB - Protective effects of 14 kinds of antioxidant on liver injury induced by carbon tetrachloride (CCl4) were investigated in terms of serum enzyme activities and bilirubin concentration. Consequently, the significant protective effects were found in sesamol, ellagic acid, cysteamine and cysteine. These antioxidants clearly decreased the lipid peroxide in the liver tissue. The protective effects on CCl4-induced liver injury in vivo were independent of the inhibitory activities on lipid peroxidation in hepatic mitochondria fraction in vitro. PMID- 2262883 TI - Carotenoid functions in photoprotection and cancer prevention. AB - Carotenoid pigments in in vitro and in vivo systems are able to quench excited species, such as singlet oxygen and free radicals. The U.S. Food and Drug Administration has approved beta-carotene for use in humans for prevention of the photosensitivity associated with the orphan disease, erythropoietic protoporphyria. Although the usual adult dose used is 180 mg/day, intake up to 300 mg/day is allowed. No serious toxicity to beta-carotene has been reported. Carotenoids have demonstrated some anticancer activity in certain animals. Clinical trials in populations at high risk for developing certain types of cancer are presently underway, using doses of beta-carotene ranging from 15 to 50 mg/day, or much lower doses than used for photosensitivity prevention. There is no way of predicting which dose will be effective in preventing cancer: The lower doses were chosen to avoid development of marked carotenodermia; they are sufficient to cause an increase in the serum carotenoid level but may, occasionally, in individuals, cause the development of some degree of carotenodermia. This article reviews development of the use of beta-carotene for preventing photosensitivity in humans, studies investigating the anticancer properties of the carotenoids, and studies aimed at understanding how the carotenoids exert their protective functions. PMID- 2262884 TI - Time and dose-response study of the effects of vanadate in rats: changes in blood cells, serum enzymes, protein, cholesterol, glucose, calcium, and inorganic phosphate. AB - A daily dosage of vanadate (0.9 mgV/kg) injected subcutaneously for 16 days to adult rats produced significant changes in blood cells and serum elements. The hematological changes included an increase in white blood cell count at two days after the last injection. At five days, red blood cell count (RBC), hemoglobin, and packed cell volume (PCV) were low. At 12 days, there were reductions in RBC, hemoglobin, PCV, and lymphocyte counts and an increase in polymorphonuclear cell (PMN) counts. At 25 days, RBC, hemoglobin, and PCV were still low. At 40 days, the only change was a reduction in RBC. Changes in the serum at two days posttreatment were a reduction in lactic dehydrogenase activity (LDH), alkaline phosphatase activity (AP), calcium, albumin, and total protein and an increase in cholesterol. At five days, glutamic-oxalacetic transaminase (GOT), lactic dehydrogenase (LDH), inorganic phosphate, and total protein were low and calcium was high. At 12 days, GOT, glutamic-pyruvic transaminase (GPT), and LDH were reduced, and the levels of calcium and cholesterol were elevated. At 25 days, there was a reduction in GPT and LDH and an increase in glucose, calcium, and albumin. At 40 days, the levels of GOT, LDH, AP, and inorganic phosphate were still low. Vanadate at lower dosage levels (0.3-0.6 mg V/kg per day for 16 days) also produced significant changes in blood cellular and serum elements but at lesser degrees of severity. These findings show that the exposure of rats repeatedly to low levels of Vanadate caused anemia, elevation in blood cholesterol levels, and a reduction in serum enzymes activities. PMID- 2262885 TI - Cancer of the rectum in relation to components of the Spanish diet. AB - Cancer of the rectum is common in most industrialized countries. It is considered to be the result of a combination of environmental (diet, tobacco, alcohol, etc.) and genetic factors. We studied the evolution of morbidity and mortality due to cancer of the rectum and sigmoid in Spanish provinces and its relationship to different Spanish diet components. Our study covered the period 1977-1985. We used the indirect method to determine morbidity and mortality rates per 100,000 population, grouped according to age and sex. The consumption of different diet components was obtained from National Statistics Institute publications on the subject. These components were total lipids, animal fats, vegetable fats, butter and pork lard, margarine, fiber, and alcohol (all in g/person/day). For the study period, the mean national standardized mortality was 5.26 per 100,000 population and morbidity was 171.57 per 100,000. Provinces having rates above and below the national average were noted. The study revealed that, overall, alcohol consumption presents a 0.42 (p less than .001) positive correlation with standardized mortality, as does total lipid consumption. PMID- 2262886 TI - The relationship between inhalation of nitrogen dioxide, the immune system, and progression of a spontaneously occurring lymphoma in AKR mice. AB - The effects of exposure to an ambient level of nitrogen dioxide (NO2) on the development and progression of the spontaneous T-cell lymphoma in AKR/cum mice are evaluated. The animals were exposed to 0.25 ppm +/- 0.05 ppm NO2 for 7 hr/day, 5 days/week for up to 181 days. Following exposure periods of 37, 71, 111, 141, and 181 days, the extent of lymphoma was determined microscopically in histologic sections of the thymus, spleen, lymph nodes, lung, and liver. In addition, T-lymphocyte subpopulations were quantitated by flow cytometry. The results indicate that the development and progression of lymphoma in mice was influenced by intermittent inhalation of NO2. The lymphoma was detectable earlier in control animals and the survival of the NO2-exposed group was significantly higher. The T-lymphocyte subpopulations were significantly lower in NO2-exposed animals following 37 and 181 days of NO2 exposure. The T-helper/inducer (CD4+) lymphocytes were adversely affected to the greatest extent, explaining in part the more aggressive behavior of the lymphoma in the control animals. Most importantly, these studies provide additional evidence that in vivo exposure to a level of NO2 commonly encountered in polluted metropolitan areas adversely affects cells of the immune system. In the case of the AKR mouse, the adverse effect of NO2 on CD4+ cells manifested itself by retarding development and progression of the spontaneous lymphoma. Our data suggest that this neoplasm may be dependent on growth factors such as interleukin 2, produced by CD4+ lymphocytes in the early stages. PMID- 2262887 TI - Pharmacologic manipulation of the murine pulmonary biochemical response to NO2. AB - The possible sources of biochemical changes in the lung, including changes in activities of lactate dehydrogenase (LDH), beta-glucuronidase (beta-GLU), choline kinase (CHK), and protease inhibitor (PI), as well as protein content, were evaluated following exposure to NO2. Hydroxyurea-induced granulocytopenia attenuated the LDH and beta-GLU responses (46% and 61%, respectively) following acute, but not subacute, exposure to NO2. Increases in PI activity and pulmonary protein content following exposure to NO2 were not altered by inhibition of protein synthesis by cycloheximide. The observed increase in PI activity appears to result from an activation process, whereas a major source of increased pulmonary protein content following exposure appears to occur from leakage into the lung. The response of the lung to irritant insult is thus dynamic, and the contribution from various sources to the biochemical makeup of the lung following irritant insult may depend on the phase of the pulmonary response. PMID- 2262888 TI - Trends in malignant skin melanoma and other skin cancers in Spain, 1975-1983, and their relation to solar radiation intensity. AB - Epidemiological studies have shown solar exposure to play an important role in the appearance of skin cancer. We investigated the association between mortality standardized by the indirect method for malignant skin melanoma and other skin cancers and the mean intensity of solar radiation during July and August for the different provinces in Spain. A statistically significant relation was observed (p less than .05) for these two months but not upon considering mean annual solar radiation. We thus suggest that intermittent, intense exposure to sunlight constitutes an important risk factor for skin cancer. We observed an 8.5% and 15.72% increase in mortality due to malignant skin melanoma and other skin cancers, respectively, during the period 1975-1983. Mortality was slightly higher among males than females. PMID- 2262889 TI - Detoxification of patulin by adduct formation with cysteine. AB - Patulin adduct was formed by reacting equimolar amounts of patulin and cysteine at pH 6.0. The bactericidal effect of the adduct mixture was less than one hundredth of that of free patulin in plate and liquid cultivation tests with Escherichia coli W 3110 thy pol A1 and pol A1+ strains. The bacterial strains did not liberate free patulin from the adduct mixture present in the growth medium. Neither patulin nor the adduct mixture induced repair effects in E. coli. The oral LD50 of patulin for NMRI male mice was 29 mg/kg. For the adduct mixture, not even as high a dose as 2,370 mg patulin equivalents per kg body weight caused any deaths or macroscopic pathological alteration. Neither patulin nor the adduct mixture was mutagenic to the histidine auxotroph Salmonella typhimurium strains TA 100 and TA 98 in microsomal activation tests or to TA 1950 and 1951 in host mediated assay. PMID- 2262890 TI - Selective vasopressin inhibition in rats with heart failure decreases afterload and results in venodilatation. AB - The hemodynamic effects of selective inhibition of arginine vasopressin (AVP) with a V1 antagonist, (CH2)5yreAVPa CL-1-4A, were studied in normal rats (n = 17) and in rats 4 weeks after coronary artery ligation with large myocardial infarctions and elevated left ventricular end-diastolic pressures (n = 22). In normal rats AVP inhibition with a 35-micrograms/kg bolus of AVP V1 antagonist did not change heart rate, right atrial, left ventricular systolic, left ventricular end-diastolic or aortic pressures. There were also no changes in mean circulatory filling pressure, unstressed vascular volume, blood volume or venous compliance. In rats with infarction and elevated left ventricular end-diastolic pressures, AVP inhibition did not change heart rate, right atrial pressure, mean circulatory filling pressure or blood volume, but mean aortic pressure decreased from 103 +/- 3 to 88 +/- 2 mm Hg (P less than .001), venous compliance increased (P less than .001) from 2.17 +/- 0.07 to 3.04 +/- 0.11 ml/mm Hg/kg and unstressed vascular volume decreased from 42.3 +/- 3.1 to 34.7 +/- 2.6 ml/kg (P less than .05). We conclude that inhibition of AVP with a specific V1 antagonist had no effect on the venous or arterial circulations in normal rats, but in rats with left ventricular dysfunction and heart failure after chronic myocardial infarction, AVP inhibition decreased arterial pressure and caused venodilatation. PMID- 2262891 TI - Bupivacaine inhibits the transient outward K+ current but not the inward rectifier in rat ventricular myocytes. AB - The effects of bupivacaine on K+ currents in isolated rat ventricular myocytes were examined using the whole-cell patch-clamp technique. Bupivacaine at concentrations greater than 3 microM produced both a reduction in the peak current amplitude and a marked increase in the rate of inactivation of the transient outward current (Ito). Examination of its time course showed that there was no inhibition before the beginning of a depolarizing pulse. However, upon continuous depolarization (i.e., during channel opening) inhibition of Ito developed in an exponential manner, the rate and magnitude of which were dependent on bupivacaine concentration. The IC50 for inhibition of Ito was 22 microM. Bupivacaine had no effect on the voltage-dependence of steady-state inactivation or the rate of recovery from inactivation. The (+)- and (-) stereoisomers of bupivacaine were equipotent indicating that there is no stereoselectivity to the inhibition of Ito. Increasing the hydrophobicity of the tertiary amine on bupivacaine greatly enhanced its potency. Thus, octylacaine (1 octyl-2',6'-pipecoloxylidide) (C8-N) was 6 times more potent than bupivacaine (C4 N) and 200 times more potent than mepivacaine (C1-N). In contrast to their effects on Ito, bupivacaine (1 mM) and octylacaine (100 microM) failed to produce any block of the inward rectifier K+ current. However, mepivacaine (3 mM) reduced inward rectifier K+ current reversibly by approximately 50%. These results suggest that inhibition of Ito may contribute to bupivacaine-induced cardiotoxicity. PMID- 2262892 TI - The involvement of central noradrenergic systems and corticotropin-releasing factor in defensive-withdrawal behavior in rats. AB - The role of the central noradrenergic systems and corticotropin-releasing factor (CRF) in modulating defensive withdrawal behavior was studied in rats. The apparatus consisted of a small chamber set on one side of a one-meter open field, into which the rat was placed to start the test. When rats were unfamiliar with the apparatus, they displayed species typical defensive withdrawal behavior with long latencies to emerge from and a high proportion of time spent in the small chamber. Intraperitoneal administration of clonidine (0.03 mg/kg), l-propranolol (2.5 micrograms/kg), prazosin (0.1 mg/kg) or chlordiazepoxide (CDP, 5 mg/kg) each significantly decreased the latency to emerge from and the mean time spent in the small chamber (MTIC) and increased the number of chamber entries. When rats were familiar with the apparatus, prior restraint for 20 min significantly increased the latency and MTIC, and decreased the number of chamber entries and rears, but did not alter locomotor activity. Prazosin, clonidine, CDP, l-propranolol and the CRF-antagonist, alpha-helical CRF9-41 (25 micrograms i.c.v.), reversed the restraint-induced increase in the latency and MTIC. CRF (10-100 ng i.c.v.) dose dependently induced defensive withdrawal behavior in rats familiar with the apparatus; the minimum statistically significant dose was 50 ng. dl-Propranolol (5 mg/kg) and CDP blocked the CRF-induced changes in the latency to emerge and the MTIC; whereas clonidine and prazosin significantly reduced the latency, but had no statistically significant effects on the MTIC. Phenylephrine (25-200 ng i.c.v.) dose-dependently induced defensive withdrawal behavior. This effect of phenylephrine (200 ng) was significantly antagonized by prazosin or alpha-helical CRF9-41 (25 or 50 mg i.c.v.), but not by CDP. Our results suggest that the hyperactivity of the central noradrenergic systems caused by exposure to the novel environment may stimulate the release of CRF, which through some unknown mechanism induces defensive withdrawal behavior in rats. Activation of beta adrenergic receptors may also induce defensive withdrawal. PMID- 2262893 TI - Interactions between scopolamine and muscarinic cholinergic agonists or cholinesterase inhibitors on spatial alternation performance in rats. AB - The effects on working memory of the muscarinic cholinergic agonists oxotremorine, arecoline, RS86 and pilocarpine, and the cholinesterase inhibitors physostigmine and tetrahydroaminoacadine were investigated in male F344 rats. Working memory was assessed by behavior maintained under a spatial alternation schedule of food presentation in which the interval between trials was varied from 2 to 32 sec. Under control conditions the percentage of correct responses decreased as the retention interval was varied from 2 to 32 sec. Administered alone the cholinergic agonists oxotremorine (0.01-0.1 mg/kg), arecoline (3-30 mg/kg), RS86 (0.3-3 mg/kg) and pilocarpine (0.3-3.0 mg/kg), and the cholinesterase inhibitors physostigmine (0.01-0.1 mg/kg) and tetrahydroaminoacridine (0.3-3.0 mg/kg) either had no effect on or produced dose related deficits in working memory and decreases in response rates. The muscarinic antagonist scopolamine (0.1 mg/kg) produced retention interval dependent decreases in the percentage of correct responding and rates of responding. The cholinergic agonists and tetrahydroaminoacridine failed to reverse the effects of scopolamine. However, physostigmine produced a dose dependent reversal of the working-memory deficits and response-rate decreasing effects of scopolamine. The present results are consistent with the interpretation that drugs which primarily enhance M2 muscarinic cholinergic transmission are ineffective in enhancing working memory or in reversing scopolamine-induced deficits in working memory. PMID- 2262894 TI - In vivo measurement of noradrenaline and 3,4-dihydroxyphenylethyleneglycol in the rat hypothalamus by microdialysis: effects of various drugs affecting noradrenaline metabolism. AB - The extracellular concentrations of noradrenaline (NA) and 3,4 dihydroxyphenylethyleneglycol (DOPEG), one of the major metabolites of brain NA, in the hypothalamus of urethane-anesthetized rats were monitored by in vivo microdialysis followed by a sensitive and simultaneous determination of the two substances using high-performance liquid chromatography with electrochemical detection. The effects of various drugs that affect central NA metabolism were also examined. Resting levels of NA and DOPEG were constant during 1 and 6 hr after the start of perfusion, the mean values being 3.8 +/- 0.4 pg/30 min for NA and 107.5 +/- 9.1 pg/30 min for DOPEG (mean +/- S.E.M. of 7 animals). Tetrodotoxin (1 microM), when added to the perfusion medium, reduced the output of NA below the detection limit (0.5 pg) and also decreased the DOPEG output by 60%. Clonidine (0.2 mg/kg i.p.) caused a marked reduction in both the NA and DOPEG outputs, whereas yohimbine (5 mg/kg i.p.) significantly increased both the NA and DOPEG outputs. Desipramine (2 and 5 mg/kg i.p.) produced a dose-dependent increase in the NA output, although it caused a gradual decline of the DOPEG output. The atypical antidepressant mianserin (2 and 5 mg/kg i.p.), which possesses both alpha-2 antagonist and weak NA uptake inhibitory actions, produced a less marked increase in the NA output with no or only a small decrease in the DOPEG output. Therefore, it is suggested that monitoring the extracellular concentrations of both NA and DOPEG enables the discrimination between the action of drugs inhibiting the NA uptake and that of drugs enhancing the NA release, and that this method is useful to obtain detailed information about central NA metabolism in vivo. PMID- 2262895 TI - An isobolographic analysis of the antinociceptive effect of systemically and intrathecally administered combinations of clonidine and opiates. AB - The antinociceptive interaction of opiate analgesics with clonidine was examined with the tail-flick and 55 degrees C hot plate tests. Male Sprague-Dawley rats received fixed ratios of clonidine to fentanyl, meperidine or morphine by i.v. and intrathecal injection. Data are expressed as percentage of maximal possible effect and the dose producing 50 percentage of maximal possible effect for each drug or drug combination is used to index potency. The rank order of potency in both tests after i.v. administration is fentanyl much greater than clonidine greater than meperidine greater than or equal to morphine and after intrathecal administration it is morphine greater than fentanyl much greater than clonidine much greater than meperidine. Isobolographic analysis shows that the effect of clonidine combined with an opiate is additive after i.v. administration; the exception is that morphine and clonidine are synergistic in the hot plate test. The intrathecal combinations of clonidine with morphine or meperidine produces a supra-additive antinociceptive effect in the tail-flick test but not in the hot plate test. Fentanyl does so in both tests. These data confirm a positive interaction between clonidine and opiates in producing antinociception. This interaction may be additive or synergistic, depending on route of administration and the nociceptive test used. The timing of injections and pharmacokinetic factors may also influence the results. Moreover, these results suggest that the interaction between the opiate and alpha-2 adrenergic receptors occurs within the spinal cord. PMID- 2262896 TI - Low-dose caffeine physical dependence in humans. AB - This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized. PMID- 2262897 TI - Comparison of central nervous system and peripheral pharmacodynamics to atropine pharmacokinetics. AB - Two experiments were designed to examine the pharmacokinetic-pharmacodynamic relationship for the central nervous system and peripheral effects of atropine. According to a random Latin square design, healthy young male volunteers were given i.m. injections containing single doses of placebo or 0.5, 1.0, 2.0 or 4.0 mg of atropine. The central nervous system tests included wheel tracking, a coordination task, and digit symbol substitution, a memory-psychomotor speed task; the physiological variable was heart rate. The pharmacokinetics of atropine were best described by a two-compartment model with very rapid first order absorption. Changes in plasma atropine levels and heart rate closely overlapped for all four doses throughout most of the time course. In contrast, the differential time course of changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effects of atropine. Alternative explanations are discussed, including differential atropine effects on peripheral M2 receptors mediating a heart rate effect and on CNS M1 receptors mediating the memory psychomotor effect. PMID- 2262898 TI - Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain. AB - The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding [3H]N-methylscopolamine by pirenzepine and AF-DX 116 (11[[2 [(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3 b][1,4]benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of [3H]N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of [3H]quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities. Treatment of homogenates of the cerebral cortex with benzilylcholine mustard caused a selective loss of the majority of the [3H]N-methylscopolamine binding sites but spared 25% of the sites labeled by [3H]quinuclidinyl benzilate The results of pirenzepine/[3H]quinuclinyl benzilate competitive binding experiments on cerebral cortex treated with benzilylcholine mustard showed that the residual binding sites for [3H] quinuclidinyl benzilate were enriched in M1 muscarinic receptors. PMID- 2262899 TI - The cholecystokinin receptor antagonist devazepide enhances morphine-induced analgesia but not morphine-induced respiratory depression in the squirrel monkey. AB - The effects of the cholecystokinin antagonist devazepide on analgesia and respiratory depression induced by morphine in squirrel monkeys were examined. Pain thresholds were determined using the tail withdrawal procedure, in which monkeys restrained in chairs kept their tails in cool (35 degrees C) water for at least 20 sec, but withdrew them from warm (55 degrees C) water in less than 4 sec. Morphine produced a dose-related increase in tail withdrawal latencies from warm water. Devazepide (injected i.p. or p.o.) had no effect on tail withdrawal latencies when given alone but enhanced the analgesic effects of morphine. The devazepide dose-response curve for morphine enhancement was bell-shaped with doses of 3, 10, 30 and 100 micrograms/kg injected i.p. increasing morphine analgesia whereas higher and lower dose did not. In a separate group of monkeys, morphine produced dose-dependent decreases in respiratory rate and oxygen tension and increases in carbon dioxide tension. In contrast to its effects on morphine analgesia, devazepide had no effect on the various indices of morphine-induced respiratory depression. These data suggest that devazepide may have therapeutic utility as an adjuvant to morphine analgesia allowing lower dose of the opiate to be used to relieve pain and reducing the risk of opiate-induced respiratory depression. PMID- 2262900 TI - Ontogeny of fetal renal organic cation excretion: a study with cimetidine and ranitidine during the latter half of gestation in the pregnant ewe. AB - The organic cation cimetidine undergoes renal tubular secretion in the near-term ovine fetus. We investigated the ontogeny of renal tubular secretion of organic cations in the fetus from 80 days of gestation (term = 145). Sixteen sheep were administered both cimetidine and ranitidine in random order by a combination of bolus and i.v. infusion to achieve steady-state plasma concentrations of 1000 to 2000 ng/ml. A further two sheep received cimetidine only. Steady-state plasma concentrations were reached within 2 to 3 hr. Creatinine was used as a marker of glomerular filtration rate. Maternal renal clearance of cimetidine (0.51 +/- 0.18 l/min) and ranitidine (0.54 +/- 0.14 l/min) were not correlated with the period of gestation. Cimetidine/creatinine and ranitidine/creatinine renal clearance ratios were higher than unity being 5.48 +/- 1.91 and 5.65 +/- 1.18, respectively. Fetal creatinine renal clearance increased exponentially with gestational age (r2 = 0.577, P less than .001). Fetal renal clearance of both cimetidine and ranitidine also increased exponentially with gestational age, this trend being more clear-cut for cimetidine (r2 = 0.582, P less than .001) than for ranitidine (r2 = 0.254, P = .046). The rates of increase for cimetidine and ranitidine were similar to that for creatinine (P greater than .05). At 80 days, cimetidine/creatinine and ranitidine/creatinine renal clearance ratios (3.0 and 4.4, respectively) were higher than unity and did not increase further during the remainder of gestation. Therefore, the ovine fetus possesses an efficient tubular secretory pathway for organic cations by 80 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262901 TI - Reversal of intracellular toxicity of the trichothecene mycotoxin T-2 with monoclonal antibody. AB - The trichothecene mycotoxin T-2 is a potent inhibitor of intracellular protein synthesis. We have previously shown that a mouse immunoglobulin G1 monoclonal antibody (15H6) specific for T-2 toxin can neutralize the in vitro protein synthesis inhibitory effect of the toxin in human B-lymphoblastoid cultures, and protect rats from lethal toxemia. We now report that these monoclonal antibodies can induce the net efflux of [3H]-T-2 toxin from poisoned human B-lymphoblastoid cells in vitro, and restore protein synthesis. Administration of the monoclonal antibodies (250 mg/kg) 30 min before infusion of a lethal dose (1 mg/kg) of T-2 toxin causes the sequestration of the toxin in the plasma compartment. When administered 35 min after T-2 toxin, a time when the bulk of toxin is in the tissues, the monoclonal antibodies facilitate the migration of toxin back into the plasma compartment. These data demonstrate that monoclonal antibodies can be of therapeutic value against an intracellular toxin. PMID- 2262902 TI - Central adenosinergic system involvement in ethanol-induced motor incoordination in mice. AB - To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol (i.p.)-induced motor incoordination was evaluated by rotorod. Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p. Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions. Results from R PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs. S-diastereoisomer, suggesting predominance of adenosine A1 subtype. However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2. No effect of ethanol on blood or brain levels of [3H]R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol. There was no escape of i.c.v.-administered [3H]R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262903 TI - Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C. AB - UCN-01 is a staurosporine-related compound that was isolated from the culture broth of Streptomyces sp. and shows potent and selective inhibitory activity against protein kinase C. Cellular inhibitory activity of UCN-01 against protein kinase C and cytotoxicity of UCN-01 were compared with those of staurosporine. When the mechanism of inhibitory activity was investigated in vitro, UCN-01 as well as staurosporine inhibited the activity of the catalytic domain of protein kinase C. In spite of direct inhibition against the catalytic domain of protein kinase C, cytotoxicity of UCN-01 was much lower than that of staurosporine. In addition, UCN-01 showed more selective inhibitory activity against protein kinase C than did staurosporine because of the sole structural difference at C-7. Therefore, a series of 7-O-alkyl derivatives of UCN-01 was synthesized and investigated. Interestingly, one of the compounds, the beta-methoxy derivative, showed 3-fold greater potency and 17-fold more selective inhibitory activity against protein kinase C than did UCN-01. PMID- 2262904 TI - Zolpidem and triazolam in humans: behavioral and subjective effects and abuse liability. AB - Zolpidem, which is currently marketed in Europe as a hypnotic, is a short duration imidazopyridine whose actions are mediated at the gamma-aminobutyric acid benzodiazepine receptor complex. However, zolpidem produces a variety of biochemical differences from classic benzodiazepine agonists including showing selectivity for the central BZ1 (omega 1) receptor subtype as well as showing a different pattern of distribution of binding sites. This study compared zolpidem to the benzodiazepine hypnotic triazolam in 15 healthy male volunteers with histories of sedative drug abuse. Placebo, zolpidem (15, 30 and 45 mg) and triazolam (0.25, 0.5 and 0.75 mg) were administered p.o. in a mixed sequence in a double-blind, cross-over design. The onset time with zolpidem was faster than with triazolam, with peak effects of both drugs occurring at 1 to 2 hr after administration. Both zolpidem and triazolam produced dose-related decrements in performance on various performance tasks including circular lights, reaction time, balance, number recall and the digit symbol substitution test. Both drugs also produced similar dose-related changes on various observer ratings including overall strength of drug effect. Triazolam, but not zolpidem, increased subject- and observer-rated sleepiness and produced greater impairment on a picture memory task. Zolpidem, but not triazolam, produced increases in subject ratings of various somatic symptoms (e.g., dizzy, anxious and queasy) and there were 9 days on which subjects vomited after zolpidem, but none after triazolam. Although the highest dose of both drugs was identified by subjects as being active, the highest dose of triazolam was identified as being barbiturate, benzodiazepine or alcohol, almost twice as often as the highest dose of zolpidem. Overall, this study shows that although zolpidem produces many effects in common with triazolam, it also has a unique profile of effects distinguishable from classic benzodiazepine agonists. The mechanism(s) underlying these differences is unclear, but may be related to the atypical biochemical profile of zolpidem. PMID- 2262905 TI - Interactions between N-methyl-D-aspartate and CGS 19755 administered intramuscularly and intracerebroventricularly in pigeons. AB - Behavioral effects of N-methyl-D-aspartate (NMDA) and the competitive NMDA antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) were studied in pigeons. NMDA decreased responding under a fixed-ratio schedule of food presentation and was 8000 times more potent administered intracerebroventricularly (i.c.v.) as compared to intramuscularly (i.m.). CGS 19755 was 870 times more potent in producing catalepsy when administered i.c.v.; however, the duration of catalepsy was similar by the two routes of administration. Administered i.m. CGS 19755 decreased response rates only at doses that also produced catalepsy; administered i.c.v. some doses of CGS 19755 decreased responding without producing other behavioral effects. Rate-decreasing effects of i.m. NMDA were attenuated by i.m. CGS 19755; however, when CGS 19755 was administered i.c.v., there was little or no antagonism of NMDA. Rate decreasing effects of i.c.v. NMDA were not attenuated by i.m. or i.c.v. CGS 19755 up to doses that produced catalepsy or eliminated responding. The large difference in potency between i.m. and i.c.v. administration for NMDA and for CGS 19755, as well as the slower onset of catalepsy when CGS 19755 was administered i.m., suggests these compounds do not readily cross the blood-brain barrier when administered parenterally. The inability of CGS 19755 to attenuate the rate decreasing effects of NMDA when CGS 19755 or NMDA was administered i.c.v. suggests NMDA might decrease responding by different mechanisms when administered i.m. or i.c.v. in pigeons. Together these results indicate antagonism of NMDA in this study, and perhaps in other studies, when both NMDA and CGS 19755 were administered parenterally, might result from a peripherally mediated interaction. Moreover, this agonist-antagonist interaction is not a simple, competitive antagonism. PMID- 2262906 TI - A new, highly selective CCK-B receptor radioligand ([3H][N-methyl-Nle28,31]CCK26 33): evidence for CCK-B receptor heterogeneity. AB - [N-methyl-Nle28,31]CCK26-33 (SNF 8702) is a nonsulfated cholecystokinin octapeptide analog that is highly selective for cholecystokinin-B (CCK-B) receptors. Inhibition studies using [125I] Bolton-Hunter-labeled CCK-8 show that SNF 8702 has over 4,000-fold greater affinity for CCK receptors in guinea pig cortex relative to those in guinea pig pancreas. SNF 8702 was tritium-labeled to a specific activity of 23.7 Ci/mmol and its binding properties characterized for guinea pig brain membrane preparations. [3H]SNF 8702 binds to a single site with high affinity (Kd = 0.69-0.90 nM) in guinea pig cortex, cerebellum, hippocampus and pons-medulla. Of these four tissues, the highest receptor density was measured in the cortex (86 fmol/mg of protein) and the lowest in the pons-medulla (22 fmol/mg of protein). In contrast to findings of single-site binding in some brain regions, evidence for CCK-B receptor heterogeneity is observed under other conditions. [3H]SNF 8702 binding to membranes prepared from whole guinea pig brain shows biphasic association kinetics at a concentration of 2.0 nM consistent with the presence of binding site heterogeneity. Binding site heterogeneity is consistently observed for [3H]SNF 8702 binding to guinea pig whole brain membranes in saturation studies where a high-affinity site (Kd = 0.31 nM) is distinguished from a low-affinity site (Kd = 3.3 nM). Binding site heterogeneity is also observed for the midbrain-thalamic region. CCK-B receptor heterogeneity is suggested by the effect of the guanyl nucleotide analogue, guanylyl imidodiphosphate (Gpp(NH)p), on [3H]SNF 8702 binding to CCK-B receptors in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262907 TI - Chronic cocaine treatment enhances the responsiveness of the left anterior descending coronary artery and the femoral artery to vasoactive substances. AB - The mechanism by which cocaine produces sudden cardiac death has not been elucidated, but clinical evidence indicates that it may be due to a direct or indirect action on coronary vessels. The present study was designed to compare the responses of the isolated left anterior descending (LAD) coronary artery and femoral artery taken from untreated dogs with the response of these vessels taken from dogs administered cocaine (1 mg/kg i.v.) daily for 4 weeks. The actions of norepinephrine, U-46619 (a thromboxane A2 analog) and serotonin (5-HT) were evaluated. The direct vascular action of cocaine was also determined. Morphology of the blood vessels was evaluated by scanning electron microscopy. Chronic cocaine treatment significantly increased the sensitivity and maximum response of the femoral artery to norepinephrine, U-46619 and 5-HT. The sensitivity of the LAD coronary artery to U-46619 and 5-HT and the maximum response to U-46619 and 5 HT were also enhanced. Vasoconstriction produced by cocaine was not dose dependent and only occurred at high concentrations (10(-5)-10(-4) M). Morphology of the vessels was evaluated by scanning electron microscopy. Femoral arteries from cocaine-treated dogs exhibited loss of endothelial integrity, areas of excessive endothelial cell sloughing and thrombus formation. LAD coronary arteries exhibited only areas of enhanced endothelial cell sloughing. The results of this study indicate that the femoral artery and the LAD coronary artery are more sensitive to endogenous vasoactive substances after chronic cocaine use, which may result in enhanced peripheral vasoconstriction and cardiac ischemia. Morphological results demonstrate femoral arterial thrombosis associated with cocaine use. PMID- 2262908 TI - Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s. AB - The metabolism of lidocaine by human hepatic microsomes and purified human cytochrome P-450s, P-450NF (P450IIIA4), P-450MP (a P450IIC form) and P-450PA (P450IA2) was examined and their metabolism was compared with that by rat hepatic cytochrome P-450s. Human hepatic microsomes produced monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-LID) from lidocaine. In a reconstituted system with dilauroylphosphatidylcholine, P-450NF efficiently produced MEGX. P 450PA was not efficient in lidocaine N-deethylation (formation of MEGX) but produced 3-OH-LID. P-450NF and P-450MP did not produce 3-OH-LID. Lidocaine N deethylation activity of P-450NF was enhanced in a modified reconstituted system with a phospholipid mixture and sodium cholate. P-450NF appears to be an ortholog to rat P450 PB-1 (P450IIIA2). Anti-P450 PB-1 antibody cross-reacted with P-450NF and efficiently inhibited lidocaine N-deethylation in human hepatic microsomes. The correlation of lidocaine N-deethylation activity with the concentration of P 450NF determined immunochemically with anti-P450 PB-1 antibody was good (r = 0.81). In addition, correlation between P-450NF content estimated with anti-P450 PB-1 and anti-P-450NF preparations was good (r = 0.96). These results suggest that rat P450 PB-1 and human P-450NF have closely related properties and P-450NF is the major enzyme involved in lidocaine N-deethylation in human hepatic microsomes. PMID- 2262909 TI - Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress induced tachycardia: a study using microdialysis. AB - Previous studies involving local microinjection of drugs that interfere with gamma-aminobutyric acid (GABA)A receptor-mediated synaptic inhibition have led to the suggestion that endogenous GABA suppresses the activity of a sympatho excitatory mechanism in the dorsomedial hypothalamus in rats. In this study, microdialysis was used to assess and to alter pharmacologically extracellular levels of GABA within this region while simultaneously monitoring heart rate and blood pressure. In anesthetized rats, local microdialysis for 15 min with 2.5, 10 and 40 mM nipecotic acid, an inhibitor of GABA uptake, caused concentration related increases in GABA and taurine in the extracellular space, but no significant change in heart rate or arterial pressure. Similar perfusion with 37.5, 75 and 150 mM KCl caused concentration-related increases in GABA as well as aspartate, glutamate, taurine, glycine and alanine. Only modest, variable increases in heart rate and no effect on arterial pressure were observed during the perfusions with high potassium. In conscious rats, unilateral microdialysis of the dorsomedial hypothalamus with 0.5 mM nipecotic acid for 2 to 2.5 hr before stress coupled with contralateral microinjection of muscimol (88 pmol/250 nl) 5 min before stress significantly reduced air stress-induced tachycardia; this reduction in tachycardia was associated with markedly elevated levels of GABA in dialysates collected from the dorsomedial hypothalamus. Neither treatment alone significantly influenced stress-induced increases in heart rate, although perfusion with nipecotic acid alone evoked similar elevations in extracellular GABA. These results suggest that extracellular levels of endogenous GABA in the dorsomedial hypothalamus may regulate the cardiovascular response to stress. PMID- 2262910 TI - Biphasic modulation of acetaminophen bioactivation and hepatotoxicity by pretreatment with the interferon inducer polyinosinic-polycytidylic acid. AB - Interferons and interferon induction can inhibit cytochromes P-450 and reduce the bioactivation and hepatotoxicity of acetaminophen. However, since P-450 inhibition often is followed by P-450 induction, which would enhance acetaminophen hepatotoxicity, the possibility of a biphasic modulation of acetaminophen hepatotoxicity by interferons was investigated. Outbred male CD-1 mice of various ages, and young inbred male C57BL/6 mice were given the interferon inducer, polyinosinic-polycytidylic acid (Poly I-C), 10 mg/kg intraperitoneally, followed 1 to 48 days later by a single dose of acetaminophen, 300 to 450 mg/kg intraperitoneally. Hepatotoxicity was assessed by the peak plasma concentration of alanine aminotransferase (ALT) occurring between 0 and 48 hr after acetaminophen treatment. Poly I-C inhibited the hepatotoxicity of acetaminophen given within 8 days, with maximal inhibition between 1 and 4 days. Conversely, a maximal 7-fold enhancement of ALT concentration was observed in CD 1 mice when 300 mg/kg of acetaminophen was given 32 days after Poly I-C (P less than 0.05). In the C57BL/6 strain, Poly I-C inhibited the hepatotoxicity of acetaminophen when given within 16 days, whereas a maximal 20-fold enhancement of ALT concentration was observed when 300 mg/kg of acetaminophen was given 24 days after Poly I-C (P less than 0.05). The mechanism of toxicologic enhancement was examined in male C57BL/6 mice using the same treatment regimen. Biochemical assessment of hepatotoxicity was confirmed by detailed histologic evaluation. Plasma concentrations of acetaminophen and metabolites were determined by high performance liquid chromatography. Acetaminophen bioactivation was quantified by production of the glutathione-derived cysteine and mercapturic acid conjugates of acetaminophen. Poly I-C pretreatment produced a 5-fold increase in acetaminophen induced ALT release (P less than 0.05), which correlated with histologic evidence of centrilobular necrosis. Poly I-C pretreatment produced respective 3-fold and 1.3-fold increases in the production of cysteine and mercapturic acid conjugates (P less than 0.05), which correlated with peak ALT concentrations (cysteine, r = 0.92, P less than 0.001; mercapturic acid, r = 0.75, P = 0.006). Thus, the hepatotoxicity of acetaminophen can be inhibited when given within days after interferon induction, and conversely enhanced when given after several weeks. The toxicologic enhancement appears to be due to increased P-450-catalyzed bioactivation of acetaminophen. PMID- 2262911 TI - Selective blockade of angiotensin responses in the rabbit isolated vas deferens by angiotensin receptor antagonists. AB - We examined the effect of two angiotensin receptor antagonists on neuromodulatory and prostaglandin-producing effects of angiotensin II in the rabbit isolated vas deferens because prior studies have established that angiotensins selectively influence the two neural events, one being adrenergic and the other nonadrenergic. Angiotensin II increased adrenergic neurotransmission and prostaglandin E synthesis in a concentration-dependent manner while depressing nonadrenergic neurotransmission. The [1-Sarcosine, 8-Alanine]-angiotensin II preferentially antagonized adrenergic neuromodulatory effects of angiotensin II. In contrast, the nonadrenergic neuromodulatory and prostaglandin E-releasing effects of angiotensin II were suppressed by [1-Sarcosine, 8-Alanine]-angiotensin II to a lesser extent. The nonpeptide angiotensin receptor antagonist, Dupont 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2(1)-(1-H-tetrazol-5-yl) biphenyl-4 yl)methyl] imidazole, potassium salt, exhibited the opposite selectivity. It eliminated the depression of nonadrenergic neurotransmission without significantly altering the potentiation of adrenergic neurotransmission caused by angiotensin II. The angiotensin-induced stimulation of prostaglandin E synthesis was also eliminated by this antagonist. These data suggest that angiotensin effects in the vas deferens are mediated by at least two types of angiotensin receptors. PMID- 2262912 TI - Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. AB - Acetaminophen (500 mg/kg i.p.) induced hepatotoxicity in fasted ICR mice in vivo. Acetaminophen also caused a long-lasting 50% reduction of the hepatic ATP content, an irreversible loss of hepatic xanthine dehydrogenase activity and a transient increase of the xanthine oxidase activity. All effects occurred before parenchymal cell damage, i.e., the release of cellular enzymes. The hepatic content of GSH and GSSG was initially depleted by acetaminophen without affecting the GSSG:GSH ratio (1:200), however, during the recovery phase of the hepatic GSH levels the GSSG content increased faster than GSH, resulting in a GSSG:GSH ratio of 1:18 24 h after acetaminophen administration. The mitochondrial GSSG content increased from 2% in controls to greater than 20% in acetaminophen-treated mice. The extremely elevated tissue GSSG levels were accompanied by a 4-fold increase of the plasma GSSG concentrations but not by an enhanced biliary efflux, although hepatic GSSG formation and biliary excretion were not affected by acetaminophen. Allopurinol protected dose-dependently against acetaminophen-induced cell injury, the loss of ATP and the increase of the GSSG content in the total liver and in the mitochondrial compartment without inhibiting reactive metabolite formation. High, protective as well as low, nonprotective doses of allopurinol almost completely inhibited hepatic xanthine oxidase and dehydrogenase activity, but only high doses prevented the increase of the mitochondrial GSSG content. The data indicate a long-lasting, primarily intracellular oxidant stress during the progression phase of acetaminophen-induced cell necrosis. The protective effect of allopurinol is unlikely to involve the inhibition of reactive oxygen formation by xanthine oxidase but could be the result of its antioxidant property. PMID- 2262913 TI - Anesthetic effects on glutamate-stimulated increase in intraneuronal calcium. AB - The aim of these investigations was to examine directly with fura-2 microspectrofluorimetry, the effects of general anesthetics on the resting level and glutamate-stimulated increase of intraneuronal free calcium ([Ca++]i) in cultured hippocampal neurons. Media were chosen for the preferential activation by glutamate of either the quisqualate (QUIS media) or N-methyl-D-aspartate (NMDA media) receptor subtypes. Continuous perfusion (20 min) of either media that had been saturated with isoflurane (0.5-4%) or, in some cases halothane (3-4%), produced only small and inconsistent changes in resting [Ca++]i. The rise in [Ca++]i induced by glutamate (or in some cases, NMDA) that was applied in the mainstream of QUIS or NMDA media was attenuated greatly during such applications of isoflurane or halothane for 6 to 20 min. Analysis of concentration-response relationships revealed that the EC50 values for the isoflurane-depressions were 1.7% for the Ca response to glutamate in QUIS media and 1.2% in NMDA media. Application of isoflurane blunted the peak increases in [Ca++]i produced by brief (1 min) applications of 50 mM K. Verapamil (25 microM) did not reduce the resting [Ca++]i and had long-lasting depressant effects on glutamate-stimulated increases in [Ca++]i in NMDA media. The effects of 2% isoflurane and verapamil were approximately additive. These investigations provided evidence that isoflurane reduced the increase in [Ca++]i which resulted from Ca influx linked directly to receptors for glutamate in addition to Ca entry due to activation of voltage gated Ca channels. PMID- 2262914 TI - Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. AB - The hetrazepine WEB 2170 (international nonproprietary name: bepafant), a thieno triazolodiazepine that is structurally related to the recently described platelet activating factor (PAF) antagonist WEB 2086, is a potent and selective PAF antagonist both in vitro and in vivo. WEB 2170 inhibited PAF-induced human platelet and neutrophil aggregation in vitro (IC50 values: 0.3 and 0.83 microM, respectively) but had little or no inhibitory action against aggregation induced by other agonists. The potency in vitro was comparable to that described recently for WEB 2086 (Casals-Stenzel, J., Muacevic, G. and Weber, K.H.: J. Pharmacol. Exp. Ther. 241: 974-981, 1987). When guinea pigs were given i.v. infusions of PAF at 30 ng x kg-1 x min-1, oral (0.005-0.5 mg/kg) as well as intravenous (0.005 0.05 mg/kg) treatment with WEB 2170 abrogated the intrathoracic accumulation of 111In-labeled platelets, the bronchoconstriction and the hypotension as well as the finally occurring death in a dose-dependent fashion. Oral (0.01-1 mg/kg) and intravenous (0.005-0.1 mg/kg) WEB 2170 shared with the beta 2 agonist fenoterol and the steroid dexamethasone the property of protecting elderly NMRI mice from the lethal effect of PAF. In anesthetized rats, intravenous (0.001-0.1 mg/kg) and oral (0.05-1 mg/kg) WEB 2170 inhibited PAF-induced hypotension in a dose-related manner. Coadministration of WEB 2170 inhibited PAF-induced increase of vascular permeability in rat skin very effectively. The half-time of duration of action in the rat was estimated to be about 5 to 6 h after oral administration and about 1.1 to 2.3 h after intravenous application. In conclusion, the hetrazepine WEB 2170 is a strong and selective PAF antagonist, which is in vitro more or less equipotent to WEB 2086. In contrast, in vivo oral WEB 2170 is--depending on the species and considered parameter--about 5 to 40 times more potent against exogenous PAF-induced alterations than the recently described hetrazepine WEB 2086. Particularly in mice and rats, oral WEB 2170 is by far superior to WEB 2086. PMID- 2262915 TI - Rat renal cortical slices demonstrate p-aminohippurate/glutarate exchange and sodium/glutarate coupled p-aminohippurate transport. AB - In isolated basolateral membrane vesicles p-aminohippurate (PAH) transport may be coupled indirectly to the sodium gradient through PAH/glutarate [or alpha ketoglutarate (alpha-KG)] exchange and Na/glutarate cotransport. In this study, rat renal cortical slices were used to examine indirect coupling of PAH transport to sodium in intact renal tissue. Like basolateral membrane vesicles, slices demonstrated avid uptake of 50 microM [14C]glutarate. Steady-state tissue/medium ratios of 30 were achieved by 90 to 120 min. Uptake was inhibited markedly by lithium and fumarate. PAH also inhibited glutarate accumulation, but through acceleration of glutarate efflux i.e., PAH/glutarate exchange, rather than direct inhibition of uptake. PAH-driven efflux of glutarate from slices was blocked by probenecid, which inhibits PAH/glutarate exchange in vesicles. Inasmuch as slices showed both Na/glutarate uptake and PAH/glutarate exchange, externally added glutarate should stimulate PAH uptake in slices. Indeed, in the presence of sodium, 50 microM external glutarate approximately doubled PAH accumulation by the slices. Stimulation by glutarate was abolished by either lithium or fumarate, or by elimination of sodium from the external buffer. The stimulatory effect was specific for glutarate or alpha-KG. Acetate, fumarate and succinate stimulated PAH uptake poorly, if at all. Neither fumarate nor lithium was able to eliminate concentrative PAH uptake completely, suggesting that a portion of PAH transport may occur without Na-dependent glutarate or alpha-KG recycling, i.e., that it may run directly off metabolic alpha-KG production or via a completely glutarate/alpha-KG independent mechanism. PMID- 2262916 TI - Comparison of 4-aminopyridine and tetrahydroaminoacridine on basal forebrain neurons. AB - This study was designed to investigate the ability of 4-aminopyridine (4-AP) and tetrahydroaminoacridine (THA) to reduce several potassium conductances in cells of the medial septum and nucleus of the diagonal band. Intracellular recording and single electrode voltage-clamp techniques were used in an in vitro brain slice preparation. Both 4-AP (100-300 microM) and THA (300 microM) reduced a transient outward current (A-current), whereas only 4-AP increased the release of spontaneous postsynaptic potentials and significantly prolonged action potential duration. High concentrations of THA (1 mM) were needed to significantly increase action potential duration but these levels of THA were still ineffective in eliciting spontaneous postsynaptic potentials. THA (300 microM), but not 4-AP, had the additional effect of reducing time-dependent membrane rectification (Q current) in one cell type. Our results demonstrate that both cholinergic and non cholinergic cells are sensitive to pharmacological concentrations of both compounds. PMID- 2262917 TI - [Toxicity of calcium inhibitors]. AB - Calcium antagonists decrease the intracellular concentration of calcium ions. They act essentially on the smooth vascular muscle, on the cardiac muscle and on the automatic and conducting cells in the heart. At toxic doses these effects induce hypotension, shock and disturbances of sinusal automatism and atrio ventricular conduction. The toxicity of the different calcium antagonists varies according to their tissue specificity. The treatment of overdose includes gastric lavage, oral activated charcoal, cardiorespiratory support, especially alphamimetic vasopressors for shock or hypotension, adrenaline or cardiac pacing for atrio-ventricular block. PMID- 2262918 TI - [Acute diltiazem (DTZ) poisoning. Survey of french poison control centers]. AB - The end-points of this study upon 134 cases reports by the french Poison Centers from 1979 to 1988 (10 years) were to specify the acute toxicity of diltiazem (DTZ). There were 83 self-poisonings in adults, with diltiazem alone (36 cases) or associated with other non cardiotoxic drugs (47), the doses of DTZ ranging from 300 to 5400 mg, and 51 acute accidental overdose in children, the doses of DTZ ranging from 60 to 420 mg. One case of hypotension was observed in a child, without rhythmic disorder, occurring twelve hours post-ingestion of 180 mg of DTZ. In adults, the clinical effects were observed following 360 mg of dose DTZ, occurring 1 1/2 hour post-ingestion. There were discomfort, brady-cardia in 16% of the cases, hypotension in 23% of the cases, cardiogenic shock in 4% of the cases and cardiac arrest in 2.4% of the cases. The rhythmic disorders occurred 2 to 15 hours post-ingestion. There were conduction defects like atrio-ventricular heart bloc I degree in 9% of the cases, II degree in 2.4% of the cases and III degree in 9% of the cases. Less frequently, sinusal bradycardia in 11% of the cases or sino-auricular heart block in 4% of the cases with sometimes auriculo ventricular heart block. These cardiac disorders occurred with 600 mg of DTZ. A cardiac arrest happened in a young healthy man who had absorbed 5400 mg of DTZ. The cardiogenic shocks occurred in patients with an history of coronary on heart disease. The poison removal is likely to prevent the occurrence of clinical or EKG effects when performed within 2 hours post-ingestion, whatever toxic the dose is. The inotropic drugs have been used in 18% of the cases; a percutaneous ventricular pacing was always effective in patients with II or III degree atrio ventricular block or/and cardiogenir shock. These data confirm the data in thirteen patients of the literature. IN CONCLUSION: The acute diltiazem poisoning can occur after 600 mg of DTZ and can induce severe cardiac disorders which can be prevented with poison removal or treated with supportive care. PMID- 2262919 TI - [Acute diltiazem poisoning: kinetic and hemodynamics study]. AB - The authors report three cases of diltiazem overdose with hypotension and atrio ventricular conduction disturbances. Hemodynamic study in 2 cases showed a hyperkinetic state with a decrease of systemic vascular resistances. Diltiazem kinetics studied in 2 cases showed a plasma half life of 5.4 and 8.3 hours, a prolonged absorption until the 28th hours in one case. Treatment included gastric lavage, oral activated charcoal (2 cases), plasma expanders and in 2 cases vasopressors with alpha effects. All three patients recovered. PMID- 2262920 TI - [Acute nicardipine and nifedipine poisoning. Multicenter study. Cooperative study by the french poison control centers and the ARIT]. AB - A study, that was realized by the French Association of Poison Control Centers, tried to estimate the toxicity of Dihydropyridine derivatives towards human beings, in comparison with other calcium antagonists, said to be more toxic. Though, the toxicity of the Dihydropyridine derivatives happens to be far less important considering the rarity or absence of their cardiac effects, it must not however be underestimated in the case of a mass ingestion, or if they are taken simultaneously with psychotropic or cardiotropic drugs. PMID- 2262921 TI - [Acute nicardipine poisoning]. AB - A 41 year old man with overdose of nicardipine is reported. Quickly after the poisoning, he developed a cardiovascular collapse picture with renal failure and myocardium ischemia. The clinical picture improved with injection of dobutamine and dopamine. The hemodynamic study showed a fall of the systemic resistances. The recovery was complete 40 hours after the ingestion. PMID- 2262922 TI - [Acute verapamil poisoning. 6 cases. Review of the literature]. AB - Six cases of acute verapamil poisoning are reported. The dose ingested ranged between 1.2 and 9.6 g. In all cases other drugs had also been ingested and especially betablockers in two cases. Symptomatology included a cardiogenic shock in two cases and an atrioventricular block in four cases. A hemodynamic study in one case showed a cardiogenic shock with increased systemic vascular resistances. The treatment of cardiogenic shock included artificial ventilation, several vasopressors and inotropic agents and cardiac pacing in one case. All patients recovered without sequelae. A toxicokinetic study performed in two cases showed plasma half lives of 7.9 and 13.2 hours, total body clearances of 425 and 298 ml/min. Only 2 to 4.2 per cent of the dose ingested were eliminated in urine. These results confirm the severity of verapamil overdose and the efficacy of symptomatic treatment by inotropic agents. The high rate of spontaneous elimination by hepatic metabolism does not justify drug removal by extra corporeal methods. PMID- 2262923 TI - Exacerbation of hyperlactatemia by infusion of lactated Ringer's solution in dogs with lymphoma. AB - Blood lactate concentrations and acid-base status of six dogs with lymphoma were compared statistically with those from six healthy control dogs before, during, and after a 6-hour infusion of lactated Ringer's solution (LRS). Blood lactate concentrations in dogs with lymphoma were significantly (P less than 0.05) higher immediately before, and at the 1-, 2-, 4-, and 6-hour time periods after infusion when compared with controls. Blood lactate concentrations increased significantly (P = 0.016) after the first hour of infusion in dogs with lymphoma but did not increase in the control dogs. The increase in blood lactate concentrations over baseline values after 1 hour of LRS infusion was significantly (P = 0.008) greater in dogs with lymphoma when compared with controls. Blood lactate concentrations returned to baseline levels after 2 hours of infusion in dogs with lymphoma, suggesting that dogs with lymphoma have a transient inability to handle increased lactate loads when compared with controls. However, the potential to augment lactate use, clearance, or both is present and does occur over time. Blood gas values were not significantly altered within the lymphoma or control dog groups after 6 hours of LRS infusion. Blood bicarbonate concentrations in dogs with lymphoma were significantly decreased before and after LRS infusion when compared with controls. PMID- 2262924 TI - Triiodothyronine (T3) suppression test. An aid in the diagnosis of mild hyperthyroidism in cats. AB - The purpose of this study was to develop a T3 suppression test to help in the diagnosis of mild hyperthyroidism in cats. We evaluated the response in circulating T4 concentrations to exogenous T3 (liothyronine) administration in 44 clinically normal cats, 77 cats with hyperthyroidism, and 22 cats with nonthyroidal disease. The test was performed by first collecting blood samples for basal serum T4 and T3 determinations, administering liothyronine at an oral dosage of 25 micrograms three times daily for seven doses, and, on the morning of the third day, again collecting serum samples for T4 and T3 determinations 2 to 4 hours after the seventh dose of liothyronine. The mean basal serum concentrations of T4 (53.1 nmol/L) and T3 (1.8 nmol/L) were significantly higher in the cats with hyperthyroidism than in the normal cats (T4 = 25.3 nmol/L, T3 = 1.3 nmol/L) and the cats with nonthyroidal disease (T4 = 29.5 nmol/L, T3 = 1.4 nmol/L); however, there was a great deal of overlap of basal values between the three groups of cats. Of the 77 cats with mild hyperthyroidism, 41 (53%) had serum T4 values and 55 (71%) had T3 values that were within the established normal ranges. After administration of liothyronine, mean serum T4 concentrations fell much more markedly in the normal cats and the cats with nonthyroidal disease than in the hyperthyroid cats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2262925 TI - Etoposide (VP-16). Retrospective analysis of treatment in 13 dogs with lymphoma. AB - A retrospective analysis was performed of the effect of VP-16 (etoposide) in the treatment of 13 dogs with lymphoma. Twelve dogs had achieved partial (two) and complete (ten) responses to combination chemotherapy, but all were out of remission at the time of the trial. One dog had not previously had chemotherapy. There was minimal response to VP-16 chemotherapy in the 13 dogs studied, and only two of 13 dogs had some response to treatment. For one dog, complete and partial remission durations were one and three months, respectively. In another dog, there was partial remission of eight days. There were no responses in the other 11 dogs. The most serious adverse reaction after administration of VP-16 was an acute pruritic cutaneous reaction that occurred in 11 of the 13 dogs, which may have been associated with the vehicle of VP-16, polysorbate 80. Results showed that VP-16 has minimal activity for treatment of dogs with lymphoma that have experienced relapses after treatment with other anti-cancer drugs. More trials are needed with higher dosages and the oral form of the drug, which does not contain polysorbate 80. PMID- 2262926 TI - Right dorsal colitis. AB - Moderate to severe ulcerative colitis of the right dorsal colon was diagnosed by necropsy or by exploratory celiotomy and biopsy in 13 horses with a primary clinical complaint of either colic, diarrhea, or weight loss. Clinical signs varied from acute fulminating diarrhea (possibly with fever), colic, dehydration, endotoxic shock and death, to a chronic condition manifested by mild intermittent colic up to several months in duration, and weight loss with or without mild diarrhea. In a large percentage of the horses, those affected had been hypovolemic and received nonsteroidal anti-inflammatory drugs (NSAID) or had received inappropriately high doses of phenylbutazone before the onset of illness. Experimental treatment of two horses with high doses of a phenylbutazone oral paste preparation (6 gm once daily for 5 days) and limitation of their water intake to approximately one half of maintenance requirement (for 5 days) resulted in reproduction of ulcerative colitis involving only the right dorsal colon, which was apparent at necropsy examination 11 and 15 days after initiation of drug use. It was concluded that localized ulcerative lesions in the right dorsal colon may be a previously unreported manifestation of toxicity due to the administration of NSAID. PMID- 2262927 TI - 5-Fluorouracil toxicosis in the dog. AB - Twenty-six cases of accidental 5-fluorouracil (5-FU) ingestions by dogs were reviewed from phone calls to the Illinois Animal Poison Information Center. Cases were collected from January 1, 1987 to December 31, 1988. Of the 26 calls involving 5-FU exposures, 12 were classified as "toxicosis," 13 as "suspected toxicosis," and one as "exposure." Dogs were the only species involved in 5-FU cases received during this time. Accurate estimates of the amount of 5-FU ingested by dogs could be made in 17 cases. Ingestion of more than 20 mg/kg of 5 FU was associated with the development of toxicosis. None of the 12 dogs that ingested oral doses in excess of 43 mg/kg (estimated) survived. Clinical signs associated with 5-FU poisoning in the dog were death, seizures, vomiting (with and without blood), tremors, diarrhea (with and without blood), ataxia, and depression. Clinical signs generally developed within 45 to 60 minutes after exposure, and deaths occurred 6 to 16 hours after ingestion. PMID- 2262928 TI - Endotoxic shock. Part I: A review of causes. AB - Endotoxic shock is a complex phenomenon resulting from systemic release of inflammatory mediators. Endotoxin interacts with inflammatory cells, platelets, and vascular endothelium. Cytokines, such as tumor necrosis factor and interleukins, and lipid mediators (platelet activating factor, thromboxane, prostacyclin, leukotrienes) are released. These primary mediators act synergistically to cause many of the harmful effects associated with endotoxemia. Multiple secondary mediators are released in response to the primary mediators, compounding the damage. The end result is the species-specific clinical syndrome recognized as endotoxemia. PMID- 2262929 TI - Bronchoalveolar lavage in the evaluation of pulmonary disease in the dog and cat. State of the art. AB - Bronchoalveolar lavage is a diagnostic procedure used to obtain specimens representative of disease processes involving the deep lung. Saline is instilled into an airway in sufficient volumes to bathe the alveoli dependent on that airway. The saline is retrieved by suction along with cellular and acellular material lining the epithelial surfaces of the lung. Cytologic and microbiologic evaluation of the fluid can be used to characterize pulmonary diseases in the dog and cat. PMID- 2262930 TI - Modulation of the estrogen receptor structure, evidence of a heterogeneity. AB - In order to analyse the molecular weight polymorphism of the estrogen receptor (ER) in MCF-7 cells, we have developed a procedure which allowed in situ linkage of ER by (3H) tamoxifen aziridine and provided labelled proteins in conditions which minimized protease activities. After labelling, cell lysis was performed in SDS buffer containing various concentrations of [symbol: see text] mercaptoethanol. Proteins extracted with phenolic solution and precipitated by cold acetone were analysed by SDS PAGE. It appears that beside the form of 67 kDa already described, binding entities of tamoxifen aziridine were also present at a molecular mass of 110 kDa and 45 kDa. On the other hand, investigations on the effect of 12-0-Tetradecanoyl Phorbol 13-Acetate (TPA) showed that TPA induces a decrease of the 67 kDa entity. PMID- 2262931 TI - Differential modulation by cations of sigma and phencyclidine binding sites in rat brain. AB - The present investigation attempted to differentiate haloperidol-sensitive sigma sites (sigma H) from phencyclidine (PCP) binding sites in rat brain membranes. We studied the effects of several cations at physiologically relevant concentrations on the binding of radioligands selective for sigma H sites ([3H]haloperidol, [3H](+)3-PPP**), and [3H](+)SKF10,047), or for PCP sites ([3H]PCP and [3H]TCP). The PCP sites displayed a markedly greater sensitivity to cations than sigma H sites. This property was reflected by a greater extent of inhibition of the binding of PCP-selective relative to sigma H-selective ligands at a given cation concentration, as well as by lower IC50's and by steeper slopes of the cation dose-response curves. Divalent cations were approximately 100 times more potent than monovalent cations. All cations were inhibitory, except Sr2+ and Ba2+ which, at micromolar concentrations, enhanced PCP binding but not sigma H binding. Thus, PCP-selective sites appeared to be distinct from sigma H sites with regards to several aspects of cation modulation. This is consistent with the view that PCP and sigma H sites are distinct molecular entities. Further, the marked cation sensitivity of the PCP site is consistent with the current hypothesis according to which the PCP site is linked to the N-methyl-D-aspartate (NMDA) receptor cation channel complex. PMID- 2262932 TI - Binding characteristics of the muscarinic receptor subtype in rabbit pancreas. AB - The muscarinic receptor in the rabbit pancreas was characterized with the use of the labeled ligand (3H)-(-)-quinuclidinyl-benzylate ((3H)-(-)-QNB). Specific binding of (3H)-(-)-QNB to pancreatic acini was found to be reversible and of high affinity, with an equilibrium dissociation constant (KD) of 68 pmol/l and a receptor density (RT) of 170 fmol/mg protein. Agonist binding behaviour was investigated by displacement of (3H)-(-)-QNB binding by eight agonists like arecoline, arecaidine-propargylester (APE) and carbachol, yielding only low affinity binding sites. The inhibition of (3H)-(-)-QNB binding by the selective antagonists pirenzepine, hexahydrosiladifenidol (HHSiD) and (11-[2-[diethyl amino)-methyl)-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyr ido (2,3-b) (1,4) benzodiazepin-6-one) (AF-DX 116) confirmed the M3 nature of the rabbit pancreatic receptor. PMID- 2262933 TI - The role of insulin receptor sulphydryl groups in insulin binding and cellular response in rat adipocytes. AB - Phenylarsine oxide (PAO), an agent which reacts with vicinal sulphydryl groups and dithiothreitol (DTT), a disulphide reducing agent, inhibited insulin binding to intact adipocytes with half maximal inhibition occurring at 28 microM and 340 microM, respectively. Pretreatment of adipocytes with DTT (2mM) prevented insulin stimulation of glucose uptake by approximately 50%. The marked inhibition of insulin binding to adipocytes by PAO and DTT is consistent with the involvement of the receptor cysteine-rich region of hormone binding. Furthermore, DTT inhibition of insulin binding suggests that the integrity of disulphide bridges is critical for insulin binding. The inhibitory effect of DTT and PAO on insulin binding were not additive, instead addition of DTT to PAO-treated adipocytes effected 15% reversal of binding inhibition. The marked inhibition of insulin binding by addition of low concentrations of DTT (0.2-2.0mM) to intact adipocytes is in contrast to the previously reported biphasic response for the effect of DTT on insulin binding to isolated plasma membranes from rat adipocytes (Schweitzer et al. Proc. Natl. Acad. Sci. U.S.A. 77, 4692-4696, 1980). Scatchard plots for 125I-iodoinsulin binding to adipocytes in the basal state were linear. In contrast, Scatchard analysis of insulin binding to plasma membranes prepared from both basal and insulin-stimulated adipocytes yielded severely curvilinear plots. The data suggests that (i) fundamental differences exist between the receptor state in intact cells and isolated plasma membranes and (ii) that a disulphide rich region within the insulin receptor, other than the previously reported class I and class II disulphide bridges, is critical for insulin binding and cellular response. PMID- 2262934 TI - Guanylpirenzepine distinguishes between neuronal ml and m4 muscarinic receptor subtypes. AB - Guanylpirenzepine, a polar, non-quaternary analog of pirenzepine, exhibited a novel binding behavior in rat brain regions: in competition binding experiments against [3H]pirenzepine labeling the M1 receptor in membranes from cerebral cortex, hippocampus and striatum, the compound, differently from pirenzepine, displayed heterogeneous binding curves. Computer assisted analysis of these curves, evidenced the existence of two populations of binding sites: a large proportion (84-89%) of high affinity receptors (KH = 64-92 nM) and a remainder with very low affinity (KL = 19-28 microM). Like pirenzepine, guanylpirenzepine showed low affinity for the glandular M3 and the cardiac M2 receptors when [3H]N methylscopolamine was used to label the receptors in membranes from these two tissues; affinity values for guanylpirenzepine were 1336 and 5790 nM respectively, vs 323 and 683 nM for pirenzepine. We conclude that guanylpirenzepine is able to discriminate between m1 and m4 receptor subtypes and may represent a new tool for deeper studies on muscarinic receptors classification. PMID- 2262935 TI - Effects of charcoal on dissociation kinetics of nuclear and cytosolic steroid receptor complexes from hen oviduct. AB - The observed rate of dissociation of radioactive estradiol from nuclear estrogen receptor complexes from hen oviduct has been shown to depend to a large extent on the method used to initiate dissociation. The present study indicates that nuclear progesterone receptors display the same pattern of behavior. Dissociation kinetics of nuclear progesterone receptor extracted from hen oviducts were affected by the method of initiation of dissociation; the rate of dissociation at 25 degrees C when dissociation was initiated with unlabeled steroid was three times that observed when dissociation was initiated by addition of a charcoal/dextran suspension. In contrast to nuclear receptors, both estrogen and progesterone receptors prepared from cytosol displayed only a single rate of dissociation, no matter what the method of initiation of dissociation. These results strengthen the idea that nuclear receptors contain a factor or subunit which may be removed by charcoal, which alters the rate of dissociation of steroid from the complex. PMID- 2262936 TI - The binding of radioiodinated thrombin to rat promegakaryoblasts. AB - Rat promegakaryoblasts have recently been shown to possess a number of properties of mature platelets. We have studied the binding of 125I-thrombin to these cells grown in culture. The binding was found to be saturable, specific, reversible, and of high affinity. Such cell lines may be useful models for the study of platelet-agonist interactions. PMID- 2262937 TI - Low dose RU486 prevents progesterone antagonism on uterine growth and concomitant type II oestradiol binding induction by oestradiol in rats. AB - The effect of RU486, a synthetic antisteroid, on the antagonism of progesterone (Pg) and dexamethasone (Dex) against oestradiol (Oe) induced uterine growth, and on uterine oestradiol binding (type I and type II sites) was studied in ovariectomized CFY rats. Changes of hypothalamic low affinity [3H]Oe binding have also been evaluated. Inhibitory effects of Pg but not of Dex on uterine growth and type II Oe binding site induction were prevented by RU486. Antiprogestin effect of RU486 could also be demonstrated on low affinity [3H]Oe binding in hypothalami. The inhibitory effect of dexamethasone on type II Oe binding was not opposed by antisteroid, on the contrary, RU486 seemed to potentiate this effect of Dex. Evaluation of type I binding was complicated by the distorting effect of type II binding at the saturation curve. Changes of type I binding seemed to parallel those of type II binding except after Oe+Dex treatment where an increased level of uterine cytoplasmic type I sites and a simultaneous decrease of type II sites were found. Blockage of [3H]Oe binding at high RU486 concentrations was found in vitro in the uterine cytoplasmic fraction. A less pronounced effect was observed in the nuclear fraction. Possible mechanisms of the RU486 effect on type II Oe binding are discussed. PMID- 2262938 TI - Antihypertensive drugs and blood lipids. AB - Hypertension frequently coexists with hyperlipidaemia and it has been suggested that the potential benefits of blood pressure reduction may be compromised if lipid levels are not concurrently reduced. In addition, conventional first line antihypertensive drugs (thiazide diuretics and beta-blockers) produce adverse changes in blood lipids which are most apparent in the short-term but do not entirely disappear during chronic treatment. Of the alternative first-line antihypertensive agents, the calcium antagonist and ACE inhibitor drugs are lipid 'neutral' but only the alpha 1-blockers have been associated with favourable effects on the lipid profile. PMID- 2262939 TI - Major risk factors for coronary heart disease in hypertension: implications for management. AB - Since most deaths attributable to hypertension are the result of coronary heart disease (CHD), the major objective in the management of hypertension should be the prevention of CHD. Data from large population studies, mainly carried out in the USA, leave little doubt that hypertension is causally associated with CHD and we have no reason to believe that the risk factors for CHD in the United Kingdom are any different from those established in the American studies. In addition to the non-modifiable factors of age, sex, and family history, there are modifiable risk factors which include raised serum low density lipoprotein (LDL) cholesterol, smoking, raised BP, diabetes mellitus, lack of exercise, low high density lipoprotein (HDL)-cholesterol, and use of oral contraceptives. Medicine clearly has a large and critical task in dealing with the current epidemic of CHD associated illness. However, it is also apparent from prospective data from several countries that a preventative approach by means of public health measures is likely to have a favourable impact upon several of the modifiable risk factors. It is likely that if resources were made available for this purpose in the United Kingdom, a major reduction in morbidity and mortality from CHD would ensue. If we continue to manage hypertension without paying attention to other CHD risk factors, particularly abnormal lipid profiles, then we are unlikely to make an impact on morbidity and mortality from CHD which is our primary objective. PMID- 2262940 TI - Diagnostic value of Tc-99m MAA radionuclide venography of lower extremity: as a simultaneous procedure of ventilation-perfusion scan for pulmonary embolism. AB - A total of 336 cases received a ventilation-perfusion(V/Q) scan for the detection of pulmonary embolism (PE). Among these, 155 cases simultaneously underwent a successful radionuclide venography study (RNV) of the lower limbs using Tc-99m macro-aggregated albumin (MAA). Concomitant pulmonary arteriography (PA) was performed in 120 cases. Fifty-four of these 120 cases successfully completed the RNV scan. There was a statistical significance in the V/Q scan for the detection of PE as confirmed by the PA (p less than 0.0001). The positive predictive value (PPV) of the RNV for PE was 75% (3/4). The negative predictive value (NPV) was 48% (24/50). The sensitivity and specificity were 10% (3/29) and 96% (24/25) for the 54 patients who had both the RNV scan and PA. For the 155 patients who had simultaneous V/Q and RNV scans, there was no statistically significant correlation between these two scans. The PPV, NPV, specificity and sensitivity were 42%(8/19), 75%(103/136), 90%(103/114) and 20%(8/41), respectively. Despite the low sensitivity and no significance of positive RNV for diagnosis of PE, RNV is still recommendable because it is a simple, non-invasive, simultaneous procedure during perfusion lung scan and has high specificity. PMID- 2262941 TI - [Survey of Enterobius vermicularis infection among school children in Tainan City]. AB - A survey was conducted for enterobiasis, in six primary schools at Tainan city. The survey was conducted in 1986, involving 8,120 school children. The manner of testing, was two consecutive day, adhesive cellophane paper perianal swabs. The test resulted in general infection rate of 30.4%. The positive rates among those primary school children were significantly different (chi 2-test, p less than 0.001). The highest rate (40.3%), was in Shih-Men primary school and the lowest rate (18.7%) in Pao-Jeng primary school. Gender occurrence of enterobiasis was determined by making a statistic analysis between sex. We found significantly higher occurrence in males (32.4%) as opposed to females (28.3%) (chi 2-test, p less than 0.001). The infection rates were also significantly different by grade (chi 2-test, p less than 0.001). The highest rate was found in the lower grades (35.3%), the next in the middle grades (32.4%), and the lowest in the higher grades (21.6%). A questionnaire demonstrated that the family status and personal hygiene are the most important factors in transmission of pinworm infection, among the group surveyed. Moreover, the educational levels, occupations of parents, and facilities of bathrooms, (between both primary schools) were also found significantly associated with the transmission of pinworm infection. Therefore, we believe that these factors play a role in transmission of pinworm infection among school children. PMID- 2262942 TI - [The analysis of motivation and attitude of premarital medical examinees]. AB - The study aims to analyse the motivation and attitude of premarital medical examinees. Ninety-two premarital medical examines, which include 46 self-paid persons and 46 government paid (subsidized by the Department of Health) visited the Family Clinic. They were studied from Oct. 27, 1988 to Nov. 8, 1989. Among 48 male and 44 female examinees, the sex ratio (male:female) was 1.09:1. The predominant age distribution was 26-30 y/o (58.2%); and the predominant level of education was college (54.4%). Questionnaires were sent to these premarital medical examinees. We received 70 questionnaires-47.1% from self-paid, and 52.9% from government paid. The recovery rate was 76.1%. The results of analysis were: 1) Concerning the motivation of examination, 35.1% of self-paid were introduced by relatives or friends; while 50% of government paid were introduced by newspapers; 41.2% of the total response were afraid of genetic disease. 2) Concerning the opinion of the examination fee, there were no significant differences between those of self-paid and government paid. PMID- 2262943 TI - Peritumoral brain edema in intracranial meningiomas. AB - We analyzed 38 patients with 39 meningiomas verified pathologically. The study included 27 females and 11 males. The ages of the patients on admission ranged from 11 to 77 years (averaged 47.6 years). The incidence of brain edema associated with meningiomas was 69%. The extent of peritumoral edema on the CT scans positively related to the duration of preoperative symptoms, the location and size of tumors, and breaching of the cortex by meningiomas. The meningotheliomatous meningiomas were frequently associated with significant brain edema. The ultrastructural features showed some relationship between increased secretory activity and the extent of peritumoral edema. PMID- 2262944 TI - Comparisons of peritoneal function between diabetic and nondiabetic patients with end stage renal disease. AB - Peritoneal function is the major determinant of the efficiency of peritoneal dialysis. To understand whether diabetes affects the peritoneal function, we performed the peritoneal clearance study in 9 diabetic and 16 nondiabetic patients with end stage renal disease. The ultrafiltration volume tended to be lower in diabetics after infusion of 1.5% Dianeal, although there were no statistically significant differences between them. The same results were obtained after infusion of 4.25% Dianeal. The glucose uptake after infusion of both 1.5% and 4.25% Dianeal was not significantly different between the two groups. The dialysate/plasma(D/P) concentration ratio was also not significantly different between the two groups, however the D/P ratio for BUN and uric acid was slightly higher in the diabetic group. The peritoneal clearance of smaller molecules such as BUN, creatinine, uric acid and phosphate also tended to be higher in diabetics after infusion of 1.5% Dianeal for 4 hours. The peritoneal clearance became higher when more hyperosmotic dialysate were used in both diabetics and nondiabetics. The above results indicated that diabetic patients with end stage renal disease might have a normal peritoneal function compared to nondiabetics. PMID- 2262945 TI - Cell surface recognition determinants involved in triggering the lymphokine activated killer cell phenomenon: enhanced killing of modified "anti-self" targets by varying LAK culture conditions. AB - Lymphokine activated killer (LAK) cells were first described by Rosenberg, et al in the early 1980s. In attempting to grow lymphoid cells infiltrating solid tumors, they discovered that such cells, when incubated with the cytokine Interleukin-2 (IL-2), gained the ability to lyse a wide range of auto and allogeneic tumors while sparing normal non-malignant cells. A number of preliminary clinical trials have shown that when LAK cells and IL-2 are infused into patients with end-stage metastatic cancer, impressive tumor regression, and in some cases tumor eradication, can occur, albeit in the face of significant toxicity. Little is understood about how a potential target cell "signals" its malignant character to a LAK cell. Our approach to this problem has been to investigate the role of the absence or modification of certain self antigens which seem to provide LAK cells with a lysis trigger. By manipulating the culture conditions in which the killer cells are grown, we provide evidence that different subsets of LAK cells may lyse different types of tumor targets. These differences may be important in fine-tuning LAK treatment that is more active at the tumor site in vivo and less toxic to patients. PMID- 2262946 TI - Radioprotective effect of free radical scavenging enzymes. AB - Ionizing radiation is an important treatment modality in the management of head and neck squamous cell carcinoma. The superoxide (O2-) and hydroxyl (OH.) radicals produced from oxygen and the radio-hydrolysis of water are responsible for most of the DNA and lipid membrane injury caused by radiotherapy. Superoxide dismutase (SOD) and catalase (CAT) are intracellular enzymes that scavenge the superoxide and hydroxyl radicals respectively. The effect of intravenous SOD and CAT on acute and delayed radiation injury was investigated in a rat model. Catalase was shown to reduce the severity of radiation-induced changes in both the vascular endothelium and squamous epithelium. SOD, alone or with CAT, showed no radioprotective effect. As intravenous catalase does not penetrate intracellularly it should have no effect on the tumoricidal effect of radiation. Further investigation of catalase as an agent to reduce the acute side-effects of radiotherapy is warranted. PMID- 2262947 TI - Aggressive osteoblastoma of the temporal bone: a case report. AB - Osteoblastoma is a rare tumor of bone which is usually present in the long bones and vertebrae. Occasionally, they present in the head and neck, and only very rarely will they have a locally aggressive clinical course. We report a case of the aggressive subtype of benign osteoblastoma and its histologic and radiologic presentation. PMID- 2262948 TI - Desmoplastic fibroma of the temporal bone. AB - A desmoplastic fibroma is a rare entity in the temporal bone. An 86-year-old woman was seen for evaluation of ear discharge and stenosis of the ear canal with a mass involving the post-auricular region. The tumor was found to be a desmoplastic fibroma. The clinical picture, pathology, diagnosis and prognosis of the tumor are discussed. PMID- 2262949 TI - Lymphoma of the zygoma: an unusual cause of unilateral facial swelling. AB - Primary lymphoma of bone is a rare clinicopathological entity, but accurate diagnosis is important as the tumor is usually radiosensitive and associated with a good prognosis when locally eradicated. To our knowledge primary non-Hodgkin's lymphoma of the zygoma has not been previously reported. We describe a case in which the radiographic appearances were misleading and computed tomography (CT) was important in diagnosing a malignant lesion. The differential diagnosis is discussed. PMID- 2262950 TI - The hanging columella. AB - A hanging columella significantly detracts from otherwise pleasing nasal esthetics. Preoperative assessment of the nasal base is crucial to determine the etiology of a pre-existing hanging columella, and to assess the potential for creating such a deformity with rhinoplasty. Prevention or correction of a hanging columella requires surgical techniques that take into consideration the anatomic tip dynamic factors involved. We discuss the anatomy of the nasal base, define the hanging columella, and distinguish this entity from others with which it can be confused. We propose a methodical approach to the evaluation of the hanging columella, and recommend corrective techniques which we have found successful in achieving good cosmetic results. PMID- 2262951 TI - Multielectrode cochlear implantation in children: the Quebec experience. AB - The Quebec Cochlear Implant Research Program has implanted three children since August 1987. This paper reports the results obtained with these children. All of them improved their auditory abilities with cochlear implantation and training. However, the abilities which spontaneously recovered following implantation, the speed of improvement, and the overall level of performance are different from one child to the other. Our data suggest that the age at onset of hearing loss, and possibly the number of years of deafness, may be related to the differences in performance. PMID- 2262952 TI - Psychosocial adjustment after laryngectomy: a review of the literature. AB - This paper reviews the literature on the psychosocial outcomes of a laryngectomy. The largest group of studies focuses on factors which contribute to esophageal speech acquisition, one important measure of rehabilitation outcome. Recently, the technique of tracheoesophageal puncture (TEP) has implicated new directions for studying post-surgical speech recovery. Other studies have defined post surgical adjustment in terms of quality of life or psychological state. Taken together, the research suggests that long-term adjustment for the laryngectomee is shaped by multiple variables, which include: (a) extent of surgery; (b) preoperative visits by a fellow laryngectomee; (c) illness variables; (d) changes in lifestyle following surgery; (e) patient satisfaction with social support; (f) chronic pain, and (g) ability to communicate. We conclude that psychosocial variables contribute substantially to successful post-surgical adjustment. PMID- 2262953 TI - Laser resection of localized subglottic amyloidosis. AB - A case of localized amyloidosis of the subglottis is described. Urgent endotracheal intubation and later tracheostomy were required for upper airway obstruction. The amyloid was completely resected endoscopically using the CO2 laser. There is no evidence of recurrence two-and-a-half years after surgery. PMID- 2262954 TI - Pedunculated intraluminal osteochrondromatous hamartoma of the esophagus. AB - Pedunculated intraluminal hamartoma of the cervical esophagus of an adult female was treated by surgical resection. The patient presented with bloody sputum. A barium swallow revealed a pedunculated intraluminal tumor just below the conus of the thyroid cartilage. The tumor had a stalk of 6 cm in length and was attached to the cricopharyngeal muscle. Histopathologic examination showed a predominance of osseous and cartilaginous tissue. The tumor also contained fibrous tissue, adipose tissue and glandular structure. The embryology of such a cartilaginous tumor at the proximal esophagus was interesting. PMID- 2262955 TI - The use of long-acting penicillin in the prophylaxis of recurrent tonsillitis. AB - The authors report a study designed to explore the usefulness of long-acting penicillin in the management of recurrent tonsillitis. The trial, conducted in Sri Lanka, involved 179 patients aged 2 to 20 who had suffered multiple attacks of tonsillitis annually. The results showed a significant reduction in the number of attacks of tonsillitis experienced by the treated group, especially those aged 5 to 11, resulting in a drop in the number requiring tonsillectomy. PMID- 2262956 TI - Ozena revisited. AB - Primary atrophic rhinitis or ozena is a chronic nasal disease characterized by progressive atrophy of the nasal mucosa and underlying bone, accompanied by the formation of foul smelling, thick, dry crusts in the greatly enlarged nasal cavities. Although the incidence of ozena is greatly diminished in the western world, it is still encountered rarely and merits the attention of the ENT specialist. Hereditary, infectious, developmental, endocrine and nutritional factors have been implicated but the etiology of ozena still remains enigmatic. Numerous surgical and non-surgical methods have been advocated for treatment of ozena. We review our experience with 17 ozena patients in the past 20 years and discuss different modes of treatment. The relevant literature is reviewed. PMID- 2262957 TI - The mandibulotomy splint. PMID- 2262958 TI - A pseudo-malignant Warthin's tumor presenting with facial nerve paralysis. AB - Facial nerve paralysis, in association with a parotid mass, is generally considered pathognomonic of malignancy. However, nine cases of paralysis with benign tumors have been reported: four in association with a pleomorphic adenoma, three with a Warthin's tumor and one with an oncocytoma. The details of these cases are described and an additional case of Warthin's tumor causing a facial paralysis is reported. In all four cases of Warthin's tumor the pathology is similar, with inflammation, fibrosis and necrosis, especially in areas surrounding branches of the facial nerve. In view of the 10 cases reviewed herein, it is suggested that the pathology be confirmed at the time of surgery and every effort made to preserve facial nerve function. PMID- 2262959 TI - MRI in cervical lymph node staging. PMID- 2262960 TI - [Susceptibilities of uropathogenic bacteria to ampicillin, cefazolin, cefmetazole and gentamicin. Nine-year survey of changing patterns of susceptibilities]. AB - We analyzed antibiotic susceptibilities of urinary isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, and Indole (+) Proteus group to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) in 69 laboratories in 1988 and also studied changing patterns of susceptibilities from 1980 to 1988. Minimal inhibitory concentrations were determined using the agar dilution method (MUELLER-HINTON agar, BBL) with inoculation of 10(6) cfu/ml of bacteria. Ninety to 99% of the strains of E. coli, Klebsiella spp. and P. mirabilis were inhibited at a concentration of 6.25 micrograms/ml of CEZ and CMZ and of 1.56 micrograms/ml of GM. Approximately 80% of the strains of Indole (+) Proteus group were inhibited at concentrations of 6.25 micrograms/ml of CMZ and of 1.56 micrograms/ml of GM. However, resistance to ABPC and CEZ was high, with 83% and 81% of the strains being not inhibited at a concentration of 50 micrograms/ml of ABPC and CEZ, respectively. No significant changes in susceptibilities of the 4 bacteria to the above 4 antibiotics were observed over the 9 year period. No increase was found in the incidence of the resistant strains of the 4 bacteria to CMZ and GM, nor of E. coli and Klebsiella spp. to CEZ. PMID- 2262961 TI - [Microbiological assay method of BMY-28100 and some other cephem antibiotic in serum and tissues. Development of new sample preparation with Evan's blue, a high albumin binding dye]. AB - With a new simple sample pretreatment, microbiological assay methods for quantitative determination of BMY-28100 and some other cephem antibiotics in serum and tissues have been developed. Presented sample pretreatment was founded on the extraction with Evans' blue, a high serum protein binding dye, and the ultrafiltration using cellulose membrane (Millipore; MW cutoff is 10,000) to which Evans' blue was specifically absorbed. Regardless of sample media, antibiotic contents in filtrates were determined accurately using calibration curves based on standard solutions prepared with 1/15 M phosphate buffer, pH 7.4. Four cephems, ceftriaxone (CTRX), cefazolin (CEZ), BMY-28100 and cefadroxil (CDX) were examined in human serum and rat liver tissues. Corrections were made for antibiotic recoveries into 1/15 M phosphate buffer, pH 7.4. CTRX, CEZ, BMY-28100 and CDX in serum and tissues were recovered into buffer at rates of 98.4-101.6%, 97.6-102.0%, 99.8-101.4% and 97.5-98.2% of of spiked (theoretical) values, respectively regardless of antibiotic concentrations. Furthermore, these concentrations obtained using the present bioassay method were well in agreement with those obtained by the HPLC method. When BMY-28100 was administered to volunteers, concentrations of BMY-28100 in serum obtained by the present bioassay method were well in agreement with those obtained by the usual bioassay method which required the fresh human serum to prepare the standard solutions. PMID- 2262962 TI - [Clinical laboratory approach to estimate effective administrative dose of minocyclin. Reevaluation of in vitro MIC break points in disc susceptibility test]. AB - Antimicrobial activities of minocycline (MINO) against various clinical isolates, 270 strains obtained in 1988, were determined and the reliability of the MINO disc susceptibility test in estimating approximate values of MICs was studied. Clinical significance of a 4 category system for the interpretation of the disc tests, which is widely used in Japan, and that of a 3 category system used in the USA and Europe, were also evaluated to determine which system would be more suitable for the evaluation of proper dose levels of administration. In this study, MICs were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. MIC80 values of MINO against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae were all less than or equal to 0.78 micrograms/ml. Those against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were 0.39, 6.25, 3.13, 25, 50 micrograms/ml, respectively. MIC80 values against Pseudomonas aeruginosa, Serratia marcescens, Enterobacter spp., and Citrobacter spp. were 50, 100, 50 and 12.5 micrograms/ml, respectively. The inhibition zones obtained with the disc method were compared with MICs. The results of MINO disc susceptibility test either with 200 micrograms disc (Showa) or 30 micrograms disc (prepared in this laboratory) were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs. In the 4 category classification system currently used, break points in MIC values proposed are ( ) MIC less than or equal to 2 micrograms/ml, (++) MIC greater than 2-10 micrograms/ml, (+) greater than 10-50 micrograms/ml, (-) MIC greater than 50 micrograms/ml. The results obtained with 200 micrograms and 30 micrograms discs showed false positive in 26.6% and 20.5% of the samples, and false negative in 5.8% and 23.6% of the samples, respectively. The disc results of S. aureus, S. epidermidis, S. pneumoniae, etc. were relatively well classified, but those of E. coli, K. pneumoniae, Proteus spp. were not, showing more false positive results. Changing the lower 2 MIC break points in the 4 category system to: ( ) MIC less than or equal to 3 micrograms/ml and (++) MIC greater than 3-15 micrograms/ml, the false positive results with both 200 micrograms and 30 micrograms discs were reduced to 12% and 6.2%, respectively. The false negative results were 5.8% and 23.6%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2262963 TI - [Clinical laboratory approach in estimating effective administrative dose of piperacillin. Reevaluation of MIC break points in 3 and 4 category systems of disc susceptibility test]. AB - The reliability of the piperacillin (PIPC) disc susceptibility test in estimating approximate values of MICs was studied with various clinical isolates totaling 284 strains using Showa discs and the discs prepared in this laboratory (both 8 mm diameter containing 30 micrograms of PIPC). Clinical significance of a 4 category system for the interpretation of the PIPC disc tests, which is widely used in Japan, was reevaluated to determine whether this system would be suitable or not for the evaluation of proper dose levels of administration. Break points in MIC values proposed for the classification of bacteria into 4 categories of susceptibility were: ( ) MIC less than or equal to 3 micrograms/ml, (++) MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. A 3 category system for interpreting of disc test, which is generally used in the USA and Europe, was also evaluated. MIC break points in the 3 category system proposed for the classification of the PIPC test are sensitive (S) MIC less than or equal to 64 micrograms/ml and resistant (R) MIC greater than or equal to 256 micrograms/ml. In addition, British Society for Antimicrobial Chemotherapy recently proposed in vitro MIC break points for PIPC in therapeutic use, recommending MICs 16 and 64 micrograms/ml. MIC 16 micrograms/ml can be used for general infections treated with usual administrative doses for such infections and MIC 64 micrograms/ml may apply to increased dosage or to normal dosage when PIPC is locally concentrated (mainly urinary or biliary tract infections). The results obtained with the disc method were compared with MICs determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. The results of the PIPC disc susceptibility test either with Showa discs or discs prepared in this laboratory were well correlated with MICs, showing the reliability of the disc method in estimating approximate values of MICs. In the 4 category classification system of the Showa disc test, 33 out of 284 strains (11.6%) tested showed false positive results and 5 strains (1.8%) false negative results. Similarly, in the test of 30 micrograms discs prepared in this laboratory, of 284 strains 26 (9.2%) showed false positive results and 8 (2.8%) false negative results. In the tests of Showa discs and discs prepared in this laboratory, both containing 30 micrograms of PIPC, no inhibitory zones were observed against the strains with MIC greater than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2262964 TI - [Study on effects of cefminox sodium on blood coagulation system]. AB - Effects of cefminox (CMNX) on hemostasis and blood coagulation system were studied. Adult in-patients admitted to 237 centers (310 clinics) nationwide in Japan during the period from April 1988 to March 1989 were followed up using a newly designed uniformed protocol. Case cards recovered were inspected by an evaluation committee and patients to be included in analysis were determined according to the protocol. Presence or absence of abnormalities in the hemostasis and blood coagulation system was examined objectively using criteria for evaluation prepared by the committee. Out of 1,374 patients included in analysis, 10 patients were judged as having abnormalities which were suspected to have causal relationships with CMNX. Prolongation in prothrombin time was observed in 4 cases (0.29%), prolongation in activated partial thromboplastin time in 4 cases (0.29%), and decrease in fibrinogen in 2 cases (0.15%). Decrease in platelet count was not detected in any of the cases. Cross-sectional analysis according to background factors in these 10 cases revealed that abnormalities of the hemostasis and blood coagulation systems were significantly higher (P less than 0.01) for the group positive for underlying disease or complications ("positive" group) than the "negative" group. Five out of 9 patients of the positive group had malignant neoplasm. Other than this factor, no items showed statistically significant differences. From these results it is considered that the administration of CMNX is nearly free of effects on the hemostasis and blood coagulation system and development of laboratory abnormalities is chiefly due to the patients' condition. PMID- 2262965 TI - [Laboratory and clinical studies of cefodizime in pediatric field]. AB - We have carried our laboratory and clinical studies on cefodizime (CDZM, THR 221). The results were summarized as follows. CDZM was given by 30-minute drip infusion to 2 children at a single dose of 10 mg/kg and to 2 children at a single dose of 20 mg/kg and to 3 children at a single dose of 40 mg/kg. After the 30 minute drip infusion, mean serum levels of CDZM obtained for the 3 dose levels were 76.16 +/- 5.52 micrograms/ml, 170.49 +/- 16.70 micrograms/ml, 270.01 +/- 50.44 micrograms/ml at the end of injection, respectively, and serum half-lives were 2.03 +/- 0.78 hours, 2.03 +/- 0.38 hours, 2.28 +/- 0.30 hours, respectively. The mean urinary excretion rate of CDZM were 83.3 +/- 22.3%, 73.1 +/- 13.9%, 51.1 +/- 8.5% in the first 8 hours after the 30-minute drip infusion of 10 mg/kg, 20 mg/kg, 40 mg/kg, 40 mg/kg, respectively. Treatment with CDZM was made in 28 cases of pediatric bacterial infections; 5 cases of tonsillitis, 2 cases of bronchitis, 10 cases of pneumonia, 6 cases of enteritis, 3 cases of urinary tract infection and 1 case each of maxillary sinusitis and laryngitis. Results obtained were excellent in 13 cases, good in 7 cases, fair in 2 cases, poor in 6 cases. No significant side effect due to the drug was observed except one case of thrombocytosis and 2 cases each of elevated GOT and elevated GOT and GPT. PMID- 2262966 TI - [Clinical evaluation of combination therapy with aspoxicillin and ceftazidime for severe infections complicating hematological disorders]. AB - Clinical effects of a combination therapy using aspoxicillin (ASPC) and ceftazidime (CAZ) were investigated in 88 patients with severe infections which were complicating hematological disorders. ASPC and CAZ were administered intravenously at daily doses of 8 g and 4 to 6 g, respectively, in 2 to 4 divided doses for at least 3 days. The treatment was markedly effective in 20 cases; effective in 31; fairly effective in 4; and ineffective in 33 cases. Seventy seven patients with whom detailed data were obtained showed an efficacy rate of 63.6%. Bacteria were detected in 9 patients, from whom 10 strains were isolated. The results of bacteriological effects were: 3 strains disappeared, 1 decreased, 3 unchanged, and 3 unclear. The bacteriological eradication rate was 42.9%. Of the detected 10 strains, 3 were identified as Pseudomonas aeruginosa, with 2 of the 3 strains eradicated and 1 decreased. An evaluation of the relationship between clinical efficacies and neutrophil counts before and after the ASPC-CAZ combination therapy showed that the patients with 500/mm3 or higher neutrophil counts before the therapy or those with increased neutrophils after the therapy tended to be more responsive to the therapy. Side effects were observed in 4 patients, but all of them disappeared upon discontinuation of the therapy. The combination therapy with ASPC and CAZ appears to be useful for the treatment of severe infections complicating hematological disorders. PMID- 2262967 TI - [A clinical study on S6472, sustained release preparation of cefaclor, dermatological area]. AB - We conducted a clinical investigation on the use of S6472, an sustained release preparation of cefaclor, in the dermatological area. Thirty-two patients serving as subjects were divided into group I (14 cases, including folliculitis and acne pustulora), group II (16 cases, including furuncle, furunculosis and carbuncle) and others (2 cases). One or 2 wrappers (375 or 750 mg) of S6472 were orally administered to patients twice daily after meals. In group I, the efficacy rate was 100%. Clinical results were as follows: Excellent (6 cases), good (8 cases), fair (0), and poor (0). In group II, the efficacy rate was 93.8%: Excellent (10 cases), good (5 cases), fair (1 case), and poor (0). A decrease of the bacteriological effect was observed in 1 case with Staphylococcus epidermidis. A superinfection was noted in 1 case Staphylococcus aureus. The causative bacteria were all eradicated in the remaining 24 cases. No side effects were detected. From the above results, S6472 appears to be a useful preparation, twice daily oral administration has excellent effects against dermatological infections. PMID- 2262968 TI - [Basic and clinical studies on norfloxacin in the pediatric field]. AB - Pharmacokinetic , bacteriological and clinical studies on norfloxacin (NFLX), a quinolone-carboxylic acid antibacterial agent, were conducted in the pediatric field. 1. Serum concentrations and urinary excretion of NFLX after single dose of 2.2 approximately 5.6 mg/kg (mean 4.4 +/- 1.2 mg/kg) were determined in 13 children with ages between 6 and 11 years. The mean peak serum concentration of the drug was 0.37 +/- 0.20 micrograms/ml at 2 hours after administration. The mean half-life of the drug in serum was 2.8 +/- 0.4 hours and the serum concentration at 8 hours was 0.11 +/- 0.06 micrograms/ml. The mean urinary concentration reached a maximum of 125.2 +2- 166.2 micrograms/ml in pooled urine from 0 to 2 hours and the mean urinary recovery rate in the first 8 hours after administration was 22.1 +/- 6.0%. A dose-response relationship was observed between doses/body weight and peak serum concentrations. 2. The clinical efficacy, bacteriological efficacy and the safety of NFLX were evaluated in 65 pediatric patients with ages between 2 years 10 months and 15 years 7 months with infections. In 62 assessable cases (acute purulent tonsillitis 9 cases, acute pneumonia 3 cases, chronic rhinitis 1 case, urinary tract infections 15 cases, and acute colitis 34 cases), clinical efficacies were excellent in 48 cases, good in 13 cases, and fair in 1 case with an overall efficacy rate of 98.4%. Staphylococcus aureus 1 strain, Staphylococcus epidermidis 1 strain, Escherichia coli 10 strains, Salmonella sp. 5 strains, Morganella morganii 1 strain, Pseudomonas aeruginosa 3 strains, Haemophilus parainfluenzae 1 strain and Campylobacter jejuni 12 strains were isolated from the patients as pathogens. Bacteriologically, all of these strains were eradicated except that 3 strains of C. jejuni only decreased. With regard to side effects, dizziness and nausea were observed in 1 case each but they were slight and the continuation of the treatment was possible. No abnormal laboratory test data were observed. From the above results, NFLX was considered to be a useful drug for the treatment of pediatric infections. PMID- 2262969 TI - [Pharmacokinetic and clinical studies on isepamicin in chronic complicated urinary tract infection using daily single dose treatment]. AB - To assess the usefulness of single dose treatment with isepamicin (ISP) against chronic complicated urinary tract infection (CC-UTI), laboratory and clinical studies were carried out. The results are summarised as follows. 1. Serum concentrations. Serum concentrations of the drug were assayed for patients after the administration of ISP at a dose of 400 mg by intravenous drip infusion for 30 or 60 minutes. Patients tested consisted of 3 groups with different degrees of renal functions (Ccr: ml/min); 1) normal, 130.8, 2) slightly impaired, 70.8, 3) moderately impaired, 45.9. When the peak/trough concentrations in the 3 groups were compared on 1st-2nd day/5th-6th day of the administration, no significantly different values were recognized among the 3 groups in the peak/trough concentrations. 2. Clinical efficacy Twenty three patients including 18 (78%) patients over 61 years of age were treated at a dose of 400 mg once a day for 4 10 days. Of 21 evaluable cases, 15 (71%) were evaluated as excellent or moderate according to the Japanese UTI criteria. Against the clinical isolates, 21 (68%) out of 31 strains were eradicated after the treatment. 3. Safety Neither subjective side reactions nor clinical abnormal values were encountered throughout the treatment. 4. Conclusions The clinical effectiveness of daily single dose treatment with ISP (400 mg once a day, i.v.d.) was considered to be almost comparable to the treatment with 200 mg twice a day. Furthermore, since no problems on safety were noted even in treating aged patients with slight to moderate renal impairments, the drug appears to be evaluated as highly useful. PMID- 2262970 TI - [Pathophysiological analysis of cardiac function by computer processing of echocardiograms]. AB - Automatic image processing system has been developed for analysis of cardiac function with echocardiograms. Echograms of apical long axis view were transferred to microcomputer system and processed to display three dimensional images of left ventricular myocardium. With this technology, analysis of left ventricular wall thickness in three dimensional manner revealed pathophysiological changes in ischemic heart disease. PMID- 2262971 TI - [Patho-physiological analysis on peripheral circulation using thermography as an example of functional body imaging]. AB - The various body imaging systems can be classified into structural body imaging and functional body imaging. Thermography is a typical example of the latter category. Thermography is regarded to mainly represent peripheral circulatory function on hands and feet. We have studied the patho-physiology of peripheral circulation in normal subjects and in patients with diabetic microangiopathy, using the thermography system. Analysis of the cold loading test by thermography revealed that the recovery after cold loading was decreased with aging in healthy subjects. In diabetic patients, recovery after cold loading was apparently lower than in senile healthy subjects on foot. Thermography was also considered as a useful tool for evaluation of the effect of medicines such as PGE1, in a long term study, as well as single dose test. Furthermore, thermography proved to be the first choice study in serious peripheral circulatory failure such as diabetic gangrene, since it is a non-invasive and non-contact examination. PMID- 2262972 TI - [Recent development of determination methods for adrenocortical hormones and catecholamines]. AB - Newly developed resins and high-performance liquid chromatography (HPLC) with column switching technique have enabled on-line solid-phase extraction, purification and derivatization for highly sensitive determination in recently developed determination methods for serum cortisol, urinary 17-ketosteroids (17 KS), urinary conjugated 17-KS fractions and urinary free catecholamines (CA). These methods are (1) determination of serum cortisol by HPLC with a BSA-ODS column (TSK) and serum sample direct injection, (2) determination of fluorescently derivatized serum cortisol with sulfuric acid and ethanol by column switching HPLC, (3) determination of urinary 17-KS with no need of previous hydrolysis of the conjugated forms, (4) HPLC of conjugated 17-KS fluorescently prelabelled with dansyl hydrazine, (5) HPLC of urinary free catecholamines (CA) with on-line extraction using a cation exchange column and on-line fluorescent derivatization with 1,2-diphenylethylenediamine, (6) ion pair HPLC of urinary free CA with on-line extraction using a hard boric acid gel column and postcolumn trihydroxyindole derivatization, and (7) HPLC of urinary free CA with on-line extraction and solid-phase derivatization using a boric acid gel column, o phthalaldehyde and 2-mercaptoethanol, have achieved no previous or simple sample extraction, more rapid, accurate and higher sensitive determination comparison with ordinary methods for these substances and furthermore, some methods have enabled fully automated analysis. PMID- 2262973 TI - [Lipoprotein metabolism analysis in arteriosclerotic diseases]. AB - Lipoprotein metabolism was studied by analyses of apolipoproteins, cholesterol content in lipoproteins and electrophoresis. The findings obtained suggested that the apolipoprotein levels such as A1 and B are related with particle number of lipoproteins such as HDL and LDL, while cholesterol content in lipoproteins is affected by qualitative change in particles as well. In patients with diabetes mellitus (NIDDM), LDL cholesterol correlated with HbA1c, and cholesterol and apolipoprotein B in the beta-area on electrophoresis showed accelerated mobilities, which were mimicked by in vitro glycation of LDL. In coronary heart diseases, elevation of apolipoprotein B and a low level of HDL cholesterol were general findings. The B/A1 ratio could be a sensitive indicator for these diseases. Hyper HDL cholesterolemias, excluding the patients with prostatic cancer who had undergone estrogen-treatment, showed elevated levels of apolipoprotein E in alpha 2-area on electrophoresis. Heterogeneity in Hyper HDL cholesterolemia was implicated. Qualitative analysis of lipoproteins by our method is believed to be useful. PMID- 2262974 TI - [Clinical significance of determination of serum RNase activities in patients with eosinophilia--II. Measurements using polyuridylic acid and polycytidylic acid as substrates]. AB - The activities of RNase (RNase-U and RNase-C) were determined in the serum and leukocytes of 277 patients with 14 cases of various kinds of eosinophilia (not less than 10(3)/microliters), 28 cases of chronic myelocytic leukemia (CML), using polyuridylic acid and polycytidylic acid as synthetic substrates according to the method of Raddi et al. Serum RNase-U activity, serum RNase-C activity and the activity ratio (U/C x 10(-3)) were 55 +/- 14 U, 1,280 +/- 235 U and 44 +/- 11 (mean +/- SD), 196 +/- 137, 1,992 +/- 1,134 U and 97 +/- 38, and 110 +/- 50 U, 1,854 +/- 625 U and 65 +/- 13 for normal subjects, eosinophilia and CML (untreated), respectively. U/C ratio in eosinophilia and CML (untreated) showed a highly significant positive correlation (p less than 0.001) with peripheral eosinophil count; the activity of serum RNase-U per cells in the supernatant of eosinophil homogenate rose significantly (p less than 0.001) compared with that of lymphocytes or granulocytes. Besides, serum and eosinophil RNase-U had a similar optimal pH. These results suggested that serum RNase-U in eosinophilia originated mostly from eosinophils and its rise was correlated strongly with the increase in eosinophils. PMID- 2262975 TI - [Early detection of successful reperfusion by analysis of serum myoglobin in patients with acute myocardial infarction]. AB - We examined the changes of serum myoglobin (Mb) levels after reperfusion therapy (PTCR, PTCA) in 24 patients with acute myocardial infarction by latex agglutination turbidimetry. In the cases of 13 patients successfully reperfused, significantly higher Mb levels was observed and they disappeared rapidly from blood after the therapy. On the other hand, serum Mb levels disappeared slowly in the cases of patients unsuccessfully reperfused. The disappearance rate of Mb (23.4 +/- 6.7%) in successful reperfused patients was higher than that in unsuccessful reperfusion (5.3 +/- 6.8%) (p less than 0.001), the cut-off value of serum Mb levels in the decision regarding success or failure of reperfusion was set at 17% of disappearance rate, the predictive values for successful and unsuccessful reperfusion were 92% and 91% respectively. The maximum peak time of CK, CK-MB activities and Mb levels after onset of chest pain were also observed. Only the maximum peak time of CK-MB was significantly fasten than others in the cases of patients sera with successful reperfusion (p less than 0.05). We conclude that the measurement of serum Mb levels was useful and suitable for rapid judging on success or failure of reperfusion therapy by use of the disappearance rate of it. PMID- 2262976 TI - [Studies of normal values and prediction equations for pulmonary function- spirometry and flow-volume measurements in healthy Japanese children 6 to 14 years of age]. AB - We analyzed spirometric data (spirograms and flow-volume curves) on 1,357 healthy Japanese children (6-14 yr, 709 males and 648 females) in Higashimatsuyama, Saitama. The area was selected as the representative of the less polluted area in Japan, as we intended to exclude possible effects of air-pollution on spirometric values. Hot-wire anaemometers (AS 3500, AS 4500, MINATO) were used in the spirometry and the test procedures were done following the American Thoracic Society recommendations. By multiple regression analysis prediction equations were obtained for VC, FVC, FEV1, FEV1/FVC (%), MMFR, PEFR (Peak Expiratory Flow Rate), V75, V50, and V25. The selected variables were height and weight for VC, FVC and FEV1 but only height for MMFR, PEFR, V75, V50 and V25. Since there was no significant correlations between FEV1/FVC (%) and these variables, we defined normal ranges for FEV1/FVC (%). The predicted values derived from our equations were larger than those obtained from the other studies published in Japan. The difference is probably due to the improvement in the body size of Japanese children and the equipments used. PMID- 2262977 TI - [A case of nephrotic syndrome with abnormally high level of protein C induced by prednisolone]. AB - Adrenocortical hormones have been used for nephrotic syndrome from 1950. But effects of these drugs in coagulation and fibrinolysis are unknown in detail. We studied the effect of prednisolone in a patient with nephrotic syndrome. Protein C increased remarkably after administration of prednisolone 40 mg/day and then decreased in parallel with the dose of prednisolone. Factor X increased more slowly than Protein C. On the other hand, we couldn't find increase of Protein S. Our results indicate that prednisolone have anticoagulant effect by promotion of production of Protein C. PMID- 2262978 TI - [A case of holoprosencephaly with a flat electroencephalogram]. AB - A case of alobar type of holoprosencephaly, a severe impairment of the development of central nervous system, is presented. This is a case report of 2 month-old boy who had a peculiar physiognomy with a microcephalus and an undeveloped forehead. Echoencephalography showed a defect of almost all cerebellum and a singular ventricle accompanied with severe hydrocephalus. However, his brain stem and cerebellum could be confirmed. His electroencephalogram showed complete flat waves and failed to respond to visual evoked potential test (VEP) and auditory brain stem response test (ABR). Any chromosomal abnormalities were not found. PMID- 2262979 TI - [Present status of radiographic diagnosis of colonic diseases]. PMID- 2262980 TI - [Epidemiologic study of colonic diseases in Japan]. PMID- 2262981 TI - [Clinical and epidemiologic study of colonic diseases]. PMID- 2262982 TI - [Pathologic diagnosis of colonic adenoma and adenocarcinoma]. PMID- 2262983 TI - [Radiographic techniques, patient preparation and contrast media]. PMID- 2262984 TI - [Comparative study of radiographic and colonoscopic diagnosis of colonic diseases]. PMID- 2262985 TI - [Radiographic diagnosis of ulcerative colitis]. PMID- 2262986 TI - [Radiographic diagnosis of Crohn disease ]. PMID- 2262987 TI - [Radiographic diagnosis of colonic tuberculosis]. PMID- 2262988 TI - [Radiographic diagnosis of infectious colitis and antibiotics-associated colitis]. PMID- 2262989 TI - [Radiographic diagnosis of ischemic colitis]. PMID- 2262990 TI - [Radiographic diagnosis of colonic ulcer and Behcet's syndrome]. PMID- 2262991 TI - [Radiographic diagnosis of colonic polyps]. PMID- 2262992 TI - [Radiographic diagnosis of intestinal polyps ]. PMID- 2262993 TI - [Radiographic diagnosis of villous tumor of the colon]. PMID- 2262994 TI - [Radiographic diagnosis of benign colonic tumors excluding adenoma]. PMID- 2262995 TI - [Radiographic diagnosis of colonic neoplasms in early stage]. PMID- 2262996 TI - [Radiographic diagnosis of progressive colonic neoplasms]. PMID- 2262997 TI - [Radiographic observation of progressive process of colonic cancers]. PMID- 2262998 TI - [Radiographic diagnosis of colonic sarcoma]. PMID- 2262999 TI - [Radiographic diagnosis of colonic carcinoid tumor]. PMID- 2263000 TI - [Radiographic diagnosis of patients with various colonic diseases]. PMID- 2263001 TI - [Simple abdominal radiography for diagnosis of colonic diseases]. PMID- 2263002 TI - [Angiographic diagnosis of colonic diseases]. PMID- 2263003 TI - [Computed radiography of colonic diseases]. PMID- 2263004 TI - [Endoscopic ultrasonography of colonic diseases]. PMID- 2263005 TI - [CT and MRI diagnosis of colonic diseases]. PMID- 2263006 TI - [Mass screening of colonic neoplasms]. PMID- 2263007 TI - [Pneumonia in the elderly]. PMID- 2263008 TI - [Cataract in the elderly]. PMID- 2263009 TI - [Presbyacusis]. AB - Presbyacusis is senescence in the auditory system. Currently, the etiology of presbyacusis is thought to be mainly due to environmental noise and arterial sclerosis. Cumulative effects of social noise influence the auditory function gradually. Sclerotic change of arteries in the brain occurs along the total auditory pathway. Histopathological findings reveal characteristic changes in all parts of the auditory pathway in elderly persons. Alterations include thickening of the ear drum, sclerotic change of the ossicles joint, decreasing number of hair cells, degeneration of the eighth nerve and of the neurons in the auditory center. Pure tone audiograms show gradually progressive sensorineural hearing loss at high frequencies due to lesions characteristic of senescence. During the 30's the threshold at 8 KHz increases a little, but in the 60's the pure tone threshold increases over all frequencies. The maximum speech discrimination parallels the drop in the pure tone threshold level. In contrast to the normal speech discrimination score, the speech discrimination score using frequency distorted words is very low in senile persons. There is no known therapy for presbyacusis. Hearing aids compensate hearing impairment to some extent, but patient's adaptation to hearing aids is undetermined. PMID- 2263010 TI - [Breathlessness of the elderly and its managements]. AB - It is certainly difficult to understand the clinical significance of dyspnea or breathlessness among the elderly, though this symptom is quite routine. Setting a conjugate of the dyspnea index as an indicator of ventilatory reserve ratio, its distribution was tested along an age abscissa upon the twenty senile dyspnea and demonstrated almost all of them below the 30% level. Their arterial blood oxygen tensions were grouped onto the severity rank of dyspnea, clarifying that some senile lived of no complaint by the blood oxygen tensions within the range of pulmonary insufficiency, despite there some reluctant by the normal blood gas tensions. In order to comprehend this evidence, the dyspnea was dissected into several raising factors, each of which was examined the manner how a set of organs in the respiratory system of the elderly to be concerned under aging effects and to be detected in measurement. Respiratory center drive behaves in response to the efficacy of ventilation apparatus, so in resting state it supports by minimum activity without sensation of breathing difficulty, but at needs it works more even in dyspnea, the sensation of which deepens less itself together with increment of oxygen consumption. Considerable causes of this symptom for the senile may be due to hyperventilation syndrome, lung embolism after bone fracture, diabetic pulmonary capillopathy and hypophosphatemia. The treatments of senile dyspnea shall require the exact estimation of causal seriousness and not only attain improvement of pulmonary impairments and its accessory setups but also psychophysical rehabilitations upon rational nutrient preservation. PMID- 2263011 TI - [Effect of green tea on iron absorption in elderly patients with iron deficiency anemia]. AB - The effect of green tea on iron absorption from tablets containing sodium ferrous citrate was investigated in four elderly patients with iron deficiency anemia and in eleven normal elderly subjects. In both groups, the serum iron level reached a maximum value from 2 to 4 hours after taking iron tablets and returned to the baseline value after 24 hours. No inhibitory effect of green tea on iron absorption was recognized. PMID- 2263012 TI - [The effects of antihypertensive therapy on the aged--an intervention study in a home for the aged]. AB - Excessive antihypertensive therapy can create a risk of brain damage in the aged. Furthermore, no conclusion has been reached regarding treatment goals for systolic blood pressure (SBP). Two hundred elderly people with hypertension (SBP greater than 170 mmHg, average age 74 years) were studied, among them 40 age-sex matched pairs (80 people) were selected for further examination. They were then divided into two groups, and antihypertensive therapy was conducted on each group with systolic blood pressure level goals of 140 mmHg and 160 mmHg, respectively. To set a goal for antihypertensive therapy, we examined Hasegawa's dementia rating scale (HDS) and bilateral common carotid arterial blood flow (CCF), which were measured using the Doppler method. In the group in which the blood pressure was reduced to 160 mmHg level, changes were observed only in right CCF, and there was no change in HDS, but in the group in which the blood pressure was reduced to the 140 mmHg level, changes were observed in both bilateral CCF and HDS. It is recommended that the systolic blood pressure should be set at the 160 mmHg level to maintain the psychological function in the elderly. PMID- 2263013 TI - [Effect of aging and physical inactivity on glucose tolerance and insulin sensitivity]. AB - It has been well documented that glucose intolerance is associated with aging, but it is not yet clear whether this phenomenon is due to the aging process itself or is secondary to the appearance of other age-related conditions among which physical inactivity is one of most important variables. To evaluate the effect of aging process and/or physical inactivity on insulin action, this study was undertaken using the euglycemic insulin clamp technique and the oral glucose tolerance test (OGTT). Subjects without diabetes mellitus and other serious diseases consisted of 14 non-obese aged individuals and 10 young controls (YC group), ranging in age from 63 to 85 yrs, and from 19 to 21 yrs, respectively. The aged individuals were further divided into two groups (one was termed as the AS group, in which 7 aged subjects had been confined to bed for at least 3 months and the other was termed as the AC group in which 7 aged controls kept their daily physical activity such as walking). The results of OGTT did not show any remarkable differences between AC and YC groups. In the AS group, however, glucose intolerance and low insulin response during OGTT were observed. In view of the tissue insulin action, MCR, which is thought as a reliable marker for tissue insulin action, evaluated by euglycemic insulin clamp was 5.31 +/- 0.68, 8.57 +/- 1.20, 9.60 +/- 0.35 ml/kg/min in the AS, AC and YC groups, respectively (AS less than AC, p less than 0.05, AS less than YC, p less than 0.01, AC less than YCM, N.S.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263014 TI - [Circadian changes of blood pressure in the elderly with Alzheimer's type dementia]. AB - We evaluated the circadian changes of blood pressure in the elderly with Alzheimer's type dementia with ambulatory blood pressure monitoring (ABPM-630, Nihon Colin, Aichi, Japan). Blood pressure and heart rate were high in the daytime and low in the nighttime in the elderly without dementia. Blood pressure did not decrease in the nighttime in the elderly with dementia, although heart rate decreased. Thus, the circadian rhythm of blood pressure was selectively impaired in the elderly with Alzheimer's type dementia. PMID- 2263015 TI - [Age-related interrelation of vibration perception thresholds and somatosensory evoked potentials in normal subjects]. AB - In order to establish the age-related changes of vibration perception thresholds (VPTs) and somatosensory evoked potentials (SEPs), which are known to share a common afferent pathway in the central nervous system, 119 normal subjects ranging in age from the 20s to the 90s were studied. The VPTs of the index fingertip were measured at 63 Hz, 125 Hz and 250 Hz by a Rion vibrometer, nd the latencies of the SEPs to the median nerve stimulation (N9, N13 and N20) were simultaneously evaluated. The VPT, tended to elevate from the 40s, became increased towards higher frequencies (63 Hz less than 125 HZ less than 250 Hz) in the 80s to the 90s, whereas the VPT in younger ages showed just an opposite pattern (63 Hz greater than 125 Hz greater than 250 Hz). None of the height corrected latencies of N9, N13, N20 and central conduction time (N20-N13) revealed a significant correlation between the VPTs at any frequencies. The age related decline of vibration sense, therefore, could not be explained solely by the degenerative changes of he posterior column and/or the delay of the peripheral nerve conduction velocity. This phenomenon was rather thought to be compatible with an age-associated characteristics of Pacinian corpuscles. PMID- 2263016 TI - [Changes in the liver weight in the elderly]. AB - To elucidate the effect of aging on liver weight in the elderly, 582 elderly cases (male 291, female 291), were selected from 2000 elderly autopsied cases on the basis of being free from pathological findings affecting liver weight. Both liver weight and its ratio to body weight decreased with age, and influenced by obesity; the former increased and the latter decreased in obese cases. Analysis according to the degree of obesity also showed decrease of liver weight and is ratio to body weight with age. Comparison between males and females of the same decade revealed the tendency that in females the liver weight was low, while liver weight.body weight ratio was high. The same results were obtained by analysis based on the degree of obesity. PMID- 2263018 TI - [A clinical study of hypertrophic obstructive cardiomyopathy in the elderly]. AB - Seven elderly patients with hypertrophic obstructive cardiomyopathy (HOCM), who had the three following characteristics on echocardiograms 1) extremely thickened septum, 2) systolic anterior motion of the mitral valve, 3) mid systolic semi closure of the aortic valve, were clinically evaluated. Ages ranged from 73 to 86 years old (average 78.9% yr.) and all were women. None had not a family history of hypertrophic cardiomyopathy but they had mild hypertension. Six patients showed a significant high voltage on the ST-segment and T-wave abnormalities ("strain" pattern). The left ventricular posterior wall as well as the septum was thickened in 5 and the remaining 2 showed asymmetrical septal hypertrophy (ASH) on echocardiograms. The left ventricular cavity was narrowed due to left ventricular hypertrophy and the shape of the left ventricular cavity was ovoid in all patients. The aorto-septal angles in these 7 patients were 80 degrees to 120 degrees. In addition, proximal septal bulge in all and anterior displacement of the mitral posterior leaflet due to the mitral ring calcification (MRC) in some patients contributed to the narrowing of the left ventricular outflow tract, and the mitral valve was pulled up toward the septum because of the good left ventricular systolic function (ejection fraction: 70 to 94% by echocardiography) and blood was ejected at a high velocity through a narrowed outflow tract (Venturi effect). Pressure gradients in the left ventricular outflow tract was 38 to 146 mmHg in 5 examined by cardiac catheterization. Biopsy specimens were obtained from 2 patients, showing hypertrophic myocytes (diameter: 20 to 30 micron) in 2 and mild disarray in 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263017 TI - [Clinical characteristics of bronchial asthma in the elderly in relation to cell component in the airways]. AB - Cellular responses in the airways of bronchial asthma, which might be affected with aging, were compared between 28 elderly (60 years old or more) and 28 younger (40 years old or less) patients with bronchial asthma. The cellular responses were observed to differentiate 500 cells in bronchoalveolar lavage fluid (BALF), excluding epithelial cells. The average frequency of each type of cell in the BALF of the elderly asthmatics was 65.7% for macrophages, 15.5% for lymphocytes, 8.9% for neutrophils and 9.5% for eosinophils. In the younger asthmatics the average frequency was 61.8% for macrophages, 17.1% for lymphocytes, 4.1% for neutrophils and 16.1% for eosinophils. A significant increase in the frequency of neutrophils in BALF of the elderly cases was observed in steroid-dependent intractable asthmatics compared to the younger cases (p less than 0.05). An increase in frequency of eosinophils in the younger cases was also observed, although the difference in the frequency was not significant between the elderly and the younger intractable cases. A significant difference in the frequency of each type of cell in the clinical type of bronchial asthma was not present between the elderly and the younger cases. However, the frequency of neutrophils in elderly cases was significantly increased in Ib. bronchospasm + hypersecretion type compared to Ia. bronchospasm type (p less than 0.05), and was more elevated in II. bronchiolar obstruction type (p less than 0.01). The frequency of neutrophils was markedly more increased in the elderly cases with poor prognosis than in the younger cases (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263019 TI - [Assessment of the relation between bone mineral metabolism and mitral annular calcification or aortic valve sclerosis--the relation between mitral annular calcification and postmenopausal osteoporosis in elderly patients]. AB - We assessed the effect of bone mineral metabolism on mitral annular calcification (MAC) and aortic valve sclerosis or calcification (AVS) in elderly patients. Both MAC and AVS were derived by 2-D echocardiography, and bone mineral content (BMC) of vertebral bodies was obtained by quantitative computed tomography using a calibrated phantom system. The calcium (Ca), phosphate (P), parathyroid hormone (PTH-c), calcitonin (CLT), vitamin-D (25-(OH)D) and osteocalcin (OC) in serum were examined within a period of one month. The 265 patients were classified into three groups according to the echocardiographic findings. The control (CNT) group consisted of 122 patients (44 males, 78 females) without MAC or AVS, the MAC group consisted of 64 patients (16 males, 48 females) with MAC, and the AVS group consisted of 79 patients (31 males, 48 females) with AVS. 1) The incidences of MAC and AVS in both males and females were found to increase in proportion to aging. 2) The incidence of MAC in females (28%) was higher than that of males (18%). 3) AVS in males (34%) was more frequent than in females (27%). 4) In females of the eighth and ninth decade of age, BMC in the MAC group was significantly less than in the CNT group (eighth p less than 0.05, ninth p less than 0.01), but no difference was seen in males. 5) In both males and females, BMC in the AVS group was not significantly different from that in the CNT group. 6) In all subjects of the eighth and ninth decades, the serum levels of Ca and P were within normal ranges. PTH-c, CLT and 25-(OH)D showed subnormal or lower normal values, while OC showed supernormal or upper normal values. However, the was no difference among the three groups. These results suggest that MAC may be attributed to ectopic calcium deposit, probably related to decalcification from bone in postmenopausal osteoporosis. However, in the present study, there was no relation between the incidence of MAC and humoral factors of calcium metabolism. On the other hand, AVS may be caused by other factors, mainly prolonged and sustained pressure or stress loading. PMID- 2263020 TI - [The circadian pattern of arterial blood pressure in patients with cerebral infarction]. PMID- 2263021 TI - [The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology]. AB - Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263022 TI - [The effect of captopril on proteinuria in glomerular diseases]. AB - We evaluated the efficacy of an ACE inhibitor captopril (CAP) for the reduction of proteinuria in glomerular diseases, and tried to find the conditions in which urinary protein excretion was significantly decreased by this drug. Renin provocation test by CAP (C-test) was performed, and the result was compared to the effect on proteinuria. In 33 patients with proteinuria, ranging from 1.1 to 14.1 g/day, CAP was administered. Urinary protein excretion was reduced from 3.6 +/- 0.6 to 2.8 +/- 0.4 g/day (mean +/- SEM, p less than 0.01) after 2 weeks. The decrease in urinary protein was significant when renal function was moderately impaired (30 less than or equal to Ccr less than 60 ml/min) or patients were on a salt diet less than 7 g of NaCl daily. Reduction of urinary protein excretion by 2-week treatment of CAP was correlated with the result of C-test (r = 0.874, p less than 0.025). The long-term follow up for more than 6 months also suggested that CAP delayed the deterioration of renal function. Thus, CAP was proved effective in treating proteinuria, and C-test might give us an information of its proteinuria-suppressing effect in an individual case. But its efficacy was observed only in patients with moderately-reduced renal function or on low-salt diet. Therefore, we should select the cases carefully to expect the effect of CAP for the reduction of proteinuria. PMID- 2263023 TI - [Fluorescent chromatogram profiles of uremic hemodialyzates and cirrhosis urines]. AB - The unidentified fluorescence develop in body fluids during uremia and cirrhosis. We have used "hydrophobic" HPLC to profile these fluorescence in both 10 uremic hemodialyzates and 5 cirrhosis urines, and studied further to characterize the fluorescence and to gain more information of uremic fluorescent middle molecules. Chromatograms indicate evidently that the fluorescent substances are present in the middle molecule fraction of both hemodialyzates and urines. With reference to the chromatogram scale, the relative levels of fluorescent middle molecule in hemodialyzates were seemed 30% lower than the levels in urines, whereas the mean number of chromatogram peaks in hemodialyzates were 2-fold more than the number in urines. These unknown fluorescence have an excitation of 366 nm before and behind, and may produce more stable fluorescence of middle molecules by acid hydrolysis. These results suggest that there are possibly various modification on the uremic fluorescent substances. PMID- 2263024 TI - [Characteristics of the patients with diabetic nephropathy with relatively low serum creatinine at the initiation of dialysis]. AB - Clinical feature and creatinine metabolism were studied in 86 diabetic patients who had newly initiated dialysis treatment. In 32.5% of the patients, serum creatinine was below 8.0 mg/dl at the initiation of dialysis treatment. Gastrointestinal symptoms, general malaise, pulmonary edema and uremic encephalopathy were the causes which required dialysis treatment in those patients, and the frequency of pulmonary edema was significantly higher than in patients whose serum creatinine was above 8.0 mg/dl at the initiation of dialysis (p less than 0.05). There were no significant differences in serum urea nitrogen, potassium, sodium, albumin levels and hematocrit between low serum creatinine group (3.0-7.9 mg/dl) and high serum creatinine group (8.0-11.9 mg/dl) at the initiation of dialysis. Serum creatinine levels were highly correlated with creatinine generation rate (r = 0.788, p greater than 0.01). There was a significant correlation between creatinine generation rate and muscle volume (r = 0.863, p less than 0.001). Muscle volume of diabetic dialyzed patients was 29.5 +/- 7.0 cm3/cm in males and 26.9 +/- 5.0 cm3/cm in females, and those values were lower than those of non-diabetic dialyzed patients (p greater than 0.005). Frequency of the patients whose creatinine generation rate was below 1500 mg/day was 81.3% in diabetic hemodialyzed patients and this was significantly higher than in non-diabetic hemodialyzed patients (p less than 0.005). In conclusion, in patients with diabetic nephropathy who have to initiate dialysis treatment, uremic symptoms have progressed though serum creatinine levels are relatively low. This low serum creatinine levels in patients with diabetic end-stage renal disease are resulted from their low muscle volume. PMID- 2263025 TI - [Steroid withdrawal in renal transplant recipients]. AB - The clinically important side effects of long-term steroid use are well known. We report the results of complete steroid withdrawal in 7 living-related renal transplants in HLA-identical (3) or one-haplotype match (4) recipients initially treated with azathioprine (5) or cyclosporine (2), and steroids. After the end of the second year, steroids were stopped if renal function was normal (serum creatinine below 2.0 mg/dl) and if no alterations were seen on renal biopsy. In 1 patient steroid had to be discontinued because of the complications of steroid immunosuppression. The study population consisted of 7 patients with a mean age of 32.4 years. The sex distribution was 6 males and 1 female. All patients had received a minimum of 3 blood transfusions prior to transplantation. Steroid was discontinued 34.0 +/- 18.1 months posttransplant. Oral azathioprine or cyclosporine were employed for long-term maintenance immunosuppression. Six patients (86%) have remained continuously off steroids for 52.2 +/- 50.5 months (range 4-150) with stable renal function. The mean serum creatinine was 1.1 +/- 0.4 mg/dl at the most recent follow-up. Reinstitution of steroid was required in 1 patient (14%) for rejection (36 months after steroid withdrawal). Thus, steroid withdrawal was successful in 6 of 7 patients. In HLA-identical recipients, all are currently steroid-free. In haplo-matched patients, 75% are steroid independent. Discontinuation of steroid resulted in a decrease in serum cholesterol concentration from 246 +/- 41 to 204 +/- 25 mg/dl (P less than 0.003). We conclude that steroid withdrawal may be accomplished in selected patient without increasing the rate of graft loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263026 TI - [Prognosis of chronic glomerulonephritis--study on renal survival ratio of mesangial proliferative glomerulonephritis and membranoproliferative glomerulonephritis]. AB - Renal survival curves for the adult patients at the ages between 15 and 60 with mesangial proliferative glomerulonephritis (MesPGN, N = 366) and membranoproliferative glomerulonephritis (MPGN, N = 76) were calculated using the method designed by Kaplan and Meier. In MesPGN, 80% and 68% of the patients survived 10 and 20 years after biopsy respectively; 88% and 72% survived 10 and 20 years after apparent onset. These results were similar to those analyzed by the research team "progressive renal lesions" in Ministry of Health and Welfare, Japan. When patients were histologically divided into 4 groups according to the index of glomerular lesions, % survival in each group was reduced in relation with the severity of the glomerular lesions, and there was significant difference between renal survival curves of each 2 groups. The influence of urinary protein and hypertension at the time of biopsy on survival curves was also significant. Patients with IgA nephropathy (N = 74) showed the renal survival curve similar to those of MesPGN. The influence of hypertension on % survival was also significant in IgA nephropathy. In MPGN, 53% and 73% of patients survived 10 years after biopsy and apparent onset respectively. Therefore MPGN was poorer in prognosis than MesPGN. These results seem to be important as the controls when we try to study the long-term effects of various therapies against chronic glomerulonephritis. PMID- 2263027 TI - [Effect of superoxide dismutase on serum sickness nephritis]. AB - Antiinflammatory effect of recombinant human Cu, Zn superoxide dismutase (SOD) was studied in Wistar rats with serum sickness nephritis induced by egg albumin injection. Different dosages of SOD were given intramuscularly in nephritis rats as follows: 0 (group A), 2 (group B), 10 mg/kg/day (group C). Control rats were given 10 mg/kg/day of SOD. On day 52, histopathological examinations of the kidney were performed in all animals. Urinary albumin was 0.35 +/- 0.21, 0.24 +/- 0.14, 0.34 +/- 0.28 and 0.41 +/- 0.21 mg/day in group A, B, C and control, respectively on day 0, and 33.0 +/- 21.5, 1.52 +/- 0.54, 2.55 +/- 1.67 and 0.21 +/- 0.02 mg/day in group A, B, C and control, respectively on day 52. Daily administration of SOD significantly suppressed urinary albumin excretion (A vs B & C, P less than 0.05). Numbers of nucleus per one glomeruli in rats were 119 +/- 3.6, 76.3 +/- 6.7, 71.1 +/- 8 and 65.5 +/- 3.3 in group A, B, C and control, respectively (A vs B & C, p less than 0.01). The glomerular damage in serum sickness nephritis which was potentially induced by free oxygen radicals, would be prevented by the administration of SOD. PMID- 2263028 TI - [Ultrastructural study on membranoproliferative glomerulonephritis with special reference to subepithelial deposits]. AB - The distribution of electron dense deposits in the glomerulus was scrutinized by electron microscopy in 34 cases of membranoproliferative glomerulonephritis (MPGN). Seven cases underwent serial biopsies. Results are summarized as follows. (1) Mesangial deposits (MD) and subendothelial deposits (SEND) were demonstrated in nearly all biopsy specimens. Intramembranous deposits (IMD) and subepithelial deposits (SEPD), which had hitherto been considered uncommon in MPGN, were also seen in over three- fourths of the specimens. (2) According to these findings, Burkholder's Type III MPGN, characterized by the frequent presence of SEPD, seems not to be essential in the classification of MPGN. In contrast, Strife's type III MPGN, defined by the disruption of the glomerular basement membrane (GBM), appears to be appropriate for the classification, because the cases diagnosed as Strife's type III showed quite peculiar histology among the MPGN. (3) In most cases having undergone serial biopsies, cellular proliferation in the glomeruli was more improved at the second biopsy than at the first, which probably resulted from intensive medications such as the combined therapy of corticosteroids, immunosuppressants, and anticoagulants. On electron microscopy, however, electron dense deposits were not decreased, and SEPD was rather increased. Furthermore, the GBM was more thickened and showed more irregular structure in the second biopsy. (4) Humps were observed in 14 out of 41 biopsy specimens of MPGN. They were seen not only in the acute but also in the chronic stage of the disease, especially in the cases with persistent hypocomplementemia. These results suggest that the subepithelial deposits are more common in MPGN than considered previously, and are more closely related to the morphological changes and the progression of MPGN. In particular, humps should be a marker indicating the activity of the disease associated with hypocomplementemia, whether it is acute or chronic. PMID- 2263029 TI - [Lipid metabolism in daunomycin-induced nephrotic rats (5)]. AB - Lipid metabolism of intestine, liver and kidney was examined in daunomycin induced nephrotic rats. 1) Phospholipids, triglycerides and cholesterol contents in chylomicrons were increased in daunomycin-induced nephrotic rats. 2) Cholesterol absorption in intestine (in vivo and situ) was similar in daunomycin induced nephrotic rats and control rats. 3) Total bile acids levels in bile and portal vein were similar in two groups. 4) There was no difference in incorporation of 14C-mevalonate into cholesterol by liver and kidney slices in two groups. The oxidation of 14CO2 from 14C-mevalonate in kidney slices was decreased in daunomycin-induced nephrotic rats. These results show that the hypercholesterolemia in daunomycin-induced nephrotic rats are not caused by increased absorption of cholesterol in intestine. The increased cholesterol esters in liver are not derived from decreased bile acids catabolism. The increased cholesterogenesis in the liver of daunomycin-induced nephrotic rats may be due to an increased rate at the step prior to mevalonate. The oxidation of 14CO2 from mevalonate by shunt pathway may be decreased in the kidney of daunomycin-induced nephrotic rats. PMID- 2263030 TI - [Acute experimental uveitis caused by a single administration of heterologous blood protein to the vitreous body of rabbits]. AB - The initial allergic reaction of an uveitis character was evoked by a single application of horse's serum into the rabbit vitreous. The dynamics of the development of the inflammation was observed macro and microscopically. It was stated that there exists a close correlation of the intensification of the inflammatory reaction in the macroscopic and microscopic evaluation; the microscopic changes in the eye tissues preceded the macroscopic changes and they persisted longer. PMID- 2263031 TI - [Intraocular pressure in patients with infiltrative-edematous exophthalmos in Graves' disease treated with prednisone]. AB - Hydrodynamics of the eyes was evaluated in 29 patients in the period of one to one and a half years after completion of prednisone therapy. Open angle glaucoma was observed in 2 patients, in 3--only a raised intraocular pressure (21-25 mm Hg) in the period of exacerbation of the infiltrative changes in the tissues of the orbit. PMID- 2263032 TI - [Ocular hypertension in patients with infiltrative-edematous exophthalmos in Graves' disease]. AB - The increase of the IOP--5 to 30 mm Hg--was observed in patients in whom severe infiltrative changes in the motor muscles dominated the clinical picture. Characteristic for glaucoma changes of the visual field and optic papilla were not seen, the angle was open and the outflow coefficient was in normal limits. The normalization of the IOP was obtained after decompensation of the orbits when the exophthalmos and the infiltrative changes in the motor muscles of the eye receded. PMID- 2263033 TI - [Eye injuries in sports]. AB - On the basis of personal material from 6 years (70 patients, 104 eyes) the author discusses, the eye injuries inflicted during sport activities and their incidence in various sport disciplines. In 5-10 per cent of such injuries the final visual acuity was 0.1 or less. The possibilities of prophylaxis are also presented; suggested is the wear of protective glasses made of polycarbonate. PMID- 2263034 TI - [Congenital developmental anomalies of the visual system in children in our 13 year observations]. AB - Cases of congenital anomalies of the visual system in children hospitalized in the period 1974-1986 were analyzed. Together 305 cases were analyzed. The most frequently seen congenital anomaly was an unilateral or bilateral cataract (107 cases), further glaucoma (50 cases) and pathological changes caused by Toxoplasma Gondii (33 cases). Among principal causes of these anomalies the author ++ is citing the rubella and toxoplasmosis. PMID- 2263035 TI - [Evaluation of the effectiveness of Quinax in the prevention of the development of senile cataract]. AB - The authors evaluated the efficacy of Quinax in 4 groups of patients with cataract. An observation of--on the average--5 years duration showed that systematic application of the drug prevents the development of the early senile cataract and distinctly slows down the progress of the disease in the group of patients without the risk factors. Non systematic application of the compound also slows down the progress of the condition in the group of early cataract. The drug was ineffective in patients with an advanced diabetic cataract. PMID- 2263036 TI - [Evaluation of binocular vision in adults with strabismus treated by the localization method]. AB - The authors are continuing the work started last year and concerning the summing++ up of the results of treatment of the squint in adults according to a new classification. One hundred and sixty eight patients were subjected to the analysis; they were qualified to individual groups in dependence on the condition of their binocular vision. Six groups were separated: N--full effect, A--almost full effect, B--advanced, C--initial, D--vestigial and E--no effect. There was a larger percentage of persons effectively cured in the N-D groups in comparison with the previous year. PMID- 2263037 TI - [Relation between the position of the eyes and binocular vision in the treatment of convergent strabismus by the localization method]. AB - The diminution of the angles of squint is attained by localization exercises with hypercorrecting prisms and the straightening out of the angles by surgical procedures. The authors ++ analyzed the efficacy of the conservative and of the surgical treatment in the reduction of the deviation of the eyes in various groups of children in a different stage of cure. They stated that the best effect in the reduction of the squint may be achieved in the group of children with a good binocular vision (the group of almost full recovery) and the poorest effect- in the group of children without binocular vision. PMID- 2263038 TI - [Results of a new operation in the treatment of nystagmus]. AB - A new surgical procedure is presented (Avietisov 1978) which in contrast to the Anderson-Kestenbaum method may be used in nystagmus of every kind. The essential element of this procedure is the resection of the anterior belly of the eye muscles comprising the neuro-muscular spindles responsible for the local mechanisms regulating the action of the oculomotor muscles. Application of this method in 76 patients caused a decrease of the nystagmus amplitude in all types of this condition. The discussed operation did not however influence the frequency of the ocular movements. The performed surgical procedure lead to an improvement of the visual acuity and of the position of the head. PMID- 2263039 TI - [Improving the function of the visual system in children with aphakia]. AB - Systematic reeducation by pleoptic-orthoptic exercises was performed in children with posttraumatic and congenital aphakia for the improvement of the visual acuity, normal retinal fixation and binocular vision. The treatment comprised 244 children aged 1-16 years who were formerly given a correcting contact lens on the aphakic eye. In the result of rehabilitation a visual acuity of over 5/16 was attained in 79.5 per cent of cases, a normal retinal fixation in 73.77 per cent and the binocular vision in 46.31 p.c. Better results were obtained after treatment of a posttraumatic cataract, poorer results after extraction of a congenital cataract. PMID- 2263040 TI - [The UTAS-E1000 System in electrophysiological studies of the visual system. I. Characteristics of the system and its possibilities and equipment]. AB - The paper presents the technical and medical characteristics of the computerized system UTAS-E1000 (made by LKC, USA) destined for the electrodiagnostics of the visual system. Discussed are the properties of the construction which decide on the possibility of automatization of electrodiagnostic tests and also personal experience on the development of the system in order to increase its scope of application. PMID- 2263041 TI - [The UTAS-E1000 System in electrophysiological studies of the visual system. II. Programming and clinical use]. AB - The authors discuss a set of electrodiagnostic tests of the UTAS-E1000 system and their personal work on new tests. They present the scope of applications of the equipment in examinations of some pathological conditions of the visual system and--on the basis of their personal experience--the possibilities of introduction of new electrodiagnostic tests. PMID- 2263042 TI - [Methods of examination of the angiogenetic activity of the retina]. PMID- 2263043 TI - [Scientific report on the II Pediatric Ophthalmological Forum in Zakopane]. PMID- 2263044 TI - [Surgery of post-traumatic cysts in the iris of children]. AB - The authors describe 7 cases of implanted iris cysts which appeared after perforating corneal injuries in children aged 3 to 14 years. All the cysts have been excised by sector iridectomy performed in the healthy iris. Described is the technique of the intervention. Attention is called to the possibility of preservation of a round pupil by leaving intact the pupillary border or by a simultaneous plastic operation of the iris. PMID- 2263045 TI - [Postoperative complications with the use of implants for treatment of retinal detachment]. AB - Complications of the retinal detachment surgery with the use of episcleral and intrascleral implants are presented. The authors are using biological materials (fascia lata, dura mater) as well as alloplastic materials (Lincoff's sponge). Among the postoperative complications following were seen: protracted reactions from the side of the ocular adnexa, intraocular haemorrhages, intravitreal exudates. The most severe from the observed complications was the atrophy of the sclera at the spot of implantation of the silicon sponge. PMID- 2263046 TI - [Free cutaneous graft in reconstructive surgery of the eyelids]. AB - Surgical procedure consisting on the excision of a neoplastic, cicatrix or pigmentary change and on covering of the created defect by a free full thickness graft was carried out in 45 patients. A favourable functional and cosmetic effect was achieved in all of them. PMID- 2263047 TI - [Surgical procedure for difficult resorption of hemorrhage in the anterior eye chamber]. AB - A method of removing of blood from the anterior chamber by means of the hyaluronic acid is presented. The application of the natrium hyaluronate is raising the safety of operation as well as acts as means of protection against the appearance of intra- and postoperative complications such as secondary haemorrhages, hypotonia of the eyes or adhesions in the anterior chamber. PMID- 2263048 TI - [Physiology and function of pre-ocular tear film]. AB - Discussed are in detail the genesis and physiology of the lacrimal film and the role played by its separate layers in securing a normal functioning of the cornea, conjunctiva and the lids. Described are also the defensive mechanisms of the eye in which the lacrimal film takes also part and the role of the lids in the process of its regeneration. PMID- 2263049 TI - [Causes of disturbance in the stability of lacrimal film]. PMID- 2263050 TI - [Keratoplasty in light of many years of personal observation]. AB - Personal observation comprise 495 operations of corneal transplantation in the period of 1972-1987. The best results (80-100 per cent successes) were achieved in cases of keratoconus, Groenuow's corneal dystrophy, Salzmann's nodular degeneration, pterygium, corneal dermoid and leukoma due to viral keratitis; fewer successful results (46 p.c.) were seen in leukomas caused by corneal burn. Corneal graft rejection occurred in 67 cases (13.5 p.c.). PMID- 2263051 TI - [Compensatory head positioning as a result of ocular changes or torticollis of muscular origin in children]. AB - Presented are the causes and clinical picture of the compensatory positioning of the head arising in the consequence of ocular changes and changes in the muscles of the neck. The material was divided into 3 groups: 1) with paresis of the ocular muscles (20 cases), 2) caused by nystagmus (20 cases) and 3) torticollis of muscular origin (20 cases). The basis of the differential diagnosis of compensatory positioning of the head of ocular origin and of torticollis of muscular origin as well as the criterion of a cooperation between the ophthalmologist and the orthopaedic surgeon are delineated. PMID- 2263052 TI - [Correlation of blood flow in the posterior ciliary arteries with visual field changes and the appearance of the optic disc in patients with primary glaucoma]. AB - The velocity of blood perfusion and pulsation curve in posterior ciliary arteries was evaluated in 180 patients (476 eyes) with primary glaucoma, aged 22 to 81 years. The investigations were carried out by Doppler's focused pulsating ultrasonographic method with probes of 2 and 8 MHz frequency connected with a TC 2-64 apparatus (made by EME of German Federal Republic). The blood perfusion in the posterior ciliary arteries was compared with the changes in the visual field, in the aspect of the optic disc in patients with primary glaucoma and various levels of the IOP. In patients with primary glaucoma and advanced fundus changes (of 2-nd and 3-rd grade) the mechanisms of regulation of the ciliary circulation were normally functioning for quite a long time. In the period of breaking down of the mechanisms the changes in the visual field came into being. PMID- 2263053 TI - [Comparative evaluation of blood flow in posterior ciliary arteries in patients with glaucoma after surgical and pharmacological treatment]. AB - The perfusion of blood and pulsation curve in the posterior ciliary arteries in glaucomatous patients was evaluated before and after surgical and pharmacological treatment by Doppler's focused pulsating ultrasonographic method by means of a TC 2-64 apparatus with a probe of 8 MHz frequency. Twenty two patients were treated only conservatively, 27 by a surgical intervention. Before the installation of the treatment the intraocular pressure was higher than 35 mm Hg (averagely), the perfusion velocity was lowered and the indexes of pulsation elevated. After surgery the IOP was lowered--averagely beneath 15 mm Hg, the velocity of blood perfusion and pulsation indexes showed normal values in all the operated persons. After pharmacological treatment the IOP lowered but its mean value persisted in the 20-22 mm Hg range. Only in patients with early glaucomatous changes the blood perfusion remained normal with the intraocular pressure around 20 mm Hg. Instead in patients with advanced glaucomatous changes the velocity of the blood perfusion and the pulsation indexes showed pathological values with the IOP around 20 mm Hg. PMID- 2263054 TI - [Evaluation of methods for reproducing doppler pulsating focused ultrasonography]. AB - In 53 patients treated for primary glaucoma the authors performed 2 examinations of blood perfusion in the posterior ciliary arteries during 2 following days. The patients had been examined in the period of a normalized IOP. The difference in the IOP between the first and second examination did not exceed 3.3 mm Hg and the difference in the mean general blood pressure--10 mm Hg. The blood perfusion in the posterior ciliary arteries was checked by Doppler's pulsating focused ultrasonography, by means of a TC-2-64 apparatus with a probe of 8.0 MHz frequency. The velocity of the blood perfusion, the pulsating index and the transmission of pulsation were evaluated. The differences between respective parameters characterizing the blood perfusion in the posterior ciliary arteries between the first and second examination were statistically insignificant, on the importance level of 0.01. PMID- 2263055 TI - [Comparative investigations of changes in the ocular fundus of divers]. AB - It was established that professional divers who never suffered from decompression sickness had fundus changes similar to those changes which could be seen in divers who have had this disease. A many years diving may lead to permanent degenerative changes at the eye fundus. PMID- 2263056 TI - [The value of bezafibrate in treatment of experimental corneal herpes]. PMID- 2263057 TI - [Surgery for pterygium with transplantation of an epithelial conjunctival flap. I. Methods]. AB - Advantages and disadvantages as well as the efficacy of the most frequently applied surgical and combined methods of the pterygium therapy are discussed. A personal approach is presented; it consists of excision of the pterygium with a margin of a healthy tissue exposing the sclera and of covering of the conjunctival defect with a free epithelial layer of the bulbar conjunctiva from the upper quadrant. In case of necessity the flap may be used for a simultaneous reconstruction of the semilunar fold. The description of the method is completed by illustrations. PMID- 2263058 TI - [Surgery for pterygium with transplantation of an epithelial conjunctival flap. II. Results of methods application]. AB - The authors performed 41 operations of pterygium with transplantation of a free epithelial flap from the bulbar conjunctiva in order to cover the defect after the removal of the pathological tissue. The results of 35 operations had been controlled in the period of one to ten years. In 25 cases the operation was the first intervention, in 9 cases the second or third in a recurrent pterygium treated by other methods. In case of necessity the semilunar fold was reconstructed. A recurrence took place in one case after 6 months. The cause of the recurrence was the collection of the flap together with the fibrous layer of the conjunctiva. In the remaining cases a good and lasting effect was achieved, as well from an anatomical as from a cosmetic point of view. The results were compared with the results achieved by various authors by means of another methods. PMID- 2263059 TI - Evaluation of the Coat-A-Count 125I fentanyl RIA: comparison of 125I RIA and GC/MS-SIM for quantification of fentanyl in case urine specimens. AB - The Coat-A-Count solid phase 125I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods. The cross-reactivity with the 125I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The 125I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens. PMID- 2263060 TI - Urinary tricyclic antidepressant screening: comparison of results obtained with Abbott FPIA reagents and Syva EIA reagents. AB - Human urine was tested for tricyclic antidepressants with fluorescence polarization immunoassay (FPIA) reagents on Abbott's ADx system and with EIA reagents on Syva's ETS system. A 75-ng/mL imipramine calibrator cutoff was used with the ADx system and a 300-ng/mL nortriptyline calibrator cutoff with the ETS system. The ETS system was adapted to analyze tricyclic antidepressant (TCA) samples using the Syva Emittox serum TCA assay. Negative urine was spiked with various tricyclic and tetracyclic antidepressants, phenothiazines, and other medications with potential to interfere with the assays. Verification of samples was performed by thin-layer chromatography and gas chromatography/mass spectrometry. The different compounds were added to urine at concentrations of 200, 400 and 1,000 ng/mL. At 1,000 ng/mL all TCA compounds tested gave positive results with the ADx and ETS systems. However, some non-TCA medications spiked at 1,000 ng/mL gave false positive results with both systems. The tetracyclic antidepressants did not cross-react and gave negative results. Clomipramine spiked urine at 400 ng/mL yielded a false negative result on the ETS system. PMID- 2263061 TI - Automated rule-based decision systems in forensic toxicology using expert knowledge: basic principles and practical applications. AB - This paper presents the basic principles and practical benefits of the application of expert systems (ES) and artificial intelligence (AI) to problem solving in forensic toxicology. We acknowledge the complexity and elegance of the theoretical substance and program algorithms of existing work in these disciplines, while simultaneously observing that many presentations of this material cloak the essential facts and concepts in unnecessary jargon and hyperbole. We attempt to remove the cloak without misrepresenting or oversimplifying the underlying structures. We first present a summary of the history, basic functions, technical fundamentals, and typical applications in three major categories of established ES/AI systems. We then assess the status of ES/AI in the forensic toxicology laboratory (FTL) with emphasis on potential applications. We conclude with an analysis of experiences with ESs in our laboratory where we have used an integrated expert system to reduce laboratory errors, detect internal inconsistencies in data, discover new substance abuse subpopulations, and reduce the frequency of sample reprocessing. We have minimized specimen processing time and instrument wear while maximizing technician efficiency and thus performing more tests for the same or reduced costs. PMID- 2263062 TI - Determination of lysergic acid diethylamide (LSD) in urine by instrumental high performance thin-layer chromatography. AB - An instrumental high-performance thin-layer chromatographic (HPTLC) technique for the determination of lysergic acid diethylamide (LSD) in urine was developed. Before chromatographic separation, a single-step extraction with alkaline wash is performed. The procedure can detect less than 1 microgram LSD/L urine. Results of HPTLC determination are compared with those from a radioimmunoassay (RIA) procedure. PMID- 2263063 TI - Direct automated EMIT d.a.u. analysis of N,N-dimethylformamide-modified serum, plasma, and postmortem blood for amphetamines, barbiturates, methadone, methaqualone, phencyclidine, and propoxyphene. AB - The addition of two volumes of N,N-dimethylformamide (DMF) to serum, plasma, and postmortem blood with subsequent centrifugation resulted in supernatant that could be directly analyzed by EMIT d.a.u. urine reagents on the Syva autocarousel. Application of this method to the drugs below gave cutoff concentrations in milligrams of immunochemically cross-reactive analyte equivalents/L as follows: 0.05 for amphetamine, 0.05 for secobarbital, 0.075 for methadone, 0.05 for methaqualone, 0.025 for phencyclidine, and 0.05 for propoxyphene. Quantitative "false" negative/positive noncongruence between total EMIT cross-reactants and free-drug analyses by gas chromatography/mass spectrometry were 3/4 (n = 50) for amphetamines, 2/0 (n = 60) for barbiturates, 0/0 (n = 47) for methadone, 0/0 (n = 48) for methaqualone, 1/0 (n = 44) for phencyclidine, and 1/2 for propoxyphene (n = 53). Within-day precision, as indicated by the coefficient of variation, of quantitative estimates using low and high controls ranged from 3.7 to 11% and 1.8 to 10.3%, respectively. Using the same control levels, between-day precision of quantitative estimates varied from 5.8 to 30.3% and 3.0 to 11.8%, respectively. PMID- 2263064 TI - Determination of chlorinated hydrocarbon pesticides by solid-phase extraction and capillary GC with electron capture detection. AB - Pesticides and their metabolites are extracted and concentrated from serum using C18 solid-phase extraction cartridges. The internal standard aldrin is added to 4 mL of serum or plasma, treated with 2 mL of methanol, and the resultant supernatant applied to the C18 cartridge. After several washes, pesticides are eluted from the column with isoctane and the eluate quantified with capillary gas chromatography using electron capture detection. Extraction efficiency is from 70 to 75% and the method detection limit ranges from 0.1-0.7 ng/mL depending on the analyte. Precision studies demonstrate that CVs range from 3.5 to 25.2%. Standard curves are linear to at least 7 ng/mL for lindane and chlordane isomers, heptachlor, heptachlor epoxide, oxychlordane, trans-nonachlor, dieldrin, dichlorodiphenyldichloroethylene (p,p'-DDE), dichlorodiphenyldichloroethane (p,p' DDD), and dichlorodiphenyltrichloroethylene (p,p'-DDT). PMID- 2263065 TI - Vitreous humor in the evaluation of postmortem blood ethanol concentrations. AB - Many studies have been published comparing blood (B) ethanol (EtOH) and vitreous humor (VH) EtOH concentrations. We conducted a similar study of routinely collected specimens to determine (1) whether the reported average VH/B ratios are consistent, (2) the percentage of cases with VH/B ratios outside of the expected range, and (3) the magnitude of B EtOH that can be associated with negative VH EtOH (less than 0.01 g/dL). VH EtOH less than 0.01 g/dL was associated with 41 specimens; 34 specimens had B EtOH less than 0.03 g/dL while a B EtOH as high as 0.12 g/dL was measured. For B EtOH less than 0.10 g/dL, 67% had VH EtOH within 0.02 g/dL of B EtOH (N = 101). For B EtOH greater than or equal to 0.10 g/dL, the VH/B EtOH ratio ranged from 0.10 to 1.91; the mean ratio was 1.17 and the median ratio was 1.18 (N = 205); and 64% had a ratio between 1.00 and 1.39. Vitreous humor can be used to facilitate understanding the significance of postmortem blood EtOH concentrations. PMID- 2263066 TI - Poppy seed ingestion and opiates urinalysis: a closer look. AB - Review of scientific literature shows that ingestion of poppy seed containing products can result in a positive urinalysis test for opiates. In many cases the amount of seeds ingested is unrealistically high or is not specified. This study is designed to correlate the amount of seeds ingested with the urinary concentration of total morphine as a function of time. Two males and two females were involved in all four protocols, which were separated by at least one week. Subjects ingested one, two, or three poppy seed rolls, each containing 2 g of Australian seeds (108 micrograms morphine/g seed) in three protocols. In the fourth protocol subjects ingested two rolls per day for four consecutive days. Urine specimens were collected for 48 h after ingestion, analyzed by RIA, EMIT, and TDx, and selected samples were confirmed by GC/MS. The data show that the highest concentrations of total morphine in urine were found 3-8 h after ingestion or in the first-void samples. Of the 264 samples collected, there were only 16 specimens that exceeded 300 ng/mL by any of the methods used for analysis with only three samples exceeding 400 ng/mL by GC/MS (406, 611, and 954 ng/mL). In all cases, the total opiates level was less than 150 ng/mL 24 h after ingestion. Following these studies, one of the subjects ingested a poppy seed cake containing 15 g seed obtained from a bakery which analyzed for 169 micrograms morphine/g seed. Urine specimens were collected over 48 h, and all specimens were analyzed by GC/MS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263067 TI - Quinidine inhibits in vivo metabolism of amphetamine in rats: impact upon correlation between GC/MS and immunoassay findings in rat urine. AB - Amphetamine is metabolized by cytochrome P-450 (P450) to p-hydroxyamphetamine and phenylacetone in mammalian species. P450 metabolism is affected by genetic polymorphisms and by xenobiotic interactions in an isozyme-specific fashion. Little is known concerning the isozyme selectivity of amphetamine metabolism. Quinidine selectively inhibits the debrisoquine-specific isozyme (P450db) which displays genetic polymorphism in humans and rats. We now report the effect of quinidine on the metabolism of amphetamine to p-hydroxyamphetamine in vivo. At 0 h male Lewis rats received (po): no treatment (I), 80 mg quinidine/kg in 50% ethanol (II), or 50% ethanol (III), followed at 2 h by 15 mg d-amphetamine sulfate/kg (po). Urine specimens were collected and pooled at 0, 24, and 48 h. Amphetamine and p-hydroxyamphetamine concentrations were determined using a new GC/MS method for simultaneous quantitation. The ethanol vehicle-control (III) had no significant effect on amphetamine metabolism. Quinidine pretreatment (II) resulted in a significant decrease in the excretion of p-hydroxyamphetamine at 24 and 48 h to 7.2 and 24.1% of the vehicle-control levels, respectively, accompanied by a significant increase in amphetamine excretion between 24 and 48 h to 542% of the control. These data show that quinidine inhibits in vivo metabolism of amphetamine in rats and suggest that amphetamine metabolism may, in part, be mediated by an isozyme of P450 which displays genetic polymorphism. The inhibition of amphetamine metabolism results in an increased ratio of parent drug to metabolite concentration (metabolic ratio) in the urine, which mimics the effect of genetic polymorphisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263069 TI - Determining the temperature of injection ports, GC ovens, and temperature ramps in GC/MS systems. AB - This note presents a procedure for determining the temperature of Hewlett-Packard GC/MS systems by assigning a voltage signal to the injection port and oven and monitoring the signal output. The signal counts are then coverted to temperature by a calculation. PMID- 2263068 TI - Whole blood quality assurance control samples for forensic toxicology. AB - Pilot studies were undertaken to examine the feasibility of preparing freeze dried whole blood samples containing drugs of interest to be used as assay controls. The availability of such samples will enable analysts and laboratory managers to monitor analytical performance. A pilot batch of freeze-dried blood containing five compounds of forensic significance and a blank blood sample were prepared for reconstitution to 2.5-mL aliquots. Samples of each of these preparations were distributed to 55 laboratories in the USA and UK for analysis. A summary of the results is presented along with comments on the feasibility of producing freeze-dried whole blood samples for use in forensic toxicology. PMID- 2263070 TI - The production of amitriptyline from nortriptyline in formaldehyde-containing solutions. AB - The stability of nortriptyline in aqueous solutions containing various concentrations of formaldehyde was investigated. Amitriptyline, as a reaction product, was determined by gas chromatography/mass spectrometry (GC/MS) in these experiments. Factors that may contribute to this phenomenon, including pH, formaldehyde concentration, and incubation time were evaluated. At 40% (v/v) formaldehyde concentration and pH 4, there was a 68% decrease in nortriptyline concentration along with a concomitant formation of amitriptyline after 24 h. The N-methylated product was responsible for 48% of the total tricyclic drug present. The data also clearly indicate that the formation of amitriptyline is favored at elevated pH. PMID- 2263071 TI - Report of a fluoxetine fatality. AB - Several fatalities due to fluoxetine combined with other drugs such as ethyl alcohol have been reported. We now report an apparent suicide in which fluoxetine was the only causative agent. Because this drug is widely described as having a wide safety margin, it is important to note concentrations in blood associated with overdose fatalities. The findings by GC/NPD and GC/MS in blood were as follows: fluoxetine 6,000 ng and demethylated metabolite 5,000 ng/mL. Parent compound and metabolite were 13,000 ng/mL each in bile. Details of the analytical method and data from 2,100 National Medical Services cases are also presented. PMID- 2263072 TI - Carisoprodol concentrations from different anatomical sites: three overdose cases. AB - Three cases involving overdoses of carisoprodol are presented. Concentrations of carisoprodol and its major metabolite meprobamate, were determined in urine, vitreous humor, heart, and femoral blood. All drugs were quantified by gas chromatography/mass spectrometry (GC/MS). PMID- 2263073 TI - Audit and son...? PMID- 2263074 TI - The transfer of hazardous industries. PMID- 2263075 TI - Research in occupational health. Engineering industry perspective. AB - Predicting the research needs within the engineering industry over the next 10 years requires a clear view of the industry's priorities and the role of the Occupational Health Practitioner in a rapidly changing and demanding world. This article describes the possible impact of manufacturing and social trends on occupational health practice and proposes priorities which favour operational requirements over fundamental scientific need. PMID- 2263076 TI - Needs of occupational health practitioners: industrial priorities in next 10 years in transport. AB - The operational structure of public transport will not change within the next ten years. The need is demonstrated for research to help improve the working environment, eliminate hazards and enable more effective deployment of staff to meet increasing demand on the industry. PMID- 2263077 TI - Safety at work for railway staff in Britain. AB - The recent series of railway accidents raised questions about the safety of British Railways. We have studied trends in accidents to railway staff over a 33 year period, 1954-86, which time has covered the pre- and post-modernization of the railways, in conjunction with large reductions in both staffing and traffic volume. The Railway Inspectorate, which has the duty of investigating and reporting on accidents occurring on railway premises, defines three kinds of accident: train, movement and non-movement. The numbers of railway staff killed and injured in each kind of accident have been studied in relation to the number of staff employed and train-miles run. Trends in the three accident rates derived thereby show quite different patterns: for most of the period under study, train accident rates have shown a linear increase and movement accident rates a linear decrease, whilst non-movement accidents exhibited no particular trend at all. In the last 5 years, however, both movement and non-movement accident rates have decreased sharply, whilst train accident rates have increased above the generally rising trend. Explanations for some of these trends and changes are suggested, but the reasons for others remain obscure. PMID- 2263078 TI - An evaluation of undergraduate occupational health teaching. AB - It has been reported that at present, UK medical schools do not have a uniform approach to undergraduate occupational health teaching. Consequently, a suggested educational framework for this teaching has been prepared. In this study a problem management questionnaire was used to evaluate a course based on this framework. Patterns of student understanding about hazards, risk groups, and staff responsible for occupational health in the hospital environment, were compared before and after the courses. This environment was chosen for study because after graduation all doctors work for some time in hospitals and different doctors may treat hospital staff for problems acquired at work. The findings show that although specific teaching of hospital occupational health is not given, students grasp the introductory concepts and then modify their approaches to the prevention and clinical care of health problems associated with hospital employment. In particular, they become more aware of different risk groups and the sources of professional advice. Findings from such studies before and after tuition, help tutors to identify gaps in knowledge and can be used with student groups to reinforce their interest in learning. PMID- 2263079 TI - The application of a short anxiety and depression questionnaire to oil industry staff. AB - A short anxiety and depression questionnaire developed by Goldberg et al. was applied to 796 employees of an oil company operating offshore in the North Sea. Anxiety and depression scores were compared in offshore staff and their onshore counterparts at different levels of seniority. These scores were taken to be indicators of stress levels. No statistically significant differences in anxiety or depression scores were identified between groups working onshore or offshore. PMID- 2263080 TI - A survey of the dental health of the workers on two groups of offshore installations. AB - The study of the medical evacuation records from offshore installation workers indicated that dental pathology may be a significant problem. This investigation was set up to gather more accurate information. The intention was to examine the mouths of as many of the workforce as possible. This covered both day and night shifts and both tours of duty. The examinees numbered 493 out of an offshore population of 967. Half of the examinees attended the dentist regularly. Eight per cent of those examined had been evacuated for dental reasons. Thirty-six per cent were in the authors' high or medium occupational risk groups. There are opportunities for action to be taken to improve the situation. PMID- 2263081 TI - Occupational diseases of teeth. AB - Occupational diseases of the teeth have, in general, received scant attention. The chief cause of this is lack of awareness among occupational physicians. Exposure to various chemical substances is one of the causes of occupation related dental disorders. Physical and biological factors also contribute. The combination of these factors plus poor dental hygiene aggravates the condition. The present article aims to focus the attention of occupational physicians towards this important problem. PMID- 2263082 TI - Hypothyroidism in textile workers. AB - Four cases of overt hypothyroidism, three of whom were men in their early forties, had occurred over a period of 6 years at a textile factory where thiourea and resorcinol were used in the finishing departments. A follow-up survey of 189 men and 48 women (44 per cent of employees) revealed 12 new cases of varying grades of hypothyroidism, categorized after the system proposed by Evered. These included a case of mild hypothyroidism in a male worker, who subsequently received thyroid hormone replacement therapy as a hospital out patient. A full occupational hygiene survey was carried out to determine possible sources of exposure to thiourea and resorcinol. Although we were unable to demonstrate a statistically significant occurrence of biochemically and immunologically detectable disturbances in thyroid function among this workforce, we did note that three of the original index cases and several of those workers with varying degrees of minor dysfunction in the follow-up study seemed to cluster in locations where exhausted fumes could accumulate. PMID- 2263083 TI - Aerodynamic evaluation of crystalloid and colloid flush perfusion for lung preservation. AB - To assess the effectiveness of pulmonary perfusion we evaluated the lung mechanics of 36 canine lungs in an isolated perfused working lung (IPWL) model. Four groups of lungs (n = 9 each) were preserved by pulmonary artery flushing with either high-potassium colloid (UW), high-potassium crystalloid (EuroCollins', EC), low-potassium crystalloid control (lactate), or low-potassium substrate-enhanced crystalloid (RPMI) followed by 130 +/- 10 min of cold storage. Ventilation remained constant (TV 10 ml/kg at 14 breaths/min with 5 cm H2O PEEP). Assessed data included lung resistance (R), timed expiratory volume (EV0.3 sec as %TV), lung compliance (C), elastic work (Wel), and flow-resistive work (Wres). Immediately following storage, R and Wel were similar for all groups (16 +/- 3 cm H2O/liter/sec and 149 +/- 18 gm/min). UW preserved lungs were less compliant (1.5 +/- 0.1 X 10(-2) liter/cm H2O) and required more inspiratory work (Wres 5.8 +/- 0.8 gm/min) compared to the low-potassium crystalloid (Lactate) group (2.0 +/- 0.1 X 10(-2) liter/cm H2O and 3.4 +/- 0.6 gm/min, respectively, P less than 0.05). For 3 hr of reperfusion, crystalloid lungs showed no significant change in R, C, Wel, or Wres. In contrast, R of the UW group increased significantly to 32 +/- 5 and 40 +/- 8 cmH2O/liter/sec at 1 and 3 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263084 TI - Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome. AB - The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies. PMID- 2263085 TI - Postischemic renal dysfunction: the limited role of xanthine oxidase-generated oxygen free radicals. AB - Oxygen free radicals (OFRs) generated during reperfusion are putative mediators of postischemic renal dysfunction. To address this issue, the renal response to ischemia and reperfusion was compared to the response to OFR generation without ischemia. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with an asanguinous modified Krebs' buffer. Kidneys were subjected to 30 min of ischemia followed by reperfusion or to OFRs generated by combining 25 mumole hypoxanthine with 1 unit xanthine oxidase. Both insults caused a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and an 80% reduction in glomerular filtration and urine flow rates. The OFR scavengers, superoxide dismutase (SOD, 250 units/ml) and catalase (CAT, 500 units/ml), prevented these alterations after OFR generation but not after 30 min of ischemia and reperfusion. SOD and CAT also afforded no protection against the less severe dysfunction observed after 10 or 20 min of ischemia and reperfusion. OFRs do not appear to be prominent mediators of postischemic renal dysfunction; other factors, probably associated with ischemia must be primarily responsible. PMID- 2263086 TI - The postprandial circulatory and ileal intraluminal release of neuropeptide Y in conscious dogs. AB - Neuropeptide Y (NPY), a 36-amino-acid peptide, was measured in the peripheral circulation and ileal lumen of conscious dogs using a sensitive radioimmunoassay. Fasting NPY concentrations averaged 448 +/- 15 pg/ml in the peripheral blood and 364 +/- 23 pg/ml in the ileal effluent. Following a mixed meal, circulating NPY levels rose to 499 +/- 37 pg/ml (P less than 0.05), whereas recoverable quantities of ileal intraluminal NPY fell to 257 +/- 19 pg/ml (P less than 0.05). Neither fat nor glucose meals significantly changed circulating or ileal intraluminal NPY recovery. These results demonstrate release of NPY into the blood and ileal lumen for the first time and support NPY as a candidate gut hormone. PMID- 2263087 TI - Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose. AB - Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods. PMID- 2263088 TI - Does glucagon improve the viability of ischemic intestine? AB - The effects of glucagon, heparin, urokinase, thromboxane synthetase inhibitor (OKY-046), and the free radical scavengers, superoxide dismutase and catalase (SOD + CAT), on the viability of ischemic intestine were evaluated based on various parameters measured. The mucosal blood flow, the fluorescence pattern, and the histopathological findings in a rabbit model with 3.5 hr total vascular occlusion of a short small intestine indicated that glucagon improved the ischemic intestine. Glucagon increased, tremendously, the mucosal blood flow by 112% in the ischemic intestine compared with that of 25% in the nonischemic intestine. This indicated that vascular spasm, not reperfusion injury or thrombosis, played the initial role in the progression of transmural bowel necrosis. In addition, the outcome in the viability of the ischemic intestine was not detected by the fluorescence technique but was able to be detected through the mitochondrial morphology under the electron microscope. PMID- 2263089 TI - [Zosteriform eruption in a girl during resolution of varicella]. AB - We show the case of a six-years-old little girl with a herpes zoster which appeared while a varicella was resolving. We are discussing the diagnosis difficulties of this process. PMID- 2263091 TI - [Intranasal trichofolliculoma]. AB - Trichofolliculoma is a rare benign neoplasm originated from hair follicle. Although this tumor often shows a suggestive clinical appearance, an accurate diagnosis only can be established by histopathologic findings. We report a case of intranasal trichofolliculoma. To the best of our knowledge, trichofolliculoma has not been previously described in this location. PMID- 2263090 TI - [Acute neutrophilic febrile dermatosis (Sweet syndrome) associated with melanoma]. AB - A 45-years-old woman affected of Acute febrile neutrophilic syndrome is presented, with no reliable etiology. In a rutinary control, a pigmented ledion of one year of evolution was observed and a surgical excision was performed, with histological diagnosis of spreading superficial melanoma. In the next weeks of post-operatory, the Sweet's syndrome was decreased, disappearing completely two months later. No recurrences of Sweet's syndrome or malignant melanoma were observed after two years of follow-up. Association between Sweet's syndrome and neoplasias, in particular solid tumors, is commented, and the literature is reviewed. PMID- 2263092 TI - [Systemic mastocytosis]. AB - We record a case of systemic mastocytosis in a 70 year old male whose clinical picture started with abdominal symptomatology (pain and diarrhea) and syncopal episodes, who was found to have hepatosplenomegaly and skin, bone and bone-marrow involvement. Papulo-erythematous lesions appeared over the scar tissue of a previous colyscectomy. Scratching of these lesions produced urtication. Histologically an infiltration of mastocytes was found, being compatible with the diagnosis of systemic mastocytosis with Koebner's phenomenon. We review the most remarkable characteristics of systemic mastocytosis. PMID- 2263093 TI - [Fibrous hamartoma in childhood]. AB - A new case of fibrous hamartoma of infancy is described as a benign but persistent soft-tissue tumor that appears during the first 2 years of life, as a rare condition. The histopathological study shows the three characteristic elements: fibrous, uni-locular adipose tissue and mixoid mesenchymal tissue. The histogenesis of this peculiar tumor is discussed. PMID- 2263094 TI - [Vasculitic urticaria: study of 12 cases]. AB - Twelve cases of chronic urticaria with histopathologic features of lecocitoclastic allergic angitis are studied. The type of cutaneous lesion, personal and familiar atopic history and the presence of autoimmune disease are described. Light microscopy, direct immunofluorescence, anti DNA, antinuclear, antithyroid, Ro, La, Rnp and Sm antibodies, total complement levels, C3 and C4, rheumatoid factor, latex, ASTO, cryoglobulines and complete workup were investigated, taking into account natural progression and response to therapy. Two different groups are defined: 1) normocomplementemic (5 patients) and 2) hypocomplementemic (7 patients). They were all women except one. The cutaneous lesions were indistinguishable in the two groups. Only in the second group there was an associated disease (systemic lupus erythematosus, Sjogren syndrome disease, lupus-Sjogren overlap, autoimmune thyroid disease). Urticaria had been present from the onset of the disease in 4 patients, and occurred later during its course in 8 others. Five patients had thyroid disease (Hashimoto thyroiditis or Graves disease), two of them being mother and daughter. Another patient had a family history of Grave's disease and urticaria. Anti DNA antibodies were found in 7 cases, and anti Ro + La + in 3 cases. Response to treatment was variable with spontaneous cycles of worsening and remissions. One of the patients found a relationship with certain foods. Histopathologic results are related in both clinical normocomplementemic and hypocomplementemic groups. No significant differences were found between the two groups, but Ro+ and La+ patients exhibit more intense cariorexis and neutrophilic infiltrates. PMID- 2263095 TI - [Metastatic alopecia]. AB - Two cases of metastasic alopecia from breast adenocarcinoma were reported. Clinical and differential aspects from other types of alopecia are also commented. PMID- 2263096 TI - [Dyshidrosiform pemphigoid]. AB - We report herein a new case of dyshidrosiform pemphigoid. Although vesiculo bullae on palms or soles are frequent components of bullous pemphigoid, they are rare as a presenting phenomenon. In our opinion, dyshidrosiform pemphigoid should not be regarded as a distinctive form of localized pemphigoid. PMID- 2263097 TI - [Epithelioid sarcoma. Immunohistochemical study. Therapy with recombinant alfa interferon]. AB - A case of Epithelioid Sarcoma in a 26 years old woman is reported. Clinical aspects of this entity are commented. Immunomarcation with monoclonal and policlonal antibodies was made, the findings were compared to those of the literature. Supervivence of the patient for 6 years without agressive surgery is remarked. Treatment was ruled out with recombinant alfa interferon for the last 3 years. PMID- 2263098 TI - [Facial granuloma caused by cactus bristles]. AB - We report a 39 year old female, who 6 years later of accidental injury with cactus bristles, developed granulomatous lesions in her face with an ulcerative tendency. Histopathologic picture showed granulomatous infiltrates filling the full-thickness of the dermis, with abundant number of multinuclead giant cells foreign-body-type and Langhans-type and mixed inflamatory infiltrate. In the dermo-hipodermal limit, several foreing bodies were found with a thorny or barb shape, some of them into the giant cells, with were PAS positive and showed a brilliant refractile aspect under polaroscopic examination. PMID- 2263099 TI - [Eosinophilic ulcer of the tongue. Pathogenic role of eosinophils]. AB - A male patient with an ulcerative lesion on the edge of his tongue is present. The histopathologic findings were typical for "Eosinophilic Ulcer of the Tongue". This was contiguous with a carious molar, the remotion of which was followed by total remission of the ulcer. Its possible aetiology and pathogenesis are discussed. Based on the injurious effects of eosinophils mentioned in anothers affections the authors postulate that eosinophils may have an important rol in production or maintainance of this ulcer. PMID- 2263100 TI - [Acquired bullous epidermolysis and multiple myeloma]. AB - A case of epidermolysis bullosa acquisita (EBA) with negative direct immunofluorescence and multiple myeloma is reported. Epidermolysis bullosa acquisita has been associated with several systemic diseases, but only three cases diagnosed of EBA have been associated with multiple myeloma in the literature. PMID- 2263101 TI - [Attitude of the students to forensic medicine]. PMID- 2263102 TI - [Follow-up of children with renal injuries: long-term prognosis can not be assessed before the patients reach adult age]. PMID- 2263103 TI - [A training program after coronary surgery improves blood lipid profile]. PMID- 2263104 TI - [Psychiatry must offer a qualified ambulatory care to the elderly]. PMID- 2263105 TI - [Infravesical obstruction can be treated with a prostatic spiral]. PMID- 2263106 TI - [Lateral spinal stenosis and lateral recess syndrome--well-known diagnoses?]. PMID- 2263107 TI - [Global prevention of HIV infection. Steady sexual relations mean safe protection. Use of condoms is like Russian roulette]. PMID- 2263108 TI - [The HELLP syndrome, a treacherous condition which can complicate late pregnancy]. PMID- 2263109 TI - [Anti-angina therapy can cause false negative exercise test]. PMID- 2263110 TI - [Magnetic resonance tomography. Asthma turned out to be aortic malformation]. PMID- 2263111 TI - [High competence, making priorities, early intervention are important parts in future ambulance care]. PMID- 2263112 TI - [Occupational and environmental medicine in Estonia--a field for further cooperation]. PMID- 2263113 TI - [Toward safer sex--is it possible to influence the sexual habits of Swedes?]. PMID- 2263114 TI - [The laser theory is not the same as the reality]. PMID- 2263115 TI - [Wall to wall carpets--a risk of allergy for some individuals]. PMID- 2263116 TI - [It is absurd to treat schizophrenia with abreaction]. PMID- 2263117 TI - [Can myopia be treated with laser?]. PMID- 2263118 TI - [Sexual contact patterns are of significance for the epidemiology of sexually transmitted diseases]. PMID- 2263119 TI - [HIV-infected women and their children: the situation of transmission and care]. PMID- 2263120 TI - [The HIV/AIDS department in the Soder hospital--a nursing experiment. A unique care environment for better care of patients with AIDS]. PMID- 2263121 TI - [Lower urinary tract problems in women]. PMID- 2263122 TI - [Bladder catarrh--not only bacterial cystitis]. PMID- 2263123 TI - [The technique of specimen collection is significant for the result of analysis of capillary specimens in primary health care]. PMID- 2263124 TI - [In spite of the statistics from the National Board of Health and Welfare: congential deformities are not more frequent in the municipality of Malmo than in the rest of the country]. PMID- 2263125 TI - [A check list for diagnosis and basic investigation of dementia in primary health care]. PMID- 2263126 TI - [Compulsory priorities in health care: knowledge and ethical analysis are needed for decisions about who will be favoured and who will not]. PMID- 2263127 TI - [Priorities in psychiatric care--a process based on arbitrary decisions of professionals?]. PMID- 2263128 TI - [Clinical pharmacology will be a specialty in the USA]. PMID- 2263129 TI - [Helicopters of the Swedish Department of Defense--a limited resource]. PMID- 2263130 TI - [Andrology--surgical aspects]. PMID- 2263131 TI - [Andrology--medical aspects]. PMID- 2263132 TI - [Transoral surgery of the upper cervical spine. Hazardous and seldom necessary]. PMID- 2263133 TI - [Delayed introduction of gluten in the diet is a possible cause of increased incidence of celiac disease]. PMID- 2263134 TI - [Assisted fertilization in involuntary sterility. A consensus panel: we have considered the facts presented by the experts]. PMID- 2263135 TI - [The debate of Miraxid: preparations in demand without side-effects]. PMID- 2263136 TI - [How to interpret information on antibiotics with pivalin acid?]. PMID- 2263137 TI - [Low number of abortions depends on values and social pressure]. PMID- 2263138 TI - [Using tape for the correction of certain ear deformities in newborn infants gives at least as good results as a later surgery]. PMID- 2263139 TI - [HIV-1 infection and nervous system symptoms--the diagnosis of dementia is misused]. PMID- 2263140 TI - [Reconstructive surgery after tetraplegia. Improving methods for the rehabilitation of arm and hand functions in patients with tetraplegia]. PMID- 2263141 TI - [Paracrine control of testicular function--a rapidly growing research field]. PMID- 2263142 TI - [Possibility of treating male infertility with pulsatile GnRH administration]. PMID- 2263143 TI - [Chlamydia conjunctivitis is a condition often misdiagnosed]. PMID- 2263144 TI - [Active euthanasia in The Netherlands--sharp internal criticism is discovered]. PMID- 2263145 TI - [Psychosocial gynecology and obstetrics: advice and prescriptions are not always necessary--to listen can be enough]. PMID- 2263146 TI - [Too restrictive hormonal substitution during and after climacteric]. PMID- 2263147 TI - [Increased use of estriol treatment of elderly women decreases the costs to society]. PMID- 2263148 TI - [A consensus statement: treatment of cancer with antineoplastic agents]. PMID- 2263149 TI - Application of pulsed and continuous wave 1.32 and 1.06 microns wavelengths of the Nd:YAG laser in the canine tracheobronchial tree: a comparative study. AB - Previous investigations have shown good clinical potential for the use of the 1.32 microns wavelength Nd:YAG laser because its soft tissue absorption is better than that of the 1.06 microns wavelength Nd:YAG laser. The 1.32 microns wavelength Nd:YAG laser has an absorption coefficient in water that is 10 times higher than the 1.06 microns wavelength Nd:YAG laser. A comparative in vivo study of laser soft tissue effects was performed by using the 1.32 microns wavelength and the 1.06 microns wavelength Nd:YAG lasers in a pulsed wave (PW) mode and continuous wave (CW) mode using a non-contact endoscopic delivery system. A standard 5 mm mucosal lesion was made in the canine tracheobronchial tree down to the level of the perichondrium. Soft tissue and cartilage effects were examined by light and scanning electron microscopy, acutely, 1 week and 2 weeks after operation, and a comparison was made between the different laser modalities. To create similar lesions, higher energy was required when using the 1.06 microns wavelength Nd:YAG laser. Soft tissue injury was greater with the 1.06 microns wavelength in CW mode, and no cartilage damage occurred in the PW mode. Soft tissue and cartilage repair after 1 and 2 weeks was better with the 1.32 microns wavelength laser. In comparison, the CO2 laser and the contact Nd:YAG laser proved to be more precise cutting tools than the 1.32 microns wavelength or the 1.06 microns wavelength Nd:YAG lasers. Both Nd:YAG laser wavelengths were useful for coagulation and vaporization of tissues and blood vessels. More studies are needed to determine the effect of the new 1.32 microns wavelengths on endotracheal tumors. PMID- 2263150 TI - Limitations of a thermal camera in measuring surface temperature of laser irradiated tissues. AB - Thermal cameras are used in research laboratories to measure tissue temperature during laser irradiation. This study was an evaluation of the accuracy of a 3-5 microns thermal camera and two 8-12 microns cameras in detecting the maximum temperatures of small targets. The size of the targets was within the range of laser spot diameters which are used for vessel welding, angioplasty, and dermatology. The response to a sharp thermal edge was measured and analyzed for the three cameras, which had a scanning rate of 30 frames per second. The response of the 3-5 microns camera to reference black body targets of different sizes was also studied. It was found that the detector system required an average of 2.44 microseconds to reach 90% of maximum step response for the 8-12 microns system and 5.85 microseconds for the 3-5 microns system. With a 3 x telescope and a 9.5 inch focal distance close-up lens, the 3-5 microns camera underestimated the temperature of targets smaller than 2.0 mm because of its slow detector response. Although the 8-12 microns camera provides more accurate measurements due to its faster detector response, it still underestimates the temperature of targets smaller than 900 microns, when similar magnification and focal distance are used. Methods to compensate for the inaccuracies are discussed, including empirical correction factors and the inverse filtering technique. PMID- 2263151 TI - Laser-irradiation-induced relaxation of blood vessels in vivo. AB - The response of blood vessels to laser irradiation in vivo was studied in the dorsal skin flap glass window chamber model of hamsters. The vasodilatory response of venules was critically dependent on the wavelength of irradiating laser. Relaxation was not produced in arterioles, although it was tried repeatedly. Vessels were irradiated with the 514.5 nm single line argon laser with irradiances from 1 to 10 W/cm2 on a 1.2 mm-diameter spot. Irradiation of venules with 2.2 W/cm2 and 4.25 W/cm2 produced reversible relaxation. Venules relaxed initially and after the interruption of irradiation returned to their original diameter. At higher irradiances (8.5 W/cm2) an irreversible relaxation was observed. At irradiances of 10 W/cm2 and above initial relaxation was accompanied with constriction, focal coaguli, and hemostasis. Irradiation with the argon-pumped dye laser at 595 nm did not produce any significant relaxation. PMID- 2263152 TI - Effect of blood upon the selective ablation of atherosclerotic plaque with a pulsed dye laser. AB - Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques. PMID- 2263153 TI - Nd:YAG-laser in the microsurgery of frontobasal meningiomas. AB - Forty-three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor. The 1.32 microns Nd:YAG-laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments. Tumor shrinkage was achieved by radiating the tumor surface with the Nd:YAG-laser. This technique facilitated the microsurgical dissection and reduced the blood loss by half. The Nd:YAG-laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20% to zero. The postoperative quality of life was excellent with a complete rehabilitation in 76% of the patients. The use of the 1.32 microns Nd:YAG-laser improved significantly the results of microsurgery for frontobasal meningioma. PMID- 2263154 TI - Histologic comparison of the pulsed dye laser and copper vapor laser effects on pig skin. AB - Albino pig skin was exposed to the copper vapor (CVL) and flash-lamp pulsed dye (PDL) lasers at 578 nm with a 3 mm diameter spotsize over a range of fluences until purpura and whitening were first established. The total irradiation time was the parameter that was varied in order for the CVL to reach the desired fluence. The lowest fluence producing each clinical endpoint was designated the threshold fluence: 34 J/cm2 was required to produce purpura using the CVL compared to 7.5 J/cm2 with the PDL laser. Histologically, skin exposed to purpura fluences from the CVL revealed the presence of constricted, disrupted papillary dermal blood vessels with trapped RBC's within them which were unlike those exposed to PDL where the irradiated vessels were dilated and packed with masses of intravascular agglutinated RBC's. The whitening threshold fluences for the CVL and PDL lasers were 67 J/cm2 and 29 J/cm2, respectively. Streaming of epidermal cells and dermal collagen denaturation were observed in CVL irradiated skin, compared to occasional dyskeratotic epidermal cells and focal dermal collagen denaturation following PDL exposure. The mechanisms responsible for the clinical and histologic changes produced by the two laser systems are discussed. PMID- 2263155 TI - Comparison of the effect of multi-wavelength light produced by a cluster of semiconductor diodes and of each individual diode on mast cell number and degranulation in intact and injured skin. AB - Intact skin and partial thickness wounds in adult male Wistar rats were irradiated by pulsed, monochromatic light of different spectral wavelength peaks simultaneously and the effects on mast cell number and degranulation were assessed. The light was produced by a Biotherapy 3ML (Omega Universal Technologies) device utilizing a 21 semiconductor diode cluster probe emitting 6 different wavelengths in the red and near infrared part of the spectrum simultaneously, only one of the wavelengths (820 nm) being coherent. The duration of treatment was 4 minutes. The average power density, distributed over the surface area of the probe (19.62 cm2) was 45 mW/cm2. The average energy density at the wound site was 10.8 J/cm2. The effect of each of the wavelengths incorporated in the cluster probe was then examined separately. The average power density for each single probe was 120 mW/cm2, except for the 820 nm diode which was 400 mW/cm2. The average energy density was maintained at 10.8 J/cm2 as with the cluster probe. After 2 hours the rats were killed and the skin was removed, processed for light microscopy, and stained with toluidine blue to identify the mast cells. The numbers of the intact and degranulated mast cells were counted in 100 high power fields (i.e., over a total area of 20 mm2) in each irradiated specimen and compared to the sham-irradiated and untreated groups. To avoid bias, the slides examined were coded and evaluated blind. In intact skin, the cluster probe irradiation was followed by a statistically significant increase in the total number of mast cells compared to the sham-irradiated group, but the percentage of the degranulated mast cells was not affected. In the partial thickness wound, the cluster probe irradiation was also followed by a statistically significant increase in the total number of mast cells compared to the sham-irradiated group; however, there was, in addition, a significant increase in the percentage of degranulated mast cells. Concerning the single probes, only the 660, 820, 940, and 950 nm wavelength emitters produced statistically significant increases in both mast cell number and degranulation in partial thickness wounds. However, when intact skin was irradiated with probes emitting these wavelengths, although the total number of mast cells was increased significantly, there was no change in degranulation compared with the sham irradiated group. The effects observed were less than those of the cluster probe. No significant differences were found between the 870 and 880 nm wavelength irradiated, sham-irradiated, and untreated groups in either intact or injured skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2263156 TI - Trans-scleral application of a semiconductor diode laser. AB - We used a diode laser with an output power of 1 W through a fiberoptic light pipe (200 microns diameter) to deliver laser energy through the sclera of pigmented rabbits. Ciliary body destruction occurred with energy levels of 300-400 mW and exposure time of 0.5 sec. Retinal photocoagulation was achieved with energy levels of 200-500 mW in 0.5 sec. Histologic examination of acute lesions demonstrated thermal destruction of ciliary body processes and retina. Chorioretinal scar formation was observed clinically and histologically within 2 3 weeks. Our data indicate that the transscleral diode laser may be used for destruction of the ciliary body processes or peripheral retinal coagulation in pigmented eyes. PMID- 2263157 TI - Molecular surgery of the basement membrane by the argon laser. AB - Although the argon laser is used successfully to weld a number of different tissues, the underlying chemical and cellular mechanisms for this process are not precisely defined. Consequently, a biochemical model has been developed in vitro using the well-defined extracellular matrix from the murine Engelbreth-Holm-Swarm (EHS) sarcoma. Control and experimental samples of EHS basement membranes were irradiated with a Trimedyne argon laser at 500-3,000 Joules/cm2 at 0 degrees C. The samples were diluted into cold phosphate-buffered saline and allowed to gel at 35 degrees C. The time course of the gelation reaction was followed in a spectrophotometer at 360 nm. Irradiation reduced the absorbance 7.5-15% compared to controls and was independent of the dilution over a 10-fold range. Gelation was also measured by determining the amount of protein by the Bradford assay that could be collected by centrifugation at 10,000g for 10 minutes. Argon-irradiated samples had 30-40% less protein in the precipitate than the controls. The addition of 5 mM beta-mercaptoethanol to the EHS extract blocked the effect of the laser on the gelation reaction. In addition, when gelation was carried out in the absence of calcium and magnesium, there were no differences between laser treated samples and controls. The basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non-reducing conditions. No differences in the polypeptide composition were noted between irradiated and control samples using either Coomassie- or silver-staining techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263158 TI - CO2-welded venous anastomosis: enhancement of weld strength with heterologous fibrin glue. AB - The milliwatt CO2 laser was used to perform end-to-end anastomoses in canine jugular veins. There was a high disruption rate (50%) in laser-welded veins (n = 10). Fibrin glue (n = 17), formed from human fresh-frozen plasma, enhanced the weld strength decreasing the disruption rate (18%), resulting in an 82% patency which nearly equaled the contralateral sutured vein patency (93%). The bursting strength was improved with fibrin glue. Transmural necrosis was present initially in all groups but extended for a longer distance in the vessel wall in laser welded anastomoses. Sutured anastomoses exhibited a greater inflammatory response. In laser-welded anastomoses endothelial cells were not as confluent as in sutured anastomoses by six weeks. Carbon dioxide laser-welded end-to-end vein anastomoses appear to be impractical because they disrupt too easily. However, the addition of heterologous fibrin glue to the weld results in a reasonably strong anastomosis with histologic properties that may be beneficial in vein bypass grafts. PMID- 2263159 TI - Comparative bactericidal exposures for selected oral bacteria using carbon dioxide laser radiation. AB - Although relatively high CO2 laser energies have been shown to sterilize root canals, the response of several bacterial strains to decreasing exposures of CO2 laser energy remains unknown. Freshly grown bacterial cells were irradiated on glass microscope coverslips. A comparison of equivalent energy exposures with differing parameters was made on the bacterial viability. No statistically significant difference was found in the energy required to kill closely related bacterial species. However, the energy density required to kill greater than 99.5% of the bacteria is less than 200 J/cm2, much less than that shown to sterilize in a previous study. PMID- 2263160 TI - New instruments for laser surgery. AB - New instruments to facilitate laser operations are presented. These devices are based on the Kocher bronchocoele sound and are useful as dissecting tools and optical backstops to prevent iatrogenic injury. PMID- 2263161 TI - Effective depletion of glutathione in rat striatum and substantia nigra by L buthionine sulfoximine in combination with 2-cyclohexene-1-one. AB - The effects of L-buthionine sulfoximine (L-BSO), 2-cyclohexene-1-one and diethylmaleate (DEM) on the concentration of rat brain glutathione (GSH) were investigated. Both DEM and 2-cyclohexene-1-one, administered subcutaneously, produced marked and rapid reduction of brain GSH, but 2-cyclohexene-1-one appeared less toxic than DEM. Six hours after 2-cyclohexene-1-one (100 microliters/kg) the striatal GSH concentration was 35% of control values, whereas the level was 55% of controls at 24 h and 80% of controls at 48 h. Similar results were obtained with DEM (800 microliters/kg). L-BSO (3.2 mg), administered intracerebroventricularly, produced a slower depletion of brain GSH. A 55% reduction of striatal GSH was obtained 24 h after the administration, and the level was approximately 50% of control at 48 h. Thus, the effect of 2-cyclohexene 1-one and DEM is rapid in onset but relatively short lasting, whereas the disappearance of brain GSH after L-BSO is slower but the effect is more long lasting. By combining L-BSO with either 2-cyclohexene-1-one or DEM both a rapid and long-lasting GSH depletion was obtained that was more profound than after any of the drugs alone. The combination of L-BSO and 2-cyclohexene-1-one was well tolerated, but the combination of L-BSO and DEM led to death in half of the rats the second day after injection. The disappearance rate of GSH after L-BSO alone gives an estimate of the turn-over of GSH. We found the turn-over of GSH to be higher in the substantia nigra pars compacta than in the striatum. The present work suggest that L-BSO and 2-cyclohexene-1-one would be very useful for evaluation of the biological role of GSH in the central nervous system. PMID- 2263162 TI - Endogenous angiotensin II regulates hepatic angiotensinogen production. AB - We have investigated the effects of endogenous angiotensin II (ANG II) on hepatic angiotensinogen mRNA levels in rats. Changes in endogenous ANG II were induced by various sodium intakes (standard-, low-, and high-sodium) or by enalapril treatment. In a low sodium state for 2 weeks, angiotensinogen mRNA levels and plasma ANG II concentration increased 1.3-fold and 1.6-fold compared to those in standard sodium state, respectively. In a high sodium state, angiotensinogen mRNA levels and plasma ANG II concentration decreased by 42% and 56% compared to the standard sodierm state, respectively. Four hours after treatment with enalapril (3 mg/kg), angiotensinogen mRNA level and plasma ANG II concentration decreased by 25% and 12% compared to the standard sodium state, respectively. There was a close correlation between angiotensinogen mRNA level and plasma ANG II concentration (r = 0.79, P less than 0.01). These results suggest that endogenous ANG II may play an important role in the regulation of hepatic angiotensinogen synthesis. PMID- 2263163 TI - Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells. AB - We studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [14C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol (r = 0.65 p less than 0.0003). These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans. PMID- 2263164 TI - Transition from cytosolic to mitochondrial thymidine kinase during development in human fetal tissues. AB - The transition from cytosolic ("fetal") to mitochondrial ("adult") thymidine kinase, as detected by electrophoresis, was examined in six human fetal tissues of gestational ages 11-40 weeks. In all tissues there was an early period during development in which only the fetal form was detected, followed by a transitional period in which both fetal and adults forms were present, followed by a later period in which only the adult enzyme occurred. Transitional periods were 23-25 wk. gestational age for colon, 13-15 wk. for kidney, 18-20 wk. for liver, 14-18 wk. for lung, 34-36 wk. for serum, and 25-28 wk. for thyroid. In all cases, only the adult form was present by the time of birth and persisted during the first 18 months of extrauterine life. The adult form, but not the fetal form, was inhibited by dCTP. PMID- 2263165 TI - Substrate specificities and functions of the P450 cytochromes. AB - Currently, the major recognized biochemical functions of members of the large superfamily of P450 hemoproteins (referred to commonly as the cytochromes P450) include catalyses of the monooxygenations of a wide variety of endogenous and exogenous lipophilic chemicals. Substrates that have attracted the greatest attention thus far are steroids, fatty acids, eicosanoids, retinoids, other endogenous lipids, therapeutic agents, pesticides/herbicides, chemical carcinogens, industrial chemicals and other environmental contaminants and toxic xenobiotic organics of low molecular weight. Commonly, monooxygenation of such substrates results in the generation of metabolites capable of producing biological effects that are profoundly different (qualitatively as well as quantitatively) from those elicitable by the parent chemical per se. P45OXIX dependent conversion of testosterone to estradiol-17 beta provides a dramatic example. Thus, these hemoproteins serve as extremely important but, as yet, largely unpredictable regulators of the biological effects producible by endobiotics as well as by xenobiotics. Current focus is on the identification and acquisition of sequence information on hereto unidentified and/or uncharacterized P450 isoforms and ascertainment of the specific functions of specific, individual isoforms. The regulation of quantities and activities of such isoforms in specific species/tissues, understandably, is also of great current interest. This interest has been further intensified by recent results indicating that substrate specificity associated with one P450 may not be the same as the corresponding isoform derived from a different animal species. Recent technological advances promise to greatly hasten the acquisition of knowledge concerning the functions of these important hemoproteins. PMID- 2263166 TI - Effect of L-carnitine and acetyl-L-carnitine on the human erythrocyte membrane stability and deformability. AB - In this study we examined the effect of carnitine and acetylcarnitine on the human erythrocyte membrane stability and membrane deformability. Since erythrocyte membranes are impermeable to these compounds, we resealed erythrocyte ghosts in the presence of different concentrations of carnitine or acetylcarnitine. Resealed ghosts can be adequately studied in their cellular deformability and membrane stability properties by means of ektacytometry. Both carnitine and acetylcarnitine alter the membrane stability but not membrane deformability of the red cell membrane. Resealed ghosts containing 20, 50, 150, and 300 microM carnitine had 1.1, 1.6, 0.9, and 0.7 times the normal stability. While resealed ghosts containing 20, 50, 150, and 300 microM acetylcarnitine had 1.1, 1.5, 1.3, and 1.2 times the normal stability. Such changes were found to be reversible. We also conducted SDS PAGE of cytoskeletal membrane proteins from membrane fragments and residual membranes produced during membrane stability analysis, and unsheared resealed membranes in those samples where we observed an increase or a decrease of membrane stability. No changes in the cytoskeletal membrane proteins were noticed, even when the samples, prior SDS PAGE analysis, were treated with or without dithiothreitol. In addition, fluorescence steady state anisotropy of DPH in the erythrocyte membrane treated with carnitine or acetylcarnitine shows no modification of the lipid order parameter. Our results would suggest that both carnitine and its acetyl-ester, at physiological concentrations, may increase membrane stability in mature erythrocytes, most likely via a specific interaction with one or more cytoskeletal proteins, and that this effect would manifest when the erythrocytes are subjected to high shear stress. PMID- 2263167 TI - Tauro beta-muricholate is as effective as tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the rat. AB - Cholestasis and enhanced biliary leakage of proteins such as lactate dehydrogenase (LDH) and albumin are known to be induced by infusions of relatively toxic bile salts such as taurocholate (TC) and taurochenodeoxycholate (TCDC). Tauroursodeoxycholate (TUDC) was previously shown to prevent these bile abnormalities when simultaneously infused (1-5). In the present study, we examined whether tauro beta-muricholate (T beta-MC) has a similar effect. The enhanced biliary excretion of LDH and albumin induced by the infusion of TCDC at a rate of 0.4 mumol/min/100 g was markedly prevented by the simultaneous infusion of T beta-MC or TUDC at a rate one-fourth that of TCDC. Increased LDH level in plasma and hemolysis caused by the infusion of TCDC were also reduced by either T beta-MC or TUDC. These results indicate that T beta-MC has a preventive effect on TCDC-induced hepatobiliary changes, which is as efficient as that of TUDC as shown previously, suggesting that the 7 beta-hydroxy group is important for this hepatoprotective effect. Furthermore, our results suggest that beta-muricholic acid may also have clinical value since current reports demonstrate a beneficial effect of ursodeoxycholic acid on a variety of cholestatic conditions, including primary biliary cirrhosis. PMID- 2263168 TI - Dopamine antagonism does not potentiate the effects of oxytocin and vasopressin on prolactin secretion. AB - The roles of oxytocin and vasopressin on prolactin secretion were studied. Adult female Sprague-Dawley rats ovariectomized for two weeks and treated with a long acting estrogen, polyestradiol phosphate for one week were used. Hormone administration and serial blood sampling were accomplished through indwelling intra-atrial catheters which were implanted two days before the experiment. Both oxytocin (20 micrograms/rat) and vasopressin (5 micrograms/rat) stimulated prolactin secretion within 10 min after injection and the effects were diminished by 30 min. In animals pretreated with a small dose of dopamine antagonist, sulpiride (1 microgram/rat), the effect of TRH on prolactin secretion was repeatedly shown to be potentiated. Same pretreatments with two different time intervals (30 and 60 min) between sulpiride and oxytocin/vasopressin administration, however, had no effect on oxytocin- or vasopressin-stimulated prolactin secretion. A vasopressin analog, 1-deamino-[D-Arg8]-vasopressin (dDAVP), with antidiuretic but no vasopressor activity was also used in the study. It was found that unlike vasopressin, dDAVP had no effect on prolactin secretion. In conclusion, both oxytocin and vasopressin can have a stimulatory effect on prolactin secretion when given in vivo. Unlike TRH, however, the action of oxytocin or vasopressin was not augmented by pretreatments of dopamine antagonist. The action of vasopressin on prolactin secretion may be a side effect of its vasopressor activity. PMID- 2263169 TI - Effects of lorglumide on gastrin- and peptone-stimulated gastric acid secretion in rats. AB - This study in rats demonstrates that gastric acid secretion stimulated by infusion of gastrin 17-I yielding plasma concentrations in the physiological range is almost abolished by the cholecystokinin-receptor antagonist lorglumide. Furthermore, lorglumide also inhibited intragastric peptone stimulated gastric acid secretion by 43%. When compared to peptone stimulation with a saline background infusion, lorglumide infusion inhibited peptone stimulated gastric acid secretion only significantly in the late (20 to 30 minutes) part of stimulation, while the initial part (0 to 10 and 10 to 20 minutes) was not significantly inhibited by lorglumide. Both peptone stimulation and gastrin infusion significantly augmented serum gastrin concentrations, which were not significantly influenced by lorglumide. The serum gastrin concentrations achieved during gastrin infusion were higher than during peptone stimulation, however the differences were not statistically significant. It is concluded that lorglumide abolishes gastrin stimulated gastric acid secretion in rats, but only partly (43%) inhibits peptone-meal stimulated gastric acid secretion. In contrast to the gastrin infusion experiments, where lorglumide abolishes acid secretion during the entire study period, the compound inhibits gastric acid secretion more effectively towards the end of peptone stimulation than in the beginning. PMID- 2263170 TI - President's address. PMID- 2263171 TI - Sudden death in idiopathic giant cell myocarditis. AB - A rare case of idiopathic giant-cell myocarditis fatally affecting a middle-aged woman is presented. The circumstances of the fulminant and unexpected death were witnessed and reported by a relative. The confusing aspects of the 'Fiedler's myocarditis', the relation with more common forms of viral myocarditis and finally the medico-legal importance in the context of the sudden and natural death are mentioned. PMID- 2263172 TI - Electric shock devices and their effects on the human body. AB - Stun guns, shock batons and cattle prods are electric shock devices which can be used as weapons against the human body. Stun guns cause temporary incapacitation of the body whereas the other devices do not. The electrical outputs of examples of each type of device were measured using a digital storage oscilloscope at the moment when the device was discharged across resistors chosen to simulate the resistance of the human body. The outputs from the stun guns and the non incapacitating devices have characteristic waveform shapes and magnitudes: significantly, the peak current from the stun guns is two orders of magnitude greater than from the other devices. To understand the possible hazardous effects of these outputs on the human body, the output parameters were related to the available information on the effects of electric currents on the human body and on the electro-immobilization of farm animals. PMID- 2263173 TI - A comparison of male admissions to a special hospital 1970-71 and 1987-88. AB - Characteristics of 109 male patients admitted over a two-year period to a Special Hospital are described and discussed. Comparison is made with the results from a previous study conducted in another Special Hospital (Broadmoor) some fifteen years ago. Admissions still originate mainly from the courts, the penal system, and the NHS. However, the pattern of admissions has changed, influenced in part by the advent of the Regional Secure Unit programme, and the 1983 revision of the Mental Health Act. Very few admissions were diagnosed as suffering from a primary affective disorder. Patients suffering from psychopathic disorder had committed few crimes of murder and manslaughter. Possible reasons for these and other findings are discussed. It is concluded that the Special Hospitals continue to play a distinct and essential role. PMID- 2263174 TI - Changes in the use of the Mental Health Act 1983 four years from its inception in Leeds Eastern Health Authority. AB - The origins of recent mental health legislation are briefly reviewed. Practices in the spirit rather than the letter of the 1983 Act are compared by studying one hundred periods of detention at its inception and another hundred four years later. There had been little change, and improvement only in rates of use of emergency powers and very short Section 2s. PMID- 2263175 TI - Use of guardianship under the 1983 Mental Health Act. AB - The powers of guardianship under the 1983 Mental Health Act confer on the guardian powers to require the patient to reside in a specified place, to require attendance for treatment and to require access to the patient for appropriate health and social services personnel. This paper presents a descriptive study and analysis of the use of guardianship over a 5-year period in four geographical areas. Cases were collected retrospectively from a variety of sources and scrutinized systematically. Three cases of guardianship for mental impairment were excluded from the analysis leaving 23 patients with mental illness. All but two of the patients were female. Older patients, mostly with dementia, accounted for three-quarters of the sample and the majority of orders in this group were to require residence in an old people's home (usually with an apparently good outcome), though three were intended to facilitate home care. In most of the younger patients a functional psychiatric illness was diagnosed and powers were used to maintain the patient at home. The absence of a specific 'power to convey' needs to be resolved for elderly patients needing residential care. The use of guardianship orders to maintain older patients in the community needs further exploration. PMID- 2263176 TI - A non-invasive technique for age at death determination. AB - Several methods for age at death determination of human skeletal remains have been developed. These methods have, especially in combination, proved to be useful in making individual identification of skeletal material in forensic cases. This study is based on the known correlation between actual age and structural changes in trabecular bone tissue. Using X-rays taken from live individuals, it provides a useful non-invasive ageing technique for the forensic examiner. An initial pilot study defined five phases of age-related changes in the trabecular tissue of the proximal end of the femur. A total of 60 X-rays, randomly selected, and covering an age span from 14 years to 94 years, were subsequently scored in blind trials. The results demonstrate a clear relationship between age and changes in the trabecular structures. Based on this relationship it is possible to obtain an age estimate by identification of one of the five phases. An exact age determination of a single individual was not possible, but could be approximated to within 20 years. In forensic cases, however, where the removal of soft tissue is not always possible, this method can contribute to the final age determination when used in conjunction with other well-known methods, and thereby strengthen the final age estimate. PMID- 2263177 TI - A puzzle of skeletal remains: how forensic science and medicine succeeded in unravelling a complex and controversial murder case. AB - A case is presented where skeletal remains recovered from a remote, wooded area in Karnataka State of South India, which posed difficulties in identification were eventually successfully tackled by systematic forensic methods. Though most of these constituted well-established conventional techniques, the case can yet be considered as a fairly complex one beguiling some of the Scientific Investigators involved. PMID- 2263178 TI - A proven case of false confession: psychological aspects of the coerced-compliant type. AB - This paper describes the case of a 17-year-old youth who falsely confessed to two murders during police interrogation while not legally represented. He again confessed during a second interview in the presence of a duty solicitor, and later made further misleading admissions to prison staff and another inmate while at the beginning of his remand. The confession elicited by the police appeared very detailed and apparently convincing. The confession subsequently by chance proved to be false. It appears to have resulted from persistent pressure and psychological manipulation of a man who was at the time distressed and susceptible to interrogative pressure. Following the withdrawal of the charges by the prosecution and the conviction of somebody else for the offense, a detailed psychological assessment indicated a clear improvement in the man's ability to assert himself and to cope with interrogative pressure. The youth was of average intelligence, suffered from no mental illness and his personality was not obviously abnormal. PMID- 2263179 TI - A fatality due to the use of cantharides from Mylabris phalerata as an abortifacient. AB - A fatal case of attempting to procure abortion by the ingestion of the crude extract of cantharides from over 200 dried Mylabris phalerata is presented. The quantification of catharidin in blood, urine and liver by gas chromatography using trichloroacetic acid in the extraction process and butobarbitone as the internal standard is described. Ante- and post-mortem blood levels were found to be 0.27 and 0.11 micrograms/ml respectively. To conclude, the lack of legislative control in Hong Kong over Chinese herbal medicines is highlighted. PMID- 2263180 TI - Is hyperkalaemia the cause of sudden death in young healthy athletes? PMID- 2263181 TI - Drawing on memory: exploring the expertise of a police artist. AB - The use by the police of artists to draw likenesses of suspects is on the increase, yet there are few studies of their professional prowess. In the current study, art students observed one of six target faces before either drawing a likeness of the person themselves or collaborating with an experienced police artist. The likenesses produced by the police artist were judged as consistently superior to those made by the students, despite the artist working indirectly from the witnesses' verbal directions. Instructions to judge the target face in terms of likely character and personality led to better drawings than instruction to examine physical features when students worked with the artist but not when they drew on their own. These findings are discussed in terms of police practice and face processing theory. PMID- 2263182 TI - Estimating stature from the length of the lumbar part of the spine in Japanese. AB - In order to estimate the stature from the length of the lumbar part of spine (LLPS), studies were made on Japanese males (n = 42) and females (n = 29) autopsied in our laboratory during 1984-1987. Somatometry was performed on the stature and LLPS in centimetres, the latter being measured from the upper edge of the first lumbar vertebral body, to the promonitorium, along the anterior surface of the spine. LLPS were 19.9 +/- 1.19 cm in males and 18.6 +/- 0.84 cm in females (mean +/- S.D.). The regression equations calculated were as follows: stature in males = LLPS x 3.23 + 101.7; stature in females = LLPS x 2.31 + 110.8. The standard errors of estimate were 6.16 cm in males and 4.05 cm in females. This method is useful for estimating the stature of severely burned or mutilated bodies which have no limbs. PMID- 2263183 TI - [Intra-keloid excision and deferred corticoid infiltration in the treatment of keloids. University Hospital Center of Treichville-Abidjan]. AB - On a series of 38 keloid surgery patients the authors noted a strong female predominance and the frequency of ear lobule keloid. After some rather unsuccessful excision-suture of the keloid they recommend the intra- keloid excision to be followed by a late corticoid infiltration but deferred until the 15th day. The results obtained were encouraging but some researches have to be made with regard to the etiology of this affection which might probably resolve the therapeutic problem. PMID- 2263184 TI - [Iron deficiency and pregnancy. A survey in a Mother and Child Care Center in Niamey (Niger)]. AB - A survey carried out in a mother and child care Center in Niamey (Niger) in 1989 has revealed the association of a ferruginous deficiency phase II and III in pregnant women examined in the 8th month of their pregnancy and not presenting any sign of microcytic hypochromic anemia. A preventive and a curative therapy was proposed to these pregnant women in order to correct this ferruginous deficiency without waiting for a hypochromic anemia be evident. PMID- 2263185 TI - [Arterial hypertension in Thio (New Caledonia)]. AB - The high blood pressure is one of the main cardiovascular risk factors in New Caledonia as it is every where. A study carried out in THIO from August 1985 to August 1988 displayed a frequency and a seriousness not frequent (17.8 p.c. of hypertensives in the population over 30 years of age by applying strict criteria), noticeably in the Melanesian ethnic group and mainly in the women. Such a result ought to instigate complementary epidemiological surveys, but also to urge on an active policy of screening, prevention and treatment. PMID- 2263186 TI - [Semilunar dislocations. A report of 8 cases. (Orthopedic service-University Hospital Center of Treichville-Abidjan)]. AB - The authors have underlined in a study made on 8 observations that the lunate dislocation is scar. All their patients were men under 40 years old. Industrial injury was the most dominant cause. Using WITVOET and ALLIEU's classification, they noticed a predominance of perilunar and posterior dislocations (7/8 cases). Perilunar anterior dislocations and isolated scaphoid carpal dislocation have not been encountered. The treatment which has been orthopaedic or surgical has given moderate results: Good results = 4; Average result = 1; Bad results = 2; Non seen to again = 1 The authors think that a precocious diagnosis and an orthopaedic treatment in the forms detected early and surgical treatment in ancient forms are the only guarantee of a good functional result avoiding dread diseases such as carpal instability, radiocarpal arthrosis. PMID- 2263188 TI - [Bacteriology and epidemiology of shigellas isolated at the Army Hospital in Djibouti]. AB - In a space of 26 months 108 shigellas were isolated from 104 patients with sporadic and benign diseases. 90% of the subjects were young French. Both S. Dysenteriae and S. Boydii make up 21% of the strains studied. 13% of the germs are multiresistance. Multiresistance can enhance development of serious sickness if a virulent strain comes in. PMID- 2263187 TI - [A study of malaria morbidity in a pediatric hospital service in Benin (West Africa) in 1988 and 1989]. AB - Authors report on a prospective study about malaria morbidity, carried out from April 1988 to March 1989. Malaria diagnosis was based on: 1. An unexplained fever, hours before, during or after entrance. 2. A parasitic density superior to 3,000 trophozoites per mm3 of blood. 3. Efficacy of parenteral malaria therapy. Among 480 hospitalized children, 20% suffered from a malaria attack; 44% of malaria attacks occurred within 6 and 23 months of age. Thus, malaria incidence seems considerable in this urban and lagoon environment. Malaria attacks were observed all year long but with unequal seasonal rates of incidence. As regards malaria morbidity studies, we propose that rates of incidence should be calculated according to several parasitic density thresholds so as to be able to compare various works. PMID- 2263189 TI - [Epidemiology and prophylaxis of viral hemorrhagic fevers]. AB - A review of virus hemorrhagic fevers has been carried out. The different etiological agents belong either to arboviruses, either to related genera. The authors recall the main epidemiological aspects, in particular the transmission ways and means. Prophylaxis is to be taught of which behaviour can be taken in regard to a questionable case as well as permanent measures of control on the field. Although an extreme carefulness is necessary, the experience of the recent past years indicate that classical measures of isolation are generally adequate to prevent any emergence of secondary cases. PMID- 2263190 TI - [Extra-abdominal desmoid fibroma and pulmonary metastases. (New Caledonia)]. AB - A 22 years old Melanesian patient had a tumor in the anterior and external side of the left leg. Three times, this tumor had a surgical treatment, by resection, then an amputation of the leg. Always, its histological aspect was agreeing with a desmoid fibroma. After an evolution of 23 months time, metastases appeared in the lungs. Most of the authors don't agree the existence of metastases in these tumors. Four observations were reported in the literature, including one in 1989. They emphasize the difficulties of the histological diagnosis of these tumors. The metastases seems to be an argument in the evolution, which incites to modify the initial diagnosis as a fibrosarcoma in spite of the lack of obvious histological malignancy. PMID- 2263191 TI - [Management of an isolated thyroid nodule or a heterogeneous nodular goiter, when thyroid scintigraphy is not available (Tahiti)]. AB - Thyroidal nodes (non-cystic) always put forward some difficult decision. As a matter of fact, it would not be reasonable to undergo each time a surgical operation, but it would be catastrophic to abstain wrongly. When scintigraphy and mainly cyto-puncture are feasible, so a coherent decision can be taken. When they are not possible and when only ultrasonography is available, we propose that a decision be taken according to a comprehensive approach although each argument being individually disputable. PMID- 2263192 TI - Evolution of isopenicillin N synthase genes may have involved horizontal gene transfer. AB - The isopenicillin N synthase genes from three fungal species, three Gram-positive species, and one Gram-negative bacterial species share an unusually high sequence similarity. A phylogenetic analysis was carried out to determine which type of evolutionary scenario best accounts for this similarity. The most plausible scenario is one in which a horizontal gene-transfer event, from the prokaryotes to the eukaryotes, occurred at a time close to the divergence between the Gram positive and the Gram-negative bacteria. PMID- 2263193 TI - Origin of rat beta-globin haplotypes containing three and five genes. AB - We have reported in rat three adult beta-gene haplotypes containing either five or three genes. Detailed sequence analysis reveals that the leftmost gene is the major gene and that at the opposite end downstream lies the minor gene. All of the genes lying between them are minor-major hybrids indicating their origin by unequal crossing-over. In two haplotypes beta-globin genes were found with an L1(1) element inserted directly into IVS2. The described results allow the formulation of a pathway of mutational events leading from the ancient two-beta gene rodent ancestor through a three-gene haplotype to five-gene haplotypes, one of which is postulated to have arisen in common laboratory strains since their capture in the wild. PMID- 2263194 TI - Correcting parsimonious trees for unseen nucleotide substitutions: the effect of dense branching as exemplified by ribonuclease. AB - In a study of mammalian ribonuclease evolutionary rates, we applied the Fitch Bruschi correction to reduce the bias caused by an unequal sampling of taxa in different lineages. The correction was clearly appropriate but only up to a point. The analysis showed that the sampling of taxa within the pecora was sufficiently intense that no correction for unseen, amino acid-changing, nucleotide substitutions was required. It was also found that the ribonuclease gene was duplicated at least twice at the origin of the pecoran branch of the artiodactyls. PMID- 2263195 TI - Hierarchical analysis of population genetic variation in mitochondrial and nuclear genes of Daphnia pulex. AB - The geographic structure of Daphnia pulex populations from the central United States is analyzed with respect to isozyme and mitochondrial DNA variation. The species complex consists of cyclic and obligate parthenogens. A hierarchical analysis of population structure in the cyclic parthenogens by using a fixation index approach indicates that this is one of the most extremely subdivided species yet studied. This genetic structure, much of which accrues within 100 km, is certainly due in part to the limited dispersal ability of Daphnia. However, previous work has shown that fluctuating selection can account for the spatial heterogeneity in isozyme frequencies in these populations. This may explain why the population subdivision for the mitochondrial genome increases approximately three times as rapidly with distance as does that for nuclear genes, which is slower than the neutral expectation. The obligate parthenogens are shown to be polyphyletic in origin, evolutionarily young, and, in some cases, geographically widespread. PMID- 2263196 TI - The primary structure of langur (Presbytis entellus) pancreatic ribonuclease: adaptive features in digestive enzymes in mammals. AB - The primary structure of pancreatic ribonuclease from langur (Presbytis entellus) has been determined. This sequence differs from that of human pancreatic ribonuclease at 14 (11%) of the amino acid positions. Eight of these 14 differences involve changes of charge, with the langur enzyme having five fewer positive charges than the human enzyme. The difference in charge between human and langur ribonuclease may be an adaptation to the different requirements for a nondigestive and a digestive role, respectively. A number of similarities in expression, gene duplications, and properties between mammalian ribonucleases and lysozymes have been observed, indicating similar adaptations in both enzyme systems. PMID- 2263197 TI - The similarity index and DNA fingerprinting. AB - DNA-fingerprint similarity is being used increasingly to make inferences about levels of genetic variation within and between natural populations. It is shown that the similarity index--the average fraction of shared restriction fragments- provides upwardly biased estimates of population homozygosity but nearly unbiased estimates of the average identity-in-state for random pairs of individuals. A method is suggested for partitioning the DNA-fingerprint dissimilarity into within- and between-population components. Some simple expressions are given for the sampling variances of these estimators. PMID- 2263198 TI - Accuracy of estimating genetic distance between species from short sequences of mitochondrial DNA. PMID- 2263199 TI - The inclusion of an assay for inherited congenital malformations in the assessment of mutagenicity. AB - A number of national guidelines and regulations on the mutagenicity of chemical substances mandate the assessment of inherited genetic effects. While inherited congenital malformations represent a major component of genetically-based adverse human health effects, tests for such effects are not used by regulatory agencies to evaluate inherited genetic effects. This paper is intended to highlight some of the salient characteristics of inherited congenital malformations which promote a rationale for their use in a regulatory context. PMID- 2263200 TI - Prediction of the carcinogenicity in rodents of chemicals currently being tested by the US National Toxicology Program: structure-activity correlations. AB - CASE, an artificial intelligence structure-activity relational system, was used to predict the carcinogenicity of a group of chemicals currently being tested in rodent bioassays by the US National Toxicology Program. The 'learning set' for the CASE predictions consisted of the results of previous 252 rodent carcinogenicity bioassays. PMID- 2263201 TI - A prospective toxicity evaluation (COMPACT) on 40 chemicals currently being tested by the National Toxicology Program. AB - The computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) procedure has been used to determine the molecular conformation and electronic structure of a series of 40 chemicals (out of a total of 44). The procedure can evaluate whether they interact with the active site of cytochrome P450 I or to the binding site of the Ah receptor, and hence to manifest carcinogenicity/toxicity. This is in response to the recent publication by Tennant et al. and their invitation to participate in a prospective identification of potential mutagenicity/carcinogenicity of these 44 chemicals. Correlation of COMPACT with potential genotoxicity was 25/40 (63%); COMPACT also predicted toxicity/carcinogenicity in 10 chemicals (25%) considered to be potentially non-genotoxic (naphthalene, promethazine, resorcinol, p-nitrophenol, tricresyl phosphate, bis(bromoethyl) propanediol, 3,4-dihydrocoumarin, theophylline, triamterene and chloramine), and predicted the absence of toxicity in four chemicals (10%) considered to be potentially genotoxic (methyl bromide, hydrazoic acid, 2,3-dibromo-1-propanol and 1,2,3-trichloropropane). PMID- 2263202 TI - Cooked-food mutagens: current knowledge of formation and biological significance. PMID- 2263203 TI - Analysis of nine known or suspected spindle poisons for mitotic chromosome malsegregation using Saccharomyces cerevisiae D61.M. AB - We tested nine (cadmium chloride, chloral hydrate, colchicine, diazepam, econazole nitrate, hydroquinone, pyrimethamine, thiabendazole, thimerosal) of the 10 known or suspected spindle poisons of the coordinated programme to study aneuploidy induction sponsored by the Commission of the European Communities using Saccharomyces cerevisiae D61.M (mitotic chromosomal malsegregation system). Mitotic malsegregation of chromosome VII was induced by chloral hydrate, thiabendazole and thimerosal. Diazepam, colchicine, cadmium chloride, econazole nitrate, hydroquinone and pyrimethamine revealed no induction of chromosomal malsegregation. PMID- 2263204 TI - Effects of Salmonella genotypes and testing protocols on H2O2-induced mutation. AB - Hydrogen peroxide (H2O2) was shown to be mutagenic in a number of strains of Salmonella typhimurium. Strain SB1106p (hisC3108, hisO1242, pKM101), a newly constructed strain carrying the histidine mutation at a UGA chain-terminating codon, was more responsive to H2O2 than TA104 or TA102, the two hisG428 strains originally developed for detecting oxidative mutagens. The largest proportional increase in revertants of strain TA104 was in the fraction of intragenic deletions. Three other strains (TA97, SB1111 and SB1106) gave unequivocal positive responses to H2O2 in both the liquid pre-incubation procedure and standard plate incorporation procedure. The response of TA100 varied among experiments, ranging from negative to a weak positive. Variations in the catalase content among the tester strains did not correlate with the relative responses obtained in the mutagenicity assays. PMID- 2263205 TI - Bioassay-directed fractionation of 1-nitropyrene metabolites: generation of mutagrams by coupling reverse-phase HPLC with microsuspension mutagenicity assays. AB - We have performed bioassay-directed fractionation of a model complex mixture (rabbit lung S9-generated metabolites of 14C-radiolabeled 1-nitropyrene) by assaying reverse-phase HPLC fractions using two microsuspension mutagenicity assays. A forward-mutation assay measuring mutation at the gpt locus (8 azaguanine resistance) in Salmonella typhimurium TM677 was performed in a total volume of 100 microliters, and a reverse-mutation assay measuring mutation at the hisD3052 allele in S. typhimurium TA98 was performed in a total volume of 200 microliters. HPLC fractions were collected every 30 s for 45 min, resulting in 90 fractions per run. The HPLC chromatogram (absorbance at 280 nm) and the 14C profile were compared to the mutagenicity profiles (mutagrams) and to the mutagenic potencies of pure metabolites studied separately. The results indicate that a fine dissection of the mutagenic fractions can be obtained by coupling HPLC to microsuspension mutagenicity assays. Differences observed between the mutagrams generated by the two bacterial strains were most likely due to metabolic (nitroreductase) differences between the two strains. This method should be generally applicable to the bioassay-directed chemical analysis of complex mixtures. PMID- 2263206 TI - DNA synthesis in radiation-induced micronuclei studied by bromodeoxyuridine (BrdUrd) labelling and anti-BrdUrd antibodies. AB - DNA synthesis in radiation-induced micronuclei of Chinese hamster cells was studied as a function of time after irradiation using pulse labelling of cells with bromodeoxyuridine (BrdUrd) and an immunofluorescence technique with anti BrdUrd antibodies. It was shown with this technique that DNA synthesis in micronuclei corresponds with DNA synthesis in nuclei during S phase in approximately 98% of the micronuclei. The presence of radiation-induced micronuclei that are too large to be produced by acentric fragments alone was therefore attributed at least in part to DNA synthesis in micronuclei. A partially synchronized progression of micronuclei from G1 phase into S phase could be observed allowing the measurement of the duration of G1 phase in cells containing micronuclei. The duration of G1 phase in these cells agreed with the duration of G1 phase in unirradiated cells. PMID- 2263207 TI - Methylmethane-sulphonate and X-ray-induced mutations in the Chinese hamster hprt gene: mRNA phenotyping using polymerase chain reactions. AB - Alterations in the hprt gene of Chinese hamster cells were determined in 71 spontaneous, methylmethane sulphonate (MMS)- and X-ray-induced mutants, using the Southern blot hybridization technique. Among 41 MMS-induced mutants, deletions eliminating the whole gene were observed in 17 cases (41%). Analysis of 20 X-ray induced mutants revealed the presence of similar deletions in nine of them (45%). No evidence of deletion was found in 10 spontaneous mutants. To investigate the possibility of small deletions, 18 MMS-induced mutants were studied with probes derived from exons 3 and 9 but no evidence of specific deletion of these two exons was found. The polymerase chain reaction (PCR) was used to phenotype hprt transcripts in 48 MMS, X-ray and spontaneous Chinese hamster mutants by amplifying the coding region of their cDNA. Among 22 MMS-induced mutants the message was present in 16 instances; 11 had normal levels while three had much lower levels of transcription. A further two mutants had mRNA of reduced size as revealed by the use of primers for PCR 3' to those routinely used. An analysis of 20 X-ray-induced mutants showed the presence of hprt mRNA in 11 of them with five having low levels of transcription. Among six spontaneous mutants, four were negative for mRNA on standard Northern blots and in one the message was only detected after PCR amplification. Direct DNA sequencing of 10 mutants revealed the presence of base substitutions in five of them while a 7 bp deletion was found in another. No mutations were found in another four mutants, suggesting the presence of mutation outside the coding region. PMID- 2263208 TI - DNA sequence analysis of in vivo hprt mutation in human T lymphocytes. AB - We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (hprt) mutations that arose in vivo in the T lymphocytes of a normal male subject. In previous studies approximately 16% (23/141) of the mutants from this individual analyzed by Southern blot displayed large structural alterations in hprt. Thirty-two mutants without these large hprt structural alterations produced sufficient hprt cDNA for polymerase chain reaction amplification and DNA sequence analysis. Base substitutions in hprt cDNA resulting in missense mutations and one mRNA splicing aberration (inclusion of intron sequences) were observed in 18/32 of these these mutants; substitutions occurred at both AT and GC base pairs. Small deletions (3/32), a tandem change and a single base insertion were also observed among the hprt cDNAs. Exon skipping and inclusion of hprt intron sequences in the hprt cDNA were observed in an additional 9/32 of the mutants. Analysis of T cell receptor (TCR) gene rearrangements revealed that six of eight mutants with an identical hprt T----A transversion displayed the same TCR rearrangement pattern, indicating that they were clonally related and arose from a single in vivo mutational event. PMID- 2263209 TI - Cell replication and unscheduled DNA synthesis (UDS) activity of low molecular weight chlorinated paraffins in the rat liver in vivo. AB - The rodent carcinogen C12-chlorinated paraffin (C12-CP) has been evaluated for unscheduled DNA synthesis (UDS) activity in the rat liver in vivo. Evidence of cell proliferation was also assessed by measuring cells undergoing semi conservative DNA activity (S phase). No evidence of UDS was observed at doses up to 2 g/kg at either 2 or 12 h after dosing. Concomitant positive UDS responses were observed for the liver genotoxins N-nitrosodimethylamine, 4-aminobiphenyl, methyl methanesulphonate, 2-acetylaminofluorene, benzidine and 6 dimethylaminophenylazobenzthiazole. A strong positive response was observed in the cell proliferation assay for the test agent and the positive control agents quinoline and 4-acetylaminofluorene. These observations are discussed within the context of the rodent carcinogenicity reported for the same sample of C12-CPs as studied by the US National Toxicology Program. PMID- 2263210 TI - Possible methodologies for the detection and study of DNA sequence changes following mutagen exposure: magnetic enrichment in mutant DNA. AB - The restriction site mutation method described by Parry et al. (1990) for isolating mutant sequences directly from DNA is discussed and an additional enrichment step proposed using magnetic beads. PMID- 2263211 TI - Evaluating the ability of CASE, an artificial intelligence structure-activity relational system, to predict structural alerts for genotoxicity. AB - CASE, a structure-activity relational system, correctly predicts the presence of structural alerts in 36 of 39 molecules (sensitivity, 1.00; specificity, 0.83; concordance, 92%). The misclassification of two of the molecules is due to either ambiguous or previously unenunciated rules for defining structural alerts. PMID- 2263212 TI - Frameshift mutagenesis by acridines and other reversibly-binding DNA ligands. PMID- 2263213 TI - Adaptive response in human lymphocytes conditioned with hydrogen peroxide before irradiation with X-rays. AB - Cultured human lymphocytes were first exposed to a low 'conditioning' dose of hydrogen peroxide and, subsequently, irradiated with a 'challenge' dose of 1.5 Gy of X-rays in order to analyse the induction of an adaptive response to oxidative damage. A significant reduction in X-ray-induced chromosome damage was evident when H2O2 was given as a single 30 min pulse 24 h after setting up the cultures and the lymphocytes were exposed to X-rays at 48 h. In contrast, when the cells underwent a repeated exposure to H2O2 before irradiation the yield of aberrations was that expected from the combined treatment. PMID- 2263214 TI - Relationship between carcinogenicity in rodents and the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells. AB - Two independent analyses were carried out to compare the induction of sister chromatid exchanges and of chromosomal aberrations as predictors of carcinogenicity. Using both a classical and a Bayesian approach, as well as by analysis of the structural fragments generated by CASE, an artificial intelligence system, it is included that individually neither of these tests is a satisfactory predictor of carcinogenicity. However, because the analysis revealed that each of the cytogenetic assays responds to a different set of structural features associated with carcinogenicity, it can be concluded that the assays can be included in a battery of tests to improve predictivity. PMID- 2263215 TI - Genotoxic activity of nickel subsulphide alpha-Ni3S2. AB - Four mutagenicity tests of alpha-Ni3S2 were performed: the Ames test on five Salmonella typhimurium strains, HPRT test on V79 cells, in vitro chromosomal aberrations on human lymphocytes and the in vivo micronucleus test in mice. The in vitro tests were carried out without metabolic activation. (i) The Ames test (5-1500 micrograms/plate) demonstrated no mutagenic activity, thus confirming previous observations by other authors. (ii) The HPRT test was carried out under standard conditions (3 h exposure) with alpha-Ni3S2 concentrations from 30 to 1000 micrograms/ml. No significant difference was observed with the control cells. Ultrastructural examination revealed alpha-Ni3S2 binding to the cell membrane. Very few particles were found in the cytoplasm but not in the nucleus. (iii) In vitro metaphase analysis in human lymphocytes were performed after exposure to total alpha-Ni3S2 suspension and to the soluble fraction in culture medium with or without fetal calf serum (FCS) (3-100 micrograms/ml, 24 h exposure). Nickel concentrations in the soluble fraction were determined by electrothermal atomic absorption spectrometry. A clastogenic effect of alpha Ni3S2 became evident under all experimental conditions with a significant additional increase of chromosomal aberrations in 20% FCS complemented medium. No difference was observed between total suspension and soluble fraction. (iv) The micronucleus test confirmed the clastogenic effect of alpha-Ni3S2 in vivo after administration of 250 mg/kg (i.p.). This test revealed a clear increase of micronuclei frequency in polychromatic erythrocytes 24, 48 and 72 h after the treatment. In addition, we observed a statistically significant decrease in the number (%) of polychromatic erythrocytes after 24 and 48 h exposure. The soluble, i.e. cell-entering, fraction seems to play a great part in the clastogenic effect, as has also been shown with other test methods by other authors. PMID- 2263216 TI - Aneuploidy induced by chloral hydrate detected in human lymphocytes with the Y97 probe. AB - Chloral hydrate (CH) has been assayed for its ability to induce chromosome number variation in human lymphocytes in culture. Aneuploidy induction has been detected by means of in situ hybridization on interphase nuclei with a chromosome Y specific DNA probe. A dose-dependent increase in the number of hyperdiploid nuclei was found at CH concentrations ranging from 250 to 750 micrograms/ml. These results represent a further contribution to the validation of the method which gave a positive response with drugs characterized by different mechanisms of action and therefore may be of general use in detecting aneuploidy in mammalian cells. PMID- 2263217 TI - Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. III: Measurement of mutant frequency to 6-thioguanine resistance. AB - The mutant frequencies (MF) at the HPRT locus of peripheral blood lymphocytes collected from breast cancer patients before and after treatment according to a defined protocol of the Institut Curie were compared to those from healthy donors. The treatment involved either a local radiotherapy (RT1) followed by a chemotherapy (CT2) or a chemotherapy (CT1) followed by a radiotherapy (RT2). In accord with others, we observed no significant difference in the MF to 6 thioguanine resistance (6TG) in T lymphocytes in the control and breast cancer groups before treatment. When the effect of CT or RT either alone or in combination was analysed, the increase observed in MF can be wholly accounted for by the effect of radiation. In this study, the effect of chemotherapy on mutation did not achieve significance. Circulating T lymphocytes are mainly in the G0 phase of the cell cycle and thus would not be mutated by drugs which preferentially affect dividing cells, whereas such cells could still mutate when submitted to ionizing radiation. PMID- 2263218 TI - Clastogenicity of PvuII and EcoRI in electroporated CHO cells assayed by metaphase chromosomal aberrations and by micronuclei using the cytokinesis-block technique. AB - The clastogenicity of two restriction endonucleases with almost equal cutting frequencies: PvuII, generating blunt-ended DNA double-strand breaks (dsb) and EcoRI, generating cohesive-ended dsb, has been measured after treatment of electroporated CHO cells with these enzymes. Chromosome damage was assessed by the micronucleus cytokinesis-block technique, and for certain electroporation voltages by analysis of metaphase preparations. As has been found in previous studies, PvuII was found to be more effective in causing chromosomal damage than EcoRI, indicating the greater importance of blunt-ended dsb in chromosome aberration induction. These findings also validate the use of the micronucleus cytokinesis-block technique for evaluating chromosomal damage from restriction endonucleases. The results show a biphasic induction of micronuclei in binucleate cells as a function of time after treatment. This pattern is interpreted as indicating variable sensitivity of cells to restriction endonucleases at different stages of the cell cycle. The micronucleus data show that late collection times (40-48 h after treatment) give higher frequencies than short times. Both micronucleus and metaphase aberration data indicate that voltages in excess of 260 V are more efficient in porating cells than lower voltages and, as a result, lower restriction endonuclease concentrations could be used. PMID- 2263219 TI - Comparison of chromosome aberration frequency and small-colony TK-deficient mutant frequency in L5178Y/TK(+/-)-3.7.2C mouse lymphoma cells. AB - The L5178Y/TK(+/-)-3.7.2C mouse lymphoma assay is used to quantitate the induction of thymidine kinase (TK)-deficient mutants. The mutants detected in the assay form colonies that can be distinguished as large or small. The induction of small-colony mutants has been associated with the induction of chromosome mutations. In the present paper, we compare the analysis of induced small-colony TK mutants with gross aberration analysis (the more classical approach to analyzing chromosomal damage). Data are presented for 34 mutagens. As expected, we find that while the induction of gross aberrations and the induction of small colony TK mutants is correlated, there is no simple mathematical relationship between the two endpoints. The two markers evaluate different subpopulations of chromosome mutations. While either endpoint can be used to detect chromosomal mutations, it should be remembered that the small-colony TK mutants represent genetic events which are compatible with cell viability. Only those alterations compatible with cell viability are a significant risk for human carcinogenicity or mutagenicity. PMID- 2263220 TI - Industrial Genetic Toxicology Discussion Group. Spring meeting 1990: "Molecular aspects of genotoxicity". PMID- 2263221 TI - Hormone replacement therapy: use patterns in 51-year-old Danish women. AB - A survey based on a postal questionnaire sent to all women born in 1936 living in four Copenhagen suburbs (n = 597, response rate = 88%) revealed an overall prevalence of hormone replacement therapy (HRT) use of 22% and a cumulative incidence of 37%. This paper describes the use of HRT in this population and the patterns of exposure to treatment. Our results indicate that the use of HRT, particularly combined oestrogen-progestogen therapy, is increasing and is being initiated during the pre-menopause. Climacteric complaints were the main reason for starting treatment; only a minority of the respondents were motivated by prophylactic considerations. Forty percent discontinued treatment, the majority stating that they had done so because of unpleasant adverse reactions or lack of effect. PMID- 2263222 TI - [Growth and spore germination factors of various strains of Bacillus sphaericus]. AB - The work was aimed at studying the requirements of sixteen Bacillus sphaericus strains with a different larvicidal activity in amino acids and some other compounds necessary for their growth and spore germination. Most of the strains were found to require arginine, glutamate, methionine, threonine, serine, glycine, alanine and lysine, but they did not assimilate phenylalanine and proline. Arginine, methionine and glutamate were shown to be the most effective inductors of spore germination. Specific differences were detected in the requirements of virulent and avirulent strains. Glucose repressed both spore germination and spore formation. PMID- 2263223 TI - [Characteristics of microbial association in secretions of various mammalian sebaceous glands]. AB - The following secretions of mammalian skin glands were subjected to a microbiological survey: the middle-abdominal glands of great and Mongolian gerbils, the preputial gland of musk deer, the perineal organ of African civet cat, the interdigital skin regions and interdigital glands of bison, European bison, European roe deer, and musk deer. All the secretions were found to contain microbial associations. The composition of bacterial species in the secretions and the quantity of microorganisms varied among different animal species, during the ontogenesis of an animal, and depended on the topography of a gland on an animal body as well as on its functional state in different seasons or upon hormonal changes. The secretions of certain glands contain factors which determine the composition of microbial species in a particular ecological niche and the stability of such a cenosis. PMID- 2263224 TI - [Plasmids controlling biodegradation of epsilon-caprolactam]. AB - Bacterial strains (190) capable of growth on epsilon-caprolactam as a sole source of carbon and nitrogen were isolated from epsilon-caprolactam industrial sewage. Most of the strains (90%) were found to contain plasmids. Some of the strains (36.8%) assigned provisionally to the genus Pseudomonas contained plasmids controlling epsilon-caprolactam catabolism. The plasmids had a molecular mass from 50 to 300 MDa. Certain plasmids differed in the frequency of conjugation transfer and in the presence of other genetic determinants (resistance against heavy metal ions) and also determined the different character of bacterial growth on epsilon-caprolactam and on its intermediate catabolites. PMID- 2263225 TI - [Physico-chemical properties of DNA from representatives of a population of Pseudomonas bacteriophages]. AB - Twenty-four bacteriophages of Pseudomonas similar in terms of their morphology and structure were studied. The genomes of 23 bacteriophages from a population widespread in Belorussia and of one bacteriophage from the Krasnodar Region were shown to be double-helical DNAs with the content of GC base pairs from 46.8 to 66.7%. Four endonucleases (Eco R1, Hind III, Bam H1, and Eco RV) were used in the restriction analysis. Phage 8 which differed from the other phages in the area of its distribution was found to represent an individual group. The other phages were subdivided into eight related groups and had an identical restriction map within each group. The mean molecular masses of phage DNAs calculated by the method of summing the molecular masses of restricts ranged from 27.8 to 31.0 MDa. PMID- 2263226 TI - Phosphorylcholine antibodies in pulmonary infection. AB - Phosphorylcholine (PC) antibodies in serum from patients with pulmonary infection, and from normal individuals, were studied. Anti-PC antibodies were detectable in the serum from normal individuals at mean concentrations of 320 micrograms/ml for the IgG class and 110 micrograms/ml for the IgM class. Concentrations of anti-PC antibodies which were higher than normal for both the IgG and IgM classes were observed in the serum in pulmonary infection (1,440 micrograms/ml and 210 micrograms/ml, respectively). Despite the significant difference in the concentration of anti-PC antibodies, the PC-specific B cell precursor frequency in the peripheral blood lymphocytes showed no difference between normal individuals and the patients with pulmonary infection, or between the acute phase and the chronic phase in a single patient with chronic pulmonary infection. Serologically, the purified IgG anti-PC antibody did not share the cross-reactive idiotype of TEPC 15, which is the most common idiotype of the murine anti-PC antibodies. However, the purified IgM anti-PC antibody expressed a very weak cross-reactive idiotype of TEPC 15. It appears from these studies that human anti-PC antibodies may play an important biological role in pulmonary infection by microorganisms which possess a PC determinant. PMID- 2263228 TI - Health care in the United States: who is minding the indigent? PMID- 2263227 TI - Proliferative response of synovial fluid and peripheral blood mononuclear cells to arthritogenic and non-arthritogenic microbial antigens and to the 65-kDa mycobacterial heat-shock protein. AB - Cellular immune responses to microbial antigens have been implicated in the pathogenesis of some forms of arthritis including reactive arthritis, Reiter's syndrome, ankylosing spondylitis and rheumatoid arthritis. We investigated the proliferative T cell responses of paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MC) to so-called arthritogenic bacteria (Yersinia enterocolitica and Salmonella typhimurium), to control antigens, such as Candida albicans, mumps virus and purified protein derivative, to the recombinant mycobacterial 65-kDa heat-shock protein (hsp 65) and the mitogen phytohemagglutinin (PHA) in 16 patients with different inflammatory rheumatic diseases. The [3H]thymidine uptake of unstimulated cells (medium control) as well as the proliferative response to the different antigens tested was markedly increased in SFMC irrespective of the underlying rheumatic disease. In contrast, mitogenic stimulation was decreased in SFMC. The proliferative response to the hsp 65 correlated significantly with the responses to Yersinia, Salmonella and Candida. These results may reflect an enhanced function of SF antigen-presenting cells, different functional properties and subset distributions of PB and SF T cells with a preferential accumulation of helper-inducer/memory T cells or a maintenance of an ongoing immune response by T cells cross-recognizing self epitopes such as epitopes located on the hsp 65. Thus, care should be taken in the interpretation of SF T cell responses to microbial antigens as diagnostic tools in arthritis. PMID- 2263229 TI - Investiture. PMID- 2263230 TI - So much for the living will. PMID- 2263231 TI - Tuberculosis. PMID- 2263232 TI - The prevalence of nonpharmacologic measures of blood pressure control in Missouri. PMID- 2263233 TI - Pancreatitis coexisting with a large cystadenoma of the pancreas. PMID- 2263234 TI - Superior sulcus tumors. AB - Superior sulcus tumors are rare primary pulmonary tumors of the thoracic inlet that have a distinct presentation. In this article, the authors stress currently accepted measures in the diagnosis, surgery and postoperative treatment of superior sulcus tumors. PMID- 2263235 TI - Paraneoplastic syndromes of the nervous system: manifestations of the occult and the obvious. AB - Cancer patients are plagued by a wide variety of medical problems, among them paraneoplastic syndromes of the nervous system. The authors present a review of some of the syndromes these patients endure. PMID- 2263236 TI - [The effects of the responses to surgical stresses]. PMID- 2263237 TI - [Induction of lymphokine activated killer (LAK) and prolongation of its activity by intrasplenic injection of interleukin 2 (IL-2) in combination with tumor necrosis factor (TNF)]. AB - We have so far investigated the method to induce LAK cells efficiently within the body by direct intrasplenic injection of Interleukin 2 (IL-2) in tumor bearing mice. In this study we used IL-2 in combination with rTNF in an attempt to induce effectively much stronger LAK cells and found that the combined use resulted in not only enhancement but also significant prolongation of LAK activity. Furthermore, the combined use also yielded in vivo effect, that is prolongation of the mouse survival. This study suggests that the combined use of IL-2 and TNF may promise more effective induction of LAK cells in the organism with much smaller doses of IL-2. The combined use may be helpful to improve the treatment regimen by intra arterial injection of IL-2 that we have so far conducted, possibly leading to a higher response rate in clinical setting. PMID- 2263238 TI - [Analysis of methicillin-cephem resistant Staphylococcus aureus (MRSA) hospital infection and toxigenicity of MRSA]. AB - MRSA infectious diseases were often observed in our ward including general, pediatric and neurosurgery during recent two years. Following items were investigated for analysing a prevalence of the infections; 1) the frequency of MRSA in Staphylococcus aureus isolates from clinical materials, 2) the monthly number of patients with MRSA infectious diseases, 3) the biologic types and the toxigenicity of MRSA isolates from clinical materials, nasal carriers and an environmental material in the ward. The results were as follows. 1) Methicillin cephem resistant strain was determined in 204 of 247 Staphylococcus aureus isolates (83%). 2) Monthly registration showed a trend that an increased number of the patient in one unit was followed by an increase in other units. 3) Most of MRSA isolates were classified into type II coagulase and two kinds of strains were predominantly found in isolates from clinical materials by plasmid DNA analysis. Most of MRSA isolates had capabilities of producing type C enterotoxin and toxic shock syndrome toxin-1 (TSST-1). The results suggested that the frequent MRSA infectious diseases attributed to hospital infection. Since hospital infection of virulent MRSA may cause serious infectious diseases, much concern to inhibit the spread of this organism should be required. PMID- 2263239 TI - [A clinical study of immunological status in gastric cancer patients--with special reference to T-cell subsets in the lymphocytes of regional lymph nodes]. AB - Non-metastatic regional lymph node lymphocytes of 41 patients with gastric cancer were studied by using different monoclonal antibodies and flow cytometry. Used monoclonal antibodies were OKT3 (total T; CD3), OKT4 (helper/inducer T; CD4), OKT8 (suppressor/cytotoxic T; CD8) and Leu11 (NK/K cell; CD16). The results were as follows: 1. The percentage of CD3 cells and CD4 cells were about ten point fewer in lymph nodes than in peripheral blood. 2. CD8 cells were found to be one half or one third lesser in lymph nodes than in peripheral blood. 3. CD16 cells were found to be rare in lymph nodes. 4. The percentage of CD3, CD4 and CD8 cells were higher in distal lymph nodes than proximal ones. 5. The percentage of CD3, CD4 and CD8 cells were not different with progression of the cancer, whereas CD3 cells and CD8 cells were decreased in lymph nodes of stage IV. 6. The percentage of CD8 cells was higher in distal nodes of stage III. Regional lymph nodes are necessary to protect against cancer metastasis, and killer T cells and cytotoxic T cells were fewer in lymph nodes. These results suggested that killer activity and cytotoxicity of the lymph node lymphocytes are inactive and anergy. PMID- 2263240 TI - [Experimental and clinical study for spread of cardiac cancer to the diaphragm]. AB - We investigated the route of lymphogenous metastasis of cardiac cancer to the diaphragm, making a model of cardiac cancer using VX2 tumor of rabbit. Metastasis ratio of each lymph node in the experimental model indicated a correlation with clinical cases. Histological investigation of the diaphragm indicated floating of VX2 cancer cells in the lymph vessels in the diaphragm in 4 of 20 cases (20%). After, injection of CH44 at the oral side of the tumor, the presence of CH44 in the lymph vessels in the diaphragm were seen in 6 of 16 cases (37.5%). Clinically, the left diaphragm was excised as wide as possible in 22 cases of cardiac cancer with esophageal invasion by left thoraco abdominal approach. Histologically, embolic of the tumor or floating tumor cells in the lymph vessels in the diaphragm were seen in 6 of 22 cases (27.3%). These results revealed that carcinoma proliferating in the cardia can apparently spread to the diaphragm more extensively than has been previous believed. PMID- 2263241 TI - [Bone disorder after gastrectomy--clinical & experimental studies]. AB - To study the pathophysiology of bone disorder after gastrectomy, 320 patients and 40 Wistar male rats were used. Clinically, patients who had received gastrectomy 1-15 years previously, were examined for skeletal symptoms, serum biochemistry, microdensitometry of second metacarpal bone, and 20 of them were then studied in a calcium infusion test. Using microdensitometry, abnormality of bone metabolism was observed in 38% of the patients. In severe cases, a significant decrease of serum Ca. and increase of alkaline phosphatase were observed (p less than 0.05), 65% complained of joint pain. In the calcium infusion test, severe cases showed a low urinary excretion of Ca, like osteomalacia, and unlike osteoporosis. Experimentally, body weight & amount of food intake decreased and fatty diarrhea was observed in rats after total gastrectomy. Skeletal changes including thinning of the cortex, loss of medullary trabeculation & decrease of bone ash and biochemical changes such as low serum Ca. 25(OH)D3, 24, 25(OH)2D3 and high iPTH levels were observed. Also the bone formation rate was lower than control as detected by tetracycline double labelling method. As low food intake & fatty diarrhea after gastrectomy which result in Ca. & vit. D insufficiency may be the major etiology of bone disorder. PMID- 2263242 TI - [Flow cytometric analysis in colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis]. AB - Nuclear DNA ploidy studies were performed by flow cytometry on extracted nuclei from 65 heptic metastases from colorectal cancer. In 25 patients, both primary and metastatic lesions were available for analysis. Primary carcinomas were DNA diploid pattern in 48.1%, DNA aneuploid in 51.9%. Of 31 hepatic metastases, 11 (35.5%) metastases showed a DNA diploid pattern, and 25 (64.5%) showed a DNA aneuploid pattern. Ploidy pattern was constant between primary and metastases in 80% of tumors. No significant relationship between metastatic characteristics and DNA ploidy pattern was found. The DNA aneuploid cancers had a relatively poorer prognosis in patients with unresectable hepatic metastasis. In resected hepatic metastases from colorectal cancer, rate of hepatic recurrence with DNA diploid pattern was lower than that with DNA aneuploid pattern. Survival of patients with DNA diploid metastases (71% alive at 5 years) was significantly better than that of patients with DNA aneuploid metastases (21% alive at 5 years) (p less than 0.05). These results demonstrated that flow cytometric DNA ploidy measurements may have prognostic value for patients with hepatic metastases from colorectal cancer. PMID- 2263243 TI - [An experimental study on shock after temporary hepatic inflow occlusion and platelet activating factor (PAF)]. AB - The potential effect of CV6209, a platelet activating factor (PAF) antagonist, on shock after temporary hepatic inflow occlusion was investigated. Five groups of rats were given following chemicals i.v. (Group A: both 3 mg/kg of CV6209 and 100 U/kg of heparin, Group B: 3 mg/kg of CV6209, Group C: 100 U/kg of heparin, Group D: 4 ml/kg of normal saline, Group E: 4 ml/kg of normal saline under splanchnic decompression with port-jugular bypass) and were subjected to 45 minutes of hepatic inflow occlusion. The survival rates 24 hours after the occlusion were 80%, 60% 45%, 30% and 80% in groups A, B, C, D and E, respectively. All rats except for those in group E developed hypotension during the occlusion period. The blood pressure was reversed to pre-occlusion level after declamping in groups A and B, although hypotension continued in groups C and D. Blood chemistry also revealed diminished elevation of serum mitochondrial GOT after the occlusion in PAF antagonist group. These results suggest that portal congestion is the most responsible for shock and death after temporary hepatic inflow occlusion and PAF is a mediator of the injury. PMID- 2263244 TI - [Clinical results of selective treatment for flail chest]. AB - A better understanding in pathophysiology of flail chest has brought an evolution to the principles of it's management. The methods of stabilization changed from surgical to pneumatic measures and now, a concept of conservative treatment is recognized. Adhering to our protocol for flail chest, which essentially limits mechanical ventilation, we have prospectively treated 36 patients since 1981. The patient were divided into two groups according to their need for mechanical ventilation. There were 16 patients (44.4%) in a group treated in conservative manner and with no mechanical ventilation (Group A). There were 20 patients (55.6%) in a group treated by mechanical ventilation (Group B). Group A had 6.2% incidence of pneumonia, 3.6 days average stay in ICU and mortality rate of 0%. Group B had 75% pneumonia, 22.5 days average in ICU and 15% mortality. Group B patients required respiratory support for 14 days average, which was not reduced by surgical stabilization. Restrictive pulmonary disturbance in group A was milder than that of group B, and this again was not affected by surgical stabilization. We conclude that 40% of flail chest are controllable without mechanical ventilation and that the result of this conservative therapy is superior to any other treatments. PMID- 2263245 TI - [1989 clinical experience with biomedicus centrifugal pump in the operation of the thoracoabdominal and thoracic aneurysm--assessment from the point of renal function]. AB - It is generally accepted that operative procedures of thoracic aneurysm requires the use of some type of temporary vascular bypass when cross clamp is necessary. Past 10 years, we have used three types of temporary bypass. From 1979 to 1989, 78 patients with thoracic aneurysm were treated. In these patients, 25 patients with descending thoracic and thoracoabdominal aneurysm were divided into three groups on the basis of the type of bypass and evaluated from the point of postoperative renal function. Temporary vascular bypass using artificial graft was applied to 9 patients. Gott's shunt tube in stead of graft was used in 5 patients. Left ventricular bypass with Bio-Medics centrifugal pump was used in 11 patient. Among three groups, differences in age, diameter of the aneurysm, preoperative renal function and aortic clamp time were statistically not significant. Mean arterial pressure gradient between upper and lower extremities were 42 +/- 14 mm Hg in artificial graft group, 31 +/- 7 mm Hg in Gott group and 9 +/- 10 mm Hg in Bio-Pump group. Urine volumes during temporary bypass were 98 +/- 43 ml in artificial graft group, 120 +/- 54 ml in Gott group, 255 +/- 269 ml in Bio-Pump group. Left ventricular bypass with Bio-Medics centrifugal pump is an extremely useful method to protect renal function in thoracic aneurysm surgery. PMID- 2263246 TI - [Histologic characteristics of the pathologic processes in thromboangiitis obliterans (Buerger's disease)]. AB - In order to elucidate histologic characteristics of the pathologic processes in thromboangiitis obliterans (Buerger's disease) a histopathologic study of amputated legs of 9 patients diagnosed as this disease was carried out. The ages of the patients ranged from 27 to 47 years, all male, and the duration of symptoms prior to amputation was between 3 and 11 years. All of the patients had no history of hypertension. The initial stage of the pathologic processes was characterized by contraction of small arteries of legs followed by intimal thickening with laminar elastosis, the subsequent stage by occlusion of arterial lumens by both thrombosis and following organization and recanalization which occurred in the small arteries, and the later stage by lymphocytic infiltration of the arterial walls, suggesting some immunological mechanisms involved in the pathogenesis. Accompanying venules demonstrated similar processes to those of small arteries, which enhanced the local circulatory disturbances. PMID- 2263247 TI - [Experimental and clinical study on extracorporeal membrane oxygenation (ECMO) for newborn respiratory failure]. AB - Simple method of venoarterial (V-A) bypass was developed for neonatal ECMO. Technical aspects in the management of our device was shown in this report. The most important technique was to keep the flow of ECMO less than 60-80 ml/min/kg. The low flow circulation less than 80 ml/min/kg made puppies alive under apnea experimentally. Clinically we experienced four newborn cases. All cases had severe respiratory failure with AaDO2 above 580 mmHg due to congenital diaphragmatic hernia. Two cases of them were able to survive. Other two cases died from intracranial hemorrhage during ECMO. The oxygenation of all cases was satisfactory under relative low flows. Our simple ECMO circuit was not only easy to operate but also to give less damage to blood. PMID- 2263248 TI - [Postoperative pancreatitis following thoracoabdominal aortic aneurysmectomy--a case report]. AB - Thoracoabdominal aortic aneurysmectomy with a temporary bypass from left axillary to right common iliac artery was successfully performed in a 57 year-old-female with an aneurysm involving celiac, superior mesenteric and renal arteries. An elevation of serum amylase level with a peak value on 7 POD was observed and ultrasonography revealed acute pancreatitis resulting from seventy minutes ischemia of celiac artery during the procedure. The patient was treated conservatively and discharged. It seems to be important to prevent pancreatic ischemia in thoracoabdominal aortic aneurysmectomy as well as to maintain renal and hepatic circulation. PMID- 2263249 TI - [Venous aneurysm of V. saphena accessoria--a case report]. AB - A 43-year-old male was admitted for subcutaneous mass of rt. inguinal lesion. Saccular dilatation of vein is a rare phenomenon and usually termed "venous aneurysm". Venous aneurysm has been reported in the following vein: face, neck, extremities, superior vena cava region, portal vein region and by-pass grafting vein. This is the 1st report of a venous aneurysm found in V. saphena accessories in Japan. The true etiology is unknown, but underlying causes which produce damage to the venous wall (trauma, inflammation, congenital weakness, and localized degenerative change) have been mentioned as possible causes. Rarely, thrombosed venous aneurysm may cause pulmonary emboli. Definitive diagnosis is established by venography. Venous aneurysm often increases or reduces in size according to the change of venous pressure by proximal vein compression postural change and Valsalva maneuver. In general, surgical resection of the aneurysm is the treatment of choice. PMID- 2263250 TI - [Therapeutic effect of superoxide dismutase in combination with an antimicrobial agent on experimental peritonitis: preliminary report]. PMID- 2263251 TI - [Serum type IV collagen (7S domain) levels as the marker of hepatic metastases in gastrointestinal carcinomas: preliminary report]. PMID- 2263252 TI - [Influence of surgical stress on IL-1 and TNF production by blood monocyte in cancer patients: preliminary report]. PMID- 2263253 TI - [Effect of selective administration of monoclonal anti-T-cell antibody on renal allografts in RAT: preliminary report]. PMID- 2263254 TI - Intravenous immunoglobulin. AB - The National Institutes of Health Consensus Development Conference on Intravenous Immunoglobulin: Prevention and Treatment of Disease brought together biomedical scientists in immunology, infectious disease, and pediatrics, as well as health care providers, patients and their families, and the public to address the safe and effective uses of intravenous immunoglobulin (IVIG) preparations. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared a consensus statement. Among their findings, the panel concluded that all currently available IVIG preparations are safe and effective in treating the conditions for which they have been licensed; however, their efficacy in treating other conditions remains to be established. Effective regimens have been developed for primary immunodeficiencies and secondary immunodeficiencies, idiopathic thrombocytopenic purpura, and Kawasaki syndrome. However, optimal dosages and treatment schedules still need to be established for patients who may benefit from IVIG therapy. The panel also concluded that the risks of IVIG therapy are minimal, and adverse events, which are rare, can often be alleviated by reducing the rate or volume of infusion. Future research is also important, particularly studies to discern the mechanisms of action of IVIG, to compare the effectiveness of IVIG preparations, and to determine their long-term effectiveness and their effect on quality of life for patients receiving IVIG. The full text of the consensus panel's statement follows. PMID- 2263255 TI - [The effective method of gene transfer into mammalian cells cultured in vitro]. AB - Efficiency of transformation by a number of vectors with the different selective markers of a set of cell lines has been studied for three different methods based on using calcium phosphate, polybrene, or electroporation. Electroporation is shown to be the most efficient one. Using this method with the system rat2k-cells pAGO vector we have obtained the frequencies of transformation up to 2-3.10(-3). We suggest to use this system as a model for investigation of homologous recombination in the framework of the gene therapy project. PMID- 2263257 TI - German Society for Pharmacology and Toxicology. Abstracts of the second winter meeting. 5-7 December 1990, Hannover. PMID- 2263256 TI - [Conjugation in streptococci]. AB - The problem of conjugation in Streptococci is reviewed as a form of genetical information exchange in bacteria. The theoretical and experimental data of the recent years on the nature, mechanisms and role of conjugation in the spreading of drug resistance in the populations of pathogenic microorganisms are presented. PMID- 2263258 TI - [Actinomyces infection in patients with IUDs]. PMID- 2263259 TI - [Application of fumaric acid derivatives in psoriasis]. PMID- 2263260 TI - [The recommendation 'waiting list problems with mentally handicapped']. PMID- 2263261 TI - [Mourning and grief work]. PMID- 2263262 TI - [Experiences with an electronic network for the clinical consultation of diagnostic imaging material]. PMID- 2263263 TI - [Digital mammography is very useful in mass screening of breast cancer]. AB - Mammograms made between 1981 and 1989 in the Nijmegen screening programme for breast cancer were retrospectively reviewed. Those made before detection of breast cancer showed signs of tumour growth in the place of the subsequently detected malignancy in 22% of the cases. A work station was set up for image digitization and image processing. Display with optimal contrast and image processing of mammograms is possible. Diagnoses based on digitized mammograms displayed on a monitor were as good as those based on the conventional images on film. Automatic detection of image features has been investigated. A procedure for automatic detection of microcalcifications was developed. This research is important for optimalization of diagnosis in screening and because of the expected introduction of direct digital imaging techniques. PMID- 2263264 TI - [Fumaric acid therapy in psoriasis; a double-blind, placebo-controlled study]. AB - Thirty-nine patients with psoriasis (12 females, 27 males) entered a randomised, double-blind, placebo-controlled study on the efficacy of fumaric acid therapy in an outpatient setting. During 16 weeks the patients were treated with tablets containing a combination of dimethylfumarate and different salts of monoethylfumarate, with octylhydrogen fumarate or with placebo tablets. All patients were treated with identical indifferent topical therapy and followed an elimination diet (avoidance of spices, wine and nuts). Thirty-four patients completed the study. Five patients dropped out because of side effects or aggravation of the skin lesions. The patients treated with the combination of monoethyl- and dimethylfumarate showed a significantly better therapeutic response compared with those who were treated with placebo or octylhydrogen fumarate. Side effects of the fumarate containing tablets were flushing, diarrhoea, a reversible elevation of transaminases, lymphocytopenia and eosinophilia. One patient developed a disturbance of the kidney function which normalised after discontinuation of the therapy. PMID- 2263265 TI - [Care in stillbirth; mothers' opinion]. AB - Semi-structured interviews were conducted with 49 women who had experienced stillbirth in 1987-1989. Only 55% were satisfied with the manner in which the first suspicion had been communicated to them, while 85% were satisfied with the communication at the time of the diagnosis. Opinions about care in the labour ward, while largely positive, indicate that lack of tact from an individual may cloud the entire perception of care. Although only 40% had expressed a desire to see the baby, the others were happy to have been persuaded to do so and all were positive about the contact with the dead baby. Of 42 women (86%) who gave consent for autopsy, only one regretted this decision. Support received post partum was considered to be inadequate or insufficient by 10%. Despite the short hospital stay (average 1 day), most women afterwards felt that they would have preferred to return home earlier; only 9% felt that they would have preferred to stay longer. PMID- 2263266 TI - [Grief work an support experienced during abortion and stillbirth]. AB - We investigated by means of a semi-structured, oral interview how women cope with a miscarriage or stillbirth. The need for psychosocial support and the support which was experienced were also studied. The results stress that the mourning process after a miscarriage or stillbirth proceeds in one sense like the 'conventional' mourning process, but differs in some aspects. Women with one or more children show less intense emotions than childless women. The experiences with the professional help and the environmental support differ depending on the moment: before, during or after the bereavement. Negative experiences usually refer to a too businesslike attitude of doctors and nurses in charge, lack of information, shortcomings in the aftercare, clumsy reactions of the environment and unfulfilled needs for contact with other women who had a miscarriage or stillbirth. PMID- 2263267 TI - [Lessons from gynecological-pathological discussions]. PMID- 2263268 TI - [Infections caused by non-diphtheroid corynebacteria]. PMID- 2263269 TI - [Thrombolysis before admission; one link shortened in the chain]. PMID- 2263270 TI - [Long-term results of radial keratotomy]. PMID- 2263271 TI - [Cardiovascular aspects of magnesium]. PMID- 2263272 TI - [Is growth hormone supplementation in growth hormone deficiency in adults indicated?]. PMID- 2263273 TI - [Minor symptoms in family practice; furuncle, carbuncle and furunculosis]. PMID- 2263274 TI - [Physical and psychosocial sequelae of total larynx extirpation and the use of a heat and moisture exchanger]. AB - The incidence and severity of respiratory symptoms after total laryngectomy and their influence on everyday life were studied in 59 patients. Almost all patients (98%) have daily complaints of excessive sputum production and 64% of coughing. More than half the patients (57%) use forced expectoration more than 5 times a day in order to clear the airways and 37% have to clean the stoma more than 5 times a day. Respiratory problems appear to impair the quality of the voice, social contacts and psychological wellbeing and are associated with increased fatigue and sleep problems. In a prospective study the effect of a heat and moisture exchanger (HME) was measured in 42 patients. The frequency of sputum production, forced expectoration to clear the airways and stoma cleaning diminished significantly. As a result, feelings of fatigue decreased and social contacts improved. Respiratory problems after total laryngectomy deserve more attention. Treatment with an HME can in selected cases improve several other physical and psychosocial problems associated with this operation. PMID- 2263275 TI - [Evaluation of the roentgenological and endoscopic diagnosis in malignities of the proximal digestive tract]. AB - During 1968-1988 one endoscopist performed 3154 endoscopic examinations of the upper gastrointestinal tract and detected 400 (13%) malignancies. Endoscopy was indicated in persisting dyspepsia or abnormal findings on X-ray examination of the stomach. In 242 patients earlier subjected to partial gastrectomy 7% stomach cancers were found. No difference existed in the incidence of stomach cancer between patients with either BI and BII gastrectomy. Initially no malignancy was detected in 9 (2.3%) patients. The maximum diagnostic delay was 5 months in these patients. This finding underlines the necessity of a strict follow-up scheme when studying malignancies. PMID- 2263276 TI - [A patient with acute hydroxychloroquine poisoning; recommendation for treatment]. AB - We treated a 30-year-old man for whom Plaquenil (hydroxychloroquine) had been prescribed for rheumatoid arthritis, and who had taken 4 g orally to end his life. Symptoms of severe intoxication due to (hydroxy)chloroquine are rapid onset of hypoventilation, cardiovascular collapse with bradycardia, peripheral vasodilation, arrhythmias and convulsions. The lethal dose of chloroquine has been estimated at 3-5 g in adults and at 0.75-I g in young children. Acute intoxication should be treated with aspiration of gastric contents, artificial ventilation in case of hypoventilation and intravenous or intratracheal dopamine, noradrenaline or adrenaline in case of cardiovascular depression and peripheral vasodilation. Arrhythmias and convulsions should be treated symptomatically. The patient in our case survived the intoxication and is now under psychiatric treatment. PMID- 2263277 TI - [Fetal echography and neural tube defects: morphological diagnosis without clinical certainty]. PMID- 2263278 TI - [Eurothemes. East or West, no health care system is best]. PMID- 2263279 TI - [Valproic acid and stupor]. PMID- 2263281 TI - [In-vitro fertilization from an economic perspective]. PMID- 2263280 TI - [Utilization of a mixture of citrated erythrocytes and heparinized plasma for exchange transfusions]. PMID- 2263282 TI - [The unborn child as patient; recommendations by the Public Health Council]. PMID- 2263283 TI - Writing and using standards of nursing care. AB - This paper outlines some of the background to developments in setting nursing standards in the UK. Many nurses are busily engaged in this activity, and this paper offers a case study of the experience of standard setting in one unit. The Care of the Elderly Unit consists of 162 beds and a 50-place day hospital. Four wards accept acutely ill patients of both sexes, and a further five offer a mixture of rehabilitation and respite care. The buildings are a mixture of old workhouse-type wards and modern purpose-built facilities. A total of 170 nurses are employed in the unit which includes a team of clinical specialists and a senior nurse manager with overall responsibility for the nursing services. Staff at all levels on this team were involved in standard setting. The process of standard setting was an accumulation of eight years' work, with a more intense phase of activity in the last year. A variety of tools have been designed to test out the achievement of the standards. PMID- 2263284 TI - The energy crisis of change. AB - This paper explores the methods that nursing has used to introduce new practice to the clinical environment. The implementation of the nursing process will provide an example of how nursing has attempted to change practice in totality and why the methods used perhaps undermined the original objectives. The use of 'change-agents' and action research to effect change in the ward environment will then be discussed. Particular attention will be paid to the idea of an 'energy crisis'--which may be an inevitable side effect of the change process--and how the programme of development at Ladywell Hospital has taken account of, and acted upon, this problem. PMID- 2263285 TI - Creating a climate for the development of nursing. AB - In this paper, the authors describe the creation of a climate for change and development in the clinical setting. They discuss the emergence of roles of clinical nurse specialist-manager as key practitioner roles in developing the milieu for clinical practice development. The need to build links with education and develop clinical education roles are also explored. In creating a Nursing Development Unit, the authors argue that it is possible to create a setting where innovation can take place, nursing care can be improved, and theory can be put into practice. PMID- 2263286 TI - Implementing a philosophy of care on a children's ward using action research. AB - This paper charts the progress of an action research project initially implemented to assist the staff of a pediatric ward in the development of primary nursing. The use of ward meetings to identify needs and clarify objectives is discussed; from this emerged a broader remit to implement the ward's philosophy of care. Five areas of clinical practice development were identified for work: development of a staff development strategy, identification of resource people, movement to primary nursing, development of standards of care, and development of the ward environment. Progress in these five areas is explored, and the use of evaluation strategies such as visual analogue scales, unstructured interviews and personal diaries are discussed. Description and discussion of some of the difficulties associated with this project are given. In conclusion, the authors address the issue of whether action research is in fact a specific methodology or a philosophy. PMID- 2263287 TI - Education for primary nursing. AB - It is argued in this paper that since practice is context bound, there can be no 'blueprint' offered through a formal educational programme for primary nursing. It is suggested that what may be needed is support on a much broader basis to help nurses to move from the relative safety of traditional approaches to work to the much riskier independent professional model of practice implicit in primary nursing. Three key areas have been identified which could be incorporated within an educational programme, namely development of self as an independent practitioner with the requisite skills of self-directed learning, the ability to accept responsibility discriminatingly and to account for practice through a well established knowledge base; development of interpersonal skills required for the close personal nurse/client relationships required of primary nurses alongside appropriate support mechanisms; an understanding of the context in which practice occurs in order that the broad principles of primary nursing can be adapted to local needs. In this way, people may be helped to move from a dependency on central control and decision-making to become independent creative practitioners who are able to develop a local organisational model which suits their personal situation. PMID- 2263288 TI - Nursing models as philosophies of care. AB - The value of nursing models, especially the well-published works of many of the American theorists, has been debated and argued at length. Indeed the topic was the subject of the July debate at the Royal Marsden Hospital in London, which is an indication itself of the interest post-registration nurses working in cancer care have in the subject. Nurses have talked about using models of care for many years. There are even those who, for example, equate Florence Nightingale's work and writings with a nursing model. I would prefer to interpret Nightingale's work as a nursing philosophy and it is nursing philosophies rather than nursing models that are explored further in the context of cancer in this paper. PMID- 2263289 TI - [The structural characteristics of the dendritic apparatus of transplanted neurons from the embryonic amygdala]. AB - Two main neuronal classes were studied in the grafts of basolateral nucleus of the rat embryonic amygdala stained by the Golgi method--sparsely and densely ramified cells. Transplantation resulted in the increase of dendrite length and ramification of sparsely ramified cells, in the decrease of cell body size and increase of ramification of densely ramified cells. The analysis of polar histograms of the dendritic orientation shows the selective increase of dendrite length and ramification of the both neuronal classes. The dendrites of the intact neurons of basolateral amygdala are distributed almost regularly, they do not display any dominant orientation. After transplantation the main orientation to the area of graft-host integration appears. The changes in dendrites are discussed with respect to the ability of the graft to take part in compensation of the damaged brain functions. PMID- 2263290 TI - [The action of neural transplantation on the brain of rats with a damaged temporal cortex]. AB - Possibilities of transplantation of embryonic brain tissue into the left temporal cortex of the host brain damaged by kainic acid (KA) were investigated. In the group of rats with KA-damaged temporal cortex tissue necrosis and considerable destructions in some structures far from the temporal cortex were revealed. The contralateral hemisphere also had greater area of sections than ipsilateral hemisphere in this group. In the group of rats with viable transplants (T) from E 21 in the temporal cortex damaged by KA the destructions in the same structures and hemisphere asymmetry were negligible, that evidenced for a positive effect of neural transplantation. T from E-15 after its implantation into the cortex of the host brain were pushed out from the cortex on the surface of the brain. These T caused intensification of the negative effect of the KA influence. It was supposed that viable T in the area of the damaged cortex inactivated exciting mediators in this region and also perhaps substituted partly damaged cortex after T had formed connections with the host brain. PMID- 2263291 TI - [The neuronal reactions of the perinuclear zone of the hypothalamic supraoptic nucleus in rats to stimulation of the hypophyseal stalk and the hippocampus]. AB - The orthodromically activated neurons (OAN) were recorded in the hypothalamic supraoptic area under the hypophysial stalk stimulation. They were distinguished by the pattern of the orthodromic activation and the recording sites. More than a half of OAN responded to the stimulation of ventral hippocampus and the responses were primary excitatory in all cases. The similarity in most OAN responses to the hippocampal and the hypophysial stalk stimulation was found. The peculiar influence of the hippocampus on OAN was analyzed, their location in the supraoptic nucleus or perinuclear zone and the supposed morphofunctional connections with the antidromically identified neurosecretory cells being taken into account. PMID- 2263292 TI - [The characteristics of the synaptic reorganization in the sensorimotor cortex of cats after the destruction of the symmetrical portion of the cortex in the opposite hemisphere]. AB - Intracellular recording technique has been used to study reactions of corticospinal neurons (CSN) to stimulation of the ipsilateral ventrolateral nucleus (VLN) of the thalamus in acute experiments on adult intact cats and on cats after lesion on the contralateral sensorimotor cortex (exposition from 6 months to 1.5 years). Acceleration of the monosynaptic EPSPs rise phase in slow CSN was revealed in operated animals, which presumed the reorganization of the synaptic contacts in the SD membrane of flow CSN. Detailed analysis of features and branching of CSN axon, collaterals passing to VLN of the thalamus and participating in formation of the ipsilateral pyramidal tract was made by the method of collision test. The significance of the plastic synaptic reconstruction in the ipsilateral thalamo-cortex reverberating system during the outflow formation under conditions of the partial cortex interhemisphere deafferentation is discussed. PMID- 2263293 TI - [The generation of nonadrenergic inhibiting synaptic potentials in the smooth muscles of the gastrointestinal tract by substituting cesium ions for potassium ions]. AB - Nonadrenergic inhibitory junction potentials (IJPs) evoked by intramural stimulation were investigated in smooth muscle of guinea pig stomach, caecum and colon by means of sucrose-gap method. IJPs disappeared in the smooth muscle preexposed to K-free Krebs solution for 4-9 h and restored by addition 6mM Cs+. The amplitude of IJPs was half as much as one in normal conditions but the latency and duration were significantly prolonged. In most cases apamin blocks IJPs in these muscles. The results presented suggest that IJPs generation is due to Cs+ ions permeated through Ca(2+)-activated apamin-sensitive potassium channels of small conductance in these conditions. As the responses to ATP were affected in parallel with IJPs, these results are consistent with the purinergic hypothesis. PMID- 2263294 TI - [The vestibular nuclei of the guinea pig: their structural and topical organization]. AB - Topographical and cytoarchitectonical organization of the vestibular nuclear complex of guinea pig has been studied. Four vestibular nuclei: superior, lateral, medial, inferior as well as cellular groups (I, F, Y, X, Z) associated with the vestibular nuclei were described on the basis of neutral red stained preparations. The precise delimitation and the stereotaxic coordinates of the vestibular nuclei were performed by means of the analysis of 50 microns thick frontal serial slices treated by glycerine. PMID- 2263295 TI - [The participation of bulbar "respiratory" and "nonrespiratory" neurons in the development of the expiration reflex]. AB - The patterns of impulse activity of medullar neurons were investigated in nembutal-anaesthetized cats during the expiration reflex elicited by electrical stimulation of the internal branch of superior laryngeal nerve. It was shown that low- and high-threshold superior laryngeal afferents caused excitatory reflex reactions of different complexity in significant number of reticular nonrespiratory neurons. Respiratory neurons exhibited systemic changes of spontaneous activity, but in 22.4 per cent of them reflex responses were recorded. These responses occurred during activation of low-threshold laryngeal afferents. Oligo- and polysynaptic excitatory connections of low-threshold laryngeal afferents are found with inspiratory beta neurons, P-cells and laryngeal motoneurons, but inhibitory ones-with inspiratory gamma neurons. Participation of investigated neurons in the mechanisms of inhibition of inspiration, vocal cords closure and rate of breathing adaptive decrease during expiration reflex is discussed. PMID- 2263296 TI - [The effect of noradrenaline on the neuronal reactions of the motor cortex evoked by conditional stimulation]. AB - In chronic experiments on cats the influence of iontophoretic application of adrenomimetic ephedrin and beta-adrenoblocker obsidan (propranolol) on motor cortex neuron reactions following conditional stimuli was investigated under instrumental placing reaction. It was shown for a majority of neurons that the background impulse activity and reactions following conditional stimulation were suppressed by the influence of ephedrin and on the contrary were increased by obsidan application. It is concluded that there exists a consistent tonic suppressing influence of the noradrenergic system on background and evoked cortical neurons impulse activity in the natural state. It is supposed that noradrenergic influence temporal increase may serve as an important link in mechanisms of external inhibition during stress situations, aversive effects, and distractive external excitations. PMID- 2263297 TI - [The short-latency reactions of the limbic cortex neurons to stimulation of the amygdaloid complex]. AB - The extracellular electrical activities of the anterior limbic cortex (LC) neurons to electrical stimulation of amygdaloid central and basolateral nuclei in anesthetized cats was investigated. The orthodromic and antidromic responses of silent-neurons of LC were registered. These results show the existence of short and direct bilateral connections between the anterior LC and different amygdaloid nuclei. It is supposed, that these connections present a "quick-reacting" system, which takes part in the central regulation of the emotional responses. PMID- 2263298 TI - [The depression of the background neuronal activity of the midbrain central gray substance by stimulation of monoaminergic structures]. AB - Three types of neurons which exhibit spontaneous firing were found in the midbrain periaqueductal grey. The stimulation of monoaminergic structures did not change the firing of the first and second types of neurons but suppressed the third one. PMID- 2263299 TI - [The distribution of kainate and quisqualate receptors in the rat cerebellum]. AB - Sensitivity of isolated Purkinje neurons from rat cerebellum to agonists of excitatory amino acids was studied. Kainate and quisqualate activated inward currents in the most studied neurons. NMDA and APB were ineffective. Distribution of kainate and quisqualate receptors was different. Currents activated by kainate and quisqualate were not additive. Hypotheses allowing one to explain the observed results were discussed. PMID- 2263300 TI - [The background impulse activity of the fastigial neurons of the rat cerebellum]. AB - Background impulse activity (BIA) of rat fastigial neurons was studied. Mean frequencies of BIA were 6-130 imp/s (45+5.6 imp/s, n = 105). Monomodality and positive asymmetry of interval histograms were typical of a majority of neurons analyzed. About 1/3 of neurons studied have got Gaussian type of interspike interval distribution. PMID- 2263301 TI - [The role of the higher sections of the brain in the structural-functional hierarchy of the nervous system]. PMID- 2263302 TI - [Perioperative prevention of thromboembolism in neurosurgery]. AB - In neurosurgery, none of the drugs used in other specialties as prophylaxis of thrombo-embolism have found general acceptance. Certain centers reject any drug prophylaxis of thrombo-embolism. Others treat many or--with the exception of subarachnoid hemorrhage--almost all patients according to the Kakkarscheme. Many aim for an individual examination of the risk of early mobilization and, if necessary, combine mechanical and medicinal methods (Tab. 3). No center has published any systematic studies of substantial patient populations. It is not possible to draw any medico-legal conclusions from the neurosurgical literature available. The multitude of diagnostic and therapeutic regimes, sometimes accompanied by contradictory publications, means that even non-neurosurgeons regard neither the diagnosis nor the treatment of thrombo-embolisms as ideal. Even under low-dose heparinization, deep venous thromboses can occur, and it is in principle difficult to refute the contention that this fact changes nothing whatsoever for high-risk patients as far as the incidence of pulmonary embolism ot the occurrence of significant thrombo-embolic events is concerned. Cost calculations have proved that general thrombo-embolism prophylaxis is more expensive than individual thrombosis treatment as necessary (although there are statements to the contrary). It can, however, be stated that additional costs with the aim of improving or maintaining the quality of life would be economically justifiable if a preventive effect were proved. For modern neurosurgery, however, this neither holds true generally nor for a specific subgroup. The state of research would seem to suggest that a prospective, controlled study of neurosurgical patients, primarily in a relatively low-risk group, is necessary, advisable, and justifiable. PMID- 2263303 TI - [Segmental instability and lumbar spinal canal stenosis. Theoretical, clinical and surgical aspects]. AB - Clinical, radiological, surgical and experimental observations make it possible to construct a rational theory of the segmental lumbar instability which explains the pathogenesis of spondylosis, of stenosis and of several cases of disc displacement as well. This theory helps us to choose the right surgical procedure. Spinal stenosis, degenerative spondylolisthesis and some cases of disc displacement are seen as part of a degenerative process with its starting point in regressive changes of the intervertebral disc and lateral joint. This leads to a marked instability of the affected mobile segment. Signs and symptoms of unstable lumbar spine are discussed. In such cases, if decompression of the roots by laminectomy, facetectomy or discectomy is performed without fusion, the consequences are usually treated but not the main cause of the trouble, namely the instability. Finally, we describe a procedure which we prefer as the safest and best of all, using selected decompression by means of joint screws (spondylodesis) as suggested by F. Magerl (41-44). PMID- 2263304 TI - [Radical approach in lumbar intervertebral disk operations]. AB - A study of a postmortem preparation of a surgical model of lumbar discectomy serves as basis for discussing whether radical "clearing out" of the intervertebral space is at all possible or meaningful. The degree of radicality depends upon the extent of degeneration of the disc, involving a more or less extensive resection of the anulus fibrosus. The weak point of the operative procedure is mostly the dorsomediolateral area contralateral to the site of the approach. PMID- 2263305 TI - [Evaluating performance in lumbar intervertebral disk damage following chemonucleolysis]. AB - In spite of the good or excellent long-term results in 60% to 80% of the cases reported in the literature, the efficacy of the less invasive percutaneous nucleolysis in the treatment of therapy-resistant lumbar compression of the nerve root in patients with lumbar disk protrusion still remains controversial. On the one hand, there is discussion about the actual effectiveness of the enzymes injected and their local activity in bringing about the desired long-lasting nerve-root decompression. On the other hand, the presumed advantage of he method is questioned. It is said that postoperative morbidity is decreased and shortened, and that job rehabilitation is faster, especially with people performing hard physical work. More recently, the same can be said for the much vaunted method of percutaneous automated diskectomy and nucleotomy. It was only possible to use these less invasive treatment techniques with approx. 10% of the author' patients with therapy-resistant lumbar compression syndromes of the nerve root caused by disk protrusion. In 85% of all patients treated, CNL produced a good or satisfactory result as regards the relief of sciatica and neurological disturbances. These long-term results cannot be transferred to job-rehabilitation results, as a critical review of 133 cases has shown. The authors were able to examine 108 of the 133 patients approx. one year after nucleolysis. In the group of businessmen, government officials, white-collar workers, and students, there was a correlation between long-term neurological results and job rehabilitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263306 TI - [Chemonucleolysis with chymopapain in lumbar disk hernia. Randomized comparative study with operated patients]. AB - We carried out a randomized comparison study with 69 patients, one group of whom had been operated on (41) and the other group treated by chemonucleolysis with chymopapain (25) in order to arrive at an objective picture of the latter recently much criticised method. 88% of the patients who were treated with chymopapain showed lasting success, and almost 90% of the operated patients are also in a good condition. In our opinion, complications can be avoided and the patient can be spared a surgical operation by the correct choice of patients and proper performance of the method in standby anaesthesia. This justifies the performance of chemonucleolysis with chymopapain. PMID- 2263307 TI - Haemodynamic changes in patients with subarachnoid haemorrhage assessed by Tc99m labeled albumin microspheres. AB - The aim of the present study was the investigation of haemodynamic changes in the brain in patients after subarachnoid haemorrhage (SAH) using Tc 99 m labelled albumin microspheres (LMS). Twenty-nine patients after SAH (13 in the acute and 16 in the chronic stage of the disease) and four neurologically healthy subjects were examined. LMS were injected in the carotid during angiography and brain and lung scintigrams were taken using gamma camera. In the control subjects a diffuse and uniform distribution of the activity in the brain was found. In the patients with acute SAH "patchy", nonhomogenous distribution of the activity was found, ranging up to the regional absence of perfusion. This pattern was observed in the chronic stage as well, but less obvious than in the acute. In all the patients the evident trapping of LMS in the lungs was demonstrated confirming brain shunts, absent in the control group. By measuring the activity in the brain and lungs after intracarotid injection of LMS, haemodynamic changes in the patients after SAH were proved and the existence of brain shunts was demonstrated. It seems that shunts are functional anastomoses and important protective mechanism, opening when cerebral haemodynamics is altered. PMID- 2263308 TI - Local treatment of spasmodic torticollis with botulinum toxin. AB - Fifteen patients with spasmodic torticollis were treated with local injections of botulinum--A toxin. All the patients were followed for a period of 4 to 7 months. Thirteen out of 15 patients (86%) improved in the amount of sustained movements of torticollis. In six out of 9 patients presenting with pain complete relief was noted. Beneficial effects of botulinum toxin injections lasted from 2 to 3 months, with reproducible efficacy after repeated injections. The most frequent side effect was dysphagia, presented in 10 patients. PMID- 2263309 TI - Gender differences in the associated complications among type-II diabetics with peripheral neuropathy. AB - Diabetic neuropathy is an intriguing problem both for the patient and the clinician, however the clinical characteristics of type-II (non insulin dependent) diabetics with peripheral neuropathy with special reference to gender differences is not paid much attention. We studied peripheral neuropathy and related complications in 179 type-II diabetics. Peripheral neuropathy was noted in 46 of 111 men and in 46 of 68 women. The age group of subjects did not differ significantly. Duration of diabetes differed between the groups with (n = 46) and without (n = 65) peripheral neuropathy (expressed in years and as mean +/- S.E: 7.7 +/- 0.7 vs 5.5 +/- 0.7; t = 2.2; P less than 0.05) in men, whereas in women it was not significant. Higher proportion (62.5% of 24) of men with proteinuria had neuropathy. Similar findings in women were not different. We conclude i) a large percent (51.4%) of the type-II diabetics had peripheral neuropathy than realised ii) duration of diabetes and proteinuria are important risk factors associated with neuropathy especially in men and iii) the gender differences need further clinicopathologic evaluation. PMID- 2263310 TI - [Common migraine--diagnostic criteria]. AB - The characteristics of common migraine are not unique, they also appear in other forms of benign headaches. As there are no laboratory tests and biological signs enabling the diagnosis of migraine and its differentiation from the headache due to muscle contractrion, clinical criteria which are simplified and easy to comprehend should be used. We compared the symptoms in 29 patients of both sexes, suffering from common migraine, as well as 29 patients with headache due to muscle contraction (chronic daily headaches). In common migraine the following symptoms appear in greater percentage (statistically significant): nausea, vomiting, unilateral localization of pain, pulsating pain, photophobia and phonophobia. Bad headache is more frequent in patients with common migraine than in those suffering from chronic headache. We should accept Solomon's and Cappa's attitude who suggest at least two of the following five criteria: 1. nausea with or without vomiting, 2. unilaterality, 3. pulsating pain, 4. photophobia or phonophobia, and 5. provocation by menstruation or positive family history. Besides the above mentioned criteria the authors also mention and emphasize the existence of free interval in migraine when the patient has no difficulties and feels well. PMID- 2263311 TI - Non-surgical treatment of the solitary brain abscess in children. AB - In a ten year old girl with operated congenital heart defect: pulmonary stenosis, a solitary brain abscess developed in the right frontotemporal region after teeth extraction. The clinical disease was manifested with fever, headache and by tonic epileptic seizure of the grand mal type dominating on the left side. Suspicion of the abscess existence has been raised on the basis of the EEG finding and proved by the brain CT scan. Agent has not been identified, most probably due to antibiotic therapy applied prior to admission. We decided for the antibiotic treatment with benzilpencillin (500,000/kg/day), chloramphenicol (50 mg/kg/day) cloxacillin (130 mg/kg/day) intravenously during 4 weeks. Clinical improvement of the condition, the EEG and CT findings occurred two weeks after the beginning of the therapy. After a month further marked improvement of the EEG findings occurred as well as the disappearance of the abscess cavity. Three months after the completed therapy the control EEG and the brain CT scan were normal. The girl having been followed up for three years is growing normal and has completely normal neurologic findings. PMID- 2263312 TI - [The Miller-Fisher syndrome (clinical report)]. AB - The authors present a case report of two female patients, aged 16 and 33. Both patients had the same sudden onset of illness, with diplopia and nystagmus and very severe ataxia. The younger patient had absent tendon reflex, while the older one had the tendon reflex preserved. The younger patient had the triparesis present, both patients had no sphincter disorders. They did not have sensibility disturbances, except that the younger patient had hypesthesia of the soft palate (the motor function was preserved). The first patient was somnolent at the beginning. The clinical course being favourable, the younger patient recovered faster than the older one. Electoencephalogram was normal in both patients. CT of the brain was changed at one moment, locking like inflammatory changes. CSF of the younger patient, done twice, was normal. Serologic findings on viruses were normal. Electromyography in both patients showed, beside good motor velocity, the marked sensory velocity which recovered at the control check-ups. The authors present these two cases and they consider the differential-diagnostic difficulties of Fisher's syndrome compared to "brain stem encephalitis". PMID- 2263313 TI - The influence of radiotherapy and chemotherapy on cerebral metastases. AB - A group of 110 patients (68 male and 42 female) with cerebral metastases, treated at the Institute of Clinical Oncology and Radiotherapy, Zagreb University School of Medicine, during the period 1978-1984, were included in the study. Most patients were aged 50-60 years. Out of 110 patients, 52 were treated by radiotherapy and 58 by radiotherapy plus chemotherapy. Metastases from the bronchus carcinoma, breast carcinoma, melanoma and gastrointestinal carcinoma were present in 59%, 21.8% and 4.6% of patients, respectively. In 1.8% metastases from hypernephroma and in 3.6% from other malignant tumors were observed. In 4.6% cases, the origin of metastases could not be identified. Fifty-two out of 110 patients were treated by radiotherapy alone. They received 3000 cGy in 8-10 fractions, to the whole brain, with two parallel opposed fields. Fifty-eight out of 110 patients treated with radiotherapy and chemotherapy were given the same radiotherapeutic treatment. Chemotherapeutically, they were treated with BCNU and CCNU with or without Vincristin in standard doses. In the group of 52 patients treated by radiotherapy alone the median survival was six months (1-16 months), i.e. the same as in the group treated by both radiotherapy and chemotherapy (1-26 months). PMID- 2263314 TI - Monocyte-mediated entry of pathogens into the central nervous system. AB - The origin of the microglia has long been a subject of debate. However it is now clear that monocytes enter the normal central nervous system and follow a series of morphological transformations as they differentiate into microglia. Thus, microglia are of monocytic origin. Since monocytes migrate into the normal CNS, they represent potential vehicles for the entry of pathogens into the nervous system and indeed may carry particulate matter into the CNS. Both viruses and bacteria use this 'Trojan horse' mechanism of entry in the pathogenesis of CNS disease. PMID- 2263315 TI - Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. AB - In order to test the hypothesis that the immune system plays a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), the cellular composition of the spinal cord inflammatory infiltrate was analysed in eight cases of sporadic ALS by a panel of monoclonal antibodies. The majority of the many diffusely scattered lymphocytes seen in the anterior and lateral corticospinal tracts and anterior horns belonged to the suppressor/cytotoxicity T-cell subset and were admixed with variable numbers of macrophages. Helper-inducer T-cells were rare and B-cells were conspicuously absent. Compared to controls, ALS specimens exhibited an increase in major histocompatibility complex (MHC) products or human leucocyte antigens (HLA) in the corticospinal tracts and anterior horns. HLA-ABC antigens were expressed in the honeycomb pattern of the glial matrix of the spinal cord, and HLA-DR antigens were strongly expressed by large dendritic cells. In addition, macrophages and endothelial cells were labelled by HLA-DR. These findings suggest that an autoimmune process or infectious agent may play a role in ALS. PMID- 2263316 TI - The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze-killed nerve grafts. AB - The ability of long acellular nerve grafts to support axonal regeneration was examined using inbred rats. Grafts (40 mm long) of tibial/plantar nerves were used either as live grafts or after freeze-drying to render the grafts acellular. The grafts were sutured to the proximal stump of severed tibial nerves in host animals which were then killed 1-12 weeks later. Axons rapidly regenerated through the living grafts but only extended 10-20 mm into the acellular grafts. This distance was achieved by 6 weeks and thereafter no significant further axonal extension occurred in the acellular grafts. A few naked axons lacking Schwann cell contact were identified in all acellular grafts, but became more numerous near the distal extent of axonal penetration into 6-12 week grafts. These axons contained large numbers of neurofilaments. When the distal 20 mm of 6 week acellular grafts (segments into which axons had not penetrated) were sutured to freshly severed tibial nerves, axons grew readily into the grafted tissue to a maximum distance of 9 mm. It is therefore likely that the limits to axonal regeneration through initially acellular grafts were set by factors intrinsic to the severed nerve. It is suggested that the limited migratory powers of Schwann cells may be one such factor. The concept that basal lamina tubes are not essential for axonal regeneration but may act as low resistance pathways for both axonal elongation and Schwann cell migration is discussed. PMID- 2263317 TI - The use of monosodium glutamate in identifying neuronal populations in mice infected with scrapie. AB - The excitatory amino-acid, monosodium glutamate, which causes degeneration in the retinal ganglion cells in neonatal mice, was used to investigate the transport of scrapie within optic nerve axons. In treated mice, there was prolongation of the incubation period following intraocular infection with the ME7 strain of scrapie, and a decrease in the severity of retinopathy after intracerebral infection with the 79A strain. These data confirm that scrapie infection spreads along neural pathways, and demonstrate the potential use of selective neurotoxins to study pathogenesis. PMID- 2263318 TI - Non-missile head injury: report of a patient surviving for 6 years. AB - A female patient with non-missile head injury is described. She showed slight improvement in her level of consciousness, and survived for 6 1/2 years after injury. At autopsy, the white matter lesions were localized rather than diffuse in distribution. In addition to lesions in the corpus callosum, anterior commissure and dorsolateral quadrant of the rostral brain stem, those in the parasagittal cerebral white matter, and in the hilus of the dentate nucleus and superior cerebellar peduncle were considered to be due to primary axonal injury. A cavity in the frontal white matter was remarkable in that there was no evidence to indicate expansion of the lesion due to haemorrhage. These features suggested that the injurious physical forces had acted parallel to the direction of the axons. PMID- 2263319 TI - Spike-and-wave neocortical patterns in rats: genetic and aminergic control. AB - Spontaneously occurring and drug-induced high voltage spike-and-wave electroencephalogram patterns were examined in inbred rats of the Fischer 344 and Buffalo strains and of the random-bred Sprague-Dawley strain at different ages. In addition, tyrosine hydroxylase activity and dopamine D2 receptor density were determined in the substantia nigra, corpus striatum, olfactory tubercle and ponsmedulla areas of Fisher 344 and Buffalo animals. High voltage spike-and-wave episodes were present in 87.5% of the 3-month-old and in 100% of the older Fischer 344 rats. High voltage spike-and-wave episodes were completely absent in 3-month-old Buffalo and Sprague-Dawley animals but could be induced by systemic injection of pentylenetetrazol and at an older age they appeared in 58.3% (12 month) and 71.4% (greater than 26-month) of the subjects of these strains. The incidence and duration of high voltage spike-and-wave episodes were significantly higher/longer in Fischer 344 rats than in the age-matched Buffalo and Sprague Dawley animals. The dopamine blocker acepromazine induced a several-fold increase of the incidence and duration of high voltage spike-and-wave episodes in 3-month old Fischer 344 rats, but failed to induce high voltage spike-and-wave episodes in Buffalo animals at this age. However, acepromazine also triggered high voltage spike-and-wave episodes in Buffalo rats when they were pretreated with subthreshold doses of pentylenetetrazol. Tyrosine hydroxylase activity was significantly higher in the substantia nigra, corpus striatum and olfactory tubercle of the Fischer 344 strain than in Buffalo rats. The higher tyrosine hydroxylase activity was paralleled with significantly higher D2 binding values in the corpus striatum and olfactory tubercle of Fischer 344 rats. These findings suggest that the neocortical high voltage spike-and-wave phenotype is genetically mediated and that the inbred Fischer 344 and Buffalo rats with defined bilineal origin will facilitate future works aimed at the identification of genetic elements involved in the generation of neocortical high voltage spike-and-wave episodes. The significant genotype x age interaction supports the suggestion, however, that high voltage spike-and-wave episodes are likely to be influenced by more than one gene; some of them are probably related to the regulation of brain aminergic systems. PMID- 2263320 TI - The effect of [Met]enkephalin on the periaqueductal gray neurons of the rat: an in vitro study. AB - Intracellular and extracellular recording techniques and in vitro preparation were used to examine the effect of [Met]enkephalin on the rat periaqueductal neurons. In the 20 cells that were recorded intracellularly, [Met]enkephalin caused an increase in the resting membrane conductance, hyperpolarization of the cell membrane, an increase in the firing threshold and a decrease in the spontaneous firing rate. This effect of [Met]enkephalin could be blocked by naloxone. The effect of [Met]enkephalin on 99 neurons was also examined using extracellular recording. In 59% of cells, pressure application of [Met]enkephalin caused a dose-dependent inhibition that could be blocked by naloxone; 15% of the cells were excited and the remaining neurons (26%) did not respond. Nineteen per cent of responsive cells were located in the dorsolateral subdivision; 41% in the ventrolateral and 13% in the dorsal regions. In 10 cells, perfusion with physiological saline solution/Mg did not alter the inhibitory effect of [Met]enkephalin. However, perfusion with physiological saline solution/Mg abolished the excitatory response to [Met]enkephalin in four cells. It is concluded that: (1) the major effect of [Met]enkephalin on periaqueductal gray cells is inhibition that occurs through a direct postsynaptic process. This inhibition is probably due to an increase in permeability to potassium; (2) a small population of periaqueductal gray cells are excited by [Met]enkephalin, probably through a presynaptic process. PMID- 2263321 TI - Transneuronal degeneration in the midbrain central gray following chemical lesions in the ventromedial nucleus: a qualitative and quantitative analysis. AB - In the preceding experiments with electrolytic lesions of the ventromedial nucleus of the hypothalamus, we showed pre- and postsynaptic degeneration in the midbrain central gray of the rat. The postsynaptic degeneration seen may indicate a transneuronal effect of the ventromedial nucleus on the midbrain central gray. Electrolytic lesions, however, destroy afferent endings and fibers in passage, so that the postsynaptic degeneration seen in the midbrain central gray may be due to retrograde degeneration of midbrain central gray afferents to the ventromedial nucleus or due to degeneration of fibers in passage. In order to distinguish among these possibilities, chemical, i.e. kainic acid and N-methyl aspartate, lesions were made in the ventromedial nucleus and the ultrastructure of the midbrain central gray and cerebral cortex was examined at various intervals following the lesions. Both of these excitotoxins have been shown to destroy neurons, sparing afferent terminals and fibers in passage. Animals receiving kainic acid lesions in the right ventromedial nucleus were allowed to survive for one week, and animals receiving N-methyl aspartate lesions in the right ventromedial nucleus were permitted to survive for four, eight, and 20 days. Midbrain central gray tissue of unlesioned animals served as a control for both kainic acid and N-methyl aspartate lesions. In addition, other control animals received injections of the same amount of N-methyl aspartate in the right parietal cortex and were permitted to survive for four and eight days. For each of the above injection and survival conditions, the left cortex and subdivisions of the midbrain central gray were removed and processed for electron microscopy. Animals receiving ventromedial hypothalamic lesions with both kainic acid and N methyl aspartate showed signs of pre- and postsynaptic degeneration. A quantitative analysis (General Linear Model Procedure) of degeneration was performed on the cortex and midbrain central gray of animals receiving N-methyl aspartate lesions in the ventromedial nucleus and cortex, and several parameters were measured. Animals receiving ventromedial hypothalamic lesions and surviving for eight and 20 days show significantly higher ratios of degenerating presynaptic elements to total presynaptic elements, degenerating postsynaptic elements to total postsynaptic elements, and degenerating total elements to total elements, in the midbrain central gray than in the cortex. Furthermore, the ratio of degenerating postsynaptic elements to total postsynaptic elements is larger than the other ratios.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2263322 TI - Tuberal supraoptic neurons--II. Electrotonic properties. AB - The electrotonic properties of tuberal supraoptic neurons were studied from conventional intracellular recordings made in the hypothalamo-neurohypophysial explant in vitro. The cable parameters electrotonic dendritic length, and the dendritic to somatic conductance ratio, were estimated using the slopes and intercepts of the first two peeled exponentials of the voltage transients generated by current steps. The estimations were made assuming an equivalent cylinder model consisting of a soma and an attached, lumped dendrite of finite length. An equalizing time constant was resolved in 12 of 17 neurons, allowing calculation of both cable parameters. In only one of these 12 was it necessary to assume a somatic shunt to account for the data. The average value of the dendritic electrotonic length was 1.02, and that of the dendritic to somatic conductance ratio, 4.11. In the remaining five neurons, an equalizing time constant could not be peeled and consequently the dendritic cable parameters could not be estimated. The average input resistance of these 12 neurons was 162 M omega and the average membrane time constant was 11.86 ms. Principal Components Analysis revealed that the variance of input resistance and time constant was largely explained by one factor, while that of dendritic electrotonic length and the dendritic to somatic conductance ratio was explained by a separate, independent factor, suggesting a separation of electrical and morphological parameters, respectively. In addition, the variability of the data indicates that considerable differences in the morphology and specific membrane resistivity exist across supraoptic neurons. An analysis of spontaneously occurring postsynaptic potentials revealed that the shapes of these potentials could not be explained simply by assuming that they were determined by their passive decay from some point along the equivalent cable to the soma. In conclusion, dendrites make a significant and previously unappreciated contribution to the electrotonic behavior of supraoptic neurons. These electrotonic properties are similar to those of many other, morphologically diverse, central nervous system neurons. PMID- 2263323 TI - Target-related patterns of co-existence of neuropeptide Y, vasoactive intestinal peptide, enkephalin and substance P in cranial parasympathetic neurons innervating the facial skin and exocrine glands of guinea-pigs. AB - The patterns of co-existence of neuropeptides in cranial autonomic neurons of guinea-pigs have been examined with quantitative double-labelling immunofluorescence and retrograde axonal tracing using Fast Blue. Within the sphenopalatine, otic, sublingual and submandibular ganglia, and a prominent intracranial ganglion associated with the glossopharyngeal nerve, most neurons contained immunoreactivity of vasoactive intestinal peptide, neuropeptide Y, enkephalin and substance P in combinations that were correlated with their projections. Hair follicles in the facial skin formed a major target of sphenopalatine ganglion cells. The combinations of peptides co-existing in these neurons depended upon the region of the skin where the follicles were located. The parotid gland was innervated by neurons with cell bodies in the otic ganglion or the intracranial ganglion. Most of these neurons contained immunoreactivity to all four peptides. The sublingual gland was innervated by local ganglion cells usually containing immunoreactivity to neuropeptide Y, vasoactive intestinal peptide and substance P. The submandibular gland was innervated by local ganglion cells containing enkephalin immunoreactivity and low levels of immunoreactivity to neuropeptide Y. Presumptive vasodilator neurons, containing immunoreactivity to vasoactive intestinal peptide but no other peptide examined here, comprised less than 10% of cranial autonomic ganglion cells. These results demonstrate that the patterns of co-existence of neuropeptides in cranial autonomic neurons show a high degree of target specificity. The discovery that hair follicles form a major parasympathetic target implies a broader range of actions of cranial autonomic neurons than has been suspected until now. PMID- 2263324 TI - Clinical evaluation of the ITI (F-type) hollow cylinder implant. AB - In 1976 the hollow cylinder implant was introduced. A number of articles have been published about the ITI implant system. In this article, short-term results of 102 ITI F-type implants in 40 patients are reported. The results showed this one-stage implant to be at least comparable to other well-known implant systems. PMID- 2263325 TI - Massive osteolysis of the maxillofacial bones. Report of two cases. AB - Two cases of massive osteolysis were encountered, one affecting the mandible and the other the maxilla and mandible. Only 13 cases have been reported so far in the existing literature for massive osteolysis of the mandible. It is indeed a rare disease. Our two cases were surgically treated and were clinically and histopathologically assessed. PMID- 2263326 TI - Coronoid process elongation in rhesus monkeys (Macaca mulatta) after experimentally induced mandibular hypomobility. A cephalometric and histologic study. AB - The present study provided an experimental model that allowed a cephalometric and histologic analysis of craniofacial growth in monkeys with induced translatory impairment of the mandibular condyle. Cauterization was performed anterior to the joint in nine experimental rhesus monkeys, while eight animals served as control subjects. The experimental procedure produced mandibular hypomobility in six animals, in three by means of temporomandibular joint ankylosis and in three by means of dense scar tissue formation anterior to the joint. In the remaining three experimental animals no restriction of mandibular mobility was created. Mandibular hypomobility was found to induce elongation of the coronoid process and was also associated with bone deposition in the gonial region. In contrast, normal remodeling of the gonial region was found in the experimental animals with normal range of movements and in the control animals. PMID- 2263327 TI - Dysgeusia, gustatory sweating, and crocodile tears syndrome induced by a cerebellopontine angle meningioma. AB - Facial nerve involvement in cerebellopontine angle tumors, both during their development and after excision, may be expressed in irreversible dysfunction of the parasympathetic pathways. The exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components. This report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma. She had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area. Occult ipsilateral hyposalivation and hypolacrimation were diagnosed. In patients with seventh and ninth cranial nerve pathoses, evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae. PMID- 2263329 TI - Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. AB - In this clinical study at the University of Texas M. D. Anderson Cancer Center, unstimulated and stimulated salivary flow rates were obtained from 47 patients with head and neck cancer who had received mantle, unilateral facial, or bilateral facial field radiotherapy from 0.5 to 25 years earlier. The magnitude of salivary flow rate reduction compared with a healthy control group was primarily related to the radiation dosage and the amount of salivary gland tissue included in the irradiated fields. Flow rates were lower for women in all groups, but these differences were not statistically significant. PMID- 2263328 TI - In vitro effect of chlorhexidine and amikacin on oral gram-negative bacilli from bone marrow transplant recipients. AB - Prophylactic use of chlorhexidine (CHX) mouthrinses has been shown to benefit the oral health status of bone marrow transplant recipients and other immunosuppressed persons and to reduce systemic complications of oral origin. However, a problem that often emerges with these patients is oropharyngeal and lower respiratory tract colonization by opportunistic aerobic or facultative gram negative bacilli (GNB). Trends in four studies indicated that CHX rinses may predispose these persons to oral colonization by GNB such as the enterobacteria, Klebsiella pneumoniae and Enterobacter cloacae. Since GNB are generally susceptible to broad-spectrum aminoglycoside antibiotics such as amikacin, the in vitro sensitivities of K. pneumoniae, E. cloacae, Pseudomonas aeruginosa, and Escherichia coli ATCC reference strains and K. pneumoniae and E. cloacae oral clinical isolates to combinations of CHX and amikacin were determined by means of a disk diffusion sensitivity assay on Mueller-Hinton agar. The amikacin minimum inhibitory concentrations for all GNB tested were much lower (less than or equal to 4.69 to less than or equal to 9.37 micrograms/ml) than those for CHX (less than or equal to 18.75 to less than or equal to 300 micrograms/ml), and combinations of CHX and amikacin gave larger growth inhibition zones than CHX alone. No antibacterial antagonism between CHX and amikacin was found, and their solubilities were compatible. Therefore use of topical amikacin in conjunction with CHX rinses may reduce oral colonization by GNB in severely immunocompromised patient populations. PMID- 2263330 TI - Blood pressure measurements during dental checkups representative of 26-hour registration. AB - The effect of dental checkups on blood pressure was investigated. In 27 normotensive patients (13 men and 14 women) aged 22 to 64 years (mean 39.75 +/- 10.5 years), a 26-hour continuous, noninvasive blood pressure registration was carried out. Of each patient at least 175 blood pressure measurements were registered during these 26 hours, giving a total amount of 4725 blood pressure measurements. A dental checkup appointment with the family dentist was included. Blood pressure values displayed the well-known diurnal variation, but the visit to the dental surgeon was not accompanied by a rise in blood pressure. There was no significant difference between the blood pressure values during the 26-hour period and those during the checkup period. During a rest period after the dental checkup, neither the systolic nor the diastolic pressure fell to any degree in relation to the 26-hour values or the visit to the surgeon. PMID- 2263331 TI - Lack of evidence for link between intradental lesions and chronic renal failure. AB - In at least three publications, radiographic intradental changes have been mentioned in connection with end-stage renal failure with and without renal osteodystrophy. The influence of immunosuppressive therapy has been suggested. In 63 patients with one or a combination of the above-mentioned criteria, no evidence was found on intradental radiolucencies or of extreme narrowing (obliteration) of the dental pulp cavity. PMID- 2263332 TI - Recurrent peripheral facial nerve palsy after dental procedures. AB - Peripheral facial palsy is an uncommon complication of dental procedures. Most cases begin immediately after dental anesthesia and resolve within 12 hours. No report of recurrent facial palsy with dental manipulations has previously been described. We report a patient with two episodes of peripheral facial palsy, 2 years apart, developing within 24 hours of dental procedures. A third episode of contralateral facial weakness developed 3 years after the second event. This event was not related to dental manipulations. Although the exact mechanism is not known, dental manipulations may rarely result in precipitation of recurrent Bell's palsy. PMID- 2263333 TI - Dexamethasone as an adjunct in oropharyngeal obstruction in a patient with leukemia. AB - Incipient airway obstruction due to fulminating bacterial infection of pharyngeal tissues requires prompt and definitive intervention. A case is presented in which dexamethasone was a key adjunct to antibiotic therapy in averting this problem in a severely neutropenic patient with acute leukemia. PMID- 2263334 TI - Gingival and cutaneous xanthomatosis associated with primary biliary cirrhosis. Report of a case. AB - The first comprehensive case report of intraoral xanthomatosis associated with primary biliary cirrhosis is detailed. The lesions were present along the free gingival margin and labial vestibule. Crevicular fluid was noted to be tinged yellow. Generalized cutaneous eruptions were also seen. The xanthomas were attributed to the underlying hyperlipoproteinemia. Advanced progression of the hepatic disease necessitated a liver transplant. Disappearance of both oral and skin lesions were subsequently observed. PMID- 2263335 TI - Subacute necrotizing sialadenitis. AB - Twelve cases of a heretofore unreported minor salivary gland disease have been reported. Although an infectious cause is suspected for this self-limiting inflammatory process, the actual cause remains unknown. It typically presents as a unilateral, erythematous, nonuclerated but painful, solitary firm swelling of the posterior hard palate. Patients are most often young white men who have spent several weeks in a new environment with a group of people living in close quarters such as military barracks. PMID- 2263336 TI - African Burkitt's lymphoma: case report and light and electron microscopic findings. AB - An African Burkitt's lymphoma occurred in a 9-year-old American boy who had jaw tumors, proptosis, and abdominal masses. Histologically, the tumor consisted of a monotonous overgrowth of undifferentiated lymphocytes with a "starry sky" appearance. The differential diagnosis of African versus American form and Burkitt's lymphoma versus non-Burkitt's lymphoma is discussed. PMID- 2263337 TI - Intramuscular hemangioma in the oral region: report of three cases. AB - The occurrence of intramuscular hemangioma in an intraoral or perioral localization is rare, and a thorough knowledge of these tumors is necessary for adequate diagnosis and treatment. Three cases are presented with discussion, and their histopathology and differential diagnosis are discussed. An adequate primary excision is necessary to avoid recurrence. PMID- 2263338 TI - The potential of periodontal pocket formation associated with untreated accessory root canals. AB - Teeth that were to be extracted because of periodontic-endodontic involvement, in six patients, were treated by hemisection or root amputation. The roots were processed histologically. All cases showed the presence of accessory root canals with remnants of pulpal tissue, bacteria, and necrotic debris. It was demonstrated in the cases studied that residual necrotic tissue in untreated root canals can result in periradicular pathosis. We may speculate that if the inflammatory process persists and drainage results via the sulcus, in time, plaque and then concretions may develop. PMID- 2263339 TI - Reactions of rat odontogenic tissues to heat. AB - Twenty-four Wistar rats were anesthetized and 200 degrees C heat was applied for 4 minutes to each mandibular left first molar. Eight of these rats were then killed at 2, 8, and 14 weeks. The subject and control teeth were radiographed and compared. They were then prepared for histologic evaluation and scored for levels of inflammation in both the pulpal and periradicular tissues. Furcal, interproximal, and apical radiographic changes were found at all three time intervals. These changes involved progressively larger percentages of teeth at 8 and 14 weeks. Histologically, complete necrosis and/or abscess formation were found in the coronal portions of all experimental pulps. With time, inflammatory changes increased in intensity and progressed through the radicular pulps, resulting in necrosis or calcific changes and, finally, inflammatory changes in the periradicular areas. The pathosis created by the application of heat was devoid of microorganisms as evaluated by the Brown and Brenn stain. PMID- 2263340 TI - A film-holding device to facilitate endodontic radiography. PMID- 2263341 TI - A retrospective clinical study of endodontically treated mandibular incisors in a selected Chinese population. AB - Clinical studies of incidences of the number of canals in human teeth should correlate with the percentages obtained in laboratory samples. In this study the incidence of two canals in the mandibular incisors was compared with figures obtained from in vitro extracted teeth, as well as from one clinical study. A very low percentage was obtained from the examination of clinical records, and this could be due to racial differences in the samples examined. PMID- 2263342 TI - The antimicrobial effect of various endodontic sealers. AB - The antimicrobial activity of an endodontic sealer can be helpful in destroying any remaining root canal microbes. Therefore it was decided to test the antimicrobial activity of several commonly used endodontic sealers. The sealers used were Grossman's sealer, Tubliseal, Calciobiotic, Sealapex, Hypocal, eucapercha, Nogenol, and AH26. Also tested were dry calcium hydroxide powder, calcium hydroxide mixed with saline, and a Teflon formulation. The microbes used were Streptococcus mutans (a gram-positive microaerophile). Staphylococcus aureus (a gram-positive facultative anaerobe), and Bacteroides endodontalis (a gram negative obligate anaerobe). The freshly mixed sealers were placed into the prepared wells of agar plates inoculated with the test microorganisms. After varying periods of incubation, the zones of inhibition of bacterial growth were observed and measured. Grossman's sealer had the greatest overall antibacterial activity. However, AH26 had the greatest activity against B. endodontalis. The zinc oxide-eugenol-based sealers had more antimicrobial activity than either the calcium hydroxide-based sealers or eucapercha. PMID- 2263343 TI - Cross-sectional tomography. A diagnostic technique for determining the buccolingual relationship of impacted mandibular third molars and the inferior alveolar neurovascular bundle. AB - Twenty-two patients with 31 impacted mandibular third molars were examined with a new, precise, cross-sectional tomographic technique to assess the radiographic size, shape, branching pattern, location, and degree of cortication of the mandibular canal, and the inclination of impacted mandibular third molars in the buccolingual plane. The mandibular canal, including bifid canals, was accurately identified in 30 cases (96.8%). The cross-sectional appearance of the canal was an uncorticated, or partially corticated, radiolucent oval that measured on average (+/- SD) 2.9 +/- 0.7 x 2.5 +/- 0.6 mm in diameter. It was located more frequently (45.2%) on the buccal aspect of the impacted mandibular third molar. About 60% of the mandibular canals notched the inner cortical plate of the mandible or the third molar root surface. Cystic expansion and quantification of cortical bone destruction were readily assessed by this technique. It was concluded that diagnostic information obtained from cross-sectional tomograms significantly aids the oral and maxillofacial surgeon during the preoperative diagnostic workup and that the radiation risks are comparable to those of other accepted localization techniques. PMID- 2263344 TI - Effect of environmental factors on film badge dosimetry readings of dental office personnel. AB - Inadvertent exposure of film badges to environmental factors may produce fogging of the film and yield higher radiation exposure readings. Common environmental factors in everyday living were studied to assess their effect on film badge readings. Only heat appeared to have any significant effect, because moisture, chemicals, pressure, cold temperature, and non-work-related electromagnetic radiation did not substantially alter film badge readings. Therefore not all unexplained high readings on personnel film badge reports may be due to heat or other common environmental factors evaluated in this study. PMID- 2263345 TI - Radiculomegaly of canines and congenital cataracts--a syndrome? AB - Radiculomegaly of single teeth is very uncommon. Our survey indicates that the canine tooth is most frequently affected. Although illustrated in a number of texts of dental anatomy, there is a lack of detailed case reports. PMID- 2263346 TI - Intranasal teeth: a case report. PMID- 2263347 TI - Monostotic Paget's disease of the mandible. PMID- 2263348 TI - Calcified thyroid cartilage. PMID- 2263349 TI - Bifid mandibular canal. PMID- 2263350 TI - Bilateral calcified stylohyoid ligaments. PMID- 2263351 TI - [Chronic recurrent abdominal pain and lactose malabsorption in childhood]. AB - The Authors examined 515 children with abdominal pain in the outpatient clinics for a period of two years. The pain was frequently periumbilical or mid epigastric with a history of more than two months. Persistent lactose malabsorption was found in 252 children (48,9%), which justifies the use of Breath Hydrogen Test as a first diagnostic procedure for assessing recurrent abdominal pain. Putative pathogens were identified in the stool specimens of 21 patients. Oesophagitis was diagnosed in 18 children and duodenal ulcer in one. 91 patients (less than 6 years old) improved after successful treatment of the chronic upper respiratory inflammations. The authors did not find any causes in 18.1 per cent of the children examined and they think that the abdominal pain in these children may be psychogenic. The use of high-fiber diet is proposed for the later group. PMID- 2263352 TI - [Cardiologic side effects of therapeutic irradiation of breast cancer--early results]. AB - Authors prospectively examined 54 breast-cancer patients treated by postoperative telecobalt (28), or electron therapy (26). They studied the cardiological side effects caused by ionizing radiation. ECG, echocardiography and measurement of the systolic time intervals were performed before, immediately, 6 weeks, 6 months, one and 1.5-2 yrs after the completion of radiotherapy. Twenty-three symptom-free patients were found to have signs of transitorial pericardial irritation, more after telecobalt, than electron therapy (17/6). T-wave inversions were seen on the ECG of twenty patients. In 5 and 3 patients small amounts of pericardial effusion could be detected by echocardiography with, or without ECG alterations, respectively. Other side-effects mentioned by the literature could not be found yet, further follow-up is recommended, however. In the authors' opinion the effect of ionizing radiation, mainly of telecobalt therapy is possibly a risk factor for cardiovascular diseases, it is suggested to be considered at the planning of radiation therapy accordingly. PMID- 2263353 TI - [Wolf-Parkinson-White syndrome in neonatal age]. AB - Description of history data, course of the disease and therapy is given of WPW syndrome diagnosed in neonatal age. In connection with the case the authors deal in details with the etiology, pathomechanism, course and complications of the disease. Problems of differential diagnostics and therapy are discussed. A relatively infrequent case is presented; the importance of pre- and postnatal observation and diagnosis being in close connection with the way of therapy and prognosis is emphasized. PMID- 2263354 TI - [The publication Pax Corporis (Peace of the Body) is 300 years old (Pariz Papai)]. PMID- 2263355 TI - [A forgotten surgeon: Pal Kuzmik]. PMID- 2263356 TI - [Controversies about the sex determination of the fetus]. PMID- 2263357 TI - [Ethical dilemma of gender selection]. PMID- 2263358 TI - [Significance of transvaginal ultrasonic examination in the first pregnancy trimester]. AB - The authors report their results obtained by performing transvaginal sonography in 180 patients in the first trimester of pregnancy. It has been found that both normal and pathological cases could be diagnosed 1 week earlier than had been possible with transabdominal method. Minimum size of the intrauterin gestational sac was found to be 3 mm. Cardiac activity could be evaluated in embrios with a size of 7 mm or greater in all cases. According to them the diagnosis of blighted ovum and missed abortion seems to be confirmed when an "empty sac" is larger than 20 mm, or the absence of heart motion is detected in an embrio greater than 10 mm, without repeated scan. High sensitivity was found in ectopic pregnancies especially in unruptured cases. The possibility of qualitative analysis of "free fluid" in Douglas pouch and diagnosis of congenital anomalies in very early pregnancy are promising. Transvaginal sonography is recommended in all cases when transabdominal technique is equivocal. PMID- 2263359 TI - [Glucose content in blood products]. AB - The glucose content of the main blood products used in Hungary was determined, because the amount of glucose administred together with the blood products may have significance, especially at diabetic patients. The results revealed that there is a substantial difference in the glucose content of the different blood products and the glucose content of the individual products of the same kind may have also substantial difference. The glucose content of cell products depends also on the storage time. Washed red cell products can be ordered in glucose-free form, that is resuspended in glucose-free resuspension medium. Leukocyte concentrate contains hydroxyethyl starch, which will be hydrolysed into glucose in the circulation of the recipient. PMID- 2263360 TI - [Symptoms of spinal osteochondrosis]. AB - Having screened 384 patients suffering from Scheuermann's disease and 2992 eleven year-old children, the authors conclude that the early and salient symptoms of the disease are mobile thoracic kyphosis associated with the flexious contracture of the hip joint, and occasional anteflexious contracture of the shoulder joint together with a left-curved functional scoliosis. The authors analyse the nature and frequency of scoliosis, excluding other causes of the flexion contracture of the hip joint. Their findings are supported by data processed on computer. PMID- 2263361 TI - [Diagnostic and therapeutic experiences with purulent meningitis in adults]. AB - The authors reviewed data of 137 patients with purulent meningitis treated in the period of 10 years. Attention was paid to the frequency of predisposing and associated diseases, to the factors helping and delaying the diagnosis and to those altering the prognosis. The importance of effective supportive care, particulary covering pressure of the CNS as well as specific therapy was stressed. The circumstances and the conditions of management depending on the condition of the patient was emphasized. Thirty eight of patients (27%) has died. PMID- 2263362 TI - [Relationship between salt intake and urinary electrolyte elimination over a 24 hour period in children]. AB - This study was undertaken to estimate daily salt intake by measuring urinary electrolyte excretion in 203 healthy children with age of 0-17 years. Daily sodium excretion increased steadily with advancing age from 7.56 +/- 4.02 (mean +/- S.E.) (mmol/die) in infancy to 43.7 +/- 22.6 at 1-3 years, and to 164.70 +/- 74.70 at 15-17 years respectively. The corresponding values of daily potassium excretion were 13.93 +/- 6.30, 7.12 +/- 4.70 and 30.90 +/- 31.20 mmol/die at the respective ages. When expressed per kg body weight sodium excretion proved to be the highest at 5-7 years of age, while the maximum of potassium excretion was seen during infancy. As a result, the sodium to potassium ratio increased significantly from 0.62 during infancy to 6.50 at age of 1-3 years without consistent change later on. No significant difference could be detected in electrolyte excretion between the groups with normo-or hypertension. The marked elevation of daily sodium excretion and sodium to potassium ratio occurring after one year of age may be accounted for by the introduction of adult type feeding pattern. PMID- 2263363 TI - [Bouveret syndrome diagnosed by endoscopy]. AB - The case of a 74 years old woman suffered from a gallstone disease for 5 years is reported. In the background of the upper abdominal pain and vomiting, which necessitated her hospitalization, a large-size gallstone penetrated into the duodenal bulb and obstructed pyloric channel was found by endoscopic examination. The upper duodenal ileus was verified during the operation, gastroduodenotomy and cholecystectomy were performed, and the 7 x 4 cm size gallstone was removed. After a complications free period the asymptomatic patient went home. Our above reported case is a preoperatively, endoscopically diagnozed Bouveret's syndrome. PMID- 2263364 TI - Differences in the legibility of letters at contrast threshold using the Pelli Robson chart. AB - One disadvantage of using high-contrast letters as test objects when measuring visual acuity is the fact that they are not of equal legibility. A number of charts are now commercially available that assess contrast sensitivity using letter targets. This study attempted to assess the legibility of letters at contrast threshold on the Pelli-Robson letter contrast sensitivity chart by determining the percentage of correct responses for each of the ten Sloan letters at contrast threshold. Results of 493 contrast sensitivity measurements taken in optometric practice indicated that there is a definite difference in legibility between letters at contrast threshold as for letters at acuity threshold. The data suggest that the probability of correctly identifying two out of a group of three letters at threshold on the Pelli-Robson chart varies between 67% and 97% due to letter type alone. Because of the very regular and pronounced miscalling of the letter C as an O, we suggest that this should be accepted as a correct call during threshold measurements on the Pelli-Robson chart. This helps to balance the legibility of different groups of letters. PMID- 2263365 TI - Visual fitness to drive after stroke or head injury. AB - The visual requirements for driving in Britain are outlined and how they might be compromised following stroke or head injury examined. The role of the optometrist in assessing such patients who wish to resume driving is discussed. Topics discussed include legal considerations, the relationship between visual problems and driving ability and the vision-testing techniques that are most appropriate for use with the brain injured. An illustrative case history is presented. PMID- 2263366 TI - Ocular hazards arising from depletion of the natural atmospheric ozone layer: a review. AB - The processes contributing to the maintenance of the natural, atmospheric, ozone layer, which screens the earth's surface from solar ultraviolet radiation at wavelengths below 300 nm, are described. The possible adverse effects of man-made chemicals such as chlorofluorocarbons (CFCs) on this layer are outlined. Consideration of the flux of ultraviolet light reaching the earth's surface as a function of the ozone concentration and other factors allows the effect of ozone changes on ocular health to be evaluated. It is concluded that the changes of the order of a few per cent that are predicted by current models of the atmosphere, and which are comparable with natural fluctuations in ozone, would have relatively little effect on the incidence of solar keratitis at the cornea. Larger changes, in the order of 50%, would be expected to have a significant effect. There might also be an increase in the incidence of brunescent cataract. Ozone changes would have a negligible effect on the amounts of solar radiation reaching the retina. PMID- 2263367 TI - Corneal desiccation staining with hydrogel lenses: tear film and contact lens factors. AB - This investigation monitored the response of established contact lens wearers using contact lenses made from Filcon 4a 77% water-content material in three different thicknesses (0.08, 0.10 and 0.12 mm) over a 6-hour period of wear under adverse environmental conditions. The results obtained showed the following. (1) In accordance with previous studies carried out with lenses of similar water content, the present lenses produced corneal desiccation staining under the challenging conditions of use. However, the staining produced was similar for all three lens thicknesses tested. (2) Corneal desiccation staining was present despite the good and stable fitting characteristics observed during the study, confirming that mechanical trauma is not a necessary cause for soft-lens-induced desiccation staining. (3) Corneal desiccation staining was associated with a rapidly destabilizing pre-lens tear film (PLTF) and a thinning lipid layer. The initial break-up of the PLTF and corneal staining were recorded with a higher incidence in the vertical quadrants than in the horizontal quadrants. The PLTF is thinnest and most unstable at the tear prism margin border, hence least efficacious at preventing evaporation. Corneal desiccation staining may be due, at least partly, to excessive evaporation at the contact lens front surface. PMID- 2263368 TI - The Edridge-Green lecture vision at low light levels: role of spatial, temporal and contrast filters. AB - One of the most impressive features of our vision is the fact that we see with good sensitivity over such a large range of light levels. This process is usually termed light adaptation by which it is meant that the sensitivity of individual neurones within the retina automatically adapts to suit the prevailing lighting conditions. Although this is usually thought about in terms of single neurones, its effectiveness is greatly enhanced by the fact that individual neurones have distinctive properties. The fact that individual neurones can be considered as acting as neural filters along the dimensions of size, time, orientation and contrast means that visual information is distributed across the whole neuronal population which in turn plays an important role in extending our dynamic range. In this paper the distributed nature of visual processing is emphasized and its role in extending the range of light levels over which we can see is highlighted. PMID- 2263369 TI - Joint hypermobility in keratoconus. AB - There are several reports linking keratoconus and connective tissue disorders, such as Ehlers-Danlos syndrome, osteogenesis imperfecta and mitral valve prolapse, suggesting that keratoconus may be the result of a localized dysfunction in collagen metabolism. In view of this the incidence of hypermobility of the joints among a group of patients with keratoconus was compared with a normal (matched) control group. Eighty-four patients were examined using the Beighton modification of the Carter and Wilkinson scoring system. A control group matched for sex, age and ethnic group was also assessed. No statistically significant difference between the groups was found for the trunk or knees; a difference was found for the metacarpo-phalyngeal and wrist joints. The findings support the theory that keratoconus is a localized manifestation of a mild connective tissue disorder. Also, it can be stated that patients with keratoconus are five times more likely to show hypermobility of the metacarpo-phalyngeal and wrist joints. PMID- 2263370 TI - Statistical inference on mean dioptric power: hypothesis testing and confidence regions. AB - It has not hitherto been possible to apply formal methods of statistical analysis to data on dioptric powers. The solution to the basic statistical problem is now provided in this paper. Recognition of the matric-variate nature of dioptric power allows calculation of sample means and variance-covariances. These in turn can be used to calculate a statistic for testing hypotheses on population means and for obtaining confidence regions for those means. In a graphical representation of dioptric power the confidence region turns out to be an ellipsoid centred on the mean of the sample of dioptric powers. The theory is illustrated by means of numerical examples. Singularity of the variance covariance matrix may occur especially when the sample is small. When it does occur it is the cause of some difficulty in applying the statistics. Nevertheless singularity is rare in practical situations and can usually be avoided simply by increasing the size of the sample. Singularity, therefore, is not treated fully in this paper. Dioptric power is essentially four-dimensional in character but in practice a three-dimensional subspace is almost always sufficient. To avoid the difficulty of having to represent four-dimensional shapes and to avoid the complication of singularity (which is the rule rather than the exception in practice in four-space) only the common three-dimensional problem is considered in detail. PMID- 2263371 TI - An extension of Helmholtz's explanation of Listing's law. AB - Helmoholtz argued that the eye moves in accordance with Listing's law to ensure that objects have the same apparent direction despite changes in the point of fixation. Listing's law ensures that the same pattern of image displacements is associated with a given eye movement, independent of the initial point of fixation. His explanation has been extended to the problem of ensuring that objects remain at the same apparent depth, with both direct and indirect fixation. This problem is simplified if disparity is analysed in the region of the frontal plane. PMID- 2263372 TI - Essay on the physiology of reading. PMID- 2263373 TI - Measurement of the posterior corneal radius using slit lamp and Purkinje image techniques. AB - A method for measuring the radius of the posterior corneal surface using the first and second Purkinje images has recently been developed. Values for the posterior corneal radius in the vertical meridian obtained using this method are compared with those obtained using a more conventional slit lamp method. A good correlation was found between values obtained using the two methods. PMID- 2263374 TI - Geometrical ray-tracing: a 'ray free' method. AB - A new geometrical method of determining the location of the image of an optical component is described. This method does not require rays to be drawn. It can be applied to refractive and reflective components as well as multi-component systems. PMID- 2263376 TI - Light scatter in cataractous lenses. PMID- 2263375 TI - Concurrent visual conversion reaction and simulated colour vision defects in a 12 year-old child. AB - Visual conversion reaction (VCR) is a psychosomatic anomaly which occasionally manifests in children, most commonly in the form of reduced vision and visual field defects. Malingering or conscious simulation for secondary gain would appear to be rare in children but occasionally VCR and simulation coexist. A case history is presented of a 12-year-old child with behavioural and reading difficulties who manifested reduced vision most probably attributable to VCR and severe colour deficiency, which was best explained in terms of simulation or malingering. PMID- 2263377 TI - Prismatic effects of spherical and astigmatic lenses: Imbert's pioneer analysis of 1886. PMID- 2263378 TI - The sine-squared expression and torsional prismatic effects in astigmatic lenses. PMID- 2263379 TI - Accommodative convergence and age. PMID- 2263380 TI - Axial chromatic aberration: linear or power function of wavenumber? PMID- 2263381 TI - [Epidemiologic and tonometric results of a multicenter study of 5,872 patients with ocular hypertension or open-angle glaucoma treated with betaxolol]. AB - A large french multicenter study has been conducted by 750 ophthalmologists with 5,872 patients with open angle chronic glaucoma or intraocular hypertension. The patients were treated twice a day for a period of six months with Betaxolol eye drops, a Beta-1 betablocker product, and cardioselective. Concerning the total population of patients, 35% had a cardiovascular systemic context, 12.1% had a pulmonary systemic context, 5.2% were diabetic patients. Efficacy, systemic tolerance, visual comfort have been evaluated during the study, for each group of patient. After six months of treatment, intra-ocular pressure of the 5,872 patients has been lowered from 22.61 mmHg to 18.25 mmHg. Patients have reported a global efficacy in 97% of cases, a good systemic tolerance in 91% of the cases. The investigations have reported a global efficacy in 96% of cases and a good systemic tolerance in 91%. Ocular comfort has been reported as acceptable by 89% patients and by 92% of the Investigators. The analysis of the results of the study allows us to say that the Beta-blocker-Beta-1 selective eye drop, can be used in treatment of intraocular hypertension or open angle chronic glaucoma with a high range of efficacy and safety. PMID- 2263382 TI - [Analytic study of electroretinograms of 280 patients treated with synthetic antimalarials]. AB - An analytic study of electroretinogramms (ERG) from 280 patients under antimalarial therapy has been made. The pratician has stopped treatment in 4.8% of the ERG. Among the investigated parameters, the only statistic difference is the cumulative doses. PMID- 2263383 TI - [Therapeutic considerations in retinal detachments caused by macular hole]. AB - The authors analyse 24 observations of retinal detachment with macular hole in high myopia. All this patients have been treated by C3F8 internal tamponade. Silicon oil has been only used for recurrences. After a study of vitreoretinal connections, the cause of recurrences are analysed according to echometry, detachment degree and proliferative vitreoretinopathy. PMID- 2263384 TI - [Elimination of viscoelastic substances from the vitreous cavity. Comparative study of sodium hyaluronate and hydroxypropylmethylcellulose]. AB - We study the elimination of two viscoelastic substances from the vitreous cavity: the Hydroxypropyl Methylcellulose and the Sodium Hyaluronate that are potentially vitreous substitutes. We performed gas-vitrectomy in 116 eyes of 58 rabbits. Three days after surgery we performed gas-viscoelastic substance exchange. We analyzed the concentration of Hydroxypropyl Methylcellulose and Sodium Hyaluronate with diphenylamine reaction at different periods: zero, 1 week, 2 weeks, 1 month till 6 months. In both cases the elimination is fast so that 1 week after the intravitreal injection remains only 60.1% of the Hydroxypropyl Methylcellulose and 100% of Sodium Hyaluronate, and two weeks after 38.5% of Hydroxypropyl Methylcellulose and 62.5% of Sodium Hyaluronate. We conclude that both substances have a short half life-time specially in the case of the Hydroxypropyl Methylcellulose. PMID- 2263385 TI - [Biocompatibility of hydroxypropylmethylcellulose as a vitreous substitute in rabbits]. AB - We have studied the biocompatibility of the hydroxypropylmethylcellulose in ten rabbits' eyes after lensectomy and posterior vitrectomy. In seven eyes the inflammatory reaction was severe. The reason why the hydroxypropylmethylcellulose is biocompatible in the anterior segment and not in the vitreous body seems to be explained by its quantity and its concentration in the eye at the end of the surgical procedure. PMID- 2263386 TI - [Intolerance to encircling. 19 cases of section or ablation of encircling]. AB - Removal of ten encircling scleral buckles and section with relaxation of nine encircling buckles are displayed. Only episcleral buckles with oval or round silicone sponge exoplants are analyzed. Besides infection (three eyes), removal or section was required because of too tight encircling elements (16 eyes). Anterior buckles created by invagination of encircling elements, without horizontal shortening avoids this risk of constriction. PMID- 2263387 TI - [Current limitations of radial keratotomy]. AB - The so-called R.K. classic technique gives good results for myopias under 5 diopters. We have performed different modifications of the technique for the 8 incisions--optical zone 3 mm R.K. 8 incisions--O.Z. 3 mm. Downhill incision direction or "American technique" incisions (from the O.Z. towards the limbus). 8 incisions--O.Z. 3 mm + a deepening of 20 microns from a 6 mm O.Z. Repeat operations (Stan Franks Backcutting technique or addition of incisions). 8 incisions--O.Z. 3 mm. Uphill incision direction or "Russian technique" (from the limbus towards the optical zone). This study was carried out with 134 R.K. and shows that we get best results for myopias between 5 to 7 diopters, with the last technique (Uphill incision direction). PMID- 2263389 TI - [Superior oblique paralysis]. AB - The physiopathological features concerning the affected and the fellow eye were considered. As far as the diagnosis is concerned, the test of Bicas, examination of binocular rotations and of versions, and the Maddox double rod test are discussed; the features of a bilateral palsy were stressed. For surgical treatment, the various weakening procedures of the inferior oblique are evaluated. The author's technique for resection of the superior oblique is described. PMID- 2263388 TI - [A monocanalicular stent with self-stabilizing meatic fixation in surgery of excretory lacrimal ducts. Initial results]. AB - Our experience of 49 cases with a new monocanalicular silicone stent is described. This is a stent with a "auto-stable" meatic plug which respects the canalicular anatomy. There is no stopping-knot, no palpebral ring as in the bicanaliculo-nasal-intubation. The risk of accidental exteriorization is less important, the risk of stricturotomy is absent. Two types of intubation can be used: monocanaliculo-nasal intubation: the way of putting it in place is the same as the bicanaliculo-nasal one, with a metallic probe. The range of it's use widdens from distal canalicular wounds (2 cases) to common canalicular stenosis (15 cases) and to lacrimo-nasal imperforations (12 cases). In the two last instances, the intubation is made through the superior canaliculus, so that the inferior one is left free. In 13 cases, an intubation was made bilaterally for the same disorder, and a comparison could be done between monocanalicular and bicanalicular intubation. The true monocanalicular intubation, for proximal injuries: grasping the metallic probe inside the nose is no longer necessary. The length of the silicone probe is adaptated intra-operatively. The functional results of monocanalicular intubation are comparable to the results of bicanalicular intubation, especially for monocanalicular injuries (in addition with canalicular sutures) and the lacrimo-nasal imperforation. Incidents were observed especially with the first patients; a strict method is mandatory for avoiding accidents. The use of monocanalicular intubation should be used only for short duration and monocanalicular disorders. In other cases, bicanalicular intubation remains the good choice. PMID- 2263390 TI - [Brown's syndrome]. AB - Having observed a very tight adhesion between the trochlea and the tendon of the obliquus superior bulbi muscle or an increase in tendon thickness posterior to the trochlea in operated patients, the author tried to correct this abnormality using partial trochleotomy and the lysis of the adhesions, followed by the application of Scott-Knapp sutures. The morphological basis of Brown's syndrome, consisting of an obstruction at the level of the trochlea, was demonstrated experimentally by means of an eye motion simulator. PMID- 2263391 TI - [Individualization of X-flavimaculated macular dystrophy in hereditary macular dystrophies]. AB - X-shaped macular dystrophy with flavimaculatus flecks is individualized of other heredo-macular dystrophies. This aspect was showed in two families with a retinal pigment epithelial dystrophy characterised by an X-shaped yellowish macular lesion and numerus flavimaculatus retinal flecks. Nine members were variously affected. The condition was bilateral, had a dominant inheritance, started in middle age with a slow-developing macular lesion. Visual functions were often minimally disturbed for two or three decades. Relations with others here domacular dystrophy are discussed particularly with pattern dystrophy. PMID- 2263392 TI - [Ocular cysticercosis, typical forms and treatment]. AB - We report two personal cases of intra ocular cysticercosis typical by their sub retinal and intra vitreous localization. After a short review of epidemiology and biological diagnostic we propose a treatment which associates a medical part with Praziquantel, killing the larva and a surgical part with pars plana vitrectomy allowing the control of the inflammation, contemporary of the larva's death and the intra-vitreous cysticercosis extraction. PMID- 2263393 TI - [Human alfa-2b in rabbit's eyes]. AB - The toxicity of human interferon alpha 2b in rabbit's vitreous and conjonctiva is studied through electroretinography, echography, angiography and histological examination. Interferon was injected in increasing doses 150,000 UI, 500,000 UI and 1,000,000 UI. The results from examinations in the rabbits are presented and the conclusion is drawn, that good tolerance is achieved, even at higher doses. PMID- 2263394 TI - [Influence of light through the eyes on metabolism and hormones]. AB - The eye plays a double role: on the one side it is the optic camera, on the other side independent of the optic path ways it is the light receptor which stimulates the retino-hypothalamique pathway of the endocrine-visceral system. To determine this influence, we compared the metabolisme (water balance, blood sugar and blood cell count) as well as the hormones (ACTH, Cortisol) of fifty patients with bilateral almost total cataract, before (practically blind) and after cataract surgery (regain of light). There was a significant difference between the metabolic and hormonal values before and after cataract extraction, reaching physiologically normal levels due to the stimulating influence of light after the operation. PMID- 2263395 TI - Comparison of growth hormone-releasing effect of growth hormone-releasing hormone, clonidine and pyridostigmine in normal children and adolescents. GH releasing effect of GHRH, clonidine and pyridostigmine. AB - The GHRH test has been proposed to replace conventional stimuli in the diagnosis of GH deficiency. However the reliability of GHRH in discriminating between normal and GH-deficient children is still uncertain. The aim of this study was to compare the GH-releasing effect of GHRH (1 microgram/kg i.v.) with that of two neuroactive drugs, clonidine (CLON, 150 micrograms/m2 orally), an alpha 2 receptor agonist, and pyridostigmine (PD, 60 mg orally), a cholinergic agonist that inhibits cholinesterases, in 23 children and adolescents with normal and familial short stature. The plasma GH peak (mean +/- SEM) after GHRH (20.3 +/- 2.5 ng/ml), CLON (17.0 +/- 2.1 ng/ml) and PD (14.9 +/- 1.5 ng/ml) did not significantly differ. According to the conventional limit (less than 10 ng/ml), a false negative response was present in 6, 5 and 6 subjects after GHRH, CLON and PD, respectively. In conclusion, GHRH, CLON and PD have a similar GH-releasing effect. A similar percentage of false negative responses was observed with all tests and this evidence reduces their diagnostic ability. PMID- 2263396 TI - The bioelectronic connectional system (BCS): a therapeutic target for non ionizing radiation. AB - Among cells and extracellular matrix have been demonstrated reciprocal interactions of oriented morphogenesis. As collagen fibers of the matrix, keratin filaments of desmosomes and the cytoskeleton elements are all piezoelectric substances, with particular biophysical characters, it is possible that these three classes of biostructures are the morphological expressions of a large and unitary cooperative system for coherent communication among cells, by means of piezoelectric interactions and photon/phonon transduction of electromagnetic signals, both endogenous and exogenous. The Author has proposed in 1989 to classify this morphofunctional complex as a bioelectronic connectional system (BCS), in which connective tissue is largely included, but the functions of which go well beyond its classical mechanical ones. The hypothesis is consistent both with the model of Welch and Berry (protonic energy continuum) and with the concept of bioplasma (Inyushin, Sedlak et al.). Physiology and pathology of BCS could also work as a starting point for experimental research aiming at inducing order in biostructures by means of non ionizing radiation. PMID- 2263397 TI - Screening a family for hereditary chronic pancreatitis. AB - Chronic "idiopathic" pancreatitis (CP) in a 7 year-old-boy, whose father has suffered from CP, and whose former grandfather had suffered from pains possibly of pancreatic origin, led us suspect a hereditary etiology. An analysis, extended in a control fashion to the relatives of the healthy spouse of the affected grandfather, surprisingly revealed 2 more proven and 3 more suspected CP, giving the overall number of 8 affected members in this 35-member 3 generation kindred and revealed a maternal heredity instead of paternal heredity (which was first thought to be apparent). We therefore recommend that in a family suspected to suffer from hereditary CP (HCP), a screening should be extended to cover even the unaffected spouse's family--the present extended study revealed for 23 new members them to belong in an affected family. Without an extensive screening advises for family planning, alcohol consumption etc. can not be given. Plain abdominal X-ray accompanied with epigastric ultrasonographic are suitable for screening, which might be extended to every individual in smaller families, but may be safely restricted to the members ever suffered from epigastric pains in the case of a huge family. Pancreatic duct anomalies, hyperlipidaemia, hypercalcaemia, aminoaciduria or hyperimmunoglobulinaemia, all of which have been seen to accompany HCP, were not present in this family. Neither was any linkage found between the penetrance of HCP and ABO/Rh blood groups or HLA haplotypes. PMID- 2263398 TI - Respiratory function during oxygen administration in chronic obstructive pulmonary disease. AB - Patient with severe chronic obstructive pulmonary disease (COPD) can develop respiratory muscle weakness and fatigue. Arterial hypoxemia can predispose to this condition. To assess whether O2 administration improved respiratory muscle function and respiratory pattern in COPD 11 patients with chronic hypoxemia were examined. Each patient was first submitted to respiratory function studies, including lung volumes, in normal and recumbent position, respiratory frequency, Ti/Te, Ti/Tot, maximal inspiratory and expiratory pressures (Pimax, Pemax) and arterial gas analysis breathing room air. All these tests were repeated during oxygen Administration through a nasal cannula. The arterial PO2 improved from 50 +/- 7 mmHg to 81 +/- 28 mmHg but the breathing pattern, Pimax and Pemax as well as lung volumes remained unchanged. It is concluded that oxygen, in short term administration, doesn't influence respiratory pattern and muscle function. PMID- 2263399 TI - Traumatic pathology of the thoracic aorta. Personal experience based on 42 cases. AB - Between 1974 and 1989, 42 patients have been operated on at the Istituto di Chirurgia Generale e Cardiovascolare of University of Milan, for traumatic pathology of the thoracic aorta: in 14 cases it occurred an acute rupture at the level of aortic isthmus and in 28 cases a posttraumatic fals aneurysm. We had an operative mortality of 28% (4 cases) in the acute rupture: 3 patients died for neurological complications which were present at hospitalization. In one case appeared a serious ARDS. We had no surgical deaths in patients operated on for the posttraumatic false aneurysm. In 15 cases, the patients suffered for a postoperative paraplegia. Surgical indications are discussed, overall for the posttraumatic false aneurysms. The authors consider the advantage and the risks of the use of ECC and of total heparinization of the patients. PMID- 2263400 TI - Long-term relapses in breast cancer patients. AB - The authors examined 100 cases of long-term relapses of breast cancer arising more than 5 years after radical mastectomy and 100 cases of early relapses (within 3 years). Precautional radiotherapy or chemotherapy had not been performed during these intervals. Histologic type did not appear important. Long term relapses were relatively less frequent than early relapses at the level of the locoregional lymph nodes (P less than 0.01). Other investigations were directed to the eventual importance of hormones on the incidence of long-term relapses. Since many of the cases were not recent and therefore no data were available as regards hormone receptors, it was impossible to base the study on the latter. The incidence of long-term relapses was considerably lower in postmenopausal than in premenopausal patients and lower than the incidence observed for early relapses (P less than 0.04). This finding could be attributed to a hormonal effect. Therapeutic oophorectomy determines relatively better results in cases with long-term relapses, but their survival does not appear to be significantly better than that of cases with early relapses. Among the patients with long-term relapses, the N - cases at the time of mastectomy were relatively more numerous than observed among cases with early relapses (P less than 0.04). This finding, which also explains the relatively minor frequency of long-term relapses in locoregional lymph nodes, reduces the prognostic importance of the histologic status of axillary lymph nodes, as is well known for patients with hormonal receptors. PMID- 2263401 TI - Role of Ca++ antagonists (nifedipine) in the long-term prognosis of hypertensive patients with previous history of myocardial infarction. AB - One hundred and twenty-two patients suffering from slight or moderate essential arterial hypertension with a previous history of myocardial infarction were selected for inclusion in this study. Patients were divided into two groups of 61 according to the type of anti-hypertensive therapy received. Patients in Group 1 received nifedipine (30 mg p.d.), while patients in Group 2 were treated using other anti-hypertensive therapy (diuretics, alpha-methyldopa, clonidine, indapamide). At the end of the follow-up period, which lasted 5 years, a statistically significant improvement in the following factors was observed in Group 1 in comparison to the control group: (a) an improved response of both SBP (p less than 0.001) and DBP (p less than 0.001) levels to anti-hypertensive therapy; (b) a more significant diminution in the thickness of the interventricular septum (p less than 0.001) and the posterior wall of the left ventricle (p less than 0.001) assessed using ultrasonography; (c) a reduced number of cases of post-infarction angina (p less than 0.05); (d) fewer cases of recurrent infarction (p less than 0.05); (e) fewer deaths as a result of re infarction (p less than 0.01). These results confirm that the vascular and cardioprotective effects of nifedipine give a good long-term outcome in hypertensive patients with a previous history of myocardial infarction. PMID- 2263402 TI - A hydrogen-harps model for intracellular communication and its implications for the second genetic code. AB - Hydrogen bonds (HB) in proteins and nucleic acids oscillate with frequencies of 10(11)-10(12) Hz, so giving rise to mm waves and far infrared emission. As HB undergo stretching and compression, their oscillation frequency will correspondingly change. The author (1989) 1b has devised a "musical" model, in which HB are compared to the strings of a string instrument: the harp. On the length, number and cooperation of "strings" (small and large hydrogen-harps) will depend the frequency, intensity and quality of "sound" (i.e. electromagnetic emission). Of course, this elementary hydrogen-harps model needs a physico mathematical development. Nevertheless it can already be utilized to explain some essential moments of proteins and DNA function, on the base of its logical connection with Frohlich's theory of coherent excitations. It might also help the understanding of the second genetic code mechanisms. PMID- 2263403 TI - Long-term follow-up of patients with sacral anterior root stimulator implants. AB - The first 50 patients to receive a sacral anterior root stimulator for bladder control were reviewed by questionnaire in mid-1989. At that time, the follow-up period varied from 5 to 11 years, and 48 of the group were alive; 2 had died from unrelated causes. Forty-one used their implants regularly for micturition and of these, 37 were always or usually continent. Twenty-nine reported no symptomatic urinary infections in the previous year, and only 4 had 3 infections or more. Twenty-seven used their implant to assist defaecation, and 13 of 32 male users reported full implant-driven erections. Side effects are minor, except for stimulus evoked pain sensation, which prevents use of the implant in 3 of the 7 non-users. Two of the other non-users were awaiting repair of their implant faults. PMID- 2263404 TI - The quality of life of three functional spinal cord injury subgroups in a Swedish community. AB - Vast community provisions in Sweden are intended to offer spinal cord injury (SCI) subjects equal opportunities and the same living standards as the able bodied. This study on all 56 subjects representing 3 distinct functional subgroups, out of a consecutive series treated at a Spinal Unit, explored the skills used in a wide range of community living activities and the details of these subjects' quality of life (QL). C6-tetraplegics with complete lesions (n = 15), wheelchair-bound paraplegics (n = 23) and ambulant paraplegics (n = 18) varied in physical independence in proportion to their disabilities but disturbances of mood states and QL perception did not differ between groups or from a control population sample. Eighty per cent of the subjects were engaged in gainful employment or education. Work/education, home management and mobility in the neighbourhood were clearly restricted by more severe disability but social and recreational activities were not. Degree of social activity and ability to drive a car were closely associated with levels of mental well-being and of perceived QL. Access to transport and home-help services, appropriate housing and technical aids included few unmet subjective needs, possibly explaining why these environmental factors did not inhibit the activity levels of the study population. Extensive society support and stimulation can satisfy important needs and expectations of well-functioning SCI subjects. PMID- 2263405 TI - The portrayal of paralysis in some masterpieces by European painters. PMID- 2263406 TI - Citrate excretion in spinal cord patients. AB - Low urinary citrate is a risk factor in calcium renal stone disease. The aim of this work was to identify the factors responsible for the low excretion of citrate frequently observed in patients with spinal cord lesions. Thirty male patients with spinal cord lesions were studied by blood and urine biochemistry. The most important single factor related to urinary citrate was urinary potassium. The presence or absence of urinary stone disease and variations in urinary volume also contributed significantly to variations in citrate excretion. Determination of plasma and urinary citrate, urinary sodium and bacteriological culture of urine permitted complete discrimination of the 7 stone formers from the other patients. PMID- 2263407 TI - Estimating the user population of a simple electrical stimulation system for standing. AB - Many laboratory demonstrations have been reported on standing or walking with the aid of electrical stimulation. These demonstrations have typically been in small numbers of selected spinal cord injured individuals. The extent to which this technology might ultimately be applicable to the spinal cord injured population at large is not presently known. This study reports estimates of the size of the potential user population of a specific surface electrical stimulation device and protocol. The medical records were reviewed of 192 patients with traumatic thoracic, lumbar, or sacral spinal cord injury resulting in paraplegia. Based on the inclusionary criteria, between 20 and 48 patients (10.4% and 25%) of this sample population could be considered eligible for this surface stimulation protocol. As approximately 45% of the USA population of spinal cord injured individuals have paraplegia, the results suggest that between 4.7% and 11.25% of all spinal cord injured persons in the USA might be potential users of this particular electrical stimulation technology. PMID- 2263408 TI - Exercise capacity of untrained spinal cord injured individuals and the relationship of peak oxygen uptake to level of injury. AB - Twenty spinal cord injured individuals were tested for maximal oxygen uptake (VO2 peak using a hysteresis brake wheelchair ergometer. The subjects were divided into 4 groups as follows: (a) quadriplegics (4 subjects); (b) untrained female paraplegics (5 subjects); (c) untrained male paraplegics (7 subjects); and (d) trained male paraplegics (4 subjects). The VO2 peak were analysed by a one way ANOVA and Fisher's LSD multiple comparisons. The F-ratio (50.93) was significant (p = less than 0.0001). Fisher's LSD post hoc multiple comparisons found the following differences: (a) quadriplegics were significantly lower than the untrained paraplegic females, untrained paraplegic males and trained paraplegic males; (b) untrained females were significantly lower than the untrained male paraplegics, and trained paraplegic males; (c) untrained paraplegic males were significantly lower than the trained male paraplegics. A Spearman Rho correlation was calculated using injury level and VO2 max for all the untrained SCI individuals. The correlation was 0.68 and had a significance level of 0.0019. The present study combined with the known research literature gives strong evidence that VO2 peak in the untrained SCI is highly related to level of injury. PMID- 2263409 TI - Neurological improvement following respiratory support in syringomyelia: case report. AB - Respiratory failure in syringomyelia has rarely been reported. We report a patient with syringomyelia who showed some neurological improvement after intermittent respiratory support with negative and positive pressure ventilation. PMID- 2263410 TI - Eimeria species which infect the chicken contain virus-like RNA molecules. AB - There is increasing support for the presence of viruses and virus-like particles inside protozoan cells. This study describes viral-like RNA molecules that have been detected in two species of Eimeria that infect the chicken. The RNA molecule identified in E. maxima has been characterized: subcellular fractionation studies have shown that the RNA is present in the cytoplasm, probably as an abundant ribonucleoprotein that is insensitive to RNAse A treatment. Electron microscopy has demonstrated that this RNA molecule is double stranded. In addition, all E. maxima strains examined so far contain this RNA molecule. PMID- 2263411 TI - Characterization of Trichomonas vaginalis haemolysis. AB - The haemolytic activity of live Trichomonas vaginalis organisms was investigated. Optimal haemolysis of human erythrocytes was observed at a parasite to erythrocyte ratio of 1:5 during a 2 h incubation period. No haemolytic activity was detected in concentrated culture supernatants after overnight growth of trichomonads or when parasites were separated from erythrocytes by a 3 microns filter, suggesting a contact-dependent mechanism for haemolysis. The haemolytic activity was temperature-dependent and maximal haemolysis occurred at 37 degrees C. Treatment of trichomonads with metronidazole reduced levels of haemolysis by greater than 50%. Maximal haemolysis occurred at the pH range of the vagina during trichomoniasis. N-alpha-tosyl-L-lysyl-chloromethyl ketone and iodoacetamide, inhibitors of trichomonad cysteine proteinases, reduced the haemolytic activity of live parasites. PMID- 2263412 TI - Monoclonal IgM rheumatoid factor-like anti-globulins enhance the inhibitory effects of Plasmodium falciparum-specific monoclonal antibodies in vitro. AB - Monoclonal IgM rheumatoid factor-like anti-globulins were produced by in vitro stimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites of Plasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas. In vitro, these anti-globulins augmented the inhibitory effects of P. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases. PMID- 2263413 TI - A rhoptry antigen of Plasmodium falciparum is protective in Saimiri monkeys. AB - A non-polymorphic antigen associated with the rhoptry organelles of Plasmodium falciparum has been purified by immunoaffinity chromatography. The antigen, RAP-1 (rhoptry associated protein-1), which is defined by monoclonal antibodies which inhibit parasite growth in vitro, is a multi-component antigen consisting of four major proteins of 80, 65, 42 and 40 kDa and two minor proteins of 77 and 70 kDa. These proteins were electro-eluted from preparative sodium dodecyl sulphate polyacrylamide gels and protected Saimiri sciureus monkeys from a lethal blood stage infection of P. falciparum malaria. Sera from the protected animals recognized only proteins of the RAP-1 antigen when used to probe a Western blot of total parasite protein extract, confirming that RAP-1 is responsible for eliciting the protective immune response. PMID- 2263414 TI - Bloodmeal digestion by strains of Anopheles stephensi liston (Diptera: Culicidae) of differing susceptibility to Plasmodium falciparum. AB - Blood digestion was studied in strains of Anopheles stephensi which had been genetically selected for either refractoriness or susceptibility to infection by Plasmodium falciparum. Females of the refractory Pb3-9a strain ingested more blood than selected (Sda-500) and unselected (Punjab) susceptible females and began to degrade the haemoglobin soon after feeding. In susceptible females, haemoglobin degradation started only after a significant post-feeding lag period. Total protein content of the midgut after the bloodmeal was correspondingly higher for refractory than for susceptible females, but absolute and relative rates of protein degradation were not significantly different between the different mosquito strains. Bloodmeal induction of midgut trypsin activity and the maximal trypsin activity were the same for the different strains. The residual aminopeptidase activity and its relative post-feeding activity (enzyme units per midgut) were significantly higher in refractory females. However, when converting to specific aminopeptidase activity, no differences between strains were evident. The results indicate that both the early initiation of haemoglobin degradation and higher aminopeptidase activity in the Pb3-9a refractory strain are important in the limitation of parasite development within the mosquito midgut, whereas trypsin plays no role in this process. PMID- 2263415 TI - Praziquantel treatment of Biomphalaria glabrata infected with Schistosoma mansoni -influence on snail fecundity. AB - Praziquantel, administered over a 72 h period in the food of mature Biomphalaria glabrata harbouring 7-week-old Schistosoma mansoni infections, dramatically reduced the numbers of cercariae shed. Doses of 20-30 micrograms/g body weight (including shell weight) reduced shedding by 85-95% over 5 weeks before recovery was evident. Suppression of cercarial shedding in these infections was accompanied by the temporary recovery of the snail reproductive regression due to S. mansoni infection. Snail fecundity was subsequently re-suppressed 2 weeks prior to recovery of the parasite as evidenced by a resumption of cercarial shedding. Praziquantel destroyed mature and developing cercariae within the daughter sporocysts but had no apparent effect on daughter sporocysts; this may account for the eventual resumption of cercarial production. Reproductive failure of the snail is apparently related to the latter stages of cercarial development specifically. Reproductive recovery did not occur when snails were infected as juveniles or when mature-infected snails harboured 12.5 week i.e. older infections: drug treatment temporarily inhibited cercarial production but no snails produced eggs. PMID- 2263416 TI - Studies on intrategumental pH and its regulation in adult male Schistosoma mansoni. AB - The intrategumental pH in adult male Schistosoma mansoni as measured with pH sensitive microelectrodes is between 7.0 and 7.2, a value about one pH unit more alkaline than expected for equilibrium. This value is maintained for at least 4 h after isolation in media buffered with Hepes or CO2/HCO3- with or without serum present. CCCP (1 microM) and FCCP (10 microM) cause rapid acidification. DNP (1 mM) and Na-orthovanadate (1 mM) acidify but also cause significant depolarization of the tegument. NH4+ (20 mM) depolarizes and acidifies the tegument with no evidence of transient alkalinization. High K+ (25 mM) accelerates the acidification. Removal of the NH4+ causes a large transient further acidification with recovery requiring as long as 40 min. High K+ (25 mM) delays the early stage of the recovery. Presence of CO2/HCO3- in the incubation medium does not accelerate the recovery rate nor does SITS (100 microM) inhibit the recovery. Intrategumental Na+ is elevated after an acid load and amiloride (3 mM) as well as low Na+ medium interfere with recovery from the acid load indicating that a Na(+)-H+ exchanger may be present in the tegumental membrane. PMID- 2263417 TI - A confocal scanning laser microscope study of the peptidergic and serotoninergic components of the nervous system in larval Schistosoma mansoni. AB - The localization and distribution of the serotoninergic and peptidergic elements of the nervous system of larval Schistosoma mansoni have been investigated using an indirect immunofluorescence technique in conjunction with confocal scanning laser microscopy (CSLM). A range of antisera was used, raised to the biogenic amine, 5-hydroxytryptamine (5-HT, or serotonin), the vertebrate peptides pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) and to the native invertebrate peptide, FMRFamide; all these antisera were shown previously to be immunopositive in the adult worm. No immunoreactivity to 5-HT was detected in any of the larval stages, but both miracidia and cercariae were consistently immunoreactive to all 4 peptides. The peptidergic nervous system of the miracidium is relatively simple, taking the form of a central neural mass with associated paired anterior and posterior nerve tracts. The cercarial peptidergic nervous system comprises a central commissure joining paired anterior ganglia, from which emanate paired dorsal and ventral nerve tracts, which terminate at the body/tail junction. The excretory bladder region of the tail is also immunoreactive for the 4 peptides, and a fine pair of nerve tracts extends the length of the tail shaft. Immunoreactive nerve cell bodies are also evident in the midbody region of the intrasprocystic cercariae, these same structures being immunoreactive for the neuronal marker, neurone-specific enolase (NSE). The organization of the larval peptidergic nervous system is compared to that of the cholinergic nervous system and contrasted with the peptidergic system in the adult worm. The absence of immunoreactivity to 5-HT is discussed in relation to the proposed development of the aminergic nervous system upon establishment in the definitive host. PMID- 2263418 TI - Characterization of Trypanosoma congolense serodemes in stocks isolated from Chipata District, Zambia. AB - Six stocks of Trypanosoma congolense were cloned from 17 stocks isolated from Eastern Zambia and used to initiate insect-form in vitro cultures producing metacyclic trypanosomes. Serological assays were then developed using these in vitro-derived metacyclics as a reference collection of antigens. Monoclonal antibodies recognized 8 metacyclic variable antigen types (M-VATs) of one stock, T. congolense TREU 1885, representing 70-80% of that stock's M-VAT repertoire, and in an indirect fluorescent antibody test (IFAT) there were no cross-reactions between them and the metacyclic trypanosomes of the other 5 stocks. Cross protection assays between the 6 stocks in mice showed that the stocks cultured in vitro were serologically distinct. In order to facilitate serological typing for serodeme characterization, an IFAT was developed using formalin-fixed metacyclic trypanosomes to identify VAT specific immune responses using 21 day post infection antisera. The cultured stocks reacted only with their homologous antisera thus confirming the results obtained in the cross-protection assays. No cross-reactions were observed with the 6 cloned stocks and antisera against the 11 stocks of T. congolense isolated in the same area at the same time suggesting that these stocks were different from the reference collection of cultured metacyclics. Hence, at least 7 serodemes of T. congolense have been identified from the 17 stocks isolated. PMID- 2263419 TI - Avian trypanosomes in Simulium and sparrowhawks (Accipiter nisus). AB - Isolates of avian trypanosomes from nestling sparrowhawks (Accipiter nisus) and from Simulium latipes were compared by isoenzyme electrophoresis with the previously described avian trypanosomes Trypanosoma corvi and T. everetti. Simulium isolates developed into trypomastigotes in semi-defined medium at 37 degrees C confirming that they belong to the genus Trypanosoma. Cellulose acetate electrophoresis (CAE) and polyacrylamide gel electrophoresis (PAGE) methods were employed. A total of 11 enzymes was examined, of which 8 gave satisfactory results for all lysates (MDH, ICD, PGM, 6PGD, SOD, PEP I, PEP II and PEP D). The zymograms of 3 isolates from Simulium and 4 from A. nisus were similar indicating that they were the same organism and the isoenzyme patterns coincided with those of T. corvi. It is concluded that A. nisus and S. latipes are infected with T. corvi. Flagellate infections were found in the midgut, hindgut and rectum of Simulium where large numbers of epimastigotes were found in the lumen and attached to the cuticular intima of the rectal ampullae by hemidesmosomes at the distal end of an expanded flagellum. Out of 285 nestling sparrowhawks 13 (5%) were infected with trypanosomes. In view of their age and inability to preen themselves it is suggested they became infected via infected prey. PMID- 2263420 TI - Glucose transport in Acanthocheilonema viteae. AB - The uptake of glucose by Acanthocheilonema viteae was studied in vitro. The process was selective for the D-isomer and saturatable with a Km of 2 mM. The rate of glucose transport/utilization was inhibited by 2-deoxyglucose, mannose, 5 thioglucose and dipyridamole but, unlike mammalian systems, was not impaired by cytochalasin B, phloretin, phloridzin, 3-O-methylglucose and 4,6 ethylideneglucose. A potential chemotherapeutic advantage of selectively inhibiting filarial glucose transport exists for the following reasons. (1) The glucose transporter present in A. viteae was shown to be different from the one present in some mammalian systems. (2) Incubation under glucose-free conditions led to glycogen depletion, loss of motility and worm death. (3) Worms maintained in vitro for more than 18 h without glucose did not survive when implanted into gerbils. PMID- 2263421 TI - On the infracommunity structure of adult cestodes in freshwater fishes. AB - The distribution-co-occurrence and exchange of adult cestode species in two fish communities (the Bothnian Bay and Lake Yli-Kitka both in Finland) was studied. Coexistence of two or more mature cestode species in the same fish host population was zero for all fish species studied (33) except pike in the Bothnian Bay and whitefish in the lake. It was found that 60% of the fish species studied in the Bothnian Bay and 80% of the fish species studied from Lake Yli-Kitka harboured only 1 mature cestode species. Exchange of adult cestode species between the different fish species in these two fish communities was found to be as rare as coexistence. The infra-community structure of adult cestodes in freshwater fish thus turned out to be markedly different from what is known to be the situation in birds. The evolutionary explanation behind the differences is discussed. PMID- 2263422 TI - Rostellar hook morphology of Echinococcus granulosus (Batsch, 1786) from natural and experimental Australian hosts, and its implications for strain recognition. AB - An analysis of the rostellar hooks of Australian isolates of Echinococcus granulosus revealed that there was less variation in larval (metacestode) than adult characters and that metacestode characters could be measured directly from adult worms. A factor analysis indicated that two factors, one representing a contrast between number of hooks and their length, and the other representing blade lengths, were sufficient to account for 87.5% of the variance in metacestode hook measurements. These results indicate that rostellar hook morphology is not useful for discriminating strains of E. granulosus in Australia. The Tasmanian and mainland domestic strains were found to be indistinguishable using rostellar morphology. Although many of the isolates from sylvatic hosts differed from those from domestic hosts, there was not a clear separation as would be expected if two distinct strains existed. Evidence was presented to show that the morphological differences seen in sylvatic hosts could be attributed to host-induced effects, and that the previously accepted existence of two mainland strains should be investigated further. PMID- 2263423 TI - Genetic diversity and genetic differentiation in Echinococcus granulosus (Batsch, 1786) from domestic and sylvatic hosts on the mainland of Australia. AB - Enzyme electrophoresis was used to examine genetic variation within and between populations of Echinococcus granulosus from domestic and sylvatic hosts in western and eastern Australia. Substantial genetic diversity was found within all populations. There was no evidence, however, of genetic differentiation between populations from different hosts or geographic areas. When isolates were grouped into previously described domestic or sylvatic strains on the basis of rostellar hook morphology, most (94%) of the genetic variation occurred within, rather than between strains. These results conflict with the currently accepted theory of separate domestic and sylvatic strains of E. granulosus on the mainland of Australia. PMID- 2263424 TI - Genetic influences upon eosinophilia and resistance in mice infected with Mesocestoides corti. AB - The genetic influences upon host variation in eosinophilia and resistance to helminth infection, and the relationship between these parameters, was investigated in 9 inbred and 3 hybrid strains of mice infected with Mesocestoides corti. Blood, bone marrow, spleen and peritoneal fluid eosinophilia were far higher in SJL mice than in any other inbred strain. SWR, NIH, C3H and BALB/c mice were high responders to M. corti whereas CBA and 3 congenic strains sharing the B10 background (C57BL/10, B10.S, B10.G) were low responders. Some of the genes for high eosinophil responsiveness appeared to be dominant, as F1 hybrids from high and low response parental strains were intermediate to high in response to infection. SJL and NIH strains were highly susceptible to infection with M. corti, larval burdens at 21 days after infection with 100 tetrathyridia being considerably higher (greater than 1000) than all other strains. BALB/c (congruent to 700 larvae) were designated susceptible, SWR (greater than 400 larvae) were resistant and the B10 congenics (less than 400 larvae) were highly resistant. Genes influencing resistance also appeared to be dominant, as F1 hybrids between resistant and susceptible parental strains were intermediate to resistant on infection. The overall response patterns indicate a direct correlation between susceptibility to infection and high eosinophil responsiveness, but this relationship is not consistent in all strains. PMID- 2263425 TI - Two- and three-dimensional locomotion of the nematode Nippostrongylus brasiliensis. AB - Locomotion of adult Nippostrongylus brasiliensis has been studied in saline, in 0.6% agar, in sodium alginate of different viscosities and amongst sand grains in these media. In saline the nematode formed two-dimensional waves but there was little forward progression. Amongst sand grains in saline the nematode moved forwards by thrusting against sand grains, but thigmokinetic behaviour later resulted in quiescence. In 0.6% agar and in alginates of weak viscosity the nematode produced two-dimensional waves and sometimes a three-dimensional helical wave which resulted in forward movement. The formation of three-dimensional waves and the distance travelled increased with increasing viscosity up to 4% sodium alginate and also amongst sand gains in these media. In 8% sodium alginate the nematode became coiled like a spring but remained almost stationary. The three dimensional wave is formed with torsion and obtains thrust from the viscous medium. In the intestine of the host thrust will be obtained from the mucus and villi of the intestinal mucosa. The ability of this nematode to move by two- and three-dimensional undulatory propulsion is probably related to its complex ridged cuticle. Attention is drawn to the role that increased viscosity of mucus may play in entrapping nematodes during their immune rejection. PMID- 2263426 TI - The population biology of the free-living phase of Haemonchus contortus. AB - A deterministic model for the demography of the free-living stages of Haemonchus contortus is described. The model consists of three compartments: the pre infective stages, comprising the eggs and first- and second-stage larvae combined; third-stage larvae in the faeces; and third-stage larvae on the pasture. The mortality (mu j) of each of these stages was a function of temperature (K, where K = (degrees Celsius + 30)/100) of the form, mu j = a j exp [alpha j K] + b j exp [-beta j K]. The minimum time to second moult (tau) and the moulting rate thereafter (sigma) were also functions of temperature (ln [1/tau] = c1 + c2[1/K], and sigma = d1 exp [d2 K] respectively). The rate at which L3 larvae migrated out of the faeces was treated as a constant (0.165/larva/day). PMID- 2263427 TI - Short course chemotherapy for childhood tuberculosis. AB - A prospective study, with an attempted 24-month-post-treatment follow-up, of children with tuberculosis (TB) treated with short course chemotherapy (SCC) for 6 months was carried out because published experience of SCC in childhood TB was limited. All children in Port Moresby diagnosed as having TB between November, 1984, and November, 1986, entered the trial. Of the 639 children 165 (26%) were younger than 2 years old. Of these, 227 (35%) had extrapulmonary TB (peripheral lymph node, 110; central nervous system, 43; abdominal, 27; miliary, 16; bone and joint, 11; pleural, 11; polyserositis, 9). Clinical response to SCC was rapid. Adverse drug reactions occurred in 15 (2%), mainly to streptomycin. Twelve (2%) died, 38 (6%) transferred out and 145 (28% of the 518 who did not die, transfer or live too far from a treatment centre) defaulted. Three hundred seventy-three (58%) completed a 2-month course of daily rifampin, isoniazid, pyrazinamide and streptomycin followed by a 4-month course of twice weekly rifampin and isoniazid. A further 71 (11%) had their treatment modified because of their distance from a treatment center. Only 70 (19%) of the 373 children available for post-treatment follow-up attended the every-3-month follow-up visits for 24 months, although 223 (60%) attended one or more of the follow-up visits. Seven of the 373 children relapsed, mostly within 3 months. Five of these children had been irregular with their treatment. SCC for childhood TB is safe and effective for pulmonary and extrapulmonary disease. PMID- 2263428 TI - A randomized trial of fully intermittent vs. daily followed by intermittent short course chemotherapy for childhood tuberculosis. AB - Fully intermittent short course chemotherapy regimens have been used successfully in adults but not in children. We report the results on 76 children with tuberculosis, excluding central nervous system tuberculosis and primary pulmonary complex. Isoniazid, rifampin and pyrazinamide were used for treatment. They were randomly allocated to Regimen A (52 doses) and Regimen B (94 doses). Overall efficacy of both schedules was greater than 95% in 27 children with lymphatic, 43 with pulmonary and 6 with disseminated tuberculosis. Compliance in 10 children after 2 to 4 months of therapy was poor because rapid improvement was mistaken by parents for cure. Two children died, probably of underlying lung disease. Follow up for up to 2 years did not reveal any case of relapse or recurrence of the disease. Therapy for 6 months involving administration of only 52 or 94 doses of drugs was found to be economical, effective and safe for treating children with tuberculosis. PMID- 2263429 TI - Beta-2-microglobulin concentrations in pediatric human immunodeficiency virus infection. AB - Serum concentrations of beta-2-microglobulin (B2-M) were correlated with disease outcome in 40 children infected by the human immunodeficiency virus. Serum B2-M serum concentrations below 3.0 mg/100 ml or decreasing concentrations were indicative of a stable disease course but were also noted preterminally in lymphopenic children. Of 20 patients with B2-M concentrations above 3.0 mg/liter, 12 had a progressive disease course and 8 remained stable. In the latter 8 patients the B2-M values decreased with time. Elevated B2-M concentrations were also noted in infants younger than 1 year of age and denoted active human immunodeficiency virus infection. B2-M serum concentrations are a useful prognostic marker in human immunodeficiency virus-infected children. PMID- 2263430 TI - Cefotaxime and aminoglycoside treatment of meningitis caused by gram-negative enteric organisms. AB - We reviewed cases of Gram-negative enteric bacillary meningitis in infants and children treated with cefotaxime at Texas Children's Hospital from January, 1984, through June, 1989. Seventeen of 20 children had an underlying condition predisposing to the development of meningitis. The etiologic organisms in these 20 children (2 days to 12 years old; median, 12 days old) were Klebsiella sp, 9; Escherichia coli, 4; Enterobacter cloacae, 3; Citrobacter diversus, 2; other, 2. With the exception of one isolate of Acinetobacter, all isolates were susceptible to cefotaxime. In addition to cefotaxime 17 children received an aminoglycoside intravenously. Children with meningitis caused by Klebsiella sp. or non Klebsiella organisms received cefotaxime for 31 +/- 14 and 37 +/- 17 days, respectively. Aminoglycosides were administered for 16 +/- 10 days in both groups. Five children in each group also received intraventricular doses (1 to 25) of an aminoglycoside (9) or colistimethate (1). The mean durations of positive lumbar, ventricular cerebrospinal fluid or brain abscess cultures were 5.8 +/- 4.7 and 7.2 +/- 5.0 days after start of therapy in the Klebsiella and non Klebsiella meningitis patients, respectively. Only three children were normal at the time of discharge or follow-up. Gram-negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against Gram-negative enterics, in part as a result of the predisposing conditions resulting in the development of this infection. PMID- 2263431 TI - Utility of collecting blood cultures through newly inserted intravenous catheters. AB - We prospectively examined the utility of obtaining blood cultures through newly inserted intravenous catheters in 99 children who required both a blood culture and placement of an intravenous catheter. Two blood cultures were collected from each patient, one through a freshly inserted intravenous catheter and another through a butterfly needle at a separate venipuncture site. A standardized technique of skin preparation with povidone-iodine was used. The rate of contamination was 1.0% (95% confidence intervals, 0 to 3.0%) for each method. Ten patients had blood cultures yielding true pathogens; in five of these bacteremic children, only one of two sets of blood cultures was positive. We conclude that blood cultures can be collected through freshly placed intravenous catheters without increasing the risk of contamination. These results also raise the possibility that obtaining two blood cultures instead of a single culture may improve the detection of bacteremia in children. PMID- 2263432 TI - A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience. AB - Records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates. Using a modification of objective Centers for Disease Control criteria to define sepsis, we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis. The sepsis rate for infants less than or equal to 30 days of age was 2.7 cases/1000 live births, with a mortality rate from sepsis of 15.9%. There was an increase in sepsis due to commensal species (CS) over the period (P less than 0.007). The number of infants in the nursery who developed sepsis when more than 30 days of age also increased (P less than 0.002), as did the rate of sepsis from CS in this group (P less than 0.001). Isolation of CS from the blood with fulfillment of the modified Centers for Disease Control criteria was associated with a 13.7% mortality rate, whereas isolation of CS without fulfillment was associated with a 4% rate (P less than 0.01). PMID- 2263433 TI - Management of asymptomatic, term gestation neonates born to mothers treated with intrapartum antibiotics. AB - Intrapartum antibiotics are frequently administered to parturient women for suspected chorioamnionitis to treat infection in the mother and to prevent or treat infection in the baby. We sent a questionnaire to the 150 United States fellowship program directors in neonatology and pediatric infectious disease, focusing on recommendations for evaluation and therapy of apparently healthy, pretreated, term gestation infants. Eighty-three (55%) of the completed responses were analyzed. Sixteen (19%) respondents do no initial laboratory evaluation but simply observe the baby, 65 (78%) take a complete blood count as well as a platelet count, 59 (71%) obtain blood cultures, 41 (49%) check urine antigen for Group B Streptococcus (GBS) and 23 (28%) perform a lumbar puncture. Only 39% of respondents would begin antibiotic therapy for all pretreated infants. If the evaluation were unremarkable 65 directors would treat for less than or equal to 3 days. If only the urine GBS antigen were positive 47 would treat for greater than or equal to 7 days, while if an elevated immature neutrophil:total neutrophil ratio were the sole abnormality 19 would treat for greater than or equal to 7 days. Forty-four respondents thought that a combination of an elevated immature neutrophil:total neutrophil ratio and a positive urine GBS antigen should always be considered indicative of bacteremia. Given a different scenario, that of a mother treated with intrapartum antibiotics because of a positive cervical culture for GBS and a risk factor (e.g. temperature greater than or equal to 38 degrees C), 58 respondents would begin antibiotics. There is no consensus regarding management of pretreated, healthy appearing, term gestation neonates. PMID- 2263434 TI - Group A beta-hemolytic streptococcal vulvovaginitis in prepubertal girls: a case report and review of the past twenty years. PMID- 2263435 TI - Evaluation of the Technicon H-1 hematology analyzer in febrile children. PMID- 2263436 TI - Saccharomyces cerevisiae infection in a patient with acquired immunodeficiency syndrome. PMID- 2263437 TI - Disseminated mucormycosis in an infant with methylmalonicaciduria. PMID- 2263438 TI - Fetal varicella syndrome. PMID- 2263439 TI - Prethyroidal swelling in mumps. PMID- 2263440 TI - Migratory polyarthritis in a nine-year-old girl. PMID- 2263441 TI - Treatment of brucellosis. PMID- 2263442 TI - Risk of subacute sclerosing panencephalitis from measles vaccination. PMID- 2263443 TI - Group B streptococcal antigenuria in an asymptomatic newborn. PMID- 2263444 TI - Enhancement of foreign gene expression by a dicot intron in rice but not in tobacco is correlated with an increased level of mRNA and an efficient splicing of the intron. AB - The first intron of castor bean catalase gene, cat-1 was placed in the N-terminal region of the coding sequence of the beta-glucuronidase gene (gusA) and the intron-containing gusA was used with the cauliflower mosaic virus (CaMV) 35S promoter. Using this plasmid, pIG221, the effect of the intron on expression of beta-glucuronidase (GUS) activity was examined in transgenic rice calli and plants (a monocotyledon), and transgenic tobacco plants (a dicotyledon). The intron-containing plasmid increased the level of GUS enzyme activity 10 to 40 fold and 80 to 90-fold compared with the intronless plasmid, pBI221, in transgenic rice protoplasts and transgenic rice tissues, respectively. In contrast, the presence of the intron hardly influenced the expression of the GUS activity in transgenic tobacco plants. Northern blot analysis showed that the catalase intron was efficiently spliced in rice cells while transgenic tobacco plants contained both spliced and unspliced gusA transcripts in equal amounts. Furthermore, the level of the mature gusA transcript in transformed rice calli was greatly increased in the presence of the intron. The catalase intron was removed at the same splice junctions in transgenic rice and tobacco plants. These findings indicate that the stimulating effect of the intron on GUS expression is correlated with an efficient splicing of pre-mRNA and an increased level of mature mRNA. PMID- 2263445 TI - Detection of single base mismatches of thymine and cytosine residues by potassium permanganate and hydroxylamine in the presence of tetralkylammonium salts. AB - In the presence of tetramethylammonium chloride, potassium permanganate specifically modifies mismatched thymines. Similarly, the modification of mismatched cytosines by hydroxylamine was enhanced by tetraethylammonium chloride. Modification followed by piperidine cleavage permits specific identification of the T and C mismatches and by extension, when the opposite DNA strand is analyzed, of A and G mismatches as well. These reactions can be performed conveniently with DNA immobilized on Hybond M-G paper. We describe conditions that exploit these reactions to detect mismatches, e.g. point mutations or genetic polymorphisms, using either synthetic oligonucleotide probes or PCR amplification of specific genomic DNA sequences. PMID- 2263446 TI - Conversion of aminoacylation specificity from tRNA(Tyr) to tRNA(Ser) in vitro. AB - The discrimination mechanism between tRNA(Ser) and tRNA(Tyr) was studied using various in vitro transcripts of E. coli tRNATyr variants. The insertion of only two nucleotides into the variable stem of tRNA(Tyr) generates serine charging activity. The acceptor activities of some of the tRNA(Tyr) mutants with insertions in the long variable arm were enhanced by changes in nucleotides at positions 9 and/or 20B, which are possible elements for dictating the orientation of the long variable arm. These findings suggest that the long variable arm is involved in recognition by seryl-tRNA synthetase in spite of sequence and length variations shown within tRNA(Ser) isoacceptors, and eventually serves as a determinant for selection from other tRNA species. Changing the anticodon from GUA to the serine anticodon GGA resulted in a marked decrease in tyrosine charging activity, but this mutant did not show any serine charging activity. The discriminator base, the fourth base from the 3' end of tRNA, was also important for aminoacylation with tyrosine. Complete specificity change in vitro was facilitated by insertion of three nucleotides into the variable arm plus two nucleotide changes at positions 9 and 73. PMID- 2263447 TI - The self-cleaving domain from the genomic RNA of hepatitis delta virus: sequence requirements and the effects of denaturant. AB - The sequence requirements for self-cleavage of hepatitis delta virus genomic RNA were examined using precursor RNAs which were labeled at either the 5' or 3' ends and progressively deleted from the unlabeled end. In the presence of 50% formamide, which enhances self-cleavage in 2 mM MgCl2 at 37 degrees C, 84 nucleotides (nt) 3' of the break site were required. In the absence of formamide the minimum was reduced to 82 nt. Under both sets of conditions, precursors with 1 nt 5' to the break site cleaved. These results allowed two condition-dependent minimal domains for self-cleavage to be defined. However, in the absence of formamide, sequences flanking the minimal domain inhibited cleavage, possibly through involvement in the formation of non-cleaving structures. These data are consistent with the idea that cleavage in vivo could be regulated by alternative RNA structures. PMID- 2263448 TI - Long range restriction analysis of the bovine casein genes. AB - Pulsed field gel electrophoresis (PFGE) was used to analyse the organization of the bovine alpha s1, alpha s2, beta and kappa casein genes. High molecular weight DNA was prepared from fibroblasts and lymphocytes embedded in agarose and was digested with the restriction endonucleases Clal, Sall, Smal, Xhol. The digestion products were separated by PFGE, transfered to nitrocellulose filters and hybridized to probes corresponding to the cDNAs of the four bovine casein genes. The casein genes were demonstrated to be physically linked within a region of 300 kb, represented by two adjacent Xhol fragments in fibroblasts and by a single fragment in lymphocytes. A restriction map of the casein locus was derived and the order of the genes was shown to be kappa, alpha s2, beta, alpha s1. PMID- 2263449 TI - Multiple protein factors bind to a rice glutelin promoter region. AB - Our goal is to identify cis-acting elements in the regulatory region of the major seed storage protein gene in rice. A glutelin gene (pGL5-1) has been cloned by screening a rice genomic DNA library with synthetic oligonucleotides and with an amplified DNA fragment. A transient expression assay using immature rice seeds shows that its 5' flanking sequence can direct the synthesis of beta glucuronidase (GUS) when fused upstream of the GUS coding region. Gel-retardation assays were performed to study protein-DNA interactions between putative regulatory sequences of pGL5-1 and nuclear proteins from immature rice seeds. We demonstrate that at least six protein-DNA complexes are formed between the 5' flanking sequence of pGL5-1 (-677 to -45) and nuclear protein factors. By subsequent DNase I-footprinting analyses we defined several protein-binding regions. Two of the protein-binding sequences contain the TGAGTCA motif, which is also present in the -300 element found in the 5' flanking sequences of several storage protein genes of other crop plants, and to which the transcription factors jun and GCN4 bind. PMID- 2263450 TI - COUP-TF gene: a structure unique for the steroid/thyroid receptor superfamily. AB - Two different genomic genes for the COUP-transcription factor, COUP-TF I and COUP TF II, have been isolated from a human cosmid genomic library using a [32P] labeled cDNA probe. Data obtained from Southern blot analysis of these cosmid clones indicated that two closely related genes exist in the human genome and have a similar genomic organization. The genes are similar in the hormone and DNA binding domains but diverge from one another in the N-terminal region. Using DNA sequencing and polymerase chain reaction (PCR) techniques we have determined that the structure of COUP-TF I consists only of three exons and two introns. Surprisingly, both zinc fingers (i.e., F1 and F2) are located in the first exon. Therefore, COUP-TF I is unique among the members of the steroid/thyroid hormone receptor superfamily which have been described to date. PMID- 2263451 TI - Interaction of the isolated domain II/III of Thermus thermophilus elongation factor Tu with the nucleotide exchange factor EF-Ts. AB - The middle and C-terminal domain (domain II/III) of elongation factor Tu from Thermus thermophilus lacking the GTP/GDP binding domain have been prepared by treating nucleotide-free protein with Staphylococcus aureus V8 protease. The isolated domain II/III of EF-Tu has a compact structure and high resistance against tryptic treatment and thermal denaturation. As demonstrated by circular dichroism spectroscopy, the isolated domain II/III does not contain any alpha helical structure. Nucleotide exchange factor, EF-Ts, was found to interact with domain II/III, whereas the binding of aminoacyl-tRNA, GDP and GTP to this EF-Tu fragment could not be detected. PMID- 2263452 TI - Structural and functional analyses of a yeast mitochondrial ribosomal protein homologous to ribosomal protein S15 of Escherichia coli. AB - We have purified a small subunit mitochondrial ribosomal protein, MRPS28p, from the yeast, Saccharomyces cerevisiae. Sequence from the amino terminus of MRPS28p was used to design a degenerate oligonucleotide that was complementary to the MRPS28 gene. The MRPS28 gene was isolated and its sequence determined. The MRPS28 sequence encodes a 28 kDa protein that has a region of homology with ribosomal protein S15 of E. coli. This region spans the entire length of the E. coli protein, but as MRPS28p is larger, includes only the portion of the MRPS28p sequence from amino acids 150 to 238. Based on this homology, we predict that MRPS28p, like E. coli S15, interacts directly with small subunit rRNA and functions as an early protein in ribosome assembly. Cells carrying a disrupted chromosomal copy of MRPS28 are unable to respire and spontaneously lose portions of their mitochondrial genomes at a high frequency. These phenotypes are consistent with an essential role for MRPS28p in the assembly and/or function of the mitochondrial ribosome. PMID- 2263453 TI - Characterization of the VirG binding site of Agrobacterium tumefaciens. AB - Expression of Agrobacterium tumefaciens virulence (vir) genes is dependent on the presence of a conserved 'vir box' sequence in their 5' nontranscribed regions. The location and number of these sequences vary considerably in different vir genes. Site-directed mutagenesis was used to identify the functional vir box(es) of virB, virC and virD. For virB expression both vir box B1 and B2 are required but only the vir box B1 is absolutely essential. Of the five vir boxes of virC and virD two are required for virC expression while only one vir box is required for virD expression. To investigate the minimum sequences necessary for vir gene induction a deletion derivative of virE that lacks the vir box region was used. This mutant is not induced by acetosyringone. The inducibility of this promoter was restored when a synthetic deoxyoligonucleotide dGTTTCAATTGAAAC was introduced at a location analogous to that of the wild type vir box sequence. Mutational analysis indicate that the functional vir box sequence is 14 residues in length, contains a dyad symmetry and has the consensus sequence d ryTncAaTTGnAaY [corrected] (r = purine, y = pyrimidine). PMID- 2263454 TI - Complete sequence of the extrachromosomal rDNA molecule from the ciliate Tetrahymena thermophila strain B1868VII. AB - The recent development of rDNA vectors for transformation of Tetrahymena combined with improved microinjection technology should lead to a renewed interest in this organism. In particular, the rDNA itself constitutes an attractive system for biochemical studies. The rDNA is amplified to a level of 2% of the total DNA and exists as extrachromosomal molecules. Furthermore, the rDNA is homogeneous in sequence because it is derived from a single gene during sexual reorganization. In order to facilitate studies of this molecule, we report here a compilation of previously published sequence information together with new sequence data that completes the entire sequence of the 21 kb rDNA molecule. PMID- 2263455 TI - Detection of a specific mitochondrial DNA deletion in tissues of older humans. AB - Using PCR, we found that normal heart muscle and brain from adult human individuals contain low levels of a specific mitochondrial DNA deletion, previously found only in patients affected with certain types of neuromuscular disease. This deletion was not observed in fetal heart or brain. Experimental tests support the idea that the deletion exists in vivo in adult mitochondria and is not an in vitro artifact of PCR. Our data provide direct experimental support for the idea that accumulation of mitochondrial DNA deletions may be important in aging. PMID- 2263456 TI - VirD2 gene product from the nopaline plasmid pTiC58 has at least two activities required for virulence. AB - Virulence genes virD1 and virD2 are required for T-DNA processing in Agrobacterium tumefaciens. The regions within virD2 contributing to T-DNA processing and virulence were investigated. Some insertional mutations in virD2 prevented T-DNA border endonucleolytic cleavage and produced an avirulent phenotype. However, a non-polar insertion immediately after bp 684 of the 1344 bp open reading frame of virD2 did not inhibit endonucleolytic cleavage but still caused a loss of virulence. This suggested that in addition to T-DNA border cleaving activity, the VirD2 protein has another virulence function which resides in the C-terminal half of the protein. Comparative nucleotide sequence analyses of virD2 showed that the first 684 bp were 81% homologous to virD2 of an octopine Ti plasmid whereas the remaining 660 bp were only 44% homologous. A plasmid containing the virD region from octopine Ti plasmid could restore both virulence and processing to a nopaline virD2 mutant. No complementation resulted when a nopaline virD2 clone containing a region similar to eukaryotic nuclear envelope transport sequences was deleted from the 3' end. These results suggest that virD1 and only the first half of virD2 are required to encode for the T-DNA processing endonuclease, and that the 3'-half of virD2 encodes a function separate from endonuclease activity that is required for virulence. PMID- 2263457 TI - Increased dosage of the MSN1 gene restores invertase expression in yeast mutants defective in the SNF1 protein kinase. AB - The SNF1 protein kinase is required for expression of the invertase gene in response to glucose deprivation in Saccharomyces cerevisiae. We selected for genes that in multicopy suppress the invertase defect of temperature-sensitive snf1 mutants. Increased dosage of the MSN1 gene restores high-level, regulated invertase expression in snf1-ts mutants, and disruption of MSN1 in the wild type reduces invertase expression a fewfold. MSN1 gene dosage does not affect SNF1 protein kinase activity in vitro. MSN1 encodes a 43-kilodalton protein, and a MSN1-beta-galactosidase fusion protein was localized in the nucleus. A LexA-MSN1 fusion protein, when bound to a lexA operator, activates transcription of an adjacent promoter. In vitro synthesized MSN1 protein exhibits weak, nonspecific DNA-binding activity. PMID- 2263458 TI - A simple and sensitive method for determining transcription initiation site: identification of two transcription initiation sites in rat group II phospholipase A2 gene. AB - We developed a simple and sensitive method for assigning transcriptional initiation sites, and applied it to characterize the transcriptional unit of rat group II phospholipase A2 (PLA2) gene. Our method involves the primer extension reaction followed by detection of its products by hybridization. Using this method, we were able to map two transcriptional initiation sites on the nucleotide sequence of the core promoter region of PLA2 gene with one-base resolution without any difficulties. PMID- 2263459 TI - RNA helicase: a novel activity associated with a protein encoded by a positive strand RNA virus. AB - Most positive strand RNA viruses infecting plants and animals encode proteins containing the so-called nucleotide binding motif (NTBM) (1) in their amino acid sequences (2). As suggested from the high level of sequence similarity of these viral proteins with the recently described superfamilies of helicase-like proteins (3-5), the NTBM-containing cylindrical inclusion (CI) protein from plum pox virus (PPV), which belongs to the potyvirus group of positive strand RNA viruses, is shown to be able to unwind RNA duplexes. This activity was found to be dependent on the hydrolysis of NTP to NDP and Pi, and thus it can be considered as an RNA helicase activity. In the in vitro assay used, the PPV CI protein was only able to unwind double strand RNA substrates with 3' single strand overhangs. This result indicates that the helicase activity of the PPV CI protein functions in the 3' to 5' direction (6). To our knowledge, this is the first report on a helicase activity associated with a protein encoded by an RNA virus. PMID- 2263460 TI - Structural organization and differential expression of rice alpha-amylase genes. AB - Rice alpha-amylases are encoded by a multigene family that has previously been classified into 5 hybridization groups. DNA sequence and Southern blot analysis identified three genes (RAmy1A, RAmy1B and RAmy1C) in Group 1 with DNA sequence identity of at least 90%. Hybridization Group 2 is represented by only one gene, RAmy3D, which is identical to a previously characterized cDNA, pOS137. RAmy3D is physically linked to the sole representative of Group 5, RAmy3E. The identity between these two genes is 81.4% in the coding region but less than 50% in the 5' and 3' flanking regions. Northern blot analysis and RNA-PCR were used to detect the expression of alpha-amylase genes in various tissues. Alpha-amylase mRNA was abundant in germinating seeds and callus. Some genes were also expressed at much lower levels in roots, young leaves and immature seeds. RAmy1A and RAmy3E were expressed in all tissues while RAmy3D was expressed in all tissues except the immature seeds. RAmy1B was weakly expressed only in callus. RAmy1A transcript was most abundant in the germinating seeds, while RAmy3D and RAmy3E transcripts were most abundant in callus and immature seeds, respectively. PMID- 2263461 TI - Ultrastructure of transcriptionally competent chromatin. AB - We have examined a salt-soluble, transcriptionally competent gene-enriched fraction of chicken erythrocyte chromatin and compared it to bulk chromatin using the unique microanalytical capabilities of Electron Spectroscopic Imaging (ESI). The salt-soluble fraction is enriched 48 fold in beta-globin gene sequences and is also enriched in histones that are post-synthetically modified, including acetylation and ubiquitination. Differences between the two fractions are also apparent in the distribution of the two major forms of nucleoprotein structures, including (1) particles which present a circular profile and possess protein and DNA content nearly identical to that of the canonical nucleosome and account for 89% of particles in the bulk fraction but account for only 66% of the particles in the competent fraction, and (2) u-shaped particles which possess about 20% less protein mass than particles of circular profile and are about 10x more prevalent in the transcriptionally competent fraction than in the bulk. Additionally, elongated particles with protein and DNA content similar to the u shaped objects are also seen in the competent fraction. PMID- 2263462 TI - Isolation and characterization of a variant dihydrofolate reductase cDNA from methotrexate-resistant murine L5178Y cells. AB - Dihydrofolate reductase (DHFR) cDNA sequences were isolated from a methotrexate resistant mouse L5178Y cell line previously shown to contain methotrexate resistant dihydrofolate reductase enzyme activity. Specifically-primed reverse transcription products were amplified using the polymerase chain reaction and then cloned into a mammalian expression plasmid. Candidate clones were identified by restriction analysis and then functionally tested by transfection into mouse 3T3 fibroblasts, selecting for methotrexate-resistant colonies. Sequence analysis of the cDNA clones demonstrated the substitution of tryptophan (TGG) in place of the wild-type phenylalanine (TTC) at codon 31. Sequencing of PCR-amplified genomic DNA extracted from the drug-resistant L5178Y cells confirmed the tryptophan codon at position 31. Transfection of mammalian tissue culture cells with expression plasmids containing the trp31 DHFR sequence resulted in substantial methotrexate-resistant colony formation. Recombinant trp31 DHFR enzyme activity expressed in stably-transfected Chinese hamster ovary cells was approximately 20-fold less sensitive to methotrexate inhibition than wild-type mouse DHFR enzyme activity. We conclude that the cloned Trp31 DHFR sequence encodes an enzyme substantially resistant to methotrexate which confers a drug resistance phenotype to cells in which it is expressed. PMID- 2263463 TI - Preparation and characterization of yeast nuclear extracts for efficient RNA polymerase B (II)-dependent transcription in vitro. AB - We present a reproducible method for the preparation of nuclear extracts from the yeast Saccharomyces cerevisiae that support efficient RNA polymerase B (II) dependent transcription. Extracts from both a crude nuclear fraction and Percoll purified nuclei are highly active for site-specific initiation and transcription of a G-free cassette under the Adenovirus major late promoter. At optimal extract concentrations transcription is at least 5 times more efficient with the yeast extracts than with HeLa whole cell extracts. We show that the transcriptional activity is sensitive to alpha-amanitin and to depletion of factor(s) recognizing the TATA-box of the promoter. The in vitro reaction showed maximal activity after 45 min, was very sensitive to Cl-, but was not affected by high concentrations of potassium. We find that the efficiency of in vitro transcription in nuclear extracts is reproducibly high when spheroplasting is performed with a partially purified beta 1,3-glucanase (lyticase). Therefore a simplified method to isolate the lyticase from the supernatant of Oerskovia xanthineolytica is also presented. PMID- 2263464 TI - Structural analysis of the 5' domain of the HeLa 18S ribosomal RNA by chemical and enzymatic probing. AB - The secondary structure of HeLa 18S rRNA was investigated by a combination of chemical and enzymatic probing techniques. Using four chemical reagents (DMS*, kethoxal, DEPC and CMCT) which react specifically with unpaired bases and two nucleases (RNase T1 and cobra venom nuclease) which cleave the ribopolynucleotides at unpaired guanines and helical segments, we have analyzed the secondary structure of the 5' domain of 18S rRNA isolated from HeLa 40S ribosomal subunits. The sites at which chemical modifications and nuclease cleavages occurred were identified by primer extension using synthetic deoxyoligonucleotides and reverse transcriptase. These studies led to the deduction of an intra-RNA pairing pattern from the available secondary structure models based on comparative sequence analysis. Apart from the general canonical pairing we have identified noncanonical U-U, G-A, A-G, A-C, C-A and G-G pairing in HeLa 18S rRNA. The differential reactivity of bases to chemical reagents has enabled us to predict the possible configuration of these bases in some of the noncanonical pairing. The absence of chemical reactivities and cobra venom nuclease sensitivity in the terminal loops of helices 6 and 12 indicate a tertiary interaction unique to HeLa 18S rRNA. We have confirmed the existence of the complex tertiary folding recently proposed (Gutell and Woese 1990 Proc. Natl. Acad. Sci. 87, 663-667) for the universally conserved helix 19 in HeLa 18S rRNA. The complementarity of chemical modifications and enzymatic cleavages provided experimental evidence for the proposal of a model structure for the 655 nucleotides of the 5' domain of HeLa 18S rRNA. PMID- 2263465 TI - rRNA genes from the lower chordate Herdmania momus: structural similarity with higher eukaryotes. AB - Ascidians, primitive chordates that have retained features of the likely progenitors to all vertebrates, are a useful model to study the evolutionary relationship of chordates to other animals. We have selected the well characterized ribosomal RNA (rRNA) genes to investigate this relationship, and we describe here the cloning and characterization of an entire ribosomal DNA (rDNA) tandem repeat unit from a lower chordate, the ascidian Herdmania momus. rDNA copy number and considerable sequence differences were observed between two H. momus populations. Comparison of rDNA primary sequence and rRNA secondary structures from H. momus with those from other well characterized organisms, demonstrated that the ascidians are more closely related to other chordates than invertebrates. The rDNA tandem repeat makes up a larger percentage (7%) of the genome of this animal than in other higher eukaryotes. The total length of the spacer and transcribed region in H. momus rDNA is small compared to most higher eukaryotes, being less than 8 kb, and the intergenic spacer region consists of smaller internal repeats. Comparative analysis of rDNA sequences has allowed the construction of secondary structures for the 18S, 5.8S and 26S rRNAs. PMID- 2263466 TI - Antigen expression from the ribosomal DNA repeat unit of Giardia intestinalis. AB - The amitochondrial human intestinal parasite Giardia intestinalis is regarded to be the most ancient living example of single-celled eukaryotes and should display primitive features of pre-metazoan gene regulation. Characterization of E. coli clones which express Giardia antigens from plasmid vectors has revealed that an antigen is encoded by the rDNA repeat unit from the strand complementary to that encoding the rRNAs. The open reading frame (ORF) originates in the spacer region between the small (SS) and large (LS) subunit rRNA genes and terminates within the LS rRNA gene. The promoter region of this ORF has characteristics of both RNA polymerase (pol) II and pol III regulatory sequences, suggestive of gene regulation before these different promoter types evolved. The rDNA repeat unit is located on multiple chromosomal sites which are different in each isolate, although the electrophoretic karyotypes appear very stable in Giardia from both human and animal sources. PMID- 2263468 TI - Developmental regulation of the human zeta globin gene in transgenic mice. AB - We have characterized the expression of the human zeta (zeta) gene, which encodes an embryonic alpha-like globin, in transgenic mice. We find that a 777 base pair fragment spanning erythroid specific hypersensitive site II (HSII) from the distal 5. region of the human beta globin gene cluster potentiates expression of the zeta globin gene. In the absence of the HSII fragment, no zeta expression is observed. Expression of the human zeta gene in mice parallels expression of a murine embryonic alpha-like globin gene (x). Thus, expression of the human zeta gene in mice requires linkage to an erythroid-specific enhancer sequence, but the presence of the enhancer does not affect the developmental regulation of the transgene. Our results indicate that the factors involved in switching from embryonic to adult alpha globin gene expression during development are evolutionarily conserved, and suggest that the transgenic mouse is an in vivo system in which the requirements for the developmental switch in alpha globin gene expression can be analyzed in detail. PMID- 2263467 TI - Binding of the bacteriophage T4 regA protein to mRNA targets: an initiator AUG is required. AB - Bacteriophage T4 regA protein translationally represses the synthesis of a subset of early phage-induced proteins. The protein binds to the translation initiation site of at least two mRNAs and prevents formation of the initiation complex. We show here that the protein binds to the translation initiation sites of other regA-sensitive mRNAs. Analysis of mRNA binding by filtration and nuclease protection assays shows that AUG is necessary but not sufficient for specific binding of regA protein to its mRNA targets. Anticipating the need for large quantities of regA protein for structural studies to further define the regA protein-RNA ligand interaction, we also report cloning the regA gene into a T4 overexpression system. The expression of regA protein in uninfected E. coli is lethal, so in our system regA driven by a strong T7 promoter is sequestered in a T4 phage until 'induction' by phage infection is desired. We have replaced the regA sensitive wild-type ribosome binding site with a strong insensitive ribosome binding site at an optimal distance from the regA initiation codon for maximizing expression. We have obtained large amounts of regA protein. PMID- 2263469 TI - Characterization of TPI gene expression in isogeneic wild-type and gcr1-deletion mutant strains of Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae the enzymes of glycolysis constitute 30-60 percent of the soluble protein. GCR1 gene function is required for high level glycolytic gene expression. We have undertaken a biochemical and genetic characterization of TPI, a gene affected by gcr1 lesions. Northern analysis showed that steady-state levels of TPI transcripts are severely reduced in gcr1 mutant strains. However, primer extension experiments revealed that TPI transcripts isolated from wild type and gcr1 mutant strains have identical 5' ends. To map the 5' boundary of TPI controlling region, we employed a TPI::lacZ gene fusion carrying 3.5 kb 5' to the translational start of the TPI structural gene. Nuclease Bal31 deletion analysis demonstrated that sequences sufficient for high level expression of TPI reside within 392 nucleotides preceding the start of the structural gene. We have identified GRF1/RAPI/TUF-binding site positioned 339 to 349 bp 5' to the translation start of TPI. DNA band shift assays were carried out with wild-type and gcr1 deletion mutant strains, and similar patterns of band shifting were observed. PMID- 2263470 TI - Unique organization of the human BCR gene promoter. AB - The promoter of the human BCR gene, regulating the transcription of the chimeric BCR/ABL mRNA in leukemia, has been isolated and characterized. A region of 1.1 kb immediately 5' to the transcription start site was analyzed in detail by sequencing, DNase 1 footprinting, gel retardation and functional studies. These experiments localized a minimal promoter to a 650 bp sequence, composed of 270 bp of 5' flanking sequences and 380 bp of exon 1 transcribed sequences. The promoter region includes a TTTAA box, one Sp1 site and a novel protein-binding sequence absolutely necessary for efficient transcription in vivo. Six additional protein binding regions were identified more to the 5'. Of these, one is found in an inverted repeat in the 3' coding and splice donor region of BCR exon 1. PMID- 2263471 TI - Synthesis and enzymatic polymerisation of 5-amino-1-(2'-deoxy-beta-D ribofuranosyl)imidazole-4-carboxamide-5'- triphosphate. AB - The chemical synthesis of 5-amino-1-(2'-deoxy-beta-D-ribofuranosyl)imidazole-4 carboxamide, referred to as dZ, and of its 5'-triphosphate derivative (dZTP), from 2'-deoxyinosine is described. The polymerisation of dZTP using terminal deoxynucleotidyltransferase to give a homopolymer is also presented. PMID- 2263472 TI - Sequence of the PB2 homolog of influenza C/Berlin/1/85. PMID- 2263473 TI - Complete nucleotide sequence of a pigeon alpha-globin cDNA. PMID- 2263474 TI - Nucleotide sequence of the DURM gene coding for a positive regulator of allophanate-inducible genes in Saccharomyces cerevisiae. PMID- 2263475 TI - Nucleotide sequence of RAD4 gene of Saccharomyces cerevisiae that can be propagated in Escherichia coli without inactivation. PMID- 2263476 TI - Nucleotide sequence of the Corynebacterium glutamicum trpE gene. PMID- 2263477 TI - Nucleotide and deduced amino acid sequence of an actin cDNA clone from Plasmodium falciparum. PMID- 2263478 TI - Nucleotide sequence of a human cannabinoid receptor cDNA. PMID- 2263479 TI - A mouse cDNA sequence for epididymal androgen-regulated proteins related to glutathione peroxidase. PMID- 2263480 TI - Glycerol-3-phosphate dehydrogenase homologue from Schizosaccharomyces pombe. PMID- 2263481 TI - The cDNA derived primary structure of two distinct legumin A subunit precursors from field bean (Vicia faba L.). PMID- 2263482 TI - The MYO1 gene from Saccharomyces cerevisiae: its complete nucleotide sequence. PMID- 2263483 TI - Nucleotide sequence of a heat-shock and ripening-related cDNA from tomato. PMID- 2263484 TI - Genomic sequence of the Chinese hamster MT I gene. PMID- 2263485 TI - Nucleotide sequence of a full length cDNA clone encoding the deoxyribonuclease I from the rat parotid gland. PMID- 2263486 TI - Nucleotide and deduced amino acid sequence of a murine cDNA clone encoding one member of the hsp65 multigene family. PMID- 2263487 TI - cDNA and deduced amino acid sequence of a novel cytochrome P-450 from female rat liver mRNA with high homology to P-450 IIC family. PMID- 2263489 TI - Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4. PMID- 2263488 TI - Nucleotide sequence of full length cDNA for a scallop striated muscle myosin heavy chain. PMID- 2263490 TI - Nucleotide sequence of ovine interleukin-1 beta. PMID- 2263491 TI - Nucleotide sequence of the tamarillo mosaic virus coat protein gene. PMID- 2263492 TI - cDNA and protein sequence of bovine lactoferrin. PMID- 2263493 TI - Coding sequence of human placenta cofilin cDNA. PMID- 2263495 TI - Nucleotide sequence of bovine copper/zinc superoxide dismutase cDNA generated by the polymerase chain reaction. PMID- 2263494 TI - An anticodon nuclease gene inserted into a hsd region encoding a type I DNA restriction system. PMID- 2263496 TI - The molecular cloning of ovine interleukin 2 gene by the polymerase chain reaction. PMID- 2263497 TI - Nucleotide and deduced amino acid sequence of cDNAs encoding two isoforms for the 17,000 dalton myosin light chain in bovine aortic smooth muscle. PMID- 2263498 TI - Nucleotide sequence and expression of the copy number control gene (cop) of the incFVII plasmid pSU233. PMID- 2263500 TI - Identification of a putative amidase gene in yeast Saccharomyces cerevisiae. PMID- 2263499 TI - Nucleotide sequence of a maize cDNA coding for a light-harvesting chlorophyll a/b binding protein of photosystem II. PMID- 2263501 TI - Nucleotide sequence of AMV-capsid protein-gene. PMID- 2263502 TI - Nucleotide sequences of the Trichoderma reesei ura3 (OMPdecase) and ura5 (OPRTase) genes. PMID- 2263503 TI - Nucleotide sequence of a cDNA encoding mouse cathepsin D. PMID- 2263504 TI - Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes. PMID- 2263505 TI - E. coli Dam activity in Hepes buffer asks for a new unit definition. PMID- 2263506 TI - G6PD Canton a common deficient variant in South East Asia caused by a 459 Arg--- Leu mutation. PMID- 2263507 TI - Rapid identification of yeast artificial chromosome clones by matrix pooling and crude lysate PCR. PMID- 2263508 TI - A unique length polymorphism in the signal peptide region of the apolipoprotein B gene in Mexican-Americans. PMID- 2263509 TI - Trinucleotide repeat polymorphism at the human intestinal fatty acid binding protein gene (FABP2). PMID- 2263511 TI - Oncology Nursing Society position paper on cancer pain. PMID- 2263512 TI - Interstitially implanted I125 for prostate cancer using transrectal ultrasound. AB - Prostate cancer is the third leading cause of death from cancer among men in the United States. Traditional treatments for prostate cancer are prostatectomy, external beam irradiation, and interstitial implantation of Iodine125 (I125) via laparotomy. These treatments are associated with significant morbidity and limitations. Based on experience with I125 interstitial implantation by transrectal ultrasound guidance for early-stage prostate cancer, it seems that this newer method of treatment has greater accuracy of placement and distribution of the isotope and has had few reported complications. The need for a surgical incision has been eliminated. Hospitalization time also has been decreased, creating the need for ambulatory and inpatient nurses to understand the importance of their respective roles in providing coordinated quality care for these patients. Nurses in these departments must have knowledge of the procedure, radiation safety, and common side effects related to the implant. PMID- 2263510 TI - New nucleotide sequence data on the EMBL file server. PMID- 2263513 TI - Recipients of bone marrow transplants: making a smooth transition to an ambulatory care setting. AB - Health care is changing rapidly due in part to Diagnostic Related Groups (DRGs), patients becoming consumer-oriented, and the Acquired Immune Deficiency Syndrome (AIDS) crisis. Patients now spend less time in acute care settings and more time recovering in an ambulatory care environment. Patients undergoing bone marrow transplants have a long, stressful, and expensive course of recovery. Patients who have had transplants are similar to other groups of patients with cancer due to the severe immunosuppression they experience. Discharge teaching is begun once granulocyte counts start to rise, and other medical problems can be monitored easily in an outpatient clinic. Being discharged from the hospital is both exciting and anxiety-provoking for patients and their families. Discharge planning requires a multidisciplinary approach. Nursing care focuses on self-care needs and prevention of infection in the face of impaired immune function. Effective discharge planning incorporates patient care needs and a focus on the patient's successful reentry into the community. PMID- 2263514 TI - Advances in antineoplastic therapy. AB - Despite advances in early diagnosis and treatment of cancer, more than a million new cases of cancer will have been diagnosed in 1990, with an estimated 10% mortality within a year of diagnosis. Thus, the search continues for new or improved antineoplastic agents with a wide spectrum of activity and decreased toxicity. The major advances in single-agent antineoplastic drug therapy include the introduction of cisplatin almost 20 years ago and of etoposide (VP-16) in the mid-1980s. However, within the past two years, analogues of existing antineoplastic agents have been purified and marketed. These drugs offer an enhanced therapeutic index when used alone or in combination with other therapies as well as decreased toxicity and, thus, may enhance patient tolerance. PMID- 2263515 TI - A trial with a new peripheral implanted vascular access device. AB - In a prospective study, a new implanted vascular access device designed for peripheral placement in the arm was evaluated. Thirty-two patients requiring long term venous access received the Port-A-Cath P.A.S. Port over a 13-month period. The access devices were used for multiple therapies including chemotherapy, antibiotics, antivirals, antifungals, and blood products. After 4,896 patient days (range 12-388), 19 complications occurred in 14 patients or 3.88/1,000 catheter days. The infection rate was 3% or 0.2/1,000 catheter days. Port pocket cellulitis was reported in 3% of patients or 0.2/1,000 catheter days. Vein phlebitis occurred at 12.5% or 0.8/1,000 catheter days. Two instances of vessel thrombosis occurred (6.2% or 0.4/1,000 catheter days). Ten incidents in six patients of inability to aspirate blood samples were noted (18.75% or 2/1,000 catheter days). No infiltrations or extravasations were reported. Nurses involved in this early trial found performance similar to the standard venous chest ports. Peripheral port placement was accepted well by patients. PMID- 2263516 TI - Young adults' reactions to the death of a parent. AB - Reactions to the death of a parent were explored in a sample of 19 adults, who were 20-39 years at the time of their parents' deaths. The majority of the young adults' parents died of cancer or heart disease in a hospital setting. Young adults' grief was often profound and accompanied by varying degrees of somatic and psychological disruption. The adults expressed a need for support and recognition of the fact that their loss was significant. Dealing with personal grief frequently was complicated by the restructuring of relationships within the family of origin. The young adults experiencing the death of a parent reported expanded perceptions of life, altered sensitivity to the passage of time, and increased importance of family ties. Nurses can assist young adults at the time of a parent's death by providing anticipatory guidance and interpersonal support. PMID- 2263517 TI - Self-identified needs of patients with cancer at home and their home caregivers: a descriptive study. AB - Increasing numbers of patients with cancer are being cared for at home by family caregivers because of the chronicity of cancer and the transition of health care from hospital to home. This study describes the needs of 15 patients with cancer at home and 15 home caregivers. Using the Objects Content Test (OCT), 505 need statements were collected from the subjects. Three hundred patient needs and 192 caregiver needs were identified. Nurse researchers and oncology experts computer Q-sorted the 505 need statements into need categories previously established by Wingate and Lackey. Patients' greatest needs were psychological, physical, and informational. Caregivers' greatest needs were psychological, informational, and those related to household duties. Qualitative data reflected that both patients and caregivers needed support from family or friends, hope, and a sense of the future. Patients indicated a need for purposeful activities. PMID- 2263518 TI - Strategies for risk management in cancer nursing. AB - In the current social and legal climate, nurses are increasingly subject to litigation charging professional negligence. A higher professional standing for nursing and a larger role in the decision-making aspects of health care have helped to effect this revolution. There are inherent risks in providing health care that are intensified by the rapid growth in medical technology and complex treatment. Claims brought against nurses have been categorized in studies, and primary causes of patient injury in the healthcare facility are also identified. Using these and other data, areas within cancer nursing that predispose to the risk of increased liability can be anticipated. Issues that are unique to the acute care, ambulatory, or homecare setting in oncology are described. Risk management is a mechanism that addresses the prevention and control of financial loss resulting from claims of negligence. Using risk management concepts, strategies are developed to help the cancer nurse recognize intrinsic dangers and reduce the potential for liability. PMID- 2263519 TI - Teaching checklist for home infusion therapy. PMID- 2263520 TI - Oncology Nursing Society position paper on cancer pain. Nursing administration. PMID- 2263521 TI - Oncology Nursing Society position paper on cancer pain. Social policy. PMID- 2263522 TI - Oncology Nursing Society position paper on cancer pain. Pediatric cancer pain. PMID- 2263523 TI - Standards for monitoring quality of analgesic treatment of acute pain and cancer pain. American Pain Society Subcommittee on Quality Assurance Standards. AB - Hospital and chronic care facilities in the United States have active "quality assurance committees" that monitor selected outcomes of care, working toward steady improvement in results. In order to harness these existing mechanisms to improve pain treatment, the American Pain Society has drafted a set of standards that embody five key elements for favorably influencing behaviors of patients and clinicians: 1) ensuring that a report of unrelieved pain raises a "red flag" that clinicians cannot ignore; 2) putting information about analgesics conveniently at hand where orders are written; 3) promising patients responsive analgesic care and urging them to communicate pain; 4) providing policies and safeguards for the use of modern analgesic technologies; and 5) monitoring the facility's success in implementing these measures. PMID- 2263524 TI - Helpful hints in caring for patients receiving biotherapy. Rigors associated with outpatient tumor necrosis factor administration. PMID- 2263525 TI - Managing side effects associated with IL-2 therapy. PMID- 2263526 TI - Cardiotoxicities of interleukin-2 (IL-2): the nursing challenge. PMID- 2263527 TI - Symptom management for patients receiving biotherapy. PMID- 2263528 TI - Neurologic toxicity management with BRMs. PMID- 2263529 TI - Alteration in body image for the patient undergoing RIL-2/LAK cell therapy. PMID- 2263531 TI - Survey of graduate programs in cancer nursing. PMID- 2263530 TI - Coping with investigational therapy. PMID- 2263532 TI - Endothelins: potent releasers of prostacyclin and EDRF. AB - The isopeptides endothelin-1 (ET-1) and endothelin-3 (ET-3) are potent vasoconstrictor substances in pithed or chemically-denervated rats. However, when injected into anesthetized rats with a high resting blood pressure, these peptides have vasodepressor actions. In addition, the pressor effects were potentiated by indomethacin indicating that release of endogenous eicosanoids modulated the pressor responses. Endothelin-1 released eicosanoids from a number of perfused isolated organ preparations. Prostacyclin and thromboxane A2 were released from perfused guinea-pig lungs, prostaglandin E2, prostacyclin and thromboxane A2 from rabbit spleen and prostacyclin and thromboxane A2 from rabbit kidneys. The eicosanoids were identified both by bioassay and by radioimmunoassay. Injection of ET-1 or ET-3 into the mesenteric artery of the rat isolated perfused mesentery preparation caused dose-related reductions in perfusion pressure. These depressor effects could be abolished by removing the endothelium with deoxycholate or by perfusing with oxyhaemoglobin, indicating that they were caused by release of EDRF. Endothelin-1 also released EDRF, identified by bioassay, from the endothelium of a perfused rabbit aorta. Endothelin-1 and ET-3 injected into anesthetized rabbits inhibited ex vivo platelet aggregation by increasing cyclic AMP, presumably through the release of prostacyclin into the circulation. Thus, endothelins release prostacyclin and EDRF both in vitro and in vivo. PMID- 2263533 TI - Secretory function of vascular endothelium and its implication in the action of vasoactive drugs. AB - Monolayer of endothelial cells is no longer considered as a plain mechanical barrier which separates blood from the rest of our body. Endothelium became recognised as a powerful generator of substances which, by interaction with blood cells or blood plasma maintain homeostasis in the circulation [2, 4, 5, 10, 26, 38, 47, 60, 65, 66]. Generation of the above substances is regulated from inside and outside of the endothelial monolayer. E.g., the generation of prostacyclin is stimulated either by a transfer of prostaglandin endoperoxides from platelets, by contact with activated leukocytes, by an increase in plasma level of bradykinin or endothelins, by a change of blood pO2, or by a damage to or distension of vascular wall. Some of the above factors are interlocked with concomitant release of prostacyclin, EDRF, endothelin I and tissue plasminogen factor [11]. Two components of the endothelial secretory system i.e. prostacyclin and EDRF, have been chosen to be reviewed here. PMID- 2263534 TI - Cardiac nociceptive reflexes: role of kinins, prostanoids and capsaicin-sensitive afferents. AB - Spinal sympathetic afferent fibres with endings in the heart are essential for signalling cardiac pain. In anesthetized, open-chest dogs, stimulation of these cardiac afferents with the algesic agents, bradykinin or capsaicin, results in reflex increases in arterial pressure and cardiac rate. The reflex responses induced by bradykinin are enhanced by concomitant application of prostaglandins of the E type or prostacyclin, and reduced by indomethacin. In contrast, the reflex effects of capsaicin are not influenced by either indomethacin or prostaglandin E1 treatment. Evidence is presented that reflexogenic effects of bradykinin involve its interaction with specific B2-receptors for kinins and that proteolysis of endogenous kininogen precursor to kinins by epicardially applied tissue kallikrein can initiate reflex cardiovascular effects. PMID- 2263535 TI - Antagonists of PAF and histamine inhibit ouabain-induced cardiac arrhythmias in sensitized guinea-pigs. AB - Platelet-activating factor (PAF) seems to be involved in different pathophysiological conditions, including cardiac arrhythmia. The arrhythmogenic potency of PAF has been shown experimentally by different methods. PAF antagonists inhibit the PAF-induced enhanced arrhythmogenicity. The present paper demonstrates that the threshold dose of ouabain-induced arrhythmia is decreased in sensitized guinea-pigs. Antagonists of PAF (BN 52021, WEB 2086, WEB 2170) and histamine antagonist clemastine can increase the threshold dose of ouabain induced arrhythmia. A combination of WEB 2170 and clemastine, each of the drug is a low dose which is without effect when applying one of them only, shows a highly significant antiarrhythmic effect in this method. The threshold dose of ouabain necessary to induce ventricular flutter was increased from 89 micrograms/kg to 129 micrograms/kg and the threshold dose of ventricular fibrillation was enhanced from 101 micrograms/kg to 137 micrograms/kg. In dependence on the pathophysiological conditions, different mediators seem to be involved in the occurrence of cardiac arrhythmia. Therapeutically influencing these mediators could be a real chance to optimise the treatment of such kind of cardiac arrhythmias. PMID- 2263536 TI - Inhibition of intravascular platelet aggregation in the rat by adrenaline. AB - Intravascular platelet aggregation to adenosine diphosphate (ADP) was measured in anesthetized rats using 111indium-labelled platelets. Acute adrenalectomy increased the aggregatory effect of ADP in vivo, whereas infusions of low concentrations of adrenaline into adrenalectomized rats suppressed ADP-induced platelet aggregation. Similar antiaggregatory effects were seen with the alpha 2 agonist B-HT 933 and the alpha 1 agonist methoxamine, but not with isoprenaline. The effect of adrenaline was inhibited by phentolamine, yohimbine, the selective alpha 2 adrenoceptor antagonist WY 26392 and by indomethacin, but not by propranolol or prazosin. Adrenaline thus inhibits ADP-induced aggregation in vivo by a mechanism that may involve stimulation of an alpha 2 adrenoreceptor and may be dependent on activation of cyclooxygenase enzyme. PMID- 2263537 TI - Abdominal fat and testes weights in diverse genetic lines of Japanese quail. AB - Six experiments were conducted to investigate abdominal fat levels in mature male and female Japanese quail following selection for 4-wk body weight and to investigate the relationship between testes development and abdominal fat accumulation. The present study utilized P-, T-, and S-line quail selected for more than 75 generations for high 4-wk body weight and also lines divergently selected (16 or more generations) for high (H-SD, H-CD) and low (L-SD, L-CD) 4-wk body weight. Adult males had from two to four times more abdominal fat than females, the reciprocal of abdominal fat patterns in chickens. These differences were observed regardless of the selection environment, direction of selection, or duration of selection. Percentage of abdominal fat was higher in high body weight lines than in low body weight lines, and correlation coefficients between body weight and abdominal fat were moderate to high (mean = .39). Correlations between abdominal fat and testes weights were positive and largest at 5 wk (r = .62). PMID- 2263538 TI - Estimates of genetic parameters in turkeys. 3. Sexual dimorphism and its implications in selection procedures. AB - Live, carcass, and skeletal data taken at 16 wk of age on 504 female and 584 male turkeys from 34 sires and 168 dams were utilized to evaluate sex differences in genetic parameter estimates. Data were transformed to common mean and variance to evaluate possible scaling effects. Genetic parameters were estimated from transformed and untransformed data. Further analyses were conducted with a model that included sire by sex and dams within sire by sex interactions, and the variance estimates were used to calculate genetic correlations between the sexes and genetic regression parameters. Heritability estimates from transformed and untransformed data were similar, indicating that sex differences were present in the genetic parameters, but scaling effects were not an important factor. Genetic correlation estimates from paternal (PHS) and maternal (MHS) half-sib estimates were close to unity for BW (1.14, PHS; 1.09, MHS), shank width (.99, PHS; .93, MHS), breast muscle weight (1.23, PHS; 1.04, MHS), and shank length (1.09, PHS; .97, MHS). However, abdominal fat (.79, PHS; .59 MHS), total drumstick muscle weight (.75, PHS; 1.14, MHS), rough cleaned shank weight (.78, PHS; not estimatable, MHS), and shank bone density (1.00, PHS; .53, MHS) estimates were somewhat lower. The estimates suggest that the measurement of these latter "traits" at the same age in the two sexes may, in fact, be measuring different genetic effects and that selection procedures in turkeys need to take these correlations into account in order to make optimum progress. The genetic regression parameters indicated that more intense selection in the sex that has the smaller genetic variation could be practiced to make greater gains in the opposite sex. PMID- 2263539 TI - Cage- and floor-rearing effects on subsequent behavior of white leghorn layers in multiple-bird cages. PMID- 2263540 TI - Effect of four levels of added fat on broiler breeder performance. AB - Broiler breeders were fed corn-soybean diets and reared under 8 h of incandescent light. Birds were photostimulated with a mixture of incandescent light and daylight at 20 wk of age. Corn-soybean breeder diets with 0, 2, 4, and 6% added poultry fat were fed from 24 to 64 wk of age. Daily feed allocations were adjusted to provide comparable calculated protein intake at peak egg production; calculated ME intake was 413, 437, 461, and 484 kcal per bird per day for the 0, 2, 4, and 6% added fat diets, respectively. Feed was gradually reduced such that ME intake reached 400, 415, 429, and 422 kcal ME per bird per day from 57 to 64 wk of age for the respective diets. When compared with 0%, all levels of added fat significantly increased egg production and feed conversion. Fertility was increased significantly with the 4% added fat when compared with fertility at 2%; fertility with 0 or 6% added fat was intermediate. Female body weight increased in a dose-related manner in response to added fat. Chicks per hen was maximized at 4% added fat. Taken together, the data are interpreted to mean that 4% added fat is near the optimum for broiler breeders. PMID- 2263541 TI - The effect of dietary tryptophan on aggressive behavior in developing and mature broiler breeder males. AB - Broiler breeders display high levels of aggressive activity as a result of feed restriction. The objective of this study was to determine if aggressive activity in developing and mature broiler breeder males is influenced by increased dietary L-tryptophan (Trp). Broiler breeder males were raised using a skip-a-day feed restriction regimen. In Experiment 1, three levels of dietary Trp, .19 (control), .75, and 1.5%, were fed from the start of feed restriction at 4 wk of age and throughout development. All occurrences of aggressive behavior were recorded during three 20-min observation sessions per week on mornings on which feed was not delivered through Week 20. The Trp significantly decreased (P less than .05) aggressive pecking in birds fed supplemental Trp as compared to controls. No differences in threatening behavior were found. In the second part of Experiment 1, the effect of continued Trp supplementation on mature flocks of male broiler breeders and time-of-day effects on aggression were investigated. A depressing effect of supplemental Trp on pecking and threatening was observed. Maximum aggressive activity in all treatment groups occurred on mornings when feed was delivered. In Experiment 2, four levels of Trp, .19 (control), .38, .75, and 1.5%, were fed to developing birds as in Experiment 1. Birds fed supplemental Trp pecked less (P less than .05) than controls and .38% Trp was as effective in decreasing pecking as was 1.5%. It was concluded that increased levels of dietary Trp decrease aggression in both developing and mature, socially stable flocks of broiler breeder males. PMID- 2263542 TI - Prevention of coccidiosis in the chukar partridge (Alectoris chukar) by medication with sulfadimethoxine and ormetoprim (Rofenaid). AB - Rofenaid (a 5:3 mixture of sulfadimethoxine and ormetoprim) was effective in preventing coccidiosis of chukar partridges. Levels of .0100 or .0125% sulfadimethoxine, with the corresponding level of ormetoprim in the ration, gave the best results. These levels markedly reduced mortality in severe infections (over 75% mortality in unmedicated chukars) and eliminated mortality in medicated groups when infections produced 52% mortality or less in unmedicated controls. In the latter infections, Rofenaid also protected against the depression in weight gain seen 6 days postinoculation in unmedicated chukars. Studies in uninoculated chukars showed that Rofenaid has a wide safety margin and did not produce adverse effects even at levels of .0300% sulfadimethoxine. Rofenaid should, therefore, be an effective medication for the prevention of coccidiosis in chukars in the field. Data from the present studies are being submitted to the IR-4 Program of the Food and Drug Administration for consideration of approval for the use of Rofenaid in chukar partridges. PMID- 2263543 TI - The effect of light and environmental temperature on broiler digestive tract contents after feed withdrawal. AB - Contamination from the digestive tract is a persistent problem in broiler processing. Two experiments were conducted to determine the effects of lighting and environmental temperature on quantity of crop, gizzard, and small intestine contents during feed withdrawal. Broilers were on litter with a feeding regimen of 1.5 h on feed and 4.5 h off feed for 1 or 2 days. The withdrawal period began at the end of a 1.5-h feeding period. In the first experiment, broilers were cooped or left on the floor with and without lights. Crop contents of lighted broilers at 21 C were reduced 2 h after feed withdrawal for broilers on litter and in coops. In another experiment, broilers on litter were maintained at 18 and 27 C in light or in darkness. Lighting reduced crop contents 4 h after feed withdrawal but increased the contents of the small intestine 2 h after feed withdrawal at both temperatures. These results indicate that crop clearance is improved by lighting both before and after cooping. PMID- 2263544 TI - Comparative effects of dietary tannins in ducks, chicks, and rats. AB - Studies were conducted to compare the effects of feeding high-tannin sorghum (HTS)- and low-tannin sorghum (LTS)-based diets suboptimal in protein to ducks, chicks, and rats. In the first series of experiments, Savanna (HTS) depressed both growth and feed efficiency of chicks and rats when compared with animals fed RS-610 (LTS). In contrast, ducks fed Savanna-based diets exhibited greater weight gains, but poorer feed efficiency values than birds fed RS-610. In a second series of experiments, Pioneer 8333 (LTS) and DeKalb BR-64 (HTS) sorghum-soybean meal diets were fed to chicks, ducks, and rats. As compared with animals fed 8333, BR-64 depressed both growth and feed efficiency of chicks and rats, but did not significantly affect either parameter in ducks. The lack of effect of HTS on duck growth may have been due to the formation of tannin-protein complexes upon exposure of the ground grain to water. This theory was based on the following observations: 1) ducks consumed water immediately after eating to facilitate swallowing the dry-mash diet; 2) a large amount of feed was deposited on the bottom of each water trough and subsequently consumed; and 3) ground HTS, which had been soaked for 4 h, had virtually no assayable tannin after drying. However, despite the marked reduction in assayable tannin content of treated HTS versus HTS that was dried only, the former material still depressed growth and feed conversion of rats. Thus, the lack of a growth-depressing effect of sorghum tannins in ducks fed dry-mash diets is both unique and unexplained. PMID- 2263545 TI - Effect of feeding cholesterol to laying hens and chicks on cholesterol metabolism in pre- and posthatch chicks. AB - Single Comb White Leghorn laying hens that were 60 wk of age were fed wheat and soybean meal diets containing either 0 or 1% cholesterol. Birds were artificially inseminated, and fertilized eggs were collected for incubation after a plateau of egg cholesterol content was reached. Posthatch chicks were raised with starter diets containing either 0 or .5% cholesterol. Samples of developing embryos and posthatch chicks at various stages were prepared for cholesterol analysis. As compared with controls, cholesterol content of eggs from hens fed 1.0% cholesterol diet was increased by approximately 70%. Embryos from the cholesterol loaded eggs had significantly higher (P less than .05) cholesterol content. The plasma total cholesterol (TC) level in chicks from cholesterol-loaded eggs, when compared with TC in control eggs, was significantly higher at hatching but decreased to the same level by 2 wk after hatching. Cholesterol feeding to newly hatched chicks elevated plasma TC and high-density lipoprotein cholesterol levels. The TC contents of liver and heart, but not skeletal muscle, were significantly higher in chicks fed the .5% cholesterol starter diet than those fed the cholesterol-free diet. These results show that cholesterol metabolism in developing embryos and posthatch chicks is influenced by cholesterol in both maternal and chick diets. PMID- 2263546 TI - Optimal dietary level of 1 alpha,25-dihydroxycholecalciferol for eggshell quality in laying hens. AB - The optimal dietary level of 1 alpha,25-dihydroxycholecalciferol [1,25-(OH)2D3] for eggshell quality was established. White Leghorn hens, 59 wk of age, were fed one of eight diets that contained the same basal ingredients, including 3.1% calcium, but different levels (microgram/kg) or forms of calciferol supplements: no calciferol supplement of any form (56 hens); 27.5 (control) or 55.0 micrograms of cholecalciferol (56 hens each); 3, 5, or 7 micrograms of 1,25-(OH)2D3 (28 hens each); 5 micrograms of 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] with 28 hens; 5 micrograms each of 1,25-(OH)2D3 and 24,25-(OH)2D3 (28 hens). All groups were fed the control diet prior to the 21-wk treatment. The group fed 5 micrograms 1,25-(OH)2D3/kg diet ranked first in specific gravity (SG), e.g., 1.081 versus 1.077 for the control group at Week 21 (P less than .05). The group fed 7 micrograms 1,25-(OH)2D3/kg consumed 30% less feed and laid 20% fewer eggs than the control, but shell quality was not affected. The groups receiving no calciferol supplement or receiving only 24,25-(OH)2D3 laid eggs with significantly lower SG than the control after 2 wk of treatment (1.072 or less versus 1.082 at Week 2). The rest of the treatment groups mentioned were comparable to the control in eggshell quality and egg production. Groups fed the combination of 1,25-(OH)2D3 and 24,25-(OH)2D3 per kilogram of feed, or 1,25 (OH)2D3 alone at 5 micrograms/kg, had significantly higher tibial weights relative to the control group. All groups receiving the diets without cholecalciferol supplementation had markedly reduced hatchability. It was concluded that the optimal dietary level of 1,25-(OH)2D3 for improving eggshell quality without affecting egg production was approximately 5 micrograms/kg and the toxic level was 7 micrograms/kg. PMID- 2263547 TI - Effects of egg weight, glucose administration at hatch, and delayed access to feed and water on the poult at 2 weeks of age. AB - Eggs from a 42-wk-old small-type turkey breeder flock were weighed and divided into heavy, medium, and light categories relative to the population average. Poults from each category were sexed, then given .5 mL of 50% glucose in saline by either crop intubation (CI) or subcutaneous injection at the neck (SC). Controls did not receive glucose. One-half of the birds from each treatment were immediately given access to feed and water in pens of brooder batteries; the remainder were held 3 days in transportation boxes before placement in other pens of the same batteries. Poult weight at hatching and 3 days later paralleled egg weight. Improvement in 3 day BW occurred after glucose administration and was greater by SC than CI, but these advantages were only apparent when feed and water had been accessible during the interim. Egg weight effects on BW and gain persisted to 2 wk of age, as did the depression from delayed nutrient access; however, the advantage from glucose with poults having early access to nutrition disappeared. Alterations in the proximate compositions of livers and carcasses among treatments were small. Total mortality increased with egg weight when poults received feed and water early after hatching, while the converse occurred when delayed. Deaths were not altered by either glucose or fasting (P greater than .05). PMID- 2263549 TI - The effect of restrictive and compensatory growth on the incidence of leg abnormalities and performance of commercial male turkeys. AB - To determine if excessive body weight and dietary protein and amino acid intake contribute to the incidence of leg deformities, the growth of male turkeys was restricted from 6 to 12 wk and from 6 to 20 wk of age by feeding diets for ad libitum intake that were low in dietary protein and amino acids (74% of controls). For those turkeys whose growth was restricted from 6 to 12 wk of age, a return to control diets (low compensatory plane) or to 20% above control diets (high compensatory plane) with respect to protein and amino acids resulted in live body weights comparable with controls at 20 wk of age. Feed to gain ratios (0 to 20 wk) were comparable between compensated and control birds, and protein efficiency was improved for birds fed the low compensatory plane diets. Restricting growth significantly lowered the incidence of leg abnormalities at 12 wk of age (P less than .05), as compared with controls, but by 20 wk, only birds fed the low compensatory plane diet showed a lowered incidence (P less than .06). These results on leg abnormalities (mainly valgus-varus deformities) suggest that rapid weight gains or dietary protein and amino acid intake may contribute to the leg weakness syndrome but is certainly not the only factor involved. PMID- 2263548 TI - Nutritional implications and metabolizable energy value of D-xylose and L arabinose in chicks. AB - An experiment was conducted to examine the effects of graded levels (2.5, 5.0, 7.5, 10.0, and 15.0%) of dietary D-xylose or L-arabinose on chick performance. As reference, D-glucose was included in the experiment. A second experiment was performed to determine the AMEn of D-xylose and L-arabinose. Results of Experiment 1 showed a significant linear decrease (P less than .05) in weight gain and efficiency of feed utilization when the dietary level of either D-xylose or L-arabinose was increased. The same was true for daily feed intake of the D xylose treatments. Water intake was linearly (P less than .05) increased as dietary level of both pentose sugars increased, and, as a result, dry matter content of the droppings decreased. Results of Experiment 2 showed that the AMEn value of either pentose sugar was dose related. The AMEn values for D-xylose at 5 and 10% dietary inclusion were 2,660 and 2,020 kcal/kg, respectively. Those for L arabinose at these inclusion levels were 2,300 and 1,360 kcal/kg, respectively. Feeding equal dietary levels of either pentose sugar resulted in higher concentrations of xylose than of arabinose in blood plasma. Concentration of glucose in blood was not affected by feeding either D-xylose or L-arabinose. Cecal length and weight were markedly increased by feeding L-arabinose and intermediately by D-xylose. PMID- 2263550 TI - The effect of compensatory growth on carcass characteristics of male turkeys. AB - Male turkeys were fed for ad libitum intake dietary levels of protein and amino acids at 74% of controls from 6 to 12 wk of age. The treatment in which birds were returned to control rations from 12 to 20 wk of age was designated as the low compensatory plane dietary regimen. Turkeys given diets with protein and amino acids at levels 20% above those in control diets from 13 to 20 wk of age were referred to as the high compensatory plane dietary regimen. By 20 wk of age, realimentation had successfully resulted in live body weights comparable with those of controls, but carcass weights were significantly lower in birds fed the low and high compensatory plane diets. Percentage yield of drums, wings, shell, as well as skin and fat did not differ among dietary treatments. Lowered protein and amino acid consumption from 6 to 12 wk of age caused lighter breast and breast muscle weights at 20 wk of age. The percentage yield of breast and breast muscle declined, and thigh and thigh muscle increased for the birds fed the low compensatory plane diet when compared with the controls. The birds fed the low compensatory plane diet were placing a greater proportion of their weight gains during realimentation on thigh muscle rather than breast muscle deposition. Compensatory growth did not affect the absolute length or width of the tarsometatarsus or testes weights at 20 wk of age. PMID- 2263551 TI - Effect of feed restriction during the rearing period on the growth rate and carcass composition of turkey breeder hens. AB - An experiment with Nicholas parent-stock turkey breeder hens was designed to determine the effect of feed restriction on body weight and carcass composition. The following six feeding programs were compared using four replicate pens of 15 or 16 poults each: ad libitum intake of conventional corn and soybean diets (Ad), skip 1 day per week (S1), skip 2 days per week (S2), 95% of ad libitum (95%), 90% of ad libitum (90%), and 85% of ad libitum (85%). At 29 weeks of age, Ad birds were heavier than restricted birds (P less than .05); there were no differences among S1, S2, and 95% or between 90% and 85% treatments. The 95%, 90%, and 85% hens did not have as much carcass fat as did Ad hens (P less than .05); there were no differences among Ad, S1, and S2 treatments. The results of the present study show that feed restriction during the rearing period reduces the growth rate of turkey breeder hens. Quantitative feed restriction (95%, 90%, and 85%) appears to be the most effective method to reduce carcass fat content. PMID- 2263553 TI - Analysis of poultry fertility data. AB - Single Comb White Leghorn (SCWL) hens were inseminated intravaginally with spermatozoa from either SCWL or subfertile Delaware roosters in three replicate fertility trials. Overall fertility was analyzed with a log odds model following logit transformation. Duration of fertility was analyzed by iterative least squares. Hens inseminated with spermatozoa from SCWL males laid a higher proportion of fertilized eggs over a longer interval than those inseminated with spermatozoa from affected Delawares. Log-odds and logistic models may have advantages over the more traditional methods of evaluation. This is particularly true in regard to the distribution and normalization of error variances via the logit transformation and removal of nonadditivity via logistic regression. PMID- 2263552 TI - Contraceptive action of glycerol on chicken spermatozoa in oviducal organ-slice cultures. AB - Chicken spermatozoa in diluent with and without glycerol were evaluated after coculture with oviducal tissues. The motility of glycerolized (G) spermatozoa was lower in the cultures of vaginal tissue than in uterine tissue. The percentage of dead, G spermatozoa increased in cultures of the vagina and uterus but not in infundibulum cultures. Glycerol significantly increased the percentage of dead spermatozoa in both vaginal and uterovaginal cultures when compared to nonglycerolized spermatozoa in the same cultures. The percentage of dead G spermatozoa was higher for semen in vaginal culture than in uterovaginal culture. Uterovaginal tissue appeared to protect spermatozoa from some of the detrimental effects of glycerol. Incubation time had a significant detrimental effect on motility and percentages of dead and abnormal spermatozoa regardless of semen or tissue treatment. PMID- 2263554 TI - Energy requirement of feed-restricted broiler breeder pullets. AB - The energy requirements for growth and maintenance of broiler pullets were studied during a 17-wk growing period. Four flocks of commercial broiler replacement pullets, housed in conventional poultry houses, received a restricted amount of feed on 4 or 5 days a week, and pullet growth was recorded. The energy needs for maintenance and body weight gain under a feed restriction regimen was calculated using a model based on metabolic body weight and weight gain described by Hurwitz and coworkers. Average daily body weight gain for the entire experimental period was 13.7 g; the daily energy intake increased with age from 114 kcal/day at 3 wk of age to approximately 270 kcal/day at 20 wk. The estimated daily metabolizable energy requirement for maintenance was 1.57 kcal/g of body weight67 and for growth, .71 kcal/g of body weight. It was concluded that the energy requirement for birds under a feed restriction regimen is considerably lower than those under ad libitum feeding. PMID- 2263555 TI - Altered renal function in broilers during aflatoxicosis. AB - Experiments were conducted to determine the effects of aflatoxicosis on acid-base balance, urine flow rate (V), glomerular filtration rate (GFR), clearance of para aminohippuric acid (CPAH), plasma osmolality, and the renal handling of Na, K, Ca, and P. Three-week-old broilers were gavaged with aflatoxin at a dose of 2 mg/kg of BW per day for 10 consecutive days. Control birds received an equal volume of corn oil, the aflatoxin carrier vehicle. On the eleventh day, the birds were anesthetized and prepared for renal function analysis. A solution containing inulin, para-aminohippuric acid, and mannitol was infused at a low infusion rate (.1 mL/kg of BW per min) and a high infusion rate (.4 mL/kg of BW per min) to determine if aflatoxin affects the renal response to an acute volume load. Aflatoxicosis decreased the fractional excretion of phosphorous (FEP) and plasma Ca concentration but did not significantly alter any other renal function or acid base variables. The decrease in FEP and plasma Ca may be a direct result of renal tubular damage, decreased Ca absorption from the gut, or a result of altered circulating levels of parathyroid hormone (PTH), and possibly decreased renal sensitivity to PTH. PMID- 2263556 TI - Comparison of microscopic and laser diffraction methods for measuring sarcomere lengths of contracted muscle fibers of chicken pectoralis major muscle. AB - The objective of the present study was to compare the effectiveness of a microscopy method with a laser diffraction method for measuring sarcomere lengths of chicken pectoralis major (p. major) muscle fibers exhibiting various contraction states. Chicken p. major muscles were excised from the animals at death. Samples of each muscle were treated with pH-buffered (5.0 and 7.5) isoionic CaCl2, KCl, or ethylene glycol bis-(b-aminoethyl ether) N,N,N',N' tetraacetic acid (EGTA) solutions in order to produce variability in the degree of fiber contraction. Sarcomere lengths (SL) of the fibers were observed using light microscopy and a laser diffraction method. The methods gave comparable results for sarcomere lengths greater than 1.6 microns. However, for SL less than 1.6 microns, sarcomere contraction was not accurately assessed by the laser diffraction method. PMID- 2263557 TI - Energy supplementation of laying hen feed and drinking water. AB - Duplicate experiments were conducted with White Leghorn pullets (29 and 31 wk old) to determine the influence of sucrose additions to feed or drinking water upon performance and average daily energy intake. Treatments consisted either of 3.06 or 4.58% sucrose in drinking water or of 4.76% sucrose in the feed compared with a control diet containing 2,657 kcal ME/kg. In each experiment, six replicate pens of 5 individually caged hens received feed or water treatments ad libitum for 42 days. Egg production and body weight change were not affected in either experiment by sucrose addition. Feed intake was significantly reduced in association with either level of sucrose in the water. In Experiment 1, egg weights from hens receiving sucrose water were significantly below those of controls, probably because of lowered feed intake. Total energy consumed per gram of body weight was significantly higher in both studies for birds receiving the sucrose water. PMID- 2263558 TI - Fifty percent colonization dose for Salmonella typhimurium administered orally and intracloacally to young broiler chicks. AB - One and 3-day-old chicks were challenged with varying levels of Salmonella typhimurium by gavage or intracloacal administration. Chicks were killed 5 days postchallenge, and ceca were analyzed for the presence of S. typhimurium. About 100-fold fewer S. typhimurium cells were required to colonize young chicks by the intracloacal route than by gavage. It was hypothesized that the low pH of the upper gastrointestinal tract contributes to the higher levels of Salmonella required to colonize young chicks via the oral route. The pH measurements in the gizzard of freshly killed chicks were variable, but most were low enough to be bactericidal. Presence of salmonellae in the hatchery environment and the low level of cells (2 cfu) required to colonize young chicks via cloacal challenge suggest that day-of-hatch chicks may be at a high colonization risk from salmonellae in the hatchery. PMID- 2263559 TI - Estimation of nitrogen-corrected true metabolizable energy of two different barley samples with and without enzyme supplementation over different excreta collection times. AB - The TMEn values of two barley samples and a corn sample with and without enzyme addition were determined in an experiment conducted over two consecutive weekly periods. Adult roosters were not influenced by the high beta-glucan content of Scout barley, which had a higher energy value (3.70 kcal/g DM) than the Bedford barley (3.44 kcal/g DM). Overall the energy value of the grain increased 3% due to enzyme supplementation. The 48-h excreta collection time was considered to be adequate for TMEn determination. PMID- 2263560 TI - Effect of biosynthetic chicken growth hormone on egg production in White Leghorn hens. AB - Two studies were conducted to determine if injection of recombinant chicken growth hormone (cGH) influences egg production parameters in older laying hens. In both experiments, hens were subjected to consecutive 3-wk periods consisting of 1) a preinjection period, 2) an injection period, and 3) a postinjection period. During the 3-wk injection period, hens were injected once daily with either 5, 50 or 500 micrograms/kg BW of cGH or physiological saline (vehicle) alone (control group). In both experiments, injection of cGH did not affect (P greater than .05) percentage of daily egg production per hen, Haugh units, or BW during the injection period compared with preinjection hens. In Experiment 1, but not Experiment 2, control hens had reduced shell thickness and feed consumption during the injection and postinjection periods when compared with the preinjection controls. These reductions were not observed in hens receiving injections of cGH (all doses). PMID- 2263562 TI - [Multiple primary malignant tumors in an unselected autopsy sample]. PMID- 2263561 TI - The effect of 1 alpha,25-dihydroxyvitamin D3 added to a layer diet containing adequate amounts of vitamin D3 on the performance of layers. AB - The effect of adding 1 alpha,25-dihydroxyvitamin D3 (calcitriol) to a well balanced, commercial layer diet containing 1,900 IU vitamin D3/kg on eggshell quality and laying performance of 56-wk-old White Leghorn hens was investigated. After 8 wk of treatment, calcitriol at 1.5 micrograms/kg diet had no discernible effect on egg weight, egg deformation, percentage shell, shell thickness, feed consumption, and egg production. At 3.0 and 4.5 micrograms/kg, feed consumption, feed production, and egg weight were significantly reduced, whereas egg deformation, percentage shell, and shell thickness were not affected. The results show that calcitriol added to a diet already adequately supplemented with vitamin D3 does not improve eggshell quality and may impair laying performance. PMID- 2263563 TI - [Morphology of vacuolar changes in the spinal cord of AIDS patients (vacuolar myelopathy)]. PMID- 2263564 TI - [Histopathology of malignant atrophic papulosis (Kohlmeier-Degos disease)]. PMID- 2263565 TI - [Morphologic characteristics and specifics of osteoid osteoma]. PMID- 2263566 TI - [Serous-papillary carcinoma of the uterus]. PMID- 2263567 TI - [Hepatic capillariasis. Morphology and differential diagnosis]. PMID- 2263568 TI - [Chondroosteoid breast tumor with multi-nucleated giant cells. Case report and review of the literature]. PMID- 2263569 TI - [Gustav Ricker (1870-1948)--his life and work]. PMID- 2263570 TI - [Breast saving therapy of breast cancer--indications and consequences. Results of a multidisciplinary consensus conference in Berlin, November 2-3, 1989]. PMID- 2263571 TI - Manipulation of fecal pH by dietary means. AB - Epidemiological and animal studies suggest that colonic fermentation and fecal pH may be risk factors for colorectal cancer. To modify these factors, we sought to develop a simple instrument for use in intervention studies. Three 14-day studies with 32, 40, and 30 healthy volunteers maintained on their regular diet were carried out to evaluate the effect of various food supplements on fecal pH. The interventions tested included supplementary lactulose, Metamucil, oat bran, wheat bran, or no supplement. The results showed that it is possible to provide a simple intervention to reduce fecal pH by 0.4 unit with oat bran administered at 75-100 g/day over a 14-day period, using a wheat combination, equivalent in macronutrients and fiber, as a control. PMID- 2263572 TI - Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. AB - Epidemiologic and laboratory evidence suggests that vitamin D may play a role in reducing breast cancer risk. Lack of exposure to ultraviolet sunlight can increase the prevalence of vitamin D deficiency. This deficiency may place some populations at higher risk for breast cancer. The association between total average annual sunlight energy striking the ground and age-adjusted breast cancer mortality rates in 87 regions of the United States was evaluated. Annual age adjusted mortality rates for breast cancer varied over a 1.8-fold range, from 17 19 per 100,000 in the South and Southwest United States to 33 per 100,000 in the Northeast; the overall U.S. rate was 27.3 per 100,000. Risk of fatal breast cancer in the major urban areas of the United States was inversely proportional to intensity of local sunlight (r = -0.80, P = 0.0001); multiple regression with stratospheric ozone measurements, r = -0.82, P = 0.0001). Vitamin D from sunlight exposure may be associated with low risk for fatal breast cancer, and differences in ultraviolet light reaching the United States population may account for the striking regional differences in breast cancer mortality. The ecological nature of this study is emphasized, and the possibility that an indirect association with dietary and socioeconomic factors could explain these findings is discussed. PMID- 2263573 TI - Do oral contraceptives increase blood pressure and serum total cholesterol in young women? AB - The effects of the use of oral contraceptives on serum lipids and blood pressure were studied among young women who participated in a longitudinal survey of risk factors for coronary heart disease (CHD) in the Netherlands. Fifty-three participants, ages 14 to 24 years, initiated oral contraceptive use during follow up to the primary study on CHD. They continued oral contraceptive use for at least 2 subsequent years. From 53 age-matched control subjects, who did not use oral contraceptives, data were obtained for the same follow-up period. Women using oral contraceptives showed a significantly greater rise in serum total cholesterol levels than did the reference subjects (14 mg/100 ml/2 year vs 4 mg/100 ml/2 year; 95% confidence interval of the difference was 0.1 to 19.6). The increase in systolic blood pressure (4.7 mm Hg/2 year vs 2.1 mm Hg/2 year; 95% confidence interval of the difference was -1.8 to 6.9) did not differ between the groups. These findings suggest that oral contraceptive use may be associated with an enhanced rise in total cholesterol during adolescence. PMID- 2263574 TI - Improving follow-up after an abnormal Pap smear: a randomized controlled trial. AB - Less than 60% of women diagnosed with cervical abnormalities on Pap smears return for proper surveillance and timely treatment. Previous tactics used to motivate these women to return have mainly relied on costly intensive recall efforts. Using a framework based on psychological value expectancy theory, a pamphlet was designed to motivate women with abnormal Pap smears to return for a repeat Pap smear. The effect of this pamphlet was tested in a randomized controlled trial. A total of 161 women with abnormal Pap smears were randomized and received either the pamphlet plus a notification letter or the letter only. The compliance rate was 64.2% in the intervention group and 51.3% in the comparison group (P = 0.10; two-tailed). In addition, subgroups of women who do not practice health-related behaviors were identified as groups where more intensive interventions may be needed. These results have implications for future strategies used to recall women with abnormal Pap smears. PMID- 2263575 TI - Tracking of health and risk indicators of cardiovascular diseases from teenager to adult: Amsterdam Growth and Health Study. AB - Cardiovascular disease is recognized as a serious public health problem. Because the underlying pathological processes start shortly after birth, tracking of recognized cardiovascular disease indicators during childhood and adolescence can help in developing preventive pediatric strategies. A prospective follow-up of both genetic and behavioral lifestyle parameters (serum cholesterol, blood pressure, percentage body fat, maximal oxygen uptake (VO2max), smoking, physical inactivity, and type A behavior) was designed. In the Amsterdam Growth and Health Study a population of 93 males and 107 females was measured annually from 1977 to 1980 and a fifth measurement was made in 1985. In that way longitudinal data covering a period of 8 years was collected for a group of adolescents/adults between 13 and 21 years of age. Analyses of these parameters provided the following results: The stability over the 9 years of tracking cardiovascular disease indicators, measured as the interperiod correlations, is fairly high. It varies from 0.4 to 0.8 in percentage body fat, cholesterol, and VO2max. Blood pressure values are low (between 0.3 and 0.4). The probability of 13-year-olds having relatively high values of cardiovascular disease indicators on the basis of a quartile distribution with that at age 21 indicated a moderate to high predictive value. According to the literature, the levels of subjects that are continuously relatively high over the years are more in the direction of optimal health than risk values. The exception is for percentage body fat. Interrelation of the seven cardiovascular disease indicators in constantly relatively high-risk and relatively low-risk groups during the teenage period, measured during young adulthood (21.5 years), appeared to be weak: only males and females with a high percentage body fat and a low VO2max showed significantly high total cholesterol, low high-density lipoprotein cholesterol, and high total cholesterol/high-density lipoprotein cholesterol levels. From the three environmental cardiovascular disease indicators (smoking, physical activity, and type A/B behavior) measured in 1985, only physical activity was significantly correlated among males and females with high-density lipoprotein cholesterol, percentage body fat, and VO2max. It can be concluded that measurement of percentage body fat in the early teenage period seems to be the most important cardiovascular disease indicator in predicting risk levels in the young adult. The amount of physical activity measured at young adult age is the only behavioral parameter to show a significant interrelation with other cardiovascular disease risk indicators.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2263576 TI - Behavioral coronary risk indicators and apolipoproteins A-I and B in young Finnish children: cross-sectional and predictive associations. AB - The association between behavioral and somatic coronary risk indicators was studied in 3-, and 6-, and 9-year-old children (n = 668). The behavioral risk indicators used were the Type A behavior pattern, hyperactivity, social maladjustment, and life dissatisfactions of the mother. The somatic risk indicators adopted were serum concentrations of apolipoproteins B and A-I. The results might indicate that behavioral and somatic coronary risk indicators are not independent, but could share a common basis, or pathways that are related to the pathogenesis of CHD. In addition, a sex-related difference was discovered: variables associated with the high somatic risk level among girls were hyperactivity, social maladjustment, and impatience, and among boys the variables were the mother's dissatisfaction with herself as a mother, leadership, and a tendency for competitiveness-aggression. PMID- 2263577 TI - Use of smokeless tobacco among conscripts: a cross-sectional study of Norwegian army conscripts. AB - In a cross-sectional study of 2,112 Norwegian army conscripts ages 18 to 25 years, 10% reported daily use of wet snuff, while 23% were occasional users. Nearly half of the snuff users had started or increased their consumption during the military service. Cigarette smoking, alcohol consumption, and having a best friend using snuff were positively correlated with starting to use snuff. Daily use was associated with high physical activity. Use of snuff did not vary significantly with length of education when adjusting for other variables. Nearly all subjects believed prolonged snuff use to be a hazard to health. Forty percent of the snuff users believed they would give up snuff after the military service. Giving up during the service was statistically associated with having a steady relationship with a girlfriend and with length of time served. The relatively high percentage of occasional users and the high rate of stopping and starting reflect the novelty of snuff use among Norwegian youth. The widespread intention to give up seems to indicate that a large proportion of snuff users have ambivalent attitudes toward their own behavior. Therefore, future intervention measures in the armed forces could have a substantial impact on young males' use of smokeless tobacco. PMID- 2263578 TI - Predictors of smoking behavior change 6 and 18 months after individual counseling during periodic health examinations. AB - Predictors of smoking behavior change were examined in a randomized controlled trial of individualized smoking cessation counseling delivered by a smoking cessation counselor during periodic health examination. Self-reports of not smoking at 6 and 18 months and attempts to quit were greater, but not significantly so, in the intervention group compared with the usual care group. There was no difference between the intervention group and the usual care group in reported continuous abstinence. Multivariate analysis showed that longer periods of abstinence in the past and having smoking identified as the main problem were important predictors of subsequent quitting. Having fewer other smokers in the household, stronger intentions to stop smoking in the next month, and being in the intervention group were also significant predictors of abstinence at 6 months, but not at 18 months. Those who had tried to quit by 6 months and 18 months were more likely to be in the intervention group, to have greater motivation to stop smoking, and to have more problems of daily living. Supplementing physician's advice with individualized smoking cessation counseling during health maintenance examinations was associated with a greater short-term quit rate and more quit attempts over 18 months than physician advice alone, but did not influence continuous abstinence from cigarettes over this time. PMID- 2263579 TI - Use of medical resources--overview. PMID- 2263580 TI - The regulation of medical devices. PMID- 2263581 TI - Public health regulation and control of population exposures to ionizing radiation. PMID- 2263582 TI - The use and abuse of therapeutic modalities in breast cancer. PMID- 2263583 TI - Scientific basis for resource allocation. PMID- 2263584 TI - AIDS: politics and science. PMID- 2263585 TI - [Controlled study of the effect of sports training on cardiopulmonary functions in asthmatic children and adolescents]. AB - The influence of physical training on the cardiopulmonary system and on lung function of asthmatic children was determined in a controlled study. The children were all indoor patients of the Hochgebirgsklinik Davos, Switzerland. 36 children at the age of 10 to 16 years entered the study. They were placed into either a "free running group", a "swimming group" or a "control group." The children of the training groups underwent a training of at least 10 units of 30 minutes each in 3 weeks. The control group did not participate in any regular physical training. Heart rate was measured before and after a bicycle ergometer exercise of 5 minutes at 2.5 watts/kg body weight. This was repeated at the end of the study. In the "free running group" a significant decrease of the heart rate at rest (p less than 0.05) and at the end of bicycle ergometer exercise (p less than 0.01) could be seen. In the "swimming group" the decrease of the latter was significant (p less than 0.05). In both groups an increase in work tolerance could be demonstrated, but not in the "control group." In all three groups an improvement of lung function (IVC, FEV1) was found, but it was not significant in any of the groups. The small improvement might be due to a reduction in allergen exposure and better medical treatment. The study confirms the possibility of physical training of children with asthma even if exercise-induced asthmatic signs and symptoms are present. PMID- 2263586 TI - [Congenital lung hypoplasia in adulthood]. AB - This is a report on a largely asymptomatic patient with a unilaterally non functional lung. The differential diagnosis between an acquired, "destroyed" lung and congenital hypoplasia of the lung with secondary inflammatory changes proves difficult. The various imaging procedures that are available, used in conjunction with the histological findings, permit a classification. PMID- 2263587 TI - Aging, Alzheimer disease, and amyloid. PMID- 2263588 TI - Fine needle aspiration biopsy of extramedullary plasma cell tumors. AB - Fourteen fine needle aspiration (FNA) biopsies of extramedullary plasma cell tumors (PCT) from 11 patients were reviewed and correlated with histology in eight patients. This series comprised seven men and four women ranging in age from 46 to 83 yr (median 69 yr). Discrete masses were located in lymph nodes (three patients), pleura (one patient), soft tissues of the neck (two patients), thorax (six patients), axilla (one patient), and inguinal region (one patient). A spectrum of cytologic findings was demonstrated which led to the clinical confirmation of myeloma in four of 11 patients and of solitary plasmacytoma in two of 11 patients. In addition, FNA biopsies confirmed the presence of extramedullary disease in four of 11 patients with previously diagnosed myeloma. In another patient with a poorly differentiated plasma cell neoplasm, excisional biopsy was recommended to confirm the presence of a plasma cell tumor. Clinical follow-up was available on ten patients; of these, nine were treated with aggressive chemotherapy and, in five instances, additional radiotherapy. The 10th patient succumbed to infection prior to treatment. Nine of the ten patients were dead of disease 3 days to 4 yr following clinical diagnosis of a plasma cell dyscrasia. One patient (Case 1) was lost to follow-up after biopsy confirmation of plasmacytoma. The cytomorphologic appearance of neoplastic plasma cells in FNA of solitary masses necessitates clinical evaluation for bone marrow disease, i.e., myeloma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263589 TI - Hand and digital ischemia due to arteriosclerosis and thromboembolization in young adults: pathologic features with clinical correlations. AB - Twenty young adult patients with hand and digital ischemia were found to have obstructive arterial disease. All patients were surgically explored, and the occluded vessels were resected and by-passed. Eighteen patients had obstruction at the level of the distal ulnar artery and palmar arch, and 12 had obstruction of the common digital and digital proper arteries. Occlusive arteriosclerotic lesions were found in all patients; these lesions were characterized by prominent fibromuscular intimal plaques with superimposed thrombosis. Six patients had also thromboembolism to distal digital vessels. Vasculitis, calcifications, cholesterol deposits, and atheromatous emboli were not observed. Five patients had transmural neovascularization of the lesions in a similar manner to that described in coronary artery lesions. Obstructive lesions due to fibromuscular intimal proliferation with associated thrombosis and/or distal thromboembolization affecting arteries of hands and digits appear to be an important lesion that can affect young patients. PMID- 2263590 TI - Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies. AB - bcl-2 is a marker for the translocation t(14;18)(q32;q21) indicative of follicular B-cell lymphoma. We studied 115 cases of lymphoproliferative disease with the polymerase chain reaction for bcl-2 oncogene using biotin and radiolabeled probes to the major breakpoint and minor cluster regions. Twenty three percent of B-cell lymphomas were positive for bcl-2. These included 12 of 20 cases of nodular follicular center cell lymphoma (nine small cleaved cell, one mixed small and large cell, and two large cell types). bcl-2 translocation was detected in only three of 45 cases of diffuse B-cell lymphoma, and cases of AIDS related malignant lymphoma, monocytoid B-cell lymphoma, and mantle zone lymphoma were all negative. Nonneoplastic lymphoid proliferations were negative for bcl-2 including nine cases of abnormal follicular hyperplasia from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Cases of T cell lymphoma and five cases of Hodgkin's disease were also negative. The polymerase chain reaction for bcl-2 is a rapid, sensitive technique in the evaluation of follicular B-cell proliferations, and the use of biotinylated probes and the alkaline phosphatase reaction eliminates the requirement for radioactive reagents. PMID- 2263591 TI - Chondromyxoid fibroma: report of six cases with immunohistochemical studies. AB - Chondromyxoid fibroma is a rare benign bone tumor of uncertain histogenesis that typically presents as an eccentric lesion in the metaphysis of a long bone of a young adult. We report S-100 positivity in six cases of myxochondroid fibroma, a finding consistent with the cartilaginous nature of the lesion and its possible relation to chondroblastoma. PMID- 2263592 TI - Nucleolar grading of renal cancer. Correlation of frequency and localization of nucleoli to histologic and cytologic grading and stage of renal cell carcinomas. AB - Cytologic-nucleolar grading of carcinomas includes mitotic frequency, mean nuclear size, nuclear variability, degree of chromasia and nucleolar frequency, and the occurrence of singular or multiple, small or large nucleoli in the central or peripheral location. A total of 186 renal cell carcinomas were analyzed cytologically in this respect. The results were correlated to the histologic pattern, tumor stage, and grading. Renal cell carcinomas of low malignancy and stage possess a low nucleolar frequency and small solitary nucleoli in the central location. Highly malignant carcinomas (T3 or T4) are characterized by high nucleolar frequency and multiple prominent nucleoli in the eccentric position. There is no correlation to the histologic pattern. Therefore, the nucleolar status is helpful in grading and determination of prognosis of renal cell carcinomas. PMID- 2263593 TI - Morphology of bronchial epithelium adjacent to adenocarcinoma of the lung. AB - Gross unremarkable bronchi and bronchioles from 22 lobectomy specimens containing primary adenocarcinoma were examined microscopically. Sections were taken from the segment containing the carcinoma and compared with sections taken from uninvolved segments in the same specimen to examine for premalignant lesions. The average tumor size was 3.75 cm (1.5 to 11 cm). The average age of patients was 60.4 yr (29 to 79 yr); 13 were men and nine were women; all were smokers, and the average was 44.1 pack-years (20 to 100 pack-years). Six of the specimens (27%) showed no histologic changes. Focal squamous metaplasia was identified in nine specimens (41%), but in four of the nine (44%), it was not seen in the carcinogenic segment. Focal goblet cell metaplasia was seen in six specimens (27%), but in two of the six (33%), it was not in the carcinogenic segment. Focal basal cell hyperplasia was seen in two specimens (9%) within both the carcinogenic segment and elsewhere. A single focus of mild epithelial dysplasia was found in each of two specimens (9%), but these foci were not in the carcinogenic segment. Focal epithelial regeneration was noted in three specimens (14%), but two of these (66) were not in the carcinogenic segment. Such microscopic abnormalities of respiratory epithelium are associated with cigarette smoking, and each is a potentially premalignant change; however, our study demonstrated no histologically identifiable changes in the respiratory epithelium that consistently mark for premalignant atypia in the lung adenocarcinoma. PMID- 2263595 TI - Flow cytometric DNA and clinicopathologic analysis of Dukes' A&B colonic adenocarcinomas: a retrospective study. AB - We retrospectively evaluated DNA content flow cytometrically in a series of 124 colonic adenocarcinomas selected for uniformity of stage (A and B), anatomical location (right or transverse colon), and treatment (surgical only) in order to precisely define the significance of ploidy. Aneuploid populations were detected in 43% overall and more commonly with advancing stage (31% Stage A versus 45% Stage B), although this trend did not reach statistical significance (P = 0.16). Overall, as well as stage corrected, 5-yr patient survival was higher for patients with diploid range tumors, but not significantly (71% diploid range versus 60% aneuploid, P = 0.19). Dukes' stage, in contrast, was strongly predictive for 5-yr survival (89% Stage A versus 61% Stage B, P less than or equal to 0.005). Abnormal DNA content was significantly associated with increased patient age (P = 0.02) and presence of angiolymphatic invasion (P = 0.013) but not tumor grade (P = greater than or equal to 0.10). We conclude that flow cytometrically determined abnormal DNA content is weakly related to pathologic features of biologic aggressiveness in colonic adenocarcinoma and is less predictive of patient outcome than conventional Duke's stage. PMID- 2263594 TI - Infiltrating leukocyte populations and T-lymphocyte subsets in head and neck squamous cell carcinomas from patients receiving perilymphatic injections of recombinant interleukin 2. A pathologic and immunophenotypic study. AB - Nine patients with squamous cell carcinoma of the oral cavity and oropharynx underwent preoperative perilymphatic administration of recombinant interleukin 2 (rIL-2). A more marked eosinophil and lymphocyte infiltration and more extensive edema than in 13 untreated cases were observed in surgical specimens. Necrosis was present in five of nine cases, but involved no more than 10% of the neoplastic tissue; in three of nine cases, characteristic necrotic changes with intense eosinophil infiltration possibly induced by lymphokines involved the peritumoral soft tissues. Of the tumor-infiltrating lymphocytes, T-lymphocytes (mostly CD4+ cells) prevailed over B-lymphocytes. CD4+ and CD8+ cells were mainly located close to the neoplastic sheets. Moderate amounts of CD38+ and CD11c+ cells (macrophages) and few CD16+ and CD56+ lymphocytes were found in all cases. CD25+ and LAK1+ cells were significantly more numerous in treated than in untreated cases. This suggests that local administration of rIL-2 induces an increase in activated T-lymphocyte subsets infiltrating the neoplastic tissue, thus eliciting a tumor-specific T-lymphocyte reactivity. PMID- 2263596 TI - Variations with age and serum cholesterol level in the topographic distribution of macroscopic aortic atherosclerotic lesions as assessed by image analysis methods. AB - The topographic distribution of macroscopic atherosclerotic lesions in the aorta was studied by image analysis of aortas taken at autopsy from 155 males aged 10 to 54 yr. In both the thoracic and abdominal aorta, fatty streaks (FS) appear before raised lesions (RL) affecting preferential areas located longitudinally along the intercostal ostia, at the aorta bifurcation, and surrounding the points of origin of branches of the abdominal aorta. Later RL appear in the same areas of the aortic intima affected by FS at younger ages. As for the effect of serum total cholesterol (TC) in the progression of atherosclerosis, the prevalent involvement areas by FS and RL were similarly distributed as indicated by our analyses. However, areas showing frequent occurrence of FS and RL in each aortic segment were distributed more extensively at identical areas in the higher serum TC groups than in the lower TC level group. Thus, it can be concluded that FS are the precursor lesions of RL in the aorta and that the serum TC promotes the progression of atherosclerosis. PMID- 2263597 TI - Ciliated gastric cells: a study of their phenotypic characteristics. AB - Ciliated cells are found in the basal segments of antral glands whose superficial segments have undergone intestinal metaplasia. The affected cells resemble antral rather than metaplastic intestinal cells. This impression is supported by the immunohistochemical demonstration of pepsinogen group II production and ultrastructural demonstration of pepsinogen granules in the involved segments. Abnormal ciliogenesis in these cells resembles a possibly reversible change in bronchial epithelium that accompanies stasis of secretion and chronic inflammation. Affected antral cells show an evidence of decreased mitotic activity, but the multiplicity of cilia in each affected cell suggests that they stem from the continuing propagation of centriole-basal bodies. PMID- 2263598 TI - Accuracy of frozen section diagnosis in soft tissue tumors. AB - This study was undertaken to analyze the accuracy of frozen section (FS) diagnosis of 118 soft tissue tumors with respect to the reasons for which the intraoperative consultation was indicated. Fifty-seven frozen sections were performed for the diagnosis of an unknown pathologic process. Complete agreement was established in 40.3% and the correct pathologic process in 43.9%, the diagnosis was deferred in 14%, and the remaining 1.8% were diagnosed incorrectly. Examination for determination of the adequacy of resection margin (22 cases), lymph node or skip metastases (23 cases), residual or recurrent tumor after previous surgery (29 cases), viable tumor tissue after previous locoregional or systemic therapy (ten cases), and identification of the specimen (five cases) proved to be 95.5%, 95.7%, 96.6%, 90%, and 100% accurate. Considering the whole series, an erroneous answer to a question posed by a surgeon was given in four cases (two false positive and two false negative), of which two cases were a sampling error made by pathologist. Intraoperative consultation by FS in soft tissue tumors is (a) reliable for general rather than exact diagnosis in defining the previously unknown pathologic process and (b) mandatory in evaluating resection margins and any discrepancies between preoperative cytologic and intraoperative gross impression. PMID- 2263599 TI - Ideas in pathology. Malignant melanoma in situ: the evolution of a concept. AB - For clinical dermatologists, proliferations of melanocytes confined to the epidermis (and epithelial structures of adnexa) are either flattish melanocytic nevi (junctional type) or flat lesions (macules and patches) of malignant melanoma (malignant melanoma in situ). The same should be true for histopathologists. During the past 30 years, however, histopathologists have avoided making specific diagnoses of malignant melanoma in situ by utilizing a variety of nondiagnostic, euphemistic descriptions for it such as melanotic freckle of Hutchinson, melanosis circumscripta precancerosa of Dubreuilh, active junctional nevus, lentigo maligna, atypical melanocytic hyperplasia, melanocytic dysplasia, and melanocytic intraepithelial neoplasia. Each of these terms evades a specific diagnosis of malignant melanoma in situ, a diagnosis than can, and should, be made clinically and histopathologically if reliable criteria are used. The legitimacy of a concept of malignant melanoma in situ in the context of historical perspective and the importance of that concept for management of patients are the themes of this essay. PMID- 2263600 TI - Distinguished Pathologist Award for 1990. PMID- 2263601 TI - Physiological induction and reversal of focus formation and tumorigenicity in NIH 3T3 cells. AB - NIH 3T3 cells undergo morphological transformation in response to conditions of constrained growth, such as occur in low serum concentrations or at confluence. Transformation is expressed in a small fraction of the cells by the appearance of discrete foci of multiplying cells on a confluent monolayer of quiescent cells. We isolated and expanded cell populations from three dense and three light foci. Cells from each of these populations efficiently reproduced foci of the same morphotype when grown on a background of nontransformed NIH 3T3 cells. Using cultures derived from one of the dense foci (subline D/2), we found that the number of focus-forming units was stable and the cells remained tumorigenic when they were subjected to repeated thrice-weekly passage in 2% calf serum. However, equivalent passage in 10% calf serum eventually rendered the cells incapable of both focus production and tumor formation. The results show that the capacity to produce tumors as well as morphological transformation are produced as a response to physiological constraints of growth and/or metabolism in the absence of carcinogens and that both properties can be reversed by lifting the constraints. This behavior is typical of an adaptational response and, taken together with other supporting evidence, shows that tumorigenesis does not require conventional genetic alteration. PMID- 2263602 TI - Molecular clock of viral evolution, and the neutral theory. AB - Evolution of viral genes is characterized by enormously high speed compared with that of nuclear genes of eukaryotic organisms. In this paper, the evolutionary rates and patterns of base substitutions are examined for retroviral oncogenes, human immunodeficiency viruses (HIV), hepatitis B viruses (HBV), and influenza A viruses. Our results show that the evolutionary process of these viral genes can readily be explained by the neutral theory of molecular evolution. In particular, the neutral theory is supported by our observation that synonymous substitutions always much predominate over nonsynonymous substitutions, even though the substitution rate varies considerably among the viruses. Furthermore, the exact correspondence between the high rates of evolutionary base substitutions and the high rates of production of mutants in RNA viruses fits very nicely to the prediction of the theory. The linear relationship between substitution numbers and time was examined to evaluate the clock-like property of viral evolution. The clock appears to be quite accurate in the influenza A viruses in man. PMID- 2263603 TI - NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. AB - A sensitive DNA-protein crosslinking approach has been used to characterize four inducible T-cell proteins (50 kDa, 55 kDa, 75 kDa, and 85 kDa) that specifically bind to kappa B enhancer elements. Partial proteolytic mapping revealed a distinct cleavage pattern for three of these proteins. These polypeptides are sequestered as inactive precursors in the cytosol of unstimulated T cells but can be converted into active forms in vivo by phorbol ester stimulation or in vitro by detergent treatment. The induction of these proteins by phorbol ester results in a strikingly biphasic pattern of nuclear expression with the 55-kDa and 75-kDa species appearing within minutes, whereas the 50-kDa and 85-kDa species appear only several hours after cellular stimulation. These data suggest that NF-kappa B binding activity may not correspond to a single polypeptide but rather a family of at least four inducible and differentially regulated DNA-binding proteins that are expressed with distinct kinetics in human T lymphocytes. PMID- 2263604 TI - Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes. AB - The circulating T lymphocytes of a female child with recurrent opportunistic infections were normal in number and phenotype but exhibited poor proliferation and decreased synthesis of the T-cell growth factor interleukin (IL) 2 in response to mitogens. Recombinant IL-2 fully restored the proliferative responses of her T cells, suggesting that her poor immune function was related to IL-2 deficiency. Northern blot analysis of total cellular RNA from the patient's T cells revealed markedly decreased levels of IL-2 mRNA of normal size. In addition, mRNA levels of other lymphokines selectively expressed by T cells, which include IL-3, IL-4, and IL-5, were either severely depressed or absent. The levels of interferon gamma mRNA were moderately decreased, while those of granulocyte-macrophage colony stimulating factor, a lymphokine the production of which is not restricted to T cells, were unaffected. The decreased level of lymphokine mRNA in the patient's T lymphocytes was not from enhanced catabolism but resulted from a diminution in the transcription rate of the affected lymphokine genes. Normal transduction via the T-cell receptor/CD3 complex of biochemical signals necessary for the initiation of lymphokine gene transcription indicated that the defect was distal to the membrane signal-transducing apparatus. The defect is hypothesized to involve a T-cell-specific trans-acting regulatory factor required for transcription of the affected lymphokine genes. PMID- 2263606 TI - Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue. AB - We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed. PMID- 2263605 TI - Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. AB - MRL-lpr/lpr mice spontaneously develop a lupus-like syndrome characterized by immunopathological manifestations such as necrotizing vascular lesions of ear tips and severe glomerulonephritis. Similar skin vascular and glomerular lesions associated with cryoglobulinemia can be induced in normal mice by injection of a monoclonal antibody (mAb)--6-19 (gamma 3 heavy chain and kappa light chain), exhibiting both cryoglobulin and anti-IgG2a rheumatoid factor (RF) activities- derived from the MRL-lpr/lpr autoimmune mouse. To determine the role of RF and/or IgG3 Fc fragment-associated cryoglobulin activities in 6-19 mAb-induced tissue lesions, a 6-19-J558L hybrid mAb (gamma 3 heavy chain and lambda 1 light chain) was produced by fusion between the 6-19 hybridoma and the J558L myeloma. Here we report that the 6-19-J558L hybrid mAb, which loses the RF activity but retains the cryoglobulin activity, fails to induce skin vascular lesions. However, it is still able to provoke glomerular lesions identical to those caused by the 6-19 mAb. Further, we have observed that the depletion of the corresponding autoantigen, IgG2a, in mice by treatment with anti-IgM antisera from birth also prevents the development of skin but not glomerular lesions. Our results indicate that both RF and cryoglobulin activities of the 6-19 mAb are required for the development of skin vasculitis, but its cryoglobulin activity alone is sufficient to cause glomerular lesions. In addition, cDNA cloning and sequencing of the 6-19 mAb has revealed that the 6-19 kappa light chain variable region amino acid sequence is encoded in a germ-line configuration, suggesting that immunoglobulin variable region germ-line genes could contribute to the generation of pathogenic autoantibodies. PMID- 2263607 TI - Positive transcriptional feedback at the bvg locus controls expression of virulence factors in Bordetella pertussis. PMID- 2263608 TI - The low-affinity Ca2(+)-binding sites in cardiac/slow skeletal muscle troponin C perform distinct functions: site I alone cannot trigger contraction. AB - Both troponin C (TnC) and calmodulin share a remarkably similar tertiary motif that may be common to other Ca2(+)-binding proteins with activator activity. TnC plays a critical role in regulating muscle contraction and is particularly well suited for structural analysis by site-directed mutation. Fast-twitch skeletal muscle TnC has two low-affinity Ca2(+)-binding sites (sites I and II), while in cardiac and slow-twitch skeletal muscle TnC site I is inactive. Recently, using protein engineering, we directly demonstrated that binding of Ca2+ to the low affinity site(s) initiates muscle contraction. In the present study, we use mutagenesis to determine whether either of the low-affinity sites in cardiac TnC can trigger contraction in slow-twitch skeletal muscle fibers. In one Ca2(+) binding mutant, Ca2(+)-binding to the dormant low-affinity site I was restored (CBM+I). In a second mutant, site I was activated while site II was inactivated (CBM+I-IIA). Both proteins had the predicted CA2(+)-binding characteristics, and both were able to associate with troponin I and troponin T to form a troponin complex and integrate into permeabilized slow-twitch skeletal muscle fibers. A comparison of NMR spectra shows the aromatic regions in the two proteins to be qualitatively similar without divalent cations but markedly different with Ca2+. Mutant CBM+I supported force generation in skinned slow skeletal muscle fibers but had Sr2+ and Ca2+ sensitivities similar to fast skeletal TnC. Mutant CBM+I IIA was unable to restore Ca2(+)-dependent contraction to TnC-depleted skinned slow muscle fibers. The data directly demonstrate that low-affinity sites I and II have distinct functions and that only site II in cardiac TnC can trigger muscle contraction in slow-twitch skeletal muscle fibers. This principle of distinct, modular activities for Ca2(+)-binding sites in the same protein may apply to other members of the TnC/calmodulin family. PMID- 2263610 TI - Cell line-specific differences in the control of cell cycle progression in the absence of mitosis. AB - This paper reports that there are major differences between mammalian cell lines in the propensity to progress into subsequent cell cycles when mitosis is inhibited with agents that disrupt the assembly of the mitotic spindle apparatus (Colcemid, nocodazole, and taxol). Human HeLa S3 cells, which represent one extreme, remain arrested in mitosis, with elevated levels of cyclin B and p34cdc2 kinase activity. In Chinese hamster ovary cells, at the other extreme, the periodic rise and fall of cyclin B levels and p34cdc2 kinase activity is only transiently inhibited in the absence of mitosis. The cells progress into subsequent cell cycles, without dividing, resulting in serial doublings of cellular DNA content. In general, the propensity to progress into subsequent cell cycles in the absence of mitosis appears to be species related, such that human cell lines remain permanently blocked in a mitotic state, whereas rodent cell lines are only transiently inhibited when spindle assembly is disrupted. We interpret these results to indicate that in mammalian cell lines there exists a checkpoint which serves to couple cell cycle progression to the completion of certain karyokinetic events. Furthermore, either such a checkpoint exists in some cell lines but not in others or the stringency of the control mechanism varies among different cell lines. PMID- 2263609 TI - Adenovirus early region 4 stimulates mRNA accumulation via 5' introns. AB - The adenovirus major late transcription unit accounts for most virus-specific transcription late after infection. All mRNAs expressed from this unit carry a short spliced leader, the so-called tripartite leader, attached to their 5' ends. Here we describe a function for an adenovirus gene product in the control of major late mRNA abundance. We show that early region 4 (E4) stimulates mRNA accumulation from tripartite leader intron-containing transcription units approximately 10-fold in short-term transfection assays. The effect was already detectable in nuclear RNA and was not due to a transcriptional activation through any of the major late promoter elements or through an effect at nuclear to cytoplasmic mRNA transport. A surprising positional effect of the intron was noted. To be E4 responsive, the intron had to be placed close to the pre-mRNA 5' end. The same intron located far downstream in the 3' untranslated region of the mRNA was not E4 responsive. The E4 enhancement was not dependent on specific virus exon or intron sequences. These results suggest that E4 modulates a general pathway in mammalian mRNA formation. PMID- 2263611 TI - Molecular mechanisms in down-regulation of tumor necrosis factor expression. AB - Excessive production of tumor necrosis factor (TNF) after stimulation by lipopolysaccharide (LPS) may result in fever, intravascular coagulation, and lethal shock. An efficient way of preventing the excessive TNF production is desensitization of monocytes/macrophages to LPS. We have analyzed the molecular mechanisms involved in the induction of desensitization and the mechanisms operative in the desensitized, LPS-refractory cells by employing the human monocytic cell line Mono-Mac-6. Similar to human blood monocytes, treatment of Mono-Mac-6 cells with LPS (1 microgram/ml) results in a rapid and transient expression of TNF. When Mono-Mac-6 cells are precultured in medium containing low levels of LPS, they become refractory to subsequent LPS stimulation and show no or little secretion of TNF protein. Desensitization can be blocked by the inhibition of cyclooxygenase and protein kinase C; both prostaglandin E2 (together with a second signal) and phorbol 12-myristate 13-acetate can mimic desensitization. By employing prostaglandin E2 and low concentrations of phorbol 12-myristate 13-acetate, a synergism in the induction of desensitization can be demonstrated. Hence, our studies show that two distinct pathways are involved in the induction of hyporesponsiveness. In both LPS-responsive and LPS-desensitized Mono-Mac-6 cells, LPS was able to induce the transcription factor NF-kappa B in the nucleus. Still, the prevalence of TNF-specific mRNA was dramatically reduced in the desensitized cells. These data indicate that LPS-desensitized Mono-Mac-6 cells are able to activate initial steps of signal transduction up to the level of the NF-kappa B transcription factor. The absence of TNF transcripts, however, indicates that additional nuclear factors may be missing or that silencers may be active such that transcription of the TNF gene is prevented. PMID- 2263612 TI - High-resolution structure of a mutagenic lesion in DNA. AB - The self-complementary dodecanucleotide d[CGC(m6G)AATTTGCG]2 (where m6G is O6 methylguanine), which contains two m6G.T base pairs, has been analyzed by x-ray diffraction methods and the structure has been refined to a residual error of R = 0.185 at 2.0-A resolution. The m6G.T mispair closely resembles a Watson-Crick base pair and there are very few structural differences between the m6G.T duplex and the native analogue. The similarity between the m6G.T base pair and a normal G.C base pair explains the failure of mismatch repair enzymes to recognize and remove this mutagenic lesion. A series of ultraviolet melting studies over a wide pH range on a related dodecamer indicate that the m6G.C mispair can exist in two conformations; one is a wobble pair and the other is a protonated Watson-Crick pair. The former, which predominates at physiological pH, will be removed by normal proofreading and repair enzymes, whereas the latter is likely to escape detection. Hence, the occasional occurrence of the protonated m6G.C base pair may explain why the presence of m6G in genomic DNA does not always give rise to a mutation. PMID- 2263613 TI - Analysis of interleukin 2 and various effector cell populations in adoptive immunotherapy of 9L rat gliosarcoma: allogeneic cytotoxic T lymphocytes prevent tumor take. AB - Recombinant interleukin 2 (rIL-2) and various effector cell populations were used for adoptive immunotherapy in the Fischer strain 9L rat gliosarcoma model. The in vivo cytotoxicities of nonspecifically activated lymphocytes and specifically activated cytotoxic T lymphocytes (CTLs) were assessed in a modified in vivo neutralization (Winn) assay. Effector cells (10(6)) and 9L tumor cells (10(5] were combined with 10(4) units of rIL-2 and stereotactically implanted into the right frontal centrum semiovale of the Fischer (F344) rat. At 7 and 14 days, additional effector cells (10(6] and rIL-2 (10(4) units) were administered through the same burr hole. Nonspecifically activated splenocytes were lymphokine activated killer (LAK) cells, both plastic-adherent and nonadherent, whereas specifically activated CTLs were either syngeneic (genetically identical) or allogeneic (genetically dissimilar). Syngeneic CTLs were T lymphocytes from Fischer rats primed in vivo with 9L cells and restimulated in vitro. Allogeneic CTLs were generated by exposing DA rat lymphocytes either to irradiated Fischer lymph node cells or to 9L Fisher tumor cells in vitro. Control groups included rats bearing 9L tumor who were untreated, those who received peripheral (i.p. or s.c.) administration of rIL-2, or those who received syngeneic unstimulated T lymphocytes and rIL-2. For a set of animals given the same inoculum of 9L tumor, significantly improved survival was shown for groups treated with nonadherent or adherent LAK cells (P less than or equal to 0.0003), syngeneic CTLs (P = 0.0327), or allogeneic CTLs (P = 0.0025) over untreated control animals by using Mantel Haenzel nonparametric logrank equations. Only treatment with allogeneic CTLs prevented tumor take. PMID- 2263614 TI - A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo. AB - The murine gene for adipocyte P2 encodes an adipocyte-specific member of the family of intracellular lipid binding proteins. The region upstream from the start of transcription of this gene has been found to contain binding sites for the transcription factors c-jun/c-fos and C/EBP (CCAAT/enhancer binding protein) and several short sequence elements found in other adipocyte gene promoters, termed fat-specific elements. To identify DNA sequences that were responsible for the high level of transcription of the gene for adipocyte P2 in vivo, we made a series of transgenic mice containing 168 base pairs (bp), 247 bp, 1.7 kilobases (kb), and 5.4 kb of 5' flanking sequence linked to the bacterial gene chloramphenicol acetyltransferase. Although plasmids containing only 168 bp of 5' sequence including the C/EBP and AP-1 (activation protein 1) binding sites were expressed well in cultured adipocytes, high levels of chloramphenicol acetyltransferase activity in the adipose tissue of transgenic mice were not observed until the 5' flanking region was extended to kb -54. An enhancer mapping between kb -4.9 and kb -5.4 upstream from the start of transcription was identified by transfection of further deletions into cultured adipocytes. This enhancer, when linked to a bp -63 promoter fragment from the gene for adipocyte P2, directed very high level chloramphenicol acetyltransferase expression specifically to adipose tissue in transgenic mice. These results identify a functional adipose-specific enhancer and indicate that it is the major determinant of tissue specificity of the gene for adipocyte P2. These results also demonstrate that the proximal-promoter binding sites for AP-1 and C/EBP are not sufficient or necessary to give adipose-tissue-specific expression in vivo, though they may play an important role in the response of this promoter to glucocorticoids. PMID- 2263615 TI - Dynamics of the distribution of cyclic AMP-dependent protein kinase in living cells. AB - The intracellular distribution of regulatory molecules may provide a mechanism for controlling gene expression. The subcellular location of cAMP-dependent protein kinase was analyzed in living cells by microinjection of regulatory and catalytic subunits labeled with fluorescein. Following microinjection, type I holoenzyme was found in the cytoplasm and remained there for up to 4 hr. Upon dissociation of holoenzyme with 8-bromo-cAMP, free catalytic subunit appeared in the nucleus while regulatory subunit remained in the cytoplasm. Similarly, purified catalytic subunit was transported to the nucleus in the absence of elevated intracellular cAMP following its introduction into the cytoplasm. Translocation to the nucleus was apparent within 10 min and persisted for at least 2 hr. In contrast, purified regulatory subunit, like holoenzyme, was maintained in the cytoplasm. These results suggest that one function of the type I regulatory subunit is to serve as a cytoplasmic anchor, sequestering the catalytic subunit in the cytoplasm until holoenzyme dissociates in response to increased cAMP. PMID- 2263616 TI - Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region. AB - Argininosuccinic acid lyase (ASAL) deficiency is a clinically heterogeneous autosomal recessive urea cycle disorder. We previously established by complementation analysis that 28 ASAL-deficient patients have heterogeneous mutations in a single gene. To prove that the ASAL structural gene is the affected locus, we sequenced polymerase chain reaction-amplified ASAL cDNA of a representative mutant from the single complementation group. Fibroblast strain 944 (approximately 1% of residual ASAL activity), from a late-onset patient who was the product of a consanguineous mating, had only a single base-pair change in the coding region, a C-283----T transition at a CpG dinucleotide in exon 3. This substitution converts Arg-95 to Cys (R95C), occurs in a stretch of 13 residues that is identical in yeast and human ASAL, and was present in both of the patient's alleles but not in 14 other mutant or 10 normal alleles. Expression in COS cells demonstrated that the R95C mutation produces normal amounts of ASAL mRNA but little protein and less than 1% ASAL activity. We observed that amplified cDNA from mutant 944 and normal cells (liver, keratinocytes, lymphoblasts, and fibroblasts) contained, in addition to the expected 5' 513-base pair band, a prominent 318-base-pair ASAL band formed by the splicing of exon 2 from the transcript. The short transcript maintains the ASAL reading frame but removes Lys-51, a residue that may be essential for catalysis, since it binds the argininosuccinate substrate. We conclude (i) that the identification of the R95C mutation in strain 944 demonstrates that virtually all ASAL deficiency results from defects in the ASAL structural gene and (ii) that minor alternative splicing of the coding region occurs at the ASAL locus. PMID- 2263617 TI - Transcriptional regulation of interleukin 3 gene expression in T lymphocytes. AB - Interleukin 3 (IL-3 or multi-colony-stimulating factor) plays an important role in the hematopoietic response to inflammatory stimuli through its action on both immature and mature blood cells. Like other lymphokines, IL-3 is produced in response to activation of the T-cell receptor and protein kinase C pathways. By using nuclear run-on assays of quiescent and stimulated T-cell lines, we demonstrate that IL-3 gene expression is controlled, at least in part, at the level of transcription. Functional reporter gene analysis was used to delineate two regions of the IL-3 5' flanking sequence responsible for transcriptional stimulation. DNA binding proteins that potentially mediate these responses were then recognized by mobility-shift and DNase footprinting assays. One region responsible for transcriptional enhancement was localized to the sequence GATGAATAAT, the cognate site of a transcription factor, here termed NF-IL3-A. A second region of functional activity and protein binding was localized to a single transcription factor AP-1 site. In addition three functionally inhibitory regions were identified. These results, along with the further characterization of NF-IL3-A, will contribute to the understanding of IL-3 gene regulation in stimulated T cells. PMID- 2263618 TI - Stability and activity of human immunodeficiency virus protease: comparison of the natural dimer with a homologous, single-chain tethered dimer. AB - A single-chain tethered dimer of human immunodeficiency virus protease (HIV-PR) was produced by expression of a synthetic gene in Escherichia coli. The tethered dimer, which consists of two 99-amino acid HIV-PR subunits linked together by a pentapeptide, was isolated from inclusion bodies and refolded as an active protease with enzymatic properties very similar to those of the natural dimer at pH 5.5. In addition to demonstrating that the tethered dimer is active, we have shown that the tethered dimer is more stable than the natural HIV-PR dimer at pH 7.0. This is attributed to dissociation of the natural HIV-PR dimer, for which a surprisingly high dissociation constant, 5 X 10(-8) M was measured. Furthermore, the tethered dimer offers an opportunity to produce asymmetric dimer mutants and thereby determine the effect of changes in one of the two subunits on protease activity. In one such mutant, a single active-site aspartic residue was changed to a glycine residue. This protein was inactive, consistent with a requirement for an aspartic residue from each subunit to constitute an active site of HIV-PR. PMID- 2263619 TI - Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. AB - To study the primary structure of human acetylcholinesterase (AcChoEase; EC 3.1.1.7) and its gene expression and amplification, cDNA libraries from human tissues expressing oocyte-translatable AcChoEase mRNA were constructed and screened with labeled oligodeoxynucleotide probes. Several cDNA clones were isolated that encoded a polypeptide with greater than or equal to 50% identically aligned amino acids to Torpedo AcChoEase and human butyrylcholinesterase (BtChoEase; EC 3.1.1.8). However, these cDNA clones were all truncated within a 300-nucleotide-long G + C-rich region with a predicted pattern of secondary structure having a high Gibbs free energy (-117 kcal/mol) downstream from the expected 5' end of the coding region. Screening of a genomic DNA library revealed the missing 5' domain. When ligated to the cDNA and constructed into a transcription vector, this sequence encoded a synthetic mRNA translated in microinjected oocytes into catalytically active AcChoEase with marked preference for acetylthiocholine over butyrylthiocholine as a substrate, susceptibility to inhibition by the AcChoEase inhibitor BW284C51, and resistance to the BtChoEase inhibitor tetraisopropylpyrophosphoramide. Blot hybridization of genomic DNA from different individuals carrying amplified AcChoEase genes revealed variable intensities and restriction patterns with probes from the regions upstream and downstream from the predicted G + C-rich structure. Thus, the human AcChoEase gene includes a putative G + C-rich attenuator domain and is subject to structural alterations in cases of AcChoEase gene amplification. PMID- 2263620 TI - Dopamine induces neurite retraction in retinal horizontal cells via diacylglycerol and protein kinase C. AB - Dopamine causes a significant retraction of neurites of bull-head catfish horizontal cells maintained in culture. The effects of dopamine are blocked by haloperidol and SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. The dopamine-induced morphological changes were mimicked by SKF 38393, a D1 agonist, but not by quinpirole, a D2 agonist. Kainate also caused process retraction, but other neuroactive substances tested including glutamate, 5-hydroxytryptamine, N-methyl-D-aspartate, gamma-aminobutyric acid, and glycine caused only minor changes in neurite length. Cyclic AMP analogues do not induce neurite retraction in horizontal cells, indicating that this effect of dopamine is not mediated by cyclic AMP. However, a protein kinase C activator (phorbol 12 myristate 13-acetate) and synthetic diacylglycerol analogs (1-oleoyl-2-acetyl-sn glycerol and dioctanoglycerol) caused marked neurite retraction. Their effects, as well as the dopamine-induced changes, were blocked by staurosporine, a potent protein kinase antagonist. The results suggest that dopamine causes neurite retraction by the activation of protein kinase C via diacylglycerol. PMID- 2263622 TI - Expression of the thymus leukemia antigen in mouse intestinal epithelium. AB - The Qa and Tla regions of the mouse major histocompatibility complex contain a series of genes encoding proteins with structural similarity to the class I transplantation antigens of the same complex. In contrast to the genes encoding the transplantation antigens, the Qa and Tla genes show very little polymorphism. Function(s) of the proteins encoded by the Qa and Tla loci remain an enigma. Recently, the protein products of the Qa and Tla loci, often referred to as class Ib major histocompatibility complex molecules, have been proposed to present antigen to gamma delta T cells. In mice, gamma delta T cells have been found concentrated in several epithelial barriers and in the skin; yet, expression of serologically detectable Tla antigens is believed restricted to thymocytes, activated T lymphocytes, and some T-cell leukemias. Here we report that luminal epithelial cells of the mouse small intestine express the thymus leukemia antigen (TLA). We also find that, unlike T cells in Peyer's patches, a significant fraction of intestinal epithelial lymphocytes also express TLA. RNA prepared from intestinal cells contains transcripts of the T18d gene, which encodes TLA. These data extend the known expression profile of TLA molecules to mature lymphocytes and to nonhematopoietic cells. These data also demonstrate the specific expression of TLA on antigen-presenting cells in a site enriched for T cells that express gamma delta T-cell antigen receptor. PMID- 2263621 TI - Involvement of transforming growth factor alpha in the release of luteinizing hormone-releasing hormone from the developing female hypothalamus. AB - Little is known about the presence of trophic factors in the hypothalamus and the role they may play in regulating the functional development of hypothalamic neurons. We have investigated the ability of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) to affect the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls reproductive development. We have also determined whether the genes encoding EGF and TGF-alpha are expressed in the prepubertal female hypothalamus. Northern blot analysis of poly(A)+ RNA utilizing a single-stranded EGF cDNA probe failed to reveal the presence of EGF mRNA in either the hypothalamus or the cerebral cortex at any age studied (fetal day 18 to postnatal day 36). In contrast, both a complementary RNA probe and a double-stranded TGF-alpha cDNA recognized in these regions a 4.5 kilobase (kb) mRNA species identical to TGF-alpha mRNA. The abundance of TGF alpha mRNA was 3-4 times greater in the hypothalamus than in the cerebral cortex. Both EGF and TGF-alpha (2-100 ng/ml) elicited a dose-related increase in LHRH release from the median eminence of juvenile rats in vitro. They also enhanced prostaglandin E2 (PGE2) release. The transforming growth factors TGF-beta 1 and beta 2 were ineffective. Only a high dose of basic fibroblast growth factor was able to increase LHRH and PGE2 release. Blockade of the EGF receptor transduction mechanism with RG 50864, a selective inhibitor of EGF receptor tyrosine kinase activity, prevented the effect of both EGF and TGF-alpha on LHRH and PGE2 release but failed to inhibit the stimulatory effect of PGE2 on LHRH release. Inhibition of prostaglandin synthesis abolished the effect of TGF-alpha on LHRH, indicating that PGE2 mediates TGF-alpha-induced LHRH release. The results indicate that the effect of EGF and TGF-alpha on LHRH release is mediated by the EGF/TGF-alpha receptor and suggest that TGF-alpha rather than EGF may be the physiological ligand for this interaction. Since in the central nervous system most EGF/TGF alpha receptors are located on glial cells, the results also raise the possibility that--at the median eminence--TGF-alpha action may involve a glial neuronal interaction, a mechanism by which the trophic factor first stimulates PGE2 release from glial cells, and then PGE2 elicits LHRH from the neuronal terminals. PMID- 2263623 TI - Polymorphism at the self-incompatibility locus in Solanaceae predates speciation. AB - Sequences of 11 alleles of the gametophytic self-incompatibility locus (S locus) from three species of the Solanaceae family have recently been determined. Pairwise comparisons of these alleles reveal two unexpected observations: (i) amino acid sequence similarity can be as low as 40% within species and (ii) some interspecific similarities are higher than intraspecific similarities. The gene genealogy clearly illustrates this unusual pattern of relationships. The data suggest that some of the polymorphism at the S locus existed prior to the divergence of these species and has been maintained to the present. In support of this hypothesis, the number of shared polymorphic sites was found to exceed the number found in simulations with independent accumulation of mutations. Strictly neutral evolution is exceedingly unlikely to maintain the polymorphism for such a long time. The allele multiplicity and extreme age of the alleles is consistent with Wright's classic one-locus population genetic model of gametophytic self incompatibility. Similarities between the plant S locus and the mammalian major histocompatibility complex are discussed. PMID- 2263624 TI - Phospholipase A2 activity of low density lipoprotein: evidence for an intrinsic phospholipase A2 activity of apoprotein B-100. AB - During oxidative modification of low density lipoprotein (LDL) there is extensive degradation of phosphatidylcholine (PtdCho) to lysophosphatidylcholine (lyso PtdCho), with the removal of fatty acids from the 2 position. The phospholipase A2 (PLA2) activity responsible for hydrolysis is closely associated with LDL. By use of lipoxygenase-oxidized 2-[1-14C]linoleoyl PtdCho as the substrate and delipidated apoprotein B (apo-B), evidence is presented to show that (i) the activity is destroyed progressively during the oxidative modification of LDL; (ii) p-bromophenacyl bromide (pBPB), a histidine modifier that inhibits the oxidative modification of LDL, also substantially inhibits the PLA2 activity; and (iii) photooxidation of LDL in the presence of Rose Bengal completely inactivates the enzyme with concomitant loss of apo-B histidine residues. High molecular weight proteins from delipidated LDL, separated by polyacrylamide gel electrophoresis, showed PLA2 activity. It is suggested that apo-B itself may possess PLA2 activity. PMID- 2263625 TI - A different cytochrome P450 form is induced in primary cultures of rat hepatocytes. AB - A 49-kDa protein (P49) was discovered in the primary cultures of rat hepatocytes. P49 cross-reacted with the antibodies against purified P450IIC11 [formerly P 450(M-1)]. P49 was located in microsomes and highly induced after plating of isolated hepatocytes on collagen-coated culture dishes. To characterize P49, cDNA clones were screened from a rat liver lambda gt11 expression library. From sequence analysis of the cloned cDNAs, the amino acid sequence of P49 was deduced, and the protein was identified as a previously uncharacterized form of cytochrome P450. P49 consists of 489 amino acids and shows approximately 60% similarity with the members of class IIC subfamily of rat cytochrome P450, such as P450IIC11 and P450IIC12 [formerly P-450(F-1)]. RNA blot analysis indicates that the mRNA translating P49 was induced approximately 20- to 30-fold at 70 hr in the primary cultures compared with the liver of adult rats. Induction of P49 was not affected by density of the plated cells and the presence or absence of several hormones, serum, or antibiotics in the culture medium. On the other hand, lower induction of P49 was seen when the hepatocytes were cultured on Matrigel coated plates. Expression of P49 mRNA was low in the liver of adult rats and was not detectable in the livers of 1- and 2-week-old male and female rats. P49 is an additional form of cytochrome P450, which is induced in the primary culture of rat hepatocytes. PMID- 2263626 TI - In vitro regulation of a SIN3-dependent DNA-binding activity by stimulatory and inhibitory factors. AB - The yeast SIN3 gene (also known as SDII, is a known negative regulator of the yeast HO gene. A DNA-binding activity, called SDP1, which binds to the HO promoter, is absent in extracts prepared from sin3 mutants and has been proposed to function as a repressor. We show that SIN3 does not encode SDP1 and that SDP1 DNA-binding activity is modulated in vitro by two factors, an inhibitory factor, I-SDP1, and a stimulatory factor, S-SDP1. I-SDP1 acts as an in vitro inhibitor of the SDP1 DNA-binding activity. Restoration of the DNA-binding activity is achieved by inclusion of a stimulatory factor, S-SDP1, which copurifies with the SIN3 protein. SDP1 DNA-binding activity was restored by treating a protein fraction containing SDP1 and I-SDP1 with the dissociating agent formamide. PMID- 2263627 TI - Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon. AB - It was reported two decades ago that insulin was not detectable in the glucose stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled pork insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report we describe the purification and amino acid sequences of squirrel monkey insulin and glucagon. We demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in our immunoassay system is only a few percent of that of human insulin. Squirrel monkey glucagon is identical with the usual glucagon found in Old World mammals, which predicts that the glucagons of other New World monkeys would not differ from the usual Old World mammalian glucagon. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species. PMID- 2263628 TI - Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. AB - We have identified a region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter that is necessary for maximal constitutive, virus-induced, and lipopolysaccharide (LPS)-induced transcription. This region contains three sites that match an NF-kappa B binding-site consensus sequence. We show that these three sites specifically bind NF-kappa B in vitro, yet each of these sites can be deleted from the TNF-alpha promoter with little effect on the induction of the gene by virus or LPS. Moreover, when multimers of these three sites are placed upstream from a truncated TNF-alpha promoter, or a heterologous promoter, an increase in the basal level of transcription is observed that is influenced by sequence context and cell type. However, these multimers are not sufficient for virus or LPS induction of either promoter. Thus, unlike other virus- and LPS inducible promoters that contain NF-kappa B binding sites, these sites from the TNF-alpha promoter are neither required nor sufficient for virus or LPS induction. Comparison of the sequence requirements of virus induction of the human TNF-alpha gene in mouse L929 and P388D1 cells reveals significant differences, indicating that the sequence requirements for virus induction of the gene are cell type-specific. However, the sequences required for virus and LPS induction of the gene in a single cell type, P388D1, overlap. PMID- 2263629 TI - Cell mutants defective in synthesizing a heparan sulfate proteoglycan with regions of defined monosaccharide sequence. AB - We have demonstrated that mouse LTA cells synthesize cell-surface heparan sulfate proteoglycans (HSPGs) with regions of defined monosaccharide sequence that specifically interact with antithrombin (HSPGact). It remains unclear how HSPGact can be generated by a biosynthetic pathway with no simple template for directing the ordered assembly of monosaccharide units. To examine this issue, we treated LTA cells with ethyl methanesulfonate and then isolated seven stable mutants that synthesize only 8-27% of the wild-type HSPGact but produce normal amounts of other HSPGs. These mutants are recessive in nature and fall into at least two different complementation groups. The delineation of the molecular basis of these defects should help to elucidate the manner by which cells synthesize HSPGs with regions of defined monosaccharide sequence. PMID- 2263630 TI - Boron neutron capture therapy of intracerebral rat gliosarcomas. AB - The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation. PMID- 2263631 TI - Cloning of cDNAs encoding amphibian bombesin: evidence for the relationship between bombesin and gastrin-releasing peptide. AB - Bombesin is a tetradecapeptide originally isolated from frog skin; its mammalian homologue is the 27-amino acid peptide gastrin-releasing peptide (GRP). cDNAs encoding GRP have been cloned from diverse species, but little is yet known about the amphibian bombesin precursor. Mass spectrometry of HPLC-separated skin exudate from Bombina orientalis was performed to demonstrate the existence of authentic bombesin in the skin of this frog. A cDNA library was prepared from the skin of B. orientalis and mixed oligonucleotide probes were used to isolate cDNAs encoding amphibian bombesin. Sequence analysis revealed that bombesin is encoded in a 119-amino acid prohormone. The carboxyl terminus of bombesin is flanked by two basic amino acids; the amino terminus is not flanked by basic amino acids but is flanked by a chymotryptic-like cleavage site. Northern blot analysis demonstrated similarly sized bombesin mRNAs in frog skin, brain, and stomach. Polymerase chain reaction was used to show that the skin and gut bombesin mRNAs encoded the identical prohormones. Prohormone processing, however, differed between skin and gut. Chromatography showed the presence of only authentic bombesin in skin whereas gut extracts contained two peaks of bombesin immunoreactivity, one consistent in size with bombesin and one closer in size to mammalian GRP. Thus the same bombesin prohormone is processed solely to bombesin in skin but is processed to a peptide similar in size to bombesin and to a peptide similar in size to mammalian GRP in stomach. PMID- 2263632 TI - A myo-inositol pool utilized for phosphatidylinositol synthesis is depleted in sciatic nerve from rats with streptozotocin-induced diabetes. AB - Peripheral nerve from experimentally diabetic rats exhibits lowered levels of myo inositol (MI) and decreased incorporation of [3H]MI into phosphatidylinositol (PI). There are indications that diminished PI turnover may be causally related to reduced Na+,K(+)-ATPase activity in diabetic nerve. We have investigated whether a metabolic compartment of MI that is essential for PI synthesis is decreased in this tissue. Sciatic nerve segments from streptozotocin-induced diabetic and age-matched normal rats were incubated in vitro with either 32Pi or [3H]cytidine in the presence of propranolol. This cationic amphiphilic agent redirected nerve phospholipid metabolism to produce enhanced 32P incorporation into PI and decreased labeling of phosphatidylcholine and phosphatidyl ethanolamine. The accumulation of phosphatidyl CMP (CMP-PA) was also demonstrated by chromatographic and enzymatic means. The incorporation of [3H]cytidine into CMP-PA in normal nerve increased up to 15-fold when 0.6 mM propranolol was present. In diabetic nerve, the liponucleotide incorporated 2- to 3-fold more isotope and was more readily labeled at lower drug concentrations as compared to normal nerve. The buildup of [3H]CMP-PA was reduced in a dose-dependent manner in the presence of MI in the incubation medium at concentrations up to 3 mM. However, if MI was added after liponucleotide accumulation, preformed CMP-PA could not be utilized for PI synthesis. The difference in liponucleotide labeling between normal and diabetic nerve was nearly abolished at 0.3 mM medium MI, a concentration much less than the level of cyclitol in the tissue. These results strongly suggest the presence in nerve of a pool of MI that is not in equilibrium with the bulk of nerve MI and that is preferentially used for PI synthesis. This metabolic compartment is depleted in diabetic nerve but can be readily replenished by exogenous MI and may correspond to the MI pool that has been proposed to be required for the turnover of a portion of tissue PI involved in maintenance of normal Na+,K(+)-ATPase activity. PMID- 2263633 TI - Structural alterations of nerve during cuff compression. AB - Whether compression nerve injury is due to ischemia, direct mechanical injury, or both remains unsettled. To assess structural changes of nerve during compression, peroneal nerves of rats were compressed at various pressures for different times, and the structural alterations were stopped by simultaneous in situ and perfusion fixation. The structural changes observed during a few minutes of compression cannot be explained by ischemic injury because the pathologic alterations characteristic of ischemia take many hours to develop and in any case are different from the ones found here. The pressure- and time-related structural changes observed in the present study under the cuff were (i) decrease in fascicular area and increase in fiber density due to expression of endoneurial fluid; (ii) compression and expression of axoplasm, sometimes to the point of fiber transection; (iii) lengthening of internodes; and (iv) obscuration of nodes of Ranvier due to cleavage and displacement of myelin and overlapping of nodes by displaced loops of myelin. At the edges of the cuff the changes were (i) increase of fascicular area probably from expressed endoneurial fluid; (ii) widening of nodal gaps, perhaps mainly from translocated axonal fluid; and (iii) disordered structure of axoplasm. We suggest that the process of paranodal demyelination and axonal transection are linked, occur during the act of compression, and are due to shear forces. The initial event is expression of endoneurial fluid, followed by compression and expression of axoplasm and cleavage and displacement of layers of myelin. Conceivably, with prolonged cuff compression ischemic injury might be found to be superimposed on mechanical injury. PMID- 2263634 TI - Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro. AB - Intercellular coupling was studied in cultured rat optic nerve astrocytes individually characterized by A2B5 antibody staining. The presence of cell coupling was assessed by injecting single cells with the low molecular weight fluorescent dye Lucifer yellow and noting dye passage into adjacent cells; cell coupling was also studied by analyzing the decay phase of current transients recorded in response to small voltage steps using whole-cell patch-clamp recording. Cell coupling was restricted to A2B5- astrocytes, the majority of which had a flat fibroblast-like appearance and was never observed in A2B5+ stellate-shaped astrocytes. Furthermore, A2B5- astrocytes showed coupling only to A2B5- and never to A2B5+ astrocytes. Analysis of current transients provided an additional indicator for cell coupling. Astrocytes that showed dye coupling to at least one neighboring cell required the sum of two exponential functions to fit current transients, whereas a single exponential function sufficed to fit transients in cells that were not dye coupled. The specificity of cell coupling in cultured rat optic nerve astrocytes suggests that predominantly A2B5- astrocytes comprise a coupled glial syncytium; this physiological feature of these cells may be a specialized adaptation for "spatial buffering," the transport of K+ away from areas of focal extracellular accumulation. On the other hand, A2B5+ astrocytes form an uncoupled subpopulation of rat optic nerve glial cells that may serve different functions. PMID- 2263635 TI - Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1. AB - The homeodomain-containing transcription factor hepatocyte nuclear factor 1 (HNF 1) most likely plays an essential role during liver organogenesis by transactivating a family of greater than 15 predominantly hepatic genes. We have isolated cDNA clones encoding mouse HNF-1 and expressed them in monkey COS cells and in the human T-cell line Jurkat, producing HNF-1 DNA-binding activity as well as transactivation of reporter constructs containing multimerized HNF-1 binding sites. In addition, the HNF-1 gene was assigned by somatic cell hybrids and recombinant inbred strain mapping to mouse chromosome 5 near Bcd-1 and to human chromosome 12 region q22-qter, revealing a homologous chromosome region in these two species. The presence of HNF-1 mRNA in multiple endodermal tissues (liver, stomach, intestine) suggests that HNF-1 may constitute an early marker for endodermal, rather than hepatocyte, differentiation. Further, that HNF-1 DNA binding and transcriptional activity can be conferred by transfecting the HNF-1 cDNA into several cell lines indicates that it is sufficient to activate transcription in the context of ubiquitously expressed factors. PMID- 2263636 TI - Identification of transforming growth factor beta family members present in bone inductive protein purified from bovine bone. AB - Characterization of the polypeptides present in bone-inductive protein extracts from bovine bone has led to the cloning of seven regulatory molecules, six of which are distantly related to transforming growth factor beta. The three human bone morphogenetic proteins (BMPs) we describe herein, BMP-5, BMP-6, and BMP-7, show extensive sequence similarity to BMP-2, a molecule that by itself is sufficient to induce de novo bone formation in vivo. The additive or synergistic contribution of these BMP-2-related molecules to the osteogenic activity associated with demineralized bone is strongly implicated by the presence of these growth factors in the most active fractions of highly purified bone extract. PMID- 2263637 TI - Cytochrome a1 of acetobacter aceti is a cytochrome ba functioning as ubiquinol oxidase. AB - Cytochrome a1 is a classic cytochrome that in the 1930s had already been detected in Acetobacter strains and in the 1950s was identified as a terminal oxidase. However, recent studies did not substantiate the previous observations. We have detected a cytochrome a1-like chromophore in Acetobacter aceti, which was purified and characterized in this study. The cytochrome was solubilized from membranes of the strain with octyl beta-D-glucopyranoside and was purified by single column chromatography. The purified cytochrome exhibited a broad alpha peak around 600-610 nm, which turned to a sharp peak at 589 nm in the presence of cyanide. Carbon monoxide difference spectra of the cytochrome indicated the presence of an alpha-type cytochrome. The cytochrome contained 1 mol each of hemes b and a and probably one copper ion. These results suggest that the cytochrome purified from A. aceti is the so-called cytochrome a1, and thus the existence of the classic cytochrome has been reconfirmed. The purified enzyme consisted of four polypeptides of 55, 35, 22, and 18 kDa, and it showed a sedimentation coefficient of 6.3 S in the native form. The enzyme had a high ubiquinol oxidase activity (140-160 mumol of ubiquinol-2 oxidized per min per mg of protein). When reconstituted into proteoliposomes, the cytochrome could generate an electrochemical proton gradient during oxidation of ubiquinol. Thus, cytochrome a1 of A. aceti has been shown to be a cytochrome ba terminal oxidase capable of generating an electrochemical proton gradient concomitant with ubiquinol oxidation. PMID- 2263638 TI - Uv-visible spectroscopy of bacteriorhodopsin mutants: substitution of Arg-82, Asp 85, Tyr-185, and Asp-212 results in abnormal light-dark adaptation. AB - The light-dark adaptation reactions of a set of bacteriorhodopsin (bR) mutants that affect function and color of the chromophore were examined by using visible absorption spectroscopy. The absorbance spectra of the mutants Arg-82 in equilibrium Ala (Gln), Asp-85 in equilibrium Ala (Asn, Glu), Tyr-185 in equilibrium Phe, and Asp-212 in equilibrium Ala (Asn, Glu) were measured at different pH values during and after illumination. None of these mutants exhibited a normal dark-light adaptation, which in wild-type bR causes a red shift of the visible absorption maximum from 558 nm (dark-adapted bR) to 568 nm (light-adapted bR). Instead a reversible light reaction occurs in the Asp-85 and Asp-212 mutants from a blue form with lambda max near 600 nm to a pink form with lambda max near 480 nm. This light-induced shift explains the appearance of a reversed light adaptation previously observed for the Asp-212 mutants. In the case of the Tyr-185 and Arg-82 mutants, light causes a purple-to-blue transformation similar to the effect of lowering the pH. However, the blue forms observed in these mutants are not identical to those formed by acid titration or deionization of wild-type bR. It is suggested that in all of these mutants, the chromophore has lost the ability to undergo the normal 13-cis, 15-syn to all trans, 15-anti light-driven isomerization, which occurs in native bR. Instead these mutants may have as stable forms all-trans,syn and 13-cis,anti chromophores, which are not allowed in native bR, except transiently. PMID- 2263639 TI - Repair of O6-ethylguanine in DNA protects rat 208F cells from tumorigenic conversion by N-ethyl-N-nitrosourea. AB - O6-Ethylguanine (O6-EtGua) is one of about a dozen different alkylation products formed in the DNA of cells exposed to the alkylating N-nitroso carcinogen N-ethyl N-nitrosourea (EtNU). We have evaluated selectively the relative capacity of cells for the specific enzymatic repair of O6-EtGua as a determinant for the probability of malignant conversion. Eleven O6-EtGua-repair-proficient (R+) variant subclones were isolated from the O6-EtGua-repair-deficient (R-) clonal rat fibroblast line 208F by selection for resistance to 1,3-bis-(2-chloroethyl)-1 nitrosourea (frequency, approximately equal to 10(-5). Contrary to the 208F wild type cells, all variants expressed O6-methylguanine-DNA methyltransferase activity, while both kinds of cells were deficient for repair of the DNA ethylation products O2- and O4-ethylthymine. After exposure to EtNU (less than or equal to 500 micrograms/ml; 20 min), cells were analyzed for the formation of piled-up foci in monolayer culture and of anchorage-independent colonies in semisolid agar medium. Depending on the EtNU concentration, the frequencies of piled-up foci and agar colonies, respectively, in the R+ variants were as low as 1/28th and 1/56th of those in the R- wild type. Contrasting with the cells from R+ variant-derived agar colonies, cells from 208F (R-) agar colonies gave rise to highly malignant tumors when implanted subcutaneously into syngeneic rats. No significant differences in the frequencies of piled-up foci were found between wild-type and variant cells after exposure to the major reactive metabolite of benzo[a]pyrene, (+)-7 beta, 8 alpha-dihydroxy-9,10 alpha-epoxy-7,8,9,10 alpha tetrahydrobenzo[a] pyrene, for which stable binding to guanine O6 in cellular DNA has not been observed. The relative capacity of cells for repair of O6 alkylguanine is, therefore, a critical determinant for their risk of malignant conversion by N-nitroso carcinogens. PMID- 2263640 TI - Glucose-induced translocation of protein kinase C in rat pancreatic islets. AB - The role of protein kinase C (PKC) as a mediator of glucose-induced insulin secretion has been a subject of controversy. Glucose-induced translocation of PKC has not been reported, and the relevant PKC isoenzymes in islets have not been identified. To address these issues, we developed specific antibodies to the alpha, beta, and gamma isoenzymes of PKC. Western blots of homogenates of freshly isolated rat islets probed with these antibodies revealed that the major isoenzyme present is alpha-PKC. Islets were perifused for 15 min with either 2.75 mM glucose, 20 mM glucose, 20 mM glucose plus 30 mM mannoheptulose, 15 mM alpha ketoisocaproate, or alpha-ketoisocaproate plus mannoheptulose. Quantitative immunoblotting of membrane and cytosol fractions showed that alpha-PKC translocated from the cytosol to the membrane in freshly isolated rat islets stimulated with either 20 mM glucose or 15 mM alpha-ketoisocaproate. Both the secretory response and the translocation of alpha-PKC were blocked by the addition of mannoheptulose, an inhibitor of glucose metabolism, in islets stimulated with glucose but not in islets stimulated with alpha-ketoisocaproate. These results support a role for alpha-PKC in mediating glucose-induced insulin secretion in pancreatic islets. PMID- 2263641 TI - Characterization of iron superoxide dismutase cDNAs from plants obtained by genetic complementation in Escherichia coli. AB - The inability of superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1)-deficient mutants of Escherichia coli to grow aerobically on minimal medium can be restored by functional complementation with a heterologous SOD encoding sequence. Based upon this property, a phenotypic selection system has been developed for the isolation of clones containing eukaryotic SOD cDNAs. cDNA expression libraries from both Nicotiana plumbaginifolia and Arabidopsis thaliana were transformed into a SOD-deficient E. coli strain by electroporation, and clones containing functional SODs were selected by growth on minimal medium. Analysis of these clones revealed the identity of cDNAs encoding the iron form of superoxide dismutase (FeSOD)--the first SODs of this type to be cloned from eukaryotes. The presence of this enzyme in these two divergent plant species challenges previous ideas that FeSOD is found in only a few plant families. In addition, these results show the potential for shotgun cloning of eukaryotic genes by complementation of bacterial mutants, particularly when it is combined with a highly efficient transformation method, such as electroporation. PMID- 2263642 TI - Meiotic recombination between yeast artificial chromosomes yields a single clone containing the entire BCL2 protooncogene. AB - The common translocation found in human follicular lymphoma, t(14;18)(q32;q21), results in deregulation of the BCL2 protoonocogene. The isolation of the intact gene would provide an essential substrate to analyze the molecular basis of this malignancy. Pulsed-field gel electrophoresis suggested that this three-exon gene was several hundred kilobases (kb) long. Therefore, a library of yeast artificial chromosome (YAC) clones was screened to isolate the intact BCL2 gene. Two clones, yA85B6 (200 kb) and yB206A6 (700 kb), were isolated by using polymerase chain reaction (PCR) assays specific for exon I/II and exon III, respectively. However, neither YAC contained the entire BCL2 locus. Since the two YACs were found to overlap by 60 kb, we sought to take advantage of the high recombination frequency in yeast and induce physical recombination between the two clones. Cells containing each YAC were mated and induced to undergo meiotic division and sporulation. Analysis of the resulting tetrads revealed a spore containing a single recombinant YAC of 800 kb. PCR assays and Southern blotting demonstrated that this recombined YAC contained the entire approximately 230-kb BCL2 gene. Furthermore, probe order was conserved and there was no evidence of overt rearrangements or deletions. These results indicate the feasibility of reconstructing large genomic segments with overlapping YAC clones to study genes spanning hundreds of kilobases. PMID- 2263643 TI - Homologous recombination at c-fyn locus of mouse embryonic stem cells with use of diphtheria toxin A-fragment gene in negative selection. AB - In attempting to produce a mutant mouse with embryonic stem cells, the critical step is the efficient isolation of homologous recombinants; the frequency of the homologous recombination is usually low and the potency of the cells to differentiate into germ cells is unstable in culture. Here, we report an efficacious method for such isolation in which the diphtheria toxin A-fragment gene is used to negatively select nonhomologous recombinants. In contrast to the use of the herpes simplex virus thymidine kinase gene, the selection can be made singly by the neomycin analog G418 without using a drug such as ganciclovir, a nucleoside analog. At the c-fyn locus, the diphtheria-toxin negative selection enriched the recombinants about 10-fold, and half of the cells integrating with the neomycin phosphotransferase gene were homologous recombinants. PMID- 2263644 TI - Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. AB - The activation of nuclear factor kappa B (NF-kappa B) has been implicated in the regulation of transcription of a variety of genes and has been shown to be essential for the expression of genes controlled by the long terminal repeat of human immunodeficiency virus (HIV LTR). We show here that intracellular thiol levels play a key role in regulating this process. That is, stimulation with tumor necrosis factor alpha and/or phorbol 12-myristate 13-acetate activates NF kappa B and markedly decreases intracellular thiols; N-acetyl-L-cysteine, an efficient thiol source, prevents this thiol decrease and blocks the activation of NF-kappa B; and the lack of activated NF-kappa B prevents the activation of the HIV LTR and the transcription of genes under its control. These findings reveal a previously unrecognized genetic regulatory mechanism in which cytokine-induced shifts in intracellular thiol levels are crucial in the control of NF-kappa B activity and thereby influence the spectrum of genes expressed by cytokine stimulated cells. PMID- 2263645 TI - Evidence that down-regulation of beta-cell glucose transporters in non-insulin dependent diabetes may be the cause of diabetic hyperglycemia. AB - Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facilitative glucose transporter expressed by beta cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume of GLUT-2-positive beta cells and a reduction at the electron-microscopic level in the number of GLUT-2 immunoreactive sites per unit of beta-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal beta cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in beta cells of prediabetic ZDF rats by elimination of hyperglycemia. We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia. PMID- 2263646 TI - Frequent mutation of the p53 gene in human esophageal cancer. AB - Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. We examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9. Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G.C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus. PMID- 2263647 TI - Cytogenetic damage induced by folate deficiency in mice is enhanced by caffeine. AB - Folate deficiency in Swiss mice increased the incidence of micronuclei in peripheral blood erythrocytes, indicating increased chromosomal damage in nucleated erythrocyte precursors. Caffeine enhanced the incidence of micronuclei in blood and bone marrow by up to 5-fold in folate-deficient mice at doses that did not significantly alter the micronucleus frequency in the presence of adequate dietary folate. The lower dose of caffeine used in this study (75 mg/kg) approaches doses received by humans who consume large amounts of caffeinated beverages. Since folate deficiency and caffeine consumption are highly prevalent in the human population, the potential for a similar interaction in man should be evaluated. PMID- 2263649 TI - Behavioral correlates of a progressive dysfunctioning of the deeper layers of the colliculus superior: effects of picrotoxin. AB - Intracaudate injections of relatively high doses of apomorphine produce a regression in motor behavior of cats collecting food pellets in a treadmill design (25). It has been hypothesized that this regression is partly due to functional disturbances in brain regions receiving (in) directly striatal output signals. In view of this hypothesis it was investigated whether experimentally induced changes in GABAergic activity within the deeper layers of the colliculus superior, which is a second order output station of the caudate nucleus, are also able to elicit a regression in motor behavior. Therefore, motor behavior of cats was tested in the treadmill paradigm before and after intracollicular injections of the GABA antagonist picrotoxin. Picrotoxin produced dose-dependently a regression in motor behavior which was comparable to that elicited by intrastriatally injected apomorphine. The noted effects were GABA-specific since muscimol attenuated the picrotoxin-induced regression. The present data are discussed in view of a model for a hierarchical organization of the brain. PMID- 2263650 TI - Improvement of cold tolerance by selective A1 adenosine receptor antagonists in rats. AB - Previously we have shown that the improvement of cold tolerance by theophylline is due to antagonism at adenosine receptors rather than inhibition of phosphodiesterase. Since theophylline is a nonselective adenosine receptor antagonist for both A1 and A2 receptors, the present study investigated the adenosine receptor subtype involved in theophylline's action. Acute systemic injection of selective A1 receptor antagonists (1,3-dialkyl-8-aryl or 1,3-dialkyl 8-cyclopentyl xanthine derivatives) significantly increased both the total and maximal heat production as well as cold tolerance. In contrast, injection of a relatively selective A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (compound No. 19), failed to significantly alter the thermogenic response of the rat under cold exposure. Further, the relative effectiveness of these compounds in increasing total thermogenesis was positively correlated with their potency in blocking the A1 adenosine receptor (r = .52, p less than 0.01), but not in A2 adenosine receptor (r = .20, p less than 0.2). It is likely that the thermally beneficial effects of adenosine A1 antagonists are due to their attenuation of the inhibitory effects of endogenously released adenosine on lipolysis and glucose utilization, resulting in increased substrate mobilization and utilization for enhanced thermogenesis. PMID- 2263648 TI - Conserved enzymes mediate the early reactions of carotenoid biosynthesis in nonphotosynthetic and photosynthetic prokaryotes. AB - Carotenoids comprise one of the most widespread classes of pigments found in nature. The first reactions of C40 carotenoid biosynthesis proceed through common intermediates in all organisms, suggesting the evolutionary conservation of early enzymes from this pathway. We report here the nucleotide sequence of three genes from the carotenoid biosynthesis gene cluster of Erwinia herbicola, a nonphotosynthetic epiphytic bacterium, which encode homologs of the CrtB, CrtE, and CrtI proteins of Rhodobacter capsulatus, a purple nonsulfur photosynthetic bacterium. CrtB (prephytoene pyrophosphate synthase), CrtE (phytoene synthase), and CrtI (phytoene dehydrogenase) are required for the first three reactions specific to the carotenoid branch of general isoprenoid metabolism. The homologous proteins from E. herbicola and R. capsulatus show sequence identities of 41.7% for CrtI, 33.7% for CrtB, and 30.8% for CrtE. E. herbicola and R. capsulatus CrtI also display 27.2% and 27.9% sequence identity, respectively, with R. capsulatus CrtD (methoxyneurosporene dehydrogenase). All three dehydrogenases possess a hydrophobic N-terminal domain containing a putative ADP binding beta alpha beta fold characteristic of enzymes known to bind FAD or NAD(P) cofactors. In addition, E. herbicola and R. capsulatus CrtB show 25.2% and 23.3% respective sequence identities with the protein product of pTOM5, a tomato cDNA of unknown function that is differentially expressed during fruit ripening. These data indicate the structural conservation of early carotenoid biosynthesis enzymes in evolutionarily diverse organisms. PMID- 2263651 TI - Behavioral performance effects of nicotine in smokers and nonsmokers. AB - Performance on finger-tapping and handsteadiness, tasks opposite in response requirements, was compared between male smokers and nonsmokers (n = 10 each) on two occasions, once following intake of nicotine (15 micrograms/kg) by measured dose nasal spray and once following placebo. Compared with nonsmokers, smokers had significantly greater increase in finger-tapping speed due to nicotine. On the other hand, smokers tended to have improved performance on handsteadiness (i.e., less involuntary movement) due to nicotine, while nonsmokers had impaired performance, although this difference was not significant. Nicotine-induced changes in performance on each task were inversely related, suggesting specificity of the behavioral effects of nicotine depending on task demands, rather than a generalized effect. These effects of nicotine on behavioral performance may be important in understanding the reinforcing value of nicotine intake, and differences in effects as a function of smoking history may suggest chronic adaptation to nicotine. PMID- 2263653 TI - Relationship of the behavioral effects of aprophen, atropine and scopolamine to antagonism of the behavioral effects of physostigmine. AB - Behavioral effects of aprophen, atropine and scopolamine, in rats, were examined under a multiple schedule of food presentation and at different injection-test times. The effects of the varied treatments were compared to the ability of the drugs, under identical conditions, to prevent the behavioral effects of the anticholinesterase, physostigmine. Potencies of the antagonists to decrease response rates varied across three log units. All three antagonists produced dose related attenuation of the response suppressant effects of physostigmine. In general, aprophen was a better antagonist than scopolamine or atropine. It blocked behavioral effects of physostigmine across a wider range of doses than the other compounds, and did so with less behavioral disruption. Although substantial differences between the three antagonists were observed, the behavioral effects of all three antagonists (when administered alone) were positively correlated with their efficacy as antagonists of the response suppressant effects of physostigmine. PMID- 2263652 TI - Microinjections of a nicotinic agonist into dopamine terminal fields: effects on locomotion. AB - Nicotine induces locomotion, a behavior associated with the mesocorticolimbic dopamine system. The present study determined the effects on locomotion of direct microinjections of the nicotinic agonist cytisine into four DA terminal fields were nicotinic receptors have been localized: nucleus accumbens (NAS, n = 20), caudate putamen (CPU, n = 9), olfactory tubercle (OT, n = 8), and medial prefrontal cortex (MPC, n = 12). Male Long-Evans rats were injected with cytisine (0.1, 1, 10 and 100 nanomoles per 0.5 microliters per side) or vehicle through indwelling cannulae, and locomotor activity was recorded during a 60-minute test session; each animal was tested with each dose in counterbalanced order. NAS injections of the three highest doses of cytisine increased locomotion relative to vehicle injections; injections in the CPU, dorsal to the NAS, were ineffective, as were MPC and OT injections. The data support the notion that systemic nicotine may interact with dopaminergic projections to the NAS to produce increases in locomotor activity. PMID- 2263654 TI - Modulation by estrogen and progesterone of the effect of muscimol on nociception in the spinal cord. AB - The GABAA agonist, muscimol, administered intrathecally (IT) to the spinal cord at a dose (1 microgram) that was subthreshold for affecting pain thresholds (vocalization-threshold-to-tail-shock: VTTS, and tail-flick latency: TFL) in ovariectomized, hormonally untreated rats, showed a significant increase in VTTS up to 30 min postinjection in intact females only in proestrus or estrus. This treatment produced no significant effect on TFL at any stage of the estrous cycle. IT muscimol produced a significant increase in VTTS (but not TFL) in ovariectomized rats primed with estradiol benzoate (EB) for 2 days and tested 40 hr after the second injection but had no effect in females primed with a single EB injection and tested 15 min later. By contrast, ovariectomized females primed with progesterone (P) for 15 min exhibited a significant increase in pain thresholds after IT muscimol in both the VTTS and TFL tests. When EB-primed females (2 days) received P 4 hr prior to muscimol there was no analgesia produced by IT muscimol, in contrast to EB-primed females receiving P 15 min prior to IT muscimol in which there was significant analgesia. These results suggest a mechanism for antagonistic effects of estrogen and progesterone. PMID- 2263655 TI - Enhanced sensitivity to quipazine in the genetically dystonic rat (dt). AB - Both normal and genetically dystonic (dt) rats show a high-frequency forepaw tremor in response to systemic administration of the serotonin (5-HT) agonist quipazine at 8 days of age. The response declines with age in normal, but not dystonic, rats. By 16 days of age and after the development of a generalized movement disorder, the dystonic rat exhibits enhanced sensitivity to the tremorogenic effects of the drug in comparison with normal rats. Tremor was blocked by pretreatment with ketanserin, suggesting that it is mediated by 5-HT2 receptors. The dystonic rat has previously been shown to be insensitive to the tremorogenic effects of harmaline, a drug presumed to act indirectly through serotonergic neurons. This finding, coupled with the increased sensitivity to quipazine, suggests the presence of an abnormality in serotonergic systems in the mutants. Since there is evidence of abnormality in the olivo-cerebellar system in the dystonic rat, the alternative hypothesis that a nonserotonergic defect in the olivo-cerebellar system accounts for both the failure of behavioral response to harmaline and the persistent expression of a response to quipazine is also discussed. PMID- 2263656 TI - Behavioral effects of neural transplants into the intact striatum. AB - The behavioral effects of fetal brain tissue and adrenal medulla transplants into the intact striatum of rats were investigated. Following a bilateral injection of 1.5, 3 or 6 microliters of fetal striatal tissue, a volume-related weight loss was found in all transplanted groups, including the SHAM group, during the first 7 days after the surgery. Rearing behavior was changed in a transplant volume related manner. Histological analysis suggested that the locomotor effects of transplants into the intact striatum are related to the volume of the transplants. Following bilateral transplantation of fetal cortex (CTX), substantia nigra (SN), striatum (STR), or adrenal medulla (AM) into the striatum, the different behavioral deficits were observed among these transplant groups. The SN group showed a decrease in spontaneous locomotion, significantly increased rearing activity in response to administration of amphetamine, reduction of food intake and water intake and a reduction in body weight. The CTX and AM groups showed a marked increase in spontaneous rearing activities. Hyporesponsiveness to the administration of apomorphine (1 mg/kg) and amphetamine (1 mg/kg) was evident in the CTX, STR, AM groups and SHAM groups. In contrast, the haloperidol-induced catalepsy scores of the CTX, STR, SN and AM were significantly higher than those of a normal control group. In addition, the CTX group showed a deficit in the delayed reward alternation test. These results indicated that the behavioral deficits produced by transplants into normal striatum may be related to both mechanical destruction due to transplant expansion and specific neurochemical interactions of each tissue type between the host and the transplant. Therefore, potential negative consequences of neural transplantation therapy should be considered as well as the beneficial effects. PMID- 2263657 TI - Effects of physostigmine on operant serial discrimination/reversal learning in rats. AB - Two experiments examined the effects of physostigmine on acquisition and performance of operant serial reversals by rats. In Experiment 1, four groups of rats (n = 6/group) were injected with either vehicle or 0.03 mg/kg physostigmine five minutes prior to each session, or vehicle or 0.5 mg/kg physostigmine immediately after each session of a three-stimulus (bright, dim or flashing light) repeated discrimination/reversal procedure. Rats treated with physostigmine pre- or postsession learned significantly more reversals over 50 sessions than animals injected with vehicle. Experiment 2 used only two discriminative stimuli, a light and a 2,500 Hz tone. Following establishment of a stable daily reversal baseline, postsession injections of physostigmine significantly increased the number of trials to criterion on the next session compared to each subject's control baseline. Results are attributed to enhanced between-session transfer of previously learned discriminated instrumental responses by physostigmine-treated animals. PMID- 2263658 TI - Strain, sex and developmental profiles of cocaine metabolizing enzymes in mice. AB - Cocaine is a potent hepatotoxin in laboratory mice, although the cocaine-induced hepatotoxicity (CIH) is due to the action of a metabolite of cocaine. Cocaine can be hydrolyzed by serum cholinesterase (ChE) to inactive products, or be oxidized by hepatic cytochrome P-450 and FAD-containing monooxygenase (FADM). The oxidative pathway is thought to be responsible for production of the hepatotoxic metabolite of cocaine, presumably norcocaine nitroxide. Female mice are much more resistant to CIH than males of the same strain. We have found that immature male mice are as resistant as females to the development of CIH. Males did not show any CIH until the onset of puberty (30 days of age), indicating that the development of CIH in males was under hormonal control. To determine if the major cocaine-metabolizing enzymes were responsible for the regulation of CIH, we measured the activities of ChE, cocaine N-demethylation (CND) and FADM as a function of sex in C57BL/6Ibg and DBA/2Ibg mice 20-21, 30 +/- 1 and 65 +/- 5 days of age. There was a significant sex difference in ChE activity (females higher than males) but no effect of age. Cocaine N-demethylation increased in both males and females with age, but there was no consistent sex difference. Activity of FADM declined in males as a function of age, but remained constant in females. The lack of a consistent correlation between enzyme activities and sex-, strain-, and age-dependent differences in susceptibility to CIH, do not support a regulatory role for ChE, CND or FADM in mediating the hepatotoxic response. PMID- 2263659 TI - Population characteristics and cigarette yield as determinants of smoke exposure. AB - Relationships of population characteristics, smoking history, and cigarette yield with smoke exposure as measured by peripheral blood concentrations of thiocyanate, carboxyhemoglobin, nicotine and cotinine were sought in 170 male smokers. This population of smokers had significant elevations of serum thiocyanate, blood carboxyhemoglobin and plasma nicotine and cotinine concentrations as compared with an equal number of age- and sex-matched nonsmokers and these concentrations correlated significantly with past 24-hour cigarette consumption. Although the nicotine yield of the cigarette correlated significantly with plasma cotinine and marginally with plasma nicotine, the reduction in plasma nicotine and cotinine was not proportionate to the reduced yield of the cigarettes, suggesting that smokers partially compensate for the lower yields of their cigarettes. Blood levels of carboxyhemoglobin, nicotine and cotinine were also significantly associated with the weight of the subjects, presumably due to the relationship between weight and the volume of distribution. Univariate and multiple regression analyses provided evidence that coffee and alcohol consumption and years smoked also may be important determinants of smoke exposure. PMID- 2263661 TI - Pontine lesions attenuate physostigmine suppression of self-stimulation in the rat. AB - In male Wistar albino rats with chronically implanted electrodes, self stimulation behavior was compared before and after making bilateral pontine lesions involving the subcoeruleus area and adjacent tegmental field. Before lesioning, slight suppression of bar pressing after subcutaneous injection of 0.05 mg/kg physostigmine, marked stable suppression after 0.1 mg/kg, and very strong suppression after 0.2 mg/kg were observed. After making pontine lesions, the suppressive effects of physostigmine were clearly attenuated. With 0.05 and 0.1 mg/kg, no effect or only occasional slight suppression was observed in most cases. With 0.2 mg/kg, total suppression was induced in association with some peripheral effects, but the duration was obviously less than in the prelesion controls. Control saline injection did not produce a suppressive effect. From these findings, it is suggested that suppression of self-stimulation by physostigmine up to 0.1 mg/kg is due to the inhibition of motor activity through the cholinoceptive dorso-lateral pontine tegmental area and not due to a direct effect on the forebrain cholinergic process, presumably involving reinforcement or motivation. PMID- 2263660 TI - Chronic anxiolytic treatment effects on conflict behavior in the rat. AB - The present studies examined the effects of chronic posttest treatment with the antipanic agent alprazolam (ALP) or the traditional anxiolytic agents chlordiazepoxide (CDP) and phenobarbital (PhB) on conflict behavior. In daily ten minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.25 or 0.5 mA). Electrification was signalled by a tone. Chronic ALP (10 mg/kg/day), CDP (40 mg/kg/day), PhB (80 mg/kg/day) or vehicle were injected IP after conflict testing (in some experiments again 12-16 hours later) for a minimum of 6 weeks. Chronic ALP (but not CDP or PhB) resulted in a time-dependent increase in punished responding, with a latency to onset of 3 4 weeks; this effect was not antagonized by the benzodiazepine antagonist Ro15 1788. These data support the hypothesis that conflict paradigms may serve as animal models for the study of antipanic agents. Moreover, these data suggest that not all anxiolytics will exhibit antipanic efficacy. PMID- 2263662 TI - Diurnal variation of phenylpropanolamine anorexia in rats. AB - An examination of the effects of the diurnal cycle on phenylpropanolamine (PPA) anorexia was conducted using two groups of rats, differentiated on the basis of time (Night or Day) of drug injection (0, 10, 20, or 30 mg/kg PPA). The results demonstrate that PPA, over a range of doses, has greater anorectic potency during the dark phase of the diurnal cycle. Moreover, the effect of PPA on water intake was not influenced by the diurnal cycle, suggesting that the diurnal effect was limited to the inhibitory action of PPA on feeding. Other studies are cited which, combined with the present results, suggest that the diurnal cycle may modulate feeding control processes, and that the impact of an anorectic agent such as PPA on feeding behavior may be, in part, a function of the diurnal cycle. PMID- 2263663 TI - Conditioned tolerance provides protection against ethanol lethality. AB - To produce conditioned drug tolerance, mice were given twice daily injections of 3.5 g/kg of ethanol for four days and were tested on the fifth day in the same environment or in a novel environment. A range of doses of ethanol were utilized on the test day to assess lethality. The LD50 for ethanol was higher in mice tested in the environment previously associated with the administration of ethanol than in those tested in a novel environment. Therefore, conditioned tolerance can provide protection against ethanol lethality. PMID- 2263664 TI - Puffing topography as a determinant of smoke exposure. AB - Puffing topography variables were measured in a well-characterized, male population smoking their own brand of cigarette. Of the puffing topography variables, interpuff interval appeared to be the primary determinant of blood concentrations of smoke constituents: however, preliminary data in a homogeneous population according to the nicotine yield of their cigarette suggest that total puff volume per cigarette may also be a significant determinant of blood levels of smoke constituents. Smokers of low nicotine yield cigarettes partially compensated for these lower yields by increasing the total volume puffed per cigarette. Observed differences in puffing topography associated with increased daily cigarette consumption and cumulative smoking history were consistent with a higher smoke exposure per cigarette. Further, although both alcohol and coffee consumption are associated with present and cumulative smoking history, coffee consumption is uniquely associated with differences in puffing topography consistent with a higher smoke exposure per cigarette. However, by multiple regression analyses, neither coffee nor alcohol consumption histories added significantly to the prediction of blood concentrations of smoke constituents over that obtained by smoking history and puffing topography. PMID- 2263665 TI - Retrieval effects of both post- and presession beta-endorphin administration in a three-session paradigm. AB - Rats were submitted to three sessions, with a 24-hr interval between, of step down inhibitory avoidance task using a 60-Hz, 0.3-mA footshock, or of two-way active avoidance task using 25 presentations of a 5-sec. 1-kHz tone and a 0.4-mA footshock. Animals received intraperitoneal injections of either saline or beta endorphin (2.0 microgram/kg) after the first session, and before the second or the third sessions, in a 2 x 2 x 2 design. beta-Endorphin given before the second or the third sessions improved retention for both tasks, but when administered after the first session, it impaired retention for the second session. The administration of beta-endorphin after the first session prevented the retrieval enhancement by the opioid given before the third session. Rats receiving beta endorphin both after the first and before the second sessions, whilst showing no retrieval impairment on the second session, also did not show the pre-third session beta-endorphin retrieval enhancing effect. These data suggest that the post-first session exaggeration of the endogenous opioid state by beta-endorphin administered after the first session causes a long-lasting change in retrievability for the active and inhibitory avoidance tasks, as shown by the lack of the retrieval enhancing effect of beta-endorphin given before the third session. PMID- 2263666 TI - Effects of vinburnine on experimental models of learning and memory impairments. AB - Retrograde amnesia can be induced experimentally in mice by injecting them with scopolamine (3 mg/kg, IP) or by inducing seizures with pentylenetetrazol (50 mg/kg, IP), and in rats by subjecting them to hypobaric hypoxia (at a barometric pressure of 300 mmHg for 3 min). We have studied the effects of vinburnine (VNB) in these amnesic states compared to vincamine (VNC) and nicergoline (NCG), in order to assess its activity on drug-induced learning and memory impairments. Vinburnine reduced the disrupting effect of both scopolamine and pentylenetetrazol-induced seizures on the retention of a step-through passive avoidance behavior in mice and on the acquisition of shuttle-box active avoidance behavior in rats. This effect was dose-related up to 20 mg/kg, the peak effect dose after IP administration, and more pronounced than that of VNC and NCG in some tests. These results indicate that VNB influences learning and memory processes disrupted by a pharmacological manipulation. In particular, as scopolamine acts as anticholinergic drug, it is possible that VNB mechanism of action includes also a stimulation of acetylcholine neurotransmission. PMID- 2263668 TI - Central and peripheral effects of oxytocin administration in prairie voles (Microtus ochrogaster). AB - The present study examined the hypothesis that oxytocin (OT) may influence female sexual behavior in prairie voles (Microtus ochrogaster). The effectiveness of OT to induce sexual behavior was tested in ovariectomized females that were injected daily with estradiol benzoate (EB, 0.02 micrograms, twice), a dose insufficient for estrus induction. On the third day females received intracerebroventricular (ICV) injections of OT (1, 300, or 1000 ng) or saline vehicle. In the presence of minimal estrogen stimulation, OT did not induce sexual receptivity, or influence autogrooming or other social interactions. The behavioral effects of OT were examined in another group of ovariectomized females that received daily oil or EB injections (10 micrograms, twice) followed on the third day by either ICV (1, 300, or 1000 ng) or intraperitoneal (IP) (1, 3, or 10 micrograms) injections of OT. Among EB-treated females, only those in confirmed estrus, prior to ICV or IP injection, were included in these studies. There was a dose-related decrease in the percentage of females that remained in behavioral estrus after ICV OT. In those females that continued to show sexual behavior, lordosis frequencies and durations were unaffected by ICV OT. Nonsexual behavior did not differ between mated females and those exhibiting OT-inhibited sexual behavior. In females that were EB-treated, autogrooming and side-by-side behavior increased after ICV OT, while there was a decline in aggression. Female sexual and nonsexual behaviors were not significantly affected by IP OT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263667 TI - Withdrawal from chronic nicotine fails to produce a conditioned taste aversion to saccharin in rats. AB - Sprague-Dawley rats were maintained on a daily regimen of nicotine, morphine or saline administration for 28 days. Following the discontinuation of the daily drug regimen, rats were given a choice of tap water or a saccharin-water solution. The rats previously receiving morphine drank significantly less saccharin-water solution than did the rats receiving nicotine or saline injections. The failure of the nicotine rats to display a conditioned aversion to the novel saccharin flavor suggests that nicotine did not produce a physiological withdrawal syndrome analogous to morphine withdrawal in this paradigm. PMID- 2263669 TI - Influence of kynurenine treatment on open-field activity, elevated plus-maze, avoidance behaviors and seizures in rats. AB - In the present studies the effects of single and daily repeated injections of kynurenine were investigated in different behavioral tests in rats. In open-field behavior a single injection of kynurenine decreased rearing activity, while the effect was more pronounced after repeated injections. Similarly, in the elevated plus-maze, kynurenine attenuated the total number of entries in the four arms of the equipment, and after chronic treatment decreased the time spent in the open arms (control: 24%; kynurenine 100 mg/kg: 16%; kynurenine 200 mg/kg: 13%). Kynurenine did not influence the passive avoidance learning paradigm (learning session and avoidance latency) and the extinction of active avoidance response. Kynurenine slightly attenuated the kainic acid-induced wet dog shakes and forelimb clonic activity with rearing. These findings suggest that kynurenine (especially after repeated peripheral injections) inhibited several behavioral responses of the experimental animals. However, in one type of highly motivated experimental paradigm (fear from the foot shock), behavioral depression was not detectable. PMID- 2263670 TI - Effects of apomorphine on novelty-induced place preference behavior in rats. AB - Adult male rats were exposed to one of two different stimulus compartments by being placed into the compartment for 30 min on each of eight consecutive days. Following this exposure, each rat was administered 0, 0.05, 0.1, 0.5 or 5.0 mg/kg apomorphine. Thirty min after injection, each animal was given free-choice access to the familiar (exposed) compartment and to the novel (nonexposed) compartment. As expected, saline-injected control animals displayed a preference for the novel compartment. This novelty preference was disrupted in animals given either 0.05 or 0.1 mg/kg apomorphine, but not in animals given either 0.5 or 5.0 mg/kg apomorphine. The disruption in novelty preference by the low doses of apomorphine did not reflect a disruption of locomotor activity, as there was no direct relationship between the preference for novelty and the rate of horizontal or vertical activity among the different treatment groups. Instead, the low doses of apomorphine may have inhibited dopamine function by blocking presynaptic autoreceptors selectively, and thus the reinforcing effect of the novel stimulation may have been attenuated. PMID- 2263671 TI - Pharmacological characterization of ear-scratch response in mice as a behavioral model for selective 5-HT2-receptor agonists and evidence for 5-HT1B- and 5-HT2 receptor interactions. AB - (+/-) 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], a phenylisopropylamine hallucinogen, is a 5-HT2-receptor agonist. The drug induced a dose-dependent increase in ear-scratch response (ESR) in mice, and the R(-) isomer was more than 6 times as potent as its S(+)-enantiomer. The induced behavior was potently inhibited by selective 5-HT2-receptor antagonists such as ketanserin and spiperone. The (+/-)-DOI-induced ESR is also inhibited by stimulation of 5-HT1-receptors and the inhibition seems to be through a 5-HT1B receptor mechanism. Thus, taken together, the present investigation indicates that ESR is due to selective stimulation of 5-HT2-receptors and that simultaneous costimulation of 5-HT1B-receptors inhibits the induced behavior. The study further suggests that the inability of the indolealkylamine hallucinogens to induce ESR is due to simultaneous excitation of 5-HT1B-receptors which are inhibitory to induction of ESR. Moreover, the data suggest possible inhibitory control mechanisms through 5-HT1-receptor subtypes to provide a damping mechanism to reduce excessive 5-HT2-receptor excitation due to exogenous drug stimulation or pathological conditions. PMID- 2263672 TI - Effects of potassium supplementation on blood pressure, electrolytes and 3H norepinephrine release in spontaneously hypertensive rats. AB - Potassium supplementation has been shown to decrease blood pressure in human and animal models of hypertension. The purpose of this study was to determine if potassium supplementation altered sympathetic nerve activity by altering 3H norepinephrine release in caudal artery preparations of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Supplementation in the drinking water with 0.5 or 1.0% KCl for 5 weeks lowered blood pressure (19 and 25 mm Hg, respectively) in SHR but had no effect on WKY. The decrease in blood pressure with 0.5% KCl was not accompanied by significant changes in either plasma or cerebrospinal fluid (CSF) sodium or potassium levels in either SHR or WKY. 3H-Norepinephrine release induced by 56 mmol/l KCl was not altered in either SHR or WKY. However, the ability of yohimbine to enhance 3H-norepinephrine release in caudal artery preparations was significantly decreased by potassium supplementation in SHR, but was not affected in WKY. These data suggest that potassium supplementation may alter alpha 2-adrenoceptor activity. Further studies are required to determine if this altered alpha 2-adrenoceptor activity plays a direct role in the blood-pressure-lowering effects of potassium supplementation. PMID- 2263673 TI - Effect of dopamine beta-hydroxylase inhibition on systemic hemodynamics in conscious, spontaneously hypertensive rats. AB - The acute and chronic effects of a potent and selective dopamine beta-hydroxylase inhibitor, SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol], on systemic hemodynamic variables were assessed in chronically instrumented spontaneously hypertensive and normotensive Wistar rats. The changes observed in the hypertensive rats were compared with those obtained by vehicle in a different group of rats. Following intragastric administration of SK&F 102698 (75 mg/kg), blood pressure and cardiac output decreased gradually in both strains of rats, while total peripheral vascular resistance remained unchanged. The antihypertensive effect of repeated daily administration of SK&F 102698 in the hypertensive rats was sustained for the duration of treatment. During the acute phase, the decrease in cardiac output was due to bradycardia. In addition, as a result of hemodynamic changes, SK&F 102698 significantly reduced the minute work output of the heart. The results indicate that SK&F 102698 lowers blood pressure primarily by decreasing cardiac output. PMID- 2263674 TI - Influence of acute and chronic ethanol administration on the vasopressor effect of serotonin in pithed rats. AB - In pithed rats, the intravenous administration of serotonin (3, 10, 30, 100, 300 and 1,000 micrograms/kg) produced a dose-dependent increase in blood pressure. This action of 5-HT was not changed by chronic ethanol intoxication (6.0 g/kg/day for 2 weeks). The pressor responses to serotonin were, in a dose-dependent manner, significantly reduced by acute ethanol administration (0.5, 1.0, 2.0 and 4.0 g/kg p.o.) and by ketanserin injection (0.03 mg/kg i.v.). However, ethanol (2.0 g/kg) did not amplify the dilator effect of serotonin in pithed rats pretreated with ketanserin (3.0 mg/kg i.v.). We also demonstrated that, in contrast to ketanserin (10(-7) mol/l), ethanol (0.05 mol/l) potentiated the serotonin-induced vasoconstriction of isolated rat tail arteries. These data suggest that the action of ethanol on the vasopressor effect of serotonin in pithed rats does not depend on its influence on serotonergic receptors in blood vessels. PMID- 2263675 TI - Biology and chemistry of active natural substances. International symposium. Bonn, July 17-22, 1990. Proceedings. PMID- 2263676 TI - Assessment of interpersonal problem-solving skills. AB - A new instrument for assessing social skills of schizophrenic patients, Assessment of Interpersonal Problem-Solving Skills (AIPSS), is a videotaped-based test with an examiner's administration and scoring manual. The test measures an examinee's ability to describe an interpersonal social problem, to derive a solution to the problem, and to enact a solution in a role-played simulation test. In a study using a sample of schizophrenic outpatients and a comparison group of nonpatients, we found that the test had adequate psychometric properties, and the patients demonstrated deficits on all scales relative to the nonpatients. The results of the study also provided partial support for the validity of an information-processing model of social skills, which was used as a basis for constructing the AIPSS. Thus, the AIPSS represents a departure from previous methods of assessing social skills. PMID- 2263678 TI - Difficult patients in extended psychiatric hospitalization: a research perspective on the patient, staff and team. AB - A series of publications has emerged from a comprehensive research project on difficulties in extended psychiatric hospital treatment, each of which describes factors that may influence difficulty: staff perceptions, difficult patient profiles, countertransference, intrapsychic features, organic brain impairment, problematic areas of treatment. This paper is intended to provide an overview and clinical integration of those diverse findings and an application of the findings to clinical conceptualization. The research supplements existing knowledge about treatment difficulty and countertransference in dyads by providing information about how such phenomena are influenced by clinical teams, by professional roles or disciplines, and by the treatment delivery system. Finally, I will describe future issues, questions and research efforts that are generated by these findings. PMID- 2263677 TI - Social skills and relapse history in outpatient schizophrenics. AB - Persons with schizophrenia commonly have impaired social functioning (Wallace 1984). Those with greater impairments, particularly as measured by premorbid social attainment, have a poorer clinical prognosis (Strauss and Carpenter 1972). Interventions designed to improve social competence, such as social skills training, have yielded generalizable and durable effects and may have reduced relapse rates (Wallace and Liberman 1985; Liberman et al. 1986; Hogarty et al. 1986). Thus, a valid measure of social skills should be a useful clinical and research tool. This research explores the validity of a new instrument for measuring such skills, the Assessment of Interpersonal Problem Solving Skills (AIPSS) (Donahoe et al., this issue). The AIPSS differs from more conventional social functioning measures because it 1) utilizes observations of role-playing, rather than self-report or third-party report; 2) provides a rating of the patient's current rather than past functioning; 3) involves videotaped simulated "real life" situations that pose challenges to the patient's ability to solve socially relevant problems; 4) permits assessment of patient's social perception, processing of social information for action planning, and verbal and nonverbal social responses. In this study, we examined the relationship between these parameters of schizophrenic patients' social functioning and their recent relapse history. PMID- 2263679 TI - Role of reassurance and psychopathology in hypochondriasis. AB - Patients with hypochondriasis are usually considered unresponsive to medical reassurance, so that a possible therapeutic use of reassurance in hypochondriasis is too often overlooked. This paper examines medical reassurance as an important aspect of an interaction between the patient and physician, and presents specific features of the relationship between the hypochondriacal patient and his psychiatrist in the light of the patient's reactions to attempted reassurance. Response to medical reassurance may provide important clues for the more precise diagnostic assessment of patients with hypochondriasis; it is particularly important to identify those patients who have a strong underlying need for acceptance, because adequate and repeated reassurance has a therapeutic value for them. PMID- 2263680 TI - A critical analysis of the co-dependence construct. AB - Co-dependence is a diagnostic term that has gained increasing usage in clinical and self-help settings. While it is used to encompass a broad range of clinical phenomena, it generally refers to an identity, particularly common among women, based on caretaking and excessive responsibility for others. This paper explores the clinical implications of the co-dependence construct from both social psychological and psychodynamic perspectives. PMID- 2263681 TI - Treatment of premenstrual syndromes with progesterone antagonists (e.g., RU-486): political and methodological issues. AB - The effect of political and social considerations on development and availability of medication is exemplified by the debate of the progesterone antagonist RU-486 and its indications. Premenstrual syndromes (PMS) are quite prevalent. In some women they are severe enough to warrant treatment, but at present there is no single treatment modality that has been shown to be effective with most women with PMS. Increased levels of progesterone and/or its fluctuations during the luteal phase have been suggested as possible factors in the pathophysiology of PMS. Therefore, progesterone antagonists represent a very promising avenue for treatment of a subgroup of PMS, and some other hormonally-related dysphoric disorders as well. Regretfully, because of the abortant properties of these compounds, they are the subject of a fierce debate and political considerations in the United States, and their availability for treatment trials of other indications in women is limited. It is hoped that progesterone antagonists will eventually be introduced for studies of their treatment and efficacy when indicated. PMID- 2263682 TI - Construction of a multidimensional scale of job satisfaction. AB - A comprehensive, multidimensional scale measuring job satisfaction was constructed for use in a major project concerned with personnel recruitment and retention of health professionals. 11 dimensions relating to opinions of immediate supervisors, physical working conditions, satisfaction with coworkers and with pay, aspects related to promotion and work motivation, are identified. These dimensions are shown to distinguish among health professionals on sex and between locations and different occupations. The scale also has high internal validity, producing a multiple R of .78 with over-all job satisfaction. PMID- 2263683 TI - Type A behavior, hardiness, and psychological well-being in Japanese women. AB - The effects of Type A behavior and hardiness on depression and physical symptoms in the face of hassles were examined in 107 Japanese female college students. Analysis of variance indicated that Type A females had less depression under low hassles. There were no hardiness main effects or interactions. Neither Type A behavior nor hardiness moderated the adverse effect of hassles for Japanese women. An implication for research is suggested. PMID- 2263684 TI - Anxiety and blood pressure prior to dental treatment. AB - In the present study dental anxiety and blood pressure were assessed immediately prior to a dental appointment to assess the relationship between self-reported dental anxiety and blood pressure. Blood pressure was assessed by two independent methods, and the interchangeability of the blood-pressure measurement methods was also assessed. No relationship was demonstrated among scores on three dental anxiety questionnaires and blood-pressure values. The blood-pressure measurement methods delivered comparable values for diastolic and mean arterial blood pressure only. PMID- 2263685 TI - Similarity among common measures of academic achievement: implications for assessing disabled children. AB - Four commonly used measures of academic achievement were administered in counterbalanced order to 32 elementary and middle school-aged children enrolled in exceptional education programs for the learning disabled. Measures chosen were the Kaufman Test of Educational Achievement, KeyMath-R, Test of Written Spelling 2, and the Gray Oral Reading Test-Revised. Analysis suggested corresponding measures of reading, mathematics, and spelling were highly correlated, although in some instances generated significantly different mean standard scores. Implications for practitioners are discussed. PMID- 2263686 TI - Preliminary study of the relationship between guilt resolution and depression in a gerontological population. AB - An individual interview process was used to investigate the relationship between proneness to depression in a gerontological sample and their evaluation of critical life incidents. High and low depressed individuals were asked to recall prideful and guiltful incidents from their past, and discrepancy scores were obtained between their past and present evaluations of those events. Limited evidence supported the hypothesis that individuals with higher proneness to depression showed a greater negative discrepancy in evaluations of critical life incidents. Subjects did not differ in the content of their recalled incidents as a function of guilt type or guilt referent. PMID- 2263687 TI - Countertransference in the movies: effects on beliefs about psychiatric treatment. AB - This study examined the effect of viewing the movie Lovesick on college students' beliefs about countertransference and psychiatric practice. Consistent with the concerns of Gebbard and Gebbard (1985) that the public may develop erroneous beliefs about psychiatry from watching such movies, after seeing the film subjects were more accepting of sexual behavior between analyst and patient and were cynical about the motivation of the mental health professions in prohibiting such behavior. PMID- 2263688 TI - Self-monitoring, depression and suicidal ideation. PMID- 2263689 TI - Information search following damage to the frontal lobes. AB - Five adult patients with focal brain damage in different areas of the frontal lobes and five matched controls were administered a 20 Questions test. Other tests of planning, problem-solving, and decision-making were also administered to frontal lobe patients. The results indicate that damage to the frontal lobe impairs the ability to impose and utilize hierarchical organization in mental representation. PMID- 2263690 TI - Left-handedness: association with college major, familial sinistrality, allergies, and asthma. AB - 366 juniors, seniors, and graduate students from seven departments at The Ohio State University were administered the 10-item Edinburgh Handedness Inventory and asked questions concerning familial handedness and personal incidence of allergies or asthma. The rate of left-handedness was 15.6% among the male students and 12.9% among the females. Maternal handedness was significantly related to female offspring handedness and to the incidence of allergies and asthma in both males and females. Departmental incidence of left-handedness ranged from a low of 7.5% (Microbiology) to a high of 21.7% (Law). PMID- 2263691 TI - Emotional impact on trail making test performance. AB - This study assessed the effect of emotional factors on Trail Making Test Part B performance for a sample of 105 neuropsychological referrals for whom there was no neurodiagnostic evidence of brain damage. Trails B scores declined in relation to elevated MMPI scores on Scales 6, 7, and 8, though only nine patients performed within the impaired range. The results suggest that (a) Trails B performance is resilient to a variety of emotional influences, (b) psychotic symptoms and severe anxiety impede Trails B performance, though rarely to the extent caused by brain damage, and (c) the MMPI provides objective criteria that help rule out emotional effects on Trails B performance. PMID- 2263692 TI - Exploring the reinforcement of compliance with "do" and "don't" requests and the side effects: a partial replication and extension. AB - The side effects of reinforcing compliance to "do" and "don't" requests were examined in this study. The study was designed to do two things: (1) further establish that "do" and "don't" requests are functionally distinct and (2) determine which "don't" requests will show the same ability as "do" requests in effecting a change in topographically different inappropriate behaviors. Three children (2 boys and 1 girl), ages 5 yr. 2 mo. to 6 yr. 7 mo., participated. The design of the study was ABAC counterbalanced across subjects. With all three children reinforcement of "do" requests led to increased compliance with "do" requests without concurrent increase in compliance to "don't" requests. Also, reinforcing compliance to "don't" requests resulted in increased compliance to "don't" requests without concurrent increase in compliance to "do" requests. An undesirable side effect to the treatment was also noted. Two children showed a tendency to increase their rates of inappropriate behavior concurrent with increases in compliance to "don't" requests. Probable causes for this effect and concerns about the reinforcement of "don't" requests were discussed. PMID- 2263693 TI - Body attitudes and eating behaviors of female clothing sales personnel. AB - Recent research suggests that social standards for ideal female beauty are related to negative body-image and dieting among young women. We hypothesized that women who work in settings that emphasize physical appearance (women's fashion clothing sales) would have more disturbed body attitudes and eating behaviors than college women. Sales personnel (n = 21) and students (n = 25) answered questions about their occupational status, weight, and demographic characteristics, and completed the Body-esteem Scale and the Eating Disorder Inventory. Weight and scores on the two scales were similar in both groups except that sales personnel reported more dissatisfaction with their body parts on the Body dissatisfaction scale of the Eating Disorder Inventory. Among sales personnel, those who perceived their appearance to be of greater importance in their work also reported more concern about dieting and weight, as reflected on the Drive for thinness subscale of the Eating Disorder Inventory. Results are discussed with regard to situational influences on women's body attitudes and their implications for eating behaviors. PMID- 2263694 TI - Relationship between egocentrism, alcohol consumption and reasons given for drinking. AB - University students, 86 men and 141 women, completed a questionnaire from which their level of egocentrism, amount of alcohol consumed, and number of reasons for drinking could be estimated. Analysis supported earlier findings that men consume significantly more alcohol than do women. Both men and women who were rated as having high egocentrism scores gave significantly more reasons for drinking than did the women scoring low on egocentrism. Also, there was a significant correlation between egocentrism and reasons for drinking but not between egocentrism and amount consumed. The correlation was higher between the number of reasons given for drinking and the amount of alcohol consumed. Since men scoring high on egocentrism report the highest consumption, while high-scoring women report the lowest consumption, it is concluded that egocentrism plays an indirect role in the consumption of alcohol and the role it plays is different for men and women. PMID- 2263695 TI - Self-actualization of gifted youth as measured on the reflections of self by youth. AB - The self-actualization of 74 intellectually gifted youth in Grades 4 through 8 was studied through the administration and data analysis of Reflections of Self by Youth. Scores for boys and girls were similar and more like those of bright youth of a prior study than like those of the subjects of normal intelligence. PMID- 2263696 TI - Temporal stability of a safety attitude inventory. AB - The purpose of this study was to examine the temporal stability of a paper-and pencil inventory on safety attitudes, the Employee Safety Inventory. 62 employees of a major publishing company completed the inventory twice with a 10-day interval between testings. A test-retest reliability coefficient of .88 was obtained for the over-all Safety Index. No significant differences in reliability coefficients were found between men and women or between those who had experienced major life events during the time between testings and those who had not experienced such events. This inventory provided a highly reliable measure of safety attitudes. PMID- 2263697 TI - The supervisory relationship in psychotherapy over time. AB - This study investigated changes in the supervisors' and supervisees' perceptions of the supervisory relationship and the extent to which their perceptions were congruent. Salient dimensions of supervision were identified which predict the quality of the relationship. Twelve supervisory dyads involved in predominantly ongoing supervisory relationships completed an adapted Vanderbilt Psychotherapy Process Scale after each supervisory session for 10 consecutive weeks. The participants' perceptions of the supervisory relationships were relatively stable and positive. However, supervisees felt less dependent over time. With that exception, agreement among participants did not change significantly. Supervisors viewed supervisees' participation and increased assertiveness as significant positive elements in assessing the quality of the relationship. Supervisees' greater exploration and dependency was associated with negative ratings by supervisors. Since supervisors selected the supervisees for the study, the results primarily validate their judgments of the components of a positive continuing supervisory relationship. PMID- 2263698 TI - Psychiatric disorders and motor vehicle accidents. AB - The literature has often suggested a relationship between psychiatric illness and increased risk for motor vehicle accidents but few data exist, particularly those from prospective or case-controlled studies. The present study examined detailed accident and injury data from a large series (N = 1778) of motor vehicle crashes that included persons with diagnoses of psychiatric illnesses (n = 17); matched controls were also studied. As expected, drivers with psychiatric diagnoses used psychotropic medications more frequently than did controls. Drivers with psychiatric diagnoses did not have more frequent single-car crashes, unsafe speed or failure to yield violations, or less restraint use than did controls. Such drivers did less often drive motorcycles and tended to be less often cited for alcohol use. Implications of these results for efforts toward prevention and for further study are discussed. PMID- 2263699 TI - Relationship between firearm availability and primary and secondary murder. PMID- 2263700 TI - Attitudes of nursing students toward patients with AIDS. AB - Nursing students (N = 124) voluntarily completed a questionnaire designed to measure attitudes towards patients with AIDS. The questionnaire included one of two vignettes, a prejudicial evaluation scale, and the Index of Homophobia. Results indicate that nursing students expressed a significantly more negative attitude toward the homosexual patients with AIDS. Homophobia accounted for a substantial amount of variation in the difference in expressed attitude between heterosexual and homosexual AIDS patients. The researchers recommend that nursing students and other prospective health care workers be provided educational programs dealing with AIDS which include study of homophobia and homosexuality. PMID- 2263701 TI - A study of opportunity-based suicide rates: the use of guns. PMID- 2263702 TI - Update on the parallel analysis criterion for determining the number of principal components. AB - Recent developments in parallel analysis with unities in the diagonal are reviewed, and the application of the parallel analysis criterion is illustrated with three examples. It is shown that the results of various approaches do not always agree. Investigators are encouraged to employ the parallel analysis criterion, along with one or more other criteria, in deciding on the number of principal components. PMID- 2263703 TI - Personality correlates of anxiety about public speaking. AB - McCroskey (1982) has hypothesized that there are various forms of apprehension about communication some of which are situation specific and some of which are best thought of as traits. Other research has established a relationship between personality variables and a trait conception of apprehension about communication. If McCroskey's distinction between trait and situation-based state is appropriate, personality variables ordinarily associated with trait apprehension about communication should not correlate as highly with forms defined as more situation specific, such as anxiety about public speaking. Multiple regressions were performed using trait measures of apprehension about communication (the Personal Report of Communication Apprehension) and situation-based anxiety (the public speaking factor of the Personal Report of Communication Apprehension) as dependent variables. As hypothesized, contributions of personality were less for trait than situation-specific apprehension about communication. The inclusion of self-monitoring as a moderator variable added additional information about the contributions of personality to situation-specific apprehension about communication, with personality being more predictive of apprehension about public speaking for low self-monitors. PMID- 2263704 TI - Relationship of age and sex-role conflict for professional women in human services. AB - This study provides external validation of the Sex-role Conflict Scale. The relationship between age and sex-role conflict among women with educational interests was investigated. 128 female students in education were assessed on the conflict they experienced in various settings. The mean sex-role conflict scores, although hypothesized to be significantly different, were not among women ages 25 yr. and below, ages 26 to 39 yr., and ages 40 yr. and over. Also investigated was the relationship between age and sex-role conflict in dual-career respondents. Of the 29 respondents who met the criterion for classification, mean sex-role conflict scores were not significantly different for the three age groups. The nonlinear relationship between sex-role conflict and age does not have support for professional women who work in fields other than business. PMID- 2263705 TI - The validity of the mu index for differentiation of state and trait scales. AB - For 443 men and women of the general population and mean age of 45.8 yr. state and trait measures were obtained on two occasions, 6 mo. apart. Internal consistencies at each time were similar (.84-.95). Test-retest coefficients were lower for measures of state concepts than for trait concepts. Howarth's mu indices were higher for state concepts than for trait concepts. PMID- 2263707 TI - A multidimensional approach for selecting child care workers. AB - A multidimensional selection battery was designed to predict a variety of criteria important in the selection of child care workers. The battery assesses constructs related to honesty, violence, substance abuse, emotional stability and safety. A series of studies were used to test the validity of the selection battery. Scores on the test battery were compared with those from three alternative selection procedures to define the measured constructs. Three additional studies show the relation of scores on the selection battery and the behavior of child care workers. The test battery was correlated with the job performance of child care workers and identified adults convicted for sexual offenses against minors. PMID- 2263706 TI - Report on Shanghai norms for the Chinese translation of the Wechsler Intelligence Scale for Children-Revised. AB - The Chinese translation of the Wechsler Intelligence Scale for Children--Revised (WISC-RC) was administered to 660 children (ages 6 through 16 yr.) in the city of Shanghai. The obtained norms represent children's intelligence levels in big cities where the economic and cultural development is advanced. The norms are reported as "Scaled Score Equivalents of Raw Scores" for each age group and as "IQ Equivalents of Sums of Scaled Scores." The reliability and validity of the norms indicate that the WISC-R is suitable for use with school-age children in China. The difference between the results for our Shanghai sample (WISC-RCs) and a USA sample (WISC-R) is also discussed. PMID- 2263708 TI - Stability and concurrent validity of the PPVT-R in hospitalized psychotic adolescents. PMID- 2263709 TI - A psychometric investigation of the Rigorous Eating Scale. AB - A psychometric analysis of the Rigorous Eating Scale was carried out based on data of Smead from 1986 and also from 1987 by Smead and Boyd. This 13-item scale was designed to measure hunger, deprivation, and restraint in eating style and used in both of the foregoing studies to investigate the relationship between dieting and eating style and scoring higher on measures of subclinical symptoms of anorexia and bulimia. This brief report highlights internal consistency reliability, factor structure, and item-criterion correlations. Results indicate appropriately high reliability, but inadequate factor structure. Item-criterion correlations suggest several aspects of eating style which may be important to include in similar scales of the future. PMID- 2263710 TI - Relationships among defensive styles, cognitive styles, processing styles, and attentional styles of normal adolescents. AB - Cognitive and psychodynamic theorists agree that an individual's personality and behavior are determined by both cognitive and dynamic processes. This study examined the relationship among three cognitive approaches--cognitive style, attentional style, and processing style--and examined their relations to defensive style. Adolescents from Grades 11 and 12 (146 boys, 164 girls) were examined in groups for cognitive style (Group Embedded Figures Test), attentional style (Test of Attentional and Interpersonal Style), processing style (a sequential/simultaneous processing test battery), and defensive style (Defense Mechanism Inventory). Least squares completely randomized two-way analyses of variance (or analyses of covariance where applicable) were employed to assess the relations among the three cognitive measures and/or between the cognitive measures and defensive style. While most comparisons were nonsignificant, a significant relationship was observed between sequential processing and field dependence and between simultaneous processing and field-independence. Also, a trend was noted between field-independence and ideational defenses and between field-dependence and repression-based defenses. PMID- 2263711 TI - Effect of response effort with reward for leverpress or release. PMID- 2263712 TI - Relationships among measures of alcohol drinking behavior, life-events and perceived stress. AB - Two measures of stress (life-events and perceived stress) and a measure of alcohol-drinking behavior were administered to 6,747 adult males. Analysis was carried out to examine the extent to which subjects classified into drinking behavior groups differed on stress measures while controlling for age, income, and race. Significant differences held up under age, race, and income controls for life-events and perceived stress between the abstinence, common-use, and problem-drinking groups. Stress scores increased sequentially across the drinking behavior groups. Apparently, men who are life-long abstainers (teetotallers) experience fewer life-events and perceive less stress than moderate drinkers, while moderate drinkers experience less stress than heavy drinkers. PMID- 2263713 TI - Comparison of the Kaufman Assessment Battery for Children (Achievement Scale) and the Basic Achievement Skills Individual Screener for learning disabled students. AB - The Kaufman Assessment Battery for Children--Achievement Scale and Basic Achievement Skills Individual Screener were administered to 40 students previously identified as learning disabled. Pearson coefficients between the sets of scores on various subtests ranged from .03 to .70. PMID- 2263714 TI - Comparison of characteristics of Vietnam veterans with and without posttraumatic stress disorder. AB - Characteristics of 107 Vietnam veterans with and without Posttraumatic Stress Disorder (PTSD), who had been exposed to varying levels of combat, were compared. Severity of psychopathology as assessed on the Eysenck Personality Questionnaire, locus of control orientation as measured by the Nowicki-Strickland Internal External Control Scale, and ability to have provided structure and meaning to the Vietnam experience were examined. Compared to veterans with Posttraumatic Stress Disorder, those without the disorder had lower Neuroticism and Psychoticism scores, were more internal in their locus of control orientation, and were more likely to have shown ability to provide structure to the Vietnam experience. The additional finding that veterans with high combat experience but without PTSD evidenced less neuroticism than low combat veterans without PTSD provides evidence that those who did not develop the disorder despite high exposure to combat stress are individuals with exceptional emotional strength and resilience. PMID- 2263715 TI - Barbadian adolescents' views of the "ideal" family. AB - An instrument examining the perceptions of "ideal" family functioning was administered to 536 adolescents aged 12 to 18 yr. in Barbados. Analysis indicated fairly extensive differences between the views of male and female students, somewhat fewer differences in age and type of school attended, and very few differences associated with household composition and religious affiliation. PMID- 2263716 TI - Athletic self-concept and mathematics achievement in girls. AB - Several researchers have suggested that girls' mathematics performance may be mediated by an assertive sex role or "masculine interest." The present study made the assumption that girls' athletic self-confidence reflects "masculine interest" so girls' test scores for perceived athletic competence would be related to their mathematics achievement scores. A total of 207 boys and girls in Grades 4, 5, and 6 were tested for their perceived athletic ability using the Athletic Competence subscale of Harter's 1985 Self-perception Profile, and these scores were correlated with their mathematics achievement as measured on the Metropolitan Achievement Test and term grades. A low but significant correlation with Athletic Competence scores was found for girls on both measures of mathematics achievement. Although boys scored higher on the Athletic Competence subscale, there were no sex differences on either measure of mathematics achievement. Results are discussed in terms of both sex-role theory and cognitive development. PMID- 2263717 TI - Immunization against learned helplessness in the cockroach (Periplaneta americana). AB - Cockroaches exposed to one day of escapable shock prior to three days of inescapable shock did not become helpless on a shuttlebox-escape task. Like dogs and rats, cockroaches are immunized against learned helplessness by prior experience with escapable shock. PMID- 2263718 TI - Effects of alcohol on prolonged cognitive performance measured with Stroop's Color Word Test. AB - 24 men and 24 women were randomly assigned in equal numbers to an Alcohol group, a Placebo group, or a Control group. The alcohol dose was 1.0 ml of 100% alcohol/kg of body weight. Subjects were tested three consecutive times using Stroop's Color Word Test. The dependent measures were total time needed to complete the test, number of errors made and number of hesitations. Data were grouped into three blocks of 100 words. Results indicated that number of hesitations was too insensitive a measure to yield any significant effects. On the two first measures alcohol had a detrimental effect in that the Alcohol group needed more time to complete the test and made more errors than the Placebo group. There was also a significant interaction of alcohol dose by sex by blocks on both these measures, indicating that the detrimental effect of alcohol over time was restricted to women. Different implications of the results were discussed. PMID- 2263719 TI - Distress and performance appraisal satisfaction. AB - 120 quality assurance engineers indicated how frequently job stressors, causing distress related to role ambiguity, role conflict, role overload, and career development, affected them at work. They also indicated their satisfaction with their most recent performance appraisal. Satisfaction with performance appraisal was significantly negatively correlated with each stressor. PMID- 2263721 TI - Accountancy, teaching methods, sex, and American College Test scores. AB - This study examines the significance of sex, methodology, academic preparation, and age as related to development of judgmental and problem-solving skills. Sex, American College Test (ACT) Mathematics scores, Composite ACT scores, grades in course work, grade point average (GPA), and age were used in studying the effects of teaching method on 96 students' ability to analyze data in financial statements. Results reflect positively on accounting students compared to the general college population and the women students in particular. PMID- 2263720 TI - Development of covert and overt hostility scales from the Buss-Durkee Inventory. AB - The purpose of this study was to develop covert and overt hostility scales from the Buss-Durkee Inventory. First, 22 covert hostility and 29 overt hostility items were identified by the authors. Second, an item analysis was done to assess the content saturation of the individual items on these scales. This analysis yielded the final form for 7 items for covert hostility and 14 for overt hostility. Cronbach alphas for the covert and overt scales were .67 and .77, respectively, and their intercorrelation was .08. Correlations for these Buss Durkee scales with several existing measures of anger expression were consistent with expectations. PMID- 2263722 TI - Self-concepts of creative girls: a twenty-five year follow-up. AB - The 25-yr. follow-up study of the self-concepts of a highly creative group of 10 adolescent girls showed both stability and change. In mid-life the group continued to describe themselves as both creative and intelligent; however, they also changed in that they now regard themselves as having a greater social interest. PMID- 2263723 TI - Learning disabilities: an appraisal of Rorschach response patterns. AB - Recent developments with the Rorschach invite research concerning cognitive and coping styles of learning disabled students. This study, based on an N of 25 (12 learning disabled and 13 controls), was designed to assess group differences in perceptual accuracy, self-concept, and reactivity. Analysis showed that learning disabled students represent a diverse population for which highly individualized understanding is required if appropriate schooling strategies are to be devised. Such students, compared with controls, were more inclined to have lower self confidence, to be more reactive, to avoid emotionally-laden stimuli, to manifest a higher proportion of responses involving perceptual inaccuracies, and to be less spontaneous and less inclined to take risks. Some curricular implications of the findings are discussed. PMID- 2263724 TI - Frequency and duration of therapeutic intervention with young children with cerebral palsy. AB - Though the terms 'frequency' and 'duration' of physical and occupational therapy strategies for young children with cerebral palsy are inextricably woven, little research has been done to support the provision of these therapies. More recent studies have implied the expanded role of therapists in providing and participating in nontraditional types of intervention. An argument is presented for this position. PMID- 2263725 TI - Iododeoxyuridine radiosensitization by low- and high-energy photons for brachytherapy dose rates. AB - The dependence of iododeoxyuridine (IUdR) radiosensitization on photon energy and dose rate in the range of interest to brachytherapy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions. The radiosensitization produced by 10(-5) and 10(-4) M IUdR for 28-keV (average) photons from 125I, 60-keV photons from 241Am, and 830-keV (average) photons from 226Ra was measured at nominal dose rates of 0.17, 0.30, 0.57, and 0.73 Gy/h. Radiosensitization factors for IUdR were essentially independent of dose rate from 0.30 to 0.73 Gy/h for all cases except for 10(-4) M IUdR plus 241Am, in which case the radiosensitization factor increased from 2.5 +/- 0.2 to 3.0 +/- 0.1. In all cases, the radiosensitization factor decreased significantly as the dose rate was lowered from 0.30 to 0.17 Gy/h e.g., the radiosensitization factor for 241Am dropped to 1.9 +/- 0.2 at a dose rate of 0.17 Gy/h. Moreover, at 0.17 Gy/h the radiosensitization factors were essentially the same for all three photon energies. As the dose rate increased from 0.17 to 0.73 Gy/h, the difference between the radiosensitization factors for the three photon energies became larger; radiosensitization factors for 241Am were higher than those for 226Ra and 125I. In temporary brachytherapy the tumor is irradiated at the higher dose rate of about 0.50-0.70 Gy/h, while the normal tissues are irradiated at lower dose rates; the dose rate dependence of the radiosensitization factor may therefore lead to an improvement in the therapeutic ratio for brachytherapy in combination with IUdR. PMID- 2263726 TI - The dependence of thiol-inducible radiation resistance in Escherichia coli K12 on the medium and catalytic metal. AB - Radiation protection by thiols in procaryotes and lower eucaryotes has been demonstrated repeatedly to require a competent DNA repair phenotype, suggesting that simple chemical radical scavenging and hydrogen donation are only a portion of the mechanism of radiation protection by thiols. In the present report, thiol induced radiation resistance--a model in which cells are pretreated with dithiothreitol and then irradiated in the absence of thiol--is shown to be a medium-dependent process. Wild-type log-phase cells treated with dithiothreitol in minimal-glucose medium are induced to radioresistance that persists after the thiol has been removed. Although the thiol pretreatment affected the antioxidants (catalase, superoxide dismutase, and glutathione) in cells at the time of irradiation, various antioxidant levels did not predict radiation resistance. Thiol-induced radioresistance is not expressed in rich medium-treated cells or in DNA repair (recA)-deficient cells. Addition of the efficient chelator, DETAPAC, to the thiol treatment medium leads to additional radioresistance in the case of minimal medium and a moderate expression of resistance in rich medium. Experiments using the intracellular chelator, 1,10-phenanthroline, in the presence of thiol led to inhibition of thiol-induced resistance in minimal medium and radiosensitization in rich medium. These results can be explained by a "site specific" mechanism of thiol oxidation in which the chelators control the site(s) and rate of thiol oxidation, subsequently determining the type of cellular response. PMID- 2263728 TI - A comparison of the radiation response of the epidermis in two strains of pig. AB - The response of the epidermis was compared in two strains of pig, the English Large White and the Gottinger Miniature, after irradiation with 90Sr beta rays. The effects of two types of anesthesia were also tested in pigs of each strain, a volatile gas mixture of approximately 70% oxygen, approximately 30% nitrous oxide, and 2% halothane, and an intravenously administered narcotic azaperon/etimodat with the animals breathing air. Strain- and anesthetic-related changes were compared on the basis of dose-effect curves for the incidence of moist desquamation from which ED50 values (+/- SE) were determined, i.e., the dose required to produce this effect in 50% of the fields irradiated. For English Large White pigs anesthetized with the volatile gas mixture, an ED50 of 27.32 +/- 0.52 Gy was obtained for moist desquamation. Irradiation with the azaperon/etomidat anesthesia in this strain of pig produced a significantly higher ED50 of 33.36 +/- 0.76 Gy (P less than 0.001). This appeared to be related to the fact that the animals were breathing air, i.e., a lower oxygen concentration (approximately 21%), at the time of irradiation. For the Gottinger Miniature pig the ED50 values for moist desquamation were 38.93 +/- 3.12 Gy and 43.36 +/- 1.34 Gy while using the gaseous anesthetic mixture and the azaperon/etomidat anesthesia with the animals breathing air, respectively. These ED50 values are 10-11 Gy higher than those obtained for the English Large White pig under identical conditions of anesthesia, which resulted in a strain difference ratio of approximately 1.35. Radiation under the volatile gas mixture anesthesia resulted in a uniform irradiation response over the skin of the flank in both strains of pig. Radiation under azaperon/etomidat anesthesia resulted in a nonuniform skin response over the flank. The ED50 for moist desquamation was significantly higher in dorsal sites on the flank compared with the ventral area of English Large White pigs; a similar trend was seen in Gottinger Miniature pigs. This difference in the radiosensitivity over the flank skin while the animals are under azaperon/etomidat anesthesia at the time of irradiation was associated with the animals breathing air and is in agreement with findings published previously for animals under halothane anesthesia and breathing air. PMID- 2263727 TI - How well is the probability of tumor cure after fractionated irradiation described by Poisson statistics? AB - The probability of tumor cure in a homogeneous population of tumors exposed to fractionated radiotherapy was modeled using numerical simulations and compared with the predictions of Poisson statistics, assuming exact knowledge of the relevant tumor parameters (clonogen number, radiosensitivity, and growth kinetics). The results show that although Poisson statistics (based on exact knowledge of all parameters) accurately describes the probability of tumor cure when no proliferation occurs during treatment, it underestimates the cure rate when proliferation does occur. In practice, however, the inaccuracy is not likely to be more than about 10%. When the tumor parameters are unknown and are estimated by fitting an empirical Poisson model to tumor-cure data from a homogeneous population of proliferative tumors, the resulting estimates of tumor growth rate and radiosensitivity accurately reflect the true values, but the estimate of initial clonogen number is biased downward. A new formula that is more accurate than Poisson statistics in predicting the probability of tumor cure when proliferation occurs during treatment is discussed. PMID- 2263729 TI - Inverse dose-rate effect for the induction of 6-thioguanine-resistant mutants in Chinese hamster V79-S cells by 60Co gamma rays. AB - Chinese hamster V79-S cells capable of growing in suspension culture were exposed to 60Co gamma rays at a high dose rate (84 Gy/h), low dose rates (200, 50, and 39 mGy/h), and a spectrum of very low dose rates (between 29 and 4.5 mGy/h). Following time for appropriate expression the cultures were assayed for the induction of 6-thioguanine-resistant mutants. For a given dose, a decrease in mutation induction occurred as the dose rate was reduced from high dose rates to low dose rates. However, further reduction in dose rate resulted in a reverse dose-rate effect, and an increase in the frequency of mutants was observed. The contribution of background mutation frequency to this reverse dose-rate effect was studied, both by examining fluctuations of mutation frequency in nonirradiated culture and by its impact upon the dose-rate-independent nature of the reversed effect, and it was found to be negligible. The physiological state of the suspension culture under periods of protracted exposure to very low dose rates was also investigated. The effect of doubling time, plating efficiency, cell cycle distribution, and sensitivity on survival and mutation were examined. In no case was a change apparent during the very low-dose-rate exposures. The results are discussed in terms of the possible expression of cryptic radiation damage after prolonged culture times and/or the involvement of an error-free repair system which requires a certain amount of radiation damage to become active. PMID- 2263730 TI - Detection of ionizing radiation-induced DNA double-strand breaks by filter elution is affected by nuclear chromatin structure. AB - Chinese hamster ovary cells were irradiated with 250 kVp X rays and analyzed for the presence of DNA double-strand breaks using either polycarbonate filter elution or pulsed-field agarose gel electrophoresis at neutral pH. Reduction in DNA length detected by filter elution was produced as a nonlinear function of increasing radiation dose, with a quasi-threshold at low total dose, and as a first-order function of increasing radiation dose as detected by gel electrophoresis. The quasi-threshold observed with filter elution was eliminated when nuclei were isolated from irradiated cells and their chromatin relaxed in a buffer containing low-molarity monovalent cation prior to analysis by filter elution. The results suggest either that the chemical structure of the DNA double strand breaks produced by low-LET radiation necessitates a DNA relaxation step before they can be detected accurately by filter elution, or that at low total radiation dose a DNA complex forms on the polycarbonate filter. PMID- 2263731 TI - Modification of radiation damage in the canine kidney by hyperthermia: a histologic and functional study. AB - The purpose of this study was to evaluate the effect of hyperthermia on the histologic and functional response of the canine kidney, a late-responding normal tissue, to irradiation. Both kidneys were irradiated. Radiation was delivered in single doses of 0, 10, or 15 Gy. Whole-body hyperthermia was used to produce renal kidney temperatures approximating 42.0 degrees C for 60 min. Thirty-six beagles were placed randomly in the following six treatment groups: control, whole-body hyperthermia alone, 10 Gy alone, 10 Gy + whole-body hyperthermia, 15 Gy alone, and 15 Gy + whole-body hyperthermia. Renal histologic and functional changes were assessed at 1 to 9 months after therapy. No changes were seen in glomerular filtration rate or renal tissue volumes in control or hyperthermia alone groups. Renal vascular and glomerular volumes were not affected significantly by any combination of hyperthermia and/or radiation. In all groups receiving radiation, glomerular filtration rate decreased, percentage renal tubular volume decreased, and interstitial volume increased significantly after therapy. The magnitude of these changes in the functional and histologic response of the kidney and the latent period before expression of this damage were dependent on radiation dose. However, hyperthermia did not modify expression of radiation damage in the kidney based on glomerular filtration rate and histologic quantification of renal tissue components. PMID- 2263732 TI - Physical basis for detection of DNA double-strand breaks using neutral filter elution. AB - Results using neutral filter elution are difficult to explain if this method detects only DNA double-strand breaks (DSBs). In an attempt to understand neutral filter elution, the size of DNA pieces eluted from filters was measured using pulsed-field gel electrophoresis. Contrary to expectation, the size of the pieces was independent of radiation dose and time of elution, and much smaller (approximately 460 kb) than anticipated based on the expected number of DSBs induced. Shearing of the DNA molecule, the presence of nonspecific nucleases, and the influence of DNA-associated proteins were examined but could not explain our results. Consequently, we propose that cell lysis causes swelling of the DNA gel, and the exposed fraction of DNA on the surface of the gel is then sheared as the elution solution flows through the filter. We suggest that the rate of DNA elution measured using neutral filter elution is dependent upon the number of DSBs present, the composition of the eluting solution, especially with regard to the presence of molecules which can influence chromatin swelling on the filter, and the conformation or "packaging" of DNA before lysis. PMID- 2263733 TI - A comparison of the induction of DNA double-strand breakage and lethal lesions by X irradiation in ataxia telangiectasia and normal fibroblasts. PMID- 2263734 TI - Ionizing radiation risks: present and future. Proceedings of the American Statistical Association Conference on Radiation and Health. Copper Mountain, Colorado, July 8-12, 1990. PMID- 2263736 TI - The embryonic development of mammalian neural tube defects. PMID- 2263735 TI - Arterial baroreceptor reflex: its central and peripheral neural mechanisms. PMID- 2263738 TI - [Ticks of the Ixodidae family as reservoir of arboviruses in the Republic of Guinea. II. Arboviruses]. AB - From 1978 to 1985, 96,167 Ixodidae family were collected, from which 79 strains of the following arboviruses were isolated, i.e. 4 Bhanja strains, 9 CHF-Congo, 20 Dugbe, 24 Jos (viruses ecologically related to ticks), 10 Abadina, 7 Bluetongue, 1 Bunyamwera, 1 Chikungunya, (related to ticks for the first time), 1 Kindia and 2 Forecariah (new viruses). The main sources for arbovirus isolation were ticks of the Amblyomma variegatum genus (78.5%) followed by ticks of the Boophilus (12.6%), Rhipicephalus (7.6%) and Haemaphysalis (1.3%) genera. According to experimental data obtained in the laboratory and in the field involvement of A. variegatum as reservoir host for Abadina virus was established. The seasonal dynamics characteristics of the propagation of this virus and its pathogenicity for cattle were also noticed. Serological surveys on cattle (i.e. on about 7000 sera) showed that Abadina, Bluetongue, CHF-Congo, Dugbe viruses spread more actively, with 24-35% positive sera. The rate of positive sera against Bhanja, Forecariah, Jos and RVF viruses did not exceed 0.9%. During the study period, the arboviruses isolated from ticks did not play any important epidemiological role in human pathology of the Republic of Guinea. PMID- 2263739 TI - Pathogenicity of attenuated peste des petits ruminants virus in sheep and goats. AB - Progressive loss of virulence for goat kids was noticed when peste des petits ruminants (PPR) virus was passaged in Vero cells. While goats inoculated with the 60th passage suffered from the clinical PPR disease and mortality, goats inoculated with the 80th passage did not show any sign of the disease. If the progressive loss of virulence of the virus with passage continues, it will not be long before a homologous PPR vaccine will be obtained at the National Veterinary Institute, Vom. PMID- 2263737 TI - Circadian rhythm of serotonin binding in rat brain. PMID- 2263740 TI - [Note on goat pox in Chad: study of the foci]. AB - Several outbreaks of goat-pox were observed from 1985 to 1989 in different villages of the N'Djamena area. The virus strain circulating in this region seemed to be host-specific for goats since sheep kept in contact with goats did not suffer from the disease. Nevertheless, it has to be studied further on whether the virus isolated from sick goats could be pathogenic for sheep. PMID- 2263741 TI - Detection of African horsesickness (AHS) in recently vaccinated horses with inactivated vaccine in Qatar. AB - Two 7-year old Arabian racing horses were reported to show typical AHS symptoms in Qatar and died shortly after. The horses had been vaccinated with formol inactivated vaccine approximately 10 days before the onset of the disease. Blood samples from these horses were collected and AHS virus isolated from one sample after intracerebral (i.c.) inoculation into suckling mice. The virus identity was confirmed by complement fixation test (CFT) using the virus antigen and reference type 9 of AHS virus hyperimmune serum. The serotype of the isolated virus was identified by serum neutralization test (SNT) using reference types of AHS virus. Two possibilities of the original source of this infection were suggested. The infection might be due first to the natural endemic occurrence of the virus in the country and secondly, to the presence of residual infectious virus in the inactivated vaccine. PMID- 2263742 TI - [Epidemiologic survey and serodiagnosis of contagious agalactia of small ruminants in Eastern Algeria]. AB - Contagious agalactia is largely present all over the world and affects most of the African countries. It plays an important economic role in terms of subsequent milk and meat losses. One third of the 15 millions of sheep living in Algeria is present in the Eastern regions. A survey was conducted in order to confirm the existence of the disease and to evaluate the prevalence. A total of 372 sera and 80 milk samples was collected from suspected herds i.e. herds presenting either mastitis and arthritis symptoms or mastitis and keratitis symptoms. It was possible using several serological tests to detect the positive animals and to compare the specificity and sensitivity of the tests. PMID- 2263743 TI - Enterotoxigenicity of staphylococci isolated from raw milk obtained from settled and nomadic herds around Zaria, Nigeria. AB - Staphylococcal isolates from 135 raw milk samples obtained from settled herds (42) and nomadic herds (93), were characterized and assayed for enterotoxin production. Of the 42 samples from settled herds, 13 (31%) were California Mastitis Test (CMT)-positive, but all the samples contained staphylococci. Only 3 (3.2%) of the 93 raw milk samples from nomadic herds were CMT-positive but 58 (62.4%) contained staphylococci. Of the 13 isolates from CMT-positive milk obtained from settled herds, one produced enterotoxin A, while amongst the 29 from CMT-positive milk, 4 elaborated enterotoxin A and 3 produced type D. None of the isolates from milk obtained from nomadic herds was enterotoxigenic. PMID- 2263744 TI - Experimental infection of Red Sokoto goats with Salmonella typhimurium. AB - Salmonella typhimurium infection was experimentally induced in goats by administering 2 x 10(10) organisms per os. The disease produced was characterized by pyrexia, diarrhoea and neutrophilia. One goat died from septicaemia. Somatic "0" agglutinins were detected 14 days post infection (p.i.). Excretion of organisms in faeces ceased by 6 weeks p.i. Goats which recovered from primary infection were refractory to a secondary challenge with 2 x 10(11) organisms. The results indicate that in the absence of signs of ill-health, the detection of neutrophilia and "0" agglutinins and isolation of Salmonella organisms from faeces mainly served as evidence of recent infection. PMID- 2263745 TI - Streptococci from the bovine udder in dairy herds in Khartoum Province, Sudan. AB - Five hundred and seventy-nine milk samples were collected from dairy cows on seven farms in Khartoum North area and one farm in Omdurman and examined by bacteriological cultures for the presence of streptococci. One hundred and ninety three (33.33%) isolates were recovered and identified on the basis of bacteriological characteristics and biochemical reactions as: S. pyogenes, S. agalactiae, S. dysgalactiae, S. faecalis, S. faecium, S. bovis, S. equi, S. lactis and S. uberis. Fifty-seven isolates representing the preliminary identification were tested by the latex-agglutination test to determine the serological groups. It was found that 39 strains belonged to group B, 3 strains to group C. Four strains gave a weak reaction with group D sera and were identified by biochemical tests as S. uberis. Two isolates could not be identified by the available sera. The isolation of S. uberis, S. bovis, S. equi, S. lactis, S. faecalis, S. faecium and S. pyogenes from cows in the Sudan was reported for the first time. PMID- 2263746 TI - [Relation between tsetse fly density and bovine trypanosomiasis: the case of N'Dama cattle ranching (Louboulou, Congo)]. AB - The authors report the results of an entomo-parasitological survey in the State Ranch of Louboulou, Bouenza region, Congo. Over a period of more than five months, the average tsetse density was 0.2 Glossina palpalis palpalis captured per day and trap. Although some specimens of Glossina fusca congolensis were also captured, the density of the latter species was quite insignificant. No trypanosomiasis was detected among the N'Dama cattle of the ranch, as a result of 114 blood samples collected for parasitological (fresh blood sample, Woo method, thick blood film) and serological examinations (Testryp CATT on whole blood and serum). The absence of detectable trypanosomiasis is discussed and interpreted as a result of a low tsetse threat below a critical threshold which remains to be determined. PMID- 2263747 TI - Prevalence of domestic animal trypanosomiasis in the Fontem sleeping sickness focus, Cameroon. AB - Three hundred-fourteen domestic animals: 114 goats, 93 sheep, 67 dogs and 30 pigs in the Fontem sleeping sickness focus (Cameroon) were screened for infection with trypanosomes using parasitological and serological tests. Nannomonas was the only sub-genus detected in the animals with a prevalence of 28.3%. The card agglutination test (Testryp CATT) for trypanosomiasis showed a positivity rate of 38.2%, indicating that it allowed a better estimation of animal trypanosomiasis. The absence of trypanosomes of the sub-genus Trypanozoon seems to indicate that human African trypanosomiasis is not a zoonosis in this sleeping sickness focus. PMID- 2263748 TI - [Dominant characteristics of helminth parasitism in cattle in Ituri (Haut-Zaire). I. The helminth fauna]. AB - The identification of cattle helminths in Ituri was carried out by post mortem examinations in slaughterhouses and tracer calves. The thirty diagnosed species were typical of wet tropical areas of Africa. The presence of Dictyocaulus viviparus, Ostertagia ostertagi and Haemonchus similis and the absence of Echinococcus granulosus constituted the original features of this inventory. PMID- 2263749 TI - [Follow-up of a population of patients who underwent partial thyroidectomy for benign thyroid pathology]. AB - Natural history of partial thyroidectomy for thyroid disease has been studied in a population of 1196 consecutive cases surgically treated from 1977 to 1982. Follow-up analysis on this population (from six to eleven years) was carried out for appearance of recurrence. Generally, the recurrence incidence was small (only 9.9% of total population) but high frequency was observed for Graves' disease (46%) and lymphocytic chronic thyroiditis (21%). The substitutive/suppressive therapy administration did not influence recurrence of disease. Our results suggest that suppressive therapy does not modify the natural course of non cancerous thyroid pathology residual to partial thyroidectomy. PMID- 2263750 TI - [Significance of serum levels of beta-2-microglobulin in dialysis patients]. AB - beta 2M has been shown to be a major constituent of the amyloid deposits developing in uremic patients undergoing long-term hemodialysis. In this study, serum levels of beta 2M were determined in 67 hemodialysis patients and a mean +/ SD concentration of 57.8 +/- 18.5 mg/L was obtained. There was no difference in the concentration of the substance between the patients with evidence of dialysis related amyloidosis and those without it. Moreover, no correlation between beta 2M levels and duration of hemodialysis was found. Interestingly, the patients with residual diuresis had a significantly lower mean beta 2M concentration than the anuric patients (35.0 +/- 13.1 vs 62.8 +/- 15.8 mg/L, p less than 0.001). Not surprisingly, a significant decrease in the predialysis serum concentration of the substance was obtained after changing treatment from cuprophan hemodialysis to hemodialysis with high-permeable membranes (delta beta 2M = -16.1 +/- 14.4 mg/L at month 6, p less than 0.01). These results suggest the possible long-term use of these membranes to reduce risk of dialysis-related amyloidosis. PMID- 2263751 TI - [Pleural effusion in a case of non-Hodgkin's lymphoma: diagnostic use of molecular analysis]. AB - We describe a case of advanced non-Hodgkin lymphoma which lacked palpable superficial lymph nodes and in which conventional method did not allow a conclusive diagnosis. Recognition of lymphoproliferative disease was made by analysis at the DNA level of the configuration of the immunoglobulin and T-cell receptor gene regions. PMID- 2263752 TI - [2 cases of severe hypokalemia with acute rhabdomyolysis]. AB - We report two cases of acute rhabdomyolysis due to severe hypokalemia. The first case appears to be caused by a chronic dietary potassium deficiency, responsible also for the elevation of blood pressure and the impairment of myocardial contractility. The administration of hydrochlorothiazide, albeit associated with captopril, could have decompensated the potassium balance, thus precipitating the acute rhabdomyolysis. More commonly the second case is due to acute potassium losses induced by a trivial enteritis in a hypertensive patient who was taking thiazide diuretics for a long period of time. We emphasize that chronic dietary potassium deficiency may represent a predisposing variable to acute rhabdomyolysis, which is generally precipitated by the superimposition of other potassium lowering factors. PMID- 2263753 TI - [Prognosis in Hodgkin's disease: verification of a new predictive equation]. AB - A retrospective analysis of a series of 114 patients with Hodgkin's disease was carried out. The patient were male, aged greater than or equal to 45 years, histotype mixed cellularity or lymphocytic depletion, advanced stage (III o IV), ESR greater than 45 mm/1h., serum albumin less than or equal to 3.5 gr/dl appeared to be unfavorable parameters at diagnosis. The application of a predictive linear equation recently proposed by Gobbi et al. revealed a agreement between survival and predicted mean survival. PMID- 2263754 TI - [Usefulness of captopril test in diagnosis of renal artery stenosis and congenital small kidney in arterial hypertension]. AB - We studied 45 hypertensive subjects to evaluate the usefulness of captopril test for identifying renal artery stenosis and small congenital kidney with the hypoplasia of the renal artery. In 18 hypertensives with hippuran renogram indicating renovascular disease, and in 27 essential hypertensives, the plasma renin activity (PRA) responses to an oral test dose (50 mg) of captopril were studied. A 60-minute post captopril PRA increase of 150% (or 400% if baseline PRA less than 3 ng/ml/h) was considered as positive. Digital venous angiography was performed in all cases. In the group of 18 subjects small congenital kidney in 7, and renal artery stenosis in 11 subjects were detected by angiography. Captopril test resulted negative in all patients with small congenital kidney (mean PRA% increase 58). The test identified 7 of the 11 renal artery stenoses (mean PRA% increase 477), sensitivity and specificity were 64% and 100% respectively. In the essential hypertensives-group, mean PRA% increase was 122; there were three false positives, and both sensitivity and specificity were 88%. This study demonstrates that the PRA response to oral captopril test is a useful screening test for distinguishing small congenital kidney from renal artery stenosis and for identifying the latter in hypertensive patients. PMID- 2263755 TI - [Serum PABA test in diabetes mellitus]. AB - The serum values of para-amino-benzoic acid in subjects affected by type II diabetes mellitus, were measured hourly for 6 hours, after oral ingestion of B-T PABA. These values were compared with those of a control group. The results demonstrate that at 1, 2, 4 and 5 hours, the mean values of the two groups were significantly different: p less than 0.01, p less than 0.002, p less than 0.0001 and p less than 0.005 respectively. Comparing the area under the curve the data did not differ significantly, indicating that at the end of the sixth hours the quantity of PABA absorbed is very similar in the two groups. These results indicate that patients with diabetes seem to have an altered exocrine pancreatic function, which may be due to a reduction in the zymogen stocked in the acinar cells or a lower secretory response to physiological stimulus. This impairment does not affect the digestion and the nutritional state of the patients. PMID- 2263756 TI - [Allergic and pseudoallergic reactions to drugs]. PMID- 2263757 TI - Hyperventilation. AB - Physicians' and specialists' continued failure to recognise, diagnose and treat adequately the majority of hyperventilators is a disgrace. Hyperventilation Syndrome (H.V.S.), incorrectly labelled myalgic encephalomyelitis (M.E.), is the latest example of the profession's incompetence. Reasons for failure to teach doctors about H.V. are discussed followed by its incidence, and the tendency for patients to gravitate to Specialist Departments where general history and a complete physical examination have become more perfunctory as sophisticated tests have multiplied. Signs which should alert a clinician's suspicion are listed, which if present should lead to a series of suggested facilitating questions. Controversial aspects of tests to confirm diagnosis are discussed, and also recent work on the relationship of panic attacks to hyperventilation and vice versa. The need for understanding and how to elicit the typical psychopathogenesis is stressed. Lastly, a form of management is described which requires combined competent physiotherapy and competent psychological management. The latter involves uncovering the underlying psychopathology and then helping the patient resolve early loss or alienation which when reawakened by further losses or anticipated loss or surrogates, precipitate symptomatic H.V. PMID- 2263758 TI - Carcinogenesis bioassays of nickel oxides and nickel-copper oxides by intramuscular administration to Fischer-344 rats. AB - Five nickel oxides and nickel-copper oxides, with chemical compositions, physicochemical properties, and biological characteristics that were previously reported, were tested for carcinogenicity by administration to groups of male Fischer-344 rats as a single im injection (20 mg Ni/rat). Two additional groups of rats received injections of the glycerol vehicle (Negative Controls) or nickel subsulfide (alpha Ni3S2, 20 mg Ni/rat, Positive Controls). Within the observation period of 2 yr post-injection, the following numbers of sarcomas developed at the injection site: Negative Controls, 0/15; Positive Controls, 15/15; Compound A (INCO black NiO, prepared at less than 650 degrees C), 6/15; Compound B (grey NiO, calcined at 735 degrees C), 0/15; Compound F (green NiO, calcined at 1,045 degrees C), 0/15; Compound H (oxidized Ni-Cu matte, Ni/Cu = 2.5:1, calcined at 850 degrees C), 13/15; Compound I (oxidized Ni-Cu matte, Ni/Cu = 5:1, calcined at 850 degrees C), 15/15. The Ni- and Ni/Cu-oxides that induced sarcomas (Compounds A, H, and I) had measurable dissolution rates in body fluids and were strongly positive in an erythrocytosis stimulation assay, demonstrating Ni bioavailability. Compound A contained detectable Ni[III] and Compounds H and I contained Cu, plus traces of Fe, Co and S, which may all promote oxygen free radical reactions. In contrast, the compounds that did not induce sarcomas (Compounds B and F) were essentially insoluble in body fluids, did not stimulate erythrocytosis, and were practically devoid of Ni[III], Cu, Fe, Co, or S. Thus, the bioavailability of nickel and the presence of constituents that promote oxygen free-radical reactions evidently influence the carcinogenicity of nickel oxides and related compounds. PMID- 2263759 TI - A rapid, sensitive assay for gamma-aminobutyric acid in brain using electron capture gas chromatography. AB - A rapid, sensitive procedure has been developed for the assay of gamma aminobutyric acid (GABA) in brain tissue. The method involves sequential reaction with isobutyl chloroformate and pentafluorophenol under aqueous conditions and subsequent separation and quantitation of the derivative on a gas chromatograph equipped with a capillary column and an electron-capture detector. The method produces a derivative with good stability and provides for simultaneous analysis of GABA and five other aliphaticamino acids in very small volumes of supernatant from brain homogenates. PMID- 2263760 TI - Beneficial effect of cod liver oil in murine endotoxemia. AB - Cod liver oil (CLO), a marine fish oil, contains approximately 20% omega-3 fatty acids (OFA). When CLO is administered to humans, inhibition of platelet aggregation, decreased platelet arachidonic acid levels, and reduced levels of endotoxin-induced thromboplastin synthesis by monocytes are observed. Since endotoxin causes both increased platelet aggregation and monocyte generation of thromboplastin with resultant microvascular compromise, the purpose of this study was to determine whether CLO is protective in murine endotoxemia. Swiss Webster mice were given CLO (1.0mg, 10.0mg, or 100mg), or 100mg triolein (an unsaturated fat containing no OFA) or saline (control) intraperitoneally (IP) three hours prior to IP administration of 0.3mg E.coli endotoxin. Survivals at 48 hours post endotoxin administration were as follows: (A) 1.0mg CLO (4/20, 20%); (B) 10mg CLO (5/20, 25%); (C) 100.0mg CLO (11/20, 55%); (D) 100mg triolein (1/20, 5%); (E) 0.13cc saline (1/20, 5%). The significance of groups A,B,C,D verses the control group E is as follows: A vs E, p = 0.15; B vs E, p = 0.08; C vs E, p = 0.0006; D vs E, p = 0.76. This study demonstrates the beneficial effect of 100mg parenteral CLO in murine endotoxemia. This effect is probably mediated through antiplatelet and/or antimonocyte activating mechanisms. PMID- 2263761 TI - Effect of 5-hydroxytryptamine on gastric motility and efferent gastric vagus nerve activity in rats. AB - Intravenous administration of 5-hydroxytryptamine (5-HT) produced a depressor effect on pyloric pressure and an increase in the duration of this depressor effect on gastric pressure dose-dependently in anesthetized rats. Pretreatment with a selective 5-HT3-receptor antagonist, ICS 205-930 (10 micrograms/kg), inhibited these effects. Intravenous administration of 5-HT produced a dose dependent increase in efferent gastric vagus nerve activity (GVNA). A selective 5 HT3-receptor agonist, 2-methyl-5-HT, also produced a dose-dependent increase in GVNA. Pretreatment with a selective 5-HT3-receptor antagonist, ICS 205-930 (10 micrograms/kg), caused a shift to the right in both the 5-HT and 2-methyl-5-HT dose-response curves. These findings suggest that exogenous 5-HT activates efferent vagus gastric nerve activity and may trigger or mediate the gastric motility via 5-HT3-receptors. PMID- 2263762 TI - The effect of selenium ions on the catabolism of prostaglandin E2 in rabbit kidney cortex. AB - The effect of selenium ions on the catabolism of prostaglandin E2 by 15-hydroxy prostaglandin dehydrogenase and prostaglandin delta 13 reductase in rabbit kidney cortex was examined. Selenium ions had no effect on the 15-hydroxy prostaglandin dehydrogenase activity. On the other hand, selenium ions inhibited the prostaglandin delta 13 reductase activity at concentrations ranging from 0.05 to 0.5 mM. The effect was concentration-dependent. The inhibition by selenium ions was non-competitive with regard to NADH and 15-keto PGE2, respectively. These results suggest that selenium ions have the potential to increase 15-keto PG levels in the kidney by inhibiting the prostaglandin delta 13 reductase activity and that such action of selenium ions may participate in renal damage of selenium poisoning. PMID- 2263763 TI - Glutathione status, glutathione monoisopropyl ester, and cadmium metabolism in mice. AB - Glutathione monoisopropyl ester (GSHMI) was synthesized for an investigation of its interactions with cadmium (Cd) in mice. When administered ip prior to the injection of lethal doses of Cd given by the ip or sc route, it did not reduce Cd induced mortality. When given to Cd-bearing mice it did not promote mobilization of Cd from metallothionein-bound stores in liver, kidneys, spleen, testes, pancreas, or brain. When given at a dose of 6.0 mmol/kg 2 hr prior to administration of Cd, GSHMI enhanced Cd accumulation in kidneys, liver, spleen, and testes, and reduced the accumulation of the metal in brain. When 4.0 mmol/kg of the ester were given at various intervals prior to Cd administration, the major actions observed were substantial increases in Cd concentrations ultimately attained in kidneys and liver at most time intervals examined. Reductions of Cd accumulation were found only in liver and pancreas, and only when GSHMI treatment preceded Cd administration by 30 min. Reduction of endogenous GSH levels by administration of L-buthionine-(S,R)-sulfoximine (BSO) led to moderate increases in Cd accumulation in kidneys and pancreas; Cd deposition was reduced in spleen, testes, heart, lungs, and brain. BSO pretreatment led to only slight or no change in liver Cd accumulation. Sephadex G-75 gel filtration chromatography revealed that GSHMI pretreatment led to only a moderate and transient increase in hepatic Cd-metallothionein content when measured 2 hr after Cd administration; when assessed 1 hr and 3 hr post-Cd, elution profiles of extracts from livers of GSHMI pretreated mice were indistinguishable from control profiles. We conclude that GSHMI is not an effective agent for the control of Cd toxicity. PMID- 2263764 TI - [Merits and demerits of long acting formulation of cardiovascular drugs]. PMID- 2263765 TI - [Clinical significance of long-acting cardiotonics in therapy of cardiovascular diseases]. PMID- 2263766 TI - [Clinical significance of long-acting diuretics in the treatment of cardiovascular diseases]. PMID- 2263767 TI - [Clinical significance of long-acting antiarrhythmic agents and the combinations in the treatment of cardiovascular diseases]. PMID- 2263768 TI - [Comparison of cardiac output between in DDD and in VVI by pulsed Doppler echocardiographic method (correction with Swan-Ganz catheter method)]. AB - Difference of cardiac output and stroke volume between that in DDD and that in VVI was studied by pulsed Doppler echocardiography at different pacing rates. Moreover, to evaluate the usefulness of the method by pulsed Doppler echocardiography, cardiac output by the Swan-Ganz catheter method was measured and compared. Fourteen patients age 37-83 years (mean 65 years) with sick sinus syndrome and implanted multiprogrammable dual chamber pacemakers were studied. Cardiac output was measured as the product of the echocardiographically determined cross sectional area of the aortic anulus and the Doppler-determined mean velocity of left ventricular outflow over systole. Cardiac output was greater in DDD with atrial kick than in VVI at each pacing rate, and increased with elevation of the rate, but it was smaller at 120 PPM than at 110 PPM in DDD. Stroke volume was greater in DDD than in VVI at each pacing rate, and maximum volume was at 60 PPM in both modes. The data by pulsed Doppler echocardiography and by Swan-Ganz catheter method have high correlation. Besides being related with pulse rate, these results may be related with such things as myocardial contractility, preload and afterload. For example, the tension of autonomic nervous system, the changing of venous return volume, the disease of arteriosclerosis and old myocardial infarction, temperature, blood viscosity and so on. We will continue the study considering these factors. PMID- 2263769 TI - [Heart rate changes in sleep apnea syndrome]. AB - Sleep apnea syndrome (SAS) is often associated with arrhythmias. The study was performed to clarify the characteristics and mechanisms of the heart rate (HR) changes during and after sleep induced apneas. Thirty-one patients with SAS without definitive heart disease, aged 17-78 years (mean 54.2 years), were examined by electroencephalograms, electrocardiograms, electrooculograms, nasal and oral breathing, thoracic and abdominal respiratory movements and arterial oxygen saturation (SaO2). [Results and Discussion] At the onset of sleep apnea, some showed progressive reductions in HR, followed by abrupt tachycardia on the resumption of breathing. Thirty-one patients with SAS were classified into three Groups (A, B, C). Group A demonstrated that HR changes occurred associated with apnea both in stage REM and in stage non-REM. Group B demonstrated that HR changes occurred associated with apnea only in stage REM. Group C demonstrated that HR changes did not occur associated with apnea. In Group A, apnea frequency and apnea index were higher than those of Group C. In Group A, the lowest SaO2 was lower than that of Group C, total time under 90% of arterial oxygen saturation (SaO2) was longer than that of Group C. There was a good negative correlation between oxygen saturation and HR changes. Further, HR changes were augmented by arousal response. This might be related to the arousal response as well as to the cardiostimulatory effects of hypoxia associated with increased ventilation. The arousability in response to apneas might be important in HR changes. In SAS, the degree of HR changes was related to apnea frequency, apnea index, apnea length and sleep stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263771 TI - [Estimation of myocardial oxygen extraction dynamics in effort angina by continuous measurement of coronary venous saturation]. AB - To estimate myocardial oxygen extraction dynamics in the situation of increased myocardial oxygen requirement, we made a continuous measurement of coronary venous oxygen saturation (CSO2-Sat) using the fiberoptic catheter system and a measurement of myocardial lactate extraction ratio (MLER) in 14 patients. Ten patients showed ischemic ST depression and/or anginal episodes during the pacing loading, while 4 patients did not. Although transient decreases in CSO2-Sat were observed in the non-ischemic 4 patients immediately after the initiation of pacing or with the increase in pacing rate. CSO2-Sat and MLER remained almost unchanged from the start of pacing to the time of maximal pacing. However, in the 10 patients who developed ischemia, CSO2-Sat fell from 39.5 +/- 1.8% before pacing to 32.9 +/- 2.8% at the time of maximal pacing (p less than 0.05), with an average decrease of 6.6 +/- 2.8%. Data of MLER obviously indicated the appearance of myocardial ischemia (32.1 +/- 4.7% to 9.2 +/- 10.3%, p less than 0.05). These findings suggest that myocardial oxygen extraction will increase transiently or continuously to meet the myocardial oxygen demand when increase in coronary blood flow is limited. Continuous measurement of coronary venous saturation may be useful for the early detection of myocardial ischemia. PMID- 2263770 TI - [Fluid shear stress effects on intracellular calcium concentrations in cultured vascular endothelial cells]. AB - Vascular endothelial cells are known to modulate their functions in response not only to humoral stimuli but also to such physical stimuli as fluid shear stress generated by blood flow. However, the mechanisms by which the hemodynamic force acts on endothelial cells are not yet well understood. We have studied how endothelial cells recognize the shear stress and mediate it to intracellular organelles. Cultured monolayers of bovine aortic endothelial cells loaded with the highly fluorescent Ca+(+)-sensitive dye Fura 2 were exposed to different levels of fluid shear stress in a specially designed flow chamber and simultaneous changes in intracellular-free Ca+(+) concentration were measured using photometric fluorescence microscopy. Application of shear stress to cells by fluid perfusion led to an immediate several-fold increase in Ca+(+) concentration within 1 min, followed by a rapid decline, and finally a plateau somewhat higher than control levels during the entire period of the stress application. The early part of the response, but no plateau, was observed even in Ca+(+)-free medium added with 2 mM EDTA, and in the presence of calcium antagonists (e.g. 2 x 10(-5) M nicardipine). Thus, endothelial cells may have a flow-sensing property which recognize the shear stress on the membrane as a stimulus and mediates the signal to increase intracellular free Ca(+)+ which is a major component of the internal signalling system of the cell. PMID- 2263772 TI - [Primary coronary artery dissection: its incidence and genesis studied by clinical and coronary angiographic findings]. AB - The incidence and genesis of primary coronary artery dissection which occurred spontaneously in the coronary artery system were elucidated in this study. We examined clinical and coronary angiographic features of the patients who presented this dissection. Primary coronary artery dissection was observed in 23 (0.43%) of 5,400 consecutive patients with ischemic heart disease undergoing coronary angiography. The basic diseases were myocardial infarction in 17 cases and angina pectoris in 6. Sixteen patients (70%) had smoking habits, which might be related to this disease. The dissection of the right coronary artery in 12 cases, of the left anterior descending artery in 10, and of the left circumflex artery in only one was found. All lesions occurred in the proximal positions of the coronary branches. Seven (30%) of all cases had fixed coronary stenosis in other coronary branches. The other cases had "one-vessel" disease. Seventeen patients were treated medically, 5 had PTCA therapy and one had CABG operation. All the patients, except one who died of cancer are surviving in a 3.8-year follow-up. Patients can be divided etiologically into three groups. The first was comprised of those in the post- or peri-partum period. The second was those associated with coronary vasospasm, and the third was those with atherosclerotic coronary artery disease. The third group was the most frequent. PMID- 2263773 TI - [Role of systemic and pulmonary hemodynamics in genesis pleural effusion in congestive heart failure]. AB - We tried to make an estimate of how pleural effusion occur in congestive heart failure, using right atrial pressure (RA) and pulmonary arterial wedge pressure (PAW) as variables. We calculated the following equation by quoting the data in the past. RA greater than -0.02 x PAW + 13.3. We speculated that when this relationship is satisfied, pleural effusion will appear. We also studied the patients with severe congestive heart failure, dividing them into 2 groups, ie the pleural effusion group (EF) and pulmonary edema group (ED). Compared with ED, EF has a significantly higher RA (RA = 6.1 +/- 1.33 mmHg in EF and 13.3 +/- 2.21 mmHg in ED, mean +/- SE, p less than 0.02) and a significantly lower cardiac index (3.17 +/- 0.26 l/min/m2 vs 2.23 +/- 0.16 l/min/m2, mean +/- SE, p less than 0.01). Therefore, we thought that it was adequate to treat RA and PAW as independent variables. These equations appear to be useful in predicting the development of pleural effusion that's based in the plots of our patients on RA PAW plane and their relationship to our equations. PMID- 2263774 TI - [Contrast medium-induced expansion of circulating blood volume: Comparison between nonionic and ionic contrast media]. AB - We assessed whether the osmotic expansion of circulating blood volume (CBV) induced by nonionic contrast medium (NCM) is less than that induced by ionic contrast medium (ICM). Iohexol (Io) (NCM: 795 mO sm/kg H2O), 1.28 g iodine/kg, was injected intravenously into 5 mongrel dogs and blood samples were drawn at certain times. One week later, meglumine iothalamate (MI) (ICM: 1470 mOsm/kgH2O), 1.28 g iodine/kg, was injected into the same dogs. Another 5 dogs received MI first and Io one week later. Colloid oncotic pressure (COP) of the blood samples was measured by a needle osmometer, and changes in CBV were calculated from the COP values. The injection of Io or MI resulted in an immediate decrease in COP, and an increase in CBV at 1 min. MI induced significantly more severe and longlasting changes in COP and CBV than Io. Neither MI nor Io modified COP when they were added to the control blood samples. Thus, although NCM considerably expanded CBV, the magnitude of expansion induced by NCM was less than that induced by ICM. This may explain one of the reasons why NCM causes fewer adverse reactions than ICM. PMID- 2263775 TI - [A 38-year-old survivor with complete transposition of the great arteries]. AB - A 38-year-old woman with complete transposition of the great arteries (CTGA) was reported. She was admitted to Ehime University Hospital because of dyspnea on effort. She was diagnosed as CTGA with large ventricular septal defect (VSD) and pulmonary stenosis (PS) by magnetic resonance imaging. Survivors above 30 years of age are very rare in CTGA. The reason why this patient is still alive at the age of 38 seems to be due to PS that decreases pulmonary vascular resistance and VSD that mixes blood gas appropriately in the ventricle. PMID- 2263776 TI - [A case report of right ventricular infarction clearly detected by transesophageal echocardiography]. AB - We reported a case of a 70 year-old woman who suffered from right ventricular infarction with cardiogenic shock, detected clearly by transesophageal echocardiography. On admission, her pulse rate was 31 bpm and her blood pressure was unobtainable. Conscious level was III-1-2 and she was cold and clammy. The ECG showed complete AV block with junctional escape rhythm at a rate of 31 bpm which required temporary pacing and ST elevation in leads II, III, a VF, V4R, V3R, V1. An echocardiogram showed akinesis of RV free wall and paradoxical septal motion. Transesophageal echocardiography was performed safely on the 5th hospital day and detected RV wall motion abnormality clearly. A Swan-Ganz catheter was inserted. Mean PCW was 12 mmHg. PA pressure was 19/11 mmHg. Mean RA pressure was 13 mmHg. Cardiac index was 1.33 l/min/m2. SvO2 was 54%. Volume loading, administration of dopamine, dobutamine and nitroprusside were started. Cardiac index increased to 1.88 l/min/m2, and SvO2 increased to 59%. On the 4th hospital day, mean RA pressure increased to 29 mmHg and PA pressure increased to 47/31 mmHg acutely. Endotracheal intubation was done and PEEP 6 cmH2O was used and mean RA pressure and PA pressure decreased. On the 6th hospital day, cardiac index increased 4.08 l/min/m2. Cardiac catheterization done two months after acute myocardial infarction showed 75% stenosis of the proximal right coronary artery. PMID- 2263777 TI - [Familial complete atrioventricular block of adult onset]. AB - A family of complete atrioventricular block (FCAVB) of adult onset was reported. A 36-year-old-female had 1 degree AH block, atrial and ventricular premature beats and mild sinus node dysfunction. Her father had complete AV block and died of it. A 57-year-old uncle and a 52 years-old uncle had bradycardia from 44, 5 years of age and 51 years of age, respectively, and their ECG showed complete AV block with narrow QRS waves. They were implanted with permanent pacemakers. Her grandmother died a sudden death of Adams-Stokes attack. Acquired heart diseases were not seen in any of the family Thus, this family was thought a FCAVB of adult onset. PMID- 2263778 TI - [A case of myxedema with diffuse myocardial fibrosis proven by endomyocardial biopsy]. AB - We report a middle-aged woman with myxedema heart who presented both clinical features resembling dilated cardiomyopathy and the diffuse myocardial fibrosis proven by endomyocardial biopsy. Thirty years previously, when she was 36 years old, partial thyroidectomy had been performed after a diagnosis of hyperthyroidism was made. Four years later, she experienced dry skin and peripheral edema, and hypothyroidism was diagnosed. Several months after, replacement therapy for hypothyroidism improved her symptoms. However, the therapy was discontinued because of her ignorance of the disease. Twenty six years later (64 years old), she felt exertional dyspnea, and was admitted to Fukuoka University Hospital for evaluation of her cardiac state. Thyroid function test revealed primary hypothyroidism with low T3, low T4 and high TSH levels. Cardiothoracic ratio on chest X-ray film was 69%. Electrocardiogram showed low voltage in the limb leads and intraventricular conduction disturbance. Echocardiogram demonstrated marked dilatation and severely reduced wall motion of the left ventricle and pericardial effusion. Left ventriculogram showed diffuse hypokinesis with 27% of the ejection fraction. No significant stenosis was observed on coronary arteriogram. Seventeen-month replacement therapy did not improve these cardiac findings significantly. Transvenous right ventricular endomyocardial biopsy demonstrated diffuse myocardial fibrosis without inflammatory infiltrate, which was interpreted as a sequel of interstitial lesions of the myxedema heart such as edema or mucoid infiltration. This pathological finding suggests that long-standing untreated hypothyroidism can cause irreversible myocardial damage. PMID- 2263779 TI - [Hypertrophic obstructive cardiomyopathy in the right ventricle presenting in the elderly woman: a case report]. AB - A 69-year-old woman was admitted to the hospital for evaluation of a cardiac murmur, which had been indicated at her childhood. On physical examination, a systolic ejection murmur was heard on the lower left sternal border. Chest roentgenogram revealed a cardiomegaly. Echocardiography and MRI showed a thickening of the interventricular septum and the right ventricular (RV) free wall, which obstructed the RV body. At cardiac catheterization, a systolic pressure gradient of 100 mmHg was shown between the RV outflow tract and the apex. There was no pressure gradient in the left ventricle (LV). RV angiocardiograms disclosed a severe obstruction of the RV body, while LV angiocardiograms showed a slight enlargement of the LV with a diffuse hypokinesis of its wall. Myocardial biopsy of both ventricles revealed a bizarre hypertrophy of myocytes and disorganization. The histological findings were more conspicuous in the RV. Based on these findings, this case was diagnosed as hypertrophic obstructive cardiomyopathy (HOCM) in the RV. HOCM in the RV presenting in the elderly, is extremely rare. Our case is also characterized by a concomitant LV involvement, which demonstrated the slightly enlarged LV and the diffuse hypokinesis of its wall. PMID- 2263780 TI - Sloping alveolar plateaus of CO2, O2, and intravenously infused C2H2 and CHClF2 in the dog. AB - To investigate the role of the various mechanisms assumed to contribute to the slope of the alveolar plateau, two test gases exhibiting identical solubility but two-fold differing diffusivity, acetylene (C2H2) and chlorodifluoromethane (Freon 22, CHClF2), dissolved in saline were intravenously infused in 10 anesthetized, paralyzed, artificially ventilated dogs (mean body mass, 18 kg). The partial pressures of C2H2, CHClF2, CO2 and O2 during a constant-flow single-breath washout maneuver were recorded by mass spectrometry and analyzed in terms of slope of the alveolar plateau (phase III) and series (Fowler) dead space. The slope of the alveolar plateau (S) was determined as the relative alveolar slope normalized to mixed-expired partial pressure and referred to expired volume (VE), S(V) = delta PE/(PE - PI)/delta VE or expiration time (tE), S(t) = delta PE/(PE - PI)/delta tE (subscripts I, E, and E refer to inspired, instantaneous expired and mixed-expired gas, respectively). The effects of expiratory flow rate (VE), and time of breath-hold (BH) were studied with reference to control conditions (VI = 0.5 L.sec-1, VE = 0.1 L.sec-1, VI = 50% and VE = 75% of volume at FRC, BH = 0 sec). In control conditions, the following significantly different S(V) values (units: L-1), grouped in ascending order, were obtained (means +/- SD): CO2, 0.83 +/- 0.26; C2H2, 0.93 +/- 0.18; CHClF2, 1.00 +/- 0.20; O2, 1.07 +/- 0.29. The mean C2H2/CHClF2 ratio for S(V), 0.94 (SD +/- 0.03), was statistically different from unity. In line with model calculations, the experimental findings suggest that three mechanisms contribute to the sloping alveolar plateaus: 1, continuing gas exchange during expiration; 2, ventilation-perfusion inequality combined with sequential emptying; 3, intrapulmonary diffusion limitation. PMID- 2263781 TI - Alcohol and the response of upper airway resistance to a changing respiratory drive in normal man. AB - We studied the effects of alcohol ingestion on the response of upper airway resistance (UAR) to changing respiratory motor output in 9 normal subjects. Nasal and pharyngeal pressures were measured with two low bias flow catheters placed at the tip of the epiglottis and in the posterior nasopharynx. Respiratory flow was measured with a Fleisch no. 3 pneumotachograph connected to a tightly fitting mask. Breath-by-breath inspiratory upper airway resistances were calculated at isoflow during 1) a CO2 rebreathing (increase in drive), 2) 2 min following five slow vital capacities of 100% O2 (decrease in drive) (Post-O2 period), and 3) 1 min before each procedure (baseline measurements). The respiratory motor output was estimated by the pressure developed 0.1 sec after the onset of inspiration (P0.1) during rebreathing and by the mean inspiratory flow (VT/TI) during the post-O2 period. Measurements were performed before and after the ingestion of 1.5 ml/kg of 40% alcohol. Blood alcohol level rose from 0 to 14.9 +/- 1.8 mmol.L-1 (Mean +/- SD) and total supralaryngeal resistance increased from 2.8 +/- 1.8 cm H2O.L-1.sec to 4.2 +/- 1.8 cm H2O.L-1.sec (P less than 0.001, Student's paired t test). During CO2 rebreathing UAR decreased exponentially as P0.1 increased both before and after alcohol intake. The slope of the plot Log (pharyngeal resistance) against P0.1 decreased from -17.0 x 10(-3) +/- 9.3 x 10(-3) before alcohol to -11.0 x 10(-3) +/- 6.6 x 10(-3) after alcohol intake (P = 0.03). The slope of the decrease in nasal resistance remained unchanged. A decrease in VT/TI occurred during the Post-O2 period and was accompanied by an exponential increase in UAR at each experiment. The slope of Log (pharyngeal resistance) over VT/TI was significantly higher after (-27.0 x 10(-3) +/- 7.1 x 10(-3)) than before alcohol (-12.0 x 10(-3) +/- 4.2 x 10(-3), P less than 0.001). The slope of the increase in nasal resistance with decreasing VT/TI rose from -8.4 x 10(-3) +/- 6.5 x 10(-3) to -13.0 x 10(-3) +/- 7.4 x 10(-3) after alcohol ingestion (P = 0.06). We conclude that alcohol ingestion depresses the pharyngeal responses to changing central drive in normal subjects. PMID- 2263783 TI - Alteration in breathing of the awake rat after laryngeal and diaphragmatic muscle paralysis. AB - The respiratory rate (f), tidal volume (VT) and ventilation (V) were measured in 3 groups of rats: 10 rats before and after cutting both recurrent laryngeal nerves (RLNX), 10 rats before and after bilateral phrenicotomy (PNX) and 5 sham transected (SHAMX) rats. All rats were exposed to air and gas mixtures, deficient in O2 and/or enriched with CO2. The barometric method was used to measure ventilatory parameters. The sham operation did not affect breathing pattern or ventilation. In RLNX rats, breathing the various gas mixtures exhibited no changes in V because f uniformly increased as VT declined. Therefore, loss of the neural control of the respiratory functions of the larynx in awake rats exposed to selected gas mixtures has no untoward effects on alveolar ventilation. Changes in ventilation of PNX rats, compared with SHAMX rats, depends on the gas composition breathed. With increasing severity of hypoxia and/or hypercapnia, PNX rats show a marked reduction in alveolar ventilation over that of the SHAMX rats. Thus, when the diaphragm is no longer able to participate in ventilatory responses, gas exchange is likely to become deficient. PMID- 2263782 TI - Ventilatory and cardiovascular responses to hypoxic and hyperoxic static handgrip exercise in man. AB - The purpose of this study was to evaluate the ventilatory and cardiovascular responses to static handgrip exercise at different levels of arterial chemoreceptor activation. The study was done on 10 healthy subjects. They performed handgrip of 50% of maximal voluntary contraction on a background of either hypoxia (PE'O2 approximately 47 mm Hg) or hyperoxia (PE'O2 approximately 216 mm Hg), i.e., enhanced or suppressed chemoreceptor activity. The subjects were able to sustain the handgrip for 50-60 sec, during which time no steady state responses were attainable. Minute ventilation (VI), cardiac output (Q), heart rate (HR), and a number of other variables were recorded. Handgrip exercise resulted in a rapid initial VI rise followed by a subsequent slow increase. Hyperoxia diminished the VI response over the exercise range. The ventilatory response was associated with an HR acceleration, increased arterial pressure and peripheral vascular resistance. No appreciable changes in Q were noted, nor was there any particular relationship between ventilatory and circulatory changes. These results provide no support for the Q mediated ventilatory stimulus during static handgrip exercise in man. It is concluded that the ventilatory and cardiovascular responses are of independent nature. PMID- 2263784 TI - Acetylcholine and central chemosensitivity: in vitro study in the newborn rat. AB - In vitro experiments were performed in the superfused brainstem-spinal cord preparation of newborn rats in order to analyse the central respiratory effects of acetylcholine. The central motor output was assessed from recording electrical activity in nerves supplying respiratory muscles. Acetylcholine added to the bathing medium induced dose-dependent increases in respiratory frequency which were blocked by muscarinic (but not nicotinic) antagonists and enhanced by physostigmine. These effects originated from the medullary ventral surface where chemosensitive structures have been previously located. The respiratory central chemosensitivity of the isolated brainstem was analysed using a CO2 free, pH 7.9 medium instead of the normal medium (bubbled with 5% CO2, pH 7.3). Decreases at the H+ and CO2 stimuli led to decreased inspiratory activity, resulting mainly from a decrease in the amplitude of the motor output. These responses were enhanced by atropine and diminished by physostigmine. These results obtained in vitro on the newborn rat suggest that cholinergic synapses are not directly involved in the genesis of respiratory rhythmicity but confirm previous results obtained in vivo in adult animal revealing that acetylcholine is implicated in the central respiratory chemosensitivity. PMID- 2263785 TI - Japan Society of Sarcoidosis, 9th annual meeting. September 21-22, 1989, Nagoya. Proceedings. PMID- 2263786 TI - [Expansion of the medical faculty within the network of the Free University of Brussels]. PMID- 2263788 TI - [The medical faculty: present and future]. PMID- 2263787 TI - [50 years of A.M.U.B. (Association of Physicians graduated from the Free University of Brussels)]. PMID- 2263789 TI - [Role and range of the A.M.U.B. in the service of the faculty and its members (Association of Physicians graduated from the Free University of Brussels)]. PMID- 2263790 TI - [Clinical teaching in the hospitals of the city of Brussels]. PMID- 2263791 TI - [Genesis and initial steps of our medical faculty]. PMID- 2263792 TI - [Women and medicine]. PMID- 2263793 TI - [The A.M.U.B. and general medicine (Association of Physicians graduated from the Free University of Brussels)]. PMID- 2263794 TI - [History of the A.M.U.B.(Association of Physicians graduated from the Free University of Belgium)]. PMID- 2263795 TI - [The Revue medicale de Bruxelles]. PMID- 2263796 TI - The effects of nicotine on metabolic rate. PMID- 2263797 TI - Biomechanics of cycling and factors affecting performance. AB - Cycling performance in human powered vehicles is affected by the interaction of a number of variables, including environment, mechanical and human factors. Engineers have generally focused on the design and development of faster, more efficient human-powered vehicles based on minimising aerodynamic drag, neglecting the human component. On the other hand, kinesiologists have examined cycling performance from a human perspective, but have been constrained by the structure of a standard bicycle. Therefore, a gap exists between research in the various disciplines. To maximise/optimise cycling performance in human-powered vehicles requires a bridging of this gap through interdisciplinary research. Changes in different variables can affect the energy requirements of cycling. These variables include: (a) changes in body position, configuration, and orientation; (b) changes in seat to pedal distance; and (c) the interaction of workload, power output, and pedalling rate. Changes in these variables alter joint angles, muscle lengths, and muscle moment arm lengths, thus affecting the tension-length, force velocity-power relationships of multi-joint muscles and the effectiveness of force production. This is ultimately manifested as a change in the energetics of cycling. A large number of factors affect cycling performance in human-powered vehicles and a gap still exists between cycling research in various disciplines. To bridge this gap, if not completely close it, requires cooperation between disciplines and further interdisciplinary research. PMID- 2263799 TI - [What is your diagnosis? Sweet syndrome (synonym: acute febrile neutrophilic dermatosis)]. PMID- 2263800 TI - [Oncogenes]. PMID- 2263801 TI - [Long-term results following radioiodine treatment of patients with metastasizing follicular and papillary thyroid carcinoma]. AB - From 1963 to 1988, 94 patients with mediastinal and/or distant metastasis of follicular or papillary thyroid cancer have been treated in our department by subtotal or near total thyroidectomy, 131-iodine ablation of the thyroid recurrent thyroid hormone and 131-iodine applications. Patients with locally advanced tumours had also percutaneous irradiation. Some patients had also surgical excision and percutaneous irradiation of the metastasis. Rates of complete and permanent remissions were: 53% (all pap.), 7% (all foll.), 75% (lung and/or mediastinal metastasis), 100% (miliary or micronodular lung metastasis and small mediastinal nodes), 6% (bone metastasis). Tumor specific survival rates were: 95% and 90% 10 and 20 years in patients less than 40 years old at the beginning of the treatment, 65% (5 years), 40% (10 years), 25% (15 years) and 18% (20 years) in patients at least 40 years old. Serious complications due to radioiodine were observed in three patients (one acute leukemia, one macroscopic haematuria with irradiation cystitis and one cancer of the bladder). Furthermore five patients suffered from grade III/IV thrombocytopenia: these patients had also multiple bone metastasis and percutaneous irradiation of various bone regions. PMID- 2263802 TI - [Vision disorders in normal eye status]. AB - The origin of unusual visual phenomena is usually located in the brain or in the brainstem. They appear with normal ophthalmologic findings. Neurologic and ophthalmologic knowledge is needed for a localizing diagnosis and neuro-imaging is most often required. Selected cases of peripherally to centrally located lesions are presented. PMID- 2263804 TI - Recent advances in gynecologic malignancies. PMID- 2263798 TI - Psychological and behavioural effects of endogenous testosterone levels and anabolic-androgenic steroids among males. A review. AB - The psychological and behavioural effects of endogenous testosterone levels and anabolic-androgenic steroids in males have been investigated for over 50 years in both clinical and nonmedical uses, including the influence of anabolic-androgenic steroids on the nervous system and neuromuscular expression as a mechanism for behavioural and ergogenic effects. The relationship between moods, behaviour and endogenous plasma testosterone levels, as well as anabolic steroids and corticosteroid administration has been studied, including psychological dependence, withdrawal effects, and major methodological issues. While a relationship between endogenous testosterone levels and aggressive behaviour has been observed in various animal species, it is less consistent in humans. It can be concluded that, although the use of exogenous anabolic-androgenic steroids may have psychological and behavioural effects in some patients and athletes, the effects are variable, transient upon discontinuation of the drugs, and appear to be related to type (17 alpha-alkalated rather than 17 beta-esterified), but not dose, of anabolic-androgenic steroids administered. The roles of genetic factors, medical history, environmental and peer influences, and individual expectations are likewise unclear. In general, the evidence at present is limited and much additional research will be necessary for a complete understanding of this relationship. PMID- 2263803 TI - [A case from practice (200). Infection of the lower leg and upper arm caused by Mycobacterium marinum (aquarium granuloma)]. PMID- 2263805 TI - Gynecologic tumor markers. AB - The advent of monoclonal technology has increased the potential utility of antibody-dependent tumor marker assays in gynecologic oncology. The availability of unlimited quantities of several pure monoclonal antibodies directed against novel epitopes on tumor-associated antigens has permitted development of highly sensitive assays for serum markers. Traditional assays for human chorionic gonadotropin (hCG), NB/70K and TA-4 have been improved. CA 125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge is to identify new markers that will complement CA 125 in monitoring ovarian cancer and facilitate screening for occult early stage disease. Strategies involving multiple markers and modalities may be required. Some markers may emerge through a more fundamental knowledge of the biology of gynecologic neoplasms, including the expression of growth factors and their receptors. Finally, the application of monoclonal antibodies to immunohistochemistry and radionuclide imaging also may provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology. PMID- 2263806 TI - Pathology of gynecologic malignancies. AB - This review encompasses advances in the pathology of female genital tract tumors that have been deemed to have clinical significance. A number of newly described neoplasms are discussed as are the results of analyses of large series of cases of previously described tumors. Recent revision in terminology and the application of newer techniques for evaluating neoplasms, such as flow cytometry, are also briefly reviewed. PMID- 2263807 TI - Advances in radiotherapy in the gynecologic malignancies. AB - We review, for their wider applicability, four advances in the radiotherapeutic management of the gynecologic malignancies. Attempts at improving upon results obtained with radiotherapy by the addition of chemotherapy have usually followed one of two temporal strategies: Sequential chemotherapy-radiotherapy (so-called neo-adjuvant chemotherapy), or chemotherapy given concurrently with radiotherapy. The pros and cons of both models are discussed. Recent work suggests that there is a differential response between the acutely reacting normal tissues, as well as tumor, and the late-reacting normal tissues, which is dependent upon the radiation fraction size. The rationale and some important clinical applications are reviewed. Advances in brachytherapy include the high dose rate treatment and the use of rigid templates to guide the accurate placement of the interstitial implant. The controversies surrounding these approaches require further study before the precise place of these techniques is known. Finally, in vulvar cancer, the addition of radiotherapy to surgery is being studied to permit less radical operations in early disease, and greater local tumor control in advanced disease. PMID- 2263808 TI - Ovarian cancer. AB - Even though cisplatin-based combination chemotherapy results in increased clinical and surgical complete remission rates and improved median survival compared with single-agent alkylating agent chemotherapy, the 5 year survival rates for stages III and IV ovarian cancer have only improved to 25-30%. New methods being evaluated to improve response rates, median survival, and 5 year survival rates include the use of high-dose carboplatin, dose intensity using platinum compounds, intraperitoneal chemotherapy, concomitant intravenous and intraperitoneal chemotherapy, and the recent discovery of new active agents against epithelial ovarian cancer--Taxol, and Ifosfamide plus mesna. PMID- 2263809 TI - Recent advances in endometrial cancer. AB - There are well-defined prognostic factors that identify patients with clinical stage I (confined to the uterus) endometrial adenocarcinoma and patients at high risk vs. low risk for recurrent disease and allow for treatment tailored to those specific prognostic indicators. This had led the International Federation of Gynecologists and Obstetricians (FIGO) in 1988 to revise the FIGO staging from a clinical to a surgical/histopathological evaluation. The use of these prognostic factors should lead to improved initial surgery and adjuvant therapy for patients considered at high risk for recurrence. PMID- 2263810 TI - Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine exposure to diethylstilbestrol. AB - Intrauterine diethylstilbestrol (DES) exposure is associated with an increased risk for the development of clear cell adenocarcinoma (CCA) of the vagina and cervix. The age of the DES-exposed patients has varied from 7 to 34 years with the highest frequency from 14 to 22 years. The risk among the exposed is small and is on the order of 1 per 1,000. Factors that may increase the risk are maternal history of prior miscarriage, exposure to DES in early gestation, a fall season of birth, and prematurity. Pregnancy does not appear to influence adversely the tumor characteristics or prognosis of patients who have developed these malignancies. Criteria for appropriate local therapy of small clear cell adenocarcinomas of the vagina are presented. Recurrent CCA has been observed as long as 20 years after primary therapy emphasizing the importance of prolonged follow-up. PMID- 2263811 TI - Current management and treatment of squamous cell carcinoma of the vulva. AB - Treatment for squamous cell carcinoma of the vulva remains surgical, the standard procedure being radical vulvectomy and bilateral inguinal lymphadenectomy. There has been recent interest in refining histopathologic prognostic factors that would be highly predictive of regional lymph node metastases, recurrences, and survival. With such factors have come new innovative approaches to the management and treatment of minimally invasive carcinomas, regional nodal disease, and advanced lesions. These modifications from standard therapy could result in less morbidity, disfigurement, and hospitalization while not compromising survival. PMID- 2263812 TI - Invasive cervical cancer in the 1990s. AB - The death rate from invasive cervical cancer has decreased by 70% since the classic work by Papanicolaou and Traut in 1941 on the use of cytologic evaluation to detect cancer of the uterine cervix in the preinvasive in situ stage--a nearly 100% curable disease. Unfortunately, the survival stage for stage of invasive cervical cancer has remained static over the nearly 5 decades since their report. However, discoveries in the decade of the 1970s of the natural spread of cervical cancer, not only to the known pelvic lymph nodes, but the increasing incidence of paraaortic lymph node metastasis with advanced stages, the higher dose of radiation required to sterilize pelvic lymph node metastasis discovered at the time of radical hysterectomy or for locally advanced cervical cancer treated solely by radiation therapy, and the use of radiation potentiators, such as hydroxyurea, should lead to the significant reduction in the annual 7,000 deaths from this disease in the decade of the 1990s. PMID- 2263814 TI - [From posture to intiation of movement. International Neurological Meeting. Paris, 1-2 June 1989. Proceedings]. PMID- 2263813 TI - Immunotherapy of gynecologic malignancies. AB - Systemic Corynebacterium parvum and BCG have limited activity in gynecologic malignancies. Although intraperitoneal C. parvum is active, its toxicity is prohibitive. Intraperitoneal alpha-interferon is an active second line agent for minimal residual disease following combination chemotherapy. Intraperitoneal interferon trials are ongoing. Alpha-interferon is also active against lower genital tract condyloma acuminata. Sufficient numbers of patients have not been evaluated to determine the activity of interleukin-2(IL-2) in gynecologic malignancies. Radioisotope labeled monoclonal antibodies can image gynecologic malignancies and may have a future therapeutic role. The last decade has witnessed a substantial growth in immunotherapy and has demonstrated a role for biologic agents in cancer therapy. Continued improvement in biologic therapies should lead to major advances in gynecologic cancer diagnosis and therapy. PMID- 2263816 TI - Premotor area and preparation of movement. AB - Clinical observations indicate that lesions of the supplementary motor area interfere with the initiation of movement, whereas damage of premotor cortex (PMC) is associated with more complex motor dysfunctions. The clinical premotor syndrome is characterized by contralateral proximal weakness and limb kinetic apraxia in particular for the adjustment of proximal limb movements on both sides. Recordings of the movement kinematics show that the postural support and the assemblage of synergies between proximodistal muscle groups, but also between the two sides, is disturbed in patients with PMC lesions. Lateral premotor lesions of the dominant hemisphere produce a motor dysgraphia or motor dysphasia or both. Special tests disclose further deficits for example in sensory cued motor learning, as well as a severe disturbance of rhythm production without difficulties in rhythm discrimination. This indicates the involvement of PMC in the acquisition of motor skills and in the temporal organization of movement. There is evidence that PMC shows a similar pattern of somatotopic organization as in the primary motor cortex, but with a larger representation for proximal muscles. The present clinical evidence in conjunction with recent PET data and from magnetic stimulation is compatible with the view that PMC represents a bilaterally organized system involved in the acquisition and performance of skilled motor acts including speech and writing. PMID- 2263815 TI - [From posture to initiation of movement]. AB - Purposeful motor acts are subjected to two contradictory constraints. One is to move one or several body segments toward a goal, the other is to stabilize other segments in order to maintain posture and equilibrium. One of the major tasks of the central nervous system is to coordinate posture and movement. Human posture is built up from the superposition of several "modules' from the ground to the head. Each module, tied to the next one by muscles, has its proper central and reflex regulation which permits to maintain its position in relation to the underlying one. In addition, a global regulation of posture is apparent (postural tone). Equilibrium is maintained under static conditions when the center of gravity projects onto the ground within the supporting surface (feet). Sensory error detecting signals (visual, labyrinthine, proprioceptive) are correcting, through a feedback loop, the reference regulated value according to a "postural' body schema based on "metric' and "dynamic' inputs. Corrections are continuous (and slow) or discontinuous and phasic through a repertoire of synergies allowing fast corrections. During movement performance, posture and equilibrium are stabilized by "anticipatory postural adjustments'. Some are aimed at maintaining the equilibrium notwithstanding the displacement of body segments due to the movement; others stabilize one or several segments such as the head, the trunk or the arm, which serve as reference value for the calculation of the movement trajectory and for the accurate performance of the movement. The anticipatory adjustments are learned during childhood or during training for specific tasks. The adaptative networks built up for a given movement are then controlled by the movement related command signals. The central organization of these anticipatory postural adjustments relies on central brain structures involved in movement execution and movement organization. Deficit is seen in spastic patients, to some extent in cerebellar patients. Basal ganglia and premotor areas, including the supplementary motor area, are of importance for coordination between posture and movement. This suggests that one of their function might be to stabilize posture during movement performance in order to ensure precise reaching of the goal. A specific pathology of the anticipatory postural adjustments should thus be considered. PMID- 2263817 TI - Associated postural adjustments with body movement in normal subjects and patients with parkinsonism and cerebellar disease. AB - Sequential postural adjustments associated with the task of rising on tip-toes were investigated in a reaction time paradigm in 30 normal subjects, 10 patients with Parkinson's disease and 2 patients with cerebellar lesions. The typical motor pattern observed in normal subjects consists of preparatory activity in tibialis anterior (TA, shifting the body forward) and quadriceps femoris (QUA, stabilizing the knee joint) followed by executional activity in triceps surae (TS) resulting in the movement itself. Shortening of TS without preparation would result in shifting the body backward and in flexion of the knee. The coordinated pattern of motor activities is obviously adapted to functional demands. Leaning forward or backward prior to the movement results in additional adaptive changes in the timing of preparatory versus executional EMG activity, and in the amount of preparatory muscle force. The basic pattern of preparatory (TA and QUA) and executional (TS) activity was preserved in most patients with Parkinson's disease. Reaction times were normal or only moderately delayed. Time intervals between postural preparation and execution were also normal. But trial to trial variation of reaction times was increased. In the two patients with cerebellar disorders, motor preparation in QUA was delayed beyond TS onset. EMG activity was tonic and cocontraction of antagonistic muscles occurred. The basic pattern of motor preparation and execution was again preserved. It must therefore be generated outside the basal ganglia and the cerebellum. The temporal coordination of muscular activity within each and between the two components and scaling of muscle force are under cerebellar control. PMID- 2263818 TI - A new physiological concept on cerebellum. AB - A general functional model of the cerebellum is proposed based on recent anatomical physiological findings. A cerebellar microcomplex composed of a cortical microzone and a small cell group in a cerebellar or vestibular nucleus acts as an adaptive controller based on the synaptic plasticity of the long-term depression type in Purkinje cells, which is effected by control error signals of climbing fibers. Microcomplexes will be inserted in reflex arcs, command systems of voluntary motor control, and probably even cortical systems performing certain mental activities, providing adaptive-learning capabilities to these systems. PMID- 2263819 TI - The basal ganglia and the initiation of movement. AB - The positive and negative signs of basal ganglia disease provide strong clinical evidence that the basal ganglia and allied nuclei participate in the neural mechanisms underlying volitional activity. This chapter reviews the range of neural subsystems in the basal ganglia that may contribute to these functions and their relationships with the dopamine-containing cell groups of the substantia nigra. PMID- 2263820 TI - [Anatomo-physiologic substratum of akinesia in primates]. AB - Severe akinesia can be observed in macaques following MPTP injections destroying dopaminergic nigrostriatal neurons. Akinesia also results from inhalation of toxic substances inducing bilateral lesions of the two pallidal nuclei and of the pars reticulata of the substantia nigra, and not of the pars compacta. Most of the recent studies of the anatomo-physiological substratum of akinesia used MPTP injections. Deoxyglucose studies have shown a clear increase in the neuronal activity of the medial nucleus of the pallidum and of its thalamic projection territory. Electrophysiological studies have shown a major modification of the spontaneous activity of medial pallidal neurons which is influenced in an excessive and non selective manner by sensorimotor inputs. Analysis of the relative three dimensional geometry of nervous arborizations have shown that the striato-pallido-nigral system is extremely convergent. Akinesia consecutive to nigrostriate lesions could be linked to an excessive and anarchic activation of this system. The contradiction which exists between akinesia with an abnormal activity of the medial pallidum and akinesia with bilateral pallidal lesions could only be apparent if akinesia was linked to the ineffective emission or to the interruption of messages to the thalamus. PMID- 2263821 TI - Clinical neurophysiology of akinesia. AB - Akinesia refers to failure of willed movement to occur, and bradykinesia refers to slowness of movement that is ongoing. One mechanism of bradykinesia is failure to energize muscles up to the level necessary to complete a movement in a standard amount of time. Akinesia may occur for two possible reasons. One is that the movement is so slow (and so small) that it cannot be seen. A second is that the time needed to initiate the movement becomes excessively long; this can be studied by evaluation of reaction time. One simple factor in prolongation of reaction time is present in patients with rest tremor, who appear to have to wait for a beat of tremor in the agonist muscle of the willed movement in order to initiate the movement. Reaction time studies in patients with Parkinson's disease demonstrate that simple reaction time is delayed, while choice reaction time is normal. Additionally, there does not appear to be any slowness of thinking or difficulty with storage of a motor program. Hence, the difficulty with reaction time in these patients appears to be the time that it takes to execute a motor program. Studies with magnetic stimulation of the motor cortex during the reaction time period seem to support this hypothesis. Slowness of activation of the motor cortex to trigger a movement may well be analogous in mechanism to the slowness of bradykinesia. PMID- 2263822 TI - [Akinesia and associated motor involvement in Parkinson's disease and basal ganglia lesions]. AB - The paralysis due to lesions of the cortico-spinal tract disturb movements in their different modes while dissociated paralysis result from cortical and particular biopercular lesions. Movements cannot be executed on command whereas they are accomplished in their total complexity when they accompanied certain emotional states or when they are part of an automatic activity. Such a dissociation suggest that the motor program which does not respond to voluntary command will eventually be applied thanks to emotional or affective stimuli. Basal ganglia lesions induce other symptoms. The first to be observed concern the movements and postures implied in automatic series after learning. Akinesias which results from these lesions can be partially controlled by a voluntary command, particularly when helped by sensori stimuli. Such symptoms are observed sometimes from its beginning in the Parkinson's disease. Emotion and sleep are also able to improve these akinesias: therefore they appear either on a deficitary form implying a sensitive reinforcement or on a hyperactive form, which is alleviated by hypotonia and sleep. The localized lesions of striatum or of pallidum provoke identical symptoms but at the interruption of akinesia, a distortion of movement appears, contrary to what is observed in Parkinson's disease. Mechanisms of anticipation and adjustment of postural reaction are disturbed concerning not only the body axis but also the different segments of the limbs. This disturbance provokes unsteadiness and sometimes falls. At the level of the limbs the anomaly of postural reactions slows down the movement and disturbs specially the repetitive gestures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263823 TI - [Motor neglect: issues and prospects]. AB - Although the motor and sensory components of the neglect syndrome appear as dependent on a unitary attentional process, the clinical observation of pure motor neglect raises the possibility of segregation between attentional and intentional neural mechanisms. Neuroanatomical evidence suggests a separate role for the anterior and posterior cingulum. The anterior cingulum mainly projects to the supplementary motor area, the superior premotor area and the prefrontal granular cortex whereas the posterior cingulum mainly controls the inferior parietal lobule. The role of the intralaminar thalamic nuclei, together with the frontostriatal loops is considered. Behavioral neurology should strengthen its analytical approach in order to dissociate, by appropriate testing, the separate operations which contribute to relate perception and action. Several new hypotheses are presented. PMID- 2263824 TI - Electrophysiological correlates of movement initiation. AB - By averaging the electroencephalogram (EEG) or the magnetoencephalogram (MEG) of waking man in a manner time-locked to the onset of self-initiated volitional acts, movement-related potentials (or magnetic fields) can be recorded. In the preparation period, a slowly increasing cortical negatively called the Bereitschaftspotential (BP) or readiness potential, can be recorded. The BP precedes all our self-initiated (i.e. endogenous or willed) movements and actions by 1 sec or more prior to the onset of muscular contraction. The BP has 2 principal components, an early one which is bihemispherically symmetric, even prior to unilateral movements, and a late one which is lateralized towards the contralateral hemisphere. We have provided evidence (which was confirmed by regional cerebral blood flow studies) that the principal cortical generator producing the early component is the so called supplementary motor area ("SMA"), whereas the late asymmetric (contralateral) component is generated by the primary (rolandic) motor area, MI. The early "SMA"-related BP component may have motivational, intentional or timing properties, while the late component is related to synaptic facilitation in the contralateral MI area in preparation for the final pyramidal tract volley. In motor learning, the frontal areas are activated in both DC-potential recordings and emission CT experiments. The complete role of the "SMA" is not yet clear. However, it obviously has to determine the right moment to start a movement including the timing of single movements in motor sequences. It is particularly strongly activated in bimanual tapping of difficult rhythms. PMID- 2263825 TI - Brain regions involved in voluntary movements as revealed by radioisotopic mapping of CBF or CMR-glucose changes. AB - Mapping of cortical and subcortical grey matter active during voluntary movements by means of measurements of local increases of CBF or CMR-Glucose is reviewed. Most of the studies concern observations in man during hand movements using the intracarotid Xenon-133 injection technique, an approach that only allows to image the cortex of the hemisphere on one side (the injected side) of the brain. The results show that simple static or repetitive movements mainly activate the contralateral primary hand area (MI and SI); complex preprogrammed or spontaneous purposeful movements the supplementary motor area SMA on both sides increase in CBF/CMR-glucose and even internally ("mentally") going through the trained movements, causes such changes; complex purposeful movements also activate the premotor cortex, a response that is bilateral with greatest response contralaterally. Studies in patients with movement disorders are scant, but with the ongoing improvements in technique activation studies in selected patients may become an important tool in clinical neurophysiology/neuropsychology. PMID- 2263826 TI - [Is there a correlation between motor neglect and unilateral sensory neglect]. AB - Similarities between motor neglect and unilateral sensorial neglect are so striking that their mechanisms are likely to be almost the same. As the attentional interpretation is no longer possible for motor neglect, and the intentional interpretation may be dismissed in man because of the loss of automatic movements, the psychological interpretation must be abandoned. A purely physiological hypothesis is put forward for motor neglect. When applied to unilateral neglect, it suggests that sensorial signals treated by the right hemisphere do not reach a significant functional level. In such case, the left hemisphere assumed to be dominant for awareness of body and space would receive from the right hemisphere a message interpreted as nul and would neglect information coming from the left. PMID- 2263827 TI - [Artificial insemination with donor sperm. A model for the study of human reproduction]. AB - From the experience of the CECOS French Federation concerning artificial insemination with the donor's semen (AID), a certain number of facts about the natural fecundation of couples can be deduced. The study of healthy donors constitutes and interesting biological observatory as regards the norms of the semen characteristics, the epidemiology of sexually transmissible diseases, the epidemiology of genetic abnormalities. The study of the AID results indicates that the best day for fecundation ranges between D - 3 and D + 1 (D0 being the last lowest point on the temperature curve), the rate of success varies according to the quality of the cervical mucus, the age of the woman, the length of treatment, but also to the quality of the semen (numeration, mobility, teratospermia). These results vary also in inverse ratio to the quality of the husband's semen, thus showing that the sterility problem is well a problem of the couple. PMID- 2263828 TI - [Transsexualism]. AB - Transsexuals correspond in terms of their chromosomes, hormones and anatomy to their phenotypic sexual characteristics, but feel, with respect to their sexual identity that they unmistakably belong to the opposite sex, and wish for this reason to be reassigned to their psychological sex by means of endocrinological and operative treatment. They have a complete and permanent transposition of their sexual identity. The cause of transsexualism is unknown. There are male-to female and female-to-male transsexuals. The diagnosis is made by a psychiatric evaluation. Hormonal treatment before operation and lifelong substitution after castration are described. The surgical technique in male-to-female consists in castration and construction of a neovagina by inversion of the penisskin, evtl. mammaplasty -in female-to-male: mammatransformation, vaginal colpohysterectomy and adnectomy and in a second step perineoplasty and construction of a phallic urethra up to the glans of the enlarged clitoris. PMID- 2263829 TI - [When cancer of the endometrium is not a good cancer]. AB - Two groups of endometrial carcinomas (EC) are described: group 1 with associated adenomatous hyperplasia (AH) and group 2 without. Group 1 tumors are better differentiated, less invasive and almost never metastasize. Histologically, they are mostly glandular and well differentiated. Stromal foam cells were often present supporting the association with hyperestrogenism. Progesterone receptors (PR) were present in all tested cases, and their levels were high. The patients were often obese, nulliparous and had histories of estrogen intake; group 2 are less well or poorly differentiated EC, showed papillary, clear cell and anaplastic patterns, often invaded the myometrium and metastasized. PR were present in less than half of the examined cases, at low levels. The patients in this group were rarely obese, often multiparous had no history of estrogen intake; they were older than those in group 1. None of the patients of group 1 died of the disease, while about one fourth of the patients of group 2 died of EC. It was concluded that EC with no associated AH, therefore not hormonally "dependent" are cancers of higher virulence. PMID- 2263830 TI - [Urinary incontinence and prolapse. Medical treatment and functional treatment]. AB - Urinary continence implies that the variations of the vesical pressure does not exceed the capacities of the cervico-urethral closure system. The aim of the various methods of treatment is to have a beneficial action on those two parameters: drug therapy will mainly reduce the intra-vesical pressure (parasympatholytics...) and also improve the urethral tone (alpha adrenergics...), or have a mixed effect on both systems (tricyclic antidepressants, oestrogens...). The side effects are often numerous due to the impact on the vegetative or neuromuscular system. The re-education is complemented by: local and general kinesitherapy, sensorial retrocontrol, associated or not to electrotherapy. Motivation and active participation of the patient are essential. The indications covers all the various pathologies (perineal insufficiency, defects in the body pattern, prolapse, sphincteral insufficiency, transmission problems, vesical instability, urethral instability) and concerns patients of all age groups. PMID- 2263831 TI - [Urinary disorders during pregnancy and post-partum]. AB - In a study of 265 patients questioned in immediate post-partum, the authors observed a urinary incontinence during pregnancy in 46.4% of the cases and a post partum incontinence in 21.5% of the cases. These figures are comparable to those found in literature. In this study, in agreement with the authors, the post partum incontinence does not increase significantly when forceps have been used. On the other hand, it is exceptional after caesarian section. The incontinence observed during pregnancy and/or post-partum most often regresses in 60 to 80% of the cases. However, one can ask the question on whether it is not reveal a light pelvic alteration which could cumulate at each delivery. The difficulty to retain winds is observed in 26.7% of the cases. It seems to be correlated in a significant way to the use of forceps. The local--regional anaesthesia does not modify significantly the occurrence of urinary or rectal disorders. PMID- 2263832 TI - [The value and results of perineal-sphincteral rehabilitation in uro-gynecology]. AB - Urinary incontinence, considered as a taboo for a long time, is an invalidating condition which gives rise to several problems. About one person out of 20 suffers from it, that is, more than 2 million persons in France, half of whom are less than 50 years old. By an anatomophysiological and etiopathogenic review, the authors define the different causes of urinary incontinence in women, as well as other pathologies such as dyspaneuria or changes in the pelvic statics. They define the role, the indications and the limits of perineo-sphincteral re education, underlining the notions or prevention, particularly in post partum, and that of the complementarity with the various therapeutic approaches. PMID- 2263833 TI - [Use of fibrin glue in gynecology-obstetrics]. AB - The aim of the various fibrinogen-based biological glues is to reproduce and magnify the physiological coagulation processes. They can be defined as long-life reinforced clots. These glues have the following properties: adhesive property, haemostatic property, cicatrizing property, antiseptic property. Two proprietary medicinal products are actually available on the French market: Tissucol, Biocol. These glues require a preparation time of about 20 minutes; they can be used either drop by drop or continuously by spraying, with the use of a special device. PMID- 2263834 TI - [The significance of the level of C-reactive protein in gynecologic infections]. AB - C-reactive protein, synthesized by the liver, belongs to the group of proteins in the acute stage of inflammation. It has a very short half life of 6 to 8 hours with rapid evolution kinetics. The CRP level has been measured 959 times by the immuno-turbidimetric method in 500 in-patients of the Gynaecology Department of Claude Bernard Hospital. It was measured every 48 hours. The CRP level increases in the immediate post-operative period, reaches its maximum on D3 and falls back to normal between D5 and D7. The CRP level seems to be the most reliable parameter for the diagnosis of pelvic infections (namely salpingitis). It represents the best criterium to assess the effectiveness of the treatments administered to the infected patients (adnexitis, post-operative complications). PMID- 2263835 TI - [Do any indications remain for vaginal delivery in breech presentation?]. AB - The choice of the mode of delivery in breech presentations is still controversed, particularly in the primipara and in premature delivery. From the study of 277 cases of single pregnancy with a live baby in podalic position the authors analyze the indications for the mode of delivery as well as the foetal results. After 37 complete weeks of amenorrhea, labour was induced in 126 patients out of 248. 96 had a vaginal delivery. The labour comprises a certain number of risks, but gives the same results as the caesarian section. The primiparity does not seem to be a risk factor. Before 37 complete weeks of amenorrhoea, 7 babies were born by vaginal delivery and 22 by caesarian section. In case of foetal distress, the caesarian section decided too late does not avoid an unfavourable evolution, particularly in the very premature baby. Therefore, the indications for caesarian sections must be extremely large and decided without delay particularly before 32 complete weeks of amenorrhea. PMID- 2263837 TI - [The use of Thierry's spatula at the University hospital center in Toulouse in 1988]. AB - In 1988, 431 applications of Thierry's spatulae have been carried out at the Toulouse UCH (14% of deliveries). The indications, the modes of application and the results have been studied. The number of perineal tearings was slightly higher than that of spontaneous deliveries but quite comparable to the number recorded in university hospital departments which use other extraction instruments (namely Tarnier's forceps). 2 cervical lesions, against 1 in the spontaneous deliveries, and an equivalent number of vaginal lesions have been observed. However, the frequency of anaemias due to the bleeding during episiotomy, is clearly higher; this is due to the lack of experience of the operating staff. Finally, the ways of teaching the extraction techniques at the UCH are mentioned. PMID- 2263836 TI - [The hazards of forceps: the viewpoint of the pediatrician and the obstetrician]. AB - Neonatal and maternal complications observed after 410 forceps deliveries were retrospectively compared to those occurring after spontaneous vaginal delivery. Mild scalp and facial lesions as well as facial palsy were significantly increased in the forceps group. No severe maternal complications were observed. A short literature review was done, and other instrumental extractions were discussed. PMID- 2263838 TI - [Anti-prostaglandin agents in obstetrics]. AB - First the authors recall the synthesis cycles of prostaglandins and the main physiological effects of the latter. Taking into account these effects, antiprostaglandins can be used in two obstetrical pathologies: the threat of premature labour, the delayed intra-uterine development with or without toxaemia. In the particular case of the threat of premature labour, the authors report a certain number of clinical observations concerning non-steroidal anti inflammatory drugs and namely indometacin, showing the efficacy of the treatment. They also evoke the complications of this therapy where the stenosis of the arterial canal and its repercussion on the renal function predominate. They conclude with some practical advice. In the particular case of delayed intra uterine development with or without toxaemia, the authors put forward some physiopathological arguments leading to the use of the combination Aspirin/Dipyridamole. They report the results of their personal experience. Out of 52 cases taking platelet aggregation inhibitors, 43 are linked with an obstetrical pathology and amongst them, 86 p. cent have a pathological past record (severe toxaemia, isolated DIUD, DIUD + toxaemia, IUFD). In the great majority of cases, treatment was administered before 20 WA. The pregnancy progressed normally in 76 p. cent of the cases and all the pathologies observed were minor. No serious complications have been reported. The average term of pregnancy is of 38 WA with an average growth weight of 2,920 g. The efficacy seems better if the past record is a DIUD rather than a toxaemia. The authors then compare their results with the literature data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263839 TI - [The efficacy of Veinobiase in venous disorders presented in women taking estroprogesterone agents (a statistical study of 2,295 patients)]. AB - The authors tryed by a statistical study to evaluate the efficacy of aphlebotinic therapy in venous diseases induced or aggravated by estroprogestative contraception. During this study, it emerged that the induced functional venous problems were quite virtually corrected by this treatment. PMID- 2263840 TI - The prevention of cancer. PMID- 2263841 TI - Recent developments in medical oncology. PMID- 2263842 TI - Rhode Island patients undergoing outpatient chemotherapy. PMID- 2263843 TI - Recent advances in radiation oncology. PMID- 2263844 TI - Primary extranodal non-Hodgkin's lymphoma of the extrahepatic biliary tract. AB - A case of extranodal non-Hodgkin's diffuse, mixed small and large cell lymphoma of the extrahepatic biliary tract with jaundice as the initial manifestation is reported in this paper. Obstructive jaundice is very rarely an early symptom in lymphoma. The pathogenesis of jaundice in this case was infiltration of the extrahepatic bile duct by lymphoma cells and fibrosis. PMID- 2263845 TI - Myelomatous pleural effusion: report of an unusual occurrence. AB - Pleural effusion complicating the course of multiple myeloma is common. Myelomatous pleural effusion, in contrast, is distinctly rare. Searching the Medline data base, a total of only 35 previously reported cases could be located. A recent case we cared for prompted us to review the literature in this area. The incidence of myelomatous effusion, possible mechanisms of its formation, and implications for therapy and prognosis are discussed. PMID- 2263846 TI - Cancer in Rhode Island: focus on blacks. PMID- 2263847 TI - Recent advances in internal medicine. PMID- 2263849 TI - Recent advances in gastroenterology. PMID- 2263848 TI - Advances in nephrology: a selected review of progress in care of the patient with renal failure. PMID- 2263850 TI - Recent advances in pulmonary medicine. PMID- 2263851 TI - Recent advances in hematology. PMID- 2263852 TI - Advances in endocrinology and metabolism 1989-1990. PMID- 2263853 TI - Psychoneuroimmunology. AB - Complex interactions among the nervous, endocrine, and immune systems have been documented and these are currently being studied at the cellular and molecular levels with ever more powerful tools. They have an important impact on diseases affecting the three systems, in particular on autoimmune and infectious diseases of the nervous system. In time neuroimmunological diseases and psychoneuroimmunological relationships may become as "respectable" as the more familiar neuroendocrine diseases and relationships. PMID- 2263854 TI - [Humidification and aspiration of the respiratory tract in patients with mechanical ventilation]. AB - Mechanical ventilation through endotracheal prosthesis, suppresses the nose functions and stops elimination of secretions. It is mandatory to heat artificially, humidify insufflated gas and to suction tracheobronchial secretions. Heating humidifiers are very efficient for the first purpose but heat and moisture exchangers, a little less efficient, seem to be a good alternative as they are easiest to use and offer a good bacterial protection. Tracheobronchial suctioning has to be carried out at least each four hours and at the best as soon as adventitious sound are heard in the chest. Suction catheters have to be atraumatic; vacuum has to be between -200 to -400 cm H2O; catheter have not to be pushed further than the carina; suction hypoxemia can be reduced by shortening suction maneuver, by using suction catheter with little diameter, by conducting the suction on mechanical ventilation. PMID- 2263855 TI - [Tissue oxygenation during recovery from anesthesia. Value and measurement]. AB - The measurement of tissue oxygen concentrations in the intensive care unit is important for the management of patients, especially those in shock. In daily practice, right heart catheterization with continuous monitoring of the oxygen saturation of mixed venous blood provided means of evaluating the principal parameters of oxygenation (transport, consumption and extraction), and of analyzing therapeutic interventions. The finding of an oxygen debt implies an appropriate therapeutic response designed to balance oxygen supplies with peripheral oxygen demand. PMID- 2263857 TI - [Hyponatremia of acute pulmonary infections]. AB - The mechanism of hyponatremia associated with pneumonia has been debated. In particular, the responsibility of inappropriate antidiuretic hormone secretion has been questioned. We have shown that inappropriate antidiuretic hormone secretion is a nearly constant finding during pneumonia and is roughly proportional to the extent of pneumonia. Nevertheless, it must be emphasized that extracellular fluid volume may be increased, diminished or normal during pneumonia, depending on the underlying condition (congestive heart failure, cirrhosis) or on the importance of extrarenal losses (sweats, fever). Careful clinical and laboratory assessment of extracellular fluid volume should enable adequate therapy. PMID- 2263856 TI - [Syndrome of multiple organ failure]. AB - The multiple organ failure syndrome (MOF) is a relatively new entity defined as the successive occurrence of respiratory (ARDS), hepatic, renal, myocardial, gastro-intestinal or neurological failure in patients with hyperkinetic haemodynamic and hypermetabolic states. The etiologies are: infection, septic and non-septic shock, burns and multiple injuries. The MOF syndrome is considered to be a generalised "inflammatory reaction" to tissue aggression involving a cascade of mediatory factors (TNF, interleukines...) of macrophagic, lymphocytic origin, causing multiple organ failure. The treatment depends on early correction of cellular hypoxia related to circulatory disturbances, nutritional support, anti infective therapy and, in the near future, "control of mediator activity" (immunotherapy). PMID- 2263859 TI - [Current modalities of mechanical ventilation for acute respiratory failure in chronic respiratory insufficiency]. AB - Acute respiratory failure in patients with chronic obstructive lung disease is a frequent and serious complication, with a mortality rate of 20 p. 100 and 57 p. 100 of the patients kept under mechanical ventilation for more than two weeks. The main problem with mechanical ventilation is an unavoidable intrinsic positive expiratory pressure and a hyperinflation that can be increased by the different modes of ventilation. All the classical modes of mechanical ventilation may be used, including control-mode ventilation, assist/control-mode ventilation, intermittent mandatory ventilation and ventilation with inspiratory assistance. Another major problem is weaning from mechanical ventilation as it may take a long time or even be impossible, so that the patients stay in intensive care units for ages or require long-term home ventilation. At the moment, there is no way of predicting the outcome of weaning in each individual subjects, and none of the various ventilation procedures has proved superior to the others. Nasal ventilation has recently been introduced in intensive care where it constitutes a major step forward being less invasive; it avoids intubation in 60 p. 100 of the patients but is more exacting for the physicians and nursing staff; finally, it makes it possible to treat acute respiratory failure at an earlier stage than previously. PMID- 2263858 TI - [Upper respiratory tract infections in patients with tracheal intubation]. AB - Nosocomial sinusitis (NS) is observed in 10 to 30 per cent of patients under mechanical ventilation (MV) and in up to 40 per cent in those with nasotracheal intubation. This complication occurs in the first two weeks of MV in 3 out of 4 cases. Apart from a pyrexia, the clinical signs are inconsistent. Radiography at the bedside using a cradle to immobilize the head, shows either opacification of the sinus or a fluid-air level. Cerebral CT scanning is justified when intracranial extension of the infection is suspected. NS is the source of many complications: parasinusitis, intracranial infection, septicemia, and, above all, nosocomial pneumonia. The treatment requires withdrawal of nasal tubes, cleaning the nostrils, nasal decongestants and drainage after transmeatal puncture. The latter procedure enables samples of pus to be taken for bacteriological investigation. The potential gravity of NS justifies a systematic work-up in all patients on MV and strict surveillance of the efficacy of the chosen treatment. PMID- 2263860 TI - [Single lung transplantation]. PMID- 2263861 TI - [Treatment-resistant arterial hypertension]. PMID- 2263862 TI - [Occlusion of the central vein of the retina and its branches. Etiology, diagnosis, development and prognosis; principles of treatment]. PMID- 2263863 TI - [Gastroesophageal reflux and hiatal hernia. Physiopathology, diagnosis, development and prognosis, medical treatment and principles of surgical treatment]. PMID- 2263864 TI - [Splenomegaly. Diagnostic trends and management]. PMID- 2263865 TI - [Obsessive neurosis and obsessive compulsive disorders. Diagnosis, principles of treatment]. PMID- 2263866 TI - [Typhoid fever. Epidemiology, etiology, physiopathology, diagnosis, clinical course and prognosis, treatment]. PMID- 2263867 TI - [Factors affecting normal levels of insulin, cortisol, STH, thyroxine and triiodothyronine]. AB - Published "normal" values of some hormones have an excessively wide range and unequal mean values because the material on which these values are based is from subjects suffering from different diseases which only apparently are not associated with the investigated hormone, or else the specimens are obtained under non-standard conditions (malnutrition, stress, alcohol etc.). This wide range of normal values may hide incipient pathological processes and is not suitable even as control group. The investigation is based on the assessment of insulin, growth hormone (GH), cortisol, thyroxine (T4) and triiodothyronine (T3) in a group of blood donors. The assembled results were compared with two other groups of blood donors and a group of obese subjects. The following findings were assembled: We recommend to lower the upper borderline of "normal" insulinaemia from the recommended value of 26 to 20 i.u./l, as the original range may comprise milder forms of hyperinsulinism which is recently assumed to participate in the genesis of type 2 diabetes, hypertension, coronary ischemia and polycystic ovaries. Elevated normal values of serum insulin may be obtained also from blood donors who usually have breakfast before the blood is collected. The wide range of cortisolaemia is due to the diurnal rhythm. The basal value is raised by a declining blood sugar level, alcohol, obesity and of course, varying forms of stress. The upper range of cortisolaemia at 8 a.m. should not be beyond the range of 140-690 nmol/l. GH secretion is governed by an individual 3.5-hour cycle as well as changes of the blood sugar level, e. g. during the OGTT: the declining blood sugar level raises the GH level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263868 TI - [Early changes in the structure of venous grafts, their prevention and significance]. AB - The authors investigated, using optic and electron microscopy, the course of regressive changes in smooth muscle cells of the media in venous grafts, in relation to various physical and chemical factors. They recorded the influence of a temperature of 4 degrees C and 22 degrees C, the influence of various types of crystalloid and colloid solutions and some pharmaceutical preparations. In previous work they found that, as a result of ischaemia, regressive changes take place in the smooth muscle cells of the media, while plasmatic structures of these cells and fibrillar structures of the venous wall remain intact. They provided evidence of the adverse effect of crystalloids, where the regressive changes can be detected already after 30 minutes. A protective effect on the nuclear structure is exerted by colloids, in particular a 6% solution of detoxicated haemoglobin. More favourable results were achieved at 22 degrees C. Some pharmacological preparations have a favourable effect on the preservation of the structure of cellular nuclei. The authors draw attention to the importance of these changes for clinical practice. PMID- 2263869 TI - [The LDH virus and changes in cellular immunity in schizophrenics and their relatives]. AB - In a long-term investigation the authors investigated in a group of schizophrenics and their grade 1 relatives the immunological response to schizophrenic cortex (from the frontal and temporal lobe) and to LDH viral antigen (lactate dehydrogenase virus). In the group of 261 subjects (84 patients, 60 parents, 37 siblings) a significant increase of a certain type of cytophil antibodies was detected, manifested by positive reactivity to gray matter of the schizophrenic and healthy brain, not only in patients but also in their parents and siblings who were healthy from the clinical and psychiatric aspect. At the same time a highly positive immune response to the LDH viral antigen was found not only in patients but also in their relatives. In some positive subjects, in particular as regards the viral antigen, the number of non-adhered cells in the LAI test (Leucocyte adherence inhibition) exceeded 100% which suggest leucocyte proliferation. Microscopic examination revealed repeatedly that during two-hour leucocyte incubation with antigen at 37 degrees C in these subjects enhanced mitotic leucocyte division occurs. This finding was recorded in 22% of all positive schizophrenics and in 13% of the parents; in healthy siblings (although they had a positive immune response to the viral antigen) direct cell division did no occur in any of the cases. Assessment of circulating immune complexes revealed positive values in a total of 93% of all investigated subjects. As compared with controls (80 mentally and physically healthy blood donors), the mean levels are more than double and the difference is highly significant (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263870 TI - [Biochemical monitoring of pregnancy with a hypotrophic fetus]. AB - The authors attempt to compare the asset of three biochemical parameters in monitoring pregnancies threatened with foetal hypotrophy. In 46 pregnant women hospitalized on account of suspected intrauterine retardation of foetal growth 121 oestrogen estimations in 24-hour urine were made, 83 examinations of serum oestriol and 101 examinations of trophoblast-specific beta-1-globulin (SP1). The authors evaluated the first collected specimen and well as repeated examinations. In women who were delivered of a hypotrophic foetus, in 72.2% there was a pathological course of urinary oestrogens and in 50% of serum oestriol and SP1. At least one of the evaluated indicators was pathological in 94% of the patients. From the results ensues that in biochemical investigations of pregnancies with a retarded intrauterine foetal growth it is useful to investigate several biochemical parameters in a parallel way. It is, however, essential to assess them dynamically as, a single examination does not provide sufficient information. PMID- 2263871 TI - [Serum beta-2-microglobulin in breast carcinoma]. AB - By including biochemical examinations in routine practice possible early detection of tumours is enhanced. In the submitted paper the authors assessed by radioimmunoassay beta-2-microglobulin in serum of patients with mammary tumours. In mammary cancer elevated values were recorded in 42%. PMID- 2263872 TI - Effect of metoclopramide on portal blood flow in patients with liver cirrhosis, measured by the pulsed Doppler system. AB - The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemodynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemodynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 +/- 1.1 to 10.8 +/- 1.2 cm/sec and from 769.0 +/- 87.7 to 707.9 +/- 84.2 ml/min, respectively (p less than 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p greater than 0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension. PMID- 2263873 TI - The occurrence and extent of Helicobacter pylori colonization and antral and body gastritis profiles in an Estonian population sample. AB - A series of 143 subjects representing an Estonian urban population was examined for the occurrence and extent (absent, mild, moderate, severe) of Helicobacter pylori colonization in antral and body biopsy specimens (Giemsa staining). These data were correlated with the presence and grade of chronic gastritis (normal, mild, moderate, or severe superficial chronic gastritis; mild, moderate, or severe atrophic gastritis) in the antrum and the body. Gastritis of any grade was found in the antrum and/or the body in 140 (98%) subjects. The overall extent of H. pylori colonization in the whole series did not differ between the antrum and the body. Of 93 subjects with superficial gastritis, H. pylori was found in the antrum and/or the body in 87 (94%) cases. Of 47 subjects with atrophic gastritis in the antrum and/or the body. H. pylori was not found in 12 (25%). In subjects with gastritis the absence of H. pylori either in the antrum or in the body was relatively common (in 30 of 143 subjects). The grade of superficial gastritis showed a highly significantly positive correlation with the extent of H. pylori colonization in the antrum but not in the body. Correspondingly, the grade of atrophic gastritis in the antrum correlated negatively to the grade of colonization. The total absence of H. pylori was particularly associated with the absence of gastritis in the antrum. Conversely, severe body H. pylori colonization was found in subjects who had atrophic antral gastritis, and severe antral colonization in subjects who had at least moderate superficial antral gastritis and who showed a coexistent normal or slight superficial gastritis in the body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263874 TI - Effect of transcutaneous nerve stimulation on esophageal motility in patients with achalasia and scleroderma. AB - It has been suggested that low-frequency transcutaneous electric nerve stimulation (TENS) alleviates the dysphagia produced by achalasia and scleroderma of the esophagus. The present study was conducted to elucidate whether TENS treatment improves dysphagia because of changes it induces on esophageal motility. We studied nine achalasia patients before forceful dilatation of the cardias, nine achalasia patients after dilatation, and nine patients with scleroderma. High-frequency TENS was applied to the hand for 30 min while esophageal motility was monitored by manometry. In none of the groups did TENS produce any change in the basal tone of the lower esophageal sphincter, lower esophageal sphincter relaxation, or esophageal body wave amplitude. Low-frequency TENS, used in another seven untreated achalasia patients, also did not improve esophageal motility. Our data indicate that high- or low-frequency TENS does not induce detectable changes in esophageal motility in patients with achalasia or scleroderma. PMID- 2263876 TI - Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis. AB - Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results were compared with preoperative endoscopic retrograde cholangiopancreatography (ERCP) morphology. The preoperatively elevated pressure decreased in all patients but one, to normal or slightly elevated values. The median pressure decrease was 50% (range, 0-90%; p = 0.01). The drainage anastomosis (a pancreaticogastrostomy) was made in the body of the pancreas, but the pressure decrease in this region was not significantly different from that in the head and tail. The pressure decrease was independent of findings during ERCP (stone, total duct obstruction, or major ductal stenosis). In conclusion, the results showed a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings. PMID- 2263875 TI - Protective effect of S-adenosyl-L-methionine in hepatic uroporphyria. Evaluation in an experimental model. AB - The potential use of S-adenosyl-L-methionine (SAMe) as therapy for human porphyria cutanea tarda was investigated in an experimental model of hepatic porphyria--that is, chronic treatment of female rats with 0.2% hexachlorobenzene (HCB) in the diet. Administration of SAMe (25 mg/kg subcutaneously twice daily) during the last 15 days of HCB administration halved porphyrin accumulation in the liver but did not alter HCB-induced massive inhibition of uroporphyrinogen decarboxylase. Equally unaffected were inhibition of glutathione peroxidase and stimulation of lipid peroxide formation induced by HCB. Hypothetically, the beneficial effect of SAMe on hepatic porphyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphate. PMID- 2263877 TI - Pancreatic tissue fluid pressure in chronic pancreatitis. Relation to pain, morphology, and function. AB - The relation between pancreatic tissue fluid pressure and pain, morphology, and function was studied in a cross-sectional investigation. Pressure measurements were performed by percutaneous fine-needle puncture. Thirty-nine patients with chronic pancreatitis were included, 25 with pain and 14 without pain. The pressure was higher in patients with pain than in patients without pain (p = 0.000001), and this was significantly related to a pain score from a visual analogue scale (p less than 0.001). Patients with pancreatic pseudocysts had both higher pressure and higher pain score than patients without (p = 0.004 and p = 0.0003, respectively). The pressure was significantly related (inversely) to pancreatic duct diameter only in the group of 19 patients with earlier pancreatic surgery (R = -0.57, p = 0.02). The pressure was not related to functional factors or the presence of pancreatic calcifications. In conclusion, pancreatic tissue fluid pressure is a valuable indicator of pain in chronic pancreatitis. PMID- 2263878 TI - Primary gastric non-Hodgkin's lymphoma in Finland, 1972-1977. Clinical presentation and results of treatment. AB - During the period 1972-1977, 66 patients were treated for primary gastric non Hodgkin's lymphoma in various hospitals in Finland. Most frequently, the disease occurred in middle-aged or old patients and had a male predominance. Clinical symptoms were non-specific. An abdominal mass was felt in 21% of the patients. Roentgenologic findings were mostly non-specific but suggested a malignant tumour. A definitive diagnosis was difficult to confirm by endoscopic examination. Forty-four patients had surgical resection, 30 patients curative resection, and 14 palliative resection, and 16 patients had only explorative laparotomy. Eighty-five per cent of the patients who had curative resection survived 5 years, compared with 15% of those who underwent palliative resection. Curative resection gave the best survival of 5 years. The stage of the disease was a very important prognostic factor: the 5-year survival was 85% for patients with stage-I disease but only 3% for those with stage-IV disease. PMID- 2263879 TI - Cholecystokinin is responsible for growth of the pancreas after pancreaticobiliary diversion in rats. AB - Pancreaticobiliary diversion (PBD) caused a more than twofold increase in pancreatic weight after 10 days, with no further increase after 15 or 20 days or 7 weeks. Although the weight gain after PBD to a minor extent (10%) reflected increased water content, the main cause was hypertrophy and hyperplasia with increased pancreatic protein and DNA content. The cholecystokinin (CCK) concentrations in plasma were increased 10-fold from the 5th postoperative day. The trophic effects on the pancreas were completely abolished by the CCK antagonist L-364,718. Further, the antagonist caused a significant reduction in pancreatic weight, protein, and DNA in otherwise untreated controls. We conclude that PBD in rats induces trophic effects on the pancreas by increasing circulating CCK concentrations and that CCK is important for normal pancreatic growth. PMID- 2263880 TI - Reproducibility of ambulatory gastric pH recordings in the corpus and antrum. Effect of food, time, and electrode position. AB - The reproducibility of simultaneous, long-term, ambulatory gastric pH recordings in the antrum and corpus was investigated in nine healthy subjects who underwent three separate, 27-h gastric double pH-metries. Intraindividual reproducibility for the entire 27-h recording period was good in the corpus (Kendall's concordance coefficient, W' = 0.6393, p less than 0.025) but not in the antrum (W' = 0.4806, NS). Analysis of predefined time periods showed that non-meal daytime pH was reproducible in the corpus (W' = 0.6531, p less than 0.025) but not in the antrum (W' = 0.3395, NS), whereas mealtime pH was reproducible in the antrum (W' = 0.7159, p less than 0.005) but not in the corpus (W' = 0.4954, NS); nocturnal pH was not reproducible in either the antrum or the corpus. These results reflect the functional separation of corpus and antrum and their differing responses to food. Thus, studies of gastric acidity over long periods should be conducted in the corpus, whereas studies of gastric acidity over shorter, meal-related periods should be conducted with a second electrode in the antrum. PMID- 2263881 TI - A technique for screening of achlorhydria and hypochlorhydria during upper gastrointestinal endoscopy. AB - Measuring of the intragastric pH during upper gastrointestinal endoscopy examination was performed perendoscopically with a monocrystalline antimony electrode, which was passed through the biopsy channel of the endoscope. The procedure was easily performed, resulting in only a few minutes' delay. If the pH found was 3.5 or above, the patients were later sent for a subcutaneous pentagastrin aspiration test. There was a close correlation between the lowest intragastric pH measured via the endoscope and the lowest pH measured in the gastric juice aspirated under basal conditions (r = 0.673, p less than 0.0001). An endoscopically assessed pH of 4.0 was the lowest level above which patients with achlorhydria or hypochlorhydria were found, according to the subsequent pentagastrin test. Fifty-five per cent of the patients with a perendoscopically assessed pH of 4.0 or above were achlorhydric. PMID- 2263882 TI - The aetiology of gastric stump carcinoma in the rat. AB - This study investigated the aetiology of gastric stump carcinoma in the rat. These carcinomas were induced by duodenogastric reflux without the need to administer carcinogens. Carcinoma was only detected when pancreatic exocrine secretions were present in the reflux. Malignant change was associated with dysplasia but not intestinal metaplasia or adenocystic proliferation of glands. The extent of resection increased tumour yield, but a truncal vagotomy did not. No difference was detected in intragastric pH, bacterial flora, or bile acid concentration between animals with and without carcinoma. PMID- 2263883 TI - Cumulative 10-year risk of symptomatic duodenal and gastric ulcer in patients with or without chronic gastritis. A clinical follow-up study of 454 outpatients. AB - The cumulative rate of symptomatic peptic ulcer (PU) was examined in a 10-year clinical follow-up study of 454 consecutive outpatients who had undergone diagnostic gastroscopy, from whom routine biopsy specimens were taken from the antral and corpus mucosa, and who were found to be ulcer-free before and at the time of this initial gastroscopy. During the follow-up period 34 (11%) of 321 patients who showed gastritis in the biopsy specimens at the initial gastroscopy had contracted symptomatic PU (18, 5, 7, and 4 cases of duodenal, pyloric, antral, and angular or corpus ulcer, respectively), which was verified by endoscopy. Only 1 (0.8%) of 133 patients with normal antral and corpus mucosa had contracted PU. It was calculated that the 10-year cumulative probability of PU was 10.6% (95% confidence interval (CI95), 7.2-14.0%) in the patients with gastritis, whereas this probability was only 0.8% (0-2.2%) in the patients who had normal antral and corpus mucosa in the initial specimens. The cumulative probability of PU was found to be highest, 27.3% (1.0-53.6%), in middle-aged men (41-60 years of age) who had chronic antral gastritis or chronic pangastritis (gastritis in both antrum and corpus). It is concluded that chronic gastritis precedes the appearance of PU and that the cumulative 10-year risk of PU is very low when both antral and corpus mucosa are normal but may be high if chronic gastritis is present. PMID- 2263884 TI - Five-year cimetidine maintenance trial for peptic ulcer disease. A clinical and endocrinologic approach. AB - A multicentre maintenance trial was conducted in 63 peptic ulcer patients to investigate the efficacy and safety of continuous cimetidine maintenance therapy for up to 5 years. In Amsterdam the male patients were investigated yearly for possible endocrinologic changes and to monitor gastric acid secretory capacity. Patients with healed ulcers entered maintenance treatment with a 400-mg bedtime dose of cimetidine. The yearly relapse rates decreased from 20% to 6% from year 1 to year 4. Adverse reactions observed in this study were not different from those previously reported with cimetidine. Endocrinologic studies in 10 male patients showed a small but consistent increase in basal gastrin in the 3rd and 4th year, stabilizing in the 5th year. Prolactin levels showed a gradual increase during the first 3 years but remained well within the normal range. In the 4th and 5th year they decreased again; however, the changes noted were rather modest. It is concluded from this study that weak nocturnal acid inhibition with cimetidine maintenance treatment not only continues to be effective and safe beyond 1 year but also reduces the risk of relapse over time. No relevant endocrinologic abnormalities are to be expected with this regimen of modest nocturnal acid suppression. PMID- 2263885 TI - Gene and haplotype frequencies of HLA antigens in 269 patients with Crohn's disease. AB - Evidence of strong genetic markers in Crohn's disease (CD) is still absent. Many investigations have focused on HLA antigens, with conflicting results. To obtain more detailed information on the relation of HLA to the disease, we used the HLA data from 269 CD patients to compute the maximum-likelihood estimates of HLA gene and haplotype frequencies. These results provide further evidence that HLA B44 and Cw5 do indeed play a role in the development of CD. Furthermore, it is conceivable from our results that HLA Cw7 may protect against being affected with this disease. PMID- 2263887 TI - The efficacy and safety of long-term maintenance treatment of duodenal ulcers with ranitidine. PMID- 2263886 TI - A prospective randomized comparison of two different pelvic pouch designs. AB - The clinical manovolumetric, and functional results of restorative proctocolectomy were studied in patients randomly allocated to construction of either a J-shaped pouch (n = 29) or a pouch fashioned by the folding technique used for the Kock continent ileostomy (K-pouch) (n = 26). A complete endoanal mucosectomy was performed, and the pouches were all constructed from 30-cm lengths of ileum. There were no deaths and no significant difference in postoperative morbidity. Anal pressures were equal in the two groups. The K-pouch expanded more favourably postoperatively, and its volume at 1 year was significantly greater than that of the J-pouch (355 +/- 71 ml (SD); range, 225 495, versus 264 +/- 81 ml; range, 75-440; p less than 0.001). The pouches had similar motility patterns and sensory pressure thresholds. Initially after closure of the loop ileostomy there was a tendency for better functional outcome in K-pouch patients. At 1 year the overall distribution of functional defects did not differ, and the defaecation frequency was about equal in the groups. PMID- 2263888 TI - Sexually transmitted infections. Current epidemiological perspective on world wide infections with aspects on transmission, molecular biology, epidemiological control and prevention. Berzelius Symposium XVII, Swedish Society of Medicine, 22 24 May 1989, Orsundsbro (Uppsala), Sweden. Proceedings. PMID- 2263889 TI - Persistence of hepatitis B virus and establishment of delta virus infection. AB - A typical feature of an infection with the hepatitis B virus (HBV) is the development of a persistent infection manifested by a chronic carriership of hepatitis B antigen (HBsAg). There is a marked geographical variation in the frequency of the chronic HBsAg carrier state. The replication of the HBV is unique for a DNA virus and has functional characteristics of a retrovirus, i.e. replication of viral DNA through an RNA intermediate. In addition to episomal viral DNA involved in virus replication other episomal forms and integrated viral DNA have been found in infected cells. The integrated HBV DNA in liver cells is an essential factor in the development of hepatocellular carcinoma. Many epidemiological studies have made it clear that age, sex and immunological status are important factors predisposing to the development of chronic infection. Hepatitis D virus (HDV) is a distinct infectious agent but it is defective as it requires the helper function of HBV for its replication. There are two possible modes of infection, either a coinfection, i.e. simultaneous infection with HBV and HDV, or a superinfection, i.e. a chronic HBsAG carrier who becomes infected with HDV. The majority (70-90%) of all superinfections take a chronic course. PMID- 2263890 TI - Persisting inapparent chlamydial infection in a trachoma endemic community in The Gambia. AB - In a Gambian village with endemic trachoma, C. trachomatis was isolated from some 50% of children with active trachoma but from only 1% of adults with scarring sequelae. One possibility is that individuals with progressive scarring disease have clinically inapparent, non-productive infection which cannot be detected by cell culture. In whole village survey, 12% of 808 people carried ocular chlamydial antigen detected by EIA. Around 70% of antigen positive children were clinically active. By contrast, for adults age greater than 25 years, only 10% of antigen positives were clinically active. Antigen positive adults were twice as likely to develop scarring disease and longitudinal studies suggest that they are intermittently infectious. Implications for the pathology and prevention of trachoma are discussed. PMID- 2263892 TI - Epidemiology of HIV infections. Design options with special reference to developing countries. AB - Health research and planning need valid data for decision making. In a developing country cost-effectiveness in research design is of special significance. In such situations, population-based data are needed. This paper reviews the literature on HIV/AIDS studies published during 1982-88 with respect to epidemiological methods and study designs and with special relevance to developing countries. A methodological taxonomy is presented based on this review illustrating the special need for analytic epidemiology. The paper also presents experiences and results from an ongoing collaborative project on HIV infections between Tanzanian and Swedish researchers. The project, which was launched in 1987 in the Kagera region where the first AIDS cases were seen in 1983, applies both epidemiological and behavioural methods. PMID- 2263891 TI - Epidemiologic control of genital Chlamydia trachomatis infections. AB - Sexually transmitted diseases (STD), whether old or new, impose a heavy economic burden on the public health service. Behavioural changes that could reduce the incidence of STD in the general population take time to make their effects felt. Common and treatable diseases such as genital chlamydial infections can and should be tackled by the old familiar strategy for combatting STD, viz. case finding, diagnosis, contact tracing and treatment, parallel with counselling in sexual behaviour. The incidence of infection is largely dependent on the number of asymptomatic individuals with a chlamydial infection in the population. Case finding programs devised chiefly for young, sexually active people will thus directly influence the natural life of Chlamydia trachomatis in our society. One such program, involving the sampling of women below the age of 30 when they come to the family planning clinic (FPC) for contraceptive advice, when applying for legal abortion, or when receiving prenatal care has been running in Halmstad, with increasing effect, since 1982. Contact tracing is an important part of the program. The prevalence of infected women has been halved since 1984 in the age interval 15-29 years. 10% of infected females, 15-24 years old, evidence repeated infection during 1 year. This program, carried out at a FPC, has proved cost effective, achieving a 44% reduction in calculated expenditure. Chlamydial infections in Sweden are changing in character from being an untreated hyperendemic disease up to the late 1970s, to become a treated hyperendemic disease, until at last a declining prevalence can now be discerned. PMID- 2263893 TI - Human immunodeficiency virus, genital ulcers and the male foreskin: synergism in HIV-1 transmission. AB - Epidemiologic studies in Nairobi and elsewhere in Africa, have shown that men infected with HIV-1 more commonly have a history of genital ulcer disease compared to uninfected men. In one study, HIV infected men were three times as likely to have a recent history of genital ulcers. In a prospective study of seronegative men, those presenting with chancroid had a five-fold risk of seroconversion during follow-up compared to men presenting with urethritis. Uncircumcised men had an increased risk of seroconversion which was independent of their risk of genital ulcer disease. Over 95% of attributable risk in men with STD was either genital ulceration or the presence of a foreskin. Genital ulcers are a major risk factor for HIV infection among prostitutes. The increased risk is about 10-fold among prostitutes with ulcers compared to a cohort who did not. We hypothesize from these studies that genital ulcers are the major portals of entry for HIV infection and also increased shedding of virus infected cells into the vaginal secretions. HIV seropositive prostitutes are more susceptible to chancroid with a two-fold increase in the prevalence of genital ulcers as compared to HIV negative women. The use of condoms by their clients prevents both genital ulcer disease and HIV acquisition among prostitutes. Chancroid is more difficult to treat in HIV infected men with one-third of patients failing single dose treatment regimens as compared to less than five percent of men without HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263894 TI - Age-dependent sexual behaviour amongst male homosexuals and the transmission dynamics of HIV-1. AB - The paper describes the development of an age-structured model of the transmission dynamics of HIV-1 in a male homosexual population with age-dependent rates of sexual partner acquisition, and explores the properties of the model by means of numerical methods. Age-dependency in rates of sexual partner change acts to increase the initial growth rate of the epidemic and raises the equilibrium level of endemic infection in the population when compared with the prediction of a model without age structure but with identical initial overall population mean rate of partner acquisition. In addition, age-dependency in sexual activity acts to induce demographic changes in the population where the younger more sexually active males represent an increasing proportion of the population as the epidemic develops over time. One consequence of this is an increase in the overall population mean rate of sexual partner change as a direct result of the mortality induced by AIDS in the older less sexually active classes who acquired infection at a younger age. The results are discussed in relation to the interpretation of current patterns of HIV-1 spread and the acquisition of quantitative information on sexual behaviour. PMID- 2263895 TI - Potentials for change. AB - Taking as a point of departure the perspective of a behavioural scientist the need to move from a clinical to a sociological perspective is stressed. The difference between microsociologically and macrosociologically induced changes is emphasized. The former depending on interpersonal relations and to some extent open to our conscious efforts to achieve change. The latter depending on major social transformations which we usually cannot manipulate according to our wishes. We are here faced with a dilemma since our wishes for changes in sexual behaviour usually are of a magnitude that would require macrosociologically induced changes (which we cannot control) whereas our ability to interfere in the process is limited to microsociologically induced changes (which will not produce the results we hoped for). In view of this it is argued that it is necessary to act within the bounds of our respective cultures and to establish not only general objectives but also culture specific targets. These may, however, often appear to be in conflict with more general values in a given society. This reflects a perennial dilemma in occidental culture where sexual behaviour on the one hand is to be love based (and thus at least partly irrational) and on the other hand to be responsible (i.e. extremely rational). PMID- 2263896 TI - Vaccines against STDs: specific considerations? AB - Sexually transmitted infectious diseases continue to be an important threat and has through the appearance of HIV-AIDS increased in significance. In the present article a brief survey is made in relation to whether STDs present unusual problems to the immune system when vaccines are considered. The conclusion is that certain parameters involved in infections are exaggerated in sexually transmitted diseases. No special or unique obstacles are, however, present which may block the vaccines to function efficient against STDs. A summary is then made taking as a special case the problems involved when attempting to produce a vaccine against the major present threat amongst STDs namely HIV. PMID- 2263897 TI - The epidemiology of trachoma predicts more blindness in the future. AB - Trachoma is considered the world's leading preventable cause of blindness, with hundreds of millions of people affected and approximately 6 to 9 million blinded as a result of the disease. It was once endemic in much of the world. It disappeared from most of Europe and North America, coincident with the improvements in hygienic conditions that accompanied the expanding industrial revolution in the latter part of the 19th century. Common wisdom states that trachoma is disappearing from much of the world today as a result of improvement in the standard of living. Unfortunately, this is not a realistic perception. In some hyperendemic areas neither the standard of living nor hygienic conditions are improving. Deaths due to acute infections have been reduced and the population is both growing and aging. In some parts of the world, because of demographics, it is likely that there are more people being exposed to trachoma as children and more will survive to old age when trachomatous blindness develops. In these countries there will be larger numbers of blind individuals in the future than there are today. This will tax public health and economic systems in the involved communities. PMID- 2263898 TI - Epidemiological and clinical aspects on infections due to Chlamydia pneumoniae (strain TWAR). AB - Recently a new species of Chlamydia has been recognized and named Chlamydia pneumoniae, strain TWAR. This organism has now been causally associated with respiratory infections in humans. Serosurveys demonstrate the universal distribution of this pathogen all over the world. The antibody prevalences increase from a few per cent in pre-school children to 20-30% in teenagers. They then increase at a slower rate with prevalences of 40-60% in adults. Antibodies to the TWAR strains have so far been detected only in humans but not in birds or domestic or pet animals suggesting humans as the sole host for these organisms. The isolation and propagation of the TWAR strains and the development of monoclonal antibodies have made diagnosis of infection by these pathogens possible. PMID- 2263899 TI - Gonorrhoea and syphilis in Sweden--past and present. AB - Gonorrhoea and syphilis that belong to our oldest recognized sexually transmitted diseases (STD) are also the prototypes of curable STDs. After the discovery of the causative organisms, Neisseria gonorrhoeae in 1879 and Treponema pallidum in 1905, diagnostic tests were developed and by this, in conjunction with instituted regulations and legislation, means were created for public health authorities to collect statistical data. Sweden has fairly reliable statistics of both syphilis and gonorrhoea from 1912 and onwards, and these data show many interesting characteristics. Syphilis was prevalent in Sweden among both males and females during World War (WW) I and peaked in 1920 with an incidence rate of 150 and 75 per 100,000 population, respectively. The incidence figures fell rapidly after 1920 and reached a low of less than 30 cases per 100,000 in the mid 1920s, probably as a result of systemic treatment with Salvarsan in conjunction with vigorous contact tracing, two important measures to bring an infectious disease under epidemiological control. There was a slight increase of male syphilis in the late 1920s and early 1930s, and of both male and female cases during WW II which never reached the incidence figures of WW I. Penicillin was introduced in the mid 1940s for treatment and was proved superior to Salvarsan. The incidence figures have been very low ever since the early 1950s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263900 TI - Pelvic inflammatory disease and related disorders; novel observations. AB - All efforts and economic resources allocated to different means to restore possibilities for women with obligated and damaged fallopian tubes to conceive and of involuntary childless couples to adopt children stress the disability of persons with such sequelae of pelvic inflammatory disease (PID). In contrast, preventive measures have so far obtained much less resources. At present, the number of PID cases in Sweden that become hospitalized has markedly decreased during recent years. This decrease preceded that of the number of diagnosed cases of gonorrhoea but preceded the level off and recent slight decrease of chlamydial cases seen in Sweden. Whether the decrease of PID cases represent a true decrease or not is not known. There has obviously been a shift to a greater proportion of non-gonococcal (chlamydial cases) versus gonococcal PID cases in Sweden. The former type of cases may generally have a milder clinical course which might mean the PID cases nowadays more often are low symptomatic or even asymptomatic and will thereby often be treated in ambulatory practice or not all all. The use of oral contraceptives may protect against ascending infection by chlamydiae, but not against gonococci. This may have a marked influence on the epidemiology of PID in Sweden. There are evidence of chronic tubal chlamydial infection often passing undiagnosed and that the diagnosis is first established in conjunction with ectopic pregnancy or infertility investigation. Ectopic pregnancy as a sequelae of chlamydial salpingitis is on its increase in most countries, including Sweden. The incidence of ectopic pregnancy generally follows more than 5 years after a chlamydial infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263901 TI - The epidemiology of HIV and other sexually transmitted infections in the developing world. AB - As for several other infectious diseases, sexually transmitted diseases (STD) in many developing countries are characterized by a high incidence and prevalence, a high rate of complications and sequelae (particularly in women and neonates), a different clinical spectrum (more genital ulcer disease), and a severe problem of antimicrobial resistance (in N. gonorrhoeae and C. trachomatis). In Africa, HIV is mainly spread heterosexually, resulting in a major problem vertically acquired HIV infection in children. STDs, in particular those associated with genital ulceration, are enhancing the efficiency of sexual transmission of HIV, and their high prevalence may partly explain the occurrence of a major heterosexual epidemic of HIV in Africa, as opposed to Europe. Factors contributing to the spread of STDs are to a large extent demographic, sociobehavioural and medical such as a larger pool of adolescents and young adults, prostitution, urban migration, indiscriminate use of antibiotics and inadequate medical facilities and STD control programmes. Programmes for the prevention and control of STD and AIDS should be an immediate priority in many developing countries. PMID- 2263902 TI - Genital infections and reproductive health: infertility and morbidity of mother and child in developing countries. AB - Genital infections in impoverished countries take a heavy toll both in the etiology of childlessness and in pregnancy-related morbidity, both for the carrier (mother) and the passenger (fetus/newborn). Tubal damage is by far the most common single etiology in cases of childlessness. Among the three factors principally contributing to childlessness, infertility, pregnancy wastage and child loss, tubal infertility is the predominant one. Prevalence figures of N. gonorrhoeae among women in reproductive ages range between 5 and 15% in several countries. Similar figures prevail among pregnant/puerperal women. Preliminary figures indicate that prevalence of Chlamydia trachomatis is similar. Genitally acquired infections during pregnancy contribute to pregnancy wastage in the second and third trimesters of pregnancy. There is virtually no data to support that HBV, HSV and HPV significantly contribute to transmitted intra-uterine disease leading to pregnancy wastage. In the third category of childlessness, child loss, HSV and HIV play a well-known role. Maternal and neonatal morbidity is adversely affected by genital infections acquired during pregnancy. While hepatitis in some places is an important contributor to maternal mortality and morbidity, other viral diseases like HSV and HPV do not appear important in pregnancy-related maternal morbidity. Gonorrhea and chlamydia infection give few maternal problems during pregnancy but may be more important as a cause of puerperal endometritis-myometritis, which constitutes one of the leading causes of maternal death in many developing countries. The fetal/neonatal infant morbidity is affected by gonorrhea and chlamydia infection, while HSV is less frequent but extremely serious when it appears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263903 TI - [Post-resection states after surgery for gastroduodenal ulcer disease]. AB - A total of 115 patients with gastroduodenal ulcers submitted to surgery at the Department of Surgery in Hradec Kralove between 1975 and 1979 had been reported on retrospectively. Authors emphasized the long term postgastrectomy results providing minimally 10-year-lasted intervals since. After a detailed clinical examination of patients, postgastrectomy results may be evaluated as good ones and comparable to a number of literary experiences. Therefore, they estimate this surgical modality of treatment to be justified and appropriate in respect with contemporary indicatory criteria as well as other therapeutic modalities known to exert influence on gastroduodenal ulcers. PMID- 2263904 TI - [Partial ileal bypass in the treatment of hyperlipidemia]. AB - The hyperlipidemia may be influenced with both the conservative and surgical management. Starting from 1987, authors use Buchwald's (1963) partial ileal bypass method. They report on their experience with 16-membered total of patients. In majority of patients, the PIB was auxiliary operation mostly in relation with vascular reconstructive surgery. No lethality case or serious complication has been stated. All patients showed the substantial decrease in cholesterol and triglyceride levels, these being normalized in majority of patients. Authors are discussing PIB indications. The suggestion is made that this is the most effective of known measures in attempt to achieve a continual decrease in lipids without the serious discomfort for a patient. PMID- 2263905 TI - [Carcinoma of the gastric stump]. AB - The problems related to the postgastrectomy cancers occurrence are studied in the present work. A total of 65 subjects with postgastrectomy stump's cancer has been managed at Clinic of surgery in Hradec Kralove starting from 1955 to 1984. An interval averaged as 26.4 years followed from the gastrectomy up to the cancer' occurrence in postgastrectomy stump. Such an interval was stated to be longer in gastrectomized younger patients. Postgastrectomies of II. type resulted in stomach stump's cancer most frequently. Authors preclude the postgastrectomy patients (II. type especially) are a group of cancer's risk in stomach stump, and are recommended to be covered with the out-patient care. The appropriate findings are compared to those of worldwide literary sources. PMID- 2263907 TI - [Conditions imitating malignant diseases of the female breast]. AB - In spite of eminent position of mammary carcinoma as to its diagnosis and treatment in literature sources on mammary diseases, the benign diseases of this location are evidenced unless 3 times as frequent. Uncommon benign lesions of female mammary gland are reported through the period of 3 years. Differential diagnosis misinterpretations are emphasized which may occur even at well equipped institutions. Surgery and detailed histological examinations showed the final character of lesions. Of importance also is the provision of dispensary care. Factors listed which augment the biological capability of malignant reversal. PMID- 2263906 TI - [An antireflux modification in gastric resection as a prevention for alkaline reflux]. AB - The alkaline duodenal or intestinal reflux of contents back to the stomach or postgastrectomy stump is known to result in chronic atrophic gastritis. In accord to several authors, it implies significantly the initiation of carcinoma of postgastrectomy stump. Authors of the present work referred to their routinely provided antirefluent modifications of Roux-en-Y gastrojejunoanastomosis in patients indicated to gastrectomy. Technically important steps of operation have been also reported. The 22-membered total of patients was presented with postsurgery revision results 3 to 36 month postoperatively. The operation mentioned was in accord with preventive DGR query. Remotely, the operation effectiveness should be evaluated as to the prevention of malignancy onset in postgastrectomy stump. PMID- 2263908 TI - [Screening using Krypto-Haem-SSWR for the early detection of colorectal carcinomas and adenomas]. AB - In the last 30 years, colorectal carcinomas have been stated to occur markedly in all industrial countries. From colonic and rectal malignant tumors, the amounts of 4225 in 1961 and 7220 in 1984 were newly registered in GDR. Thus the number of patients with colorectal carcinomas showed the decrease for up to 70.9% starting from 1961. The biochemical Krypto-Haem-SSWR screening test has been implemented during the last few years by members of proctologic section. Colorectal carcinoma was stated in 48 asymptomatic subjects aged more than 45 years, and colonic adenoma in 83, respectively. At present, the yearly screening of occult bleeding into faeces is the unique measure contributing to early recognition of colorectal carcinomas and precancerous lesions. PMID- 2263909 TI - [Polyps in the rectosigmoid]. AB - A total of rectosigmoidal adenomatous polyps from 1965 to 1987 is scrutinized. Authors refer to 1564 rectosigmoidal adenomas they diagnosed during the 23 years all along with transanal both surgery and endoscopy removal as well as subsequent histology. Patients are life-long submitted to regular rectoscopies, the adenomas being the initiation of adenocarcinomatous transformation. PMID- 2263910 TI - [Early diagnosis and treatment of small rectal carcinomas]. AB - After a brief review of literary sources, a total of 145 patients with average age 64.5 years is evaluated. Authors report on that the early diagnosed rectal carcinoma (T of Dukes A or CSI + II in accord with Mason) can be removed within the intact tissue either by transanal route or using the posterior proctotomy. The surgery-related mortality is of 0 per cent, the 10-year criterion recovery reaching up to 90%. PMID- 2263911 TI - [Sacral anesthesia in proctology]. AB - The experience with sacral anesthesia is reported on a total of 513 proctologic patients. From them, 105 cases were submitted to the sacral anesthesia without extradural morphine application, and 308 cases were anesthesized with simultaneous extradural administration of morphine. Easy in applicability, the sacral anesthesia is such an analgesic procedure which results in no complications and may be employed mainly in elder patients. The anesthetics prolonged in action (those similar in type with Bupivacain, Marcain) together with extradural morphine administration are also effective in respect with postoperative analgesia. An average time of postoperative analgesia represents 53 +/- 23.4 hrs. when 2 mg/kg Bupivacain, 0005% Epinephrine and 5 mg Morphinum hydrochloricum are applied, respectively. PMID- 2263912 TI - [Late results of esophageal prostheses created from intestinal grafts]. AB - During the last 30 years, 280 retrosternal esophageal replacements from stem intestinal grafts were performed at GIT Surgery Clinic AM in Wroclav. Both clinical and auxiliary investigations showed the small intestine grafts have been of the best function as to the food passage. In esophagi made from the large intestine, the following and mostly frequent changes occur: the dilatations of their lumina, the stop of food passage and inflammatory changes varying in both the degree and extent. Inflammatory changes as well as ulcers are rather difficult to detect by radiology. Through the last years, the Second Clinic of General Surgery AM in Wroclav provides endoscopy of artificial esophagi. Being sophisticated, this approach is of benefit in early determining pathologic changes in the esophageal wall, the collection of contents for biochemical tests, tissue biopsies for histology and the initiation of appropriate therapy. PMID- 2263913 TI - [Treatment of diffuse suppurative peritonitis by laparostomy]. PMID- 2263914 TI - [Chronic appendicitis in children]. AB - Starting from 1976 to 1983, a total of 114 children was submitted to surgery for chronic appendicitis. The 5 to 13 years postappendectomy results were evaluated in 105 patients. From them, 68 (64.8%) were without complaints, 27 (25.7%) showed the substantial improvement. Of any favourable effect were 3 postappendectomy children, i.e. 2.8%. In one case, a serious postoperative complication occurred, this resulting in the small intestine strangulative ileus 2 mos. after the appendectomy. Different and even contradictory views are discussed in regard with the properly existence, signs, diagnosis and management of chronic appendicitis. The authors estimate chronic appendicitis to be the clinical and by no means the pathologico-anatomical diagnosis. According to them, the children are indicated to the elective appendectomy after preliminary investigation which is focused on the exclusion of other serious diseases similar in subjective complaints. PMID- 2263915 TI - [Surgical reconstruction of long esophageal stenoses in children]. AB - Four cases related with the long stenosis of lower part of esophagus are referred to in children. These were stenoses of fibromuscular type, due to achalasia and resulting from etching with sulphuric acid as well as from tumor. The extramucous myotomy, esophagotomy and colonic replacement of long esophageal stenosis were elected. The condition is repairable by esophagomyotomy or esophagotomy when the function of stenotic portion of esophagus is preserved. To prevent postoperative complications such as fistula, diverticulum, gastroesophageal reflux and restenosis, the covering of incision with a patch from gastric fundus is recommended with subsequent fundoplication. Anatomical and functional lesion of esophageal wall in the presence of long stenosis requires its esophagoplasty as well as replacement with the intestinal interposition. PMID- 2263917 TI - Swedish Association of Urology. Proceedings of the spring meeting 1988 and the annual meeting 1988. Stockholm, May 26-27, 1988 and Stockholm, November 29 December 2, 1988. Abstracts. PMID- 2263916 TI - [Abdominal actinomycosis in children]. AB - A total of four children (1 female and 3 male subjects aged from 3.5 to 10 years) is reported as treated by surgery and antibiotics for the abdominal focus of actinomycosis. The infection was manifested as an infiltration around the inflamed appendix in one case, the second case was related with multiple infiltrations in the abdominal wall and pelvic region. Two patients showed cyst and eventually urachal sinus infiltrated with actinomycosis. The diagnosis was determined in all cases from histology. In three cases, the inflammatory tumor was exstirpated in toto. The treatment with penicillin combined with streptomycin or other antibiotic has lasted no longer than 6, 28, 29 and 80 days, respectively. The emphasis is made on the benefit of resectional surgery which reduces the amount of antibiotics needed and shortens the therapeutic course of actinomycosis. PMID- 2263918 TI - Effects of prolonged muscle stretch on reflex and voluntary muscle activations in children with spastic cerebral palsy. AB - We studied the short term effects of a single session of prolonged muscle stretch (PMS) on reflex and voluntary muscle activations in 22 children with spastic cerebral palsy (CP) assigned to an experimental (n = 12) and a control group (n = 10). Children of the experimental group underwent PMS of the triceps surae (TS) by standing with the feet dorsiflexed on a tilt-table for 30 min, whereas children of the control group were kept at rest. The effects were determined by measuring the associated changes in torque and in electromyographic (EMG) activity of the TS and tibialis anterior (TA) muscles during both passive ankle movements and maximal static voluntary contractions. The results indicate that PMS led to reduced spasticity in ankle muscles as demonstrated by the significant reductions (p less than 0.05) of the neuromuscular responses (torque and EMG) to passive movement. These inhibitory effects lasted up to 35 min after cessation of PMS. In addition, the capacity to voluntarily activate the plantar flexors was significantly (p less than 0.05) increased post-PMS, but the capacity to activate the dorsiflexors was apparently not affected. These findings suggest that repeated sessions of PMS may have beneficial effects in the management of spasticity in children with CP. PMID- 2263919 TI - Pulsed ultrasound does not improve healing of venous ulcers. AB - A controlled study of the effects of pulsed ultrasound was carried out in conjunction with a standard treatment for healing chronic leg ulcers on 44 patients divided randomly into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) plus placebo-ultrasound or pulsed ultrasound (1:9, 0.5 watt/cm2 at 1 MHz, for 10 min) 3 days a week for 4 weeks, thereafter twice weekly for 4 weeks and once weekly for the following 4 weeks. Percentage healed ulcer area and comparison of percentage healed ulcers were examined after 4, 8 and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the pulsed ultrasound group as compared with the placebo group. PMID- 2263920 TI - Effect of pulsed ultrasound versus placebo on muscle soreness perception and muscular performance. AB - The purpose of this study was to compare the analgesic effect of pulsating ultrasound treatment and placebo on delayed onset of muscle soreness produced by an eccentric exercise bout. In addition, the effect of pulsed ultrasound on muscular performance following an eccentric exercise bout was studied. Eighteen untrained subjects were randomly assigned to: 1) ultrasound (A) [N = 6] over the areas of concentrated muscle soreness, i.e. proximal vastus lateralis and distal vastus medialis; 2) placebo ultrasound (B) [N = 6]; and 3) no therapeutic intervention (C) [N = 6]. Baseline data were recorded for maximum isometric knee extension contraction (MVC), maximum knee extension torque (MT), knee extension work (W), and soreness perception (SP). All values were subsequently reassessed 24 and 48 hours after intense muscular activity. Immediately following the 24 hour reassessment the A group received ultrasound treatment, the B group received placebo ultrasound, while the C group received no treatment. Percent deviation from baseline of SP, MVC, MT and W were significantly less for A than B and C (p less than 0.05) at 48 hours post muscle soreness bout. These data indicate that pulsed ultrasound accelerates restoration of normal muscle performance, and thus is effective in decreasing delayed onset of muscle soreness. The mechanism for decreasing soreness perception in the muscle is unknown, but may be related to decreasing intramuscular pressure and/or decreasing the inflammatory response. PMID- 2263921 TI - Group training in parkinsonism: quantitative measurements of treatment. AB - Ten patients with mild to moderate parkinsonism were tested before and after a 12 week training program. Strength was tested with simultaneous EMG registration in the ankle flexors at different angular velocities using a modified Cybex II equipment. Peak Torque (pT), Torque area (Ta) and Emg area (iEMGa) for the eccentric and concentric contractions were calculated. Quotients-q (Ta)/(iEMG) for evaluation of work per iEMG in concentric and eccentric contractions were calculated. Gait analysis and a questionnaire for evaluation of the functional level were also included. Mean peak torque values did not change with training. Concentric quotients-q between test one and control was significantly lower in 30 degrees/s and 120 degrees/s; eccentric quotient-q was significantly lower in the same velocities but between test 2 and control. No improvement in gait was found. Patient questionnaire ratings did not improve significantly though patients had an overall impression of a beneficial effect of physical therapy. No long term effect was found. The results showed with the measuring methods presented no consistent measurable effect from group training in Parkinson's disease. PMID- 2263922 TI - [Pathophysiology of heart insufficiency]. AB - Chronic heart failure is characterized by the inability of the heart to pump the blood at a rate commensurate with the requirements of the peripheral organs at rest and under exercise conditions. The most common cause of heart failure is coronary artery disease, followed by hypertensive, valvular and myocardial heart disease. Different forms of chronic heart failure have been described (acute and chronic heart failure, forward and backward failure, right and left heart failure, systolic pump and diastolic compliance failure, etc.). The compensatory mechanisms in heart failure are related to hemodynamic and structural as well as metabolic and neurohumoral changes. Prognosis of chronic heart failure is usually poor and the annual mortality rate ranges between 20 and 50% depending on the degree of functional impairment. PMID- 2263923 TI - [The treatment of acute severe cardiac insufficiency]. AB - The clinical syndrome of severe acute heart failure may be caused by several distinct mechanisms. Some of these require a specific approach in addition to general measures, and prompt diagnosis is thus of great importance in order to define the initial and long-term therapeutic targets. This review recalls the basic principles of differential diagnosis and pharmacological treatment. The logistics of diagnosis and treatment inside the hospital are also discussed. The respective uses of mechanical ventilation, intraaortic balloon counterpulsation and ventricular assist devices are outlined. PMID- 2263924 TI - [Computer-assisted drug information]. AB - Experience with a university hospital based drug information service (DIS) is reported. A total of 501 drug related questions were analyzed during two prospective evaluation periods of 13 and 14 months' duration respectively. Information was requested by physicians and pharmacists chiefly on practical aspects of drug treatment in individual patients (77%), such as drug choice, dosage adaptation, side effects and interactions. Inquiries on drug safety in pregnancy and lactation (8.8%), and questions on pharmaceutical properties (14.2%), including pharmacokinetics, were also frequent. Our experience indicates that a problem-oriented, comprehensive DIS necessitates close cooperation between physicians trained in clinical pharmacology and pharmacists within the same team. The use of electronic media greatly facilitates the collection of drug related information, data retrieval and storage. Drug information services can contribute to improved quality and safety of drug therapy. PMID- 2263925 TI - Semi-quantitative simulation for reasoning about physiological models of drug kinetics and effects. AB - Inter- and intra-individual pharmacokinetic or pharmacodynamic variability is a major cause of adverse drug reactions or ineffective therapy. We are developing a computer-based tool for predicting the consequences of different physiological and pathological states and for reasoning about the possible causes of observed variability that may be useful both in a clinical decision support environment for drug monitoring and as a research aid in the investigation of the influence of physiological factors on drug response. It is based on a physiological approach to pharmacokinetic modeling in which actual anatomical or physiological entities, such as organs, tissues or blood flows, are represented. These models serve as the basis for semi-quantitative simulation, a method linking classical quantitative simulation (by numerical integration of differential equations) with artificial intelligence-based qualitative simulation techniques. This approach retains the mathematical power of the Systems Dynamics method for solving complex, time-varying systems containing feed-back loops, which are intractable for current qualitative knowledge representation techniques, and extends it with the causal reasoning and explanation power of symbolic inference techniques used in expert systems. It also allows problem solving in situations, so common in medicine, where initial values of variables and parameters cannot be estimated precisely. Simulation outputs are intended to be qualitatively, but not necessarily quantitatively, correct. The semi-quantitative simulation method was originally developed in MacLisp on a DEC 2060 and applied to modeling cardio vascular physiology. We are porting the code to Common Lisp on a Macintosh and adapting the approach to pharmacology, concentrating on drug metabolism issues, with lidocaine pharmacokinetics as a test case. PMID- 2263926 TI - [Immuno-allergic interstitial nephritis: steroids yes or no?]. AB - Clinical decision analysis computer programs are now being developed and can guide the physician facing difficult options. The clinical example chosen here is that of a 58-year-old patient with acute interstitial nephritis, and the question to be answered is: are steroids indicated? The result suggests that, in view of the high mortality associated with dialysis, a trial with steroids is warranted. PMID- 2263928 TI - [New architectures destined for hospital computer networks opening the medical world to more communication facilities of every kind]. AB - It is sound medical education discipline to ask for a review of the literature, patient to patient, before setting up any global appraisal or clinical judgement. Next it appears legitimate to conduct similar searches with a local or institutional data base management system to find similar local patients to be compared with those of the literature. Both actions need communication facilities to be rooted in the patient ward unit. It is shown how well the new workstations are suited to these communication expectancies, with an appropriate capability of providing a user-friendly human interface, international bibliographical research (such as MEDLINE), a remote computer assisted learning programme library, image manipulation and local medical records handling. It is also emphasized that the expectancies related to UMLS (Unified Medical Language System of the National Library of Medicine in Washington DC) or to telemedicine are closely dependent on the availability of the high networking performances now available. PMID- 2263927 TI - From biopsy to automatic diagnosis. AB - High resolution two-dimensional gel electrophoresis is a very powerful biochemical tool for analysis of complex protein mixtures. In well defined situations, protein maps, obtained from tissue biopsies or biological fluids by this technique, can be automatically analyzed by computer. Some polypeptide patterns are the fingerprints of diseases. Applying clustering algorithm and learning techniques, the prototype expert system MELANIE recognized patterns and associated the correct diagnosis to the specific pattern. PMID- 2263929 TI - [Registration of detailed data in the medical record or how to translate "impressions" into measurable observations]. AB - Every medical case record represents a mass of data (texts, pictures, figures, etc.) in an unstructured form. The physician needs to retrieve this data via several access routes: temporal (dependent on date or sequences of events), type of data (diagnostic, treatment, clinical signs, laboratory findings, image descriptors, all with their interrelationships), or depending on the severity of the disease, etc. Retrieval of this data fulfils several functions: circulation of a case record among specialists, assistance in summarizing a long and complex clinical course, comparison of patients, research, and teaching. Three projects are described which have the same aim: structuring of the case record in order to retrieve detailed data on patients as individuals and describe clinical courses on the basis of measurable observations. This structure must be understandable to a computer (directly or indirectly) so that searches and comparisons can be performed automatically. The first project, entitled "indexed paragraph prototype" reproduces the structure of the problem-oriented case record and is designed to input the Medical Outpatients Department's follow-up notes into the computer. The second, "automatic language analysis", aims to exploit two characteristics of medical language, its omnipresence in the case record and its reliability, in view of its status as the spontaneous vehicle of communication between physicians. The third, "collection of clinical signs during consultation", is based on a prospective collection of all elements of clinical observation, structured temporally consultation by consultation. The purpose of precise collection of detailed and measurable observations in individual patients is to identify those among the clinical signs which display the greatest power of discrimination, i.e. those which best serve to predict the case's evolution. PMID- 2263930 TI - [Comparison of 2 series of autopsies observed at Johns-Hopkins Medical Center, Baltimore (JHMI) and at the Neuchatel Institute of Pathology (INAP)]. AB - We are reporting the first results of a comparative study of 100 consecutive autopsies and their clinical diagnoses, observed at the Johns Hopkins Medical Institutions (JHMI) and at the Institut neuchatelois d'anatomie pathologique (INAP). The diagnoses of the two series were coded according to the two different systems used currently at the two institutions. The data from Baltimore were automatically classified by a special "key word method" using the categories of the Index Medicus (MeSH = Medical subject headings). We proceeded then to a second recording by SNOMED codes, introduced into the computer system in the same way as we document the autopsy diagnoses in Neuchatel. The two series could be compared in detail according to topographical, morphological and aetiological parameters. The over-all repartition of the examined cases shows a higher incidence of newborns in Baltimore (23), in Neuchatel we observed only 7 newborn autopsies. The mean age was inferior in Baltimore (males: 53.5 years for JHMI, 73.1 years for INAP; females: 58.4 years for JHMI, 66.2 years for INAP). The number of diagnoses per autopsy was 31.9 at JHMI, and 50.1 in Neuchatel. The topographical distribution of clinical and autopsy diagnoses showed a higher frequency of central nervous system lesions in JHMI which might be explained by the activity of a neuropathological division. Findings concerning the morphological categories revealed a higher frequency in JHMI for traumatic abnormalities (7.2% vs 2.5%), malformations (4.3% vs 0.8%), whereas inflammation and fibrosis and degenerative lesions were more often encountered in Neuchatel. The differences in morphological observations could be attributed to a higher proportion of newborn cases in JHMI with complex malformation syndromes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263932 TI - [The enduring topic of lateral dental fillings]. PMID- 2263931 TI - [Blood pressure monitoring in aged hypertensive patients treated with sustained release nicardipine or nifedipine]. AB - In a double-blind parallel study, 20 elderly hypertensive subjects (mean age 85 years) were treated either by nicardipine or by nifedipine in slow-release form for 7 days. Blood pressure was measured by ambulatory, non-invasive daytime monitoring. Efficacy of both drugs was similar on the seventh day of treatment. However, the hypotensive effect induced by nifedipine was maximal on the first day of treatment, in contrast to the progressive effect induced by nicardipine. In 2 cases, marked hypotension was observed after the first tablet of nifedipine. PMID- 2263933 TI - [The wear on enamel, amalgam and their enamel antagonists in a computer controlled mastication simulator]. AB - In a long-term in-vitro test the wear of enamel fossae, amalgam restorations and their opposing enamel cusps in the occlusal contact area was evaluated, qualitatively and quantitatively. The wear of enamel cusps differed from the wear of enamel fossae. The amalgam restorations wore down more rapidly than enamel fossae, but they were less destructive against their opposing enamel cusps. The wear of all tested materials was not linear. The results will serve as reference data for future long-term in-vitro tests of posterior restorative materials. PMID- 2263935 TI - [Cremation and the environmental mercury burden]. AB - The dental status of 130 deceased Zurich people was evaluated from radiographs of their maxillary and mandibular dentitions taken during their autopsies. A mean mass of mercury of 2.49 +/- 0.37 g was calculated per dentate deceased based on the analysis of 134 extracted premolars and molars with amalgam restorations. The mercury contamination due to cremation in 1988 in Switzerland was calculated to vary between 45.8 and 79.0 kg, based on both the data from the sample analyzed and the fact that 55.5% of Swiss funerals were cremations, the average age of death was 73 and that 70% of the people of that age retained some of their teeth. Mercury contamination by cremation, therefore comprised only 0.61 to 1.53% of the total mercury contamination produced by all waste incineration methods. The minimal contribution to the mercury contamination due to cremation can thus not be used as an argument to ban the use of dental amalgams. PMID- 2263934 TI - [Mercury loading from amalgam fillings]. AB - Recently, the dental filling material amalgam has again been a target of criticism, especially within the mass media. The controversy has been further fueled by the combination of the patients' desire for fillings to match tooth colouring and this latest wave of artificially created fear of the poison mercury. The investigation submitted here is seen as a contribution toward clearing up the issue of any risk. Using flameless atom absorption spectroscopy, blood and urine samples were taken from four test groups and examined for their mercury content. Two of the participating groups tested (dentists and assistants) were actively processing mercury while the other two, one with and one without amalgam fillings, served as control groups. In the daily preparation of amalgam, dental staff working in the dental office were subject to greater exposure to mercury vapours. Their blood readings, therefore, were double those of the control group, while their urine readings were much higher than those for people not working with mercury. The two control groups (with and without amalgam fillings) showed no significant difference in mercury levels, which implies that these slight traces of mercury can be attributed to food and the environment. Although the mercury readings of the dental office personnel were twice as high as that of the control group, there was no threat of mercury poisoning for any of the four groups. The continued use of amalgam fillings in teeth can be recommended without reservation and at no risk to the patient. Particular measures must be taken to guarantee the safety of office staff. PMID- 2263936 TI - [The marginal accuracy of the fit of fixed adhesive ceramic inlays]. AB - 48 extracted human molars were restored with MOD inlays using 3 different ceramic systems: Dicor, Mirage and Vitadur N. For the Dicor system both the direct and indirect manufacturing procedures were used and all the necessary technical and clinical steps were performed. After being subjected to a thermal cycling stress test for 100 days, the teeth were ground sectioned for light microscopic examination. Sintered high-strength ceramic systems (Mirage and Vitadur N) displayed significantly better marginal adaptation than casted glass ceramic. In order to estimate the extent of the outer marginal gap, we measured the defective surface where the adhesive composite had disintegrated. The best possible marginal fit will certainly prolong the longevity of inlay restorations. PMID- 2263937 TI - [Restorations of posterior teeth. What choice?]. PMID- 2263938 TI - [Restoration with composite inlays. Amalgam substitute: restoration using a direct immediate inlay made of composite]. PMID- 2263939 TI - [Porcelain inlays as an amalgam substitute? A report on the experience after 5 years of clinical use]. PMID- 2263940 TI - [Perioprosthodontics (II)]. PMID- 2263942 TI - [Order in the world is but an appearance]. PMID- 2263941 TI - [The SSO public survey. The attitude of the Swiss towards the dentist in 1990. Societe Suisse d'Odonto-Stomatologie]. PMID- 2263944 TI - [The feedback proves it: the CS (Commission scientifique) is on the right path. Interview by Kurt Venner]. PMID- 2263943 TI - ["The SSO should be more concerned with junior members". Societe Suisse d'Odonto Stomatologie. Interview by Kurt Venner]. PMID- 2263945 TI - [Was is "indicated"?]. PMID- 2263946 TI - [On the 75th anniversary of the Solothurn Dental Society]. PMID- 2263947 TI - ["Tooth-colored inlays"]. PMID- 2263948 TI - [School dental care: the conscientious and careful work of dentists is indispensable]. PMID- 2263949 TI - Recognition for following traditional roles. PMID- 2263950 TI - Thyroid hormone replacement: indications, dosage, and monitoring. PMID- 2263951 TI - Practical alternatives to homologous blood transfusions. PMID- 2263952 TI - Teaming up for diabetes education. AB - Education is a key component in living well with diabetes. Successful management of diabetes is enhanced by a team effort that involves the physician working collaboratively with the patient and informed and concerned health professionals. This article shares insights into the diabetes education process from the perspective of various team members. PMID- 2263953 TI - Superior mesenteric artery syndrome: an approach to the diagnosis and management of upper gastrointestinal obstruction of unclear etiology. AB - The differential diagnosis of upper intestinal obstruction includes mechanical obstruction, obstruction secondary to systemic disease, and idiopathic intestinal pseudo-obstruction. The causes of these are extensive; however, the majority of cases involve a mechanical etiology. Superior mesenteric artery syndrome (SMAS) is a rare and controversial form of mechanical obstruction with just over 300 well-defined cases described in literature. The diagnosis is often difficult to establish, even after surgery. In addition, this syndrome sometimes may be managed conservatively, leaving a definitive diagnosis unproven. A case of SMAS and a description of the syndrome is presented. The patient was managed conservatively and recovered without difficulty. One of the most difficult diseases to differentiate from SMAS is megaduodenum (intestinal pseudo obstruction localized to the duodenum). Both entities present as obstruction with an unclear etiology. A reasonable approach to the diagnosis and management of upper intestinal obstruction (including figures, tables, and an algorithm), with emphasis on the above two diseases, is discussed. PMID- 2263954 TI - [Changes in systolic and diastolic function of reperfused myocardium after short coronary occlusions in conscious dogs]. AB - Mongrel dogs were chronically implanted with sonomicrometer crystals and a high fidelity tip micromanometer to measure ventricular wall thickness (WT) and left ventricular pressure (LVP), respectively. Two weeks after surgical operation, the left circumflex coronary artery was occluded with a hydraulic occluder for 3 minutes in conscious condition. During reperfusion, the hemodynamic parameters and systolic wall thickening recovered to the normal level quickly, while an abnormal thickening phase during early relaxation (extra phase) appeared in the dWT/dt-WT loop (X-axis = WT, Y-axis = dWT/dt) with its pattern different from that during control and ischemic conditions. This kind of pattern of the loop could be observed during hypoxia and during rapid overfilling of coronary artery. It is supposed that some substances, which may be produced in the ischemic myocardium, induced an extra dilation of coronary artery during reperfusion and a rapid overperfusion in the early relaxation phase of the cardiac cycle, leading to the abnormal pattern in the loop. PMID- 2263955 TI - [Effect of scopolamine and picrotoxin on the learning-dependent long-term synaptic potentiation]. AB - The purpose of this study was to investigate the effects of microinjection of scopolamine, a M-cholinergic antagonist and picrotoxin, a GABA-ergic antagonist into the rat hippocampal CA3 area on the learning-dependent long-term potentiation (LDLTP) during the establishment, extinction and re-establishment of conditioned drinking response. Following stimulation of the perforant path, field potentials of hippocampal CA3 of freely moving rats were recorded. The results were as follows: the synaptic efficacy and the development of LDLTP in hippocampal CA3 were depressed significantly by scopolamine, but the extinction of LDLTP was accelerated. Picrotoxin significantly enhanced synaptic efficacy and facilitated the development of LDLTP, but it depressed the extinction of LDLTP. Meanwhile, the establishment or extinction of drinking conditioning was correspondingly depressed or accelerated. Moreover, the development of LDLTP and its extinction preceded the development and extinction of drinking conditioning. The results provide further evidence indicating that LDLTP might be one of the neuronal mechanisms underlying behavioral learning and memory. Moreover, it seems that M-cholinergic receptors and GABA-ergic receptors in rat hippocampal CA3 area are involved in the development and retention of LDLTP. PMID- 2263956 TI - [A study on location of vocalization centres in hawfinch (Coccothraustes coccothraustes)]. AB - Vocal-control nuclei in hawfinch (Coccothraustes coccothraustes) were studied by HRP retrograde tracing and electrophysiological methods. Vocal control centres in hawfinch consist of four discrete nuclei. Hyperstriatum ventral, pars caudale (HVc) is the highest nucleus, with its efferent fibers projecting to the rubust nucleus of archistriatum (RA), which in turn projects to the nucleus intercollicularis (ICo) of midbrain and the nucleus intermedius (IM) of medulla oblongata IM innervating vocal organ (syrinx) also receives input from ICo. The both vocal control pathways are not strictly unilateral. ICo plays a relative independent role in vocal control. The stereotaxic coordinates for HVc RA, ICo, IM are tabulated in Table 2. PMID- 2263957 TI - [Effects of indomethacin on 45Ca uptake and membrane fluidity of mitochondria and microsomes from rat liver]. AB - We have reported previously that indomethacin-pretreatment could induce marked hepatic protection in rats. The present work reported effects of indomethacin on calcium regulation and membrane fluidity of mitochondria and microsomes of hepatocytes. The results showed that calcium uptake and membrane fluidity increased significantly in mitochondria and microsomes of hepatocytes isolated from the rats pretreated with indomethacin in vivo as compared with that from the control; adding indomethacin directly to isolated mitochondria and microsomes from normal rats in vitro, on the contrary, decreased membrane fluidity. These changes may be related to the protective effect of indomethacin. PMID- 2263958 TI - [Effects of recombinant erythropoietin on terminal cytoplasmic maturation of megakaryocytes and thrombopoiesis]. AB - The liquid culture system of platelet production was used to monitor the effect of recombinant human erythropoietin (r-EPO) on megakaryocyte maturation and thrombopoiesis. r-EPO, when added to the culture at concentration from 1U/ml to 6U/ml, significantly increased the platelet count in a dose dependent manner, while the megakaryocyte number remained unchanged. The rate of cytoplasmic maturation and DNA synthesis of megakaryocyte were increased by r-EPO. Our data indicate that r-EPO is a potent stimulant for terminal cytoplasmic maturation of megakaryocyte and thrombopoiesis. PMID- 2263959 TI - [Stimulation of megakaryocyte maturation and thrombopoiesis in vitro by thrombocytopoiesis-stimulating factor]. AB - The liquid culture system with platelet production was used to investigate the effects of thrombocytopoiesis-stimulating factor (TSF) on terminal cytoplasmic maturation of megakaryocyte and thrombopoiesis. TSF, at concentrations from 0.5 2.0 U/ml, stimulated megakaryocyte DNA synthesis, cytoplasmic maturation and isotopic incorporation into platelets, whereas megakaryocyte and platelet count remained unchanged. Our data indicate that TSF, stimulates platelet production by increasing the size of platelet. PMID- 2263960 TI - [Effect of the overactivated central renin-angiotensin system on the concentration of brain norepinephrine and epinephrine in stroke-prone spontaneously hypertensive rats and its significances]. AB - The content of norepinephrine (NE) and epinephrine (E) in the brain of spontaneously hypertensive rats has proved abnormal, but the cause remained unknown. It was shown in the recent work that NE content in pons, posterior hypothalamus, nucleus caudatus and E concentration in medulla oblongata, anterior and posterior hypothalamus of 12-week old stroke-prone spontaneously hypertensive rats (SHRSP) were much higher than those of age-matched Wister-Kyoto rats (WKY). SHRSP also showed higher levels of systolic blood pressure (SBP) and brain angiotensin II (A II) than WKY. Intracerebroventricular (icv) perfusion of angiotensin-converting enzyme inhibitor captopril (20 micrograms for each time and three times for each day for four weeks) inhibited the synthesis of brain A II and reduced SBP and NE, E contents in all examined brain areas in SHRSP and WKY. However, the effects of chronically perfused captopril on SBP and brain NE, E levels in SHRSP were much more significant than in WKY. The results indicate that the modulatory effects of central renin-angiotensin system (RAS) on central adrenergic and noradrenergic system might be overactivated in SHRSP, which might partially responsible for the abnormally high levels of NE, E in some of the brain areas of SHRSP. PMID- 2263961 TI - [Potentiating effect of L-tetrahydropalmatine on the suppression of cortical tooth-pulp evoked potentials by electroacupuncture in rabbits]. AB - Cortical potentials evoked by stimulation of the contralateral tooth-pulp were recorded epidurally from the SI cortex of rabbits anesthetized with urethane and chloralose. It was found that nociceptive components of the evoked potential consisted of P1 and P2 wavelets with a relative stable peak latency of 22.5 +/- 1.2 ms and 66.1 +/- 1.9 ms respectively. Higher intensity of tooth pulp stimulation was required for appearance of P2 than P1. Diazepam, a non-analgesic sedative, reduced P1 but not P2 amplitude. On the contrary, dolantin, an analgesic, suppressed P2 but showed no significant influence on P1. The results suggest that P2, but not P1 might be related to pain. The effects of l tetrahydropalmatine (1-THP) and electroacupuncture on P2 were observed on 12 animals. The results showed that both iv l-THP 8mg/kg and electroacupuncture brought forth a decrease in P2 amplitude by 40.3 +/- 14% and 59.3 +/- 10% respectively, while electroacupuncture combined with l-THP produce a further decrease in P2 amplitude by 92.8 +/- 7%. Furthermore, the inhibitory periods of P2 amplitude were significantly prolonged after electroacupuncture combined with l-THP. The results indicated that l-THP enhanced the suppression of P2 by electroacupuncture. PMID- 2263962 TI - [The comparison of the binding of Ru486 to progesterone receptor of pituitary and endometrium in ovariectomized rat]. AB - Following intramuscular injections of increasing doses of Ru486 (0.1 mg/kg-2 mg/kg), free progesterone binding sites remaining in pituitary and endometrium in estrogen-primed OVX rats decreased. Thirty minutes after administration of Ru486 (2 mg/kg) the binding sites of progesterone receptor in both tissues showed a significant initial decrease, and then gradually reached the lowest level in 2 h. Afterwards the levels of progesterone receptor began to increase. The results suggested that Ru486 could interact with progesterone receptor in both tissues. However, the binding ability of Ru486 for different tissue was not exactly the same, and Ru486 binding to the progesterone receptor in endometrium might be easier. PMID- 2263963 TI - Cervical spinal canal plasticity in children as determined by the vertebral body ratio technique. AB - The sagittal cervical canal measurement from a plain spine radiography is easy to obtain and has a smaller range than the interpedicular distance. In an effort to standardize the sagittal measurement, a canal ratio, using the vertebral body diameter, has been formulated. If this method is to be used in the pediatric spine, the effect of the growing neuraxis must be considered. Lateral cervical spine radiographs of 301 normal children and adults were evaluated and grouped according to age. The canal ratio measurement demonstrated a consistent decrease through to the adult groups. Adjacent groups showed statistically significant decreases with age in all groups tested other than the oldest two groups. With the pediatric spinal canal vulnerable to various intracanalicular influences, the canal ratio may reflect early disease processes. PMID- 2263964 TI - Cervical muscle myoelectric response to acute experimental sternocleidomastoid pain. AB - A method is presented for investigating the response of passive and active muscle to experimentally induced deep muscle pain. Ten healthy adult males performed multiple, submaximal isometric neck flexion tasks before and after pain had been induced in the sternocleidomastoid (SCM) muscle by injecting 5 ml of a hypertonic (5%) saline solution. A similar volume of isotonic saline was injected into the contralateral muscle as a control. Cervical myoelectric signal (MES) root-mean square (RMS) response to each injection was recorded from eight neck muscles over 8 minutes. The subject rated perceived pain at regular intervals using a visual analog scale (VAS). Sternocleidomastoid pain, which reached a mean of 36 mm on the 100-mm VAS 2 minutes after the injection, resulted in significantly increased (1-2 microV, P less than 0.05) RMS MES in the otherwise relaxed SCM muscle during the first 2 minutes. This was followed by a gradual return to control values after 5 minutes. A similar trend in MES was found for the active SCM muscle during a 10% maximum voluntary contraction (MVC) isometric neck flexion effort. Thus, acute deep muscle pain caused subtle, yet systematic, changes in motor output in both the relaxed and active painful muscle, and its synergists and antagonists. PMID- 2263965 TI - Motor-evoked potentials in patients with cervical spine disorders. AB - Measurements of motor-evoked potentials by means of fractionated magnetic stimulation of motor pathways to the upper limbs was performed as part of the clinical assessment in 268 patients with cervical spine disorders. Seventy-two percent of the 127 patients with degenerative changes of the cervical spine, 67% of the 55 patients with rheumatoid arthritis (RA), and 57% of the 51 patients with trauma of the cervical spine showed a pathologic delay of central motor latency (CML). The data suggest that this method has a high sensitivity and therefore is recommended in the diagnosis of cervical spine disorders in patients with suspected compression of neural structures. PMID- 2263966 TI - Anterior cervical discectomy and fusion. AB - A retrospective review of 94 patients who had undergone anterior cervical discectomy and fusion was performed to analyze the result in patients who had a diagnosis of posterolateral spondylosis, disc herniation, or both. Although in 23 of 94 patients additional adjacent asymptomatic levels of spondylosis were noted, only the symptomatic levels were addressed in the 94 cases. Postoperatively two cases of dysphagia were noted, as well as a 4% pseudarthrosis rate. There was an 88% good or excellent result when no additional spondylosis was present, but only a 60% good or excellent result when just the symptomatic levels were addressed, leaving unoperated adjacent levels of spondylosis. PMID- 2263967 TI - Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. AB - Anterior cervical fusion was initially described in the 1950s for cervical spondylotic radiculopathy. The indications for this procedure in the management of soft disc herniation have not been clearly defined. In addition, controversy exists as to whether a cervical soft herniation should be managed by an anterior approach or a posterior cervical laminotomy-foraminotomy. The authors report the results of a prospective study comparing anterior discectomy and fusion to posterior laminotomy-foraminotomy for the management of soft cervical disc herniation. Twenty-eight patients underwent anterior discectomy and fusion (Robinson horseshoe graft) while 16 patients underwent posterior laminotomy foraminotomy. The disc herniations were classified into two types. Type I were single level anterolateral herniations (33 patients) while type II were central soft disc herniations (11 patients). Clinically, patients with type I herniations manifested signs and symptoms of radiculopathy while patients with type II herniations manifested signs of myelopathy or neck pain and bilateral upper extremity paresthesias in 4 patients. Confirmatory studies were myelography in 12 patients, myelography combined with computed tomography (CT) in 26 patients, and magnetic resonance imaging (MRI) in 6 patients. For type I herniations, 17 patients underwent anterior fusion while 16 patients had a posterior laminotomy foraminotomy. The 11 patients classified as type II herniation all underwent anterior discectomy and fusion. There were 27 men and 17 women. The age range was 21 to 52 years (mean, 41 years). The follow-up was 1.6 to 8.2 years (mean, 4.2 years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263968 TI - Injury biomechanics of the human cervical column. AB - In this study, the authors have developed a technique to replicate clinically relevant traumatic cervical spine injuries and determined the injury biomechanics. Because of the importance of compressive forces in neck injuries, this research was conducted using compression as the primary load vector. Six fresh human cadaveric head-neck complexes were prepared by fixing the distal end in methylmethacrylate. Tests were done with varying loading rates to include quasistatic and dynamic conditions. For quasistatic experiments, the proximal end was fixed to the piston of the testing device. In dynamic tests, the cranium was unconstrained, and to maintain stability, the effects of the spinal musculature were simulated by means of pulleys, deadweights, and springs in the anterior and posterior parts of the head-neck complex. Quasistatic tests conducted at a rate of 2.0 mm/sec produced cervical spine trauma at forces ranging from 1.7 to 2.3 kN, with deformations ranging from 2.2 to 3.7 cm. The specimens were deep-frozen at the level of injury, preserving the local deformation of the tissues to enable a detailed evaluation immediately after the injury. Dynamic tests conducted at velocities of 3.2 to 5.7 m/sec resulted in impact injuries at one level of the head-neck complex. The applied forces at the vertex were considerably higher than those recorded at the distal end. The failure deformations for both the quasistatic (2.2-3.7 cm) and dynamic (1.7-3.2 cm) tests, however, were found to be similar, suggesting that the human head-neck complex is a deformation sensitive structure. PMID- 2263969 TI - Functional stability of the canine cervical spine after injury. A three-month in vivo study. AB - Although clinical instability is an in vivo problem, most spinal instability criteria are either subjective or are based on in vitro experiments. The authors performed an in vivo experiment using a canine model to study the natural history of spinal instability as a function of healing time up to 12 weeks. Three injuries were produced surgically: sham; laminectomy at C4; and bilateral facetectomy at C4-C5. Three 1.5-mm steel balls were implanted into C3 to C6 vertebrae at the time of surgery. Standardized functional flexion-extension stereoradiographs of the cervical spine were obtained before injury, immediately after injury and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7.5, 9, and 12 weeks postinjury and immediately after killing the animals. In general, the authors found decreased ranges of motion (ROM) at the C4-C5 level, compared with the pre-injury values, for all injuries, but most significantly for the facetectomy. The maximum decrease occurred between 0 and 0.5 weeks postinjury. Between 2 and 12 weeks, there was recovery in the ROM, especially for the two less severe injuries. The changes in the ROM at each spinal level were explained by simultaneous presence of a destabilizing factor, caused by the three different injuries with the sham as the least and the facetectomy as the most destabilizing injury, and a stabilizing mechanism of muscle spasm in the beginning and of healing and other adaptive responses in the late phase after injury. Because of the significant differences between the canine model and the human cervical spine, the present findings should be extrapolated to the human situation with caution. PMID- 2263970 TI - The injured canine cervical spine after six months of healing. An in vitro three dimensional study. AB - The cervical spine is a common site of spinal injuries. The stability of an injured cervical spine is not only dependent on injury severity, but also on the degree of healing time. Using a canine model, three injuries of varying degrees of severity were surgically produced at the C4-C5 level and allowed to heal for 6 months. No internal or external support was provided. The harvested cervical spines (C2-C7) were subjected to three-dimensional biomechanical testing by applying individually six pure moments. The resulting three-dimensional displacements were recorded using stereophotogrammetry, and the intervertebral motions were calculated. The results are compared with the in vivo behavior of the same specimens and with an in vitro control group. At 1 N-m, the average flexion-extension range of motion (ROM) for the intact C4-C5 level was 24.5 degrees (standard deviation [SD], 6.6 degrees). A facetectomy at this level significantly increased the in vitro ROM to 51.1 degrees (SD, 4.4 degrees). The in vitro ROM decreased to 19.8 degrees (SD, 7.3 degrees) in the facetectomized group of this study, which were allowed to heal for 6 months before death. Similar results were obtained in axial rotation and lateral bending. The findings show that after 6 months of healing, the injured canine spine, although acutely hypermobile, exhibited biomechanical characteristics that were not different from those of the normal intact specimens. PMID- 2263972 TI - Gunshot wounds to the cervical spine. AB - A retrospective review was performed on 28 patients with low-velocity gunshot wounds to the cervical spine. These composed 31% of all spinal gunshot wounds seen during the study period between 1979 and 1988. Surgical decompression did not seem to improve neurologic recovery in either the incomplete or complete patients. Neurologic recovery also appeared to be unaffected by the presence of retained intracanal bullet fragments. The authors found no advantage to routine neck exploration of this penetrating injury. Complications were seen in 93% of the patients. Most complications were thromboembolic, pulmonary, and urinary tract infections. No cases of instability occurred as a direct result of the gunshot wound. No deaths occurred in this series. Two cases of posttraumatic syrinxes were diagnosed. The authors' current treatment recommendations for these patients include selective wound management and observation of retained intracanal bullet fragments in patients with complete lesions. Surgical decompression after this injury is not recommended. PMID- 2263971 TI - Prognosticating study for cervical myelopathy using evoked spinal cord potentials. AB - One hundred twenty-three cases of cervical spondylotic and ossification of the posterior longitudinal ligament (OPLL) myelopathy cases with long tract signs subjected to surgical treatment were studied to identify the most important factors having an influence on postoperative outcome using evoked spinal cord potentials (ESCP). Disappearance and positive wave changes of these potentials at the level of responsible lesions and slow conduction velocity under 40 m indicated an unsatisfactory outcome. Localized-lesion cases diagnosed by ESCPs had excellent results, significantly more so than extensive-lesion cases, regardless of operative methods. In 123 cases, 76% were found to have localized lesions, while the other 24% showed extensive lesions. Concerning the difference between CSM and OPLL, 54% of OPLL and only 14% of CSM demonstrated extensive lesions. PMID- 2263973 TI - Evaluation of current extrication orthoses in immobilization of the unstable cervical spine. AB - An experiment was designed to evaluate the comparative stabilizing efficacy of several widely used semi-rigid orthoses applied to unstable fresh cadaver cervical spines subject to load. Cadaver specimens were surgically destabilized at the C4-5 segment. Lateral radiographs of the destabilized spine were obtained before and after collar placement and after the application of a 5-pound flexion force. Data analysis employing a one-way analysis of variance showed no statistically significant difference in the Necloc's, Philadelphia Collar's, or the Stifneck's ability to stabilize the cervical spine against a deforming flexion force (P greater than 0.05). They all provide translational stability while allowing angular changes to occur with application of the flexion force. The Philadelphia Collar Halo System is statistically superior to all three of the aforementioned collars in prevention of both translation and sagittal rotation (P less than 0.05). PMID- 2263974 TI - Immediate closed reduction of cervical spine dislocations using traction. AB - Cervical facet dislocations may be reduced rapidly and effectively using axial traction with weights applied at over the traditional 45-pound limit. Fifty-three sequential patients with cervical facet dislocations were reviewed. Thirty-nine patients required more than 50 pounds of traction to achieve rapid reduction. Sixty-eight percent of the entire series showed significant improvement in neurologic function. There were no cases of significant loss of function. A cadaver study confirmed that the cranial tongs could support over 100 pounds of traction. Careful application of up to 100 pounds seems to be associated with a low risk of neurologic compromise or tong failure, but results in effective reduction of dislocations. PMID- 2263975 TI - Compressive strength of autologous and allogenous bone grafts for thoracolumbar and cervical spine fusion. AB - The selection of the bone graft type for stabilization of spinal fusion depends on availability, the clinical situation, and the desired mechanical stability. The authors determined the potential immediate postoperative compressive strength of various types of bone grafts under axial compression on a material testing machine. The fibular strut graft (5,070 +/- 3,250 N, mean +/- standard deviation [SD]) was significantly stronger (P less than 0.05) than the anterior (1,150 +/- 487 N) and posterior (667 +/- 311 N) iliac crest grafts, and the rib grafts (452 +/- 192 N). Hydroxyapatite grafts with a pore size of 200 mu were significantly stronger (P less than 0.05) than those with a pore size of 500 mu (1,420 +/- 480 N versus 338 +/- 78 N). Ethylenoxide sterilization had no significant effect on the immediate compressive strength. Bicortical and tricortical Bailey-Badgley and Cloward bone grafts also were compared. Results showed that all cervical graft types may be sufficiently strong to support sizable loads. PMID- 2263976 TI - Anterior cervical plate fixation with the titanium hollow screw plate system. A preliminary report. AB - Morscher, of Switzerland, has developed an anterior cervical spine plate system (THSP) that does not require screw purchase of the posterior cortex. This design eliminates potential neurologic complications usually associated with the anterior plate system, but maintains the mechanical advantages of internal fixation. The authors reviewed 13 consecutive patients in whom the THSP system was applied. Indications for the use of this device included acute trauma in three patients, trauma of more than 6 weeks' duration in five patients, and spondylosis in five patients. Fifteen plates and 58 screws were placed, with no screws purchasing the posterior cortex. Postoperative immobilization varied from no immobilization to four-poster brace. With a mean follow-up of 13 months, all 13 patients went on to fusion. One patient had screws placed in the disc rather than in bone and went on to malunion. In all other patients, radiographs did not demonstrate screw migration, screw-bone lucency, graft dislodgement, or malunion. No patient suffered neurologic injury as a result of this device. The THSP system facilitates reliable fusion with minimal complications. Its use should be considered in multilevel anterior spine defects, posttraumatic cervical kyphosis, and cervical fractures with posterior disruption requiring anterior fusion. PMID- 2263977 TI - Ligamentous laxity across C0-C1-C2 complex. Axial torque-rotation characteristics until failure. AB - The axial torque until failure of the ligamentous occipito-atlanto-axial complex (C0-C1-C2) subjected to axial angular rotation (theta) was characterized using a biaxial MTS system. A special fixture and gearbox that permitted right axial rotation of the specimen until failure without imposing any additional constraints were designed to obtain the data. The average values for the axial rotation and torque at the point of maximum resistance were, respectively, 68.1 degrees and 13.6 N-m. The specimens offered minimal resistance (approximately 0.5 N-m), up to an average axial rotation of 21 degrees across the complex. The torque-angular rotation (T-theta) curve can be divided into four regions: regions of least and steadily increasing resistances, a transition zone that connects these two regions, and the increasing resistance region to the point of maximum resistance. The regions of least and steadily increasing resistances may be represented by two straight lines with average slopes of 0.028 and 0.383 N m/degree, respectively. Post-test dissection of the specimens disclosed the following. The point of maximum resistance corresponded roughly to the value of axial rotation at which complete bilateral rotary dislocation of the C1-C2 facets occurred. The types of injuries observed were related to the magnitude of axial rotation imposed on a specimen during testing. Soft-tissue injuries alone (like stretch/rupture of the capsular ligaments, subluxation of the C1-C2 facets, etc.) were confined to specimens rotated up to or close to the point of maximum resistance. The specimens that were subjected to rotations up to the point of maximum resistance of the curve spontaneously reduced completely on removal from the testing apparatus. Spontaneous reduction was not possible for specimens tested slightly beyond their points of maximum resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2263978 TI - [The new public health: advances in research]. PMID- 2263979 TI - [Relationship between reproductive patterns and infant mortality: alternative interpretations]. AB - A secondary analysis of the data of the Mexican National Fertility and Health Survey of 1987 (ENFES for its spanish acronym) was undertaken in order to study the relationship between reproductive patterns and child mortality. A total of 13,216 births and 711 infant deaths occurred 1 to 15 years previous to the survey were studied. The main conclusions are: 1) it is the adverse social, economic and environmental conditions surrounding young mothers (15 to 19 years) which are responsible for the excess mortality found in their children; 2) children of older women (35 and more years) experience increased mortality only in the late fetal period, this suggesting that a biological mechanism is mainly at stake; 3) the relative risks of death of first births, as compared to subsequent ones are generally smaller than one, indicating that first births have a lower probability of dying. The relative risk of death of first born relative to subsequent births, on the other hand, decreases with increasing age at death, suggesting that biological factors such as low birthweight and intrapartum complications are possibly important as well; 4) relative risks of death for short-spaced as compared to well spaced births were found, in general, to decrease from the late fetal to the neonatal and to the postneonatal periods. This points to a biological pathway, possibly via maternal nutrition, for the effect of spacing on child mortality. PMID- 2263980 TI - [Mortality as a result of accidental and intentional injuries in the Federal District from 1970 to 1986]. AB - This article presents the results of a retrospective analysis of unintentional and intentional injury mortality in Mexico City for the period 1970-1986. The mortality rates and trends were obtained out of 73,197 registered deaths, (according to the 9th revision of the International Disease Classification). Deaths due to the earthquakes of 1985 were not included. The trend of mortality is undefined (r = -0.430). The most important causes of death were: traffic accidents, homicides, and others accidents. Males accounted 77 per cent of the deaths. The most affected age groups were 15-19 and 20-24 years. The potential years of life lost were analyzed. This study provides information for the prevention and control of injuries and for future research in this field. PMID- 2263982 TI - [Utilization of prenatal care services: influence of perceived morbidity and of social networks of support]. AB - Differences in prenatal help seeking patterns were found in a sample of women of a household survey (9,139) that showed a high prenatal care coverage. The personal factors associated with the help seeking behavior were: the nature and individual perception of the symptoms and the existence of social support networks. Symptoms that make woman suspect of risk, produced a high demand of medical consultation (between 75 and 100%). Bothersome symptoms produced a medium utilization associated with its prevalence. Emotional symptoms produced a low demand of medical consultation (between 18 and 27%). Pregnant women who obtained support from their social networks consulted the doctor 3.3 times as much as those who didn't have a social network. The reinforcement of women's interaction with their natural social network is recommended as one of the basic components of prenatal care. PMID- 2263981 TI - [Trends in mortality from ischemic cardiopathy in Mexico, from 1950 to 1985]. AB - This paper presents the results of an ecologic study of the trends of ischemic heart diseases (IHD) (ICD 9th 410-414) from 1950 to 1985 in Mexico. The mortality rates area strongly related with age and sex. Among those aged 30 to 59 years old, the male-female ratio (MFR) was 2.5 whereas in those aged 60 or more the ratio was 1.2. The mortality rates for IHD increase over time, particularly when converted in logarithms (r = 0.89). There were important differences in the regional mortality patterns by age and gender. Among males the northern region showed a mortality risk 2.5 times higher than the southern region; this risk increases (3.0) in those older than 60 years old. The increasing risk modifiable risk factors such as smoking, cholesterol and hypertension. PMID- 2263983 TI - [Potential coverage and real coverage of ambulatory health care services in the state of Mexico. The case of 3 marginal communities in Atenco and Chalco]. AB - Less than a third of the non-insured population studied through a sample in the State of Mexico was covered by the Institute of Health of the State of Mexico. This low coverage was observed in spite the fact that health services were available within 2 kilometer radius. 33 per cent of the non-insured preferred to utilize other services within their own community, and 24 per cent of them traveled to bigger localities to receive care. These results suggest that to attain adequate coverage, utilization patterns should be investigated so that health services can meet the needs of the target population. PMID- 2263984 TI - [Policies for training and employment of physicians in Mexico 1917-1988]. AB - In this article we analyze education and employment policies for medical doctors in Mexico, which have led to a situation characterized by unemployment, under employment and multiple-employment in urban areas, as well as lack of services in several rural zones. The analysis is divided into four defined periods according to the modes of State participation in health care: 1917-1958 (creation and slow growth of health care institutions); 1959-1967 (growth of scientific medicine); 1968-1979 (crisis period); and 1980-1988 (reform). In each one of these periods the evolution of medical manpower is analysed through the actions of three main actors: the State, the universities and the medical profession. The general conclusion of this historical analysis is that the present imbalance in the medical labor market has derived from a lack of joint planning of supply and demand, where by the educational and health care institutions, could decide together the crucial aspects of the quantity and quality of doctors that the population requires. PMID- 2263985 TI - [Equity in charges for hospital medical services: the case of recovery charges in the Health Department]. AB - In this paper the authors stated the performance of the National System of Charges for Medical Services of the Mexican Ministry of Health. The study focus the analysis on 1,776 charges on hospitals at a secondary level of attention. It includes a presentation of the background of the System, and it's regulations, major problems and irregularities. The main founding were: a) irregularities on the classification for payment of the patients according to social class. The 67 per cent of users were classified in the upper class section; b) additional charges of 109 per cent on deconcentrated states; c) fees don't established on information on costs. The authors recommended: 1) Establishment of cost units on regional basis; 2) standarization of procedures of socioeconomic classification, exemption o payment and disminution of discretional procedures; 3) programmed adjustment on fees; 4) Monitoring of the system; 5) integration to the System of the third level of attention and the descentralized states and; 6) solution to budget problems. PMID- 2263986 TI - [Limitations of infant mortality as a health indicator]. AB - Infant mortality is usually accepted as a sensitive indicator of living conditions, and of the coverage and quality of health care in a specific country. However, the validity of this indicator in middle-income countries presents some important limitations. First, underegistration of infant deaths is a common feature. In second place, the national figures hide the great inequalities that may exist among different social sectors and regions. In this paper, the limitations of Mexico's infant mortality rate are analyzed. Underegistration is demonstrated by comparing infant mortality rates obtained from vital statistics data and national health surveys. Differences among social sectors are evident when specific infant mortality rates are compared. Inequalities have been increasing in the last years. PMID- 2263987 TI - [A database for research in public health]. AB - Epidemiological and health system research projects are often delayed due to the difficulties to build validated data basis in personal computers. This papers presents a new computer interactive program for handling numeric data from a given questionnaire to a structured archive. The questionnaire includes the basic variables of the dwelling and of the members of the household. A list of sociodemographic and health variables are selected, although other variables can be easily added, according to special needs. All the intermediate steps regularly needed to construct a data base are included in the package: capture, verification, validation and record linkage. The package is equipped with the basic procedures needed to produce tabulations and basic statistical analysis. PMID- 2263988 TI - [Strategies for applied research]. AB - The need of increasing the amount and quality of applied research in the health field es emphasized. The social and economical determinants of health and health care services require a multidisciplinary approach. The most important issue is the utilization of research results in the definition of policies and in the decision making process. Some of the barriers and obstacles to implement research results are discussed as well as the strategies that can be put forward to overcome the former. It is suggested tah participatory research could be an innovative methodology to improve the application of research results. Participative research is a collaborative effort that involves different actors of the health arena including administrators, health personnel, community members, and the researchers themselves. This type of research carries out diagnostic and intervention activities from the very beginning of the studies; its main strength is that decision made and the community members are active participants, impinging a scientific approach to their daily work and so the application of results is facilitated through out the process. PMID- 2263989 TI - [Scientific research and health problems. 1934]. PMID- 2263990 TI - [Multiple meningiomas--diagnostic and therapeutic problems]. AB - The authors present the case of a 0-year-old patient with multiple meninglomatous intracranial foci. They draw attention to the relatively rare occurrence of this condition and its complexity from the diagnostic and therapeutic aspect. The incidence of multiple meningiomas is more typical for advanced age (above 60 years), whereby their size increases with age and the male:female ratio is 1:3. PMID- 2263991 TI - [Analysis of the causes of failure in the treatment of simple traumatic epidural hematomas]. AB - In the course of 5 years (1983-1987) in the North Bohemian region 88 patients were operated on account of epidural haematoma (EDH). The majority of patients (71%) were treated in a regional hospital. Computed tomography made it possible to divide the group into associated and simple EDH. In the submitted paper the authors discuss only simple EDH, as associated injuries modify the clinical picture. Of 34 simple EDH 85.3% had an atypical course. Alcohol, different localizations of the haematoma or concurrent polytraumatism were the most frequent cause of an atypical course and thus a late diagnosis. These are in the authors' opinion the most frequent causes of failure. Supporting factors were shortcomings in the organization and restricted transport facilities. The finding of an ipsilateral cranial fracture was more typical for the diagnosis of EDH than the presence of the classical triad. The mortality in simple EDH was 26.5% and the morbidity also 26.5%. Only those patients died who were operated in areactive motor unconsciousness--i.e. late. PMID- 2263992 TI - [The present status of thoracic surgery in Slovakia]. AB - The authors submit a report on the state of thoracic surgery in the Slovak Republic, based on the number and structure of thoracic surgical operations made in 1983-1987. Twenty departments were concerned with thoracic surgery and 21 surgeons had the qualification of thoracic surgeons. The authors mention only briefly problems pertaining to the organization of the discipline. PMID- 2263993 TI - [Traumatic chylothorax and chyloperitoneum]. AB - Traumatic chylothorax and chyloperitoneum are rare. Effusion of the chyle into the pleural cavity occurs after severe injuries of the chest wall after pretentious surgical operation in the posterior mediastinum and after operations of the cardiovascular system. The authors recorded one observation after operation of a patent ductus arteriosus and controlled the situation by a conservative procedure. A traumatic chyloperitoneum develops typically after a minor or obscure injury. The pathological picture usually develops slowly, in rare instances it imitates an acute abdomen. The condition calls for laparotomy. Only in rare instances a fissure is detected in the posterior peritoneum and it is very difficult to detect the sites of injuries of lymphatic vessels. The authors treated three patients. All were operated, two were subjected to laparotomy twice. A relapsing chyloperitoneum was brought under control by hitherto non published surgical procedures: in one instance by communication of the abdomen with the posterior mediastinum, in the second case by ligature of the lymphatic vessels close to the vasa mesenterica cran. All patients recovered. PMID- 2263994 TI - [Findings in the abdominal cavity after ultrasonically controlled punctures]. AB - The authors describe three cases where laparotomy was performed within short time intervals after puncture under ultrasonic control. In none of the patients substantial changes were detected in the abdominal cavity in conjunction with the punctures. PMID- 2263995 TI - [Diffuse peritonitis and its late sequelae]. AB - The author gives an account of the late complications in patients operated at the surgical department of the District Institute of National Health Michalovce on account of diffuse peritonitis in 1966-1975. A total of 258 patients were examined who attended from a total number of 505 invited, operated during the ten year period under investigation. The high incidence of chronic sequelae and their serious character must be the reason for seeking steadily reserves in surgical treatment of diffuse peritonitis as well as during postoperative care. PMID- 2263997 TI - [Modified traction cerclage in fractures of the outer ankle]. AB - The authors describe two techniques of osteosynthesis which can be used as the method of choice in suitable types of fractures. Both were elaborated as the author's modification in 1978 and used in the course of 10 years in 24 instances. They can be applied without special instrumental equipment in any department. The authors consider them very stable without requiring additional plaster immobilization and the authors use early rehabilitation immediately after operation. The authors never observed usuration of the bone beneath the cerclage or slower healing, pseudoarthrosis or any other complications. They assume that the described methods may supplement the therapeutic range and be sometimes a good starting poit from a situation which would be otherwise, difficult to resolve. PMID- 2263996 TI - [Cefuroxime axetil (Zinnat)--laboratory and clinical study]. AB - The authors investigated the antibacterial action of cefuroxim in vitro and proved its relatively broad spectrum of action. Administration of the esterified form, Zinnat, produced very satisfactory therapeutic concentrations of cefuroxim in serum, bile tissue of operated gallbladders. The prophylactic administration of the combined parenteral and oral form of cefuroxim proved excellent in biliary surgery in twenty patients. PMID- 2263998 TI - [Spastic complications in free flap transfers]. AB - The authors follow up spastic reactions in free flap transplantations. In experiments on rats groin flaps were transplanted and during their preparation models of four types of spasms were made--segmental spasms of the afferent artery of the flap, spasms of the whole artery, spasms in the flap and tissue shock of the flap. The authors discuss possibilities of influencing and preventing spasms under experimental conditions and in clinical practice. PMID- 2263999 TI - [Preoperative diagnosis of cholangiolithiasis]. AB - The authors analyzed the sensitivity of preoperative diagnosis of Bile Duct Stones in 360 operated patients with Bile Duct Stones. They evaluated intravenous cholangiography, sonography, percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) with the possibility of endoscopic operations. The authors recommend after evaluation of anamnestic data, physical examination and results of biochemical examination always to make a sonographic examination (sensitivity for Bile Duct Stones 60%), to use in some indicated cases ERCP with the possibility of endoscopic operations (sensitivity 91%) and finally peroperative examinations in operated patients. Intravenous cholangiography (sensitivity for Bile Duct Stones 41%) and PTC (sensitivity 93%) should be reserved for those patients where for technical reasons sonography and ERCP cannot be used. PMID- 2264002 TI - Testing for HIV infection in STD clinics: how aggressive should we be? PMID- 2264001 TI - [Rectoanal perfusion manometry--methods and results in healthy persons]. AB - The authors elaborated a method of rectoanal perfusion manometry as part of the objective examination of the functional state of continence structures. They describe in detail the examination method and manometric equipment. In a group of 10 volunteers, 8 incontinent patients and 23 subjects after operations causing improved continence they draw attention to the great sensitivity and specificity of the examination as well as to the correlation of manometric results with results of Holschneider's evaluation by a point system. This method should be used in departments concerned with rectoanal surgery. PMID- 2264000 TI - [Late results of ileorectal anastomosis in proctocolitis]. AB - In 1961-1986 at the Surgical Clinic of the Institute for Postgraduate Medicine in Prague 49 colectomies were performed with ileorectal anastomosis. The operations were usually made in several stages. The remote results were evaluated after an interval of 10 to 26 years in 33 patients and were good to satisfactory in 82%. Malignant degeneration in the rectum was not observed. The relatively favourable results can be ascribed to careful selection of patients and frequently also the multi-stage procedure. Ileorectal anastomoses are still justified in the surgical treatment of proctocolitis. PMID- 2264003 TI - Behavioral relapse among homosexually active men: implications for STD control. PMID- 2264004 TI - The syphilis epidemic in Connecticut: relationship to drug use and prostitution. AB - Syphilis rates in Connecticut increased four-fold between 1986 and 1988. During this time there were also signs of a large increase in cocaine use in the state. We studied links between these parallel trends in drug use and syphilis by examining two sources of data: information collected during syphilis case interviews and information from the syphilis screening program at the state's prison for women. As syphilis rates rose, there were large increases in the percentage of women with syphilis who reported prostitution or illicit drug use. In 1988, 41% of women with syphilis reported cocaine use, and 19% reported prostitution; 21% of male heterosexuals with syphilis reported cocaine use, and 31% reported sexual contact with prostitutes. Among incarcerated women, syphilis infection was frequent: of 113 women incarcerated for possession of illicit drugs in 1987-88, 7% were found to be infected with Treponema pallidum, and of 187 women incarcerated for prostitution in these years, 14% were infected. In both groups of incarcerated women studied, cocaine users had the highest syphilis rates, and those who administered drugs nonintravenously had rates similar to those who administered drugs intravenously. We concluded that the syphilis epidemic in Connecticut is related to the increase in use of illicit drugs (primarily cocaine) and that female drug users are at very high risk of syphilis regardless of whether they administer drugs intravenously or nonintravenously. We recommend that syphilis control efforts focus on wider serologic screening and early treatment of drug users, prostitutes, and their sex partners. PMID- 2264005 TI - Voluntary human immunodeficiency virus testing, recidivism, partner notification, and sero-prevalence in a sexually transmitted disease clinic: a need for mandatory testing. AB - Universal, voluntary testing for antibodies to the human immunodeficiency virus (HIV) was offered to 17,092 eligible clients attending a public sexually transmitted disease clinic between March, 1988 and June, 1989. In an environment of legally mandated reporting and partner notification, 15,649 (91.6%) clients were tested, 160 of whom were HIV sero-positive. Client acceptance of testing is discussed, and the serologic data compared with results of a federally funded sero-prevalence survey conducted in-clinic. A recidivism rate of 20% was observed among sero-positive individuals. Of 159 contacts for whom HIV sero-status was determined, 66 (42%) were seropositive. It is proposed that, in the setting of sexually transmitted disease clinics, HIV testing be changed from a voluntary service to a mandatory test. Some benefits of this change are defined. PMID- 2264006 TI - Treatment of uncomplicated gonococcal urethritis with single-dose ceftizoxime. AB - In areas such as Los Angeles, California, where penicillin-resistant Neisseria gonorrhoeae accounts for 1% or more of all gonorrhea strains isolated, third generation cephalosporin agents have replaced penicillin as standard therapy. Ceftriaxone, the agent recommended by CDC guidelines, or ceftizoxime, an alternative agent have excellent activity against all strains of N. gonorrhoeae. One hundred seventy-five male patients with clinically and microbiologically confirmed gonococcal urethritis were treated with single-dose ceftizoxime 250 mg IM (50 patients) or 500 mg IM (125 patients). Cure was demonstrated clinically by repeat cultures of urethral discharge in all patients, including those with infections from penicillinase-producing strains of bacteria. None of the patients experienced complications or allergic reactions to ceftizoxime. Given the lower unit-of-use cost of ceftizoxime, its routine in place of ceftriaxone could result in substantial cost savings in those institutions that treat large numbers of patients with uncomplicated gonococcal urethritis. PMID- 2264007 TI - HIV antibody in persons screened for syphilis: prevalence in a New York City emergency room and primary care clinics. AB - An anonymous human immunodeficiency virus (HIV) seroprevalence survey was performed on bloods sent for syphilis serologic testing from the general medical or pediatric clinics or emergency room of a municipal hospital in the Bronx, New York City. From July-December 1987, 549 sera from persons aged 15-54 were collected. HIV antibody was detected in 29/549 (5.3%) sera, increased with age from 0% in the group under 20 to 16.7% in those aged 35-39, and was significantly higher in men (27/230, 11.7%) compared to women (2/319, 0.6%) (P less than .05). Among men aged 35-39, 10/29 (34.5%) were HIV infected. The HIV seroprevalence in emergency room sera was 8/61 (13.1%) versus 21/488 (4.3%) from the out-patient clinics (P less than .05). The presence of a reactive syphilis serology was strongly associated with HIV infection independent of gender (Mantel-Haenszel summary odds ratio (OR) 4.1, 95% CI [1.8, 7.7]) but was stronger for women with reactive syphilis serologies (OR 45.5, 95% CI 5.3, 387.6) than for men (OR 2.6, 95% CI 1.2, 5.8). AIDS prevention strategies may reach at-risk sexually active individuals by focusing on hospital-based emergency rooms and out-patients clinics in areas with high HIV seroprevalence. PMID- 2264008 TI - Routine voluntary HIV screening in STD clinic clients: characterization of infected clients. AB - Since January 25, 1988, the Baltimore City Health Department has offered routine, confidential, human immunodeficiency virus (HIV) testing to clients of the city's two sexually transmitted disease (STD) clinics. During the first 11 months of the program, testing was offered at 20,843 patient visits and was accepted at 15,181 (73%) of these; 612 (4%) individual clients had results that were positive for HIV. Four hundred thirty-seven (71%) seropositive clients returned for test results, post-test counseling, and further evaluation. Most HIV-infected clients were single, and black men accounted for 75% of seropositive individuals. HIV infected women tended to be younger than infected men (7% of the female clients were adolescents). Although homosexual activity, intravenous drug use, and sex with a partner at risk were common risk factors for seropositive clients, after two interviews 17% of men and 38% of infected women did not report traditional risk factors for HIV infection. Most clients were asymptomatic or had generalized lymphadenopathy at the time of HIV diagnosis. Health care resources for these individuals were limited; 62% of men and 85% of women either had no health insurance or received public assistance. Routine, voluntary, confidential HIV counseling and testing is a practical, effective means to identify HIV-infected individuals among clients being treated at STD clinics. Identification of these individuals early in the course of infection provides opportunities to implement early follow-up and therapy, to counsel clients to help prevent further spread of infection, and to obtain useful information for projecting future health care needs and policy. PMID- 2264009 TI - Report of the NIAID Study Group on Integrated Behavioral Research for Prevention and Control of Sexually Transmitted Diseases. Part I: Issues in defining behavioral risk factors and their distribution. PMID- 2264010 TI - The NIAID Study Group on Integrated Behavioral Research for Prevention and Control of Sexually Transmitted Diseases. Part II: Issues in designing behavioral interventions. PMID- 2264012 TI - Earnings replacement rates of new retired workers. PMID- 2264011 TI - The NIAID Study Group on Integrated Behavioral Research for Prevention and Control of Sexually Transmitted Diseases. Part III: Issues in evaluating behavioral interventions. PMID- 2264013 TI - Studies on posterior composite resins with special reference to class II restorations. AB - Longevity, clinical performance and some related factors of posterior composite resin restorations were investigated through clinical follow-up and laboratory studies in vivo and in vitro. Class I and Class II restorations using two experimental posterior composite resin materials were followed clinically for a four-year period. USPHS evaluation criteria were used. Assessments of wear were also made indirectly using the Leinfelder method. Marginal leakage of bacteria (in vivo) and of dye (in vitro) were studied on modified loaded Class II composite resin restorations lined with GlumaR and LifeR. The grade of conversion (cure) of the posterior composite resin material and the colonization of bacteria at proximal tooth surfaces restored with posterior composite resins were evaluated. Seven per cent of the restorations were evaluated as failures and had to be replaced during a 4-year period. The failures were mainly due to fractures and postoperative sensitivity. The calculated occlusal wear rate was 34-40 microns/year. Occlusal loading of Class II restorations in vitro resulted in a higher frequency of restorations with marginal leakage. The marginal leakage for occlusally-loaded Class II restorations in vivo and in vitro could be reduced if dentine bonding was utilized. The grade of conversion (cure) was increased in the in vivo situation compared to the in vitro. Bacterial colonization of strepococcus mutans on the proximal surfaces of posterior composite restorations showed higher frequencies compared to that on sound tooth surfaces. From the results of these studies, it may be concluded that the tested posterior composite resin materials can be used in Class I and II restorations with a good prognosis for at least 4 years. When posterior composite resins are used as restorative for posterior teeth, the following conditions should be considered: The occlusal loading should be minimal, dentin bonding should be used, the increased risk of colonization of streptococcus mutans should be acted on and regular clinical and radiographical follow-up should be performed. PMID- 2264015 TI - The effect of an airbrasive instrument on soft and hard tissues around osseointegrated implants. A case report. AB - A 40-year-old woman with natural teeth in the upper jaw and a complete lower denture was treated with six osseointegrated implants connected to a fixed bridge. On a recall visit 6 months posttreatment an air powder abrasive devise Prophy-Jet had been used to remove calculus and debris from the titanium abutments by the referring dentist. This resulted in an acute clinical reaction characterized by pain and submucosal emphysema. Furthermore, radiographs revealed break down of the marginal bone surrounding the fixtures. The treatment and follow-up period became long. These observations suggest that the use of air powder abrasive instruments is not the treatment of choice in the maintenance care of osseointegrated titanium implants. PMID- 2264014 TI - Diskectomy in treatment of disk derangement. A one and three year follow-up. AB - Diskectomy for treatment of temporomandibular joint disk derangements was evaluated clinically. The study comprised 40 consecutive patients (50 joints) with pain in the joint area and functional impairment not alleviated with nonsurgical therapy for at least 6 months. Diskectomy was performed in 32 joints. In 18 joints both diskectomy and minor arthroplasty were performed. No disk substituting implants were used. At 1 year follow-up 85% of the patients were free of symptoms from the temporomandibular joint area and showed normalized mandibular movements. Twenty patients were followed for 3 years. Two patients with arthrosis showed recurrence of symptoms. It was concluded that diskectomy is an effective surgical procedure for treatment of temporomandibular joint disk derangements. PMID- 2264016 TI - Impression technique for RPDs. A comparison between two methods. AB - The purposes of this study were threefold, 1) to develop a method for comparing various impression techniques and materials, 2) to compare the extension of impressions with ZOE-paste and silicone, and 3) to evaluate the precision for each method. A special device was constructed in order to secure an identical position of the impression trays. The results indicated that ZOE-paste impression in a border moulded tray produced more extended impressions lingually but buccally there were no difference between the chosen materials/method. No differences in precision of the two methods could be measured. PMID- 2264017 TI - The time employed for care of permanent teeth in children and adolescents. AB - Data were compiled from the records of dental care given to 199 patients from 6 to 19 years of age. The restorative treatment of permanent teeth, including the time for examinations, radiographs and final polishing, accounted for 74% of the total time employed for dental care. It was especially noted that the youths with a caries prevalence of 25 or more filled surfaces at 19 years of age, constituting 24% of the patients, accounted for 65% of the number of filled proximal surfaces and 45% of all filled surfaces, while 38% of the time needed for restorative dentistry and 40% of the time used for individual prophylaxis was associated with this group. This study emphasizes the importance of early identification of the children at high risk for caries so as to provide appropriate preventive therapy. PMID- 2264018 TI - Bleeding time is prolonged during oral anticoagulant therapy. AB - We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor". PMID- 2264019 TI - Effect of recombinant human FVIIA on warfarin-induced bleeding in rats. AB - Recombinant human factor VIIa (rFVIIa) was given to warfarin-treated rats. One and two warfarin treatments reduced endogenous factor X levels to about 10% and less than 5%, respectively. The reduction of plasma levels of vitamin K-dependent coagulation factors was accompanied by a treatment-dependent prolongation of activated partial thromboplastin time (APTT) and prothrombin time (PT) as well as by increased bleeding time and blood loss in the rat tail bleeding test. rFVIIa 50 micrograms/kg and 250 micrograms/kg normalized PT and shortened APTT in rats given warfarin once. Bleeding was completely normalized by rFVIIa 250 micrograms/kg. In rats given warfarin twice rFVIIa 250 micrograms/kg shortened PT but had no effect on APTT, whereas the effect on bleeding was variable. The elimination half life of rFVIIa in rats was found to be 30-40 minutes. The study indicates that rFVIIa may be useful in patients with bleeding due to decreased levels of vitamin K-dependent coagulation factors. PMID- 2264020 TI - Production and characterization of monoclonal antibodies against rat platelet GPIIb/IIIa. AB - Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 98,000 (reduced), which were structurally analogous to human glycoprotein (GP) IIb/IIIa, i.e. rat GPIIb/IIIa. Two of four antibodies, named P9 and P55, strongly inhibited adenosine diphosphate (ADP)-induced aggregation of washed rat platelets and caused approximately 50% inhibition of human fibrinogen binding to ADP stimulated rat platelets, suggesting that rat GPIIb/IIIa serves as a fibrinogen receptor in ADP-induced aggregation. In contrast, two other antibodies, named P14 and P34, themselves caused aggregation of rat platelets in platelet-rich plasma (PRP) and the secretion of 14C-serotonin from 14C-serotonin-labeled PRP. These results indicate that rat GPIIb/IIIa plays an important role in platelet aggregation. PMID- 2264022 TI - Coagulation impact on chemotactic activity generation for polymorphonuclear leukocytes. AB - Chemotactic technique in agarose gel has exposed the attractive properties of human alpha thrombin with respect to human polymorphonuclear leukocytes. The observed chemotaxis is maximal between 1.4.10-5 M and 1.6.10-5 M but extends from 2.8.10-6 M to 2.2.10-5 M. Human prothrombin, in an identical concentration zone as that studied for thrombin shows no chemotactic activity on the polymorphonuclear leukocytes. During coagulation the formed alpha thrombin attracts the polymorphonuclear leukocytes to it's formation site. PMID- 2264021 TI - Effect of a synthetic thrombin-inhibitor MD805 on the reaction between thrombin and plasma antithrombin-III. AB - MD805, a synthetic thrombin-inhibitor, effectively retarded the time-dependent inactivation of thrombin which was generated endogeneously or added exogeneously in human plasma. The kinetical study of the time-dependent inactivation indicated that the type of inhibition was competitive and the obtained Ki of MD805 for thrombin was 3 x 10(-8)M. MD805 also inhibited the formation of thrombin-ATIII complex. These results indicated that the active site of thrombin was involved in the reaction between thrombin and ATIII, and that MD805 competed with ATIII for thrombin in exactly the same manner as it competed with fibrinogen or synthetic peptide substrates. As a result, MD805 would serve as a protective agent for ATIII from being consumed, in addition to its potent thrombin-inhibitory activity without the aid of ATIII. By contrast, heparin accelerated the time-dependent inactivation rate of thrombin and the formation of thrombin-ATIII complex, which indicates that heparin accelerates the consumption of ATIII. PMID- 2264023 TI - The antiplatelet effect of daily low dose enteric-coated aspirin in man: a time course of onset and recovery. AB - We have studied the onset and recovery of inhibition of platelet function by low dose aspirin. Enteric-coated aspirin 50mg daily was administered to five human volunteers for five weeks and then 100mg daily was given for a further five weeks. We studied platelet aggregation and thromboxane formation in response to a range of stimuli: ADP, adrenaline, arachidonate and collagen, and also measured thromboxane formation after coagulation of whole blood (serum thromboxane). The onset of inhibition of platelet aggregation was progressive over several days for each of the four platelet stimuli, and was synchronous with the inhibition of thromboxane formation. Maximum inhibition occurred by day three for the weak stimuli ADP and adrenaline, by day five for the stronger stimuli arachidonate and collagen, but did not occur until day eight for serum thromboxane. Further inhibitory effects on both aggregation and thromboxane generation were observed after 100mg daily. Two weeks after the cessation of aspirin the responses to collagen and arachidonate and serum thromboxane had returned to normal. Platelet aggregation in response to the weaker stimuli, ADP and adrenaline, still showed detectable inhibition two weeks after cessation of aspirin, but had returned to normal by four weeks. These experiments provided no evidence for an effect of aspirin on platelets separate to its effect on cyclooxygenase. The onset and recovery of inhibition of platelet function by low dose aspirin was dependent on the strength of the stimulus studied. PMID- 2264024 TI - [Topographic and therapeutic aspects of displacement of the abomasum to the right in cattle]. AB - A comprehensive anatomical description of the various types of right abomasal displacement, is followed by a discussion of the therapeutical aspects. Particular attention is paid to surgical and additional medical treatment. PMID- 2264025 TI - [Immunotherapy of squamous cell carcinoma of the bovine eye and of equine sarcoid]. AB - Squamous cell carcinomas of the bovine eye and equine sarcoids are briefly reviewed. A single injection of BCG into the tumour results in permanent regression of the lesion in 37 per cent of the cattle, regression followed by recurrence of the tumour in 26 per cent and in progressive growth of the tumour in 37 per cent of the cases. Recurrence may be prevented by repeated injection into the lesion. From 50 to 60 per cent of the cows will remain free from tumours. Equine sarcoids show a complete regression in 70-80 per cent of the cases. Tumours on the limbs show a less satisfactory response (lower rates of success, more complications) than do tumours in other areas of the body. PMID- 2264026 TI - [Chronic disease of the two sesamoid bones of the lower foot of the horse]. AB - The aetiology and pathogenesis of navicular bone disease and sesamoidosis are discussed on the basis of findings reported in the literature and research. A marked similarity is found to be present between the clinical presentation, aetiology and pathogenesis of these two diseases. In addition, the intra and juxta-articular signs of degeneration as seen in these diseases are similar to those seen in various forms of arthrosis. Circulatory disturbances resulting from partial or complete arterial occlusion, caused by arteriosclerosis, are likely to play an important role in the cause of degeneration of various anatomical structures occurring in navicular bone disease and sesamoidosis. In contrast, it is unlikely that overloading is a major factor in the aetiology of navicular bone disease and sesamoidosis, although it may be of importance in its pathogenesis. For a full understanding of the cause of arteriosclerosis, far more fundamental research is required. PMID- 2264027 TI - [Spavin in horses]. AB - The pathogenesis of bone spavin and its implications for diagnosis and therapy are reviewed. The pathogenesis of spavin can be divided into three phases, which are characterised by fibrillation of cartilage, osteolysis and ankylosis respectively. It will depend on the degree of osteolysis whether diagnostic anaesthesia should be added to standard clinical and radiological examinations. Satisfactory results of treatment in the group of patients with severe osteolysis can only be obtained by arthrodesis of the distal tarsal joints. It is expected that biomechanical investigations will provide a better understanding of the mechanical factors involved in the pathogenesis of spavin. For the time being, the only method of prevention will have to consist in strict selection and high level rearing of the young horses. PMID- 2264028 TI - [Soft tissue lesions of the equine carpus: roentgenological and echographic studies]. AB - Common soft tissue disorders of the equine carpus are fluctuating or firm soft tissue swellings, wounds and draining tracts. Survey radiography may show the size, position and origin of the swellings and reveals soft tissue calcification, accumulation of air and radiopaque foreign material. Contrast radiography enables accurate visualization of the size, shape, position and origin of fluctuating soft tissue swellings, demonstrates abnormal intersynovial communication and allows precise demonstration of the extent of puncture wounds and draining tracts. Ultrasonography allows differentiation between a firm solid or thick walled cystic lesion, clearly reveals injuries to tendons, muscle and ligaments, reveals minor irregularities of the wall and the lumen of distended tendon sheaths and may demonstrate radiolucent foreign material more clearly than contrast radiography. PMID- 2264029 TI - [Morphology of the immature radius and metacarpus in horses and the relationship to bone infection and osteochondrosis]. AB - In chondro-osseous disease in the foal there are three main categories of lesions: (i) synovitis alone (type S), (ii) synovitis accompanied by osteomyelitis originating in the epiphysis of the juxta-articular bone (type E) and (iii) synovitis accompanied by osteomyelitis originating directly adjacent to the physis of the juxta-articular bone (type P). Observations made in studies of the immature radius and metacarpus provide an explanation for the apparent predisposition of some joints for this disease. Relevant clinical and therapeutical aspects are discussed. PMID- 2264030 TI - [Force plate measurements for a quantitative assessment of the equine gait]. AB - Forces occurring between the hoof and the ground during the stance phase (i.e. the ground reaction forces GRF) can be analysed using a force plate. The average of a number of five to stance time and body weight normalised GRF recordings (data) will provide 'representative' GRF patterns. These can be used for objective and quantitative evaluation of various forms of therapy in equine orthopaedics as well as for locomotion research during various forms of equestrian sports. PMID- 2264032 TI - [The Veterinary Service Board. Aujeszky's disease]. PMID- 2264031 TI - [Movement analysis in the horse with special attention for the problem of skin displacement]. AB - Kinematic gait analysis is a rapidly growing field of veterinary research promising to become even more important in coming years. All modern analytical techniques are based on the use of skin markers and are therefore prone to suffering from a biological error caused by the sliding of the skin over the underlying skeletal structures. To investigate this error skin displacement was quantified at 18 relevant sites using techniques designed to ensure simultaneous visualization of skin and underlying bone. Mathematical models for correction of skin displacement were formulated. Application of these models to a kinematic analysis of the reciprocal apparatus showed that the marked discrepancy between in vivo and in vitro measurements previously reported was almost entirely due to the artifact caused by skin displacement. It is concluded that correction for skin displacement is of the utmost importance in basic biomechanical research, but is not required in clinical kinematic analysis in every case. PMID- 2264033 TI - [Prejudices against female veterinarians must be removed]. PMID- 2264034 TI - Heart-lung transplantation in 1990--indications, surgical technique, postoperative complications and outcome. AB - Using cyclosporine A (CyA), long-term results after heart-lung transplantation became possible. Since 1981, 761 clinical heart lung transplantations have been registered at the International Society for Heart Transplantation. Candidates for this operation reveal signs of irreversible heart and lung diseases which are caused by cardiac lesions (e.g. valvular disease, Eisenmenger reaction due to congenital malformation) or pulmonary disorders (e.g. primary pulmonary hypertension, emphysema, fibrosis). The standard surgical procedure necessitates three anastomoses which combine donor and recipient tracheae, right atria and aortae. Immunosuppression consists of CyA (blood levels of 300-500 ng/ml), azathioprine (1-2 mg/kg/d) and rabbit antithymocyte globuline (RATG) (IgG: 2-4 mg/kg/d). After the first 2 postoperative weeks, RATG is replaced by low dose methylprednisolone (0.3-0.1 mg/kg/d). As an alternative, RATG may be omitted completely. Postoperatively, a variety of complications may evolve. Early problems (within the first month) comprise acute pulmonary rejection, bacterial pneumoniae, and multiorgan failure. Diagnosis of acute lung rejection proves difficult; it includes clinical signs, chest radiographic appearances and cytoimmunological monitoring of the peripheral blood. Transbronchial lung biopsies are for precise diagnosis of similar value to endomyocardial biopsies after heart transplantation. Late postoperative complications comprise viral, bacterial, fungal, and protozoal infections and chronic obliterative bronchiolitis. With increasing experience, the 30 day mortality fell to below 20% according to the International Society for Heart Transplantation. The one-year survival rate between 1986 und 1988 was reported to be 61%. The results of some individual groups are even better. PMID- 2264035 TI - Indications and selection criteria for cardiac transplantation. AB - Assessment of indications for cardiac transplantation is a complex process including first a comparison of expected survival of a patient with end-stage heart disease, mostly ischemic or dilative cardiomyopathy, allocated either to conventional medical or surgical therapy or to cardiac transplantation, second the expected increase in exercise tolerance and quality of life after transplantation. Furthermore the exclusion of contraindications is required: severe irreversible secondary organ damage (especially of kidneys and liver), malignant tumors and systemic malignancies, severe pulmonary hypertension, florid infections, unstable psychosocial conditions of the patient and his surrounding. Although a considerable number of clinical, electrocardiographic, echocardiographic and hemodynamic factors have been defined as indicating very poor prognosis, there exists no prognostic index combining all these factors into a precise prediction of survival of an individual patient with end-stage cardiac failure. Whereas high survival rates have been concordantly documented for the first years after transplantation, the long-term prognosis cannot be estimated as yet with equally sufficient certainty, due to increasing observation of vasculopathies and of progressive myocardial (mostly diastolic) dysfunction of transplanted hearts. These problems suggest to continue with very careful selection of candidates for transplantation. Even in the case of cardiac decompensation and poor prognostic factors, usually a single examination of the patient is not sufficient, but rather a thorough observation of the patient over a period of time including an evaluation of the rate of clinical and hemodynamic decline and of the response to medical therapy. PMID- 2264037 TI - Tricuspid valve endocarditis in the drug addict: a reconstructive approach ("vegetectomy"). AB - This report describes the case of a 24-year-old female heroin addict with large tricuspid valve vegetation, recurrent septic pulmonary emboli, and renal failure, due to immune-complex nephritis. The clinical course was initially complicated by acute hepatitis A. Because of recurrent emboli and persistent fever despite adequate antibiotic therapy she underwent excision of the vegetation ("vegetectomy") and tricuspid valvuloplasty. She was well at follow-up 12 months later with trivial tricuspid regurgitation shown by doppler-echocardiography. Kidney and liver function were normal. Right-heart endocarditis in drug addiction and therapeutic approaches are discussed. In selected cases "vegetectomy" and valvuloplasty offer a promising therapeutic alternative. PMID- 2264036 TI - Long-term follow-up after orthotopic heart transplantation. AB - While infection and acute rejection continue to be the most frequent cause of early postoperative mortality, chronic rejection including both coronary vasculopathy and unspecific myocardial allograft failure and side effects of immunosuppressive therapy determine late survival and quality of life. Some data are presented of a systematic program for long-term follow-up of cardiac transplant recipients with particular emphasis on coronary vasculopathy and modern concepts in rejection detection and control. Infections remain a notable source of morbidity and mortality. The importance of continued efforts to prevent infection even in the Cyclosporin era has to be emphasized. Tricuspid insufficiency is influenced by the mismatch of recipient and donor heart size. Intraoperative adaptation of the recipient pericardium to the size of the donor heart reduces the magnitude. Unspecific graft failure has been observed to occur at an incidence of 8% three years after transplantation. Three types of rejection can be distinguished after heart replacement, the hyperacute rejection as a rare complication precipitated by preformed recipient antibodies to donor antigens, the acute rejection as a major risk factor for survival in the postoperative first year, and, finally, the chronic rejection which is an important factor for long-term survival and quality of life. Considering the detection and classification of the acute rejection, a semiquantification is advantageous because of its therapeutic relevance. The chronic rejection is characterized by vascular abnormalities, interstitial changes, and myocardial alterations. Of these, the vascular component is the most important clinically. The incidence of this coronary vasculopathy, taking all forms visible angiographically, is about 30-40% of surviving patients three years after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264038 TI - Valve replacement for aortic regurgitation: earlier operation may reduce the rate of late complications related to the prostheses. AB - Predictability of prosthesis- and sudden heart-related complications was examined in 121 patients who were alive 30 days after valve replacement (1965-86) for aortic regurgitation. A variety of prosthetic valves, mainly mechanical, were used. The Cox regression model was used to identify independent risk factors and to estimate the predicted freedom of events relative to combinations of these risk factors. In the following, linearized event-rates (LER) are given as number of events per 100 patient years +/- standard error. No risk factors could be identified for endocarditis (LER: 0.3 +/- 0.2) or anticoagulant-related hemorrhage (LER: 1.7 +/- 0.6). Only factors underlying deranged preoperative patient and heart status and cardioplegic method, but not the type of prosthetic valve, had predictive influence on the other complications. Predicted 10-year event-freedoms for low- versus high-risk estimate were 98% versus 46% for thromboembolism (LER: 2.1 +/- 0.6), 87% versus 68% for all prosthesis-related complications (LER: 5.0 +/- 0.8), 100% versus 0% for sudden heart-related events (LER: 2.0 +/- 0.5; myocardial infarction and arrhythmia), and 72% versus 38% for combined prosthesis- and sudden heart-related morbidity and mortality (LER: 7.0 +/- 1.0). By deciding to operate early in the course of aortic regurgitation, the rate of these complications may be "actively" reduced, and longevity and life quality of the patients improved. PMID- 2264039 TI - Combined mitral and aortic valve replacement with Bjork-Shiley prostheses: long term survival and valve-related complications. AB - Between 1974 and 1985, combined aortic and mitral valve replacement (DVR) was performed in 209 patients using Bjork-Shiley tilting-disc prostheses. Early and late mortality were 9.5% and 10.5% respectively for the entire series. Factors significantly influencing early mortality were: Emergency DVR, preoperative NYHA Class IV, double valve, critical stenosis, and small aortic replacement prostheses. The effect of the latter was augmented by the suboptimal orientation of the implanted prostheses. The overall survival was 74 +/- 4.4% at 12 years; but was only 40 +/- 6.1% at 8 years in patients who were in NYHA class IV preoperatively. Intermittent disc occlusion (DO) and thrombotic disc occlusion (TO), presented as early, anticoagulant related haemorrhage (AH) and prosthetic valve endocarditis (ENDO) as sporadic, and thromboembolism (TE) and paravalvular leak (PVL) as continuous risk factors. Freedom from all known valve-related complications was 77 +/- 4.5% at 12 years (DO, TO, AH, ENDO, TE, PVL: 98%, 97%, 96%, 96%, 88% and 89% respectively). Lethal DO and TO occurred in mitral prostheses. Freedom from reoperation was 95% at 5 and 12 years. Patient-related valve failure rate in this series is comparable with the other series which used mechanical prostheses and is lower than those which used bioprostheses. PMID- 2264040 TI - Combined multiple valve procedures and myocardial revascularisation. AB - We report a series of 21 consecutive patients undergoing combined multiple valve procedures and myocardial revascularisation between 1978 and 1988. There were 11 females and 10 males with a mean age of 58.5 (+/- 5.7) years. All patients were in NYHA Class 2 or more and 12 patients (57%) had angina. The mean left ventricular segment score was 7.9 (+/- 3.3). Five patients had undergone previous cardiac surgery. In all patients the aetiology of the valvular dysfunction was rheumatic. The first patient in the series was operated on using ischaemic arrest. The remaining 20 operations were performed using cardioplegia (2 crystalloid, 18 blood). A mean of 1.63 grafts per patient were inserted. There were 20 aortic valve replacements, 1 aortic valvotomy, 13 mitral valve replacements, 7 open mitral valvotomies, 1 mitral valve repair, and 1 tricuspid valve replacement. 1 patient had 3 valves replaced. Five deaths occurred in the series; all were due to low cardiac output and occurred prior to discharge from hospital. Follow-up ranged from 7 to 111 months (mean = 46 +/- 33). Three patients developed mitral paravalvular leaks, two of which were successfully repaired at 2 months and 2 years postoperatively. The third was asymptomatic. There were no late deaths and all survivors improved to NYHA Class 1 and had no angina. Early death was associated with increased perfusion time (p less than 0.01), the need for postoperative inotropic support (p less than 0.01) and high blood loss. No preoperative predictors of early death were identified. Multiple valve procedures and myocardial revascularisation carry a significant early mortality but are justified by the satisfactory long-term outcome. PMID- 2264041 TI - Internal mammary artery anomalies. AB - The internal mammary arteries (IMA) are considered to be the superior conduit in coronary bypass grafting (CABG). Anomalies of an IMA can influence the surgical technique and results; their true incidence is not well known. The IMA's were visualised angiographically in 262 consecutive patients undergoing cardiac catheterisation prior to CABG. Satisfactory visualisation was possible of 459/524 IMA's studied (88%). A total of 118/459 (26%) surgically significant anomalies was observed in 79/262 patients (30%): common origin of another large artery in 48/459 (11%), large side branches in 41/459 (9%), tortuosity in 21/459 (5%), atypical course or origin in 5/459 (1%), atherosclerotic lesions in 2/459 (0.4%) and spasticity of an IMA in 1/459 (0.2%). Angiographic visualisation of the IMA's resulted in modification of surgical strategy in 11/262 patients (4%); meticulous preparation because of difficult or atypical IMA anatomy was necessary in 68/262 patients (26%). These results demonstrate that significant anomalies of the IMA which might--when unrecognized--jeopardize IMA-flow after CABG are relatively common; they might escape detection during IMA take-down but can be diagnosed by angiography during catheterisation. PMID- 2264042 TI - A new internal mammary artery retractor. AB - A new retractor for asymmetric opening of the chest is presented. The instrument is mainly used for dissection of the internal mammary artery, but other applications are possible such as resection of large mediastinal tumors, or pulmonary resections through median sternotomy. The device is comprised of a standard retractor combined with a tilting mechanism which lifts one side of the chest (following median sternotomy) while depressing the other side, resulting in an asymmetric opening of the thoracic cavity. The retractor has been used routinely since late 1987. As of April 1990 it has been employed in more than 3000 operations, and has appeared to be safe and efficient. PMID- 2264044 TI - Giant lymphoid hamartoma of mediastinum (Castleman's disease). AB - The giant lymphoid hamartoma is known as a rare, benign, large, solitary, encapsulated mass of lymphoid tissue. It frequently involves mediastinum or pulmonary hilum. It may also occur in other various locations. Few of the patients may have general symptoms. The disease has been divided into two variants according to microscopic structure. These are hyaline vascular type and plasma-cell type. The hyaline vascular type is benign but the plasma-cell type meets malignancy criteria, so that the plasma-cell type has been subject to discussion whether it is suited to chemotherapy or not. Our case was a 55-year old male with persistent cough. There was a mass having a size of 6 centimeters on left pulmonary hilum on chest radiograph. Left thoracotomy was performed and a hilar lymphoid mass removed. The biopsy finding was "hyaline vascular type giant lymphoid hamartoma". No other therapy was done. Patient is well six months after the operation. PMID- 2264043 TI - Omental pedicle flap used to treat a bronchopleural fistula after diaphragma- pericardio-pleuropneumonectomy. AB - In a 47-year-old male patient a bronchopleural fistula was apparent 22 days after extended right-sided diaphragma-pericardio-pleuro-pneumonectomy for pleuramesothelioma. The thoracic cavity was infected. Rethoracotomy was performed and the fistula was closed using an omental pedicle flap. The bronchial stump became tight and the cavity fluid became sterile. No abdominal complications were seen. The patient died 8 months later from malignant pericardial infiltration. The ability of greater omentum to revascularize ischemic tissue, to absorb fluid and to resist local infection is proved and used in several subspecialities of surgery. Nevertheless the use of the greater omentum in the management of bronchopleural fistula has been rarely published. The reported case shows that the closure of a large bronchopleural fistula is possible by using the attributes of the omental tissue. PMID- 2264045 TI - Development, prerequisites and specific scope of general thoracic surgery: analysis of requirements and capacity for the Federal Republic of Germany (West). The German Society for Thoracic and Cardiovascular Surgery. AB - In the 1970s and 1980s the measures for providing the inhabitants of the FRG with regionally distributed facilities in thoracic and cardiovascular surgery took almost only heart surgery into account. In the field of thoracic surgery, by contrast, several centers were closed or used for other purposes. This development was due to the decline in tuberculosis, but also partly to the lack of exact statistics concerning thoracic surgery. The result has been a considerable deficit in the provision of specialized care for the population and stagnation in research. A nationwide questionnaire in 1989 showed that in 78.4% of the surgery departments asked general thoracic surgery was undertaken only occasionally (less than 100 interventions a year); 42.8% of the operations were undertaken by non-specialized surgeons. Malignant diseases dominated the case load. Because of the lack of sufficient thoracic surgery departments with appropriate specialized knowledge, it must be assumed that many patients with cancer of the thoracic organs are receiving either no, inefficient, or too late a treatment of their disease. Reorganisation of general thoracic surgery is necessary in order to provide the population with adequate facilities in this field. The existing thoracic surgery centers should be enlarged and attached to the universities in order to ensure research and teaching. Specialized treatment of thoracic surgical diseases can be achieved by reorganizing general surgery departments in the regional hospitals which already undertake thoracic interventions and by establishing additional thoracic surgery departments under qualified leadership. PMID- 2264046 TI - [Fructosamine as a valuable criterion for the evaluation of diabetic animals and its photometric determination]. AB - The new photometrical kit fructosamine is tested for its use with canine, feline and equine blood. Normal values of fructosamine in nondiabetic animals as well as adequately and inadequately stabilized patients are given. The measurement of fructosamine is an excellent new tool for diagnosis and treatment of diabetes mellitus and should become an essential part of the control of the course of diabetes mellitus in animals. PMID- 2264047 TI - [The clinical case. Munsterland dog, 9 years old, anorexic]. PMID- 2264048 TI - [BSE, bovine spongiform encephalopathy]. AB - Bovine spongiform encephalopathy, first described in 1985, has led to serious economical problems in the United Kingdom within a few years. In this review, the clinical picture, pathological findings and the etiologic and epizootiologic history of the disease are summarized. The potential threat to the Continental cattle population and the potential risk to human health are critically discussed. The known methods of diagnosis of the disease are also described. PMID- 2264049 TI - [Uterine perforation following an experiment in the correction of a uterine torsion in the 5th month of pregnancy. Illustrated report]. AB - In this case report a perforation of the uterus in a German Black Pied cow after correction of the uterine torsion in the 5th month of gestation is described. Because of the hopeless prognosis, the cow was slaughtered. An additional finding was a metaplastic keratinization of the chorionic epithelium in the form of a plaque. The reason and pathogenic meaning of this metaplasia is not known. In the discussion, therapy of the uterine torsion in such an early state of gestation is critically considered. PMID- 2264050 TI - [The problems of the success of afterbirth removal in cattle. Expert veterinary opinion]. AB - If a severe uterine inflammation is diagnosed 15 days post partum in a cow with retained placenta by clinical examination, it has to be assumed that this inflammation was already manifest two days before (in the discussed case at the time of purchase). By an external examination of the animal this genital inflammation cannot be seen, if there is no vaginal discharge or dried uterine fluids at the tail and around the vulva. The inflammation is the consequence of the placental retention, even if there has been veterinary assistance (manual removal of the retained placenta, antibiotic treatment of the uterus) in time. After manual removal of the placenta, part of it is normally left in the tips of the uterine horns; they cannot be reached by the veterinarian's hand. Even by additional means - like application of oxytocin, lifting the abdomen of the cow with the aid of a plank or trying to invert the tip of the uterine horn - the fetal membranes cannot always be totally removed. The statement that the placenta has been totally removed, is correct only if the end of the chorionic membranes could be clearly identified. Each placental retention in cattle carries the risk of reduced fertility. If a cow is sold a few days post partum, this defect, which can reduce the animal's breeding value, may be unnoticed. PMID- 2264051 TI - [The diagnosis of Eperythrozoon suis infection]. AB - Eperythrozoon infection can be diagnosed clinically and hematologically only during acute attacks. In the febrile phase it is possible to detect the eperythrozoon organisms in the blood smear. The best method for staining is that by acridine-orange and examination by fluorescence microscopy. Serological identification (IHA, KBR, ELISA) is suitable for herd diagnosis only, because of the undulating level of the titre. In the individual case only positive results are regarded as significant. The best method to diagnose a latent infection of eperythrozoon suis is to splenectomize a suspected pig. The infection with eperythrozoon suis is a herd problem, therefore an examination should be made whenever there are pale pigs with fever, or a reduction of efficiency or an increased susceptibility to other infections. PMID- 2264052 TI - [Possible applications of the biotest air microbe collector RCS Vet in swine housing]. AB - A practical test of the Biotest centrifugal air sampler RCS Vet to assess the air quality for microbial levels in pig houses is presented. Estimating the number of microbial colony-forming units (staphylococcus) was only possible after modifying the sampler. Measurement of the total count of microbial-forming units was only possible under controlled conditions because of the high level of organisms in the pig house air. The use of selective media to measure microbial levels in air is described. PMID- 2264053 TI - [Antibiotic resistance of important bacteria from clinical and dissection material of the Institute for Poultry Diseases]. AB - 631 bacterial strains isolated during 1989 from many avian species were tested for their antibiotic sensitivity. The sensitivity ranged from 34.9 to 92.9%. PMID- 2264054 TI - [Provisions for returning rehabilitated wild bird patients to the wild state]. AB - For the receiving, care, and rehabilitation of normally free-living birds which are sick or capable of rehabilitation, the provisions of the Civil Code, the game law, the laws relating to nature protection and protection of endangered species have to be considered. In this paper the requirements of the veterinarian, the patients, and the "rehabilitator" are given as a simplified review. Generally, it can be concluded that the rehabilitation of avian patients does not necessarily constitute a contribution to the support of the free-living population and is therefore not unconditionally useful. A relaxation of the regulations governing the keeping of protected avian species may better promote the interests of the birds involved. PMID- 2264055 TI - [The treatment basis for anticoagulants in horses]. AB - The pharmacokinetics of racemic phenprocoumon were studied in 8 adult horses after the single intravenous and oral administration of 0.75 mg/kg. After i.v. administration the plasma concentration of phenprocoumon showed a biphasic decline in time. The pharmacokinetics were calculated on the two-compartment open model. The average plasma half-life (beta-phase) was 22 hours, the apparent volume of distribution was 0.61 l/kg, Cltot was 25.2 ml/kg/h (13.9-40.9 ml/kg/h). The systemic bioavailability of oral phenprocoumon was 97.6%, Tmax was found to be 4-12 hours. The effect of phenprocoumon on the coagulation system was determined by the activity of Factor X, the Quick's one stage prothrombin time and the PTT. Factor X showed the most marked effect. A reduction of the content of Factor X was seen over 7-9 days, it decreased to 11-33%. Quick's one stage prothrombin time was reduced over 4-8 days, the lowest values were 22-55%. The PTT showed only a small reaction on the single administration of 0.75 mg/kg phenprocoumon. Differences in the effect on the coagulation between the i.v. and the oral administration could not be observed. In comparison to warfarin, phenprocoumon showed a longer t0.5 (beta) and produced a markedly longer hypothrombogenic reaction. Therefore phenprocoumon appeared to be more suitable for a long term anticoagulation therapy in horses than the structurally related warfarin. PMID- 2264057 TI - [Atopic dermatitis in dogs: new diagnostic criteria]. AB - The diagnostic features of atopic dermatitis in man and dogs are compared in this paper. Based on the comparison, new diagnostic possibilities for atopic dogs are presented. PMID- 2264056 TI - [The endocrine status of clinically conspicuous mares during the peripartum period]. AB - The aim of the present investigations was to characterize the endocrine changes in the peripheral plasma during the periparturient phase of mares with a known history of obstetrical disorders. Blood plasma samples from 9 mares (8 mares during parturition, 1 mare during abortion) were collected and the following steroid hormones were radioimmunologically determined: progesterone (P4), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), estrone (E1), estrone sulfate (E1-S), estradiol-17 beta (E2), estriol (E3), cortisol and transcortin. In general, with the exception of cortisol, DHEA and transcortin, all steroid hormone levels declined significantly after parturition. Mean plasma concentrations of DHEA-S, the direct fetal precursor of estrone, were 6 times higher than DHEA. However, DHEA-S levels varied considerably between all mares as well as between daily values of the same mare. Levels of E1-S were found to be about thousand times higher than those of E1, E2, and E3. The rather low concentrations of E3 suggest that this hormone is mainly produced by peripheral conversion and that in the horse fetus the 16 alpha-hydroxylation of DHEA-S is lacking. Despite the fact that most of the examined mares showed signs of severe disease none of the investigated steroid hormones indicated any disturbances of gestation. It is concluded that, from the clinical point of view, serial determinations of E1-S plasma levels are the best way to prove the fetal well being. However, it should be stressed, that even the E1-S values are no indicators for the onset of parturition or abortion. PMID- 2264058 TI - [Helminth infections in wild boars in enclosures in southern Germany: species spectrum and infection frequency]. AB - To determine the helminth fauna of wild boars, stomachs and intestines of 124, lungs of 62, and livers of 39 animals from 5 enclosures in Southern Germany were examined. The evaluation of the species composition revealed at least 13 species: Metastrongylus apri, M. salmi, M. pudendotectus, Physocephalus sexalatus, Hyostrongylus rubidus, Globocephalus longemucronatus, Ascaris suum, Trichuris suis, Oesophagostomum dentatum, O. quadrispinulatum, Fasciola hepatica, C. tenuicollis and Capillaria. The most frequently isolated species was M. salmi with 91.9%, followed by G. longemucronatus with 91.1%, M. apri with 88.7%, M. pudendotectus with 87.1%, P. sexalatus with 51.6%, O. dentatum with 46%, T. suis with 30.6%, H. rubidus with 14.5%, A. suum with 12.1% and O. quadrispinulatum with 8.1%. Differences in the prevalence of infection, determined for animals up to 1 year old, 1-2 year-old and adults, were minimal for Metastrongylus spp. and G. longemucronatus. P. sexalatus, T. suis and A. suum, however, occurred more often in 1 year old, whereas H. rubidus, O. dentatum and O. quadrispinulatum were isolated more often from adults. A correlation of the infection rate with the sex of the animals was not found. PMID- 2264059 TI - Dose dependency of intratracheal elastase-induced changes in pressure volume curve and morphometry in rat lungs. AB - We studied the dose-dependency of the lung pressure-volume curve (n = 37) and morphometry (n = 30) with intratracheally administered elastase. Four weeks after elastase was instilled at dosages of 20 (EL-20), 40, 80, and 100 U/100 g wt., chord compliance between 50 and 70% of total lung capacity (TLC) (C50-70) and that between 80 and 100% TLC (C80-100) were measured. After a significant initial reduction, the weight of the EL-80 group recovered to the control level, whereas the weight curve of the EL-100 significantly decreased below that of the EL-80. Lung volumes of all the elastase-treated groups were significantly larger than those of control. Air-filled lung volumes monotonously increased when the elastase dose was increased from 20 to 80 U/100 g wt. In contrast lung volume of the EL-100 was significantly lower than that of the EL-80. On the other hand, liquid-filled lung volumes monotonously increased from 20 to 100 U/100 g wt. C80 100 was significantly smaller in the EL-100 than in the EL-80. The mean linear intercept increased and alveolar surface area decreased monotonously over the dose range tested. We conclude that there is a critical dose of elastase below which lung volume is increased and above which the increase is suppressed when elastase is administered intratracheally to Wistar rats. PMID- 2264060 TI - Intraoral minor salivary gland tumors: a demographic and histologic study of 200 cases. AB - In a demographic and histologic study of 200 intraoral minor salivary gland tumors seen in Japan (Nagasaki and Miyagi prefectures), 127 cases (63.5%) were classified as benign, comprising 124 pleomorphic adenomas and 3 monomorphic adenomas. The other 73 cases (36.5%) were malignant tumors, represented by 33 adenoid cystic carcinomas, 16 mucoepidermoid carcinomas, 10 carcinoma in pleomorphic adenomas, 6 acinic cell carcinomas, 5 adenocarcinomas, one polymorphous low-grade adenocarcinoma, one undifferentiated carcinoma and one clear cell carcinoma. There was an overall female preponderance (1.78/1). The mean age for females was 47.2 years and for males was 50.6 years. The mean age for patients with malignant tumors was 10 years greater than for patients with benign tumors and was statistically significant. The palate was the most common site for intraoral minor salivary gland tumors followed by the lip and buccal mucosa. These three sites accounted for 83% of all cases. Tumors arising in these three sites were predominantly benign. In contrast, those located in the gingiva, floor of the mouth and tongue were predominantly malignant. The results of this study were compared with other recent studies. PMID- 2264061 TI - Bimodality in the nocturnal behavior of the giant land snail, Achatina fulica. AB - Entrainment and phase advance of the circadian locomotor rhythms in the giant land snail, Achatina fulica, were examined by a running wheel method. The mean activity patterns in three light-dark (LD) cycles (LD 14: 10, LD12: 12, LD 10: 14) were characterized by bimodal peaks, namely an initial major peak 1-2 hr after the onset of darkness and a later peak after nearly 6 hr. The activity rhythms were able to follow a 6 hr phase advance shift of the LD 14: 10 cycle with transients, accompanied by shortening or splitting of the activity time. When splitting occurred, the initial component showed phase advancement in the dark and phased to lights-off whereas the later one phased to lights-on, with post-dawn activity being suppressed by light. These results suggest the presence of multioscillator circadian organization which shows monophasic or biphasic entrainment under the LD cycles. PMID- 2264062 TI - The determination of plasma intrinsic coagulant activity. AB - The increase in absorbance was traced during the coagulation of citrated plasma, while in contact with a plastic cuvette surface. The tracings gave rise to coagulation curves, which provided four values. The coagulation curve values were found to change by time due to contact with the surface of the tube containing the plasma. The rate of change was used to determine the intrinsic coagulant activity, in response to a weak activating surface. The value of the determination as a means for detecting hypercoagulability is discussed. The method was also used to study the effect of different factors affecting intrinsic plasma coagulant activity as; the surface of different tubes, plasma concentration, temperature of the tube containing the plasma and platelet concentration. PMID- 2264063 TI - Ubenimex treatment in congenital cyclic neutropenia. AB - A female patient with congenital cyclic neutropenia was presented. The cycle of neutropenia and the duration of neutropenia of less than 500/microliters was approximately three weeks and two weeks, respectively. There were also oscillations of monocytes and eosinophils with the peak level at the neutropenic phase. The severity and incidence of infections tended to diminish when the patient was pregnant. There were no abnormalities of lymphocyte subpopulations including CD4, CD8, CD4/CD8 ratio, and CD16. Administration of the immunomodulator ubenimex (Bestatin), 30 mg/day, reduced the severity of infections during the neutropenic periods, although the cyclic of neutropenia was not altered. PMID- 2264065 TI - Standardization of assays for testing the neutralizing ability of antivenoms. PMID- 2264064 TI - Repetitive sequences in the rat genome that have cleavage sites for the restriction endonuclease Taq I. AB - A cleavage of rat DNA with restriction endonuclease Taq I produced at least 8 discrete bands. One of the bands, 0.29 kilobase pairs (kb) long, was isolated and cloned in plasmid. The hybridization of this fragment to genomic DNA digested with Taq I showed 1.6 kb, 1.2 kb and 0.29 kb band in a smear hybridization signal. A repetition of the DNA sequence of this fragment was about 12,500 copies/haploid genome of both Buffalo and Sprague-Dawley rats by the Cot hybridization analysis. Four independent clones of 0.29 kb Taq I fragment share high homology (97%). PMID- 2264066 TI - Tetrodotoxin secretion from the lined moon shell Natica lineata in response to external stimulation. AB - The lined moon shell Natica lineata secretes tetrodotoxin (TTX) in response to an external stimulation such as removal from the seawater. The toxin released from the shellfish contained 14-361 mouse units of TTX per specimen. The shellfish did not secrete any further toxin when seawater removal was repeated over four times at about 1 hr intervals. All specimens recovered TTX secreting ability when they were kept in an aquarium for 5 days. PMID- 2264067 TI - Toxicity of Australian and French polynesian strains of Gambierdiscus toxicus (Dinophyceae) grown in culture: characterization of a new type of maitotoxin. AB - Gambierdiscus toxicus strains isolated from Australia and French Polynesia were grown in modified f2 and f10 nutrient media and the cells extracted for ciguatoxin and maitotoxin. The high nutrient enrichment of f2 media induced aberrant cell morphology in both strains whereas the majority of cells grown in f10 media had the typical lenticular shape of wild G. toxicus cells. The Australian strain grew faster and produced greater cell densities than the French Polynesian strain. Different chromatographic types of maitotoxin were extracted from the two G. toxicus strains and purified to homogeneity using reverse-phase high-performance liquid chromatography. The toxins elicited similar bioassay signs in mice, but produced different death-time vs dose relationships. The maitotoxin extracted from the Australian strain eluted later on both straight phase and reverse-phase chromatographic columns than did the maitotoxin extracted from the French Polynesian strain. The maitotoxin extracted from the French Polynesian strain was chromatographically identical to reference maitotoxin. For each strain no differences were found between maitotoxins extracted from cells grown in f2 or f10 media. Only one toxin was produced by each strain of G. toxicus. Ciguatoxin was not produced by either strain. PMID- 2264068 TI - In vivo interactions between neurotoxin, cardiotoxin and phospholipases A2 isolated from Malayan cobra (Naja naja sputatrix) venom. AB - The in vivo interactions between alpha-neurotoxin, cardiotoxin and two phospholipases A2 (sputa-phospholipase A2-1 and 3) isolated from Malayan cobra venom were assessed by examining the effects of simultaneous injection of sub LD50 dose of one toxin on (i) i.v. LD50 S of the other toxins in mice; and (ii) mean survival times of mice injected with lethal doses of the other toxins. While LD50 measurements did not reveal any interaction between the toxins in vivo, survival time measurements suggest a synergy between the neurotoxin and sputa phospholipase A2-1 and between sputa-phospholipase A2-1 and sputa-phospholipase A2-3. Our results also suggest that both sputa-phospholipases A2 interfere with the lethal action of the cardiotoxin, resulting in prolongation of the mean survival time of mice injected with a lethal dose of cardiotoxin. The patterns of in vivo interactions between phospholipase A2 and other venom toxins appear to depend on the nature and mode of pharmacological action of the phospholipase A2. PMID- 2264069 TI - The augmenting action of banana tree juice on skeletal muscle contraction. AB - An extract obtained from juice expressed from the stem of the plantain banana tree (Musa sapientum L., var. paradisiaca) induces twitch augmentation in skeletal muscles. The mechanism of this action was investigated in the mouse hemi diaphragm preparation. Directly evoked twitches and potassium induced (K+) contractures were both augmented by the extract. Twitch augmentation was partly dependent on extracellular Ca2+. The action on K(+)-contractures was unaffected by tetrodotoxin, but the rate of relaxation was enhanced in the absence of extracellular calcium (0[Ca2+]o). Muscle contracture induced by high concentrations of extract was also augmented in 0[Ca2+]o and in the presence of the Ca2(+)-channel blocking agent, nifedipine. The time course of the contracture was shortened in 0[Ca2+]o, but not by nifedipine. Nifedipine enhanced the augmenting effect of the extract on twitches but shortened the time-course of this action. In addition, a muscle contracture was superimposed on the twitching muscle at higher concentrations of nifedipine. Manganese, on the other hand, reduced or abolished the augmenting action of the extract. The results are consistent with an action of banana tree juice on the molecule responsible for excitation-contraction coupling in skeletal muscle, resulting in a labilization of intracellular Ca2+. PMID- 2264070 TI - Neuromuscular blocking activity of a glycosidic extract of the plant Sarcolobus globosus. AB - Crude glycoside extracts from the plant, Sarcolobus globosus, were tested on the rat phrenic nerve-diaphragm, chick biventer cervicis and frog rectus abdominis preparations. Nerve-stimulated twitches were inhibited by the extract. The muscle paralysis was not similar to that by curare-like blockers as it was not reversed by neostigmine or by a tetanus. Although contractures to acetylcholine or carbachol were not affected by 0.6 mg/ml of the extract, higher concentration of the extracts (3 mg/ml) depressed the log dose-response curve of acetylcholine and carbachol. The results suggest that the neuromuscular blocking effect of the extracts is either dose-dependent or due to a mixture of toxins with presynaptic or postsynaptic actions. PMID- 2264071 TI - Natural history of progressive ischemic stroke in a population treated with heparin. AB - Data on the acute natural history of progressive stroke with or without heparin treatment are limited. To define the acute course of patients treated with heparin for progressive stroke, we examined the charts of 69 such patients identified through the Cornell Neurology Database from October 1979 to June 1985. Analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables. Twenty-five patients (36%) continued to deteriorate while receiving heparin, another two (3%) worsened due to intracerebral hemorrhage, and a total of 10 patients (14%) had bleeding complications. No clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin. Clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time. Without unequivocal evidence demonstrating heparin's ineffectiveness for progressive stroke, many clinicians managing such patients will continue to use heparin. Our results suggest that this decision should not be governed by such clinical features as a patient's age or sex or by the vascular distribution of the stroke. Furthermore, frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome. PMID- 2264072 TI - The syndrome of bilateral hemispheric border zone ischemia. AB - Symptoms compatible with vertebrobasilar ischemia have been reported in patients with unilateral or bilateral carotid occlusive disease. Intracranial steal phenomena have been proposed to explain the symptoms. In a review of 54 patients with angiographically documented severe bilateral carotid stenosis (less than or equal to 2 mm residual lumen) or occlusion, eight had symptoms suggesting vertebrobasilar insufficiency. Five patients were identified retrospectively, and the other three were evaluated prospectively. Symptoms included various combinations of hemodynamically mediated, transient bilateral motor, sensory, or visual impairment. Dysarthria, dysphagia, and diplopia were generally absent. Each patient also described additional symptoms compatible with transient hemispheric or retinal ischemia. The anatomic regions subserving the bilateral vertebrobasilar-like symptoms could be correlated with angiographically estimated arterial border zones in both hemispheres and may thus represent bilateral hemispheric border zone ischemia rather than brain stem ischemia. An intracranial steal need not be invoked. PMID- 2264073 TI - Diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography. AB - The presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in Doppler ultrasound studies in vivo as well as in model carotid bifurcations. This flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood. We demonstrated the flow separation phenomenon on lateral-projection intra arterial digital subtraction angiograms in 99 of 100 carotid bifurcations. The mean duration of flow separation was 5.8 seconds, with values up to 14 seconds in normal carotid bifurcations. The presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia. Therefore, the angiographic finding of a flow separation has no diagnostic value. However, our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation, namely the duration of the stay of blood and its components within the area of flow separation. PMID- 2264074 TI - Transcranial color-coded real-time sonography in adults. AB - We investigated the diagnostic potential of transcranial color-coded real-time sonography in 52 individuals using a phased-array ultrasound system with color coded blood flow representation. Ultrasound scans in the axial and coronal planes were feasible through temporal acoustic bone windows in 49 subjects, enabling depiction of the main parenchymal and vascular structures as well as the ventricular system. Color-coded representation of blood flow in the cerebral vessels allowed unequivocal identification of the circle of Willis within the anatomic black-and-white B-mode image of the parenchymal structures. In Doppler mode, vascular blood flow phenomena may be analyzed semiquantitatively using the Doppler frequency spectrum. This noninvasive, serially applicable, mobile beside method may complement conventional neuroradiologic imaging methods, allowing on line studies of functional processes within the adult brain. PMID- 2264075 TI - Endothelium-independent contractions of human cerebral arteries in response to vasopressin. AB - We studied the effects of vasopressin in isolated segments from branches (500-700 micrograms in external diameter) of human middle cerebral arteries obtained during autopsy of 15 patients who had died 3-8 hours before. Paired segments, one normal and the other de-endothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. In 11 normal segments, vasopressin produced concentration-dependent contractions with an EC50 of 7.0 X 10(-10) M. Removal of the endothelium from 12 segments did not significantly affect vasopressin-induced contractions. Vasopressin produced further contractions in arterial segments with (n = 4) or without (n = 5) endothelium precontracted with KCl. In segments precontracted with prostaglandin F2 alpha, acetylcholine choline caused relaxation only of those with endothelium. At 10(-8) M (n = 11), the vasopressin V-1 receptor antagonist d(CH2)5Tyr(Me)AVP produced a 60-fold shift to the right of the control response curve for vasopressin. Increasing the concentration of the receptor antagonist to 10(-6) M (n = 7) further displaced the control curve in a parallel manner. These results indicate that vasopressin exerts a powerful constrictor action on isolated human cerebral arteries by direct stimulation of V-1 receptors located predominantly on smooth muscle cells. It appears that this contractile response is not modulated by the presence of an intact endothelial cell layer. PMID- 2264076 TI - Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type. AB - We performed clinical and neuroradiologic studies, including positron emission tomography, in five patients with vascular dementia of the Binswanger type. The clinical features of these cases consisted of slowly progressive dementia, together with vascular risk factors such as hypertension and often a history of minor stroke, and characteristic white matter lesions on brain computed tomograms or magnetic resonance images. Digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient. Both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter (54-77% of control values), and both were decreased in the parietal (73% of control), frontal (74-80%), and temporal (74-83%) cortices, where no abnormalities were detected by brain computed tomography or magnetic resonance imaging. We conclude that vascular dementia of the Binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter. PMID- 2264077 TI - Denervation in hemiplegic muscles. AB - This study examined the frequency of denervation activity in hemiplegic muscles in relation to the size and location of the central lesion. We studied 20 patients, 14 with major unilateral cerebral infarctions in the middle cerebral or internal carotid territories; four with a single lacune in the pons, internal capsule, or thalamus; and two with precentral infarcts. Using somatosensory evoked potentials, motor conduction studies, and assessments of conduction across the plexus and roots, we detected no conduction abnormalities on the affected side. Fibrillation was common in both groups, especially in distal and intermediate muscles. The distribution of the fibrillation and the normal conduction studies suggested that trauma of peripheral nerves was not a factor. Although the normal conduction studies and pattern of fibrillation activity do not exclude peripheral nerve trauma as the cause of the fibrillation, we suggest that transsynaptic degeneration is a reasonable alternative explanation. PMID- 2264078 TI - Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils. AB - We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1 pyramidal neurons measured 7 days after ischemia (28.4 neurons/mm, n = 10; control density in 10 naive gerbils 262.1 neurons/mm) and a significant decrease in forebrain calcium/calmodulin-dependent protein kinase II autophosphorylation measured 2 hours after ischemia (12.9 fmol/min, n = 6; control phosphorylation in six naive gerbils 23.5 fmol/min). The effect of temperature on these indicators of ischemic damage was examined by adjusting intracerebral temperature before and during the ischemic insult. Hyperthermic (39 degrees C) gerbils showed almost complete loss of neurons in the CA1 region (3.0 neurons/mm, n = 11) and extension of neuronal death into the CA2, CA3, and CA4 regions. In addition, hyperthermia exacerbated ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity (4.2 fmol/min, n = 6). Hypothermia (32 degrees C) protected against ischemia-induced CA1 pyramidal cell damage (257.0 neurons/mm, n = 20) and inhibition of calcium/calmodulin-dependent protein kinase II activity (26.0 fmol/min, n = 6). Our results are consistent with the hypothesis that loss of calcium/calmodulin-dependent protein kinase II activity may be a critical event in the development of ischemia-induced cell death. PMID- 2264079 TI - Elastic skeleton of intracranial cerebral aneurysms in rats. AB - In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin. PMID- 2264080 TI - Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. AB - Using in vivo brain microdialysis, we studied amino acid release in the striatum and cortex of eight rats following permanent middle cerebral artery occlusion. We then processed all brains for histopathologic assessment of the volume of ischemic damage 4 hours after occlusion. Ischemic damage was varied by occlusion of the middle cerebral artery at a point either proximal (n = 4) or distal (n = 4) to the lenticulostriate vessels. Proximal occlusion elevated the dialysate contents of all amino acids. The largest increases occurred for the potentially neurotoxic amino acids aspartate and glutamate and for taurine (800-2,800% of basal efflux). We observed smaller increases for the "metabolic" amino acids (280 580% of basal efflux). Distal occlusion did not affect amino acid efflux in the striatum, and release in the cortex was significantly lower than that following proximal occlusion. We compared release data with acute histopathologic outcome. Proximal occlusion resulted in a large volume of ischemic damage in the cortex and striatum (25-48% of hemispheric volume). A smaller volume of ischemic damage was noted following distal occlusion (0-21% of hemispheric volume). The volume of ischemic damage and the amount of amino acid release were significantly correlated (p less than 0.05). PMID- 2264081 TI - (S)-emopamil protects against global ischemic brain injury in rats. AB - (S)-Emopamil is a novel calcium channel blocker of the phenylalkylamine class, with potent serotonin S2 antagonist activity. We investigated the effect of (S) emopamil on the histopathologic consequences of global brain ischemia in anesthetized rats. Pretreated rats (n = 15) received 20 mg/kg i.p. (S)-emopamil 30 minutes before and 2 hours following 10 minutes of bilateral common carotid artery occlusion plus arterial hypotension (50 mm Hg). Quantitative cell counts following 3 days' survival revealed a marked loss of pyramidal neurons in all subsectors of the hippocampal CA1 area of untreated ischemic rats (n = 15). In contrast, in (S)-emopamil pretreated rats numbers of normal neurons were significantly higher, by 2.4-, 1.9-, and 1.8-fold, respectively, in the medial, middle, and lateral subsectors of the CA1 area. For example, normal neuron counts in the medial CA1 subsector were 34 +/- 9 (mean +/- SEM) in untreated ischemic rats compared with 82 +/- 13 in (S)-emopamil pretreated rats (control nonischemic value [n = 5] 157 +/- 2). By semiquantitative grading, (S)-emopamil also decreased ischemic changes in the cerebral cortex. No significant effect of (S) emopamil on ischemic injury was detected in rats treated beginning 30 minutes after the ischemic insult (n = 10). Thus, pretreatment with (S)-emopamil is beneficial in decreasing the severity of neuronal injury in global brain ischemia. PMID- 2264082 TI - Rupture of atheromatous plaque as a cause of thrombotic occlusion of stenotic internal carotid artery. AB - We analyzed the clinical profiles and autopsy findings of five patients who died shortly after developing cerebral infarction following thrombotic occlusion of the internal carotid artery. In all five cases, thrombotic occlusion was caused by rupture of the fibrous lining over the gruel of atheroma at the origin of the internal carotid artery showing tight stenosis of the lumen. The mean +/- SD shorter diameter of the lumen at the site of occlusion was 1.5 +/- 0.4 mm. Our results show that an internal carotid artery with tight stenosis of the lumen by atheroma containing gruel harbors a risk of thrombotic occlusion, which may give rise to cerebral infarction by artery-to-artery embolism or by reduced cerebral perfusion. PMID- 2264083 TI - Transcranial Doppler ultrasonographic assessment of intermittent light stimulation at different frequencies. AB - Seven normal adult volunteers underwent intermittent photic stimulation at frequencies of 5-60 Hz while their posterior cerebral arteries were monitored using transcranial Doppler ultrasound. Baseline measurements were obtained under conditions of total darkness, and sampling was also done during continuous illumination. Overall variation in mean flow velocity between complete darkness and continuous illumination was 9.8%, but the maximal change (expressed as percentage deviation from baseline) occurred consistently when stimulation was undertaken at frequencies of 10 (21%) and 20 (19%) Hz (p = 0.05). Frequencies higher than 20 Hz resulted in mean flow velocity variations that were not significantly different from that found during continuous illumination. The optimal frequency of intermittent visual stimulation required to induce measurable changes in posterior cerebral artery Doppler characteristics appears to be in the range 10-20 Hz. PMID- 2264084 TI - Sensory ataxic hemiparesis in thalamic hemorrhage. AB - Ataxic hemiparesis with cerebellar-like features has been reported following infarction or hemorrhage of the thalamus. We describe five patients with incoordination and corticospinal tract signs in the limbs opposite a dorsolateral thalamic hemorrhage. In four patients the hemorrhage extended superiorly into the lateral ventricle, the adjacent paraventricular region, and the upper and medial parts of the posterior limb of the internal capsule. Instead of cerebellar dysfunction, these patients exhibited directional errors of movement that improved distinctly when performed under visual guidance. We explain the incoordination on the basis of conscious deep sensory loss in the involved limbs. Perception of light touch, painful pinprick, and temperature were preserved in all patients. We use the term "sensory ataxic hemiparesis" to distinguish these patients from those with "classic" ataxic hemiparesis and cerebellar-like features, a distinction that may be important when planning functional rehabilitation. PMID- 2264085 TI - Pontine supranuclear facial palsy. AB - Two patients presented with a unilateral supranuclear facial palsy. Additional dysarthria was attributed to the pontine origin documented by magnetic resonance imaging on the contralateral side. The pontine disorder also was indicated by an isolated delay of the blink reflex R1 component or of the masseter reflex. We attribute the facial palsy to a lesion of a supranuclear fiber bundle supplying the facial nucleus. The location of the lesions favors these fibers taking a separate course from the main pyramidal tract at the mid- to upper pontine level. PMID- 2264086 TI - Intensity of anticoagulant treatment and risk of intracerebral hematoma. PMID- 2264087 TI - Lacunar infarction due to middle cerebral artery stenosis. PMID- 2264088 TI - Ileal mucosal expansion and colonic autotransplantation: sustained mucosal expansion. PMID- 2264089 TI - Cyclosporine toxicity in the small intestine. PMID- 2264090 TI - Comparison of omental and subcutaneous implantation after cryopreservation of fetal rat small bowel. PMID- 2264091 TI - Results of the perfusion and preservation of animal and human small-bowel transplant. PMID- 2264092 TI - Ex vivo normothermic perfusion of small-bowel grafts prior to transplantation. PMID- 2264093 TI - In vitro studies of intestinal lymphocytes following rat syngeneic intestinal transplantation. PMID- 2264094 TI - Experimental models in small-bowel transplantation. PMID- 2264095 TI - Surgical techniques for orthotopic intestinal transplantation in the rat. PMID- 2264096 TI - A comparison of heterotopic and orthotopic rat intestinal transplant models. PMID- 2264098 TI - Orthotopic small-intestinal transplantation: a human anatomic investigation and development of an animal model. PMID- 2264097 TI - Lymphatic regeneration after small-bowel transplantation. PMID- 2264099 TI - Segmental fetal small-bowel transplant: establishment of continuity with native small bowel in the rat. PMID- 2264100 TI - In vivo electrophysiologic evaluation of intestinal grafts in dogs. PMID- 2264102 TI - Metabolic changes and liver function after orthotopic small-bowel transplantation. PMID- 2264101 TI - Intestinal permeability and bacterial translocation following orthotopic intestinal transplantation in the rat. PMID- 2264103 TI - Effect of orthotopic small-bowel transplantation on vitamin A and zinc metabolism. PMID- 2264104 TI - Increased number of intraepithelial lymphocytes in rejected small-bowel allografts: an analysis of subpopulations involved. PMID- 2264105 TI - Histology and immunocytochemistry of transplanted rat small bowel. PMID- 2264106 TI - Ontogeny of natural killer activity in rat small bowel. PMID- 2264107 TI - Lymphocyte infiltration patterns in rat small-bowel transplants. PMID- 2264108 TI - Immunohistochemical analysis of immunocompetent cells involved in small-bowel rejection in the rat. PMID- 2264109 TI - What role for passenger leucocytes in small-bowel allografts? PMID- 2264110 TI - Graft-versus-host disease after clinical small bowel/liver transplantation. PMID- 2264111 TI - Irradiation of the donor combined with cyclosporine A treatment of the recipient prevents graft-versus-host disease and leads to prolonged survival of small-bowel allografts. PMID- 2264112 TI - Pathological changes following intestinal transplantation in the rat. PMID- 2264113 TI - Abrogation of lethal graft-versus-host disease in MHC disparate small-bowel transplantation in the rat by mesenteric lymphadenectomy. PMID- 2264114 TI - The effect of cyclosporine A in small-bowel transplantation in rats is dependent on the rat strain combination used. PMID- 2264115 TI - The influence of major histocompatibility complex subloci differences on graft rejection in small-bowel transplantation. PMID- 2264116 TI - Follow-up of small-bowel transplantation by monoclonal antibodies against brush border membranes. PMID- 2264117 TI - Immune responses during small-intestinal allograft rejection: correlation between procoagulant activity and histopathology. PMID- 2264118 TI - Major histocompatibility complex class II antigen expression on enterocytes during rejection of small-bowel allografts. PMID- 2264119 TI - Immune function in transplanted small intestine. II: sIgA production in cholera toxin-primed rats. PMID- 2264120 TI - Cyclosporine A vs cyclosporine A metabolites: comparisons of in vivo and in vitro immunosuppressive and toxic effects. PMID- 2264121 TI - The effect of donor-specific blood transfusions on orthotopic small-bowel transplantation in rats. PMID- 2264122 TI - Small-bowel transplantation following portal venous injection of donor strain spleen cells. PMID- 2264123 TI - Intestinal transplantation in children: contribution of immunohistochemistry. PMID- 2264124 TI - Experimental clinical intestinal transplantation: initial experience of a Canadian centre. PMID- 2264125 TI - Small-bowel transplantation in children. PMID- 2264126 TI - Successful clinical small-bowel transplantation. PMID- 2264127 TI - Immunohistochemical investigation of biopsies in a successful small-bowel transplantation. PMID- 2264128 TI - Structure of the major histocompatibility complex in the rat. PMID- 2264129 TI - Analysis of a nonclassical class I gene of the rat major histocompatibility complex. PMID- 2264130 TI - Cloning, expression, and evolution of rat classical and nonclassical class I genes. PMID- 2264131 TI - Variation in the biosynthesis of the rat RT1.Aa classical class I antigen due to the cim system. PMID- 2264132 TI - Endothelial target cell-dependent, differing patterns of chronic vascular renal allograft rejection in the rat. PMID- 2264133 TI - Immunogenetic analysis of rat kidney rejection. PMID- 2264134 TI - Host-versus-graft and graft-versus-host reactions occur simultaneously in fully immunocompetent recipients of class II disparate vascularized rat pancreas transplants. PMID- 2264135 TI - Nonendocrine pancreatic cells determine the immunogenicity of major histocompatibility class II-incompatible islets of Langerhans. PMID- 2264136 TI - Graft-versus-host reactions in immunocompetent allograft recipients: histopathology of an acute lethal syndrome after fully allogeneic major histocompatibility class II disparate organ transplantation in rats. PMID- 2264137 TI - Genetic requirements for the development of graft-versus-host reactions following small-bowel transplantation. PMID- 2264138 TI - Collapse curve clearance of transfused red blood cells in allogeneic rat strain combinations is a T-cell-dependent, but NK-independent phenomenon. PMID- 2264139 TI - Comparison of the effectiveness of cyclosporine A in small-bowel transplantation using different rat strain combinations. PMID- 2264140 TI - Anti-tubular basement membrane rejection nephropathy in rat kidney transplantation across multiple non-major histocompatibility complex alloantigenic differences. PMID- 2264141 TI - Polymorphism between rat T-cell alloantigens RT6.1 and RT6.2 is based on multiple amino acid substitutions. PMID- 2264142 TI - Expression of RT6 alloantigens and the T-cell receptor on intestinal intraepithelial lymphocytes of the rat. PMID- 2264143 TI - Lewis kidney grafts in RT4- and/or RT6-incompatible recipients. PMID- 2264144 TI - A maternally transmitted antigen system in the rat. PMID- 2264145 TI - Strain differences in alloreactivity in rats: the roles of T-cell subsets. PMID- 2264146 TI - Expression of blood group-related glycosidic tissue antigens on regressive and progressive variants of a rat colon carcinoma. PMID- 2264147 TI - Linkage group V esterases in the rat with special reference to ES-1. PMID- 2264148 TI - Computer program for the identification of quantitative phenotypes. PMID- 2264149 TI - HXB and BXH sets of recombinant inbred strains: strain distribution patterns of some genetic markers. PMID- 2264150 TI - Typing of inbred strains for RT3 and mapping of this antigenic system to linkage group X of the rat. PMID- 2264151 TI - Question of homology between rat chromosome 8 and mouse chromosome 9. PMID- 2264153 TI - Genetic hypertension is characterized by the abnormal expression of a gene localized in major histocompatibility complex HSP70. PMID- 2264152 TI - Identification of inbred strains of rats by DNA fingerprints using enhanced chemiluminescence. PMID- 2264154 TI - Complex genetic determination of the antitubular basement membrane disease in the rat. PMID- 2264155 TI - Genetic characterization of different diabetes-prone and -resistant BB-rat strains with special reference to RT6. PMID- 2264156 TI - Genetic susceptibility to the development of spontaneous insulin-dependent diabetes mellitus in the rat. PMID- 2264157 TI - Coat colour phenotype, leucopenia, and insulin-dependent diabetes mellitus in BB rats. PMID- 2264158 TI - Changes in phenotypical traits of inbred spontaneously diabetic BB rats: application of a computer-aided strategy. PMID- 2264159 TI - A new dwarf rat strain derived from a subline of BB/W rats. PMID- 2264160 TI - The hereditary hypertriglyceridemic nonobese rat: an experimental model of human hypertriglyceridemia. PMID- 2264161 TI - Spontaneous lymphoblastic leukemia in SD/Ipcv rats: transplantation and chromosomal analysis. PMID- 2264162 TI - A new rat model for polycystic kidney disease of humans. PMID- 2264164 TI - Genetic analysis of polydactyly-luxate syndrome in the rat. PMID- 2264163 TI - Autoantibodies in cyclosporine A-induced autoimmune disease. PMID- 2264165 TI - Diagnosis of rejection: role of fine-needle aspiration biopsy. PMID- 2264166 TI - [Diagnosis and treatment of metastatic spinal compression syndrome]. PMID- 2264167 TI - [Acupuncture analgesia. Neurochemical and neurophysiologic aspects]. AB - In some parts of the world, acupuncture has been employed as a method of obtaining analgesia for thousands of years without the mechanism of its action being understood. During the past two decades, evidence has accumulated indicating that acupuncture activates an intrinsic neural network which monitors and modifies the activity of pain-transmitting neurons. The in-suppressing action is partly mediated by endogenous opioid peptides and monoamines. The system is organized at three levels of the neuroaxis: spinal cord, medulla and the midbrain. The raphe magnus nucleus and the spinal cord constitute a fundamental circuit while the PAG funnels the influences from the more rostral structures and collects information from the spinal cord. PAG initiates descending and ascending nihibition resulting in the reduction of pain. The endogenous pain-control system may be elicited by other physiological stimuli and the effect of acupuncture is scarely specific. PMID- 2264168 TI - [Phenacetin, paracetamol and bladder cancer]. AB - Every year great quantities of analgesics of various kinds are employed in Denmark. Among the preparations previously employed, considerable evidence has been found that phenacetin-containing combination analgesics can produce cancer in man while there is limited evidence that phenacetin alone can produce cancer. Combination analgesics containing phenacetin increase the risk of development of tumours in the renal pelvis. This is a rare form of tumour with certain etiological features in common with tumours of the bladder. It may appear probable that phenacetin also increases the risk of development of cancer of the bladder but review of the literature provides only limited evidence of this. The possible carcinogenic effect of paracetamol in man is only sparsely illustrated. No reports about an increased risk for cancer of the bladder are available. Phenacetin was withdrawn from the Danish market on 1.1.1985 on account of the suspected carcinogenic effect. Since 1977, the sale of paracetamol (acetaminophen) which is also a breakdown product of phenacetin has been increasing steadily. PMID- 2264170 TI - [Mortality of severe asthma in Danish intensive care units in 1988. A questionnaire study]. AB - The mortality due to asthma is gradually increasing in Denmark. In 1988, 209 patients died from asthma. Of these patients, 108 were under 70 years. Information about patients who died from asthma in Danish intensive care units (ICU) in 1988 was obtained retrospectively by questionnaires. 99% of all the ICU's replied. Eleven of the abovementioned patients died in an ICU because of inadequate oxygenation or ventilation. In cases where an anaesthesiologist was called to a patient with acute severe asthma, who subsequently died from the disease, the majority had developed cardiac arrest, when the anaesthesiologist arrived. The use of objective monitoring of the degree of pulmonary obstruction by use of peak flow measurements and series of arterial blood gas values is recommended. Hypoxemia, the main risk factor, might be revealed in time by measurements of pulseoximetry. If the arterial PCO2 is increasing, the patient should be monitored in an ICU in view of oxygenation and ventilation, and possibly mechanical ventilation. PMID- 2264169 TI - [Metastatic spinal compression syndrome. Symptoms, diagnosis, treatment and prognosis]. AB - A retrospective study of 398 patients suffering from metastatic compression of the spinal cord or cauda equina is presented. The study comprised almost all relevant medical records of patients admitted to hospital in the eastern part of Denmark in the period 1979 through 1985. Carcinoma of the lung, prostate, breast and kidney were the most frequent primary malignancies causing spinal compression. Most patients were treated with laminectomy, or radiotherapy or with laminectomy and radiotherapy combined. The effect of the treatment was estimated by evaluation of motor function and sphincter control. Treatment with laminectomy followed by radiotherapy was significantly superior to treatment with laminectomy or radiotherapy alone. But if the patients' motor function and primary tumour were taken into account, no significant difference between the treatments was observed. The efficacy of treatment depended upon the symptoms when the diagnosis was established, and accordingly early diagnosis is of the utmost importance. The incidence of metastatic compression increased during the period covered by the study, and since this condition must not go untreated, awareness of the symptoms, primarily pain, is essential. PMID- 2264171 TI - [Arthrosis of the lower limb and running]. AB - In order to assess whether running training for many years predisposes to arthrosis in the lower limbs, the hips, knees and ankle joints of 30 runners who began running training at the beginning of the nineteen fifties were examined. Three of these runners were no longer active. One of these had given up late in the nineteen seventies on account of arthroses in the upper and lower limbs i.e. changes which can scarecely be attributed to the stresses of running. The remaining 27 (90%) had run 20-40 km/week throughout 40 years. Subjective, objective and radiological data were compared with data from 27 non-active control persons who were comparable as regards age, weight/height and occupational stress with the runners. We found no differences in joint mobility, axial deviations or complaints of pain between the two groups. Radiologically, the distances between the osseous joint surfaces in the hip and ankle joints and the degrees of degeneration in the knees were assessed according to Ahlback's classification without any differences being found between the groups. Our results suggest that running training to a moderate extent for many years does not predispose to arthrosis in the lower limbs in healthy individuals. PMID- 2264172 TI - [Mediastinal infection following open heart surgery]. AB - A retrospective investigation was undertaken of the mediastinal infections in patients submitted to cardiac surgery. A total of 1,763 patients participated in a period of 11 years from 1978 to 1988. All of the case records were reviewed for the occurrence of infections in the mediastinum and 24 patients (1.4%) were found to have had mediastinitis. Predisposing factors to mediastinal infections are reviewed. In all of the cases, treatment consisted re-thoracotomy with removal of all necrotic and infectious material. This was followed by primary closure over a retrosternal irrigation system which supplied an antibiotic solution for six days. In addition, oral antibiotics were administered on the basis of the findings on culture. The incidence of infection was found to be increased when the left internal mammary artery (LIMA) had been employed and in cases of combined cusp and coronary surgery. In 20 patients (83%), relevant culture findings were found from the mediastinal drain on an average of 2.5 days after the primary operation. These were reencountered in the mediastinum at rethoracotomy which was performed on an average of 15 days after the primary operation. This raises the question of the possibility of earlier intervention. The commonest microorganisms were micrococci and Staphylococcus aureus which together comprized approximately 83%. The antibiotic treatment routinely employed was 1 g meticillin four times daily. Five patients died (21%) and 19 patients were discharged. On follow-up examination, the sternum was stable and the scar healed. When infection in the mediastinum is suspected after cardiac surgery, early diagnosis and active surgical treatment are important. The closed method of irrigation drainage is recommended by the authors. PMID- 2264173 TI - [Technology use in connection with delivery in Danish maternity departments]. AB - With the object of obtaining information about the technology use employed in Danish maternity departments, a questionnaire was sent to the 58 maternity departments which existed in Denmark in May 1989. These maternity departments covered 99% of the 55,660 births in Denmark (in 1987). Deliveries at home (a total of 511) and delivers in departments with less than four deliveries annually (a total nine) were responsible for the remaining 1%. 100% of the departments returned a completed questionnaire. The following percentages are based on the deliveries included in this investigation. The review revealed that 93.5% of Danish women are delivered in departments with access to carditocographic equipment (CTG), 34% in departments where this is offered routinely to all parturient women. Sixteen departments which did not possess CTG equipment all had fewer than 400 deliveries per annum and 12 of these stated that they wished they had had CTG. Only four of the 58 maternity departments (managing 3.4% of the deliveries in 1987) never employ human placental lactogen (HPL) or oestriol (O3) analyses. The most commonly employed hormone parameter is HPL which is undertaken on appropriate indications in 51 of 54 departments and routinely in the remaining three. Scalp-pH is carried out in 13 of the Danish maternity departments. Thus 41.7% of all the parturient women have access to this analysis. However, only 20% are delivered in maternity departments where this test is employed frequently. Cord-blood-pH is employed routinely in 31.7% of the neonates. Measurement of intrauterine pressure is employed in six out of the 58 maternity departments which are responsible for 25% of Danish deliveries. It is concluded that the slightly increased employment of technology use during delivery in 1989 as compared with practice in 1984 may primarily be due to the closing of several small maternity units during the past five years. In general, the use of technologies are less intensive than in England, Germany, France and the USA. PMID- 2264174 TI - [Induction of labor. Prostaglandin E2 vaginal tablets compared with intravenous oxytocin for induction of labor in premature rupture of the membranes and immature cervix]. AB - In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer. PMID- 2264175 TI - [Observation and follow-up of premature rupture of the membranes. A pilot study of women at term with immature cervix and premature rupture of the membranes, without contractions]. AB - In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer. PMID- 2264177 TI - [Torsion of an omental cyst. A rare cause of abdominal pain in children]. AB - A case of torsion of an omental cyst in a boy aged three years is described. Operation was undertaken for suspected appendicitis. As a rule, the diagnosis is established during operation. If the condition is suspected clinically, the diagnosis may be established by ultrasonography, computed tomography or magnetic resonance. Treatment of omental or mesenteric cysts is always surgical. PMID- 2264176 TI - [Delayed pushing and frequency of vacuum extraction in deliveries under lumbar epidural analgesia]. AB - With the object of reducing the high of vacuum extraction in deliveries with lumbar epidural analgesia, we introduced "late pushing" in these deliveries in 1988. By this is understood that the parturient women is first encouraged to push when the orifice is completely dilated and the infant's head is visible at introitus. Before the "late pushing" was introduced, the frequency of vacuum extractions in deliveries with lumbar epidural analgesia was 44% of the vaginal deliveries. During the period of investigation, the frequency was 43%. Introduction of the "late pushing" thus did not result in any alteration (p greater than 0.4). Parturient women with lumbar epidural analgesia and slow progression of labour differed from the remainder of the parturient women with lumbar epidiral analgesia by significantly higher birth weights (4,000 g as compared with 3,400 g) and this may explain the increased frequency of vacuum extraction in this particular group of parturient women. The authors consider that lumbar epidural analgesia has the advantage that delivery is less painful for the mother without any simultaneous increased risk for the infant. PMID- 2264178 TI - [Lithium therapy and renal function]. PMID- 2264179 TI - [Thyroid gland surgery]. PMID- 2264180 TI - [The national medical journal--what for?]. AB - National medical journals constitute one of the most visible links which unite the medical profession despite specialities and types of employment. In addition to being informative, instructive, supplying comments and, best of all, entertaining, medical journals have also the responsibility for the professional identity of doctors and development of the roles they play. With their circulation end significance, national medical journals are representatives for culture in the medical world. The Nordic journals have particular tasks as regards the national professional terminology and the national professional environment. The future main challenges for general medical journals will be adjustment to the expectations from the media of the new generations of doctors, clarification of the relationships between journals as organs for qualification and informative channels, and ensuring editorial independence. PMID- 2264182 TI - What actually happened: international cooperation among medical journals. PMID- 2264181 TI - The task of the medical editor. PMID- 2264183 TI - [The importance and conditions of the freedom of expression]. PMID- 2264184 TI - [Physician's role, text hygiene and speech culture]. PMID- 2264185 TI - [The humanitarian duty--a challenge to the privileged]. PMID- 2264186 TI - [A disease of the society--on minorities and human rights]. PMID- 2264187 TI - [Inflammation as a basic biological mode of reaction]. AB - The inflammatory reaction is a fundamental biological defence reaction which ensures the survival of the organism. Reaction of the organism to trauma includes local and systemic reactions which are integrated and which are often the basis for the clinical and paraclinical manifestations of disease. The reactions of the organism to trauma are, by and large, nonspecific and independent of the nature of the precipitating factor. This explains the similarity between the clinical and paraclinical manifestations in a series of inflammatory diseases. The basal inflammatory reaction pattern may be identified in apparently very different conditions: healing of wounds, infectious disease, non-infectious inflammatory disease, atherosclerosis, neoplastic disease and growth and regeneration. Identification of a series of humoral inflammation mediators and growth factors and the possibilities for direct monitoring of the inflammatory and reparative processes of connective tissue have increased the possibilities for identification of the etiological/pathogenetic factors and the possibilities for rational therapeutic pharmacological and immunological modulation of disease. PMID- 2264188 TI - [Chronic inflammatory bowel disease--status over 30 years of research and development]. PMID- 2264189 TI - [One step forward, one step back. Research policy in the 1990's--a link in a historical sequence]. AB - A description is presented of the major problems in Danish research in the nineteen nineties, including internationalization, competition, concentration, training of research workers, transparency, connections with the surrounding community and ability of drawing conclusions. Elements in the Danish research system and the research policy are described. Connections are then made with the situations at the end of the nineteen sixties and beginning of the nineteen seventies when the new research council established a considerable part of the basis upon which we build today. Finally, freedom in research and the responsibilities of research and research workers for the community are mentioned. PMID- 2264190 TI - [Future medical research]. AB - Medical progress requires a well-balanced research effort in a number of different fields, and this paper lists those types of research which will be needed in the future. The author analyses the foundation of clinical decisions and stresses the importance of continued biological laboratory research and controlled clinical studies. He also stresses the need for new types of research such as quality assurance, medical audit and humanistic studies (qualitative research, descriptive ethical studies and philosophical enquiries). PMID- 2264191 TI - [Validity of qualitative research]. PMID- 2264193 TI - [Is it a moral obligation to be an organ donor or a subject for experimentation?]. PMID- 2264192 TI - [From legislative etiquette to medical ethics. The course in Denmark from 1945 to 1990]. PMID- 2264194 TI - [The scientific ethics committee system]. PMID- 2264195 TI - [Iceland and the Scandinavian cooperation within health care and social service]. PMID- 2264197 TI - [The physician and music]. PMID- 2264196 TI - [Undergraduate medical education--vacuum, growing pains or vision? Study plans at the University of Copenhagen]. AB - Establishing the 1986 study plan in the medical faculty in Copenhagen took ten years. This study plan fulfilled most of the requirements of the medical curriculum proposed by the National Professional Committee in 1976. A particularly positive feature was emphasis on clinical subjects as compared with conditions in the 1967 plan. The absence of priority awards for the specialist subjects resulted in a total increase in the curriculum of 12% with the risk of prolongation of the course or increasing the number of drop-outs. Qualitatively, overfilling of the study plan with scheduled subjects may result in deterioration, as time for more intensive study of the subjects and participation in bedside teaching is reduced. Considerable reduction in scheduled teaching and in the curriculum, particularly theoretical lecturing, which is soon outdated, is recommended. Instead, greater emphasis should be laid on individual training in solving problems and search for knowledge, training in clinical skills, and attitudes which ensure that future generations of doctors have a critical scientific approach and responsibility and care for their patients. PMID- 2264198 TI - [The late results of the combined treatment of kidney cancer patients]. AB - Randomized study with inclusion of certain types of immunotherapy in the schedule of complex treatment was conducted in 89 patients with kidney carcinoma after the operation. In 63 patients the tumor was in stage T3N0M0. The patients were separated into 4 groups after the operation. Group 1 consisted of 23 patients in whom no additional therapeutic measures were applied in the postoperative period; 8-year survival was 48%. Group 2 was made up of 23 patients who received immunotherapy with the BCG vaccine in the postoperative period; 8-year survival was 60.5%. Group 3 consisted of 9 patients who were given levamisole for immunotherapy in the postoperative period; 8-year survival was 44%. Group 4 consisted of 8 patients who were treated by a combined method in the postoperative period: administration of the BCG vaccine, a placental suspension, and cyclophosphamide; 8-year survival was 75%. Multiple metastases occurred in 26 patients. Nineteen patients did not receive additional treatment in the postoperative period; 2 patients survived for 1 year, none of the patients lived longer than 2 years. Seven patients were given immunotherapy with the BCG vaccine in the postoperative period; 6 patients survived 1 year, 4 patients--2 years. Measures for increasing the activity of the immune and macrophagal systems should be included in the schedule of complex treatment for patients with carcinoma of the kidney. PMID- 2264199 TI - [The free amino acid content of the blood serum in bladder cancer patients]. AB - The content of 18 amino acids in the blood serum was studied in 57 patients with T2-4 carcinoma of the bladder according to the stage of the process and the functional condition of the kidneys. Dysaminoacidemia was found in patients with T2 bladder carcinoma, which did not need correction; marked hypoaminoacidemia was encountered in stage T3-4 tumors. Chronic renal insufficiency (intermittent and terminal stages) is conductive to significant decrease of the blood amino acid level. The content of amino acids is lower in the postoperative than in the preoperative period. The degree of reduction of the amino acid content in blood was found to be dependent on the volume of the operation. The reduction of the amino acid content is more intense after cystectomy than after resection of the bladder. Correction of the blood amino acid content in the preoperative period in patients with T3-4 carcinoma of the bladder reduces the incidence of postoperative complications. Correction of hypoaminoacidemia with polyamine proves effective in patients with maintained renal nitrogen excreting function. In development of azotemia in patients with bladder carcinoma, substitution transfusion therapy for correction of hypoaminoacidemia becomes effective only after restoration of the nitrogen excreting function of the kidneys. PMID- 2264200 TI - [The procedure for treating kidney cancer patients with metastases to the bones]. AB - Active surgical intervention in patients with kidney carcinoma and metastases in the bones helped in prolonging the life of previously doomed patients for several years. Of course, we are far from the idea that such tactics is justified in all patients. An individual approach is necessary. The fundamentals of successful treatment is thorough diagnosis. The extent of the neoplastic process cannot always be determined, errors are often made in establishing the diagnosis, which leads to faulty choice of the therapeutic tactics. PMID- 2264201 TI - [The combined treatment of urinary incontinence after adenomectomy]. AB - Treatment was applied in 55 patients with enuresis after removal of adenoma of the prostate. Nonoperative treatment of 46 patients included therapeutic exercises, drug therapy (anti-inflammatory agents and tonics), and physical methods: transurethral direct electrical stimulation of the vesical sphincters (25 patients), transperineal ultrasonic stimulation (21 patients). After nonoperative treatment enuresis was completely cured in 31 patients. Fifteen patients with poor results were subjected to a second course of treatment: a satisfactory result was produced in another 6 patients, an improvement was recorded in 9 patients. Operative treatment was carried out in 9 patients: 4 of them by A. Puigvert's method (satisfactory result in 1, improvement in 1, poor result in 1, acute ischuria in 1) and 5 by a modified Puigvert's operation the techniques of which consisted in forming 2 rectangular grafts from the tunica albuginea of the cavernous bodies of the penis, suturing the medial grafts to one another above the urethra on the midline, and suturing to their bases the lateral grafts (satisfactory results in 4, improvement in 1). Thus, complex treatment of 55 patients for enuresis consequent upon removal of adenoma of the prostate caused a satisfactory result in 42 (76.4%), an improvement in 11 (20%), and a poor result in 2 (3.6%) patients. PMID- 2264202 TI - [Changes in the beta 2-microglobulin level during hemodialysis]. AB - The authors studied changes of the beta 2-microglobulin level during hemodialysis with dialyzers AIP-02-02 (cuprophane membrane), E2 (cuprophane membrane), AIP-03 02 (polysulfone membrane), F60 (polysulfone membrane), and hemodiafiltration with dialyzer F60. The following data were obtained. The beta 2-microglobulin level in patients undergoing hemodialysis is approximately 20 times the normal level. No essential fluctuations of the level of this protein occurs during hemodialysis and hemodiafiltration. The cuprophane membrane does not cause increase of beta 2 microglobulin generation during hemodialysis. Standard hemodialysis with the cuprophane membrane and the highly-permeable polysulfone membrane does not lead to decrease of the beta 2-microglobulin level. Hemodiafiltration with the highly permeable polysulfone membrane is an effective method for the elimination of this protein. PMID- 2264203 TI - [Ultrasonic study in the diagnosis of developmental defects and diseases of the urinary system in children]. AB - Echography has recently become one of the leading methods of examination in different branches of medicine. Despite its high informativeness, however, it is not used widely in pediatrics. The article generalizes the practical experience accumulated in ultrasonic examination of urinary organs in children with developmental anomalies and diseases of the kidneys, ureters, urolithiasis, and Wilms' tumor. Besides, the possibility of echography as a screening test in outpatient examination of children with changed values of urinalysis is shown for the first time in pediatric practice. The authors describe the advantages of the method in combined developmental anomalies and regular medical examination of patients after various methods of treatment. They emphasize its merits (absolute safety, no injurious effect, high informativeness, the possibility of performing it in children who are in a grave condition, its extensive use under outpatient conditions, etc.). It is shown the ultrasonic examination in outpatient clinics makes it possible to divert from the traditional plan of radiourological examination of children, which includes excretory urography performed in children in inpatient clinics as a rule. It is obvious that the use of echography as a diagnostic test will make it possible to exclude the radiation load which is most harmful for the growing and developing organism and will not require mass hospitalization, which will undoubtedly have a high therapeutic and economical effect. PMID- 2264204 TI - [The effect of heparin on the lipid level during hemodialysis]. AB - The level of free fatty acids, triglycerides, and total lipids was studied in dynamics during hemodialysis. At the beginning of hemodialysis, fatty acids are discharged into the blood flow and their level at 20 min of hemodialysis is three fold the initial level. Plasma triglycerides, which are components of lipoproteins, are the source of the discharge of free fatty acids. This is confirmed by the fact that the triglyceride content reduces simultaneously with the increase in the level of free fatty acids. The concentration of total lipids practically does not change during hemodialysis. The possible significance of a sharp increase of the free fatty acid level during hemodialysis is discussed. PMID- 2264205 TI - [A comparative evaluation of the central hemodynamic indices in patients with the terminal stage of kidney failure during dialysis therapy and allografting]. AB - Changes of the functional indices of central and intracardiac hemodynamics during treatment with hemodialysis or peritoneal dialysis, as well as after cadaver kidney transplantation, were studied in 44 patients with the terminal stage of chronic renal failure by means of radiocardiography with 131I-albumin. The signs of cardiac insufficiency were evaluated according to the classes of the cardiologists' New York classification accepted in 1964. Four groups of patients were distinguished during the analysis: group 1-10 patients given intravenous detoxification therapy; group 2-19 patients treated by chronic programmed hemodialysis; group 3-4 patients kept on peritoneal dialysis; group 4-11 patients after allotransplantation of cadaver kidney. It was found that in group 1 patients the indices of central (mean arterial pressure, cardiac and stroke indices, total peripheral vascular resistance, work of the left ventricle) and intracardiac (time of circulation of blood in the heart cavities and lungs) hemodynamics were on the upper normal values and in occasional cases exceeded it. In patients of group 2 the indices of intracardiac hemodynamics grew worse and required an individual approach to the hemodialysis regimens with due account for the volemic disorders. In group 3 some indices of central and intracardiac hemodynamics corresponded to those in group 2, but the circulation volume, and mean arterial pressure were normal, which was reflected by better subjective tolerance to peritoneal dialysis. Analysis of indices in group 4 patients showed improvement of normalization of most parameters of central and intracardiac hemodynamics with gradual increase of diuresis, and abatement of the clinical signs of cardiac insufficiency after successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264206 TI - [Functional disorders and immunological changes in the thyroid of children with acute and chronic glomerulonephritis]. AB - Studies showed that equivocal shifts occur in the functional condition of the thyroid in children with various clinical syndromes of acute glomerulonephritis and clinical forms of chronic glomerulonephritis. For instance, signs of increased functional activity of the thyroid are encountered in children with the nephritic syndrome of the acute and hematuria form of chronic glomerulonephritis, and signs of diminished thyroid function occur in patients with the nephrotic syndrome of the acute and nephrotic form of chronic glomerulonephritis, evidence of which are the corresponding changes of the content of protein-bound iodine and thyroid hormones in the blood serum. No essential changes are revealed in the functional condition of the thyroid in other syndromes of acute and forms of chronic glomerulonephritis. At the same time, signs of immunopathological changes of the thyroid are revealed in patients with various syndromes of acute and forms of chronic glomerulonephritis; these are manifested by the appearance of antithyroid antigens in the blood and increase of the neutrophil injuriousness index in the test with the antigen of this organ. The obtained data indicate that in planning complex therapy of children with glomerulonephritis due regard should be given to involvement of the thyroid in the pathological process and the character of its functional disorders in concrete clinical syndromes of acute and clinical forms of chronic glomerulonephritis. PMID- 2264207 TI - [The urinary excretion of renal prostanoids in children with chronic obstructive pyelonephritis in vesicoureteral reflux before and after antireflux operations]. AB - The excretion of renal prostaglandins (PGE, PGF2 alpha, 6-keto-PGE1 alpha and TKB2) was studied in 45 children with chronic obstructive pyelonephritis in the presence of vesicoureteral reflux with account for the disease stage (partial remission--group I; total clinical and laboratory remission--group II) in various periods of surgical corrections of the impaired urodynamics in the area of vesicoureteral segments (in the early postoperative period of 12-14 days after the surgery; in the follow-up period of 6-12 months after the surgery). Preoperative observation of Group I children revealed a significant decrease in urinary PGF2 alpha excretion in the presence of an increase in the circadian TKB2 and 6-keto-PGF1 alpha excretion, whereas the patients from Group II who had normal levels of TKB2 and 6-keto-PGF1 alpha excretion, the levels of PGE and PGF2 alpha were lowered. The retention of sodium was documented in both groups. There was a total recovery of renal sodium and water excretion 6-12 months after the surgery. Children without the urinary syndrome (group II) demonstrated normalization of all secreted prostanoids, whereas in those with pronounced severity of pyelonephritis (group I), the excretion of sodium and diuresis were likely to be provided by hyperproduction of vasodilating sodium and diuretic PGE. PMID- 2264208 TI - [An experimental study of the energy metabolism in the cortex of the single denervated kidney]. AB - The long-term study of intratissular contents of ATP, ADP, AMP and the energy charge of the renal cortex in rats under the conditions of experimental combination of compensatory hypertrophy and chronic nervous decentralization enabled the authors to make the conclusion on the chronic energy-deficient status of the tubular cortical zones manifest by a two-wave decrease in the pool and the impaired spectrum of the adenyl system constituents. A negative trophic effect of demediatorization of chronically overloaded tissue of the cortex was found to be responsible for the disorders in the energy metabolism levels in the early phase of the disease and two months later for the progressive hypoperfusion of the cortical tubular system of a single denervated kidney. PMID- 2264209 TI - [Elephantiasis of the external genitalia in children]. AB - This study presents an experience with diagnosis and management of external genital elephantiasis in 18 children in the age range of 3 to 15 years. All patients underwent surgical treatment. The type and scope of surgery depended on the extent and severity of elephantiasis. A total of 21 operations were done. Long-term results were evaluated in these 13 patients at 1 to 22 years. The evaluation included physical appearance of the genitalia, scars, secondary deformities, penile and testicular size, the presence of erections and menstruation. Adults of mature ages were evaluated for fertility and reproductive status. Long-term results were good in all 13 patients. This analysis suggests that early radical surgical treatment of children with congenital elephantiasis of the external genitalia enables a normal anatomic and functional genital development and averts severe local and systemic disorders. PMID- 2264210 TI - [The pathogenesis of hydrocele]. AB - Hydropic fluid in hydrocele was studied for physicokinetic properties on whose basis an attempt was made to explain the pathogenetic mechanism responsible for dynamic fluid collection in the disease. A total of 45 patients with idiopathic hydrocele whose duration was an average of 4 years were examined. In the majority of cases, the disease was secondary to scrotal injuries. The authors determined hydropic fluid viscosity, hydrostatic pressure in the hydrocyst, total protein levels in the serous fluid, and intensity of hydrocyst absorption of methylene blue after its prior administration into the hydrocyst. The hydrostatic pressure in the hydrocyst, the total protein content, and the viscosity of the serous fluid were found to be directly proportional to each other. The intensity of serum methylene blue absorption was higher, its concentration being lower in most cases than in health. Thus, the pathogenesis of hydrocele seems to be as follows. In imbalance of serous fluid exudation and absorption flows as a consequence of lymphostasis and venous congestion, its collection starts in the vagina, which is accompanied by an increase in the hydrocyst's volume and an elevation of its hydrostatic pressure. With this, microcirculatory abnormalities deteriorate as a result of impaired vascular wall permeability, which causes a change in the composition of the serous fluid and an increase in its viscosity. The elevated hydrostatic pressure results in higher viscosity of the serous fluid, vice versa. Finally, this thermodynamic self-developing system will convert to a new equilibrium state with the established viscosity, pressure, temperature that ensure a balance of flows. PMID- 2264211 TI - [The transplantation of 2 ureters to a single lateral bladder flap in recurrent stone in the split (doubled) ureter]. PMID- 2264212 TI - [Xanthogranulomatous calculous pyelonephritis resulting in pyonephrosis and paranephritis]. PMID- 2264213 TI - [Actinomycosis of the kidney]. PMID- 2264214 TI - [Primary actinomycosis of the kidney]. PMID- 2264215 TI - [Complications in excretory urography]. PMID- 2264216 TI - [Tamm-Horsfall protein: its pathogenetic role and clinical significance in urologic and nephrologic diseases]. PMID- 2264218 TI - [Endothelium of the donor's transplant after penetrating keratoplasty]. AB - The results of a follow-up of changes in the transplant endothelial cells in 208 patients (209 eyes) in the periods from 1 week to 5 years after surgery helped the authors define the criteria for the choice of donor material with consideration of the endothelial status for various groups of patients. They suggest a method for differential diagnosis of tissue incompatibility reactions and infection recurrences in patients who were operated on for herpes virus keratoiridocyclitis by means of reflecting biomicroscopy of the endothelium. The minimal count of cells necessary for the transplant to remain transparent was estimated. PMID- 2264217 TI - [The urodynamics of the lower urinary tract after reconstructive operations in bladder exstrophy]. AB - The results of plastics of the bladder with local tissues in its exstrophy in 34 children were appraised according to the findings of clinical, functional, and morphological studies. The cosmetic effect was satisfactory in 22 patients, but control over urination remained unsuccessful as a rule. Enuresis after sphincteroplasty was linked with functional insufficiency of the trigonal muscle due to tissue dysembryogenesis. Another component of enuresis was dysfunction of the bladder attended by intravesical hypertension and uninhibited contractions when its size was small. The results of morphological studies allowed the authors to explain the character of the urodynamic disorders and the inefficacy of their nonoperative correction. PMID- 2264219 TI - [Use of fresh amnion in the treatment of corneal diseases]. AB - The effects of fresh amnion on the course of morbid processes in corneal ulcers and burn disease of the anterior segment of the eye were investigated. The cornea was coated with amnion in 15 eyes with deep bacterial ulcers, in 10 eyes with herpetic ulcers of the cornea, and in 8 eyes with second and third-degree corneal and conjunctival burns. The amnion was obtained in cesarean section and fixed to the limbal conjunctiva with an uninterrupted suture all around. The next day after surgery the pain syndrome reduced, as did photophobia and blepharospasm in all the patients. In the group of patients with bacterial ulcers the cornea epithelialized on days 5-11, in those with herpetic ulcers on days 10-15, and in those with burns on days 8-12 after amnion coating. No cases with suppuration of the burnt surface when coated with the amnion were recorded. The amnion slid off the cornea on days 7-10 after it was layered on. PMID- 2264220 TI - [Significance of topographic diagnosis of foreign bodies situated in the orbit]. AB - Clinical picture of extraocular foreign bodies in the orbit is analyzed in 49 patients, specific features of the diagnosis and treatment of this condition are discussed. Study of the topography of foreign bodies in the orbit has helped distinguish the clinically significant area of fragment localization, areas at a high risk of developing complications, and 'quite' areas. A localizing probe on a space molding was found an effective diagnostic tool. Using this probe, stereotopic localization of a foreign body may be associated with roentgen negative intraorbital structures, i.e. vessels, nerves, muscles. Topographic location of a foreign body helped explain a considerable vision acuity reduction in relatively transparent media, recurrences of hemorrhages to the fundus oculi, and the type of the pain syndrome. Foreign body removal is indicated in stubborn persistent pain and regressive time course of changes. PMID- 2264221 TI - [Examination of the optic nerve state in children with orbital injuries]. AB - The results of comprehensive examinations of 13 children with orbital injuries, in whom injuries to the optic nerve were diagnosed, are analyzed. Computer-aided tomography and examinations with visual evoked potentials helped detect the signs of optic nerve injuries in the first days after the injury even in cases without ophthalmoscopic changes. Grave disorders of the involved eye visual evoked potentials were detected, that evidenced organic changes of the third neurone, despite high vision acuity. Disordered visual evoked potentials of the intact eye as against age-specific norm were detected in 8 children. PMID- 2264222 TI - [Mathematical method of predicting possibilities of the development of suppurative complications in patients with perforating injuries of the eye]. AB - An image-recognition mathematical method was used to predict the development of purulent complications in 153 patients with perforating injuries to the eye. The results were processed by CM-4 computer. A method of the automated system 'training' is described and the results of examinations of the test group are presented. The suggested mathematical method, whose sensitivity index is 95 percent, provides recognition of expected purulent inflammation with a specificity of 78 percent. PMID- 2264223 TI - [Tolerant and intolerant intraocular pressure in glaucoma]. PMID- 2264224 TI - [Use of contact lenses in progressive myopia]. AB - Effects of contact lenses on clinical refraction and vision function were examined in patients with progressive myopia. A total of 535 patients were examined; contact lens correction was employed in 385 of these, 150 ones wearing spectacles have made up the reference group; the follow-up period was up to 5 years. Refraction remained unchanged by the end of the follow-up in 73.2 percent of patients using contact lenses, whereas in the reference group this value has made up 10.8 percent. The stabilizing action of contact lenses is explained mainly by improved function of the accommodation system of the eye, weakened in progressive myopia, and by improved quality of the retinal image. PMID- 2264225 TI - [Theoretical and clinical aspects of ocular hemodynamics examination using ophthalmo-sphygmography and rheo-ophthalmography]. AB - Correlation between the findings of ophthalmosphygmography and rheoophthalmography in patients with various levels of intraocular pressure is analyzed. Rheoophthalmography was found more informative in studies of the hemodynamics in glaucoma patients. Ophthalmosphygmography yields information on ocular vessels tone. Examination of ocular hemodynamics both the methods appears to be optimal, for these techniques supplement each other. PMID- 2264227 TI - [Comparative study of reproduction and Scheimpflug's photography of the crystalline lens]. AB - Two types of lens photography are compared in the same patients: photography according to Schaimpfluger and reproduction biomicrophotography with subsequent densitometry of the negatives. The authors find Schaimpfluger's photography preferable, its advantages consisting in convenience of the procedure and possibility to make standard pictures. An experienced worker can make high quality images of the lens optic section with a slit photographic lamp, this permitting an objective assessment of changes in the optic densities of different lenticular laminae. PMID- 2264226 TI - [Changes in the bulbar conjunctiva in essential hypertension and symptomatic arterial hypertension]. PMID- 2264228 TI - [State of the vitreous body in children with congenital uveitis]. AB - Comprehensive examinations of 150 children (229 eyes) with congenital uveitis have revealed vitreous changes in 75.9 percent. The structure of different opacities is presented and relationship between vitreous opacities patterns and subatrophy severity and intraocular pressure parameters detected. Recommendations are given on how to interpret the data of ultrasonic scanning and define the indications for opticoreconstructive surgery. PMID- 2264230 TI - [A case of penetration into the eye and orbit of a giant foreign body (a coil spring)]. AB - Descriptions of penetration of large foreign bodies into the orbit are rare. The authors describe a patient who got a coil spring, 40 cm x 2.5 mm in size, in the orbit, when collecting metal scrap; the spring slipped off and penetrated into the orbit. Before examination the exterior part of the spring at the orbital edge was cut off with cutting pliers. Ultrasonic scanning was used before and during surgery, that permitted visual monitoring of the operation and helped prevent possible complications when removing the fragment, thus helping a successful outcome of surgery. PMID- 2264229 TI - [Eye injuries in water transport]. AB - The author analyzes occupational and medicosocial aspects of ocular traumatism in the Northern basin water transport over 13 years. Wounds, foreign bodies, contusions, and burns predominated in the structure of injuries. Groups at high risk for eye injuries were distinguished with consideration for the subject's occupation, age, length of service, and type of work done. The author emphasizes the role of early urgent aid in favorable outcomes of injuries to the eye. PMID- 2264231 TI - [A rational method of cosmetic eye prosthesis]. AB - Effective cosmetic rehabilitation of patients with anophthalmia can be activated if methods based on the use of the cosmetic parameters for prostheses, listed below, are employed: (1) eyelid position and relief, (2) eye opening, (3) position of the iris and pupil, (4) diameters of the iris and pupil, (5) position and decline of the prosthesis, (6) depth of the prosthesis position in the orbit, (7) cavity filling with the prosthesis, (8) prosthesis mobility, (9) sclera color, (10) iris color. These prosthetic cosmetic parameters are of paramount importance for effective cosmetic rehabilitation of anophthalmia patients. PMID- 2264232 TI - [Effectiveness of magnetotherapy in optic nerve atrophy. A preliminary study]. AB - Magnetotherapy effects on visual functions (vision acuity and field), on retinal bioelectric activity, on conductive vision system, and on intraocular circulation were studied in 88 patients (160 eyes) with optic nerve atrophy. A Soviet Polyus 1 low-frequency magnetotherapy apparatus was employed with magnetic induction of about 10 mT, exposure 7-10 min, 10-15 sessions per course. Vision acuity of patients with its low (below 0.04 diopters) values improved in 50 percent of cases. The number of patients with vision acuity of 0.2 diopters has increased from 46 before treatment to 75. Magnetotherapy improved ocular hemodynamics in patients with optic nerve atrophy, it reduced the time of stimulation conduction along the vision routes and stimulated the retinal ganglia cells. The maximal effect was achieved after 10 magnetotherapy sessions. A repeated course carried out in 6-8 months promoted a stabilization of the process. PMID- 2264233 TI - [Eye manifestations of AIDS in the population of the Republic of Burundi]. PMID- 2264234 TI - [Retrospective analysis of the parameters of ocular hemodynamics in patients with initial open-angle glaucoma]. AB - The authors analyze ocular hemodynamics parameters in patients with ocular hypertension who were transferred to glaucoma group during ten-year follow-up. The patients who were transferred to this group were those whose hemodynamic parameters were lower than in the reference group. By the end of the follow-up period a negligible reduction of the hemodynamic parameters was observed in the 'hypertension' group and a statistically significant reduction in glaucoma patients. This lead the authors to a conclusion on the necessity of early prescription of drugs stimulating disordered ocular hemodynamics. PMID- 2264235 TI - [A clinical case. A case of bilateral retinal detachment after scleroplasty]. AB - After prophylactic scleroplasty for high complicated myopia the patient developed bilateral detachment of the retina. Therapeutic strategy with this patient is followed up. The described clinical case evidences the necessity of a strict validation of the choice of this or that surgical modality, particularly in cases when it concerns the only eye with vision. PMID- 2264237 TI - [Cyst of the optic disk]. PMID- 2264238 TI - [Injury of the cornea by a bee sting complicated by Pseudomonas aeruginosa and herpesvirus infections]. PMID- 2264236 TI - [Hydrops of the lacrimal sac complicated by the development of phlegmon]. PMID- 2264239 TI - [Debatable questions of aphakia correction after early surgery of congenital cataracts]. PMID- 2264241 TI - Pregnant women advised to avoid eating liver. PMID- 2264240 TI - [Allergic diseases of the eyes in children and adults (review of the literature)]. PMID- 2264242 TI - Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros) AB - Clinical, pathological and epidemiological details of scrapie-like encephalopathies are described in an arabian oryx and a greater kudu. Clinical signs included ataxia and loss of condition with a short, progressive clinical course (22 and three days, respectively). Histopathological examination of the brains revealed spongiform encephalopathy characteristic of that observed in scrapie and bovine spongiform encephalopathy (BSE). It seems probable that these cases have a common aetiology with BSE. Scrapie-like spongiform encephalopathies have now been described in five species of exotic artiodactyls in Britain indicating a, hitherto inapparent, wider range of ruminant species as natural hosts for these diseases. PMID- 2264243 TI - A vertically transmitted cystic renal dysplasia of lambs. AB - A new form of bilateral renal dysplasia in lambs appeared in a commercial sheep flock in 1982. The nature of the problem, the field investigations and the laboratory examinations carried out over three lambing seasons are described. It was concluded that the condition was vertically transmitted and genetic in origin. During the two years that accurate records were kept approximately 30 per cent of the suspected ram's progeny died with lesions of renal dysplasia. The condition recurred during a breeding trial in progeny from one of the two commercial rams originally used on the farm. An autosomal dominant mode of inheritance is suggested. The incidence illustrates the importance of keeping breeding records, especially when several rams are maintained in a flock, and the value of examining a large number of lambs post mortem. PMID- 2264244 TI - Comparison of the clinical utility of medetomidine/ketamine and xylazine/ketamine combinations for the ovariectomy of cats. AB - A controlled trial was conducted to assess suitability of combinations of medetomidine and ketamine for the ovariectomy of cats, to investigate the possible side effects, and to compare medetomidine/ketamine with a combination of xylazine and ketamine. Three hundred and thirty-seven cats were submitted to surgery; 100 were anaesthetised with 80 micrograms/kg medetomidine and 5 mg/kg ketamine, 137 with 80 micrograms/kg medetomidine and 7.5 mg/kg ketamine, and 100 were anaesthetised with 1 mg/kg xylazine and 10 mg/kg ketamine. The combinations were injected intramuscularly in the same syringe. The anaesthesia provided by the medetomidine/ketamine combinations was characterised by good muscle relaxation, good analgesia and minimal side effects. The only difference between the two doses of ketamine was the length of the period of anaesthesia. The advantages of the medetomidine/ketamine combination in comparison with xylazine/ketamine were the need for a lower dose of ketamine, a longer duration of action and better analgesia. Similar side effects were observed with both medetomidine/ketamine and xylazine/ketamine combinations. PMID- 2264245 TI - Observations on parasitic gastroenteritis and parasitic bronchitis in calves over two grazing seasons. AB - Two outbreaks of parasitic gastroenteritis were observed in a group of 10 first season grazing calves, one in mid-July and one in mid-September. In both cases emergency anthelmintic treatment was needed to prevent further damage. Severe clinical signs were observed together with high faecal egg counts and high serum pepsinogen and gastrin concentrations. Low total protein and albumin concentrations were also observed, especially during the second outbreak. The ostertagia antibody levels followed a similar pattern to the serum pepsinogen and gastrin concentrations. At the end of the housing period a mild type II ostertagiasis was observed. In the second grazing season the heifers did not show any signs of parasitic gastroenteritis, but there was a serious outbreak of husk which required treatment. PMID- 2264246 TI - Nucleotide sequence analysis of phocine distemper virus reveals its distinctness from canine distemper virus. PMID- 2264247 TI - Clostridium perfringens enterotoxaemia in two young horses. PMID- 2264248 TI - Vitamin A. PMID- 2264249 TI - Cooperation within Europe. PMID- 2264250 TI - Meat hygiene. PMID- 2264251 TI - Beechmast poisoning in ponies. PMID- 2264252 TI - Lyme disease in dogs and cats. PMID- 2264253 TI - Downer cow slaughter. PMID- 2264254 TI - Experiments on BSE. PMID- 2264255 TI - Normal kid cotwinned with an anasarcous fetus. PMID- 2264256 TI - Urinary incontinence in the bitch. PMID- 2264257 TI - Alterations in in vitro functional activities of alveolar macrophages exposed in vivo to mineral dusts. AB - To determine whether macrophages exposed to mineral dusts are altered, rats were exposed intratracheally to one of several mineral dusts, held 8 days, their lungs washed and the cellular composition of the fluid characterized morphologically and functionally. The number of cells recovered from lung washings of exposed rats increased 2 to 5 times relative to control rats; however, the percentage of such cells that were macrophages, or were capable of phagocytosis, adherence to glass or metabolism of carbohydrates via the hexose monophosphate shunt as indicated by reduction of nitroblue tetrazolium, were reduced. Silica dust produced the greatest effect, corresponding qualitatively to earlier in vivo studies. PMID- 2264258 TI - Ivermectin toxicology in a rhesus macaque. PMID- 2264259 TI - Fluoride pharmacokinetics in the ewe: a linear pharmacokinetics model. AB - The kinetics of fluoride was studied in a group of 3 adult ewes given sodium fluoride solutions at 3 dose levels (0.15, 0.375 and 0.75 mg/kg bw). Data were analysed using both compartmental and noncompartmental approaches. A 3 compartment open model was selected to describe the data. Comparison of the different parameters indicated an absence of change with dose level, suggesting that fluoride behaved linearly at the doses under study. The half-life of elimination was 2.57 +/- 1.28 h, the steady-state volume of distribution was 0.26 +/- 0.5 L/kg and the body clearance was 0.105 +/- 0.26 L/kg/h. It was concluded that a single intravascular fluoride administration (bolus) may be used to evaluate oral bioavailability of fluoride in sheep in toxicity studies. PMID- 2264260 TI - Toxicity of Abrus precatorius in Nubian goats. AB - Eight Nubian goats were given Abrus precatorius seed at 2, 1 and 0.5 g/kg/day by stomach tube. Six goats receiving the plant seed at 2 and 1 g/kg died between days 2 and 5. One goat receiving Abrus seed at 0.5 g/kg/day died on day 32 and the other animal in the group was killed on day 33. The main signs of Abrus poisoning were inappetence, bloody diarrhea, dyspnea, dehydration, loss of condition and recumbency. The lesions were fatty change and necrosis of hepatocytes and renal convoluted tubules, pulmonary hemorrhage, edema and emphysema, and erosions of the abomasal and intestinal epithelium. These changes were accompanied by increases in GOT and gamma GT activities and urea, creatinine, sodium and potassium and by decreases in total protein and albumin in the serum of Abrus-poisoned goats. The blood cell changes indicated hemoconcentration. PMID- 2264261 TI - Evaluation of the maternal and developmental toxicity of aluminum from high doses of aluminum hydroxide in rats. AB - The potential of aluminum hydroxide [Al (OH)3] to induce developmental toxicity in rats was evaluated in the present study. Al (OH)3 was given by gavage at dose levels of 192, 384, and 768 mg/kg/day to groups of pregnant rats from day 6 through day 15 of gestation. Control animals received distilled water. Pregnant rats were evaluated for body weight, weight gain, food consumption, appearance, behavior and reproduction data. Cesarean sections were performed on gestation day 20, and the fetuses were removed for teratological evaluation. No significant maternal or developmental toxicity was observed at any Al (OH)3 dose level. Consequently, the no-observed-effect level (NOEL) for Al(OH)3 maternal or developmental toxicity would be greater than or equal to 768 mg/kg/day, which was the highest dose tested. This dose would be equivalent to a 60 kg person ingesting 16 g Al/day. PMID- 2264262 TI - Diagnostic use of blood porphyrin and radiographic changes in lead exposure in goats. AB - Blood porphyrin, hematological examination and radiographic changes were evaluated for the detection of lead intoxication in goats given daily po doses of 10, 15 and 20 mg lead acetate (5.43, 8.15 and 10.86 mg lead)/kg body weight for 30, 30 and 31 days, or a total of 91 days. Blood porphyrin was found a sensitive indicator with direct correlation (r = 0.976) to blood lead concentration. Basophilic stippling was not seen in the lead-exposed goats. Radiopaque bands developed at the distal metaphysis of the radius in 7 of the 12 lead-exposed goats at day 30. The usefulness of this sign for the diagnosis of lead exposure in goats requires further investigation. PMID- 2264263 TI - Effect of Astragalus lusitanicus lam in experimental subchronic neurotoxicity of lambs. AB - A study was made of effect produced in lambs by the administration of Astragalus lusitanicus Lam at a daily dose of 1.25 g dry plant/kg live weight for 28 d. Clinical effects were not seen. No significant modifications were found in hematocrit, red or white blood cell count, differential leukocyte count, hemoglobin, methemoglobin, thiamine, lactate or pyruvate. Significant changes affected plasma LDH, GOT and CPK activity, where a progressive increase (70% for GOT and 113% for CPK) suggested changes in the CNS subsequently confirmed by histological examination (degeneration of neurons in the cerebrocortical grey matter, degeneration and loss of Purkinje cells in the cerebellum, satellitosis, neuronophagia, hyperemia and small hemorrhages throughout the CNS). Thiamine deficiency may play a role in this type of poisoning. PMID- 2264264 TI - Chronic hepato-toxicity of Senecio erraticus in calves from two 50-day feeding periods in consecutive years. AB - One-year-old male Holstein Fresian calves were fed low doses of Senecio erraticus during two 50-d periods in consecutive years to determine its chronic effect on the liver. Toxic liver effects were determined by monitoring serum levels of hepatic enzymes, bromosulphthalein retention (BSP), and histopathological changes in the liver at times before, during and after Senecio ingestion. A gradual increase in BSP retention was observed at days 60 and 90 during the first feeding period. Histological studies of the liver showed hepatocellular megalocytosis and karyomegaly, and hypertrophy of Kupffer cells in both groups. Periportal fibrosis, bile duct proliferation and the presence of periportal hyperchromatic and hypertrophic hepatocytes was seen after the second feeding period. PMID- 2264265 TI - The toxicity of yellow oleander (Thevetia neriifolia juss) seed kernels to rats. AB - Toxic effects of yellow oleander (Thevetia neriifolia Juss) seed kernels were evaluated against the roof rat (Rattus rattus Linn). Crushed ground seed kernels were fed with bait at 20 and 30% concentrations. The bait was fed up to mortality or for a maximum of 10 d. Major signs of poisoning observed were hind limb paralysis, rolling of the body on the long axis, circular flailing of the tail, muscular twitch, tetanic convulsions, tremors, collapse and death. Significant reductions in the rats' weights were observed. The observed mortalities were 16/20 and 18/20 with the above respective doses. Statistically significant reductions in hemoglobin, red blood cell count, total leucocyte count and neutrophils, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased BUN, SGOT and LDH, were also significant. Histopathological studies showed inflammatory and degenerative changes in the liver and kidney. Severe to moderate fatty metamorphosis, congestion, hepatocytolysis, nuclear degeneration, pyknosis, and necrosis were major changes in the liver. Proliferation of glomerular endothelium, hypercellularity of the glomerulus, necrosis of convoluted tubular epithelium, disappearance of nuclei and pyknosis were important changes in the kidney cortical region. Atrophy, erosion and inflammatory changes were observed in the stomach mucosal linings. PMID- 2264266 TI - Rapid screening and spot tests for the presence of common poisons. PMID- 2264268 TI - Vitamin E is non-toxic to goats. PMID- 2264267 TI - The adsorption of quinine and quinidine to activated charcoal with and without magnesium sulfate. AB - The effect of magnesium sulfate on the in vitro adsorption of quinine and quinidine to activated charcoal (AC) was studied. Solutions of quinine and quinidine were prepared at concentrations of 5 and 10 micrograms/ml and at simulated toxic concentrations of 62.5, 125 and 250 micrograms/ml in distilled water. Drug-charcoal slurries were vortex mixed, centrifuged and analysed for free drug in the supernatant. Quinine had adsorption capacities of 78.2 to 100% with 12.5 or 50 mg AC; 12.5 or 50 mg AC adsorbed 29.5-87.2% of the quinidine. Quinine (250 micrograms/ml) had adsorption capacities of 0.0, 21.1, 52.4, 78.3 or 93.8% to 12.5, 50, 125, 250 or 500 mg AC, respectively. There was a corresponding increase quinine and quinidine adsorption at increasing concentrations of AC. The adsorption of quinine and quinidine seemed dose dependent. Magnesium sulfate (7.5 mg/ml) enhanced the adsorption of quinine to AC, but increased the amount of AC required for quinidine-charcoal adsorption. PMID- 2264269 TI - Nicotine poisoning in a dog. AB - Nicotine poisoning is a rarely reported toxicosis. The clinical signs and symptoms are complex and are mostly of central nervous system derangement. In addition, animals may have hypersalivation, vomiting, diarrhea, tachycardia, tachypnea, hypertension and hyperthermia. Some animals are presented in total collapse with slow and shallow respirations, hypotension, dilated pupils, and a weak, rapid and irregular pulse. Treatment is directed toward removing the unabsorbed poison and diluting, and counteracting or controlling the animal's signs. This report emphasises the comparative ease with which a dog would readily ingest chewing tobacco, which is sweet in taste, and come down with nicotine poisoning, as compared to cigarette tobacco which is nonpalatable and therefore less of a threat. The report further discusses clinical nicotine toxicosis, its incidence, clinical manifestations, diagnosis, prognosis and treatment. PMID- 2264270 TI - A case of Datisca glomerata poisoning in beef cattle. AB - Six of 175 Angus heifers died after ingesting excessive amounts of Durango root (Datisca glomerata). Animals had rumens full of Durango root, were extremely lethargic, and had diarrhea prior to death. The animals had nonspecific postmortem lesions. This case is discussed in light of previous findings from trials in which Durango root was experimentally fed to cattle. PMID- 2264271 TI - The influence of repeated oral administration of dichlorvos on circulating esterases in buffalo calves (Bubalus bubalis). AB - Alterations in circulating esterases induced by dichlorvos and their reversibility were investigated in male buffalo calves. Changes in blood glucose and total plasma proteins were also monitored. Animals received 4 or 8 mg dichlorvos/kg/day po for 28 consecutive d. Dichlorvos caused dose- and time- dependent significant (P less than 0.01) inactivation of blood esterases. Maximal inhibition of plasma cholinesterase (87-94%) and serum carboxylesterase (51-67%) was observed on the 28th day. An increase in blood glucose and total plasma proteins occurred during the dosing period; these parameters returned to control values in surviving animals within 7 d after the final dose. Activities of esterases returned to 45-70% of normal the 14th d after cessation of dichlorvos dosing. PMID- 2264272 TI - Poisoning with plants and mushrooms in Sri Lanka: a retrospective hospital based study. AB - A retrospective hospital-based study in Sri Lanka showed that out of 4556 cases of poisoning, 2.5% were caused by plants and mushrooms. Gloriosa superba (44%), and Ricinus communis (24%) were the commonest plants responsible for poisoning; 39% of the victims were less than 15 y old. Gastric lavage and iv fluids were the most common therapeutic measures used. There were 8 deaths, all due to G superba. There is a need for public education to prevent poisoning, which is a major health concern. PMID- 2264273 TI - Sorghum cystitis ataxia syndrome in horses. PMID- 2264274 TI - 'Unrepentant' dealer sentenced for fraudulent animal drugs. PMID- 2264275 TI - A possible relationship between climate, vegetation, management and occurrence of hard yellow liver disease. PMID- 2264276 TI - Partial versus complete attenuation of single portosystemic shunts. AB - Twenty-two dogs with congenital single portosystemic shunts were treated by partial or complete ligation of the shunts. Intraoperative portal pressures before and after shunt ligation, and central venous pressures measured after 3 minutes of temporary shunt occlusion, were evaluated prospectively. Portal pressures after ligation, increases in portal pressure above baseline values, and decreases in central venous pressure during temporary occlusion were significantly greater in dogs that underwent partial portosystemic shunt ligation and in dogs that developed postoperative complications. Absence of arborizing intrahepatic vasculature in intraoperative mesenteric portograms did not indicate whether partial or complete shunt attenuation could be performed safely, but it was correlated with greater occurrence of post-operative complications. PMID- 2264277 TI - Status epilepticus after ligation of portosystemic shunts. AB - Status epilepticus developed in four dogs, 2 to 3 days after ligation of an extrahepatic portosystemic shunt. Pentobarbital or phenobarbital intravenously was required to control seizure activity. Two dogs treated with phenobarbital recovered. Exacerbation of hepatic encephalopathy secondary to metabolic changes after surgery may be a cause of this syndrome. A treatment protocol for status epilepticus after ligation of a portosystemic shunt is proposed. PMID- 2264279 TI - Treatment of trochanteric ulcers with cranial sartorius and rectus femoris muscle flaps. AB - Five dogs with pressure ulcers over the greater trochanter were treated by debridement and transposition of the cranial part of the sartorius or the rectus femoris muscle. Both muscles had vascular anatomy that allowed transposition based on a major vascular pedicle. All wounds healed promptly by primary intention and no ulcer recurred. The cranial sartorius flap technique was easier to perform than the rectus femoris technique. PMID- 2264278 TI - Excision of tumors in the nasal vestibule of two dogs. AB - Two dogs with tumors in the left nasal vestibule were treated by surgical excision of the affected part of the nose. Radiation and chemopotentiation were used in one dog, which remained tumor-free after 12 months. When recovering from anesthesia, the second dog developed respiratory distress associated with upper airway obstruction and failure to mouth breathe. The dog was successfully treated by temporary tracheostomy and remained tumor-free after 3 months. Surgery preserved the function of the right nostril and gave an acceptable cosmetic result in both cases. PMID- 2264280 TI - Talocalcaneal luxation: An anatomic and clinical study. AB - Talocalcaneal luxation in dogs was studied by anatomic dissection of the talocalcaneal joint in cadavers and review of five clinical cases. The integrity of the talocalcaneal joint was maintained by two strong ligaments traversing the tarsal sinus between the two bones. The joint was found to be a low motion joint. Luxation in clinical cases was not always apparent on standard radiographic views. Three dogs were treated surgically with a screw inserted in lag fashion from talus to calcaneus. One luxation was treated surgically with figure-of-eight orthopedic wires and one was treated with external coaptation. Four dogs returned to their previous levels of function without clinically detectable lameness. PMID- 2264282 TI - Ellis pin complications in seven dogs. AB - Complications developed with the clinical use of Ellis pins in external skeletal fixation in seven dogs weighing 11 to 24 kg. Pins broke at the threaded nonthreaded shaft junction in six dogs, and there was radiographic evidence of pin loosening six dogs. One pin pulled out causing loss of fixation in one dog. These complications with the recently introduced Ellis pin emphasize a need for further evaluation of its proper use. PMID- 2264281 TI - Osteochondrosis of the lateral trochlear ridge of the talus in seven Rottweiler dogs. AB - Eleven lesions of osteochondrosis in the lateral trochlear ridge of the talus were diagnosed in seven young Rottweiler dogs. Diagnosis was based on clinical and radiographic evaluations. Defects in the lateral trochlear ridge and osteochondral fragments arising from the dorsal and proximal margins of the ridge were visible radiographically. The dorsal 45 degrees lateral-plantaromedial oblique (D45 degrees L-P1MO) projection was the most useful in identifying the lesions. Exploratory arthrotomies were performed in six affected tarsi. In three cases, histologic examination revealed mineralized osteochondral fragments consistent with a diagnosis of osteochondrosis. PMID- 2264283 TI - Vascular injury associated with naturally occurring strangulating obstructions of the equine large colon. AB - Ten horses were euthanatized before, during, or after surgery to correct severe volvulus of the large colon. At surgery, the colonic serosa changed from blue gray, blue or purple toward a more normal pink in seven horses after the volvulus was corrected. The mucosa consistently remained black or dark red. Results of postmortem colonic microangiography revealed perfusion of the serosa and the circular and longitudinal muscle layers, but mucosal perfusion was limited by thrombosis in the muscularis mucosae and submucosa. There was evidence of thrombosis of the mesenteric colic vessels in six horses. Damage to the colonic vascular system, especially thromboembolism in the submucosa, may be an important limitation to colonic viability after surgical correction of volvulus of the large colon. PMID- 2264284 TI - Laryngeal hemiplegia in draft horses. A review of 27 cases. AB - Case records of 27 draft horses with laryngeal hemiplegia were reviewed. Twenty one horses were treated by ventriculectomy with or without prosthetic laryngoplasty, and 17 owners were contacted to determine the results. Fifteen horses improved after surgery and were able to perform to the owners' expectations. Performance improved significantly and hospitalization was shorter after ventriculectomy alone. Results of this study indicate that the clinical signs of exercise intolerance and excessive inspiratory noise associated with left laryngeal hemiplegia in draft horses can be treated successfully by ventriculectomy without prosthetic laryngoplasty. PMID- 2264285 TI - Immunological aspects of mammary tumors in dogs and cats: a survey including own studies and pertinent literature. AB - Naturally occurring cancer in companion animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals. In dogs and cats, as in man, a role for immune responses is indicated in the development of tumors. A survey is presented based on the literature and our own studies concerning the immunological and immunotherapeutic aspects of canine and feline mammary neoplasia. In dogs bearing mammary neoplasms, circulating immune complexes appear to play a negative role in the generation of effective antitumor immune responses. The functional role of peripheral blood lymphocytes and tumor infiltrating lymphocytes in dogs and cats with mammary tumors is not yet fully established. No tumor antigen responsible for humoral or cellular responses has yet been identified. Extracorporeal perfusion of serum of dogs with mammary tumors and subcutaneous administration of mitomycin- and neuraminidase-treated autologous tumor cells are associated with improved prognosis. The opposite was true for i.v. treatment with BCG or Corynebacterium parvum vaccine in our study, in contrast to a previous report. A number of other treatment modalities in cats and dogs with mammary carcinomas failed to induce tumor regression. Canine and feline mammary carcinomas are good candidates for modern immunotherapeutic approaches. PMID- 2264286 TI - Blastogenic responses and production of TCGF by mononuclear cells isolated from the bovine endometrium. AB - Mononuclear cells (MNCs) were isolated from the endometrium of cattle by enzymatic digestion followed by centrifugation on a density gradient. Of the cells isolated, 32 +/- 3.2% rosetted AET-treated sheep red blood cells, 9 +/- 0.4% possessed surface membrane immunoglobulin, and 15 +/- 6.1% were esterase positive. The cells possessed the ability to proliferate in the presence of T cell mitogens and produced T cell growth factor (TCGF) after in vitro stimulation with Concanavalin A. Endometrial MNCs did not appear to suppress the blastogenesis of peripheral blood MNCs. PMID- 2264287 TI - Characterization of heteromyeloma fusion partners which promote the outgrowth of porcine hybridomas. AB - Production of porcine monoclonal antibodies for use in research and immunotherapy has been hampered by the lack of suitable fusion partners which promote high efficiencies of hybridoma out-growth and immunoglobulin synthesis. To overcome these obstacles, five heteromyeloma fusion partners (HM-1,2,3,4 and 5) were constructed by successively fusing porcine lymphocytes with murine myeloma cells or murine x bovine heteromyeloma cells. Following section of hypoxanthine/aminopterin/thymidine (HAT)-sensitive mutants, karyotypes, growth rates and surface phenotypes of the heteromyelomas were determined. Karyotyping revealed an increase in the mean number of chromosomes present in HM-1,4 and 5 cells. Peak doubling times of the parental and HM cells ranged between 12.2 and 17.4 h. Uisng flow microfluorimetry and monoclonal antibodies specific for class I/II major histocompatability antigens, it was determined that the surface phenotype of HM-1,2,3,4 and 5 resembled that of the parental murine X63 myeloma cells. HM 1,2,3,4 and 5 were evaluated for their abilities to serve as fusion partners. Highest percentages of hybrid outgrowth (37%) and immunoglobulin synthesis (52%) were observed when HM-1 was fused with procine lymphocytes. When cloned, percentage of outgrowth and immunoglobulin synthesis increased if HM-1 and HM-2 were used as fusion partners. Cryopreservation of HM-1 and HM-2 did not adversely affect their abilities to promote hybrid outgrowth or immunoglobulin synthesis. During the first week following fusion of porcine lymphocytes with heteromyelomas, murine thymocytes were found to be essential for survival of the nascent hybrids. To confirm that immunoglobulin secreted by hybridomas was of porcine and not murine or bovine origin, culture supernates were subjected to SDS gel electrophoresis, electroblotted and identified. using species-specific isotyping reagents. Two of four cell lines tested secreted porcine light chains and one of four cell lines secreted whole IgM molecules. This paper is the first to describe porcine heteromyelomas for use as fusion partners. Similar to findings of human and bovine studies, our data suggest that heteromyeloma fusion partners perform better than rodent myelomas for creating hybridomas synthesizing porcine immunoglobulin. PMID- 2264288 TI - The effect of the endophyte (Acremonium coenophialum) and associated toxin(s) of tall fescue on serum titer response to immunization and spleen cell flow cytometry analysis and response to mitogens. AB - Experiments were conducted with rats and mice to evaluate the effect of the consumption of endophyte (Acremonium coenophialum) and associated toxin(s) infected tall fescue on humoral and cellular aspects of immune function. Treatment diets were: (1) rodent chow (RC) or (2) rodent chow mixed 1:1 (w/w) with endophyte infected (E+) or (3) non-infected (E-) tall fescue seed. Rats fed the E+ diet in experiment 1 (43 days) exhibited a lower (P less than 0.05) serum titer to sheep red blood cell (SRBC) immunization than those fed the E- diet (38.4 vs 131.3). The E+ rats also had lower (P less than 0.01) white cell counts than either RC or E- groups (5225 vs 8959 and 7491/mm3). Spleen cells from mice fed the E+ diet for 37 days exhibited a reduced (P less than 0.05) response to the mitogens Concanavalin A and lipopolysaccharide. Flow cytometric analysis revealed a significant (P less than 0.01) 42% increase in T suppressor cell numbers in spleens of mice fed the E+ vs RC diets. PMID- 2264289 TI - [The organization of medical care in large-scale industrial accidents]. PMID- 2264290 TI - [The forensic medical personal identification of the victims in catastrophes and natural disasters]. PMID- 2264291 TI - [A new approach to resolving the problem of rendering medical care in mass casualties]. PMID- 2264292 TI - [The place of extracorporeal detoxication methods in disaster medicine]. PMID- 2264293 TI - [Mass thermal injuries: care from American military physicians for the victims in the railroad catastrophe in Bashkiria]. PMID- 2264294 TI - [Eye injuries in catastrophes and the principles of rendering medical care at the evacuation stages]. PMID- 2264296 TI - [The methodology for studying and predicting the sociomedical problems of the consequences of war]. PMID- 2264295 TI - [Posttraumatic stress disorders in children and their mental rehabilitation]. PMID- 2264297 TI - [The planning of measures to eliminate the sequelae of catastrophes]. PMID- 2264299 TI - [The moral responsibility and spiritual culture of the physician]. PMID- 2264298 TI - [The place and role of mobile field hospitals in the system of the general national defense of Yugoslavia]. PMID- 2264300 TI - [Medical support for the Soviet troops in the Manchurian Strategic Offensive Operation (August 9-September 2, 1945)]. PMID- 2264301 TI - [Earthquake readiness]. PMID- 2264302 TI - [The Party organization of the Main Military Medical Command of the Red Army in the first period of World War II (June 1941-November 1942)]. PMID- 2264303 TI - [The characteristics of the pathogenesis, clinical picture, diagnosis and treatment of explosive mine injuries]. PMID- 2264304 TI - [Rare variants of the vertebrosubclavian "steal" syndrome]. PMID- 2264305 TI - [The immunological reactivity of patients with acute odontogenic inflammatory diseases]. PMID- 2264306 TI - [The surgical treatment of Dupuytren's disease]. PMID- 2264307 TI - [The iridodiagnostic study of hereditary signs]. PMID- 2264308 TI - [The immediate results of treating a gunshot femoral fracture by using damped external transosseous osteosynthesis]. PMID- 2264309 TI - [An improvement in the lathe for crimping the caps on drug bottles]. PMID- 2264310 TI - [A set of elevators for the endonasal repositioning of bones]. PMID- 2264311 TI - [An attachment for local hypothermia with liquid nitrogen]. PMID- 2264313 TI - [The 50th anniversary of the founding of the Military Naval Medical Academy]. PMID- 2264314 TI - [The organization of universal compulsory legal education in a military unit or institution]. PMID- 2264312 TI - [Fedor Fedorovich Andreev (on the 90th anniversary of his birth)]. PMID- 2264315 TI - [Military physicians of the Bundeswehr in the USSR]. PMID- 2264316 TI - Platelet concentrates in an additive solution prepared from pooled buffy coats. 1. In vitro studies. AB - A new method for the preparation of platelet concentrates (PCs) is described. The source material is buffy coat (BC), prepared after keeping standard CPD whole blood units at room temperature for 6-12 h, followed by centrifugation at 3,500 rpm for 10 min (first series) or 4,000 rpm for 12.5 min (second series). BC, separated from plasma and red cells, was kept at room temperature for a further 8 12 h without agitation. Pools of 6 (first series) and 4 (second series) BCs were prepared using a sterile docking device and suspended in a platelet-additive solution (PAS) containing sodium/potassium chloride, citrate, phosphate, and mannitol. After gentle centrifugation, the platelet-rich supernatant was expressed to and stored in one (first series) or two (second series) 1-liter polyolefine (PL-732) containers. In the first series, the total number of platelets was 316 +/- 59 x 10(9) per PC (yield 65%). However, when the method was applied at a routine scale, the yield varied considerably and was shown to be strongly dependent on the hematocrit of the BCs. A number of steps were taken to standardize the technique which resulted in an improved yield (77.3 +/- 8.7%) with 316 +/- 52 x 10(9) platelets (mean +/- SD, range 203-490, n = 134), obtained from 4 BC pools and lower leukocyte contamination than before, 18 +/- 17 X 10(6) per preparation (range 1-73, microscopic counting, n = 38). The storage medium consisted of a mixture of plasma and PAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264317 TI - Alternative fuels for platelet storage: a metabolic study. AB - We have studied the metabolism of platelets in vitro using washed platelets. Oxygen uptake and fuel utilization were measured. It was found that glucose is never oxidized to any significant extent and is always converted to lactate, regardless of oxygen availability. Oxidative metabolism fuels 70-100% of the ATP turnover, and oxygen uptake is the same whether the platelet is consuming glucose, acetate or only an unidentified endogenous fuel. When acetate is the added fuel, no endogenous fuel is oxidized, whereas the addition of glucose results in sparing of only 8% of endogenous fuel. Preliminary storage experiments using plasma-free media show that an acetate-containing buffered salt solution provided excellent storage conditions and that a medium without any exogenous fuel is better than one containing glucose. Thus we conclude that a successful storage medium should contain minimal amounts of glucose, and an oxidizable fuel such as acetate, in order to supplement the endogenous one. PMID- 2264318 TI - Flow-cytometric method for counting very low numbers of leukocytes in platelet products. AB - We provide a detailed description of a new method for counting very low numbers of leukocytes present in platelet products. The method uses fluorescent staining of leukocyte DNA using propidium iodide and flow cytometry. The assay is accurate over a range of leukocyte concentrations from 0.1 to 10 WBC/microliter. We validated the method using specially designed dilution studies and applied it to the measurement of leukocyte content in leukocyte-depleted platelet products prepared by apheresis or filtration. This method should prove useful in studies which address the clinical impact of leukocyte-depleted platelet products. PMID- 2264319 TI - Comparison of false-positive reactions in direct-binding anti-HIV ELISA using cell lysate or recombinant antigens. AB - In a 2-year study of false-positive anti-HIV-1 tests in blood donors at Manchester and Lancaster Blood Banks, the reactions associated with a HIV infected cell lysate antigen were compared with those using recombinant-antigen based tests. In year 1 (cell lysate test) at Manchester BTS 0.21% of 119.178 donations were repeatedly reactive, compared with 0.53% of 119,004 donations in year 2 (recombinant antigen). Reactive sera were tested at Manchester PHL by three different immunoassays. Referred specimens were classified as anti-HIV positive (95-100% reactive in all the assays), equivocal or negative (negative results in all three immunoassays). Two donors were confirmed to be anti-HIV positive over the 2-year period. Most sera were negative by confirmatory immunoassays in years 1 and 2. In year 1, a study of 60 referred sera with sex- and age-matched controls showed high correlation between a reactive anti-HIV-1 screening test and indeterminate anti-HIV-1 patterns on Western blot showing reactions with HIV gag-coded proteins. In year 2, less than 10% of referred sera were reactive by Western blot, and there was no correlation between a reactive screening anti-HIV test, the strength of signal in the test or a reactive Western blot. Follow-up showed that donors whose sera were reactive in years 1 and 2 by the anti-HIV-1 screening test formed almost two different populations. Four donors with equivocal anti-HIV-1 confirmatory tests had anti-HIV 'envelope' reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264320 TI - Severe intravascular haemolysis in a renal transplant recipient due to anti-B of donor origin. AB - A group B recipient of a group 0 kidney developed severe intravascular haemolysis due to the formation of anti-B. Immunoglobulin allotyping of donor serum, recipient serum and 'unexpected' anti-B antibody showed the antibody to be of donor origin. The patient and donor genotypes were Gm 3;5/3;5 and Gm 1,2;21/1;21, respectively, and the anti-B antibody allotype was Gm 1;21. The group B recipient of the other donor kidney showed no evidence of haemolysis. Possible factors influencing the occurrence and severity of post-transplantation haemolysis are discussed. The production of anti-A or anti-B antibodies in non-group 0 patients who receive group 0 organ transplants is well described [1-8]. We report a case of severe intravascular haemolysis in a group B patient who received a group 0 kidney, together with immunoglobulin allotyping studies which show conclusively that the antibody responsible for the haemolysis was of donor origin. PMID- 2264321 TI - Management of severe hemolytic disease with ultrasound-guided intravascular fetal transfusions. AB - Between January 1987 and March 1989, 22 fetuses with severe hemolytic disease were treated with 64 ultrasound-guided intrauterine intravascular transfusions. Eighteen infants survived and are doing well. In 12 fetuses, hydropic changes were present at the first transfusion; 9 of these survived. In 8 of the 10 fetuses with a gestational age less than 26 weeks, intrauterine treatment was successful. PMID- 2264322 TI - Evaluation of monoclonal antibodies with putative specificity for human IgG allotypes. AB - Fourteen monoclonal antibodies (MAbs) of putative specificity for human IgG allotypes and isoallotypes were evaluated for reactivity and specificity in 8 different assay systems. The study showed that the MAbs tested could be classified into 1 of 4 groups: those exhibiting allotypic specificity regardless of the assay system, allotypic specificity dependent on the assay system, isoallotypic specificity, and those showing neither allotypic nor isoallotypic specificity. These observations were presumably dependent on antigen presentation, epitope integrity and/or antibody multispecificity. For the G1m(a), G1m(f), G1m(z), G3m(g) and G3m(u) specificities, MAbs have been produced which can be used for routine typing purposes in defined haemagglutination and enzyme linked immunosorbent assay systems. MAbs are also available that show 'non-g' isoallotypic specificity. PMID- 2264323 TI - Autologous transfusion practice. PMID- 2264324 TI - A new cardiology service in Antigua and Barbuda. AB - Antigua, which occupies a central position in the north-eastern Caribbean, was the site of a new Cardiac Centre, based at the Government Hospital. Together with the smaller surrounding Islands, a population of a quarter of a million/persons was thus offered cardiac care with great savings in total cost and travelling. The new cardiac clinic enrolled 78 patients, and provided a base for surgery assessment, pacemaker follow-up, and teaching. A new echocardiography service benefited 127 patients, of whom 9 subsequently underwent open-heart surgery. Two new avenues for surgery were formed. A new permanent pacemaker implantation service resulted in 3 implants, and temporary pacemaker therapy became operational. These services ceased in late 1989. PMID- 2264325 TI - Diabetes mellitus and public health in Guadeloupe. AB - Diabetes mellitus is now among the ten leading causes of death in the Caribbean. Studies of the prevalence of dysglycaemic disorders and risk factors for diabetes are necessary in order to design and implement tailored prevention programmes. The present study is of a representative sample of the adult population in Guadeloupe. The estimated prevalence of diabetes is 5.8% in adults, and that of impaired glucose tolerance is 7.4%. The percentage of insulin-treated patients is low, 14% of diabetics. The principal risk factors of diabetes, as classically recognised, are shown to operate. At the individual level, the presence of a diabetic parent is a greater relative risk factor than obesity. However, considering the large percentage of persons who are obese, obesity seems to be the principal factor at which a primary prevention programme at the community level should be aimed, in order to limit the incidence of hyperglycaemic states. PMID- 2264326 TI - Insulin receptor studies of erythrocytes and mononuclear leucocytes in phasic insulin diabetes mellitus. AB - This study was designed to investigate any differences in cellular binding of insulin between phasic insulin-dependent (malnutrition-related) diabetes mellitus (PIDDM) and insulin-dependent, non-insulin-dependent, and normal controls. Isolated, washed red and white blood cells obtained after 12-14 hr fast, were separately incubated with varying concentrations of non-radioactive insulin, and a fixed quantity of radioactively labelled insulin. After the 3-hr incubation, cells were washed with buffer, and radioactivity determined on an autogamma counter. Percentage binding, receptor sites number and affinity were all determined by linear regression of the Scatchard plot. Fasting plasma insulin and glucose levels were also assayed. The results obtained show decreased binding of insulin in red blood cells [11.3 +/- 1.3%) and white blood cells 2.9 +/- 0.5%) in PIDDM. This was due to decreased receptor sites (red blood cells 39 +/- 11; white blood cells 0.5 +/- 0.11 x 10(4] as well as decreased affinity (red blood cells 0.14 +/- 0.03 x 10(9) M-1; white blood cells 0.17 +/- 0.04 x 10(9) M-1) when compared to the normal and diabetic (both insulin and non-insulin-dependent) controls. Phasic insulin-dependent diabetes (malnutrition-related diabetes mellitus) is characterized by decreased red and white cellular binding to insulin, in addition to decreased production of insulin. PMID- 2264327 TI - Comparison of plasma viscosity and fibrinogen concentration in African insulin dependent and non-insulin-dependent diabetics with and without hypertension. AB - Alterations in Relative Plasma Viscosity (RPV) and Plasma Fibrinogen Concentration (PFC) were compared in 24 insulin-dependent (IDDM) and 33 non insulin-dependent (NIDDM) black Nigerian diabetics, during the course of treatment. Both PFC and RPV were significantly (p less than 0.001) increased in the diabetics, as a group, compared to a non-diabetic control group. PFC and RPV showed consistently marginal, though insignificant, increases in the IDDM vs NIDDM. Hypertensive diabetics, as a group, had significantly greater PFC (p less than 0.025), and RPV (p less than 0.025) than normotensive diabetics. Although PFC was significantly (p less than 0.05) raised in hypertensive IDDM, there was no marked change in RPV, compared to normotensive IDDM. Neither PFC nor RPV revealed a significant change between hypertensive and normotensive NIDDM. The implication of the present findings is that insulin-dependent diabetics may be more prone than non-insulin-dependent diabetics to develop haemorheological and hence circulatory disorders. PMID- 2264328 TI - Assessment of community health aides. AB - A research project funded by the Commonwealth Caribbean Medical Research Council (CCMRC) began in February 1987, to study aspects of the situation in connection with 508 Community Health Aides (CHAs) employed in the Government Service of Jamaica. There were in the service 1,328 CHAs in 1978, reduced to 1,183 in 1982 and to 1,168 in 1984. By 1985/86 the numbers were further reduced, reaching the low figure of 508. This report deals specifically with the responses of 615 members of the community who were interviewed, and questionnaires were returned from all parishes in the four Administrative Health areas in Jamaica. The responses from community members are very important in the assessment of community health aides as members of the community health team. A number of useful and practical suggestions were reflected in their responses regarding service from community health aides. PMID- 2264329 TI - Life-stress events, depression and purpose-in-life in first-admission alcoholics and members of Alcoholics Anonymous. AB - The relationship between alcoholism, depression, life-stress events and purpose in-life is a very complex one. Thirty-five first admission alcoholics and an equal number of members of Alcoholics Anonymous were assessed, using objective measures of alcoholism, depression, stress and purpose-in-life. The results indicate that there were significant differences between the two groups on drinking behaviour, depression and purpose-in-life. No differences were found between the groups on the stress questionnaire. Positive correlations were found between drinking behaviour and depression, life events and purpose-in-life. PMID- 2264330 TI - Casualty transit time for 100 adult walk-in patients at the University Hospital of the West Indies. AB - The Casualty Department of the University Hospital of the West Indies (UHWI) has evolved in an ad hoc manner over the last decade, and questions regarding its appropriateness and effectiveness as an Emergency Department persist. This study of 100 systematically-selected patients attempts to assess time utilization during transit, as dictated by the present system of patient management. Time to first contact averaged 2 hr 38 min (158 min). The mean total time was 3 hr 46 min (226 min) and mean total waiting time was 3 hr 10 min (190 min), versus a mean total utilized time of 19 min. Actual contact time with casualty officers averaged only 8.3 min. Referrals to specialist services constituted 11% of the sample, and overall mean waiting time for specialists was 2 hr 16 min (136 min) with a mean contact time of 48 min. Given that the mean total time of 3 hr 46 min is not inordinately long in a public health system such as ours, the recommendation is being made for a modified coding and triage system to reduce time to first contact for more urgent cases. PMID- 2264331 TI - Prevalence of reactive serological tests for syphilis in the Jamaican population. AB - Serological tests for syphilis (STS) were performed on sera from 15,876 members of the general adult population, 3,039 pregnant women and 1,029 children, in order to assess the prevalence and value of reactive STS in Jamaicans; 2.7% of sera from the general adult population, 4.7% from pregnant women and 2.2% from children were reactive in the Venereal Disease Research Laboratory (VDRL) test. Reactive Fluorescent Treponemal Absorption (FTA-ABS) tests occurred in significantly higher frequency in pregnant women (4%) than in the general population (2.2%; p less than 0.001). The prevalence of reactive STS in children did not differ significantly from that of the general adult population. The predictive value of a reactive VDRL test in pregnant women (85%) was higher than that of the general population (79%). These results suggest that adequate screening with the inexpensive VDRL test would enable the early detection and treatment of syphilis, and could prevent increasing incidence of congenital syphilis in Jamaica. PMID- 2264333 TI - Postpartum shock and uterine inversion. AB - A 21-year-old woman, para 1 + 0, developed profound postpartum shock secondary to acute inversion of the uterus. Fundal re-inversion was achieved by prompt manual replacement of the uterus from below. An aggressive approach to uterine inversion is the keystone of success. PMID- 2264332 TI - Paediatric acquired immunodeficiency syndrome (PAIDS) in Trinidad and Tobago. AB - The first twenty-one cases of Paediatric Acquired Immunodeficiency Syndrome (PAIDS) in Trinidad and Tobago were studied. An overwhelming majority of patients were of African descent. Most of the children presented within the first year of life, the average time between presentation and death was 4 1/2 months, and the majority presented with either diarrhoea or pneumonia or failure to thrive, common conditions in the West Indies. Fever lasting longer than two weeks as well as hepatomegaly were clues which led to a definitive diagnosis. PMID- 2264334 TI - Spontaneous pneumothorax in acute paraquat toxicity. AB - Spontaneous pneumothorax as a presenting feature of acute paraquat toxicity is as yet unreported. A review of the literature has shown that there has been one reported case of spontaneous pneumothorax occurring after paraquat toxicity. In this case, the pneumothorax occurred seven years after ingestion of paraquat (Nakaoka et al, 1987). The two cases of paraquat ingestion presented in this report are associated with spontaneous pneumothorax in the acute phase. A proposed mechanism for the development of the pneumothorax is discussed. PMID- 2264335 TI - Primary hypophosphatemic rickets. An uncommon cause of bowed legs. AB - This paper describes a 9-year-old girl with primary hypophosphatemic rickets, an uncommon cause of bowed legs. A simple screening for patients presenting with bowed legs is suggested and the importance of using age-related standards for comparison of biochemical results is emphasized. PMID- 2264336 TI - Ruptured rectal prolapse. AB - Rectal prolapse is not a common surgical disorder. The complication reported here, of evisceration of small bowel through a prolapsed rectum, is extremely rare and is the first case reported in the West Indies. Some of the features of rectal prolapse are described, and the surgical management of this particular complication is discussed. PMID- 2264337 TI - [Color-coded Doppler sonography in the diagnosis of carotid artery diseases]. AB - Color-flow Doppler is a new development of duplex sonography of the peripheral vessels. In this study 844 consecutive patients were evaluated (a) to assess the comparative value of these two methods, (b) to see if there is a correlation between the degree of stenosis and the incidence of neurological symptoms and (c) to find a possible relationship between the plaque structure and the incidence of neurological deficits. (a) In 89%, the color-flow assessment was in complete agreement with the duplex assessment. In the remaining 11%, important additional results were discovered in the color flow examination. (b) Non-stenotic plaques were seen more often (43%) in the wide carotic bulb, stenotic plaques and occlusion were found more often (66 and 82%) in the internal carotic artery. Vessel occlusion was found most often in patients with cerebral ischemia. Color flow Doppler demonstrated a higher incidence of hemodynamic stenosis in patients with peripheral vascular disease, hypertension and bruits. (c) Patients with heterogeneous plaques demonstrated a significantly higher risk of neurological deficits than those with homogeneous plaques. The great advantage of color-flow Doppler is that it enables sonomorphological (plaques, stenoses, occlusion) and functional parameters (turbulences, flow enhancement) to be studied during the same procedure. PMID- 2264339 TI - [Anti-cardiolipin antibodies in venous thromboses]. PMID- 2264338 TI - [Anti-CEA immunoscintigraphy in postoperative follow-up of tumor patients. Differentiated use of various monoclonal antibody preparations]. AB - The sensitivity of immunoscintigraphy (ISC) with monoclonal antibodies (Mab) depends on the Mab type, the radiophysical properties of the isotope, the labeling method and the tumor localization. We investigated 38 studies with three different Anti-CEA Mab (In111/I131 BW 431, n = 12; I131 IMACIS-1, n = 11; Tc99m BW 431/26, n = 15) in 35 postoperative tumor patients (31 colorectal, 1 gastric, 2 breast and 1 pancreas cancer) with a total of 62 tumor manifestations. Planar ISC was used in all studies. A dual isotope technique with Tc99m-colloid was applied for imaging of liver metastases in the In111/I131 BW 431/31 and I131 IMACIS-1 studies. Whereas the global sensitivity, ranging from 64-73%, was comparable, the different physiological properties of the Mab preparations caused marked differences in the imaging capabilities of certain tumor localizations, especially in the liver. All Mab underestimated the extent of liver involvement, however, the highest regional sensitivity (75%) was found with the I131 IMACIS-1. In contrast, Mab with the highest physiological liver uptake (In111 BW 431/31, Tc99m BW 431/26) imaged liver metastases in most cases unspecifically as cold spot, yielding a sensitivity of 0-9%. No differences between the Mab were seen in the regional sensitivity with respect to lung metastases, which ranged between 33 40%. All tested Mab showed a high sensitivity in imaging local recurrences ranging between 50% for the I131 IMACIS-1 and 100% for the Tc99m BW 431/26. We conclude, that in postoperative tumor patients anti-CEA ISC with Tc99m BW 431/26 is the method of choice for the detection of local recurrences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264340 TI - [Neurosurgery]. PMID- 2264341 TI - [Development of neurosurgery in Innsbruck]. AB - The historical development of neurosurgery at the University of Innsbruck is presented, starting in 1906 with the proposed transethmoidal approach to the pituitary by H. Schloffer. The unit was founded by B. Breitner and W. Sorgo in 1947. In 1951 K. Kloss took over the unit, which grew into a university department and he became the first Professor of Neurosurgery in Innsbruck in 1972. From then on diagnostic and surgical procedures, as well as scientific research progressed rapidly. V. Grunert followed the deceased K. Kloss in 1980. Currently over 1500 major surgical procedures are performed annually according to the most modern standards. PMID- 2264342 TI - [Treatment of essential blepharospasm]. AB - A rather confusing number of conservative, as well as invasive treatment methods for essential blepharospasm are found in the literature. Depending on the severity of symptoms, two types of method became important because of their obvious success and their low rate of complications: Local injection--treatment with botulinum toxin type A in mild and moderate cases and the neurosurgical method of selective neurotomy in severe forms of blepharospasm or after inefficient application of botulinum-A toxin. The different methods of treatment are reviewed. PMID- 2264343 TI - [Steroid receptors and atypical histology as prognostic parameters in meningioma]. AB - Cytosolic oestrogen and progesterone receptors (ER and PR) were determined in 58 primary and 13 recurrent meningiomas and related to their histological and clinical features. ER levels were low or not detectable (range 0-34 fmol/mg prot., median 0 fmol), whereas considerable amounts of PR were found in 69% of primary tumours (range 0-583 fmol/mg prot., median 72 fmol) and in 5/5 long-term recurrences (range 69-505 fmol/mg prot., median 143). Eight tumours recurred within a short-term period (less than 5 years) with a low PR expression (range 0 34 fmol/mg prot., median 0 fmol) and all presented raised cellularity and mitotic rate ("atypical" meningioma) or criteria of definitely malignant meningioma. The primary tumours of the short-term recurrences were not available for receptor analysis; however, they also were either "atypical" or anaplastic meningiomas. Long-term recurrences never displayed other than classical histology. From our results we conclude that polymorphy, as well as a lack of PR are strong indicators for short-term recurrence. PMID- 2264344 TI - [Intraoperative radiotherapy of brain gliomas]. AB - 11 patients with recurrent brain tumours underwent intraoperative radiotherapy (IORT) at a dosage of 15-25 Gy of fast electrons (17-20 MEV). IORT allows a higher dose of irradiation to be delivered to a well-defined target than is possible with external radiation, in anticipation of favourable results. However, tumour growth was not influenced in 7 out of the 11 patients and these patients died between 2 and 10 months following IORT. The remaining four patients are living still up to 15 months postoperatively. Due to the inhomogeneity of our patients no definitive conclusions can be drawn. However, well-defined tumours which can be radically excised are definitely more suitable for IORT than large, infiltrating tumours. PMID- 2264345 TI - [Atraumatic measurement of intracranial pressure]. AB - This paper presents a new method for measuring intracranial pressure (ICP), which is completely non-invasive by using an isolated "headband electrode". The head itself - as a dielectric--forms a capacitor. A high frequency alternating voltage field is applied to this system (1-1.5 MHz) whereby a measuring signal is obtained which depends on the dielectric properties of the head. These, in turn, primarily depend on the filling status of the intracranial space. In addition, a pulse wave can be plotted as a result of cardiac and respiratory cycles. This combined information permits the calculation of actual ICP values with the help of a simple Basic PC programme. The measuring system was tested in 20 patients with intracranial space-occupying lesions. Their ICP values were known from invasive measurement and the obtained correlation was R = 0.983. PMID- 2264346 TI - [Eosinophilic bone granuloma in an 8-month-old infant]. AB - A solitary eosinophilic granuloma in an 8 month-old infant is presented. The tumour, which had penetrated bone dura, but spared the brain tissue was radically excised. This case shows an unusually low age of presentation of this rare disease, and an unusual endocranial extension of the tumour. If an infantile eosinophilic granuloma is suspected, then computerized tomography should always be performed. PMID- 2264347 TI - [Problems in diagnosis and therapy of extensive intramedullary tumors (illustrated by a case report)]. AB - The case is presented of a patient with intramedullary ependymoma extending from C 1 to D 5, treated by a three-stage surgical procedure. A historical review is provided, followed by a discussion of the difficulties of diagnosis, especially at an early stage, and of the surgical management. PMID- 2264348 TI - [Short definitions of medical concepts. 4. Brain death]. PMID- 2264349 TI - [Brain death from the viewpoint of transplantation surgery]. AB - If in the case of brain death breathing and circulation are continued artificially we deceive ourselves emotionally not to except death of the so treated organism. But on scientific medical grounds brain death defines the end of the organism as a whole beyond doubt. No rational reasons can be seen, why organs should not be taken from the brain dead provided that diagnosis of brain death and the organ retrieval are done by independent teams of doctors and an opposing will of the dead person is not known. Honour should be payed to the remains of the dead organ donor. Donation of living donors should be seen more critically because of the ethical problems involved for the managing doctors. PMID- 2264350 TI - [Is brain death actually death?]. AB - The paper rejects "brain death" as a new criterion, or definition, of actual death. The main theses are two: 1. Brain death as such--in any of its meanings- is not man's death and this can be proven by means of many cogent and some plausible arguments. 2. Even if the theoretical arguments against the identification of man's actual death with brain death did not demonstrate their non-identity, the opposite position would still be uncertain, at least. In view of this undeniable fact, a minimal ethical responsibility demands that we must not act, by organ retrievals, on the assumption of the identity of "brain death"- in any of its meanings--with man's actual death. We must avoid those actions which, like killing, presuppose a high degree of moral certainty concerning death, given that we cannot attain such certainty, as in the case of brain death. Thus organ and heart-explantations are found to be unethical. A newly thought out notion of biological death of the human organism as a whole ("clinical death" as irreversible cessation of all vital bodily functions, in particular of cardiopulmonary and cerebral functions) is proposed as theoretically best founded and ethically safest medical criterion of death. PMID- 2264352 TI - [Intravaginal culture--simplification of IVF]. AB - Initial results with intravaginal cultures (IVC) of human oocytes are reported. Up to 5 oocytes are harvested by follicular puncture guided by transvaginal sonography. Together with washed spermatocytes (final concentration 0.1 to 0.15 x 10(6)/tube) these are transferred to a plastic capsule filled with Menezzo B2 medium. After air-tight closure the capsule is placed into the patient's vagina and left in situ for 48 to 52 hours. Capsule loss is prevented by plugging the vagina with a tampon of appropriate size. In the first 15 females undergoing IVC fertilization was obtained in 56% of cases. Three intact pregnancies were recorded after embryo transfer. Of these, 2 occurred in the group of patients with tubal infertility and one in the group with tubal infertility and an additional andrologic abnormality. Our results and the reports by others suggest that IVC may well facilitate the technique of IVF. Potentially detrimental effects of light exposure and temperature variations on the gametes during conventional IVF are minimized. The more active involvement of the patients is an added psychological benefit. PMID- 2264351 TI - [Historical development of the Radiology Department of the 1st and 2d University Women's Hospital Vienna]. AB - A historical review is given on the installation of the Department of Radiotherapy of the 1st Department of Obstetrics and Gynecology and its further development to the Department of Irradiation of the 1st and 2nd Department of Obstetrics and Gynecology at the Vienna University. The milestones of the last 40 years like the change to the "New Stockholm Method" (1954), the new construction and adaptation (1968-1972) with the installation of a telecobalt-therapy-unit (1972), the conjunction of the department of radiotherapy of both university departments to a single department in the same year and finally the introduction of the after-loading method in brachytherapy (1980) are pointed out specifically. PMID- 2264353 TI - [The significance of postoperative radiotherapy in cervix and uterine cancer]. AB - The benefit of adjuvant radiotherapy of operated cervical and endometrial cancer is not clear. In a prospective trial of 571 endometrial cancers stage I, cases with poor prognosticators are treated additionally with external pelvic irradiation (Co 60, 56 Gy) and show nearly the same outcome as cases with good prognosticators and without such an adjuvant therapy. A benefit of adjuvant irradiation of cervical carcinoma stage I/b could only be shown in cases with similar histopathologic characteristics (tumor volume, grading, vessel invasion, lymphnode involvement). In a retrospective study 171 cases of cervical carcinoma were analyzed. With adjuvant external irradiation the relapse free interval was longer and 5-year survival better than without such an adjuvant therapy. PMID- 2264355 TI - [Cough--physiologic reflex and symptom of illness]. PMID- 2264354 TI - [The significance of primary radiotherapy in gynecological carcinoma. An account of 40 years]. AB - The Department of Gynecological Radiotherapy of the University of Vienna is headed since 40 years by Prof. Dr. Karl Weghaupt. In this time about 25,000 cancer cases were treated, 12,000 of them by radiation alone. Local therapy was performed by conventional Radium-226 irradiation, which has to be replaced by remote afterloading technique. Therapy modalities have not been changed and therefore an extraordinary high number of cases is available for 5 year survival rates. Results of new radiologic techniques will have to be compared to these fundamental data. Due to radioprotective regulations replacement of Radium-226 is necessary but there will not take place any change in treatment politics in cases of vulvar carcinoma. PMID- 2264356 TI - [Praziquantel is mostly ineffective: treatment of fasciola hepatica infection (large liver fluke)]. PMID- 2264357 TI - [Current status of lymphography among imaging methods]. PMID- 2264358 TI - [Histologic assessment of gynecologic tumor recurrence by puncture biopsy]. PMID- 2264359 TI - [Inpatient medical management, 1988 compared with 1978]. PMID- 2264360 TI - [Heinrich Finkelstein, born 125 years ago]. PMID- 2264361 TI - [Assessment of diagnostic lung function parameters in underground workers exposed to diesel gas]. AB - Evaluations of lung function parameters were carried out in underground miners with outstanding exposition to diesel exhaust by diesel-driven machines. Data obtained over a three year period were compared with the results of a non-exposed population. There were no differences between both groups following to the influence of diesel exhaust. PMID- 2264363 TI - [Reference values of Na(+) and Cl(-) concentrations in adult sweat]. AB - The results of the investigations to reference values for Na(+)- and Cl(-) concentrations in sweat of adults are as follows: The normal range of electrolyte values in sweat in adults is up to 70 mmol/l (Na+) and 55 mmol/l (Cl-) respectively in infants (40 mmol/l for Na+ and Cl-). There are no sex and age differences. Adults with chronical bronchitis and bronchiectasis don't show different results in comparison with healthy persons. Adults with cystic fibrosis have significantly increased sweat electrolyte concentrations (90-120 mmol/l). Variations in the electrolyte values of a day or of a month are important and much higher than the analytical one. PMID- 2264362 TI - [Comparative study of parenteral and oral immunization to influenza in a large clinical trial. 1. Results of clinico-epidemiologic studies]. AB - 360 volunteers were recruited for the investigation from a homologous collective. 174 were immunized parenterally with "Influmun" from SSW Dresden, GDR. 176 volunteers were immunized twice orally with an interval of 60 days with an influenza vaccine inactivated by x-ray using enteric-coated capsules. In an interval of six months ARI-symptoms were investigated. Between 13th and 17th week 1988 an increased ARI-morbidity in the Greifswald-region was observed in which influenza A viruses were involved. In comparison with 312 non-immunized persons of the same age, sex and living area the immunized volunteers of the two groups showed 83.4% less sickness days. 30 persons of the non-immunized group got ill for totally 217 days, whereas only nine persons of the two immunized groups were put on the sicklist for totally 36 days. No significant differences concerning the occurrence and duration of acute respiratory infections (ARI) between the two differently immunized groups could be observed. PMID- 2264364 TI - [Chemiluminescence measurements of bronchoalveolar lavage cells in patients with collagenosis]. AB - The purpose of the study was to determine the role of reactive oxygen metabolites in the pathogenesis of interstitial lung involvement in 13 patients with collagen vascular diseases (CVD) in comparison with 10 control subjects. The cellular activity of bronchoalveolar lavage (BAL) cells was measured by means of chemiluminescence (CL), spontaneously and after challenge of the cells with opsonized zymosan (simultaneously luminol- and lucigenin-dependent). The findings show an increase of the spontaneous and stimulated CL of BAL cells in CVD, more pronounced in luminol-dependent CL. The luminol-dependent CL correlates with neutrophils in BAL cell differentiation. The results suggest that reactive oxygen metabolites take part in interstitial lung involvement in patients with CVD. Therefore the measurement CL of BAL cells is useful in addition to BAL cell differentiation in diagnostic of interstitial lung involvement in CVD. PMID- 2264365 TI - [Cholesterol granulomatosis of the lungs]. AB - The cholesterol storage disease of the lung is seldom and therefore we hardly think of it. An evident diagnosis can be given only by histological examinations. 2 cases are described where during life was diagnosed a silicosis and declared as an occupational disease. Autopsy revealed cholesterol storage disease without any signs of silicosis. These findings suggest, that in cases with low occupational quartz-dust-exposure it is advisable to extend the field of diagnostic procedures. PMID- 2264366 TI - [BCG osteomyelitis and arthritis]. AB - Since 1980 an increase of the frequency of osteomyelitis after BCG vaccination has been described by some european countries. In the GDR osseous impairments as BCG complication are rarely. The authors report on an 18 months old boy with lesions of the distal tibia and the ankle-joint. He was vaccinated with BCG in the neonatal period. In contrast to the local findings general symptoms were unimportant. The surgical treatment was completed by antituberculotic chemotherapy. This treatment was successful. PMID- 2264368 TI - [Mycological nomenclature]. PMID- 2264367 TI - [Oral administration of "Infectvac" for prevention of acute respiratory tract infections]. AB - The efficacy of a newly developed polyvalent bacterial lysat vaccine "Infectvac" was tested in experimental studies in animals. It was shown that a local application (oral, aerogenic) prevent the animals from a lethal bacterial (S. pneumoniae) or viral (A/PR/8/34) infection. In first clinical trials a good compatibility of the drug was demonstrated. PMID- 2264369 TI - [Effect of urea on penetration kinetics of vitamin A acid in human skin]. AB - It is well known that urea can considerably increase the release of drugs from ointment bases and that it is one of the most effective penetration promoters for topically applied drugs. In our present study, therefore, we investigated the influence of urea on the penetration kinetics of vitamin A acid (VAA) into the various layers of human skin. When a vehicle containing urea was applied to the skin, we found increased VAA concentrations depending on the penetration of urea. We discuss the significance of the synergistic properties of VAA and urea in the topical treatment of various skin disease. PMID- 2264370 TI - [Effect of cignolin and infrared irradiation on the patch test and lymphocyte transformation test]. AB - In a study on the effect of anthralin and infrared irradiation (IR) on the allergic patch test in vivo and the lymphocyte transformation test in vitro, we observed that anthralin enhanced the local test reaction. Our findings suggest an additive reaction of toxic anthralin dermatitis and allergic test reaction. Immunohistology showed that additional treatment with anthralin resulted in elevated numbers of the OKT-6+ dendritic cells in the epidermis. Anthralin in concentrations of greater than or equal to 10(-5) M inhibited the lymphocyte transformation in vitro. IR irradiation-either before or during patch testing-did not significantly influence the allergic test reaction or the lymphocyte transformation, if the temperature was adjusted to 37 degrees C. In comparison to convective heat, we found no specific effect of IR irradiation. PMID- 2264371 TI - [Beta-2-microglobulin expression in oral lichen planus]. AB - In 15 patients suffering from oral lichen planus (OLP), we took biopsies of both involved and noninvolved oral mucosa. The specimens were immunohistochemically studied with regard to the expression of beta-2-microglobulin (beta 2-M). In contrast to noninvolved mucosa, we proved definite beta 2-M expression in keratinocytes from OLP lesions. Our findings agree with the assumption that an autoimmunological process is involved in the pathogenesis of OLP. PMID- 2264372 TI - [Psoriatic osteopathy--results of histomorphometric studies]. AB - In 23 patients with psoriatic arthritis and 9 patients with psoriasis without joint involvement, we took bone biopsies from the iliac crest. Histomorphometrical investigations showed that the volume density of the bone was not decreased in either group of patients, but we found a high rate of turnover remodelling. An elevated rate of bone turnover is regarded as the characteristic principle of "psoriatic osteopathy", which--more exactly--should be called "latent osteopathy". Deficiency of vitamin D is discussed as a possible etiological factor. PMID- 2264373 TI - [Hydroxyproline excretion in psoriasis and psoriatic arthritis]. AB - In the morning urine of 24 patients with psoriasis and that of 24 patients with psoriatic arthritis, we determined the excretion of hydroxyproline (mg HP/mumol crea), after preceding diet low in collagen. Surprisingly, psoriatic patients without articular involvement showed a significantly higher excretion of HP than those with psoriatic arthritis. Further differentiation revealed that there were no clear-cut correlations between the amount of HP excretion and the activity of the articular process; we proved, however, that the amount of HP excretion was definitely related to the activity of the skin eruptions in both groups of patients. We discuss whether an osteopathy pathogenetically associated with the skin disease (irrespective of synovitis in psoriatic arthritis) may possibly be responsible for these results. PMID- 2264374 TI - [Pruritic urticarial papules and plaques in pregnancy]. AB - PUPP is a specific eruptive dermatosis in pregnancy, clinically characterized by erythematous papules and plaques with intense itching in periumbilical localization. This disease typically tends to spread to the extremities without involving the head and neck regions. The differential diagnosis of PUPP can be established by immunological and microscopical investigations. Since PUPP is a benign disease with a good prognosis and spontaneous clearing, we recommend only mild symptomatic treatment. PMID- 2264375 TI - [Squamous cell carcinoma of the lower lip in discoid lupus erythematosus associated with hereditary deficiency of complement 2]. AB - We report on a 48-year-old female patient suffering from lupus erythematosus associated with C2 deficiency, who developed squamous cell carcinoma on a discoid lesion of her lower lip. Vermilionectomy (Langenbec-v. Bruns' technique) resulted in a good cosmetic and functional outcome. PMID- 2264376 TI - [Surgical reduction in benign symmetrical lipomatosis]. AB - We report on a 50-year-old female patient suffering from benign symmetric lipomatosis of her upper arms, shoulders, neck, back, abdomen, and thighs. Concomitantly, we found hypertension, hyperuricemia, and hypertriglyceridemia. Since the patient complained of occasional pain in her upper arms and shoulders induced by work or pressure and suffered psychically from her deformity, we decided to reduce the fatty tissue of the upper arms surgically--with good cosmetic and functional results. PMID- 2264377 TI - [Cutaneous manifestation of Crohn disease]. AB - In a 20-year-old women having suffered from Crohn's disease for many years, we found granulomatous fistular ulcerations on her right distal lower leg. After histological verification of the clinical diagnosis, she was orally treated with metronidazole for 6 weeks with excellent results: The cutaneous lesions healed completely. PMID- 2264378 TI - [Kyrle disease--a case report]. AB - Based on a case of our own observation, we present the characteristic features of a rare skin disease: hyperkeratosis follicularis et parafollicularis in cutem penetrans, i.e. Kyrle's disease. The clinical picture shows follicular and interfollicular hyperkeratotic horn-like plugs with a typical distribution pattern. The classical histological features are epidermolysis and hyperkeratoses advancing towards the dermis. Today, this disease is regarded as a genodermatosis with recessive heredity and is best treated with systemic and topical application, resp., of vitamin A acid. PMID- 2264379 TI - [Immunogenetic approaches to the study of leukemia in humans]. AB - One hundred and ten families having one child suffering from acute leukemia were included in HLA studies. These families were found to have unequal distribution of the parent HLA-haplotypes among the sibs. Three groups of families were conditionally distinguished. The first group showed the predominance of one parental, the second group of one maternal, and the third group of one maternal and one paternal HLA haplotypes. This suggests that impairment of the evolutionally derived principle of equal participation of both gamete types of each parent in the zygote formation is deleterious for the progeny. PMID- 2264380 TI - [Immunocorrective therapy of hematologic diseases]. AB - Changes in the immunological parameters have been studied in the course of treatment with antithymocytic globulin and chemotherapeutic preparations included in the treatment protocols for aplastic anemia and acute leukemia. A possibility of determining the optimal immunocorrective agent dosage is demonstrated as related to its effect on the functioning of the immunocompetent cells in vitro. PMID- 2264381 TI - [Biological principles of the therapy of acute leukemia]. AB - The biological features specific to the tumor growth in acute leukemia are responsible for the disease prognosis and its response to polychemotherapy. Current molecular-biological, karyological, cytological, kinetic, and culture investigation techniques have contributed much to the understanding of the pathogenesis of acute leukemia and may be used as a guide to appropriate disease management. PMID- 2264382 TI - [Non-Hodgkin's malignant lymphomas in primates (immunodiagnostic principles in T cell lymphomas)]. AB - Morphological and immunological phenotyping was carried out on 20 cases of peripheral baboon T-cell non-Hodgkin's malignant lymphomas (NHL) observed in a Sukhumi monkey colony. Morphologically, the lymphomas were prolymphocytic, immunoblastic, or rarely lymphoblastic types. For immunophenotyping studies, the panel of 29 monoclonal antibodies (MAb) to human or mouse leukocytic antigens were used (18 CD clusters). Three polyclonal sera to human IgG and light chains kappa and lambda were also taken in experiments. The investigated NHLs and CD4+CD8- (12 cases) or CD4-CB8+ (5 cases) phenotypes. In some cases loss of pan T cell antigens or unusual antigen expression--loss (one case) or coexpression (two cases) of T-subset antigens--or the presence of abnormal lymphoid antigens have been revealed. In most studies, baboon T-cell NHLs tumor cells belonged to activated T-cells because they expressed Ia-like antigens and IL2R at high levels. There was no correlation between the discovered immunophenotype and the morphological pattern of malignant lymphomas. PMID- 2264383 TI - [Lymphocyte-macrophage regulation of reparative erythropoiesis]. AB - Experiments on mice have shown that the peritoneal cells and splenocytes transferred from anemic animals to normal syngenic recipients cause the appearance of signs of blood formation by the reserve erythropoiesis type, i.e. a decrease of the mitotic index in basophilic erythroblasts and appearance of mitotic oxyphilic erythroblasts. The capacity of peritoneal cells (PC) to transfer this type of the cell differentiation becomes manifest at 30 minutes, achieves its maximum at 2-4 hours, and becomes somewhat reduced at 48 hours after the blood loss. The transfer effect depends on the dose of introduced cells. The PC transfer capacity is higher than that of splenocytes. The lymphocyte inactivation by monoclonal anti-Thy-1,2 antibodies reduces the PC transfer capacity, which is indicative of the role played by the cell cooperation in promoting the transfer effect. Stimulation of erythropoiesis under the effect of macrophages and lymphocytes taken from anemic donors is significant and is accompanied by increased numbers of erythroid cells in the bone marrow and of reticulocytes in the peripheral blood. PMID- 2264384 TI - [Perspectives of the use of bioluminescence methods in medicine]. AB - Major advances in the development and application of the bioluminescent analysis to detect certain biologically active substances are discussed. The main merit of the method lies in its high sensitivity and specificity along with its simplicity and rapid performance. The available methodologies allow for detection of substances of varying nature: Ca2+, ATP, FMN, NAD(P), long-chain aldehydes, ATP- and NAD(P)-dependent enzymes and their substrates, many xenobiotics and antibiotics, and mutagens. The bioluminescence methodologies may be widely applied in clinical laboratory diagnosis. PMID- 2264385 TI - [Primary hemopoietic stem cell]. AB - A complex of experimental original laboratory findings is presented to demonstrate a restricted proliferative potential of stem hemopoietic cells. Development of new methodologies to study primitive stem hemopoietic cells, i. e. the cells that are responsible for maintenance of continuous blood formation, allowed for confirming their existence, assessing their content in the hemopoietic tissue, determining the time and site of their embryonic origin, and for showing their limited capacity for regeneration. The obtained evidence is important for the understanding the mechanisms governing hemopoiesis. PMID- 2264386 TI - [Effects of embryonal bone tissue on hemopoiesis]. AB - The influence of human fetal bone (FB) on the hemopoietic and stromal cells were studied in the morphometric assay of the bone marrow trephine biopsy samples after a preliminary cultivation using the Marbrook system for 1-5 weeks. The rat FB effect on the hemopoiesis and survival were also studied in experiment with FB transplantation to rats with prior administration of lethal and sublethal doses of cyclophosphamide. In long-term cultivation of the bone marrow trephine biopsy samples, enhanced proliferation of the fibrous tissue and elimination of hemopoietic elements were seen. Combined cultivation of the trephine biopsy samples of the bone marrow and FB inhibited the fibrous tissue proliferation and enhanced the viability of the hemopoietic and lipid cells. Transplantation of the FB in experiment shortened the leukocytopenia period in rats after sublethal (300 mg/kg) and lethal (500 mg/kg) doses of cyclophosphamide and increased their survival. PMID- 2264387 TI - [Blood aggregation regulation system and hematopoiesis]. AB - Conditions favoring the formation of pathological systems of blood aggregation control (BAC) in hemopoiesis defects are overviewed. Major pathological BAC systems are characterized including hematogenic thrombophilias, thrombohemorrhagic syndromes, and pathological diatheses. The relationships between these pathological systems and blood formation defects are analysed, and recommendations are presented on the use of extracorporeal blood aggregation control for the destabilization and reduction of pathological BAC systems. The techniques of extracorporeal BAC are based on the gravitation surgery of blood and are highly effective in the management of patients with certain forms of hemoblastosis, crush and thrombohemorrhagic syndromes, and severe ischemic heart disease. These techniques are not specified as blood purification procedures, but belong to a higher-class group of methodologies including blood reconstruction and hemoengineering. Research into the intersystem relationships in disease is of high practical value. This particularly refers to the determination of the pathological system limits, its components, determinant, and formation of an antisystem. PMID- 2264388 TI - [Hormonal mechanisms of the regulation of thrombocytopoiesis]. AB - The role played by the adrenals and the insular apparatus of the pancreas was studied in experiments on dogs. It was found that prednisolone and adrenaline enhance thrombocytopoiesis while unilateral adrenalectomy suppresses it. Bilateral adrenalectomy brought about an increase in the number and functioning of thrombocytes along with a drastic reduction in megakaryocyte counts. Pancreatectomy and alloxan diabetes were associated with sharp thrombocytopenia with decreased daily thrombocytopoiesis and megakaryocyte counts. Administration of insulin to intact dogs was attended with an increase in megakaryocyte counts and in the adhesive and aggregation function of thrombocytes. Insulin was found to stimulate thrombocytopoiesis under medicamentous thrombocytopenia. PMID- 2264390 TI - [Suppurative-inflammatory diseases in newborn infants]. AB - Changes in the etiological patterns of suppurative-inflammatory diseases of neonates during 1978-1988 were analysed. Basic trends in the etiological structure changes, growing numbers of individual microorganism families or species, and changes in the clinical manifestations corresponding to the etiology variation were demonstrated. Preventive antibiotic therapy administered to neonates in the maternity hospital is proved ineffective, and its deleterious effect on the postnatal microbial colonization is shown. PMID- 2264389 TI - [Long-term consequences of the damaging effect of cytostatic drugs on hematopoiesis and lymphoid tissue]. AB - The evidence on the changes detectable in remote periods (at 1, 3, and 6 months) is presented. It shows that the quantitative and functional defects are retained in the hemopoietic and lymphoid tissues within 3-6 months after exposure to the effects of various cytostatic agents. These defects may be corrected by means of immunomodulators. PMID- 2264391 TI - [Role of chromosome aberrations in the development of leukemic process]. AB - The pathogenetic and clinical significance of karyotype features in leukemia and preleukemia are analysed. In 34.7 per cent patients with preleukemia, karyotype instability was observed which consisted in numerical and structural chromosome aberrations with clone anomaly. It was found that karyotype instability is an initial stage of anomalous clone formation and often precedes its development in preleukemia, secondary leukemias, and in preblastic stage of chronic myeloid leukemia. Acute leukemias were found to be characterized by premeditated numerical and structural chromosomal aberrations with predominant involvement of chromosomes 5, 7, 8, and 21 in non-lymphoblastic and chromosomes 6, 9, 8, and 21 in lymphoblastic forms of acute leukemia. It was also shown that the normal to abnormal metaphase ratio in acute leukemia patients is of high prognostic value. PMID- 2264392 TI - [Long-term effects of postnatal hypoxia on monoamine and amino acid levels in the rat brain]. AB - Perinatal hypoxia is known as a risk factor for human epilepsies. Previous studies in our laboratory have shown that the rats with postnatal hypoxia show facilitation of the kindling formation and enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures even after the maturation. In the present study, the effects of postnatal hypoxia (100% N2, for approximately 5 min, at ten days of age) on monoamine and amino acid levels in the brain of adult rats (three months of age) were investigated to clarify the biochemical basis of the enhanced seizure susceptibility. In the hypoxia-treated rats, norepinephrine (NE) was significantly decreased in the pons-medulla (82% of control) and hypothalamus (85%) as compared with controls. Dopamine (DA) was decreased in the pons-medulla (83%). A decrease in DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was also noted in the substantia nigra (71%) and hippocampus (64%), respectively. On the other hand, gamma-aminobutyric acid (GABA) was significantly increased in the striatum (121%). These findings indicate that the enhanced seizure susceptibility in these rats may be attributed to 1) impaired development of noradrenergic and dopaminergic neurons, of which these transmissions are known as inhibitory modulators of seizure discharge in some animal models of epilepsies, and 2) changes of GABAergic and dopaminergic transmissions in the striato-nigral pathway, which is a wellknown regulation system for seizure propagation. PMID- 2264393 TI - [Effects of scopolamine and diazepam on delayed discrimination behavior in rats]. AB - The effects of subcutaneously administered scopolamine and diazepam on simultaneous as well as delayed light-dark discrimination behavior were studied in a Y-maze situation using rats. In simultaneous discrimination behavior, running responses to the lighted side of either the right or left arm of the Y maze were regarded as correct choices. In delayed discrimination behavior, running responses to the lighted side at several delay times (0. 2, 4, and 8 sec) after extinguishment of the light were regarded as correct choices. In the saline test, the percentage of correct choices decreased as the delay time was extended. Scopolamine at 0.03 mg/kg decreased the percentage of correct choices as the delay time was extended within the range of 0 sec through 4 sec. Diazepam both at 1 mg/kg and at 2 mg/kg decreased the percentage at the delay times of 0, 2, and 4 sec but this decreasing effect was not dependent on the delay time. The same doses of these drugs had no effect on simultaneous discrimination behavior. These results suggest that scopolamine at 0.03 mg/kg and diazepam both at 1 mg/kg and at 2 mg/kg disrupt delayed discrimination behavior in different ways. PMID- 2264395 TI - [Aging-induced changes of acetylcholine and choline contents in cerebrospinal fluid and memory function]. PMID- 2264394 TI - [Behavioral teratogenesis and placental, milk, and blood-brain barrier transfer following prenatal and postnatal exposures to chlorpromazine in rats]. AB - In order to determine behavioral teratogenesis of fetal and neonatal exposures to chlorpromazine (CPZ) in rats, conditioned avoidance learning by shuttle box in pups was examined. CPZ was administered sc to pregnant and nursing rats during fetal organogenesis period (on days 11-15 of gestation, at doses of 9, 21 mg/kg/day), perinatal period (on days 16-20 of gestation, at 9, 18 mg/kg/day), and nursing period (on days 1-10 postpartum, at 9, 18 mg/kg/day). The results showed that high doses of CPZ during all periods caused learning impairment in pups, although learning impairment by the exposures during fetal organogenesis and nursing periods was stronger than that of perinatal exposure and pattern of learning impairment was different between the former and the latter. Exposure to CPZ during fetal organogenesis period induced an increase in norepinephrine and dopamine concentrations in the hippocampus of pups. Thus it is clear that developmental treatment with CPZ produced learning impairment. Furthermore, CPZ transferred rapidly into fetal and neonatal brains. Our results suggest that blood-brain barrier transfer of CPZ is a major factor in behavioral teratogenesis. PMID- 2264396 TI - [Modulation of brain function by opioids: with special reference to learning and memory process]. PMID- 2264398 TI - A simple, rapid and simultaneous analysis of complex volatile hydrocarbon mixtures in blood using gas chromatography/mass spectrometry with a wide-bore capillary column. AB - A screening method for detecting volatile hydrocarbons in blood has been developed using gas chromatography/mass spectrometry with a wide-bore capillary column and a headspace method. Toluene-d8 and indan were used as the internal standards for quantitative analysis. Hydrocarbons with retention indices from 600 to 1200 were simultaneously and quantitatively detected in relatively low concentrations (0.01 microgram/ml) in reconstructed ion chromatography. This method could prove useful in forensic cases in which urgent examination of complex hydrocarbon mixtures, e.g. petroleum components, is required. PMID- 2264397 TI - Distribution of A and B antigens in organs of blood group AB individuals: observations disclosed by a double immunoenzymatic labeling method. AB - The localization of A and B antigens in the organs of blood group AB individuals has been studied using a double immunoenzymatic labeling method. Both A and B antigens were found in the various epithelial cells of these organs, but the epithelial cells could be classified into the following four types depending on the reaction pattern with anti-A and anti-B sera: type 1: cells that stained positive with both anti-A and anti-B sera; type 2: cells that stained positive with anti-A serum only; type 3: cells that stained positive with anti-B serum only; type 4: cells that were negative with both sera. The distribution of each of these epithelial cell types varied considerably, even in the same tissue and individual. Our results seem to suggest that a dissociation in the conversion to the A and B antigens occurs in the tissue of individuals belonging to blood group AB and that the degree of this dissociation varies from tissue to tissue and from cell to cell. PMID- 2264400 TI - Comparative study of the sensitivity and specificity of the zinc and acid phosphatase spot tests for the detection of seminal stains. AB - The sensitivity and specificity of a zinc spot test for the detection of semen were compared with those of an acid phosphatase detection method. As screening techniques both tests were found to be very sensitive, but the zinc test was more specific and was more reliable in older and especially in deteriorated specimens. It is concluded that the zinc spot test deserves at least the same place as the acid phosphatase test in the primary investigation of suspected semen stains and might well be the test of choice in older and poorly preserved stains. PMID- 2264399 TI - [Interpretation of postmortem digoxin levels: evaluating a "corrective factor" for postmortem blood digoxin concentration]. AB - Interpretation of postmortem serum digoxin levels is made difficult above all by a possible prefinal or postmortem rise in digoxin concentrations in the blood. To compensate for this postmortem increase, Eriksson et al. (1984) divided the level of postmortem digoxin in femoral venous blood by a factor of 1.5; in the opinion of these authors, postmortem digoxin levels still exceeding "therapeutic levels" after division by 1.5 are an index of digoxin overdose. The diagnostic value of this "correction factor" was investigated. In 56 cases with documented digoxin medication, samples of postmortem femoral venous blood were taken and the level of digoxin determined. In none of the cases had there been a clinical diagnosis of digoxin intoxication. Fifty percent of the measured values were above "therapeutic levels" (0.7 ng/ml to 2.2 ng/ml). Following division by 1.5, 20% of the cases still showed levels exceeding 2.2 ng/ml; the highest "corrected" value was 4.44 ng/ml. Taking into account the length of time between final dosage and death, individual differences in sensitivity to digitalis glycoside, and the complexity of ante- and postmortem dispersion processes, we concluded for the cases we studied that an (undetected) digoxin overdose was not even likely in those cases whose postmortem values after division by 1.5 lie above "therapeutic levels". The "correction factor" proposed by Eriksson et al. (1984) is only of limited diagnostic value; at best the "corrected" values can give an approximate indication of the corresponding antemortem serum digoxin concentrations. In particular, "corrected" values only a little above "therapeutic levels" could not confirm suspicion of an overdose with sufficient certainty. PMID- 2264401 TI - [A1 and A2 blood group substances: are there structural differences?]. AB - Blood group substances were extracted from erythrocytes of blood groups A1 and A2 and separated using HPTLC. Identification of blood group A was carried out on the chromatogramm using the PAP-technique. The specific demonstration of the serologically active glycosphingolipids allowed a comparison of the A1 and A2 blood group substance bands. The difference between the A1 and A2 Substances appears to be only a quantitative one. PMID- 2264402 TI - [Explanation of nonspecific serologic reactions in decomposed bone tissue]. AB - Bone fragments were stored in water for 2 years at room temperature and investigated serologically using the following methods: Absorption-elution, extraction of blood group substances and immunohistochemistry (PAP). All 3 methods gave essentially specific results for fresh bone tissue but with putrid bone tissue unspecific reactions were found predominantly with the absorption elution and PAP techniques. In contrast, more specific reactions were obtained from the extracts although they were much weaker. From this it can be concluded that pure physical binding plays a substantial role in the unspecific reaction between antibodies and bone material. It is suggested that the relevant physical properties are altered by putrification. PMID- 2264403 TI - Analysis of inflammable substances to determine whether death has occurred before or after burning. AB - In two murder cases involving burning, both victims had been set on fire in the open air after being drenched with kerosene. In the first case, carbon monoxide hemoglobin (COHb) saturation was found to be 2.1% in the left heart blood and 0.8% in the right heart blood, a ratio of 2.6 for left to right heart blood. Paraffin hydrocarbons were also detected in the left heart blood. It was determined that the victim had been set on fire before death and that burning had been the cause of death. In the second case, the COHb saturation was 0.21% in the left heart blood and 0.24% in the right heart blood, giving a left-to-right ratio of 0.9. Paraffin hydrocarbons were detected in the hair sample, but not in the left heart blood. It was determined that the victim had been set on fire after death, and the cause of death was suspected to be asphyxia due to compression of the neck. PMID- 2264405 TI - [General prevention of osteoporosis--yes or no?]. PMID- 2264404 TI - [Glyphosate utilization by Pseudomonas spec. GS]. AB - Pseudomonas spec. GS grown in the presence of 14C-labelled glyphosate metabolizes the herbicide to inorganic phosphate as well as in respect of utilization of the C-skeleton. Furthermore it was shown that the primary step of degradation is the breakdown of the C-P-bond, because sarcosine was found as a transient metabolite. PMID- 2264406 TI - Three years experience with local hydrocortisone treatment in women with immunological cause of infertility. AB - Two high selected groups of infertile women with proved cervical spermagglutinating antibodies by ficin, sucrose gradient ultracentrifugation, ELISA and microagglutinating test, by indirect MAR-test had been chosen for local hydrocortisone treatment. In the first group being composed of 20 infertile women we registered 16 decreasing or total disappearance of antisperm activity in cervical ovulatory mucus. Ten of them delivered healthy child. New 27 selected patients have treated in their immunological failure of reproduction by local hydrocortisone application, too, two of them are pregnant now. During the local hydrocortisone immunosuppression no side effects were registered. Hydrocortisone treatment seems to be a very perspective method in regulation of cervical immunological cause of infertility. PMID- 2264408 TI - Increased placental phospholipase A2 activities in pre-eclampsia. AB - Phospholipase A2 activity was significantly increased in placental homogenates from 22 patients with pre-eclampsia in comparison to placental homogenates from women with uncomplicated pregnancy. Such an abnormality may be responsible for an altered release of free arachidonic acid, thus playing a major role in the pathogenesis of this syndrome. PMID- 2264407 TI - [Resorption of iron in steady-state conditions following administration of Vitaferro to females with anemia in pregnancy and evaluation of hematologic and biochemical iron parameters]. AB - Determination of ferritin is suitable for estimation of iron stores as well as for diagnosis of iron deficiency during pregnancy. It shall be used preventively in the 20th gestational week and to control treatment. Determinations of serum iron concentration, iron binding capacity and partial transferrin saturation are less suitable. Substitution of iron should start when a sufficient compensation of the iron deficiency is still possible. For this purpose Vitaferro is a suitable drug. PMID- 2264409 TI - [Liver diseases and pregnancy]. AB - 221 from 161,674 pregnant women had been hospitalized because of suspicion of virus hepatitis. That is a frequency of 1.4%o. Confirmation of diagnosis was made by histology in 18.5 per cent. The rate of low birth weight infants of 24.2 per cent and the frequency of 13.4 per cent of obstetric operations refer for a diminished placental function. Questions of diagnostics and the course of pregnancy in the combination of liver diseases and pregnancy are discussed. PMID- 2264410 TI - [Computer-assisted quality control in surgical gynecology]. AB - A simple and in the practice well working program of registration and interpretation for analysis of perioperative results in the gynaecology was elaborated by integration of computer on the working-place. The possibility of this perioperative analysis should be established in every hospital with introduction of documentation by employment of computer. Unitary documentation and definitions are the premise of the critical explanation with the own data and comparison with the results among the other hospitals. PMID- 2264411 TI - [The startle reaction of the newborn infant]. AB - Startle characterized by a spontaneous or reflecting motoric symptom like brisk, shortlasting and generalized contraction of limb and trunk muscles influence considerably the cardio-respirogram of neonates. The dependence of startles on behaviour, gestational age and postnatal age as well as on levels of blood glucose, calcium and magnesium in serum has been studied in 12 premature infants and in 24 full term neonates by means of polygraphic conditions. The average of 3.6 +/- 3.0 complete startles in premature infants and of 10.6 +/- 8.7 startles in full term neonates per hour non rapid eye movement-sleep, observed on second day after birth, was significantly higher than the frequency of startles in rapid eye movement-sleep measured as 0.6 +/- 0.9 and 1.9 +/- 2.1 complete startles respectively. In an age of 4 weeks there were no complete startles demonstrable in full term neonates and only 0.2 complete startles/h in non rapid eye movement sleep could be observed in premature infants. There was no correlation between frequency of startles and investigated chemical parameters in serum. PMID- 2264412 TI - [Acinetobacter as a problem pathogen in patients with long-term tocolysis]. AB - A hospital outbreak of Acinetobacter Calcoaceticus in a ward with patients with intravenous tokolysis is reported. Within 2 months 9 pregnant women who had tokolysis for premature labour developed septic fever that only subsisted after the administration of tokolysis was stopped. In 7 cases blood culture was positive for Acinetobacter Calcoaceticus. This endemic outbreak was responsible for premature deliveries in four cases, leading top post partum death of two infants. Source identification was inconclusive, no further outbreaks have occurred since the reported endemic occurrence. Dangers of nosocomial infections in patients with intravenous tokolysis are discussed. PMID- 2264413 TI - [Fatal outcome in HELLP syndrome]. AB - The patient was a 32-year-old para 2 who developed within a few hours after the first symptoms a lethal HELLP-syndrome. Despite initially normal blood pressure an hepatic failure, hemolysis and cerebral bleeding appeared. The autopsy revealed an eclamptic liver and symptoms of a disseminated intravasal coagulation (DIC). As a consequence a quick delivery instead of a conservative-expectant management because of fetal prematurity is recommended. PMID- 2264414 TI - [Intensive care aspects in eclampsia with multiple organ failure]. AB - Because of a good prenatal care eclampsia has been very seldom. But it is still a severe disease. By means of a case report vital symptoms and possible etiologic mechanisms are discussed. The meaning of an interdisciplinary intensive care and a subtle monitoring has been emphasized. PMID- 2264415 TI - [Questions to the editors. Preoperative diagnosis before hysterectomy]. PMID- 2264416 TI - [Chlamydia--screening at the end of pregnancy?]. PMID- 2264418 TI - [Diagnosis and therapy of fibrocystic breast disease]. AB - Fibrocystic disease (F.D.) can be observed in many women between 25 and 50 years. The typical histologic alterations in F.D. are often accompanied by estrogen dominance and relative hyperprolactinemia. For treatment local methods, diet, progesterones, danazol and the punction of large cyst are recommended. PMID- 2264417 TI - [Hormonal contraception and postmenopausal estrogen substitution in relation to malignant tumors]. AB - The concept of contraindication of estrogens in patients with endometrial, ovarian and cervical cancer has to be corrected. The German Society of Endocrinology recommend estrogens replacement in cervical, ovarian and vulva carcinoma. Breast and endometrial cancer are relative contraindications. Review of the literature with 104 citations. PMID- 2264419 TI - [Endocrinology and therapy of breast diseases]. AB - In 193 patients with fibrocystic breast diseases in 46% basal prolactin levels were elevated and many women had an increased reaction to TRH test with increased TSH and PRL serum levels. The author recommend for treatment progestogens dopamine antagonists and danazol. PMID- 2264420 TI - [Experiences with Rodazol therapy in the treatment of postmenopausal patients with metastatic breast cancer]. AB - 59 women with metastatic breast cancer in menopause were treated with 1 g/day aminoglutethimide and 3 mg/d dexamethasone. Only 4 patients had a objective remission, 17 women had a subjective improvement. Many patients had side effects. PMID- 2264421 TI - [Effect of 2 different forms of chemotherapy on remission in patients with advanced ovarian cancer]. AB - Results of combined treatment with two different drug combinations were compared in 82 patients with advanced ovarian carcinoma (stages III-IV). 41 patients received cyclophosphamide, methotrexate, vincristine (CMV) and the other 41 patients were treated with cyclophosphamide, adriamycin and cisplatin (CAP). 34 patients (82.9%) treated with the CAP-regimen and 20 patients (48.8%) treated with CMV had remissions following treatment. The average duration of remission was longer in the CAP group (18.1 months) compared to CMV treatment (11.6 months). The mean survival time 24.3 and 14.7 months respectively. It is concluded that three drug therapy is optimal in advanced ovarian carcinoma. PMID- 2264422 TI - [Comments on the survey in "Zentralblatt fur Gynakologie" 111 (1989) issue 20, p. 1390 on delivery of the second twin]. PMID- 2264423 TI - Influence of zinc deficiency on breaking strength of 3-week-old skin incisions in the rat. AB - The effect of dietary zinc deficiency on the breaking strength of abdominal skin incisions was studied in rats 21 days postoperatively. Zinc deficiency was induced with a low-zinc diet (1.4 mg zinc/kg diet) 14 days preoperatively. Thereafter serum zinc was reduced by 60%, but the zinc concentration in unwounded skin and liver remained similar to that of pair-fed controls given a zinc adequate diet (33 mg zinc/kg). The wound breaking strength (maximal load until wound disruption) was significantly lower in the zinc-deficient group (75% that of control wounds). The zinc concentration in wound tissue had decreased in the zinc-deficient group, but the wound hydroxyproline concentration was similar in the two groups. The results indicate that zinc is an important trace element during the early remodeling of scar tissue. PMID- 2264424 TI - Reversal of lethal citrate intoxication by intravenous infusion of calcium. An experimental study in pigs. AB - Intravenous infusions of 750 and 1000 ml 2.2% sodium citrate were given over a 60 min period to 17 pigs to study its effect on aortic pressure, electrocardiogram, ionised calcium, and citrate clearance. In group 1 (seven pigs) the animals did not receive calcium and the median survival time was 30 min (range 20-70 min). In groups 2 and 3 (five in each group) the pigs were treated with calcium chloride infusions (1 ml 10% calcium chloride to 10 ml citrate) and they all survived. In group 1 the ionised calcium concentrations in blood fell to values below 0.4 mmol/l, after which the blood pressure dropped abruptly. In the animals treated with calcium the mean ionised calcium concentration fell to 0.6 mmol/l, whereas total calcium increased to more than 7 mmol/l. The aortic pressure was consistently within normal values in the groups treated with calcium, but in the group that was not treated the blood pressure fell dramatically. There was no correlation between electrocardiographic changes and ionised calcium concentrations. In summary, calcium was an effective antidote to lethal citrate intoxication, and the only reliable method of determining the necessary dose of calcium was monitoring of ionised calcium concentrations. PMID- 2264425 TI - Endotoxin, epinephrine, glucagon, insulin and calcium ionophore A23187 modulation of pyruvate kinase activity in cultured rat hepatocytes. AB - Altered glucose metabolism is one of the commonly observed sequelae of sepsis and septic shock. The present investigation was undertaken to determine the role of endotoxin (ET) upon hepatocyte glucoregulation, by measuring the activity of pyruvate kinase (PK), a key glycolytic enzyme. Hepatocytes were exposed to endotoxin concentrations known to occur in vivo during sepsis, i.e., from 1 X 10( 14) to 1 X 10(-8) g/ml. The alteration of the enzyme activities after addition of epinephrine, glucagon, insulin and calcium ionophore A23187 with and without ET preincubation were also examined. ET alone decreased the PK activity by 12% at all concentrations tested. The basal inhibition of the enzyme caused by epinephrine (-48%) was partially blocked by ET preincubation above 1 X 10(-10) g/ml. There were no ET-(glucagon, calcium ionophore, insulin) interaction. These in vitro results do not support pyruvate kinase as a site of hepatic enzyme regulation defect in endotoxaemia. PMID- 2264426 TI - Severity and location of venous valvular insufficiency: the importance of distal valve function. AB - Venous calf pump function was evaluated with special reference to distribution and severity of deep venous reflux at different levels. A combination of ultrasonography, foot volumetry and venous plethysmography was used in 100 consecutive patients, 32 of whom were also studied with phlebography and intravenous pressure measurements. A clear relationship was found between clinical stage of chronic venous insufficiency and number of segments with reflux. Clinically important deep venous insufficiency was found particularly in patients with reflux in the distal posterior tibial veins, even in the presence of competent popliteal valves. The results demonstrated the calf pump to be functionally divided into a series of pumps, with the distal part more important than the proximal. The importance of evaluating venous valvular function at different levels for adequate assessment of venous calf pump function is emphasized. PMID- 2264428 TI - Intraabdominal abscess formation after major liver resection. AB - A series of 138 major liver resections undertaken between 1971 and 1987 were reviewed. Intrabdominal abscesses developed in 11 (8%) patients, a mean of 23 days (range 10-42) after operation and two died (mortality 18%). Eight developed after 63 right hepatectomies, two after 24 right lobectomies, one after 34 left hepatectomies and none after left lobectomies (17). Patients who developed intra abdominal abscesses underwent significantly longer operations (mean (SEM) 400 (48) compared with 275 (21) min) (p less than 0.05) and had significantly more bleeding during the operation (7,600 (1,750) compared with 3,200 (430), p less than 0.01) than those who did not. The amounts recovered from the abdominal drains, both before and after the diagnosis, were comparatively greater in patients with abdominal abscesses. Antibiotic prophylaxis was given to 10 of 11 patients who did and 89 of 127 patients who did not, form abscesses. We conclude that the risk of intra-abdominal abscess formation after major liver resection is increased: when a large amount of liver tissue is removed (right hepatectomy or lobectomy); when there is a lot of intraoperative bleeding; and when the operation takes a long time. Antibiotic prophylaxis did not affect the risk of abscess formation this series. PMID- 2264427 TI - Primary closure or secondary granulation after excision of pilonidal sinus? AB - Two methods for treatment of chronic pilonidal disease were compared in a randomised trial of 100 patients with a mean follow-up of 29 months. Four patients were excluded from the excision and closure group, leaving 96 patients for analysis. Initial primary healing was significantly more frequent after excision and primary closure (45/46; 98%) compared with excision and healing by secondary granulation (36/50; 72%). The mean healing time was significantly shorter in the excision and closure group (10.3 days) compared to the excision and granulation group (13 weeks). There was, however, no significant difference between the two groups in cure rate after the first operation. The recurrence rate in the excision and granulation group was 12% and after primary closure 20%. The presence of stiff hair and anaerobic bacteria were related to the failure of primary healing, but not associated with recurrence. Although the cure rate was the same regardless which operation was done, the primary healing was quicker and the healing time and duration of sick-leave were shorter after primary closure. Excision with primary closure therefore seems to be the preferable method. PMID- 2264429 TI - Evaluation of propranolol for prevention of recurrent bleeding from esophageal varices between sclerotherapy sessions. AB - Forty-one patients admitted with first episode of bleeding from esophageal varices were enrolled in a trial of the efficacy of oral propranolol to prevent rebleeding during the course of endoscopic sclerotherapy until obliteration. Single-blind randomization to sclerotherapy alone or with propranolol was used. At monthly endoscopy the varices were injected with 1% Aethoxysclerol until obliteration. If bleeding recurred, additional sclerotherapy was given. There was no intergroup difference in time to eradication of varices (8.1 vs. 7.7 months). The cumulative number of bleedings from varices and from distal esophageal ulcerations was identical in the two study groups. Five patients in the control group but only one in the propranolol group died of bleeding in the study period, a difference of only borderline significance (chi 2 = 4.08, df = 1). There were no specific side effects of propranolol. Thus propranolol did not significantly reduce the frequency of rebleeding until variceal obliteration, but could have had some influence on the gravity of rebleeding. PMID- 2264430 TI - Influence of malnutrition on regeneration and composition of the liver in rats. AB - Using a new experimental model of protein-calorie starvation, the impact of malnutrition on liver regeneration, and the changes in liver composition during malnutrition and regeneration, were studied. Forty-one rats were allocated to one of 3 groups: group I (n = 13) were normally nourished rats which underwent partial hepatectomy, group II (n = 16) were semistarved rats which underwent partial hepatectomy, and group III (n = 12) were normally nourished rats which underwent sham operations. Liver biopsy specimens were taken at the time of partial hepatectomy and when the rats were killed after 48 hours of regeneration. The samples were used for determination of water, fat, glycogen, protein, DNA, and RNA content. The replication rate of liver cells was measured by autoradiography after continuous incorporation of tritium labelled thymidine. Malnutrition was associated with a higher postoperative mortality and a reduced rate of regeneration. The livers changed during malnutrition with a reduction in both size and glycogen concentration. After 48 hours of regeneration there was a marked change in liver composition with severe fatty degeneration, a fall in glycogen and a rise in water content. RNA concentration was stimulated during regeneration, but during malnutrition the protein content decreased. The results emphasise the importance of an adequate nutritional state for liver regeneration. PMID- 2264431 TI - Anal spinchter reconstruction. Surgical results and functional outcome. AB - Direct repair of anal sphincter injuries was undertaken in seven patients, three men and four women. Obstetrical tears were the cause of injury in all the female patients; surgical trauma, road traffic accident, and sexual assault caused the injuries to the men. Temporary covering colostomies were fashioned for six patients either before, or at the time of, the repair. There were no major complications associated either with the repairs or with the colostomy closures. The degree of incontinence was reduced in all patients, but only two became completely continent after the operation. The change in anal sphincter pressures was not significant. Postanal repair was subsequently undertaken for one woman, but all the other patients were satisfied with their repairs. We conclude that direct sphincter repair should be the treatment of choice for patients with major injury to the anal sphinchter. PMID- 2264432 TI - Malignant intestinal schwannoma. Case report. AB - Malignant schwannoma of the small intestine is rare and diagnosis often late. Histologic distinction from fibrosarcoma and leiomyosarcoma may require electron microscopy. The primary treatment is surgical. Close postoperative observation is recommended because of the tendency to recurrence. Remission after chemotherapy has been reported, but without controlled studies. The 5-year survival rate is unknown. Two cases are presented. PMID- 2264434 TI - Vocal cord paralysis caused by a cyst in extraglandular thyroid tissue. Case report. AB - A 37-year-old woman presented with hoarseness two days after developing pain while undergoing physiotherapy for tension in her neck. Computed tomography showed a probably benign mass near to the left lobe of the thyroid, which was found at operation to be attached to the recurrent laryngeal nerve. The nerve was dissected free, the tumour removed, and the patient and her voice recovered fully. Histological examination confirmed a benign cyst in extraglandular thyroid tissue and the patient is well two years later. PMID- 2264433 TI - Mediastinal chondrosarcoma. Case report. AB - A 34-year-old man and a 71-year-old woman underwent radical removal of mediastinally sited chondrosarcoma, presumably originating in the periosteum of the vertebral body. The man (with mesenchymal chondrosarcoma) died of remote metastasis 6 years postoperatively. The woman (poorly differentiated chondrosarcoma, grade 2-3) is still alive 2 years after the operation. PMID- 2264435 TI - Spontaneous rupture of the liver associated with pregnancy. Case report. AB - A 28-year-old woman, gravida 1, para 0, presented with toxemia, abruptio placenta and disseminated intravascular coagulopathy. Rupture of the liver with hypotension and oliguria occurred 36 hours after a stillbirth. The patient died of multiple organ failure 9 days after delivery. PMID- 2264436 TI - Continuous assessment of oxygen saturation and subcutaneous oxygen tension after abdominal operations. AB - Ten patients undergoing abdominal operations had oxygen saturation (SpO2) and transcutaneous (PtcO2) and subcutaneous (PscO2) oxygen tensions monitored continuously during the second and third postoperative nights from 11 pm to 7 am. At the end of the second postoperative night an oxygen stimulation test (10 l/min by face mask) was carried out in eight of the 10. Median SpO2 was 91% (range 82 95) on the second, and 91% (86-95) on the third, postoperative nights, respectively. Six patients had intermittent episodes of desaturation to less than 80%, each of less than one minute's duration. PtcO2, but not PscO2, followed the episodic variations in SpO2. PscO2 was 58 mmHg (46-69) on the second postoperative night and 61 mmHg (48-71) on the third postoperative night. PscO2 correlated with SpO2 in all but one patient who had lower PscO2 than expected from the measured SpO2 and estimated PaO2. Oxygen treatment increased individual PscO2 by 14 mmHg (9-49), PtcO2 by 38 mmHg (10-104), and SpO2 to 99% (95-100), but stable PscO2 was not achieved within the 20 minute period of treatment. These results obtained during continuous measurements show pronounced intersubject differences in oxygen tensions near the surgical wound in the late postoperative period. The results suggest that pulmonary oxygenation is the most important determinant of mean subcutaneous oxygen tension after uncomplicated elective abdominal operations. PMID- 2264437 TI - Delaying factors in primary treatment of breast cancer. AB - An effort has been made to study possible delaying factors in the diagnosis and primary treatment of breast cancer. The data are based on 273 female patients, referred to the Department of Oncology, Lund, constituting 50% of all primary breast carcinomas without a previous malignancy diagnosed in 1986 in a catchment area of 1.2 million. Of these, 68% initially consulted a general or private practitioner, whereas only 21% directly consulted surgical departments. The interval from the initial consultation to operation, analysed multivariately, was correlated to the number of referral-steps (13 vs. 75 days), the category of physician initially consulted (15 vs. 33 days), and the outcome of a combined positive or negative mammography + aspiration cytology (13 vs. 58 days). If one or both of these diagnostic procedures were negative, the delay varied considerably between the four categories of physicians initially consulted. The median time between decision and start of radiotherapy was 38 days, constituting 46% of the time from the initial consultation to start of this treatment modality. PMID- 2264438 TI - Lower-limb oedema after thromboembolectomy for acute arterial occlusion. AB - To establish the degree of oedema after thromboembolectomy ad modum Fogarty, leg volume changes were recorded daily in 56 patients. Significant increase was found in the volume of the ipsilateral leg, maximally 12.9 +/- 12% after c. 1 week. The swelling was significantly greater if the popliteal artery had been explored than if it had not. The volume increase was weakly correlated to the duration of ischaemia, but this could be explained by higher incidence of below-knee incisions in patients with longer preoperative ischaemia. Compartment syndrome occurred in one case. The outcome of the operation correlated to leg volume changes on postoperative day 1, but not significantly to the maximal volume increase. It is suggested that the early volume changes represent increased microvascular permeability, and that to this relatively modest oedema is in some cases later added more severe swelling due to impairment of the lymphatic outflow. PMID- 2264439 TI - Preliminary results for the repair of difficult recurrent inguinal hernias using expanded PTFE patch. AB - The repair of recurrent inguinal hernias can be a complex problem. This study examines the results of 52 difficult recurrent inguinal hernias repaired with an expanded PTFE patch. Patients were selected because the hernia had either multiple defects, a single large defect that could only be repaired with excessive tension, or the surrounding tissues were unable to support a sutured repair. The number of previous hernia repairs ranged from 1 to 7 with a mean of 2.5 repairs. Hernias recurred in 5 patients (10%) after a mean follow up of almost 2 years. Three of these recurrences were inguinal, around the patch, and 2 were through the femoral canal. There was no association between postoperative wound complications and hernia recurrence. PMID- 2264440 TI - Early detection of gastrointestinal mucosal ischemia in porcine E. coli sepsis. AB - The aim of this study was to investigate the oxygenation of the gastrointestinal tract mucosa using indirect pH measurements in a porcine septic model (intravenous infusion of live E. coli). By means of intraluminally placed balloon catheters (Tonomitior) permeable to CO2, intramucosal pH (pHi) was calculated using the Henderson-Hasselbalch equation. Cardiopulmonary hemodynamics and portal blood flow were measured using Swan-Ganz catheters. Samples were taken from the gastrointestinal tract for histological examination. Nine pigs were given i.v. E. coli infusion while six pigs served as sham controls and were given an equivalent amount of Ringer's solution only. All septic animals developed hemodynamic signs of septic shock. Gastric, small intestinal and sigmoid colonic pHi decreased gradually during the four hour observation period. In the small intestine and the sigmoid colon the decrease was significant already after one hour (p less than 0.01 and p less than 0.02, respectively). Microscopic examination of tissue specimens obtained 4 hours following induction of sepsis revealed normal or close to normal findings in all the sham and in more than half of the septic animals. These findings indicate that abnormally low gastrointestinal intramucosal pH may be found early in septicemia, preceding microscopically detectable damage by several hours. It is concluded that the tonometer technique does provide early detection of gastrointestinal ischemia in septic shock. PMID- 2264441 TI - Recurrent ulceration after proximal gastric vagotomy. Possible role of mucosal barrier. AB - Between 1971 and 1986 532 proximal gastric vagotomies were carried out at the Pelgulinna Hospital. The five-year recurrence rate was 5.5% (n = 29). We have studied 40 patients with chronic duodenal ulceration, 20 patients who had effective proximal gastric vagotomy, and seven patients who presented with recurrent ulcers after proximal gastric vagotomy. Patients who had positive Hollander tests after vagotomy, and those with disorders of gastric motility, were excluded. In the group with recurrent ulcers the concentration of neutral mucopolysaccharides in the gastric juice was significantly lower than in the other two groups, and it correlated with the amount of material showing a positive reaction to periodic acid Schiff (PAS) in the gastric mucosa. This group also had significantly higher mean serum gastrin concentrations and mast cell degranulation rates in the mucosa of the fundus and the antrum. We conclude that qualitative changes in the production of gastric mucus lead to defective functioning of the mucosal barrier in patients with recurrent ulcers and may be one of the causes of recurrences. PMID- 2264442 TI - Early endoscopic fibrin sealing of high-output postoperative enterocutaneous fistulas. AB - In seven patients with high-volume enterocutaneous fistula following gastric surgery, a new method of treatment was used. Fibrin tissue adhesive was applied transintestinally under endoscopic guidance, in one or multiple sessions, to occlude the anastomotic dehiscence and the perianastomotic cavity. Fistula output diminished rapidly in all cases, and complete closure was endoscopically confirmed. There were no complications related to the method. Because of the simplicity and safety of this procedure compared with the complexity of surgical treatment and the persistently high mortality associated with conservative management, interventional endoscopic approach is suggested as an option for treatment of high-volume alimentary fistula. PMID- 2264443 TI - Volvulus of the caecum. An evaluation of various surgical procedures. AB - To evaluate the various operations for caecal volvulus we reviewed 48 patients who were treated between 1948 and 1989. Six were treated conservatively (the volvulus resolved before operation), and the remaining 42 patients (43 operations) were treated by untwisting (n = 14, 2 early deaths); caecopexy (n = 13, no deaths); caecostomy (n = 3, 2 early deaths); or resection (n = 13, one early death). At follow up a mean of 11.8 years later (range 0.4 to 34) the numbers of patients who had remained free of symptoms were 6, 5, 1 and 9, respectively. We conclude that resection gives the best long term results with acceptable mortality and morbidity and should be the treatment of choice for caecal volvulus. PMID- 2264444 TI - Restoration of continuity of the large intestine with the premium CEEA stapler: a new aseptic method. Surgical technique. AB - Ten patients had their large bowel continuity restored (5 after Hartmann resection and 5 after defunctioning left colostomy) by an improved, essentially aseptic, stapling technique with the premium CEEA stapler. There were no deaths and no complications. PMID- 2264445 TI - Low anterior resection with double stapling technique. Surgical technique. PMID- 2264446 TI - Stapled coloanal anastomosis after linear closure of everted anorectal stump. Surgical technique. PMID- 2264447 TI - Axillary artery rupture complicating anterior dislocation of the shoulder. Case report. AB - Vascular injury is a rare complication of anterior dislocation of the shoulder joint. Two cases, both in elderly persons (65 and 74 years) were treated in our Department during a 5-year period. Atherosclerotic changes of the axillary artery and previous shoulder dislocation are predisposing factors for such injury. PMID- 2264448 TI - Fatal duodenocaval fistula resulting from a giant peptic ulcer. Case report. AB - Duodenocaval fistula is exceedingly rare. Penetrating trauma, gunshot wounds and toothpick perforation of the duodenum are known aetiological factors. Two recent case reports have implicated radiation-induced ulceration of the duodenum. We describe the first case of duodenocaval fistula resulting from a giant peptic ulcer of the descending duodenum. PMID- 2264449 TI - Necrosis of the femoral heads following aorto-bifemoral vascular grafting. Case report. AB - A case of bilateral necrosis of the femoral head, following aorto-bifemoral vascular bypass, is reported. The necrosis of the femoral heads might be explained by a temporary obstruction of the lateral blood supply peripheral to the arteria profunda femoris, due to an increased joint pressure caused by regional oedema with joint effusion and swelling of the joint capsule. PMID- 2264450 TI - Ectopic spleen in the retroperitoneum. Case report. AB - A 43-year-old man presented with a retroperitoneal mass, the histological examination of which showed well developed spleen parenchyma with a capsule and fibrous tissue in between normal looking splenic cells. Postoperative 99mTc sulphur colloid scans of his liver and spleen were normal. This is, to our knowledge, the first reported case of an ectopic spleen in the left retroperitoneal space. PMID- 2264451 TI - Transrectal ultrasound-guided biopsy for verification of lymph-node metastasis in rectal cancer. Case report. AB - Mesorectal lymph-node involvement in rectal cancer may be detected by endosonography as a hypoechoic lesion, but false positives are a problem. We report a new method, using transrectal ultrasound-guided core biopsy, for verifying metastatic growth in a mesorectal lymph node detected by endosonography at postoperative follow-up for low rectal cancer. PMID- 2264452 TI - Effect of listeria infection on the allotransplantation reaction in cyclosporin A treated mice. AB - Allogeneic reaction of listeria-infected Balb/c mice to C3H skin graft was examined. The recipients were infected with Listeria innocua and treated with Cyclosporin A. Listeria infection in the treated mice enhanced skin rejection reaction reduced by the immunosuppressor. PMID- 2264453 TI - Identification of species of the Genus listeria by fermentation of carbohydrates and enzymatic patterns. AB - Patterns of carbohydrates and determination of API ZYM and API oxidases can be considered a useful way to differentiate the strains of Listeria. With all this information it is possible to work out a schematic table that allows the identification of Listeria strains with a remarkable certainty. By numerical analysis four differentiated clusters have been demonstrated. PMID- 2264454 TI - The distribution of vesicular-arbuscular mycorrhizal fungi in India. AB - Vesicular-arbuscular mycorrhizal fungi are widely distributed throughout the area studied including different altitudes ranging from sea level to 2500 ft above sea level. VAM fungi were recorded from 88% of the sites examined with Glomus fasciculatum and Glomus macrocarpum being the most commonly recorded. Mean species diversity was found to be maximum in the areas thickly vegetated and undisturbed. PMID- 2264455 TI - The course of LCMV infection in gnotobiotic and conventional adult mice pretreated with attenuated NDV vaccine. AB - A single intraperitoneal treatment with two different doses of live Newcastle Disease Virus (NDV) containing attenuated NDV vaccine one day before intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV) had no influence on the ratio and time of deaths after infection with a 100 LD50 dose of LCMV either in gnotobiotic or in conventional mice. There was no difference either in the LD50 values determined on the basis of three parallel LCMV titration performed on mice pretreated with two different doses of vaccine or untreated. NDV vaccine pretreatment thus did not influence the cellular immune response to LCMV infection either in gnotobiotic or in conventional adult mice. As the NDV vaccine increased the cellular immune response to LCMV infection in suckling mice according to earlier results, the present results reinforce our earlier statement that the direction of immunomodulatory effects can be influenced by age. PMID- 2264456 TI - Citric acid production with mixed strains of Aspergillus niger in submerged culture. AB - Citric acid yield of 8 different strains of Aspergillus niger in pure and mixed cultures was investigated. The yield varied remarkably with the strain and combination of strains. Generally, the yield of citric acid for a given strain was higher in pure than in mixed culture. However, low yielding strains in combination often augmented the yield under mixed culture. The possibility of an additive genic effect is discussed. PMID- 2264457 TI - Monocytosis producing activity from virulent and avirulent strains of Listeria. AB - Monocytosis is a hallmark of listeriosis in many species. A similar phenomenon is induced by a monocytosis-producing activity (MPA) purified from the organism. The relationship between MPA production and virulence is unclear. The purpose of this study was to measure MPA in extracts prepared from strains with known degrees of virulence and haemolysin production. Differential leukocyte counts on peripheral blood cells were performed 24, 48 and 72 h after injection of 0.5 mg MPA. In the strains we tested those known to be virulent produced monocytosis; those which were avirulent did not. PMID- 2264458 TI - Comment on the composition of soy protein based infant and follow-up formulas. ESPGAN Committee on Nutrition. PMID- 2264459 TI - Oxygen toxicity in the neonatal period. AB - Oxygen is toxic because it produces oxygen radicals. One important oxygen radical generating system is hypoxanthine-xanthine oxidase. Hypoxic newborn babies who have elevated concentrations of hypoxanthine in tissues and body fluids and simultaneously are treated with supplementary oxygen, may therefore produce oxygen radicals in excess overwhelming the body's natural defence systems against free radicals. Further, the capacity of many of these defence systems are probably reduced in the preterm baby. A series of conditions in neonates may, at least partly, be caused by oxygen radicals, e.g. bronchopulmonary dysplasia, retinopathy of prematurity, necrotising enterocolitis and patent ductus arteriosus. These conditions may be different facets of one disease; the "Oxygen radical disease in neonatology". It is speculated that oxygen radicals play a role in regulating the perinatal circulation. This new insight concerning the role of oxygen radicals may have fundamental consequences for treatment and handling of sick newborn babies. PMID- 2264460 TI - The effect of a warm environment on respiratory water loss in fullterm newborn infants on their first day after birth. AB - Continuous measurements of respiratory water loss (RWL), oxygen consumption and carbon dioxide production were made in 21 fullterm infants on their first day after birth. The infants were first studied in incubators with a temperature of 32.5 degrees C and an ambient humidity of 50%. After an interval with stable conditions the incubator temperature was raised to 36.5 degrees C while the water vapour pressure was kept constant. When the rectal temperature had increased to 37.8 degrees C or when the infant had started to sweat, the relative humidity in the incubator was increased to 50%. At the start of the measurements mean RWL was 4.9 mg/kg min. On the average, RWL increased to a maximal value of 7.0 mg/kg min in the warm environment. Mean oxygen consumption only increased from 5.3 to 5.8 ml/kg min. This meant that when nursed in this warm environment the infants were able to increase their respiratory water loss by nearly 50% without a significant change in oxygen consumption. PMID- 2264461 TI - Bioavailability of urea nitrogen for the low birthweight infant. AB - Previous studies have demonstrated increased retention (40%) of dietary urea nitrogen by term infants recovering from infection compared to healthy infants (13%), possibly due to a higher requirement for nitrogen. Since low birthweight infants also have a high requirement for nitrogen, the bioavailability of urea nitrogen was investigated in low birthweight infants using 15N,15N-urea. Four low birthweight infants (gestational age = 30 +/- 2.2 weeks [mean +/- SD], birthweight = 1.4 +/- 0.3 kg) were fed formula enriched with 15N,15N-urea. Metabolic balance studies (72 hours) were performed with urine and fecal collections. Nitrogen was quantitated by Kjeldahl analysis and 15N,15N-urea by gas chromatography/mass spectrometry. Mean nitrogen intake was 489 +/- 32 mg/kg/d, with 75% nitrogen absorption and 62% nitrogen retention. Maximum urinary enrichment was 8%. Cumulative 15N,15N-urea excretion was 72%, resulting in 28% retention. Thus the bioavailability of urea nitrogen for low birthweight infants appears to be intermediate between compromised and normal term infants. PMID- 2264462 TI - Retinopathy of prematurity. Where to set screening limits? Recommendations based on two Danish surveys. AB - If all cases of serious ROP are to be detected, followed, and possibly treated, and the entire natural history of ROP to be recognized, screening limits should be set at no lower than gestational age 32 weeks and/or birthweight 1,750 g. These recommendations are based on the experience gained from two Danish surveys: cases registered as visually impaired (compulsory), from the whole country, covering the birth years 1971-88 (n = 142), and an epidemiological study from a Danish county comprising 411 infants considered at risk in 1982-1987; 63 infants developed ROP, eventually resulting in blindness in 6 of them. PMID- 2264463 TI - The impact of gluten on haematological status, dietary intakes of haemopoietic nutrients and vitamin B12 and folic acid absorption in children with coeliac disease. AB - The haematological status, as well as the fractional absorptions of folic acid and of vitamin B12 (FAFol and FAB12) were studied longitudinally in 20 coelic children aged 1.2-16.6 yr (mean 7.5 yr) during periods of gluten-free and gluten containing diets. The absorption methods were specially adapted to use in children, and age-related reference limits were established. Also, dietary intakes of iron, folate and B12 were registered. The haemoglobin concentrations did not show any significant differences in relation to shifts in diet. A few had mild anaemia while the haemoglobin concentrations in the other patients remained within normal range. The iron status, as judged from mean corpuscular volume (MCV), serum (S)-iron, S-transferrin and saturation %, appeared to be generally insufficient. However, the only significant change related to shifts in diet was an increase of S-iron during the first period of gluten-free diet. Dietary intakes of iron proved to be insufficient, regardless of the type of diet. Plasma (P)-B12 concentrations demonstrated a wide range of values above the lower normal limit, whereas the level in a single patient was within the "intermediate range" of B12 insufficiency (150-200 pmol/l). The folate status (erythrocyte-folate) showed significant variations related to dietary changes. However, few patients were folate depleted. FAFol and FAB12 demonstrated rapidly occurring, and significant decreases and increases in relation to gluten challenge and gluten free diet, respectively. Bacterial overgrowth of the small intestinal tract was not found to be a plausible cause of the B12 malabsorption in the case of 5 patients observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264464 TI - Greek immigrant children in southern Sweden in comparison with Greek and Swedish children. II. Meal pattern and food habits. AB - Greek immigrant children (GI) belonging to the second generation of immigrants in Sweden have been compared with Swedish children (S) and Greek children in Greece (G) regarding meal pattern and food habits. Interviews were performed in the homes. Meal pattern and frequency of consumption of various food items were studied by 24-hour recalls, and the food frequency interview method. The meal pattern and the distribution of meals and snacks during the day did not show large differences between the groups. In the GI and G groups it was common to start the day with milk and sugar. The same habit was reported before going to bed. It was common in the GI and G groups to have a prepared meal (dinner) relatively late in the evening. Of the S children only 55% had dinner. GI children had a less frequent intake of vegetables compared to S and G children. GI and G children were heavy consumers of sweets and snacks. In conclusion, the Greek immigrant group had food habits similar to those of Greek rural children with few distinctive exceptions. Greek immigrant families had no difficulties in preparing Greek food. PMID- 2264465 TI - Serum carnitine level in phenylketonuric children under dietary control in Greece. AB - Although total, free and esterified carnitine blood levels were found to be low (p less than 0.001) in phenylketonuric patients under dietary treatment compared to controls, no clinical signs of carnitine deficiency were noticed. Exclusion from the PKU diet of nutrients rich in carnitine has been suggested. Supplementation of the diets with carnitine or preferably enrichment of the PKU formulas with carnitine will rectify the restriction of extrinsic carnitine in PKU dietary treatment. PMID- 2264466 TI - Use of a test diet in screening for neuroblastoma reduces false-positives attributable to food intake. AB - We attempted to reduce false-positives during screening for neuroblastoma using a qualitative urine test by introducing a test diet without foodstuffs known to cause false-positive results. In preliminary in-vivo experiments, intake of contra-indicated foods such as orange juice or banana was shown to result in high percentages of false-positive results several hours after food intake. False positive results were obtained even after 24 hours among breast-fed infants whose mothers received orange juice. In a controlled field trial the false-positive rate was reduced to 2.84% among 540 infants taking the test diet compared with 5.05% among 9,844 control infants following conventional guidance on contra indicated foods (p less than 0.05). For comparison, a questionnaire survey of nationwide screening in Japan in 1987 revealed that 66% of the screening centres employed qualitative urine tests, either a Spot or Dip method. False-positive rates, including those due to inappropriate urine collection, ranged from 0.4% to 33.7% (mean 7.1%). Rates ranged from 0.2% to 18.7% (mean 3.4%) in the remaining 34% of screening centres employing a quantitative method with high performance liquid chromatography. PMID- 2264467 TI - Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy. AB - We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n = 20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n = 36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whom were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m2/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. PMID- 2264468 TI - Child sexual abuse. PMID- 2264469 TI - Is IgE in umbilical cord blood really predictive? PMID- 2264470 TI - Transient hypogammaglobulinemia of infancy. PMID- 2264471 TI - Principles of growth standards. PMID- 2264472 TI - Nephrocalcinosis and phosphate supplementation in a preterm infant. PMID- 2264473 TI - Predictive value of IgE levels in infancy. PMID- 2264474 TI - Effect of physiotherapy in asthmatic children--a one-year follow-up after physical training once a week. PMID- 2264475 TI - Prophylaxis and therapy of glomerulonephritis in the course of anaphylactoid purpura. The results of a polycentric clinical trial. PMID- 2264476 TI - Early introduction of uncooked cornstarch for the treatment of glycogen storage disease type I. PMID- 2264477 TI - Incidence and prevalence of coeliac disease in Tampere. Coeliac disease is not disappearing. PMID- 2264478 TI - Marrow hypoplasia associated with congenital neurologic anomalies in two siblings. AB - Two siblings with congenital neurologic structural anomalies and delayed-onset selective bone marrow hypoplasia in a previously undescribed constellation of symptoms are presented. Differences between these cases and other well known syndromes are discussed. The importance of this association is the implication that children with congenital neurologic abnormalities may be at increased risk for the development of hypoplastic hematopoietic conditions. PMID- 2264479 TI - Cardiac myxoma as the cause of death in an infant. AB - Cardiac myxoma is a rare disease most frequently encountered in adults, usually localized in the left atrium. It rarely occurs in infants. We report a 3 1/2 month old girl whose sudden death was caused by a large atrial myxoma, completely occluding the tricuspidal orifice. The importance of possible prodromal symptoms suggesting a cardiac disease is stated, and the role of echocardiography as an excellent examination technique is discussed. PMID- 2264480 TI - Renal tubular acidosis in childhood. AB - Nineteen children with clinical diagnoses of renal tubular acidosis were followed for periods ranging from 3 months to 20 years. Twelve patients had Type 1 renal tubular acidosis, five had Type 2, and two had Type 4. No sex predilection was found for any one of the types. Most patients had been diagnosed before 18 months of age, with failure to thrive the most common presentation. Tachypnea, polydipsia, polyuria, and vomiting were frequent symptoms. Some of these children had associated renal hypoplasia, vesicoureteral reflux, unilateral renal agenesis, glomerulocystic disease, adult polycystic kidney disease, and cyanotic congenital heart disease. Urinary anion gap may be useful for differential diagnosis of altered distal urinary acidification from other hyperchloremic metabolic acidosis. Furosemide test may need further investigation. Inability to raise urine to blood pCO2 gradient is helpful for diagnosis of Type 1 renal tubular acidosis. Hypokalemia, hypocalcemia, hypophosphatemia, decreased tubular reabsorption of phosphate, and hypercalciuria occurred in some patients. Complications included rickets in two, nephrocalcinosis in one, and episodic hematuria in one. There was relative bicarbonate wasting in children with Type 1 renal tubular acidosis, with a mean therapeutic bicarbonate requirement of 4.4 +/ 2.6 meq/kg/day. The mean bicarbonate dose for patients with Type 2 renal tubular acidosis was 8.3 +/- 2.6 meq/kg/day. Most children had good response to treatment with complete catch-up linear growth in 13, improved growth in 4, and continuing poor growth in 2. Two patients died during follow-up. Two other patients maintained normal growth without medication. PMID- 2264481 TI - Clinical observation of meconium peritonitis. AB - Twenty cases of meconium peritonitis were found between September 1980 and March 1988 at Mackay Memorial Hospital. The male to female ratio was 1.5 to 1. Six of the 20 cases involved premature babies. The great majority presented symptoms and signs before 5 days old, but one case was not diagnosed until 13 months of age. Polyhydramnios of the mother was found in six cases (30%). Abdominal distension was the universal symptom in all 20 cases. Hydrocele was noticed in 8 of the 12 male babies. In seven cases (35%) radiological examination showed abdominal calcifications. All patients underwent surgical intervention. Peritonitis was of cystic type in seven cases (35%); fibroadhesive in nine cases (45%); generalized in four cases (20%). Evident intestinal perforation was noted in 13 patients, and a mechanical obstructive lesion was found in 9 cases (45%) including intestinal diaphragm, atresia, volvulus, and Hirschsprung's disease. In only two patients (10%) was neither evident perforation nor obstructive lesion. The overall mortality rate was 30% (6/20), with no mortality after 1986 (0/6). The mortality seemed increased in those associated with perforation (4/13) and midgut volvulus (2/2) in particular, compared with non-perforation cases (1/7). It appears that early aggressive operation, and meticulous postoperative care, have contributed to the higher survival rate in recent years. PMID- 2264482 TI - Assessment of ventricular septal defect by echocardiography. AB - Both 2-D echocardiography and angiocardiography were performed preoperatively in 40 children with isolated ventricular septal defect (VSD). The diagnosis of VSD was confirmed and the size of VSD was measured during operation within on month of the study. There were 27 males and 13 females (age: 10mos-9 yrs). The VSD was classified into perimembranous type (24), supracristal type (14), and AV canal type (2) by surgery. The maximal VSD areas were calculated by 1/4 pi De2 (De = maximal defect diameter measured by 2D echo). The maximal shunt flow areas were measured by color Doppler echocardiography from frame by frame search of the video tape. The maximal shunt flow area was corrected by the body surface area to be the maximal shunt flow area index. A left ventriculogram (LVG) was performed from 4-chamber and left lateral views to measure the maximal diameter of the defect. The maximal defect area of VSD on angiocardiogram was also calculated by 1/4 pi Da2 (Da = maximal defect diameter measured by angiocardiography). The VSD areas measured by different methods were compared by the linear regression analysis. We found that: (1) there is good correlation of the maximal defect diameter and the area of ventricular septal defect by 2-DE and LVG (r = 0.80, p less than 0.0001 v.s. r = 0.78, p less than 0.0001). (2) the ventricular septal defect area by 2-DE had a better correlation with the surgical measurement than that by LVG (r = 0.93, p less than 0.0001, v.s. r = 0.80, p less than 0.0001). (3) the size of ventricular septal defect measured by two-dimensional echocardiography has a better correlation with the MSFAI than the LVG did (r = 0.81, p less than 0.0001, v.s. r = 0.64, p less than 0.0001). Therefore, by measuring the maximal defect diameter, maximal defect area and maximal shunt flow area index, the echocardiography can provide an accurate and non-invasive assessment of isolated VSD in children. PMID- 2264483 TI - [Congenital megacalyces]. AB - Congenital megacalyces is a calyceal anomaly characterized by nonobstructive dilatations of the calyces, associated with hypoplasia of the medullary pyramids. In the past three years, seven patients with congenital megacalyces were found incidentally during renal ultrasonic examination. There were five boys and two girls who were asymptomatic, except for a case with hematuria. Three cases presented bilateral and four unilateral, ages ranged from 7 to 14 years. In this series, all cases with dilatations of the calyces were initially detected by sonography, and then confirmed by other radiologic examinations. On intravenous urography, contrast material was visible at the normal time, but prolonged opacification. The radiological features presented widen calyces, flattened papillae, absence of papillary tips and usually no significant dilatation of the renal pelvis and ureter. The renal medulla had become thin. An ultrasound examination showed the kidneys with dilated calyces and decreased parenchyma. Renal pelvis and ureter were mostly normal in size. Diuretic radionuclide renogram T1/2 was performed in five cases, to disclose nonobstructive lesions. Radionuclide cystography, underwent in three cases, revealed no reflux phenomenon. Renal function was normal in all cases. Congenital megacalyces are a non-progressive lesions. Therefore, it is important to recognize the clinical entity and avoid unnecessary surgery. Since sonography is a noninvasive modality, it can serve as a tool for long-term follow-up of these patients and for the detection of possible future stone formation. PMID- 2264484 TI - 45,XO/46,XY in a newborn with the stigmata of Turner syndrome: report of one case. AB - A newborn with ambiguous external genitalia and the stigmata of Turner syndrome presented with the following features: short stature, hypertelorism, bilateral epicanthal folds, ptosis, low-set ears with prominent auricles, high-arched palate, low posterior hairline, webbed neck, broad and short chest, widely-spaced and hypoplastic nipples and clitoris-like phallus with hypospasdias. He also had patent ductus arteriosus, the secundum type of atrial septal defect and mitral stenosis. Chromosomes of peripheral blood showed mosaicism of cells with 45,XO/46,XY. An exploratory laparotomy was performed at five months of age. The right side ovotestis-like gonad was removed. The left side gonad in the scrotum was normal. No pathological gonadoblastoma was found. PMID- 2264485 TI - Neonatal morphine withdrawal syndrome: report of two cases. AB - Two siblings born to a morphine-addicted mother with morphine withdrawal syndrome were reported. The first child, a female, presented with irritability, jitteriness and watery diarrhea at three days of age. The second, a male, presented with jitteriness and irritability when twelve hours old. Both cases were managed with supportive care; phenobarbital was given for the first case. These two cases and the literature concerning neonatal morphine withdrawal syndrome are reviewed. PMID- 2264486 TI - [Wilson disease presenting as fulminant hepatic failure, acute hemolytic anemia and renal failure: report of one case]. AB - Wilson disease presenting as fulminant hepatic failure, severe hemolysis and renal failure is rare in the literature. A ten-year-old boy--complaining of abdominal pain, jaundice, tea-colored urine, and anemia was admitted to this hospital; examination showed Kayser-Fleischer rings, anemia associated with hemolysis, mildly elevated serum transaminases, extremely elevated bilirubin levels, low serum ceruloplasmin level, slightly elevated serum copper, excessive 24-hour urine copper excretion, and severe renal function insufficiencies. Under the impression of Wilson disease with fulminant hepatic failure, the patient was treated by oral D-penicillamine 1 gm per day, intravenous zinc sulphate (about 8 mg per day elemental zinc), and given other supportive treatment. Unfortunately, the patient died of hepatic failure complicated with septic shock 21 days after the onset of symptoms. Autopsy found liver copper content was 586.92 ug/gm dry weight and kidney copper content: 300.19 ug/gm dry weight, abnormally high as compared with normal tissue. A review of the literature led to conclusion that the best treatment for Wilson fulminant hepatic failure is liver transplantation. PMID- 2264487 TI - [Obstructive uropathy in genital prolapse]. AB - Two cases of genitourinary prolapse are presented, with a severe high obstructive uropathy complicated with lithiasis and infectious picture. Both cases were elderly patients and had had this problem for many years. They had received no urological or gynaecological examination that could have prevented later complications. As presentation frequency of this pathology is scarce, which undoubtedly is an index of health care, we have reviewed the existing literature to confirm the few descriptions currently reported. Incidence, different etiopathogenic theories explaining this picture, distinctive radiological data and treatment are analyzed. PMID- 2264488 TI - [Endoscopic treatment of congenital vesico-ureteral reflux]. AB - Sub uretric injection of teflon was used in 62 adults patients (92 ureteral units, 30 bilateral cases), 49 females, 13 males for treatment of congenital VUR, in 76 cases the refux was permanent. Degree (D) I = 18 Ureters (U), D II = 28 U., D III = 22 U., D IV = 7 U and D V = 1 U. Follow-up consisted in ultrasound examination cystogram and IVP performed at one month (92 U.) three months (81 U), one year (64 U) and two years (12 U). The procedure was performed under general anaesthesia. The quantity of polytef varied from 1 to 2 cc. Correction of VUR was observed in 70/92 U (76.1%), 11 persistent VUR were treated by reinjection of politef and in six VUR disappeared (83% total correction). Recurrence was observed in 4 patients, at 3 months, one year and two years (2 cases). 3 patients had reinjection (2 success, 1 failure). Through long term results are still to be evaluated. The results at one and two years seems to confirm the inoucuity and the effectiveness of endoscopic procedure for treatment of congenital VUR. PMID- 2264489 TI - [Endoscopic treatment of ureteral lithiasis. Results of our second series of 100 cases]. AB - The combined utilization of transurethral ureterorenoscopy (TUR) and extracorporeal shock wave lithotripsy (ESWL) have caused a revolution in the treatment of ureteral lithiasis. We present a total 113 TUR due to ureteral lithiasis performed in period of 20 months, from March 1988 to November 1989. In the last ten months of the study we used TUR an ESWL for the treatment of ureteral lithiasis. Results show success in 92.93% of the treatments; 8 cases of open surgery (7.07%), five of these were performed during the first 10 months of the study, when ESWL was not available, with only 2 serious complications (1.75%) and one death due to massive pulmonary embolism. TUR is an unsubstitutable technique for the treatment of ureteral lithiasis and when combined with ESWL obtains optimum results. It is our technique of choice in all cases non susceptible to treatment with in situ ESWL due to the impossibility of locating the lithiasis without auxiliary endourological manoeuvres. PMID- 2264490 TI - [Surgical treatment of urinary stress incontinence in women]. AB - Long-term results obtained in 54 surgical procedures to correct effort urinary incontinence performed in 49 patients with this pathology are reviewed. One group was treated with suprapubic urethrovesical suspension with the Marshall-Marchetti Krantz technique; the other group with endoscopic suspension of the neck of the bladder, with the Stamey technique and the third group with sling techniques. The authors conclude that any of the surgical techniques achieving a correct reposition of urethrovesical anatomy, rising the posterior urethra to its primitive anatomical bed, obtain a similar success rate. PMID- 2264491 TI - [Hematocele of the tunica vaginalis]. AB - Hematocele in the tunica vaginalis, specially non-traumatic or in previously coagulated cases, is an issue almost ignored by the present urological literature. We have reviewed hematoceles due to the finding of four non-traumatic hematoceles, highlighting the difficulties of a preoperative diagnosis. PMID- 2264493 TI - [Carcinosarcoma and papillary transitional cell carcinoma coexisting in the same bladder]. AB - A case of synchronically coexistent carcinosarcoma and transitional cell carcinoma, with separate neoplastic processes in the same urinary bladder is presented. This tumour association is as far as we know, the second case reported in the literature. Carcinosarcoma was formed by an epithelial component represented by a high level transitional cell carcinoma and a mesenchymal component characterized by an unspecific fusocellular sarcoma with chondrosarcomatous differentiation. An immunohistochemical analysis was performed, confirming the dual nature of the carcinosarcoma. PMID- 2264492 TI - [Enterovesical fistula caused by a prosthesis made of synthetic material]. AB - Enterovesical fistulas affect mainly male patients, due to the interposition of the uterus in women. They can be caused by neoplastic, inflammatory or traumatic processes. A case of ilovesical fistula due to migration of a silastic plate used to repair an epigastric infissional hernia is presented. This case has two distinctive features: first, the cause is extraurological, causing a fistula between both systems due to an inflammatory process. Secondly, we report the long distance travelled by the synthetic mesh, causing a peculiar clinical picture five years after its implantation. PMID- 2264494 TI - [Renal oncocytoma. Presentation of a case]. AB - One case of renal oncocytoma whose diagnosis was established after radical nephrectomy is presented here. The histological heterogeneity of this tumour indicates that the safest treatment is still the radical nephrectomy, at which time diagnosis is most often established. Our case has a special interest as it presented two hepatic lesions suggestive of metastasis. PMID- 2264495 TI - [Bilateral renal adenocarcinoma: relationship with phakomatosis]. AB - Von Hippel-Lindau disease is a very uncommon finding in our environment. A case of an incidental finding of that entity expressed through retinal angioma, bilateral renal cysts and bilateral renal carcinoma is described. A surgical course was followed performing a radical left nephrectomy, given the large size of the tumour, and right lower partial nephrectomy, as well as a review of the renal cysts considering the big tendency they have to degenerate in the disease. PMID- 2264497 TI - [Ectopic gas as a complication of surgical kidney biopsy]. AB - Since the complications herewith presented as a consequence of surgical renal biopsy are really exceptional and references found in the existing literature rare, we have considered that the contribution of these two cases which developed a pneumomediastinum-pneumoperitoneum and pneumocele prespectively during the immediate post-surgical period would be of interest. Evolution was favourable in both cases, with spontaneous resolution of the process. PMID- 2264496 TI - [Leiomyoma of the bladder as a cause of unilateral ureteral obstruction associated with uterine leiomyoma and polycystic ovary]. AB - A case of a female patient with bladder leiomyoma associated to uterus containing several leiomyomatous nodules and polycystic ovaries is presented. The diagnostic convenience that ecography can provide, showing neoformations and their definition with regard to neighbouring organic structures, is highlighted. The existing relationship between uterine leiomyomas and estrogens is outlined, as well as the action of GnRH agonists on such leiomyomas after long-term therapy. PMID- 2264498 TI - [Tuberous sclerosis. Multiple kidney pathology. Presentation of a case]. AB - A clinical case of a 50 year old male, diagnosed in 1984 as having renal polycystosis is presented; four years later, due to the availability of complementary exploratory methods with better resolution and a detailed examination of the patient, the presence of tuberous sclerosis with multiple organ involvement was confirmed. It is noteworthy his florid renal pathology with multiple angiomyolipomes and cysts associated to lithiasis, on a horseshoe kidney. It was this fact that encouraged us to publish the case due to its originality. PMID- 2264499 TI - [Systemic candidiasis and ureteral fungus ball. Ketoconazole and irrigating solutions in the management of urinary candidiasis]. AB - A case of systemic candidiasis is presented in a patient with one kidney in the post-operative period from a cysto-prostatouretrectomy with Bricker ureteroileal derivation, performed due to multifocal superficial vesical tumour non controllable by endoscopy. The clinical picture developed with anuria and temporary diuresis periods associated to a severe septic picture; a deep Candida albicans infection was demonstrated by laboratory tests and a fungus ball ureteral obstruction was demonstrated by radiology. Urinary derivation by means of percutaneous nephrostomy, associated with oral treatment with ketoconazole and local treatment with amphotericin B solution intermittently irrigated through the nephrostomy allowed the patient's resuperation and the fungus ball was spontaneously ejected after 30 days of treatment. The different forms of presentation of urinary candidiasis are discussed together with the diagnostic methods and present therapeutical options, with special reference to the imidazole derivative ketoconazole and irrigation solutions. PMID- 2264500 TI - Histophysiology of the circulating platelet. AB - The role of platelets in hemostasis and thrombosis has been well established since Eberth's and Schimmelbusch's pioneering intravital microscopic experiments. A century ago the distinct features of the circulating "smooth disc" and the activated "spiny sphere" were described. Since then the underlying cell biological processes transforming a harmless floating platelet into a sticky corpuscle, ready to release its stores of thrombogenic and atherogenic substances have been unveiled. However, its life-threatening capabilities have evolved from the necessity of preventing equally dangerous blood losses from a pressurized circulation system. As circulation depends on the liquid state of blood, the platelets and the molecules of the plasmatic coagulation system must circulate in an inactive state, to become activated at the site of "demand" to transform the liquid into a solid hemostatic plug. As in nucleated cells the plasma membrane, made up of a phospholipid bilayer with integrated glycoproteins, is the structure signalling environmental information to the platelet interior. Many of the receptors for stimulatory or inhibitory mediators elicit a cell-biological response via G-proteins and subsequent Ca2+ mobilization by IP3, or stimulation/inhibition of adenylate cyclase followed by changes in cytoplasmic levels of cyclic AMP. The supposed intracellular Ca2+ store of the platelets, the dense tubular system, also appears as the site of Ca2(+)-activated prostaglandin synthesis. Raised cytoplasmic Ca2+ levels promote the polymerization of G-actin to F-actin involved in the extension of pseudopodia in the course of "external shape change." Ca2(+)-activated myosin light-chain kinase phosphorylates myosin which becomes associated with F-actin, with the resulting acto-myosin complex providing the contractile force for "internal shape change," i.e., the centralization of organelles and for clot retraction later in hemostasis. More than by the three-dimensional actin cytoskeleton proper, the discoid shape typical of the nonstimulated platelet appears to be secured by a two-dimensional membrane skeleton of actin filaments anchored to membrane glycoproteins via actin binding protein or spectrin and ankyrin. Although the microtubule coil has been confirmed as the main determinant of the mechanical stiffness of the platelet with biophysical techniques, its hitherto assumed role for the maintenance of the disc shape no longer appears tenable. The morphological phenomenon of the shape change comprises an alteration of membrane glycoproteins resulting in binding of "adhesive" molecules like fibrinogen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2264502 TI - Defining child maltreatment: ratings of parental behaviors. AB - This study investigated adolescents' assessment of various forms of child abuse and neglect. Participants (N = 204) rated the seriousness of vignettes describing a variety of parental actions relative to the degree of harm each was perceived to have on a child's welfare. Adolescents' responses were compared to those of community members and professionals as reported by Giovannoni and Becerra (1979). Results indicated that adolescents were somewhat similar to community members in their ratings; however, they were more severe in their judgments of parenting behaviors on 52 of the 65 items. As a group, adolescents were very critical of the parents' actions, suggesting that they are highly idealistic regarding parental treatment of children and may maintain inappropriate expectations for those responsible for raising children. PMID- 2264501 TI - Change in adolescent boys at teen ranch: a five-year study. AB - A five-year study was undertaken to assess the effectiveness of the Teen Ranch 70 bed residential treatment program for adolescent boys. To date, no long-term study of treatment effectiveness has been conducted; research has concentrated on recidivism, and while this provides some meaningful information, it provides little or no data to treatment directors, therapists, and administrators concerning in-process therapy or client change issues. The present study compared 120 full psychological test and retest batteries of boys who were in the program for at least one year. Through test-retest analysis, 27 intellectual and personality variables were compared to describe changes that took place. Nine intellectual and academic change variables and nine personality change variables were found to be significant. These changes were utilized to examine the overall effectiveness of the Teen Ranch residential treatment program and the possibility of integrating evaluation and treatment processes. PMID- 2264503 TI - Relations between early childhood care arrangements and college students' psychosocial development and academic performance. AB - Associations were explored between early substitute care and white middle-class college students' psychosocial development and academic performance. One set of analyses explored associations with the amount of substitute care experienced throughout early childhood (infancy and at ages 2 and 4) and college students' development; another set explored associations between amount of substitute care during infancy (none, part-time, or full-time). Substitute care experience during infancy alone did not differentiate students on the Erikson Psychosocial Inventory Scale (EPSI). There were some near-significant differences on the EPSI among students in different child care arrangements throughout early childhood, but these did not present a consistent pattern. Students' care experience also did not predict the number of extra-curricular activities in which they were presently involved or whether they chose people- or thing-oriented academic majors. However, no day care in infancy followed by full-time day care at ages 2 and 4 was the best predictor of above-average high school academic achievement, and part-time care throughout infancy and early childhood was the best predictor of average high school academic achievement. PMID- 2264504 TI - Social skills and depression in adolescent suicide attempters. AB - The relationship among depression, social skills, and suicidal behavior was examined in a sample of 41 adolescents hospitalized in a general medical setting following a suicide attempt. These subjects were compared to 40 nonsuicidal psychiatrically hospitalized adolescents. Level of depression, assessed using the Children's Depression Inventory (CDI), and social skills, assessed via the Matson Evaluation of Social Skills with Youngsters (MESSY), were evaluated for all subjects. The suicide attempters and psychiatrically hospitalized patients were not found to differ on either the CDI or MESSY. However, multiple regression analyses revealed the factor scores of the MESSY to be related to depression in both patient groups. The data provide support for the relationship between social skills and depression. Results are also discussed in terms of the similarities between adolescent suicide attempters and nonsuicidal psychiatrically disturbed adolescents. PMID- 2264505 TI - Community service among college and university students: individual and institutional relationships. AB - Increased interest in moral education and prosocial learning behavior has focused attention on the performance of community service by college students. Drawing from the literature on voluntary action and related fields, this study surveyed 1,960 students in eleven institutions of higher education in a southeastern state. Results revealed connections between frequency of community service and both individual and institutional characteristics. However, only two personal variables showed significant relationships to community service in each of the institutional categories: Spiritual/religious values were positively associated with service, while an emphasis on professional success was found to have a negative relationship. These findings offer fresh evidence of the importance of human values in the development of prosocial behavior. PMID- 2264506 TI - MMPI profiles of adolescent substance abusers in treatment. AB - The non-K-corrected MMPI profiles of 243 adolescents presenting themselves for chemical dependency treatment in a residential setting were examined. Results suggested a general lack of psychopathology in this population, although a significant elevation on the Pd scale did emerge. These data are compared to the findings of previous studies with both adolescent and adult populations. PMID- 2264508 TI - Decision-making processes of youth. AB - Research supports the theory that after administrators make a decision, feedback, both positive and negative, and also the administrators' perceived security vis-a vis their position affect their level of commitment to a course of action. However, this research fails to recognize that subjects of college age playing administrators in the simulated, experimental treatments which have been presented in the research had nothing personally to lose if they made a bad decision--an orientation contradictory to the reality of most actual administrative positions. Additionally, the research ignores the interactional effects of the personality of decision makers in terms of their anxiety levels and the judgments they make. This study took both of these considerations into account by creating a decision-making situation within which prospective administrators made monetary commitments to long-term goals while their anxiety level, both as a basic personality attribute and an index of the reality of the decision-making process, was monitored under conditions of varying levels of job insecurity and resistance to their policies in relation to their decisions. Analyses revealed that contrary to the results of past research which used college students as subjects: (1) there is a significant negative correlation between levels of anxiety and commitments to previously chosen courses of action; (2) there are no significant effects of job security on commitment; and, most importantly, (3) high resistance to a policy decision leads to significantly less monetary commitments to long-term goals. The findings suggest that the basis for the contradictory results lies with the anxiety level of decision makers and the realism of experiencing a loss by making poor decisions. PMID- 2264507 TI - Family interactions and sex education in the home. AB - Despite the tremendous growth of family systems theory in recent years, sex education within a family systems context has received little attention. This study examined patterns of interaction within the family and the possible relationship of these patterns to the amount of sex education occurring in the home. Ninety-six adolescents (ages 13-14, 43% male, 90% Caucasian) and the parents of 63 of them (61 mothers and 45 fathers) completed three questionnaires: (1) FACES-II, a measure which categorizes family interactions as Balanced, Midrange or Extreme based on the two dimensions of cohesiveness and adaptability; (2) the Parent-Adolescent Communication Scale; and (3) the Home Discussion Questionnaire, a measure of the amount of discussion about 17 sex education topics. Adolescents who reported open communication and satisfaction with family interactions reported significantly more sex education in the home. Although mothers' reports of sex education were not related to their perceptions of family communication or interactions, fathers who reported the healthiest family interactions also reported the most involvement in the sex education of their adolescent. PMID- 2264509 TI - The relationship of career goal and self-esteem among adolescents. AB - The purpose of this study was to investigate the relationship of career goal and self-esteem among adolescents. A sample of 221 high school sophomores and juniors was administered the Rosenberg Self-Esteem Scale (RSE). Their teachers also were asked to rate the students' self-esteem using the Self-Esteem Rating Scale for Children (SERSC). It was found that, on both the RSE and SERSC, adolescents with some career goals had significantly higher self-esteem than did those without any career goal. PMID- 2264510 TI - Sexual confusion among certain college males. AB - In dealing with college age (18-22) males, clinical observations have shown a fairly common inability to successfully form intimate relationships with same-age females. This problem often appears to be due to an inability to bond and trust that is rooted in the formative years in the nuclear home. When this happens, the young male frequently develops a fear of being sexually abnormal, perhaps even homosexual. This manifests itself in shame, anxiety, depression, denial, reaction formation, performance anxiety, concern about being found out, isolation, substance abuse and, occasionally, acting out. Getting such persons to admit these fears is generally extremely difficult, requiring gentle and empathetic, but persistent, probing on the part of the therapist. Therapy consists of understanding and acceptance by the client that these fears are most often reactive, that they are commonly held, and that when they are seen in proper perspective, they often diminish. The present paper reviews some of the literature on sexual developmental issues of the adolescent male as a backdrop for this problem. The specific difficulties related to reactive homophobia are explored, and some therapeutic approaches suggested. PMID- 2264511 TI - Gender comparisons of college students' attitudes toward sexual behavior. AB - Questionnaires were distributed to 641 undergraduates at a large southeastern university to elicit opinions concerning various forms of premarital sexual behavior. Hypotheses were developed to determine whether there were differences between the attitudes of males and females. Significant differences were found between males' and females' attitudes toward premarital sex when the couple is casually acquainted, and attitudes toward extramarital sex, oral-genital sex, and anal sex. However, significant differences were not found between males' and females' attitudes toward premarital sex when the couple is in love, attitudes toward premarital sex when the couple is engaged, and attitudes toward masturbation, homosexuality, and sexual fantasizing. Males' attitudes toward various forms of sexual behavior were more liberal than those of females. PMID- 2264513 TI - Parental responsibility of African-American unwed adolescent fathers. AB - This study investigated factors related to adolescent fathers' willingness to take parental responsibility for their children. Data were collected on a convenience sample of 43 African-American unwed adolescent fathers. Demographic information was gathered, and self-image was measured using the Offer Self-Image Questionnaire. An author-developed questionnaire measured father's parental responsibility, his own role expectations, and the perceived role expectations of his partner and parents. The findings indicated that father's parental responsibility was influenced by his own role expectations and self-image. The perceived role expectations of his partner and parents were not related to his willingness to take parental responsibility. This study helps adolescent care providers in various settings to become familiar with some of the issues related to teenage fathers, and assists them in determining appropriate interventions. PMID- 2264514 TI - Development of a tool to assess suicide risk factors in urban adolescents. AB - Dramatic increases in the adolescent suicide rate over the past three decades have underscored the need for risk-assessment tools. The tools that do exist are oriented to older populations and their application to adolescents is questionable. A project was initiated at the University of Utah's Health Education Department to develop a pilot instrument to examine the differences between adolescents who have attempted suicide and other teenagers. Eighty-two subjects between the ages of 14 and 19 participated in the test of this instrument. Twenty-five subjects were identified by a physician or psychologist as having failed in a sincere suicide attempt within the previous 18 months. Fifty-seven nonsuicide attempters with similar demographic profiles served as a comparison group. An 86-item questionnaire was administered to both groups. Questions were generated from a review of the literature of the past three decades for problems associated with suicide in this population. Questions were sorted into three domains (family environment, social environment, and self perceptions), with each domain having several subdomains. Statistical analysis revealed significant differences for each of the three domains and on 55 of 86 questions. The results were used to create a streamlined instrument for assessing suicide risk that can be administered in 20 minutes. PMID- 2264515 TI - Adolescent substance abuse: practice implications. AB - The incidence of substance abuse and implications for practice are reviewed. Variables that might be altered to prevent abuse among clients are discussed. Substance abuse theory, school and peer environment, family, the media, community movements, and business and industry are explored in regard to prevention and treatment. PMID- 2264512 TI - Initial parenting attitudes of pregnant adolescents and a comparison with the decision about adoption. AB - The Adult-Adolescent Parenting Inventory was used to examine the initial parenting attitudes of a sample of pregnant adolescents. In addition, the attitudes about parenting were correlated with the decision of the adolescent to either keep or place the baby for adoption. Pregnant adolescents scored significantly lower on the "expectations for children" construct than all groups of controls. They scored significantly higher than adolescent controls on the "empathy" construct but lower than the adult controls. On the "corporal punishment" construct, they scored significantly lower than nonabused adolescent controls but were similar to abused adolescent controls. On the "role-reversal" construct, they scored significantly higher than abused adolescent controls, lower than adult controls, and about the same as nonabused adolescent controls. Adolescents who placed their babies had significantly lower scores on the role reversal measure, but the differences between keepers and placers on the expectations, empathy, and corporal punishment dimensions were not significant. The results are discussed in terms of (1) the areas where attitudes about parenting are below appropriate levels, (2) the possibility of competent teenage mothers, and (3) the groundwork necessary for preparing adolescents for parenthood should they elect to keep their babies. PMID- 2264516 TI - The impact of parental loss on adolescents' psychosocial characteristics. AB - This study examined ten measures of personality, self-image, and emotional and family problems in a sample of 2,158 Australian adolescents, some of whom had suffered parental loss. The data reveal a pattern of poorer adjustment in adolescents who have lost a parent, but clearly demonstrate that type of loss and family reconstitution have no differential effects on psychosocial development. Implications for future research are discussed. PMID- 2264517 TI - Daydreaming and curiosity: stability and change in gifted children and adolescents. AB - Developmental differences in daydreaming and curiosity based on cross-sectional data have been reported, but longitudinal data are lacking. Patterns of longitudinal stability and change in two intellectual styles, daydreaming and curiosity, in gifted children and adolescents are described in this paper. Seventy-four intellectually gifted children attended a special program during two consecutive summers. Self-reports of their frequency of and attitudes toward daydreaming and two measures of their curiosity were obtained each year. The findings suggest a pattern of both change and stability in intellectual styles over time. Measures which tap the content of daydreams changed over time, but measures of process or ways of relating to the environment, such as curiosity and frequency of daydreaming, were fairly stable. PMID- 2264518 TI - Social support and gender role attitude among teenage mothers. AB - This study identifies some of the factors that account for a relatively flexible gender role orientation among adolescent mothers. Education and support from family, peers, and the father of the child(ren) were predictive of a positive attitude toward combining career and child-care roles and competing in the labor market on an equal basis with males. The implications are relevant for school based and social programs designed to enhance competent attitudes and performance among young mothers who are preparing for careers. PMID- 2264519 TI - Potential nutrition messages in magazines read by college students. AB - Advertisements in magazines read by 12% or more of college students enrolled in an introductory nutrition class were surveyed for hidden food and nutrition messages. Meanings were identified by categories of activities, products, and people. Less than 10% of the ads featuring people fell into food categories. Of these, more were for alcohol and supplements; fewer were for basic or extra calorie foods. Hidden messages for females could imply beauty through fashion products, beauty aids, and supplements but with a nutrition slimming plan. Males may be receiving a subtle message that food choices do not matter, and that alcohol and supplements are desirable in everyday life. PMID- 2264520 TI - Parent-adolescent communication, family functioning, and school performance. AB - This paper presents the results of a test of theoretical postulates proposed by Olson, Russell, and Sprenkle (1983) using a matched set of adolescents and their parents. One set of families (n = 40) consisted of adolescents who had been unsuccessful in public school and were attending alternative schools, while the other (n = 52) was a matched group of public school adolescents and their families. Results showed predicted differences in the direction of greater balanced functioning (i.e., optimal cohesion and adaptability) and more positive communication in the public school families. Public school families also perceived greater congruence between perceived and ideal family functioning. Congruence and differences between adolescent and parent perceptions, the importance of positive communication for optimal functioning, and implications for family treatment are discussed. PMID- 2264521 TI - Analysis of a double-layered support system. AB - This analysis focuses on the support functions of a social network consisting of the families, educational staff, and peers of 33 adolescent females. These women were lower-class school dropouts who joined the Israeli Army and--toward the end of their service--participated in a six-month intensive program of educational upgrading. The program was administered by the Israeli Army and operated by female soldiers close in age, but not in social background and education, to the program's participants. Data were collected by a semi-structured interview and analyzed in terms of the emotional, cognitive, and behavioral support functions of the social network. Analysis shows that (1) whereas the educational staff and the peers provide the young women with all three types of support, their parents' is limited to some aspects of emotional support, and is conditional (to success); (2) the educational staff also induced the peers to act as supporters; and (3) as a result, the participants had access to a "double layer" of emotional, cognitive, and behavioral support, and benefited from being both recipients and providers of support, in the coping-enhancing conditions of sociocultural and situational similarity. PMID- 2264522 TI - The TOL plasmids: determinants of the catabolism of toluene and the xylenes. PMID- 2264523 TI - Microbial stress proteins. AB - There is general agreement that a function, perhaps the major function, of stress proteins under normal physiological conditions is to help assembly and disassembly of protein complexes and to catalyse protein-translocation processes. It remains unclear, however, as to what role these processes play in stressed cells. It could be that cells under stress produce abnormal, misfolded or otherwise damaged proteins and that increased synthesis of stress proteins is required to counter protein modifications. A role for stress proteins in recovery of cells from stress, as opposed to a role in helping cells to withstand a lethal stress, is thus suggested. The intracellular location of stress proteins, in the unstressed and stressed cell, is worthy of further studies. Members of the hsp70 family are associated with the cytosol, mitochondria and endoplasmic reticulum. There is evidence, particularly from studies on mammalian cells (Tanguay, 1985; Welch and Mizzen, 1988; Arrigo et al., 1988), that following stress hsps migrate to various cellular compartments and subsequently delocalize after stress. However, there is little comparable data from microbial systems for this phenomenon (e.g. Rossi and Lindquist, 1989). The question as to the role of stress proteins in the transient acquisition of thermotolerance remains to be answered. It is insufficient to equate the kinetics of stress-protein synthesis with acquisition of thermotolerance. Quantitative data on the amount of stress protein present at various times, including the recovery period, is required. The demonstration that microbial stress proteins are important antigenic determinants of micro-organisms causing major debilitating diseases in the world is an exciting observation. Studies on the interplay of pathogen and host, both carrying similar antigenic hsp determinants, will be a challenging area for future research. It is likely that E. coli and Sacch. cerevisiae, with their well established biochemical and genetic properties, will continue to be the experimental systems of choice for studies on stress proteins. On the other hand, it is encouraging that studies on other micro-organisms have expanded in the past few years and have made substantial contributions towards our understanding of the stress response. The ubiquitous nature of the stress response and the remarkable evolutionary conservation of the stress proteins continue to be attractive areas for research. PMID- 2264524 TI - Microbial anaerobic respiration. PMID- 2264525 TI - Recent research into the physiology of Mycobacterium leprae. PMID- 2264526 TI - Human immunodeficiency virus type 1 infections in children. PMID- 2264527 TI - Anabolic steroid abuse. AB - Anabolic steroids are capable of increasing strength and muscle bulk in certain individuals when combined with a proper diet and an intense training program. Any steroid that is anabolic is also androgenic. Anabolic steroids are fraught with numerous side effects, a few of which are potentially life threatening, and some of which are permanent. Most of the side effects are mild and reversible. Use of anabolic steroids in sports is as much a moral issue as a medical one. Drug testing has not been a very successful means to eradicate abuse in the sporting arena. Education alone is probably not the answer to stopping anabolic steroid abuse but is an essential first step in combating this problem. Use of anabolic steroids in athletes is a form of cheating, and use will likely continue, especially if the rewards for success in sports remain so high. Physicians should avoid condemning individuals who choose to use anabolic steroids and encourage discussion of use with their health providers. PMID- 2264528 TI - The kidney in systemic diseases: Part I--Infectious, hematologic, and malignant liver and metabolic diseases. PMID- 2264529 TI - Perinatal grief and mourning. AB - The grief and mourning that parents experience following a perinatal loss is as devastating as the loss of an older loved one. The pattern of mourning can be anticipated and interventions can be implemented. With proper help, the parents can pass through this catastrophic time in their lives with a minimum of scars. If the physician stops, reaches out, listens, and supports the parents, he or she can have a dramatic effect on the lives of these parents. In the same manner in which we started this paper, we close with a quotation from another parent who suffered a loss: Daughters may die, But why? For even daughters can't live with half a heart. Three days isn't much a life. But long enough to remember thin blue lips, uneven gasps in incubators, Racking breaths that cause a pain to those who watched. Long enough to remember I never held her Or felt her softness Or counted her toes. I didn't even know the color of her eyes. Dead paled hands not quite covered by the gown she Was to go home in. Moist earth smell. One small casket. And the tears. You see, I hold in my hand but souvenirs of an occasion. A sheet of paper filled with statistics, A certificate with smudged footprints, A tiny bracelet engraved "Girl, Smith." You say that you are sorry That you know how I feel. But you can't know because I don't feel. Not yet. PMID- 2264531 TI - Pathology of transplant rejection and immunosuppressive therapy: Part I--Graft vs.-host disease and organ rejection. PMID- 2264530 TI - Transplantation immunity: basic principles and future projections. PMID- 2264532 TI - Pathology of transplant rejection and immunosuppressive therapy: Part II- Pathologic effects of immunosuppressive therapy. PMID- 2264533 TI - Advances in pediatric liver transplantation. PMID- 2264534 TI - Pancreas and islet cell transplantation for type I diabetes mellitus: does it have a role for children? PMID- 2264535 TI - Pediatric heart transplantation. AB - Heart transplantation has been performed successfully in the pediatric age group for just over 10 years, yet early results are encouraging, and this procedure has moved from the realm of experimental therapy to that of accepted medical practice for certain specific conditions. In infants and children with cardiomyopathies or with congenital heart disease for which no reasonable standard surgical alternative exists, heart transplantation offers the best hope for long-term survival. Most important, in those patients surviving heart transplantation, rehabilitation has been almost universally complete. Although the long-term prospects for pediatric heart transplant patients are still unknown, we have now accumulated sufficient experience in adults suggesting the potential for decades long survival. Future improvements in diagnosis and treatment of rejection and prevention of the complications of immunosuppressive therapy will continue to improve the prospects for lifelong survival in these patients. PMID- 2264536 TI - Recurrent childhood myoglobinuria. AB - Recurrent heritable childhood myoglobinuria is a potentially fatal entity (mortality up to 35%) in which prompt diagnosis and treatment are critical. Sixty childhood cases have been reported between 1910 to 1988, most with undiagnosed etiologies. We have studied an additional 40 cases referred to CPMC (1980-1988), suggesting that this condition is largely underdiagnosed or unreported. We have found important differences between the childhood and adult-onset cases. Of 77 cases of adult-onset recurrent myoglobinuria, 45% have been diagnosed biochemically. In contrast, only 30% of the 60 childhood cases from the literature have been diagnosed; 11 with CPT deficiency and 7 with various glycolytic defects, and only 5 of our 40 childhood cases have been diagnosed, all with CPT deficiency. The 100 combined childhood cases can be divided into an exertional group (type I) with exertion as the leading precipitating factor (46 literature and 10 CPMC cases), a toxic group (type II) with infection and/or fever as the primary precipitant (14 literature and 23 CPMC cases), and 7 undefined cases. The type I group resembles the adult-onset group in which exercise is also the leading precipitating factor. There is a slight female predominance (male/female = 1:1.3) in the toxic group vs. a marked male predominance in the exertional and adult groups (4:1). Only 4 of 37 cases (11%) of the toxic group are diagnosed (all with CPT deficiency) vs. 19 of 56 cases (34%) of the exertional group (12 CPT, 7 glycolytic) and 45% of the adult group. The toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features, including ictal bulbar signs (8 of 18), encephalopathy (4 of 19), and seizures (2 of 7), as well as persistent cardiac abnormalities, developmental delay (4 of 17), and dysmorphic features (2 of 9). These clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies. A study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block. PMID- 2264537 TI - [Detection of polyamines by a new enzymatic differential assay. (7) Fundamental study on a new enzymatic differential assay of tissue polyamines]. AB - The enzymatic method for isolation and determination of urinary polyamines was modified to measure the polyamines in tissue. High recovery rates of polyamines in tissue by the enzymatic method were obtained, namely, 104.5 +/- 7.4% for diamine, 104.7 +/- 23.3% for spermidine and 104.8 +/- 7.5% for spermine. The results obtained by this method correlated well with those obtained by high performance liquid chromatography, and a close correlation was demonstrated for all fractions: diamine r = 0.8991, y = 0.9916x + 0.0499; spermidine r = 0.8936, y = 1.2073x + 0.1005; spermine r = 0.8921, y = 1.2200x-0.2194, (n = 13). PMID- 2264538 TI - [Detection of polyamines by a new enzymatic differential assay. (8) Studies on tissue polyamine concentrations in patients with genitourinary malignant diseases]. AB - Polyamine concentrations of human cancerous and non-cancerous tissues from the kidney, ureter, bladder were measured by a new enzymatic method for isolation and determination of polyamines. In cancerous and non-cancerous tissue of the organs studied, the spermine level was highest followed by the spermidine and diamine levels. The concentrations of diamine, spermidine and spermine in cancerous tissues were significantly higher than those in non-cancerous tissues, but there was no significant difference in the spermidine/spermine ratio between the cancerous and non-cancerous tissues. These data suggest that polyamines are produced above the normal levels in pathological conditions such as renal cell carcinoma, ureteral cancer and bladder cancer. PMID- 2264539 TI - [Clinical evaluation of serum S100ao protein in patients with urogenital diseases and healthy volunteers]. AB - We investigated the clinical significance of the serum S100ao protein in patients with urogenital diseases. The serum levels of S100ao protein were measured in 179 patients with urogenital diseases and 180 healthy volunteers. The mean value of S100ao protein in serum from healthy volunteers was 203 +/- 107 pg/ml (Mean +/- SD). Therefore, the cut-off level was set to 524 pg/ml (Mean +/- 3SD). The levels of S100ao protein in serum were significantly higher in men than in women (P less than 0.05). The levels of S100ao protein in serum were significantly high in the patients in their fifties and sixties compared with the other patients (P less than 0.01). When serum levels exceeding the cut-off level were considered to be positive, the percentages of positivity in each disease were as follows: renal cell carcinoma; 38.7%, bladder tumor; 9.1%, prostatic carcinoma; 12.5%, testicular tumor; 0%, benign prostatic hypertrophy; 7.4%, urolithiasis; 7.1% and chronic renal failure; 100%. The levels of S100ao protein in serum were significantly correlated with those of BUN, serum creatinine and endogenous creatinine clearance, respectively. S100ao protein in serum was increased immediately after operation and returned to the normal range within one to two weeks after operation. As described above, the level of S100ao protein in serum was affected by renal function, operative procedures and age. However, the positive rate of S100ao protein was so high in patients with renal cell carcinoma that serum S100ao protein might be a valuable tumor marker in those patients. PMID- 2264540 TI - [Surgical treatment of renal cell carcinoma with bone metastasis]. AB - Eighty-six patients with renal cell carcinoma underwent radical nephrectomy in Chiba Cancer Center Hospital. Fifteen of the 86 patients developed bone metastases. Seven of the 15 patients with bone metastases had received chemotherapy and radiotherapy. Six of the 15 patients underwent surgical treatment and two received radiotherapy alone. Of the six patients treated surgically for bone metastases, two patients were treated with wide resection and the remaining four patients underwent excision of the metastatic lesions in combination with radiotherapy, chemotherapy or immunotherapy. One of the two patients who underwent wide resection of a pelvic bone lesion is alive without evidence of disease for 6 years and 4 months. Another patient who underwent wide resection of femoral bone lesion survived for 14 years and 2 months but died of recurrent cancer. Pathologic findings of renal cell carcinoma in the long-time survivors showed adenocarcinoma of alveolar type of clear cell subtype and in grade 1. Wide resection of bone metastases of renal cell carcinoma can significantly prolong the survival time and improve the quality of life of the patients. PMID- 2264541 TI - [Evaluation of the results of extracorporeal shock-wave lithotripsy (ESWL) for solitary upper urinary tract stone]. AB - At Osaka City University Hospital, we performed extracorporeal shock-wave lithotripsy (ESWL) for 1277 patients in a total of 1788 sessions using Dornier kidney lithotripter Model HM III from July, 1985 to the end of December, 1988. Among the patients with a solitary stone, 911 cases were available for the follow up study and we have compared the results among these cases in respect to the stone location and size. The results obtained were as follows: the ratio of kidney stone to ureter stone was found to be 2.2:1 in male, and 3.8:1 in female patients. This indicates that ureter stones are more frequently found in male than in female patients. In addition, we compared the size of kidney stones found in the patients including 415 male and 243 female patients. Stones larger than 20 mm were more frequently found in female than in male patients. Moreover, a stone composition study of these patients showed that the contents of both phosphate calcium and magnesium ammonium phosphate were higher in female than in male patients. ESWL performed against stones at pelvis and calyces exhibited the best results. The results obtained with the stones less than 20 mm in diameter were especially favorable with a success rate of 100% for the stones less than 10 mm and 83% for the stones 10-20 mm, in diameter, while the results with the stones larger than 20 mm in diameter were rather poor with a success rate of 31%. ESWL performed against ureter stones showed poor results with a success rate of 63% for the stones smaller than 20 mm in diameter. PMID- 2264542 TI - [A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer]. AB - We reviewed 76 cases of renal pelvic and ureteral cancer, admitted to our hospital between January, 1975 and December, 1988, with special reference to the occurrence of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 35 of the 76 cases (46.1%), 7 with a preceding bladder cancer, 17 with a coexistent one and 11 with a subsequent one. In case of renal pelvic and upper ureteral cancer the incidence of coexistent or subsequent tumors of the bladder was 28.7% (16 of 56 patients). However, in the cases of lower ureteral cancer the incidence of these tumors was 82.4% (14 of 17 patients). This incidence was significantly higher than that in renal pelvic and upper ureteral cancer. The subsequent bladder cancer was observed in 19 patients including 8 patients who had a recurrence of the bladder cancer after the treatment for a preceding and coexistent bladder cancer. The cancer in most cases occurred within 2 years after the treatment of the upper urinary tract neoplasm. Of 19 patients who had subsequent bladder cancer 11 had primary sites in the renal pelvis and upper ureter. Another 8 patient had primary sites in the lower ureter. Four of the 8 subsequent bladder cancers in patients with lower ureteral cancer occurred just on and around the affected ureteral orifice. All these 4 tumors were high grade and high stage tumors. On the other hand, another 15 patients developed subsequent bladder cancer in a place other than the affected ureteral orifice. Of these 15 patients, 13 cases showed a low grade and low stage tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264543 TI - [A clinicopathological study on patients with bladder cancer treated with cystectomy]. AB - A clinical and histopathological investigation was made on 170 patients with bladder cancer who underwent total cystectomy at our institutions between 1982 and 1986. The overall 5-year survival rates of patients with pTis + pTa, pT1, pT2, pT3, pT3b and pT4 were 100, 71.8, 60.7, 39.2, 31.4 and 0% respectively, those of patients with G1, G2 and G3 were 100%, 67.6%, 35.7% respectively. As for histopathological growth and spread pattern (INF), intramural lymphatic invasion (ly) and venous invasion (v), INF beta, INF gamma, ly2, v (+) showed the worst prognosis. These histopathological factors were considered to be closely correlated to each other. Studies on these histopathological factors are very important in planning the subsequent therapy. PMID- 2264544 TI - [Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma]. AB - Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided. PMID- 2264545 TI - [A morphological study of the testes in patients with idiopathic male infertility -immunohistochemical analysis of collagens and laminin in human testes]. AB - In the human testis, the distribution of extracellular components, such as types I, III, IV and V collagens and laminin, was investigated immunohistochemically by light microscopy. Specimens were obtained by testicular biopsy from 40 patients with idiopathic male infertility and 14 normal adult males. In the normal testes, the basement membrane was positive for types I, III, IV and V collagens and laminin. However, the distribution patterns of these components were different. Furthermore, a reactivity for types I and III collagens was found in the interstitial connective tissue matrix. Immunoreactivity for types I and III collagens was markedly positive in the limiting membranes around the Leydig cells. In the pathological testes, all the layers of the basement membrane of both thickened and obstructed tubules were positive for types I and III collagens. On the other hand, reaction products of type IV collagen were localized in the inner layer of the basement membrane and the peritubular cell (myoid cell) layer, and those of laminin were only found in the inner layer. Type V collagen-reactivity was observed in the basement membrane of thickened tubules. Positive reactions for types IV and V collagens and laminin were seldom recognized in the obstructed tubules. In the interstitial space, the connective tissues were significantly increased as compared with normal testes, which included extracellular components that reacted for types I and III collagens. Histological findings in normal adult testes and pathological testes were compared. Quantitative analysis of mean thickness of the basement membrane (W), mean seminiferous tubular diameter (T), T/W ratio and Leydig cell index demonstrated significant differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264546 TI - [A case of lung metastases of bladder cancer in which thoracotomy was performed following M-VAC therapy]. AB - A case of lung metastases of bladder cancer in which thoracotomy was performed following M-VAC is presented. A fifty-nine-year-old man underwent radical cystectomy and ileal conduit diversion for bladder cancer. Pathological diagnosis was TCC greater than AC much greater than SCC. After nine months, he was admitted because of lung metastases. Three courses of M-VAC therapy brought partial remission. A thoracotomy was performed on residual lung metastasis. Pathological diagnosis was AC much greater than TCC greater than SCC. Because M-VAC therapy has limited antitumor activity against mixed histological bladder cancer, we recommend not only M-VAC therapy but also surgical resection for the metastatic tumor the primary site of which has nontransitional components. PMID- 2264547 TI - [Intracavernous indurations after injuries to the external genital parts caused by a motorcycle tank]. AB - We have experienced 2 cases of intracavernous induration after injuries to the external genital parts caused by a motorcycle tank. Case 1. A 28-year-old male was admitted to our department complaining of painless indurations of the penile radix. Cavernosography showed segmental filling defect in left corpus cavernosum. Because erectile disturbance was noted, resection of the induration was carried out. Microscopic section of the excised tissue showed only fibrosis. Case 2. A 20 year-old male visited our clinic with chief complaints of induration of the penile radix and erectile disturbance. Corpus cavernosography demonstrated filling defect in bilateral corpus cavernosum. We recommended the resection of the indurations, but the patient refused. A brief review on etiology and therapy of intracavernous fibrosis was made. PMID- 2264548 TI - [A parathyroid cyst and an adenoma associated with primary hyperparathyroidism: report of a case]. AB - A case of a parathyroid cyst associated with an adenoma in a different gland is reported. A 55-year-old female was explored with preoperative diagnosis of primary hyperparathyroidism after endoscopic removal of a right ureteral stone. The operation revealed a cyst, 20 x 10 mm in size at the left lower gland, and a solid tumor, 32 x 12 x 7 mm in size and 1,300 mg in weight in the left upper gland. Histological examination disclosed a parathyroid cyst and an oxyphilic and chief cell adenoma, respectively. Postoperative course was uneventful including normalized serum Ca level. To our knowledge, 59 cases of parathyroid cysts have been reported in the Japanese literature, of which 31 were in the hyperparathyroid status. The most common causes were cystic degeneration of the adenomas. A parathyroid cyst with a concomitant adenoma in a different gland like our case is very rare. This is the first reported case in Japan and the sixth reported case in the world literature. PMID- 2264550 TI - [The therapeutic effect of norfloxacin on chronic prostatitis]. AB - The clinical efficacy of norfloxacin (NFLX) was evaluated on 40 patients. They had subjective symptoms suggestive of prostate inflammations and more than five white blood cells (WBC)/hpf in their prostatic secretions (EPS) or VB3. Of these, gram negative rods were isolated from the EPS in 3 patients and gram positive cocci were obtained in 26 patients. The overall clinical efficacy was determined at the second week. The effectiveness rate of the subjective symptoms was 82.5%. The effectiveness rate of the WBC in the EPS was 47.4%. The effectiveness rate of the bacteria in the EPS was 64.3%. The overall clinical effectiveness rate was 77.8%. A subjective side effect was observed only in one patient who had skin eruption like urticaria. Mild liver dysfunction of blood chemistry analysis was shown only in two patients but they had had long standing chronic hepatitis. We conclude that NFLX is an effective drug for the patients with chronic prostatitis. PMID- 2264549 TI - [Clinical application of Sonolith 3000 type on extracorporeal shock wave lithotripsy for renal and ureteral stones]. AB - With Sonolith 3000, a new extracorporeal shock wave lithotriptor, we performed extracorporeal shock wave lithotripsy (ESWL) on 34 patients with upper urinary stones, including 5 patients with target stones of this clinical application in both sides. The 39 target stones in the 34 patients were located in the renal calyx (13 cases), renal pelvis (14 cases), renal calyx and pelvis (1 case), renal pelvis and ureter (1 case), and upper ureter (10 cases). The ultrasound-aiming system gave a satisfactory imaging of the target stones in 94.9% of cases (37/39 cases). During the ESWL treatment, 32 patients (94.2%) did not need anesthesia, but 2 patients (5.9%) needed epidural anesthesia because of intolerable pain and/or terror of pain. The average number of treatments per case was 2.08, and the average dose of shock waves per treatment was 3,691.1. The stone-free rate on the 14th, 42nd and 90th days after the last ESWL treatment were 28.2% (11/39), 51.3% (20/39) and 64.1% (25/39), respectively. Out of 39 cases, 31 cases (79.5%) were either stone-free or had only sand-like residual stones on the 90th day. Most cases had minimal side effects, such as transient macroscopic hematuria (100.0%), skin eruption (50.0%) and back pain (41.2%), but one case needed a 1,200 ml transfusion because of perirenal hematoma immediately after 1st session of ESWL treatment with 2,300 shock waves (13 kv). The serum total bilirubin level on 1st day after the last session of ESWL treatment was significantly increased when compared with the preoperative level, but the level was not significantly increased after the 1st session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264552 TI - Urticarial vasculitis. AB - Thirty seven patients with chronic urticaria were prospectively studied from August 1984 to July 1986. These patients were submitted to regular and immunological laboratory tests. Biopsies were taken from recent urticarial lesions for histologic analysis and also to direct immunofluorescence and immunohistochemistry studies. Vasculitis was found in 27% of the patients. Most of them showed only urticarial lesions except two (20%), that presented residual macula; angioedema occurred in 20% of the urticarial vasculitis (UV) patients; most cases had no systemic manifestations. Serum immunoglobulins and circulant immunocomplexes were increased in both groups. Complement reduction was considered an evidence of vascular aggression, being found in 55% of the UV patients. Direct immunofluorescence studies showed only 10% of positive IgM fluorescence in the vessel walls in the UV group. Immunohistochemical evaluation in the same group revealed mainly slight deposition of immunoglobulins IgG, IgM and IgA in the plasma cells of 80% of the samples and in only 10% there was immunoglobulin deposition in the vessel walls. The authors concluded that conventional histopathology is the best diagnosis method for urticarial vasculitis, direct immunofluorescence and immunoperoxidase being ancillary tools. Therefore, a special group of patients was detected, clinically and therapeutically resembling common urticaria patients, but presenting vasculitis in the histologic exam. This fact leads to the hypothesis that there is a range between common urticaria and urticarial vasculitis with systemic involvement. PMID- 2264551 TI - Value of IgG4 antibodies against foods in atopic dermatitis. AB - Various authors have linked IgG4 antibodies to biological activities that are apparently contradictory in different studies. On one hand, it has been confirmed that during immunotherapy with inhalant and Hymenoptera venom antigens, an increase is produced in specific IgG4 levels. On the other hand, it has been suggested that these antibodies can intervene in hypersensitivity reactions, basically when these are directed against food antigens. We studied IgG4 levels against milk and egg fractions in patients with atopic dermatitis (AD) (n = 23), and in healthy individuals (n = 20). Patients with AD had significantly much higher IgG4 levels against egg white (24.16 micrograms/ml), egg yolk (9.96 micrograms/ml) and beta-lactoglobulin (10 micrograms/ml) than those found in healthy individuals (6.75, 3.12, 3.35 micrograms/ml, respectively), with no significant differences for alpha-lactalbumin and casein. Patients with AD without hypersensitivity to egg and milk, at the moment of the study, also had significantly higher levels than those of control individuals, against egg white (27.11 micrograms/ml), egg yolk (12 micrograms/ml) and beta-lactoglobulin (11.72 micrograms/ml). There were no differences in IgG4 levels against alpha lactalbumin, beta-lactoglobulin and casein, when comparing patients with AD and hypersensitivity to milk, and patients with AD without present hypersensitivity to milk. We concluded that patients with AD presented high IgG4 levels against egg and milk fractions, in relation to the healthy population, and that the fraction of milk with the highest antigenic potency was beta-lactoglobulin. PMID- 2264553 TI - Topical nasal immunotherapy. Immunologic response of IgE in nasal secretion after immunotherapy with Dermatophagoides pteronyssinus. AB - We studied 9 children between 9 and 14 years old who had been diagnosed with exclusive allergic rhinitis and were sensitive to acari. Topical nasal immunotherapy for D. pteronyssinus was carried out for 2 years. The total IgE in nasal secretions measured before immunotherapy showed levels of 14.2 to 85.2 IU/ml, and the specific IgE in nasal secretion against D. pteronyssinus and D. farinae ranged from 0.6 to 8.86 PRU (classes II and III). After the immunotherapy the total IgE in nasal secretion fell in 8 of the 9 children (average 24.2 IU/ml. Range 5.6 to 53.3 IU/ml). The specific IgE against D. pteronyssinus rose in 6 children and fell in 3, and all but one of the children remained in class II-III. The tolerance to the immunotherapy was good in all the children. PMID- 2264554 TI - Hyperimmunoglobulinemia E syndrome of neonatal onset. AB - A case of hyperimmunoglobulinemia IgE with recurrent infections of neonatal onset and unfavourable evolution is described. The first clinical finding was the appearance of maculopapular rash in the skin when the child was fifteen days old. From this period onwards, respiratory and cutaneous infections were continuous, leading to a progressive deterioration of the general condition, and malnutrition, which ended fatally at the age of three years. IgE levels were measured on several occasions, this being 17 IU/ml at the onset of the symptoms; afterwards, the mean value was 17.680 IU/ml (Range: 14.9-32.710 IU/ml). PMID- 2264555 TI - Contributions of Seymour Sarason to the field of mental retardation. AB - The contributions of Seymour Sarason to the field of mental retardation are presented against the background of the pivotal changes in society's perception of the retardate that occurred following World War II. Sarason's key contributions to that change in terms of broadening the scientific approach to the issues in the field and advocating reform in the treatment and education of the retarded are briefly sketched. PMID- 2264556 TI - Gender, instrumentality, and expressivity: moderators of the relation between stress and psychological symptoms during adolescence. AB - Examined the roles of gender, instrumentality, and expressivity as moderator of the relations between stressful events and psychological symptoms in samples of junior high (n = 93), senior high (n = 140), and college students (n = 145). Female adolescents in all three samples reported more overall negative events than did males. Females in the junior and senior high samples reported more negative interpersonal stresses than did males. However, there were no indications in any of the samples of a stronger relation between negative events and psychological symptoms for adolescent females than males. Further, there was little evidence that instrumentality or expressivity moderated the relations between negative events and psychological symptoms. In each sample, certain stresses were most strongly related to psychological symptoms: family stresses in the junior high, peer stresses in the senior high, and academic stresses in the college sample. Implications of the findings for developmental changes in stress during adolescence are discussed. PMID- 2264557 TI - Gender differences in emotional support and depressive symptoms among adolescents: a prospective analysis. AB - Investigated components of perceived emotional support, including support from family members, nonfamily adults, and peers, as predictors of depressive symptoms in a sample of 333 high school students (age 14-18) using a prospective design. Analyses of panel questionnaire data at two points in time suggest there are significant gender differences both in the quality of perceived support reported by adolescents and in the importance of support variables as predictors of depressive symptoms. Although there are no gender differences in the magnitude of perceived support from family members, girls report higher emotional support from both nonfamily adults and peers than boys report. Simple correlations between family support and depression are significantly stronger for girls than for boys. Results of hierarchical regression analyses, controlling for initial level of symptoms, reveal that whereas both nonfamily adult and friend components of perceived support are significant predictors of changes in symptoms for girls, none of these variables significantly predicts changes in symptoms for boys in this sample. In addition, initial symptoms predict changes in family support for girls but not for boys. PMID- 2264558 TI - Supportive interactions, negative interactions, and depressed mood. AB - Research on the association between social relationships and emotional functioning has emphasized the health-promoting effects of social support. Yet there is reason to believe that the absence of negative social interactions may be more important for mental health than the presence of supportive interactions. In this investigation we clarify important characteristics concerning the source, the recipient, and the combined influence of support and negativity. Data are presented regarding supportive and negative interactions with spouse, relatives, and friends; regression analyses suggest that negative interactions are more predictive of depressed mood than supportive interactions (specifically with spouse and friends). We also document several specifications suggesting directions for future research on the special importance of interactions in intimate relationships and the synergistic effects of situations in which supportive and negative interactions both occur. PMID- 2264559 TI - Social support and cancer: adult patients' desire for support from family, friends, and health professionals. AB - Examined cancer patients' desire for social support from family, friends, and health professionals upon whom they most depended for support. Before a single interaction with each of these sources, nonhospitalized adult cancer patients (N = 64) completed a questionnaire indicating their desire for support from the source on 11 functional components. Results indicated that emotional and instrumental functions of support were distinct and required separate examination. Distinctiveness of primary sources was manifest by patients' overall preference for tangible aid from family, modeling from friends who had cancer, and open communication and clarification from health professionals. Family and friends were equally preferred sources for dealing with affective reactions to the stressfulness of cancer. All three sources were similarly desired for self esteem enhancement and for relief from decision-making and problem-solving responsibilities. Finally, patients' perceived prognosis but not the objective severity of their illness was associated with a heightened desire for support, especially for instrumental support functions. PMID- 2264560 TI - Ethnicity, culture, and social resources. AB - Assessed social integration (existence or quantity of relationships) and social (specifically, emotional) support in Mexican Americans (MAs) and non-Hispanic whites (NHWs). Ethnic differences were seen as arising from (a) demographic differences between ethnic groups that account for ethnic differences; (b) demographic attributes that have different associations with social resources for each ethnic group; (c) ethnic differences independent of these explanations. Study participants were 538 U.S.-born MA, 706 Mexico-born MA, and 1,149 NHW randomly selected community residents. Immigrants were more often married, and MAs and immigrants reported fewer friends and less emotional support, regardless of demographic attributes. Ethnic differences in demographic attributes accounted for MAs' and immigrants' smaller kin networks. Ethnic differences in demographic correlates of working accounted for MAs' lower employment rates. PMID- 2264561 TI - The adaptation of black graduate students: a social network approach. AB - Despite the importance of increasing the number of graduate degrees awarded to members of minority groups, there has been little research on how minority students adapt to the graduate school environment. The present study examined how social integration and social support were related to academic performance and psychological well-being among 89 black graduate and professional students. Findings indicate that black graduate students were not well integrated into their academic environment. Students in relatively more integrated departments were better adjusted, had higher grades, and perceived themselves to be making good progress in their graduate work. These students were also less likely to have considered dropping out of school. Frequency of out-of-school contact with black faculty and the number of black students in the department were important social integration and social support variables. The implications of these findings for minority student retention are discussed. PMID- 2264562 TI - Asbestos-related lesions of the pleura: parietal plaques compared to diffuse thickening studied with chest roentgenography, computed tomography, lung function, and gas exchange. AB - Lung function tests, tests of working capacity with gas exchange, and computed tomography (CT) with density measurements with the patient supine and prone were performed in 23 males with asbestos-related bilateral pleural lesions. Two had pulmonary asbestosis grade 1/0 or more; all the others had normal lung parenchyma. On x-ray, the pleural lesions were divided into plaques involving only the parietal pleura There was a and diffuse pleural fibrosis of various degrees involving the visceral pleura. There was a good correlation between the findings at plain chest roentgenography and CT, but more lesions were seen on the CT scan. However, a few pleural plaques seen on conventional films were not observed at CT. Individuals with plaques had slightly lowered lung function compared to reference subjects. Bilateral diffuse pleural fibrosis was associated with a marked decrease in pulmonary function. The two patients with radiologically evident pulmonary asbestosis were found in this group. Decreased lung function was also observed in subjects with pleural fibrosis of only grade 1 (involving less than one fourth of the hemithorax) and a normal exercise capacity. The study shows the importance of differentiation between various asbestos-related pleural lesions. PMID- 2264563 TI - Mortality of U.S. embalmers and funeral directors. AB - The causes of mortality of 3,649 white and 397 non-white male U.S. embalmers and funeral directors, who had died between 1975 and 1985, were examined in a proportional mortality study. Non-significant excesses were found for malignancies of the buccal cavity and pharynx (PMR = 120) and for nasopharyngeal cancer (PMR = 216). No sinonasal cancers were observed, while 1.7 were expected. A statistically significant excess of colon cancer (PMR = 127) was found and a non-significant excess of brain and other CNS cancer was noted among whites only (PMR = 123). Statistically significant excesses of malignancies of the lymphatic and hematopoietic systems were found in whites (PMR = 131) and non-whites (PMR = 241). Myeloid leukemia (PMR = 157) and leukemia of other and unspecified cell types (PMR = 228) were in excess, while no excess of lymphatic leukemia was noted. Elevations in risk were also found for non-Hodgkin's lymphoma, polycythemia vera, and myelofibrosis. Non-whites showed a marked excess of multiple myeloma (PMR = 369). Chronic nephritis was in excess among whites (PMR = 215) and non-whites (PMR = 257). No excess of cirrhosis of the liver was found. Excesses of malignancies of the lymphatic and hematopoietic systems could not be directly related to job held in the funeral industry. Further case-control studies are planned to rule out the possibility that the observed associations are artifactual, by assessing the association between specific work practices and disease risk. PMID- 2264564 TI - Cross-sectional study of platinum salts sensitization among precious metals refinery workers. AB - A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems. PMID- 2264565 TI - Mortality and morbidity among Army Chemical Corps Vietnam veterans: a preliminary report. AB - Nearly 1,000 men serving in Army Chemical Corps units in Vietnam between 1965 and 1971 were responsible for the mixing and application of herbicides, riot control substances, and burning agents. Information on Vietnam service was obtained from military records of 94% of this cohort. Follow-up for vital status on December 31, 1987, was conducted using Department of Veterans Affairs (VA), military, National Death Index, U.S. Internal Revenue Service, and Social Security Administration records. Cause-specific observed numbers of deaths among the 894 men included in the study group were compared with the numbers expected based on rates for U.S. men, adjusting for race, age, and calendar period. Fifty-three deaths from all causes were observed during the study period, compared to 48.8 expected (SMR = 1.09). There were statistically significant excesses of digestive disease deaths (SMR = 2.98), primarily due to cirrhosis, and from motor vehicle accidents (SMR = 2.00). Two deaths were observed from leukemia (0.5 expected) and two from brain cancer (0.4 expected). A total of 257 of the study subjects had received VA inpatient care or Agent Orange registry medical examinations during the study period. Two of these subjects had confirmed diagnoses of Hodgkin's disease (expected = 0.7) and one of hairy cell leukemia. Because of the small study group size and the lack of specificity of information regarding their exposures, these results cannot be attributed to any single chemical agent. PMID- 2264566 TI - Use of video display terminals during pregnancy and the risk of spontaneous abortion, low birthweight, or intrauterine growth retardation. AB - Use of video display terminals (VDTs) during pregnancy among working women was examined using data from a large case-control study of spontaneous abortions (SAB) occurring in 1986-1987. The crude odds ratio for SAB and VDT use was 1.2 for use of less than 20 hours per week (95% CI = 0.88, 1.6) as well as for 20 hours or more (CI = 0.87, 1.5), with little change after adjustment for a variety of confounders. The effects of VDT use may vary by the gestational age at SAB, with stronger associations seen in earlier (less than or equal to 12 weeks) compared to later SABs. Use of VDTs within specific occupational categories was examined, yielding adjusted odds ratios varying from 0.5 to 1.7. The risk for low birthweight (LBW) among the control group also was not greatly elevated at either VDT use level, with adjusted ORs of 1.1 (0.52, 2.1) and 1.4 (0.75, 2.5), respectively. However, the risk for intrauterine growth retardation was somewhat elevated among women with greater VDT use (OR = 1.6, CI = 0.92, 2.9). PMID- 2264567 TI - Chromosomal aberrations, sister chromatid exchanges, and urinary thioethers in nurses handling antineoplastic drugs. AB - In this study we examined the structural chromosomal aberrations (CA) and sister chromatid exchanges (SCE) of 12 nurses handling moderate quantities of antineoplastic drugs. Urinary thioethers were also measured to assess the potential exposure to alkylating drugs. Two control groups with similar mean age and smoking habits and working in the same hospital were also studied: 1) control clerks and 2) control nurses. Our study did not show any clear increase of chromosomal damage in exposed nurses as compared to controls. However, CA in control nurses were significantly increased (p = 0.05) with respect to control clerks. The results of baseline urinary excretion of thioethers were statistically higher (p less than 0.02) in exposed subjects than in control clerks. PMID- 2264568 TI - Solvent-associated decrements in olfactory function in paint manufacturing workers. AB - To assess the effects of low-level organic solvent exposure on olfactory function, a cross-sectional study in paint manufacturing workers was undertaken. Workers in two paint manufacturing facilities (N = 187) were tested using the University of Pennsylvania Smell Identification Test (UPSIT), a standardized, quantitative test of olfactory function. Industrial hygiene air samples over the past 13-15 years revealed that average solvent exposures in these plants were 2 40% of the existing threshold limit values for the three chemicals measured. Stratification by smoking status revealed evidence of dose-related decrements in olfactory function (p = .01) only in non-smokers. Furthermore, those nonsmoking workers in the highest exposure category had UPSIT scores below the fifth percentile for their age. These results suggest that solvents may cause nervous system dysfunction at lower levels than previously suspected, and that the olfactory system may be a critical target organ for the neurotoxic effects of solvents and other chemicals. PMID- 2264569 TI - Ventilatory dysfunction in glass bangle workers. AB - The pulmonary function status of 73 glass bangle workers suffering from chronic bronchitis having varied exposures to pulmonary toxicants in the work environment was evaluated in 1984. The findings were compared with those observed in 220 asymptomatic glass bangle workers and 88 unexposed controls. There was a higher prevalence (45.2%) of ventilatory dysfunction in the chronic bronchitic cases as compared to 19% in the asymptomatic workers and 2.3% in controls, respectively. The relative risk of airway obstruction was 8.3 and 19.6 times higher in the asymptomatic and chronic bronchitic workers respectively as compared to the controls (p less than 0.001). The prevalence of obstructive impairment among the smokers and non-smokers in the exposed workers was not statistically significant. However, age greater than 30 was found to be significantly associated with bronchial obstruction in chronic bronchitic cases. The relative risk of duration of exposure was found to be 1.86 in the asymptomatic workers exposed for more than 10 years (p less than 0.05) while it was 1.62 in workers with chronic bronchitis. The occupational and environmental factors responsible for the high prevalence of chronic bronchitis and associated ventilatory dysfunction in relatively young glass bangle workers are discussed. PMID- 2264570 TI - Organic acids and bases: review of toxicological studies. AB - Organic acids and bases are among the most frequently used chemicals in the manufacturing industries. However, the toxicology of only a number of them has been fully characterized, and for fewer still have occupational exposure limits been established. This paper reviews the acute and chronic toxicity data of the organic acids and bases, and considers the mechanism by which these chemicals produce their effects. A methodology for establishing preliminary occupational exposure limits based on the physicochemical properties of these chemicals is presented. Workplace exposure limits for 20 organic acids and bases which currently have no exposure guidelines are suggested. Advice regarding appropriate medical treatment of exposure to these materials is discussed. PMID- 2264571 TI - Aggressive non-Hodgkin's lymphomas in AIDS: the University of Colorado experience. AB - The authors performed this retrospective study to further investigate the relationship between non-Hodgkin's lymphoma (NHL) and the Acquired Immunodeficiency Syndrome (AIDS). From January 1984 through December 1987 all cases of AIDS and NHL diagnosed at the University of Colorado affiliated hospitals were identified and submitted to chart review. Twenty-five patients fulfilled criteria for the diagnosis of AIDS and 24 had biopsy-proven NHL, an additional patient met criteria for the diagnosis of primary central nervous system lymphoma and was included in the analysis. All patients had known risk factors for the development of AIDS. Of the biopsy proven tumors, 23 were categorized as high grade. Most patients (68%) presented with stage IV disease and 92% with extra nodal involvement. Median survival was 5 months and the cause of death was most often progressive lymphoma and/or opportunistic infections. These data are similar to previously published series. Clinical trials to evaluate effective treatment are warranted. PMID- 2264572 TI - Interaction of chloramphenicol and metabolites with colony stimulating factors: possible role in chloramphenicol-induced bone marrow injury. AB - We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10(-4) M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10(-7) M), nitroso-CAP (NO-CAP) (60% at 5 x 10( 6) M) and NPAP (35% at 10(-5) M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10(-6) M) and NO-CAP (5 x 10( 6) M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia. PMID- 2264573 TI - Chronic therapy for congestive heart failure with benazepril HCl, a new angiotensin converting enzyme inhibitor. AB - Benazepril HCl is an orally effective angiotensin converting enzyme (ACE) inhibitor previously shown to have significant acute hemodynamic benefits in patients with congestive heart failure. In this study, 21 patients with New York Heart Association Class III or IV congestive heart failure were treated with 2 to 15 mg of benazepril HCl as a single daily oral dose for 28 days to determine the clinical and hemodynamic value of chronic therapy. Each patient underwent clinical evaluation during the 28-day period, as well as invasive hemodynamic studies on the first two and last two days of the trial. Plasma ACE activity and aldosterone levels fell significantly and renin levels rose after therapy. Benazepril HCl produced significant (p less than 0.01) reductions in arterial pressure and systemic vascular resistance, with corresponding increases in cardiac output and decreases in pulmonary artery wedge pressure. Responses after 28 days of therapy were equivalent to those after the initial doses. Clinical effects included reduced rest, exertional and paroxysmal nocturnal dyspnea, as well as reduced peripheral edema. Only one patient developed symptomatic orthostatic hypotension. Thus, benazepril HCl, given once daily, is an effective and well tolerated oral agent for the chronic treatment of advanced congestive heart failure. PMID- 2264574 TI - Nitrogen metabolism in sickle cell anemia: free amino acids in plasma and urine. AB - Twenty-four hour urinary levels and fasting plasma concentrations of free amino acids (AA) were evaluated in adult sickle cell anemia (HbSS) and age-matched HbAA subjects with comparable daily energy (E) and protein (N) intake. HbSS elicited significant reduction in the sum of plasma indispensable (EAA) with no change in the dispensable (NAA) amino acids, resulting in a prominent (P less than 0.01) reduction in the EAA/NAA ratio from 71% to 55%. Arg (-38%), Leu (-32%), Val ( 28%) and His (-32%) were among the AA most severely affected. Despite a twofold increase in 24-hour urine volume in HbSS compared with HbAA subjects, total urinary losses of EAA and NAA were markedly reduced in the former group, with Arg (-53%) and Gly (-56%) levels most prominently affected. Compared with HbAA controls, HbSS subjects showed a three-fourfold increase in 24-hour urinary orotate excretion that had no relationship to amount of N intake. The results indicated that adult subjects with HbSS, who consumed adequate N and E as per the RDA for healthy individuals, behaved like normal HbAA controls on a low protein diet. There was evidence that the HbSS subject might be in a precarious state with respect to sufficiency of several amino acids, particularly L-Arg, which is now classified as conditionally indispensable for the human. PMID- 2264575 TI - Desmopressin-induced improvement in bleeding times in chronic renal failure patients correlates with platelet serotonin uptake and ATP release. AB - Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient. Hemorrhagic tendencies correlate best with laboratory tests of bleeding times. The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated. Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times. The multimeric state of the von Willebrand factor is also normal in these patients. The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP). No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment. However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment. These results indicate that DDAVP acts on the platelet membrane. This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion. Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times. PMID- 2264576 TI - 17 alpha-hydroxylase deficiency masquerading as primary hyperaldosteronism. AB - A unique case of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is reported. Initially the patient was misdiagnosed as testicular feminization for 16 years and was thought to have typical primary hyperaldosteronism for 5 years. However, careful detailed endocrine studies showed markedly elevated progesterone, deoxycorticosterone, and 18 hydroxycorticosterone values with low levels of 17-hydroxyprogesterone, 11 deoxycortisol, testosterone, and DHEA-Sulfate. In contrast to the suppressed aldosterone levels that are found in 17 alpha-hydroxylase deficiency, this patient's aldosterone levels were inappropriately elevated before and after ACTH stimulation. Use of glucocorticoid replacement resolved the patient's symptoms and completely corrected the hypokalemia and hypertension. In summary, recognition of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is important because hypertension, hypokalemia, and symptoms respond to steroid replacement. PMID- 2264577 TI - Kaposi's sarcoma involvement of the bone marrow. AB - Kaposi's sarcoma (KS) is a predominantly cutaneous malignancy with several clinical variants. Extracutaneous sites of involvement are uncommon in all disease variants except epidemic KS (human immunodeficiency virus related) and the African lymphadenopathic variant. Extracutaneous KS usually involves the lymph nodes, gastrointestinal tract, and respiratory tract. The authors report the first description of a patient with classic KS to have bone marrow involvement. Two additional patients with KS variants and bone marrow involvement have been described. Bone marrow tumor invasion should be considered in patients with KS and hematologic abnormalities. PMID- 2264578 TI - Schizophrenia and fatal self-induced water intoxication with appropriately diluted urine. AB - A 31-year-old woman with untreated chronic schizophrenia developed extreme polydipsia which rapidly led to coma and death due to cerebral edema. Hyponatremia (120 mEq/liter) and serum hypo-osmolality (260 mOsm/kg) were associated with marked polyuria (up to 1850 ml/hour) and appropriately low urinary osmolality (90 mOsm/kg) which responded to treatment. This case and few qualifying previous reports which are reviewed support the possibility that pure self-induced water intoxication with no major contribution of inadequate release of antidiuretic hormone may occur, and that extreme polydipsia can sometimes overwhelm normal renal diluting capacity in psychotic patients. PMID- 2264579 TI - Renal disease in noninsulin-dependent diabetes mellitus. AB - Diabetic nephropathy now accounts for approximately one-third of all patients who develop end-stage renal disease. The estimated cost to supply renal replacement therapy for this population now exceeds $750 million. The relatively recent realization that half of these individuals suffer from noninsulin-dependent diabetes mellitus has sparked increased interest in attempts to understand the pathologic processes involved and how they may be similar or different from those alterations seen in insulin-dependent diabetes mellitus. Basic and clinical investigation continues in an attempt to solve the puzzle of pathogenesis, as well as answer questions about the clinical usefulness of microalbuminuria and the appropriate management of hypertension in this population. PMID- 2264581 TI - Hyperosmolar states. AB - The composition of the extracellular fluid (ECF) must remain stable for cells to function properly. In normal individuals vasopressin and thirst zealously maintain the total ECF concentration, or osmolality, within a narrow range. Disruption of these regulatory mechanisms or rapid addition of solute to the ECF can lead to hyperosmolality. The serious neurologic symptoms that accompany many forms of hyperosmolality can be explained by understanding the physiologic response of cells to the osmotic stress. This review describes the physiology, pathophysiology, differential diagnosis, and therapy of hyperosmolar states. PMID- 2264580 TI - Can the rate of progression of chronic renal failure be altered? AB - The cost of renal replacement therapy for end-stage renal disease in the United States exceeds three billion dollars per year. Nonimmunologic mechanisms may contribute to progressive renal injury in renal failure of diverse etiologies. Based on the potential adverse renal effects of these processes, a number of dietary and pharmacologic interventions have been proposed as being potentially beneficial in slowing the rate of progression of chronic renal failure to end stage renal disease. This article reviews current evidence in animal models and humans supporting the efficacy of each of the proposed interventions. PMID- 2264582 TI - Pathogenesis of viral infections: the role of the immune response. AB - The replication and spread of viral infections in the human host occurs by a variety of mechanisms. Replication of genetic sequences varies with the initial starting material (DNA or RNA). Proliferation in the host may be by direct cell to-cell spread, cell lysis, or budding from the infected cell's membrane. Various viremic or localized stages have been demonstrated. Particular tropisms are thought to be due to the presence of particular receptors. Recent advances in molecular biology, which will be reviewed, have expanded our capacity to detect the genetic footprints of viruses, and our understanding of viral pathogenesis. The host immune system must be prepared for an array of mechanisms to prevent or ameliorate virus infection. These may take the form of specific and nonspecific antibody formation, or the generation of specific cytotoxic lymphocytes that are restricted by the HLA system. In addition, nonspecific mediators, such as the complement system, interferon, and other lymphokines, play a significant role in the pathogenesis of viral infections. While the greatest portion of these cellular efforts are aimed at the destruction or elimination of viral infection, the immune response may augment the pathogenic effect under some circumstances. The formation of immune complexes may also contribute to the pathogenesis of some infections. PMID- 2264583 TI - The free scapular flap for head and neck reconstruction. AB - The free scapular flap is a versatile flap for soft tissue and bony reconstruction of the head and neck. It has a very reliable blood supply and is easy to harvest. In this paper, we present our cumulative experience with the use of five cutaneous flaps and 31 osteocutaneous flaps. PMID- 2264584 TI - Thyroid gland flap for glottic reconstruction after vertical laryngectomy. AB - A thyroid gland flap was devised and applied in five cases of vertical partial laryngectomy to correct the laryngeal defect. The upper pole of the thyroid gland, dissected along with the superior thyroid artery and vein, was placed in the wound after removal of the tumor to compensate for the loss of bulk, and relined using a cervical skin flap. Good phonatory function was obtained without any disturbance of respiration or deglutition. The thyroid gland flap was adjustable to the size of the defect and easily placed in the larynx. Follow-up study for 6 to 18 months after the surgery revealed that the flap was less likely to shrink than the other flaps because of its abundant blood supply. PMID- 2264585 TI - Proton nuclear magnetic resonance spectroscopy of plasma lipoproteins in head and neck cancer patients. AB - Proton nuclear magnetic resonance spectroscopy was used to evaluate changes in plasma lipoproteins in patients with squamous cell head and neck cancer. Plasma from 14 patients was analyzed by proton nuclear magnetic resonance spectroscopy, and line widths and fast and slow methyl and methylene transverse relaxation values were obtained. In addition, the lipid and lipoprotein concentrations in the sera of these patients were measured by standard biochemical techniques. Preliminary results suggested that squamous cell carcinomas of the head and neck with nodal metastases are associated with measureable changes in slow methylene transverse relaxation values, as compared with controls. These findings indicate the presence of a new lipoprotein complex in patients with squamous cell carcinomas of the head and neck with nodal metastases. PMID- 2264586 TI - Detection of class II antigens on human nasal cartilage. AB - The presence and distribution of class II antigens on human nasal cartilage was investigated using monoclonal antibodies directed against HLA-DR, HLA-DP, and HLA DQ molecules. Tissue sections and chondrocytes in suspension were prepared for immunoperoxidase staining and flow cytometric analysis. Class II antigens were detected primarily on the perichondrium. In contrast, chondrocytes, either isolated or in tissue sections, were completely negative, suggesting that cells of the perichondrium, may, by themselves, be capable of initiating a rejection process. PMID- 2264587 TI - The dynamics of the vestibulo-ocular reflex in patients with vestibular neuritis. AB - The dynamics of the vestibulo-ocular reflex (VOR) were studied in 14 patients at the onset of vestibular neuritis, and at follow-up 1 year later. A velocity step stimulus of 150 degrees/s was used to investigate the VOR time constant and gain, and the results were related to the caloric response. In the acute, vertiginous phase of the disease, the VOR time constant was reduced but was almost normalized 1 year later, both among patients who regained normal caloric side-difference and among those who did not. However, the increase in VOR time constant was greater among those who regained normal caloric excitability, and regression analysis showed a correlation between the prolongation of the VOR time constant and the recovery of caloric excitability. These findings suggest that VOR dynamics are modulated during the acute phase of vestibular neuritis, and that there is recovery with vestibular compensation. Furthermore, the recovery of the VOR time constant is not solely dependent on the recovery of normal caloric excitability. This implies that central storage of velocity information may be involved in the VOR, even in cases of asymmetric vestibular input after vestibular compensation. PMID- 2264588 TI - Group C streptococcal sinusitis. AB - The group C streptococci have emerged as important human pathogens. A case of group C streptococcal sinusitis in a 6-year-old girl is reported and four cases of group C streptococcal sinusitis are reviewed. Age less than 18 years, central nervous system complications, and a delay in the institution of adequate therapy were features common to all five cases. Three patients were bacteremic with group C streptococci and two patients died. These cases suggest that when beta hemolytic streptococci are isolated from sinus culture, serogrouping should be performed. When group C streptococci are identified, appropriate antimicrobial therapy should be instituted and one should be alert for suppurative intracranial complications. PMID- 2264589 TI - Temporal bone histopathology: resident's quiz. Persistent stapedial artery. PMID- 2264590 TI - Fetal alcohol syndrome: current status of pathogenesis. PMID- 2264591 TI - Prenatal alcohol-induced brain damage and long-term postnatal consequences: introduction to the symposium. PMID- 2264592 TI - Neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects. AB - A clinical sample of 19 school-aged native children diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) was compared with age- and sex matched normal controls. Results on a battery of intellectual and neuropsychological tests indicated large and significant differences between alcohol-affected children and controls. FAS differed significantly from controls on measures of intellectual abilities, while FAE did not; FAS mean scores on these measures were significantly lower than FAE means. For neuropsychological measures, FAS were significantly poorer than controls on most measures, while FAE showed deficits compared with controls only on grip strength. The results suggest that neuropsychological measures would be a valuable supplement to intellectual measures for the purpose of assessing alcohol effects because they are less vulnerable than intellectual measures to the influence of cultural and educational experiences. PMID- 2264593 TI - Attention deficits in children exposed to alcohol prenatally. AB - Twenty children with fetal alcohol syndrome or fetal alcohol effect (FAS/FAE) were compared with 20 attention deficit disorder (ADD) children and 20 normal controls on three experimental tasks designed to isolate four different components of attention. Parents completed three questionnaires regarding their child's activity level and overall functioning, and the children completed a short form of an IQ test. The children in each group ranged from 5 to 12 years. Results indicate that although the children with FAS/FAE are significantly more impaired intellectually, their attentional deficits and behavioral problems are similar to those of children with ADD. These findings imply that the treatments known to facilitate learning in children with ADD may also benefit children with FAS/FAE. PMID- 2264594 TI - Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 7 1/2 years. AB - This longitudinal, prospective, population-based study examined the long-term effects of moderate prenatal alcohol exposure on 482 school aged children. Maternal reports of alcohol use obtained during pregnancy were significantly related to child IQ, achievement test scores, and classroom behaviors in second grade children, even after statistical adjustment for appropriate covariates. Consumption of two drinks per day or more on the average was related to a 7-point decrement in IQ in 7-year-old children even after statistically adjusting for appropriate covariates. Low paternal education and more children in the household were identified as environmental factors exacerbating the effect of prenatal alcohol exposure on child IQ. Learning problems were associated with the alcohol "BINGE" pattern of five or more drinks on at least one occasion. This study shows that alcohol use patterns within the social drinking range can have long lasting effects on IQ and learning problems in young school aged children. These patterns should not be interpreted as biologic thresholds. It should also be noted that these are group effects of prenatal alcohol exposure, not necessarily predictable in the individual child, and that for the most part these children were functioning within the normal range of intelligence. PMID- 2264595 TI - The long-term behavioral effects of prenatal alcohol exposure in rats. AB - Prenatal exposure to alcohol can cause a variety of behavioral disturbances later in life. Many of the reports in animals of the behavioral teratogenic effects of alcohol have focused on assessing younger animals. The purpose of this paper is to review some of the longer lasting behavioral consequences of gestational alcohol exposure in animals. It is not meant as a comprehensive review, but rather focuses on selected studies. It is concluded that prenatal alcohol exposure does have long lasting effects, although some of these might only occur under challenging or stressful circumstances. It is hypothesized that as the animal matures compensatory mechanisms or strategies develop to compensate for these dysfunctions. Thus, behavioral problems may only be detected when these compensatory systems break down, either as a result of stress, because of complex testing procedures, or old age. PMID- 2264596 TI - New approaches to research on the long-term consequences of prenatal exposure to alcohol. AB - As the summary presentation of a symposium on prenatal alcohol-induced brain damage and long-term postnatal consequences, this paper proposes the establishment of two main research priorities--to begin to correlate long-term behavioral effects with alterations in underlying neural substrates, and to explore the mechanisms of neuroteratogenicity. To reach these goals, three objectives are described. First, animal and human research must become more interrelated. Second, experimental observations should be integrated into formal models that incorporate both neural structure and function. Third, researchers should choose well-defined dependent measures that are derived from models of brain function based on modern concepts of cognitive neuroscience. Examples of neuropsychological tests that may serve as the bases for structure/function relationships are presented. Incorporating these objectives into future research will facilitate understanding of the fundamental issues concerning prenatal alcohol exposure and will begin to provide the bases for rational intervention or treatment. PMID- 2264597 TI - Utility of the Self-Administered Alcoholism Screening Test (SAAST) in schizophrenic patients. AB - The utility of the Self-Administered Alcoholism Screening Test (SAAST) in determining alcohol abuse and alcoholism was assessed in a preliminary study of 21 schizophrenic patients during their hospitalization in an acute care psychiatric unit; on admission all met DSM-III-R criteria for schizophrenia and none were detected to have any alcohol-related diagnosis. SAAST scores ranged from 2 to 26 with a mean score of 10.8. Forty-eight percent (10/21) had SAAST scores greater than or equal to 10, indicating "probable alcoholism"; 62% (13/21) scored 8 or higher. Every patient with a SAAST score of 8 or higher also met DSM III-R criteria for alcohol abuse or dependence on the basis of patient interview, independent chart reviews, and interviews of significant others. In contrast, only half (5/10) of the high SAAST scorers would actually admit to a problem with drinking during the extensive study interviews. Six SAAST items were found to be highly predictive of abuse or alcoholism; the SAAST had greater sensitivity than the interviews. Sixty-two percent (8 of 13) of the schizophrenic patients who met the DSM-III-R criteria for alcohol abuse reported a first degree relative with an alcohol-related problem, in contrast to only 25% of the "nonalcoholic" patients. The patterns of the alcoholic schizophrenic patients' responses on the different SAAST items revealed even greater denial and lack of insight than those of nonschizophrenic alcoholic subjects. PMID- 2264598 TI - Alcohol and secobarbital effects as a function of familial alcoholism: acute psychophysiological effects. AB - Previous research has demonstrated response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism. These response differences are thought to reflect differences in vulnerability to dependence on alcohol. Thus, the role of positive family alcoholism history in increasing risk of addiction to a variety of drug classes might be studied by determining whether FHP subjects show different responses to drug classes other than alcohol. This was done in the present study by determining dose-effect functions for a variety of physiological (heart rate, skin conductance, skin temperature), subjective (analog mood and drug effect, Subjective High Assessment Scale), and psychomotor measures (hand tremor, body sway, Digit Symbol Substitution Test, eye-hand coordination, and numeric recall) in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg by mouth) and ethanol (1 g/kg). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. At equivalent blood alcohol levels family-history positive subjects reported greater effects of ethanol than did family-history negative subjects on almost all subjective measures. Following the high dose of secobarbital, FHP but not FHN subjects showed elevated subjective effects; these effects were substantially less and were evident in fewer measures than following ethanol. In contrast to effects on the subjective measures, ethanol and secobarbital produced comparable impairment in both groups of subjects for most psychomotor responses. Group differences were not obtained on any physiological measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264599 TI - Sons of alcoholics report greater hangover symptoms than sons of nonalcoholics: a pilot study. AB - We investigated alcohol-induced hangovers among college men at high and low risk for alcoholism. Thirteen sons of alcoholics reported significantly (p less than 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics. The two groups reported comparable quantity-frequency of recent drinking. To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are "dependence-prone." PMID- 2264600 TI - A comparative blinded study in miniature swine of whole blood-, hemoglobin-, platelet-, plasma-, and lymphocyte-associated acetaldehyde as markers for ethanol intake. AB - Blood samples were obtained from miniature swine maintained on 0, 2, or 6 g/kg/24 hr ethanol for 8 months (N = 6 in each group). Samples from drinking pigs were taken after 8 hr of ethanol abstinence and all were coded and sent for "blinded" analysis. A fluorigenic high performance liquid chromatographic assay was used to quantify whole blood-associated acetaldehyde, hemoglobin-associated acetaldehyde, plasma-associated acetaldehyde, platelet-associated acetaldehyde, and lymphocyte associated acetaldehyde. Detectable levels of acetaldehyde were found in each sample in both drinking and nondrinking pigs. Analysis of whole blood-associated acetaldehyde was most discriminatory in distinguishing nondrinking from drinking pigs (mean 21.4 +/- 1.0 microM for nondrinkers vs. 24.6 +/- 1.5 SD for the group consuming 2 g/kg ethanol, p = 0.001). Measurements of hemoglobin-associated acetaldehyde normalized to protein concentration (250 +/- 47 nmoles/g vs. 203 +/- 33 SD, p less than 0.05 drinking vs. nondrinking pigs) and platelet-associated acetaldehyde (0.46 0.34 vs. 0.15 +/- 0.16 nmoles/3 x 10(8) platelets, p = 0.05 drinking vs. nondrinking pigs) were also useful in discriminating drinking from nondrinking animals. Analysis of plasma-associated acetaldehyde and lymphocyte associated acetaldehyde were not useful as markers of ethanol consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264601 TI - Taste reactivity in alcohol preferring and nonpreferring rats. AB - Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol. In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine. A two-bottle consumption test was then given for a 3-week period to allow the rats access to 10% alcohol. After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test. The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements. During the two-bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days. On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol. NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2. P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2. It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264602 TI - Subject selection bias in alcoholics volunteering for a treatment study. AB - Baseline differences in alcoholism problem severity were compared between alcoholics who did and did not volunteer to participate in a treatment effectiveness study. A positive relationship was found between self-reports of alcohol-related problems and the degree of research participation. Group differences were also revealed in the rate of treatment completion. Possible explanations and solutions for this volunteer bias are discussed. PMID- 2264603 TI - Alcohol abuse among grandsons of alcoholics: some preliminary findings. AB - Drawing upon self-reports of family history for alcoholism, the present study compared the level of alcohol abuse among grandsons of alcoholic maternal and paternal grandfathers. Although based on a small sample of grandsons (N = 29), the results indicated a significantly higher level of alcohol abuse among maternal compared with paternal grandsons. PMID- 2264604 TI - Effects of ethanol on hexose uptake by cultured rat brain cells. AB - The effects of ethanol on hexose uptake by glial cells was investigated using primary cultures prepared from term rat fetuses. Specific 3H 2-deoxy-D-glucose (2DG) uptake was significantly reduced by a 4-hr exposure to ethanol at concentrations of 25, 50, and 100 mM, but not 200 or 300 mM. The inhibitory effect of 50 mM ethanol increased with the duration of exposure, with 2DG uptake inhibited by 36% after 18 hr. Astrocytes cultured from the brains of term fetuses of rats fed ethanol during pregnancy showed essentially the same 2DG uptake response to in vitro ethanol treatment. Kinetics of 2DG uptake showed a significant decrease of Vmax in the presence of ethanol. No interaction was found between ethanol and insulin, which stimulated 2DG uptake and protein content of the cultures. The data suggest that ethanol can modulate hexose uptake by astrocytes cultured from fetal rat brain. However, insulin actions on glial cells were not affected by ethanol. PMID- 2264605 TI - Relationships between neuropsychological test performance and event-related potentials in alcoholic and nonalcoholic samples. AB - Are event-related potentials and nonconcurrently measured neuropsychological test performance correlated? Sober male and female middle-aged alcoholics and peer controls were administered an "oddball" event-related potential (ERP) task and several hours later, a battery of neuropsychological (NP) tests. Alcoholics performed significantly poorer than controls on NP tests. Male alcoholics had significantly altered ERP responses (N1, NdA, and P3 amplitudes) but female alcoholics did not differ on any ERP variables from controls. A number of significant correlations between ERP and NP measures were present. The most consistent findings were positive correlations between perceptual-motor (PM) tests and the P3 amplitude at Pz in both male and female alcoholics and in male alcoholics, a negative correlation between PM tests and P3 latency at Pz, findings similar to those seen in Parkinson patients. Significant correlations were most numerous in family history positive alcoholics. The results lead to two conclusions: first, Grant's postulation that sober alcoholics may manifest an intermediate duration organic mental disorder is supported; second, given the lack of ERP differences in the females, ERP measures should not be considered as being causally related to NP performance. PMID- 2264606 TI - Comparison of the Self-Administered Alcoholism Screening Test (SAAST) and the Khavari Alcohol Test (KAT): results from an alcoholic population and their collaterals. AB - This study examined the reports of patients and their collaterals on drinking practices, as measured by the summary scale of the Khavari Alcohol Test (the annual absolute alcohol intake, AAAI) and alcohol related behavioral patterns, as assessed by the Self-Administered Alcoholism Screening Test (SAAST). In- and outpatients from two Milwaukee area substance abuse treatment hospitals, and a number of their collaterals, participated in this study. Patients' and collaterals' responses on the AAAI and the SAAST were compared through the use of a paired t test. Results indicated no significant differences between patients' self-reports compared with collateral reports, and demonstrated a direct relationship on the AAAI (two tailed p less than 0.001) and SAAST (two-tailed p less than 0.001). Self-reports of patients who volunteered collaterals compared with self-reports of patients who did not volunteer collaterals also showed no significant differences on the AAAI or the SAAST, demonstrating consistency of reporting whether the patients believed their reports would be compared with information provided by a collateral or not. The AAAI and the SAAST corroborated in their diagnoses of patients as suffering from alcoholism (r = 0.515, p less than 0.001). Multivariate analysis revealed no significant effect of demographic variables on either the AAAI or the SAAST. This study shows: (a) impressive concordance between patient and collateral reports; (2) apparent intactness of memory, and little evidence of denial, as measured by the instruments; and (3) the efficacy of measures such as the AAAI and the SAAST, two vastly different scales measuring dimensions of alcoholism. PMID- 2264607 TI - The potentiating effects of ethanol on the blue light depolarization of the retinal pigment epithelium. AB - The retinal pigment epithelium (RPE) is the site of two major effects of ethanol. In humans, ethanol produces a slow damped oscillation in the steady electrical potential of the eye, which is generated primarily by the RPE. It has also been shown that ethanol potentiates the reversible, depolarizing effect of blue light on the transepithelial potential (TEP) of the isolated RPE. The present study demonstrates that in addition to the depolarizing effect of blue light on the TEP, a secondary, compensatory potential arises, which functions to maintain the TEP. The magnitude of the secondary response varies somewhat among preparations. It appears that ethanol eliminates or reduces the secondary, compensatory potential change which results in a large depolarization of the TEP when the RPE is irradiated with blue light. Microelectrode studies reveal that ethanol hyperpolarizes both the apical and basal membranes of the RPE with a greater effect noted in the apical membrane. This would account for the corneal positive potential elicited by ethanol in the human eye. Brief exposures (2-3 min) of blue light, after administration of 0.5% ethanol, results in a large (25-30 mV) depolarization of both membrane potentials as compared with 3 to 5 mV in untreated tissue. On the basis of our observations, it is hypothesized that some of the potentiating effects of ethanol in combination with other agents may result from an interference with a cellular adaptive response to impaired respiration rather than an additive effect on a common mechanism. PMID- 2264608 TI - Formation of the 37KD protein-acetaldehyde adduct in liver during alcohol treatment is dependent on alcohol dehydrogenase activity. AB - Protein-acetaldehyde adducts (protein-AAs) are formed in vivo during chronic alcohol ingestion. These protein-AAs reported thus far include a 37KD protein-AA in liver cytosol, cytP450IIE 1-AA in hepatic microsomes, hemoglobin-AA, and serum protein-AAs. It has been postulated that acetaldehyde or perhaps a reactive acetaldehyde radical generated by the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) explains the formation of the cytP450IIE1-AA. The source of acetaldehyde responsible for the formation of the cytosolic 37KD protein-AA has not been determined. In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein-AA in vivo and in vitro. It was found that feeding rats with an alcohol-containing liquid diet supplemented with cyanamide enhanced while a diet supplemented with pyrazole completely abolished the formation of the 37KD liver protein-AA. The liver of rats fed the pyrazole supplemented alcohol-containing diet showed significantly higher content of cytP450IIE1 than that of rats fed the diet containing alcohol alone. On the other hand, feeding the cyanamide supplemented alcohol-containing liquid diet did not further enhance the content of cytP450IIE1. Similarly, adding cyanamide to the culture medium enhanced while adding 4-methylpyrazole inhibited the production of the 37KD protein-AA by cultured hepatocytes even though the combination of alcohol and 4-methylpyrazole increased the content of cytP450IIE1 2-fold over that in control cells. These results demonstrate that the formation of the 37KD liver Protein-AA is dependent on ADH and not on MEOS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264609 TI - Pattern and duration of the inhibitory effect of alcohol administered acutely on suckling-induced prolactin in lactating rats. AB - We have characterized the pattern and duration of the inhibitory effect of acute alcohol administration on suckling-induced prolactin (PRL) release in the lactating rat. On day 2 of lactation, litters were adjusted to eight pups. On day 6, dams were implanted with an atrial catheter and experiments were conducted on day 10 of lactation. Pups were removed from the dams at 0800 hr. An extension tube filled with heparinized saline was attached to the catheter at 1300 hr. At 1400 hr, a preinfusion (PRE 0) blood sample was removed and was followed by infusion of saline (control) or alcohol in saline (0.5, 1.0, 2.0, 2.5 g/kg body weight doses) solutions. Following the removal of a postinfusion (POST 0) blood sample, pups were returned to the mother. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. In separate groups, the effects of alcohol on basal PRL were studied by collecting blood samples PRE 0, POST 0 and 20, 40, 60, 80, 100, and 120 min following infusion of saline or alcohol in saline to lactating rats also separated from their pups for 6 hr. Alcohol infusion did not alter basal PRL. However, suckling-induced PRL was inhibited at 10, 30, 60, and 120 min of suckling by alcohol administered at doses greater than or equal to 1.0 g/kg body weight. After 180 min of suckling, plasma PRL levels were comparable among groups. The suckling latency for the 2.5 g/kg body weight alcohol group was greater than for other groups, but the quantities of milk consumed during the 3-hr suckling period were comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264610 TI - Effects of acute alcohol intake on tolerance to hypotension. AB - The specific aim of this research was to test the hypothesis that intoxication with alcohol results in poor tolerance to hemorrhage. This was evaluated on the basis of blood pressure, cardiac output respiratory rate, blood flow to organs, and survival for 4 hr after hemorrhage. Four groups of six swine per group were used (control, intoxicated, hemorrhage, and intoxicated-hemorrhage). The results revealed that blood alcohol concentrations near 0.1% greatly reduced tolerance to hemorrhage. Intoxicated animals subjected to hemorrhage were unable to maintain an adequate cardiac output, blood pressure, or respiratory rate to sustain life. Pigs tolerated higher blood alcohol concentrations, up to 0.35%, when not exposed to hemorrhage. Also, unintoxicated pigs were able to compensate for severe hemorrhage. Only one of the six pigs in the intoxicated-hemorrhage group survived for 4 hr after hemorrhage. In conclusion the body's ability to compensate and recover from hemorrhage was greatly reduced during intoxication. It is logical to assume that the ability to overcome numerous other stressors may also be reduced during intoxication. PMID- 2264612 TI - Alcohol metabolism in men and women. PMID- 2264611 TI - Acute alcohol ingestion reduces fatty acid extraction of the heart, liver, and small intestine. AB - Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate. Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability. To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol. Fatty acid uptake was estimated with a 3 methyl substituted reagent with a chain length equivalent to 17 carbons. The methyl group in the three position prevented beta oxidation and prolonged the residence of fatty acids in the tissue. Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged. Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine. The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion. These alcohol effects were dose-dependent and temporally related. The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP). PMID- 2264613 TI - [Impotence]. AB - "Impotence" is a vague term for a variety of sexual dysfunctions in the male, such as libido disturbance, erectile impotence, dyspareunia and a number of ejaculatory problems. They are very rarely caused and maintained by any single factor. Usually a combination of organic and psychic factors is involved; the symptoms may give some indication as to what factors are dominant. Organic and surgical treatment should be considered cautiously and should have a clear indication. Frequent psychic causes are partnership or personality problems and the so-called vicious circle of performance anxiety. Sexual counselling is often all the therapy needed, especially when sexual knowledge is inadequate or when relative trivial partnership problems are involved. The kind of psychotherapy offered depends on the main problem: partner therapy, therapy directed at the control of personality problems, or therapy based on the Masters and Johnson method may be indicated. PMID- 2264615 TI - Albumin localization in the testis of adult golden hamsters by use of immunohistochemistry. AB - There is an increasing interest in different biochemical roles of albumin (Alb) in respect to testicular function. For this reason, Alb was localized by the peroxidase-antiperoxidase technique in the testis of adult golden hamsters. A strong Alb immunoreactivity occurred in the interstitial space and on the surface of Leydig cells. A few Sertoli cells showed a strong Alb response under the appearance of so-called leakages traversing Sertoli-Sertoli cell junctions. Spermatogonia reacted strongly, while spermatids and sperms showed rather a mild, or moderate response. Spermatocytes remained unstained. When similar maturation stages of seminiferous tubules were compared, the number of reacting cells varied strikingly. Our results support the assumption that Alb or a protein with an Alb like immunoreactivity exerts diverse functions of the testis. PMID- 2264614 TI - [Microbial flora in semen of infertile African men at Garankuwa hospital]. AB - This study was undertaken to determine the frequency of bacteria and Mycoplasmas in semen of infertile African men and to compare abnormal semen parameters with the presence of these organisms. Routine semen analysis were performed on 100 patients, and semen and first-voided urine samples were cultured. Mycoplasma hominis was cultured in 28% of seminal fluid and Ureaplasma urealyticum in 42%. These organisms were both present in 22% of cultures. Bacteriological cultures were positive in 6 urine and 21 seminal specimens. The frequency of tail abnormalities in the Mycoplasma positive group was greater as compared to normal values. From these it would appear that culture for Ureaplasma should probably be performed routinely at the Andrology Clinic. PMID- 2264616 TI - Pathogenesis of varicocele: experimental study using flow cytometric DNA analysis. AB - Despite extensive investigation, a cause-and-effect relationship between varicocele and male infertility has not been fully proven. We investigated the effect of a unilateral varicocele on both testes. Spermatogenesis in the rats with a surgically induced left varicocele was evaluated 5 weeks postoperatively by measurement of testicular weight, flow cytometric DNA analysis and evaluation of the mean seminiferous tubular diameter (MSTD). In rats with varicoceles, the testicular weight, the percentage of haploid cells and the MSTD were decreased in both testes in contrast to sham-operated rats. There was a greater decrease on the left side. These results suggest that unilateral varicocele may impair spermatogenesis in both testes, with the impairment being greater on the ipsilateral side. PMID- 2264617 TI - Effect of dihydrotestosterone on ultrastructural changes in rhesus monkey spermatozoa. AB - Dihydrotestosterone (DHT) was given at 10, 100 or 1000 micrograms per day for 70 days to adult male rhesus monkeys. Spermatozoa, collected by electroejaculation on days 21, 41 and 71 of treatment, were processed for spermiogram and Transmission Electron Microscopy. DHT, at all doses increased the number of spermatozoa showing coiled tails and the degree of coiling as well as ultrastructural changes. In the 10 micrograms group, on day 20 of treatment coiling of sperm tail was seen while 100 micrograms DHT induced additional changes like displacement of midpiece, loosening of plasma membrane over head region and increase in electron density of acrosomal region. Similar changes were seen only on day 40 in animals treated with 100 micrograms DHT. By day 40 - 70 of treatment, spermiophagy by macrophages was seen in all groups. PMID- 2264618 TI - [The presymphyseal corpus adiposum]. AB - In 35 male and 48 female cadavers always a "corpus adiposum praesymphysiale" was identified. By means of macroscopic preparations and plastinated crossections of human bodies in the regions of the mons pubis a flat flat-pad (corpus adiposum), covered by connective tissue, was found, which can be demarcated from the subcutaneous adipose tissue. This fat-pad shows a butterfly-like shape and in the male extends partially onto the funiculus spermaticus, while in the female reaches down to the labia majora. Cross and longitudinal diameters and the thickness of the praesymphyseal corpus adiposum were determined. PMID- 2264619 TI - [Cryopreservation of human spermatozoa--evaluation of 93 semen depots]. AB - Cryopreserved semen depots from 93 patients who had terminated contract with the CRYO-BANK-KREFELD were evaluated for prefreeze quality and post-thaw motility after a few days and after long-term storage (mean = 44 month). 2/3 of these patients had onkological disease. Only 20% of the ejaculates were normozoospermic and showed motility after thawing of more than 20%. The average recovery rate after long term storage was only 28% and revealed a significant decrease with time of about 20%. The concentration of motile spermatozoa, especially in patients with testicular cancer (x = 2.1 mill/ml), was so much reduced one must assume that in the most cases of semen banking there was no chance to achieve pregnancy. PMID- 2264620 TI - Active immunization with relaxin does not influence objectively determined sperm motility characteristics in rabbits. AB - Two groups of 5 rabbits were actively immunized with porcine relaxin or sham immunized. Serial analysis of sperm motion characteristics using the computer assisted Hamilton-Thorn Motility Analyzer over a period of 22 weeks did not reveal any significant antibody titers in serum and seminal plasma. In consideration of the present findings and after critical review of the literature it is concluded that an influence of relaxin on sperm motility is unlikely. PMID- 2264621 TI - Kallikrein therapy of infertile men with varicocele and impaired sperm motility. AB - A randomized group of 65 men with oligoasthenozoospermia and left side varicocele was subjected to a controlled study with kallikrein. Kallikrein (600 units orally per day) was given to 38 men for a period of 3 months. The other group of 27 men remained untreated but were followed up during the same period of time. After kallikrein treatment significant improvements in sperm quality could be observed: percentage of motile spermatozoa from 24.47 +/- 9.01 to 35.26 +/- 11.80, percentage of morphologically normal spermatozoa from 58.42 +/- 5.86 to 71.05 +/- 8.12. There was no improvement in sperm parameters in the untreated group of men. The results suggest that kallikrein therapy is useful for those men who refuse an operative or radiologic treatment of their varicocele and also as a primary or associated therapy of patients who underwent ligature or occlusion of spermatic veins. PMID- 2264622 TI - The involvement of surface sugars of mammalian spermatozoa in epididymal maturation and in vitro sperm-zona recognition. AB - The distribution of various simple sugar residues over the spermatozoa surfaces of five different mammalian species is characterized and compared. Epididymal maturation of the spermatozoa of all the five species studied exhibited an increase in the amount of N-acetyl-D-glucosamine residues over their acrosomal domains. A complete blockade of sperm-zona pellucida attachment of hamster gametes could be brought about when spermatozoa were treated previously with 0.1 M of N-acetyl-D-glucosamine. This sugar seems to be specifically involved in sperm-zona pellucida attachment in hamsters. The inter-specific cross-reactivity of gametes of laboratory mammals like rat, mouse, rabbit and hamster could, quite likely, be because of the involvement of N-acetyl-D-glucosamine as a common factor in this reaction in these animals. PMID- 2264623 TI - Presence of neuropeptide--Y and its C-terminal flanking peptide immuno-reactivity in the seminiferous tubules of human testis. AB - The presence of neuropeptide Y (NPY) and its C-terminal flanking peptide (C-PON) was described by immunohistochemistry in human testes. The immunopositive material was visualized in the spermatogenic elements of the seminiferous tubules. More NPY occurred in the younger testis and more C-PON in the older ones. NPY positive material was present mainly in the spermatogonia, and in the primary spermatocytes, where C-PON also occurred. The megalospermatocytes, present in aged testis, showed C-PON immunoreactivity. Both NPY and C-PON were present in granular form in the perinuclear zone of the cells. No positive material was detected in the Sertoli cells or in the Leydig cells. It is possible that NPY and its precursor are synthetized within the testis and might play a role in the paracrine and/or autocrine regulation of spermatogenesis. PMID- 2264624 TI - Vasopressin: another pregnancy protein in human seminal plasma. AB - Human vasopressin (arginine-vasopressin, AVP, antidiuretic hormone, ADH) was estimated, after protein precipitation and extraction in ethanol, using a new radioimmunoassay from Immuno Technology Service, Wijchen, Netherlands. Concentrations in human seminal plasma were 1.84 +/- 1.23 (0.6-4.1) pg/ml, estimated in good duplicates in all 20 samples, where 1 pg = 0.410 uIU/ml WHO 1st 77/501. This is about the same concentration as in blood serum, for which levels up to 8 pg/ml are found by the same kit. In contrast, only trace amounts of vasopressin were found in amniotic fluid at 16-22 weeks of gestation, with zero values in 8 of 19 samples, while another 9 samples showed zero in one duplicate and up to 0.46 pg/ml in the other duplicate, and one sample showed 0.09 pg/ml in good duplicates. PMID- 2264625 TI - Hypoosmotic swelling test in normo-, oligo-, astheno- and oligoasthenozoospermic men before and after swim-up separation of spermatozoa. AB - Semen samples from a total 58 men were examined by routine semen analyses and the hypoosmotic swelling test. Samples were classified as normal, oligo-, astheno- or oligoasthenozoospermic on the basis of spermatogram findings. The latter three groups showed a significant decrease in the percentage of HOS positive forms in comparison to normal spermograms. All these samples were treated with the swim up technique to select motile spermatozoa, using a procedure similar to that routinely employed in clinical settings for homologous intrauterine insemination (IUI). Following swim-up, the ejaculate supernatant and residual precipitate were subjected to the hypoosmotic swelling test (HOS test), and the percentage of normal forms was determined in the three groups. The results showed greater percentages of HOS positive, normal and HOS positive-normal forms in the group of normal individuals than in any of the other three groups. The supernatant used in IUI showed a significant increase in percentage HOS positive spermatozoa, normal forms and spermatozoa which were both normal and HOS positive in comparison with the other two groups in normal and oligozoospermic samples, but not in samples which presented suboptimal motility (astheno- and oligozoospermia). In conclusion, the swim-up technique is effective in separating high-quality spermatozoa in normo- and oligozoospermic samples, although its effectiveness with astheno- and oligoasthenozoospermic samples should be questioned. PMID- 2264626 TI - Absence of processus vaginalis in a stillborn twin with unilateral testicular retention. AB - A one day old full term twin boy presented with an abdominal left testis and a scrotal right testis both of which had a normal histological appearance. A gubernaculum with normal macroanatomy and histology was found in the left inguinal canal but no processus vaginalis could be detected. Both of his brother's testes were normally descended. It is suggested that the abdominal position of the left testis was caused by a failing gubernacular reaction due to a local hormone insensitivity. PMID- 2264627 TI - Different sperm velocity distributions in normozoospermic samples. PMID- 2264628 TI - The influence of relaxin on motility of human sperm in vitro. AB - Sperm of healthy men were incubated in an IVF medium with relaxin at concentrations of 3, 30, 300 and 3000 ng ml-1. Immediately after addition of relaxin and 60 and 120 min later motility, progressive motility, mean path velocity, mean progressive velocity, mean linearity and mean lateral head displacement were measured with the Hamilton-Thorn motility analyser. Neither immediately after relaxin addition, nor after 60 or 120 min, was an improvement of sperm motility observed at any concentration. PMID- 2264629 TI - [Katamnestic data on Turkish patients in the Department of Andrology between 1981 and 1984]. AB - In a katamnestic study we analysed both the clinical and spermatological data of 223 turkish andrological patients which has been investigated 1981-1984. Concerning the ejaculate parameters, mostly our findings corresponded to those of other authors. In 21.5% we found an azoospermia, in 43.5% oligozoospermia, 9.4% normozoospermia, 10.3% teratozoospermia and 9.0% asthenozoospermia. In 5.9% the patients were not able to produce a semen specimen for investigation. The sexual activity of turkish males is clearly higher than that of europeans. PMID- 2264630 TI - [Significance of linear cervix mucus penetration for the evaluation of spermatozoa quality]. AB - Linear mucus penetration of spermatozoa from 75 arbitrary selected men was evaluated using a non-commercial bovine cervix mucus preparation in the same way as Penetrak, but using round glass capillary tubes instead of flat plastic tubes. The mean penetration value was 28.7 +/- 7.10 mm in 90 min and the mean sperm density 36.0 +/- 22.79 x 10(6) ml. Mucus penetration was more correlated to sperm density (r = 0.6) than to any other semen parameter. Consequently it seems to be necessary to evaluate a sliding discrimination index for adequate penetration rate depending on sperm density (regression line and confidence interval). Numerical methods for comparison of penetration rates are suggested. PMID- 2264631 TI - [Mollicutes in male infertility: is antibiotic therapy indicated?]. AB - Mollicutes are frequently isolated from sperma of infertile men. The potential effect on the fertility of mollicute infection is controversial as is antibiotic therapy. In our andrological patients, the prevalence of mollicutes is approximately 10%. To evaluate the benefit of antibiotic therapy, we investigated two groups of patients: group 1-patients with positive or negative mollicute cultures and normal spermiogram; morphological changes on spermatozoa were particularly evaluated (n = 40); group 2 - patients with positive mollicute cultures treated with doxycycline or erythromycin. Sperm parameters were analysed before and after treatment (n = 20). When infected and non-infected sperma from group 1 were compared, the only difference found was an alteration of the sperm tail (p less than 0.005). Light microscopy and electron microscopy (EM) often revealed coiled tails which were probably due to adhesion of mollicutes (EM). The most frequently observed pathology in group 2 was found in patients with teratoasthenozoospermia. Compared with the post-therapy spermiogram, a significant difference was only observed in spermatozoal morphology (p less than 0.005). Therefore, we conclude that mollicutes produce important alterations in the human spermatozoal morphology, especially in the tail which appears in a spiral form. Since teratozoospermia is considered to be an important factor of infertility in man, antibiotic therapy is recommended in cases of mollicute involvement. PMID- 2264632 TI - Preservation of testicular tissue before fixation. AB - An optimum evaluation of testicular tissue for diagnostic purposes is only possible by means of the semithin-section-technique, which implies fixation in glutaraldehyde/OsO4 followed by embedding in Epon. Since in clinical departments adequate fixatives are not always available, various storage conditions until further processing were tested. Testicular tissues from 5 men, who underwent orchidectomy, were stored for different periods in solutions of Ringer, 0.9% NaCl, Macrodex, Dextran, 1640 Medium or in a humid chamber either at room temperature or at 4 degrees C, subsequently fixed and then studied by means of light and electron microscopy. Under most conditions, primary spermatocytes and Leydig cells disintegrated rather quickly, while spermatogonia, spermatids and Sertoli cells without fixation were relatively well preserved up to 5 hrs. For optimum preservation the storage of testicular tissue in a humid chamber at 4 degrees C is recommended. PMID- 2264633 TI - Morphology of seminal and swim-up spermatozoa and the outcome of in vitro fertilization and embryo transfer. AB - Tubal infertility was treated by in vitro fertilization-embryo transfer (IVF-ET) in 112 couples. Twenty-eight pregnancies were obtained in 140 treatment cycles. Couples are accepted for treatment in our IVF-ET programme if previous semen samples fulfil the inclusion criteria: ejaculate volume greater than 1.5 ml, concentration of spermatozoa greater than 15 x 10(6) ml-1, greater than 40% motile spermatozoa, and greater than 25% spermatozoa with normal morphology. In order to determine to which extent IVF-ET treatment results are influenced by sperm morphology, within this selected group of patients, we have retrospectively analysed the data from both original semen samples and swim-up preparations. The sperm morphology was not related to the outcome of treatment in terms of fertilization (ovum cleavage rate), early embryo development, or pregnancy. Nor was any relationship detected between early embryo development or pregnancy and the degree of improvement in morphology resulting from the swim-up procedure. However, if improvement in morphology by swim-up was high, ovum cleavage rate was low. Sperm morphology within the limits set by our inclusion criteria could not predict the outcome of IVF-ET treatment. It is further concluded that the presence of abnormal spermatozoa at the site of fertilization may be without harm if only the number of normal sperms is high enough. PMID- 2264634 TI - [Recommendations of the German Society of Andrology and the German Society for the Study of Fertility and Sterility regarding the support of andrology in Germany]. AB - Recommendations of "Deutsche Gesellschaft fur Andrologie" and "Deutsche Gesellschaft zum Studium der Fertilitat und Sterilitat" concerning the development as well as the future and the support of andrology in Germany are made. Furthermore, these proposals contain some aspects about the organization of a Department of Andrology or Andrological Units including a special program of training in clinical andrology as well as in basic research. PMID- 2264635 TI - Trends in cancer mortality in industrial countries. Introduction. PMID- 2264636 TI - Accuracy of cause-of-death certification in Hiroshima and Nagasaki, Japan. PMID- 2264637 TI - Cancer mortality trends analysis for Bologna and province. Programs, methodology, objectives, and early results. AB - The scenario, the organization, the activities and the objectives of the Cancer Registry of Bologna and Province are presented. The first available data on mortality in 1986-1988 show (1) that the mortality due to malignant tumors represented in 1988 31% of the whole mortality in Province; (2) that the mortality due to tumors is higher in males and in the urban area (35.73% of the whole mortality in 1988); (3) that the mortality due to malignant tumors is increasing, particularly amongst males; and (4) more than 40% (amongst males) and nearly 50% (amongst females) of the whole mortality below 70 years of age is due to malignant tumors. PMID- 2264638 TI - Multinational trends in cancer mortality rates. Methodological issues and results. AB - Identification of trends in cancer mortality rates for specific sites is useful both for targeting areas of health concern and for suggesting topics where epidemiologic research into etiology might be fruitful. Differences and similarities across countries may provide clues for further research. Counts of cancer mortality by sites are often considered as Poisson processes. Using this framework, Poisson regressions can be used to identify time trends. Model identification can also be difficult and is aided by the graphical techniques of exploratory data analysis. Plots of the data can identify the existence of trends, nonlinearities, cohorts with special risks, and artifacts due to such things as ICD revision. Because human perception is often distorted by outliers in the data, local nonparametric smoothing can yield more robust plots for model identification. Quasi-likelihood methods can be used to incorporate serially correlated and overdispersed covariance structures. These techniques are illustrated using cancer mortality data from selected industrialized countries. PMID- 2264639 TI - Lung cancer and smoking trends in the United States over the past 25 years. PMID- 2264640 TI - Changes in non-smoking related lung cancer with special reference to mortality trends in Swedish women. PMID- 2264641 TI - Lung cancer not attributable to smoking. PMID- 2264642 TI - Some notes on brain tumor epidemiology. PMID- 2264643 TI - Is brain cancer mortality increasing in industrial countries? AB - This paper analyzes recent age-specific trends in brain and other central nervous system cancer mortality from 1968 to 1986-1987 in the United States, United Kingdom, Italy, France, and West Germany. It also examines changes in the use of diagnostic confirmation technology in the U.S. SEER program from 1973 to 1987 to estimate the influence of such factors on recent mortality trends. Other sources of error have not been evaluated in this paper. In the United States and Sweden, deaths due to brain and other central nervous system cancer, adjusted to the overall population, are unchanging. However, age-specific analyses of brain and other nervous system cancer in six major industrial countries show markedly different trends at different age groups, with drastic increases in brain tumor rates in the old: rates doubled in persons ages 75 to 84. In the United States, microscopic or radiographic confirmation occurred throughout this time period in 96% of all incident cases of brain and other central nervous system cancers diagnosed before death in the SEER program, with older persons receiving consistently more radiographic tests than younger persons. The use of diagnostic technology may change over time and across populations, but it is not known to what extent it accounts for these increasing trends, which require careful additional study. PMID- 2264644 TI - International time trends for multiple myeloma. PMID- 2264645 TI - Multinational trends in multiple myeloma. AB - Reported mortality rates from multiple myeloma have been increasing in all industrialized countries in the last 20 years. The rate of increase shows a strong interaction with age: it is slow in persons aged 55 to 59, and increases steadily with increasing age to reach rates of increase in excess of 4% per year in persons 85 years and older. The rate of increase is moderately consistent across sexes and countries. Multiple myeloma is one of the best ascertained cancers, which argues against better ascertainment as the sole cause of the increasing trend. Cohort plots in the United States suggest a parallel shift upward in risk between the birth cohorts of 1870 and 1910, with no evidence of differential effects in the elderly. This suggests a real increase is occurring as a result of some general environmental factors. PMID- 2264646 TI - Is exposure to benzene a cause of human multiple myeloma? PMID- 2264647 TI - International trends in cutaneous melanoma. PMID- 2264648 TI - Patterns of melanoma deaths in the United States. PMID- 2264649 TI - Lifestyle and trends in worldwide breast cancer rates. PMID- 2264650 TI - The Israeli breast-cancer anomaly. PMID- 2264651 TI - Mortality trends for leukemia in selected countries. PMID- 2264652 TI - Analyses of changes in the ratios of male-to-female cancer mortality. A hypothesis-generating exercise. AB - Site-specific cancer trends are particularly useful indicators to identify cancers that should be subject to further case-control research to identify causes of the rate changes. One of the most sensitive of trends is that of the ratio of male-to-female rates, especially by age groups. This ratio is likely to eliminate rate changes due to better diagnosis, treatment, and cancer ascertainment. Also some lifestyle changes may be eliminated by considering the male-female ratio as they equally affect both genders. On the other hand, some may produce substantial effects. The finding of large increases in male-female cancer mortality ratios at specific sites in the United States and in all cancers, except lung, in several countries suggests that case-control studies of some sites are worthy of consideration to identify the gender-related differences. Because most male rates are increasing relative to females, any case control study should certainly include occupational factors among those investigated. PMID- 2264653 TI - Decline in death rates among asbestos insulation workers 1967-1986 associated with diminution of work exposure to asbestos. PMID- 2264654 TI - Register epidemiology studies of recent cancer trends in selected workers. AB - The Swedish Cancer Environment Register (CER) was used to analyze occupational risks of cancer over time. Using expanded time coverage (1961-1984) and two census-based sources in employment information, risk in the work environment was evaluated for a 24-year period for pleural mesothelioma, nasal adenocarcinoma, and non-melanotic skin cancer. Standardized incidence ratios (SIRs) for pleural mesotheliomas were found to increase among plumbers and pipefitters over this period, whereas those for mechanics, electricians, painters, and paperhangers remained relatively stable. Risk for nasal adenocarcinoma among cabinet makers remained exceedingly high over the 24-year period and SIRs for other kinds of woodworkers moderately increased during the same time. Excess skin cancer risk among physicians declined over the period. Reasons for these trends are discussed as well as the limitations and potential of register epidemiology in the evaluation of cancer trends in the work environment. PMID- 2264655 TI - Cesium-137/potassium-40 ratios in firewood ashes as a reflection of worldwide radioactive contamination of the environment. PMID- 2264656 TI - Death from all cancers. Trends in sixteen countries. PMID- 2264657 TI - International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and the United States. PMID- 2264658 TI - Competing causes of death. A review of recent trends in mortality in industrialized countries with special reference to cancer. AB - In most industralized countries, the last two decades or so have been characterized by a further significant reduction in mortality. Summary measures of mortality, such as the age-standardized death rate, have declined in parallel with reductions in CVD mortality. Yet, cancer mortality over all ages has risen in the majority of industralized countries. However, this rise in cancer mortality has been accompanied by a rise in the average age at death from the disease, suggesting further progress in deferring death. How much of the observed increase in cancer mortality for such sites as the brain, as well as for multiple myeloma, is real is difficult to determine. Certainly, for countries such as the United States, where mortality from ill-defined causes and ill-defined cancer sites has not fallen, it is quite probable that the increase in death rates largely reflects a real increase in cancer risk. There can be little doubt that the rise in lung cancer mortality is a real trend and this has repeatedly been shown to mirror, with an appropriate lag period, previous changes in cigarette consumption. On the other hand, for some countries, such as France, Japan, and Italy, there have been very substantial postwar declines in mortality rates from ill-defined causes, and hence any increase in mortality from diseases for which diagnostic precision is known to have improved must be viewed with some caution. The reductions in CVD mortality have also been accompanied by a rise in the average age at death and a decline in the proportion of all deaths attributable to CVD. There have thus been fewer CVD deaths and these deaths are increasingly postponed to higher ages. This is reflected by the widespread decline in summary indices of premature mortality, such as the age-standardized death rate at ages 35 to 74 years. On the other hand, cancer death rates at these ages have risen in several countries, suggesting that at least some of the "younger" persons "saved" from dying from CVD are now succumbing to cancer. The suggestion that previous cigarette smoking has "claimed" the majority of "saved" lives from CVD is supported by the evidence on mortality trends for major sites of cancer. (The principal site of the disease for which mortality in males at ages 35 to 74 years rose in most countries substantially is lung cancer, which accounts for the vast majority of the rise in overall cancer mortality where it has occurred.) These conclusions would be strengthened if one could demonstrate parallel trends based on incidence data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2264659 TI - International study of time trends. Some methodological considerations. PMID- 2264660 TI - Effect of changes in cancer classification and the accuracy of cancer death certificates on trends in cancer mortality. PMID- 2264661 TI - Simultaneous superior oblique sheathectomy and inferior oblique tuck in congenital Brown's syndrome. AB - Since Harold Brown, in 1950, described the superior oblique tendon sheath syndrome, numerous surgical techniques have been explored to treat this condition. Tenectomy of the homolateral superior oblique, alone or in combination with a weakening procedure on the homolateral inferior oblique, has been the technique most advocated. However, good functional results are rarely achieved in a single procedure, and delayed complications are frequent. Taking advantage of the improved dissection and reduced trauma afforded by the use of a surgical microscope, one of the techniques first recommended and later abandoned by Brown was reappraised. The technique consists of dissection of the sheath and attachments of the superior oblique, while preserving its tendon, combined with a 10mm tuck of the homolateral inferior oblique. Both a typical and a severe atypical congenital case, according to the classification of Brown, were treated in this fashion. Full correction was achieved in both. PMID- 2264662 TI - Herpes zoster ophthalmicus and iris cysts. AB - Herpes zoster ophthalmicus has been associated with numerous complications such as neuropathy, keratitis, anterior uveitis, and neuralgia. To my knowledge, there have been no reports of secondary iris cyst formation. I hereby report the case of a patient who developed an iris cyst during a Herpes zoster ophthalmicus infection. PMID- 2264663 TI - Blunt ocular trauma secondary to "war games". AB - "War games" are gaining popularity in the western United States. These recreational contests involve members of one team attempting to shoot their opponents with high-velocity dye or paint pellets fired from air guns. Unfortunately, serious eye injuries occur when participants do not use protective eye wear. We report a case of severe blunt ocular trauma resulting in a hyphema, choroidal rupture, and retinal and vitreal hemorrhage secondary to a paint pellet striking an unprotected eye. This injury resulted in a significant visual defect in this patient. PMID- 2264664 TI - Aphakic visual fields by automated perimetry. AB - Accurate testing of the visual field of aphakic patients is demanding due to the optical distortion induced by high plus corrective lenses. This testing procedure can be improved by using an aspheric contact lens instead of a full-aperture loose trial lens. We found that the contact lens enhances the ability of the pattern-deviation printout of the Statpac analysis to identify glaucomatous visual field abnormalities in program 30-2 of the Humphrey Visual Field Analyzer. PMID- 2264665 TI - Childhood blindness in Peru. AB - A survey of childhood blindness in Peruvian children was done. Although most causes of blindness were due to congenital and hereditary conditions, measles accounted for almost 10% of blindness. With widespread measles immunization, this preventable cause of blindness in children can be eliminated or dramatically reduced. PMID- 2264666 TI - Multiple orbital tumors were cavernous hemangiomas. AB - Two distinct masses in the left orbit were incidentally found in a 48-year-old woman during a computed tomographic scan done to evaluate neurologic complaints. Initial diagnostic considerations focused on a lymphoproliferative disorder or other systemic disease. Orbitotomy revealed two discrete tumors, both cavernous hemangiomas. Although uncommon, cavernous hemangioma should be considered in the differential diagnosis of the patient with multiple orbital lesions. PMID- 2264667 TI - Effects of hyaluronic acid fractions in the rabbit eye. AB - Two fractions of hyaluronic acid with different molecular weight (Ial, molecular weight 500,000-730,000 and Healon, molecular weight 750,000) were injected intracamerally or intravitreously in the rabbit eye. Although the fraction with higher molecular weight caused an increase in intraocular pressure, no change of this parameter was found after administration of the fraction with the lower molecular weight. Furthermore, various inflammatory reactions in ocular tissues were observed during slit-lamp biomicroscopy after administration of Healon but not of Ial. No inflammatory reaction was found after subchronic instillation of the compounds. PMID- 2264668 TI - The predictability of infant visual-evoked response testing on future visual acuity. AB - We reviewed the records of 27 infants with abnormal eye examinations and visual evoked response (VER) testing (mean age, 10.5 months) who subsequently underwent a long-term follow-up ophthalmology examination (mean duration, 41 months). The infants were initially diagnosed with various ocular disorders including cortical blindness (eight), optic nerve hypoplasia (six), congenital cataract (two), and retinopathy of prematurity (one). Standard optotype visual-acuity determinations were available in the follow-up records of 11 children (21 eyes), and fixation behavior was obtained in the remaining 16 children (32 eyes). Results revealed that pattern-reversal VER P1 latency was predictive (87%) of whether visual acuity was equal to (or better than) or worse than 20/100 and whether a patient would have good fixation behavior (fix and follow, FF) or poor fixation (no FF) (86%) (P less than .001). Although flash VER P1 latency was also predictive of later visual acuity or good fixation (73%), it was not statistically significant. Pattern VER P1 amplitude and flash VER P1 amplitude were not predictive of later visual function. The predictive power of pattern VER P1 latency for later visual function probably relates to its reflection of macular function and low variability. An analysis of the variability of each of the four VER factors in normal infants (n = 50) indicated that pattern VER P1 latency was the least variable, and consequently most sensitive, VER factor for detecting and quantifying pathology. Overall, the results of this retrospective study suggest that pattern VER P1 latency may have important predictive power for later visual function in infants with an initially abnormal ophthalmologic examination. PMID- 2264669 TI - Plasmodium: resistance to antimalarial drugs. AB - Quinine-resistant Plasmodium falciparum was first reported in 1910 from Brazil. Today this parasite is resistant in most endemic areas to the widely used blood schizonticide, chloroquine. Many strains are resistant also to antifols (e.g. pyrimethamine, proguanil) and some are also no longer eliminated by quinine. These polyresistant parasites have an enhanced ability to resist also new drugs such as mefloquine and halofantrine. There are indications that P. vivax is also becoming resistant to chloroquine in Papua-New Guinea where primaquine resistance of the hypnozoites also exists. The modes of action of antimalarials and mechanisms by which parasites become resistant to them are discussed. Future developments include the search for radically new compounds, for drugs that reverse chloroquine resistance and for new strategies to impede the progress of this problem. PMID- 2264670 TI - [Recent achievements and perspectives in medical entomology and vector control]. AB - High technologies of molecular biology and genetics, supported by computer use brought considerable advances in taxonomy, physiology, host/parasite relationships, ecology and epidemiology. New insecticides, IGR and bacteria are now available. Both simple methods (e.g. tsetse trapping, impregnated bednets) and large programs using heavy material (e.g. O. C. P. in West Africa, mosquito control in Northern hemisphere) have been successful. Guineaworm control lies in an intermediate position. Malaria control has difficulties and needs new tools and a better use of those already existing. A few progresses are noticed in biological and genetical control. Appropriate structures, well trained and motivated personnel, adequate funding and political willingness are the keys for the implementation of any control programme. PMID- 2264671 TI - [Antisense oligonucleotides: tools of molecular genetics and therapeutic agents]. AB - The binding of an oligodeoxynucleotide, so-called anti-sense, to the complementary sequence of a messenger RNA can prevent the synthesis of the encoded protein. This approach constitutes a very efficient and specific means to artificially regulate gene expression. Numerous chemical modifications have been introduced into synthetic oligos in order to provide them with properties that unmodified molecules do not display. For instance, oligos built up with methylphosphonate, phosphorothioate and alpha-anomer units lead to molecules that are resistant to DNases. Acridine-linked oligos exhibit an increased affinity for the target sequence due to the intercalation of the dye into the oligo/RNA duplex. Two different mechanisms account for translation inhibition by antisense oligos. Inhibition of the elongation step results only from the induced cleavage of the target RNA by RNase-H. In contrast, oligos targeted upstream of the AUG initiation codon can block the initiation step through an RNase-H independent mechanism. As a consequence, methylphosphonate- and alpha-oligos, which do not elicit RNase-H activity, targeted to the 5' region, are efficient antisense; but they are inactive if targeted to the coding sequence. Experiments performed with antisense oligos in cell-free extracts supported the notion that the mini-exon sequence, acquired by trans-splicing, was present on every message in trypanosomatids and on some of them in nematodes. Furthermore, an acridine-linked oligo complementary to the mini-exon sequence of Trypanosoma brucei induced a lethal effect on cultured procyclics. Therefore these compounds constitute promising tools in molecular genetics and could open new routes to rationally tailor therapeutic agents. PMID- 2264672 TI - Biotechnology as applied to vectors and vector control. AB - Vector borne diseases remain some of the major public health problems in the developing world. In this review some of the current applications of biotechnology to vectors and vector control and some of the possible future applications are discussed. PMID- 2264673 TI - [Impact of vector control on the aquatic environment]. AB - Environmental impact of pesticides used in vector control programmes against Onchocerciasis, Trypanosomiasis, Malaria and Bilharziasis, depends on chemicals used and control strategies. Dealing with the experience of the Onchocerciasis control Programme in West Africa, we introduce in what perspective, it is possible to establish an environmental monitoring programme in order to minimize the impact of treatments. In tropical Africa, vector control chemicals pressure, decreased in the years 1980. PMID- 2264674 TI - [Candidiasis: molecular basis of parasitic adaptation of opportunistic pathogenic protists]. AB - Candida albicans is a versatile organism living as a commensal of the gastro intestinal tract and having the ability to invade host tissues and to initiate serious diseases under the appropriate environmental conditions. The molecular basis for adherence, invasion, interactions with specific and non-specific immune factors have been studied in parallel to structural characteristics of the yeast. The main parasitologic features are closely linked to phenotypic variations. In this respect, mannoproteins are strongly involved in the cell wall variations. The study of the oligomannosidic repertoire represents one of the essential steps for the understanding of host-parasite relationships. PMID- 2264675 TI - Genetic aspects of malaria parasite infection and the host immune response in relation to parasite evasion. AB - In relation to problems found up to now for the development of vaccines against malaria, recent studies have pointed out the different strategies evolved by the parasites to evade the host immune response. They include antigenic variation, antigenic polymorphism, antigenic mimicry and direct interference with the generation of the host immune response. These different mechanisms are rapidly reviewed and discussed with the aim of focusing the actual orientation of basic and applied research which has been developed to overcome these difficulties. PMID- 2264676 TI - Sexual stages in trypanosomes and implications. AB - The basis for concluding that a system of genetic exchange exists in African trypanosomes of the Trypanosoma brucei group is outlined by the accumulated data from variation in natural parasite populations and from laboratory crossing experiments. The results indicate that these parasites can complete their life cycle either with or without genetic exchange. This sexual event involves meiosis and syngamy, but the order of these processes and the sexual stages involved are not yet known. PMID- 2264677 TI - The Syphaciinae (Oxyuridae, Nematoda) parasitic in rodents and lagomorpha. Numerical taxonomy. Cladistic analysis of evolution. AB - Two different methods are successively used for the systematic study of the Syphaciinae, a parasitic group of pin-worms specific for the Rodents and Lagomorpha. The statistical method permits to build a "phenetic classification"; the cladistic method permits to build a "phylogenetic classification". The classification finally proposed is principally found on the results of the morphological study of the parasites, but has also in view the integration of all available data concerning the biology, the biogeography and the phylogeny of the hosts. PMID- 2264678 TI - Haplodiploidy in the Oxyurida: decoupling the evolutionary processes of adaptation and speciation. AB - Host distribution and life history variation in the Oxyurida are discussed in the context of haplodiploidy. The Oxyurida have the broadest host distribution of any zooparasitic nematode group but have retained a virtually unchanged life cycle. Like other haplodiploids, oxyuridians have life histories that maintain viscous population structures. It is postulated that this has facilitated speciation but may have discouraged major evolutionary innovation in the group. PMID- 2264679 TI - The life-cycle of Leishmania in the sandfly with special reference to the form infective to the vertebrate host. AB - A review is given of recent advances in studies on the life-cycles of leishmaniae in phlebotomine sandflies including observations on the morphology and attachment of the parasites, putative genetic exchange in Leishmania, newly found factors affecting the development of the parasite in the fly, and the characteristics of metacyclic promastigotes related to their preadaptation for life in the vertebrate host. PMID- 2264680 TI - [The future of parasites]. PMID- 2264681 TI - Morbidity and mortality from parasitic disease in the year 2000. PMID- 2264682 TI - [Opportunistic parasitic diseases in Africa. Clinical aspects and diagnosis]. AB - Opportunistic parasitic infections are diagnosed more and more often in African patients with AIDS. Cryptosporidiosis is the most frequent with a prevalence between 7 and 31%. The prevalence of Isospora belli is between 5 and 19% and that of strongyloidiasis between 2 and 5%, depending on the authors. These parasitic infections are probably one of the frequent causes of chronic diarrhea in Africa. The prevalence of toxoplasmosis and pneumocystosis are not well known. (Between 5 and 17% for toxoplasmosis and 29% for pneumocystosis). The diagnostic technics used are those currently known. Toxoplasmosis and pneumocystosis seen in these patients have the same presentations as those in developed countries. PMID- 2264683 TI - [Antigenic variation of African trypanosomes]. AB - Although several hundred of different antigen genes exist in the trypanosome genome, only one is usually expressed at a time. This expression occurs in one of several possible telomeric expression sites. Besides being exclusively telomeric, transcription of the antigen gene exhibits other particular characteristics: the RNA polymerase is highly resistant to alpha-amanitin, and the transcription unit comprises several other genes, one of which may encode an adenylate cyclase. Post transcriptional controls modulate the activity of this transcription unit during the parasite life-cycle. Antigenic variation is achieved through either alternative activation of different expression sites, or gene recombination within a given expression site. These mechanisms ensure a relative programming of antigen expression. PMID- 2264684 TI - [Where do the parasites of man come from?]. AB - The Hominids have come in contact, over the last few million years, with the infective stages of many parasites which had up to then evolved in non Primate hosts; this is because Hominids have occupied multiple environments and acquired diversified behaviour. The high number of these lateral transfers explains the multiplicity of current human parasitic diseases whereas their youth on an evolutionary scale accounts for the seriousness of most of these diseases. The basic questions arising from the exceptional opportunities offered to parasites by the evolution of the human lineage concern: the precise role played by human behaviour, the mechanisms of alterations in specificity, the identity of the original host phyla, the dynamic and genetic consequences for parasites, the relationship with the evolutionary history of the ancestors of Homo sapiens sapiens; for instance, it is suggested that man's mastery of fire, allowing him to cook his food, dramatically reduced his contamination by certain parasites and that this contributed to the subsequent success of Hominids. PMID- 2264685 TI - Deep water parasites. AB - Few geographically local comprehensive studies on deep-sea parasites have been done. A recent study of parasitism in midwater fishes conflicts with broad generalizations previously advanced. Surveys of demersal fishes and macrofaunal invertebrates in the North Atlantic indicate 1) there is little evidence of coherence and continuity of faunal zones around the ocean basin and 2) that the community concept should be abandoned because faunal assemblages only persist on a local scale. Parasitological evidence supports this view. The implications are that the parasite species distributions and character of parasite faunas will vary according to the distribution of the fishes and local faunal assemblages. PMID- 2264686 TI - Competition, contacts, and other factors restricting niches of parasitic helminths. AB - Mechanisms that restrict the intraintestinal niches of helminths (as indicated by the sites they occupy) can be favored by several selection pressures. These selection pressures act on different scales, and may interact to have different effects in different circumstances. In addition, the end results may not reflect responses to the niche, but be a by-product of other processes, such as the immune responses of the host. PMID- 2264687 TI - [Gastrointestinal strongylosis and malabsorption of nutrients]. AB - The role of malabsorption of nutrients in the mechanism of reduction in productions of the ruminants infested with gastrointestinal nematodes has been a controversial question because of the compensatory absorption and reabsorption in distal part of the small intestine. However, during the last decade, leading research showed that malabsorption has a major role in this mechanism because of 1) compensatory absorption and reabsorption remain limited to some nutrients, 2) large quantities of incompletely digested nutrients exceeding the intestine capacity, and 3) poor reutilization of reabsorbed nutrients. PMID- 2264688 TI - Parasitism in young animals. AB - Pulmonary and gastrointestinal helminthiasis in young ruminants is usually followed by the development of immunity and lifelong freedom from disease. However, the recent advent of very effective systems of anthelmintic prophylaxis during the first year of life poses questions about the degree of immunity which animals might be expected to possess in later life. Aspects of this are discussed and, since bovine dictyocauliasis is potentially the most serious, the possibility of immunisation of older cattle, rather than calves, is suggested. PMID- 2264689 TI - Parasitic zoonoses: selective review of some diseases in South America. AB - Selected parasitic zoonoses which occurs in South America are discussed with emphasis on epidemiology, diagnosis and control of echinococcosis, taeniosis/cysticerosis and lagochilascariosis. PMID- 2264690 TI - [Molecular probes in the study and diagnosis of parasitic diseases]. AB - Molecular biology techniques have contributed, in the last ten years, to a better understanding of parasitic diseases. DNA probes, for example, have been successfully used not only for taxonomic purposes, but also for the diagnosis, the epidemiology and the pathogenicity of these infections. Due to their high sensitivity and specificity, the DNA probes allow, from a diagnostic point of view, the detection of very few of parasites in a given sample. This detection is also valid for any parasitic stage considered. It can be specially used to detect the infective stage in the vector, which, in epidemiological studies, is very important. The identification of parasitic species or sub-species indicates the human infectivity of species considered in the past as zoophilic. Finally, by allowing the specific identification of strains, isolates or even particular clones, the DNA probes also show differences which can be related to pathogenicity, to particular biological characteristics, or even to drug sensitivity. In this review, I relate the main results obtained in malaria and toxoplasmosis in our laboratory in Grenoble. I will also consider some recent data on amoebiasis, leishmaniasis, trypanosomiasis, filariasis, schistosomiasis and echinococcosis. PMID- 2264691 TI - [The slow progress in the control of sleeping sickness]. AB - The century-old controls methods of T. gambiense infection foci have not been changed significantly in the past decennias. The technical improvements are restricted to (1) the introduction of serological diagnosis bringing a marked gain in sensitivity as compared to lymph node palpation, (2) new parasite concentration methods for corroborating the diagnosis and (3) the design of cheap and efficient traps for glossina. None of these methods however, although smooth to perform and plain in design, is easily applied in the field conditions where T. gambiense is transmitted. Progress in the molecular biology of the trypanosome has been booked in the last few years, but it does not yet bring about a change in the active detection and the treatment of the patients and parasite carriers. PMID- 2264692 TI - New approaches in the diagnosis of Taenia solium cysticercosis and taeniasis. AB - Taenia solium cysticercosis is now recognized as a priority in Mexico and a number of other developing countries, both in public health and in economic terms. Recognition of the problem has been greatly aided in recent years by new developments in molecular diagnostics. In this paper data are presented on ELISA for the detection of anti-cysticercus antibodies and of parasite antigens in patients with neurocysticercosis and in cysticercotic pigs. Also, several biological fluids were evaluated: cerebrospinal fluid (CSF), serum and saliva, all of which have proved useful. CSF is, however, the most appropriate for detection of antibodies and antigens in patients and serum in pigs. In addition, saliva may be especially used in epidemiological surveys. The electroimmuno transfer blot technique (EITB) for antibody detection in patients and pigs has also proved highly sensitive and due to the use of an enriched fraction of glucoproteins, EITB is also highly specific. Cloned cDNA sequences from T. solium are now being assessed as an alternative source of antigens for immunodiagnosis. Two methods for the diagnosis of the adult stage of T. solium are also undergoing standardization. These are an ELISA for the detection of parasite antigens in fecal samples and DNA hybridization techniques for the detection of eggs in stools. Both assays have promising results and should now be assessed in larger numbers of clinical and epidemiological samples. PMID- 2264693 TI - Studies of the mode of action of anthelmintic drugs: tools to investigate the biochemical peculiarities of helminths. AB - An overview is given of the results from mode of action studies which improved our knowledge of some biochemical and/or electrophysiological aspects of parasitic helminths. Studies of the molecular mechanism of action of for example, antimonials, piperazine, levamisole, ivermectin, salicylanilides, praziquantel, benzimidazole carbamates, oxamniquine and hycanthone offered tools to learn more of the parasites and their hosts. PMID- 2264694 TI - [Anxiety disorders in children: do any risk factors exist?]. AB - Anxiety disorders in children are currently undergoing reclassification. On the basis of a review of the literature, the authors have attempted to point out the main evidence suggesting that a number of risk factors are associated with childhood anxiety disorders. Age and sex seem to influence the risk of anxiety disorder. The child's personality is of central importance: studies of the concept of "temperament" carried out in recent years have underscored that inhibition and introversion in early childhood are associated with an increased risk for anxiety disorders in later childhood. A low socioeconomic setting also seems to be a risk factor whose incidence varies across types of anxiety disorder. Familial risk factors have a very strong effect: children of parents with current or past anxiety disorders with or without mood disorders are at increased risk for anxiety disorders; this risk varies according to the type of disorder in the parents (for instance, the respective roles of panic attacks and avoidance behaviors remain unclear). Lastly, comorbidity is also an important factor: most children with anxiety disorders also have one or several other anomalies, usually anxiety or mood disorders. PMID- 2264695 TI - [Asymptomatic urinary infections in children]. AB - Asymptomatic urinary tract infection is diagnosed on the usual criterion used for urinary tract infections in children (at least 10(5) organisms per ml). There are no clinical manifestations. These asymptomatic infections are due to organisms with little infective potential and no harmful effects on the urinary tract or renal parenchyma. In patients with no malformations of the urinary tract, antimicrobial treatment is unnecessary. PMID- 2264697 TI - [An unusual germ causing a limp: Eikenella corrodens]. AB - A case of retroperitoneal appendicular abscess due to Eikenella corrodens is reported. This facultative anaerobe is normally found on the respiratory and intestinal mucosa and may be responsible for opportunistic infections. Culture is difficult and growth is slow. There have been few previous reports of the localization reported herein. A limp was the first manifestation of the infection. The differential diagnosis and pathophysiology of this symptom are discussed. PMID- 2264696 TI - [Fatal cerebral and pulmonary aspergillosis in acute leukemia in a child]. AB - Immediately after induction therapy for acute lymphoblastic leukemia, a 2 1/2 year-old child developed invasive pulmonary aspergillosis revealed by pneumothorax, an unusual manifestation. Despite treatment with amphotericin B, status epilepticus occurred; this manifestation was related to diffuse ischemic cerebral lesions probably caused by cerebral aspergillosis. Outcome was fatal. Early invasive pulmonary aspergillosis is responsible for non-specific pneumonia. Thoracic CT scan and fiberoptic bronchoscopy are informative investigations. At recovery of bone marrow aplasia, the occurrence of hemoptysis and the discovery of excavated lesions on roentgenograms are suggestive of the diagnosis. Cerebral aspergillosis should be routinely considered whenever neurologic symptoms develop in a patient with agranulocytosis, fever, and pneumonia. The prognosis of invasive aspergillosis depends above all on the promptness of treatment; amphotericin B should be given intravenously whenever broad spectrum antimicrobial therapy fails to induce apyrexia in a patient with agranulocytosis. PMID- 2264698 TI - [Waldenstrom's hyperglobulinemic purpura. Apropos of a case]. AB - The authors report the case of a thirteen-year-old girl who developed clinical manifestations suggestive of Schonlein-Henoch purpura and in whom biologic tests outruled this condition and led to the diagnosis of Waldenstrom hyperglobulinemic purpura. Investigations illustrated the immunologic nature of this disease, outruled an underlying disease and established the diagnosis of primary hyperglobulinemic purpura. PMID- 2264699 TI - [Gastroduodenal ulcers in children in Cameroon. Apropos of 28 cases diagnosed by endoscopy]. AB - This study was undertaken to describe the epidemiology and clinical features of peptic ulcer in children on the basis of twenty-eight endoscopically documented cases. Mean age was 11,5 years (range 4-16 years). Twenty-five percent of patients had a positive family history for peptic ulcer and 32% had risk factors. Two-thirds of patients had abdominal pain, occasionally accompanied with bleeding. Duodenal ulcers were slightly more common (15 versus 13). The ulcer was chronic or primary in seventeen cases, whereas endoscopic findings showed that eleven cases were acute or secondary. PMID- 2264701 TI - [Intestinal obstruction caused by a pacifier]. AB - The case of an infant who developed intestinal obstruction following ingestion of a pacifier is reported. Progression of this foreign body in the intestinal lumen was extremely slow because of the deformability of the material and laparotomy was required. The authors point out that this is a difficult diagnosis and that regulations on manufacturing standards should be enforced in order to avoid such accidents. PMID- 2264700 TI - [The preventive treatment of recurring respiratory infections using RU 41740 in 3,008 children]. AB - Biostim is an immunomodulating agent of biologic origin indicated for the prophylactic treatment of recurrent respiratory tract infections in adults and children over one year of age. It has been proved effective by double-blind placebo-controlled trials. This study was undertaken to evaluate the value and tolerance of Biostim in a large number of patients under the conditions of actual use. Three thousand and eight patients were included in the study. At inclusion, 93.7% of patients had a history of recurrent ENT infections (6.27 +/- 3.04 episodes during the previous year). After three months follow-up, results were considered good by the investigator in 75.8% of cases; 75.3% of the children had either no infection or only one infection during the three months follow-up. Results were not influenced by age and/or a history of allergy. PMID- 2264702 TI - [Physical and biophysical aspects of high energy intracardiac electrical discharges. II. Correlations between the physical and electrical effects of liminal and infraliminal shocks]. AB - The electrical phenomena produced during the fulguration impulses are analyzed using a digital oscilloscope which enables the calculation, with precision, of the energies consumed all along the curve or between chosen times. Moreover, it enables the calculation of the corresponding impedance values and shows that the latter varies during all the discharge. The explanation for these impedance variations is obtained thanks to rapid cinematography, showing the formation of the fulguration bubble. Hence, one can observe an impedance variation which is quite distinctive from the one which would correspond to the simple passage of an electrical current in saline solution. Particularly at the end of the impulse, an important increase in the impedance corresponds to the loss of ionization of the bubble. Therefore, by simply reading these electrical parameters, it is possible to know the main stages of the fulguration phenomenon for impulses situated around the deflagration threshold. PMID- 2264703 TI - [Elaboration of an ethogram for the diagnosis of the A Pattern in coronary pathology]. AB - In order to develop a technique which allows the detection of Pattern A (PA) we present in this paper a series of steps for constructing an observation gril (ethogram) which allows for the quantification of behavior in situation of structured interview. The behavioral units making up the final ethogram are derived from inter-item correlations taken from a population of 48 subjects who had suffered heart attacks. The observations on this population permit an inclusion score in the PA. These observations also confirm that the PA present a risk factor which is independent of classical risk factors. A significative positive correlation with work stress has been found showing, in accordance with the view of Friedman and Rosenman that the PA corresponds to a particular behavioral pattern which is dependent on the work environment. PMID- 2264704 TI - [Myocardial infarction in patients aged 70 years and over]. AB - 109 subjects aged 70 years (58 women, 51 men; average age 77 years) were hospitalized in the CICU (Cardiology Intensive Care Unit) over the period stretching from 1984 to 1986. The average length of stay in the CICU was 1 week, completed by an average stay of 5 days in the cardiology department. 100 per cent of the patients were followed up. Of the clinical parameters made evident by this study, the authors note that hypertension was the predominant risk factor (52.2 per cent); a history of coronary disease was noted in 60.5 per cent; 26.6 per cent of the patients were hospitalized before the 6th hour, chest pain being typical in 78 per cent versus painless in 11 per cent of patients; topographically, the infarction was anterior in 55 per cent, posterior in 40.4 per cent, and around the circumference in 4.6 per cent of cases; 80.8 per cent of the infarctions were transmural versus 19.2 per cent of infarctions without the Q wave--the latter accounted for a higher hospital mortality rate (38 per cent versus 27.3 per cent). The main complications were disturbances in rhythm (60.6 per cent) and LVI (56.9 per cent). Complications on the form of infections were noted in 15.6 per cent. Apart from the usual indicators of severity (cardiogenic shock, VF, LVI), infarction of the RV and AF had a serious effect on the prognosis. latrogenic disease accounted for 18.9 per cent. From the point of view of prognosis, hospital mortality was 30 per cent; mortality after one year was 44 per cent and 47.7 per cent after 2 years (in a group of 76 subjects).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264705 TI - [Non-ruptured calcified aneurysm of the Valsalva's sinus with angina pectoris and aortic insufficiency. Surgical treatment]. AB - We report a case of aneurysm of the straight frontal, and not coronary, aortic sinus, non ruptured and calcified, responsible for a refractory angina pectoris and a massive aortic failure in a 71 year old woman. The surgical treatment consisted in the exclusion of the aneurysm of the aortic sinus by a tubular prosthesis in which only two thirds of the circumference have been used, associated with the replacement of an aortic valve by a bioprosthesis, without associated coronary by-pass. PMID- 2264706 TI - [A rare cause of acute circulatory failure with pulmonary edema: catecholergic cardiomyopathy of pheochromocytoma]. AB - We report the case of a 37 years old woman with pheochromocytoma of the adrenal gland, with acute circulatory failure and pulmonary oedema. Its originality lies, besides the rare circumstances of diagnosis, in the echographic aspect of the left ventricle with an apical myocardial infarction with both severe apical hypokinesia and compensating basal hyperkinesia. In the literature the most frequent aspect of catecholamine cardiomyopathy is a large uniform dilatation of the left ventricle with often wall hypertrophy. After surgical ablation of the left adrenal gland tumor, we observe quickly a complete normalisation of the picture and especially the echocardiogram. The cardiomyopathy and the pulmonary oedema can result from the specific action of the excess catecholamines on the myocardial cells and the pulmonary capillaries. PMID- 2264707 TI - [Repair of post-infarction interventricular communication in a 81-year-old patient]. AB - Post-infarction interventricular fistula (IVF) is a complication with a poor prognosis, particularly when it occurs very early after myocardial necrosis, when it is wide in diameter and even more so if it is at a posterior site, and if there are associated lesions which require surgery. An operation is often considered as contraindicated in cases where the patient is elderly. The authors report on the case of an 81-year-old diabetic patient operated for a wide post infarctus posterior IVF and aorto-coronary artery bypass surgery. The operation is still a clinical success after 23 months of follow-up, showing that old age is not an absolute contraindication for surgery in cases of post-infarction IVF. PMID- 2264708 TI - [Phosphodiesterase inhibitors]. AB - Phosphodiesterase III inhibitors constitute a new therapeutic group for congestive cardiac failure. They inhibit the degradation of cyclic adenosine monophosphate and increase the intracellular calcium. They have a double inotropic and vasodilator haemodynamics occurs without any increase in the myocardial effect. The improvement in the consumption of oxygen. The beneficial haemodynamic effect seems to last over a medium period of time, but the survival in the long term treatment is not yet known. PMID- 2264709 TI - [Benign tumors of the heart (excluding myxoma). Experience with 9 surgically treated cases]. AB - Benign non myxomatous cardiac tumors are rare. Between 1968 and 1988, 9 patients presenting benign non myxomatous cardiac tumors were operated in our institution. Tumors were: 2 rhabdomyomas, 2 lipomas, 2 fibromas, 1 pheochromocytomas, 1 mesothelioma and 1 papillary fibroelastoma. Total excision was possible in all cases but one (multiple fibromas). We hereby present a review of the literature on the subject. We focalize on the new imagery techniques in order to help the diagnosis and on the new surgical possibilities (cardiomyoplasty) which make possible complete surgical excision. PMID- 2264711 TI - New challenges for parathyroid surgery. PMID- 2264710 TI - [Comparative study of the mid-term electrocardiographic and clinical tolerability of bepridil versus diltiazem in patients with coronary disease]. AB - A randomized, double-blind, multicentric study has been carried out to compare the electrocardiographic tolerance and the clinical benefit of bepridil (B) (300 to 500 mg/day) and of diltiazem (D) (180 to 300 mg/day). 227 patients with stable coronary disease, aged 70 years or less (mean = 59.4 +/- 7.2 years) have received treatment (116 B vs 111 D) during 16 weeks. The standard ECGs at each visit (D 0 inclusion-, D 14, D 28, D 70, D 112) show that, in group D, 9 first degree auriculo-ventricular blocks (ABV), occur during the study while no ABV occur in group B. A significant prolongation of the QTc (+5%) is observed as from D 14 in group B patients compared to those in group D. This difference persists during all the study. The study of Holters of 24 hours, carried out on D 0, D 70 and D 112, shows the good tolerance of B in this type of population. The number of patients presenting attacks of angina, the frequency of these attacks and the amount of TNT consumed are not different for the two groups under treatment, whatever the period studied. The frequency of extracardiac and cardiovascular undesirable effects is not different for the two groups. The number of patients who left the trial is not different for the two groups. The biological tolerance remained within normal limits in both groups. The analysis of the individual data has never shown any pro-arrhythmic effect, attributable to B or D, in the patients with no initial arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264712 TI - Mortality in patients surgically treated for primary hyperparathyroidism due to solitary adenoma. AB - In a multicentre study including 5 surgical departments in Europe and USA the results of surgical treatment in primary hyperparathyroidism (HPT) due to single adenoma were analysed. At long term follow-up 60 out of 282 patients operated on for solitary parathyroid adenoma were found to be dead. The average age at operation was 69.2 years and the time of survival after surgery 3.9 years. The cumulative relative survival in patients aged 60-64 years was reduced by 18% (P less than 0.01) as compared to a control group corrected for nationality, age and gender. In patients above the age of 65 no such reduction could be demonstrated. The operative mortality was 1% and attributed to cardiac failures. Late mortality was caused by cardiovascular conditions in 52% and by malignant disease in 15%. None of these figures were statistically different from the age, gender and nation corrected control group. Among the miscellaneous causes of death were two patients who committed suicide during the first postoperative year. The results indicate that surgery for parathyroid adenoma can be performed with low morbidity and mortality. PMID- 2264713 TI - Microangiographic changes of the pancreatic ducts in experimental chronic pancreatitis. AB - Chronic pancreatitis was induced in eight piglets by dividing all pancreatic attachments to the duodenum. Five piglets served as controls. The animals which were operated on were autopsied six weeks thereafter. Ductography and microangiography were performed. Histological preparations of pancreatic tissue were made. All of the animals which underwent operation developed histologically verified chronic pancreatitis. Ductography revealed the main ducts and the side branches to be considerably dilated. They also exhibited variations in calibre and sudden obstructions. Two animals had a large non-infected pseudocyst. No communication between the cyst and the main duct could be demonstrated by ductography. No pancreatic calcifications were seen. The vasculature of the ductal plexuses seems to be derived from interlobular arteries. The animals with chronic pancreatitis had marked diminution of the vascular supply of the ducts. The changes in ductal vascularity correlated with the severity of the histological changes to the pancreas and may, thus, in part explain the progress of pancreatitis. PMID- 2264714 TI - Absorption of bile acids after ileoanal anastomosis. AB - Absorption of bile acids was investigated using 75Se-homotaurocholate (SeHCAT) in 27 patients with ileoanal anastomosis and J-pouch, 7 patients with conventional ileostomy and 9 non-operated patients with ulcerative colitis. Retention of SeHCAT at seven days was higher in non-operated patients than in patients with ileoanal anastomosis (P less than 0.001) or conventional ileostomy (P less 0.01). There was no difference in retention of SeHCAT between patients with ileoanal anastomosis or conventional ileostomy. Malabsorption of bile acids was not associated with changes in blood chemistry or faecal fat excretion. Patients with ileoanal anastomosis and low retention of SeHCAT had more severe villous atrophy of the pouch mucosa than those with high retention (P less than 0.05). In conclusion, both patients with ileoanal anastomosis and conventional ileostomy have impaired absorption of bile acids when compared with non-operated patients with ulcerative colitis. In patients with ileoanal anastomosis, impairment of bile acid absorption is related to villous atrophy of the pouch mucosa. PMID- 2264715 TI - Diverticulitis of the colon: role of surgery in preventing complications. AB - Fifty-seven patients who were treated conservatively for colonic diverticulitis between 1977 and 1979 were followed for at least 10 years. Twenty-four patients had two or more episodes of diverticulitis, but only three had surgery on a prophylactic basis because of recurrent attacks. None of the patients had any serious complications during the follow-up. During the same period, eight patients with inflammatory pseudotumour underwent elective sigmoid resection and primary anastomosis without complications. --Between 1977 and 1988, forty-eight patients had emergency surgery for septic complications of diverticulitis. The mortality was 17%. Only two patients had had one episode of diverticulitis before the actual emergency. Recurrent diverticulitis rarely causes complications that may need emergency surgery. On the other hand, serious complications of diverticulitis usually are the first clinical manifestation of the disease. Thus, the chances of preventing complications with active prophylactic surgery seem to be limited. PMID- 2264716 TI - Double-contrast barium examination and endoscopy in the detection of small polyps of the large intestine. AB - The purpose of this study was to compare double-contrast barium examination (DCBE) and endoscopy in detection of small colonic polyps. In 57 patients DCBE revealed 106 polyps in the large intestine. On total colonoscopy, 62 polyps could be verified. The size of the polyps excised ranged from 2 to 15 mm. Compared with DCBE, colonoscopy verified 48 true positive, 44 false positive and 14 false negative polyps. In revealing a polyp less than 5 mm, DCBE had a sensitivity of 72%, whereas in detection of larger polyps the sensitivity was 81%. Histological verification was available in 52 of the 62 removed polyps. A tubular adenoma was found in 12 of the 29 diminutive polyps verified with histology. DCBE and colonoscopy could not differentiate between adenomas and hyperplastic polyps. Since a polyp less than 5 mm may represent an adenoma, a precancerous lesion, its removal is indicated during colonoscopy after DCBE has detected it. PMID- 2264717 TI - Shoulder function after prosthetic replacement of proximal humerus. AB - Between 1973 and 1985 eighteen patients with bone tumours and two patients with comminuted fractures had their proximal humerus replaced with a custom made isoelastic hemiendoprosthesis. In 1987 a clinical and radiographical review was performed of eleven patients with a mean follow up time of seven years, range 3 10 years. Four patients had pain at rest and six patients experienced severe pain on exertion. Active range of motion was poor and constituted only half of the corresponding range of passive motion. Shoulder girdle muscles were generally weak, only one patient could keep the arm straight in a flexed or abducted position. All patients had returned to their previous occupations, but their ability to perform ADL functions was poor. Rotator cuff insufficiency was considered to be the major cause of poor shoulder function. In comparison to most other surgical alternatives in tumour cases endoprosthetic replacement of the proximal humerus appears to be a safe and reliable method. The endoprosthesis gives stability to the arm and normal elbow and hand function is preserved. PMID- 2264718 TI - Removal of osteosynthesis material from healed hip fractures. Indications and prognosis. AB - Many patients complain of pain after their hip fractures have healed. We tried to determine if it is possible, on the basis of radiographic findings and pain localization, to select the patients who will improve if the osteosynthesis material is removed. In 39 instances (34 patients) hardware was removed because of pain. These patients were interviewed and their radiographs reviewed. In 23 instances the pain was lateral, in 4 in the groin and in 12 in both locations. Complete or very considerable alleviation of pain was seen in respectively 16, 2, and 7 of the patients in these groups after osteosynthesis material removal, in 22 within three months. Seventeen patients had pathological radiographic findings before removal. No consistent association was detected between these findings and pain localization. Four out of nine with segmental collapse of the head of the femur were improved by removal. A number of these had had only lateral pain. Of the ten patients where the hardware protruded laterally into the soft tissues, eight improved. Three of these had only groin pains. Pain localization is a poor indicator of the value of osteosynthesis material removal. Perhaps more patients should be offered removal. This may also apply to those with some segmental collapse of the femoral head. PMID- 2264719 TI - Girdlestone operation. An acceptable alternative in the case of unreconstructable hip arthroplasty. AB - Between 1970 and 1984, 1250 total hip arthroplasties using methylmethacrylate bone cement were performed at the Department of Surgery, University of Turku, Finland. Girdlestone arthroplasty was performed in nine women and one man in ten cases of failed arthroplasty. In general, the results were evaluated as good. The patients were satisfied, and they had no pain or only slight or occasional pain on weight bearing. Nine of ten patients could walk, two of them without any walking aids. In conclusion, the Girdlestone operation can offer an acceptable functional result when reconstruction of the hip joint is not possible. PMID- 2264720 TI - Cubital nerve block vs haematoma block for the manipulation of Colles' fracture. AB - Blocking efficacy and acute toxicity of prilocaine (15 ml of 10 mg/ml prilocaine) was examined in 35 (16 + 19) patients by using blocks of the radial, ulnar and median nerves in the elbow region (Group 1), or the haematoma block method (Group 2) for the manipulation of Colles' fracture. In Group 1 vs Group 2, the reposition was painless in 44% (7/16) vs 68% (13/19), moderate pain occurred in 38% (6/16) vs 21% (4/19), and severe pain in 19% (3/16) vs 11% (2/19). At 15 minutes there was a higher degree of block, on average, at the median and ulnar nerve innervation areas in Group 1. Complete motor block at peripheral innervation regions of all three nerves was achieved in only one patient in Group 1 and in no case in Group 2. Despite this, the surgeons assessed the relaxation at the wrist satisfactory for reposition of the fracture in all but one patient (Group 2). The highest individual prilocaine plasma concentration in Group 1 was 0.68 microgram/ml at ten minutes, whereas the highest individual value in Group 2 was 0.77 microgram/ml at ten minutes. Systemic toxicity from the local anaesthetic did not occur. PMID- 2264721 TI - Electrophoretic protein patterns of Geotrichum and its teleomorphs. AB - Total patterns of water-soluble proteins of 35 strains (7 species) of Galactomyces and Dipodascus strains with their respective Geotrichum anamorphs are compared. Quantitative differences among a number of species are found with iso-electric focusing; bands that characterize species are selected. Qualitative differences are found between the teleomorph genera. PMID- 2264722 TI - Inhibition and killing of fungi by the polyamine oxidase-polyamine system. Antifungal activity of the PAO-polyamine system. AB - Both components of the polyamine oxidase (PAO)-polyamine system are known to be present in phagocytes and have thus been postulated to contribute to the antimicrobial activity of these cells. Therefore, the effects of the PAO polyamine system on three medically important opportunistic fungi were examined. Yeasts of Cryptococcus neoformans, but not Candida albicans blastoconidia or Aspergillus fumigatus conidia, were efficiently killed by the system. Two putative end products of the system, hydrogen peroxide and acrolein, both killed C. neoformans at concentrations attainable with the whole system. However, catalase failed to inhibit activity of the whole system, making hydrogen peroxide an unlikely mediator of killing. Although C. albicans blastoconidia and A. fumigatus conidia were not killed by the PAO-polyamine system, germ tube formation by the former, and hyphal growth by the latter, were markedly inhibited. These data establish that the PAO-polyamine system possesses antifungal activity. PMID- 2264723 TI - Kurtzmanomyces tardus sp. nov., a new anamorphic yeast species of basidiomycetous affinity. AB - A new yeast species of basidiomycetous affinity Kurtzmanomyces tardus was isolated from contaminated demineralized water. It differs from K. nectairii, the only other Kurtzmanomyces species so far described, in its carbon assimilation pattern and low DNA-DNA homology (2.3% +/- 2.1). PMID- 2264724 TI - Chitin synthetase activity in a developmental mutant of Phycomyces blakesleeanus. AB - Chitin synthetase activity was analyzed in vitro and in vivo in two morphogenetic stages, namely, dormant spore cells and germlings of the wild type strain and the developmental mutant S356 of Phycomyces blakesleeanus. In vitro experiments showed a much higher specific activity in dormant spores of the mutant strain than in those of the wild-type. This difference was restricted to the dormant spore phase since germlings exhibited comparable levels of activity to those detected in the wild-type strain. Although no correlation was observed between chitin synthesis in vitro and in vivo in mutant spores, germination of these cells was accompanied by an earlier expression of chitin synthetase in vivo. Germination of mutant spores in liquid medium produced morphologically aberrant germlings. Contrary to the extended mycelial growth of the wild-type strain in solid medium, the mutant grew with a typical colonial morphology. Results are discussed in relation to the possible basis of the mutant phenotype. PMID- 2264725 TI - Chemical analyses, local Shwartzman reactivity, and body weight-decreasing activity of aqueous-phenol extracts of Mycoplasma salivarium cells. Biological activities of Mycoplasma salivarium. AB - Aqueous-phenol extracts of Mycoplasma salivarium ATCC 23064 cells (APM) showed demonstrable differences from lipopolysaccharides (LPSs) of Veillonella rodentium ATCC 17743. These were as follows: smaller amounts of amino sugars and an absence of 2-keto-3-deoxyoctonate; local Shwartzman reactivity and body weight-decreasing activity, even though the activities were rather weak compared with those of LPSs. Therefore, phenol-water extractive components of Mycoplasma salivarium might be of pathogenic importance in mediating damaging effects on the periodontium. PMID- 2264726 TI - Basic features of the staphylococcal heat shock response. AB - The major heat shock proteins of Staphylococcus aureus had apparent Mrs of 84,000, 76,000, and 60,000, and other prominent proteins of Mrs 66,000, 51,000, 43,000 and 24,000 were also induced. Staphylococcus epidermidis showed a similar response. These proteins were also induced by CdCl2, ethanol and apparently osmotic stress (1.71 M NaCl or 2.25 M sucrose). Most of the proteins sedimented with the membrane fraction, but the Mr 60,000 protein remained in the cytoplasm. PMID- 2264727 TI - Relationship between intestinal microecology and the translocation of intestinal bacteria. AB - It is now well known that endogenous bacteria can translocate from the intestinal tract and cause many of the complicating infections seen in severely ill, hospitalized patients. Of the hundreds of bacterial species in the intestinal tract, relatively few aerobic/facultative species appear to translocate with any frequency. Van der Waaij and colleagues (1971, 1972a, 1972b) originally proposed that, by a process termed 'colonization resistance', strictly anaerobic bacteria prevented the intestinal overgrowth and subsequent translocation of these potentially pathogenic aerobic/facultative bacteria. Selective antimicrobial decontamination, designed to maintain colonization resistance, has been effective in reducing the incidence of infectious morbidity in high risk patients. However, the mechanisms controlling bacterial translocation remain unclear, but appear to depend on host factors, as well as on factors inherent in the microbe itself. There is both clinical and experimental evidence supporting the concept that strictly anaerobic bacteria do not readily translocate. Bacteria that are able to survive within macrophages (e.g., Salmonella species and Listeria monocytogenes) translocate easier than others, and there is recent experimental evidence that normal intestinal bacteria may translocate to the draining mesenteric lymph node within host phagocytes. There is also evidence that anaerobic bacteria translocate along with facultative species in situations associated with intestinal epithelial damage, i.e., burn trauma, oral ricinoleic acid, and acute mesenteric ischemia. In contrast, recent experimental evidence demonstrates that facultative bacteria can translocate across a histologically intact intestinal epithelium, and that the ileal absorptive cell may be at least one portal of entry prior to transport into deeper tissues. It is anticipated that further clarification of the routes and mechanisms involved in bacterial translocation will provide new insights into the treatment and prevention of a significant proportion of the infectious morbidity seen in severely ill, hospitalized patients. PMID- 2264728 TI - Zygozyma smithiae sp.n. (Lipomycetaceae), a new ambrosia yeast from southern Africa. AB - A new species of the genus Zygozyma, Z. smithiae, was recovered from frass of the ambrosia beetle, Crossotarsus externedentatus in Northern Natal. A description of the new species and key to the genus are given. PMID- 2264729 TI - Ambulatory surgery. A study of patients' and helpers' experiences. PMID- 2264730 TI - Intraoperative music therapy. Effects on anxiety, blood pressure. PMID- 2264731 TI - Recommended practices. Positioning the surgical patient. AORN Recommended Practices Coordinating Committee. PMID- 2264732 TI - Recommended practices. Use of the pneumatic tourniquet. AORN Recommended Practices Coordinating Committee. PMID- 2264733 TI - Insulin use in the diabetic surgical patient. PMID- 2264734 TI - Liability for noncompliance with hospital policies, national standards. PMID- 2264735 TI - AIDS deaths rising in women. PMID- 2264736 TI - Ethical questions in organ transplantation still not answered. PMID- 2264737 TI - Research progressing on AIDS virus tests. PMID- 2264738 TI - If you are tired of working, you are not alone. PMID- 2264739 TI - Rinsing off glove powder. PMID- 2264740 TI - New ANA lobbyist pushes for nursing involvement in Washington. PMID- 2264741 TI - Grid implantation in seizure patients. A method to identify the epileptic focus. AB - Patients with epilepsy face many medical and social obstacles. The fortunate ones have their seizures controlled by medication, enabling them to have a normal life style. Others may benefit from grid implantation followed by excision of the seizure focus. PMID- 2264742 TI - Creutzfeldt-Jakob disease. A fatal neurodegenerative transmissible disorder. PMID- 2264743 TI - Inadvertent hypothermia. A comparison of postoperative cholecystectomy patients by age. PMID- 2264744 TI - A case cart system. Planning, implementing the system. PMID- 2264745 TI - [Pharmacological availability of erythromycin granules for children's use]. AB - Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied. With an account of the ++anatomo physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent. The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media. The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug. PMID- 2264746 TI - [Effect of dioxidine on extracellular proteins and enzymes in Staphylococcus aureus]. AB - Dioxidine++-induced changes were shown to occur in the protein composition of the cells of Staphylococcus aureus. The most significant damages were observed in the composition of exoproteins. Dioxidine++ had a specific inhibitory effect on intracellular nuclease, which was accompanied by a decrease in virulence and disorders in the toxin formation. PMID- 2264747 TI - [Comparative characteristics of lysozymes of different origin]. AB - Lysozymes with different molecular weights were isolated from homogenates of ticks or Ixodoidea with a procedure based on specific sorption of the enzyme by chitin. Lysozymes with a molecular weight of 13,800 were isolated from O. moubata, O. papillipes and A. lahorensis and lysozymes with a molecular weight of 15,000 were isolated from H. asiaticum and I. persulcatus. Micrococci and staphylococci proved to be the most sensitive to the lysozymes. E. coli and Salmonella spp. were less sensitive. The activity of the lysozymes from O. moubata, O. papillipes and A. lahorensis was 2 to 4 times as high as that of the yolk lysozyme and 4 to 8 times as high as that of the lysozymes from H. asiaticum and I. persulcatus. The activity of the yolk lysozyme was 2 or more times as high as that of the lysozymes from H. asiaticum and I. persulcatus. The lysozymes were resistant to heating in acid media. In alkaline media a marked loss of the activity was observed. PMID- 2264748 TI - [Natural penicillin resistance of Francisella tularensis]. AB - Altered viable forms of F. tularensis with spheroplast specific damages of the surface structures were isolated after the culture exposure to lithium chloride (0.5 and 1%). Study of natural penicillin resistance in the spheroplasts and bacterial forms of F. tularensis revealed their difference: the spheroplasts of the strains tested had a lower resistance to beta-lactam antibiotics than the bacterial forms while the activity of spheroplast beta-lactamase did not differ from that of the enzyme of the bacterial form and equalled 224 to 252 U/ml of the cell suspension. Therefore, on the model of the lithium-induced spheroplasts it appeared possible to show that the damages of the surface structures of the cell walls of F. tularensis changed the penicillin resistance level which was indicative of involvement of the F. tularensis cell walls in the phenomenon of the natural resistance to beta-lactams. PMID- 2264749 TI - [The meaning of the concept "ecological hazard"]. AB - Anthropogenic activity transforms the natural media and in the wide sense is a stimulus of further evolution. The late consequences of anthropogenic activity are mainly unpredictable. It is possible to acknowledge anthropogenic activity as ecologically hazardous only when it has a damaging effect on the health of man or interferes with its interests, i.e. while estimating it from egocentric positions. At present ecological hazards are first of all presented by industrial waste. PMID- 2264750 TI - [Synthesis and biological activity of aminophenylphosphonic derivatives of levorin]. AB - Reactions of levorin, a polyenic macrolide antibiotic, with aromatic aldehydes and hypophosphorous acid resulted in formation of its amino phenylphosphonium derivatives. Physicochemical and biological properties of the derivatives were studied. The levorin amino phenylphosphonium derivatives were shown to be low toxic and have antifungal and antiviral activities. PMID- 2264752 TI - [Rapid evaluation of the effectiveness of antibacterial drugs in experimental tularemia]. AB - Rapid estimation of the protective effect of antibacterial drugs on Fransiella tularensis for not more than 2 days was shown possible in experiments on albino mice infected with tularemia. High efficacy of aminoglycosides (kanamycin, gentamicin, streptomycin, amikacin, netilmicin, tobramycin, sagamycin, ribostamycin and sisomicin), tetracyclines (tetracycline, doxycycline, minocycline and methacycline), rifampicin, phosphomycin and oxolinic acid was determined with the recommended rapid method. Amoxycillin, ampicillin, piperacillin, carbenicillin, erythromycin, levomycetin, cefradine, cefmetazole, cefatrizine, cefoxitin, cefsulodin and bactrim (biseptol) proved to be inefficient against the tularemia causative agent. PMID- 2264751 TI - [Comparative study of the effectiveness of amikacin and streptomycin in experimental tularemia]. AB - In vitro study on antibacterial activity of amikacin in comparison to that of streptomycin revealed a high sensitivity of tularemia microbes of three geographical races to it. Amikacin showed a high therapeutic activity in treatment of albino mice infected with tularemia. The prospects of amikacin use in prophylaxis and treatment of tularemia are defined by its antibiotic activity against streptomycin-resistant forms of the tularemia causative agent. PMID- 2264753 TI - [Experimental and clinical study of nitazol as an antibacterial drug in the complex treatment of peritonitis]. AB - Antibacterial properties of the Soviet drug nitazol which is a derivative of imidazole were studied. It was shown that nitazol in a dose of 4-8 micrograms/ml was highly active against gram-negative nonsporulating anaerobes, gram-positive anaerobic cocci and spore-forming Clostridia spp. Unlike metronidazole, it was efficient against both standard and clinical strains of facultative anaerobes such as E. coli, S. aureus and Klebsiella spp. isolated from patients with peritonitis and being poly-resistant to antibiotics. It was found in vitro that the antibacterial effect of nitazol was higher when it was used in combination with some antibiotics. It was demonstrated on experimental models of peritonitis caused by Staphylococcus spp. and E. coli in mice that nitazol used alone or in combination with gentamicin had a favourable effect on the animal survival and lifespan. The combination of nitazol with gentamicin was applied in the combined treatment of appendicular peritonitis in 80 children and its high therapeutic efficacy was stated. Nitazol is useful as an antibacterial drug in the combined treatment of children with purulent peritonitis. PMID- 2264754 TI - [Ways of improving the effectiveness of bacteriological diagnosis and treatment of nonspecific lung diseases]. AB - Isolation, identification and drug sensitivity assay of microorganisms from pathological materials of 177 patients with nonspecific diseases of the lungs, mainly pneumonia, were performed on blood and selective "chocolate" agars by using Baktofok-MK, a new dry nutrient basis developed by the authors. Blood and "chocolate" agars based on the Hottinger's hydrolysate were used as the control media. It was shown that with the quantitative procedure for inoculating the pathological material, the experimental media based on Baktofok-MK were much more sensitive to growth properties that the control media. That made it possible to detect larger numbers of etiologically important microbial species on the blood agar and to isolate clinical strains of Hemophilus spp. from a larger number of specimens on the "chocolate" agar. PMID- 2264755 TI - [Cephalosporins in the treatment of urinary tract infections]. PMID- 2264756 TI - [Methodological approach to the study of the effect of antibiotics on the immune system]. PMID- 2264757 TI - [Errors in antibiotic therapy]. PMID- 2264758 TI - [Improving the qualifications of biotechnology specialists]. PMID- 2264760 TI - Probiotics in animal nutrition: a review. AB - The normal microflora colonizing the digestive tract in livestock species at five to six days after birth can be summarized as following: 400 to 500 different bacterial strains for a total count of 10(14) bacteriae. The role of the gut flora is multifarious: fermentation of feed compounds, induction of anatomical and physiological changes in the intestinal cell wall structure, increase in animal resistance against enteropathogenic bacteriae, etc. In the present review, the numerous hypotheses for explaining the beneficial effects of probiotics on zootechnical performances and also the healthy aspects for men and animals are summarized, and the possible mechanisms of bacterial attachment are enumerated. The different assumptions on mode of action and fixation mechanisms of probiotics in the gut are critically discussed, and the required characteristics of the ideal probiotic are listed. Finally, some zootechnical results obtained with lactic acid bacteria are shown for calves, piglets and broilers. PMID- 2264759 TI - [Cloning in Escherichia coli of a mitochondrial DNA fragment from Acremonium chrysogenum containing a region responsible for DNA replication]. AB - A bireplicone plasmid pSU901,4.6 kb in length, was constructed on the basis of plasmid pUC19 and the pstIB fragment, 1.9 kb in length, from mitochondrial DNA of A. chrysogenum. Based on the hybrid plasmid pSU901 and kanamycin resistance determinant, an autonomically replicating vector for A. chrysogenum, a culture producing cephalosporin C, is being constructed. PMID- 2264761 TI - [Determination of a prececal N-absorption from natural feed by 15N-labeled laboratory rats using the isotope dilution method]. AB - 60 Wistar rats (5 animals/group) received 12 different feedstuffs over a period of 7 days and were simultaneously labelled with 15N (orally by means of 15NH4Cl in the feed). In the subsequent 5 days faeces were collected in order to determine the apparent and true digestibility of crude protein. On the 13th experimental day the animals were killed 3 hours after the intake of half the daily ration and the atom-% 15N excess (15N') was determined in the TCA-soluble and TCA-precipitable fractions of the blood plasma and the digesta of the 2nd and 3rd thirds of the small intestine. Precaecal N-absorption was calculated with the help of the quotient [formula: see text] the blood plasma and the digesta The following values (in %) were registered in comparison to true N-digestibility (in the following in brackets): casein = 95.8 (99.2), whole egg = 92.1 (97.5), fish meal = 85.8 (93.4), dried skimmed milk = 98.4 (96.1), soybean meal = 79.6 (90.6), assay protein = 94.2 (98.9), wheat = 92.9 (90.7), barley = 84.3 (84.8), yeast, grown on molasses = 85.6 (87.2), yeast, grown on whey = 86.1 (88.5), biomass of liquid manure = 43.6 (68.9), activated sludge = 54.4 (64.1). One can conclude that the isotope dilution technique demonstrated here as an evaluation method is very well suited for the characterization of the N-digestibility of a feedstuff in the small intestine. PMID- 2264762 TI - [The effect of the protein level of feed on the energy maintenance requirement of rats during the course of growth and after the conclusion of the intensive growth phase using different feeding regimens]. AB - In two experiments with male Wistar rats energy metabolism was measured on the feeding level of maintenance in the course of growth and in various adult periods after the application of feed mixtures with various protein-carbohydrate quotas (10, 40 and 70% crude protein) according to two different feeding regimes. While there was a change of protein levels between the animal groups in periods 1 to 3 and 8 to 10 from one period to the other, the protein levels in periods 4 to 7 and 11 to 13 remained the same for each animal group. Irrespective of the feeding regime, a dependence of the energy maintenance requirement on the nutrients according to the expected values was measured, which result from the different efficiency of ATP synthesis in the oxidative degradation of the nutrients. On an average of the periods maintenance requirement amounted to 357 +/- 21, 399 +/- 16 and 443 +/- 28 kJ/kg LW0.75.d (experiment 1) and 350 +/- 29, 383 +/- 34 and 442 +/- 30 kJ/kg LW0.75.d (experiment 2) for 10, 40 and 70% crude protein in the feed. The relation between the maintenance requirement values was 100:112:124 and 100:109:126. This contrasts with the relative expected values of 100:108:115 and 100:109:116. PMID- 2264763 TI - [The ruminal nitrogen metabolism in calves and sheep. 1. Studies in calves]. AB - In a model experiment with calves supplied with duodenal re-entrant and rumen fistula resp. rations were tested that were energetically different (535 and 585 EFU cattle/kg DM) due to changing quotas of wheat starch and straw resp., dry matter intake being equal, and in which 45% of the crude protein came from soybean oil meal or urea resp. Due to the N-equivalent exchange of soybean oil meal by urea in rations for ruminating calves (130th day of life) the ammonia-N content in the rumen fluid, the quota of bacteria-N in the duodenal non-ammonia N (NAN) as well as the fermentation of crude plant protein in the ration were clearly increased. The iso-acid content in the rumen fluid and the utilization of the N available for bacteria N synthesis (N intake minus not degraded feed N in the duodenum) were reduced. An influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of duodenal NAN could not be proved. A ca. 20% higher energy intake by ruminating calves did not have a clear influence on other parameters, with the exception of the reduction of the molar quota of acetic acid in favour of the quota of propionic acid in the rumen fluid. PMID- 2264764 TI - Effect of feeding sheep on naturally spoiled rice straw, clover hay and concentrate feed mixtures. AB - The effects of feeding naturally contaminated feedstuffs to sheep were investigated through feeding of contaminated and uncontaminated clover hay, rice straw, and concentrate feed mixture were compared. The highest level of contamination with fungi was observed in the concentrate feed mixture followed by clover hay and rice straw. The most dominant mycotoxin in the contaminated feedstuffs was zearalenone. Contamination resulted in increases of crude protein, ash and silica in feedstuffs while both ether extract and crude fibre decreased. In vivo digestibility of different diet constituents in both contaminated and uncontaminated feedstuffs were determined using four mature Rahmani rams. Contamination resulted in significant increase in the digestibility of dry matter, crude fibre and energy. Contamination affected feed intake of the different feedstuffs particularly the concentrate feed mixture. A metabolism trial was also conducted to study the nitrogen and mineral balance. Retention of nitrogen and calcium was reduced when mouldy feeds were given. On the other hand, magnesium was relatively increased. Blood analysis for sheep at the end of the trials resulted in elevated values of inorganic phosphorus and phospholipid phosphorus and declined total nitrogen, calcium, cholesterol, calcium/phosphorus ratio and cholesterol/calcium ratio due to feeding on mouldy ration. Results of the urine analysis during the metabolism trials proved that mouldy ration increased the estimated values of the concentration of calcium, magnesium and vitamin C; whereas pH values, total nitrogen, ammonia nitrogen and inorganic phosphorus were declined during the feeding on the mouldy ration. Mouldy feeds tested, seemed to have toxic, nephritic and hepatic effect. PMID- 2264765 TI - [Infective endocarditis: analysis of 300 episodes]. AB - PURPOSE: Study of clinical features and etiologic agents, treatment and mortality of patients with infective endocarditis (IE). PATIENTS AND METHODS: 300 episodes of IE occurring in 288 patients, ages ranged between 0.2 and 78 (mean 30.76) years; 185 (62%) episodes occurred in males. RESULTS: a) etiologic agents: viridans group streptococci in 93 (31%) episodes, enterococci en 21 (7%), group D non enterococci in 19 (6%) (13 S. bovis), other streptococci in 14 (5%), Staphylococcus aureus in 59 (20%), Staphylococcus epidermidis in 14 (5%), gram negative bacteria in 16 (5%), gram-positive bacteria other than streptococci and staphylococci in 8 (3%), fungi in 4 (1%). The etiologic agents were not identified in 52 (17%) episodes; b) underlying cardiac diseases: valvular heart disease in 119 (40%) episodes, congenital heart disease in 37 (12%), prosthetic heart valves in 69 (23%), other heart diseases in 6 (2%). There was no evidence of previous heart disease in 69 (23%); c) treatment: surgical treatment was undertaken in 102 (34%) episodes. The frequency of surgical treatment in relation to the etiologic agents ranged between 1% (non-group D streptococci) and 62% (negative blood cultures). The frequency of operation in relation to underlying heart disease ranged between 17% (other heart diseases), 19% (congenital heart disease) and 54% (prosthetic heart valve); d) mortality: 78 (26%) patients died, 56 (28%) of the 198 submitted to medical treatment and 22 (21%) of the 102 submitted also to surgical treatment. The mortality in the different groups of etiologic agents ranged between 5% (non-group D streptococci) and 62% (gram positive bacteria other than streptococci and staphylococci); in relation to the underlying heart disease, the mortality was 16% in patients with other heart disease, 19% in valvular heart disease patients, 21% in patients with congenital heart disease, 23% in patients without known heart disease and 43% in patients with prosthetic heart valves. CONCLUSION: The mortality associated with IE remains still high in spite of modern treatment; the mortality is different in relation to the different etiologic agents and in relation to the cardiac status before the IE. PMID- 2264766 TI - [Clinical and angiographic characteristics of acute anteroseptal and upper lateral myocardial infarction: obliquous infarction; proposal of a new denomination for a specific type of infarction]. AB - PURPOSE: Analysis of clinical and angiographic characteristics of oblique (anteroseptal and high lateral) myocardial infarction. MATERIAL AND METHODS: Forty-two patients, 33 men, aged 30 to 79 years (mean 57) with oblique myocardial infarction were clinically evaluated and through coronary arteriography between ten day and eight months (mean of two months) of the acute event. RESULTS: Twenty patients had severe proximal lesions of left anterior descending artery (LAD), being single in thirteen. Four cases showed severe lesions in two arteries and three cases in three arteries. Fourteen patients exhibited collateral circulation to LAD or recanalization. Ejection fraction values were between 0.12 and 0.65 (mean 0.38). Eight patients died, four of them due to myocardial failure and four due to noncardiac causes. During follow-up angina pectoris was present in five, stroke in three and pulmonary embolism in two patients. CONCLUSION: Oblique myocardial infarction is associated with single and proximal lesion of LAD in the majority of the patients who underwent coronary arteriography, with low incidence of cardiac failure and death. PMID- 2264767 TI - [Endomyocardial biopsy and myocardial imaging with 67-gallium in the diagnosis of active myocarditis in children with dilated myocardiopathy]. AB - PURPOSE: This study was designed to compare 67Ga imaging and endomyocardial biopsy (EB) in children with severe dilated cardiomyopathy (DC), as well as to evaluate the results in a group of patients with active myocarditis submitted to immunosuppressive therapy. PATIENTS AND METHODS: Forty-four pediatric patients with severe DC were studied. Twenty males and 24 females from 10 months to 15 year old (median = 2.6 years). All patients were submitted to a protocol including 67Ga uptake and EB. In patients submitted to immunosuppressive therapy these procedures were repeated after six months. RESULTS: In 32 patients (72.7%) the EB revealed presence of inflammatory process; 21 (65.6%) of these had a positive 67Ga uptake and 11 (34.4%) negative. Twelve patients with no evidence of inflammatory process in the EB, nine (75%) presented negative 67Ga uptake. However, when the intensity of myocardial inflammatory was analysed (mild, moderate and severe) and correlated with 67Ga imaging, was observed that the majority of patients with negative 67Ga uptake (11 patients) had mild inflammatory infiltration (nine patients). In this way the 67Ga uptake demonstrated a good correlation in the diagnosis of moderate and severe inflammatory process in children with DC. This is important because the use of immunosuppressive drugs is indicated only in these group. CONCLUSION: The 67Ga imaging is a noninvasive diagnostic method with a good sensitivity to the diagnostic method with a good sensitivity to the diagnosis of AM in children with severe DC, demonstrating to be very useful in the therapeutic approach. PMID- 2264768 TI - [Late potentials in patients with myocardial infarction subjected to coronary thrombolysis]. AB - PURPOSE: Analyse the behavior of the late potentials (LP) in patients submitted to thrombolysis with success. MATERIAL AND METHODS: Thirty-five patients with acute myocardial infarction, 32 (91.4%) male with ages varying from 33 to 68 (mean 52.6). Thrombolysis was obtained during cinecoronarography with intravenous infusion "in bolus" of doses of 50 mg, 60 mg and 70 mg of rt-PA, with a new bolus of 30 mg at 60 minutes after the procedure. A new angiographic study was performed 12-48 hours late. The high resolution ECG was taken with the ART system model 1200 EPX, before, after and 72 hours later. The presence of electrical activity in the last 40 ms of the QRS complex with less than 20 mu volts in amplitude and more than 35 ms in duration characterized the LP. RESULTS: LP was observed in 16 (46%) patients during the phase of arterial occlusion. LP was recorded only in 23% after recanalization and in 26% when the infarcted related artery (IRA) remain opened. The reduction in the LP was 43.5%. Only one patient with LP had threatening arrhythmia. CONCLUSION: In patients with demonstrated thrombotic occlusion of the IRA, the recanalization diminished the incidence of LP in 43.5% of the patients. Further studies are necessary to achieve the exact clinical importance of these findings. PMID- 2264769 TI - [Lymphocytic and serum magnesium in older healthy and hypertensive subjects]. AB - PURPOSE: To study the lymphocyte and serum magnesium in older patients with and without arterial hypertension. PATIENTS AND METHODS: We studied the lymphocyte and serum Mg in 22 older patients, with diastolic blood pressure between 95 and 120 mmHg, not receiving drug treatment. A method of freezing produced total lysis of the cells. RESULTS: The mean lymphocyte Mg concentration in the older patients was 1.15 +/- 0.74 picomoles per 100 cells, significantly higher (p less than 0.05) than in the control group, that was 0.77 +/- 0.32 picomoles per 100 cells (lymphocyte Mg in older hypertensive patients/control = 1.49); there were no significant differences between groups with regard to serum Mg. Twelve older normotensive men studied also had lymphocyte Mg significantly higher than in the respective control group (lymphocyte Mg in older normotensive men/control = 1.70) and the serum Mg was also significantly higher than in the control group (1.63 +/ 0.12 versus 1.44 +/- 0.22 mEq/l. CONCLUSION: Since the high intracellular Mg concentration in the elderly patients may more accurately reflect the total body Mg status. We suggest to use Mg and Mg sparing diuretics in these patients, both hypertensive and normotensive, cautiously. PMID- 2264770 TI - [The mechanism of blood circulation: the truth in Harvey's work]. PMID- 2264771 TI - [Primary rhabdomyosarcoma of the heart in children. A case report]. AB - The authors report a case of a child, 10 years old with a primary rhabdomyosarcoma of the heart that obstructed both caval veins. The clinical picture that lasted just three months before the admission was characterized by persistent fever, accentuated loss of weight and a very deteriorated general aspect. We emphasize the clinical aspects and other subsidiary elements that easily allowed to make the precise diagnosis in life as well as the therapeutic measures and follow up, besides a review of the literature, where it was confirmed the rarity of this pathological entity. PMID- 2264772 TI - [Significance of intramural vascular injuries in myocardial revascularization. A case report]. AB - The authors report the case of 59 year-old hypertensive woman, suffering from angina pectoris, who died 24 hours after coronary by pass surgery due to cardiogenic shock. Autopsy revealed a small recent postero-lateral infarction. The venous by pass, however, were inconspicuous. Histologic examination showed extensive microarteriopathy with stenosing intimal fibro-elastosis and hyperplasia of the media, affecting 73% of the vessels with a diameter greater than 150 micra. The authors believe that the diffuse microangiopathy could have affected the myocardial reperfusion, and participated of the mechanical dysfunction. PMID- 2264773 TI - [Cardiogenic shock of uncertain etiology in a 58 years-old female patient]. PMID- 2264774 TI - [Use of laser in cardiovascular medicine]. PMID- 2264775 TI - [Pathogenic and immunological aspects of infective endocarditis]. PMID- 2264776 TI - Coronary balloon angioplasty and vascular response to injury. Perspectives for the 1990's. PMID- 2264777 TI - [Infective endocarditis: a Brazilian experience]. PMID- 2264778 TI - [Obliquous myocardial infarction: a new concept?]. PMID- 2264779 TI - [Prevalence of arterial hypertension]. PMID- 2264780 TI - [Epilepsy at a psychiatric hospital]. AB - Epilepsy was surveyed in the largest psychiatric hospital in the Santa Catarina State, southern Brazil. This establishment was designed for one thousand long term beds but at the time of the survey there were 1126 inpatients. Diagnosis ranged from anxiety neurosis to schizophrenia although patients with epilepsy, with or without psychiatric symptoms were also admitted. The following aspects were analyzed: prevalence of epilepsy, seizure types, antiepileptic drug treatment and psychiatric diagnosis. 171 patients with epilepsy were identified (prevalence 152/1000), generalized tonic clonic attacks were the commonest seizure type and polytherapy was the standard treatment. In at least 85 of the epileptic patients there was no reason for prolonged institutionalization in a psychiatric environment. Moreover, most of the sample were prescribed large amounts of sedative drugs. A multidisciplinary approach and outpatients services are urgently required to improve the prognosis and well-being of patients with epilepsy who are referred to psychiatric care. PMID- 2264781 TI - [Diagnosis and treatment of myasthenia gravis: study of an inpatient population]. AB - Between 1974 and 1987 we have examined 50 patients with the diagnosis of myasthenia gravis. Female preponderance (2.5: 1) was found. Also, it was observed that most of the patients were aged between 20 and 49 years. Beside the clinical examination, the following tests were performed: (1) edrofonium test, (2) supramaximal repetitive nerve stimulation, (3) serum acetylcholine antibodies titers and (4) intraperitoneal passive transference of patient's sera to mice and recording of meepp's amplitude in the phrenic-diaphragm preparation in vitro. These four tests gave positive values for myasthenia in 90 to 100% of the cases. Thymus radiological examination was carried out by pneumomediastinography, which proved to correlate with the histological picture of the gland, and computed tomography, which disclosed some discrepances with the histology. Treatment was based on anticholinesterase drugs, corticosteroids and thymectomy, being the corticosteroids the most valuable therapeutical tool. Nine patients treated with steroids disclosed transitory worsening of their signs and symptoms at very early stages after onset of corticosteroid therapy, 6 of them had a disfavorable course in their follow-up. This observation seem to have value in the early prognosis of the disease. PMID- 2264782 TI - Brain tumours in south Brazil: a retrospective study of 438 cases. AB - All brain tumours diagnosed since 1967 in a University Hospital in the Southern region of Brazil were reviewed and clinical information concerning age, sex, symptoms and evolution were analysed. 88.1% of tumours were primary neoplasms and the rest secondary deposits. There was a male predominance and the second and fifth decades of life were the most affected. The main presenting symptoms were headache, vomiting, hemiparesis, loss of vision and epilepsy. The commonest tumour was of astrocytic origin (36.3%) amongst which the malignant ones, including glioblastoma multiforme, predominated. These tumours were frequent in the cerebral hemispheres (31.3%), particularly in the frontal lobes. The time of evolution from the beginning of the clinical manifestations until the first hospital admission was also studied. The authors discuss the clinical and pathological observations in relation to other large series analysed in the literature. PMID- 2264783 TI - Clinical, radiological and cerebrospinal fluid presentation of neurocysticercosis: a prospective study. AB - The wide clinical spectrum of neurocysticercosis has led to many attempts at clinical, radiological, CSF and other classifications. Based on an objective review of the relevant literature and on a prospective study of 42 patients with active neurocysticercosis, a new classification is proposed, based on clinical, tomographic, magnetic resonance and CSF evidence of viability of cysts. The first step is to define whether the disease is active or not. Inactive disease may be parenchymal calcifications or hydrocephalus. Active disease may be intraparenchymal, extraparenchymal or mixed. Statistical analysis of 42 cases with active disease shows intraparenchymal disease to occur in younger patients, perhaps more frequently in females, and to have a better prognosis than extraparenchymal of mixed disease. The latter appears to have the worst prognosis. Therapeutic implications are that only active disease warrants etiological therapy. There remain doubts about the best therapy for some infrequent subtypes of extraparenchymal and mixed disease. PMID- 2264784 TI - [Social aspects of premature mortality (15 to 59 years old) caused by cerebrovascular diseases]. AB - The loss of productive years for premature death (15-59 years) due to cerebrovascular diseases (CVD) was estimated on the basis of official mortality statistics for Brasil, 1985. Estimations were made for the 5 macro-regions of the country--North, Northeast, Southeast, South and Midwest, as well as for selected capital cities located in each of the regions, respectively: Belem, Salvador, Sao Paulo, Porto Alegre and Brasilia. Men lost 158,194 years of productive life while the loss for women was 128,905 years. The average of years lost/person varied between 11.5 (South) and 13.4 (Midwest) for males and between 12.9 (North) and 14.1 (Midwest) for females. The proportions of productive years lost were greater for women in all five regions. In the capital cities, the average loss of years were similar to the respective macro-regions, although for Salvador there was an increase for both genders as compared to the Northeast. The social costs of such premature deaths is then discussed, estimating a potential reduction of 200,000 years from the total losses, in case of treatment and control of high blood pressure in the Brazilian population. PMID- 2264785 TI - Photoparoxysmal responses. AB - Sixty-five outpatients with photoparoxysmal response (PPR) during routine EEG were studied. The PPR showed prevalence in women (75.4%). Seizures were found in 66.1% of cases. The rest recordings were abnormal in 41.8% with prevalence of generalized paroxysm. Eight patterns of PPR were observed, being polyspike mixed to slow wave the most frequent (53%). The epileptic group showed a bimodal distribution in the several bands of photic stimulation, near 8 and 20-24 Hz. A sustained paroxysmal abnormality persisting after the photic stimulation was present in 6 epileptic patients. PMID- 2264786 TI - Craniocerebral involvement in lymphoma. AB - Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3%) had lymphomatous craniocerebral infiltration. The principal factors of risk for this complication were: advanced stage of the lymphoma (III or IV), diffuse histiocytic, diffuse poorly differentiated lymphocytic, or mixed cellularity lymphoma histological type, bone marrow involvement, and previous systemic chemotherapy. Thirty-two per cent of the cases of meningeal lymphomatous infiltration were asymptomatic and represented autopsy findings. CT-scan was an useful test to detect brain focal parenchymatous infiltration, as opposed to meningeal infiltration. Mean survival time in patients with lymphomatous meningeal infiltration was 4.3 months, following the combined use of systemic chemotherapy, radiation therapy and intrathecal methotrexate. Two cases had primary cerebral lymphoma, although without associated immunodeficiency. Twenty patients (2%) had intracranial hemorrhage, in clear relationship with platelet alterations. Fifteen patients (1.5%) had CNS infection, caused by common bacteria or opportunistic agents. In 7 cases, the diagnosis was made at autopsy. Thirty six autopsies were performed. In 8 cases (22%), pathologic findings such as, demyelination, microcalcifications, coagulative necrosis, or gliosis, suggested complications from treatment. PMID- 2264787 TI - [Neurophysiological evaluation using multimodal sensory evoked potentials in patients in coma: general aspects]. AB - Noninvasive sensory evoked potentials (SEP) performed at bedside in the Intensive Care Unit for patients in coma can be helpful in establishing both a diagnosis and a prognosis. Based on a more than 6-year experience on this subject, the authors discuss general aspects concerning these EP, their probable known generators, and propose a classification depicting different aspects observed for flash visual EP (F-VEP), brainstem auditory EP (BAEP), and median nerve somato sensory EP (SSEP). Isolated, SSEP shows the best diagnostic and prognostic performance. Nevertheless, the authors consider that multimodality SEP are even better than any isolated EP study; cross-correlating information generated through a horizontal (F-VEP), a vertical (SSEP), and a pathway focusing brainstem in greater detail (BAEP) allows the neurophysiological establishment of the level of lesion in the CNS from a better perspective; besides, SEP can help setting the diagnosis of brain (encephalic) death, and the diagnosis of particular problems concerning each pathway. Notwithstanding, most important is prognosis definition, and the findings are summarized. Abnormal BAEP implies bad prognosis, as would be expected considering the severity of a brainstem lesion; on the other hand, a normal BAEP per se does not allow a precise definition, resting on other EP the role prognosis characterization. SSEP if bilaterally normal or only mildly abnormal imply good prognosis; bilateral absence of SSEP thalamo-cortical components has always carried a bad prognosis, since younger patients may at best evolve into a persistent vegetative state; SSEP intermediary results are more often accompanied by variable evolution. FVEP results parallel those of SSEP. PMID- 2264788 TI - [Antigenic expression in human choroid plexus carcinoma: report of 2 cases]. AB - Primary neoplasms of choroid plexus are rare. Six morphological variants have been described: papillary, cystic, acinar, mucus-secreting, oncocytic, and anaplastic. The anaplastic variant, the so-called choroid plexus carcinoma, is the rarest of all and can metastasize. The differential diagnosis of the anaplastic variant of choroid plexus neoplasms with adenocarcinomas, melanomas and undifferentiated neoplasms can be troublesome chiefly in adults. The now large use of immunocytochemical techniques in tissue section has become a powerful tool in the analysis of cell lineages, tumoral and non-tumoral. Nevertheless, the choroid plexus neoplasms have shown a complex and a somewhat confusing pattern of antigenic expression. In two choroid plexus carcinomas (one localized in the right lateral ventricle from a boy of 1 year and 9 months old, and the other localized in the left lateral ventricle from a girl of 3 years old) the following antigens were searched (using the avidin-biotin-peroxidase complex): glial fibrillary acidic protein (GFAP) with monoclonal and polyclonal antibodies; cytokeratins of 40-50kDa, cytokeratins of 60-70kDA (callus cytokeratin), neuronal specific enolase (NSE) and S-100 protein with monoclonal antibodies. The two neoplasms showed immunoreactivity against NSE, S-100 protein and cytokeratin of 40-50kDA. The neoplasm of the boy exhibited glial differentiation having immunoreactivity against GFAP with monoclonal and polyclonal antibodies. PMID- 2264789 TI - [Lhermitte's sign during lateral cervical puncture: survey of possible accidents in the lateral C1-C2 puncture and report of 2 cases of spinal cord penetration]. AB - Lhermitte's sign was referred by two patients during lateral cervical puncture (LCP) due to accidental puncture of the spinal cord; no sequelae were observed in these patients. A brief review of the literature is presented, concerning: 1. Lhermitte's sign; 2. reported accidents during LCP. Avoidance of neural and/or vascular injuries is possible by employing the posterior approach to LCP (puncture of the dorsal spinal subarachnoid space at C1-C2). The lateral suboccipital puncture (at the atlanto-occipital space) of the cisterna magna is also recommended. PMID- 2264790 TI - [Photosensitive epilepsy: report of 2 cases]. AB - Reports on photosensitive epilepsy are uncommon. The authors review the literature, and special attention is given to television epilepsy. Two cases are reported and discussed. PMID- 2264791 TI - [Primary reading epilepsy: therapeutic efficacy of clonazepam in one case]. AB - Primary reading epilepsy is a rare form of reflex epilepsy, in which reading is the specific stimulus evoking attacks. The authors report a case of an 18-year old man who since the age of 17 presented myoclonic jaw jerking provoked exclusively by reading. In one episode, in which reading was not interrupted, jerks were followed by a generalized convulsive seizure. EEG with routine activating procedures was normal, while EEG recorded during reading showed bilaterally synchronous paroxysmal small-voltage spikes, more prominent in frontocentral regions, coinciding with jaw myoclonus. Complete clinical seizures control and EEG normalization were achieved with clonazepam 2 mg daily in a 24 month follow-up. PMID- 2264792 TI - [Pure spinal leptomeningeal cysticercosis]. AB - An adult female patient presented with an exclusively spinal leptomeningeal infestation by cysticercosis (restricted to the cauda equina), verified in surgery. The role of the vertebral vein system in the spread of cysticercosis larvae is discussed. A commentary on the possibility that cysticercosis of the basal cisterns may be due to ascending migration of primarily spinal cysticerel, as originally proposed by Isamat de la Riva, is stated. PMID- 2264793 TI - [Syringomyelia: review of the literature and report of a case]. AB - A thorough review of history, pathophysiology, clinical manifestations, diagnosis and treatment of syringomyelia is presented by the authors, followed by a case report in which the diagnosis was confirmed by magnetic resonance imaging. PMID- 2264794 TI - [Interhemispheric disconnection syndrome following total callosotomy associated to anterior commissurotomy for the treatment of intractable epilepsy: a case report]. AB - The authors provide a brief review of the indication criteria of callosotomy for the treatment of medically intractable seizures. They report a surgical case with the classical picture of disconnection (split brain) syndrome, following a two staged complete callosotomy plus anterior commissurotomy. The disconnection syndrome was more severe on the first 5 days post-operatively, improving quickly after the 11th day; there was almost complete functional recovery and a great reduction in seizure frequency. PMID- 2264795 TI - Effects of trauma to the mandibular nerve on human perioral directional sensitivity. AB - The capacity of 4 patients who had previously experienced trauma to their mandibular nerves to distinguish opposing directions of tactile motion over the distribution of the mental nerve was compared to that of 8 neurologically normal adults. Brushing stimuli were delivered to the perioral region and were precisely controlled for their velocity, the length of skin traversed, the width of skin contacted, and the orientation and direction of motion. A temporal, 2 alternative, forced choice method was used to obtain estimates of directional sensitivity, d'. It was discovered that impairment in cutaneous directional sensitivity could be readily detected within areas of hypaesthesia. Although directional sensitivity was found to increase linearly with the length of skin traversed for both the patients and the neurologically normal adults, the slope and the x-intercept of the linear relationship differed between the two groups. The difference in the slope suggests that direction discrimination within the hypaesthetic areas is relatively insensitive to changes in the length of skin traversed. The difference in the x-intercept suggests that a greater length of skin must be traversed before any information about direction is made available at the hypaesthetic sites. The dependency of the capacity of neurologically normal and impaired individuals to process information about direction of tactile motion on the length of skin traversed and the velocity of stimulation suggests that a high degree of stimulus control is required for the detection and quantification of subtle neurosensory deficits. PMID- 2264796 TI - Alkali-soluble and insoluble fluoride in erupted and unerupted sound enamel of human third molars in vivo. AB - The amounts of firmly and loosely bound fluoride were determined in sound enamel of unerupted and erupted teeth which had been exposed in vivo for 1-16 yr to brushing at least once a day, and occasionally to mouth rinsing and the application of sealers. Enamel was sampled by an acid-etch procedure, and the fluoride levels were measured with an adapted fluoride ion-selective electrode. Unerupted enamel was etched significantly (p less than 0.05) deeper than erupted enamel up to a depth of at least 8 microns. Significant differences (p less than 0.05) were found between the mean enamel fluoride concentrations of unwashed and alkali-washed, erupted teeth up to a depth of at least 3 microns and also between unwashed or washed, erupted versus unwashed or washed, unerupted teeth. At a depth of 3 microns, the fluoride treatments of enamel had increased the total amount of fluoride by approx. 78% of which approx. 53% was loosely bound fluoride (like CaF2) and 47% firmly bound (like fluorapatite). No increase in sound enamel fluoride as a result of topical treatments over a period of up to 16 yr could be found at a level deeper than 20 microns. PMID- 2264797 TI - The effect of cyclophosphamide on the eruption of impeded and resected incisors in rats. AB - It is known that a single dose of cyclophosphamide (40 mg.kg-1 intraperitoneal) slows the eruption of unimpeded incisors but has no effect on impeded incisors. In this study incisors that were impeded when cyclophosphamide was given were subsequently made unimpeded. When they were unimpeded they erupted more slowly than the controls. Therefore the changes cyclophosphamide produces which slow eruption are formed in impeded incisors but have an effect only in unimpeded incisors. It has been reported that cyclophosphamide slows the eruption of resected incisors when it is given before the resection. In a second experiment cyclophosphamide was given after the resection and had no effect on eruption rates. It is suggested from these and earlier findings that cyclophosphamide slows eruption by imposing a maximum on the rate at which it can occur and that it does so through the changes it produces in the periodontal ligament. The periodontal changes make it harder for the tooth to move rather than altering the forces moving the tooth. This explanation of how cyclophosphamide slow eruption produces an alternative interpretation of some, but not all, of the findings that have been cited as evidence that there are two mechanisms of tooth eruption. PMID- 2264798 TI - Morphological and biochemical evidence for elastic fibres in the Syrian hamster temporomandibular joint disc. AB - Elastic fibres are considered to be important for the normal biomechanical functions of the TMJ. The objective here was to correlate morphological evidence for the presence of elastic fibres in discal tissues with biochemical evidence for elastin. For light microscopy, the joints were removed en bloc, processed for paraffin embedding, sectioned and stained with resorcin-fuchsin. For biochemical study, a radioimmunoassay for desmosine was used to estimate the amount of elastin in excised articular discs. The histological preparations showed that numerous elastic fibres were present in various areas of the disc and in some of the discal attachments to surrounding bone. Radioimmunoassay also indicated that elastin was present in these tissues. Therefore, the biochemical findings support the morphological in suggesting that elastic fibres are present in the articular disc of the hamster TMJ. PMID- 2264799 TI - Identification of epidermal growth factor receptor in human buccal mucosa. AB - EGF receptor was identified and its binding characteristics were determined. Buccal mucosa was obtained from 12 healthy volunteers (6 males and 6 females) and assayed individually for [125I]-EGF binding. The specific binding of [125I]-EGF to the receptor ranged from 2.85 to 6.12 fmol/mg protein. There was no significant difference in binding between male and female (4.31 +/- 0.61 versus 3.94 +/- 0.53 fmol/mg protein; mean +/- SEM). Individual tissue homogenates were pooled for Scatchard analysis and cross-linking experiments. Scatchard analysis produced curvilinear plots with a Kd of 0.71 nM and Bmax of 0.024 pmol/mg protein for the high-affinity binding sites, and Kd of 435 nM and Bmax of 9.92 pmol/mg protein for the low-affinity binding sites. To determine the molecular weight of the EGF receptor, the [125I]-EGF and receptor complex were cross-linked by DSS and subjected to SDS-PAGE. The autoradiogram of the gel revealed one major protein band of 160K and a minor band of 170 K, characteristics shared with the EGF receptors in other tissues. The study is thought to be the first to demonstrate the presence of the EGF receptor in human buccal tissue and to show its biochemical features. PMID- 2264800 TI - Call for reports of small animal poisoning by new rat killer. PMID- 2264801 TI - Effects of suckling on oestradiol benzoate induced LH release in post-partum, ovariectomised cows. AB - Twelve suckling and 12 non-lactating post-partum cows were treated with a progesterone-releasing pessary for 7 or 14 d followed by an injection of 500 micrograms oestradiol benzoate (ODB) 24 h after pessary removal or no injection. Suckling had no significant effect on plasma progesterone concentrations (plasma P4) or plasma luteinising hormone concentrations (plasma LH) during pessary insertion. After pessary removal plasma LH rose in response to ODB. The extent of the rise was similar in suckling and non-lactating cows treated with progesterone for 14 d but was significantly lower in non-lactating than suckling cows (P less than 0.025) treated for 7 d. These findings indicate that suckling increases the responsiveness of plasma LH in post-partum cows following progesterone and oestrogen treatment compared to non-lactating cows and that extended treatment with progesterone can remove this difference. PMID- 2264802 TI - The reversal of xylazine/ketamine immobilisation of fallow deer with yohimbine. AB - Fallow deer were immobilised using a combination of xylazine and ketamine. Adult males (n = 10) and adult females (n = 10) received 4 mg/kg of each drug intramuscularly. Juveniles (n = 11) received 2 mg/kg of each drug, intravenously. Times to recumbency were as follows: adult males 4.9 +/- 2.9 min, adult females 4.1 +/- 1.9 min, juveniles 2.3 +/- 1.1 min. After 30 min each deer received 0.2 mg/kg of yohimbine, or an equal volume of sterile diluent intravenously. Yohimbine substantially reduced the recovery times of treated deer. Adults males were releasable 7.2 +/- 4.3 min after yohimbine administration, whereas control males were not releasable until 165 +/- 18 min. Treated adult females were releasable after 6.6 +/- 4.3 min, while control females were not releasable until 84 +/- 29 min. Juveniles were releasable 2.1 +/- 0.8 min after administration of yohimbine but control juveniles were not releasable until 62 +/- 16 min. Xylazine/ketamine administration produced statistically significant changes in packed cell volume, total plasma protein, albumin, sodium, glucose, creatine phosphokinase and inorganic phosphate values after 30 min. Yohimbine administration had no effect on these changes. PMID- 2264803 TI - Chronic hypertrophic pyloric gastropathy in 14 dogs. AB - Ten male and 4 female dogs with chronic hypertrophic pyloric gastropathy were seen at the Sydney Veterinary Teaching Hospital in the period 1982-88. The most commonly affected breeds were the Shihtzu and Maltese. The mean age was 8.2 yr and the mean body weight 6.5 kg. The most common clinical signs were vomiting, weight loss, polydipsia and depression. Hypokalaemia was present in 11 of 12 dogs examined and hypochloraemia in 10 of 11 dogs examined. Five of the six dogs that had blood gases measured were found to have a metabolic alkalosis. Surgery was performed on 13 dogs; pyloromyotomy 7, pyloroplasty 4, gastroduodenostomy 2. There was a recurrence of symptoms in one pyloromyotomy dog, and fatal ulceration and perforation of the cardia occurred in one pyloroplasty case. The remaining 11 dogs had a mean known symptom-free survival time of 20 mo. This study confirms the preponderance of affected males, identifies electrolyte and blood gas disturbances as significant complication of chronic hypertrophic pyloric gastropathy, and suggests that relatively minor surgery (pyloromyotomy) may have a place in the treatment of a selected subgroup of cases. PMID- 2264804 TI - Diseases of young captive crocodiles in Papua New Guinea. AB - To identify causes of mortality in young captive crocodiles, detailed necropsy and laboratory examination was done on 54 (30 Crocodylus porosus, 22 C. novaeguineae, 2 of unrecorded species). Although multiple infections often confounded interpretation it was concluded that the major infectious diseases, of approximately equal importance, were coccidiosis, bacterial septicaemia with Gram negative organisms, and metazoan parasitism including ascariasis and pentastomiasis. A range of other lesions and agents was recognised, including keratitis, enteritis of unknown aetiology, non-suppurative encephalitis, traumatic peritonitis and trematodes located in renal tubules, gut and blood vessels. Some crocodiles in poor condition had only mild lesions associated with metazoan parasites and the cause of death or illness could not be clearly determined, although it was considered likely that adaptation failure was a contributing factor. PMID- 2264805 TI - A phalangeal fusion defect and osteochondrosis dissecans with subluxation of the distal interphalangeal joints in a foal. AB - A fusion defect of the proximal and middle phalanges of both hindlimbs, osteochondrosis dissecans of the distal interphalangeal joints of the forelimbs, and subluxation of all 4 distal interphalangeal joints occurred in a Standardbred filly. Lameness was the first abnormality noted and was observed at one week of age in the left forelimb and progressed until all 4 limbs were affected by 5 weeks of age. On radiographs of both forelimbs, the distal interphalangeal joints were subluxated with irregularity and lucency of subchondral bone. On radiographs of the distal hindlimbs, there was a subluxation of both distal interphalangeal joints and loss of the proximal interphalangeal joint spaces with fusion of the proximal and middle phalanges. The foal was euthanised. On necropsy, there were focal areas of erosion of articular cartilage in the distal interphalangeal joint of both forelimbs. The proximal and middle phalanges of both hindlimbs were fused. Histopathological examination of the distal interphalangeal joint of the right foreleg showed loss of articular cartilage and degenerative changes in the exposed subchondral bone. PMID- 2264806 TI - Chlamydiosis in commercial ducks. PMID- 2264807 TI - Vasoformative proliferations in a rufous bettong. PMID- 2264808 TI - The isolation and identification of Edwardsiella tarda from a diseased native Australian eel (Anguilla reinhardtii). PMID- 2264809 TI - In vitro and in vivo studies on the effects of flystrike dressings on larvae of Lucilia cuprina. PMID- 2264810 TI - An investigation of all north Queensland commercial poultry flocks for evidence of infection with Newcastle disease virus. PMID- 2264811 TI - Efficacy of closantel against infestations of screw-worm fly Chrysomya bezziana. PMID- 2264812 TI - Carbohydrate malabsorption in dogs assessed using bioluminescence assays to measure simple sugars. PMID- 2264813 TI - Serosal proliferations in koalas. PMID- 2264814 TI - Suspected Cryptostegia grandiflora (rubber vine) poisoning in horses. PMID- 2264815 TI - Dual modulation of chloride conductance by nucleotides in pancreatic and parotid zymogen granules. AB - The regulation of Cl- conductance by cytoplasmic nucleotides was investigated in pancreatic and parotid zymogen granules. Cl- conductance was assayed by measuring the rate of cation-ionophore-induced osmotic lysis of granules suspended in iso osmotic salt solutions. Both inhibition and stimulation were observed, depending on the type and concentration of nucleotide. Under optimal conditions, the average inhibition measured in different preparations was 1.6-fold, whereas the average stimulation was 4.4-fold. ATP was inhibitory at 1-10 microM but stimulated Cl- conductance above 50 microM. Stimulation by ATP was more pronounced in granules with low endogenous Cl- conductance. The potency of nucleotides in terms of inhibition was ATP greater than adenosine 5'-[gamma thio]triphosphate (ATP[S]) greater than UTP much greater than or equal to CTP much greater than or equal to GTP much greater than or equal to guanosine 5' [gamma-thio]triphosphate (GTP[S]) much greater than or equal to ITP. The potency with respect to stimulation had the following order: adenosine 5'-[beta gamma methylene]triphosphate (App[CH2]p) greater than ATP greater than guanosine 5' [beta-thio]diphosphate (GDP[S]). Adenosine 5'-[beta gamma-imido]triphosphate (App[NH]p) was also stimulatory, and was more potent than ATP in the parotid granules, but less potent in the pancreatic granules. Aluminium fluoride stimulated Cl- conductance maximally at 15-30 microM-Al3+ and 10-15 mM-F. F was less effective at higher concentrations. Protein phosphorylation by kinases was apparently not involved, since the nucleotide effects (1) could be mimicked by non-hydrolysable analogues of ATP and GTP, (2) showed reversibility, and (3) were not abolished by the protein kinase inhibitors 1-(5-isoquinolinesulphonyl)-2 methylpiperazine (H-7) or staurosporine. The data suggest the presence of at least two binding sites for nucleotides, whereby occupancy of one induces inhibition and occupancy of the other induces stimulation. PMID- 2264816 TI - Glucose utilization and disposal in cardiothoracic and skeletal muscles during the starved-to-fed transition in the rat. AB - Glucose utilization indices (GUI) increased to fed values in diaphragm and oxidative skeletal muscles and exceeded fed values in non-oxidative muscles within 2 h of re-feeding chow to 48 h-starved rats. Cardiac GUI reached fed values only after 7 h. Glycogen deposition accounted for most of the glucose phosphorylated in skeletal muscle over the first 2 h in oxidative muscles and over the first 4 h in non-oxidative muscles. In oxidative muscles, the contribution of glycogen deposition to total glucose 6-phosphate disposal diminished as re-feeding was extended from 2 to 6 h. PMID- 2264818 TI - Purification and characterization of an iron-induced ferritin from soybean (Glycine max) cell suspensions. AB - Ferric citrate induces ferritin synthesis and accumulation in soybean (Glycine max) cell suspension cultures [Proudhon, Briat & Lescure (1989) Plant Physiol. 90, 586-590]. This iron-induced ferritin has been purified from cells grown for 72 h in the presence of either 100 microM- or 500 microM-ferric citrate. It has a molecular mass of about 600 kDa and is built up from a 28 kDa subunit which is recognized by antibodies raised against pea (Pisum sativum) seed ferritin and it has the same N-terminal sequence as this latter, except for residue number 3, which is alanine in pea seed ferritin instead of valine in iron-induced soybean cell ferritin. It contains an average of 1800 atoms of iron per molecule whatever the ferric citrate concentration used to induce its synthesis. It is shown that the presence of 100 microM- or 500 microM-ferric citrate in the culture medium leads respectively to an 11- and 28-fold increase in the total intracellular iron concentration and to a 30- and 60-fold increase in the ferritin concentration. However, the percentage of iron stored in the mineral core of ferritin remains constant whatever the ferric citrate concentration used and represents only 5-6% of cellular iron. PMID- 2264817 TI - Determination of the critical concentration required for desmin assembly. AB - The critical concentration required for filament assembly in vitro from highly purified desmin was determined by both turbidity and centrifugation assays. Assembly was done in the presence of 2 mM-Ca2+, 2 mM-Mg2+ or 150 mM-Na+ at 2, 22 and 37 degrees C. Similar values for critical concentration were obtained by both assays. As temperature increased, critical concentration decreased for each cation. The critical concentration was lowest in the presence of Ca2+ at 2, 22 and 37 degrees C, but was highest in the presence of 150 mM-Na+ at 2 degrees C. Negative staining showed that supernatants from the centrifugation assays contained protofilaments, protofibrils and short particles (less than 300 nm), but pellets contained long filaments (greater than 1 micron) with an average diameter of 10 nm. As the temperature increased, both the average diameter and average length of particles in the supernatant increased. Thermodynamic analysis indicated that hydrophobic interactions were dominant during desmin assembly, but that ionic interactions might also be involved. Our results demonstrated that the specific cation and temperature and temperature-cation interactions all are important in assembly of desmin intermediate filaments. PMID- 2264819 TI - Evaluation of steady-state kinetic parameters for enzymes solubilized in water-in oil microemulsion systems. AB - 1. Equations are derived for the steady-state kinetics of substrate conversion by enzymes confined within the water-droplets of water-in-oil microemulsion systems. 2. Water-soluble substrates initially confined within droplets that do not contain enzyme are assumed to be converted into product only after they enter enzyme-containing droplets via the inter-droplet exchange process. 3. Hyperbolic (Michaelis-Menten) kinetics are predicted when the substrate concentration is varied in microemulsions of fixed composition. Both kcat. and Km are predicted to be dependent on the size and concentration of the water-droplets in the microemulsion. 4. The predicted behaviour is shown to be supported by published experimental data. A physical interpretation of the form of the rate equation is presented. 5. The rate equation for an oil-soluble substrate was derived assuming a pseudo-two-phase (oil & water) model for the microemulsion. Both kcat. and Km are shown to be independent of phi aq. Km is larger than the aqueous solution value by a factor approximately equal to the oil/water partition coefficient of the substrate. The validity of the rate equation is confirmed by published data. PMID- 2264821 TI - The specificity of the IgA receptor purified from human neutrophils. AB - A receptor for IgA was purified from human polymorphonuclear neutrophils (PMN) by affinity chromatography on human serum IgA-Sepharose. The receptor appeared on SDS/polyacrylamide gels as a diffuse band with an apparent molecular mass of 50 70 kDa, whether reduced or non-reduced. During purification, the protein showed remarkable stability to proteolytic digestion by endogenous PMN proteinases. Purified radioiodinated receptor re-bound to IgA-Sepharose, but not to IgG Sepharose or BSA-Sepharose. The binding of the receptor to IgA-Sepharose was inhibited in a dose-dependent manner by human serum IgA1 or IgA2 or secretory IgA1 or IgA2, but not by IgG or IgM. Binding of receptor to IgA-Sepharose was also inhibited by the Fc fragment of IgA, but not by the Fab fragment. An IgA fragment produced by digestion with pepsin which lacks the CH3 domain also inhibited binding, but to a more limited extent than did the whole IgA molecule. PMID- 2264820 TI - Localization of the forskolin photolabelling site within the monosaccharide transporter of human erythrocytes. AB - Chemical and proteolytic digestion of intact erythrocyte glucose transporter as well as purified transporter protein has been used to localize the derivatization site for the photoaffinity agent 3-[125I]iodo-4-azido-phenethylamino-7-O succinyldeacetylforskol in [( 125I]IAPS-forskolin). Comparison of the partial amino acid sequence of the labelled 18 kDa tryptic fragment with the known amino acid sequence for the HepG2 glucose transporter confirmed that the binding site for IAPS-forskolin is between the amino acid residues Glu254 and Tyr456. Digestion of intact glucose transporter with Pronase suggests that this site is within the membrane bilayer. Digestion of labelled transporter with CNBr generated a major radiolabelled fragment of Mr approximately 5800 putatively identified as residues 365-420. Isoelectric focusing of Staphylococcus aureus V8 proteinase-treated purified labelled tryptic fragment identified two peptides which likely correspond to amino acid residues 360-380 and 381-393. The common region for these radiolabelled peptides is the tenth putative transmembrane helix of the erythrocyte glucose transporter, comprising amino acid residues 369-389. Additional support for this conclusion comes from studies in which [125I]APS forskolin was photoincorporated into the L-arabinose/H(+)-transport protein of Escherichia coli. Labelling of this transport protein was protected by both cytochalasin B and D-glucose. The region of the erythrocyte glucose transporter thought to be derivatized with IAPS-forskolin contains a tryptophan residue (Trp388) that is conserved in the sequence of the E. coli arabinose-transport protein. PMID- 2264822 TI - Mobilization of extracellular Ca2+ by prostaglandin F2 alpha can be modulated by fluoride in 3T3-L1 fibroblasts. AB - Changes in the intracellular concentration of calcium [( Ca2+]i) have been shown to mediate the physiological effects of certain agonists. Ca2+ mobilization occurs through multiple mechanisms which involve both influx and internal release of Ca2+. Prostaglandin F2 alpha (PGF2 alpha) caused a transient mobilization of intracellular Ca2+ in 3T3-L1 fibroblasts. This effect was characterized by fluorescence measurements of trypsin-treated cells loaded with fura-2/AM. In the absence of extracellular Ca2+, the peak amount of Ca2+ mobilized by PGF2 alpha was decreased by 70%, a lag time before the onset of [Ca2+]i increase was observed, and the rate of rise of [Ca2+]i was slowed. Addition of NaF (10 mM) to fura-2-loaded 3T3-L1 cells caused a dose-dependent increase in [Ca2+]i after a brief (approximately 10 s) lag. Maximal effects (approximately 300 nM) were observed at 5-10 mM-NaF. This effect was dependent on the presence of extracellular Ca2+ and appeared to be independent of inositol phosphate production. After reaching a peak at around 40 s after fluoride addition, [Ca2+]i returned to near-baseline within 120 s. This return of [Ca2+]i to near-baseline after fluoride stimulation and the inability of the cells to respond to a subsequent addition of fluoride indicated that the response to fluoride underwent desensitization. Similarly, the pathway used by PGF2 alpha to mobilize Ca2+ underwent desensitization. Exposure of the cells to a maximally effective concentration of fluoride and subsequent addition of PGF2 alpha produced a [Ca2+]i response to PGF2 alpha which was similar in magnitude and kinetics to that seen for PGF2 alpha in the absence of extracellular Ca2+. Conversely, prior exposure of cells to PGF2 alpha diminished the ability of fluoride to mobilize Ca2+. PGF2 alpha also increased inositol phosphate formation, with a time course and dose-response consistent with its ability to increase [Ca2+]i. Prior exposure of cells to fluoride did not change the time course or dose-response characteristics of PGF2 alpha-induced generation of inositol phosphates. These data suggest that PGF2 alpha and fluoride share a common mechanism of activating Ca2+ influx in 3T3-L1 cells. PMID- 2264823 TI - Acute effects of corticosterone on tissue protein synthesis and insulin sensitivity in rats in vivo. AB - The effect of corticosterone treatment on the sensitivity of muscle protein synthesis to insulin infusion was assessed in post-absorptive young rats. To select the optimal time period for corticosterone treatment, protein synthesis was measured by injection of L-[2,6-3H]phenylalanine (1.5 mmol/kg body weight) 1, 4, 12 or 24 h after injection of corticosterone (5 mg/kg body wt.). Muscle protein synthesis was significantly decreased at 4 h and the effect was maximal by 12 h; liver protein synthesis was elevated at 12 h and 24 h. The dose-response of muscle protein synthesis to a 30 min infusion with 0-150 munits of insulin/h was then compared in rats pretreated with corticosterone (10 mg/100 g body wt.) or vehicle alone. When no insulin was infused, corticosterone inhibited protein synthesis in gastrocnemius muscle. High doses of insulin stimulated protein synthesis, but the inhibition by corticosterone was similar to that in the absence of insulin. At intermediate doses of insulin there was an increased requirement for insulin to elicit an equivalent response in muscle protein synthesis. Plantaris muscle responded in a manner similar to that of gastrocnemius, but neither soleus muscle nor liver responded significantly to insulin. These data suggest that corticosterone has two modes of action; one which is independent from and opposite to that of insulin, and a second which causes insulin-resistance through a decrease in sensitivity rather than a change in responsiveness. PMID- 2264824 TI - Independent secretion of proteoglycans and collagens in chick chondrocyte cultures during acute ascorbic acid treatment. AB - The mechanisms regulating the secretion of proteoglycans and collagens in chondrocytes, in particular those operating at the level of the rough endoplasmic reticulum (RER), are largely unknown. To examine these mechanisms, I studied the effects of acute ascorbate treatment on the secretion of two collagen types (types II and IX) and two proteoglycan types (PG-H and PG-Lb, the major keratan sulphate/chondroitin sulphate proteoglycan and the minor chondroitin sulphate proteoglycan respectively in cartilage) in scorbutic cultures of chick vertebral chondrocytes. I found that the scorbutic chondrocytes synthesized underhydroxylated precursors of types II and IX collagen that were secreted very slowly and accumulated in the RER. When the cultures were treated acutely with ascorbate, both macromolecules underwent hydroxylation within 1-1.5 h of treatment, and began to be secreted at normal high rates starting at about 2 h. Proteoglycan synthesis and secretion, however, remained largely unaffected by ascorbate treatment. Both the half-time of newly synthesized PG-H core protein in the RER and its conversion into completed proteoglycan were unchanged during treatment. Similarly, the overall rates of synthesis and secretion of both PG-H and PG-Lb remained at control levels during treatment. The data indicate that secretion of types II and IX collagen is regulated independently of secretion of PG-H and PG-Lb. This may be mediated by the ability of the RER of the chondrocyte to discriminate between procollagens and proteoglycan core proteins. PMID- 2264825 TI - Homologous desensitization of ATP-mediated elevations in cytoplasmic calcium and prostacyclin release in human endothelial cells does not involve protein kinase C. AB - Single human umbilical-vein endothelial cells in culture loaded with the Ca2(+) sensitive dye fura-2 exhibited characteristic increases in cytosolic Ca2+ concentrations [( Ca2+]i) in response to extracellular ATP. The rapid decline of [Ca2+]i to prestimulated levels in the continued presence of ATP, with in most cells no sustained or oscillatory increase in [Ca2+]i, indicated desensitization. This was agonist-specific, and contrasted with the [Ca2+]i response to histamine, though each agonist mobilized Ca2+ from the same internal store. In populations of cells, when desensitization was variably induced by a second challenge with ATP after different times, desensitization of the initial peak [Ca2+]i was directly related to desensitization of prostacyclin release. This was not affected by treatment with the protein kinase C inhibitor staurosporine, under conditions where a similar degree of desensitization of peak [Ca2+]i induced by phorbol 12-myristate 13-acetate was blocked. Sequential addition of ATP to cell populations cumulatively desensitized the peak elevation of [Ca2+]i, but did not block the second, sustained, phase of the response. We conclude that desensitization of prostacyclin synthesis by ATP is likely to be due to uncoupling of the P2Y purinoceptor from phosphoinositidase C, but does not involve protein kinase C activation. PMID- 2264826 TI - Electron-transport components of the 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine delta 12-desaturase (delta 12-desaturase) in microsomal preparations from developing safflower (Carthamus tinctorius L.) cotyledons. AB - The major cytochrome in microsomal membrane preparations from developing seeds of safflower (Carthamus tinctorius, var High Linoleate), has a reduced-minus oxidized difference spectrum characteristic of a b-type cytochrome, and was identified from its midpoint-potential (E'7.2) value as cytochrome b5. Cytochromes P-450 and P-420 were also present. The cytochrome b5 content of microsomal preparations from a number of oilseed species was found to be in the order of 200-300 pmol/mg of protein. The cytochrome b5 was reduced in the membrane preparations by NADH, demonstrating the presence of an NADH: cytochrome b5 reductase; NADPH was a less effective donor. Microsomal membranes catalysed the NAD(P)H-dependent conversion of radioactive oleate into linoleate, indicating acyl-CoA: lysophosphatidylcholine acyltransferase and 1-acyl-2-oleoyl-sn-glycero 3-phosphocholine delta 12-desaturase (delta 12-desaturase) activity. Desaturation of oleate to linoleate was unaffected by CO, but inhibited by CN-. The addition of oleoyl-CoA to the NADH-reduced membranes resulted in the CN(-)-sensitive partial re-oxidation of cytochrome b5, indicating that electrons from NADH were transferred to the site of desaturation via this cytochrome. The delta 12 desaturase in safflower, therefore, is CN(-)-sensitive and appears to require cytochrome b5 and NADH: cytochrome b5 reductase for activity. PMID- 2264828 TI - Cell swelling inhibits proteolysis in perfused rat liver. AB - Exposure of isolated single-pass-perfused rat liver to hypo-osmotic media resulted in liver cell swelling and an inhibition of release of branched-chain amino acids. Similarly, cell swelling inhibited [3H]leucine release from perfused livers from rats in which liver proteins were prelabelled in vivo by intraperitoneal injection of L-[4,5-3H]leucine 16-20 h before the experiment. The effects of cell swelling on [3H]leucine release were fully reversible. [3H]Leucine release was also inhibited when cell swelling was induced by addition of glutamine (0.5-2 mM). There was a close relationship between the inhibition of [3H]leucine release and the degree of liver cell swelling, regardless of whether cell swelling was induced by hypo-osmotic perfusion or addition of glutamine. The data suggest that the known anti-proteolytic effect of glutamine is in large part due to glutamine-induced hepatocyte swelling. PMID- 2264827 TI - Effect of denervation on the expression of glycogen phosphorylase in mouse skeletal muscle. AB - After sciatectomy of the left hind-limb of C57BL/J mice, a denervation-induced muscular atrophy ensued and was accompanied by a decrease in the specific activity of glycogen phosphorylase to approx. 25% of control values. The cofactor of phosphorylase, pyridoxal 5'-phosphate, was used as a specific label in the determination of the degradation rate of the enzyme following nerve section. After a delay of 3-4 days, phosphorylase was degraded approx, twice as rapidly in the denervated gastrocnemius (0.20 day-1) as in the control muscle (0.12 day-1). The effect of denervation on phosphorylase mRNA was measured by quantitative Northern-blot analysis using a rat skeletal-muscle phosphorylase cDNA probe. After an initial rapid decline, phosphorylase mRNA levels stabilized in denervated muscle at 50% of the value measured in the contralateral control muscle. PMID- 2264829 TI - Inhibition of insulin secretion from rat islets of Langerhans by interleukin-6. An effect distinct from that of interleukin-1. AB - Glucose-induced insulin secretion from islets cultured in the presence of interleukin-6 (IL-6) for 12-24 h was inhibited to a similar extent as when islets were treated with interleukin-1 beta (IL-1 beta). However, unlike IL-1 beta, IL-6 did not potentiate insulin secretion during an acute (30 min) exposure of islets to the cytokine, nor did it inhibit DNA synthesis during a 24 h culture period. A 12 h pretreatment of islets with tumour necrosis factor-alpha (TNF-alpha) combined with IL-1 beta potentiated the inhibitory effect of IL-1 beta on secretion, such that 20 mM-glucose-induced insulin secretion was abolished. No synergistic inhibition of secretion was observed with TNF-alpha and IL-6. However, IL-1 beta and IL-6 were found to inhibit insulin secretion in an additive manner. These results suggest that IL-6 inhibits insulin secretion in a manner distinct from that of IL-1 beta, and that IL-6 is unlikely to mediate the inhibitory effects of IL-1 beta or TNF-alpha on rat islets of Langerhans. PMID- 2264830 TI - Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo. AB - The effect of administration of valproate on lipogenesis in the developing rat brain in vivo was studied. Valproate inhibited by 21-38% the rate of 3H2O incorporation into brain sterols, without significantly affecting fatty acid synthesis. Similarly, R-[2-14C]mevalonate incorporation into sterols was inhibited by 33-54%; the low rate of fatty acid synthesis under these conditions was not affected by valproate. Plasma ketone bodies decreased after treatment with valproate. Valproate inhibited (about 50%) both sterol and fatty acid synthesis in livers of weanling rats. It is concluded that valproate can specifically inhibit sterol synthesis in the brain during development, in part at a stage after mevalonate formation, and also by decreased exogenous precursor supply. PMID- 2264831 TI - Hyperinsulinaemia increases insulin action in vivo in white adipose tissue but not in muscles. AB - The effect of 4 days of stable hyperglycaemia and resulting hyperinsulinaemia on insulin-induced glucose utilization by individual rat tissues was studied in vivo. The treatment produced a net increase in the glucose utilization index under both basal and insulin-stimulated (euglycaemic/hyperinsulinaemic clamp) conditions in white adipose tissue. On the contrary, glucose utilization was unchanged in aerobic muscles but was decreased in glycolytic skeletal muscles during the clamp. PMID- 2264832 TI - Coupling of muscarinic receptors to the mobilization of intracellular Ca2+ stores in permeabilized SH-SY5Y human neuroblastoma cells. AB - Intracellular stores of Ca2+ were mobilized transiently by carbachol in suspensions of electrically permeabilized SH-SY5Y cells. The kinetics and the dose-dependence of this mobilization paralleled carbachol-induced increases in inositol 1,4,5-trisphosphate (InsP3) mass [for both parameters EC50 (concn. giving half-maximal response) = 60-70 microM]. Guanosine 5'-[gamma thio]triphosphate enhanced the maximal effect and the potency of carbachol on Ca2+ mobilization and InsP3 mass, but caused separation of the dose-response curves (EC50 = 0.6 microM and 5.6 microM respectively). These data show that functional coupling of muscarinic receptors to Ca2+ mobilization can be maintained after permeabilization, reveal major effects of guanine nucleotides on agonist-induced Ca2+ mobilization and provide a basis for explanation of discrepancies between agonist potency on InsP3 concentration and Ca2+ mobilization in intact cells. PMID- 2264833 TI - Maintenance of bile acid synthesis and cholesterol 7 alpha-hydroxylase activity in cultured rat hepatocytes. AB - Addition of foetal-bovine serum to rat hepatocytes cultured in Williams E medium resulted in improved maintenance of bile-acid-synthetic capacity and cholesterol 7 alpha-hydroxylase activity as compared with cultures supplemented with rat or newborn-bovine serum or cultures in a hormonally defined serum-free medium. Minimally, 5% (v/v) foetal-bovine serum was necessary to maintain these liver specific functions. Serum factor(s) responsible for these effects were not dialysable or associated with lipoproteins, but were removed by charcoal extraction. PMID- 2264834 TI - Parasite-induced processes for adenosine permeation in mouse erythrocytes infected with the malarial parasite Plasmodium yoelii. AB - In mouse erythrocytes harbouring the malarial parasite Plasmodium yoelii, three processes contributed to inward fluxes of adenosine, one of which is attributed to the native nucleoside transporter, because of the inhibitory effects of nitrobenzylthioinosine (NBMPR). New (parasite-induced) permeation processes of low NBMPR-sensitivity were (i) saturable fluxes with preference for the D enantiomer (D-Ado) and (ii) apparently unsaturable fluxes that proceeded by a channel-like route without enantiomeric selectivity. Parasite-induced fluxes of L and D-Ado were similarly inhibited by furosemide [IC50 (concn. causing half maximal inhibition) 15-17 microM], whereas D-Ado fluxes in uninfected erythrocytes were 10-fold less sensitive. PMID- 2264835 TI - Regulation of triacylglycerol biosynthesis in embryos and microsomal preparations from the developing seeds of Cuphea lanceolata. AB - Embryos of Cuphea lanceolata have more than 80 mol% of decanoic acid ('capric acid') in their triacylglycerols, while this fatty acid is virtually absent in phosphatidylcholine (PtdCho). Seed development was complete 25-27 days after pollination, with rapid triacylglycerol deposition occurring between 9 and 24 days. PtdCho amounts increased until day 15 after pollination. Analysis of embryo lipids showed that the diacylglycerol (DAG) pool consisted of mainly long-chain molecular species, with a very small amount of mixed medium-chain/long-chain glycerols. Almost 100% of the fatty acid at position sn-2 in triacylglycerols (TAG) was decanoic acid. When equimolar mixtures of [14C]decanoic and [14C]oleic acid were fed to whole detached embryos, over half of the radioactivity in the DAG resided in [14C]oleate, whereas [14C]decanoic acid accounted for 93% of the label in the TAG. Microsomal preparations from developing embryos at the mid stage of TAG accumulation catalysed the acylation of [14C]glycerol 3-phosphate with either decanoyl-CoA or oleoyl-CoA, resulting in the formation of phosphatidic acid (PtdOH), DAG and TAG. Very little [14C]glycerol entered PtdCho. In combined incubations, with an equimolar supply of [14C]oleoyl-CoA and [14C]decanoyl-CoA in the presence of glycerol 3-phosphate, the synthesized PtdCho species consisted to 95% of didecanoic and dioleic species. The didecanoyl glycerols were very selectively utilized over the dioleoylglycerols in the production of TAG. Substantial amounts of [14C]oleate, but not [14C]decanoate, entered PtdCho. The microsomal preparations of developing embryos were used to assess the acyl specificities of the acyl-CoA:sn-glycerol-3-phosphate acyltransferase (GPAT, EC 2.3.1.15) and the acyl-CoA:sn-1-acyl-glycerol-3 phosphate acyltransferase (LPAAT, EC 2.3.1.51) in Cuphea lanceolata embryos. The efficiency of acyl-CoA utilization by the GPAT was in the order decanoyl = dodecanoyl greater than linoleoyl greater than myristoyl = oleoyl greater than palmitoyl. Decanoyl-CoA was the only acyl donor to be utilized to any extent by the LPAAT when sn-decanoylglycerol 3-phosphate was the acyl acceptor. sn-1 Acylglycerol 3-phosphates with acyl groups shorter than 16 carbon atoms did not serve as acyl acceptors for long-chain (greater than or equal to 16 carbon atoms) acyl-CoA species. On the basis of the results obtained, we propose a schematic model for triacylglycerol assembly and PtdCho synthesis in a tissue specialized in the synthesis of high amounts of medium-chain fatty acids. PMID- 2264836 TI - Inhibitor studies indicate that active cathepsin L is probably essential to its own processing in cultured fibroblasts. AB - The lysosomal cysteine proteinase cathepsin L is synthesized in cultured mouse NIH 3T3 cells as a 39 kDa precursor and processed intracellularly into active 29 kDa and 20 kDa + 5 kDa lysosomal forms. Addition to culture media of the peptidyl aldehyde leupeptin, a non-covalent inhibitor of cathepsin L, results in the accumulation of the 20 kDa mature form of the enzyme, resulting in increased activity of cathepsin L as measured in an in vitro assay system in the absence of leupeptin. The more potent irreversible cathepsin L inhibitors benzyloxycarbonyl Phe-Ala-diazomethane and L-transepoxysuccinyl-L-leucylamino-(4-guanidino)butane, when added to living cells at low concentrations, result in accumulation of all partially processed forms of cathepsin L, especially the 29 kDa form, suggesting that cathepsin L is responsible for its own processing. Exogenous procathepsin L introduced into CHO cells by endocytosis via the mannose 6-phosphate receptor is processed in a manner similar to endogenous procathepsin L. We conclude that the major intracellular pathway for processing of procathepsin L, either endogenous or exogenous, probably requires active cathepsin L. PMID- 2264837 TI - Antibody organization on lipid films. Influence of pH and interchain disulphide reduction. AB - Two distinct lattice structures are observed for two-dimensional (2-D) antibody organization on phospholipid films. A low-order, small-unit-cell, square lattice is obtained at pH 7 and below for mouse IgE, mouse IgG2a and IgG2b and rabbit IgG. At pH 7.5 and above, the observed lattice structure switches to a large-unit cell, hexagonal type for rabbit IgG and mouse IgE. Interchain disulphide reduction by exposure to 2 mM-dithiothreitol results in the formation of the compact 2-D lattice for all cases and for all pH conditions. PMID- 2264838 TI - Application of electrical analogues for control analysis of simple metabolic pathways. AB - I have used electrical analogues for calculating the Flux Control Coefficients of metabolic pathways. An analogue circuit consists of resistances that are connected in series (or parallel) with a voltage (or current) source. In constructing the analogues, each of the enzymes in the pathway is associated with a resistance whose magnitude depends on the Elasticity Coefficients of the enzymes. These circuits can be designed in a heuristic fashion directly from the configuration of the pathway, without the necessity of writing down the governing equations with the use of Summation and Connectivity Theorems. The Flux Control Coefficients of the enzymes are represented by voltages across (or currents through) the resistances and are determined by an application of Ohm's Law. Results are given for (a) a simple linear pathway without feedback or feedforward regulation, and (b) a linear pathway with feedback inhibition. The analogue circuits are also convenient for assessing the relative importance of the various enzymes in flux control, and for simplifying the structure of a given pathway. PMID- 2264839 TI - Glycoprotein II from adrenal chromaffin granules is also present in kidney lysosomes. AB - Glycoprotein II (GP II) is a protein found in the membranes of chromaffin granules from adrenal medulla. Immunoblotting (one- and two-dimensional) revealed that this antigen is also present in liver and in kidney. Subcellular fractionation of the latter organ indicated that GP II was present in lysosomes. This was confirmed by immunoelectron microscopy. The antiserum against GP II immunolabelled the membranes of organelles which could be identified as lysosomes by the labelling of their contents with an antiserum against cathepsin D. Thus GP II is an antigen common to secretory vesicles and lysosomes. PMID- 2264840 TI - Identification and characterization of glucose transport proteins in plasma membrane- and Golgi vesicle-enriched fractions prepared from lactating rat mammary gland. AB - Plasma membrane- and Golgi vesicle-enriched membrane fractions were prepared from day-10 lactating rat mammary glands. Each fraction was found to contain a single set of D-glucose-inhibitable cytochalasin B-binding sites: plasma membranes and Golgi vesicles bound 20 +/- 2 and 53 +/- 4 pmol of cytochalasin/mg of membrane protein (means +/- S.E.M.), with dissociation constants of 259 +/- 47 and 520 +/- 47 nM respectively. Anti-peptide antibodies against the C-terminal region (residues 477-492) of the rat brain/human erythrocyte glucose transporter labelled a sharp band of apparent Mr 50,000 on Western blots of both fractions. Treatment with endoglycosidase F before blotting decreased the apparent Mr of this band to 38,000, indicating that it corresponded to a glycoprotein. Confirmation that this immunologically cross-reactive band was a glucose transporter was provided by the demonstration that it could be photoaffinity labelled, in a D-glucose-sensitive fashion, with cytochalasin B. Quantitative Western blotting studies yielded values of 28 +/- 5 and 23 +/- 3 pmol of immunologically cross-reactive glucose transporters/mg of membrane protein in the plasma membrane and Golgi vesicle fractions respectively. From comparison with the concentration of cytochalasin B-binding sites, it is concluded that a protein homologous to the rat brain glucose transporter constitutes the major glucose transport species in the plasma membranes of mammary gland epithelial cells. Glucose transporters are also found in the Golgi membranes of these cells, at least half of them being similar, if not identical, to the transporters of the plasma membrane. However, their function in this location remains unclear. PMID- 2264841 TI - Platelets and thrombolytic therapy. PMID- 2264842 TI - Elevated antinuclear antibody titers and the postpericardiotomy syndrome. PMID- 2264843 TI - Exercise capacity in coal workers' pneumoconiosis: an analysis using causal modelling. AB - Miners disabled from black lung disease (coal workers' pneumoconiosis, CWP) are entitled to disability benefits under United States federal and state laws. The determination of disability currently involves several scientific controversies. The Federal Department of Labor states that one second forced vital capacity (FEV1) is an important marker of disability from CWP. The Department of Labor also states that disability may occur in simple CWP, in the absence of progressive massive fibrosis (PMF). Both these contentions may reasonably be challenged. To investigate these issues, and to investigate the relation between exercise tolerance and several other variables, including age, weight, radiographic findings, and exposure to mining and smoking, we studied 690 miners. Simple correlation analysis was not helpful because many variables were correlated with each other. Linear regression analysis led to conclusions that were thought to be misleading. Causal modelling provided an analysis that appeared to be most explanatory. In the model tested years of coal mining did not affect FEV1; if this conclusion is substantiated by others FEV1 should be eliminated as an indicator of disability from CWP as it is not related to mining experience. On the other hand, the Department of Labor's position that disability may occur in simple CWP seems reasonable, as years of underground coal mining does affect forced vital capacity (FVC), which in turn impairs exercise capacity, even in the absence of PMF. FVC should be the major spirometric value used in determining disability from CWP because it alone is seen to decrease in relation to mining, and a decrease in FVC does affect exercise capacity. Thus this analysis addresses issues in determining black lung disability and shows the value of casual modelling. PMID- 2264844 TI - Intuition in critical care nursing practice. AB - Research that addresses intuition as experienced by nurses in critical care settings is rare; however, evidence to support the usefulness of intuition in making complex clinical decisions is mounting. The research reported here suggests that intuition is not a second-rate substitute for intelligent and rational decision-making; rather, it is a legitimate adjunct to empirical observation and linear analysis. PMID- 2264845 TI - Post-traumatic meningococcemia in a patient with deficiency of the C7 complement component. AB - A 20-year-old woman with C7 deficiency and fulminant meningococcemia that appeared after a blunt head trauma is described. This C7 deficiency was found in two of her siblings and should be suspected in patients presenting with neisserial infections. PMID- 2264846 TI - Marfan syndrome. What you need to know. AB - Marfan syndrome is a heritable disorder of the connective tissue. The major abnormalities occur in the ocular, skeletal, and cardiovascular systems, with variable expression in different patients. Most common are dislocated lens, which may or may not affect visual acuity, arachnodactyly, and mitral valve prolapse and aortic root dilatation. Cardiovascular complications cause about 90% of the excess early mortality seen with the syndrome. With proper management, including annual examination, some of the problems associated with these abnormalities may be avoided. The biochemical explanation for the disorder is not clear. Some investigators maintain that a defect in collagen is responsible, while others point to elastin as the culprit. Further studies are needed to disclose the exact defect; both proteins may be found to play a role in this highly variable disorder. PMID- 2264847 TI - A technique for blepharoplasty without incising or "puncturing" orbital septum. AB - A blepharoplasty procedure is described in which the actual dissection and removal of adipose tissue has been replaced simply with unipolar electrodesiccation. PMID- 2264848 TI - Surviving a crash landing: a software review. PMID- 2264849 TI - [Annulo-aortic ectasia]. AB - On the basis of a literature review and the study of 18 cases, the authors examine annuloaortic ectasia, which involves dilatation of the fibrous ring of the heart at the aortic orifice, marked by aortic regurgitation and dystrophic aneurysm of the ascending aorta. The authors noted a predominantly muscular disorder (14 males, 4 females) often detected from an assessment of aortic regurgitation without clinical, radiologic or specific electrical features. The value of echocardiography and Doppler echocardiography is clearly apparent from the diagnosis of the disease, monitoring of progress, selection of patients for invasive pre-operative explorations and post-operative surveillance. The developing gravity of this disease is stressed, rapid repercussions in the left ventricle intervening more than complications due to ectasia itself. This indicates the urgency of complete replacement of the whole ascending aorta and of the aortic valve with reimplantation of coronary arteries as in the Bentall or Bentall-Cabrol surgical intervention, seven cases of which have been reported with satisfactory results. PMID- 2264850 TI - Coming of age in nursing. Rethinking the philosophies behind holism and nursing process. AB - No one is going to like everything that Kobert and Folan say in this article, but it offers a rich bouquet of ideas for discussion and debate. Are they right to assert that holism and nursing process are incompatible? That nursing process is associated with an immature level of professional development? That holism is the answer for nursing? That holism equates with feminism while nursing process represents a masculine reductionism? PMID- 2264851 TI - Mammography and breast cancer. PMID- 2264852 TI - Confusing serological abnormalities in bird fancier's lung. PMID- 2264853 TI - Organ donation. I--Management of the multiorgan donor. PMID- 2264854 TI - Decubitus ulcers. PMID- 2264855 TI - Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears. AB - OBJECTIVE: To determine the efficacy and morbidity of fine loop diathermy excision of the cervical transformation zone as applied to the management of outpatients with abnormal cervical smears. DESIGN: Prospective programme trial with six month follow up. SETTING: Two hospital based colposcopy clinics. PATIENTS: 616 Patients aged 16-60 with abnormal cervical smears. INTERVENTIONS: After colposcopic and cytological assessment excision of the cervical transformation zone by fine loop diathermy under local anaesthesia in the outpatient department. MAIN OUTCOME MEASURES: Time to complete the treatment, immediate morbidity in terms of discomfort and bleeding, and cytological and colposcopic findings at six months. RESULTS: Treatment was completed in a mean of 3.47 minutes (SD 1.99). Immediate morbidity was minimal, and histological specimens were adequate in over 90% of cases. Almost two thirds of patients were treated at their first visit to the clinic. 58 Patients (9.4%) failed to attend for follow up at six months and one had had a hysterectomy. Of the 557 patients who attended for colposcopic and cytological follow up at six months, 506 (91%) were normal cytologically and 19 (3.4%) had histologically confirmed persistence of cervical intraepithelial neoplasia. The overall confirmed failure rate of the technique was 4.4%. CONCLUSION: Loop diathermy excision is an effective treatment with low morbidity and is an appropriate modality for patients with abnormal cervical smears. PMID- 2264856 TI - Cotswolds modification of the Ann Arbor staging system for Hodgkin's disease. PMID- 2264857 TI - Plasma amino acid concentrations re type of feeding. PMID- 2264858 TI - Platelets and thrombolysis. PMID- 2264859 TI - Colic. PMID- 2264860 TI - Anesthesia for microlaryngeal laser surgery. PMID- 2264861 TI - Corticosteroids and bone mass. PMID- 2264862 TI - Perceptions of pain relief after surgery. PMID- 2264863 TI - Diagnosing pulmonary embolism. PMID- 2264864 TI - Prevention of recurrent pulmonary embolism. PMID- 2264865 TI - Polygenic heredity of porphyria cutanea tarda. PMID- 2264866 TI - Etretinate-resistant Darier's disease. PMID- 2264867 TI - Interexaminer concordance in detecting joint-play asymmetries in the cervical spines of otherwise asymptomatic subjects. PMID- 2264868 TI - Septic shock following infected Haemaccel. PMID- 2264869 TI - Vitamin D metabolism in Mexican-Americans. PMID- 2264870 TI - Diagnosis, incidence, and prevention of congenital toxoplasmosis. PMID- 2264871 TI - Land ambulance vs helicopter for interhospital transfer. PMID- 2264872 TI - Treatment-resistant depressives. PMID- 2264873 TI - "Intuition in critical care nursing practice". PMID- 2264874 TI - Anterior Zielke instrumentation for spinal deformity in adults. PMID- 2264875 TI - Treatment of varicose and telangiectatic leg veins with hypertonic saline. PMID- 2264876 TI - MR imaging of lateral disc herniation. PMID- 2264877 TI - Ribavirin: a role in HIV infection. PMID- 2264878 TI - Raising the collective consciousness. PMID- 2264879 TI - Live exports. PMID- 2264880 TI - Denitrogenation, the 5% solution. PMID- 2264881 TI - Awareness, caesarean section and the isolated forearm technique. PMID- 2264882 TI - Continuous brachial plexus blockade. PMID- 2264883 TI - Should hypercholesterolemia in the elderly be treated? PMID- 2264884 TI - Infection and Cell-Saver use. PMID- 2264885 TI - Seasonal variation in stroke frequency. PMID- 2264886 TI - Acute changes in renal function associated with deferoxamine therapy. PMID- 2264887 TI - Complement deposits in inflammatory bowel disease. PMID- 2264888 TI - Helicobacter pylori infection and atrophic gastritis in the elderly. PMID- 2264890 TI - The headless human. PMID- 2264891 TI - Mental health and the elderly. Special needs, special skills. PMID- 2264892 TI - Outerbridge's ridges. PMID- 2264889 TI - A selective defect of interferon alpha production in human immunodeficiency virus infected monocytes. AB - Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN beta were not detected nor was the mRNA expressed in either uninfected or HIV infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN omega produced by infected cells. The markedly diminished capacity of HIV infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes. PMID- 2264893 TI - Arthroscopic anatomy of the hip. AB - The arthroscopic anatomy of the hip has been studied using a number of portals. Both distraction and positioning are necessary to allow insertion of instruments, and to allow exposure of the important anatomical structures. The internal anatomy of the hip joint is described in detail based on the arthroscopic view from the different portals. This study helps orient those interested in arthroscopy of the hip. PMID- 2264894 TI - SLAP lesions of the shoulder. AB - A specific pattern of injury to the superior labrum of the shoulder was identified arthroscopically in twenty-seven patients included in a retrospective review of more than 700 shoulder arthroscopies performed at our institution. The injury of the superior labrum begins posteriorly and extends anteriorly, stopping before or at the mid-glenoid notch and including the "anchor" of the biceps tendon to the labrum. We have labeled this injury a "SLAP lesion" (Superior Labrum Anterior and Posterior). There were 23 males and four females with an average age of 37.5 years. Time from injury to surgery averaged 29.3 months. The most common mechanism of injury was a compression force to the shoulder, usually as the result of a fall onto an outstretched arm, with the shoulder positioned in abduction and slight forward flexion at the time of the impact. The most common clinical complaints were pain, greater with overhead activity, and a painful "catching" or "popping" in the shoulder. No imaging test accurately defined the superior labral pathology preoperatively. We divided the superior labrum pathology into four distinct types. Treatment was performed arthroscopically based on the type of SLAP lesion noted at the time of surgery. The SLAP lesion, which has not been previously described, can be diagnosed only arthroscopically and may be treated successfully by arthroscopic techniques alone in many patients. PMID- 2264895 TI - Effects of abrasion therapy on tears in the avascular region of sheep menisci. AB - This study was designed to test the hypothesis that abrasion of the parameniscal synovium aids healing of a stable tear in the avascular region of the meniscus in a sheep model. In six sheep, a 5-7-mm longitudinal full-thickness tear was made in the avascular inner half of the anterior part of the lateral meniscus. The parameniscal synovium was abraded superiorly and inferiorly from the meniscus periphery to the lesion. Three animals in a control group received identical meniscal tears but no abrasion treatment. A harness prevented weight bearing and maintained the knee fully flexed after surgery. Twelve weeks after the operation, no healing was seen in any tears. Histologic examination revealed in both groups increased numbers of dividing chondrocytes on either side of the tear. In the test group, several layers of fibroblasts, which appeared in two menisci to derive from the upper meniscal surface, were seen covering both cut surfaces of the tear. It is concluded that the distance from the periphery to the defect is too far for abrasion therapy to stimulate sufficient cellular ingrowth to facilitate repair of tears in the avascular region of the meniscus. PMID- 2264896 TI - Endoscopic release of the carpal ligament for carpal tunnel syndrome: 22-month clinical result. AB - This article represents a review of 149 carpal tunnel decompressions on 109 carpal tunnel syndrome patients, and a 22-month clinical result on endoscopic carpal ligament release. The symptoms were relieved and no permanent nerve damage, vascular complications, hematomas, infections, or recurrences were reported. Postoperatively, one patient had a temporary loss of the interosseous muscle but recovered spontaneously in 4 weeks. In this 22-month survey, 28.9% of the patients were able to return to normal activities and work within 1 week, 58.5% returned within 2 weeks, 75.4% returned within 3 weeks, and 85.9% returned within 4 weeks. A pinch-and-grip study was performed; 32% regained normal pinch and-grip strength within 1 week, 74% regained it in 2 weeks, 93% regained it in 3 weeks, and 100% regained it in 4 weeks. Based on our results, there has been rapid recovery, less scarring, decreased postoperative pain, and no loss of pinch and-grip strength. PMID- 2264897 TI - Anatomy of the supraclavicular fossa portal in shoulder arthroscopy. AB - Because of the need for a third portal for operative procedures during glenohumeral joint arthroscopy, we studied the anatomy of the supraclavicular fossa portal with the humerus in various degrees of abduction and the trochar placed at various angles. Our purpose was to establish a "safe zone" of introduction that would avoid damage to the tendinou portion of the rotator cuff. Eight shoulder specimens were studied. Sharp- and blunt-tipped 4-mm trocars were used to enter the joint. The trapezius was penetrated at all angles of humeral abduction and trocar angulation. The trocar penetrated the tendinous portion of the rotator cuff in all specimens at 90 degrees of abduction, seven of eight specimens at 70 degrees, six of eight specimens at 60 degrees, and three of eight specimens at 45 degrees of abduction. No penetration of the musculotendinous portion occurred when the arm was in 30 degrees of abduction or at the side. When it is necessary to use the supraclavicular portal, traction should be released and the humerus should be brought down to at least 45 degrees. The trocar should be introduced laterally at 30 degrees and angled slightly posteriorly to avoid the tendinous portion of the rotator cuff. PMID- 2264898 TI - An anatomical study of the suprascapular nerve. AB - The course of the suprascapular nerve and its distance from fixed scapular landmarks were measured in 90 cadaveric shoulders. In an additional 15 cadavers, three pins were passed at various angles in a general anterior-posterior direction through the middle of the glenoid neck just inferior and lateral to the base of the coracoid process. The distance between the exit site on the posterior glenoid neck and the suprascapular nerve at the base of the scapular spine was recorded for each pin. Inferiorly directed pins were the furthest from the suprascapular nerve and averaged 16 mm. On the basis of these data, a relative safe zone is described in the posterior glenoid neck. Knowledge of the anatomic course of the suprascapular nerve may aid the physician in the diagnosis and treatment of suprascapular neuropathies. Appreciation of the safe zone may help the shoulder surgeon avoid iatrogenic injury to the suprascapular nerve during arthroscopic Bankart procedures and other open surgical procedures requiring dissection of the posterior glenoid neck. PMID- 2264899 TI - Arthroscopic surgery of the knee under local anesthesia. AB - This report delineates the efficacy of local anesthesia in the performance of arthroscopic surgery of the knee. A retrospective review of 500 cases revealed that only three required administration of general anesthesia to successfully complete the procedure. A prospective study comparing fentanyl, midazolam, and fentanyl/midazolam combinations as intravenous supplements was performed. Meticulous surgical technique combined with local anesthesia and some form of intravenous sedation in minimal therapeutic dosage will provide satisfactory conditions to perform surgical arthroscopy of the knee. PMID- 2264900 TI - The development of synovial plicae in human knee joints: an embryologic study. AB - An embryologic study about the development of the human knee joint cavity was carried out with special attention to the formation of synovial plicae, using a total of 116 knees of embryos and fetuses. The incidence of synovial plicae in the fetal stage was also investigated. Formation of joint space starts at the middle of the interzone at around 8 weeks of gestation. Multiple small cavitations around the femoral condyle and patella coalesce to form larger cavitations. At around 10 1/2 weeks, the knee joint consists of a single cavity with synovial lining. At certain sites, such as at the medial part of patello femoral and the infrapatellar regions, mesenchymal tissue strands remain. They may become plica. In the fetal stage from 11 to 20 weeks, an infrapatellar plica was found in 50% of specimens, a suprapatellar plica in 33%, and a mediopatellar plica in 37%. Only the infrapatellar plica showed a decrease in incidence. PMID- 2264901 TI - Intra-articular ganglia in the knee. AB - Thirty-eight intra-articular ganglia were found in knees that were painful or had the symptoms of a mechanical derangement. During the period of study, 6,500 knees were examined arthroscopically by one surgeon. Thirty-five of the ganglia arose at the insertions of the cruciate ligaments. Excision of the ganglion yielded excellent results in 22 knees, good in 14, and fair in one. PMID- 2264902 TI - Arthroscopic removal of painful Bristow hardware. AB - Complications of metallic hardware about the shoulder have been well documented in the literature. This case report presents a recreational athlete who presented to our office with a painful shoulder 4 years after a Bristow procedure. Radiographic imaging confirmed contact of the humeral head on the Bristow screw. In these unusual situations, arthroscopic evaluation, as this case suggests, should be considered. The patient's hardware was removed arthroscopically, obviating an open procedure and hospitalization. PMID- 2264903 TI - A suture "retractor": a technical aid for bucket-handle meniscal resections. AB - Meniscal repair, healing, and survival have been demonstrated in the literature. Meniscal preservation is, however, not always possible. We present a technique that may aid the surgeon in difficult bucket handle resections by stabilizing a portion of the meniscus with a "suture retractor" prior to resecting either a posterior or anterior meniscal horn. This technique may also be modified to prepare the inner rim when one is performing meniscal repair. PMID- 2264904 TI - Deep venous thrombosis after shoulder arthroscopy. PMID- 2264905 TI - [Tracheal stenosis as initial symptom of a polychondropathy]. AB - A survey of literature dealing with relapsing polychondritis is given hinting at an autoimmune etiology. Two cases with mainly laryngotracheal symptoms are discussed. A new hypothesis about pathogenesis has not been found. PMID- 2264906 TI - [Unilateral reconstruction of the anterior neck using a combination flap technique]. AB - This technique is recommended for the one-stage reconstruction of the cervical esophagus, for the protection of the cervical vessels by soft tissues and for the substitute of the anterior neck skin. The microvascular free jejunal flap is transplanted and then covered by the myocutaneous pectoralis-major-island-flap. Indications are complete defects of the anterior neck after the resection of tumors, after the resection of necrotic tissues following radionecrosis, when all soft tissues in front of the prevertebral fascia have to be resected. Details of the surgical technique are explained. This combination flap technique proved to be useful in 4 patients without any complications. PMID- 2264907 TI - [Conservative correction of congenital deformities of the auricle]. AB - Congenital deformities of the shape of the auricle may be corrected with a nonsurgical procedure by means of temporary splinting with dental material and surgical tapes (steri-strips) as reported elsewhere. If the dressing was performed during the first three days of life the aesthetic results achieved were persistent and made a posterior surgical correction unnecessary. The elasticity of the ear cartilage seems to be related to the levels of estrone and estradiol. PMID- 2264908 TI - [Studies on the local defense reactions of the nasal mucosa in employees in Rostock harbor exposed to large amounts of dust]. AB - Defense mechanisms of the nasal mucosa are characterised by resistance and immunity processes. Secretory IgA seems to be very important for immune response. The aim of our work was to clarify whether the concentration of S-IgA in nasal secretion was influenced by extreme exposure of dock workers to dust. We investigated the nasal fluid of both the septum and the turbinate mucosa of 75 dock workers compared with 12 controls. A decrease of S-IgA concentration in the nasal fluid was seen after the work. This decrease differed for the various types kinds of dust and was significant (p less than 0.05) for apatite, urea and potash. A reduction of S-IgA was also seen after exposure for a longer time (several years). Dockers with repeated infections do not have decreased S-IgA values. These investigations make a contribution to the immune response in the nasal mucosa. PMID- 2264909 TI - [Laryngeal carcinoma and asbestos exposure. A critical review of the literature]. AB - Based on a comprehensive review of the literature with special reference to methodology of the studies, the author observes a causality between laryngeal carcinoma and occupational asbestos exposure. It is suggested that under special circumstances a laryngeal carcinoma should be approved as an occupational disease in relation to asbestos exposure in the Federal Republic of Germany. PMID- 2264910 TI - [Anamnesis and polysomnography in patients who snore and in obstructive apnea syndrome: a comparative study in 140 patients]. AB - Results of a questionnaire comprising 23 questions concerning general data, snoring, and daytime sleepiness were compared with polysomnographic data. 140 consecutive patients, 89 of them chronic snorers and 51 with obstructive sleep apnea syndrome (OSAS) were included in the study. The results show that ten questions, four about snoring and six about daytime sleepiness, are sufficient cause to suspect of OSAS in a snoring patient. This patient should be diagnosed and treated immediately. PMID- 2264911 TI - [Lipomatous atrophy of the parotid gland in chronic alcohol consumption]. AB - The effect of chronic ethanol consumption on the morphology of the rat parotid gland was investigated. After feeding an ethanol diet containing 36% of total calories as ethanol for 90 days light microscopic and electron microscopic investigations of the parotid gland tissue showed a striking fat accumulation compared to control rats. Besides interstitial fat tissue dispositions, fat droplets of various size occurred in most of the acinar cells. Additional morphometric investigations revealed a decrease in mean acinar cell volume ( 21.9% p greater than 0.001). The latter finding reflects an atrophy of the secretory parenchyma and appears to be responsible for the impaired saliva secretion after chronic ethanol consumption which has been observed in former studies. PMID- 2264912 TI - [Immuno-diagnostic findings in "secondary" Sjogren syndrome in chronic polyarthritis]. AB - In order to characterize typical findings in patients (pts.) with secondary Sjogren's Syndrome (SS) associated with rheumatoid arthritis (RA), 173 patients with RA were studied. Pathological screening-test results (Schirmer- and Saxon test) were followed by ENT- and ophthalmological investigations and examinations in the field of internal medicine. Secondary SS associated with RA was diagnosed in 34 pts. (20%). Immuno-serological SS-A and/or SS-B-antibodies were found in 11 (32%) of 34 patients. 9 pts. (27%) had antinuclear antibodies. Abnormal titers of circulating immune complexes were present in the sera of 24 pts. (71%), salivary gland-antibodies in 3 pts. (9%). In 16 of 34 pts. (47%) minor salivary gland biopsy was performed. Lympho-plasma cell sialadenitis could be verified in all pts. Immuno-histological reactions to anti-IgG and/or anti-IgM and/or anti-IgA were detected in 10 (62%) of 16 pts. We could not find a single criterion to ascertain the diagnosis SS which still has to be made by considering all clinical and serological findings. Immunological findings may provide helpful and interesting diagnostic aspects which by long term observation may even gain importance; however, no differential therapeutic consequences can be seen at the moment. PMID- 2264913 TI - [Graphic representation of the results of ENG-calorization using a BASIC program]. PMID- 2264914 TI - Kapiolani transport nurses speak out. PMID- 2264915 TI - [Environment of the asthmatic child]. AB - This work is in the purview of epidemiological studies that concern the environment of asthmatic children. Infantile asthma is found especially in children who live in the country, in an electrically-heated house and who sleep in a badly orientated room. The environment is composed of feather-bedding, soft toy animals and animals from the countryside. The role of tobacco and insufficient aeration has been shown in this enquiry. School attendance is not disturbed by development of asthma. The majority of teachers do not understand infantile asthma. This study is to emphasize the importance of the environment in the development of allergic infantile asthma and the possibilities of its prevention. Information to the teachers, as well as the treating physicians, is also necessary for prevention. PMID- 2264916 TI - [Food allergy in childhood asthma]. AB - Food allergy is responsible for asthma in 6% of cases, all ages together, with the same etiology. As in a adults, the influence of atopy is indisputable and is proved by the presence of familial and personal antecedents and rise in total IgE. Proof of food allergy is based only on tests of exclusion and reintroduction and/or provocation tests, under control of spirometry and plasma histamine. Eggs, milk, wheat, fish, potato, pork meat are the foods most frequently associated. A comparative study of food allergy in adult asthma shows that cow milk and eggs are most frequently responsible, as in children. For diagnosis, specific IgE RAST is more often correlated (65%) with the clinical condition than skin tests (60%). PMID- 2264917 TI - Acute care of mild to moderately severe asthma in 1990. AB - When considering the acute treatment of mild to moderately severe asthma in the outpatient or emergency room setting, the author indicates how older, effective modalities of care can be replaced with modalities which are at least as effective but also teach the patient how to care for himself. Older approaches including epinephrine injections, intravenous aminophylline, intravenous superhydration, nebulizer-generated aerosols, and oxygen have the disadvantage of binding the patient to the emergency room for future attacks. By stressing proper use of sympathomimetic metered-dose inhalers (often with a spacer), oral theophyllines, oral B-2 agonists, oral and inhaled corticosteroids, the 90% of patients well enough to go home after treatment will have had a lasting educational experience designed to increase their self-reliance and make further ER visits unnecessary. PMID- 2264918 TI - [Accident in a synoviorthesis with osmic acid]. PMID- 2264920 TI - Radiography in Spain. PMID- 2264919 TI - The establishment of dose reducing protocols using rare earth filters in paediatric radiography. PMID- 2264921 TI - Suspected foreign body on the lateral neck radiograph--pitfalls in interpretation. PMID- 2264922 TI - Gastroscopy and ultrasound guided pancreatic cyst drainage. PMID- 2264923 TI - MRI guided biopsy for differentiation of radiation changes and recurrent tumour. PMID- 2264924 TI - Computers and the radiographer. PMID- 2264925 TI - Effect of cis-platinum on heme, drug, and steroid metabolism pathways: possible involvement in nephrotoxicity and infertility. AB - cis-Platinum, a coordination complex of platinum, is highly effective against a number of human tumors, including steroid-dependent tumors such as testicular and prostatic cancers. It is generally assumed that DNA is the cellular target responsible for the antitumor activity of the drug. Much evidence, however, has been gathered in recent years suggesting that cis-platinum has major effects on the endocrine system, particularly the hypothalamic-pituitary-testis steroidogenesis axis, and severely disrupts the normal production of testosterone. In the axis, testis is the prime target, where the LH receptor binding capacity of Leydig cells is decreased by nearly 80%. Within the testis, the mitochondrial cytochrome P-450scc and side-chain cleavage activity are markedly depressed and the microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration are decreased; side-chain cleavage activity is rate-limiting in testosterone production. The effects are not limited to the testis cytochrome P-450, but extend to other organs including the liver and the kidney cytochromes. In the liver, a feminization of the cytochromes P-450 profile is produced, and hence the biotransformation of endogenous steroids as well as that of exogenous chemicals is affected. In the kidney, cis-platinum appears to be the most effective inducer of cytochrome P-450, whereby the biotransformation of the prostaglandins and fatty acids could be altered. The spectrum of the effects of cis-platinum on cytochrome P-450-dependent drug metabolism and steroid hydroxylation activity mimic those produced by hypophysectomy and are for the most part reversed by the anterior pituitary hormones. These findings suggest the possibility that general feminization of steroidogenesis caused by cis-platinum may significantly contribute to the activity of cis-platinum against hormone dependent tumors. PMID- 2264926 TI - The toxicity of inhaled methanol vapors. AB - Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor. PMID- 2264927 TI - Efficient gene transfer in live mice using a unique retroviral packaging line. AB - Irradiated mice were transplanted with cells containing a foreign gene to evaluate gene transfer and expression as a model for gene therapy. Using a uniquely safe and efficient retroviral packaging line developed in this laboratory (GP + E86), we demonstrate efficient and safe long-term transfer of the neomycin resistance (neoR) gene into mice. By infusing cells obtained from spleen colonies of primary post-transplant mice marked with the neoR gene into irradiated recipients, secondary and tertiary generations of recipient mice were produced. There was very low reconstitution activity of single stem cells in these successive generations of mice. We conclude that many more than one stem cell is necessary for successful long-term bone marrow transplantation in mice, presumably as a result of the relatively low frequency of stem cell cycling. PMID- 2264929 TI - A family of homologous X chromosomal sequences with some members showing evidence of enhancer activity. AB - Little is known about either the frequency of occurrence of enhancers or the interrelationships of various enhancers in mammalian genomes. Previous reports described a potent, transcriptional enhancer within the sequence termed "Xrep," a human X chromosomal genomic clone (Riley et al., 1986; Riley, 1989a). Additional Xrep-related sequences reside on the human X chromosome. A probe for the Xrep enhancer hybridized with multiple restriction fragments located on the X chromosome. Two of the fragments cross-hybridizing with the enhancer had identical enhancer-like sequences but dissimilar flanking sequences. However, both of the sequenced enhancers were flanked by poly(GT) repeats strongly implicated in the generation of polymorphisms. A third sequence cross-hybridizing to the enhancer probe was found, in chromatin form, to be extremely DNase I hypersensitive. PMID- 2264928 TI - Mouse plasma kallikrein: cDNA structure, enzyme characterization, and comparison of protein and mRNA levels among species. AB - There is differential regulation of liver mRNA levels of rat (r) and mouse (m) plasma kallikrein (PK), as observed on Northern blots. Affinity purification of mPK and rPK, microsequencing, and radioimmunoassay in either rat or mouse showed that the difference in mRNA levels does not appreciably affect the circulating PK concentration. Nuclear run-off assays demonstrated that the regulation of the mRNA level of PK is post-transcriptionally controlled. Complete cDNA sequence determination of mPK was achieved using a combination of polymerase chain reaction and lambda gt11 library screening procedures. Within the coding region, the overall sequence homology between mPK and rPK is about 91-92% in amino acid and nucleotide sequence. Although the 3' noncoding segment of mPK is shorter than that of rPK, we calculate a 53% homology with a 5% higher A/T content for mPK. The largest difference is found at the 5' end of the mRNAs: whereas rPK is predicted from its gene structure to have a 167-nucleotide leader sequence, mPK is expected to have more than 605 nucleotides, of which the last 291 are very similar to those found in the rPK gene. The regulation of the mRNA stability and/or turnover rate of PK may possibly be affected by its 5' end in a species dependent manner. PMID- 2264930 TI - Decreased Hnf-1 gene expression in mice homozygous for a 1.2-centiMorgan deletion on chromosome 7. AB - The mammalian CYP2E1 gene encodes a cytochrome P450 enzyme that is markedly increased soon after birth. In vitro evidence suggests that the rat CYP2E1 gene is positively regulated by the transcription factor HNF-1 or a protein displaying DNA-binding properties similar to HNF-1. In contrast to newborn wild-type mice and mice heterozygous for a 1.2-centiMorgan deletion on chromosome 7, newborn mice homozygous for this deletion do not show significant expression of the Cyp2e 1 and Hnf-1 genes. However, the Cyp2e-1 and Hnf-1 structural genes are not in the chromosome 7 segment deleted in these mice. Although Cyp2e-1 maps to chromosome 7, it is distal to this deletion; Hnf-1 maps to chromosome 5. These data suggest that the deleted region of chromosome 7 contains a gene encoding a trans-acting factor which is upstream (epistatic) in the regulatory cascade that includes Hnf 1 gene expression. PMID- 2264931 TI - A simplified method for the preparation of transcriptionally active liver nuclear extracts. AB - We have developed a simplified method for the preparation of liver nuclear extracts to study gene regulation and protein-DNA interactions. This protocol uses conventional laboratory equipment and standard reagents. The liver tissue is homogenized in a low-salt solution at physiological molarity with subsequent adjustment of the molarity and purification of nuclei by density sedimentation. The nuclear extracts are transcriptionally active in a validated cell-free transcription assay and contain functional DNA-binding proteins. This protocol results in the rapid preparation of highly reproducible and active liver nuclear extracts. PMID- 2264932 TI - Defining target sequences of DNA-binding proteins by random selection and PCR: determination of the GCN4 binding sequence repertoire. AB - We developed a simple and accurate method to define the sequence recognition properties of DNA-binding proteins. The method employs polymerase chain reaction (PCR) amplification of sequences selected from a mixture of random oligonucleotides by the gel mobility-shift assay. We used this method to define the sequence requirement of the binding domain of the yeast transcriptional activator GCN4. Using a total of 200 ng of purified protein and four cycles of binding and subsequent amplification, we identified the TGA-(C/G)TCA sequence as the binding consensus of GCN4, which is consistent with the previously reported recognition sequence. In addition, our data indicate that GCN4 can bind with lower affinity to sequences that differ from the optimal sequence in one or even two positions. The most common variation was the C to A at position +2. The majority of the substitutions that still allowed binding were 3' to the central C residue indicating that the two sides of the palindromic recognition sequence are not equivalent. PMID- 2264933 TI - cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases. PMID- 2264934 TI - Markers of exposure to diesel exhaust in railroad workers. AB - Diesel exhaust is a known mutagen and a potential human carcinogen. Recent epidemiological studies have demonstrated a small increase in the risk of lung cancer from diesel exhaust exposure. However, many epidemiological studies have used crude estimates of exposure, and even accurate measures of exposure may not be accurate estimates of the internal dose received. Measurement of diesel exhaust exposure also has been limited by the absence of a standard marker. This study was undertaken to evaluate the usefulness of urinary mutagenicity as a biological marker of diesel exhaust exposure in the workplace. We measured the exposure of individual railroad workers to diesel exhaust by using personal air samples taken over two consecutive work shifts. Nicotine in the samples was measured to adjust the respirable particle concentrations for active and passive cigarette smoking. Urine samples were collected at the end of the study work shifts and were analyzed for markers of cigarette smoking (nicotine, cotinine) and for mutagenicity, using a sensitive microsuspension assay (micro preincubation assay; Salmonella strain TA98 with or without S9 enzyme). The number of cigarettes smoked on the study shift was recorded, and subjects completed a questionnaire at the end of the second day on personal habits and exposures at home and work. Multiple regression analyses were used to analyze independent determinants of urinary mutagenicity, including a generalized least squares analysis that divided residual variation into between- and within-person components. Eighty-seven subjects completed 151 two-day protocols; an additional four subjects provided usable data for a single day (n = 306 samples). Respirable particle concentration was not a good marker of diesel exhaust exposure when contamination by environmental tobacco smoke existed in the work location, but respirable particle concentration that was adjusted for environmental tobacco smoke correlated with a priori assessments of diesel exhaust exposure by job grouping. Phenanthrene concentration, as a potential marker, was measured in a subset of personal samples, and correlated with known diesel exhaust exposure by job grouping. A constant ratio of phenanthrene to respirable particles in area samples from diesel exhaust-exposed work locations suggested that phenanthrene is promising as a marker for diesel exhaust. Mutagenic activity was also measured from extracts of respirable particles in a few personal filter samples, and this technique may be useful for further investigation in epidemiological studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2264935 TI - Water structure at interfaces: the present situation. AB - This paper discusses the structure of adsorbed water at interfaces. It begins with a review of the development of the research, then examines and compares some of the most important models in this field. The results of recent spectroscopic work, especially those of IR spectroscopy, are discussed and applied to the selection of the most probable model. PMID- 2264936 TI - Transcultural Nursing Society. PMID- 2264937 TI - Use of selected nursing diagnoses: a transcultural comparison between Mexican and American nurses. AB - While use of nursing diagnoses has increased both in the United States and abroad, there have been few reports on the use and applicability of the diagnostic categories across culturally distinct populations. The authors report a preliminary study which compared the use of selected diagnostic categories in an American group and a Mexican group of nurses. Data indicate that nurses did not demonstrate consistency with one another in use of diagnoses either within each group or between groups. The authors caution that further study and documentation of how diagnoses are understood and used by practitioners is needed before widespread international or transcultural usage in encouraged. PMID- 2264938 TI - The immigrant Haitian mother: transcultural nursing perspective on preventive health care for children. AB - Thirty immigrant Haitian mothers in Southeast Florida were interviewed regarding their beliefs and practices about preventive health care (illness prevention and health maintenance measures) for infants and preschool children (up to age 5). All mothers used preventive health care measures from both the Western biomedical and traditional Haitian ethnomedical (folk) systems. Ninety-seven percent used magico-religious measures; 47% administered home remedies; 47% gave children over the-counter drugs; and 35% utilized a variety of measures to ensure cold air did not enter neonates and cause illness or pain. The Haitian mothers considered the preventive health care measures effective because the children remained healthy and will likely use them again. They sought consultation from a variety of individuals who formed their health management groups and child caretaker networks. Infants and toddlers were considered at higher risk than newborns for illness due to "evil harm" inflicted by other people and/or voodoo spirits. Implications for transcultural nursing practice include developing community outreach programs, implementing nursing interventions that combine biomedical and ethnomedical preventive health care measures, and functioning as part of the health management group. The authors wish to thank Maude Vincent, R.N., for her assistance in data gathering and analysis. PMID- 2264939 TI - Issues, questions, and concerns related to the nursing diagnosis cultural movement from a transcultural nursing perspective. PMID- 2264940 TI - Living in two worlds: a Lakota transcultural nursing experience. AB - Nursing is an applied discipline. Its major concern is with the improvement of nursing care. We deal, today, with the idea that improved nursing care can be given through heightened cultural sensitivity. The author relates a case study in which she was challenged to provide the roles of nurse-collaborator and nurse educator to a Native American family in a reservation setting, in South Dakota. The rewards proved beyond expectation. PMID- 2264941 TI - Cultural care of older Greek Canadian widows within Leininger's theory of culture care. AB - Cultural care themes were abstracted from a large scale study of older Greek Canadian widows conceptualized within Leininger's theory of Cultural Care Diversity and Universality. Ethnonursing, ethnographic, and life health-care history methods were used. Data were collected using observation-participation and interviews in three Greek Canadian communities with 12 widowed key informants and 30 general informants. Enabling tools used were interview inquiry guides, Leininger's Life History Health Care Protocol, Leininger's Acculturation Rating and Profile Scale of Traditional and Non-Traditional Lifeways, and field journal recordings. Data were analyzed using Leininger's phases of analysis for qualitative data. The two major cultural care themes which were abstracted from the raw data and patterns were: (1) Cultural care for Greek Canadian widows meant responsibility for, reciprocation, concern, love, companionship, family protection, hospitality, and helping, primarily derived from their kinship, religious, and cultural beliefs, and values, and (2) Cultural care continuity diminished the spousal care void and contributed to the health of Greek Canadian widows. These findings will stimulate future nursing research related to cultural care of diverse populations and guide nursing practice to provide culturally congruent care which will assist widows to reduce their spousal care void. The author thanks Dr. Madeleine Leininger, Dr. Judith Floyd, Dr. Marjorie Isenberg, and Dr. Bernice Kaplan for their guidance in completing the large scale study on which this article is based. PMID- 2264942 TI - Cultural concepts and postpartal care. 1981. PMID- 2264943 TI - The significance of cultural concepts in nursing. 1966. PMID- 2264944 TI - An envelope-based approach for direct phase determination of macromolecular structures. AB - An initial electron density distribution for a crystal structure may be directly derived from observed diffraction data by maximizing the product of the observed and calculated Patterson functions with respect to the electron density values within an envelope. This maximization problem may be formulated as an eigenvalue equation, in which potential electron density distributions are obtained as eigendensities (eigenvectors) of a symmetric matrix. Elements of this matrix depend only on the indices and intensities of the observed reflections, and on the coordinates of grid points inside the envelope. Eigendensities are calculated for a set of small envelopes (enclosing about 20% of the molecular volume) covering a unique region of the unit cell whose points are unrelated by space group operations, origin shifts or changes in enantiomorph. On the basis of correlation coefficients between the observed and calculated values for both the Patterson function and structure-factor amplitudes, a small set of eigendensities are selected for combination into a final electron density distribution. This electron density distribution may be Fourier transformed to yield calculated structure factors. Test calculations on lysozyme indicate that phase errors of less than 60 degrees may be obtained for strong low-resolution reflections by this procedure. An extension of this approach to handle crystal structures containing non-crystallographic symmetry is described. PMID- 2264945 TI - Medicare physician payment reform: the challenges and opportunities to physiatry. An editorial board commentary. PMID- 2264946 TI - Clinically relevant designs for rehabilitation research: the idiographic model. AB - Traditional rehabilitation research involves designs emphasizing between-subject statistical evaluation and comparisons across two or more groups. The argument is made that these designs are often of limited use in clinical environments characterized by small samples and large within-group variability. The idiographic model of research design is presented as on alternative to traditional group comparison design. Idiographic, or single-subject, research emphasizes continuous monitoring of patient performance within a specified design framework. The advantages and limitations of both single-subject and group comparison designs are presented. Both designs can help establish the efficacy of rehabilitation practice and contribute to rehabilitation science. PMID- 2264947 TI - Comparison of median and posterior tibial nerve somatosensory evoked potentials in ambulatory patients with definite multiple sclerosis. AB - Somatosensory evoked potentials (SEPs) were recorded for stimulation of both median nerves and both posterior tibial nerves in control subjects and in subjects with multiple sclerosis (MS) of several years' duration, who were ambulatory and not experiencing exacerbation. Documentation of peripheral nerve conduction revealed no abnormalities in any of the subjects. Centrally, abnormal responses to median and posterior tibial nerve stimulation were found at the spinal level and/or the scalp in nearly all MS patients. Using the latency of the initial negativity of scalp SEPs, posterior tibial SEPs were abnormal significantly more often than median SEPs. Calculations suggested a significant increase in spinal conduction time. The high incidence of abnormal SEPs does not support any substantial physiological recovery in this group of MS patients. PMID- 2264948 TI - Differential reading recovery in patients with severe to moderate closed head injury. AB - A differential recovery was seen when alternate forms of a nationally standardized test of Reading Vocabulary, Literal Reading Comprehension and Inferential Reading Comprehension was administered serially to 10 consecutive closed head injury admissions to a university rehabilitation hospital. Inferential Reading Comprehension was the most impaired and had the fastest recovery rate. Subtle cognitive deficits in Inferential Reading Comprehension were detected when Reading Vocabulary was at or better than a twelfth grade level. Maximal recovery of all three reading functions occurred within 4 months after trauma, with most occurring in the first 3 months. The reading recovery pattern parallels the recovery of intelligence scores in the literature. PMID- 2264949 TI - The effects of age and peripheral vascular disease on the circulatory and mechanical response of skin to loading. AB - The skin and subcutaneous soft tissues of amputation residual limbs are required to withstand externally applied loads of greater magnitude than similar tissues of the intact lower limb. Increased age and poor circulatory status may contribute to the increased risk of tissue injury seen in this population. This study evaluates the effects of age and circulatory status as risk factors for skin injury resulting from externally applied forces. Twelve young control (YC), six elderly control (OC) and 11 subjects with peripheral vascular disease (PVD) were studied. After base-line ankle arm index (AAI) measurements, TcPO2 electrodes were applied 10 cm below the knee over the medial surface of the tibia and the muscle belly of tibialis anterior. TcPO2 measurements and tissue displacements were obtained under the influence of incremented, normally oriented, external loads. The sensitivity of the tissues to applied loads was determined by calculating the load at which the TcPO2 reached zero. The stiffness of the tissues (displacement/load) was calculated under high (greater than 40 mm Hg) and low (less than 20 mm Hg) loading conditions. No difference was noted in tissue sensitivity to applied loads between the OC and YC populations. The TcPO2 decreased to zero in the PVD population at significantly lower applied loads than both the OC and YC populations. The tissue stiffness of the PVD and the OC populations over bone was greater than the YC population, but no significant differences were noted between the PVD and the OC populations. In summary, increased age does not result in a greater tissue sensitivity to externally applied loads, in spite of the demonstrated increased tissue stiffness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264950 TI - Motor-evoked potentials reflect spinal cord function in post-traumatic syringomyelia. AB - The purpose of this study was to examine electrophysiologic abnormalities, including motor-evoked potentials, in a patient with post-traumatic syringomyelia before and after syringopleural shunting. A patient with C5 quadriplegia presented with pain, ascending sensory loss, and new weakness in the left upper extremity two yr after spinal cord injury. MRI revealed a syrinx extending from C2 to T12. We measured central motor conduction times (CMCTs) to the biceps, median F-wave latencies, needle electromyography and motor nerve conduction studies. Six days before surgery, CMCTs were 9.0 ms on the left and 7.8 ms on the right (normal less than 8.0), median F-waves were absent on the left and needle EMG revealed evidence of denervation in the left biceps. Fifteen days after syringopleural shunting at the T7 level, CMCTs had dropped to 6.9 ms on the left and 4.6 ms on the right; the left median F-wave reappeared with a normal latency. Repeat MRI revealed the syrinx to be smaller in diameter. These results suggest that CMCTs measured from magnetic stimulation of the motor cortex may be useful in the diagnosis of post-traumatic syringomyelia, as well as for following such patients postoperatively. PMID- 2264951 TI - Spasticity in spinal cord injured persons: quantitative effects of baclofen and placebo treatments. AB - Spasticity commonly occurs after a spinal cord injury and is characterized by increased resistance to passive movement of peripheral joints. This study examined the effect of an antispasticity medication on stiffness from the myotatic reflex response generated by passive sinusoidal ankle motion. A repeated measures, multiple base-line, single-subject, double-blind design was employed. The independent variable was spasticity medication treatment, where the levels were 40 mg/day and 80 mg/day of baclofen v placebo treatment. Viscous and elastic stiffness measurements were taken at the ankle joint during a placebo base-line phase and during treatment with baclofen for five adult males with traumatic spinal cord injuries. Ankle sinusoidal oscillation frequencies were from 3 to 12 Hz during test sessions. Mean viscous and elastic stiffness scores for all frequencies were calculated for each phase of the study. Randomization tests of mean changes in stiffness measurements between each treatment phase of the study failed to provide any convincing evidence of a significant treatment effect for reduction of spasticity in the traumatic spinal cord injured subjects studied. Further testing is needed to exclude potential confounding factors before this conclusion can be confirmed. The results suggest that baclofen is not a universal treatment of choice for all individuals with spasticity resulting from traumatic spinal cord injury. PMID- 2264952 TI - Research in physical medicine and rehabilitation. XI. Research training: setting the stage for lifelong learning. AB - This is the summary article in our research series. We have attempted to provide useful information for persons at all levels of research training, from the student to the clinician with a collaborative but not active role, to the new clinical researcher, to the experienced faculty member. But there is much more to be learned than can be presented in a short series of articles. From this series, you should be able to make a reasoned choice about what role in research you would like to take, and seek to maintain or upgrade your research skills to accomplish that. The previous articles, exercises and references presented will guide you in independent study. The focus of this article is to help you choose an environment in which you can continue to learn and develop. Although the "ideal" place as described here may never exist, no institution is totally devoid of research possibilities and you can use this article to help seek or develop local resources you may not have considered. By extracting questions and clues from people around you, you stimulate them to "think research" even if a formal program is absent; at the least, you can ally yourself with a nearby institution which has researchers in other clinical specialties or areas of basic science. Each organization is obviously different, having different strengths and resources. It is up to each chairperson to decide what proportion of limited resources should be invested in research. Once this decision is made, it is the initiative of the individual faculty members that will make a productive department. PMID- 2264953 TI - Rehabilitation of patients with human immunodeficiency virus (HIV). Patient confidentiality v treatment team right to know. PMID- 2264955 TI - Spinal cord injury. PMID- 2264954 TI - Anatomical study of the needle-electrode insertion into tibialis posterior. PMID- 2264956 TI - Emergency management of spinal cord injuries. AB - The emergency nurse must anticipate the presence of SCIs. Spinal cord-injured patients should be considered acutely ill and assessed in a comprehensive manner. The occurrence of a SCI may mask symptoms of underlying pathologic conditions that, if left untreated, are life-threatening. The emergency nurse is in a pivotal role, whether functioning in a prehospital setting or in the ED, to intervene rapidly. PMID- 2264957 TI - Neurologic considerations in the critical care phase. AB - The critical care phase of spinal cord injury includes basic physiologic support of the cardiovascular and respiratory systems, as well as attempts to combat secondary effects of the injury. Critical care management is also aimed at preventing the complications of this devastating injury. Research has turned its focus to improving the neurologic outcome for these patients and the use of new pharmacologic agents will hopefully meet this goal in the near future. The critical care nurse is the most important component in meeting the goals of critical care management. Continued assessment and monitoring of the patient and appropriate nursing interventions are critical to allow the patient the best chance for optimal recovery. PMID- 2264958 TI - Cardiovascular considerations in the critical care phase. AB - Spinal shock results in impaired cardiovascular reflexes of those persons with spinal cord injury above T6. This population can be at high risk for cardiovascular instability. Sympathetic pathways are interrupted and the result is uninhibited vagal tone and vascular atony. The spinal shock victim presents with hypotension, hypothermia, and bradycardia. Hypovolemia, hypoxia, and further temperature decreases can precipitate instability. Overhydration can lead to pulmonary edema and extended injury. The goal of therapy is to optimize perfusion with positioning, careful fluid replacement, and pharmacologic agents as needed. Cardiac rhythm disturbances are common and can be potentiated by hypoxia, endotracheal suctioning, hypothermia, and position changes. The goal of treatment is to avoid the offending event and to pretreat anticipated bradydysrhythmias with atropine. Close monitoring of cardiac and respiratory status is a minimum requirement for such patients. Within the high risk group exists a subgroup who demonstrate a high degree of cardiovascular instability. This group has a high mortality rate. Identification of patients who may require prolonged monitoring or more aggressive therapies may assist in eventual positive outcomes. PMID- 2264959 TI - Pulmonary considerations in the critical care phase. AB - Spinal cord injuries create alterations in ventilatory mechanics that range from complete ventilator dependence in high cervical injuries to the need for an assisted cough to clear secretions in low thoracic injuries. The initial nursing assessment should include the degree of respiratory muscle impairment, the effectiveness of the patient's inspiratory efforts, and the ability to cough. Once the mechanisms responsible for respiratory difficulty have been determined, nursing interventions can be planned to compensate for impaired function. This may involve assisted coughing, frequent chest physiotherapy and suctioning, monitoring vital capacity and ABGs, and use of kinetic beds. Perhaps the greatest challenge for both the nurse and the patient is weaning from mechanical ventilation. Weaning requires a coordinated plan, based on trust between patient and nurse, in order to achieve maximum independence from ventilatory support. PMID- 2264960 TI - Nutrition in acute spinal cord injury. AB - Nutrition in acute spinal cord injury is complicated. Not every aspect of nutrition as it relates to the acutely injured spinal cord patient is known. The stress response to injury, fever, infection, sepsis, and surgery alter nutritional needs, as does the spinal cord injury itself. The sequelae of spinal cord injury, including denervation atrophy and paralysis, glucose intolerance, skin and wound breakdown, poikilothermy, anemia, respiratory paralysis, pneumonia, paralytic ileus, gastrointestinal ulcers and hemorrhage, neurogenic bowel and bladder, and depression, all affect the nutritional needs of the patient. Orthopedic appliances, pharmacologic agents, and other injuries can also alter nutritional requirements. Nutritional assessment in acute spinal cord injury is also complex. It should include medical and diet history, physical examination, intake and output measurements, prediction of energy expenditure and protein requirements, or--even better--measurements of energy expenditure with indirect methodology, using the metabolic cart or pulmonary artery catheter. Application of computerized tomography and radioisotope studies may prove valuable in the future. Finally, the direct relationship between nutrition and physiologic alterations of acute spinal cord injury necessitates that the critical care nurse incorporate nutrition-focused thinking into many aspects of the acute spinal cord--injured patient's care. PMID- 2264961 TI - Elimination concerns with acute spinal cord trauma. Assessment and nursing interventions. AB - Elimination for the spinal cord-injured patient presents a challenge to nurses in both the acute and rehabilitation phases. The most frequent GI and urinary complications associated with spinal shock are gastric dilatation and paralytic ileus, stress ulcers, metabolic disturbances, and neurogenic bowel and bladder. Associated clinical findings are often altered or absent from the lack of sensory, motor, and reflex functions. Nonspecific signs and symptoms such as anorexia, nausea, and vomiting, create the need for complex differential diagnosis. Critical care nurses have a vital role in this diagnostic process by monitoring and reporting significant changes in assessment and laboratory findings. In addition, care measures are directed at preventing complications or supporting the patient's current condition. These interventions include gastric decompression, gastric pH monitoring, administration of antacids, nutritional support, and early bowel and bladder management. PMID- 2264962 TI - Early mobilization in acute spinal cord injury. A collaborative approach. AB - It is apparent that if comprehensive care of the spinal cord-injured patient is to be provided, there must be a team effort. The members of the team can use the strategies described to develop a good working relationship that will lead to optimum care for the patient. Using the rehabilitation team model may promote the process of team development and interaction. This leads to appreciation of each team member's contributions and demonstrates how team members compliment each other in the treatment of the SCI patient. PMID- 2264963 TI - Individual and family responses to acute spinal cord injury. AB - This article discusses individual and family responses to acute spinal cord injury from both research and clinical practice perspectives. Investigations concerning individuals' physical reactions, psychologic adjustment, and occurrence of depression are reviewed. Research studies on the demographics of and adjustment and role changes within families of patients with spinal cord injuries are critiqued. Suggestions and guidance emerging from these studies are discussed and applied to clinical practice. Clinical practice perspectives are further developed in a discussion of the needs and resources of these patients and their families. Grief, powerlessness, positive manipulation, and quality-of life issues are also explored. PMID- 2264964 TI - Pediatric spinal cord injury. AB - Although the incidence of spinal cord injury in childhood is lower than in adults, the impact is significant when the number of years with resulting severe limitations are considered. Prevention is the key to spinal cord management in all age groups, but takes on a stronger, more emphasized sense of urgency with children. If methods of prevention fail, successful early management of a child with spinal cord injury is the best hope for a future filled with accomplishments. PMID- 2264965 TI - Ethics. PMID- 2264966 TI - Ethical dilemmas. AB - Dilemma is the name we reserve for some of the hardest cases and issues in ethics. Ethical dilemmas arise from fundamental conflicts among ethical beliefs, duties, principles, and theories. This article discusses some of the morally disturbing dilemmas in nursing practice. PMID- 2264967 TI - Reflections on ethics consultation in critical care settings. PMID- 2264968 TI - Enhancing your ethical reasoning. AB - There is nothing a nurse does more frequently than make decisions, and in intensive care most of these decisions have ethical ramifications. Critical care nurses and other health care professionals must be more effectively prepared to resolve the complex ethical problems that are a natural by-product of health care in the 1990s. Each of us has an obligation as a patient advocate to use a systematic decision-making process, not just an emotive one, when faced with difficult ethical dilemmas. This article presents a decision-making process that is based on the steps of the nursing process, the theories of deontology and utilitarianism, and the strengths in the steps of the valuing process. A difficult case is shared at the end of the article that challenges the reader to examine his or her decision-making capabilities from a systematic and ethical perspective. PMID- 2264969 TI - Culture, mortality, and ethics. Twirling the spindle. AB - A clear account of the relationship of mortality to culture can improve understanding of ethical issues in health care. Ethics as an area of scholarly study can also be distinguished from morality and culture. This article clarifies the relationships among institutional culture, mortality, and ethics scholarship. Nurses who understand that mortality is part of culture can engage in a variety of activities to improve the moral qualities of institutional culture in hospital settings. PMID- 2264970 TI - Competence and the nurse-patient relationship. AB - Patient competence is a prerequisite to fulfilling the primary ethical principle of patient autonomy or self-determination. This article defines the legal designation of incompetence and describes the components of the assessment of a patient's decision-making capacity. These assessments occur within the context of relationships, the most influential of which is that between the nurse and patient. Attention to the nurse-patient relationship promotes patient autonomy, patient advocacy, and decision making based upon the patient's values--which is, ultimately, ethical health care. PMID- 2264971 TI - Informed consent and the elderly. An ethical challenge for critical care nursing. AB - Nursing ethics was long reticent about ethical challenges that elderly patients pose for critical care nursing. One of these, the legal doctrine of informed consent, has important implications for critical care nursing ethics. Deriving from the principle of respect for persons and intended to preserve their autonomy, informed consent represents both a duty and an ideal for care givers to implement in the process of ethical decision making. All too often the ideal is lost, however, and the doctrine reduced to a sterile and bureaucratic procedure. When elderly patients are unable to give an adequately informed consent, advance directives can enable them to express their wishes by prior choosing. If they become cognitively impaired, however, it is much more difficult to determine what, if any, preferences such a patient might express if able to do so. Medical empowerment of the elderly, a laudable social goal, can be as contradictory as informed consent itself and many elderly patients may opt out of their own decision making. The resultant moral distress of such a complex process is still another ethical challenge that faces the critical care nurse. Because nursing holds a position of moral centrality among the health care professions, critical care nurses cannot avoid the prospect that issues like those identified in this article will continue to challenge and confront them in the coming decade. By turning to colleagues in nursing as well as other professions, nurses can best strengthen and consolidate their vital role as mediators of meaning and morality in life-and-death situations. PMID- 2264972 TI - Does the DNR patient belong in the ICU? AB - A small but significant percentage of ICU patients are designated DNR at some time during their ICU stay. DNR patients in the ICU are more ill, use more resources (including nursing care) and have a higher mortality rate than non-DNR patients. In an age of a critical care nursing shortage, spiraling health costs, and an emphasis on the just allocation and use of scarce resources, the question whether DNR patients should be excluded from the ICU is appropriately raised. After examination, a model policy to exclude DNR patients from the ICU was rejected because a policy excluding DNR patients from the ICU would have adverse effects on patient autonomy, beneficence, the nurse-patient relationship and fidelity, and the practice of writing DNR orders. Furthermore, such a policy would not resolve triage problems. DNR patients can appropriately be given curative or palliative treatment in an ICU when their treatment goals are reasonable and the treatment can only be given in the ICU. Conversely, DNR patients do not belong in the ICU when their treatment goals are inappropriate or when their treatment could be received on another unit. "Appropriate" and "inappropriate" treatment was not thoroughly examined except to define them in relation to Young's "point Z," the theoretical point on a life-death continuum at which one stops prolonging life and instead prolongs death. In this authors' opinion, beyond point Z, only palliative treatment is justified in the ICU. DNR patients beyond point Z should not receive curative treatments in the ICU. Many DNR patients fitting this description remain in ICUs, however, perhaps because of physician reluctance to withdraw or withhold life-sustaining treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264973 TI - Balancing the benefits and burdens of ECMO. The nurse's role. AB - Technologic innovations such as extracorporeal membrane oxygenation generate a myriad of ethical concerns that complicate clinical treatment decisions. Nurses must engage in deliberate actions to raise the issues of balancing the benefits and burdens of the technology, access to therapy, informed consent, and allocation of scarce resources, in order to provide ECMO services in an ethically sound manner. Consumers and providers of ECMO services must continue to examine and debate these issues in a reasoned, deliberate fashion and construct the necessary procedural safeguards that will ensure beneficent and just delivery of these services. PMID- 2264975 TI - Intensive nursing care. The ministry of presence. AB - The nurse's presence offers meaningful support to people in critical care situations. Because crisis and suffering dispirit a person, there is an increased sense of vulnerability, isolation, and alienation, as well as a decreased sense of relationship and being heard in an environment that is already overwhelming, often associated with pain, frightening, and unfamiliar. The nurse's presence can lessen these negative effects of suffering as one comes alongside and enters that suffering by listening and being available in a way that involves self-giving. In this way, the nurse is fully attentive with all of self, as opposed to seeming to be. The idea of being present may be threatening to a nurse because it requires exposing one's vulnerability in order to come alongside one who is already very ragged and exposed. The silence also may be intimidating as the nurse chooses to wait with a person who is in turmoil and wrestling emotionally, mentally, physically, or spiritually. Another challenge for the nurse is confronting traditional attitudes about what it means to "be professional" and "therapeutic." The experience of presence is an awesome privilege humbly received as one realizes the personal cost to the one who chooses to share inner wrestling and brokenness. Presence occurs only with the permission or invitation of the one suffering and only when the nurse is willing to accept the invitation and also be that vulnerable. Because suffering often triggers spiritual wrestling in addition to emotional, mental, and physical pain, the nurse may be invited to come alongside a person in a role that interfaces with that of the chaplaincy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264974 TI - Critical care nursing. Expanding roles and responsibilities within the community. AB - The health care system in the United States is undergoing many changes, including the return of chronically dependent individuals who are medically fragile to the community's homes and schools. Community-based health care, when compared with hospital care, is more cost effective and is the consumer's preference. The supportive technology to perform skilled therapies is available and recent legislation, although not adequate, provides support. Not only is the community becoming an arena for the provision of more complex care, it is also becoming an arena for addressing ethical issues. The nursing profession is challenged to prepare skilled nurses for the greater independence that is required in community based practice. Nurses need to become more aware of the authority inherent in their professional role in order to most effectively address and resolve the more complex and often intensive care needs of their clients who are medically fragile and being cared for in the community and to guide their families in the resolution of related ethical dilemmas. PMID- 2264976 TI - Ethical components of caring. AB - The meanings of caring that emerge from the ethics literature are professional value; personal value; understanding humankind's existence; understanding meaning of values, choices, and priority systems; moral decision making; dignity; worth; healing powers within; being treated as a person; and partners in treatment. These meanings of caring are incorporated into the practice realm of critical care nurses. Clients in the critical care units demand a nurse who will treat them with respect, understanding, dignity, worth, partnership; provide choices; understand their values; guide them in moral decision making; and empower their healing capacities. As technology continues to explode, more and more ethical dilemmas will evolve and the critical care nurse will need to bridge the advancing technology with human caring. Then her expert nursing care will make the empowering difference in the client's care. PMID- 2264977 TI - Contemporary bioethical issues in critical care. AB - The critical care nurse confronts ethical dilemmas in practice on a regular basis. Problems concerning treatment issues, allocation of resources, and collegial disputes are common. Knowledge of available resources can assist the nurse in dealing with these dilemmas. PMID- 2264979 TI - Myoclonus, seizures, and paratonia in Alzheimer disease. AB - Twenty-eight patients with the clinical diagnosis of probable Alzheimer disease (AD) were followed longitudinally until death. The presence of myoclonus, seizures, and paratonia was monitored as part of this process. At autopsy, 22 of the patients met pathologic criteria for AD and 6 had other degenerative neurologic diseases. Myoclonus was present in 55% of the AD patients and none of the non-AD patients. Seizures were present in 64% of the AD patients, and only 17% of the non-AD patients. Paratonia was found frequently in all patient groups. In most patients, symptoms developed late in the course of their illness. The incidence of myoclonus, seizures, and paratonia in our patients was higher than in most previous studies. The reasons for this finding are discussed. PMID- 2264978 TI - Clinical drug trials in Alzheimer disease. What are some of the issues? AB - Clinical drug trials in Alzheimer disease are underway in many locations throughout the world. That experience has uncovered a number of unique difficulties. In response, members of the Alzheimer's Association Medical and Scientific Advisory Board organized meetings with experts from the government, academia, private practice and the pharmaceutical industry. The issues are presented here along with some suggestions to facilitate planning and to avoid problems in future drug trials. PMID- 2264981 TI - Irreversible loss of cognition? A caveat. PMID- 2264980 TI - Oral physostigmine as treatment for dementia of the Alzheimer type: a long-term outpatient trial. AB - Six patients with dementia of the Alzheimer type (DAT), treated with oral physostigmine and followed from 9 to 27 months (mean +/- SD, 17.8 +/- 7.3 months), were matched for sex, age, initial degree of dementia, and length of follow-up with six control patients who did not receive oral physostigmine. The small sample size precluded drawing definite conclusions about overall efficacy; however, three in the physostigmine group did not deteriorate during the course of follow-up while all of the controls deteriorated although the difference was nonsignificant. The data generated in these patients provides evidence of the safety of long-term trials of oral physostigmine. The possible role of cholinesterase inhibition in retarding the progression of DAT is discussed. PMID- 2264982 TI - Postinflammatory scarring of cardiac valves of rheumatic and nonrheumatic etiology. AB - In rheumatic heart disease, cardiac valves often display only a nonspecific postinflammatory scarring, without specific features, such as the rheumatic granuloma. Fifty-five native valves excised from 47 patients, exhibiting postinflammatory scarring, were studied. Patients were subdivided into three groups according to their case histories: patients with both streptococcal infection and rheumatic fever (group I), with streptococdal infection without noncardiac major manifestations of rheumatic fever (group II), and without either of these features (group III). Pathological examination alone was unable to differentiate among the three groups, all the valves showing the same general pathological features. Differences in terms of sex, age, and valvular involvement were detected among group III and the others, whereas patients belonging to the first two groups did not differ significantly. These results suggest that diagnostic criteria for rheumatic fever are too restrictive and that a postinflammatory valvular scarring of nonrheumatic etiology does exist. PMID- 2264983 TI - Absence of one atrioventricular connection associated with straddling atrioventricular valve: distinction of a solitary from a common valve and further considerations on the diagnosis of ventricular topology. AB - Hearts with absence of the right atrioventricular connection (tricuspid atresia) are rarely associated with straddling of the left atrioventricular valve. We describe two hearts in which the left atrium is connected mostly to a dominant left ventricle but, in part, to a rudimentary right ventricle. In these particular hearts, this arrangement caused major problems in determining ventricular topology. This feature, the so-called handedness of the ventricular mass, is determined in hearts with two complete ventricles by attempting to place the palm of one's hand on the right ventricular septal surface with the thumb in the inlet and the fingers pointing to the outlet. The problems in these two cases were produced because the rudimentary right ventricle had only part of an inlet component. The discerned pattern of topology was different in the two cases, being left hand in one and right hand in the other. These cases emphasize, first, the need to distinguish between ventricular topology and the atrioventricular connection and, second, between a solitary and a common atrioventricular valve when the valvar tension apparatus is straddling. PMID- 2264984 TI - The site of origin of nonconfluent pulmonary arteries from a common arterial trunk or from the ascending aorta: its morphological significance. AB - There are three possible embryological derivatives for nonconfluent pulmonary arteries which arise from a common arterial trunk or from the ascending aorta. We considered the feasibility of identifying these derivatives on the basis of the site of origin. We examined 15 specimens, in which both pulmonary arteries arose by separate orifices from a common arterial trunk (persistent truncus arteriosus), and 3 specimens, in which one pulmonary artery arose from the ascending aorta, the other being connected to the morphologically right ventricle (hemitruncus). Measurements were made for both the upper and lower margins of the orifices of the pulmonary arteries and then expressed as a percentage of the length of the ascending common trunk or aorta. The position of origin ranged from 39 to 100% for the upper margin and from 17 to 90% for the lower margin, without significant difference between left and right arteries. Since the range varied so widely, we contend that it is not possible to make a morphological identification of the pulmonary artery under consideration simply on the basis of the location of the site of origin. PMID- 2264985 TI - Characterization of inflammatory cells in a patient with chronic periaortitis. AB - During repair of an inflammatory abdominal aortic aneurysm, fresh samples of the aneurysm wall were obtained. Histology confirmed the diagnosis of chronic periaortitis,- advanced atherosclerosis with medial attenuation, and periaortic inflammation. Monoclonal antibodies were used to identify the cells of the inflammatory infiltrate. The majority of the adventitial lymphocytes were B cells. No B cells were present in the atheroma. The majority of mature plasma cells contained IgG with a few plasma cells containing IgM. T cells, predominantly T helper cells, were found in the atheroma and adventitia. Positive DR staining was shown by the majority of lymphocytes, by macrophage-like cells in germinal centers of lymphoid follicles in the adventitia, by some vascular endothelial cells, and by some smooth muscle cells. The implications of these findings are discussed. PMID- 2264986 TI - Effect of carnitine on size limitation of experimental myocardial infarct. AB - To elucidate 1-carnitine chloride effects ischemic myocardium for the possibility of a salvage of risk zone around necrosis in myocardial infarcts of dogs, a quantitative evaluation of the extent of myocardial infarcts was done by size detection with use of monastral blue and tissue dehydrogenase histochemistry at 20 hours after coronary ligation. The results show that the ratio of unsalvaged infarct zone to occluded coronary bed is 85.3 +/- 2.9% in the control group, while it is 53.2 +/- 3.6% in the 1-carnitine administered (1 C) group. The difference between these ratios is statistically significant (p less than 0.01). The results also indicate significantly lower serum CPK concentration. Therefore, carnitine may play a role in preventing a size extention of infarcts through improving an altered lipid metabolism, particularly a fatty acid metabolism, of myocardial cells in the risk zone. PMID- 2264988 TI - Shifts in calcium in ischemic and reperfused rat hearts: a cytochemical and morphometric study of the effects of diltiazem. AB - Effects of diltiazem upon mitochondrial ultrastructure and distribution of calcium were studied following ischemia (27 minutes) and reperfusion (30 minutes). Hearts receiving no drug recovered low contractile function, while mitochondria nearly doubled in cross-sectional area (0.98 vs 0.56 micron 2) and were structurally damaged (1.88 vs 0.17 score). Mitochondria contained fine calcium deposits (0.029-micron diam) in mildly damaged cells, larger deposits in moderately damaged cells, and a large deposit (0.17-0.29-micron diam) in severely injured cells. Glycocalyx Ca2+ stain, observed in nonischemic hearts, was reduced in moderately and severely damaged cells. Increased mitochondrial Ca2+ may be associated with loss of glycocalyx Ca2+. Diltiazem (7.5 microns), added before ischemia, improved recovery of contractile function and prevented mitochondrial swelling, structural grade change, and increase in mitochondrial Ca2+. Reduction in mitochondrial Ca2+ stain by diltiazem was associated with the maintenance of normal glycocalyx Ca2+. PMID- 2264987 TI - Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium. AB - To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/ 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion. PMID- 2264990 TI - Quadricuspid aortic valves. PMID- 2264989 TI - Primary liposarcoma of the heart. AB - We report the eleventh illustrated case of primary liposarcoma of the heart in a 28-year-old man. The tumor arose from the mitral valve and the left ventricle and was revealed by a solitary brain metastasis 1 year before. The primary tumor and the metastasis were surgically removed. The cardiac and brain neoplasms were myxoid liposarcoma, as confirmed by histochemical, immunohistochemical, and ultrastructural studies. Although review of the literature points out the poor survival of patients with malignant liposarcoma of the heart, no recurrence or metastasis was observed after a 6-month follow-up. PMID- 2264991 TI - Culturing two- to eight-cell caprine embryos using domestic chicken eggs. AB - Early-stage caprine embryos were placed in the chick embryo amnion to determine if this culture method would support the development of embryos from a farm animal species. Following superovulation and natural mating, two- to eight-cell embryos were surgically collected from crossbred donor goats. Embryos were allotted to in vitro culture treatments across two different experiments (EXP). In EXP-I, embryos allotted to Treatment A (control) were cultured in Ham's F-10 with 10% fetal calf serum and 1% antibiotic-antimycotic (HF-10). Embryos in Treatment B were placed on a bovine fetal uterine fibroblast monolayer in HF-10, embryos allotted to Treatment C were agarose embedded and injected into the amniotic cavity of a day-4 chick embryo and those placed in Treatment D were co cultured in HF-10 with day-15 caprine trophoblastic vesicles. In EXP II Treatments A, B, and C were the same; however Treatment D was omitted. EXP-I and EXP-II also differed in that chick embryo co-culture was for 72 hr in EXP-I but was extended to 96 hours in EXP-II. Additionally, the monolayer co-culture was limited to 96 hr in EXP-II; whereas, embryos in EXP-I remained on monolayer culture for 96 hr plus an additional 72 hr for subsequent embryo evaluation. Results indicate that the amniotic cavity of the developing chick embryo enhanced the development of two- to eight-cell caprine embryos through to hatching blastocysts when compared with that of the control medium alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264992 TI - Production of chimaeric bovine embryos and calves by aggregation of inner cell masses with morulae. AB - Bovine inner cell masses (ICMs) were isolated by immunosurgery at day 8 or 10, or by dissection at day 14, and combined with day-5.5 morulae. Aggregation was obtained between 89%, 62%, and 0% of the day-5:day-8, day-5:day-10, day-5:day-14 composites, respectively. Chromosome analysis of composites, respectively. Chromosome analysis of composites potentially carrying the 1/29 translocation as a chromosome marker and temporarily transferred to the bovine uterus for 8 days showed that chimaeric day-14 embryos can be obtained from day-5:day-8 aggregation. The definitive transfer of eight day-5:day-8 and 11 day-5:day-10 composites resulted in the birth of six and four calves, respectively; five of the six, but none of the four, were chimaeric. The five chimaeras showed mostly the ICM phenotype. The morphological differences between ICMs at different stages of development were examined by electron microscopy and related to the success of the aggregation technique. It is concluded that bovine embryonic cells can regulate for at least 3 days difference in development but not 5 days even though aggregation is still possible. PMID- 2264993 TI - Characterization and inhibitor sensitivity of human sperm phospholipase A2: evidence against pivotal involvement of phospholipase A2 in the acrosome reaction. AB - The kinetic properties and inhibitor sensitivity of human sperm phospholipase A2 (PLA2; EC 3.1.1.4) were studied. Phospholipase activity was isolated from human spermatozoa by acid extraction. Hydrolysis of dipalmitoyl phosphatidylcholine was specific to the sn-2 position. Activity was sensitive to product inhibition (60% inhibition by 0.1 mM lysophosphatidylcholine). The effects of Ca2+ and sodium deoxycholate on enzyme activity were biphasic; maximal activities were observed at 0.5 mM concentration of each agent. PLA2 was stimulated (135%) by 3% dimethylsulfoxide and was inhibited by elevated ionic strength (approximately 70% inhibition with either 0.2 M NaCl or 0.2 M KCl). Two molecular forms of PLA2 were kinetically distinguishable, one with an apparent Michaelis constant and maximal reaction velocity of 3.0 microM and 0.64 mlU/mg protein and the other with respective constants of 630 microM and 32.0 mlU/mg protein. Both forms of the enzyme were Ca2+ dependent and heat stable; however, the low-Km activity was less resistant to 60 degrees C preincubation at pH 7.5 (28% inactivation of low-Km activity after 45 min, as compared to no effect on high-Km activity). Quinacrine was a noncompetitive PLA2 inhibitor with Kis for low- and high-Km activities of 0.42 mM and 0.49 mM, respectively. Trifluoperazine (calmodulin antagonist) inhibited the high-Km activity noncompetitively (Ki = 87 microM) and the low-Km activity by a mechanism consistent with the removal of a nonessential activator. Dissociation and rate constants for inactivation of low- and high-Km activities by p-bromophenacyl bromide were 0.28 mM and 0.032 min-1, and 0.73 mM and 0.066 min-1, respectively. PLA2 was inhibited by p-nitrophenyl-p'-guanidinobenzoate, at higher concentrations (10(-4)-10(-3) M) than required to inhibit trypsinlike proteinases; p-aminobenzamidine, another potent trypsin/acrosin inhibitor, stimulated (approximately 40%) PLA2 at concentrations from 2-5 mM but inhibited PLA2 (40-50%) at a concentration of 10 mM. MnCl2 (5mM) inhibited low- and high-Km PLA2 activities by 77% and 76%, respectively. Quinacrine (0.4 mM), trifluoperazine (20 microM), p-bromophenacyl bromide (20 microM), and MnCl2 (5 mM) were tested as inhibitors of the ionophore A23187-induced human acrosome reaction. Inhibition was noted only with quinacrine (32%) and MnCl2 (93%). The effect of MnCl2 was restricted to an interaction with A23187, rather than with PLA2; p-Bromophenacyl bromide inhibited (P less than 0.05) PLA2 (29%) when added to intact spermatozoa but had no effect on the acrosome reaction. PLA2 inhibition was poorly correlated with the acrosome reaction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2264994 TI - Prediction of human sperm penetrating ability using computerized motion parameters. AB - The sperm penetration assay (SPA) is used to assess male fertilizing potential but it is tedious and costly. Computer analysis could replace the need for the SPA in some cases, if computerized sperm motility parameters are highly predictive of SPA performance. The objective of this study was to determine whether computerized motility parameters from fresh semen samples could be used to predict SPA performance. Computer automated semen analysis (CASA; CellSoft, Cryo Resources) was used to quantitate sperm concentration (CONC), percent motility (MOT), curvilinear velocity (VEL), linearity of swimming trajectory (LIN), mean amplitude of lateral head displacement (ALH), and beat/cross frequency (B/CF). The SPA was performed using either Biggers, Whitten, and Whittingham's medium (BWW) or TEST-yolk buffer (TYB). Patients were divided into three groups depending on SPA performance: group 1, BWW-treated, 0% versus greater than 0% penetration; group 2, TYB-treated, 0% versus greater than 0% penetration; and group 3, TYB-treated, less than 20% versus less than or equal to 20% penetration. SPA performance was highly correlated with CONC, MOT, VEL, and B/CF. CONC, MOT, VEL, and B/CF were significantly higher for patients who penetrated in the SPA than for those who failed to penetrate. Discriminant function analysis (DFA) successfully classified 76% of all patients treated with TYB (group 2) who penetrated and 86% of nonpenetrators based on their computerized motility parameters. For group 2 DFA predicted that 93 men would penetrate in the SPA with TYB. Of these, 90 (97%) successfully penetrated at least one egg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264995 TI - Zona drilling enhances fertilization by mouse caput epididymal sperm. AB - Spermatozoa from the caput epididymis are known to be much less capable of fertilization when compared to sperm from more distal segments of the epididymis. The purpose of this study was to determine if two micromanipulative techniques, zona drilling (ZD) and a modification of partial zona dissection (PZD), could be used to enhance fertilization with caput epididymal sperm. A mouse in vitro fertilization model was used. Inseminating oocytes with 500-1,000 sperm/oocyte from the cauda epididymis as a control resulted in fertilization of 98 of 300 (32.6%) oocytes. Of those fertilized, 47 developed to the blastocyst stage (47.9%). Caput sperm fertilized 13 of 116 (11.2%) nonmanipulated oocytes. Only 1 of 13 developed into a blastocyst, while with oocyte ZD, caput sperm fertilized 24 of 144 (16.7%) oocytes, 50% of those fertilized developing to blastocyst (P = 0.0129). When modified PZD was performed on oocytes, only one of 23 was fertilized, with no blastocyst development. These results indicate that acid Tyrode ZD enhances both fertilization and early embryonal development when caput epididymal sperm are used for insemination. These mouse studies suggest that ZD or other micromanipulation techniques may prove clinically useful in men with proximal epididymal obstruction where only caput sperm are available. PMID- 2264996 TI - Asynchrony between pronuclear development and protein synthetic changes in zygotes of the mouse derived from oocytes aged postovulation in vivo and fertilized in vivo. AB - The pattern of proteins synthesized by one-cell embryos derived from unaged oocytes and oocytes aged postovulation in vivo was analyzed by means of 35S methionine labeling and gel electrophoresis. The oocytes were obtained after ovulation induction by an injection of luteinizing hormone-releasing hormone (LHRH) at proestrus or after a superovulation procedure. The analysis was performed in unfertilized aged and unaged secondary oocytes and in zygotes derived from them. The patterns of proteins synthesized by secondary oocytes from all experimental groups were very similar: The oocytes showed a predominant synthesis of 35 kDa proteins. Zygotes from aged as well as unaged LHRH-induced oocytes also showed a predominant synthesis of one group of polypeptides with a relative molecular weight of about 35 kDa. The proteins of the 35 kDa protein complex migrated in an upper (u), middle (m), or lower (l) band in 10% polyacrylamide sodium dodecyl sulfate (SDS) gels. The u- and m-band 35 kDa proteins were shown to be synthesized by secondary oocytes. Early pronuclear zygotes from unaged LHRH-induced oocytes synthesized u- and m- but no l-band 35 kDa proteins. In contrast, part (38%, n = 47) of the early pronuclear zygotes from aged LHRH-induced oocytes did synthesize the l-band 35 kDa proteins. Late pronuclear zygotes (LPZ) from aged as well as unaged oocytes synthesized predominantly the l-band 35 kDa proteins. However, although only 5.8% (n = 51) of LPZ from unaged oocytes synthesize m- and l-band 35 kDa proteins, these bands of proteins are present in 25% (n = 24) of the LPZ from aged oocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2264997 TI - Observations of hamster sperm-egg fusion in freeze-fracture replicas including the use of filipin as a sterol marker. AB - We have extended the observations of previous transmission electron microscopy studies of sperm-egg fusion to include those of freeze-fracture replicas showing sperm-egg interactions before, during, and following sperm head fusion with the egg membrane. Hamster eggs were incubated with hamster sperm under polyspermic conditions and were observed after a period of 5-30 minutes. After fixation, the eggs and sperm were exposed to filipin, which binds beta-OH-sterols to form visible complexes in freeze-fracture replicas. Filipin can act as a marker for egg plasma membrane wherein it is abundant, while filipin is relatively scarce in the acrosome-reacted hamster sperm membrane, found only in the plasma membrane of the equatorial segment. The earliest sperm-egg interactions are observed between the egg microvilli and the perforatorium and the equatorial segment of the sperm, and the initial fusion between egg and sperm occurs in the vicinity of the equatorial segment. At later stages of fusion involving the postacrosomal segment, a clear line of demarcation is observed between the filipin-rich egg membrane and the filipin-poor sperm postacrosomal segment, suggesting that filipin binding lipids from the egg intercalate into the sperm membrane following membrane fusion. The anterior segment of the sperm does not fuse with the egg but is instead incorporated into a cytoplasmic vesicle derived from both sperm and egg membranes. In this latter step, filipin-sterol complexes are not found in sperm-derived membranes suggesting that there may be barriers to the movement of filipin binding lipids from the egg into these sperm membranes. PMID- 2264998 TI - Cell-cycle aspects of growth and maturation of mammalian oocytes. AB - In this review, recent data concerning growth and maturation of nonmammalian and mammalian female germ cells are compiled with regard to the increased understanding of somatic cells mitotic cycles, from yeast to human tissues. These data allow us to conclude that growing oocytes of nonvertebrates, lower vertebrates, and mammals resemble somatic cells in the G1 phase of the mitotic cycle in their metabolic and cell cycle behavior. Transcriptional and translational activity of growing oocytes and G1 somatic cells is not compatible with the activation of maturation promoting factor (MPF), with chromatin condensation or with nuclear membrane disintegration. Growing oocytes, even when they are in the dictyate stage of the first meiotic division, promptly inactivate MPF introduced into their cytoplasm by fusion or microinjection, just as do somatic interphase cells. In mammals, the LH surge induces "de novo" RNA and protein synthesis in granulosa cells. This metabolic change in granulosa cells abolishes their inhibitory activity, and meiosis in fully grown oocytes in preovulatory follicles is then resumed. Resumption of meiosis requires an activation of pre MPF molecules within oocytes. This can be achieved either without (mouse, rat, and rabbit) or with (pig, sheep, and cow) an active protein synthesis by the oocytes. The species specificity is probably dependent on the presence or absence of cyclin-like and/or mos-like molecules in fully grown oocytes. Both major events during GVBD, chromatin condensation, and nuclear envelope disintegration require protein phosphorylation. Experimentally, these two phosphorylation activities can be separated one from another. The active MPF molecules are amplified autocatalytically in amphibian and starfish oocytes. However, an increase of MPF activity in mouse and pig oocytes, similarly as in Rana pipiens and sturgeon oocytes, requires an active protein synthesis. PMID- 2264999 TI - Research for all in general practice. PMID- 2265000 TI - Compliance with medical advice. PMID- 2265001 TI - National standard setting for quality of care in general practice: attitudes of general practitioners and response to a set of standards. AB - The Nederlands Huisartsen Genootschap (NHG), the college of general practitioners in the Netherlands, has begun a national programme of standard setting for the quality of care in general practice. When the standards have been drawn up and assessed they are disseminated via the journal Huisarts en Wetenschap. In a survey, carried out among a randomized sample of 10% of all general practitioners, attitudes towards national standard setting in general and to the first set of standards (diabetes care) were studied. The response was 70% (453 doctors). A majority of the respondents said they were well informed about the national standard setting initiatives instigated by the NHG (71%) and about the content of the first standards (77%). The general practitioners had a positive attitude towards the setting of national standards for quality of care, and this was particularly true for doctors who were members of the NHG. Although a large majority of doctors said they agreed with most of the guidelines in the diabetes standards fewer respondents were actually working to the guidelines and some of the standards are certain to meet with a lot of resistance. A better knowledge of the standards and a more positive attitude to the process of national standard setting correlated with a more positive attitude to the guidelines formulated in the diabetes standards. The results could serve as a starting point for an exchange of views about standard setting in general practice in other countries. PMID- 2265002 TI - A survey of professional help sought by patients for psychosocial problems. AB - A sample of patients aged 25-75 years was drawn from one general practice. The patients were sent a postal questionnaire to ascertain whether they had had a personal or emotional problem in the last 10 years and whom they had confided in. Of the 396 respondents 281 (71%) admitted to having had such a problem. It was found that significantly more women then men had had a problem. Of these 281 individuals, 94% had confided in someone, mainly friends and relatives, 47% had consulted one or more professionals or agencies and 37% had confided in their general practitioner. Although the majority had found the contact with the agency or professional helpful, those with depression/anxiety or problems following a bereavement were less likely to feel that they had been helped. The provision of practical advice, sympathy and support were most often mentioned as being helpful. This study demonstrates the important role of the general practitioner in the management and treatment of psychosocial problems. PMID- 2265003 TI - Psychiatrists in primary care: would general practitioners welcome them? AB - During the spring of 1988 a postal questionnaire was sent to all general practitioners in one health district, enquiring about their present links with psychiatrists and asking for their views on the desirability of psychiatrists visiting their surgeries regularly. At present only a minority of general practitioners have a regular link of this kind but a substantial majority would welcome such an arrangement. The type of link most commonly desired is one in which the general practitioner shares actively in the assessment and treatment of the patient. A degree of ambivalence about the role of other mental health professionals was detected. PMID- 2265004 TI - Need for and provision of general practice in London. AB - This study examines the spatial distribution of general practice in London, taking into account both practice and population characteristics. While need for general practice is higher in inner London, some areas of outer London experience high levels of need. Inner London tends to have a greater quantity but lower quality of general practice. However, as in the case of the needs indices, this situation cannot be described as a simple inner city/outer city dichotomy. It is concluded that not all inner London areas suffer from high need and poor general practice and not all outer London areas have low need and good general practice. PMID- 2265005 TI - A model of cooperation between complementary and allopathic medicine in a primary care setting. AB - This paper describes an acupuncture and osteopathy service offered free of charge to patients at a National Health Service general practice. The background to the setting up of this service, its organization, funding, aims and philosophy, and the ethical and legal implications for the general practitioners whose patients are treated by complementary therapists are discussed. This service provides a model of cooperation between allopathic and complementary medicine in a primary care setting and could be copied elsewhere. PMID- 2265006 TI - Care of a severely handicapped person over eight years: implications for the future pattern of community care. AB - This case report describes eight years practical experience of community support for a quadriplegic woman with progressive multiple sclerosis. Key factors in avoiding institutional care were the close collaboration between general practitioner, hospital consultant and social services, and the recognition by the doctors that the social dimension was the dominant requirement for support. Other important points were the identification of one key worker from the many professionals involved, and the use of separate NHS and social service funds to employ care attendants. This funding allowed community nurses to utilize their professional skills while the care attendants solved the problems of dependency. The mechanisms of community support for the individual are discussed in the light of proposed changes in the organization of care for the disabled. PMID- 2265007 TI - A joint course for general practitioner and practice nurse trainers. AB - An experimental multidisciplinary course for prospective general practitioner and practice nurse trainers is described. Factual knowledge and attitudes were measured before and after the course and some of the changes measured emphasized the importance of multidisciplinary training. The ideas generated by the group of nurse trainers in terms of their future professional development were identified. PMID- 2265008 TI - Treatment for acute asthma in the ambulance. PMID- 2265009 TI - Advice on the appointment of psychologists and counsellors within general practices. PMID- 2265010 TI - An unusual side effect of omeprazole: case report. PMID- 2265011 TI - General practice training in musculoskeletal disorders. PMID- 2265012 TI - Leucocyte adhesion molecules. PMID- 2265013 TI - Does pertussis vaccine cause brain damage? PMID- 2265014 TI - School health services in Australia. PMID- 2265015 TI - It's time: the future of school health in Australia. AB - School medical services in Australia have a long tradition of providing community based services to school-aged children, and in some states to preschool children. Conceived as a public health measure early this century, doctors and nurses worked in schools to address the health issues of the time, which were largely to do with nutrition, hygiene, and infectious diseases. It was perceived that many children had poor access to medical care, and began school with unaddressed health problems which often had a deleterious effect on their learning. Doctors were often employed by education authorities and only transferred to health departments many years later. In some states the service was expanded subsequently to include preschool children, based on the concept that the earlier problems were detected the earlier they could be treated appropriately and the greater the benefits to the child. While social structures, community needs and paediatric morbidity patterns have changed dramatically over recent years, there is a widespread perception that in some states school medical services have not yet embraced fully the changing needs of the population of school children they are designed to serve. Hamstrung by political expediency (with decision-making driven by political rather than scientific considerations) and bureaucratic inertia, school nurses and doctors often operate in structures and systems that are urgently in need of review and reorganization. In this paper the rationale for current processes will be reviewed critically, a model of school health services focused on contemporary paediatric needs is proposed, and a set of factors which are considered essential to the development of the school health services of the future is outlined. PMID- 2265016 TI - Neonatal sepsis and infection control policies in Australia. AB - The pattern of neonatal bacterial infection, its management and the types of infection control policy were ascertained in 20 neonatal intensive care units (NICU) in Australia by questionnaire survey. Group B Streptococcus and Escherichia coli were the predominant organisms responsible for perinatally acquired infection for which the most common antibiotic combination used was Penicillin and Gentamicin. Staphylococcus epidermidis and aureus (majority Methicillin resistant) were the predominant organisms responsible for nosocomial infection for which the most common antibiotic combination used was Vancomycin and Cefotaxime. A Serratia epidemic was experienced in four NICU. Lumbar and suprapubic punctures were frequently done as part of the diagnostic workup in nosocomial infections but not with perinatally acquired infections. Haematological indices considered useful as a diagnosis aid varied between NICU and acute phase reactants were rarely relied upon for diagnosis or for monitoring treatment response. Granulocyte transfusion and intravenous immunoglobulins were infrequently used in therapy. No consensus was found on infection control policies. Eight NICU required routine gowning on entry, two restricted sibling visiting and four restricted visiting by relatives and friends. Although routine bacteriological surveillance on staff or equipment was uncommon, serial cultures were carried out in infants from the body surface in six NICU and from the endotracheal aspirate in 17 NICU. Antiseptics used with technical procedures included iodine, chlorhexidine and alcohol used singly or in combination. Skin and umbilical cord care also varied between NICU. The literature was reviewed to determine the effectiveness or otherwise of some of the existing policies in the prevention or management of neonatal infection to encourage consensus towards a more rational approach to neonatal infection in Australia. PMID- 2265017 TI - Extracorporeal membrane oxygenation (ECMO) for non-ECMO intensive care nurseries. AB - An extracorporeal membrane oxygenation (ECMO) centre has been established in the sole outborn-only level 3 nursery in Melbourne. In the absence of other guidelines, an infant may qualify for ECMO if the expected mortality, based on assessment of the severity of hypoxia, exceeds 80%. However, for a non-ECMO centre, this involves the additional hazard of transport for an already critically-ill infant. The aim of this study was to determine the predictors of at least 80% mortality in babies who might have qualified for ECMO but who were cared for in a non-ECMO level 3 nursery. Regardless of the severity or duration of hypoxia, we were unable to identify a group of infants whose mortality exceeded 80%. Since outborn infants were disproportionately over-represented amongst those who might qualify for ECMO, it would be advisable to admit preferentially those born outside the level 3 perinatal centres who might qualify for ECMO directly to the ECMO centre. For infants born within our level 3 perinatal centre, it is recommended not to transfer those who might qualify based on data from other centres until the exact role of ECMO is determined. Alternatively, a randomized controlled trial of transfer versus non-transfer to the ECMO centre for severely hypoxic infants cared for in non-ECMO level 3 nurseries could be considered. PMID- 2265018 TI - The value of C-reactive protein measurement in the diagnosis of neonatal infection. AB - We examined whether serum C-reactive protein (CRP) measurements used in conjunction with leucocyte counts help in the diagnosis of perinatally acquired and nosocomial infections in very preterm newborn infants. One hundred and twenty five infants born at a gestational age between 23 and 31 weeks with respiratory distress were studied at birth. A similar group of 85 infants beyond 3 days of age were also studied on 100 occasions for suspected infection. The diagnosis of proven or probable infection was correlated with abnormal haematology (leucopenia less than 5000/mm3, leucocytosis greater than 20,000/mm3 or ratio of immature forms to total neutrophils of greater than 0.2) and an elevated CRP (greater than 10 mg/L) singly or in combination. The sensitivity of an elevated CRP was relatively higher than abnormal haematology in both early and late infections and the sensitivity was highest when either test was abnormal. Similarly, the specificity, positive and negative predictive values and efficiency of an elevated CRP was relatively higher than abnormal haematology. The performance of the tests in 45 infants born at 23-28 weeks gestation was similar to that in 80 infants born at 29-31 weeks gestation. It was concluded that both CRP and leucocyte counts should be determined as they provide valuable information in the diagnosis of neonatal bacterial infection. PMID- 2265019 TI - A study of periventricular haemorrhage, post-haemorrhagic ventricular dilatation and periventricular leucomalacia in Chinese preterm infants. AB - Serial cranial ultrasound scans were performed in 178 preterm Chinese infants (gestation less than 35 weeks, birthweight less than 2000 g) to study the incidence, age of onset and associating risk factors of periventricular haemorrhage (PVH), and also the occurrence of post-haemorrhagic ventricular dilatation and periventricular leucomalacia (PVL). Sixty-four infants developed haemorrhage, giving an incidence of 36%. Among infants of birthweight less than 1500 and less than 1000 g the respective incidence was 52 and 69%. Seventy-two per cent (46 of 64) of haemorrhages were initially detected within the first 3 days of life, but delayed haemorrhage occurring after 1 week of age occurred in nine infants. In eight of these infants PVH had been shortly preceded by a major clinical disaster. Eleven perinatal factors were found to be significantly associated with PVH but only systemic hypotension showed a significant independent association. Post-haemorrhagic ventricular dilatation developed in 17 (46%) of the 37 infants who survived for more than 1 month after PVH. This was transient in 41%, persistent but stable in 29% and progressive in 29%. PVL was detected in eight infants who survived the initial period following PVH. PMID- 2265020 TI - Dialysis and renal transplantation in children: long term and recent experience. AB - The outcome of 38 children with endstage renal failure who entered a dialysis and renal transplant programme over a period of 16 years is reported. The initial care was given in an adult programme but in 1985 this was changed to a comprehensive and specifically paediatric programme. Patient survival was 97, 86 and 80% at 1, 5 and 10 years respectively. Thirty-four of the patients spent a mean period of 19 months (range 1-160 months) on dialysis with the preferred form of dialytic therapy being continuous ambulatory peritoneal dialysis. Primary cadaveric graft survival was 72 and 42% at 1 and 3 years respectively; although since 1985 1 year graft survival has risen to 90%. The major long term problems have been growth failure and poor social development. Eighty-seven per cent of children have been able to continue normal schooling, and of the 18 who have left school 14 (78%) are employed or undertaking tertiary education. Thus dialysis and transplantation has allowed not only excellent patient survival but also the achievement of satisfactory educational standards and subsequent employment for the majority of patients. PMID- 2265021 TI - Multiple hornet (Vespa orientalis) stings with fatal outcome in a child. AB - A case of multiple hornet stings is described with a rapidly fatal course due to the combination of massive haemolysis, coagulopathy, rhabdomyolysis, hyperkalaemia, acute renal failure, encephalopathy, hepatotoxicity and hyperglycaemia. These features of systemic envenomation can all be attributed to the toxic properties of Oriental hornet venom described in in vitro and in vivo experimental studies. Greater awareness of these features, aggressive treatment of hyperkalaemia and early institution of treatments such as peritoneal dialysis and plasma exchange may prevent fatalities in such cases. PMID- 2265022 TI - Is it safe to transport infants for extracorporeal membrane oxygenation? PMID- 2265023 TI - Evidence against a seronegative HTLV-I carrier rate among children. PMID- 2265024 TI - Structural homology between HIV-1 tat protein and various human proteins. PMID- 2265025 TI - Nucleotide sequence of a Ugandan HIV-1 provirus reveals genetic diversity from other HIV-1 isolates. AB - A Ugandan isolate of human immunodeficiency virus type 1 (HIV-1), designated U455, was adapted to growth in U937 cells, the provirus cloned into the lambda L47.1 vector, and its DNA sequence determined. The sequences of some of the U455 genes showed a marked divergence from those of North American and other African isolates. The sequenced clone was defective with single in-phase stop codons in the vpr and env genes and frame shift, resulting in a stop codon, within the vpu gene. PMID- 2265026 TI - In vitro characterization of a biologically active molecular clone of HIV-2NIH-Z containing a nef deletion and expressing a full-length transmembrane protein. AB - We have previously described the cloning and sequencing of a novel stain of human immunodeficiency virus type 2 (HIV-2) called HIV-2NIH-Z. A plasmid clone, pHIV2Z, containing the full-length provirus has now been constructed, and virus particles have been obtained upon transfection into COS-1 and H-9 cells. These particles can infect a number of T-cell lines and exert a cytopathic effect on fresh human and macaque peripheral blood lymphocytes. The cloned virus is biologically and morphologically indistinguishable from its parental uncloned strain as shown by restriction enzyme analysis, electron microscopy, and kinetics of infection. However, as shown by radioimmunoprecipitation assays, the cloned virus-infected cells express a full-length gp41 protein as predicted by the nucleotide sequence, whereas the wild-type parental strain expresses a truncated gp33 protein. Both the parental strain and the cloned virus possess a deletion encompassing the end of the nef gene within the U3 region which apparently does not affect their in vitro cytopathic and replicative capacities. PMID- 2265027 TI - Antibodies to HIV-1 nef(p27): prevalence, significance, and relationship to seroconversion. AB - A sensitive and specific enzyme-linked immunoassay for antibodies to the human immunodeficiency virus type 1 (HIV-1) nef gene product, p27, has been developed using recombinant Escherichia coli-derived protein from the LAV-1-Bru sequence. Of 92 HIV-1 infected hemophiliacs, 72 (78%) produced anti-nef antibodies in this assay; the early appearance of anti-nef prior to full seroconversion was a rare event in this population, occurring in only one subject (approximately 1%). Anti nef antibodies were not detected in any of 500 sera from 98 repeatedly HIV seronegative subjects who had been exposed to sexually transmitted modes of HIV infection (45 subjects) or through blood products (53 subjects). There was no significant association of titer or anti-nef antibody with protection from disease in HIV infection (p = 0.1). Although the nef protein is relatively immunogenic in natural infection, this study cannot confirm the previously reported high prevalence of anti-nef antibodies prior to seroconversion, nor the finding of anti-nef antibodies in HIV seronegative but exposed subjects. PMID- 2265028 TI - Interactive laser cytometric analysis of retroviral protein expression in HIV infected lymphocytic cell lines. AB - We have used interactive laser cytometry to investigate the expression of human immunodeficiency virus (HIV) envelope glycoproteins gp160, gp41, gp120, and the core protein p24 in the HIV-infected human lymphocyte cell lines H-9, CEM-SS, and C8166. This method allowed for the ultrasensitive detection of fluorescence signals at the single cell level and, when combined with specific anti-HIV antibodies, permitted unique quantitative detection of HIV antigens. Indirect immunofluorescence assays with monoclonal antibodies directed against gp120 revealed that a large proportion of lymphocytic cells expressed increased gp120 associated fluorescence consistent with HTLV-IIIRF infection. Certain monoclonal and polyclonal antibodies were also effective in quantifying gp160, gp41, and p24 expression. Expression of these antigens was found to vary significantly within 48 h. Significant loss (greater than or equal to 50%) of gp120 expression was observed when cells were treated with 1.0 microM AZT. The expression of the HIV associated protein markers gp160, gp41, and p24 was detectable 24 h after infection of C8166, a cord blood lymphocytic cell line. C8166 cells expressed an additional 6- to 10-fold increase in gp120 in 48 h as well as a 3- to 4-fold increase in gp160, gp41, and p24. AZT (0.01 and 0.1 microM) decreased the expression of gp120, gp160, and p24 in a dose-dependent fashion. This new application of interactive laser cytometry permits early, sensitive, and statistically based distinctions in the expression of HIV-associated antigens in infected target cells at the single-cell level, and allows detection of important changes in HIV-associated antigen expression and the kinectics thereof.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265029 TI - Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine. AB - The antiviral activity, uptake, and metabolism of 2',3'-dideoxyguanosine was investigated in human immunodeficiency virus- (HIV) infected and noninfected human cells. 2',3'-Dideoxyguanosine had anti-HIV activity (effective dose 50%: 0.1-1.0 microM) in H-9 and MT-2 cells. The addition of excess (greater than or equal to 30 microM) guanosine, deoxyguanosine, or 8-aminoguanosine had no effect on the anti-HIV activity of 2',3'-dideoxyguanosine. In [8-3H]2',3' dideoxyguanosine-exposed cells, the intracellular radioactivity was twofold higher than the extracellular. When guanosine, deoxyguanosine, or 8 aminoguanosine was preincubated or added simultaneously to 2',3' dideoxyguanosine, uptake of 2',3'-dideoxyguanosine was reduced by 28 to 34%, whereas addition of p-nitrobenzylmercaptopurine riboside (20 microM) had no effect. In metabolism studies using H-9 cells, dideoxyguanosine triphosphate could not be detected despite a 24-h incubation of 2',3'-dideoxyguanosine at effective anti-HIV concentrations. The addition of excess (greater than or equal to 30 microM) guanosine, deoxyguanosine, and 8-aminoguanosine, while inhibiting the catabolism of 2',3'-dideoxyguanosine, did not enhance the anabolic conversion of 2',3'-dideoxyguanosine to dideoxyguanosine triphosphate. Our failure to detect the formation of dideoxyguanosine triphosphate and the lack of reversal of antiviral effects by natural purine nucleosides raises questions on the role of this metabolite in the anti-HIV activity of 2',3'-dideoxyguanosine. PMID- 2265030 TI - The dilemmas faced by nurse practitioners. PMID- 2265031 TI - 1965-1990: 25th anniversary of nurse practitioners. A classic manuscript reprinted in celebration of 25 years of progress. Twelve paradoxes: a message for nurse practitioners. 1974. PMID- 2265032 TI - A collaborative approach to nursing research: Part I, The process. AB - Although many nurse practitioners may be interested in documenting aspects of their practice through research, resource and time constraints can limit the opportunity. Collaboration can be a practical and rewarding approach to making research feasible for clinicians. Under the auspices of a professional nursing organization, a group of San Francisco Bay area nurse practitioners conducted a survey designed primarily to increase membership in their organization. This article details the process by which the research was conducted and serves as a guide for clinicians about to undertake a similar project. PMID- 2265033 TI - A collaborative approach to nursing research: Part II, The findings. A profile of San Francisco Bay area nurse practitioners and their needs. AB - A collaborative research project conducted by nurse practitioners (NPs) was undertaken to establish a profile of NPs practicing in the San Francisco Bay area. The profile consisted of information regarding educational preparation, certification, employment status, salary, and practice characteristics. A mail survey of all Bay area NPs was implemented to obtain the information used in program planning and membership recruitment for the Primary Care Nurse Practitioner Interest Group of Region 12 of the California Nurses' Association. The results revealed the types of programs desired and common barriers to participation. Based on these findings, changes were made in the program format and offerings to make the organization more responsive to the needs of NPs. PMID- 2265034 TI - The use of antidepressant medication: a guide for the primary care nurse practitioner. AB - Antidepressant medications are being used to treat a broad spectrum of depressive syndromes. Newer uses of antidepressants are briefly presented. The mechanism of action and side-effect profile of antidepressants are outlined to help the nurse practitioner choose which antidepressant to use. Pharmacologic treatment is discussed. A case presentation illustrates important aspects of discontinuing antidepressant medication. PMID- 2265035 TI - Nurse practitioners develop leadership in community problem-solving. AB - If nurse practitioners are to become agents of change within the community, a shift in focus from the individual/family/caseload to one that includes population/community will be required. The nurse practitioner will need to develop the skills of community coalition building and grantsmanship. Graduate preparation in primary care nursing can provide an opportunity to develop the necessary knowledge and skills for leadership in community problem-solving by incorporating reality-based learning experiences into the curriculum. A model for guiding graduate study is presented. PMID- 2265037 TI - Candida pharyngitis. PMID- 2265036 TI - Report of the national survey of the American Academy of Nurse Practitioners, Part IV: Practice characteristics and marketing activities of nurse practitioners. AB - This report includes information about the practice characteristics of nurse practitioners according to location of practice and specialty. Information regarding hospital privileges, contracts, job descriptions, evening call, practice support and marketing are included. PMID- 2265038 TI - The National Health Service Corps: new opportunities for nurses on the horizon. PMID- 2265039 TI - Videotapes: are they helpful in the practice setting? PMID- 2265040 TI - The nurse teaches the doc. PMID- 2265041 TI - Developments in the safe use of high frequency jet ventilation. PMID- 2265042 TI - Measurement of end-expiratory pressure during transtracheal high frequency jet ventilation for laryngoscopy. AB - An anaesthetic technique using high frequency jet ventilation has been proposed for direct laryngoscopy, but this may expose the patients to the risk of barotrauma. In order to assess this risk, we have measured end-expiratory airway pressure (EEP) through the injector using two three-way solenoid valves mounted in series. At the end of insufflation the first valve was switched off and the apparatus deadspace connected to atmosphere through a large exit port during an adjustable time (decompression time). Then the second valve was switched off and the injection line connected to a transducer, allowing measurement of EEP through the injector. The accuracy of this measurement was tested against airway pressure measured directly in the trachea (Pt) in a lung model. Provided that the decompression time was long enough (70 ms) and the apparatus deadspace was small (6 ml), the difference between EEP and Pt was less than 1 cm H2O for frequencies up to 5 Hz. A clinical evaluation was performed in 64 patients under general anaesthesia before laryngoscopy. EEP correlated with end-expiratory pulmonary volume above apnoeic FRC inferred from abdominal and thoracic displacements. At jet frequencies up to 5 Hz, the correlations between these two variables were satisfactory (r greater than 0.88), suggesting that EEP is a good indicator of pulmonary overdistension. PMID- 2265043 TI - Ultrasound assessment of the position of the tongue during induction of anaesthesia. AB - Tongue position was assessed in 15 female patients at induction of anaesthesia with either thiopentone or propofol. A video recording of a midline sagittal section of the tongue was made using an ultrasound transducer placed below the chin, and representative figures analysed by an observer who was not aware of the patient's state. In 11 satisfactory recordings, the tongue movement was inconsistent in direction and not more than 8 mm in the anterior tongue and 6 mm in the posterior tongue. The movements detected did not suggest that the tongue is likely to be an important cause of airway obstruction on induction of anaesthesia. PMID- 2265044 TI - Effects of enflurane and isoflurane in air-oxygen on changes in thermal balance during and after surgery. AB - The temperatures in the aural canal (core), skeletal muscle and skin surface were measured during anaesthesia and surgery in 32 healthy females undergoing total abdominal hysterectomy and for 4 h after operation. The patients were allocated randomly to one of four groups according to the end-tidal concentration of volatile anaesthetic: 1 MAC isoflurane, 1 MAC enflurane, 1.8 MAC isoflurane and 1.8 MAC enflurane. The lungs were ventilated with an air-oxygen mixture. Neuromuscular block was produced with pancuronium. Room temperature and i.v. fluid administration were standardized. Aural canal, muscle and mean skin temperatures decreased significantly in all groups during surgery (P less than 0.001). The decrease in core and muscle temperatures, and mean body heat was significantly greater in the 1.8 MAC groups than in the 1 MAC groups for both volatile agents (P less than 0.001). However, there was a significantly greater decrease in core temperature and mean body heat in the isoflurane compared with the enflurane group (P less than 0.026). Body temperature returned to preoperative values during the recovery period. There was a significantly greater rate of rewarming during the first 1 h of recovery in the 1.8 MAC groups compared with the 1 MAC equivalent (P less than 0.001), and this was independent of the volatile agent used. The present results are compared with those reported previously in which nitrous oxide was added to the volatile agents. The decrease in body temperature depends upon the concentration of vapour used. However, it appears that isoflurane, without nitrous oxide, caused greater loss of body heat than enflurane. PMID- 2265045 TI - Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study. AB - The effect of pretreatment with fentanyl on the pharmacokinetics of a single bolus of propofol was studied in 17 female patients (mean age 35 yr), ASA grade I. Eight patients received fentanyl 1.5 micrograms kg-1 5 min before induction of anaesthesia. In all patients anaesthesia was induced with propofol 2.5 mg kg-1 and maintained with halothane and nitrous oxide in oxygen. Pretreatment with fentanyl resulted in prolonged apnoea in all eight patients compared with three of nine patients in the control group. The pharmacokinetic values for propofol were described by a three-compartment mammillary model with rapid distribution phases (T1/2 alpha mean (SEM) 3.1 (2.0) min and T1/2 beta 44 (9.1) min) and a slower final phase of T1/2 gamma 520 (96) min. The clearance of propofol was rapid (mean 1.6 (0.24) litre min-1). Propofol was distributed initially into a relatively large central compartment (mean 23.7 (6.6) litre) and was extensively redistributed (mean Vss 593 (157) litre). There was no difference in the pharmacokinetic profile of propofol between the two groups. PMID- 2265046 TI - A computer designed graph for administration of atracurium by i.v. infusion. AB - A bi-exponential mathematical computer model was used to develop a guidance graph for atracurium infusions. The model permitted variation in infusion rates, in pharmacokinetic parameters and in "effect" thresholds. Systematic experiments revealed a relationship between the rate of recovery from a fixed bolus loading dose and the most appropriate initial infusion rate. This relationship was expressed as a guidance graph or "ready reckoner". The quality of guidance was assessed in 50 anaesthetics, given consecutively. In 39 patients optimal myoneural block for surgery was maintained for the duration of the infusion without adjustments or supplementary bolus doses. The mean operating time was 92 min and the mean duration of infusion was 59 min. PMID- 2265047 TI - Effects of halothane, enflurane and isoflurane anaesthesia on renal plasma flow. AB - Effective renal plasma flow (ERPF) and linear cardiac output (aortic blood velocity) were measured in 15 patients who received halothane, enflurane or isoflurane in oxygen. All three agents caused a significant reduction in ERPF (P less than 0.05) and the effect was greater at 1.25 MAC than at 0.75 MAC. No significant difference was demonstrated between the agents. Linear cardiac output did not change significantly during the study, suggesting that the observed reduction in ERPF was not caused by cardiovascular depression. PMID- 2265048 TI - Factor analysis in difficult tracheal intubation: laryngoscopy-induced airway obstruction. AB - We have studied eight patients with a history of difficult tracheal intubation, using x-ray laryngoscopy and local anaesthesia, a curved Macintosh blade and a standard intubating position. The view obtained was better than recorded previously during general anaesthesia in two patients, and in a third the x-ray showed that positioning the blade tip beneath the epiglottis would have improved vision, suggesting that reproducibility of the assessment may not be consistent. The "ease of intubation" and "complementary" angles may be helpful in the assessment of such patients. A "peardrop" effect is described whereby during laryngoscopy, the epiglottis became pressed against the posterior pharyngeal wall as a result of tongue compression. In the absence of muscle paralysis, removal of the blade caused immediate correction. However, during anaesthesia with neuromuscular block it is suggested that this not only occurs more readily but, may not correct when the blade is removed. Iatrogenic airway obstruction during moderately difficult tracheal intubation may be common and should be anticipated. PMID- 2265049 TI - Pain relief after thoracotomy. PMID- 2265050 TI - Factor analysis in patients with a history of failed tracheal intubation during pregnancy. AB - Eight patients with a history of failed tracheal intubation during pregnancy were investigated by x-ray laryngoscopy after delivery. Partial elevation of the epiglottis with no view of glottic structures was found in five patients who were therefore considered to still present difficulty. In each of these five patients the blade tip failed to make contact with the hyoid and in four this was explained by the tongue being compressed into a pear shape such that it prevented sight of the larynx. Relatively few abnormal anatomical indices were seen in these patients and this was in keeping with the level of difficulty encountered. An angular measure of jaw protrusion from a line joining the upper incisors and a point just above and anterior to the vocal cords, to the mid-point on the inner surface of the mandible was useful: the lower angle of this triangle was as important as the angle at the incisors. PMID- 2265051 TI - Myotonic and neuromuscular blocking effects of increased doses of suxamethonium in infants and children. AB - The myotonic effects and duration of action of several doses of suxamethonium were determined in 24 infants and 16 children during thiopentone-fentanyl-nitrous oxide anaesthesia. Infants received suxamethonium 2, 3 or 4 mg kg-1; children received 1 or 2 mg kg-1. The increase in muscle tone during onset of neuromuscular block was independent of dose. Onset of block was faster in children who received suxamethonium 2 mg kg-1 compared with those who received 1 mg kg-1, and in infants given 2 mg kg-1 than in children given the same dose. Compared with adults given suxamethonium 1 mg kg-1, infants required 3-4 mg kg-1 and children at least 2 mg kg-1 to produce 6-8 min of neuromuscular block. These results provide a clear indication for increasing the intubating doses of suxamethonium in infants and children, and a explanation for the unduly high rate of "masseter spasm" in some paediatric centres. PMID- 2265052 TI - Prevention of hypotension following spinal anaesthesia for elective caesarean section by wrapping of the legs. AB - Twenty-four parturients undergoing elective Caesarean section were allocated randomly to have the legs wrapped with elasticated Esmarch bandages immediately following spinal anaesthesia or to serve as controls. Significant hypotension (systolic arterial pressure less than 100 mm Hg and less than 80% of baseline value) was treated with i.v. ephedrine in 5-mg boluses. Leg wrapped patients had a significantly (P = 0.0033) lower incidence (16.7%) of hypotension than controls (83.3%). Only two patients in the leg wrapped group required ephedrine compared with 10 in the control group. Systolic arterial pressure was significantly (P less than 0.05) less in control subjects at 4, 5 and 6 min following spinal injection. No patient in the leg wrapped group became hypotensive following removal of the elasticated bandages. PMID- 2265053 TI - Effect of propofol on brain retraction pressure and cerebral perfusion pressure. AB - We have studied the effect of propofol, at a rate of 30 mg kg-1 h-1 for 5 min reducing to 6 mg kg-1 h-1 for a further 5 min, on brain retraction pressure (BRP) in 15 patients undergoing craniotomy. The response of BRP showed two distinct patterns. BRP was reduced by an average of 3.3 mm Hg (P = 0.005). Mean arterial pressure was reduced in all patients by an average maximum of 28.3 mm Hg (P = less than 0.001), which caused a significant reduction in cerebral perfusion pressure (CPP) by 22.9 mm Hg (P less than 0.001). It is concluded that, by reducing BRP, propofol provided suitable conditions for intracranial surgery, but care should be taken to avoid excessive reduction in CPP. PMID- 2265054 TI - Unconsciousness associated with midazolam and erythromycin. AB - An 8-yr-old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy. Sixty minutes after premedication with oral midazolam 0.5 mg kg-1 and oral atropine 0.03 mg kg 1, an infusion of erythromycin 400 mg was started. When 200 mg of erythromycin had been infused, the patient lost consciousness, but other vital functions remained normal. After 45 min, he awakened spontaneously. At the time the plasma concentration of midazolam was 134 ng ml-1. In order to investigate possible interactions between midazolam and erythromycin, we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery. The plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin. The altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug, erythromycin. PMID- 2265055 TI - Concentrations of atracurium and laudanosine in cerebrospinal fluid and plasma in three intensive care patients. AB - We have measured concentrations of atracurium and laudanosine in cerebrospinal fluid (CSF) and plasma in three intensive care patients receiving atracurium infusions of 22.5-106 h duration to maintain neuromuscular block. Two patients had suffered severe closed head injuries and the third patient had developed respiratory failure following the clipping of two intracranial aneurysms. The total dose of atracurium given was 14.3-136.6 mg kg-1; rate of infusion was 0.6 1.38 mg kg-1 h-1. Plasma concentrations of atracurium and laudanosine were 0.73 3.11 micrograms ml-1 and 0.48-8.65 micrograms ml-1, respectively; CSF concentration of laudanosine was 70-440 ng ml-1. No adverse effects attributable to these concentrations of laudanosine were observed. PMID- 2265056 TI - Massive histamine release in a patient with systemic mastocytosis. AB - We have measured plasma histamine concentrations, systemic vascular resistance, cardiac output and arterial pressure during laparotomy in a patient with systemic mastocytosis. The patient developed vasodilation and hypotension during surgery, associated with a massive increase in plasma histamine concentration. PMID- 2265057 TI - Clinical observations on Org 9426. PMID- 2265058 TI - Management of major trauma. PMID- 2265059 TI - Halothane hepatitis. PMID- 2265060 TI - A second time-study of the anaesthetist's intraoperative period. PMID- 2265061 TI - Community prevention efforts to reduce the spread of AIDS associated with intravenous drug abuse. AB - Drug abusers currently represent almost 30% of AIDS cases reported to the Centers for Disease Control. Intravenous drug abusers have been recognized as a major vector for the spread of HIV to the general public. Considering the high levels of AIDS risk behaviors among intravenous drug abusers, prevention efforts to reduce risk are a priority. Since community prevention approaches have been found effective with other target populations, this article considers community prevention as an AIDS reduction strategy. Consensus recommendations developed by a panel of researchers and practitioners who met at the National Institute on Drug Abuse in 1988 are presented. Specific recommendations for community prevention with intravenous drug abusers and their sex partners are introduced along with suggested research initiatives. PMID- 2265062 TI - The global AIDS situation, 1990. PMID- 2265063 TI - World AIDS Foundation announces new grants program in developing countries. PMID- 2265064 TI - Comparative pharmacokinetics of DNA lesion formation and removal following treatment of L1210 cells with nitrogen mustards. AB - The kinetics of formation and removal of DNA interstrand crosslinks (ISC), DNA protein crosslinks (DPC), and single strand breaks (SSB) by several nitrogen mustards were compared in order to determine the degree to which lesion selectivity may vary. The kinetic measurements using DNA alkaline elution methodology were obtained in mouse L1210 cells treated with mechlorethamine (HN2), phenylalanine mustard (L-PAM), uracil mustard (UM), 6-methyl-UM, and quinacrine mustard (QM). The ISC or DPC challenge delivered to cells was gauged on the basis of the kinetics as either total ISC or DPC produced, or as the area under the lesions versus time curve (AUC). By either measure (excepting QM), ISC correlated well with loss of colony survival, whereas DPC did not. The ISC/DPC ratio may therefore be a useful index of lesion selectivity. This ratio was significantly greater for 6-methyl-UM than for HN2. The ratio was also greater for L-PAM than for HN2 but only when gauged by AUC; this was attributable to an unusually slow rate for ISC removal in the case of L-PAM. The preferential reaction of UM at some 5'-GC-3' sites in purified DNA had suggested that UM might produce ISC with increased efficacy. UM, however, was somewhat less efficacious in ISC production than was 6-methyl-UM, which lacked selectivity for alkylation at 5'-GC-3'. QM was the only compound that produced detectable SSB, and the SSB were so numerous that ISC could not be quantitated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265065 TI - Clinical features of Sjogren's syndrome. PMID- 2265066 TI - Prognosis of systemic lupus erythematosus and factors that affect it. PMID- 2265067 TI - Clinical features and complications of systemic lupus erythematosus, and assessment of disease activity. PMID- 2265068 TI - Treatment of systemic lupus erythematosus in adults and children. PMID- 2265069 TI - Molecular genetics of systemic lupus erythematosus and Sjogren's syndrome. PMID- 2265070 TI - Animal models of systemic lupus erythematosus and Sjogren's syndrome. PMID- 2265071 TI - Lymphocyte biology in lupus. PMID- 2265072 TI - Treatment, pain, and epidemiology of osteoarthritis. PMID- 2265073 TI - Biochemical markers of osteoarthritis. AB - The recent attempts to discover markers of early degenerative joint disease need to be considered from several viewpoints. 1. Our basic understanding of events in joint disease has increased considerably as a result of these studies, and the information gained will collectively contribute to future developments. 2. It should be clearly stated that at present, no marker has been found in biologic fluids that can be used for diagnosing and monitoring degenerative joint disease. 3. Current data provide optimism that the analysis of biologic fluids, perhaps by using more than one marker or fluid, will in the future offer clinically useful information allowing an earlier diagnosis and more appropriate monitoring of the disease. 4. Genetic markers will provide information on subpopulations of patients susceptible to disease development, which should allow early intervention in disease activity and progression in these patients. PMID- 2265074 TI - Articular cartilage research. PMID- 2265075 TI - Gout and hyperuricemia. PMID- 2265076 TI - Calcium pyrophosphate deposition disease and other crystal deposition diseases. PMID- 2265078 TI - Lupus erythematosus and dermatomyositis. PMID- 2265077 TI - Juvenile chronic arthritis, juvenile rheumatoid arthritis, and inflammatory arthropathies of childhood. PMID- 2265079 TI - Kawasaki disease and vasculopathies. PMID- 2265080 TI - Musculoskeletal manifestations of infectious disease in children. PMID- 2265081 TI - Miscellaneous conditions associated with musculoskeletal complaints in children. PMID- 2265082 TI - Congenital and metabolic abnormalities of the musculoskeletal system. PMID- 2265083 TI - Rheumatic fever. PMID- 2265084 TI - Systemic lupus erythematosus. PMID- 2265086 TI - Pediatric and heritable disorders. PMID- 2265085 TI - Osteoarthritis and crystal deposition diseases. PMID- 2265087 TI - Epidemiological practice in the health services systems. PMID- 2265088 TI - Langerhans cells but not monocytes are capable of antigen presentation in vitro in corticosteroid contact hypersensitivity. AB - Corticosteroids suppress delayed-type hypersensitivity (DTH) reactions in vivo and impair lymphoid cell functions in vitro. In contact hypersensitivity (CHS) to corticosteroids, however, the corticosteroids are capable of inducing DTH responses in vivo. The present study examined the capacity of corticosteroids to induce in vitro proliferation of T lymphocytes from patients with CHS to corticosteroids. With peripheral blood mononuclear adherent cells as antigen presenting cells (APC) and hydrocortisone-17-butyrate (H-17-B) as hapten, no proliferation responses were detected of T lymphocytes from patients with CHS to H-17-B. However, when epidermal Langerhans cells (LC) were used as APC, weak proliferation responses were observed. PMID- 2265089 TI - The changing face of dermatology out-patient referrals in the south-east of Scotland. AB - A study of out-patient dermatological services (NHS and private) in the south east of Scotland was carried out by medical staff in the Department of Dermatology in Edinburgh during the month of November 1988. The aim was to assess changes in referral patterns and workload compared with the findings of an identical investigation undertaken in November 1981. Of particular interest were the possible effects of recent publicity campaigns aimed at increasing public awareness about skin cancer. The medical complement of the dermatology department had changed minimally since 1981 and the population increase in the south-east of Scotland over the same period was 1.5%. During November 1988 1592 new patients and 2037 review patients were seen. This represented an increase of 29.2% and 28.3%, respectively, since 1981. The most striking changes in diagnostic groups were a 173% rise in new cases presenting with benign tumours (excluding viral warts) and a 106% increase in new patients with malignant tumours. Viral warts and eczema were, as in 1981, the second and third most common diagnostic categories amongst new patients. There was a 98% increase in the number of surgical procedures performed on new patients compared with 1981. We conclude that the substantial increase in numbers of both benign and malignant tumours and the consequent doubling in surgical treatments was due to increased public awareness and concern about skin cancer. PMID- 2265090 TI - Validation of Sickness Impact Profile and Psoriasis Disability Index in Psoriasis. AB - A prospective cross-sectional questionnaire study of 32 patients with psoriasis was carried out in order to validate the use of the Sickness Impact Profile (SIP) in psoriasis and compare its sensitivity with the Psoriasis Disability Index (PDI). Overall PDI scores, but not overall SIP scores, correlated well with PASI scores (P less than 0.05). There was good correlation between the PDI and overall SIP scores (P less than 0.01). Psychosocial factors are more severely impaired than physical activities in patients with psoriasis. It is now possible to directly compare the disability experienced by psoriatic patients with that experienced by patients suffering from other systemic diseases, using the SIP. The PDI is an appropriate method to give a rapid overall measure of psoriasis disability. PMID- 2265091 TI - Pigmented spindle cell naevus. AB - We report 22 cases of pigmented spindle cell naevus (PSCN). The usual appearance of these naevi is that of a heavily pigmented papule found mostly on the legs of young patients. Histologically, PSCN was characterized by symmetrical proliferation of spindle-shaped pigmented melanocytes grouped in large junctional nests. Pagetoid spread of single cells in the overlying epidermis was frequently found. In our opinion, PSCN is a distinctive benign acquired melanocytic naevus that in the past has been frequently misdiagnosed as atypical Spitz naevi or malignant melanoma. PMID- 2265092 TI - Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare. AB - Using an antibody to S100 protein, the number of dendritic cells above the basal layer in the epidermis was assessed in necrobiosis lipoidica and granuloma annulare. A statistically significantly higher number of these cells was found within the epidermis in necrobiosis lipoidica compared with granuloma annulare and normal skin. The numbers were similar to those seen in sarcoidosis and tuberculous reactions in the skin, which raises the possibility of an immune pathogenesis for necrobiosis lipoidica. PMID- 2265093 TI - Anxiety and depression in patients with chronic urticaria and generalized pruritus. AB - Thirty-four dermatology out-patients with chronic idiopathic urticaria and 34 with idiopathic generalized pruritus were investigated using standardized self assessment psychological questionnaires to determine the incidence of significant symptoms of depression and anxiety. These patients were compared with age- and sex-matched but otherwise unselected general dermatology out-patients. Using the Beck depression inventory, significantly more patients with generalized pruritus (32.4%) had depressive symptomatology (score greater than 14) than controls (13.2%, P less than 0.05). Although more patients with chronic urticaria had depressive symptomatology (14.7%) than controls (4.4%), the difference was not statistically significant. Using the Speilberger state-trait anxiety inventory there were no significant differences between the patients with pruritus or urticaria and their controls with respect to state or trait anxiety scores above the upper 90% probability limit for the general population. Thus, significant depression may be expected in a substantial proportion of patients with idiopathic generalized pruritus but in a relatively small proportion of those with chronic urticaria. PMID- 2265094 TI - Clear ultraviolet blocking lenses for use by PUVA patients. AB - It is well recognized that patients receiving photochemotherapy (PUVA) need to wear UV-blocking sunglasses on the day of ingestion of 8-methoxypsoralen. For many patients the wearing of tinted sun-glasses causes difficulties because they interfere with colour perception, reduce definition in conditions of low background light and often because they are considered 'cosmetically unacceptable'. In this study the UV-blocking properties of a number of lenses with little or no tint were assessed. The following lenses or lens coatings were found to be suitable for use by PUVA patients: Orcolite UV 400, Orma UVX, Rodenstock Lambda 400, Sola UV Gard 400 and Polaroid polarizing lenses. PMID- 2265095 TI - Topical treatment of necrotic foot ulcers in diabetic patients: a comparative trial of DuoDerm and MeZinc. AB - An open randomized controlled study was carried out of 44 diabetic patients with necrotic foot ulcers treated with adhesive zinc oxide tape (MeZinc) or with an adhesive occlusive hydrocolloid dressing (DuoDerm). Fourteen of the 21 patients treated with MeZinc had their necrotic ulcers improved by at least 50% compared to six out of 21 with the hydrocolloid dressing (P less than 0.025). Fifteen patients showed an increase in the area of necrosis during the course of the 5 week study and of these, 10 had been treated with the hydrocolloid dressing. PMID- 2265096 TI - Perianal streptococcal cellulitis with penile involvement. AB - Perianal streptococcal cellulitis is described occurring in a 5-year-old boy. The condition also involved the penis and presented as a possible case of sexual abuse. The correct diagnosis was established by culturing beta-haemolytic streptococci group A from the penile and perianal skin. PMID- 2265097 TI - Angiotropic B-cell lymphoma (malignant angioendotheliomatosis): failure of systemic chemotherapy. AB - A 65-year-old female with angiotropic B-cell lymphoma is reported. Despite the absence of systemic involvement on formal staging and the favourable response of the cutaneous lesions to triple systemic chemotherapy with prednisolone, vincristine and cyclophosphamide, postmortem findings showed that death was due to widespread disease dissemination. PMID- 2265098 TI - Annual meeting of the British Society for Investigative Dermatology. Newcastle, September 1990. Abstracts. PMID- 2265099 TI - Increased frequency of HLA-DR2 in patients with Darier's disease. PMID- 2265101 TI - Varicella bullosa in an adult. PMID- 2265100 TI - Sensitization as a result of a religious ritual. PMID- 2265102 TI - A brief historical development of vascular access for hemodialysis. AB - Diligent laboratory and clinical research has been the key to the progress that has been made in the development of vascular access for hemodialysis. Presently, there are a number of access techniques that work fairly well. None are ideal. The momentum of the progress during the past half century can only encourage one to look toward the future. Treatment of patients in years to come will evolve from the foundation of knowledge and experience that has been laid as well as the implementation of future discoveries. It can be anticipated that some things will change. Perhaps through such discoveries as improved implantable dialysis devices, newer surgical techniques, different synthetic materials, drugs, and/or medical therapy, advances will occur. The work in renal transplantation may be perfected thereby eliminating the need for hemodialysis. However, gradual, rapid, or unexpected progress will be made. Fortunately, the many crucial milestones that have occurred will provide a strong base for future discoveries. PMID- 2265103 TI - Effort thrombosis. AB - Venous thrombosis of the upper extremity can be very minor (superficial phlebitis from IV's) or quite dramatic (effort thrombosis of the axillary or subclavian veins). Rarely is it life threatening. Long-term sequelae are not seen. PMID- 2265104 TI - The use of epidural analgesia in postoperative vascular surgical patients. AB - Patients undergoing vascular surgical procedures can be higher risk patients. The goal is to provide the best pain management modality with the fewest significant side effects. Nurses can make a critical difference in the successful use of epidural analgesia by understanding how it works, monitoring for and treating side effects and complications that may occur, providing patient education, monitoring pain control and assuring patient safety. Overall, epidural analgesia does provide excellent analgesia and has many benefits for the vascular surgical patient. PMID- 2265105 TI - Administration of sub-cutaneous (sub-cu) heparin. PMID- 2265106 TI - Nurses together in caring. PMID- 2265107 TI - LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia. AB - The newly produced monoclonal antibody (mAb) LF61 detects a molecule restricted to hairy cell leukaemia (HCL) among B-cell non-Hodgkin's lymphomas. In particular, the percentage of LF61 + HCL cells in different cases ranges from 10% to 100%. In normal lympho-haemopoietic tissues LF61 reacts with only about 2% of T-cells, mostly of the CD8 subset in the peripheral blood, extrafollicular areas of the tonsil, red pulp of the spleen and thymic medulla. Expression of the LF61 molecule is observed following stimulation of peripheral blood lymphocytes with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), suggesting that it represents an activation antigen. Due to its restricted reactivity with a small subset of normal CD8 + T-cells, LF61 in combination with a CD22 mAb is highly suitable for monitoring residual disease in interferon or deoxycoformicin-treated HCL patients. Polyacrylamide gel gradient electrophoresis shows that LF61 precipitates a 150 kDa, 125 kDa, 105 kDa trimeric molecule from the surface of HCL cells. Immunohistological and immunobiochemical results show that this molecule is the same as the one recognized by the still unclustered anti-HCL mAb B-ly7. PMID- 2265108 TI - Micro-osteoclast resorption as a characteristic feature of B-cell malignancies other than multiple myeloma. AB - Multiple myeloma (MM) is characterized by the presence of lytic bone lesion and frequent hypercalcaemia. These are due to an excessive osteoclastic resorption in association with a low bone formation, as demonstrated by bone histomorphometry. Conversely, B-cell malignancies other than MM are rarely associated with lytic bone lesion and/or hypercalcaemia. In this study we have analysed quantitative bone histology in 65 patients with B-cell malignancies other than MM at diagnosis: chronic lymphocytic leukaemia (CLL, n = 20), non-Hodgkin's lymphoma (NHL, n = 25), Waldenstrom's disease (WD, n = 14), hairy cell leukaemia (HCL, n = 6). Fifty patients presented no clinical evidence of increased bone resorption, including no lytic bone lesions radiologically detectable and/or no hypercalcaemia. 80% of these patients (40/50) had increased bone resorption parameter using quantitative bone histology, including 19/29 (65.5%) patients with CLL or WD and 21/21 (100%) patients with NHL or HCL (P less than 0.01). As a control group, seven patients lacking bone marrow involvement on bone sample presented no excessive bone resorption. However, eight patients presented lytic bone lesions and/or hypercalcaemia. All of these patients had increased resorption parameters with high numbers of osteoclasts per surface trabecular bone (mean = 35.3), as opposed to the patients lacking lytic bone lesions and/or hypercalcaemia (mean = 6.6, n = 28) and to normal individuals (mean +/- SD = 3.8 +/- 1.7 and 6.3 +/- 2.6, respectively before and after 60 years). In all the cases, excessive histologic bone resorption was mediated by mononuclear small osteoclasts (mean osteoclast length +/- SD = 27.3 +/- 4.1 as compared to normal range = 35.0 +/- 1.0, P less than 0.001). In different in vitro models, these small mononuclear osteoclasts are considered as progenitors. These data suggest an abnormal osteoclast differentiation in B-cell malignancies other than MM, probably due to differences in the production of local factors acting on bone remodelling. PMID- 2265110 TI - Osteoblast stimulation in multiple myeloma lacking lytic bone lesions. AB - The reasons why some patients with multiple myeloma (MM) do not develop severe bone loss, or even develop sclerotic bone lesions, remain unclear. In order to answer this question at the cellular and tissue level, we evaluated the histological bone condition of 10 patients with MM who never developed lytic bone lesions during the course of their disease (including two patients with sclerotic MM). Myeloma-induced bone changes in the close vicinity of myeloma cells were evaluated by quantitative histology (bone histomorphometry). All 10 patients presented a significantly increased osteoblastic activity. This was associated with an increased bone resorption in seven of the 10 cases. Three patients had a pure osteoblastic presentation. These features were the reverse of the pattern observed in seven patients with lytic bone lesions: increased bone resorption with decreased bone formation. Almost all of these 10 patients showing excessive osteoblastic activity had increased serum bone gla protein levels, a specific marker of bone formation. Finally, 90% of these patients were lambda MM (70% of them were IgG lambda MM), an immunoglobulin subtype previously associated with the sclerotic MM variants. In conclusion, a subset of patients with MM never develop severe bone loss because of the stimulation of osteoblastic activity. These patients belong to the same family as osteosclerotic MM, presenting more frequently the IgG type and lambda subtype. PMID- 2265109 TI - Interleukin-6 is a cofactor for the growth of myeloid cells from human bone marrow aspirates but does not affect the clonogenicity of myeloma cells in vitro. AB - Several groups have claimed that IL-6 is a growth factor for human myeloma cells in vitro. Bone marrow aspirates from 30 patients at different stages of treatment with VAMP/high dose melphalan, were examined for myeloma colony formation (MY CFUc) using a clonogenic assay in vitro. Myeloma cells from 16/30 patients produced MY-CFUc in our assay system, which uses heavily irradiated HL60 cells as an underlay in soft agar. These heavily irradiated cells were shown to be essential for the inhibition of granulocyte-macrophage colonies (GM-CFUc). The addition of recombinant human IL-6 (10 ng/plate) reduced the number of bone marrow samples which produced MY-CFUc from 16 to six. Furthermore, the addition of antibody to IL-6 (1 microgram/plate) failed to inhibit MY-CFUc from 6/7 samples. Conditioned medium from human peripheral blood mononuclear cells (PBMC CM) contains approximately 2 ng/ml IL-6 and can be used to stimulate the growth and maintenance of the B9 murine IL-6 dependent hybridoma cell line. Recombinant human IL-6 supported the growth of B9 cells in a clonogenic assay and growth was inhibited by anti-IL-6 in the presence of rhIL-6 or PBMC-CM. Mononuclear cells from a second group of myeloma patients were cultured in soft agar in a mixture of PBMC-CM and fresh growth medium. Nine of the 10 samples produced myeloid colonies which consisted of granulocytes, monocytes and macrophages and the number of colonies was reduced by at least 50% in 6/8 samples when anti-IL-6 was added to the cultures. In no instance were MY-CFUc produced. Also, conditioned medium from the bladder carcinoma cell line 5637, which is used routinely as a source of granulocyte-macrophage colony stimulating factor (GM-CSF), contains approximately 4 ng/ml IL-6. Although rhIL-6 failed to stimulate GM-CFUc in the absence of other growth factors, addition of anti-IL-6 to cultures containing a suboptimal amount of 5637-CM reduced the number of colonies by 50%. These data provide evidence that IL-6 is a cofactor for the growth of myeloid precursors but does not affect the proliferation of human myeloma cells in vitro. PMID- 2265111 TI - Interleukin-1 is one factor which regulates autocrine production of GM-CSF by the blast cells of acute myeloblastic leukaemia. AB - The role of interleukin-1 (IL-1) as a regulator of the autonomous growth of the blast cells of acute myeloid leukaemia (AML) has been studied on samples isolated from 15 patients. In nine out of 10 patients with evidence of partial autonomous blast cell growth. IL-1 further stimulated cell growth in both suspension culture and in a clongenic assay. IL-1 also stimulated cell growth in two out of three cases with no evidence of autonomous growth whereas no additional stimulation was observed in two cases with totally autonomous growth. In blast cells stimulated by IL-1, synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) was increased and the proliferative response to IL-1 was inhibited by an antibody to GM-CSF. In all samples with evidence of autonomous growth, blast cell conditioned medium (BCCM) contained IL-1 activity (range 0.7-74.2 units ml) and a polyclonal antibody to IL-1 markedly inhibited autonomous growth in four samples. BCCM from three of these four samples contained GM-CSF, the synthesis of which was suppressed when BCCM was prepared in the presence of anti-IL-1. Our data suggests that endogenous IL-1 is an important factor in the regulation of the production of GM-CSF and hence of autonomous growth of AML blasts, but that other mechanisms regulating GM-CSF production may exist. PMID- 2265112 TI - Purification and characterization of a pi class glutathione S-transferase from human leukaemic cells. AB - The glutathione S-transferases are a group of enzymes involved in the detoxification of a wide range of xenobiotics. Elevation of the level of activity of glutathione S-transferases within the cytosol has been associated with the development of resistance to a number of cytotoxic drugs, including some commonly used in the treatment of leukaemia. In this paper we describe the purification and characterization of an anionic (p class) form of the enzyme from the peripheral blood of patients with acute myeloid leukemia, chronic myeloid leukaemia, and acute lymphocytic leukaemia and the spleen of a patient with chronic lymphocytic leukaemia. We present evidence that the form of enzyme purified closely resembles pi class glutathione S-transferase purified from human placenta. Immunoblotting performed on cytosol from the leukaemic cells from a range of cases of leukaemia at presentation, or on treatment, demonstrated that this form of glutathione S-transferase was the predominant isoenzyme expressed in all cases studied. However, in the limited number of cases studied there was no correlation between the level of expression and response to chemotherapy, suggesting that increased expression of pi class GST is not the sole cause of resistance to bifunctional alkylating agent in human leukaemias. PMID- 2265113 TI - Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia. AB - A randomized, double-blind placebo-controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony-stimulating factor (hM-CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM-CSF treated and 59 placebo control patients. HM-CSF was administered at a daily dose of 2 x 10(5) units/kg from day 1 to day 14 after BMT. Significant differences between hM-CSF and control patient were found in the recovery time to greater than 0.5 x 10(9) granulocytes/l and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft-versus-host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24-36 months after BMT in patients with acute lymphocytic, acute nonlymphocytic, or monocytic leukaemia. The results of this trial show that human M-CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD. PMID- 2265114 TI - Definition of two distinct types of AIDS-associated non-Hodgkin lymphoma. AB - Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features. PMID- 2265115 TI - Studies on the megakaryocytes of a patient with the Bernard-Soulier syndrome. AB - We have used monoclonal antibodies AP-1 (anti-GP Ib alpha). AP-2 (anti-GP IIb IIIa) and FMC 25 (anti-GP IX) in immunofluorescence and immunocytochemical studies on megakaryocytes (MK) isolated from a Bernard-Soulier syndrome (BSS) patient whose giant platelets were characteristically deficient in GP Ib-IX complexes. Electron microscopy showed that the patient's MK were similar in size to normal MK. However, a striking feature was the variable and intermittent nature of the demarcation membrane system which was often vacuolar in appearance. Permeabilized mature MK from normal individuals were strongly positive with AP-2, AP-1 and FMC 25. Those from the BSS patient were normal for AP-2, negative for AP 1 but weakly positive with FMC 25. Binding of the monoclonal antibodies to the patient's platelets was evaluated using flow cytometry. The results confirmed the absence of GP Ib alpha from the surface membranes, but showed the presence of small amounts of GP IX distributed throughout the platelet population. Our findings confirm that the membrane lesion in BSS is also to be found in MK and further show that the defect may affect differently individual constituents of the GP-Ib-IX complex. PMID- 2265116 TI - Irradiation of platelets with UV-B light exposes fibrinogen binding sites via an intracellular mechanism. AB - Previous studies have shown that ultraviolet irradiation (UVI) causes platelet aggregation. In the present study we exposed platelet suspensions to a relatively high dose of UV-B (8 J/cm2) under conditions comparable to those of UVI of platelet concentrates in order to obtain more insight into the UV-induced aggregation response and to evaluate the significance of this phenomenon for the clinical use of UV-irradiated platelet concentrates. This study provides evidence that UV-B induced aggregation is mediated by a Ca2(+)-dependent process of fibrinogen binding to an intact glycoprotein IIb-IIIa complex on platelet membranes. Although UV-induced platelet aggregation is independent of thromboxane A2 formation and ADP secretion, it requires metabolic energy, cytosolic Ca2+ and a low cyclic-AMP level. Thus, UV-B irradiation causes platelet aggregation by exposing fibrinogen binding sites via an intracellular mechanism. Since the amount of bound fibrinogen following UVI is relatively low (about 2,300 molecules platelet) and the binding remains reversible, its effect on platelet behaviour after transfusion may be minor. PMID- 2265117 TI - Serum immunoreactive erythropoietin during pregnancy and in the early postpartum. AB - We studied 209 women during normal pregnancy, at delivery, or in the early postpartum, to determine whether erythropoietin (EPO) response was appropriate for the degree of anaemia. Serum immunoreactive EPO was measured in 74 nonpregnant women, including 33 normal subjects (16.4 +/- 4.1 mU/ml) and 41 women with hypoplastic, haemolytic, dyserythropoietic, or iron-deficient anaemia. An inverse linear relationship (R = -0.88, P less than 0.0001) between log(EPO) and Hct was observed. Predicted EPO values were derived for each Hct and an O/P ratio of observed/predicted log(EPO) was calculated for each sample (1.00 +/- 0.10, range 0.80-1.20). Serum EPO levels (mU/ml) were significantly higher during pregnancy (30 +/- 16, n = 142), at delivery (31 +/- 16, n = 41), and on day 7 postpartum (37 +/- 35, n = 26) than in normal women (P less than 0.001). EPO levels increased steadily from 18 +/- 6 mU/ml in the first, to 26 +/- 14 mU/ml in the second, and to 35 +/- 18 mU/ml in the third trimester (P less than 0.0001). The O/P ratio was normal on day 7 postpartum (1.01 +/- 0.16), at delivery (1.03 +/- 0.16), and in the third trimester (0.96 +/- 0.15), but was significantly reduced in the first two trimesters (0.88 +/- 0.15, P less than 0.001). A significant negative correlation between log(EPO) and Hct was lacking in the first two trimesters, was present but with a reduced slope during the third trimester and at delivery, and was normal postpartum. We conclude that EPO response to anaemia is impaired in early pregnancy, recovers in late pregnancy, and normalizes rapidly in the postpartum. PMID- 2265118 TI - L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. AB - L1 was given to eight patients with beta-thalassaemia major who had previously been treated with deferoxamine (DF) for 4-10 years. The patients' ages ranged from 11 to 27 years. Serum ferritin values ranged from 1.3 to 11.5 x 10(3) micrograms/l. L1 was given twice daily at a daily dose of 55-80 mg/kg body weight and was continued for 10 months in two patients, 9 months in three, 7 months in two patients and 4 months in one patient. As previously observed with DF, each patient's urinary iron excretion (UIE) varied greatly from day to day. The mean UIE of the eight patients ranged from 11 to 49 mg/d (0.2-0.87 mmol/d) on subcutaneous DF and from 16 to 53 mg/d (0.28-0.95 mmol/d) on L1. Two patients excreted significantly more and one patient significantly less iron while on L1. If the UIE was calculated as mmol Fe/mmol creatinine there was no statistically significant difference. Serum ferritin values fluctuated widely in all, with a consistent downward trend in three, no change in four and an increase in one of two non-splenectomized patients. This patient's splenomegaly and need for transfusions continued to increase while on L1. No toxicities attributable to the drug were detected during the period of study and tolerance of the drug was excellent. PMID- 2265119 TI - Constitutive gene expression of interleukin-5 in Kimura's disease. PMID- 2265120 TI - Lennert's lymphoma: response to 2'-deoxycoformycin. PMID- 2265121 TI - High dose intravenous methotrexate and reversible focal neurological deficit. PMID- 2265122 TI - Long-term survival in acute leukemia in adults. PMID- 2265123 TI - Syngeneic bone marrow transplantation for aplastic anaemia. PMID- 2265124 TI - Glycosphingolipids that can regulate nerve growth and repair. PMID- 2265125 TI - Erythropoietin: regulation of erythropoiesis and clinical use. PMID- 2265126 TI - Multidrug resistance and chemosensitization: therapeutic implications for cancer chemotherapy. PMID- 2265127 TI - Peptides: chemistry, biology, and pharmacology. PMID- 2265128 TI - New approaches to vaccination. PMID- 2265129 TI - Autonomic dysreflexia--a nurse's challenge. AB - Autonomic Dysreflexia (AD) is a potentially life-threatening complication for spinal cord injured individuals. It is one of the most serious emergencies that can develop post trauma. AD provides a challenge to nurses. A basic understanding of the patho-physiology involved in AD is recommended and encouraged for those people who care for the spinal cord injured. The purpose of this paper is to provide a tool for nurses to identify, understand and manage an AD crisis using a step-by-step approach. PMID- 2265130 TI - Blepharospasm, hemifacial spasm and the nurse's role. AB - Blepharospasm and hemifacial spasm are involuntary movement disorders that affect the facial muscles. They are classified as cranial dystonias. Their cause is unknown and the underlying pathophysiology is poorly understood. Both dystonias are more common in women than in men. It is the middle-aged group that is most frequently affected. Because of their high visibility, these disorders may cause considerable distress and embarrassment. Affected persons are often mistakenly considered to have psychiatric problems. In addition, both dystonias may result in severe disability. For example, the person with untreated blepharospasm may experience social isolation and functional blindness. Recently, therapy in the form of botulinum toxin became available in larger centers. Repeated injections of the toxin usually relieves symptoms and enable patients to resume a former lifestyle. Neuroscience nurses who are knowledgeable about cranial dystonias and the resources that are currently available can retard progression of disability and help restore the individual's quality of life. Informed neuroscience nurses can also play an important role in case-finding, counselling and referral. Two examples are presented in order to highlight some of the complexities inherent in the diagnosis and treatment of each type of cranial dystonia and to further clarify the nurse's role. These examples are based on the personal and professional experience of the authors. PMID- 2265131 TI - A review of brainstem strokes. AB - Stroke is the fifth leading cause of death and a common serious neurological problem. The location of a presumed ischemic lesion can be inferred by relating the observed signs and symptoms to the functional anatomy of the cerebral vessels. It is essential to be able to determine whether a lesion lies in the distribution of either the carotid or the vertebrobasilar arterial systems. The focus of this paper will be limited to a discussion of strokes occurring within the distribution of the vertebrobasilar system. Although nursing does not make medical diagnoses, a clear understanding of the clinical presentation and potential problems will enhance the nurse's ability to develop a comprehensive plan of care for the patient. PMID- 2265132 TI - Introducing Mr. Mud--children's perceptions of the brain. AB - Children's media and language are full of references to the head and brain. The Scarecrow from the classic movie "The Wizard of Oz" is but one example. With these influences, how in actuality do children perceive their brain and its function? How does the child's perception of his brain impact the course of his hospitalization in terms of socialization to the hospital, anxiety and preoperative teaching needs? In this paper, case studies will be presented which illustrate the assessment and incorporation of school-age children's perceptions of the brain in the planning of individualized approaches to nursing care. Developmentally appropriate strategies which facilitate a positive health experience for the child newly diagnosed with a brain tumour will be described. Further implications for nursing practice and research will be discussed. PMID- 2265133 TI - Breast cancer: oncogenes and suppressor genes. PMID- 2265134 TI - Surgery for lung metastases of sarcomas. PMID- 2265135 TI - Empiric treatment of infection during granulocytopenia. AB - Results from clinical trials conducted over the past 15 years suggest the following: a) Early empiric therapy with broad-spectrum antibiotics directed against Gram-negative bacillary bacteremia is necessary in febrile granulocytopenic cancer patients; b) The level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; c) Most empiric antimicrobial regimens will require therapeutic modifications; these alterations are necessary and contribute to a high overall success rate; d) Only microbiologically documented infections and especially bacteremias are useful for comparison of initial response to antimicrobial regimens; e) The response rate of Gram-negative bacillary bacteremia is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen; emergence of resistance to some beta-lactam antibiotics is quite common and necessitates successive modifications of empiric regimens with time; f) The combination of an anti-pseudomonal beta-lactam with an aminoglycoside is recommended as the standard for empiric therapy in febrile granulocytopenic cancer patients, especially in those with severe and persistent granulocytopenia who are suspected of having Gram-negative bacillary bacteremia; less neutropenic and/or asymptomatic patients may do well with monotherapy; g) Gram-positive pathogens have become a common cause of bacteremia in granulocytopenic cancer patients; the response rate to empiric regimens may be suboptimal but the associated mortality is low; h) Patients with severe granulocytopenia and protracted fever whose blood cultures remain negative are at high risk for contracting fungal infections; in these patients, empiric antifungal agents are probably indicated. PMID- 2265136 TI - Results of salvage surgery for metastatic sarcomas. AB - Between January 1970 and December 1988, 105 consecutive patients underwent complete resection for lung metastases from sarcoma, 33 of them in the years from 1970 to 1983 and 72 between 1984 and 1988. In the latter period, new criteria consisting of early bilateral surgical staging and lung resection through median sternotomy were adopted for the management of lung metastases, in all patients with purely intrathoracic relapse. There was no operative mortality, follow-up was updated in August 1989, and actuarial survivals were calculated by the logrank method at 36 months from the time of first lung resection. During the second period, the overall actuarial survival at three years improved significantly (24% vs. 50%, P less than 0.02), notwithstanding the higher incidence of patients with unfavourable prognostic factors. The three-year survival was also significantly better in the subset of patients with a disease free interval less than or equal to 12 mos. and/or multiple pathological lesions (9% vs. 45%, P less than 0.05). Contralateral occult metastases were resected in 10 of 29 subjects who underwent sternotomy for monolateral clinical lesions. Of 26 patients with further intrapulmonary recurrence, 16 (62%) were amenable to re operation and eventual surgical rescue. These data suggest that median sternotomy and early management of occult contralateral disease may contribute to an improvement in the long-term survival of patients with metastatic sarcomas. On the other hand, it is possible that the effectiveness of salvage surgery is related to the higher activity and wider application of adjuvant and salvage chemotherapy. PMID- 2265137 TI - Epirubicin or epirubicin and vindesine in advanced breast cancer. A phase III study. AB - One hundred thirty-three evaluable patients with advanced breast cancer entered a randomized trial comparing epirubicin 60 mg/m2 with a combination of epirubicin 45 mg/m2 and vindesine 3 mg/m2 day 1 and 8 every 4 weeks. In all 10 premenopausal women an oophorectomy was performed. Seventy-five patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for advanced disease and 68 had received adjuvant chemotherapy (cyclophosphamide or CMF). Among evaluable patients (72 in the epirubicin group and 61 in the epirubicin + vindesine group) response rates were as follows: complete response--seven versus six; partial response--31 versus 22; no change--16 versus 17 (p greater than 0.40). Median time to disease progression was 6 months in both groups and median survival times were identical (12 months). Thrombocytopenia was less frequent in the epirubicin + vindesine group (p less than 0.01). In the epirubicin + vindesine group, mild to moderate peripheral neuropathy was observed in 40% of the patients. Congestive heart failure developed in one patient with a cumulative dose of epirubicin less than 1000 mg/m2 and in 7 of 15 patients who had greater than 1000 mg/m2. Four died of this cause. In conclusion, epirubicin is effective as a single agent for advanced breast cancer. The combination with vindesine does not increase its efficacy. PMID- 2265138 TI - Changes in cancer incidence in the Swiss Canton of Vaud, 1978-87. AB - Changes in age-standardized cancer registration rates in the Swiss Canton of Vaud (population 530,000) over the two five-year calendar periods 1978-82 and 1983-87 were analyzed. The incidence of occurrence at lung and other tobacco-related sites remained stable (or slightly decreased in males), but showed a substantial increase in females (approximately 40%, from 6.8 to 9.5/100,000 world standard, for lung alone). Other upward trends were observed for skin in both sexes (approaching 50% for melanoma in males), female breast (+8.0%, reaching 69.5/100,000), ovary and urinary tract neoplasms. In contrast, declines were observed not only for stomach and cervix, but also for intestine, gallbladder and endometrium. Consequently, overall total cancer incidence (excluding non melanomatous skin) declined by 1.1% in males, but increased by 2.7% in females, reaching values of 277.9 and 205.4/100,000, respectively, in 1983-87. The absence of any substantive trends in incidence for cancers of the prostate, testis, brain and multiple myeloma is of potential interest, and represents an important indicator of the uniformly high standard of monitoring by this cancer registration scheme. In a public health perspective, it is discouraging that most of the increases were restricted to cancer sites whose etiology has long been well defined, i.e., tobacco for females and sunshine or other sources of non ionising radiation, although it is reassuring to be able to document the levelling of tobacco-related cancer incidence in males. PMID- 2265139 TI - TCNU in adenocarcinoma of the lung: a phase II study with divided doses. AB - TCNU, a new water soluble nitrosourea, has in preclinical studies shown higher activity when given as divided doses compared with one day single treatment. Accordingly, 38 consecutive patients with non-resectable adenocarcinoma of the lung received TCNU 40 mg/m2 p.o. daily for three days every 4 weeks. The response rate among 37 evaluable patients was 14%, median response duration was 17 weeks (range 5-57+ weeks) and median survival 22 weeks (range 3-96+ weeks). Hematologic toxicity was pronounced, especially thrombocytopenia, and 57% of the patients had WHO grade 3 or 4 WBC or platelet count. Overall, dose reduction or delay of treatment due to hematologic toxicity was necessary in 66% of the patients. This, together with the limited activity, renders TCNU in the present dose and schedule unsuitable for further investigations in this disease entity. PMID- 2265140 TI - The role of CA 125 in the early diagnosis of progressive disease in ovarian cancer. AB - The role of CA 125 determination in diagnosing progression of ovarian cancer was evaluated in 98 patients of whom forty-nine had progressive disease. An elevated CA 125 level at the time of progression was found in 36 (73%) patients. In 31 (63%) patients CA 125 increase preceded clinical progression for a median time lag of 4.5 months (range 0.5-29.5 months). The combination of serum CA 125, gynecological and general physical examination detected progression in 45 (92%) patients. The additional contribution of second-look surgery, CTscan, chest X-ray and routine laboratory tests was minimal. PMID- 2265141 TI - 5-fluorouracil (5-FU) plus high dose folinic acid (FA): a modified scheme with reduced toxicity. PMID- 2265142 TI - Cerebral emboli in chronic intravascular coagulation detected by single photon emission computer tomography (SPECT) PMID- 2265143 TI - The decade of the retina. PMID- 2265144 TI - Visual telencephalon modulates directional selectivity of accessory optic neurons in pigeons. AB - The directional selectivity of units within the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) was studied before and after lesions of the visual telencephalon (visual Wulst) in urethane-anesthetized pigeons. In intact pigeons, most nBOR units preferred upward motion with a temporal component or downward motion with a nasal component. The ipsilateral and bilateral telencephalic lesions generated a dramatic reduction in the number of cells with optimal responses to upward motion. The overall distribution of preferred directions was still bimodal following ipsilateral or bilateral Wulst lesions, with most units showing best responses to a straight temporal or to downward nasal directions. The contralateral Wulst lesions produced, instead, a marked reduction in downward preferences. The nBOR units which were studied in these cases showed mainly upward-temporal and upward-nasal responses. These data suggest an involvement of the visual Wulst in the determination of the directional selectivity of nBOR neurons in the pigeon. Specifically, the responses of nBOR units to upward motion appeared to depend on the integrity of the telencephalic descending systems which impinge, in both direct and indirect ways, upon that AOS nucleus. Taken together with data for the mammalian AOS, the present results indicate that nonretinal afferents to AOS nuclei have an important role in the functional organization of that subcortical visual pathway. PMID- 2265145 TI - Effects of calcium ions on L-type horizontal cells in the isolated turtle retina. AB - A technique by which the retina can be isolated from the turtle eye is described. Scanning electron microscopy revealed morphological variability between preparations and also between regions of the same one. Large areas were often totally free of any pigment epithelial cells, yet contained a high proportion of photoreceptors with complete outer segments. However, adjacent regions may contain photoreceptors without outer segments or with fragmented ones. The physiological properties of the horizontal cells also demonstrated large variability between different preparations. In all cases, lowering calcium concentration from 2 mM to 0.1-0.5 mM depolarized the horizontal cells and augmented the amplitude of the maximum photoresponses. However, these effects were accompanied by changes in the photoresponse kinetics and by a reduction in the horizontal cell sensitivity to light. Moreover, prolonged exposure to low calcium induced permanent damage to the retina as was indicated by the reduction in the response amplitude after superfusion with 2 mM calcium solution had been resumed. The toxic effects of low calcium were most apparent when superfusion with 0.1-1.0 microM calcium concentration was performed. These solutions induced complex time-dependent effects on the resting potential of horizontal cells and on the amplitude and kinetics of the photoresponses. We conclude from these observations that the normal concentration of extracellular calcium in the turtle retina is in the 2 mM range. PMID- 2265146 TI - A physiological model of binocular rivalry. AB - This paper presents a modified reciprocal inhibition model for the temporal dynamics of binocular rivalry. The model is based on neurophysiological mechanisms and is derived from human psychophysical data. A simple reciprocal inhibition oscillator may be described with a set of four coupled differential equations with a neurophysiological interpretation. However, such a circuit does not account for some aspects of the temporal behavior of binocular rivalry, including the effects of contrast change on alternation rate and on the magnitudes of changes in duration of the suppressed and dominant phases. To better account for these phenomena, the equations and their stimulation are modified to include three new components: (1) presynaptic inhibition of the reciprocal inhibition by the input, (2) the motor delays that occur when a human observer tracks rivalry and (3) a minimum threshold for each neuron's state variable. The result is a much improved fit to psychophysically-obtained data on the temporal behavior of binocular rivalry. Finally, the model is incorporated into a larger model to suggest how rivalry might occur in a network that usually exhibits binocular fusion. PMID- 2265147 TI - Light absorbed by 575-cones trigger rod disc shedding in the frog retina. AB - Photoreceptors periodically shed light-sensitive membranes; rods at light onset, cones at night. The spectral characteristics of light required to initiate shedding by 502-rods were studied in the frog retina. After 24 h of white light, animals were dark primed for 1 h then presented with 1 h of nearly monochromatic light to induce the shedding response. The light delivered a total photon flux of 2.5 or 0.5 microE/m2s. Following conventional fixation and plastic embedding, 1 micron sections were examined with light microscopy. The number of photoreceptor tips (phagosomes) shed by 100 consecutive rods were counted and plotted as a function of wavelength. Bright light induced at least 15 phagosomes per 100 rods at all wavelengths tested, 420-640 nm, and this shedding was more than doubled with light from 540-600 nm. When the light was dimmed, there was no shedding response except for this 540-600 nm window. This shedding peak closely corresponds to the absorbance curve of the frog's 575-cone photopigment and implies that the 575-cone can drive rod shedding. The broad background effect further indicates that all photoreceptors have an input and suggests that a luminosity cell, such as the internal horizontal cell, may be involved. PMID- 2265148 TI - Role of the color-opponent and broad-band channels in vision. AB - The functions of the primate color-opponent and broad-band channels were assessed by examining the visual capacities of rhesus monkeys following selective lesions of parvocellular and magnocellular lateral geniculate nucleus, which respectively relay these two channels to the cortex. Parvocellular lesions impaired color vision, high spatial-frequency form vision, and fine stereopsis. Magnocellular lesions impaired high temporal-frequency flicker and motion perception but produced no deficits in stereopsis. Low spatial-frequency form vision, stereopsis, and brightness perception were unaffected by either lesion. Much as the rods and cones of the retina can be thought of as extending the range of vision in the intensity domain, we propose that the color-opponent channel extends visual capacities in the wavelength and spatial-frequency domains whereas the broad-band channel extends them in the temporal domain. PMID- 2265149 TI - Macaque vision after magnocellular lateral geniculate lesions. AB - Ibotenic-acid lesions of the magnocellular portion of the macaque lateral geniculate nucleus were used to examine the role of the M-cell pathway in spatio temporal contrast sensitivity. A lesion was placed in layer 1 of the lateral geniculate of each of two monkeys. Physiological mapping in one animal demonstrated that the visual-field locus of the lesion was on the horizontal meridian, approximately 6 deg in the temporal field. Visual thresholds were tested monocularly in the contralateral eye, and fixation locus was monitored with a scleral search coil to control the retinal location of the test target. Three threshold measures were clearly disrupted by the magnocellular lesions. Contrast sensitivity for a 1 cycle/deg grating that drifted at 10 Hz was reduced from about twofold greater than, to about the same as, that for 10-Hz counterphase modulated gratings. Sensitivity for a very low spatial frequency (Gaussian blob), 10-Hz flickering stimulus was reduced so severely that no threshold could be measured. In addition, flicker resolution was greatly reduced at lower modulation depths (0.22), but not at higher depths (1.0). Two of the measured thresholds were unaffected by the lesions. Contrast sensitivity for 2 cycle/deg stationary gratings remained intact, and little or no effect on sensitivity was found for 1 cycle/deg, 10-Hz counterphase modulated gratings. Together, these results suggest that the magnocellular pathway makes little contribution to visual sensitivity at low to moderate temporal frequencies. On the other hand, some contribution to detection sensitivity is evident at lower spatial and high temporal frequencies, especially for drifting stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265150 TI - Intact "biological motion" and "structure from motion" perception in a patient with impaired motion mechanisms: a case study. AB - A series of psychophysical tests examining early and later aspects of image motion processing were conducted in a patient with bilateral lesions involving the posterior visual pathways, affecting the lateral parietal-temporal-occipital cortex and the underlying white matter (as shown by magnetic resonance imaging studies and confirmed by neuro-ophthalmological and neuropsychological examinations). Visual acuity, form discrimination, color, and contrast sensitivity discrimination were normal whereas spatial localization, line bisection, depth, and binocular stereopsis were severely impaired. Performance on early motion tasks was very poor. These include seeing coherent motion in random noise (Newsome & Pare, 1988), speed discrimination, and seeing two-dimensional form from relative speed of motion. However, on higher-order motion tasks the patient was able to identify actions from the evolving pattern of dots placed at the joints of a human actor (Johansson, 1973) as well as discriminating three dimensional structure of a cylinder from motion in a dynamic random-dot field. The pattern of these results is at odds with the hypothesis that precise metrical comparison of early motion measurements is necessary for higher-order "structure from motion" tasks. PMID- 2265151 TI - A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. AB - An electrical potential recorded from the cornea, the a-wave of the ERG, is evaluated as a measure of human photoreceptor activity by comparing its behavior to a model derived from in vitro recordings from rod photoreceptors. The leading edge of the ERG exhibits both the linear and nonlinear behavior predicted by this model. The capability for recording the electrical activity of human photoreceptors in vivo opens new avenues for assessing normal and abnormal receptor activity in humans. Furthermore, the quantitative model of the receptor response can be used to isolate the inner retinal contribution, Granit's PII, to the gross ERG. Based on this analysis, the practice of using the trough-to-peak amplitude of the b-wave as a proxy for the amplitude of the inner nuclear layer activity is evaluated. PMID- 2265152 TI - Neuronal structure of the lacertilian parietal eye, I: A retrograde label and electron-microscopic study of the ganglion cells in the photoreceptor layer. AB - The cellular connectivity of the lacertilian parietal eye is not well understood. Because the intercellular connections establish the foundation for information processing, we have investigated cellular connectivity of one cell type in this simple vertebrate retina. We also developed an in vitro preparation to study the anatomy of the parietal eye visual system. Horseradish peroxidase transport in the in vitro preparation revealed a class of displaced ganglion cells occupying positions among the photoreceptors, in a location where the presence of interneurons had been suggested. Three-dimensional reconstruction at the electron microscopic level showed that the morphology and synaptic input of these displaced ganglion cells is different from that of the previously known ganglion cells. The displaced ganglion cells receive an average of about 13 ribbon synapses from photoreceptors. The ribbon input is equally distributed between the soma and dendritic arbor. Junctional membrane measurement and ethanolic phosphotungstic acid-staining provided evidence for the existence of non-ribbon synaptic contacts (synaptoid junctions). Displaced ganglion cells make about 20 synaptoid junctions, 65% of which are on the dendritic arbor. The morphology of the displaced ganglion cell is such that a significant measure of synaptic input to the dendritic arbor will be transmitted to the soma. PMID- 2265153 TI - Teflon epidural catheter placement for intermittent celiac plexus blockade and celiac plexus neurolytic blockade. AB - A 58-year-old with acute/chronic pancreatitis was treated with celiac plexus blockade. A percutaneous teflon catheter was placed for intermittent blockade and used for definitive neurolysis. There were no complications using this approach to celiac plexus blockade. PMID- 2265154 TI - Complications of retrobulbar and peribulbar blocks. PMID- 2265155 TI - An open study comparison of 0.5%, 0.75% and 1.0% ropivacaine, with epinephrine, in epidural anesthesia in patients undergoing urologic surgery. AB - Ropivacaine 0.5%, 0.75% and 1.0% with epinephrine 5 micrograms/ml was investigated in an open, multi-center study for lumbar epidural anesthesia in 46 patients undergoing urologic surgery. The onset time for analgesia to T12 was 5-7 minutes after the end of the ropivacaine injection. Maximum segmental levels of analgesia (T4-6) were not different between the groups. Complete motor blockade was obtained in 3/15, 7/15 and 10/15 patients in the 0.5%, 0.75% and 1.0% groups, respectively. Duration of analgesia at the T10 level was 2.5 hours in the 0.5% group, and increased to 4 hours in the 1.0% group. Analgesia was satisfactory for surgery in all patients except for 2/15 in each of the 0.5% and 0.75% groups and 1/15 in the 1.0% group. Hypotension was experienced by three, six and three patients in the 0.5%, 0.75% and 1.0% groups, respectively. Bradycardia was seen in two patients in the 0.5% group and one patient in the 1.0% group. Backache was experienced by seven patients (four in the 0.5%, two in the 0.75% and one in the 1.0% group). No late-occurring adverse experiences were observed. In conclusion, 0.5%, 0.75% and 1.0% ropivacaine with epinephrine provide adequate analgesia and motor blockade for urologic surgery. PMID- 2265156 TI - Somesthetic and electrophysiologic effects of topical 0.025% capsaicin in man. AB - As a topical agent, capsaicin reportedly blocks pain without otherwise impairing sensation. Ten subjects underwent blinded, multiple-dose application of topical 0.025% capsaicin or control emollient to skin test sites in order to evaluate capsaicin effectiveness and toxicity. Clinical changes in somesthetic perception of pinprick, heat and cold developed, but neurogenic flare responses were unchanged. Clinical and electrophysiologic measures of large fiber and autonomic function were unaffected by capsaicin. This study indicates that 0.025% capsaicin is a safe topical agent with demonstrable clinical effects on small fiber function but not on large fiber or autonomic function. PMID- 2265157 TI - The effects of two different volumes of 0.5% bupivacaine in a canine model of interpleural analgesia. AB - The effect of increasing interpleural injectate volume was determined in a chronic canine model. Changes in evoked potentials were used as a marker of nerve blockade. Electrodes were fastened to the right fifth, seventh and ninth ribs of adult dogs at distal (D), middle (M) and proximal (P) sites. Electrodes were also fastened to the ipsilateral laminae of the fifth (T5L), seventh (T7L) and ninth (T9L) thoracic vertebrae. Evoked potentials were recorded at each lamina after stimuli were applied to the corresponding distal, middle and proximal rib electrodes. Interpleural catheters were placed under direct vision during surgery. The effects of 10 ml and 20 ml of 0.5% bupivacaine were studied for each dog. Following 10 ml of 0.5% bupivacaine, intercostal nerve block was produced at T5 and T7, as evidenced by decreases in amplitude (range, 6-53% of control, p less than 0.05) and increases in latency (range, 108-122% of control, p less than 0.05) of evoked potentials recorded between laminae and distal or middle electrodes. No significant changes were seen in any potentials recorded over T9. After 20 ml of 0.5% bupivacaine, all T5 potentials were abolished. Significant decreases in amplitude (range, 22-36% of control, p less than 0.05) and increases in latency (range, 117-126% of control, p less than 0.05) were produced at all T7 rib sites. Except for the D-T7L comparison, all T5 and T7 changes produced by 20 ml of bupivacaine were greater (p less than 0.05) than those produced by 10 ml. Twenty milliliters of bupivacaine also produced decreases in amplitude (range, 41 51% of control at all sites, p less than 0.05) and increases in latency (115% at D-T9L, p less than 0.05) at T9 sites. Twenty milliliters of 0.5% bupivacaine produces intercostal nerve block that is more pronounced and widespread than that produced by 10 ml of bupivacaine. PMID- 2265158 TI - Effect of thoracic epidural bupivacaine 0.75% on somatosensory evoked potentials after dermatomal stimulation. AB - The effect of thoracic epidural bupivacaine 0.75%, 9 ml, on early (less than 500 ms) somatosensory evoked potentials (SEPs) during electrical stimulation of the T10 and L1 dermatomes was examined in ten patients. Spread of analgesia (pinprick) was T3.7 +/- 0.5 to L2.5 +/- 1 (mean +/- SEM). Peak-to-peak amplitudes of the T10 SEPs were reduced (p less than 0.05) while an insignificant reduction was found in L1 stimulated potentials. SEPs were abolished in four and two patients at the T10 and L1 levels, respectively. The latency of the early SEP components (0, P1-3, N1-3) increased (p less than 0.05) at T10 but was not significant at L1 except for N2 and N3. Sensory threshold increased significantly in both stimulation areas during blockade. In conclusion, thoracic epidural administration of 9 ml of bupivacaine 0.75% does not provide total afferent somatic blockade despite sensory analgesia to pinprick. PMID- 2265159 TI - Effects of an intravenously administered arrhythmogenic dose of bupivacaine at the nucleus tractus solitarius in the conscious rat. AB - This study was designed to further investigate the CNS-mediated cardiovascular toxicity of local anesthetics and to determine any effect of anesthesia on the firing rate of cells in the nucleus tractus solitarius (NTS) of conscious animals. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. A femoral artery and vein were cannulated. A 3-mm hole was then drilled for placement of a unidirectional microdrive. The animal was removed from the stereotactic instrument, and EKG electrodes, pressure transducer and the microdrive containing a 1-micron tungsten electrode were attached. Animals were then placed in a canvas sling for recovery from the anesthetic. Cells of the NTS were located and cell firing rate (CFR) was continuously recorded. None of the animals exhibited any sign of discomfort upon recovery from anesthesia. CFRs decreased from 19 +/- 13 to 4 +/- 4 impulses/second at 20 +/- 16 seconds after the IV injection of bupivacaine (p less than 0.01). Maximum decreases in blood pressures were 26 +/- 15% of control and occurred at 32 +/- 14 seconds after the injection of bupivacaine. The maximum decrease in heart rate was 38 +/- 16% and occurred at 13 +/- 10 seconds after the injection of bupivacaine. Maximum heart rate changes occurred significantly earlier than maximum decreases in CFR (p less than 0.01). On the other hand, maximum blood pressure changes occurred significantly later than maximum decreases in CFR (p less than 0.01). The data reported here demonstrate that conscious animals respond similarly to animals anesthetized with chloral hydrate with respect to the medullary effect of local anesthetics. PMID- 2265160 TI - Comparative effects of subarachnoid hyperbaric bupivacaine and tetracaine procaine for cesarean delivery. AB - Hyperbaric solutions of 0.75% bupivacaine (8.25% dextrose), and 1% tetracaine mixed with an equal volume of 10% procaine were compared in a double-blind study of 22 parturients undergoing elective cesarean delivery and spinal anesthesia. The onset of sensory anesthesia and motor block was similar in the two groups. The maximal level of sensory anesthesia to pinprick was significantly higher after the use of the tetracaine-procaine mixture. The adequacy of anesthesia was similar in both groups as indicated by the lack of differences with regard to anesthetic supplementation between the groups. However, a significantly shorter duration of sensory anesthesia and motor blockade occurred in the group in which bupivacaine was employed. The incidence of hypotension was higher in those patients receiving the tetracaine-procaine mixture as indicated by the use of significantly higher total doses of ephedrine to maintain baseline blood pressure in this group. No differences in Apgar scores or blood gases were noted between the two groups of patients. This study suggests that hyperbaric 0.75% bupivacaine offers certain advantages over hyperbaric tetracaine-procaine when used in equal volumes for spinal anesthesia cesarean delivery. PMID- 2265161 TI - Use of hyperbaric bupivacaine with epinephrine for spinal anesthesia in infants. AB - Previous studies have established the efficacy of spinal anesthesia in infants with hyperbaric lidocaine, hyperbaric tetracaine and isobaric and hyperbaric bupivacaine. Use of the commercially available hyperbaric spinal anesthesia solution of 0.75% bupivacaine in 8.25% dextrose has not heretofore been documented in this patient population. We present a series of 12 cases in which this hyperbaric bupivacaine solution with epinephrine was used for spinal anesthesia in children younger than 8 months of age. PMID- 2265162 TI - Evaluation of a new cutaneous topical anesthesia preparation. AB - Topical anesthetic agents are usually not effective on intact skin because of poor penetration. EMLA is a new topical anesthetic formulation consisting of a eutectic mixture of the local anesthetics lidocaine 5% and prilocaine 5%. We evaluated the ability of this preparation to prevent or ameliorate the pain associated with the percutaneous placement of large IV catheters. Under double blind randomized conditions, either EMLA or placebo was applied to the dorsum of both hands and an occlusive bandage then placed over each application site. The creams were placed 30, 45 or 60 minutes prior to IV cannulation. A 16-gauge catheter was inserted through each application area. Patients were asked to evaluate the relative degree of pain at each venous puncture site. The EMLA site was preferred when the formulation was applied for 45 to 60 minutes prior to cannula placement (p less than 0.01, confidence limits for the binomial distribution). Cusum analysis confirmed this minimal effective application time. The results indicate that EMLA is an effective cutaneous anesthetic formulation when applied with an occlusive bandage for a minimal time period of 45 minutes. PMID- 2265163 TI - Interpleural analgesia in the treatment of severe thoracic postherpetic neuralgia. AB - Effective, long-lasting pain relief was produced in 26 patients suffering from severe thoracic postherpetic neuralgia by intermittent administration of local anesthetics into the pleural space through a percutaneously placed interpleural catheter. The duration of treatment varied from seven to 21 days. During this period, 30 ml of 0.5% bupivacaine with epinephrine (5 micrograms/ml) were injected every 24 hours. The injections were continued for three days after the patients were pain free or had reached an analgesic plateau. All patients achieved good to excellent pain relief. During a follow-up period of five to 15 months, their level of pain has not increased from the level achieved at the end of the treatment program. PMID- 2265164 TI - Local anesthetic efficacy of ropivacaine (LEA 103) in ulnar nerve block. AB - Ropivacaine (LEA 103) is a new long-acting local anesthetic that in animal experiments has proved to be equally potent but less toxic than bupivacaine. In this controlled double-blind study in man, the dose-response relation of ropivacaine was examined in peripheral nerve block and its potency was compared to that of bupivacaine. Nerve functions during bilateral ulnar nerve block were monitored in 70 normal subjects by a computer-controlled method. Results indicate that plain ropivacaine is optimally effective at concentrations between 0.5% and 0.75%, where it reliably blocks nerve functions for about 8 hours. Its profile of action is uniform for the different fiber groups and resembles that of bupivacaine. Addition of epinephrine does not improve latency or duration of ropivacaine nerve block. Adverse effects attributable to ropivacaine have not been observed. PMID- 2265165 TI - Selective transsacral nerve root blocks. AB - This study compares the effectiveness and extent of spread of two different volumes, 1 ml and 2 ml, of a local anesthetic/radiopaque dye combination (referred to here as the injectate) in selective sacral nerve root blocks. With 1 ml of injectate, a selective sacral nerve root block was obtained in seven of nine patients, and with 2 ml of injectate, in eight of nine patients, as measured by urodynamic testing or scoring of pain relief. The three patients who did not have a successful block in this study were effectively blocked at another sacral nerve on a later date (outside of the study) when injected with 1 ml of injectate. The group that received 2 ml of injectate had significantly larger spread of injectate than the 1 ml group. One milliliter of injectate can produce a selective sacral nerve root block. Increasing the volume of injectate increases the spread and thus the possibility of involving other nerve roots. This could then cause difficulty in the interpretation of the results of the block. PMID- 2265166 TI - Preoperative percutaneous ilioinguinal and iliohypogastric nerve block with 0.5% bupivacaine for post-herniorrhaphy pain management in adults. AB - The safety, effectiveness and duration of a percutaneous ilioinguinal iliohypogastric nerve block with 10 ml 0.5% bupivacaine, as a method for postoperative analgesia, were studied prospectively in adult patients undergoing unilateral inguinal herniorrhaphy under spinal anesthesia. Group I (n = 20) blocked patients were compared with Group II (n = 25), non-blocked control patients. A blinded observer assessed pain scores and analgesic requirements after surgery. Group I patients had less pain at 3, 6, 24 and 48 hours after surgery and also required less analgesics during the first two postoperative days. This technique appears to be a simple and safe method for providing effective and long-lasting postoperative analgesia following inguinal hernia repair in adults. PMID- 2265167 TI - Distance from skin to the lumbar epidural space in an obstetric population. AB - The distance from skin to the epidural space was measured in 163 patients receiving epidural analgesia. The mean distance was found to be 4.78 cm, which correlated with other anatomic measurements. The presence of edema and the ethnic origin of the patients had significant effects on this distance. PMID- 2265168 TI - Hemodynamic monitoring in epidural blockade: cardiovascular effects of 20 ml 0.5% bupivacaine with and without epinephrine. AB - Twenty patients scheduled for elective urologic surgery received epidural anesthesia with 20 ml 0.5% bupivacaine. Ten patients received an epinephrine-free solution and ten patients received epinephrine 5 micrograms.ml-1 added to the local anesthetic solution. The mean maximum level of sensory blockade was not different between the two groups (T7 and T8). After epidural administration of 20 ml of either solution, the mean arterial blood pressure decreased significantly from pre-blockade values. After administration of 0.5% bupivacaine with epinephrine, cardiac output, stroke volume and end diastolic volume increased significantly from pre-blockade control values. These changes occurred within two to four minutes after injection of the local anesthetic solution and are caused by the systemic effects of epinephrine. After 15 minutes, the ejection fraction in the plain bupivacaine group decreased significantly from pre-blockade control values and the bupivacaine with epinephrine group. The differences in hemodynamic effects of the two solutions can be explained by the vasoactive effects of epinephrine and the cardiodepressive effects of bupivacaine. PMID- 2265169 TI - Effect of epidural and subarachnoid injections of a 10% butamben suspension. AB - Three groups of dogs were each given repeat epidural injections of a 10% butamben suspension. A fourth group received a single subarachnoid injection of the butamben suspension. All dogs were later sacrificed and the spinal cord, meninges and spinal nerves were examined. The dogs receiving the epidural injections had no pathology. Those dogs that received subarachnoid injections had adhesive arachnoiditis. None demonstrated any evidence of neurolysis. Two cancer patients who had each received multiple injections of a 10% butamben suspension for the successful treatment of cancer pain prior to their deaths had autopsies and the spinal cords, meninges and spinal nerves were examined. No significant pathology due to the butamben was noted. Epidural butamben does not appear to cause any local tissue damage provided that subarachnoid needle placement has been ruled out. Subarachnoid butamben should be avoided. PMID- 2265170 TI - Failure of an epinephrine test dose to elicit tachycardia after intravascular epidural catheter placement. AB - A 58-year-old woman who was not taking beta-adrenergic block medication had a lumbar epidural catheter placed intravascular unintentionally. Epinephrine 15 micrograms in 3 ml saline or 2% lidocaine caused an increase in blood pressure and a decrease in heart rate. Observation of the patient for other signs of intravascular injection besides an increase in heart rate is discussed. PMID- 2265171 TI - Gone with the wind--the fate of epidural air. PMID- 2265172 TI - pH adjustment of 0.5% bupivacaine. PMID- 2265173 TI - Comments on the problems associated with epidural test dosing. PMID- 2265174 TI - Familiarity with the literature. PMID- 2265175 TI - A possible preventive effect of low-dose fish oil on early delivery and pre eclampsia: indications from a 50-year-old controlled trial. AB - A preventive effect of dietary marine n-3 fatty acids on early delivery and toxaemia has recently been hypothesized. In only one published controlled trial fish oil has been given to pregnant women, namely in that conducted during 1938-9 in London by the People's League of Health with a dietary supplement containing vitamins, minerals, and halibut liver oil. Although it was of high quality and its findings are hitherto unexplained, neglect and misinterpretation of the trial seem to occur commonly in reviews. Of the 5644 women who were enrolled the 622 withdrawals were independent of treatment. Alternate allocation to treatment was used, producing two groups that were well balanced as to age and parity. The supplement was given from about week 20. The control group did not receive any supplement. Reductions of 20.4% (95% confidence interval 9-30%, P = 0.00083) and 31.5% (95% confidence interval 11-47%, P = 0.0047) were seen in odds of delivering before 40 weeks of gestation and pre-eclampsia respectively. No significant effects were seen on perinatal mortality, average birth weight, deliveries after 40 weeks, hypertension in the absence of oedema and proteinuria, duration of labour, sepsis or breast-feeding occurrence. Later controlled trials with vitamins or minerals given in the same amounts as in this trial have largely failed to show convincing effects as seen here. A controlled trial assessing the isolated effects of fish oil in pregnancy is warranted. PMID- 2265176 TI - Body composition of goat kids during sucking. Voluntary feed intake. AB - The body composition of thirty-eight Granadina goat kids was measured. Six animals were slaughtered at birth while the remainder were kept individually at an environmental temperature of 24 +/- 2 degrees and a relative humidity of 60 +/ 5%. They were given goat's milk or a milk-substitute at two planes of nutrition until 15 or 30 d of age and then slaughtered. The goat's milk and milk-substitute contained 260.4 and 222.0 g digestible protein/kg and 23.23 and 20.85 MJ metabolizable energy/kg respectively. Voluntary feed intake as metabolizable energy was a function of metabolic body-weight (kg W0.75), equivalent to 2.42 and 2.44 times the energy requirement for maintenance for goat's milk- and milk substitute-fed animals respectively. There was a high degree of correlation between the empty-body concentration of dry matter, fat and energy and empty-body weight (P less than 0.001) or animal age (P less than 0.001), and between body weight and animal age (P less than 0.001). The relationships between empty-body composition and empty-body-weight were independent of type of milk or plane of nutrition. In contrast relationships between empty-body composition or empty-body weight and animal age were affected by the type of milk and, over all, by the plane of nutrition. All these results show that in these animals any body-weight will have a similar composition, but it will be reached earlier or later depending on dietary regimen and always with the limitation of voluntary intake. PMID- 2265177 TI - The immediate effects of abrupt diet composition changes in young pigs. AB - Forty pigs (twenty males and twenty females) were weaned at 4 weeks of age into individual cages, and their weights and feed intakes measured daily. From weaning to 16 kg live weight they were given free access to a feed with either 134 (L) or 278 (H) g crude protein (nitrogen x 6.25)/kg fresh weight. During this period pigs on feed L grew at a slower rate and converted feed less efficiently than pigs on feed H. At 16 kg live weight they were introduced to a 6 d period of feeding when, on successive days, they were given feeds L, H, L, H, L and H (if previously fed on L) or feeds H, L, H, L, H and L (if previously fed on H). For pigs previously given access to feed L the live-weight gain was 1061 v. 575 g/d on the days when H or L was given; the feed intake was 1078 v. 1027 g/d respectively. For pigs previously given access to feed H, the live-weight gain was 655 v. 610 g/d and the feed intake 844 v. 1071 g/d on the days when H or L were given. The interactions between the feed given previously and the feed given for the 3 d of the subsequent 6 d period were highly significant for both live weight and feed intake. These rapid changes in feed intake and growth rate suggest that the metabolism of young pigs is extremely flexible, with a rapid rate of response to a change in the protein content of their feed. PMID- 2265178 TI - Energy and nitrogen intake, expenditure and retention at 20 degrees in growing fowl given diets with a wide range of energy and protein contents. AB - Heat production (HP) and the intake and retention of energy and nitrogen were measured at 20 degrees in growing female broiler fowl given diets with metabolizable energy (ME) contents ranging from 8 to 15 MJ/kg at each of two crude protein (nitrogen x 6.25; CP) contents (130 and 210 g/kg). ME intake was partially controlled by the birds, but increased by 30% over the range of dietary ME concentration. CP intake varied directly with dietary CP: ME ratio, indicating that control of energy intake took priority and that food intake did not increase in order to enhance amino acid intake on low-CP diets. Maintenance energy requirement and fasting HP were not affected by diet. Although the HP of fed birds was significantly affected by dietary energy source, there was no evidence for regulatory diet-induced thermogenesis as energy intake increased. Total energy retention doubled on the higher-energy diets as a result of increased intake and retention efficiency in the absence of any compensation by diet induced thermogenesis. The proportion of energy retained as fat was negatively correlated with dietary CP: ME ratio. It was concluded that the growing female broiler fowl responded to large differences in energy intake and dietary CP concentration not by changes in rate of energy dissipation as heat but by changes in the quantity of energy retained and in the partition of retained energy between body protein and body fat. PMID- 2265179 TI - The effect of fishmeal supplementation of a straw-based diet on growth and calorimetric efficiency of growth in heifers. AB - Thirty-two 160 kg dairy heifers were used to measure the effects of increasing dietary protein content on growth and heat production. A basal diet containing (g/kg) 550 sodium hydroxide-treated straw, 220 barley, 220 sugarbeet pulp and 10 urea was offered with 0, 76 and 152 g fishmeal/kg dry matter of the basal diet (F0, F1 and F2 levels respectively). The three diets were each given at two levels of feeding (low, L; high, H): 57.6 g/d per kg metabolic body-weight (W0.75) for the LFO diet and 74.7 g/d per kg W0.75 for the HFO diet. Apparent digestibility of the diets increased in response to the addition of fishmeal. Mean dry matter digestibility values were 0.67, 0.67, 0.69, 0.66, 0.68 and 0.69 and those for acid-detergent fibre digestibility were 0.60, 0.63, 0.66, 0.58, 0.60 and 0.65 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively. Nitrogen retention increased in response to both fishmeal and feeding level. Live-weight gains were 170, 296, 434 g/d for the LF0, LF1 and LF2 diets and 468, 651 and 710 g/d for the HF0, HF1 and HF2 diets respectively. There were significant effects of increasing the plane of feeding and the level of fishmeal in the diet on live weight gain. Dietary effects on live-weight gains were accompanied by increases in mean energy retention of 23, 45, 82, 94, 160 and 152 kJ/d per kg W0.75 for diets LF0, LF1, LF2, HF0, HF1 and HF2 respectively, but no definite evidence was obtained that dietary supplementation with fishmeal modified the efficiency of utilization of metabolizable energy for growth. PMID- 2265180 TI - Biotin supply by large bowel bacteria in minipigs: evidence from intracaecal avidin. AB - The influence of a change of colonic availability of biotin on biotin status was studied. This was done by inhibition of biotin absorption by intracaecal avidin infusion. Five adult minipigs with a permanent caecal 'T' cannula were fed on a semi-synthetic, biotin-deficient diet for 4 months. Following an 8-week adaptation period there were nine sequential 1-week infusion periods with or without oral lactulose or antibiotics. Avidin infusion during weeks 2, 5 and 8 amounted to 18 mg/d (13 U/mg). Plasma biotin concentrations were not changed by avidin infusions. There was a significant average 84% rise in faecal biotin excretion during the avidin periods. Urinary biotin output following avidin decreased by 21%. This is taken as evidence that biotin synthesized by colonic bacteria is available for host metabolism. A rough estimate shows that under basal conditions 1.7-17% of the metabolic allowance may be covered by this metabolic route. PMID- 2265181 TI - The effects of dietary ligands on zinc uptake at the porcine intestinal brush border membrane. AB - Intestinal brush-border-membrane vesicles were prepared from the porcine small bowel by magnesium precipitation and differential centrifugation, and were functionally intact. The influence of dietary ligands on 65Zn uptake was determined using a 65Zn concentration of 5 microM, an incubation time of 1 min and a reaction temperature of 27 degrees, with a rapid filtration technique. At this low Zn concentration the addition of an excess of folate, histidine or glucose had no effect on Zn uptake. Addition of picolinate, citrate and phytate to the incubation medium significantly reduced Zn uptake at all concentrations of ligand examined. Any inhibitory effects of folic acid in vivo may thus be due to a mucosal rather than lumen interaction. Those ligands inhibiting absorption may have done so through the formation of Zn-ligand complexes, which are either insoluble, or which reduce the binding of Zn to its mucosal receptor. This in vitro model of Zn absorption is useful for comparing the effects of potential Zn binding ligands in the diet. PMID- 2265182 TI - Comparison of growth, nitrogen metabolism and organ weights in piglets and rats fed on diets containing Phaseolus vulgaris beans. AB - The effects of lectins in the diet have been mainly studied in rats. An important question is whether results obtained in rats can be extrapolated to larger animals like the pig. Phaseolus vulgaris beans are rich in toxic lectins. Therefore a study was carried out to compare the effects of diets containing 200 g Phaseolus vulgaris beans (raw or toasted)/kg in rats and piglets. Live-weight gain, nitrogen digestibility and N balance were much lower in piglets than in rats fed on diets containing raw beans. Live-weight gain and N balance were slightly negative in the piglets. When toasted beans were given, live-weight gain and N balance values were reduced in piglets but hardly at all in rats. Giving raw beans caused hypertrophy of the pancreas in the rats but in piglets the weight of the pancreas was reduced. Spleen weight was depressed in the piglets but not in the rats. Weight of liver was not affected in either animal species. When toasted beans were given no effects on the weights of pancreas, spleen or liver were found in piglets or rats. It was concluded that the piglet is much more sensitive to antinutritional factors in the Phaseolus vulgaris bean than the rat. PMID- 2265183 TI - Effect of variable protein contents in diets containing Phaseolus vulgaris beans on performance, organ weights and blood variables in piglets, rats and chickens. AB - A comparison was made of the effects of antinutritional factors present in Phaseolus vulgaris on piglets, rats and chickens. Also the hypothesis of whether the negative effect on weight gain due to the inclusion of raw Phaseolus vulgaris in the diet can be attributed to an insufficient supply of amino acids was tested. Test diets containing 200 g raw Phaseolus beans/kg were balanced for digestible protein and amino acids; in one diet extra casein was incorporated. The main response criteria were live-weight gain and the weight of various organs including the intestine. Live-weight gain in piglets was markedly reduced during feeding 200 g raw Phaseolus vulgaris/kg in the diet, but not in rats and chickens. Addition of casein did not improve the weight gain of the piglets, indicating that a toxic factor was responsible for the reduced weight gain and not an insufficient supply of amino acids. The weights of the spleen and thymus were markedly reduced in the piglets when the diets with raw Phaseolus beans were given, but not in the rats and chickens. Additional supply of casein did not change this effect. Indications were found that when the supply of dietary protein is adequate there is no reduction in pancreas weight with raw Phaseolus beans as was observed in previous experiments. The weight of the intestine was increased in all three species due to feeding raw Phaseolus vulgaris. PMID- 2265184 TI - The influence of mild cold on human energy expenditure: is there a sex difference in the response? PMID- 2265185 TI - Dietary trans fatty acids and reproduction. PMID- 2265186 TI - The influence of gangliosides on the hydrophilic pore edge line tension and monolayer fusion of lipid membranes. AB - It is shown that inclusion of gangliosides into planar phospholipid bilayers leads to an essential suppression of their monolayer fusion. In contrast to phospholipid lysoforms, the gangliosides do not cause an associative decrease of the specific energy of the hydrophilic pore edge determined in the experiments on the electrical breakdown of membranes. This phenomenon depends on the effective size of the polar headgroup of the gangliosides. It is supposed that the effect of gangliosides on the parameters mentioned is based on the fact that they have large hydrated polar headgroups which create steric hindrances, which prevent (i) the membranes to come into contact during monolayer fusion; (ii) the gangliosides to take part in hydrophilic pore formation. PMID- 2265187 TI - Calmodulin-binding proteins in granule and plasma membranes from bovine chromaffin cells. AB - Calmodulin-binding proteins in chromaffin granule membrane and chromaffin cell plasma membranes have been investigated and compared. Chromaffin granules were purified by centrifugation over a 1.7 M sucrose layer. Plasma membranes were obtained in a highly purified form by differential and isopycnic centrifugation. Enzymatic determinations of 5'-nucleotidase, a generally accepted plasma membrane marker, showed a 40-50-fold enrichment as compared to the cell homogenate. Marker enzyme studies demonstrated only minimal contamination by other subcellular organelles. After solubilization with Triton X-100, calmodulin-binding proteins were isolated from chromaffin granule membranes and plasma membranes by affinity chromatography on a calmodulin/Sepharose 4B column. On two-dimensional polyacrylamide gelelectrophoresis a prominent protein (Mr = 65,000, pI ranging from 5.1 to 6) consisting of multiple spots, was present in the calmodulin binding fraction from chromaffin granule membranes as well as from plasma membranes. Besides this 65 kDa protein both fractions had at least four groups of proteins in common. Also, proteins typical for either preparation were observed. In the calmodulin-binding protein preparations from chromaffin granule membranes a prominent spot with Mr = 80,000 and a pH ranging from 5.0 to 5.7 was present. This protein was enzymatically and immunologically identified as dopamine-beta monooxygenase. PMID- 2265189 TI - The gating of human red cell Ca2(+)-activated K(+)-channels is strongly affected by the permeant cation species. AB - Using inside-out patches, the effect of various permeant cations on the gating behaviour of the human red cell Ca2(+)-activated K(+)-channel was examined. For symmetric solutions the dwell time histograms indicated two shut and two open states. Mean open times as well as the open-state probability were affected by the permeant cation species: Rb+ stabilised the channel in the open configuration, whereas NH4+ had a destabilising effect. Intermediate stability was obtained in K+ solutions. Bi-ionic experiments indicated that the gating was influenced by the ion species occupying the channel, rather than by ions bound to external modifier sites. PMID- 2265188 TI - Regeneration of bacteriorhodopsin in mixed micelles. AB - Regeneration of bacteriorhodopsin from bacterioopsin and all-trans-retinal was studied in a mixed micelle system consisting of dodecyl sulfate, CHAPS and a water-soluble phospholipid dihexanoylphosphatidylcholine (hex2-PhosChol). Regeneration to approximately 40,000 M-1.cm-1 extinction at 550 nm (epsilon 550) was obtained with either 2.3 mM or 6.5 mM CHAPS along with 6.9 mM dodecyl sulfate and 4.5 mM hex2-PhosChol in 0.16 M NaCl and 40 mM phosphate (pH 6.0). Without CHAPS, the regeneration in 4.5 mM Hex2-PhosChol gave epsilon 555 = 27,800; without PhosChol, the 1:3 CHAPS/dodecyl sulfate mixture gave epsilon 550 approximately 20,000; and without PhosChol the nearly equimolar CHAPS/dodecyl sulfate mixture gave epsilon 550 approximately 10,000. The composition of the mixed micelles was estimated from fluorescence spectroscopy using pyrene butyryl hydrazine. The molecular weight was estimated by molecular seive chromatography to be 87,100 for 2.3 mM CHAPS, 6.9 mM dodecyl sulfate and 0.67 mM hex2-PhosChol; and 83,200 for 7.0 mM CHAPS, 6.9 mM dodecyl sulfate, and 1.1 mM hex2-PhosChol. These results are consistent with the idea that at low concentrations of CHAPS and dodecyl sulfate, CHAPS organizes the dodecyl sulfate into disk shaped bilayer micelles that are favorable for bacterioopsin refolding. However, a high concentration of either detergent inhibits regeneration. Added hex2-PhosChol can overcome the inhibitory effects of high concentrations of either CHAPS or dodecyl sulfate. PMID- 2265190 TI - A simple test for the sidedness of binding of transport inhibitors. AB - A new method is described for determining the sidedness of action of nonpolar inhibitors that rapidly diffuse through the lipid bilayer and could therefore interact with the carrier on both sides of the membrane. Sidedness is deduced from the effect of the inhibitor on the flux ratio for the substrate (the ratio of the rates of exchange and net transport). The advantages of the method are that the experimental measurements are made after the inhibitor has equilibrated rather than in the brief period when it is present on only one side of the membrane, and that any reversible inhibitor can be tested, whether the inhibition mechanism is competitive, noncompetitive, uncompetitive, or mixed. PMID- 2265191 TI - Inhibition of choline transport in erythrocytes by n-alkanols. AB - The choline transport system of erythrocytes is reversibly inhibited by ethanol, n-butanol, n-hexanol, n-octanol, and n-decanol, but not by n-dodecanol. Each methylene group in the alkyl chain contributes 560 cal/mol to the free energy of binding at the inhibitory site. Inhibition results from the cooperative binding of two molecules of an alcohol, judging by the Hill coefficient n of 1.7-1.9. The mechanism of inhibition is noncompetitive, and the partition of the carrier between inward-facing and outward-facing forms is unaffected by the alcohols; it follows that the four main carrier forms, the inner and outer free carrier, and the inner and outer carrier-substrate complex, are equally susceptible to inhibition. Hexanol and decanol accelerate the reaction of N-ethylmaleimide with a thiol group in the inner carrier channel, but ethanol and butanol, at concentrations that inhibit transport by 70%, do not. The disproportionate effects on substrate transport and the N-ethylmaleimide reaction are most simply explained as the direct result of binding of alcohol molecules in different regions of the carrier, rather than as the indirect result of a disturbance in the structure of the lipid bilayer induced by the alcohols. PMID- 2265192 TI - Intestinal absorption of dipeptides and beta-lactam antibiotics. II. Purification of the binding protein for dipeptides and beta-lactam antibiotics from rabbit small intestinal brush border membranes. AB - By photoaffinity labeling of brush border membrane vesicles from rabbit small intestine with photoreactive derivatives of beta-lactam antibiotics and dipeptides, a binding protein for dipeptides and beta-lactam antibiotics with an apparent molecular weight of 127,000 was labeled. The labeled 127 kDa polypeptide could be solubilized with the non-ionic detergents Triton X-100, n-octyl glucoside or CHAPS. If the vesicles were solubilized prior to photoaffinity labeling, no clear incorporation of radioactivity into the 127 kDa polypeptide occurred indicating a loss of binding ability upon solubilization. By affinity chromatography of solubilized brush border membrane proteins on an agarose wheat germ lectin column, the binding protein for dipeptides and beta-lactam antibiotics of Mr 127,000 was retained on the column. With N-acetyl-D-glucosamine the photolabeled binding protein for beta-lactam antibiotics and dipeptides was eluted together with the brush border membrane-bound enzyme aminopeptidase N. Separation from aminopeptidase N and final purification was achieved by anion exchange chromatography on DEAE-sephacel. Polyclonal antibodies against the purified binding protein were raised in guinea pigs. The photolabeled 127 kDa protein could be precipitated from solubilized brush border membranes with these antibodies. Incubation of brush border membrane vesicles with antiserum prior to photoaffinity labeling significantly reduced the extent of labeling of the 127 kDa protein. Treatment of brush border membrane vesicles with antiserum significantly inhibited the efflux of the alpha-aminocephalosporin cephalexin from the brush border membrane vesicles compared to vesicles treated with preimmune serum. These studies indicate that the binding protein for dipeptides and beta-lactam antibiotics of apparent molecular weight 127,000 in the brush border membrane of rabbit small intestinal enterocytes is directly involved in the uptake process of small peptides and orally active beta-lactam antibiotics across the enterocyte brush border membrane. PMID- 2265193 TI - Glycosylation of the human erythrocyte glucose transporter is essential for glucose transport activity. AB - The human erythrocyte glucose transporter is a fully integrated membrane glycoprotein having only one N-linked carbohydrate chain on the extracellular part of the molecule. Several authors have suggested the involvement of the carbohydrate moiety in glucose transport, but not definitive results have been published to date. Using transport glycoproteins reconstituted in proteoliposomes, kinetic studies of zero-trans influx were performed before and after N-glycanase treatment of the proteoliposomes: this enzymatic treatment results in a 50% decrease of the Vmax. The orientation of transport glycoproteins in the lipid bilayer of liposomes was investigated and it appears that about half of the reconstituted transporter molecules are oriented properly. Finally, it could be concluded that the release of the carbohydrate moiety from the transport glycoproteins leads to the loss of their transport activity. PMID- 2265194 TI - Internalization of the lipophilic fluorescent probe trimethylamino diphenylhexatriene follows the endocytosis and recycling of the plasma membrane in cells. AB - The lipophilic fluorescent probe trimethylamino-diphenylhexatriene (TMA-DPH) has been shown previously to behave as a marker of plasma membrane in living cell systems, and it has therefore been widely used in membrane fluidity studies via fluorescence anisotropy measurements. However, progressive internalization of this probe in cells could lead to unsuitable interferences, when long incubations times were required. The mechanism of this internalization had not yet been elucidated. We present here fluorescence-intensity kinetic results and fluorescence micrographic data on L929 cells and on mouse bone-marrow macrophages, which allow us to identify the mechanism as fluid-phase pinocytosis: the probe remains associated with the plasma membrane throughout its internalization-recycling flow and it is finally concentrated in lysosomes. The study was facilitated by the partition equilibrium property of TMA-DPH between plasma membranes and the external aqueous medium, which allowed to immediately distinguish the internalized fraction of the probe from the peripheral labelling, by simply washing cells. This conclusion is confirmed by the features of the influence of temperature on TMA-DPH internalization. PMID- 2265195 TI - 31P- and 1H-NMR investigations of the effect of n-alcohols on the hydrolysis by phospholipase A2 of phospholipid vesicular membranes. AB - 31P- and 1H-NMR spectroscopy of small, unilamellar egg yolk phosphatidylcholine (PC) vesicles in the presence of the lanthanide ion Dy3+ have been used to study the effect of various n-alcohols on the permeability induced by the action of the enzyme phospholipase A2 (PLA2). The method allows the monitoring of the number of PC and lysoPC molecules in the outer and inner monolayers. The results indicate that the initial rate of hydrolysis of PC by PLA2 is increased by all the n alcohols but in a chain-length dependent manner and that the maximum rate occurs at n = 8 (octan-1-ol). The subsequent rate is dependent upon the rate of transbilayer lipid exchange (flip-flop) of PC molecules from the inner to the outer monolayer. The vesicles only become permeable to the Dy3+ ions when lysoPC is mobilised in the flip-flop process of exchange of lipid molecules between the two monolayers. The n-alcohols affect both the time taken to initiate flip-flop of inner monolayer PC and the subsequent rate of permeability to Dy3+. The n alcohols are seen to affect all the above rates in an identical chain-length dependent manner, indicating a common cause for all observations which we identify as the degree of clustering of the n-alcohol molecules in the bilayer. The results are discussed in terms of the chain-length dependent mechanism of n alcohol interactions with the membrane and the mechanism by which the vesicles become permeable to Dy3+ ions. PMID- 2265196 TI - Irreversible thermoinactivation of glucoamylase from Aspergillus niger and thermostabilization by chemical modification of carboxyl groups. AB - The incubation of glucoamylase from Aspergillus niger at 70 degrees C induced its rapid and irreversible inactivation. The covalent modifications of the protein structure involved in the thermoinactivation depended on the pH of the medium. We observed the formation of a low amount of disulfide-linked oligomers showing that disulfide exchange takes place at pH 5.5. Hydrolysis of peptide bonds at pH 3.5 and 4.5 was also detected. The chemical modification of carboxyl groups with a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) decreased the rate of appearance of low-molecular-weight peptides at pH 3.5 and 4.5 upon heating at 70 degrees C. However, the rate of inactivation at such pH values was not modified. Modification of carboxyl groups with EDC in the presence of ethylenediamine leading to the transformation of three carboxyl groups to amino groups increased the thermostability of the enzyme for temperatures above the temperature of compensation, Tc, which is 60 degrees C. PMID- 2265197 TI - The heterogeneity of the polymeric intracellular hemoglobin of Glycera dibranchiata and the cDNA-derived amino acid sequence of one component. AB - The erythrocytes of the marine polychaete Glycera dibranchiata contain a number of different, single-chain hemoglobins, some of which self-associate into a 'polymeric' fraction. An oligodeoxynucleotide probe was synthesized based on partial amino acid sequences determined by chemical methods, and used to screen a cDNA library constructed from the poly(A+)mRNA of Glycera erythrocytes (Simons, P.C. and Satterlee, J.D. (1989) Biochemistry 28, 8525-8530). The longest positive inserts found were sequenced using the dideoxy nucleotide chain termination method. One complete clone was obtained: clone 5A, 816 bases long, contained 59 bases of 5'-untranslated RNA, an open reading frame of 441 bases coding for 147 amino acids and a 3'-untranslated region of 316 bases. The derived amino acid sequence of Glycera globin P1 was in agreement with the partial amino acid sequences obtained by chemical methods. Three additional inserts obtained in the screening were also sequenced: the inferred amino acid sequences proved to be partial globin sequences which were different from each other and from the sequence of P1. Thus, the 'polymeric' fraction of the intracellular hemoglobin of Glycera probably consists of at least four different globin chains much like the 'monomeric' fraction. Comparison of the 'polymeric' sequence with the two known 'monomeric' sequences, M-II and M-IV, shows that they share 54 identical residues. At 74 positions, the identical residues in M-II and M-IV differ from the corresponding residue in P1, including at E-7, where P1 has a distal His, in contrast to Leu in M-II and M-IV. The alignment of Bashford et al. ((1987) J. Mol. Biol. 196, 199-216) and their templates were used to examine the principal differences between the two types of Glycera globin sequences. They appear to consist of uncommon surface amino acid residues at positions C6 (Phe vs. Ala), E10 (Val vs. Lys), E17 (Lys vs. Val), G1 (Arg vs. Lys), G10 (Met vs. Ala) and H5 (Arg vs. Lys). One or more of these residues could be responsible for the self association exhibited by the 'polymeric' Glycera globins. PMID- 2265198 TI - Radical intermediates in veratryl alcohol oxidation by ligninase. NMR evidence. AB - Proton nuclear magnetic resonance (NMR) spectra of veratryl alcohol (3,4 dimethoxybenzyl alcohol) were obtained during its oxidation by ligninase. It was observed that a substantial increase in the linewidths of the resonances occurred only in the presence of both the enzyme and hydrogen peroxide. Quenching the reaction by the addition of alkali immediately restored the normal linewidths of the resonances. Furthermore, inversion-recovery experiments showed a decrease in the longitudinal relaxation time of the substrate when the enzyme was actively turning over. Changes in both these NMR parameters are consistent with the generation of radical intermediates during the ligninase-catalysed oxidation of veratryl alcohol. PMID- 2265199 TI - Changes of polymerization and conformation of hemoglobin S induced by thiol reagents. AB - Thiol reagents, covalently bound to cysteine beta 93, either inhibit or facilitate the polymerization process of hemoglobin S. The progelling effect of parahydroxymercurybenzoate or 2,2'-dithiodipyridine contrasted with the increased oxygen affinity and the destabilization of the T state of Hb shown by functional and NMR studies. Thiol reagents increased the oxygen affinity of Hb from 30 to 1000%. Such variability was also observed in the reduction (up to 50%) of the alkaline Bohr effect. We show that the antigelling or progelling activity of thiol reagents does not depend solely on the concentration of molecules present in the deoxy T state but that specific effects of the reagent affects molecular interactions of the hemoglobin S polymerization process. PMID- 2265200 TI - Investigation of the properties of bovine heart creatine kinase cross-linked with dimethyl suberimidate. AB - Dimeric bovine heart creatine kinase (EC 2.7.3.2, ATP: creatine N phosphotransferase) has been cross-linked with the bifunctional reagent dimethyl suberimidate at several concentrations to yield modified enzyme with enhanced stability towards heat denaturation. The degree of thermal stability is dependent on the degree of cross-linking with optimal stabilization occurring when approx. half of all the available amino groups are covalently attached to dimethyl suberimidate. Accelerated storage studies were performed and the results used to predict the storage time of the native and modified enzyme at lower temperatures. The cross-linked derivative was predicted to have a longer shelf-life at 4 degrees C than the native enzyme. Modification caused a reduction in the specific activity of the enzyme. The pH profile was altered following cross-linking, but the Michaelis constants were not changed. The modified enzyme exhibited a marked resistance to the action of some denaturing agents. PMID- 2265201 TI - Causes of the decrease in fluorescence due to proteolysis of alpha-casein. AB - Fluorescence decrease in casein solutions induced by proteolytic enzymes is mainly due to cleavage of alpha-casein, and in particular to alpha S1-casein, which is quantitatively the main component of commercial casein. Treatment of alpha-casein with o-iodosobenzoic acid, diminished its intrinsic fluorescence considerably and abolished the decrease in fluorescence induced by proteolytic cleavage. The carboxyterminal Trp at position 199 in alpha S1-casein contributes approximately 30% to the overall effect, while the Trp at position 164 contributes about 70%. Treatment of alpha-casein with cyanogen bromide lowered the initial fluorescence of the preparation, but, in the resulting fragment, trypsin still diminished some of the residual fluorescence. The velocity of decrease in fluorescence correlates with the distance from the Trp in position 164 at which the peptide bond is broken. This effect seems to be rather unique for the caseins, but particularly for alpha S1-casein; this is due to the existence of a Trp that is in the vicinity of hydrophobic amino acids and which upon hydrolysis, becomes exposed to a more hydrophilic environment. PMID- 2265202 TI - Polymeric structure of human respiratory mucin: studies on two protein components released upon reduction of disulfide bonds. AB - A major mucus glycoprotein (mucin) was purified from the tracheobronchial secretions of an asthmatic patient. Upon SDS-composite gel electrophoresis, the purified native (non-reduced) mucin gave a single band. SDS-gel electrophoresis on 6% polyacrylamide gels showed the absence of low molecular mass protein contaminants. However, SDS-PAGE (6% gels) of the reduced mucin showed the presence of a major high molecular mass mucin component and two low molecular mass components of 118 and 70 kDa, respectively. The 118 and 70 kDa components were purified by preparative electroelution of the reduced mucin. These components were also separated from the reduced mucin by gel-permeation chromatography on a Superose 6 column. Chemical compositional analyses showed that the 118 kDa component was a glycoprotein while the 70 kDa component was non glycosylated. The effect of disulfide bond reduction on mucin structure and the hydrophobic probe binding properties of native and reduced mucin were studied using the fluorescent probe technique. Mansylphenylalanine was used as the fluorescent probe. The native mucin showed the presence of a large number of low affinity (KD approximately 10(-5) M) binding sites for the probe. On the other hand, reduced-alkylated mucin containing the 118 and 70 kDa components showed the presence of additional high-affinity (KD approximately 10(-6) M) binding sites as well as low-affinity binding sites for the probe. Reduced alkylated mucin devoid of the 118 and 70 kDa components showed the presence of only low-affinity binding sites. These observations suggest that the availability of high-affinity probe binding sites upon reduction of mucin disulfide bonds may be either due to binding of the probe to the released component(s) and/or due to noncovalent interaction of the released component(s) with the mucin causing a conformational change in the mucin structure. Thus, the 118 and 70 kDa components appear to be an integral part of the total polymeric structure of the human respiratory mucin. PMID- 2265203 TI - Chemical modification of xylanases: evidence for essential tryptophan and cysteine residues at the active site. AB - N-Bromosuccinimide (NBS) completely inactivated xylanases from Chainia and alkalophilic and thermophilic (AT) Bacillus with a concomittant decrease in absorption at 280 nm and with second-order rate constants of 10,500 and 5000 M 1.min-1, respectively at pH 6.0 and 25 degrees C. The kinetic analysis of inactivation indicated that one and three tryptophan residues were essential for the xylanase activity from Chainia and Bacillus, respectively. The xylanases were also inhibited by 2-hydroxy-5-nitrobenzyl bromide (HNBB). The modification of cysteine residues by p-hydroxymercurybenzoate (PHMB) and N-ethylmaleimide did not cause a loss in activity of the xylanase from Bacillus, whereas that from Chainia was completely inactivated. The kinetics of inactivation revealed the involvement of one cysteine residue for xylanase from Chainia with a second-order rate constant of 50,000 M-1.min-1. The PHMB-modified enzyme failed to show the presence of titrable -SH groups. Xylan afforded complete protection against inactivation by NBS, HNBB and PHMB, indicating the involvement of tryptophan and cysteine residues at the substrate-binding region of the enzyme. PMID- 2265204 TI - 1H-NMR study of the mechanism of assembly and equilibrium heme orientation of sperm whale myoglobin reconstituted with protohemin type-isomers. AB - The products of the incorporation of various protohemin type-isomers into the heme pocket of sperm whale myoglobin were investigated by 1H-NMR in the met-cyano complexes, both immediately after reconstitution as well as at equilibrium. The type-isomers studied include those involving all possible interchanges of the two substituents on a given pyrrole. The protohemin-III and -XIII isomers, with true 2-fold symmetry, yielded only homogeneous products. Protohemins-XI, -XIV both exhibited two species after reconstitution, with one disappearing with time. Protohemin-I was the only asymmetric hemin that failed to exhibit two isomers initially. The orientation of the hemin within the pocket was established by nuclear Overhauser detected dipolar connectivities among heme substituents and between heme substituents and assigned heme pocket residues. At equilibrium, the heme orientations were dominated by the asymmetric propionate rather than vinyl dispositions on the hemin, with a clear preference for placing a propionate at the 8- vs. 5-methyl position of native myoglobin. For protohemin-XI, the propionates were found in the unexpected positions of the 7-propionate and 2 vinyl groups of native myoglobin, indicating that propionates can occupy positions well within the hydrophobic interior. The alternate heme orientation for the metastable intermediates detected for protohemin-XI and -XIV involved rotational isomerism about the alpha,gamma-meso axes bisecting the vinyl positions, but these two axes are at right angles to each other in the protein matrix. The fact that protohemin-XIV, but not protohemin-I, exhibits a reversed orientation as a reconstitution intermediate provides direct evidence that vinyl contacts, as well as propionate links, modulate the relative stabilities of the initial encounter complexes between hemin and apomyoglobin. The heme cavity molecular/electronic structure was found largely unperturbed for the complexes of the various protohemin type-isomers. PMID- 2265205 TI - Organization of functional groups of liver bilitranslocase. AB - Bilitranslocase transport activity can be described as consisting of three functional fractions, which depend on two distinct classes of sulfhydryl groups, on the one hand, and on the guanido groups of arginine residues, on the other. Each fraction accounts for approx. 50% transport activity. The pattern of transport activity inhibition resulting from step-wise derivatization of these functional groups indicates that, in general, derivatization of arginine residues prevents that of one class of sulfhydryl groups and vice versa, indicating their close location in the protein. Nevertheless, under appropriate conditions, derivatization of both functional groups can be achieved; however, the inhibitory effect produced is not additive. Hence, these two fractions overlap functionally and are likely to belong to a common functional domain of the protein. On the contrary, the other class of sulfhydryl groups can be derivatized, regardless of the state of the arginine residues. PMID- 2265206 TI - Response of rat liver glutaminase to magnesium ion. AB - The activity of rat liver glutaminase from sedimented fractions of freeze-thawed mitochondria is strongly affected by variation in the Mg2+ concentration within the approximate physiological range of activators. A rise in the Mg2+ concentration stimulates glutaminase by increasing the apparent affinity of the enzyme for its positive modifier phosphate. With the addition of 4 mM Mg2+ the M0.5 for phosphate activation decreased from 18 to 9.5 mM at pH 7.1, 10 to 5.8 mM at pH 7.4 and 6.4 to 4.0 mM at pH 7.7. The result is an increase in the apparent affinity of the enzyme for glutamine. With the addition of 4 mM Mg2+ the S0.5 of glutaminase for glutamine decreased from 24 to 13 mM at pH 7.1, 14 to 9.6 mM at pH 7.4, and remained unchanged at 8.2 mM at pH 7.7. Since Mg2+ stimulates glutaminase, as does a rise in pH (Szweda, L.I. and Atkinson, D.E. (1989) J. Biol. Chem. 264, 15357-15360), by increasing the apparent affinity of the enzyme for phosphate, it reduces the inhibitory effect of a decrease in pH and/or phosphate concentration over a physiologically relevant range. PMID- 2265207 TI - Selective production of hybridoma cells: antigenic-based pre-selection of B lymphocytes for electrofusion with myeloma cells. AB - Methods for pre-selecting B lymphocytes were studied and investigated. First, biotinylated antigen was used for selecting B lymphocytes. These pre-selected B lymphocytes were then combined with biotinylated myeloma cells by adding streptavidin. The final formula of the selected B cell-myeloma cell was as follows: B cell-(antigen-biotin-strept-avidin-biotin)-myeloma cell. Then, this B cell-myeloma cell conjugate was fused by the pulsed electric field (PEF) method, which fused only those conjugated cells. The fusion efficiency obtained by this method was 3-15-times higher than that obtained by the non-specific poly(ethylene glycol) (PEG) fusion method. Second, avidin-antigen conjugate was used to select B lymphocytes. For this purpose, bifunctional cross-linkers such as N succinimidyl 3-(2-pyridyldithio) propionate (SPDP) and m-maleimidobenzoyl N hydroxysuccinimide (MBS) were chosen. Each reagent contains two heterofunctional groups which can make covalent bond with both Lys and Cys residues. Typical avidin-antigen conjugate is expressed as avidin-SPDP (or MBS)-antigen. Thus, final B cell-myeloma cell conjugate was B cell-antigen-SPDP (or MBS)-avidin biotin-myeloma cell. The yield of this procedure was of the order of 10(-2). Here, we suggest that the pre-selection of B lymphocytes by biotinylated antigen or avidin-antigen conjugate is a new method of obtaining selected hybridoma cells which produce specific monoclonal antibodies against the antigen used for selecting B lymphocytes. PMID- 2265208 TI - Internalization-sequestration and degradation of cholecystokinin (CCK) in tumoral rat pancreatic AR 4-2 J cells. AB - Cholecystokinin (CCK) receptors were investigated in the tumoral acinar cell line AR 4-2 J derived from rat pancreas, after preincubation with 20 nM dexamethasone. At steady state binding at 37 degrees C (i.e., after a 5 min incubation), less than 10% of the radioactivity of [125I]BH-CCK-9 (3-(4-hydroxy [125I]iodophenyl)propionyl (Thr34, Nle37) CCK(31-39)) could be washed away from intact cells with an ice-cold acidic medium, suggesting high and rapid internalization-sequestration of tracer. By contrast, more than 85% of the tracer dissociated rapidly after a similar acid wash from cell membranes prelabelled at steady state. In intact AR 4-2 J cells, internalization required neither energy nor the cytoskeleton framework. Tracer internalization was reversed partly but rapidly at 37 degrees C but slowly at 4 degrees C. In addition, two degradation pathways of the tracer were demonstrated, one intracellular and one extracellular. Intracellular degradation occurred at 37 degrees C but not at 20 degrees C and resulted in progressive intracellular accumulation of [125I]BH-Arg that corresponded, after 1 h at 37 degrees C, to 35% of the radioactivity specifically bound. This phenomenon was not inhibited by serine proteinase inhibitors and modestly only by monensin and chloroquine. Besides, tracer degradation at the external cell surface was still observable at 20 degrees C and yielded a peptide (probably [125I]BH-Arg-Asp-Tyr(SO3H)-Thr-Gly). This degradation pathway was partly inhibited by bacitracin and phosphoramidon while thiorphan, an inhibitor of endopeptidase EC 3.4.24.11, was without effect. PMID- 2265209 TI - Effect of streptokinase on prostacyclin synthesis and phospholipase activity in cultured pulmonary artery endothelial cells. AB - In this study, we examined the effects of streptokinase on arachidonic acid release and prostacyclin biosynthesis in cultured bovine pulmonary artery endothelial cells. When intact cells were incubated with streptokinase, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1-10,000 units/ml). Streptokinase also caused a marked release of arachidonic acid. It induced rapid phospholipid hydrolysis, resulting in the release of up to 15% of incorporated [3H]arachidonic acid into the medium. After the addition of streptokinase, degradation of phosphatidylcholine and phosphatidylethanolamine was observed and lysophosphatidylcholine and lysophosphatidylethanolamine were produced. We also observed a transient rise in diacylglycerol after the addition of streptokinase. To test for phospholipase C activity, the release of incorporated [3H]choline, [3H]inositol and [3H]ethanolamine into the culture medium was determined. The level of radioactive inositol showed an increase, but the changes in choline and ethanolamine were comparatively small. An increase in inositol was detectable within 1 min after streptokinase addition and peaked after 15 min. Inositol phosphate and inositol trisphosphate were released, and these releases were suppressed by the addition of neomycin (50 microM). These results suggest that streptokinase stimulates phospholipase A2 and C activity, and that prostacyclin biosynthesis is subsequently increased in cultured endothelial cells. PMID- 2265210 TI - GTP hydrolysis by transitional endoplasmic reticulum from rat liver inhibited by all-trans-retinol. AB - GTP hydrolysis by an endoplasmic reticulum fraction from rat liver enriched in part-rough, part-smooth transition elements was inhibited by all-trans-retinol half maximally at a concentration of about 10 micrograms/ml. Similar results were obtained with GTPase activity partially purified by ion-exchange (DE-52) chromatography. The inhibition was non-competitive and given by both retinol and retinaldehyde but not by retinoic acid or alpha-tocopheryl acetate. The hydrolysis of other nucleoside di- and triphosphates was much less affected by retinol. The activity was inhibited by detergents but at much higher concentrations than by retinol. The results suggest that enhancement of cell-free transfer from endoplasmic reticulum to Golgi apparatus by retinol observed previously at low concentrations of cytosol may be mediated through an interaction with GTP. PMID- 2265211 TI - Catabolism of geraniol by cell suspension cultures of Citrus limon. AB - The addition of geraniol to cell suspension cultures of Citrus limon resulted in the rapid formation of nerol, citronellol, geranic acid and citronellic acid. Concurrently, a transient accumulation of bound forms of branched chain fatty acids, and, with a few hours delay, of regular chain C2 to C12 fatty acids was elicited. A concerted action of combined alpha/beta-oxidation enzymes on the terpenic acids, followed by an enlarged acetyl CoA pool is suggested. Terpene catabolism in plants and in vitro plant cells is discussed. PMID- 2265212 TI - Zonal distribution of peroxisomal 3-oxoacyl-CoA thiolase mRNA in liver from rats treated with di-(2-ethylhexyl)phthalate. AB - Treatment of rats with di-(2-ethylhexyl)phthalate leads to a dramatic increase in peroxisomal 3-oxoacyl-CoA thiolase RNA, the concentration being higher in the pericentral than in periportal hepatocytes. These findings indicate that the production of peroxisomal thiolase and the zonal distribution of the enzyme are regulated at a pretranslational level. PMID- 2265213 TI - Phosphorylation of steroid hormone receptors. PMID- 2265214 TI - Alterations in vasopressin and angiotensin II receptors and responses during culture of rat liver cells. AB - Vasopressin and angiotensin II binding and responses were studied in hepatocytes in primary culture for 4 h and 24 h. After 24 h of culture, angiotensin II was completely ineffective in elevating cytosolic [Ca2+], whereas the maximum [Ca2+] response to vasopressin was decreased by 66% and the sensitivity to the hormone was decreased approx. 20-fold compared with values after 4 h of culture. The dissociation constant (KD) for vasopressin binding to the cells was not significantly changed during 24 h of culture, but the Bmax was decreased by 63% compared with 4 h of culture. There was also no change in the KD for angiotensin II binding from 4 h to 24 h, but the Bmax was decreased by 90%. After 24 h of culture, there was no change in the plasma membrane concentration of phosphatidylinositol 4,5-bisphosphate or in the basal cell concentration of inositol trisphosphate. However, the trisphosphate did not increase with 100 nM angiotensin II and the response to 100 nM vasopressin was reduced by 66% compared with that at 4 h. The effect of guanosine 5'-(3-O-thiol) triphosphate on the polyphosphoinositide phospholipase C activity of liver cell plasma membranes was also measured. There was no decrease in the degree of stimulation of the phospholipase by this nucleotide after 24 h of culture. It is concluded that the loss of vasopressin and angiotensin II responses in cultured liver cells is due in part to changes in receptors and also in their coupling to a guanine nucleotide binding protein. PMID- 2265215 TI - Neonatal hypoglycemia. AB - Neonatal hypoglycemia is particularly dangerous for the brain when it is symptomatic or/and recurrent. In order to avoid symptomatic hypoglycemia a compensatory production of ketone bodies is required since they are actively taken up by the neonatal brain. Recurrent hypoglycemia can be avoided by stimulation of neonatal gluconeogenesis which is limited by glucose infusion and/or insulin secretion. Lipid administration induces a hyperglycemic response which is explained by a stimulation of gluconeogenesis. It also results in ketogenesis which provides the compensatory factors of hypoglycemia and which seems to be linked to gluconeogenesis. We therefore suggest that the best way to prevent neonatal hypoglycemia is achieved by supplementing the neonate with lipids and especially medium chain triglycerides. PMID- 2265216 TI - Human neonatal hypocalcemia. AB - Hypocalcemia is commonly observed in the neonatal period and is usually transient from a few days to a few weeks. On only rare occasions is neonatal hypocalcemia permanent and secondary to congenital hypoparathyroidism caused by either isolated absence of parathyroid glands or in association with other malformations. Most cases of neonatal hypocalcemia fall into one of two clinical categories. Namely early neonatal hypocalcemia occurs in 24-48 h of life and it is usually observed in premature infants or infants of diabetic mothers. Late neonatal hypocalcemia is observed at the end of the first week of life. In addition of these two major categories, neonatal hypocalcemia may occur in association with hypomagnesemia. PMID- 2265217 TI - Metabolic adaptations to change of nutrition at birth. AB - Birth represents a dramatic change of nutrition from a fetal diet rich in carbohydrates and poor in fat to a neonatal diet rich in fat and poor in carbohydrates. Gluconeogenesis and ketogenesis are absent or very low in the fetal liver when the mother is correctly fed, and these metabolic pathways emerge after birth to reach adult values after 24 h. Gluconeogenesis increases rapidly in the liver of the newborn in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this metabolic pathway. The rise in plasma glucagon, the fall in plasma insulin and the resulting increase in liver cAMP which occur immediately after birth are the factors which induce the activation of liver PEPCK gene transcription. The appearance of ketogenesis is also controlled by the changes of plasma insulin and glucagon that increase the capacity for liver fatty acid oxidation by decreasing lipogenesis and malonyl-CoA concentration, by reducing the sensitivity of carnitine palmitoyl-CoA I to the inhibitory influence of malonyl-CoA, and by activating hydroxymethylglutaryl-CoA synthase by desuccinylation. Once liver PEPCK has reached adult value, i.e. 12 h after birth, other factors are involved in the regulation of hepatic gluconeogenesis. Indeed, the supply of gluconeogenic substrates and of free fatty acid is of crucial importance to support a high rate of gluconeogenesis and to maintain normoglycemia in the newborn. In the liver, fatty acid oxidation provides essential co-factors (acetyl-CoA, NADH and ATP) to support gluconeogenesis, and in peripheral tissue fatty acid oxidation inhibits glucose oxidation and stimulates the production of gluconeogenic precursors (lactate, pyruvate and alanine). Similar mechanisms are operative in human newborn. A defective hepatic fatty acid oxidation is likely to explain the frequent hypoglycemia observed in small-for-date neonates. Administration of oral triglycerides is an efficient mean to prevent hypoglycemia in these newborns. PMID- 2265218 TI - Management of neonatal hyperbilirubinemia: rational use of phototherapy. AB - Phototherapy has been used to treat neonatal hyperbilirubinemia for more than three decades; however, it is only during the last ten years that an understanding of the mechanism of action of phototherapy has emerged. While visible light is known to photooxidize and photoisomerize bilirubin, recent data suggest that the formation of bilirubin structural isomers (lumirubin) is responsible for the decrement in serum bilirubin. This paper discusses current clinical recommendations for light dosage and wavelength and develops new guidelines based upon recent information of how light effects a reduction in the serum bilirubin concentration. PMID- 2265219 TI - Clinical approach to inherited metabolic disorders in neonates. AB - Most inborn errors of intermediary metabolism presenting in the neonatal period fall schematically into three clinical categories: (1) those which lead to a neurological distress 'intoxication type' with a symptom-free interval, vomiting, comas, hypertonia, abnormal movements and frequent humoral disturbances (organic acidaemias, congenital urea cycle defects); (2) those which lead to a neurological distress 'energy deficiency' type. Frequent symptoms in this group include hyperlactacidaemia, severe hypotonia, cardiomyopathy, failure to thrive and malformations (congenital lactic acidaemias, fatty acid oxidation defects, peroxysomal disorders); (3) those which present evidence of liver dysfunction and hepatomegaly (glycogenesis, neoglucogenesis defects, galactosaemia, fructosaemia, tyrosinaemia type I). According to these three major clinical presentations and according to the proper use of few screening tests (blood gases, glucose, ammonia, lactic acid, electrolytes, acetest), we propose a method of diagnosis which groups these children into five schematical syndromes: type I MSUD; type II organic acidaemias; type III; congenital lactic acidosis; type IVa, urea cycle defects; type IVb, non-ketotic hyperglycinaemia, sulfite oxidase deficiency, peroxisomal disorders; type V liver dysfunctions. Once the above classification has been made, sophisticated and specific investigations can be planned (amino acid chromatography, organic acid chromatography, enzymatic studies, etc). PMID- 2265220 TI - Mitochondrial defects of brain and muscle. AB - The brain and muscle are particularly vulnerable to mitochondrial defects as are the heart, kidney and liver. This hierarchy of organ involvement is reflected in the clinical signs and symptoms associated with these diverse encephalomyopathic syndromes. The biochemical correlates involve pyruvate metabolism, the citric acid cycle and the respiratory chain. Lactic acidosis is the metabolic signature in these diseases although not present in all syndromes, witness Leber hereditary optic neuropathy. Ragged-red fibers are equally distinctive in biopsied skeletal muscle but are present only with biochemical defects involving the respiratory chain. Defects of pyruvate metabolism and the citric acid cycle are inherited as autosomal or x-linked Mendelian traits. Respiratory chain defects may be inherited as Mendelian or maternal (non-Mendelian) traits. All mitochondria of the progeny are inherited from the mother; and all 13 polypeptides encoded by the mitochondrial genome are located in the respiratory chain (complexes I, III, IV and V). These biological principles are helpful in understanding the clinical syndromes and patterns of inheritance associated with the mitochondrial myopathies and encephalomyopathies. PMID- 2265222 TI - Carnitine supplementation in soy-based formula-fed infants. AB - Gradual increase of carnitine in plasma, tissues and urine after birth is a normal response of breast-fed infants and those receiving carnitine-containing formulas. Marked reduction of carnitine and acylcarnitines was noted in infants given diets not containing carnitine. These differences prompted the evaluation of the rationale for adding carnitine into soy-based formulas. In healthy term infants the lack of dietary carnitine did not induce deficiency symptoms but reduced the uptake of fatty acids for beta-oxidation. The cumulative effect of various metabolic disorders and carnitine deficient diets may culminate to carnitine deficiency. PMID- 2265221 TI - Sudden infant death syndrome and inherited disorders of fatty acid beta oxidation. AB - Evidence that inherited disorders of mitochondrial fatty acid beta-oxidation can cause sudden infant death syndrome (SIDS) comes from case reports, systematic autopsy studies, and family studies. Family studies are important when no pediatric autopsy has been done, which is still frequent. After reviewing the fatty acid beta-oxidation, and its pathophysiology, we present the results of our metabolic study on 189 siblings of SIDS victims, and on 84 'near-miss' infants. We have found evidence for a disorder of fat oxidation in 28 (15%) infants in the first group, and in 14 (17%) infants in the second group. Diagnosing and treating such disorders early in infancy may prevent some cases of SIDS to occur. PMID- 2265223 TI - Carnitine supplementation in the premature. AB - In higher organisms the carnitine acyltransferases reversibly esterify carnitine which is a primary role of carnitine. With this function it is involved in the beta-oxidation of long-chain fatty acids and in the regulation of CoASH/acyl-CoA ratio in the intracellular compartments. In the intrauterine life there is an increase in stores of carnitine. Many evidences show, that in this growth rate a determinant factor is the materno-fetal transport of carnitine. After interruption of this materno-fetal unit the premature infant depends on exogenous intake. In absence of the exogenous intake due to carnitine free nutrition the tissue carnitine reserves decline in preterm infants. Human milk and many formulas contain carnitine. In carnitine deficiency (insufficiency) syndromes besides of the impairment of oxidation of long chain fatty acids, depending on the degree of carnitine depletion, possible development of multiple deterioration of intracellular processes has been suggested. Impairment of lipid metabolism in preterm infants maintained on carnitine-free feeding regimens seems to be established, in turn, numerous supplemental works suggest a rationale for prevention of decrease of body reserves. PMID- 2265224 TI - Mechanisms for the control of gene activity during development. PMID- 2265225 TI - Bicyclic peptides: solid state conformation of cyclo(Glu-Leu- Pro-Gly-Lys-Leu-Pro Gly)cyclo(1gamma-5epsilon)Gly. PMID- 2265226 TI - A study of model energetics and conformational properties of polynucleotide triplexes. AB - The formation of triple-stranded nucleic acid helices is studied by molecular mechanics and molecular dynamics calculations. Using standard TAT and CGG homopolymers, single, triple, and quintuple molecular replacements are made. Some of these replacements are expected to form Hoogsteen bonds and some are not. While the electrostatic and total energetic differences for base triplet mismatches were dependent on the electrostatic model chosen, clear trends in the local geometric distortions were apparent. Relationships between these model built strand geometries and chemical probe experiments are discussed. PMID- 2265227 TI - Hydrodynamic study of flexibility in immunoglobulin IgG1 using Brownian dynamics and the Monte Carlo simulations of a simple model. AB - A simple bead model is proposed for the antibody molecule immunoglobulin IgG1. The partial flexibility of the hinge is represented by a quadratic potential associated to the angles between arms. Conformational and hydrodynamic properties are calculated using Monte Carlo (rigid-body) and Brownian dynamics simulations. Comparison of experimental and calculated values for some overall properties allows the assignment of dimensions and other model parameters. The Brownian dynamics technique is used next to simulate a rotational correlation function that is comparable with the decay of fluorescence emission anisotropy. This is done with varying flexibility at the hinge. The longest relaxation time shows a threefold decrease when going from the rigid Y-shaped conformation to the completely flexible case. The calculations are in good agreement with the decay times observed for IgG1. A flexibility analysis of the latter indicates that a variability of +/- 55 degrees (standard deviation) in the angle between the Fab arms. PMID- 2265228 TI - Theory of acoustic mode vibrations of DNA fibers. AB - A previous model for acoustic mode vibrations of a DNA molecule in water is extended to the case of an array of many DNA molecules, as occurs in the fibers studied in most experimental work on DNA. The acoustic modes of this system are found to consist of coupled modes of water sound vibrations and DNA acoustic modes. This model is used to study the electrostatic coupling of acoustic vibrations to the relaxational modes of the orientational degrees of freedom of the water molecules. It is found that the long-range or macroscopic electric field generated by the acoustic mode vibrations of the water-DNA system gives too small a damping and frequency shift of the acoustic modes to account for the observations on DNA fibers. Therefore, the observed damping and frequency shifts are most likely due to either friction between the surrounding water and the vibrating DNA, or coupling to the water orientation degrees of freedom resulting from the short range (i.e., screened) Coulomb interaction. The latter explanation (which is most likely the correct one) implies that the relaxation time of the hydration shell water is longer than the observed relaxation time by a factor of the static dielectric constant of the hydration water. PMID- 2265229 TI - Structure of the hydration shells of oligo(dA-dT).oligo(dA-dT) and oligo(dA).oligo(dT) tracts in B-type conformation on the basis of Monte Carlo calculations. AB - Monte Carlo simulations [(N, V, T)-ensemble] were performed for the hydration shell of poly(dA-dT).poly(dA-dT) in canonical B form and for the hydration shell of poly(dA).poly(dT) in canonical B conformation and in a conformation with narrow minor groove, highly inclined bases, but with a nearly zero-inclined base pair plane (B' conformation). We introduced helical periodic boundary conditions with a rather small unit cell and a limited number of water molecules to reduce the dimensionality of the configuration space. The coordinates of local maxima of water density and the properties of one- and two-membered water bridges between polar groups of the DNA were obtained. The AT-alternating duplex hydration mirrors the dyad symmetry of polar group distribution. At the dApdT step, a water bridge between the two carbonyl oxygens O2 of thymines is formed as in the central base-pair step of Dickerson's dodecamer. In the major groove, 5-membered water chains along the tetranucleotide pattern d(TATA).d(TATA) are observed. The hydration geometry of poly(dA).poly(dT) in canonical B conformation is distinguished by autonomous primary hydration of the base-pair edges in both grooves. When this polymer adopts a conformation with highly inclined bases and narrow minor groove, the water density distribution in the minor groove is in excellent agreement with Dickerson's spine model. One local maximum per base pair of the first layer is located near the dyad axis between adjacent base pairs, and one local maximum per base pair in the second shell lies near the dyad axis of the base pair itself. The water bridge between the two strands formed within the first layer was observed with high probability. But the water molecules of the second layer do not have a statistically favored orientation necessary for bridging first layer waters. In the major groove, the hydration geometry of the (A.T) base-pair edge resembles the main features of the AT-pair hydration derived from other sequences for the canonical B form. The preference of the B' conformation for oligo(dA).oligo(dT) tracts may express the tendency to common hydration of base-pair edges of successive base pairs in the grooves of B-type DNA. The mean potential energy of hydration of canonical B-DNA was estimated to be -60 to -80 kJ/mole nucleotides in dependence on the (G.C) contents. Because of the small system size, this estimation is preliminary. PMID- 2265230 TI - Amide III frequencies for Ala-X peptides depend on the X amino acid size. AB - Raman spectra of series of aqueous solutions of peptides containing two amino acids, glycine-X, alanine-X, and serine-X, where X is an uncharged amino acid, show that the amide III band shifts systematically to lower frequencies as the side chain of the X amino acid becomes larger. The range of this shift is about 20 cm-1, starting at 1275 cm-1 for alanine-glycine and moving to 1251 cm-1 for alanine-tryptophan, with a correlation coefficient of 0.93 with the mass of the X amino acid side chain for 10 peptides. The amide I frequencies remain constant as the X amino acid is changed. This shift may result from a change in the average conformational preference of the peptide, a change in vibrational coupling of the amide III modes with the X amino acid side chain, a change in molecular force constants, or a combination of these. These results present a test for computational methods. PMID- 2265231 TI - Relation between calculated amide frequencies and solution structure in Ala-X peptides. AB - Computational techniques have been used to aid interpretation of observed systematic shifts in the amide III frequencies of Ala-X peptides. Optimized structures and frequencies have been calculated for Ala-X peptides using GAUSSIAN86/88 with the 4-31G basis, MOPAC, and normal mode methods based on empirical force fields. We observe the following: (1) Frequencies calculated using scaled GAUSSIAN86 force constants correlate well with the experimental results. (2) Structures of the Ala-X peptides optimized by GAUSSIAN show a clear trend toward lower values of the dihedral angle phi as the X side chain becomes larger, while structures optimized here using semiempirical and empirical force fields do not show trends. (3) Computational changes in peptide conformations from beta-sheet to alpha-helix produce large changes in both amide I and amide III frequencies that are inconsistent with the experimental results. (4) Computational changes in the dihedral angle phi of Ala-Ala produce a change in the amide III frequency consistent with the experimental results. (5) The experimental frequency shifts cannot be attributed directly to the effects of changing mass. PMID- 2265232 TI - Thermodynamics of polymolecular duplexes between phosphate-methylated DNA and natural DNA. AB - Phosphate-methylated (P.M.) DNA possesses a very high affinity for complementary natural DNA, as a result of the absence of interstrand electrostatic repulsions. In this study, a model system phosphate-methylated d[Cn] with natural d(Gk) (n less than k) is chosen for an investigation of the thermodynamic properties that determine duplex stability. The enthalpy change of a melting transition is shown to be considerably larger than is observed for corresponding natural DNA duplexes. It is found that delta Hn0 of GG/CC nearest neighbor pairwise interaction equals -15.6 kcal/mol, compared to -11.0 kcal/mol for the natural analog. The entropy change is strongly dependent on the length of the natural DNA strand and the number of phosphate-methylated DNA oligomers hybridized. The results are explained by means of a model in which a cooperative effect for subsequent hybridizations of phosphate-methylated DNA oligomers is assumed, thus giving additional stability. PMID- 2265233 TI - Condensation of DNA by trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles. AB - In vitro condensation of DNA by multivalent cations can provide useful insights into the physical factors governing folding and packaging of DNA in vivo. We have made a detailed study of hexammine cobalt (III) induced condensation of 2700 and 1350 base pair (bp) fragments of plasmid pUC12 DNA by electron microscopy and laser light scattering. The condensed DNA takes the form of toroids and rods. Both are present in all condensates, but the proportion of toroids is higher with the larger fragments. The intact, closed circular plasmid produces smaller particles than the linear fragments. The size of a particle is independent of DNA fragment length. Two hours after adding the condensing agent, a typical toroid is about 800 A in diameter; the outer radius (R1) is approximately 400 A, and the inner radius (R2) is approximately 140 A for both sets of fragments. These dimensions are relatively stable, but there is sufficient change in both R1 and R2 to produce approximately 50% increase in volume from 2 to 24 h. A typical rod at 2 h is about 1800 A long and 300 A wide. The distribution of rod lengths is similar to that of mean toroid circumferences pi (R1 + R2), and the distribution of rod widths is similar to that of toroidal widths (R1-R2). The 2700-bp fragments show a significantly higher ratio of toroids to rods than the 1350-bp fragments. Both types of particle are multimolecular. The average number of molecules/particle, calculated from the above dimensions, assuming hexagonally packed B-form DNA with a center-to-center spacing of 27 A, is 13 +/- 4 for condensates of 2700-bp fragments and 26 +/- 11 for those of 1350-bp fragments. Monomolecular condensates of much larger DNAs have similar dimensions, suggesting that size is governed primarily by the balance of attractive and repulsive intermolecular forces rather than by the entropic factors associated with incorporation of a number of small particles into a larger one. The similar dimensions and volumes of toroids and rods indicate that the free energy cost of continual bending in toroids, minus that gained by extra net attraction in a cyclic particle, is comparable to that of abrupt bending or kinking in rods. Although the condensed particles are multimeric, their distinct toroidal or rodlike shapes distinguish them from the random aggregates that would be generally expected from the multimolecular association of large, flexible polymers. PMID- 2265234 TI - Condensation of DNA by trivalent cations. 2. Effects of cation structure. AB - Electron microscopy is employed to examine DNA aggregates produced by three tripositively charged condensing agents. Spermidine, hexammine cobalt (III), and me8spermidine (in which the amine groups of spermidine are exhaustively methylated) all produce condensates. The predominant form of condensate observed is toroidal; however, me8spermidine produces a large fraction of rodlike condensates. Distributions of toroidal radii and estimated volumes suggest that the size of condensates depends on the condensing agent employed, its concentration, and the time elapsed after addition of condensing agent. While ligand charge seems to be the major factor in predicting condensing power, ligand structure influences the morphology and dimensions of the particles produced. The ability to form hydrogen bonds is not required to promote condensation, since me8spermidine has no NHs. There may be a kinetic barrier to condensation at low me8spermidine concentrations. The relative proportions of toroids and rods may depend on the energetic compensation between bending and binding in cyclic structures, or on rate-limiting formation of sharply bent or kinked regions in rods. PMID- 2265235 TI - Molecular topology and dimerization of recombinant bovine somatotropin. PMID- 2265236 TI - Pharmacokinetics of promazine: I. Disposition in patients with acute viral hepatitis B. AB - Concentrations of promazine in plasma, plasma water, red blood cells, and urine were measured after oral administration of the drug to six patients during and after apparent recovery from the acute phase of viral hepatitis B. None of the promazine pharmacokinetic parameters were significantly different during and after the acute phase; these parameters included clearance, free drug clearance, metabolic clearance, volume of distribution, distribution and elimination half life values, plasma protein binding, and per cent excreted in the urine. During the acute period of the illness, SGOP, SGPT, alkaline phosphatase, and total bilirubin were increased in all patients; they returned to within or near the upper limits or normal after recovery. Despite the unchanged promazine disposition, four out of six patients had more severe promazine side-effects, such as sedation, postural hypotension, and dizziness during the acute phase of the illness. This study suggests that promazine disposition was not significantly altered as a consequence of viral hepatitis. However, the pharmacodynamic effects of promazine were changed significantly. Care must be taken with patients who are taking promazine during the acute phase of viral hepatitis B. PMID- 2265237 TI - Bioavailability and cardiovascular safety of Dexatrim (phenylpropanolamine hydrochloride) from a controlled-release caplet. AB - The bioavailability and pharmacokinetics of phenylpropanolamine hydrochloride (PPA HCl) from a Dexatrim controlled-release (CR) caplet and solution was studied. Each subject (n = 12) received either a 75 mg PPA HCl CR caplet once daily or a 25 mg PPA HCl solution given three times a day. All subjects received the medication for 4 consecutive days. On Day 1, the mean +/- SEM, AUC, tmax, and Cmax values were 1651 +/- 127 ng x h ml-1, 4.5 +/- 0.26 h and 143 +/- 13.5 ng ml 1, respectively, for the CR caplet and 1716 +/- 90.3 ng x h ml-1, 1.25 +/- 0.08 h and 126 +/- 5.8 ng ml-1 for the solution, respectively. At steady state (Day 4), the mean +/- SEM, AUC, tmax, and Cmax values were 1832 +/- 101 ng x h ml-1, 4.17 +/- 0.17 h and 151 +/- 6.5 ng ml-1, respectively, for the CR caplet and 2014 +/- 116 ng x h ml-1, 1.33 +/- 0.09 h and 143 +/- 8.7 ng ml-1, respectively, for the solution. The data from Day 1 were fitted to an oral one compartment model with a first order absorption rate constant, kA, first order elimination rate constant, k and lag time. The mean +/- SEM, kA, elimination half-life and lag time for PPA HCl from the CR caplet were 0.488 +/- 0.182 ng h ml-1, 5.84 +/- 1.66 h and 0.394 +/- 0.224 h, respectively. The mean +/- SEM, kA, elimination half-life and lag time for PPA HCl from the solution were 2.87 +/- 1.51 ng x h ml-1, 3.73 +/- 1.21 h, and 0.325 +/- 0.101 h, respectively. The smaller apparent kA and longer elimination half-life for PPA HCl from the CR caplet is due to the slow release of PPA HCl, thereby slowing its absorption producing sustained plasma drug concentrations. Blood pressures (supine and sitting) and heart rates measured at the time of blood sampling after the administration of the PPA HCl dosage forms demonstrated no clinically significant relationship between cardiovascular response and PPA HCl plasma concentration. These data demonstrate the bioavailability and pharmacokinetics of PPA HCl from a CR caplet and an immediate release solution. PMID- 2265238 TI - Biopharmaceutical evaluation of carprofen following single intravenous, oral, and rectal doses in dogs. AB - Absorption and disposition characteristics of carprofen were compared in the dog after intravenous, oral, and rectal administrations. Rectal formulations included an aqueous solution and a suppository. Single doses of 100 mg carprofen were given in a cross-over design and plasma concentrations of unchanged drug were determined by HPLC. Plasma concentration-time profiles could be adequately described after intravenous and extravascular administrations by tri-and biexponential functions, respectively. After intravenous applications the basic disposition parameters could be determined: mean (+/- S.D.) elimination half-life was about 11.7 (+/- 3.1) h; volume of distribution ranged from 0.12 to 0.22 l kg 1 and total plasma clearance was about 0.017 +/- 0.003 l h kg-1. After oral dosing, carprofen was rapidly absorbed (time of maximum concentration: 0.83 +/- 0.61 h) and comparison with the intravenous solution indicated complete bioavailability. After rectal administration, the rate of absorption evaluated through tmax and calculation of mean absorption times was always slower than after oral dosing. Relative bioavailabilities of the drug from the suppository were about 20 per cent lower than from rectal solutions. No significant difference in rates of absorption of carprofen from rectal solution and suppository was seen; this allowed the conclusion that drug release from the semi solid dosage form was not the rate-limiting step in carprofen absorption from the suppository. From the present study, it is concluded that rectal administration of carprofen offers an alternative to the oral route of drug intake. PMID- 2265239 TI - The effect of UVB-induced erythema on the percutaneous absorption of minoxidil from an aqueous topical solution. PMID- 2265240 TI - Biology and clinical relevance of human natural killer cells. PMID- 2265241 TI - Induction of human monocyte to macrophage maturation in vitro by 1,25 dihydroxyvitamin D3. AB - Cells of the mononuclear phagocyte system arise from circulating blood monocytes (MO) that undergo further maturation on leaving the vasculature and migration into the various tissues and body cavities. This terminal differentiation step is also observed in vitro when blood MO are cultured in the presence of serum. Yet, the inducing signals present in serum are not defined. We have established primary cultures from elutriation-purified blood MO and found that the active metabolite of vitamin D3 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) could induce maturation of MO to macrophages (MAC) in the absence of any serum proteins. Cells were cultured for 7 days with AB-group serum or 1,25(OH)2D3, respectively, and MO maturation analyzed by morphology, functional activity, and the expression of lineage-restricted maturation-associated antigens (MAX.1, MAX.3). At an optimal concentration of 10(-8) mol/L, 1,25(OH)2D3 promoted the development of fully differentiated MAC whose phenotype and functional competence in terms of cytokine release (tumor necrosis factor alpha, interleukin-6, fibronectin, and lysozyme) was comparable with MAC grown in serum. In conclusion, our data may add to the immunoregulatory potential of 1,25(OH)2D3, which may play an essential role in the ontogeny of the mononuclear phagocyte system. PMID- 2265242 TI - Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. AB - Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras. PMID- 2265243 TI - Transforming growth factor beta downregulates interleukin-1 (IL-1)-induced IL-6 production by human monocytes. AB - We investigated the effects of transforming growth factor beta (TGF beta) on the induction by interleukin-1 beta (IL-1 beta) of IL-6 in human monocytes. We found that IL-1 beta induced IL-6 messenger RNA expression in elutriated monocytes and IL-6 secretion in the supernatant. TGF beta did not induce IL-6. In contrast, TGF beta added to the culture inhibited, in a dose-dependent manner, the induction of IL-6 by IL-1 at the level of messenger RNA and bioactivity. These results show that IL-1 beta is able to stimulate IL-6 production by monocytes, TGF beta, by inhibiting this effect, may play an important role in regulating the IL-1 mediated components of the inflammatory response. PMID- 2265244 TI - Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus. AB - The pathogenesis of the hematologic abnormalities commonly observed in patients with acquired immunodeficiency syndrome (AIDS) is incompletely understood. We report here that in vitro growth of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from six patients with AIDS was not significantly different from that of normal human immunodeficiency virus (HIV) seronegative donors: 25.3 +/- 5 CFU-GM per 5 x 10(4) low density marrow cells and 33.5 +/- 5 BFU-E were observed in AIDS patients versus 32.7 +/- 5 CFU-GM and 42.1 +/- 5 BFU-E in controls. Furthermore, no HIV-DNA in individual colonies (CFU-GM and BFU-E) could be detected using the polymerase chain reaction (PCR) technique, although HIV-1 DNA was detected in peripheral blood mononuclear cells from the same patients. Similarly, normal bone marrow cells exposed in vitro to different isolates of HIV or recombinant purified HIV-1 envelope glycoprotein (gp) 120 did not exhibit any difference in growth of CFU-GM or BFU-E as compared with mock exposed bone marrow cells. HIV-1 DNA could not be detected by the PCR technique in individual colonies derived from HIV exposed marrow. This study suggests that committed myeloid and erythroid progenitors from AIDS patients are responsive to hematopoietic growth factors in vitro and do not appear to contain HIV-1 DNA. Also, HIV or its envelope gp did not alter the growth of hematopoietic progenitor cells in vitro. No evidence of HIV infection of progenitor cells could be demonstrated. Impaired hematopoiesis in patients with AIDS may not be related to direct effects of HIV on committed progenitor cells. PMID- 2265245 TI - Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6. AB - We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL 3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice. Serum IL-6 assay by IL-6-dependent mouse hybridoma cell line MH-60.BSF2 showed high levels of the tested serum with a peak at 2.5 hours with no detection at 10 hours after the injection. Heated IL-1 beta caused an increase of neither IL-6 nor CSF activities. Our data suggest that the thrombocytosis induced by IL-1 beta is mediated by IL-6 or a combination of IL-6 and other cytokine(s), and that IL-6 may play a regulatory role in platelet production in vivo. PMID- 2265246 TI - The role of calpain in stimulus-response coupling: evidence that calpain mediates agonist-induced expression of procoagulant activity in platelets. AB - Although calpain (the Ca2(+)-dependent protease) is widely distributed, its function is poorly understood. One cell in which it becomes activated as a consequence of activation of the cell is the blood platelet. The aim of the present study was to determine whether activation of calpain was responsible for any of the responses of platelets to stimulation. Platelets were incubated with calpeptin, a membrane-penetrating inhibitor of calpain, before being exposed to an agonist. Concentrations of calpeptin that totally inhibited the agonist induced hydrolysis of actin-binding protein (ABP) by calpain had no effect on many other responses associated with platelet activation: phosphorylation of myosin light chain, phosphorylation of P47, platelet shape change, aggregation of platelets, secretion of granule contents, or retraction of fibrin clots. However, these concentrations of inhibitor decreased the agonist-induced generation of procoagulant activity (assayed as the ability of platelets to catalyze the conversion of prothrombin to thrombin in the presence of factor Va and factor Xa). When thrombin was the agonist, the amount of ABP that was hydrolyzed was small; only a small component of the total agonist-induced procoagulant activity was inhibited by calpeptin. When collagen was the agonist, more ABP was hydrolyzed and the amount of procoagulant activity generated was greater; calpeptin decreased the collagen-induced procoagulant activity to levels comparable with those induced by thrombin in the presence of the inhibitor. We suggest that there are at least two mechanisms by which procoagulant activity is generated on activated platelets and that the agonist-induced activation of calpain mediates one of these mechanisms. These results show that activation of calpain is a component of the stimulus-response pathway in platelets. PMID- 2265247 TI - Sulfation of von Willebrand factor. AB - von Willebrand factor (vWF) is a multimeric adhesive glycoprotein essential for normal hemostasis. We have discovered that cultured human umbilical vein endothelial cells incorporate inorganic sulfate into vWF. Following immunoisolation and analysis by polyacrylamide or agarose gel electrophoresis, metabolically labeled vWF was found to have incorporated [35S]-sulfate into all secreted multimer species. The time course of incorporation shows that sulfation occurs late in the biosynthesis of vWF, near the point at which multimerization occurs. Quantitative analysis suggests the presence, on average, of one molecule of sulfate per mature vWF subunit. Virtually all the detectable sulfate is released from the mature vWF subunit by treatment with endoglycosidases that remove asparagine-linked carbohydrates. Sulfated carbohydrate was localized first to the N-terminal half of the mature subunit (amino acids 1 through 1,365) by partial proteolytic digestion with protease V8; and subsequently to a smaller fragment within this region (amino acids 273 through 511) by sequential digestions with protease V8 and trypsin. Thus, the carbohydrate at asparagine 384 and/or 468 appears to be the site of sulfate modification. Sodium chlorate, an inhibitor of adenosine triphosphate-sulfurylase, blocks sulfation of vWF without affecting either the ability of vWF to assemble into high molecular weight multimers or the ability of vWF multimers to enter Weible-Palade bodies. The stability of vWF multimers in the presence of an endothelial cell monolayer also was unaffected by the sulfation state. Additionally, we have found that the cleaved propeptide of vWF is sulfated on asparagine-linked carbohydrate. PMID- 2265248 TI - Thrombin generation is not increased in the blood of hemophilia B patients after the infusion of a purified factor IX concentrate. AB - Prothrombin complex concentrates (PCC), licensed for the treatment of hemophilia B, are known to carry a significant risk of thromboembolic complications. Although the reasons for thrombogenicity are not completely understood, several manufacturers have developed purified factor IX concentrates that contain negligible amounts of the other vitamin K-dependent factors. To evaluate whether or not the infusion of such a factor IX concentrate is followed by lesser activation of the hemostatic system than by the infusion of a PCC, we performed a series of coagulation assays on 11 hemophilia B patients before and after the administration of these two types of concentrate using a randomized cross-over design. The levels of prothrombin fragment F1 + 2, a sensitive measure of the in vivo cleavage of prothrombin by factor Xa, was significantly increased in plasma after PCC, but not after factor IX concentrate. Plasma fibrinopeptide A, a sensitive index of the enzymatic activity of thrombin on fibrinogen, also increased significantly after PCC but not after factor IX concentrate. The fragment B beta 15-42, a sensitive index of the enzymatic action of plasmin on fibrin II, did not change after either concentrate. There were also no differences in less sensitive coagulation measurements, such as plasma fibrinogen, antithrombin III, and fibrin monomers, nor in indices of platelet activation, such as beta-thromboglobulin and platelet factor 4. These findings show that the infusion of a purified factor IX concentrate can result in substantially less activation of the coagulation cascade than may be seen with PCC. PMID- 2265249 TI - Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases. AB - The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment. PMID- 2265250 TI - Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells. AB - Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu 13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions. PMID- 2265251 TI - t(3;21)(q26;q22): a recurring chromosomal abnormality in therapy-related myelodysplastic syndrome and acute myeloid leukemia. AB - We have identified an identical reciprocal translocation between the long arms of chromosomes 3 and 21 with breakpoints at bands 3q26 and 21q22, [t(3;21)(q26;q22)], in the malignant cells from five adult patients with therapy related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Primary diagnoses were Hodgkin's disease in two patients and ovarian carcinoma, breast cancer, and polycythemia vera in one patient each. Patients had been treated with chemotherapy including an alkylating agent for their primary disease 1 to 18 years before the development of t-MDS or t-AML. We have not observed the t(3;21) in over 1,500 patients with a myelodysplastic syndrome or acute myeloid leukemia arising de novo or in over 1,000 patients with lymphoid malignancies. We have previously reported that the t(3;21) occurs in Philadelphia chromosome positive chronic myelogenous leukemia (CML). Thus, the t(3;21) appears to be limited to t-MDS/t-AML and CML, both of which represent malignant disorders of an early hematopoietic precursor cell. These results provide a new focus for the study of therapy-related leukemia at the molecular level. PMID- 2265252 TI - Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells. AB - The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM. In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells. This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures. In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients. Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL-6 responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone. Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro. PMID- 2265253 TI - Time-dependent alterations in the deformability of human neutrophils in response to chemotactic activation. AB - Transit times of individual human neutrophils through single capillary-sized pores were measured to determine the time-dependent changes in the mechanical behavior of the cells during activation by the chemotactic agent formyl-methionyl leucyl-phenylalanine (FMLP) and in response to cytochalasin B (CTB) and colchicine. FMLP elicited a two-phase response consisting of a rapid increase in cell stiffness, which peaked between 2 and 3 minutes, followed by a partial recovery of deformability to a level significantly above that of control after 5 minutes. The mechanical changes closely followed changes in F-actin content, although the peak in cell stiffness appeared to lag the F-actin response. Treatment with 3 mumols/L CTB produced a transient decrease in cell rigidity followed by a return to control level in 10 minutes, whereas treatment with 30 mumols/L CTB resulted in a sustained decrease in cell transit times to a level 60% of control. Addition of 3 mumols/L CTB to cells prestimulated with FMLP produced a rapid (1 to 2 minutes) cessation of changes in cellular deformability produced by the FMLP. Colchicine treatment did not decrease cell rigidity, but produced a delayed increase in F-actin content accompanied by increased stiffness of the cells. These results implicate actin as the major determinant of the mechanical behavior of the neutrophil, as measured by whole cell deformability tests. The significant changes in cell deformability that occur in response to fractional changes in F-actin content suggest that changes in the structure of the actin network occur during these processes. PMID- 2265254 TI - Immunochemical and electrophoretic analyses of phosphorylated native and recombinant neutrophil oxidase component p47-phox. AB - Human polymorphonuclear neutrophils (PMNs) possess a potent oxygen-dependent microbicidal system that depends on the activity of a stimulus-activated multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Patients with chronic granulomatous disease (CGD) lack activity of this oxidase and consequently suffer severe and frequent infections. Components of the oxidase include both membrane-bound factors (most notably, cytochrome b559, which is absent in the X-linked form of CGD) and at least two cytosolic factors, one or the other of which is absent in autosomal CGD. Patients with CGD, particularly the autosomal type, have defective phosphorylation of proteins in the 44 to 48 Kd range. A polyclonal antiserum (B-1) that recognizes cytosolic oxidase components of 47 and 67 Kd was used to identify phosphoproteins in a cell-free oxidase system. Two-dimensional gel electrophoresis showed the identity of the 47-Kd cytosolic protein (p47-phox) recognized by B-1 and the cationic 47-Kd protein that is phosphorylated in normal but not p47-phox-deficient CGD cytosol during activation of the NADPH-dependent oxidase. All full-length and C-terminal recombinant p47-phox proteins augmented the superoxide-generating capacity of the cell-free system and were phosphorylated when added to cytosol from normal subjects or from a patient with p47-deficient autosomal CGD. These studies provide compelling evidence that the 47-Kd cationic protein that is a substrate for phosphorylation during the activation of PMNs is, in fact, p47-phox, a cytosolic protein previously shown to be critical for normal activity of the NADPH-dependent oxidase of PMNs. PMID- 2265255 TI - Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg) AB - Hemoglobin (Hb) Suan-Dok (alpha 109Arg) is a rare alpha-globin structural mutation that is linked to an alpha-thalassemia (alpha-thal) determinant. When inherited in trans to an alpha-thal-1 mutation (-), it results in Hb H disease associated with low levels (9%) of the Suan-Dok Hb. The nature of the thalassemic defect associated with the alpha SD mutation has been investigated by structural and functional studies. Sequence analysis of the cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in an otherwise normal alpha 2-globin gene. When the alpha 2SD-globin gene was introduced into mouse erythroleukemia cells, the steady state alpha-globin messenger RNA (mRNA) level was equivalent to the alpha A-globin gene control. Although in vitro translation of a synthetic alpha 2SD-globin mRNA generated levels of alpha globin equivalent to alpha 2A globin mRNA at early time points, the ratio of alpha SD to alpha A globin decreased markedly at later time points. These data suggest that the thalassemic defect associated with the Suan-Dok mutation results from a significant instability of the alpha SD globin. PMID- 2265257 TI - Tumor necrosis factor alpha in human bone marrow recipients. PMID- 2265256 TI - bcr breakpoint and prognosis of chronic phase chronic myeloid leukemia. PMID- 2265258 TI - Dietary intervention as adjuvant therapy in breast cancer patients--a feasibility study. AB - To evaluate the feasibility of using a low-fat diet (i.e. 20-25% of energy (E%) as fat) as a component of adjuvant therapy for breast cancer patients, 240 females aged 50-65 years and operated for a stage I-II breast cancer were entered into a randomized study. The intervention group (n = 121) was to reduce dietary fat intake to 20-25 E% and to increase the intake of carbohydrates. Dietary counselling complemented other adjuvant treatments and the patients were followed for two years. No dietary advice was given to patients in the control group (n = 119). There was no significant difference between the groups in terms of base line nutrient intake except for higher energy intake in the control group (p less than 0.05). Only 52% of the patients in the intervention group followed through with the dietary regimen for two years, and 89% of the patients in the control group had a two-year follow-up. Energy intake decreased in both groups after two years, and the difference between the two groups remained (p less than 0.01). Total fat intake decreased from 36.2 E% to 22.2 E% after one year in the intervention group and remained at that level after two years. Total fat intake in the control group decreased by 3.6 E% after two years. The low compliance raises concern about the protocol design. The study nevertheless indicates that a long-term reduction of dietary fat intake can be implemented in breast cancer patients. PMID- 2265259 TI - Steroid hormone receptor levels and adjuvant tamoxifen in early breast cancer. Ten year results of the Naples (GUN) Study. AB - Ten year disease-free survival (DFS) results of the Naples randomized trial of adjuvant tamoxifen (TM), 30 mg per day for 2 years versus no therapy according to receptor levels, are reported. From Feb. 1, 1978, through Dec. 31, 1983, 308 pre- and postmenopausal patients with early breast cancer entered the trial. Estrogen receptor (ER) data were available on 239 (77.6%) patients, progesterone receptor (PgR) data on 194 (63.0%), and both receptor data on 181 (58.8%). ER and PgR were assayed by dextran-coated charcoal technique in a single laboratory. The effect of adjuvant TM was significantly related to ER and PgR concentration of the primary tumor. The greatest TM benefit on DFS was evident in patients with the highest levels of receptors. The interaction between the treatment effect and receptor concentration was found whether ER and PgR were considered separately or together. PMID- 2265260 TI - Menstrual status and breast cancer surgery. PMID- 2265262 TI - Effect of naphthalene on sodium active transport in the frog skin. PMID- 2265263 TI - Postnatal growth in rats prenatally exposed to cigarette smoke or carbon monoxide. PMID- 2265261 TI - Biological response modifiers in the management of patients with breast cancer. AB - Despite impressive progress in understanding the biology of breast cancer, mechanisms of host defense, and the pathophysiology of the metastatic process, this burgeoning fact bank has made little impact on the management of patients with breast cancer. There are many interesting ideas for improved diagnosis and therapy in various stages of development, but few have actually translated into improved survival of patients with breast cancer. Potentially useful biological agents include cytokines, monoclonal antibodies, immunotoxins, vaccines, and adoptive cellular therapies. Therapies targetting growth factor receptors and the cellular machinery required for metastasis may become useful, especially when used in combination with other cytotoxic agents. Colony-stimulating factors may allow a test of the hypothesis that augmented dose-intensity of cytotoxic chemotherapy will cure more patients. Though we are not yet sure precisely how to use all of these new tools, there can be little doubt that their application will make a significant impact on the management of patients with breast cancer and other malignancies in the next decade. PMID- 2265264 TI - Effects of methylmercury in vitro on methionine synthase activity in various rat tissues. PMID- 2265265 TI - Effect of glucocorticoids on metal retention in rats. PMID- 2265266 TI - Selective quantification of inorganic mercury in tissues of methylmercury-treated rats. PMID- 2265267 TI - Effects of northern bobwhite (Colinus virginianus) age and weight on results of the avian dietary toxicity test. PMID- 2265268 TI - Variable chlordane residues in soil surrounding house foundations in Louisiana. PMID- 2265269 TI - Transboundary metal pollution of the Columbia River (Franklin D. Roosevelt Lake). PMID- 2265270 TI - Levels of zinc, copper, and lead in wines from the area south of Seville. PMID- 2265271 TI - Lead contamination levels in roadside vegetation of Tripoli area, Libya. PMID- 2265272 TI - Development of an estuarine sediment burrowing bioassay for shipboard use. PMID- 2265273 TI - Toxicity of Nigerian crude oil and chemical dispersants to Barbus sp. and Clarias sp. PMID- 2265274 TI - Effect of sublethal doses of three pesticides on the ovary of a carp minnow Rasbora daniconius. PMID- 2265275 TI - Toxicity of nickel and nickel electroplating water to Chlorella pyrenoidosa. PMID- 2265276 TI - Effect of fluoride on acetylcholinesterase activity and oxygen consumption in a freshwater field crab, Barytelphusa guerini. PMID- 2265277 TI - Cytological abnormalities induced by mercury water pollutants on Allium cepa L. PMID- 2265278 TI - Tissue distribution of mercury and selenium in minnows, Phoxinus phoxinus. PMID- 2265279 TI - Hispanic drinking in the US: thinking in new directions. PMID- 2265280 TI - An evil trade. PMID- 2265281 TI - Journal interview 28. Conversation with Raj Rathod. PMID- 2265282 TI - The 'methadone by bus' project in Amsterdam. AB - One of the methadone programmes of the Amsterdam Municipal Health Service is the 'methadone by bus' project. Two mobile clinics cruise the city, stopping at six different locations daily. The liquid methadone is consumed on the spot and clean needles and condoms are available. This project is based on the principles of 'harm-reduction', i.e. if it is not (yet) possible to 'cure' a hard drug user, one should at least try to minimize the harm they cause to themselves and their environment. As soon as a client refrains from the use of illegal drugs, the client can 'graduate' to other methadone programmes with a higher threshold. To prevent double prescription, all Amsterdam methadone programmes participate in the central methadone registration. The Amsterdam Municipal Health Service has contact with over 50% of the drug users. The estimated number of hard drug users has remained stable over the last 5 years, whilst the average age of drug users has increased to 32 years. In the future, increasing the average dosage and the provision of injectable drug users will be discussed to assess their role in further harm reduction. PMID- 2265283 TI - Withdrawal symptoms and alcohol dependence. What animal work may tell. PMID- 2265284 TI - Withdrawal symptoms and alcohol dependence. One man's craving is another man's dependence. PMID- 2265285 TI - What happens to drug misusers? A medium-term follow-up of subjects new to treatment. AB - In a 2.5-5 year follow-up study of 150 drug misusers who were new to treatment at three London Drug Treatment agencies, a 77% follow-up rate was obtained. High rates of self-reported abstinence from opiates and other drugs were found. Some 37% of those followed-up were totally drug free at follow-up. Seventy-one per cent were living in the community and of those 73% were opiate free and 35% were totally drug free. Only 18% had injected in the 4 weeks prior to follow-up. Thirteen per cent were in prison and 12% were resident in a therapeutic community. Being told about the dangers of HIV had persuaded some people to give up using drugs. PMID- 2265286 TI - A follow-up study of Asian problem drinkers. AB - This is a follow-up study of 70 patients referred for treatment of drinking problems. At the end of 12 months, it was found that 60% remained in abstinence, 8.5% social drinking, 28.5% relapsed or defaulted and 3% died. A poor outcome was observed in patients between 20 and 39 years old as compared to those between 40 and 59 years old. Patients with SADQ scores of less than 20 had good outcomes. However, there was no significant difference between Indian and Chinese patients. Marital status and social class were not useful predictors of outcome. PMID- 2265288 TI - Correlates of alcoholic beverage preference: traits of persons who choose wine, liquor or beer. AB - We studied correlates of wine, hard liquor or beer preference among 53,172 white men and women in a Northern California prepaid health plan. Preference for a beverage type was reported by 51% of drinkers; 22% of persons with a preference reported exclusive use of the preferred beverage. Persons who prefer wine are likely to be women, temperate, young or middle-aged, non-smokers, better educated and free of symptoms or risk of illness. Persons who prefer liquor are likely to be men, heavier drinkers, middle-aged or older, less educated and afflicted with symptoms or risk factors for major illnesses. Persons who prefer beer are likely to be young men who are intermediate between wine and liquor preferrers for most traits. The traits of persons reporting exclusive use of a beverage type were similar. These data identify correlates of beverage choice which need to be controlled for in alcohol-health studies. PMID- 2265287 TI - Drinking, the construction of ethnic identity and social process in a Western Australian youth subculture. AB - This paper presents an anthropological analysis of the meaning of drinking for the male members of the Skinhead youth subculture in Perth, Western Australia. Perth Skinheads are an exported and modified form of the original English Skinhead subculture. Using participant observation as the primary research method, the style of drinking is analysed as one of the ways in which the members of this subculture express their English ethnicity and constitutive of the social processes which underpin the subculture. The article also explores the reasons why Perth Skinheads do not conform to a pattern of drinking in rounds held to be characteristic of some working class drinking groups. PMID- 2265289 TI - Are increases in treatment levels and Alcoholics Anonymous membership large enough to reduce liver cirrhosis rates? AB - Recent reductions in liver cirrhosis morbidity and mortality rates have been noted in many Western countries. We have previously observed that these declines are associated with increases in treatment for alcohol abuse over regions of Ontario, and increases in Alcoholics Anonymous (AA) membership over American states. One important question is whether the potential impact of treatment and AA membership increases could be large enough to have an impact on population cirrhosis rates. We explore this issue using estimates of the effects of treatment and AA membership, and of the likelihood of alcohol abusers developing cirrhosis, derived from the research literature. The results suggest that increases in treatment and AA membership could indeed have made important contributions to declines in cirrhosis mortality and morbidity in Ontario (1975 82) and the USA (1979-82). PMID- 2265290 TI - An analysis of the abstinence violation effect in a sample of illicit drug users. AB - Studies using samples of alcoholics and cigarette smokers show that the occurrence of the abstinence violation effect predicts the likelihood of a full blown relapse following an initial slip from voluntary abstinence. The present study investigated this process in a sample of 31 illicit drug users. The attributional styles of abstainers and relapsers were examined in addition to the types of initial slip situations for the relapse group. No significant differences were found in attributional styles, although relative to the relapse group there was a tendency for abstainers to score higher on internality and stability of attribution for negative events, but lower on globality. Both negative affect and interpersonal conflict, but not social pressure, were found to be important precipitants for relapse. Demographic differences between the groups are discussed in addition to the implications of the results for models of relapse, prediction of relapse and cognitive therapy in relapse prevention. PMID- 2265291 TI - Discordance of physiological and biochemical response to smoking and to psychological stress. AB - Both smoking and psychological stress produce marked effects upon cardiovascular function, and several studies have demonstrated that in combination they produce additive or potentiating effects. More recently, it has been reported that individuals strongly reactive to psychological stress are also strongly reactive to nicotine. In an attempt to replicate and extend those findings, we examined reactivity to smoking and competitive mental arithmetic across several physiological and biochemical variables. Despite stable responding across mental arithmetic trials, we were unable to demonstrate significant correlations between reactivity to smoking and to a psychological stressor. We further observed that anxiety level, when low, was a poor predictor of desire to smoke and of withdrawal, whereas higher anxiety levels were more tightly linked to these measures. These findings have implications for the identification of individuals at risk of cardiovascular disease as well as for the design of smoking treatment and relapse prevention programs. PMID- 2265292 TI - Children's purchases of single cigarettes: evidence for drug pushing? AB - The purchase of single cigarettes from shops by children aged 14 and 15, to whom all cigarette sales are illegal, was studied in a survey of 3513 teenagers attending nine state secondary schools in the Bristol area. Of those children who had tried smoking only once, 5% reported having at some time purchased a single cigarette from a shop. This percentage rose to 18% in current occasional smokers of less than 1 cigarette per week, and reached 52% in those smoking more than 6 cigarettes per week. There was no difference by sex or age, but some evidence of an association with family smoking habits and with social class, and wide variation between schools. In the school with the highest incidence, 80% of regular daily smokers had at some time bought single cigarettes from a shop, compared with 14% in the school with the lowest. Only 1% of children who smoked said that buying single cigarettes from shops was their usual way of getting cigarettes. Our results imply a cynical flouting of the law by many shopkeepers who are acting straightforwardly as drug pushers. PMID- 2265293 TI - Alcohol taxation: EC approximation and its UK effects. AB - The paper reviews the European Commission's (EC's) latest proposals for the approximation of indirect taxes on alcohol. In them, the Commission publicly and unequivocally accepts the connection between alcohol taxes and health. The paper compares the proposed target rates with existing alcohol taxes in the UK, and presents some simulated estimates of their effect on UK consumption. The estimates are preliminary, but are published now rather than risk delaying until the EC has taken irreversible decisions. They relate to 1988, the latest year for which simulations could be run, and suggest that, if the target rates had applied then in the UK, consumption per adult would have been more than two litres of pure alcohol higher than otherwise. The paper also reviews the objectives of a Single Internal Market in the EC and argues that indirect tax approximation is not necessary to achieve them. The current EC proposals are a serious threat to alcohol control policy in the UK, but are unnecessary to attaining the basic goals of a Single Internal Market and contain an open invitation for Member States to argue for national sovereignty, on health grounds, in choosing rates of alcohol excise duty. The paper suggests that this should be the UK argument in continuing discussions at the Community level. PMID- 2265294 TI - The Drug Advisory Service of England and Wales--the first 2 years. AB - An historical account is presented of the introduction and subsequent work of the Drug Advisory Service (DAS) of England and Wales since 1986. Data are presented from an analysis of the recommendations contained within the first 11 reports. The structural and operational strengths and weaknesses of the present approach are considered, and alternative approaches which might constitute constructive modifications or supplements to the present system are discussed. PMID- 2265295 TI - Poppy tea drinking in East Anglia. AB - Poppy tea drinking was a widespread traditional practice in the Fenlands of East Anglia during the nineteenth century. The subsequent social changes which led to greater integration of the area with the rest of the country may have contributed to a decline in the practice. In recent years poppy tea drinking has been revived within the illicit drug using community and a survey using a self-report questionnaire was carried out among patients attending the Cambridge Drug Dependency Unit. Forty-three patients admitted to drinking poppy tea, usually during the summer months and on an intermittent basis. The potency of the infusion varied and was unpredictable but in general was low. Although poisoning from herbicides and pesticides was seen as the main risk, it is in the main perceived by drug users as a harmless secondary activity existing alongside the more regular and more potent drugs of misuse. PMID- 2265296 TI - Buprenorphine abuse: report from India. AB - Buprenorphine has been stated a drug of low abuse potential and often used therapeutically in the management of opiate addicts. An analysis of 2 1/2 years' experience of opiate addiction cases at a de-addition clinic revealed its increasing rate of abuse, especially as a substitute for heroin. PMID- 2265297 TI - Characteristics of the Alcoholics Anonymous movement in Israel. PMID- 2265298 TI - Paediatric audiological medicine: policy and perspectives. PMID- 2265299 TI - The effect of stimulus level on click evoked oto-acoustic emissions and brainstem responses in neonates under intensive care. AB - Click evoked oto-acoustic emissions (EOAE) at a range of stimulus levels and the auditory brainstem response (ABR) threshold have been measured in 40 infants admitted to a neonatal intensive care unit (NICU). The stimulus levels at which the emissions were first observed had a similar mean value and distribution to those found in previous studies on normal newborns and young adult volunteers. The difference was in the proportion who had no detectable emissions, 16.7% as against 3.9% in the normal newborns and 2.6% in young adult volunteers. The distribution of thresholds for the ABR was again similar to those measured on normal newborns but 8.1% of the ears of the NICU infants had a threshold worse than 53 dBnHL compared with 0% for the normal newborns. A combined screening method starting with the click evoked oto-acoustic emission is proposed. A comparison of the mean ABR thresholds for those in whom an EOAE was recorded to those with no EOAE showed a group effect. The stimulus latency relationship of the NV peak showed too much variation between individual results to consider its use to define accurately the degree of conductive hearing loss. PMID- 2265300 TI - The advantages and disadvantages of ITC, ITE and BTE hearing aids: diary and interview reports from elderly users. AB - The advantages and disadvantages of in-the-canal (ITC), in-the-ear (ITE) and behind-the-ear (BTE) hearing aids for elderly aid users were examined. Two hundred and forty four clients were randomly assigned to one of the three aid types from seven hearing aid manufacturers. The clients' perceived help from their fitting, and the degree of difficulty they encountered over a range of listening situations and environments were rated using a daily diary and a structured interview. Findings indicated that for elderly clients there were no large practical advantages for one aid type over another. While ITC and ITE aids were rated more highly than BTE's in background noise, all three aid types were rated as relatively poor in background noise as well as in groups, in the wind, when using the telephone and in the localisation of sound. All three aid types were rated equally and well for performance in one-to-one conversation in quiet, and for listening to television and radio. Hours of use and reasons for non-use are presented, as are clients' reports on cosmetic issues, manipulative ease and overall satisfaction level with their aids. PMID- 2265301 TI - Hearing aid manipulation skills in an elderly population: a comparison of ITE, BTE, and ITC aids. AB - In-the-ear, in-the-canal and behind-the-ear hearing aids were compared for ease of management by elderly people. Two hundred and forty-four clients were randomly assigned to be fitted with one aid type, and rated for ability to perform the manipulative tasks necessary to enable effective use of the aid. It was found that in-the-ear aids were easiest to use, that females experienced greater difficulties in manipulation than males and that some tasks were easier to perform and more quickly learned than others. The findings are discussed in terms of design requirements and aid fitting practices. PMID- 2265302 TI - A finite element analysis of the natural frequencies of vibration of the human tympanic membrane. Part I. AB - The present work examines the natural frequencies of vibration of the decoupled human tympanic membrane using the finite element method. A model comprising 49 isoparametric semi-loof thin shell elements was built, based on shape measurements of Kirikae (1960) and our own measurements on several local cadaver ears. A range of material data input was used similar to that assessed earlier by Funnell and Laszlo (1978). The present results indicate the natural vibration mode shapes are simple at low frequencies, but become more complex at higher values as found earlier (Tonndorf and Khanna, 1972; Funnell and Laszlo, 1978), but at reduced frequencies. Data input of the real drum thickenesses and dimensions considerably increases the natural frequencies by about 50% above those for a uniformly thick membrane. It is suggested that realistic eardrum natural frequencies may result from the use of a membrane internal stress parameter in the data file in order to simulate the interplay between radial and circular fibres resulting in the observed drum curvature. PMID- 2265303 TI - Binaural hearing aids for high-frequency hearing loss. AB - A recent study has examined the differences between certain monaural and binaural frequency responses as used in hearing aids for persons with high-frequency (often noise induced) hearing loss, in terms of both speech discrimination score and subjective rating methods. Slight variations in speech discrimination score resulted from changing the frequency response of a monaurally fitted aid while subjective preferences favoured an aid with adaptive low-frequency gain regulation for more severe high-frequency losses. A much more pronounced improvement, was however found for a binaural fitting of the preferred aid, resulting in increased discrimination score and subjective ratings of sound quality, speech clarity and overall impression. A binaural fitting of a subjectively preferred monaural hearing aid produced speech discrimination scores which were at least as good as, if not better than, those obtained from the optimum monoaural fitting. These findings are thought to have important implications for the fitting of hearing aids. PMID- 2265304 TI - A comparison of different binaural hearing aid systems for sound localization in the horizontal and vertical planes. AB - Three groups of hearing-impaired listeners who had been fitted binaurally with behind-the-ear (BTE), in-the-ear (ITE), or in-the-ear-canal (ITC) hearing aids were tested on spatial localization function for sources in the frontal horizontal and vertical planes. No significant differences in unaided performance were observed between the groups, nor between that and aided performance in the BTE and ITE wearers. ITC wearers, by contrast, showed a deterioration in aided over unaided performance. From observations of performance when each group wore temporary fittings of the other two types of system, and from the performance of a non-impaired control group, it appears that the performance decrement for the ITC wearers was due to their own particular systems although specific reasons for this decrement could not be identified. In all conditions, aided and unaided, vertical plane localization was markedly disrupted in all the hearing impaired groups. It was also disrupted, to a lesser but still substantial extent, in aided conditions for the non-impaired listeners. PMID- 2265305 TI - Review of a high risk register for congenital or early-onset deafness. AB - This paper is an attempt to assess the success of a high risk register for congenital or early onset of severe to profound hearing impairment. With some years experience, and a large number of publications, it is possible to evaluate (at least in part) the extent to which such a register actually does permit us to identify these infants. To that end, an extensive review is reported here and some recommendations are made. PMID- 2265306 TI - Hearing aid fitting costs in the NHS. PMID- 2265307 TI - Reply to letter of Professor Haggard in answer to my original letter of March 1990. PMID- 2265309 TI - Morphological study of myocardial capillaries in endurance trained rats. AB - In this morphological study of the effects of training on myocardial capillaries, four week old Wistar rats were selected to accept four months of treadmill training. The rats were then sacrificed for morphological study of myocardial capillaries by means of perfused Chinese ink, AKP stain and ultrathin section methods. The results showed that the number of capillaries in trained rats was increased markedly by 14.8 per cent (P less than 0.05) in the outer layer and 13.7 per cent (P less than 0.05) in the inner layer. The ratio of capillaries to myocardial fibres was increased by 17.6 per cent and 13.7 per cent (P less than 0.05) respectively. The area and girth of capillaries in the trained rats were increased by 25 per cent and 26 per cent (P less than 0.01) respectively. Collateral branches in the trained rats were also increased and were more irregular in shape or appeared locally expanding and tortuous. Unopened capillaries were often observed in the control rats, while in the trained rats, no unopened capillaries were observed. In addition, the small vacuoles in the cytoplasm of endothelial cells were also increased. PMID- 2265308 TI - Effect of a herbal yeast food supplement and long-distance running on immunological parameters. AB - The effect of a food supplement on immunological parameters of 16 long-distance runners was tested in a randomized, double-blind and placebo-controlled trial. The supplement comprised plasmolysed herbal yeast, malt, honey, and orange juice. No statistically significant differences between the two groups regarding the following variables were detected at three sessions at rest and immediately after a 21 km run: total and differential white blood cell counts, numbers of B- and T cells and T-subpopulations, concanavalin-A-induced lymphocyte proliferation, serum levels of immunoglobulins, neopterin, IL-2 receptors, beta 2-microglobulin, complement factor b, c4 and c3c, and c1-inactivator. These findings suggest that the effects of the tested food supplement on these parameters are negligible with respect to improvements in the immunological status of long-distance runners. The changes observed immediately after the run had a transient character. In both groups, however, low lymphocyte counts, IgG subclass 2 levels and c1-inactivator levels were noted at rest, which indicate that the immune status of endurance athletes may be affected by training. PMID- 2265310 TI - Normal course of events amongst Swedish soccer players: an 8-year follow-up study. AB - In this study 180 male soccer players entered into a prospective study of injuries in 1980. They were examined again in 1988. The aim of the present study was to evaluate the course of events during their active period. The study was carried out using a questionnaire. The importance of major injuries was evaluated. Hospital records were scrutinized and 179 of 180 (99 per cent) were included in the evaluation. PMID- 2265311 TI - Rehabilitation after coronary artery by-pass grafting and improved quality of life. AB - Long waiting lists for coronary artery by-pass grafting often mean that patients have to endure a prolonged period of pre-operative disability, a known poor prognostic factor for their future quality of life and employment prospects. A survey of 60 patients who attended a post-operative rehabilitation course designed to restore their fitness and self-esteem, and hence their quality of life, has shown encouraging results. When questioned a mean 16 months later, 85 per cent are working and significant improvements have been seen in all four quality of life indicators assessed: job satisfaction, family life, social life and sex life. Significant improvements are also seen in their symptoms. Cardiac rehabilitation should be made more available following coronary artery by-pass grafting. PMID- 2265313 TI - An uncommon shoulder injury. PMID- 2265312 TI - Skiing injuries: a study from a Danish community. AB - A Danish investigation of skiing injuries is presented from the casualty wards of two hospitals. The material consisted of 119 skiing injuries. Fifty-three per cent of the patients were women. Eighty-three injuries occurred abroad, mainly in Austria and Norway. Injury rate was not related to sex. The highest injury rate was found in the age group 20 to 29 years old. The most frequent injuries were sprains (knee 43, finger 14), fractures (39) and contusions (19). Injuries requiring hospitalization were common. None of these resulted in permanent major disability. PMID- 2265314 TI - Intermittent axillary vein obstruction in a competitive canoeist. AB - The case is reported of a competitive canoeist with intermittent axillary vein obstruction secondary to shoulder girdle muscle hypertrophy. The anatomy of the axilla, pathology of the axillary vein, and reported cases of sports injuries involving the axillary vein are discussed. This would appear to be the first report of such an occurrence in a canoeist. PMID- 2265315 TI - World Transplant Games--Singapore, 1989. PMID- 2265316 TI - Blood or plasma lactate? PMID- 2265317 TI - Who owes the therapists? PMID- 2265318 TI - Society of Sports Therapists--a proposal. PMID- 2265319 TI - International Federation of Sports Medicine: physical exercise--an important factor for health. PMID- 2265320 TI - Establishing a pattern for sports medicine centres in Scotland. PMID- 2265321 TI - Sugars for success? PMID- 2265322 TI - Effect of split exercise sessions on excess post-exercise oxygen consumption. AB - In this study the excess post-exercise oxygen consumption (EPOC), and related metabolic measures, following a 50 minute run compared to two 25 minute runs all at 70 per cent of peak VO2 in six women were investigated. Open-circuit spirometry procedures were used and appropriate control conditions were maintained for all trials. Following exercise, VO2 returned to baseline within 30 minutes for all three exercise trials. Magnitude of EPOC was also similar after all runs. However, the combined magnitude (expressed in kcals) of the two 25 minute runs was significantly greater than the continuous 50 minute run (13.88 vs 6.39). Heart rate remained elevated above baseline, and respiratory exchange ratio was lower than baseline 30 minutes after exercise. It is concluded that split exercise sessions can significantly increase post-exercise caloric expenditure. However, the overall magnitude of the increase is small. PMID- 2265323 TI - Effect of a high carbohydrate diet on core temperature during prolonged exercise. AB - This study compared the effects of a high-carbohydrate and a mixed diet on core temperature responses to prolonged exercise in six male competitive cyclists (age = 22.2 +/- 1.9 years). This study, the first to investigate the effect of a high carbohydrate diet on exercise core temperature in humans, therefore suggests that three days of increased dietary carbohydrate intakes do not evoke any deleterious thermoregulatory responses during prolonged submaximal exercise. PMID- 2265324 TI - Intravenous urography revisited. PMID- 2265325 TI - Urological complications in 350 consecutive renal transplants. AB - Ten urological complications (2.9%) were found in 350 kidney transplants performed in this centre. These included obstructive uropathy (20%), urinary leaks (40%), distal uretic fistulas (necrosis) (30%) and renal calculi (10%). Two grafts were lost due to chronic rejection 9 and 30 months post-operatively. The remaining 8 patients have stable renal function (mean creatinine 1.5 mg%). It was concluded that meticulous surgical technique may reduce the number of urological complications and early diagnosis and prompt surgical treatment may help to save the grafts. PMID- 2265326 TI - Emphysematous pyelonephritis: surgical implications. AB - Emphysematous pyelonephritis in patients with diabetes mellitus is increasingly recognised as a disease requiring urgent and aggressive treatment. We present 3 cases of emphysematous pyelonephritis; 1 patient required percutaneous nephrostomy followed by nephroureterectomy but the other 2 were successfully managed with antibiotics and control of diabetes. Diagnosis was confirmed by sequential imaging techniques which demonstrated an inflammatory renal mass associated with gas and fluid. PMID- 2265328 TI - Do stone formers have lower urinary fibrinolytic activity than controls? AB - A comparison of urinary fibrinolytic activity between 31 stone formers and 50 controls failed to demonstrate any significant difference and so failed to confirm an earlier independent observation. This may be due to methodological and design differences between the 2 studies, but does suggest reservations about the significance of lowered urinary fibrinolytic activity as a risk factor for renal stone disease. Dietary information from those taking part in the study suggests that a reduction of meat intake by stone formers might be associated with increased urinary fibrinolytic activity. This might account for the discrepancy between the 2 studies, in which case this observation could be of significance. PMID- 2265327 TI - Excretion of urinary protein induced by extracorporeal piezoelectric lithotripsy. AB - An investigation was carried out into renal injury caused by extracorporeal piezoelectric lithotripsy (EPL) using an EDAP lithotriptor. Four urinary proteins, with a molecular weight range of 160000-14500, immunoglobulin G (IgG), N-acetyl-beta-glucosaminidase (NAG), albumin and lysozyme, were monitored in 27 patients 1 day before and 1, 7, 30, 90 and 180 days after unilateral EPL treatment. All patients had non-obstructive renal stones, previously untreated. Apart from 5 patients with stablised hypertension and 6 with persistent urinary infections due to the infected stones, all patients appeared healthy, as confirmed by clinical, haematological and biochemical investigations. Only albumin levels increased significantly 1 day after treatment; statistically nonsignificant increases and decreases were recorded in the levels of NAG and lysozome respectively. IgG was beyond the limit of detection (less than 0.5 mg%) in all patients. The albumin level returned to normal 7 days after treatment. The EPL-induced increase in albumin was recorded in 88% of patients, compared with increased levels of NAG in 46% and lysozyme in 64%, mainly in those with infected stones. These findings indicated a transient glomerular injury after EPL treatment. PMID- 2265329 TI - Renal angiomyolipoma: report of 24 cases. AB - A series of 24 patients with renal angiomyolipoma was reviewed. Their ages ranged from 10 to 70 years (average 41). Four cases were associated with tuberous sclerosis, 1 with spinal neurilemmoma, 1 with transitional cell carcinoma and another with renal tuberculosis. The presenting symptoms in decreasing frequencies were flank pain, mass, haematuria, fever, syncope and respiratory distress. Although it has often been said that angiomyolipomas associated with tuberous sclerosis are small and asymptomatic, all 4 such patients in this study had large symptomatic tumours. Before the advent of CT scan and ultrasonography, the pre-operative diagnostic rate for cases unassociated with tuberous sclerosis was 10% (1/10). With the combined use of these 2 modalities, the diagnostic rate increased to 60% (6/10). Most patients in this series were treated with nephrectomy. However, equally good outcomes occurred in 2 patients who received partial nephrectomies. Pre-operative diagnosis now makes it possible to consider more conservative management. PMID- 2265330 TI - The effect of verapamil on the anti-tumour action of mitozantrone and doxorubicin against renal carcinoma cells in vitro. AB - Ten renal carcinomas were established in culture and their sensitivity to mitozantrone +/- verapamil, as measured by (75Se) selenomethionine incorporation, was studied. The 5 tumours with spread beyond the kidney were those in which sensitivity to mitozantrone was enhanced by verapamil. With 4 of the 10 tumours and 1 further carcinoma, similar experiments were performed using doxorubicin. This drug was more active, its anti-tumour action being related to concentration. Verapamil was more effective in potentiation of doxorubicin and this action increased in proportion to the concentration of verapamil added. PMID- 2265331 TI - Treatment of renal colic by prostaglandin synthetase inhibitors and avafortan (analgesic antispasmodic). AB - In a study of the pain-relieving effect of 3 drugs commonly used to treat acute renal colic in this hospital, intravenous indomethacin and intramuscular diclofenac (prostaglandin synthetase inhibitors) were compared with intravenous Avafortan (analgesic antispasmodic). As first-line analgesics, prostaglandin synthetase inhibitors, if given intravenously, offer an effective alternative to Avafortan. Of 145 patients studied, 32 required a second injection for complete relief of pain. Administering a second dose of prostaglandin synthetase inhibitors resulted in equally significant pain relief rate even though the route was intramuscular. PMID- 2265332 TI - Evaluation of a bladder advancement extension graft technique. AB - A bladder advancement extension technique was developed to provide a reliable method for creating an extra length of bladder in continuity, so that Boari flap and psoas hitch procedures, with or without the extension grafts, would reach sufficiently high routinely to permit these procedures to become the preferred practical options for accommodating significant proximal ureteric deficiencies or for replacing the whole of the ureter. In addition, an omentally supported bladder graft was established separately for use in a "retrieval" procedure should extension graft stenosis develop subsequently. Of 10 dogs studied for 6 months, 2 required "retrieval" pedicled island patch grafts for stenoses at extension graft/upper ureteric junctions. Healthy urothelium with muscle in the walls was seen in grafts resting on their supporting omental beds. At the time of sacrificing, none of the operated upper tracts was obstructed. PMID- 2265333 TI - Caffeine: does it affect your bladder? AB - Patients with symptoms of frequency and urgency often complain that their symptoms are exacerbated by tea or coffee. A series of 20 women with confirmed detrusor instability and 10 asymptomatic women were given 200 mg of caffeine citrate and urodynamic studies were performed. In the group with detrusor instability there was a statistically significant increase in detrusor pressure on bladder filling following administration of caffeine, but no difference in volume at first contraction, height of contraction or bladder capacity. Normal women had no abnormality on cystometry. PMID- 2265334 TI - Experience with a simplified technique for the treatment of female stress urinary incontinence. AB - Over a 9-year period a simple procedure for the correction of stress urinary incontinence was performed in 86 consecutive patients, 31 of whom had failed a previous anti-incontinence procedure. Success was achieved in 81 cases (94%). Of the 5 failures, 2 were successfully treated with a repeat procedure. Operative time ranged from 14 to 49 min (median 27). The average hospital stay was 2 days. Because of its simplicity and reliability, this technique is recommended for the surgical correction of female stress urinary incontinence. PMID- 2265335 TI - Urinary continence in spinal injury patients following complete sacral posterior rhizotomy. AB - Complete sacral posterior rhizotomy was carried out in 15 spinal injury patients in conjunction with implantation of sacral anterior root stimulators. All patients were incontinent pre-operatively and had video-pressure cystometry before and at regular intervals after surgery. Detrusor hyper-reflexia was totally abolished in all but 1 patient following rhizotomy and 87% no longer require any form of incontinence appliance. Deafferentation produced adverse changes in vesicourethral function and even when rhizotomy was complete, continence could not be guaranteed. The pre-operative state of the bladder neck and distal sphincter mechanism had an important bearing on future continence and those patients with a closed bladder neck and no previous sphincterotomy had the greatest chance of becoming continent after deafferentation. The majority of patients in this series are now fully continent, representing a transformation in their quality of life; it is recommended, however, that to optimise the success of rhizotomy precise pre-operative evaluation and selection of patients are essential. PMID- 2265336 TI - Ten cases of transitional cell carcinoma of bladder causing ureteric obstruction. AB - A review was carried out on 10 patients with superficial transitional cell carcinoma of the bladder (Ta lesions) that were causing ureteric obstruction. Evidence of upper tract obstruction did not necessarily indicate deep invasion. PMID- 2265337 TI - Acute epididymitis: why patient and consort must be investigated. AB - In this prospective study of 49 patients under 35 years of age with clinically diagnosed epididymitis, detailed microbiological investigation identified an infective cause in 67%. Chlamydia trachomatis was the commonest agent, present in 25 patients, but in 12 of these detection was based solely on raised antibody titres; 20 of the 28 female consorts screened were partners of men with chlamydial epididymitis and 80% of them were also positive for this infection. Isolating the micro-organism from 14 of 16 consorts indicated active infection despite the negative swabs from the men. If this important infection is to be adequately treated we recommend that all patients in this age group with epididymitis and their partners should be referred to a specialist unit with access to full chlamydia laboratory facilities. PMID- 2265338 TI - Epidermoid cyst (monodermal teratoma) of the testis. AB - We report 14 patients with epidermoid cyst of the testis (monodermal teratoma). In 7 patients (5 treated within the last 5 years) the mass was excised and adjacent testicular tissue was biopsied. Seven patients underwent radical inguinal orchiectomy. Carcinoma in situ was not detected in any testicular tissue examined. There was no evidence of tumour recurrence in any patient after a mean follow-up of 10 years. Ultrasonographic appearance was not specific for a diagnosis of epidermoid cyst and exploratory surgery was required in all cases. Excision of the tumour and biopsy of adjacent testicular tissue to determine the presence or absence of carcinoma in situ is adequate treatment for this rare testicular neoplasm. PMID- 2265339 TI - Comparison of urethral reaction to full silicone, hydrogen-coated and siliconised latex catheters. AB - Indwelling urinary catheter may induce an inflammatory reaction or even stricture of the urethra. Catheter encrustation and urinary infection are other disadvantages associated with long-term catheterisation. In the present study, 77 male patients were catheterised randomly as part of their normal treatment with 1 of 3 different types of catheter: 22 siliconised latex, 28 hydrogel-coated latex and 27 full silicone catheters. The mean duration of catheterisation was 2.2 days. The urethral inflammatory reaction was assessed from cytological urethral swab specimens. Catheter encrustation was studied using scanning electron microscopic (SEM) analysis. The full silicone catheters induced the mildest degree of inflammation in the urethra, the percentage mean of inflammatory cells in smears being 20%. In both latex catheter groups the value was 36%. Neither the age of the patients nor the duration of catheterisation had any effect on the inflammatory reaction, which was more marked in patients with haemodynamic abnormalities. The hydrogel coating effectively prevented encrustation, while siliconised latex catheters were the least resistant to encrustation. The inflammatory reaction was variable in all patients. The use of urethral catheters should be restricted and suprapubic tubes should be used instead, particularly in patients with shock-like circulatory changes. By developing the biocompatibility and physical properties of urinary catheters, more compatible devices may be manufactured. PMID- 2265340 TI - Haemospermia as a presenting symptom of lymphoma. PMID- 2265341 TI - Carcinoma of the bronchus and metastases from an occult testicular tumour. PMID- 2265342 TI - Necrotising testicular vasculitis associated with dermatomyositis. PMID- 2265344 TI - Inverted papilloma of the penile urethra. PMID- 2265343 TI - Beware of antacids! PMID- 2265345 TI - Phimosis associated with mycosis fungoides. PMID- 2265346 TI - Osteogenic differentiation in a sarcomatoid renal carcinoma. PMID- 2265347 TI - Retained catheter tip causing recurrent urinary tract infection in a 91-year-old man. PMID- 2265348 TI - Intramural vesical abscess. PMID- 2265349 TI - Reduction of paraphimosis. PMID- 2265350 TI - Easy localisation of stones on ultrasound monitored lithotriptors. PMID- 2265351 TI - Safer nephroureterectomy in the treatment of transitional cell carcinoma of the upper urinary tract. PMID- 2265352 TI - Re: Endoscopic transvesical extramural ureterolithotomy. PMID- 2265353 TI - Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines. AB - We have localized neurotensin (NT) with immunocytochemical methods in the normal human cerebral cortex. Extensive areas of the frontal cortex, the hippocampal formation, and selected areas of the parietal, temporal and occipital lobes, were examined using post-mortem brain tissue. The peptidergic innervation was characteristically restricted to the limbic belt and to the dorsally contiguous regions. NT-labeled perikarya were found throughout the subiculum, including its dorsal supra-callosal continuation. NT terminal plexuses were particularly abundant in layers I-VI of the anterior cingulate cortex, in layer I of area 32 and of medical areas 9, 8, 6 and in layers II-III of area 29, of the presubiculum and entorhinal cortex. Elsewhere, NT fibers were scarce being more frequent in layer I. This regional and laminar pattern differed significantly from that of tyrosine hydroxylase (TH), which was used to label catecholaminergic axons, and preferentially the dopaminergic ones. Even in zones where TH and NT innervations were abundant, such as the anterior cingulate cortex or area 32, double-labeling procedures disclosed no colocalized fibers. The lack of NT-TH colocalization in human, contrasts with previous findings in the rodent cortex, where a contingent of the DA cortical afferents contains NT. The DA mesocortical neuronal population, labeled by TH antisera, thus seems to change its chemical phenotype, by losing the expression of an associated peptidergic neurotransmitter; this could be related to the predominant extension in the ascent of the phylogenetic scale of the non-colocalized, type of cortical DA innervation which is also found in rodents. The possible origins of the cortical, non-dopaminergic NT innervation in human are discussed: thalamo-cortical, subiculo-cortical or intrinsic. Such cortical NT innervation could be very important in limbic circuitry as a regulatory peptide in affective processes and could be involved in the physiology of pain and memory. PMID- 2265354 TI - Excitation and inhibition of rat sympathetic preganglionic neurones by catecholamines. AB - The actions of microiontophoretically applied catecholamines on antidromically identified sympathetic preganglionic neurones (SPN) in the upper thoracic spinal cord of the anaesthetized rat were investigated. Noradrenaline (NA) excited the majority of neurones (50/71), however, a significant number were inhibited by the catecholamine (17/71). Adrenaline excited 4/9 SPN and inhibited 2/9. Dopamine had excitatory actions on SPN (3/3). Dual actions of NA on the same SPN were demonstrated, with the actions of the catecholamine being modulated by excitatory amino acids. NA was also shown to induce burst firing in 21% of SPN. PMID- 2265355 TI - Immunological evidence that the neural adhesion molecule L1 is expressed in fish brain and optic nerve: possible association with optic nerve regeneration. AB - In the mammalian peripheral nervous system (PNS), expression of the neural adhesion molecule L1 on Schwann cells and neurons has been correlated with axonal growth during development and regeneration. The present study was undertaken to examine whether a similar correlation exists between a lesion-induced increase of L1 expression and regenerative capacity in the central nervous system (CNS). The fish optic nerve was used as a model for a successfully regenerating region of the CNS. Immunochemical and immunohistological experiments carried out with immunoaffinity purified polyclonal antibodies, generated against L1 from mouse brain, showed that carp optic nerve and brain, but not liver, contained L1 immunoreactivity. Western blot analysis of brain tissue yielded one distinct band at 200 kDa, while a double band at 200 kDa and two low-molecular weight bands at 120 and 100 kDa, possibly degradation products, were seen in the optic nerve. Immunohistological examination of normal optic nerves revealed L1 immunoreactivity, predominantly associated with connective tissue boundaries of nerve fascicles and with blood vessels, as well as inside axonal fascicles. L1 immunoreactivity was increased by 25%, 8 days after crushing of the optic nerve, as determined by radioimmunoassay on a nerve segment distal to the site of injury and compared with untreated control nerves. Increased levels of L1 were also seen by immunohistology and found to be predominantly associated, as in the normal nerve, with connective tissue boundaries and blood vessels. These observations suggest that a lesion-induced increase in L1 expression in the fish optic nerve is associated with axonal regrowth in the CNS. PMID- 2265357 TI - Postischemic alterations of spontaneous activities in rat hippocampal CA1 neurons. AB - Changes of spontaneous impulse discharges in rat hippocampal neurons during and after transient forebrain ischemia were investigated electrophysiologically. Spontaneous impulse frequencies of CA1 neurons before ischemia were varied from 0.4 to 20.0 impulses/s and its average was 5.8 +/- 1.2 (means +/- S.E., n = 36). These spontaneous discharges were completely suppressed during forebrain ischemia except for the transient hyperactivity observed just after the beginning of ischemia. Recovery of spontaneous discharges of CA1 neurons from suppression induced by 5 min ischemia started at 5 min, and neuronal activities were restored to pre-ischemic levels approximately 30 min after reperfusion. On the other hand, spontaneous impulse frequencies at all time points recorded after 20 min ischemia were less than 40% of the pre-ischemic levels. These continuous suppression of spontaneous activity after 20 min ischemia may suggest that neuronal function is impaired during and/or in the early stages of reperfusion, and functional disorders precede morphological degeneration. PMID- 2265356 TI - Interactions of methylmercury with rat primary astrocyte cultures: inhibition of rubidium and glutamate uptake and induction of swelling. AB - The ability of astrocytes to sequester MeHg may indicate an astrocyte-mediated role in MeHg's neurotoxicity. Hence, studies were undertaken to assess the effects of MeHg on metabolic functions in cultured astrocytes. MeHg (10(-5) M) significantly inhibited the initial rate (5 min) of uptake of 86RbCl, used as a tracer for K+. 86RbCl uptake was also sensitive to the omission of medium Na+. MeHg (10(-5) M) also markedly inhibited the initial rate of uptake (1 min) of the Na(+)-dependent uptake of [3H]L-glutamate. A second neurotoxin, MnCl2 (0-5 x 10( 4) M), did not alter [3H]glutamate or 86RbCl uptake. MeHg, but not MnCl2, also stimulated the release of intracellular 86Rb+ in a dose-dependent fashion. This effect could be prevented by the administration of MeHg as the glutathione conjugate. These observations support the hypothesis that the astrocyte plasma membrane is an important target for MeHg's toxic effect and specifically that small concentrations of this organometal inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, resulting in cellular swelling. We therefore studied volume changes in astrocytes using uptake of [14C]3-O-methyl-D-glucose, in attached cells in response to exposure to MeHg. Exposure to MeHg (0-5 x 10(-4) M) caused a marked increase in the cell volume that was proportional to concentrations of MeHg. PMID- 2265358 TI - Cerebral hemodynamics during cortical spreading depression in rabbits. AB - Effects of a single cortical spreading depression (CSD), elicited by KCl microinjection, on diameter of pial arterioles and venules in the parieto occipital cortex were examined in urethane-anesthetized adult rabbits using a closed cranial window. The velocity of CSD propagation was 2.7 +/- 0.1 mm/min (mean +/- S.E.M.). All arterioles (n = 39) except for those in the retrosplenial region (n = 6) increased their diameter significantly during CSD. The arteriolar dilation lasted for 1.5 +/- 0.1 min. Location of dilating arteriole and propagating CSD showed that they were always closely associated temporally. As a percentage change, diameters of smaller arterioles significantly increased (from 60 +/- 1 to 103 +/- 2 microns, 71%, n = 12) more than those of larger ones (from 82 +/- 2 to 129 +/- 3 microns, 57%, n = 27). While venules with initial diameter of 85 +/- 4 microns (n = 5) did not dilate, those with initial diameter of 49 +/- 3 microns increased to 57 +/- 3 microns (16%, n = 8) for 1.4 +/- 0.2 min during CSD. The majority of the dilated venules started to increase their diameter after nearby arterioles had dilated maximally. Pial arterioles, which dilated during ipsilateral CSD, decreased their diameter significantly from 78 +/- 2 to 72 +/- 3 microns (8%, n = 11) during contralateral CSD for 13.8 +/- 3.6 min with similar onset latencies as those observed for the dilation. Indomethacin pretreatment significantly enhanced arteriolar dilation during CSD (from 73 +/- 4 to 138 +/- 6 microns, 89%, n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265359 TI - Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen insensitive mechanism. AB - Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the gamma-aminobutyric acid (GABA) agonists muscimol or baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAA and GABAB receptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAA receptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen. GABAergic antagonists when given alone did not induce phase shifts. Collectively, these studies indicate that when activated by exogenous GABAergic agents, a GABAergic system associated with both GABAA and GABAB receptors exists as a neural regulatory mechanism that can reset the mammalian circadian clock. However, GABAergic synaptic pathways may not be normally involved in the circadian timing system. PMID- 2265360 TI - Functional significance of the apamin-sensitive conductance in rat locus coeruleus neurons. AB - The effects of apamin on rat locus coeruleus (LC) neurons were studied in a brain slice preparation with intracellular recording. Bath application of apamin (2-500 nM) reduced the amplitude of an intermediate component of the afterhyperpolarization (AHP) following single spontaneous action potentials, but did not change the size or time-course of fast and slow components of the AHP, spike amplitude or duration. Apamin blocked the early component of the post stimulus hyperpolarization (PSH) which follows a train of action potentials. The size of the late component of PSH was sometimes augmented by apamin. Apamin increased the number of spikes evoked by a depolarizing current pulse and increased the slope of the spike frequency-current intensity relation. Accommodation of firing during long depolarizing pulses showed a biexponential time-course indicating 2 distinct components. Apamin specifically reduced the contribution of the fast component of accommodation and increased its time constant. These data indicate that the apamin-sensitive conductance is functionally important in accommodation at faster firing rates such as those seen during evoked spike trains in the present experiments, and which may occur in vivo during behavioral arousal and in anxiety or drug withdrawal syndromes. PMID- 2265362 TI - The effects of exogenous neuropeptide Y on feeding and sexual behavior in the red sided garter snake (Thamnophis sirtalis parietalis). AB - Actively courting adult male red-sided garter snakes were injected with one of two dosages of neuropeptide Y (NPY) or saline into the third cerebral ventricle. Courtship and feeding responses were assessed prior to surgery, 4-5 h and 24 h post-surgery. Feeding behavior was tested by the presentation of a favored food, an earthworm. NPY significantly reduced courtship behavior scores at both low (0.16 nmol) and high (0.77 nmol) doses 4-5 h after surgery. Snakes also took much longer to reach the criterion courtship score at the high dose. Feeding occurred only in snakes treated with NPY. At the low dose 29% ate at 4-5 h and 24 h after surgery; 43% of the snakes treated with the high dose ate 4-5 h post-surgery. When tested the day following injection, animals were courting at levels comparable to presurgery levels and refused food. PMID- 2265361 TI - [3H]prazosin binding in the intermediolateral cell column and the effects of iontophoresed methoxamine on sympathetic preganglionic neuronal activity in the anaesthetized cat and rat. AB - The autoradiographic localization of [3H]prazosin (alpha 1-adrenoceptor ligand) binding sites was determined in cat spinal cord sections. High levels of [3H]prazosin binding were found in the intermediolateral cell column (IML) at thoracic and lumbar levels. The iontophoresis of the alpha 1-adrenoceptor agonist methoxamine onto sympathetic preganglionic neurones (SPNs) in anaesthetized cats and rats caused excitation of 8 cat SPNs and 13 rat SPNs. These results suggest an excitatory role for some of the catecholaminergic innervation of the IML. PMID- 2265363 TI - Lesion of the anteroventral third ventricle region abolishes the beneficial effects of hypertonic saline on hemorrhagic shock in rats. AB - The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arterial pressure (MAP) during hemorrhage was studied in sham operated rats and in rats with electrolytic lesion in the anteroventral third ventricle (AV3V) region. After intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.), MAP increased from about 60 to 90 mmHg in sham rats and became stable at this level during all the time of observation (30 min). In AV3V-lesioned rats, after the same infusion, the MAP increased to 80 mmHg, but returned to the pre-infusion levels within 30 min. These results show that the integrity of the AV3V region is important for the beneficial effect of HS during hemorrhagic shock in rats. The AV3V lesion disrupts neural pathways involved in the maintenance of fluid balance and these changes probably abolish the effect of hypertonic saline. PMID- 2265364 TI - Evidence for central patterning of sympathetic discharge in kittens. AB - Cervical sympathetic nerve discharges in kittens were examined using power spectral techniques to describe the frequency components of nerve activities and to obtain evidence of modulation by central rhythm generators. Peaks in sympathetic spectra appeared in the 4-11 Hz band; however, coherences between sympathetic nerves occurred at 4-5 Hz, while that between sympathetic and phrenic nerves occurred at 8-9 Hz. These findings indicate modulation by sympathetic and inspiratory rhythm generators. PMID- 2265365 TI - [Diagnostic importance of laboratory indicators in persons with alcoholism]. AB - We investigated the diagnostic significance (efficacy) of 15 laboratory parameters in a group of 147 males (69 practically healthy volunteers and 78 alcoholics). We found that determination of IgA is of the greatest diagnostic value. This is followed by activity of gamma-glutamyltranspeptidase and aspartate transaminase, whilst IgG is in the fourth place and coeruloplasmin in the sixth place. Results of our study indicate that none of followed parameters can be suggested as the only marker of chronic alcohol intoxication. A way to enhancement of diagnostic significance of laboratory parameters may be application of multifactorial analysis with the use of a group of clinical and laboratory parameters. PMID- 2265366 TI - [Surface integral maps, their characteristics and methods of quantitative analysis]. AB - Integral maps (IM) enable considerable reduction of measured data with preservation of all characteristics of electric field of the heart with exception of the time sequence of activation. Review article offers a definition of the term IM and explains the mode of their construction, depiction and analysis as well as the principles of derivation and variation maps. A review of qualitative and quantitative parameters used in analysis of IM in humans is given. There are also mentioned modes of comparison of IM from simple, directly readable parameters to complicated mathematical and statistical methods of processing. PMID- 2265367 TI - [Comparison of the reactivity of pulmonary tissue and pulmonary vessels in ontogenesis]. AB - Reactivity of the lung tissue and of a. pulmonalis has been followed by means of isometric contraction of isolated strips. Histamine, acetylcholine and prostaglandin F2 alfa (PGF2 alfa) contracted the lung strips, the amplitude of histamine and acetylcholine induced contraction being significantly higher in grown guinea pigs than in foetuses. Strips of a. pulmonalis reacted with contraction in response to histamine and PGF2 alfa, they were non-reactive against acetylcholine. Magnitude of response of the strips of a. pulmonalis obtained from grown animals was significantly greater only after administration of PGF2 alfa in concentration of 10(-4) mol.l-1. Values of EC50 were significantly changed only by influence of acetylcholine on the lung strips. Isolated preparations of lung and vessel strips allow to characterize pharmacodynamic properties of the lung tissue. They represent a contribution to the evaluation of lung reactivity to xenobiotics. PMID- 2265368 TI - [The effect of acute administration of ketanserin on the peripheral metabolism of serotonin and hemodynamic indicators in hypertensive patients]. AB - The effect of IV administration of ketanserin (Janssen Pharmaceutica, Beerse, Belgium) on peripheral serotonin (5HT) metabolism and on hemodynamic parameters was compared with the placebo effect. Ten hypertensive patients were infused placebo (400 ml of 5% glucose) or received 20 mg ketanserin IV followed by infusion of 20 mg ketanserin in 400 ml of 5% glucose. Increase in platelet 5HT consent without changes in plasma 5HT plasma levels, increase in urinary 5HT excretion and decrease in 5-hydroxyindole-acetic acid (5HIAA) excretion were observed under ketanserin administration compared to the placebo period. Blood pressure dropped effectively under ketanserin. Total peripheral resistance (TPR) decreased markedly in 2 patients with high initial TPR values. No changes in circulating volume, hematocrit and diuresis were observed. No correlation was found between the parameters of peripheral 5HT metabolism and water metabolism. The decrease in urinary 5HIAA excretion reflected presumably the decreased platelet turnover. The increase in urinary 5HT excretion may have resulted from increased 5HT availability for the proximal tubular cell transport system of organic cations or it may have been the consequence of altered renal 5HT metabolism caused by ketanserin. The concurrent increase in platelet 5HT content and decrease in platelet aggregation indicates a stabilizing effect of ketanserin on hyperactive platelets in hypertensive patients. The effect of ketanserin on platelet turnover is presumably involved in the mechanism of its antihypertensive and antiaggregatory action. PMID- 2265369 TI - Preservation surgery of the spleen. AB - Authors point out possibilities of preservation of the spleen or its parts in injuries and some diseases, especially non-parasitic cysts. Review is completed by a case report of successful management of a splenic pseudocyst by partial resection. PMID- 2265370 TI - Role of CA125 and abdominal pelvic computerized axial tomogram in the monitoring of chemotherapy treatment of ovarian cancer. AB - Twenty four patients with epithelial ovarian cancer, who were treated by chemotherapy after debulking surgery, were monitored by serial monthly CA125 estimation and half-yearly computerized axial tomogram (CAT) of abdomen and pelvis. The efficiency of these monitoring methods and that of clinical examination were compared. The use of CA125 alone was superior to the use of clinical assessment alone in the detection of tumor progression (p less than 0.01). The addition of the expensive routine half-yearly CAT examination did not improve the tumor detection rate (p less than 0.05). Hence, CAT examination should not be used routinely to detect recurrence of tumor in patients without a raised CA125 level. However, in patients with increased CA125 level, CAT examination had a place in locating and in determining the extent of the tumor which in selected patients may enable us to make changes in therapy without laparotomy and in other patients may help us to make a better assessment on whether further debulking is possible. PMID- 2265371 TI - Randomized phase II study of a combination of cisplatin (DDP), 5-fluorouracil (5 FU), and allopurinol (HPP) versus 5-FU in advanced colorectal carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group study. AB - In order to improve the therapeutic index of fluorouracil (5-FU), it has been combined with cisplatin (DDP) as synergistic agent and with allopurinol (HPP) as toxicity modulator. Patients with measurable colorectal carcinoma, previously untreated by chemotherapy, were randomized to receive either 5-FU alone 500 mg/m2 push iv days 1-5 or HPP 3 x 300 mg po, days 1-5, 5-FU 800 mg/m2 push iv, days 3-5 and DDP 50 mg/m2 d6. Treatment was repeated every 4 weeks. Of 104 patients randomized, 82 were evaluable for response and survival. Six partial responses were seen in each treatment group (15%) and the median survival time was 7 months. Hematologic toxicities were comparable in both treatment groups, with a mean nadir white blood cell count of 3500/ vs. 3800/mm3 and a mean nadir platelet count of 148,000/ vs, 203,000/mm3 for HPP-5-FU-DDP and 5-FU, respectively. This study suggests that the addition of both HPP and DDP does not improve the activity of 5-FU. PMID- 2265372 TI - A phase II trial of sequential MTx and 5-FU alternated with 4-epidoxorubicin and cisplatin in advanced gastric cancer. AB - Twenty-one patients with advanced gastric adenocarcinoma were treated with a combination chemotherapy schedule of sequential methotrexate and 5-fluorouracil alternated with 4-epidoxorubicin and cisplatin. This scheme was active, with 7 partial responses leading to a response rate of 33% (+/- 20%). In two cases the tumor became operable. No severe toxicity developed and the treatment was usually well tolerated. PMID- 2265373 TI - Lonidamine and human lymphoblastoid alpha interferon in metastatic cancer: a phase I study. AB - The purpose of this study was to test the qualitative and quantitative toxicity of lonidamine (L) and alpha-interferon (IFN alpha) when used together, and to observe any apparent synergistic activity in conventionally untreatable measurable metastatic cancer. Eleven patients (8 males and 3 females) were enrolled. There was one response seen as measured by conventional criteria. There is no evidence that these agents are additive at this dose schedule, nor is their apparent synergistic activity. PMID- 2265374 TI - Mechanisms of organ specificity in chemical carcinogenesis. PMID- 2265375 TI - The retinoblastoma gene: its role in human malignancies. PMID- 2265376 TI - Indirect cost rates. What they are and how they reached their current levels. PMID- 2265377 TI - Noninvasive technology assessment: how should treatment of ovarian carcinoma be assessed? PMID- 2265378 TI - Anaplastic transformation of multiple myeloma. PMID- 2265380 TI - Critical care of the transplant patient. PMID- 2265379 TI - Is altruism enough? Required request and the donation of cadaver organs and tissues in the United States. AB - The lack of an adequate supply of cadaver organs and tissues for transplantation to those in need poses a major challenge to the transplant community and to those responsible for public policy. Historically, Americans have relied upon a combination of altruism and voluntarism to generate an adequate supply of cadaver organs and tissues. The ongoing shortage of organs and tissues has led, in recent years, for calls to abandon these values in favor of either a market system or a system of presumed consent. A survey of the impact of the federal and state laws that require that requests be made to next of kin for organ and tissue donation when a death occurs in a hospital setting shows that inadequate efforts have been made to implement these laws. Before abandoning altruism and voluntarism, health care professionals must insist that zealous efforts in education, enforcement, and coordination be made to implement these new laws and regulations. PMID- 2265381 TI - Solid organ transplantation. Where has it been, where is it going? AB - Current developments in the field of clinical transplantation have led to the proliferation and expansion of the indications for various surgical procedures. Elderly patients, individuals who are at high risk of developing complications during or after the transplant procedure, and extremely ill individuals whose only chance of survival is an immediate transplant increasingly are being considered as potential recipients. The often complex nature of the underlying disease of the transplant patient, the magnitude of the transplant procedure itself, and the potential severity of ensuing complications that are often unique to this group of patients frequently lead to examination and treatment of the patient in the intensive care unit. The preoperative evaluation, intraoperative monitoring, and postoperative care of such patients have become a critical mainstay to their recovery, and are the focus of other articles in this issue. PMID- 2265382 TI - The organ donor. AB - Vascularized organ transplantation is now a widely applied therapy for patients with end-stage diseases of the heart, lungs, liver, kidneys, and pancreas. A critical shortage of donor organs exists in the United States and, as a consequence, prospective transplant recipients die while waiting for a life saving transplant. The apparent shortage of cadaver organs is, in large part, caused by the reluctance and failure of the physician and the public to promote cadaver organ donation. Educational awareness programs for both professional personnel and the public at large are needed to increase the number of potential donors and multiorgan procurements carried out. All victims of trauma with severe closed head injury or cerebrovascular catastrophe secondary to anoxia should be considered as potential organ donors and referred to the local organ procurement agency for evaluation. PMID- 2265383 TI - Principles of immunosuppression. AB - One-year graft survival rates of 80% to 90% can now be achieved routinely for primary cadaveric transplants with a variety of CSA-containing regimens. Further improvement of these excellent results may be difficult because large numbers of patients must be evaluated to provide meaningful conclusions. On the other hand, long-term follow-up of CSA-treated patients has revealed a trend of undaunted allograft attrition with time. Future efforts therefore should be directed at improving long-term allograft results at 5 to 10 years. Further improvement of transplant outcome may be sought through better use of the currently available immunosuppressants or from newer agents. The long-term impact of CSA administration requires further evaluation. Although potent combination protocols provide effective protection against rejection, the potential development of neoplasms must be studied in long-term follow-up. On the other hand, unwarranted fear of progressive nephrotoxicity may result in underdosing of CSA and a high incidence of late rejections. The advent of mAbs has spawned an exciting era of specific immunosuppression. These newer agents may eventually help curtail the complications associated with the current regimens. PMID- 2265384 TI - General principles of perioperative transplant care. AB - Along with the development of more specific and potent immunosuppressive agents, improvements in perioperative care of the allograft recipient have made transplantation of nonrenal organs a reality and contributed greatly to overall improvements in graft and patient survival. Thorough pretransplant evaluation, intensive care therapy and monitoring (when indicated), and meticulous postoperative care are essential to a successful outcome and to minimize the occurrence of complications. PMID- 2265385 TI - Renal transplantation. AB - Results of renal transplantation have markedly improved in the last decade. Patients previously defined as high risk (those aged greater than 50 years, infants, diabetics, and those with extra renal disease processes) can now be transplanted with excellent outcomes. Living related donors are preferred because of the improved success rates. PMID- 2265386 TI - Liver transplantation. AB - Organ transplantation offers increased survival and improved quality of life to many patients with end-stage liver disease. Major advances in this field have included better organ acquisition and preservation as well as improved intraoperative techniques and management. An additional major factor in improved survival of transplant recipients is the elevated level of care available in intensive care units. Diligent postoperative care has led to early recognition and appropriate treatment of complications that previously were fatal. The intensive care unit team, in tandem with the transplant surgical service, significantly contributes to the successful outcome of the liver transplant recipient. PMID- 2265387 TI - Cardiac transplantation. AB - With the advent of cyclosporine and triple-drug therapy, cardiac transplantation has developed from a curiosity into an effective therapy. Optimal results require proper recipient selection, careful donor identification and preparation, and skillful surgical and postoperative care. Recent trends to expand the donor and recipient pools will result in an amplification of the problems encountered to date. Causes of significant perioperative morbidity and mortality continue to be graft failure, infection, and rejection. Careful attention to elevated recipient pulmonary vascular resistance and donor heart preservation are essential to prevent graft failure. Diagnosis and treatment of infection and rejection depend on anticipation and vigilance by the cardiac transplant team. Knowledge of and familiarity with immunosuppressive regimens and the inherent side effects, both unique to each drug and common to the group, should enable minimization of the drugs' toxicities. Long-term sequelae of cardiac transplantation are now being defined and our ability to affect them is a continuing challenge. Cardiac transplantation has become a safe and effective treatment for end-stage cardiovascular disease. Success is now measured, not by patient survival, but by the quality of life achieved by those who receive this treatment modality. PMID- 2265388 TI - Pancreas transplantation. AB - Widespread application of pancreas transplantation in diabetic patients without secondary complications or without a demonstrated propensity to develop complications will not be possible until antirejection strategies with fewer side effects have been developed. For now, pancreas transplants are restricted to patients whose complications of diabetes are more serious than those associated with chronic immunosuppression and the drugs necessary to prevent rejection. In these individuals, however, pancreas transplantation should be considered an established therapeutic procedure. PMID- 2265389 TI - Problems related to immunosuppression. Infection and malignancy occurring after solid organ transplantation. AB - Renal transplantation is associated with many long-term complications caused by a combination of the patient's comorbid medical illnesses and the effects of the various maintenance immunosuppressive agents currently in use. Careful patient selection with an emphasis on adequate cardiovascular function and low maintenance doses of immunosuppression at a level compatible with graft acceptance should help to prevent significant long-term morbidity. Recurrence of the original renal disease is a common histologic finding but, except in a few diseases, rarely results in graft loss. Parenthood can be a reality for most patients who have excellent graft function. PMID- 2265391 TI - Women and AIDS: a growing epidemic. PMID- 2265390 TI - Problems in the long-term renal allograft recipient. AB - Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients are still significant. Cardiovascular disease accounts for much of the mortality in long-term survivors; screening before the transplant procedure and adequate control of hypertension should help improve patient survival. Many of the gastrointestinal complications are due to overimmunosuppression and sepsis. Adequate management must include withdrawal of all immunosuppressive medications in order to save the patient's life. Liver disease is usually of viral origin; patients with chronic active hepatitis or cirrhosis should remain on dialysis. Chronic rejection is the major cause of graft loss in long-term survivors; it is unresponsive to antirejection treatment and its progression may be mediated by nonimmunologic mechanisms. Correctable problems such as renal artery stenosis and ureteral obstruction should be ruled out before a late deterioration in graft function is disregarded as chronic rejection. Post-transplant diabetes, osteonecrosis, cataracts, and nephrotoxicity are directly related to the various immunosuppressive drugs currently used. The lowest dose compatible with graft acceptance should help reduce the incidence of these nonfatal but significant complications. Recurrence of disease is a common histologic finding in many transplant recipients but, except for a few diseases such as HUS, FSGS, and oxalosis, it usually does not lead to graft failure. Successful transplantation restores fertility in many uremic patients. Adequate counseling on contraception is imperative in order to avoid unwanted pregnancies and to delay parenthood for at least 1 year. Current immunosuppressive agents are not teratogenic, no dose adjustments are necessary, and an ill-advised decrease in medication may precipitate a rejection episode. Premature delivery is the major problem in these patients and can be avoided by maintaining adequate graft function and controlling hypertension and infections. It is evident from this review that most of the long-term morbidity and mortality seen in renal allograft recipients are due to overimmunosuppression with sepsis or to side effects of the individual drugs, steroids being a common denominator in almost all cases. New immunosuppressive protocols must aim not only to improve patient and graft survival but also to avoid the many complications that limit the full rehabilitation of these patients. PMID- 2265393 TI - Innovative nursing program addresses local RN shortage. PMID- 2265392 TI - Human rights for patients in hiding. PMID- 2265394 TI - New BRN report recommends nursing shortage remedies. PMID- 2265395 TI - AIDS ethics. PMID- 2265396 TI - Psycho-social adjustment to adult onset epilepsy. A theoretical framework. PMID- 2265397 TI - Planning for the future: considering the bachelor of science in mental health. PMID- 2265398 TI - Nurse assault. PMID- 2265399 TI - The psychiatric nurse--patient advocate? PMID- 2265400 TI - Nature and role of high sister chromatid exchanges in Bloom syndrome cells. Some cytogenetic and immunological aspects. AB - The phenomenon of sister chromatid exchange (SCE) is an interesting genetic event in metaphase chromosomes, even though its exact mechanism remains unknown. The fact that SCE can take place, whether "spontaneously" or induced by various agents, is in itself important, for such an event, involving damage and possible repair of bilateral loci in chromosomes, presents opportunities for modification of the chromosomal structure and/or function (e.g., oncogene activation). It has been assumed that under "normal" circumstances, SCE does not lead to any change in the functional genome, although this may not apply to abnormal conditions. The latter may be produced by a number of chemical agents (including various carcinogens) that lead to a significantly increased incidence of SCE in normal and malignant cells either in vitro or in vivo. In fact, SCE has been recognized and advocated as a most sensitive test for potentially mutagenic and/or carcinogenic agents. Thus, the broad field of SCE studies becomes of direct interest for and subject to exploration by those involved with cancer causation and biology. In this review, a synopsis of our experiences with high SCE mechanisms in Bloom syndrome cell lines will be presented, in connection with high SCE mutant cell line derived from ataxia telangiectasia (AT) and/or malignant transformation. PMID- 2265401 TI - Transposition of the oncogene ets-1 in t(11;19) translocation in acute leukemia. AB - The specific chromosomal rearrangement t(11;19)(q23;p13) has been identified as a nonrandom chromosomal rearrangement in acute leukemia. The breakpoint, 11q23, coincides with the ets-1 oncogene locus. However, only very few studies have been done to verify the genomic alteration and transposition of ets-1 in the t(11;19) chromosomal rearrangement. In the present study, we identified the t(11;19)(q23;p13) translocation in two acute leukemic cases. One of the cases, biphenotypic leukemia, has been followed thoroughly. An abnormal karyotype was identified in the patient's blood and marrow samples at diagnosis and at relapse, while only normal karyotypes were identified at remission. In situ hybridization of chromosomal preparations with the ets-1 probe pHE5.4 resulted in silver grains nonrandomly localized to 19p13 in the metaphase spreads prepared from the blood sample taken at relapse, while no detectable grains were found on chromosome 19p13 in a sample taken at remission. To determine if genomic alterations of ets 1 are associated with this translocation, Southern blot hybridizations with the pHE5.4 probe were performed on deoxyribonucleic acid (DNA) isolated from blood or marrow samples of the patient at remission and relapse as well as on DNA from a disease-free normal control. Any DNA digested with AvaII, SstI, XbaI, and Bam HI, followed by hybridization with pHE5.4, demonstrated no genomic alterations or amplification of the ets-1 oncogene. Our study indicates that the ets-1 oncogene is transposed in the t(11;19) translocation without detectable alteration at the DNA level. The absence of ets-1 amplification in t(11;19) and its presence in the t(4,11) and t(9;11) translocations demonstrated by others suggests the possible existence of different molecular mechanisms involving the ets-1 oncogene in the pathogenesis of these leukemias. PMID- 2265402 TI - Acrocentric interconnections and NOR variants in human lymphocytes. AB - Acrocentric interconnections and NOR (nucleolus organizer region) variants are frequently observed in silver-stained metaphase preparations from lymphocytes of phenotypically normal individuals. The types of interconnections and of NOR variants are outlined. It is speculated that the satellite acrocentrics (both normal and variant) are the consequence of breakage and recoiling of these interconnections. Awareness of these two features of the human genome may facilitate understanding of the NOR/nucleolus interaction(s) in such important processes as nucleolus formation and in development and/or diagnosis of disease states (i.e., malignancy). PMID- 2265403 TI - Translocation (3;21) in a patient with secondary hematological malignancy. PMID- 2265404 TI - Chromosomal changes in thyroid tumors. Relation with DNA content, karyotypic features, and clinical data. AB - A cytogenetic study was performed in 63 thyroid tumors after a monolayer short term culture. Clonal chromosomal changes were found in 47% of carcinomas and 31% of adenomas. Chromosome 7 was altered in 40% of cytogenetically abnormal tumors. The modal DNA index measured in 26 tumors was consistent with the chromosomal mode in 88% of cases. A quantitative morphometric analysis of nuclear features differentiated between diploid thyroid adenomas with or without a single translocation, which suggests that they have different biological properties. Clonal chromosomal changes were observed in 78% of carcinomas with an aggressive behavior, but only 28% of those had no risk factors. The two patients who died early had abnormalities of chromosome 7. PMID- 2265405 TI - Acrocentric prophasing in bromodeoxyuridine-incorporated chromosomes. AB - Chromosomes that appear to be incompletely condensed [pulverized, prematurely condensed chromosomes (PCCs), prophasing] are known to occur in metaphase spreads of cells from normal individuals and more frequently in cells from individuals with malignant disease or in cells exposed in vitro or in vivo to various agents such as viruses, chemicals, and radiation. In this study involving bromodeoxyuridine (BrdU)-treated lymphocytes, a selective prophasing of acrocentrics appeared to be occurring. The acrocentrics involved were generally in interconnected groups. PMID- 2265406 TI - Why does childhood acute lymphoblastic leukemia with hyperdiploidy show a favorable prognosis? PMID- 2265407 TI - Berberine-induced morphologic differentiation and down-regulation of c-Ki-ras2 protooncogene expression in human teratocarcinoma cells. AB - A pluripotent human teratocarcinoma cell clone, NT2/D1, which was derived from the Tera-2 cell line, was induced to differentiate into cells with neuronal cell morphology by treatment with berberine. As early as 1 day after a 24-h treatment of cells with berberine at a non-toxic dose of 0.1 mg/ml in culture medium, the cells started to show morphologic changes, developing into terminally differentiated neuronal cells with long, inter-connecting network-like cellular structures. This process is much faster as compared with that induced by treatment with retinoic acid (RA), which took at least several days to develop. Unlike RA, berberine could not induce murine teratocarcinoma cell line, F9, to differentiate into endodermal cells. It was also found that, although the NT2/D1 cell clone exhibited amplification and enhanced mRNA expression of c-Ki-ras2 gene as did the parent cell line, a marked down-regulation of c-Ki-ras2 mRNA expression was observed. However, there was no change in actin mRNA expression even after differentiation had occurred. Thus, morphologic differentiation of teratocarcinoma cells into neuronal cells is found to be associated with down regulation of a protooncogene which plays some definite role in oncogenesis. The mechanism by which berberine induces differentiation in these cells needs further investigation. PMID- 2265408 TI - Enhanced lung colonization and tumorigenicity of fused cells isolated from primary MCA tumors. AB - Cells derived from cell-cell fusion events were clonally isolated from primary methylcholanthrene (MCA)-induced tumors in allophenic mice. Compared with non fused cells isolated from the same cultures, the fused cells had markedly greater experimental metastasizing (lung colonizing) activity, but only slightly greater tumorigenicity and the same cloning efficiency in soft agar. Cell-cell fusion may thus contribute to the generation of tumor heterogeneity that underlies the process of tumor progression. PMID- 2265409 TI - Chlorambucil carcinogenesis in BALB/c mice. AB - Chlorambucil, a drug used in the treatment of neoplastic and non-neoplastic disease, was administered by gavage to BALB/c mice at a dose of 1.0 mg/kg body wt. 5 times per week for 12 weeks to test its carcinogenicity. The survival was statistically reduced in treated animals of both sexes (P less than 0.001). The treatment induced a significant increase in lung tumours (males, P less than 0.001; females, P less than 0.001) and lymphoreticular system tumours (males P less than 0.01; females, P less than 0.001) in both sexes and mammary carcinomas in female mice (P less than 0.05). These results with other investigations reported in literature, suggest that chlorambucil is carcinogenic in laboratory animals, mutagenic and that it could be a potential carcinogenic hazard to man. PMID- 2265410 TI - Comparative histopathological findings in the pancreas of cigarette smokers and non-smokers. AB - Although a correlation has been suggested between cigarette smoking and pancreatic cancer, studies on pathological changes in the pancreas of smokers are fragmentary. In the present study we examined histopathologically 73 pancreases obtained by autopsy from 42 heavy cigarette smokers and 31 non-smoker patients. One invasive adenocarcinoma (2 cm in diameter) and three small carcinomas (2-5 mm in diameter) were found in smokers and one small carcinoma in a non-smoker patient. Although the incidence of pancreatic cancer in smokers was higher than in non-smokers, the difference was statistically not significant. Of smokers with pancreatic cancer, 2 had lung cancer, 1 skin cancer, 1 colon cancer and 1 was free of any malignancies. Ductal changes, including mucinous or squamous cell metaplasia and papillary hyperplasia, were found with equal frequencies in both groups of patients. The type and the incidence of these ductal alterations were not related to smoking but to the age. Our results do not indicate that cigarette smoking increases the incidence of pancreatic cancer, although, the limited number of the sections of the pancreas examined, as well as exclusion of other important variables, such as alcohol, diet and diabetes weaken the value of this study. PMID- 2265411 TI - Effects of bile acids on development of pepsinogen-altered pyloric glands in rats. AB - The effects of dietary bile acids on the development of pepsinogenaltered pyloric glands (PAPG) were examined. Male WKY/NCrj rats were given a single dose of 160 mg/kg body wt. of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gastric intubation and fed basal diet containing 0.3% sodium taurocholate (Na-TC), 0.3% sodium cholate (Na-C), 0.3% sodium glycocholate (Na-GC), 0.3% sodium tauroglycocholate, 0.3% sodium deoxycholate, 0.1% chenodeoxycholic acid or 0.5% lithocholic acid for 14 weeks. All rats also received 1 ml of saturated NaCl solution 4 times by i.g. intubation. At the end of week 16, the animals were killed, and the number of PAPG per cm of mucosal length was determined immunohistochemically. Na-TC, Na-C and Na-GC significantly increased the number of PAPG over the control value, suggesting that they may have activity to promote gastric carcinogenesis. PMID- 2265412 TI - Inhibition of mouse skin tumor promotion by adriamycin and daunomycin in combination with verapamil or palmitoylcarnitine. AB - The anti-cancer drugs Adriamycin (ADR) and Daunomycin (DAU) alone were unable to inhibit the promotion of skin papillomas by repeated applications of 8.5 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA) in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated mice. Pretreatments with 50 micrograms of ADR also failed to alter the tumor-promoting activities of smaller doses of TPA. Therefore, the effects of the anthracycline antibiotics on skin tumor promotion were evaluated in combination with the Ca2+ antagonist verapamil (VRP) and the protein kinase C (PKC) inhibitor palmitoylcarnitine (PC), compounds known to circumvent drug resistance. When applied simultaneously with each promotion treatment with 8.5 nmol of TPA, 2.5 mg of VRP inhibited the number of papillomas/mouse by 26%. But the combination of VRP + 50 micrograms of ADR or DAU inhibited the yields of papillomas by 50 or 47%, respectively, suggesting that VRP was required to reveal the antitumor-promoting activities of otherwise ineffective drugs. Similarly, the promotion of skin tumors by TPA was inhibited synergistically by the combinations of 2 mumol of PC + 50 micrograms of ADR or DAU. For instance, ADR and DAU had no effects alone but inhibited the incidence of skin papillomas by 78 and 86%, respectively, in the presence of PC, a compound which alone inhibited the tumor incidence by only 44%. The results indicate that ADR and DAU are effective against the promoting component of skin carcinogenesis only if they are applied in combination with Ca2+ antagonists or PKC inhibitors at a time when they can inhibit the early biochemical effects induced by TPA. PMID- 2265413 TI - Effect of bis(bilato)-1,2-cyclohexanediammineplatinum(II) complexes on lung metastasis of B16-F10 melanoma cells in mice. AB - New platinum(II) complexes, bis(bilato)-1,2-cyclohexanediammineplatinum(II) which were lipophilic and water-miscible, were tested for antitumor activity against lung nodules from intravenously injected B16-F10 melanoma cells in C57BL/6 mice by intravenous administration of the complexes in water suspension form. Among them, DACHP(litho)2 and DACHP(urso)2 had high antitumor activity but others had no activity. The antitumor activity of DACHP(urso)2 was increased significantly by injecting it three times; T/C was over 280% with 100-day survivors of 3 of 6 mice tested. Large amounts of total platinum were found in lung and liver tissues by atomic absorption spectroscopy after single intravenous injection of DACHP(urso)2 suspension in ICR mice. PMID- 2265414 TI - 1 Alpha-hydroxyvitamin D3 suppresses colonic tumorigenesis induced by repetitive intrarectal injection of N-methyl-N-nitrosourea in rats. AB - The effect of 1 alpha-hydroxyvitamin D3 (1 alpha (OH)D3) on colonic tumorigenesis induced by chronic treatment with N-methyl-N-nitrosourea (MNU) was studied in rats. Seventy-four female F344 rats received an intrarectal injection of 1 mg of MNU once a week for 40 weeks. Two-thirds of rats were given concomitant administration of 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha (OH)D3 through an intragastric route thrice weekly. Numbers of rats bearing colonic tumor were 21 in MNU alone (n = 24), 17 in MNU + MCT (n = 25) and 12 in MNU + 1 alpha (OH)D3 group (n = 25) (uncorrected chi 2 = 8.72). The result indicated that colonic tumorigenesis induced by the chronic treatment with MNU was suppressed by oral supplementation of 1 alpha (OH)D3 and the inhibitory effect of 1 alpha (OH)D3 was partly due to the effect of MCT. PMID- 2265415 TI - O6-alkylguanine-DNA alkyltransferase activity in human brain tumors. AB - The O6-alkylguanine-DNA alkyltransferase (AT) activity in different kinds of human brain tumors was investigated. Twenty-seven brain tumors were analysed. Twenty-five of them showed proficient AT activity with values ranging between 20 and 722 fmol AT/mg protein. The two AT-deficient tumors observed were an oligodendroglioma and an astrocytoma. The relationship between the different histological kinds of tumor, with respect to the AT activity was: meningeomas greater than sarcomas greater than glioblastomas greater than astrocytomas greater than oligodendrogliomas greater than neurinomas greater than lymphomas. The proposal of Kohn (DNA filter elution methods in anticancer drug development. In: Concepts, Clinical Developments, and Therapeutic Advances in Cancer Chemotherapy. Editor: F.M. Muggia. Martinus Nijhoff Publishers, Boston) to confine treatments with alkylating antineoplastic agents to AT-deficient tumors, is discussed. PMID- 2265416 TI - Additive interaction between tamoxifen and rifampicin in human biliary tract carcinoma cells. AB - A novel two-drug combination of tamoxifen and rifampicin has been investigated for the treatment of biliary tract-associated malignancies. Their effects, alone and in combination, on human tumour cells were studied using two pancreatic carcinoma cell lines. MIA PaCa-2 and AsPC-1, and a gall bladder carcinoma cell line, G-415. Inhibition of growth was used as an endpoint. The cells differed in sensitivity to equimolar doses of the two drugs given as single agents. Combined doses of rifampicin and tamoxifen resulted in growth inhibition to an extent that was suggestive of additive or synergistic drug effects. More detailed analysis was carried out, involving the production of an 'envelope of additivity' for each cell line. An additive effect of drug combination was shown to occur in all three cell lines, thus providing a basis for use of this novel two-drug combination in the treatment of biliary tract-associated malignancies. PMID- 2265417 TI - Effect of breast cyst fluid on oestrogen 17-oxidoreductase activity in MCF-7 breast cancer cells. AB - Breast cyst fluid (BCF) was found to stimulate oestrogen 17-oxidoreductase activity in the reductive direction, i.e., conversion of oestrone (E1) to oestradiol (E2), in MCF-7 breast cancer cells. Dialysis of BCF revealed that this property of BCF was present in both dialysed BCF and dialysate, implying that both high and low mol. wt. substances were responsible for stimulating E1 to E2 conversion. Gel filtration of dialysed BCF revealed that the high mol. wt. substances responsible for the stimulation of E1 to E2 conversion had mol. wts. of approximately 11 kD and 68 kD. This property of BCF would serve to increase the concentration of E2, a steroid which may play a role in mammary carcinogenesis. PMID- 2265418 TI - Effect of cigarette smoke inhalation on benzo[a]pyrene-induced lung carcinogenesis in vitamin A deficiency in the rat. AB - Vitamin A deficiency caused a significant increase (P less than 0.05) in benzo[a]pyrene (BP)-induced lung tumor incidence and tumor burden in male Wistar rats. Inhalation of cigarette smoke during initiation and post-initiation phases of carcinogenesis resulted in higher tumor burden as compared to the same observed in the animals exposed to cigarette smoke during the post-initiation phase only. Stimulation in tumor burden by cigarette smoke was increased further by vitamin A deficiency. PMID- 2265419 TI - Effects of nutritional folate deficiency on the adhesive properties of murine melanoma cells. AB - Folate deficient murine B16 melanoma cells adhered more rapidly and in higher percentages to plastic plates or dishes coated with laminin or fibronectin than folate replete cells. These changes in the adhesive properties of murine melanoma cells induced by nutritional folate deficiency were not mediated by changes in cell size, proliferative capacity or cell cycle distribution. While melanoma cells served as a suitable surface for prothrombinase complex formation, folate deficiency did not alter this membrane function, suggesting that the membrane changes associated with folate deficiency are relatively specific. PMID- 2265420 TI - The effectiveness initiative: impact on the Colorado nurse. PMID- 2265421 TI - [Perspectives in sports medicine in Czechoslovakia]. AB - Evidence has been provided that adequate physical activity prevents diseases caused by hypokinesia (hyperlipoproteinaemia, ischaemic heart disease, myocardial infarction, obesity and to a certain extent also hypertension) and that it retards the ageing process, in particular osteoporosis. It prolongs thus active life and life in general. The majority of our population suffers from lack of exercise. It is therefore necessary to promote activity and sports not only in healthy young people (in particular with a sedentary occupation) but also in older people. And in the latter group in particular in those with a mild degree of ischaemic heart disease, mild hypertension, in obese subjects, diabetics and those who come from families where these diseases occur. Even when the disease is already advanced or a relapse is imminent, a certain amount of physical activity, controlled by sports doctors on agreement with the attending physician is indicated. Sports Consulting clinics, since the foundation of the first one in 1924, served all sportsmen and visitors. During the totalitarian regime district and regional departments of sports medicine were established as well as an Institute of National Health for top sports but their activities were restricted only to contesting sportsmen and professionals. During the foreseen reorganization of health care the care of sports doctors most be extended to comprise also the above mentioned groups of non-contesting people and subjects at risk. This will be possible only if sports medicine will be included in primary health care and if eventually a department of sports medicine will be established in every institute of national health. It will serve not only sportsmen but the public as a whole. PMID- 2265422 TI - [Surveillance of tuberculosis in the Czech Republic in 1989]. AB - The authors report on the tuberculosis situation in the Czech Republic (CR) in 1989 and compare the data with 1988. The incidence of all cases of TB was 18.4/100,000, the incidence of all cases of respiratory TB 15.5 and that of bacteriologically confirmed cases 11.1/100,000. The mortality from TB was also low (1/100,000). Two-thirds of the patients were detected because of the patients' complaints. This passive screening was, however, inadequate in subjects with a poor health consciousness. Active screening was restricted to subjects with a high risk of TB (in contact with tuberculosis, with different diseases, with socio-economic factors, migrating subjects, non-cooperating subjects). In 1989 for the first time in the CR stagnation of the incidence of bacteriologically confirmed TB of the respiratory organs was recorded. The number of patients (5.7/100,000) with TB with a microscopically positive bacteriological finding in sputum was also the same. A slowing down of the hitherto recorded favourable trend of TB must be foreseen. It will be important to maintain the contemporary system of TB surveillance. PMID- 2265423 TI - [Detection of atrial and ventricular ectopic activity in a health population]. AB - Using a system which makes it possible to monitor continually in the course of 24 hours the electrocardiogram, the authors examined 50 medical students aged 18-24 years. In all subjects a sinus rhythm was recorded, frequently combined with sinus, respiratory arrhythmia. The mean heart rate during the investigation period varied between 61-69 strokes per minute. A maximum heart rate between 117 and 200 strokes per minute was always conditioned by physical exertion. Isolated supraventricular extrasystoles were recorded in 34% of the examined subjects and were more frequent in women than in men. Isolated ventricular extrasystoles were recorded in 32% of the examined subjects and were more frequent in men than in women. Conduction time on the electrocardiogram at rest and during long-term monitoring were normal in all the examined subjects. PMID- 2265424 TI - [Decreasing the occurrence of arrhythmia during coronary spasm by the early administration of nitrates]. AB - Variant angina is frequently accompanied by serious arrhythmias. The aim of our study was to verify the role of early nitrate administration in prevention of these arrhythmias. We compared arrhythmias occurrence in the course of 104 episodes of chest pain with ST elevation during which short acting nitrate was not administered (group I) and 114 episodes with administration of 2.5 mg isosorbit dinitrate (ISDN) spray (group II). Serious arrhythmias occurred in spontaneous episodes in 41 cases (39%) and in episodes with early ISDN administration in 15 cases (13%). Particular types of arrhythmias were as follows: ventricular premature beats in group I 32 and in group II only 12, supraventricular premature beats 4, resp. 3, A-V block IInd or IIIrd degree 5, resp. 1, ventricular tachycardia 5, resp. 0, junctional bradycardia 0, resp. 1. In conclusion, early administration of nitrates at the very beginning of stenocardia during coronary spasm can prevent or reduce the occurrence of serious arrhythmias. PMID- 2265425 TI - [Estimation of systolic pressure in the right ventricle (pulmonary artery) using Doppler and its importance in the detection of pulmonary hypertension]. AB - Using the pulsed Doppler system with a high reparative frequency (HPRF), the authors made within 1 hour and 3 days after diagnostic right-sided catheterization 38 measurements of the trans-tricuspid pressure gradient in 31 consecutive patients. To the gradient calculated from the absolute velocity of flow through the jet of tricuspid regurgitation the authors added two different arbitrarily determined pressure values in the right atrium to obtain the systolic pressure in the right ventricle--RVSP (which assuming the absence of an obstruction between the right ventricle and pulmonary artery equals the systolic pressure in this artery). The calculated RVSP from the Doppler assessment correlated highly significantly with the directly manometrically obtained values of the same indicator (r = 0.973; p less than 0.001). An even closer correlation was obtained when using a differentiated estimate of the pressure in the right atrium/according to the filling of the jugular veins) (r = 0.977; p less than 0.001). From the RVSP values the authors tried to predict the presence of pulmonary hypertension (PH) diagnosed from the median pressure in the pulmonary artery (PAP greater than or equal to 20 mm Hg which was considered conclusive). Using the arbitrarily assessed range of systolic PH greater than 35 mm Hg, the sensitivity of the ultrasonographic estimate was 79% with a 60% specificity, while when the criterium of greater than 40 mm Hg was used, the corresponding values were 64% and 90%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265426 TI - [Physician-martyrs of the Czech resistance during World War II. VI]. PMID- 2265427 TI - Calcium currents in normal and dystrophic human skeletal muscle cells in culture. AB - Human muscle cells obtained from biopsy specimens were grown in a primary culture system and electrophysiologically studied. Whole cell patch-clamp recordings revealed the presence of two types of calcium currents: (i) a low-threshold (-60 mV) one (ICa, T) with fast activation and inactivation kinetics (time-to-peak: 39 ms at -30 mV); and (ii) a high-threshold (-10 mV) one (ICa,L) with slower kinetics (time-to-peak: 550 ms at 20 mV). These two types of calcium currents could be also distinguished by their pharmacological characteristics since ICa,L was sensitive to the antagonist and agonist dihydropyridine derivatives contrary to ICa,T which was completely resistant to these compounds. These functional calcium channels existed both in normal and Duchenne dystrophic (DMD) human skeletal muscle cells in culture. We discuss a possible role of these two types of calcium channels in the myoplasmic calcium accumulation observed in the Duchenne muscular dystrophy. PMID- 2265428 TI - Transient increases of intracellular Ca2+ induced by volatile anesthetics in rat hepatocytes. AB - The affects of volatile anesthetics on mobilization of intracellular Ca2+ was monitored in primary cultures of rat hepatocytes using the fluorescent Ca2+ probe Fura-2. The use of Fura-2 was limited by several factors which complicated the quantitative analysis of the results, such as: (i) a high rate of dye leakage; (ii) changes in the redox state of the hepatocytes which interfered with the fluorescence produced by the dye at various excitation wavelengths; (iii) compartmentalization of the dye producing high local intracellular concentrations; and, of particular importance for this study, (iv) enhanced photobleaching of the dye in the presence of halothane. To aid in the interpretation of the Fura-2 data, the Ca2(+)-sensitive photoprotein aequorin was also used to monitor changes in [Ca2+]i. The aequorin and Fura-2 techniques qualitatively yielded the same result, that the volatile anesthetic agents halothane, enflurane, and isoflurane induce an immediate and transient increase of [Ca2+]i. The durations of these transients were approximately between 5 and 10 min and were not related to any evident acute cell toxicity. The [Ca2+]i increases induced by the volatile anesthetic agents were dose-dependent, with halothane the most potent. The exact mechanism governing these increases in [Ca2+]i induced by these anesthetics in rat hepatocytes is unknown, but is likely to involve effects on both the cell surface membrane and endoplasmic reticulum components of the signal transducing system. PMID- 2265429 TI - Immunohistochemical study of neuropeptide Y-containing nerve fibers in the human clitoris and penis. AB - The occurrence and distribution of neuropeptide Y in the human clitoris and penis was investigated by light immunohistochemistry. Neuropeptide Y-containing nerve fibers were detected in the tunicae of arteries and veins as well as among trabecular smooth muscle. The distribution pattern of the peptide was similar in both organs although a higher density of immunoreactive nerve fibers was detected in the penis. The immunolocalization of neuropeptide Y was also compared with that of neuron-specific enolase, a neuronal marker which labels the entire nerve network. It is suggested that neuropeptide Y is involved in the physiology of the penis and the clitoris, affecting vascular and nonvascular smooth muscle activity. PMID- 2265430 TI - The effect of transforming growth factor-beta on the alkaline phosphatase activity in rabbit renal cortical tubular cell cultures. AB - The effect of various growth regulators including epidermal growth factor and transforming growth factor-beta on the alkaline phosphatase activity of rabbit renal cortical tubular cells has been investigated in a serum-free culture. As a result, it was found that transforming growth factor-beta, known to be a growth inhibitor of renal tubular cells, increased the alkaline phosphatase activity of the tubular cells dose-dependently and that cycloheximide blocked any increase in the activity of this factor. In contrast, epidermal growth factor decreased the alkaline phosphatase activity in the tubular cells. PMID- 2265431 TI - Effects of 17 beta-estradiol on c-myc and c-Ha-ras expression in the liver of ovariectomized female rats. AB - Twenty four hours after i.p. injection of 17 beta-estradiol (E2) (500 micrograms/100 g b.w.) to ovariectomized rats, the hepatocytes [3H]-thymidine pulse-labeling index (L.I.) was significantly increased, reaching a value of 4.3 +/- 1.6 percent (i.e. much lower than 32.0 +/- 2.0 percent 24 h. after partial hepatectomy -PH-). E2-treatment was followed by an increase in liver content in c myc transcripts, with a peak at 650 percent basal value at 8 h, very similar to that observed after PH. In contrast, E2 induced an increase in liver c-Ha-ras expression with a similar time-course evolution but markedly lower amplitude than that seen after PH. These data are consistent with a role of c-myc in proliferative competence i.e. the ability to perform the Go-G1 transition, and with a role of c-ras in further progression of the cells in the cycle. PMID- 2265433 TI - Knee bracing. PMID- 2265432 TI - The history and classification of knee braces. AB - There has been a great deal of concern within the orthopedic community regarding the lack of objective data available on the multitude of knee braces flooding the marketplace. This article hopes to fill that void by presenting an overview of the history and classification of knee braces. PMID- 2265434 TI - Choosing functional knee braces. AB - Choosing a functional brace for knee injury is a complex issue complicated by a lack of quantitative research on the subject and an increasing number of braces currently on the market. The correct brace decision will be facilitated by a better understanding of knee injury biomechanics and by a thorough understanding of the choices available. The ultimate selection of a brace should be based on sound mechanical criteria and individualized for each patient. The brace must be mechanically effectual and one the patient likes, has confidence in, and will tolerate. In combination with aggressive rehabilitation, the functional brace can make a significant contribution to returning individuals to functional activity. PMID- 2265435 TI - Laboratory evaluation of prophylactic knee brace performance under dynamic valgus loading using a surrogate leg model. AB - Because of contradictory data accumulating from on-field trials of prophylactic knee braces, benchtop laboratory studies of brace performance have become important. This study (1) describes design considerations for a mechanical leg surrogate developed for prophylactic brace testing, (2) validates surrogate performance under dynamic lateral loading, and (3) reports comparative performance data for eight commercial knee braces tested using this surrogate system. PMID- 2265436 TI - Postoperative knee bracing. PMID- 2265437 TI - Functional analysis of anterior cruciate ligament braces. AB - Whether or not anterior cruciate ligament (ACL) braces work has been the subject of some debate. Research efforts undertaken to understand these braces have been divided into two fronts: static and functional analysis. This article explores those issues surrounding the functional analysis of ACL braces. PMID- 2265438 TI - The use of knee braces during rehabilitation. AB - This article has profiled the use of knee braces as an augmentation to the overall rehabilitation program following knee injury. It has also outlined other aspects of rehabilitation, the use of continuous passive motion devices, and other forms of exercises and training that, together with bracing, may enhance patient recovery. Continuous passive motion devices have been used for many different orthopedic problems with good success. Understanding the mechanics of how these devices move the knee and the forces that can be applied to the knee is helpful in deciding on their use after ligamentous reconstructions. Rehabilitation of the knee following surgery requires a good understanding of the effects that each exercise has on the knee and the reconstruction. Gradual progression of exercises to the knee following knee ligament reconstruction will not overstress healing tissues. Many different types of knee braces exist, and careful evaluation of them may enhance patient recovery. PMID- 2265439 TI - Bracing for patellar instability. AB - Knee pain secondary to problems with patellar tracking is common. The initial treatment for these problems is conservative. Patellar orthotics have been used extensively to treat a variety of extensor mechanism problems. Millions of health care dollars are spent annually on the use of these braces. There are many different patellar orthotics on the market today. The use and design of most of these devices are unclear and often lack a solid biomechanical foundation. The practical mechanical function of these braces is to reduce the lateral displacement of abnormal patellofemoral tracking. Orthotics that are designed and tested using practical biomechanical principles for applying a medially directed force to the patella seem to have a role in treating patients with knee pain secondary to patellar malalignment and instability. Well-defined and controlled clinical studies of the use of patellar braces are lacking. PMID- 2265441 TI - The effect of bracing on the collateral ligaments of the knee. AB - Disruption of the ligamentous structures of the knee is commonly seen in competitive sports. The role of prophylactic and functional bracing is controversial. Currently, prophylactic bracing has not been shown, conclusively, to be protective. Functional braces appear to have a capacity to provide some protective effect. PMID- 2265440 TI - In vitro assessment of prophylactic knee brace function. AB - In an attempt to evaluate the effectiveness of prophylactic knee bracing and to determine the influence of brace design and material characteristics on the protection of knee ligaments, a series of biomechanical studies were completed. The first series of tests were preliminary parametric tests of brace function utilizing cadaver limbs to understand the failure biomechanics of the medial restraints during low- and high-rate valgus-producing knee trauma. Static and dynamic mechanical properties of the braces were also studied. Finally, a limited series of brace/cadaver knee low-rate loading response tests were performed. With the information obtained from preliminary testing, an instrumented surrogate knee was developed and validated for lateral impact responses. The surrogate allowed for the measurement of ligament force time response during a controlled impact. Special impact facilities were constructed to allow the measurement and control of impact momentum. The effectiveness of six different prophylactic braces in preventing MCL and ACL injury was evaluated using the surrogate and impact facility. Impact parameters of mass, velocity, knee flexion angle, and limb restraint were varied to simulate different direct lateral impact conditions of game play. Testing results were normalized and expressed as an impact safety factor to allow for comparison of braces. An ISF of 1.5 (representing a ligament force reduction of 30%) was arbitrarily chosen as the minimum standard for brace performance. The majority of prophylactic knee braces tested proved to be biomechanically inadequate for protecting the MCl from a direct lateral impact. A few, however, appear to protect the ACL preferentially. In the case of a controlled, direct lateral blow, all but a few braces tested provided some beneficial protection to the MCL and ACL, but performed well below the standard 1.5 ISF level. Therefore, based on the biomechanical research, it is our opinion that the concept of prophylactic lateral knee bracing can be effective. We recommend that prophylactic braces not be abandoned, but rather improved, biomechanically validated, and further evaluated through well-controlled prospective clinical studies. PMID- 2265442 TI - Clinical significance and evaluation of prophylactic knee brace studies in football. AB - A review of nine studies of prophylactic knee braces in American tackle football found some support for the use of double-hinge braces in high school but little support for their use at the collegiate level. Problems with bias and confounding make it necessary that caution be exercised in the interpretation of the results of these studies, however,. To which groups these results might apply must also be considered. The two studies that assigned braces randomly found lower injury rates among high school and high-school-sized players for knee injuries and knee ligament injuries. Conversely a large, multiteam collegiate study found a significantly higher rate of knee injuries among brace users, a difference that remained when controlled for position, skill, and previous injury. PMID- 2265443 TI - [Spinal cord regulation of somatic functions in mammals]. PMID- 2265444 TI - [Stochastic models of spontaneous neuronal activity]. PMID- 2265445 TI - [The importance of smooth muscle cell cultures for understanding the physiology and pathophysiology of vascular walls]. PMID- 2265446 TI - [Structure, function and significance of glucocorticoid receptors]. PMID- 2265447 TI - [Biochemical function and metabolism of vitamin C in animals]. PMID- 2265448 TI - A microcomputer program for evaluating evoked neuronal unit activity. PMID- 2265449 TI - Update: progress toward eradicating poliomyelitis from the Americas. PMID- 2265450 TI - Salmonellosis outbreak--Alberta. PMID- 2265451 TI - Nosocomial transmission of hepatitis B virus associated with a spring-loaded fingerstick device--United States. PMID- 2265452 TI - Differential effect of 6-ethylmercaptopurine on c-myc expression in wild-type and HGPRT-deficient HL-60 cells. AB - A variety of compounds inhibit the growth and induce differentiation of human promyelocytic leukemia (HL-60) cells. HL-60 subclones that lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) can also be induced to differentiate with purine analogs. Mechanisms by which purine analogs induce differentiation offer unique possibilities for cancer chemotherapy. We have studied the effect of the purine analog 6-ethylmercaptopurine (e6MP) on the growth and induction of differentiation in both wild-type and HGPRT-deficient HL 60 cells. We have previously shown that e6MP inhibits cell growth in both wild type and HGPRT-deficient HL-60 cells without activation through salvage pathways. In this report we evaluate the effect of e6MP on c-myc mRNA expression. c-Myc mRNA, which is amplified in HL-60 cells, has been shown to play a role in the induction of granulocytic differentiation in HL-60 cells. e6MP transiently down regulates c-myc mRNA in wild-type cells but has no effect on c-myc mRNA expression in HGPRT-deficient HL-60 cells. Despite the differential effects of e6MP on c-myc mRNA, both wild-type and HGPRT-deficient HL-60 cells appear to engage in terminal differentiation. The morphological changes and nonspecific esterase activity induced by e6MP suggest differentiation down the monocytic pathway. However, early monocytic markers such as the rapid induction of c-fos and the stabilization of c-fms mRNA are not observed. In addition, e6MP inhibits TPA-induced monocytic/macrophage differentiation as characterized by stabilization of c-fms mRNA and cellular adherence. PMID- 2265453 TI - Celiptium-induced nephrotoxicity and lipid peroxidation in rat renal cortex. AB - The antitumor drug celiptium, or N2-methyl-9-hydroxyellipticinium (NMHE), is an ellipticine derivative used in the treatment of breast cancer. Celiptium-induced dose-dependent renal toxicity in rats is characterized by tubular necrosis, tubulo-interstitial lesions and lipid overload in proximal tubular cells. Since biooxidative activation of celiptium occurs in kidney via highly electrophilic intermediates, we studied the effects of celiptium on rat renal cortex lipids in the context of lipid peroxidation damage. Female Wistar rats were injected with a single i.v. dose of 20 mg/kg celiptium and were killed on day 2, 4 or 8. Histochemical analysis of kidney sections detected Oil Red O (ORO)-positive deposits, whereas the same sections studied using Holczinger's copper rubeanic acid method showed free fatty acid (FFA) granules in renal tubular cells of celiptium-treated rats. Electron microscopy revealed large fatty droplets in proximal tubular cells. As creatinine clearance decreased on days 4 and 8, celiptium induced a significant increase in renal cortex FFA levels (6-fold increase over pretreatment values on day 8), whereas total glycerides increased 1.5 times. A 15% decrease in total phospholipids (PL) and a 50% decline in the mass of phosphatidylethanolamine (PE) were detected by lipid phosphorus assay. A 1.2-fold decrease in the unsaturation index of total PL was noted, with a significant decline in arachidonic acid (20:4). A 15% decrease in arachidonic content was observed in the fatty acid composition of PE. Analysis of the fatty acid composition of neutral lipids showed changes only in the FFA class. A great proportion of oleic (18:1) and linoleic (18:2) acids was found. Iodometric titration and thiobarbituric acid (TBA) reactivity detected respectively significant amounts of lipid hydroperoxides and TBA-reactive material in renal cortex lipid extracts on days 2, 4 and 8. The lipid-peroxidation process appeared to be involved in the pathogenesis of celiptium nephrotoxicity. PMID- 2265454 TI - Porfiromycin disposition in oxygen-modulated P388 cells. AB - The cytotoxicity, metabolism, and DNA alkylation of porfiromycin (PFM) under aerobic and hypoxic conditions were evaluated in P388 murine leukemia cells. Clonogenic assays showed that the IC50 value for a 1-h exposure to PFM was 4 microM for aerobic cells and 0.5 microM for hypoxic cells. After a 1-h exposure to concentrations of 1, 5, and 10 microM [14C]-PFM, the accumulation of total radioactivity in hypoxic cells was 10 to 20 times that in aerobic cells. The disposition of radioactivity in cells that had been treated for 1 h with 5 microM PFM under aerobic or hypoxic conditions showed that (a) under either condition, internal free-PFM concentration equalled the external drug concentration; (b) DNA , RNA-, and protein-bound radioactivity were at least 10 times greater in hypoxic cells than in aerobic cells; and (c) known metabolites and unidentified radioactive products were also generated in greater amounts in hypoxic cells than in aerobic cells. Thus, the increased amounts of radioactivity accumulated by hypoxic P388 cells after exposure to [14C]-PFM resulted from the accumulation of nonexchangeable protein and nucleic-acid adducts and metabolites rather than free PFM. Determinations of DNA adducts formed in P388 cells revealed five possible adducts: (1) N2-(2'-deoxyguanosyl)-7-methylaminomitosene, (2) a second monofunctional PFM-guanine adduct, (3) a PFM cross-linked dinucleotide, (4) possibly a nucleoprotein-related adduct, and (5) an unknown. We conclude that the enhancement of PFM-induced cytotoxicity by hypoxia appears to be primarily due to increased alkylation of macromolecules. PMID- 2265455 TI - Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation. AB - The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for greater than 20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4 11.8) for VP-16 and 3.4 (2.5-4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6-10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo. PMID- 2265456 TI - Metabolism and elimination of rhodamine 123 in the rat. AB - Little is known of the pharmacology of rhodamine 123 (RH-123), an agent reported to have carcinoma-selective experimental antitumor activity. Accordingly, using a high-performance liquid chromatographic assay system with fluorescence detection, we examined the plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose (5 mg/kg) equivalent to the therapeutic dose used in murine tumor models. Following drug administration to unconscious animals, plasma levels of drug-associated fluorescence fell in a triphasic manner (t1/2 alpha, 15 min; t1/2 beta, 1 h; t1/2 gamma, 4.7 h). In plasma, unchanged drug predominated but lower levels of the deacylated metabolite rhodamine 110 (RH-110) and two unknowns were also detectable throughout the study. Drug fluorescence was recovered extensively in both urine and bile. In unconscious animals with ureteral cannulae, urinary excretion (11.4% of the dose in 6 h) occurred predominantly as unchanged RH-123 (97% of the total), with low levels of RH-110 (2.4%) and two unknowns (less than 0.6% combined) also being present. Similarly dosed conscious animals (without surgical intervention) housed in metabolic cages showed a comparable pattern of urinary excretion, with 11.9% of the drug dose being recovered in 6 h and 21.9%, by 48 h. Biliary drug elimination accounted for 8% of the delivered dose in 6 h in unconscious animals and for 11% by 36 h in conscious animals fitted with biliary cannulae. In contrast to urinary excretion, in which unchanged drug predominated, only 50% of the fluorescence recovered in bile was attributable to RH-123. The remainder was due to a number of products that were detectable throughout the study. Of these, one present at significant levels was identified as a glucuronide conjugate of RH-123, based on the liberation of parent drug when the purified metabolite was incubated with beta-glucuronidase or hydrolyzed with 1 N hydrochloric acid. Further studies with a radiolabeled form of RH-123 are necessary to establish the identity of the remaining unknowns disclosed in this work. PMID- 2265457 TI - Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig. AB - Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to approximately 90, approximately 120 and approximately 150 mg/m2) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [99 mTc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically, and GFR and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with greater than or equal to 2 mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S1 portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GFR and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was less than 50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically "silent" until exposure to an additional nephrotoxic insult. PMID- 2265458 TI - Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters. AB - Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time. PMID- 2265459 TI - The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity. AB - Anticonvulsants are commonly used empirically to prevent seizures in patients receiving high-dose busulfan in preparation for bone marrow transplantation. This study evaluates the effects of two anticonvulsants with enzyme-inductive properties, phenytoin and phenobarbital, and an enzyme inducer without anticonvulsant properties, Aroclor 1254, on the myelotoxicity and acute neurotoxicity of busulfan in a murine model. To assess the neuroprotective effects of these agents, we studied the effects of a single dose of 100 mg/kg i.p. busulfan, previously shown in this model to be uniformly lethal due to neurotoxicity. A significantly greater proportion of mice survived when pretreated with phenytoin or phenobarbital as compared with Aroclor 1254 pretreatment or an untreated control group. Busulfan myelotoxicity was studied in another group of mice treated with 135-150 mg/kg given in divided doses over 6 days. The proportion of animals surviving the otherwise myeloablative effects of this regimen were significantly improved by Aroclor 1254, high-dose phenytoin, and phenobarbital pretreatment. We conclude that anticonvulsants offer protection from the acute neurotoxicity of busulfan. However, these enzyme-inducing agents may reduce the myelosuppressive effects as well. These results suggest that an inducible enzyme system such as microsomal or glutathione S-transferases plays an important role in busulfan metabolism, warranting concern over concomitant administration of agents that either induce or inhibit these enzymes. PMID- 2265460 TI - Carboplatin and etoposide in advanced lung cancer:--a phase I study. AB - This phase I study was carried out to determine the maximal tolerated dose of carboplatin (Car) together with a fixed dose of etoposide (E) and to recommend the optimal dose for a phase II study. The dose of E was 100 mg/m2 given i.v. on days 1-3, and the starting dose of Car was 200 mg/m2 given i.v. on day 1. The dose was escalated until WHO grade 4 toxicity developed after two treatment cycles in more than one-third of the patients. A total of 33 patients with advanced lung cancer entered the trial. The maximal tolerated toxicity of the combination was reached at a dose of 500 mg/m2 Car. Myelosuppression was moderate, and hematological toxicity of WHO grade 4 was encountered in one of five patients at 475 mg/m2 and in two out of five patients at 500 mg/m2. The main toxic effects were leucopenia and thrombocytopenia. The frequency of treatment related infections was low and no deaths were caused by treatment. There was a significant overall correlation between the platelet nadir and creatinine clearance. One complete response and three partial responses were achieved after two treatment cycles. Based on the results of the present study, the dose of carboplatin (combined with 100 mg/m2 eposide given on days 1-3) recommended for phase II studies is 450 mg/m2. PMID- 2265461 TI - Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B. AB - Carboplatin (400 mg/m2) was given at 28-day intervals to 41 patients with malignant mesothelioma. In all, 40 patients were eligible and evaluable for response. Partial responses were seen in 2 cases (5%); regression of evaluable disease, in 1 patient (2%); and stable disease, in 19 subjects (48%). A median of two doses of carboplatin per patient resulted in mild toxicity. Leukopenia (less than or equal to 2,000 cells/microliters) and thrombocytopenia (less than 100,000 cells/microliters) were seen in only 6% and 20% of the patients, respectively. Median survival from study entry was estimated at 7.1 months, with a 1-year survival of 25% +/- 7%. Carboplatin given at a dose of 400 mg/m2 at 28-day intervals shows minor activity against malignant mesothelioma. PMID- 2265463 TI - The conversion stage of skin carcinogenesis. PMID- 2265462 TI - DNA binding of iproplatin and its divalent metabolite cis-dichloro-bis isopropylamine platinum (II). AB - The quadrivalent second-generation platinum complex iproplatin and an in vivo divalent metabolite of iproplatin, cis-dichloro-bis-isopropylamine platinum (CIP) were tested for binding to DNA in vitro. DNA binding was determined according to radioactivity measured using [14C]-iproplatin and [14C]-CIP and also by platinum content. Results indicate that (a) iproplatin shows negligible binding to DNA, (b) CIP binds to DNA in a time-dependent fashion, and (c) the isopropylamine ligand is intact when CIP is bound to DNA. Glutathione (GSH) inhibits the binding of CIP to DNA, possibly by inhibiting binding to DNA of the aquated form of CIP. PMID- 2265464 TI - Effects of a high fat diet on liver DNA methylation in rats exposed to N nitrosodimethylamine. AB - Previous experiments have shown that a high fat diet changes incidence and tumour sites by N-nitroso-dialkylamines. The purpose of this study was to examine the effect of high and low fat diet on DNA methylation 6 weeks after the end of a chronic N-nitrosodimethylamine (NDMA) exposure (total dose 150 mg/kg). The concentration of O6-methyldeoxyguanosine (O6-MedG) in liver DNA was measured by immunoassays. The level of O6-MedG persisted 6 weeks after the last dose of NDMA and was 6-fold higher (P less than 0.05) in animals on high fat as compared to low fat diet. In another experiment, in which rats on a low and high fat diet received a single NDMA dose (2 mg/kg), the time-dependent removal of O6-MedG from liver and the hepatic O6-methylguanine DNA-alkyltransferase activity was not modified by the type of diet. These results indicate that a high fat diet enhances DNA methylation in the liver, after chronic treatment by NDMA, and that this effect is likely to be responsible for an increased incidence of liver haemangiosarcomas. PMID- 2265465 TI - Effect of polyamine oxidase inhibition on the colonic malignant transformation process induced by 1,2-dimethylhydrazine. AB - Recent studies of colon adenocarcinomas in humans and experimentally induced colonic tumors in rodents have demonstrated selective elevations in the level of N1-acetylspermidine in these malignant tissues. The exact relationship of these alterations in acetylated polyamine levels to the malignant transformation process, however, remains unclear. In order to clarify this issue, rats were given s.c. injections of 1,2-dimethylhydrazine (DMH; 20 mg/kg body wt/week) or diluent for up to 26 weeks. After 10 weeks of carcinogen treatment, one-half of the animals in each group were also concomitantly given i.p. injections of MDL 72527 (20 mg/kg body wt/week), a specific inhibitor of polyamine oxidase, until they were killed. Animals were killed after 15 weeks of DMH treatment and polyamine levels as well as the activities of polyamine oxidase, ornithine decarboxylase and spermidine-N1-acetyltransferase were measured and compared in rat proximal and distal colonic mucosa of each group. Polyamine levels were also assessed in each of these groups after 26 weeks of treatment with this carcinogen +/- MDL 72527. In addition, in view of recent studies that have indicated that polyamines may influence certain oncogenes in human colonic carcinoma cells, tumors from DMH +/- MDL 72527 were analyzed for K-ras mutations. The results of these experiments demonstrated for the first time that: (i) MDL 72527 was a specific inhibitor of polyamine oxidase in normal and malignant colonic tissue; (ii) concomitant administration of this agent with DMH enhanced the elevation of colonic N1-acetylspermidine and significantly reduced the mean colonic tumor burden, as assessed by total tumor area per rat, produced by this carcinogen alone; (iii) analysis of K-ras mutations revealed a similar incidence (62-69%) in adenocarcinomas for both groups (+/- MDL 72527); (iv) however, analysis of the K ras-mutated and non-mutated tumors revealed that in both carcinogen-treated groups (+/- MDL 72527), tumors with such mutations were smaller than their counterparts without such genetic alterations. Moreover, MDL 72527 reduced the average size of tumors, with and without such mutations, to a similar extent. PMID- 2265466 TI - Monomorphic and polymorphic isozymes of arylamine N-acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N-acetylation polymorphism. AB - Two forms of cytosolic acetyltransferases, AT-I and AT-II, have been purified from hamster livers, and a comparison made of their chemical and catalytic properties and genetically expressed difference. Homogeneous AT-I and AT-II were 31 and 30 kd respectively on SDS-PAGE and catalyzed efficiently various N- and O acetylations in their reconstitution systems. AT-I used both acetyl CoA and arylhydroxamic acids as acetyl donors, while AT-II did not utilize arylhydroxamic acids as acetyl donors. In the reconstitution system, purified AT-I, but not AT II, catalyzed acetyl CoA-dependent O-acetylation of 2-N-hydroxyamino-6 methyldipyrido[1,2-alpha:3', 2'-d]imidazole (N-OH-Glu-P-1) and arylhydroxamic acid-dependent N-acetylation of 4-aminoazobenzene (AAB). On the other hand purified AT-II showed high activities of acetyl CoA-dependent N-acetylation of 2 aminofluorene (AF) and p-aminobenzoic acid (PABA). Polyclonal antibodies raised against AT-I inhibited cytosolic acetylations of N-OH-Glu-P-1 and AAB, and to a lesser extent of AF, while PABA N-acetylation was only marginally inhibited. Using Western blots, both AT-I and AT-II were recognized by the antibodies. AT-I was detectable in all the livers examined, and the content did not differ among the individuals (monomorphic distribution). In contrast, AT-II was distributed polymorphically, and the trimodal distribution of AT-II (high, intermediate and low) was correlated with the phenotype identified by cytosolic N-acetylations of AF and PABA (rapid, intermediate and slow). In addition, cross-mating experiments with intra- and inter-phenotype animals confirmed that hepatic AT-II isozyme is inherited by a Mendelian co-dominant trait. These results indicate that the polymorphic appearance of an acetyltransferase, AT-II, is responsible for the N acetylation polymorphism in individual hamsters. PMID- 2265467 TI - A new sensitive fluorometric assay for the metabolism of (--)-7,8-dihydroxy-7,8 dihydrobenzo[a]pyrene by human hair follicles. AB - A new sensitive fluorometric assay was established to measure the stereospecific formation of benzo[alpha]pyrene tetrols formed after cytochrome P450-dependent metabolism of (--)-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene by human hair follicles. This simple assay requires three human hair follicles and a low (0.5 2.0 microM) substrate concentration and has a limit of detection of approximately 0.3 fmol of tetrols. Freshly isolated human hair follicles from 20 adult volunteers (10 non-smokers and 10 smokers) were assayed. While intersubject and seasonal variations were observed, the assay was found to be reproducible for a given subject. This rapid and non-invasive assay provides a new means for metabolic phenotyping of human subjects for their capacity to metabolize (--)-7,8 dihydroxy-7,8-dihydrobenzo[alpha]pyrene to its carcinogenic form (+)anti benzo[a]pyrene diolepoxide. PMID- 2265468 TI - Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue. AB - The level of expression of glutathione S-transferases (GSTs) and cytochrome P450s in breast tissue are potentially important determinants in both the susceptibility of this tissue to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. In this study we have investigated the expression of these proteins in 41 tumor and surrounding normal breast tissue samples by measurement of substrate metabolism. Western blot analysis and immunohistochemistry. In addition, we have quantitated the concentration of alpha, mu and pi class GST subunits using radioimmunoassay. All three classes of GST were expressed in breast tissue. The pi and mu class enzymes preponderate. Both the polymorphic mu class GST as well as a further form, present in all individuals, were found in high concentration. The polymorphic mu class GST was expressed in approximately 50% of the samples, which is consistent with the frequency of this polymorphism in the population and therefore does not appear to be a factor in susceptibility to this disease. Interestingly, although levels of the alpha class GST were very low, in two tumor samples extremely high levels of the B1B1 subunit were detected. Immunohistochemical studies showed significant variability in the localization of the pi class of GST between normal epithelial cells, infiltrating plasma cells and tumor cells, and in some samples GST pi appeared to be almost absent from the tumor tissue. No direct, or inverse correlation was found between GST pi concentration determined by radioimmunoassay and estrogen receptor levels. However, when studied by immunohistochemistry estrogen receptor negative tumors did tend to have higher GST pi content. The only cytochrome P450 detectable by Western blot analysis was a member of the P450IIC gene family. This was apparently distinct from the P450IIC proteins expressed in the liver and was detected in normal and tumor tissues to a similar extent. PMID- 2265469 TI - Potent genotoxicity of halogen lamps, compared to fluorescent light and sunlight. AB - The light emitted by halogen lamps induced mutations in Salmonella typhimurium and DNA damage in Escherichia coli, as shown by the hypersensitivity of DNA repair-deficient strains. The mutagenicity of halogen lamps was considerably higher than that of fluorescent light and of sunlight, even at much lower illuminance levels. Excision mechanisms and SOS functions were involved in repairing light-induced base-pair substitutions and frameshift errors in bacterial DNA. At variance with solar irradiation, which produces mutagenic effects over a wide UV spectrum, genotoxicity of halogen lamps was almost exclusively due to far-UV wavelengths transmissible through UV-R-250 and UV-R-280 interference filters. The main mutagenic component of fluorescent light (254 nm) were almost 10(4)-fold more mutagenic than near-UV wavelengths (365 nm). All light sources exhibited some residual mutagenicity even following filtration through various cloths. On the other hand, appropriate glass or plastic covers consistently prevented mutagenic effects. This emphasizes the urgent need for a compulsory shielding of halogen and fluorescent lamps in order to prevent unnecessary exposures to genotoxic and potentially carcinogenic UV radiations. PMID- 2265470 TI - Decreased expression of the glutathione S-transferases alpha and pi genes in human renal cell carcinoma. AB - Using the polymerase chain reaction (PCR), a human kidney glutathione S transferase (GST) alpha cDNA clone (GST alpha 12 K) was synthesized; it is identical to a known liver GST alpha cDNA clone except for one base change (G--- A), indicating that an alpha class gene expressed in human kidney is similar to one expressed in human liver. Comparisons were made in the expression of GST alpha and GST pi between renal cell carcinoma and adjacent non-neoplastic tissue. Messenger RNA expression in 30 cases was determined by Northern blotting, and GST protein from nine of these cases was analyzed by HPLC. The GST alpha gene products were expressed at near-zero levels. The GST pi gene product was the predominant GST in tumors, but was decreased in absolute amount compared with control tissue, the tumor/control ratios for the GST pi gene obtained by Northern blots and HPLC analysis being 0.50 +/- 0.07 and 0.36 +/- 0.07 respectively. The resulting pattern in renal cell carcinoma therefore shows a predominance of GST pi. Since it is assumed that renal cell carcinoma derives from the proximal tubular epithelial cells which are high in GST alpha, this implies a dedifferentation in the GST expression pattern. PMID- 2265471 TI - Nucleophilic selectivity of alkylating agents and their hypermutability in Drosophila as predictors of carcinogenic potency in rodents. AB - The nucleophilic selectivity (Swain-Scott s constant or initial 7-alkylguanine/O6 alkylguanine ratio in DNA) of 60 alkylating agents, mostly monofunctional or cross-linking was compared to their carcinogenic potency in rodents (median TD50 estimates) and to two genotoxicity indices in Drosophila: (i) hypermutability, measured by the increased frequency of induced sex-linked recessive lethal mutations (SLRL) in a strain defective in DNA excision repair (exr-), as compared to the wild-type (exr+); (ii) relative clastogenic efficiency, expressed by the ratio of chromosomal aberrations (ring-X loss) to SLRL determined in the exr+ strain. For a subset of direct-acting, monofunctional alkylating agents, nucleophilic selectivity and TD50 values or hypermutability indices were linearly correlated. In addition, the hypermutability indices in Drosophila by methylating or ethylating procarcinogens were similar to the corresponding values of their ultimate metabolites. In contrast, cross-linking agents, including antitumour drugs, did not show these positive correlations. The relative clastogenic efficiencies in Drosophila of 26 direct-acting, alkylating carcinogens increased with both their cross-linking activity and nucleophilic selectivity. By analyzing mutational spectra in Drosophila induced in the vermilion gene by four monofunctional alkylating agents with contrasting s values, critical DNA lesions, i.e. type of base pair substitution mutations, deletions, insertions, involved in genotoxicity were pinpointed. Thus, these multi-endpoint analyses should, as a new approach, assist in the quantitative risk evaluation of genotoxic agents. PMID- 2265473 TI - Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. AB - Cholecystokinin (CCK) has been shown to promote pancreatic growth and azaserine induced pancreatic carcinogenesis in rats. The present study was carried out to determine effects of CCK on pancreatic growth and carcinogenesis in the N nitrosobis(2-oxopropyl)amine (BOP) hamster model. One hundred male Syrian golden hamsters were injected s.c. once weekly with 20 mg BOP/kg body wt at 6, 7 and 8 weeks of age, and divided into four groups of 25 animals each, which received one of the following treatments (once daily, 3 days/week for 16 weeks): gelatin; CR 1409, a potent CCK-receptor antagonist; CCK-8, 2.5 micrograms/kg body wt; or CCK 8 in combination with CR-1409 (30 min before CCK treatment). The animals were killed after 19 weeks. The growth of the pancreas but not the incidence of pancreatic (pre)neoplastic lesions was enhanced by CCK-8. CR-1409 did not influence the effect of CCK on pancreatic growth. PMID- 2265472 TI - Dose-dependent inhibition of large intestinal cancer by inositol hexaphosphate in F344 rats. AB - We have previously reported that inositol hexaphosphate (InsP6) inhibits mitosis and large intestinal cancer (LIC) in F344 rats and CD1 mice when given as 1 or 2% solution in drinking water at the unadjusted pH of 11.3. The purpose of this study was to determine whether InsP6 (i) shows a dose-response inhibition of LIC, and (ii) retains its anti-neoplastic effect at physiological pH. Since InsP6 is known to be a chelator of divalent cations, in preparation for putative clinical trials in humans, we also looked at the mineral bioavailability. F344 rats were fed 0.1% (pH 10.8), 1% (pH 11.3) and 1% (pH 7.4) Na-InsP6 in drinking water. Two weeks following the beginning of InsP6 supplementation, rats were given six injections of azoxymethane (AOM) at a dose of 8 mg/kg body wt/week and were killed 30 weeks following the last injection. Compared to the untreated control rats injected with AOM, 1% InsP6 (pH 11.3) reduces tumor prevalence by 52.2% (P less than 0.01), tumor frequency by 55.8% (P = 0.001) and tumor size by 62.3% (P = 0.001); 0.1% InsP6 showed a lesser reduction in tumor prevalence (21%) but a greater reduction in tumor size 71% (P = 0.001). While there was no significant difference in tumor prevalence and frequency between the two pH groups, the tumor size following 1% InsP6 (pH 7.4) was the smallest (65% smaller than those of pH 11.3, P less than 0.005). There was no significant difference in the serum Mg2+, Ca2+, Fe2+ and Zn2+ level between control rats and those treated with 1% InsP6. We therefore demonstrate that InsP6 (i) is consistently anti-neoplastic for LIC in a dose-dependent manner, (ii) retains its anti-neoplastic activity at physiological pH and (iii) has no demonstrable toxic effect on long-term administration as evident by body wt data and serum mineral levels. PMID- 2265474 TI - H-ras activation and ras p21 expression in bladder tumors induced in F344/NCr rats by N-butyl-N-(4-hydroxybutyl)nitrosamine. AB - Bladder tumors were induced in male F344/NCr rats by administration of N-butyl-N (4-hydroxybutyl)nitrosamine (BBN) at 500 p.p.m. in their drinking water for 12 weeks. Twenty-one bladder tumors that developed between 25 and 50 weeks after BBN administration was begun were evaluated for immunoreactivity with polyclonal or monoclonal antibodies raised against ras p21, for amplification of ras genes by Southern blotting, and for activating point mutations in ras genes by selective oligonucleotide hybridization of products from polymerase chain reaction (PCR). Increased expression of ras p21 was detected by avidin-biotin immunohistochemistry in 18/21 (85%) of the neoplastic bladder lesions. By Southern analysis, there was no significant amplification of H-ras, K-ras or N ras in any of the tumors except one that showed a 5-fold amplification of K-ras. Point mutations in ras genes were detected by selective oligonucleotide hybridization of the products of PCR. Of the 21 bladder tumors, three tumors were shown to have mutations in codon 12 (GGA----GAA), six tumors in codon 61 (two CAA ---CTA, four CAA----CGA), and one in both codon 12 (GGA----GAA) and codon 61 (CAA ---CGA), all in H-ras. Thus 10 of 21 tumors has ras gene mutations in a portion of the tumor cells. The variable pattern of point mutation in H-ras suggests that these mutations may not all be a direct consequence of interaction of BBN metabolites with H-ras. Enhanced expression of ras p21 was always focal and was not necessarily associated with transforming ras mutations. It is therefore suggested that tumorigenesis in BBN-initiated bladder cells might involve H-ras activation as part of a multistep pathway; however, H-ras involvement is not obligatory for tumor development. PMID- 2265475 TI - Roles of cytochrome P450IIE1 in the dealkylation and denitrosation of N nitrosodimethylamine and N-nitrosodiethylamine in rat liver microsomes. AB - N-Nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) are widely occurring nitrosamines and require enzyme-catalyzed activation for their carcinogenic actions. The low Km forms of the enzyme are generally considered to be important in the activation of environmental carcinogens. In this work we examined the role of cytochrome P450IIE1--a constitutive enzyme that is also inducible by acetone, ethanol, fasting and other factors--in catalyzing the dealkylation and denitrosation of these two carcinogens. The experimentally determined Km value of NDMA demethylase depended upon the experimental conditions and was lower when lower protein concentrations were used. Low Km values of 15-20 microM were observed for NDMA demethylase with different preparations of microsomes. In the deethylation of NDEA, a low Km of approximately 40 microM was observed for both control and acetone-induced microsomes. Immunoinhibition studies indicated that P450IIE1 was responsible for almost all the low Km NDMA demethylase activity in acetone-induced microsomes and greater than 80% in control microsomes. This enzyme was also responsible for about three-quarters of the low Km NDEA deethylase activity in acetone-induced microsomes and about half in control microsomes. The denitrosation of NDMA and NDEA was inhibited to approximately the same extents as the dealkylation reactions under different experimental conditions, suggesting the involvement of the same enzyme and perhaps a common initial intermediate in these two types of reactions. The relevance of this work and its relationship to related information in the literature are discussed. PMID- 2265476 TI - Measurement of chemically induced cell proliferation in rodent liver and kidney: a comparison of 5-bromo-2'-deoxyuridine and [3H]thymidine administered by injection or osmotic pump. AB - Different labeling methods for quantitating cell proliferation were evaluated in livers and kidneys of control and chemically treated mice and rats. The percentage of cells in S-phase (labeling indices) were compared in tissues of animals given either 5-bromo-2'-deoxyuridine (BRDU) or [3H]thymidine. These DNA precursor labels were delivered either by a single i.p. injection 2 h prior to killing the animals or via the s.c. implanted osmotic pump for 3 or 6 days. B6C3F1 mice and male F344 rats were exposed to either a peroxisome proliferator and hepatocarcinogen, Wy-14,643 (WY), in the diet at 0.1% for up to 5 days, or a non-genotoxic mouse liver and male rat kidney carcinogen, 1,4-dichlorobenzene (DCB), in corn oil by gavage for up to 5 days in mice (600 mg/kg/day) or up to 3 weeks in rats (300 mg/kg/day, 5 days per week). Labeling indices (LIs) in the liver and kidney were similar in BRDU- and [3H]thymidine-labeled mice and rats. Cell proliferation was increased in livers of both species of WY- and DCB-treated animals when compared to controls. After 4 days of chemical treatment with continuous administration of a DNA precursor label during the last 3 days of treatment, LIs in controls, DCB- and WY-treated mouse livers were 0.7, 19 and 17% for BRDU and 0.9, 15 and 13% for [3H]-thymidine respectively. Furthermore, BRDU and [3H]-thymidine labeled the same population of cells as revealed by similar patterns of cell labeling in the livers and kidneys of treated animals. The LI for BRDU- and [3H]thymidine-labeled renal proximal tubular cells was 7.7 and 8.0% respectively, in rats receiving DCB for 4 days and DNA precursor label during the last 3 days of treatment, while the LI for controls was 4.3 and 3.7% respectively. The renal proximal tubular cell LI increased to 11% in BRDU-labeled rats treated with DCB for 3 weeks. LIs in both liver and kidney were greatest in control and treated animals that received the DNA precursor label via osmotic pumps for 6 days, and least in 2 h pulse-labeled animals. However, induction of hepatic LI in treated over control animals was greatest for treated animals labeled for 3 days. These results demonstrate comparable cell labeling of cells in S-phase with either BRDU and [3H]thymidine labeling methods. BRDU presents no radioactive containment problems, and results are obtained more rapidly than [3H]thymidine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2265477 TI - Proposed structures for an amino-dimethylimidazofuropyridine mutagen in cooked meats. AB - New analytical data allow the structure of a potent mutagen previously reported present in cooked meats to be proposed. The mutagen was isolated from a fried mixture of beef, creatine and milk, simulating a meat recipe previously shown to produce this compound. High-resolution mass spectra indicate a mol. wt of 202 and the formula C10H10N4O. Mutagenic activity was 10,000 TA1538 revertants per microgram in the Ames Salmonella test. From the NMR data, peaks showing an amino group at 6.812 p.p.m. and an N-methyl group at 3.520 p.p.m. were found, typical for the amino-imidazo structure commonly found in cooked meats. Additional signals at 2.440 p.p.m. (three protons), 7.653 (one proton) and 6.531 (one proton) were observed. A structure of 2-amino-(1 or 3),6-dimethylfuro[2,3(or 3,2) e]imidazo- [4,5-b]pyridine was proposed based on the mass and NMR spectral data and comparison to literature compounds. The methylimidazofuropyridine reported here is probably related to another mutagen in cooked meats with a mol. wt of 216 with an additional methyl group on either the furan or pyridine rings. PMID- 2265478 TI - Aflatoxin-albumin adducts in human sera from different regions of the world. AB - An immunoassay now permits the determination of human exposure to aflatoxin at an individual level and consequently allows a better assessment of the role of aflatoxin, and its interaction with hepatitis B virus infection, in the aetiology of liver cancer. Measurements of aflatoxin bound to serum albumin in children and adults from various African countries show that between 12 and 100% contain aflatoxin-albumin adducts, with levels up to 350 pg AFB1-lysine equivalent/mg albumin. In Thailand, lower levels and prevalence of this adduct were observed, while no positive sera were detected from France or Poland. Data are presented showing that exposure to this carcinogen can occur throughout life and the relevance of these observations to the understanding of the multifactorial aetiology of liver cancer in these countries is discussed. PMID- 2265480 TI - Benign breast disease. An update. PMID- 2265479 TI - In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human liver microsomes by naringenin and other flavonoids. AB - Recent in vivo studies in humans have shown a dramatic effect of grapefruit juice in blocking the oxidation of dihydropyridine calcium channel blockers. The flavonoid naringin is the most abundant natural product specific for grapefruit and related citrus--the aglycone naringenin, known to be readily formed from naringin in humans, was found to inhibit the oxidation of the dihydropyridines nifedipine and felodipine in human liver microsomal preparations. These observations were of interest in light of the knowledge that the same human liver cytochrome P450 (IIIA4) appears to be a major catalyst in both nifedipine oxidation and aflatoxin B1 activation. Several flavones inhibited the in vitro activation of aflatoxin B1 in a system employing umuC gene activation due to DNA damage in Salmonella typhimurium TA1535/pSK1002, with naringenin being as effective as any. The high concentration of derivatives of naringenin in certain citrus fruits may be of relevance to cancer chemoprevention involving those carcinogens that are activated by cytochrome P-450IIIA4. PMID- 2265482 TI - Dose-dependent increase in plasma interleukin-6 after recombinant tumour necrosis factor infusion in humans. AB - Several studies have shown that the cytokine interleukin-6 (IL-6) is produced in response to tumour necrosis factor (TNF) in vitro. This study examines the in vivo relation between these two cytokines with assays of plasma IL-6 and TNF levels in subjects with chronic hepatitis B undergoing immunomodulatory therapy with recombinant TNF (rTNF). Plasma IL-6 was detected from 20 min after rTNF infusion with levels peaking after 2-3 h and levels correlated with the dose of rTNF administered (r = 0.67, P = 0.004). Peak levels of IL-6 (mean 295, range 266 297 ng/l) were lower than those seen in certain disease states despite the very high peak levels of rTNF (mean 11,750, range 5623-18,620 ng/l). These findings suggest that the very high levels of IL-6 found in certain disease states are not purely the result of circulating TNF. Other factors such as endotoxin or other cytokines may also play a role in determining levels of plasma IL-6. PMID- 2265481 TI - Can persistent IgE responses be suppressed? PMID- 2265483 TI - Isotype-selective abrogation of established IgE responses. AB - Chemically modified allergens have been extensively studied in an attempt to develop materials of increased efficacy and improved safety for use in the immunotherapy of allergic disease. Most of the strategies that have been developed yield products that strongly inhibit de novo IgE responses but have only marginal impact on ongoing IgE responses. We report the virtual abrogation of pre-established murine anti-ovalbumin IgE responses using a glutaraldehyde polymerized ovalbumin preparation (OA-POL) of Mr 3.5 x 10(7). Secondary IgE responses are inhibited by 97-99% over a period of at least 8 months following three i.p. courses of OA-POL treatment. Administration of five additional ovalbumin [Al(OH)3] booster immunizations over this period fails to alter this unresponsive state. The inhibition of antigen-specific IgE responses is isotype specific. PMID- 2265484 TI - An experimental influenza subunit vaccine (iscom): induction of protective immunity to challenge infection in mice after intranasal or subcutaneous administration. AB - An experimental influenza virus (A/PR/8/34(H1N1] vaccine was tested and evaluated in mice. The mice were inoculated once or twice intranasally or subcutaneously with 1 or 10 micrograms of iscoms prior to challenge with high dose of live virus. It was demonstrated that two intranasal administrations were as efficient as two s.c. administrations, both routes inducing high levels of antibody and protection against challenge infection. With a one-dose regimen, the s.c. route induced a somewhat higher antibody response than the intranasal route; this might be explained by technical difficulties connected with an intranasal administration. PMID- 2265485 TI - Extracorporeal immunoadsorption therapy on rats. In vivo depletion of specific antibodies. AB - A technique for extracorporeal immunoadsorption of circulating specific antibodies from the plasma of rats is described. Catheterization of rats was performed using the carotid and the jugular blood vessels. The rats were treated non-anaesthetized. Blood was pumped continuously through a hollow-fibre plasma filter at a rate of 1.5 ml/min and plasma was separated and passed through an adsorbent column at a flow of 0.2 ml/min. The treated plasma was mixed with the blood cells before being returned to the rat. The column contained the antigen covalently linked to agarose beads. About three plasma volumes were treated during a period of 3 h and 30 min, which resulted in an antibody depletion of about 90-95%. The antibody levels returned to pre-adsorption levels after 4-5 days, or in some cases even exceeded the titres before treatment. PMID- 2265486 TI - Flow cytometric and functional analysis of mononuclear cells infiltrating the liver in experimental autoimmune hepatitis. AB - Experimental autoimmune hepatitis was produced by immunizing Wistar rats with syngeneic liver proteins. Mononuclear cells infiltrating the liver tissue were identified by immunohistochemical techniques using monoclonal antibodies specific for subpopulations of rat lymphocytes. The strong infiltration of CD8+ cytotoxic T lymphocytes (CTL) were found in the portal areas. Subpopulations of mononuclear cells infiltrating the liver, spleen cells and peripheral blood lymphocytes were identified by flow cytometry. Flow cytometric analysis revealed the presence of CD5- and CD8+ lymphocytes in the liver tissues. Mononuclear cells infiltrating the liver were isolated from Wistar rats having autoimmune hepatitis to determine whether those exhibit cytotoxicity against syngeneic hepatocytes; they exhibited cytotoxicity against isolated syngeneic hepatocytes, but failed to lyse K562 cells, syngeneic concanavalin A-activated splenocytes and allogeneic hepatocytes. Depletion of CD8+ T cells significantly reduced the cytotoxic ability of mononuclear cells infiltrating into the liver against syngeneic hepatocytes. These findings support the idea that liver cell injury in experimental autoimmune hepatitis may at least in part be mediated by CTL. PMID- 2265487 TI - Antibodies to the peptide from the plasmid-coded Yersinia outer membrane protein (YOP1) in patients with ankylosing spondylitis. AB - Seventy-five Norwegian patients with ankylosing spondylitis (AS) were studied for class-specific antibody response against synthetic peptide, P81, representing the sequence of plasmid-coded outer membrane protein of Yersinia (YOP1) containing four amino acid homology (TDRE) with HLA-B27 sequence. Ten (16.7%), five (8.3%) and seven (11.2%) of 60 male AS patients showed elevated anti-YOP1 P81 antibody of IgA, IgG, and IgM class, respectively, whereas for each isotype only one (4%) of 25 healthy male controls was positive. Differences were not observed between female patients and controls. In all isotypes, antibody-positive patients were more frequently found in patients with active disease. The anti-YOP1 P81 antibody levels of the patients were generally not correlated with the antibody levels against the peptide representing the hypervariable region of HLA-B27 (B27 peptide). However, in one patient the antibody was shown to react with both peptides by cross-inhibition analysis. Overall, it appears that any causal relationship between YOP1 and pathogenesis of AS is not strong. Immunogenicity and cross-reactivity of the YOP1 region encompassing the TDRE sequence particularly at the T cell level require further study. PMID- 2265488 TI - Anti-DNA idiotype- and anti-idiotype-specific T cell responses in patients with systemic lupus erythematosus and their first-degree relatives. AB - We examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE), their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a murine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE. PMID- 2265489 TI - Lipopolysaccharide from gram-negative bacteria enhances polyclonal B cell activation and exacerbates nephritis in MRL/lpr mice. AB - Depletion of B cells in mice bearing the lymphoproliferation (lpr) gene reduces lymphoproliferation and polyclonal B cell activation (PBA) and attenuates mononuclear cell vasculitis. We sought to verify whether the obverse was true, i.e. whether enhancement of B cell activity might exacerbate the nephritis of MRL/lpr (MRL) mice, a lupus-prone strain. The experimental approach was designed to address three questions: whether naturally occurring PBA in MRL mice could be further enhanced; whether enhanced PBA would exacerbate nephritis; and whether the mechanism of nephritis exacerbation involved interference with mononuclear phagocyte system (MPS) function. To enhance B cell activity, we injected MRL mice with lipopolysaccharide (LPS) from Gram-negative bacteria, a potent B cell activator. To determine whether nephritis was exacerbated, we performed immunopathologic studies and tests of renal function. To verify whether nephritis exacerbation involved impairment of MPS function, we probed the kinetics of immune complex removal from the circulation, their uptake by the liver and spleen, and their localization in kidney tissue. The results indicate that in MRL mice: (i) spontaneous PBA can be enhanced by LPS; (ii) enhancement of PBA by LPS exacerbates nephritis; and (iii) the MPS is already saturated, presumably due to excessive production of endogenous immune complexes. Thus, further increase in immune complex formation due to enhanced PBA by LPS results in increased localization of immune complexes in kidneys and exacerbated nephritis. PMID- 2265490 TI - Temporary breakdown of immunological tolerance to dsDNA and nucleohistone antigens in rabbits infected with rinderpest virus. AB - The rabbit-passaged L strain of rinderpest virus (RV) causes the transient induction of anti-nuclear antibodies (ANA) in rabbits. It has been shown by an indirect immunofluorescence test that the target antigens of these ANA are DNA and/or DNA-histone complexes (nucleohistone). Here detailed examinations of the target antigens were carried out by ELISA, and it was revealed that rabbit sera contained three types of antibodies: antibodies reacting equally with both dsDNA and ssDNA; those reacting with ssDNA alone; and those reacting with nucleohistone. Epitopes recognized by the third type consisted of complexes of dsDNA and H2A + H2B or of dsDNA and H2B. All types of antibodies were antigen specific. Since the diversity of ANA among experimental rabbits was large, it was suggested that genetic background is important in the induction of anti-dsDNA antibodies in this system. Moreover, early induction of antibodies to nucleohistone and the rapid disappearance of ANA suggest that B cell proliferation/maturation for continuous production of ANA requires factors other than RV infection. This system may help elucidate the mechanisms of ANA induction and the development of autoimmune diseases. PMID- 2265491 TI - Immunologic abnormality in NZB/W F1 mice. Thymus-independent expansion of B cells responding to interleukin-6. AB - We have previously reported that B cell abnormality in NZB/W F1 mice developed independently of thymus. Here we examined further whether B cells from NZB/W F1 mice respond to interleukin-6 (IL-6), a factor for terminal differentiation of B cells. When freshly isolated splenic B cells were incubated for 5 days in the presence of human IL-6, an increased production of both IgM and IgG, including anti-DNA antibody, was evident in NZB/W F1 mice; there was no increase in BALB/c mice. A magnitude of augmentation in IgG but not IgM production by IL-6 became more apparent in older NZB/W F1 mice. The increased immunoglobulin production seen with IL-6 was neutralized by treatment with rabbit anti-recombinant human IL 6 antibody. As B cells from athymic NZB/W F1 nude mice also responded to IL-6, it was suggested that B cells in NZB/W F1 mice differentiated into the IL-6 responding state in a thymus-independent manner. This B cell abnormality may be associated with the pathogenesis of autoimmune disease in NZB/W F1 mice. PMID- 2265492 TI - A delayed-type hypersensitivity skin-test system using the insulinoma cell line RINm5F to monitor beta cell-specific cellular autoimmune reactivity in the spontaneously diabetic BB/O rat. AB - Islet-specific autoimmune reactivity (humoral and cell-mediated) is the basis for the insulitis process of type I diabetes mellitus. In this report a delayed-type hypersensitivity (DTH) skin test was used to monitor the presence of an islet specific cell-mediated autoimmune component in BB/O rats. The BB/O rat is a strain characterized by the spontaneous development of type I diabetes. Intact RINm5F cells as well as a RINm5F cell membrane preparation were used as DTH skin test antigens. Rats of different ages and disease stages were tested in the ear with the insulinoma cell line and its cell membrane preparation. As control antigens, the fibroblast cell line 3Y1 and a cell membrane preparation made thereof were used. The DTH reaction system showed a positive cell-mediated reactivity in BB/O rats for membrane-bound RINm5F cell antigens, and not for the control fibroblast 3Y1 cell membrane determinants. The true DTH character of the skin test was established by the time-course of the reaction (maximum at 24 h), the histopathology (infiltration by dendritic cells, lymphocytes and macrophages), and the possibility to transfer the reaction with spleen cells and lymph node cells. The DTH test towards RINm5F cells showed the highest prevalence of positivity (100%) in BB/O rats around the onset of diabetes (3 weeks before to 3 weeks after the onset of glucosuria). The prevalence of DTH positivity was 56% in the period of more than 3 weeks before the onset of glucosuria. In BB/O rats with a duration of glucosuria of more than 3 weeks, the prevalence of positivity was around 60-70%. PMID- 2265493 TI - Serological monitoring of previously treated lepromatous patients during a course of multiple immunotherapy treatments with heat-killed Mycobacterium leprae and BCG. AB - Two-hundred and seventy lepromatous patients who had completed treatment received multiple treatments with heat-killed M. leprae and BCG and were monitored for changes in humoral responses to M. leprae-specific antigens. These patients were divided into four treatment groups: placebo (n = 69); BCG (n = 68); M. leprae only (n = 71); and BCG + M. leprae (n = 62). They were monitored for 15 months, receiving five inoculations for each treatment regimen. Two ELISA systems, one measuring antibodies to M. leprae-specific epitopes of the phenolic glycolipid I (NDO-ELISA) and the other of 36-kD protein antigens (INH-ELISA) were used to measure serological changes during this period of immunotherapy. We found no significant increase in serological reactivity with the different treatments, as measured by NDO-ELISA. INH-ELISA similarly showed no significant changes, with the exception of increased values in a small group 13% (36/270) which became skin test-positive during the course of the study. The NDO-ELISA results indicate that use of heat-killed M. leprae or BCG + heat-killed M. leprae did not stimulate the humoral response to the semi-synthetic PG-I antigens of M. leprae. Thus, the NDO ELISA may be useful in monitoring the outcome of vaccine trials in which killed M. leprae or M. leprae fractions are used, since seroconversion may indicate disease, rather than a response to the vaccine material. PMID- 2265494 TI - IgG subclasses in human chronic schistosomiasis: over-production of schistosome specific and non-specific IgG4. AB - IgG subclasses were determined quantitatively in sera from 63 Egyptian men who were infected with Schistosoma mansoni. Total and antigen-specific IgG was measured pre- and post-treatment. Total IgG subclass antibodies were determined by immunoradiometric assay (IRMA) using monoclonal antibodies (MoAbs). The anti worm and anti-egg specific S. mansoni IgG subclass antibodies were quantitatively measured by ELISA using specific MoAbs and standards obtained by affinity chromatography. Our data show that total IgG of the patients was elevated in the range of two to three times above normal. The magnitude of increase differed markedly among the four subclasses of IgG. The IgG1, IgG2 and IgG3 concentrations were approximately two to four times higher than normal, whereas the IgG4 concentrations was 20 times normal (9000 mg/l). IgG1 and IgG4 tended to dominate the IgG subclass distribution of anti-soluble worm antigen preparation (SWAP) antibodies followed by IgG2 and IgG3. On the other hand, IgG1 and IgG2 dominated the IgG subclass distribution of anti-soluble egg antigen (SEA) antibodies. As with IgG1, IgG2 and IgG3, most IgG4 was non-specific. The role of IgG subclasses in the pathogenesis of schistosomiasis is not clear. However, the high concentration of IgG4 might act as IgE blocking antibody, possibly as anti idiotypes that may play a role in down-regulation of the immune system when it is challenged with an excess of antigen. PMID- 2265495 TI - Changes in the serum concentration and the glycosylation of human alpha 1-acid glycoprotein and alpha 1-protease inhibitor in severely burned persons: relation to interleukin-6 levels. AB - The relation between interleukin-6 (IL-6) levels and changes in serum concentrations and glycosylation (concanavalin A affinity) of two human acute phase glycoproteins, alpha 1-acid glycoprotein (AGP) and alpha 1-protease inhibitor (PI), was studied in sequential serum samples of burn patients. The level of IL-6 was already increased at the first day following injury, and after a dip at day 2 or 3 rapidly reached a second maximal value at day 4 or 5. The serum concentrations of AGP and PI reached their maximal values after day 5 and remained at a high level throughout the total period studied (7 weeks). The concanavalin A reactivities of both acute-phase glycoproteins were found to be elevated only during the first 2-2.5 weeks. Maximal values were observed on day 2 and from day 7 to 16, following closely the rise and fall of the IL-6 serum level. After day 16, the concanavalin A affinity rapidly declined long before a decrease was observed in the serum concentrations of AGP and PI. Our previous in vitro studies have indicated an involvement of IL-6 in the induction of both secretion and increased concanavalin A affinity. This study indicates that IL-6 could play a causal role in the induction of both phenomena in vivo. PMID- 2265496 TI - Preparation of anti-T idiotype monoclonal antibody reacting with human T leukaemic cell lines and with a small percentage of peripheral T lymphocytes. AB - Monoclonal antibody (MoAb) KT38 raised against a human T leukaemic cell line TALL 1, reacted with another T leukaemic cell line Jurkat, but not with any other cell lines tested. The co-modulation of CD3 and KT38 antigen was observed with stimulations of either MoAb T3 or KT38 on both TALL-1 and Jurkat. Upon radioimmunoprecipitation and SDS-PAGE analysis, MoAb KT38 precipitated the heterodimer of 40-60 kD from Jurkat and TALL-1 under reducing conditions. Thus, MoAb KT38 is considered to be an anti-T idiotype (Ti) antibody to TALL-1 and Jurkat cells. MoAb KT38 was also shown to react with a minor population of peripheral blood lymphocytes (PBL) and with very few cells (0.5-2.0%) in the paracortical area of the lymph node. When PBL were stimulated in a KT38-coated culture flask for 5 days, the percentage of KT38-positive PBL was markedly increased. The CD3 antigen on these cultured PBL in the flask was modulated by the stimulation with MoAb KT38. Thus, it is suggested that a common idiotope exists on the T cell receptor of Jurkat, TALL-1 and a small percentage (1.9-6.1%) of PBL. PMID- 2265497 TI - [Chronic human colchicine myopathy]. AB - We report a case of myopathy induced by daily administration of colchicine. A 65 year-old man with gout and renal dysfunction had taken 1 mg of colchicine daily for 3 years. The dose was raised to 2 mg per day and two months later, he developed progressive weakness of the proximal limbs and had difficulty in rising from squatting and climbing stairs. Five months after the development of weakness, neurological examination showed proximal muscle weakness without wasting, generalized hyporeflexia and mild sensory loss and dysesthesia of the toes. Serum creatine kinase level was elevated to 788 IU/L and creatinine level was 2.1 mg/dl. Electromyography demonstrated myogenic changes with spontaneous activity. HE preparations of biceps muscle biopsy showed mild increase of variation in fiber size, small vacuoles with and without basophilic rims in some fibers and a few fibers with unevenly stained sarcoplasm. NADH-TR preparations showed numerous moth-eaten and targetoid fibers. The small rimmed vacuoles stained positively for acid phosphatase. Electron microscopy showed accumulation of lysosomes and autophagic vacuoles, and architectural changes and disruptions of myofibrils. After the discontinuation of colchicine, his strength and serum CK level normalized within two masquerading as polymyositis, may occur when customary doses of colchicine are given daily to patients with renal dysfunction. PMID- 2265498 TI - [An autopsy case of Neuro-Behcet's disease with the right middle cerebral artery occlusion on cerebral angiogram]. AB - A case of Neuro-Behcet's disease with the right cerebral artery occlusion on cerebral angiogram was reported. A 63 years old man complained of headache and slight fever without exacerbations of ocular and mucocutaneous lesions, 16 years after he had suffered from recurrent oral aphthous ulcers, genital ulcers, uveitis and erythema nodosum. Laboratory examination demonstrated pleocytosis in the cerebrospinal fluid, a low density area with contrast enhancement in right temporal and parietal lobes in brain CT, a high signal intensity in the same area in T2-weighted image in brain MRI and the occlusion of the right middle cerebral artery on cerebral angiogram. After admission, left homonymous hemianopsia and hemiparesis appeared. With steroid therapy, these symptoms diminished and abnormal findings in brain CT and MRI disappeared, but psychiatric symptoms were exacerbated gradually. Finally he died of agranulocytosis and pneumonia. Neuropathologic findings showed panarteritis of branches of the right middle cerebral artery and infarction of its territories in addition to perivascular infiltrations and foci of demyelination which were prominent in the cerebral basal regions. PMID- 2265499 TI - [Two siblings of distal hereditary motor neuropathy with choroideremia]. AB - Two brothers, 31 and 25 years of age, with distal hereditary motor neuropathy (distal HMN) and choroideremia are reported. Their parents were second cousins. During the first decade, their visual acuity gradually diminished with night blindness, accompanied by weakness of the legs. From the third decade, they noticed weakness of the hands. The neurological signs of both cases could be summarized as follows: bilateral pes cavus, Charcot-Marie-Tooth type distal atrophy and weakness of the four limbs, no sensory deficit, hyperreflexia in the upper limbs and knees, absent ankle jerks and plantar reflexes, and severe visual impairment due to choroideremia. In addition to these signs, the younger patient showed nystagmus and limb kinetic ataxia suggesting cerebellar involvement. Muscle biopsies and EMG studies revealed chronic neurogenic changes. MCV's in the median nerves were normal, but the extensor digitorum brevis muscles were totally denervated. SCV's, the amplitude of sensory action potentials and sural nerve biopsies were normal. In both patients, elevated CSF protein without pleocytosis and high level of serum IgA & E were demonstrated. Associations of choroideremia and abnormal laboratory findings as noted in our cases have not been so far reported in distal HMN, but we suppose these disorders may be genetically related. PMID- 2265500 TI - [A case of chronic inflammatory demyelinating polyradiculoneuropathy with nocturnal myoclonus]. AB - A 43-year-old man began to notice progressive tingling sensation in his legs and unsteadiness in walking in 1983. His symptoms diminished with prednisolone treatment. In 1986, the same symptoms developed again and abated with prednisolone and plasmapheresis. In 1988 he was admitted because of progression of the symptoms in the legs. Neurological examinations showed mild muscle atrophy and weakness in the legs, loss of the deep reflexes, and impairment of cutaneous and deep sensation of the extremities. Heel-knee test was unsteady, and his gait was wide-based. In addition, Babinski and Chaddock signs were positive bilaterally. He had spontaneous myoclonic jerks of his legs, so-called "tonic triple flexion". These jerks were particularly evident during sleep, and were considered to be "nocturnal myoclonus". The same jerks were provoked by painful stimuli or Babinski's, Marie-Foix's maneuver. These jerks were considered to be so-called "spinal automatism" of spinal or brainstem origin. The latencies of VEP on both sides were prolonged and ABR showed abnormalities indicative of brainstem lesion. There were no abnormalities in cranial and spinal MRI. Our case was proven to have central nervus system lesions in addition to findings of chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 2265501 TI - [Autonomic nervous functions in Alzheimer type and multi-infarct dementia--a hemodynamic study]. AB - As it has been recently postulated that patients with dementia have some altered neural transmission, these patients are speculated to accompany autonomic dysfunctions. The present study was aimed at investigating autonomic nervous functions in dementia of Alzheimer type (DAT) and multi-infarct dementia (MID). Hemodynamic autonomic functional tests were carried out on 14 patients with DAT (66.9 +/- 11.4 YO; mean +/- SD) and 9 patients with MID (73.1 +/- 7.5) and 16 age matched healthy volunteers as controls. Blood pressure, pulse rate and respiration were continuously measured. The degree of reflex bradycardia in Aschner's test, a parameter for parasympathetic functions, was significantly lower in MID than in DAT and in the healthy volunteers (p less than 0.01, p less than 0.05, respectively), but there was no significant difference between DAT and the healthy volunteers in this reaction. The degree of reflex hypertension in cold pressor test, a parameter for sympathetic functions, was not significantly different among 3 groups. The degree of orthostatic hypotension also failed to show any significant difference among the groups. From the above data, it is suggested that the patients with DAT have preserved autonomic nervous functions, but that the patients with MID have impaired parasympathetic and normal sympathetic nervous functions. PMID- 2265502 TI - [Chronic inflammatory demyelinating polyradiculoneuropathy associated with central nervous system involvement--as compared to multiple sclerosis]. AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with central nervous system (CNS) demyelinating lesions has recently been reported to mimic multiple sclerosis (MS). In this paper, a series of patients with CIDP were examined to see if they had CNS involvement. CIDP patients with CNS lesions were then compared to patients with MS with peripheral nervous system (PNS) involvement for similarities. CNS and PNS involvement were detected by clinical symptoms, neurological findings, neuro-otological and neuro-ophthalmological tests, electrophysiological examinations such as electroencephalography, evoked potentials, blink reflex, conventional peripheral nerve conduction studies and electromyography, as well as computed tomography and magnetic resonance imaging (MRI). There were 7 of 17 CIDP patients with CNS involvement, but only 2 of 59 MS patients with PNS lesions were found. The rate of CIDP with CNS involvement (41.2%) was higher than that of MS with PNS lesions (3.4%). The CNS signs and symptoms of 7 CIDP patients were not so constant as their PNS symptoms, and consisted of 1 case with optic neuritis, 4 cases with cerebellar atxia and/or nystagmus, and 3 cases with spinal symptoms. These signs and symptoms are all well known in MS. Prolonged latencies on evoked potentials and high signal white matter lesions on T2 weighted MRI, indicating demyelinating CNS lesions were also similar to those found in MS. The CNS involvement in those patients with CIDP was therefore similar in character to those found in MS, but was far less severe than the PNS finding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265503 TI - [Manometric study of the pharynx and pharyngoesophageal sphincter in myasthenia gravis]. AB - The purposes of this paper are to evaluate degree of dysphagia at the pharyngeal stage of swallowing in patients with myasthenia gravis (Osserman IIB). A catheter with three diode transducers 5 cm apart was swallowed through the nose into the upper esophagus. Firstly a patient was commanded to drink water of 1 ml at about five second intervals, and the swallowing pressures were recorded on condition that the speed of paper recording and catheter pull-through is the same 1 mm/sec. Secondly the swallowing pressures were recorded on condition that the middle transducer is fixed at the level of the upper esophageal sphincter and the speed of paper recording is 5 mm/sec before and after intravenous injection of 10 mg edrophonium chloride. Thirdly the resting pressure of upper esophageal sphincter was recorded on the same condition of the first recording. The results were as follows: (1) All seven patients showed extremely low swallowing pressure at the all level of the pharynx compared with healthy men. (2) At the edrophonium test all seven patients revealed increased percentage of swallowing pressure. (3) One patient showed poor relaxation of the upper esophageal sphincter. (4) The resting pressure of the upper esophageal sphincter was low compared with control. In myasthenia gravis manometric study of the pharynx and the pharyngoesophageal sphincter is a useful method for evaluating swallowing function. PMID- 2265504 TI - [Cardiomyopathy in Becker muscular dystrophy]. AB - In 6 patients with dystrophin-verified Becker muscular dystrophy (BMD), 3 patients had dilated cardiomyopathy (DCM group). The other 3 patients (non-DCM group) also had ECG abnormalities including incomplete right bundle branch block, left ventricular enlargement and intraventricular conduction defect. Between DCM and non-DCM group, there was no prominent difference in ages at onset, mean duration and severity of muscular weakness. Serum CK levels, and molecular weight and amount of dystrophin also showed no significant difference between two groups. On reviewing 14 BMD patients, including 3 present patients with cardiomyopathy, the cardiac symptoms appeared from 4 to 41 years, averaging 17.1 years of age. The mean duration of muscle symptoms was 9 years, ranging from 0 to 33 years. There was no correlation between severity of muscle weakness and cardiomyopathy. Six patients died of heart failure and 3 received cardiac transplantation. Thus there was no characteristic clinical feature in BMD patients with cardiomyopathy except for very poor prognosis. Since the myocardial involvement is not related with clinical severity and duration of the disease, careful observation for cardiac function should be carried out in all BMD patients even in the early stage of muscle weakness. PMID- 2265505 TI - [Somatosensory evoked potentials in patients with hypoxic coma--correlation with neurologic prognosis]. AB - Somatosensory evoked potentials to median nerve stimulations were recorded in 21 patients with hypoxic coma within 24 hours from the onset. According to the neurologic prognosis, the patients were classified into 4 groups, such as I, complete recovery (5 patients), II, partial recovery (3 patients), III, vegetable state (8 patients), IV, brain death (5 patients). Measurements performed include central conduction time (N13-N20 interpeak latency) and amplitude ratio between N20 and P25. As N20 and P25 disappeared in 3 of 8 vegetable patients and all of brain death patients, disappearance of these waves indicates poor neurologic prognosis. Central conduction time showed no significant difference. Amplitude ratio between N20 and P25 (P25/N20) revealed significant decrease in vegetative patients for normal control subjects, complete recovery and partial recovery patients (p less than 0.05). Measurement of this ratio in early phase is useful to predict neurologic outcome in patients with hypoxic coma. PMID- 2265506 TI - [Hereditary progressive dystonia with marked diurnal fluctuation--a report of two siblings, one of them showing age-dependent changes of symptoms]. AB - Two siblings of hereditary progressive dystonia with marked diurnal fluctuation are reported in this communication. The case 1 is a 50-year-old woman who developed dystonia in the right lower extremity at the age of 8 which deteriorated in the afternoon. At the age of 13 she became unable to walk in the afternoon because of dystonia, but after the age of 23 her symptoms began to ameliorate and at the age of 29 her daily activities became no longer disturbed by dystonia even in the evening. However, at the age of 42 dystonia in the lower extremities began to worsen again toward the end of the day and after the age of 47 dystonia appeared in the all extremities. Since the age of 49 she had been able to walk only for three hours after awakening. Her 37-year-old half sister, case 2, also developed a slight dystonia in the left upper extremity at the age of 8. At the age of 33 she felt tight in the neck, waist and extremities after hard works in the evening, and the worst of it was in the left arm which would not move. Both cases were well responsive to L-dopa. Their family history revealed that their father had a history of dystonia the course of which was similar to that of the case 1. Dominant inheritance could be considered in this family. These findings would suggest that hereditary progressive dystonia with marked diurnal fluctuation could show not only a diurnal fluctuation but also age dependent changes of symptoms. Its basic abnormalities might exist in the dopamine storage pool. PMID- 2265507 TI - [Familial idiopathic vitamin E deficiency associated with cerebellar atrophy]. AB - Sibling cases of familial vitamin E deficiency accompanied by ataxia, polyneuropathy and mental retardation were reported. Case 1 was a 37-year-old male who developed progressive gait disturbance, deformity of the feet and head tremor from childhood, after normal delivery and development of early childhood. On physical examination, he had cataract, high arched palate and pes cavus. Neurological examination revealed mental retardation (WAIS 68), scanning speech, muscular atrophy of the face and extremities with predominance in the lower limbs, absent Achilles tendon reflex, disturbance of superficial and deep sensation predominant in distal limbs, and marked gait ataxia. Ataxia was both cerebellar and sensory in nature. Laboratory data of the blood showed no significant abnormalities including blood glucose and vitamin B12 except a markedly low level of serum vitamin E. The brain CT scan revealed severe cerebellar atrophy and marked dilatation of the cisterna magna and the subarachnoid space around the cerebellum. Motor nerve conduction velocity in the leg was decreased. Biopsy specimen from the quadriceps muscle showed neurogenic atrophy. Sural nerve biopsy revealed decrease in large myelinated fibers with axonal degeneration and regeneration. Oral administration of alpha-tocopherol acetate, 600 mg per day, diminished ataxia significantly. Based on lysosomal enzyme activity in leukocytes, clinical and laboratory examination, lipidosis or spinocerebellar degeneration was excluded. Chronic lipid malabsorption or beta lipoprotein deficiency which can cause decrease in vitamin E absorption, was not recognized. On oral loading with 2 g of alpha-tocopherol acetate, the decrease rate of serum vitamin E was normal. Consequently the low vitamin E was considered to have resulted from selective impairment of vitamin E absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265508 TI - [The role of magnetic resonance imaging in the diagnosis of Hallervorden-Spatz disease]. AB - A mentally-retarded 21-year-old female with narrowing of the visual field was admitted to our hospital because of dystonia in the body and extremities which appeared 6 months before and was gradually exacerbating. On admission, torsion dystonia, pyramidal tract sign, and retinitis pigmentosa with optic atrophy, urinary incontinence, hyperhidrosis and insomnia were noted. On the Wechsler Adult Intelligence Scale, she achieved less than 60 for verbal-IQ. Laboratory tests including serum copper and ceruloplasmin, were all normal. A computed tomography of the brain showed small hyperdense spot in the globus pallidus on the both sides. There was neither cortical atropy nor ventricular dilatation. A Magnetic Resonance Imaging was obtained using both moderate-field (0.5 Tesla) and high-field (1.5 Tesla) superconducting MR systems. T2-weighted spin echo images demonstrated markedly decreased signal intensity area restricted in the globus pallidus and substantia nigra on both system. Moreover, in the center of the globus pallidus, a small high signal spot was seen ("eye-of the-tiger" sign coined by Sethi et al). There was no abnormal signal in the putamen, caudate nucleus, red nucleus, and dentate nucleus. On the other hand, T1-weighted inversion recovery images were not remarkable. These striking low attenuation on T2-weighted findings suggests an increased iron deposition limited to the globus pallidus and substantia nigra which is characteristic of Hallervorden-Spatz disease/syndrome (H-S). Moreover, "eye-of-the-tiger" sign on T2-weighted MR images in the globus pallidus is previously described in H-S.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265509 TI - [Parkinsonism associated with cerebrotendinous xanthomatosis]. AB - Two sibling cases of cerebrotendinous xanthomatosis with parkinsonism were reported. One was a woman of 39 years old, and another was her sister of 36 years old. In both cases, febrile convulsion appeared on 1.5 year old, and mental deterioration, ataxic -spastic gait, cataract and swelling of Achilles tendons developed in order since entrance into elementary school. Five years ago, while they were in hospital at the first time, they were diagnosed as cerebrotendinous xanthomatosis by mental disturbance, cerebellar ataxia, pyramidal tract sign, histologically xanthomatous granuloma of Achilles tendons and hypercholestanolemia and family history of autosomal recessive trait. After the second admission, parkinsonism was noticed in addition to those findings above. Parkinsonism consisted of the following: Resting tremor of parkinsonian type, mild muscle rigidity of forearm and intrinsic-plus hand were observed in the elder sister, and generalized severe rigidity and bradykinesia in the younger sister. In both cases, brain CT showed the pontocerebellar atrophy, and the bilateral low density area in corona radiata, posterior portion of internal capsule, cerebral peduncle, tegmentum of midbrain and deep matter of cerebellum. Brain MRI also showed abnormal intensity in the same regions as on the brain CT. Administration of anti-parkinsonian drugs was challenged for the parkinsonism. Oral L-dopa test (500 mg) moderately improved parkinsonism in both cases. Therapy of diphenylpyraline hydrochloride (10 mg/day) entirely inhibited parkinsonian tremor and mild rigidity in the elder sister but was less effective for severe rigidity in the younger sister than administration of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265510 TI - [Systemic lupus erythematosus presenting chronic relapsing polyneuropathy as the first manifestation without auto-antibodies]. AB - Chronic relapsing polyneuropathy (CRPN) is an idiopathic disorder characterized by relapsing and remitting course, elevated CSF protein, slow nerve conduction and absence of systemic disease(s). Systemic lupus erythematosus (SLE), however, has been reported to manifest clinical symptoms and signs mimicking CRPN. A few authors described CRPN as a presenting manifestation or more rarely as the only illness of SLE. In these cases diagnosis of SLE was confirmed by some laboratory tests to detect auto-antibodies which were positive in subclinical SLE. We experienced a 24-year-old female whose illness started as CRPN without any auto antibodies and recurred with autoimmune abnormalities indicating SLE. She noticed muscle weakness in the lower extremities about ten months previous to the first admission. The weakness progressed gradually and was accompanied by urinary incontinence and sensory deficits in limbs. In another hospital lumbar puncture revealed highly elevated CSF protein and she was referred to us. Neurologic examination showed sensorimotor polyneuropathy with normal blood chemistry and negative auto-antibodies. Prednisolone therapy brought out gradual improvement. She was readmitted 2 years after the first admission because of severe motor dominant polyneuropathy. Serological examination revealed positive auto antibodies including antinuclear (ANA), anti-DNA, anti-RNP and anti-ENA antibodies. CBC showed decreased number of white blood cells. Nerve conduction velocities were markedly reduced. Again prednisolone was administrated successfully. Thereafter, she experienced several relapsing and remitting cycles. It was characteristic that deterioration of symptomatological findings such as motor weakness was always accompanied by an elevated titer of ANA and increased CSF protein in each of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265511 TI - [An acute axonal form of Guillain-Barre syndrome with antibodies against gangliosides GM1 and GD1b--a case report]. AB - We reported a case of Guillain-Barre syndrome with autoantibodies against gangliosides GM1 and GD1b, which has not been reported yet. A 25-year-old man was admitted with a 7-day history of acute progressive weakness in the extremities. Two weeks before admission he had suffered from an episode of watery diarrhea. Neurological examination revealed areflexia and tetraparesis without any sensory impairment. Respiration and cranial nerves were not involved. The CSF protein level was 157 mg/dl with normal cellularity on the 14th illness day. The maximum M potential amplitude was 0.1 mV, which was 2% of the lower limit of normal, whereas motor and sensory nerve conduction velocities were normal on day 22. Repeated electrophysiological studies suggested that the predominant process was axonal degeneration. Although he received plasmapheresis at the acute phase, four months after onset he continued to have distal dominant limb weakness with wasting. High-performance thin-layer chromatography with immunostaining revealed that his serum IgG reacted with GM1, GD1b, and asialo-GM1. Enzyme-linked immunosorbent assay showed that anti-glycolipids antibodies titers decreased, concurrent with clinical course. Immunoabsorption study demonstrated that antibodies with anti-GM1 activity were absorbed with liposomes containing purified GD1b, indicating that autoantibodies bind to the galactosyl (beta 1-3) N acetylgalactosaminyl moiety which is shared by GM1, GD1b, and asialo-GM1. There have been several reports of lower motor neuron diseases with monoclonal IgM antibody to GM1, GD1b, and asialo-GM1. This case suggested that the transient rise in these anti-carbohydrate antibodies may be involved in the pathogenesis of acute axonal degeneration of motor nerve as well as paraproteinemic motor neuron diseases. PMID- 2265512 TI - [Central neurogenic hyperventilation in an awake patient with a primary cerebral lymphoma]. AB - We described clinical and neuropathological findings of a case of primary cerebral lymphoma with central neurogenic hyperventilation (CNH). A 54-year-old awake woman with a primary cerebral lymphoma presented hyperventilation for two weeks. Arterial blood gas showed severe respiratory alkalosis; PH 7.603, PaCO2, 10.5 mmHg, PaO2 129.8 mmHg, HCO2 10.4 mmol/L, BE -8.0, O2SAT 98.9%. Rebreathing from a paper bag, and intravenous administration of diazepam and sodium bicarbonate failed to alter the respiratory pattern. Consecutive CAT scans indicated that CNH didn't occur when the tumor extensively invaded the cerebral cortex, cerebellum, thalamus and basal ganglia but was initiated when the lymphoma invaded the brain stem. Pathological study showed lymphoma cells invaded the cerebral cortex, cerebellum, thalamus and basal ganglia severely, and the brain stem moderately and recently. Contrary to the cases reported by Plum, Lange and Bateman, the lower medulla was also involved. Possible mechanisms for CNH are discussed in relation to the pathological findings and consecutive CAT scan findings. PMID- 2265513 TI - Effect of a program to facilitate parent-child communication about sex. AB - U.S. teens have high rates of premarital sexual activity resulting in alarming rates of teenage pregnancy and sexually transmitted disease. One possible way to combat the problem of teenage sexual activity is to promote sexuality education within the family. The purpose of this study was to increase parent-child communication about sex through an educational program for parents. The effect of the educational program was evaluated by a nonrandomized, controlled trial. Volunteer parents were recruited from three middle schools (grade six through eight) located in middle to upper-middle socioeconomic class neighborhoods. The parents participated in four 2-hour sessions which included factual information about sexuality and exercises to improve communication skills. The experimental group (N = 47) were requested to fill out questionnaires immediately before and one month after the program. The control group (N = 17) were requested to fill out questionnaires one month before and again immediately before the program. Parents were asked to report the number of times they talked with their adolescents about 11 sex-related topics. The difference in reported frequency of communication before and after the program was compared using a two-tailed, matched pairs t-test. Twenty-four (51%) experimental group parents and eight (47%) control group parents completed both questionnaires. There was a significant increase in communication reported by the experimental group. The mean difference of the number of topics discussed was 10.9 (SD 7.3) for participants versus -2.5 (SD 5.9) for controls (p = .00053). This study shows that parent-child communication about sex can be facilitated by an educational program for parents. PMID- 2265514 TI - Once-daily intramuscular ceftriaxone in the outpatient treatment of severe community-acquired pneumonia in children. AB - Ceftriaxone, a broad spectrum third-generation cephalosporin with a half-life of six to eight hours, was evaluated prospectively in 147 children with severe community-acquired bacterial pneumonia during the period 11/15/88-5/15/89. Thirty nine of the children had been unsuccessfully treated with vanous oral antibiotics prior to admission [corrected]. All the patients were initially hospitalized and started on once a day intramuscular ceftriaxone. Mean duration of ceftriaxone therapy was five days. Pathogens were recovered from blood cultures of 17 (11.6%) patients and included S. pneumoniae (13 patients), H. influenzae (three, all resistant to ampicillin) and S. viridans (1) [corrected]. All isolates were sensitive to ceftriaxone. An additional patient had L. pneumophila diagnosed by serology. Cure was achieved in 142 (96.6%) patients; improvement was usually observed within 24-48 hours. After 48 hours, 121 (82.2%) children could be discharged and continued the therapy on ambulatory basis. Based on previous experience we estimated that 383 hospitalization days were saved. No serious side effects were observed. Five patients were considered therapeutic failures; two of them developed empyema and one of them required repeated drainage procedures. A third patient experienced a relapse of pneumonia shortly after completion of therapy. The other two remained febrile for more than seven days; their subsequent improvement was unrelated to the antibiotic therapy, suggesting a viral or mycoplasmal syndrome. Our data suggest that once daily intramuscular ceftriaxone can be successfully used for the outpatient treatment of most community-acquired severe bacterial pneumonias in children. In our opinion it represents the treatment of choice for patients who failed treatment with other antimicrobials and are clinically stable enough not to require hospitalization. PMID- 2265515 TI - The use of ceftriaxone for bacterial pneumonia in pediatric patients. PMID- 2265516 TI - Management of smooth-blunt gastric foreign bodies in asymptomatic patients. AB - Guidelines for management in the asymptomatic patient with a smooth-blunt gastric foreign body are not well established in the pediatric literature. Questionnaires were sent to pediatricians, family practitioners, pediatric gastroenterologists and pediatric surgeons with an over-all response rate of 62.2%. There was no agreement in regard to how long one should observe such patients before recommending intervention. There was no correlation of years of clinical experience and length of observation recommended either. Review of the pre endoscopic literature revealed spontaneous evacuation in 93-99% of all types of foreign bodies in 1477 pediatric patients. An observation period of at least eight weeks should be strongly considered in an asymptomatic patient with a smooth-blunt gastric foreign body. Exceptions would include an anatomic abnormality of the gastric outlet, previous gastric outlet surgery as well as a possibly toxic object. PMID- 2265517 TI - Very low birth weight infants-educational outcome at school age from parental questionnaire. AB - Educational outcome of former very low birth weight infants, greater than or equal to 1250 g., were obtained by a questionnaire mailed to the families' last known address. Fifty-seven infants were known to have survived the first year of life and an address was available for 49 families, 51 infants (two sets of twins). Forty families (82%) responded regarding 42 of the 57 infants (74%). Only one child had a major health problem, cerebral palsy and epilepsy. All the children were in school. Thirty-nine (93%) were in a regular class and three (7%) were in special classes. Twenty-six children (67%) in a regular class did not require special educational assistance, 13 (33%) did. Using the Hollingshead Four Factor Index, socioeconomic status affected outcome P = 0.0068 (Fischer's exact test). There were 20 children in Classes I-III, upper socioeconomic and three children Class IV-V, lower socioeconomic, requiring no special education and six children in Class I-III and eight children in Class IV-V requiring special education. The neonatal risk factors birth weight, gestational age, appropriateness of weight for gestation, Apgar score, time to regain birth weight, and time on mechanical ventilation did not affect outcome. The only neonatal risk which was significantly different between the respondents and nonrespondents was birth weight, P less than 0.020 for the children in a regular class without assistance and P less than 0.005 for children in a regular class with assistance. Overall, 40 percent of the children had repeated a grade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265518 TI - When should renal biopsy be done? An illustrated discussion of indications, pathologic changes, and usefulness for differential diagnosis and management. PMID- 2265520 TI - Is supplemental water necessary for breast-fed babies? PMID- 2265519 TI - Pancreatic fracture secondary to child abuse: the role of computed tomography in its diagnosis. PMID- 2265521 TI - Hyperlipidemia as a complication of Niemann-Pick type B disease. PMID- 2265522 TI - Group A streptococcal supraglottitis. PMID- 2265523 TI - Survival after bilateral congenital diaphragmatic hernia. PMID- 2265524 TI - Influenza: a preventable disease finally being prevented in Colorado. PMID- 2265525 TI - November: diabetes month. PMID- 2265526 TI - Alcohol use by physicians. PMID- 2265528 TI - Verb-based versus class-based accounts of actionality effects in children's comprehension of passives. AB - Several studies have shown that children perform worse on tests of passive comprehension when the verb is non-actional than when it is actional. Most existing accounts focus on the semantic characteristics of the class of non action verbs in explaining this difference. An alternative is a "verb-based" account in which passives are initially learned verb by verb, and children hear fewer non-actional passives in their language input. An analysis of the passives heard by Adam, Eve and Sarah (Brown, 1973) found more actional than non-actional passives, consistent with the verb-based account. In a second study, children tested for passive comprehension were re-tested a week later. The verb-based account predicts that children should show a consistent pattern of responses for individual verbs on test and re-test. Such consistency was found, with some inconsistency due to improvement over the re-test. Further analyses showed no effects of affectedness in explaining children's problems with passives. Finally, we discuss whether a mixed model containing both verb-based and class-based mechanisms is required to explain the actionality effects. PMID- 2265527 TI - Higher-order structure and relational reasoning: contrasting analogical and thematic relations. AB - A popular explanation of younger children's success in analogy tasks is that lower-level associative reasoning strategies are used. Younger children are said to have a primarily associative understanding of analogy, with the ability to coordinate sets of relations largely emerging later in development (Goldman, Pellegrino, Parseghian, & Sallis, 1982; Sternberg & Nigro, 1980). One way of testing the associative claim is to pit young children's emergent analogical abilities against thematic (associative) relations, which are known to play an important role in the knowledge structures of young children. The present experiments presented 4-, 5- and 9-year-old children with a:b::c:d analogies in a picture choice format, offering a choice between Analogy and Thematic responses. Only the Analogy responses were correct in terms of the higher-order structure of the analogies. The results showed that the Analogy responses were consistently preferred to the Thematic responses by children of all ages. It is concluded that analogy is an important building block for learning from an early age. PMID- 2265529 TI - Why do young infants fail to search for hidden objects? AB - Recent evidence indicates that infants as young as 3.5 months of age understand that objects continue to exist when hidden (Baillargeon, 1987a; Baillargeon & DeVos, 1990). Why, then, do infants fail to search for hidden objects until 7 to 8 months of age? The present experiments tested whether 5.5-month-old infants could distinguish between correct and incorrect search actions performed by an experimenter. In Experiment 1, a toy was placed in front of (possible event) or under (impossible event) a clear cover. Next, a screen was slid in front of the objects, hiding them from view. A hand then reached behind the screen and reappeared holding the toy. The infants looked reliably longer at the impossible than at the possible event, suggesting that they understood that the hand's direct reaching action was sufficient to retrieve the toy when it stood in front of but not under the clear cover. The same results were obtained in a second condition in which a toy was placed in front of (possible event) or behind (impossible event) a barrier. In Experiment 2, a toy was placed under the right (possible event) or the left (impossible event) of two covers. After a screen hid the objects, a hand reached behind the screen's right edge and reappeared first with the right cover and then with the toy. The infants looked reliably longer at the impossible than at the possible event, suggesting that they realized that the hand's sequence of action was sufficient to retrieve the toy when it stood under the right but not the left cover. A control condition supported this interpretation. Together, the results of Experiments 1 and 2 indicate that by 5.5 months of age, infants not only represent hidden objects, but are able to identify the actions necessary to retrieve these objects. The implications of these findings for a problem solving explanation of young infants' failure to retrieve hidden objects are considered. PMID- 2265530 TI - The what-if of counting. PMID- 2265531 TI - Paralogical reasoning: Evans, Johnson-Laird, and Byrne on liar and truth-teller puzzles. AB - People's performance on knight/knave problems is deliberate. They make assumptions, draw deductive inferences from them, and evaluate the consequences of these inferences. In an initial paper on this topic (Rips, 1989), I proposed a model for a subset of such problems that depend on sentential reasoning. The main component of the model is a set of natural-deduction rules, drawn from prior work on propositional inference. This natural-deduction framework seems well suited to explain the reasoning that subjects display on these problems, since it incorporates a mechanism for making assumptions and following them up. Moreover, the number of assumptions and rule applications needed to solve a problem yields an intuitively appealing measure of how difficult the problem should be. In accord with this prediction, the experiments found increases in error rates and reaction times as a function of the assumptions-plus-inferences measure. In their note, Johnson-Laird and Byrne sketch a possible alternative. Their account posits five processing strategies tailored to this problem domain and a mechanism for evaluating sentential arguments based on mental models. The mental-model component is a variation on the usual truth-table method, where individual models correspond to truth-table rows. The main prediction of this component is that the more models subjects must consider, the harder the problem. However, the experiment reported here found no evidence for this prediction. Problems with larger numbers of models do not yield higher error rates than those with few. What does cause difficulties for subjects is scope relations among connectives, a fact that inference-rule theories can easily explain. Given these findings, it's not surprising that the predictive burden for knight/knave problems must be carried by Johnson-Laird and Byrne's strategies, rather than by mental models. These strategies control the order in which subjects consider parts of the problem, and they provide possible stopping points. There are, however, several difficulties with these strategies. Of their four new strategies, Johnson-Laird and Byrne offer no evidence at all for two of them. Of the remaining two, only one accounts for a significant proportion of the variance when allowance is made for confounding variables. Moreover, all four strategies are ad hoc, rather than being derived from some more general theory. Certainly, much remains to be done in filling out the picture of how such problems are handled, as both Evans and Johnson-Laird and Byrne point out.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2265532 TI - Correlates of DSM-III personality disorder in obsessive-compulsive disorder. AB - Forty-three patients with primary obsessive-compulsive disorder (OCD) completed the Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to assess axis II personality disorders (PD) from DSM-III. Results showed that 53% of the patients received at least one PD diagnosis. The most frequent diagnoses were avoidant (30%), histrionic (26%), dependent (19%), and schizotypal (16%). Consideration of the personality traits irrespective of diagnostic category showed that in addition to avoidant and dependent personality characteristics, the sample had strong passive aggressive and compulsive tendencies and substantial histrionic, paranoid, and schizotypal traits. Patients exhibiting a greater number of personality traits were also significantly more symptomatic. However, anxiety, phobic, and obsessive-compulsive symptoms were not selected as unique predictors of any personality variables in the regression analyses. Rather, the most important correlate of PD in these patients consisted of dysphoric mood as assessed by the Beck Depression Inventory (BDI) and, to a lesser degree, younger age or shorter duration of illness. These findings do not support a specific link between OCD and PD in general and compulsive PD in particular. PMID- 2265533 TI - Predicting outcome for borderline personality disorder. AB - The purpose of this study is to identify variables predictive of the psychosocial outcomes of borderline patients 2 years following an acute psychiatric hospitalization. Of the initial 88 inpatients scoring positive for the Diagnostic Interview for Borderlines (DIB), 65 (73.8%) were reinterviewed, 14 (15.9%) refused, five (5.7%) were unable to be located, and four (4.6%) suicided. The dropouts (n = 19) were significantly more likely to be single, separated, or divorced, to be male, and to be diagnosed as having co-existing antisocial personality disorder than the followed-up probands (n = 69). In terms of global functioning, over the 2-year follow-up period, 61 (87.7%) of the 69 probands were judged to be functioning normally less than 50% of the follow-up interval. Using logistic regression, two variables, initial impulse action scores and poor premorbid functioning, predicted poor versus good outcome. This study supports the literature, which indicates that the early course of borderline personality disorder (BPD) is stormy. Impulsivity and poor premorbid functioning may be predictive of poor short-term outcome in borderline patients. PMID- 2265534 TI - Personality disorders in recent-onset bipolar disorder. AB - The frequency and types of DSM-III personality disorders (PDs) were investigated in a sample of 26 recent-onset bipolar-disordered (BD) patients. Results showed that 62% of BD patients had PDs according to the Structured Interview for DSM-III Personality Disorders (SIDP). The most frequently diagnosed PDs were the histrionic, borderline, passive-aggressive, and antisocial categories. A comparison between the BD patients and a sample of 35 recent-onset schizophrenic patients showed significant differences for two PDs. Schizotypal PD was more frequently diagnosed in the schizophrenic group, while the BD group had a higher frequency of histrionic PD. PMID- 2265535 TI - Schizotypal features in obsessive-compulsive disorder. AB - This study examined the prevalence and nature of schizotypal features in obsessive-compulsive disorder (OCD). Although this symptom pattern has been related retrospectively to treatment resistance, no prospective data have addressed such an hypothesis. This study sets the stage for further work in this arena by prospectively identifying and characterizing a schizotypal subset of OCD patients. Twenty-eight percent of the sample had schizotypal features, although only 8% met criteria for schizotypal personality disorder. Social-evaluative concerns and psychotic-like symptoms characterized this subgroup. Schizotypal patients did not differ from nonschizotypes with regard to anxiety, depressive, or obsessive-compulsive symptoms. PMID- 2265536 TI - The nosology and prognosis of puerperal psychosis: a review. AB - Functional psychosis in the puerperal period is a dramatic phenomenon that presents a unique set of diagnostic and therapeutic challenges. Despite its omission from modern classificatory systems such as DSM-III and DSM-III-R, the concept of puerperal psychosis continues to receive support from clinicians on the basis of the apparently distinctive clinical picture that characterizes psychoses occurring at this time. The range of possible nosological models is considered in light of relevant studies of puerperal illness, and the evidence for and against each model is presented. The question of the prognosis of puerperal psychosis is reviewed and guidelines for its estimation in the individual case proposed. The heuristic importance of puerperal psychosis in terms of basic research and preventive psychiatry is also stressed. PMID- 2265537 TI - Sleep disturbance and computerized axial tomographic scan findings in former prisoners of war. AB - Ten drug-free former American prisoners of war (POWs), captured on Bataan and Corregidor by the Japanese in World War II, participated in a study of the relationship between structural brain abnormalities on computerized axial tomographic (CT) scans and sleep electroencephalographic (EEG) findings. All subjects had complaints of sleep disturbances and other posttraumatic stress disorder (PTSD)-related symptoms. Six of 10 subjects had no stage 4 sleep, and had significantly higher mean ventricular brain ratios (VBRs). Structural brain measures such as VBRs and global sulcal widening (GSW) correlated significantly with the number of awakenings; GSW also correlated significantly with time spent asleep. However, because data from normal age-matched controls are not available, it remains to be seen whether our findings are PTSD specific. PMID- 2265538 TI - Career choices in psychiatry: the evolution from resident to practitioner. AB - There exists very little data on how graduating psychiatry residents make practice choices. By reviewing the psychodynamic and institutional themes that emerged in a Career Planning Seminar taught at The New York Hospital-Cornell Medical Center over the past decade, the authors hope to provide new information about this important developmental task. In addition, the ways in which trainees perceive specific career options will be described. PMID- 2265539 TI - Diagnostic subgroups of antisocial alcoholics: outcome at 1 year. AB - Of 233 alcoholics initially evaluated and subdivided into groups with an additional diagnosis of antisocial personality disorder (ASP) only (N = 38), ASP plus drug abuse (N = 30), ASP plus major depressive disorder (N = 18), and those with no additional diagnosis (N = 147), 205 were followed up 1 year later. The ASP plus drug group, although younger and having fewer years of alcoholism, did worse in the 1-year follow-up on many indicators of alcoholism severity compared with the other antisocial groups and the alcoholism only group. The ASP plus depressed group demonstrated marked improvement on measures of psychopathology and alcoholism severity over the course of 1 year such that they were comparable on these measures at 1-year follow-up to the other antisocial groups. These findings may indicate that the ASP/drug alcoholic has a poor long-term prognosis compared with the ASP only alcoholic, while the ASP/depressed patient has a disorder comparable in prognosis to the ASP only alcoholic. PMID- 2265540 TI - A contribution to the discussion of the role of the genetic factor in suicide, based on five studies in an epidemiologically defined area (Province of Salzburg, Austria). AB - The question of what role genetic factors have in the transmission of suicidal behavior, in particular suicide itself, is discussed on the basis of five studies of an epidemiologically clearly defined region (the Province of Salzburg, Austria). The high percentage of suicide-positive family histories as compared with the literature is due to exceptionally good sources of information. It could be shown that in suicide cases also suffering from endogenous depression, both endogenous psychoses and suicides appeared to a greater extent in their families. However, in contrast to current assumptions, the suicide disposition is not just found in those with endogenous psychoses, but shows a separate genetic determination. The author concludes that the genetic factor in suicide research and in the evaluation of suicidality should be considered equally along with psychodynamic and sociodynamic factors. PMID- 2265541 TI - Beta-carotene and cancer prevention: what is the evidence? AB - A growing body of literature supports a possible role for beta-carotene in the prevention of human cancer. The most scientifically rigorous method for testing the hypothesis that beta-carotene has chemopreventive properties is with intervention trials, several of which are ongoing or soon to be initiated. Connecticut will be actively involved in three of these trials. This article reviews and critically evaluates the evidence supporting a role for beta-carotene in the prevention of human cancer, including animal studies, cell culture studies, epidemiologic studies, and intervention trials, and concludes with a brief description of chemoprevention research involving beta-carotene in Connecticut. PMID- 2265542 TI - A case of L-tryptophan-induced eosinophilia-myalgia resulting in death. AB - A syndrome of eosinophilia and myalgias associated with the ingestion of L tryptophan has recently been described. In a large majority of the cases reported to the Centers for Disease Control thus far, discontinuation of L-tryptophan consumption has resulted in complete resolution of symptoms. The author presents a case of L-tryptophan-induced eosinophilia-myalgia syndrome which was progressive despite discontinuation of the L-tryptophan. The condition was refractory to treatment and ultimately resulted in the death of the patient. PMID- 2265544 TI - Coping with the stress of malpractice litigation. CMIC Defendant Support Program. PMID- 2265543 TI - Pulmonary Kaposi's disease diagnosis by transbronchial biopsy. AB - While Kaposi's sarcoma (KS) classically present with rather typical skin lesions in elderly Jewish and Italian males, visceral lesions are also well documented. More recently the occurrence of this disease in patients with the acquired immune deficiency syndrome (AIDS) is being recognized with increasing frequency. The difficulty in diagnosing pulmonary involvement in these patients is complicated by the nonspecific clinical and radiologic presentation which may mimic opportunistic infection. Tissue diagnosis is invaluable in such instances but controversy exists as to whether such diagnosis can be reliably made by transbronchial biopsy in lieu of open lung biopsy. The authors report a case in which a patient with AIDS was diagnosed as having pulmonary KS on the basis of a transbronchial biopsy. The clinical and histologic findings are described and the pertinent literature is reviewed. PMID- 2265545 TI - Comments on the status of laws relating to treatment of incompetent patients. PMID- 2265546 TI - Adjuvant therapy for patients with colon and rectal cancer. National Institutes of Health. PMID- 2265548 TI - Comments on physical examination. PMID- 2265547 TI - The IOM report and public health. AMA Council on Scientific Affairs;. AB - A recent Institute of Medicine report defined "public health" as what society must do to keep people healthy and further defined it as involving the collection of data, assessment of problems, and assurance of health protection. Public health professionals include physicians, nurses, sanitarians, biostatisticians, engineers, and administrators, and epidemiology is public health's basic science. Past successes in the United States, such as increases in longevity and decreases in infant mortality and cardiovascular death rates, demonstrate that progress is possible; however, inequalities persist, for example, in infant mortality rates and availability of medical care to lower socioeconomic groups. The major responsibilities of public health departments include leading and coordinating public health efforts, controlling epidemics, carrying out disease and injury surveillance, collecting vital statistics, ensuring good medical and dental care for the indigent, environmental control, health education, and laboratory services. PMID- 2265549 TI - Reductionist biology and population medicine--strange bedfellows or a marriage made in heaven? PMID- 2265550 TI - The middle class and the old morality. PMID- 2265551 TI - Minors and abortion revisited. PMID- 2265552 TI - Cytogenetic analysis of human solid tumors by in situ hybridization with a set of 12 chromosome-specific DNA probes. AB - We have applied fluorescent in situ hybridization (FISH) to assess the presence of numerical chromosome aberrations in fresh specimens of human solid tumors of varying histology. For this purpose, a set of 12 biotinylated chromosome specific, repetitive alpha-satellite DNA probes (for chromosomes 1, 6, 7, 9, 10, 11, 15, 16, 17, 18, X and Y) were hybridized directly to isolated interphase nuclei. Utilizing this approach, we found numerical chromosome changes in all tumors. FISH ploidy profiles were in accordance with flow cytometric DNA histograms of these tumor cells. PMID- 2265553 TI - Detection of the Philadelphia chromosome in interphase nuclei. AB - Double fluorescence in situ hybridization was used to detect Philadelphia (Ph) chromosomes in interphase nuclei and metaphases of patients with chronic myeloid leukemia. Application of cosmid probes for 3' ABL and 5' BCR sequences gave better results than libraries for chromosomes 9 and 22. The present approach may provide an alternative method for monitoring minimal residual disease in Ph+ CML patients. PMID- 2265554 TI - Immunocytogenetics. VI. A nonhistone antigen is cell type-specially associated with constitutive heterochromatin and reveals condensation centers in metaphase chromosomes. AB - We report a nonhistone antigen to be cell type-specifically associated with constitutive heterochromatin. Human autoantibodies were used to analyze by indirect immunofluorescence the pattern of association of the antigenic protein with the heterochromatin of murine chromosomes, as well as those of other representative vertebrate species. The evolutionary stability of its cell type specific distribution pattern suggests that this nonhistone antigen plays an important role in the structure and/or function of constitutive heterochromatin. In mitotic chromosomes, the antigen was localized to discrete granules scattered throughout the entire chromatin. These structural elements may function as condensation centers, with each granule representing an aggregation of anchoring complexes for the chromatin loops. PMID- 2265555 TI - Cell proliferation in chorionic villi at different gestational ages, as analyzed by premature chromosome condensation. AB - The technique of premature chromosome condensation (PCC) was adapted to human first-trimester chorionic villi cells to analyze the cell-cycle kinetics of interphase chromatin. Uncultured cells of the cytotrophoblast (CT) and the mesenchymal core (MC) were obtained by a two-step digestion. PCC was induced by fusion of the chorionic interphase cells with mitotic Chinese hamster ovary or HeLa cells. Cells showing PCC in G1 (classes 1-6), S, and G2 were found. To analyze further the proliferation stages of chorionic G1 interphases, the proliferation potential index (PPI) of 34 placentae recovered between the 8th and 12th week of gestation was determined. The mean PPI found in the CT and MC cells ranged from 18% to 73%, values similar to those described for intensely proliferating tissues. The highest mean PPI value (73%) was observed in CT cells from placentae recovered at the 9th week of gestation, indicating a high specific proliferative activity of CT cells at this developmental stage. PMID- 2265556 TI - Fine mapping of the long arm of human chromosome 11 by in situ hybridization using different translocations, including the t(11;22) of Ewing sarcoma. AB - The progesterone receptor gene (PGR), the gene coding for porphobilinogen deaminase (PBGD), the gene coding for a neural cell adhesion molecule (NCAM), the oncogene ETS1, and the anonymous genomic sequence D11S29 have been previously located on the long arm of chromosome 11. However, gene localizations obtained with different gene-mapping procedures have led to occasional discrepancies. To localize these genes more precisely, we hybridized five human DNA sequences with different chromosomal rearrangements, including four balanced and one unbalanced translocations. We show here that the order of these five sequences is cen-PGR PBGD-DIIS29/NCAM/ETS1-tel. PMID- 2265557 TI - Regional assignments of the zinc finger Y-linked gene (ZFY) and related sequences on human and mouse chromosomes. AB - Recent chromosome walking experiments have identified a candidate gene (ZFY) for the testis-determining factor on the human Y chromosome (Page et al., 1987). We report here the regional assignments of the ZFY gene and related sequences in the human and the mouse. By in situ hybridization, we assigned ZFX and ZFY to human chromosome bands Xp21 and Yp11.3, respectively. Although the mouse harbors two Zfy genes, only one site at band A1 of its Y chromosome was significantly labeled. The mouse Zfx gene and the Zfa gene on chromosome 10 were assigned to bands XD and 10B5, respectively. These assignments of the ZFX gene in human and mouse add another marker to the conserved syntenic group for evaluating the evolutionary relationship of the human and mouse X chromosomes. PMID- 2265558 TI - Localization of human calcyphosine gene (CAPS) to the p13.3 region of chromosome 19 by in situ hybridization. PMID- 2265559 TI - Assignment of the human calpastatin gene (CAST) to chromosome 5 at region q14--- q22. AB - The human calpastatin gene (CAST) was assigned to chromosome 5 by spot-blot hybridization analysis with flow-sorted chromosomes, and it was further sublocalized to bands 5q14----q22 using in situ hybridization to metaphase chromosomes. PMID- 2265560 TI - The human basic fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25. AB - In situ hybridization was used to localize a cDNA probe for the basic fibroblast growth factor gene (FGFB) to human metaphase and prometaphase chromosomes. In this communication we report the localization of this gene to 4q25. PMID- 2265561 TI - Robertsonian chromosome polymorphism in the Arabian oryx (Oryx leucoryx). AB - A Robertsonian translocation was found in a herd of Arabian oryx (Oryx leucoryx). The translocated chromosome, when analyzed by G-banding, seemed to involve the fusion of chromosomes 17 and 19. The results of C-banding suggested that the fused chromosome is dicentric. The translocation was traced back through two generations and occurred in a total of 8 of 62 animals in the herd. PMID- 2265562 TI - Mapping the gene for murine T-cell growth factor, Il-2, to bands B-C on chromosome 3 and for the alpha chain of the IL2-receptor, Il-2ra, to bands A2-A3 on chromosome 2. AB - Il-2, the gene coding for the cytokine IL2 in the mouse, has been localized by in situ hybridization to bands 3B or 3C on Chromosome 3, where it joins five other genes that also map to 4q in humans. The Il-2 probe also produces a small, secondary grain peak on Chromosome 11, in the vicinity of band 11A5, the significance of which has not yet been determined. The gene for the alpha chain of the IL2 receptor in the mouse, Il-2ra, localizes to bands 2A2 or 2A3 on Chromosome 2. This is the first assignment of a gene located on chromosome 10 in humans to Chromosome 2 in the mouse. PMID- 2265563 TI - Cytogenetic studies of Hynobiidae (Urodela). XI. Banding karyotype of Salamandrella keyserlingii Dybowski and a comparison with those of Hynobius species. AB - C- and R-banding analyses were performed on chromosomes of Salamandrella keyserlingii, in which 20 of 31 chromosome pairs could be identified. Banding patterns were compared between S. keyserlingii and specimens of Hynobius species of the family Hynobiidae. Between S. keyserlingii and six Hynobius species (2n = 56), there were four homoelogous and two partially homoeologous chromosome pairs. Between S. keyserlingii and H. retardatus (2n = 40), there were two homoeologous and two partially homoeologous chromosome pairs. PMID- 2265564 TI - Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome. AB - A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome. PMID- 2265565 TI - Relationship of mouse minor satellite DNA to centromere activity. AB - Chromosomes from a female mouse cell line were identified by Q-banding prior to in situ hybridization with 3H-labeled mouse minor satellite (satellite II) DNA. No cell was found in which every chromosome was labeled, but grain counts showed that every active centromeric region had minor satellite sequences. In the mouse T (10;13)199H translocation, the breakpoint was within the minor satellite array, leaving clusters of minor satellite at the C-bandless active centromere of the 13(10) chromosome and at the interstitial C-band of the 10(13) chromosome, which is not associated with centromeric activity. In a mouse A9 (L-cell derived) marker chromosome with one terminal and two interstitial C-bands, only the terminal C-band was adjacent to an active centromere, but minor satellite DNA was present at all three sites. Minor satellite DNA was not detected on the Y chromosome, although the presence of a small amount of divergent satellite sequences on this chromosome could not be ruled out. PMID- 2265566 TI - Molecular cytogenetic evidence to characterize breakpoint regions in Robertsonian translocations. AB - Four individuals carrying different Robertsonian translocations (13q;14q, 14q;21q, 14q;15q, and 13q;21q) were studied to determine the breakpoints involved in the generation of these derivative chromosomes. Sequential high-resolution G banding, in situ hybridization using alphoid and ribosomal DNA probes, and C banding were performed. In addition, silver staining was also used for visualization of the NOR region. The results provide direct molecular cytogenetic evidence that Robertsonian translocations can take place in different regions in both the short arm and proximal long arm of acrocentric chromosomes. Three different types of breakpoints were identified: between the ribosomal or alphoid sequences, as deduced from the banding and in situ hybridization results, and breaks in two seemingly unrelated regions on the two different chromosomes. The use of conventional cytogenetic techniques together with molecular studies allowed more precise evaluation of the breakpoints involved in Robertsonian translocations than either approach alone might have done. PMID- 2265567 TI - Lampbrush W and Z heterochromosome characterization with a monoclonal antibody and heat-induced chromosomal markers in the newt Pleurodeles waltl: W chromosome plays a role in female sex determination. AB - Two subsets of lateral loops scattered on lampbrush chromosomes of the newt Pleurodeles waltl were characterized. One group was identified by labelling with a monoclonal antibody (A1). The second group was identified by the ability of the loops to be induced by heat treatment. Three loops of each subset were mapped on a short region of the two homologues of lampbrush bivalent IV. These regions appear to be heteromorphic because the six loops are always heterozygous. Five loops are found on one homologue and the sixth on the partner. The distribution of these markers in phenotypic females corresponding to the three sexual genotypes ZW, WW and ZZ shows an absolute correlation of the five loop group with the W chromosome and of the other loop with the Z chromosome. Therefore the heteromorphic regions of the homologues correspond to the differential segments of the heterochromosomes. The identification of a trisomic ZZW female suggests that the W chromosome bears female sex determinants. Furthermore the results show that heat induces loop development and that under normal conditions giant loop development is influenced by the sexual genotype. PMID- 2265568 TI - The heat shock protein hsp70 binds in vivo to subregions 2-48BC and 3-58D of the polytene chromosomes of Drosophila hydei. AB - Multiple interactions of members of the hsp70 family with cellular components have already been described. We present, however, the first evidence that upon heat shock treatment hsp70 molecules interact with specific chromosomal subdivisions of the polytene chromosomes of Drosophila hydei. After a heat shock treatment of 20 min the protein binds to subdivision 3-58D1 and to the heat shock inducible subdivisions 2-48B3-6 and 2-48C1-2. Hsp70 molecules were also observed in subdivision 3-58D1 during recovery at 25 degrees C but not in subdivisions 2 48B3-6 and 2-48C1-2. Our data suggest that this interaction is stress specific. DNase and RNase experiments suggest, moreover, that the hsp70 molecules bind to RNA from ribonucleoproteins (RNPs) in subdivisions 2-48B3-6 and 2-48C1-2 and to DNA in subdivision 3-58D1. The DNA sequences in subdivision 3-58D1 seem to have the potential to adopt the Z-DNA conformation. PMID- 2265569 TI - Intragenomic movement, sequence amplification and concerted evolution in satellite DNA in harvest mice, Reithrodontomys: evidence from in situ hybridization. AB - Three DNA probes isolated from three species of Reithrodontomys (R. montanus, R. megalotis, R. fulvescens) were used to examine within and among species variation in the chromosomal location of satellite DNA and constitutive heterochromatin. These probes hybridized to the centromeric regions on all chromosomes in six species of the subgenus Reithrodontomys. Additionally, nearly all extra centromeric C-band positive regions (with the exception of some heterochromatic material on the X and Y) hybridized to these probes. Within the subgenus Reithrodontomys both the chromosomal distribution and organization of satellite DNA has changed throughout evolution. The evolutionary transition has been from a totally centromeric position in R. fulvescens to centromeric and non-centromeric regions in other species that have undergone extensive chromosomal rearrangements from the primitive karyotype for peromyscine rodents. In addition, the monomer repeat of the satellite sequence differs between R. fulvescens (monomer defined by PstI) and the remaining species in the subgenus Reithrodontomys (monomer defined by EcoRI). These results suggest at least two amplification events for this satellite DNA sequence. Models and mechanisms concerned with the homogenization and spread of satellite sequences in complex genomes are evaluated in light of the Reithrodontomys data. From a phylogenetic standpoint, the satellite sequences composing heterochromatic regions were restricted to the subgenus Reithrodontomys, which supports morphological differences used to recognize two subgenera, Reithrodontomys and Aporodon. Probes failed to hybridize to any part of the karyotype of R. mexicanus (subgenus Aporodon) or to seven species from other closely related genera (Baiomys, Neotoma, Nyctomys, Ochrotomys, Onychomys, Peromyscus, Xenomys), some of which are considered as potential sister taxa for Reithrodontomys. PMID- 2265570 TI - Meiotic chromosome behaviour reflects levels of sequence divergence in Sus scrofa domestica satellite DNA. AB - We present a general model for the evolution of chromosome-specific satellite DNA subfamilies. Sus scrofa domestica has a bimodal karyotype with two autosomal subsets of 12 meta-/submetacentric (Mc) and 6 acrocentric (Ac) chromosome types (Mc and Ac "subgenomes"). We show that the centromeric heterochromatin is characterised by two distinct satellite DNA families designed Mc1 and Ac2. Mc1 is a diverse satellite family of the Mc subgenome of which certain members with a 100 bp repeat unit are found to occur at the pericentromeric regions of each Mc autosome, while others are chromosome-specific, e.g. clone Mc pAv1.5, a higher order repeat variant, which hybridises specifically to chromosome 1. Ac2 is a homogeneous satellite occurring at the subterminal pericentromeric regions of all Ac autosomes. DNA sequence analyses showed that all clones investigated are built up from a 14 bp repeat unit which is highly conserved. In situ hybridisation to meiotic pachytene nuclei revealed a distinct spatial arrangement of the Ac2 centromeric satellite. PMID- 2265571 TI - Distribution of CT-rich tracts is conserved in vertebrate chromosomes. AB - The distribution of d(CT)-rich pyrimidine tracts in the karyotypes of a variety of vertebrates was studied by in situ hybridization. The probe for these studies was a 56bp homopyrimidine/homopurine sequence obtained from a mouse genomic library constructed with DNA prepared from a restriction enzyme digestion of metaphase chromosomes. Single-stranded DNA nuclease digestions and two dimensional gel analysis of topoisomers of this sequence indicated that it is capable of adopting a triplex conformation in vitro. In situ hybridization with this probe to the karyotypes of ten different vertebrate species revealed a highly conserved chromosomal distribution of d(CT)-rich tracts. These tracts are found throughout the chromosomal arms and in some karyotypes they are clustered, producing a banding pattern. However, at the resolution of the light microscope these tracts appeared to be absent from the centromeric regions of all chromosomes examined except those of chicken. The non-random distribution of these tracts to the chromosomal arm regions implies an organizational or functional role for this repeat class. It is unlikely that the 56 bp sequence type contributed to the formation of the triplex DNA structure previously detected in centromeric domains of mouse. PMID- 2265572 TI - Synapsis in single and double heterozygotes for partially overlapping inversions in chromosome 1 of the house mouse. AB - Electron microscopic (EM) analysis of synaptonemal complexes (SC) in single and double heterozygotes for the partially overlapping inversions In(1)1Icg, In(1)1Rk and In(1)12Rk in chromosome 1 of the house mouse reveals that synapsis and synaptic adjustment are dependent on the size and location of the inversions and interaction between the latter. Is(1)1Icg contains insertions of the inverted repeats Is(HSR;1C5)1Icg and Is(HSR;1D)2Icg and an inverted euchromatic region. Synaptic adjustment of the D-loops by shortening of the asynapsed segments of the lateral elements belonging to the insertions occurs at the late zytogene to early pachytene stage. Synaptic adjustment of the inversion loops takes place at early to late pachytene. A delay in adjustment was found in the double heterozygotes In(1)1Icg/In(1)1Rk and In(1)1Icg/In(1)12Rk. A correspondence between the lifespan of asynapsis in inverted regions and the probability of association of XY and heteromorphic bivalents was revealed. PMID- 2265573 TI - L-cystein protects the pigment epithelium from acute sodium iodate toxicity. AB - Intravenous sodium iodate damages the retinal pigment epithelium, causing immediate loss of the electroretinogram c-wave and eventual pigmentary retinopathy. L-cystein, an agent that enhances the c-wave, has been reported to prevent the late development of pigmentary degeneration. We found in rabbits that L-cystein given 30 min before, or simultaneously with (but not 30 min after) sodium iodate also blocks the loss of the c-wave. This result occurred at doses of L-cystein lower than those needed to produce enhancement of the c-wave, suggesting that these two actions of L-cystein may be independent. The iodate blocking action of L-cystein may depend on chemical interaction. PMID- 2265574 TI - Electroretinograms and pattern visually evoked cortical potentials in central areolar choroidal dystrophy. AB - We describe three patients with central areolar choroidal dystrophy whose electroretinograms (ERGs) and pattern visually evoked cortical potentials (VECPs) confirmed their macular dysfunction. Visual fields measured by Goldmann perimetry showed central relative scotomata corresponding to a dystrophic lesion. Dark adaptation curves were slightly abnormal either in the first curve or in the second curve, depending on the visual acuity. Color vision was disturbed irregularly. Fluorescein angiography revealed a loss of the choriocapillaries, and a hyperfluorescent border outlined the dystrophic lesion. Single-flash dark adapted ERGs and scotopic ERGs were almost normal, while photopic and flicker ERGs showed slightly attenuated amplitudes. Conversely, VECPs to pattern reversal stimulation were greatly affected for both transient and steady-state stimuli. We conclude that, in central areolar choroidal dystrophy, pattern VECPs can provide more information on macular dysfunction than does the ERG. PMID- 2265575 TI - The human focal electroretinogram as a function of stimulus area. AB - Focal electroretinograms to on-off luminance modulation (2.7 Hz) of uniform fields with a different area (144-2.25 deg2) centered on the fovea were recorded in two young normal subjects. The electroretinogram responses typically consisted of an a-wave, a b-wave, a PIII component and a d-wave. The concentric reduction of the test field size caused progressive amplitude decrement of all components, while their response density increased. The spatial summation properties of the b wave differed from those of the a-wave, PIII component and d-wave so that the relative contribution of the b-wave to the electroretinogram waveform depended on the stimulus area. For a critically small field size, the electroretinogram was dominated by the PIII and d-wave components. Only these two electroretinogram components displayed a density profile that could be compared with that of cone distribution. PMID- 2265576 TI - Retinal origin of VECP delays as revealed by simultaneously recorded ERG to patterned stimuli. AB - Electroretinal and electrocortical potentials evoked by reversing checkerboards (PERG, PVECP) were simultaneously recorded in diseases of the central retina (10 patients) and in tumor-related optic nerve disorders (11 patients) exhibiting comparable P-100 delays in the PVECP. Retinal diseases showed a peak-time delay both in the PERG and in the PVECP, while optic nerve disorders revealed no delay in the PERG. Thus, simultaneous recording of PERG and PVECP may differentiate retinal from postretinal disorders of the visual system. The method also may provide information about the site of an underlying disorder in cases of visual disturbance without obvious changes of the ocular fundus. PMID- 2265577 TI - Variability of the steady-state visually evoked potential: interindividual variance and intraindividual reproducibility of spatial frequency tuning. AB - At low contrast levels there is good agreement between the psychophysical contrast sensitivity function and the tuning curve of the visually evoked potential (i.e., VEP amplitude vs spatial frequency). At high contrast, however, some researchers have found bimodal VEP tuning curves whereas others have not. We studied the VEP in 22 subjects in a short-term cross-sectional study and in 13 subjects in a longitudinal study over 8 sessions covering 28 days. Grating stimuli with 60% contrast were square-wave modulated in time (7.8 reversals/s) and space (0.06-16 cycles/degree). We found large interindividual variance in the shape of the tuning curves; about half of the subjects showed a unimodal shape, while the other half showed a bimodal one (with a 'notch' between 1 and 2 cycles/degree). These features turned out to be stable in the longitudinal study, where variability could mainly be ascribed to a multiplicative influence common to all spatial frequencies. The marked interindividual differences in the shape of the tuning curve, which seem to be intraindividually stable, may explain previous discrepancies. It is not yet clear why the notch exists in about half of our subjects. PMID- 2265578 TI - Properties of visual evoked potentials to onset of movement on a television screen. AB - In 80 subjects the dependence of movement-onset visual evoked potentials on some measures of stimulation was examined, and these responses were compared with pattern-reversal visual evoked potentials to verify the effectiveness of pattern movement application for visual evoked potential acquisition. Horizontally moving vertical gratings were generated on a television screen. The typical movement onset reactions were characterized by one marked negative peak only, with a peak time between 140 and 200 ms. In all subjects the sufficient stimulus duration for acquisition of movement-onset-related visual evoked potentials was 100 ms; in some cases it was only 20 ms. Higher velocity (5.6 degree/s) produced higher amplitudes of movement-onset visual evoked potentials than did the lower velocity (2.8 degrees/s). In 80% of subjects, the more distinct reactions were found in the leads from lateral occipital areas (in 60% from the right hemisphere), with no correlation to handedness of subjects. Unlike pattern-reversal visual evoked potentials, the movement-onset responses tended to be larger to extramacular stimulation (annular target of 5 degrees-9 degrees) than to macular stimulation (circular target of 5 degrees diameter). PMID- 2265579 TI - The effect of iodoacetic acid on the electroretinogram and oscillatory potentials in rabbits. AB - It has been shown that a single injection of iodoacetic acid selectively (but temporarily) abolishes the b-wave of the electroretinogram. We examined whether such use of this chemical further substantiate our claim that the b-wave of the electroretinogram is a composite potential resulting from the summation (or integration) of faster retinal potentials, usually referred to as the oscillatory potentials. Full-field electroretinograms were recorded from adult New Zealand rabbits before and after a single, bolus injection of 15 mg/kg of buffered iodoacetic acid. Both the 1-1000 Hz electroretinogram and the 100-1000 Hz oscillatory potentials were recorded simultaneously. The oscillatory potentials considered in this study were those normally seen on the rising phase of the b wave. Following the intravenous injection of iodoacetic acid, there was a progressive decrease in the amplitude and peak time of the b-wave. This observation also was reflected in the oscillatory potential recordings, in which the long-latency oscillatory potentials (3 and 4) progressively disappeared while oscillatory potential 2 remained. We believe that these findings further support our contention that the oscillatory potentials are major components of the b wave. PMID- 2265580 TI - Oscillatory potentials as predictors to amplitude and peak time of the photopic b wave of the human electroretinogram. AB - The oscillatory potentials are viewed by many as small oscillations of a high frequency domain that ride on the b-wave of the electroretinogram. A study of electroretinograms and oscillatory potentials performed in 25 normal subjects was undertaken to substantiate my claim that oscillatory potentials are fast retinal potentials that are integrated to form the b-wave. The prominence of the OPs on the ascending limb of the b-wave was found to be only weakly correlated (r = 0.37) to the amplitude of the oscillatory potentials (measured in the 100-1000 Hz recordings). There was, however, a high correlation (r = 0.78) between the prominence of the oscillatory potentials and their frequency domain as determined by the peak-to-peak timing. Furthermore, the peak-to-peak timing of the oscillatory potentials was highly correlated with the b-wave peak time (r = 0.86) as well as with the 'a-wave trough to b-wave peak' time (r = 0.90), while the amplitude of the oscillatory potentials was correlated to the amplitude of the b wave (r = 0.78). Interestingly, when combining the amplitude of the oscillatory potentials with the time interval between oscillatory potentials 2 and 3 and 3 and 4, a higher correlation (r = 0.88) was found with the b-wave amplitude. The latter finding would support my claim that the b-wave represents an integration (amplitude as a function of time) of the oscillatory potentials. PMID- 2265581 TI - Rod and cone contribution to adaptation processes in cat retinal ganglion cells. AB - Extracellular ganglion cell responses were recorded to investigate mechanisms of light adaptation. Monochromatic test spots (575 nm) were projected onto the receptive field center of off-center cells and superimposed on a steady blue green Ganzfeld background (Schott Filter BG 28), the strength of which was increased in steps of 0.5 log units to adapt rods. Response vs. log intensity functions were determined over a range of 7 log units of test light irradiance at each background level. At higher adaptation levels response thresholds followed the typical Weber function. Surprisingly at lower adaptation levels the sensitivity of the cell increased by about 0.7 log units, most markedly in a range of 1 log unit of moderate light adaptation when the background was changed from dark to the dimmest detectable background (10(-5) lm/m2). In the dark adapted state a small off-response of long latency (40-100 ms at 10(2) quanta.s 1.microns-2) is observed at low rod stimulating test light irradiances. A transition to a cone-dominated transient response of 2 to 5 ms duration occurred at high intensities (10(5) quanta.s-1.microns-2). At mesopic levels the two responses seem to cancel each other, rendering a delayed off-response that is probably the result of rod-cone interaction. As in psychophysics, saturation can be observed at very high background intensities (10(6) quanta.s-1 microns-2). These data suggest interactions between rods and cones that determine the sensitivity of cat retinal ganglion cells at low levels of adaptation for suprathreshold stimuli. PMID- 2265582 TI - [The instability of uniform blood-flow distribution in a microcirculatory system]. PMID- 2265583 TI - [The enzymatic and transport systems of the enterocytes during the perfusion of isolated sections of rat small intestine with different substrates in a chronic experiment]. PMID- 2265584 TI - [The effect of the vascularization of neural transplants on their structural organization]. PMID- 2265585 TI - [The Y chromosome as a marker of the systematic and historical differentiation of sympatric forms of house mice]. PMID- 2265586 TI - [The stimulation of membrane disk formation on the outer segments of rat photoreceptor cells by using para-aminobenzoic acid]. PMID- 2265587 TI - [A recombinant vaccinia virus expressing the middle preS2-S envelope protein of the hepatitis B virus. The induction of humoral and cellular immunity by the immunization of laboratory animals]. PMID- 2265588 TI - [The role of cytochrome P-450 in detoxifying the thioethynyl esters of monothiophosphoric acids]. PMID- 2265589 TI - The prevalence and self-reported consequences of cocaine use: an exploratory and descriptive analysis. AB - In this study, prevalence rates for cocaine use were estimated by sex and race, as well as for selected social role and lifestyle characteristics, including educational level, martial status, living arrangements, job type and employment status. Prevalence rates were based on an estimation procedure that made the age race-sex distributions balanced to that of the nation as a whole. Data were gathered from a multi-site probability sample of adults interviewed in 1981-1984 as part of the National Institute of Mental Health Epidemiologic Catchment Area Program (ECA) (n = 14,333). In addition to prevalence of use, rates of self reported consequences of cocaine use were generated, by level of cocaine use. Striking differences in prevalence were found by education and marital status, which remained after controlling for age of respondent. Respondents who were employed full-time had a higher prevalence of cocaine use than those who were not. Individuals residing in households at the time of interview had a 6.4% lifetime prevalence of cocaine use, vs. hospitalized respondents (22%) and incarcerated respondents (40%). Cocaine use consequence rates varied greatly across survey sites, with self-reported tolerance (28%-51%) and withdrawal sickness (8%-33%) figuring prominently among sustained daily users. PMID- 2265590 TI - Alcohol prevention among adolescents: a French experiment. AB - Under the guidance of experts, 120 secondary school students from three wine producing and three other areas of France discussed their experience with alcohol; assessed the value of materials used in primary prevention programmes; produced themselves such materials and evaluated the impact of the different approaches. From the affective and cognitive interactions resulted a noticeable change of the participants' attitude. PMID- 2265591 TI - Alcohol consumption, gender and self-reported hypertension. AB - This study examines the relationship of alcohol consumption and self-reported lifetime prevalence of hypertension among 19,284 non-institutionalized civilians in the United States. Cross-sectional data from the 1983 National Health Interview Survey, a national probability sample, were examined for each sex separately. Women who report hypertension consumed significantly less alcohol than women who did not report hypertension. Self-reported hypertensive men consumed equal or greater amounts of alcohol than self-reported normotensive men. Alcohol consumption was significantly associated with greater risk of hypertension among men, but not among women. After controlling for other risk factors significant effects for hypertension were found among males who on average consumed more than one drink/day. Beer consumption and spirits consumption above three drinks/day were significant predictors of male hypertension after adjustment for the confounding effects of other alcoholic beverage consumption and other risk factors. This study suggests that alcohol consumption by men who know that they are hypertensive is an important public health concern, with policy implications for targeting prevention efforts. PMID- 2265592 TI - Platelet monoamine oxidase activity and personality traits in alcoholics and methamphetamine dependents. AB - Personality traits of alcoholics and methamphetamine dependents were examined by Karolinska scales of personality (KSP). The two groups differed with respect to Aggression, but, they were basically same in Impulsiveness. The biological marker platelet monoamine oxidase (MAO) activity showed a significant difference between the two groups. The low platelet MAO activity in alcoholics may suggest a certain biological basis to be involved in the etiology of dependence whereas the higher platelet MAO activity observed in methamphetamine dependents may reflect the prolonged use of methamphetamine and/or treatment with neuroleptics, or some biological basis. PMID- 2265593 TI - Relationship between waiting time and retention in treatment amongst substance abusers. AB - The assumption that immediate response to substance abusers' pleas for help increases the likelihood of retention in treatment is tested in a substance abuse facility in the Home Counties which offers a range of treatment options excluding prescription of narcotics substitutes. It has shorter waiting times between referral and first appointments and higher rates of initial attendance than the local general psychiatric clinics. Patients seen within 7 days continue to attend for no longer than those who have to wait longer. Those who continue longer are more likely to be referred by their G.P., are more likely to have alcohol or alcohol and other drug related problems and are less likely to seek or need immediate inpatient admission. PMID- 2265594 TI - Alcohol, AIDS risks and sex industry clients: results from a Scottish study. AB - During 1988 and 1989 self-reported data were obtained from 206 males and three females who had paid for physical sexual services. Respondents were contacted by "snowballing", mainly with the assistance of sex workers. The study group reported that both alcohol and illicit drug use were commonplace during their contact with prostitutes. No general association between alcohol and drug use and 'risky sex' was evident. Even so amongst males who had anal sex with males alcohol consumption was inversely related to condom use. PMID- 2265595 TI - White matter damage in preterm newborns--an epidemiologic perspective. AB - Prior to 1980, white matter abnormalities of the preterm newborn were known exclusively as pathological entities, but now cranial ultrasonography can image white matter abnormalities in life. Ultrasonographic white matter echodensities and echolucencies in low birthweight babies predict later handicap (especially cerebral palsy) more accurately than any other antecedent. With the increased availability of high resolution cranial ultrasonography and the improved skill in obtaining and reading cranial ultrasonograms, rapid gains can be expected in our understanding of white matter disorders. These advances are likely to be made in the diagnosis and classification of white matter disorders and in their epidemiologic and prognostic features, topics explored in this review. PMID- 2265596 TI - Effects of maternal cigarette smoking on ultrasonic measurements of fetal growth and on Doppler flow velocity waveforms. AB - Serial ultrasound biometry and Doppler flow velocity waveform analysis were used to measure the effects of maternal smoking in a prospective study of 535 pregnancies. Smoking was associated with significant reductions in maternal weight gain, birthweights and placental weights. Decreased fetal biparietal diameter measurements were observed in pregnancies of smoking women; this effect was maximal at 24 weeks' gestation, was restricted to male fetuses and was not associated with altered head circumferences after birth. Umbilical artery and uteroplacental systolic/diastolic ratios were similar in pregnancies of smoking and non-smoking women, indicating that the effects of smoking on placental vascular resistance are periodic rather than continuous. The findings of this study confirm the need for studies of fetal growth to include prenatal measurements obtained by high resolution ultrasound imaging, rather than relying on findings obtainable by examination of the infant after birth. PMID- 2265597 TI - Normal fetal growth evaluated by longitudinal ultrasound examinations. AB - Fetal weight estimation was evaluated using the equations of Warsof, Shepard and Hadlock in 192 patients, less than 3 days before delivery. Warsof's and Hadlock's equations resulted in significantly better weight estimates compared to Shepard's equation. No systematic error was found below 2500 g by use of Warsof's equation, whereas Shepard's and Hadlocks's equations resulted in significant over estimation in the low weight group. In a study of 5 fetuses, of 27-38 weeks gestational age, the intra-observer variation was calculated to 4.6%, whereas the coefficient of variation among observer means was 2.9%. The mixed intra- and inter-observer coefficient of variation was 6.5%. Thirty-five low-risk, uncomplicated pregnancies with reliable last menstrual dates were investigated longitudinally with ultrasound measurements of fetal weight. Population growth curves of fetal weight, fetal femur length, abdominal circumference and biparietal diameter were constructed by weighted polynomial regression. After 27 weeks of gestational age the weight growth curve showed only insignificant non linearity. Compared to a Danish growth curve based on birth weights, significant higher mean weight was found, especially before 31 weeks of gestational age. The 10th and 90th percentiles for the individual percentage deviation change was +/- 4.4% per 28 days. PMID- 2265598 TI - Development of the human renal inner medullary interstitial cells. AB - Two cell types were identified in the inner medulla and papilla of four fetal kidneys of 16 1/7-, 17 3/7-, 21 1/7- and 25 5/7-week-old (menstrual): undifferentiated mesenchymal cells and some highly differentiated cells which contained some lipid granules, lysosomes, smooth and rough endoplasmic reticulum. The structure of these cells resembled the two cell types which were observed in the adult tissue. PMID- 2265599 TI - Combined impedance and inductance for the detection of apnoea of prematurity. AB - To compare two methods of detecting central apnoea, 27 preterm infants (median birth weight 1.14 kg, gestation 29 weeks) were studied on 89 occasions, using combined thoracic impedance and abdominal respiratory inductive plethysmography. During 353 h recording time, 946 apnoeic episodes were noted. In 651 of these, there was agreement between impedance and inductance traces, but apnoea appeared longer in 106 episodes on impedance, and in 189 on inductance. If a single system had been used 27 would have been missed by inductance and 112 by impedance (P less than 0.05). Failure of impedance monitoring was mainly due to technical reasons, especially cardiac artefact, and to movement. The use of a dual system of impedance and inductance offers improved detection of central apnoea, particularly for research purposes. PMID- 2265600 TI - Language development of very low birth weight infants and fullterm controls at 12 months of age. AB - Twenty-eight very low birth weight (VLBW) and 32 full term infants were prospectively assessed at one year of age for hearing, language development and neurological status. The prevalence of conductive hearing deficits was the same in both groups. Language scores in VLBW infants were significantly lower than in fullterm controls and 39% had significant language delays. VLBW infants exhibited a shorter attention span and were less likely to understand simple questions, to recognize objects or body parts when named, to initiate speech-gesture games, to follow simple commands and to imitate or use words consistently. Language quotients were directly associated with gestational age and five minute Apgar scores and inversely associated with severity of intraventricular hemorrhage, bronchopulmonary dysplasia and length of hospital stay. VLBW small for gestational age infants exhibited more advanced language skills than VLBW appropriate for gestational age infants. Language delays were more prevalent among, but not limited to, infants with mild to moderate neurological abnormalities. The influence of prematurity and VLBW on language development is complex and multifactorial and research is continuing to determine the predictive validity and long term significance of the early language delays described in this study. PMID- 2265601 TI - [Prostaglandins E1 and psychopathogeny of schizophrenia]. AB - The authors assess the results of several studies, fundamental or clinical with therapeutic tests, to demonstrate a possible role of prostaglandins--specially of a possible lack of PGE1--in the pathogeny of certain forms of schizophrenia. The heterogeneousness of the results leads one to think there's heterogeneousness of the illness. Meanwhile, in certain cases, the contribution of a direct precursor of PGE1 the GLA, has given possible noticeable clinical results, mainly with deficiency symptoms. PMID- 2265602 TI - [Analysis of the relations between polysomnographic data and subjective evaluation of sleep in a group of normal subjects]. AB - The aim of the present study was to analyse the relationships between polysomnographic variables and the subjective evaluation of sleep quality in a sample of healthy subjects. Thirty one healthy subjects (7 women, 24 men) aged 16 to 74 (mean = 33.8; standard-deviation = 15.6) were included in the study. After one accommodation night, sleep was recorded during three consecutive nights in the sleep laboratory. Subjective evaluation of sleep quality was assessed by a questionnaire including quantitative aspects as well as qualitative aspects of sleep. The data of the third night are analysed here. Two factor analyses were performed on the sleep questionnaire. Two factors were extracted; they were named "depth" and "rest". Using a stepwise multiple regression analysis, these two indices of sleep quality were tested for explanation by 24 polygraphic variables. The "depth" factor was revealed positively related to the first awakening latency, and negatively to sleep onset latency, Rapid Eye Movement latency and the number of awakenings. The "rest" factor was shown to be positively related to stage 1 duration and sleep onset latency, and negatively to stage 4 duration and the number of awakenings. Some of these relationships have already been described. Others seem surprising and may seem questionable. These results raise the question of the relations between objective measures of sleep, the polygraphic variables, and the subjective process of perceiving and evaluating sleep. PMID- 2265603 TI - [Amineptin dependence. Detection of patients at risk. Report of 8 cases]. AB - The authors relate eight cases of amineptine dependency collected between 1980 and 1988 in 7 women and 1 man treated in the CHU of Besancon (France). The pharmacodependency appeared to be limited mainly to an abuse and a psychic dependence, i.e. a compulsive need to use the drug on a periodic (two cases) or continuing (six cases) basis in order to experience its psychomotor stimulant like effect. The used dosages ranged between 1,000 and 2,500 mg per day. The daily dose was divided into little doses, every hour for example. The induction modality was progressive during weeks or months and a stable dose period was then encountered. In one patient only, we observed a progressive increase of the dose without stabilisation of the dose. The withdrawal of amineptine was obtained without problem except in 2 cases where we observed clinical manifestations of anxiety, psychomotor agitation or bulimia during one day. Four years after the beginning, amineptine dependence was still present in 2 patients. In 4 patients we obtained an interruption of the amineptine pharmacodependency for one to three years. We did not see again the two remaining patients. In two cases, the main diagnosis, according to DSM III, was a major personality disorder (borderline). In the six other cases the diagnosis was a bipolar affective disorder (including four cases with only hypomanic episodes only). In these six patients the main characteristic of their affective illness was the association with other psychiatric disorders, especially personality disorders, such as borderline personality in one case and atypical personality with uncontrolled behavior as the main feature, in the 5 other patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265604 TI - [Suicide risk in clinical trials of antidepressive agents with a placebo group]. PMID- 2265605 TI - Delineation of antigen contact residues on an MHC class II molecule. AB - This report describes a detailed mutational analysis of a major histocompatibility complex class II molecule--the alpha chain of the Ak complex. Each residue from 50-79 was replaced by an alanine, and the effects on recognition of Ak by panels of antibodies and T cells determined. The results provide the strongest existing experimental evidence that the antigen binding site on a class II molecule can be modelled on the crystal structure of a class I molecule. The data have also permitted the delineation of residues that actually contact antigenic peptides. PMID- 2265606 TI - Intermediates in influenza induced membrane fusion. AB - Our results show that the mechanism by which influenza virus fuses with target membranes involves sequential complex changes in the hemagglutinin (HA, the viral fusion protein) and in the contact site between virus and target membrane. To render individual steps amenable to study, we worked at 0 degree C which decreased the rate of fusion and increased the efficiency. The mechanism of fusion at 0 degree C and 37 degrees C was similar. The process began with a conformational change in HA which exposed the fusion peptides but did not lead to dissociation of the tops of the ectodomain of the trimer. The change in the protein led to immediate hydrophobic attachment of the virus to the target liposomes. Attachment was followed by a lag period (4-8 min at 0 degree C, 0.6-2 s at 37 degrees C) during which rearrangements occurred in the site of membrane contact between the virus and liposome. After a further series of changes the final bilayer merger took place. This final fusion event was not pH dependent. At 0 degree C efficient fusion occurred without dissociation of the top domains of the HA trimer, suggesting that a transient conformation of HA is responsible for fusion at physiological temperatures. The observations lead to a revised model for HA mediated fusion. PMID- 2265607 TI - Elucidation of amidating reaction mechanism by frog amidating enzyme, peptidylglycine alpha-hydroxylating monooxygenase, expressed in insect cell culture. AB - A frog 'peptidylglycine alpha-amidating monooxygenase (PAM, EC 1.14.17.3)' was expressed in cultured insect cells by using the baculovirus expression vector system. The enzyme, recovered in the culture medium, was purified to homogeneity. Its apparent molecular mass (43 kd), estimated by both SDS-PAGE and molecular sieving, was higher than the value (39 kd) for the 'PAM' (AE-I) purified from frog skin. N-terminal sequence analysis indicated that cleavage of signal sequence had occurred but the propeptide still remained at the N terminus. The glycine-extended model peptide X-Gly (mean = Ala-Ile-Gly-Val-Gly-Ala-Pro) was used as substrate for the purified enzyme. The reaction product formed at pH 5.4 was isolated and characterized by amino acid sequence analysis, FAB-MASS and 1H NMR. It was shown that the purified enzyme had converted the model peptide to the C-terminal alpha-hydroxyglycine-extended peptide [X-Gly(OH)] instead of the amidated product (X-NH2), indicating that the enzyme widely known as 'PAM' should be called 'peptidylglycine alpha-hydroxylating monooxygenase'. A novel enzyme, present in the insect cell culture medium and separable from the expressed monooxygenase, could convert the alpha-hydroxyglycine-extended peptide to the amidated product at physiological pH values. It is concluded that the alpha amidation of glycine-extended peptides is a two-step process catalyzed by the monooxygenase and the novel enzyme. PMID- 2265608 TI - The molecular genetics of the bithorax complex of Drosophila: cis-regulation in the Abdominal-B domain. AB - In Drosophila the Abdominal-B (Abd-B) domain of the bithorax complex (BX-C) spans over 100 kb and is responsible for specifying the identities of adult abdominal segments five (A5) to nine (A9), inclusive, and correspondingly, neuromeres 10-14 of the embryonic central nervous system. The domain consists of a region coding for two proteins, ABD-BI (54 kd) and ABD-BII (36 kd) and cis-regulatory regions extending from infra-abdominal-5 (iab-5) to iab-9, inclusive. We have used a monoclonal anti-ABD-B antibody to infer that mutants in iab-8 eliminate the expression of ABD-BI in neuromeres 10-13, inclusive, and that mutants in iab-9 eliminate expression of ABD-BII in neuromere 14. ABD-B expression is also analyzed in homozygotes for (i) loss-of-function mutants involving the iab-5, iab 6 and iab-7 regions, (ii) gain-of-function mutants Miscadastral pigmentation (Mcp) and Superabdominal (Sab), and (iii) a trans-regulator, Polycomb (Pc). ABD-B expression along the antero-posterior axis is colinear with the chromosomal order of the cis-regulatory regions. The behavior of rearrangement-associated iab-6 and iab-7 mutants suggests that the enhancer-like region, iab-5, and possibly also iab-6, may be shared between the abd-A and Abd-B domains. Such sharing is proposed as a factor that tends to keep gene complexes intact during evolution. PMID- 2265609 TI - A precursor protein partly translocated into yeast mitochondria is bound to a 70 kd mitochondrial stress protein. AB - We have probed the environment of a precursor protein stuck in mitochondrial import sites using cleavable bifunctional crosslinking reagents. The stuck precursor was crosslinked to a 70 kd protein which, by immunological techniques, was shown to be a matrix protein. The protein was purified to homogeneity by ATP Sepharose chromatography and partially sequenced. Fourteen of its 15 N-terminal amino acids were identical to residues 24-38 of the protein encoded by the nuclear gene SSC1, which had been proposed to encode a dnaK-like 70 kd mitochondrial stress protein. Our data imply that this mitochondrial hsp70 is made with a cleavable matrix-targeting sequence composed of 23 residues. The complex containing stuck precursor, mitochondrial hsp70, and ISP42 could be solubilized from mitochondria by the non-ionic detergent Triton X-100 even without crosslinking, suggesting tight association of these three components. As the stuck precursor is arrested at an early stage of translocation, mitochondrial hsp70 may initiate the events that lead to refolding of imported precursors in the matrix space. PMID- 2265610 TI - The CHL 1 (CTF 1) gene product of Saccharomyces cerevisiae is important for chromosome transmission and normal cell cycle progression in G2/M. AB - We have analyzed the CTF1 gene, identified in a screen for mutants with decreased chromosome transmission fidelity and shown to correspond to the previously identified chl1 mutation. Chl1 null mutants exhibited a 200-fold increase in the rate of chromosome III missegregation per cell division, and near wild-type rates of marker homozygosis on this chromosome by mitotic recombination. Analysis of the segregation of a marker chromosome indicated that sister chromatid loss (1:0 segregation) and sister chromatid non-disjunction (2:0 segregation) contributed equally to chromosome missegregation. A genomic clone of CHL1 was isolated and used to map its physical position on chromosome XVI. Nucleotide sequence analysis of CHL1 revealed a 2.6 kb open reading frame with a 99 kd predicted protein sequence that contained two PEST sequences and was 23% identical to the coding region of a nucleotide excision repair gene, RAD3. Domains of homology between these two predicted protein sequences included a helix-turn-helix motif and an ATP binding site containing a helicase consensus. Mutants lacking the CHL1 gene product are viable and display two striking, and perhaps interrelated, phenotypes: extreme chromosome instability and a delay in cell cycle progression in G2/M. This delay is independent of the cell cycle checkpoint that requires the function of the RAD9 gene. PMID- 2265611 TI - Growth rate dependence of transfer RNA abundance in Escherichia coli. AB - We have tested the predictions of a model that accounts for the codon preferences of bacteria in terms of a growth maximization strategy. According to this model the tRNA species cognate to minor and major codons should be regulated differently under different growth conditions: the isoacceptors cognate to major codons should increase at fast growth rates while those cognate to minor codons should decrease at fast growth rates. We have used a quantitative Northern blotting technique to measure the abundance of the methionine and the leucine isoacceptor families over growth rates ranging from 0.5 to 2.1 doublings per hour. Five tRNA species that are cognate to major codons (tRNA(eMet), tRNA(1fMet), tRNA(2fMet), tRNA(1Leu) and tRNA(3Leu) increase both as a relative fraction of total tRNA and in absolute concentration with increasing growth rates. Three tRNA species that are cognate to minor codons (tRNA(2Leu), tRNA(4Leu) and tRNA(5Leu) decrease as a relative fraction of total RNA and in absolute concentration with increasing growth rates. These data suggest that the abundances of groups of tRNA species are regulated in different ways, and that they are not regulated simply according to isoacceptor specificity. In particular, the data support the growth optimization model for codon bias. PMID- 2265612 TI - Molecular cloning and expression of the murine interleukin-5 receptor. AB - Murine interleukin-5 (IL-5) is known to play an essential role in Ig production of B cells and proliferation and differentiation of eosinophils. Here, we have isolated cDNA clones encoding a murine IL-5 receptor by expression screening of a library prepared from a murine IL-5 dependent early B cell line. A cDNA library was expressed in COS7 cells and screened by panning with the use of anti-IL-5 receptor monoclonal antibodies. The deduced amino acid sequence analysis demonstrates that the receptor is a glycoprotein of 415 amino acids (Mr 45,284), including an N-terminal hydrophobic region (17 amino acids), a glycosylated extracellular domain (322 amino acids), a single transmembrane segment (22 amino acids) and a cytoplasmic tail (54 amino acids). COS7 cells transfected with the cDNA expressed a 60 kd protein that bound IL-5 with a single class of affinity (KD = 2-10 nM). FDC-P1 cells transfected with the cDNA for murine IL-5 receptor showed the expression of IL-5 binding sites with both low (KD = 6 nM) and high affinity (KD = 30 pM) and acquired responsiveness to IL-5 for proliferation, although parental FDC-P1 cells did not show any detectable IL-5 binding. In addition, several cDNA clones encoding soluble forms of the IL-5 receptor were isolated. Northern blot analysis showed that two species of mRNAs (5.0 kb and 5.8 kb) were detected in cell lines that display binding sites for murine IL-5. Homology search for the amino acid sequence of the IL-5 receptor reveals that the IL-5 receptor contains a common motif of a cytokine receptor family that is recently identified. PMID- 2265613 TI - Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. AB - The promoter region of the human C-reactive protein (CRP) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans activating transcription from the wild-type CRP promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression. PMID- 2265614 TI - Light-induced switch in barley psbD-psbC promoter utilization: a novel mechanism regulating chloroplast gene expression. AB - The synthesis of reaction center protein D2 and mRNAs which encode this protein are differentially maintained at high levels in mature barley chloroplasts. To understand the differential maintenance of psbD mRNA abundance, we have studied the transcription and the RNAs produced from the psbD-psbC operon in plastids of light and dark-grown barley seedlings. Ten psbD-psbC RNAs synthesized in dark grown barley share four different 5'-ends, two of which arise by transcription initiation, and one of which is generated by 5'-processing of longer psbD-psbC transcripts. Illumination of dark-grown barley causes the decline of these ten transcripts, and the accumulation of two different psbD-psbC RNAs. Capping assays, in vitro transcription and RNA processing experiments and treatment of plants with tagetitoxin (a selective inhibitor of chloroplast transcription), indicate that the light-induced transcripts arise by transcription initiation. Run-on transcription and RNA quantitation experiments provide evidence that both light-induced transcription and RNA stability play roles in the accumulation of the light-induced RNAs. These data document a novel mechanism for regulating plastid gene expression involving a light-induced switch in psbD-psbC promoter utilization. PMID- 2265615 TI - Identification of essential elements in U14 RNA of Saccharomyces cerevisiae. AB - The U14 RNA of Saccharomyces cerevisiae is a small nucleolar RNA (snoRNA) required for normal production of 18S rRNA. Depletion of U14 results in impaired processing of pre-rRNA, deficiency in 18S-containing intermediates and marked under-accumulation of mature 18S RNA. The present report describes results of functional mapping of U14, by a variety of mutagenic approaches. Special attention was directed at assessing the importance of sequence elements conserved between yeast and mouse U14 as well as other snoRNA species. Functionality was assessed in a test strain containing a galactose dependent U14 gene. The results show portions of three U14 conserved regions to be required for U14 accumulation or function. These regions include bases in: (i) the 5'-proximal box C region, (ii) the 3'-distal box D region, and (iii) a 13 base domain complementary to 18S rRNA. Point and multi-base substitution mutations in the snoRNA conserved box C and box D regions prevent U14 accumulation. Mutations in the essential 18S related domain do not effect U14 levels, but do disrupt synthesis of 18S RNA, indicating that this region is required for function. Taken together, the results suggest that the box C and box D regions influence U14 expression or stability and that U14 function might involve direct interaction with 18S RNA. PMID- 2265616 TI - Significance of the third tRNA binding site, the E site, on E. coli ribosomes for the accuracy of translation: an occupied E site prevents the binding of non cognate aminoacyl-tRNA to the A site. AB - The E site (exit site for deacyl-tRNA) has been shown to be allosterically linked to the A site (aminoacyl-tRNA binding site), in that occupation of the E site reduces the affinity of the A site, and vice versa, whereas the intervening peptidyl-tRNA binding site (P site) keeps its high affinity. Here the question is analysed of whether or not the low affinity state of the A site caused by an occupied E site is of importance for the ribosomal accuracy of the aminoacyl-tRNA selection. In a poly(U) dependent system with high accuracy in poly(Phe) synthesis, the acceptance of the cognate ternary complex Phe-tRNA--EF-Tu--GTP (which has the correct anticodon with respect to the codon at the A site) was compared with the competing acceptance of ternary complexes with near-cognate Leu tRNA(Leu) (which has a similar anticodon) or non-cognate Asp-tRNA(Asp) (which has a dissimilar anticodon), by monitoring the formation of AcPhePhe, AcPheLeu or AcPheAsp, respectively. Cognate (but not near-cognate) occupation of the E site reduced synthesis of the 'wrong' dipeptide AcPheLeu only marginally relative to that of the cognate AcPhe2, whereas the formation of AcPheAsp was decreased as much as 14-fold, thereby reducing it to the background level. It follows that the allosteric interplay between E and A sites, i.e. the low affinity of the A site induced by the occupation of the E site, excludes the interference of non-cognate complexes in the decoding process and thus reduces the number of aminoacyl-tRNA species competing for A site binding by an order of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265617 TI - UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin conjugating enzymes involved in protein degradation. AB - The covalent attachment of ubiquitin to cellular proteins is catalyzed by members of a family of ubiquitin-conjugating enzymes. These enzymes participate in a variety of cellular processes, including selective protein degradation, DNA repair, cell cycle control, and sporulation. In the yeast Saccharomyces cerevisiae, two closely related ubiquitin-conjugating enzymes, UBC4 and UBC5, have recently been shown to mediate the selective degradation of short-lived and abnormal proteins. We have now identified a third distinct member of this class of ubiquitin-conjugating enzymes, UBC1. UBC1, UBC4 and UBC5 are functionally overlapping and constitute an enzyme family essential for cell growth and viability. All three mediate selective protein degradation, however, UBC1 appears to function primarily in the early stages of growth after germination of spores. ubc1 mutants generated by gene disruption display only a moderate slow growth phenotype, but are markedly impaired in growth following germination. Moreover, yeast carrying the ubc1ubc4 double mutation are viable as mitotic cells, however, these cells fail to survive after undergoing sporulation and germination. This specific requirement for UBC1 after a state of quiescence suggests that degradation of certain proteins may be crucial at this transition point in the yeast life cycle. PMID- 2265618 TI - Direct visualization of supercoiled DNA molecules in solution. AB - The shape of supercoiled DNA molecules in solution is directly visualized by cryo electron microscopy of vitrified samples. We observe that: (i) supercoiled DNA molecules in solution adopt an interwound rather than a toroidal form, (ii) the diameter of the interwound superhelix changes from about 12 nm to 4 nm upon addition of magnesium salt to the solution and (iii) the partition of the linking deficit between twist and writhe can be quantitatively determined for individual molecules. PMID- 2265621 TI - Atraumatic introduction of an intravascular sheath. AB - A new sheath comprising three circular plastic tubes which slide concentrically over each other is described. Since there is no step in the direction of introduction, an atraumatic vessel-puncture is possible. PMID- 2265619 TI - Cloning and expression in Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces cerevisiae; a homologue to the bacterial alkA gene. AB - An alkylation repair deficient mutant of Escherichia coli (tag ada), lacking DNA glycosylase activity for removal of alkylated bases, was transformed by a genomic yeast DNA library and clones selected which survived plating on medium containing the alkylating agent methylmethane sulphonate. Three distinct yeast clones were identified which were able to suppress the alkylation sensitive phenotype of the bacterial mutant. Restriction enzyme analysis revealed common DNA fragments present in all three clones spanning 2 kb of yeast DNA. DNA from this region was sequenced and analysed for possible translation of polypeptides with any homology to either the Tag or the AlkA DNA glycosylases of E. coli. One open reading frame of 296 amino acids was identified encoding a putative protein with significant homology to AlkA. DNA containing the open reading frame was subcloned in E. coli expression vectors and cell extracts assayed for alkylbase DNA glycosylase activity. It appeared that such activity was expressed at levels sufficiently high for enzyme purification. The molecular weight of the purified protein was determined by SDS-PAGE to be 35,000 daltons, in good agreement with the 34,340 value calculated from the sequence. The yeast enzyme was able to excise 7 methylguanine as well as 3-methyladenine from dimethyl sulphate treated DNA, confirming the related nature of this enzyme to the AlkA DNA glycosylase from E. coli. PMID- 2265622 TI - Diagnostic aspiration of abdominal fluid in patients with acute abdomen. AB - Twenty-two patients with acute abdominal symptoms were studied by abdominal sonography and by sonographically guided aspiration of intraperitoneal fluid. The colour of the fluid was found to be diagnostically valuable: a green colour indicated gallbladder perforation, a yellow colour was found in a variety of infectious diseases, a red colour in haemorrhagic pancreatitis or haemorrhage. Aspirating fluid from the peritoneal cavity under ultrasound guidance in connection with any routine ultrasound examination is a valuable and easy method for studying patients with symptoms of acute abdomen. PMID- 2265620 TI - Saccharomyces cerevisiae 3-methyladenine DNA glycosylase has homology to the AlkA glycosylase of E. coli and is induced in response to DNA alkylation damage. AB - We previously cloned a DNA fragment from Saccharomyces cerevisiae that suppressed the alkylation sensitivity of Escherichia coli glycosylase deficient mutants and we showed that it apparently contained a gene for 3-methyl-adenine DNA glycosylase (MAG). Here we establish the identity of the MAG gene by sequence analysis and describe its in vivo function and expression in yeast cells. The MAG DNA glycosylase specifically protects yeast cells against the killing effects of alkylating agents. It does not protect cells against mutation; indeed, it appears to generate mutations which presumably result from those apurinic sites produced by the glycosylase that escape further repair. The MAG gene, which we mapped to chromosome V, is not allelic with any of the RAD genes and appears to be allelic to the unmapped MMS-5 gene. From its sequence the MAG glycosylase is predicted to contain 296 amino acids and have a molecular weight of 34,293 daltons. A 137 amino acid stretch of the MAG glycosylase displays 27.0% identity and 63.5% similarity with the E. coli AlkA glycosylase. Transcription of the MAG gene, like that of the E. coli alkA gene, is greatly increased when yeast cells are exposed to relatively non-toxic levels of alkylating agents. PMID- 2265623 TI - Endoscopic ultrasonographic findings in benign and malignant diseases of the stomach. AB - Endoscopic ultrasonographic (EUS) imaging was performed to examine the depth, extent and tissue character of gastric lesions in nine patients. Two patients with linitis plastica had endoscopically normal gastric mucosa, but a thickened gastric wall showing loss of normal layer structure on examination with EUS. In four patients the internal structure of gastric polyps could be imaged, showing the relationship to the gastric wall layers. EUS demonstrated the depth of gastric ulcers in three patients. Abnormalities in the echogenicity of the gastric wall adjacent to the ulcers were observed. EUS provides a three dimensional endoscopic and ultrasonographic picture of the gastric mucosal surface and underlying wall, providing structural information not otherwise obtainable without examining the resected tissue. PMID- 2265624 TI - Radiologic diagnosis of renal colic: the role of plain films, excretory urography and sonography. AB - The accuracy of plain films, excretory urography and ultrasound for the clinical work-up of renal colic for detecting urinary calculi was evaluated prospectively in 49 patients. Excretory urography was the most sensitive and specific test. Plain films and sonography each had a sensitivity of approximately 60%, but combined yielded a sensitivity of 80%; specificity did not improve. A diagnostic algorithm where sonography was performed first followed by an excretory urography in case of a negative sonography was highly sensitive (93%) and rather specific (79%). This algorithm appears also to have a good cost-benefit rate. PMID- 2265625 TI - Herniography in 79 patients with unexplained pain in the groin: a retrospective study. AB - To assess the safety and accuracy of herniography for the diagnosis of inguinal hernia in young military men with unexplained pain in the groin, a retrospective study in 79 patients with unexplained pain in the groin who underwent a herniography is presented. Nineteen patients (24%) showed a positive herniogram which was confirmed in 15 out of 16 patients who subsequently underwent surgery. All 60 (76%) patients with a negative herniography were followed-up. An inguinal hernia was subsequently found at surgery in two patients out of eight who were operated on later. In our series no serious complications occurred. Herniography has been shown to be a safe and reliable method to demonstrate or exclude an inguinal hernia in young military men with unexplained pain in the groin. The differential diagnosis in this specific patient group is discussed. PMID- 2265626 TI - Radiologic appearances of Brunner's gland adenoma: a case report. PMID- 2265628 TI - Magnetization-prepared rapid gradient echo (MP-RAGE) magnetic resonance imaging of Morgagni's hernia. PMID- 2265627 TI - Determination of liver volume in vivo in rats using MRI. AB - Accurate estimation of the liver volume may be important for the diagnosis of several pathological processes in patients and for the study of new therapies in experimental oncology. Although sonography and computed tomography (CT) have been used for this purpose in patients, the lack of spatial resolution and tissue differentiation is a source of measurement errors which, at present, makes it impossible to accept sonography and CT widely for the determination of the liver volume. In the present study, the liver volumes of seven rats were measured by magnetic resonance imaging (MRI) and an automated image analysis system before and after the animals were killed. Volume computation was carried out by adding up the individual volumes in the sequential MR sections. Adequate MR images with high contrast between the liver and surrounding structures were obtained with spin echo pulse sequence and retarded phase encoding while no contrast material was used. The mean volumes of the livers measured by MR in vivo and in cadavers were 11.91 +/- 0.40 and 11.92 +/- 0.45 ml, respectively. When compared with the actual liver volumes measured in vitro after resection, the errors of determinations in vivo and in cadavers were as small as 3.1 and 2.1%, respectively. These data indicate that MR imaging is an accurate means to determine the liver volume in vivo and that it may be potentially useful to measure small intrahepatic lesions in patients. PMID- 2265629 TI - Method of measurement of the cardio-thoracic ratio. PMID- 2265630 TI - Interobserver variation in the detection of pulmonary venous hypertension in chest radiographs. AB - A total of 171 sets of chest radiographs chosen randomly were reviewed independently by two residents in their second year of training, and two experienced radiologists. The degree of interobserver agreement in an overall assessment of pulmonary venous hypertension and in the assessment of five signs, indicative of pulmonary venous hypertension was determined by kappa statistics. The average level of agreement was moderate (0.51-0.56) for the overall assessment and the signs of perivascular clouding, perihilar haze and pleural effusion, and poorer (0.31-0.38) for flow shift and Kerley lines. In the overall assessment agreement between experienced radiologists was slightly better (0.63) than average. Multiple reader interpretation is recommended for the assessment of low-grade pulmonary venous hypertension. PMID- 2265631 TI - MR findings in thyroglossal duct cysts: report of two cases. AB - Two patients with thyroglossal duct cysts have been studied with CT and MR. The typical CT feature of these cystic upper-neck lesions are depicted in literature, conversely MR findings are not well known. The homogeneous high intensity on T1 weighted images, higher than simple cyst or fluid, is the most typical feature of the thyroglossal cyst. PMID- 2265632 TI - Spinal epidural hydatid cyst: radiological and ultrasonographical workup of a case. PMID- 2265633 TI - Cystic hygroma of the breast. PMID- 2265634 TI - Subsequent bilateral occurrence of fibrous breast tumors; a case report. PMID- 2265635 TI - Calcinosis circumscripta: report of a case. PMID- 2265636 TI - Infarction of the cervical spinal cord after exertion: a case report. PMID- 2265637 TI - Elimination of Gd-DTPA by means of hemodialysis. AB - After intravenous administration of Gd-DTPA (0.1 mmol/kg) hemodialysis was performed five times within 6 days in a patient with endstage renal failure. During the fifth hemodialysis a blood sample of 5 ml was withdrawn and Gd concentration was measured in plasma at 342.247 nm using the method of Inductively Coupled Plasma Atomic Emission Spectrometry. Gd-concentration measured in venous and arterial blood was 6 x 10(-6) mol/liter, corresponding to 1.5% of the dose administered. If these data can be confirmed in more patients with endstage renal failure, this is the proof of effective hemodialysis of Gd DTPA in a clinical setting. PMID- 2265638 TI - Successful treatment of disseminated hydatid disease using albendazole monitored by CT. PMID- 2265639 TI - Risk stratification and prognosis of patients with recent onset angina. AB - We prospectively assessed coronary artery disease and natural history in a series of 104 patients (99 males, mean age 52 +/- 8 years) admitted with recent onset angina (defined as a history of angina of less than 1 month duration). Coronary angiography showed one-vessel disease in 31, two-vessel disease in 22 and three vessel disease in 14; 37 patients had normal coronary arteries. After a mean follow-up of 36 (range 1 to 52) months, one patient died, 13 sustained a myocardial infarction and 21 underwent surgery. The univariate analysis showed four of 12 clinical features derived from clinical history and data from CCU (exertional angina (P less than 0.001), and recurrence of angina (P less than 0.05)) to be associated with the presence of coronary artery disease. These clinical features were termed clinical risk characteristics. Three-year probability of medical events (death or acute myocardial infarction) for patients with 0-1 clinical risk characteristics was 0 and that of combined events (need for revascularization with or without a preceding medical event) 0.11, whereas patients with 2 or more risk characteristics had probabilities of 0.27 and 0.49, respectively. Multivariate analysis identified the number of clinical risk characteristics as the only independent predictor of medical events (P less than 0.002) and a positive thallium stress test (P less than 0.0001), the number of clinical risk characteristics (P less than 0.002) and the number of involved arteries (P less than 0.002), as independent predictors of combined events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265640 TI - Intravenous streptokinase in acute myocardial infarction (I.S.A.M.): assessment of left ventricular function 1 and 7 months after infarction by radionuclide ventriculography. AB - I.S.A.M. was a prospective, placebo-controlled, double-blind multicentre trial of high-dose short-term intravenous streptokinase in acute myocardial infarction (AMI) within 6 h of the onset of symptoms. Determination of left ventricular ejection fraction (LVEF) by radionuclide ventriculography was performed 1 and 7 months after AMI in a subset of 192 patients at rest and, in 140 of them, also during exercise. Regional myocardial function was analysed in all 145 patients with neither a history of a previous myocardial infarction nor revascularization procedures or reinfarction within the 7-month follow-up period. One month after AMI, mean LVEF was higher in the streptokinase group in patients with anterior AMI (50 +/- 15% vs 42 +/- 16%, P = 0.013). This difference was more marked in the subgroup treated within 3 h (53 +/- 14% vs 42 +/- 15%, P = 0.004), whereas patients treated 3-6 h after the onset of symptoms did not differ from respective controls (41 +/- 16% vs 41 +/- 18%). In patients with inferior AMI, the difference in mean LVEF was small (57 +/- 11% vs 55 +/- 12%, P = 0.47). After anterior AMI benefit due to streptokinase therapy was preserved up to 7 months (52 +/- 14% vs 44 +/- 17%, P = 0.013). During exercise, the increase of mean LVEF was greater in the streptokinase group at both dates, especially 7 months after AMI (4.1 +/- 6.1% vs 1.2 +/- 6.3%, P = 0.015). In streptokinase-treated patients with anterior AMI, regional LVEF at rest was higher at both dates compared with controls, within the infarct zone as well as in remote myocardium. No treatment control differences were demonstrable in patients with inferior AMI. During exercise, regional contractile reserve was better in the streptokinase group within the infarct zone as well as in remote myocardium, irrespective of the site of infarction. Thus, intravenous streptokinase within 3 h after the onset of AMI preserves global left ventricular function in anterior AMI over a period of at least 7 months. Intravenous streptokinase improves regional myocardial function within the infarct zone as well as in remote areas. In inferior AMI investigation solely at rest may underestimate the benefit of streptokinase therapy. PMID- 2265641 TI - Effects of mental and physical stress on central haemodynamics and cardiac sympathetic nerve activity during QT interval-sensing rate-responsive and fixed rate ventricular inhibited pacing. AB - The effects of mental stress and dynamic exercise on central haemodynamic variables and cardiac sympathetic nerve activity were studied in 15 patients during both fixed rate ventricular-inhibited (VVI) and QT interval-sensing rate responsive (TX) pacing. Haemodynamic measurements were made at rest, during a mental stress test and during supine exercise at 30 W. Cardiac sympathetic nerve activity was assessed by measuring the arterial and coronary sinus plasma concentrations of noradrenaline (NA) and adrenaline (ADR), the NA kinetics in arterial plasma (radiotracer infusion) and the overflow of NA into the coronary sinus. During exercise the paced ventricular rate increased by 47% with TX. TX provided a higher cardiac output than VVI despite a similar myocardial oxygen consumption and a lower level of cardiac sympathetic activity. Cardiac NA overflow based on 3H-NA extraction over the heart increased from 182 to 1046 pmol min-1 in the VVI mode (P less than 0.01) and from 178 to 793 pmol min-1 in the TX mode (P less than 0.001). The difference in cardiac NA overflow in response to exercise (P less than 0.05 by ANOVA) was not reflected in similar differences in arterial NA concentrations or spill over rates. During mental stress the ventricular rate increased in 12/14 patients. Noradrenaline overflow increased similarly in the two modes. Changes in cardiac NA overflow during mental stress and exercise were correlated with increases in TX pacing rate. This study confirms that both mental and physical stress cause significant changes in cardiac sympathetic nerve activity and central haemodynamic variables, and that the TX pacemaker responds by increasing its pacing rate in a physiological manner. PMID- 2265642 TI - Influence of age and sex on left ventricular volumes and ejection fraction during upright exercise in normal subjects. AB - To determine the effects of age and sex on exercise left ventricular volume indexes and ejection fraction, a cross-sectional study was performed in 18 young volunteers (nine men and nine women) and in 17 older volunteers (nine men and eight women) without evidence of coronary artery disease by exercise electrocardiographic and thallium-201 criteria. All subjects performed a multistage maximal upright exercise with measurements of maximal oxygen consumption and heart rate; left ventricular ejection fraction and absolute volume indexes were measured at rest and during submaximal and maximal exercise using equilibrium radionuclide ventriculography. At rest, no effect of age or sex on any parameter was observed. At peak exercise, an age-related increase in mean blood pressure, end-diastolic and end-systolic volume indexes, and decrease in ejection fraction, cardiac index, heart rate and oxygen consumption were noticed. Sex had a significant effect on maximal workload, maximal oxygen consumption and ejection fraction. PMID- 2265643 TI - Measuring left ventricular dimensions by conductance catheter in the rabbit. AB - A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals. PMID- 2265645 TI - Fistula between a branch of left anterior descending coronary artery and pulmonary artery with spontaneous closure. AB - Communication between a branch of left anterior descending coronary artery and main pulmonary artery is rare and has been previously described. However, spontaneous closure has not been described previously. We report such a case in a 41-year-old man with exertional angina and coronary artery disease. PMID- 2265644 TI - More rapid thrombolysis with coronary venous retroinfusion of streptokinase compared with intravenous administration. An experimental study in canines. AB - The efficacy of coronary venous retroinfusion vs intravenous administration of streptokinase was compared in 20 closed chest dogs with copper coil induced thrombosis of the left anterior descending coronary artery. Streptokinase was continuously infused for 60 min (100 IU kg-1 min-1) starting 60 min after coronary artery occlusion. Time to clot lysis was determined by coronary angiography performed at 5 min intervals. Complete lysis occurred in eight out of 10 dogs receiving intravenous streptokinase and in all 10 dogs in the coronary venous group. Time to thrombolysis was significantly shorter with coronary venous retroinfusion (23 +/- 8 min) than after systemic infusion (62 +/- 26 min; P less than 0.001). Recovery of ischaemic zone left ventricular systolic function, studied by two-dimensional echocardiography, was significantly better in the animals that received retrograde streptokinase than in the group that received intravenous streptokinase (17 +/- 12% vs -2 +/- 16%; P less than 0.05). Myocardial necrosis expressed as a percentage of the risk area was 8 +/- 12% after retroinfusion of streptokinase compared with 32 +/- 25% (P less than 0.005) after intravenous administration. In conclusion, coronary venous administration of streptokinase was more effective than intravenous therapy as determined by more rapid clot lysis which resulted in improved functional recovery of the ischaemic myocardium and a significant reduction in myocardial necrosis. PMID- 2265646 TI - Right atrial, right ventricular and left ventricular thrombi in (incomplete) Behcet's disease. AB - An 18-year-old man presented with a history of oral sores and presence of high fever, scrotal ulcerations and haemoptysis. Multiple mural cardiac masses were present in the right atrium, right ventricle and left ventricle. Furthermore, pulmonary vasculitis with aneurysm formation and venous thrombosis involving the superior sagittal sinus and right transverse sinus were found, and the diagnosis was made of (incomplete) Behcet's disease. While receiving anticoagulation and later, treatment with prednisone and cyclophosphamide, the cardiac thrombi gradually disappeared. We stress the importance of early echocardiography to evaluate cardiac abnormalities in Behcet's disease. PMID- 2265647 TI - A loud third heart sound and asymptomatic myocarditis during Mycoplasma pneumoniae infection. AB - A 20-year-old man had a fever and cough due to Mycoplasma pneumoniae pneumonia. He had no heart symptoms, but auscultation revealed an exceptionally loud third heart sound, suggesting cardiac involvement. Marked myocardial enzyme release, serial electrocardiographic ST-T changes, and transient increase in interventricular thickness and inferior wall hypokinesis at echocardiography supported the diagnosis of acute infectious myocarditis. Recovery was quick. This case shows that acute myocarditis with significant myocardial injury may pass without any subjective heart symptoms. PMID- 2265648 TI - Erythropoietin accelerates the recovery from extreme hemodilution: a randomized, placebo-controlled study in dogs. AB - Six splenectomized beagles of either sex (13.8 +/- 2.2 kg) were randomly treated either with 500 U/kg recombinant human erythropoietin (rhu-EPO) (verum group, n = 3) or an equivalent volume of the vehicle (placebo group, n = 3). Both solutions were given intravenously for 3 days. At day 4 after onset of treatment, the dogs were anesthetized and subjected to isovolemic hemodilution using 6% Dextran 60 (MW 60,000) down to a hematocrit of 0.10. During the recovery period vehicle or rhu-EPO was given every other day until the hematocrit reached control values. Every day venous blood samples were withdrawn, and the hematocrit as well as the concentrations of hemoglobin and 2,3-diphosphoglycerate were determined. In addition, the platelets and reticulocytes were counted. Treatment with rhu-EPO shortened the time of hematocrit recovery from 20 (placebo) to 11 days (p less than 0.05). The reticulocyte count peaked at day 2 (verum) versus day 5 (placebo). These findings indicate a successful stimulation of red blood cell production after extreme hemodilution in animals treated with erythropoietin. Therefore, rhu-EPO may allow to optimize blood donation programs as well as preoperative hemodilution and yield both, higher amounts of autologous blood and an accelerated reversal of dilutional anemia. PMID- 2265649 TI - Acute hypercalcemia and increased work load in canine transplanted heart. Coronary blood flow adjustments. AB - Coronary vasodilator adjustments following cardiac transplantation might be adversely affected during severe rejection. We studied the coronary blood flow response following intravenous bolus administration of calcium (0.04-0.05 mEq/kg) in canine cardiac transplants. Fifteen dogs were submitted to orthotopic heart transplantation and equipped with electronic implants for monitoring of hemodynamic parameters. Of these animals, 9 were not immunosuppressed, while 6 were treated with ciclosporin, azathioprine, and prednisone. The effects of calcium administration upon cardiac function were evaluated during the postoperative period, at recovery (2-3 days after transplantation) and during severe rejection (7-10 days after transplantation), and also in immunosuppressed animals. Rapid calcium administration elicits brief increases in arterial pressure, cardiac index, stroke work, and coronary blood flow. There were significant differences in these effects, depending on the hemodynamic status of these animals. Coronary blood flow was significantly increased in all experiments, except when severe rejection was evidenced. These results indicate that changes in myocardial metabolic demand (work load) are not adequately matched with coronary blood flow adjustments in the presence of severe rejection. PMID- 2265650 TI - Effect of pulmonary blood flow on lung water and pulmonary hemodynamics in the canine lung lobe. AB - The isolated left middle lobes of canine lungs were perfused in situ, by stepwise elevation of the blood flow. The weight gain of the lung lobe per initial bloodless dry lung weight (delta w g/min.IdQ1) showed a significant (p less than 0.001) correlation with the blood flow per body weight (F, ml/min.kg) with a regression line of delta w = 8.3 X 10-4F2.3. The pulmonary venous pressure (Pv) correlated significantly (p less than 0.001) with the pulmonary artery pressure (Pa), i.e. Pa = 11.2 + 1.3 Pv, with a constant left atrial pressure (Pla). The total pulmonary vascular resistance [TPVR = (Pa - Pla)/F] and the small pulmonary artery resistance [SR = (Pa-Pv)/F] decreased by steps with a constant pulmonary venous resistance (VR = TPVR-SR), and VR/TPVR increased by steps as the flow was increased. By incremental blood flow through the restricted lung tissue, we conclude that fluid filtration into the interstitium was flow-dependent, the pulmonary capillaries and precapillaries provided a large capacity for blood flow and the resistance to the flow was directed to the postcapillary site. PMID- 2265651 TI - Combined drug therapy in porcine endotoxemia. Hemodynamic and proteolytic effects of antagonists against histamine, serotonin and endorphin. AB - In order to investigate the importance of potential mediators of pathophysiologic derangements in endotoxemia, we have examined the effects of the combined administration of antagonists against histamine, serotonin and endorphins in a porcine model of endotoxemia. The treatment regimen significantly reduced the increase in pulmonary artery pressure, pulmonary vascular resistance and systemic arterial pressure seen in the early stages of endotoxemia. Also, cardiac output was better maintained. However, the hemodynamic performance after an observation period of 5 h was not statistically different from untreated animals. The treatment regimen did not hinder the activation of the kallikreinkinin and fibrinolytic systems of plasma, which was evident in both treated and untreated animals, and could not counteract the increase in hematocrit or leukopenia seen in this model. This study shows that the combined blocking of histamine, serotonin and endorphines is not enough to abrogate the detrimental effects of endotoxin in a porcine model. PMID- 2265652 TI - Mesenteric venous stenosis reduces hyperammonemia in the portacaval-shunted rat. AB - Hyperammonemia is a constant finding following portacaval anastomosis (PCA), and has been incriminated in the neurologic deterioration observed following portasystemic shunt in humans. We developed a rat model for mesenteric venous hypertension by modification of a commonly used technique for studying extrahepatic portal hypertension. We then examined serum ammonia levels in rats undergoing sham operation, mesenteric vein stenosis (MVS) alone, PCA alone, and MVS plus PCA. All MVS animals had a significant (p less than 0.05) elevation in mesenteric venous pressures 2-3 weeks after operation. Serum ammonia levels were normal in rats undergoing sham operation and MVS, and were significantly elevated (p less than 0.001) in rats with PCA. However, a significant (p less than 0.01) reduction in serum ammonia levels was realized when PCA and MVS were combined. These data suggest that intestinal ammonia absorption is a function of splanchnic venous pressure. These findings may be relevant to the management of the neuropsychiatric deterioration seen following PCA in man. PMID- 2265653 TI - Alterations in the fine structure of the pig liver upon cold ischemia. AB - The fine structure of the pig liver was examined after 30 min of warm ischemia at 37 degrees C, after 2 h of cold ischemia at 4 degrees C and after 30 min of warm ischemia followed by a further 30 min of cold ischemia. After warm ischemia, limited mitochondrial swelling was observed in hepatocytes. After cold ischemia, alone or following warm ischemia, vesiculation and vacuolation of the hepatocyte cytoplasm and appearance of intrasinusoidal blebs deriving from hepatocytes were observed with different intensity among the animals. These findings suggest that cooling and storing the liver at 4 degrees C may lead to injury, which could negatively influence the viability of the organ, with different intensity from case to case. PMID- 2265654 TI - Prolonged preservation of cadaver heart with Belzer UW solution: 24-hour storage system for asphyxiated canine hearts. AB - The efficacy of Belzer UW solution was compared to Collins' solution in the preservation of asphyxiated cadaver hearts in a canine model. Donor hearts were stored for 24 h: 2 h of in situ hypothermic (15 degrees C) coronary perfusion plus 22 h of simple immersion in ice-cold solution. Verapamil, propranolol and prostacyclin were used for myocytoprotection in both groups. After orthotopic transplantation, all animals were weaned off bypass without inotropic support. After 1 h, however, the cardiac output was significantly higher in the Belzer UW solution group (128 +/- 28 vs. 67 +/- 13 ml/kg/min, p less than 0.01). PMID- 2265655 TI - Characteristics of mouse to rat xenograft heart transplantation. AB - A simple technique for grafting a mouse heart heterotopically to rat neck vessels in experimental xenotransplantation is described. In this series, graft survival was tested with the following modes of immunomodulation: ciclosporin (Cy), athymic and nude rats, splenectomy, total lymphoid irradiation (TLI), 15 deoxyspergualin in two different doses and various combinations of these. The mean graft survival time, with Cy or athymic and nude rats as recipients, was 3 days as also seen in animals without treatment. With either irradiation, splenectomy or 15-deoxyspergualin, 10 mg/kg daily, the graft survival time was prolonged to 7.8, 4.7 and 6.8 days, respectively. In combination, TLI + splenectomy gave a graft survival of 9.7 days and Cy + splenectomy 7.2 days. With 15-deoxyspergualin at 10 mg/kg/day plus splenectomy, done 1 week prior to transplantation, graft survival was extended to 17.8 days. PMID- 2265656 TI - Combined treatment of adriamycin and dipyridamole inhibits lung metastasis of B16 melanoma cells in mice. AB - The combined effects of adriamycin (ADM) and dipyridamole (DP) on lung metastasis of B16 melanoma cells in mice were investigated. First, the antitumor effects of ADM and DP were examined both in vitro and in vivo. The clonogenicity of B16 melanoma cells was suppressed by the combination of ADM and the nontoxic dose of DP in vitro, and growth of the B16 melanoma solid tumor implanted subcutaneously in mice was inhibited with this drug combination, compared to findings with ADM alone in vivo. To examine events related to experimental lung metastasis, 2 X 10(5) B16 melanoma cells were given intravenously into the tail vein of mice and the efficacy was determined by counting the number of metastatic tumor nodules. DP in doses of 25-100 mg/kg given alone reduced the number of metastasis to about 85% that in the control group. ADM in doses of 1-4 mg/kg for 3 days inhibited the metastasis, in a dose-dependent manner. When combined with DP, the antimetastatic effect of ADM was enhanced and the number of metastasis prominently decreased, compared to single application of the drug (p less than 0.05). We speculate that ADM given concomitantly with DP may have the potential to inhibit metastatic growth of a tumor. PMID- 2265657 TI - Evidence that ciclosporin is hepatotoxic and hepatotrophic in 70% hepatectomized rats and mice. AB - The influence of ciclosporin (Cs) on liver regeneration was studied in rats and mice with or without thymus after two-third hepatectomy. Rats were treated at 24, 0, and +24 h posthepatectomy with oral Cs, 5, 10, or 20 mg/kg. Before hepatectomy, mice were given a 4-day course of Cs 10 mg/kg. The peak mitosis (30 h posthepatectomy) of remnant hepatocytes in rats was doubled by the two lower dosages of Cs but was suppressed by the highest dosage compared with control. In addition, the rise in serum transaminase and total bilirubin concentrations was proportionate to the increase in Cs dosage given. Cs increased hepatocyte division in thymic mice but was hepatotoxic in athymic nude mice. These data present evidence that Cs is both hepatotrophic and hepatotoxic in regenerating liver. PMID- 2265658 TI - Decrease in hepatic mitochondrial redox state by massive infusion of citrate phosphate-dextrose solution in jaundiced rabbits. AB - To clarify the mechanism of metabolic derangement by massive blood transfusion to the damaged liver, the changes in the hepatic mitochondrial redox state, as reflected in arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), were studied in jaundiced rabbits by infusion of massive citrate-phosphate-dextrose (CPD) solution. The jaundiced rabbits received common bile duct ligation (BDL group), and the sham group had a simple exploration of the bile duct. CPD solution was infused for 3 h at a rate of 9 ml/kg/h in each group. As metabolic parameters, blood gas, pyruvate, lactate, citrate and ketone body ratio were analyzed in the arterial blood. During the course, arterial ketone body ratio decreased significantly (p less than 0.01) in the BDL group with severe metabolic acidosis, while it was maintained at high value in the sham group with metabolic alkalosis. Organic acids were more highly accumulated in the BDL group than in the sham group. These results suggested a hepatodepressant effect of massive blood transfusion, especially in the damaged liver. PMID- 2265659 TI - Detrusor sphincter dyssynergia syndrome. A new syndrome and its treatment by external sphincter myotomy. AB - A new syndrome in which there was persistent external anal sphincter contraction on rectal distension is described in 18 patients. 12 were females and 6 males. Average age was 38.3 years. The main complaint was chronic constipation and straining at stool. Rectal evacuation was performed manually or by enemas. Investigations comprised manometric and EMG studies of external anal sphincter. The average number of stools per week was 2.1. Rectal neck pressure recorded normal values at rest and on squeeze. The rectoinhibitory reflex registered high rectal neck pressure on rectal distension [average 136 +/- (SD) 12.3 mm Hg] which was lowered (average 13 +/- 2.2 mm Hg) after pudendal nerve block. External sphincter showed persistent high EMG activity during rectal distension. External sphincter myotomy was performed in 16 patients. Myotomy specimens showed no histologic abnormalities. The patients were followed up for 2-4 years after the operation. The stool frequency approached the normal range, and straining at stool disappeared. Rectal neck pressure during rectal distension dropped to normal values (average 36 +/- 10.3 mm Hg). Control disorders occurred in 2 patients but disappeared within 6 months after myotomy. External sphincter contraction on rectal distension leads to rectal neck obstruction with a resulting constipation and straining at stool. The cause of this contraction is unknown. Myopathy is excluded by the normal muscle integrity as evident from the normal EMG and biopsy findings. A disorder of the reflex arc may be considered. PMID- 2265660 TI - Relationships among personnel tests, age, and job performance. AB - Relationships among an information-processing based test battery, job performance, and age were examined using a sample of petroleum transport drivers. The results suggest that when age differences in job performance occur, they can be better explained by performance on valid predictors rather than age per se. The findings are discussed in the context of moderated models of job experience, the Age Discrimination in Employment Act (ADEA), and the erroneous use of age as a surrogate measure in personnel decision making. PMID- 2265661 TI - Some determinants of attrition in prospective studies on aging. AB - Demographic measures, psychosocial variables, and objective and subjective measures of physical impairment were assessed in elderly men twice at intervals of 12 to 18 months. Canonical discriminant function analysis of the relationship between these predictor variables on the first testing and whether participants (a) returned for retesting, (b) did not return because of apparent disinterest, or (c) did not return because of illness or death, revealed two significant canonical variates. The first, characterized by decreased mental and physical capacity, discriminated between the deceased/ill group and the other two groups. The second was characterized by decreased social interaction and life satisfaction, and increased life events, and distinguished between the disinterested group and the other two groups. However, both groups that failed to return for retesting showed evidence of impaired physical health and a general disengagement from social and personal activities, compared to the retested group. PMID- 2265662 TI - Latitude of choice and well-being in institutionalized and noninstitutionalized elderly. AB - While important positive effects on the psychological and physical well-being of the elderly often result from increased perceived and actual personal control, the literature also reflects many inconsistent findings. The lack of consensus on aging and the psychology of control has been variously attributed to differences in methodology, measurement devices, theoretical assumptions and the impact of moderator variables. To help bring order to this area the present study evaluated the Latitude of Choice model to determine whether Latitude of Choice scores differ across living arrangements, gender or age. Analysis of covariance tests, controlling for measures of education, perceived health and economic satisfaction, yielded significant main effects but no significant interactions. Partial correlations between Latitude of Choice and measures of psychological well-being, for the total sample and each of the main effect samples, were all significant. These findings provide substantive support for the theoretical approach that underlies Latitude of Choice as a measure of personal control of everyday activities and the potential value of personal control as a moderator of well-being in different environments. PMID- 2265663 TI - Visual and auditory modality and suffix effects in young and elderly adults. AB - Research has shown that elderly as compared with young adults show relative deficits both in processing visually as compared with auditorily presented stimuli and in tasks having attentional components. In this study, visual and auditory presentation was compared in young and elderly adults using the suffix paradigm in which the control condition involves immediate serial recall and the experimental condition, a suffix, a not-to-be-remembered final item. The standard finding in this paradigm is called the modality effect, superior auditory as compared with visual performance in the control condition which is localized at the end of the sequence. Generally, auditory suffixes following auditory sequences reduce the modality effect while visual suffixes following visual sequences do not. The results showed generally standard modality and suffix effects for both age groups. Relatively inferior performance was present in the elderly in the visual as compared with the auditory control conditions suggesting recoding deficits in this group. Auditory suffixes following auditory sequences had a relatively greater performance effect on the elderly than the young, while visual suffixes following visual sequences did not impair the performance of either group. This suggests a modality specific attentional deficit in the elderly. Rank order correlations suggest that individuals within both age groups showing large differences in performance between auditory and visual control conditions may have relative recoding difficulties for their age. Additionally, increased susceptibility to auditory interference for elderly as compared with young subjects may be a marker of aging, while relative within-group susceptibility to auditory interference may be a deficit on the part of young subjects. PMID- 2265664 TI - Cognitive effort in modality retrieval by young and older adults. AB - A secondary task methodology was used to determine whether the retrieval of modality information is more cognitively effortful for older adults than younger ones. Young (M age = 20 years) and older (M age = 68 years) adults were asked to learn a mixed modality (auditory and visual) list of nouns. During recall of words and modality, subjects were asked to respond to a randomly presented light signal. Cognitive effort for the primary task (recall) was measured by interference with the signal detection task. Adding a modality identification task to word retrieval did not significantly increase cognitive effort for either age group, although young adults were better at both word and modality recall and word recall itself was more effortful for older adults. Results suggest that age decements in modality learning cannot be explained by greater cognitive effort during retrieval of information about modality. PMID- 2265665 TI - Age differences in components of metamemory. AB - Young adults (N = 58) and older adults (N = 55) answered 30 questions extracted from three dimensions of the Metamemory in Adulthood (MIA) questionnaire: Capacity, Task and Strategy. The older participants scored significantly lower on the Capacity dimension, indicating that they report having greater difficulty in everyday memory situations. There was no age difference on any item in the Task dimension; both groups were equally knowledgeable about memory task demands. Responses to Strategy items varied with type of strategy: younger adults were more likely than older adults to report the use of encoding strategies, while older adults reported significantly more use of strategies which involved planning and organization. A further group of employed young adults (N = 26) was added to clarify the respective roles of aging and environmental demands on strategy use. The findings suggest that both changes in lifestyle and the effects of aging per se play some part in the use of particular memory strategies. PMID- 2265666 TI - Age differences in the effects of background noise on motor and memory performance in a precision sport. AB - Young (M = 27.8 years) and older (M = 53.2 years) highly skilled miniature golf players were observed in competitions in which the background noise was either tape-recorded traffic sounds or a radio broadcasting a soccer game. Varying in meaningfulness, the two conditions were examples of types of noise which prevail during normal competitive activity in miniature golf. Measures of motor performance, arousal, and memory for shots were registered. Results showed that players played less well and remembered fewer shots under the radio broadcasting condition than in the traffic noise condition; whereas younger players performed equally well for both measures in both noise conditions. In neither age group was the level of arousal affected by type of noise. The results suggest that there may be an age-related impairment in selective attention situations, and, in contrast to past findings, also when the task does not demand that the irrelevant noise stimuli be searched. A claim is made that the benefit of domain-specific expertise in older people is reduced in situations of high arousal or increased cognitive demands. PMID- 2265667 TI - Age differences in the temporal continuity of gratings as a function of their spatial frequency. AB - This study compared young and elderly observers on the continuity of sinusoidal grating-pairs as a function of interstimulus interval (ISI) and spatial frequency (.5, 1.0, 2.0, 4.0, 8.0, and 12.0 c/deg). Consistent with prior research, the maximum ISI over which pattern continuity was maintained increased with spatial frequency. In addition, among older observers, grating continuity occurred at significantly longer ISI's at the two lowest spatial frequencies; no age difference was observed at the higher spatial frequencies. These results could not be attributed to an age difference in retinal illumination associated with pupillary miosis. However, they do indicate an age-related decline in detecting visual offset and are consistent with the hypothesis of a decline in the effectiveness of the transient visual channels. PMID- 2265668 TI - Young and older adults' metaphor interpretation: the judgments of professionals and nonprofessionals. AB - Thirty young and 30 older adults provided interpretations for eight metaphors presented in written form. In Part A of the study, five experienced English teachers rated all interpretations (blind with regard to age of respondent) on a 7-point scale anchored with the terms "literal" and "poetic". The professionals' ratings were no different for the young and older adult subjects' responses, suggesting maintenance with age of this ability. In Part B of the study, 16 young and 16 older adult nonprofessionals rated a statistically representative subset of the metaphor interpretations (again, blind with regard to age of respondent). Their 7-point rating scale was anchored with the global terms "very poor" and "excellent". There was no overall difference in young and older nonprofessional adults' judgments. However, there was a Rater Age x Respondent Age interaction. The older nonprofessionals gave equivalent ratings to the metaphor interpretations of young and older adult respondents. The young nonprofessionals assigned significantly higher ratings to the young respondents' metaphor interpretations than to the older respondents' metaphor interpretations. PMID- 2265669 TI - Subjective ordering, working memory, and aging. AB - Cognitive decline in aging was studied by presenting four tasks involving short term memory to young and old adults: digit span forward, missing scan, randomization span, and randomization span visual. Results showed that performance declined significantly with age in the latter two tasks, which require subjective ordering of a sequence of responses, and not in the first two tasks, which involve reproduction of a presented sequence and searching and comparison processes. PMID- 2265670 TI - Slowness in elderly gait. AB - The aim of this research was to better understand how gait slows with age. We analyzed the kinematic parameters of locomotion (velocity, stride length, cycle duration, swing and double support durations), and their interrelationships both in the slowing process due to aging and in intentional modulations of velocity. The experiments were carried out on a group of 67 elderly adults (aged 60 to 80+) walking with a free gait and a fast gait. This group was compared to a young population in equivalent situations. The results show that the main characteristics of the elderly gait are the shortening of strides and the increasing of the double support phase. However, these properties seem to be due to the slowness of the elderly gait more than to more specific alterations affecting this population since identical features were also observed in the slow gait of the young subjects. Furthermore, the ability to intentionally modulate velocity observed in this study was not altered by aging. These results suggest that elderly gait can be said to be normal if one takes the velocity into account. PMID- 2265671 TI - The effect of goal-setting and feedback on age differences in secondary memory. AB - Goal-setting and feedback have been found to improve performance on a variety of tasks. The present study applied this finding to an examination of adult age differences in secondary memory. Elderly and young adults completed a free-recall task in which one subgroup established a performance goal for blocks of trials and received feedback on a trial-by-trial basis. A second, comparison subgroup completed the same task without setting goals or receiving feedback. Results indicated that the use of the motivational technique of goal-setting and feedback increased memory performance of both age groups beyond that obtained under standard recall conditions. PMID- 2265672 TI - Changes in analogical reasoning in adulthood. AB - This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill). PMID- 2265673 TI - Systemic human diseases as oxidative risk factors in cataractogenesis. II. Chronic renal failure. AB - In this study we have investigated the oxidative metabolism of red cells (RBC), plasma, serum and aqueous humour of healthy subjects and of age-matched cataractous patients with and without chronic renal failure (CRF). Reduced glutathione (GSH) levels in RBC were lower in CRF patients than in the other groups. Oxidized glutathione (GSSG) plasma levels in CRF patients were higher than those of controls and cataractous subjects. The activity of the enzyme glucose-6-phosphate dehydrogenase in RBC was significantly reduced in CRF patients with respect to the other two groups. The levels of malondialdehyde (MDA) in RBC and in lens were about twice in CRF patients compared with the other two groups. The plasma levels of vitamin E were diminished in CRF patients; on the contrary, the biological liquid oxidant activity (BLOA) of serum in CRF patients was significantly higher than in controls and in cataractous patients without CRF. Cataractous patients with and without CRF showed similar levels of GSH in aqueous humour; on the contrary, the content of GSSG was significantly higher in CRF patients. Our findings seem to demonstrate that CRF patients are exposed to oxidative stresses that could probably act synergistically with uraemia and carbamylation of lens proteins. This synergism could explain why CRF represents a relatively high risk factor for cataract. PMID- 2265674 TI - Effect of species differences and dietary vitamin C on the concentration of ascorbate- and acid-soluble thiol in fish eye. AB - Data presented confirm the essentiality of modification of the dinitrophenylhydrazine (DNPH) method to analyze the total ascorbic acid and dehydroascorbic acid in ocular tissues and stress the need of corrections for the interfering substances. Variations in ascorbate and thiol concentrations in the lens, retina and aqueous humour of freshwater fish belonging to the Cyprinidae family were examined. The interspecific variability of ascorbate concentration was highest in the aqueous humour and lowest in the retina. The high ascorbate concentration in the retina seems to reflect the importance of the sense of vision in fish life-style as compared to chemo- and acoustico lateralis senses. The regional distribution of the total ascorbate is in the order of decreasing concentrations: retina, lens and aqueous humour. However, the retinal ascorbate is almost exclusively in the oxidized form, and the lenticular ascorbate is almost exclusively in the reduced form. Thiol concentration in the lens is five- to tenfold that in the retina and aqueous humour. This explains the oxidation status of ascorbate in different eye compartments of the eye. After 30 days on diets containing various levels of ascorbic acid or ascorbic acid sulphate, the ascorbate concentration in the eye compartments of common carp (Cyprinus carpio L.) was determined. Ocular tissue can be used to monitor the development of the ascorbate status in fish, and the retina is the most responsive tissue to the enhanced or depleted ascorbate levels. PMID- 2265675 TI - Long-term culture and characterization of human limbal microvascular endothelial cells. AB - Human limbal explants obtained from 44 eyebank donors were cultured in medium 199 supplemented with 20% fetal bovine serum, vascular endothelial cell growth supplement and heparin. Cells grew abundantly out of the explants. They initially formed a 'cobblestone' patterned monolayer but later exhibited an elongated morphology with growth in parallel bundles. These cells could be passaged at least nine times and were identified throughout the consecutive passages as microvascular endothelial cells by the expression of factor VIII-related antigen, laminin and of the H determinant of ABO blood groups. As expected from vascular endothelial cells, flow cytometric analysis demonstrated a strong expression of class I histocompatibility antigens and a weaker expression of class II antigens. Class II antigen expression was enhanced by culturing the cells in the presence of immune interferon. These cells produced immunoreactive interleukin-1, mainly of the alpha type, under endotoxin stimulation. Limbal microvascular cells could be useful to study corneal angiogenesis. Furthermore, long-term culture of limbal cadaveric tissue can potentially be used to characterize donor-specific immunologic responses in corneal graft recipients. PMID- 2265676 TI - Scanning electron microscopic study on the vasculature of the human anterior eye segment, especially with respect to the ciliary processes. AB - The architecture of the vasculature of the human anterior eye segment was studied by scanning electron microscopy of vascular resin casts. Regarding the major vessels it was found that the perforating branches of the anterior ciliary arteries (ACA) form an anastomozing circle which lies in the posterior portion of the ciliary muscle (intramuscular circle). The ACAs supply the outer and posterior parts of the ciliary muscle, partly the iris, and the peripheral choroid by recurrent ACA branches. The major arterial circle of iris (MACI) which lies more anteriorly is formed mainly by the long posterior ciliary arteries and supplies the inner and anterior portion of the ciliary muscle, the iris and the ciliary processes. The ciliary process vasculature consists of three different vascular territories with discrete arterioles and venules. The first vascular territory which is located at the anterior end of the major processes, is drained posteriorly by venules which pass the ciliary body without greater connections to the venules of the major ciliary processes. The second and third territories comprise the vasculature of the major and minor ciliary processes drained posteriorly by venules which are located at the margin of the ciliary processes. In supravital experiments with human autopsy eyes, a characteristic segment of arterioles supplying the first and second territory was found to be constricted after immersion with epinephrine in a similar way as in cynomolgus monkeys in vivo. Although the general arrangement of the ciliary process vessels is similar to that of the cynomolgus monkey, there are characteristic differences in the size of the territories and in the pattern of the capillary networks. The division of the ciliary process vasculature into three vascular territories may reflect a functional differentiation in the process of aqueous humour production. PMID- 2265677 TI - Mechanisms of photochemically produced turbidity in lens protein solutions. AB - Calf alpha- and gamma-crystallin were photolyzed in 1-2 mg ml-1 aqueous solutions, using both laser and conventional UV radiation in the 297-320 nm wavelength region. Gamma-crystallin solutions became highly turbid upon UV irradiation, while alpha-crystallin developed no turbidity when irradiated under identical conditions. The photolyzed solutions were analyzed by SDS-PAGE. These gels revealed loss of normal 20 kDa polypeptide, and formation of higher molecular weight peptides, in both alpha- and gamma-crystallin, presumably as a result of photocross-linking reactions and/or protein insolubilization. Thus, although both crystallins underwent photocross-linking, significant turbidity production only occurred in gamma-crystallin. Some possible explanations for these differences are proposed, with one possibility being that most photocross links in alpha-crystallin occur between subunits of the 1000-kDa oligomer, while in gamma-crystallin the cross-links occur between 20-kDa monomer units. Hence, cross-linking in alpha-crystallin does not affect the average size of particles in solution (or the turbidity), while cross-linking in gamma-crystallin results in a significant increase in average particle size with concomitant increase in turbidity. Another possible explanation is that UV-irradiated gamma-crystallin becomes insoluble (due to charge changes resulting in non-covalent aggregation) while alpha-crystallin does not. Other differences in the photochemical behavior of alpha- vs. gamma-crystallin were noted--gamma-crystallin photolysis rate was about 50% greater than alpha-crystallin. Alpha-crystallin photolysis yielded strong NFK-like fluorescence, while gamma-crystallin did not. One similarity was that photolyzed alpha- and gamma-crystallin lost amino acids His and Trp at about the same rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2265678 TI - Identification of methionine enkephalin in the bovine cornea by fast atom bombardment-mass spectrometry. AB - Native methionine enkephalin and methionine enkephalin generated proteolytically from a larger peptide were both identified and quantified from bovine cornea by negative ion fast atom bombardment-mass spectrometry. The corneal peptides were purified initially be reverses-phase high performance liquid chromatography and identified tentatively by radioreceptor assay and/or radioimmunoassay. PMID- 2265679 TI - Horizontal cell axon terminals in growing goldfish. AB - In the retina of teleost fish, cone horizontal cell axons penetrate the inner nuclear layer, where they enlarge into fusiform terminal swellings. The present study shows that horizontal cell axon terminals enlarge disproportionately during postembryonic growth of the retina in juvenile and adult goldfish: the relative volume of axon terminals increases almost 20-fold, while the volume of the entire retina increases only about fourfold during a 2-3-yr period. The enlarging axon terminals fill in the gaps created as the numerical density of nuclei in the inner nuclear layer falls. Horizontal cell axon terminals are thought to participate in cone-dominated visual pathways, although their precise role is unclear. The results of this study suggest that a comparison of horizontal cell function in small and large fish might help to resolve this issue. PMID- 2265680 TI - Immunogold localization of type IV collagen and laminin in the aging human outflow system. AB - Tissue from the outflow system of six surgically enucleated aged eyes was used for an ultrastructural immunocytochemical study of the distribution of laminin and type IV collagen. The immunogold technique provided precise localization of laminin beneath lining endothelial cells of the inner wall of Schlemm's canal. Laminin labelling was absent in the trabecular beams. Type IV collagen was found in the basement membranes of the trabecular beams and in fine filamentous basement membrane material in the cribriform layer. Electron dense plaques in the cribriform layer labelled positively for laminin in the outer coarse fibrillar zone but not in the electron dense core. Long-spacing collagen was negative for type IV collagen. PMID- 2265681 TI - Effect of acetylation by aspirin on the thermodynamic stability of lens crystallins. AB - To assess the effect of aspirin on cataractogenesis, we compared the stability of individual, native protein fractions alpha L, beta H, beta L, beta s, beta B2, gamma-II, gamma-III and gamma-IV with that of their acetylated counterparts. The conformational stabilities of native fractions beta B2 and beta s, which were not reported earlier, were determined first from their thermal and a thermal denaturation behaviour. Since alpha L, beta H and beta L fractions are oligomeric, no thermodynamic analysis of these fractions was attempted. The thermal stability of beta s and beta B2 is rather low; their melting temperature (T1/2) range is 58-60 degrees C compared with 67-75 degrees C for the gamma crystallins. Furthermore, except for alpha L, which remains stable even at 100 degrees C, and beta B2, all crystallins aggregate at temperatures slightly above T1/2. The Gibbs free energy of unfolding, delta GH2OD, calculated from guanidine HCl (GdnHCl) denaturation, is surprising low (3-9 kcal mol-1) for all crystallin fractions. The low values of delta GH2OD indicate that the structural destabilization of these proteins, which may lead to cataract formation, could result from a slight disturbance of a particular kind (sugar, UV light, oxidation, and other factors). The overall effect of acetylation on the individual crystallin fractions is mixed. The thermal stability of beta B2 increased, tended to decrease in the case of gamma-crystallins, but remained virtually unchanged for other proteins. Delta GH2OD values of the native crystallin fractions do not differ significantly from those of their acetylated counterparts. PMID- 2265682 TI - The level of spontaneous myogenic tone in isolated human posterior ciliary arteries decreases with age. AB - The spontaneous myogenic activity of rings of human posterior ciliary arteries was studied in vitro. All arteries from six patients had an intrinsic myogenic tone, which was dependent on extracellular calcium and inversely correlated with age. The myogenic tone was stable without rhythmic variations, except in one artery. The level of spontaneous myogenic tone was higher in vessels where the endothelium was removed than in normal arteries. Acetylcholine induced a complete and concentration dependent relaxation of endothelium-intact but not endothelium denuded arteries. Indomethacin induced a small concentration dependent contraction of the arteries. Methylene blue did also contract the arteries concentration dependently. The experiments indicate that the myogenic tone of human posterior ciliary arteries is regulated by prostaglandin formation (prostacyclin?) as well as release of endothelium-derived relaxing factor in the arteries. The results indicate that the blood flow regulatory capacity of these arteries may be endangered by aging and endothelial damage, which could increase the probability of developing, e.g. ischemic damage of the optic nerve head. PMID- 2265683 TI - Uptake, processing and release of retinoids by cultured human retinal pigment epithelium. AB - Upon absorption of a photon, the 11-cis retinaldehyde chromophore of rhodopsin is isomerized and reduced to all-trans retinol (vitamin A) in the photoreceptor outer segments, whereupon it leaves the photoreceptors, and moves to the retinal pigment epithelium (RPE). To clarify the function of the RPE in the regeneration of 11-cis retinaldehyde, we delivered all-trans retinol to monolayer cultures of human RPE. During delivery the retinol was associated with its putative natural carrier, interphotoreceptor retinoid binding protein (IRBP). IRBP has been proposed as a carrier protein involved in the exchange of retinoids between the photoreceptors and the retinal pigment epithelium. The retinoid composition of RPE cells and culture medium was analyzed by HPLC following several incubation periods. The RPE monolayer was found to process all-trans retinol into two distinct end-products: all-trans retinyl palmitate, which remained within the RPE monolayer: and 11-cis retinaldehyde which was released into the culture medium. These results demonstrate retinoid isomerase, retinol oxidoreductase and retinyl ester synthetase activity in human RPE cells cultured under the appropriate conditions. They show that IRBP can serve as a carrier of retinol through an aqueous medium to the RPE, and they illustrate that the visual cycle can be studied in vitro. PMID- 2265684 TI - In vitro characterization of the mechanical properties of canine ophthalmociliary artery. AB - The form and magnitude of K+ Krebs-induced contractures has been measured for the dog ophthalmociliary artery. Ring segments of the vessel were mounted in a myograph after the method of Hogestatt, Andersson and Edvinsson (1983, Acta Physiol. Scand. 117, 49-61). For low passive tensions the K(-)-induced contractures show both a phasic and tonic component, with the tonic tension component being the smaller. As passive tension is increased, the phasic component grows and plateaus whilst the tonic component continues to increase. For high passive tensions the phasic component disappears and the tonic component reduces in magnitude and the contracture is not fully reversible. Comparison of the length tension curves measured during K+ Krebs-induced contractures and Ca2(+)-free Krebs-induced relaxation shows that the active tension generated by this vessel increases with increasing passive tension until a peak active tension of 3.1 mN mm-1 is reached at an effective radius of 357 microns. For greater values of passive tension the active tension decreases. The calculated transmural pressure required to maintain the vessel at this optimal radius is 51.9 mmHg, which is very similar to the only available measurements of ophthalmic artery pressure, viz. 51.8 mmHg (Grunwald, Sinclair and Riva, 1981, Invest. Ophthalmol. Vis. Sci. 20, 564-6). The optimal passive stretch to apply to these ring segments for further pharmacological or physiological work is discussed. PMID- 2265685 TI - Corticosteroids induce a sialated glycoprotein (Cort-GP) in trabecular cells in vitro. PMID- 2265686 TI - A method for determining rhodopsin bleaching rates in situ. PMID- 2265687 TI - An architecture for the fusion site of influenza hemagglutinin. AB - The recent finding that more than one Influenza hemagglutinin (HA) is required at the fusion site for HA-expressing fibroblasts, together with the crystal structure of HA at neutral pH, provide the basic elements of a plausible model for this fusion site. Within an aggregate of HA trimers at low pH, we propose fusion intermediates which are based upon a minimal alteration to the known neutral pH structure of HA and which should have reasonable activation energies. This is the first model of a glycoprotein-mediated fusion site which explicitly accounts for the disposition of the lipids within these intermediates. While the fusion site created by HA will not be the same as that of eukaryotic fusion complexes, general characteristics could be shared. PMID- 2265688 TI - Refilling of endothelial calcium stores without bypassing the cytosol. AB - The present study was undertaken to define the route of Ca2+ used for refilling of intracellular Ca2+ stores in endothelial cells. Ca2+ stores, after emptying with bradykinin in Ca2+ free solution and termination of the stimulation with the bradykinin antagonist, Hoe 140, were allowed to refill by addition of Ca2+. Refilling was prevented by 2,5-di(tert-butyl)-1,4-benzohydroquinone (BuBHQ), an inhibitor of microsomal Ca2+ sequestration. BuBHQ induced large increases in the cytosolic Ca2+ concentration during the refilling phase. This finding is not compatible with a model proposing Ca2+ uptake into the stores directly from the extracellular space but provides evidence for uptake from the cytosolic compartment. PMID- 2265689 TI - Rate-determining steps in penicillopepsin-catalysed reactions. AB - The hydrolysis of Ac-(Ala)2-Lys-Nph-(Ala)2-amide (II) by penicillopepsin is characterized by a solvent isotope effect of 2.11, whereas the hydrolysis of Ac Lys-Nph-amide (I) shows no solvent isotope effect. The dependence of the isotope effect on the concentration of D2O in H2O for substrate II is not linear and suggests that two or more protons are involved in its rate-determining step. We propose that for substrate I the rate-determining step is the distortion of the scissile bond towards a tetrahedral configuration, and for substrate II a conformational change induced by the occupation of the S3 pocket in the enzyme. PMID- 2265690 TI - Proteolytic activation of a bovine brain protein with phosphatidylinositol transfer activity. AB - We have purified a 38 kDa protein from bovine brain which is cross-reactive with an affinity purified antibody against the 35 kDa phosphatidylinositol transfer protein from the same source. Controlled trypsinization of the 38 kDa protein yielded an immunoreactive protein of 35 kDa which displayed a 6-fold increase in phosphatidylinositol transfer activity and a 10-fold higher affinity for this phospholipid. The possibility that the 38 kDa protein is a precursor of the phosphatidylinositol transfer protein is discussed. PMID- 2265691 TI - Oxidation of coniferyl alcohol by cell wall peroxidases at the expense of indole 3-acetic acid and O2. A model for the lignification of plant cell walls in the absence of H2O2. AB - The oxidation of coniferyl alcohol (CA), a lignin precursor, by cell wall peroxidases may take place at the expense of indole-3-acetic acid (IAA) and O2, and in the absence of H2O2. The peroxidase-catalyzed oxidation of CA shows an optimum at an IAA concentration of 0.33 mM, while higher IAA concentrations are inhibitory. The observation that the oxidation of CA by cell wall peroxidase at the expense of IAA and O2 is inhibited by genistein, a putative endogenous inhibitor of lignification in lupin hypocotyls, supports the view that the H2O2 generating system coexists with cell wall peroxidase activities involved in lignification, and that it takes place at the expense of IAA and O2. PMID- 2265692 TI - Sequence identity between human pancreatic cholesterol esterase and bile salt stimulated milk lipase. AB - Three overlapping cDNA clones covering the entire primary sequence of the bile salt stimulated lipase in human milk were isolated from a human breast lambda gt10 cDNA library by screening with the rat pancreatic cholesterol esterase cDNA. Nucleotide sequencing of the cDNA showed that the human milk lipase mRNA encodes a 748-residue protein, including a 23-residue signal peptide. The human milk lipase cDNA is highly homologous to rat pancreatic cholesterol esterase, suggesting that the milk lipase may be identical to the cholesterol esterase in human pancreas. This conclusion was confirmed by isolation and sequencing of the cDNA for human pancreatic cholesterol esterase. Analysis of the sequence for the human cholesterol esterase/milk lipase revealed similarities to other serine esterases in three distinct regions of the protein. These domains may represent the active site triads of these proteins. PMID- 2265693 TI - Human tRNAGlu genes: their copy number and organisation. AB - The tRNAGlu gene copy number, determined by genomic blot analysis of human placental DNA, is approximately thirteen. These studies, using several probes and DNA digested with several restriction enzymes singly or in combination, show that most of these tRNAGlu genes are flanked by DNA of very similar sequence for at least 5 kb. This conclusion is supported by the close similarity of the restriction maps of two lambda Charon-4A recombinants of human genomic DNA containing two different tRNAGlu genes. PMID- 2265694 TI - Proteolysis of Bacillus stearothermophilus IF2 and specific protection by GTP. AB - Translation initiation factor IF2 from Bacillus stearothermophilus (741 amino acids, Mr = 82,043) was subjected to trypsinolysis alone or in the presence of GTP. Following electroblotting and automated amino acid sequencing of the resulting peptides, the location and the sequential order of the main cleavage sites were identified. Trypsinolysis of IF2 ultimately generates two compact domains: a 24.5 kDa C-terminal fragment and a 40 kDa G-fragment which is obtained only in the presence of GTP which strongly protects a cleavage site within the GTP binding domain. PMID- 2265695 TI - Diphosphorylation of myosin light chain in smooth muscle cells in culture. Possible involvement of protein kinase C. AB - Prostaglandin (PG) F2 alpha (30 microM) stimulated both monophosphorylation and diphosphorylation of myosin light chain (MLC) in a smooth muscle cell line (SM 3). The diphosphorylation was significantly decreased by treatment with the protein kinase C inhibitor staurosporine (30 nM, 30 min) from 20.1% of total MLC to 4.5%. The protein kinase C down-regulation treatment of SM-3 cells with phorbol dibutyrate suppressed to 8.7% the MLC diphosphorylation activity in the SM-3 cells. This down-regulation treatment had little effect on the monophosphorylation. We propose that the MLC diphosphorylation in PGF2 alpha stimulated SM-3 cells in culture may be regulated through mechanisms sensitive to protein kinase C. PMID- 2265697 TI - Activation of red cell Ca2(+)-activated K+ channel by Ca2+ involves a temperature dependent step. AB - We found that vanadate-induced 45Ca2+ uptake by red cells is maximal at 25 degrees C. At this temperature, the Cai-induced increase of the K+ permeability (the Gardos effect) shows a lag (up to 8 min) which is not observed at 37 degrees C. This cannot be explained by the lack of availability of Ca2+ for the Ca2(+) activated K+ channel, and suggests that its activation by Ca2+ is mediated by a temperature-dependent mechanism which remains unknown so far. The lag is not observed when the Gardos effect was initiated by propranolol. This shows that the putative temperature-dependent step is different from chloride transport. PMID- 2265696 TI - The inhibition by pertussis and tetanus toxins of evoked catecholamine release from intact and permeabilized bovine adrenal chromaffin cells. AB - Pertussis toxin stimulates both basal and nicotine-evoked catecholamine secretion from intact bovine adrenal chromaffin cells, as well as Ca2(+)-evoked release from permeabilized cells. Tetanus toxin inhibits all these effects; it reduces the secretion of intact cells treated with pertussis toxin to the basal level, and decreases by about 50% Ca2(+)-evoked release from permeabilized cells whether or not previously stimulated by pertussis toxin. PMID- 2265698 TI - Kinetic study of esterification by immobilized lipase in n-hexane. AB - The kinetic of the esterification of oleic acid by ethanol catalyzed by immobilized lipase of Mucor miehei in n-hexane as a solvent has been completely studied. The kinetics of the reaction are suggested to agree with a Ping-Pong Bi Bi mechanism in which only inhibition by excess of ethanol has been identified. Values of all apparent kinetic parameters were computed. No evidence of any significant external diffusional limitation which could account for these values has been detected. Optimization of water content through distribution ratio of water between solvent and support was examined. PMID- 2265699 TI - Agonist-induced down-regulation of m1 muscarinic receptors and reduction of their mRNA level in a transfected cell line. AB - Agonist-induced reduction in both the number of m1 muscarinic receptors and the mRNA coding for the receptor protein was investigated in Chinese hamster ovary (CHO) cells which were transfected with the m1 muscarinic receptor gene. Receptor concentration was measured by the specific binding of the muscarinic ligand, [3H]quinuclidinyl benzilate ([3H]QNB), and Northern blot hybridization analysis was used to evaluate the levels of receptor mRNA. Incubation of cells with 1 mM of the muscarinic agonist, carbamylcholine (CBC), for 24 h decreased receptor density and mRNA levels in cells by 65% and 73%, respectively. These results indicate that agonist-induced down-regulation of m1 muscarinic receptors might be due to, at least in part, a decrease in receptor synthesis resulting from a reduction in the steady-state level of their mRNA. PMID- 2265700 TI - Arrestin from nucleated red blood cells binds to bovine rhodopsin in a light dependent manner. AB - Using a panel of monoclonal antibodies, it has previously been demonstrated that the cytosol of nucleated red cells (trout and turkey) contains a protein similar to arrestin, a soluble protein found so far only in the photosensitive cells and which, by binding to photoexcited rhodopsin, inhibits the phototransduction process. The role of this arrestin-like protein in non-photosensitive cells is questionable. In this report we present evidence that partially purified red blood cell arrestin (RBC arrestin) behaves functionally like bovine retinal arrestin: it binds to phosphorylated bovine rhodopsin only when this receptor has been photoactivated. Thus RBC arrestin and bovine retinal arrestin are closely related both structurally and functionally. By analogy with the function of retinal arrestin, it is proposed that RBC arrestin is involved in desensitization of membrane transport proteins and/or adrenergic receptors. PMID- 2265701 TI - Calmodulin is a potent target for new hypothalamic neuropeptides. AB - Recently, five glycopeptides with coronaro-constrictory properties were isolated from bovine hypothalamus [(1988) Neurochemistry (USSR) 7, 519-524]. Calmodulin has been recognized in our laboratory as a target protein for the neuropeptides isolated from hypothalamus. The results of indirect enzyme-linked immunosorbent assay have shown that the new hypothalamic neuropeptides antagonize with the monospecific anti-calmodulin antibody for calmodulin binding although they are not fragments of calmodulin. The inhibitory potency of the peptides is dependent on their concentration and the length of the polypeptide chain. Four out of five peptides are effective in nM concentration range. Ca2+ stimulates the binding of peptides to calmodulin; however, immunocomplex can be formed in the absence of Ca2+ as well. The effects of trifluoperazine and peptides on the calmodulin/antibody interaction are not additive, suggesting the cooperativity between the binding sites on calmodulin. Under physiological conditions the presence of the peptides could produce distinct conformers of calmodulin which may exhibit altered potency for stimulation/inhibition of target enzymes. PMID- 2265703 TI - Evidence for aggregation of endothelin 1 in water. AB - In this report it is shown by CD spectroscopy that endothelin 1, when dissolved in water, is able to present intermolecular interactions leading to formation of aggregates. Surface tension and conductivity measurements suggest that the aggregation occurs through formation of micelles with a CMC of about 2.2 x 10(-5) M. PMID- 2265702 TI - Stimulation of the receptor for melanocyte-stimulating hormone by retinoic acid. AB - Treatment of Cloudman S91 melanoma cells with retinoic acid (RA) inhibits MSH induced tyrosinase activity and melanin formation [(1990) J. Invest. Dermatol. 94, 461-464]. We report here, however, that in spite of inhibiting MSH-induced pigmentation, RA treatment caused a marked increase in MSH binding capacity for both cell surface and internal MSH binding sites. The stimulation was dose- and time-dependent and reversible, with half-maximal effects seen at 2 microM RA. Stimulation of MSH binding was seen as early as 3 h after exposure of cells to RA. Cell surface and internal binding activity increased in concert. Scatchard analysis indicated that increased MSH binding resulted from a 3-4-fold increase in the number of sites with no significant difference in their affinity for MSH. It appears that in suppressing MSH-induced melanogenesis, RA elicited a compensatory up-regulation of the MSH receptor system. PMID- 2265704 TI - Characterization of a protein that appears in the nervous system of the moth Manduca sexta coincident with neuronal death. AB - Two-dimensional gel electrophoresis was used to locate potential neuronal death related proteins in the moth Manduca sexta. Protein patterns of ganglia of pharate adult moths (taken prior to adult ecdysis) compared with protein patterns of one-day-old adults revealed reproducible changes in protein patterns. An acidic protein of approximately 40,000 Da was present in all samples from adult moths undergoing neuronal death and essentially absent from pharate adult samples. PMID- 2265705 TI - Cloning and sequence analysis of a cDNA for human glycosylasparaginase. A single gene encodes the subunits of this lysosomal amidase. PMID- 2265706 TI - Reversible ADP-ribosylation of the 78 kDa glucose-regulated protein. AB - Starvation of Mouse hepatoma cells for essential amino acids or glucose results in the mono-ADP-ribosylation of the 78 kDa glucose-regulated protein, GRP78. Here we show that the ADP-ribosylated and non-ADP-ribosylated forms of GRP78 are interconvertible during tryptophan starvation and refeeding. In addition, the ADP ribosylation of GRP78 was shown to be reversible even during nutritional stress. The overexpressed pool of non-ADP-ribosylated GRP78 synthesized during tunicamycin treatment was available for ADP-ribosylation during subsequent amino acid starvation, especially in the absence of tunicamycin. The reversible ADP ribosylation of GRP78 could be part of a metabolic control mechanism in operation during nutritional stress. PMID- 2265707 TI - The 12 kDa protein of potato virus M displays properties of a nucleic acid binding regulatory protein. AB - The 3' terminal 1.4 kb segment of potato virus M (PVM) genomic RNA was cloned and sequenced. This part of the viral genome encodes the capsid protein CP as well as a 12 kDa protein of as yet unknown function. Both proteins were expressed in bacteria and their nucleic acid-binding properties studied. The 12 kDa protein (pr12), but not the capsid protein bound single- and double-stranded nucleic acids. This property of pr12 in conjunction with a zinc finger motif located adjacent to a basic region of the 12 kDa protein suggests that it may act as a regulatory factor during virus replication. PMID- 2265708 TI - Restricted localization of the adipocyte/muscle glucose transporter species to a cell surface-derived vesicle fraction of 3T3-L1 adipocytes. Inhibited lateral mobility of integral plasma membrane proteins in newly inserted membrane areas of differentiated 3T3-L1 cells. AB - The recent demonstration of a large cell surface-derived pool of insulin sensitive glucose transporters, presumably concentrated in the microvilli of 3T3 L1 adipocytes, induced the assumption that in differentiated adipocytes, newly inserted plasma membrane areas may display restricted lateral mobility, thereby preventing diffusion of integral membrane proteins out of these areas into the adjoining plasma membrane. In order to test this assumption, the cell surface distributions of the two glucose transporter species expressed by 3T3-L1 cells were determined using specific antisera against the HepG2/erythrocyte transporter, GluT1, which is synthesized in both fibroblasts and adipocytes, and the adipocyte/muscle-specific transporter, GluT4, expressed for the first time 3 4 days after induction of adipose conversion. GluT1 was shown to be localized in the plasma membrane of both 3T3-L1 preadipocytes and adipocytes, whereas GluT4 was almost entirely restricted to the low density surface-derived vesicle (LDSV) fraction of 3T3-L1 adipocytes most likely consisting of microvilli-derived vesicles. In contrast to the minor portion of GluT4 found in the adipocyte plasma membrane fraction, equal amounts of the GluT1 protein were detected in both the plasma membrane and the LDSV fractions of adipocytes. Both transporter species were present in the microsomal and the LDSV fractions of adipocytes. The observed distribution of the two transporter species is in accordance with the postulated restriction of the lateral mobility in plasma membrane areas formed by newly inserted transgolgi vesicles of differentiated adipocytes. PMID- 2265709 TI - Inhibition of insulin secretion by interleukin-1 beta and tumour necrosis factor alpha via an L-arginine-dependent nitric oxide generating mechanism. AB - Inhibition of glucose-induced insulin secretion by interleukin-1 beta (IL-1 beta), or IL-1 beta plus tumour necrosis factor-alpha (TNF-alpha), was less marked when rat islets of Langerhans were cultured for 12 h with these cytokines in L-arginine-free medium as opposed to medium containing L-arginine (1 mM). Inhibition of secretion by IL-1 beta was further alleviated when islets were maintained in L-arginine-free medium supplemented with N-omega-nitro-L-arginine methyl ester (NAME), while synergism between IL-1 beta plus TNF-alpha was completely abolished. Tissue culture medium nitrite levels were raised in islets treated with IL-1 beta or TNF-alpha (48 h). Cytokine-stimulated nitrite production was not observed in islets cultured with NAME (1 mM). In conclusion, an L-arginine-dependent nitric oxide generating mechanism is involved in the inhibition of insulin secretion by IL-1 beta, and accounts for the phenomenon of synergism between IL-1 beta and TNF-alpha. PMID- 2265710 TI - Stereospecificity in enzymic and non-enzymic oxidation of beta-O-4 lignin model compounds. AB - The degradation of the erythro and threo isomers of the non-phenolic lignin model compound 2-(2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-1,3-propanediol was examined. Enzymic and non-enzymic oxidation of the diastereomers was performed with Trametes versicolor lignin peroxidase and cerium(IV) ammonium nitrate, respectively. Mixtures of approximately equal amounts of the diastereomers were partially degraded and subsequently analyzed with TLC and 1H-NMR. Analysis of reaction mixtures from enzymic as well as non-enzymic oxidation, revealed a preferential degradation of the threo form. Preliminary analyses of enzymic reaction mixtures of either the erythro or threo isomer suggest they yield in part different products. The observations made would have implications for the understanding of how enzymes attack lignins. They should also be taken into consideration in experiments where model compounds are being used to mimic native lignin. PMID- 2265712 TI - Surface membrane CD4 turnover in phorbol ester stimulated T-lymphocytes. Evidence of degradation and increased synthesis. AB - Down-regulation of surface membrane CD4 (smCD4) in phorbol ester stimulated T cells resulted from internalization. Internalization (T1/2 = 15 min at 50 ng PMA/ml) was followed by degradation of CD4-bound antibodies. Degradation in unstimulated T-cells was comparatively insignificant. Release of degradation products was PMA dose-dependent and could be inhibited by methylamine. Uptake and degradation continued after maximal down-regulation of surface membrane CD4, and methylamine did not inhibit reappearance of smCD4 antigens. Metabolic labelling of T-cells further showed that ongoing synthesis rather than recycling contributed to an accelerated smCD4 turnover in activated cells. PMID- 2265711 TI - Complete assignment of the 1H NMR spectrum and secondary structure of the DNA binding domain of GAL4. AB - Complete 1H NMR resonance assignments are presented for the cysteine rich region of the DNA binding domain of the yeast transcriptional activator GAL4. The protein contains short helical regions between Asp-12 and Leu-19 and between Lys 30 and Trp-36. It is clearly distinct from the C2H2 class of zinc finger protein typified by the Xenopus laevis transcription factor (TF)IIIA. We also find that the first SP(X)(X) sequence, a recently proposed DNA binding motif (residues 41 to 44), appears to be tightly packed against the metal binding domain. PMID- 2265713 TI - Gap junctional permeability is affected by cell volume changes and modulates volume regulation. AB - Isolated pancreatic acinar cell pairs became electrically uncoupled by exposure to a mild hypotonic shock. Reduction of bath osmolarity caused a delayed closure of gap junctional channels in the minute range. Dialysis of cell pairs by GTP[S] in the double whole-cell patch-clamp mode shortened the latency and shifted the hypotonically induced electrical uncoupling to lower osmolarity changes. Cellular treatment with cytochalasin B catalyzed electrical uncoupling by a hypotonic shock. In all cases, electrical uncoupling could be blocked completely by the protein kinase C (PKC) inhibitor polymyxin B. These results provide the first evidence suggesting that changes of cell volume and gap junctional permeability are correlated and that a G-protein dependent mechanism is involved. Evidence is presented that gap junctional coupling modulates volume regulation. PMID- 2265714 TI - Crystallisation and preliminary X-ray diffraction studies of cyclophilin tetrapeptide and cyclophilin-cyclosporin complexes. AB - Recombinant human cyclophilin has been co-crystallised with a number of peptides to give crystals suitable for X-ray analysis. The crystal complexes for which heavy-atom derivatives have been prepared and X-ray data collected are: cyclophilin with N-acetyl-Ala-Ala-Pro-Ala-amidomethyl-coumarin (I) which crystallises in space group P2(1)2(1)2(1) with a = 108.2, b = 123.0, c = 35.8 A, and cyclophilin with cyclosporin (II) which crystallises as tetragonal plates in space group P4(1)2(1)2 or P4(3)2(1)2 with a = b = 94.98, c = 278.55 A. PMID- 2265715 TI - Regulation of the hexaheme nitrite/nitric oxide reductase of Desulfovibrio desulfuricans, Wolinella succinogenes and Escherichia coli. A mass spectrometric study. AB - Dissimilatory nitrite reduction, carried out by hexaheme proteins, gives ammonia as the final product. Representatives of this enzyme group from 3 bacterial species can also reduce NO to either ammonia or N2O. The redox regulation of the nitrite/nitric oxide activities is discussed in the context of the denitrifying pathway. PMID- 2265716 TI - Reduction of nerve growth factor level in the brain of genetically ataxic mice (weaver, reeler). AB - By a highly sensitive enzyme immunoassay we measured the level of nerve growth factor (NGF) in the cerebellum and cerebrum of the neurologically mutant mice, weaver, reeler and Purkinje cell degeneration (PCD). A significant decrease in NGF level was observed in both cerebellum and cerebrum of weaver and reeler mutants of either sex. However, there was no such difference between normals and mutants in the case of the PCD mice. These results show that weaver and reeler mice have abnormalities of NGF synthesis and/or degradation not only in the cerebellum but also in the cerebrum. PMID- 2265717 TI - Haem binding to horse spleen ferritin. AB - Horse spleen ferritin, a spherical protein shell of 24 subunits, contains no haem when extracted. This contrasts with ferritins isolated from bacterial sources which have the capacity to bind up to 24 haem groups [(1990) FEBS Lett. 271, 141 143] via two methionine residues [(1990) Nature 341, 771]. Here it is shown that horse spleen ferritin can bind between 15 and 17 haems per 24 subunits with an apparent association constant of 2.2-3.2 x 10(4) M-1. The strength of haem binding appears to be unaffected either by the presence of the core or by the oxidation state of the haem. The demonstration of the ability of animal ferritin to bind haem strengthens the similarity between it and bacterioferritin and could have major consequences for its mechanism of action in physiological iron uptake and release processes. PMID- 2265718 TI - Evidence that the tightly bound magnesium in tubulin is associated with the N site GTP. AB - In an attempt to determine whether the tightly bound Mg2+ found in purified tubulin in associated with the N-site GTP or the E-site GDP or GTP, we removed the E-site nucleotide by several means: (i) alkaline phosphatase treatment; (ii) displacement using excess GMPPCP; and (iii) polymerizing tubulin in the presence of alkaline phosphatase and non-hydrolyzable analogues. The Mg2+ content remained equal to about 1 mol/mol tubulin under conditions where denaturation did not occur. Moreover, the Mg/GTP ratio always remained equal to 1. These results indicate that the Mg2+ is associated with the N-site GTP. PMID- 2265720 TI - Flexible scheduling and part-time work: what price do we pay? PMID- 2265719 TI - Chloroplast ribosomal protein L32 is encoded in the chloroplast genome. AB - The 50 S subunit of chloroplast ribosomes was prepared from tobacco leaves. The proteins were fractionated and the N-terminal amino acid sequence of a 14 kDa protein was determined. This sequence matches the N-terminal sequence deduced from ORF55 located between ndhF and trnL on the small single-copy region of tobacco chloroplast DNA. The deduced protein shows homology to E. coli and B. stearothermophilus L32 proteins, and it has been named as CL32 and ORF55 as rpl32. The tobacco chloroplast genome therefore contains 21 different ribosomal protein genes. PMID- 2265721 TI - Critical care in China. PMID- 2265722 TI - Life-sustaining technologies. Ordinary or extraordinary? PMID- 2265723 TI - Mentoring: nurturing the critical care nurse. AB - Mentoring is an active process that is currently receiving widespread attention in education, in the corporate world, and increasingly in health care. Job satisfaction of the critical care nurse may be related to the fulfillment of personal needs and goals. The attainment of these needs and goals ultimately will lead to increased job productivity, which in turn will promote cost effectiveness, an outcome cherished by management. Therefore, recognizing the worth of job satisfaction to the institution and the possibility that mentoring may have an effect on it among the professional staff may be a key to the future of improved health care and cost reduction in an increasingly specialized and technologic health care environment. Certainly, the nursing shortage is no longer news to the lay public or those of us engaged in the practice of nursing. In critical care that shortage is acutely apparent. Attrition of qualified critical care nurses is increasing and various solutions to the shortage have been proposed, some being met with more enthusiasm than others. A more basic solution might be to answer the question, "How can we maintain a high quality of patient care while promoting job satisfaction and instilling a sense of self-worth within the critical care nurse?" Critical care nurses need to play a pivotal role in nurturing and developing other critical care nurses as a means to retain those individuals. How can they do that effectively? Mentoring is one answer. PMID- 2265724 TI - Stunned myocardium. PMID- 2265726 TI - Assessing pain in the critically ill child. PMID- 2265725 TI - Withdrawing treatment. PMID- 2265727 TI - Teaching strategies for the transplant recipient: a review and future directions. PMID- 2265728 TI - Pulmonary contusion. PMID- 2265729 TI - Using a structured cardiopulmonary resuscitation flow sheet. PMID- 2265730 TI - Hurricane Mary--the whirling dervish. PMID- 2265731 TI - Report on The Sixth International Conference on AIDS. PMID- 2265732 TI - Women and HIV/AIDS: World AIDS Day 1990. PMID- 2265733 TI - Psychological impact of continuous subcutaneous insulin infusion pump therapy in non-selected newly diagnosed insulin dependent (type 1) diabetic children: evaluation after two years of therapy. AB - Thirty type 1 (insulin dependent) diabetic children were treated from diagnosis onwards in a random order (using a table of random permutations) with either continuous subcutaneous insulin infusion pump therapy (CSII), or with conventional injection therapy (CT). After two years of therapy psychosocial measurements were obtained of fifteen CSII children (8 boys, 7 girls; mean age: 12+/-4 years) and thirteen CT children (6 boys, 7 girls; mean age: 10+/-4 years) and their parents. Two families of the CT group refused to participate. The examination consisted of six tests (for the children: junior dutch personality test, WISC-R intelligence test, family relation test, diabetes questionnaire; for the parents: family interaction scale and assessment of acceptance scale). Parents (and pediatricians) rated CSII children higher on compliance and better on metabolic control. Acceptance of diabetes, physical and psychological condition was rated equally by parents and doctors. Except for the diabetes questionnaire, the children of the two groups scored not significantly different. The CSII group expressed significantly less physical complaints and physical restrictions. CSII children showed a tendency to score higher on recalcitrance compared with CT children. How adequate this coping of CSII children may be, is discussed. PMID- 2265734 TI - Normalization of the altered liver function tests after islet transplantation in diabetic rats. AB - The purpose of our study was to determine if streptozotocin induced diabetes (SID) in rats produces alterations in hepatic function, as described in poorly controlled diabetic patients, and if islet transplantation (islet-Tx) would subsequently ameliorate this status. Hepatocellular dysfunction was evaluated by the aspartate aminotransferase (SGOT) and the alanine aminotransferase (SGPT) activities in plasma. For the evaluation of cholestasis the plasma alkaline phosphatase (APase) activity was used. These determinations were performed in normal, SID, SID with Islet-Tx, and SID Wistar rats with sham-Tx. Also, glucose was measured in plasma samples, as well as histological studies of the liver were performed. More than 1,000 isogeneic islets (islet-Tx group) or non viable insular tissue (sham-Tx group) were transplanted via mesenteric ileal vein three weeks after SID. The results showed that SID in rats produces alterations in the hepatic function as well as in the structure of the hepatocytes, and the normalization of carbohydrate metabolism by islet transplantation restores normal hepatic function and morphology. PMID- 2265736 TI - [Diabetes in the Belgian province of Luxembourg: frequency, importance of the oral glucose tolerance test and a modestly increased fasting blood glucose]. AB - A sample of 1949 subjects aged 35-64 years has been studied in the Belgian Province of Luxembourg according with the MONICA project (MONItoring of Trends and Determinants in CArdiovascular Diseases) elaborated by the World Health Organization. Among the data collected, were a fasting glycaemia and a glycaemia at the second hour of a 75 grams oral glucose load. Analysis of these two parameters has allowed to divide the individuals of the study into: 4.1% of diabetic subjects which half of them being unknown, 5.2% of subjects presenting an impaired glucose tolerance, 3.4% of subjects with an early reactive hypoglycaemia and 87.3% of normoglycaemic subjects. The measurement of the fasting glycaemia alone has allowed to display 15 glucidic abnormalities (that is to say 0.8%) whereas the complementary realization of the oral glucose tolerance test has disclosed about 10% of additional abnormalities. The fact to consider a borderline fasting glycaemia (included between 110 and 140 mg/dl on venous plasma) result in a greater probability to find an abnormal blood glucose value at the second hour of the oral glucose tolerance test. PMID- 2265735 TI - Probability of remission in individual in early adult insulin dependent diabetic patients. Results from the Cyclosporine Diabetes French Study Group. AB - The aim of this study was to determine which candidates were suitable for immunotherapy among adult insulin dependent diabetic patients of recent onset. A statistical analysis was performed using the results of a multicentre randomized trial of cyclosporine versus placebo after nine months of treatment. When the baseline characteristics of the patients in remission were compared with those not in remission, there was no difference observed either in initial residual beta-cell function (glucagon stimulated C-peptide level), or in immunological markers (T4 and T8 lymphocytes counts, Interleukin 2). The parameters showing the most difference were, in addition to treatment group, the duration of diabetes symptoms and body mass index at inclusion, and the HLA-DR phenotype. This was confirmed using a logistic regression analysis, in which these variables were found to be significantly related to remission. The probability of remission in each individual patient was then calculated using these variables in the mathematical function provided by the logistic model. Ninety eight out of 110 patients were correctly classified using this method. In addition, it must be noted that only subjects adequately treated by cyclosporine were still in complete remission after a one year follow-up. Conversely, it appeared that immunosuppression in subjects having a predicted probability of remission lower than 0.35 using the mathematical function, and being non-DR3, non-DR4 has to be avoided. These results will be useful in optimizing the recruitment of patients in on-going or future trials of immunotherapy in early diabetes. PMID- 2265737 TI - Evidence for a possible role of oxygen free radicals in the abnormal functional arterial vasomotion in insulin dependent diabetes. AB - A functional arterial spasm, revealed by reduced post-ischemic response, is present in diabetic subjects with no overt evidence of vascular damage. The administration of three different antioxidant agents, vitamin C, thiopronine and glutathione, produces an increase of basal blood flow in both diabetic and normal subjects, and ameliorates significantly the vascular functional response in diabetes. These data suggest that free radicals may play a role in the regulation of arterial resistance in humans, and that a de-regulation of their action may be involved in the development of arterial dysfunction in diabetes. PMID- 2265739 TI - [Blood cholesterol, diet and coronary risk: is the French population protected or threatened? Report of a consensus conference]. PMID- 2265738 TI - Impaired insulin-mediated erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose diposal in aged non-diabetic obese patients. AB - Basal erythrocyte magnesium levels were significantly lower in obese than lean subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both groups of subjects. However, even in the presence of 100 mU/l, the erythrocyte magnesium content of obese patients was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when the red cells of obese were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in obese patients results essentially from a post-receptor defect. In obese patients, net increase in erythrocyte magnesium levels (calculated as the difference between basal and 100 mU/l insulin-induced erythrocyte magnesium levels) was negatively correlated with basal plasma insulin levels (r = 0.79 p less than 0.01), and with body mass index (r = 0.81 p less than 0.01) while it was positively correlated with the glucose disappearance rate after glucose load (r = 0.67 p less than 0.05) and glucose metabolic clearance rate (r = 0.71 p less than 0.01). These results demonstrate that insulin-induced erythrocyte magnesium accumulation is impaired in patients with obesity and that such defect is correlated to impaired -- mediated glucosal disposal in the patients. PMID- 2265740 TI - Withholding tax liability: buyer beware. PMID- 2265741 TI - Early engineering planning for health care facilities. PMID- 2265742 TI - Designing a multilevel care facility for seniors. PMID- 2265743 TI - Earthquake! Is your hospital prepared? PMID- 2265744 TI - Nurse executive job satisfaction and CEO effectiveness. PMID- 2265745 TI - Measuring effectiveness in infection control. PMID- 2265746 TI - Developing RM standards. PMID- 2265747 TI - What about smaller hospitals? PMID- 2265748 TI - Thiobacillus ferrooxidans mer operon: sequence analysis of the promoter and adjacent genes. AB - The merA upstream nucleotide (nt) sequence (1378 bp) of the Hg2(+)-resistance encoding gene system (mer) in Thiobacillus ferrooxidans, was determined. The region contains two open reading frames: unidentified reading frame 1 (URF1) and merC. URF1 has 63-73% homology with those of Tn501, R100 and pDU1358, although the corresponding product has not yet been identified. Thiobacillus merC had 61% and 55% homology with R100 merC at the nt and amino acid (aa) sequence levels, respectively, and its product, consisting of 143 aa, was highly hydrophobic. No sequence homologous to merR, merT. merP or merD of R100 were observed on either strand. Within the 70-100-bp sequence upstream from the merC start codon. there was a sequence highly homologous to the promoter of merT of other Gram- mer systems. From primer extension and Northern-blot analyses, it became clear that merC and merA were co-transcribed from this putative transcription start point. The mer transcript in T. ferrooxidans was only detected in Hg2(+)-induced cells. Therefore, it was concluded that the T. ferrooxidans mer system is an inducible operon. PMID- 2265749 TI - A library of 3342 useful nonamer primers for genome sequencing. AB - Primer-directed sequencing, of double-stranded large recombinant DNA molecules, has not been accepted because of the delay and expenses involved in the synthesis of oligodeoxyribonucleotide primers. A potential solution to this problem was proposed by Studier [Proc. Natl. Acad. Sci. USA 86 (1989) 6917-6921] for using a library of short oligomer primers. Szybalski [Gene 90 (1990) 177-178] has made a complementary proposal using ligated hexamers to reduce the number of oligomers needed. We have used a set of rules for a computer-aided selection of a library consisting of 3342 specific nonamers. The effectiveness of this library of nonamers to sequence specific genes was studied using human sequences available in GenBank. PMID- 2265750 TI - A general method for rapid site-directed mutagenesis using the polymerase chain reaction. AB - We have developed a general and rapid method for site-directed mutagenesis using primed amplification by the polymerase chain reaction. Starting from a double stranded DNA template, this method requires only one single specific mutagenic primer and two universal sequencing primers flanking the region to be mutated further upstream and downstream, respectively. To test the method, two different mutants of the RNase T1-encoding gene have been constructed by this technique. Twelve sequenced mutant clones all showed the expected mutations without any wild type background. PMID- 2265751 TI - Nucleotide sequence of the F plasmid gene, traC, and identification of its product. AB - The traC gene of the F plasmid tra operon is required for the assembly of mature F-pilin subunits into extended F pili. The nucleotide sequence of traC was determined with a determined with a deduced coding region of 875 amino acids (aa) and 99066 Da. The traC1044 mutant allele, which allows filamentous phage infection in the absence of piliation, contains a C-to-T transition leading to an Arg----Cys substitution. Confirmation of the translational start came from the direct N-terminal aa sequencing of a TraC-alkaline phosphatase fusion protein. PMID- 2265752 TI - HU-1 mutants of Escherichia coli deficient in DNA binding. AB - We constructed four mutants of the Escherichia coli hupB gene, encoding HU-1 protein, by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The HupBR45 protein contained alterations of Arg58----Gly and Arg61----Gly, and the HupBF3, HupBK2 and HupBA1 proteins contained Phe47----Thr, Lys37----Gln and Ala30----Asp alterations, respectively. HupBF3 and HupBR45 were unable to maintain normal cell growth in a hupA-hupB-himA triple mutant at 42 degrees C, mini-F or RSF1010 proliferation, or Mu phage development in a hupA-hupB double mutant, whereas HupBA1 and HupBK2 supported these cellular activities. DNA-affinity column chromatography showed that the HupBF3 and HupBR45 had reduced affinities to DNA. These observations indicate that two highly conserved Arg residues in the arm structure of the C-terminal half of the HU-1 molecule and a Phe residue in the short beta-sheet connecting the two halves of the molecule are important for the DNA-binding ability and biological functions of this protein. PMID- 2265753 TI - Nucleotide sequence of the replication region from the Mycobacterium-Escherichia coli shuttle vector pEP2. AB - The replication region derived from the Corynebacterium diphtheriae-Escherichia coli plasmid pNG2 was sequenced. This 1.85-kb segment contains a single origin of DNA replication, one major open reading frame and shares no sequence homology with previously described plasmids. PMID- 2265754 TI - The superoxide dismutase-encoding gene of the obligately anaerobic bacterium Bacteroides gingivalis. AB - The gene (sod) encoding the superoxide dismutase (SOD) of the obligately anaerobic bacterium Bacteroides gingivalis was cloned. The amino acid (aa) sequence of the SOD, deduced from the nucleotide sequence of the sod gene, basically resembled that of known Fe-SODs. However, the aa sequence of the B. gingivalis SOD was found to be intermediate between those of Fe-SOD and Mn-SOD in a limited region around the putative second ligand, where major differences between the aa sequences of Fe-SOD and Mn-SOD are known to exist. PMID- 2265755 TI - High efficiency transformation of Escherichia coli with plasmids. AB - We have re-evaluated the conditions for preparing competent Escherichia coli cells and established a simple and efficient method (SEM) for plasmid transfection. Cells (DH5, JM109 and HB101) prepared by SEM are extremely competent for transformation (1-3 x 10(9) cfu/microgram of pBR322 DNA), and can be stored in liquid nitrogen for at least 40 days without loss of competence. Unlike electroporation, transformation using these competent cells is affected minimally by salts in DNA preparation. These competent cells are particularly useful for construction of high-complexity cDNA libraries with a minimum expenditure of mRNA. PMID- 2265756 TI - Genomic replacement in Escherichia coli K-12 using covalently closed circular plasmid DNA. AB - A number of gene replacements at different loci were constructed using covalently closed circular (ccc) plasmid DNA in the recB21 recC22 sbcB15 sbcC201 mutant of Escherichia coli (JC7623). Selected constructs representing deletions and insertion mutations formed from double-crossover events involving the ccc plasmid molecules and the genome were confirmed by Southern blots, and the frequency of double-crossover events was evaluated. It is reported that such mutants may be constructed without linearizing plasmid DNA, as described previously. PMID- 2265757 TI - In vivo genetic engineering: homologous recombination as a tool for plasmid construction. AB - This paper describes a novel method for creating exact DNA fusions between any two points in a plasmid carried in Bacillus subtilis. It exploits the homologous in vivo recombination between directly repeated sequences that can be established by insertion of a synthetic oligodeoxyribonucleotide. The method was used to enhance the productivity in B. subtilis of a cloned alpha-amylase (Amy)-encoding gene originating from Bacillus stearothermophilus. Thus, an exact fusion between nucleotide sequences encoding the expression signals, including the signal peptide, of a Bacillus licheniformis Amy-encoding gene and the mature Amy of B. stearothermophilus, was created. The resulting hybrid translational product was processed correctly in B. subtilis during secretion, giving rise to an Amy identical to the mature Amy secreted by B. stearothermophilus. PMID- 2265758 TI - The virD genes from the vir region of the Ti plasmid: T-region border dependent processing steps in different rec mutants of Escherichia coli. AB - We evaluated the substrate requirements for virD-mediated T-circle formation in an in vivo binary test system in Escherichia coli. Two copies of the 25-bp sequence which defines the right border of the T-DNA (transferred DNA) are sufficient, and the right and the left copy of the border are equivalent in function in this system. Experiments with different rec mutants show that the occurrence and frequency of circular double-stranded and single-stranded T-DNA equivalents strongly depend on rec functions of the host. These results are discussed in the context of processing of the tumor-inducing Ti plasmid preceding the T-DNA transfer from agrobacteria to plants. PMID- 2265759 TI - Correct insertion of a simple eukaryotic plasma-membrane protein into the cytoplasmic membrane of Escherichia coli. AB - A genetic system for directly synthesizing eukaryotic membrane proteins in Escherichia coli and assessing their ability to insert into the bacterial cytoplasmic membrane is described. The components of this system are the direct expression vector, pYZ4, and the mature beta-lactamase (BlaM) cassette plasmid, pYZ5, that can be used to generate translational fusions of BlaM to any synthesized membrane protein. The beta-subunit of sheep-kidney Na,K-ATPase (beta NKA), a class-II plasma membrane protein, was synthesized in E. coli using pYZ4, and BlaM was fused to a normally extracellular portion of it. The fusion protein conferred ampicillin resistance on individual host cells, indicating that the BlaM portion had been translocated to the bacterial periplasm, and that, by inference, the eukaryotic plasma-membrane protein can insert into the bacterial cytoplasmic membrane. A series of 31 beta NKA::BlaM fusion proteins was isolated and characterised to map the topology of the eukaryotic plasma membrane protein with respect to the bacterial cytoplasmic membrane. This analysis revealed that the organisation of the beta NKA in the E. coli cytoplasmic membrane was indistinguishable from that in its native plasma membrane. PMID- 2265760 TI - Analysis of the tsx gene, which encodes a nucleoside-specific channel-forming protein (Tsx) in the outer membrane of Escherichia coli. AB - The tsx gene of Escherichia coli encodes an outer membrane protein, Tsx, which constitutes the receptor for colicin K and bacteriophage T6, and functions as a substrate-specific channel for nucleosides and deoxynucleosides. The mini-Mu element pEG5005 was used to prepare a gene bank in vivo, and this bank was used to identify T6-sensitive strains carrying the cloned tsx gene. Subcloning of the tsx gene into the multicopy plasmid, pBR322, resulted in a strong overproduction of Tsx. The sequence of a 1477-bp DNA segment containing tsx and its flanking regions was determined. An open reading frame (ORF) was found which was followed by a pair of repetitive extragenic palindromic sequences. This ORF translated into a protein of 294 amino acids (aa), the first 22 aa of which showed the characteristic features of a bacterial signal sequence peptide. The putative mature form of Tsx is composed of 272 aa with a calculated Mr of 31418. The aa sequence of Tsx shows an even distribution of charged residues (52 aa) and lacks extensive hydrophobic stretches. No significant homologies of Tsx to the channel forming proteins OmpC, OmpF, PhoE and LamB from the E. coli outer membrane were detected. Using nuclease S1, we identified two transcription start points for the tsx mRNA which were separated by approx. 150 bp. Genetic data suggest that the synthesis of the larger mRNA species is directed by a weak promoter (P1) that is controlled by the DeoR repressor, whereas the smaller mRNA species is directed by the main promoter P2, which is negatively controlled by the CytR repressor and positively affected by the cyclic AMP/catabolite activator protein complex. PMID- 2265761 TI - Cloning, sequencing and characterization of the [NiFe]hydrogenase-encoding structural genes (hoxK and hoxG) from Azotobacter vinelandii. AB - The Azotobacter vinelandii [NiFe]hydrogenase-encoding structural genes were isolated from an A. vinelandii genomic cosmid library. Nucleotide (nt) sequence analysis showed that the two genes, hoxK and hoxG, which encode the small and large subunits of the enzyme, respectively, form part of an operon that contains at least one other gene. The hoxK gene encodes a polypeptide of 358 amino acids (aa) (39,209 Da). The deduced aa sequence encodes a possible 45-aa N-terminus extension, not present in the purified A. vinelandii hydrogenase small subunit, which could be a cellular targeting sequence. The hoxG gene is downstream form, and overlaps hoxK by 4 nt and encodes a 602-aa polypeptide of 66,803 Da. The hoxK and hoxG gene products display homology to aa sequences of hydrogenase small and large subunits, respectively, from other organisms. The hoxG gene lies 16 nt upstream from a third open reading frame which could encode a 27,729-Da (240-aa) hydrophobic polypeptide containing 53% nonpolar and 11% aromatic aa. The significance of this possible third gene is not known at present. PMID- 2265762 TI - Isolation and characterization of levansucrase-encoding gene from Bacillus amyloliquefaciens. AB - The gene encoding levansucrase (LVS) from Bacillus amyloliquefaciens (sacB[BamP]) was isolated, sequenced and expressed in Bacillus subtilis. Analysis of the nucleotide sequence of sacB[BamP] reveals extensive homology with that of the B. subtilis LVS-encoding gene in the promoter and coding region. The sacB[BamP] gene cloned in a multicopy plasmid is induced by sucrose in B. subtilis. PMID- 2265763 TI - Characterization of the cos sites of bacteriophages P2 and P4. AB - A 641-bp cos-containing P2 DNA fragment was sequenced and compared to the P4 cos region. Alignment of the P2 and P4 cos regions shows a homologous region of 55 bp that has only three mismatches and contains a completely conserved region of dyad symmetry. A number of P4- and P2-derived cosmids were tested in an in vivo transduction assay in order to determine the minimal cos region required for packaging. These experiments show that the common region of 55 bp is sufficient for transduction with low frequency, but that a 125-bp cos-containing fragment contains all the information for transduction with optimal frequency. PMID- 2265764 TI - Subretinal neovascular membranes associated with chronic membranoproliferative glomerulonephritis type II. AB - Subretinal neovascular membranes were observed in three patients with chronic membranoproliferative glomerulonephritis type II (dense deposit disease). The first signs of glomerulonephritis occurred at respective ages of 13, 10 and 10 years; subretinal neovascular membranes were noted at respective ages of 25, 32 and 32 years. All patients had bilateral, widespread retinal pigment epithelial abnormalities. Our findings indicate that subretinal neovascularization is a complication of dense deposit disease. In one patient, the early recognition and laser treatment of an extrafoveal subretinal neovascular membrane prevented further loss of vision. PMID- 2265765 TI - Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. AB - The effect of 18 months' inhibition of angiotensin-converting enzyme by captopril on the leakage of fluorescein through the blood-retina barrier was examined in a prospective, randomized control study of 20 normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. After 18 months, 15 patients remained in the study. Fluorescein leakage remained nearly unchanged in the captopril-treated group, being 4.1 +/- 4.1 (mean +/- SD) x 10(-7) cm/s at baseline and 4.2 +/- 4.1 x 10(-7) cm/s after 18 months' treatment. The permeability increased significantly (P less than 0.01) from 3.3 +/- 2.2 x 10(-7) cm/s to 5.6 +/- 3.5 x 10(-7) cm/s at 18 months in the control group. Arterial blood pressure was nearly constant in both groups throughout the study. The results indicate that angiotensin-converting enzyme inhibition with captopril can arrest or delay a progressive breakdown of the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. PMID- 2265766 TI - Optic disc topography and short-term increase in intraocular pressure. AB - Intraocular pressure is intra- and interindividually inconstant. It is influenced by numerous ocular and general factors. We evaluated the question as to whether a short-term increase in intraocular pressure might change the two-dimensional topography of the optic nerve head. Optic disc photographs of 63 glaucomatous eyes in 33 Caucasian patients and 39 normal eyes in 22 subjects were taken at a baseline intraocular pressure of less than 20 mm Hg and at 1 and 8 s after pressure elevations of 10 and 20 mm Hg. No significant differences in the size and form of the optic disc, optic cup, neuroretinal rim, peripapillary scleral ring or parapapillary chorioretinal atrophy were found. The retinal vessels mostly reacted to the intraocular pressure elevation by an initial decrease and subsequent re-increase in their diameter; this change was significant (P less than 0.05) for the pressure elevation of 20 mm Hg. We conclude that the two dimensional optic disc topography is not significantly changed by a short-term increase in intraocular pressure. PMID- 2265767 TI - Lectin-binding sites in the anterior segment of the human eye. AB - The anterior segment of the human eye was screened for differences in the lectin binding patterns of Con A, PNA, GS-I, WGA, SBA, DBA, and UEA-I to enable cell typing for cell-culture purposes. An immunohistochemical technique combining an indirect antibody-lectin method with the avidin-biotin system was used. Con A and WGA were bound by all cells except the conjunctival goblet cells. UEA-I was exclusively bound by both vascular endothelial cells and some corneal and conjunctival epithelial cells. The binding of GS-I, PNA, SBA, and DBA showed an uneven pattern and differed among the cases investigated. The reasons for these differences are not clear. Our results indicate that the usefulness of lectins for cell-typing purposes is restricted and must be determined for every case. PMID- 2265768 TI - Evaluation of polyvinyl alcohol hydrogel as a soft contact lens material. AB - We prepared a transparent polyvinyl alcohol (PVA) hydrogel from a PVA solution in a mixed solvent consisting of water and a water-miscible organic solvent by cooling. The physical properties of the hydrogel were evaluated in various mixed solvents and compared with those of commercially available soft contact lens materials, such as polyhydroxyethyl methacrylate (PHEMA) and copolymers of methylmethycrylate (MMA) and N-vinyl pyrrolidone (N-VP). The PVA hydrogel showed higher tensile strength and elongation before breaking than did the other materials. Also, the PVA hydrogel was comparable in its high water content and its oxygen permeability with the MMA/VP copolymers. The protein adsorption of the PVA hydrogel was much lower than that of the other materials. Soft contact lenses of PVA hydrogel were applied to rabbit eyes for 12 weeks. The effects of the lenses on the cornea were studied by biomicroscopy, ultrasonic pachymetry, and histopathologic examination. No abnormal findings were noted, suggesting that the PVA hydrogel may be promising as a new material for use in soft contact lenses. PMID- 2265769 TI - Measurements of antifungal levels in corneal tissue: a simplified bioassay for amphotericin B. AB - Measuring precise antifungal levels in the cornea with broth-dilution bioassays is difficult, as standard techniques involving visual determination of endpoints are hindered by corneal debris. To increase the precision of the measurement, we modified the sample preparation for bioassay of rabbit corneas treated with subconjunctival amphotericin B. Endpoint determination and variance were compared for a freshly thawed corneal suspension and the supernatant after 24 h equilibration; bioassay of the corneal suspension after 24 h equilibration served as an additional control. All endpoints were read visually in a masked fashion and were verified by culture. The three methods gave comparable endpoint values with equivalent degrees of variance. Amphotericin B levels were consistent by both visual and culture determination; however, endpoints were clearly visible and easier to read for the supernatant. Visual determination of the endpoints for the supernatant following 24 h equilibration simplified and ensured the precision of the bioassay technique. PMID- 2265770 TI - Alterations in rabbit vitreal fine structure following C3F8 injection. AB - This study examines the morphological and histochemical changes in the cortical vitreous of 36 rabbit eyes following C3F8 intravitreal gas injection. Eyes were examined by light microscopy (LM) using a modified cryofixation and cryosectioning technique that prevented the loss of soluble tissue moieties and permitted collagen and proteoglycan histochemistry as well as enzyme digestion with hyaluronidase. LM and scanning electron microscopy (SEM) of cryosectioned normal eyes revealed an elaborate fibrillar matrix extending 100-190 microns from the basal lamina of the retina into the vitreous proper, which seemed to be composed of collagen fibrils intimately associated or wrapped in proteoglycan. Following the full expansion of the C3F8 gas bubble in the vitreous, the cortical fibrillar meshwork was absent from the retinal surface and a dense, collagenous material accumulated in the anterior vitreous, especially between the ciliary processes and over the posterior face of the lens. At 41 days postinjection, the fibrillar matrix was reforming and the vitreal cavity was filled with fluid and numerous fibrillar-mucinous islands. These islands did not form sheets or membranes, nor did they attach to either the posterior or the anterior retinal surface. The cortical fibrillar meshwork had reformed at 61 days' recovery; however, the condensed fibrillar material against the lens and filling the spaces between the ciliary processes had not resorbed. Neither shearing of the cortical gel or fibrillar matrix nor congestion of the anterior vitreous was observed in eyes only partially filled with gas. PMID- 2265771 TI - Evaluation of radiation therapy for experimental proliferative vitreoretinopathy in rabbits. AB - We evaluated effects of radiation therapy on experimental proliferative vitreoretinopathy (PVR) induced in rabbits by double gas compression of the vitreous followed by homologous dermal-skin fibroblast injection. Electrons were irradiated in two rabbit groups. Group A animals (20 eyes) received 1000 cGy of irradiation immediately after cell injection; group B rabbits (9 eyes), which showed pucker formation 7 days after cell injection, were irradiated on that day at the same dose as was given to group A rabbit. Control animals (14 eyes) were not irradiated. The incidences of traction retinal detachment on day 28 were: control, 86%; group A, 10%; and group B, 22%. There were statistically significant differences between control and group A values and between control and group B values. No significant difference was found between group A and group B. Irradiation of 1000 cGy did not alter the histological picture of experimental PVR. The results showed that radiation suppressed the development of PVR when applied not only immediately after cell injection but also during pucker stages. PMID- 2265772 TI - Experimental study on the fractionation schedule for proton irradiation of uveal melanoma. AB - Greene melanoma in the anterior chamber of rabbits was irradiated by protons to find the isoeffect curve for proton irradiation fractionated into one, two, three or four doses. The isoeffect curve for tumor tissue remained constant between one and three-dose fractionations and rose with four-dose fractionation. The isoeffect curve for normal tissue approximately followed the Ellis equation. Therefore, the optimal irradiation schedule should be in the range of three fractions because this best spares normal tissue while delivering a tumoricidal dose to the lesion. The relative reduction of the total dose from four- to one dose fractions of intraoperative irradiation should be 20%. PMID- 2265773 TI - Anterior capsule-supported intraocular lens. A new lens for small-incision surgery and for sealing the capsular opening. AB - A new intraocular lens made of PMMA and fixed in the anterior capsular opening is introduced. The lens diameter is 4 mm and the lens has no haptics in the conventional sense but is finely grooved around the circumference edge. The lens is inserted into the anterior capsule via a very small-diameter opening created by mini-circular capsulorhexis. The anterior capsular opening, with a round, smooth-edged margin, avoids stress concentration and, therefore, the capsule does not easily tear. This opening catches the lens and chokes it along the grooved edge. In animal experiments, firm fixation was obtained. This lens may be adequate for small-incision surgery, and in the future it may be used to prevent leakage of filling material during refilling of the lens, since it acts as a part of the anterior capsule and seals the capsular opening completely. PMID- 2265774 TI - Perfluorocarbon gases in the suprachoroidal space of rabbit eyes. AB - Four perfluorocarbon gases were injected into the suprachoroidal space of rabbit eyes. Temporary, expanding choroidal detachments were observed in all cases. Depending on the amount of gas injected (0.1 or 0.2 cc, respectively), they lasted 1 or 2 days in the case of perfluoromethane, 4 or 5 days with perfluoroethane, 6 or 8 days with perfluoropropane, and 9 or 11 days with perfluoro-N-butane. Due to its longevity, perfluoro-N-butane appeared to be the most suitable gas for temporary "buckling" of the suprachoroidal space in rabbit eyes. PMID- 2265775 TI - Appraisal of gut lavage in the study of intestinal humoral immunity. AB - Direct investigation of intestinal humoral immunity requires collection of intestinal secretions or mucosal biopsy specimens, or both. A non-invasive technique of gut lavage, with a polyethyleneglycol electrolyte lavage solution as a means of collecting intestinal secretions for immunoglobulin and antibody studies, was evaluated. Fifty patients were studied--25 immunologically normal patients or volunteers, 15 patients with untreated coeliac disease, and 10 patients with active Crohn's disease. Protease inhibitors were added promptly to samples to prevent proteolysis of immunoglobulin content. Treated lavage samples were assayed by enzyme linked immunosorbent assay for immunoglobulin and antibody content. Studies of serial lavage specimens showed that early, faecally contaminated specimens contained negligible quantities of immunoglobulin, but once the specimens became clear a steady state was reached, with little variation in immunoglobulin content between serial specimens and with a uniform dilution (around 20%) of the ingested polyethyleneglycol. Gut lavage fluid IgA was predominantly secretory, comprising 92%, 81.6%, and 76.7% respectively of the total IgA gut lavage fluid content in the control, coeliac, and Crohn's groups. High values of total IgM and IgA and IgM antigliadin antibodies were detected in the coeliac group, and high values of IgG in the Crohn's disease group. This method of gut lavage is not only an effective bowel cleanser, but also a noninvasive means of obtaining intestinal secretions for the study of humoral immunity in gastrointestinal disease. PMID- 2265776 TI - Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease. AB - We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component. The results were compared to the number of Ig-containing plasma cells in the test segment. There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects. The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria. In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate. The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid. Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease. Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum. This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease. PMID- 2265777 TI - Inflammatory bowel disease and tobacco smoke--a case-control study. AB - A case-control study was carried out in Stockholm, Sweden between 1984 and 1987 to evaluate the association of cigarette smoking and exposure to environmental tobacco smoke during childhood and the subsequent development of inflammatory bowel disease. Information on smoking was obtained by a postal questionnaire. The relative risk of Crohn's disease in current smokers compared with those who had never smoked was 1.33 (95% confidence limits 0.7; 2.6) in men and 4.99 (2.7; 9.2) in women; the corresponding results for ulcerative colitis were 0.96 (0.5; 1.8) and 0.72 (0.4; 1.4). The relative risk of ulcerative colitis in recent exsmokers compared with those who had never smoked was 2.18 (0.9; 5.0). Furthermore, an increase in the risk of Crohn's disease was found in those who were exposed to environmental tobacco smoke during childhood, the relative risk being 1.50 (1.0; 2.3). The corresponding relative risk of ulcerative colitis was 0.98 (0.6; 1.5). PMID- 2265778 TI - Rectal mucosal dysplasia in Crohn's disease. AB - Serial sections of 812 rectal biopsy specimens from 356 Crohn's disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn's disease who did not have dysplasia on rectal biopsy specimen. PMID- 2265779 TI - Mortality and causes of death in Crohn's disease. Review of 50 years' experience in Leiden University Hospital. AB - Six hundred and seventy one patients (52.5% women) with Crohn's disease seen at Leiden University Hospital between 1934 and 1984 were identified. Follow up was 98.2% complete. Sixty four (9.7%) of the 659 patients died. The cause of death was related to Crohn's disease in 34 patients, probably related to the disease in four, and unrelated, from incidental causes, in 25. The cause of death could not be identified in one patient. There was a significant decrease of deaths related to the disease after 1973. Causes of death such as amyloidosis and malnutrition have disappeared and postoperative deaths have decreased. The standardised mortality ratio showed an excess mortality of 2.23 for all patients. It was higher for women (3.30) than for men (1.76). A comparison of two recent 10 year periods showed a significant decrease in standardised mortality ratio in men but not in women. Patients whose disease started before the age of 20 years had an excess mortality compared with older patients. This study supports the view that the prognosis of Crohn's disease has improved in general but high quality medical and surgical management is important particularly for younger patients. PMID- 2265780 TI - Short chain fatty acids dilate isolated human colonic resistance arteries. AB - Colonic biopsy specimens were obtained from patients undergoing surgery for carcinoma of the rectum. Colonic resistance arteries (internal diameter 178-345 microns) were dissected out under the microscope and mounted in a microvascular myograph capable of measuring isometric tension development. Experiments were designed to test compounds trophic to the gastrointestinal tract--namely, glutamine and the three short chain fatty acids, acetic, propionic, and butyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM neither constricted nor dilated the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) dilatation of resistance arteries preconstricted with 50 mM K+, and this relaxant effect was unaffected by removal of the endothelium, presence of indomethacin, and preconstriction with vasopressin. These data suggest that the trophic effect of glutamine on intestinal mucosa cannot be explained through actions of this compound on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acids on resistance arteries in vitro suggests that these compounds may be able to improve the colonic microcirculation in vivo, thereby providing an explanation for their trophic effect on intestinal mucosa. PMID- 2265781 TI - Efficacy of biofeedback training in improving faecal incontinence and anorectal physiologic function. AB - The efficacy of biofeedback treatment on faecal incontinence and anorectal function was evaluated in eight patients with faecal incontinence treated with biofeedback training and medical therapy. Outcome and anorectal function were compared with nine faecal incontinent patients who received medical therapy alone. Three month follow up showed that 50% of patients in the biofeedback plus conventional treatment group and 56% of those treated conventionally only had improved. One year follow up showed that 13% in the biofeedback group were free of soiling and an additional 25% had improved. The results were similar in the conventionally treated group--11% were free of soiling and an additional 44% improved. Anal pressures at rest and squeeze, the rectal distension volume that induced sustained inhibition of both the external and internal anal sphincter, and continence to rectally infused saline were significantly reduced in both groups of patients compared with controls (p less than 0.05). Biofeedback treatment had no effect on these abnormal anorectal functions in either patients who improved or those who did not. The improvement in faecal incontinence was probably due to medical intervention or regression of symptoms with time, or both, and not the result of biofeedback training. PMID- 2265782 TI - Effects of lactulose and lactitol on protein digestion and metabolism in conventional and germ free animal models: relevance of the results to their use in the treatment of portosystemic encephalopathy. AB - Protein digestion and metabolism have been studied in laboratory rats and miniature pigs to investigate the mechanisms of action of lactulose and lactitol when used in the treatment of patients with portosystemic encephalopathy. Lactulose (beta-D-galactopyranosyl-(1----4)-beta-D-fructofuranose) and lactitol (beta-D-galactopyranosyl-(1----4)-D-glucitol) increased the excretion of nitrogenous material in the faeces and decreased nitrogen excretion in the urine in a similar degree to that reported for human patients. In studies with germ free rats given lactulose no such effect was observed, suggesting that, for lactulose at least, these effects are mediated by the gut flora. Measurement of the alpha-, epsilon-diaminopimelic acid content of the faeces confirmed that the enhancement of faecal nitrogen was due to an increased contribution from bacteria. The similarity in the results for lactulose and lactitol suggests that, from the perspective of protein metabolism, lactitol acts in a similar way to lactulose in the treatment of portosystemic encephalopathy. PMID- 2265783 TI - Comparison of gall bladder bile and endoscopically obtained duodenal bile. AB - In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic. The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001). Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples. The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples. Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001). For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects. Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile. The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis. PMID- 2265784 TI - Ethanol in pancreatic juice after oral and intravenous administration. AB - Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol. PMID- 2265785 TI - Strongyloides stercoralis associated with a bleeding gastric ulcer. AB - Infection with the helminthic parasite, Strongyloides stercoralis, is usually acquired by skin invasion (or occasionally via ingestion of larvae). After transformation to the adult form, the parasite preferentially localises in the small intestine, especially in the duodenal and jejunal part. A remarkable feature of Strongyloides is its property of endogenous reinfection. In the case of an immunocompromised host a massive infection, called hyperinfections Strongyloides, may occur. Numerous gastrointestinal complications of strongyloides infections, sometimes with a lethal outcome, have been reported. The intestinal manifestations are usually limited to the small bowel, and rarely involve the stomach. We report a patient with complicated strongyloides infection of the stomach. PMID- 2265787 TI - Prediction of severity of acute pancreatitis. PMID- 2265786 TI - Isolated lipase and colipase deficiency in two brothers. AB - Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers. PMID- 2265788 TI - Effects of albumin infusion in cirrhotic patients. PMID- 2265789 TI - Reproducibility of oesophageal pH monitoring. PMID- 2265790 TI - Elimination of high titre HIV from fibreoptic endoscopes. PMID- 2265791 TI - Systemic chemotherapy for Helicobacter pylori eradication? PMID- 2265792 TI - Diabetes and cholelithiasis. PMID- 2265793 TI - Use of elemental diets in the treatment of Crohn's disease by gastroenterologists. PMID- 2265794 TI - Vancomycin in resistant hepatic encephalopathy. PMID- 2265795 TI - Maternal and fetal levels of a novel polypeptide, endothelin: evidence for release during pregnancy and delivery. AB - The occurrence of endothelin (ET), a recently discovered polypeptide with potent vasoconstrictor properties, was studied in maternal and umbilical blood and amniotic fluid. The level of ET-like immunoreactivity (ET-LI) in maternal plasma was in most cases below the detection limit of the radioimunoassay, i.e. less than 2 pmol/l. The median concentration of ET-LI in the umbilical artery and vein before the initiation of breathing was 14.9 and 10.9 pmol/l, respectively. When sampling was performed after fetal breathing had begun, the arterial concentration increased to 93.7 pmol/l. Labor was not associated with increased concentrations of ET-LI, however, since neonates delivered by elective cesarean section had similar ET-LI in blood and amniotic fluid as after vaginal delivery. An approximately fivefold increase in the amniotic fluid ET-LI was seen at term as compared to early mid-trimester values. Reversed phase HPLC characterization revealed that the observed ET-LI mainly corresponded to ET-1. It is suggested that ET-1 may contribute to the fetal hemodynamic changes, e.g., closure of the umbilical vessels occurring at delivery. PMID- 2265796 TI - Changes of relaxin concentrations determined by immunodensitometry in ovaries of NMRI mice during pregnancy. AB - Relaxin has been localized in corpora lutea (CL) of pregnant NMRI mice using the avidin-biotin complex immunocytochemical procedure and an antiserum against highly purified porcine relaxin. The immunostaining was measured by immunodensitometry. Relaxin immunostaining was first observed in luteal cells of type I gestational CL on day 11.5 (D11.5). For each investigated day, all CL were identically stained, and immunostaining was evenly dispersed all over the CL. Seventy-five percent of cells were stained at D11.5, and nearly all cells were stained between D13.5 and D18.5. The staining intensity increased throughout the last half of pregnancy, reaching a maximum at D18. A few hours before parturition, at D18.5, relaxin immunostaining decreased dramatically and reached the background level shortly after delivery. From our results we may conclude that, in murine CL, the number of relaxin-secreting cells and the intracellular storage of the peptide increase during pregnancy. The disappearance of relaxin with the cells occurs rapidly +/- 12 h before parturition. PMID- 2265797 TI - Ultrasonographic measurement of fetal lung. AB - Fetal lung measurements were obtained by ultrasonographic examination on 103 normal pregnancies between 18 and 41 weeks' gestation. A linear relationship between right, left and total lung circumference and gestational age was observed. The chest and heart circumference correlated well with gestational age (p less than 0.001). The ratio of left lung circumference to right lung circumference remained virtually constant throughout gestation. However, the ratios of total lung circumference to chest circumference and heart circumference to chest circumference increased significantly (p less than 0.001) with gestational age. PMID- 2265799 TI - Age distribution of erythrocyte population in late pregnancy. AB - The age population distribution of erythrocytes in late pregnancy was evaluated by the volume and density distribution of cells. This approach enables an evaluation of the life span of erythrocytes in the circulation without using radioactive elements. A younger cell population was found in the circulation of women in late pregnancy as compared to nonpregnant women of similar ages, which might be indicative of shortened life span of erythrocytes. This shortened life span might be explained by the fact that erythrocytes made under conditions of increased erythropoiesis and/or increased metabolic rate show acceleration of senescence. This indication of reduced life span of the erythrocytes in late pregnancy may contribute to the understanding of the increased erythropoiesis on the one hand, and reduced hemoglobin concentration on the other hand, which often occurs in late pregnancy. PMID- 2265798 TI - Amniotic fluid catecholamine metabolites in maternal smoking. AB - The concentration of dopamine (DA), norepinephrine (NE), and its metabolites 3 methoxy-4-hydroxy-phenylethylene glycol (MHPG) and vanillyl mandelic acid (VMA), and prostaglandins E2, and F2a in amniotic fluid were measured at labor (1-3 cm of cervical dilatation), in uncomplicated and complicated pregnancies. The amniotic fluid concentration (mean +/- SD) of MHPG in maternal smoking (S) (30.6 +/- 11.9 nmol.mg creatinine-1) and intrauterine growth retardation (IUGR) (36.7 +/- 15.2 nmol.mg creatinine-1) groups is significantly higher than in uncomplicated pregnancies (C) (22.9 +/- 8.8 nmol.mg creatinine-1), or diabetes mellitus groups (D) (26.1 +/- 10.9 nmol.mg creatinine-1) groups; VMA presents similar differences between groups S (145.8 +/- 84.4 nmol.mg creatinine-1) and IUGR (173.0 +/- 135.4 nmol.mg creatinine-1) higher than C (58.3 +/- 26.1 nmol.mg creatinine-1) and D (76.8 +/- 49.0 nmol.mg creatinine-1) groups. NE levels differ between groups in a similar way, but DA does not present significant differences between groups. Prostaglandin levels are higher in the S than in the C group. Nicotine action and/or hypoxia are proposed as a possible cause of NE, MHPG, and VMA rise in amniotic fluid of S, and IUGR versus C or D groups. PMID- 2265800 TI - Serum-specific antibodies for Chlamydia trachomatis in preterm premature rupture of the membranes. AB - A case control study was performed to examine possible morbidity associated with Chlamydia trachomatis in 15 pregnant women with idiopathic preterm premature rupture of the membranes (PROM; group A), and in two control groups, 35 healthy preterm pregnant women (group B), and 43 healthy pregnant women at term (group C). Serum C. trachomatis IgG and IgA specific antibodies were determined using the single serovar (L2) inclusion immunoperoxidase assay. There were no significant differences in the prevalence rate of elevated levels of chlamydia IgG specific antibodies (titer greater than or equal to 1:128) between pregnant women suffering from idiopathic preterm PROM, as compared to healthy preterm and term pregnant women (20, 28 and 26%, respectively). Nor were there any significant differences in the prevalence rate of elevated levels of chlamydia IgA specific antibodies (titer greater than or equal to 1:16) between pregnant women with idiopathic preterm PROM, as compared to healthy preterm and term pregnant women (20, 20 and 17%, respectively). These findings do not support the assumption that C. trachomatis may play role in preterm PROM. PMID- 2265801 TI - Inguinal pelviscopy. A new approach for examining the pelvic organs. AB - Inguinal pelviscopy is a new approach for examining structures in the extra- and intraperitoneal pelvic cavity. The total number of patients studied was 70. The method was used to visualize and take biopsies from masses in the presacral area (3 patients) and in the ovaries (8 patients). Ovarian biopsies were taken from 26 patients (14 with primary amenorrhea and 12 with elevated follicle-stimulating hormone), and ovarian cyst aspiration and biopsy were performed in 12 patients. Tubal sterilization was done in 18 cases and lysis of pelvic adhesions in 3 infertile patients. The procedure comprises entry of the extraperitoneal pelvic cavity through the inguinal canal. Intraperitoneal pelvic cavity examination can also be done by piercing the peritoneum at the deep inguinal ring or close to the fallopian tube. No complications were encountered except urinary retention in 1 patient with presacral tumor and abdominal wall hematoma in another patient. The approach is safe, direct and easy. It is performed on an outpatient basis. PMID- 2265802 TI - Human in vitro fertilization using spermatozoa capacitated in hyperosmotic media. AB - In two separate prospective randomized series of 38 and 16 attempts of human in vitro fertilization (IVF), respectively, the fertilizing abilities of human spermatozoa capacitated in hyperosmotic media and in normosmotic medium were compared. Oocytes from each IVF attempt were divided into two equal groups and inseminated with spermatozoa incubated for 2 h in medium with an osmolality of 285 mosm/kg or in hyperosmotic medium of 315 (first experiment) or 345 mosm/kg (second experiment). The fertilizing capacity of the spermatozoa was not affected by incubation in medium of 315 mosm/kg as compared to spermatozoa incubated in medium of 285 mosm/kg. However, the fertilizing capacity of the spermatozoa incubated in medium of 345 mosm/kg was significantly reduced. The present study indicates that there is no advantage in the use of hyperosmotic media of 315 or 345 mosm/kg for capacitation of spermatozoa in human IVF. PMID- 2265803 TI - Sensitivity of the human myometrial adenylate cyclase to calcium and calmodulin. AB - The calcium-calmodulin-dependent regulation of adenylate cyclase was studied in membranes from pregnant human myometrium. In the absence or presence of exogenous calmodulin, free calcium concentrations greater than 50 nmol/l inhibited the adenylate cyclase activity. Activation of the enzyme by calmodulin (0.1-1 mumol/l) was calcium-dependent and maximal at 10 nmol/l free calcium. The myometrial adenylate cyclase activity was stimulated by the guanyl nucleotide, Gpp(NH)p. In the presence of the guanyl nucleotide, the activatory effect of the calcium-calmodulin complex disappeared. The activatory effect of exogenous calmodulin was dependent on endogenous calmodulin present in the myometrial membranes. Trifluoroperazine and calmidazolium were able to inhibit the adenylate cyclase activity. PMID- 2265804 TI - Different antibody response against Candida albicans cell wall antigens in cervicovaginal secretions of patients with vulvovaginal candidiasis. AB - Vaginal washings from 118 women were investigated by means of immunofluorescence for the presence of antibodies against Candida albicans. A significantly (p less than 0.02) higher antibody titer was found in the samples from patients with clinically evident vulvovaginal candidiasis. Vaginal secretions from those patients with a positive culture for C. albicans were assayed by means of Western blotting. A distinct band pattern was found in the group of patients with a positive culture and the classical clinical picture of C. albicans vulvovaginitis. PMID- 2265805 TI - CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers. AB - Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers. PMID- 2265806 TI - Rubella-specific IgM in reinfection and risk to the fetus. AB - A case of reinfection with the wild rubella virus in the 8th gestational week is reported. The patient had preexisting hemagglutination inhibition antibodies of low titer following immunization with rubella vaccine. Reinfection was accompanied by clinical symptoms and the presence of rubella-specific immunoglobulin M (IgM) of high titer. Following termination of pregnancy no rubella virus could be isolated from the fetal tissues and the fetal blood contained no specific IgM antibodies. These results should encourage the use of cordocentesis before decision on interruption of pregnancy. PMID- 2265807 TI - Association of microscopic gonadoblastoma and contralateral ovarian fibroadenoma in patients with gonadal dysgenesis and Turner phenotype. AB - A rare case of microscopic gonadoblastoma associated with gonadal fibroadenoma in a patient with gonadal dysgenesis and Turner phenotype is reported. The higher incidence of tumor pathologies in patients with gonadal dysgenesis presenting a Y chromosome in their karyotype is discussed, and the need for judicious microscopic analysis of the gonadal streaks of these patients for the detection of possible incipient tumors is emphasized. PMID- 2265808 TI - Footprint analysis between three and seventeen years of age. AB - Footprints of both feet were analyzed from 1676 schoolchildren of both sexes (1013 girls and 663 boys), aged between 3 and 17 years. The sample was divided into five age groups. In each footprint the Footprint Angle and the Chippaux Smirak Index were obtained. Classification of individual shapes of foot arches and different types of foot morphology followed that used by Jaworski and Puch in 1987. A high percentage of lowered longitudinal medial arch in the youngest age group of the study was found. The percentage is lower in the older age groups. The longitudinal medial arch has a physiological development in the earlier years of growth. PMID- 2265809 TI - Screw hole preparation in foot surgery. PMID- 2265810 TI - Correction of hallux valgus with metatarsocuneiform stabilization. AB - 51 feet in 30 patients were evaluated clinically and radiographically an average of 27.6 months after undergoing a modified McBride bunionectomy with a metatarsocuneiform stabilization. An inlay block of bone was used after achieving corrected position of the first metatarsal. The retrospective review included an anteroposterior x-ray, in which definite trabecular bridging was present in only 25.5% of the cases. The metatarsocuneiform joint was asymptomatic regardless of its x-ray appearance. The average intermetatarsal angle was reduced from 14.6 degrees to 8.7 degrees. This procedure attempts to restore near-normal anatomy, thereby preventing transfer metatarsalgia from shortening or elevation of the first metatarsal. Acceptable correction is possible in both moderate and severe deformities. PMID- 2265811 TI - A biomechanical in vitro comparison of open versus percutaneous repair of tendon Achilles. AB - A study was undertaken to compare the in vitro strengths of percutaneous Achilles tendon repair to open Achilles tendon repair. Ten fresh frozen cadaver below-the knee specimens underwent Achilles tenotomy. The specimens were divided into two groups of five specimens each. Group I specimens underwent open Achilles repair using a Bunnell suture technique. Group II specimens underwent percutaneous repair. Each specimen was placed on an apparatus which produced progressive ankle dorsiflexion. Measurements of anastomotic gap were correlated with angle of dorsiflexion. Group I anastomoses were able to resist almost twice the amount of ankle dorsiflexion compared to Group II anastomoses (P less than .05). Entrapment of the sural nerve occurred in three out of five specimens in Group II. Percutaneous anastomoses were malaligned in four out of five specimens. Based on this study, percutaneous repair of Achilles tendon ruptures provides approximately 50% of the initial strength afforded by open repair. Percutaneous repair places the sural nerve at risk for injury. PMID- 2265812 TI - Deep peroneal nerve entrapment on the dorsum of the foot. AB - The anatomic site of entrapment of the deep peroneal nerve's sensory branch over the dorsum of the foot is described. The clinical syndrome in 20 patients is reported. An operative approach to release the entrapment is illustrated. The results in twenty nerves in eighteen patients followed a mean of 25.9 months after surgery is excellent in 60%, good in 20%, and not improved in 20%. PMID- 2265813 TI - Congenital variations of the peroneus quartus muscle: an anatomic study. AB - There has been little research concerning this muscle since the 1920s, when Hecker described this muscle to be present in (13%) of his dissections of cadaver legs. The purpose of our dissections was to establish the incidence of the peroneus quartus muscle, its origins, and insertions. One hundred and twenty-four legs from 65 fresh human cadavers were dissected under loupe magnification. When the peroneus quartus tendon was found, its origin, insertion, and anatomic relationship to the peroneus longus and peroneus brevis were observed. All specimens were sketched and photographed. The peroneus quartus muscle was present in 27 legs (21.7% of specimens). Its origins, insertions, and size varied. In 17 legs (63%) the muscle originated from the muscular portion of the peroneus brevis, and inserted on the peroneal tubercle of the calcaneus. The peroneal tubercle was hypertrophied at the insertion in most cases. The results of this study in general show that there was much higher incidence of the peroneus quartus muscle than Hecker claimed. Its course, origin, and insertion varied. Its tendon can be used for reconstructive procedures about the lateral aspect of the ankle, especially in anterior dislocation of the peroneal tendons and reconstruction of lateral ligaments. PMID- 2265815 TI - A function of the talocalcaneal joint during running support. AB - This study explored the possible function of the talocalcaneal joint during running support to minimize frontal plane rotation of the leg and thereby protect the knee from excessive frontal plane motions. The lower limb was modeled as two rigid segments representing the foot and the leg. The results indicated that for extreme ground-foot angles the talocalaneal joint was able to maintain the knee in a stable position in the frontal plane. It was concluded that the joint may function to minimize frontal plane rotation of the leg and thereby protect the knee from excessive frontal plane motions. The relevance of this function for a below-the-knee-amputee patient lies in the potential for improved prosthetic design. PMID- 2265814 TI - Tarsometatarsal involvement in juvenile spondyloarthropathy. AB - Patients with juvenile spondyloarthropathy who carry HLA B27 antigen or have a family history of ankylosing spondylitis may have marked tarsometatarsal arthritis. This may be associated with hindfoot involvement and result in a supination deformity. Spontaneous fusion with complete obliteration of the tarsometatarsal joints may occur. PMID- 2265816 TI - The ballet technique shoe: a preliminary study of eleven differently modified ballet technique shoes using force and pressure plates. AB - Ballet dancers are vulnerable to various stress-related injuries; foot and ankle injuries are the most common. This study determined if the pressure across the foot could be more evenly distributed by wearing various modified technique shoes padded with PPT, Spenco, or Sorbathane, alone or in combinations. A professional ballet dancer performed a jump by taking a single step on his left foot, jumping and landing with his right foot on the force and pressure plates with each modified shoe plus one unmodified shoe. The results of this study revealed: (1) total force cannot be reduced, (2) center of gravity and the majority of the pressure is maintained over the first and second metatarsal heads, and (3) the modified technique shoe can more evenly distribute pressure to the medial arch and away from the toes, metatarsal heads, and heel. PMID- 2265817 TI - [Where does the road of osteoporosis lead? International meeting of experts "Therapeutic concepts of osteoporosis in the light of new discoveries." Vienna, April 7, 1990. Proceedings]. PMID- 2265819 TI - [Characteristics and clinical significance of silent myocardial ischemia during ambulatory electrocardiographic monitoring in patients with ischemic heart disease]. AB - The purpose of this study was to clarify the clinical and prognostic significance of silent myocardial ischemia (SMI) in patients with proven ischemic heart disease using ambulatory electrocardiographic monitoring (AEM). A total of two hundreds and ninety one patients, including 131 patients with stable effort angina (EA), 125 with previous myocardial infarction (MI), 21 with variant angina (VA), and 14 with unstable angina (UA) were examined. In 141 (EA 65, MI 41, VA 21, UA 14) of these 291 patients, we investigated the frequency and characteristics of SMI. During daily activities, 47% (125/268), 73% (99/136), 71% (140/196), and 69% (102/147) of all transient ST-segment deviations observed was asymptomatic in patients with EA, MI, VA, and UA, respectively. When patients exhibiting only symptomatic episodes were compared with those exhibiting only asymptomatic ones, asymptomatic episodes tended to be associated with the greater duration and magnitude of ST-segment deviation. On the other hand, in patients exhibiting both symptomatic and asymptomatic episodes, the duration and magnitude of ST-segment deviation were greater for symptomatic than asymptomatic episodes. In addition, we also investigated the relation between the result of AEM after standard medical therapy and long-term prognosis in 208 (EA 99, MI 109) of 291 patients. In MI, during the mean follow-up period of 41.2 months, cumulative cardiac event rate was significantly higher in patients with only asymptomatic episodes (SMI group) as well as patients with symptomatic episodes (angina pectoris, AP group) than in patients without any ischemic episodes (Control group). There was no statistically significant difference in prognosis between AP group and SMI group in MI, or among the three groups in EA. These results lead us to conclude that: (1) SMI is observed frequently in patients with ischemic heart disease during daily activities. (2) Asymptomatic episodes are not necessarily less severe in myocadial ischemia than symptomatic episodes. (3) The presence of SMI, as well as angina pectoris, may identify a high-risk group for the development of subsequent unfavorable outcomes while on standard medical therapy. PMID- 2265818 TI - [Conformational changes of rat liver fatty acid binding protein induced by long chain fatty acid]. AB - Rat Liver fatty acid binding protein (FABP) has been purified to homogeneity by the procedures including Sephadex G-100 and DEAE-cellulose column chromatography. FABP was resolved into two peaks of A and B by DEAE-cellulose column chromatography. Each of these fractions exhibited apparent homogeneity upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate with a molecular weight of 16,000 daltons and amino acid analysis of these fractions has revealed that they are identical protein. However, upon isoelectric focusing on polyacrylamide gel, the isoelectric (pl) points were differed considerably showing microheterogeneity. In the present investigation, one isoform (pl = 5.0) of FABP was purified by a successive DEAE-cellulose column chromatography and used for the subsequent experiments of fatty acyl-protein interactions. When the final FABP preparation was partly freed of fatty acids by a mild delipidation technique using Lipidex, the pl shifted toward higher regions of 7.0. However, the pl of the delipidated FABP turned to the original 7.0 by recombining fatty acids. On the other hand, the secondary and tertiary structures were also significantly changed by delipidization, which have been demonstrated by circular dichroism (CD) and nuclear magnetic resonance (1H-NMR) spectroscopy. Furthermore the structural properties of the delipidated FABP also could be restored by recombining fatty acid. These findings suggested that the weakly bound fatty acids are responsible for the functional capacity of the FABP by virtue of changing the protein conformation. PMID- 2265820 TI - [Genetic control of experimental autoimmune uveitis in rats]. AB - Differences in susceptibility to experimental autoimmune uveitis (EAU) among rats of various strains have been reported. The present study was aimed at separating the effects of the major histocompatibility antigen complex (MHC) and non-MHC genes on the development of EAU. EAU-susceptible LEW, EAU-resistant WKAH, WKAH, 1L MHC congenic strain rats representing MHC of LEW on WKAH genetic background, and other nine inbred strains of rats were examined for their ability to develop EAU by immunization with bovine S-Ag or peptide M, an synthetic polypeptide corresponding to position 303 to 320 in bovine S-Ag. We found that only LEW rats developed S-Ag induced-EAU, where WKAH, 1L congenic and other rats did not. However, when an additional injection of Bordetella pertussis (BP) was given, all rat strains developed S-Ag induced-EAU. In contrast, only LEW, WKAH, 1L,F344, and NIG-III rats, which have haplotype 1 at RT1 class II subregions developed EAU by immunization with peptide M and BP. The present findings showed that the susceptibility to EAU in rats was controlled by both MHC and non-MHC genes. Eventual development of EAU in rats was governed by non-MHC gene (s). However, this effect of non-MHC gene (s) could no longer be observed when an additional injection of BP was administered. MHC class II (RT1(1] restricted the susceptibility to peptide M induced-EAU. However, this MHC restriction was not observed when multideterminant S-Ag was used as an immunogen. PMID- 2265821 TI - Micro-architectures of the osseous spiral laminae and spiral limbus in the mouse cochlea: a scanning electron microscopic study on the morphological basis of the auditory mechanics. AB - The auditory mechanics in the cochlea are closely related to the structural variations along the cochlear duct. In this study, the auditory teeth of the spiral limbus and the primary and secondary osseous spiral laminae in the mouse were examined along the entire course of the cochlear spiral by scanning electron microscopy (SEM) after removing the cochlear duct epithelium or the organic material with chemical maceration methods. The cochlear canal consisted of a hook and a spiral of one and half turns and the three-dimensional images and surface structures of the connective tissue forming the spiral limbus including the auditory teeth and the osseous spiral laminae are well demonstrated; the widths of the primary and secondary laminae, the spiral fissure between the two laminae, the tympanic lip, and the vestibular lip with the auditory teeth were measured, and the population density of the auditory teeth were determined in the hook and every half turn. The findings suggest that, in the cochlea the width of the basilar membrane increases in the hook and is almost constant in the spiral portion, the amount of fibers in the basilar membrane linearly decreases from the base to the apex, the displacement mode of the pillar cells during basilar membrane vibrations differs between the apical region lacking the bony edge of the tympanic lip and the other regions with bony edge, the connective tissue fibers from the auditory teeth are inserted to the bone surface of the primary lamina to support the teeth, the teeth on the marginal side of the vestibular lip maintain the stability of the tectorial membrane which is vibrating together with the basilar membrane in response to high frequency sounds on the basal side of the cochlear duct and low frequencies on the apical side, and the interdental cells on the Reissner membrane side maintain the size of the tectorial membrane which shows a linear increase in size from the base to the apex of the cochlear duct. PMID- 2265822 TI - [A case of early gastric cancer disappeared by endoscopic polypectomy and local injection of anti-cancer agent associated with systemic immunochemotherapy]. AB - A 78-year-old female was diagnosed as having an early gastric cancer of II a (+II c) type with probable sm invasion by gastroscopic examination. Endoscopic polypectomy was carried out due to advanced age, severe ischemic heart disease, and refusal of surgical treatment. Most of the cancerous tissue were removed endoscopically, but biopsy specimens after polypectomy showed some tumor cells leaving at the excisional site. She was treated with local injection of OK-432 endoscopically, PSK orally, Tegafur rectally, and Lentinan intravenously. After about 7 months' treatments, biopsy specimens revealed no residual cancer cells. The total doses administered up to cure for cancer were 70 KE of OK-432, 141 g of PSK, 99 g of Tegafur, and 45 mg of Lentinan. The combination therapy with massive removal of cancer tissue by endoscopy, local injection of anti-cancer agent to residual cancerous lesion and systemic immunochemotherapy will be available and recommendable for poor risk patients with early gastric cancer. PMID- 2265823 TI - Nuclear architecture of human pachytene spermatocytes: quantitative analysis of associations between nucleolar and XY bivalents. AB - Nucleolar association and heterochromatin coalescence have both been invoked as mechanisms involved in the origin of chromosomal associations between nucleolar bivalents themselves, as well as between these bivalents and the XY pair, during meiotic prophase in human spermatocytes. However, these mechanisms do not satisfactorily explain how associating bivalents meet each other within the nuclear space. To elucidate this problem, we have characterized different types of nucleolar-nucleolar and nucleolar-XY bivalent associations, and their frequencies, in light and electron microscope serial sections of spermatocyte nuclei. In the pachytene nucleus, nucleolar bivalent associations were found to involve only one nucleolar sphere of RNP granules connected through a fibrillar center to a chromatin mass composed of two, or more, nucleolar-bivalent short arms. Structural relationships between these elements were examined using 3D computer models of various nucleolar associations. XY and nucleolar bivalents were usually located towards the nuclear periphery associated with the inner face of the nuclear envelope. Some nucleolar bivalents, whether single or associated appeared beside or over XY chromatin. When nucleolar-bivalent short arms (BK) were found over nucleolar or over XY chromatin, their telomeres were unattached to the nuclear envelope and the corresponding synaptonemal complexes were not observed. Ninety nucleoli were found in sixty pachytene nuclei. Thirty six percent of these nucleoli were bound to associated BKs and the remaining 64% to single BKs. Over 40% of individual spermatocytes showed at least one cluster of associated BKs and about 20% presented single or multiple BKs associated with the XY pair. The frequencies of random BK associations, over the total or restricted areas of the nuclear envelope, were calculated according to a probabilistic nuclear model. A correspondence was found in comparing the observed frequencies of associated BKs with those calculated on the basis of bouquet formation. Such an analysis strongly suggests that the occurrence of associations between nucleolar bivalents may arise at random within the bouquet. Thus, the architecture of the meiocyte nucleus, particularly the organization of the bouquet, may be the primary mechanism by which nucleolar bivalents meet each other and, consequently, become associated either through common nucleolus formation or by heterochromatin coalescence. PMID- 2265824 TI - The 60 and 63 kDa proteolytic peptides of the red cell membrane band-3 protein: their prevalence in human and non-human primates. AB - Three phenotypes based on the polymorphism of band-3 protein from human red cells are described. Limited proteolysis of intact red cells from most individuals (homozygotes) yields a peptide of 60 kDa, but in some cases (heterozygotes), there is also a 63-kDa peptide, and rarely only the single peptide of 63 kDa is found. This is the first description of the 63-kDa homozygote. The interpretation that the three phenotypes are controlled by two alleles of a single autosomal locus, with no dominance, is supported by population and family studies. The frequencies of the allele, which we designate as p63, is 0.041 +/- 0.0068 in Caucasoids and 0.125 +/- 0.0121 in Negroids. The electrophoretic profiles and molecular weights of the peptides obtained with several commercial proteases from Streptomyces griseus are similar to those obtained with chymotrypsin. Whereas band-3 protein in two New-World monkeys (Saimiri and Cebus) resisted pronase attack, an Old-World monkey (Macaca mulatta) was monomorphic for a 63-kDa fragment, and in an ape (Pan troglodytes), a doublet of 62 kDa and 64 kDa was found. Band-3 protein polymorphism appears to be a good marker for genetic differentiation in human populations. PMID- 2265825 TI - In search of a genetic basis for the Rett syndrome. AB - Rett syndrome is a progressive encephalopathy restricted to the female sex. In the present paper a possible genetic cause for this syndrome is discussed, based on data from the literature as well as our own. Our results are in agreement with others regarding no increase in parental age, or in spontaneous abortions rate among the mothers of affected children and with a normal sex ratio among sibs. We have found no chromosome rearrangement detectable with the methods used and no correlation between fra(X) (p22) and the Rett syndrome. We have observed an alteration in the sequence of replication in one of the two types of late replicating X-chromosome present in normal women, and suggest that this may signify that genes which are active in the late-replicating X-chromosome are inactivated (or vice-versa) in these patients. This fact could be related to the abnormal phenotype observed in Rett syndrome patients. PMID- 2265826 TI - Cytogenetic and molecular analysis of a Yq isochromosome. AB - The dicentric Yq isochromosome of a male with azoospermia and some features of Klinefelter's syndrome was examined using cytogenetic and molecular methods. C- and R-banding of chromosomes of peripheral blood lymphocytes revealed a complex mosaic consisting of 46,X,i(Yq)/45,XO/46,XY/47,XYY/47,XY, i(Yq)/47,X,i(Yq),i(Yq) cells. EBV-transformed lymphocytes either had a 46,X,i(Yq) (90%) or a 46,X, + mar (10%) karyotype. The marker chromosome was shown to be Y-derived by in situ hybridization. C-banding, quinacrine- and DA/DAPI-staining indicated inactivation of one of the centromeres in almost all Yq isochromosomes. The use of Y chromosomal DNA sequences demonstrated that most of the Y chromosome, including its short arm, was duplicated. PMID- 2265827 TI - Partial complementation of the Fanconi anemia defect upon transfection by heterologous DNA. Phenotypic dissociation of chromosomal and cellular hypersensitivity to DNA cross-linking agents. AB - Transfectants obtained by mouse DNA-mediated gene transfer in Fanconi anemia (FA) primary fibroblasts from the genetic complementation groups A and B were examined for the frequencies of chromosomal aberrations and cytotoxicity following treatments by cross-linking agents. Cells from group A (FA 150), which is the most sensitive to such agents, are partially corrected for both the chromosomal and cellular hypersensitivity to 8-methoxypsoralen photoaddition. In contrast, after treatment with mitomycin C (MMC), only the chromosomal sensitivity is re established to a near normal level. The opposite is true for FA group B cells (FA 145), i.e. cell survival to MMC is partially corrected, whereas the frequency of MMC-induced chromosomal aberration remains close to that of the untransfected cells. The partial phenotypic correction of the two end points examined is interpreted as indicating either a gene dosage effect or the necessity of introducing more than one gene type in order to achieve complete recovery of a normal phenotype. The phenotypic dissociation between the clastogenic and cellular hypersensitivity to cross-linking agents may offer the opportunity of isolating separately the responsible gene(s) by conventional rescue techniques. PMID- 2265828 TI - Infertility in human males with autosomal translocations: meiotic study of a 14;22 Robertsonian translocation. AB - Pachytene analysis was undertaken in a male patient heterozygous for a 14q22q Robertsonian translocation. The relatively low rate of XY autosome association led us to examine the relationships existing between the chromosomes involved in the translocation, the rate of XY-autosome association and the degree of spermatogenic failure. Cytogenetic investigations in infertile men and the results of the meiotic studies suggest a direct correlation between the frequency of XY-autosome association at pachytene and the degree of spermatogenic failure. Whether associations arise as a consequence or cause of germ cell failure is still not certain. PMID- 2265829 TI - Assignment of human tracheobronchial mucin gene(s) to 11p15 and a tracheobronchial mucin-related sequence to chromosome 13. AB - Extensive heterogeneity of tracheobronchial mucin RNAs has been described recently. Based on the results of total or partial cDNA sequencing, the mucin cDNAs obtained were classified into three groups. The first group contained 24 bp tandem repeat sequences, the second exhibited homology at their amino- and carboxyl-terminals, and the third group seems to consist of alternative hydrophilic-hydrophobic zones. JER58, JER47 and JER57 probes, representing the first, second, and third tracheobronchial mucin families respectively, were used for chromosome assignment. In human DNAs digested with BamHI, the JER58 probe detected a sequence of 21 kb, the JER47 probe detected a major sequence of 21 kb and a minor sequence of 4 kb, and the JER57 probe detected two sequences of 1.8 kb and 1.3 kb. By somatic hybrid cell analysis, the JER58. JER47, and JER57 major sequences were assigned to chromosome 11 and the JER47 minor sequence to chromosome 13. By in situ hybridization the JER58, JER47 and JER57 probes were assigned to 11p15. Under the experimental conditions used, no specific hybridization to the chromosome 13 region was observed with the JER47 probe. Our results indicate that tracheobronchial mucin gene(s) is/are localized on 11p15. The minor JER47 BamHI sequence localized on chromosome 13 probably corresponds to a tracheal-mucin related sequence. The intestinal mucin gene was also recently localized to the same 11p15 region. Intestinal and tracheobronchial mucins appear different according to their tissue distribution and their cDNA nucleotide sequences. Tracheal mucin probes (JER58, JER47, JER57) and intestinal probes may represent independent genes on 11p15 or else different mRNAs from the same primary transcript produced by differential splicing. Further studies using mucin genomic probes for 11p15 will be required for the elucidation of tracheal and intestinal mucin gene organisation in this region. PMID- 2265830 TI - Translocation t(1;17)(q12;q25) with a clinical picture like of a proximal deletion of 1q: identification by in situ hybridization with chromosome 1 specific satellite DNA probes. AB - The authors report a case of a balanced 1;17 translocation with breakpoints located in the secondary constriction of chromosome 1. This translocation is associated with pathological symptoms similar to those observed following a proximal deletion of 1q. We request contact with colleques who have observed similar, or related, cases of translocation with breakpoints in heterochromatic regions of human chromosomes. PMID- 2265832 TI - Changing paternal age distribution and the human mutation rate in Europe. AB - All available evidence indicates that the human mutation rate increases with paternal age. In developed countries, a reduction in the proportion of older parents is a common feature of the marked changes in parental age distribution that occur as a result of family planning. We have related the current paternal age distribution in the European countries for which data is readily available, to a derived curve for paternal age-specific relative mutation rate. The results indicate that, to the extent that it is dependent on paternal age, the mutation rate has decreased considerably in developed countries during the past 50 years. The human mutation rate is a dynamic entity, continuously changing in response to social conditions. PMID- 2265831 TI - Assignment of the gene for central core disease to chromosome 19. AB - In a large kindred in which the gene for central core disease is segregating, we have demonstrated linkage between the disorder and a marker on chromosome 19q. Marker D19S9 (p1J2) was linked to central core disease with a lod score of 6.4 at theta = 0.03 (support interval 0.01-0.14) thus localizing the gene for this disorder in or very close to 19q12-q13.2. PMID- 2265833 TI - Hereditary retinoblastoma: can balanced insertion entirely explain the differences of expressivity among families? AB - Although the retinoblastoma gene has been isolated and sequenced, the difference in penetrance and expressivity among families has not yet been fully explained. Balanced chromosomal insertion involving the 13q14 regions has been shown to account for some families with several unaffected carriers. Since there could be cases with karyotypically undetectable insertions, we tested whether this mechanism was general enough to explain the whole difference in expressivity among families. Using 166 pedigrees, reported in nine series available in the literature (including our own), we conclude that balanced insertion cannot entirely explain the familial data, even if we allow for a reduced viability of unbalanced gametes. Other mechanisms are proposed and discussed in this paper. PMID- 2265834 TI - Heterozygous expression of X-linked chondrodysplasia punctata. Complex chromosome aberration including deletion of MIC2 and STS. AB - Two females showing partial expression of X-linked chondrodysplasia punctata were identified in a family. Bone dysplasia was caused by an aberrant X chromosome that had an inverse duplication of the segment Xp21.2-Xp22.2 and a deletion of Xp22.3-Xpter. To characterise the aberrant X chromosome, dosage blots were performed on genomic DNA from a carrier using a number of X-linked probes. Anonymous sequences from Xp21.2-Xp22.2 to which probes D2, 99.61, C7, pERT87-15, and 754 bind were duplicated on the aberrant X chromosome. The proposita was heterozygous for all these markers. Dosage blots also showed that the loci for steroid sulfatase and the cell surface antigen 12E7 (MIC2) were deleted as expected from the cytogenetic results. Mouse human cell hybrids were constructed that retained the normal X in the active state. Analysis of these hybrid clones for the markers from Xp21.2-Xp22.2 revealed that all the alleles of the informative markers, present in a single dosage in the genomic DNA, were carried on the normal X chromosome of the proposita. The duplicated X chromosome therefore had two identical alleles, indicating that the aberration resulted from an intrachromosomal rearrangement. PMID- 2265835 TI - A recombination map of the human X-chromosome. AB - A family with 11 normal boys has been typed with DNA probes spanning the whole of the X-chromosome to observe directly the recombination events in 11 meioses from one female. This has (a) identified apparent recombination hot-spots on the X chromosome; (b) shown the positions and numbers of cross-overs that have occurred in the p and q arms; (c) not shown any cross-overs in the centromeric region and (d) enabled the calculation of the genetic length of the X-chromosome. PMID- 2265837 TI - The major cystic fibrosis mutation in a British population. AB - We have studied 72 families with at least one child with cystic fibrosis (CF); they were referred because they had requested prenatal diagnosis in a future pregnancy. The delta F508 mutation was found in 108/140 CF chromosomes (77%). In 41/72 families (57%), both parents carried a deleted chromosome and the child was doubly deleted. In only 4 families, 2 of them being consanguineous, did neither parent carry a deleted chromosome. Meconium ileus was associated with children who were delta F508/delta F508, delta F508/non-deleted and non-deleted/non deleted. PMID- 2265836 TI - Abnormal hemoglobins in the Silk Road region of China. AB - A review is presented of the occurrence of 24 abnormal hemoglobins (13 alpha chain variants and 11 beta-chain variants) in populations in the Silk Road area of Northwestern China. Most frequently occurring were Hb D-Punjab [beta 121(GH4)Glu----Gln] in Uygurs, Kazaks, and Khalkhas, Hb G-Taipei [beta 22(B4)Glu- --Gly] in persons of the Han nationality, and Hb G-Coushatta [beta 22 (B4)Glu--- Ala] in the Uygurs, Kazaks, Hans, and related nationalities. The data suggest that these variants likely originated in Central Asia, in the Han nationality of China, and in the minorities of northern China, respectively. Other variants occurred at considerably lower frequencies and were imported from other countries or arose as independent mutations. Two variants [Hb Tashikuergan or alpha 19(AB1)Ala----Glu; Hb Tianshui or beta 39(C5) Gln----Arg] were observed for the first time. The data from this study of the many variants support the movements of various populations in this area, as reported in numerous historical documents. PMID- 2265838 TI - The gene coding for the alpha-chain of human propionyl-CoA carboxylase maps to chromosome band 13q32. AB - The human gene encoding the alpha-polypeptide of propionyl-CoA carboxylase (PCC) has hitherto been localized to the distal half of the long arm of chromosome 13, segment 13q22----q34. We studied the enzyme activities of mitochondrial carboxylases in cell cultures obtained from patients with different deletions of chromosome 13. By setting the PCC activity in normal diploid cell cultures (control group) at 100%, cell cultures with trisomy 13 showed 150% activity. In contrast, one of four patients with partial monosomy 13 had an enzyme activity of only 50%. Thus, by comparative deletion mapping, combined with studies of the gene-dosage effect, we have been able to assign the PCCA gene locus to chromosome band 13q32. PMID- 2265839 TI - Seroprevalence of HIV-1 infection in a cohort of homosexually active men. AB - A non-clinic cohort of 525 homosexually active men from London and South Wales were recruited in 1988 for a study by interview of sexual behaviour. A sample of blood was tested for HIV-1 antibodies. Seropositivity in London was 9.2% compared with 3.4% in South Wales. Men who were not regular STD clinic attenders had a lower rate of seropositivity than did those who were regular attenders. Men who were seropositive reported more sexual partners with whom they had anal intercourse and also reported more episodes of syphilis. Overall, rates of seropositivity were lower than those reported by studies from STD clinics. PMID- 2265840 TI - Detection of treponemal DNA in the CSF of patients with syphilis and HIV infection using the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in the cerebrospinal fluid (CSF) of patients with and without syphilis. The CSF from 10 of 19 patients with positive serological tests for syphilis who were being investigated for late syphilis were treponemal DNA-positive. In contrast, the CSF from only one of 30 patients with no known history of syphilis was DNA-positive. CSF from 28 HIV-positive patients was also tested. Fourteen of these patients had central nervous system (CNS) disease and seven were DNA-positive, whereas none of the 14 without CNS disease were DNA-positive. Five of the seven DNA-positive patients had a history of syphilis. Such a history in an HIV-positive patient who had CNS disease was predictive of finding treponemal DNA in the CSF. The PCR had a sensitivity of 47% and a specificity of 93% for detecting a known history of syphilis and is a potentially useful tool in treponemal diagnosis. PMID- 2265841 TI - Sexually transmitted diseases in rape victims. AB - From 1 January 1986 to 1 September 1989 124 women presented to the Ambrose King Centre (the department of genitourinary medicine of the London Hospital) alleging rape. Sexually transmitted diseases were found in 36 (29%) women (excluding candidosis and bacterial vaginosis). The commonest organisms detected were Neisseria gonorrhoeae and Trichomonas vaginalis, each being present in 15 patients. Eleven women had genital warts. Chlamydia trachomatis was isolated in six patients, two had herpes simplex virus infection and one patient had pediculosis pubis. Serological evidence of past hepatitis B infection was detected in five women and one patient had antibodies to human immunodeficiency virus. Eighteen of the 36 women (50%) had multiple infections. Six women had abnormal cervical cytology smears, three being suggestive of cervical intraepithelial neoplasia grades II-III. Although it is rarely possible to attribute infection to an assailant, these patients require further counselling, treatment and review. Rape victims are thus a population at risk of having sexually transmitted diseases and screening should be offered. PMID- 2265842 TI - A comparison of four cytological sampling techniques in a genitourinary medicine clinic. AB - Four cytological sampling techniques (the Ayre's spatula alone, the Ayelesbury spatula, the Ayre's spatula in conjunction with a Cytobrush (Medscand), and the Cervex (Steriseal] were compared when used in a genitourinary medicine clinic. Over a period of two years 6991 smears were taken. No difference was found between the methods with regard to detection of dyskaryosis, although there were significant differences in the percentage of smears containing endocervical cells. PMID- 2265843 TI - Is a test of cure necessary following treatment for cervical infection with Chlamydia trachomatis? AB - Tests of cure (TOC) were performed on specimens from 106 women following treatment for chlamydial infection of the cervix. 91 women attended for the first TOC with enzyme immunoassay (EIA) within one week of finishing antibiotics. Three were EIA positive, 88 were EIA negative. These three women were subsequently EIA and culture negative although they received no further antibiotics. Ninety women returned for the second TOC with EIA and culture between seven and 27 days after completing treatment. All the results were negative. Routine TOC is unnecessary following appropriate antichlamydial therapy. If TOC is indicated antigen detection methods should not be used immediately after finishing antibiotics as misleading positive results may be obtained. EIA or culture at one week or later after treatment is reliable. PMID- 2265844 TI - Dot-immunobinding assay with monoclonal antibody for detection of Trichomonas vaginalis in clinical specimens. AB - A rapid and specific dot-enzyme immunoassay (DIBA) using monoclonal antibody was introduced for detection of Trichomonas vaginalis antigen in vaginal and urethral materials. The results of DIBA were compared with culture findings of the parasite in 245 female patients. Taking culture as the reference method, DIBA had a sensitivity of 92% and a specificity of 93%. The predictive value of a positive test was 98% and that of a negative test 77%. The efficacy of wet mount, culture and DIBA were compared in 134 women with trichomonal infection. The most sensitive method was cultivation with a positivity of 99.3%. DIBA was as sensitive as the wet mount (92%). In 51 sexual partners of women with trichomoniasis DIBA proved to be ineffective. The sensitivity of the assay with corpuscular antigen of T vaginalis was 1 x 10(4) cells/ml, with soluble antigen 47 micrograms/ml. Specificity of the assay was confirmed by lack of any cross reactivity with Trichomonas tenax. Tritrichomonas mobilensis and Candida albicans. PMID- 2265845 TI - Avascular necrosis of the hip in a man with HIV infection. AB - The development of an osteonecrotic (avascular necrosis) hip joint in a patient with symptomatic CDC Stage 1V C2 disease is reported. The diagnosis was aided by radiological assessment and confirmed by radioisotope bone scan. This case serves as yet another musculoskeletal manifestation in association with HIV infection. PMID- 2265846 TI - Cymalon in the management of urinary tract symptoms. PMID- 2265847 TI - Longer incubation of an amplified enzyme immunoassay for the detection of Chlamydia trachomatis. PMID- 2265848 TI - Syphilis in art. PMID- 2265849 TI - Focal vulvitis and localised dyspareunia. PMID- 2265850 TI - Serum Gc, Hp and alpha 2HS phenotypes in human T-lymphotropic leukemia virus type I infection. AB - The serum Gc, Hp and alpha 2HS phenotypes were examined in 64 subjects known to have the human T-lymphotropic leukemia virus type I (HTLV-I) infection and in 60 uninfected subjects. There were no significant differences in the distributions of Gc, Hp and alpha 2HS phenotype and allele frequencies between any grouping of HTLV-I-infected subjects and the controls. No association between the Gc, Hp and alpha 2HS genotypes and susceptibility to adult T-cell leukemia was found. PMID- 2265851 TI - Wd(a+) red blood cells in two sisters of a Hei//om Khoisan family in Namibia. AB - Two sisters in a Hei//om family of the southern African Khoisan race in Namibia were found to have Wd(a+) red blood cells. Wda is a low-frequency antigen identified so far only in a European family in Canada and a family in Holland. The Wda gene may have had an independent origin in the Khoisan. Alternatively, the Hei//om population may have acquired it through miscegenation. PMID- 2265852 TI - Orosomucoid (ORM) typing by isoelectric focusing: an analysis of ORM haplotypes. AB - A new separator isoelectric focusing method for typing of orosomucoid (ORM) was developed. This method provided a superior resolution of ORM patterns: two close bands of ORM1*5.2 products were clearly separated. A total of 364 subjects from Okinawa (Japan) were classified into 21 ORM phenotypes determined by 6 ORM1 and 7 ORM2 alleles including a polymorphic silent allele, ORM2*QO, and 2 new rare variants, ORM2*18 and ORM2*19. These phenotypes were also explained by 12 ORM haplotypes, half of which were polymorphic. PMID- 2265853 TI - Association of C3 and C4A complement types with familial amyloidotic polyneuropathy. AB - A mutant variant of the serum protein transthyretin (TTR-met30) appears to be a necessary but not sufficient condition for the development of familial amyloidotic polyneuropathy (FAP). We have studied a number of serum protein markers (alpha 1-antitrypsin, properdin factor B, C3, C4A, C4B, haptoglobin, transferrin and group-specific component) in FAP patients and healthy controls in an attempt to identify additional pathogenic factors which may influence the risk for developing FAP in male and female patients as well as the age of onset of the disease. Statistically significant associations were found in the complement systems C3 and C4A. The C3F variant was significantly increased in all FAP patients with a relative risk (RR) of 2.0, more pronounced in female patients (RR = 2.6) and patients with an early onset of the disease (RR = 4.5). In the FAP patients only the variants A3 and A4 were found in the C4A system. C4A3 was found in all patients, which was significantly higher than in the controls. The remaining serum protein systems showed no statistically significant associations with FAP. The results suggest that genetic variants of complement factors C3 and C4A may interact with the mutant TTR-met30 by modifying the expression and onset of FAP. PMID- 2265854 TI - HLA-associated susceptibility to acquired immune deficiency syndrome in HIV-1 seropositive subjects. AB - No difference in HLA-A, B or DR gene frequencies could be observed between 172 control subjects and 180 HIV-1-seropositive subjects of European ancestry diagnosed through the systematic screening of blood donations. In contrast, progression to acquired immune deficiency syndrome (AIDS; 21 patients) or CD4 lymphocyte loss equal or more than 20% over a 6-month period (37 subjects) was found to be associated with the B8DR3 haplotype (relative risk = 10.64, p less than 0.003, and 2.23, p less than 0.092, respectively). Other independently significant associations assessed through the multivariate Cox proportional hazards model were B16, BW21 and B35 alleles as factors of bad prognosis. Conversely, A11 and DR4 alleles were factors favouring longer survival. PMID- 2265855 TI - Two new orosomucoid (ORM2) variants in Japanese. AB - Orosomucoid (ORM) of plasma from 287 Japanese was typed by polyacrylamide gel isoelectric focusing followed by immunoprinting with specific antiserum to ORM. Two new variants were observed and they were designated ORM2 16 and ORM2 17. PMID- 2265856 TI - Presymptomatic exclusion of myotonic dystrophy in a one-generation pedigree of half-siblings. AB - An unusual one-generation family with myotonic dystrophy is presented, in which genetic counseling was successfully carried out. The probability of an informative result, before marker typing, is analytically derived and amounts to at least 40%. PMID- 2265857 TI - Distribution of human Zn-alpha-2-glycoprotein types in Chinese and Korean populations. AB - The genetic variation in Zn-alpha 2-glycoprotein (ZAG) was investigated by polyacrylamide gel isoelectric focusing and immunoblotting. The samples comprised 590 Chinese from 2 localities (Shenyang: n = 390; Kaohsiung: n = 200) and 873 Koreans from 2 localities (Seoul: n = 523; Cheju: n = 350). The allele frequencies were: ZAG*1 = 0.9962, ZAG*5 = 0.0038 in Shenyang; ZAG*1 = 1.0000 in Kaohsiung; ZAG*1 = 0.9971, ZAG*3 = 0.0029 in Seoul, and ZAG*1 = 0.9929, ZAG*3 = 0.0071 in Cheju. PMID- 2265858 TI - [Does the humoral immune defect syndrome hold a pathogenetic relevance for chronic obstructive bronchitis?]. PMID- 2265859 TI - [Microbiological diagnosis of lower respiratory tract infections]. AB - Successful microbiological diagnosis of lower respiratory tract infections demands a close cooperation between clinician and clinical microbiologist. Because of the broad spectrum of possible respiratory pathogens precise requests are necessary for adequate laboratory procedures. The high rate of potential pathogens requires quantitative microbiological and cytological data in order to differentiate between colonisation and infection. Pathophysiological reactions on microbial colonisation of the bronchial tree may contribute to acute exacerbations of a chronic bronchitis. The precise role of microbial nocuous agents, however, remains to be clarified. PMID- 2265860 TI - [Quantitative determination of immunoglobulin G (IgG) subclasses]. AB - The four IgG subclasses differ with respect to structure and biological function. Within the last 26 years, numerous immunological methods have been developed to study the role of the individual subclasses in humoral immune response. Different methods for quantitative IgG-subclass determinations are discussed with special reference to reliability and standardization. The clinical indications for measuring IgG-subclass levels are listed. PMID- 2265861 TI - [Immunoglobulin G subclass deficiency in patients with asthma and chronic obstructive bronchitis]. AB - In 99 patients with asthma or chronic obstructive bronchitis immunoglobulins and immunoglobulin-G subclasses were measured to characterize the frequency of humoral immune deficiencies. 26 patients had decreased serum levels in one or two IgG subclasses. So IgG-subclass deficiency is a common finding in patients with asthma and obstructive bronchitis. Treatment with corticosteroids seems to promote low IgG-subclass levels, but cannot fully explain alterations of IgG subclasses. Today IgG-subclass deficiencies are regarded as an important factor in the susceptibility to recurrent infections. We think, variation in IgG subclasses may have further effects on the noninfectious inflammatory processes of asthma and obstructive bronchitis. PMID- 2265862 TI - [Therapy with immunoglobulins]. AB - Adequate IgG-replacement therapy as treatment of choice for patients with humoral immunodeficiencies has revolutionized the outcome of these disorders. The action of intravenous immunoglobulins (IVIG) in autoimmune diseases, especially in idiopathic thrombocytic purpura seems to be due to Fc-receptor blockade and immunomodifying qualities. Thus far, treatment for patients with subclass deficiencies is restricted to persons with recurrent infections. PMID- 2265863 TI - [Immediate and late phases of allergic rhinitis]. AB - The allergic reaction of the human nasal mucosa (Type I Coombs and Gell) can be divided in an immediate- and a late-phase reaction. The degranulation of IgE bearing mast cells is crucial for the initiation of the immediate phase (app. 30 min). Mediators of these cells - especially histamine - cause the typical allergic symptoms. Some of the patients develop a late-phase reaction after a symptom-free interval. Eosinophils migrate into the epithelial lining and release mediators. Furthermore, mast cells increase in number in the epithelium. Other cells like macrophages and T lymphocytes may be involved as well. While the released mediators cause an unspecific mucosal hyperreactivity, the increased number of IgE-bearing mast cells leads to a specific immunological augmentation of the nasal reaction ("priming effect"). The allergic pathomechanism can be reduced by drugs at different points. PMID- 2265864 TI - Patterns of cancer in five continents. PMID- 2265865 TI - Changes in drinking behavior: demographic, psychosocial, and biomedical factors. AB - Demographic, psychosocial, and biomedical variables were collected from 12,371 ambulatory persons who had an initial multiphasic health examination in 1978 or 1979 and a second examination 5 years later in 1983 or 1984. Subgroups of this cohort who had substantially increased and decreased their drinking were compared with persons who continued to drink at baseline rates. A balanced model of demographic, psychosocial, and biomedical variables had the capacity to differentiate persons who had substantially increased their drinking; fewer variables--primarily psychosocial--differentiated persons who had greatly decreased their drinking. PMID- 2265866 TI - Compulsory treatment for drug abuse. AB - Using research which shows treatment to be effective in reducing intravenous drug abuse, and the importance of retention in treatment as a determinant of outcome, compulsory treatment is examined and a set of policy and research recommendations are developed. Particularly, civil commitment and court diversion programs are reviewed for their potential impact on reducing the number of intravenous drug abusers at risk for contracting and transmitting the AIDS virus. Recommendations include the provision of: effective methods for detecting drug abusers, appropriate legal protections, systems linkages, treatment, and recognition that drug dependence is chronic. It is also suggested that available treatments such as methadone maintenance be used by the criminal justice system for referrals. PMID- 2265867 TI - Differences between personal and general alcohol-related beliefs. AB - The discrepancy between personal alcohol-related statements and general beliefs regarding alcohol was investigated in a community sample of 283 social drinkers. Discriminant analysis showed that subjects perceived themselves as significantly less dependent than others. "Self" statement responses accurately predicted drinking behavior, as measured by consumption; however, general statements did so less effectively. Medium-heavy drinkers considered others to be dependent on alcohol to change aversive events, suggesting that a self-fulfilling bias may have distorted their perception. For most drinkers the self-other discrepancy seemed best explained by media and societal influences rather than by a self fulfilling bias model. PMID- 2265868 TI - Characteristics of alcoholics and codependents who did and did not complete treatment. AB - Demographic data were collected on 803 patients who were treated for dependency/codependency issues at the Center for Problem Resolution (CPR) from September 1, 1986, until December 31, 1987. Comparisons were made between patients who completed treatment and noncompleters. Results are reported on the entire sample and then broken down into three patient categories. Factors which may be associated with staying in treatment for codependents are previous counseling and health problems. Chemical dependents who tended to finish treatment were female, employed, not detoxing, and willing to commit themselves to an appropriate number of self-help meetings following treatment. PMID- 2265869 TI - Hispanics and illicit drug use: a review of recent findings. AB - This manuscript presents a comprehensive assessment of the current illegal drug use problem among Hispanics by analyzing the recent findings on this subject. Information is provided on the prevalence of illegal drug use by drug type, age, and specific Hispanic group, and on the accessibility and availability of drug treatment facilities to Hispanics. The consequences of illegal drug use upon the well-being of Hispanics are discussed. Recommendations on additional research are made. PMID- 2265870 TI - Australia's media campaign against drug abuse. AB - A quasi-experimental research design found evidence of a weak main effect of the first stage of Australia's media campaign against drug abuse. Although there was no evidence of behavioral or perceptual changes, there was an increase in support for more restrictive antidrinking and antismoking legislation. This effect was enhanced in respondents who were interviewed prior to the campaign. Implications for future media campaigns against drug abuse are considered. PMID- 2265871 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2265872 TI - The debt-depression of the less developed world and public health. PMID- 2265873 TI - Health services and decentralized government: the case of primary health services in Norway. AB - Decentralized forms of government are becoming more common in Western European countries. The effects of decentralization of public health services are explored in this article. In 1984 the Norwegian Municipal Health Act allocated the responsibility for primary health care to the municipalities. Based on data from a sample of 70 municipalities, the author shows that the number of primary health service personnel has expanded considerably during 1984-88, but the distribution of services has not become more equitable. Though the formal role of local politicians in the decision-making process has increased, the health sector officers and the Municipal Executives have in practice controlled the evolution of the municipal health services. The author concludes that decentralization does not necessarily lead to more democracy, and that an equitable distribution of public health services becomes more difficult to attain. PMID- 2265874 TI - The drug swindlers. AB - In a number of important developing nations--among them Indonesia, India, and Brazil--clinical pharmacologists and other drug experts are revealing mounting concern over the marketing of fraudulent drug products. These are shaped, colored, flavored, marked, and packaged to mimic the real product. They may contain the actual antibiotic or other drug indicated on the label, but so "cut" that the product provides only a small fraction of the labeled amount, or they may contain only useless flour or starch. At best, they are worthless. At the worst, they can kill. In most instances, it is believed that these "drugs" are produced and marketed by local or domestic fly-by-night groups and not by multinational pharmaceutical firms. Blame for these practices is placed on inadequate or unenforced laws, only trivial punishments, bribery and corruption, and the fact that generally "nobody inspects the inspectors." PMID- 2265875 TI - Questions and answers on synthetic bovine growth hormones. AB - Questions are posed and answered on synthetic bovine growth (milk) hormones (s BGH), covering a wide range of areas of critical international concern. These areas include: the data base on s-BGH; efficacy and benefits to the dairy industry; veterinary effects; public health effects; Food and Drug Administration approval; and the FDA review process. PMID- 2265876 TI - Section on AIDS: the politics of survival. Introduction. AB - In one short decade, the politics of AIDS has become the politics of survival. In a world whose social order is changing before our eyes, AIDS insistently brings new meaning to the age-old question of what it is we must do to survive--as individuals, as families, as communities, as nations, as members of an interdependent world. The goal of this Special Section is to promote frank discussion, from an explicitly progressive perspective, of what it will take to stop the AIDS epidemic and deal with the devastation it has already wrought. Articles by AIDS researchers, service providers, and activists from around the world will address the numerous social, political, economic, and cultural factors that affect both the spread of AIDS and the social response to the epidemic. Topics to be considered in this and future issues of the Journal include: AIDS and community survival in the United States; women and AIDS, particularly in economically underdeveloped countries; the politics and economics of AIDS interventions in Latin America and the Caribbean; and the growing international AIDS industry. PMID- 2265877 TI - AIDS prevention in the United States: lessons from the first decade. AB - AIDS prevention programs in the United States have been relatively successful in providing accurate information on AIDS to a wide cross-section of the population, but less successful in helping people to change their risk behavior. The most significant changes have been reported in urban gay men, with lower levels of change in drug users, and the least change in young adult heterosexuals. Various obstacles to effective AIDS prevention interventions have been identified, including too great an emphasis on information; a reliance on one-way rather than interactive communication; a narrow categorical approach to AIDS; a failure to integrate prevention and treatment services; and unwillingness to acknowledge widespread distrust of government, scientists, and health officials; and a focus on individual behavior rather than the social and political factors that shape behavior. To address these obstacles, AIDS educators should identify and strengthen those cultural forces that support prevention while also challenging those that block it. AIDS prevention programs need to be integrated into other programs serving community needs, especially into those grassroots organizations that can raise questions of gender behavior and drug use. While AIDS organizations should help meet the service needs of people with AIDS, they must also play a role in mobilizing communities to demand the resources they need to contain the further spread of the epidemic. Finally, AIDS prevention programs need to be linked to a vision of a better world in which the conditions that have contributed to the rapid spread of HIV infection are addressed and improved. PMID- 2265878 TI - Epidemic in the war zone: AIDS and community survival in New York City. AB - The characteristics and consequences of the AIDS/HIV epidemic in New York City are examined, with special attention to its impact on inner-city communities. The high numbers of AIDS cases are the source of increasing stress on public and community treatment and family and neighborhood networks of support. As the epidemic deepens (8 to 10 thousand new cases per year are expected by 1992) these resources, already weakened by years of underfunding, are becoming overwhelmed and are in danger of collapse. The high rates of HIV infection in these communities (5 to 20 percent of adults aged 25 to 45) and their linkage to widespread drug use prefigure the development of endemic levels in several population subgroups, with substantial risk of heterosexual spread. Simultaneously, there is a steady diffusion of infection to adjacent urban areas and, via migration patterns, to localities quite distant from New York City (e.g., Puerto Rico). Some hope can be found in the advent of more effective methods of early intervention for presymptomatic HIV infection. These offer an opportunity for combining clinical care with public health strategies that may restrict the spread of HIV while providing humane care for large numbers of people with AIDS and support for their families. PMID- 2265879 TI - Pediatric AIDS in the United States: epidemiological reality versus government policy. AB - Pediatric AIDS cases constitute approximately 2 percent of total AIDS cases in the United States, but HIV infection and AIDS among children pose a growing concern. Government policies have failed to match the epidemiological reality of the disease. The powerful shapers of public opinion have dedicated their energies to a handful of cases, involving the school attendance of primarily middle-class children. Unfortunately, coverage of school placement issues has overshadowed both the demographically more serious issue of perinatally transmitted AIDS cases and the growing concern over adolescent AIDS. Seventy-five percent of perinatal AIDS sufferers are poor, urban minorities: the disease is clearly related to other indicators of poor child health--urban poverty and oppressive social conditions. School-based prevention efforts for adolescents have been rendered impotent because of moralistic obstacles to explicit education. Prevention of perinatal and adolescent HIV transmission must be both sensitive and relevant to communities in which the greatest threat to survival is poverty, not AIDS. Ultimately, issues surrounding pediatric AIDS only reinforce the long-term position of child health advocates: the best investment a society can make is a sincere commitment of resources to improve the health, education, and welfare of its children. PMID- 2265880 TI - Generational equity and the politics of the welfare state. AB - The concept of generational equity--that the nation is squandering its wealth on entitlements to the elderly while children remain impoverished--has received considerable media attention. The author traces the source of that message to an organization, Americans for Generational Equity, which is dedicated to restructuring the Social Security system along the lines of a social assistance program: reduced benefits available at later ages only to those who qualify through means tests. The impact of this agenda would be to increase the labor force participation of older people, particularly women and minorities, those presently without private pension coverage and already heavily represented in that sector of the economy where labor shortage is developing. Defining national spending priorities in terms of intergenerational conflict obscures the fact that Social Security is the only U.S. welfare program that has been successful in reducing poverty levels. PMID- 2265881 TI - The construction of elder abuse as a social problem: a Canadian perspective. AB - This article uses the social constructionist approach to social problems as claims-making activities and Blumer's theory of the developmental stages of social problems to analyze how elder abuse has been constructed as a social problem in Canada and how interest groups have been mobilized to deal with the alleged problem. Clearly, elder abuse has emerged as a social problem (often under the family violence rubric) and has received some legitimation from professional groups and representatives of government. Efforts to mobilize social action against elder abuse at a national level and to develop legislation and other policy initiatives have, however, so far met with mixed success. While elder abuse has been trumpeted by some claims-makers as a major new form of family violence, the absence of a strong elder lobby group and the absence of developed ideologies (e.g., feminism in the case of wife abuse and child sexual abuse) have resulted in elder abuse receiving much less attention than other problems grouped under the family violence rubric. Indeed, most of the legislation that presently exists in Canada deals not with the abuse of the elderly as a class but with the provision of services to dependent, incompetent adults whether they are elderly or not. PMID- 2265882 TI - The political economy of health care for elderly blacks. AB - The author analyzes the influences of race and class on the life chances of blacks by focusing on the health care of black elderly. Theories based on cultural, class, and racial forces are explained in the context of how each would be used to analyze the health care of older blacks. The lower health and socioeconomic statuses of older blacks compared with older whites are documented. The author argues that cultural factors are unable to explain those differences adequately, and that class factors such as the profit orientation of the medical care system, and race factors such as residential segregation and racial discrimination in the medical care system, both contribute to the disparities in medical care. Since proposals for a U.S. national health insurance or national health service fail to include race-conscious measures, the proposals will fail to eliminate existing racial disparities in the health and health care of the elderly. PMID- 2265883 TI - Dependency among Third World elderly: a need for new direction in the nineties. AB - The current political economy of aging focuses largely on the conditions of old people in Western industrialized societies. Thus it ignores more than half of the world's elderly--those residing in Third World countries. In the first part of this article the author examines aging trends in developing countries, considering recent approaches to addressing the deteriorating economic and social conditions that shape the lives of the elderly in these countries. In the second part, a feminist perspective is used to assess the implications of these demographic trends and development strategies for women in Third World countries. It is argued that policies that place primary responsibility for care of the elderly within families are as unjust in Third World societies as they are in industrialized nations. PMID- 2265884 TI - Anesthesia and mental illness. AB - Although drug interaction probably remains the most potentially serious problem, current evidence suggests that psychiatric medication need not be discontinued prior to anesthesia and surgery, discontinuation of medication may constitute its own hazards. Most interactions can be predicted and appropriate precautions taken, the use of meperidine is now absolutely contraindicated for patients receiving MAOI's. PMID- 2265885 TI - Follow-up of psychiatric comorbidity in the general hospital. AB - Although appropriate follow-up is an important task in the consultation setting, little attention has been directed to its frequency, or the risk profile for minimal or maximal follow-up. Eight hundred twenty-three patients from 1983 to 1986 were examined at the Mount Sinai Hospital using a computerized psychiatric consultation database that recorded demographic information, reason for referral, DSM-III 5 Axes diagnosis, recommendations and number of follow-up interviews. Forty-two percent of the consultations had three or less (minimum) follow-up visits. The minimum follow-up group were significantly less often referred for depression or diagnosed as depression (p = .01), had fewer psychosocial stressors (Axis III) (p = .03), and recommendations for psychosocial treatment by the psychiatric consultant (p = .0001), but had significantly more personality disorders (Axis II) (p = .04). Sixty-two percent of the consultation patients were correctly classified into the follow-up groups by the variables: 1) marital status; 2) living situation; 3) problem assessed as chronic illness or pain; 4) absence of an Axis I diagnosis or diagnostic uncertainty; and 5) number of recommendations by the consultant. PMID- 2265886 TI - Taking care of culturally different and non-English speaking patients. AB - Many physicians evaluate and care for non-English speaking patients and patients from different cultures. If not carefully considered, cultural factors, including language, often interfere with optimal diagnosis and treatment of these patients. In addition to improved clinical care, increased awareness and assessment of these issues will often enhance patient and family satisfaction and cooperation with therapeutic recommendations. A number of cultural examples are given to illustrate various points, which of course cannot be comprehensive, but which should alert the physician for areas to focus upon. The knowledge and skills to perform a sociocultural differential diagnosis and to initiate treatments in these areas are especially important for consultation-liaison psychiatrists. PMID- 2265887 TI - Self-report symptoms that predict major depression in patients with prominent physical symptoms. AB - The diagnosis of depression in patients presenting with both depressive and physical symptoms is potentially confounded and problematic. The present study of 271 patients with four types of illness all with prominent physical symptoms--end stage renal disease (n = 99), irritable bowel syndrome (n = 21), post-infectious neuromyasthenia (n = 25) and eating disorders (n = 126)--investigates if there are a group of symptoms on the Beck Depression Inventory (BDI) which predict the diagnosis of major depressive episode (MDE) made using the Diagnostic Interview Schedule (DIS). Discriminant function analysis of BDI responses yielded a four item function--self-hate, indecisiveness, loss of appetite and suicidal thoughts- which maximally discriminated between patients with and without a current MDE and correctly classified 75 percent of subjects. PMID- 2265888 TI - Screening for depression in primary care clinics: the CES-D and the BDI. AB - The present study was undertaken to examine the utility of the Center for Epidemiological Studies-Depression (CES-D) scale and the Beck Depression Inventory (BDI) as screening instruments for primary care clinic patients. We examined: 1) patients' willingness to complete the scales; 2) the level of agreement between the screening instruments and DSM-III diagnosis of Major Depressive Episode, based on the NIMH Diagnostic Interview Schedule (DIS); 3) the effect on detection rates of raising the cut-off score for each depression screen; and 4) the factor structure of the CES-D in our primary care sample versus findings from general population studies. The CES-D and BDI performed comparably as depression screening instruments. Both produced too many false positives when standard (low) cut-off scores were applied. However, when straight cut-off scores were used, results suggested that either the CES-D or BDI might assist physicians in reliably detecting depressed patients, without an overload of false positives. Comparison of our findings with those from other studies suggest that depression screening instruments may be particularly helpful with older primary care patients. The CES-D factor analysis highlights the need to look more closely at the relevance of positive affect to the detection, diagnosis, and treatment of depressive disorders in primary care practices. PMID- 2265889 TI - Beta-endorphin decline in late luteal phase dysphoric disorder. AB - The beta-endorphin hypothesis of late luteal phase dysphoric disorder (premenstrual syndrome or L2D2) was tested. Twenty-two PMS patients were compared to twenty-two controls. Levels of beta-endorphin, ACTH, FSH, LH, cortisol, prolactin and TRH were measured on the first and twentieth days after menses. PMS subjects exhibited a significantly greater drop in the opiate, beta-endorphin, (p less than .001) than controls. No relationship or significant e was seen with the other hormones/transmitters tested. The symptoms of PMS may be due to noradrenergic rebound following beta-endorphin decline. Symptomatic and pharmacological morphine withdrawal and manic phase of bipolar disorder are discussed as possible models for L2D2. PMID- 2265890 TI - Psychopathologic features among drug addicts and homosexuals with HIV infection. AB - Personal and familial psychopathological histories and information about early losses were collected and the results of the locus of control test and tests for psychological responses were determined for a series of ninety-two HIV-infected subjects (58 drug addicts; 26 homosexuals; 8 heterosexuals, partners of drug addicts). A higher percentage of drug addicts reported past histories of attempted suicide than the homosexuals. Early loss events were more frequent for homosexuals than for drug addicts. There was a higher psychopathological risk for asymptomatic HIV seropositivity in homosexuals, drug addicts who had attempted suicide, subjects that acknowledged that they have serious illness and subjects with external coping mechanisms rather than internal. PMID- 2265891 TI - Methodological issues in the study of personality and psychiatric state in rheumatoid arthritis. AB - Many studies of personality and psychiatric state among patients with rheumatoid arthritis (RA) suffer from methodological weaknesses. This review considers these weaknesses, and suggests criteria that should be met for the sound design of studies that are intended to demonstrate a role for personality traits and psychiatric states in the aetiology and course of the disease. These criteria include the method used to diagnose RA, sample size, the appropriateness of the tests of personality and psychiatric state for use with RA, and the matching of RA subjects with controls. PMID- 2265892 TI - Psychoimmunology and rheumatoid arthritis: concepts and methodologies. AB - The recent growth of knowledge about the immune-neuroendocrine network has important implications for future research into psychosomatic hypotheses about the aetiology of rheumatoid arthritis. The available evidence suggests that three phases of the aetiological process in rheumatoid arthritis need to be considered separately because of the different role that psychological and social variables may play at different points of the disease. These are the loss of immunological tolerance, the onset of joint inflammation and the long-term disease course. It is suggested that future studies will need to be prospective, include multiple sampling techniques and comparisons within patient groups if they are to elucidate the precise role of psychoneuroimmunological factors in rheumatoid arthritis. PMID- 2265893 TI - Is there a cognitive marker in major depression? AB - The purpose of this study was to compare adolescents' response pattern on specific visual tasks during acute and recovered states of depression. Twenty three inpatient adolescents with unipolar depression were tested before and four weeks after treatment. Twenty control subjects matched in age, sex, handedness, and intelligence were tested at similar intervals. Measures included four visual spatial tasks: the Gestalt Street Completion Test, the Judgment of Line Orientation, the Hooper Visual Organization Test and the Rey-Osterrieth Complex Figure. Overall, the results indicated that depressed adolescents performed significantly more poorly than controls in all four measures during both pre-and posttest conditions. They demonstrated greatest difficulty in measures of Gestalt Closure and Judgment of Line Orientation. However, the Gestalt Closure task was the only one to be correlated to severity of depression. These findings are discussed in the light of previous research suggesting a right hemisphere dysfunction and the existence of a cognitive marker in affective disorders. PMID- 2265894 TI - Alzheimer's disease: clinical and pathological characteristics. PMID- 2265895 TI - Misincorporation of uracil into DNA as possible contributor to neuronal aging and abiotrophy. AB - Neuronal aging and abiotrophy may be related to the abnormal presence of uracil in DNA. Evidence which could support this hypothesis exists: 1) DNA polymerase beta, the only nuclear DNA polymerase present in adult neurons which is able to repair damaged DNA, incorporates dUTP or dTTP with the same efficiency. This suggests that in adult neurons the incorporation of dUTP into DNA is solely dependent on the relative intracellular concentration of dUTP; 2) uracil into DNA also arises from cytosine deamination; 3) at birth, when neurons stop proliferating, uracil DNA-glycosylase, the enzyme responsible of the removal of uracil from DNA, nearly disappears; 4) a significant replacement of thymine by uracil in DNA could produce genetic instability which in turn could affect the recognition of DNA sequences by enzymes and/or by regulatory DNA binding proteins. Thus enzymatic defects which might alter the intracellular dUTP pool, in different neuronal systems, could account for the multiplicity of the clinical manifestations of aging and neurodegenerative disorders. The increase of the age specific rate of abiotrophic diseases may be due to accumulation with time of uracil containing DNA. PMID- 2265896 TI - Visually guided behavior of monkeys after early binocular visual deprivation. AB - Four infant monkeys were binocularly deprived of vision through their first year of life. After the end of the deprivation their visually guided behavior was followed for one year. Behavioral tests were performed to assess their visual functions. The performance of the deprived monkeys was compared with the performance of three normally sighted monkeys. The following functions were tested: the monkey's ability to detect a moving light spot, to track a moving object, to grasp an object, to chatter the teeth in response to a threatening face, to pick pellets from a board, to respond to a sudden visual threat and to move about in a wide space. The visually deprived monkeys remained severely visually handicapped. They were able to detect a moving light spot in a darkened room and to recognize the movement of large objects. However, they continued bumping into objects and used tactile exploration when moving about in a wide space. They never learned to respond to a threatening face, which for a normal monkey is part of the normal behavioral repertoires. The persistently poor visually guided behavior of these monkeys is in agreement with the electrophysiological findings in the posterior parietal association cortex of these monkeys; early visual deprivation permanently reduces the number of visually responsive cell groups in this association area. PMID- 2265897 TI - Paw preference in cats: distribution and sex differences. AB - Paw preference assessed by a food-reaching test was studied in male and female cats. Of the total sample (N = 66), 34 (51.5%) were right-preferent, 24 (36.4%) left-preferent, and 8 (12.1%) ambilateral. In the total sample, there was evidence for an overall paw preference, general paw preference, right-, and left paw preference. The distribution of the right- minus left-paw reaches was neither normal, nor U or J shaped. Of the males (N = 24), 10 (41.7%) were right-pawed, 12 (50.5%) left-pawed, and 2 (8.3%) ambilateral. In males, there was evidence for an overall, general, and right-, left-paw preference relative to no preference. The right- minus left-paw reaches fitted to guassian data with two prominent peaks due to the right- and left-preferents. In females (N = 42), 22 (52.4%) were right preferent, 14 (33.3%) left-preferent, and 6 (14.3%) ambilateral. There was an overall, general, and right-preference but not a left-preference relative to no preference. The distribution of the right- minus left-paw reaches was neither normal nor U or J shaped. The female right-preferents showed a right-bias compared to males. The left-preferent males were more left-preferent than the right-preferent males are right preferent. The mean right- minus left- paw reaches for the female right-preferents were significantly higher than those for the male right-preferents. There was no significant difference between the right- minus left-paw reaches of the male and female left-preferents. The paw preferences exhibited consistency over time; no learning tendencies were established during testing periods for at least 10 days. Considering the mean right-paw reaches for each successive day (N = 10), the mean right-paw uses in the right-preferents was higher in females than males. The mean left-paw uses in left-preferents was about the same for males and females. In males, the mean left paw uses for the left-pawed males were higher than the right-paw reaches for the male right-preferents. In females, there was no difference between the right paw reaches of the right-preferents and the left-paw reaches of the left-preferents. It was concluded that there is a right-bias in paw preference of cats, which is caused by the female right-preferents under the influence of a biological factor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2265898 TI - Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis. AB - Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation. PMID- 2265899 TI - Mood-dependent fluctuations in the severity of tardive dyskinesia and psoriasis vulgaris in a patient with schizoaffective disorder: possible role of melatonin. AB - There is evidence that patients with affective disorders are at high risk for developing Tardive dyskinesia (TD). In addition, in patients with bipolar illness, depressive episodes have been associated with exacerbation of the TD, while manic episodes were accompanied by attenuation of TD. Since depression is associated with diminished melatonin secretion, the high incidence of TD in patients with history of depression may be linked to diminished secretory activity of the pineal melatonin. We report a 28-year old female patient with schizoaffective disorder associated with psoriasis vulgaris in whom periodic exacerbation of depressive moods and suicidal thoughts were accompanied by worsening of the TD as well as the psoriatic lesions. Spontaneous improvements of mood were associated with disappearance of the involuntary movements and regression of the psoriatic lesions. Since melatonin secretion is diminished in patients with depression and in patients with psoriasis vulgaris, this report may add further support to the hypothesis that the development of TD may be associated with diminished secretory activity of pineal melatonin. The mechanisms by which diminished melatonin secretion may facilitate the emergence of TD are discussed. In addition, the possibility that light therapy, as has been successfully used in the management of seasonal affective disorders, may be useful in the management and perhaps prophylaxis of TD is discussed. PMID- 2265900 TI - Increased incidence of neuroleptic-induced perioral movements in the rat by hyperglycemia. AB - It has been suggested that Tardive dyskinesia (TD) is associated with abnormal glucose metabolism. To investigate further the issue the effects of alloxan induced hyperglycemia on the incidence and severity of haloperidol-induced perioral movements were studied in the rat. Hyperglycemic rats showed significantly higher incidence and severity of rating of abnormal perioral movements than did control rats. Severity ratings of perioral movements were significantly correlated with blood glucose levels in the hyperglycemic rats. These findings suggest that hyperglycemia may increase the severity of neuroleptic-induced perioral movements, and support the possibility that glucose intolerance may increase the risk of TD. PMID- 2265901 TI - Brainstem evoked potentials in learning disabled children. AB - Averaged brainstem auditory responses (BAER) were recorded using left and right ear stimulation with clicks of 90 dBs in two groups of primary school children (control and learning disabled). A linear multiple regression model was used in an attempt to demonstrate the effects of sex, high risk factors related to brain damage and learning disability on the evoked responses. Sex showed a strong influence in the latencies of the first five peaks, with girls having shorter latencies. Risk factors had an effect on the latency of peak V, the I-V interval and the V/I amplitude ration, but only when the left ear was stimulated. Learning disability had no significant influence according to this analysis. Multivariate test of complete homogeneity showed highly significant differences between LD and control boys when the left ear was stimulated and between control and LD girls when the right ear was stimulated. Principal component analyses revealed differences between the two groups: the BAER components of the control subjects showed a minor source of variance when the right ear was stimulated. A contrary effect was observed in LD children. Such differences might be related to ear preference and hemispheric dominance. PMID- 2265902 TI - Anterograde memory for visuospatial arrays. AB - A new test was developed to assess direction of errors and hemispatial differences in anterograde memory for visuospatial arrays of abstract figures. After a series of learning trials, delayed recall of figure placement was obtained in 12 healthy dextral adults. Horizontal and vertical errors were measured for each figure. Mean directional error and mean absolute error were calculated for each subject in left and right hemispace for horizontal and vertical dimensions. Although no hemispatial effect was found for mean absolute error, hemispatial differences were present for mean directional error in both horizontal and vertical dimensions. Overall, horizontal deviations were medial, and vertical deviations were downward. However, these effects reached statistical significance only in right hemispace. The directional errors are believed to be due to an attentional shift toward proximal peripersonal space, in combination with attentional shifts from differential left/right cerebral activation. PMID- 2265903 TI - The effects of visual field size on hemispheric asymmetry of pattern reversal visual evoked potentials. AB - Visual evoked potentials (VEPs) were recorded in 17 females (10 right-handers and 7 left-handers) and 17 males (10 right-handers and 7 left-handers). The stimulus was a checkerboard pattern phase-reversed at a rate of 1 Hz, binocularly viewed by the subject. Two experimental conditions were tested: field size (the stimulus was enlarged from 1 to 30 degrees of visual angle) and occlusion (the central part of the stimulus was occluded by experimental scotomata of various size--from 1 to 16 degrees). Responses recorded at occipital and temporal leads of the two hemispheres were compared. The P100-N145 amplitude was larger at occipital than at temporal leads, it augmented increasing the size of the stimulus and diminished occluding progressively larger portions of the central field. Hemispheric asymmetries emerged with large field sizes and were not abolished by the presence of experimental scotomata. The hemispheric asymmetry was related to handedness (left-handers had larger amplitudes in the right hemisphere, right handers in the left hemisphere), but not to sex. Hemispheric asymmetries in VEPs latency were not present. In comparison to males, females showed larger amplitudes and shorter latencies. These results point out that hemispheric asymmetries are found also for the processing of elementary visual stimuli like checkerboards, and they depend both on stimulus parameters (field size) and subject variables (handedness). PMID- 2265904 TI - Movement-related cortical potentials: their relationship to the laterality, complexity and learning of a movement. AB - Movement-related cortical potentials (MRCPs) to self-paced unilateral movements of different laterality, complexity and practice level were recorded from 14 healthy subjects using the EMG onset as the trigger. The amplitudes at certain time points and slopes of linear regression lines fitted to 3 main shifts have been evaluated. In the early phase of MRCP the potential and slope values were symmetrically distributed around the midline maximum, which indicates that this part of MRCP can not originate from the primary motor area, which is in a contralateral relation with the movement, but from secondary motor areas (SMA and premotor areas). The changes in the voltage levels and slopes of this phase due to the changes in laterality, complexity and practice level of the movement show the relation of this activity with the abstract characteristics of the movement. The decrease of voltages and slope values in the later phases of MRCP in the complex task, which is replaced by higher voltages and slopes after a certain learning period was evaluated as a result of inhibition of associative movements via reafferent feedback signals occurring often in the first stages of learning period. PMID- 2265905 TI - Neurobehavioral hemispheric preferences: a case of sexual dimorphism. AB - Ninety subjects (47 females and 43 males) with age ranging from 17 to 25 completed a neurobehavioral inventory of hemispheric preference. The inventory (Wagner & Wells, 1985) consists of 12 items, each of which has 4 statements that relate to four different functions of the two hemispheres namely: (a) Left logical (b) Left-verbal (c) Right-manipulative/spatial and (d) Right-creative. The results indicated an overall preference for verbal-logical tasks. This preference pattern was more pronounced in males than in the female subjects. Also, the female subjects exhibited greater preference for creative tasks (activities), whereas the males showed preference for verbal tasks. These results suggests that proficiency and preference may not necessarily follow the similar pattern. PMID- 2265906 TI - There is a close relationship between hand skill and the excitability of motor neurons innervating the postural soleus muscle in left-handed subjects. AB - The claim that there is not a consistent inhibition of the H-reflex from the dominant leg was examined and rejected. It was re-established that there is an inverse relationship between hand skill and the excitability of motoneurons innervating the postural soleus muscle in left-handed subjects. In left-handers with significantly better left-hand skill, the height of the H-reflex recovery curve was significantly higher on the right leg (nondominant) than the left leg (dominant). There was a positive linear correlation between the asymmetries of hand skill greater than zero (better left-hand skill) and the H-reflex recovery curves from the right and left legs greater than zero (right dominance in reflex excitability). In left-handers with no significant difference between the right- and left-hand skills, there was no significant difference between the mean recovery curves from the right and left legs for the interstimulus intervals from 40 to 100 ms; the height of the left recovery curve was found to be significantly higher than the height of the right recovery curve for the interstimulus intervals from 150 to 1000 ms. It was concluded that there is close relationship between hand skill and motoneuronal excitability from right and left soleus muscle with regard to support and operative functions of legs in left-handers. PMID- 2265907 TI - The effect of task difficulty upon the extent to which performance benefits from between-hemisphere division of inputs. AB - The means by which the two hemispheres coordinate processing of information are not well understood. By means of a tachistoscopic paradigm, we have shown repeatedly that performance is better when two conflicting tasks are presented to separate hemispheres than when both tasks are presented to a single hemisphere. The present study examines whether this effect is restricted to a specific range of task difficulty. Adult right-handers viewed two conflicting naming tasks by means of a tachistoscope. Task difficulty was lowered by reducing processing load (Experiment I: N = 32). Task difficulty was raised by projecting a visual mask 40 ms after offset of the visual displays (Experiment II: N = 10). At lower levels of processing load, dividing conflicting tasks between the hemispheres was beneficial, but not significantly so. At higher levels of load, and at either higher or lower loads with a visual mask, there were significant benefits associated with dividing conflicting tasks between the hemispheres. Three alternative explanations are discussed for the absence of an advantage associated with between-hemisphere division of inputs when task difficulty is reduced. PMID- 2265908 TI - The molecular mode of brain mRNA processing damage followed by the suppression of post-transcriptional poly(A) synthesis with cordycepin. AB - Complete suppression of polyadenylation of nuclear precursors of rat brain mRNA by cordycepin leads to degradation of some translatable sequences of both poly(A)(+)- and poly(A)- pre-mRNA localized in 80S hnRNP-particles. This fact has been established by comparative analysis of the data of two-dimensional gel electrophoretic mapping of translation products synthesized in reticulocytic cell free system using the exogenous purified templates of rapidly labelling translatable 9-17S hn RNA (pre-mRNA) isolated from brain 80S hn RNP particles of experimental (4 hrs after cordycepin injection) and control (injection of physiological solution) adult healthy male rats. Long contact of brain cells with cordycepin (4 or more hrs) creates conditions for formation of hnRNP-particles devoid of poly(A)+ RNA and poly(A)-binding proteins. These particles differ from "normal" ones by the value of the RNA/protein ratio, and by considerably lower resistance to the action of exogenous ribonucleases and endogenous RNase. Cordycepin does not have a direct effect on biosynthesis of nuclear poly(A) binding proteins within the duration of the experiment (8 hrs). The phenomena described are discussed. PMID- 2265909 TI - The construct validity of the Four Word Short-Term Memory Test: a preliminary study. AB - Recent research with the Four Word Short-Term Memory Test (STMT) has suggested that it may provide information useful in the clinical setting. The present study evaluated the construct validity of the STMT. Twenty subjects were administered the STMT in addition to the Wechsler Adult Intelligence Scale and the Wechsler Memory Scale. As expected, performance on the STMT was significantly correlated with both Memory Quotient and Verbal Intelligence Quotient. A stepwise linear regression analysis suggested a trend toward significance for the relationship between the STMT and MQ, after accounting for the influence of Verbal Intelligence Quotient. The data suggest the need for a verbal intelligence correction when using the STMT clinically. PMID- 2265910 TI - Pineal melatonin functions and the depression of Parkinson's disease: a hypothesis. PMID- 2265911 TI - Relationship between the Category Test and the Picture Arrangement subtest of the WAIS-R. AB - Research with the Halstead Category Test has suggested that the test measures the ability of the individual to plan ahead and exercise judgment. Likewise, the Picture Arrangement subtest of the WAIS-R has been viewed as a measure of planning ability. It was hypothesized that scores on the Category Test and Picture Arrangement subtest would be significantly negatively related given their common assessment of planning ability. Scores on these two measures were examined for 71 case examples presented by Golden, Osmon, Moses and Berg (1981). Partial correlation analyses were performed controlling for age, level of education, and Performance IQ scores. The results indicated that once age, education, and Performance IQ scores were controlled for, the correlation between Category Test errors and Picture Arrangement subtest scores only approached significance. The results of this study suggest that the two measures may assess different cognitive processes. PMID- 2265912 TI - The predictive validity of a neuropsychological screening measure. AB - This study examined the efficacy of a neuropsychological screening measure in discriminating between neurologically impaired and nonimpaired subjects. It also examined the ability of this screening measure correctly to classify impaired subjects according to right and left hemisphere involvement. The results showed that some 96% of subjects could be correctly classified as impaired or nonimpaired. The measure was also found correctly to identify the hemisphere involved in 95% of the impaired cases. The value and limitations of neuropsychological screening instruments was discussed in terms of portability and ease of administration. PMID- 2265913 TI - Eyeblink frequency, rehearsal activity, and sympathetic arousal. AB - Previous studies have suggested that the endogenous eyeblink rate (EBR) is inhibited by visual attention and increased by sympathetic arousal as well as by verbalization. As for the latter variable, it has been suggested that verbalization increases EBR by spreading of electric activity in efferent adjacent vocal and eye-motor pathways. The present study was designed in order to examine whether subvocal ("rehearsal") activity also elicits an increase in EBR. Subjects saw slides depicting either verbal or pictorial information. Subsequently, they were asked to rehearse this information silently. Spontaneous electrodermal fluctuations (SFs) were monitored throughout the experiment. The results clearly show that slide presentation ("information uptake") is accompanied by decrease in EBR, while silent rehearsal of information is accompanied by increase in EBR. Furthermore, this increase in EBR was found to correlate positively with SFs. Thus, results confirm the modulatory influences of visual attention, arousal and (sub)vocal activity on EBR. Furthermore, they suggest an explanation for the relationship that has been found between depressive mood and increased EBR. That is, heightened EBR in depression may reflect subvocal activity ("rumination"). PMID- 2265915 TI - The significance of eye blink rate in parkinsonism: a hypothesis. AB - Alterations in blink rate have been reported in several neuropsychiatric disorders presumed to result from abnormal central dopaminergic functions. Increased blink rate in schizophrenia, Tardive dyskinesia, Tourette's syndrome and Meige's disease are associated with enhanced dopaminergic functions. Parkinson's disease is associated with reduced dopaminergic functions and decreased blink rate. Thus, blink rate may reflect striatal and mesolimbic dopaminergic activity. Since acute light exposure suppresses melatonin production and darkness stimulates melatonin secretion, blinking may serve to regulate light dark exposure to the pineal gland and thus to 'fine tune' melatonin production. As there is evidence to suggest that melatonin inhibits the release of dopamine in the striatum and limbic system, increased blink rate may serve to reduce light exposure, increase melatonin secretion and attenuate dopaminergic functions. Conversely, decreased blinking (as is observed in patients with Parkinson's disease) could reflect a compensatory mechanism to increase light exposure, reduce melatonin production and ultimately increase dopamine functions. This model is novel in that for the first time it suggests a functional link among blink rate, melatonin secretion and striatal dopaminergic functions in movement disorders. PMID- 2265914 TI - Visuospatial orientation in Parkinson's disease. AB - Visuospatial functioning in patients with Parkinson's disease was investigated using neuropsychological measures of basic visual perception, complex perceptual discrimination, and spatial orientation. Three subgroups of patients were described: (a) those with broadly impaired visuospatial abilities, (b) those with generally intact abilities, and (c) those whose performance on a task of spatial orientation was lower than their performance on a task of complex perceptual discrimination. These subgroup differences were also concordant with three other variables: age, duration of disease, and degree of dementia. It is suggested that decreases in spatial orientation functioning in Parkinson's disease may reflect the speed of progression of this disease. PMID- 2265916 TI - Effects of characterological anxiety and situational arousal on the solving of a color-word interference task: hemispheric processing implications. AB - Stroop color-word stimuli permit examination of relative hemispheric contributions to cognition. Subjects of varying trait anxiety levels underwent situational arousal manipulations. Discrete color-word stimuli were projected to the visual half-fields; motor matching responses were made. Trait anxiety affected left-hemisphere activation. Responding was faster and more accurate for moderate than low trait anxiety; at high levels, the left hemisphere became overactivated and inefficient. Situational arousal facilitated right-hemisphere performance; latencies were shorter and accuracy increased in the aroused compared with the relaxed condition. Situational arousal interacted with trait anxiety; highly trait-anxious subjects had longer latencies and decreased accuracy when relaxed than when aroused. A paradoxical effect of trait anxiety is rigidity and stereotypy of cognitive functioning, impairing ability to assume appropriate alternative cognitive modes. PMID- 2265917 TI - The pineal gland and the mechanisms of tardive dyskinesia. PMID- 2265919 TI - Response persistence of cat retinal ganglion cells to the temporally discrete presentation of sinewave gratings. AB - The neural basis of visible persistence is not well understood. In the present study the initial onset responses of cat retinal ganglion cells to the abrupt onset and offset of sinewave gratings were examined to determine if ganglion cells display a degree of response persistence that might account for the phenomenon of visible persistence. The responses of X and Y ganglion cell axons were tested using single-unit extracellular recording techniques. Both cell types displayed some degree of response persistence and over a limited range of short stimulus durations response persistence was inversely related to stimulus duration. These data suggest that neural persistence at the ganglion cell level may be the initial physiological basis for some types of visible persistence. PMID- 2265918 TI - Sex differences in the functional asymmetry for facial affect perception. AB - Twenty-six right-hand-dominant women and 26 right-hand-dominant men were required to identify the facial affective expression of Ekman and Friesen's (1978) angry, happy, and neutral stimuli using a forced-choice reaction-time paradigm with only angry or happy alternatives signified by the respective response manipulanda. Stimuli were presented within the left or right visual fields to provide additional data on sex differences in the lateralized processing of facial affective stimuli. The results supported the hypothesis of greater laterality among men with equivalent response times for women and men to stimuli within the right but not the left visual fields. Men were significantly faster in processing affective facial information within the left visual field. The results also indicated that differential rates of learning occur in affective tachistoscope tasks for happy and angry stimuli. Thus, opposite conclusions may be derived from procedural differences among studies in the number of identification trials employed. PMID- 2265920 TI - A close relationship between hand skill and the excitability of motor neurons innervating the postural soleus muscle in right-handed female subjects. AB - The claim that there is not a consistent inhibition of the H-reflex from the dominant leg was examined and rejected. Hand preference was assessed by the Edinburgh Inventory, and hand skill by the peg moving task. All the subjects were right-handed in preference and skill. It was re-established that there is an inverse relationship between hand skill and the excitability of motoneurons innervating the postural soleus muscle in right-handed female subjects without familial sinistrality. There was no significant difference between the recovery curves from the right and left sides in subjects with familial sinistrality. The H reflex from right leg was different between these right-handers. There was a positive linear correlation between the asymmetry index of hand skill greater than zero (right-hand dominance) and the asymmetry index for H-reflex recovery curve greater than zero (left dominance in reflex activity). It was concluded that there is a spinal motor asymmetry in postural leg muscles to handedness. PMID- 2265921 TI - Lithium and imipramin effects on paw preference in cats. AB - The effect of lithium and imipramin on paw preference was studied in cats. Paw preference was assessed by the food-reaching test. It was found that lithium decreased, and imipramin increased the asymmetry of paw use. The lithium effect was antagonized by imipramin. It was concluded that paw preference may reflect a biochemical asymmetry in the brain. These effects of these psychoactive drugs may be of importance for the origin and treatment of affective disorders. PMID- 2265922 TI - Subjective and objective sleepiness in the active individual. AB - Eight subjects were kept awake and active overnight in a sleep lab isolated from environmental time cues. Ambulatory EEG and EOG were continuously recorded and sleepiness ratings carried out every two hours as was a short EEG test session with eyes open for 5 min and closed for 2 min. The EEG was subjected to spectral analysis and the EOG was visually scored for slow rolling eye movements (SEM). Intrusions of SEM and of alpha and theta power density during waking, open-eyed activity strongly differentiated between high and low subjective sleepiness (the differentiation was poorer for closed eyes) and the mean intraindividual correlations between subjective and objective sleepiness were very high. Still, the covariation was curvilinear; physiological indices of sleepiness did not occur reliably until subjective perceptions fell between "sleepy" and "extremely sleepy-fighting sleep"; i.e. physiological changes due to sleepiness are not likely to occur until extreme sleepiness is encountered. The results support the notion that ambulatory EEG/EOG changes may be used to quantify sleepiness. PMID- 2265923 TI - Magnetic resonance imaging correlates of internuclear ophthalmoplegia. AB - Internuclear ophthalmoplegia (INO) is a gaze disorder characteristic of lesions involving the medial longitudinal fasciculus (MLF). Two patients aged 62 and 74 years presented with acute neurologic deficits characteristic of INO. Computed axial tomography (CT) did not detect abnormalities in the region of the MLF. Magnetic resonance imaging (MRI) however, demonstrated brainstem hypersignals with long T2 characteristics in the region of the MLF which correlated with the clinical symptoms. These cases illustrate the value of the MRI in evaluation of patients with INO and suggest that MRI is superior to CT in evaluating gaze disorders attributable to brain dysfunction. PMID- 2265924 TI - Differences in neuropsychological performance in psychiatric, anterior- and posterior-cerebral dysfunctioning groups. AB - The neuropsychological performance of psychiatric, anterior- and posterior cerebral dysfunctioning groups was compared using both raw scores and scores statistically adjusted for the effects of age, education, gender, and overall level of intellectual functioning. Between 5% and 37% of the variance of the subtests of the WAIS-R and between 9% and 58% of the variance associated with the neuropsychological variables was accounted for by the demographic variables. Using raw scores, ten of the twenty-five tests showed significant overall differences among the groups, while only five of the contrast using adjusted scores were significant. Anterior- and posterior-cerebral dysfunctioning groups generally were significantly more impaired than the psychiatric group. Memory and problem-solving variables were the most sensitive to the removal of demographic variance, while psychomotor test scores were the most robust. Differences among cerebrally impaired and psychiatric groups may be obscured by demographic variables or levels of general intellectual functioning. PMID- 2265925 TI - Differential patterns of memory loss in patients with Alzheimer's disease and Korsakoff's disease. AB - Patients with Korsakoff's disease or the likely diagnosis of Alzheimer's dementia were tested on various mnemonic tasks and the results compared to the performance of alcoholic or normal controls. The experimental outcome indicates similar perceptual learning processes of Alzheimer and Korsakoff subjects. On the other hand, both groups of patients showed a somewhat different pattern of episodic memory loss, and a different proportion of intrusion and omission errors in the learning of semantically related words. The results are discussed with respect to some neuropathological and neuropsychological sequelae. PMID- 2265926 TI - Possible role of pineal melatonin in the mechanisms of aging. AB - The pineal gland has captured man's attention as early in recorded history as the Greeks when philosophers considered it the "seat of the soul". Descartes, in the Middle Ages, furthered this concept naming it "esprits animaux" or, in current language, the psychic and somatic activating principle. These notions about the pineal gland were initially purely speculative and unsupported by scientific facts. However, with the development of a sound knowledge base concerning the pineal gland over the past twenty years, evidence has accumulated to suggest a pivotal role for the pineal in the 'fine tuning' and integrating of various neural and endocrine functions. The secretion of pineal melatonin has been shown to decline progressively with age. Recent hypotheses of aging have suggested that cumulative neuronal insults associated with free radical production may be associated with the process of aging. There is evidence to suggest that melatonin may protect against the age processes in part by attenuating the effects of free radical-induced neuronal damage. Other studies derived mainly from observations on pinealectomized rats also suggest that diminished melatonin secretion may be associated with acceleration of the aging process. Thus, pineal melatonin may be a natural anti-aging hormone. PMID- 2265927 TI - Responses elicited by species-specific models in the cichlid Crenicichla lepidota (Heckel). AB - Species recognition by the cichlid fish C. lepidota was studied by measuring species-specific aggressive behavior toward either live conspecifics (control) or toward different two-dimensional models. A plain fish-shaped model elicited aggressive behavior, but the responses were mostly absent when the model was a rectangle. Adding heavy stripes to the fish-shaped form increased the responses, which were further enhanced by adding a spot. Comparable aggressive responses were also induced by adding spots and eye to dummies with thin stripes. We conclude that in our experimental conditions, fish-like shape and contrast seem to be of great significance for recognition of conspecifics in the cichlid C. lepidota (Heckel). PMID- 2265928 TI - Neural aging: speculation. AB - This communication attempts to explain the absence of mitosis in cortical neurons of adult mammals in terms of defective proteolysis and a hypothetical proteolysis inhibiting factor (PIF). Highly speculative hypotheses offer an explanation for aging at the cellular level. The speculations are analyzed in terms of Sacher's action principle for mammalian longevity, which is based on encephalization, metabolic rate, and body temperature. PMID- 2265929 TI - Does attention affect the motor programs of pharmacologically induced eye movements? AB - Attention plays an important role in oculomotor function. We studied the effect of attentional stimuli on eye movements induced by ketamine. The experiments were carried out on three monkeys. Ketamine injected intramuscularly induced nystagmus. When we switched on a new stimulus these eye movements stopped and the animal made a saccade toward it. This may be due to a new motor program, triggered by a visual stimulus, that among its characteristics is able to engage the animal's attention. The program of evoked saccade is overwritten on induced oculomotor activity. Our results suggest that attentional processes modify the dynamic characteristics and induce in particular behavioral condition a new motor program. PMID- 2265930 TI - Temporal discrimination in schizophrenic and affective disorders: evidence for a dopamine-dependent internal clock. AB - Performance in temporal discrimination of time intervals in the range of milliseconds was compared in 80 healthy subjects, 27 patients with schizophrenic disorders, 33 patients with major depression, 21 patients with dysthymic disorders. For schizophrenic patients as well as for patients with major depression, pronounced deficits in duration discrimination could be demonstrated as compared to the healthy control group (p less than .01). Patients with dysthymic disorders and schizophrenic patients differed significantly from the melancholic group (p less than .01 and p less than .05, respectively). The results are discussed on the basis of the assumption of an internal clock, implying that the clock rate is highest and therefore temporal resolution is best with healthy subjects. With psychiatric patients performance in temporal discrimination was impaired to a slowing down in clock rate and thus decreased temporal resolution. There is strong evidence that changes in clock rate depend on the effective level of dopamine. This leads to the conclusion that temporal discrimination thresholds may be seen as an indicator for deviations from the optimal level of dopaminergic activity in psychiatric patients. In addition, possible effects due to age and medication are discussed. PMID- 2265931 TI - Relation of hand skill to spatial reasoning in male and female left-handers with left- and right-hand writing. AB - The relation of mental ability for spatial reasoning (Cattell's Culture Fair Intelligence Test) to hand skill assessed by peg-moving task was studied in normal left-handers. Nonlinear, quadratic relationships were established between these two parameters exhibiting different characteristics according to sex and writing hand. It was concluded that the contributions of the right and left cerebral hemispheres to the cognitive-motor output of the brain depend on sex and writing hand as well as the degree of left-handedness in left-handers. PMID- 2265932 TI - Stimulation of 36Cl- permeation in the in----out direction across the Dieters' neuron membrane by GABA on its cytoplasmic side: effect of different ionic conditions. AB - The permeation of labelled Cl- ions across single plasma membranes microdissected from rabbit Deiters' neuron was studied in a microchamber system. In particular, we studied 36Cl- in----out permeation and its stimulation by 10(-6) M GABA on the cytoplasmic side under different ionic conditions on both sides of the membrane. Three main results were found: a) The GABA effect turns up at a cytoplasmic side [Cl-], 21 mM, in the range of the normal steady state intracellular Cl- concentration. It disappears both at tracer level of Cl- on the cytoplasmic side and when [Cl-] is high there (140 mM). b) The increase in ionic strength due to the equinormal substitution of monovalent anions (Cl- and acetate) with the trivalent impermeant anion citrate on both sides of the membrane erases the GABA effect even if Cl- is at the optimal cytoplasmic side concentration, 21 mM. c) Citrate ions reduce to the limit of significance the GABA effect even when they are only on the membrane extracellular side and [Cl-] is at the optimal level on the other side. These results confirm that GABA stimulated Cl- permeation in the in----out direction is via Cl- channels exposing positive charges at their cytoplasmic mouth. In addition, they point out that such GABA activated channels are endowed with a partial electrical positivity at their extracellular exit. PMID- 2265933 TI - Relation of spatial reasoning ability to hand performance in male and female left handers to familial sinistrality and writing hand. AB - The relation of mental ability for spatial reasoning to hand performance was studied in male and female left-handers considering familial sinistrality and writing hand. Hand performance was assessed by a dot-filling test; hand preference was assessed by the Edinburgh Handedness Inventory (Geschwind scores). Nonverbal intelligence (spatial reasoning) was measured by the Cattell's Culture Fair Intelligence Test. The relationship between IQ and hand performance was found to be more complicated than expected. This was associated with sex, familial sinistrality, and writing hand, which created different patterns in interactions between motor and cognitive systems. It was concluded that the brain benefits from different strategies by using both hemispheres in a competitive and complementary manner where necessary to achieve a high visual-spatial performance depending upon genetic preprograms. PMID- 2265934 TI - Relation of testosterone and hand preference in right-handed young adults to sex and familial sinistrality. AB - The relationship between serum testosterone level and the degree of hand preference was studied in right-handed young adults. Hand preference was assessed by the Edinburgh Handedness Inventory. Serum testosterone level was determined using tritium-marked-radioimmunoassay. There was no significant correlation between these variables in males without FS. In males with FS and in females with and without FS, the serum testosterone levels were found to be negatively linearly correlated with the degree of the right-hand preference. Similar results were obtained with respect to foot and eye preferences. It was concluded that not only prenatal testosterone but adult testosterone also may exert a life long influence on cerebral lateralization; this effect seems to be much more pronounced in the female than male brain, which may exert a female-like pattern under genetic control. PMID- 2265935 TI - The role of periaqueductal gray in mediation of analgesia produced by different frequencies electroacupuncture stimulation in rats. AB - The marked suppression of noxious heat-evoked tail flick reflex was produced in conscious rats by low (2 Hz) or high (100 Hz) frequency electroacupuncture (EA) stimulation at acupoints S36 and Sp6. Electrolytic and kainate lesions in the ventral periaqueductal gray (vPAG) led to significant attenuation of the low and high frequency EA analgesia as measured 4 and 6 days following the lesion. In sham-operated animals, analgesia induced by either low or high frequency EA remained intact. The role of vPAG in organization of different EA analgesia is discussed in detail. PMID- 2265936 TI - The relationship between the degree of paw preference and excitability of motor neurons innervating foreleg flexors in right- and left-preferent cats. AB - The relationship between the degree of paw preference and the degree of excitability of motor neurons innervating the foreleg flexor muscles was studied in unanesthetized spinal cats. The paw preference was assessed by a food-reaching test. The cats were spinalized at the first cervical segment of the spinal cord. It was found that there is an inverse relationship between the degree of H-reflex excitability and the degree of paw preference in right- and left-preferent cats. This main result was discussed with respect to functional implications and evolution of human handedness. PMID- 2265937 TI - Testosterone and hand skill in right-handed men and women. AB - The relationship between serum testosterone level and hand skill was studied in right-handed young adults. Hand preferences was assessed by the Edinburgh Handedness Inventory. Hand skill was assessed by the peg moving task. Serum testosterone level was determined using tritium-marked-radioimmunoassay. In the total sample, only the right-hand skill showed a direct correlation and an inverse correlation with serum testosterone for men and women, respectively. In male subjects with right-eye preference, both hand skills exhibited a direct relation to serum testosterone. In the total sample, there was a direct and an inverse relationship between the difference in skill between hands and serum testosterone in men and women, respectively. This was, however, affected by right eye and right-foot preference. It was concluded that the serum testosterone in young adults is associated with hand skill exhibiting fundamental differences between men and women; the left cerebral hemisphere seems to be the main target of testosterone. PMID- 2265939 TI - Constraint and pathology in spontaneously activated systems. AB - Neural network modeling is approaching a strange attractor. Mathematical demonstrations of the theoretical behavior of non-Lipschitzian dynamical systems claim to show how such self-developing computational networks may be fully deterministic as to their microstructure yet without any prescription of their final state in advance. Justification for these simulations stems from applications which demand more biological realism in the design of neurobiotics. Realization of such modeling in actual hardware does not exist. While the best of these models are surely heuristic for neuroscientists who want to know how brains work, their attempted realization in control systems for planetary high technology seems confounded by several intractable problems, which, a few years ago, would have interested only neurophilosophers in retirement. PMID- 2265938 TI - Periventricular lucencies on computed tomography in multiple cerebral infarcts: correlation with cerebral blood flow measurements. AB - Forty-nine patients with multiple cerebral infarcts with a mean age of 70.2 years were studied to elucidate the effect of periventricular lucencies (PVLs) on cerebral blood flow (CBF). Patients with multiple cerebral infarcts showed significantly lower mean cortical blood flow (F1) values compared to 15 age matched normal subjects (p less than .01). The mean F1 values were most significantly decreased in severe group of PVLs and moderately decreased in moderate and mild groups (p less than .05 between severe and mild groups); however, no significant differences in mean F1 values were found between severe and moderate groups. Demented patients showed significantly lower F1 values compared to nondemented patients (p less than .001) and normal subjects (p less than .001). There was no significant difference in the degree of PVL between demented and nondemented groups. As well, the mean F1 values were not significantly correlated with either the number of infarcts or ventricular dilatation. These results suggest that PVLs on CT (especially in severe cases of PVLs) may have some role in the reduction of cortical blood flow in patients with multiple cerebral infarcts. PMID- 2265940 TI - The field-by-length effect in word processing: a failure to confirm. AB - It has been shown that the left hemisphere superiority for processing words applies only to long words by Young and Ellis (1985). These authors defined the length as the number of letters. Bruyer and Janlin (1989) compiled supporting evidence by contrasting the number of letters and the physical size of the stimuli: Short words were made as long as "long" words by the use of blank spaces between the letters. In the present study, another control was used: The physical size of the stimuli was manipulated by means of the viewing distance (nearer short words were as long as the long words). Thirty-six subjects were submitted to 720 trials in which two words appeared for 150 ms, one in each visual hemifield. The subject reported the two words in a defined order. The results did not clearly support the previous studies. PMID- 2265941 TI - Validation of the Mini-Mental State Examination. AB - The present study examined the concurrent neuropsychological validity of the Mini Mental State Examination (MMS). In this study the Luria-Nebraska Neuropsychological Battery (LNNB) served as a measure of neuropsychological ability. A sample of 20 patients was all administered the MMS and LNNB. Results demonstrate the highest correlation with the MMS for the LNNB expressive language, arithmetic, writing, motor and tactile scales. PMID- 2265942 TI - Comparison of multiple sclerosis and head trauma patients: a neuropsychological pilot study. AB - This paper reports the comparison of multiple sclerosis and head trauma patients on a battery of neuropsychological tests. Age-matched groups of 4 multiple sclerosis and 4 head trauma patients were administered the Wechsler Adult Intelligence Scale--Revised (WAIS-R), the Weschler Memory Scale (WMS) and Category and Tail Making Tests (TMT) from the Halstead Reitan Neuropsychological Test Battery. Statistically significant results between groups were found on all variables with the strongest difference on the Category test and WMS (p less than .01). The concept of cortical vs. subcortical dementia could be used to explain these differences between groups of multiple sclerosis and head trauma patients. PMID- 2265943 TI - Analgesic nitrous oxide as an investigative and therapeutic agent in psychiatry. PMID- 2265944 TI - Is negative schizophrenia a variant of parkinsonism? PMID- 2265945 TI - Enhancement of heartbeat-related brain potentials through cardiac awareness training. AB - Heartbeat synchronous potentials were found to be sensitive to differences in perceptual accuracy. Since heartbeat perception can be improved using appropriate training procedures, increased ability to perceive cardiac performance should also influence heartbeat-related potentials. In the present study, subjects in either of two groups had to press a button immediately after the occurrence of a heartbeat-feedback tone. Whereas the first group was given acoustical heartbeat feedback throughout the entire training, the second group was provided with tone signals that became fainter during the course of the training phases. The better posttraining performance in heartbeat perception of the group receiving full intensity feedback was also reflected in the evoked potentials. They differed markedly before and after training, especially between 250 to 400 ms (after the EKG-R-wave), the biggest effect being at Fz and F7. The findings are interpreted as the brain electrical reflection of an increased perception susceptibility to a cardiovascular signal occurring at about 200 ms after the R-wave. PMID- 2265946 TI - Time and tiles on the brain. AB - Both the quasicrystalline appearance of mammalian cerebral cortex and the quasiperiodicity of mammalian cerebral compound field potentials (EEG/ERBP) have long been noted. A recent experiment claims to show the eigenvalue spectrum of a quasiperiodic tiling of coupled oscillators in the plane; and this spectrum of resonant frequencies has some analogies with that of mammalian EEG/ERBP. Concurrently, Connectionist literature now admits the significance of internally generated network rhythmicity in Non-Lipschitzian neurodynamics. It may be time to test the hypotheses of: (a) quasi-crystalline icosahedral symmetry of neocortical architectonics and (b) some fractal characteristics of EEG/ERBP under behavioral conditions. PMID- 2265947 TI - Cerebral rhythms and temporal coherence. AB - Some studies of scalp-conducted human EEG show a positive correlation between the temporal coherence of prestimulus activity in the theta, alpha, and beta passbands, on the one hand, and both target probability and subjective self report about good performance, on the other. There remains an important ambiguity in these data: Are these changes in temporal coherence merely a reflection of changes in subjective relaxation, or do they index the timing of neural network convergences to terminal attractors? Other studies of human EEG during temporal conditioning paradigms suggest that the second alternative can be rigorously tested. PMID- 2265948 TI - Restraint stress modulates sensory evoked potentials. AB - The present experiment investigated whether repeated exposure to an acute stressor elicits changes in sensory evoked responses recorded from awake rats. Animals were restrained for four hours per day on each of four consecutive days. Recordings were obtained on the day prior to the first restraint and following the first and fourth day of restraint. Restraint generally resulted in an increase in the amplitude of sensory evoked responses recorded from the medial basal hypothalamus (MBH), dorsal hippocampus (DH), and superior colliculus (SC) without changing any other characteristics of the recording. A persistent increase in the averaged evoked response amplitudes seen on both the first and fourth daily presentation of the stressor indicates that no significant adaptation to the stressor occurred over this time period as measured electrophysiologically. PMID- 2265949 TI - A close relationship exists between hand skill and the excitability of motor neurons innervating the postural soleus muscle in right-handed male subjects. AB - The claim that there is no consistent inhibition of the H-reflex from the dominant leg was examined and rejected. Hand preference was assessed by the Edinburgh Inventory, and hand skill by the peg moving task. It was re-established that there is an inverse relationship between hand skill and the excitability of motoneurons innervating the postural soleus muscle in right-handed subjects without familial sinistrality. There was no significant difference between the recovery curves from the right and left sides in subjects with familial sinistrality. There was a positive linear correlation between the asymmetry index for hand skill greater than zero (right-hand dominance) and the asymmetry index for the H-reflex recovery curve greater than zero (left dominance in motoneuronal excitability). It was concluded that there is indeed a spinal motor asymmetry in postural leg muscles related to handedness. PMID- 2265950 TI - There is an inverse relationship between the reflex size from wrist flexors and paw preference in spinal cats. AB - The relationship between paw preference and reflex size from wrist flexors was studied in spinal cats. Paw preference was assessed by a food-reaching test. The monsynaptic H reflex and the polysynaptic reflexes were recorded from the median or ulnar nerves following stimulation of the same nerves electrically. The mono- and polysynaptic reflexes were found to be significantly larger on the left side than the right side in right-preferent spinal cats and vice versa in left preferent spinal cats. PMID- 2265951 TI - The left brain determines the degree of left-handedness. AB - The contribution of right- and left-hand skills to left-handedness was studied in 42 left-handed male subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was assessed by a peg-moving task; 10 trials were given to each hand. Peg-moving times decreased linearly with each trial (visuomotor learning). Both hands exhibited equal learning capacities. The learning curves were the same for the left-hands of left-handers with and without familial sinistrality (FS). The right-hand of left-handers with FS was found to be slower than that without FS. The right- and left-hand skills and their learning curves were about the same in left-handers with right-hand writing, exhibiting no difference from the left-hand skill and learning curve of left handers with left-hand writing. Right-hand skill decreased linearly as left-hand preference increased from -40 to -100; left-hand skill was not related to hand preference. Right-minus left (R-L) time for peg moving increased linearly with hand preference from -40 to -100. R-L time for peg moving linearly decreased as the right-hand skill increased; the left-hand skill was not associated with R-L time for peg moving. It was concluded that the right hand (left brain) determines left-handedness; the neural structures only on the left side exhibit pronounced plastic changes to genetic and environmental influences in left-handers. PMID- 2265952 TI - Hypnopolygraphic alterations in Attention Deficit Disorder (ADD) children. AB - The sleep pattern of 13 prepubertal children, nonmedicated, rigourously diagnosed as Attention Deficit Disorder (ADD) was recorded for two consecutive nights. Analyses of sleep pattern variables revealed a marked reduction of sleep onset latency (p less than .01), a great number of nocturnal awakenings (p less than .01), and a high increase of Delta sleep percentage (p less than .01) for the ADD children compared to normals. In addition, the two subtypes of the disorder--ADD with hyperactivity (ADD/H) and ADD without hyperactivity (ADD/WO) or ADD undifferentiated--showed distinct hypnopolygraphic correlates. Those ADD/H children had a greater sleep fragmentation and a lesser degree of sleep efficiency. These findings would support the hypothesis that ADD is related to a deficient control of arousal level and, on the other hand, suggest that ADD/H and ADD/WO are different clinical entities. PMID- 2265953 TI - EEG coherence and power during Yogic Flying. AB - Frontal, central and parietal power and coherence of ten subjects practicing the TM-Sidhi technique of Yogic Flying (YF) were compared to that of ten controls who jumped from a seated position to approximate hopping during YF. All movement artifacts were removed before signal analyses. The most significant group differences were seen in the 2.12-second period just before lift-off: the YF subjects '30-32 Hz power, and theta, alpha, and beta (broad band) coherence were significantly higher than those of the controls'. Within the YF group, the first period's 30-32 Hz power and broad-band coherence were significantly higher than those of the two preceding 2.12-s periods, and of the whole YF period. There were no significant within-group differences in the control group. A similar EEG pattern has been reported during the experience of pure consciousness in TM practice, suggesting that the experience of "pure consciousness" underlies successful TM-Sidhi performance. PMID- 2265954 TI - Biomechanics of head injury. AB - The enormous incidence of closed head injury has resulted in employing the field of biomechanics as a means of predicting the site of a lesion, discovering, and understanding the forces acting during cranial impact. This paper indicates that the possibilities associated with trauma-induced lesions include: the establishment of large pressure gradients associated with damage resulting from absolute motion of the brain and its displacement relative to the skull; flexion extension of the upper cervical cord; skull deformation and/or rotational acceleration. Analytical representations, inanimate and cadaver models and, experimental paradigms are presented and their behavioral implications discussed. PMID- 2265955 TI - The brain: a dynamic system tending toward homeostasis. AB - This paper offers a perspective for understanding the brain as a dynamic system, continually compensating for changing events in its environment. In particular, it presents some of the neurophysiological responses to closed head injury, such as seizures and migraines, and the ability to maintain these changes in obviously advantageous noninvasive methods such as thermology and video taped biomechanics. The ultimate question asked is for a reconciliation of the paradoxical deduction that hyperactivity of the nervous system is parallel in the form of measured neural activity to no activity at all. PMID- 2265956 TI - Orotactile sensation, gustation and palatability: a pilot study. AB - The hypothesis that deficits in orotactile sensitivity may affect gustation and palatability is not new. It is supported by animal models employing deafferentation; however, little direct evidence supports the application of the model to humans. Indirect evidence comes from four separate fields: (1) neuroanatomy, (2) physiology, (3) developmental biology, and (4) learning theory. The results of a pilot study with humans provide additional direct evidence that implicates the role of orotactile sensitivity in human gustation. In this pilot study, the oral cavity was topically anesthetized to determine whether gustation would be compromised to a similar extent as orotactile sensitivity. The time course of the degree of anesthesia was determined by prior measurements of oral tactile sensitivity using an oral air-based aesthesiometer. Different concentrations of NaCl-solution were presented to subjects in order to determine gustatory thresholds before and after anesthesia. Analysis of magnitude estimation data indicated that there were statistically significant decreases in gustatory sensitivity after anesthesia. Basic and applied implications of this area of research are discussed. PMID- 2265958 TI - IQ scores, brain waves, frequency response, and damping ratio: a weak mix. PMID- 2265957 TI - Shape, size and relative space position perception in neglect patients. AB - Shape, size and relative position in space perception were tested in 17 right brain damaged (RBD) patients with neglect symptoms, 10 RBD patients without neglect and 11 controls. Simultaneous pair comparison task in free vision was used. Two arrangements of the visual display were used: side by side and top bottom. Neglect patients' performance was comparable to RBD and controls in the shape and size test, but was below the other groups in the relative space position test. The selective failure of neglect patients in the position task did not depend on the spatial arrangement of the visual display, which may indicate a general perceptual deficit, rather than a deficit restricted to the neglect hemifield. PMID- 2265959 TI - Dichotic listening in an aphasic male patient after a subcortical hemorrhage in the left fronto-parietal region. AB - Dichotic listening (DL) performance to consonant-vowel (CV) syllables is reported in an aphasic right-handed male patient. The patient suffered initially from a complete expressive aphasia after an intracerebral hemorrhage caused by the rupture of an arteriovenous malformation (AVM) underlying Broca's area. The patient was tested three times with DL; one week after the hemorrhage, five weeks after, and after at about 6 months. At the first test he could not speak, but understood well. At the second test he uttered one-syllable words, and could answer "yes" and "no" to questions. At the third test he could speak whole sentences, although slow and "stutter-like." Dichotic listening performance showed an almost perfect match with speech recovery. At the first test he showed a left ear advantage which changed to no ear advantage at the second test, and to a right ear advantage at the third test. The overall performance was markedly reduced at the first test, but improved at the following test. It is concluded that dichotic listening may be a valid complement to traditional language assessment procedures after unilateral brain lesions. PMID- 2265960 TI - Correlation between EEG spectral parameters and an educational evaluation. AB - EEG spectral parameters were computed in a group of children with different degrees of difficulty in learning to read and write. For statistical analyses, Z transformed values according to normative age-regression equations were used to control the age effects. Canonical Correlation Analysis between absolute power in different bands and the categories of the educational evaluation (good, regular, poor and very poor) showed that more delta was probably related to a poor evaluation and more alpha in occipital areas to a good one. MONOVA also showed highly significant differences in the absolute power in many leads between children with different evaluations. As children with a poor evaluation very frequently had antecedents of risk factors related to brain damage and were from a low socioeconomic status, and both factors have been shown to affect absolute power, it may be that the differences observed were due to these causes. However, relative power correlated more with the learning problems. Children with minor difficulties, with no antecedents and with good socioeconomic status had more theta in almost all leads than children with a good evaluation and with the same characteristics. Children with a poor, or very poor, evaluation had more delta in left frontal and temporal areas (F3, F7 and T3) which may reflect underlying cerebral dysfunction of these regions directly involved in reading and writing processes. PMID- 2265961 TI - Experimental epilepsy: electrically and chemically induced convulsions modulate experimental allergic encephalomyelitis and other immune inflammatory reactions in the rat. AB - Male Wistar rats were exposed to electroconvulsive shock (ECS) and pentylentetrazol (PTZ) for a period of 38 consecutive days; 21 days before and 17 days after immunization with guinea pig spinal cord in complete Freund's adjuvant (CFA) ECS and PTZ completely prevented the appearance of paralysis and decreased incidence and severity of lesions characteristic of experimental allergic encephalomyelitis, when compared to control sham-shocked and saline-treated rats. Delayed hypersensitivity skin reactions to old tuberculin and inflammatory enlargement of the foot injected with CFA were significantly reduced in ECS rats, but not in PTZ animals. The results indicate that decreased cellular immune responses in rats are due to the electrically and chemically induced experimental epilepsy. The immunoneuroendocrine pathways by which ECS and PTZ suppress the immune inflammations remains to be elucidated. PMID- 2265963 TI - Cognitive dysfunction in myasthenia gravis. AB - The performance of patients with myasthenia gravis (MG) on selective neuropsychological tests was examined to assess the diagnostic applicability of such examinations. Twenty-seven patients with MG and twenty-seven age, sex, and education-matched controls were given a battery of tests designed to assess cognitive functions. The MG group displayed significantly lower scores on Mini mental state test and memory tests. The results indicated that MG patients had cognitive impairment. Results are also discussed with respect to the involvement of cholinergic pathways in the central nervous system. PMID- 2265962 TI - Peculiarities of the polypeptide composition of the morphofunctionally different neurons of the rat brain. AB - The present study was aimed to identify peculiarities of the polypeptide composition in three morphofunctionally different classes of neurons of the rat brainstem: giant multipolar neurons of n. reticularis gigantocellularis, relay sensory neurons of lateral geniculate body and pyramidal neurons of the pyramidal layer of the CA3 - CA4 fields of hippocampus. The method of free hand dissection of neurons and sodium dodecyl sulfate (SDS) slab gel microelectrophoresis in our modifications were used. Polypeptide peculiarities for each class of investigated neurons have been found. Most of these polypeptides belong to the low molecular weight range (8.8-24.3 KD) of the polypeptide spectra and only some of them to the high one (64.6-75.3 KD). PMID- 2265964 TI - Neuropsychological systems deficits and the isomorphism of control. AB - The papers that follow are based on a symposium presented at the Twelfth European Conference of the International Neuropsychological Society held in Antwerp, Belgium between 5-8th July 1989. The symposium, using closed head injury as a vehicle, attempted to overview approaches to the study of systems function and dysfunction. Rather than concentrate on skill and subtest deficit, the papers addressed diffuse, systemic, subcortical effects and disruption of lower integration centers. They addressed the utility of neural network models to develop theory to explain deficits in behavioral integrating systems; the role of systems approaches in better understanding the overlapping clinical subsets of migraine and seizure disorders; the provision of visual examples of lateralized systemic changes associated with closed head injury through infrared thermology and the presentation of an application of biomathematical systems modeling with potent applications for diagnosis and rehabilitation. Finally the papers were discussed in terms of the clinical and philosophical issues. PMID- 2265965 TI - A continuum model of activity waves in layered neuronal networks: a neuropsychology of brainstem seizures. AB - We model and brainstem as two layers of respectively purely excitatory and purely inhibitory cells, with instantaneous synaptic interactions within a layer, but with a variable time delay between the layers. For appropriate values of the connection parameters, this configuration provides an attentional mechanism. As the inhibitory delay increases, input signals are, at first, increasingly amplified and confined spatially. At larger delays, the amplified activity propagates into other regions allowing for spatial summation. The temporal frequency of the amplified activity decreases with increasing delay, but its spatial frequency remains relatively constant. As the delay increases through a critical region, a new regime is reached in which highly amplified activity occurs simultaneously over large areas. This regime exhibits many properties of seizure activity. PMID- 2265966 TI - Lateralized effects of migraine and ANS seizures after closed head injury. AB - Theoretical issues associated with memory, neurocognitive and noradrenergic mechanisms in posttraumatic migraine and dysautonomic complex-partial seizure disorders are reviewed, compared and discussed. Additionally, pretreatment Contingent Negative Variation (CNV) was recorded in a No-GO/GO reaction-time paradigm for 15 normal, and 18 posttraumatic migraine and seizure patients tested not more than three months postinjury. Normals demonstrated that CNV GO and NO-GO responses significantly differed. In both migraine and seizure patients GO and NO GO trials did not differ significantly. In uncontrolled trials, it was noted that B-Blocker administration increased the difference between GO and NO-GO trials for both migraine and seizure patients over midline leads. PMID- 2265967 TI - Medical thermography and its use in posttraumatic cephalagia. AB - The use of infrared thermographic imaging in the diagnosis of human illness is discussed from the point of view of its historical development and its multiple uses to the present time. Future goals for its use are outlined. Several case histories are presented documenting the use of thermography in post traumatic cephalalgia. PMID- 2265968 TI - Association brain systems as apparatus of behavior control involving dominanta and conditioning. AB - The author's major conception concerning the associative brain systems (thalamoparietal and thalamofrontal) as the behavior control system are presented. The participation of association systems in performance of higher brain functions, due to the entrance of the whole information spectrum of biological and signal significance and the presence of neuronal plastic mechanisms, ensures the mechanism for retrieving the whole behavior programs from long-term memory, the ability of short-term storing of behavior programs, and estimation of their adequacy on the ground of dominanta and conditioning mechanisms. PMID- 2265969 TI - Neuropsychological dysfunctions in amyotrophic lateral sclerosis: relation to motor disabilities. AB - A study was undertaken to elucidate the existence of cognitive and memory impairments in patients with amyotrophic lateral sclerosis (ALS) by comparing a group of ALS patients with both nonneurological medical controls (MC) and healthy controls (HC) on neuropsychological tests. We also examined the relationship between the severity of motor disabilities and intellectual impairment. Twenty two ALS patients, 18 MCs and 17 HCs participated. The tests used were the Mini mental state examination (MMS) and the immediate and delayed memory tests. The mean MMS score of the ALS patients was lower than the mean scores of both control groups. In the memory tests, there were significant differences between the ALS group and the two control groups. Correlation analyses of several motor symptoms and neuropsychological results revealed that there was a significant negative correlation between upper motor neuron symptoms and MMS, as well as memory tests. The evidence for multisystem degeneration in ALS has prompted speculation that more sensitive neuropsychological measurements might reveal cerebral dysfunction in ALS patients who are not presenting evident dementia. PMID- 2265970 TI - Interhemispheric processing in left- and right-handers. AB - Inter- and intrahemispheric processing for left- and right-handers were compared in two experiments. In one, subjects performed a digit-matching task and in the other they decided if two letters were part of a previously presented word. On some trials the matching items were presented initially only to one hemisphere (within-hemisphere trials), and hence the match decision could be reached by a hemisphere in isolation. On other trials, one item of the match pair was presented to each hemisphere (across-hemisphere trials), requiring interhemispheric interaction for the match decision. Patterns of performance on within-as compared to across-hemisphere trials were identical for the two handedness groups in both experiments. Furthermore, individual characteristics of subjects such as their hand posture, sex and family history of left-handedness did not affect the pattern of performance. These results suggest that interhemispheric processing may not differ between right- and left-handers. PMID- 2265971 TI - Neurological implications of aniseikonic tilts and stereoscopic completions through homogeneous visual space. AB - In 1965, it was first reported that BROKEN visual contours complete themselves in textured stereovision across empty or homogeneous space and that they do so strongly following directly the optics of crossed versus uncrossed disparities. The importance was then also noted of this completion effect for any neurophysiological model of stereovision. We now extend these measurements with several additional targets and to an analogous aniseikonic target, and confirm that the completion range has a maximum of about 5 degrees. There is much dependence upon target eccentricity and disparity sign, and some on size. That aniseikonic tilts may also be generated over this same range confirms the fact that global neurointegrative processes are of critical importance in all facets of stereovision, and in texture vision in general. PMID- 2265972 TI - Habenula as a relay in the descending pathway from nucleus accumbens to periaqueductal grey subserving antinociception. AB - This study explored the possibility of a relay at habenula for the descending neural pathway of antinociception. The latency of the escape response elicited by radiant heat on the snout of the rabbit was taken as index of nociception. (1) Microinjection of 20 micrograms of morphine into nucleus accumbens resulted in a one-fold increase in nociceptive threshold 20-40 min after the injection. This effect of morphine was markedly attenuated by naloxone or met-enkephalin antiserum administered to the nucleus habenula, suggesting that the release of met-enkephalin in habenula is essential for the antinociception induced by morphine injected into nucleus accumbens. (2) Injection of 10 micrograms of morphine into habenula produced a significant increase in escape response latency 20-40 min after the injection. This antinociceptive effect of morphine was attenuated by naloxone or muscimol, and enhanced by bicuculline methochloride administered to periaqueductal grey, suggesting that morphine may act on habenula to activate a descending neural pathway extending to periaqueductal grey to induce an antinociceptive effect, which seems to utilize endogenous opioid peptides and gamma-aminobutyric acid as its mediators. Taking together, the results suggest that habenula is an important relay in the descending neural pathway from nucleus accumbens to periaqueductal grey subserving antinociception. PMID- 2265973 TI - Stimulation of 36Cl- influx into rabbit cerebral cortex microsacs by the endogenous antigen S-100. AB - The rate of accumulation of 36Cl- ions into rabbit cerebral cortex microsacs has been studied under various conditions. Such a parameter is increased by 164% by 10(-4) M GABA, the effect being reversed in the presence of 10(-4) M bicuculline and 10(-4) M picrotoxin. Incorporation of the endogenous antigen S-100, by a preincubation of the fraction with the protein in the presence of 2.5 mM Ca++, brings about a 56% stimulation of 36Cl- influx rate. This effect does not seem to be additive with that of GABA. The S-100 effect is reversed by picrotoxin but not by bicuculline. The overall pattern of data suggests an action of the antigen directly at the GABAA receptor complex and in particular at the GABA activated Cl channel. PMID- 2265974 TI - Birth weight and pathogenesis in phenylketonuria. AB - The birthweights of an ethnically homogeneous sample of infants with phenylketonuria, their unaffected siblings, and control infants were compared after adjusting for the effects of: mother's age, mother's date of birth, mother's height and obstetric history, the length of gestation, the infant's sex, the place and date of birth. There were no significant differences between the infants with phenylketonuria and their unaffected siblings either in adjusted or unadjusted birthweights. Control infants had slightly, but statistically significant, greater adjusted and unadjusted birthweights than the combined phenylketonuria and unaffected sibling groups. This effect of the phenylketonuria gene is a previously unreported finding but unlikely to be related to the pathogenesis of phenylketonuria. Our results do not provide support for the "justification" hypothesis that the mental and neurological defects in phenylketonuria result from prenatal tyrosine deprivation which would be reflected in lower birthweights. PMID- 2265975 TI - Testosterone and hand performance in right-handed young adults. AB - The relationship between serum testosterone level and hand performance was studied in right-handed young adults without familial sinistrality. Hand performance was measured by a dot-filling task, which was found to be associated with serum testosterone depending upon sex. In women, the right- and left-hand performance was found to be negatively linearly related to testosterone; there was no significant correlation between the right- minus left-hand performance and testosterone. In men, right- and left-hand performance were found to be directly and inversely related to testosterone, respectively. This pattern exhibited some variations depending on eye and foot preferences. The difference in performance between hands was found to be positively linearly related to serum testosterone levels in men. PMID- 2265976 TI - Testosterone and nonverbal intelligence in right-handed men and women. AB - The relationship between serum testosterone level and nonverbal intelligence was studied in right-handed young adults. Hand preference was assessed by the Edinburgh Handedness Inventory. Serum testosterone level was determined using tritium-marked-radioimmunoassay. Only in men, nonverbal intelligence (Cattell's Culture Fair Intelligence Test) was found to be significantly and directly related to serum testosterone levels. It was concluded that the serum testosterone in young adults is associated with nonverbal intelligence exhibiting fundamental differences between men and women. PMID- 2265977 TI - Relationship of testosterone and nonverbal intelligence to hand preference and hand skill in right-handed young adults. AB - The relationship between serum testosterone level and nonverbal intelligence was studied in right-handed young adults with regard to handedness. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was measured by a peg moving task. Serum testosterone level was determined using tritium-marked radioimmunoassay. Visual-spatial performance (nonverbal intelligence) was measured by Cattell's Culture Fair Intelligence Test. In men with consistent right-hand preference (GSs: 80 to 100), IQ was found to be positively linearly related to serum testosterone, which exhibited two regression lines belonging to low and high difference in skill between hands. In females with consistent right handedness, there was a negative linear correlation between IQ and serum testosterone, which also exhibited two different regression lines according to difference in skill between hands. In males with moderate right-hand preference (GSs 50 to 75), IQ was found to be positively linearly related to serum testosterone, exhibiting two different (same slopes) regression lines according to difference in skill between hands. In females with moderate right-hand preference, IQ first increased and then decreased with serum testosterone, exhibiting a quadratic relationship. These results suggested that serum testosterone in young adults may be associated with visual-spatial performance depending upon sex, hand preference, and hand skill. PMID- 2265978 TI - P 300 latency of the auditory evoked potential in dementia. AB - A two-tone discrimination paradigm was employed to elicit the P 300 component of the event related brain potential from 10 demented patients. P 300 latency was found not to be prolonged in the dementia group compared to age normative predictions derived from a patient control group. This finding contrasts with a number of studies of demented patients that generally found P 300 latency to exceed normative data. It was concluded that the results of normal latency in dementia is obviously due to the control of medication and the exclusion of patients who were unable to perform the required counting task. PMID- 2265979 TI - Early childhood testing and school learning problems: a cross-validation. AB - Educators in the early school grades often find themselves in a dilemma when evaluating children's skills. Formal testing procedures are often inappropriate for young children and can wrongly identify them as deficient. The purpose of this study was to help teachers in making early decisions regarding individual children that would be accurate and helpful in designing educational programs. A screener was identified during the first year that discriminated between kindergarten children identified by their teachers as high-achieving or low achieving. The results of a subsequent cross-validation yielded a relationship between the screener and the teachers' evaluations that was statistically significant. PMID- 2265980 TI - The relationship between ECT nonresponsiveness and calcification of the pineal gland in bipolar patients. AB - It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5 methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients. PMID- 2265981 TI - The relationship of pineal calcification to subtypes of tardive dyskinesia in bipolar patients. AB - Recent studies have suggested that bipolar patients may be at high risk for developing tardive dyskinesia (TD) if exposed to chronic neuroleptic therapy. It has been suggested that reduced melatonin secretion may favor the development of TD in bipolar and schizoaffective patients. Since pinealectomized rats have been reported to develop increased incidence and severity of abnormal chewing movements, and as depression is associated with reduced melatonin secretion, the increased risk of TD in bipolar patients may be associated with diminished melatonin secretion. Evidence suggestive of an inverse correlation between pineal calcification and reduced melatonin secretion, led me to study the relationship between pineal calcification on CT scan and the severity of axial (truncal) and limb and orofacial dyskinesias in bipolar patients with TD. The incidence of pathologically enlarged pineal calcifications (i.e., greater than 1 cm in diameter) in the bipolar patients was 25 times greater than the reported incidence in the literature among nonpsychiatric patients. In addition, there was a significant difference in scores of axial dyskinesias between patients with pineal calcification of less than 1 cm in diameter compared to those with pineal calcification of greater than 1 cm in diameter (F = 3.24; p = .04, one-way ANOVA). There was no significant association between scores of limb and orofacial dyskinesias and pineal calcification. These findings suggest a meaningful association between the presence of enlarged pineal calcification, and axial dyskinesias in bipolar patients. Further studies using direct plasma melatonin measurements are required to more precisely define the association between TD and melatonin secretion in bipolar patients. PMID- 2265982 TI - The relationship between ECT responsiveness and subtypes of tardive dyskinesia in bipolar patients. AB - Despite intensive research, the mechanisms of action of electroconvulsive therapy (ECT) remain elusive. In addition, there are no known biological factors predicting ECT responsiveness in bipolar patients. A study was conducted to investigate the relationship between ECT responsiveness and tardive dyskinesia (TD), a common side effect of neuroleptic therapy, and its subtypes (i.e., orofacial and limb-axial dyskinesias) in a group of 18 bipolar patients. There was a significant difference in orofacial dyskinesia scores between ECT responders and non-responders (p less than 0.005), while there was no significant association in scores of limb-axial dyskinesia between ECT responders and non responders. These findings suggest an association between ECT responsiveness and the presence of orofacial dyskinesias in bipolar patients with TD and add further support to the notion that TD is a heterogeneous disorder comprising at least two subtypes with distinct underlying pathophysiological mechanisms. PMID- 2265983 TI - Balint's syndrome in Alzheimer's disease: visuospatial functions. AB - A subgroup of patients with Alzheimer's disease (AD) developed Balint's syndrome, an uncommon and incompletely understood disorder of visuospatial processing. We characterized the visuospatial features of three AD patients with Balint's syndrome and compared them to three comparably demented AD patients without this syndrome. On visuospatial tasks, the Balint patients were unable to integrate visual stimuli over space. On contrast sensitivity testing, the Balint patients had significantly decreased contrast sensitivities for low spatial frequency gratings (0.5, 1.0 and 2.0 cpd) alternated at 7.5 Hz. Furthermore, the Balint patients had left visual field attentional deficits and normal hemifield P100 visual evoked potentials. In AD, Balint's syndrome involved decreased sensitivity to low spatial frequencies necessary for global visuospatial analysis, a disturbance suggesting damage to the magnocellular visual system in the occipitoparietal association cortex and, possibly, in the optic nerves. PMID- 2265984 TI - The late event related potentials CNV and PINV in normal and dyslexic subjects. AB - The most prominent ERP to occur during intervals of preparation and anticipation is the contingent negative variation (CNV) or expectancy wave. The resolution of this wave is called the postimperative negative variation (PINV). The purpose of this study was to distinguish the characteristics of the CNV and the PINV in a group of children with reading disabilities or dyslexia and to compare them from a group of normal readers. Nine righthanded boys aged between 10-13 years with reading disabilities were studied. The children were matched with a group of nine normal readers. Four derivations were used: frontal, central, parietal and occipital zones, with reference to linked ears. Data were analyzed using multivariate procedures. Significant differences between groups in CNV amplitude and in PINV amplitude and latency at the left parietal site were observed. We discuss the participation of this zone and we consider processes like expectancy, attention and brain activity signal processing in the differences mentioned. PMID- 2265985 TI - Lectin binding in murine tumour lines with different malignant characteristics. Effect of enzyme (pronase, neuraminidase) treatment on lectin labelling. AB - We used 5 syngeneic murine tumour systems for studying quantitative lectin surface binding of intact viable tumour cells. We also investigated, for 3 of the tumours, whether the lectin binding sites were susceptible to proteolytic enzyme (pronase) or neuraminidase treatment. There were significant differences between two of the tumour lines in the binding of wheat germ agglutinin (WGA), concanavalin A (ConA). peanut agglutinin (PNA), soybean agglutinin (SBA) and Ulex europeus agglutinin (UEA). There were also variations in lectin binding between the other tumor lines, but these differences were not statistically significant. Lectin binding showed no evident relationship to the malignancy or the metastasis forming capacity of the respective tumour cell line. Proteolytic treatment, which drastically affects intravenously induced experimental metastasis formation by one of the tumours, caused a decreased binding of SBA, ConA and WGA. Neuraminidase treatment increased both PNA and SBA binding in three different cell lines, presumably by removing sialic acid masking D-galactose and N-acetyl-D galactose-amine groups. PMID- 2265986 TI - Tumor radiocurability: relationship to intrinsic tumor heterogeneity and to the tumor bed effect. AB - Recent in vitro clonogenic assays of cells from human head and neck carcinomas recurring after fractionated irradiation showed that the mean radiation resistance was significantly greater than that of cells from unirradiated head and neck cancers. Analysis of these data using the linear-quadratic formalism of radiation inactivation indicates that such increased resistance was associated with a large decrease in the parameter describing cell killing by one-hit processes, while the parameter describing cell inactivation by two-hit processes was unchanged. These data suggest that head and neck carcinomas contained intrinsically radioresistant tumor subpopulations that were selected for during the fractionated radiation therapy. Consequently, we have generated a model of how the phenomenon of clonal intraneoplastic diversity might be related to the selection of radioresistant sub-populations. There is, however, an additional major modulating factor which may impact upon the proposed selection process, known as the tumor bed effect. This effect refers to the fact that solid tumors grow at slower rates and to decreased carrying capacities in radiation-damaged normal tissue stroma. We hypothesize that the tumor bed effect is a reflection of an altered, hostile microenvironment within which competition among neoplastic subpopulations for limited resources is increased. This then produces a situation leading to extinction of minority subpopulations within heterogeneous neoplasms, regardless of whether such populations are radioresistant. The final result of these selection/extinction processes will be dependent upon total dose, dose per fraction, overall time, and the initial partial volume percentages of radioresistant subpopulations. PMID- 2265988 TI - Control of choroidal blood flow by the nucleus of Edinger-Westphal in pigeons: a laser Doppler study. AB - Anatomical studies in birds have suggested that choroidal blood flow may be regulated by a circuit involving the following serially-connected components: the retina-the suprachiasmatic nucleus (SCN)-the medial subdivision of the nucleus of Edinger-Westphal (mEW)-the ciliary ganglion-the choroidal blood vessels. In order to better clarify the role of this circuit, we examined the effects of electrical stimulation of EW on choroidal blood flow in the ipsilateral eye, using laser Doppler velocimetry to monitor choroidal blood flow in the superior pole of the eye. Baseline choroidal blood flow values (144-311.3 mg/min per eye) were found to be comparable to those previously reported in rabbits, cats and primates. Stimulation of EW dramatically increased choroidal blood flow. The increases were current-related and the average maximal increases ranged between 300-700% above baseline values. In contrast, EW stimulation had little or no effect on overall bodily blood flow. All EW stimulation sites were later verified histologically. These results indicate that the SCN-mEW circuit in birds may be involved in mediating increases in choroidal blood flow, possibly in response to the levels of retinal illumination. Such adaptive neural regulation of choroidal blood flow may play an important role in mitigating the potentially deleterious effects of light on the retina. PMID- 2265987 TI - Correlation between cell surface oligosaccharides and tissue target-selective adhesion of two rat adenocarcinoma cell lines. AB - We observed that two rat colon adenocarcinoma variants originating from a single parental cell line and differing by their progressive and metastatic capacities in syngeneic BDIX rats differed by their organ distribution after intravenous injections. The PROb cells accumulated in the lung, wherefrom the REGb cells were rapidly cleared. In order to explore the role of cell surface glycoconjugates in organ-specific metastasis, cytofluorometric and histochemical studies using labelled lectins were performed. This revealed that the metastatic variant PROb presented more alpha-L-Fuc(1----2) beta D-Gal-R structures than the regressive nonmetastatic variant REGb. At variance, REGb cells exposed more D-galactosyl and N-acetyl-D-galactosaminyl residues than PROb cells. Monosacharides inhibited specifically cell adhesions on frozen organ sections. L-Fuc and N-acetyl-D galactosamine (D-GalNAc) most strongly inhibited the adhesion of PROb cells on lungs, whereas D-Gal and D-GalNAc most strongly inhibited that of REGb cells. On the liver, adhesions of both cell lines were inhibited by D-Gal and D-GalNAc. These observations support the involvement of sugar-lectin receptors in the adhesion of these cells to the lungs or liver. The possible involvement of previously described lectins is discussed. PMID- 2265989 TI - The response of rat vitreal oxygen tension to stepwise increases in inspired percentage oxygen. AB - The effect of graded systemic hyperoxia on vitreal PO2 distribution has been determined for the rat eye. Oxygen tension profiles were measured, using oxygen sensitive microelectrodes, as a function of distance from the internal limiting membrane as the inspired oxygen percentage was increased in 10% steps from 20 100%. Depending on the original touching location of the microelectrode on the retina, there could be substantial PO2 gradients within 500 microns of the retina; at greater distances vitreal PO2 was constant and a function of the inspired oxygen percentage. Whatever the location of the microelectrode in the vitreous, PO2 rose with increasing hyperoxia. The relationship between vitreal PO2 and inspired oxygen was nonlinear with a central relatively flat region between 50-80% inspired oxygen. The ratio between vitreal PO2 during 100% O2 breathing and air breathing was 3.42 +/- 1.08 (standard deviation, n = 7). Possible explanations for the plateau region are the maintenance of a relatively constant PO2 by vascular autoregulation and/or the buffering of capillary PO2 by hemoglobin. The rat eye, therefore, responds to hyperoxia similarly to that of the cat and monkey but differs from that of the miniature pig where there is no rise in preretinal PO2 during hyperoxia. PMID- 2265990 TI - Human retinal pigment epithelium contains two distinct species of superoxide dismutase. AB - Superoxide dismutase (SOD) molecules occur in all cells exposed to an oxygen containing environment, including retinal pigment epithelial (RPE) cells. Previous studies of nonhuman RPE have either probed specifically for copper-zinc containing SOD (CuZn-SOD) or have not distinguished between CuZn-SOD and the SOD molecule that contains manganese (Mn-SOD). The authors used specific enzymatic assays and immunologic probes, both in vivo and in vitro, to show that human RPE cells contain both CuZn-SOD and Mn-SOD. The CuZn-SOD had a diffuse cytosolic distribution, whereas the Mn form was located primarily in the mitochondria. The role of SODs in protecting the chorioretinal complex against oxidative damage and with regard to aging processes is not well understood and warrants further investigation, and the two cellular forms of SOD should be considered in future studies. PMID- 2265991 TI - Selective inhibition of growing pigment epithelial cells by a receptor-directed immunotoxin. AB - An immunotoxin conjugate of a murine monoclonal antibody against human transferrin receptors and the A chain of ricin was examined for its potential to inhibit selectively the growth of retinal pigment epithelial (RPE) cells which grow in an uncontrolled manner in proliferative vitreoretinopathy. The probable efficacy of such an agent in vivo stems from the observation that actively proliferating cells possess many more transferrin receptors than normal quiescent cells. The authors showed in vitro that the immunoconjugate (454A12 MAB-rRA) inhibits protein synthesis in actively dividing RPE cells but has a smaller or no effect on protein synthesis by confluent, nondividing RPE cells. The effect was specific in that neither the free ricin A chain (rRA) nor the monoclonal antibody (454A12 MAB) alone has any inhibitory effect. Furthermore, the antibody competes with the immunotoxin and suppresses the latter's toxicity. This immunotoxin has applications for therapy in conditions in which the pathologic proliferation of RPE cells occurs. PMID- 2265992 TI - High-speed photography of Er: YAG laser ablation in fluid. Implication for laser vitreous surgery. AB - The mechanism of Er:YAG laser-induced long-range damage in intraocular surgery was investigated using high-speed photography. A short pulse of 2.94-microns radiation delivered by an optical fiber into an aqueous medium causes rapid localized heating and vaporization and creates a bubble at the tip of the fiber. The size of the bubble depends on the pulse energy and is about 1 mm at 1 mJ. The shape of the bubble has multiple lobes, which can be attributed to the spiky output of the laser pulse. The expanding bubble can cause thermal and mechanical damage to tissues. In addition, laser spikes propagating through the bubble can strike and damage tissue on the distal side of the bubble. In both mechanisms the damage zone approximates the bubble size and can be greater than 1 mm, ie, 1000 times the steady-state absorption length of water at 2.94 microns. The authors discuss ways to reduce the damage zone by bubble confinement. PMID- 2265993 TI - Intraocular pressure-dependent light sensitivity in glaucoma. AB - The intraocular pressure-dependent light sensitivity of discrete retinal points was measured using the Heijl-Krakau automated light-emitting diode perimeter with an appropriate software program. A total of 300 measurements of light sensitivity were recorded from six retinal points during the test period of 8-10 min; increased intraocular pressure was induced using a Langham scleral suction-cup system. The ocular pulsatile blood flow and the ophthalmic arterial pressure were measured in the same patients. The fluctuation of the light sensitivity was less than 5% over the test period in healthy eyes and remained unaffected by an intraocular-pressure increment of 20 mm Hg; a small decrease of sensitivity occurred at a pressure increment of 30 mm Hg. In glaucomatous eyes the light sensitivity was lower and the fluctuation of the light sensitivity at some but not all retinal points was substantially greater than in the controls. In the glaucomatous eyes, and intraocular-pressure increment of 20 mm Hg increased the fluctuation and decreased the light sensitivity. The pulsatile ocular blood flow was lower in the glaucomatous eyes but not severe enough to be solely responsible for the loss of vision. The coexistence of retinal points with normal and abnormal stabilities of light sensitivity in glaucomatous eyes was consistent with impaired blood flow in the lamina cribrosa. PMID- 2265994 TI - Effect of fluorescein on the electrical potential difference across isolated rabbit corneal endothelium. AB - The authors investigated whether fluorescein sodium affects the in vitro endothelial function of rabbit corneas. As an index of this function, the transendothelial electrical potential difference (TEPD) was used. The TEPD in a balanced salts and glucose (BSG) control solution increased for the first 30 min and then decayed slowly, reaching about 60% of its original value after 5 hr. When a BSG solution containing 5 micrograms/ml of fluorescein sodium was used, the TEPD time course was similar to the control solution. Since this fluorescein sodium concentration is about sevenfold higher than that seen in the anterior chamber of ocular patients, these results reassure users that no toxic effect of fluorescein is discernible at concentrations relevant to ophthalmic practice. With a fluorescein sodium concentration of 500 micrograms/ml, the TEPD decreased below control values after 4 hr of exposure, but such a concentration is approximately 5000-fold higher than that seen in the anterior chamber of patients. The adverse effect of fluorescein on TEPD is probably irrelevant for standard systemic clinical use. PMID- 2265995 TI - Mental health attitudes and practices of Soviet immigrants. AB - A survey of mental health knowledge, attitudes and help-seeking practices was conducted with 415 Soviet immigrants to Israel. The purpose of the study was two fold: to provide data for mental health services and outreach programs designed for this immigrant group and to obtain a "proxy window" into these attitudes and behaviors in the Soviet Union itself. The results show that almost 20% of the immigrants reported consultation to formal agents in Israel and about half of these reported similar consultation in the USSR. An almost equal proportion consulted the family. Univariate and multivariate analysis show that demoralization, marital status, and religiosity were significantly associated with help-seeking. The second part of the survey explored Soviet immigrant attitudes to mental illness and the mentally ill by means of case vignettes and social situations, respectively. The respondents were able to detect abnormal behavior, but did not label it as psychopathology. Their overall tolerance of such behavior was low. These attitudes did not change over time nor seem to be influenced by reported abuses of psychiatry in the USSR. PMID- 2265997 TI - How "mild" is mild Munchausen syndrome by proxy? AB - This paper describes four cases of Munchausen Syndrome by Proxy (MSbP), in each of whom the disorder could be considered mild from the physical viewpoint. However, in all cases a severe emotional disturbance was evident in the mother child relationship, and certain significant features were common to each case, including the dynamics of the development of the disorder. In all, maternal anxiety resulted in the mother perceiving the child as sick, leading to her insistence that he/she receive medical attention. A follow-up over several years showed severe disturbances in the emotional development of all the children. It is thus suggested that mild cases of MSbP may be indicators of severely disturbed mother-child relationships, raising important questions about their proper management. PMID- 2265996 TI - Disease appraisals as a coping strategy with cancer threat. AB - The aim of the present study was to test the hypotheses that minimizing cancer threat is a prevalent and useful coping strategy for breast cancer patients. Forty-nine primary breast cancer patients and a comparison group of 57 healthy women appraised cancer, heart disease and surgery. The hypotheses were confirmed. Breast cancer patients appraised cancer and the two other disease states significantly more optimistically than did healthy respondents. Breast cancer patients appraised the three diseases more optimistically at the beginning of the post-mastectomy year than at its end, and patients with worse prognoses appraised cancer in a more optimistic direction than patients with a more favorable one. More minimization was prospectively related to a better social adjustment. PMID- 2265998 TI - Anniversary reaction as a symptom of grief in traumatized persons. AB - Anniversary reaction is a somatic or mental illness that can occur near a date which is emotionally important to traumatized persons. Usually, the person thus affected makes no association between his illness and the onset of the reaction. A case history is given of a 49-year-old Jewish woman who was hidden in the Netherlands during the German occupation in World War II. Her parents were exterminated in a concentration camp when she was four years old. She never permitted herself the normal process of grief and bereavement until she began psychotherapy. The anniversary reaction she experienced on the Netherland's commemoration day for war victims, more than 40 years after the war, was the beginning of her process of mourning. PMID- 2265999 TI - Collaboration of clergy and psychotherapists in treating psychiatric patients. AB - The following case studies describe the psychotherapeutic treatment given to three guilt-ridden patients, with the aid of rabbis. Collaboration between clergy and mental health professionals in treating such patients is discussed. PMID- 2266000 TI - Endotoxin releases platelet-activating factor from human monocytes in vitro. AB - The role of platelet-activating factor (PAF) in human endotoxaemia was investigated by incubating human monocytes from 27 subjects with S. minnesota endotoxin in vitro. Monocytes synthesized 1.01 +/- 0.4 x 10(-10) M to 5.3 +/- 1.51 x 10(-9) M PAF after 60 min of incubation with endotoxin at concentrations of 1 x 10(-8) M and 4.5 x 10(-6) M respectively. The endotoxin-stimulated release of PAF was not significantly increased in monocytes cultured on a human endothelial cell monolayer. This rapid release of PAF in response to endotoxin is consistent with a role for monocyte-derived PAF as a toxic mediator of the acute systemic changes observed in patients with endotoxin-related septic shock. PMID- 2266001 TI - The polyclonal activation of lymphocytes and T cell mitogenicity by a unique sialic-acid-binding lectin from the hemolymph of Achatina fulica snail. AB - A unique sialic-acid-binding lectin, AchatininH, isolated from the hemolymph of Achatina fulica snail was found to be strongly mitogenic, as monitored by [3H]thymidine incorporation assay, to rat and human lymphocytes. However, the degree of mitogenic response varied with the type of cell population. As indicated, this lectin induced proliferation of purified T lymphocytes and rat thymocytes, whereas it was less mitogenic towards peripheral lymphocytes of pregnant rats and was not mitogenic towards B lymphocytes. Furthermore, the mitogenic response was inhibited by the sialic-acid-containing disaccharide, a strong inhibitor of this lectin. This suggests that lymphocyte cell surface molecules containing sialic acid residues are important for this interaction and may have a structure similar to that of AchatininH receptors. Although this lectin showed strong mitogenicity towards lymphocytes, it showed very weak leucoagglutination. Surprisingly, PHA-induced blastogenesis was inhibited by the same dose of AchatininH as caused mitogenic activity in resting lymphocyte culture. The degree of suppression was higher for the lymphocytes isolated from pregnant rat blood compared to the non-pregnant control. Since the 51Cr-uptake assay and the cell viability test results negate the potential cytotoxic activity of this protein, the immunosuppression induced in the presence of PHA by AchatininH may be the additive effect of two mitogens causing an increased cell density-dependent arrest. AchatininH does not have complement-like activity, but induces potent polyclonal activation of B cells as measured by the reverse hemolytic plaque assay. PMID- 2266002 TI - Cadmium inhibits spontaneous (NK), antibody-mediated (ADCC) and IL-2-stimulated cytotoxic functions of natural killer cells. AB - Cadmium (Cd2+), an environmental contaminant, has been shown to inhibit, even if not totally, natural killer (NK) cell-mediated cytotoxicity and antibody dependent cellular cytotoxicity (ADCC) of human peripheral blood lymphocytes in a dose- and time-dependent manner. The presence of Cd2+ during the early period of the cytotoxic assay was needed to obtain maximal inhibition. Preincubation of either effector or target cells with Cd did not result in any inhibitory effect. Cd2+ also inhibited the cytotoxic activities of effector cells prestimulated with IL-2 for 18 h or 4 days, which mostly consist of NK cells. Our results indicate that Cd2+ did not block effector-target conjugate formation, but rather interfered with the hydrolysis of phosphoinositides, as shown by the decrease of inositol trisphosphate (IP3), which is known to release stored Ca2+. PMID- 2266003 TI - Thymosin alpha 1 and thymosin beta 4 modulate human colonic lamina propria lymphocyte function. AB - Thymosin alpha 1 and thymosin beta 4 are two thymosin fraction 5-derived peptides with the capacity to alter a variety of immune functions in human and animal models. In this study we investigated the effect of both thymosin alpha 1 and thymosin beta 4 on human colonic lamina propria lymphocyte (LPL) proliferation and ornithine decarboxylase (ODC) activity. LPL from eighteen human colon specimens were cultured in the presence or absence of thymosin alpha 1 and thymosin beta 4. We found that both peptides suppressed thymidine incorporation into LPL. However, thymosin alpha 1 and thymosin beta 4 did not alter thymidine incorporation into phorbol ester (PDB) and calcium ionophore (ionomycin) stimulated LPL. Furthermore, thymosin alpha 1 and thymosin beta 4 also did not alter ODC activity in Con A-stimulated LPL. These results suggest that both peptides alter LPL proliferation, and that the mechanism for this inhibition may not involve the calcium fluxes or the ODC pathway but may involve protein kinase C. We postulate that thymosin alpha 1 and thymosin beta 4 may participate in the modulation of the human mucosal immune system. PMID- 2266004 TI - Regulation of interleukin-2 production and phosphatidylserine synthesis in Jurkat T lymphocytes by K+ channel antagonists. AB - Modification of phospholipid metabolism during T cell activation has been repeatedly reported. Recently, we have shown that phytohaemagglutinin, CD3 and CD2 mAbs, which are potent in vitro activators of helper T lymphocytes, markedly inhibit phosphatidylserine synthesis concomitantly as they induce the secretion of IL-2. In this paper, we show evidence that in T lymphocytes K+ channels, which have been shown to participate in the cell activation process, are also reciprocally related to phosphatidylserine synthesis. In fact, in resting T cells the drugs affecting the activity of K+ channels, such as quinine and 4 aminopyridine, induce a rise of phosphatidylserine synthesis. In activated cells, quinine and 4-amidopyridine also caused a rise in phosphatidylserine synthesis which paralleled a decreased production of IL-2, strongly suggesting that these two events are correlated in a reciprocal manner. More precisely, phosphatidylserine synthesis was stimulated by drugs which have been reported to inhibit potassium channels in lymphocytes, e.g. quinine, 4-aminopyridine, tetraethylammonium. These data suggest that the decreased PS synthesis observed during T cell activation intervenes in the cascade of events leading to IL-2 secretion. The decrease in the biosynthesis of this phospholipid seems to be dependent on the activity of K+ channels. PMID- 2266005 TI - Managing hospital-physician relations: a strategy scorecard. AB - Since the initiation of prospective payment, hospitals have been struggling to develop strategies that improve their prospects for long-run viability. Foremost among these strategy formulations have been efforts to build hospital-physician relations. This article reviews several popular strategies designed to achieve mutually satisfying hospital-physician relations. PMID- 2266006 TI - Addiction among nurses: does the health care industry compound the problem? AB - An equation, termed SNAO (Stress, Narcotics and other drugs, Access, and Opportunity), was developed to illustrate certain aspects of the health care environment that are potential contributors to the problem of chemical dependency among nurses. The intention is to provide a useful tool to hospital administrators who are faced with this complex dependency problem. PMID- 2266008 TI - Health care can expect greater financial pressures in the near and long-term future. PMID- 2266007 TI - Quality of care and the patient: new criteria for evaluation. AB - Quality in health care has two critical components: quality in practice and quality in perception. The first involves meeting your own or some other set of standards; the second, meeting your customers' expectations. Neither of these essentials will, by itself, carry a hospital far. This article examines the extent to which customer perception is important in understanding the concept of quality in health care. PMID- 2266009 TI - Relationship between commitment to hospital goals and job satisfaction: a case study of a nursing department. AB - Why is it that people in the same occupation doing similar work in the same department experience different levels of intrinsic satisfaction? This article sheds light on this question and provides hospital administrators with guidelines for improving employee motivation through intrinsic job satisfaction. PMID- 2266010 TI - Hospital cost accounting: who's doing what and why. AB - The movement away from cost-based reimbursement by Medicare and other third party payers has prompted an increasing number of hospitals to implement more advanced costing techniques in their operations. Findings from a recent survey of hospital executives regarding cost accounting methods shed light on the extent of this trend. PMID- 2266011 TI - HCMR interview: Dennis R. Barry. Interview by Montague Brown. PMID- 2266012 TI - Vertical integration in health services: theory and managerial implications. AB - A vertically integrated health care system is an arrangement whereby a health care organization offers, either directly or through others, a broad range of patient care and support services. This article discusses the market forces and strategic considerations driving the recent trend toward vertical linkages in health care markets and examines some of the managerial implications and issues associated with this vertical restructuring trend. PMID- 2266013 TI - Facing up to racism in the NHS. PMID- 2266014 TI - Uncertainty overshadows pay round. PMID- 2266015 TI - NVQs. Support staff dilemma. PMID- 2266016 TI - Training. Violence to staff: a neglected danger. PMID- 2266017 TI - Resource management. All hands to the sails. PMID- 2266018 TI - Gripe water: what is it? Why is it given? AB - Large numbers of babies are given gripe water for no valid reason or for only trivial symptoms, write Cynthia Illingworth and John Timmins. When a health visitor survey of Sheffield mothers and babies showed how widespread was the practice of giving gripe water, they decided to seek information about the nature of gripe water, the conditions which it is supposed to treat and its use by a representative number of women. PMID- 2266019 TI - Public health. Surma: a cause for concern. AB - Andrew Smart and Nishi Madan describe a campaign in Derby to reduce the use within Asian communities of 'surma', a lead-based eye cosmetic, and to raise awareness among health professionals of the potential hazard this practice presents. A health visitor may bring special insight to questions about traditions and customs pertaining to her client community and about which little may be known by those who do not have a close working relationship with those communities. PMID- 2266020 TI - Working in a prison visitors' centre. PMID- 2266021 TI - Community pharmacists and health visitors. AB - An extended role for pharmacists in primary health care is currently being pursued by the pharmacy profession. An independent enquiry into pharmacy concluded that pharmacists were an underused resource and recommended a wide ranging development of their role. The recommendations of this inquiry were endorsed by the government in its 1987 primary health care white paper Promoting better health. PMID- 2266022 TI - An allergy to wheat: case history of a sufferer. PMID- 2266023 TI - Pertussis immunisation: professional attitudes and knowledge. AB - A survey in Fife found that 98 per cent of health professionals were committed to the prevention of whooping cough. Ninety seven per cent considered pertussis vaccine to be relatively safe and 98 per cent found the current immunisation guidelines satisfactory. However the survey also identified considerable misinterpretation of vaccine contra-indications which would result in many eligible children not being immunised. PMID- 2266024 TI - Counselling attitudes in health visiting students. AB - All health visitors have a counselling function as part of their jobs. When visiting people in their homes they are frequently asked to discuss personal problems and emotional difficulties. It would be helpful if all health visitors developed specific counselling skills say Philip Burnard and Paul Morrison who here describe the results of a piece of research into counselling skills among a group of health visiting students. PMID- 2266025 TI - A school nurse and health visitor working together as health educators. AB - Anne Patterson describes how a request for health information from mothers of children at the local nursery school led to a regular discussion group and a successful partnership between the school nurse and her health visitor colleague. PMID- 2266026 TI - Race and benefits. 2. PMID- 2266027 TI - Whither Nicaragua? PMID- 2266028 TI - US osteopathic medical school finances. PMID- 2266029 TI - Osteopathic postdoctoral education. AB - Osteopathic postdoctoral education is still in transition. With a projected modest decline in the number of graduates and continued increase in the number of intern positions, the profession can now accommodate all graduates in osteopathic internships. Changes have been made in the intern program curriculum and in procedures for approval of residency training to be more responsive to the current healthcare environment and needs of osteopathic graduates. The AOA Department of Education will continue to monitor and report on the impact of these changes. PMID- 2266030 TI - AOA continuing medical education. PMID- 2266031 TI - Research programs of the AOA and their role in osteopathic education. PMID- 2266032 TI - At least 10 million children will be infected with the human immunodeficiency virus (HIV) by the end of this century. PMID- 2266033 TI - History of osteopathic medical education accreditation. AOA Editorial Department. PMID- 2266034 TI - Undergraduate osteopathic medical education. PMID- 2266035 TI - Effect of disease prevalence on a test's predictive value. PMID- 2266036 TI - Error in response to letter on veal calf production. PMID- 2266037 TI - Veterinary units help military dogs survive scorching Saudi desert. PMID- 2266039 TI - AIDS patients can acquire some infections from animals. PMID- 2266038 TI - Military veterinarians key public health role in Operation Desert Shield. PMID- 2266040 TI - Canine elbow arthrosis registries encouraged. PMID- 2266041 TI - What does organic mean? PMID- 2266042 TI - Humane euthanasia and companion animal death: caring for the animal, the client, and the veterinarian. PMID- 2266043 TI - Memory loss: fact vs fiction. PMID- 2266044 TI - Considerations for use of descriptive epidemiology to investigate fetal loss in dairy cows. AB - Various descriptive approaches were taken in a prospective investigation to characterize fetal loss in cows on a California dairy. The methods and observations were offered for consideration by practitioners engaged in dairy herd health medicine. For 4,732 pregnancies followed from 2,163 cows in a 6.5 year period, the respective proportions (percentage) of cows aborting (1- cumulative proportion not aborting by 260 days) and abortion densities (abortions per 10,000 cow-days-at-risk) were 10.63 and 6.29 for all fetal deaths, 9.36 and 5.49 for deaths resulting in fetal expulsion, and 1.39 and 0.80 for deaths resulting in mummification. The greatest risk of fetal death (119 deaths/10,000 fetuses/d) was observed between 98 and 105 days of gestation, and median age at fetal death ranged from 99.0 to 105.5 days. Abortion density for fetal deaths resulting in mummification for cows conceiving during September (1.61/10,000 fetuses/d) and October (1.63/10,000 fetuses/d) was tenfold greater than that for cows conceiving in February (0.16/10,000 fetuses/d) and was twice that of the overall rate (0.84/10,000 fetuses/d). For cohorts of nonculled cows, abortion rate increased after 5 years of age, after 5 pregnancies, or after 4 calvings. For cows with at least one previous abortion, the proportion aborting (14.50%) was higher than that for cows without a previous abortion (12.14%). For a given gravidity, abortion rate was higher among cows that had experienced a previous abortion, compared with those that had not. These methods and observations may help provide a logical foundation on which to base clinical hypotheses regarding causes of abortion, and they may offer insight into pitfalls of bias and confounding to be anticipated. PMID- 2266045 TI - Biomedical Sciences Corps: a new look at the veterinarian's role in the Air Force. PMID- 2266046 TI - Financial analysis of pseudorabies control and eradication in swine. AB - Computerized decision-tree analysis and simulation modeling were used to evaluate control and eradication strategies for pseudorabies virus (PRV) in swine. Three alternative actions were considered for a hypothetical 100-sow, farrow-to-finish operation: (1) depopulation-repopulation, (2) test-and-removal of seropositives (T&R), and (3) vaccination (of the entire herd or of sows only). The expected monetary values for the vaccination and T&R alternatives were similar, which was consistent with the long-standing controversy over the best strategy for dealing with PRV. When the prevalence rate of PRV was less than or equal to 57%, T&R was found to be optimal; otherwise, vaccination of sows only was recommended. Sensitivity analysis was performed to determine how modifications in some of the original assumptions affected the expected monetary values of each strategy. When higher gross margins for the producer were assumed, T&R was preferred at all prevalence rates. Vaccination was preferred when lower gross margins, lower vaccination costs, or better protective effect of PRV vaccines on reproductive performance were assumed. The use of gene-deleted vaccines in conjunction with the T&R strategy was also evaluated. When this option was available, T&R was favored at any prevalence rate (T&R alone when the prevalence was less than or equal to 20%, or combined with gene-deleted vaccination at prevalences greater than 20%). Depopulation-repopulation was not the best option under any circumstance. Once formulated, a decision-tree analysis can be adapted to the prevailing economic or epidemiologic conditions; hence, it is a useful tool in the PRV decision-making process. PMID- 2266047 TI - Flowers in the blood: opium and veterinary medicine. PMID- 2266048 TI - Serosurvey of horses with evidence of equine monocytic ehrlichiosis. AB - In August 1986, an extensive serosurvey for prevalence of IgG and IgM antibodies against Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (EME), was performed at 2 Ohio racetracks, River Downs (RD) and Beulah Park (BP). Of 840 horses at RD and 574 at BP, 13 and 20%, respectively, were IgG antibody positive (by indirect fluorescent antibody test results), with antibody titer ranging from 1:20 to 1:10,240. The titer observed at highest frequency at both racetracks was 1:80. A higher proportion of horses was ill at RD (operating during the summer months) than at BP (winter track). Of ill horses, 41% (24/58) at RD and 58% (11/19) at BP were seropositive. At RD, 70% (589/840) of all horses and 95% (102/107) of IgG seropositive horses had been stabled only at RD during the month prior to testing. Analysis of these sera by use of an ELISA to detect IgM antibody against E risticii antigen indicated that at RD, 42% (57/137) of the seropositive horses were IgM seropositive. At BP, 17% (20/120) of seropositive horses were IgM seropositive. The larger number of IgM seropositive horses at RD indicates that more horses were recently infected at RD than at BP (P = 0.0001). Therefore, at least half the seropositive horses at RD seemed to have acquired the infection at RD. These serosurvey data also indicate that at BP and RD, 78% (85/109) and 91% (111/122) of IgG seropositive horses, respectively, had subclinical infection. At less than or equal to 1:40 titer, there was no difference in seropositive rates between healthy and ill horses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266049 TI - Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs. AB - Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD. PMID- 2266050 TI - Heinz body hemolytic anemia associated with high plasma zinc concentration in a dog. AB - Acute zinc toxicosis from the ingestion of pennies was diagnosed in a dog with Heinz body hemolytic anemia (PCV = 14%), leukocytosis (51,000 cells/ml) with a left shift (3,060 band neutrophils; 37,740 segmented neutrophils) and monocytosis (4,080 cells/ml), azotemia (BUN = 60 mg/dl), bilirubinemia (total bilirubin = 5.3 mg/dl), hypokalemia (3.0 mEq/L), high serum alkaline phosphatase activity (691 U/L), high total plasma solids (8.1 g/dl), hemoglobinuria, and proteinuria. Despite aggressive medical treatment, renal failure ensued, and the dog died of cardiac arrest. The clinical signs, clinical course, and laboratory findings in this dog were similar to what has been reported in other cases of acute zinc toxicosis in dogs, with the exception of a history of generalized seizures and the findings of Heinz bodies. Although a causative relationship between plasma zinc values and Heinz body formation cannot be proven, their association suggests that oxidative damage to erythrocyte hemoglobin and cell membrane proteins may be involved in the pathogenesis of zinc-induced hemolysis. PMID- 2266051 TI - Metaproterenol intoxication in a dog. AB - Intoxication with metaproterenol, a mainly beta-2 selective agonist, was diagnosed in a dog with tachycardia, tachypnea, weakness, vomiting, and a history of exposure to the drug. Electrocardiography and echocardiography disclosed sinus tachycardia with episodes of ventricular tachycardia and exuberant systolic ventricular function, respectively. Administration of the beta blocking drugs propranolol and atenolol led to resolution of the clinical signs. Excessive sympathetic stimulation caused by metaproterenol is an unusual intoxication in dogs. PMID- 2266052 TI - Combined chylothorax, chylopericardium, and cranial vena cava syndrome in a dog with thymoma. AB - A dog was examined because of anorexia and development of submandibular, sternal, and forelimb edema. Physical examination revealed engorged jugular veins and engorged blood vessels of the conjunctivae and nictitating membranes. Thoracic radiography revealed pleural and pericardial effusions, later identified as chyle. Contrast angiography revealed an intravascular mass, later identified as thymoma, in the cranial vena cava. PMID- 2266053 TI - Megaesophagus attributable to lead toxicosis in a cat. AB - Megaesophagus attributable to lead toxicosis was diagnosed in a 3-year-old spayed domestic shorthair cat. The cat regurgitated when it was distressed by handling, and there was clinical evidence of laryngeal and pharyngeal dysfunction. The cat had macrocytic regenerative anemia, but did not have normoblastosis or basophilic stippling of RBC. The megaesophagus, pharyngeal/laryngeal dysfunction, and anemia resolved with calcium EDTA treatment. PMID- 2266054 TI - Suspected actinobacillosis manifested by facial enlargement in a heifer. AB - Actinobacillosis was the suspected cause of severe, bilateral facial enlargement of 8 months' duration in a 2.5-year-old Holstein heifer. Serum protein electrophoresis revealed a polyclonal gammopathy. Necropsy findings indicated that facial swelling was caused by fibrosis between the skin and underlying bone. Lesions were characterized microscopically by scattered pyogranulomas containing eosinophilic, club-like colonies surrounding gram-negative bacterial rods. The lesion was compatible with diagnosis of actinobacillosis. It is unusual for severe bilateral facial enlargement to be associated with actinobacillosis. PMID- 2266055 TI - Erysipelothrix rhusiopathiae-induced septic arthritis in a calf. AB - A 14-week-old Holstein heifer with a 48-hour history of left tarsocrural joint effusion was referred for evaluation when lameness developed 24 hours after needle aspiration was attempted at the farm. Results of synovial fluid analysis were compatible with diagnosis of septic arthritis, and bacteriologic culture of the fluid yielded Erysipelothrix rhusiopathiae. The calf responded to tarsocrural joint lavage and penicillin G administration. PMID- 2266056 TI - Bilateral arytenoid cartilage paralysis after inhalation anesthesia in a horse. AB - An 8-year-old Quarter Horse gelding was anesthetized for surgical exploration and debridement of a chronic draining wound in the intermandibular space. Anesthesia was without complication other than persistently low PaO2. Severe airway obstruction was evident immediately after extubation, requiring tracheostomy. Endoscopic diagnosis was bilateral arytenoid paralysis, which gradually resolved over the next 7 days. Compression, trauma, or tension of the recurrent laryngeal nerves are the postulated causes of idiopathic laryngeal hemiplegia in horses. The extremely extended position of the head and neck during anesthesia, perhaps compounded by low arterial oxygen content, may have resulted in a hypoxemic insult to the recurrent laryngeal nerves and caused bilateral arytenoid paralysis in this horse. PMID- 2266057 TI - Electroejaculation and artificial insemination in Vietnamese potbellied miniature pigs. AB - A 15-month-old Vietnamese miniature boar was examined because of suspected infertility. A breeding soundness examination was conducted, using electroejaculation under anesthesia for semen collection. Semen values were normal despite a subpubic location of the testes. Artificial insemination of a gilt with extended semen resulted in the birth of a litter 111 days later. Vietnamese potbellied boars have small and sometimes nearly undetectable scrotal pouches, which may cause the producer to question the fertility of the boars. PMID- 2266058 TI - Pulmonary thromboembolism in dogs: 47 cases (1986-1987). AB - Medical records of 47 dogs with pulmonary thromboembolism were reviewed. Middle aged to older dogs predominated and dyspnea and arterial hypoxemia were consistent clinical findings. Thoracic radiographic findings were variable. Cardiac disease, neoplasia, hyperadrenocorticism, disseminated intravascular coagulation, and sepsis were identified most frequently. Multiple disease processes were identified in 64% of the dogs. PMID- 2266059 TI - Cecocolic intussusception in horses: 11 cases (1979-1989). AB - Over a 10-year period, cecocolic intussusception was diagnosed in 11 of 842 horses undergoing surgical treatment for colic at the New York State College of Veterinary Medicine. Eight horses died or were euthanatized because of poor prognosis determined at surgery or because of postoperative complications. Three horses recovered without complication after manual reduction of the intussusception and partial typhlectomy, using an intestinal stapling device. PMID- 2266060 TI - Implications of genetic markers and maps for veterinary medicine. PMID- 2266061 TI - Employment, starting salaries, and educational indebtedness of 1990 graduates of US veterinary medical colleges. PMID- 2266062 TI - What is your diagnosis? Large, centrally located craniodorsal mediastinal mass, with ventral displacement of the trachea and esophagus. PMID- 2266064 TI - Asthma and pregnancy. PMID- 2266063 TI - Interviewer predictions of applicant qualifications and interviewer validity: aggregate and individual analyses. AB - The relative effects of varied interviewee cues on line managers' hiring decisions were examined, as was the relative predictability of various criteria by line managers' interview impressions. Aggregate and individual regression analyses revealed that 3 nursing directors' impressions of 186 nursing applicants shaped their hiring recommendations more than did the applicants' resume credentials. Moreover, managers' interview impressions significantly predicted employees' job attitudes, though predictions of attitudes did not exceed predictions of performance. Finally, individual managers based hiring decisions on different interview impressions, and these impressions forecast employees' job attitudes with differential validity. Implications for future interviewing research are discussed. PMID- 2266065 TI - Asthma during pregnancy. AB - Ineffectively controlled asthma during gestation must be avoided to protect the fetus from untoward effects of maternal hypoxemia and hypocarbia. With current therapy and a compliant gravida, the outcome of pregnancy can be similar to the general population. Physician confidence in antiasthma medications is important. Respiratory distress has pregnancy implications by 20-24 weeks gestation and it is important to have fetal assessment documented when the gravida is treated in the emergency room or during hospitalization for status asthmaticus. PMID- 2266066 TI - Plasma prostaglandin levels from bronchial asthmatic patients assayed by 9 anthryldiazomethane-HPLC method. AB - Plasma prostaglandin (PG) and thromboxane (Tx) levels from bronchial asthmatic patients were assayed by 9-anthryldiazomethane reversed-phase high-performance liquid chromatography method. TxB2 levels from stable bronchial asthmatic patients were significantly higher than those from normal healthy subjects. PGF2 alpha levels were significantly elevated in atopic patients compared with nonatopic ones. PG patterns differed between asthmatic and nonasthmatic conditions in the same patients. PGF2 alpha levels were significantly elevated in the patients with spontaneous attacks compared with those without attacks and 6 keto PGF1 alpha levels were significantly lower in bronchial asthmatic patients having attacks than in the patients without attacks. There were no significant differences of PG levels between mild and moderate asthmatic subjects. Aminophylline injection in patients with mild spontaneous attacks had no significant effects on PG levels which were compared before and after injection. PMID- 2266067 TI - Self-management programs for childhood asthma developed and instituted at the Nishinara-Byoin National Sanatorium in Japan. PMID- 2266068 TI - Environmental control of asthma self-management. AB - We describe a model of asthma self-management based on environmental control of behavior. The model emphasizes aspects of the environment that either prompt or strengthen asthma self-management behavior. In prompting behavior, environmental events function as behavioral cues; in strengthening behavior, they represent reinforcers. We describe concepts related to cueing and reinforcement, and how these operations might be incorporated in individualized self-management programs. Finally, we discuss evidence supporting asthma self-management programs based on environmental control behavior. PMID- 2266069 TI - Asthma education: the perceptions of family physicians. AB - Education and training are important for people with asthma and for their family doctors in order to reduce the morbidity and mortality associated with the disease, but the most appropriate educational strategies have not been clarified. This study was conducted as a needs-assessment survey to examine the perceptions of 193 family physicians in Sydney (Australia) regarding various aspects of asthma management and patient education. Part of this sample of physicians were subsequently involved in a communitywide asthma education program. Although the measurement of airway function by doctors and patients is the cornerstone of the national asthma strategy in Australia, only 43% of family physicians surveyed regularly measured airway function in their offices and most considered that their patients rarely used a peak flow meter. Most physicians agreed with statements suggesting that asthma education was useful but some felt that education could be dangerous, or might result in fewer consultations by asthma patients. These results have provided clear directions for educating family physicians about optimal asthma management. They also provide some insight into potential barriers to the successful implementation of asthma education programs. PMID- 2266070 TI - A portable system for the spectral analysis of cough sounds in asthma. AB - A practical and portable method is described to analyze the sound spectra of coughs. The system is based upon a personal computer and simultaneously collects the sounds of cough heard both at the mouth and through the chest wall together with the airflow at the mouth produced during the cough. Subsequent analysis produce spectrographs of the cough sound linked to the corresponding airflow. The system will be used initially to examine the effects of exercise on the sound of cough in asthma. Further study of cough spectra in this way may be useful in the management of asthma either diagnostically or in the assessment of therapeutic interventions. PMID- 2266071 TI - The use of adrenal substance in the treatment of asthma. 1900. PMID- 2266072 TI - Traumatic heart disease. PMID- 2266073 TI - Traumatic heart disease. AB - Five cases of traumatic heart disease (THD) who sustained blunt chest injury in road accidents are reported. In addition to fracture of the ribs (observed in all the cases), there was fracture of the sternum and rupture of the liver and spleen in one case each. Two patients had flail chest. One presented with recurrent ventricular tachycardia lasting for 72 hours followed by changes suggestive of subendocardial infarction. The second case also had changes like subendocardial infarction and it was preceded by junctional tachycardia with aberrant conduction during the first 48 hours. Ventricular premature beats (VPB) were the only abnormality noted in one case and the remaining two had ST-T wave changes suggestive of inferolateral ischaemia without any arrhythmias. The patient with VPB developed pericardial rub without effusion. There was one death and postmortem revealed ruptured liver and spleen in addition to laceration of the right ventricle and haemopericardium. The electrocardiographic changes persisted for two to eight weeks. All four cases were symptom-free at 12 weeks and treadmill exercise test done after 12 to 18 weeks was normal. PMID- 2266074 TI - Biguanide-induced lactic acidosis. AB - Phenformin-induced lactic acidosis has been thought to be rare in India due to a high carbohydrate intake, use of suboptimal doses of phenformin and a lesser prevalence of alcoholism, as compared to Western countries. We studied the blood lactate levels of 31 non-insulin dependent diabetics (Group A) before and after treatment with phenformin, 75 mg/day for 4 weeks. Blood lactate rose significantly after treatment (mean +/- SEM 16.6 +/- 1.2 mg/dl to 30.7 +/- 2.2; p less than 0.01). Seven patients from this group had blood lactic acid level greater than 72 mg/dl. Six of these patients were restudied off treatment and after 4 weeks of phenformin therapy. The arterial blood pH, pCO2, pO2 and bicarbonate remained unchanged on treatment although a significant rise in blood lactic acid was reconfirmed in these 6 patients. Another group of 12 patients on phenformin for more than six months had significantly lower blood lactate levels as compared to group A (mean +/- SEM 20.2 +/- 1.8 mg/dl vs 30.7 +/- 2.2 mg/dl; p less than 0.01) indicating the possibility of a process of adaptation on prolonged treatment. This possibility was confirmed by a serial follow-up study of 11 patients for a 6 month period on phenformin therapy. A case of biguanide induced lactic acidosis diagnosed and treated by us is described. PMID- 2266075 TI - Follow up of alterations in thyroid hormones and thyrotropin in patients of Hodgkin's disease given mantle radiation. AB - Thirty five patients with Hodgkin's disease who had received mantle radiotherapy to the neck were investigated for thyroid dysfunction serially over many years post radiation. No incidence of clinical hypothyroidism was noted; however, biochemical hypothyroidism (raised TSH, normal T3 and T4) was seen at some time during follow up in 22 patients. Thirteen had high TSH values at the first post radiation examination: in 6 they remained high during follow up and in seven they fell to normal or near normal without thyroxine substitution at any time. TSH abnormalities were seen by 2-3 years post radiotherapy and the return to normal, when it occurred, was seen by 4-6 years. It is advisable to follow up patients with abnormal TSH values following mantle radiation for a further 2-3 years and begin thyroxine substitution only if TSH abnormalities persist. PMID- 2266076 TI - Pharmacokinetics of valproic acid after administration of three oral formulations in healthy adults. AB - The pharmacokinetics and bioavailability of valproic acid was compared in six healthy volunteers after single dose oral administration of 400 mg of the drug in tablet, capsule and syrup form in a crossover manner. Blood samples were collected for 48 hours and valproic acid concentration analysed by enzymatic immunoassay. Following the administration of the three dosage forms, the absorption varied (Ka = Syrup K 2.64 +/- 0.5; tablet 1.57 +/- 0.22; and capsule 0.55 +/- 0.55 h-1). Valproic acid concentration reached a peak level of 102.3 micrograms.ml at 1.9 h after syrup administration, 73 micrograms/ml at 3.3 h after tablet and 44.8 micrograms/ml at 5.4 h after capsule. The bioavailability of tablet and syrup formulation was not significantly different from each other but it differed from capsule form in that the bioavailability was only 52%. PMID- 2266077 TI - Short term anti-tubercular drug therapy and hepatic microsomal enzyme activity. Antipyrine metabolism as an index. AB - The effect of short course chemotherapy on the drug metabolising capacity of the liver was studied in 7 newly diagnosed pulmonary tuberculosis patients, using antipyrine as a model drug. Antipyrine elimination half-life and plasma clearance rate were not significantly altered by 3 weeks of therapy. It is concluded that short course chemotherapy does not affect antipyrine metabolising enzyme activity. PMID- 2266079 TI - Post heparin lipoprotein lipase activity in patients of ischaemic heart disease and in controls. AB - A single high fat meal diet (66 gm fat) was given to 30 healthy males and 20 male patients of ischaemic heart disease (IHD). Ten minutes prior to the 4th postprandial hour, 500 units of heparin--a lipoprotein lipase (LPL) activator- was given, and its effect seen on serum triglyceride (STG) levels observed. Besides higher fasting STG levels, the decline in 4 hour post-prandial STG level was significantly lower in patients of IHD. One explanation for higher fasting STG values and prolonged postprandial lipaemia in these subjects could be deficient LPL activity. PMID- 2266078 TI - Chronic bronchitis: IgA and C3 in acute exacerbations. AB - Serum IgA, secretory IgA and serum C3 were estimated in 22 patients of chronic bronchitis with acute exacerbation. These were compared with 22 normal controls. There was no significant difference in the parameters studied. However, all patients showed a significant change in the above parameters when divided into mild, moderate and severe categories depending on the chronicity of the disease. An inverse relationship between serum C3 and secretory IgA was observed. PMID- 2266080 TI - Effects of commonly used non steroidal anti-inflammatory drugs on gastric mucosa. A clinical, endoscopic and histopathological study. AB - Non steroidal anti-inflammatory drugs (NSAIDS) are known to produce gastro intestinal lesions. In the present work we found that aspirin, indomethacin and oxyphenbutazone caused gastric mucosal damage in 90.9%, 100% and 100% respectively, while ibuprofen and paracetamol caused damage in 33.3% and 37.5% of cases respectively. Thus the latter two drugs were much safer NSAIDs. Furthermore we demonstrated that endoscopic monitoring of patients on NSAIDs is a sensitive method for early detection of gastric mucosal damage. This monitoring may be particularly valuable in high risk subjects on NSAIDs. PMID- 2266081 TI - Percutaneous balloon valvotomy for aortic valve stenosis using single or double balloon technique. AB - Percutaneous balloon valvotomy was performed in 21 cases (aged 6 to 62 years) with moderate to severe aortic valve stenosis, using either single (16 cases) or double balloon (5 cases) technique. All patients had basal transaortic pressure gradient 50 mmHG or above. A majority of patients had significant haemodynamic improvement immediately following balloon dilatation. The mean systolic transaortic pressure gradient reduced from 94 mmHg (range 50 to 160) to 42 mmHg (range 14 to 82; P less than 0.05) immediately after the dilatation. The final gradient was less than 40 mmHg in 11 cases. The mean cardiac index improved from 3.86 L/min/M2 (range 2.8 to 5.2) to 4.14 L/min/M2 (range 3.4 to 5.6; P:NS) following the procedure. There was no death or major complication related to the intervention. There was a procedure-related mild aortic regurgitation in 4 cases. We conclude that percutaneous balloon dilatation is an effective, safe, low cost, nonsurgical method for treating patients with aortic valve stenosis. PMID- 2266082 TI - Role of kallikrein-kinin system in regulation of renal and circulatory function. Physiology and pathophysiology (1). PMID- 2266083 TI - Non surgical management of gallstones. PMID- 2266084 TI - Left atrial myxoma. PMID- 2266085 TI - Thyrotoxic hypokalaemic paralysis. PMID- 2266086 TI - Gastric adenocarcinoma following nodal non Hodgkin's lymphoma. AB - A patient with nodal non Hodgkin's lymphoma who developed a second primary (adenocarcinoma) in the stomach eight months after remission is reported. Implications of a new cancer in non Hodgkin's lymphoma are discussed. PMID- 2266087 TI - Sarcoidosis masquerading as leprosy, pulmonary tuberculosis and urolithiasis. AB - A middle aged man presented as a recalcitrant case of borderline leprosy with concomitant pulmonary tuberculosis and urolithiasis which continued to progress relentlessly despite adequate multiduring antileprosy and antitubercular treatment. After detailed and relevant workup, the diagnosis of sarcoidosis was made. Rapid clinical improvement occurred with steroid therapy. PMID- 2266088 TI - Paramedian diencephalic syndrome. Report of 3 cases. AB - We report three patients who lapsed into coma and subsequently manifested hypersomnolence, amnesia and vertical gaze paresis. Computed tomography revealed bilateral paramedian thalamic infarcts. This clinical symptomatology comprises the paramedian diencephalic syndrome. PMID- 2266089 TI - Hemiplegia as a manifestation of acute mountain sickness. AB - A young mountaineer who developed right sided hemiplegia with aphasia at high altitude is reported. This is an uncommon nervous system manifestation in acute mountain sickness. PMID- 2266090 TI - Transient diabetes following chicken pox. AB - The paper describes two individuals presenting with acute insulin dependent diabetes mellitus for a brief and transient period. Both had had chicken pox infection in the immediate past. After establishing good diabetic control, insulin was withdrawn over a few weeks. Follow-up for the next two years did not reveal recurrence of diabetes. A causal relation between varicella zoster virus and the onset of diabetes is suggested. PMID- 2266091 TI - Nonagglutinable Vibrio cholerae septicaemia. PMID- 2266092 TI - Muscle enzymes-A possible marker for prediction of neuromuscular toxicity in OPC poisoning. PMID- 2266093 TI - Renal transplantation-which donor? PMID- 2266094 TI - Smoking in women: is it really a privilege? PMID- 2266095 TI - Acute myocardial infarction: why delayed arrival in hospital. PMID- 2266096 TI - Effect of levamisole on immune status in patients of recurrent aphthous stomatitis. PMID- 2266097 TI - Viral hepatitis and blood groups. PMID- 2266098 TI - Acute hypotensive reaction to cotrimoxazole. PMID- 2266099 TI - Encephalopathy in shigellosis. PMID- 2266100 TI - Asthma and hyperthyroidism. PMID- 2266101 TI - Nifedipine induced hyperglycaemia. PMID- 2266102 TI - Needle necropsy. PMID- 2266103 TI - Acute pericarditis in aluminium phosphide poisoning. PMID- 2266104 TI - Phenytoin induced osteomalacia and fracture in a young epileptic. PMID- 2266105 TI - Hypokalemic myopathy complicating acute gastroenteritis. PMID- 2266106 TI - Duration of therapy in rheumatic fever without carditis. PMID- 2266107 TI - Protein structure determination in solution by NMR spectroscopy. AB - The introduction of nuclear magnetic resonance (NMR) spectroscopy as a second method for protein structure determination at atomic resolution, in addition to x ray diffraction in single crystals, has already led to a significant increase in the number of known protein structures. The NMR method provides data that are in many ways complementary to those obtained from x-ray crystallography and thus promises to widen our view of protein molecules, giving a clearer insight into the relation between structure and function. PMID- 2266108 TI - Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. AB - The recently-described p59 protein has been shown to be associated with untransformed steroid receptors present in rabbit uterus and rat liver cytosols (Tai, P. K., Maeda, Y., Nakao, K., Wakim, N. G., Duhring, J. L., and Faber, L. E. (1986) Biochemistry 25, 5269-5275; Renoir, J.-M., Radanyi, C., Faber, L. E., and Baulieu, E.-E. (1990) J. Biol. Chem. 265, 10740-10745), while a smaller version of this protein (p56) interacts with glucocorticoid receptors in human IM-9 cell cytosols (Sanchez, E. R., Faber, L. E., Henzel, W. J., and Pratt, W. B. (1990) Biochemistry 29, 5145-5152). In addition to interacting with glucocorticoid receptors, the p56 protein of IM-9 cell cytosol is also found as part of a large heteromeric complex that contains both the 70-kDa and 90-kDa heat shock proteins (hsp70 and hsp90, respectively). Given this association of p56 with the two major stress proteins, I have speculated that p56 may itself be a heat shock protein. In this paper, the effect of heat stress on the rate of synthesis of p56 is determined. Intact IM-9 cells were exposed to 37 or 43 degrees C for 4 h, followed by pulse-labeling with [35S]methionine. Analysis of whole cytosolic extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal an increased rate of radiolabeling for hsp70, hsp90, hsp100, ad hsp110, but no heat-inducible protein of smaller relative molecular mass is detected. However, immune-purification of p56 from normal and heat stressed cytosols with the EC1 monoclonal antibody results in the presence of a 56-kDa protein that exhibits an increased rate of synthesis in response to heat stress. The results of two-dimensional gel Western blots employing the EC1 antibody demonstrate that this heat-inducible protein is indeed the EC1-reactive p56 protein and that the induction effect is not due to unequal yields of p56 during immune-purification. Heat stress has no effect on the composition of the p56.hsp.70.hsp90 complex, except that the complex derived from heat shocked-cells contains both the constitutive and heat-inducible forms of hsp70. Induction of p56 also occurs in IM-9 cells subjected to chemical stress (sodium arsenite). It is proposed that p56 is a steroid receptor-associated heat shock protein which can now be termed hsp56. Like hsp90, hsp56 likely serves in some vital cellular role apart from any specific function it provides in steroid receptor action. PMID- 2266109 TI - Characterization of the receptor to vasculotropin on bovine adrenal cortex derived capillary endothelial cells. AB - Recently a new growth factor was purified to homogeneity, and its bioactivity seemed to be restricted to vascular endothelial derived cells. As it was also angiogenic in vivo, it was provisionally named vasculotropin (VAS). As an iodination procedure used to label VAS did not damage the molecule, it was possible to undertake binding studies. The binding of iodinated vasculotropin to bovine adrenal cortex-derived capillary endothelial cells was saturable at 250 pM, and half-maximal binding occurred at 47 pM. Scatchard's analysis of the data demonstrated two apparent classes of binding sites with apparent dissociation constants of 2 and 82 pM displaying 280 and 3400 binding sites, respectively. The binding was specific; half-displacement was observed with a 2-fold excess of unlabeled VAS. The structurally related platelet-derived growth factor did not compete in a radioreceptor assay. 125I-VAS was displaced by suramin and not by heparin. 125I-VAS was covalently cross-linked to its cell surface receptor on intact bovine adrenal cortex-derived capillary endothelial cells using the homobifunctional agents ethylene glycol bis(succinimidyl succinate) or disuccinimidyl tartarate. A major macromolecular species with an apparent molecular mass of 230,000 Da was labeled under reducing and nonreducing conditions. These data demonstrate the existence of a specific binding protein for VAS and an estimation of the size at 185,000 Da. PMID- 2266110 TI - Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells. AB - We have cloned and sequenced a mouse cDNA encoding the 793-residue amino acid sequence of furin, which is a protein homologous to the yeast Kex2 protease. The entire sequence is 94% identical to that of human furin, and it contains the 289 residue sequence of the subtilisin-like catalytic domain. Within this region, 99, 64, and 53% of the amino acids are identical to those of human furin, human PC2 (the other mammalian Kex2-like protein), and yeast Kex2, respectively. It has been proposed that furin is a mammalian prohormone processing enzyme which cleaves precursors at paired basic amino acids, based on the fact that the Kex2 protease is responsible for processing of alpha-mating factor and killer toxin precursors at dibasic sites. However, Northern blot analysis has revealed that a furin mRNA transcript is present in all tested mouse tissues and culture cell lines, including those known not to process prohormones. Moreover, when furin and a prohormone, prorenin, have been coexpressed in mammalian cells by DNA transfection, no processing has been observed. These observations fail to show a role for furin, a Kex2-like mammalian protease, in prohormone processing. PMID- 2266111 TI - The secreted form of the epidermal growth factor receptor. Characterization and crystallization of the receptor-ligand complex. AB - A protein composed of the external domain of the epidermal growth factor (EGF) receptor is secreted by A431 human tumor cells. The soluble receptor protein was isolated in bulk quantities from cell culture supernatants. It has an intact ligand binding site, exists in a 93-kDa monomeric form, and does not undergo oligomerization upon ligand binding; thus the receptor dimerization reported for the EGF holoreceptor appears not to be a function of its external domain. The unique system of a physiological soluble receptor was utilized for a crystallization study. Crystals were obtained but only in the presence of the ligand. They contained (in equimolar amounts) receptor as well as EGF. The crystals belong to the tetragonal space group P4(3)2(1)2 or P4(1)2(1)2 with unit cell dimensions a = b = 118 A, c = 202 A. The packing density parameter was 3.55 A3/dalton, indicating the asymmetric unit to consist of one receptor-ligand complex. PMID- 2266112 TI - The extinction of erythroid genes after tetradecanoylphorbol acetate treatment of erythroleukemic cells correlates with down-regulation of the tissue-specific factors NF-E1 and NF-E2. AB - We have studied the elements involved in the tetradecanoylphorbol acetate (TPA) mediated extinction of erythroid-specific genes. We show that transcription driven by a -714/+78-base pair DNA fragment of the erythroid promoter of the human porphobilinogen deaminase gene is down-regulated upon TPA treatment of erythroleukemic cells. Examination of the DNA binding activity of trans-acting factors involved in the expression of the porphobilinogen deaminase erythroid promoter showed (i) a constitutive expression of the CACC binding proteins and (ii) a decrease in DNA binding activity of two tissue-specific factors, NF-E1 and NF-E2. Kinetics experiments indicated that NF-E2 was down-regulated after 1 h of TPA treatment whereas NF-E1 was down-regulated at the protein and mRNA levels only after 5 h of TPA treatment. These results suggest that different pathways, acting via different transcription factors, are involved in the TPA-mediated extinction of erythroid-specific genes. PMID- 2266113 TI - Rate of ATP synthesis in the perfused rat liver by 31P cryo-NMR. AB - ATP concentrations in the perfused rat liver during normoxic perfusion, transient ischemia, and recovery from transient ischemia were measured using the modified 31P cryo-NMR method (Chance, B., Nakase, Y., Bond, M., Leigh, J. S., Jr., and McDonald, G. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4925-4929). Transient ischemia was induced in the perfused livers of starved rats, and multiple freeze trapped tissue samples were taken from each liver at short intervals (15-30 s) during ischemia or following reperfusion. The freeze-trapped tissue was pulverized together with an antifreezing agent and high energy metabolites were measured by 31P NMR at 243 K after thawing. By using the cryo-NMR technique, a biochemical time resolution of 2 s could be achieved. Absolute metabolite concentrations were calculated by comparing the peak areas with internal standards mixed into the samples. Good time resolution and reliable concentration measurements provided by the cryo-NMR method enable us to estimate the ATP synthesis rate in the perfused liver during reperfusion following transient ischemia. The rate of ATP synthesis in the normoxic perfusion was 1.95 mumol/min/g wet weight; the maximal ATP synthesis rate during the recovery phase from ischemia was 5.75 mumol/min/g wet weight. PMID- 2266114 TI - Zinc-activated alcohols in ternary complexes of liver alcohol dehydrogenase. AB - Activation parameters for each reaction step in the kinetic mechanism of liver alcohol dehydrogenase have been measured for the oxidation of ethanol and the reduction of acetaldehyde. In the oxidation process, the highest enthalpy of activation, 9.7 kcal/mol, occurs for the turnover of the liver alcohol dehydrogenase-NAD(+)-ethanol ternary complex. To investigate if this enthalpy requirement represents a change in the ionization state of ethanol bound in the ternary complex, inhibition of ethanol oxidation was determined using the following series of small, electronegative alcohols with pKa values ranging from 12.37 to 15.5: 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 2,2,2 tribromoethanol, 2,2-dichloroethanol, 2,2-difluoroethanol, propargyl alcohol, 3 hydroxypropionitrile, 2-chloroethanol, 2-iodoethanol, 2-methoxyethanol, ethylene glycol, and methanol. The observed inhibition patterns were analyzed according to several kinetic inhibition models; in each case, the best fit model was used to determine the substrate competitive inhibition constant. A plot of the logarithm of these inhibition constants is shown to be dependent on the pKa values of the inhibiting alcohols with a slope approaching -1, indicating that inhibition is controlled by a proton loss from the alcohol. The observed competitive inhibition behavior, coupled with crystallographic studies depicting a direct ligation of an alcohol oxygen to the catalytic zinc ion, indicates that inhibition is controlled by the formation of a zinc-bound alkoxide. Because the inhibiting alcohols are structurally homologous to ethanol, a relationship between the inhibition constant and the inhibiting alcohol's pKa can be derived to show that the pKa of an alcohol bound in a ternary complex is also dependent on its pKa as a free alcohol. Ternary complex pKa values have been determined for ethanol and the inhibiting alcohols. PMID- 2266115 TI - Protein kinase C plays an inhibitory role in interleukin 3- and interleukin 4 mediated mast cell proliferation. AB - Interleukin 3 (IL-3) is required for the survival and proliferation of mouse bone marrow derived mast cells (BMMC). Although interleukin 4 (IL-4) has no direct effect on growth activity, it synergizes with IL-3 in promoting the growth of these cells. The intracellular mechanism by which these ligand-receptor interactions promote mast cell growth are not well documented in the literature. Here we present evidence that both IL-3 and IL-4 have been found to activate protein kinase C (PKC) and phosphatidylinositol turnover in BMMC, in a similar time- and dose-dependent manner, indicating that activation of PKC is not sufficient to induce proliferation in these cells. In this work we addressed the question as to whether the activation of PKC is necessary for mast cell proliferation. Activation of PKC by phorbol myristate acetate causes inhibition of IL-3-mediated growth for the first 72 h of incubation. The inhibition in IL-3 mediated proliferation gradually lessens with the stages of PKC depletion, which is complete after 72 h. The enhancement in phorbol myristate acetate-treated cells grows as PKC is depleted. The inactive phorbol ester, 4-alpha-phorbol, had no effect on proliferation of BMMC. Cells, PKC-depleted by chronical phorbol ester treatment, responded to IL-3 or IL-4 with a significant increase in [3H] thymidine uptake over PKC containing cells stimulated with the same lymphokine. Use of antibodies to these lymphokines showed that the enhanced response of the PKC-depleted BMMC was not due to the additional autocrine production of IL-3 or IL-4 by these cells. The PKC-depleted cells retain the capacity to return to almost normal levels of PKC activity and sensitivity to IL-3 and IL-4, after 72 and 120 h, respectively. These results indicate that PKC plays an important inhibitory role in IL-3- and IL-4-mediated proliferation of BMMC. PMID- 2266116 TI - Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth. AB - The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy. PMID- 2266117 TI - Post-translational modification of bovine pro-opiomelanocortin. Tyrosine sulfation and pyroglutamate formation, a mass spectrometric study. AB - The amino-terminal fragment of beta-lipotropin (i.e. beta-lipotropin (1-40)) and joining peptide portions of pro-opiomelanocortin have been purified from extracts of bovine posterior pituitaries. Peptides were purified using a combination of reversed-phase and ion-exchange batch extraction procedures followed by reversed phase high performance liquid chromatography. beta-Lipotropin (1-40) was found to consist of four major components while joining peptide was found to consist of two major components. Fast atom bombardment-mass spectrometric analysis of the tryptic fragments of both peptides revealed that the observed heterogeneity could be explained in terms of post-translational modifications. beta-Lipotropin (1-40) was found to be sulfated at tyrosine residue 28 to an extent of about 50%. The tyrosine residue in beta-lipotropin (1-40) is situated within an amino acid sequence with a preponderance of glutamate residues. Sulfation of this amino acid residue is entirely compatible with the known primary structure requirements of the sulfotransferase enzyme located in the trans-Golgi fraction. Both beta lipotropin (1-40) and joining peptide were found to have pyroglutamate at their amino termini to an extent of about 50%. The cDNA sequence for bovine pro opiomelanocortin predicts the presence of glutamic acid at position 1 of both peptides. Pyroglutamate is normally formed through the cyclization of glutamine. This reaction is thought to be catalyzed by a pyroglutamate forming enzyme located within the secretory granule fraction. Under certain circumstances peptides with glutamate at their amino termini may act as substrates for this enzyme. PMID- 2266118 TI - Expression of PiM-and PiZ-mutated forms of the human alpha 1-antitrypsin gene in transfected monkey COS1 cells. AB - The PiZ mutation of the gene coding for alpha 1-antitrypsin results in a serum deficiency of this protein leading to early onset emphysema and liver disease. The PiZ gene has a Z-specific point mutation in exon V together with a point mutation in exon III which is also present in some normal (PiM) individuals. There has thus far been no system to study the effects of PiZ point mutations in tissue culture. We constructed plasmids containing alpha 1-antitrypsin cDNA synthetically altered at either exon III or exon V mutation sites and linked to simian virus 40 promoter sequences. Such constructs with the exon V mutation were transfected into monkey COS1 cells followed by analysis of expression of alpha 1 antitrypsin gene products. COS1 cells normally synthesize virtually no alpha 1 antitrypsin mRNA or protein. alpha 1-Antitrypsin mRNA is transcribed at high levels in cells transfected with either M or Z plasmids. Immunologic staining of COS1 cells within 48 h of transfection localizes alpha 1-antitrypsin protein to specific regions of the cytoplasm. This extranuclear localization is also observed with human HepG2 hepatoma cells, which synthesize alpha 1-antitrypsin at high levels, and with human SK-Hep1 hepatoma cells transfected with an M plasmid. The cloned synthetically altered alpha 1-antitrypsin genes provide a system for dissecting contributions of distinct point mutations to the pathological effects of the PiZ protein. PMID- 2266119 TI - Production, properties, and thrombin inhibitory mechanism of hirudin amino terminal core fragments. AB - Hirudin, a thrombin-specific inhibitor, comprises a compact amino-terminal core domain (residues 1-52) and a disordered acidic carboxyl-terminal tail (residues 53-65). An array of core fragments were prepared from intact recombinant hirudin by deletion of various lengths of its carboxyl-terminal tail on selective enzymatic cleavage. Hir1-56 and Hir1-53 were produced by pepsin digestion at Phe56-Glu57 and Asp53-Gly54. Hir1-52 was generated by Asp-N cleavage at Asn52 Asp53. Hir1-49 was prepared by cleavage of Gln49-Ser50 by chymotrypsin, elastase, and thermolysin. In addition, Hir1-62 (containing part of the carboxyl-terminal tail) was derived from Hir1-65 by selective removal of the three carboxyl terminal amino acids using carboxypeptidase A. Hirudin amino-terminal core fragments were stable at extreme pH (1.47 and 12.6), high temperature (95 degrees C), and resistant to attack by various proteinases. For instance, following 24-h incubation with an equal weight of pepsin, the covalent structure of Hir1-52 remained intact and its anticoagulant activity unaffected. Unlike intact hirudin (Hir1-65) the inhibitory potency of which is a consequence of concerted binding of its amino-terminal and carboxyl-terminal domains to the active site and the fibrinogen recognition site of thrombin, the core fragments block only the active site of thrombin with binding constants of 19 nM (Hir1-56), 35 nM (Hir1-52), and 72 nM (Hir1-49). As an anticoagulant Hir1-56 is about 2-, 4-, and 30-fold more potent (on a molar basis) than Hir1-52, Hir1-49, and Hir1-43, respectively. Hir1 56 was also about 15-fold more effective than the most potent carboxyl-terminal fragment of hirudin, sulfated-Hir54-65, although they bind to independent sites on thrombin. The potential advantages of hirudin core fragments as antithrombotic agents are discussed in this report. PMID- 2266120 TI - Structural and functional properties of the 14-kDa envelope protein of vaccinia virus synthesized in Escherichia coli. AB - Vaccinia virus is a highly cytocidal virus, but the steps that lead to virus penetration into cells, the first event in virus pathogenesis, have not been elucidated. We have shown that a 14-kDa envelope protein of vaccinia virus might play a major role in virus-penetration acting at the level of cell fusion (Rodriguez, J. F., Paez, E., and Esteban, M. (1987) J. Virol. 61, 395-404; Gong, S., Lai, C., and Esteban, M. (1990) Virology 178, 81-91). To carry out structural and functional studies on the vaccinia 14-kDa protein, it would be desirable to have a high level expression system, since the amount of protein that can be obtained from purified virus or from infected cells is very limited. In this investigation we demonstrate that the 14-kDa envelope protein of vaccinia virus is expressed in Escherichia coli in soluble form and at high levels. We establish, by several criteria, that the 14-kDa vaccinia virus protein expressed in E. coli is similar to the protein found in the virus particle based on apparent molecular mass, occurrence of disulfide-linked oligomers, reactivity against specific monoclonal antibody, and identity in amino-terminal sequence with the predicted DNA sequence of the gene. We define several structural and functional properties concerning the 14-kDa envelope protein of vaccinia virus. 1) 14 kDa is a trimer of identical subunits. 2) A monomer binds to itself more strongly than to a dimer or a trimer. 3) Oligomerization does not require cellular factors. 4) Trimers induce high titer neutralizing antibodies in animals which correlate with overall immunogenicity. 5) 14-kDa binds with specificity to the cell surface of cultured cells. PMID- 2266121 TI - Gentisate 1,2-dioxygenase from Pseudomonas. Substrate coordination to active site Fe2+ and mechanism of turnover. AB - Gentisate 1,2-dioxygenase catalyzes the oxygenolytic ring cleavage of gentisate (2,5-dihydroxybenzoate) between carbons 1 and 2 to form maleylpyruvate. The essential active site Fe2+ of the enzyme binds NO to yield an EPR-active (S = 3/2) complex. Hyperfine broadening from 17O (I = 5/2) is observed in the spectrum of the enzyme-nitrosyl complex prepared in 17O-enriched water, demonstrating that water is an iron ligand. Association of gentisate with the enzyme-nitrosyl complex causes the broadening due to [17O]water to disappear, suggesting that water is displaced. Hyperfine broadening of the EPR spectrum for the gentisate bound complex is observed when 17O is incorporated into either the carbon 1 carboxylate or carbon 2 hydroxyl substituents of gentisate, but not when it is placed in the carbon 5 hydroxyl substituent. Thus, substrate apparently binds directly to the iron through the carbon 1 carboxylate and carbon 2 hydroxyl substituents, thereby bringing the site of ring cleavage close to the active site iron. Since NO must bind to the iron to elicit an EPR signal, a total of three sites in the iron coordination appear to be available for exogenous ligands. The role of the substrate functional groups in catalysis is investigated through comparison of the reaction kinetics of gentisate analogs using the gentisate 1,2 dioxygenases isolated from Pseudomonas acidovorans and Pseudomonas testosteroni. Turnover is either eliminated or substantially reduced on replacement of any of the functional groups of gentisate. Furthermore, an electron-donating group that can tautomerize (hydroxyl or amine) is required in a ring position either ortho or para to the carbon 2 substituent for turnover. The best alternate substrate of this group is 5-aminosalicylate, which is turned over at approximately 7% of the rate of gentisate by the enzyme from P. testosteroni. Both atoms from O2 are shown to be incorporated into the product of 5-aminosalicylate turnover. This is the first direct demonstration of dioxygenase stoichiometry in the reaction of any ferrous, non-heme, aromatic ring-cleaving dioxygenase. It is proposed that the enzyme-catalyzed O2 attack on the aromatic ring of gentisate is initiated from a complex in which O2 and substrate are simultaneously coordinated to the active site iron. Subsequent dioxygen bond cleavage and insertion are proposed to be promoted by a resonance shift involving ketonization of the carbon 5 hydroxyl group. PMID- 2266122 TI - Expression of sodium-linked nucleoside transport activity in monolayer cultures of IEC-6 intestinal epithelial cells. AB - Mature, confluent monolayer cultures of IEC-6 rat intestinal epithelial cells in conventional growth media express both Na(+)-linked, concentrative nucleoside transport (NT) activity and equilibrative, inhibitor-sensitive NT activity, but do not show morphologic differentiation. Na(+)-dependent fluxes of Ado and formycin B were minor in early subconfluent IEC-6 monolayers, but increased severalfold to become the major component of influx of these agents in confluent monolayers grown in medium containing Nu-Serum, a commercial medium supplement with a low serum content. In monolayers cultured in medium with fetal bovine serum, cell proliferation rates were similar to those in medium supplemented with Nu-Serum, but expression of Na(+)-linked NT activity was 6-8-fold lower than in monolayers grown in the latter medium. Inclusion of hydrocortisone in growth medium with Nu-Serum caused a 2-fold increase in the expression of Na(+)-linked NT activity. Experiments in which components of medium supplementation were withheld showed that insulin and epidermal growth factor were important in expression of the Na(+)-linked NT activity. Because the Na(+)-linked NT system has a brush border location in fresh intestinal epithelium, it is concluded that the regulated expression of this activity in the IEC-6 monolayers is a differentiative change. PMID- 2266123 TI - Acylation of exogenous glycosylsphingosines by intact neuroblastoma (NCB-20) cells. AB - Acylation of exogenously added galactosylsphingosine was demonstrated in intact NCB-20 neuroblastoma cells, a cell line that normally does not synthesize galactosylceramide. Labeling of cells with [3H]palmitic acid for 6 h in the presence of 100 microM exogenous galactosylsphingosine (GalSph) resulted in a more than 3-fold increase in the incorporation of label into the ceramide monohexoside fraction relative to controls. This increase, which was almost entirely due to the incorporation of labeled nonhydroxy fatty acid into galactosylceramide, was linear over a concentration range of 1-100 microM galactosylsphingosine and for the first 5 h after the addition of galactosylsphingosine. Similarly, the addition of 100 microM glucosylsphingosine resulted in a 3-fold increase of label incorporated into glucosylceramide. Incubation of cells with 100 microM GalSph and labeled fatty acids of various chain lengths revealed that the acylation of GalSph was specific for medium chain (C16-C18) nonhydroxy fatty acids, suggesting that this was an enzyme-mediated reaction. The enzymatic nature of GalSph acylation was further demonstrated when cells were incubated for 72 h with 15 microM [3H]galactosylsphingosine labeled in the galactose moiety. [3H]Galactosylceramide containing only medium chain non hydroxy fatty acids accumulated linearly with time reaching a maximum at 48 h and was observed to be further metabolized to ceramide dihexoside. This acylation reaction may be potentially important for the removal of glycosylsphingosines in the cell. PMID- 2266124 TI - Effect of bradykinin on Na-K-2Cl cotransport and bumetanide binding in aortic endothelial cells. AB - Simultaneous measurements of potassium influx and binding of [3H]bumetanide were performed in endothelial cells cultured from bovine aortas to determine how bradykinin regulates Na-K-2Cl cotransport. [3H]Bumetanide displayed saturable binding and was displaced by low concentrations of unlabeled bumetanide. All three transported ions were required for binding and high concentrations of chloride inhibited binding, consistent with binding of bumetanide to the second chloride site of the transporter. Scatchard analysis of binding under maximal conditions (100 mM sodium, 30 mM potassium, 30 mM chloride) revealed a single class of binding sites with a binding constant of 112 nM and a density of 22 fmol/cm2 or approximately 122,000 sites/cells. Na-K-2Cl cotransport, measured as bumetanide-sensitive potassium influx, was stimulated 118 +/- 30% by bradykinin (p less than 0.01) at physiologic ion concentrations. Stimulation was inhibited by increased potassium or decreased external chloride concentrations and was not seen in conditions required for maximal binding of bumetanide. Simultaneous measurement of the binding of tracer [3H]bumetanide and its inhibition of potassium influx in medium containing 10 mM potassium and 130 mM chloride revealed a turnover number for the cotransporter of 293 +/- 68 s-1 which increased to 687 +/- 105 s-1 with bradykinin (p less than 0.001). There was no change in cell volume and only a 5.6 mM increase in intracellular sodium concentration associated with this stimulation. Bradykinin also increased the affinity of the cotransporter for bumetanide as indicated by a decrease in the Ki for potassium influx from 464 +/- 46 nM to 219 +/- 19 nM (p less than 0.005). Our results show that [3H]bumetanide can be used to quantitate Na-K-2Cl cotransporter sites in aortic endothelial cells and to determine the mechanism by which cotransport is regulated. The stimulation of cotransport in aortic endothelial cells by bradykinin is due to an increase in the activity of existing transporters rather than to an increase in the number of transporters. This, together with the increased affinity for bumetanide, strongly suggests that a change in cotransporter structure is occurring in response to bradykinin. PMID- 2266125 TI - 4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase. AB - A variety of alkyl-substituted 4-aminobutanoic acid derivatives, including a homologous series of 3-alkyl-4-aminobutanoic acid analogues, 4-methyl isomer analogues, the 3,3-dimethyl analogue, and (E)-4-amino-3-methyl-2-butenoic acid, were synthesized and tested as alternate substrates for purified gamma aminobutyric acid aminotransferase from pig brain. All of the compounds were substrates, but their activities diminished as the size and bulk of the 3-alkyl substituent increased. Several differences were observed between the alkyl substituted analogues and the corresponding aryl-substituted compounds previously reported (Silverman, R. B., Invergo, B. J., and Levy, M. A. (1987) J. Biol. Chem. 262, 3192-3195). These findings will be important in future designs of inhibitors of gamma-aminobutyric acid aminotransferase. PMID- 2266126 TI - Interaction of the Mnt repressor with 37-base pair synthetic operator DNA fragments. Importance of symmetric GC pairs. AB - Mnt repressor is indirectly responsible for the maintenance of lysogeny of the phage P22. This repressor interacts with a 21-base pair operator DNA constituting within it a 17-base pair perfect 2-fold symmetric sequence whose bases make a direct contact with the protein. We have synthesized six 37-base pair DNAs consisting of 21 base pair natural operator and its modifications in which certain symmetrically situated GC base pairs were replaced systematically with ATs to understand their importance. The binding interaction studies of Mnt repressor to such natural and modified operator DNAs reported here indicate that the GCs close to the center of symmetry make major contacts with the protein whereas, GCs nearer to the periphery form weak contacts. Methylation protection experiments indicated that when the GCs near the center of symmetry were replaced with AT, the central GC became more accessible for dimethyl sulfate methylation with possible conformational change in DNA. The circular dichroism studies indicated that upon repressor binding conformational changes in DNA takes place with a possible increase in helicity of the repressor protein. PMID- 2266127 TI - Surplus acylcarnitines in the plasma of starved rats derive from the liver. AB - The method used here to assess the contribution of liver to plasma acylcarnitine is based on the idea that in rat, shortly after administration of [3H]butyrobetaine the [3H]carnitine appearing in the plasma derives from the liver and so does the acyl moiety of [acyl-3H] carnitine. In the perchloric acid extracts of plasma and liver, the ester fraction of total carnitine was determined by enzymatic analysis and that of [3H]carnitines was determined by high performance liquid chromatography. The ester fraction of total carnitine in the plasma of fed rats was 32.6% while that of [3H]carnitines was 67.9%, 1 h following injection of [3H]butyrobetaine. For 48 h starved rats the equivalent values were 54.2 and 84.0%, respectively. 24 h after the administration of [3H]butyrobetaine, the ester content became the same in the total and [3H]carnitines. That the newly synthesized carnitine was more acylated (67.9 versus 32.6%, fed) indicates that liver exports acyl groups with carnitine as carrier. The observation that the ester fraction in the newly synthesized plasma carnitine increased with fasting (84.0 versus 67.9%) indicates that the surplus plasma acylcarnitine in fasting ketosis derives from the liver. Perfused livers, however, released carnitine with the same ester content (60-61%) whether they were from fed or fasted animals. Probably, the increased plasma [acylcarnitine] in fasting develops not by an increased ester output from the liver but by an altered handling in extrahepatic tissues. PMID- 2266128 TI - Spermidine biosynthesis in Saccharomyces cerevisiae. Biosynthesis and processing of a proenzyme form of S-adenosylmethionine decarboxylase. AB - We have cloned and sequenced the Saccharomyces cerevisiae gene for S adenosylmethionine decarboxylase. This enzyme contains covalently bound pyruvate which is essential for enzymatic activity. We have shown that this enzyme is synthesized as a Mr 46,000 proenzyme which is then cleaved post-translationally to form two polypeptide chains: a beta subunit (Mr 10,000) from the amino terminal portion and an alpha subunit (Mr 36,000) from the carboxyl-terminal portion. The protein was overexpressed in Escherichia coli and purified to homogeneity. The purified enzyme contains both the alpha and beta subunits. About half of the alpha subunits have pyruvate blocking the amino-terminal end; the remaining alpha subunits have alanine in this position. From a comparison of the amino acid sequence deduced from the nucleotide sequence with the amino acid sequence of the amino-terminal portion of each subunit (determined by Edman degradation), we have identified the cleavage site of the proenzyme as the peptide bond between glutamic acid 87 and serine 88. The pyruvate moiety, which is essential for activity, is generated from serine 88 during the cleavage. The amino acid sequence of the yeast enzyme has essentially no homology with S adenosylmethionine decarboxylase of E. coli (Tabor, C. W., and Tabor, H. (1987) J. Biol. Chem. 262, 16037-16040) and only a moderate degree of homology with the human and rat enzymes (Pajunen, A., Crozat, A., Janne, O. A., Ihalainen, R., Laitinen, P. H., Stanley, B., Madhubala, R., and Pegg, A. E. (1988) J. Biol. Chem. 263, 17040-17049); all of these enzymes are pyruvoyl-containing proteins. Despite this limited overall homology the cleavage site of the yeast proenzyme is identical to the cleavage sites in the human and rat proenzymes, and seven of the eight amino acids adjacent to the cleavage site are identical in the three eukaryote enzymes. PMID- 2266129 TI - Delta-bag cell peptide from the egg-laying hormone precursor of Aplysia. Processing, primary structure, and biological activity. AB - The bag cells of the marine mollusk Aplysia express a gene encoding a 271-residue egg-laying hormone (ELH) precursor that is processed into at least nine peptide products. Four of the peptides have been identified in bag cell releasates and are known to act as nonsynaptic neurotransmitters in the abdominal ganglion. The isolation, primary structure, and proposed biological activity of a fifth peptide product (delta-bag cell peptide (delta-BCP)) from the ELH precursor are described. delta-BCP was established to be a 39-residue peptide: NH2-Asp-Gln-Asp Glu-Gly-Asn-Phe-Arg-Arg-Phe-Pro-Thr-Asn-Ala-Val-Ser-Met- Ser-Ala-Asp- Glu-Asn-Ser Pro-Phe-Asp-Leu-Ser-Asn-Glu-Asp-Gly-Ala-Val-Tyr-Gln-Arg- Asp-Leu-COOH. This sequence corresponds to residues 81-119 of the ELH prohormone and shares sequence identity with atrial gland peptides A and B. Significantly, synthetic delta-BCP stimulated Ca2+ uptake into mitochondria of secretory cells in the albumin gland in vitro, suggesting that the peptide regulates the cellular release of perivitelline fluid by the gland. Similar results were obtained with purified peptide A and a shorter version of delta-BCP (delta-BCP-(14-33)). These results indicate that delta-BCP belongs to a family of structurally related peptides with similar pharmacological activities that center at a conserved region of sequence corresponding to delta-BCP-(14-33). PMID- 2266130 TI - Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. AB - Although angiotensin II (Ang II)-forming enzymatic activity in the human left cardiac ventricle is minimally inhibited by angiotensin I (Ang I) converting enzyme inhibitors, over 75% of this activity is inhibited by serine proteinase inhibitors (Urata, H., Healy, B., Stewart, R. W., Bumpus, F. M., and Husain, A. (1990) Circ. Res. 66, 883-890). We now report the identification and characterization of the major Ang II-forming, neutral serine proteinase, from left ventricular tissues of the human heart. A 115,150-fold purification from human cardiac membranes yielded a purified protein with an Mr of 30,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based upon its amino-terminal sequence, the major human cardiac Ang II-forming proteinase appears to be a novel member of the chymase subfamily of chymotrypsin-like serine proteinases. Human heart chymase was completely inhibited by the serine proteinase inhibitors, soybean trypsin inhibitor, phenylmethylsulfonyl fluoride, and chymostatin. It was partially inhibited by p-tosyl-L-phenylalanine chloromethyl ketone, but was not inhibited by p-tosyl-L-lysine chloromethyl ketone, and aprotinin. Also, human heart chymase was not inhibited by inhibitors of the other three classes of proteinases. Human heart chymase has a high specificity for the conversion of Ang I to Ang II and the Ang I-carboxyl-terminal dipeptide His-Leu (Km = 60 microM; Kcat = 11,900 min-1; Kcat/Km = 198 min-1 microM-1). Human heart chymase did not degrade several peptide hormones, including Ang II, bradykinin, and vasoactive intestinal peptide, nor did it form Ang II from angiotensinogen. The high substrate specificity of human heart chymase for Ang I distinguishes it from other Ang II-forming enzymes including Ang I converting enzyme, tonin, kallikrein, cathepsin G, and other known chymases. PMID- 2266131 TI - Glycosaminoglycan-mediated leuserpin-2/thrombin interaction. Structure-function relationships. AB - Two recently identified structural elements important for glycosaminoglycan mediated activation of human leuserpin-2 (hLS2) were investigated in detail by functional analysis of variants secreted by transiently transfected COS cells. Highly specific requirements with respect to the nature of the involved amino acids as well as to their spatial arrangements were found to be crucial for efficient activation of hLS2 by dermatan sulfate. In contrast, binding and activation of hLS2 by heparin seem to be determined mainly by the positive charge density of the involved inhibitor segment. A dimeric repeat enriched in acidic amino acids turned out to exert a dual role with respect to structure and function of hLS2. First, in the absence of functional activators the negatively charged dimer interacts intramolecularly with the glycosaminoglycan-binding site. Second, the acidic dimer is instrumental in glycosaminoglycan-mediated activation of hLS2. The monomers constituting the acidic dimer are functionally not equivalent. PMID- 2266132 TI - Cryoelectron microscopy of frozen-hydrated alpha-ketoacid dehydrogenase complexes from Escherichia coli. AB - The native architectures of the pyruvate and 2-oxoglutarate dehydrogenase complexes have been investigated by cryoelectron microscopy of unstained, frozen hydrated specimens. In pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex the transacylase (E2) components exist as 24-subunit, cube shaped assemblies that form the structural cores of the complexes. Multiple copies (12-24) of the alpha-ketoacid dehydrogenase (E1) and dihydrolipoyl dehydrogenase (E3) components bind to the surface of the cores. Images of the frozen-hydrated enzyme complexes do not appear consistent with a symmetric arrangement of the E1 and E3 subunits about the octahedrally symmetric E2 core. Often the E1 or E3 subunits appear separated from the surface of the E2 core by 3 5 nm, and sometimes thin bridges of density appear in the gap between the E2 core and the bound subunits; studies of subcomplexes consisting of the E2 core from 2 oxoglutarate dehydrogenase complex and E1 or E3 show that both E1 and E3 are bound in this manner. Images of the E2 cores isolated from pyruvate dehydrogenase complex appear surrounded by a faint fuzz that extends approximately 10 nm from the surface of the core and likely corresponds to the lipoyl domains of the E2. PMID- 2266133 TI - A novel pathway of import of alpha-mannosidase, a marker enzyme of vacuolar membrane, in Saccharomyces cerevisiae. AB - We have investigated the vacuolar delivery of alpha-mannosidase, a marker enzyme of the vacuolar membrane in the yeast Saccharomyces cerevisiae, and found that the enzyme has several unique characteristics in its biosynthesis and vacuolar delivery. alpha-Mannosidase has no typical signal sequence (Yoshihisa, T., and Anraku, Y. (1989) Biochem. Biophys. Res. Commun. 163, 908-915) but is located on the inner surface of the vacuolar membrane. The enzyme is synthesized as a 107 kDa polypeptide and converted to a 73-kDa polypeptide. Although the conversion depends on a vacuolar processing protease, proteinase A, it is much slower (t1/2 = 10 h) than the proteinase A-dependent processing of other vacuolar proteins. None of Asn-X-Thr/Ser sites on the 107-kDa alpha-mannosidase or on two alpha mannosidase-invertase fusion proteins that are localized inside the vacuole receives N-linked oligosaccharide, whereas those sites on a carboxypeptidase Y alpha-mannosidase fusion protein are N-glycosylated. The newly synthesized alpha mannosidase is normally delivered to the vacuole and converted to the 73-kDa polypeptide even when the secretory pathway is blocked by a subset of sec mutations. These characteristics are different from those of other vacuolar proteins targeted to the vacuole via the secretory pathway. We conclude that alpha-mannosidase is delivered to the vacuole in a novel pathway separate from the secretory pathway. PMID- 2266134 TI - Proclotting enzyme from horseshoe crab hemocytes. cDNA cloning, disulfide locations, and subcellular localization. AB - Proclotting enzyme is an intracellular serine protease zymogen closely associated with an endotoxin-sensitive hemolymph coagulation system in limulus. Its active form, clotting enzyme, catalyzes conversion of coagulogen to insoluble coagulin gel. We present here the cDNA and amino acid sequences, disulfide locations, and subcellular localization of proclotting enzyme. The isolated cDNA for proclotting enzyme consists of 1,501 base pairs. The open reading frame of 1,125 base pairs encodes a sequence comprising 29 amino acid residues of prepro-sequence and 346 residues of the mature protein with a molecular mass of 38,194 Da. Three potential glycosylation sites for N-linked carbohydrate chains were confirmed to be glycosylated. Moreover, the zymogen contains six O-linked carbohydrate chains in the amino-terminal light chain generated after activation. The cleavage site that accompanies activation catalyzed by trypsin-like active factor B, proved to be an Arg-Ile bond. The resulting carboxyl-terminal heavy chain is composed of a typical serine protease domain, with a sequence similar to that of human coagulation factor XIa (34.5%) or factor Xa (34.1%). The light chain has a unique disulfide-knotted domain which shows no significant homology with any other known proteins. Thus, this proclotting enzyme has a mammalian serine protease domain and a structural domain not heretofore identified in coagulation and complement factors. Immunohistochemical studies showed that the proclotting enzyme is localized in large granules of hemocytes. PMID- 2266135 TI - A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin. AB - Protein kinase C (PKC)-related cDNA clones isolated from mouse epidermis cDNA library encoded a 78-kDa protein, nPKC eta. nPKC eta contains a characteristic cysteine-rich repeat sequence (C1 region) and a protein kinase domain sequence (C3 region), both of which are conserved among PKC family members. However, nPKC eta lacks a putative Ca2+ binding region (C2 region) that is seen in conventional PKCs (alpha, beta I, beta II, gamma), but not in novel PKCs (nPKC delta, epsilon, -zeta). nPKC eta shows the highest sequence similarity to nPKC epsilon (59.4% identity). The similarity extends to the NH2-terminal sequence (E region) which corresponds to one of the divergent regions (D1 region). Northern blot analysis showed that the mRNA for nPKC eta is highly expressed in the lung and skin but, in contrast to other members of the PKC family, only slightly expressed in the brain. nPKC eta expressed in COS cells shows phorbol ester binding activity with a similar affinity to nPKC epsilon. Antiserum raised against a COOH terminal peptide of nPKC eta identified an 82-kDa protein in mouse lung extract as well as in an extract from COS cells transfected with the nPKC eta-cDNA expression plasmid. Autophosphorylation of nPKC eta immunoprecipitated with the specific antiserum was observed, indicating that nPKC eta is a protein kinase. These results clearly demonstrate the existence and the possible importance of nPKC eta as a member of the phorbol ester receptor/protein kinase, PKC, family. PMID- 2266136 TI - Apolipoprotein B mRNA editing. Direct determination of the edited base and occurrence in non-apolipoprotein B-producing cell lines. AB - In humans, apolipoprotein (apo) B48 is synthesized in the intestine as an obligatory constituent of chylomicrons. Apolipoprotein B48 is identical to the amino-terminal 2152 amino acids (240 kDa) of apoB100 and is translated from an edited apoB mRNA in which codon 2153 has been converted from glutamine (CAA) to what is recognized as a premature stop codon (UAA). To determine whether the apoB mRNA editing in fact converts cytosine 6666 in codon 2153 to uracil, we incubated a synthetic apoB RNA containing 32P-labeled cytosines in an in vitro editing system prepared from rabbit enterocytes. The in vitro edited RNA was purified and digested to nucleoside 5'-monophosphates, which were analyzed on two-dimensional thin-layer chromatography. We found that the edited base co-migrated with authentic uridine 5'-monophosphate. Thus, cytosine 6666 is converted to uracil, most likely by a nucleotide-specific cytosine deaminase. To determine whether apoB mRNA editing occurs in cell lines that do not synthesize apoB, we stably transfected a high expression vector containing 354 base pairs of apoB sequence into 18 different cell lines. We found apoB mRNA editing activity in five osteosarcoma cell lines and one epidermoid cell line, none of which synthesizes any detectable apoB. Thus, apoB mRNA editing occurs in cell lines that do not synthesize apoB, which suggests that mRNA editing may be a common biological phenomenon in eukaryotic cells. PMID- 2266137 TI - Apolipoprotein C-I modulates the interaction of apolipoprotein E with beta migrating very low density lipoproteins (beta-VLDL) and inhibits binding of beta VLDL to low density lipoprotein receptor-related protein. AB - The binding of native rabbit beta-very low density lipoproteins (beta-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of beta-VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit beta-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the beta-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the beta-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the beta-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP. PMID- 2266138 TI - Demonstration of binding components specific for 7,8-disubstituted guanine ribonucleosides in murine B lymphocytes. AB - 7,8-Disubstituted guanine ribonucleosides are known to be potent intracellular modulators of immune responses. These compounds trigger and modulate a wide variety of lymphocyte responses including effects exerted directly on B cells. However, little is known about their mechanism of action. The current paper describes studies undertaken to evaluate whether binding components specific for these bioactive molecules exist in splenic B lymphocytes. After exposure of cells to labeled nucleoside, two different pools of nucleoside can be distinguished: a rapidly exchangeable nucleoside pool and a slowly exchangeable pool. The material in the latter pool consists of authentic unaltered nucleoside that is complexed to a relatively hydrophobic cellular component with an apparent Mr of 30,000 40,000; binding appears to interfere with free interaction of the nucleoside's cis hydroxyls with a boronate affinity resin. The slowly exchangeable nucleoside pool is seen to localize predominantly to the nucleus in electron microscopic autoradiographs. This pool is maximally bound by 30 min of incubation. Specific, saturable binding is demonstrable, with an apparent Kd of approximately 7 microM. This value correlates well with concentrations at which half-maximal biological activity occurs and suggests that the binding component likely mediates antigen dependent immunomodulatory activity. Splenic B cells express approximately 2 x 10(4) binding sites/cell, whereas thymic lymphocytes, which do not respond functionally to nucleosides, do not display a measurable number of nucleoside binding sites. Ligand specificity of the binding interaction is confirmed by binding inhibition studies, in which binding inhibitory activity of unlabeled agonistic structural analogs recapitulate their degree of immunobiological activity. These data are most consistent with the existence of a saturable binding component with apparent specificity for 7,8-disubstituted guanine ribonucleosides in splenic B cells. PMID- 2266139 TI - Purification and molecular cloning of the "A" chain of a rat heteromeric CCAAT binding protein. Sequence identity with the yeast HAP3 transcription factor. AB - CCAAT-binding factor (CBF) is a heteromeric mammalian transcription factor which binds to sequences containing a CCAAT motif in a number of promoters such as those for type I collagen, albumin, MHC Class II, beta-actin, and others. It consists of two different components that are both needed for DNA binding. We have purified the "A" chain of CBF to apparent homogeneity by sequence-specific DNA affinity chromatography followed by Mono S and Mono Q ion-exchange chromatography and obtained the amino acid sequences of tryptic peptides of this polypeptide. Amino acid sequences of two of these tryptic peptides were used to synthesize oligonucleotide primers. The primers served to obtain a small cDNA by the polymerase chain reaction method, which was then further used to obtain larger cDNA clones. DNA sequence analysis of a representative cDNA clone revealed the presence of an open reading frame of 207 amino acids coding for a putative polypeptide of 25 kDa. Transcription of these cDNAs in vitro followed by translation in a reticulocyte lysate produced a polypeptide that migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the same mobility as the native A chain. The deduced amino acid sequence of the A chain showed a remarkable identity over a length of 90-amino acid residues with a sequence of the Hap3 polypeptide, a component of a heteromeric multisubunit yeast transcription factor. PMID- 2266140 TI - Construction and processing of transfer RNA precursor models. AB - Several "dimeric" tRNA molecules were constructed as potential substrates for ribonuclease P (RNase P) and for M1 RNA, the catalytic subunit of RNase P. Construction was affected by the T4 RNA ligase-mediated coupling of a mature Escherichia coli tRNA (acceptor substrate) and nucleotides 1-36 of yeast tRNAPhe (donor substrate), followed by annealing of the 3'-half of yeast tRNAPhe (nucleotides 38-76). E. coli RNase P and M1 RNA were both found to cleave the dimeric tRNA precursor model constructed from E. coli tRNAPhe (5'-tRNA) and yeast tRNAPhe (3'-tRNA) in a reaction that was dependent on the presence of the annealed 3'-half molecule derived from yeast tRNAPhe, or on some conformation imposed by the presence of this species; the product had the same mobility as authentic E. coli tRNAPhe on a polyacrylamide gel. By utilizing tRNA precursor models radiolabeled at phosphodiesters immediately preceding or following the putative site of processing, cleavage of the substrate by both M1 RNA and the holoenzyme was demonstrated to occur at the expected phosphate ester linkage. The results obtained here suggest that the endonucleolytic separation of two tRNAs by RNase P is dependent on one or more structural features in the 3'-half of the 3' tRNA, and thus are consistent with the report of McClain et al. (McClain, W. H., Guerrier-Takada, C., and Altman, S. (1987) Science 238, 527-530) that identifies the T stem and loop as a possible recognition site. PMID- 2266141 TI - Metal ion and substrate structure dependence of the processing of tRNA precursors by RNase P and M1 RNA. AB - A synthetic tRNA precursor analog containing the structural elements of Escherichia coli tRNA(Phe) was characterized as a substrate for E. coli ribonuclease P and for M1 RNA, the catalytic RNA subunit. Processing of the synthetic precursor exhibited a Mg2+ dependence quite similar to that of natural tRNA precursors such as E. coli tRNA(Tyr) precursor. It was found that Sr2+, Ca2+, and Ba2+ ions promoted processing of the dimeric precursor at Mg2+ concentrations otherwise insufficient to support processing; very similar behavior was noted for E. coli tRNA(Tyr). As noted previously for natural tRNA precursors, the absence of the 3'-terminal CA sequence in the synthetic precursor diminished the facility of processing of this substrate by RNase P and M1 RNA. A study of the Mg2+ dependence of processing of the synthetic tRNA dimeric substrate radiolabeled between C75 and A76 provided unequivocal evidence for an alteration in the actual site of processing by E. coli RNase P as a function of Mg2+ concentration. This property was subsequently demonstrated to obtain (Carter, B. J., Vold, B.S., and Hecht, S. M. (1990) J. Biol. Chem. 265, 7100 7103) for a mutant Bacillus subtilis tRNAHis precursor containing a potential A-C base pair at the end of the acceptor stem. PMID- 2266142 TI - A single amino acid substitution in the A subunit of Escherichia coli enterotoxin results in a loss of its toxic activity. AB - A plasmid encoding a mutant gene of heat-labile enterotoxin (LT), produced by enterotoxigenic Escherichia coli, was induced by treatment of plasmid EWD 299 with hydroxylamine. A mutant strain of E. coli HB 101 carrying the mutant plasmid pTUH 6A produced a low toxic LT analogue (mutant LT), which was cross-reactive with anti-LT antibody. The mutant LT activity was less than 0.15 and 0.006% of the normal LT in the rabbit ileal loop test and in the rabbit skin permeability test, respectively. The amino acid composition of the mutant LT-B subunit was the same as that of the normal B subunit. Though the A2 fragment of the mutant LT was identical to normal LT by DNA analysis, the A1 fragment of the mutant LT differed from the normal A1 fragment in one amino acid at position 112; namely it had lysine instead of glutamic acid from the N terminus. These data suggest that glutamic acid at position 112 from the N terminus of the A1 fragment is important for the A subunit to express its biological activity. PMID- 2266143 TI - Stage-dependent changes in localization of a germ cell-specific lamin during mammalian spermatogenesis. AB - We had earlier identified a 110/120-kDa protein specific to nuclear matrix of rat pachytene spermatocytes (Behal, A., Prakash, K., and Rao, M.R.S. (1987) J. Biol. Chem. 262, 10898-10902). This protein is now shown to be a disulfide-linked homodimer of a 60-kDa polypeptide. Indirect immunofluorescence and Western blot analyses using anti-120-kDa polyclonal antibodies have shown that this protein is a component of the pore-complex lamina structure of spermatogonia. As germ cells enter meiotic prophase and the lamina structure disassembles, this polypeptide is redistributed in the nucleus and can be isolated as a component of synaptonemal complexes. Following meiotic division, this 60-kDa protein is relocalized in the lamina, then representing the sole major component of the lamina structure of round spermatids. The identity of the 60-kDa protein in the pore-complex lamina fraction and synaptonemal complexes was further confirmed by two-dimensional analysis of iodinated tryptic peptides. Such an analysis has also shown that the germ cell-specific 60-kDa protein is related but not identical to somatic lamin B. PMID- 2266145 TI - Polymerase chain reaction for probe synthesis and for direct amplification in detection of bovine coronavirus. AB - The polymerase chain reaction (PCR) was used to synthesize ds and ss probes for the detection of bovine coronavirus (BCV) using recombinant plasmids as template molecules. The ds probes detected a minimum of about 2 X 10(5) viral genomes after exposure for 1 h, a detection limit similar to nick-translated probes after exposure of the films for 60 h. More than 8 h exposure to blots probed with these ds probes resulted in complete darkening of the film. The ss probes, synthesized by asymmetric PCR on linearized plasmids, permitted the detection of 5 X 10(4) genomes, which equalled the capacity of random-primed probes. Prolonged exposure did not increase the background as in case of ds PCR-probed blots. Probes, synthesized by asymmetric PCR and random-priming were labeled to similar specific activities and were better in terms of sensitivity and detectability as opposed to nick-translated probes. However, the specificity of detection with ss probes as to random primed probes was increased further. About 10 viral genomes, after fragment-specific amplification by PCR, were detected by agarose-gel analysis. PCR-probe synthesis was simple, highly reproducible, and allowed the synthesis of probes for specific fragments. PMID- 2266144 TI - Photolabeling of the 6 and 10 S conformations of gizzard myosin with 3'(2')-O-(4 Benzoyl)benzoyl-ATP. Proline 324 is near the active site. AB - 3'(2')-O-(4-Benzoyl)benzoyl-ATP (Bz2ATP) was used as a photoaffinity label of the ATP binding site of unphosphorylated chicken gizzard myosin. Specific photolabeling of the active site of 6 S myosin was assured by forming a stable myosin.Co(II)Bz2ADP.orthovanadate complex (termed trapping) prior to irradiation. Co2+ was used in place of Mg2+ to prevent the known photoreaction of vanadate with myosin which destabilizes the trapped complex. [3H] Bz2ADP.Pi was also stably trapped on gizzard myosin by forming the 10 S folded conformation of the protein in the presence of [3H]Bz2ATP and Mg2+. Irradiation of 6 S myosin containing orthovanadate trapped [3H] Bz2ADP or 10 S trapped [3H]Bz2ADP.Pi gave 32 and 30% covalent incorporation, respectively. The 50-kDa and precursor 68-kDa tryptic peptides of the subfragment-1 heavy chain derived from both forms of myosin were found to contain essentially all of the covalently attached [3H]Bz2ADP. Parallel experiments with untrapped [3H]Bz2ADP showed extensive nonspecific labeling of all of the major tryptic peptides and the light chains. Eight labeled peptides, isolated from 6 and 10 S photolabeled myosin, contained the sequence G319-H-V-P-I-X-A-Q326, where X corresponds to labeled proline 324. [14C]Bz2ADP was previously shown to label serine 324 in skeletal subfragment-1 (Mahmood, R., Elzinga, M., and Yount, R. G. (1989) Biochemistry 28, 3989-3995), which corresponds to alanine 325 in the gizzard sequence. Thus, this region of the 50-kDa tryptic fragment, near the nucleotide binding site, in both skeletal and smooth muscle myosins, must fold in essentially the same manner. PMID- 2266146 TI - An indirect sandwich ELISA utilising F(ab')2 fragments for the detection of African horsesickness virus. AB - African horsesickness virus (AHSV), an important disease of equines is caused by an orbivirus. Because of the need to contain the spread of the disease, it is often essential to make a rapid diagnosis. For this purpose, an ELISA capable of detecting viral antigen in animal tissue and in cell culture fluid was developed. Immobilised F(ab')2 fragments prepared by digestion of AHSV-specific IgG with pepsin were used to trap virus from tissue homogenates or cell culture supernatant. After addition of intact IgG as detecting antibody, Staphylococcus aureus protein A labelled with horseradish peroxidase was added to allow visualisation of the reaction. Polyclonal antibodies directed against either whole AHSV or viral core particles were suitable as detecting antibodies. On the other hand, a monoclonal antibody that was specific for a major core protein, VP7, gave a much weaker signal in the ELISA. All known AHSV serotypes were recognised in the F(ab')2-ELISA by polyclonal antisera against either whole virus particles or viral cores. Immunoprecipitation of AHSV structural polypeptides showed that such antisera contained populations of antibodies directed against core proteins. The F(ab')2-ELISA has potential as a diagnostic technique for AHSV infections. PMID- 2266147 TI - Antigen-capture ELISA for viral haemorrhagic septicaemia virus serotype I. AB - An antigen-capture ELISA for viral haemorrhagic septicaemia virus serotype I (VHSV I) was developed. The assay employs two monoclonal antibodies (mAb) directed against distinct epitopes of the viral envelope glycoprotein (Gp). The antigen bound by the capture mAb (A17) was detected by addition of a second mAb (L7) conjugated to horseradish peroxidase, followed by addition of the enzyme substrate. The technique is highly sensitive, enabling detection of the virus at a protein concentration as low as 1 ng/ml of total proteins (1.5 fmol of envelope Gp per ml) in purified preparations. VHSV I was also detected in culture supernatants (5 x 10(5) PFU/ml) and in extracts of kidney and spleen of rainbow trout infected experimentally (5 x 10(5) PFU/ml). The assay was highly specific: infectious haematopoietic necrosis virus, infectious pancreatic necrosis virus, spring viraemia of carp virus, pike fry rhabdovirus, eel rhabdovirus and perch rhabdovirus could not be detected by the antigen-capture ELISA for VHSV I. PMID- 2266148 TI - Variability in radioimmunoprecipitation assays of HIV. PMID- 2266150 TI - Lymphotoxin production by regional lymph node lymphocytes in patients with uterine cervical cancer. AB - The cytotoxin production by regional lymph node cells was examined in 25 patients with uterine cervical cancer and 10 patients with uterine myoma. The patients in stage I had significantly increased spontaneous release of cytotoxins compared with that in stages II, III, and IV. The spontaneous release in stages III and IV was markedly reduced. There was no difference in the release of cytotoxins from peripheral blood lymphocytes between cancer patients and patients with myoma or healthy controls. The cytotoxin production by lymph node cells was increased in stage III by stimulating with formalin-fixed QG-K cells derived from uterine cervical cancer, but not in stages I and II. Almost all of the cytotoxic activity of cytotoxin was abrogated by antilymphotoxin antibody. However, the cytotoxin activity was partially inhibited by anti-tumor necrosis factor antibody. These results suggest that cytotoxins released from the regional lymph node cells of uterine cancer patients are derived from, most of all, lymphotoxin. PMID- 2266149 TI - Pairing of VK and VK gene families in self-reactive antibodies. PMID- 2266151 TI - Polymerase chain reaction (PCR) amplification demonstrates the absence of human T cell lymphotrophic virus (HTLV)-I specific pol sequences in peripheral T-cell lymphomas. AB - HTLV-I seronegative patients in nonendemic areas have been described with T-cell proliferations the DNA of which contains specific HTLV-I viral sequences. We have looked for the presence of HTLV-I DNA sequences in 27 HTLV-I seronegative patients with peripheral T-cell lymphomas, distinct from adult T-cell leukemia (ATL), and four HTLV-I seropositive patients, three with an ATL and one with a tropical spastic paraparesis. Using HTLV-I pol specific primers, the genomic DNA from peripheral blood mononuclear cells and lymph nodes massively infiltrated by tumor cells was analyzed by the enzymatic gene amplification procedure. In contrast to the peripheral blood lymphocytes from the four HTLV-I seropositive patients, the peripheral T-cell lymphoma samples did not harbor HTLV-I pol sequences. The data show that the detection of HTLV-I nucleotide sequences by the polymerase chain reaction correlates with serologic analysis in this series. PMID- 2266152 TI - Pathophysiology of mild endometriosis: review of literature. AB - Endometriosis is a puzzling condition and the literature is characterized by a large number of uncontrolled reports on its aetiology and pathophysiology. In particular the relationship between mild endometriosis and subfecundity is uncertain. This paper critically reviews the published literature on the pathogenesis, prevalence, menstrual symptomatology and natural history of endometriosis. Furthermore, factors implicated in causing subfecundity in relation to endometriosis and the impact of various treatments in enhancing fertility among women with mild endometriosis have been assessed. PMID- 2266153 TI - A comparison of some clinical and endocrinological features between cycles with normal and defective luteal phases in women with unexplained infertility. AB - The luteal phase in a group of women (n = 49) with unexplained infertility was evaluated by improved methods, including the use of the LH surge for precise timing of measurements, quantitative techniques for histological dating of endometrial biopsy and determination of the integrated progesterone concentration in the luteal phase. Overall, 10 out of 49 (20%) women were considered to have a retarded endometrium. The prevalence of retarded endometrium in women with primary infertility (10/37, 27%) was found to be significantly higher (P less than 0.05) than in women with secondary infertility (0/12, 0%). Women with retarded endometrial development had a significantly (P less than 0.01) lower integrated P concentration than those with normal endometrial development; however, of the 10 cases with retarded endometrium, only four were associated with an integrated P concentration below the normal range, whereas the remaining six were associated with an integrated P concentration within the normal reference range, suggesting that an abnormal response of the endometrium is a likely cause of abnormality in these latter cases. There was no difference in age, duration of infertility, follicular phase length, magnitude of the oestrogen surge, magnitude of the LH surge, maximum follicular diameter and luteal phase length between women with a normal or defective luteal phase, defined either by endometrial morphology or integrated progesterone concentration. PMID- 2266154 TI - The treatment of patients with polycystic ovarian syndrome by in-vitro fertilization and embryo transfer: a comparison of results with those of patients with tubal infertility. AB - Sixteen patients with polycystic ovarian syndrome (PCO) were treated by in-vitro fertilization (26 treatment cycles). The results were compared with 37 normo ovulatory women with tubal disease (37 treatment cycles). The oestradiol and progesterone levels were higher during the follicular phase in the PCO patients, but were statistically significantly higher only on the day after human chorionic gonadotrophin administration. Although more oocytes were recovered per cycle from the PCO group (19.3 +/- 6.1) than from the control group (5.4 +/- 2.9) with P less than 0.004, the mean numbers of embryos per cycle were similar in both groups (3.7 +/- 2.4 versus 3.6 +/- 2.2, respectively). The pregnancy rate was also comparable in both groups (30.7 versus 29.7%, respectively). The fact that more oocytes are recovered from PCO patients, balances their lower fertilization and cleavage rates. We conclude, therefore, that IVF treatment may be a viable solution for PCO patients resistant to an in-vivo protocol treatment regimes. PMID- 2266155 TI - Trophectoderm biopsy in human blastocysts. AB - Trophectoderm biopsy was carried out on 47 human blastocysts. A slit was made in the zona pellucida opposite the inner cell mass by micromanipulative techniques. The human blastocyst zona offered more resistance to slitting compared to that of the mouse. After 18-24 h, controlled herniation of the trophectoderm cells was observed. These cells were biopsied when the diameter of the herniation was approximately equal to that of the blastocyst. The size of the slit and the stage of embryonic development at which slitting was performed were important for successful herniation to occur. After slitting, 76% of day 5-6 blastocysts showed herniation whilst only 42% of day 7-8 blastocysts herniated. Further development of the manipulated embryos was not apparently impaired, as hatching occurred in 44% of the former and 20% of the latter, compared with 18.1% in non-manipulated controls. The biopsied cells (approximately 10-30) usually remained in a clump but 14% formed vesicles on the day after biopsy. There was, however, no evidence of adherence to the dish or formation of monolayers. These results demonstrate the feasibility of trophectoderm biopsy in human blastocysts and that sufficient extra-embryonic material can be obtained by this technique for preimplantation diagnosis of genetic disorders. PMID- 2266156 TI - Analysis of the first polar body: preconception genetic diagnosis. AB - In women who are heterozygous for a genetic disease, genetic analysis of the first polar body allows the identification of oocytes that contain the maternal unaffected gene. These oocytes can be fertilized and transferred to the mother without risk of establishing a pregnancy with a genetically abnormal embryo. We have demonstrated that removal of the first polar body has no effect on subsequent fertilization rates or embryonic growth to the blastocyst stage. We have developed a PCR technique to successfully analyze the PI type Z and PI type M genotypes of alpha-1-antitrypsin deficiency and applied this technique for a couple at risk for PI type ZZ alpha-1-antitrypsin deficiency. After standard IVF treatment to stimulate multiple follicle development, eight oocytes were aspirated transvaginally. Polar bodies were removed by micromanipulation from seven oocytes and fertilization occurred in six cases. PCR analysis was successful in five oocytes. One was PI type M, two were PI type Z and two were heterozygous MZ due to crossing over. Embryos from the two oocytes containing the unaffected gene (polar body PI type Z) were transferred in the same cycle 48 h after insemination. No pregnancy was established. The accuracy of the polar body diagnosis was confirmed by polymerase chain reaction (PCR) analysis of an oocyte that failed to fertilize. PMID- 2266157 TI - Protein synthesis and acrosome reaction-inducing activity of human cumulus cells. AB - The acrosome reaction of human spermatozoa is a prerequisite to fertilization. It has been hypothesized that secretions of cumulus cells could be involved in the induction of this sperm reaction. A source of variation in the in-vitro fertilization of human oocytes could be the maturational differences in the cumulus cells which affect the acrosome reaction. In order to investigate this possibility, we have studied the capability of secretions obtained from cumulus cells of different maturational stages to induce the acrosome reaction. Capacitated spermatozoa were exposed to the culture medium containing cumulus cell secretions and their acrosomal status was evaluated using the triple stain technique. The maturational status of the cumulus or fertilization of the enclosed oocyte did not influence the percentage of acrosome-reacted live spermatozoa. In order to further document these observations, cumulus cells were submitted to [35S]methionine incorporation and total and secreted proteins were analysed by SDS-PAGE electrophoresis. Neither quantitative nor qualitative changes were detected in the electrophoretic patterns of the proteins obtained from cumulus cells of different maturational status. Thus, variation of the acrosome reaction-inducing activity of cumulus cells does not appear to be involved in the variable fertilization of oocytes obtained from follicles of differing maturity. PMID- 2266158 TI - A simplified approach to sperm-cervical mucus interaction testing using a hyaluronate migration test. AB - Fifty-one comparisons were made of human sperm migration into capillary tubes containing either human cervical mucus ('Kremer test') or a synthetic mucus substitute consisting of a 5 mg/ml solution of sodium hyaluronate (average mol. wt 2 x 10(6)) in a phosphate-buffered medium. The results of these two tests were highly significantly correlated and dependent upon the same sperm characteristics reflecting sperm progressive ability (including the specific movement characteristic of lateral head displacement amplitude), morphological normality and cellular vitality as well as the concentration of these more functional cells in the semen. The result of the hyaluronate migration test, in conjunction with the mucus quality measures of Insler score and pH, allowed a 92.2% correct prediction of the Kremer test outcome (90.9% of normal tests and 93.1% of abnormal tests). In this data set, these values also corresponded to the sensitivity and specificity of the analysis, respectively. From these studies, we propose the hyaluronate migration test as a useful adjunct to routine semen analysis, sperm movement analysis and the more traditional in-vitro tests of sperm-cervical mucus interaction in the diagnostic investigation of infertile couples. It effectively assesses the mucus-penetrating potential of a semen sample without the need for relatively large quantities of midcycle cervical mucus; it will therefore augment (as an internal control), although not necessarily replace, the homologous Kremer test and reduce the quantity of both patient and donor mucus needed for comprehensive crossed-hostility format testing of sperm-mucus interaction. PMID- 2266159 TI - Abnormalities of sperm chromosome condensation in the cytoplasm of immature human oocytes. AB - This study analysed data from 27 couples in an IVF-ET programme. The maternal age range was 28-43 years. Statistical analyses on 182 oocytes showed no maternal age effect on the number of oocytes, their stage of maturation or their fertilization rate. There was also no effect of age of either partner or of seminal parameters on the fertilization rate. In contrast, occurrence of diploid oocytes was confined to three of the older women. The proportion of failures of fertilization was significantly higher in immature oocytes. These failures, which included 18 uncleaved, multipronuclear or fragmented zygotes, were related to disturbances of oocyte maturation. Four (out of five) oocytes re-inseminated with fresh semen produced polyspermy. One zygote showed marked asynchrony in the development of the two pronuclei. In eight zygotes the paternal complements had an allocyclic pattern of chromosome condensation between and within chromosomes or chromosome regions. In two other zygotes the paternal complement showed one chromosome prematurely condensed. This single-chromatid chromosome would be lost in the following cleavage division, suggesting that aneuploidy due to 'anaphase lag' is not a rare event during embryo cleavage. PMID- 2266160 TI - Significance of cumulus oophorus in in-vitro fertilization and oocyte viability and fertility. AB - Fertilization and cleavage rates of human cumulus-intact oocytes incubated in vitro for 36-48 h with normal spermatozoa tended to be higher than those which were cumulus-denuded (73 versus 68%; 68 versus 56%, respectively); however, the difference was not significant. Nor were these differences significant when using sperm samples of various qualities (normozoospermic samples: 75 versus 70% fertilized oocytes; asthenozoospermic: 66 versus 64%; oligozoospermic: 64 versus 56%; oligoasthenozoospermic: 35 versus 33%). The beneficial effect of the human cumulus oophorus on the binding of human spermatozoa to denuded hamster oocytes and on head decondensation of human spermatozoa observed after 2 h of incubation (9.3 versus 7.0 bound spermatozoa per oocyte, P less than 0.05; 0.5 versus 0.3 decondensed sperm heads per oocyte, P less than 0.02) disappeared after 6 h. A protective effect of the cumulus oophorus on hamster oocytes preincubated in medium containing 50% human preovulatory follicular fluid was observed in the sperm penetration assay (fertilization rate of cumulus-intact: cumulus-denuded oocytes, 26 versus 13%, P less than 0.05) and confirmed using fluorescein diacetate stain (cumulus-intact oocytes: 86 versus 100% vitality, non significant; cumulus-denuded oocytes: 64 versus 100%, P less than 0.01). These data suggest the accelerating effect of the human cumulus oophorus on fertilization in its early stages. Furthermore, the cumulus plays an important part in protecting the oocyte against adverse environmental influences. PMID- 2266161 TI - Oocyte donation: the role of endometrial receptivity. AB - Sixteen patients, 15 with primary ovarian failure and one carrier of chromosomal abnormality, received 21 embryo transfers following in-vitro fertilization of donated oocytes. Hormone replacement therapy was given to mimic a natural menstrual cycle. Five pregnancies were achieved (four infants delivered and one early pregnancy loss). All patients had endometrial biopsies taken in a preceding cycle of hormone replacement therapy. The majority (61%) showed delayed maturation compared with the expected appearances for the day of the cycle as assessed on light microscopy. Patients who conceived had a significantly better endometrial response than those who did not. Five out of seven patients (71%) conceived when the endometrium was 'in phase' (less than 2 days' delay). This suggests that endometrial receptivity is a key factor in conception. The implications for improving outcome from in-vitro fertilization treatment are discussed. PMID- 2266162 TI - The use of mifepristone prior to prostaglandin-induced mid-trimester abortion. AB - It has previously been established that the administration of mifepristone prior to prostaglandin-induced second trimester termination of pregnancy significantly reduces the induction to abortion interval. In this study, mifepristone (600 mg) was administered 24, 36 and 48 h prior to extra-amniotic infusion of prostaglandin in an attempt to elucidate the optimal time interval. There was a significant reduction in the induction to abortion interval, dose of prostaglandin required and attendant side effects in all three treated groups compared to controls. However, there was no significant difference among the treatment groups, despite evidence of increased uterine activity 36 h following mifepristone administration. No bleeding was observed prior to prostaglandin infusion in any of the groups and it is suggested that mifepristone could be administered safely prior to hospital admission for termination. PMID- 2266163 TI - A survey of public attitudes toward oocyte donation between sisters. AB - Oocyte donation offers the possibility of pregnancy for many patients with premature ovarian failure (POF) and recently a number of patients have been requesting egg donation by a sister. While patients anxious to achieve a pregnancy are favourably disposed toward egg donation, the existence of favourable attitudes in others, and thus the amount of social support such patients will receive, depends upon the wider social environment. A survey of public opinion was conducted utilizing a random sample of 501 adults in Orange County, CA in an attempt to identify demographic correlates of attitudes. Log linear analysis demonstrated no relationship between attitudes and an array of demographic data (income, political party, age), but showed a significant relationship between sex of the respondent and attitudes towards egg donation. While more than half of respondents of both sexes were favourably disposed towards egg donation, men exhibited significantly (P = 0.005) more positive attitudes towards oocyte donation by a sister than did women. Women in the general population showed markedly less support for egg donation by a sister than POF patients have been demonstrated to show. The theory is proposed that female respondents are more wary of the symbolic meaning of the reproductive connection between a sister-in-law and a husband, while the POF patient's attitude is shaped in part by her desire for a pregnancy. The results have implications for the attitudes POF couples may face in the social environment and for the type of social support which may be recommended. PMID- 2266164 TI - Tension and stiffness of frog muscle fibres at full filament overlap. AB - Stiffness measurements in activated skeletal muscle fibres are often used as one means of estimating the number of attached crossbridges on the assumption that myofilament compliances do not contribute significantly to the fibre compliance. This assumption was tested by studying the effects of sarcomere length on fibre stiffness in the plateau region of the length-tension diagram (from 1.96 to 2.16 microns sarcomere length in the tibialis anterior muscle of the frog). Lengthening of the sarcomere across this region in fact, produces only an increase in the proportion of actin filament free from cross-bridges without altering the amount of effective overlap; no change in fibre stiffness is therefore expected if actin filaments are perfectly rigid. The results show that while tetanic tension remained constant within 1.5%, as the sarcomere length was increased from 1.96 to 2.16 microns fibre stiffness decreased by about 4%, indicating that a significant proportion of sarcomere compliance is localized in the actin filaments. A simple model based on the sliding filament theory was used in order to calculate the relative contribution of actin filaments to fibre compliance. In the model it was assumed that fibre compliance resulted from the combination of crossbridge compliance (distributed over the overlap zone) in series with thin filament and tendon compliances. The calculations show that the experimental data could be adequately predicted only assuming that about 19% of sarcomere compliance is due to actin filament compliance. PMID- 2266165 TI - Expression of human beta-myosin heavy chain fragments in Escherichia coli; localization of actin interfaces on cardiac myosin. AB - A cDNA clone coding for an internal fragment of slow-cardiac beta-myosin heavy chain was isolated from a lambda gt10 human skeletal muscle library. Six overlapping cDNA subclones, which span myosin heavy chain subregions and presumably interact with actin, were derived from this clone, fused to a beta galactosidase vector and expressed in Escherichia coli. Three of the subclones were obtained by PCR (polymerase chain reaction) which enables gene or cDNA fragments to be amplified independently of preexisting restriction sites. Initially, various experiments were carried out using a long MHC (myosin heavy chain) fusion protein containing the 50 kDa-20 kDa connecting region, the whole 20 kDa region and the short subfragment 2 region. This MHC fusion protein was chemically or proteolytically cleaved in the same conditions as the native myosin molecule. Whole and truncated forms of the MHC fusion protein were separated on polyacrylamide gels, electroblotted on nitrocellulose sheets and renatured. They were then assayed in overlay experiments with F-actin and/or myosin light chains in solution. Specific antibodies were used to detect interactions between heavy chain fragments and F-actin or light chains. We thus observed that one long heavy chain fragment synthesized by E. coli behaved like proteolytic or chemical MHC preparations made from native myosin molecules. Two chymotryptic fragments of the MHC fusion protein, which are soluble at low ionic strength, cosedimented with F actin in solution. Our results demonstrate that, in actin overlay experiments with whole fusion proteins, interactions seem to be due to the heavy chain fragment, not to the bacterial component. All interactions were non ATP sensitive. We further investigated the possible participation of the six recombinant MHC fragments in contributing to the actomyosin interfaces on the 50 kDa-20 kDa regions of the human cardiac beta-MHC. The present procedure, which enables the synthesis of any MHC fragment independent of any protease site, is a powerful new tool for studying structure-function relationships within the myosin molecule family. PMID- 2266166 TI - Effect of ionic strength on crossbridge kinetics as studied by sinusoidal analysis, ATP hydrolysis rate and X-ray diffraction techniques in chemically skinned rabbit psoas fibres. AB - In order to identify which steps in the crossbridge are affected by changes in ionic strength, we studied the effect of ionic strength on the rate constants and magnitudes of three exponential processes, the ATP hydrolysis rate and isometric tension during maximal activation (pCa 4.52, 5 mM MgATP). Equatorial X-ray diffraction measurements were also carried out in both relaxing and rigor conditions to examine whether the distance between thick and thin filaments changes with ionic strength (range: 100-300 mM). All experiments were carried out at 20 degrees C and at pH 7.0 on chemically skinned rabbit psoas muscle fibres. Isometric tension and muscle stiffness declined significantly as the ionic strength was increased from 150 mM to 300 mM. The concomitant decrease in the ATP hydrolysis rate was much less than tension, resulting in a large increase in the tension cost. Three rate constants of exponential processes, deduced from sinusoidal analysis, did not change appreciably. The magnitude parameters of all three processes diminished as the ionic strength was increased. During relaxation the filament spacing increased by 5% when the ionic strength was increased from 150 mM to 300 mM. After rigor induction, the spacing did not change with ionic strength. We conclude that a change in ionic strength modifies the rapid equilibrium between the detached state and the 'weakly attached' state, and that this causes considerable effect on isometric tension. We also conclude that other steps in the crossbridge cycle are less sensitive to ionic strength, and that the lattice spacing change is unable to account for the considerable effect of ionic strength on isometric tension. PMID- 2266167 TI - Three-dimensional structure of frozen-hydrated paracrystals of myosin rod. AB - Myosin rod, the tail fragment of myosin, aggregates into various structures at physiological ionic strength. One form, the type II paracrystal, a thin, ribbon like species, has recently been studied using conventional electron microscopy and was shown to possess two-dimensional order and, further, is likely to be useful in the investigation of the arrangement of myosin molecules in the backbone of the vertebrate muscle thick filament (Ward & Bennett, 1989). We have now examined this aggregate in the frozen-hydrated state by cryo-electron microscopy. Image analysis indicated that the projected structure has the same p12, plane group symmetry as seen after negative staining. A three-dimensional map, calculated from projections, indicated that the structure comprises a bilayer arrangement of strands of grouped rod molecules, with the strands parallel in each layer. The layers themselves are related by screw symmetry. Strands in adjacent layers have opposing polarity with their long axes at an angle of 32 degree to each other. Protein density measurements, carried out on unstained specimens using electron energy-loss spectroscopy, showed that the 44 X 13 X 13 nm unit cell is composed of 40% protein. The density measurements indicated that 9-12 rod molecules pass through each strand. Modelling rod molecules with 43 nm parallel overlaps in a body-centered tetragonal lattice produced a strand that compared favorably with the reconstructed strand. The size and content of these strands suggests that they are analogous to subfilaments observed in the vertebrate myosin thick filament. PMID- 2266168 TI - Assembly of connectin (titin) in relation to myosin and alpha-actinin in cultured cardiac myocytes. AB - By using polyclonal and monoclonal antibodies against connectin (titin) which stain the A-I junctional area and the A-band domain (polyclonal anti-connectin and monoclonal 4C9) and the I-band domain (monoclonal SM1), the developmental relationship of this elastic protein with sarcomeric proteins, especially and alpha-actin, was examined in embryonic chick cardiac myocytes in vitro under fluorescence microscopy. During premyofibril stages, I-Z-I proteins were detected first (alpha-actinin dots and diffuse actin [phalloidin and anti-troponin C] staining), and later in these areas connectin and myosin dots appeared with nearly identical distribution. Somewhat later, phalloidin-positive nonstriated fibrils were observed in a straight course. They were always reactive with antibodies against alpha-actinin and troponin C, but unreactive or only weakly reactive with anticonnectin and anti-myosin. Initially, alpha-actinin dots were aligned along these fibrils but did not form striations. As they aggregated to form Z-bands, connectin and myosin started to exhibit typical striation ('doublets' and A-bands, respectively). No difference in the staining pattern was observed with two kinds of monoclonal antibodies against different domains of connectin filaments (4C9 and SM1) at early phases. As myosin staining began to show clear A-bands, connectin epitopes became arranged in polarized positions. We conclude that primitive I-Z-I complexes appear prior to the assembly of connectin and myosin filaments and then connectin filaments, developing intimately and coordinately with myosin, become associated with the alpha-actinin lines. Thus it appears that the putative elastic protein connectin plays some role in integrating myosin filaments with the preexisting I-Z-I brushes. The occasional absence of connectin and A-bands between two Z-bands, beyond both of which clear sarcomeres have been formed, indicates that connectin is not a preformed scaffold of myofibrils on which sarcomeric proteins accumulate. PMID- 2266169 TI - Immunoelectron microscopic observations on tropomyosin localization in striated muscle. AB - Tropomyosin localization in striated muscle was studied by means of immunoelectron microscopy. Polyclonal and monoclonal antibodies to tropomyosin were allowed to diffuse into mechanically skinned single fibres dissected from frog semitendinosus muscle. Antibodies produced transverse I-band stripes with the expected periodicity of 38 nm. However, some differences were revealed among the various antibodies. While polyclonal antibodies generally showed 23 stripes, monoclonal antibodies showed an extra 24th stripe immediately adjacent to the Z line, implying some structural/functional uniqueness of this terminal tropomyosin. Furthermore, the stripes did not always lie parallel to the Z-line. When the Z-line was straight or slightly skewed, the stripes generally were parallel to it. However, when Z-line skew was more severe, the stripes remained perpendicular to the fibre axis, indifferent to the Z-line skew. This may implay that the coupling of tropomyosin to the thin filament is not tight. Finally, the monoclonal antibodies themselves exerted an anomalous effect on the Z-line, apparently extracting or shifting some of its mass. PMID- 2266170 TI - Mechanical properties of mammalian single smooth muscle cells. III. Passive properties of pig detrusor and human a terme uterus cells. AB - Cells isolated from pig urinary bladders and pregnant full term human uteruses were attached longitudinally between a microforce transducer and a length displacement apparatus. Cells were stretched by applying a series of ramp-like length changes of 0.2 s duration and 10.0 microns amplitude at intervals of 15 min. Passive forces upon straining were as high as 70-100 microNs. Following these peak forces stress relaxation occurred, levelling off approximately 50% of the maximum peak force. The maximum elastic modulus estimated for single cells was found to be at least a tenfold higher than was previously estimated from intact bladder strips. The relation between the increase in length and the increase in initial force increment was found to be approximately linear. An exponential equation was fitted to a selected number of stress relaxation curves. Relaxation curves of bladder cells show a clearly different time course as compared to bladder tissue strips, suggesting that a significant amount of relaxation in strips has to be contributed to the connective tissue components or to structural changes in these strips. PMID- 2266171 TI - Type II oestrogen binding sites in human colorectal carcinoma. AB - Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. PMID- 2266172 TI - Primary lymphoma of the liver: clinical and pathological features of 10 patients. AB - Nine out of 10 patients with primary lymphoma of the liver presented in a manner that did not suggest a tumour. The initial diagnoses were chronic active hepatitis in three cases and "granulomatous cholangitis", inflammatory pseudotumour, and anaplastic carcinoma in one case each. Moreover, extensive haemorrhagic necrosis in three cases initially suggested the Budd-Chiari syndrome. All the tumours were diffuse non-Hodgkin's lymphomas like the 50 cases reported previously, but they differed from most of these in that nine were of T cell phenotype. Five were pleomorphic small T cell, two T zone, and two T lymphoblastic lymphomas: only one was centrocytic and of B cell lineage. This report extends the range of clinical manifestations (diffuse hepatomegaly without a tumour), histological appearances (resemblance to chronic inflammatory or vascular liver diseases) and phenotype (of T cell lineage) of primary lymphoma of the liver: these features seemed to be related in this series. Recognition is important as prognosis remains favourable in appropriately treated cases. Although the appearances of the liver biopsy specimens may be difficult to interpret, the destructiveness of the infiltrate is an important clue to the diagnosis. PMID- 2266173 TI - Abnormal fucosylation of ileal mucus in cystic fibrosis: I. A histochemical study using peroxidase labelled lectins. AB - Peroxidase conjugated lectins were used to analyse the glycoproteins of small intestinal mucins in normal infants and those with cystic fibrosis to ascertain whether there are any detectable histochemical differences in saccharide composition. A significant decrease in Lotus tetragonolobus (LTG) binding fucose was shown in normal small intestinal mucin starting around 36 weeks' gestation with total absence of staining at term and beyond. In contrast, the age matched patients with cystic fibrosis showed persistent and intense LTG binding of fucose. These results provide the first clear histochemical evidence that cystic fibrosis mucin is abnormal and confirm the findings of previous biochemical studies. PMID- 2266175 TI - Monoclonal antibody B72.3 in benign breast lesions. AB - It has been suggested that the monoclonal antibody B72.3 may be useful as a diagnostic tool in fine needle aspirates of breast masses because it recognises "tumour associated glycoprotein (TAG)-72". The antigen was sought in paraffin wax sections of 43 normal and benign breast biopsy specimens, using the avidin-biotin complex technique, to assess the extent of its presence in non-malignant tissue. Strong focal staining was seen in 21 (49%) cases. In 29 cases of fibrocystic change staining was present in 17 (59%). All areas of apocrine metaplasia were positive, as well as a few normal ducts and acini and occasional areas of adenosis. Focal positivity was present in five out of 12 foci of ductal epithelial hyperplasia and in three out of seven radial scars. Staining was absent in two areas of lobular hyperplasia, three areas of sclerosing adenosis, and in a focus of lactational change. Focal positivity was also seen in two out of five fibroadenomas and in two out of three intraduct papillomas. Five normal subareolar sections and a section of normal lactating breast were negative. It is concluded that B72.3 monoclonal antibody can show focal reactivity with a variety of normal and benign epithelial mammary structures, and it is doubtful that its use would be of any help in differentiating benign from malignant cells in fine needle aspirates. PMID- 2266174 TI - Abnormal fucosylation of-ileal mucus in cystic fibrosis: II. A histochemical study using monoclonal antibodies to fucosyl oligosaccharides. AB - Abnormal fucosylation of cystic fibrosis mucin was previously shown using peroxidase conjugated lectins on ileal tissue sections. These abnormally fucosylated glycoproteins were investigated further using monoclonal antibodies to fucosyl oligosaccharides based on type 1 and type 2 blood group precursor chains. The results of this study, using monoclonal antibodies to blood group glycoproteins in cystic fibrosis, were negative, yet abnormal fucosylation had been found using lectin histochemistry. Using monoclonal antibodies, lectins, and appropriate enzymes, such as glycosyl hydrolases, it should be possible to delineate further the abnormality found in glycoproteins in cystic fibrosis on appropriately fixed ileal sections, obtained from infants at term presenting with meconium ileus. PMID- 2266176 TI - Comparison of two preparatory techniques for urine cytology. AB - Two methods of preparation of urine for cytology were compared retrospectively. In method 1 cells in the urine were fixed after the preparation of the smear; in method 2 the cells were fixed before smear preparation. Urine cytology reports were correlated with subsequent histological analysis. The specificities of urine cytology using both methods were high (99%). The sensitivity using method 1 was 87%; using method 2 it was 65%. This difference was significant. The cell preparation technique therefore significantly changes the sensitivity of urine cytology. Cellular fixation after smear preparation is preferable to smear preparation after fixation. PMID- 2266177 TI - Primary hepatic vascular leiomyosarcoma of probable portal vein origin. PMID- 2266179 TI - Postoperative necrotising granulomata in the cervix and ovary. PMID- 2266178 TI - Peliosis hepatitis after liver transplantation. PMID- 2266180 TI - Traumatic aneurysm of the left common carotid artery. PMID- 2266181 TI - Cross-linked fibrin degradation products as a predictor of pulmonary embolism. PMID- 2266182 TI - Medical students' views on necropsies. AB - Second and third year medical students were invited to write down their comments about necropsies during a pilot study of a postal questionnaire on the subject. Their comments were analysed in detail on the following aspects: about how useful and necessary a procedure the necropsy is in medical practice and in education; their personal distaste for the procedure; whether attendance at a necropsy should remain a compulsory part of a medical education; staff attitudes; observance of relatives' wishes; and feelings about necropsies carried out on self or relatives. The data collated from the questionnaire showed that, although students regard the necropsy as useful in clinical practice, a single demonstration does not clarify what its uses are. For some, the necropsy represents disrespect to its subject, and few students seemed aware of the use of the necropsy as an instrument of quality control. It is concluded that the unpleasant aspects of a necropsy demonstration should be kept to a minimum to encourage attendance and promote a sense of its value, and that it might be useful to influence and modify students' opinions before they become entrenched, perhaps by giving a higher priority to training in discussing dying and death in the medical curricula. PMID- 2266183 TI - The negative coroner's necropsy: a personal approach and consideration of difficulties. PMID- 2266185 TI - Helicobacter pylori in dyspeptic patients in Kuwait. AB - Two hundred and four patients, mainly Arabs, attending for upper gastrointestinal endoscopy at the gastroenterology clinic in Mubarak Al-Kabeer Hospital, Kuwait, were examined for evidence of infection with Helicobacter pylori and associated inflammation. Biopsy specimens of antrum, body, and duodenum; gastric juice; and antral mucosal brushings were investigated by microbiological, cytological, and histopathological methods. Clinical conditions diagnosed at endoscopy included gastritis, gastric ulcer, duodenitis and duodenal ulcer, but half the patients had endoscopically normal gastric and duodenal mucosae. H pylori was detected by one or more of the procedures in at least one specimen from 197 (96.6%) of the patients. Histological and cytological analysis showed equal sensitivity, but bacteriological culture was less reliable. The proportion of positive cases was high, compared with other reported series, which may have been accounted for by the variety of diagnostic techniques used in this study, the selected population (all with gastrointestinal symptoms) or genetic or environmental predisposing factors peculiar to the sample population. PMID- 2266184 TI - Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation. AB - Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes. PMID- 2266186 TI - Labelling of cells of the mononuclear phagocyte system in routinely processed archival biopsy specimens with monoclonal antibody EBM/11. AB - When first reported, EBM/11 reacted with mononuclear phagocyte system cells only in fresh frozen sections, but it has been shown to have similar cellular specificity in routine formalin fixed, paraffin wax embedded tissue. This was achieved by limited proteolysis with protease XIV before immunocytochemical staining. In archival biopsy specimens EBM/11 produced granular cytoplasmic staining of alveolar macrophages, Kupffer cells, tingible body macrophages and sinus histiocytes, cells of splenic cords, cortical and medullary macrophages of thymus; blood monocytes, peritoneal and mesothelial macrophages; bone marrow mononuclear cells, megakaryocytes and osteoclasts; lamina propria macrophages in the gastrointestinal tract, and connective tissue cells (presumptive macrophages) of thyroid, gall bladder, skin, pancreas, ovary, myometrium, endometrium, cervix, kidney, prostate, placenta, myocardium and breast. Unlike other anti-macrophage antibodies, EBM/11 did not react with granulocytes, lymphocytes, plasma cells, platelets, endothelial and epithelial cells in paraffin wax sections. It did not label skin Langerhans' cells, microglial cells, and interdigitating reticulum cells (as in frozen sections). This study opens a new area for the specific identification by EBM/11 of mononuclear phagocyte system cells in archival biopsy specimens. It also raises the possibility that some monoclonal antibodies, believed to be reactive only in frozen sections, may react in archival tissue after limited proteolysis with an appropriate enzyme. PMID- 2266188 TI - Expression of the prodynorphin gene in the developing and adult cerebral cortex of the rat: an in situ hybridization study. AB - A population of cortical neurons contains the opioid peptide dynorphin; the laminar distribution of these neurons in the adult cerebral cortex and their patterns of development are not well known. We have utilized in situ hybridization techniques to localize prodynorphin mRNA-containing neurons. Rats aged from embryonic day (E) 15 through postnatal day (P) 90 were used. Prenatal animals did not show any labeling in the cerebral cortex. By P4, prodynorphin was expressed in a small number of cortical neurons for the first time. The autoradiographic signal was restricted to perikarya. In the frontoparietal cortex, labeled neurons first appeared in layer V and the upper part of layer VI. Subsequently, from P11 onward, the band expanded in an "inside-out" sequence to include layers IV through II. In the posterior cingulate cortex and in the insular and perirhinal cortices, prodinorphin mRNA containing-neurons were located preferentially in layer V. In all cortical areas analyzed, a progressive increase in the packing density of neurons expressing prodynorphin mRNA was observed until P14; it decreased slightly thereafter. PMID- 2266189 TI - Monoclonal antibody Cat-301 identifies Y-cells in the dorsal lateral geniculate nucleus of the cat. AB - In mammalian visual pathways, information is carried in parallel channels from the retina through the visual thalamus to visual cortex. The cat's visual pathway comprises at least three major channels that begin with the X, Y, and W ganglion cells in the retina. In the dorsal lateral geniculate nucleus (LGN) of the thalamus, neurons in the X, Y, and W channels receive input from their retinal counterparts and can be discriminated from one another on the basis of their anatomical and physiological properties. The search for molecular properties that might correlate with anatomically or physiologically defined classes of neuron has been a major area of research in recent years. Monoclonal antibody Cat-301 recognizes a neuronal surface-associated proteoglycan in many areas of the mammalian central nervous system. In the cat LGN Cat-301 immunoreactivity is restricted to a subset of neurons. We show here that the distribution, size, morphology, and cortical projection pattern of Cat-301-positive LGN neurons match those previously described for Y-cells. Taken together with our previous studies of the development of immunoreactivity and the sensitivity of Cat-301 staining to visual deprivation, these studies suggest that Cat-301 specifically recognizes Y cells in the cat LGN. These results indicate that neurons within a physiologically and anatomically defined cell class share a molecular property. They further suggest that differences in molecular traits may reflect, and possibly subserve, differences in anatomical and physiological characteristics. PMID- 2266187 TI - Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function. AB - The antigenic phenotype of human fetal osteoclasts was compared with that of human tissue macrophages and macrophage polykaryons in foreign body lesions using a large number of monoclonal antibodies directed against myeloid (granulocyte/mononuclear phagocyte) antigens. Osteoclasts expressed a restricted range of macrophage-associated antigens including CD13, CD15A, CD44, CD45, CD54, (ICAM-1), CD71 (transferrin receptor), and CD68. These antigens were also present on macrophages and macrophage polykaryons both of which also strongly expressed CD11a,b,c, CD18, (LFA family), CD14, CD31, CD36, CD37, CD39 and CD43 antigens. There was also weak and occasional expression of CD16 (FcRIII), CD25 (interleukin 2 receptor), CD32 (FcRII), CD35 (C3b receptor) and HLA-DR by macrophage polykaryons. The presence of some macrophage associated antigens on osteoclasts is consistent with their originating from cells of the mononuclear phagocyte system. The numerous differences in antigenic phenotype between osteoclasts and macrophage polykaryons, however, suggest that their pathways of development and differentiation are not identical. The differences discerned in antigenic phenotype should also permit distinction between these polykaryons (and possibly their mononuclear precursors) in normal and diseased tissues. PMID- 2266190 TI - Matching of receptive fields in the association projections from SI to SII of cats. AB - Anatomical and electrophysiological experiments were performed on cats to investigate the pattern of divergence and convergence in the association projections from the first (SI) to the second (SII) somatic sensory cortex and to ascertain whether diverging and converging fibre components from SI have receptive fields (RFs) matching those of target neurons in SII. In the first group of six cats, a single deposit of horseradish peroxidase (HRP) was iontophoretically placed (2-4 microA for 20 minutes) into an electrophysiologically identified site of the SII map: the digit (3 cats), forepaw (2 cats), and arm (1 cat) zones. The forelimb representation in ipsilateral SI was subsequently explored with microelectrodes and RFs from small clusters of neurons systematically mapped. Planar maps of this area were reconstructed with the aid of a computer from serial sections, to correlate on the tangential plane the topographical distribution of retrogradely labelled association neurons with the physiological map of the forelimb. Since diverging projections were observed from a zone of SI to multiple zones of SII, double labelling experiments were carried out in a second group of three cats, in which two retrograde fluorescent dyes (diamidino yellow and fast blue) were injected by pressure into two different sites of the SII map, to ascertain whether SI sends diverging projections by branching axons. HRP injections in SII retrogradely labelled a discrete number of association neurons in SI. Their distribution area was several tens of times wider than that covered by the injection site. This suggests that a remarkable amount of divergence and convergence exists in the association projections from SI to SII. Despite the substantial difference in the extent of the injected and labelled areas, RFs of afferent and target neurons corresponded closely. Injections covering a small region within a single digit zone of SII labelled neurons throughout the entire representation of the same digit in SI, while neurons labelled in somatotopically inappropriate zones were rare. RFs mapped from several sites of the labelled region in SI were individually smaller than the RF mapped from the injection site in SII, but the overall size of afferent RFs encompassed that of target neurons. Divergence and convergence in the SI projections to SII zones representing more proximal portions of the forelimb may be even greater since HRP injections in the forepaw and arm zones of SII labelled a number of neurons also in the digit zone of SI, providing the RFs mapped from the injection sites were sufficiently wide to include the digits.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266191 TI - Collateral sprouting of the central terminals of cutaneous primary afferent neurons in the rat spinal cord: pattern, morphology, and influence of targets. AB - The capacity of the central terminals of primary afferents to sprout into denervated areas of neonatal spinal cord and the morphology of any novel terminals has been investigated. In rats which had undergone sciatic nerve section on the day of birth, 12 of 18 physiologically characterized intact saphenous hair follicle afferents (HFAs) were labelled intra-axonally with horseradish peroxidase (HRP) were shown to sprout up to 2,000 microns into the deafferented sciatic terminal field. The morphology of these sprouts depended on which area of the sciatic nerve territory was invaded by the afferent sprouts. Six HFAs sprouted into areas normally innervated by glabrous skin afferents and the morphology of the collateral sprouts in this region resembled that of rapidly adapting (RA) afferents. The other six saphenous HFAs had sprouted into sciatic "hairy" skin areas and the morphology of these sprouts, although abnormal, was flame shaped. In rats whose sural, saphenous, and superficial peroneal nerves were cut at birth, 4 of 7 single HRP labelled RA afferents had central terminals that had sprouted into regions of cord normally devoted to "hairy" input. These showed clear signs of HFA morphology despite their peripheral receptive fields remaining in the glabrous skin. The results show collateral sprouting of single cutaneous sensory afferent axons into adjacent inappropriate central target regions following neonatal deafferentation. Such plasticity may provide some compensation following neonatal injury. The morphology of the sprouted terminals is appropriate to the new target area rather than to its functional class and is also independent of the peripheral receptive field location providing an example of central rather than peripheral control over afferent growth patterns. PMID- 2266192 TI - Time course of structural changes in regenerating electroreceptors of a weakly electric fish. AB - We examined the regenerating electroreceptors of the weakly electric fish Sternopygus by light and electron microscopy to search for possible structural correlates of known physiological changes that occur during regeneration (Zakon: J. Neurosci. 6(11):3297-3308, 1986) and to compare them with developing electroreceptors in larval fish (Vischer: Brain Behav. Evol. 33:223-236). Nine days after removal of a patch of cheek skin, new skin had filled the wound and undifferentiated precursor cell clusters were located in the epidermis just above the dermis. Nerve fibers were present near most, but not all, cell clusters. A few recognizable tuberous and ampullary precursor organs were seen at this time. Tuberous organs were composed of a group of large cells surrounded by smaller cells without a lumen and showed the beginning of a cellular plug. Ampullary organs appeared as a ball of cells with a small lumen opening into a nascent canal. Degenerating cells were found within organs, and sometimes entire organs degenerated. These were not innervated. By 2 weeks the large cells of the tuberous organ were developing into sensory cells, while the smaller cells were forming the capsule wall and the underlying basal cells. The characteristic tuberous organ canal filled with loosely packed epidermal cells was evident. The sensory cells of the ampullary organs were visible within the epithelial layer at the base of the lumen, and the large synaptic discs were beginning to form. The sensory cells and postsynaptic terminals contained numerous vesicles. The presynaptic vesicles, which appear in normal receptor cells, remained throughout regeneration and presumably underlie transmitter release. The postsynaptic vesicles appeared transiently in large numbers but declined to adult values by 4 weeks. We presume that these may serve a trophic role. By 3 weeks, organs generally appeared mature and began dividing into daughter organs. The formation of individual receptor organs during regeneration is similar to that observed in development. Receptor organs continued dividing until the appropriate number of organs per afferent was reached for the size of the fish. Although the organization of the receptors appeared generally normal, there were a few anomalies. Some afferents sent sprouts into the epidermis, and, as a result of such sprouting, some of these afferents innervated multiple organs over a greater distance than normal. This was first seen early in regeneration and persisted for as long as 5 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266193 TI - Development of two morphological types of retinopetal fibers in chick embryos, as shown by the diffusion along axons of a carbocyanine dye in the fixed retina. AB - Centrifugal fibers to the retinas of chick embryos and hatched chicks have been examined and traced following staining by diffusion along their axonal membranes of the carbocyanine dye DiI in fixed tissue. In the older embryos and hatched chicks, the report of Dogiel (Arch. Mikrosk. Anat. 44:622-648, 1895) has been confirmed that there are two very different morphological types of centrifugal fiber. The restricted type ends as a relatively thick fiber, lacking varicosities, that runs for a short distance in the most sclerad level of the inner plexiform layer before terminating in a pericellular nest overlying the flask-shaped body of a single amacrine cell. Thin filaments occasionally leave the pericellular net, apparently to terminate on adjacent cells. The widespread type also runs in the most sclerad level of the inner plexiform layer, but it is thin, varicose, and highly branched, and its terminal arbor may span more than 1 mm, remaining at the same level. Both types of terminal arbor issue from parent axons in the optic fiber layer of the retina. A single parent axon gives either a single terminal fiber of the restricted type or several terminals of the widespread type, but never a mixture of the two. It is argued that the restricted and widespread types originate respectively from the neurons of the contralateral isthmo-optic nucleus and from the "ectopic" neurons scattered outside the isthmo optic nucleus. In development, the centrifugal fibers reach the retina between E9 and E10 and initially run radially in the optic fiber layer, parallel to the retinofugal fibers but avoiding the dorsal retina. They dive into the inner plexiform layer at about E12. By E13, the terminal arbors are forming, and the widespread and restricted types can already be distinguished. The widespread type continues to increase its territory until about E18, and then appears to remain stable, whereas the restricted type attains its maximum ramification between E13 and E15 and then contracts. Prior to the retraction, the terminal territories of the restricted type fibers overlap, which may provide the anatomical basis for the interaxonal competition that apparently contributes to neuronal death in the isthmo-optic nucleus between E13 and E16. Axons of ganglion cells exhibit transient side branches between E11 and E13; these never reach as deep as the level where the centrifugal fibers run. PMID- 2266194 TI - Times of origin of brachial sensory neurons are not correlated with neuronal phenotype. AB - The times of origin (birthdays) of sensory and motor neurons that innervate the triceps brachii muscles of the bullfrog (Rana catesbeiana) were determined to learn whether neurons innervating a specific target are generated at a particular developmental time. 3H-thymidine (3H-TdR) was made available continuously throughout a specific developmental period. All neurons that innervated the triceps muscle in juvenile frogs (identified by filling cells retrogradely with HRP) were generated prior to metamorphosis. Triceps motoneurons were all postmitotic by early limb bud stage V. Triceps sensory neurons were generated over a protracted period of larval development, from stage V through early pre metamorphic stage XV. Most large triceps sensory neurons were generated before the majority of the small cells. However, there was considerable overlap in the times of origin of the two populations; both large and small cells were generated at all stages of sensory neurogenesis. There was thus no strict relationship between sensory soma size and birthdate. Late-generated sensory neurons tended to be located in clusters within ganglia, whereas HRP-filled triceps neurons were not. These 3H-labeled clusters may represent clones of neurons which would indicate that late stage neuroblasts give rise to neurons that supply different peripheral targets. The time course of triceps neuronal generation paralleled that of all other brachial sensory neurons implying that the time of last cell division does not in itself determine either the target a neuron will innervate or the sensory modality to which it will respond. PMID- 2266195 TI - Synaptic connections of neuropeptide Y (NPY) immunoreactive neurons in the hilar area of the rat hippocampus. AB - Synaptic connections and fine structural characteristics of neuropeptide Y immunoreactive (NPY-i) neurons in the fascia dentata were studied using an antiserum against NPY. Normal and colchicine pretreated rats were examined to study the synaptic connections of NPY-i neurons in the normal fascia dentata. The perforant pathway and fimbria fornix were transected to label afferent fibers to NPY-positive cells. Horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA) was injected into the contralateral hippocampus to study commissural projections of hippocampal NPY-i neurons, and to search for NPY-i synaptic contacts on immunonegative commissural cells. Since earlier reports have shown that at least half of the NPY-i neurons also contain somatostatin (SS), the distribution of NPY-i neurons in the hilar area was determined and compared with that of SS-i neurons. Four types of dentate NPY-i neurons were distinguished: Type 1: large multipolar cells in the deep hilus (9%). Type 2: medium-sized multipolar and fusiform hilar neurons with dendrites occasionally reaching the outer molecular layer (64%). Type 3: pyramidal shaped cells in the granule cell layer with long apical dendrites reaching the outer molecular layer (20%). Type 4: small multipolar NPY-i cells located in the molecular layer (7%). Our results indicate two overlapping but not identical cell populations of NPY-i and SS-i neurons. Light and electron microscopic analysis of the normal fascia dentata demonstrated that the majority of NPY-i terminals are located in the outer molecular layer of the dentate gyrus, where they establish symmetric synaptic contacts on dendritic shafts and occasionally on spines of granule cells. A moderate number of NPY-i synapses were also found on dendrites in the inner molecular layer and on the cell body of granule cells. Numerous symmetric NPY-i synapses were found on dendrites and somata of neurons in the hilar area. Some NPY-i dendrites in the hilar area received mossy axon collateral input. After transection of the perforant pathway degenerated axon terminals could be found in synaptic contact with NPY-i dendrites in the outer molecular layer. Commissurotomy revealed direct commissural input to NPY-i dendrites in the inner molecular layer and in the hilus. After injection of HRP-WGA into the contralateral hippocampus 2% of hilar NPY-i neurons were retrogradely labeled and symmetric NPY-i synapses were found on the cell bodies and dendrites of unstained HRP-WGA labeled neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266196 TI - Milk yield and mammary function in goats during and after once-daily milking. AB - Starting in week 5 of lactation, goats were milked unilaterally once daily for 4 1/2 weeks, then twice daily for 12 weeks and finally thrice daily for 2 weeks. The control gland was milked twice daily throughout. During less frequent milking, yield fell by 26%. There was a rapid and essentially complete recovery of milk yield on resumption of twice-daily milking, and five of the six goats subsequently responded to thrice-daily milking with a small increase in milk yield. Mammary function was assessed during each phase by determining enzyme activities and in vitro synthesis rates of lactose and casein in mammary biopsies. There was a trend towards reduced differentiation of secretory cells during infrequent milking, with very little recovery during twice-daily milking but complete recovery during thrice-daily milking. The differentiative state of the control gland remained unchanged throughout. PMID- 2266197 TI - Yield and composition of milk from lactating mares: effect of lactation stage and individual differences. AB - The yields and composition of milk from nursing mares were studied during the first two months of lactation in 11 mares of heavy breeds (784 kg). Daily yield increased from 21.7 to 24.6 kg between weeks 1 and 8 of lactation. Fat, protein, gross energy and Ca concentrations significantly decreased when lactose content increased during this period. Individual variations were higher for yield than for composition. Casein, whey protein and non-protein N (56, 34 and 10% of crude protein, respectively) and amino acid composition did not vary between weeks 1 and 8 of lactation. PMID- 2266198 TI - The effects of intraruminal infusions of urea on the voluntary intake and milk production of cows receiving grass silage diets. AB - Responses of dairy cows given silage diets to the intraruminal infusion of urea in progressively increasing doses were studied in four experiments, two with non lactating cows and two with lactating cows. No clinical symptoms of NH3 toxicity were observed in any of the experiments. When urea was infused continuously, silage intake was depressed (P less than 0.05) when the total supply of N exceeded the equivalent of 250 g crude protein (CP)/kg DM in the total diet. However, when the urea load was administered twice daily, as opposed to continuously, intake depression (P less than 0.05) occurred at the equivalent of 170 g CP/kg DM. At the higher doses of urea, concentrations of NH3 in peripheral blood increased and were accompanied by increased concentrations of glucose and reduced levels of insulin in plasma. In general, responses of milk production followed those of silage intake but there was evidence of greater proportional reductions in the yield of lactose relative to that of fat and protein. It is concluded that the voluntary intake of high-protein silages may be depressed by factors associated with high rates of absorption of NH3 from the rumen. PMID- 2266199 TI - Effect of plane of nutrition on insulin sensitivity during lactation in the ewe. AB - The hyperinsulinaemic euglycaemic insulin clamp technique was used to compare insulin sensitivity in lactating ewes at two levels of feeding. Clamps were performed at two (restricted intake) or three (ad libitum intake) stages of lactation and also 30 d after drying off. Dose response curves for insulin were constructed using the glucose metabolic clearance rate (MCR) as the measure of glucose metabolism and these were statistically compared between stages of lactation within the feeding levels, and also between feeding regimes. Animals on a restricted feed intake showed a weight loss throughout lactation, coupled with a lower insulin sensitivity as measured by the ED50 (concentration of insulin required to produce a half maximal increase in MCR), while those on ad libitum feeding showed a weight gain and a decreased insulin sensitivity in the dry period. Endogenous glucose production was less sensitive to inhibition by insulin in the animals subjected to restricted food intake, compared with those on the ad libitum regime, which suggested a major role for the plane of nutrition in adjusting the homeorhetic control of metabolism during lactation. PMID- 2266200 TI - Effects of dehydration and arginine vasopressin infusions on the production of milk and the morphology of the goat udder. AB - Lactating goats were subjected to dehydration and to infusions of arginine vasopressin (AVP). Dehydration decreased milk production significantly but no changes were observed on the day of AVP infusion. The levels of AVP in plasma reached the same magnitude during both experimental procedures. AVP immunoreactivity was immunocytochemically detected by light (peroxidase antiperoxidase technique) and electron microscopy (immuno-Au technique on to glutaraldehyde-fixed, resin-embedded sections) in the mammary gland but not in the control experiments. In addition the cisternae of the rough endoplasmic reticulum in the secretory alveolar cells underwent significant swelling in response to the experimental procedures. PMID- 2266201 TI - Local control of the onset of mammary extraction of plasma triglycerides during lactogenesis in the goat. AB - In five untreated goats, mammary extraction of plasma triglycerides increased at parturition. In five goats that had as much secretion as possible regularly removed from one mammary gland beginning on d 143 of gestation, the change of triglyceride extraction occurred several d before parturition in the emptied gland but at parturition in the contralateral control gland. The experimentally induced early increase of extraction of plasma triglycerides preceded the increase of prostaglandin F alpha concentration in mammary secretion at parturition, and occurred despite abnormally high concentrations of progesterone in the secretion. PMID- 2266202 TI - Measurement of machine-induced changes in thickness of the bovine teat. AB - Machine milking induced repeatable, short-term changes in thickness of the teat apex. These changes were measured with a spring-loaded caliper instrument under milking conditions that imposed differing forces on the teat apex. The mean percentage changes in teat end thickness (relative to the premilking values for individual teats) varied from 10% decrease up to 20% or more increase depending on the particular milking system used. The overall decrease in teat end thickness associated with cannula milking, milking at very low vacuum levels or milking with positive pressure pulsation may result from: (i) decrease in the intramammary pressure; and/or (ii) small changes in tone of teat musculature; and/or (iii) changes in the distribution of interstitial fluids in the teat apex. The overall increase in teat thickness caused by conventional or PKME milking systems results mainly from oedema (the extravascular accumulation of fluid). It is likely that milking equipment can, and should, be designed to minimize circulatory impairment resulting in oedema of the teat. PMID- 2266203 TI - Glycoproteins in the heat-and acid-stable fraction of ovine milk. AB - Affinity chromatography on a concanavalin A-Sepharose support was used to isolate two glycoprotein fractions from a heat- and acid-stable fraction of ovine milk. One of these glycoprotein fractions was purified by rechromatography on DEAE cellulose to essentially a pure protein yielding a single band on gel electrophoresis. The apparent Mr of this glycoprotein (GP2) as estimated by electrophoresis was 5,500. It contained 8.88% carbohydrate and 0.61% P. The other glycoprotein fraction (GP3) contained 0.53% P and 17.76% carbohydrate including sialic acid, mannose, galactose, fucose, galactosamine and glucosamine. It appeared on electrophoresis in acrylamide gels as a slow-moving broad band. On similar treatment in the presence of sodium dodecyl sulphate it revealed four glycoprotein zones with apparent Mr of 15,200, 18,300, 23,500 and 25,300. Both GP2 and GP3 contained low amounts of aromatic and sulphur-containing amino acid residues and large amounts of Asp, Glu, Ser and Leu. GP3 is similar in some respects to the bovine milk heat-and acid-stable fraction constituent, component 3. PMID- 2266204 TI - HPLC and GLC analysis of the triglyceride composition of bovine, ovine and caprine milk fat. AB - A total of 116 molecular species of triglycerides were identified in milk fat using a combination of HPLC and GLC. Triglyceride composition was predicted from the random composition, which was calculated on the basis of the mole fractions of the main fatty acids making up the total triglyceride fraction. The qualitative composition of the milk fat was similar in cows', ewes' and goats' milk. In all three milks the partition number of the main triglycerides was 46, but the proportions of the triglycerides with partition numbers of 34, 38, 42, and 48 exhibited substantial differences among the milks of the three species. PMID- 2266205 TI - Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia. AB - Oculomotor functioning of 26 probands with schizophrenia, 12 spectrum and 46 nonspectrum first-degree relatives, and 38 nonpsychiatric control subjects was evaluated. Spectrum relatives had more anticipatory saccades (ASs) and lower pursuit gain than nonspectrum relatives, who had more ASs and lower pursuit gain than control subjects. Probands also had lower pursuit gain than nonspectrum relatives and control subjects but did not differ from other groups on AS frequency. Control subjects had more globally accurate pursuit tracking (root mean square [RMS] error deviation) than both relative groups, whereas probands had the poorest RMS scores. Square wave jerk frequency did not differentiate the groups. Attention enhancement affected the frequency of ASs but did not affect either the other intrusive saccadic event or RMS scores. These results offer evidence that eye-movement dysfunction may serve as a biological marker for schizophrenia. PMID- 2266206 TI - Hypnotizability and automaticity: toward a parallel distributed processing model of hypnotic responding. AB - We tested a hypothesis from parallel distributed processing theory that highly hypnotizable subjects have greater connection strengths along verbal pathways and would show greater Stroop effects than low hypnotizable subjects. Using Cheesman & Merikle's (1986) paradigm, which varied cue visibility and probability, we assessed automatic and strategic effects on Stroop performance. Compared with 9 low and 9 moderately hypnotizable subjects, 9 highly hypnotizable ones showed significantly greater Stroop effects for both visible- and degraded-word trials. No strategic differences emerged for the 3 hypnotizability groups. These findings support the contention that highly hypnotizable persons have stronger verbal connection strengths than their moderately and low susceptible counterparts, and they may account for highly hypnotizable persons' propensity to disregard personal attributions and label their responses in hypnosis as being involuntary. PMID- 2266207 TI - Severity of psychosocial stress and outcome of alcoholism treatment. AB - We examined the relation between stressful life events and drinking outcome among 129 male alcoholics who had completed an alcohol treatment program. Life events were assessed for the year prior to treatment and for the 3 months after treatment and were rated on the Psychiatric Epidemiology Research Interview and the Contextual Rating System. Approximately 40% of the pretreatment stressors were found to be directly or indirectly related to alcohol use. When stressors related to drinking were excluded from consideration, we found that men who returned to drinking after treatment experienced more severe or highly threatening stress before their relapse than men who remained abstinent during the follow-up period. These data suggest that although less severe stress may not increase risk for relapse, acute severe stressors and highly threatening chronic difficulties may be associated with elevated relapse risk. PMID- 2266208 TI - Peer-group association and adolescent tobacco use. AB - Mosbach & Leventhal (1988) examined the relation of cigarette smoking to peer group identification in rural Wisconsin adolescents. They found that among dirts (problem-prone youth), regulars (average youth), hot-shots (good social or academic performers), and jocks (athletes), youth most likely to smoke were dirts and hot-shots. We performed a replication with a Southern California cohort and also for use of smokeless tobacco. We hypothesized that jocks would be the main users of smokeless tobacco. We identified the same groups and an additional one, skaters (skateboarders or surfers). As Mosbach & Leventhal found, cigarettes were used most by dirts. Contrary to their results, but consistent with other research, we found that hot-shots were least likely to smoke. Contrary to our prediction, we found that skaters and dirts were more likely to use smokeless tobacco than were jocks. Our data show that both tobacco forms are used by problem-prone youth. PMID- 2266210 TI - Interpersonal perceptions and consequences of depressive-significant other relationships: a naturalistic study of college roommates. AB - We investigated social perceptions and consequences of depression and anxiety in roommate relationships. Mildly depressed, anxious but nondepressed, and nondepressed-nonanxious students (targets) and normal, same-sex roommates (a) rated the interpersonal impact on themselves of typical associations with their roommates and (b) judged their own interpersonal impact. Only depressed men received negative evaluations and emotional reactions from their roommates. However, depressed women reported more negative reactions to their normal roommates than vice versa. Finally, depressed targets perceived their interpersonal impact negatively, whereas their normal roommates perceived their own interpersonal impact as overly positive. These findings suggest that negative relationships between depressives and nondepressed others may be attributable, at least in part, to both participants' misperceptions of their social behavior and its consequences. PMID- 2266209 TI - Perceptions of parental relationships in the eating disorders: the relevance of depressed mood. AB - Recent studies have suggested that subtypes of eating-disordered persons differ in their perceptions of their family environments. This study used Benjamin's (1983) Structural Analysis of Social Behavior to examine how depressed mood influenced eating-disordered subjects' ratings of their parental relationships. The results indicated that when level of mood disturbance was statistically controlled, there were no significant differences in parent ratings among restricting anorexics, bulimic-anorexics, bulimics, and normal control subjects. The results are discussed in terms of the possible relations of mood, eating disorder, and perception of family relationships. PMID- 2266211 TI - Performance of criminal psychopaths on selected neuropsychological tests. AB - Screening batteries of standard neuropsychological tests were administered to 2 different samples (Ns = 90 and 167) of male prison inmates. Scores on the revised Psychopathy Checklist were used to divide inmates in each sample into high, moderate, and low psychopathy groups. There were no group differences in test performance in either of the samples, even when the effects of self-reported psychopathology and substance abuse were taken into account. The overall prevalence of both test-specific and global neuropsychological impairment was low and did not vary significantly across the 3 groups. The results provide no support for traditional brain-damage explanations of psychopathy. PMID- 2266212 TI - Body weight and bulimia as discriminators of psychological characteristics among anorexic, bulimic, and obese women. AB - Bulimic women from underweight (n = 20), normal-weight (n = 31), and overweight (n = 22) categories were compared with restrictor anorexics (n = 20), normal controls (n = 31), and obese subjects (n = 22). Each subject was administered the Minnesota Multiphasic Personality Inventory, the Internal-External Locus of Control Scale, the Rosenberg Self-Esteem Scale, and the Semantic Differential Potency Scale. Bulimic women in all 3 weight categories exhibited greater psychopathology, more external locus of control, lower self-esteem, and lower sense of personal effectiveness than nonbulimic women at similar weight levels. The highest psychopathology, lowest self-esteem, and most external locus of control were found among the underweight bulimic women. Significant differences between bulimic women of different weight levels suggest the need for some modification of treatment approaches depending on the bulimic women's weight level. PMID- 2266213 TI - Hostile attributional biases in severely aggressive adolescents. AB - Adolescent boys (N = 128) from a maximum security prison for juvenile offenders were administered a task to assess hostile attributional biases. As hypothesized, these biases were positively correlated with undersocialized aggressive conduct disorder (as indicated by high scores on standardized scales and by psychiatric diagnoses), with reactive-aggressive behavior, and with the number of interpersonally violent crimes committed. Hostile attributional biases were found not to relate to nonviolent crimes or to socialized aggressive behavior disorder. These findings held even when race and estimates of intelligence and socioeconomic status were controlled. These findings suggest that within a population of juvenile offenders, attributional biases are implicated specifically in interpersonal reactive aggression that involves anger and not in socialized delinquency. PMID- 2266214 TI - Congruence of personality and life events in depression. AB - Consistent with the personality-event congruence hypothesis, highly sociotropic depressed patients (n = 19) reported more recent negative interpersonal events than negative autonomy events and more negative interpersonal events than did highly autonomous depressed patients (n = 22), for whom the hypothesis was not supported. There was no evidence of such congruence among nondepressed schizophrenic patients (n = 44). In a second study, there was significant personality-event congruence in dysphoric students (n = 26) but not in nondysphoric students (n = 56). Both the high-sociotropy and high-autonomy dysphoric groups separately yielded nonsignificant trends consistent with congruence. These findings add to the growing support for the importance of the sociotropy construct in depression and weaker support for the autonomy construct or its measurement, and they suggest that the congruence effect does not generalize to all psychopathologies. PMID- 2266216 TI - The enhancing effects of anxiety on arousal in sexually dysfunctional and functional women. AB - Effects of anxiety on sexual arousal were examined to determine if sexually dysfunctional and functional women exhibit different patterns of physiological and subjective response. Subjects viewed 2 videotape conditions: an anxiety evoking and neutral-control preexposure stimulus, each paired with a sexual arousal-evoking stimulus. Anxiety preexposure enhanced the rate and magnitude of genital arousal for both dysfunctional and functional subjects in relation to the neutral condition. Despite increased genital responses, both groups reported less subjective sexual arousal after anxiety preexposure. Functional subjects exhibited greater physiological but not subjective arousal than dysfunctional subjects in both conditions. Results are discussed in terms of desynchronous patterns of sexual response, mechanisms by which sympathetic activation enhances sexual arousal, and implications for treatment of sexual dysfunction in women. PMID- 2266215 TI - Selective processing of threat cues in posttraumatic stress disorder. AB - Vietnam combat veterans with (n = 15) and without (n = 15) posttraumatic stress disorder (PTSD) performed a modified Stroop task in which they named the colors of neutral words (e.g., INPUT), positive words (e.g., LOVE), obsessive-compulsive disorder (OCD) words (e.g., GERMS), and PTSD words (e.g., BODYBAGS). In contrast to normal controls, PTSD patients took significantly longer to color-name PTSD words than to color-name neutral, OCD, and positive words. Because Stroop interference reflects involuntary semantic activation, it may provide a quantitative measure of intrusive cognitive activity--the hallmark symptom of PTSD. PMID- 2266217 TI - Depressive personality: reliability, validity, and relation to dysthymia. AB - The reliability and validity of Schneider's (1958) construct of depressive personality was evaluated in a sample of 177 outpatients, who were administered structured diagnostic and family history interviews, an extensive battery of inventories, and a 6-month follow-up assessment. The criteria for depressive personality had moderate to good interrater reliability, internal consistency, and test-retest stability, and the assessment of depressive personality traits was not influenced by patients' clinical states. In addition, preliminary support for the convergent and discriminant validity of the depressive personality construct was obtained. Although there were significant relations between the depressive personality and Diagnostic and Statistical Manual of Mental Disorders (3rd ed. and rev. 3rd ed.; American Psychiatric Association, 1980, 1987) diagnoses of dysthymia, the depressive personality was not entirely subsumed by existing mood disorders. PMID- 2266218 TI - Relation of social and academic competence to depressive symptoms in childhood. AB - Relation of depressive symptoms to social and academic competence was examined in 750 4th-grade students. Self-report, peer-nomination, and teacher-rating measures of all three constructs were obtained. The multitrait-multimethod data were examined with confirmatory factor analysis and multivariate analysis of variance. Stronger correlations than have previously been reported were found between depressive symptoms and both kinds of competence. Social and academic incompetence had an additive effect on depressive symptoms. Children who were both socially and academically less competent had more symptoms of depression than children who had only one problem area. Children with only one problem area had more symptoms of depression than did children who were neither socially nor academically less competent. Gender differences in other-rated measures of competence were also evident. Implications for a competency-based model of depression are discussed. PMID- 2266219 TI - Alcohol and drug abuse-dependence disorders in psychopathic and nonpsychopathic criminal offenders. AB - Co-occurrence of psychopathy (assessed with the Psychopathy Checklist) and lifetime Diagnostic and Statistical Manual of Mental Disorders (3rd ed.) alcohol and drug disorders (assessed with the National Institute of Mental Health Diagnostic Interview Schedule) was examined in a sample of 360 male inmates. Consistent with previous research that used diagnoses of antisocial personality disorder, psychopaths were more likely than nonpsychopaths to have lifetime diagnoses of alcoholism, any drug disorder, and multiple drug disorders. We also examined the relation between substance abuse and the 2 factors of the Psychopathy Checklist. Substance abuse was significantly related to general social deviance (Factor 2) but was unrelated to core personality features of psychopathy (Factor 1). We present two possible models of psychopathy (unitary syndrome vs. dual-diathesis model) that may account for the association between psychopathy and substance abuse. PMID- 2266220 TI - The frequency and significance of additional self-reported psychiatric diagnoses in children with attention deficit disorder. AB - The frequency of additional self-reported diagnoses in a large, heterogeneous sample of attention deficit disorder (ADD) children (N = 182) was determined using the Diagnostic Interview for Children and Adolescents (DICA). Over half the children had additional DICA diagnoses, with oppositional disorder and anxiety/mood disorders the most frequent. ADD boys with internalizing-type diagnoses had lower verbal IQs and arithmetic scores and performed more poorly on attention tasks than those without; parents also rated them more adversely. Those with externalizing-type diagnoses were rated as more aggressive by teachers and had sociopathic, thrill-seeking profiles on paper-pencil self-ratings. Over 40% of the children were dyslexic or slow learners but they had no higher rate of DICA diagnoses than those who read adequately. PMID- 2266221 TI - Enhancing the effectiveness of self-administered videotape parent training for families with conduct-problem children. AB - Parents of 43 conduct-problem children, aged 3-8 years, were randomly assigned to one of two treatments: an individually self-administered video-tape modeling treatment (IVM) and IVM treatment plus therapist consultation (IVMC). Randomization also included a waiting-list control group (CON). Compared with the control group, both treatment groups of mothers reported significantly fewer child behavior problems, reduced stress levels, and less use of spanking. Home visit data indicated that both treatment groups exhibited significant behavioral changes. There were relatively few differences between the two treatment conditions. However, the IVMC children were significantly less deviant than the IVM children, suggesting that the IVMC (with therapist consultation) treatment was superior to self-administered treatment with no therapist involvement. The added benefits of therapist involvement are discussed. PMID- 2266222 TI - Are hyperactive children deficient in attentional capacity? AB - A dual task was used to study attentional capacity in three groups: in 6- to 12 year-old boys with attention deficit disorder plus hyperactivity (ADDH) or with ADDH and conduct disorder, and in normal children. Subjects performed a primary choice reaction-time task first without and then with a secondary task that also required a response. Our prediction that the reaction time of ADDH subjects to the secondary task would increase more with increasing temporal overlap of the primary and secondary stimuli, if they were deficient in capacity, was not supported. However, the performance of ADDH subjects on the primary task deteriorated more than that of control subjects with the introduction of the secondary task, indicating a greater concurrence cost or a different allocation policy. Moreover, ADDH subjects had longer reaction times to the secondary task, indicating greater refractory effects or difficulty shifting capacity from primary- to secondary-task processes. PMID- 2266223 TI - Disruptive behaviors in the classroom: initial standardization data on a new teacher rating scale. AB - This study presents initial standardization data on the Sutter-Eyberg Student Behavior Inventory (SESBI), a teacher-completed measure of disruptive classroom behaviors. SESBIs were completed on 1116 children in kingergarten through fifth grade in a rural eastern Washington school district. Various analyses (Cronbach's alpha, corrected item-total correlations, average interitem correlations, principal components analyses) indicated that the SESBI provides a homogeneous measure of disruptive behaviors. Support was also found for three factors within the scale (e.g., overt aggression, oppositional behavior, and attentional difficulties). While the child's age did not have a significant effect on the SESBI, the child's gender did have a significant effect on scale scores as well as on most of the items, with males being rated more problematic than females. The SESBI was also able to discriminate between children in treatment for behavioral problems or learning disabilities and children not in treatment. PMID- 2266224 TI - Perceived family environments of depressed and anxious children: child's and maternal figure's perspectives. AB - This study examined perceived environment among families with a depressed, depressed and anxious, anxious, or normal child from the 4th to 7th grades. Fifty one such children were classified according to criteria from the K-SADS and a set of self-ratings of depression and anxiety. Results showed that children in all three diagnostic groups, and to a lesser extent their mothers, experienced their families as more distressed on a host of dimensions relative to controls. In addition, significant differences were found between families with a depressed and anxious child and those with an anxious child. Discriminant function analyses revealed that 68.63% of the youngsters could be classified correctly into depressed and anxious groups on the basis of their family ratings alone. PMID- 2266225 TI - Executive processing differences between learning-disabled, mildly retarded, and normal achieving children. AB - This study examined possible executive processing differences between mildly retarded, learning-disabled, and normal achieving children. To this end, the groups were compared as to their ability to recall central and secondary words from base and elaborative sentences under conditions of high and low encoding effort. Executive processing was inferred from the children's ability to maintain optimal recall performance for central and secondary words. Groups were comparable in central recall, but differences in secondary recall occurred for the high-effort encoding condition. Qualitative differences related to the prioritizing of resources (as reflected in the correlation between central and secondary recall) and monitoring the transfer of information (as reflected from central and secondary recall insertions) were found between groups. The results were discussed in terms of an executive processing framework that views retarded children as suffering from inefficiencies related to the sharing of resources, whereas the learning-disabled children's inefficiencies were related to the discrimination of resources. PMID- 2266226 TI - Social problem-solving in depressed, conduct-disordered, and normal adolescents. AB - Although past theory and research implicate social problem-solving deficits in both depression and aggressive disorders, research examining carefully diagnosed groups of adolescent depressed and conduct-disordered groups had not previously been conducted. In the current study three groups of adolescents (major depression, conduct-disordered, and normal) were studied using two social problem solving measures. Both the Means-Ends Problem-Solving task (MEPS) and the Social Situations Analysis measure (SSA) failed to show social problem-solving problem deficits in the depressed group relative to their normal age peers, but did provide corroborative evidence for social problem-solving deficits in the conduct disordered sample. Relative to the other two groups, the conduct-disordered adolescents were found to generate fewer means to a social end, to anticipate fewer obstacles in the pursuit of solutions to interpersonal situations, and to generate fewer assertive behavioral solutions to difficult social situations. The results are discussed in relation to other work with depressed and aggressive youth, and directions for future research are given. PMID- 2266227 TI - The monitoring skills of troubled mothers: their problems in defining child deviance. AB - Thirty-three clinic-referred mother-child dyads were observed in their home settings and one of the home observations was videotaped. These pretreatment observations were analyzed to determine the degree to which mothers provided indiscriminate reactions to their children's prosocial/neutral and deviant responses. We suspected that these reaction tendencies were connected to maternal deficiencies in their monitoring of child behavior. To pursue this suspicion, monitoring performance was assessed by having the mothers watch their own videotaped home observations and, using their own definitions, code their children's positive and aversive responses. Professional observers then replicated this coding task. Results showed mothers and professionals to be in fair agreement in coding child positive responses, but in poor agreement coding the child aversive responses. Mothers tended to undercode these latter responses and to be highly inconsistent in their own coding. When measures of maternal coding bias were correlated with maternal indiscriminate child care reactions, the bias in coding child aversive responses proved to be associated, while the positive coding bias was not. Discussion of these findings was focused on maternal insensitivity as promoted by the mothers' conservative and ambiguous definitions of child deviance. PMID- 2266228 TI - Histamine blocks interleukin 2 (IL-2) gene expression and regulates IL-2 receptor expression. AB - Histamine inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to the T cell mitogen Phytohemagglutinin-P (PHA-P) in a dose-dependent fashion. This inhibition was mediated via the H2 receptor since cimetidine, a known H2 antagonist, removed the inhibition, whereas the addition of the H1 antagonist Diphenhydramine did not. Inhibition occurred during the inductive phase of the cell cycle, since histamine added 24 hours after PHA-P stimulation had no effect on subsequent T cell proliferation, and was attributable to inhibition of interleukin-2 (IL-2) gene expression. Both secreted IL-2 and messenger RNA coding for IL-2 were inhibited by histamine. In contrast, histamine exerted no inhibitory effect on the expression of cell surface receptors for IL-2 as determined by flow cytometry. Furthermore, histamine treated cells retained full responsiveness to exogenously administered IL-2, which completely reversed the anti-proliferative effect of histamine. In some donors, histamine enhanced the percentage of IL-2 receptor positive cells. Stimulated PBMC from AIDS KS patients as a group, displayed a lower percentage of IL-2 receptor bearing cells, which was significantly increased by the addition of histamine even at concentrations as low as 10(-6) M and peaking at 10(-3) M. These findings indicate that histamine exerts its anti-proliferative effects on T cells by inhibiting IL-2 production, via blockade of IL-2 gene expression. In addition, histamine seems to exert immunomodulating effects on IL-2 receptor expression, particularly in those individuals with AIDS-KS. PMID- 2266229 TI - Natural killer activity is present in rat lung lavage and inhibited by lidocaine. AB - Natural killer (NK) cells play an important role in defense against tumors and certain infected cells. Although NK activity is present in cells recovered from lung parenchyma, its demonstration in cells retrieved from normal bronchoalveolar lavage (lung lavage) has been difficult. In this study, we report that NK cells are present and active in normal rat lung lavage. Purified effector cells retrieved from lung lavage and peripheral blood mononuclear cells were compared for NK activity. NK activity was tested in a four hour 51-chromium release assay against radiolabeled Yac-1 target cells and expressed as lytic units (LU). There was no difference in NK activity between the blood and lung (80 +/- 10 LU vs. 62 +/- 15 LU). Since lidocaine is used in lung lavage for topical anaesthesia in humans and to increase the cell yield in animals, we also sought to determine if it could affect NK activity. We found that lidocaine inhibited NK activity in a dose dependent manner when it was instilled into the airways prior to performance of lavage. Lidocaine did not affect the yield of cells recovered from lavage, their relative proportions, nor their viability. Lung macrophages (93 +/- 1% nonspecific esterase positive) inhibited blood NK activity, an effect significantly augmented by lidocaine. In sum, we report that NK activity in lung lavage is similar to that found in blood and may be regulated by alveolar macrophages and that topical lidocaine inhibits NK activity, an effect which needs to be considered in studies of these cells from lung lavage. PMID- 2266230 TI - Effect of lidocaine on natural killer activity: rapid inhibition of lysis. AB - We have previously found that NK cell activity is present in rat lung lavage and inhibited by lidocaine. The purpose of this report is to characterize further the inhibition by lidocaine on NK activity. Peripheral blood lymphocytes from normal human volunteers were assayed in a four-hour 51chromium release assay in the presence of varying concentrations of lidocaine during or prior to the lytic assay. During the assay, increasing concentrations of lidocaine inhibited NK activity. This effect was not related to pH and at high concentrations was unrelated to methylparaben found in topical lidocaine. Preincubation of effector cells for one hour with different concentrations of lidocaine produced similar results which were temperature dependent and related to incubation time. Preincubation of effector cells in lidocaine (0.5g%) for one to ten minute intervals at 37 degrees C resulted in 60 to 92% inhibition, respectively. The lidocaine did not alter effector cell viability nor did it affect the phenotypes of the effector cells as determined by flow cytometry. Lidocaine's inhibition of NK activity remained the same for cells which were further purified by plastic adherence, nylon wool filtration and percoll density centrifugation. The effect was not reversed by a 16 hour incubation in tissue culture medium. In a single cell assay, we determined that the inhibition was at the level of cell lysis. PMID- 2266231 TI - Augmentation of host defense against bacterial infection pretreated intraperitoneally with an alpha-glucan RBS in mice. AB - Protection against Listeria monocytogenes and Escherichia coli in mice was enhanced by an intraperitoneal (i.p.) administration of polysaccharide "RBS". Peritoneal macrophages from mice administered i.p. with 30 mg/kg doses of RBS 4 days earlier exhibited increased scavenger functions as assessed by in vivo phagocytosis, in vitro intracellular killing and generation of superoxide anion. When cytokine production of the macrophages was assessed by biological assay and Northern blotting analysis, interleukin (IL)-1 production and IL-1 alpha gene expression were significantly increased in macrophages from RBS-treated mice. On the other hand, tumor necrosis factor (TNF) alpha gene was expressed in macrophages from RBS-treated mice at a much reduced level as compared with those in mice treated i.p. with Corynebacterium parvum on 4 days earlier. In correlation with expression of TNF gene in the macrophages, RBS-treated mice were less susceptible to the lethal toxicity of LPS than C.parvum-treated mice. In RBS treated mice, in vivo elimination of bacteria was enhanced at the early phase of infection with L.monocytogenes or E.coli, resulting in augmentation of host defense against these bacterial infection. These results suggest that adequately enhanced activities of macrophages acting as scavenger phagocytes play important roles in the enhanced resistance against bacteria in mice treated i.p. with RBS. PMID- 2266232 TI - Protein A induced abrogation of cyclophosphamide toxicity is associated with concomitant potentiation of immune function of host. AB - This report confirms our previous observation that protein A (PA) of Staphylococcus aureus Cowan I reduces the cyclophosphamide (Cy) induced toxicity. PA treated animals recover quickly from the toxic effects of Cy. We have exhaustively studied the role of specific and nonspecific immunity in the protection of the animals. It was observed that PA helped the animals in the accelerated regeneration of leukocytes of blood (p less than 0.001) and different lymphoid organs like thymus (p less than 0.001), spleen (p less than 0.01) and bone marrow (p less than 0.01). Increased number and function of macrophages was also observed in PA (p less than 0.001) and PA+Cy (p less than 0.001) groups. PA, on one hand enhanced the cell mediated immunity while suppressed the humoral immunity as was assessed by increase in delayed type hypersensitivity response (p less than 0.001) and decreased in plaque forming cells (p less than 0.001), EAC rosettes (p less than 0.001), hemagglutination (p less than 0.001) and hemolysin titre (p less than 0.05). On the basis of above observations we propose that the immunomodulatory activity of PA helped the animals to remain alive in two ways- (1) by early generation of the cells depleted by the Cy thus helping animals to repair the damaged immune system and fast clearance of the toxic metabolites of Cy (2) by temporarily suppressing the cells responsible for humoral immunity which are more susceptible to Cy metabolites. PMID- 2266233 TI - Flavonoid modulation of murine neutrophil cytokinesis. AB - Flavonoids are known to produce a wide range of immunomodulatory effects. In this study, flavone and six hydroxylated analogues were examined for their effect on the FMLP-directed and the random migration of murine peritoneal exudate neutrophils. Flavone significantly (p less than 0.01) inhibits both directed and random migration at an assay concentration of 100 microM. In contrast, fisetin, kaempferol, chrysin, flavonol, morin and quercetin (in decreasing order of activity) significantly (p less than 0.05 to less than 0.01) enhance both directed and random migration at concentrations of 1.0 to 100 microM. Hydrophobicity does not appear to play a key role in the observed compound activity but the number and position of the hydroxyl substitutions might be important. In addition, the [Ca++] modulator chlorpromazine was found to significantly (10 microM; p less than 0.01) inhibit fisetin-enhanced FMLP directed migration. PMID- 2266234 TI - A critical appraisal of electromyography in evaluating esophageal function. PMID- 2266235 TI - The site of recurrent duodenal ulcer. AB - The aim of this retrospective study was to determine the site of recurrent duodenal ulcer in relation to the site of the index ulcer. One hundred and thirty five patients who had recurrent duodenal ulcer after documented healing of an index ulcer were studied. The recurrent ulcer was more likely to occur in the anterior bulb if the index ulcer was anterior (35 of 58 = 60%) than if the index ulcer was not anterior (29 of 77 = 38%, p less than 0.01). However, the likelihood of a recurrent ulcer on the posterior wall of the bulb was not significantly different whether the index ulcer was posterior (11 of 36 = 31%) or not (22 of 99 = 22%, p less than 0.24). Three of 20 patients (15%) who initially presented with bleeding bled again with their recurrent ulcers, compared with eight of 115 patients (7%) who first presented with dyspepsia only (p = 0.39). Thirteen patients were assessed independently by two endoscopists to determine ulcer site. Their assessments concurred for 12 (92%). PMID- 2266236 TI - Is gastric acid responsible for the pain in patients with essential dyspepsia? AB - The pathogenesis of symptoms in patients with essential dyspepsia is not known. Since treatment with H2-receptor antagonists has provided symptomatic relief in some reports, we carried out the present study to investigate whether gastric acid is responsible for symptoms in these patients. Fifty patients with essential dyspepsia and 25 healthy control subjects were studied. After an overnight fast, a nasogastric tube was passed and its tip positioned in the antrum under fluoroscopic control. Normal saline or 0.1 M hydrochloric acid was infused in a randomized, double-blind fashion. Eleven (22%) patients developed pain with acid infusion, but none with normal saline (p less than 0.005). In 10 of these 11 patients, pain recurred on rechallenge with acid infusion but was promptly relieved with infusion of 1 M sodium bicarbonate. None of the healthy controls developed pain on infusion of acid or saline. These observations suggest that acid has a definite role in the pathogenesis of symptoms in some patients with essential dyspepsia, although other factors may also be important. PMID- 2266237 TI - Treatment of duodenitis with cimetidine: a clinical, endoscopic, and histologic study. AB - We studied the effectiveness of cimetidine in the treatment of endoscopically diagnosed duodenitis. Sixty-nine patients with the solitary endoscopic finding of duodenitis (6% of 1,200 patients who underwent fiberoptic endoscopy of the upper gastrointestinal tract in our unit over 3 years) were studied retrospectively: a good clinical response was apparent in 45 of 69 patients treated with cimetidine (65%), and a fair response in another four (6%). In a controlled, randomized prospective study, we evaluated the effectiveness of cimetidine in duodenitis. Statistically significant improvement for the clinical and endoscopic scores was found in 10 patients treated with cimetidine (p less than 0.01). Improvement in the histologic score did not reach statistical significance. No such improvement was demonstrated in seven placebo-treated patients. We believe that duodenitis is a "peptic syndrome," has a good response to cimetidine treatment, and behaves much like duodenal ulcer disease. PMID- 2266238 TI - Colonic volvulus as a complication of celiac sprue. AB - Colonic volvulus has been a rarely reported complication of celiac sprue. We describe two patients with long-standing celiac sprue, one in whom a recurrent sigmoid volvulus developed, and in the other, a cecal volvulus. Following surgery, both are now asymptomatic on a gluten-free diet. The association between celiac sprue and colonic volvulus was first reported in 1953. There have been only a few isolated cases documented, surprisingly so because the two major predisposing conditions for colonic volvulus are often seen in patients with celiac sprue. Colonic bacterial fermentation of malabsorbed carbohydrate (in celiac sprue) leads to excess gas production. Flaccid bowel loops with sigmoid redundancy, a long mesentery, or cecal hypermobility are not uncommon. A motility disorder in celiac sprue has also been proposed. Thus these factors together would suggest that the likelihood of development of colonic volvulus in celiac sprue would be relatively great. The possibility of underlying celiac sprue should be considered in patients with colonic volvulus who have a background history of recurrent abdominal distention or malabsorptive symptoms. PMID- 2266239 TI - Six physicians with inflammatory bowel disease. AB - This essay tells the stories of six physicians with inflammatory bowel disease (IBD) to emphasize how important denial and control become when a physician is a patient. Guilt at the supposed psychosomatic "origin" of IBD suggests that we as physicians should never blame our patients for getting sick. PMID- 2266240 TI - Erythrocyte sedimentation as a measure of Crohn's disease activity: opposite trends in ileitis versus colitis. AB - To test our hypothesis that the erythrocytic sedimentation rate (ESR) correlates well with clinical activity in inflammatory disease of the colon, but not of the small bowel, we stratified 49 Crohn's disease patients according to their anatomic involvement and then measured the correlations between ESR and clinical activity within each of these anatomical subgroups. For 18 patients with Crohn's disease involving primarily the colon, there was a trend toward a direct correlation between clinical score and ESR (p = 0.15). In the 14 patients with Crohn's disease limited to the colon, this direct correlation was even more pronounced and statistically significant (p less than 0.02). By contrast, an opposite trend was observed for patients with small bowel disease. For the 26 patients with disease involving predominantly the small bowel, as well as for the 22 with disease limited to small bowel, there were statistically significant inverse correlations between clinical score and ESR (p less than 0.04). This difference between the directions of the correlations for Crohn's colitis versus ileitis was statistically significant (p less than 0.05). This study provides further evidence for the importance of analyzing putative indications of disease activity separately for each of the protean forms in which Crohn's disease occurs. PMID- 2266241 TI - Bronchopulmonary involvement in ulcerative colitis. AB - We report two cases of pulmonary involvement in ulcerative colitis. The first patient, a 37-year-old woman, had bilateral basal bronchiectasis full of mucopurulent secretion, with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach. The second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection. In the second patient, a sulfasalazine reaction as an etiologic factor was excluded, while in the first this possibility seemed unlikely. Therefore, we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis. PMID- 2266242 TI - Biliary sludge: a critical update. AB - Biliary sludge has been for many years a poorly defined entity, usually with low amplitude, nonshadowing echoes within the most dependent part of the gallbladder, which shift under the influence of postural changes. From a sonographic point of view, the detection of sludge implies the coexistence of small-sized, solid components and of a gel-like embedding material. The chemical nature of biliary sludge has recently been recognized to be predominantly composed of a coaggregate of cholesterol monohydrate crystals and liquid crystalline droplets, and in some cases, such as obstructive jaundice or symptomatic liver diseases, by bilirubin granules, all embedded in a gel matrix of mucous glycoproteins. From a pathogenic point of view, biliary sludge is often associated with biliary stasis, or with conditions characterized by impaired gallbladder contraction, such as prolonged total parenteral nutrition, fasting, and pregnancy. Other causes include mucus hypersecretion, which may favor cholesterol nucleation and crystal growth, and bile infection. Sludge may be an intermediate step in the formation of different types of stones. From an epidemiological point of view, sludge is quite rare in the asymptomatic, free-living population, but may be common in selected series of symptomatic patients. From a clinical point of view, sludge often has a fluctuating course, including frequent disappearances and reappearances, suggesting that the early stages of gallstone formation are reversible. PMID- 2266243 TI - Spontaneous bacterial peritonitis due to Salmonella enteritidis in cirrhotic ascites. AB - Spontaneous bacterial peritonitis due to Salmonella is uncommon. We report three patients with ascites infected by Salmonella. All three patients had advanced chronic liver disease, typically cirrhosis with portal hypertension. Salmonella enteritidis grew in the ascite fluid culture of the three patients. There was no clinical or microbiological evidence of Salmonella infection other than in the ascitic fluid. One patient died before antibiotic treatment was started, but the other two were treated with different combinations of antimicrobial drugs. One of them died on the fourteenth day of hospitalization, and the other survived. PMID- 2266244 TI - Thoracic succussion splash: a new symptom and sign of achalasia. AB - A patient with a "thoracic succussion splash" due to achalasia is described. She noted a splashing or sloshing sensation in her chest related to jogging and bending. On examination a splashing sound could be heard over the mid sternum and the posterior chest when the patient was rocked vigorously back and forth. PMID- 2266245 TI - Spinal epidural abscess: an unusual complication of a duodenal ulcer. AB - A 50-year-old man had several months of progressively worse low-back pain associated with constitutional symptoms and a history of retroperitoneal tumor and bleeding duodenal ulcer. Initial evaluation suggested a lumbar spine tumor, but myelography confirmed the presence of an epidural abscess. Further evaluation revealed a duodeno-spinal fistula at the site of the previous duodenal ulcer, which proved to be the cause of the abscess. PMID- 2266246 TI - Hypergastrinemia, gastric endocrine cell hyperplasia, and intractable diarrhea. AB - A patient with pernicious anemia developed severe intractable diarrhea night and day. Investigation revealed chronic atrophic gastritis and a markedly elevated level of serum gastrin. No obvious explantation for the diarrhea was found, but after antrectomy, the gastrin level returned to normal and the diarrhea subsided. Possible mechanisms for an association between diarrhea and hypergastrinemia include colonic hypermotility secondary to release of acetylcholine and inhibition of fluid and electrolyte reabsorption within the small bowel. PMID- 2266247 TI - Ileal duplication cyst causing massive bleeding in a child. AB - Intestinal duplication is a rare congenital anomaly; nonetheless, it comprises more than half of all alimentary duplication disorders. Our case report describes the hemorrhagic sequelae of this entity with surgical and pathologic findings. A review of anatomical classification, embryology, and natural history of duplication cyst follows; differentiating characteristics of duplication cyst versus Meckel's diverticulum are outlined. Intestinal duplication cyst should be considered in the differential diagnosis of GI bleeding, especially in children. PMID- 2266248 TI - Coumadin-induced gastrointestinal hemorrhage associated with an ileal duplication. AB - A 31-year-old man had recurrent gastrointestinal hemorrhage after aortic valve replacement and initiation of anticoagulation therapy with coumadin. Radionuclide bleeding scan and subsequent contrast angiogram demonstrated a site of hemorrhage in the distal ileum, and at surgery a 1.8-cm spherical duplication was found. On histologic examination, the duplication was lined with normal ileal mucosa, and near the mouth of the duplication an inflammatory ulceration proved to be the site of hemorrhage. In a young patient with anticoagulation-associated gastrointestinal hemorrhage, alimentary tract duplication should be considered. PMID- 2266249 TI - Small bowel obstruction associated with a leiomyomatous uterus. A case report and review of the literature. AB - A 38-year-old woman developed small bowel obstruction shortly after a cholecystectomy because of a massively enlarged leiomyomatous uterus. Small bowel obstruction is a relatively rare complication from fibroid tumors and results from entrapment of the bowel between serosal pedunculated fibroids (as in this patient), adhesions to infarcted leiomyomas, or from compression of the small bowel by the large mass. Large uterine leiomyomas clearly must be considered in the etiology of intestinal obstruction. PMID- 2266250 TI - The management of postoperative chylous ascites. A case report and literature review. AB - Chylous ascites remains rare as a complication of surgical intervention. Although therapeutic manoeuvres to control chylous ascites have been developed over the past 20 years, its pathophysiology is poorly understood. Conservative approaches involving dietary restriction of long-chain triglycerides and salt, together with multiple paracenteses, are still the therapies of choice. Persistent chylous ascites may be treated surgically by ligation of leaking lymphatics or implantation of a peritoneovenous shunt once the lymphatic anatomy has been defined by preoperative investigations. We report a case of chylous ascites developing after laparotomy and duodenotomy for obscure gastrointestinal bleeding, which did not respond adequately to medical therapy and was successfully managed by the insertion of a peritoneovenous shunt. PMID- 2266251 TI - Idiopathic sclerosing peritonitis in a man. AB - Idiopathic sclerosing peritonitis is a rare disease described in young adolescent women, characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel. Here we describe a 35-year-old man who underwent exploratory laparotomy for repeated small bowel obstruction. Only partial resection of the terminal ileum was possible because of adhesions; recurrent abdominal infections and leakage from anastomosis required further resection, which ultimately resulted in short bowel syndrome and malabsorption. The clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis. We review the relevant literature, to confirm, to the best of our knowledge, that this is the first report of a male patient who has developed this rare disease. PMID- 2266252 TI - Cystic mesothelioma of peritoneum: occurrence in a man. AB - We report a case of cystic mesothelioma of the peritoneum in a 54-year-old man in whom cystic masses were removed twice by surgery at an interval of 2 years. The patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer. The pathogenesis of the disease is uncertain, but we consider it neoplastic of low grade malignancy. PMID- 2266253 TI - Neuromesenchymal hamartoma of the small bowel. AB - We present the case of a long small bowel stricture with pathological features similar to those described as "neuromuscular and vascular hamartoma," showing in addition extensive fatty submucosal infiltration and fibrous intramural nodules. In the controversy about the nature of this disorder, we consider it a separate entity. Taking into account that other mesenchymal tissues than the originally described can participate, we propose the alternative term of "neuromesenchymal hamartoma" of the small bowel. PMID- 2266254 TI - Sibship Crohn's disease and ankylosing spondylitis. PMID- 2266255 TI - Perforated gastric ulcer in hiatal hernia. PMID- 2266256 TI - Diagnostic value of UGI radiography. PMID- 2266257 TI - Safety of midazolam and diazepam for conscious sedation. PMID- 2266259 TI - Childhood disability. PMID- 2266258 TI - Acute renal failure in nonfulminant hepatitis A. PMID- 2266260 TI - Rehabilitation: the ultimate aim. PMID- 2266261 TI - Conservative management of flail chest. AB - A total of 100 cases of flail chest were studied to find out the efficiency of the anti-lung contusion regimen containing a diuretic, a steroid and an enzyme preparation for some 10 days, along with pad and strapping. There were 80 males and 20 females. Majority (71%) of patients were between 16 and 45 years. Road side accident was the commonest cause, present in 65% cases followed by bull horn injuries (25%), fall from a height (8%) and gun shot injuries to chest (2%). Associated intrathoracic and extrathoracic injuries were recorded in 45% and 30% cases respectively and they were treated according to their merits. There were 11 deaths with an overall success rate of 89%. PMID- 2266262 TI - Labetalol and nifedipine in the management of essential hypertension. AB - Antihypertensive effects of labetalol and nifedipine were evaluated in a double blind cross over trial in ambulatory patients with moderately severe hypertension (mean diastolic BP 101.2 +/- 1.78 mm Hg, 105 +/- 2.15 mm Hg respectively and mean systolic BP 164.2 +/- 4.2 mm Hg and 171.4 +/- 5.82 mm Hg respectively in each group of 10 patients). The effect of labetalol over the systolic and diastolic BP was highly significant (p less than 0.01). The effects of nifedipine on systolic and diastolic BP were also significant but effects on diastolic BP was highly significant (p less than 0.01). In cross over study it was seen that nifedipine was not much superior in lowering the systolic BP whereas diastolic BP was lowered to a significant level (p less than 0.05) as compared to labetalol. PMID- 2266263 TI - Clinicobacteriological study of empyema thoracis in infants and children. AB - Forty-one cases of empyema thoracis admitted in hospital during April, 1985 to August, 1987 were studied. Majority were males (65.9%) and were of less than 2 years of age (70.7%). Right side (60.9%) was predominantly involved. Abdominal distension (43.9%) was very characteristic, with other usual features like fever, cough and respiratory distress. A large majority of them were victims of malnutrition (73.2%) and anaemia (53.7%) with haemoglobin level ranging from 5-9 g/dl. Mortality was high (17.1%). Therapy with parenteral cloxacillin and gentamicin and continuous intercostal tube drainage accounted for loss of 15.8 bed days (average period of hospitalisation). Staph aureus was the principal aetiopathogen (68.3%). No anaerobe could be isolated. Strains of staphylococci were mostly resistant to penicillin and ampicillin but sensitive to gentamicin, cloxacillin and erythromycin. PMID- 2266264 TI - Nalidixic acid in diarrhoea. AB - In a private practice set-up from June 21, 1982 to December 31, 1984, 109 children who were admitted to the hospital with acute bacterial diarrhoea diagnosed on the basis of clinical findings and faecal leucocytes over 10/high power field, were treated with nalidixic acid 55 mg/kg in 4 divided doses to find out its effectiveness. The youngest in this study group was of 18 days, the oldest was of 16 years and the mean age was 2.61 years. In this group 72 were male children and 37 female. The average duration of stay in hospital was 2.71 days. Before admission 40 children (36%) had prior antimicrobial treatment elsewhere. These children were re-evaluated 14 hours after treatment and clinical improvement was observed in most of the cases. It was found that nalidixic acid was an effective and safe antimicrobial agent in acute infectious diarrhoea. It cut down the days of hospitalisation and cost. It was well tolerated even in children less than 3 months. PMID- 2266266 TI - An unusual power take-off injury to genitalia. PMID- 2266265 TI - Morbidity and mortality of acute myocardial infarction in and around Aligarh. AB - A 6-year retrospective study of 341 cases of acute myocardial infarction admitted to JN Medical College Hospital, Aligarh in respect of the incidence, complications and mortality in relation to age, sex, religion, smoking habit occupation and risk factors was made. The incidence was found to be 9 per 1000 hospital admissions. Maximum number of cases was in the age group of 51-60 years and male to female ratio was 7:1. There was no significant difference in incidence and mortality between Hindus and Muslims of both sexes. Highest incidence was noted among sedentary workers and smokers. Hypercholesterolaemia was found in only 17.01% cases, the rest having normal serum cholesterol levels. Hypertension and diabetes mellitus were associated in 24.05% and 12.32% cases respectively. Cardiac complications were noted in 43.4% of patients, the commonest being cardiac failure. Overall in-hospital mortality was observed to be 11.41% of which 79.49% had cardiac complications. Diabetics had significantly (p less than 0.05) higher mortality rate (21.43%) as compared to non-diabetics. Smokers had higher mortality rate compared to non-smokers (p less than 0.01). Although those with hypertension and with hypercholesterolaemia had higher mortality, the results were not statistically significant. The average day of expiry after acute myocardial infarction was 3.82 days during hospital stay. PMID- 2266267 TI - Incomplete faciomandibular dysostosis with congenital facial palsy. PMID- 2266268 TI - Unexplained infertility: a challenging problem. PMID- 2266269 TI - Ocular manifestations of acquired immune deficiency syndrome. PMID- 2266270 TI - Drugs during pregnancy. PMID- 2266271 TI - Eye protectors. PMID- 2266272 TI - Altered expression of HLA-A,B specificities on acute lymphoid and myeloid leukaemia blasts. AB - HLA-A,B specificities were analysed on the neoplastic blasts of a panel of 69 lymphoblastic (ALL) and 50 non lymphoblastic (ANLL) acute leukaemias at onset using the standard lymphocytotoxicity technique. Analysis of the number of detected specificities per locus and, when possible, comparison of the results with those obtained on lymphocytes of the same patients during remission revealed many alterations in the expression of A,B specificities including extra specificities both at the HLA-A and -B loci mainly on lymphoblasts and missed specificities mainly at the HLA-B locus on myeloblasts. Lack of A,B antigens was complete in 6.2% of all tested samples (9% of ANLL) and selective for all the products of one locus in 16.8% of all tested samples (27.7% of ANLL). A decrease of class I molecules on the cell surface was evidenced with MoAb W6/32 on blasts missing detectable serological specificities. PMID- 2266273 TI - Molecular analysis of H-2 class I molecules expressed on the UV-induced tumour 1591. AB - We have biochemically characterized by 2D (two-dimensional) electrophoresis three novel class I molecules called A166, A149 and A216 expressed by 1591, a UV induced fibrosarcoma, and have compared them to class I molecules expressed by mice of the H-2q and H-2s haplotypes. A166 and A149 are very similar if not identical to Dq and Lq respectively. We have shown, using HPLC (high-pressure liquid chromatography) tryptic peptide mapping, that the expression of A166 is approximately three fold greater than A149, reminiscent of Dd compared to Ld. In addition A216 possess an identical isoelectric point to that of the Ks molecule. We demonstrate that outbred Swiss Webster mice express an analogous constellation of class I molecules and we conclude that our results can be most easily interpreted in terms of an allogeneic origin for the novel class I molecules expressed on 1591. PMID- 2266274 TI - Insulin-dependent diabetes mellitus secondary to chronic pancreatitis is not associated with HLA or the occurrence of islet-cell antibodies. AB - We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes. PMID- 2266275 TI - [Surgical treatment of ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia and their long follow-up results]. AB - We have treated surgically the drug-refractory ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular dysplasia. The early and late results of the cryoablation were studied. We operated 8 patients. They showed 10 clinical VTs. A total of 21 VTs were detected (17 VTs during preoperative EPS, 4 VTs during intraoperative EPS). 19 VTs were operated: the origins of 15 VTs were determined by the intraoperative mapping, while those of 4 VTs were suspected by the preoperative EPS. During the follow-up time (mean 3.25 +/- 1.46 years), no patient died, VTs recurred in 2 patients and a new VT was seen in one patient. No recurrence was recognized in 12 VTs operated with the cryoablation applied from the endocardial side, but 4 out of 7 VTs recurred which were operated from the epicardial side. Cardiac arrest induced by aortic clamping didn't affected the efficacy of the cryoablation in the case of epicardial approach. CTR increased slightly postoperatively, from 49.9 +/- 4.4% to 53.3 +/- 5.3% at the 29.2 +/- 15.9 pom. No patients showed the signs of congestive heart failure postoperatively and required the medication except the patients with VT recurrence and a patient with the atrial flutter-fibrillation. In conclusion, even though this disease has the difficulty in the eradication of arrhythmia, VTs actually threatening the patient life at present could be cured by the cryoablation from the endocardial side. PMID- 2266276 TI - [Mediastinal infection after open cardiac surgery]. AB - Mediastinal infection is a rare but life-threatening complication after open cardiac surgery. Of 852 patients undergoing cardiac operations performed with a median sternotomy between January of 1981 and August of 1989, 19 patients (2.2%) developed deep sternal infections with mediastinitis, and 6 of them (31.6%) died. Tissue cultures were obtained from all but three patients, and staphylococcus aureus was the most frequent infecting organism associated with high mortality rates (3/8). 18 patients were managed with debridement and irrigation as the primary treatment, but 4 of them developed infective endocarditis during the course of irrigation treatment and then died. After 1987, 6 patients, who didn't gain wound closure with irrigation alone, were treated with reconstructive techniques, one with pectoral muscle flap closure, another with rectus myocutaneous flap mobilization, and the remainder with omental transfer respectively. All of them achieved eradication of infection as well as wound closure. Then we have advocated early debridement and mobilization of viable tissues such as omentum into the mediastinum. PMID- 2266277 TI - [Clinical results of open heart surgery within 2 weeks after cardiogenic embolic stroke]. AB - Fourteen patients, 5 with infective valvular disease (IVD), 7 with non-infective valvular disease (NVD) and 3 with LA myxoma, underwent open heart surgery within 2 weeks after cardiogenic embolic stroke because of uncontrolled heart failure or recurrent embolism. Fifty percent of patients experienced a second embolism within 2 weeks of the initial stroke. Preoperative brain CT revealed no hemorrhagic infarction in all patients. However, in 3 of 5 patients with IVD, who had large brain infarction, one patient died from massive brain edema and two patients from severe brain hemorrhage. The other 2 patients with IVD, who had small infarction, and the remaining 7 patients with NVD and LA myxoma, even having large or small infarction, recovered without any complications. From these results, we concluded that 1) Open heart surgery within 2 weeks after initial stroke was safe in patients with no brain infarction and small non-hemorrhagic infarction, 2) Patients with IVD should be treated surgically before embolic stroke, because mortality rate was so high even in patients with non-hemorrhagic infarction. PMID- 2266278 TI - [Tricuspid annuloplasty--modified technique]. AB - A modification of the DeVega's tricuspid annuloplasty (TAP) in the treatment of tricuspid regurgitation (TR) is described. Using a double-ended 2-0 Ethibond suture buttered with a Teflon felt pledget, a double suture line is begun at the center of the annulus of the anterior tricuspid valve leaflet. The two suture lines 2 to 3 mm apart are run around the edge of the annular ring of the anterior and posterior tricuspid valve leaflets, going over the posteroseptal commissure by 1.5 cm. A tiny piece of Teflon felt is placed at the end of the sutures. The annulus is narrowed to sungly allow passage of a prove with a diameter of 28 or 30 mm. The tricuspid function is assessed by injecting saline into the right ventricle through the right atrium. Between March 1986 and July 1989, 28 patients with functional TR secondary to mitral valve diseases have been operated on by this technique. There are one early and one late deaths, none being related to tricuspid valve annuloplasty. All 26 survivors had a significant drop in right atrial pressure and an associated improvement in clinical status. Follow-up of the 27 patients who survived this TAP ranges from 2 to 38 months (mean 17 months). This annuloplasty is a safe, effective and readily teachable method for the surgical management of TR. PMID- 2266279 TI - [Electrophysiological evaluation of retrograde cardioplegia--experimental study of efficacy for the right ventricle]. AB - Recently, coronary artery bypass grafting operations for patients with total proximal multi-vessel coronary obstructions are increased. In these cases, antegrade cardioplegia through the aortic root has been applied as usual. But it seems to be difficult to deliver cardioplegic solution to myocardium uniformly beyond coronary stenosis. Retrograde coronary sinus cardioplegia in the presence of proximal coronary artery obstruction could maintain improved cardioplegic delivery and satisfactory myocardial protection. Because of the limitation of antegrade cardioplegia, retrograde cardioplegic technique has, once again, been cited as a reasonable alternative to antegrade cardioplegia. But on the other hand, retrograde cardioplegia includes the potential for relatively inadequate preservation of right ventricle based on the venous drainage communication to the coronary sinus. The object of the present work is mainly to evaluate the efficacy of retrograde coronary sinus cardioplegic technique for right ventricle by electrophysiological method. Thirty-six adult mongrel dogs divided three groups. Sixteen animals (Group I) received GIK cardioplegia through the coronary sinus, thirteen animals (Group II) received GIK added diltiazem cardioplegia through the same way, and seven animals (Group III) received GIK cardioplegia through aortic root. No large temperature gradients of myocardium between right and left ventricle in each group and also temperature gradients of right ventricle between three groups have been observed. The time duration from starting of injection of cardioplegia to disappear the electrical activity in right and left ventricle were 11.4 +/- 8.2, 3.4 +/- 1.2 minutes in group I, 2.9 +/- 1.5, 2.2 +/- 1.4 minutes in group II, and 0.9 +/- 0.4, 0.9 +/- 0.2 minutes in group III. The time duration from starting of injection of cardioplegia to reappear the electrical activity in right and left ventricle were 6.4 +/- 8.7, 13.4 +/- 7.9 minutes in group I, 20.0 +/- 3.5, 21.3 +/- 1.6 minutes in group II and 18.0 +/- 5.5, 18.7 +/ 4.5 minutes in group III. Unipolar peak-to-peak amplitude (UPPA) analysis reveals the condition of myocardial preservation during ischemic arrest and we compared preischemic UPPA with post-ischemic UPPA. In group I, UPPA declined of 44.1 +/- 29.3% in right ventricle and 72.7 +/- 27.6% in left ventricle, in group II, 78.7 +/- 28.7%, 81.9 +/- 23.6%, in group III, 71.4 +/- 18.7%, 76.7 +/- 9.89%. Analysis of ultrastructural changes in the myocardium are shown that injury was most manifest in the right ventricle of group I, but in group II, ultrastructure of right ventricle maintained nearly normal condition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266280 TI - [Characteristic difference of functional tricuspid regurgitation between acquired valvular heart disease and atrial septal defect]. AB - The characteristic difference in functional tricuspid regurgitation (TR) was studied between acquired valvular heart disease (VHD) and adult atrial septal defect (ASD). Fifty patients of VHD and 20 patients of ASD were subjected to this study. In all patients, the TR volume per beat (VTR) was calculated with our original method using 2-dimensional color Doppler (2-DD) and continuous-wave Doppler (CW) echocardiographies. VTR is obtained by the product of the cross sectional areas (S) of the base of regurgitant jet in 2-DD and the regurgitant volume of one unit area (Vu) in CW (VTR = 1/3.S.Vu). The preoperative evaluation of TR according to VTR showed a good relationship with the operative findings, and the patients with preoperative VTR greater than or equal to 10 cc were candidates for tricuspid valve repair. In all patients with preoperative VTR less than 10 cc (18 patients of VHD and 10 patients of ASD), VTR decreased postoperatively without any tricuspid valve repair. In patients with VTR = 10-20 cc (19 patients of VHD and 5 of ASD), VTR showed a decrease to below 10 cc after tricuspid annuloplasty (TAP) by Kay's method in 18 patients of VHD and 5 of ASD, and with no tricuspid valve repair in one patient of VHD. In patients with VTR greater than or equal to 20 cc (13 patients of VHD and 5 of ASD), the postoperative VTR diminished to below 10 cc after Kay's TAP in 8 patients of VHD and 5 of ASD, and VTR disappeared after valve replacement (TVR) in 2 patients of VHD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266281 TI - [Effects of coronary revascularization on infarcted myocardial regions- evaluation on postoperative left ventricular regional wall motion during exercise]. AB - In order to determine the effects of coronary revascularization for infarcted regions on postoperative left ventricular function and regional wall motion, we studied first-pass radionuclide angiography at rest and during exercise before and after operation in 18 patients with previous myocardial infarction. Preoperative mean value of left ventricular ejection fraction (LVEF) was significantly decreased during exercise from 56.8 +/- 14.1% to 46.1 +/- 15.5% (p less than 0.01). Postoperatively, there was no change of the values between at rest and during exercise: 53.6 +/- 14.1% versus 51.9 +/- 15.7%. Postoperative mean LVEF during exercise was significantly higher, compared with that of preoperative LVEF (p less than 0.05). Mean regional ejection fraction of infarcted regions was significantly decreased during exercise from 66.0 +/- 15.0% to 56.1 +/- 15.8% (p less than 0.01) before operation. However, there was no significant change in values between at rest and during exercise after operation: 65.4 +/- 13.9% versus 61.8 +/- 14.5%. Mean postoperative regional ejection fraction during exercise was significantly higher, compared with preoperative regional ejection fraction after operation (p less than 0.05). These results might be indicated that regional wall motion of the infarcted regions with ischemia enhanced by exercise preoperatively can be definitely improved by coronary revascularization. PMID- 2266282 TI - [The influence of A-V synchrony and changes in heart rate on rate responsive pacing]. AB - To evaluate the hemodynamics during physiological cardiac pacing, influence of A V synchrony, changes in heart rate and physical exercise on cardiac function were studied. In observing the effects of increasing heart rate in acute cases, C1, mAp, PaWP, and CVP show a clear improvement with physiological pacing (AAI or DVI). However, SSS cases with VVI pacemakers show a clear decline in cardiac function with increased heart rate. EF and ER, which indicate ventricular contractility, showed improvement with physical exercise and increased heart rate under physiological pacing, but actually decreased under VVI pacing. PFR, which indicate diastolic function, showed an identical tendency. Thus, it was concluded that: 1. The most important factor affecting cardiac function during pacing is A V synchrony, followed by increased heart rate and physical exercise. 2. VVI pacing at high pacing rates showed an adverse influence on cardiac function. This was mostly observed in VVI pacing for SSS cases. 3. Thus, we may recommend AAIR pacing for SSS with normal A-V conduction, and DDD pacing for SSS cases with abnormal A-V conduction on CAVB without Af. PMID- 2266283 TI - [Transaortic myectomy for hypertrophic obstructive cardiomyopathy--efficacy of intraoperative pressure measurement]. AB - The many aspects of postoperative course of hypertrophic obstructive cardiomyopathy (HOCM) have been apparent, while many studies concerning long-term follow up have been published in recent years. Many surgical approaches have been performed but recently transaortic subvalvular myectomy is most common. This study reviews 22 patients with HOCM operated on between 1984 and 1989. Transaortic approach was used for all adult patients. One patient had a complication with an iatrogenic VSD, which was closed by Dacron patch during the procedure. There was one hospital death; She is a 67 year-old woman who died due to an acute abdomen. All 14 patients followed up over 3 months had significant functional improvement. Our retrospective study suggests that myectomy in patient with HOCM seems to be not only palliative but curative operative method. Left atrial- and left ventricular dimension tended to normalize in the postoperative course. The intraoperative estimation of Brockenbrough phenomenon is effective to assess the release of left ventricular outflow obstruction. PMID- 2266285 TI - [Mitral valve replacement with preservation of ventricular annular continuity]. AB - We evaluated clinical effects of mitral valve replacement with preservation of ventricular annular continuity in 53 patients with isolated mitral stenosis and regurgitation. The patients were divided into 3 groups; Group 1: the patients had conventional mitral valve replacement, Group 2: with preservation of posterior leaflet ventricular annular continuity (VAC) (33 patients), and Group 3: preservation of both anterior and posterior leaflet (8 patients). Operative technique was described for pure mitral regurgitation and mitral stenosis. There was one patient died within 30 days operatively in each group. In Group 1 the patient died for poor LV function, in Group 2, the patient died for postoperative GVHD, and in Group 3, the death caused by postoperative LV rupture. We have observed no late death. Minor thromboembolization in early stage were seen in 2 cases of Group 2 and there were no apparent correlation with operative technique. Postoperative cardiac catheterization data (Pulmonary Artery wedge pressure, C.O, LVEF, LVEDV1) showed no significant difference among these 3 groups. Segmental wall contraction in left ventriculography demonstrated good contraction in Group 2 and Group 3 compared with that of Group 1. Left ventricular contraction index with heart rate corrected mean Vcf (Vcfc) and left ventricular end-systolic wall stress (sigma es) relation using two dimensional cardiac echogram demonstrated almost normal range in the groups 2 and 3. These findings suggests that mitral valve replacement with preservation of ventricular annular continuity has beneficial effects on postoperative left ventricular function and requires to be further investigated. PMID- 2266284 TI - [Clinical results, graft patency and flow reserve capacity of multiple coronary artery bypass with bilateral or sequential internal thoracic artery grafts]. AB - Multiple coronary artery bypass grafting (CABG) was performed utilizing the internal thoracic arteries (ITA) in 87 patients ranging in age from 3 to 76 years. Bilateral ITAs were used in 67, sequential grafting was performed in 16, and the combination of both techniques was applied in 4 patients. Twelve patients had coronary arterial obstructions due to Kawasaki disease (mean age 9.7 +/- 3.3 years) and the remaining 75 patients had atherosclerotic coronary artery disease (mean age 53 +/- 10 years). Triple vessel disease and left main trunk disease occupied 85% of the patients. The number of grafts was 2 to 5 per patient with an average of 3.2 +/- 0.7 per patient. In bilateral ITA grafting, the combination of the RITA to LAD and LITA to LCX was most frequently used, and in sequential grafting, the LITA-diagonal artery-LAD was the most common use. There were no early or late mortalities in the present series. The patency rates for the RITA and LITA were 93% and 96%, respectively, and those of sequential grafting were 100% in both the proximal and distal anastomoses. The clinical outcome of multiple CABG with ITAs was quite satisfactory, and the bilateral ITAs could be used in the very wide range of patient's age from 3 to 76 years. In addition, blood flow reserve provided by bilateral ITAs was equivalent to that of the SVG alone or SVG plus ITA on the basis of the result of coronary sinus flow (CSF) measurements during exercise, and thus complete revascularization of the left ventricle could be accomplished by multiple CABG with ITAs. PMID- 2266286 TI - [A report of successful treatment of mediastinitis and graft infection after ascending and aortic arch reconstruction]. AB - A 43 years old male patient had composite graft replacement of ascending aorta and aortic arch with total reconstruction for his aortic valve regurgitation and ascending and aortic arch aneurysm. He developed high fever leucocytosis and in the early postoperative period and was diagnosed as aorta mediastinitis by proving bacterial culture positive in blood as well as in the drainage fluid. Re exploration of mediastinal cavity was carried out and the necrotic tissues were removed as much as possible. The mediastinal cavity, especially around the graft was also thoroughly irrigated and washed with Iodine (Isozin) solution. Following this, mediastinal cavity was packed with non-diluted solution of Iodine sponge. Thereafter mediastinum was left open by applying sprint and patient was brought back to ICU. He was kept controlled ventilation and deep sedation. Mediastinal cavity was irrigated and re-packed with same solution every 8 hours for the following 48 hours so as to expect complete disinfection of the mediastinal cavity. He was brought back to the operation room again and midsternal incision was extended to the abdomen. Half portion of the major omentum was isolated from the stomach and transplanted into the mediastinal cavity with its vascular supply. Special care was taken to wrap around the graft with omentum. The sternum and skin were closed without any drainage tube. As postoperative complications most probably related to the application of high concentration of Iodine solution, he developed severe hepatic failure for which he was treated with hemofiltration. This was gradually improved and the infection was well controlled. He was discharged from the hospital on the 77th postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266287 TI - [Coronary artery bypass grafting for a very rare run off case of superdominant left anterior descending artery]. AB - A superdominant left anterior descending artery (LAD) was found in a 59-year-old man who had electrocardiographic evidence of acute anterior and inferior wall myocardial infarction. Coronary cineangiography showed 95% stenosis at segment 7 of LAD which extended around the apex, ascending into the posterior interventricular sulcus to the crux and ran to the left into posterior atrioventricular sulcus. Posterior descending artery was not provided by the left circumflex artery or the right coronary artery. Multiple infarction due to proximal disease of such a superdominant LAD is very rare in pathoanatomically. Coronary artery bypass grafting to the LAD using left internal mammary artery was performed. The patients is now doing well with no anginal attack, 18 months following the operation. PMID- 2266288 TI - [A case of extended myocardial infarction treated with the left ventricular assist device (LVAD) before and after the operation--the value and limitation of LVAD]. AB - A left ventricular assist device (LVAD) was applied to a patient who had profound left ventricular failure following extended myocardial infarction caused by the left main trunk obstruction. The patient was a 61-year-old man, who had severe chest distress and was admitted 11 hours after the onset of the symptom. At the time of admission, he was already in cardiogenic shock. The emergent coronary angiography showed complete obstruction of the left main trunk and the intact right coronary artery which had no collateral flow to the left coronary artery. The intraaortic balloon pumping (IABP) was started bu could not maintain the satisfied circulation. Then a LVAD was applied to the patient 5 days after the onset. The LVAD maintained the normal circulation and prohibited exaspiration of organ failure. 19 days after the onset, scartectomy and A-C bypass to LAD was performed. The patient could not be weaned from LVAD and died of right ventricular failure following ventricular arrhythmia 20 days after the installation of LVAD. The use of LVAD for nonoperative cardiogenic shock is rare. Circulatory support with a LVAD in the treatment of a patient in cardiogenic shock following a acute myocardial infarction was considered useful. PMID- 2266289 TI - [A case of successful surgical treatment of DeBakey IIIb dissecting aortic aneurysm with the true lumen obstruction of the thoracic descending aorta]. AB - A case of successful surgical treatment of DeBakey IIIb dissecting aortic aneurysm with the true lumen obstruction of the thoracic descending aorta is presented. A 64-year-old male was admitted to our hospital with a complaint of severe chest and back pain. Immediately antihypertension therapy was carried out. But, after 14 days, acute renal failure was occurred by the true lumen obstruction of the thoracic descending aorta. On the 78 days after hospitalization, the flow reversal thromboexclusion by ascending aorta-abdominal aorta bypass and permanent aortic clamping was done. The reasons why this procedure was selected are as follows: 1) widely extended dissection, 2) renal failure, 3) poor pulmonary function, 4) left hemiparesis due to apoplexy. The post-operative course was excellent, paraplegia did not occur and renal function improved very well. The post-operative CT revealed thrombi formation within the thoracic descending aorta. PMID- 2266290 TI - [Cerebral and myocardial infarcts due to deterioration of cloth-cover of Starr Edwards mitral valve 16 years after replacement]. AB - A 55 year-old woman whose mitral valve had been replaced 16 years previously with a Starr-Edwards cloth-covered ball valve was admitted to our hospital, complaining of memory disturbance and bilateral pretibial edema. Her CT scan findings showed a low density area in the left anterior and temporal lobes, hippocampus, and insula. A right coronary angiogram demonstrated total obstruction at the midportion. In addition to these cerebral and myocardial infarctions due to cloth-wear of the Starr-Edwards ball valve, her laboratory data indicated intravascular hemolysis. Her malfunctioning Starr-Edwards valve was successfully replaced with a Bjork-Shiley valve. An aggressive attitude toward urgent replacement is suggested in cases of suspected cloth-wear. PMID- 2266291 TI - [Total occlusion of proximal left main and right coronary artery]. AB - Total occlusion of the left main coronary artery (LMT) is rarely demonstrated with coronary angiography. All patients with LMT occlusion are of necessity dependent upon collateral circulation from the right coronary artery, which in approximately two thirds of patients is jeopardized because of marked obstruction of the right coronary artery. The ultimate example of collateral flow is provided by the following case. A 64-year-old man, who had total proximal left main and right-coronary artery occlusion, underwent coronary artery bypass grafting. On coronary angiogram, his jeopardized collateral artery was conus branch and only the LAD was graftable for coronary artery bypass surgery. One saphenous vein graft was bypassed to the LAD. Postoperatively, the left ventricular function improved considerably and the ejection fraction of the left ventricle rose to 46% from 23% preoperatively. PMID- 2266292 TI - [Primary malignant hemangioendothelioma of the aorta--a case report]. AB - An extremely rare case of primary malignant hemangioendothelioma of the thoracic aorta in a 54-year-old woman was reported. The patient was diagnosed as having an aneurysm of the thoracic aorta, and was operated on accordingly. The defect of the aortic wall was closed with a patch of woven Dacron prosthesis. Malignant cells were found postoperatively in the wall of aneurysm. Further immunohistochemical studies of the specimen revealed positive for factor VIII related antigen, thrombomodulin, and Ulex europaeus agglutinin-1. The data suggested hemangioendothelioma. Reoperation in the twelfth postoperative month was unsuccessful. She died of respiratory failure 13 month after the initial surgery. Immunohistochemical studies are required for the correct diagnosis of vascular tumors. An aggressive surgical intervention is necessary as the only means of treatment. PMID- 2266293 TI - [Nonischemic ventricular tachycardia with coronary arterio-venous fistula]. AB - A 22 year-old man who suffered ventricular tachycardia (VT) during 8 years was admitted to our hospital for treatment of VT. He also had diseased, coronary arterio-venous fistula with a mild L-R shunt and coronary fistula was closed operatively 4 years ago because it was presumed to be a cause of VT, but the VT remained after the closing on the fistula. After admission in our hospital, catheter endomyocardial mapping and coronary cineangiography were undergone and revealed that the coronary artery was intact and a pre-excitation area located in the LV apico-lateral wall. Dual catheter ablations were attempted but resulted in failure. Then, surgical cryoablation was employed under the use of extracorporeal circulation, following epicardial and endocardial mapping. Cryoablation (-150 degrees C) to the postero-septal wall of LV could terminate VT completely. PMID- 2266294 TI - [A case of right ventricular failure after CABG successfully supported by right heart bypass with a centrifugal pump]. AB - A 67-year-old woman underwent CABG because of severe triple vessel disease. She could not wean from CPB in spite of full inotropic drugs and IABP support due to right ventricular failure probably caused by the perioperative right ventricular infarction. Right heart bypass (RHB) with a centrifugal pump was used. Finally she could wean from CPB and took an uneventful postoperative course except mediastinitis. During 5 days of RHB operation ACT was maintained between 180s and 200s by systemic heparinization. RHB with a centrifugal pump is a reliable method to assist a failing right ventricle. PMID- 2266295 TI - [Valve replacement in infective endocarditis with mycotic aneurysm]. AB - We successfully performed craniotomy and mitral valve replacement on a patient with bacterial endocarditis and ruptured intracranial aneurysm. A 15-year-old woman with fever and heart murmur was admitted to another hospital. Infective endocarditis and mitral valve regurgitation was diagnosed and treated with antibiotics. About one month after admission the patient suddenly showed severe headache and hemiparesis. Brain CT demonstrated intracerebral and subarachnoidal hemorrhage. The patient was unconscious when transferred to Mitsui Memorial Hospital where cerebral angiography showed anterior cerebral aneurysm and echocardiography showed mitral valve vegetation. We judged the necessary mitral valve replacement could be delayed until the aneurysm had been stabilized. We therefore began treatment using a different antibiotic but, in spite of this, 10 days later the aneurysm had enlarged dramatically. As conservative treatment was ineffective, a clipping operation was done to prevent re-rupture at the time of mitral valve replacement which could not be delayed much longer. 10 days later, cerebral 4 vessel study was done which showed no abnormality. Mitral valve replacement was then done and the patient was discharged in good health 64 days after the valve replacement. PMID- 2266296 TI - [Treatment of postoperative osteomyelitis using an omental pedicle flap]. AB - We described two patients with postoperative sternal osteomyelitis with mediastinal abscess who were successfully treated by omentopexy. One was a 15 year-old boy. Five days after accessory pathway division for Wolff-Parkinson White syndrome, he was diagnosed as having sternal osteomyelitis. Cultures of the exudate yielded staphylococcus epidermidis. Closed continuous irrigation with diluted povidone-iodine was not effective. After open drainage, omentopexy with an omental pedicle flap was performed. Postoperatively, computed tomography showed no abnormal findings in the omental flap and surrounding tissue. The second patient was a 33-year-old man. Re-aortic valve replacement for aortic regurgitation was performed. Eleven days after the operation, he was diagnosed as having postoperative sternal osteomyelitis. Cultures of the drainage fluid yielded staphylococcus epidermidis. Continuous closed irrigation with povidone iodine was ineffective. Thus, the wound was opened and omentopexy with an omental pedicle flap was performed. The postoperative course was uneventful. Computed tomography showed no residual abscess or recurrent inflammation. We conclude that the omentopexy is useful in the treatment of postoperative sternal osteomyelitis. PMID- 2266297 TI - [The law of the orthopaedic medicine]. PMID- 2266298 TI - [Diagnosis and treatment of the slipped capital femoral epiphysis]. PMID- 2266299 TI - [Fracture of the coracoid process: its classification and pathomechanism]. AB - Twenty-eight cases of fractures of the coracoid process were assessed regarding general characteristics, causes of injury, regions of contused wound, fracture types and complications. From the results of the assessment, the fractures were roughly divided into five types: type I; apical, type II; middle, type III; basal, type IV; intraarticular (including upper 1/3-1/4 of the glenoid cavity), and type V; others. Subtypes A and B were present in type III and IV. From the specifics of the contusions and complicated osseous-articular injuries around the shoulder, the mechanisms of injury in each type may be suggests as follows: type I and II; tractive force of attached muscular tendons, type III and IV; shearing force acting between the scapula shifting inward due to blow from the lateral aspect of the shoulder and the clavicle countering this movement, and type V; unspecified. The main cause of fractures of the superior scapular margin was considered to be the tractive force of the superior transverse scapular ligament, because almost all cases of subtype A were complicated with them. For the benefit of the clinical use, they should be classified into two groups: group A; without loss of connection between scapula and clavicle (mainly types I and II), and group B; with loss of the same (majority of types III and IV). PMID- 2266300 TI - [Plastic, partial meniscectomy for the discoid meniscus in children]. AB - Plastic, partial meniscectomy which preserves the marginal part of meniscal cartilage was carried out in our hospital for children with symptomatic lateral discoid meniscus. The post-operative results were good in almost all patients at the follow-up evaluation. We will report on the operative techniques and the post operative evaluation of these cases. From June 1982 to December 1989, 34 discoid lateral menisci in 27 children under the age of 15 years were operated on Itabashi Hospital of Nihon University. After recognition of discoid meniscus with arthroscopy, plastic, partial meniscectomy was carried out via a small transverse skin incision, forming the edge of a normal meniscus. About 2/3 of the central part of a discoid meniscus was resected, leaving about 1.0 cm of its marginal part. The average duration of follow-up was 5 years 4 months. The post-operative results were rated on the basis of the JOA Score for Meniscus Injuries and for the present series stood at 92.9 points. Among these 27 children, 17 had been injured during sports activities and all of them returned to their previous activities except three. Radiologically, mild osteoarthritic changes were noted in only a few cases during the follow-up period. It was concluded that plastic, partial meniscectomy was one of the variable procedures in the treatment of symptomatic discoid meniscus in children. PMID- 2266301 TI - [Purification and characterization of a growth factor from human bone matrix]. AB - A growth factor was purified from human bone matrix by extraction with EDTA, acetone treatment, gel filtration column chromatography, ion exchange column chromatography, and reversed-phase HPLC. Purified protein migrated as a single band to an area with a molecular weight of about 6,000 on SDS-polyacrylamide gel. The purified protein stimulated dose dependent osteoblast proliferation. The sequence of the first 30 N-terminal amino acids of the protein was identical to that of the human insulin-like growth factor-II (IGF-II). MC3T3-E1 cells reacted immunocytochemically to the monoclonal antibody against IGF-II. The culture medium of MC3T3-E1 cells contained immunoreactive IGF-II, which was measured by an enzyme immunoassay. These results indicate that IGF-II is contained in bone matrix, is effective in osteoblast proliferation, produced by the osteoblasts, and secreted from the osteoblasts. Taken together, these results show that IGF-II is present as a local growth factor in the bone system, playing an important role in bone formation following bone resorption. PMID- 2266302 TI - [Experimental study on radial ray deficiency in rat]. AB - Radial ray deficiency were induced in WKAH/Hkm rat fetuses by maternal administration of myleran on either day 10.0, 10.5, or 11.0 of pregnancy. In radial ray deficiency, the severity of absence of the fingers was classified into three types and the degree of radial arrest was classified into four types. The degree of radial arrest was closely related to the severity of absence of the fingers. The greater the dose of myleran was given, the more severe was the radial arrest. As for the soft tissue, the more radial the muscular, nervous and vascular systems were located, the more they were severely affected. The degree of dysplasia of muscular, nervous, and arterial systems depended on the status of dysplasia of the radius. The skeletal and soft tissue anomalies in rats were the same as those in human beings, suggesting that exposure to some environmental factors at a sensitive period of embryogenesis may cause radial deficiency in humans. The critical period for radial ray deficiency is one day later than that for ulnar deficiency in rats, which may contribute to the greater frequency of radial deficiency than ulnar deficiency in humans. It was suggested that the difference of the susceptibility to the environmental factors may determine the phenotype of longitudinal ray deficiencies in embryogenesis. PMID- 2266303 TI - Mast cells in fracture healing: an experimental study using rat model. AB - To investigate the role of mast cells in wound healing process, the time course of appearance and distribution of mast cells were examined during fracture healing in rats. In the early phase of fracture healing, mast cells appeared in the original marrow adjacent to the internal callus. In later phases, mast cells appeared in the newly formed marrow in the external callus. In the external callus the number of mast cells reached a peak at around 5 weeks after fracture when remodeling was progressing. At this phase, the number of mast cells in the convex side of the fracture was significantly greater than that in the concave side. These results suggest that mast cells promote bone resorption, especially during remodeling of callus formed at the fractured site. PMID- 2266304 TI - [Experimental study on the etiology of pathogenesis of acetabular dysplasia in congenital dislocation of the hip]. AB - In order to investigate the etiology of pathogenesis of congenital hip dislocation and acetabular dysplasia, experiments using fetuses of pregnant rabbits were conducted. The following findings were obtained. (1) Dislocation occurred in approximately 40% of total animals used. The earliest dislocation was seen 2 days after birth. (2) The hip dislocation could be relatively and easily generated by exogenous factors during the perinatal period, even without such primary cause, as hip joint dysplasia. The acetabular dysplasia could be generated secondarily to dislocation. (3) There was a difference in the cause of acetabular dysplasia between areas of the acetabulum with and without load. (4) The acetabular depth growth in the dislocated hip was more seriously impaired than the longitudinal and transverse diameters of the acetabular entrance. These results have indicated that endochondral ossification of the epiphyseal cartilage of the acetabulum in the dislocated hip was more markedly impaired than that of Y epiphyseal cartilage. PMID- 2266305 TI - [Natural history and treatment of osteoarthrosis of the hip]. PMID- 2266306 TI - [Diagnosis and treatments of instability of the patellofemoral joint]. PMID- 2266307 TI - Surgical treatment of vertigo. PMID- 2266308 TI - Quelprud's nodule: a post-auricular cartilaginous nodule. AB - A number of minor variations to the configuration of the external ear are well recognized. This paper brings attention to one entity which is characterized by a small cartilaginous nodule or prominence arising from the posterior surface of the pinna and which we have named Quelprud's nodule. A prospective clinical survey of 208 patients attending an ENT clinic revealed that nearly one-third of the population studied possess this nodule. There was an equal sex incidence. The Quelprud's nodule was identified within families in a distribution which suggests an autosomal dominant inheritance with variable expressivity. PMID- 2266309 TI - Conservative management of epistaxis. AB - A retrospective study to assess the clinical usefulness of non-surgical management of epistaxis was performed on 340 patients requiring hospitalisation at the ENT Department of La Paz Hospital (Madrid). The previous history, type of management, hospitalisation time, and volume of transfusion were considered. Nasal packing was employed in 94.1 per cent of the patients. Most patients (82.9 per cent) were hospitalised less than seven days, and 84.1 per cent of the patients required no transfusion. There was one death. This study supports the clinical usefulness of conservative management in the treatment of patients with epistaxis. PMID- 2266310 TI - Uses and complications of uvulopalatopharyngoplasty. AB - Uvulopalatopharygoplasty has become widely performed for chronic snoring and for cases of obstructive sleep apnoea. Unfortunately this operation is not without morbidity and complications. We report our results of a prospective series of 50 patients undergoing uvulopalatopharyngoplasty with a minimum follow-up of one year. Snoring was abolished in 18 (36 per cent) and substantially reduced in the remainder. Obstructive sleep apnoea syndrome, identified in 11 patients pre operatively, was reduced in severity in all but three. Troublesome complications were seen in 18 (36 per cent) patients, namely intermittent velopharyngeal incompetence in five (10 per cent), pharyngeal dryness in 11 (22 per cent) and loss of taste in five (10 per cent). One patient had nasopharyngeal stenosis requiring correction. A cautious approach to this operation is required with rigorous case selection. The importance of full assessment and careful follow-up should not be underestimated. PMID- 2266311 TI - Vocal fold sulcus. AB - Vocal fold sulcus is a cause of dysphonia which has not been recognized until recently. Awareness of its existence combined with use of laryngostroboscopy would enhance the management of this group of patients. Five such cases were treated initially by voice therapy and subsequently combined with microlaryngeal Teflon injections of the vocal cord. Representative photomicrographs and the end results of treatment are presented. A good voice, subjectively and objectively, was obtained in three patients, with satisfactory improvement in the other two. PMID- 2266312 TI - Vertical partial laryngectomy on demand. AB - The author proposes the term 'vertical partial laryngectomy on demand' for all modifications of vertical laryngectomies (frontal, frontolateral, vertical and hemilaryngectomy). This term includes two conditions: the first is complete oncological removal of the tumour (proven by histological examination and with the use of magnification or the operating microscope during the operation); secondly, reconstruction of the laryngeal defect by various procedures. The author uses the sternohyoid fascia in vertical and frontolateral partial laryngectomies. From 120 operated cases, a five-year survival rate of 81 per cent was achieved. The fascia showed resistance to post-operative complications and irradiation. PMID- 2266313 TI - Tracheostomy closure in restrictive respiratory insufficiency. AB - A retrospective study is presented of 31 patients who required ventilatory support via a tracheostomy for periods of one month to 27 years whilst in a tertiary referral centre for the care of patients with restrictive respiratory insufficiency. All patients underwent closure of a long-standing tracheostomy. Post-operative follow-up periods of up to 16 years are documented. The indications for and the complications of tracheostomy closure in patients with severe chronic restrictive respiratory insufficiency requiring long-term respiratory support are discussed. It is concluded that the benefits of operative tracheostomy closure outweigh the disadvantages in this unusual type of patient. PMID- 2266314 TI - Use of EMLA cream as an analgesic in the management of painful otitis externa. AB - A new application of EMLA cream is described. Relief of pain in otitis externa is difficult and systemic analgesics for this localized condition are often ineffective. Meticulous cleaning of the external auditory meatus is an essential step in the treatment. EMLA cream is an effective analgesic which can be used to relieve pain and anaesthetize the external auditory meatus to allow cleaning in patients with intact tympanic membranes. PMID- 2266315 TI - Ulcerative colitis and giant cell arteritis associated with sensorineural deafness. AB - Sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis. A patient is described in whom acute sensorineural deafness occurred in association with episcleritis, ulcerative colitis and clinical features suggesting giant cell arteritis. PMID- 2266316 TI - Leiomyoma of the nasal septum. PMID- 2266317 TI - Early inappropriate secretion of antidiuretic hormone after trans-sphenoidal pituitary adenomectomy. AB - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a rare but life-threatening complication of trans-sphenoidal pituitary adenomectomy. It has previously only been described as a late phenomenon. We report an early presentation within the first week. The pathophysiology, clinical features and treatment are discussed. PMID- 2266318 TI - Marijuana smoking as a possible cause of tongue carcinoma in young patients. AB - A case of T1N0M0 carcinoma of the tongue in a male 23-year-old 'regular' marijuana smoker is described. Hemiglossectomy and complete bilateral neck dissection were carried out. No post-operative radiotherapy was given as the resection margins were histologically negative. The tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed, but after three months, neck disease was still evident. The case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours. Resection of the primary lesion has to be as wide as possible even in T1 cases, due to the aggressive biological behaviour of such tumours in young subjects. PMID- 2266319 TI - Pharyngeal adenocarcinoma with intestinal features. AB - A high grade adenocarcinoma arising primarily in the pharynx of a 67-year-old man is presented. A CT-scan revealed a tumour mass growing in the pharynx, largely affecting parapharyngeal soft tissues. Lymph node metastases were found at clinical presentation. Both morphological and immunohistochemical studies displayed similar features to those of intestinal origin. To our knowledge, no previous examples of such neoplasm have been reported at this site. Its possible histogenetical origin is discussed. PMID- 2266320 TI - Cartilaginous metaplasia of the epiglottis. AB - Metaplastic elastic cartilaginous tissue has been described in the vocal cord, vestibular fold and ventricle of the larynx. This report documents a case in which cartilaginous metaplasia developed in the soft tissue of the epiglottis following an episode of epiglottitis. PMID- 2266321 TI - Fourth branchial pouch anomaly. AB - We present an extremely rare case of fourth branchial fistula in a 23-year-old male. The characteristic clinical feature was a recurrent left lower neck abscess which did not respond to appropriate medical and surgical therapy. Radiography and a computed tomographic scan with contrast material revealed a fistula running from the apex of the left pyriform sinus (internal opening) to the left lower neck abscess. The fistula tract was excised surgically. Histological examination of the excised fistula revealed a squamous epithelial lining and subepithelial lymphoid tissue. This pyriform sinus fistula is thought to be of fourth pharyngeal pouch origin, because of its surgical aspects and the histological findings of the excised fistula. PMID- 2266322 TI - Cystic hygroma: massive recurrence in adult life. AB - Cystic hygroma is considered a disease of childhood. It may appear for the first time in adult life but recurrence by that stage is rare and may present difficulties in diagnosis due to previous treatment. The authors present a case where early pharmacological intervention may have prevented a potentially life threatening situation. The world literature is also reviewed. PMID- 2266323 TI - Patenting medical technology. PMID- 2266324 TI - Informed consent does not mean rational consent. Cognitive limitations on decision-making. PMID- 2266326 TI - Structured spreadsheet modeling in medical decision making and research. AB - The construction, evaluation, implementation, and use of models representing various algorithms, strategies, methods, theories etc. based on the analysis of great amounts of data are necessary in both Medical Research and Decision Making (MR/DM). Performing such tasks manually is not only time consuming and tedious, but also very error-prone. The appearance of a computer with its ability to store and process information has opened an opportunity to facilitate enormously and improve activities. However, the effective use of computers is limited by difficulties accompanying noncomputer specialists like doctors, nurses, and other medical staff in learning and using conventional programming languages, tools, and techniques. In this paper we present Structured Spreadsheet Modeling as a possible solution, and show that it is applicable in the MR/DM field on a concrete basis. PMID- 2266325 TI - Physician specialty advertising. The tendency to deceive? PMID- 2266327 TI - A personal computer-based maintenance management expert system for hospitals. AB - In this paper a Maintenance Management Expert System (MMES) is developed. This system is suitable for hospitals as well as for manufacturing organizations. This expert system consists of five sections. These are work order management, equipment management, craftsmen management, material and supply control, and monitoring of maintenance activities. In addition the MMES provides several reports that can be utilized for improving maintenance effectiveness. PMID- 2266328 TI - Medical application of vest pocket computers. PMID- 2266329 TI - Smart cards in medicine. PMID- 2266330 TI - Health cards--the move toward standards. PMID- 2266331 TI - The Exeter Care Card: a CP8-based global health care record for the United Kingdom's National Health Service. PMID- 2266332 TI - The optical memory card: a portable medical record. PMID- 2266333 TI - Press release: European community to use Smart Patient Cards. PMID- 2266335 TI - Jogging--for a healthy heart and worn-out hips? PMID- 2266334 TI - Sensory feedback and the impaired motor system. AB - A group design study was carried out using regulated feedback to enhance functional recovery in stroke patients. Patients trained on three computerized tasks aimed at improving guided limb motion in the hemiplegic arm. The therapeutic group was able to make use of the sensory feedback to outperform the control group in each of the three tasks. The therapeutic group also showed an adaptation of the improved performance on the three tasks. Further investigation is required to demonstrate that such sensory feedback training results in a corresponding improvement in activities of daily living skills. PMID- 2266337 TI - Long-term follow-up in isolated ventricular septal defect considered too small to warrant operation. AB - An isolated ventricular septal defect (VSD) was diagnosed in 70 patients (39 men and 31 women, mean age 29 years, range 10-64 years). Surgery was judged unnecessary. The follow-up period was at least 10 years, or until death or 31 December 1988, comprising a mean duration of 21 (range 6-29) years. The mortality was 11/69 (one lost to follow-up), and was not significantly higher than in a matched 'normal' group. Six deaths were cardiac, four of which could probably be related to the VSD. The follow-up study revealed that: (1) 14 (22%) subjects had major, VSD-related complications, and cardiac surgery was indicated in eight patients; (2) six (10%) had minor complications. By the end of 1988, 24% of subjects had significant dyspnoea, 22% had chest pain and 19% used cardioactive drugs. Only 33% were receiving regular cardiac control in a hospital. Thus unoperated adults with a small VSD should be monitored closely, since this condition is far from benign. PMID- 2266336 TI - Extracerebral manifestations in migraine. A peptidergic involvement? PMID- 2266338 TI - Fat distribution and steroid hormones in women with alcohol abuse. AB - Anthropometric, hormonal and liver function parameters were examined in 18 premenopausal women with a history of early alcohol abuse, and compared with the data for randomly selected controls of the same age. The alcoholic women showed slightly elevated levels of transaminases, but no clinical or laboratory signs of advanced liver damage. These women were characterized by an increased waist-to hip ratio, due to enlarged waist circumference. Several endocrine abnormalities were found, including irregular or absent menses as well as low oestrogen, progesterone and delta-4-androstendione levels. The concentration of free testosterone was high and that of sex-hormone-binding globulin was low. These data suggest abdominal distribution of body fat, as well as hyperandrogenicity in alcoholic, premenopausal women. It is postulated that the endocrine abnormalities might be responsible for the abdominal fat distribution. PMID- 2266339 TI - Lipoprotein-related coronary risk factors in patients with angiographically defined coronary artery disease: relation to number of stenosed arteries. AB - To determine whether an index estimating antagonism between low density lipoprotein (LDL) and high density lipoprotein (HDL) would improve separation between groups with and without coronary artherosclerosis, patients undergoing coronary catheterization (35 women and 99 men) were analysed for total cholesterol (TC), HDL cholesterol (HDLc), apolipoprotein A (apo A) and apolipoprotein B (apo B). The subjects were categorized as groups 0, 1, 2 or 3 according to the number of stenosed arteries (greater than 75% areal stenosis). Thirty of the patients showed no significant coronary atherosclerosis (group 0). Serum apo B and TC concentrations were directly related to the number of stenosed vessels, whereas the concentrations of apo A and HDLc were negatively correlated with the number of stenosed arteries. An 'atherogenic Index' (ATH index) calculated as the product of serum concentrations of apo B, and TC minus HDLc divided by the product of apo A and HDLc, proved more satisfactory than individual lipoprotein components for discrimination between subjects with and without stenosis. Accordingly, identification of coronary groups may be improved by using the ATH index. PMID- 2266340 TI - Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins. AB - In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure. Blood pressure was effectively reduced in all groups. Patients on hydrochlorothiazide showed a significant increase (P less than 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment. A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P less than 0.05) of treatment in patients on metoprolol. In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P less than 0.001) and 6 months (P less than 0.05), triglycerides increased after 6 (P less than 0.01) and 12 months (P less than 0.01), and LDL-C increased after 3 (P less than 0.05), 6 (P less than 0.001) and 12 months (P less than 0.01) of treatment, respectively. In 61% of the patients, three or more lipid parameters were affected during the study period. We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease. PMID- 2266341 TI - Wives of coronary high-risk men--are they also at higher risk? The Tromso Heart Study. AB - Blood lipids, blood pressure, body mass index (BMI), smoking, dietary and exercise habits were studied in 911 wives of men with high risk for coronary heart disease (CHD). Following the 1979/80 Tromso Survey, 1373 men, aged 30-54 years, were identified as having high risk for CHD (HDL-cholesterol/total cholesterol less than or equal to 17.6% and/or total cholesterol greater than or equal to 7.86 mmol l-1). Of the 1373 men, 911 individuals had wives who also attended the screening. These wives were compared to age-matched, married women in the general population. A significantly higher total cholesterol level (5.98 mmol l-1 vs. 5.78 mmol l-1), lower HDL-cholesterol/total cholesterol (30.01% vs. 31.58%), higher BMI and higher coronary risk score (4.55 vs. 3.82) was found among the wives of the high-risk men. Furthermore, a higher proportion of these individuals were daily cigarette smokers (47.3% vs. 42.1%), and had received fewer years of education. They also had more dietary habits associated with increased risk of CHD than other married women in the general population. Our findings support the hypothesis that members of the same household as a person with increased risk for CHD also have increased risk. This is most probably due to shared lifestyle. PMID- 2266343 TI - Metabolite and hormonal profiles in heat stroke patients at Mecca pilgrimage. AB - Sera obtained during the Hajj seasons of 1985, 1986, 1987 and 1988 from 125 heat stroke patients were collected and subjected to chemical analysis which included determination of glucose, lactate, cholesterol, and triglycerides, as well as assay of T3, T4, TSH and cortisol. Hyperglycaemia and lactic acidaemia were found to be the most frequent metabolic abnormalities. The changes in cholesterol did not exhibit a specific pattern. Triglycerides were significantly elevated in only 6% of patients. Cortisol levels were very significantly elevated in precooled patients. Although the mean T3 levels remained within the normal range, the mean concentration on admission was significantly higher than the post-cooling mean. TSH and T4 levels did not show significant changes. PMID- 2266342 TI - Verapamil increases serum alkaline phosphatase in hypertensive patients. AB - In rats, verapamil decreases intestinal absorption of calcium, increases serum parathyroid hormone (PTH), and induces osteopenia. In this prospective study, verapamil 80-120 mg three times daily was given for 2 months to 20 patients with hypertension, and the effects on calcium homeostasis were recorded. This dose of verapamil significantly reduced supine systolic and diastolic blood pressure (+/- SD) from 158/100 +/- 9/8 mmHg to 146/89 +/- 14/8 mmHg (P = 0.001). Serum alkaline phosphatase (ALP) increased significantly from 2.77 +/- 1.06 mu kat l-1 to 3.19 +/- 1.22 mu kat l-1 (P = 0.004), and isoenzymes of ALP of skeletal origin appeared after verapamil treatment. The excretion of sodium in the urine increased (Na/creatinine ratio 8.95 +/- 6.01 before and 13.16 +/- 8.26 after verapamil; P = 0.04), while the excretion of calcium, phosphate and potassium was not changed. PTH was slightly increased at the end of verapamil treatment (1.09 +/- 0.54 vs. 0.98 +/- 0.74 microgram l-1; P = 0.07), and s-1,25(OH)2D3 was also somewhat increased (22.3 +/- 14.4 vs. 17.6 +/- 4.9 ng l-1; P = 0.26). Serum Ca was not affected by verapamil (before verapamil 2.43 +/- 0.11 mmol l-1, after verapamil 2.40 +/- 0.12 mmol l-1; P = 0.28). The increase in serum ALP demonstrates that verapamil affects bone cell metabolism in man. This effect could be secondary to the enhancement of PTH secretion. PMID- 2266344 TI - Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria. AB - Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/ 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P. PMID- 2266345 TI - Trimethoprim-sulphamethoxazole-associated blood dyscrasias. Ten years' experience of the Swedish spontaneous reporting system. AB - During the 10-year period 1976-1985, a total of 154 cases of blood dyscrasia were reported in Sweden which were evaluated as having a probable or possible causal relationship with trimethoprim-sulphamethoxazole (T-SM). There were 61 cases of leucopenia (of which 16 had agranulocytosis), 28 cases of thrombocytopenia, and two of non-haemolytic anaemia. There were also 32 cases of bicytopenia and 31 cases of tricytopenia. The median age varied from 38 years in the leucopenia group to 81 years in those with tricytopenia. The overall fatality rate was 17%, ranging from 2% in the group with mild leucopenia to 52% in the group with tricytopenia. In relation to sales and prescription data, the overall incidence of reported T-SM blood dyscrasias was 5.3 per million defined daily doses, and among out-patients the incidence was one case per 18,000 prescriptions. Thus the overall incidence of any blood reaction to T-SM appears to be low. In relation to prescription data, elderly people were overrepresented among the serious reactions. PMID- 2266346 TI - The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid. AB - Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency. PMID- 2266347 TI - Drug related admissions to a cardiology department; frequency and avoidability. AB - Three hundred and sixty-six consecutive patients admitted to a department of cardiology were evaluated for drug events as a cause of admission. The drug events considered were adverse drug reactions (ADR) and dose-related therapeutic failures (DTF). 'Definite' or 'probable' drug events accounted for 15 admissions (4.1%, 95% confidence limits 2.3-6.7%), of which eleven were ADR and four were DTF. With the inclusion of six 'possible' drug events, the rate of drug-related hospitalizations (DRH) was 5.7%. DRHs were characterized by a preponderance of acute admissions and elderly patients. Hypokalaemia (less than 3.5 mM) was observed in 27 (16%) patients receiving diuretics, and could be related to four cases of arrhythmias (two 'probable' and two 'possible' ADR). The average serum potassium level was similar in diuretic treated patients with or without drugs to counteract hypokalaemia, irrespective of the drugs chosen. Among the 15 'definite'/'probable' DRHs, five were considered to be due to an error in prescription, and a further five cases were judged to have been avoidable had appropriate measures been taken by prescribing physicians. A DRH educational intervention programme should primarily deal with non-compliance or with prescription of diuretics or digoxin, since these problems constitute the majority of cases of DRH. No specific group of doctors could be targeted as responsible for DRH, avoidable or not. PMID- 2266348 TI - Glucose tolerance and hyperinsulinaemia in obese women: role of adipose tissue distribution, muscle fibre characteristics and androgens. AB - The separate independent statistical contribution of abdominal distribution of fat, hyperandrogenicity and muscle morphology to glucose intolerance and hyperinsulinaemia was analysed in 88 obese women. In univariate analyses the waist/hip circumference ratio (WHR), body fat and lean body mass were all positively associated, and SHBG levels were negatively associated with insulin and glucose values. Muscle fibre areas were positively correlated with insulin but not with glucose concentrations. Adjustment for other variables did not remove the positive association between WHR and fasting insulin and glucose concentrations. SHBG, free testosterone and type IIb fibre areas were, however, significant confounding factors in the relationship between WHR and summed insulin and glucose concentrations. We conclude that fat distribution in obese women is associated with fasting hyperglycaemia and hyperinsulinaemia, independently of androgens and muscle fibre morphology, but that reduced SHBG concentrations and increased type IIb fibre areas may partly explain increased glucose and insulin responses to an oral glucose load in abdominally obese women. PMID- 2266350 TI - Skeletal scintigraphy in coeliac disease. AB - A patient with undiagnosed, long-standing coeliac disease had multiple hot spots on skeletal scintigraphy, similar to those observed in malignant disease metastatic to the skeleton. A gluten-free diet corrected the pathological laboratory values, and a repeat skeletal scintigram 15 months after the first one was normal. It is important to identify the secondary hyperparathyroidism of coeliac disease as a cause of multiple hot spots in skeletal scintigraphy--the finding resembles malignancy, but is due to a benign, curable condition. PMID- 2266349 TI - Renal reserve filtration capacity before and after kidney donation. AB - Renal reserve filtration capacity (RRFC) was investigated in 20 kidney donors before and within 3 months after uninephrectomy. Glomerular filtration rate (GFR) was measured by the clearance of 125I-iothalamate, and effective renal plasma flow (ERPF) was determined by the clearance of 131I-hippurate. RRFC was tested by infusion of a low dose of dopamine, by intravenous administration of an amino acid solution and, finally, by combined infusion of amino acids and low-dose dopamine. After kidney donation, the median value of the GFR was 65% of its initial value. The median value of the ERPF was 69% of its value before uninephrectomy. The filtration fraction declined significantly from 0.251 to 0.238 (medians; P less than 0.02). Median values for dopamine-induced increases in GFR were 13.8% before and 5.3% after kidney donation (P less than 0.005). Infusion of amino acids led to an increase in GFR of 11.2% before and 9.6% after donation (NS). During combined infusion, the median values for the increases in GFR were 20.0% before and 12.6% after uninephrectomy (P less than 0.02). Median changes in ERPF before and after kidney donation were 33.4 vs. 23.0% during dopamine infusion (P less than 0.005), 10.0 vs. 8.3% during amino acid infusion (NS), and 36.2 vs. 24.3% during the combined infusion of dopamine and amino acids (P less than 0.02). Infusion of dopamine induces a decrease in renal vascular resistance, resulting in a rise in glomerular blood flow. Since RRFC tested by means of dopamine infusion was significantly decreased after kidney donation, it is concluded that glomerular hyperfiltration after kidney donation is at least partially due to a rise in glomerular blood flow. PMID- 2266351 TI - Treatment of severe colitis in Behcet's syndrome with thalidomide (CG-217). AB - A 35-year-old male patient, known in our department since 1979 on account of a severe and complete Behcet's syndrome, was treated with thalidomide (CG-217) as a final pharmacological measure to avoid colectomy during a severe attack of Behcet colitis. Prior to the administration of thalidomide, the patient had been treated for 7 weeks with full parenteral nutrition and high doses of steroids intravenously without a satisfactory effect on the colitis. Treatment with sulphasalazin was unsuccessful because of a decreasing number of platelets on this drug. After a few days on thalidomide, 300 mg given once daily at bedtime, the patient's stools were normalized and without reaction for blood, his oral ulcers and pleural effusion disappeared, and his steroid doses could be reduced. Gradually he was put on oral nutrition again, and his rectal mucosa became normalized. The dose of thalidomide was reduced to 200 mg, and then to 100 mg daily when the patient was discharged from hospital, less than 3 weeks after institution of the drug treatment. After 5 months as an out-patient his condition is still satisfactory and without symptoms of his former disease. Thalidomide has previously been reported to be of value in treatment of Behcet's syndrome, but to my knowledge never with such a dramatic effect on a severe colitis as reported in this case. PMID- 2266352 TI - Gall-bladder perforation after long-term dapsone therapy. AB - A 65-year-old man on maintenance dapsone therapy for dermatitis herpetiformis for 30 years was admitted to hospital with acute abdominal pain and vomiting. Investigations revealed a Heinz body haemolytic anaemia. Worsening symptoms prompted an emergency laparotomy that revealed a perforated gall bladder with pigmented biliary calculi. In previous reviews of the haematological abnormalities associated with dapsone therapy, life-threatening cholecystitis has not been described. PMID- 2266353 TI - Could splenectomy worsen autoimmune manifestations? PMID- 2266354 TI - Alcohol and zinc deficiency: contribution to villous atrophy. PMID- 2266355 TI - Illegitimacy, child abuse and neglect, and cognitive development. AB - This study explored the relationship between illegitimate birth and cognitive development among 513 boys on probation. Prior research has shown that being part of a single-parent household leads to diminished verbal capacities and often puts a child in greater danger of abuse and neglect. Frequent abuse is thought to lead to the enhancement of visual and spatial skills relative to verbal skills through a process of "frozen watchfulness". I hypothesized that illegitimate boys from one-parent homes would have greater verbal-performance discrepancy scores than would boys from other combinations of birth status and family structure. These boys had the lowest verbal IQ and highest performance IQ scores and, hence, the largest discrepancy. These boys also suffered the highest degree of abuse and neglect of all four birth status/family structure combinations studied. PMID- 2266356 TI - Sequence and structure in the concept development of children with emotional and behavioral difficulties. AB - We investigated the order of acquisition of concepts and cognitive processes in children with emotional and behavioral difficulties and the extent to which these children show similarity to ordinary children in sequence and structure of development. Similarity in developmental sequence was strongly supported by scalogram analyses and has clear implications for organizing teaching, but similarity in structure was less clear. Cognitive processes however, and the nature of the children's reasoning were clarified by the method of exploration used. This was particularly fruitful for providing insight into the difficulties children may have. The findings thus contribute to understanding with a view toward furthering concept development in children with emotional and behavioral difficulties. PMID- 2266357 TI - Maternal depressed mood and perceptions of child temperament. AB - Research has suggested that women who experience postpartum depression are subsequently more likely to perceive their preschool-aged children as temperamentally difficult and maladjusted. However, previous studies have not controlled for the effects of concurrent depression levels on maternal ratings of child temperament or evaluated the accuracy of maternal reports. In the present study we assessed maternal and paternal ratings of child temperament 2 years after subjects had participated in a study of postpartum depression. The findings indicate that correlations between postpartum depression and subsequent child temperament ratings were accounted for statistically by concurrent levels of depression. Although fathers' ratings corroborated some aspects of maternal perceptions, levels of parental agreement were only moderately high. Moreover, discrepancies between the parents' reports were significantly associated with maternal depression, indicating that parental disagreement is more likely when the wife is dysphoric. PMID- 2266358 TI - Children's evaluations of morality in the context of peer, teacher-child, and familial relations. AB - The purpose of this study was to investigate how children evaluate moral transgressions (rule violations that do not involve conflicts) and conflicts (stories involving peer, teacher-child, and familial relations) and how children weigh different issues and re-evaluate their decisions after hearing new information about the conflict. Results showed that children at all ages supported decisions by authorities (peer and adult) to ignore social order violations to prevent harm or a failure to share. Decisions to give preference to interpersonal relations were made for issues about harm but not about sharing resources. The findings demonstrate that children give priority to the prevention of harm and a failure to share for some, but not all types of moral conflicts, and that the salience of moral consequences influences their overall evaluation. PMID- 2266359 TI - Risk factors for multiple sclerosis: race or place? PMID- 2266360 TI - The frequency, causes and timing of death within 30 days of a first stroke: the Oxfordshire Community Stroke Project. AB - In a prospective, community-based study of 675 consecutive patients with a first ever stroke, of whom over 90% had computed tomography (CT) and/or necropsy examinations, 129 deaths occurred within 30 days of the onset of symptoms, a case fatality rate (CFR) of 19%. The 30 day CFR for patients with cerebral infarction was 10% (57 of 545, for primary intracerebral haemorrhage 52% (34 of 66), for subarachnoid haemorrhage 45% (15 of 33) and for those of uncertain pathological type 74% (23 of 31). The CFR for patients who had been functionally dependent pre stroke was 33% compared with 17% for those who had been independent pre-stroke. The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater (1.8, 95% confidence interval 0 to 4.3). There was a significant trend for CFR to increase with age (Chi square for trend = 4.0, p less than 0.05). This relationship was found in those patients who had been functionally independent prestroke (Chi square for trend = 7.9, p less than 0.005) but not in those who had been dependent pre-stroke (Chi square for trend = 0.5, NS). The pattern of increasing CFR with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infarction (Chi square for trend = 8.6, p less than 0.005). The age adjusted relative risk of death for patients with cerebral infarction who had been functionally dependent pre-stroke was 2.2 (95% confidence interval 1.2 to 4.1). Fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke. Patients with primary intracerebral or subarachnoid haemorrhages were significantly more likely to die in this way than those with cerebral infarction (relative risk 4.1; 95% confidence interval 3.4-4.9) and 56% of such deaths occurred within 72 hours of onset. In patients with cerebral infarction, 51% of deaths were due to complications of immobility (for example, pneumonia, pulmonary embolism) and these were more likely to occur after the first week. These findings have implications for clinical practice and the planning of clinical trials. PMID- 2266361 TI - The natural history of non-arteritic anterior ischaemic optic neuropathy. AB - Seventy one patients with non-arteritic anterior ischaemic optic neuropathy were studied retrospectively. Sixty three (89%) were followed to the end of the study or death, mean follow up time was 5.3 years. Whilst twenty (28%) had diabetes or hypertension, in thirty nine (55%) no predisposing condition was identified. In those who had monocular disease at presentation (68), subsequent involvement of the second eye occurred in seventeen (25%), seven within the first year. Nineteen patients died within the study period. Of these, nine died from myocardial infarction and four from cerebrovascular disease. This is a significant increase above figures calculated from the Office of Population Census and Surveys (p less than 0.001 for all causes, p less than 0.002 for myocardial infarction and cerebrovascular disease). Such an increase in mortality has not been previously reported, and implies that this condition carries a more sinister systemic prognosis than is frequently supposed. PMID- 2266362 TI - Syndromes of transient amnesia: towards a classification. A study of 153 cases. AB - Of 153 patients presenting with acute transient amnesia, 114 fulfilled the proposed strict diagnostic criteria for transient global amnesia (TGA). The prognosis of this group was excellent with the exception of a small subgroup (7%), largely identifiable because of atypically brief or recurrent attacks, who developed epilepsy of temporal lobe type on follow up. Computerised tomography (CT) scans performed on 95 patients were normal, evidence for covert alcoholism was lacking and there was a familial incidence of approximately 2%. By contrast, the group of 39 patients who did not meet the criteria for TGA had a significantly worse prognosis with a high incidence of major vascular events. The groups could not be distinguished on the basis of behavioural characteristics during the attack. The following classification was proposed: 1) pure TGA- attacks fulfilling the strict criteria, and of more than one hour in duration which do not require detailed investigation, 2) probable epileptic amnesia- attacks of less than an hour or rapidly recurrent, 3) probable transient ischaemic amnesia, a minority of cases with additional focal neurological deficits during the attack. PMID- 2266363 TI - Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction. AB - We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction. Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change. The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01). Nicardipine (Ni) had no effect on SEP components in the intact hemispheres. Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs. Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP. These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone. PMID- 2266365 TI - Platelet monoamine oxidase B activity in parkinsonian patients. AB - Monoamine oxidase B (MAO B) plays a pivotal role in N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) induced Parkinsonism. An increased MAO B activity in platelets of patients with idiopathic Parkinson's disease (PD) is reported in this study. The possibility that high MAO B activity may represent a trait of vulnerability for PD by enhancing the neurotoxic effects of environmental compounds is discussed. PMID- 2266364 TI - Insulin protects cognitive function in experimental stroke. AB - There is evidence from in vitro systems that the extent of neuronal loss in acute central nervous system ischaemia can be reduced by manoeuvres which restrict availability of glucose to the ischaemic area. Experiments were designed to test whether hypoglycaemia induced with insulin is associated with improved behavioural outcome in a recovery model of stroke. Rats learned a maze task as a test of working memory, believed to be subserved by the hippocampus, and then had a period of cerebral ischaemia, followed by reperfusion. After an interval of 14 days they were tested on the same maze, where lesioned animals had very significant (p less than 0.0001) impairment of working memory, whereas lesioned and treated (2.0 u/kg-1 insulin, minimum single plasma glucose value: 3.1 mmol/l 1) animals were indistinguishable from control animals. It is concluded that a striking degree of protection can be obtained with levels of mild hypoglycaemia which may be acceptable and practicable for use in humans. PMID- 2266366 TI - Changes in the basal dendrites of cortical pyramidal cells from alcoholic patients--a quantitative Golgi study. AB - Although a variety of pathological changes have been described in the brains of chronic alcoholic patients, there have been no studies which have addressed the question of alterations in cortical neuronal dendritic arborisation. Loss of neurons from the superior frontal gyrus and shrinkage of neurons from both the superior frontal gyrus and motor cortex has been documented in chronic alcoholic patients; these areas were chosen for this study. Using a modified rapid Golgi technique the basal dendritic arborisation of layer III pyramidal neurons was compared in 15 male alcoholic patients and 15 age-matched male controls. All parameters measuring basal dendritic arborisation were significantly less in the alcoholic cases for both the superior frontal and motor cortices. Changes in the arbor are in the terminal branches, which is consistent with other models of dendritic plasticity. Such changes may explain both permanent and reversible functional deficits in chronic alcoholic patients. PMID- 2266368 TI - Specificity of affective and autonomic symptoms of depression in Parkinson's disease. AB - Previous investigators have suggested that numerous symptoms used to diagnose depression, such as sleep or appetite disturbance, are non-specific in medically ill patients, and alternative diagnostic criteria should be developed. In the study this hypothesis was tested in Parkinson's disease (PD) by comparing patients with PD who reported a depressive mood with patients having PD but without a depressive mood. Depressed patients showed a significantly higher frequency of both autonomic and affective symptoms of depression. Depressed patients with PD reported a significantly higher frequency of worrying, brooding, loss of interest, hopelessness, suicidal tendencies, social withdrawal, self depreciation, ideas of reference, anxiety symptoms, loss of appetite, initial and middle insomnia, and loss of libido when compared with non-depressed patients. No significant between-group differences, however, were observed in the frequency of anergia, motor retardation, and early morning awakening. PMID- 2266367 TI - Temporal movement control in patients with Parkinson's disease. AB - Patients with Parkinson's disease (PD) have been reported to be unable to modify their movement velocity to adapt to changing environmental demands. For example, when movement amplitude is varied, PD patients usually exhibit a nearly constant peak velocity, whereas elderly subjects show an increase of their peak velocity with increased amplitude. The experiment examined the ability of PD patients to vary the duration of their movement (four different percentages of their maximum) under conditions where temporal, but not spatial, control was emphasised. PD patients had longer movement times than control subjects, but were able to vary the duration of their movement with comparable temporal accuracy to that of elderly subjects. For both groups, the agonist EMG activity increased with decreased movement duration. For the PD patients, the number of agonist bursts increased with increased movement duration. PMID- 2266369 TI - Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome. AB - The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome. Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles. The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons. Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations. In contrast cervical motor root stimulation resulted in responses of normal latency and duration. The phasic stretch reflex had a low threshold, short latency and prolonged duration. It is concluded that in Rett syndrome the corticospinal pathway is intact. The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways. PMID- 2266370 TI - Motor units in incomplete spinal cord injury: electrical activity, contractile properties and the effects of biofeedback. AB - The electrical and contractile properties of hand muscles in a selected population of quadriplegic subjects were studied intensively before and after EMG biofeedback. Spontaneously active motor units and units that could only be slowly and weakly activated were observed in these subjects, in addition to units that were voluntarily activated normally. This suggests a considerable overlap of surviving motor neurons to a single muscle that are below, near or above the level of a lesion. Despite the common occurrence of polyphasic potentials and other signs of neuromuscular reinnervation, the average twitch tension of single motor units in hand muscles of quadriplegic subjects was not significantly different from that in control subjects. Nor did it increase after biofeedback training that typically increased the peak surface EMG by a factor of 2-5 times. The percentage of spontaneously active units was also constant. The surface EMG may be increased during biofeedback by using higher firing rates in motor units that can already be activated, rather than by recruiting previously unavailable motor units. PMID- 2266371 TI - Visual evoked potential monitoring of optic nerve function during surgery. AB - A study was made with intra-operative flash--visual evoked potentials (VEP) monitored using a fibre-optic/contact lens photo stimulator in 57 patients undergoing intra-orbital surgical procedures with potential risk to the optic nerve. The VEPs recorded under enflurane and nitrous oxide anaesthesia did not differ significantly in latency or amplitude from the pre-operative recordings. Transient abolition of the VEP was seen under many circumstances and did not correlate with the outcome of surgery, but absence of a previously normal VEP for more than four minutes during surgical manipulation within the orbit did show a correlation with post operative impairment of vision. The technique provides early warning to the surgeon of threats to the integrity of the optic nerve. PMID- 2266372 TI - Determination of ventricular fluid outflow resistance in patients with ventriculomegaly. AB - Resorption of the ventricular fluid was studied by measuring ventricular fluid outflow resistance during steady state 1.5 and 5.0 ml/min infusions in 26 patients with substantial enlargement of the supratentorial ventricular system. This test may avoid unnecessary use of shunts, but a shunt could be introduced during the same procedure. PMID- 2266373 TI - Multiple sclerosis in Australia and New Zealand: are the determinants genetic or environmental? AB - The prevalence of multiple sclerosis (MS) has been recently reported from nine regions of Australia and New Zealand. There is a marked variation of prevalence with latitude. MS is seven times more common in southern New Zealand than in tropical Queensland. On current evidence, it is suggested that in both countries this variation is predominantly due to environmental rather than genetic factors. PMID- 2266374 TI - Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies. AB - Multiple sclerosis (MS) is very uncommon among ethnic Asians in the Indian subcontinent, among Asians and Africans resident in the New Commonwealth countries of Africa and in the West Indies. It is also very uncommon among those who have migrated to England from those countries. In contrast, the children born in the United Kingdom of Asian, African and West Indian immigrants have, in the age groups available for study, a high prevalence of MS of a similar order to that occurring in the general population of England. PMID- 2266375 TI - Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy. AB - Increased pupillary light reflex latencies were found more often than a reduced darkness pupil size in diabetic patients with and without abnormal cardiovascular reflexes. This finding suggests that parasympathetic pupillary dysfunction precedes sympathetic pupillary denervation in diabetic autonomic neuropathy. PMID- 2266377 TI - Fulminant monophasic multiple sclerosis, Marburg's type. AB - The clinical, neuroradiological and necropsy findings are described in a 49 year old woman with long-standing idiopathic pulmonary haemosiderosis and acute monophasic multiple sclerosis (Marburg's type). Progression of the demyelinating process produced blindness and paraplegia over three weeks. At five weeks, magnetic reasonance imaging (MRI) studies showed lesions in the pons and left occipital lobe. The patient died 10 weeks after onset of symptoms. Necropsy examination revealed acute plaques in the optic chiasm, and the white matter around the lateral and fourth ventricle and spinal cord. Similarities between this and previously described cases of Marburg's disease are discussed. PMID- 2266376 TI - Neuropsychological profile linked to low dopamine: in Alzheimer's disease, major depression, and Parkinson's disease. AB - A distinct pattern of neuropsychological deficits was associated with low homovanillic acid (HVA) in the cerebrospinal fluid of 21 patients with: Alzheimer's disease (9), Parkinson's disease (8) and major depressive disorders (4). Regardless of clinical diagnosis, patients with low HVA were slower on a test of efficiency of processing timed information, and showed greater benefit from semantic structure on a verbal fluency task than patients with high HVA. However, low HVA subjects were not significantly impaired on confrontation naming (Boston Naming Test). Across three diagnostic groups, patients with lower HVA also tended to have more extrapyramidal motor signs and were significantly more depressed. These results demonstrate a significant relationship between specific neuro-behavioural deficits and dopaminergic activity which cuts across traditional diagnostic categories. PMID- 2266378 TI - Unilateral proptosis secondary to partially thrombosed giant carotid ophthalmic artery aneurysm. PMID- 2266379 TI - Pituitary abscess with recurrent aseptic meningitis. PMID- 2266380 TI - Transient global amnesia following ingestion of chloroquine. PMID- 2266381 TI - Iliac aneurysms. PMID- 2266382 TI - "Disconnected" integral ventriculo-peritoneal shunt systems. PMID- 2266383 TI - Radioimmunoconjugates. Targeting disease for diagnosis and treatment. PMID- 2266384 TI - A prospective comparison of rubidium-82 PET and thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease. AB - The purpose of the present study is to prospectively compare myocardial perfusion imaging with rubidium-82 (82Rb) by positron emission tomography (PET) with thallium-201 (201Tl) imaging by single-photon emission tomography (SPECT) by recording both studies with a single dipyridamole handgrip stress, and reading both sets of images with the same display technique. In a series of 202 patients with previous coronary arteriography, the sensitivity, specificity, and accuracy of 82Rb PET were 93%, 78%, and 90% and for 201Tl SPECT 76%, 80%, and 77%, respectively. When 70 patients with previous therapeutic interventions were excluded, the remaining 132 patients showed a sensitivity, specificity, and accuracy of 95%, 82% and 92% for 82Rb PET and 79%, 76%, and 78% for 201Tl SPECT. The improved contrast resolution of PET resulted in markedly superior images and a more confident identification of defects. PMID- 2266385 TI - Planar, SPECT, PET: the quest to predict the unpredictable? PMID- 2266386 TI - Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis. AB - Assessment of gallium-67 (67Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis. A distinctive intrathoracic lymph node 67Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%). Symmetrical lacrimal gland and parotid gland 67Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients. A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients. The presence of either of these patterns was particularly prevalent in roentgen Stages I (80%) or II (74%). We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures. PMID- 2266387 TI - Gallbladder perforation: correlation of cholescintigraphic and sonographic findings with the Niemeier classification. AB - We retrospectively analyzed the cholescintigrams and sonograms of 36 consecutive patients with gallbladder perforation to (a) determine the sensitivity of each for the preoperative detection of gallbladder perforation and (b) correlate the findings with the modified Niemeier classification. Cholescintigraphic criteria of perforation (free spill, pericholecystic hepatic activity, and scintigraphic gallstone ileus sign) were detected in 14 of 28 (50%) cases, while sonographic criteria of perforation (pericholecystic fluid or pneumobilia with gallstones) were present in 18% (4 of 22) of patients (p less than 0.05). Cholescintigraphic patterns of perforation associated with the Niemeier classification were: Type I (acute free perforation), 3 of 7 scans demonstrated free spill; Type II (subacute pericholecystic abscess), 9 of 19 scans showed pericholecystic activity; and Type III (chronic cholecystoenteric fistula), 1 of 3 scans showed a scintigraphic gallstone ileus. Thus, although cholescintigraphy appears superior to sonography, both modalities are relatively insensitive for the detection of gallbladder perforation. PMID- 2266388 TI - Differential diagnosis of lung tumor with positron emission tomography: a prospective study. AB - To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors. PMID- 2266389 TI - The clinical utility of radionuclide ventriculography in cardiac transplantation. AB - To assess ventricular function in patients who have undergone cardiac transplantation, 247 radionuclide ventriculograms were performed on 94 patients. During the first three days after transplantation, 19% demonstrated left ventricular dysfunction and 41% showed isolated right ventricular dysfunction. In 95 cases, radionuclide ventriculography was performed within 24 hr of myocardial biopsy. A reduction in left ventricular ejection fraction to less than 50% was significantly more common with moderate-severe rejection than with mild rejection. In six instances in which there was discordance between ventriculography and biopsy, radionuclide ventriculography proved particularly useful: three cases showed severe left ventricular dysfunction despite only mild rejection by biopsy, and three cases with ventricular dysfunction from rejection were missed by the initial biopsy. Thus, radionuclide ventriculography can provide functional data in transplant patients that is complementary to myocardial biopsies since biopsy grade is a poor predictor of left ventricular function and biopsy can miss significant rejection. PMID- 2266391 TI - Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection. AB - Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied with combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure. PMID- 2266390 TI - SPECT quantitation of iodine-131 concentration in phantoms and human tumors. AB - The validity of SPECT measurement of iodine-131 (131I) concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations. Phantom studies comparing known and SPECT measured concentrations showed a good correlation for 131I (r = 0.98, s.e.e. = 20.94 counts/voxel) for phantoms of 25 to 127 cc and concentrations of 0.13 to 9.5 microCi/cc. The in vivo, in vitro correlation of 131I concentrations in the urine was also good (r = 0.98, s.e.e. = 0.677 microCi/cc). Quantitative SPECT was used to calculate the effective half life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients. SPECT was also used to determine the dosimetry of [131I]MIBG (metaiodobenzylguanidine) in two patients with carcinoid, two with neuroblastoma, and one with pheochromocytoma. The radiation dose for thyroid carcinoma metastases varied between 6.3 and 276.9 rad/mCi. The dose from MIBG varied between 13.4 and 57.8 rad/mCi. These results indicate the validity of quantitative SPECT for in vivo measurement of 131I and the need to measure the concentration of 131I in individual human tumor sites. PMID- 2266392 TI - Diagnosing prosthetic joint infection. PMID- 2266393 TI - Management of patients with thyroid carcinoma: application of thallium-201 scintigraphy and magnetic resonance imaging. AB - Thyroid carcinoma has the ability to concentrate radioiodine, an attribute that can be used both for detection of thyroid cells and for treatment. Unfortunately, however, radioiodine uptake is not observed in all patients and a radioiodine scan requires that the patient be rendered hypothyroid for 4-6 wk. In the present study, we analyzed the utility of thallium-201 scanning and the usefulness of magnetic resonance imaging (MRI) in the detection of thyroid cancer. Nineteen patients with thyroid cancer had a total of 24 radioiodine scans, 33 thallium scans, and 10 MRI examinations. Of the 19 patients in the study, 17 had differentiated thyroid carcinoma. In these 17 cases, all paired studies were concordant for the presence (n = 7) or absence (n = 10) of disease. However, in one case (Patient 10), the 201Tl studies showed far more extensive disease than was observed on the 131I scan. Thyroid cancer was also detected on seven MRI studies. In summary, thallium and MRI scans are adjunctive techniques to radioiodine scanning that can either confirm the presence of neck bed activity, residual disease or metastatic cancer and may delineate tumor deposits not detected by radioiodine scanning. Thallium may be capable of detecting tumor deposits even while a patient remains euthyroid. PMID- 2266394 TI - Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer. AB - Indium-111-antimyosin (111In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01]. HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy. PMID- 2266395 TI - Antimyosin cardiac imaging: will it play a role in the detection of doxorubicin cardiotoxicity? PMID- 2266397 TI - Sombreros cientificos. PMID- 2266396 TI - Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non tumored tissue in patients with colorectal carcinoma. AB - Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation. PMID- 2266398 TI - Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion. AB - Generator produced positron-emitting radionuclides could potentially expand the application of positron emission tomography (PET) to centers that do not have access to a local cyclotron. The zinc-62/copper-62 radionuclide generator system could serve as a source of positron-emitting copper-62 (62Cu) (t1/2 = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/copper-62 generators capable of high output (greater than 300 mCi) and used the no-carrier added eluate in a rapid high yield synthesis of [62Cu] Cu(PTSM) that provides the radiopharmaceutical in a form suitable for intravenous injection (where Cu(PTSM) = pyruvaldehyde bis(N4-methylthiosemicarbazonato) copper(II]. We then demonstrated in pilot studies that [62Cu]Cu(PTSM) provides high quality brain and heart images with PET, accurately delineating cerebral and myocardial perfusion in both experimental animals and in humans (corroborating results of previous experimental studies utilizing longer-lived copper isotopes). The results of this work demonstrate that 62Cu can be conveniently obtained from high-level generators and, when used to label Cu(PTSM), provides a generator-produced radiopharmaceutical capable of providing estimates of cerebral and myocardial perfusion independent of cyclotron-produced radionuclides. PMID- 2266399 TI - 6-[18F]fluoro-L-fucose: a possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography. AB - The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6 [18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model. PMID- 2266400 TI - Correlations between uptake of technetium, calcium, phosphate, and mineralization in rat tibial bone repair. AB - Technetium-99m-(99mTc) phosphates are extensively used for detection of bone formation and resorption. The present is a study of 99mTc incorporation during bone remodeling. Uptake of 99mTc-labeled phosphate was studied in an animal model of primary osteogenesis following tibial marrow injury and incorporation was correlated to that of calcium-47 (47Ca), phosphorus-32 (32P), and with matrix vesicle calcification. Isotope uptake on Day 6 in the whole bone was increased compared to controls. On this day, an increase in vesicular diameter and distance from the calcified front was previously observed. Technetium-99m-labeled phosphates were detected only in the organic phase. Phosphorus-32 and 47Ca were detected in both organic and inorganic phases. It is suggested that 99mTc serves as a specific marker to the anabolic phase of remodeling. Increased incorporation of 99mTc during bone healing indicates enhanced organic matrix formation and not calcification. PMID- 2266402 TI - The indium white blood cell scan in the evaluation of osteomyelitis. PMID- 2266401 TI - Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats. AB - The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In IgG for imaging focal sites of infection in experimental animals. PMID- 2266403 TI - Phosphorus-32-colloidal chromic phosphate: treatment of choice for malignant pericardial effusion. AB - A 68-yr-old male with agnogenic myeloid metaplasia was given phosphorus-32 colloidal chromic phosphate intrapericardially for the treatment of malignant pericardial effusion. Technetium-99m-sulfur colloid was used to verify catheter placement and to visualize distribution within the pericardium. Estimated dosimetry for this mode of therapy is presented, and it is suggested that pericardial administration of phosphorus-32-colloidal chromic phosphate is the treatment of choice for malignant pericardial effusion. PMID- 2266404 TI - Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: case report. AB - A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female. Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-(99mTc) colloid, 99mTc-diethyliminodiacetic acid, and 99mTc-labeled red cells failed to demonstrate any abnormalities. These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion. The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia. PMID- 2266405 TI - In vivo cross-match by chromium-51 urinary excretion from labeled erythrocytes: a case of anti-Gerbich. AB - We studied a patient with an alloantibody to the high-frequency red blood cell (RBC) antigen Gerbich. A nationwide search for rare Gerbich-negative blood (less than 1:45,000 donors) located only seven units, and our supply was quickly exhausted. By using an in vivo cross-matching method, we demonstrated that this anti-Gerbich did not cause RBC destruction. Regular Gerbich-positive transfusions could then proceed without hemolysis. This cross-match test was based on the determination of the urinary excretion rates of injected radioactive chromium labeled donor erythrocytes by which it was possible to determine compatibility only 24 hr after the test was begun. The procedure provides an easy and accurate means for in vivo cross-matching of conventionally incompatible donor blood. PMID- 2266406 TI - In praise of the mighty red cell. PMID- 2266407 TI - Interactive three-dimensional region of interest analysis of HMPAO SPECT brain studies. AB - An interactive computer program has been developed to align a three-dimensional region of interest (ROI) model to technetium-99m-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) studies of the brain. The ROI model subdivides the human brain into fourteen discrete regions. A study was performed to determine normal ranges for HMPAO uptake in the ROIs defined by the model, and to assess the relative interobserver variability using the fitting program. HMPAO SPECT studies of twelve normal volunteers were independently analyzed by four observers. Small but significant differences between operators occurred primarily because of difficulty in defining the angle of the orbitomeatal plane on sagittal SPECT images. Despite this difficulty, the program and model have proven useful in defining ranges for normal cerebral perfusion in a healthy adult population. A study of a small group of patients with Alzheimer's dementia suggests that this procedure may be of use in the diagnosis of this disease. PMID- 2266408 TI - Program for PET image alignment: effects on calculated differences in cerebral metabolic rates for glucose. AB - A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states. PMID- 2266409 TI - Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples. AB - A detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples. This technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds: shorter acquisition times due to the high sensitivity, easier sample handling, direct quantification and the ability to perform dynamic studies. The detector performance shows a spatial resolution of 0.9 mm for carbon-14 (14C) (0.156 MeV), good linearity and homogeneity. The noise level is below 50/(cm2.sec). Successful imaging with this system has been performed with beta-emitters 14C, sulfur-35 (35S), iodine-131 (131I), yttrium-90 (90Y), and positron emitters gallium-68 (68Ga), and fluorine 18 (18F). Dynamic studies of axonal transport of 35S-methionine in a nerve, and static images of 90Y-labeled monoclonal antibodies in slices of tumors are presented. The system shows promise for rapid quantitative imaging of charged particle emitting radionuclides in small biologic samples. PMID- 2266410 TI - Three-dimensional functional images of myocardial oxygen consumption from positron tomography. AB - Images from positron emission tomography (PET) are usually presented as transaxial slices portraying tissue radioactivity. Studies can be difficult to interpret from transaxial images, and the temporal changes in tissue tracer concentrations which permit quantitative determinations of metabolism and perfusion are not displayed. We have developed a method to give quantitatively accurate three-dimensional images of myocardial oxygen consumption from serial images of the myocardial washout of carbon-11-acetate. Following i.v. bolus injection, data are collected for 20-30 min. The time-activity curves for each pixel in the transaxial slices are fit to a monoexponential function to determine the washout rate, which is directly related to the rate of myocardial oxygen utilization. Thus, functional images of myocardial oxygen consumption are produced for all seven slices of PET data. A previously developed method is then used to generate realistic and quantitatively accurate three-dimensional images. PMID- 2266411 TI - Spectral changes affect intrinsic count rate tests. PMID- 2266412 TI - Determination of brain death with technetium-99m-HMPAO. PMID- 2266413 TI - DOE-funded study releases data on radiation dose model for population near Hanford nuclear site. PMID- 2266414 TI - Lines from the president. Nuclear medicine's image--from the perspective of PET and turf. PMID- 2266415 TI - Old news is good news. PMID- 2266416 TI - Developing an inservice program on acquired immunodeficiency syndrome (AIDS). AB - Nurses often have negative beliefs about caring for people with the acquired immunodeficiency syndrome (AIDS) that may affect the care given their patients. The relation between these beliefs about caring for clients with AIDS and nurses' knowledge about such patient care is studied. A study of 515 registered nurses showed that the more knowledgeable RNs perceived they were, the more positive were their beliefs about caring for people with AIDS. Based on the results of this research, an AIDS inservice program is proposed that addresses the cognitive and affective learning needs of nurses. PMID- 2266417 TI - Pursuing ANA accreditation as a provider of continuing education in nursing. AB - Accreditation by the American Nurses' Association (ANA) recognizes the capacity of an organization to provide quality continuing education activities in nursing. The ANA accreditation system is described. Components of the process including the application, site visit, and final report are discussed. A cost/benefit analysis and suggestions for others considering ANA accreditation are included. PMID- 2266418 TI - Staff development opportunity and nurse job satisfaction, organizational commitment, and intent to remain in the organization. Implications for staff development. AB - In a time of financial constraints in health care, it is essential that nursing staff development in hospitals--a costly part of the budget--make a difference. The findings of the following study supported a positive relationship between nurse satisfaction with hospital-sponsored nursing staff development and the nurse's job satisfaction, commitment to the organization, and intent to remain employed in the organization. PMID- 2266419 TI - Nurses' perceptions of their health educator role. AB - A questionnaire was designed to describe and understand the role of the registered nurse in patient teaching as perceived by nurses. The questionnaire was distributed to 1355 nurses working in an acute care tertiary teaching hospital. The data indicated most nurses expressed strong agreement with the majority of items relating to their skill and educational preparation to teach patients. Selected questions relating to the nurse's role as a patient educator showed nurses viewed their patient education role as satisfying and expected by their patients. Needs relating to their patient education role included: additional time to teach patients, more educational materials, peer feedback regarding teaching effectiveness, and sufficient medical information. Additionally, the majority of nurses perceived that patients did not have sufficient knowledge to care for themselves after leaving the hospital and that too much information about their condition was withheld from them. Summary scales showed significant differences in area of work and position with the nurse's perception of the health educator role. PMID- 2266420 TI - Advancing staff nurse competencies. From novice to expert. AB - Staff nurses are responsible for providing care to acutely ill patients, therefore, educators and managers can no longer be comfortable with developing staff to a basic level of competence; they have the responsibility to develop expert practitioners. To achieve this goal, a program using the "novice-to expert" model for developing educational programs for each level of proficiency is described. PMID- 2266421 TI - A plan for staff development in gerontologic nursing. AB - Although aging of the population is evident and increased use of health services by the elderly is well-documented, the knowledge base of acute-care nurses in gerontologic nursing may be insufficient. Nursing staff development educators are in a strategic position to respond to this deficit. The approach used by an 800 bed Veterans Administration Hospital to determine the gerontologic learning needs of its nursing staff and a plan to meet these needs is reported. Recommendations for other organizations that plan to provide staff development in gerontologic nursing are offered. PMID- 2266422 TI - Professional development framework. Pathway to the future. AB - Staff development educators in a large midwestern university hospital developed a framework for professional development. The framework, applicable to all nurses, has four levels of professional development, from professional awareness to professional mastery. Within each developmental level five dimensions of nursing practice are identified: nursing process and practice skills, communication/collaboration, leadership, professional integration, and research/evaluation. This framework for professional development is reported and its potential use in the areas of planning, development and evaluation of staff development programs; restructure of a clinical ladder for nurses; and individual career development is discussed. PMID- 2266423 TI - An internship program's influence on recruitment and retention. PMID- 2266424 TI - The Nursing Fellowship: innovation in staff development. AB - The Nursing Fellowship is an example of a staff development program developed to meet the current day needs of nurses and hospitals. Across the country, hospitals are confronted with a paucity of specialty-prepared registered nurses. The Fellowships prepare RNs for certification examinations offered by the national specialty organizations. The Fellowships are under the umbrella of the Institute for Advanced Nursing Clinical Education and include: Oncology, Critical Care, Gerontology, Psychiatry, Medical Surgical, Perinatal and Perioperative Nursing. They are didactic and clinical and are developed and led by Master's-prepared clinical nurse specialists who are certified in the specialty area. The Fellowships continue to evolve but appear both subjectively and objectively to be successful in increasing knowledge in the specialty area. Early evaluation of the Fellowships suggests they may be an important tool for recruitment purposes and in retention of nursing staff. PMID- 2266425 TI - Lowering the cost of lowering the cholesterol: a formulary policy for lovastatin. AB - OBJECTIVES: To describe a medical center policy designed to contain the cost of using the lipid-lowering drug lovastatin in a primary care setting, to examine the effect of the policy on cost containment, and to examine physician acceptance of the policy. SETTING: A Veterans Affairs medical center. INTERVENTIONS: The policy made lovastatin available to physicians when failure of therapy with diet and two first-line drugs was documented on an order form. The form also contained educational information including prices and recommended niacin as the drug treatment of first choice for most patients. DESIGN: To evaluate the effect of the policy, lipid-lowering drug use at the medical center was compared with that at a similar center that did not restrict lovastatin use, and with lipid-lowering drug use in the United States as a whole. A written questionnaire was used to survey physician reaction to the policy. RESULTS: The use of lovastatin as a percentage of total lipid-lowering drug use at the center with the lovastatin policy was one-fourth that at the other center or nationwide, and the use of niacin was four times greater (p less than 0.0001). The estimated savings in drug costs to the center with the lovastatin policy due to these differences was more than $30,000 per year. In the survey of physicians affected by the policy (n = 78, response rate = 100%), less than one-fourth viewed it unfavorably, and 90% favored this policy over restricting the drug to a subspecialty clinic. CONCLUSION: The authors' experience indicates that a formulary policy that permits limited use of an expensive drug in a primary care setting can contain costs in a way that is acceptable to physicians. A policy of this type could be useful to the increasing number of health care provider organizations that cover the cost of outpatient medications. PMID- 2266426 TI - Estrogen and progestin therapy to prevent osteoporosis: attitudes and practices of general internists and gynecologists. AB - STUDY OBJECTIVE: To assess combined hormone therapy (CHT) prescribing patterns, possible impediments to CHT prescribing, and use of endometrial biopsy to monitor therapy. DESIGN: Mailed questionnaire survey. SUBJECTS: Gynecologists and general internists at two Boston teaching hospitals. MEASUREMENTS AND MAIN RESULTS: Based on a 71% response rate, 72% of internists and 100% of gynecologists reported ever having prescribed CHT. Almost 60% of internists, compared with 8% of gynecologists, reported that over half of their female patients were older than 50 years of age. By logistic regression analysis of the internists' data, female gender of physician (odds ratio 11.0), belief that CHT decreases myocardial infarction risk (odds ratio 3.4), and knowledge of CHT's benefits and risks (odds ratio 2.8) were associated with prescribing. Endometrial biopsy was performed by a majority of physicians only when unexpected vaginal bleeding occurred and in cases of unclear menopausal transition. Physicians who were concerned about litigation were seven times more likely to perform baseline endometrial biopsy. CONCLUSIONS: In the authors' sample, as well as nationally, internists are more likely to provide care for menopausal women. Among internists, gender and knowledge are strongly associated with CHT prescribing. These findings have important educational implications if internists are to routinely provide information and counseling to women about osteoporosis and CHT. PMID- 2266427 TI - Reducing unnecessary coronary care unit admissions: a comparison of three decision aids. AB - OBJECTIVE: To determine whether published decision rules for ischemic heart disease have practical value in reducing unnecessary admissions to coronary care units. DESIGN: Prospective cohort study. SETTING: A community hospital emergency room. PATIENTS: 235 consecutive patients presenting to an emergency room with a chief complaint of chest pain. MEASUREMENTS: Clinical information, including observations needed to use previously published decision aids, was collected on special forms at the time of the emergency room visit. Follow-up information was obtained from the medical records of patients who were admitted and by telephone interviews with patients who were discharged. The authors compared the residents' actual decisions with the predictions of the decision aids regarding their ability to predict complications (that is, to identify patients who needed admission or intensive care). MAIN RESULTS AND CONCLUSIONS: None of the decision aids could reduce unnecessary admissions without seriously increasing the rate of inappropriate discharges. However, within the clinically relevant subgroup of patients for whom the decision to admit or discharge was not obvious on clinical grounds (those without complications on presentation whom the residents chose not to discharge), the decision aids examined, used in combination to verify the need for admission, might have safely averted some unnecessary admissions. PMID- 2266428 TI - Patient characteristics associated with the use of mechanical restraints. AB - STUDY OBJECTIVE: To compare the characteristics of restrained patients with those of unrestrained patients by assessing a number of medical, behavioral, and cognitive variables including a disruptive-behavior inventory. DESIGN: Case control study. SETTING: A 719-bed university-affiliated teaching hospital. PATIENTS: The 80 cases were patients identified by the nursing staff as having had a restraint applied within the last 24 hours prior to entry in the study. The 80 unrestrained controls were selected from the rooms adjacent to the cases' in order to match for proximity to the nursing station and nurse staffing. MEASUREMENTS AND MAIN RESULTS: Demographic data, data on diagnoses and treatments, results of the Folstein Mini-Mental State (MMS) test and an eight item disruptive-behavior inventory, and outcome information were obtained for each patient using a standardized procedure. Three important patient characteristics were significantly associated with restraint use in a multiple logistic regression model: disruptive behaviors, nursing assessment of risk of falling, and cognitive impairment. Cases were older than controls, but age was not an independent characteristic associated with restraint use when controlling for cognitive impairment, risk of falling, and disruptive behaviors. CONCLUSIONS: Restraint use was more likely in patients with disruptive behaviors, at risk of falling, and with cognitive impairment. Attention to these factors and alternative strategies for dealing with them may reduce the use of physical restraints. PMID- 2266429 TI - Association of self-reported injury and alcohol consumption in medical outpatients. AB - OBJECTIVE: This study was designed to examine the association between minor injury and level of alcohol consumption among adult outpatients. DESIGN: Self administered survey of alcohol use and level of injury in prior month. SETTING: Adult outpatients attending a university-based general internal medicine private practice. PATIENTS/PARTICIPANTS: During a four-month period, 1,011 patients aged 18-65 years were asked to complete questionnaires while waiting to see a physician. The 791 who completed all forms appropriately are included in this study. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The total number of drinks and the total number of injuries reported during the preceding month were calculated. Nondrinkers reported an average of 0.51 (SD = 1.18) injuries in the prior month; and drinkers, 0.92 (SD = 1.70) injuries. Minor injuries were reported more frequently by heavier alcohol consumers only among younger patients (RR = 1.88). There was no association between reported injury and alcohol consumption among patients over 50 years of age (RR = 0.90). CONCLUSIONS: Minor injury is associated with heavier alcohol consumption in younger patients attending a general medical practice, but not among older patients. Further research is needed to establish a causal relationship between alcohol drinking and minor injury. PMID- 2266430 TI - The use of formal prior directives among patients with HIV-related diseases. AB - OBJECTIVE: To examine the knowledge of, counseling about, and use of prior directives among patients with HIV-related disease. DESIGN: Cross-sectional survey with personal interviews that was part of the evaluation of a multi-site AIDS Health Services Program. SETTING: Outpatient clinics and AIDS community based organizations. PATIENTS/PARTICIPANTS: To be eligible for the survey, subjects had to be at least 18 years of age and enrolled in the AIDS Health Services Program for at least one month. 1,031 clients were interviewed in nine communities. MEASUREMENTS AND MAIN RESULTS: Of those surveyed, 61% had thought a moderate or great amount about naming a proxy for health care decisions. The majority (68%) of the patients knew about prior directives, yet only 35% had been counseled and only 28% had a prior directive. Of those counseled, physicians had counseled only 11% (38/359). Gay/bisexual men were more likely to have been counseled and to have executed a prior directive than were others. Counseling was associated with having obtained a prior directive. Counseled subjects were 3.5 times more likely to have obtained a prior directive than were those not counseled. CONCLUSIONS: A gap exists between subjects' knowledge and implementation of prior directives. To help bridge this gap, the authors recommend that physicians not only attend to the technical aspects of patient care, but also determine patient values concerning life-sustaining therapy and counsel patients on prior directives. PMID- 2266431 TI - Supportive evidence for the validity of the epidemiologic necropsy for gallstones. AB - OBJECTIVE: The epidemiologic necropsy measures the occurrence of unsuspected disease through the examination of necropsy records of patients who died for other reasons. The estimates of unsuspected disease derived from the epidemiologic necropsy should approximate what actually occurs in the living population. DESIGN/SETTING: To test this hypothesis, all necropsy records of adult patients at the University of Kansas Medical Center from 1950 to 1984 were examined for the presence of gallstones. Patients with previous cholecystectomy or whose gallstones were diagnosed during life were excluded. The data were stratified by age and race and compared with those of a screening survey from Canada, a surgical series from New York, two screening surveys from Italy, and one from Denmark. The crude necropsy detection rates and the rates from the screening surveys were standardized to the 1970 federal census for Kansas City. RESULTS/CONCLUSIONS: The standardized occurrence rates were similar and suggest that the epidemiologic necropsy accurately assesses the occurrence of asymptomatic gallstones in the living population, thus strengthening its validity as a research tool. PMID- 2266432 TI - Post-call transfer of resident responsibility: its effect on patient care. AB - OBJECTIVE: To determine whether transferring the care of patients to another senior resident the day after admission to the hospital adversely affects the efficiency and quality of care. DESIGN: Retrospective analysis of a natural experiment. SETTING: The general medical service of the Minneapolis Veterans Affairs Medical Center, a major tertiary teaching hospital of the University of Minnesota internal medicine residency program. PATIENTS/PARTICIPANTS: Subjects were all the patients admitted to the medicine service from 5:00 PM to 6:00 AM over an eight-month period. INTERVENTION: After 5:00 PM, half of the patients were admitted to the hospital by a cross-covering senior resident (CC group of patients), and their care was transferred to a different senior resident the following day. The other patients were initially evaluated by the primary senior resident (PE group of patients). Assignment to the different services was a random, sequential process. MEASUREMENTS AND MAIN RESULTS: The CC group had significantly more laboratory tests performed during their hospital stay than did the PE group of patients (44 vs. 32, p = 0.01), even when adjusted for length of stay. Using multiple linear regression to adjust for other clinical parameters including length of stay, DRG weight, and number of consults, the authors found that being a CC subject was a significant predictor of the number of laboratory tests obtained (p = 0.01). Furthermore, the median length of stay in the CC group (n = 74) was longer than that in the PE group (n = 72) (eight days vs. six days); this was of borderline statistical significance, using a two-sample median test (p = 0.06). CONCLUSION: Patients transferred to a different resident the day after admission had more laboratory tests performed and longer inpatient stays. PMID- 2266433 TI - Preferences for autonomy when patients are physicians. AB - OBJECTIVE: To assess physicians' preferences for patient autonomy when they are patients themselves. DESIGN: Data from practicing physicians attending a continuing medical education course were obtained by questionnaire. After adjustment for sociodemographic differences, data from the physician population were compared with similar data previously obtained from a patient population. PARTICIPANTS: One hundred fifty-one physicians (94% of the study population) agreed to participate. Ninety percent were primary care physicians. Fifty-eight percent practiced in the eastern United States. MAIN RESULTS: The physicians, like the regular patients, preferred that the principal role in decision making for their own illnesses be handled by their providers, not by themselves. As illness severity increased, physicians indicated significantly less desire for making decisions (p less than 0.01). The magnitudes of the effects of increasing illness severity upon the decision-making preferences of physician and regular patients were comparable (p = 0.53). Physician-patients, however, were slightly more interested than regular patients in making decisions (p less than 0.001). CONCLUSIONS: although physician-patients are slightly more interested than regular patients in making decisions, for the most part their preferences for autonomy resemble those of regular patients. These results suggest that medical knowledge and sociocultural factors are only minor determinants of patient attitudes towards autonomy. Rather, patients' preferences to be relieved of decision-making responsibility are better understood as part of the phenomenology of illness. PMID- 2266434 TI - The role of the physician as a healer in the twenty-first century. PMID- 2266435 TI - The general physician: past and future. PMID- 2266436 TI - Applications of neurolinguistic programming to medicine. PMID- 2266437 TI - Evaluating decision aids: the next painful step. PMID- 2266438 TI - Potential problems in the use of necropsy data in epidemiologic research. PMID- 2266439 TI - Residency reform: opportunity knocks. PMID- 2266440 TI - Complications of cocaine use. PMID- 2266441 TI - Examining the ABIM's evaluation form. PMID- 2266442 TI - Posterior hip dislocation associated with acute traumatic injury of the thoracic aorta: a previously unrecognized injury complex. AB - Posterior hip dislocation associated with acute injury to the thoracic aorta is a previously unrecognized injury complex. This study reveals that 8% of patients with posterior hip dislocation have associated injury to the thoracic aorta because of abrupt deceleration injuries. This study defines the association of traumatic posterior hip dislocation and acute traumatic injury of the thoracic aorta, describes the mechanism of injury, and discusses the evaluation of a patient with a suspected acute traumatic aortic injury. PMID- 2266443 TI - Hip fractures: a future epidemic? AB - Recent studies from the United Kingdom and Sweden have demonstrated a dramatic rise in the number of people with hip fractures. It is our hypothesis that New Zealand is experiencing a similar rise in the number of hip fractures. The number of elderly people (over age 65 years) admitted to public hospitals in New Zealand over a 38-year period was reviewed. In people over age 75 years, we observed a disproportionate increase in the number of fractures compared with the increase in population. The highest risk group was women over age 85 years. Because of the differing age-specific fracture rates, the proportion of females over age 85 increased from 17% in 1950 to 40% by 1987. Through weighted regression analysis of fracture rate and population predictions, the projected number of fractures in the year 2001 and 2011 was predicted. By 2011 the number of people sustaining hip fractures will more than double. The proportion of the very elderly (85+) will increase from 40 to 65%. PMID- 2266444 TI - Stress fractures of the femoral neck following strenuous activity. AB - Stress fractures of the femoral neck following sustained strenuous physical activity are uncommon. In 194 military recruits in elite basic training who had sustained 257 stress fractures, most of them in long bone diaphyses, nine such fractures were located in the femoral neck. Seven of these fractures were transverse and undisplaced, and were treated successfully by bed rest and non weight bearing for 6-8 weeks. The other two fractures displaced into a varus position. One of them was treated successfully by manipulation and plaster of paris spica immobilization. Solid union of the fracture followed within 3 months. The second displaced fracture was treated by two successive procedures of internal fixation because it did not unite after the first intervention and slipped again into varus position. It is therefore suggested that unstable stress fractures of the femoral neck should be initially operated on and stabilized by rigid internal fixation, in order to avoid displacement and severe disability. PMID- 2266445 TI - Operative stabilization of subtrochanteric fractures of the femur. AB - The records and radiographs of 35 patients with 36 fractures of the subtrochanteric area of the femur stabilized by either angle blade plate (ABP) or dynamic hip screw (DHS) fixation were retrospectively reviewed to evaluate and compare the efficacy of these two implants in the management of these injuries. Twenty of the 36 fractures were managed by ABP stabilization and 16 fractures by DHS stabilization. In each case, a priority was placed on reconstitution of the medial cortex, either by anatomic reduction and stabilization or by the liberal use of cancellous bone grafting. The patients were evaluated for fracture pattern, integrity of the reconstructed medial cortex, time to union, and complications related to implant use. The two fracture classification systems used in this report (Waddell or Sensheimer), although helpful in preoperative planning, did not provide prognostic insight into fracture healing. All 31 fractures with an acceptable reconstitution of the medial cortex united primarily. Three of the five fractures without an acceptable medial buttress united primarily, one required reoperation for a delayed union with implant failure, and one patient had a fatal pulmonary embolism. This study demonstrates the acceptability of either implant in the management of subtrochanteric fractures provided strict adherence to reconstruction of the medial cortex is accomplished. PMID- 2266446 TI - Short-term results of the nonoperated isolated anterior cruciate ligament tear. AB - A review of reports on nonoperative treatment of acute, isolated anterior cruciate ligament (ACL) tears shows a large variability in results. This may be caused by variations in study designs. To our knowledge, no prospective study on isolated ACL tears diagnosed through arthroscopy has been published. We are reporting the short-term results of a prospective study of 29 nonoperatively treated acute ACL injuries. All patients had a history of trauma, with contact sports resulting in 20 of 29 injuries. The mean age was 25 years. The mean follow up was 33 months. Of the 29 patients, 11 required ligament reconstruction in the follow-up period because of considerable instabilities. Only two patients kept their activity level. All but two patients had a positive pivot shift. The reconstructed group was younger than the nonoperated group, had a higher preinjury level of activity both in sports and daily life, and in general had a desire to stay at the preinjury level. The nonreconstructed group had a lower preinjury activity level and was willing to reduce their postinjury level. When suggesting nonoperative treatment to a young patient with an isolated ACL tear, the surgeon should emphasize the importance of abandoning contact sports and obtaining good muscle strength. A young patient in a knee-demanding profession or insisting on continuing knee-demanding sports should have an early reconstruction carried out. PMID- 2266447 TI - Lengthening of below-the-knee amputation stumps using the Ilizarov technique. AB - Patients with short, traumatic, below-the-knee amputations (BKAs) frequently function as if they have knee disarticulations. The goal of this study was to evaluate the results in patients who had lengthening of their BKA stumps to improved prosthesis fit and increase ambulation. Three patients with traumatic BKAs, who were left with insufficient stumps for proper prosthesis wear, have had their stumps lengthened by Ilizarov's technique of distraction osteogenesis. The lengthening process produced a moderate degree of pain, and all patients had a temporary decrease in their range of motion. Two patients lost a substantial amount of gained length secondary to early full weight-bearing. Despite these difficulties, the procedure produced longer, more durable stumps in all patients with no final loss of knee range of motion. PMID- 2266448 TI - Anterior sternoclavicular dislocation: a long-term follow-up study. AB - The long-term follow-up results of 13 patients with traumatic anterior sternoclavicular dislocations are described. The patients had a mean age of 36.2 (SD 17.9) years. Nine patients had serious concomitant injuries. Radiological examination had limited diagnostic value. For 12 patients, nonoperative treatment consisted of analgesics and immobilization. The results of treatment of 10 patients were evaluated after a mean follow-up period of 62.9 (SD 53.4) months. The results of treatment were good in seven patients, fair in two patients, and poor in one patient. We concluded that radiological examination has a limited value in diagnosing anterior sternoclavicular dislocations and that nonoperative management is the treatment of choice. PMID- 2266449 TI - Nonunion of the proximal humerus. A review of 25 cases. AB - Records of 25 patients with nonunion of the proximal humerus were reviewed retrospectively. The initial fractures included 19 two-part surgical neck fractures and six three-part fractures. Fourteen fractures were treated nonoperatively and 11 surgically. Nine of 11 of the initial internal fixations were unsatisfactory. At the time of fracture 16 patients had one or more significant medical illnesses. Nonunion of the proximal humerus was associated with considerable morbidity. Patients complained of pain, stiffness, and disability in association with shoulder dysfunction. Four treatment groups were evaluated. Patients who declined treatment and patients treated with nonreamed intramedullary nails had limited shoulder motion and pain without union. Patients treated with proximal humeral hemiarthroplasty had relief of pain but limited motion despite rotator cuff reconstruction. The best results of treatment occurred after open reduction with internal fixation and bone grafting. A tension band construction that fixed the rotator cuff and proximal humerus to a plate/shaft composite was used successfully in seven patients. Although satisfactory reconstruction of nonunion of the proximal humerus can be obtained, the results of treatment in this series were only fair. Only 48% (12 of 25 patients) had good results. PMID- 2266451 TI - The relative contribution of individual osseous circulations to diaphyseal cortical blood supply. AB - The potential contributions of periosteal, nutrient (medullary), and epiphyseo metaphyseal circulations, respectively, to cortical blood supply have been investigated by isolating each using a diaphyseal segment model. The periosteal circulation was isolated by creating and nailing a 2-cm segment of the adult rabbit tibial diaphysis. The medullary circulation was isolated by external application of a silastic sheath to a diaphyseal segment. The epiphyseo metaphyseal circulation was isolated by combining both techniques. The residual potential routes of blood supply to each isolated segment were studied by arterial radiography and by histology in a postmortem study and in a survival study at various times up to 4 weeks after the isolation procedure. Both centrifugal and centripetal arterial supply were observed in the postmortem study. In the survival study, cortical arterial perfusion was observed up to 4 weeks following isolation of the periosteal circulation but only up to 2 weeks following isolation of the nutrient (medullary) circulation. At 4 weeks, the segment was not perfused when supplied only by the epiphyseo-metaphyseal system. It would appear, therefore, that the periosteal circulation provides a potential source of arterial supply to the diaphyseal cortex. Furthermore, an intact periosteal circulation seems to be necessary if an isolated segment of cortical bone is to continue to be adequately perfused with blood. PMID- 2266450 TI - Management of severe musculoskeletal injuries of the upper extremity. AB - Limb salvage was successful in 25 patients treated for severe grade III upper extremity injuries. In a retrospective review of 20 men and five women, follow-up time averaged 26 months. These high-energy injuries were characterized by massive soft-tissue injury, highly comminuted fractures, and significant neurovascular injury. Farm, industrial, and vehicular accidents accounted for 80% of the cases. Over 50% of the patients had concomitant systemic and/or other significant extremity injuries. Initial treatment consisted of irrigation and debridement and fracture stabilization using external and/or internal fixation. An average of four additional surgical procedures was required to provide soft-tissue coverage and maximum possible functional recovery. Forty-eight percent of the extremities underwent free vascularized or pedicular flaps for coverage or reconstruction. At final follow-up observation, 12% of the extremities rated excellent, 20% rated good, 52% fair, and 16% were poor. Experience gained in managing these severe upper extremity fractures supports the following observations. (a) Grade III open fractures of the upper extremities are frequently associated with significant neural, vascular, and musculotendon injuries. (b) External fixation plays an important role in the stabilization of grossly contaminated fractures. (c) Residual functional disability is common, and most patients do not return to their previous occupation. (d) Staged reconstruction directed toward maximum functional return may take several years. PMID- 2266452 TI - Mechanical analysis of the factors affecting dynamization of the Orthofix Dynamic Axial Fixator. AB - Loading trials were conducted to identify mechanical factors affecting dynamization of a commercially available external fixator (Orthofix) that is designed to undergo free telescopic motion when axially loaded. Angular variations between the proximal and distal screw clamps and the telescoping fixator body failed to produce fixator binding (failure to dynamize) in any of the loading trials. However, binding was produced by applying external torques in magnitudes that occasionally occur during routine ambulation. The specific torque necessary to induce binding (typically 3-4 Nm) was only a weak function of axial load magnitude, axial loading frequency, or simulated fracture stiffness. Among several geometrical variables of fixator application, only the pre-extension of the telescoping body and circumferential misalignment between proximal and distal pin clusters had an appreciable influence on the threshold binding torque. Axial fixator motions were also monitored in a small adjunct clinical series of 22 dynamized tibial fractures. The fixator dynamized appropriately in 15 cases (68%). Three patients (14%) showed evidence of fixator binding, and another four (18%) had less than predicted slider excursions. The role of several design factors implicated in torque-induced fixator binding is discussed in light of the benchtop and clinical observations. PMID- 2266453 TI - Posterior radial head dislocation without ulnar fracture. AB - Posterior radial head dislocation without an ulnar fracture in an adult is a rare injury. The pathology is often unrecognized initially. The patient's resultant elbow motion becomes severely compromised. Prompt diagnosis and reduction of the dislocation yield excellent results. A review of the biomechanical studies of the elbow ligaments enables us to propose a pathophysiological model of this injury, and a case report and review of the literature are presented. PMID- 2266454 TI - Tophaceous gout simulating infection about a stainless steel plate. AB - A 55-year-old man developed acute symptoms suggestive of a late, deep infection 8 years after uncomplicated open reduction and internal fixation of fractures to the left ulnar and radial shafts. At the time of surgical debridement, tophaceous material was found surrounding the radial plate. Acute tophaceous gout surrounding fracture fixation devices has not been previously reported and is difficult to distinguish from a deep infection. PMID- 2266455 TI - Dorsal dislocation of the distal radioulnar joint secondary to plastic deformation of the ulna. AB - An unusual case of an unstable dorsal, distal radioulnar dislocation secondary to plastic deformation of the ulna is presented. The etiology and pathomechanics of this rare injury are reviewed. PMID- 2266457 TI - Carcinoid tumours of the appendix are different. PMID- 2266456 TI - Compartment syndrome as a presentation of non-Hodgkin's lymphoma. AB - An 80-year-old woman sustained an injury to her left leg and presented having a compartment syndrome. Biopsy at the time of fasciotomy revealed lymphoma infiltrating the muscles of the left leg. We conclude that tumors may present as compartment syndrome and should be included with the differential diagnosis. PMID- 2266458 TI - Growth fraction in lung tumours determined by Ki67 immunostaining and comparison with AgNOR scores. AB - Estimation of the growth fraction with the use of monoclonal antibody Ki67, which recognizes a nuclear antigen in proliferating cells, was compared with the nucleolar organizer region staining in 95 lung tumours. There was nuclear staining in most tumours; 12 tumours were negative. Cytoplasmic staining was observed in another seven tumours. The small cell carcinoma group had the highest mean Ki67 index (23.75); squamous carcinomas had a mean value of 15.71, adenocarcinomas 10.99, and large cell anaplastic 20.76. Carcinoids had few stained cells. Nucleolar organizer regions were demonstrated by the argyrophilic method (AgNOR). No correlation was found between Ki67 indices and AgNOR scores. Kinetic data obtained by the AgNOR technique were less discriminating in view of the overlap between scores of various groups including carcinoids. We conclude that use of the monoclonal antibody Ki67 is a more reliable method of assessing proliferative activity in lung tumours. This antibody may be effective in identifying slowly proliferating tumours which are less sensitive to chemotherapeutic agents. PMID- 2266459 TI - In situ distribution of transforming growth factor alpha in normal human tissues and in malignant tumours of the ovary. AB - The distribution of transforming growth factor alpha (TGF-alpha) in human normal tissues from the uterus, Fallopian tube, ovary, small and large intestine, lung, spleen, kidney, and skin was studied by immunohistochemistry. TGF-alpha was found in epidermis, bronchial epithelium, intestinal mucosa, renal tubules, endo- as well as in exocervical and endometrial epithelium, and in the serous epithelium of the Fallopian tube. No TGF-alpha was detected in the stromal components of any of the tissues nor in any of the pre- and post-menopausal ovaries studied. Twenty nine ovarian tumours including 23 ovarian carcinomas, one malignant mixed Mullerian tumour, two ovarian metastases of gastrointestinal carcinomas, one dysgerminoma, one sarcoma, and one fibroma were studied for TGF-alpha by the same immunohistochemical method. In 25 cases, specific cytoplasmic staining for TGF alpha of epithelial tumour cells could be demonstrated. The pattern and intensity of the TGF-alpha immunostain varied among the TGF-alpha-positive tumours. No TGF alpha was found by immunohistochemistry in the remaining four cases nor in the stromal tumour components of any of the lesions studied. Northern blot analysis for TGF-alpha mRNA was performed on 12 of the tumours. While the immunohistochemistry and blotting results correlated well in ten cases, discordant results were obtained in two lesions. PMID- 2266460 TI - c-erbB-2 oncogene expression in ovarian cancer. AB - One hundred and four common epithelial malignancies of the ovary were stained for c-erbB-2 using an affinity-purified polyclonal antibody 21N. Twenty-three out of 104 (22.1 per cent) showed cytoplasmic staining alone. Nine out of 104 (8.7 per cent) showed both membrane and cytoplasmic staining. In a multivariate Cox analysis with other known risk factors the relative risk for cytoplasmic staining alone was 1.456 (chi 2 = 1.71, P greater than 0.1) and for membrane and cytoplasmic staining 0.316 (chi 2 = 7.95, P less than 0.005). These results do not support an adverse prognostic effect of c-erbB-2 in our patients. PMID- 2266461 TI - Helicobacter pylori infection of gastric mucin cell metaplasia: the duodenum revisited. AB - The histological material of 158 Billroth II gastrectomy specimens, used for a former study that established a relationship between duodenal ulcers and the presence of gastric metaplastic epithelium in the duodenal bulb, was reinvestigated for the presence of Helicobacter pylori. The results show that in all duodenal ulcer patients with gastric mucin cell metaplasia H. pylori colonized the metaplastic epithelium accompanied by an inflammatory response. The intestinal mucosa was always negative for H. pylori. H. pylori-positive patients also had the micro-organism in their gastric antrum. The results further support the hypothesis that infection of gastric mucosa in the bulb by H. pylori underlies duodenal ulcer disease. PMID- 2266463 TI - Biliary epithelial cells from the liver of patients with primary biliary cirrhosis: isolation, characterization, and short-term culture. AB - Since biliary epithelial cells of the middle-sized interlobular bile ducts are targets for lymphocyte-mediated damage in patients with primary biliary cirrhosis (PBC), we have developed a method for isolating and maintaining these cells in short-term tissue culture. Intrahepatic biliary epithelial cells were isolated from small segments of liver removed at the time of transplantation. Cells were separated from a collagenase digest by immunomagnetic separation using Dynabeads coupled to a monoclonal antibody (HEA 125) specific for a biliary epithelial cell surface antigen. The yield was approximately 3 x 10(5) cells/g of liver. The isolated cells were characterized morphologically and ultrastructurally using light and electron microscopy, and immunocytochemically using HEA 125 and anti cytokeratin, anti-vimentin and anti-asialoglycoprotein receptor antibodies. By these criteria cells were judged to be identical to biliary epithelial cells from normal liver. The cells could be maintained in short-term tissue culture for up to 4 weeks without loss of biliary epithelial cell markers. Availability of interlobular biliary epithelial cells will be of value in future investigations of the pathogenetic mechanisms of PBC. PMID- 2266462 TI - The glomerular changes in children with reflux nephropathy. AB - While heavy proteinuria and focal segmental glomerulosclerosis (FSGS) are well recognized features of progressive reflux nephropathy in adults, little is known of their early evolution. We have studied the glomerular changes in renal biopsy specimens obtained from 24 patients aged 5.2-18.8 years, in whom urinary protein excretion was measured as early morning urine protein creatinine ratios, using the Coomassie blue dye-binding method. Segmental sclerotic lesions were found in eight biopsies and traced through serial sections to a hilar origin in every instance. There was a strong positive correlation between the extent of glomerular involvement and the amount of proteinuria (P less than 0.0001). Parahilar hyaline deposits were observed in 16 biopsies, including five of the eight showing FSGS. All unsclerosed glomeruli were enlarged, and the hilar arterioles showed both enlargement and thickening, their walls frequently containing subendothelial hyaline deposits. Since in most patients renal function was comparatively well preserved, despite extensive loss of renal substances, we believe that these glomerular and vascular changes represent the stages in the evolution of hyperfiltration. Microproteinuria is the earliest clinical manifestation of FSGS, and should be sought routinely in all patients with reflux nephropathy. PMID- 2266464 TI - The osteoclast, which derives from a haemopoietic stem cell, is not depleted in aplastic anaemia. AB - The osteoclast derives from the haemopoietic stem cell but its relationship with the other progeny of the haemopoietic system is unknown. Osteoclast numbers were assessed in patients with aplastic anaemia and were found not to be depleted compared with a control population. This suggests that the osteoclast may develop along a separate lineage which is independent of the colony forming unit granulocyte, erythroid cell, monocyte, and megakaryocyte (CFU GEMM). PMID- 2266465 TI - Silicone plastinated pathology specimens and their teaching potential. AB - Plastination is a process of tissue preservation by impregnation with silicone polymers or epoxy resins. The resulting specimens are dry, odourless, durable, life-like, non-hazardous, maintenance-free, and do not deteriorate with time. The technique may be easily mastered by those with a basic knowledge of histology laboratory practice. A small-scale system is relatively inexpensive to establish and specimens are comparable in cost to traditional 'pots'. Plastinated specimens are a useful adjunct to the teaching of pathology, anatomy, radiology, and surgery, and are particularly suited to use in small groups. They are much preferred to conventional 'pots' by both students and teachers owing to their accessibility, superior illustrative powers, and comparative ease of interpretation. PMID- 2266466 TI - QBEnd/10: a useful, but by no means specific, marker of Kaposi's sarcoma. PMID- 2266467 TI - 'EGF receptor' antibody 29.1.1. PMID- 2266468 TI - Preclinical evaluation of submillimeter diameter microwave interstitial hyperthermia applicators. AB - Ultra miniature coaxial cable has been used, with microscopic techniques, to fabricate interstitial hyperthermia applicators having diameters of 0.20 mm, 0.33 mm, and 0.58 mm; commercial applicators have a diameter of 1.1 mm. Animal studies with the 0.33 mm diameter applicators have shown that they produce less local tissue trauma than the larger-diameter devices. All of these applicators operate at 915 MHz and have similar heating patterns because they use the conventional monopole design and the catheters have been approximately scaled to the dimensions of each size applicator. We have measured the heating (SAR) patterns of these applicators in tissue-simulating phantoms, both singly and in arrays, using a miniature electric field probe. As an intermediate step to patient trials, we have examined the ability of these applicators to provide effective heating of perfused tissue, using pig thigh and liver as models. Test results suggest that the durability and power handling capabilities of our submillimeter applicators are adequate for use in patients. These new applicators should be useful in the percutaneous treatment of deep-seated tumors and in intraoperative treatments. The applicators also permit intraluminal or intravascular access to tumors. PMID- 2266469 TI - Preparation of controlled release anticancer agents. I: 5-Fluorouracil-ethyl cellulose microspheres. AB - Microspheres of 5-fluorouracil have been prepared, using three grades of ethyl cellulose as wall forming materials, and utilizing a solvent evaporation technique under ambient conditions. An alcoholic solution of 5-fluorouracil and polymer was dispersed in liquid paraffin containing 33.3 per cent n-heptane. The effect of stirring rate, time of stirring, drug loading, and polymer grade on drug release in two different media were evaluated. The drug loaded particles were spherical in shape and had a diameter range of 25-200 mm and were suitable for incorporating into a gel base. Drug release studies in aqueous media, showed that acidic media provide a faster release rate than neutral media. The drug release study from an aqueous gel base preparation at pH 7.0 through a synthetic membrane was found to be promising for formulation of a gel-microsphere product for the treatment of skin lesions. PMID- 2266470 TI - Effervescent granule based proliposomes of ibuprofen. AB - Proliposomes of ibuprofen were successfully prepared using effervescent granules as solid carriers of dried phospholipids along with other lipids (soyabean lecithin, stearylamine and cholesterol). Liposomes of regular size with uniform size distribution resulted when proliposomal formulations were hydrated under the effervescence produced by the production of carbon dioxide gas. The inert atmosphere of carbon dioxide gas prevents the chance of oxidative degradation of phospholipids. The size distribution of liposomes was noted to be related to the degree of agitation provided by effervescence. Encapsulation efficiency of liposomes derived from proliposomes was shown to be nearly 100 per cent. Preparations were shown to be quite stable at 20 degrees C when stored under an umbrella of nitrogen. The enhanced anti-inflammatory activity of ibuprofen entrapped in liposomes was exhibited when compared with plain ibuprofen following intravenous administration using the carrageenan induced paw oedema test. PMID- 2266471 TI - Egg albumin microspheres containing paracetamol for oral administration. I. In vitro characterization. AB - Different egg albumin microsphere systems for oral administration of paracetamol were prepared by the emulsion and capillary extrusion methods. The size of the microspheres depended on the method used to produce the microcapsules and also the size of the crystals of paracetamol. The effect of the following factors on in vitro dissolution were studied: different denaturation processes, variation in the ratio of paracetamol to albumin, size of microspheres, remnant oil in the microspheres, and the coating of the microspheres with membranes of polymethacrylates (Eudragit). The most important factors to control the release of paracetamol from the microspheres were the denaturation process and the use of waxes and membranes to delay the release of paracetamol from the microspheres. The egg albumin microspheres were very porous and permeable to water and thus the release of the paracetamol from the matrix was usually fast unless the microspheres were suitably coated, with, for example, Eudragit RL or RS. PMID- 2266472 TI - Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation. AB - Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed. PMID- 2266473 TI - Dermal drug delivery by liposome encapsulation: clinical and electron microscopic studies. AB - The fate of liposomes and the encapsulated drug was studied after topical application on the skin. Lidocaine applied on the forearm of human volunteers produced greater local anaesthetic effect in the liposomal form than in the cream form (p less than or equal to 0.001 after 1 h application). Autoradiography demonstrated higher concentration (p less than or equal to 0.01) of 14C-lidocaine in the epidermis and dermis of guinea pigs treated with liposome-encapsulated lidocaine as opposed to lidocaine in Dermabase cream. Electron microscopic observations, using colloidal iron as an electrodense marker, indicated that intact liposomes penetrated into the skin and deposited in the dermis where they acted as a slow release depot system. On the basis of results in the human volunteers and animals, a hypothetical model for liposome-skin interaction is proposed. PMID- 2266474 TI - Separation of drug-loaded nanoparticles from free drug by gel filtration. AB - A suitable method for separating free drug and other residual compounds from drug loaded, colloidal polymeric particles was developed. The objective of this separation procedure was to purify particle suspensions on a preparative scale by a rapid, simple, and exact method without changing the properties of the particles. The gel filtration method described in this paper using a middle pressure chromatographic system is able to meet all these requirements. The separation process could be optimized by using only water as an eluent in combination with Sephadex G 50 medium. The purified particles appeared after 12 13 min in the eluate. Neither dispersity nor particle size or loading rate were influenced to a considerable extent. PMID- 2266475 TI - High encapsulation efficiencies in sized liposomes produced by extrusion of dehydration-rehydration vesicles. AB - In an attempt to produce sized liposomes with high encapsulation efficiency by a gentle procedure, we compared the encapsulation efficiency in liposomes of three different molecules: carboxyfluorescein (mol.wt 376 Da), protein A (mol. wt 40,000 Da), and a DNA-plasmid pN2 alpha 1AT (9.3 kb). Sized liposomes were obtained by extrusion of multilamellar vesicles through polycarbonate filters of defined pore size (0.2 micron). Multilamellar vesicles were formed by mechanical dispersion of dried egg phosphatidylcholine (PC) and cholesterol (CH) at molar ratio 1:1 in an aqueous buffer (MLVs) or by dehydration-rehydration procedure (DRVs) where small unilamellar vesicles (SUVs) obtained by probe sonication of PC:CH (1:1) in water were dried in the presence of the desired agent by lyophilization and then rehydrated in one tenth of the original volume. Our results show that, in all cases, the higher encapsulation efficiencies were obtained by dehydration-rehydration vesicles (DRVs) and that the ratio material/lipid in sized DRVs (S-DRVs) increased three- to four-fold with respect to sized liposomes (S-MLV) obtained by extrusion of MLVs. In addition, plasmid electrophoresis on agarose gels (0.8 per cent) showed that no detectable DNA fracture was produced in the encapsulation process. In summary, we showed that extrusion through polycarbonate filters of preformed DRVs is a gentle procedure which enhances the encapsulation efficiencies in sized liposomes of molecules with clearly different molecular weight and structure. PMID- 2266476 TI - Influence of partition parameter on release of drug from adjuvant-containing charged film microcapsules. PMID- 2266477 TI - Effect of surfactants on the stability of modified egg-yolk phosphatidyl choline liposomes. AB - Disintegration by surfactants on egg-yolk phosphatidyl choline (PC) vesicles, stabilized with polycholesteryl methacrylate and carboxy methyl chitosan, was investigated by measuring the amount of marker dye (bromothymol blue) released from the vesicles. In all the studies at pH 7.4 anionic and nonionic surfactants caused vesicle disintegration at low concentrations while cationic surfactants produced breakdown of vesicles at high concentrations. It was found that the modified liposomes disintegrated in the following order: Polymeric liposomes less than carboxymethyl chitosan coated/stearic acid/oleic acid containing PC liposomes less than cholesteryl methacrylate monomer containing PC liposomes/PC liposomes Polymeric liposomes were found to be the most stable compared with all other types. This may be explained due to the filling of the pores in the lipid structure which in turn block the surfactant penetration into phospholipid bilayers. In contrast to unsaturated fatty acid (oleic acid) saturated fatty acid (stearic acid) containing liposomes are more stable. PMID- 2266479 TI - Ibuprofen-loaded ethylcellulose microspheres: release studies and analysis of the matrix structure through the Higuchi model. AB - The following work deals with ibuprofen-loaded ethylcellulose microspheres. The drug exists either in a state of molecular dispersion or in crystalline form, depending on the encapsulation ratio. The in vitro release profiles have been studied and the Higuchi model applied to the experimental results. With an appropriate treatment of the results, it has been shown that the surface crystals responsible for the observed burst effect are really encapsulated by the polymer. The calculation of the tortuosity factor clearly shows that the release kinetics are controlled by the hydrophobicity of ethylcellulose and the geometry of the porous volume resulting from the dissolution of ibuprofen crystals. It thus appears that crystals are probably differently distributed in the matrix depending on the microsphere size. PMID- 2266478 TI - Study of shellac-glycerol esters as microencapsulating materials. II. Quantitative correlation between physicochemical properties and release characteristics. PMID- 2266480 TI - Relative contributions of expressive behavior and contextual information to the judgment of the emotional state of another. AB - This study used a technique for assessing the relative impact of facial-gestural expressions, as opposed to contextual information regarding the elicitor and situation, on the judgment of emotion. In Study 1, 28 undergraduates rated videotapes of spontaneous facial-gestural expressions and separately rated the emotionally loaded color slides that elicited those expressions. The source clarities of the expressions and slides were matched using correlation and distance measures, and 18 expressions and 9 slides were selected. In Study 2, 72 undergraduate receivers were shown systematic pairings of these expressions and slides and rated the emotional state of the expresser, who was supposedly watching that slide under public or private situational conditions. Expressions were found to be more important sources for all emotion judgments. For female receivers slides were relatively more important in the public than in the private situation. PMID- 2266481 TI - Coping and adaptation to facial pain in contrast to other stressful life events. AB - This article investigates whether coping with chronic pain influences adaptation to other negative life events using data on Temporomandibular Pain and Dysfunction Syndrome (TMPDS) patients (N = 99) and nonpatient controls (N = 98). It is found that cases cope very differently with pain than with other stressful events and that cases and controls do not differ on coping with nonpain events, with 2 exceptions. Cases view nonfateful events as more outside their control and they have more negative changes in usual activities following negative events. This excess of negative change is associated with greater demoralization and physical exhaustion. It is concluded that coping with repeated pain episodes leaves cases vulnerable to stressful events. Alternative interpretations, especially those involving the role of preexisting personality differences, are discussed. PMID- 2266482 TI - Adolescents' reference-group choices, self-esteem, and adjustment. AB - Three hundred thirty Black, Hispanic, Asian, and White high school students reported their reference-group label as mainstream, bicultural, or strongly ethnically identified. Compared with other groups, White students were significantly more likely to be mainstream. Across ethnic groups, students reporting a strong ethnic identification held attitudes that were significantly more separatist, reported more ethnic pride, engaged in less cross-ethnic contact out of school, reported more cross-ethnic conflict, and used English significantly less often than other reference groups. Reference-group label was not associated with significant ethnic differences in self-esteem, social competence, or grade point average. The generational status of minority students is discussed as a potential influence mediating the impact of reference group on adjustment. PMID- 2266483 TI - Attribution difficulty and memory for attribution-relevant information. AB - This research compared the processing and retrieval of attribution-relevant information when the attributional inference is easy or difficult to make. Subjects attributed behavioral events to the person or to the situation, based on several items of context information. Each context sentence implied either the person or the entity as causal agent. When the attributional inference was difficult to make (an equal number of context sentences implied actor and entity as the causal agent), subjects recalled more of the behavioral events, recalled more context sentences, and were less confident in their attributions than when the attributional inference was easy to make (most context sentences implied the same causal agent). Subjects also recalled context information that was implicationally incongruent with the majority of the other context sentences with a higher probability than when that same information was implicationally congruent. PMID- 2266484 TI - Reconsidering the attribution-adjustment relation following a major negative event: coping with the loss of a child. AB - Field studies have not yet conclusively established how attributions affect adjustment to unanticipated traumatic events. This may be due, in part, to the adoption of several untested assumptions in most prior research. It has usually been assumed that attributional issues are important to people who experience a traumatic event, that such concern is adaptive, and that specific attributions (e.g., self-blame) influence subsequent adjustment. These assumptions were tested with longitudinal data collected over 18 months from 124 parents whose child died of Sudden Infant Death Syndrome. By 3 weeks postloss, 45% of parents were not concerned with attributional issues. These parents were less distressed and less likely to blame themselves or others for the death. Longitudinal analyses did not support the assumption that attributions influence subsequent adjustment. Rather, attributions to onself or others appear to be symptomatic of distress. PMID- 2266485 TI - Victim and perpetrator accounts of interpersonal conflict: autobiographical narratives about anger. AB - Subjects furnished autobiographical accounts of being angered (victim narratives) and of angering someone else (perpetrator narratives). The provoking behavior was generally portrayed by the perpetrator as meaningful and comprehensible, whereas the victim tended to depict it as arbitrary, gratuitous, or incomprehensible. Victim accounts portrayed the incident in a long-term context that carried lasting implications, especially of continuing harm, loss, and grievance. Perpetrator accounts tended to cast the incident as a closed, isolated incident that did not have lasting implications. Several findings fit a hypothesis that interpersonal conflicts may arise when a victim initially stifles anger and then finally responds to an accumulated series of provocations, whereas the perpetrator perceives only the single incident and regards the angry response as an unjustified overreaction. Victim and perpetrator roles are associated with different subjective interpretations. PMID- 2266486 TI - Bacterial polymers: physicochemical aspects of their interactions at interfaces. AB - How do bacteria stick to a surface? There is still not enough information about to answer this question especially at the molecular level. This question only gives rise to more questions. What is the structure of the true adhesive bacterial polymer? Is only one bacterial polymer or several polymers involved in the adhesion process? What is the role of proteins associated with the bacterial polysaccharides? What type of polymer is produced for the adhesion to hydrophobic surfaces? Is the polymer produced as a response to the surface? This review is an attempt to summarize the physicochemical aspects of bacterial polymers and their interaction with surfaces. It was tried to give an overview of the literature published in this field. The article is divided into the following sections: first, the forces involved in bacterial adhesion are discussed. Third, different fluid conditions are investigated. Fourth, the nature of different bacterial polymers which are important for the interaction with a surface is elaborated. Fifth, the current knowledge about biological polymers at interfaces is shown. And sixth, the role of polymers in the adhesion of bacteria available to date is highlighted. PMID- 2266487 TI - Role of host and bacterial factors in modulating staphylococcal adhesion to implanted polymer surfaces. PMID- 2266488 TI - Surface proteins of coagulase-negative staphylococci: their role in adherence to biomaterials and in opsonization. AB - During the last decade coagulase-negative staphylococci (CN-Staph) have clearly emerged as pathogens in patients equipped with foreign devices. This has fueled the interest in these bacteria considerably and as a result, knowledge of the biology of CN-Staph as well as insight into the pathogenesis of biomaterial associated infections due to these bacteria are rapidly expanding. Adherence of bacteria to biomaterials is a necessary step in the process of these infections. Evidence is accumulating that surface proteins of CN-Staph are essential in the early phases of adherence to biomaterials. By using monoclonal antibodies in immunoblotting and immune electron micrography we have identified a cell wall protein complex apparently located on the surface of CN-Staph and involved in adherence to biomaterials. Further studies will be oriented at characterization of the protein adhesin(s) and at identification of the surface structures with which the adhesion is associated. PMID- 2266489 TI - Physical chemical description of bacterial adhesion. AB - For the description of general bacterial adhesion phenomena two different physicochemical approaches are available. The first one, based on a surface Gibbs energy balance, assumes intimate contact between the interacting surfaces. According to this approach adhesion is solely related to the Gibbs energies of the surfaces involved. The second approach, based on colloid chemical theories (DLVO theory), allows for two types of adhesion: 1. secondary minimum adhesion, which is often weak and reversible, and 2. irreversible primary minimum adhesion. In the first case a thin water film is present between the interacting surfaces. In the DLVO approach adhesion is determined by long range interactions, i.e., Van der Waals and electrostatic interactions. Van der Waals interactions may be related to the hydrophobicity of the cell wall. For the measurement of bacterial hydrophobicity and electrokinetic potential several macroscopic methods are available. Based on a literature review of the influence of both surface characteristics on adhesion, it is concluded that the surface Gibbs energy balance approach is not adequate to describe the majority of adhesion phenomena. On the other hand the DLVO-theory describes the observations fairly well, especially in the case of reversible (secondary minimum) adhesion. The influence of adsorbing (in)organic compounds, extracellular polymers and cell surface appendages on adhesion can also be predicted by a DLVO-type approach. PMID- 2266490 TI - Fungal flora associated with combine harvester wheat and sorghum dusts from Egypt. AB - 107 species and 8 species varieties belonging to 44 genera were collected from combine harvester wheat and sorghum dusts (35 genera and 91 species + 4 varieties) and from the atmosphere of their hay sites (26 genera and 69 species + 4 varieties) on glucose- and cellulose-Czapek's Dox agar at 28 degrees C and 45 degrees C. The mycoflora of wheat and sorghum dusts were basically similar on the two types of media and the most common fungi were: Alternaria alternata, Aspergillus flavus, A. fumigatus, A. niger, A. ochraceus, A. sydowii, A. terreus, Cochliobolus spicifer, Emericella nidulans, Fusarium moniliforme, Penicillium chrysogenum, P. duclauxii, P. funiculosum and P. oxalicum. Truly thermophilic species were frequently encountered from the two substrates: Chaetomium thermophilum, Humicola grisea var. thermoidae, H. insolens, Malbranchea pulchella var., sulphurea, Rhizomucor pusillus, Sporotrichum thermophilum, Talaromyces thermophilus, Thermoascus thermophilus and Thermomyces lanuginosus. The airborne fungi in the two atmospheres were basically similar and the most prevalent species were members of Alternaria (1 species), Aspergillus (18 species + 2 varieties), Chaetomium (2 species), Cochliobolus(3 species), Emericella (3 species + 2 varieties), Fusarium (3 species), Mucor (1 species), Penicillium (14 species) and Stachybotrys (1 species). PMID- 2266491 TI - L-carnitine uptake by Escherichia coli. AB - The uptake of L-carnitine by Escherichia coli 044 K74 which is able to metabolize L-carnitine to gamma-butyrobetaine under anaerobic conditions was studied. The uptake system of E. coli was induced in the presence of L-carnitine or crotonobetaine. The optimum influx of L-carnitine was found to take place at 37 degrees C in phosphate buffer, pH 7.5. On the basis of the temperature dependence of the uptake rate an activation energy of 53.5 kJ/mol was estimated. The transport of L-carnitine was energy dependent. The kinetics of L-carnitine entry followed the Michaelis-Menten relationship yielding a Km value of 5.3 x 10(-4) M and a Vmax of 154 nmol/min.mg protein. The transport system showed considerable structural specificity for trimethylamine carboxylic molecules. The results suggest that E. coli possesses an inducible, active and carrier-mediated uptake system for L-carnitine. PMID- 2266492 TI - Formation of a potent respiratory inhibitor at nitrite reduction by nitrite reductase isolated from the bacterium Paracoccus denitrificans. AB - A new method of dissimilatory nitrite reductase (cytochrome cd1) isolation from the periplasmic fraction of anaerobically grown cells of the bacterium Paracoccus denitrificans was developed, using ionex and gel permeation chromatography with FPLC system (Pharmacia, Sweden). In experiments with isolated enzyme it was shown that through a nitrite reduction, catalysed by this enzyme, a substance (presumably nitric oxide) was formed which at submicromolar concentrations inhibited terminal cytochrome oxidase of the respiratory chain of the same bacterium. These results help to explain formerly observed sensitivity of bacterial oxidase activity to NO2- and the mechanism of switching the electron flow from O2 to nitrogen terminal acceptors. PMID- 2266493 TI - Detection of a 2 mu derivative yeast plasmid with altered properties. AB - The Saccharomyces cerevisiae (Sacch. cerevisiae) strain RXII, like many others, harbours plasmid DNAs. and one category of them is homologous to the 2 mu plasmid of yeast. DNA-DNA hybridization experiments indicated altered structures of this species as regards the number and distribution of the restriction sites. The efforts made to clone either the whole plasmid in pBR328 or its fragments in pBR322 vectors remained unsuccessful, since deleted plasmids were isolated without insert DNA, and even the loss of vector sequences was observed. The data suggest, that the 2 mu derivative plasmid in strain RXII represent an unique category of this extrachromosomal genetic element. PMID- 2266494 TI - Protein extracts for nutritional purposes from fragile strains of Saccharomyces cerevisiae: construction of strains and conditions for lysis. AB - A superfragile strain, Saccharomyces cerevisiae 211, carrying three nonallelic nuclear determinants of cell lysis by osmotic shock was isolated from the haploid progeny of a cross between two laboratory fragile strains VY 1160 and SY 15. The strain Sacch. cerevisiae 211 is prototrophic, grows well in both laboratory and industrial media, only when supplemented with osmotic stabilizers. The average protein content of its biomass after growth in a molasses-based nutritional medium is 48.7%. In laboratory conditions this strain releases about 60% of its cellular proteins by spontaneous lysis in water. However, on a pilot scale the protein yield decreases to about 25%. After a single disintegration step at 650 atm, practically all of the cellular protein--91.5%, is extracted without any additional chemical treatment. This result cannot be reached in any of the wild type strains tested even after triple treatment at 650 atm. PMID- 2266495 TI - Pharmacokinetics and chronic toxicity of cyclosporine A in genetic hydroxylation deficient dark Agouti rats. AB - Since oxidation plays a key role in the metabolism of cyclosporine A (CsA), the pharmacokinetics and the toxicity of CsA was investigated in female dark Agouti rats exhibiting a deficiency for debrisoquine hydroxylation and for dextromethorphan demethylation. When compared with Wistar rats (n = 10), dark Agouti rats (n = 10) had a higher mean clearance (4.8 ml/min per kg vs. 3.3 ml/min per kg) and a lower mean residence time (606 min vs. 1361 min) after intravenous dosing of CsA. The systemic availability of subcutaneous CsA was close to 100%. The steady state CsA concentrations assessed by HPLC in whole blood after subcutaneous dosing of 20 mg/kg per day for 23 days (n = 10) were about 1000 ng/ml in dark Agouti rats. When compared with dark Agouti rats treated with cremophore (n = 10) or not treated at all (n = 12), dark Agouti rats on chronic subcutaneous CsA plus cremophore for 23 days (n = 10) had no difference in kidney histology but had slightly increased liver fatty changes. Rats on CsA and/or cremophore had a decreased uric acid clearance and evidence of hypoaldosteronism. The urinary ratio of debrisoquine/4-hydroxydebrisoquine decreased in rats on CsA, whereas the O-demethylation and N-demethylation of liver obtained from rats on cremophore was impaired. Thus, dark Agouti rats show no difference in the metabolism of CsA and when given CsA for 23 days show drug induced functional but no relevant structural light microscopic changes in the kidney, and functional and slight structural changes in the liver. PMID- 2266496 TI - Nonlinear pharmacokinetics and interconversion of prednisolone and prednisone in rats. AB - The pharmacokinetics of prednisolone and prednisone were examined in 32 rats at four intravenous doses (5, 10, 25, and 50 mg/kg). Each rat was given one dose of either intravenous prednisolone or prednisone, and plasma concentrations of both compounds were measured by HPLC. Mammillary moment analysis showed the apparent clearance and volume of distribution of prednisolone and the apparent clearance of prednisone to be dose-dependent. Further diagnostic analysis using a linear interconversion model revealed modest interconversion between the two steroids and at least two saturable clearance processes: the conversion of prednisolone to prednisone and the irreversible elimination of prednisone. A comprehensive model which incorporates the nonlinear clearances of prednisolone and prednisone plus the additional feature of nonlinear tissue distribution of prednisolone was then constructed. Four differential equations describing the rate of change of each steroid in each compartment were used to numerically fit by nonlinear least squares analysis all plasma concentration-time profiles simultaneously. The final estimates from the full model only partly agreed with the results from the two moment analyses but confirmed the general structure of the model. The nonlinear tissue distribution of prednisolone was reinforced by assay of muscle tissue. This study demonstrates the utility of the model-building process where simpler models yield insights into more elaborate schemes with complex nonlinear features. PMID- 2266497 TI - Physiological modeling of drug and metabolite: disposition of oxazepam and oxazepam glucuronides in the recirculating perfused mouse liver preparation. AB - The disposition of tracer doses of 3H-oxazepam was studied in the recirculating perfused mouse liver preparation. 3H-Oxazepam was biotransformed primarily to the diastereomeric 3H-oxazepam glucuronides, which either effluxed into the circulation or underwent biliary excretion. Three additional, unknown metabolites constituted a small fraction (5-10%) of the total radioactivity recovered in bile (7% of dose); no other metabolite was detected in perfusate. A physiologically based model, comprising the reservoir, liver blood and tissue, and bile, was fitted to reservoir concentrations of 3H-oxazepam and 3H-oxazepam glucuronides, and the cumulative amount excreted into bile. The model allowed for consideration of elimination pathways other than glucuronidation and the presence of a transport barrier for the oxazepam glucuronides across the hepatocyte membrane. The fitted results suggest a slight barrier existing for the transport of metabolites across the sinusoidal membrane, inasmuch as the transmembrane clearance was comparable to liver blood flow rate. Upon further comparison of estimates of formation, biliary, and transmembrane clearances for the oxazepam glucuronides, the rate-limiting step in the overall (biliary) clearance appears to be a poor capacity for biliary excretion. The influence of the cumulative volume loss that a recirculating perfused organ system incurs upon repeated sampling was discussed, and a compartmental method of correcting the observed concentrations of drug and generated metabolite was presented. PMID- 2266498 TI - Statistical moments and disposition parameters in a local perfusion system under mammillary nonequilibrium condition. AB - Application of the statistical moment analysis to the local organ perfusion system leads moment parameters (moments) from the venous outflow concentration time curve (dilution curve) of drug after its intra-arterial bolus injection. By introducing the chromatographic concept and the network theory, we had defined the disposition parameters such as steady state distribution volume, mean elimination time, and intrinsic clearance from moments based on the well-stirred model. In this paper, discussion was expanded to general two-compartment organ perfusion models and the meanings of these disposition parameters in them were investigated. The relationship between compartmentally defined microconstants and moments-oriented disposition parameters was examined and the effect of the nonequilibrium (mainly peripheral elimination) condition on the latter was discussed. The possible utility of the disposition parameters as noncompartmental indications of drug disposition characteristics was suggested. PMID- 2266500 TI - Attitude is everything. PMID- 2266499 TI - Comments on two recent deconvolution methods. AB - In a recent paper Vajda et al. presented a deconvolution method based on the assumptions that the response of a system and the input function to a system are described by first-order linear processes. The method is similar to one proposed by Veng-Pedersen, and obtains similar results. In this article a simpler, not new, and now generally available method for this special use is considered to point out potential risks associated with all three deconvolution methods. PMID- 2266501 TI - Quotations: borrowed ideas. PMID- 2266502 TI - Documentation of nursing care plans ... does not necessarily reflect quality in patient outcome. PMID- 2266503 TI - Postoperative urinary retention: Part II--A retrospective study. AB - Postoperative urinary retention, a potential postoperative complication, can lead to discomfort and contribute to atony of bladder wall, need for catheterization and, sometimes, prolonged hospital stays. A retrospective study was conducted to analyze variables related to postoperative urinary retention. Data was collected by a chart review of 100 postoperative cases in a large Veterans Administration Medical Center. All patients were male, had a mean age of 61.1 years, and had received spinal or general anesthesia. Patients with known urologic problems, paraplegic patients, quadruplegic patients, patients undergoing procedures lasting less than 3 hours, and patients with indwelling Foley catheters were excluded. The medical review form was used to collect data from the medical records. Sixty-one percent of the patients required straight catheterization for their first postoperative urinary output. Sixty-five percent of the spinal anesthetic patients and 57% of the general anesthetic patients required straight catheterization. Orthopedic patients were the highest percentage of patients requiring catheterization. The patients who received large volumes of intravenous (IV) fluid in the operating room were more likely to be catheterized in the PACU. Determining whether physical assessment or IV volume indicated need for catheterization of these patients was difficult because documentation on the PACU record was usually incomplete. Complete documentation of assessment and intervention on the PACU record occurred 10% of the time. A need for full assessment on all postsurgical patients in the PACU and improved documentation is indicated. PMID- 2266504 TI - Management of acute myocardial infarction in the postanesthesia care unit. AB - Surgery and anesthesia can compromise the delicate homeostasis between myocardial oxygen supply and demand in the patient with preexisting cardiac disease. This article identifies those patients at risk for developing a myocardial infarction. It also focuses on patient care assessment of the patient with chest pain in the PACU, and the implementation measures to manage chest pain and limit infarction size. PMID- 2266505 TI - An ambulatory approach to outpatient pediatric cardiac catheterization. AB - Outpatient procedures are growing rapidly in all health care facilities. Insurance companies, health maintenance organizations, and DRGs are dictating shorter lengths of stay in the hospital for cardiac catheterizations. An option for low-risk children with cardiac disease is outpatient cardiac catheterization. For a successful outpatient cardiac catheterization, an ambulatory program needs to be in place to provide an efficient, cost-effective, and caring environment for the child and family. With the expansion to the ambulatory setting, the clinical nurse's role and responsibilities have widened. Nursing assessment, intervention, and teaching is ongoing with specific standards in place to deliver quality patient care. Use of the outpatient setting will continue to increase and will accommodate patients cost effectively. The key to the success of the outpatient pediatric cardiac catheterization is to include the family in the health care team approach, which will result in quality patient care with high patient and family satisfaction. PMID- 2266506 TI - The athlete's knee. AB - The trend of the 1990s is for improved physical fitness with increased participation in exercise and sports. As a result, there has been an increased incidence in sport-related injuries with the knee being one of the most common areas affected. Ambulatory surgical centers can expect to see increasing numbers of arthroscopic knee surgeries. It is important for the nursing staff to understand the anatomy and physiology of the knee, nature of the injury, treatment, and discharge planning. PMID- 2266507 TI - Informed consent: how far must it go? AB - The case of the Mo cell line was the first to address the issue of ownership of human tissues removed during the course of surgery. It is also about the disclosure of sufficient information to enable "informed" consent for surgical or diagnostic procedures. Can patients have confidence when informed consent fails and conflict of interest may exist? In dealing with conflicting values, health care professionals must recognize that what may be immoral or unethical is not necessarily illegal. PMID- 2266508 TI - Criticism in perspective. PMID- 2266509 TI - Genetic and environmental effects on self-reported depressive symptoms in a general population twin sample. AB - To determine the etiology of self-reported depressive symptoms and their co occurrence in the general population, multivariate genetic models were fitted to the responses of 771 female twin pairs (463 MZ, 308 DZ) to a 20-item epidemiological depression inventory (CES-D scale). A model which contained one common genetic factor, one shared environmental factor, and four unique environmental factors provided a useful account of symptom covariation. Under this model, the four non-shared environmental factors explained the largest proportion of variance in response to the CES-D scale, whereas a single common genetic factor explained substantially less of the variation in symptomatology. Consistent with previous findings (Kendler, Heath, Martin, & Eaves, Archives of General Psychiatry 43, 213-221, 1986) shared environmental influences were found to play a relatively minor role in the report of depressive symptoms. These results suggest that while genetic factors do contribute to the covariation among symptoms of depression, it is the largely non-shared environmental factors that account for the co-occurrence of symptoms in the general population. PMID- 2266510 TI - Italian Multicentre Study on Dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease. AB - For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress. PMID- 2266511 TI - Diurnal variation in total plasma tryptophan in controls and in depression. AB - Circadian rhythms of total tryptophan were investigated by assays of hourly blood samples over 25 h. The study population consisted of four endogenously depressed patients investigated in the absence of any treatment and six healthy controls. The abnormalities detected by statistical analyses in untreated depression consisted mainly of amplitude reduction; the phase positions of the depressed patients were similar to those of the controls. PMID- 2266512 TI - Maternal expressed emotion and parental affective disorder: risk for childhood depressive disorder, substance abuse, or conduct disorder. AB - Expressed emotion (EE) refers to a set of emotional aspects of speech for which ratings have been derived. Seven independent studies have established that higher EE ratings in the relatives of patients with schizophrenia predict higher rates of relapse in these patients and two studies have established an association of higher EE in spouses with relapse of depression in their mate. There are no previous studies of parental EE as a predictor of childhood affective disorder or other disorders not in the schizophrenia spectrum. In this study we investigated the relationship between the level of maternal EE and the incidence of DSM-III affective disorder (major depression or mania or dysthymia), substance abuse, or conduct disorder in 273 children. We found that a higher degree of maternal expressed emotion was associated with a three-fold increase in a child's risk (odds multiplier) for having at least one of the following diagnoses: depressive disorder (major depression or dysthymia), substance abuse, or conduct disorder. This increased risk acts in addition to the increased risk of child diagnosis associated with parental affective illness. Research and clinical implications are discussed. PMID- 2266513 TI - Effects of social isolation on brain catecholamines and forced swimming in rats: prevention by antidepressant treatment. AB - Post-weaning rats were housed alone or in groups for a period of 4 or 8 weeks. A portion of the animals received tricyclic antidepressant treatment, desipramine 20 mg/kg/day, during this period. Animals were then tested behaviorally by forced swimming. Isolation was associated with significantly longer durations of immobility during forced swimming. This was blocked by desipramine treatment. Desipramine treatment did not have a significant effect on the swimming durations of group-housed rats. Hindbrain and midbrain levels of catecholamines were subsequently measured and turnover rates estimated by administration of alpha methyl-p-tyrosine or saline. Isolated rats had increased levels and decreased turnover of catecholamines. The increase in norepinephrine but not dopamine levels was blocked by desipramine, while antidepressant effects on turnover could not be tested with this method. Reduced social stimulation thus appears to be associated with reduced catecholamine release which may result in the accumulation of these transmitters in the central nervous system. Treatment with desipramine appeared essentially to compensate for reduced social stimulation, blocking isolation-induced noradrenergic neurochemical changes, while having few significant effects on control animals. This study may be helpful in furthering our understanding of how the interaction of organisms with their environment influence catecholamine systems and how antidepressants may act to restore function. PMID- 2266514 TI - Personality disorders in anorexia nervosa and bulimia nervosa. AB - Two self-report questionnaires (MCMI and BSI) designed to measure personality disorder (PD) according to DSM-III (R) criteria were administered to patients with a diagnosis of anorexia nervosa (AN) (n = 19), bulimia nervosa (BN) (n = 16), or both diagnoses (AN + BN) (n = 9), both before and after treatment for the eating disorder. The main finding was that self-reported Personality Disorder (PD) diagnoses are not stable enduring characteristics among this group of eating disorder patients. A high rate of PD diagnoses occurred in all patient groups at admission (93%) and at discharge (79%). Both MCMI and BSI scales were subject to significant change following treatment. A high prevalence of borderline personality disorder was found in patients with BN. Changes in depression and self-esteem scores correlated most strongly with changes in schizoid, schizotypal, histrionic and narcissistic scales. Assessment of PD using self report measures should be interpreted with caution in acutely symptomatic patients with eating disorders. PMID- 2266515 TI - Temporal clause comprehension in fluent and nonfluent aphasics. AB - Ten fluent and ten nonfluent aphasics participated in this study. Their ability to comprehend before and after clauses which mirrored the order of occurrence and those which did not mirror the order of events was investigated. Results indicate that type of aphasia was not a significant variable related to comprehension but that sentence type was a significant variable. Aphasics' comprehend before clauses better than after clauses. Nonfluent aphasics were able to comprehend those temporal clauses that mirror the order of occurrence better than those that do not. Order of mention was not a significant factor related to comprehension in the fluent group. PMID- 2266516 TI - [MRI in subacromial pathology. Report of 20 cases]. AB - The authors report the results of MRI performed in 20 patients presenting clinical symptoms of subacromial pathology. The MRI results are correlated to the results of arthrography or arthro CT scan and also to surgical results. MRI is an excellent technique if a precise protocol with T2 weighted images is respected in order to visualize tears or minor perforations of the supraspinatus muscle. PMID- 2266518 TI - [Splenic infarction in Plasmodium falciparum malarial attack]. AB - Splenic infarct during P. falciparum malaria is rare but well known. We report one case where ultrasonography and computed tomography suggested the diagnostic, showing respectively in splenic parenchyma a peripheral hypoechoic lesion and a low attenuation lesion. Diagnostic was confirmed by spontaneous regression during following days. We shall encounter more frequently than nowadays this rare entity due to expanding tourism and P. falciparum resistance. PMID- 2266517 TI - [Osteoarticular amyloidosis in hemodialyzed patients. Report of 4 cases]. AB - Chronic hemodialysis is sometimes complicated by an osteoarticular amyloidosis, which happens after a middle delay of ten years, it can be expressed by a tunnel carpal syndrome, a shoulder pariarthritis, bony cysts, and erosive spondylarthropathy. The authors reported their experience about four cases, and insisted on some evocatoring radiologic aspects. PMID- 2266519 TI - [The value of MRI in popliteal entrapment syndrome]. AB - The popliteal artery entrapment syndrome (PAES) is a frequent disease of especially young patients, often following a muscular exertion. To avoid the complications, the diagnosis must rapidly be done. According to this report of a 12 year old child, we think that magnetic resonance imaging (MRI) is very accurate to diagnose the abnormalities of the popliteal artery course, the muscular hypertrophies and can relieve of more invasive procedures such as the arteriography associated with known morbidity in young patients. PMID- 2266520 TI - [The blood-brain barrier]. AB - The blood-brain barrier (BBB) is present on three sites: the brain vessels, the choroid plexus and the arachnoid membrane. It is made of nonfenestrated endothelial or epithelial cells interconnected by tight junctions. Biochemically, the BBB is formed by bimolecular layers of phospholipids into which globular proteins are inserted. Exchanges through the BBB depend on whether the substances exchanged are soluble in water or in lipids. Hydrosoluble substances are largely excluded from the brain by the BBB; liposoluble substances pass the barrier easily by passive or active mechanisms. Water movements through the BBB are related to variations in osmolality. These data are of the utmost importance in all brain diseases with rupture of the BBB and in all neuroradiological procedures using contrast media. PMID- 2266521 TI - [Incidence of non-tumor anomalies of the facial sinuses on x-ray computed tomography of the brain of asymptomatic patients. Clinical and radiologic correlations between involvements of ethmoid cells and other sinus cavities]. AB - Two hundred ninety five consecutive brain CT examinations of asymptomatic adults were studied prospectively for detection of nontumoral paranasal sinus abnormalities. CT alterations were found in 104 cases (35.3%), localized to the ethmoid cells in 83 cases, the maxillary sinuses in 56 cases, the sphenoid sinuses in 19 cases, and the frontal sinuses in 18 cases. The relationships between ethmoid cells disease and alterations of the large paranasal cavities are analysed, and the association with previous sinusitis or rhinitis is evaluated. Frontal sinus disease is associated in more than two-thirds of the cases with pathologic meatic and/or unciform ethmoid cells, but such an association could not be demonstrated for the other cavities. PMID- 2266524 TI - The Defence Medical Services--how comprehensive? PMID- 2266522 TI - [Dura mater chondroma. A case report and review of the literature]. AB - Intradural chondromas are exceedingly rare intracranial tumors. We present a case of intradural chondroma. It is a clinical and radiological presentation, with special emphasis on CT appearance. The CT scan demonstrated a mass lesion with intratumors calcification areas, and slight enhancement after intravenous injection of contrast. The differential diagnosis with calcified meningioma is histological. PMID- 2266523 TI - [Tuberculous spondylitis with syndesmophytes and paraspinal ossification. Two case reports]. AB - The authors described 2 patients with spinal tuberculosis. The first one was presented with multiple anterior marginal involvement of vertebral bodies, centrosomatic spondylitis of L3, associated with a syndesmophytic showing spinal ossification. In the second case, spinal tuberculosis involved the vertebral arc of L2 and L4. A paravertebral ossification on both sides of L4 was seen. The nature of these vertebral and paravertebral ossifications was discussed. PMID- 2266525 TI - Armoured fighting vehicle injuries in peacetime. AB - A year-long prospective study of injuries caused by armoured fighting vehicles on exercises in West Germany revealed that 2 soldiers were killed. Another 41 needed hospital admission for treatment of injuries of the lower limb (16), upper limb (15), head (8) and back (2). Tank loader/signallers were peculiarly susceptible to severe leg injuries, due to the ankle being trapped and twisted by the turret rotating within the hull. Insecure, falling hatch covers accounted for many of the hand, head and back injuries. Soldiers in training need to be made more aware of these particular hazards. Reduced caution would make injuries such as these more common during armoured warfare, and their statistics should be included in casualty estimates. PMID- 2266526 TI - An investigation into regular recruit wastage from the British Army, 1988. AB - A study was made of recruit medical discharges in the British Army in 1988 with the aim of ascertaining the number of medical discharges amongst recruits. AFBs 6863 (Notification of Discharge of a Regular Recruit) were used as the source of data. Recruit medical wastage rate for 1988 was 897 cases, or 16.7% of all known discharges. Three types of medical discharges were present. Four hundred and ninety-six Type 1 or concealed discharges, (9.2% of discharges for all reasons) were made up of cases who had not been boarded and had mainly been discharged under QR 9.381 (defect of enlistment). Two hundred and seventy-five Type 2 discharges (5.1% of discharges for all reasons) represented boarded cases discharged under QR 9.385 (ceasing to fulfil medical requirements). One hundred and twenty-six Type 3 discharges (2.3% of all discharges) were boarded cases mainly discharged under QR 9.381 (defect of enlistment). As all discharges under paragraphs other than QR 9.385 are given administrative discharge outflow code, only the 275 Type 2 discharges (or 31.7% of medical discharges) appeared on the Army's own source of medical data, the TRIMEDS database. This had the effect of concealing the majority of those discharges caused by conditions predating enlistment therefore decreasing the number of known false negatives not detected at recruiting medicals. The biggest causes of discharge were conditions of the lower limbs and back (54.5% of medical discharges), a conglomerate of minor categories of pathology (14.6%), asthma (9.6%) and deformities (7.4%). Within each type the bulk of the discharges was concealed in Type 1 discharges especially for conditions predating enlistment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266527 TI - Cerebral cysticercosis as a common cause of epilepsy in Gurkhas in Hong Kong. AB - A prospective study of Nepalese adults (Gurkhas) based in Hong Kong who presented with adult-onset epileptiform seizures determined that cerebral cysticercosis was causative in 7 out of 8 cases. The relative roles of specific cysticercal serology and computerised axial tomography in diagnosis are discussed. Serum IgE levels were found to be raised in all patients with cerebral cysticercosis in the absence of other parasitic infection and reverted to normal after the patients were treated with praziquantel. Evidence suggests that the Gurkhas acquired their cysticercal infections in Nepal. PMID- 2266528 TI - Diabetes mellitus in the services--a review 1978-88. AB - The incidence of diabetes mellitus in the Services for 1978-88 is reviewed. Its influence on the Serviceman's career in the long and short term is discussed. Mortality and morbidity rates are low in the Services when compared with the general population, primarily because of the service demographic distribution. Problems with the discovery of asymptomatic diabetes and possible recommendations are discussed. PMID- 2266529 TI - Screening for squints and amblyopia in pre-school children in a service community. AB - A screening programme designed to detect visual defects in pre-school children was mounted in a Service community in West Germany. This showed the feasibility of screening and demonstrated that the results produced were superior to those of routine referral. The methods of findings are discussed. PMID- 2266530 TI - The introduction of a practice formulary in a military general practice. AB - Over a 15 month period, all the scripts written by doctors in the Episkopi Garrison Medical Centre, Cyprus, were analysed. A formulary was produced by using the most popular items in that 15 month period and tested in a one month trial period. The idea was to find a practical and efficient method of producing a 'basic' formulary to which items could be added or removed after discussion with colleagues. PMID- 2266531 TI - A review of obstetric epidural anaesthesia, British Military Hospital, Rinteln 1980-1985. AB - A retrospective study was undertaken of all epidurals inserted on the labour ward in BMH Rinteln from 1980 to 1985 inclusive, during which time both obstetricians and anaesthetists participated in providing an epidural service. It was impossible to show any difference between the expertise of anaesthetists and obstetricians in siting epidurals, when the incidence of complications or failed analgesia was compared. However, epidurals inserted by obstetricians were more likely to be converted to general anaesthetics for operative procedures than those inserted by anaesthetists, although no adequate explanation for this could be found. Given increasing patient demand for a 24-hour epidural service, and the logistic difficulties in Service hospitals of providing sufficient anaesthetic staff for this, obstetricians can be trained to help provide such a service. PMID- 2266532 TI - A case of military Munchausen's syndrome. AB - Since its initial description in 1951 many variants of Munchausen's Syndrome have been described. This present case report is of a patient who adopts military rank in order to gain admission to a service hospital: a case of Military Munchausen's Syndrome. PMID- 2266533 TI - Nosebleeds--the importance of taking a history. AB - Nosebleeds are exceedingly common, and usually idiopathic. Cautery under local anaesthetic to the vessels of the nasal septum is often used successfully as a treatment for the recurrent condition. However, rarely, a nosebleed may be a symptom of a more serious underlying disorder and a suitable history and examination are required. PMID- 2266534 TI - Reiter's disease: an historical review of a soldiers' disease. AB - Major conflicts in history have yielded an equal number of medical casualties as those injured in battle, and no more common a problem exists in the insanitary conditions of war as dysentery. The complication of arthritis following dysentery has been documented since ancient times, but it is not until the 16th Century that these cases appear in any numbers, and then it is predominantly in military personnel. "Reiter's Disease" is currently understood to mean an asymmetrical, predominantly lower-limb polyarthritis developing after urethritis (usually non gonococcal) or dysentery; conjunctivitis is not always a constant feature. This is the commonest inflammatory polyarthropathy of young men and both the epidemic (dysenteric) and sporadic (venereal) forms are historically prevalent in soldiers -a not surprising fact considering the squalor of war and the unrestrained behaviour of the Private soldier. This paper traces the history of Reiter's disease and highlights its affinity for military populations. PMID- 2266535 TI - Potential recruits in medical outpatients. PMID- 2266536 TI - A retrospective study of all low birth-weight preterm babies born in BMH Rinteln between 1980-1989. PMID- 2266537 TI - Estimation of cardiac output by bioimpedance cardiography. PMID- 2266538 TI - Development of antibodies for studying conceptus interferons in the cow. AB - Three synthetic peptides comprising amino acids 100-113, 131-140 and 152-172 of bovine trophoblast protein-1 (bTP-1) were synthesized, coupled to keyhole limpet hemocyanin and used for antibody production in rabbits. Of the resultant anti peptide antibodies, the antibody directed towards the C-terminal of bTP-1 (152 172) was found effective for recognizing native bTP-1 in enzyme-linked immunoabsorbent assay (ELISA), Western blotting and immunocytochemistry systems. By immunocytochemistry, anti-bTP-1(152-172) reacted with kidney and lung tissue, suggesting that the presence of other interferons in extra-embryonic tissues limits the specificity of the antibody. The other two anti-peptide antibodies showed low cross-reactivity to native bTP-1. None of the three peptides displayed antiviral activity or inhibited antiviral activity of bovine conceptus conditioned culture medium. Of other anti-interferon antibodies tested, antiserum to human interferon-alpha and bovine interferon-alpha I 1 showed only slight cross-reactivity with bTP-1 and trophoblast protein-1 (oTP-1). A monoclonal antibody raised against oTP-1 also recognized bTP-1 and bTP-1(152-172), suggesting that it recognizes an epitope on the C-terminal region of oTP-1 and bTP-1. In summary, the C-terminal region of bTP-1 is antigenic and accessible to antibodies. Thus, antibodies directed against this region should prove useful for immunochemical studies of bTP-1. PMID- 2266539 TI - Endocrine relationships of thymosin-alpha 1, thymosin-beta 4, and luteinizing hormone throughout the prepubertal period of development in heifers, ovariectomized heifers and ovariectomized heifers with estradiol implants. AB - To monitor the relationships of luteinizing hormone (LH) and thymosin-alpha 1 and -beta 4 in conjunction with possible gonadal feedback mechanisms that could alter thymic function (thymosin secretion), circulating thymosin-alpha 1 and -beta 4 and LH concentrations of control heifers (n = 6), ovariectomized heifers (n = 5) and ovariectomized heifers implanted with estradiol (n = 5) were determined during the prepubertal period (initiated at 266 days of age). Sequential blood samples were collected at 12-min intervals for 8 h before ovariectomy on day 0 and on days 8, 36, 50, 64, 78, 92, 106, 120 and 134 of the experiment. Thymosin beta 4 concentrations were not different between treatments. Thymosin-beta 4 concentrations gradually decreased until day 92 of the study, then increased two fold by day 134 of experimental sampling (400 days of age) when all control animals had attained puberty. Concentrations of thymosin-alpha 1 changed little as animals matured, but peak amplitude did increase over time (0.287 ng/ml at day 0 to 0.403 ng/ml at day 120; P less than 0.05). Mean concentration, number of episodic peaks and peak amplitude of thymosin-alpha 1 was increased in ovariectomized heifers in comparison to ovariectomized plus estradiol implants (P less than 0.05). Prior to cyclic ovarian function (prepuberty), changes in circulating thymosin-beta 4 concentrations seem to be independent of effects of gonadal steroids but thymosin-alpha 1 was responsive to estradiol. PMID- 2266540 TI - Transfer of susceptibility to experimental autoimmune orchitis from responder to non-responder substrains of BALB/c mice. AB - Substrains of BALB/c mice differ in their susceptibility to experimental autoimmune orchitis (EAO), with BALB/cJ representative of the non-responders and BALB/cBy representative of the responders. We examined whether the susceptibility of these two substrains could be altered by reciprocal adoptive transfer of lymphoid cells. The cells transferred were of three types, normal spleen cells, T cell-enriched spleen and lymph node cells from mice immunized with testis homogenate (TH) in complete Freund's adjuvant (CFA) and given an extract of Bordetella pertussis (BP) and the latter cells activated by in vitro culture with TH antigen for 48 h. Controls were given buffer alone. Cell or buffer recipients were immunized with TH + CFA + BP three weeks later and examined for testicular histopathology 25-28 days after immunization. The cultured, immune T-enriched cells were consistently effective in transferring susceptibility from BALB/cBy to BALB/cJ. In the reverse experiments, non-responsiveness could be transferred from BALB/cJs to BALB/cBys most effectively with immune, non-cultured T-enriched cells. Transfer of cultured, immune T-enriched cells from BALB/cJs to other BALB/cJs had no significant effect on susceptibility to EAO. The results suggest that susceptibility to EAO in BALB/c mice depends on the T cell responses in the mice and not on differences at the level of the testis. PMID- 2266541 TI - Humoral immune activity in CBA/Ca mice during late pregnancy and the post-partum period. AB - Syngeneically mated CBA/Ca mice were used to measure "spontaneous" immunoglobulin (Ig) secretion in the Peyer's patches (PP), spleen and the para-aortic lymph nodes (PALN), employing a protein A plaque assay, during the latter part of pregnancy and in the post-partum period. The lactating and non-lactating females were compared with respect to humoral immune activity (plaque-forming cells) and serum Ig levels (ELISA technique). The pregnancy-induced weight changes in some lymphoid organs and the elevation in the number of plaque-forming cells in spleen (IgG and IgM PFC), PALN (IgG and IgM PFC) and the PP (IgA PFC) lasted longer in the lactating than in the non-lactating mice (owing to hormonal differences). A very strong decrease in serum IgG was observed during pregnancy and after parturition IgG levels remained depressed longer in lactating than in non lactating mice. Interest has been focused on IgA in the study and this has been discussed as well as the possible reasons for the increased turnover of maternal serum Ig (especially IgG). PMID- 2266542 TI - Purification of bovine trophoblast protein-1 complex and quantification of its microheterogeneous variants as affected by culture conditions. AB - The bovine trophoblast protein-1 complex (bTP-1) is a group of glycosylated interferon-alpha 11, molecules secreted by the bovine conceptus that plays a critical role in preventing luteolysis during early pregnancy. In the current studies, secretion of individual variant forms of bTP-1 was quantified under a variety of culture conditions that could affect yields of bTP-1 for preparative scale production of bTP-1. Additionally, a purification scheme for bTP-1 was developed. Conceptuses from Day 17 produced 13 proteins in the molecular weight and pI range characteristic of bTP-1, with 4-5 isoforms (pI = 5.6-6.6) at each of three molecular weight classes (21, 23.2 and 25.8 kDa). The major forms of bTP-1 were two variants of 23.2 kDa having pIs of 6.2 and 6.6. The relative proportion of bTP-1 variants was generally unaffected by culture conditions. Cultured conceptuses secreted bTP-1 at a sustained rate for 3 days and gaseous environment was without major effect on bTP-1 secretion. Conceptuses from superovulated cows also produced bTP-1 at Day 17 of pregnancy, suggesting that superovulation might be a useful method for increasing total bTP-1 yield per cow. The purification scheme that was developed utilized ultrafiltration with Centricon devices to achieve rapid molecular weight fractionation, desalting and concentration of conceptus secretory proteins prior to purification of bTP-1 using anion-exchange and gel filtration HPLC. The resultant preparation of bTP-1 included 9 variant forms of bTP-1 as well as a slight amount of a 45-kDa contaminant. Purified bTP-1 possessed antiviral activity but the specific activity was apparently reduced when conceptus-conditioned medium used for purification was stored for prolonged periods. PMID- 2266543 TI - The influence of maternal humoral responsiveness on the specific immunocompetence of the progeny in mice. AB - The progeny of mice immunized during pregnancy with burro erythrocytes have an impaired ability to respond to that antigen. The suppression, which is shown to be of relatively short duration, lasting for between 8 and 12 weeks, is mediated by antibody transferred from mother to offspring via the milk, thus confirming the observations of previous workers. The experiments described in this paper show that passive immunization of the dams with "late" (greater than 200 days) low titre but high affinity antisera is as effective in feedback suppression as "early" (8-12 days) high titre but low affinity antisera. The high affinity antibodies in "late" antisera, like the low affinity antibodies of "early" antisera, are mainly transmitted via the milk and are apparently not, or are only minimally, transferred across the placenta. PMID- 2266544 TI - The nature of the neutral Na(+)-Cl- coupled entry at the apical membrane of rabbit gallbladder epithelium: III. Analysis of transports on membrane vesicles. AB - In rabbit gallbladder epithelium, a Na+/H+, Cl-/HCO3- double exchange and a Na(+) Cl- symport are both present, but experiments on intact tissue cannot resolve whether the two transport systems operate simultaneously. Thus, isolated apical plasma membrane vesicles were prepared. After preloading with Na+, injection into a sodium-free medium caused a stable intravesicular acidification (monitored with the acridine orange fluorescence quenching method) that was reversed by Na+ addition to the external solution. Although to a lesser extent, acidification took place also in experiments with an electric potential difference (PD) equal to 0. If a preset pH difference (delta pH) was imposed [( H+]in greater than [H+]out, PD = 0), the addition of Na-gluconate to the external solution caused delta pH dissipation at a rate that followed saturation kinetics. Amiloride (10( 4) M) reduced the delta pH dissipation rate. Taken together, these data indicate the presence of Na+ and H+ conductances in addition to an amiloride-sensitive, electroneutral Na+/H+ exchange. An inwardly directed [Cl-] gradient (PD = 0) did not induce intravesicular acidification. Therefore, in this preparation, there was no evidence for the presence of a Cl-/OH- exchange. When both [Na+] and [Cl-] gradients (outwardly directed, PD = 0) were present, fluorescence quenching reached a maximum 20-30 sec after vesicle injection and then quickly decreased. The decrease was not observed in the presence of a [Na+] gradient alone or the same [Na+] gradient with Cl- at equal concentrations at both sides. Similarly, the decrease was abolished in the presence of both Na+ and Cl- concentration gradients and hydrochlorothiazide (5 x 10(-4) M). The decrease was not influenced by an inhibitor of Cl-/OH- exchange (10(-4) M furosemide) or of Na(+)-K(+)-2Cl- symport (10(-5) M bumetanide). We conclude that a Na+/H+ exchange and a Na(+)-Cl- symport are present and act simultaneously. This suggests that in intact tissue the Na(+)-Cl- symport is also likely to work in parallel with the Na+/H+ exchange and does not represent an induced homeostatic reaction of the epithelium when Na+/H+ exchange is inhibited. PMID- 2266545 TI - Thiol-dependent passive K: Cl transport in sheep red blood cells: IX. Modulation by pH in the presence and absence of DIDS and the effect of NEM. AB - Recently we proposed that cytoplasmic acidification of low K+ (LK) sheep erythrocytes may stimulate ouabain-resistant Cl(-)-dependent K+ flux (K+: Cl- contransport), also known to be activated by cell swelling, treatment with N ethylmaleimide (NEM), or removal of cellular bivalent cations. Here we studied the dependence of K+ transport on intracellular and extracellular pH (pHi, pHo) varied either simultaneously or independently using the Cl-/HCO3- exchange inhibitor 4,4, diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In both control and NEM-treated LK cells volumes were kept near normal by varying extracellular sucrose. Using DIDS as an effective pH clamp, both K+ efflux and influx of Rb+ used as K+ congener were strongly activated at acid pHi and alkaline pHo. A small stimulation of K+ (Rb+) flux was also seen at acid pHi in the absence of DIDS, i.e., when pHi approximately pHo. Anti-Ll serum, known to inhibit K+: Cl-cotransport, prevented the pHi-stimulated K+ (Rb+) fluxes. Subsequent to NEM treatment at pH 6, K+ (Rb+) fluxes were activated only by raising pH, and thus were similar to the pH activation profile of K+ (Rb+) fluxes in DIDS-treated cells with pHo varied at constant physiologic pHi. Anti-Ll, which inhibited NEM-stimulated K+ (Rb+) fluxes, failed to do so in NEM-plus DIDS treated cells. Thus, NEM treatment interferes with the internal but not with the external pH-sensitive site. PMID- 2266546 TI - Thiol-dependent passive K: Cl transport in sheep red blood cells: X. A hydroxylamine-oxidation induced K: Cl flux blocked by diethylpyrocarbonate. AB - Hydroxylamine, a potent oxidizing agent used to reverse carbethoxylation of histidine by diethylpyrocarbonate, activated Cl-dependent K flux (K: Cl cotransport) of low K sheep red blood cells almost sixfold. When K: Cl cotransport was already stimulated by N-ethylmaleimide, hydroxylamine caused an additional twofold activation suggesting modification of sites different from those thiol alkylated. This conclusion was supported by the finding that hydroxylamine additively augmented also the diamide-induced K: Cl flux (Lauf, P.K. 1988. J. Membrane Biol. 101: 179-188) with dithiothreitol fully reversing the diamide but not the hydroxylamine effect. Stimulation of K: Cl cotransport by hydroxylamine was completely inhibited by treatment with diethylpyrocarbonate also known to prevent K: Cl cotransport stimulation by N-ethylmaleimide, both effects being independent of the order of addition. Hence, although the effect of carbethoxy modification of K: Cl flux cannot be reversed by hydroxylamine and thus excludes histidine as the target for diethylpyrocarbonate, our finding reveals an important chemical determinant of K: Cl cotransport stimulation by both hydroxylamine oxidation and thiol group alkylation. PMID- 2266548 TI - Gap junction formation and functional interaction between neonatal rat cardiocytes in culture: a correlative physiological and ultrastructural study. AB - The time course of gap junction formation and growth, following contraction synchronization of cardiac myocytes in culture, has been studied in a combined (electro) physiological and ultrastructural study. In cultures of collagenase dissociated neonatal rat cardiocytes, pairs of spontaneously beating myocytes synchronized their contractions within one beat interval within 2-20 min after they apparently had grown into contact. 45 sec after the first synchronized beat an appreciable junctional region containing several small gap junctions was already present. In the following 30 min, neither the area of individual gap junctions nor their total area increased. 75 min after synchronization both the area of individual gap junctions and their total area had increased by a factor of 10-15 with respect to what was found in the first half hour. In the period between 75 and 300 min again no further increase in gap junctional area was found. In double voltage-clamp experiments, gap junctions between well-coupled cells behaved like ohmic conductors. In poorly coupled cells, in which the number of functional gap-junctional channels was greatly reduced, the remaining channels showed voltage-dependent gating. Their single-channel conductance was 40-50 pS. The electrophysiologically measured junctional conductance agreed well with the conductance calculated from the morphometrically determined gap-junctional area. It is concluded that a rapid initial gap junction formation occurs during the 2 20 min period prior to synchronization by assembly of functional channels from existing channel precursors already present in the cell membranes. It then takes at least another 30 min before the gap-junctional area increases possibly by de novo synthesis or by recruitment from intracellular stores or from nonjunctional membranes, a process completed in the next 45 min. PMID- 2266547 TI - Pore formation by complement in the outer membrane of gram-negative bacteria studied with asymmetric planar lipopolysaccharide/phospholipid bilayers. AB - The interaction of complement with an asymmetric planar lipopolysaccharide/phospholipid bilayer system as a model for the lipid matrix of the outer membrane of Gram-negative bacteria has been studied. The addition of whole human serum to the aqueous solution at the lipopolysaccharide side of the asymmetric membrane resulted in a rapid increase of the bilayer conductance in discrete steps, indicating the formation of transmembrane pores, which were not observed in the case of pure phospholipid membranes. The amplitudes of the discrete conductance steps varied over a range of more than one order of magnitude. The mean single step conductance was (0.39 +/- 0.24) nS for a subphase containing (in mM): 100 KCl, 5 MgCl2 and 5 HEPES buffer. The steps were grouped into bursts of typically 9 +/- 3 events per burst and the conductance change within one burst was (8.25 +/- 4.00) nS. The pore-forming activity of serum at the asymmetric membrane system was independent of the presence of specific antibodies against the lipopolysaccharide but was dependent on calcium ions. Furthermore, the pore-forming activity required complement component C9. A model for the mode of pore formation by complement is proposed: The complement pore is generated in discrete steps by insertion of C9 monomers into the membrane and their irreversible aggregation to water-filled channels with a diameter of approximately 7 nm assuming a circular geometry. PMID- 2266549 TI - Psychotropic drugs and mental retardation: 1. Disabilities and the prescription of drugs for behaviour and for epilepsy in three residential settings. AB - The Birmingham Special Needs Register, a computerized database, was used to examine the disabilities of, and the use of psychoactive (psychotropic and antiepileptic) drugs among 1825 people over the age of 20 with mental retardation. People living in three different types of residential setting (hospitals, community residential facilities and family homes) were compared. The prevalence of physical disability, impaired communication and incontinence was highest among people resident in hospital, followed by those living with their families. People resident in community residential facilities were the least disabled group. Psychotropic drugs prescribed to alter behaviour were used most frequently in hospitals (prescribed for 40.2% of people), followed by community residential facilities (19.3%). Use was lowest in family homes (10.1%). Most hospital residents who received medication to alter behaviour did not have a diagnosed psychiatric disorder. The reported prevalence of behaviour disorders among the three populations was not significantly different. Drugs for epilepsy were prescribed for 26.2% of hospital residents, 9.3% of people in community residential facilities and 18.5% of people living with their families. PMID- 2266550 TI - Evaluation of a parent training programme for teaching mentally retarded children age-appropriate restaurant skills: a preliminary investigation. AB - A programme designed to train parents to teach their mentally retarded children age-appropriate restaurant skills was developed and evaluated. After participating in a brief training programme, three mothers attempted to facilitate greater independence in their developmentally delayed children during meals at a fast-food restaurant. The programme was evaluated by assessing the mothers' and children's performance in restaurants using a multiple-probe design. The results indicated that the parents' teaching interactions were influenced by the training programme and that their children's restaurant skills were enhanced. The results were discussed in the context of the normalization principle and deinstitutionalization movement. PMID- 2266551 TI - Contribution of ocular examination to the diagnosis of foetal alcohol syndrome in mentally retarded children. AB - An ophthalmological study was conducted on a series of 28 Swedish children suffering from mild mental retardation without an obvious aetiological diagnosis. The eye examination supported a diagnosis of foetal alcohol syndrome in five out of six suspected cases and revealed two additional not previously suspected (25%). Eye anomalies were observed in 16 patients (57%) with fundus abnormalities (optic nerve hypoplasia, retinal dystrophy) being most frequent, occurring in 11 cases (39%). Four patients had substantially reduced visual acuity in both eyes. Eight children had abnormal features of the face and outer eye region. Ocular motility disturbances (strabismus or nystagmus) were seen in five patients. The ophthalmological study disclosed that at least 10% of this group of children with mild mental retardation suffered from the foetal alcohol syndrome. It is concluded that, in children with mental retardation, an ocular examination is a valuable diagnostic tool for revealing prenatal origin. PMID- 2266552 TI - Inhalation of a drawing pin: an unusual hazard of smoking in the mentally handicapped. AB - The case of a mildly handicapped man who inhaled a drawing pin is described. Early chest radiology is recommended in unexplained respiratory symptoms in mental handicap. PMID- 2266553 TI - X-ray analyses of aspartic proteinases. III Three-dimensional structure of endothiapepsin complexed with a transition-state isostere inhibitor of renin at 1.6 A resolution. AB - The aspartic proteinase, endothiapepsin (EC 3.4.23.6), was complexed with a highly potent renin inhibitor, H-261 (t-Boc-His-Pro-Phe-His-LeuOHVal-Ile-His), where OH denotes a hydroxyethylene (-(S) CHOH-CH2-) transition-state isostere in the scissile bond surrogate. Crystals were grown in a form that has the same space group P2(1) as the uncomplexed enzyme, but with a 10 A decrease in the length of the alpha-axis and a 13 degrees decrease in the beta-angle. X-ray data have been collected to a resolution of 1.6 A. The rotation and translation parameters defining the position of the enzyme in the unit cell were determined previously using another enzyme-inhibitor complex that crystallized isomorphously with that of H-261. The molecule was refined using restrained least-squares refinement and the positions of non-hydrogen atoms of the inhibitor and water molecules were defined by difference Fourier techniques. The enzyme-inhibitor complex and 322 water molecules were further refined to a crystallographic R factor of 0.14. Apart from a small rigid group rotation of a domain comprising residues 190 to 302 and small movements in the flap, there is little difference in conformation between the complexed and uncomplexed forms of the enzyme. The inhibitor is bound in an extended conformation along the active site cleft, and the hydroxyl group of the hydroxyethylene moiety is hydrogen-bonded to both catalytic aspartate carboxylates. The complex is stabilized by hydrogen bonds between the main-chain of the inhibitor and the enzyme. All side-chains of the inhibitor are in van der Waals' contact with groups in the enzyme and define a series of specificity pockets along the active site cleft. The study provides useful clues as to how this potent renin inhibitor (IC50 value of 0.7 x 10(-9) M) may bind renin. In particular it defines the interactions of the hydroxyethylene transition-state isostere with the enzyme more precisely than has been previously possible and therefore provides a useful insight into interactions in the transition state complex. PMID- 2266554 TI - Strength and co-operativity of contributions of surface salt bridges to protein stability. AB - Many of the interactions that stabilize proteins are co-operative and cannot be reduced to a sum of pairwise interactions. Such interactions may be analysed by protein engineering methods using multiple thermodynamic cycles comprising wild type protein and all combinations of mutants in the interacting residues. There is a triad of charged residues on the surface of barnase, comprising residues Asp8, Asp12 and Arg110, that interact by forming two exposed salt bridges. The three residues have been mutated to alanine to give all the single, double and triple mutants. The free energies of unfolding of wild-type and the seven mutant proteins have been determined and the results analysed to give the contributions of the residues in the two salt bridges to protein stability. It is possible to isolate the energies of forming the salt bridges relative to the solvation of the separated ions by water. In the intact triad, the apparent contribution to the stabilization energy of the protein of the salt bridge between Asp12 and Arg110 is -1.25 kcal mol-1, whereas that of the salt bridge between Asp8 with Arg110 is 0.98 kcal mol-1. The strengths of the two salt bridges are coupled: the energy of each is reduced by 0.77 kcal mol-1 when the other is absent. The salt-linked triad, relative to alanine residues at the same positions, does not contribute to the stability of the protein since the favourable interactions of the salt bridges are more than offset by other electrostatic and non-electrostatic energy terms. Salt-linked triads occur in other proteins, for example, haemoglobin, where the energy of only the salt-bridge term is important and so the coupling of salt bridges could be of general importance to the stability and function of proteins. PMID- 2266555 TI - A precise analytical method for calculating the electrostatic energy of macromolecules in aqueous solution. AB - A new method for calculating the total electrostatic free energy of a macromolecule in solution is presented. It is applicable to molecules of arbitrary shape and size, including membranes or macromolecular assemblies with substrate molecules and ions. The method is derived from integrating the energy density of the electrostatic field and is termed the field energy method. It is based on the dielectric model, in which the solute and the surrounding water are regarded as different continuous dielectrics. The field energy method yields both the interaction energy between all charge pairs and the self energy of single charges, effectively accounting for the interaction with water. First, the dielectric boundary and mirror charges are determined for all charges of the solute. The energy is then given as a simple function of the interatomic distances, and the standard atomic partial charges and volumes. The interaction and self energy are shown to result from three-body and pairwise interactions. Both energy terms explicitly involve apolar atoms, revealing that apolar groups are also subject to electrostatic forces. We applied the field energy method to a spherical model protein. Comparison with the Kirkwood solution shows that errors are within a small percentage. As a further test, the field energy method was used to calculate the electrostatic potential of the protein superoxide dismutase. We obtained good agreement with the result from a program that implements the numerical finite difference algorithm. The field energy method provides a basis for energy minimization and dynamics programs that account for the solvent and screening effect of water at little computational expense. PMID- 2266556 TI - Analysis of the gel electrophoresis of looped protein-DNA complexes by computer simulation. AB - The theory of mass transport coupled to reversible interactions under chemical kinetic control forms the basis of a numerical model that has been applied to systems such as lac repressor-lac operator DNA, in which a protein binds in two different modes to linear DNA carrying two specific binding sites. Three complexes may be formed: (1) a linear 1:1 complex with one protein molecule bound to one site on the DNA molecule; (2) a 1:1 complex in which a single protein molecule is bound to both sites simultaneously, thereby inducing a large DNA loop; and (3) a 2:1 linear complex in which two protein molecules are bound in tandem, each occupying a single site. The computational model affords a quantitative numerical simulation of the observed gel electrophoretic patterns produced by titration of the DNA with protein and provides new insights into the shape and nature of the patterns. In particular, the patterns may represent unimodal or bimodal reaction zones. Nevertheless, analysis of the peaks in the patterns obtained at low DNA and high protein concentration provides essential information as to the stoichiometry of the complexes and satisfactory estimates of association constants. The theory thus provides the experimenter with guidelines for quantitative evaluation of the results of gel retardation assays of the particular system under investigation, once protein-induced DNA (or RNA) loops have been established by independent physical or chemical methods. It is suggested that these insights might also find application to systems involving the binding of two or three different proteins to DNA with loop formation. PMID- 2266557 TI - Effect of protons on the amidase activity of human alpha-thrombin. Analysis in terms of a general linkage scheme. AB - The amidase activity of human alpha-thrombin has been studied in the pH range 5.5 to 10, and at four different chloride concentrations from 5 mM to 1 M. The Michaelis-Menten constant, Km, shows a bell-shaped dependence over the pH range studied, with a minimum around pH 8. The pH dependence of the catalytic constant, kcat, shows multiple inflection points especially at low (less than 0.1 M) chloride concentrations, thereby implicating the existence of multiple catalytic forms of the enzyme. A general linkage scheme is proposed for the analysis of the effect of protons on thrombin amidase activity, and experimental data have globally been analysed over the entire pH range in terms of such a scheme. Four proton-linked ionizable groups seem to be involved in the control of thrombin amidase activity. Two of these groups change their pK value upon substrate binding to the enzyme and account for the pH dependence of Km. All four groups control the catalytic activity of the enzyme which decreases with increasing protonation. Chloride has little effect on Km, while kcat changes significantly at pH less than 8. This effect is due to an increased enzymatic activity of the highly protonated intermediates at high chloride concentrations, as well as to the pK shift of two proton-linked ionizable groups. PMID- 2266558 TI - Crystallization and preliminary X-ray analysis of two different forms of mitochondrial creatine kinase from chicken cardiac muscle. AB - Crystals of mitochondrial creatine kinase isolated from chicken heart were grown by precipitation with polyethylene glycol 1000. The enzyme has been crystallized in the absence and presence of ATP in two different space groups. Crystals are tetragonal, with space group P42(1)2, a = b = 171 A, c = 150 A in the absence of ATP; and P422, a = b = 101 A, c = 114.4 A in the presence of ATP. We suggest that there is one octamer (346 kDa) per asymmetric unit without ATP and one dimer (86 kDa) per asymmetric unit with ATP. Using synchrotron radiation, the octameric form diffracts to at least 3 A resolution. PMID- 2266559 TI - DNA specificity of the Cre recombinase resides in the 25 kDa carboxyl domain of the protein. AB - The Cre protein of bacteriophage P1 is a 38.5 kDa site-specific recombinase that belongs to the Int family of recombination proteins. Cre acts by binding specifically to a 34 base-pair sequence, lox, where it carries out recombination. A limited chymotryptic digest of Cre resulted in two fragments of sizes 25 and 13.5 kDa, respectively. The sequence of the amino terminus of the purified 25 kDa peptide demonstrates that this peptide represents the carboxyl-terminal portion of the Cre protein. A truncated version of the cre gene was constructed which produces only the 25 kDa peptide. The 25 kDa peptide is capable of specific binding to the lox site, but binds at lower affinity than does wild-type Cre. Footprinting with Fe-EDTA indicates that the 25 kDa peptide protects the inverted repeats of the lox site but shows only partial protection of the spacer region. This is in contrast to the footprint obtained with wild-type Cre which protects the entire spacer region. PMID- 2266560 TI - Structure and function of X-Pro dipeptide repeats in the TonB proteins of Salmonella typhimurium and Escherichia coli. AB - The TonB protein is required for several outer membrane transport processes in bacteria. A short 33-residue peptide segment of TonB has been studied by 1H and 13C nuclear magnetic resonance spectroscopy. The sequence of this peptide segment contains multiple Glu-Pro and Lys-Pro dipeptide repeats that maintain rigid, elongated structures and flank a short connecting segment that adopts a beta strand configuration. This TonB peptide is shown to interact specifically with the FhuA protein, the outer membrane receptor for ferrichrome-iron, providing the first direct evidence that the TonB protein interacts with outer membrane receptors. Interaction with the FhuA protein involves the extended structural element containing positively charged Lys-Pro repeats, and suggests a functional role for this segment of the TonB protein. As TonB is anchored in the cytoplasmic membrane the protein must, uniquely, span the periplasm. These data, together with studies described in the accompanying paper, suggest a model by which TonB serves to transduce conformational information over extended distances, from the cytoplasmic membrane to the outer membrane. PMID- 2266561 TI - TonB protein of Salmonella typhimurium. A model for signal transduction between membranes. AB - The tonB gene product is required for several outer membrane transport processes in bacteria. The tonB gene from Salmonella typhimurium was sequenced and found to be similar to that of Escherichia coli. The TonB protein is highly proline-rich and includes an unusual segment consisting of multiple X-Pro dipeptide repeats. A synthetic peptide corresponding to this segment has been used to raise anti-TonB antibodies. TonB was shown to be associated with the cytoplasmic membrane, apparently anchored via a single hydrophobic N-terminal segment. Protease accessibility studies, and the use of a series of TonB-beta-lactamase fusions, showed that the rest of the TonB protein is periplasmic. Unusually, export of TonB is not accompanied by cleavage of the N-terminal signal peptide. In the accompanying paper, we show that TonB interacts directly with the outer membrane FhuA (TonA) receptor. Thus, TonB must span the periplasm, providing a link between the cytoplasmic membrane and receptors in the outer membrane. On the basis of these data, and those published by other laboratories, we propose a model whereby TonB serves as a "mechanical" linkage that, by transmitting protein conformational changes from the cytoplasmic membrane across the periplasm, acts as a means of coupling energy to outer membrane transport processes. Such a mechanism has general implications for signal transduction within and between proteins. PMID- 2266562 TI - Bacteriophage T7 DNA packaging. I. Plasmids containing a T7 replication origin and the T7 concatemer junction are packaged into transducing particles during phage infection. AB - Bacteriophage T7 DNA is a linear duplex molecule with a 160 base-pair direct repeat (terminal redundancy) at its ends. During replication, large DNA concatemers are formed, which are multimers of the T7 genome linked head to tail through recombination at the terminal redundancy. We define the sequence that results from this recombination, a mature right end joined to the left end of T7 DNA, as the concatemer junction. To study the processing and packaging of T7 concatemers into phage particles, we have cloned the T7 concatemer junction into a plasmid vector. This plasmid is efficiently (at least 15 particles/infected cell) packaged into transducing particles during a T7 infection. These transducing particles can be separated from T7 phage by sedimentation to equilibrium in CsCl. The packaged plasmid DNA is a linear concatemer of about 40 x 10(3) base-pairs with ends at the expected T7 DNA sequences. Thus, the T7 concatemer junction sequence on the plasmid is recognized for processing and packaging by the phage system. We have identified a T7 DNA replication origin near the right end of the T7 genome that is necessary for efficient plasmid packaging. The origin, which is associated with a T7 RNA polymerase promoter, causes amplification of the plasmid DNA during T7 infection. The amplified plasmid DNA sediments very rapidly and contains large concatemers, which are expected to be good substrates for the packaging reaction. When cloned in pBR322, a sequence containing only the mature right end of T7 DNA is sufficient for efficient packaging. Since this sequence does not contain DNA to the right of the site where a mature T7 right end is formed, it was expected that right ends would not form on this DNA. In fact, with this plasmid the right end does not form at the normal T7 sequence but is instead formed within the vector. Apparently, the T7 packaging system can also recognize a site in pBR322 DNA to produce an end for packaging. This site is not recognized solely by a "headful" mechanism, since there can be considerable variation in the amount of DNA packaged (32 x 10(3) to 42 x 10(3) base-pairs). Furthermore, deletion of this region from the vector DNA prevents packaging of the plasmid. The end that is formed in vector DNA is somewhat heterogeneous. About one-third of the ends are at a unique site (nucleotide 1712 of pBR322), which is followed by the sequence 5'-ATCTGT-3'. This sequence is also found adjacent to the cut made in a T7 DNA concatemer to produce a normal T7 right end. PMID- 2266563 TI - Bacteriophage T7 DNA packaging. II. Analysis of the DNA sequences required for packaging using a plasmid transduction assay. AB - Recombinant plasmids carrying a bacteriophage T7 origin of DNA replication and sequences from the T7 concatemer junction are efficiently packaged into transducing particles during phage infection. With some constructs, as many as 50 transducing particles are produced per infected cell. We have used this plasmid packaging system to determine which T7 DNA sequences are required for the processing and packaging of the plasmid concatemers and to investigate the effects of altering the spacing and orientation of the required sequences. An origin of T7 DNA replication is essential for high-efficiency transduction, presumably to form the plasmid concatemers that are the substrates of the packaging reaction. In addition, two short sequences from the concatemer junction are required, one flanking the site where the right end of T7 DNA is formed (pacR) and the other flanking the site for formation of the left end (pacL). The spacing between pacR and pacL is not important, but the sequences must be positioned in the same orientation on the plasmid. With certain deletions of pacL, the specificity of end formation is reduced but the efficiency of packaging is near normal. Plasmids that contain only one of the two pac sites are packaged at about 10% of the efficiency of those with both sites. The residual packaging of these plasmids results from regeneration of the other packaging site by recombination with T7 phage DNA. To function in plasmid packaging, the sequences from the concatemer junction must be positioned on the plasmid in the same orientation relative to the T7 replication origin as is found in T7 DNA. This apparently results from a requirement for transcription through these sequences in the rightward direction from the T7 promoter that is associated with the replication origin. Such transcription from another T7 promoter (phi 10), that is not itself a replication origin, allows packaging when the origin is in the opposite orientation. PMID- 2266564 TI - Bacteriophage T7 DNA packaging. III. A "hairpin" end formed on T7 concatemers may be an intermediate in the processing reaction. AB - An unusual left end (M-end) has been identified on bacteriophage T7 DNA isolated from T7-infected cells. This end has a "hairpin" structure and is formed at a short inverted repeat sequence centered around nucleotide 39,587 of T7, 190 base pairs to the left of the site where a mature left end is formed on the T7 concatemer. We do not detect the companion right end that would be formed if the M-end is produced by a double-stranded cut on the T7 concatemer. This suggests that the hairpin left end may be generated from a single-stranded cut in the DNA that is used to prime rightward DNA synthesis. The formation of M-end does not require the products of T7 genes 10, 18 or 19, proteins that are essential for the formation of mature T7 ends. During infection with a T7 gene 3 (endonuclease) mutant, phage DNA synthesis is reduced and the concatemers are not processed into unit length DNA molecules, but both M-end and the mature right end are formed on the concatemer DNA. These two ends are also found associated with the large, rapidly sedimenting concatemers formed during a normal T7 infection while the mature left end is present only on unit length T7 DNA molecules. We propose that DNA replication primed from the hairpin end produced by a nick in the inverted repeat sequence provides a mechanism to duplicate the terminal repeat before DNA packaging. Packaging is initiated with the formation of a mature right end on the branched concatemer and, as the phage head is filled, the T7 gene 3 endonuclease may be required to trim the replication forks from the DNA. Concatemer processing is completed by the removal of the 190 base-pair hairpin end to produce the mature left end. PMID- 2266565 TI - RecA protein self-assembly. II. Analytical equilibrium ultracentrifugation studies of the entropy-driven self-association of RecA. AB - We have investigated the self-association of RecA protein from Escherichia coli by equilibrium ultracentrifugation. Monomeric RecA (Mr = 37,842) was observed in reversible equilibrium with trimers, hexamers and dodecamers in the presence of 1.5 M-KCl, 5 mM-Hepes, 1 mM-EDTA, 2 mM-ATP (pH 7.0) at 1 degrees C. The equilibrium was strongly temperature-dependent, with polymerization being favored as the temperature was raised from 1 degrees C 21 degrees C, and was reversible with respect to temperature. The values of both the standard enthalpy and entropy of self-association were positive, indicating that it is an entropy-driven process under these conditions. In the absence of KCl, in 50 mM-citrate, 5 mM ATP, 5% (v/v) glycerol (pH 6.0) at 4 degrees C, only small amounts of RecA monomer could be detected, while in 10 mM-Tris-acetate, 10% glycerol (pH 7.5) at 4 degrees C, the smallest species present in significant concentration appeared to be the trimer. The majority of the species observed had molecular weights between 228,000 and 456,000, suggesting dominant stoichiometries of six to 12 monomers per oligomer. At pH 6.0, in the absence of ATP, much larger oligomers containing at least 24 monomers also appeared to be present. The data are consistent with an equilibrium mixture of monomers, trimers, hexamers, dodecamers, 24-mers and higher oligomers, with the distribution of oligomers being dependent on solution conditions. Thermodynamic analysis indicates that these oligomeric species are in reversible equilibrium with each other. It is not certain whether trimers assemble directly into hexamers, or whether disassembly into monomers is a prerequisite for the formation of higher oligomers. The possible role of higher-order RecA oligomers in the formation of RecA nucleoprotein filaments is discussed. PMID- 2266566 TI - Modeling of globular proteins. A distance-based data search procedure for the construction of insertion/deletion regions and Pro----non-Pro mutations. AB - A distance-based database search scheme is proposed for modeling Pro----in non Pro and insertion/deletion regions of homologous globular proteins up to six residues in length. In the first step, geometric descriptors, the number of residues involved and target distances corresponding to the separation of C alpha atom positions adjacent to the "missing" segment, are chosen. In the second step, a database of high-resolution X-ray structures is scanned for segments with similar descriptors and selected segments are binned according to conformational type. In the third and fourth steps, the selected conformations are docked into the protein, and geometric and energetic criteria are used to determine their viability as segment models. The fifth step consists of an interaction scheme in which the geometric descriptors are redefined. This compensates for the use of a limited database and/or for the use of a poor original protein model adjacent to the missing segment. The procedure has been tested on Pro----non-Pro mutations in the homologous proteins penicillopepsin and endothiapepsin, and on the insertion/deletion regions of the homologs penicillopepsin and endothiapepsin, trypsin and gamma-chymotrypsin and hen and human lysozyme. The test cases represent a wide variety of secondary structural elements (helix, sheet, turn and coil) and insertion/deletion lengths (0 to 4 residues). It is shown that 79% of the test cases are accurately modeled (within 0.54 A root-mean-square (r.m.s.) deviation for main-chain atoms) using the proposed scheme. Failure of the scheme (main-chain atom r.m.s. deviations greater than 1.29 A) in 21% of the cases appears to be related to the presence of infrequently observed conformations or locally unique folds of the target proteins with respect to the database (18% of the test cases); the remaining 3% are unexplained. Geometric and energetic criteria are able to discriminate between trial conformations that correspond to the X-ray structures and those that are different in 97% of the conformations generated by the distance-weighted database search scheme. The scheme is shown to be relatively insensitive to uncertainty in the template co-ordinates, since the geometric descriptors were taken from the homologous protein (r.m.s. deviations in the position of descriptors range from 0.18 to 1.35 A for the accurately modeled test cases). It is demonstrated that the scheme can be used to correct local sequence misalignments. PMID- 2266567 TI - [Study on the effect of various conditions and age to blood platelet aggregation test]. AB - The result of the platelet aggregation test was affected by various conditions. We performed the platelet aggregation test by changing different conditions, including: 1. adding different anticoagulants 2. interval between sampling and standing 3. platelet count 4. the concentrations of different reagents (ADP, Epinephrine and Collagen) respectively and the aggregation rate of blood platelet were compared among different age groups. The best condition for platelet aggregation rate was obtained as follows: 1) Citric acid of 3.8% is the best anticoagulant. 2) Test should be completed within 4 hours upon sample collection. 3) The optimal incubation temperature is between 25 degrees to 37 degrees C. 4) Platelet count of 2 to 4 x 10(5)/microliters gives the most constant result. 5) The optimal concentration for working solution of ADP, collagen and Epinephrine are 5.0 microns, 5.0 micrograms/ml and 50 microM respectively. 6) The aggregation rate of blood platelet increases with age. PMID- 2266568 TI - Abdominal sonographic screening in a single community. AB - A health survey, on adults aged 30 years or more, was carried out at 3 villages on the southwest coast of Taiwan. A total of 923 cases (42.6%) of the 2,166 population participated in the survey. The estimated total population prevalence rates were as follows: no gross lesion (60.5%), fatty liver (25.2%), biliary stone (5.2%), gall bladder polyp (1.9%), hepatic hemangioma (1.4%), liver cyst (0.9%) and renal cyst (2.9%). The prevalence rates of gall bladder polyp and renal cyst were higher in men, while that of fatty liver was higher in women. There was an increase in the prevalence with age for fatty liver in females. The results might be a reference about the above findings among Chinese in Taiwan. PMID- 2266569 TI - Consecutive examinations by scotch-tape perianal swabs in diagnosis of enterobiasis. AB - In order to determine how many consecutive perianal examinations can increase the accuracy of the diagnosis of enterobiasis, nursery and kindergarten children were examined with 8 consecutive scotch-tape perianal swabs. Primary school students were examined with 4 consecutive swabs, while junior high school students were examined with one swab in the morning and another in the afternoon. The positive rates among nursery and kindergarten children increased from 17.3% and 34.6% by a single swab to 44.4% and 70.2% by 8 consecutive swabs respectively. Significant differences in rates among kindergarten children by class were found by 4 to 8 swabs (3rd year class 65.6-78.7%, 2nd year class 50.3-61.1%, 1st year class 52.3 69.5%). The rate among primary school students increased from 59.9% by a swab to 77.3% by 4 consecutive swabs. Significant differences were found among the rates by grade. The highest was detected in grade 3 and lowest in grade 6. There was no significant difference between the positive rates among junior high school students obtained in the morning (33.7%) and in the afternoon (31.3%), and also no significant difference among rates by junior school was found. There was no significant difference between positive rates by sex in kindergarten children (boys, 68.8%, girls, 71.9%) and primary school students (boys, 76.8%; girls, 77.9%). However, the positive rate of junior high school girls (47.3%) was significantly higher than that of junior high school boys (37.4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266570 TI - [Sinus tracts of dental origin. A clinical study. Part I]. AB - Chronic draining sinus tracts on the oral mucosa or the skin of the face frequently have dental pathosis. The purpose of this study was to investigate the incidence and the distribution of age, sex, opening, and tooth position of sinus tract cases with dental origin. A total of 678 teeth requiring endodontic treatment and having periapical pathosis at the Department of Conservative Dentistry, Kaohsiung Medical College Hospital, were studied. There were 86 (12.7%) teeth associated with sinus tracts, among these 47 (16.3%, 47/288) were from males and 39 (10.0%, 39/390) were from females. Of the openings of the sinus tracts, 70 were on the facial, 2 were on the palatal, 1 was on the distal, 4 were on the lingual, 2 were on both facial and lingual surfaces of teeth, and 7 were extraorally. The sinus tracts occurred more frequently in the mandibular than maxillary teeth. The maximum number of 34 cases (39.5%, 34/86) were from the 21 30 years of age group. In addition, we also found that the teeth with periapical lesions of larger than 5 mm in diameter are more frequently associated with sinus tracts than those teeth with lesions of smaller than 5 mm in diameter. PMID- 2266571 TI - [Use of silicone template to prepare guide planes for removable partial denture]. AB - Guide planes are used not only for one path of insertion and removal but also to increase both the stability of the denture and resistance to lateral movement; they also protect the abutments from displacement during insertion and removal of the denture. Therefore, it is necessary to give attention to this part of the mouth preparation in the construction of removable partial dentures. Some methods have developed to form exact guide planes. They are the free-hand method, the modeling plastic index, the acrylic index, the laboratory milling technique, and the intraoral parallelism device. However, most of these instruments are either too expensive or too sophisticated to be considered practical for removable partial denture preparations. This article describes a simple and effective method to assure the development of guide planes intraorally as they are planned on the diagnostic cast. The occlusal or incisal surface of the abutment on the prepared stone cast was completely covered with a newly mixed putty type silicone rubber base. The plastic silicone was put against the prepared guide plane on the stone cast and was compressed with a blockout trimmer held on the surveyor before the silicone setting. All of the prepared guide plane was contoured to disclose the marker and to form a ledge. After the silicone setting, the template was removed and trimmed so that soft tissue will not interfere with the intraoral reorientation. As the templates are placed on the abutments intraorally, the abutments bulging out of the template area are obviously discernible and prepared guide planes on the diagnostic cast can be easily and definitely duplicated on the abutments. PMID- 2266572 TI - [Relationship between baccalaureate nursing faculty's competence and satisfaction with job and environment]. AB - The major purpose of this study is to understand the baccalaureate nursing faculty's competence and their satisfaction with their job and environment. There are ninety six baccalaureate nursing faculty members who are teaching in undergraduate programs and hold Bachelor's degrees. They were investigated by answering a questionnaire which was then analyzed. The majority of nursing faculty members (51.2%) held Master degrees, while 48.8% held Bachelor degrees in nursing. There were 45.2% of the instructors and associate professors who were not held. There were 34.1% faculty members that felt full of hope about the future. Half of the samples stated that their desires were consistent with the job and felt that they were successful in their job. The majority of samples 51.2% felt satisfied with their present jobs. Only 46.3% of the nursing faculty members felt that they could develop their talent to the fullest. The variables in teachers' competence such as: age, clinical experience, rank, job satisfaction, job desire, and talent development are significantly different in scores of the satisfaction with job and environment. Job satisfaction, job desire, and academic rank could predict the nursing faculty's overall satisfaction with their jobs. PMID- 2266573 TI - Left paraduodenal hernia complicating pregnancy--a case report. AB - A pregnant woman with intestinal obstruction due to left paraduodenal hernia is described. To the authors' knowledge, this paper represents the first case of left paraduodenal hernia complicating pregnancy. Paraduodenal hernia is a congenital anomaly where the small intestine is trapped. The enlarging uterus distorts the hernial sac, and converts a partial obstruction into a complete one. The pathogenesis and management of this rare case is discussed. PMID- 2266574 TI - Conduction through the reentrant circuit in recurrent sustained ventricular tachycardia evaluated by use of transient entrainment. AB - Using transient entrainment, the effect of the paced cycle length on the conduction through the reentrant circuit was assessed in recurrent sustained ventricular tachycardia (VT). Fourteen patients were included in the present study and their VTs were paced at multiple cycle lengths while the criteria of entrainment were confirmed at each paced cycle length. Then, the effect of the paced cycle length upon the conduction time, which was evaluated by the measurement of the time interval from stimulus to the entrained electrogram, was analyzed. In the overdrive pacings of VT, 3 response patterns in conduction time were observed: an increasing pattern (n = 8), a flat pattern (n = 5) and a decreasing pattern (n = 1) while the local conduction time outside the reentrant circuit remained unchanged at comparable paced cycle lengths. A decremental property is the likely mechanism responsible for the paced cycle length-dependent prolongation. As for the flat pattern, the existence of a fully excitable gap may be responsible. A paced cycle length related change in the reentrant circuit may account for the decreasing pattern. By using transient entrainment, the electrophysiological characteristics of the reentrant circuit can be evaluated and the information so gathered may be valuable in analyzing the action of antiarrhythmic drugs on the slow pathway. PMID- 2266575 TI - Evolution of right bundle branch block and other intraventricular conduction abnormalities in the transplanted human heart. AB - We performed 12-lead electrocardiography (ECG) repeatedly in 13 patients with cardiac transplants. QRS block occurred at some point in 12 patients and its course was either sporadic, progressive, persistent or fluctuating (5, 3, 3 and 1 patient (s), respectively). In the first postoperative week, complete or incomplete right bundle branch block (RBBB) occurred in 10 patients. Left anterior fascicular block also occurred in 3 of the 10 patients. However, the block(s) subsided within 1 month in the 3 and 2 more patients. Nonspecific block, isolated left anterior fascicular block and left bundle branch block also occurred occasionally. QRS block was unrelated to the occurrence of cardiac rejection, catheter injury, right ventricular pressure or volume overloading, left ventricular function, and the length of ischemic time of the donor heart. Two patients have had permanent RBBB since the immediate postoperative period despite a normal donor electrocardiogram before harvesting. The temporal courses of QRS block varied widely in 9 patients. Thus, different mechanisms may have been active in various postoperative periods. The occurrence of QRS block was unrelated to morbidity and mortality in the recipients. Therefore, longer observation will likely establish the benign nature of the QRS block in this disease. PMID- 2266576 TI - Square root sign of left ventricular diastolic pressure curve in atrial septal defect. AB - The square root (dip and plateau) sign was observed in 7 of 21 adult patients with atrial septal defect (ASD). This study evaluated left ventricular (LV) diastolic filling dynamics and hemodynamic findings in 7 patients (Group 1) with, and 14 patients (Group 2) without the square root sign; 10 normal subjects (Group 3) served as controls. No significant differences were observed in LV end diastolic and end-systolic volumes, ejection fraction, or left to right shunt. In Group 1, 77% of LV filling was completed in the first half of diastole; this percentage was 49% and 53% in Groups 2 and 3, respectively (both p less than 0.01 versus Group 1). Early diastolic filling velocity (at 20% of diastole) in Group 1 was significantly greater, and late diastolic filling velocity (at 80% and 90% of diastole) was reduced in Group 1 compared to those in Groups 2 and 3 (all p less than 0.05). The average values for right and left ventricular end-diastolic pressures were significantly higher in Group 1 (11 +/- 2 and 10 +/- 4 mmHg, p less than 0.05) than Group 2 (7 +/- 2 and 7 +/- 2 mmHg, p less than 0.05). It is suggested that a constrictive pathophysiology due to 4 chambers interaction or right ventricular constraint may play a role in the genesis of the square root sign in ASD. PMID- 2266577 TI - Two cases of primary cardiac lymphoma presenting with pericardial effusion and cardiac tamponade. AB - The heart as the primary site of lesion in malignant lymphoma is extremely rare. We experienced 2 cases of malignant lymphoma whose initial presentation was massive pericardial effusion with cardiac tamponade. The first case was a 75-year old man who had shortness of breath for 1 week. Chest X-ray showed cardiomegaly (CTR 65%), and his condition was diagnosed as congestive heart failure at first and thereafter echocardiogram revealed pericardial effusion. The second case was a 76-year-old man who complained of exertional dyspnea which worsened over 2 weeks. His condition was diagnosed as congestive heart failure at first and echocardiogram revealed pericardial effusion. Pericardial drainage tapped bloody fluid and cytological examination revealed malignant lymphoma. After treatment, the first case lived for eleven months with no recurrence of pericardial effusion. The second case has lived for 4 years. We present these 2 cases can be defined as primary cardiac lymphoma according to McALLISTER and FENOGLIO, i.e., a lymphoma that involves only the heart and pericardium. More cases of primary cardiac lymphoma will be found in the future because of the ease with which the echocardiogram can detect pericardial effusion. PMID- 2266578 TI - Myocardial infarction induced by coronary venous thrombosis--an experimental study. AB - In a previous study, we proved experimentally that transmural infarction was produced in the area of the left anterior descending artery (LAD) by coronary sinus occlusion attributable to thrombus formation. In an attempt to produce infarction due to thrombus formation and to investigate the influence of thrombosis, the anterior interventricular vein (AIV) was occluded in this study. In each of 6 adult mongrel dogs, a balloon-tipped catheter was wedged in the AIV via the jugular vein. After the occlusion of blood flow by inflation of the balloon, thrombin (30-50 IU) was injected into the AIV to produce thrombi and the balloon was removed 60 min later. As a result, ischemic changes of ST and T in an ECG were clearly observed in all 6 dogs, and serum levels of myocardial enzymes supported the development of myocardial necrosis. Coronary arteriography performed 48 hours after the occlusion of the AIV showed normal findings in all 6 dogs, and residual thrombi in the AIV were observed in 5 dogs by coronary venography. In these 5 dogs, very local contraction band necrosis (CBN) was noted in the epicardium surrounding the AIV. These experimental findings indicate the following: 1) CBN can also be induced by coronary venous occlusion, 2) once the occlusive mechanism acts on the coronary venous system, the changes which are clinically similar to myocardial infarction can be induced regardless of its causes, 3) ischemic changes in myocardium can be localized in the epicardium irrespective of its causes. Therefore, these findings are considered to be important in the investigation of the clinical onset mechanism of myocardial infarction. PMID- 2266579 TI - Molecular cloning and chromosomal localization of a gene coding for human cardiac myosin heavy-chain. AB - alpha- and beta-human cardiac myosin heavy-chain (MHC) genes, which correspond to MYH6 and MYH7, respectively, according to Human Gene Mapping nomenclature, were isolated from human genomic and cDNA clones, using two rat cardiac pCMHC26: alpha MHC type; and pCMHC5: beta-MHC type as probes, and characterized. The alpha-MHC type cardiac genomic DNA clone and the beta-MHC type cardiac cDNA clone were used as probes in the Southern analysis of human genomic DNA from human-Chinese hamster or human-mouse somatic cell hybrids. The results showed that the human cardiac MHC gene is assigned to chromosome 14 and the human cardiac and skeletal MHC genes do not cosegregate as do the mouse cardiac and skeletal MHC genes. For further analysis, a regional mapping method was used. DNA from 4 human deletion and 3 human duplication cell line were prepared for southern blotting, hybridized with human cardiac alpha- and beta-MHC DNA probes, and the hybridization intensity relative to 46, XX or 46, XY DNA was estimated. The results showed that two human cardiac MHC genes segregated with the 14cenq13 region of the long arm of human chromosome 14. In situ hybridization of 3H-labeled human cardiac alpha MHC probe to normal human metaphase chromosome independently confirmed this result. PMID- 2266580 TI - Mitochondrial cytopathy. PMID- 2266581 TI - [Asymptomatic infection of Legionella pneumophila in four cases with pulmonary diseases]. AB - In view of the wide-spread existence of legionellae in cooling-tower and other environmental water, asymptomatic infection of this organism could occur. In order to verify the possibility of colonization of legionellae at lower respiratory tract of patients with various pulmonary diseases, a total of 22,036 sputum samples from in- and out-patients at National Sanyoso Hospital were examined during a five-year period from September, 1984 to August, 1989. Four (0.073%) out of 5,502 cases were culture-positive for L. pneumophila. L. pneumophila strains were isolated from expectorated, subsequently washed sputum samples of two male and two female patients with respiratory tract diseases. The identification of the isolates was genetically confirmed by the fluorometric microplate DNA-DNA hybridization method. The serogroup (SG) and viable counts of L. pneumophila per ml of sputum of each patient were as follows: 73 y/o female K.H., SG-6, 10(3) CFU; 75 y/o male H.J., SG-5, 10(4) CFU; 61 y/o female M.S., SG 5, 10(5) CFU; and 77 y/o male M.G., not-agglutinable against SG-1-6 antisera, 10(4) CFU. None of the four patients was clinically suspected of legionellosis and antibody titer of paired sera remained 1:64 or lower than 1:32. From these findings, we concluded that L. pneumophila can cause, though quite rarely, asymptomatic infection in human respiratory tract. None of the environmental samples obtained from in- and out-side of the Hospital was culture-positive for legionellae. Thus, the source of infection has remained unknown. PMID- 2266582 TI - [Induction by Staphylococcus aureus L-form of tumor necrosis factor-alpha from macrophages]. AB - Induction of tumor necrosis factor-alpha (TNF-alpha) by Staphylococcus aureus L form was investigated. The supernatant of a macrophage culture mixed with S. aureus L-form showed a potent cytotoxic activity to L cells. Addition of anti TNF alpha antibody inhibited completely the cytotoxic activity of the supernatant, indicating that the activity might be due mostly to TNF-alpha. To investigate localization of TNF-alpha production, the membranes of hypotonicity treated L form were layered on a step-gradient composed of an upper and lower layers of 35% and 50% sucrose, respectively. The membranes were banded at the interface of 35% and 50% of sucrose. The activity of TNF-alpha production of the membrane fraction was 10-times higher than that of the soluble fraction. PMID- 2266583 TI - [Quantitative microdilution plate hybridization to determine genetic relatedness among bacterial strains]. PMID- 2266584 TI - [Multiple primary malignancies in patients with head and neck cancer]. AB - From July, 1978 to December, 1985, 1,138 cases of malignancies of the head and neck were treated at the authors' hospital, and up to June, 1986, 132 patients with multiple primary malignancies were detected. In all cases, the incidence rate of a multiple primary malignancy was 11.6%. In 45 (33.0%) of these head and neck cancer cases, the multiple cancer was detected simultaneously, and as for the other cases (66.7%), they were discovered metachronously. In patients with a cancer of the mesopharynx, the incidence rate of a multiple primary malignancy was the highest (25.8%), whereas in those with a cancer of the parotid gland and in those with a cancer of the hypopharynx, the incidence rates were 20.0% and 14.9%, respectively. In most patients the second malignancy occurred in the same head and neck region, and in the rest, the second malignancy was a gastric cancer, a lung cancer, or an esophageal cancer in that descending order. Of the 45 synchronous cancer cases, ten were a thyroid cancer, most being latent. In head and neck malignancies, the authors stress the importance of a precise investigation prior to start of therapy and of maintaining follow-up investigations after therapy. PMID- 2266585 TI - [The marrow granulocyte reserve in lung cancer patients]. AB - The marrow granulocyte reserve (MGR) of patients with lung cancer have been estimated by measuring the maximum neutrophil increment after administration of hydrocortisone. The MGR was found to have decreased in four of 19 untreated patients, but the reason for this decrement was not clear. Further, there were no differences in the MGR between the cell types or cancer stages. The MGR in patients 70 years old or older tended to be decreased. After chemotherapy or radiation therapy, the MGR depressed significantly. However, on administration of OK 432, the MGR significantly increased in two patients who had received radiation therapy and whose MGR had been deficient initially. PMID- 2266586 TI - [Relationship between the prognosis and nuclear DNA histograms in gastric cancer patients with a synchronous liver metastases who were given a combined gastrectomy and hepatectomy]. AB - Out of 127 gastric cancer cases with a synchronous liver metastases, the relationship between the prognosis and the nuclear DNA contents in the primary and liver metastatic foci has been investigated in 10 relatively noncurative patients who had received a combined gastrectomy and hepatectomy. In 3 out of 5 long-term survival cases, low ploidy patterns were seen in both foci, whereas in 1 out of 5 short-term survival cases, a multiplicity was observed, i.e., a low ploidy in the primary focus and a high ploidy in the liver. In the other 4 short term survival cases, high ploidy patterns were noted in both foci. PMID- 2266587 TI - [The efficacy of bone scintigraphy screening in postoperative follow-up of breast cancer patients]. AB - Discussed are 110 breast cancer patients given surgery, totaling 70 stage 1 cases, 22 stage II cases, 15 stage III cases, and 3 stage IV cases, that were routinely followed-up postoperatively at 6 or 12-month intervals, said follow-ups including bone scintigraphy screening. Among 394 bone scintigrams taken of these 100 patients, 15 new cases of a bone metastasis were detected, 9 of which had either a local recurrence or an associated metastasis at the time that their bone metastasis was detected. In only 1 case, at more than five years after surgery, was a bone metastasis detected by bone scintigraphy, and even this case had another metastasis at that time. Therefore, the value of bone scintigraphy screening as part of the follow-up of postoperative breast cancer patients is questioned. PMID- 2266588 TI - [Problems associated with radical neck dissection in patients with tongue carcinoma: four cases of stage I tongue carcinoma that recurred in the cervical area after the dissection]. AB - Reported are four cases of a stage I tongue carcinoma which recurred in the cervical area after a radical neck dissection (RND). In all cases, the primary lesion was controlled with radium needle implants. Clinically, these tumors manifested endophytic growth and, histologically, had a high malignant grading. In most cases, a latent lymph metastasis appeared within 6 months after initial treatment and an early metastatic lesion developed beyond the capsule of the node. The site of cervical recurrences was located in non treated areas that were outside the range of the RND. PMID- 2266589 TI - [A giant struma histologically confirmed as a medullary carcinoma with multiple systemic bone metastasis]. AB - Reported is the case of a 46 year old woman with no significant family medical history, who presented a neck tumor that she had had for about ten years. This large tumor was noted on her admittance to hospital due to a bone fracture. She subsequently underwent a resection of this giant neck tumor. A histologic examination of the specimen revealed a medullary carcinoma of the follicular variety. Silver impregnation by the Grimelius method caused a positive reaction, and an electron-microscopic examination revealed round, electron-dense, endocrine granules about 195 nm in diameter, Immunohistochemically, the carcinoembryonic antigen (CEA) and the presence of calcitonin proved the cells to be cancerous. PMID- 2266590 TI - [A well differentiated fibrosarcoma arising in left neck region]. AB - The frequency of a fibrosarcoma, based on current criteria, is less than 10% of soft tissue sarcomas. It is most common in the region of extremities and the trunk and relatively rare in the head and neck region. Therefore, of interest is a case of a well differentiated fibrosarcoma arising in left neck region of a 69 year-old woman that is reported. The excised tumor consisted of a firm, partially lobulated mass with a fibrous capsule that measured 8 cm at its greatest diameter. Histologically, the tumor tissue was rather uniform and often had a fasciculated growth pattern consisting of spindle shaped cells and interwoven collagenous fiber in a parallel fashion. To achieve a diagnosis, it was necessary to differentiate this type of fibrosarcoma from aggressive fibromatosis and myogenic tumor (leiomyoma or leiomyosarcoma). PMID- 2266591 TI - [A case of multiple peripheral pulmonary carcinoids showing a diffuse lung disease synchronously associated with sigmoid colon cancer]. AB - Reported is a rare case of a multiple peripheral pulmonary carcinoids showing a diffuse lung disease synchronously associated with a sigmoid colon cancer. An abnormal chest shadow was detected in a 75-year-old male by X ray during a periodic health examination. After admission to hospital for a more thorough examination he was found to have a sigmoid colon cancer. A CT scan of his chest suggested sarcoidosis, but the results of a bronchofiberscopic examination appeared normal. Subsequently, a TBLB specimen revealed typical carcinoid tumors. Thus, the diagnosis of diffuse multiple peripheral carcinoids was made. A surgical resection of the sigmoid colon cancer was performed successfully, but five months later, the patient died of acute pneumonia. An autopsy was not permitted. Also discussed are multiple pulmonary carcinoids and a double cancer. PMID- 2266592 TI - [A case of synchronous multiple primary cancers of the stomach and kidney]. AB - In line with an increase in the incidence of multiple primary cancers, we have encountered a case of synchronous multiple primary cancers of the stomach and the left kidney. The patient, a 69-year-old male, visited our hospital after experiencing epigastric discomfort for three months. An advanced gastric cancer, Borrmann III type, was detected by endoscopic examination. Preoperative abdominal computed tomography also revealed a large low density mass occupying the upper part of the left kidney. On angiography, the left kidney showed a hypervascular mass, showing pooling and tumoral stains, thereby suggesting a renal cell carcinoma. The patient thus underwent a subtotal gastrectomy with an R2 lymph node dissection and a left radical nephrectomy. Histologically, the gastric lesion was a poorly-differentiated adenocarcinoma and the left renal lesion was a renal cell carcinoma of the clear cell type. PMID- 2266593 TI - [A neuron-specific enolase (NSE) positive leiomyosarcoma]. AB - A 40-year-old woman with multiple skin tumors was admitted to our hospital on September 5, 1989. Extensive studies by means of light and electron-microscopic examination and immunohistochemical analysis revealed a neuron-specific enolase (NSE) positive leiomyosarcoma. The level of her elevated serum NSE decreased after receiving her initial chemotherapy, but after the fourth session of chemotherapy, the NSE began to elevate again and she died on December 25, 1989. NSE appears to be a useful marker for determining if the neuronal and neuroendocrine cells are normal. This rare case, however, seems to demonstrate that abnormal, nonneuronal cells like a sarcoma also open metabolic pathways to synthesize NSE. PMID- 2266594 TI - [Phospholipase A2 activating factor in sera of patients with psoriasis vulgaris]. AB - Phospholipase A2 (PL-A2) has been known to be activated in either affected or un affected skin of patients with psoriasis vulgaris. The present study was designated to investigate whether or not there is a factor activating PL-A2 in their sera, using cultured murine epidermal cells (NCTC-2544). The cultured cells prelabeled with 3H-arachidonic acid (3H-AA). After adding a serum, the release of 3H-AA into medium from the cells was measured. The sera from 20 patients with psoriasis vulgaris showed significantly increased releases of 3H-AA as compared with those by sera from 10 healthy individuals, indicating that there may be a PL A2 activating factor in the sera of psoriasis vulgaris. The PL-A2 activating factor in the patient sera was not inactivated with added 2 different PL-A2 inhibitors. The sera were not able to produce 3H-AA from 3H-AA labeled phospholipids. Therefore, PL-A2 activating factor does not seem to be PL-A2 itself existing in the sera. Through heat stability, dialysis, and fractionation studies, the PL-A2 activating factor in sera was found to be a protein, which had a molecular weight of more than 50 kd and was stable at 56 degrees C. PMID- 2266595 TI - [Serum apolipoprotein levels in psoriatic patients]. AB - Serum apolipoprotein and lipid levels were determined in 33 psoriatic patients, 26 males and 7 females, and in 61 normolipemic, non-psoriatic controls matched for age and sex. The psoriatic patients had significantly higher levels of triglyceride and lower levels of apo B. The male psoriatic patients showed a tendency to have lower levels of LDL-cholesterol. The levels of cholesterol, HDL cholesterol, apo A-I, apo A-II, apo C-II, apo C-III and apo E did not differ significantly from those of the controls. The relevance of these findings to the development of psoriasis remains to be established. PMID- 2266597 TI - [Generalized pustular psoriasis in siblings]. AB - Generalized pustular psoriasis in siblings, 31-year-old male and 26-year-old female, is presented. In both cases, pustular lesions appeared in childhood and typical eruption of psoriasis vulgaris was not observed during their clinical course. Cholecystitis and chronic tonsillitis of the brother and periodontitis and chronic tonsillitis of the sister were considered to be possible provocative factors. HLA-A24, Bw52-, DR2, as the common HLA haplotype in our cases, was estimated. PMID- 2266596 TI - [A case of Stewart-Treves syndrome--treatment with recombinant interleukin 2 and a review of Japanese literature]. AB - A 76-year-old woman developed angiosarcoma 11 years after a radical mastectomy in the chronic lymphedema of the ipsilateral arm, referred to as Stewart-Treves syndrome. The patient was treated by intravenous and intralesional injection of recombinant interleukin 2 (rIL-2; TGP-3, Takeda Chemical Industries, LTD, Osaka). Intralesional injection was more effective than systemic administration. After a month, the lesion where the local injection was done showed little tumor cells with a dense infiltrate composed of lymphoid cells. It was observed that NK activity, LAK activity and IL-2 receptor positive T-cells in the peripheral blood increased during the administration of rIL-2. As the lesion was too large to be treated with rIL-2 alone, radiotherapy was performed. But the patient had no remarkably improvement and died 16 months later from the onset. Immunotherapy with rIL-2 can be useful for angiosarcoma and more effective regimen of rIL-2 is a important problem. PMID- 2266598 TI - [Familial cases of cutaneous myxomas and spotty pigmentation (Carney's complex)]. AB - In 1985, Carney et al reported a complex of myxomas, spotty pigmentation, and endocrine overactivity and subsequently demonstrated dominant inheritance of the condition. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: (1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoma, (4) spotty mucocutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease (Cushing's syndrome), (6) testicular tumors (sexual precocity), (7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). We encountered a family with an affected mother and daughter. Case 1 was a 43-year-old woman with multiple cutaneous myxomas, mammary myxomas and spotty mucocutaneous pigmentation. Case 2, the 19-year-old daughter of case 1 had multiple cutaneous myxomas and spotty cutaneous pigmentation. These two cases both met the criteria for the diagnosis of the complex. Our report is believed to be the first report on the complex in Japan. PMID- 2266599 TI - [Skin high-molecular-weight protease. 2. Biochemical properties]. AB - The purification of High-Molecular-Weight Protease from Wistar Rat's skin was previously investigated and reported. Some properties of this enzyme were subsequently investigated. This enzyme showed high activities toward succynyl leucyl-leucyl-valyl-tyrosine-methylcoumarinamide (SLLVT-MCA). The addition of 0.03% sodium dodecyl sulphate (SDS) stimulated enzyme activity to 2,000% of the initial activity. The pH optimum was pH 8.5 in the presence of 0.03% SDS, but pH 6.0-8.5 in the absence of SDS. This enzyme was inhibited by one of serine protease inhibitors, diisopropylfluorophosphate (DFP) strongly. It was also inhibited by some of SH protease inhibitors, N-ethylmaleimide (NEM), iodoacetamide (IA), and leupeptin. Interestingly, chymostatin, a serine and SH protease inhibitor also inhibited enzyme activity. These results show that both serine and cysteine++ residues are related to the enzyme activity of High Molecular-Weight Protease. PMID- 2266600 TI - Application of synthetic DNA probes of human alpha satellite consensus monomer for detection of centromere-involved chromosome abnormalities. AB - We have synthesized the alphoid monomer of 171 bp based on the consensus sequence of human alpha satellite DNA and constructed a clone of dimeric or tetrameric sequence unit. Southern blot analysis using the clone as a probe showed restriction site periodicities in human DNA digested by EcoRI or BamHI. The synthetic consensus unit could detect the alpha repeated centromeric regions of all human chromosomes by fluorescence in situ hybridization. Using the cells having a dicentric X chromosome, we showed that the two centromeric regions were stained with fluorescent alpha satellite DNA probes. Thus the probe would be useful to detect chromosomal abnormalities such as dicentrics. PMID- 2266601 TI - Investigation of paternity establishing without the putative father using hypervariable DNA probes. AB - Seven kinds of DNA probes which recognize hypervariable loci were applied for paternity test. The putative father was decreased and unavailable for the test. The two legitimate children and their mother (the deceased's wife) and the four illegitimate children and their mother (the deceased's kept mistress) were available for analysis. Paternity index of four illegitimate child was investigated. Allelic frequencies and their confidence intervals among unrelated Japanese individuals were previously reported from our laboratory, and co dominant segregation of the polymorphism was confirmed in family studies. Cumulative paternity indices of four illegitimate children from 16 kinds of standard blood group markers were 165, 42, 0.09, and 36, respectively. On the other hand, cumulative paternity indices from 7 kinds of DNA probes are 2,363, 4,685, 57,678, and 54,994, respectively, which are 14, 113, 640, 864, and 1,509 times higher than that from standard blood group markers. The DNA analyses gave nearly conclusive evidence that the putative father was the biological father of the children. Especially, the paternity relation of the third illegitimate child could not be established without the DNA analyses. Accordingly, DNA polymorphism is considered to be informative enough for paternity test. PMID- 2266602 TI - A Japanese male infant with the Weaver syndrome. AB - A 15-month-old male infant who had pre- and postnatal overgrowth, accelerated bone maturation and characteristic facial appearance was described. Although a Japanese female with Weaver syndrome previously reported had slightly different clinical manifestations from others, our patient had typical clinical features of Weaver syndrome. We suggest that a genetic mutation of the syndrome may be the same in Japanese as other ethnic groups and that Weaver syndrome may be an autosomal dominant disorder with variable expressions. PMID- 2266603 TI - A disease with immune deficiency, skin abscesses, pancytopenia, abnormal bone marrow karyotype, and increased sister chromatid exchanges: an autosomal recessive chromosome instability syndrome? AB - A 19-year-old girl is described with microcephaly, short stature, mental retardation, pigmentation of the skin, and recurrent skin abscesses over the whole body. Her elder brother and sister both showed growth and developmental retardation, microcephaly, and anemia. Both died during childhood. Their parents were first cousins. Laboratory studies of the proband revealed hyperchromic erythrocytes with an increased HbF content, thrombocytopenia, an impaired mitogenic response of the PHA-stimulated lymphocytes, and partial impairment of humoral and cellular immunity. She developed pancytopenia in the terminal stage of the disease. Cytogenetic studies of the bone marrow revealed 46,XX, 15p+, -18, +mar karyotype, increased chromosomal aberrations and sister chromatid exchanges, in cultured lymphocytes and skin fibroblasts. She died at age 20. Thus, the disorder in the patient was deduced as an unclassified chromosomal breakage syndrome with an apparently autosomal recessive inheritance. PMID- 2266604 TI - Analysis of human vaginal secretions using rabbit anti-human vaginal secretions: detection of non-serum proteins. AB - The antigens detectable in human vaginal secretions (HVS) have been analyzed by using a rabbit anti-HVS serum. After absorption by a pool of human sera, this antiserum on immunoelectrophoretic analysis produced three precipitation lines between the HVS and the antiserum. These lines were found at gamma (a line), beta gamma (b line) and beta (c line) globulin regions. Their respective incidences of appearance among 59 HVS specimens obtained from 50 women were 46 (78%), 56 (95%) and 29 (49%). Of these HVS specimens, 57 (97%) were positive for one or more of these antigens. These three antigens, a, b, and c can be considered useful markers to determine the presence of the HVS. The origin of the HVS proteins and the influence of the non-serum proteins from the upper genital tracts are also discussed. PMID- 2266605 TI - [A histopathological study on the cardiac conduction system in sudden death of unknown origin]. AB - For the purpose of searching for the underlying mechanism of sudden death, 46 cases of non-traumatic sudden death were selected from autopsied cases during the past 8 years from 1980 to 1987 in the department of legal medicine, St. Marianna university school of medicine. These included 40 males and 6 females ranging from 30 to 60 years of age. Autopsy revealed the existence of cardiac abnormalities in 41 cases (89.1%). Among them, acute myocardial infarction was found in 23 cases (56.1%) and there were 16 cases (39.0%) diagnosed as acute cardiac failure because of the absence of organic abnormality in the heart. Out of the latter cases having undefined etiology of sudden death, 10 cases were selected and histopathological study on the cardiac conduction system was performed by Lev's method. Fatty infiltration in the sinus node, in the atrio-ventricular node and bundle of His was observed in 5 cases, severe stenosis of atrio-ventricular nodal artery in 2 cases and subendocardial hemorrhage of left bundle branch in 1 case. In the remaining case, no pathological abnormality was observed. These results suggest that the organic lesion of the cardiac conduction system could underlies the clinically undefined cause of sudden death. PMID- 2266606 TI - [A simplified method for evaluation of brain function--basic and clinical study on electroencephalogram by the nasopharyngeal lead]. AB - In making a decision for death, it is well said that brain stem electroencephalogram (EEG) could be an important index. We applied Ishida's nasopharyngeal lead to animals (canine), normal healthy men and patients with brain dysfunction. In normal healthy men, the nasopharyngeal lead revealed clear brain waves. Additionally, we tried a photic stimulation in all the models and a gradual removal of the cerebrum in canines to investigate whether interaction between Ishida's nasopharyngeal lead and the cortical electroencephalogram exists. Furthermore, whenever there was a chance, we examined instances with brain dysfunction by the method, and confirmed that brain waves obtained from Ishida's nasopharyngeal lead were derived from the skull base. PMID- 2266607 TI - [Sex identification by analysis of DNA extracted from hard tissues]. AB - Sex identification of unidentified two bleached skeletons by the method of DNA analysis in addition to the morphological examination was performed. Bones and teeth were taken out for the DNA analysis, and cracked to compounds by liquid nitrogen. DNA was extracted by the standard procedure. We used two methods for sex identification by DNA analysis; one is Southern blot hybridization with Y chromosome specific probe (PHY10; 3.4kb), and the other is PCR (polymerase chain reaction) amplifying with sex chromosome specific fragments (alphoid satellite family). These two methods enable us to identify the sex of the two cases presented here more correctly with sufficient evidence than depending only on morphological examination. With some technical difficulties, it is possible to put DNA analysis including Southern blot hybridization or PCR into practical determination of sexing of hard tissues such as a piece of bone or a tooth, and old samples. Therefore, they seem to be effective methods applicable to forensic science. PMID- 2266608 TI - [Scanning electron microscopic study of rat lungs in experimental chronic paraquat poisoning]. AB - It is well known that Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride), used widely as a herbicide, causes a primary toxic effect in the lungs of humans and laboratory animals. This paper describes the pulmonary changes of chronic paraquat poisoning in rats, comparing scanning electron microscopic findings. Twenty-four rats were given repeated injections of 10/kg body weight paraquat intraperitoneally for 6 consecutive months, and six control rats were given 0.9% NaCl solution. The animals exposed to paraquat showed thickening of alveolar septum, inflammatory cell infiltration, interstitial fibrosis, and marked proliferation of alveolar macrophages. Among them four rats (21%) showed the typical findings of diffuse pulmonary fibrosis. Lesions were more severe at the subpleural region of the lung. The desquamation of alveolar epithelial cells and subsequent exposure of the basement membranes were observed in places. Although alveolar epithelial cells both in the type I and the type II were prolific, the type II cells showed partial loss of microvilli and projections. These findings may indicate the lowering of the type II cell function and subsequent decrease of surfactant excretion which causes respiratory insufficiency. Furthermore, alveolar macrophages showed a tendency to increase in number with progressive development of fibrosis. This tendency may support the hypothesis by Schoenberger et al., in which alveolar macrophages release both fibronectin and a growth factor for fibroblast after paraquat exposure. PMID- 2266609 TI - [Driver identification of the motorcycle in motorcycle/car accidents]. AB - A series of motorcycle/car collision experiments and in-depth investigations involving motorcycle/car accidents with two riders were carried out in order to study the difference in behavior and injuries between the driver and the passenger of the motorcycle during a collision, and to provide general data for identifying their seat positions on the motorcycle in traffic accidents. In all the tests, two Hybrid II dummies were seated on the double seats of the motorcycle as riders. The motorcycle collided against the front door, front end or rear door of the passenger car at a speed of 50 km/h, at impact angles of 60 degrees, 90 degrees or 120 degrees. The speeds of the passenger car were tested at 0 km/h or 25 km/h. With different speeds of vehicles and different impact angles, the difference in rider behavior between the driver and the passenger was distinctly verified by analysis of high speed films. It is possible to distinguish the driver's injuries from the passenger's. The abrasion and/or contusions in the chest, face and groin area were severe for the drivers, but less serious for the passengers. The typical injuries of the driver can be expected in terms of the rider behavior during collision from 25 ms to about 150 ms after starting contact. The data and information can be used to clarify the question of who was driving in accident reconstruction. PMID- 2266610 TI - [An experimental study on driver identification of passenger car in vehicle to vehicle accidents]. AB - A series of full-scale vehicle-to-vehicle oblique collision experiments was carried out for providing general data to clarify the question of seating positions. In all test, two unrestrained anthropometric dummies (Hybrid II) were seated on front seats in passenger cars as occupants. The bullet car collided against the target car running with 25 km/h, at 50 km/h, at impact angles of 120 degrees and 150 degrees. Five impact configurations between occupant regions and interior of vehicle were evaluated: head-face/windshield, head-face/A-pillar, chest-abdomen/instrument panel, upper body/inside door and lower extremities/instruments panel. Comparative occupant injuries and vehicle response data were obtained from electronic instrumentation, high-speed movie films and visual observations. No characteristic driver injuries was observed in oblique collision experiments. The crush characteristics of the vehicle interiors and occupant behavior had significant effect in determining the actual injury once contact occurred. The differences of injuries in occupants occurred depend on impact configurations of vehicles. Therefore, on the driver identification, it is important to clarify kinematics of occupants during the impact by an analytical reconstruction. The data and information can be used to determine who was driving in actual traffic accidents for the forensic medicine expert. PMID- 2266611 TI - Estimating age through the amino acid racemization of acid-soluble dentinal peptides. AB - We studied the possibility of estimating age through the amino acid racemization of acid-soluble dentinal peptide (SP). The correlation of the D/L ratio of aspartic acid and the actual age was the highest in the SP extracted with 1 M HCl (r = 0.996, sigma = +/- 0.8), followed by the total amino acids (TAA:r = 0.995, sigma = +/- 1.0), and the SP extracted with 2 M HCl (r = 0.980, sigma = +/- 1.9) and then SP extracted with 5 M HCl (r = 0.951, sigma = +/- 2.7). The rate of the racemization reaction decreased in the order of SP extracted with 1 M HCl, 2 M HCl, 5 M HCl and the total amino acids (TAA). Consequently, an extraction with 1 M HCl seemed best for estimating the age from SP to serve actual cases. PMID- 2266612 TI - Racemization velocity of aspartic acid in dentine. AB - To investigate the racemization of dentinal amino acids furthermore, and thereby to estimate age more accurately, fundamental heating experiments dealing with aspartic acid in dentine were carried out. The racemization velocity was determined and compared not only for the total amino acids (TAA), but for insoluble collagen (IC) as well as soluble peptide (SP) fractions. In TAA and IC, with the passage of time, their racemization deviated from the mode of the primary reaction, whereas in the SP, an extremely stable increase in D/L ratio was maintained for a longer time, fulfilling the mode of the primary reaction. When samples are left drying, the racemization velocity was greatest in the IC but considerably less in the SP, indicating results opposite to those found in the living state. PMID- 2266613 TI - [Homicidal poisoning by aconite: report of a case from the viewpoint of clinical forensic medicine]. AB - A case of homicidal poisoning by aconite is reported from the viewpoint of clinical forensic medicine and analytical chemistry. Jesaconitine was detected in the vomitus, stomach contents, plasma and urine at concentrations of 32.2, 5.48, 0.433 and 1.07 micrograms/ml, respectively. The total amount of jesaconitine in the stomach contents was 1.3 mg. Macroscopic autopsy revealed hemorrhagic pulmonary edema, and histologically, diffuse contraction-band necrosis was evident in the myocardium. Exogenous administration of adrenaline or endogenous release of catecholamines are known to induce hemorrhagic pulmonary edema and contraction-band necrosis, and aconitine is reported to cause release of endogenous catecholamines centrally and to induce neurogenic pulmonary edema and ventricular-type arrhythmia. Therefore, the chief cause of death in this case was considered to be aconite-induced centrogenic arrhythmia. PMID- 2266614 TI - [An autopsy case of atypical hanging: were arteries and air passage obstructed?]. AB - A housewife hanged herself with her left foot on a washstand and her right foot above the floor. The ligature mark encircled once horizontally at the height of the laryngeal prominence (horizontal part), crossed at the front of the neck, rose to the posterior regions of the mandibular angles and extended upward to the preauricular regions (ascending part). Petechial haemorrhage was in the conjunctivae and froth was in the air passage. Vertebral arteries are not obstructed by the compression of the horizontal part (Brinkmann et al., 1981). Vertebral arteries are possibly not obstructed by the traction of the ascending part (experiment on our own necks). An air passage is not obstructed by the compression of the horizontal part (Langreuter, 1886; Strassmann, 1922). Obstruction of an air passage by typical hanging is removed by putting the bent head to upright position (Langreuter, 1886). From these experimental observations we clarified that in our case the vertebral arteries and air passage had very possibly not been obstructed by the hanging while 70-80% of her body weight, i.e. 40-45 kg, had loaded on the neck. The force to obstruct the arteries and air passage by hanging, which has been quoted in texts and articles in Japan, is absolutely due to the value for "typical" hanging. PMID- 2266615 TI - [An autopsy case of sudden death due to hyperthyroidism]. AB - A rare autopsy case of death due to thyroid crisis is reported. A 45-year-old lean woman with pigmentation of the skin was found dead at the seaside. The autopsy findings were as follows: The enlarged thyroid gland (35.5 g) had a histological finding of diffuse hyperplastic goiter (hyperthyroidism). The thymus (28.5 g) was enlarged and parenchymatous. The lymphocytes in the thymus and spleen were conspicuously proliferated, probably due to secondary adrenal cortex insufficiency. The adrenal cortex was slightly atrophic. Hemosiderin-laden macrophages in the lung, and centrilobular necrosis, microscopic bleeding, fibrosis, and nodular regenerative hyperplasia of the liver indicated the persisted heart failure. A small pericardial scar was found at the right ventricle of the heart (280 g), and the histological finding of the heart was only congestion. Acetone was detected in a relatively high concentration in the blood (72 micrograms/ml), urine (139 micrograms/ml), bile (32 micrograms/ml) and gastric contents (38 micrograms/g), probably due to metabolic disorder from thyroid crisis. In conclusion, the cause of death was diagnosed as sudden death due to thyroid crisis from hyperthyroidism. PMID- 2266617 TI - [Grounded theory approach. Applying grounded theory method to nursing research]. PMID- 2266616 TI - [Grounded theory approach. Understanding the grounded theory approach]. PMID- 2266618 TI - [Grounded theory approach. Trends in grounded theory in nursing research]. PMID- 2266619 TI - [Grounded theory approach. An analysis of the incomprehensibility of difficult patients for nurses]. PMID- 2266620 TI - [Grounded theory approach. How to apply the grounded theory approach to nursing research]. PMID- 2266621 TI - [A study of guidance to clinical practice]. PMID- 2266622 TI - [The approach to the English monograph. To challenge your translation, to discover your mistakes (6)]. PMID- 2266623 TI - [Spontaneous production of interleukin-1 alpha and beta by alveolar cells from patients with sarcoidosis]. AB - The spontaneous production of interleukin-1 alpha and beta by alveolar cells obtained by BAL from 7 active pulmonary sarcoidosis and 5 normal volunteers was evaluated. The activity of disease in one case was considered to be highly active because of the chest X-ray pattern (diffuse micronodular shadows), highly intense Ga up take in lungs, increased number of BAL cells and high level of S-ACE. The contents of IL-1 alpha and beta were measured by ELISA in the culture supernatants of alveolar cells after 24 hours culture without any stimulus. Large amounts of IL-1 alpha and beta production were found in highly active case. No significant amount of IL-1 alpha and beta, however, was detected in 6 other active sarcoidosis cases and 5 normal volunteers. Therefore, spontaneous release of IL-1 alpha and beta in vitro from alveolar cells in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment and its relationship to the spontaneous remission of sarcoidosis in Japanese patients was discussed. PMID- 2266624 TI - [Bronchiolitis obliterans organizing pneumonia (BOOP) in Japan]. AB - Twenty-nine patients with bronchiolitis obliterans organizing pneumonia (BOOP) in Japan diagnosed by an open lung biopsy were reviewed. A total of 70% of the patients were idiopathic and 2/3 of the remaining were associated with connective tissue disease. All 29 cases of BOOP showed bilateral pulmonary infiltration on chest X-rays. BOOP can be classified based on the chest X-ray findings into three major types, Type I, Type II and unclasSified type. In Type I shadows appear in the lung fields. In Type II abnormal shadows are seen in the bi-basilar peripheral field with the reduction of the lung volume. Cases of Type I showed inflammatory findings more frequently than cases of Type II. Among 29 BOOP patients, two idiopathic cases died. PMID- 2266625 TI - [Clinical study on asbestos pleurisy and review of literature]. AB - Seven asbestos workers with asbestos pleurisy were investigated in terms of clinical symptoms, findings of pleural biopsies and course of chest roentgenograms. All cases were male and smokers. Duration of asbestos exposure ranged from 3 to 33 years (mean: 20.6 years). Duration between initial exposure and onset of the pleurisy ranged from 22 to 34 years (mean: 28.7 years). Five pleural effusions were aseptic and exudative, and one had sanguineus and eosinophilic effusion. According to the findings of pleural biopsies, our cases were classified into 2 groups. Group A (4 cases) had "basket-weaving formation" on the parietal side and inflammatory changes on the visceral side. No circulating autoantibodies were found in group A. Group B (3 cases) had no "basket-weaving formation" but only intensive inflammatory changes. These 3 cases were respectively complicated with anti-GBM antibody mediated glomerulonephritis, with acute interstitial pneumonia, and with rheumatoid arthritis and acute interstitial pneumonia. They all had circulating autoantibodies. In the course of chest roentgenograms, 6 of the 7 cases finally showed diffuse pleural thickenings which involved obliterations of costo-phrenic angles. Among them, one case developed into progressive pleural fibrosis. It was concluded that asbestos pleurisy can be classified into 2 groups according to the mechanism of occurrence, and immunological changes should be recognized as one of the mechanisms of asbestos pleurisy. PMID- 2266626 TI - [Lung function measurement of small airway obstruction in idiopathic interstitial pneumonia]. AB - Small airway obstruction in idiopathic interstitial pneumonia was studied in 54 cases of interstitial pneumonia accompanied by restrictive, but not obstructive impairment (%VC less than 80%, FEV1/FVC% greater than 70%). Correlation analysis of %VC showed that small airway obstruction seemed to play a role in the decrease in VC in these cases. Cases were then divided into two groups. In group A, restrictive impairment was caused by the decrease in TLC (%TLC less than 80% & %RV less than 120%) and in group B, it was caused by increase in RV (%TLC greater than 80% & %RV greater than 120). Cases of idiopathic interstitial pneumonia (IIP) were preferentially categorized into group A. Statistical comparison of the lung function measurements revealed that lung parenchyma was altered less severely whereas small airway obstruction was more advanced in group B than group A. Group B was divided into two subgroups, the subgroups of IIP cases and of the other disease cases, and the latter had a larger lung volume and more severely impaired small airway function. Furthermore, IIP cases from group A had less severely altered lung parenchyma than IIP cases from group B. Smoking habits did not seem to be related to these results. The results indicate that in most cases of interstitial pneumonia other than IIP, the lung function was characterized by small airway obstruction rather than decreased lung volume, and some cases of IIP also showed a similar trend. In addition, a long-term study of lung function was made in some cases of interstitial pneumonia and it was shown that small airway obstruction could change in severity after a time interval. PMID- 2266627 TI - [A prospective study of idiopathic interstitial pneumonia and collagen vascular disease preceded by interstitial pneumonia]. AB - The incidence and latency period of collagen vascular disease (CVD) were surveyed prospectively in patients originally diagnosed as idiopathic interstitial pneumonia (IIP). We also examined whether there were differences between IIP and CVD preceded by interstitial pneumonia. Background information, extrapulmonary symptoms, smoking history, laboratory findings, prognosis (Kaplan-Meier estimates), respiratory functions, and radiological findings were compared. The subjects consisted of 68 patients of whom 13 (19%) developed CVD (RA; 5 cases, DMPM; 5 cases, SLE; 1 case, Sjoegren syndrome; 1 case, Overlap syndrome; 1 case). The latency period for development of CVD was 24.9 +/- 39.2 (mean +/- SD) months. IIP patients who developed CVD were predominantly female and were younger than those without CVD (p less than 0.05). These patients also had faster ESR, higher CPK values, and a higher incidence of arthralgia, joint deformity and clubbed fingers (p less than 0.05). Abnormal shadows around costo-phrenic angles were seen more frequently in patients with CVD (p less than 0.05). These results suggest that quite a number of patients with IIP develop CVD. The clinical course of these patients should be followed by keeping these clinical findings in mind. PMID- 2266628 TI - [A case of hemoptysis due to administration of an anti-thrombotic drug]. AB - A 63-year-old woman was referred to our division because of massive hemoptysis (200 ml) after administration of ticlopidine, an anti-thrombotic drug, for prevention of recurrent brain infarction. Ticlopidine treatment was stopped on the first hospital day, thereafter the patient's hemoptysis immediately disappeared. A chest roentgenogram and broncho-fiberscopic examination did not reveal any organic lesion associated with hemoptysis. Laboratory data revealed prolonged bleeding time and decreased platelet aggregation, suggesting that the patient had had a hemorrhagic diathesis associated with the administration of ticlopidine. Although many anti-thrombotic drugs have been recently employed in a variety of clinical cases, the patient's hemoptysis was considered to be due to side effects. PMID- 2266629 TI - [Squamous cell carcinoma of the lung detected during maintenance hemodialysis which reduced in size after combined CDDP chemotherapy]. AB - A 52-year-old man receiving maintenance hemodialysis for 6 years was referred to our division for further evaluation and additional therapy for cough and hemosputum lasting 2 months, and for examination of a chest roentgenographic abnormality. Transbronchial lung biopsy specimens revealed squamous cell carcinoma of the lung. A total of 8 courses of anticancer chemotherapy with 25-30 mg/m2 of CDDP performed biweekly resulted in a partial remission (56%) but no side effects, including gastrointestinal damage and agranulocytosis. Few cases of lung cancer receiving anticancer chemotherapy with CDDP during maintenance hemodialysis have been reported. Administration methods and dosage of CDDP for patients receiving maintenance hemodialysis were discussed. PMID- 2266630 TI - [A case of subacute necrotizing lymphadenitis with localized interstitial pneumonia]. AB - A 16-year-old male was admitted with a history of cervical lymph node swelling, high fever, cough and hemosputum. On admission, bilateral cervical lymph nodes swelling and fine crackles in the right lower lung field were noted. A chest X ray film showed an infiltrative shadow in the right lower lung field and right hilar enlargement. Cervical lymph node biopsy specimens revealed wide areas of necrosis with nuclear debris. Transbronchial lung biopsy showed infiltration of lymphocytes in the interstitium and bronchoalveolar lavage fluid showed increased T-lymphocytes and a decreased T4/T8 ratio. The patient was diagnosed to have subacute necrotizing lymphadenitis with T-lymphocyte alveolitis. Additionally, antinuclear antibodies were positive, and anti HTLV-I antibody was false positive. These findings suggested an immunological abnormality in this case. His cervical lymph node swelling and infiltrative shadow on chest X-ray film improved with steroid therapy. Our case may be the first case of subacute necrotizing lymphadenitis with T-lymphocyte alveolitis. PMID- 2266631 TI - [Two cases of mediastinal goiter with progressive deviation of the trachea by its growth and their thyroid hormone values in the fluid of the cystic lesions]. AB - We reported two operated cases (a 35-year-old male and 52-year-old male) of mediastinal goiter accompanied by marked tracheal deviation. The two patients did not have any clinical symptoms. CT, MRI, ultrasonography and angiography finding of the two cases are presented. Fluid was obtained from the cystic lesions by ultrasonically guided needle aspiration. The levels of thyroid hormones (T3, T4) in the fluid were not high in comparison with serum levels. Surgical resection was performed on the 35-year-old male case by collar incision and on the 52-year old male case by median sternotomy. PMID- 2266632 TI - [Desquamative interstitial pneumonia-like changes in idiopathic pulmonary fibrosis]. AB - A 61-year-old man was admitted to our hospital with fever, cough and dyspnea on exertion. The chest X-ray showed diffuse reticulo-granular infiltrates. Deterioration of clinical features and remarkable elevation of BALF lymphocytes (64.3%) suggested active interstitial pneumonia. The open lung biopsy specimen showed chronic interstitial pneumonia with DIP-like pathologic change. There was a remarkable clinical, physiological and roentgenographic improvement associated with decrease of BALF lymphocytes in response to steroid therapy. BAL is useful for monitoring disease activity and tapering steroids in patients with interstitial pneumonia who respond to steroid therapy. PMID- 2266633 TI - [A case of lung cancer suspected to be pulmonary mycosis of the fungus ball type]. AB - This paper reports a 73-year-old male case of lung cancer presenting as thin walled cavity which was suspected to be pulmonary mycosis of the fungus ball type. Routine chest X-ray film showed a thin-walled cavity without a round shadow inside it. CR tomogram taken 2 months after the previous plain chest X-ray film showed an irregular thickening of the cavity wall and a round shadow inside it. Pulmonary mycosis of the fungus ball type was suspected based on the CR tomogram. But chest X-ray CT film taken 1 month after the previous CR tomogram revealed that the entire cavity wall was thickened with irregular convexity and no round shadow was seen in the cavity. Cavitary lung cancer was also suspected based on the findings of X-ray CT film. The surgical specimen, obtained by right upper lobectomy, revealed a moderately differentiated squamous cell carcinoma unaccompanied by pulmonary mycosis in the cavity space. Even in cases suggestive of mycosis, aggressive surgical intervention is recommended in those suspected of malignancy. PMID- 2266634 TI - Emergency Nurses Association. Code of ethics for emergency nurses with interpretive statements. PMID- 2266635 TI - Presenting ... the ENA code of ethics. PMID- 2266636 TI - Designing an effective ED nursing quality assurance program. PMID- 2266637 TI - Leave the collar on. PMID- 2266638 TI - Behind the scenes of a tragic day. PMID- 2266639 TI - Suctioning a neonate: nose or mouth first? PMID- 2266640 TI - Case review. A 23-year-old man with an unusual impalement injury. PMID- 2266641 TI - Elective blood transfusions for AIDS patients in the emergency department: problems delineated and solutions and alternatives offered by quality assurance. PMID- 2266642 TI - On-site stat laboratory in the emergency department: implementation, advantages, and impact on care. AB - The goal of an emergency department is expendient quality care. The two aspects are expediency and quality. The goal is the same for both patient and staff. The ED stat laboratory makes the possibility of this goal a reality. PMID- 2266643 TI - Cruzan vs. Director, Missouri Department of Health: the recent Supreme Court decision and implications for emergency nursing. PMID- 2266644 TI - The effects of disasters on children: implications for emergency nurses. PMID- 2266645 TI - Nurse educator. Designing an orientation preceptorship: development, delivery, and evaluation. PMID- 2266646 TI - Hypothermia and the pediatric patient. PMID- 2266647 TI - Triage decisions. Difficulty in swallowing accompanied by fever in a 66-year-old man with a history of schizophrenia. PMID- 2266648 TI - Profiles: Leslee Stein-Spencer, emergency nurse, makes history in Illinois and the United States. PMID- 2266649 TI - The Joint's omissions. PMID- 2266650 TI - The twain meet. PMID- 2266651 TI - Practice guidelines: they are here. PMID- 2266652 TI - Determination of death. PMID- 2266653 TI - Who should deliver anesthetics? PMID- 2266654 TI - Theophylline toxicity. PMID- 2266656 TI - Adenosine for diagnosing wide-QRS tachycardia. PMID- 2266655 TI - MRI of brain abnormalities in Cockayne syndrome. PMID- 2266657 TI - Meta-analysis of data from experimental research. PMID- 2266658 TI - Experienced psychiatric nurses' prediction of inpatient aggression. PMID- 2266659 TI - Moral reasoning among female baccalaureate nursing students. PMID- 2266660 TI - Glomerular blood flow. PMID- 2266661 TI - Tumor necrosis factor induces contraction of mesangial cells and alters their cytoskeletons. AB - Cultures of human mesangial cells (MC) were established from the renal cortex of surgical specimen. The characteristic spindle-shaped or stellate appearance of MC was altered after treatment with tumor necrosis factor (TNF). After two hours, the MC retracted and lost reciprocal contacts. Furthermore, this treatment altered the cytoskeletal organization of MC, since a peripheral band of actin and stress fibers disappeared while the streaks of vinculin at focal contacts decreased. These changes were reversible when the MC were cultured in fresh medium. After five minutes of treatment with platelet activating factor (PAF), changes similar to those induced by TNF were observed. Inhibitors of PAF synthesis, such as plasma alpha 1-proteinase inhibitor and an anti-inflammatory peptide, blocked changes induced by TNF, PAF receptor antagonists inhibited changes induced by PAF and also by TNF. These results and the finding that MC are stimulated to produce PAF by TNF suggest that PAF is a secondary mediator of the changes in cell shape and cytoskeletal organization induced by this cytokine. PMID- 2266662 TI - Cytosolic calcium and protein kinase C reduce complement-mediated glomerular epithelial injury. AB - In rat membranous nephropathy, protein-uria is due to formation of the C5b-9 membrane attack complex of complement (C), and is associated with morphological evidence of glomerular epithelial cell (GEC) injury. Analogous morphological changes are induced by C5b-9 in cultured GEC. In addition, in cultured GEC C5b-9 induces Ca2+ influx, as well as Ca2+ mobilization and increased 1,2 diacylglycerol due to the activation of phospholipase C. In this study we investigated how this GEC activation pattern might influence C-mediated GEC injury. We demonstrate that the C5b-9-induced increase in cytosolic Ca2+ concentration ([Ca2+]i) did not impair ATP generation by mitochondria, suggesting that it does not contribute to cytotoxicity. Moreover, this increase in [Ca2+]i protected GEC from C-mediated cytolysis. However, a large increase in [Ca2+]i (produced by the Ca2+ ionophore A23187) impaired ATP generation and aggravated C mediated cytotoxicity, suggesting that intact mitochondrial activity is necessary for GEC to withstand C attack. Activation of protein kinase C (PKC) by phorbol myristate acetate (PMA) also decreased C-mediated cytolysis. Conversely, C lysis was enhanced in GEC that had been pretreated for 18 hours with a high dose of PMA to deplete PKC, and following PKC inhibition with H-7. Therefore, PKC activation, possibly resulting from C5b-9-induced increase in 1,2-diacylglycerol, triggered mechanisms that protected GEC from C-mediated injury. Thus, as a consequence of C5b-9-induced phospholipase activation, the amount of C-induced GEC injury is diminished. PMID- 2266663 TI - Nephron site responsible for the reduced kaliuretic response to mineralocorticoids during hypokalemia in rats. AB - Rats with hypokalemia induced by eating a low-K diet have a diminished kaliuretic response to mineralocorticoids. The purpose of this study was to determine if this was the due to a lower rate of net secretion of K in the cortical collecting duct (CCD) and/or an enhanced rate of reabsorption of K in the medullary collecting duct (MCD). Secondary active secretion of K in the CCD raises the [K] in the lumen as compared to the plasma [TF/P)K). If the (TF/P)K is greater than 1, there was secondary active secretion of K in this nephron segment. The (TF/P)K in the CCD was measured by microcatheterization of the collecting duct. Three groups of rats were studied: rats on a low-K diet with and without the acute administration of DOCA, and rats on a normal-K diet treated with DOCA on a chronic basis. Rats on the low-K diet had a (TF/P)K of 0.8 +/- 0.11; this value did not rise to values significantly greater than 1 after the acute administration of DOCA (1.4 +/- 0.35). In contrast, chronic administration of DOCA to rats fed a normal-K diet did result in a (TF/P)K which was significantly greater than unity (3.1 +/- 0.39). The degree of hypokalemia was not significantly different in these rats. The absolute and fractional reabsorption of K in the MCD was not different in the rats on the low-K diet with or without DOCA. We conclude that the nephron segment which is responsible for the reduced kaliuretic response to mineralocorticoids is the CCD. PMID- 2266664 TI - Arginine vasopressin gene expression in chronic cardiac failure in rats. AB - Arginine vasopressin (AVP) is known to be increased in patients and experimental animals with chronic cardiac failure (CCF). The importance of an increase in biosynthesis of AVP in the hypothalamus has, however, not heretofore been investigated and is the purpose of the present study. CCF secondary to infarction of myocardial tissue was induced by ligation of the left anterior descending coronary artery and sham operated animals served as controls. Four weeks later hypothalamic AVP mRNA was determined by solution hybridization using sense and anti-sense strand RNA. The blood pressure was lower in CCF than sham animals (131.2 +/- 3.1 vs. 112.8 +/- 4.0 mm Hg, P less than 0.05) and the total heart, and right and left ventricle weights were significantly higher in CCF rats. Plasma AVP was higher in CCF (sham 6.78 +/- 0.30; CCF 11.46 +/- 0.64 pg/ml, P less than 0.001) and plasma atrial natriuretic peptide was also higher in CCF than sham animals (205 +/- 36 vs. 554 +/- 56 pg/ml, P less than 0.001). The AVP mRNA in hypothalamus was significantly higher in CCF than sham animals (55.5 +/- 3.7 vs. 95.9 +/- 4.0 pg/micrograms total RNA, P less than 0.001). There was no difference in beta-actin mRNA in the hypothalamus of sham and CCF rats, indicating that the AVP-mRNA increase was specific in CCF. These results therefore demonstrate that increased AVP biosynthesis in the hypothalamus, in addition to release of the hormone from the posterior pituitary, may occur in CCF. PMID- 2266665 TI - Localization of 90-kDa heat shock protein in the kidney. AB - Antibody against 90-kDa heat shock protein (HSP 90) was produced in rabbits. The obtained antibody was highly specific to the antigen. Using the antibody, the intrarenal distribution of HSP 90 was studied in frozen sections of normal rat kidneys by fluorescent and enzymic immunohistochemistry. HSP 90 was predominantly present in the region from the distal convoluted tubule to the medullary collecting duct at a high intensity, and in glomerular podocytes and Bowman epithelial cells at a much lower intensity. Other segments of the nephron were stained little, even at a lower dilution of the antibody. Blood vessels and interstitial tissues were not stained. HSP 90 was localized in the cytoplasm and not in the nucleus. Moreover, immunohistochemical staining of HSP 90 showed greater intensity at the luminal side of the cells. These observations suggest that HSP 90 might play important roles in the kidney. PMID- 2266666 TI - Ureteric catheterization in the diagnosis of pyelonephritis--an experimental evaluation. AB - Experimental models of renal infections have been used to determine the accuracy with which the cellular and microbiologic components of ureteric and voided urine reflected the pathologic status of the kidney in pyelonephritis. In acute pyelonephritis, the composition of the ureteric urine reflected the pathologic status of the kidney, although in a few cases ureteric samples were either sterile or cell free. Animals with chronic pyelonephritis in which the lesions were either infected or sterile commonly had sterile ureteric urine. Pyuria, however, was demonstrable in both these situations. In subclinical pyelonephritis, ureteric samples from infected kidneys were variably culture positive, although pyuria was a common observation. Discriminate function analysis based on actual renal status and ureteric data gave an overall correct classification rate of 67% and demonstrated at least 80% agreement in four of the five classification groups. PMID- 2266667 TI - Effects of probucol on renal function in rats with bilateral ureteral obstruction. AB - To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex. PMID- 2266668 TI - Three-dimensional morphometric analysis of segmental glomerulosclerosis in the rat. AB - In idiopathic nephrotic syndrome, and in experimental models of nephrosis, changes of visceral epithelial cells involve the entire glomerular population while segmental sclerotic changes are reported to affect only a certain number of glomeruli. Because conventional determination of the percentage of glomeruli affected by sclerotic lesions is usually based on the examination of randomly selected sections, we wondered whether glomeruli appearing normal in a given section could be affected by sclerosis in other regions of the capillary tuft (CT). To assess the real incidence and the spatial extension of sclerotic changes at the level of single glomerulus, we used serial-section morphological analysis to measure the volume of the glomerulus and that of sclerosis lesions. In glomeruli from control rats and in glomeruli from adriamycin (ADR) treated rats surface area of Bowman's capsule (BC), CT and sclerotic regions were measured using stereology techniques in all the consecutive sections containing each individual glomerulus, and corresponding volumes were then calculated. Mean volume of BC and CT were not significantly different between control and ADR rats (0.71 +/- 0.03 and 0.53 +/- 0.03 vs. 0.76 +/- 0.04 and 0.53 +/- 0.02 microns 3 x 10(-6), respectively). The distribution of glomerular volume parameters in the ADR rats were more spread out than in control animals, indicating that some glomeruli became smaller while other became larger. No sclerotic changes were found in control rats, while in the three ADR rats 94, 90 and 92% of glomeruli, respectively, were affected by sclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266669 TI - Tracer kinetics and actions of oral and intraperitoneal 1,25-dihydroxyvitamin D3 administration in rats. AB - Tracer kinetic parameters of [3H]-1,25(OH)2D3 were calculated from data obtained following its acute oral (p.o.) or intraperitoneal (i.p.) administration. In normal rats studied after the tracer had distributed into the body, the slope and intercept of the log-serum [3H]-1,25(OH)2D3 versus time relationship were not significantly influenced by the route of administration. Pretreatment with 1,25(OH)2D3 (0.2 micrograms/100 g/day) by the same route as the tracer resulted in the following changes: in p.o. rats the serum [3H]-1,25(OH)2D3 intercept was much lower but the slope was not changed; in i.p. rats the intercept was not changed but the slope was increased. Both p.o. and i.p. treatment with 1,25(OH)2D3 lowered the weight gain and diet consumption, and increased serum calcium, kidney tissue calcium and urinary excretion of orally administered 45Ca. All the measures of bioactivity were greater in the i.p. dosed rats than in the p.o. dosed rats. We conclude that the p.o. 1,25(OH)2D3 was less potent because of diminished bioavailability due to self induction of its presystemic metabolism and inactivation. PMID- 2266670 TI - Glomerular angiotensinase A in the rat: increase of enzyme activity following renal ablation. AB - Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 weeks after 1-1/3 nephrectomy. Glomerular ATA activity in remnant kidneys increased significantly after five weeks following ablation compared with glomeruli of two kidney control rats (5.34 +/- 4.02 vs. 1.71 +/- 1.96 mU/mg protein, P less than 0.05). After 14 weeks, however, this difference was no longer present. Treatment of rats with enalapril or saralasin inhibited the increase of ATA seen five weeks after renal ablation, whereas indomethacin had no effect on enzyme activity. Furthermore, normal two kidney rats, treated with furosemide, revealed a higher glomerular ATA than two kidney controls (5.5 +/- 2.64 vs. 2.1 +/- 1.7 mU/mg protein, P less than 0.05). In vitro superfusion of isolated glomeruli with enalaprilate or furosemide from rats after renal ablation did not influence enzyme activity, however, superfusion with 0.05 mM angiotensin II or 0.05 mM saralasin significantly reduced ATA. Our results suggest that glomerular ATA might be involved in the early regulation of the intrarenal renin angiotensin system and could modify glomerular adaptation to reduce renal mass by affecting angiotensin II degradation. PMID- 2266671 TI - Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. AB - We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients. PMID- 2266672 TI - Congenital hepatic fibrosis in autosomal-dominant polycystic kidney disease. AB - Congenital hepatic fibrosis was found in four families with autosomal-dominant polycystic kidney disease. Congenital hepatic fibrosis is commonly though to be characteristic for autosomal-recessive polycystic kidney disease, but the reported families, show that it can also complicate autosomal-dominant polycystic kidney disease. In three families close linkage between the mutation causing the disease and DNA markers on chromosome 16 was demonstrated. The clinical course of the congenital hepatic fibrosis differed considerably; in one family the children with congenital hepatic fibrosis died soon after birth, in the three other families an approximately 20 years follow-up showed no detectable progression of the liver disease. PMID- 2266673 TI - L-lactate high-efficiency hemodialysis: hemodynamics, blood gas changes, potassium/phosphorus, and symptoms. AB - Hemodynamic changes were measured during high-efficiency hemodialysis (HEHD) using three dialysis solutions: L-lactate (46 mM), bicarbonate (35 mM + 4 mM acetate), and acetate (39 mM). Cardiac output was determined by changes in thoracic electrical bioimpedance. Although there appeared to be subtle differences in hemodynamic response to L-lactate versus bicarbonate, the blood pressure, cardiac output, and total peripheral resistance were affected less with either of these solutions than with acetate. In particular, neither L-lactate nor bicarbonate HEHD were associated with a change in cardiac output, whereas with acetate HEHD a marked (22%) increase in cardiac output was seen concurrently with a moderate fall in blood pressure and TPR. Both acetate and L-lactate HEHD were associated with hypoxemia, whereas with bicarbonate HEHD the PO2 did not change. With L-lactate HEHD, correction of pH and plasma HCO3 concentrations was delayed but these values were not significantly different from those obtained with bicarbonate HEHD by one hour after dialysis. Potassium removal was comparable with the three dialysis solutions. Phosphorus removal with L-lactate tended to be slightly less than with bicarbonate, but not less than with acetate. Our results suggest that L-lactate (46 mM) dialysis solution may be a suitable alternative to acetate for HEHD, being associated with a hemodynamic profile that is similar to that of bicarbonate and better than that of acetate. Our results further suggest that the hypoxemia associated with the use of acetate dialysis solution is not intrinsic to acetate, but is due either to a low dialysis solution PCO2 level or to accelerated consumption of oxygen during substrate metabolism. PMID- 2266674 TI - Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. AB - Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles. PMID- 2266675 TI - Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects. AB - Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266676 TI - Effects of recombinant human erythropoietin on cerebral and cutaneous blood flow and on blood coagulability. AB - Seizures, hypertensive encephalopathy, transient ischemic attacks, and thrombosis of hemodialysis accesses occurred in early clinical trials with recombinant human erythropoietin. To determine if these events may be caused by the increased hematocrit value or some direct effect of the recombinant human hormone, 10 transfusion-dependent hemodialysis patients were divided into two groups of five according to their serum ferritin concentration: group A. less than 800 microgram/liter, and group B. greater than 800 micrograms/liter. After a month of placebo administration, recombinant human erythropoietin was given (150 U/kg intravenously thrice weekly) for four months and then stopped for one month. Hematocrit values were maintained at 0.33 +/- 0.02 (mean +/- SD) by dose adjustment in group A and at 0.26 +/- 0.02 by thrice weekly phlebotomies in group B, who received a constant dose of erythropoietin. Viscosity increased from subnormal to normal in group A (P less than 0.02) and cerebral blood flow decreased from above normal to normal (P less than 0.02). In group B minor, statistically insignificant, changes in viscosity and reciprocal changes in cerebral blood flow also occurred. There was no change in either group in transcutaneous oxygen tension. Bleeding time decreased toward normal in both groups during recombinant human erythropoietin administration but the changes did not reach statistical significance. Fibrinogen levels were increased in all patients but remained unchanged. No other significant coagulation-related changes were observed. Recombinant erythropoietin in the dosage and schedule of administration described in this study did not lead directly or indirectly to changes likely to precipitate seizures or intravascular thrombosis. PMID- 2266677 TI - Gene mapping in Alport families with different basement membrane antigenic phenotypes. AB - The present study was undertaken to determine whether differences among Alport kindreds in the antigenic phenotypes of their basement membranes result from defects at distinct genetic loci or from allelic mutations at a single locus. We analyzed linkage of the Alport gene to polymorphic loci on the X chromosome in three families with Alport syndrome. In two of the families, epidermal basement membranes of affected members showed altered immunohistologic reactivity with a discriminating antibody (FNS1) that identified a 26 kD peptide in the NCl domain of basement membrane collagen. In the third family epidermal basement membranes of affected individuals reacted normally with the antibody. The disease gene mapped to the Xq21-q22 region of the long arm of the X chromosome in the two families with altered basement membrane antigenicity and in the family with normal basement membrane antigens. We conclude that Alport syndrome in each of these kindreds arose from allelic mutations at a single genetic locus, although we cannot at this time exclude the possibility that two or more tightly linked genes are involved. As the genes for the known chains of type IV collagen are on chromosome 13, our findings suggest that the Alport gene may encode a new basement membrane collagen chain. PMID- 2266678 TI - Soft tissue calcification in pediatric patients with end-stage renal disease. AB - Soft tissue calcification is a recognized complication of uremia in adult patients and has been implicated as a cause of ischemic necrosis, cardiac arrhythmias, and respiratory failure. However, soft tissue calcification has been regarded as rare in pediatric renal patients. Following a sudden death due to pulmonary calcinosis in an adolescent after renal transplantation, we retrospectively reviewed clinical, biochemical and autopsy data of 120 patients with uremia, on dialysis, or following renal transplantation cared for at Childrens Hospital of Los Angeles from 1960 to 1983. Soft tissue calcification was found in 72 of 120 patients (60 percent). Forty-three patients (36 percent) had systemic calcinosis (Group A): the most frequent sites of mineral deposition were blood vessels, lung, kidney, myocardium, coronary artery, central nervous system, and gastric mucosa. Vascular calcification was uniformly accompanied by deposits in other organs. Twenty-nine patients had small amounts of focal calcification (Group B) and 48 patients had no soft tissue calcification (Group C). By multiple logistic regression analysis, the use of vitamin D or its analogues, the form of vitamin D medication prescribed, the peak calcium x phosphorus product, the age at onset of renal failure, and male sex were jointly associated with calcinosis (Group A). Vitamin D therapy showed the strongest independent association with calcinosis and the probability of calcinosis was greater in patients receiving calcitriol when compared with dihydrotachysterol and vitamin D2 or D3. The duration of renal failure, peak serum calcium, serum calcium at death, serum phosphorus at death, and primary renal diagnosis, were not statistically associated with calcinosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266679 TI - Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. AB - The risk of aluminum (Al) accumulation in patients with chronic renal failure has led to use of non-Al phosphate binders. Frequently, Al and non-Al phosphate binders are co-administered. Unfortunately, calcium citrate (Ca citr), when given with Al-gel, markedly enhances Al absorption. To determine whether calcium acetate (Ca acetate) also augments Al absorption, 10 normal volunteers were each given orally, three-day courses of the following drug combinations dosed four times daily: 1) aluminum hydroxide gel (Al[OH]3) (5 ml) alone; 2) Al[OH]3 (5 ml) plus Ca acetate (1330 mg); 3) Al[OH]3 (5 ml) plus Ca citr (950 mg). A nine day wash-out occurred between each course. Al levels were measured using flameless atomic absorption spectrophotometry. Daily urine Al excretion was measured during a two-day baseline before each course and during each three-day drug course. Plasma Al was obtained during each baseline and drug course. Mean 24-hour Al excretion (micrograms/g creatinine/day) at baseline versus treatment for each combination was: 1) 5.9 +/- 3.2 versus 42.0 +/- 40.7 (mean +/- SD); 2) 5.7 +/- 3.0 versus 40.3 +/- 28.6: 3) 6.3 +/- 3.4 versus 175.8 +/- 103.3. Al excretion was significantly greater with combination 3 than with either 1 or 2 (P less than 0.05). The difference between 1 and 2 was not significant. Plasma Al (micrograms/liter) at baseline versus treatment for each combination was: 1) 5.3 +/- 4.2 versus 8.1 +/- 2.5 (mean +/- SD); 2) 3.1 +/- 2.2 versus 7.3 +/- 2.9; 3) 3.0 +/- 2.3 versus 12.0 +/- 6.1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266680 TI - Early and late adjustment to potassium loading in humans. AB - We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intake) was achieved in the second 24 hour period of K loading. This was associated with elevated plasma K and aldosterone, slightly negative sodium (Na) balance and stimulated plasma renin activity. At 20 days of K loading Na loss had been compensated. Plasma renin activity and aldosterone had returned to baseline, although the latter kept increasing after each single K meal. Compared to the first K meal, the K meals at 72 hours and 20 days of K loading were followed by more kaliuresis, while the natriuretic effect had disappeared. Abrupt discontinuation of K loading was followed by negative K balance, lasting only 24 hour, and by Na retention, lasting 72 hours. In conclusion, switching to a high K diet in humans is immediately followed by increased renal K excretion, and by Na loss. K excretion increases over a few days, while Na loss is halted. This can be explained by the rise in plasma aldosterone, secondary to elevated plasma K and renin activity. After weeks, renal adaptation forms an additional factor promoting K excretion and preventing natriuresis. The latter appears specifically from the Na retention which occurs after discontinuation of K loading in the absence of persistent aldosterone stimulation. PMID- 2266681 TI - Effects of dialysis membranes on beta 2-microglobulin production and cellular expression. AB - We investigated the effects of different dialysis membranes on the production of beta 2-microglobulin (beta 2m) in peripheral blood mononuclear cell cultures (PBMNC) obtained from hemodialysis patients in a prospective cross-over design study. Chronic dialysis with cuprophane membrane leads to an increase in beta 2m production from 129 +/- 11 ng/ml to 192 +/- 23 ng/ml (P less than 0.002). This increase is reversed by the use of a non-complement activating membrane polymethylmethacrylate. In addition, during chronic dialysis with cuprophane membrane, an increasing proportion of these cells display low beta 2m expression on their surface (from 6.1 +/- 0.8% of PBMNC to 16.9 +/- 3.4%, P less than 0.001), concomitant with the emergence of cells with low density of HLA on their surface (from 4.9 +/- 1.2% of cells to 32.9 +/- 7.8% of cells, P less than 0.001). The total content of cell-associated beta 2m is also decreased in dialysis patients in general, and in particular in patients chronically dialyzed with new cuprophane membrane. These effects can be reproduced by incubation of PBMNC with cuprophane membranes, and with the addition of C5a, IL-1 and TNF in vitro. Thus, chronic dialysis with cuprophane membrane may be a factor in the genesis of high beta 2m levels and causes changes in beta 2m and HLA expression on cell surfaces. PMID- 2266682 TI - Development of a new radioimmunoassay for erythropoietin using recombinant erythropoietin. AB - The development of a 24 hour radioimmunoassay for erythropoietin (EPO) using EPO derived from recombinant DNA as both immunogen and ligand is described in the present paper. Mixed breed rabbits immunized with 10 micrograms/kg of EPO derived from a stably transfected cell line (Elanex Pharmaceuticals Inc., Bothel, Washington, USA, through McDonnell Douglas Corp., St. Louis, Missouri, USA; "MD") produced antibodies to EPO with high titer (up to 1:896,000 final dilution in the tube), high affinity (8.4 x 10(11) liter/M), and good specificity. Purified EPO from the above source or from AmGen Biologicals (Thousand Oaks, California, USA; "AG") were successfully radioiodinated with the chloramine-T method and used as ligand in the radioimmunoassay. Standard dose-response curves prepared with EPO from both commercial sources were not significantly different and showed a sensitivity of 0.75 to 0.96 mU/tube. The dose-response curves in both systems also showed parallelism with serially diluted serum from a patient with aplastic anemia. Within-assay and between-assay precision were determined by assaying multiple replicates of a serum pool. Recovery of exogenous EPO added to a serum pool averaged 97% for both systems. The range of normal human serum EPO was determined by assaying the sera of 153 hematologically-normal adult subjects and was found to be 1.1 to 27.3 mU/ml for MD EPO and 0.5 to 16.7 mU/ml for AG EPO. Sera from several patients with hematologic abnormalities were also assayed, including those of 36 patients with anemia of end-stage renal disease (mean +/- SEM, 29.5 +/- 4.0 mU/ml; P less than 0.01). In conclusion, this new, more rapid and sensitive radioimmunoassay system can be used to measure EPO levels in sera from normal human subjects and patients with several types of anemia, and should also be very useful in therapeutic drug monitoring of patients receiving EPO from various commercial sources. PMID- 2266683 TI - Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. PMID- 2266684 TI - Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. AB - We report five life-threatening anaphylactoid reactions occurring within the very first minutes of hemodialysis on polyacrylonitrile (AN69) capillary dialyzers in three patients receiving ACE inhibitors. Such reactions were not observed either in patients treated with ACE inhibitors but dialyzed on other membranes (N = 9), nor in patients on AN69 who did not receive ACE inhibitors (N = 19). These anaphylactoid reactions could be due to bradykinin accumulation, as a result of both increased synthesis--by interaction of blood with the AN69 polymer--and catabolism blockade by ACE inhibitors. PMID- 2266685 TI - Creation of a functioning chimeric mammalian kidney. AB - The possibility of adding new nephrons to the mammalian kidney was studied. Embryonic metanephric tissue was implanted into the renal cortex of neonatal mice less than 24 hours old, and the development of the chimeric kidney was followed over the following two to four weeks. Donor tissue was obtained from the homozygous beige mouse and a mouse line transgenic for the beta-globin gene, which provided distinct cellular and nuclear markers which were used to distinguish donor from recipient nephrons. Differentiation and growth of donor nephrons occurred in the host kidney and included vascularized glomeruli, mature proximal tubules, and tubular extensions into the renal medulla. Glomerular filtration was demonstrable in donor nephrons using FITC-dextran as a marker of filtration into the proximal tubules. Transplantation of metanephric tissue into adult mouse kidneys did not lead to glomerular or tubular differentiation. This study demonstrates the feasibility of adding functioning nephrons to mammalian kidneys in species in which there is ongoing nephrogenesis post-natally. PMID- 2266686 TI - ANCA-associated renal disease. PMID- 2266687 TI - [Vitrectomy in the treatment of epimacular membranes (macular pucker)]. AB - The formation of contractile membranes on the inner retinal surface of the macula (macular pucker, epiretinal gliosis) has an increased incidence with age. They also occur in vascular or inflammatory disorders of the posterior segment, after blunt injuries, retinal detachment surgery, and coagulation therapy. Surgical removal of epiretinal membranes in the macula by vitrectomy is performed since 1978. Our analysis of 78 consecutive patients with a postoperative follow-up from 6 to 36 months showed good anatomical and functional results. Visual impairment caused by metamorphopsia decreased in all patients. Visual acuity improved two lines or more in 55 cases (70.5%). 22 (28.2%) were unchanged (including improvement of one line), and one eye (1.3%) became worse. Functional results were significantly better in eyes with macular pucker of less than 6 months duration and with thin, transparent membranes. The age of patients is not likely to play a significant role for functional outcome. Complications were cataracts in 10, retinal defects or detachments in 5 patients, and recurrence of the epiretinal membrane in 2 cases. PMID- 2266688 TI - [Value of vitrectomy and lensectomy in the treatment of complicated cataracts and complications of eye injuries]. AB - Vitrectomy and/or lensectomy was performed in 33 successive cases of traumatic and complicated cataracts. The discussed cases were divided into 2 groups: 1. late reconstructions of the anterior eye segment after injuries and 2. complicated cataracts. After surgery the visual acuity amounted 6/60 or better in 27 from 33 eyes (81.8 per cent). Full visual acuity was attained in 18 patients (54.5 per cent). PMID- 2266689 TI - [Vitreous body proteins. III. Immunoelectrophoresis of the vitreous body in pathological conditions of the eye]. AB - Presented and discussed were the immunoelectrophorograms of the vitreous in various pathological conditions of the eye. The antigenic similarity of the serum and vitreous proteins were established; the quantitative and qualitative changes of protein fractions in some pathological conditions were demonstrated. PMID- 2266690 TI - [Prevention of retinal detachment. I. Cryopexy before cataract extraction. Preliminary report]. AB - The authors discuss the results of cryopexy applied prophylactically in 32 eyes. The freezing was executed at least 6 weeks before the cataract extraction in eyes endangered by retinal detachment. This were the high myopia eyes, so called fellow eyes and eyes in persons aged between 30 and 40 years. Retinal detachment did not occur in either of the observed eyes in the period of 1-5 years. PMID- 2266691 TI - [Cystoid macular edema in pseudophakia]. AB - One hundred and eighty six patients (217 eyes) after cataract extraction with intraocular lens implantation were analyzed in search of cystoid macular oedema. In general--9 cases of cystoid macular oedema were found, among them 5 patients after intracapsular cataract extraction with implantation of an anterior chamber lens (9.8 p.c.) and 4 after extracapsular cataract extraction with implantation of a posterior chamber lens (2.7 p.c.). One could observe a beneficial influence of a prophylactic application of indomethacin compounds in order to lessen the incidence of the macular oedema. PMID- 2266692 TI - [Retinal detachment in pseudophakia]. AB - Retinal detachment in an aphakic eye is a grave therapeutical problem. There exists some fears that cataract extraction with implantation of an artificial lens may increase the number of these complications. Three hundred and seventy cases of cataract extraction with implantation of an artificial lens performed in our department were analysed from the point of view of the incidence of retinal detachment. The cataract was extracted extra- and intracapsularly and the artificial lens was implanted in the anterior as well as in the posterior chamber. During the period of observation--4 months to 3 years--it was established that the number of the retinal detachment in pseudophakia was not larger than in aphakic eyes without implant. PMID- 2266693 TI - [Effectiveness of laser therapy in retinal vein thrombosis]. AB - The authors compared the results of treatment in a group of patients (1st group- 20 persons) with a retinal vein thrombosis with a second group (24 persons--25 eyes) treated pharmacologically with a simultaneous laser photocoagulation performed by argon and crypton lasers. Improvement of the visual acuity in late observations was established in 40 per cent of eyes of the 1st group and in 64 per cent of the 2d group; worsening was observed in 55 per cent of eyes of the 1st group and in 8 per cent of the 2d group. The authors consider that an early applied laser photocoagulation is beneficial in the treatment of the retinal vein thrombosis and besides that pharmacological treatment coupled with laser photocoagulation gives much better results than the pharmacotherapy alone. PMID- 2266694 TI - [Use of sodium hyaluronate in the treatment of retinal detachment with poor prognosis]. AB - Sodium hyaluronate was applied intravitreally in 7 cases for the apposition of large balloon-like retinal detachments. The clinical results were very satisfactory, they speak for the usefulness of application of this compound. PMID- 2266695 TI - [12-year observation of atypical retinitis pigmentosa]. AB - Analysis of the clinical course of retinal degeneration in 40 patients in whom one suspected a retinal dystrophy "sine pigmento", a sector or unilateral dystrophy or a mixed conerod form. Eventually the diagnosis was possible only after performing a complex of investigations: the visual acuity, visual field, adaptation, the ERG and in some cases also the fluorescein angiography. No exact correlation between the results of a particular test could be established but the degree of abnormality of some of them was decisive for the moment of the first reference of the patient for examination by an ophthalmic specialist. In the course of observation the progress of the condition was evident but the dynamics of it was not the same and it was dependent on many factors. PMID- 2266696 TI - [Vitrectomy in the early treatment of extensive penetrating eye injuries. Comparative studies]. AB - Presented are early and late results of treatment of extensive perforating eye injuries treated by vitrectomy immediately after the patient reported for a hospital treatment. For comparison--a similar group of patients with corresponding posttraumatic lesions was selected; they were treated by traditional methods and in some cases also by vitrectomy but performed only for the treatment of late complications. The results obtained confirm the necessity of early vitrectomy as a method of reconstruction of the anatomical conditions after an extensive perforating injury. PMID- 2266697 TI - [Possibilities of the treatment of senile retinoschisis]. AB - Photocoagulation and cryopexy were applied in 5 patients with retinoschisis; in 3 they were connected with a temporary invagination of the sclera by means of a Lincoff-Kreissig balloon. After the photocoagulation the authors attained the control of the increase of schisis in 3 patients; in 1 woman-patient a progress of pathological changes was seen. Cryopexy connected with a temporary invagination lead to a good result in a case not formerly treated. The same method in patients treated before by the photocoagulation of the detachment area was definitely less effective. It was suggested that the use of invagination and pressure upon the eye after the break of the choroi-retinal barrier may speed-up the absorption of the fluid from schisis cavity. PMID- 2266698 TI - [Pre- and postoperative management of patients with retinal detachment]. AB - Our procedure in both these periods is discussed in reference to the immobilization of the patient in bed, immobilization of the eyes, the period of the treatment depending on the extent of the detachment, the localization of the tears and application of surgical methods. It enabled us to shorten the period of treatment of the non-complicated cases from 62 days in 1962 and 49 days in 1968 to 12 (in cases of single operation) and to 26 days (in cases of multiple operations) in the years 1986-87 including numerous laboratory examinations. PMID- 2266700 TI - [Vitrectomy in the treatment of vitreous body prolapse after cataract extraction]. AB - Vitreous prolapse into the anterior chamber after cataract extraction is a severe complication in cases in which there is a contact between the vitreous and the cornea. The present paper discusses the result of treatment by vitrectomy in 15 patients with this complication. Anatomical and functional improvement was attained in 12 cases (89 p.c.) and in 5 among them--full visual acuity was obtained. PMID- 2266699 TI - [Results of the treatment of infectious endophthalmitis by vitrectomy]. AB - Infective endophthalmitis is a severe ophthalmological condition and may occur as a consequence of a perforating injury or of a surgical procedure. The paper presents personal results of treatment of this disease with the use of vitrectomy and application of intraocular antibiotics. The visual acuity after completion of the treatment was 6/6 to 6/8 in 35.7% of cases. Besides--contemporary opinions on the treatment of infective endophthalmitis are presented on the basis of experience and data from the literature. PMID- 2266701 TI - [Abdominal Doppler sonography in childhood]. AB - With the help of pulsed Doppler sonography and colour coded Doppler sonography noninvasive measurements of blood flow within the abdominal vessels are possible. Cystic and tubular abdominal masses and vascular structures can be differentiated. Laminar and turbulent flow as well as arterial and venous flow can be distinguished. The direction of blood flow can be shown. Regarding liver circulation Doppler sonography of portal hypertension, portal vein thrombosis, veno-occlusive-disease, Budd-Chiari-Syndrome and transplant rejection or other vascular complications after liver transplantation can be shown. The circulation of the spleen should be examined if aneurysms, thrombosis or portal hypertension are suspected. Mesenterial circulation should be investigated in suspected vascular occlusion, arterial stenosis and necrotizing enterocolitis. Renal Doppler sonography is helpful for the diagnosis of renal artery stenosis, arterio venous fistulas, renal vein thrombosis and acute transplant rejection. PMID- 2266702 TI - [Continuous Doppler sonography: a new method in the monitoring of the cerebral circulation in very small premature infants]. AB - Disorders of cerebral circulation, which are a major risk factor of intracerebral haemorrhage in the preterm baby, can be recognized by Doppler sonography. The development and clinical application of a small miniature Doppler transducer (13 x 9 x 20 mm) is presented which can be fixed onto the infant's fontanel. It is suitable for continuous measurements with a low energy output of only 13 mW. PMID- 2266703 TI - [7-week-old infant with a hydrolethalus syndrome: case report, differential diagnosis and literature review]. AB - We report on an 7 weeks old male infant with hydrocephalus internus, dysplastic low-set ears, micrognathia, vitium cordis, hypogenitalism, and polyhydramnios in pregnancy. The variability of the Hydrolethalus syndrome will be demonstrated. Our patient shows, that this syndrome is not a lethal in all cases. We report on an 7 weeks old male infant with hydrocephalus internus, dysplastic low-set ears, micrognathia, vitium cordis, hypogenitalism, and polyhydramnios in pregnancy. PMID- 2266704 TI - [The diagnosis of sleep apnea--possibility for the prevention of SID?]. AB - Groups of children with a statistically enhanced risk for SIDS: siblings of SIDS victims and other full-term and preterm infants with anamnestic signs for an enhanced risk of SIDS and a control group of healthy infants without anamnestic signs of risk were polysomnographically investigated in the first year of life. The mean apnoea duration (MA-value estimated by frequency and length of apnoeas greater than or equal to 3s) in the sleep states active and quiet sleep was calculated. During active sleep there is a significant inverse correlation between MA and postnatal age in the full-term and preterm SIDS-risk infants but not in the controls and siblings of SIDS-victims. In all age groups there are some children in the full-term and preterm infants with extremely enhanced MA values. For 6 age groups of the first year of life the 90% percentile of the MA value was calculated separately in the sleep states active and quiet sleep to select infants with an abnormal breathing pattern. This limit could be a help for the decision on therapy. PMID- 2266705 TI - [Intrathecal production of neopterin in meningitis in childhood]. AB - A major activator of antigen presenting cells (APC) is gamma interferon a product of activated T-lymphocytes. CNS is not well studied and represents a unique system with respect to the immune reactions. Neopterin is an indirect marker of gamma interferon deliberation and may give some new information on the role of APC in CNS. Neopterin in serum and cerebrospinal fluid (CSF) was determined by specific RIA in children who were lumbar punctured to exclude meningitis. Neopterin was found in various concentrations in serum and CSF of all patients (n = 47). Bacterial meningitis (group 3) was diagnosed in 12 and aseptic meningitis in 18 children (group 2). CSF was drawn in 17 children with febrile convulsions (group 1). Elevated serum neopterin in childhood was only reported in children with an atypical PKU, while data on CSF neopterin were published only in a few cases of adults with CNS involvement. The results show that the APC is stimulated rapidly in childhood similar as in adults following severe viral or bacterial infections. Furthermore neopterin in CSF is not only explained by alteration of the blood-brain barrier but also it may reflect local intrathecal response with activation of accessory cells (APC) in the CNS itself. Between the stimulation of the cellular immune system indicated by increased levels of neopterin and the severity of the disease seems to be a positive correlation. PMID- 2266706 TI - [Experiences with ambulatory long-term blood pressure measurement in childhood and adolescence]. AB - In a period of more than 2 years experiences with ambulatory blood pressure monitoring (ABPM) in children and adolescents aged from 2 years onward were collected, and practicability and clinical possibilities of diagnostic use were examined. We used the Medilog-ABP apparatus (Oxford Medical, Oxford Instruments Group P.L.C.), which functions fully automatically by the auscultatory method. The following results can be stated: 1. ABPM is accepted very well by young patients. Disturbances of normal behavior or sleep occurred in only 10% of the cases. 2. The rate of fault values in ambulatory long-term use is about 30%, by which useful diagnostic information is guaranteed. 3. By invasive and non invasive parallel measurements a good validity of the values could be proved. 4. The amount of information provided by this method must be considered very great in clinical questions. ABPM allows a detailed evaluation of circadian blood pressure patterns, and an individual adjustment of circulation therapies. According to our experiences ambulatory blood pressure monitoring thus represents an enrichment of circulation diagnostics in pediatrics. PMID- 2266707 TI - [Hydrogen (H2) breath test following lactose loading in children with recurrent abdominal pain]. AB - To define the practical diagnostic value of H2 breath testing after lactose load in children with chronic abdominal pain, we measured end-expiratory H2 every 30 minutes for 2 hours after peroral lactose (2 g/kg body weight, Lactoscreen). H2 testing was done in 62 children (28 female, 32 male), aged between 2 and 16 years. Abdominal pain had been observed in these children for more than 2 months. Causes of abdominal pain other than lactose intolerance had been excluded. In 2 out of 62 children, H2 testing was impossible for lack of cooperation. 17 out of the remaining 60 children showed a positive test result (28.3%). In 15 patients, the rise in H2 exceeded 40 ppm, and was thus easily distinguished from a nonspecific rise (less than 25 ppm). Stool pH and Clini-test results were not correlating well with H2 findings, In 16 out of 17 children with positive H2 tests, abdominal pain had ceased on a diet free of lactose after a month. After 6 months 15 out of 17 children were symptom free. These data confirm early indication of non-invasive H2 testing in children with chronic abdominal pain. PMID- 2266708 TI - [Age-specific and sex-specific reference values for the excretion of free amino acids in the 24-hour urine of children]. AB - Free amino acids were determined quantitatively by ion exchange column chromatography in 24 h urine of 354 (male = 187, female = 167) "healthy" infants, children and adolescents. Urine was deproteinised by 5% sulphosalicylic acid (1:1, v/v). The results - 95% confidence range - are presented age-dependent (groups: up to 1 month, 1-24 months, 2-6 years, 6-10 years, 10-14 years) and sex dependent in table 3 and 4. PMID- 2266709 TI - [Fanconi-Bickel syndrome]. AB - The Fanconi-Bickel syndrome is characterized by tubular dysfunction, impaired metabolism of glucose and galactose and glycogenosis. Up to now the data of nineteen patients have been reported. In the following case firstly an abnormal body composition is described measuring the concentration of Potassium-40 with a Whole Body Radiation Counter. Before therapy an increased value of total body cell mass but no value of total body fat is measured. After therapy body weight increased while cell mass decreased and a value of fat had been observed. Concerning renal parameters a 60 fold elevation of the beta 2-microglobulin clearance is noted. PMID- 2266710 TI - [D-penicillamine-induced IgA deficiency in the therapy of Wilson's disease]. AB - Serum IgA deficiency was first noted in a 10 year old boy 8 months after the onset of D-penicillamine therapy. Special immunological examinations revealed a deficiency of the secretory component of IgA while cellular functions of T- and B lymphocytes were normal. The patient showed discrete clinical signs compatible with IgA deficiency. Regular control of patients with Morbus Wilson and D penicillamine treatment should include measurement of serum immunoglobulin levels. PMID- 2266711 TI - [Facial paralysis in a 2 1/2-year-old girl due to herpes zoster oticus. Results of the reactivation of a chickenpox infection in infancy]. AB - A case of herpes zoster oticus in a 2 1/2 year-old girl with a history of varicella at the age of 4 months is reported. Peripheral facial palsy was the prominent clinical symptom. Following treatment with Acyclovir 15 mg/kg/day i.v. for 7 days a complete remission was noted. Course, treatment and prognosis of zoster oticus are discussed, as well as the increased incidence of herpes zoster in children who had varicella before the age of 1 year. PMID- 2266712 TI - [Toxic shock syndrome]. AB - We report about a one year old girl with toxic shock syndrome (TSS), which was confirmed by a significant rise of TSST-1 titers. In addition to known manifestations of TSS, to our knowledge this is the first report about development of polyserositis in this disease. Tumor necrosis factor (TNF) was elevated at initial evaluation and fell under treatment with cortisone. This finding is in contrast to in-vitro observations. We believe that the use of cortisone in TSS warrants further investigation. PMID- 2266713 TI - [Hemophagocytic syndrome in childhood]. AB - Disorders of the histiocyte-macrophage system in childhood comprise a manifold variety of clinical entities. The basic immunopathological mechanisms have still not been clarified in detail. We report on a 15 months old Yugoslavian boy of non consanguineous parents, who developed persistent high temperatures and bloody diarrhoea at the age of 11 months, followed by a rapidly progressive dystrophy, hepatosplenomegaly and peripheral pancytopenia. An extensive virological, bacteriological and protozoal diagnostic program failed to reveal a pathological result. A bone marrow aspiration showed an extremely hypocellular marrow without infiltration of pathological cell populations. In spite of extensive supportive care and systemic steroid therapy, the patient died by bleeding complications due to severe untreatable thrombocytopenia. In post-mortem-biopsies a marked infiltration of RES-organs (lymph nodes, liver and spleen) by mature histiocytes, showing marked hemophagocytosis, was seen. PMID- 2266714 TI - [Family scapegoat, the delinquent adolescent]. PMID- 2266715 TI - [Aging]. PMID- 2266716 TI - [Assessment and classification of level of care of elderly patients]. PMID- 2266717 TI - [Assessment and management of agitated behavior in the elderly]. PMID- 2266718 TI - [Geriatric nurse practitioner's role in the United States and its implications to Korea]. PMID- 2266719 TI - [Case study on an anemic patient]. PMID- 2266721 TI - [Adjustment disorder of adolescence]. PMID- 2266720 TI - [A study to determine the effectiveness of Severance Hospice Home Care Program]. AB - The purpose of this study was to determine whether Severance Hospice Home Care Program was able to meet its objectives. This was done in order to show in detail the effects of hospice home care on the quality of life of terminally ill patients and to provide rationale for setting up more hospice home care programs in korea. The results of the study were as follows: The subjects of the study were 100 terminally ill patients who had died while in the hospice program and 64 family members who were registered with Severance Hospice Home Care Program between march 1988 and Feb. 1990. The nursing needs of these terminally ill patients were assessed by the nursing records of these patients. The need for pain control (82%) was the highest nursing need so far as the physical aspects were concerned. This was followed by poor appetite (37%), 8 dyspnea (34%), nausea and vomiting (30%) in that order of frequency. In regard to spiritual needs, the need for religious support was also high at 72%. Their main psychological symptoms were anxiety and fear (34%). Burn-out was a major problem for 44% of the family members. The psychological process experienced by the terminal ill patients was compared to the dying process, described by Kubler Ross. In comparison of the five stages outlined by kubler Ross with the dying process of the subjects it was found that the subjects not only experienced the five stages but also experienced denial and doubtfulness or denial with acceptance or acceptance with the expectation of a miracle. But rather than acceptance of the dying process, giving up was a frequent end point of the psychological process, of the subjects. However, when the combination of states was observed, most of the patients reached the state of acceptance in the dying process. It was difficult to identify a definite pattern of change in the psychological process of the subjects. Also it was difficult to identify the factors that influenced the psychological process. The symptoms of the terminally ill subjects just before dying, that is, 3-4 days before dying included apparent signs of dying. These were a reduction of intake (77%), reduction of the amount of urination (63%), increase in sleeping time (64%) and acceptance of dying by patients and their families who had been unaccepting before that time (66%). The primary care givers (family member's) degree of satisfaction with the care given to the patient by the hospice was 88.7%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266722 TI - [A study on the grief and coping pattern of mothers who have a chronically ill child]. AB - This study was done in order to identify symptoms of grief and patterns of coping in mothers of chronically ill children. Nurses, as health professionals, must understand helpful coping methods for mothers who have chronically ill children. Based on this knowledge, nurses can develop appropriate nursing intervention strategies, and so help the mothers to develop effective ways of coping and give support to mothers with chronically ill children in process of coping with this grief. The research questions guiding this research were: 1. what type of grief does the mother have at the time of child's diagnosis and at present? 2. what are the problems confronting the mother? 3. what are the coping patterns of the mother? 4. is there a difference according to child's diagnosis in the mother's grief and coping pattern? Ths subject for this study were obtained by taking a convenience sample of 120 mothers with a chronically ill child. Interviews took place in four medical school hospitals and one medical center in Seoul from March 19th to May 16th 1990. The tools used in this study were Mcfarlan's (1983), Grief contents, Folkman & Lazarus (1983), Ways of Coping and Hymovich's (1983) the Chronicity Impact and Coping Instrument. The findings were as follows; 1. Grief items had a maximum score of three points. The highest item scores at the time of diagnosis, were in order, heart broken, talkative, and could not do anything, at the present, 'talkative', 'heart broken' and 'busy myself with other things'. 2. The problems confronting the mothers were 'worry about ill child's future', 'her responsibilities in taking care of the ill child.' 3. Most of the mothers used similar ways of coping, that is 'problem focused coping', 'detachment', 'wishful thinking', 'seeking social support' and 'focusing on the positive and hardly any of them used 'tension reduction'. 4. There was a significant difference in coping methods according to the child's diagnosis, leukemia, cancer hemophillia and nephrotic syndrome. The most frequently used coping method was detachment, especially for the mother of the child with. 5. At the time of diagnosis there was a positive correlation between the level of grief and the coping method of detachment and seeking social support. PMID- 2266723 TI - [Informational operator-computer interactions under the effects of unfavorable environmental factors]. AB - This paper discusses changes in the psychic functions of an operator working in the interactive mode under the influence of adverse environmental effects that cannot be modified. It is postulated that in this situation the strategy of solving operational problems may transform due to changes in the structure of decision taking. The paper describes simulation of operator's activities involved in controlling information flows in a stressful environment of two degrees of complexity.The investigations demonstrated a trend for a decline of operator's work capacity, helped develop mathematical models to predict performance variations in an extreme environment, as well as formulate recommendations as to how computer-interaction efficiency can be increased. PMID- 2266724 TI - [Accommodation function of the eye in cosmonauts]. AB - The accommodation function was examined before and after flight by the method of ophthalmoergometry. During flight proximetric measurements were performed according to the routine method. Medical examinations of cosmonauts following short- and long-term flights demonstrated that the main visual functions remained adequate. The changes included the development of eye fatigue caused by visual load, complexity of visual tasks and unfavorable conditions of visual perception as well as decrease of the accommodation range, peripheral and central visual fatigue. These changes persisted during several days after flight. It is concluded that the crewmembers with an inadequate accommodation function should use methods of optic correction. The detection of the above changes indicates the necessity of prophylaxis of eye fatigue in order to maintain visual work capacity. PMID- 2266725 TI - [Pattern of vestibular reactions and sensory interactions in weightlessness (data of the experiment "Optokinesis")]. AB - This paper presents results of studying spontaneous and evoked optokinetic, opto oculomotor and vestibulo-oculomotor reactions in microgravity. The examinations were performed during the 7-day Soviet-Indian and 237-day Salyut-7 missions. During an early stage of adaptation to microgravity the following changes occurred: enhanced spontaneous activity of the eyes, including spontaneous nystagmus in one of the crewmembers, decline of the efficiency of saccadic pursuit (disappearance of saccades in the course of pursuit of a moving stimulus, decrease of the saccadic amplitude, emergence of correction microsaccades in response to fixation events), and decrease of the threshold of the optokinetic nystagmus. The compensatory counter-rotation of the eyeballs during head side-to side movements with open eyes in dark glasses did not disappear but slightly decreased, being slightly accompanied by low-amplitude nystagmus. When rocking the head with open eyes, one of the cosmonauts showed a complete eye destabilization and other cosmonauts displayed high-amplitude nystagmus. In response to head rotation with open eyes they developed clonic nystagmus. Vestibular stimulation in the form of active head movements helped to normalize the pattern of opto-ocular responses. PMID- 2266726 TI - [Physical performance and function of the cardiorespiratory system in additional respiratory resistance]. AB - This paper presents results of examining respiration and circulation parameters of healthy volunteers pedalling a bicycle ergometer at different degrees of inspiratory-expiratory resistance. In this situation the performance-limiting factor is an increased load on respiratory muscles. An additional signal of performance problems is respiratory discomfort. The paper gives a formula for predicting maximally allowable workloads in response to increased respiration resistance. PMID- 2266727 TI - [Specific individual characteristics of aviation specialists of small professional groups with different levels of psychological compatibility]. AB - Professional interaction of members of small groups of aviation operators was subject to psychophysiological analysis. Using the study of professional interaction of operators and the theory of operational mediation of personality relations, the major parameters characterizing psychological compatibility were determined. The practical application of these characteristics helped select small groups of aviation specialists, who differed largely in their psychological compatibility, compare them in terms of a great number of personality parameters, and define their various combinations. The list of variants presented may help better describe and predict psychological compatibility of members of small professional groups. PMID- 2266728 TI - [Physical and psychogenic effects of impact acceleration on the operator's functioning in the tracking system]. AB - It has been shown experimentally that simulated impact acceleration of 10 to 16 G may have a distinct psychogenic effect, which aggravates the action of the physical factor per se and, consequently, deteriorates the quality of operator's functions in the tracking system. Conversely, this exposure has a training effect and accelerates the development of adaptive and protective mechanisms which increase acceleration resistance of subjects, depending on their psychophysiological characteristics. PMID- 2266729 TI - [Review of main medical results of a one-year manned space mission on "Mir"]. AB - The objective of medical investigations during and after the 366-day manned mission was to accumulate information about human responses to long-term effects of microgravity. To do this, cardiovascular and other systems were examined in detail during and after exposure. The results gave evidence that the crewmembers well adapted to the long-term flight effects. Their good health condition and high work capacity were supported by adequate medical procedures. Postflight readaptation developed similarly to what was seen after previous flights of shorter duration (6-11 months). No qualitatively new changes in the physiological systems were detected during or after this mission. PMID- 2266730 TI - [Prognostication of man's health status in response to gravity-induced blood shifts based on continuous noninvasive measurement of arterial blood pressure using the Pen'iaz method]. AB - Exposure to +Gz acceleration, orthostatic tilt tests and LBNP tests causes distinct blood shifts and deterioration of cerebral circulation. In this case syncope episodes may be prevented by continuous monitoring of circulation parameters, specifically arterial pressure (AP). Our investigations have shown that continuous AP measurement by the Penjaz noninvasive technique may help earlier prediction of the health status in response to gravity-induced blood shifts. In this situation the development of a pre-collapse state is preceded by an emergence of distinct AP waves of the second-third order accompanied by a critical drop of pulse pressure. It is concluded that continuous AP measurement in the finger according to the Penjaz noninvasive technique holds promise as a medical monitoring method in a altered gravitational field. PMID- 2266731 TI - [Responses of human skeletal muscle fibers to a 370-day antiorthostatic hypokinesis associated with physical exercise]. AB - Gastrocnemius muscle biopsies of 10 healthy volunteers, aged 27 to 44 years, who were exposed to head-down tilt (-8 degrees) for 370 days, were examined. The test subjects were subdivided into two equal groups that were assigned exercises of different type and workload. This prolonged bed rest caused atrophic changes in skeletal myofibers and decrease of their metabolic rate. Regular exercise produced a beneficial effect on the myofibers and reversed hypokinesia-induced changes but partially. The efficacy of the countermeasures depended, to a certain extent, on the time, when they were initiated, and the intensity, with which they were performed: the efficacy was higher and atrophic changes were delayed, if the subjects began exercising earlier and did it more actively. PMID- 2266732 TI - [Changes in the ultrastructure of striated muscles and neuromuscular synapses of rats under the effects of a 13-day space flight]. AB - The ultrastructure of myofibers and neuromuscular synapses (NMS) of soleus, gastrocnemius and diaphragmatic muscles of rats flown on Cosmos biosatellite for 13 days was examined two days after landing. The myofibers showed atrophic and dystrophic changes that were different in various muscles: they were advanced in m. soleus, moderate in m. gastrocnemius and weak in the diaphragm. The greatest changes of NMS were seen in m. soleus, where the surface area of synaptic contacts decreased due to partial or total destruction of presynaptic structures. In m. gastrocnemius, structural changes in the synaptic apparatus included terminal sprouting. In the diaphragm, plastic changes of NMS were detected. It is stressed that electron microscopic changes in m. soleus reflect pathological shifts related to hemodynamic disorders that develop after landing. PMID- 2266734 TI - [Effects of increased doses of ultraviolet radiation on several parameters of human metabolism]. AB - Three experimental series, in which 20 test subjects took part, were carried out to investigate the effect of super-erythemic doses of ultraviolet irradiation on metabolic parameters. It was found that UV irradiation of 12-15% of the skin area led not only to skin changes but also to functional changes in certain organs and systems, which was indicated by variations of metabolic parameters. PMID- 2266735 TI - [State of the organ of vision and behavior of rats after action on the eye of increased doses of UV-irradiation]. AB - Male Wistar rats, weighing on the average 200 g, were used to investigate the clinical picture of photokerato-conjunctivitis and behavioral responses to the open field test after exposing their eyes to UV-radiation with an emission maximum at 302 nm. The development threshold for conjunctivitis was 0.6 kJ/m2 and that for keratitis was 0.8 kJ/m2. The corneal lesions such as perforation and formation of persistent (up to 60 days) changes emerged beginning with the dose 3 kJ/m2 (in 50% of animals). This dose is a minimally acting dose in terms of behavior. At the dose of 10 kJ/m2 the decrease of the horizontal motor activity, which was significant from day 14, became irreversible. Thus when the organ of vision is exposed to UV-radiation, it is important to take into consideration not only structural changes but also potential functional disorders, which are associated with enhancement of inhibitory processes in the CNS. PMID- 2266736 TI - [Photoelectric method of recording rotatory movement of human eyes]. PMID- 2266733 TI - [Histomorphometric analysis of the bones of rats exposed to "Cosmos-1887" space flight]. AB - Tibia and lumbar vertebrae of rats sacrificed 2 days after their 13-day space flight on Cosmos-1887 were examined histomorphometrically. It was found that the exposure led to osteoporosis of the primary and secondary spongiosa of tibia proximal metaphyses and early signs of bone reduction in the lumbar vertebrae spongiosa. The major cause of osteoporosis was inhibition of bone neoformation which was indicated by a lower number and activity of osteoblasts. A certain contribution was also made by enhanced bone resorption which was proven by a greater number of osteoclasts per bone volume and area unit in the tibia primary spongiosa. The fact that the rats were exposed to 1 G for 48 hours after landing resulted in readaptation developments, which were pointed to by a decrease of acid phosphatase in osteoclasts. PMID- 2266737 TI - [Mathematical substantiation of a sufficient number of measurements required for a reliable evaluation of parameters recorded in space biology and medicine]. PMID- 2266738 TI - [State of the pump function of the myocardium in monkeys after 7-day antiorthostatic hypokinesis]. PMID- 2266739 TI - [Personality characteristics determining making of risk-taking decisions]. PMID- 2266740 TI - Design and testing of external fixator bone screws. AB - In external fixation, bone screw loosening still presents a major clinical problem. For this study, the design factors influencing the mechanics of the bone screw interface were analysed and various experimental screws designed with the intention of maximizing the strength and stiffness of the inserted screw. Push in, pull-out and bending tests were then carried out on the three experimental screws, and on two commercially available screws in both a synthetic material and in cadaveric bone; photoelastic tests on different screw threadforms were also performed. The results of the push-in and pull-out tests indicate that both the screw threadform and cutting head have a significant effect on the holding strength of the screw. The photoelastic tests show that most of the applied load is distributed over the first few threads closest to the load, and that the area between the thread crests is subjected to high shear stresses. PMID- 2266741 TI - Detailed visualization of pulsatile flow fields produced by modelled arterial stenoses. AB - A multiple trace photochromic method was used to visualize the pulsatile flow field created by modelled arterial stenoses of 38% and 65% area reductions. Using flow parameters similar to those of a medium sized artery in man, the flow patterns at seven axial locations in relation to the stenosis were simultaneously photographed at various times throughout the flow cycle. With the 65% stenosis, the wall shear stress in the vicinity of the reattachment point was found to fluctuate quite strongly during the turbulent phase of the flow cycle, giving rise to instantaneous shear stresses that were at least eight times larger than those measured upstream. For the 38% stenosis, much smaller shear stresses were observed. These and other results are described in detail. PMID- 2266742 TI - Method for the design and analysis of a non-linear anisotropic lower limb prosthetic socket. AB - A simplified computer-based structural analysis procedure has been developed for evaluating the stresses in a lower limb prosthetic socket when subjected to external loads. This technique has been tested by studying a simple linear axisymmetric shell subjected to uniform loads. It was found that the stress and strain distribution obtained are close to those determined by a finite element technique. The method that has been proposed involves an incremental procedure, which can be used to analyse the behaviour of a prosthetic socket of irregular shape made from non-linear anisotropic materials. By employing the proposed procedure to study an example, in which a simplified lower limb prosthetic socket is subject to internal pressure and frictional forces, the effects of the material non-linearity have been found to be significant. PMID- 2266743 TI - Laser assessment of leaflet closing motion in prosthetic heart valves. AB - The dynamics of leaflet motion in heart valve prostheses (HVP), and in particular the closing velocity, is believed to be related to the valve sound and possibly to the phenomenon of valve cavitation. This paper describes a non-intrusive laser sweeping technique enabling the study of leaflet motion. The principle of measurement and the equipment involved are presented, together with the results of two commercially available, 29 mm bileaflet mitral valves, a St. Jude Medical, and an Edwards Duromedic valve. Experiments were carried out in a pulsatile mock flow testing loop designed to mimic physiological pressure waveforms and ventricular contraction. Measurements of heart rate were made in the range 70-120 beats min-1, with a ventricular pressure slope range of 1800-5600 mm Hgs-1 and a cardiac output range of 5.0-7.5 litres min-1. Motion analysis of the measured data focuses on the velocity of the leaflet immediately before closure. PMID- 2266744 TI - Performance of left ventricle based on pressure-volume relation. AB - The concept of body force (force per unit volume) is used to derive an expression for the radial force developed by the myocardium (active force) in a model of the left ventricle represented as an elastic thick-walled cylinder contracting symmetrically. This approach leads to a novel equation to describe the pressure volume relation in the Suga-Sagawa model. New indices to describe the mechanics of the left ventricular contraction are derived. Results tend to demonstrate that the radial active force generated by the myocardium will reach its peak value near end-systole, and that this peak is related to the peak isovolumic pressure. The study was carried out within a quasi-static approximation of the contraction (inertia forces neglected). PMID- 2266745 TI - Real-time tracking of parameters of lung mechanics: emphasis on algorithm tuning. AB - We consider the problem of tracking rapid changes in the viscous and elastic properties of the respiratory system by using mouth flow and transpulmonary pressure data measured during mechanical ventilation. A recursive least-squares algorithm with adjustable compensator is used for online estimation of an R-C model of the breathing mechanics. Specific simulation experiments are presented to provide guidelines to select suitable values for the key variable, which controls the compromise between tracking ability and noise sensitivity. The results obtained confirm the critical role of the optimum tuning in relation to the noise level. Experimental results obtained from data measured on mechanically ventilated dogs, in which respiratory distress syndrome was intravenously induced by oleic acid, demonstrate that the tuned algorithm is able to track appropriately both the viscous and elastic properties of lung mechanics. Parameter estimates are consistent with those obtained by standard and robust offline algorithms and their time course is in qualitative agreement with known physiopathological behaviour. PMID- 2266746 TI - Control and evaluation of high-frequency jet ventilation: mechanical lung model. AB - Ventilation systems that operate at high-frequency and deliver small volumes have the potential to provide adequate alveolar ventilation without excessive pulmonary pressures. One way of producing high-frequency ventilation is by use of jet bursts of an input gas through a cannula controlled by a solenoid valve. This high-frequency jet ventilation has yet to be quantitatively analysed for optimal clinical use. From an analysis of the jet-producing device, we obtained a quantitative relationship which allowed us to predict the gas volume of a jet burst (Vjet) from the driving pressure (Pd), and the jet duration (tI). The device was applied to a mechanical lung model (a tube attached to an elastic bag corresponding to the lung airway and alveolar space). We examined how the control variables of the jet ventilation system changed the bag (alveolar) volume with respect to Vjet, the volume of entrained gas, and the volume of shunted gas. Using a nitrogen washout analysis, we evaluated the operating lung volume, effective dead-space volume (Veds), and effective ventilation rate (Veff). We found that Veds is independent of the individual effects of jet cycle frequency, duty cycle, cannula diameter, and entrainment fraction. While Veds was not affected significantly by the shape of the airway, it did depend on the distance of the jet cannula tip to the ventilated bag (or alveolar region) and on the tidal volume. PMID- 2266747 TI - Comparison and testing of least-squares time domain inverse solutions in electrocardiography. AB - The use of several mathematical methods for estimating epicardial ECG potentials from arrays of body surface potentials has been reported in the literature; most of these methods are based on least-squares reconstruction principles and operate in the time-space domain. In this paper we introduce a general Bayesian maximum a posteriori (MAP) framework for time domain inverse solutions in the presence of noise. The two most popular previously applied least-squares methods, constrained (regularized) least-squares and low-rank approximation through the singular value decomposition, are placed in this framework, each of them requiring the a priori knowledge of a 'regularization parameter', which defines the degree of smoothing to be applied to the inversion. Results of simulations using these two methods are presented; they compare the ability of each method to reconstruct epicardial potentials. We used the geometric configuration of the torso and internal organs of an individual subject as reconstructed from CT scans. The accuracy of each method at each epicardial location was tested as a function of measurement noise, the size and shape of the subarray of torso sensors, and the regularization parameter. We paid particular attention to an assessment of the potential of these methods for clinical use by testing the effect of using compact, small-size subarrays of torso potentials while maintaining a high degree of resolution on the epicardium. PMID- 2266748 TI - Device for measuring soft tissue interface pressures. AB - This paper describes the construction and performance of a simple pressure sensing device with a continuous electrical output. It was constructed utilizing a commercially available transducer, an electropneumatic sensor capsule and a 1 m long tube. The transducer used was a piezo-resistive pressure-sensitive device producing an output voltage proportional to the applied pressure. This low cost, high accuracy device is temperature compensated and shows good linearity and negligible hysteresis. The sensor cell has a good thickness-to-diameter ratio and is sufficiently flexible to conform to most contours of the body. The tubing that conveys the pressure transmitting fluid also serves as a means of keeping the transducer distant from the measuring site. The device showed a highly satisfactory performance under laboratory conditions and has proven to be robust and reliable when used for clinical studies. PMID- 2266749 TI - Compartmental mean residence time in a mammillary model with an effect compartment after intravenous or oral administration. AB - A general estimation of mean residence time (MRT) in an effect compartment E, associated with a linear mammillary n-compartment model is presented: elimination takes place from the central and the effect compartments. Even though no sample is available from E, the MRT of the drug in this compartment can be estimated after intravenous or oral administration. Furthermore, the effect of MRT is independent of the route of administration. Also, with no new calculation, the method provides the area under the amount-time curve in compartment E. PMID- 2266750 TI - A flexible FFT algorithm for processing biomedical signals using a personal computer. AB - The aim was to demonstrate the possibility of using personal computer PC-DOS (or generally MS-DOS) for real-time (or quasi real-time) biomedical signal processing by adding a simple A/D conversion card and the mathematical coprocessor XXX87. We have realized an assembly written fast Fourier transform (FFT) routine derived from a radix-4 algorithm, which is autogenerated, i.e. an algorithm modified by another algorithm running off-line according to the number of FFT points. The program is implemented as a subroutine to be called upon by high-level language in different procedures. This approach reduces the computational time, which is particularly useful when many Fourier transforms on different data arrays are required. Reported here are two different applications of the routine as applied to the spectral analysis of Doppler ultrasound velocimetry and surface electromyography. PMID- 2266751 TI - Fast sinc interpolation of digitized signals using the Hilbert transform. AB - Sinc interpolation is a useful method for improving digital waveforms measured by A/D converters. This algorithm reconstructs the intermediate points between sampled data. I describe here a fast method for computing the sinc interpolation by the use of the Hilbert transform. PMID- 2266752 TI - Haemodynamic approach to reducing thrombosis and haemolysis in an impeller pump. AB - In the experimental and clinical support of the failing heart, the impeller-type centrifugal pumps continue to be of interest because of their inherent advantages; however, the blood compatibility of these pumps still remains to be improved. From the viewpoint of haemodynamics, thrombosis and haemolysis could be reduced by eliminating the stagnation and turbulence of blood flow within the pump, which frequently takes place near the blood contracting surfaces of the pump, when the impeller contours do not coincide with the stream surfaces of the blood. It is suggested that it could be advantageous to design impeller contours according to the stream surfaces, by solving the partial differential equations of continuity, motion and energy. An impeller shroud and vane based on this approach would be fully rinsed by non-turbulent flow and there would then be neither stagnation nor turbulence within the pump, with the result that thrombosis and haemolysis could be reduced. A new impeller pump, developed according to this method, was evaluated as a left ventricular device in four dogs. The bypass flow was controlled at 40-50% of the total flow, each test lasting 6 h. All of the haematological parameters, measured every 2 h, remained within normal range. There was no thrombosis, and coagulation in the pump was avoided by a small dose of heparin to maintain the activated coagulation time (ACT) under 200" in the experiments. PMID- 2266753 TI - Effect of exercise conditioning on red blood cell volume and erythropoietin concentration in the beagle dog. AB - To determine if endurance conditioning has a stimulating effect on red blood cell and erythropoietin production, we exercised five beagle dogs on a motor-driven treadmill for 1 hour per day, 5 days per week, for 6 weeks at a speed near their maximal capability. Three additional beagles were kept in cages and served as nonconditioned controls. Endurance conditioning in these dogs produced no increase in red blood cell mass, serum erythropoietin concentration, or any other blood cell index measured. We conclude that this type of exercise conditioning does not produce the necessary stimulus for an increase in erythropoiesis. PMID- 2266754 TI - The effect of training on the norepinephrine response at rest and during exercise in 5 degrees and 20 degrees C environments. AB - Eleven males were examined at rest and during submaximal exercise in 5 degrees C and 20 degrees C environments to determine if the norepinephrine (NE) and other physiological responses in the cold would be altered by eight weeks of training. Blood samples were obtained at the end of 15 minutes of rest and submaximal exercise, and were assayed for NE. Pretraining resting NE levels in the 5 degrees C condition were significantly higher than those found in the 20 degrees C environment (684 +/- 89 vs 491 +/- 48 pg/ml). A significant training effect reduced resting NE levels in the 5 degrees C (502 +/- 77 pg/ml) but not the 20 degrees C (392 +/- 45 pg/ml) condition. Pre and posttraining exercise NE levels were elevated above resting in both the 5 degrees C (1477 +/- 136 vs 1559 +/- 208) and the 20 degrees C environments (1623 +/- 176 pg/ml vs 1444 +/- 224 pg/ml), but were not significantly different between conditions. Skin temperatures were significantly lower, and resting blood pressure was significantly higher in the 5 degrees C condition. These data suggest that both cold and exercise act as stimulators of NE release, but an additive effect on NE of cold and exercise does not occur. The resting NE levels pre and posttraining in the 5 degrees C condition suggest that a cross tolerance to cold stress was present. PMID- 2266755 TI - The effect of exercise intensity on serum lipoprotein responses. AB - The purpose of this study was to determine the effect of exercise intensity on lipoprotein responses. Eleven normolipidemic male volunteers (X +/- SD = 23.1 +/- 2.4) participated in the study. The subjects were assessed for VO2max and ventilatory threshold (VT), matched for VO2max and then randomly assigned to one of two groups: Group A, which exercised for 12 minutes at an intensity 15% below VT (n = 5), and Group B, which exercised for 12 minutes at an intensity 15% above VT (n = 6). The lipoprotein measures HDL-C, LDL-C, total cholesterol (TC), and triglycerides (TG) were assessed from blood samples taken pre-exercise and immediately post-exercise as well as one, 24, and 48 hours post-exercise. A 2 X 5 split plot ANCOVA (controlling for pre-exercise values), revealed no significant differences between groups for HDL-C, TC or LDL-C. However, when means were collapsed across groups, TC levels measured immediately post-exercise were significantly higher than those taken 24 and 48 hours post-exercise (168.0, 159.1, and 159.9 mg.dl-1, respectively; p less than 0.05). A significant interaction was found for the TG measurements. For Group A, TG levels were elevated immediately post-exercise, but decreased significantly at the 1 and 24 hours post-exercise sampling, before returning to baseline levels at the 48 hour post-exercise measurement (93.2 +/- 3.1, 69.5 +/- 4.2, 66.8 +/- 6.7 and 99.5 +/- 2.1 mg.dl-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266756 TI - Hepatic antipyrine metabolism in athletes. AB - The aim of the present study was to investigate the influence of prolonged physical exercise on hepatic metabolism. An oral antipyrine loading test (15 mg/kg body weight) was carried out on 24 healthy male subjects: 8 controls, 8 sprinters (anaerobic activity), 8 long distance runners (aerobic activity). Antipyrine clearance resulted to be significantly higher in athletes vs. controls, without a significant difference between the two groups of athletes. These results put forward the importance of the degree of physical activity (1) for the evaluation of antipyrine-loading-test results as expression of liver function and (2) whenever drugs with a low therapeutic index are used in athletes. PMID- 2266757 TI - Physiological adjustments of facial cooling during exercise. AB - Physiological and metabolic output responses to facial cooling during a graded maximal exercise and a prolonged submaximal exercise lasting 30 min at 65% VO2 max were investigated in five male subjects. Pedalling on a cycle ergometer was performed both with and without facial cooling (10 degrees C, 4.6 M.S-1). Facial cooling at the end of greated maximal exercise apparently had no effect on plasma lactate (LA), maximal oxygen consumption (VO2 max), maximal heart rate (HR max), rectal temperature (Tre), work load, lactate threshold (LT), ventilatory threshold (VT) and onset of blood lactate accumulation (OBLA). However, the response to facial cooling after prolonged submaximal exercise is significantly different for heart rate and work load. The results suggest that facial wind stimulation during maximal exercise does not produce a stress high enough to alter the metabolic and physiological responses. PMID- 2266758 TI - The effect of training specificity on maximal and submaximal physiological responses to treadmill and cycle ergometry. AB - The purpose of this study was to investigate the effect of training specificity during maximal and submaximal treadmill (TM) and bicycle ergometer (BE) exercise. A group of trained runners (RG, no. 7) and trained bikers (BG, no. 7) underwent graded exercise testing on both TM and BE, utilizing the same testing protocol within each exercise mode for both groups. Data for VO2 HR and BP were collected during each 3 min stage. Group by trial ANOVAs followed by Tukey's post hoc analysis, showed no group difference in VO2max, HRmax or BPmax during TM exercise. However, during each of the first four submaximal 3 min stages, VO2 and HR were significantly less (p less than .05) in RG vs BC, with no significant difference in BP. During BE exercise, VO2max was significantly less for both groups compared with TM (RG-59.6 vs 50.1 ml.kg-1.min-1 BS-59.4 vs 55.1 ml.kg 1.min-1) (p less than .05), with BG exhibiting the greater BEmax (p less than .05). RG also had a reduced HRmax during BE exercise (p less than .05). Both groups showed greater BPmax during BE vs TM exercise (p less than .05). Although submaximal VO2 was slightly less during BE for each stage in RG than BG, these differences were not significant as measured either by ml.kg-1.min-1 or l.min-1. Both submaximal HR and BP mirrored the VO2 response, with no significant differences between RG and BG. These data agree with previous studies, showing a greater effect of training specificity during maximal BE than during maximal TM exercise. However, during submaximal exercise, training specificity appear to have a greater effect during TM than BE exercise. PMID- 2266759 TI - An on-site test battery to evaluate giant slalom skiing performance. AB - The purpose of this study was to determine if an on-site test battery would distinguish among three levels of giant slalom skiing ability. The test battery consisted of a 20-m shuttle run test, Wingate 60s cycling test, hexagonal obstacle test, high box test, double leg jumping test and vertical jump test. These tests were selected since previous studies have identified aerobic endurance, anaerobic endurance, power and agility as important components for Alpine skiers. Both construct validity and criterion related validity of the test battery were examined using data from 11 club skiers, 14 divisional level skiers, and 9 provincial level skiers. To establish construct validity, univariate F tests examined differences among the three levels of skiers. Significant (P less than 0.05) differences were found between the club skiers and the better skiers (divisional and provincial level) for the following test variables: peak power, mean power, and post-exercise lactate for a 60s Wingate cycle ergometer test, high box test, hexagonal obstacle test, double leg jumping test, and shuttle run test. Criterion related validity was established since there were significant correlations between giant slalom performance time and the hexagonal obstacle test (r = 0.82), high box test (r = -0.80), and double leg jumping (r = -0.86). These data illustrate that an on-site test battery can be used to distinguish among giant slalom Alpine skiers. PMID- 2266760 TI - Running addiction: measurement and associated psychological characteristics. AB - Runners frequently become addicted to running and continue to run even when it is detrimental to their health. In the present study a paper and pencil test to measure running addiction, the running addiction scale (RAS) was constructed and evaluated and used to investigate the psychological correlates of running addiction. The RAS, symptom check list, locus of control scale, commitment to running scale (CR), and a questionnaire about the individual's running habits and degree of addiction were administered to 32 male and 15 female runners. The results suggest that the RAS is reliable and valid, correlating with self-rated addiction. The CR score was correlated with self-rated addiction for males but not for females suggesting that the RAS and CR measure different characteristics and that for female runners commitment to running can occur without addiction. Large gender differences were found in the correlations between the RAS, CR, run frequency, and run duration with the personality, mood, and locus of control scores. Running addiction was found to be associated with high frequency of running and with positive personality characteristics but not with mood enhancement, while the duration of running was found to be associated with mood enhancement. These results suggest that the benefits of running to mood may be obtained without addiction. PMID- 2266761 TI - Suppression of cerebral evoked potentials preceding rapid reaction movement. AB - In this study we examined the gating of the cerebral evoked potentials during warning-imperative stimulus intervals and preceding the rapid movement. We also examined the possibility of the gating phenomenon occurring in the precentral cortex. The experiment showed that the amplitudes of cerebral evoked potentials increase at all C3 and CZ during the warning-imperative stimulus intervals. Therefore, it seems that gating does not occur within the central nervous system during warning-imperative stimulus intervals. Furthermore, we observed that preceding rapid movement, the amplitudes of the cerebral evoked potentials decreased at all C3 and CZ. In the present experiment, it does not seem that a peripheral mechanism plays a role in the rapid movement. Therefore, it can be concluded that the decrease in amplitude of the cerebral evoked potentials preceding rapid movement may be due to a central mechanism irrespective of afferent information. In addition, we confirmed that the amplitude of cerebral evoked potentials decreases considerably at the precentral cortex and that the attenuation in amplitude of cerebral evoked potentials is more pronounced over the CZ than over the C3. PMID- 2266762 TI - Meniscal trauma (of the knee) and surgical intervention. A review of literature. AB - Through extensive reviews of literature, the semi-lunar cartilaginous discs (located within the tibiofemoral joint) will be examined with regard to their make-up, function, and response to trauma. Methods of diagnosing meniscal injury will be explored, as will past and present surgical procedures. An outlook into future methods of treating meniscal lesions will be touched upon. PMID- 2266763 TI - A survey of running injuries in 1505 competitive and recreational runners. AB - A 33 item multiple choice questionnaire was circulated; completed questionnaires from 1505 runners (1130 male and 375 female) were obtained. Questions focused upon training, injuries sustained, and medical care. Biomechanical imbalances such as leg length inequality appear to be a major contributing factor to running injuries. Correction of an underlying biomechanical defect may be important in the treatment of many running injuries. Female runners were found to be more susceptible than males to stress fractures at higher mileages. The cause of this increased incidence may be attributable to lower bone mineral density levels as a result of hormonal factors. Factors such as running surface, age and stretching techniques do not appear to play a significant part in the pathogenesis of running injuries. PMID- 2266764 TI - Infectious episodes in runners before and after the Los Angeles Marathon. AB - An epidemiologic study of Los Angeles Marathon (LAM) applicants was conducted to investigate the relationship between self-reported infectious episodes (IE), training data, and LAM participation. Eight days before the LAM, 4926 of 12,200 applicants were randomly selected, and sent a pilot-tested four page questionnaire, which was received 7 days after the LAM. The 2311 respondents were found to be 2.0 yr older and 7.6 min faster than other LAM finishers (p less than .01). Univariate and multivariate analyses (logistic regression) were conducted to test the relationship between IE and km/wk of running (6 total categories). The final model tested controlled for age, marital status, reported sickness in other members of the runner's home, perceived feelings of stress in response to personal training regimens, and the suppressive effect of sickness on regular training. In runners training greater than or equal to 97 vs less than 32 km/wk, the odds ratio (OR) for IE during the 2 month period prior to the LAM was 2.0 (95% confidence interval (CI) 1.2-3.4). A test for trend showed an increase in OR with increase in km/wk category (p = .04) which was largely explained by the increased odds of reported sickness in the greater than or equal to 97 km/wk category. Of the 1828 LAM participants without IE before the LAM, 236 (12.9%) reported IE during the week following the LAM vs 3 of 134 (2.2%) similarly experienced runners who did not participate, OR = 5.9 (95% CI 1.9-18.8). These data suggest that runners may experience increased odds for IE during heavy training or following a marathon race. PMID- 2266765 TI - Exercise-induced purpura. AB - A 11-year-old boy developed purpura on the back and chest on more than 5 occasions following vigorous exercise. This eruption should be added to the list of differential diagnosis of the dermatosis experienced by athletes. PMID- 2266766 TI - The coexistence of Osgood-Schlatter's disease with Sinding-Larsen-Johansson's disease. Case report in an adolescent soccer player. AB - Osgood-Schlatter's disease and Sinding-Larsen-Johansson's diseases belong to the group of osteochondroses which is composed of disorders related to trauma or abnormal stress without evidence of osteonecrosis. They both affect adolescents more frequently when there is a history of participation in sport and their pathogenesis is related to a traumatically induced disruption that shows more easily when a rapid growth spurt is present. The coexistence of these two diseases in a young soccer player is reported. In this case the bone mineral content of every athlete of the team was determined and the bone density of the injured boy resulted lower the mean values of the group. The result suggests the possibility that transitory osteoporosis, connected with the rapid growth spurt that is typical in the adolescence, should be considered as one of the possible causes which contribute to the development of osteochondritic lesions. PMID- 2266767 TI - For the health of it. Pain in the neck: Part I. PMID- 2266768 TI - Charcot and the idea of hysteria in the male: gender, mental science, and medical diagnosis in late nineteenth-century France. PMID- 2266769 TI - Lessons in medical politics: Thomas Wakley and the Irish Medical Charities, 1827 39. PMID- 2266770 TI - Plague in Elizabethan and Stuart London: the Dutch response. PMID- 2266771 TI - Phylogenetic distribution of superoxide dismutase supports an endosymbiotic origin for chloroplasts and mitochondria. AB - Three isozymes of superoxide dismutase (SOD) have been identified and characterized. The iron and manganese isozymes (Fe-SOD and Mn-SOD, respectively) show extensive primary sequence and structural homology, suggesting a common evolutionary ancestor. In contrast, the copper/zinc isozyme (CuZn-SOD) shows no homology with Fe-SOD or Mn-SOD, suggesting an independent origin for this enzyme. The three isozymes are unequally distributed throughout the biological kingdoms and are located in different subcellular compartments. Obligate anaerobes and aerobic diazotrophs contain Fe-SOD exclusively. Facultative aerobes contain either Fe-SOD or Mn-SOD or both. Fe-SOD is found in the cytosol of cyanobacteria while the thylakoid membranes of these organisms contain a tightly bound Mn-SOD. Similarly, most eukaryotic algae contain Fe-SOD in the chloroplast stroma and Mn SOD bound to the thylakoids. Most higher plants contain a cytosol-specific and a chloroplast-specific CuZn-SOD, and possibly a thylakoid-bound Mn-SOD as well. Plants also contain Mn-SOD in their mitochondria. Likewise, animals and fungi contain a cytosolic CuZn-SOD and a mitochondrial Mn-SOD. The Mn-SOD found in the mitochondria of eukaryotes shows strong homology to the prokaryotic form of the enzyme. Taken together, the phylogenetic distribution and subcellular localization of the SOD isozymes provide strong support for the hypothesis that the chloroplasts and mitochondria of eukaryotic cells arose from prokaryotic endosymbionts. PMID- 2266772 TI - Pharmacokinetics of growth hormone secretion in humans induced by growth hormone releasing hormone. AB - This investigation compares the age- and sex-related changes in growth hormone (GH) response to growth hormone releasing hormone (GHRH) in normal subjects using an appropriate pharmacokinetic model. Twenty-five subjects (14 males and 11 females) aged 23-89 yr received a single intravenous bolus dose (1 microgram/kg) of GHRH-40 solution. Plasma GH concentration-time profiles are best characterized by a biexponential equation (or one-compartment model) with first-order release and disappearance rates and an equilibration lag time. The harmonic mean release rate half-life is similar for both sexes (males: 12.6 min vs. females; 11.4 min) but significantly different across age groups (23-35 yr: 7.2 min vs. 50-89 yr: 16.8 min). The mean disappearance rate half-life and GHRH-equilibration time lag for females (33.6 and 20.4 min, respectively) and the higher age group subjects (32.4 and 21.6 min, respectively) are significantly longer than those of males (22.8 and 9 min, respectively) and the lower age-group subjects (21.6 and 8.4 min, respectively). The mean metabolic clearance rate of GH is significantly lower (p less than 0.02) for females than for males (3.1 vs. 4.83 ml/hr.m2). However, the production rate and the amount of GH released by the pituitary for our subjects appear to be very similar for both males (8.7 micrograms/hr.m2 and 4.65 micrograms/m2) and females (9.33 micrograms/hr.m2 and 5.11 micrograms/m2). PMID- 2266773 TI - Prolonged changes in plasma concentrations of catecholamine metabolites following a single infusion of an MPTP analog. AB - The magnitude and duration of effects of a single intravenous injection of 4' amino MPTP, an analogue of the dopamine neurotoxin, MPTP, on plasma levels of catechols and normetanephrine were examined in conscious dogs. Plasma samples were collected prior to treatment with intravenous saline or 4'-amino MPTP.2HCl (22.5 mg/kg) and at weekly intervals for six weeks following treatment. Saline treatment had no effect on plasma levels of any of the measured compounds. Following 4'-amino MPTP, plasma DHPG fell to 14% of the pre-injection value and remained decreased for the full 6-week test period, with partial recovery by week 6 to 42% of the pre-injection value. Plasma DOPAC levels fell to 28% of pre injection values 1 week after treatment with 4'-amino MPTP and showed no evidence of recovery during the 6-week test period. Plasma DOPA fell to 58% of the pre injection level, while concentrations of the catecholamines NE, EPI, and DA were generally unaffected. The plasma concentration of the O-methylated NE metabolite, normetanephrine, was also unchanged by 4'-amino MPTP treatment. There were no differences in the concentrations of DA, NE or EPI within the adrenal medulla between saline and 4'-amino MPTP treated groups. This pattern of changes in plasma levels of catechols, which is consistent with presynaptic inhibition of MAO within sympathetic terminals, may be a useful indicator of exposure to MPTP like neurotoxins. PMID- 2266774 TI - Disproportional release of differently glycosylated forms of human renin by furosemide. AB - Concanavalin A (con A) chromatography of human plasma revealed the presence of three differently glycosylated forms of active renin(AR) and prorenin(PR), including the con A unbound forms(AR-I and PR-I), the loosely-bound forms (AR-II and PR-II), and the tightly-bound forms (AR-III and PR-III). These three forms of AR and PR were observed in human renal extracts. Normal male volunteers were intravenously given the diuretic furosemide (20 mg), kept standing for one hr and the effect on each form of renin was examined. These treatments elevated the plasma concentrations of AR-I, II and III by 2.1 +/- 0.2, 2.6 +/- 0.5, and 6.3 +/ 1.1-fold, respectively (n = 12), thereby indicating that the increase in AR-III was significantly larger than that in the other two forms (P less than 0.01). This disproportional increase was accompanied by a significant increase in the relative percent of AR-III in plasma from 21.6 +/- 2.5 to 42.2 +/- 3.0% (P less than 0.01). On the other hand, increase in the plasma levels of PR-I, II, and III was small (1.4 +/- 0.1, 1.0 +/- 0.1, and 1.1 +/- 0.2-fold, respectively). These results provide evidence for the presence of differently glycosylated forms of AR and PR in human plasma and suggest the preferential release of AR-III with the acute stimulation of renin, by furosemide. PMID- 2266775 TI - Estrogen-androgen antagonism in the regulation of epidermal growth factor in mouse submandibular salivary gland and kidneys. AB - To eludicate hormonal regulation of epidermal growth factor (EGF) concentration we studied the effects in adult female mice of ovariectomy and postovariectomy treatments with testosterone plus estradiol on the EGF concentrations in submandibular salivary gland (SMG), plasma, kidneys and urine. In the tissues, we also studied the location of EGF immunohistochemically and measured EGF mRNA. After ovariectomy, SMG EGF first decreased to one third of preovariectomy level. After postovariectomy day 10 it started to increase and reached by day 80 3.5 fold the preovariectomy level. Simultaneously, EGF mRNA increased. Testosterone treatment further strongly augmented the levels of both EGF mRNA and EGF. A small dose of estradiol counteracted slightly the mRNA effect of testosterone. After ovariectomy plasma EGF first increased 1.3-fold by day 10, then returned to the initial levels, and rose again 1.6-fold by day 80. Testosterone treatment induced a further 1.5-fold increase. Estradiol did not counteract this effect. Kidney EGF decreased 15% by postovariectomy day 20. This was preceded by a decrease in EGF mRNA from day 10 onwards. The EGF concentration recovered during the 80 days, but the EGF mRNA level stayed low. Testosterone treatment further reduced the levels of both EGF mRNA and EGF. This effect was counteracted by estradiol. Urine EGF increased after ovariectomy to a peak (1.7-fold) by day 40. It then returned to the preovariectomy levels by day 80. Testosterone treatment increased urinary EGF 1.9-fold; concomitant estradiol had no effect. PMID- 2266776 TI - Effect of a new synthetic free radical scavenger, 2-octadecyl ascorbic acid, on the mortality in mouse endotoxemia. AB - Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. In order to clarify the role of oxygen radicals in endotoxemia, we measured the serial lipid peroxide changes resulting from systemic radical reactions using a newly developed colormetric method. To determine the effect of a free radical scavenger on mortality in endotoxemia, a new synthetic scavenger, 2-Octadecylascorbic acid (CV-3611), which overcome the detrimental properties (circulation half-life and cell penetration) of native SOD, was used in the model of mouse endotoxemia induced by the i.p. administration of E-coli endotoxin (10 mg/kg). Serial LPO (Lipid Peroxide) changes revealed significant elevations from the basal level of 4.52 +/- 0.79 nmol/ml to 10.5 +/- 2.04 nmol/ml at 2h (P less than 0.05), 12.0 +/- 2.44 nmol/ml at 8h (P less than 0.05), 32.8 +/- 12.5 nmol/ml at 12h (P less than 0.05) and 13.6 +/- 2.40 nmol/ml at 24h (P less than 0.05) following i.p. administration of E-coli. The circulation half life of CV-3611 was checked by a reversed-phase HPLC after 10 mg/kg s.c. administration. The level of CV-3611 reached peak levels of 0.54 +/- 0.10 micrograms/ml at 1h and 0.52 +/- 0.20 micrograms/ml at 2h then gradually decreased to the level of 0.04 +/- 0.004 micrograms/ml at 6h and to a non-detectable level at 24h after s.c. administration. Increased survival was seen at 2 days (P less than 0.001) after E-coli endotoxin administration in the CV-3611 treated group compared to the control group. These results suggest that oxygen derived free radicals contribute to mortality in mouse endotoxemia and that antioxidants such as CV-3611 may provide a new therapeutic avenue by improving survival of patients with gram-negative bacterial sepsis. PMID- 2266777 TI - A model to study physiological activation of phospholipase A2 and vasorelaxation by lysophosphatidylcholine. AB - Earlier we demonstrated that micellar solutions of LPC caused endothelium dependent relaxation of rabbit thoracic aorta and bovine intrapulmonary artery and vein through a cyclic GMP-dependent mechanism. The availability of LPC for vasorelaxation depends on its production by deacylation of PC by PLA2. We assessed the possible activation of PLA2 by commonly used vasorelaxants such as acetylcholine, bradykinin, calcium ionophore A23187 and thrombin and vasoconstrictors like histamine and phenylephrine in the presence of indomethacin in a model system where 14C PC was incorporated into bovine intrapulmonary arterial segments. Taking the ratio of 14C PC:LPC formed by exogenous PLA2 as an index of deacylation, we found that while all the agents relaxed the strips in an endothelium-dependent manner, only thrombin caused relaxation followed by an increase in 14C LPC and a concomittant decrease in 14C PC indicating activation of PLA2. Our data show that PC/PLA2 system can be activated to generate LPC for vascular relaxation under specific physiological conditions. This model system can be used to monitor PLA2 activity and LPC production to compensate flow and pressure induced changes in arteries. PMID- 2266778 TI - The effect of cholinergic manipulations on the analgesic response to cobrotoxin in mice. AB - Intracerebroventricular (i.c.v.) injection of cobrotoxin (CT), a neurotoxin isolated from the venom of Naja naja atra, produced an antinociceptive response in mice as measured by the tail-flick test. This effect of CT was blocked by systemic administration of atropine, but not by methylatropine or naloxone. Depletion of central acetylcholine (ACh) by hemicholinium-3 (HC-3) blocked the antinociceptive action of cobrotoxin. These results suggest that central cholinergic neurons are important for the mediation of the antinociceptive properties of cobrotoxin. PMID- 2266779 TI - Mouse brain distribution of a carbon-11 labeled vesamicol derivative: presynaptic marker of cholinergic neurons. AB - The regional mouse brain distribution of a new carbon-11 labeled derivative of vesamicol, [11C]-5-(N-methylamino)benzovesamicol [( 11C]MABV) is reported. Radiotracer concentrations in vivo are in the rank order of striatum greater than cortex greater than hippocampus greater than hypothalamus greater than cerebellum, consistent with reported distributions of other presynaptic cholinergic neuronal markers. In time course studies, striatum/cerebellum and cortex/cerebellum ratios for (-)-[11C]MABV continue to increase to values of 13 and 5, respectively, 75 min after i.v. injection of [11C]MABV. The specific binding in striatum and cortex is lowered by pretreatment with (+/-)-vesamicol, and shows stereoselectivity with lower uptake and lower ratios for the (+) enantiomer. (-)-enantiomer. (-)-[11C]MABV is proposed as a positron-emitting radioligand for the in vivo study of presynaptic cholinergic neurons. PMID- 2266780 TI - Lack of biological activity of preproendothelin [110-130] in several endothelin assays. AB - A 21 amino acid peptide containing the prepropendothelin sequence from amino acids 110 to 130 and two intrachain disulfide bonds was synthesized and tested for biological activity in the following endothelin assays: 1.) a competition binding assay using [125I]ET-1 and dog heart membranes, 2.) three RIA's using 125I-ET-1, -2 and -3 and the respective anti-ET rabbit antisera; and 3.) a contractile activity bioassay using hamster aortic rings. The synthetic peptide which has been referred to as the "endothelin-like" peptide occurs 36 amino acids C-terminal to endothelin in the prepro-protein sequence. It contains only 40% sequence homology to the three endothelin isoforms, but has the same sequence and cyclization pattern of cysteines at positions 1, 3, 11 and 15. Despite the overall similarity in secondary structure to the three isoforms of endothelin and sarafotoxin S6b, preproendothelin [110-130] had no activity in any of the assays when tested at concentrations of 10(-10)M to 10(-5)M. PMID- 2266781 TI - Interleukin-1 stimulates catecholamine release from the hypothalamus. AB - During a 60-min period, the in vitro release of norepinephrine (NE) from the hypothalami of male rats decreased by 28%. The presence of 50 or 100 ng of interleukin 1-beta (IL-1 beta) in the incubation medium prevented this decrease and raised the release by 17% or 45% respectively (P less than 0.05). The average release of dopamine (DA) decreased by 55% in the control group but 50 ng of IL-1 beta cut this decrease to 25%, and 100 ng of IL-1 beta not only completely prevented the decrease but raised the release by 44% (P less than 0.05). In a following 60-min period, when the hypothalami from the treatment groups were incubated without IL-1 beta, it resulted in sharp declines in the release of NE and DA, confirming that IL-1 beta was the stimulus for the increases in catecholamine release in the previous incubation period. It is concluded that IL 1 beta stimulates the release of catecholamines (and probably other neurotransmitters) in the brain which, in turn, mediate its central and neuroendocrine actions. PMID- 2266782 TI - Effect of desipramine on dopamine receptor binding in vivo. AB - Effect of desipramine (given i.p. 30 min prior to the tracer injection) on the in vivo binding of 3H-SCH23390 and 3H-N-methylspiperone (3H-NMSP) in mouse striatum was studied. The ratio of radioactivity in the striatum to that in the cerebellum at 15 min after i.v. injection of 3H-SCH23390 or 45 min after injection of 3H NMSP were used as indices of dopamine D1 or D2 receptor binding in vivo, respectively. In vivo binding of D1 and D2 receptors was decreased in a dose dependent manner by acute treatment with desipramine (DMI). A saturation experiment suggested that the DMI-induced reduction in the binding was mainly due to the decrease in the affinity of both receptors. No direct interactions between the dopamine receptors and DMI were observed in vitro by the addition of 1 mM of DMI into striatal homogenate. Other antidepressants such as imipramine, clomipramine, maprotiline and mianserin also decreased the binding of dopamine D1 and D2 receptors. The results indicated an important role of dopamine receptors in the pharmacological effect of antidepressants. PMID- 2266783 TI - A more sensitive and specific radioenzymatic assay for catecholamines. AB - This modification of the catechol-O-methyltransferase (COMT) based radioenzymatic assay for norepinephrine (NE) and epinephrine (E) improves sensitivity, selectivity and eliminates many inhibitors of COMT. Prior to assay, samples are extracted into heptane with diphenylborate, then into dilute acetic acid. This extraction procedure has an efficiency of 78% for NE but less than 2% for S adenosylmethionine (SAM). The extraction procedure also excludes calcium and other COMT inhibitors present in urine, plasma and every tissue tested. This eliminates the requirement for individual standardization of tissue and urine samples. Sensitivity of the assay for NE and E is 10 and 6 pg/ml respectively in 1 ml of plasma. The intraassay coefficients of variation for NE and E are 4 and 13% and the interassay coefficients of variation for NE and E are 10 and 16% in a human plasma sample containing low catecholamine levels. The assay permits quantitation of plasma E levels that were undetectable in prior assays. PMID- 2266784 TI - Interaction of circadian rhythm and opiate-induced thermic and kinetic responses: a biotelemetric investigation. AB - The thermic and kinetic effects of a low dose of morphine sulphate (5mg/kg) were monitored using a remote biotelemetric procedure. Drug and control (saline) injections were administered at two times of day, during the high and low phases of the circadian temperature/activity cycle respectively. Standard measures of the responses revealed that the effect of a dose of morphine differs significantly according to the phase of the circadian rhythm in which it is administered. In contrast to previous studies employing standard stress-inducing rectal probing techniques of temperature measurement, the direction and time course of thermic and kinetic responses were uncorrelated. The implications for research on physiological and behavioral drug effects and for theories of drug tolerance/dependence are considered. PMID- 2266785 TI - The molecular basis of cannabinoid activity. AB - Cannabinoids have been known to exhibit a wide variety of biological effects. Over the past fifty years numerous analogs were synthesized in an attempt to understand the structural requirements for each cannabinoid activity. Only recently, however, some important findings have focused new attention on this field of research. These findings include: (a) The development of novel "non classical" potent cannabinoid analogs which exhibit similar pharmacological profiles with their "classical" counterparts; (b) The demonstration that there are specific cannabinoid binding sites in cell cultures as well as in mammalian brains; (c) Biophysical studies related to the interactions of cannabinoids with membranes which lead to a better understanding of those molecular properties which are required for cannabinoid activity; (d) Detailed and uniform pharmacological testing on a sizeable number of analogs allowing for a more detailed dissection of the cannabinoid effects and respective "structure activity relationships." The newly increased interest in cannabinoid research opens the door for a better understanding and potential treatment in cases of abuse as well as novel therapeutic opportunities through the design and synthesis of pharmacologically more selective analogs. PMID- 2266786 TI - Effects of peripheral administration of recombinant human interleukin-1 beta on feeding behavior of the rat. AB - This study was undertaken to investigate the changes in feeding behavior, including ambulatory activity, induced by a single injection of Interleukin-1 beta (IL-1) (2 micrograms/rat) at 18:00, just before the dark phase. For this purpose, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. A significant decrease in food intake was observed for 12 hours after treatment with IL-1. Peripheral administration of IL-1 also produced a marked decrease in ambulatory activity within 3 hours which continued for 6 hours. In addition, IL-1 produced a marked decrease in drinking behavior during the first 6 hours. We reported here the changes in consummatory and ambulatory behavior of rats after acute administration of IL-1. The sickness which IL-1 produced may, at least in part, contribute to these phenomena, although precise mechanisms are still unknown. PMID- 2266787 TI - Significant increase of interleukin 6 production in blood mononuclear leukocytes obtained from patients with active inflammatory bowel disease. AB - In the present study, we compared the potency of interleukin 6 production in peripheral blood mononuclear leukocytes between paired patients with active stage and inactive stage of inflammatory bowel disease. Subjects included nine patients with ulcerative colitis, ten patients with Crohn's disease and sex-matched nine healthy volunteers. Mononuclear leukocytes were stimulated with concanavalin A for 24 h to induce interleukin 6 production. Interleukin 6 content in the culture medium was assayed by using specific ELISA and interleukin 6 dependent cell line MH-60. Interleukin 6 production was found to be significantly increased in mononuclear leukocytes from both active ulcerative colitis and Crohn's disease as compared to that from control subjects. There was no significant difference in interleukin 6 production between ulcerative colitis and Crohn's disease. The potency of interleukin 6 production was returned to the control level when the diseases became inactive. The present results, therefore, may indicate some important role of interleukin 6 in the pathogenesis of inflammatory bowel disease and also the potency of interleukin 6 production in mononuclear leukocytes can be an indicator of the activity of inflammatory bowel disease. PMID- 2266788 TI - Hemolysis of rabbit erythrocytes induced by cigarette smoke. AB - Cigarette smoke has been found to induce the hemolysis of rabbit erythrocytes. The particulate phase had more profound effect than the gas phase. Neither free radical scavengers such as ascorbic acid, uric acid and water-soluble vitamin E analogue nor antioxidant enzymes such as catalase and superoxide dismutase suppressed the cigarette smoke-induced hemolysis, suggesting that free radicals, hydrogen peroxide, and superoxide were not the active species. PMID- 2266789 TI - Pressor effect of NG-nitro-L-arginine in pentobarbital-anesthetized rats. AB - The pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, was studied in pentobarbital anesthetized rats. Iv injections of L-NNA from 0.25 to 8 mg/kg caused bradycardia and a dose-dependent increase in mean arterial pressure (MAP) with a maximal response of 43 +/- 5 mmHg and ED50 value of 1.3 +/- 0.2 mg/kg. The time course of the response to the injection of a single dose of L-NNA was also determined. Peak response was reached 60 min after the injection of a single dose (4 mg/kg, iv) and the effect lasted greater than 5 h. The rising phase of the pressor response was accompanied by slight bradycardia while the recovery phase was associated with significant tachycardia. Iv injections of L-arginine (12.5-200 mg/kg) caused transient dose dependent reductions in MAP. The pressor effect of L-NNA (4 mg/kg, iv bolus) was dose-dependently attenuated by L-arginine. The results show that L-NNA is an efficacious and long-acting pressor agent and are consistent with the hypothesis that endogenous NO plays an important role in the regulation of blood pressure. PMID- 2266790 TI - Aging and sex influence the permeability of the blood-brain barrier in the rat. AB - The aim of the present study was to investigate the existence of aging- and sex related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels. PMID- 2266792 TI - Wireless retrospective gating: application to cine cardiac imaging. AB - A new "wireless" method of cardiac imaging is introduced, which, unlike ECG triggering, allows imaging the heart at end-diastole, and greatly reduces smearing artifacts in the phase-encoding direction. It is an improvement over ECG driven retrospective gating, in that patients with poor ECGs can be imaged. This method extends the applicability of cardiac imaging, and since it requires no physiological monitoring hardware, can be implemented easily on any MR imager. The images produced by this method are superior to those from ECG triggering, especially when viewed in a "cine" loop. The technique described herein is, furthermore, extendable to any area where periodic or quasi-periodic motion is a problem. PMID- 2266791 TI - Chronopharmacological study of furosemide; (VII). Influence of repeated administration on biochemical parameters in blood. AB - The present study was undertaken to examine whether influences of furosemide on biochemical parameters vary with its time of administration in Wistar rats. Rats were maintained under conditions of light (0700-1900 hrs) and dark (1900-0700 hrs). Furosemide (30 mg/kg) or vehicle (5% glucose) was given orally at 1000 hrs (day trial) or at 2200 hrs (night trial) for 14 days. Water and food intakes were measured, and urine was collected for 24 hours following the final dosage in each group. Thereafter, blood samples were obtained. Water intake and urinary excretions of volume, sodium and chloride increased by furosemide treatment. The increments in these parameters were greater in the day trial than in the night trial. Food intake did not change. The serum concentration of chloride was decreased by furosemide. The decrement in this parameter was enhanced in the day trial. The influence of furosemide on other biochemical parameters (sodium, potassium, creatinine, calcium, inorganic phosphate, total protein, total cholesterol and glucose) did not differ between the day and night trials. These data indicate that the untoward influence of furosemide on serum chloride might vary with its time of administration. PMID- 2266794 TI - Spin-lattice relaxation times and nuclear Overhauser enhancement effect for 31P metabolites in model solutions at two frequencies: implications for in vivo spectroscopy. AB - The relaxation time T1 values and nuclear Overhauser enhancement factor for 31P signal were determined in model solutions of metabolites ATP, PCr and Pi, and AMP at two frequencies and in H2O and 2H2O solutions. The data were analyzed to resolve the contribution of different relaxation mechanisms. A knowledge of NOE is important in the light of recent applications of double resonance methods to enhance the sensitivity of in vivo 31P spectroscopy. The results show that chemical shift anisotropy is the dominant mechanism for 31P in ATP at the high field, whereas the dipolar interaction mechanism is the main feature for the 31P relaxation of PCr and Pi. The dipolar mechanism responsible for NOE originates from interactions of solvent water with 31P moiety. Implications for in vivo spectroscopy are indicated. PMID- 2266793 TI - Gadolinium-DTPA-enhanced MRI of intraocular tumors. AB - The value of gadolinium-enhanced MRI in 30 patients with intraocular lesions has been evaluated. Seventeen patients had a uveal melanoma, two a ciliary body melanoma, three had uveal metastases, one lymphoma, four had senile macula degenerations, and three uveal nevi. Twelve of 17 patients with melanoma were followed up by MRI after ruthenium plaque therapy on 2-4 occasions. Melanomas showed high precontrast signal intensities and only a slight enhancement after intravenous Gd-DTPA was given. After ruthenium plaque therapy precontrast signal intensities (SI) decreased while a moderate signal increase on postcontrast scans was noted. Scars or tumor residues were better delineated on enhanced images. All other tumors than melanotic melanomas showed low SI on precontrast scans and a high signal increase after Gd-DTPA administration. Small amelanotic tumors were better delineated on postcontrast scans. In addition Gd-DTPA-enhanced MRI allowed differentiation between tumor and hemorrhage. No signal increase after Gd-DTPA application was seen in subretinal or vitreous hemorrhages of varying ages. PMID- 2266795 TI - Magnetic resonance imaging as an adjunct to sonography in the evaluation of the female pelvis. AB - Magnetic resonance imaging (MRI) of the pelvis is generally considered to be most beneficial in those cases where the pelvic sonogram is limited or equivocal. All cases that underwent both sonographic and MRI examinations at our institution for the evaluation of the female pelvis in the past two years were retrospectively reviewed. We reviewed the sonographic and MRI reports and the subsequent clinical management in the 41 cases that had both studies to assess whether MRI contributed to the clinical management decision. Both studies were interpreted independently based upon the known clinical and laboratory data available at the time. MRI was obtained in 21 cases because the sonogram was suboptimal or inconclusive. In the other 20 cases it was obtained for additional information, even though the sonogram was diagnostic. Of the 21 inconclusive sonographic studies, MRI established or clarified the diagnosis in all cases. Of the 20 studies where MRI was obtained for additional information, MRI added useful data that helped contribute to the clinical management of 11 patients. MRI is an important adjunct to pelvic sonography. It established, clarified, or added significant data in 78% of cases. PMID- 2266796 TI - Fiber-to-field angle dependence of proton nuclear magnetic relaxation in collagen. AB - Longitudinal and transverse proton relaxation times were measured on pig tendon. For T1, dispersion curves and more accurate measurements at 20 MHz are presented. Values of T2 were obtained from CPMG pulse sequences, at 20 MHz. The dependence of relaxation times against the fiber-to-field angle was particularly investigated. Longitudinal relaxation rate was found to be almost orientation independent, and presented quadrupolar peaks between 1 and 4 MHz. On the contrary, transverse relaxation, that was well fitted by the sum of four exponentials, was highly orientation dependent. Deconvolution showed that the exponentials decaying most quickly are most orientation dependent. For those two fractions, a cross-relaxation model allowed explaining the fiber-to-field angle dependence, and the specially low rate corresponding to the magic angle of 55 degrees. Finally, each decaying mode was assigned to a fraction of protons localized in the macromolecular structure and characterized by particular dynamics. PMID- 2266797 TI - The application of proton nuclear magnetic resonance imaging for the in vivo characterisation of chemically induced renal lesions in rats over a prolonged time study. AB - Renal cortical and medullary spin-lattice (T1) relaxation times were measured at various time points over a period of 56 days following the administration of a single i.p. injection of 100 mg/kg 2-bromoethanamine hydrobromide (BEA), 200 mg/kg hexachloro-1,3-butadiene (HCBD) or 100 mg/kg puromycin aminonucleoside (PAN) to male Wistar rats. Administration of a single injection of HCBD caused a dramatic, immediate rise in the cortical T1 values above control values, and these levels remained elevated until, by Day 28 postinjection the levels were back to control values. Administration of BEA also caused an elevation in cortical T1 values, but in this case these values remained above control values for the rest of the study. The administration of PAN did not produce any significant increases in cortical T1 values until 14 days postinjection. The elevated T1 values remained above control values for the rest of the study. These increases observed in cortical T1 values appeared to be mirrored by decreases in medullary T1 values. Increases in cortical T1 values were accompanied by visual changes in the NMR images and enlargement of the kidneys. The histological findings were consistent with the NMR data, confirming that morphologically the tissues did show a full recovery by Day 28 in the HCBD-treated animals. This was not the case following injection of both BEA and PAN, where necrosis was not reversible and there was no recovery of the tissues. PMID- 2266798 TI - A technique for flow-enhanced magnetic resonance angiography of the lower extremities. AB - A two-dimensional, flow-enhanced gradient echo pulse sequence for nuclear magnetic resonance angiography is described. It employs interleaved, presaturated slices to acquire data efficiently on imagers which favor interleaved acquisition over sequential acquisition for multislice imaging. It is useful on any imagers when the effective TR is extended to enhance the sensitivity to slow flow. The technique was applied to the region from aortic bifurcation to the iliac bifurcations of three normal volunteers. The right and left common iliac arteries and veins, the separation of the external and internal iliac arteries, and secondary branches were clearly depicted. PMID- 2266799 TI - A novel editing technique for 19F MRI: molecule-specific imaging. AB - A novel technique is proposed to facilitate the selective imaging of specific molecules from a mixture. The application of the technique presented here demonstrates the ability to selectively produce 19F MR images of either trifluoroacetic acid or the perfluorocarbon emulsion Oxypherol-ET (perfluorotributylamine), when both molecules are present simultaneously. Selective detection is based on the presence of homonuclear J-modulation in one molecule and differential spin-spin relaxation time (T2). Perfluorotributylamine, an A3B2 system, is subject to homonuclear J-modulation, which produces a null signal from the antiphase components of the triplet (A3) when an echo time (TE) = 1/2J is used in a spin-echo image. At this echo time the second molecule, in this example trifluoroacetic acid, a non-coupled spin system, is selectively imaged. At longer echo times, e.g., TE = 1/J there is substantial recovery of the J modulated signal, which may be solely observed due to T2 decay of the trifluoroacetic acid signal. The method is demonstrated both using phantoms and in vivo. PMID- 2266800 TI - Predictability of SNR and reader preference in clinical MR imaging. AB - Fifty-four independent scans were performed in two volunteers covering one anatomic region in each (the brain and knee) with the purpose of ascertaining the agreement between predicted and measured signal-to-noise ratios (SNR). Systematically varied parameters were number of excitations (NEX), field of view (FOV), section thickness (dz), and the number of phase-encoding steps (Ny). Correlation coefficients of measured versus predicted SNR were 0.82 and 0.86, respectively, in the anatomies studied. Significantly improved correlations were found for data subpopulations in which NEX was held constant. To assess the criteria guiding reader preference, a blinded study was performed in which radiologists were asked to rate images from least to most desirable. In order to quantitatively determine the criteria for reader preference, plots of mean rating versus SNR, voxel volume, and an image quality index [IQI = SNR/(voxel volume)] were performed. The latter was found to be a better predictor of reader preference than either SNR or spatial resolution alone. The data suggests T1 weighted scan protocols yielding SNR of approximately 20 are preferable with any excess SNR being traded for smaller voxel size or shorter scan times. PMID- 2266801 TI - Magnetic resonance imaging of the thoracic cavity using a paused 3DFT acquisition technique. AB - A new pulse sequence designed for magnetic resonance imaging of the entire thoracic cavity is described. This sequence, called 3DPAUSE, is a rapid three dimensional Fourier transform (3DFT) sequences with periodic pauses for breathing and additional rf pulses after each pause to restore the magnetization to steady state before data acquisition resumes. Cardiac motion artifacts are effectively removed by signal averaging. Respiratory motion artifacts are removed by breath hold. Image artifacts caused by an inadequate number of pauses or by inappropriate placement of the pauses within a scan are shown, and ways to avoid these artifacts are discussed. 3DPAUSE provides the ability to acquire three dimensional arrays in the thoracic cavity with minimal artifacts from respiratory and cardiac motions in a clinically reasonable time. PMID- 2266802 TI - The effects of restricted diffusion in nuclear magnetic resonance microscopy. AB - A stochastic computer simulation is used to investigate the effects of restricted diffusion in NMR microscopy. It is shown that diffusion contributes to a loss of interfacial resolution through two main mechanisms. The first applies to spatial regions bound by impermeable interfaces and involves diffusive averaging of the frequency differences set up by the applied field gradients. This effect can be made arbitrarily small by increasing the magnitude of the field gradient. The second mechanism involves diffusion through permeable membranes or interfaces defining the sample morphology. This effect can, in principle, be reduced by multiple echo imaging with short pulse spacings. The possibility of imaging diffusive flow through a permeable interface is discussed. PMID- 2266803 TI - Slice profile improvement for a clinical MRI system. AB - Optimal control methods have been recently introduced to improve the design of selective radio frequency pulses and several optimized selective pulses that can produce excellent slice profiles have been reported. These pulses usually require high peak rf amplitudes to implement and thus can not be widely utilized because of the limitations of the specific absorption rate and the rf power amplifier of a clinical system. We have a Siemens 1.5 T MRI clinical system. Several pulse files which consist of the bandwidth matched 90 degrees and 180 degrees selective pulses are provided. Some of these can produce excellent slice profiles. However, they can only be used in the pulse sequences with the pulse length of 5.12 msec. The purpose of this paper is to improve the slice profiles produced by the pulse file in the pulse sequences with the shorter 2.56 msec pulse length. A pulse file optimized by the conjugate gradient method is proposed to substitute the 2.56 msec Siemens pulse file. Our experimental results confirm that the slice profiles and images are improved by the optimized pulse file with a lower peak voltage. The proposed pulse file can also be applied in other clinical MRI systems. PMID- 2266804 TI - Changes in MR signal intensity and contrast enhancement of therapeutically irradiated soft tissue. AB - Increased MR signal intensity was observed on T2-weighted, STIR, and Gadolinium DTPA-enhanced T1-weighted images of subcutaneous and muscular soft tissue in 9 of 10 children treated with combination chemotherapy and radiation therapy (RT) for malignancy in the pelvis or an extremity. Total radiation doses ranged from 59.5 to 65 Gy. Eight of the patients with these changes received hyperfractionated RT (seven for Ewing sarcoma and one for perineal rhabdomyosarcoma); one was treated for pelvic hemangiopericytoma with once-daily fractions. Evidence of soft tissue damage became apparent as early as the sixth week of RT and was seen for up to 69 wk post-RT. There was no clear MR evidence of RT-induced soft tissue damage in one patient, who underwent hyperfractionated RT for pelvic rhabdomyosarcoma. Other MR findings in this group included evidence of bladder wall thickening in three of the seven patients given pelvic RT and increased T1-weighted signal of irradiated marrow in nine patients. All patients had clinical evidence of skin, soft tissue, or epithelial radiation effects. Increased MR signal intensity secondary to RT-induced damage can be differentiated from widespread tumor by geometric borders that conform to the margins of the radiation field. PMID- 2266805 TI - Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia. AB - Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T1 and T2 for the "water" and "fat" resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The "relative water content" was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T1 relaxation times of the "water" resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patient showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow. PMID- 2266807 TI - Approach to equilibrium in snapshot imaging. AB - The snapshot FLASH sequence uses a subsecond scan time and a small flip angle in conjunction with nonsteady-state acquisition to produce high-contrast images with minimum motion artifacts. The magnetisation evolves towards an equilibrium state in the course of a scan and it is the form of this approach to equilibrium which determines the contrast and signal-to-noise ratio (SNR) obtained. The contrast obtained is strongly dependent on the phase encoding scheme used. If the flip angle is increased, and the resulting transverse coherences refocused, then the SNR is improved while the contrast is little changed. PMID- 2266806 TI - Magnetic resonance imaging and computed tomography in Pelizaeus-Merzbacher disease. AB - Six patients with the classical form of Pelizaeus-Merzbacher disease (PMD) were studied with computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. While final diagnosis of PMD should be made on the basis of histopathologic findings in the brain, findings in this group support the fact that MRI can be used for tentative early diagnosis when computer tomographic examination is normal or nondiagnostic. All patients had MRI findings reflecting a pattern of diffuse white matter disease that can be considered characteristic in the appropriate clinical setting. PMID- 2266808 TI - MRI and diabetic foot infections. AB - The role of magnetic resonance imaging and plain radiographs in evaluating osteomyelitis in the diabetic foot was studied. Fifty patients were prospectively examined by magnetic resonance imaging and plain radiographs to determine the extent of infection. Thirty-seven patients had positive MRI for osteomyelitis and 19 were positive with conventional radiography. Thirteen patients had negative MRI healed with short course of antibiotics. Five patients with positive MRI received four weeks' course of intravenous antibiotics with two still having persistent infection in the six weeks follow-up. Thirty-two patients underwent surgery with favorable results. Sixty-two bone specimens were obtained for histologic evaluation of osteomyelitis. In cases with histologic proof of diagnosis, magnetic resonance sensitivity was 99%, specificity was 81%, and accuracy was 94%. Thus magnetic resonance imaging was shown to have a high sensitivity, specificity, and accuracy in detecting osteomyelitis. PMID- 2266809 TI - Varied MR appearance of autism: fifty-three pediatric patients having the full autistic syndrome. AB - Fifty-three autism patients ranging in age from 2 to 22 yr with a mean age of 9 yr were evaluated by MR imaging over a 3-yr study period. Sagittal, axial, and coronal spin-echo and short TI inversion recovery scans were performed on a 0.5 Tesla (Picker Inc., Cleveland, OH) system. Results were compared to 32 control patients age range 1 to 17 yr, mean 8.5 yr. MR scans were evaluated by three neuroradiologists. Measurements of midsagittal vermian height and AP diameter were performed. Subjective estimates were made of ventricular size, amygdala size, fourth ventricular size, and vermian shape. Results were correlated with clinical presentation, course, and lab analyses by a pediatric neurologist. MR findings did not present a single pattern capable of predicting the presence or severity of autism. The constellation of MR findings in this group of 53 patients was highly variable, thus we advise caution in the interpretation of MR images in autistic patients. Autism is a heterogeneous disease entity containing different clinical subgroups, which do not manifest similar radiologic pictures. PMID- 2266810 TI - Severe anaphylactoid reaction after i.v. Gd-DTPA. AB - Serious adverse reactions following the IV administration of Gd-DTPA (Magnevist, gadopenetate dimeglumine, Berlex Laboratories, Wayne, NJ), although extremely rare, can occur. As yet, there has been no published case of a severe anaphylactoid-type reaction to Gd-DTPA. PMID- 2266812 TI - Cardiac lipoma: six-year follow-up with MRI characteristics, and a review of the literature. AB - A total of 63 cardiac lipomas have been reported to date. Although most of these rare tumors cause no symptoms, a few can have a detrimental effect on myocardial function as well as displacing and encasing the coronary arteries. This case of a cardiac lipoma was initially seen in 1982. The lipoma was found to be nonresectable at surgery due to involvement of the coronary arteries. This neoplasm was characterized with magnetic resonance imaging in 1989 on a follow-up visit. Magnetic resonance imaging is shown to be superior to computed tomography for identifying the relationship of the lipoma to the coronary arteries. This is a significant factor in determining resectability. PMID- 2266811 TI - Cerebral abnormalities in Wilson's disease as evaluated by ultra-low-field magnetic resonance imaging and computerized image processing. AB - The cerebral involvement of a 13-yr-old boy with Wilson's disease was serially evaluated during the first 18 mo of D-penicillamine treatment. An ultra-low-field magnetic resonance imaging (ULF MRI) system, operating at 0.02 T, with computerized image processing was used. The half-yr period prior to the clinical diagnosis was set, the patient had showed poor school performance, emotional lability, deteriorating handwriting, progressively slow, gross, and fine motor functions, and a fixed rigid smile. No overt signs of liver disease were found. With D-penicillamine treatment (1-1.5 g/d) a continuous improvement was seen. The pretreatment MRI investigation showed pronounced pathological transformation in the basal ganglia. However, changes were seen also in most other parts of the brain indicating diffuse involvement. During treatment the computerized MR images became gradually more normal. The current magnetic resonance imaging system with computerized image processing is a sensitive and simple method for evaluation of subtle parenchymal changes of the brain. PMID- 2266813 TI - Advances in cardiac applications of subsecond flash MRI. AB - Flow-suppressed, subsecond FLASH MR images of the normal human heart have been obtained from single cardiac cycles using a 2.0-T whole-body MRI/MRS system (Siemens Magnetom) equipped with conventional 10 mT m-1 gradients. The present results demonstrate further technical improvements as compared to a previous report on the same subject (Magn. Reson. Med. 13:150-157; 1990). Measuring times of 139 msec and 209 msec were achieved by reducing the repetition time to TR = 4.36 msec (TE = 2.8 msec) and the spatial resolution to 32 x 128 or 48 x 128 measured data points, respectively. The flip angle was optimized to 12 degrees. Spatial pre-saturation of 60 mm thick sections adjacent to the imaging plane resulted in a suppression of the blood signal and a clear delineation of the myocardium. Oblique rotation of the imaging slice provides convenient access to the anatomical long axis and short axis views of the heart. EKG-triggered images from separate heartbeats but at different cardiac phases demonstrate that the effective time resolution is considerably less than the actual imaging time. PMID- 2266814 TI - One minute with diabetes. Meal planning. PMID- 2266815 TI - Intensification of adjuvant chemotherapy in patients with primary breast cancer and positive axillary nodes. PMID- 2266816 TI - Chinese medicine and politics: Mao to Tiananmen. PMID- 2266817 TI - Sigmoid endometriotic stricture treated with endoscopic balloon dilatation: case report and literature review. PMID- 2266818 TI - Amebic liver abscess: review of twenty-nine cases with an evaluation of imaging techniques. AB - Twenty-nine patients with amebic liver abscess were reviewed retrospectively. In twenty-six of twenty-eight patients, ultrasonography demonstrated the abscess. An elevated indirect hemagglutination titre confirmed the diagnosis in twenty-seven of twenty-eight patients. All patients recovered with specific chemotherapy. In evaluating clinically suspected amebic liver abscess, ultrasonography is a cost effective, readily available, and reliable imaging method. If needed, computed tomography provides confirmation. Needle aspiration or catheter drainage have questionable value unless the diagnosis is in doubt or extrahepatic spread is present. The indirect hemagglutination test shows an elevated titre in most patients with liver infestation. By inducing a prompt recovery, antiamebic chemotherapy can confirm a suspected clinical diagnosis. PMID- 2266819 TI - John Archer: first medical graduate of the New World. PMID- 2266820 TI - Drug testing of employees. PMID- 2266821 TI - Dr. Osler and the Book and Journal Club of the Medical and Chirurgical Faculty of Maryland. PMID- 2266822 TI - [The medical sequelae of the radiation accident in the Southern Urals in 1957]. AB - As a result of an accidental outburst of long-lived radionuclides at the nearest zone of the trace, a dose rate of gamma-radiation was several dozen CGy/h and in the open country at some populated areas it was 0.1 CGy/h. The evacuation of 10730 persons permitted a decrease of possible radiation doses 2-24-fold. A follow-up of persons who had been exposed to the highest effective equivalent doses of radiation before the evacuation revealed unstable indices of leukocytes and platelets (however they were within normal variations) in the first 2 years. Morbidity and mortality rates among the adults, the rates of congenital diseases and pediatric mortality did not differ from the control values. The rate of families having children born from persons aged 10 to 30 at the time of the accident did not differ from the similar rates for the USSR; this rate was lower by 5-10% than the control values for persons aged 0 to 9 at that time. Standardized birth rates in the study group (31 x 8,10(-3)) were much higher than in the control group (18 x 4,10(-3)). PMID- 2266823 TI - [An assessment of the contribution of internal irradiation to the early manifestations of acute radiation sickness in the victims of the accident at the Chernobyl Atomic Electric Power Station]. AB - Materials of the investigation of victims of the accident at the Chernobyl Nuclear Power Plant were used for the estimation of a contribution of exposure with incorporated radionuclides to a course of acute radiation syndrome thyroid and pulmonary lesions. Attention was granted to patients who died as a result of accidental exposure. Dose values of thyroid, pulmonary and total body exposure were given. The severity of the affection of the bronchopulmonary and hypophysial thyroid systems was assessed. The results of cytogenetic investigations to estimate absorbed doses were represented for some persons. Internal exposure was shown to make a considerable effect on the development of acute radiation syndrome in two persons only, internal whole-body exposure doses being compatible with a total exposure dose. PMID- 2266824 TI - [The cerebral hemodynamics in acute radiation sickness developing in the victims of the accident at the Chernobyl Atomic Electric Power Station]. AB - Cerebral hemodynamics was investigated on the basis of rheoencephalography findings in persons with ARD of various degrees of severity in the latent period and during rehabilitation. The data obtained showed correlation of cerebral hemodynamics and a degree of gravity of ARD and a period of development of disease. A decrease in pulse rate, a tendency to increased peripheral resistance and vein tone and an increased rate of cerebral dystonia were marked at the time of rehabilitation of patients with ARD, II-III degree. PMID- 2266825 TI - [The function of the blood reduction systems in people after contact with ionizing radiation at low doses]. AB - An integral rate of a flow of reduction equivalents from intraerythrocytic reducing agents to an external electron acceptor (potassium ferricyanide) was measured to investigate antioxidant capacity of the erythrocytic reducing systems in persons after a contact with small doses of ionizing radiation (0.06-0.25 Cy) 12 mos. before the investigation. A potentiometric method with the help of a redoxstat was employed. Altogether 47 persons (44 men and 3 women) aged 19 to 50 (33.8 +/- 0.96) were investigated. A conclusion is that the condition of the erythrocytic reducing system in persons after a contact with small doses of ionizing radiation can be regarded as normal. PMID- 2266826 TI - [The circulatory system in acute radiation sickness developing in the victims in the accident at the Chernobyl Atomic Electric Power Station]. PMID- 2266827 TI - [The immunological monitoring of patients with acute radiation sickness 12 to 36 months after the accident at the Chernobyl Atomic Electric Power Station]. AB - Immunoassays of the 1st and 2nd levels were investigated in patients with acute radiation disease 12-36 mos. after irradiation. A decrease in the level of helper/inducer T-lymphocytes, a tendency to a decrease in the number of suppressors and an increase in the number of theophylline-stimulated T-cells in patients with acute radiation disease of the 3rd degree were observed. Control of the immune status of this group of patients is recommended. PMID- 2266828 TI - [The effect of the long-term chronic x-ray irradiation of rats on the erythrocyte population composition and hemolytic stability of the peripheral blood]. PMID- 2266829 TI - [A microangiographic study of the damaged liver in acute radiation sickness]. AB - Microangiographic investigation with intravital filling up of the vessels was used to study a course and regeneration of a liver lesion in rats irradiated at a dose of 6 Gy. A traumatic liver lesion is characterized by severe local disorders of blood circulation, sharp vasoconstriction and depletion of the entire liver microcirculatory network. Combined radiation injuries result in phase changes: parenchymal edema, liver microcirculatory depletion in the early posttraumatic period change into relative normalization of the blood circulation of uninjured liver tissue in the latent period. Parenchymal edema, vasodilation and hypostasis reappear at the height of a lesion, followed by rarefaction of the network and vasoconstriction of the microcirculatory bed. Necrotic mass resorption in the period of combined radiation injury is as active as that in unirradiated animals. However at the height of a radiation injury capillary regeneration and necrotic mass resorption cease resulting in retarded regeneration of injured tissues. PMID- 2266830 TI - [The use of radiodiagnostic apparatus as human radiation counters in large-scale radiation accidents]. AB - The problem of dosimetry of internal irradiation necessitates the use of human radiation counters (HRC). A state system of radiation safety should be based on a HRC stock in case of large-scale radiation accidents. Radiodiagnostic units can run in the HRC mode therefore they must be considered as an active reserve widely spread throughout the country. Radiodiagnostic devices can be used for control of the thyroid level of 131I and the whole-body content of a mixture of 134Cs and 137Cs. PMID- 2266831 TI - [Experience in organizing medical care for the victims of the accident at the Chernobyl Atomic Electric Power Station at a specialized hospital]. AB - Organization of health care for victims of radiation accidents requires well adjusted organizational activities, including an inpatient clinic with well equipped reception, dosimetric, karyological and bacteriological laboratories, an intensive care department, a surgical (burn) department, a blood transfusion laboratory and equipment for plasmapheresis and hemosorption. Therapy of such patients should be developed along the following lines: 1) prevention and therapy of infectious complications: 2) blood cell substitution therapy; 3) bone marrow transplantation; 4) detoxicating therapy; 5) correction of water-electrolyte metabolism; 6) therapy of local radiation injuries. PMID- 2266833 TI - Nursing centers: a model for care and reduced costs. PMID- 2266832 TI - [Solomon Naumovich Ardashnikov]. PMID- 2266834 TI - O'er the land of the free. PMID- 2266835 TI - The DOS vs. Unix wars. PMID- 2266836 TI - Private eye and continuous-use clinical computers. PMID- 2266838 TI - The Seventh Annual Medical Hardware and Software Buyers' Guide. PMID- 2266837 TI - Memory management programs for DOS. PMID- 2266839 TI - Cardiac volume. PMID- 2266840 TI - Noise correlations in data simultaneously acquired from multiple surface coil arrays. AB - Multiple images acquired simultaneously from an array of surface coils can be combined to give a composite image with an improved signal-to-noise ratio (SNR) and a large field of view. The composite images' SNR can be optimized by taking advantage of noise correlations between coils and phase shifts induced by surface coil reception. Methods are derived for making optimal composite images with uniform noise or with uniform sensitivity. A simplified model is used to provide an intuitive understanding of the interaction of noise correlation and phase shift phenomena. PMID- 2266841 TI - The NMR phased array. AB - We describe methods for simultaneously acquiring and subsequently combining data from a multitude of closely positioned NMR receiving coils. The approach is conceptually similar to phased array radar and ultrasound and hence we call our techniques the "NMR phased array." The NMR phased array offers the signal-to noise ratio (SNR) and resolution of a small surface coil over fields-of-view (FOV) normally associated with body imaging with no increase in imaging time. The NMR phased array can be applied to both imaging and spectroscopy for all pulse sequences. The problematic interactions among nearby surface coils is eliminated (a) by overlapping adjacent coils to give zero mutual inductance, hence zero interaction, and (b) by attaching low input impedance preamplifiers to all coils, thus eliminating interference among next nearest and more distant neighbors. We derive an algorithm for combining the data from the phased array elements to yield an image with optimum SNR. Other techniques which are easier to implement at the cost of lower SNR are explored. Phased array imaging is demonstrated with high resolution (512 x 512, 48-cm FOV, and 32-cm FOV) spin-echo images of the thoracic and lumbar spine. Data were acquired from four-element linear spine arrays, the first made of 12-cm square coils and the second made of 8-cm square coils. When compared with images from a single 15 x 30-cm rectangular coil and identical imaging parameters, the phased array yields a 2X and 3X higher SNR at the depth of the spine (approximately 7 cm). PMID- 2266842 TI - MR Fourier transform arteriography using spectral decomposition. AB - Reliable separation of arteries from other stationary tissues is accomplished through spectral decomposition by exploiting the pulsatile nature of the blood flow in the arteries. Fourier transformation of a series of projection images in the temporal direction along the cardiac cycle results in spectral images where the arteries are a part of the harmonic component images while stationary tissues and veins are represented as a de component image. From the magnitude of the spectral images an arteriogram can be obtained by summation of the harmonic component images excluding the de component image. This principle is applied to Fourier imaging in a cine mode data acquisition as well as line scan imaging. Since there is no need for the encoding of the flow-sensitive gradient, this technique is free from eddy current artifacts which have been one of the major obstacles to projection angiography using the flow-encoding gradient. PMID- 2266843 TI - High-speed multislice T1 mapping using inversion-recovery echo-planar imaging. AB - Tissue contrast in MR images is a strong function of spin-lattice (T1) and spin spin (T2) relaxation times. However, the T1 relaxation time is rarely quantified because of the long scan time required to produce an accurate T1 map of the subject. In a standard 2D FT technique, this procedure may take up to 30 min. Modifications of the echo-planar imaging (EPI) technique which incorporate the principle of inversion recovery (IR) enable multislice T1 maps to be produced in total scan times varying from a few seconds up to a minute. Using IR-EPI, rapid quantification of T1 values may thus lead to better discrimination between tissue types in an acceptable scan time. PMID- 2266844 TI - NMR visibility of 39K and 35Cl in erythrocytes and kidney tubules. AB - The NMR visibility of 39K and 35Cl has been investigated in erythrocytes and in dog renal tubules. In erythrocytes, the 39K NMR visibility was determined by comparing the signal intensities before and after hemolysis with water and by comparing the NMR and flame photometry results. Both procedures showed a NMR visibility of 100% for intracellular potassium. The visibility of intracellular chloride in erythrocytes was estimated at 40% by monitoring the intensity of the 35Cl signal as a function of the hematocrit value. In the case of kidney proximal tubules, the 39K visibility appeared to be very low but could not be accurately determined due to the low sensitivity of the nucleus. The 35Cl signals for intracellular chloride in renal tubules were too broad to be detected. PMID- 2266845 TI - The slotted crossover surface coil: a detector for in vivo NMR of skin. AB - An elongated, narrow, slotted crossover surface coil provides surface localization capable of resolving in vivo 31P NMR spectra from skin tissues. The shallow B1 field penetration achieves localization objectives while the probe length maintains signal-to-noise requirements. Dielectric and inductive losses are minimized via the crossover design (see T. L. Nagel et al., Magn. Reson. Med. 13, xxx (1990). In vivo spectra with millimeter depth resolution were acquired in 5 min at 2 T without pulse localization sequences. Preliminary 31P NMR spectra of normal and thermally injured rat skin were completed using a 25 X 3-mm slotted probe with a 3 X 2-cm surface region of excitation. Normal rat skin tissue PCr/Pi ratios ranged from 3.8 to 4.7 for 5-, 10-, and 30-mus pulse widths, while partial and full-thickness scald injured tissues ranged from 0 to 2.8. Evaluation of a single minor partial thickness injury 1 to 5 h postburn shows evidence of a localized hypermetabolic response associated with hyperemia. Determination of burn depth and tissue viability appears feasible using: (1) PCr/Pi ratios and (2) observation of localized hypermetabolism. PMID- 2266846 TI - Flow velocity quantitation using inversion tagging. AB - A method for quantitating flow velocities is presented. The technique tags multiple boli of magnetization in transit across a thick selection slab using rf inversion pulses. Results in phantoms and in vivo demonstrate that the method is robust and can provide velocity determinations in tortuous vessels. PMID- 2266847 TI - Tissue perfusion in humans studied by Fourier velocity distribution, line scan, and echo-planar imaging. AB - In tissue perfusion studies, FT velocity distribution imaging (VDI) intrinsically distinguishes signals from moving blood and volume-averaged tissue. Results in human thyroid gland, in vivo, using VDI line scan technique demonstrated separation of moving blood signal from glandular tissue, while VDI inner-volume echo-planar imaging of brain showed only CSF velocity above the image noise level. New alternating polarity gradient sequences which permit separation of diffusion and slow velocity are discussed. A novel method of 3D FT imaging (two spatial and one velocity dimension) combining inner-volume imaging and echo planar imaging with velocity resolution of 0.15 mm/s per pixel is demonstrated. A novel graphical method of calculation and display of diffusion dependence in pulsed gradient sequences is presented. PMID- 2266848 TI - Computer modeling of surface coil sensitivity. AB - A simple model is presented for the calculation of relative signal-to-noise (S/N) ratios of coils of different sizes and configurations when applied to in vivo MRS. Axial symmetry is assumed, which enables rather simple expressions to be used for the calculation of coil loading by the tissue. The model is calibrated to experiments through measurement of the loaded and unloaded coil Q's. Applications of the model demonstrate that for small, superficial regions of interest (ROI), small surface coils can provide a S/N much improved over that of a larger coil. However, for very deep ROIs, larger coils or coils producing uniform B1 provide improved S/N. PMID- 2266849 TI - PC-based system for retrospective cardiac and respiratory gating of NMR data. AB - A method and a means for retrospectively clustering NMR k-space measurement profiles with respect to both cardiac and respiratory phases were developed to explore strategies for (1) reducing cardiovascular and respiratory flow/motion image artifacts and (2) improving T1 and T2 characterization of the heart. The image data are collected at a uniform rate so that echo (TE) and repetition (TR) times are independent of the varying cardiac cycle R-R interval and/or respiratory motions. Cardiac (C) time, respiratory (R) time or diaphragm position, and NMR data acquisition (A) cycle time are collected by microcomputer in parallel with free running (untriggered) image collection on a standard magnetic resonance imager. After the raw data equivalent of multiple images are collected, the C-A-R phase timing data are uploaded from the microcomputer to the scanner's minicomputer for use in a normalized C-R phase plane clustering of the image raw data. Each profile's position in the C-R phase plane is determined and then clustered into a new set of data, one image being equivalent for each desired C-R phase combination. These raw data are then zero-filled and (optionally) filtered to compensate for the nonuniform k-space sampling and, finally, reconstructed. Cardiac "cines" made from these retrospectively gated images are comparable to similarly phased triggered images. When high time resolution is required, retrospective gating can be expected to show improvements over triggering, especially toward the critical latter part of the cardiac cycle, where coronary artery filling occurs. The system described can readily be assembled from generally available components. PMID- 2266850 TI - Nuclear relaxation of human brain gray and white matter: analysis of field dependence and implications for MRI. AB - The dependence of 1/T1 on the magnetic field strength (the relaxation dispersion) has been measured at 37 degrees C on autopsy samples of human brain gray and white matter at field strengths corresponding to proton Larmor frequencies between 10 kHz and 50 MHz (0.0002-1.2 T). Additional measurements of 1/T1 and 1/T2 have been performed at 200 MHz (4.7 T) and 20 MHz (0.47 T), respectively. Absolute signal amplitudes are found to be proportional to the sample water content, not to the "proton density," and it is concluded that the myelin lipids do not contribute to the signal. Transverse magnetization decay data can be fitted with a triple exponential function, giving characteristic results for each tissue type, and are insensitive to variations of the pulse spacing interval. The longitudinal relaxation dispersion curves show characteristic shapes for each tissue type. The most striking difference is a large dispersion for white matter at very high fields. As a consequence, the relative difference in 1/T1 between gray and white matter shows a marked maximum around 10 MHz. Possible implications for MRI are discussed. A weighted least-squares fit of the dispersions has been performed using a four-parameter function of the form 1/T1 = 1/T1,w + D + A/(1 + (f/fc)beta'). The quality of the fit is superior to that of other functions proposed previously. The results of these fits are used to predict image contrast between gray and white matter at different field strengths. PMID- 2266851 TI - Spatial mapping of 23Na NMR signals by two-dimensional rotating frame imaging. AB - The reconstruction of two-dimensional spatial images with 0.5-mm resolution using radiofrequency gradients generated by an NMR coil system rotated about the sample is demonstrated for 23Na. The method retains chemical shift, should be capable of mapping T1 and T2 information, and might offer sensitivity advantages for nuclides with short T2. PMID- 2266852 TI - Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes. AB - It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1 [theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil. PMID- 2266853 TI - In vivo flow 31P FT-NMR spectroscopy of a nematode parasite. AB - 31P NMR spectroscopy of a parasitic nematode. Steinernema carpocapsae, is described. In vivo spectra were generated from nematode suspensions continuously circulating through the spectrometer. By flowing the organism, saturation effects were avoided and short interpulse delays significantly reduced spectral generation time. To maximize sensitivity, 90 degrees pulses were employed. Changes in energetic status in response to oxygen availability were easily and rapidly monitored in circulating nematodes. PMID- 2266854 TI - Activation of the human complement system by phenolic glycolipid 1 of Mycobacterium leprae. AB - The activation of the complement system by phenolic glycolipid 1 (PGL) from Mycobacterium leprae was studied. It was found that PGL consumed haemolytic complement through both the classical and the alternative pathways. This was further studied at the level of C3. Although the activation was independent of anti-PGL antibodies present in normal human serum, the addition of antibody augmented the activation of complement by PGL. The uptake of C3 through the classical pathway was enhanced predominantly by IgM antibody whereas, IgG antibody against PGL was responsible for the augmentation of the alternative pathway activation. Furthermore, it was found that both the disaccharide and trisaccharide components of PGL were able to activate the complement system. PMID- 2266855 TI - Construction of an auxotrophic Shigella flexneri strain for use as a live vaccine. AB - A virulent Shigella flexneri serotype Y strain, SFL1, was made auxotrophic for aromatic metabolites, including p-aminobenzoic acid, which is not available in mammalian tissues, by transduction of a Tn10-inactivated aroD gene from Escherichia coli K-12 NK5131. One transductant, SFL114, selected for further studies, had the same biochemical and serological characteristics as the parent strain and the O-antigen patterns of the two strains were identical in SDS-PAGE and Western blot experiments. SFL114 was as invasive for cultured epithelial cells as SFL1, and both strains could escape from the phagocytic vacuole into the cytoplasm of the infected cells. However, the ability of SFL114 to multiply intracellularly was considerably reduced. When applied to the conjunctival sac of guinea pigs, the parent strain gave rise to keratoconjunctivitis, i.e. was Sereny positive, in 13 of 16 animals. By contrast, SFL114 was Sereny-negative in all 11 guinea pigs tested. These in vitro and in vivo results suggest that the aromatic dependent transductant S. flexneri SFL114 is attenuated and possesses properties desirable for a live vaccine. PMID- 2266856 TI - Binding of a Staphylococcus aureus bone pathogen to type I collagen. AB - We contrasted the collagen-binding potential of the experimental osteomyelitis pathogen, Staphylococcus aureus strain SMH, to several other strains. These included Cowan 1 (binder), Wood 46 (non-binder) and six capsular variants. These measurements were made using an 125I-collagen binding assay. Formalin-killed S. aureus SMH strongly bound commercial type I iodinated collagen (dissociation constant, Kd = 2 x 10(-9) M). The extent of binding was similar to Cowan 1. Binding was saturable and not inhibited by 100 mM solutions of D-glucose, D galactose, D-mannose, methyl-alpha-L-fucopyranoside, L-hydroxyproline or L glycine. D-lactose gave moderate inhibition of binding to collagen, and L-fucose was strongly inhibitory. Trypsinized SMH did not bind collagen. None of four Ruthenium-red-staining staphylococci (encapsulated) avidly bound type I collagen. The encapsulated Smith strain, for example, did not bind to collagen but its capsule-negative variant, Smith compact, showed extensive binding. Three of five non-encapsulated S. aureus were strong collagen binders. These data suggest that the prototype bone pathogen binds to the major protein component of bone's extracellular matrix. Collagen-binding is promoted by protein adhesin(s), not capsule. The latter, in fact, appeared to interfere with this interaction. Binding was inhibited by solutions containing the simple monosaccharide, L fucose. PMID- 2266857 TI - Not all nonwords are alike: implications for reading development and theory. AB - Three experiments were designed to examine children's and adults' ability to pronounce consonant-vowel-consonant (CVC) nonsense words. Some of the nonwords, like tain and goach, shared their VC unit with a number of real words. Other nonwords, like goan and taich, shared their VC unit with few or no real words. Pooling across items, the very same grapheme-phoneme correspondences occurred in the two types of nonwords. First graders, good and poor third grade readers, and adults all performed better on the nonwords with the more common VC units than on the nonwords with the less common VC units. Although readers appeared to use VC units in the pronunciation of nonwords, we did not find evidence for use of initial CV units. Implications of the results for reading development, dyslexia, and models of nonword pronunciation are discussed. PMID- 2266858 TI - Encoding information for future action: memory for to-be-performed tasks versus memory for to-be-recalled tasks. AB - What is the nature of the representation underlying memory for future tasks such as calling the doctor or buying milk? If this representation consists of a verbal instruction that is translated into action at the time of retrieval, then memory should be better when tested via verbatim recall of the instruction than when tested via actual performance. Three experiments rejected this possibility, indicating better memory for a perform mode of report than for a recall mode of report. This was true in Experiment 1 in which subjects saw a series of verbal instructions (e.g., "move the eraser," "lift the cup," "touch the ashtray"), with advance information regarding the mode of report required during testing. In Experiment 2, the advance cue was valid only in 75% of the trials. Memory depended more heavily on the expected mode of report than on the actual mode of report, suggesting that the perform superiority is due to processes that occur during encoding. In Experiment 3, subjects learned 20 phrases depicting minitasks. More tasks were remembered by subjects tested via performance than by subjects tested via verbatim recall. A second part of Experiment 3 also indicated superior memory when a perform test was expected, regardless of which mode of report was actually required. The results were compared with the finding that subject-performed tasks are better remembered than are their verbal instructions, which suggests that the representation underlying memory for future assignments may take advantage of the imaginal-enactive properties of the envisaged acts. Other possible differences between memory for to-be-recalled tasks and memory for to-be-performed tasks are discussed. PMID- 2266859 TI - Attention and recollective experience in recognition memory. AB - The functional relation between recognition memory and conscious awareness was assessed in an experiment in which undivided attention at study was compared with two divided attention conditions, one more demanding than the other. When recognizing a word from the study list, subjects indicated whether they could consciously recollect its prior occurrence or recognized it on some other basis, in the absence of conscious recollection. Divided attention at study progressively impaired word recognition accompanied by conscious recollection. Recognition in the absence of conscious recollection was not affected by divided attention. These findings are interpreted as providing further support for the idea that recognition memory entails two distinct components, one based on associative and contextual information, the other based on a "traceless" awareness of familiarity. PMID- 2266860 TI - Is memory for spatial location automatically encoded? AB - Naveh-Benjamin (1987, 1988) has shown that memory for spatial location does not meet the criteria for automatic encoding as claimed by Hasher and Zacks (1979). Age, intention, concurrent processing demands, practice, strategies, and individual differences affected memory for location. These variables should have affected effortful but not automatic processing. The experiments reported in the present paper, in which a different task was used, showed that intention, practice, and concurrent processing demands did not affect memory for location. I concluded that (1) the location task used by Naveh-Benjamin included effortful subtasks and also incidental cover or concurrent processing tasks that interfered directly with performance, and (2) the variables that he manipulated may not have affected the encoding of location. The need to differentiate processes from task performance in analyzing the automaticity issue is discussed. The dominant mode for remembering location is automatic, but such information may also be remembered voluntarily. PMID- 2266861 TI - Learning subgoals and methods for solving probability problems. AB - We hypothesize that typical example problems used in quantitative domains such as algebra and probability can be represented in terms of subgoals and methods that these problems teach learners. The "quality" of these subgoals and methods can vary, depending on the features of the examples. In addition, the likelihood of these subgoal's being recognized in novel problems and the likelihood of learners' being able to modify an old method for a new problem may be functions of the training examples learners study. In Experiment 1, subjects who studied examples predicted to teach certain subgoals were often able to recognize those subgoals in nonisomorphic transfer problems. Subjects who studied examples demonstrating two methods rather than one exhibited no advantages in transfer. Experiment 2 demonstrated that if the conditions for applying a method are highlighted in examples, learners are more likely to appropriately adapt that method in a novel problem, perhaps because they recognize that the conditions do not fully match those required for any of the old methods. Overall, the results indicate that the subgoal/method representational scheme may be useful in predicting transfer performance. PMID- 2266862 TI - Recall of order information by deaf signers: phonetic coding in temporal order recall. AB - To examine the claim that phonetic coding plays a special role in temporal order recall, deaf and hearing college students were tested on their recall of temporal and spatial order information at two delay intervals. The deaf subjects were all native signers of American Sign Language. The results indicated that both the deaf and hearing subjects used phonetic coding in short-term temporal recall, and visual coding in spatial recall. There was no evidence of manual or visual coding among either the hearing or the deaf subjects in the temporal order recall task. The use of phonetic coding for temporal recall is consistent with the hypothesis that recall of temporal order information is facilitated by a phonetic code. PMID- 2266863 TI - Levels of representation in the interpretation of anaphoric reference and instrument inference. AB - The level of representation accessed when inferences are made during sentence comprehension was examined. The inferences investigated included antecedent assignment for both definite noun phrase anaphors and pronouns and also instrument inferences. In making these inferences, a listener must access the inferred element, whether an antecedent or an instrument, in either a linguistic form representation or a discourse model. The level of representation involved in these inferences was determined by exploiting differences in the lexical decision and naming tasks, which were argued to exhibit differential sensitivity to representational levels. In three experiments, the priming of antecedent and instrument targets in the lexical decision task was compared with priming of the same targets in the naming task. Differences in the patterns of activation across the two tasks indicated that all three types of inferences required accessing elements in a discourse model. Three control experiments ruled out simple context or congruity checking as an explanation for our results. The following conclusions were also supported by these studies: (1) Antecedent assignment occurs immediately after processing an anaphor; (2) antecedent assignment involves inhibition for the inappropriate antecedent rather than facilitation for the appropriate antecedent; (3) although subjects do not make instrument inferences when they hear isolated sentences containing verbs that strongly imply certain instruments, the inferences are made when sentences are preceded by a context that mentions the instrument. PMID- 2266864 TI - The Tulving-Wiseman law and the recognition of recallable music. AB - Memory for well-known musical phrases was tested first for recognition in the absence of any specific musical context and then for recall given the preceding musical phrase as a contextual cue. Recognition and recall were found to be largely, but not completely, independent. Moreover, there was no evidence of any greater dependency between recognition and recall than that previously observed in the relation between word recognition and recall, as summarized by the Tulving Wiseman law. These findings significantly extend the range of applicability of this law. PMID- 2266865 TI - Common processes underlie enhanced recency effects for auditory and changing state stimuli. AB - For some stimuli, dynamic changes are crucial for identifying just what the stimuli are. For example, spoken words (or any auditory stimuli) require change over time to be recognized. Kallman and Cameron (1989) have proposed that this sort of dynamic change underlies the enhanced recency effect found for auditory stimuli, relative to visual stimuli. The results of three experiments replicate and extend Kallman and Cameron's finding that dynamic visual stimuli (that is visual stimuli in which movement is necessary to identify the stimuli), relative to static visual stimuli, engender enhanced recency effects. In addition, an analysis based on individual differences is used to demonstrate that the processes underlying enhanced recency effects for auditory and dynamic visual stimuli are substantially similar. These results are discussed in the context of perceptual grouping processes. PMID- 2266866 TI - Is there a modality effect? Evidence for visual recency and suffix effects. AB - In Experiment 1, four groups of 16 subjects performed ordered recall of six syllable lists in both suffix and nonsuffix conditions. Sequential presentation of the lists varied for each group. In the auditory presentation, the syllables were delivered from one location only and were read aloud by the subjects. For the visual, spatially nondistributed presentation, the syllables appeared in one location only and were read silently. For visual, spatially distributed presentations, the syllables were spread out either vertically or horizontally and were read silently. Very robust recency and suffix effects were found in the auditory presentation, as well as in visual, spatially distributed presentations. In Experiment 2, 16 subjects performed ordered recall of visually presented lists with the items spread out vertically and conflicting spatial and temporal orders. A reliable recency effect was found for the final block of trials. In Experiment 3, 16 subjects performed ordered recall in the same conditions as in Experiment 2, except that they were instructed to recall the temporal order in which the spatial positions would be filled in. A bow-shaped curve and a strong recency effect were obtained. PMID- 2266868 TI - MDPH begins SEARCH study. PMID- 2266867 TI - MSU acquires new weapon in battle against cancer. PMID- 2266869 TI - Living wills in Michigan. Why the time is right. AB - This issue of Michigan Medicine marks a turning point in MSMS posture regarding advance directives ("living wills"). For many years, MSMS has discussed the issue and has supported legislation, more or less behind the scenes. We are now involved in a more proactive stance, trying to encourage more discussion and wider use of these devices, whether or not legislation is enacted. In this article I will: 1) review some basic terms and ethical principles; 2) recount the deliberations of the MSMS Committee on Bioethics on this topic; and 3) indicate why the time is now ripe for more action by Michigan physicians. PMID- 2266870 TI - Legal considerations of living wills. PMID- 2266871 TI - Patient capability to participate in his/her health care decisions vitally important. PMID- 2266872 TI - Physicians Recovery Network targets attitudes about impairment. PMID- 2266873 TI - DSS expands project to assist low-income persons with AIDS. PMID- 2266874 TI - Adequate documentation vital to peer review process. PMID- 2266875 TI - We need to do more things that benefit MSMS members only. PMID- 2266876 TI - Safe disposal of radioactive wastes needs physician support, direction. PMID- 2266877 TI - Women who find benign breast lump through self-exam likely to quit self-exams, U M reports. PMID- 2266878 TI - MSU uses light therapy to treat seasonal affective disorder (SAD) PMID- 2266879 TI - Increased toxin production by Vibrio cholerae O1 during survival with a green alga, Rhizoclonium fontanum, in an artificial aquatic environment. AB - In the aquatic environment, the physiological state of Vibrio cholerae can be affected by various environmental conditions (e.g., sunlight, pH, temperature, competition with other bacteria for nutrients, etc.). The effect of these factors on the toxigenicity of V. cholerae was investigated. Toxin production by 5 toxigenic strains of V. cholerae incubated in laboratory microcosms containing Rhizoclonium fontanum was tested at different time intervals. The microcosms were exposed to sunlight, and the V. cholerae were in competition for nutrients with the resident bacterial flora of R. fontanum. The increase or decrease in toxin production by V. cholerae recovered at different time intervals was measured by ELISA and compared with the parent strains. Results of the study demonstrated an increase in toxin production by V. cholerae O1 during survival with R. fontanum. It is concluded that various environmental conditions in the aquatic environment affect toxin production by V. cholerae. PMID- 2266880 TI - Linkage of ribosomal RNA genes in Leptospira. AB - We determined the linkage of 16S, 23S, and 5S rRNA genes in several strains of Leptospira and Leptonema by DNA-DNA hybridization. Almost all the hybridizations in all leptospires used in these experiments gave two radioactive bands and the results strongly suggest that the number of the 16S and the 23S rRNA genes in those strains is two, respectively. In contrast with the larger rRNAs, the number of 5S rRNA gene was different. In the strains of leptospires, L. biflexa, which were non-parasitic, there are two genes for 5S rRNA, whereas only one gene for 5S rRNA is carried in L. interrogans, which were originally isolated as parasitic. Southern hybridization experiments suggest that those rRNA genes are interspersed on the leptospiral chromosome. PMID- 2266881 TI - Effect of norspermidine and its related triamines on the cell-free polyphenylalanine synthesizing system from Vibrio parahaemolyticus. AB - The effect of norspermidine and its structurally related triamines on the cell free polyphenylalanine synthesizing system from Vibrio parahaemolyticus was examined in connection with the requirement of the system for monovalent cation. In the absence of norspermidine, the maximal incorporation of [14C]phenylalanine into hot trichloroacetic acid insoluble material was observed under ionic conditions of 12 mM Mg2+ and 50 mM NH4+. K+ could partially substitute for NH4+, but Na+ could not. The addition of norspermidine to the polyphenylalanine synthetic reaction mixture not only lowered the optimal Mg2+ concentration, but it also stimulated the polyphenylalanine synthesis up to 2-fold with no significant increase in misincorporation of [14C]leucine. Other triamines having one or two methylene chains more than norspermidine were also effective in eliciting these effects. Furthermore, Na+ could not support the polyphenylalanine synthesis even in the presence of norspermidine and, on the contrary, inhibited the polyphenylalanine synthesis induced by NH4+ regardless of whether norspermidine was present or not. These findings are discussed in comparison with the properties of other bacterial cell-free systems. PMID- 2266883 TI - Rapid small-scale preparation method of cell surface polysaccharides. AB - A rapid small-scale method of extraction of lipopolysaccharide (LPS) and capsular polysaccharides was developed for the purpose of identification of chemotypes of LPS and serotypes of capsular antigens. Cell surface polysaccharides were prepared within less than 2 hr from 1.5 ml of broth or suspension of colonies cultured overnight. The preparations were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis for LPS, and by double diffusion gel precipitation (Ouchterlony) test and blotting to nitrocellulose membrane for capsular polysaccharide. The analyses with the preparations obtained by the method could provide adequate results capable of identifying chemotypes of LPS and serotypes of capsular antigens. PMID- 2266882 TI - Characterization of gentamicin-resistant respiratory-deficient (res-) variant strains of Staphylococcus aureus. AB - Exposure of sensitive cells of Staphylococcus aureus to concentrations of gentamicin higher than the minimal inhibitory concentration, results in the recovery of low level resistant strains with a greatly altered phenotype (variants). Because the phenotypic alteration in these strains is so great the expected diagnostic characterization of these variants as S. aureus is obscured. Starting with a genetically-marked parent strain, a comprehensive cytological, physiological, morphological, genetic and biochemical analysis of the variants isolated from it was carried out. The genetic lineage of the variants to the parent was also established by DNA/DNA hybridization. Variants result from mutations in the hemin biosynthesis locus, the effect of which is to disrupt the synthesis of components of the electron transport system, lipid synthesis and selected nucleotide synthesis. Thus the strains are defective in aerobic and anaerobic respiration, (res-), in active transport of aminoglycosides (which confers low level resistance), export of characteristic exo-enzymes, and in cell wall composition and structure. PMID- 2266884 TI - Training of Kuwaiti medical doctors and their specialty choices: sociocultural impact. AB - Kuwait has a comprehensive and well-structured health care system. However, to deliver such care the country relies on expatriate medical doctors. This paper attempts to discuss the sociocultural influences on the training of Kuwaiti medical doctors and their specialty choices in order to gauge future requirements of the Kuwaiti Health Services. PMID- 2266885 TI - Mature-age entrants to medical school: a controlled study of sociodemographic characteristics, career choice and job satisfaction. AB - A comparison of 121 mature-age and 270 normal-age entrants who graduated from the University of Queensland Medical School between 1972 and 1987 shows that mature age entrants are some 7 years older, are more likely to come from public (state) schools and less likely to have parents in professional/technical occupations. Otherwise, the two groups were similar in terms of gender, marital status, number of children, ethnic background and current practice location. The educational background of mature-age entrants prior to admission includes 44.6% with degrees in health-science areas and 31.4% with degrees in non-health areas. Reasons for delayed entry of mature-age entrants include late consideration of medicine as a career (34.7%), financial problems (31.4%), dissatisfaction with previous career (30.6%), poor academic results (19.8%), or a combination of the above factors. Motivations to study medicine include family influences (more so in normal-age entrants), altruistic reasons (more so in mature-age entrants) and a variety of personal/social factors such as intellectual satisfaction, prestige and financial security (similar for both groups) and parental expectations (more so in normal age entrants). Mature-age entrants experienced greater stress throughout the medical course, especially with regard to financial difficulties, loneliness/isolation from the students and family problems (a greater proportion were married with children). While whole-course grades were similar in both groups, normal-age entrants tended to win more undergraduate honours/prizes and postgraduate diplomas/degrees, including specialist qualifications. Practice settings were similar in terms of group private practice, hospital/clinic practice or medical administration, but there was a greater proportion of mature age entrants in solo private practice, and a smaller proportion in teaching/research. If given the time over, some two-thirds of both groups would choose medicine as a career. Reasons for job satisfaction include helping patients, intellectual stimulation and financial rewards. Reasons for dissatisfaction include pressure of work, red-tape/paperwork, 'doctor-bashing', long working hours, emotional strain, financial pressure, unfulfilled career expectations and irritation with trivial medical complaints. PMID- 2266886 TI - Computer-assisted instructions: a role in teaching human gross anatomy. AB - Eight computer-assisted instructions were developed concerning selected topics in human gross anatomy. The computer lessons were designed to be very flexible in terms of the selection of material to be presented and make extensive use of colour graphics to explain the anatomy. Voluntary testing with immediate and cumulative feedback is incorporated into the lessons so that the users can evaluate their own progress in mastering the subject material. In an effort to assess the value of the computer lessons, the programs were provided to a volunteer group of 48 first-year medical students from a class of 151 students. At the completion of the gross anatomy course, the student users were requested to complete an anonymous questionnaire regarding their impressions of the value of the computer lessons. In addition, test performance on multiple choice examinations was compared between the users of the computer-assisted instructions and their non-user classmates. The responses in the questionnaires revealed a very positive attitude regarding the value and usefulness of the computer assisted instructions in learning human gross anatomy. The overall rating of the programs on a scale of 1.0 to 10.0 was 1.8 +/- 1.0 with 1.0 representing 'extremely helpful' and 10.0 being 'of no value'. A comparison of test scores showed no significant difference in test performance between the users of the computer-assisted instructions and the non-users. The results of the study suggest that while the computer lessons provide neither an advantage nor a disadvantage in test performance as evaluated by a multiple choice examination, students perceive the computer-assisted instructions as valuable educational tools in mastering the subject of human gross anatomy. The potential role of the computer-assisted instructions in curriculum development is discussed. PMID- 2266887 TI - The reliability of a hypothesis generation and testing task. AB - The purpose of this paper is to present results of initial experience with a clinical reasoning task which assesses two clearly defined aspects of clinical problem solving. Fourteen senior and 40 junior medical students at the University of Michigan Medical School participated in this study. They were given three clinical reasoning problems--the hypothesis generation and testing tasks (HG & T). As suggested by the name, two specifically defined components of clinical problem-solving, developing the initial hypotheses or differential and then testing hypotheses, were evaluated by these tasks. The findings of this study indicate that hypothesis generation and testing can be reliably evaluated with between seven and ten tasks. The results of this study suggest that reliable assessments of specific components of clinical problem-solving can be developed. PMID- 2266888 TI - Cardiology patient simulator and computer-assisted instruction technologies in bedside teaching. AB - The design and uses of an innovative technology-based approach which addresses critical problems with bedside teaching during ward rounds in the current health care situation are described. A cardiology patient simulator (HARVEY) and an accompanying computer-based interactive laserdisk system provide medical students, house officers and other health professionals with the opportunity to encounter a wide variety of clinical problems for learning and assessment. A group of cardiologists and medical educators from a consortium of US medical schools has guided the development and formal assessment of the entire system over the past 10 years. The system and simulator can be configured and programmed to provide appropriate heart sounds, laboratory data, and test results upon request; hands-on experience to practise examination skills is also available. The system, whole or in part, can be used in a variety of instructional modes from self-instruction to demonstration teaching, and from self-assessment to the final clinical examination. The system's effectiveness for teaching medical clerks is summarized, as is its use in providing continuing education for primary care doctors in rural practice. PMID- 2266889 TI - An inventory to improve clinical teaching in the general internal medicine clinic. AB - The increasing occurrence of outpatient medical care has led to the need for more and better medical education in the clinic. the Wisconsin Inventory of Clinic Teaching (WICT) was developed to improve the teaching of attending doctors in a general internal medicine clinic. The items on the inventory were derived from interviews with residents and attending doctors. The inventory was shown to have validity, and to be reliable with internal consistency correlations. We found an interesting disparity between attending doctors' and residents' expectations concerning clinical teaching. The instrument is in use as part of a teaching improvement programme for attending doctors in a general internal medicine clinic. PMID- 2266890 TI - Teaching of medical ethics. AB - Teaching medical ethics in Manchester within the introductory course of obstetrics and gynaecology is a joint activity with the Centre for Social Ethics and Policy. This interdisciplinary teaching has evolved through lecture sessions with small-group discussions dealing with topics of interest in human reproduction. The small-group discussion have been replaced by an open debate conducted by the students. Their own involvement and participation and an exposure to the disciplines of the humanities has broadened their approach to different ways of problem-solving of these real issues. PMID- 2266891 TI - The allocation of pre-registration house officer posts in the four Thames regions: a survey of house officer opinion. AB - The satisfaction of pre-registration house officers with the operation of, and outcome of participation in, their medical school's allocation scheme for house officer posts was investigated by postal questionnaire. Satisfaction with outcome was generally high. Significant differences are reported between medical schools in participation rates in allocation schemes and in satisfaction with the operation of the schemes. The operation of the ranking schemes used at Guy's and St Bartholomew's Hospitals is shown to be significantly less satisfactory. Reasons for these findings are examined. PMID- 2266892 TI - No Oscar for OSCA. AB - Structured examination methods are deservedly popular for testing component skills in medicine. Use of the methods, however, has been carried into assessment of complex performance. The note explains the inappropriateness of such use, and suggests the use of assessments based on daily clinical tasks. PMID- 2266893 TI - [The contribution of P. G. Sergiev, Sh. D. Moshkovskii and V. N. Beklemishev to the theory and practice of controlling malaria in the world]. PMID- 2266894 TI - [The utilization of the basic theoretical tenets of V. N. Beklemishev in modern biomedical science and practice]. AB - A brief review of the basic theoretical concepts of an outstanding Soviet zoologist V. N. Beklemishev in the field of parasitology, general epidemiology, medical entomology, theory of evolution is presented. The influence of Beklemishev's theoretical concepts on modern science and practice is discussed, prospects for the use and development of those concepts are reviewed. PMID- 2266895 TI - [The status and tasks of the training of parasitologists in the USSR]. AB - Modern state of under- and postgraduate training of medical parasitologists is reviewed. Main tasks for the improvement of specialist training have been outlined, in particular due to the fact that the educational institutions will work on a self-accounting principle in the nearest future. PMID- 2266896 TI - [A new approach to overcoming the drug resistance of the causative agents of malaria]. AB - Progressively expanding area of multiresistant falciparum malaria and the profile of its resistance to drugs successively implemented into practice necessitate the elaboration of approaches to the "revival" of the drugs used. As with neoplastic cells, a correlation between plasmodium multiresistance with increased "outflow" of specific drugs from the cell is suggested, which is blocked by inhibition of Ca2+ transport. Reversion of resistance to chloroquine by a combination with Ca2+ channel blockers verapamil, tricyclic antidepressants (desipramine, protritreline, etc.), tricyclic antihistamine drugs (cyproheptadine), and reversion of resistance to sulfadoxine in combination with the antihistamine drug ketodiphene have been shown in vivo and in vitro. The function of Ca2+ channels is directly related to Ca2(+)-, Mg2(+)-dependent ATPase. Ph-metric techniques elaborated in the USSR make it possible to evaluate its activity, determine the inhibitors, differentiate them according to the effect. The authors have established reversion of P. berghei resistance to chloroquine, with the tricyclic antidepressants azaphen, aminazin, triftazin correlating with the degree of Ca2+, Mg2(+)-ATPase inhibition and to praziquantel, whose effect might be associated with the increased permeability of the cellular membrane to Ca2+. The inhibitors of Ca2+ transport have various parasitocidal activities which might be accounted for by the deficiency of this cation necessary for plasmodium development. The task is to elaborate safe optimum antimalarial drug/modulator of Ca2+ transport combinations. Multiresistance (genetically predetermined multifactorial cellular changes) may be associated with enhanced synthesis of transmembrane glycoprotein with varying molecular mass depending on the direction of resistance. PMID- 2266897 TI - [The biological aspects of the therapy of parasitic diseases]. AB - Specific drugs, most of them heterocyclic compounds, are leading in the therapy of parasitic infections despite their relative toxicity and potent mutagenicity. In some parasitic diseases chemotherapy is of low efficacy (hydatid and multilocular echinococcosis, African trypanosomiasis) or practically absent (American trypanosomiasis) mostly due to suppression or distortion of an immune response. Methods of immunocorrection using recombinant cytokines (interleukins, interferons) or their inducers are to be borrowed from the practice of treatment of oncological, lymphoproliferative diseases and other immune deficiencies. For instance, alpha-interferon and gamma-interferon inducers should be used in echinococcosis, where, as our studies have shown, the production of these cytokines is markedly suppressed. The enforcement of chemotherapeutic effect by "parachemotherapy" (Sh. D. Moshkovskii, 1944), the effect of nonspecific pharmacological drugs upon the cells and tissues damaged by parasites (like Ca2+ transport blockers in drug-resistant falciparum malaria), should be used, for instance, recombinant gamma-interferon plus specific drugs in toxoplasmosis. Modern methods of immunotherapy based on the molecular mechanisms of a host parasite relationship should be created, for instance, monoclonal antibodies to C3 receptors of membranes of cells invaded with Toxoplasma gondii. Immunotoxins such as monoclonal antibodies to myoblast receptors conjugated to 5 nitroimidazolyl-thiadiazole in Chagas' disease should be tested. The above mentioned biological approaches should increase the efficacy of chemotherapy in parasitic diseases with smaller amounts of specific drugs and less courses of treatment. PMID- 2266898 TI - [The outlook for the development of the immunodiagnostic and immunoprophylactic trends in parasitology]. AB - The current state of immunodiagnostic and immunopreventive trends in parasitology and prospects for their development are analysed. The prospects of immunodiagnosis seem to be in increased sensitivity and specificity of tests by improving the methods and using the achievements of biotechnology in the manufacturing of high quality antigenic and antibody reagents. The development of immunoprevention of parasitoses can be stimulated by further studies of the mechanisms of a protective immune response, ways of its enhancement, search for natural and design of synthetic protective antigens and elaboration of new methods of their biological transport. The importance of the studies of local immunity phenomena is stressed for the development of new effective methods of immunodiagnosis and immunoprevention of socially valuable human parasitoses. PMID- 2266899 TI - [The 70th anniversary of the E. I. Martsinovskii Institute of Medical Parasitology and Tropical Medicine of the Order of the Red Banner of Labor of the Ministry of Public Health of the USSR (pages from its history)]. PMID- 2266900 TI - [Achievements in the search for and creation of Soviet anthelmintic agents]. AB - Basic achievements in the creation of antinematodal, anticestodal and antitrematodal agents are reviewed chronologically. It is shown that the search was performed mainly among the derivatives of benzimidazole, cyclic amidines, diphenylmethane, salicyl anilides, pyrazine isoquinolines, among natural products of avermictines and milbemicines. It is noted that nowadays there is every possibility for the treatment of mass helminthiases in the USSR. However, it has been found that some drugs are associated with a certain risk and therefore the necessity for further search of safe anthelminthic agents has been emphasized. PMID- 2266902 TI - [New aspects of the epidemiology of tick-borne encephalitis]. AB - Profound studies of the mechanisms of virus transfer by bites and the behaviour of the infected ticks of male Ixodes ticks in the virus transfer and establish the effect of early and short-term suction of ticks in the onset of the disease. Preservation of saliva cement stopper in the skin of the infected vertebral host is of particular importance in the epidemiology and epizootiology of tick-borne encephalitis, as the cement cone in the skin may contain the quantity of the virus comparable with its concentration in the whole body of the tick. The experimental data suggest the predominant and more successful virus multiplication in the most viable and active ticks of the population as well as virus-induced stimulation of searching activity in the infected ticks. The attention is attracted to possible retention of the natural virus store by its elimination with the saliva of male ticks and virus exchange by sucking of the infected saliva from the affected focus on the skin by noninfected ticks fed together with infected insects, insensitive to tick-borne encephalitis virus. PMID- 2266901 TI - [The practical utilization of helminthological health research]. AB - The article stresses the necessity of the implementation of the achievements in the field of sanitary helminthology into the practice of medical institutions. Recommendations are given on increasing the efficacy of marking helminths' oocytes on various objects, on the disinfection of sewage and soil. The implementation of the above achievements and recommendations into practice will make it possible to rule out the role of environmental objects in the epidemiology of helminthiases and to enhance the efficacy of anthelminthic measures. PMID- 2266903 TI - [The degree of coincidence of the long-term extrapolated expert prognosis with the real morbidity of tick-borne encephalitis in the USSR]. AB - Tick-borne encephalitis morbidity over the period of 1952-1981 was assessed and the prognosis was made for 29 administrative territories for the 1980s and early 1990s. The changes in the morbidity in 1982-1988 have shown the coincidence with the prognosis in 70% of cases, in 20% of cases stability was noted instead of the predicted growth or drop in the morbidity, in 10% of cases real changes were contrary to the predicted ones. The peak of the disease onset was predicted correctly on 16 out of 22 territories, in 3 cases peak of the disease was observed 2 years earlier, in 1 case it was noted 4 and in 1 case 8 years earlier. Measures for improvement of the quality of the prognosis are suggested. PMID- 2266904 TI - [The isoenzyme identification and pathogenic characteristics of the Leishmania isolated in natural foci of cutaneous leishmaniasis in the USSR]. AB - By 8-11 enzymes, using polyacrylamide gel electrophoresis, 378 isolates from R. opimus, 3 isolates from M. libycus, 4 isolates from P. andrejevi, 1 isolate from P. papatasi, 1 isolate from S. murgabiensis and 25 isolates from human patients with skin leishmaniasis have been identified. Using starch gel electrophoresis, 17 strains from R. opimus and 3 strains from patients have been additionally identified by 12 enzymes. All the isolates were tested for ability to cause leishmaniasis disturbances in golden hamsters intracutaneously injected into the ear. It is established that L. major is a polytypic group which on the territory of the USSR consists of 3 independent species: L. major (in a narrower sense), L. gerbilli and L. sp. nov, a new earlier unknown species. All three types of Leishmania are specific parasites of R. opimus and only L. major may affect man and M. libycus. 3 types of Leishmania may coexist in the body of one animal. In R. opimus and golden hamsters, all of them caused only skin damages, visceralization was never registered. In golden hamsters, L. major always caused progressing ulcers, while L. sp. nov. and L. gerbilli caused only infiltrative damages. Only 9 (3%) of 268 L. sp. nov. isolates caused ulcers developing similar to those caused by L. major in the experimental animals. The data obtained account for the local nature and seasonal regularities of the epidemic process in the natural foci of skin leishmaniasis by the changing proportion of L. major in the complex of Leishmania encountered in R. opimus. PMID- 2266905 TI - [The differentiation of Opisthorchis eggs by the ultrastructure of their outer membranes]. AB - Using a TESLA-BS-300 scanning electron microscope, the ultrastructure of the outer membranes of oocysts of 8 opisthorchis species (Opisthorchis felineus, O. viverrini, O. geminus, Clonorchis sinesis, Amphimerus anatis, Metorchis albidus, Pseudamphistomum truncatum, Erchoviorchis lintoni) belonging to 4 subfamilies, as well as that of O. felineus oocysts of various geographical isolates (from the Ukraine, the Volga region, West Siberia, Kazakhstan) have been investigated. The nature of the ultrastructure of the membranes differs from species to species and can be used for the differentiation of opisthorchis oocysts. Marked differences have been observed in different opisthorchis subfamilies (Opisthorchinae, Metorchinae, Pseudamphistominae, Pseudamphimerinae). The membrane ultrastructure was not significantly different in O. felineus oocysts from various geographical isolates, however, there are some distinctions in the size of oocysts and the form of apical thorns and opercular endings. The work has been done within the framework of the international scientific cooperation between the E. I. Martsinovskii Institute of Medical Parasitology and Tropical Medicine, USSR Ministry of Public Health and the Institute of Parasitology, the Czechoslovakian Academy of Sciences. PMID- 2266906 TI - [Approaches to predicting the diphyllobothriasis and opisthorchiasis situation in connection with the reconstruction of the water supply economy in the USSR]. AB - The effect of some physical-geographical and anthropogenic factors on the circulation of Diphyllobothriidae and Opisthorchis at the hydrotechnical objects of various regions of the USSR is analysed. It is emphasized that these factors affect primarily the first intermediate hosts of parasites. In opisthorchiasis changes in the intensity of the epidemic process may take place within the limits of mollusca distribution area. In diphyllobothriasis, the area of distribution may be expanded and new foci may be formed with the changes in the river hydroregimen. PMID- 2266907 TI - [An assessment of the clinical status of patients with alveolar echinococcosis by using statistical processing methods. 1. An assessment of the stage of the disease by cluster analysis]. AB - The clinical condition was assessed in 44 patients with alveolar echinococcosis, using methods of mathematical analysis of 10 basic routine laboratory parameters reflecting protein-forming liver function and immune disturbances. The data were processed on a "NOVA-2" [correction of "HOBA-2"] computer using Fortran software on taxonomy 7 classes of conditions were determined, which reflect the progressing severity of the pathological process and correspond to three stages of the disease: uncomplicated, complicated and terminal. A high clinical value of the method has been demonstrated for the evaluation of the patient's condition and determination of the treatment tactics as well as its importance for the creation of a clinical data bank in the invasion focus. PMID- 2266908 TI - [The clinical efficacy of and tolerance for lariam (mefloquine) in tropical malaria in the south of the Socialist Republic of Vietnam]. AB - The study was performed in the area of distribution of tropical malaria resistant to 4-aminoquinolines (Vietnam) on 30 patients receiving lariam (mefloquine). The results were compared to the standard therapy with quinine and fansidar. They indicate a high efficacy of and a good tolerance to the drug tested. The use of lariam leads to a more rapid (as compared to the standard treatment) elimination of parasitemia and complete eradication of the disease relapses. The findings make it possible to recommend lariam for the prevention and treatment of tropical malaria. PMID- 2266910 TI - [Petr Grigor'evich Sergiev--the director of the E. I. Martsinovskii Institute of Medical Parasitology and Tropical Medicine of the Ministry of Public Health of the USSR]. PMID- 2266909 TI - [The modelling of the multiple drug resistance of the malarial parasites. 1. The combined resistance of Plasmodium berghei to chloroquine and fansidar]. AB - Using a recurrent technique, P. berghei isolate resistant to chloroquine-fansidar combination is formed in golden hamsters. The isolate resistant to chloroquine fansidar combination was 4 times less sensitive to chloroquine, 2 times less sensitive to fansidar and its combinations, 2 times less sensitive to sulfadoxine, 31 times less sensitive to pyrimethamine, as compared to the baseline isolate LNK65 P. berghei characterized by naturally reduced sensitivity to chloroquine. PMID- 2266911 TI - [Cardiac findings in alcoholic liver disease]. AB - In a prospective study 53 patients with alcohol-induced liver disease (fatty liver in 27, cirrhosis in 26) were studied clinically and with non-invasive techniques (electrocardiogram, systolic time intervals, M-mode echocardiography, upright bicycle stress test) to detect a possible cardiac involvement. Mean daily alcohol consumption was comparable in both groups (136 g/day over 16 years vs 124 g/day over 14 years). 15 to 41% of patients (more patients with fatty liver) complaint of angina pectoris and dyspnea at exercise or had palpitations. Echocardiography and systolic time intervals demonstrated in both groups (in patients with cirrhosis despite of a more intensive therapy with digitalis and diuretics) a marked enlargement of left ventricular dimensions with a significant (p less than 0.05) degree of dysfunction (PEP/LVET). Electrocardiography showed abnormalities in 26 to 44% of patients: signs of right ventricular enlargement in 26% of patients with fatty liver, and a prolongation of myocardial repolarisation (QTc) in 44% of patients with cirrhosis. Patients with alcohol-induced liver disease deserve more attention of their cardiac complaints, clinical and functional findings. PMID- 2266912 TI - [Long-term results following kidney transplantation. An empirical analysis of 467 allogeneic kidney transplants concerning the effect of clinical and immunological variables on graft function]. AB - In a homogeneous group of 467 cadaver kidney transplants performed within one single center between 1979 and 1987, we analysed the influence of main risk factors on long-term survival up to 72 months. Calculating survival rates by Kaplan-Meier actuarial methods the overall graft survival exceeded 71%. The corresponding patient survival was higher than 90%. A good HLA-A-B and DR match was of significant positive influence. Patients who received cyclosporine had a significant better outcome compared to conventional immunosuppressive therapy. A marked advantage was demonstrated for such variables as number of pretransplant blood transfusions, number of rejection episodes, preservation time and renal function as measured by plasma creatinine. Independently age was a main risk factor for curtailed graft survival. Although immunological factors accounted for more than 45% of transplant loss we found a surprisingly high percentage of infections (36%). Vascular problems or technical failure were below 10%. We conclude that a profound clinical examination in the pretransplant period is of high value and remains necessary to identify high risk patients in the long range. PMID- 2266914 TI - [Recombinant interferon alpha-2A in the treatment of HIV-associated Kaposi sarcoma. Long-term results]. AB - 47 HIV-positive male patients with cutaneous Kaposi's sarcoma (KS) were treated with recombinant interferon alpha-2A (IFN) in an open, prospective study. 45 patients received 18 million I.U. IFN s.c. daily for the first three months. From the fourth month, the patients received 18 million I.U. IFN s.c. three times weekly. Four of the 45 patients withdrew from therapy because of side effects during the first weeks (weeks 2 to 6) of treatment. The remaining 41 patients were treated for a minimum period of two years or until their death. Two further patients received 36 million I.U. IFN daily for three months. After three months of IFN therapy we observed complete remission (CR) in five of the 41 patients (12%), partial remission (PR) in seven patients (17%), stable disease in seven patients (17%) and progressive disease (PD) in 22 patients (54%). The mean survival time from the beginning of IFN therapy to date is 26 months for the 19 responders (patients with CR, PR or SD; six are still alive) and nine months for the 22 non-responders (patients with PD; all died). Recurrence of tumor progression occurred in 15 of the 19 responders after an average of ten months of continuous IFN therapy. The longest time of survival in this group is 54 months up to now. Of the four remaining patients, all in the CR group, two died after 24 and 26 months of IFN therapy, without any recurrence of KS growth (causes of death: Burkitt's lymphoma and unknown). The two other patients, both still alive, have not suffered any recurrence of tumor progression after 40 and 41 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266913 TI - [Improved prognosis of Type I and Type II diabetics with nephropathy]. AB - Between 1966 and 1985, 72 type I and 75 type II diabetics developed persistent proteinuria. These patients were divided into two groups according to time of onset of proteinuria (1966 to 1975 and 1976 to 1985, respectively). In these groups, we investigated both the quality of antihypertensive treatment and metabolic control as well as the course of nephropathy and life prognosis. Control of hypertension was markedly improved in type I and type II diabetics with later onset of proteinuria (1976 to 1985), compared with patients who developed proteinuria between 1966 and 1975. However, metabolic control was improved only in type I diabetics. Compared with the previous decade, prevalence of renal insufficiency was lowered by one-third in type I and type II diabetics with later onset of proteinuria (1976 to 1985). During the six-year observation period, 32% of type I and 72% of type II diabetics who developed proteinuria between 1966 and 1975 died, whereas all type I and 54% of type II diabetics with later onset of proteinuria (1976 to 1985) survived. The study shows that conservative treatment methods, especially lowering of blood pressure, may improve prognosis for proteinuric type I and type II diabetic patients. PMID- 2266915 TI - [Cervical lymph node swelling and diarrhea. Freiburger gastroenterology discussion]. PMID- 2266916 TI - [Symptoms, therapy and prognosis of spontaneous esophagus rupture (Boerhaave syndrome)]. PMID- 2266917 TI - [Current trends in the therapy of respiratory tract infections]. PMID- 2266918 TI - [Tasks and meaning of the ethics commission]. PMID- 2266919 TI - [Lung tuberculosis with extensive mouth and bronchial mucosa involvement in a non immunocompromised 52-year-old female patient]. PMID- 2266920 TI - [Endoscopic polypectomy in one or two times?]. PMID- 2266921 TI - Volume performance standards: can they control growth in Medicare services? AB - Congress has adopted volume performance standards (VPSs), a system using collective incentives, as a means to control costs of physicians' services under the Medicare program. Past efforts to curb expenditures failed to focus sufficiently on providing direct incentives to individual providers or consumers, and did not achieve desirable results. West German and Canadian experiences suggest that mechanisms to contain costs may work best when their scope is regional rather than national, prompting the view that the VPS system should operate on a state level. The system's efficacy may also require Medicare officials to analyze utilization patterns assiduously, and states' medical and professional organizations to monitor physicians' practices and formulate due practice guidelines. PMID- 2266922 TI - HIV and childbearing.1. Uncertain risks and bitter realities: the reproductive choices of HIV-infected women. AB - Although most babies born to women with HIV will not develop AIDS, many health professionals and segments of the public object when these women will not forgo pregnancy. Such a view fails to consider fully the cultural, political, and socioeconomic contexts in which seropositive women make reproductive choices. HIV infection is only one of many conditions of chronic disease that can be passed from a woman to her fetus, and should not be singled out as a target for coercive policies. Rather, government and society have an obligation to empower women to protect themselves against HIV infection in the first place, and to offer them options for self-esteem and achievement independent of reproduction. PMID- 2266923 TI - HIV and childbearing. 2. AIDS and reproductive decisions: having children in fear and trembling. AB - The risks of perinatal HIV transmission do not currently constitute grounds for morally criticizing the reproductive choices of particular infected women. A contextualized assessment of morally relevant factors might in some cases, however, justify judgments of reproductive irresponsibility. Although no women should be subject to any form of coercive pressure when making the decision to initiate or continue pregnancy, a "moral-education" model of nondirective counseling may be appropriate for women carrying HIV. Not even highly desirable, concerted public efforts to foster social justice will eliminate the ethical questions of whether these women should have children and how to counsel them. PMID- 2266924 TI - Age, socioeconomic status, and health. AB - Analysts dispute what roles biomedical, psychosocial, and other factors play in determining the duration of morbidity and disability over the life course. Cross sectional data from two national surveys of adults aged 25 years and over not only show, however, that age and socioeconomic status (SES) are significant predictors of self-reported physical health; they also demonstrate that the relation of age to health varies with SES features. Longitudinal research is needed to test the finding that enduring functional limitations in terms of time are actually compressed in higher SES groups. To improve well-being in our society, moreover, requires specifying why SES differences occur, and perhaps ultimately reducing socioeconomic inequality itself. PMID- 2266925 TI - Assessing and assuring the quality of home health care: a conceptual framework. AB - Increased use of home care services, and the provision of more sophisticated care to acutely ill patients, have prompted concern about quality assurance in home settings. A conceptual framework is proposed to assess home health-care quality based on two premises: outcome, process, and structural measures, first, are required to evaluate quality accurately; classification of patients into quality indicator groups (QUIGs), second, permits specification and use of more practical and valid quality measures. The framework may prove useful because measures are related directly to patient conditions, services rendered, and treatment objectives. Further reliability and validity testing of the QUIGs and a system of operational quality measures are currently underway. PMID- 2266927 TI - It's just not cricket! PMID- 2266926 TI - Mentoring works for both sides. PMID- 2266928 TI - Nurse Education Tomorrow Conference 1990. How nurses learn and how to improve the learning environment. AB - This paper considers some of the evidence that can help nurse teachers more effectively prepare nurses for practice. In particular it is concerned with how students learn and how teachers can improve the learning environment. There are four main sections to the paper. The first looks at learning styles and considers the importance of matching teaching style to the learning style of the student. The second section considers the research into the process of integrating theory and practice in nursing education and the relationship between theory, the classroom and the clinical area. The next section of the paper looks at factors influencing the process of becoming a nurse. Socialising agents such as people and techniques are reviewed in the light of research evidence from nursing and similar professions. Finally the paper represents a series of ways in which it is possible to assess and improve the learning environment for the student nurse, including human aspects, equipment and information. PMID- 2266929 TI - Faculty evaluation: a closer look at peer evaluation. AB - As long as there have been academic institutions, administrators, faculty, and students, there have been evaluations. Evaluation involves placing a value or making a judgement about some aspect(s) of performance. Evaluation in nursing education has been studied extensively with respect to nursing students' academic and clinical performance. However, it is only in the last 2 decades that the issue of faculty evaluation has gained increased attention. Trends in nursing education with respect to the development of the overall concept and sources of input for evaluation of the nurse educator are discussed in this paper. Specific attention is focused on the process of peer evaluation and a tool to facilitate the peer evaluation process is included. PMID- 2266930 TI - The case study approach of teaching decision-making to post-diploma nurses. AB - This paper discusses the value of using a case study approach to teaching decision-making in a post-diploma baccalaureate degree nursing program. Given specific cases, students analyse how decisions are derived and are encouraged to look at the processes used rather than only on the product generated. In this way, the perception that there is only one correct approach is downplayed while students explore several creative solutions to simple and complex nursing situations. The case study method draws on the students' experiential, intuitive, and knowledge bases through sharing and discussion, thereby enhancing comprehensive learning. A broader perspective of decision-making is fostered and integration of critical thinking skills is facilitated. PMID- 2266931 TI - From educational philosophy to educational practice: fidelity and the curriculum in context. AB - As part of a higher degree on research methods, exploratory work was undertaken concerning educational philosophy and educational practice using an ethnographic approach. This author discusses, using this exploratory work, the difficulties of attempting fidelity to an educational philosophy, through curriculum practice. Schools of nursing are increasingly adopting a rational approach to education, without considering the wider social context within which education occurs. The attempt to establish and pursue a single philosophy, ignores the plurality of ideological commitments held by nurse teachers. Further research is proposed using naturalistic methods in order to understand the processes of interpretation and implementation of educational philosophy. PMID- 2266933 TI - School nurses and health education for pupils with and without intellectual handicaps: a study conducted in Japan and Sweden. AB - The purpose of this study is to report the results from a questionnaire that was given to about 600 school nurses working in schools which have pupils with and without intellectual handicaps in Japan and Sweden, concerning their opinions on health education including sex and interpersonal relationships. The study was conducted during the spring 1987 in Sweden and during the autumn 1987 in Japan. The main results from this study concern differences between Japanese and Swedish school nurses when answering certain questions. These questions, for instance, concerned the nurses' working situation and their health education for pupils with and without intellectual handicaps. Of all the Japanese school nurses 27%, compared to 90% of the Swedish school nurses, taught about health including sex and interpersonal relationships in regular classes. Of school nurses having pupils with intellectual handicaps, only 1% of the Japanese school nurses, compared to 47% of the Swedish school nurses, taught their pupils these subjects. These differences merely seemed to be related to the educational system, including its curriculum, reflecting the general policy held within each country. PMID- 2266932 TI - Evaluating the impact of continual professional education (ENB 941). AB - It is often assumed that participation in continuing professional education (CPE) activities necessarily results in maintenance of competence and improvements in nursing practice. A literature review revealed that evaluation of CPE activities is frequently limited to the completion of forms at the conclusion of the offering, indicating the extent to which the objectives have been achieved and the general level of satisfaction of the participants. Very little attention seems to have been paid to the longer term effects of the CPE activity on the individual participant or on their ability to provide an enhanced level of nursing practice--the raison d'etre of CPE. This project was designed to explore the impact of ENB 941 on course participants. A group of 11 nurses and their six clinical managers were interviewed 10 months following course completion to discuss the effects of the course on the professional, educational and individual development of course participants and on their ability to improve nursing practice. Analysis of the interviews suggests that all group members used some of the opportunities available in the course to further their development. All clinical managers agreed that despite staffing and financial implications, the course provided value for money in terms of staff development and enhanced nursing practice. PMID- 2266935 TI - Didactic psychodrama and sociodrama. AB - The terms psychodrama, sociodrama, and didactic psychodrama are defined. These three action techniques are compared with respect to their differing goals and methodologies. The application of the use of didactic psychodrama and sociodrama with student nurses undergoing Psychiatric Nurse Training is outlined, together with verbal reports elicited from the students following, a) a 20-week study day programme where didactic psychodrama was used on an regular basis, and b) a sociodrama workshop. It is concluded that sociodrama and didactic psychodrama are powerful action learning methods that can be successfully employed with junior student psychiatric nurses. It is also acknowledged that the underlying rationale, and procedural details of these two methods differ from, those associated with more conventional social skills based training approaches, and these differences have implications for trainers. PMID- 2266934 TI - University validation of Project 2000 courses. AB - The need for academic validation of Project 2000 courses has implications for schools/colleges who intend to offer such courses. These include not only academic aspects of the course curriculum, but also the development of students and the need for joint validation. In this paper, these aspects are discussed from the particular perspective of university accreditation, but it is probable that most of the issues raised will be relevant irrespective of the validating body. The issues will have been the concern of nurse educators in the past, and the intention here is to place these issues in the context of academic validation. The paper is based on the writers' experience of taking part in the validation of such a course, as a university lecturer who has also worked in a school of nursing. PMID- 2266936 TI - Post-graduate initiatives in pre-registration nursing education: a case study in curriculum development. AB - The authors traces the development of plans to provide special schemes of training for graduate recruits to a Project 2000 course. The plans are shown to be founded in earlier curriculum development associated with the 1982 syllabus for mental nursing. PMID- 2266937 TI - Empowerment through a professional organization: the experience of Latvian nurses. PMID- 2266938 TI - Integration of Agrobacterium T-DNA into a tobacco chromosome: possible involvement of DNA homology between T-DNA and plant DNA. AB - We established tobacco tumour cell lines from crown galls induced by Agrobacterium. Restriction fragments containing T-DNA/plant DNA junctions were cloned from one of the cell lines, which has a single copy of the T-DNA in a unique region of its genome. We also isolated a DNA fragment that contained the integration target site from nontransformed tobacco cells. Nucleotide sequence analyses showed that the right and left breakpoints of the T-DNA mapped ca. 7.3 kb internal to the right 25 bp border and ca. 350 bp internal to the left border respectively. When the nucleotide sequences around these breakpoints were compared with the sequence of the target, significant homology was seen between the region adjacent to the integration target site and both external regions of the T-DNA breakpoints. In addition, a short stretch of plant DNA in the vicinity of the integration site was deleted. This deletion seems to have been promoted by homologous recombination between short repeated sequences that were present on both sides of the deleted stretch. Minor rearrangements, which included base substitutions, insertions and deletions, also took place around the integration site in the plant DNA. These results, together with previously reported results showing that in some cases sequences homologous to those in T-DNA are present in plant DNA regions adjacent to left recombinational junctions, indicate that sequence homology between the incoming T-DNA and the plant chromosomal DNA has an important function in T-DNA integration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266939 TI - Multiple interactions between tissue-specific nuclear proteins and the promoter of the phosphoenolpyruvate carboxylase gene for C4 photosynthesis in Zea mays. AB - The expression of the phosphoenolpyruvate carboxylase (PEPC) gene involved in C4 photosynthesis is regulated in a highly organized manner. Nuclear factors interacting with DNA fragments from the 5' flanking region (from positions -1012 to +88 relative to the transcription start site) of the maize gene were identified by gel shift assays. Among the three kinds of such nuclear proteins (MNF1, MNF2a and MNF2b) found in the extract from maize leaves, MNF2a and MNF2b, which were distinguishable by their chromatographic behavior, interacted with the same motif of the repeated sequence (RS2) in the region from -432 to -201. MNF1 interacted with the region from -905 to -818 in which two copies of another kind of repeated sequence (RS1) reside. All of these nuclear factors were found only in the extracts from green and etiolated leaves but not in those from stems and roots. The relative content of MNF1 and MNF2b was almost equal in green and etiolated leaves, while that of MNF2a was significantly higher in etiolated leaves than green leaves. It is suggested that expression of the PEPC gene is controlled by the combined effects of these nuclear factors. PMID- 2266940 TI - Cloning and sequencing of cDNAs encoding two self-incompatibility associated proteins in Solanum chacoense. AB - We have isolated and sequenced cDNAs for S2- and S3-alleles of the self incompatibility locus (S-locus) in Solanum chacoense Bitt., a wild potato species displaying gametophytic self-incompatibility. The S2- and S3-alleles encode pistil-specific proteins of 30 kDa and 31 kDa, respectively, which were previously identified based on cosegregation with their respective alleles in genetic crosses. The amino acid sequence homology between the S2- and S3-proteins is 41.5%. This high degree of sequence variability between alleles is a distinctive feature of the S-gene system. Of the 31 amino acid residues which were previously found to be conserved among three Nicotiana alata S-proteins (S2, S3, and S6) and two fungal ribonucleases (RNase T2 and RNase Rh), 27 are also conserved in the S2- and S3-proteins of S. chacoense. These residues include two histidines implicated in the active site of the RNase T2, six cysteines, four of which form disulfide bonds in RNase T2, and hydrophobic residues which might form the core structure of the protein. The finding that these residues are conserved among S-proteins with very divergent sequences suggests a functional role for the ribonuclease activity of the S-protein in gametophytic self-incompatibility. PMID- 2266941 TI - Direct screening of a small genome: estimation of the magnitude of plant gene expression changes during adaptation to high salt. AB - Mesembryanthemum crystallinum (common ice plant), a facultative halophyte with a genome size of 393,000 kb, was used to estimate the magnitude of changes in gene expression in response to environmental stress by excess salt. Such treatment induces a water-conserving pathway of carbon assimilation (CAM) which is, at least in part, transcriptionally controlled. From a genomic library, 200 phage containing approximately 3200 kb (0.8% of the genome) were randomly selected. The inserts in these clones could be divided into four classes ranging from highly repetitive DNA (class I clones) to single-copy DNA (class IV clones). The inserts of the 166 clones of classes II to IV were digested with various restriction enzymes and the fragments were analyzed by hybridization with radioactively labelled mRNA isolated from stressed and unstressed leaves. We found that a total of approximately 140 DNA fragments hybridized with the RNA probe. Among those, several differentially regulated transcripts were observed. Stress-dependent fluctuation of mRNA abundance was verified by Northern analyses: one mRNA, not detectable in unstressed leaves, appeared in stressed leaves, while steady-state levels of three transcripts decreased during stress. All regulated signals are derived from low abundance mRNAs, which may be missed during screening of cDNA libraries. We conclude from these results that, for the entire genome, on the order of more than one hundred genes are differentially regulated in response to salt stress. PMID- 2266942 TI - A transcript identified by MuA of maize is associated with Mutator activity. AB - A Mu element, which we designated MuA, was cloned from a maize line with a Mutator background by its homology to the terminal inverted repeats of Mu1. Like other Mu elements, MuA has terminal inverted repeats of approximately 200 bp which are homologous to those of Mu1, but the internal region is different. MuA is unique in several aspects, being approximately 5.5 kb in size and the largest Mu element reported to date. It is flanked by 8 bp duplications instead of the 9 bp duplications found in most other Mu insertions. The internal sequences of MuA hybridize to restriction fragments that cosegregate with Mutator activity in maize lines showing 1:1 segregation for somatic mutability. The most interesting observation is that a transcript of approximately 3.5 kb identified by the internal sequences of MuA is both qualitatively and quantitatively associated with Mutator activity. This transcript is present in maize lines containing germinal Mutator activity but is undetectable in maize inbreds with no known Mutator activity. The amount of the transcript is decreased in lines that have lost germinal Mutator activity. Northern analysis of maize a1-Mum mutant lines that segregate 1:1 for mutability shows that a transcript of the same size is associated with somatic Mutator activity. These data suggest that the 3.5 kb transcript is produced by the autonomous element that confers both germinal and somatic Mutator activity. The possibility that MuA is an autonomous or regulator element of the Mu family is discussed. PMID- 2266943 TI - The VANA glycopeptide resistance protein is related to D-alanyl-D-alanine ligase cell wall biosynthesis enzymes. AB - Inducible resistance to the glycopeptide antibiotics vancomycin and teicoplanin is mediated by plasmid pIP816 in Enterococcus faecium strain BM4147. Vancomycin induced the synthesis of a ca. 40 kDa membrane-associated protein designated VANA. The resistance protein was partially purified and its N-terminal sequence was determined. A 1761 bp DNA restriction fragment of pIP816 was cloned into Escherichia coli and sequenced. When expressed in E. coli, this fragment encoded a ca. 40 kDa protein that comigrated with VANA from enterococcal membrane fractions. The ATG translation initiation codon for VANA specified the methionine present at the N-terminus of the protein indicating the absence of signal peptide processing. The amino acid sequence deduced from the sequence of the vanA gene consisted of 343 amino acids giving a protein with a calculated Mr of 37,400. VANA was structurally related to the D-alanyl-D-alanine (D-ala-D-ala) ligases of Salmonella typhimurium (36% amino acid identity) and of E. coli (28%). The vanA gene was able to transcomplement an E. coli mutant with thermosensitive D-ala-D ala ligase activity. Thus, the inducible resistance protein VANA was structurally and functionally related to cytoplasmic enzymes that synthesize the target of glycopeptide antibiotics. Based on these observations we discuss the possibility that resistance is due to modification of the glycopeptide target. PMID- 2266944 TI - Species-specific RNA editing patterns in the mitochondrial rps13 transcripts of Oenothera and Daucus. AB - Transcripts from the rps13 locus, which encodes ribosomal protein S13, in Oenothera and Daucus mitochondria are edited by several cytidine to uridine transitions in both plants. Analysis of individual cDNA clones and polymerase chain reaction (PCR)-amplified cDNA from the total mitochondrial mRNA population shows different editing patterns in the two species. Although the same genomic triplet is conserved, nucleotides altered in the mRNA of one species are not necessarily edited in the other. Individual editing sites appear to be modified to varying degrees in the mRNA populations in both plant species, indicating that completely edited transcripts constitute only a minor fraction of the rps13 mRNA molecules. PMID- 2266945 TI - The nifEN genes participating in FeMo cofactor biosynthesis and genes encoding dinitrogenase are part of the same operon in Bradyrhizobium species. AB - The nucleotide sequences of genes homologous to the Klebsiella pneumoniae nifEN genes have been determined in Bradyrhizobium japonicum 110. The coding regions for the nifE and nifN consist, respectively, of 1641 and 1407 nucleotides. The nifD gene (coding for the beta-subunit of dinitrogenase) and nifE are linked, and separated by 95 nucleotides. In the region of 12 nucleotides that separates nifE from nifN the stop codon for nifE overlaps the putative ribosome binding site for nifN. In contrast to Klebsiella and Azotobacter vinelandii, the B. japonicum nifEN genes are linked to the nifDK genes in the same operon. Comparison of dinitrogenase polypeptides (nifDK products) and the polypeptides of the nifE and nifN genes reveals considerable homology between nifD and nifE, and between nifK and nifN. Several protein domains, containing highly conserved cysteine residues, are conserved among the gene products of nifD, nifK, nifE and nifN. This result allows us to propose a probable evolutionary pathway for the common origin of these genes. PMID- 2266946 TI - Analysis of a cDNA encoding arginine decarboxylase from oat reveals similarity to the Escherichia coli arginine decarboxylase and evidence of protein processing. AB - Arginine decarboxylase is the first enzyme in one of the two pathways of putrescine synthesis in plants. We purified arginine decarboxylase from oat leaves, obtained N-terminal amino acid sequence, and then used this information to isolate a cDNA encoding oat arginine decarboxylase. Comparison of the derived amino acid sequence with that of the arginine decarboxylase gene from Escherichia coli reveals several regions of sequence similarity which may play a role in enzyme function. The open reading frame (ORF) in the oat cDNA encodes a 66 kDa protein, but the arginine decarboxylase polypeptide that we purified has an apparent molecular weight of 24 kDa and is encoded in the carboxyl-terminal region of the ORF. A portion of the cDNA encoding this region was expressed in E. coli, and a polyclonal antibody was developed against the expressed polypeptide. The antibody detects 34 kDa and 24 kDa polypeptides on Western blots of oat leaf samples. Maturation of arginine decarboxylase in oats appears to include processing of a precursor protein. PMID- 2266947 TI - Structure and tissue-specific regulation of genes encoding barley (1----3, 1--- 4)-beta-glucan endohydrolases. AB - Two genes encode (1----3, 1----4)-beta-glucan 4-glucanohydrolase (EC 3.2.1.73) isoenzymes in barley. A gene for isoenzyme EI has been isolated from a barley genomic library and the nucleotide sequence of a 4643 bp fragment determined. The gene is located on barley chromosome 5 while the gene for (1----3, 1----4)-beta glucanase isoenzyme EII is carried on chromosome 1. The isoenzyme EI gene contains a single 2514 bp intron that is inserted in codon 25 of a sequence encoding a signal peptide of 28 amino acids. The coding region of the mature enzyme is characterized by a high G+C content, which results from an extreme bias towards the use of these nucleotides in the wobble base position of codons. Determination of the nucleotide sequence of the gene has enabled the complete primary structure of the enzyme to be deduced: isoenzyme EI shows 92% positional identity with the primary sequence of (1----3, 1----4)-beta-glucanase isoenzyme EII at both the nucleotide and amino acid level. However, the nucleotide sequences of the two genes diverge markedly in their 3' untranslated regions. Expression sites of the two genes were defined by Northern analysis using oligonucleotide probes specific for these 3' untranslated regions and by amplifying specific cDNAs through the polymerase chain reaction. In the tissues examined, transcription of the isoenzyme EII gene is restricted to the aleurone layer of germinated grain. In contrast, the gene for isoenzyme EI is transcribed at relatively high levels in young leaves, but also in the scutellum and aleurone of germinated grain. PMID- 2266948 TI - Analysis of expression and evolutionary relationships of phosphoenolpyruvate carboxylase genes in Flaveria trinervia (C4) and F. pringlei (C3). AB - Phosphoenolpyruvate carboxylase (PEPCase) was shown to be encoded by a multigene family in various Flaveria species analysed. Several clones were isolated from genomic libraries of F. pringlei (C3 species) and F. trinervia (C4 species) and classified into four distinct groups according to their hybridization behaviour to a full-length cDNA clone encoding the PEPCase C4 isozyme of F. trinervia. A detailed cross-hybridization analysis demonstrated that the closest relative of most of the PEPCase genes isolated from F. trinervia and F. pringlei was not found in the same but in the other species. Northern analysis, using stringent conditions, allowed discrimination of class-specific PEPCase transcripts and revealed characteristic organ-specific expression patterns. PMID- 2266949 TI - Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants. AB - Tomato plants were transformed with a chimaeric polygalacturonase (PG) gene, designed to produce a truncated PG transcript constitutively. In these plants expression of the endogenous PG gene was inhibited during ripening, resulting in a substantial reduction in PG mRNA and enzyme accumulation. This inhibition was comparable to that achieved previously using antisense genes. The expression of the truncated gene in ripe fruit was substantially lower than its expression in green fruit. Thus expression of both the endogenous and truncated genes is reduced in ripe fruit in which both are active. The implication of this observation is discussed in relation to the possible mechanism whereby sense constructs inhibit gene expression. PMID- 2266950 TI - Cloning and characterization of the Azotobacter vinelandii recA gene and construction of a recA deletion mutant. AB - The recA gene of Azotobacter vinelandii was isolated from a genomic library by heterologous complementation of an Escherichia coli recA mutation for resistance to UV radiation. The A. vinelandii recA gene was localized on adjacent PstI fragments of 1.3 and 1.7 kb. The cloned A. vinelandii recA gene was functionally analogous to the E. coli recA gene. It was also able to complement the E. coli recA mutation for homologous recombination. A recA deletion mutant of A. vinelandii was constructed. This mutant was sensitive to DNA-damaging agents like UV rays, methyl methane sulfonate (MMS) and nalidixic acid and was deficient in homologous recombination. PMID- 2266951 TI - 13C NMR studies of fatty acid-protein interactions: comparison of homologous fatty acid-binding proteins produced in the intestinal epithelium. AB - A high-resolution, solution-state NMR method for characterizing and comparing the interactions between carboxyl 13C-enriched fatty acids (FA) and individual binding sites on proteins has been developed. The utility of this method results from the high degree of resolution of carboxyl from other carbon resonances and the high sensitivity of FA carboxyl chemical shifts to intermolecular environmental factors such as degree of hydrogen-bonding or hydration, degree of ionization (pH), and proximity to positively-charged or aromatic side-chain moieties in proteins. Information can be obtained regarding binding heterogeneity (structural as well as thermodynamic), binding stoichiometries, relative binding affinities, the ionization behavior of bound FA and protein side-chain moieties, the physical and ionization states of unbound FA, and the exchange rates of FA between protein binding sites and between protein and non-protein acceptors of FA, such as model membranes. Cytosolic fatty acid binding proteins represent an excellent model system for studying and comparing fatty acid-protein interactions. Prokaryotic expression vectors have been used to direct efficient synthesis of several mammalian intestinal FABPs in E. coli. This has enabled us to isolate gram-quantities of purified FABPs, to introduce NMR-observable isotopes, and to generate FABP mutants. The intestine is the only tissue known to contain abundant quantities of more than one FABP homologue in a single cell type. It is likely that these homologous FABPs serve distinct functional roles in intestinal lipid transport. This paper presents comparative 13C NMR results for FA interactions with FABP homologues from intestine, and the functional implications of these analyses are discussed. PMID- 2266952 TI - Detection, tissue distribution and (sub)cellular localization of fatty acid binding protein types. AB - This overview of recent work on FABP types is focussed on their detection and expression in various tissues, their cellular and subcellular distribution and their binding properties. Besides the 3 well-known liver, heart and intestinal types, new types as the adipose tissue, myelin and (rat) renal FABPs have been described. Recent observations suggest the occurrence of more tissue-specific types, e.g. in placenta and adrenals. Heart FABP is widely distributed and present in skeletal muscles, kidney, lung, brain and endothelial cells. The cellular distribution of FABP types appears to be related to the function of the cells in liver, muscle and kidney. The presence of FABP in cellular organelles requires more evidence. The functional significance of the occurrence of more FABP types is unclear, in spite of the observed differences in their ligand protein interaction. PMID- 2266953 TI - Fatty acid-binding protein from human heart localized in native and denaturing two-dimensional gels. AB - A group of low molecular weight fatty acid-binding cytosolic proteins, FABPc, with high abundance in heart, liver, skeletal muscle, intestine and adipose tissue, are anticipated to play a role in long-chain fatty acid metabolism in these tissues. Recently, a FABPc with Mr 15 kDa has been purified from human heart muscle and found to be present in levels 2-4% of cytosolic proteins of human heart myocytes. In the present study two-dimensional gel electrophoresis under native and denaturing conditions has been used to characterize FABPc from human heart and this protein is found to be a major protein of human heart myocytes. The pI of FABPc from human heart was found to be about 5.3 under native conditions and about 6.5 in the presence of 9 M urea. PMID- 2266954 TI - Revision of the amino acid sequence of human heart fatty acid-binding protein. AB - Cardiac-type fatty acid-binding protein (cFABP) from human heart muscle of three individuals was isolated and characterized as pI 5.3-cFABP. The proteins were structurally analyzed by tryptic peptide mapping, application of plasma desorption time-of-flight mass spectrometry and amino acid sequencing. All three preparations of human heart FABP, having 132 amino acids, differed from the published sequence [Offner et al. Biochem J 251: 191-198, 1988] in position 104, where Leu is found instead of Lys, and in position 124, where Cys is found instead of Ser. PMID- 2266955 TI - The chemical modification of cysteine-69 of rat liver fatty acid-binding protein (FABP): a fluorescence approach to FABP structure and function. AB - Hepatic-FABP was labelled at cysteine-69 with the fluorescent environmentally sensitive reporter group AEDANS. The labelled protein had an emission maximum at 465 nm indicating that cysteine-69 was buried in a non-polar environment. The modified protein was still able to bind ligands such as oleic acid, oleoyl CoA and haem. The affinity of AEDANS-FABP for haem was unaltered as compared with the native protein indicating that cysteine-69 must be remote from the ligand binding site. The binding of oleic acid did not significantly perturb the fluorescence emission spectrum of the fluorescent reporter group suggesting that there are not large conformational changes in the region of cysteine-69 on fatty acid binding. The binding of stoichiometric amounts of oleoyl CoA was accompanied by a small fluorescence enhancement which suggests that fatty acyl CoAs may interact with other regions of the FABP molecule not involved in fatty acid binding. PMID- 2266956 TI - A comparison of heart and liver fatty acid-binding proteins: interactions with fatty acids and possible functional differences studied with fluorescent fatty acid analogues. AB - Fatty acid-binding proteins (FABP) are distinct but related gene products which are found in many mammalian cell types. They are generally present in high abundance, and are found in those tissues where free fatty acid (ffa) flux is high. The function(s) of FABP is unknown. Also not known is whether all FABP function similarly in their respective cell types, or whether different FABP have unique functions. The purpose of these studies was to assess whether different members of the FABP family exhibit different structural and functional properties. Two fluorescent analogues of ffa were used to compare the liver (L FABP) and heart (H-FABP) binding proteins. The propionic acid derivative of diphenylhexatriene (PADPH) was used to examine the physical properties of the ffa binding site on L- and H-FABP, as well as the relative distribution of ffa between FABP and membranes. An anthroyloxy-derivative of palmitic acid, 2AP, was used to monitor the transfer kinetics of ffa from liver or heart FABP to acceptor membranes, using a resonance energy transfer assay. The results demonstrate that the ffa binding sites of both FABP are hydrophobic in nature, although the L-FABP site is more nonpolar than the H-FABP site. Equilibration of PADPH between L-FABP and phosphatidylcholine (PC) bilayers resulted in a molar partition preference of greater than 20: 1, L-FABP PC. Similar studies with H-FABP resulted in a PADPH partition preference of only 3:1, H-FABP: PC. Finally, the transfer of 2AP from H FABP to acceptor membranes was found to be 50-fold faster than transfer from L FABP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2266957 TI - Role of fatty acid-binding protein in cardiac fatty acid oxidation. AB - Although abundant in most biological tissues and chemically well characterized, the fatty acid-binding protein (FABP) was until recently in search of a function. Because of its strong affinity for long chain fatty acids and its cytoplasmic origin, this protein was repeatedly claimed in the literature to be the transcytoplasmic fatty acid carrier. However, techniques to visualize and quantify the movements of molecules in the cytoplasm are still in their infancy. Consequently the carrier function of FABP remains somewhat speculative. However, FABP binds not only fatty acids but also their CoA and carnitine derivatives, two typical molecules of mitochondrial origin. Moreover, it has been demonstrated and confirmed that FABP is not exclusively cytoplasmic, but also mitochondrial. A function for FABP in the mitochondrial metabolism of fatty acids plus CoA and carnitine derivatives would therefore be anticipated. Using spin-labelling techniques, we present here evidence that FABP is a powerful regulator of acylcarnitine flux entering the mitochondrial beta-oxidative system. In this perspective FABP appears to be an active link between the cytoplasm and the mitochondria, regulating the energy made available to the cell. This active participation of FABP is shown to be the consequence of its gradient-like distribution in the cardiac cell, and also of the coexistence of multispecies of this protein produced by self-aggregation. PMID- 2266958 TI - Fatty acid-binding protein expression in the liver: its regulation and relationship to the zonation of fatty acid metabolism. AB - Liver fatty acid-binding protein (L-FABP) is expressed in a declining gradient between the portal and central zones of the liver acinus. This paper discusses the results of experimental studies which address the questions: (a) What factors regulate L-FABP expression in liver and produce its acinar gradient? (b) What is the relationship between the acinar gradient of L-FABP and acinar gradients in the transport and metabolism of long-chain fatty acids? Both high-fat diets and clofibrate-treatment increase L-FABP proportionally at both extremes of the liver acinus and the small intestine, with preservation of the L-FABP gradient in both tissues. Female rats differ from males, however, in showing a greater hepatic abundance of L-FABP which is expressed almost equally throughout the acinus. Dietary studies show that L-FABP is induced with increased fatty acid flux derived from dietary fat but not from de novo hepatic fatty acid synthesis. Studies of the synthesis and utilization of fatty acids by hepatocytes isolated from the periportal and pericentral zones of the liver acinus suggest that the acinar gradient of L-FABP is not associated with differences in the intrinsic capacity of zone 1 and zone 3 hepatocytes to utilize or synthesize fatty acids. In addition, studies of the acinar uptake pattern of a fluorescent fatty acid derivative by isolated perfused livers indicate that the acinar distribution of L FABP does not determine the pattern of fatty acid uptake in the intact acinus. Rather, the acinar gradient of L-FABP is most likely to represent a response to physiological conditions existing in the intact acinus which may include gradients in the flux of fatty acids, fatty acid metabolites and hormones. PMID- 2266959 TI - Quantitation of plasma membrane fatty acid-binding protein by enzyme dilution and monoclonal antibody based immunoassay. AB - A plasma membrane fatty acid-binding protein (h-FABPpm) has been isolated from rat hepatocytes. Analogous proteins have also been identified in adipocytes, jejunal enterocytes and cardiac myocytes, all cells with high transmembrane fluxes of fatty acids. These 43 kDa, highly basic (pI = 9.1) FABPpm's appear unrelated to the smaller, cytosolic FABP's (designated FABP's) identified previously in the same tissues. h-FABPpm appears closely related to the mitochondrial isoform of glutamic-oxaloacetic transaminase (mGOT), and both the purified protein and liver cell plasma membranes (LPM) possess GOT enzymatic activity. From their relative GOT specific activities it is estimated that h FABPpm constitutes approximately 2% of LPM protein, or about 0.7 x 10(7) sites per cell. A monoclonal antibody-based competitive inhibition enzyme immunoassay (CIEIA) for h-FABPpm is described; it yields an estimate of 3.4 x 10(7) h-FABPpm sites per hepatocyte. Quantitated by either method, h-FABPpm appears to be a highly abundant protein constituent of LPM. PMID- 2266960 TI - The membrane fatty acid-binding protein is not identical to mitochondrial glutamic oxaloacetic transaminase (mGOT). AB - For evaluation whether the membrane fatty acid-binding protein is related to mGOT, studies on the structure and function of both purified proteins were performed. Physicochemical characterization revealed that both proteins are different: the membrane fatty acid-binding protein has a molecular weight of 40 kD and a pI of 8.5-9.0, whereas rat mGOT has a molecular weight of 44 kD and a pI of 9.5-10.0. According to this distinct differences, they migrated separately on 2-dimensional electrophoresis. Furthermore, monospecific antibodies against the membrane fatty acid binding protein did not react with rat mGOT. In co chromatography studies only the membrane fatty acid-binding protein showed affinity for long chain fatty acids, but not mGOT. Moreover, membrane binding studies were performed with the monospecific antibody to the membrane fatty acid binding protein. The inhibitory effect of this antibody on plasma membrane binding of oleate was reversed after preabsorption of the antibody with the membrane fatty acid binding protein, but was not affected after preabsorption with mGOT. These results indicate that the membrane fatty acid binding protein and mGOT are structurally and functionally not related. The data also support the significance of this membrane protein in the plasma membrane binding process of long chain fatty acids. PMID- 2266961 TI - Fatty acid-binding to erythrocyte ghost membranes and transmembrane movement. AB - Palmitate binding to human erythrocyte ghost membranes has been investigated with ghost preparations suspended in 0.2% albumin solutions. Free unbound palmitate in the extracellular water phase was measured in equilibrium studies using albumin filled acid loaded ghosts as small semipermeable bags. The apparent dissociation constant of binding to the membrane is 13.5 nM and the binding capacity 19 nmoles per 7.2 x 10(9) cells. The 0 degree C exchange efflux kinetics of palmitate from albumin-filled ghosts is described by a model, which provides estimates of the rate constant of membrane transfer, k3 = 0.024 s-1, independent of the molar ratio of palmitate to albumin (v) and of a mean dissociation rate constant of the palmitate-albumin complex, k1 = 0.0015 s-1 at v 0.2, allowing for a heterogeneity of the palmitate binding to albumin. The values of a third kinetically determined v dependent model constant, Q, the ratio of palmitate bound to the membrane inner surface to palmitate on intracellular albumin, are not different from the Q values obtained by equilibrium experiments. The temperature dependences of k1 and k3 in the interval 0 degrees C to 15 degrees C give activation energies of 96 and 103 kJ/mole, respectively. The 0 degrees C exchange efflux increases about 2 fold in response to a rise of pH from 6 to 9. The results suggest a carrier mediated palmitate flux at low v with a Vmax about 2 pmoles min-1 cm-2 at 0 degrees C pH 7.3. PMID- 2266962 TI - Acyl-CoA-binding protein (ACBP) and its relation to fatty acid-binding protein (FABP): an overview. AB - Acyl-CoA-binding protein is a 10 Kd protein which binds medium- and long-chain acyl-CoA esters with high affinity. The concentration in liver is 2-4 times the acyl-CoA concentration. ACBP has much greater affinity for acyl-CoA than FABP. FABP from bovine heart and liver is unable to compete with multilamellar liposomes, Lipidex and microsomal membrane in binding acyl-CoA esters, whereas ACBP effectively extracts acyl-CoA from all those sources. Previously published results on the effect of FABP on acyl-CoA metabolism need to be reevaluated due to possible contamination with ACBP. Recently it was discovered that ACBP is identical to a putative neurotransmitter diazepam binding inhibitor. The possibility therefore exists that ACBP has more than one function. PMID- 2266963 TI - Liver fatty acid-binding protein in two cases of human lipid storage. AB - FABPs in the various tissues play an important role in the intracellular fatty acid transport and metabolism. Reye's syndrome (RS) and multisystemic lipid storage (MLS) are human disorders characterized by a disturbance of lipid metabolism of unknown etiology. We investigated for the first time L-FABP in these two conditions. Affinity purified antibodies against chicken L-FABP were raised in rabbits, and found to cross-react specifically with partially purified human L-FABP. L-FABP content in liver samples of two patients with RS and MLS was investigated by immuno-histochemistry, SDS-PAGE and ELISA. L-FABP immuno histochemistry showed increased reactivity in the liver of RS patient and normal reactivity in MLS liver. L-FABP increase in RS liver was confirmed by densitometry of SDS-PAGE and ELISA method. By these two methods the increase amounted to 180% and 199% (p less than 0.02), respectively, as compared to controls. A possible role of L-FABP in the pathogenesis of RS is discussed. PMID- 2266964 TI - Nomenclature of fatty acid-binding proteins. AB - A variety of designations is currently being used to refer to cellular fatty acid binding proteins (FABPs). Besides from the use of other general names (e.g. Z protein), confusion mostly arises from the application of various abbreviations and symbols to denote the tissue(s) of origin and cellular localization (cytoplasm, plasma membrane) of a specific FABP. In order to minimize confusion a more unified and rational nomenclature is proposed, which is based on application of the formula X-FABPY. The prefix X is a capital letter indicating the tissue of greatest abundance, the suffix Y similarly denotes the (sub)cellular localization of the protein. The general and functional name 'fatty acid-binding protein' (FABP) is preferred for the cellular proteins with the property to bind fatty acids, unless future research reveals that the binding of fatty acids is not the primary biological property or physiological role of (some of) these proteins. PMID- 2266966 TI - Localization of liver fatty acid-binding protein and its mRNA in the liver and jejunum of rats: an immunohistochemical and in situ hybridization study. AB - The localization of liver fatty acid-binding protein (L-FABP) and its mRNA in the liver and jejunum was examined in normal and 3-day-fasted rats by means of immunohistochemistry using a specific antibody to L-FABP and in situ hybridization using a synthetic oligonucleotide complementary to L-FABP mRNA as probe. In the liver from normally fed rats, the signal for L-FABP mRNA in hepatocytes was distributed throughout the lobule, with higher intensity in the periportal than in the centrolobular region. After a 3-d fasting, the mRNA signal declined in intensity throughout the lobule, in accordance with the result of Northern blot analysis. Immunohistochemistry for L-FABP showed intralobular patterns of immunoreactivity similar to those of the mRNA signal in both fed and fasted animals. In the jejunum from fed rats, L-FABP-mRNA signal was abundant in the absorptive epithelial cells lining the lower two-thirds of villus and less abundant in the villus tip cells, while the intensity of L-FABP immunoreactivity remained high in the latter cells. Fasting brought about a downward shift of the mRNA signal to an area including the upper half of the crypt and the lower portions of villus, with decreased intensity in the rest of the villus. Immunohistochemistry also showed a downward extension of the immunoreactivity into the upper crypt area. The present results suggest that in situ hybridization is a useful tool to analyze regulations of the expression of L-FABP gene in the digestive organs in association with epithelial cell migration and dietary condition. PMID- 2266967 TI - Historic overview of studies on fatty acid-binding proteins. AB - Fatty acid-binding proteins (FABPs) were first identified in the cytosol of rat intestinal mucosa during studies on the regulation of intestinal fatty acid uptake. The subsequent finding of FABP activity in the cytosol of many other tissues initially was believed to reflect a single protein. However, the FABPs are now recognized as products of an ancient gene family comprised of at least 9 structurally related, solube intracellular members, a number of which exhibit high-affinity binding of long-chain fatty acids. Despite recent insights into regulation and tissue-specific expression suggesting FABPs to subserve diverse roles, their precise biological functions remain to be elucidated. PMID- 2266968 TI - Amino acid sequence and some ligand binding properties of fatty acid-binding protein from bovine brain. AB - A fatty acid-binding protein (FABP) from the cytosol of bovine brain was purified by Sephadex G-75 filtration and electrofocusing. The purified protein migrated as a single protein band in 15% polyacrylamide gel electrophoresis with an apparent molecular mass of 14.7 kDa. To ascertain that the purified protein was a FABP, it was submitted to fatty acid-binding tests. Oleic and palmitic acids bound to brain FABP but this was not the case for palmitoyl CoA. By Scatchard analysis the ligand binding values were: Kd = 0.28 microM, Bmax (mol/mol) = 0.6 for oleic acid and Kd = 0.8 microM, Bmax (mol/mol) = 2.1 for palmitic acid. The complete amino acid sequence of the brain FABP was determined and a microheterogeneity was observed. Sequence comparison with other FABPs of known sequence and the observed microheterogeneity demonstrated the presence in brain of several homologous FABPs closely related to heart FABP. PMID- 2266965 TI - Cellular fatty acid-binding proteins: current concepts and future directions. AB - At least three different proteins are implicated in the cellular transport of fatty acid moieties: a plasmalemmal membrane and a cytoplasmic fatty acid-binding protein (FABPPM and FABPC, respectively) and cytoplasmic acyl-CoA binding protein (ACBP). Their putative main physiological significance is the assurance that long chain fatty acids and derivatives, either in transit through membranes or present in intracellular compartments, are largely complexed to proteins. FABPC distinguishes from the other proteins in that distinct types of FABPC are found in remarkable abundance in the cytoplasmic compartment of a variety of tissues. Although their mechanism of action is not yet fully elucidated, current knowledge suggests that the function of this set of proteins reaches beyond simply aiding cytoplasmic solubilization of hydrophobic ligands, but that they can be assigned several regulatory roles in cellular lipid homeostasis. PMID- 2266969 TI - Bifunctional lipid-transfer: fatty acid-binding proteins in plants. AB - A cytosolic protein, able to facilitate intermembrane movements of phospholipids in vitro, has been purified to homogeneity from sunflower seedlings. This protein, which has the properties of a lipid-transfer protein (LTP), is also able to bind oleoyl-CoA, as shown by FPLC chromatography. This finding, in addition to previous observations suggesting that a lipid-transfer protein from spinach leaves can bind oleic acid and that oat seedlings contain a fatty acid-binding protein with similar features than lipid transfer proteins, provides a clear demonstration that plant cells contain bifunctional fatty acid/lipid transfer proteins. These proteins can play an active role in fatty acid metabolism which involves movements of oleyl-CoA between intracellular membranes. PMID- 2266970 TI - Characteristics of fatty acid-binding proteins and their relation to mammary derived growth inhibitor. AB - Based on sequence relationships the cytoplasmic fatty acid-binding proteins (FABPs) of mammalian origin are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. Highly conserved sequences of FABPs within the same type correlate with immunological crossreactivities. Isoforms of hepatic-type FABP are found in several mammalian species and for bovine liver FABP specific shifts in isoelectric points upon lipidation with fatty acids are observed. Isoforms of intestinal-type FABP are not known and the occurrence of cardiac-type isoforms so far is confined to bovine heart tissue. A bovine mammary-derived growth inhibitor (MDGI) is 95% homologous to the cardiac type FABP from bovine heart. Dissociation constants of FABP/fatty acid complexes are in the range of 1 microM and 1:1 stoichiometries are usually found, but the neutral isoform of hepatic FABP from bovine liver binds 2 fatty acids. On subcellular levels hepatic- and cardiac-type FABPs are differently distributed. Though mainly cytosolic in either case, immunoelectron microscopy as well as a gelchromatographic immunofluorescence assay demonstrate the association of hepatic FABP in liver cells with microsomal and outer mitochondrial membranes and with nuclei, whereas in heart cells cardiac FABP is confined to mitochondrial matrix and nuclei. In mammary epithelial cells MDGI is associated with neither mitochondria nor endoplasmic reticulum, and is expressed in a strictly developmental-dependent spatial and temporal pattern. The specific role proposed for MDGI is to arrest growth of mammary epithelial cells when they become committed to differentiation in the mammary gland. PMID- 2266971 TI - Expression of a functionally active cardiac fatty acid-binding protein in the yeast, Saccharomyces cerevisiae. AB - The unicellular eukaryotic microorganism, Saccharomyces cerevisiae, transformed with a plasmid containing a cDNA fragment encoding bovine heart fatty acid binding protein (H-FABP) under the control of the inducible yeast GAL10 promoter, expressed FABP during growth on galactose. The maximum level of immunoreactive FABP, identical in size to native protein as judged from SDS-polyacrylamide gel electrophoresis, was reached after approximately 16 hours of induction. Analysis of particulate and soluble subcellular fractions showed that FABP was exclusively associated with the cytosol. FABP expressed in yeast cells was functional as was demonstrated by its capacity to bind 14C-oleic acid in an in vitro assay. Growth of the transformants on galactose as the carbon source was significantly retarded at 37 degrees C. Whereas the fatty acid pattern of total lipids was not altered in transformed cells, desaturation of exogenously added 14C-palmitic acid was significantly reduced both at 30 and 37 degrees C. The lowest percentage of radioactively labeled unsaturated fatty acids was found in the phospholipid fraction. PMID- 2266972 TI - Expression of fatty acid-binding protein from bovine heart in Escherichia coli. AB - The coding part of the cDNA of cardiac fatty acid-binding protein (cFABP) from bovine heart was cloned into the vector pKK233-2. After induction with isopropyl beta-D-thiogalactopyranoside cFABP was found in a soluble form in the cytosol of plasmid transformed E. coli amounting up to 5.7% of the soluble protein. cFABP was detected after SDS-polyacrylamide gelelectrophoresis and/or isoelectric focusing and Western blot by immuno-staining and was determined quantitatively by a solid phase enzyme-linked immuno sorbent assay. The cFABP produced by bacteria binds oleic acid with high affinity as shown by comigration of protein and ligand in both gelfiltration and isoelectric focusing. cFABP was purified from bacterial lysates to near homogeneity and resolved into four isoproteins. PMID- 2266973 TI - Expression of rat intestinal fatty acid binding protein in E. coli and its subsequent structural analysis: a model system for studying the molecular details of fatty acid-protein interaction. AB - A prokaryotic expression vector containing the rec A promoter and a translational enhancer element from the gene 10 leader of bacteriophage T7 was used to direct efficient synthesis of rat intestinal fatty acid binding protein (I-FABP) in E. coli. Expression of I-FABP in E. coli has no apparent, deleterious effects on the organism. High levels of expression of I-FABP mRNA in supE+ strains of E. coli, such as JM101, is associated with suppression of termination at its UGA stop codon. This can be eliminated by using a supE-strain as MG1655 and by site directed mutagenesis of the cDNA to create an in frame UAA stop codon. E. coli derived rat I-FABP lacks its initiator Met residues. It has been crystallized with and without bound palmitate. High resolution x-ray crystallographic studies of the 131 residue apo- and holo-proteins have revealed the following. I-FABP contains 10 anti-parallel beta-strands organized into two orthogonally situated beta-sheets. The overall conformation of the protein resembles that of a clam- hence the term beta-clam. The bound ligand is located in the interior of the protein. Its carboxylate group forms part of a unique five member hydrogen bonding network consisting of two ordered solvent molecules as well as the side chains of Arg106 and Gln115. The hydrocarbon chain of the bound C16:0 fatty acid has a distinctive bent conformation with a slight left-handed helical twist. This conformation is maintained by interactions with the side chains of a number of hydrophobic and aromatic amino acids. Apo-I-FABP has a similar overall conformation to holo-I-FABP indicating that the beta-clam structure is stable even without bound ligand. The space occupied by bound ligand in the core of the holo-protein is occupied by additional ordered solvent molecules in the apo protein. Differences in the side chain orientations of several residues located over a potential opening to the cores of the apo- and holo-proteins suggest that solvent may play an important role in the binding mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2266975 TI - The micronucleus assay in Anodonta cygnea for the detection of drinking water mutagenicity. AB - A micronucleus test in gill cells of the freshwater mussel Anodonta cygnea has been proposed for the detection of drinking water genotoxicity. Animals were exposed for 28 days to a drinking water sample and collected every week. Highly significant increases in spontaneous MN frequency were observed at each sampling, especially after 13 days of exposure. As positive control 2 doses of mytomicin C (MMC) were used (10(-8) and 10(-7) M). A second experiment was performed at a municipal waterworks in order to assess the role of water treatment processes in the production of mutagenic compounds. The most prevalent genotoxic effects were detected after chlorination (mean: 10.47% +/- 3.05, p less than 0.001). PMID- 2266976 TI - Methapyrilene: DNA as a possible target. AB - The structural features contributing to the potential carcinogenicity, DNA reactivity and genotoxicity of methapyrilene and its non-carcinogenic congener pyrilamine were examined. The analyses suggest that the former has the potential for DNA-reactivity, a property which is absent from the latter. PMID- 2266974 TI - Crystal structure of chicken liver basic fatty acid-binding protein at 2.7 A resolution. AB - The three-dimensional structure of chicken liver basic fatty acid-binding protein has been determined at 2.7 A resolution by X-ray crystallography. Phases were calculated using the multiple isomorphous replacement procedure and a preliminary model was built. This model, with an initial R-factor of 0.57, was then improved by a cycle of refinement by simulated annealing which brought the R factor down to 0.32. The protein is structured as a compact 10-stranded-beta-barrel which encapsulates a residual electron density that can be interpreted as a fatty acid molecule. The NH2-terminus portion of the molecule contains two short alpha helices. The structure of this liver protein appears very similar to that of the Escherichia coli derived rat intestinal FABP recently determined by X-ray diffraction methods. PMID- 2266977 TI - N-2 acetylation of 2'-deoxyguanosine by coffee mutagens, methylglyoxal and hydrogen peroxide. AB - Coffee shows direct-acting mutagenicity in Salmonella typhimurium TA100 and most of this mutagenicity is due to the synergistic effects of methylglyoxal and hydrogen peroxide. The modifications of deoxyribonucleosides by methylglyoxal plus hydrogen peroxide were studied in vitro. When 2'-deoxyguanosine (6.25 mumole) was treated with methylglyoxal (125 mumole) and hydrogen peroxide (125 mumole) in 5 ml of 0.1 M phosphate buffer (pH 7.4) at 37 degrees C for 3 h, N2 acetyl-2'-deoxyguanosine was formed with a yield of 1.1%. Its formation increased time-dependently. By contrast, no appreciable modification of other deoxynucleosides was detected after their incubation with methylglyoxal and hydrogen peroxide under similar conditions. N2-Acetyl-2'-deoxyguanosine was also formed during incubation of 2'-deoxyguanosine with instant coffee. PMID- 2266978 TI - The effect of multi-locus deletions in heterozygotes; a model study using Drosophila. AB - In a model study using Drosophila, we examined the heterozygous effects of a number of well-defined X-chromosomal deletions (i.e., those differing in location, but of about the same length, and those differing in length but located in the same general region), using relative viability and/or fertility as indicators. Most of the deletions were originally isolated in radiation or chemical mutagenesis experiments and maintained since then in stocks using appropriate balancer chromosomes. The results show that (i) most of the deletions have pronounced deleterious effects in heterozygotes; (ii) the size of the deletion per se is not a critical factor in determining relative heterozygous viability, but its location is and (iii) it is possible to tentatively identify, with respect to the deletions, putative genes that affect viability in Drosophila. PMID- 2266979 TI - Mutagenicity of mononitrodihydrobenzo[a]pyrenes. PMID- 2266980 TI - Influence of DNA repair deficiencies on the UV sensitivity of yeast cells in different cell cycle stages. AB - Synchronously dividing haploid yeast cells were UV-irradiated in various stages of the cell cycle after release from alpha-factor arrest. In confirmation of earlier results (Chanet et al., 1973), in wild-type strains G1/S phase cells were found to be the most sensitive and late S/G2 cells the most resistant. Stationary phase (G0) cells were significantly more UV resistant than G1 cells. Strains defective in nucleotide excision repair lost enhanced resistance in the G2 phase and were most UV-sensitive in the G0 state. Reduced G2 resistance was also observed in rad6 mutants but not in rad9 mutants. After UV-irradiation in G1 phase rad9 mutant cells showed a reduced G1/S phase arrest. PMID- 2266981 TI - Comparison of sister-chromatid exchange frequencies in mouse T- and B-lymphocytes after exposure to 4-hydroxycyclophosphamide or phosphoramide mustard. AB - The present study was designed to investigate the genotoxicity of 4 hydroxycyclophosphamide (4-OHCP) and phosphoramide mustard (PAM), both reactive metabolites of cyclophosphamide (CP), for possible differences in SCE-inducing activity in mouse T- and B-lymphocytes. Mouse peripheral blood lymphocytes were isolated and stimulated to divide with either phytohemagglutinin (T-cell mitogen) or lipopolysaccharide (a polyclonal B-cell activator). Significant concentration dependent increases in SCE frequencies were observed for both 4-OHCP and PAM with both mitogens, with 4-OHCP being almost twice as potent as PAM. There was no difference in SCE response between T- and B-lymphocytes after exposure to either PAM or 4-OHCP. These data do not support the idea that the difference in SCE response in T- and B-lymphocytes by CP in vivo is due to differential responses to either of the proposed putative metabolites of CP. PMID- 2266982 TI - Chromosome aberrations in rotogravure printing plant workers. AB - Chromosome analysis was carried out in peripheral lymphocytes of 3 groups of workers. In 42 rotogravure printers exposed to rotogravure printing dyes and highly purified toluene at working air concentrations in the range of 104-1170 ppm (390-4380 mg/m3) for 13 years on average, an increased incidence of aberrant cells and chromatid breaks was observed. In 28 office and technical employees of the same plant, more than half of whom worked 2 h daily in the rotogravure workshop, an increased percentage of aberrant cells and chromatid breaks was also found. The difference between the 2 groups working in the printing plant and 32 controls was highly significant. The high incidence of aberrations could be explained by the exposure to toluene, but the influence of rotogravure printing dyes cannot be excluded. Smoking and high air pollution in the urban area were contributing factors in all 3 groups. PMID- 2266983 TI - Induction of chromosome damage by aniline and its C-hydroxylated metabolites in the root cells of Vicia faba. AB - The induction of sister-chromatid exchanges (SCEs) and chromosome aberrations (CAs) by aniline hydrochloride (AH) and its C-hydroxylated metabolites, o-, m- and p-aminophenol, in the root cells of Vicia faba was examined. AH induced CAs, but not SCEs. All the C-hydroxylated metabolites of aniline induced both SCEs and CAs. However, the treatment of cells with these metabolites at concentrations that did not cause significant increases in CAs resulted in significant increases in SCEs. These results seem to suggest that the substance that induced CAs in root cells treated with AH was not the C-hydroxylated metabolites of aniline. PMID- 2266984 TI - Latencies of peripheral nerve and cerebral evoked responses to air-puff and electrical stimuli. AB - This study examined the latency relationship between mechanically and electrically elicited sensory nerve action potentials (SNAPs) and the somatosensory-evoked potentials (SEPs) they produce. Brief air-puff and electrical stimuli were applied to the tip of the index finger in separate trials and SNAPs from the median nerve at the wrist and SEPs from the scalp were recorded for each stimulus presentation. Air-puff evoked SNAPs were polyphasic, usually consisting of 2 to 4 separate waves, unlike triphasic activity elicited by electrical stimulation. The SEPs produced by these 2 distinct forms of inputs, however, were similar in morphology. The latencies of the initial components of SNAPs and SEPs were longer for air-puff stimulation. The conduction time, however, of the fastest afferent volleys from the wrist to cortex was not significantly different for air-puff (20.52 +/- 1.06 ms, mean +/- SD) and electrical stimulation (20.17 +/- 0.66 ms). It is therefore concluded that the latency delays for air-puff evoked SNAPs and SEPs are due solely to a transduction time at the skin receptors and not due to differences in conduction velocities as suggested in the previous literature. PMID- 2266985 TI - Twitch relaxation of the cat soleus muscle at different lengths and temperatures. AB - We recorded isometric and isotonic twitches, in situ, from the cat soleus at various muscle lengths and temperatures. At a given temperature the duration of isometric twitches increased approximately 60% for each 10% increase in muscle length, which was primarily owing to decreases in the rate of relaxation. For the relaxation of isometric twitches recorded at different muscle lengths, the equivalent activation energies determined were the same (13.2 +/- 0.3 kcal/M). The duration of isotonic twitch contractions increased only 20% for each 10% increase in muscle length. Even a small amount of shortening (3%) diminished the dependence of twitch duration on muscle length. In this case, twitch duration increased approximately 30% for every 10% increase in muscle length. Hence, even small changes in internal and/or external compliance (eg, changes in the tendon fiber continuity) can greatly influence twitch duration. Our findings are consistent with the hypotheses that in the cat soleus, Ca2+ sequestration is primarily governed by a single energy dependent process and that the Ca2+ sensitivity of the contractile apparatus increases with increasing sarcomere length. PMID- 2266986 TI - Central motor conduction: method and normal results. AB - Normal results of CMCT to upper extremities do not correlate with height, age, or sex. In cases of peripheral conduction slowing, upper limits of CMCT must be adapted. Cervical root excitation can be carried out by electrical or magnetic stimulation. The F wave technique also produces reliable results. Electrical stimulation of lumbar roots produces the most reliable results when measuring CMCT to leg muscles. CMCT to the tibialis anterior correlates with height, but not with age or sex. The same is true for intraspinal motor conduction time. Contraction of the target muscle enlarges CMAP amplitudes after cervical and transcranial stimulation. However, a latency shortening is only seen after brain stimulation. This is thought to be at least partially due to spatial summation of D and I waves. Age affects peripheral nerve conduction and central nerve conduction in different ways. PMID- 2266987 TI - Motor unit spike counts before and after maximal voluntary contraction. AB - Motor unit spike counts in the biceps brachii muscle were evaluated using a monopolar needle electrode during maintenance of antigravity posture with the elbow flexed to 45 degrees before and after maximal voluntary contraction (MVC). After MVC, the number of motor unit spikes/second needed to maintain this posture was about 50% less than prior to MVC. Surface rectified integrated EMG activity declined in parallel to the decline in spike counts. To determine whether different muscles were compensating for the reduction in spike counts, synergistic muscles were examined simultaneously. Similar reductions were noted. In one deafferented subject, EMG activity increased rather than decreased after MVC . Fatigue decreases the contraction-relaxation rate of muscle fibers, which lowers fusion frequency. Thus, lower rates of motor unit activation can result in the maintenance of constant force. A feedback system from muscle to CNS likely senses this slowing and leads to the spike count reduction. PMID- 2266988 TI - Schwartz-Jampel syndrome with dominant inheritance. AB - The Schwartz-Jampel syndrome (SJS) is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces, skeletal deformities, joint contractures, short stature, muscle hypertrophy, clinical myotonia, and continuous muscle fiber activity. The inheritance pattern of SJS has been assumed to be autosomal recessive. We report the occurrence of the classic SJS syndrome in both a father and son in a non-consanguineous family, suggesting that SJS has the potential for a dominant pattern of inheritance. PMID- 2266989 TI - Carpal tunnel syndrome: correlations between pressure measurement and intraoperative electrophysiological nerve study. AB - In 19 carpal tunnel syndrome (CTS) patients and 4 control subjects a catheter was introduced into the carpal tunnel and slowly retracted in 5 mm steps. Pressure was measured with the continuous infusion technique. In the same group of patients and controls, median nerve antidromic sensory action potential (aSAP) was detected intraoperatively stimulating proximally (S1), in the center (S2), and distally (S3) to the carpal tunnel and recording from the third finger (R). Sensory conduction velocity (SCV) and aSAP amplitude were considered in S1-S2, S2 S3 and S3-R segments. The intracarpal tunnel pressure was significantly higher in CTS patients than in controls, with the highest values located between 25 and 35 mm distal to the proximal border of the flexor retinaculum. SCV and aSAP amplitude were also decreased most often in the distal part (S2-S3) of the carpal tunnel. PMID- 2266990 TI - Randomized, double-blind trial of mazindol in Duchenne dystrophy. AB - There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy. PMID- 2266991 TI - Vector short-latency somatosensory-evoked potentials after median nerve stimulation. AB - A new method has been developed for recording short-latency somatosensory-evoked potentials after median nerve stimulation. Negative electrical forces recorded with three orthodiagonal bipolar electrodes in the neck had a direction opposite to that of impulse conduction in the proximal peripheral and cervical somatosensory pathway. Sequential tracings of vectors opposite the electrical forces were made in three-dimensional display, thus reproducing the actual time sequence of electrical events in those structures. Fixed generators such as the subcortical nuclei were also analyzed with this technique, and multiple generators of N13 potential (N13a and N13b) were visualized. This technique may be useful in the functional evaluation of the somatosensory pathway in the cervical cord. PMID- 2266992 TI - Neurogenic muscle weakness in chronic progressive external ophthalmoplegia (CPEO) PMID- 2266993 TI - Steroid-responsive microvasculitis in polymyalgia rheumatica. PMID- 2266994 TI - Delayed postradiation focal motor neuron syndrome. PMID- 2266995 TI - Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis. PMID- 2266996 TI - Muscle & Nerve: Index to volume 13. PMID- 2266997 TI - Melanin as a virulence factor in pathogenic fungi. AB - The pigment melanin is found universally in nature and is attributed to a variety of functions. In some fungi it is thought to play a decisive role in the determination of virulence. This review examines the experimental evidence which has led to an understanding of the mechanisms by which melanin functions in pathogenic fungi, particularly in plant pathogens, in Cryptococcus neoformans and Wangiella dermatitidis. PMID- 2266998 TI - Molecular genetics of pathogenic fungi: some recent developments and perspectives. AB - The diagnosis and the treatment of fungal diseases remains problematic in many cases. Difficulties in diagnosis are due (1) to the ubiquitous presence of fungal pathogens that may lead to false positive test results and (2) to difficulties in the evaluation of the aetiological significance of these pathogens. The relatively small number of effective antifungal agents reflects to a large extent on the fact that many aspects of fungal physiology and virulence are not well understood. The methods of molecular genetics provide effective tools for the diagnosis of mycoses and may also contribute to the identification of new targets for antifungals by genetic analyses of fungal virulence. During the last 3 years molecular genetic methods have been developed for the asexual pathogen Candida albicans that may be used for strain identification. This success indicates a general use of molecular genetics for the analysis of fungal pathogenesis. PMID- 2266999 TI - Sporotrichosis in the metropolitan area of Cusco, Peru, and in its region. AB - Eight cases of sporotrichosis originating from the metropolitan area of Cusco, Peru, and its region are described, including the circumstances of infection and the isolation of Sporothrix schenckii from the lesions. This finding classifies this particular area with high altitude, low temperature and dry weather as an endemic zone of interest in the epidemiological and ecological study of Andean sporotrichosis. Among the eight cases observed, five were of the fixed cutaneous type and three were lymphocutaneous. Six patients were male and two female. Two paediatric cases were also observed. Therapy with potassium iodide was very satisfactory, whereas poor results were obtained with ketoconazole. PMID- 2267000 TI - Subcutaneous mucormycosis caused by Mucor hiemalis Wehmer f. luteus (Linnemann) Schipper 1973. AB - The authors report a case of subcutaneous mucormycosis in a diabetic patient with verrucous lesions in the fourth finger of the right hand. Initially diagnosed as a fixed cutaneous sporotrichosis case, success was obtained with the use of potassium iodide with healing of the lesion in a period of nearly 5 months. At present the patient remains under clinical observation with no treatment or relapse. PMID- 2267001 TI - Malassezia pachydermatis isolation from a scarlet macaw. AB - A repeated isolation of Malassezia pachydermatis Weidman from a scarlet macaw is reported. This is the first report of birds infected with this yeast. PMID- 2267002 TI - Liposomal amphotericin B treatment in a 9-month-old liver recipient. AB - A 9-month-old boy with a suggested candidemia was treated with liposomal amphotericin B (AmBisome, Vestar) after a liver transplant due to an inherited glycogenosis (Pompe's disease). This is believed to be the youngest patient in which this new therapeutic agent has been utilized. PMID- 2267003 TI - Growth of Candida albicans on the stratum corneum of diabetic and non-diabetic patients. AB - We have used a novel approach to in vitro culture of Candida albicans on cyanoacrylate skin surface strippings. It appears that with this model yeasts and hyphae grew on large surfaces of stratum corneum. The area of extension of the fungal growth was larger on stratum corneum taken from diabetic than from non diabetic volunteers. PMID- 2267004 TI - In vitro antifungal activities of new imidazole salts towards dermatophytes. AB - The in vitro activities of two new miconazole and econazole salts with the sulphosalicylic acid against 71 clinical isolates of dermatophytes were evaluated in comparison with those of miconazole, miconazole nitrate, econazole and econazole nitrate. Miconazole sulphosalicylate and econazole sulphosalicylate were equally effective in inhibiting the fungal growth compared with miconazole, econazole, and their nitrates. PMID- 2267006 TI - Interactions between proteins, peptides and amino acids. New advances 1986-1989. AB - The paper deals with the recent achievements in the study of the various interactions between proteins, peptides and amino acids. The interactions are classified according to the hydrophilic, hydrophobic or mixed character of the interactive forces. The effect of the interaction on protein (peptide) association, structure and biological activity as well as the role of individual amino acid residues in the hydrophobic and hydrophilic interactions are discussed. PMID- 2267005 TI - Effect of dehydrated apple products on the serum and liver lipids in Syrian hamsters. AB - The effect of two dehydrated apple products (10% in diet)--apple pulp (crude fibre 3.5%, pectin 1.4%) and apple pomaces (crude fibre 13.5%, pectin 7%)--on the serum and liver lipids of growing Syrian male hamsters were studied. The animals were fed a natural diet (38% of energy substituted by milk fat; the diet contains 53 mg of cholesterol (CH) per 100 g) which resulted in an accumulation of CH and triacylglycerols (TG) in the serum as well as in the liver, and CH-rich very low density lipoproteins (VLDL) in the circulation. After two months both apple products decreased the levels of CH and TG in serum (by 40-70%) and the content of CH in VLDL with similar efficiency. Both products reduced CH content in the liver, and the apple pulp also decreased TG content. Up to the 6th month the apple pulp studied suppresses accumulation of CH and TG in both the serum and the liver. A complete analysis of lipoproteins of main density class at the time showed that the decrease of serum CH and TG to a decisive extent is due to the decrease of their concentration in VLDL (by more than 50%). Therefore, the concentration of VLDL and the whole lipoprotein pool decreased by 50%. The apple pulp doubled the amount of CH transported by HDL. Three months after the replacement of butter in the diet by corn germ oil the CH and TG levels in the serum and TG also in the liver decreased to the physiological level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267007 TI - [Progress report. What can one expect from a "functional prenatal toxicology?"]. AB - In the strategy of investigation applied and demanded in prenatal toxicology partial aspects have been overstressed until now, although here as well as in postnatal toxicology the problems should be viewed in its complexity (in this case, F1-generation in its several pre- and postnatal stages of development). Therefore, there was the urgent need to summarize the existing methods of functional investigation in the field of prenatal toxicology and to compare them with conventional morphological methods as to their meaningfulness and sensitivity. As a result, the routine introduction of clinical-functional investigations is demanded. PMID- 2267008 TI - Research finding on smoking of abused substances. PMID- 2267009 TI - Clinical pharmacology of inhaled drugs of abuse: implications in understanding nicotine dependence. PMID- 2267010 TI - Pyrolysis and inhalation studies with phencyclidine and cocaine. PMID- 2267011 TI - Animal models of drug self-administration by smoking. PMID- 2267012 TI - The pharmacology of cocaine smoking in humans. PMID- 2267013 TI - Current patterns of drug abuse that involve smoking. PMID- 2267014 TI - Effects of habitual use of marijuana and/or cocaine on the lung. PMID- 2267015 TI - Pyrolytic degradation of heroin, phencyclidine, and cocaine: identification of products and some observations on their metabolism. PMID- 2267016 TI - "Nursing in the nineties". PMID- 2267017 TI - Infant observation. PMID- 2267018 TI - More on assessment! PMID- 2267019 TI - Re-examining the nursing process: Part 2. Patient assessment--the basis of care. PMID- 2267020 TI - Obstetrics in seventeenth century England. PMID- 2267021 TI - AIDS community awareness: aspects of an evolving campaign. PMID- 2267022 TI - Formative and summative evaluation in perspective. Part I. PMID- 2267023 TI - AIDS test for surgery patients demanded. PMID- 2267024 TI - [What does the future require of nurse administrators in private hospitals?]. AB - Specialisation inside a modern private hospital is on the increase with important implications for the nurse administrator of today. A change in objectives for effective services and quality care to meet population needs is required. The nurse administrator should give attention to important aspects like leadership styles, loyalties, services, technology and specialised knowledge. PMID- 2267025 TI - An interview with Carol A. Lockhart. Interview by Carmella A. Bocchino. AB - In early summer, Nursing Economic$ had the opportunity to discuss with Carol A. Lockhart, PhD, RN, FAAN, her thoughts on the Physician Payment Review Commission (PPRC), the implications of PPRC's work for nursing, the nation's failing health care system, and managed care. PMID- 2267026 TI - Wages & benefits of nursing personnel in nursing homes: correcting the inequities. AB - The nursing home industry is an increasingly important component of long-term care. Yet major problems in access and quality are evident. Correcting the inadequate wages and benefits of nursing home personnel is a necessary first step in addressing this issue. PMID- 2267027 TI - ICU nurse-physician collaboration & nursing satisfaction. AB - ICU nurses who are satisfied with their work are more likely to be retained, leading to institutional cost savings. In this study, higher levels of nurse physician collaboration in making decisions about patient care were found to be very important to nurses' satisfaction. PMID- 2267028 TI - Newer compensation practices for the nurse executive. AB - Today's health care leaders must be prepared differently and have a different set of expectations in their roles. More creative approaches to assuring both commitment and productivity, such as tying rewards to performance and personal accomplishment, are emerging. PMID- 2267029 TI - An educational loan repayment program for registered nurses. AB - A state-sponsored loan repayment program offers nurse executives a unique and highly effective recruitment and retention strategy while providing financial assistance to professional nurses repaying educational loans. PMID- 2267030 TI - Impact of federalism on the state legislature. AB - The concept of federalism has been through numerous machinations and continues to evolve as our nation grows and matures. Legislators at all levels and the public must decide which level of government can best mandate, administer, and pay for health care. PMID- 2267031 TI - Communicating in the 1990s: a technology update. AB - With the variety of available technologies, choosing among them will be difficult at best. Waiting for integration and standardization among technologies may effectively eliminate a competitive edge and productivity improvements for health care organizations. Also, selecting which one communication technology is needed may not be the issue since several technologies likely are needed to solve different communication needs in organizations. One might begin to sort out options by performing an assessment of current communication patterns and deficiencies. Ideally, the assessment should be completed by someone who is able to assess needs over an entire organization, not just one service or one organizational level. The assessment should focus at least on some of the following questions. Are three major problems with staff or client communications? If staff-related, are primary needs interactive with routine communication needs? If they are interactive, time-sensitive, and inter organizational then a form of video-conferencing may help. Short-term interactive needs might be met by leasing video-conferencing rooms. Long-term, time sensitive interactive needs might require PC-based video-conferencing, Non-time-sensitive, interactive, inter-organizational needs might be met with voice mail or e-mail, which allow some time-delayed but single-mode interactions. If communication needs are routine, one might examine how e-mail, or fax could help. If text-based paper traffic through the mail room is enormous or slow, e-mail may help. If communication among persons at any level of geographically separate organizations is needed, modem-based or public e-mail may be the answer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267032 TI - The gallbladder in room 405. PMID- 2267033 TI - Changing verbal abuse into a syntonic interactive mode: the nurse manager's challenge. PMID- 2267034 TI - Patient care automation: the future is now. Part 4: From philosophy to implementation. AB - Computer systems that meet the five principles and support the nine attributes detailed above are most likely to provide optimized operational support to all providers, enhancing efficiency, efficacy and quality of health care. Each time one feature is not included, providers must substitute by decreasing the quality of care delivered, and/or by increasing the quality of care delivered, and/or by increasing the clerical work needed to manage the care system. PMID- 2267035 TI - A strategic nursing assistance program--SNAP. PMID- 2267036 TI - Arguments with nursing & technology column. PMID- 2267037 TI - Brochure explains how National Practitioner Data Bank differs from ANA's Nurses Claims Data Base. PMID- 2267038 TI - AIDS update. PMID- 2267039 TI - [Peripheral and spinal pathways involved in diffuse inhibitory controls induced by noxious stimulation. Neurosurgical approach in rats]. AB - Electrophysiological recordings were made from spinal and trigeminal dorsal horn convergent neurones which allowed the investigation of some mechanisms underlying Diffuse Noxious Inhibitory Controls (D.N.I.C.) to be made. These controls are exclusively triggered by the activation of A delta and/or C peripheral fibres and involve a supraspinal loop. The ascending and descending parts of the looped pathway are confined within the anterolateral quadrants and the posterolateral funiculi respectively. PMID- 2267040 TI - [Endovascular treatment of intracranial aneurysms. Value and prospects based on a series of 92 cases]. AB - Endovascular treatment of intracranial aneurysms is a recent technique which needs to be evaluated in large series. From 1978 to 1988, 92 cases of aneurysms were balloon-treated at Lariboisiere Hospital either by parent vessel occlusion (O.V.P.) (N = 48) or by selective obliteration (O.S.A.). Treatment in all but 5 cases was performed 3 weeks after S.A.H. since the main reason for choosing endovascular technique was contraindication of early surgery. Giant aneurysms account for 31 cases, vertebro-basilar for 38 and cavernous carotid for 27. In O.V.P. group, there were 17 patients referred after subarachnoid hemorrhage and 30 after tumoral symptoms, while in O.S.A. group, 30 bled and 5 presented with oculomotor palsies. Results in the O.V.P. group are good with 8% morbidity and mortality. In O.S.A., they are worse: 16% (morbidity and mortality) and 22% of secondary balloon deflation; however, because of the features of these aneurysms (size and location), the results seem quite acceptable. Endovascular treatment of intracranial aneurysms is a promising technique which should already replace parent vessel ligation when indicated, and progressively supplant surgical clipping when the remaining technical problems are resolved. PMID- 2267041 TI - [Transcranial Doppler in the evaluation of vasospasm after subarachnoid hemorrhage]. AB - Flow velocities (F.V.) in 65 patients admitted for subarachnoid hemorrhage (S.A.H.) were measured 4-7 times a week by Transcranial Doppler (T.C.D.). Patients were classified into 4 T.C.D. groups according to the highest mean flow velocity recorded in the M.C.A. during hospitalization: Group 1 (18 patients) with F.V. below 100 cm/s (normal), group 2 (19 patients) with F.V. between 100 150 cm/s (starting spasm), group 3 (23 patients) with F.V. between 150-200 cm/s (major spasm) and group 4 (5 patients) with F.V. over 200 cm/s (critical spasm). Based on clinical, radiological and ultrasound data as well as patient outcome (good results with no specific problems or with transient deficit, permanent deficit and pre- or postoperative death), the authors analyse the value of T.C.D. in the evaluation of vasospasms following S.A.H. The review involves 49 patients with surgically treated aneurysms (including two associated A.V.M.s), 9 patients who had suffered a S.A.H. of unknown origin and 7 patients who had died prior to surgery. T.C.D. is a non-invasive method of following post-S.A.H. spasms and the close correlation between the angiography and the T.C.D. makes pre-operative control angiographies unnecessary. A correlation between clinical status and T.C.D. was only observed in extreme cases where F.V. exceeded 200 cm/s or increased by 100 cm/s or more within 3 days (6 patients out of 65). M.C.A. spasm can, however, be underestimated by the T.C.D. approach in cases where there is an associated spasm of the infraclinoidal carotid artery. In these cases, classical Doppler evaluation of the cervical portion of the I.C.A. is indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267042 TI - [Aneurysms with severe clinical manifestations (Hunt and Hess grade IV and V). A series of 66 cases]. AB - Among 250 patients consecutively admitted in our center with a ruptured intracranial aneurysm, 66 patients (24.4%) were initially classified in Hunt and Hess clinical grade IV (37 cases) or grade V (29 cases). All patients were studied as following: --The severity of subarachnoid haemorrhage was evaluated on the pre-operative C.T. scan using Fisher's criteria. Quantification of the intracerebral haematoma or the intraventricular associated haemorrhage or a subdural haematoma was estimated as well. --The arterial diameter, aneurysm size and location, and the eventual presence of intra-arterial embolus were noted on the pre-operative angiography. Aneurysm location was: anterior artery 27 cases, internal carotid artery 9 cases, middle cerebral artery 27 cases, posterior cerebral artery 2 cases, and 1 case on the basilar artery. In this series, a poor clinical condition on admission was related to the direct effect of the initial haemorrhage in 84.9% of the patients. Early seizures (7.6%) acute hydrocephalus (1.5%), multiple emboli (3%) and apparently early diffuse vasospasm (1.5%) were the other documented causes explaining the initial poor clinical condition. One case remained completely unexplained. Sixteen patients admitted with bilateral fixed dilated pupils or a major intracerebral haematoma from a ruptured anterior artery aneurysm were not operated on and subsequently died. Operative treatment (aneurysm clipping in all cases, and haematoma evacuation on demand) was performed in the remaining 50 cases within 12 hours after their admission. Thus, these patients underwent surgery on Day 0 in 31 cases, on Day 1 in 11 cases, and on Day 2 in 8 cases. A post-operative C.T. scan was performed in 46 cases. Post operative angiographic control was only performed in 29 cases. Changes on the post-operative C.T. scan or the angiographic control were strictly compared to the neuroradiological information previously available. Final outcome was assessed at least two months after the onset. According to the Glasgow Outcome Score, the results were: good recovery 12 patients (18.2%); moderate disability 1 patient; severe disability 4 patients (6%); vegetative state 4 patients; death 45 patients (68.2%). Excluding the patients admitted in poor clinical grade but presenting with early seizures or minor initial haemorrhage, the mortality rate was 74.2%. According to the initial clinical grade, the initial C.T. scan findings, the eventual post-operative angiographic presence of an arterial thrombosis or vasospasm, it was obvious that the final bad outcome was mainly related to the severity of the initial haemorrhage. However, in 7 patients, post operative disability or death can be explained by other complications, principally an arterial thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267043 TI - [Surgery of the radiculo-spinal cord junction in the treatment of chronic pain and incapacitating spasticity. Report of a series of 29 patients]. AB - This series involves 29 patients treated for chronic pain (9 patients) or severe spasticity (20 patients). The surgical technique used was the microsurgical D.R.E.Z.-tomy technique as described by Sindou. In the first group, three patients had malignant pain, while the six others had deafferation pain. In the second group, spasticity involved the upper limb in 13 patients and the lower limbs in 7 patients. Out of 20 patients, one-third suffered from cerebral palsy. In the first group, results one year after surgery were excellent or good in 7 out of the 9 patients. In the group treated for spasticity, a significant decrease in spastic disorders was observed in 16 of the 20 patients over a 1 to 4 year follow-up period. There was also an improvement of voluntary movements in 11 patients and a decrease in pain in 15 patients belonging to this group. A number of complications were noted: cerebrospinal fluid leakage in two cases, painful anesthesia in the C5 to T1 territory in one case, transient paresis of the upper limb in six cases. One patient died as a result of an expansive pneumatocele (3.4% of cases). PMID- 2267044 TI - [Opticochiasmatic apoplexy]. AB - A 26-year-old patient presented with acute chiasmal syndrome. Computerized Tomography and Magnetic Resonance Imaging demonstrated an intrachiasmal hematoma which was evacuated via a right subfrontal approach. Histological examination revealed an arteriovenous malformation. In 21 similar cases in the literature, surgery generally resulted in the improvement of ophthalmological signs. In 3/4 of the cases, histology identified a subjacent lesion (arteriovenous malformation, cavernoma, venous angioma, glioma). PMID- 2267045 TI - [Long-term survival after surgery of solitary cerebral metastasis of lung cancer. Clinical case and review of the literature]. AB - In cases of solitary brain metastasis of lung cancers other than small cell lung carcinoma, which has an even poorer prognosis, long-term patient survival over 1.2 years is rare. One case with a 12 year survival is presented. The authors review the other 18 cases with a minimum 5 year survival described in the literature. It is concluded that surgical aggressivity is justified in these cases. PMID- 2267046 TI - [Development of intracerebral hydatid cyst evaluated with x-ray computed tomography. A case report]. AB - In a study of a double cerebral hydatic cyst developed in a patient operated for another intracranial neurosurgical affection, the authors have determined the rate of growth of these cysts by repeated C.T. scan examinations. This rate was 4.5 cm a year, a value which is higher than other values classically accepted. PMID- 2267047 TI - [The value of anterior plate fixation without bone graft in simple luxation and various fracture-luxations of the lower cervical spine]. AB - In comparison to posterior fixation by Roy-Camille plates which does not require bone grafting, the authors present 9 cases of anterior plate fixation, also without bone grafting (6 dislocations and 3 fracture-dislocations of the lower cervical spine). The results and indications of this technique are discussed. PMID- 2267048 TI - Anastomoses among the perforating arteries of the brain. Microanatomy and clinical significance. AB - Anastomoses among the perforating arteries were examined in 50 human brains using injection technique with India ink and gelation, or methylmethacrylate. Anastomoses were not found among the perforators of the internal carotid artery and the thalamogeniculate branches. Anastomotic channels involving perforating branches of the anterior choroidal, middle cerebral, and anterior cerebral arteries were noted in 1% of the cases. Vascular connections of the premamillary arteries were observed in 30% of the brains. They varied from 60 to 280 microns) in diameter, and from 0.3 to 3.6 (mean 1.5 mm) in length. Anastomoses among the interpeduncular (thalamoperforating) branches of the posterior cerebral artery were present in 79% of the cases. They ranged from 80 to 400 microns (mean 146 microns) in caliber, and from 0.9 to 6.1 mm (mean 3.3 mm) in length. Since anastomoses among the interpeduncular and the premamillary arteries are much more frequent than those among other perforators, thalamic, subthalamic, and midbrain's infarctions seem to be less frequent than capsular and ganglionic ischemic lesions. PMID- 2267049 TI - [Hepatolenticular degeneration]. AB - Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results. PMID- 2267050 TI - Primary trigeminal neuralgia (algophoric deafferentation hypersensitivity syndrome). AB - In the article the author presents his theory of the pathogenesis of primary trigeminal neuralgia, explaining the occurrence of this mysterious disease by algophoric deafferentation hypersensitivity. Tooth extraction is the sole cause of algophoric deafferentation hypersensitivity, which, culminating in epileptiform discharges of the trigeminal nociceptive pathway neurons, leads to clinical features of characteristic neuralgic paroxysms. Trigger mechanism is explained by ephaptic transmission between the broken fibers for phasic pain of the tooth pulp and neighbouring fibers of epicritic and proprioceptive sensitivity. The typical occurrence of periods with remission of neuralgic paroxysms the author explains by his original theory of biorhythms neogenesis with the involvement of two antagonistic neural subsystems (nociceptive and antinociceptive system). The concept is based on indisputable clinical, anatomical, pathoanatomical, experimental and pharmacologic facts, which the author quotes as the contribution to his theory. PMID- 2267051 TI - The effect of piracetam on the somatosensory evoked cortical potentials in the course of both carotid arteries obstruction. AB - Nootropics are psychoactive substances that activate, protect and restore functions of the neuronal cells. Piracetam is the first representative of these compounds, often cited to act as an activator and protector of neuronal cells function, especially in hypoxic conditions. Therefore, we examined the effect of piracetam on the cortical neuronal activity in conditions when both carotid arteries have been ligated. We assumed that oligaemia occurred as the result of arterial obstruction and consequent hypoxic state developed. Evoked somatosensory potentials were used as an objective indicator of neuronal cells functional state. Our results demonstrate that the occlusion of both carotid arteries induces the extension of latency and reduction of the amplitude in the somatosensory evoked potentials of the adult cat. Piracetam (100 mg/kg i.v.) improves the evoked potentials returning both, latencies and amplitude to the control values, i.e. as measured before the ligature of arteries has been settled. Regarding a number of papers claiming that piracetam facilitates cholinergic neurotransmitter system, and that the amplitude of the somatosensory evoked potentials is increasing depending on the amount of the acetylcholine released, we think that the effect of piracetam on the evoked potentials during the occlusion of both carotid arteries, registered in our experiments, is mediated through the action of piracetam on the cholinergic system. PMID- 2267052 TI - Open study of sustained-release formulation of levodopa and benserazide in parkinsonian patients. AB - The efficacy of a novel oral sustained-release preparation of levodopa/benserazide (Madopar HBS) was compared to that of previous conventional levodopa/benserazide treatment in 15 patients with idiopathic Parkinson's disease and with severe fluctuations in motor response to long-term levodopa therapy. In ten patients who suffered from clear-cut "end-of-dose" deterioration, significant benefit was obtained on HBS form, while 5 patients did not respond well to the new levodopa preparation. Plasma levels of levodopa were more stable with HBS compared to conventional levodopa preparation in our patients, although doses of HBS form required for an optimal response averaged 1.48 times that of previous conventional levodopa. PMID- 2267053 TI - Basic relations among lesion laterality, lesion volume and neuropsychological performance. AB - Although it is widely accepted that lesion size is an important determinant of severity of deficit, difficulties in the quantification of lesion size and the absence of a theoretical model of how lesion volume combines with lesion locus to produce deficits have inhibited the development of methodological and statistical procedures for studying naturally occurring lesions in humans. We propose such a unified model and apply it to the analysis of neuropsychological performance in a sample of patients with naturally occurring unilateral lesions. The analysis suggests that a statistical interaction between lesion size and laterality may be an important determinant of neuropsychological deficit. PMID- 2267054 TI - Planning and spatial working memory following frontal lobe lesions in man. AB - Twenty-six patients with unilateral or bilateral frontal lobe excisions were compared with age and IQ matched controls on a computerized battery of tests of spatial working memory and planning. A computerized test of spatial short term memory capacity revealed no significant impairment in the patients' ability to execute a given sequence of visuo-spatial moves. In contrast, a paradigm designed to assess spatial working memory capacity, revealed significant impairments in the patient group in both possible types of search errors. Furthermore, additional analysis showed that the frontal lobe patients were less efficient than controls in their usage of a strategy for improving performance on this test. Higher level planning was also investigated using a test based on the "Tower of London" problem [SHALLICE, T. Phil. Trans. R. Soc. Lond. B. 298, 199 209, 1982]. Patients with frontal lobe damage required more moves to complete the problems and a yoked motor control condition revealed that movement times were significantly increased in this group. Taking both of these factors into consideration, initial thinking (planning) time was unimpaired in the patient group although the thinking time subsequent to the first move was significantly prolonged. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of an impairment of higher cognitive functioning following frontal lobe damage. PMID- 2267055 TI - Implicit learning of new faces in prosopagnosia: an application of the mere exposure paradigm. AB - A prosopagnosic patient was shown faces with which he had no prior experience, and was then given two-alternative forced choice recognition ("which of these faces did you see before?") and preference ("which of these faces do you like better?") tasks to assess learning. The patient showed normal preference for target faces, despite the fact that recognition of the faces was nil. This suggests that at least some prosopagnosics show implicit learning of new faces. The patient's normal preference for target faces is conceptualized as a "perceptual fluency" effect similar to that seen in more global forms of amnesia. PMID- 2267056 TI - Individual variation in line bisection: a study of four patients with right hemisphere damage and normal controls. AB - In a previous study of line bisection, [Manning et al., Neuropsychologia 28, 647 655, 1990] we have shown that normal young adults show significant linear regressions of both transection displacement (TD) and standard deviation (SD) on line length. Furthermore, there was considerable individual variation in the magnitude of SDs and the direction and magnitude of TDs. These two sources of variance were uncorrelated. In the current study we provide a constructive replication of these findings on an older population that constitutes a more appropriate control sample for patients with stroke. The performance of four patients with right hemisphere stroke is then interpreted in terms of the constraints observed in normal subjects. All the patients showed qualitatively intact line bisection, but with quantitative impairments of varied severity. When analysed in two pairs, the patients also showed a double-dissociation between the magnitude of their mean transection displacements and the SDs of those means. This result is in conformity with the prediction based upon a lack of correlation between these two measures in normal subjects. PMID- 2267057 TI - Development of visual field advantage for digit and random shape recognition: comparison of cross-sectional and longitudinal studies. AB - The visual field advantage for digits and random shapes recognition was investigated using both longitudinal and cross-sectional methods with children from ages from 4 to 6. A right visual field advantage for digit recognition and left visual field advantage for random shape recognition were found in the age 4 group. There was no evidence of developmental increase in visual field advantage with age, though there was slight gender difference in the development of visual field advantage. Comparisons of the results of longitudinal and cross-sectional methods revealed negligible differences. PMID- 2267058 TI - Sex differences in cognitive abilities: a cross-cultural perspective. AB - Studies in Western cultures have indicated significant sex differences in certain cognitive abilities. To determine whether similar differences occur in a non Western culture, this study administered a cross-linguistic battery of tests to high school students in Japan and America. In both cultures, girls averaged significantly higher scores on a Story Recall test, the Digit-Symbol test and a Word Fluency test whereas boys achieved significantly higher scores on a Mental Rotation test. The analysis of standardized test scores further indicated that the size of the sex difference was culture-independent in three out of these four cases. These results are discussed in the context of the GESCHWIND and GALABURDA [Cerebral Lateralization, Biological Mechanisms, Associations and Pathology, Bradford Books, Cambridge, Massachusetts] account of the contribution of testosterone to left-right asymmetries in early cerebral development. PMID- 2267060 TI - Integration of visual information and motor output in reaching and grasping: the contributions of peripheral and central vision. AB - This study examined the contributions made by peripheral and central vision to reaching and grasping. A specially designed contact lens system was used to restrict information to the peripheral retina. Modified goggles were used to restrict information to the central retina. A WATSMART motion analysis system was used to record and reconstruct three dimensional kinematic data. Analyses included an examination of peak kinematic values as well as a qualitative description of the trajectory profiles as related to transport and grasp components. With only peripheral vision, information related to size and shape of an object was inadequate, thus affecting the organization of both the transport and grasp components. With only central vision, information related to the location of an object was inadequate, affecting the organization of the transport but not the grasp component. Implications are discussed relevant to the current models of visuomotor control of reaching and grasping. PMID- 2267059 TI - Priming effects in a letter-by-letter reader depend upon access to the word form system. AB - Several types of cognitive and neuropsychological evidence suggest that priming effects on such implicit memory tests as word identification are mediated by a pre-semantic visual word form system that can operate independently of episodic memory. We investigate priming in a letter-by-letter reader, P.T., whose pattern of performance on neuropsychological tests indicates preservation of the word form system. Experiment 1 revealed robust priming on a word identification test following letter-by-letter study of target words, despite P.T.'s great difficulty in identifying non-studied words. Experiment 2 showed that the priming effect was modality specific whereas Experiment 3 indicated that recall of previously studied words was not modality specific, thus indicating that the observed priming could not be attributed to explicit memory strategies. Experiment 4 revealed no priming of illegal nonwords on a letter identification test. The results support the notion that priming on the word identification test depends on access to the word form system. PMID- 2267061 TI - Mouth asymmetry during speech of epileptic patients who have undergone carotid amytal testing. AB - Asymmetry in the opening of the two sides of the mouth during speech has been suggested as an observable correlate of lateralization of cerebral speech motor control. For 24 epileptic patients who suffered speech disturbance only during left hemisphere carotid amytal anesthetization, 22 showed the expected greater opening of the right side of the mouth during a repetition task. However, all four of the patients who suffered speech disturbance following only right hemisphere anesthetization, and 8 of the 11 "bilateral speech" patients, also showed greater opening of the right side of the mouth. The speech dominant patients may, however, have genetic left speech dominance but a pathology-forced shift of some components of language to the right hemisphere. Basic mouth asymmetry, as measured here, may primarily reflect lateralization of a component of the motor/speech/language control system that may not be shifted by pathology in epileptic patients sustaining early brain insult. Relative change in mouth asymmetry as the speech task becomes more demanding may, however, be a more sensitive indicator or cerebral asymmetries for language in pathological cases. PMID- 2267062 TI - Damaged pride. PMID- 2267064 TI - Isolating the cause of hypotension. PMID- 2267063 TI - Silently hurting. PMID- 2267065 TI - Prednisone therapy for patients with asthma. PMID- 2267066 TI - Just say yes. PMID- 2267068 TI - From A to Z: tips & time-savers for career development, Part 2. PMID- 2267067 TI - How to help foreign nurses adapt. PMID- 2267069 TI - Reaching out to Mrs. Cooper. PMID- 2267070 TI - A question of inadequate documentation. PMID- 2267071 TI - When children have A.I.D.S.: how to support the family. PMID- 2267072 TI - Recognizing and managing cholelithiasis. PMID- 2267073 TI - Focus on arfonad. PMID- 2267074 TI - Preventing hypothermia during fluid resuscitation. PMID- 2267075 TI - Action stat! Spinal cord injury. PMID- 2267076 TI - Low blood pressure. How to investigate this ominous sign. PMID- 2267078 TI - How to safely draw blood from a vascular access device. PMID- 2267077 TI - Why nurses & doctors should be partners in diagnosis. PMID- 2267079 TI - Evelyn had plans--and they didn't include dying. Nursing grand rounds. PMID- 2267080 TI - The secret torment of Mrs. Panaretis. PMID- 2267081 TI - What's causing your patient's respiratory distress? PMID- 2267082 TI - How to lend support in a crisis. PMID- 2267084 TI - A.I.D.S. Time to grieve. PMID- 2267083 TI - Nurses' GI handbook. PMID- 2267085 TI - A loving will. PMID- 2267086 TI - Nothing of value. PMID- 2267087 TI - A Christmas for Michael. PMID- 2267088 TI - Lidocaine alert: beware of hooded syringes. PMID- 2267089 TI - Amantadine for influenza A. PMID- 2267090 TI - Administering S.C. heparin. PMID- 2267091 TI - A.I.D.S. dilemma. Keeping quiet. PMID- 2267092 TI - Cerebrovascular accident. What you need to know. PMID- 2267093 TI - Confronting substance abuse. PMID- 2267094 TI - Action stat! Hypothermia. PMID- 2267095 TI - Detecting life-threatening arrhythmias. PMID- 2267096 TI - Some nurses can pronounce death. PMID- 2267097 TI - New drugs. PMID- 2267098 TI - Assessing a pregnant woman after trauma. PMID- 2267099 TI - Preventing pressure ulcers. How to recognize and care for patients at risk. PMID- 2267100 TI - The trouble with Ryan. PMID- 2267101 TI - Myths & facts ... about chronic wound care. PMID- 2267102 TI - Determining the cause of nausea and vomiting. PMID- 2267103 TI - Making frustration work for you. PMID- 2267104 TI - Preparing for staff-development sessions. PMID- 2267105 TI - Choosing a lay smear taker. PMID- 2267106 TI - Cultural safety. PMID- 2267107 TI - Ear trouble. PMID- 2267108 TI - GP contracts--more than meets the eye. PMID- 2267109 TI - Peace of mind. PMID- 2267110 TI - Graduation blues. PMID- 2267111 TI - Nursing data: more than just numbers. PMID- 2267112 TI - Coroner's cases. PMID- 2267113 TI - Cardiac stress testing without the use of exercise. PMID- 2267114 TI - 111In-antimyosin antibody imaging for detection of myocardial infarction: a quantitative approach. AB - Indium-111-antimyosin imaging has been shown to be a sensitive and specific method for detecting myocardial necrosis, but a quantitative method for interpretation of 111In-antimyosin planar images is lacking. A prospective study was performed in 114 patients with suspected acute myocardial infarction using planar 111In-antimyosin imaging. A ratio of maximum myocardial uptake counts (H) (9 X 9 pixels) over adjacent lung background (L), i.e. H/L ratio, was obtained from 24 and 48 h images. This value was compared with peak creatine kinase (CK) enzyme and left ventricular ejection fraction (LVEF). The patients were classified into groups based upon standard criteria for Q-wave acute myocardial infarction (Q-MI) (n = 50), non-Q-MI (n = 21), unstable angina (n = 15) and those with no evidence of MI or ischaemia (n = 28). The mean +/- S.D. H/L ratio in the Q-MI group was 2.28 +/- 0.50 (24 h, left anterior oblique, LAO, view) and was greater than the non-Q-MI group (1.98 +2- 0.30) (P less than 0.02). In patients with unstable angina (UA), seven had a high ratio (1.75 +/- 0.29) and eight had a lower ratio (1.29 +/- 0.07). In the group of patients without MI or UA, the ratio was 1.24 +/- 0.11 and this was significantly lower than the Q-MI and non-Q-MI groups and those patients with UA and positive 111In uptake (P less than 0.001, respectively). However, there was no significant difference between old MI and patients without evidence of MI or UA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267115 TI - Estimation of right ventricular pressure by 201Tl scintigraphy in paediatric cardiac disease. AB - To estimate right ventricular overload in paediatric cardiac disease, 201Tl scintigraphy was used to quantify right ventricular uptake. Six methods for calculating the 201Tl right-to-left ventricular uptake ratio (TRL) were compared, based on the location of regions of interest (ROIs), use of total count or mean count density, and the ROI-based method or profile method. When the TRL was compared with the right-to-left ventricular peak systolic pressure ratio (RVP/LVP), the mean count density method using entire right and left ventricular ROIs seemed to be appropriate, considering its simplicity, reproducibility and regression line. The linear regression line was RVP/LVP = 1.15 x TRL - 0.13 (n = 15, P = -0.0001), and RVP(mm Hg) = 162 x TRL - 33 (n = 15, P = 0.0001). In four patients with pulmonary stenosis, the changes of TRL were in good agreement with the right ventricular pressure changes after percutaneous balloon valvuloplasty. Thus, evaluation of thallium scintigraphy using this quantitative method can be a simple and effective way to evaluate patients with right ventricular pressure overloading. PMID- 2267116 TI - Technique for the use of standard outlines for attenuation correction and quantification in SPECT. AB - A technique is described for using a set of standard outline images for attenuation correction and quantification in SPECT. The effectiveness of the method was investigated using an anatomical phantom and in a series of 123I-mIBG patient imaging studies. In the latter measurements the ability of the technique to quantify the activity of various features in the images was compared to the use of CT images for attenuation correction. The mean difference between the two measurements was 4.4%. PMID- 2267117 TI - Effect of food and activity on the reproducibility of isotopic GFR estimation. AB - The reproducibility of the plasma clearance of 99Tcm DTPA was studied in 26 patients under standardized conditions with the subject fasting and at rest. The coefficient of variation of duplicate measurements in patients with glomerular filtration rates (GRF's) ranging from 11-103 ml min-1 was 8%. Mean GFR following a breakfast containing 670 kcal and 31 g protein was increased significantly from 40.7 +/- 28.1 ml min-1 to 43.6 +/- 30.8 ml min-1. When fasted but permitted free exercise there was no consistent trend in GFR but the coefficient of variation of duplicate estimates increased significantly to 12.1%. It is recommended that routine GFR measurement should be carried out fasting or following a light diet with restricted activity. PMID- 2267118 TI - Late biodistribution of 99Tcm macroaggregates for lung perfusion imaging. PMID- 2267119 TI - Poor binding efficiency using 99Tcm-labelled HSA. PMID- 2267120 TI - Decision making in nursing. PMID- 2267121 TI - Correlation of family dynamics and boundaries in three to five year old children. PMID- 2267122 TI - [Ultrasonic follow up of spontaneous regression of neonatal abdominal cystic changes]. AB - Abdominal cyst was diagnosed in 14 babies by ultrasound examination (9 multicystic dysplastic kidneys, 4 ovarian cysts, 1 bowel duplication). The cysts were followed up in 6 patients by ultrasound, and marked reduction of multicystic dysplastic kidneys was observed in 2 patients, and 1 ovarian cyst was disappeared. Their experience and a review of the literature suggest that conservative management with sonographic reevaluation is an acceptable alternative to surgical therapy in uncomplicated cases. PMID- 2267123 TI - [Intra-partum ethamsylate (dicynone) administration in the prevention of cerebral hemorrhage in premature infants]. AB - Dicynone has been in use in all premature births prophylactically since 1987 by the authors. The administration of the drug begins before or during delivery. The diagnoses of cerebral haemorrhage was established on autopsy and the cases were compared with the previous years when Dicynone was not administered. During prophylactic use of Dicynone the cerebral haemorrhages significantly reduced among premature babies. It is well known, that the etiology of the cerebral haemorrhages are multifactorial. Their favourable experiences confirm the literary communications, whereas use of Dicynone can be one of the efficacious preventive drug against palsy of the premature babies. PMID- 2267124 TI - [Possibilities of lymphoscintillography in head and neck surgery (II): results of clinical evaluation]. AB - In order to determine the value of lymphoscintigraphy the clinical results were compared to the lymphoscintigraphic findings. The latter were further compared to the histological results and to the isotope activity of single lymph nodes. The examination was performed in 31 cases of head and neck malignancies before neck dissection (in 29 cases radical neck dissection was done because of palpable lymph nodes; in 2 further cases elective neck dissection was performed on the NO neck). Lymphoscintigraphy yielded evaluable results in 28 cases. Lymphoscintigraphy correlated with the clinical results in 21 cases. Lymphoscintigraphy, histopathology and clinical examination showed correlation in 19 cases. Further application of head and neck lymphoscintigraphy is warranted. PMID- 2267126 TI - [The physician and the emperor (Dr. Zimmermann at the bedside of Frederick the Great)]. PMID- 2267125 TI - [Public health aspects of the Martin-Bell syndrome]. AB - A carrier mother has eleven children. Of 5 boys, four are affected by Martin-Bell syndrome. Of 6 girls, four were found carrier. Authors summarise the medical genetic characteristics of this syndrome which is the second most common genetic cause of mental retardation. PMID- 2267127 TI - [Forensic medical investigation of the Katyn mass graves]. PMID- 2267128 TI - [Diagnosis of rupture of the ventricular septum as a result of myocardial infarct]. PMID- 2267129 TI - [Ethical codes of animal experiments]. PMID- 2267130 TI - N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18). AB - We have recently identified and cloned the gene for a cytosolic polypeptide, designated oncoprotein 18 (Op18), which is expressed in acute lymphocytic leukemia and some solid tumors including neuroblastoma. Op18 is phosphorylated upon treatment of lymphoid cells with phorbol myristate acetate. We have proposed that unphosphorylated Op18 plays a role in cellular proliferation, and that its phosphorylated forms, namely Op18a and Op18b, are associated with diminished cell proliferation. In this study, we report that in neuroblastoma tumors, the phosphorylation of Op18 was substantially diminished with increasing N-myc gene copy number. Treatment of the neuroblastoma cell line SMS-KCNR, which contains 75 copies of the N-myc gene, with retinoic acid for ten days resulted in an increase in Op18 phosphorylation. Our findings provide evidence for distinct patterns of Op18 phosphorylation in neuroblastoma tumors with and without N-myc gene amplification. PMID- 2267131 TI - Expression of cellular-yes protein in mammalian tissues. AB - Expression of the c-yes proto-oncogene in normal mammalian tissues was studied by immunohistochemistry and by immunoprecipitation assays using affinity purified anti-yes IgG. The antibody was raised against the amino-terminal domain of the human c-yes protein expressed in bacteria as a trpE-yes fusion protein. We detected p62c-yes in a variety of rat and human tissues but its relative level of expression varied significantly among different cell types. Certain epithelial cells, platelets and spermatid acrosomes showed the highest levels of p62c-yes. Intracellular localization of p62c-yes in epithelial cells differed among organs performing different physiological functions. The overall pattern of expression suggests that p62c-yes may be involved in numerous cellular pathways. PMID- 2267132 TI - Suggestive evidence for functionally distinct, tumor-suppressor genes on chromosomes 1 and 11 for a human fibrosarcoma cell line, HT1080. AB - One approach for identifying chromosomes which carry putative tumor-suppressor genes is the introduction of specific chromosomes into the tumor cells of interest. We examined the ability of human chromosomes derived from normal fibroblasts to suppress or modulate tumorigenicity in nude mice and the in vitro properties of HT1080, a human fibrosarcoma cell line. We first isolated mouse A9 cells containing a single human chromosome (1, 2, 7, 11, or 12) integrated with pSV2neo plasmid DNA. Following fusion of microcells from these A9 cells with the HT1080 cells, clones that were resistant to G418 were isolated and karyotypically analysed. Three of 4 microcell-hybrids with an introduced chromosome 1 were non tumorigenic (#1-7, -8 and -13), whereas the parental HT1080 cells were highly tumorigenic. The other microcell-hybrid clone (#1-1) formed tumors, the cells of which had lost one copy of chromosome 1. Two clones from the #1-1 cells were isolated; one contained an extra copy of chromosome 1, and the other one did not. The former was non-tumorigenic and the latter was tumorigenic. The introduction of chromosome 11 also suppressed the tumorigenicity of HT1080 cells, while the introduction of other chromosomes, i.e., 2, 7, or 12, had minimal or no effect on the tumorigenicity of these cells. Cells from tumors formed by microcell-hybrids with the introduction of chromosome 2, 7, or 12 still contained the introduced chromosome. Interestingly, only the microcell-hybrids with an introduced chromosome 1 had an alteration in cellular morphology and modulation of in vitro transformed properties, i.e., cell-growth and saturation density in a medium containing 10% calf serum and cell-growth in soft-agar. Thus, the results indicate the presence of putative tumor-suppressor genes for HT1080 cells on chromosomes 1 and 11, and further suggest that the genes on these chromosomes control different neoplastic phenotypes. PMID- 2267133 TI - Oncogenes in multiple myeloma: point mutation of N-ras. AB - Alterations of ras, c-myc and bcl-1 have been described in hematologic malignancies of lymphoid origin. We investigated the structure of these genes and evaluated the frequency of point mutations involving H-, K- or N-ras in bone marrow samples from patients with multiple myeloma. No abnormalities were detected in the c-myc and bcl-1 genes, but two of 17 patients were found to have N-ras mutations by differential oligonucleotide hybridization and dideoxynucleotide sequencing following amplification by polymerase chain reaction. Bone marrow DNA from both patients had identical missense mutations of N-ras codon 61 changing CAA to AAA, resulting in a substitution of lysine for glutamine in the encoded protein. Multiple myeloma is the first mature B cell neoplasm found to harbor ras mutations. PMID- 2267134 TI - Chromatin alterations surrounding the BCR/ABL fusion gene in K562 cells. AB - Chronic myelogenous leukemia (CML) is characterized by the presence of a novel fusion gene comprised of portions of the BCR gene from chromosome (ch) 22 and the ABL gene from ch 9. The present study was designed to identify regulatory DNA regions as determined by DNAase I hypersensitivity to address the question of whether altered chromatin contributes to changes in ABL expression. We identify five hypersensitive (HS) sites within the abnormal BCR/ABL allele in K562 cells in a pattern different from the normal BCR. The pattern of hypersensitivity is modified when the cells undergo hemin induced differentiation. These results indicate that the normal BCR has a chromatin configuration consistent with active transcription and that the BCR/ABL fusion gene chromatin is different. This may be important in the pathogenesis of CML. PMID- 2267135 TI - Cell cycle control by p53 in normal (3T3) and chemically transformed (Meth A) mouse cells. I. Regulation of p53 expression. AB - In addition to controlling the transition of resting normal cells from the G0 state of the cell cycle into S-phase, expression of the cellular protein p53 also seems to be necessary for the proliferation of cycling normal cells in an as yet undefined manner. To further elaborate the role of p53 in growing cells, we analysed p53 expression and its regulation in cells going into, and after release from, growth arrest at the restriction point (R-point) in the G1-phase of the cell cycle, induced by isoleucine depletion. Since growth arrest at the R-point is subject to internal control mechanisms of the cell cycle, this approach allowed us to include in our analyses normal Balb/c 3T3 fibroblasts, as well as cells of the chemically induced Balb/c fibrosarcoma cell line Meth A, expressing mutated p53. Isoleucine depletion induced a viable growth arrest at the R-point in cells of both cell lines, marked by a synchronous shut-down of DNA synthesis when the cells went into growth arrest, and a synchronous resumption of DNA synthesis after a lag period of about 2-4 h when the cells were released from growth arrest, as well as a shift to a G1 DNA content at the R-point. p53 expression in both cell lines showed a phenotypically similar regulation, as its synthesis was specifically reduced at the R-point. At the molecular level, however, p53 expression in growth arrested 3T3 cells was controlled at the transcriptional/post-transcriptional level, whereas control in growth arrested Meth A cells seemed to be at the level of mRNA translation. After release from growth arrest, p53 synthesis in both types of cells was rapidly restored, preceding resumption of total protein synthesis, and exhibiting a p53-specific profile. PMID- 2267136 TI - Cell cycle control of p53 in normal (3T3) and chemically transformed (Meth A) mouse cells. II. Requirement for cell cycle progression. AB - To further characterize the role of p53 in growing normal Balb/c 3T3 fibroblasts, as well as of p53 in cells of the methylcholanthrene induced fibrosarcoma cell line Meth A, we analysed the effect of inhibition of p53 synthesis by microinjection of p53-specific monoclonal antibody PAb 122 into the nuclei of these cells after release from growth arrest induced by isoleucine starvation (see preceding paper [Steinmeyer et al., this issue] ). We show that microinjection of PAb 122, but not of control immunoglobulins, into the nuclei of both types of cells effectively blocked their re-entry into the S-phase of the cell cycle. Since isoleucine depletion of these cells was shown to lead to a growth arrest at the restriction point (R-point) in the G1-phase of the cell cycle, our results (i) define more precisely the role of p53 in growing cells as a protein controlling transition of the cells through this restriction point, and (ii) demonstrate that mutated p53 in Meth A cells still is functional with regard to cell cycle control at this restriction point. We suggest that p53 acts as a 'gate-keeping' protein at restriction points in the cell cycle, exerting a positive effect on the transition of cells through the cell cycle. PMID- 2267137 TI - Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. AB - The expression of p53, a transformation associated protein, has been found to be regulated during the cell cycle. We show here that the subcellular localization of p53 varies throughout the cell cycle. In growth stimulated Balb/c 3T3 cells, p53 is produced at elevated levels and the newly synthesized protein accumulates in the cytoplasm during the G1 phase. Around the beginning of the S phase, p53 accumulates in the cell nucleus, where it stays for about 3 h. Following this initial step of DNA synthesis, p53 is no longer found in the nuclear compartment, but rather accumulates in the cytoplasm. This modulation in the subcellular localization of p53 suggests that the protein is spatially regulated during cell cycle. PMID- 2267138 TI - Increased retinoblastoma gene expression is associated with late stages of differentiation in many different cell types. AB - The retinoblastoma (Rb) gene is a recessive oncogene or tumor-suppressor gene whose inactivation leads to the development of tumors. Recently, evidence pointing to a role for the Rb gene in the differentiation of certain human cell types has been presented. We have studied three mouse cell lineages to determine whether there is a correlation between Rb gene expression and differentiation. We find that induction of mouse erythroleukemia cell differentiation with either dimethylsulfoxide (DMSO) or hexamethylene bisacetamide (HMBA) leads to increased expression of Rb mRNA. Increased expression of Rb mRNA was also found in S2 myoblasts induced by mitogen depletion to become differentiated myotubes. In the B-cell lineage, Rb expression is low in pre-B and B cell lines but high in plasmacytomas, which represent late stages of B cell differentiation. Thus, in all three lineages (erythroid, muscle, and B-cell) late stages of differentiation are associated with increased amounts of Rb mRNA. PMID- 2267139 TI - Career changes: finding your "ideal job". PMID- 2267140 TI - At first blush. PMID- 2267141 TI - Amodal representation of occluded surfaces: role of invisible stimuli in apparent motion correspondence. AB - A series of demonstrations were created where the perceived depth of targets was controlled by stereoscopic disparity. A closer object (a cloud) was made to jump back and forth horizontally, partially occluding a farther object (a full moon). The more distant moon appeared stationary even though the unoccluded portion of it, a crescent, changed position. Reversal of the relative depth of the moon and cloud gave a totally different percept: the crescent appeared to flip back and forth in the front depth plane. Thus, the otherwise-robust apparent motion of the moon crescents was completely abolished in the cloud-closer case alone. This motion-blocking effect is attributed to the 'amodal presence' of the occluded surface continuing behind the occluding surface. To measure the effect of this occluded 'invisible' surface quantitatively, a bistable apparent motion display was used (Ramachandran and Anstis 1983a): two small rectangular-shaped targets changed their positions back and forth between two frames, and the disparity of a large centrally positioned rectangle was varied. When the perceived depths supported the possibility of amodal completion behind the large rectangle, increased vertical motion of the targets was found, suggesting that the amodal presence of the targets behind the occluder had effectively changed the center position of the moving targets for purposes of motion correspondence. Amodal contours are literally 'invisible', yet it is hypothesized that they have a neural representation at sufficiently early stages of visual processing to alter the correspondence solving process for apparent motion. PMID- 2267142 TI - Motion aftereffects from a motionless stimulus. AB - Dimming or brightening regions superimposed, slightly out of register, on static light or dark blobs, give rise to apparent motion. When these regions are replaced by apparent brightening or dimming produced by ramp aftereffects, a directional motion aftereffect is perceived. It is concluded that filters sensitive to temporal derivative signals of net brightening or dimming provide an input into the motion pathways. PMID- 2267143 TI - Mueller-Lyer decrement: practice or prolonged inspection? AB - Noting the similarity between the illusion decrement and selective adaptation paradigms, Long has challenged the view that illusion decrement effects reflect a strategic--as opposed to a structural--underlying mechanism, and has called for further research on this issue. To investigate the confound between prolonged free inspection and repeated trials in the standard decrement procedure, the effects of three inspection conditions (continuous, intermittent, and immediate) on the magnitude of the overestimation Mueller-Lyer illusion have been assessed under two levels of trials (a total of two or six judgments). Significant illusion decline was found only under conditions of repeated trials, with either continuous or intermittent inspection. These findings do not support the predictions of purely structural theories (including neural adaptation and efferent readiness theories), according to which degree of decrement should be determined solely by viewing time. Instead, the data demonstrate that illusion decrement is a product of practice, providing converging evidence for the view of decrement as involving a cognitive 'recalibration' or learning process. PMID- 2267144 TI - Operation Desert Shield: a call to duty for nurses. PMID- 2267145 TI - Moral development and unethical student behaviors. PMID- 2267146 TI - Nurses' job satisfaction in mental health and neuro-sciences setting. PMID- 2267147 TI - The plight of non-smokers and the nurses' responsibility. PMID- 2267148 TI - Tuberculosis. PMID- 2267149 TI - Organizing a short-term course on maternal and child health nursing. PMID- 2267151 TI - Selectivity--a new trend within primary health care. PMID- 2267150 TI - Reach out and touch.... PMID- 2267152 TI - Major issues confronting the nursing profession. PMID- 2267153 TI - Nursing: past, present and future. PMID- 2267154 TI - Nursing services in Orissa. PMID- 2267155 TI - International Nurses' Day: May 12, 1990. Theme: nurses and the environment. The roles of nurses' associations and individual nurses in promoting health by safeguarding the environment. PMID- 2267156 TI - Pituitary adenoma: a case study. PMID- 2267157 TI - What every family and community has a right to know about diarrhoea. PMID- 2267159 TI - OSCE: an experience in first-aid examination of nursing students. PMID- 2267158 TI - Emerging challenges in nursing education. PMID- 2267160 TI - Emerging challenges in nursing services in the hospital: a panel discussion. PMID- 2267161 TI - Nutrition for mother and child. PMID- 2267162 TI - Status of health in India and its future prospects. PMID- 2267163 TI - Environmental sanitation in an urban field area: a report. PMID- 2267165 TI - The importance of community's participation in nursing programmes. PMID- 2267164 TI - Infant weaning. PMID- 2267166 TI - A preliminary blueprint: Central Institute of Nursing. PMID- 2267167 TI - Nursing education and administration today and tomorrow. PMID- 2267168 TI - Treatment and care in leprosy. PMID- 2267169 TI - Status of health in India and its future prospects. PMID- 2267170 TI - [Diagnostic value of the lupus band test in patients treated by chronic hemodialysis]. AB - The diagnosis of systemic lupus erythematosus in cases with advanced renal failure is a serious clinical problem. The purpose of the study was an analysis of the incidence of various non-renal criteria (according to ARA) for the diagnosis of SLE in patients with chronic renal failure of various aetiology and find out whether the lupus band test in these patients may serve as an additional criterion for the diagnosis of SLE. The studied group comprised 39 patients with chronic renal failure (28 men and 13 women) aged 17-58 years. In this group 29 cases were treated with dialyses and 10 conservatively. The most frequent clinical sign (apart from renal changes) accepted as diagnostic criteria for the SLE was polyserositis and leucopenia and thrombocytopenia. In no case antinuclear antibodies, antibodies against DNA and against soluble nuclear antigens were found. Positive LBT was obtained in 72.4% of cases with chronic renal failure, particularly frequently in the dialysed patients. A positive result of the LBT cannot be of decisive importance in the diagnosis of SLE but may suggest a need of more detailed investigations (determination of Ro antibodies) for confirmation of the diagnosis. PMID- 2267172 TI - [Cigarette smoking and the pathophysiology of diseases of the digestive system- facts and hypotheses. II. The role of cigarette smoking in the pathogenesis of digestive system diseases]. PMID- 2267171 TI - [Effect of hemodialysis fluids with different pH values and buffer types used in peritoneal dialysis on the phagocyte system in the peritoneal cavity. The experimental part]. AB - In a four-hour exchange of dialysing fluid in 120 healthy mice it was checked whether and in what degree changes of the pH of the dialysing fluid in the range from 5.09 to 7.02 and change of the buffer in the dialysing fluid (acetate, lactate) have an effect on the phagocytic and bactericidal ability of the phagocytic cells in the peritoneal dialysate. The study of the count of phagocytic cells, their bactericidal ability (NBT test) and phagocytosis ability (latex test) showed that neither the type of the used buffer nor pH changes of the dialysing fluid in the range 5.09-6.18 had no effect on the defensive properties of the phagocytes in healthy peritoneal cavity. The observation of a statistically significant increase in the proportion of cells of low phagocytic ability in the group of mice receiving acetate buffer of pH 7.02 requires further studies. PMID- 2267173 TI - [Corticosteroids in the treatment of chronic active hepatitis]. PMID- 2267174 TI - [Treatment of acute hepatic failure]. PMID- 2267175 TI - [Effect of the autonomic nervous system on liver function in physiological and various pathological conditions]. PMID- 2267176 TI - [Diagnostic difficulties in hepatic amyloidosis--clinical analysis and autopsy data of 3 cases]. AB - Three patients with amyloidosis in whom hepatomegaly was the main sign ara presented. In all cases jaundice coexisted which is regarded as a rare sign in amyloidosis. Attention is called to the diagnostic difficulties of amyloidosis especially without a preceding clinically overt disease process. The presence of a particularly high activity of alkaline phosphatase in the serum, and focal absence of 99Tc uptake by the hepatic macrophage system in liver scintigram suggested liver tumour. However, demonstration of monoclonal protein in blood, urine or ascitic fluid, or raised level of alpha 2 globulin, should call attention to the possibility of liver amyloidosis. The authors stress the usefulness of the method of preincubation of tissue biopsy specimens in potassium hypermanganate during routine staining with Congo red for differentiation of amyloid AA from amyloid AL. PMID- 2267178 TI - The slowdown in the infant mortality decline. PMID- 2267177 TI - [Lavage of the whole lung in a patient with pulmonary alveolar lipoproteinosis]. AB - The first in Poland procedure of whole lung lavage is reported. The patient had intravitally diagnosed pulmonary alveolar lipoproteinosis. Difficulties in an effective and safe performance of the procedure are discussed. Modernized methods of lung lavage in patients with severe respiratory failure due to pulmonary alveolar lipoproteinosis are described. PMID- 2267179 TI - Birthweight and infant mortality: perceptions and pitfalls. PMID- 2267181 TI - Fumes from the spleen. PMID- 2267180 TI - Poverty, technology and recent trends in the United States infant mortality rate. PMID- 2267182 TI - So what? Last of a dying breed. PMID- 2267183 TI - Home accidents to children under 2 years of age. AB - Within a population-based register of childhood injuries, 641 home accidents to children aged under 2 years were recorded in six hospitals. The annual rate was higher in children over 1 year (6.6 per 100) than in infants (2.7 per 100). A male predominance was observed only after the first birthday. Most injuries were related to physical trauma (mainly falls), but burns and poisonings were frequent in the second year. Most lesions were benign, except in the case of falls from a height (from a window or baby furniture). Nineteen per cent of the children were admitted to hospital. There were 15 skull fractures, two fatal cases and two severe sequelae. Child abuse was seldom suspected and the reasons for this are discussed. The study of the circumstances in which accidents occur leads to the conclusion that the main aspect of prevention should be passive protection ensured by the creation of a safe environment (compulsory safety standards for baby furniture, child resistant packaging), but that parents' information and education should also be developed, with emphasis on knowledge of children's normal psychological and motor development and abilities. PMID- 2267184 TI - The development of a model for predicting infants at high risk of sudden infant death syndrome in Tasmania. AB - A statutory 'Notification of Birth' form, containing obstetric and perinatal information, has been routinely collected for Tasmanian deliveries since 1974. For the period 1980 to 1984, birth notification data was collected for over 99% of Tasmanian deliveries. This data was examined for the 130 cases of sudden infant death syndrome (SIDS) that occurred from 1980 to 1984 and for 610 controls. It was then used to construct an at-birth scoring system to predict infants at higher risk of SIDS in the postneonatal period. A predictive model of the relative risk of SIDS was developed by fitting a binomial/logistic generalised linear model to the binary 1980-1984 case control data with birth variables used as predictors. The final predictive model contained five variables (maternal age, infant sex, birth weight, month of birth and feeding practice) and had a sensitivity of 62% and specificity of 73%. The model was then tested on independent birth cohorts from 1985 and 1986 and found to have a sensitivity of 47% and specificity of 77%. The risk of SIDS in the group of infants classified as high risk was 7.9 per 1000 live births and in the group at low risk it was 2.5 per 1000 live births. In addition, the model predicted 74% of neonatal deaths occurring during these 2 years. This compares well with other predictive models developed elsewhere. The predictive model will be used to identify infants at high risk for SIDS in a prospective cohort study. PMID- 2267185 TI - Maternal supplementation and bone growth in infancy. AB - The effects of maternal supplementation during pregnancy and lactation on bone growth of infants were investigated in 272 mother-infant pairs who participated in the Guatemalan Longitudinal Study of Nutritional Supplementation, Growth and Development. Mothers received one of two nutritional supplements according to village of residence, and bone growth was determined from dimensions of the second metacarpal measured directly from hand-wrist radiographs of 3-month-old infants. Multiple regression analyses indicated significant supplementation effects on cortical bone dimensions related to the volume of supplement intake. These findings were independent of maternal characteristics and attendance at the supplementation centres, and the infant's gender, size, gestational age and morbidity experience. The nutrient composition of the supplements and the patterns of the supplementation effects eliminate proteins, energy, calcium and phosphorus as the nutrients potentially responsible for the bone-specific response. Candidate nutrients for the observed effects are vitamin A, ascorbic acid, niacin, thiamin, iron or fluorine. Presumptive evidence suggests the effects may be due to vitamin A supplementation. These findings suggest opportunities for nutritional intervention in pregnancy and the early postpartum period to prevent osteopaenia in infancy. PMID- 2267186 TI - The prevalence and characteristics of congenital pigmented lesions in newborn babies in Oxford. AB - Melanocytic naevi (MN) are recognised risk factors for malignant melanoma but the epidemiology of MN is poorly understood. Some MN are present at birth and the study of congenital lesions is an important first step toward understanding the development of MN in early life. In this study, the prevalence and characteristics of congenital pigmented lesions were documented in 1012 White caucasian newborn babies at a maternity hospital in Oxford. Only 12 babies (1.2%) were found to have pigmented skin marks and each of these had only one lesion and no other abnormalities. MN were identified with certainty in only five babies (0.5% of the population; 95% CI, 0.06%-0.93%) thus confirming the relatively low prevalence of this lesion. Four of the MN were noted to be 'small' (less than 15 mm diameter) and all five were less than or equal to 20 mm in diameter. In other respects, the MN displayed a diversity of features. Of the other lesions there were two Mongolian blue spots, one melanocytic pustule, one 'probable' MN and three unusual skin marks where the diagnosis was uncertain but considered unlikely to be MN. During the course of the study, examinations were also carried out incidentally on 39 non-White babies. Twenty-two of these were noted to have Mongolian spots (57%) and three had other pigmented lesions (8%). PMID- 2267187 TI - Invasive Haemophilus influenzae infections among children in Rochester, Minnesota: a population-based study. AB - The incidence of invasive Haemophilus influenzae infections was studied among all residents of Rochester, Minnesota, under 20 years of age during the period 1975 1983. The incidence in children under 5 years of age was 115 and 64 cases per 100,000 children per year for all invasive cases and for meningitis, respectively. These rates are among the highest reported for an essentially all Caucasian population in the United States, while the ratio of meningitis to non meningitis cases (1.1:1) is among the lowest. This suggests possible under ascertainment of non-meningitis cases in previous US studies of Haemophilus influenzae infections. PMID- 2267188 TI - Childhood risk factors for ischaemic heart disease and stroke. AB - To explore the relation between environmental influences in early life and risk of cardiovascular disease in adulthood, case-control comparisons were made on 99 patients with acute myocardial infarction and 55 patients with recent hemisphere stroke. After allowance for smoking habits and current social class, risk of myocardial infarction was higher in subjects of lower social class at birth, smaller stature, and with a history of infant and especially perinatal death in a sibling. Stroke was also associated with infant or perinatal death in a sibling. Although none of these associations was statistically significant at a 5% level, they support other evidence that implicates the pre and early postnatal environment in the aetiology of cardiovascular disease. PMID- 2267189 TI - Landfill waste disposal: an environmental cause of childhood cancer? PMID- 2267190 TI - [Controversies and progress in the treatment of multiple myeloma]. PMID- 2267191 TI - [Trial application of transfection tests in feasibility studies for transforming DNA in white blood cells of patients with chronic lymphatic leukemia]. AB - Transfection technique with the use of high molecular DNA was applied for the investigations of peripheral blood white cells DNA transforming properties in patients with chronic lymphatic leukemia B. Using transfection tests in liquid medium (focus assay) and colony forming in soft agar, the differences in L(tk-) cells transformation were noted following an addition of neoplastic DNA. Medium collected over transformants has shown mitogen properties in micro-mitogen tests on cells BALB/c 3T3. No correlation between clinical stage of the disease and the results of tests was observed. PMID- 2267192 TI - [Assessment of the efficacy of treating infections in hematopoietic proliferative diseases: Monotherapy with ceftazidime and tobramycin combined with amoxycillin/ampicillin]. AB - Efficacy of the ceftazidime monotherapy in 120 febrile children with neoplastic diseases and granulocytopenia was compared with that of tobramycin combined with amoxycillin/ampicillin. The obtained results were similar in both types of antibiotic therapy. However, granulocytopenia was higher and septicemia was more frequent in children treated with ceftazidime. Isolated bacteria were more sensitive to ceftazidime than to tobramycin with amoxycillin/ampicillin. Both regimens were tolerated well. Despite a low number of patients in both groups, one may conclude that ceftazidime is more efficient in patients with granulocytopenia. Less adverse reactions, lower number of infections, less frequent medical procedures, elimination of the potentially toxic aminoglycosides and lower cost of therapy advocate the use of ceftazidime monotherapy. PMID- 2267193 TI - [Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. AB - The efficiency of antiemetic drugs was investigated in 36 children with neoplasia (mainly of hematopoietic system) in the course of 83 cycles of chemotherapy. The following antiemetic drugs were investigated: Fenactil (brand of chlorpromazine), Torecan (brand of thienylpromazine maleate), Aviomarin (brand of dimenhydrinate), Decadron (brand of dexamethasone), Primperan (brand of metoclopramid), and placebo. The most efficient was dexamethasone which prevented vomiting in 54% cycles of chemotherapy and diminished their intensity in the remaining cycles. No adverse reactions were noted. Efficacy of Fenactil, Torecan, Aviomarin, and Primperan was similar to that of placebo. PMID- 2267194 TI - [Clinical pharmacology of pentostatin]. PMID- 2267195 TI - [Deficit of glucose phosphate isomerase in erythrocytes of a Polish girl with inherited hemolytic anemia]. PMID- 2267196 TI - [Successful treatment of meningeal involvement in Hodgkin's disease in a child]. AB - Meningeal involvement was diagnosed in a child with IVB degree Hodgkin's disease following three alternatives cures with MVPP/B-DOPA. Irradiation of the skull with alternative intrathecal injections of drugs were applied. The treatment was completed 16 months after the diagnosis of meningeal involvement. No symptoms are observed. PMID- 2267197 TI - [Use of cyclosporin A in the treatment of Sezary's syndrome]. AB - A case of Sezary's syndrome treated with Cyclosporin A is reported. A cutaneous improvement without haematological effect was observed. PMID- 2267198 TI - [Progress in the treatment of advanced neuroblastoma]. PMID- 2267200 TI - The photic sneeze. PMID- 2267199 TI - Antiphospholipid antibodies: which and when? PMID- 2267201 TI - Weight change, perceived health status and mortality in middle-aged British men. AB - The association between weight change over a 5-year period, the subsequent perception of health and the mortality during a 4-year follow-up period has been examined in a prospective study of 7735 middle-aged British men. There were 357 deaths from all causes. Self-assessment of health status was considered as a potential guide to whether weight loss was intended or involuntary. Irrespective of weight change those who reported poor or fair health had a more than two-fold increase in death rate compared to those who reported good or excellent health. Considerable weight gain (greater than 10%) was associated with high rates of cardiovascular disease regardless of health perception, although this was most marked in those who perceived poor or fair health. Moderate weight gain was of little importance except in those who regarded their health as poor or fair. Weight loss was associated with increased death rates from cancer regardless of health perception, although the rates were highest in those who perceived poor or fair health. This study emphasizes that weight loss is a potentially serious symptom even in men who report good health. Assessment of weight change and of perception of health status are both of value and could be used in standard health enquiries to monitor health status in individuals and the community. PMID- 2267202 TI - Immobilization-related hypercalcaemia--a possible novel mechanism and response to pamidronate. AB - Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome. PMID- 2267203 TI - Typhoid hepatitis. AB - Liver involvement in typhoid fever is uncommon. Typhoid hepatitis is now being recognized as a definite entity. Over a period of 4 years, we have observed 10 cases (4.8%) of typhoid hepatitis out of 210 cases of typhoid fever. Jaundice, anaemia, hepatomegaly and abnormal biochemical tests were present in all cases. Liver biopsy was done in 8 cases and was found to be abnormal in 5. Two of the 10 cases of typhoid hepatitis died. Recognition of typhoid hepatitis is important since it has to be differentiated from other common ailments in the tropics such as viral, malarial or amoebic hepatitis. Early institution of specific therapy in cases of typhoid hepatitis carries a good prognosis. PMID- 2267204 TI - Upper gastrointestinal bleeding--when to operate. PMID- 2267205 TI - Therapeutic implications of diastolic dysfunction in heart failure. PMID- 2267206 TI - Superadded aspergillosis on carcinoid bronchial adenoma leading to delayed diagnosis. AB - A review of aspergillosis in neoplastic disease revealed that most cases occur in association with malignant disorders. Amongst solid tumours it is mostly adenocarcinomas which are invaded by the fungus due to necrotic cavity formation. We here record the first reported association of aspergillosis with a benign carcinoid bronchial adenoma which was hidden by the fungal growth with a delay in diagnosis. PMID- 2267207 TI - Withdrawal of maintenance digoxin from institutionalized elderly. AB - Chronic use of digitalis is common amongst the institutionalized elderly. Associated with digitalis use is the potential for toxicity and/or adverse reactions. In this study maintenance digoxin was withdrawn from 14 elderly nursing home residents in sinus rhythm. Subjects were followed over 18 months for evidence of dysrhythmia or heart failure. One resident had an episode of supraventricular tachycardia which required digoxin to be restarted. One resident developed left heart failure, treated with oral diuretic. For 12 of the 14 residents, withdrawal of maintenance digoxin was achieved without deleterious effect. This study suggests that maintenance digoxin may be withdrawn safely in elderly nursing home residents in sinus rhythm and without history of atrial dysrhythmia. PMID- 2267208 TI - Go North young woman--a look at Finnish specialist training. PMID- 2267209 TI - Pulmonary varix--pathognomonic appearance. PMID- 2267211 TI - Coarctation of the aorta associated with a sinus venosus atrial septal defect presenting with endocarditis in middle age. AB - We report the case of a 44 year old man who presented with an infective endocarditis and was found to have a coarctation of the aorta associated with a sinus venosus atrial septal defect and a small ventricular septal defect. The association of coarctation with a sinus venous atrial septal defect presenting with endocarditis in an adult is extremely rare. PMID- 2267210 TI - Submandibular chronic sialadenitis presenting with alcohol-induced pain. AB - A 32 year old man with alcohol-induced pain over a right submandibular swelling is described. Excision biopsy of this swelling revealed chronic sialadenitis and the symptoms promptly ceased following this excision. We speculate on the possible pathophysiological mechanism. PMID- 2267212 TI - Thrombotic thrombocytopenic purpura with terminal pancytopenia. AB - A 27 year old housewife developed thrombotic thrombocytopenic purpura during the twelfth week of pregnancy. She had partial response to initial plasma infusion and subsequent plasmapheresis. However, her clinical course was complicated by the development of severe pancytopenia the consequence of a hypocellular marrow. She succumbed to septicaemic shock one month after diagnosis. The development of hypocellular marrow in thrombotic thrombocytopenic purpura has not been reported before. PMID- 2267213 TI - Histiocytic cytophagic panniculitis. AB - A 33 year old man developed fever, malaise, jaundice, pancytopenia, coagulation abnormalities, hepatomegaly, pleural effusions and a subcutaneous lump. Biopsies revealed a lobular panniculitis with the presence of cytophagic histiocytes; erythrophagocytosis was also demonstrated in the liver and bone marrow. Despite the use of chemotherapy (CHOP) his clinical condition deteriorated and he died 5 months after presentation. This illness is consistent with the recently described syndrome of histiocytic cytophagic panniculitis. PMID- 2267214 TI - Nemaline myopathy: a report of two siblings as evidence of autosomal recessive inheritance of the infantile type. AB - We report two opposite-sex siblings with the severe infantile form of nemaline myopathy; diagnoses were made on muscle biopsy. Neither parent showed clinical or electromyographic evidence of myopathy, and both had negative muscle biopsies. Autosomal recessive inheritance seems likely. PMID- 2267215 TI - Spontaneous pyelo-jejunal fistula. AB - This case report describes a patient with a spontaneous jejunal fistula. This is a rare type of nephro-intestinal fistula with only two previously recorded similar cases. Our patient presented with such a fistula diagnosed by antegrade pyelography, associated with a staghorn calculus and proven at surgery. The value of antegrade pyelography is discussed along with the treatment options and the outcome to be expected in such patients. PMID- 2267216 TI - Hepatic infarction: an unusual complication of nephrotic syndrome in a patient with diabetes mellitus. AB - A 67 year old woman with widespread atherosclerosis and diabetic nephropathy manifested by nephrotic syndrome and moderate renal failure developed multiple hepatic infarctions. The infarctions were documented by computed tomographic scan and needle aspiration biopsy of the liver. Except for the nephrotic syndrome and the atherosclerosis no other cause of hepatic infarction was found. We suggest that hepatic infarction should be considered in the thrombotic complications of the nephrotic syndrome secondary to diabetic nephropathy. PMID- 2267217 TI - Spontaneous rupture of a splenotic nodule. AB - A case is presented of spontaneous rupture of splenic tissue occurring 14 years after a splenectomy was carried out for trauma. Spontaneous rupture of a splenotic nodule has not previously been described and it may be added to the list of causes of spontaneous haemoperitoneum. The incidence and function of residual splenic tissue are briefly discussed and other causes of splenic rupture are outlined. PMID- 2267218 TI - Conversation piece--the medical publisher. Interview by P.D. Welsby. PMID- 2267219 TI - Pentoxifylline in septic shock. PMID- 2267220 TI - Hypoglycaemia and atrial fibrillation. PMID- 2267221 TI - Inappropriate secretion of vasopressin, hypopituitarism and corticosteroid therapy. PMID- 2267223 TI - Study of unlicensed personnel who provide assistance to the nurse. PMID- 2267222 TI - Phaeochromocytoma presenting with acute intestinal ischaemia and shock. PMID- 2267224 TI - Health policy development: how to become involved. PMID- 2267225 TI - Determinants of parental decisions to abort for chromosome abnormalities. AB - Parental decisions concerning the continuation of pregnancy following prenatal detection of abnormal chromosomes were evaluated for 80 patients whose diagnosis and prenatal counselling were performed in our centre. Twenty-two anomalies were diagnosed by chorionic villus sampling (CVS) and 58 by amniocentesis. The severity of the chromosome anomaly and associated ultrasound findings in the first vs. second trimester were correlated with patients' decisions. No difference was found in the likelihood of parental decisions to interrupt or continue a pregnancy between CVS and amniocentesis for either the 'severe' or the 'questionable' group of chromosome anomalies. Ninety-three per cent of patients with severe prognosis and 27 per cent with questionable prognosis opted for pregnancy termination (p less than 0.0001). The association of ultrasound anomalies and termination was highly significant (p less than 0.001). The severity of the chromosome anomaly, and, to a lesser extent, the visualization of anomalies on ultrasound were the major determinants of parental decisions to terminate the pregnancy. The diagnosis of an anomaly in the first trimester was no more likely ito lead to a termination of pregnancy than in the second trimester. PMID- 2267226 TI - Congenital hereditary hypothyroidism--prenatal diagnosis and treatment. AB - Intrauterine diagnosis of congenital hypothyroidism was established on the basis of TSH concentration in amniotic fluid in the 22nd week of gestation for the offspring of a couple both known to have an iodide organification defect. Prenatal treatment consisted of intramniotic injections of 500 mcg Na-1 thyroxine, which was administered from the first amniocentesis until one week before delivery. Following delivery, the diagnosis was confirmed by the elevated level of TSH, 60.5 uU/ml, and a gradual decrease of fT4 to 0.8 ng/ml. Regular substitution therapy was commenced on the third day of life. The normal shape and location of the thyroid gland was demonstrated by Technetium scintiscan. At 18 months the infant revealed no significant deviation from normalcy in growth or mental capacity. This experience indicates that testing of amniotic fluid for TSH in the 22nd week of gestation can be diagnostic for congenital primary hypothyroidism. Furthermore, it is suggested that the treatment approach described is warranted in all cases in which there is a high risk of congenital primary hypothyroidism. PMID- 2267227 TI - Ultrasonographic diagnosis of a fetal abdominal mass: a case of a mesenchymal liver hamartoma and a review of the literature. AB - A case of a prenatally recognized hepatic mesenchymal hamartoma is presented and the literature reviewed. These tumors are benign and usually present in early infancy with symptoms that are related to the mass effect on adjacent organs. Radiologic methods used in the past to image this tumor include angiography and ultrasound. However, there is no specific radiologic finding, and, therefore, the diagnosis is usually made during surgery. Once the tumor is removed, the prognosis is generally good. With the increasing use of high resolution ultrasound in prenatal diagnosis, this rare tumor should be considered in the differential diagnosis of any multicystic mass found in the fetal abdomen. The recognition of a mass should then alert the physician to the need for early neonatal intervention. PMID- 2267228 TI - Central nervous system damage and other anomalies in surviving fetus following second trimester antenatal death of co-twin. Report of four cases and literature review. AB - Four cases of multiple gestation with second trimester death of one fetus and subsequent damage to a survivor are reported. Monochorionic placentation was documented in three of the cases. Central nervous system lesions occurred in all cases, and bowel injury was noted in two of the damaged fetuses. Although rare maternal clotting problems have been reported in similar situations, none was noted in any of these four cases. Prior reports have indicated that losses in the first half of gestation were of no consequence to the surviving fetuses. These four cases contradict this suggestion, and indicate that close sonographic observation of the survivors is important in any multiple gestation where on fetus has died. PMID- 2267229 TI - Sensitivity of chromosomal mosaicism detection by different tissue culture methods. AB - In the field of prenatal cytogenetic diagnosis, two tissue culture methodologies are currently in use: the flask method, which examines mixed populations of cells, and the in situ method, which examines distinct colonies of cells. These two methods provide inherently different levels of sensitivity which can be made comparable by adjusting the number of cells examined depending on the methodology used and the number of colonies formed per ml of specimen. Assuming that there are 2 colonies per ml of amniotic fluid in a 20 ml specimen, in order to detect 10, 20, and 30 per cent mosaicism with 95 per cent confidence, 29, 14, and 9 colonies should be examined respectively by the in situ method. Similarly, 50, 17, and 10 cells must be analysed by the flask method. PMID- 2267230 TI - Prenatal diagnosis of haemophilia A by the polymerase chain reaction using the intragenic hind III polymorphism. AB - A method is described which uses the Hind III polymorphism in intron 19 of the factor VIII gene for genomic family analysis and prenatal diagnosis by the polymerase chain reaction. The primers derived from the exon 19 and 20 sequences allow amplification of the whole intron 19 resulting in a 730 bp fragment. Hind III restriction of this fragment provides fragments of 250 bp or 160 bp and 90 bp respectively, specific for the intragenic Hind III polymorphism. The constant 480 bp fragment can be used as an internal control to circumvent misdiagnosis due to incomplete or failure of restriction. Using this method a prenatal diagnosis of haemophilia A in the first trimester of pregnancy is demonstrated. PMID- 2267231 TI - Prenatal diagnosis of a partial 8p trisomy. AB - The index patient is a female fetus in which prenatal diagnosis of 8p trisomy was established after amniocentesis at 16 weeks of gestation. This fetus was the unbalanced product of a maternal translocation of 5q/8p (karyotype: 46,XX,t(5;8)(q35;p11). Internal malformations include an anomalous lobature of the right lung, a little and high atrio-ventricular communication, and an anomaly in the number and shape of the aortic semilunar valves. The possible relationship between the phenotype and the chromosomal abnormality is briefly discussed. PMID- 2267232 TI - Intrauterine growth retardation associated with chromosomal aneuploidy confined to the placenta. Three observations: triple trisomy 6,21,22; trisomy 16; and trisomy 18. AB - Cytogenetic analysis in three pregnancies revealed chromosomal mosaicism confined to chorionic villi. They were ascertained in the third trimester by intrauterine growth retardation (IUGR) in otherwise normal fetuses. In case of triple trisomy 6,21,22 and trisomy 16, it was obvious that these findings were most likely restricted to the placenta. These trisomies act as early lethal factors when they occur in the embryo itself. With trisomy 18, however, the interpretation of the cytogenetic finding remains ambiguous. The question arises as to whether an abnormal karyotype may be the cause of placenta insufficiency or is just coincidentally associated. PMID- 2267233 TI - Fetal chimerism or fetal mosaicism? PMID- 2267234 TI - Letter of retraction. PMID- 2267235 TI - Trisomy 12 mosaicism in phenotypically normal fetuses following prenatal detection. AB - We report three cases of amniocentesis in which mosaicism for trisomy 12 was detected in two or more independent cultures. The parents elected to terminate the pregnancy in all three cases. Follow-up studies in two of the cases confirmed the mosaicism in fetal tissues (in subcutaneous tissue in one case; in fetal lung in the other), but not in blood. No fetal anomalies were evident by ultrasound or at autopsy. These results along with other reported cases demonstrate the difficulty in counselling for mosaic trisomy 12. PMID- 2267236 TI - Transvaginal chorionic villus sampling. AB - Chorionic villus sampling (CVS) with either transcervical catheters or transabdominal needles is a widely-accepted method for prenatal diagnosis. However, there exists a small subset of patients in whom sampling is difficult or impossible with either route because of individual anatomic variations. A new method of chorionic villus biopsy has been developed to circumvent these problems, utilizing transvaginal chorionic needle aspiration guided by an intravaginal ultrasound probe. This technique was performed successfully in 15 patients in whom villi could not be obtained by either of the conventional methods. This method now makes CVS possible in essentially all women regardless of their uterine anatomy or placental placement; it may also prove useful for very early chorionic sampling. PMID- 2267237 TI - Antenatal ultrasonic diagnosis of dyssegmental dysplasia: a case report. AB - Sonographic prenatal diagnosis and management of a pregnancy complicated by dyssegmental dysplasia of the Silverman-Handmaker type are presented. This is a documented case of this type of short-limbed dwarfism presenting in a family of Hispanic-American ancestry. PMID- 2267238 TI - Chorionic villus sampling for prenatal diagnosis in Wales using DNA probes--5 years' experience. AB - Chorionic villi were sampled from 125 women who requested prenatal diagnosis, either for genetic disorder or because of advanced maternal age. Of these, 105 samples were obtained by the transcervical route and 20 were obtained by the transabdominal approach. The sampling success rate was 97 per cent (122/125). The mean maternal age of the patients was 31 years (range 17-44) and the mean gestational age at which the chorionic villus sampling was performed was 10 weeks (range 7-13 weeks). Seventy-four of these diagnoses involved the use of DNA markers. The minimal size of the sample used for DNA diagnosis was 5 mg. Maternal contamination was detected in two samples. A diagnosis was provided on all but two samples. The fetal loss rate was high initially but fell to 1.9 per cent in 1988. PMID- 2267239 TI - Discordant findings in chorionic villus direct preparation and long term culture- mosaicism in the fetus. AB - Prenatal cytogenetic study of chorionic villi showed a discrepancy between a normal female karyotype 46,XX in the direct preparation after short-term incubation, and a 45,X karyotype in the long-term culture. The subsequent amniocentesis revealed a normal karyotype in three cultures and a 45,X/46,XX mosaicism in one culture. Cytogenetic analysis of chorionic villi after termination of the pregnancy showed a normal karyotype in the direct preparation and a 45,X/46,XX mosaicism in the long-term culture. Fetal lymphocytes showed normal karyotypes, whereas fibroblast cultures revealed a 45,X/46,XX mosaicism. PMID- 2267240 TI - Cystic fibrosis prenatal diagnosis: confirmation of an equivocal microvillar enzyme result by direct analysis of the common gene mutation. AB - A child was tentatively diagnosed as having cystic fibrosis, based on neonatal presentation with severe gastrointestinal complications; the diagnosis was not confirmed biochemically and no tissues were available for DNA analysis. The mother presented in her subsequent pregnancy, and microvillar enzyme analysis of cell-free amniotic fluid at both 18 and 20 weeks gestation gave equivocal results. The pregnancy was terminated voluntarily because of a trend towards abnormal enzyme assay results on the second amniocentesis. Retrospectively, fetal tissues were found to be homozygous for the most common mutation of the cystic fibrosis gene (delta F508), which confirmed the prenatal assessment and suggested that the first infant of the couple was probably also affected by the disease. PMID- 2267241 TI - Congenital generalized cystic lymphangiomatosis diagnosed by prenatal ultrasound. AB - We describe a previously unknown congenital abnormality of the lymphatic system, characterized by multiple cystic lesions of the lower extremities and thorax. Diagnosis was made by ultrasound in the second trimester. The ultrasound findings, pathology results, and differential diagnosis are presented. PMID- 2267242 TI - Assessment of postoperative pain in critically ill infants. AB - Factors influencing the nursing diagnosis of pain in postoperative infants were investigated in a qualitative study. Crying was identified as the major indicator of pain. Work experience was identified as the major influence on analgesic administration by registered nurses (RNs). Needs for nursing education were identified. PMID- 2267243 TI - Management of heart failure in cardiac surgical patients: amrinone and other pharmacologic agents. AB - The pharmacologic treatment of heart failure and low cardiac output syndrome in the cardiac surgical patient continues to be a challenge in the nursing management of these patients. While the catecholamines have been of proven inotropic benefit over the years, their inherit risks of increased myocardial oxygen consumption, tachyphylaxis and poor tolerance in many patients have lead to the search for other medications to augment cardiac performance. Amrinone, the only drug available for use in the U.S. from the class of phosphodiesterase inhibitors, acts as both an inotrope and vasodilator to increase cardiac output without an increase in myocardial oxygen consumption. This paper reviews pharmacological management of heart failure in the cardiac surgical patient and nursing considerations specific to amrinone and combination inotropic therapy management. PMID- 2267245 TI - The cholesterol education program for nurses. PMID- 2267244 TI - Powerlessness and personal control model applied to the myocardial infarction patient. AB - The MI patient can experience powerlessness through loss of personal control. The feeling of powerlessness can limit the patient's ability to understand the diagnosis of MI, care or decisions necessary to restore health. The MI patient can react by experiencing a sense of physiological, cognitive, environmental and decisional loss of control. Regardless of the specific component of the powerless model, the coronary care nurse diagnoses powerlessness according to defining characteristics. Nursing interventions are organized to facilitate physiological, cognitive, environmental and decisional powerfulness. Research is needed to clarify the MI patient's perception of control or lack of control within each component of the presented model, and to evaluate the effectiveness of nursing interventions created to foster personal control or uncontrol. Research will enable the nurse to scientifically determine strategies and outcomes that correlate with the patient's need for control in the illness situation. PMID- 2267246 TI - Patient-nurse contracts in critical care: a controlled trial. AB - An experimental trial was conducted to measure the effects of a patient-nurse contract on patients' emotional state during hospitalization in the Coronary Care Unit (CCU). The contractual agreement focused on areas of environmental restrictions and nursing care in the CCU that might decrease patients' sense of control. Forty-one patients with documented coronary heart disease, never previously hospitalized, were randomly assigned to either a control or an experimental group upon admission to the CCU. The control group was oriented to the routines of the unit by one of the nursing staff, while the experimental group made individualized contracts with a nurse regarding family visitation, schedules for daily hygiene, patient teaching, activity and the room environment. A significant difference existed between the two groups over time for the three dependent measures of anxiety, depression and hostility (p less than .001). Twenty-four hours after completing baseline measures, the control group was significantly more anxious (p less than .01) and hostile (p less than .05) than the experimental group. At 48 hours, the experimental group reported significantly lower anxiety (p less than .01), depression (less than .05), and hostility (p less than .05) compared to the control group. These findings suggest that a strategy designed to enhance cardiac patients' sense of personal control may facilitate emotional adaptation to hospitalization. PMID- 2267247 TI - Adrenal modulation of the enhanced fat intake subsequent to fasting. AB - Elevations in corticosterone have been linked with the enhanced fat appetite of genetically obese Zucker rats. The present study set out to describe the effects of elevations in corticosterone in adult male Sprague-Dawley rats. Previous studies have shown that food deprivation leads to a time-dependent increase in basal corticosterone concentrations. It was predicted that rats would select a high fat diet during initial refeeding subsequent to a 24-hour fast and more severe food deprivation (48 hours) would promote greater fat consumption. Dependence upon adrenal hormones for this enhanced fat intake was examined with adrenalectomized animals. It was hypothesized that adrenalectomy would prevent the increase in fat intake seen in intact animals. Two experiments were performed. In the first, rats were given access to three separate macronutrient sources and allowed to self-select a diet for 7 days. They were then divided into groups and deprived of food for 0, 24, or 48 hours. At the end of the restriction period each rat was tail bled and macronutrient access was restored. Intakes were measured and blood samples taken at 1, 3, 6, 12, and 24 hours following restored access. During the first hour of refeeding, food-deprived animals ate significantly more fat than nondeprived animals. The enhanced fat intake was positively correlated with the elevations in corticosterone observed at the start of the refeeding period (r = .72). In the second experiment, rats were allowed to self-select a diet for 9 days. On Day 10 the rats received either bilateral adrenalectomies or sham operations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267248 TI - Control of water intake in thermally dehydrated rats. AB - Male rats were thermally dehydrated by exposure without water to an environmental temperature of 40 degrees C for 0-4 hr or to environmental temperatures of 25-40 degrees C for 4 hr. Water intake was then measured for 2 hr or a blood sample was taken to determine the effect of heat exposure on body water status. Evaporative water loss and water intake increased with increased duration and severity of heat exposure. Heat exposure significantly increased plasma osmolality and plasma sodium concentration and significantly decreased plasma potassium concentration. Hematocrit and plasma protein concentration increased slightly but not significantly with heat exposure. The increases in water intake in association with increases in evaporative water loss, plasma osmolality and plasma sodium concentration with no significant increases in hematocrit or plasma protein concentration indicates that the thirst induced by thermal dehydration is primarily osmotic in nature. Water intake equal to about 50% of the evaporative plus urinary water loss reduced plasma osmolality and sodium concentration to control levels, removing the stimulus to drink before the water loss was replaced. PMID- 2267249 TI - Photoperiodic responsiveness in house mice. AB - House mice (Mus musculus) and laboratory strains of rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because their reproductive systems are unaffected by day length (photoperiod). In rats, however, at least three experimental manipulations, perinatal testosterone injection, chronic peripubertal testosterone exposure, or peripubertal olfactory bulbectomy, have revealed latent reproductive photoperiodism. The effectiveness of these experimental treatments may be unique to albino rats. Alternatively, these experimental manipulations may unmask the ability to discriminate short from long days in several "nonphotoperiodic" species and, thus, reveal clues to common physiological mechanisms underlying reproductive responsiveness to photoperiod. In the present study, male house mice were 1) subjected to olfactory bulbectomy or a sham operation at 23 days of age, 2) injected with testosterone or the oil vehicle at 3 days of age, or 3) implanted subcutaneously with an empty Silastic capsule or one filled with testosterone at 22 days of age. All mice were subsequently housed either in LD 16:8 or LD 4:20 photoperiods. The physiological mechanisms necessary to discriminate long from short day lengths are extant in house mice. Testicular mass was significantly reduced in short-day bulbectomized males when assessed 6 weeks postoperatively, but not when measured 10 weeks after surgery. Similarly, mice injected with testosterone when 3 days old and reared in short days had smaller testes as compared to testosterone-treated males housed in long days. Mice implanted with testosterone capsules regressed their reproductive systems regardless of photoperiod. Other reproductive organ weights followed the same general pattern of results as for testicular mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267250 TI - Hormone-dependent aggression in male rats is proportional to serum testosterone concentration but sexual behavior is not. AB - Male hooded rats were castrated and implanted with Silastic capsules (1.57 mm i.d.; 3.18 mm o.d.) having a testosterone-filled space 0, 7, 22, 60, or 90 mm long. All animals were returned to their original group cages for a three-week period to allow hormone concentrations and behavioral tendencies to stabilize. Each male was then housed with an intact female in a large cage. Aggression by the male toward an unfamiliar male was tested at weekly intervals for three weeks. Sexual behavior with an estrogen/progesterone-primed ovariectomized female was tested on each of the subsequent two weeks. Serum testosterone was measured during the following week. The frequency of aggression was correlated with serum testosterone concentration up to the normal level and did not increase with higher serum testosterone concentrations. In contrast, sexual behavior was virtually absent in animals with no testosterone replacement and normal in all other groups. These results demonstrate a clear dissociation in the dependence of hormone-dependent aggression and sexual behavior on serum testosterone concentration. In a male cohabiting with a female, sexual experience activates hormone-dependent aggression toward an unfamiliar male but the level of aggression that develops depends on the serum testosterone concentration in the resident male. PMID- 2267251 TI - Intestinal infusion of a liquid diet alters CCK and NPY concentrations in specific brain areas of rats. AB - Cholecystokinin (CCK) and neuropeptide Y (NPY) have been implicated in the control of food intake in a number of species. This study was carried out to determine 1) whether nutrient-related stimulation of the upper small intestine could activate central CCK and NPY neuronal systems, resulting in changes in concentration of these peptides in specific brain areas, and 2) the influence of the circadian cycle on nutrient-related effects. Four groups of rats received treatments of either 1.0 ml saline (S) or Ensure liquid diet (E) infused into the duodenum either during the dark (D) or light (L) phase of the circadian cycle. CCK and NPY concentrations in extracts of specific brain areas were measured by RIAs. CCK concentration in the supraoptic n. (SON) was higher in D than in L, regardless of infusion treatment, and in the dorsal parabrachial n. area (DPN), CCK concentration was higher in E than S infused rats, regardless of circadian phase. CCK concentration in the dorsal motor vagal n. area (DMV) was higher in E, but only during L. NPY concentration was higher in DPN and paraventricular n. areas (PVN) and lower in the suprachiasmatic n. area (SC) after E, regardless of circadian phase. The changes in concentration of CCK and NPY in specific brain areas in response to food in the upper intestine suggest that nutrient-related signals from the intestine can activate specific CNS CCK and NPY-containing neural pathways. PMID- 2267252 TI - Photoperiodic regulation of the time of birth in rats: involvement of circadian endogenous mechanisms. AB - A resonance experiment was undertaken to demonstrate that photoperiod regulates birth time by endogenous circadian mechanisms. Pregnant rats were maintained on a standard light-dark (LD) cycle (14L-10D; lights on from 0600 to 2000 hr) or on fixed LD cycles with periods of 12, 24, 36 and 48 hours after day 8 of gestation. In these groups, the light phase (2 hr) started between 0600 and 0800 hr or between 1800 and 2000 hr illuminating exclusively (for periods of 24 and 48 hr) or alternatively (for periods of 12 and 36 hr) the hours corresponding to morning (M) or evening (E) of the standard light regimen. At the end of gestation, the general activity was manifested mainly at moments corresponding to the night of the standard regimen in most groups; it was delayed in the two groups lit up exclusively at E hours. In groups receiving light exclusively at M hours, birth times were delayed compared to the deliveries in groups receiving light at E hours only. An intermediate distribution of birth times was observed when M and E hours were stimulated every 12 hr but not every 36 hr. The apparent stability of the diurnal rhythm of activity and the difference in birth time distributions due to the period of light phase indicate that the regulation of birth time by photoperiod is due to a circadian mechanism in rats. This mechanism implicates at least two endogenous systems which are apparently antagonists with regard to birth. PMID- 2267253 TI - Olfactory bulb removal: effects on sexual behavior and partner-preference in male rats. AB - Control and bilaterally bulbectomized male rats were tested in an arena where the male could choose to spend time with (and mate with) a sexually receptive female, a nonreceptive female, or be in a neutral compartment. Control males mated with, and showed a strong preference for, sexually receptive females. Bulbectomy virtually eliminated mating. In addition, bulbectomized males showed no preference for a receptive female over a nonreceptive female, and spent their time equally between the receptive female, the nonreceptive female, and the neutral compartment. Effects of bulbectomy on preference and copulation could be consequences of a severely impaired ability to smell--the perception of odors may be essential for sexual arousal, or the absence of preference and copulation after bulbectomy might reflect a deficit in the male's ability to make odor dependent classification of conspecifics as appropriate sexual partners. Or the behavioral effects of bulbectomy might reflect a disruption of tonic input to the forebrain that has little or nothing to do with the sensory impairment that follows bulb removal. But whatever the reason, in partner-preference tests bulbectomized males show a striking indifference to the sexual status of females, and it seems likely that the failure to mate is causally linked to this effect of surgery. PMID- 2267255 TI - Variations of core-temperature rhythms in unrestrained sheep. AB - Variations of core-temperature rhythms occurring during a "normal" day (24-hour period without extraordinary challenges for organism) were studied in 5 male sheep. To record the influence of the metabolic processes in different organic systems, core temperatures were measured at various locations at the same time. To minimise any influences due to measurement or behavior (e.g., effects of isolation), a telemetric system was used for registration and animals were kept without restraint in their habitual herd. Particularly biphasic circadian rhythms were found, and feeding schedule as zeitgeber is discussed. Beyond that, independent from point of measurement short-time rhythms with wavelengths of 140 and 90 min were found. Therefore, an origin in the central nervous system can be supposed. Rhythms with wavelengths of 3 hours, 75 min and 1 hour were not stable throughout a whole 24-hour period and did not occur at all measurement points in the same intensity. A comparison of anatomical placements of the various measurement points leads to the realization of distinct organic functions as sources for these rhythms. PMID- 2267254 TI - The role of sucrose-sensitive neurons in ingestion of sweet stimuli by hamsters. AB - The relationship between sweet preference and activity in sucrose-sensitive chorda tympani nerve fibers was investigated in hamsters (Mesocricetus auratus). Without exception, hamsters increased consumption of aqueous solutions of nonsweet 0.1 M NaCl, 0.001 M quinine-HCl, 0.01 M citric acid, 0.001 M dithiothreitol, 0.01 M pyridine, 0.01 M 2-phenylethanol, 0.005 M i-amyl acetate, 0.01 M vanillin, half-saturated 1-menthol and 0.033 mM capsaicin if they were made sweet by adding 0.5 M sucrose. Since sucrose activates chorda tympani S fibers, activity in these nerve fibers may be sufficient for increased preference. To determine if S-fiber activity is necessary for preference, equally preferred sweet stimuli were presented to the tongue while recording responses of single chorda tympani fibers. S fibers were clearly activated by 0.03 M sucrose, 0.001 M Na saccharin, 0.01 M D-phenylalanine, 0.1 M glycine, 0.005 M dulcin and 0.03 M Na 2-mercaptoethanesulfonate but not by 0.01 M Ca cyclamate and 0.003 M Na 3-nitrobenzenesulfonate. Ca cyclamate weakly activated H fibers and Na 3 nitrobenzenesulfonate weakly activated N fibers. Thus, S-fiber chorda tympani activity may be sufficient but not necessary for sweet preference, which may be influenced by activity in fibers of other taste nerves. PMID- 2267256 TI - Right-sided population bias in male rats: role of stress. AB - Recent studies have shown that rats develop a pronounced right-sided population bias when tested repeatedly over several days in a shock-escape T-maze paradigm. In the present study we sought to determine if this bias was the result of learning or of the repeated exposure to a stressor (footshock). Rats were tested in the T-maze for 5 trials on each of 6 consecutive days. One group of rats (HS C) was allowed a free left or right choice on each trial whereas another group of rats (HS-A) was forced to alternate left and right turns on each trial for the first 5 days of testing and then allowed a free choice on Day 6. The population and individual laterality of the HS-A group did not differ from that of the HS-C group, indicating that learning does not account for the biases. A third group of rats (LS-C) was tested using a lower shock level; this decrease in stressor intensity delayed the development of a right-sided population bias without affecting the development of individual laterality. These results indicate that repeated exposure to a stressor, rather than learning, is primarily responsible for the marked right-sided population bias observed in the T-maze. PMID- 2267257 TI - Nocturnal hemodynamic patterns in dogs. AB - Several species which have a single daily wake-sleep cycle show a progressive fall in cardiac output and rise in total peripheral resistance during sleep, a cardiovascular response which may reflect a progressive decrease in plasma volume. The present study showed that no such progressive overnight changes in cardiac output or total peripheral resistance occur in the dog, a carnivore which tends to be awake and to drink intermittently during the night. Progressive overnight bradycardia (-12.7 +/- 3.1%) and compensatory increase in stroke volume (14.8 +/- 6.0%) were observed in this species, however. These findings are consistent with the view that differences between primates and carnivores in overnight hemodynamic function are related to species differences in sleep and ingestive behavior. PMID- 2267258 TI - SBR: a computer program to record and analyse sexual behavior in rodents. AB - SBR (Sexual Behavior Recorder) is a program designed to record and analyse data from research on the sexual behavior of rats and other animals with similar patterns of sexual behavior. SBR allows the user to record the characteristic events of both the male and female's sexual behavior: mounts, intromissions, ejaculations and lordosis. It also allows the user to record two other types of events, and analyse them in terms of frequency and duration, using two user defined keys. The program allows the correction of any event erroneously recorded. SBR can simultaneously control observations made by one or two observers, and on one or two experiment boxes. In the case that two observers record from the same experiment box, the program calculates a set of measures of reliability between the observers. At the end of each observation, SBR conducts a descriptive analysis of the recorded events, including the parameters normally used in scientific literature on the subject, and writes this analysis to disk files. As well as the default calculation parameters, it is possible to calculate any other, or to use the program as a record of general purpose events using the file which contains all the recorded events in sequential order and the exact time at which they were recorded. SBR was written using the compiler Turbobasic 1.1 from Borland International Inc. (1987). PMID- 2267259 TI - [Art therapy in the psychiatric clinic. A historical analysis of the development of art studios]. AB - The present study examines the building up of art classes in psychiatric hospitals in the thirties and forties of this century. Until 1950 the worldwide total of 34 art classes had come into being. The growing psychiatric interest in drawings of patients in the 19th century is related to changes in psychiatric theory moving from "moral treatment" to descriptive psychiatry at the turn of the century. All in all the installation of 11 artistic workshops for patients can be traced before the 1st world war. They were part of work therapy in german private clinics as a means to put patients of a higher social standing to a regular activity instead of field and garden work, which was medically indicated but socially unacceptable. During the course of development of a diagnostic interest since 1870 the drawings were all along considered to be the immediate expression of the patients inner world. Such a view had become possible, after in modern art the conceptions about the meaning of art had changed. Paradigmatically this connection can be shown in the work of Prinzhorn. First therapeutic attempts were then started by different psychoanalysts especially in the treatment of children. These formed an important basis for the establishment of art classes in psychiatric hospitals later on. Painting was now considered as a means to approach the hidden unconscious. The study continues to explain in which way the therapeutic applications of art therapy depended on the convergence of view points in esthetic and therapeutic theory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267260 TI - [Diagnosis and treatment of borderline disorders within the scope of inpatient psychiatric care]. AB - Borderline-patients compose a group of severe problem-patients on psychiatric inpatient units. Among other topics this concerns the difficult differential diagnosis, attitudes of demandingness and entitlement, feelings of depressive despair, acting out and impulsive behavior. Using a process oriented diagnostical approach which includes the behavior of the patient on the unit and the analysis of the therapeutic interaction, the borderline disorder is differentiated from the psychoses on the one side and the neuroses on the other. The specific treatment problems of borderline-patients are dealt with under the headings of regression, splitting, projective identification and acting out. The counter transference problems of treatment teams are taken under special consideration. The last part of the article deals with treatment goals and therapeutic strategies in the psychiatric inpatient treatment of borderline patients and discusses possible modalities of adjunctive treatment. PMID- 2267261 TI - [Psychiatric disorders in immigrants. I. History, symptoms and diagnostic classification]. AB - 155 people who had left East-Germany and sought psychiatric help within six weeks after their arrival in West Berlin, were examined. History, living situation and psychopathological symptoms were studied. The disorders were diagnosed according to ICD-9 and DSM-III-R. 85% of the patients reported that they had already suffered from similar complaints in East Germany. 50% stated they have had symptoms before they had made the decision to leave. On average, that decision had been taken 22 months before the actual leaving. Most often patients complained about sleep disturbance, nervousness, and headaches. According to ICD 9, 55% of the disorders were classified as reactive and 39% as neurotic or personality disorders. The most frequent diagnoses according to DSM-III-R were adjustment disorders (41%), major depression (21%), anxiety disorders (16%), and dysthymia (14%). Regardless of diagnosis most patients were found to have symptoms of anxiety and depression associated with vegetative complaints. There were no clear relationships between psychopathological symptoms and data of history or present living situation. PMID- 2267263 TI - Clinical subtypes of unipolar depression: Part II. Quantitative and qualitative clinical differences between the vital and nonvital depression groups. AB - This study examines whether the differences in the cluster-analytically generated classes--nonvital versus vital depression--are dimensional (quantitative) rather than categorical (qualitative). To this end, we used various pattern-recognition methods based on principal component analysis (PCA), e.g., display methods (PC plotting), eigenanalysis, and SIMCA (statistical isolinear multiple components analyses). We found several arguments supporting the dimensional hypothesis that the nonvital and vital classes constitute relevant stages (continuous categories) in the continuum of illness-severity. Nevertheless, we found some arguments supporting the categorical hypothesis that the cluster-analytically generated classes are qualitatively different with reference to the similarity of the vital symptoms. Our findings suggest that a nosological or categorical classification is possible from the moment that one component (i.e., the vital component) is quantitatively prominent to the extent that it has become qualitative. As the overall severity of illness increases, vital symptoms emerge which, grouped together, shape a new symptom profile (i.e., vital depression). Thus, our results favor the hypothesis that there are simultaneous quantitative (dimensional: overall severity of illness) and qualitative (categorical: vital symptoms) differences between the nonvital and vital depression groups. PMID- 2267262 TI - Clinical subtypes of unipolar depression: Part I. A validation of the vital and nonvital clusters. AB - Cluster analyses were carried out on a sample of 100 depressed females. The study was based on the 14 items relevant to depressive phenomenology of the Structured Clinical Interview for DSM-III-R (SCID). Our findings support the existence of two classes, i.e., a vital (melancholic) vs. a nonvital cluster. The vital cluster is characterized by the following symptoms: a distinct quality of depressed mood, nonreactivity, early morning awakening, anorexia-weight loss, and cognitive and psychomotor disturbances. Patients belonging to the vital cluster exhibit disorders in the hypothalamic-pituitary-adrenal and thyroid axes and a markedly decreased availability of L-tryptophan to the brain. The vital depressives score significantly higher on the Hamilton Rating Scale for Depression as compared to those suffering from nonvital depression. The cluster analytically derived class of vital depression and the DSM-III subtype of melancholia tend to be quite similar. Our findings support the isolation and the descriptive validity of a vital (melancholic) depressive syndrome. PMID- 2267264 TI - Subtyping familial schizophrenia: reliability, concordance, and stability. AB - This report examines the reliability, concordance, and long-term stability of the subtypes of schizophrenia defined by four major diagnostic systems (DSM-III, DSM III-R, ICD-10, and Tsuang-Winokur criteria) and rated both for the first hospitalization and for a best estimate diagnosis reflecting lifetime evolution of symptomatology. Schizophrenics studied belonged to two samples of multiply affected families, namely a sample selected in France and a sample of non metropolitan French identified in the island of La Reunion. ICD-10 and DSM-III-R show opposite stringency regarding subtyping of schizophrenia, with DSM-III-R having a narrow and ICD-10 a broader definition of specific subtypes. Long-term stability of each subtype was fairly good, stability being the highest for hebephrenics and only intermediate for paranoid and undifferentiated subtypes. Comparison of two different cultural and geographical regions reveals an overall similarity of subtype frequencies in familial schizophrenia. The implications of the results for the choice of diagnostic procedures in family studies of schizophrenia are discussed. PMID- 2267265 TI - Smooth pursuit eye tracking dysfunction and negative symptoms in schizophrenia. AB - This study examined the hypothesis that negative symptoms are associated with abnormalities of smooth pursuit in schizophrenic patients. The pursuit eye movements of 25 subjects with schizophrenia and 25 matched normal control subjects were recorded using an infrared eye tracking system and quantified using the log of signal-to-noise ratio (1n S/N). The severity of negative symptoms within the schizophrenic group was rated using the Scale for the Assessment of Negative Symptoms. Previous findings of pursuit abnormalities among schizophrenic patients as a group were replicated. There was, however, no significant association between the eye tracking dysfunction and the severity of negative symptoms. PMID- 2267268 TI - The psychoanalytic process. PMID- 2267267 TI - Studying the psychoanalytic process: an introduction. PMID- 2267266 TI - The Yale-Brown Obsessive-Compulsive Scale: a reliability and validity study. AB - Twenty-eight nondepressed patients with DSM-III obsessive-compulsive disorder completed both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Leyton Obsessional Inventory (LOI) once a week for a total of three times change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global scores, the Y-BOCS was found to be more reliable than the LOI. Correlations were also obtained for the baseline period between the Y-BOCS and Leyton scores. At the end of a 14-week trial of clomipramine, the Y-BOCS and the LOI were again administered along with a Physician and Patient Global Rating of change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global Ratings. This last finding suggests that the Y-BOCS is a better measure of clinical change than is the LOI. PMID- 2267269 TI - The psychoanalytic process: motives and obstacles in the search for clarification. AB - One motive for regarding psychoanalysis as a "process," and for attempting to define its exact nature, is to enable analysts to clarify their criteria for distinguishing authentic psychoanalysis from other therapies that resemble it or are derived from it. In the present climate of theoretical pluralism, any list of defining qualities that could win wide acceptance would of necessity be cast in terms of such general quality as to limit its utility as a precise template. Another motive for holding on to the "process" concept arises from the unpredictable nature of analytic progress in even the most satisfactory cases. PMID- 2267270 TI - The psychoanalytic process and its components. AB - Certain problems in defining the psychoanalytic process emerged during the five years in which a COPE study group was attempting to clarify the concept. There was agreement about the bed-rock criteria to be included in a definition: e.g., transference, resistance, a dynamic unconscious, intrapsychic conflict, defense, infantile sexuality, insight which causes change, and change which brings insight. The disagreements centered on the locus of the psychoanalytic process, the best way to conceptualize change, and the methodological problem of validating whether specific interventions cause specific claimed effects. Confusion about how to account for the interactional aspect of the psychoanalytic situation in a manner consistent with a one-person psychology emerged as an important source of the difficulty in arriving at a satisfactory definition of the psychoanalytic process. PMID- 2267271 TI - Psychoanalytic process. AB - Differing concepts of psychoanalytic process and views of its "locale" are related to how essential the interactivity of the analyst is judged to be. Scientific scrutiny of clinical psychoanalysis requires that the interactive nature of the process be recognized. In this endeavor the concept of "process model" is helpful, as is the view of psychoanalysis as a form of treatment in which therapeutic process and therapeutic agent are distinguished. PMID- 2267272 TI - Mutative interpretation and close process monitoring in a study of psychoanalytic process. AB - When James Strachey defined the mutative interpretation, he did not have defense interpretation in mind, but a few years later Anna Freud opened the door to new ways of making small-scale non-transference and transference interpretations that alter superego functions. Using her model and a special mode of listening, the authors suggest an updated technique of intervention with resultant superego change, which qualifies for consideration as a later version of the mutative interpretation. PMID- 2267273 TI - Further observations on the psychoanalytic process. AB - The psychoanalytic process remains a fascinating and valuable concept, albeit an incompletely understood and controversial one. The author reviews the ideas in his 1984 essay and looks back on some of the critiques and proposals that followed that paper. He suggests that the concept of the psychoanalytic process is viable and useful despite its shortcomings. Consideration is given to the goals of psychoanalytic treatment as they relate to the "process" and how the "process" may be helpful in determining whether or not a patient is "in" analysis. PMID- 2267274 TI - The psychoanalytic process: the developmental and the integrative. AB - Psychoanalysis is a treatment that focuses on intrapsychic events and activates integrative tendencies to promote-insights. Almost from the time it originated, however, it was also promoted as a therapy informed by the interpersonal, inducing change through experiences generated within the psychoanalytic situation. In recent years the interpersonal or object relations approach has come to be categorized as "developmental," a term that fosters no end of ambiguities. The resulting confusion compromises the study of the actual developmental process on the one hand and the structure-enhancing features of transactions on the other. This encumbers research on the psychoanalytic process. The author distinguishes the intrapsychic from the interpersonal, the integrative from the developmental, and the two very different realms of psychological activities currently advanced as "developmental." PMID- 2267275 TI - The psychoanalytic process. AB - Analysts differ in how they conceptualize the psychoanalytic process, according to their understanding of the psychoanalytic theory of mental functioning in general and the nature of pathogenesis in particular. Emphasizing that psychoanalysis is a psychology of mental conflict, the authors see the psychoanalytic process in terms of the dynamic interplay between the manifestations of the patient's unconscious and the analyst's interventions. What analysts communicate to analysands serves to destabilize the equilibrium of forces within the mind, leading to the analysands' growing understanding of the nature of their conflicts and how they deal with them. Psychoanalytic process, accordingly, cannot be distinguished or separated from psychoanalytic technique. PMID- 2267276 TI - Conceptualizations of the psychoanalytic process. AB - A demonstrable psychoanalytic process involves elaborate and sustained intrapsychic experiences and phenomena for both analysand and analyst. It also includes a complex and at times subtle interpersonal relationship in which each participant is actively sensitive and responsive to verbal and nonverbal input from the other. These interpersonal experiences stimulate further intrapsychic responses which in turn may have further interpersonal effects. Within the framework of the psychoanalytic situation, these combined intrapsychic and interpersonal responses lead first to facilitative and ultimately to definitive changes in the patient's psychological organization and function. A method for demonstrating a psychoanalytic process is described. PMID- 2267277 TI - Psychoanalytic process and transference resistance, with notes on the need for re analysis. AB - In the course of conducting second analyses, the analyst has a uniquely advantageous position from which to study the psychoanalytic process. His or her observations of the unfolding of the second analysis can be compared with the analysand's description of the earlier experience. Investigation of the differences throws light on subtle aspects of transference resistances--how they have been manifested and how they have determined the outcome of the analytic process. The author focuses on some characterologic derivatives of latent transference resistances and discusses a way in which they may be drawn into workable aspects of the process they would otherwise impede. PMID- 2267278 TI - Managing strain in a classical analysis: re-establishing the therapeutic relationship or interpreting unconscious wishes. AB - The therapeutic relationship frequently comes under a strain during the course of an analysis. At these times, the analysand perceives and reacts to the analyst as if the analyst were a critical or seductive archaic object. When this occurs, the analyst has the choice of interpreting the unconscious source of the analysand's non-therapeutic reactions or of interacting with the analysand in a manner which re-establishes and potentially strengthens the therapeutic relationship. Interpretations during the early phases of an analysis are unlikely to mitigate the strain until the therapeutic relationship has become stronger and until considerable reality testing has promoted a context which allows the analysand to understand and to tolerate her or his unconscious wishes. PMID- 2267279 TI - Renovascular disease and renal complications of angiotensin-converting enzyme inhibitor therapy. AB - Renal complications of angiotensin-converting enzyme (ACE) inhibitor therapy are widely recognized, but few authors have documented the incidence or spectrum of these conditions. In a retrospective study of 530 consecutive patients presenting to our unit as acute uraemic emergencies over a six-year period, 85 (16 per cent) had renovascular disease that was considered to be responsible for their loss of renal function. Twenty-one (4 per cent) patients had uraemia which could be clearly attributable to ACE inhibitor treatment; 18 of these cases were shown to have significant renovascular pathology. Following withdrawal of the ACE inhibitor the renal failure reversed in the majority of patients. We also examined 400 consecutive hypertensive patients referred over a similar period and, although vascular imaging was performed only when it was considered to be clinically indicated, 58 (14.5 per cent) of these patients were shown to have renovascular pathology. A further five patients with stable chronic renal disease were seen to have a deterioration in their glomerular filtration rate coincident with commencement of ACE inhibitor therapy; this reversed when the agents were withdrawn. These observations indicate that significant renovascular disease may be more common than has been hitherto recognized and that injudicious use of ACE inhibitors may result in serious complications. Methods which may minimize such iatrogenic disease are suggested. PMID- 2267281 TI - Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature. AB - During a nine-year period, 14 cases of mycobacterial infection (tuberculosis) developed in 403 renal transplant recipients at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, an incidence of 3.5 per cent. The annual incidence of tuberculosis was about 50 times higher than that in the general population. Infection was disseminated in nine (64.3 per cent), pulmonary in four (28.6 per cent), and genitourinary in 1 (7.1 per cent). In one patient tuberculosis was transmitted by the donor's kidney. The clinical manifestations were often ill-defined and not different from that in the normal host. Cultures from all patients grew Mycobacterium tuberculosis; concomitant infection with other organisms was present in five patients (35.7 per cent). Two of 18 patients (group 1) with positive pretransplant tuberculin skin test developed tuberculosis after transplantation (11 per cent), and neither received isoniazid prophylaxis; three of 70 patients (group 2) with negative skin tests developed tuberculosis after transplantation (4.3 per cent). The difference between the two groups was not statistically significant. Review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases. Tuberculosis was disseminated in 38.7 per cent, pulmonary in 40.2 per cent, cutaneous in 12 per cent, and miscellaneous in 9.4 per cent. Atypical mycobacteria were responsible for 29 per cent of disseminated infections, 8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis. Invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis (p less than 0.0001). The mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent (p less than 0.005). These findings (1) confirm the higher incidence of tuberculosis in renal transplant recipients, compared to the general population; (2) suggest that pretransplant skin testing probably has little value in identifying patients at risk; (3) show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis; (4) confirm that the donor kidney may be an important source of infection; and (5) indicate that concomitant infection with other organisms is common. PMID- 2267280 TI - Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. AB - The clinical and laboratory features of 29 patients who had one of three anti aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome. PMID- 2267282 TI - Dialysis arthropathy: a clinical, biochemical, radiological and histological study of 36 patients. AB - Out of a population of 97 haemodialysis patients, 36 patients with dialysis arthropathy were identified. Dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years. It commonly affected the shoulders, hips, hands, knees and wrists, worsening with time and extending to other joints. Fifty-eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis. Half of the patients also suffered from carpal tunnel syndrome, which recurred and was associated with a long-lasting disability. The most common radiological abnormality was periarticular bone cysts, followed by articular erosions and a destructive spondyloarthropathy, but clinical symptoms were more common than radiological signs. Patients with dialysis arthropathy had a higher C-reactive protein level than patients without arthropathy (18.6 mg/l versus 11.4 mg/l), indicative of an inflammatory process. Some of the clinical manifestations of the disease correlated with levels of C-reactive protein and ferritin. Serum ferritin levels correlated strongly with the units of blood transfused in the past five years (RS = 0.83), and the logarithm of ferritin level correlated weakly with C-reactive protein (r = 0.32). Haemarthroses were documented in 19 per cent of patients. Mean serum beta 2-microglobulin was elevated in the patients with (57.3 mg/l) and without arthropathy (50.7 mg/l), and there was no difference in the parathormone or aluminium levels between these groups. Articular tissue was obtained in 25 patients; beta 2-microglobulin amyloid was present in 24. Larger deposits were present in the capsular tissue, and these appeared to replace collagen bundles in eight cases. Amyloid deposits replaced the lining layer in six cases. It is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue. Mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases. These findings suggest that amyloid derived from beta 2-microglobulin has a primary role in the pathogenesis of dialysis arthropathy, but there was also evidence of inflammatory processes. It is suggested that iron overload or haemarthroses might contribute to the inflammation, but other factors, such as dialysis-related bioincompatibility reactions, may also have a role. PMID- 2267283 TI - Angiotensin-converting enzyme inhibition and renovascular disease. PMID- 2267284 TI - Nurse terminated for election to public office. PMID- 2267285 TI - Nurse's attorney denied access to her personnel file. Case in point: Harmon v. Mercy Hospital (460 N.W. 2d 404--ND (1990)). PMID- 2267286 TI - Board disciplines nurse for failure to report subordinate. Case in point: Ethridge v. Arizona State Bd. of Nursing (796 P. 2d 899--AZ (1990)). PMID- 2267287 TI - Mediatophore: a nerve terminal membrane protein supporting the final step of the acetylcholine release process. PMID- 2267288 TI - Cell surface ATP (P2y) purinoceptors trigger and modulate multiple calcium fluxes in skeletal muscle cells. PMID- 2267289 TI - Immunogenetic mechanisms in myasthenia gravis. PMID- 2267291 TI - Clinical pharmacokinetics of acetylcholinesterase inhibitors. PMID- 2267290 TI - Newly recognized congenital myasthenic syndromes: I. Congenital paucity of synaptic vesicles and reduced quantal release. II. High-conductance fast-channel syndrome. III. Abnormal acetylcholine receptor (AChR) interaction with acetylcholine. IV. AChR deficiency and short channel-open time. PMID- 2267292 TI - Synaptic adaptation in diseases of the neuromuscular junction. PMID- 2267293 TI - Current treatment of myasthenia gravis. PMID- 2267294 TI - Current therapy of the Lambert-Eaton myasthenic syndrome. PMID- 2267295 TI - Structural and functional aspects of acetylcholine peptide coexistence in the autonomic nervous system. AB - The present article is an attempt to briefly review acetylcholine and peptide coexistence in the ANS. For more detailed information the reader is referred to the book by Furness and Costa (1987) and books edited by Elfvin (1983) and Bjorklund et al. (1988). Acetylcholine is the "classical" transmitter substance between preganglionic and post-ganglionic neurons in both the sympathetic and parasympathetic nervous system but also between postganglionic parasympathetic neurons and effector cells. ENK and NT were early on shown to be present in preganglionic sympathetic neurons whereas SP and SOM have more recently been associated with these cells. Physiological experiments have shown that ENK may presynaptically inhibit cholinergic transmission in sympathetic ganglia. The cholinergic postganglionic parasympathetic neurons contain VIP/PHI. These peptides may be responsible for the atropine-resistant vasodilation seen after stimulation of parasympathetic nerves. In salivary glands VIP has been shown to potentiate the salivatory volume response to ACh. A number of postganglionic sympathetic neurons innervating exocrine sweat glands in the skin are also cholinergic. In addition to VIP/PHI, these neurons contain CGRP and probably also SP. The functional significance of acetylcholine coexisting with four vasodilatory peptides in this cell population is at present unclear. In the enteric ganglia the coexistence situation is very complex. Thus, in the myenteric plexus cholinergic SP-containing excitatory motor neurons seem to be present. In the myenteric plexus other cholinergic neurons may contain at least six different neuronal peptides. These latter neurons seem to be part of the peripheral intestino-intestinal reflex arc which is involved in regulation of gastrointestinal motility and mucosal functions. In the submucous plexus three populations of cholinergic neurons are present, one of which has secretomotor properties and contains CGRP, CCK, GAL, NPY and SOM. In vivo and in vitro studies have shown that developing sympathetic neurons can "change" the "classical" transmitter they-use and alter their neuropeptide expression. If dissociated sympathetic neurons are grown in cultures without any non-neuronal elements they differentiate into a noradrenergic phenotype. However, if the cultures also contain non-neuronal cells, both noradrenergic and cholinergic properties will develop. These changes may also by induced by a conditioned medium, containing a diffusible factor secreted from the non-neuronal cells. In conclusion, the present article underlines the complexity of the chemical neuroanatomy of the ANS and emphasizes the abundance of the peptides in both noradrenergic and cholinergic neurons. Although these peptides can be shown to exert a number of interesting effects in various experimental paradigms, much work is needed to define their exact role in nervous system function. PMID- 2267296 TI - Pharmacological muscarinic receptor subtypes. PMID- 2267297 TI - Basic and clinical aspects of cholinergic agents in bladder dysfunction. PMID- 2267298 TI - Multiple pathways for signal transduction through the muscarinic cholinergic receptor. PMID- 2267299 TI - Future prospects in muscarinic cholinergic pharmacology. Outstanding problems and promises. PMID- 2267300 TI - Human brain cholinergic pathways. PMID- 2267301 TI - Cholinergic receptors in the rat and human brain: microscopic visualization. PMID- 2267302 TI - Principal aspects of the regulation of acetylcholine release in the brain. PMID- 2267303 TI - AF64A-induced cholinergic hypofunction. PMID- 2267304 TI - Choline acetyltransferase: a molecular genetic approach. PMID- 2267305 TI - New approaches to clinical and postmortem investigations of cholinergic mechanisms. PMID- 2267306 TI - The cholinergic system in Alzheimer disease. PMID- 2267307 TI - Positron emission tomography and cholinergic mechanisms: an overview. PMID- 2267308 TI - Spinal cholinergic mechanisms. PMID- 2267309 TI - An animal model of motor neuron disease in guinea pigs. PMID- 2267310 TI - Antimuscarinic drugs in the treatment of movement disorders. PMID- 2267311 TI - Cholinergic agents in clinical anaesthesiology. PMID- 2267312 TI - Acetylcholine and acetylcholine receptor subtypes in REM sleep generation. PMID- 2267313 TI - Future prospects of research on central cholinergic mechanisms. PMID- 2267314 TI - Function of nicotinic synapses. PMID- 2267315 TI - Physiological cholinergic functions in the CNS. PMID- 2267316 TI - The synthesis of acetylcholine: twenty years of progress. PMID- 2267317 TI - Achievements in cholinergic research, 1969-1989: drug development. PMID- 2267318 TI - Expression and in vivo amplification of the human acetylcholinesterase and butyrylcholinesterase genes. PMID- 2267319 TI - The basal lamina and stability of the mammalian neuromuscular junction. PMID- 2267320 TI - Functional aspects of quantal and non-quantal release of acetylcholine at the neuromuscular junction. PMID- 2267321 TI - Carbohydrate histochemistry of epithelial glycoproteins. PMID- 2267322 TI - [DNA sequencing with a DNA sequencer using fluorescence labelling]. PMID- 2267323 TI - [DNA sequencing with modified T7 DNA polymerase]. PMID- 2267324 TI - [Methods of DNA sequencing with Taq DNA polymerase]. PMID- 2267325 TI - [Rapid cDNA sequencing method using the polymerase chain reaction]. PMID- 2267326 TI - [Pulsed field gel electrophoresis]. PMID- 2267327 TI - [Whole genome physical mapping--strategies for making ordered clone banks]. PMID- 2267328 TI - [Cloning with mini-F plasmid of exogenous large DNA segments]. PMID- 2267329 TI - [Molecular cloning of cDNAs encode sequence-specific DNA-binding proteins by a southwestern method]. PMID- 2267330 TI - [Regulation of gene expression using artificial introns]. PMID- 2267331 TI - [In situ hybridization]. PMID- 2267332 TI - [Microcell-mediated chromosome transfer--identification of chromosomes carrying a tumor-suppressor function]. PMID- 2267333 TI - [Molecular cloning of the unknown genes from mutant cells]. PMID- 2267334 TI - [Development and application of vaccinia virus vector]. PMID- 2267335 TI - [Identification and functional analysis of novel proteins deduced from the cDNA sequences: protein kinase C related proteins]. PMID- 2267336 TI - [Manipulating mouse genome: a new strategy for studying mammalian molecular genetics]. PMID- 2267337 TI - [Introduction of foreign genes into plants using a Ti plasmid vector]. PMID- 2267338 TI - [Chloroplast proteins: biosynthetic pathway and gene manipulation]. PMID- 2267339 TI - [Regulation of plant gene expression by light]. PMID- 2267340 TI - [Gene expression in Streptomyces]. PMID- 2267341 TI - [Secretion of heterologous proteins by the yeast Saccharomyces cerevisiae]. PMID- 2267342 TI - [Functional analysis of lysozyme by conversion of amino acid residues]. PMID- 2267343 TI - [Production of recombinant human erythropoietin using recombinant DNA technology]. PMID- 2267344 TI - [Protein engineering of human pancreatic secretory trypsin inhibitor (PSTI)]. PMID- 2267345 TI - [Construction of a yeast strain that produces non-infective hepatitis B virion like particles]. PMID- 2267346 TI - [Application of gene recombination for cell breeding]. PMID- 2267347 TI - [Guidelines for the application of rDNA organisms--mainly application in the open environment]. PMID- 2267348 TI - [Risk assessment of environmental release of recombinant organisms--plants and microorganism]. PMID- 2267349 TI - [Chronic ulcerative stomatitis (CUS): a new disease entity with specific immunological marker (SES-ANA)]. AB - A review of recently described cases with oral chronic erosive or ulcerative lesions associated with stratified epithelium specific antinuclear antibodies (SES-ANA) is presented. The lesions are refractory to local and systemic corticosteroids but may be responsive to hydroxychloroquine. PMID- 2267350 TI - [Fibronectin in the skin of patients with allergic dermatitis]. AB - In the skin of healthy subjects linear deposits were found of fibronectin at the dermoepidermal junction and in the walls of blood vessels, and reticular deposits in the papillary and reticular layers of the skin. In the epidermis of 12 out of 51 patients with allergic contact dermatitis fibronectin deposits were found in relation to Langerhans cells and keratinocytes. This was not observed in the epidermis in healthy subjects. The authors suggest that fibronectin on the surface of Langerhans cells and keratinocytes may play a role in antigen presentation. PMID- 2267351 TI - [Ultrastructural image of the Langerhans cells in the skin of patients with allergic contact dermatitis]. AB - The alterations in the ultrastructural feature of Langerhans cells in patients with allergic contact eczema were characterized by significant increase in number of Birbeck granules accompanied by the increase in volume of smooth- and rough surfaced endoplasmic reticulum. These changes may be regarded as a morphological expression of the increase of the synthetic and secretory activity of the Langerhans cells. In the epidermis the Langerhans cells associated with immediately adjacent precursor cells (the so called indeterminate cells), lymphoid cells and keratinocytes form the morphologically visible and probably functional units. PMID- 2267353 TI - [Studies of the mechanism of disorders of the natural killer cell activity in patients with systemic scleroderma]. AB - The NK activity of peripheral blood mononuclear cells (PBMC) was evaluated in 90 patients with various subsets of systemic scleroderma (SSc). The NK activity, as performed with K-562 as target cell, was found to be significantly lowered in patients with diffuse scleroderma, but did not differ from the healthy control in patients with acrosclerosis. The lowest values in the NK activity assay were obtained in patients with most extensive skin involvement and severe internal organ changes. The NK activity of healthy donors' PBMC was significantly decreased by addition of SSc patients PBMC (50:1) to the cytotoxicity assay, but was not influenced by the patients sera. PMID- 2267352 TI - [Studies of the role of cellular immunity and angiogenetic changes in the pathogenesis of circumscribed scleroderma]. AB - The studies were performed in 48 patients with morphea and included evaluation of 1) antinuclear antibodies 2) lymphocyte induced angiogenesis 3) natural killer (NK) cell activity and 4) T cell subpopulations in peripheral blood. The presence of antinuclear antibodies was found in 44.4% (8/18) patients with scleroderma linearis and in 21% (4/19) patients with morphea disseminata. Lymphocyte induced angiogenesis was increased in 41.5% (17/41) morphea patients, mainly in cases with pronounced vascular changes. The E rosette forming test showed a decreased percentage of active rosette forming cells (ARFC) and total rosette forming cells (TRFC) in peripheral blood and the NK cell activity was lowered in patients with morphea. These results obtained in patients with morphea show some similarities and differences in comparison to cellular immunity disturbances in patients with systemic scleroderma. PMID- 2267354 TI - [Incidence of contact allergy in patients with eczema nummulare]. AB - In patients with eczema nummulare patch tests with a panel of 18 allergens were done with positive result in 9 (18%) cases. In 6 cases multivalent allergy was found. Most frequently positive tests were obtained with potassium dichromate. The tests showed participation of contact allergy in the development of changes in a part of patients with eczema nummulare. PMID- 2267355 TI - [Lysozyme in atopic dermatitis]. AB - The aim of the present study was to determine the levels of lysozyme in serum and saliva in 10 patients with atopic dermatitis (AD). A significantly decreased lysozyme levels in saliva compared to controls (p less than 0.01) were showed, whereas no differences were found in lysozyme activity in serum of patients and controls. The reduced levels in saliva can hardly be explained. The decreased levels of lysozyme in external fluids may be one explanation for the well-known predisposition for AD patients to an increased susceptibility to many cutaneous infections. PMID- 2267356 TI - [Local use of leukotriene inhibitor--NDGA in psoriasis]. AB - NDGA is known as an inhibitor of leukotrienes and may exert some effect on psoriatic lesion formation. The aim of the study was to test the influence of this drug on appearance of psoriatic plaques. 7 day application of 0.015% NDGA on psoriatic lesions under occlusion in 23 patients, gave some flattening of lesions as compared to controls. However, after finishing of application all the changes reappeared in previous form. We have never observed permanent beneficial effect in any patient. PMID- 2267357 TI - [Immunotypes of Chlamydia trachomatis and the clinical picture of non-gonorrheal urethritis in men and cervicitis in women]. AB - 102 Chlamydia trachomatis isolates obtained from pregnant women and 42 isolates from man-consorts of women with chlamydial infection of cervix were immunotyped using a microimmunofluorescence (micro IF) with monoclonal antibodies kit (Washington Research Foundation, Seattle, USA). In both groups of patients the most common serovars were: E (37.3%) and D (24.6%) belonging to B-complex. Additional serovars noted were: F (11.3%), J (11.3%), I' (4.5%), I (3.5%, K (3.5%), G (2.8%) and H. Ba (both 0.2%). N. gonorrhoeae and/or T. vaginalis infections were more frequent from patients with B-complex Ch. trachomatis serovars (28/75 that is 37%) than C-complex Ch. trachomatis serovars (3/25 that is 12%). PMID- 2267358 TI - [Clinical picture of early syphilis in patients with HIV infection in the light of literature data]. AB - A literature survey is presented concerning the clinical pattern of early syphilis in subjects infected with HIV. The course of syphilis infection in HIV positive subjects differs often from the usual one, the clinical picture may be that of the so called malignant syphilis with early development of syphilitic lesions in the central nervous system and involvement of the visual system; Serological reactions differ also, they may give negative results or may appear with delay, sometimes high titres of these reactions are found. PMID- 2267359 TI - [12-year trends in cardiovascular disease mortality]. AB - The coefficients and trends of mortality in years 1976-1987, based on data of Central Statistical Office, has been estimated in population of men and women aged 25 to 64 years, inhabitants of the Warsaw city region or the county region of Tarnobrzeg province . The trend of decrease of general mortality due to diseases of circulatory system has been statistically significant one similarly as that of mortality due to other heart diseases or ischaemic heart disease in men (group aged 25-34 or 35-44 years) in the Tarnobrzeg province . The analogously significant trend of mortality due to diseases of circulatory system or ischemic heart diseases in men aged 35-44 years has been stated in the Warsaw inhabitants. In the group of women an increase of general mortality has been noted in the youngest age group in Warsaw. In Warsaw and the Tarnobrzeg province in 1987 deaths due to diseases of circulatory system represented 33.2% and 39.9%, respectively, of total death pool among subjects aged 25 to 64 years. The respective percentages in the group of women were 29.1% and 39.4%. PMID- 2267360 TI - [Myocardial infarction incidence and mortality among urban and rural populations during the 3-year period]. AB - In years 1984-1986 3639 men and 1885 women were registered with suspected myocardial infarction from right-side Warsaw, simultaneously 2371 men and 917 women with the same suspected disease were registered from the Tarnobrzeg province population. The myocardial infarction diagnosis was confirmed in 54% of men and 43% of women from the Warsaw population as well as in 77% of men and 66% of women from Tarnobrzeg province population. In Warsaw the standardized incidence due to myocardial infarction increased during years of study from 466 to 588/100,000 among men and from 178 to 206/100,000 among women. The analogous increase among the Tarnobrzeg province population was 302 to 559/100,000 among men and 64 to 195 among women. Fatality during 28 days from the onset of the disease did not show any relationship with year of study and corresponded yearly among men to 45% and among women to 37% in Warsaw and to 42% among men and 33% among women in the Tarnobrzeg province . High fatality was noted during first 24 hours of hospitalization (Warsaw: 36% among men and 26% among women, Tarnobrzeg: 39% among men and 32% among women). The highest fatality was noted in the youngest of analysed groups. PMID- 2267361 TI - [Stroke incidence and mortality among urban and rural populations during the 3 year period]. AB - In years 1984-1986 582 men and 338 women have been registered with clinical diagnosis of cerebral stroke. The respective numbers in the Tarnobrzeg province were 340 and 263. Preliminary diagnosis of cerebral stroke was confirmed according to criteria of registration in 82% of men or women from Warsaw and in 81% of men and 84% of women in the Tarnobrzeg province . Standardized incidence due to cerebral stroke was significantly higher in every of analysed years in the Warsaw population both among men and women in compare with that in the Tarnobrzeg province . In both population studied the incidence was significantly higher among men than among women. Standardized fatality during 28 days from the start of sickness was higher in the Tarnobrzeg province population than in the Warsaw population so far as both men and women are concerned. In both populations among men and women the most frequently diagnosis was acute disease of cerebral vessels. PMID- 2267362 TI - [Characteristics of the main risk factors of coronary disease among the population of Warsaw and rural agricultural population of the Tarnobrzeg province]. AB - Basing on results of first screening of the Pol-MONICA Project in 1984 in two centres that is the Tarnobrzeg province and two districts of Polish capital Warsaw (Praga South and Praga North) the level of 11 main coronary disease risk factors was compared in 2469 men and 2729 women. The following 5 risk factors were statistically significant for both men and women: the Durnin index of body fat content, the total cholesterol concentration in the plasma, triglyceride level, numbers of daily meals. The mean level of two factors that is the HDL cholesterol concentration and the HDL-cholesterol/total cholesterol ratio was lower in the Warsaw sample what speaks in favor of concept that the ischemic heart disease threat is greater in that population. Among men the Warsaw population exhibited moreover the significantly higher value of diastolic blood pressure as well as of Quetelet body mass index; age and numbers of cigarettes smoked daily has also been higher in that population. In women from the Tarnobrzeg province ++ the diastolic blood pressure was higher than that in the Warsaw population. The two populations studied showed also highly significant differences so far as the complex of all 11 features is concerned what enabled the qualification of 72.3% of men, and 68.4% of women as belonging to the big city population or to the agricultural-industrial population using the discriminant Fisher function. PMID- 2267363 TI - [Effect of inter-population differences in the levels of selected factors on the differences in arterial blood pressure]. AB - According to the Pol-MONICA program the random selected population samples were studied in inhabitants of Warsaw or the Tarnobrzeg province . After excluding from analysis the subjects treated with the hypotensive++ or hypolipemic drugs the differences between populations studies with regard to range of mean pressure value, except systolic pressure (RRs) in women, appeared significant ones. In populations studied the arterial blood pressure (CTK) was influenced by: age, sex, education, family history with regard to the circulatory system, the alcohol intake, smoking, heart action frequency the Quetelet coefficient value, triglyceride concentration and daily sodium intake. After analysis of inter population differences in values of above factors the mean RRs values in populations studied did not differed significantly whereas differences in mean values of diastolic pressure (RRr) were highly statistically significant. PMID- 2267364 TI - [Plasma lipid and lipoprotein levels among rural and urban populations in Poland in relation to risk factors of coronary disease]. AB - There are significant differences in plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and blood pressure, prevalence of cigarette smoking, obesity, education level and alcohol consumption found between the rural and industrial populations in Poland. It was found that the differences in plasma lipids and lipoproteins concentration are related to the differences in age, sex, education level, alcohol consumption, obesity, cigarette smoking and blood pressure. Increase of education level was related to increase in plasma concentration of total cholesterol. LDL-cholesterol and triglycerides but it was related to decrease of HDL-cholesterol. After the adjustment to all above factors the differences in total cholesterol and LDL-cholesterol between the studied populations appeared insignificant. The differences in HDL-cholesterol and triglycerides remained significant. PMID- 2267365 TI - [Comparison of parameters and factors affecting the differences in obesity among urban population of Warsaw and the rural agricultural-industrial population of the Tarnobrzeg province]. AB - Comparison of the parameters of obesity between two populations, urban from Warsaw and agricultural-industrial from Tarnobrzeg province revealed that skinfolds thickness, Quetelet index and body fat index, and per cent of overweight were statistically significantly higher in men from urban population. In the group of women these parameters were also statistically higher in Warsaw population with the exception of triceps skinfold and Quetelet index--differences of no statistical significance. There were also differences in the set of variables which correlate with the parameters of obesity between these two tested populations. PMID- 2267366 TI - [Regional conditions of the smoking habit-- the POL-MONICA 1984 studies]. AB - The POL-MONICA Project screened in 1984 1309 men and 1337 women aged 35 to 64 years, inhabitants of Warsaw (the Warsaw centre) and 1250 men and 1472 women aged 35 to 64 years, inhabitants of the Tarnobrzeg province (the Cracow centre). In both environments the percentage of smoking men was similar (about 57%). Women from big city environment smoked three times more frequently (33.1%) than in the agricultural areas (10.7%). The smoking intensity was higher in the agricultural areas both among men and women. It has been stated that smoking habit depends on such social or demographic patterns as age, sex, civil state, education, physical activity related to work. Smoking influenced significantly the level of such risk factors as systolic arterial blood pressure, the fat body content in both men and women, and the HDL-cholesterol in women from both environments. PMID- 2267368 TI - [The statistical reliability of a report versus the professional judgment of the radiologist]. PMID- 2267367 TI - [Hypertension--diagnosis, treatment and the effectiveness of the treatment of Polish population participating in the POL-MONICA program]. AB - According to the POL-MONICA program basing on screening studies of random population samples of two Warsaw districts and the Tarnobrzeg provinceip the detectability of arterial hypertension (AH), the AH treatment fact, the effectiveness+ of AH treatment and the populational control of AH has been evaluated. The AH control was better in Warsaw (men 55%, women 73%) than in the Tarnobrzeg province (men 44%, women 65%). In both populations the control was better among women than among men and increased with the age of subjects investigated. In both populations the treatment was introduced only in half of detected AH and increased also with the age of subjects studied. Only 20% men and 25% of women in Warsaw and 35% of men and 42% of women in the Tarnobrzeg province was effectively treated. The AH control in the Warsaw population was twice a lower than in the Tarnobrzeg province (Warsaw: men 5%, women 10%, Tarnobrzeg: men 7%, women 16%). Exceptionally bad control of HT has been stated in the youngest and the middle age men group in Warsaw (2.9%). The patterns studied with the use of MLF functions in both population studied have significant influence on the detectability and the AH treatment fact and remain without the influence of effectivity of treatment. PMID- 2267369 TI - [Magnetic resonance angiography of the intracranial vessels. Technique and anatomy]. AB - Fifty volunteers were studied by means of MR angiography of the intracranial vessels, with a 1.5 T Siemens Magnetom. The technical features of the most employed MR angiographic techniques were analyzed. The inflow technique was tested with refocused gradient-echo sequences for the FISP 3DFT flow and a dedicate coil. The study was aimed at evaluating the resolution power of each technique and at identifying the most useful rotations and angles for each chosen vessels. The acquisition volume of the gradient-echo sequence was positioned on the axial plane with sella turcica in the center. TR was set at 0.04 s, TE at 10 ms, and flip angle was 15 degrees. A 256 x 256 matrix was used, and an 80-mm acquisition volume, with 64 partitions. The chosen images were rotated on the axial and sagittal planes 0 degrees-180 degrees. The results showed that both rotation planes and their relative angles allow the visualization of all the vessels. To reduce post-processing time, with immediate availability of computer keyboard, a standardization is suggested with 0 degrees-180 degrees rotations on the axial plane, with 15 degrees interval and 0 degrees-45 degrees rotations on the sagittal plane, with 15 degrees interval. The main limitation of this method is its spatial resolution, which was 1.2 mm in rotations and acquisitions on the axial plane and 1 mm in acquisitions on the axial plane rotated on the sagittal plane. PMID- 2267370 TI - [Magnetic resonance angiography of the vessels of the neck. Study technique and normal anatomy]. AB - Magnetic Resonance Angiography (MRA) is a new diagnostic technique which allows vascular structures to be studied atraumatically and without any contrast medium. Its basic principles are reported in the present paper, together with the results of a preliminary study of normal neck anatomy. Twenty healthy volunteers and 10 patients with no cerebral vascular diseases underwent this MRA study. Internal and common carotid arteries were always well visualized, while external carotid was demonstrated in 87% of cases. Among intracranial vessels, the middle cerebral artery was clearly depicted in 63% of cases, while the anterior cerebral artery was visible in 18% of the study population only. PMID- 2267371 TI - [Magnetic resonance imaging of aortic and mitral valve insufficiency. Comparison with Doppler echocardiography and angiocardiography]. AB - Fourty-five subjects--10 normal volunteers and 35 patients with valvular insufficiency were examined with MRI and [20 of them with mitral (MI) and 15 with aortic (AI) insufficiency] were evaluated with MR imaging and with Doppler echocardiography (echo-Doppler); 22 of these patients were also studied with angiocardiography. The extent of regurgitation jet was classified as follows: minimal (1+), mild (2+), moderate (3+), and severe (4+), according to the max distance of regurgitant jet signal from valvular leaflets. In our series, MR imaging with FFE sequences always showed the regurgitant jet. High agreement was found between MR and echo-Doppler results (80% for MI, and 86% for AI). In 22 patients who underwent angiocardiography, we observed 73% agreement. Cine-MR imaging proved to be an accurate and sensitive technique to recognize and to evaluate severity of regurgitant valvular flow in patients with AI and MI. This technique may be useful in those patients in whom Doppler echocardiography is inadequate or impossible to perform. PMID- 2267372 TI - [Usefulness and limitations of neuroradiologic tests (CT, US, MRI) in periventricular leukomalacia]. AB - Sixteen young patients, with clinical and radiological signs of periventricular leukomalacia (PVL), were investigated with MR imaging. Twelve of them were investigated with US in the perinatal period. The extant 4 patients, older than the others, had a clinical history of PVL. US scans were capable of yielding precise information about the anatomical features of PVL in both the acute and the middle phases. The lesions appeared as hyperechoic areas which subsequently turned to anechoic cavities. MR imaging and CT scans did not present any particular advantage over US scans in the acute phase, but they did detect periventricular damage when the patient was 6-7 months old. MR imaging was superior to CT in detecting the delayed myelination of white matter. Inversion recovery sequences gave more anatomical details to distinguish normal from abnormal white matter. Spin-echo proton-density images detected periventricular gliosis, which appeared as persistent hyperintense areas. CT might be useful in the acute phase, after US detection of hyperechoic intraparenchymal areas, for it allowed purely ischemic lesions to be distinguished from hemorrhagic ones. PMID- 2267373 TI - [Magnetic resonance imaging of low intensity field in the follow-up of pneumonectomized patients]. AB - The authors investigated the real contribution of low-field MR imaging in the follow-up of pneumonectomized patients. Literature on the subject is surprisingly poor, even though MR diagnostic capabilities seem to be great in these patients. Because of the peculiar anatomical features of pneumonectomized patients, low field MR imaging yields high-quality images. The operated hemithorax, with the postpneumonectomy space full of fluid, in the absence of respiratory movements is free of movement artifacts. The latter are known to worsen image quality in thoracic MR imaging, especially without respiratory gating. In the study of mediastinum and operated hemithorax MR imaging provides the highest diagnostic contribution. In the mediastinum MR images demonstrate enlarged lymph nodes and tumor recurrences and is superior to CT especially when great vessels are involved. In the study of the operated hemithorax, MR imaging is preferable to CT to identify parietal lesions, because of its higher spatial resolution. Moreover, MR imaging allows tumor recurrences to be differentiated from normal muscular tissue and from fibrous tissue on the basis of their different signal intensities as observed on the various pulse sequences. PMID- 2267374 TI - [Reliability of computerized tomography in the definition of the "N" parameter in the preoperative evaluation of primary bronchopulmonary tumors]. AB - In order to evaluate the reliability of thoraco-mediastinal CT in the preoperative evaluation of primary lung cancer, regarding "N" (lymph nodes) parameter, we compared CT data with those obtained at histopathology of mediastinal lymph nodes. We re-examined 130 patients who had undergone lobectomy or pneumonectomy combined with mediastinal node dissection. CT criterion of neoplastic nodal involvement is morphological, based on size of the node as related to its location. CT is very sensitive in evaluating both normal and pathological nodes but not likewise specific; in fact, it does not allow differential diagnosis between neoplastic and phlogistic causes. This limitation must be kept in mind in the preoperative evaluation of the "N" parameter. Moreover, CT findings of mediastinal involvement on the opposite side (N3) must be confirmed with mediastinoscopy or CT-guided biopsy before ruling radical surgery out. PMID- 2267375 TI - [Computerized tomography in the staging of carcinoma of the oropharynx, the tongue and the mouth floor]. AB - Eighty-seven patients with carcinoma of oropharynx, tongue and floor of the mouth were examined by means of CT; (TNM criteria); tumor staging was reviewed and compared with that obtained by clinical examination, by endoscopy, at surgery and histology. CT proved to be a reliable technique to detect both the presence of neoplasms, with the exception of very superficial ones, and their deep spread to parapharyngeal space, to muscles of floor of the mouth and prevertebral pterygoid muscles. Lymph node metastases, especially to retropharyngeal nodes, were also clearly demonstrated on CT scans, which indicates this technique as the examination of choice in oropharyngeal and oral cavity tumor staging, for it yields valuable information which can integrate clinical findings. PMID- 2267376 TI - [Comparative arthrographic and echographic study of degenerative lesions of the rotator cuff of the shoulder]. AB - Sonography is a simple technique which is currently employed in the study of rotator cuff lesions in the shoulder. A comparative US and arthrographic study was carried out on 52 patients with a "painful shoulder", to evaluate US yield in this pathologic condition. Arthrography was positive for a rotator cuff lesion in 31/52 cases (25 full-thickness and 6 incomplete lesions) and demonstrated associated conditions (capsulitis, chondral lesions, lesions of the long head of biceps, capsulo-ligamentous hypotonia, effusions) in 11 case. Arthrographic findings were negative in 10 cases. US demonstrated a lesion in 25/31 of positive arthrographic cases, and it was negative in 3/6 incomplete lesions. In 7/11 patients US yielded additional information as to associated conditions. US false positives were 3/10, while in the extant 7/10 cases US was negative too. Thanks to its high sensitivity and specificity (80% and 70%, respectively, in our series), US appears as a valuable diagnostic complement to arthrography; the former may even replace the latter in those cases where conservative treatment is expected. PMID- 2267377 TI - [Contribution of echography to the study of the tendinous structures of the small joints]. AB - The authors describe the US patterns of normal small-joint tendons and of soft tissue masses, together with the inflammatory and traumatic changes in tendon echogenicity. The relationship of small-joint tendons to surrounding structures is also reported. Sixteen patients aged 1-60 years were examined. The indications for US examination were: pain, impaired motion, or evidence of a palpable mass. The normal contralateral region was always studied for comparison. US showed 13 pathologic conditions and 3 normal patterns. 6 patients underwent surgery, while the other 10 were treated by medical therapy. US diagnosis was confirmed in 15/16 cases (13/13 pathologic conditions and 2/3 normal patterns); surgery demonstrated a partial tendon rupture in the only false negative at US. Sonography proved thus useful also in the imaging of small-joint tendons. This technique, which demonstrates normal and pathologic tendon patterns, helps make a correct diagnosis and plan the appropriate treatment. PMID- 2267378 TI - [Ultrasonography in the study of synovial disorders and tendon lesions in rheumatoid arthritis]. AB - Conventional radiology is the main diagnostic tool for the visualization of osteoarticular lesions in rheumatoid arthritis. Articular effusions and popliteal cysts were examined with US. This paper is aimed at proving US capabilities in yielding important information about articular and peri-articular soft tissues in the early phases of rheumatoid arthritis. Over the last 30 months, the shoulder, wrist, hand, knee, and hip of 73 rheumatoid patients were studied by means of US and conventional and microfocal radiography. The patients were divided into 2 groups according to the time of onset of the disease. In group A, US demonstrated early synovial exudative inflammation, whereas conventional and microfocal radiography mainly demonstrated soft tissue swelling. In group B (where the first onset dated back to over 1 year), US demonstrated exudative and proliferative changes, together with recurrences. The authors believe US to be able to recognize the early changes of rheumatoid arthritis: as a matter of fact, US shows articular and periarticular soft tissues abnormalities and allows a differential diagnosis to be made between exudative and proliferative forms. PMID- 2267379 TI - [Significance of Harris' lines in fractures of the legs. Review of 53 cases]. AB - Metabolic deficiencies of various kinds, acute or chronic diseases, and especially bone fractures may cause the formation of transverse thickening lines- known as Harris' lines--in bone metaphysis. The authors have selected 53 cases of lower limbs fractures in young people from their clinical reports and studies. These reports included X-ray studies or other data allowing comparison of the injured segment at a significant time interval from trauma. The importance of Harris' lines, which appear in a high percentage of cases, is discussed also from a medical jurisprudence point of view, as these lines clearly indicate the time when the fracture occurred and the subsequent evolution of the repair process. PMID- 2267380 TI - [Trans-sphenoidal spread of rhinopharyngeal neoplasms. Correlations between computerized tomography and magnetic resonance]. AB - In 1957 Teoh observed, in an autopsic series of 31 patients with nasopharyngeal carcinoma, 3 cases of neoplastic spread through the marrow spaces of the base of the skull, without macroscopic bone alterations. In order to demonstrate in vivo this kind of neoplastic spread, CT and MR examinations of 35 patients with nasopharyngeal carcinoma were reviewed. In 3/26 cases the invasion of the marrow spaces of the clivus was demonstrated. In these cases CT showed only minimal alterations in spongiosa and cortices of the clivus, associated with intracranial soft-tissue tumoral components. MR imaging demonstrated, with great accuracy, the replacement of bone marrow in the clivus by neoplastic tissue of intermediate signal intensity on T1-weighted images. Tumor tissue was characterized by high signal intensity on T2-weighted images. The authors stress the greater utility of MR imaging in evaluating the permeative involvement of the base of the skull. PMID- 2267381 TI - [Preliminary experience of the study of the hand using digital radiology with photo-excitable phosphors and direct magnification. Comparison with the traditional high resolution technique]. AB - Photostimulable phosphor computed radiography (CR) is a new technique. The authors applied direct magnification CR to hand study (IP matrix: 1770 x 2370), and compared the results with conventional radiography ones (high MTF industrial type film, without screens, 5 x optic enlargement reading). In both cases, a mammographic unit was employed for acquiring the images. Thirty patients affected with renal osteodystrophy, psoriatic arthropathy or rheumatoid arthritis, and 20 normal subjects were examined. Digital images were processed by a particular sensitometry curve and spatial filtering with unlinear unsharp masking: we obtained good visualization of small lesions (subperiosteal resorption, cortical bone tunnelling, minute periosteal necrosis), not inferior to that obtained with conventional techniques. CR has further advantages, such as low economic and biological cost, wide exposure and recording range, image processing, easy archiving and networking. PMID- 2267382 TI - [Use of ultrasonography to estimate fetal weight in premature infants. Development of a new mathematical formula]. AB - In 73 pregnant patients at a gestational age under 36 weeks, who gave birth within 72 hours from the last US examination, mathematical equations were elaborated. The equations were aimed at predicting fetal weight by measuring the main US biometric parameters; the results were compared to the actual birth weight. A statistical analysis was performed using the "backward elimination" method. The linear equation that has provided with the best estimation of fetal weight is the following: fetal weight = 12.9875 BPD +29.5642 AD +28.8023 FL 3496.1265. According to this equation, about 95.22% of the variability of the unknown quantity (i.e. birth weight) can be ascribed to its correlation to the variables: biparietal diameter (BPD), abdominal diameter (AD) and femur length (FL). Estimated fetal weight by US, as calculated on the basis of biparietal diameter, abdominal diameter and femur length measurements, showed, in our study, a standard error of 143 g (9.02%) (R = 0.95). PMID- 2267383 TI - [Opaque enema and radiography of defecation in the pre- and postoperative morpho functional evaluation of rectal neoplasms]. AB - From November 1989 to April 1990, 16 patients with rectal cancer were examined preoperatively by means of double contrast barium enema and defecography. Double contrast barium enema was used to identify the cancer: based on the distance of cancer from anal rima, the patients were divided into 3 groups: 1) less than 6 cm; 2) 6-11 cm; 3) more than 11 cm. In all patients defecography was performed at the end of barium enema to evaluate rectal wall mobility. Thus, the morphological information yielded by barium enema could be integrated with the dynamic data from defecography. The evaluation was thus possible of both longitudinal and, indirectly, transverse tumor spread. All the patients underwent surgery and radiological findings were compared with surgical ones. In those patients in whom defecography had shown rigidity of the rectal walls, extraparietal tumor spread was observed during surgical resection. Seven patients underwent anterior resection, and were subsequently examined by the same combination of barium enema and defecography. The combined use of the two methods was useful to evaluate the anastomosis and to show possible dynamic changes after surgery. PMID- 2267384 TI - [Splenic echography in blunt abdominal trauma]. AB - Eighty emergency US exams of the spleen for blunt abdominal trauma were performed in 1988-1989 to evaluate US accuracy and reliability. A real-time scanner with convex probes (3.5 and 5 MHz) was employed. The results were confirmed at surgery and/or clinics and instrumental examinations. Nineteen patients were positive at US (1 false-positive); US patterns were: 16 focal lesions of the spleen--6 of them isolated, 7 associated with endoabdominal effusion, and 3 with increased splenic size and endoabdominal effusion--and 3 with isolated hemoperitoneum. Splenectomy was performed on 16/80 patients (20%): 13 of them were positive at US, while in 3 patients splenic lesions were not demonstrated. Five patients were followed with clinical and instrumental examinations to complete remission. Our results [85.7% sensitivity (18/21) and 71.4% specificity (15/21)] confirm US reliability in the evaluation of splenic lesions in blunt abdominal traumas. PMID- 2267385 TI - [Use of ultrasonography in the diagnosis of acute appendicitis]. AB - To date, the diagnosis of acute appendicitis (AA) has been made primarily on clinical grounds and imaging techniques have been considered less useful. This paper is aimed at evaluating US utility in the diagnosis of AA. US scans of the appendix, after Puylaert, were obtained in 30 healthy subjects (group A), in 49 patients with recurrent pain in the iliac fossa (group B), and in 28 patients with clinical signs highly suggestive of AA (group C). In none of the subjects in group A was the appendix seen. Neither was it demonstrated in the patients in group B, all of whom underwent surgery and never presented with suppurating, phlegmonous, gangrenous, perforating AA and/or abscess. In the patients in group C, 20 of whom had a positive histology for AA, US demonstrated 17 true positive, 8 true negatives and 3 false negatives. We consider as useful in the diagnosis of AA the following US signs: 1) the appendix cannot be demonstrated, in which case AA is to be excluded; 2) the appendix can be seen and is still, non-compressible and exhibits thickened walls; 3) the appendix contains fecaliths. The latter 2 findings are suggestive of AA. Thus, US of the appendix is useful (100% specificity in group B) in excluding AA when clinical diagnosis is questionable, but the method proves less reliable (85% sensitivity in group C) when clinical presentation is more definite. PMID- 2267386 TI - [Diagnostic imaging of pancreatic metastasis]. AB - The authors present their personal series of pancreatic metastases (8 cases) which were evaluated with different imaging modalities--i.e., sonography, computed tomography, and angiography. Possibilities and limitations of non invasive modalities are pointed out, and the usefulness of angiography is emphasized for the identification of small hypervascular lesions. The fairly rare diagnosis of these tumoral lesions is due to 3 causes: low incidence of pancreatic metastases; their frequently small size which justifies eventual false negatives; the frequent lack of symptoms calling for imaging modalities. Moreover, pancreatic metastases are usually diagnosed in an advanced stage. Thus, the therapeutic approach must be planned in every single case, in relation to the perspectives of survival and to the residual quality of life. PMID- 2267387 TI - The role of mammography in women under 30. AB - The authors report on a consecutive series of 305 women under age 30 undergoing mammography because of a solid palpable mass. The presence of diffuse parenchymal density impairing radiologic interpretation was observed in 71% of cases. Cancer was not demonstrated at mammography in 5 of 18 cases. Radiologic suspicion did not improve the cumulative sensitivity for cancer and did not influence clinical management in cancer cases. Mammographic contribution in reducing unnecessary biopsies of benign lesions was also poor and parallelled that of aspiration cytology. Mammography is not recommended in the differential diagnosis of palpable masses in women under 30 and should be limited to the preoperative assessment of cases with a strong suspicion of cancer. PMID- 2267388 TI - [Diagnostic imaging of pulmonary emphysema. From radiography to high-resolution computerized tomography]. PMID- 2267389 TI - [Radiologic study of colitis]. PMID- 2267390 TI - [Radiotherapy of rhinopharyngeal carcinoma: analysis of the caseload of Varese (1979-1986)]. AB - From December 1979 to December 1986, 100 patients affected with nasopharyngeal carcinoma, staged according to TNM (UICC-1978) criteria received exclusive radiation therapy at the Radiotherapy Department of the General Hospital of Varese. The median follow-up is 36 months (range: 1-114). Irradiation was delivered with 10 MV photons (58 patients) or 60Co (42 patients), with two opposed parallel lateral fields and progressive shrinkage, or rotation technique. Direct fields of electron beams (6-15 MeV) were employed as boosts on the residual nodes. Median total dose: 60 Gy to T, 46 Gy to N0, 62 Gy to N1-3. A conventional fractionation (2 Gy once a day, 5 times a week) was used in 43 patients, while an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week) was employed in 57 patients. Five-year overall survival (Kaplan Meier) of the 100 treated patients is 54.9%, while 5-year disease-free survival of the 71 patients in complete clinical remission at the end of radiation therapy is 54.7%. The nodal status represents the most important prognostic variable: 5 year overall survival (100 patients) is 77.7% for N0 patients and 40.8% for N1-3 patients, while 5-year disease-free survival for the 71 patients in clinical remission at the end of radiation therapy is 78.9% and 48.8% for N0 and N1-3 patients respectively. Our findings confirm the high rescue rate (approximately 50%) of irradiation failures by re-irradiation and/or salvage surgery. The analysis of loco-regional recurrences and persistent disease, after radiotherapy, strongly suggests the need for an improvement in loco-regional control rates, by means of a more accurate treatment planning (with CT and MR) and more attention to isoeffect parameters (CRE). The incidence of distant metastases (14%) and difficulties in loco-regional control of advanced disease seem to suggest the use of combined chemo-radiotherapy modalities only for selected groups of patients and exclusively in randomized studies. PMID- 2267391 TI - [Cerebral metabolism and permeability of the hemato-encephalic barrier in an experimental model for brain radiotherapy]. AB - Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2 deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans. PMID- 2267392 TI - [Radiotherapy plus a combination of cisplatin and 5-fluorouracil for locally advanced head and neck neoplasms. Study of feasibility and preliminary results]. AB - In March 1989 we started a feasibility study of combined radio-chemotherapy in patients with locally-advanced head and neck cancer. The first phase of treatment consisted of conventional radiotherapy (2 Gy/day, 5 days/week for a total dose of 70 Gy to primary tumor and +/- 50 Gy to nodes) and cisplatinum (20 mg/m2, i.v., for 4 days) +5FU (200 mg/m2, i.v., for 4 days) every 4th week, during radiant sessions. The second phase of treatment was started about one month after the end of simultaneous chemotherapy and radiotherapy: patients in complete remission received 1 more cycle of chemotherapy, as consolidation, while patients in partial remission received two more cycles of chemotherapy. Non-responding patients received no more chemotherapy. During the second phase the days of cisplatinum and 5FU were 5. Up to April 1990, 17 patients have been included in the study. They were stage III (64%) and IV (36%). The mean administered dose of radiotherapy was 66 Gy (range: 60-70 Gy) to primary tumor and 60 Gy (range: 40-70 Gy) to nodes. The total number of chemotherapy cycles administered during radiant sessions was 37, the mean number of cycles was 2 (range: 1-3), with 100% dose percentage. The interval between cycles was 3 weeks in 84% of patients. The relationship between number of cycles administered and planned cycle was 37/39 (feasibility: 95%). Acceptability was 100% (no patient refused the treatment). Feasibility of the second phase was 77% and acceptability 90% (1 patient refused the treatment). Toxicity was moderate during the first and the second phases. After the first phase 14/15 evaluable patients (92%) had major response (complete remission: 46%). After the second phase 10/10 evaluable patients had a complete remission. In conclusion, this combined treatment is very easy to administer, and very well accepted. Moreover, it yields a high number of objective responses. PMID- 2267393 TI - [Exclusive radiotherapy of stage Ib cervix carcinoma]. AB - From January 1st 1970 to December 31 1987, 178 consecutive cervical cancer Ib patients were treated at the Istituto del Radio, University of Brescia, by means of radiotherapy alone. In spite of the negative selection of the patients (advanced age, poor general conditions, associated pathologies) the results were good: 5-year cumulative survival was 86.5%, with a total failure rate of 13.5% (24 failures: 18 in the pelvis, 3 metastases and 3 both). The incidence of major complications (G2-G3-G4 of the Italian-French glossary) was 20% (36 patients): 19 G2, 15 G3 and 2 G4. The results in terms of survival and complications were related to the prognostic factors of the tumor (histology, grading, tumor size), of the patient (age, Karnofsky scale, associated pathologies, number of erythrocytes and hemoglobin rate) and treatment modalities (total dose, fractionation, combination of intracavitary brachytherapy and external beam). PMID- 2267394 TI - [Breast carcinoma. Technical problems of radiotherapy. Proposal of an algorithm as an alternative to the lack of scintigraphic visualization of the internal mammary lymph nodes]. AB - In early breast cancer, radiation therapy following conservative surgery needs a topographic evaluation of internal mammary lymph nodes. Three-dimensional lymphoscintigraphy (IML3D) is an useful method for this purpose. The average depth of the lymph nodes is closely correlated with the square root of the body weight/height ratio. We calculated the individual maximum depth of the lymph nodes from this function; the parameter was then verified with the experimental data from our series of cases (53 patients). Although the suggested algorithm needs to be verified on a larger number of patients, we believe the empirical maximum depth measurement to be useful when IML3D is unfeasible or the internal mammary lymph nodes are not demonstrated on scintigraphic scans. PMID- 2267395 TI - [Brachytherapy of carcinoma of the tip of the nose. A new technique]. PMID- 2267396 TI - [Estimate of organ doses in radiodiagnostic examinations]. PMID- 2267397 TI - [NIOBI-X filter: reduction of patient exposure and effect on image quality]. AB - Patient protection against ionizing radiation has become more and more important and the subject has been included in all the latest ICRP publications. Recently a 50 microns Niobium filter (NIOBI-X) has come out, which, installed on tungsten anode X-ray apparatuses, allows patient dose reduction by absorbing the radiation which does not contribute to the image. In order to verify the NIOBI-X actual effect on image quality and on patient dose reduction, image resolution, image contrast and patient exposure (air-Kerma) were measured using a bone-equivalent stepped wedge. The NIOBI-X, added to the total filtration of the X-ray apparatus, allows an air-Kerma reduction of about 50% from 60 to 130 kV. In the case of bone equivalent material exposure the filter causes a slight contrast loss and does not affect, or even improves, image resolution. Before choosing the NIOBI-X filter for all the X-ray apparatuses a cost-benefit analysis should of course be made by evaluating results and cost related to other kinds of filter. With particular regard to Aluminium filters, whose prices are far lower than Niobium ones, it has to be pointed out that: 1) in order to have the same air-Kerma reduction the Aluminium filter thickness must be quite heavy (2.8 mm) which causes practical problems of use; 2) the Aluminium filter causes image quality loss especially at lower kVs. PMID- 2267398 TI - [A case of relapsing tracheo-bronchial polychondritis]. PMID- 2267399 TI - [Fine needle biopsy guided by ultrasonography in a case of mesothelioma]. PMID- 2267400 TI - [Computerized tomography with surface reconstruction, in a case of posterior choanal atresia]. PMID- 2267401 TI - [A case of astragalocalcanean synostosis]. PMID- 2267402 TI - [A case of spontaneous and stabilized regression of lumbar disk herniation]. PMID- 2267403 TI - [A case of acinic cell carcinoma of the parotid gland treated with radiotherapy combined with hyperthermia and Doridamine]. PMID- 2267404 TI - [Computerized tomography and ultrasonography in the study of pedunculated cavernous angioma of the liver. Description of 3 cases]. PMID- 2267405 TI - [Portal thrombosis in puerperium. Description of a case]. PMID- 2267406 TI - [Usefulness of traditional radiography and CT in Gorlin-Goltz syndrome. Description of a case]. PMID- 2267407 TI - [Contribution of radiology in the diagnosis of lymphangiomatosis. Report of a case]. PMID- 2267408 TI - [The role of a shortening osteotomy of the first phalanges associated with soft tissue release in the surgical treatment of hallux valgus]. AB - The Authors report the results of 120 hallux valgus operated on 76 patients from January 1983 to June 1988. The operative procedure associated bunionectomy, tenotomy of the abductor hallucis which was resected from the base of the first phalanx and from the lateral sesamoid, shortening osteotomy of the proximal phalanx and finally adjustment of the sesamoids under the head of the first metatarsal. When there was an important metatarsus varus, a basilar osteotomy of the first metatarsal was associated (10 cases about 120). The results were appreciated functionally (pain, range of motion, easiness for putting on one's shoes) and anatomically (radiological correction of the deformity). The total result included anatomical and functional results. Anatomically, 110 feet had sesamoids perfectly adjusted (that is 92.5 per cent), 9 had an inadequate adjustment (first degree). The metatarsus varus was always improved except 3 cases; in these cases a basilar metatarsal osteotomy would have to be performed. The valgus of the big toe was corrected in 88 per cent of the cases (104 feet had a valgus lower than 15 degrees). A varus of the big toe was found in 6 cases (5 per cent). One was lower than 5 degrees; it was nevertheless included with the good results (very well endured). 5 were more than 10 degrees and were included with the poor results. Finally, we took notice of 4 degenerative changes of the first metatarso-phalangeal joint. The total results found 90 per cent of good and very good results, 6 per cent of fair results and 4 per cent of poor results. PMID- 2267409 TI - Multiple-antigen-mediated autoimmunity (MAMA) in AIDS: a possible model for postinfectious autoimmune complications. PMID- 2267410 TI - Anti-beta 2-microglobulin monoclonal antibodies mediate a delay in HIV1 cytopathic effect on MT4 cells. AB - We attempted to select monoclonal antibodies (mAb) which reacted with T-cell surface molecules and were able to interfere with the human immunodeficiency virus type 1 (HIV1) replicative cycle in the MT4 T-leukaemic cell line. In comparison with OKT4A, an anti-CD4 mAb, only one mAb, HC11.151.1, was found to significantly delay HIV-induced cytopathic effect on MT4 cells among the 15 mAb tested which reacted with MT4 cell surface antigens. Biochemical and immunological characterization of HC11.151.1 demonstrated its specificity for beta 2-microglobulin (beta 2m), the light chain of human leukocyte antigen (HLA) class I molecules. Other beta 2m-specific mAb were tested in order to assess whether this effect represented an intrinsic capacity of HC11.151.1 or whether it was a common feature shared by all anti-beta 2m mAb. Three (B1.1G6, B2.62.2 and BBM1) of the four anti-beta 2m mAb demonstrated the same protective effect, whereas C21.48A, which was devoid of a functional effect, was directed towards a beta 2m epitope involved in binding to the HLA class I heavy chain molecule. The physiological relevance of this observation is discussed. PMID- 2267411 TI - Control of B-cell activation by T-cell lymphokines. PMID- 2267412 TI - A postulated role for the induction of bystander resting B-cell differentiation. PMID- 2267413 TI - Effect of including lasalocid or monensin singly or in combination with furazolidone on the growth and feed consumption of turkey poults. AB - Lasalocid and monensin are widely used to control coccidiosis in broilers, but not in turkey poults. Four feeding trials were conducted to determine the performance of turkey poults when these compounds were used singly or in combination with 100 ppm of furazolidone. Bodyweights and feed consumption were significantly depressed for five weeks after hatching by 150 ppm of lasalocid. Combining furazolidone with lasalocid ameliorated the toxic effect of lasalocid. Bodyweights were significantly depressed by 150 ppm of monensin in the fifth week after hatching, but there was no significant depression in feed consumption. Furazolidone exacerbated any toxic effects of monensin. Data indicate that monensin may be used safely at dosages greater than the recommended level of 60 to 99 ppm, but should not be used in combination with furazolidone. PMID- 2267414 TI - Cardiorespiratory responses to electrical stimulation of the buccal mucosa in ponies. AB - The cardiovascular and respiratory responses to electrical stimulation of the buccal mucosa under general anaesthesia in ponies were measured in order to provide some insight into the cardiorespiratory effects of anaesthesia in equidae. This knowledge may be useful for reducing morbidity during clinical anaesthesia in horses. Anaesthesia was induced with intravenous thiopentone and maintained with 1.3 per cent inspired halothane in oxygen. Arterial blood pressure, heart rate, minute volume, tidal volume, respiratory rate, arterial blood gas tensions and clinical signs of anaesthetic depth were recorded while the buccal mucous membrane was stimulated electrically. A rise in arterial blood pressure was the most consistent response detected along with clinical signs. The response of individual animals varied considerably. Alterations of respiratory pattern sometimes occurred during stimulation but there was no consistent pattern of change in any animal. PMID- 2267415 TI - Glycoconjugate expression in normal hepatoid glands and hepatoid gland adenomas and carcinomas in dogs. AB - Although neoplastic changes in canine hepatoid perianal glands (HPG) are quite common, the biological behaviour is sometimes difficult to assess on the basis of the histopathological examination. In an attempt to detect differences in the glycoconjugate expression between normal and neoplastic HPG, and to verify their relation to the degree of neoplastic progression, normal and neoplastic HPG were studied in 13 dogs, using 11 biotinylated lectins. In HPG adenomas the majority of the cells did not stain or stained weakly after incubation with pokeweed mitogen, LCA and UEA-I. In HPG carcinoma the basal cells lost the specific binding for WGA while heterogeneous distribution of conconavalin-A staining was observed. PMID- 2267416 TI - Effects of cimetidine and ranitidine on basal gastric pH, free and total acid content in pigs. AB - The effects of intramuscular administration of multiple doses of cimetidine and ranitidine on basal gastric pH, free and total acid content from young adult pigs were studied. Cimetidine (4.5 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a simultaneous reduction in free acid content at two, three and 26 hours after the administration of the eighth dose. Ranitidine (0.75 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a concomitant reduction in free acid content at three and 38 hours after the administration of the eight dose. Neither cimetidine nor ranitidine had any significant effects on total acid content. These results confirm that the pig is a basal acid secretor and that the pharmacodynamics and pharmacokinetics of cimetidine and ranitidine in pigs might be different from those in humans. PMID- 2267417 TI - Comparative cell kinetics of avian growth plates. AB - New data on the cell kinetics of the cartilage growth plates in the chicken, budgerigar and rhea derived from studies with tritiated thymidine labelling are given. Quantitative histological measurements on growth plates from leg bones (tibiotarsus, tarsometatarsus and a phalangeal bone) in a further five species of birds are presented. Counts of flat cells and measurements of the average diameter of hypertrophic cells were made for each growth plate. These data are compared with values for the overall growth rates of the bones. The variation in sizes of hypertrophic cells was small and it is concluded that the largest factor in determining the growth rate of an avian bone is the size of the zone of flat cells. PMID- 2267418 TI - Toxocara vitulorum in the milk of buffalo (Bubalus bubalis) cows. AB - The duration of excretion of Toxocara vitulorum larvae in the milk of buffalo cows determines the optimum time for treating calves. Studies on 10 cows showed that a few larvae occur in the colostrum of some cows before the calf has suckled, but most are present from the day after calving and for a further five days. From day 9 onwards, very few larvae were found in the milk. The total number of larvae found was comparable with the number of adult parasites collected from the calves of cows with similar histories. The larvae were 1254 +/ 60 microns long and 36 +/- 6.7 microns in diameter at the ventriculus, figures which are substantially different from some published results. PMID- 2267419 TI - Intravenous solutions for fluid therapy in calf diarrhoea. AB - Five commercially available parenteral solutions were compared for their effectiveness in correcting the disturbances associated with diarrhoea induced by Escherichia coli. Each solution (saline, Hartmann's, Darrow's, Plasmalyte +/- glucose) was tested on eight Jersey calves less than a week old and weighing approximately 25 kg. Each calf received 8.5 litres over three days, at about 20 ml kg-1 h-1. Solutions such as saline or Plasmalyte which had higher concentrations of sodium were more effective at correcting dehydration and electrolyte disturbances than those with less sodium (Darrow's, Hartmann's) but only those with bicarbonate precursors (lactate, acetate, gluconate) were effective in correcting metabolic acidosis. The additional potassium in Darrow's was predictably unhelpful in correcting hyperkalaemia and the additional glucose in Plasmalyte-glucose, despite some beneficial effects, undermined its effectiveness in correcting acidosis. These results suggest that solutions for intravenous treatment should probably contain about 150 mmol litre-1 Na+, 5 mmol litre-1 K+ and about 50 mmol litre-1 of a mixture of bicarbonate and precursors. Neither of the commonly used solutions (saline or Hartmann's) is thus ideal. PMID- 2267420 TI - Subcellular distribution of copper in the liver of fetal deer in the last month of gestation. AB - Fetal deer, in the last month of gestation, accumulate high concentrations of copper in the liver. Livers from fetal deer in late gestation were homogenised and fractionated by continuous sucrose density gradient centrifugation. The distribution of copper closely followed that of DNA; approximately two thirds of the metal was localised to the nuclear fractions with the remaining third in the cytosolic fractions. The fractionation procedure was repeated with digitonin, a lysosomal perturbant: lysosomes were disrupted and the marker enzyme, N-acetyl beta-glucosaminidase, shifted from the particulate fractions to the cytosolic fractions; the distribution of copper was unaffected. Differential centrifugation of homogenate confirmed that approximately two thirds of the copper was associated with the nuclear fraction. Further confirmation of a nuclear localisation of copper was provided by X-ray microanalysis of purified nuclei. PMID- 2267421 TI - Effect of ostertagiasis on copper status in sheep: a study involving use of copper oxide wire particles. AB - Lambs infected with Ostertagia circumcincta larvae and uninfected controls were either doses with 5 g copper oxide wire particles (COWP) or remained undosed. The change in abomasal pH was monitored from duodenal digesta and that in liver copper concentration from initial liver biopsy samples and liver obtained at necropsy after 22 days. Infection increased the pH of digesta from 2.5 to 4.5. The change in liver copper content in sheep not treated with COWP was +6.1 mg (12.6 per cent) and -6.8 mg (13.8 per cent) in control and infected sheep, respectively. Significantly greater amounts of COWP were recovered from the abomasa of infected than from control animals (3.6 +/- 0.23 and 1.6 +/- 0.55 g, respectively) and hepatic uptake of copper from COWP was 0.7 and 1.8 per cent of the dose, respectively. There were significant relationships between the pH of duodenal contents and COWP retained, soluble copper concentration in duodenal digesta and hepatic uptake of copper. It was concluded that, through causing an increase in pH in abomasal and duodenal digesta, gastrointestinal nematodes interfere with copper metabolism. PMID- 2267422 TI - Characterisation of compounds isolated from the sera of horses with acute grass sickness. AB - Isolates were prepared from the sera of 12 horses with acute grass sickness, using methods reported to yield serum fractions associated with neurotoxicity, and their components identified by liquid chromatography and spectroscopy. All isolates were found to contain cortisol and six isolates also contained a degradation product of an analgesic drug, dipyrone. However, no recognised neurotoxin was detected. PMID- 2267423 TI - Assessment of respiratory diseases and therapeutic intervention by the forced oscillation technique in feedlot cattle. AB - The forced oscillation technique was used to study pulmonary function in bulls during naturally acquired pulmonary-gastrointestinal disease complex known as shipping fever and as it was treated with two different antibiotics. Fifteen double-muscled bulls of the Belgian White and Blue breed were investigated. Clinical, serological and pulmonary function values were recorded during and after naturally occurring respiratory disease. Total respiratory resistance (Rrs) and reactance (Xrs) were measured by the forced oscillation technique. The antibiotic ceftiofur (group A, n = 10) and oxytetracycline (group B, n = 5) were given over three days. A large increase of Rrs at low frequencies with a marked negative frequency dependence, an increase of the resonant frequency, and a decrease of Xrs were recorded in the initial stage of the disease. The parameters returned to normal values seven days later. Clinical evidence of recovery was more marked in group A than in group B. These results show that moderate shipping fever induces acute small and large airway obstruction which responds to appropriate antibiotic therapy. PMID- 2267424 TI - Preliminary studies on the use of propofol in the domestic pigeon (Columba livia). AB - The anaesthetic propofol was investigated in domestic pigeons (Columba livia). The agent was administrated intravenously, in one group of birds as an adjunct to ketamine hydrochloride, and careful monitoring was performed. The dose of 14 mg kg-1 of propofol was based on allometric scaling for its use as a sole agent. Propofol anaesthesia was characterised by smooth rapid induction and good muscle relaxation but was only of short duration, ranging from two to seven minutes, and seemed to cause a marked respiratory depression. Indeed, a very narrow safety margin for propofol was observed in pigeons when ventilation was not assisted. The agent may have applications in avian anaesthesia but these are likely to be limited. PMID- 2267425 TI - Immunohistochemical demonstration of Mycoplasma gallinarum and Mycoplasma gallinaceum in naturally infected hen oviducts. AB - Using indirect immunoperoxidase (IIP), peroxidase anti-peroxidase (PAP) and avidin biotin-peroxidase complex (ABC) immunohistochemical methods, Mycoplasma gallinarum and M gallinaceum antigens were demonstrated in ethanol-fixed paraffin embedded oviduct sections from hens the eggs from which showed suboptimal hatchability. Specific immunoperoxidase staining was detected at the mucosa in the magnum portion of the oviduct. Optimal staining was achieved by applying the ABC method, though both IIP and PAP methods can also be used for diagnosis. Isolation and identification techniques gave similar results for the species of avian mycoplasmas involved. PMID- 2267426 TI - Concurrent infection with Theileria buffeli caused depression of parasitaemia in Babesia bovis and Anaplasma centrale infections in splenectomised calves but not in B bigemina infections. AB - In five experiments undertaken in splenectomised calves it was found that Theileria buffeli infections depressed the parasitaemias of superimposed Babesia bovis and Anaplasma centrale infections, but not B bigemina infections. The course of A centrale infections did not appear to be affected by a concurrent Eperythrozoon teganodes infection. PMID- 2267427 TI - Toxic effects for lambs of cytotoxic necrotising factor from Escherichia coli. AB - The lethal effect, clinical signs and lesions caused by the intravenous inoculation into six lambs (seven to 10 days old) of a partly purified preparation of cytotoxic necrotising factor (CNF) from Escherichia coli, strain BM2-1, were investigated. Two control preparations were also tested in two lambs each: (i) the same as above but heated for one hour at 60 degrees C, a treatment which inactivates CNF and preserves residual endotoxic activity; and (ii) purified material from a CNF-defective mutant of BM2-1. Whereas none of the lambs in either of the control groups died or showed significant clinical signs or lesions, all the lambs inoculated with partly purified CNF developed severe clinical signs starting six hours after inoculation which consisted mainly of neurological signs and mucoid diarrhoea. The most striking lesions were oedema and haemorrhages in the central nervous system, and foci of coagulation necrosis in the myocardium. Mucus hypersecretion in the gastrointestinal tract was not associated with cellular inflammation. PMID- 2267428 TI - Lectin histochemistry of the central nervous system in a case of feline alpha mannosidosis. AB - The diagnosis of feline alpha-mannosidosis is made by demonstrating deficient activity of the enzyme alpha-mannosidase or an elevation of its undergraded substrate in body fluids or tissue. In this study the storage of specific sugar residues in the brain and spinal cord in a case of feline alpha-mannosidosis was examined by means of nine different biotinylated lectins and the avidin-biotin peroxidase method on formalin-fixed, paraffin-embedded tissue sections. The lectin staining pattern strongly correlated with the known biochemical findings of the stored oligosaccharides in feline alpha-mannosidosis and was different from the lectin reactivity of normal cat tissues. This confirms that lectin histochemistry is a simple, relatively inexpensive and reliable method for diagnosing alpha-mannosidosis in cats. PMID- 2267429 TI - Efficacy of epsiprantel against Echinococcus granulosus infections in dogs. AB - Dogs with 41-day-old experimental infections of Echinococcus granulosus were treated orally with epsiprantel. Single doses of 2.5 mg kg-1, 5.0 mg kg-1 or 7.5 mg kg-1 were effective in removing more than 99 per cent of these parasites, but total clearances of worms only occurred in dogs given the highest dose. PMID- 2267430 TI - [The role of endothelium-derived contracting factor (EDCF) and endothelium derived relaxing factor (EDRF) in the aorta of the rat: identification of EDCF]. AB - The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The rings of the thoracic aorta were obtained from age-matched SHR and WKY, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the rings from SHR were significantly weaker than those obtained in WKY. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase-inhibitor (indomethacin) or thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) both in the SHR and WKY rings. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholine-induced relaxation in the rings from SHR or WKY. In the organ bath solution, following acetylcholine stimulation, prostaglandin E2 and 6-keto-prostaglandin F1 alpha concentrations increased, but prostaglandin F2 alpha and thromboxane B2 concentrations did not increase. Exogenous prostaglandin H2, a stable analogue of thromboxane A2 (STA2) and prostaglandin F2 alpha induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2 and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endothelium-derived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in that of WKY. The results also suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation. PMID- 2267431 TI - [Fall in aortic diastolic pressure immediately after aortic valve destruction can predict severity of regurgitation through the valve and chronic morphological changes in the left ventricle]. AB - Aortic regurgitation (AR) has been studied experimentally, however these reports did not investigate compensatory mechanisms in AR in relation with the severity of regurgitation. If the severity of AR can be changed voluntarily, we can evaluate the pathophysiological response to AR in wide range. The purposes of this study were 1) to see if the extent of fall in aortic diastolic pressure immediately after the production of AR (delta AoDP) was a reliable predictor of the severity of AR and 2) to evaluate the process of adaptation through acute and chronic stage in moderate AR in the rabbit model. AR was produced by perforating the aortic valves in Japanese white rabbits. First, aortic pressure, volume, weight and wall thickness of the left ventricle were measured. Correlations between delta AoDP and body weight-corrected volume (LVV/BW) and weight (LVW/BW) were studied in 18 rabbits soon after, 19 one week after, 23 four weeks after and 10 eight weeks after the production of AR. delta AoDP was closely correlated with LVV/BW after 1 week (1 week: R = 0.667, p less than 0.01, 4 weeks: R = 0.733, p less than 0.01, 8 weeks: R = 0.757, p less than 0.05) and with LVW/BW after 4 weeks (4 weeks: R = 0.484, p less than 0.05, 8 weeks: R = 0.651, p less than 0.05). The slope of these regression equations increased with time (delta AoDP and LVV/BW: 1 week: 0.0138, 4 weeks: 0.0361, 8 weeks: 0.0577 ml/kg.mmHg; delta AoDP and LVW/BW; 4 weeks: 0.0142 8 weeks: 0.0310 g/kg.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267432 TI - [Regional myocardial coronary blood flow reserve in hypertrophic cardiomyopathy assessed by digital subtraction coronary angiography]. AB - Previous observations suggest the presence of ischemia in the disproportionately thickened interventricular septum (IVS) of patients with hypertrophic cardiomyopathy (HCM), although the details remain obscure. Utilizing digital subtraction coronary angiography (DSA) with LAO projection before and after intracoronary papaverine (P) injection, we evaluated regional myocardial coronary blood flow reserve (rMFR) consecutively 18 patients with HCM, and compared it with that of 8 patients without apparent cardiac abnormality (C). Time-density curves were obtained from digital angiograms of the myocardial region of interest. We measured peak contrast density (Cm) and time to peak contrast (Tm). An index of rMFR was calculated as the quotient of Cm/Tm before and after P. In HCM, rMFR in IVS and apex was significantly lower than that of C (Mid-IVS: 1.9 +/ 0.5 vs 3.9 +/- 0.5, p less than 0.001; Low-IVS: 2.0 +/- 0.5 vs 4.4 +/- 0.9, p less than 0.001; Apex: 2.0 +/- 0.7 vs 4.5 +/- 1.6, p less than 0.01). There was correlation between the impairment of rMFR and the extent of hypertrophy in HCM. In conclusion, we could state that, in HCM, the region of impaired myocardial coronary blood flow reserve is localized. In HCM, DSA is useful in evaluating myocardial coronary blood flow reserve. PMID- 2267433 TI - [A case report of redo A-C bypass for MCLS performed 13 years after initial surgery]. AB - This is the first report of re-aortocoronary bypass for Kawasaki's disease. The patient is a 22-year old female. She was afflicted with Kawasaki's disease at the age of 6 and had the symptom of angina pectoris at the age of 9. She went through the first aortocoronary bypass, to the left anterior descending artery (LAD) and the right coronary artery (RCA) with saphenous vein graft (SVG). After the first operation, the graft to LAD occluded totally, but she remained asymptomatic and well for 11 years. She had a sudden recurrence of anginal attack at the age of 20. The examinations confirmed ischemia of the anterior wall (LAD area) and the lateral wall (LCX area). Coronary angiography revealed patent SVG with a moderate sign of sclerotic change. We decided on re-aortocoronary bypass, left mammary artery to LAD and gastroepiploic artery to LCX, when she was 22-years old. LIMA was anastomosed to LAD, but LCX was not revascularized, because LCX was not identified and exposed in the operation. In spite of incomplete revascularization, postoperative stress ECG test was negative. Tl-myocardial scintigram confirmed no ischemia of the anterior wall and greatly reduced ischemia in the lateral wall. She became asymptomatic and returned to normal life. PMID- 2267434 TI - [A case report of corrected transposition of the great arteries without any associated defects in a 36-year-old man and the review of adult cases reported in Japan]. AB - We report a case in a 36-year-old man of corrected transposion of the great arteries (CTGA) without any associated defects. We also review clinical characteristics and later complications of adult CTGA cases reported in Japan. The patients was referred to our hospital for further examination of the abnormal ECG found during regular medical check-up. His ECG showed left axis deviation, first degree AV block, abnormal Q waves in the left precordial leads, and disappearance of septal q waves in the left precordial leads. His exercise capacity was found to be more than 12 METS by treadmill exercise testing. His roentgenogram revealed an egg-shaped ventricle with normal CTR (45%). The following findings were obtained by two-dimensional echocardiogram and heart catheterization: 1) the functional left ventricle had the characteristics of the anatomical right ventricle, 2) The positions of the left and right atrioventricular valves were reversed, 3) Other cardiac anomalies such as VSD, pulmonary stenosis, tricuspid regurgitation (TR) were not proved. Therefore, he was diagnosed as having CTGA without any cardiac defects (SLL type). At present, with ages more than 15 years, 36 cases of CTGA without cardiac anomalies have been reported in Japan including this case. But most cases had significant TR. This case was the 7th reported case without the accompaniment of TR. Among 36 cases, TR was found in 71%, complete AV block in 20%, and congestive heart failure was noted in 45%. Prognosis of CTGA without any defects is dependent on the appearance of TR, advanced AV block, and congestive heart failure. As these later fatal complications are observed very often, it is important to detect the patient of CTGA accurately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267435 TI - [A case of successfully managed acute asthmatic attack by cervical epidural block during mechanical ventilation]. AB - A 47-year-old male suffering from an acute asthmatic attack was admitted in the morning. He was arrested on arrival. Following successful resuscitation, he was treated by using controlled ventilation with a Bennett 7200 respirator. Before starting mechanical ventilation, he was physically exhausted and had carbon dioxide retention (PaCO2 76.2 mmHg). The patient received dexamethasone 40 mg/day and theophylline 400 mg/day during the first 4 days. Despite the decrease in PaCO2 following mechanical ventilation, cycling pressure remained high (up to 50 70 cmH2O) even after 24 hours. Because of the risk of barotrauma due to high cycling pressure, we conducted cervical epidural block to reduce airway hyperreactivity to the endotracheal tube and endotracheal suctioning. Six to 10 ml of lidocaine with 1:200,000 epinephrine was administered every 1 or 2 hours. Within 4 hours after epidural block, airway pressure decreased to 30-40 cmH2O. Since then, requirements of sedative (diazepam) have decreased greatly to 10 mg/day. The patient was successfully extubated 4 days after admission. Finally, epidural block was continued for 6 days without any complication. We do not know how cervical epidural block works to reduce airway pressure. It might be beneficial to manage patients artificially ventilated during asthmatic attack. PMID- 2267436 TI - [Tetralogy of Fallot revealed by autopsy in an elderly subject]. AB - A 62-year-old women had a history of cyanosis and easy fatigability from school age but had refused medical examinations. She was admitted to our department with exacerbation of dyspnea at the age of 59. Laboratory tests showed hypoxia complicated with polycythemia with 35 mmHg of PaO2, 8.5 x 10(6) erythrocytes per mm3. The systolic pressure of the right ventricle was 155 mmHg. RI angio demonstrated a high degree of the right-to-left shunt at the ventricular level. The patient was given oxygen therapy at home without diagnosis of tetralogy of Fallot (TOF) and eventually died at the age of 62. Tetralogy of Fallot was diagnosed at autopsy. Pulmonary stenosis of this case was located in infundibulum. The lining of the infundibular inlet was constituted of the thick fibrous tissue which remarkably augmented the pulmonic stenosis. Although the autopsy findings were considered to be relatively mild TOF, the death was presumed to be caused by development of the infundibular stenosis due to formation of fibrous tissue. This is the oldest patient in Japanese medical literature to be identified by cardiac catheterization and autopsy finding as a case of TOF. PMID- 2267437 TI - [Hypoxia and ATP synthesizing system]. PMID- 2267438 TI - [Survival and functional results after valve replacement]. PMID- 2267439 TI - [Quantitative measurement of dyspnea]. PMID- 2267440 TI - [Dipyridamole stress test]. PMID- 2267441 TI - [Congenital heart disease and post operative arrhythmias]. PMID- 2267442 TI - [Noncontact noninvasive measurement of mechanocardiography and pulse wave velocity by microwave Doppler sensor]. PMID- 2267443 TI - [Membranous glomerulonephritis. Experience at the Instituto Nacional de la Nutricion Salvador Zubiran]. AB - The purpose of this retrospective study was to study the incidence of idiopathic and secondary forms of membranous nephropathy in our institution, its clinical course and progression to chronic renal failure, and the risk factors associated with it. Two hundred fourteen (16%) of the 1,287 renal biopsies obtained between 1962 and 1988 were primary glomerular diseases and 28 of this 214 (13%) were idiopathic membranous nephropathy. On the other hand 59 of 1,287 biopsies were membranous nephropathy of whom 28 were idiopathic, 27 secondary to systemic lupus erythematosus, 2 due to drugs, one associated with rheumatoid arthritis, and one more with breast cancer. The clinical picture was: nephrotic syndrome in 84%, hypertension in 15%, non-nephrotic proteinuria in 14%, chronic renal failure in 8.4%, and renal vein thrombosis in 6.3%. In the idiopathic group 75% of the patients were male while in the lupus group 85% were female. For the analysis of progression to chronic renal failure we excluded 5 patients with renal failure when the biopsy was taken, 2 because the nephropathy was due to drugs, one associated with breast cancer, and nine were within the first year of follow-up. Thus, for this analysis the group consisted of 22 patients with idiopathic form and 20 with systemic lupus erythematosus. The idiopathic and lupus groups were similar except for a lower serum albumin in the former. The progression to renal failure was seen in 9 patients: six in the idiopathic group and the other 3 in the lupus group; this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267444 TI - Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. II. In vitro release of renin, angiotensinogen and aldosterone. AB - In vitro release of renin, angiotensinogen and aldosterone was studied in control (CT) and nephrotic rats. Nephrotic syndrome (NS) was induced by a single injection of puromycin aminonucleoside (PA). The in vitro systems used were: renal cortical slices (RCS), liver slices (LS) and adrenal glands, all incubated in Krebs-Ringer buffer. Renal renin content (RRC) and isoproterenol-induced renin secretion (RS) also were studied. RS, RRC and angiotensinogen release were measured indirectly by radioimmunoassay (RIA) of angiotensin I (ANG I); aldosterone was estimated by direct RIA. Basal RS was not modified in NS: 385 +/- 196 (CT) vs 344 +/- 149 ng ANG I/mg protein/h (NS), p greater than 0.05. Isoproterenol increased RS significantly in both CT and NS groups: 535 +/- (CT) and 685 +/- 231 ng ANG I/mg protein/h (NS) (p less than 0.05 vs. basal RS). RRC was similar in both groups: 2.17 +/- 0.62 (CT) vs 2.05 +/- 0.49 micrograms ANG I/mg protein/h (NS), p greater than 0.05. Angiotensinogen release from LS increased in nephrotic rats from 10 +/- 3.2 (CT) to 12 +/- 1.9 pmoles angiotensinogen I/mg tissue/2h (NS), p less than 0.05. Aldosterone release increased markedly from adrenal glands of rats with NS (1649 +/- 1111 pg aldosterone/mg tissue/h) with respect to control rats (257 +/- 85), p less than 0.05 In vitro studies were performed six days after PA-injection, when nephrotic rats had ascitis, edema, proteinuria, hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, low sodium and aldosterone excretion, low levels of plasma angiotensinogen and high levels of plasma renin and aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267446 TI - [Familial acute leukemia. Report of 7 cases in 3 families]. AB - Seven members of 3 families developed acute leukemia (AL) between 1969 and 1988. The clinical presentation, course and response to treatment were no different to non-familial cases of AL. The morphology subtypes were identical in every family: myeloblastic in 3 and lymphoblastic in 4. Leukemogenic factors (radiation, drugs use or benzene exposure) were excluded in these patients. Genetical and environmental factors might have a role in the pathogenesis but no clear evidence has been established. PMID- 2267445 TI - [Unilateral lung transplant in a case of terminal pulmonary fibrosis]. AB - Up to 1980, less than 40 lung transplants had been reported worldwide without any success. The factors influencing these poor results were related to complications at the bronchial anastomosis and ineffective immunosuppressive regimens. The development of new immunosuppressive drugs has permitted the reevaluation of lung transplantation as a therapeutic option. The success with heart-lung transplantation stimulated the development of clinical human single-lung and double-lung transplantation. However the world experience is still scarce. In our institution we have developed experimental work leading to the establishment of a lung transplant program. This paper describes our first single lung transplant patient. The patient, a 33 year old man with end-stage pulmonary fibrosis, was totally oxygen dependant, maintaining arterial blood oxygen levels below 40 mmHg without oxygen supplementation and confined to a wheelchair. A single left lung transplant was performed from a young brain-dead donor. The bronchial anastomosis was protected with an omental flap. The immunosuppressive regimen was based on cyclosporin A and azathioprine from the beginning, adding prednisone on the third postoperative week. There has been only one episode suggestive of acute rejection which was managed with methylprednisolone. On the 9th postoperative week the patient developed a bronchial stenoses at the anastomotic site which required dilation and stenting with an endobronchial silastic stent. His clinical course has been uneventful since then. His ventilatory parameters showed an increase of vital capacity from 900 to 2100 mL and his FEV1 from 700 to 1500 mL. His gas exchange has been normal with arterial blood gas oxygen above 60 mmHg and oxygen saturation above 94%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267447 TI - [Cystadenocarcinoma of the appendix. Report of a case]. AB - Primary adenocarcinoma of the appendix is an uncommon disease frequently diagnosed surgery. It has an occurrence between 0.01 and 0.11% of all appendectomized patients, and it is more often found in patients older than fifty years. Symptoms are usually similar to those seen in acute appendicitis. Some authors consider the mucocele of the appendix a primary carcinoma as it is related with obstruction of the appendix lumen followed by a cystic dilatation with mucosal changes, mucus hypersecretion and extension outside of the appendix. We present one case with abdominal pain, constipation, weight loss of 26 kg, and a mass localized in the right lower quadrant. An exploratory surgery showed a partially retroperitoneal mass of 15 by 20 cm, irregular, cystic, with mucus content and the appendix included in it. The mass was removed and appendectomy was performed. Postoperatively the patient did well. The final pathologic report was a cystadenocarcinoma of the appendix. PMID- 2267448 TI - [Dacie syndrome and other splenomegalies without apparent cause]. AB - Some enlarged spleens do not seem to be related with known pathogenetic mechanisms (passive congestion, functional workload, malignant infiltration and inflammatory or storage disorders). Non-tropical idiopathic splenomegaly (Dacie's syndrome) is a form of hypersplenism of unknown origin that evolves into a non Hodgkin lymphoma, after a variable interval, in 20% of the patients. Tropical idiopathic splenomegaly (or hyperreactive malarial splenomegaly) develops when a chronic malarial challenge triggers an abnormal immunological response consisting in decreased suppressor T lymphocytes and increased amounts of circulating immunoglobulin M and immunocomplexes, which are cleared by the splenic macrophages. This peculiar response to malaria seems to be linked to particular HLA antigens. Other confusing splenomegalies are seen in Felty's syndrome, in populations subjected to recurrent infections, and in some families. Overlapping findings and diseases suggest chronic antigenic stimulation as a common feature, with diverse responses depending on the host. A small percentage (probably less than 3%) of normal individuals has minimal splenomegaly without any clinical significance. PMID- 2267450 TI - [A new strategy for post-graduate medical education. I]. PMID- 2267449 TI - [Carpal tunnel syndrome]. PMID- 2267451 TI - [Evaluation of pipetting systems. II. Precision and accuracy of precision dispensers]. AB - OBJECTIVE: To evaluate the precision and accuracy of the liquid dispensers being used in our institution. MATERIAL: A total of 15 dispensers (8 micro and 7 macro) of automatic, semiautomatic or manual types were evaluated. They had been in use from 0.5 to 7 years. METHODS: The volume dispensed was established by gravimetry using an analytical balance (Chio JP-160) and deionized distilled water as previously described. The microdispensers were evaluated using volumes of 20 and 100 microL, and the macrodispensers with 1 and 5 mL. Each dispenser was evaluated using 10 replicates: the mean and the CV (coefficient of variation) were calculated with the 10 replicates. The mean was transformed to per cent of the theoretical volume. Thus a 100% ratio of accuracy corresponds to a perfect accuracy. An important methodological aspect was that the 10 dispensing replicates were performed personally by the habitual user of the dispenser. RESULTS: The mean and CV are shown in table 2 for the microdispensers, and in table 3 for the macrodispenser. In the total 25 evaluation in tables 2 and 3 there were 8 instances in which precision was poor (CV above 3%) and also 8 cases of sizable inaccuracy (ratio outside of 100 +/- 5%). In 4 (2 micro and 2 macro) of these 8 inaccuracies, the error ranged from 10% to 22%. A minority was within the specifications of precision and accuracy claimed by the manufacturers of the dispensers with the exception of the manual microdispensers which were within specifications in most instances. We attribute the latter to the lack of a mechanical device in the manual dispensers. CONCLUSIONS: As in a previous evaluation of automatic micropipettes, we detected a high proportion of pipetting systems out of specifications in both precision and accuracy. The magnitude of error in the accuracy of 4 dispensers (10 to 22%) would be catastrophic in methods demanding good pipetting. PMID- 2267452 TI - [In the treatment of acute leukemia results as good as those in developed nations are being obtained, nevertheless...]. PMID- 2267453 TI - [Leukemia and malnutrition. II. The magnitude of maintenance chemotherapy as a prognostic factor in the survival of patients with standard-risk acute lymphoblastic leukemia]. AB - In previous papers we have shown that malnutrition is an adverse prognostic factor in the outcome of treatment in patients with standard-risk acute lymphoblastic leukemia. The reason why undernourished children do poorly as compared with well nourished children is that malnourishment leads to a diminished bone marrow reserve thus making necessary to delivery of suboptimal doses of maintenance chemotherapy (less than that calculated according to body surface). Undernourished children receive less 6-MP and MTX and relapse more frequently in the bone marrow, finally reflecting a 5 yr disease-free survival of 26% as compared with 83% in well-nourished children (p less than 0.001). In this paper we have analyzed the impact of the variable delivery of sub-optimal doses of maintenance chemotherapy in a group of 43 pediatric patient with standard-risk acute lymphoblastic leukemia. The 5 year disease free survival of children receiving suboptimal maintenance chemotherapy was 7% as compared with 65% for those receiving full doses of both 6-MP and MTX (p less than 0.001), and more frequent relapse involving the bone marrow in children receiving low doses (71% versus 3%, p = 0.000005). The impact of the variable suboptimal doses of chemotherapy was present in children with both normal and deficient nourishment status. It is concluded that the delivery of suboptimal doses of maintenance chemotherapy, due to bone marrow toxicity related to an abnormal myelopoietic reserve, is an adverse prognostic factor in the outcome to treatment of patients with lymphoblastic leukemia. PMID- 2267454 TI - Amikacin nephrotoxicity in patients with chronic liver disease. AB - Chronic liver disease is a risk factor for aminoglycoside nephrotoxicity. We conducted this study to identify the incidence and risk factors associated with it. A total of 45 patients with liver disease and 329 controls were included, with a toxicity incidence of 17.7%, similar to that in controls. Chronic liver disease patients received lower amikacin doses than calculated on the basis of creatinine clearance (498 +/- 1187 vs 611 = 313 mg/day). Serum albumin, both at the beginning of the treatment and at the end was lower in patients who developed toxicity, and bilirubin levels were higher in these patients at the end of the treatment. Apparently, a dose reduction may lessen the risk for amikacin nephrotoxicity in patients with chronic liver disease. We conclude that hypoalbuminemia and hyperbilirubinemia are risk factors in this complication. PMID- 2267455 TI - [Tamoxifen as initial treatment in breast cancer in elderly women: a 10-year follow-up]. PMID- 2267456 TI - [Radiotherapy of breast cancer and preparation of the patient]. PMID- 2267458 TI - [Infectious dermatoses in athletes]. PMID- 2267457 TI - [Diagnosis of asymptomatic urinary infections in pregnant women by detection of leukocyte esterase]. PMID- 2267460 TI - [The detection of child abuse: prospective evaluation of one year (April 89-end of March 90)]. PMID- 2267459 TI - [Physiopathology of oxygen transport. Determinants of hypoxia]. PMID- 2267461 TI - [Recovery in psychiatry]. PMID- 2267462 TI - [Peri-mortality and peri-thanatology]. PMID- 2267463 TI - [The pathogenesis of decompression sickness]. PMID- 2267464 TI - [Physiopathological basis and methods in the measurement of dyspnea]. PMID- 2267465 TI - [The physiopathology of asthma]. PMID- 2267466 TI - [Human recombinant erythropoietin: from clinical aspects to the physiopathology of anemia of renal insufficiency]. PMID- 2267467 TI - [Of mice and men: or a mouse reveals the physiopathology of globoid cell leukodystrophy (Krabbe's disease)]. PMID- 2267468 TI - [Renal tubular acidosis in children]. PMID- 2267469 TI - [Pathogenesis of cerebral lesions in newborn infants]. PMID- 2267470 TI - [Regulation of gastric acid secretion]. PMID- 2267471 TI - [Botulinum toxin A in ophthalmology and neurology: our clinical experience over more than 4 years]. PMID- 2267472 TI - [Management of persons infected with HIV by medical practitioners in the canton of Vaud]. PMID- 2267473 TI - Vasoactive intestinal polypeptide induces REM recovery in insomniac forebrain lesioned cats. AB - Basal forebrain (BF) lesions in cats produces insomnia by reducing both slow wave sleep (SWS) and rapid-eye-movement (REM) sleep time. Recently it has been shown that vasoactive intestinal polypeptide (VIP) may be a specific REM inductor in the parachlorophenylalanine (PCPA) insomniac model. The purpose of this study was to test the hypnogenic properties of VIP in a nonpharmacological model of insomnia. Cats were rendered insomniac by delivering a DC current through stainless steel tripolar electrodes implanted in the basal forebrain area (BFA). Sleep-waking cycle recordings were done prior to lesions and on days 7, 9, 10, 11, 14, and 21 days after BF lesion. On day 10 after the lesion, 200 ng of VIP was injected into the 4th ventricle. Results showed that on postlesion days 7 and 9, SWS and REM sleep total times decreased, while waking time increased significantly. VIP restored REM sleep total time and frequency for almost 48 h, and SWS sleep total time for 24 h. On days 14 and 21 postlesion, insomnia was reestablished. Results are discussed in terms of the possible anatomical and neurochemical substrates whereby VIP can induce the recovery of sleep-waking control values. PMID- 2267474 TI - Correlations between cardiorespiratory measures in normal infants and victims of sudden infant death syndrome. AB - Coordination between physiological measures (i.e., the tendency for measures to co-vary with each other) develops with maturation in the infant. We hypothesized that correlations between cardiorespiratory measures would increase with maturation in normal infants and that infants destined to die of sudden infant death syndrome (SIDS) would show lower correlations than those of age-matched controls. Twenty-two recordings of electrocardiogram and respiratory movements were obtained from infants who subsequently succumbed to SIDS and compared with 66 recordings from control infants. Each 1-min epoch of data was sleep-state classified. Median heart and respiratory rate, respiratory variability, and median extent of three types of heart rate variation were determined for each epoch, and the minute-by-minute correlations between seven pairs of parameters were determined for quiet sleep, rapid eye movement sleep, and waking in each recording. Most cardiorespiratory measures showed correlations that increased with age; the correlation coefficients for these measures tended to be lower in SIDS victims than in controls prior to 2 weeks of age. The correlations between heart rate and heart rate variability became lower with maturation; correlations between these measures tended to be higher in the SIDS victims. In all analyses showing significant maturational trends, the SIDS victims showed "less mature" correlations than those of the controls. PMID- 2267475 TI - Evidence for genetic influences on sleep disturbance and sleep pattern in twins. AB - The etiologic role of genotype and environment in sleep pattern (daytime napping, habitual bedtime, and sleep duration) and subjective sleep quality and sleep disturbance was examined using a general population sample of 3,810 adult Australian twin pairs, aged 17-88 years. Genetic differences accounted for at least 33% of the variance in sleep quality and sleep disturbance and 40% of the variance in sleep pattern. There was no evidence for a decline in the importance of genetic predisposition with age. Short-term environmental fluctuations accounted for as much as 30% of the variance, and more stable nonfamilial environmental effects accounted for the remainder. No effect of shared family environment on sleep characteristics was found. PMID- 2267476 TI - DR2-positive monozygotic twins discordant for narcolepsy. AB - Narcolepsy runs in families, and recent research has revealed the human leukocyte antigen (HLA) DR2 to be a genetic marker closely associated with the disease. But, as indicated by family studies, other factors contribute to the pathogenesis of narcolepsy. The investigation of monozygotic twins is the most specific research tool for distinguishing between a multigenetic and a multifactorial pathogenetic model. We present clinical and sleep polygraphic data from two pairs of monozygotic twins, and in addition, from some of their first-degree relatives. In both pairs only one twin suffered from the clinical symptoms of narcolepsy/cataplexy. Only in these subjects did night sleep recordings and a multiple sleep latency test reveal both multiple sleep onset rapid-eye-movement periods (SOREMPs) and short mean sleep onset latencies. However, in two of the asymptomatic, HLA DR2+ relatives, short mean sleep onset latencies during the multiple sleep latency test (MSLT) were observed, and one, HLA DR2- relative showed REM sleep two times during the MSLT. Our results strongly favor a multifactorial pathogenetic model for narcolepsy. PMID- 2267477 TI - Screening for subclinical sleep-disordered breathing. AB - We evaluated self-administered questionnaires and short sleep studies in screening for sleep-disordered breathing (SDB) in 40 hypertensive men ages 36-66 unselected for symptoms. Each subject completed a questionnaire including questions on sleep-related symptoms and underwent overnight polysomnography in which we evaluated the apnea-hypopnea index (AHI) and the percentage of time during which arterial O2 saturation was less than 90% (T90). The first 90 min of overnight study was evaluated separately, and 10 subjects with an AHI greater than or equal to 10 also underwent late afternoon nap study. By overnight polysomnography, 48% of the cohort had an AHI greater than or equal to 10, and 35% had a T90 greater than or equal to 10%. Using linear regression, we found no features of the symptom questionnaire that strongly predicted AHI. Only self reported snoring and baseline arterial Po2 significantly predicted T90. The AHI and T90 were not significantly correlated. Considering an AHI greater than or equal to 10 in the overnight study as "abnormal" and an AHI greater than or equal to 10 on the short study as a "positive" test, the specificity of the AHI in the first 90 min was 100% (21/21), and the sensitivity was 42% (8/19). The sensitivity of the nap study was 60% (6/10). We conclude that in a cohort unselected for symptoms, the ability of self-administered questionnaires to predict SDB was low; short studies were only moderately sensitive for detecting an AHI greater than or equal to 10, and the AHI was not a major determinant of nocturnal desaturation. PMID- 2267478 TI - Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome. AB - Bright light has recently been shown to have phase-shifting effects on human circadian rhythms. In this study we applied this effect to 20 patients with delayed sleep phase syndrome (DSPS) who were unable to fall asleep at conventional clock times and had a problem staying alert in the morning. In a controlled treatment study, we found that 2 h of bright light exposure in the morning together with light restriction in the evening successfully phase advanced circadian rhythms of core body temperature and multiple sleep latencies in these patients. This finding corroborates the importance of light for entraining human circadian rhythms. PMID- 2267479 TI - Nocturnal stridor in olivopontocerebellar atrophy. AB - We describe a patient with olivopontocerebellar atrophy (OPCA) who was referred for alleged "snoring." Polysomnogram with video and audio monitoring revealed that the patient actually had nocturnal stridor causing repetitive oxygen desaturations. Direct laryngoscopy while awake showed a unilateral vocal cord paralysis. The nocturnal stridor persisted after unilateral vocal cord pinning, suggesting that the patient had probably been experiencing bilateral vocal cord paresis while asleep. We conclude that state-dependent vocal cord dysfunction may be severe in OPCA and related multiple system atrophy. Nocturnal stridor has many causes and may mimic snoring and obstructive sleep apnea syndrome. Polysomnography with audio and video recordings are necessary to make the diagnosis. PMID- 2267480 TI - Alpha EEG sleep produced by balloon catheterization of the esophagus. PMID- 2267481 TI - Bacteremia due to Escherichia coli: a study of 861 episodes. AB - Escherichia coli accounted for 861 (23.9%) of 3,605 episodes of bacteremia in an 18-year prospective survey at St. Thomas' Hospital, a proportion that changed little during the survey. The most common focus of infection leading to nosocomial and community-acquired bacteremia due to E. coli was the urinary tract. Twenty-six percent of adult female patients with E. coli bacteremia resulting from a urinary tract infection were diabetic. The O antigen serotypes identified most often were O6, O2, O1, O4, O15, and O75; the multiply resistant O15 serotype of E. coli was implicated in a community outbreak of urinary tract infection. Ampicillin resistance in strains causing community-acquired infection increased to the same level as that of strains causing nosocomial infection (almost 50%). The overall mortality was 20.7% and was greater in the presence of shock (52.4% vs. 15.3%). Death due to infection occurred in 2.6% and 10.3%, respectively, of cases with urinary tract and non-urinary tract foci. The adverse influence of inappropriate initial therapy on outcome was more marked in the latter half of the study. PMID- 2267482 TI - Urinary tract infection caused by Corynebacterium group D2: report of 82 cases and review. AB - Corynebacterium group D2 (CGD2) is a slow-growing, urea-splitting, multiantibiotic-resistant microorganism that is frequently isolated from urine samples and that, in certain circumstances, produces infection of the lower urinary tract (acute and chronic cystitis) and the upper urinary tract (pyelonephritis). This paper analyzes (by means of a retrospective and partially prospective clinical protocol) our experience with 82 patients with CGD2 bacteriuria. The infection was symptomatic in 62% of cases, and the clinical diagnoses included acute and chronic cystitis and pyelonephritis with or without bacteremia. Because CGD2 infection of the urinary tract may require specific antimicrobial treatment and because CGD2 is a fastidious microorganism, we recommend prolonged incubation of urine cultures (up to 48-72 hours), especially if the routine culture is negative, when patients are symptomatic, have alkaline urine, or have struvite crystals in the urine sediment. PMID- 2267483 TI - Diarrhea, fever, hypoxia, and rash in a house officer. PMID- 2267484 TI - Typhlitis due to Balantidium coli in captive lowland gorillas. AB - Typhlitis caused by Balantidium coli and requiring surgical resection occurred in three captive lowland gorillas over a 30-month period. Not one of the other gorillas in the colony or their keepers was ill. B. coli is distributed widely geographically and widely among mammals. Asymptomatic commensalism predominates, but invasion of the colonic mucosa can produce diarrhea and dysentery and set the stage for local or systemic spread. PMID- 2267485 TI - Modern chemotherapy for brucellosis in humans. AB - The most effective, least toxic chemotherapy for human brucellosis is still undecided. In vitro, the antibiotics most active against Brucella include the tetracyclines, the aminoglycosides, the aminopenicillins, some cephalosporins, trimethoprim-sulfamethoxazole, erythromycin, rifampin, and some new fluorinated quinolones. Because Brucella species are facultative intracellular parasites, the penetration of drugs into and within phagocytes and phagosomes can be problematic and can best be studied in experimental animals or tissue cultures. In humans, the effectiveness of various regimens of chemotherapy has been compared best in acute bacteremic infections by assessment of the control of symptoms, bacteremia, complications, and relapses. The standard therapy against which all other therapies have been judged is a combination of tetracycline and streptomycin, which is almost universally effective but fails to prevent relapse in 10% of cases. A combination of oral doxycycline and rifampin is convenient and currently popular; it is highly effective, with an average relapse rate of only 8.4%. Trimethoprim-sulfamethoxazole is less effective in controlling bacteremia and other manifestations: in collected series, 5.7% of cases did not respond and 12% relapsed. Drug-resistant Brucella strains are rarely a cause of therapy failure. Localized brucellosis poses special problems, often requiring surgery in addition to prolonged combined chemotherapy. PMID- 2267486 TI - Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review. AB - Malaria associated with complications or a fatal outcome is almost always caused by Plasmodium falciparum. The mortality due to this disease parallels the degree of parasitemia. Successful use of exchange blood transfusion as a therapeutic adjunct for this infection was first reported in 1974, although the efficacy of this procedure has not been established by randomized, controlled trials. The rationale for this form of therapy is based on: (1) rapid reduction in the parasite load by direct removal; (2) decreased risk of severe intravascular hemolysis and its consequences (disseminated intravascular coagulation and renal dysfunction); (3) improved rheology with transfused blood and reduced microcirculatory sludging; and (4) improved oxygen-carrying capacity with transfused erythrocytes. We describe a case of severe falciparum malaria and review the literature describing the use of exchange transfusion for treatment of this infection. PMID- 2267487 TI - Antibiotic-associated hypoprothrombinemia: a review of prospective studies, 1966 1988. AB - Many antimicrobial agents have been associated with hypoprothrombinemia. The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved. The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K. An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT containing regimens. Detailed evaluation of these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia. The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified. We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases. PMID- 2267488 TI - Extrapulmonary pneumocystosis: the first 50 cases. AB - Over the last 35 years, 50 cases of extrapulmonary infection with Pneumocystis carinii have been reported in the literature throughout the world. Use of prophylactic aerosolized pentamidine may have facilitated the relative prevalence of extrapulmonary disease because of its inadequate systemic distribution. An increase in reported cases of infections due to P. carinii has been seen in conjunction with AIDS, but extrapulmonary pneumocystosis represents less than 1% of all cases of infection with P. carinii. Several organs or tissues may be involved, but the most common sites are lymph nodes, spleen, liver, and bone marrow. Extrapulmonary spread of P. carinii infection occurs via both lymphatic and hematogenous routes. While all patients with disseminated forms of this infection die rapidly, survival for patients with AIDS is possible if systemic treatment is provided, if a single extrapulmonary site is involved, and if no concomitant pneumonia is present. Because of the increasing frequency of this condition in patients who do not have pneumonia due to P. carinii, extrapulmonary pneumocystosis should be included among the AIDS-defining criteria. PMID- 2267489 TI - Molecular mechanisms of action of ribavirin. AB - Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad spectrum antiviral agent whose molecular mode of action remains remarkably controversial. This antiviral agent was approved by the U.S. Food and Drug Administration in 1986 for use as an aerosol for infants with serious infections due to respiratory syncytial virus. Ribavirin is and has been under clinical investigation for activity against a variety of viral illnesses, including those due to influenza virus, Lassa fever virus, Hantaan virus, and human immunodeficiency virus (HIV). There has been a great deal of clinical interest in the utilization of ribavirin for treatment of infections due to HIV. It has been reported to slow the development of AIDS in HIV-infected patients. We describe here the major mechanisms of action of this newly licensed antiviral agent. PMID- 2267490 TI - Antifungal and surgical treatment of invasive aspergillosis: review of 2,121 published cases. AB - No controlled trials of therapy for invasive aspergillosis have been done. This review appraises 2,121 cases reported in 497 articles in the literature and analyzes 440 courses of treatment of infection at various body sites in 379 patients. The exclusion of early failures of therapy skews the results toward a favorable outcome. The rate of response to amphotericin B is 55%. Mortality from pulmonary aspergillosis in bone marrow transplant recipients exceeds 94% regardless of therapy, as does that from cerebral aspergillosis in all hosts. Amphotericin B (1 mg/[kg.d]) with flucytosine lowers mortality in neutropenic patients with pulmonary aspergillosis who did not receive a bone marrow transplant; relapse is common. Surgical debridement of aspergillus maxillary sinusitis is usually curative in nonimmunocompromised patients, whereas it increases mortality among neutropenic patients. Valve replacement is essential for aspergillus endocarditis. Both vitrectomy and intravitreal amphotericin B treatment are essential for aspergillus endophthalmitis. Flucytosine is somewhat useful clinically. Itraconazole shows efficacy in the treatment of pulmonary, skeletal, and pericardial aspergillosis. Although liposomal amphotericin B is less toxic than standard preparations of the drug, relevant data are limited. The proposed potentiation of amphotericin B by rifampin is unsupported by clinical data. Despite "conventional" therapy, mortality from invasive aspergillosis remains high; new approaches must be investigated. PMID- 2267491 TI - Pneumococcal infections of the female genital tract. PMID- 2267492 TI - The "toxic strep syndrome": severe group A streptococcal disease in the absence of bacteremia. PMID- 2267493 TI - Severity of meningococcal disease: assessment by factors and scores and implications for patient management. AB - Results from our own and other published series of cases of meningococcal disease were used to study prognostic factors and to compose scores for assessment of severity of disease on admission to the hospital. The difference in risk for fatality was designated the factor fatality difference (FFD); the FFD was determined by subtracting the percent fatality for factor-negative patients from the percent fatality for factor-positive patients. FFD was useful for selection of good indicators of severity of disease. Blood pH of less than 7.35 was the best single factor; low platelet count came next, followed by low blood pressure, cyanosis, ecchymosis, and low blood leukocyte count. New scores were constructed based on multiple regression analyses. Several older and new scores seemed to be comparable. By combining age-adjusted systolic blood pressure (less than 100 mm Hg), cyanosis, ecchymosis, diarrhea before or at admission, cold extremities, absence of nuchal or back rigidity, and rectal temperature of greater than or equal to 40 degrees C, a simple bedside percentage score, the MenOPP bedside clinical score (MOC), was devised. Cross-evaluations on test materials generally confirmed the choice of score. The simplicity of this score made it more clinically suitable than laboratory or mixed laboratory and bedside scores. PMID- 2267494 TI - Native valve endocarditis due to Pseudallescheria boydii in a patient with AIDS: case report and review. AB - A 53-year-old man with AIDS developed mitral valve endocarditis due to infection with the fungus Pseudallescheria boydii. A limited number of cases of prosthetic valve endocarditis caused by this organism have been described. We report a unique case of pseudallescheria infection of a native valve and describe this disease in a patient with AIDS. PMID- 2267495 TI - Nosocomial infections due to Xanthomonas maltophilia (Pseudomonas maltophilia) in patients with cancer. AB - From December 1985 to May 1986, Xanthomonas maltophilia (formerly known as Pseudomonas maltophilia) was isolated at an increased rate at our institution; 52 isolates of X. maltophilia were obtained in cultures of clinical specimens from 38 patients during that time. The records of 35 of these patients form the basis of this study. Twelve (71%) of the 17 infected and nine (50%) of the 18 colonized patients had received or were receiving antimicrobial therapy. Eleven of 17 patients (three of seven with septicemia, three of five with pneumonia, three with urinary tract infection, and two with wound infection) responded to antimicrobial therapy. Microbiologic studies of the potential environmental sources revealed growth of X. maltophilia in two water faucets and in one water sample from the medical intensive care unit. X. maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients, especially those receiving broad-spectrum antimicrobial therapy. PMID- 2267496 TI - The ultrastructure and histology of cholangiocellular carcinomas in English sole (Parophrys vetulus) from Puget Sound, Washington. AB - The ultrastructure and histology of cholangiocellular carcinomas from feral English sole (Parophyrs vetulus) living in polluted waterways of Puget Sound, WA. are described. Electron microscopy confirmed that biliary epithelial cells were the main proliferative cell type composing this variety of neoplasm. The arrangement of these cells varied from well-organized multiple bile duct-like structures to disorganized multilayered sheets of poorly differentiated biliary epithelial cells. A fibrous stroma consisting of multiple layers of collagen fibers and fibroblasts, with macrophages and various blood cell types scattered among these layers occurred between bile duct-like structures or aggregates of biliary epithelial cells. Hepatocytes were not apparent in these neoplasms except within small necrotic regions surrounded by neoplastic biliary epithelial cells. No virus-like particles were observed among the cases examined in this study. PMID- 2267497 TI - Heterotopic gastric mucosa of the small intestine in laboratory beagle dogs. AB - Out of the 365 young laboratory beagle dogs which were used in 17 toxicity bioassays, 15 cases (4.1%) were diagnosed as having congenital heterotopic gastric mucosa of the small intestine. Its incidence in the male dogs (12 cases out of 187) was higher than in the female dogs (3 cases out of 178). Grossly, the lesions were seen as an ulcerous focus of the small intestine, 25 cm to 88 cm proximal to the ileocecal valve. All of the lesions were quite similar histologically and electron microscopically to the normal gastric mucosa, which are composed of the surface mucous cells, chief cells, parietal cells, mucous neck cells and basal granulated cells of the stomach. And consequently, they were considered to be that of a congenital heterotopic tissue in the small intestine. The only morphological characteristic of these lesions different from the regular gastric mucosa was an association with the tubular structure seen in the basal region of these mucosal layers. These cells were considered to be of mucous secreting cell origin because of secreting type III mucous evident from paradoxical concanavalin A or periodic acid Schiff stains. They seemed to be protecting the surrounding intestinal mucosa from gastric acid. PMID- 2267498 TI - Myopathic alterations in extraocular muscle of rats subchronically fed pyridostigmine bromide. AB - To determine if alterations in extraocular muscle morphology occur after subchronic oral administration of pyridostigmine bromide, rats were continuously fed 90 mg/kg in meal and examined at 1, 2, 4, 7, and 15 days. Within the first day, blood acetylcholinesterase activity was reduced by 87% and remained inhibited by 74-91% during the study. Light microscopy demonstrated that by day 1 approximately 3% of the extraocular myofibers were shrunken and invaded by inflammatory cells. The most severe degenerative changes consisting of vacuoles and inflammatory cell infiltration occurred at day 1 with progressively less severe changes at days 2 and 4. At days 7 and 15, 1.3-4.5% of the myofibers still exhibited damage. Ultrastructurally, all presynaptic areas were normal but the postsynaptic areas of affected myofibers at days 1, 2, and 4 showed myofilament and Z-band dissolution, mitochondrial inclusions, subneural fold and T tubule/sarcoplasmic reticulum vacuolization and subneural fold depth reduction. By days 7 and 15, these changes were diminished in some cases and in others alterations appeared similar to day 1. We conclude that subchronic feeding of pyridostigmine bromide induces myopathic rather than neurogenic changes in rat extraocular muscle and that the myopathy is different in these muscles than in the diaphragm from the the same rats. PMID- 2267499 TI - Ultrastructural juxtaglomerular cell changes in normotensive rats treated with quinapril, an inhibitor of angiotensin-converting enzyme. AB - Sequential histologic and ultrastructural changes in juxtaglomerular apparatus (JGA) were defined in male rats treated with quinapril, an inhibitor of angiotensin-converting enzyme (ACE). Doses of 0, 10, 100, and 400 mg/kg were administered daily by gavage for up to 4 weeks. Granular juxtaglomerular (JG) cells were normal or hypogranular on Day 1 at all doses and were hypergranular by Day 7 in rats given 100 and 400 mg/kg relative to age-matched controls. Histologically, JGA hypertrophy was apparent by Day 7 at all doses and was most pronounced by Day 14 in intermediate and deep cortical zones of rats given 100 and 400 mg/kg. Ultrastructurally, hypertrophic JG cells had abundant rough endoplasmic reticulum and free ribosomes, and prominent Golgi complexes associated with numerous cytoplasmic coated vesicles. Dose-dependent increases in numbers of protogranules, altered granules, and cytoplasmic vacuoles occurred in association with decreased size and increased pleomorphism of mature secretory granules. Granule alterations included vesicular to lamellar membranous matrical inclusions, irregular patterns of osmiophilia, matrical vacuolation, and flocculent to coarsely granular matrix of greater density than mature granules. We concluded that JG cell hypertrophy and hyperplasia occurred rapidly in response to subchronic ACE inhibition. Further, ultrastructural changes in JG cells were indicative of stimulated renin synthesis by a regulated pathway, renin secretion by exocytosis and cytoplasmic solubilization of granules, and autophagy of granules as a mechanism whereby JG cells regulate levels of stored renin under conditions of excessive stimulation. PMID- 2267500 TI - Morphometric assessment of thymic size variation in laboratory rabbits. AB - Sections of thymus from New Zealand white rabbits used as controls in 28-day and 91-day percutaneous toxicity studies conducted at different laboratories were morphometrically assessed. Measurements of total thymic area, medullary area, and cortical area were greater for 28-day vs 91-day studies conducted at a given laboratory, but varied from one laboratory to another. Relative thymic measurements (percent medulla, percent cortex, and medulla:cortex ratio) were similar for studies conducted at each laboratory and from one laboratory to another regardless of study duration. A decrease in thymic size occurred between approximately 16 and 25 weeks of age (i.e., 28-day studies vs 91-day studies) due to proportionally equivalent decreases in both the cortical and medullary areas. The consistency of the relative measurements can be used to assist in distinguishing changes in thymic size due to aging from changes in size due to stress or toxicity which would be expected to differentially affect the cortical and medullary areas. Appreciation of the normal variation in thymic size is needed when evaluating results of toxicity testing in rabbits. Data are provided as to the degree of normal variation of rabbit thymic size expected within and across percutaneous toxicity studies, with considerations for interpreting such data. PMID- 2267501 TI - Tissue reaction to an implantable identification device in mice. AB - Long-term toxicity and carcinogenicity studies require positive identification of animals. Due to the unreliability of traditional methods, it was necessary to investigate more dependable identification methods that can be read directly or by electronic means. A two-year study to determine the stability of and tissue reaction to a microchip glass-sealed device implanted in subcutaneous tissue of mice was conducted. Seventy B6C3F1 mice of each sex were anesthetized and implanted with the microchip. The devices were read by an electronic detector and palpated at periodic intervals. Ten mice of each sex were necropsied at 3 months and at 15 months with the remaining animals necropsied at 24 months. Of the 140 devices implanted, 3 were lost and 4 failed during the 24-month study. Devices were palpable and appeared to be fixed at one location with no obvious swelling due to inflammation or palpable masses around the implants for 24 months. At the 3, 15, and 24 month necropsies, implants were encapsulated by connective tissue. Light microscopic evaluation indicated that the capsule around the implants was thin and composed of fibrocytes and mature collagen fibers, with minimal to mild inflammation and occasional granulomatous reaction. Neoplastic changes were not observed in the tissue around the glass-sealed devices with polypropylene cap for up to 24 months. PMID- 2267502 TI - Proliferative exocrine pancreatic lesions in aged Wistar rats. PMID- 2267503 TI - Spontaneous primary astrocytoma in the spinal cord of a mouse and a rat. AB - A spontaneous astrocytoma was observed as an incidental finding in the thoracic spinal cord of a control Charles Rivers CD-1 female mouse from a 2 yr oncogenicity study. An astrocytoma was also observed in the lumbar spinal cord of a Charles Rivers Sprague-Dawley control, female rat from a 2 yr oncogenicity study. The mouse was clinically normal and was sacrificed at the end of the 2 yr study. The rat was killed at 512 days of age because of posterior paralysis. PMID- 2267504 TI - Did a patient get AIDS from a clinician? PMID- 2267505 TI - For HIV patients survival increases the risk of lymphoma. PMID- 2267506 TI - When the "patient" is a whole community. PMID- 2267507 TI - Patient's advocate. "You can go home again". PMID- 2267508 TI - Why aren't we protecting our children? PMID- 2267509 TI - Get your patient off on the right foot. PMID- 2267510 TI - One way up. Build on passion. PMID- 2267511 TI - Hypertension: the nurse's role. PMID- 2267512 TI - Can you solve this assessment puzzle? PMID- 2267513 TI - A promising new use for UV light. PMID- 2267514 TI - Legally speaking. Careful charting--your best defense. PMID- 2267515 TI - Sugar: empty calories, or worse? PMID- 2267516 TI - Article on Meniere's sheds light on little-known disease. PMID- 2267517 TI - This program breathes new life into inservices. PMID- 2267518 TI - Patient's advocate. Why this baby got special treatment. PMID- 2267519 TI - Most breast lumps aren't cancer! PMID- 2267520 TI - Nursing the mind. Easing life for the Alzheimer's patient. PMID- 2267521 TI - Helping patients give the gift of life. PMID- 2267523 TI - RN pins: the tradition continues. PMID- 2267522 TI - A different kind of recovery. PMID- 2267524 TI - What's wrong with this patient? PMID- 2267525 TI - Hypertension: the role of diet and lifestyle. PMID- 2267526 TI - Legally speaking. Keep quiet or speak up? Issues in patient confidentiality. PMID- 2267527 TI - Home care. Infection control takes top priority. PMID- 2267528 TI - Incest survivors may "forget" they've been abused. PMID- 2267529 TI - Can pentamidine prevent pneumonia in HIV patients? PMID- 2267530 TI - Ben's death. PMID- 2267531 TI - Sometimes a nurse needs to be "just" a wife. PMID- 2267532 TI - For smoother shift changes, try walking rounds. PMID- 2267533 TI - Patient's advocate. exporting health--and hope. PMID- 2267534 TI - Nursing the mind. Managing mood disorders. PMID- 2267535 TI - A new option for cystectomy patients. PMID- 2267536 TI - Patient teaching for X-ray and other diagnostics. Intravenous pyelogram. PMID- 2267537 TI - Brain tumor. Frightening diagnosis, nursing challenge. PMID- 2267538 TI - Seeding the tumor. PMID- 2267539 TI - When you give phenytoin i.v. PMID- 2267540 TI - CF. Not just a pediatric problem anymore. PMID- 2267542 TI - Filling gaps. PMID- 2267541 TI - Legally speaking. The double risk of delegating. PMID- 2267543 TI - Nutrition support. Your elderly patient needs special attention. PMID- 2267544 TI - Other hints for treating xerostomia. PMID- 2267545 TI - Laughter: the best medicine. PMID- 2267546 TI - Health care in transition. PMID- 2267547 TI - Nurse helps students make informed choices about smoking. PMID- 2267548 TI - Smoking program focuses on smoking awareness. PMID- 2267550 TI - Reflections on the health system. PMID- 2267549 TI - CPR certification: who is responsible? PMID- 2267552 TI - [Content of metals in vegetables from various regions of poland in the years 1986 1988. II. Content of zinc and copper]. AB - The content of zinc and copper was determined in various sorts of vegetables grown in hothouses or on soil. This content was determined also in the soil where these vegetables were grown. The samples of these vegetables were taken directly from the producers in 18 provinces of Poland from the areas not contaminated by industrial plants and traffic. The content of Cu and Zn was determined after dry mineralization of samples at 400 degrees C by ASA method in adequately diluted aqueous solutions of the mineralized substances. In all 2522 samples of vegetables grown in hothouses or on soil and 635 samples of soil were studied. The zinc level in most samples was lower than the permissible level 10 mg/kg. The highest amounts of zinc were found in red beets, and in the leaves of parsley grown in hothouses and on soil. The copper content in these samples was much below the permissible level of 4 mg/kg. The mean values of copper and zinc in soil samples were higher than the values accepted as present most frequently in soil in non-contaminated regions of Poland, that is 15 and 90 mg/kg respectively. PMID- 2267551 TI - [Content of metals in vegetables from various regions of Poland in the years 1986 1988. I. Content of lead, cadmium and mercury]. AB - The content of lead, cadmium and mercury was determined in various sorts of Polish vegetables grown on soil or in hothouses in the years 1986-1988 using for the determination of Pb and Cd the extraction flame ASA method after dry mineralization at about 400 degrees C and for Hg the flameless ASA method after wet mineralization. In 1988 soil investigations were conducted parallelly in the areas where these vegetables had been grown. Vegetable samples were taken directly from the producers in 18 provinces, from areas not contaminated with these metals by industrial plants and traffic. About 2.5 thousand vegetable samples and about 650 soil samples were investigated. A considerable part of the vegetables, especially those whose roots are consumed, contained excessive amounts of lead--over 0.3 mg/kg (e.g. over 20% of samples of parsley leaves) and cadmium--over 0.3 mg/kg (nearly 40% of carrots samples, and about 30% of beets, lettuce grown on soil or in hothouses, and parsley roots, about 20% of samples of parsley leaves grown on soil). The levels of mercury were usually of the order of thousandths mg/kg. The mean values of these metals in soil were frequently much higher than the values regarded as most frequent in the soils of not contaminated regions of Poland. PMID- 2267553 TI - [Soil contamination from industrial and community waste in the Cracow area]. AB - Problems are discussed connected with the contamination of soil with industrial and community waste in the period 1980-1987. In the Cracow area 82 million tons of waste was accumulated on dumping grounds, waste heaps and in sedimentation ponds for sewage which cover already 1.2% of the area. Among this waste 34% is produced by steel plants, 16% is mineral waste, 9% waste is produced by power plants, and 8% by chemical plants. Particular risk is connected with toxic waste produced mainly by the Lenin Steel Plant, Alwernia Chemical Plant, and Bonarka Cracow Inorganic Industry Plant. In the last 4 years an increase was observed in the amount of processed waste and the amount of dumped waste has decreased by 7.6% in the years 1984-1987. Nevertheless, the problem of processing or neutralization of toxic waste remains to be solved. PMID- 2267554 TI - [Hygienic conditions and the quality of nutrition in workers' canteens in the province of Ciechanow]. AB - In 1987 the hygienic condition was analysed of 28 workers' canteens in the Province of Ciechanow considering also the quality of lunches or the se called regenerative-fortifying meals. The inspection showed that the hygienic condition of 14 canteens (40%) was unsatisfactory. The microbiological cleanliness of the equipment was questioned most frequently in these canteens in which the hygienic condition was below standard. In 28 canteens controlled the nutrition was incorrect in view of deviations from the accepted standard content of protein, fats and carbohydrates as well as energy. The food rations expressed in 12 groups of products in 21 canteens differed from the recommended values for partial nutrition. It was found also that the occupational qualifications and the level of knowledge on rational nutrition of the staff and personnel in the canteens were unsatisfactory. PMID- 2267555 TI - [Nutritional value of daily food rations reproduced in several regions of the country. Part II. Nutritional value of protein]. AB - The amount and quality of protein were determined in daily food rations of workers, including blue collar and white collar ones, which were reproduced in the laboratory on the basis of the data provided by the Central Statistical Bureau concerning the mean annual food consumption in 1986 (studies on household budgets). The amount of protein in the daily food ration of blue collar workers was higher (76 g) than in the families of white collar workers (68 g). The amount of energy provided by protein (12%) and the degree of coverage of the requirements for protein (mean 92%) were similar in both rations. The nutritional value of protein expressed as the NPU coefficient of protein utilization was relatively low in both rations (mean 66%). A comparison of these food rations in the years 1973, 1980, 1981 and 1986 showed that in 1980 the rations had the highest protein content (mean 93 g daily)--the highest proportion of protein derived energy (mean 14%) and the highest proportion of protein requirement coverage (mean 120%). The nutritional value of protein (NPU, mean value 71%) was similar to that in 1973 and 1981. As compared to the preceding years the food rations in 1986 showed the lowest coverage of protein requirements and lower nutritional value as expressed with the NPUop index. A high correlation was found between the amino acid composition of dietary protein obtained by chemical analysis and those calculated from the Tables of Composition and Nutritional Value of Food Products. PMID- 2267556 TI - [Nitrates and nitrites and the utilization of beta-carotene. I. The effect of different amounts of dietary nitrates and nitrites on the utilization of beta carotene in rats]. AB - The subject of the study was demonstration whether and in what extent different amounts of nitrates and nitrites in the diet affect the utilization of beta carotene by rat organism. The level of vitamin A in the liver was accepted as an indicator of this utilization in accordance with the method of combined balance studies and liver test; additionally the plasma vitamin A level was determined. Two biological experiments lasting 30 days were carried out on male Wistar rats standardized with respect to hepatic vitamin A content. The animals were given orally 30 mcg daily an oil solution of beta-carotene and diets with varying amounts of potassium nitrate (0.5; 1.0; 2.0; 4.0; 6.0%) and sodium nitrite (0.05; 0.1; 0.5; 1.0%). Nitrates and nitrites in the diets reduced the utilization of beta-carotene in a dose-dependent way. The nitrate reduced the utilization of the provitamins by from about 50% to over 60%, and the nitrite reduced it by from over 60% to about 80%. The studied compounds exerted also a negative effect on the consumption of diet and weight gain. PMID- 2267557 TI - [The effect of technological intervention on histamine content in fish preservation]. AB - The effect was studied of preliminary and proper processing (sterilization) on histamine content in 4 types of canned fish: mackerel in sauce, mackerel in tomato sauce, hake fillets in oil, and Szczecin fish with paprika. Histamine level was determined also in the meat of herring during production of pickled herring and smoked herring. The colorimetric method described by Hardy and Smith was used for histamine determination. In all analysed products at all stages of processing, including sterilization, no effect was observed of the correctly conducted technological processes on histamine level rise. The processes of fish smoking (in heat) and pickling baths of fish increased slightly the content of histamine in the finished product. The mean histamine content in pickled fish was 7.38 mg/100 g, and in smoked herring the maximal histamine value was 3.5 mg/100 g. PMID- 2267558 TI - [Presence of nitrates and nitrites in baker's products and in certain other flour products]. AB - The results of the study demonstrated that the content of nitrates and nitrites in various baker's products varied from 0.96 (in wheat rolls and baguettes) to 44.07 mg KO3/kg in pumpernickel bread. In wholemeal bread, village bread, tourist bread, rye brown bread and Graham bread the content of these compounds was from 1.46 to 27.10 mg KNO3/kg. The mean content of nitrites in these bread sorts was 1.76 mg NaNo2/kg, range 0.10-4.40 mg NaNo2/kg. In white wheat flours (Wroclaw flour, cake flour and Poznan flour) the content of nitrates ranged from 1.10 to 19.08 mg KNO3/kg, and in the dishes produced from them in household was from 0.50 to 16.33 mg KNO3/kg. The content of nitrites in these flours was in the range from 0.00 to 4.16 mg NaNo2/kg, and in the products prepared from them it was from 0.00 to 1.60 mg NaNO2/kg. Eleven types were tested also of popular biscuits, wafers, gingerbread and hard cakes in which the content of nitrates was from 3.66 to 17.72 mg/kg, and that of nitrites was from 0.00 to 8.80 mg NaNo2/kg. Considering the average consumption of these products per one person in the seashore region and the mean values of nitrates and nitrites it was calculated that they provided daily about 3.9 mg KNO3 and 0.4 NaNo2, that is about 1.8% of nitrates and 7.7% of nitrites consumed by adults in daily food ration. PMID- 2267559 TI - [Effect of preincubation time and concentration of selective media on the effectiveness of salmonella organism isolation from frozen meat homogenates]. AB - Double concentrated RV and SC media were used for selective multiplication of frozen meat homogenates preincubated in buffered peptone water during 6 and 20 hours. It was found that cultures of 2 ml of homogenate preincubated during 6 hours in 10 ml of twofold concentrated RV medium, and selective multiplication during 20 hours made possible obtaining of a greater number of Salmonella isolates as compared to samples preincubated during 20 hours and transferred in volumes of 0.1 ml into 10 ml of normal concentration medium. On the other hand, the growth of 1 ml of a culture preincubated during 6 hours transferred into 10 ml of twofold concentrated SC medium yielded a similar number of salmonella isolates as in the case of samples preincubated during 24 h and transferred in 1 ml volumes into 10 ml of the SC medium without concentration change. PMID- 2267560 TI - [Health evaluation of antioxidant exposure in the food industry]. AB - The assessment of the present health effects of the antioxidants used in food industry was based on the reports of the Joint FAO/WHO Expert Committee on Food Additives. The results are included of toxicological investigations which were considered establishing the opinion of the Expert Committee, and the ADI values for these substances are quoted. A list of antioxidants and their synergists prepared by the Expert Committee is included, together with the list of those accepted by the Polish regulations. PMID- 2267561 TI - [Aluminum--occurrence and characteristics of toxicity]. AB - On the basis of a literature survey the problems are discussed related to the presence of aluminum in the natural environment and its effects on the human organism. Data are presented on the content of the element in food and potential sources. PMID- 2267562 TI - [The role of Doppler echography in the evaluation of systolic and/or diastolic dysfunction of the left ventricle]. AB - The doppler-echocardiographic assessment of left ventricular systolic and diastolic dysfunction involves numerous indices. Preload is evaluated by measurement of the end-diastolic left ventricular diameter and sometimes by the rapid filling E wave on doppler recordings. The best index of of afterload is the end-systolic stress. Most indices of contractility are load-dependent, including percentage of fibre shortening, FCV, FCVc, EF. This leads to the construction of end-systolic regression slopes by varying the load to determine the myocardial contractile value. In the future, automated analysis of doppler curves will be used to determine the aortic flow maximal acceleration. The diastolic function is easily evaluated through the transmitral flow, but its interpretation must take into account the patient's age, heart rate and filling state. Two aspects are regarded as pathological: the filling disorder aspect with E/A under 1, and the hypernormal assay described by Appleton. In doppler-echocardiographic studies as well as in haemodynamic studies all these indices are interrelated, which shows the complexity of cardiac physiology and the interdependence of its factors. PMID- 2267563 TI - [Usefulness of exercise tests in the evaluation of the effects of treatment in chronic cardiac insufficiency]. AB - Before it reaches the decompensation stage, heart failure is characterized by symptoms which occur only during exercise. It is therefore rational to believe that the effectiveness of treatments of heart failure should be evaluated by the improvement they produce in tolerance to stress. This tolerance can be evaluated by exercise tests which may take different forms. The most common is a progressive load test on bicycle ergometer or treadmill. Among the indices used to assess tolerance to stress, the total duration of the exercise test until symptoms develop is a variable subject to fluctuations which may be independent of the patient's cardiovascular state. Measurement of oxygen consumption at peak exercise level is usually preferred, being unrelated to the nature of the stress and much more reproducible and sensitive to changes. Among the pharmacological treatments of heart failure, only chronic vasodilator therapy, notably with angiotensin-converting enzyme inhibitors, has proved constantly effective on the various ergometric indices. In the literature, the effects of digitalis compounds, dihydralazine and alpha-blockers are inconstant. Among the new treatments of heart failure, phosphodiesterase inhibitors may improve tolerance to stress, as does Corwin which may prolong the total duration of exercise. Its effect on oxygen consumption has not yet been evaluated. Performance at exercise is almost never improved by acute treatment with any pharmacological agent, and the same remarks applies to short-term heart transplantation. The reason for this is that heart failure is associated with a physical deconditioning syndrome due to abnormalities of the arterial dilatation capacity in skeletal muscles, and with muscular metabolic abnormalities due to a defective oxygen utilization by these muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267564 TI - [The treatment of chronic left ventricular insufficiency]. AB - Left ventricular failure is caused by a variety of myocardial diseases and its symptoms results from adjustments attempted by the left ventricle and the circulatory system to cope with the initial myocardial pathology. Treatment of heart failure has various objectives, depending on whether one tries to correct the initial myocardial disease, or its consequences on the myocardium, or its repercussions on blood circulation, or, more simply, to alleviate the symptoms experienced by the patient. The ideal treatment of heart failure would include a drug acting on its cause, another drug to restore a degree of contraction and relaxation adjusted to the amount of load, a third drug bringing back to normal a perturbed peripheral circulation and a fourth drug to relieve the symptoms due to sodium retention. Such a treatment does not exist, and the management of chronic left ventricular failure can only be composite. Should it be prescribed from the start? This, increasingly, is the current trend. PMID- 2267566 TI - [Chronic left ventricular insufficiency]. PMID- 2267565 TI - [Converting enzyme inhibitors and cardiac insufficiency: current findings and perspectives]. AB - Angiotensin-converting enzyme inhibitors are mixed vasodilators with a prolonged sustained effect in chronic heart failure. They also act on the reactivity of peripheral circulation, on ventricular remodelling after myocardial infarction, on myocardial hypertrophy in arterial hypertension and on ventricular hyperexcitability. They alleviate the symptoms of symptomatic heart failure, and they constitute the only treatment that has been able to improve the survival of patients with the most severe heart failure. Several studies are in progress to determine whether these drugs should be used as first-line therapy. PMID- 2267567 TI - [Effect of catecholamines on the smooth muscles of the esophageal groove of calves]. AB - The effect of noradrenaline and adrenaline on isolated smooth muscle from the reticular groove of calves was studied. Both catecholamines caused a concentration-dependent (1.1.10(-6) mol/l) contraction of the transversal muscle strips from the floor of the reticular groove. This excitatory effect was antagonized by prazosin (10(-7)) mol/l), and by high concentrations of yohimbine (10(-6) mol/l) and atropine (10(-5)) mol/l). Tetrodotoxin (3.10(-6) mol/l), an inhibitor of nerve conduction, did not change the contraction induced by catecholamines (55.10(-6)) mol/l). Catecholamines did not produce a contraction of the longitudinal muscle from the lips of the reticular groove. The beta adrenergic agonist isoprenaline (55.10(-6) mol/l) even elicited a reduction of acetylcholine (55.10(-6)) mol/l) induced contraction of both the transversal and the longitudinal muscle from the reticular groove. The relaxing effect of isoprenaline was antagonized by propranolol (55.10(-6)) mol/l). According to these results the excitatory effect of catecholamines on the smooth muscle cells occurs through alpha-adrenergic receptors, whereas the relaxing effect is mediated by beta-adrenergic receptors of the muscle cell. The excitatory effect of catecholamines on the transversal muscle appears to be predominant. Atropine appears to be an unspecific blocking agent of alpha-adrenergic receptors. PMID- 2267569 TI - Comparison of bronchoalveolar lavage and respiratory secretion cytology in horses with clinically diagnosed chronic pulmonary disease. AB - Thirty-nine horses and 3 ponies underwent a thorough respiratory examination and were grouped as follows: healthy (4 horses and 1 pony); mild chronic pulmonary disease (CPD 11 horses); moderate CPD (16 horses and 1 pony); and severe CPD (8 horses and 1 pony). Bronchoalveolar lavage (BAL) fluid collected from all animals and respiratory secretions (RS) obtained from 39 of these animals were evaluated cytologically and the results were compared. It was concluded that cytological examination of either BAL fluid or RS was useful in diagnosing various equine pulmonary diseases. The only advantage that BAL offered over RS sampling was in cases in which there was no RS available in the trachea. In addition, the severity of the CPD did not always correlate with either RS or BAL cytology. PMID- 2267568 TI - Pharmacodynamic evaluation of the peripheral pain inhibition by carprofen and flunixin in the horse. AB - Carprofen, flunixin meglumine and placebo in the form of a physiological solution of sodium chloride were tested in an open randomised cross-over trial for analgesic efficacy in horses with two external skin-stimulation systems. Both systems, the withers model and the "heating element" model, were compared in order to find an optimal way to measure pain perception after stimulating the skin with high temperature. No analgesic effect of flunixin or carprofen could be demonstrated when using the withers model. In the "heating element" model, a 1.1 mg/kg i.v. dose of flunixin meglumine failed to inhibit the peripheral pain, while it could be shown that a 0.7 mg/kg i.v. dose of carprofen inhibited the peripheral perception of pain in horses for approximately 24 hours after the drug injection. To induce an analgesic effect with carprofen, its plasma concentration had to be at least 1.5 micrograms/ml. PMID- 2267570 TI - [The uterine motility in cattle during late pregnancy, labor and puerperium. II. Drug modification]. AB - The uterine effects of oxytocin, the prostaglandins dinoprost and cloprostenol as well as clenbuterol, ergometrin, xylazine and Utrorale were investigated in 8 cows during late pregnancy, parturition and early puerperium (until 4th day p. p.). Uterine motility was measured by means of pressure microsensors and electrodes which were surgically implanted 3 to 4 weeks before parturition. Hysterograms were characterized by means of pressure amplitude, frequency and duration of uterine contractions and also by electromyography. Oxytocin (2-5 IE) given intravenously always provoked strong uterine contractions until the 4th day p.p. From the prostaglandins examined during early puerperium only dinoprost (15 mg i.v.) produced uterotonic effects, while the synthetic analogue cloprostenol (0.25 mg i.v.) had a weak stimulatory activity only on day 1 p.p. Both prostaglandins were ineffective when injected intramuscularly. Clenbuterol (0.3 mg i.v.) a beta 2-mimetic compound effectively induced long lasting tocolysis during parturition, which could be abolished by oxytocin. Xylazine (10 mg i.v.) was able to significantly increase uterine motility during late gestation. Following intravenous administration of ergometrin (1 and 10 mg), bunitrolol (1 16 mg) and Utrorale (0.1-4 ml) including its compounds oleum sabinae, oleum terebinthinae, balsamum copaivale and Styrax no uterokinetic activity was recorded at any time. PMID- 2267571 TI - [What is your diagnosis? Which treatment do you suggest?]. PMID- 2267572 TI - Agrobacterium in plant disease, biological disease control and plant genetic engineering. AB - Plant pathogenic strains of Agrobacterium cause crown gall and hairy-root diseases. The abnormal cell proliferation of diseased tissues results from elevated plant hormonal levels within them. These levels are consequent upon the transfer of DNA portions (T-DNA) from Agrobacterium plasmids to host nuclei where they are integrated and where genes for hormone synthesis, borne on the T-DNA, are expressed in transformed host cells. This process has been exploited in plant genetic engineering by producing Agrobacterium mutants with deleterious genes removed from T-DNA, and with selected beneficial genes inserted in their place. Such mutants are able to infect and transform plants so that the beneficial genes are transferred to, and expressed in, the host plants, endowing them with desirable characteristics, including insect and disease resistance and herbicide tolerance. Biological control of Agrobacterium disease has been achieved using non-pathogenic Agrobacterium strains which produce an antibiotic specifically inhibitory to Agrobacterium pathogens. Use of one of these biocontrol strains is the first instance of a genetically engineered micro-organism being released commercially. PMID- 2267573 TI - Peptide vaccines for viral diseases. AB - The technique of vaccination developed over 200 years ago has played a major role in the control and eradication of viral diseases both in man and in animals. Most current viral vaccines are either live attenuated (weakened) or inactivated (killed) products which, despite being highly successful, can have certain limitations regarding their safety and efficacy. Furthermore, there are a number of important viral diseases for which it has not been possible to develop vaccines by conventional means. Armed with an increased knowledge of the molecular structure of viruses and the requirements for a protective immune response, scientists have recently turned their attention to novel vaccine approaches. One such approach has been to define sites on a virus particle responsible for eliciting protective immunity and to use chemically or biologically synthesized short chains of amino acids (peptides) representing these sites as potential vaccines. This review looks briefly at the historical background to the development of peptide vaccines for viral diseases. It then considers how appropriate peptides may be identified and the problems associated with their optimal-delivery to the immune system. Finally, it looks at the advantages of and future prospects for such technology. PMID- 2267574 TI - New nursing diagnoses accepted for clinical testing. PMID- 2267576 TI - Environmental trends impact nursing's future. PMID- 2267575 TI - AIDS education and the school nurse. PMID- 2267578 TI - [Diagnosis of breast cancer in outpatient clinics]. PMID- 2267577 TI - [Endomyocardial biopsy in complicated congenital heart defects]. AB - Endomyocardial biopsy followed by myocardium examination helps detect the changes characteristic of bacterial endocarditis at different stages. This allows rational treatment conducive to a favorable course of the postoperative period. PMID- 2267579 TI - [Immunological diagnostic methods in clinical practice]. PMID- 2267580 TI - [M-mode echocardiography: calculation of the parameters using a programmed microcomputer]. PMID- 2267581 TI - [Treatment of pseudotuberculosis with diaminodiphenylsulfone]. PMID- 2267582 TI - [Emergency health care in disasters]. PMID- 2267583 TI - [Biochemical aspects of chronic pancreatitis]. PMID- 2267584 TI - [Improving moral standards]. PMID- 2267585 TI - [Disorders of hemostasis in atherosclerosis in middle-aged and aged patients]. PMID- 2267586 TI - [Formation of the motivation for professional work of the physician during training of 1st-year students]. PMID- 2267587 TI - [Planning of medical examinations and health-improving measures based on the findings of automated screening]. PMID- 2267588 TI - [Basic approaches to prevention of drug addiction]. PMID- 2267589 TI - [Comparative effectiveness of propranolol and acebutolol in arterial hypertension]. PMID- 2267590 TI - [Echocardiography and transesophageal electrocardiostimulation in the diagnosis of early stages of alcoholic lesions of the heart]. PMID- 2267591 TI - [Clinical picture and diagnosis of Gilbert's syndrome]. PMID- 2267592 TI - [Characteristics of transurethral resection of the bladder in cancer]. PMID- 2267593 TI - [Reconstructive-reducing surgery in cancer of the left colon]. PMID- 2267594 TI - [Effects of mildronate (quaterin) on hemodynamics in spontaneous and artificial heart rhythm in patients with ischemic heart disease]. AB - Central hemodynamic parameters under the effect of mildronate were examined in 62 patients suffering from coronary heart disease, 35 of these with acute myocardial infarction complicated by acute left-ventricular insufficiency and 20 with atherosclerotic cardiosclerosis with chronic cardiac insufficiency. The drug effect was assessed in two groups of patients after a single intravenous injection of 0.5-3 g. In group 1 (n = 53) mildronate effect on central hemodynamic parameters was assessed in spontaneous cardiac rhythm. Variously directed statistically unreliable hemodynamic shifts were revealed, related to heart rhythm changes. In group 2 (n = 9) the drug effect on heart rhythm was eliminated with the use of two-chamber electrocardiostimulation, and various hemodynamic regimens with hypo-, eu-, and hyperkinetic circulation types were artificially created by changing the A-V interval. Mildronate had no effect on the hemodynamics during two-chamber electrocardiostimulation. PMID- 2267595 TI - [Characteristics of hepatic echinococcosis in a Siberian focus]. PMID- 2267597 TI - [Functional dumping syndrome]. PMID- 2267596 TI - [Clinico-immunological aspects of intestinal Klebsiella infection]. PMID- 2267599 TI - [Effectiveness of cryogenic and cryo-ultrasonic methods in the treatment of pathological processes of the cervix uteri]. PMID- 2267598 TI - [Immunocorrective effects of detoxication therapy in suppurative-infectious diseases of organs of the abdominal cavity]. PMID- 2267600 TI - [Prevention of wound infection in open injuries of the hand]. PMID- 2267601 TI - Complications of lateral C1-2 puncture myelography. AB - This study reviewed the technical complication of 112 cases of lateral C1-2 puncture myelography for cervical spinal cord disorders. Spinal cord puncture and contrast injection, puncture between the occiput and C1, and blood vessel puncture were the main complications. These principally depended on the positioning of the patient's neck (hyperextension) and misdirection of the x-ray beam. For preventing major arterial puncture, the authors also reviewed 164 vertebral angiograms and determined the pathway of the vertebral arteries and the incidence of anomaly. PMID- 2267602 TI - Clinical value of magnetic resonance imaging for cervical myelopathy. AB - The magnetic resonance imaging (MRI) findings in 115 cases of cervical myelopathy, 121 cases of cervical radiculopathy, and 64 cases of neck pain with no neurologic deficit were prospectively studied to investigate the clinical value of MRI for cervical myelopathy. The MRI findings in the T1-weighted sagittal projection were classified into four groups according to the degree of the compressed deformities of the cervical cord. The degree of compression of the cervical cord on MRI findings showed a significant correlation with the severity of myelopathy, the anteroposterior diameter of the spinal column, and the degree of compression of the dural tube in the myelograms (P less than 0.01). Fifty-one patients of cervical myelopathy had undergone both preoperative and postoperative MRI. Of these, the spinal canal of 47 patients that was well decompressed was recognized according to plain computed tomography (CT). However, 24 (51%) of these 47 patients showed on MRI a deformity in the spinal cord amounting to cord atrophy. The correlation between the clinical function of the spinal cord and the recovery of the cord deformity on MRI at the operative levels was accurately investigated in 34 patients who had no cord deformities in the adjacent intervertebral levels. Twenty patients with cord atrophy had slightly poor clinical results, although no significant difference was found between these 20 and 14 patients with recovery in the cord deformities. From these results, it was evident that T1-weighted MRI is useful in the accurate diagnosis of compression myelopathy, in accurately deciding the level of the disease focus, and in the accurate assessment of the surgical results. PMID- 2267603 TI - Motion analysis of the cervical spine in athetoid cerebral palsy. Extension flexion motion. AB - Frequently instability and premature onset of spondylosis of the cervical spine are found in athetoid cerebral palsy (CP) patients. These structural abnormalities appear to be related to athetoid motion of the neck in CP. Through motion analysis, the authors aimed to clarify the abnormalities of cervical motion that could precipitate structural abnormalities. The gross characteristic feature of cervical motion in athetoid CP is "whip movement." Both velocity and acceleration during extension-flexion motion were greater than in normal subjects, especially at the upper cervical levels. Also, a sudden increase in velocity and acceleration occurred during rapid motions at certain levels, followed by a larger range of motion of the cervical spine. Such kinematic abnormalities were thought to generate a greater shearing force and bending moment exerted on the corresponding cervical articulations-discs and facets. Olisthetic instability often accompanied disc degeneration at the upper cervical levels. A large range of extension--flexion motion of the cervical spine, analogous to a cantilever, caused a repeated bending moment of extraordinary magnitude and was regarded as a precipitative factor for disc degeneration and osteophytosis common at the middle and lower levels of the disc. PMID- 2267604 TI - A histopathologic study of spinal cord ischemia using an isohistogenic rat upper half-body transplantation model. AB - To study the histopathologic changes of spinal cords exposed to long-duration complete ischemia, the authors developed an upper-half-body transplantation model of inbred rat. In this model, an infant Lewis rat is transplanted to the inguinal region of another adult Lewis rat using microsurgical vascular anastomosis. Even when 2-week-old donor rats were exposed to complete ischemia for 90 minutes, functions of the spinal cord were comparatively preserved. In histopathologic observations, degeneration proportional to complete ischemia duration was noted. In the 60-minute ischemia group of 2-week-old donor rats, however, no substantial differences from normal spinal cord were observed. Under conditions of equal ischemia duration, it appeared the younger animal had the greater ischemic tolerance. PMID- 2267605 TI - Dynamic analysis of the Harrington system using a spinal simulator. AB - The authors constructed a spinal simulator for the thoracolumbar spine with mechanical properties similar to those of cadaver specimens, and studied the effectiveness of the Harrington system in unstable fractures of the thoracolumbar spine. Distraction and compression rods were applied under various conditions. External bending moment was applied to the model to measure the internal bending moment on the vertebral body and ligaments. Optimal spinal stability was obtained when the distraction system was combined with the compression system with hooks at laminas three levels above and below the fracture. PMID- 2267606 TI - Identification of alpha-motor nerve fiber potentials in lumbar epidural space and its clinical significance. AB - The alpha-efferent component of spinal root potentials (SRPs) was recorded in the lumbar epidural space stimulating the tibial and peroneal nerves for clinical diagnosis and clinical treatment. Five normal volunteers and 15 clinical cases with lumbar disc herniation (LDH) were examined. The SRP by the tibial nerve stimulation in the normal control group consisted of two kinds of potentials with different latency. Simultaneous electromyogram (EMG) recording from the stimulated muscles indicated that the shortest latency potential (first potential) was the ascending volley, including orthodromic afferent and antidromic alpha-efferent volleys; and that the long latency potential (second potential) was the descending volley of reflexively evoked alpha-efferents by the Group Ia afferents. The component of alpha-efferent fiber potential was recorded in the following two methods by changing the intensity of stimulation: 1) identifying alpha-efferent components in the first potential and 2) recording the second potential. Conduction blockage of spinal roots in 15 clinical cases was demonstrated as abnormal positivity and prolonged duration of the potentials. New methods were introduced to estimate two parameters quantitatively. The present study showed either of these signs in all patients tested. The examination was helpful to determine the level(s) of lumbar motor radiculopathies, and the extent of pathologic neuropathy. PMID- 2267607 TI - The role of the iliolumbar ligament in the lumbosacral junction. AB - The biomechanical function of the iliolumbar ligament in the human lumbosacral junction was investigated by analyzing the three-dimensional movements of the whole lumbar and lumbo-sacral-ilium specimens. The experiment was repeated in the following three conditions: 1) intact iliolumbar ligament, 2) right iliolumbar ligament transected, and 3) bilateral iliolumbar ligaments transected. The representative values of the increased motions, compared with intact, after transection of the bilateral iliolumbar ligaments were 1.7 degrees (23%) in flexion, 1.1 degrees (20%) in extension, 0.3 degrees (18%) in axial rotation, and 1.2 degrees (29%) in lateral bending. The most restricted motion governed by the iliolumbar ligament in the lumbosacral junction was lateral bending. The bilateral iliolumbar ligament specimen could restrict flexion and extension of the lumbosacral junction, but the unilateral iliolumbar ligament preparation alone could not restrict these motions. The iliolumbar ligament also had the function of restricting the rotational movement of the lumbosacral junction. PMID- 2267608 TI - Biomechanical evaluation of lumbar spinal stability after graded facetectomies. AB - In an in vitro experiment using fresh human lumbar functional spinal units, the effects of the division of the posterior ligaments (consisting of the supraspinous/interspinous ligaments) and graded facetectomies were investigated. The graded facetectomies consisted of unilateral and bilateral medial facetectomies, and unilateral and bilateral total facetectomies. Six kinds of moments were applied and ranges of motion (ROM) and neutral zones (NZ) were determined three-dimensionally by stereophotogrammetric methods. Range of motion was not affected by the division of the supraspinous/interspinous ligaments for all load modes. In flexion, ROM increased slightly after unilateral medial facetectomy. In right axial rotation, ROM increased after left unilateral total facetectomy. Range of motion was not affected, even by bilateral total facetectomies, in extension and lateral bendings. This study suggested that medial facetectomy does not affect lumbar spinal stability, and conversely, total facetectomy, even created unilaterally, makes the lumbar spine unstable. PMID- 2267609 TI - Pathomechanism, pathogenesis, and results of treatment in cervical spondylotic myelopathy caused by dynamic canal stenosis. AB - In this study, the pathomechanism and pathogenesis of dynamic canal stenosis caused by cervical instability in patients with cervical spondylotic myelopathy and the validity of the concept of instability are clarified by analyzing the results of treatment in 53 cases. In cases of cervical spondylotic myelopathy caused by dynamic canal stenosis, the authors found that the posterior slide of the vertebral body occurs as a result of degeneration in the cervical spine due to aging changes, and that the dynamic sagittal diameter of the spinal canal decreases with an increase of the degree of posterior slide. This is followed by gradual aggravation of the clinical symptoms. Continuous cervical traction was found to be the first choice of treatment. Surgical treatment is indicated in cases in which the traction was ineffective, or even when it was effective, in cases in which the Japanese Orthopaedic Association (JOA) score remained low or when there was a tendency toward rapid aggravation of symptoms. It was demonstrated that the shorter the duration of the myelopathy, the better the results of treatment obtained. A limit of the dynamic sagittal diameter of the spinal canal of 12 mm was considered as valid. PMID- 2267610 TI - Intersegmental spinal flexibility with lumbosacral instrumentation. An in vitro biomechanical investigation. AB - Flexibility of the porcine lumbosacral spine was measured after application of six different types of surgical instrumentation, and in a control state. Fifteen adult pig spines were tested with flexion, extension, lateral bending, and axial rotation torques applied to the upper end with the pelvis fixed. Instrumentation was applied across two lumbar segments and the lumbosacral level (L5-6, L6-7, and L7-S1). Stereophotogrammetry was used to track markers applied to each vertebra. Intersegmental motion was measured as three angles and as the relative linear translation of adjacent transverse processes and spinous processes. Results showed that all instrumentation systems reduced intersegmental motion compared with the control state, except for minimal reduction at L5-6 by Harrington instrumentation in all loading directions, especially axial rotation. The pedicle screw systems were always the most rigid. After applying instrumentation, there were differences in the motion occurring at different anatomic levels, most commonly with the least motion occurring in the middle of the instrumented segment (L6-7). When intervertebral motion was expressed as the linear motion between adjacent spinous and transverse processes, the usual site of posterolateral fusion, it was 0.6 to 1.8 mm per degree of angular motion at the transverse processes and 1.3 to 2.1 mm per degree at spinous processes. PMID- 2267611 TI - Problems and solutions of pedicle screw plate fixation of lumbar spine. AB - Fifty-seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine. Eleven percent of patients had neurologic problems postoperatively and 3.5% (two patients) had severe sensory impairments. All patients had this complication in the early phases of the study. Of 297 screws, 17 broke, ie, 5.7%. These breakages occurred in 12 of 57 patients (21%). In patients with spondylolisthesis, the degree of slip correction averaged 53% postoperatively, which decreased to 35% at the 1-year follow-up. Slip angle was maintained after correction. Pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis. The surgeon must be fully trained in methodology. It is recommended that screw and plate materials be improved to prevent screw breakage. PMID- 2267612 TI - Magnetic resonance imaging of lumbar disc herniation. Comparison with myelography. AB - Fifty-three patients with surgically confirmed lumbar disc herniation at 55 levels were studied retrospectively to compare the diagnostic accuracy of high field strength surface coil magnetic resonance imaging (MRI) with that of myelography. Disc herniation was classified into three groups according to MRI findings, namely, unilateral single-disc herniation, central single-disc herniation, and multilevel disc herniation. Magnetic resonance imaging diagnosis of unilateral single-disc herniation was extremely reliable, so myelography was considered to be unnecessary. Conversely, MRI findings of central single-disc herniation and multilevel disc herniation were less definite, in that myelography was necessary in locating the disc causing symptoms. PMID- 2267613 TI - Ultrasonic level diagnosis of lumbar disc herniation. AB - Although the use of diagnostic ultrasound to measure the spinal canal has been proposed, the value of ultrasound for lumbar disc herniation has not been yet fully assessed. The purpose of this investigation was to evaluate the effectiveness of ultrasound in the level diagnosis of herniated nucleus pulposus. Prospective ultrasound examinations were performed on 80 consecutive patients with clinically suspected lumbar disc herniation. In 41 discs of those 40 patients with surgically confirmed lumbar disc herniation, there were 32 discs (78%) with true-positive ultrasound diagnoses, 37 discs (90%) with true-positive myelographic diagnoses, and 20 patients (50%) with true-positive neurologic diagnoses. Conversely, ultrasound diagnoses showed positive echogram in 24 (60%) of 40 nonoperative patients. These results suggest that ultrasound is of value as an aid for diagnosing the level of lumbar disc herniation. PMID- 2267614 TI - The system and procedures of percutaneous intradiscal laser nucleotomy. AB - Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory. The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation. After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue. The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method. PMID- 2267615 TI - Unstable lumbar spine without hypermobility in postlaminectomy cases. Mechanism of symptoms and effect of spinal fusion with and without spinal instrumentation. AB - The morbid conditions of unstable lumbar spine that are not associated with hypermobility in postlaminectomy cases were studied. The dura and the nerve roots with adhesion could be affected by minimal movement of the spine, which seemed to be the mechanism of symptoms of instability without hypermobility. The effects of spinal instrumentation on this particular instability were studied. The spinal instrumentation provides instantaneous rigid fixation, and maintains it until fusion is obtained, which might prevent adhesion, new bone formation, and re stenosis. Spinal instrumentation seemed to be the effective treatment for this particular instability. PMID- 2267616 TI - Lumbar trapezoid plate for lumbar spondylolisthesis. A clinical study on preoperative and postoperative instability. AB - The authors studied the effects of a "lumbar trapezoid plate" (spinal plate and pedicle screwing), performed for lumbar spondylolisthesis, observing the effect on the remaining adjacent discs with regard to preoperative and postoperative instability. The authors examined changes in preoperative and postoperative lumbar ROM (range of motion), displacement of motor unit levels, and occurrence of instability in the remaining discs, such as horizontal and rotational displacement, in 26 patients who were followed up for a mean of 29 postoperative months; 13 patients had spondylolytic spondylolisthesis and 13 patients degenerative spondylolisthesis. The authors studied the effects of the fused vertebral angle and reduction of spondylolisthesis on the remaining upper and lower adjacent discs and the preoperative and postoperative fused disc heights. Intervertebral fusion must affect the remaining adjacent discs, but compensatory function of the remaining motor unit level was more influenced by the fused intervertebral angle than by repositioning of the spondylolisthesis. Fusion at a physiologically lordotic position is quite necessary. For this purpose, it is considered important to prevent grafted bones of the posterior lumbar interbody fusion (PLIF) from collapse and to maintain the achieved alignment of the lumbar spine. PMID- 2267617 TI - Natural history of degenerative spondylolisthesis. Pathogenesis and natural course of the slippage. AB - To clarify the natural course of degenerative spondylolisthesis, the mechanism and progression of disk slippage were studied clinically and radiographically in 40 patients. Progressive slippage was observed in 12 patients (30%). No progression of slippage was noted in patients who showed narrowing of the intervertebral disk, spur formation, subcartilaginous sclerosis, or ossification of ligaments. These suggest that the mechanisms of spinal restabilization prevent progression of the disease. General joint laxity was observed in many patients (65%), and this was believed to be involved in the pathogenic mechanism of this disease. There was no correlation between the clinical symptoms and progression of slippage. These findings suggest that careful consideration of the natural mechanisms of spinal restabilization as well as the natural course of the disease is important. PMID- 2267618 TI - Long-term results of anterior interbody fusion for treatment of degenerative spondylolisthesis. AB - Thirty-nine patients, 34 women and five men, underwent anterior decompression and interbody fusion for degenerative spondylolisthesis between February 1958 and August 1988. Their average age at surgery was 51 years (range, 34-74 years), and their average follow-up period was 12 years 7 months (range, 6 months to 30 years). Clinical evaluation was done by the score rating system of the Japanese Orthopaedic Association (JOA Score). Patients with JOA scores of 25 points or more were rated as "satisfactory." Survivorship was analyzed by the method of Kaplan and Meier to determine the cumulative percentage of patients with satisfactory results. The following results were obtained: Seventy-six percent of the patients had satisfactory results for 10 years after the anterior interbody fusion, 60% for 20 years, and 52% for 30 years. Irrespective of their age at surgery, the patients generally maintained satisfactory results up to 65 years of age. PMID- 2267619 TI - Clinical study on stability of combined distraction and compression rod instrumentation with posterolateral fusion for unstable degenerative spondylolisthesis. AB - The authors examined the stability of combined distraction and compression rod instrumentation with posterolateral fusion in 40 consecutive patients with unstable degenerative spondylolisthesis. All operations were performed by floating fusion of L3-4 or L4-5 after decompression procedures. Mobility at the fused level was checked every 4 weeks after operation by the disc space angle on the functional radiographic films without brace. The average period of postoperative follow-up was 26 months. In 30 patients, no mobility was found at any time. In six patients, any mobility disappeared within 24 weeks, and in three patients, within 1 year. Pseudoarthrosis was found in one patient. The solid fusion rate was 97.5%. The values of percent slippage and slip angle were slightly improved. Lumbar lordosis was in the normal range at follow-up. PMID- 2267621 TI - Juvenile lumbar herniated nucleus pulposus in monozygotic twins. PMID- 2267620 TI - Total sacrectomy and reconstruction for huge sacral tumors. AB - The authors carried out successful total sacrectomy in three cases, two with giant cell tumors and one with a chordoma. The anterior and posterior approach is feasible for resecting huge sacral tumors en bloc, but it is important to reconstruct the continuity between the pelvic ring and spinal column using spinal instrumentation and sacral rods or AO plates. As total sacrectomy is a large scale, time-consuming, and collaborative operation, two or three teams should be used in relays. Both pelvic and spinal surgical techniques are required. Post operatively the patient can stand within 3 to 6 months and well-planned rehabilitation allows ambulation. In spite of the serious structural and neurologic damage caused, total sacrectomy can be rewarding procedure in terms of improved morbidity and mortality. PMID- 2267622 TI - A dorsally displaced free fragment of lumbar disc herniation and its interesting histologic findings. A case report. PMID- 2267623 TI - An 80-year-old patient with thoracic disc herniation. PMID- 2267624 TI - The optimum spine. PMID- 2267625 TI - Molecular cloning of a mammalian gene involved in the fixation of UV-induced mutations. AB - A mammalian DNA damage tolerance gene has been isolated by DNA transfection and cosmid rescue. Following cotransfection of mouse genomic DNA and pSV2neo into SVM, the UV hypersensitive mutant Indian muntjac cell line, clones with a 1.7 to 2.0-fold greater D37 value for UV killing were isolated. This trait was carried through three rounds of transfection. A neo gene and flanking sequences from a tertiary transfectant were cloned by cosmid rescue. The cosmid clone confers UV resistance to SVM and improves the ability of the cell to replicate UV damaged DNA. This replication appears to be error-prone; UV-induced 6-thioguanine resistant mutants occur four to fivefold more frequently than in SVM or a wild type Indian muntjac line. Thus, the gene isolated is not homologous to that defective in SVM. We believe that this is the first mammalian gene to be isolated that is directly involved in mutation fixation. PMID- 2267626 TI - Genetic analysis of a vital mammalian housekeeping locus using CHO cells that express a transfected mutant allele. AB - We describe a novel approach for the isolation of null mutations in a vital Chinese hamster ovary (CHO) cell housekeeping gene. Our experimental strategy required introduction of an expressible DNA clone encoding a recessive emetine resistance allele of ribosomal protein S14 into wild-type CHO cells. Transgene heterozygote (TGH) cell lines, which harbor multiple emetine-resistance S14 transgenes, survive mutations that inactivate the CHO RPS14 locus by virtue of the transgenes' biological function. Null mutations in RPS14 yield TGH clones that display the transgene's drug-resistance phenotype. A large collection of emetine-resistant clones was isolated from one TGH cell line and shown to consist of three types of S14 mutations: (1) nonsense null mutations in the RPS14 protein coding sequence; (2) missense null mutations that affect S14 amino acid residues that have been conserved stringently during eukaryotic evolution; and (3) a recurrent missense mutation that results in a new, functional RPS14 emetine resistance allele. PMID- 2267627 TI - Zinc treatment, metallothionein expression, and resistance to cisplatin in mouse melanoma cells. AB - Metallothioneins (MTs) protect cells from the toxic effects of heavy metals. It has been suggested that they play a role in cellular resistance to alkylating agents and ionizing radiation because of the coincidence of cadmium- and drug resistance and by virtue of the reactivity of MT with free radicals. We report the analysis of mouse B16 melanoma cell lines with high and low constitutive MT expression. In these cells, both cisplatin and cadmium resistance were associated with constitutive MT accumulation in the absence of heavy-metal induction. However, in cells with high constitutive MT expression (where zinc treatment did not induce increased MT expression), cisplatin resistance, but not cadmium resistance, was increased approximately twofold by zinc treatment. Methotrexate resistance also was increased by zinc treatment in some cases. We conclude that MT is associated with cisplatin resistance, but that effects of heavy-metal treatment other than MT induction are also responsible for cisplatin and methotrexate, but not cadmium, resistance. PMID- 2267628 TI - Complementing mutant alleles define three loci involved in mannosylation of Man5 GlcNAc2-P-P-dolichol in Chinese hamster ovary cells. AB - Dolichol-linked oligosaccharides consisting of two N-acetylglucosamine, nine mannose, and three glucose residues (Glc3Man9GlcNAc2) are transferred to proteins that contain the consensus sequence Asn-X-Ser/Thr. This transfer occurs upon protein import into the lumen of the endoplasmic reticulum. An intermediate in the biosynthesis of the Glc3Man9GlcNAc2 lipid-linked oligosaccharide contains two GlcNAc and five mannose residues. This intermediate serves as a substrate for further mannosylation and glucosylation before transfer to protein. The addition of the sixth mannose residue to this intermediate requires the enzyme mannosyltransferase VI and the mannose donor, mannose-P-dolichol. Several different CHO cell line mutants that fail to efficiently catalyze this transfer have been described. In this report, we examine seven independent mutant cell lines with various biochemical phenotypes and demonstrate that all can be assigned to one of three genetic complementation groups. One mutation affects mannose-P-dolichol biosynthesis (Lec15), three affect dolichol phosphate biosynthesis (Lec9), and three appear to affect the functional orientation of enzyme substrates (PIR). PMID- 2267629 TI - The IL-1 alpha and beta genes are closely linked (less than 70 kb) on mouse chromosome 2. AB - The murine IL-1 alpha and IL-1 beta genes encode structurally and evolutionarily related cytokines that exert a regulatory role in numerous physiological processes including hemopoiesis. Previous studies have shown these genes to be closely linked in the F region of mouse chromosome 2. Here we show, using pulsed field gel electrophoresis, that the IL-1 alpha and beta genes of the CBA/H mouse are very closely linked and contained within a SmaI genomic fragment of approximately 70 kb. From conventional and PFGE analyses we suggest that IL-1 beta lies 5' to IL-1 alpha and that the two genes are in the same orientation and separated by approximately 50 kb. The apparent clustering of such hemopoietic genes is discussed in relation to evolutionary tandem gene duplication and possible associations with chromosomal fragile sites and leukemogenesis. PMID- 2267630 TI - Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: implications for cell and gene therapy. AB - An assessment of the replicative life-span of myoblasts is of fundamental importance in designing treatment strategies for Duchenne muscular dystrophy (DMD) based on cell or gene therapy. To ascertain myoblast life-span, or the total number of cell divisions of which a myoblast was capable, we serially passaged and counted the progeny of individual myoblasts until they senesced. We compared the life-span of myoblasts from eight DMD patients with controls: three individuals with no known neuromuscular disease, three DMD carriers, and three patients with other muscle degenerative diseases. A decline in replicative capacity was observed with increasing donor age, which was markedly accelerated for DMD relative to control myoblasts. The average myoblast from a 5-year-old control was capable of 56 doublings, or a potential yield of approximately 10(17) cells per cell. By contrast, at 2 years of age, the typical age at clinical onset, only 6% of DMD myoblasts had a life-span of 50 doublings in tissue culture, and by age 7 DMD myoblasts capable of 10 doublings were rare. Our results suggest that the myoblasts (satellite cells) of even the youngest DMD patients have undergone extensive division in an attempt to regenerate degenerating myofibers. These findings have implications for therapeutic intervention in DMD involving genetic engineering and myoblast implantation. PMID- 2267631 TI - The Chinese hamster V79 cell mutant V-H4 is phenotypically like Fanconi anemia cells. AB - It has been shown by genetic complementation analysis that a mitomycin C sensitive mutant (V-H4) of Chinese hamster V79 cells is the first rodent equivalent of Fanconi anemia (FA) group A. The V-H4 mutant shows many typical characteristics of cells derived from FA patients. V-H4 cells exhibit increased sensitivity towards cross-linking agents as MMC (approximately 30-fold), cis-DDP (approximately 10-fold), DEB (approximately 10-fold), and PUVA (approximately 1.6 fold), but an only slightly increased sensitivity to monofunctional alkylating agents (EMS and MMS) and actinomycin D. V-H4 cells are also moderately sensitive to adriamycin (1.6-fold), and not sensitive to H2O2. The levels of chromosomal aberrations induced by MMC and cis-DDP treatment are higher (4- to 6-fold) in V H4 cells than in the wild-type V79 cells. Genetic complementation analysis with other Chinese hamster mutants hypersensitive to MMC (irs1, irs1SF, UV20 and UV41) indicates clearly that V-H4 belongs to a different, new complementation group. This unique mutant is very stable and can serve as a vehicle to isolate the complementing FA-A gene from normal human DNA. PMID- 2267632 TI - Chromosomal localization of the gene for a human cytosolic thyroid hormone binding protein homologous to the subunit of pyruvate kinase, subtype M2. AB - A cDNA for the gene that encodes a human cytosolic thyroid hormone binding protein (p58) recently has been isolated and sequenced. Analysis of the p58 sequence indicates that it is identical to the subunit of pyruvate kinase, subtype M2. By in situ hybridization, the gene for p58 was mapped to 15q24-25. This localization shows that the p58 gene is not linked to the L-type of pyruvate kinase, which is located on chromosome 1. The p58 gene was found to be activated in several forms of cancer. Current localization will permit us to assess the effect of alterations involving chromosome 15 on the structure and activity of the p58 gene in neoplasms or chromosome syndromes. PMID- 2267634 TI - [Diagnosis and differential diagnosis of choroidal osteoma with special reference to CT]. PMID- 2267633 TI - Gene mapping of mouse laminin A and B2 subunits using mouse-Chinese hamster somatic cell hybrids. AB - Laminin is a multichain extracellular matrix glycoprotein found primarily in basement membranes. The molecule is made up of three subunits, designated as A, B1, and B2. Using an 850-base cDNA probe for the mouse laminin A-chain and a 1000 base cDNA probe for the mouse laminin B2 chain, we have screened mouse-Chinese hamster somatic cell hybrids in order to assign the genes for each of these polypeptides to their respective mouse chromosome. We have determined that the mouse laminin B2-chain gene is located on chromosome 1 (confirming this assignment) and the laminin A-chain gene is located on chromosome 17. PMID- 2267635 TI - [Computed tomography of the pancreas]. PMID- 2267636 TI - [Psoas compartment disease--a forerunner of an internal psoas abscess?]. PMID- 2267637 TI - [Computed tomography of the retroperitoneum]. PMID- 2267638 TI - [The clinical use of a new contrast medium injector for computed tomography]. PMID- 2267639 TI - [Intravascular ultrasound. Methods and diagnostic significance]. PMID- 2267640 TI - Ethnographic research: a qualitative research approach to study of the interdisciplinary team. AB - Ethnography, one of many kinds of qualitative research, employs cultural theory, which emphasizes part-whole relationships, context, and multiple perspectives. Theory and method are intrinsically related. In ethnographic research, the primary instrument is human. Multiple observations, researchers, and sources of data contribute to the soundness of the study. This paper describes ethnographic research utilizing the study of interdisciplinary team-work as an exemplar. PMID- 2267641 TI - Psychosocial oncology research. AB - In recent years, increased attention has been paid to psychosocial aspects of cancer treatment, recovery and survivorship because oncology health professionals have observed that psychological and social variables can influence the medical outcomes and quality of life of cancer patients. A number of theoretical and conceptual frameworks which might guide research in this field are suggested. Next, several methodological issues of concern to psychosocial; oncology researchers are examined. This is followed by a discussion of recent important findings from psychosocial oncology research and of their implications for social work practice. Finally, recommendations for future research in the field are offered. PMID- 2267642 TI - The bio-medical environment and its challenge for social work research. PMID- 2267643 TI - Trends in maternal and child health care: implications for research and issues for social work practice. AB - Trends are reviewed in four areas of maternal and child health care: (1) prenatal care; (2) infant mortality; (3) teenage pregnancy; and (4) HIV infected mothers and infants. The purpose of this review is to identify major trends in these programmatic areas, key indicators of physical-social health risk and survival, and central issues relevant to research and social work practice. Attention is directed to the status of research, and the usefulness of existing data sets available to researchers in the four programmatic areas of maternal and child health care under review. Emphasis is given to the importance of the integration of theory, research findings, and practice. PMID- 2267644 TI - Research on organizational issues in health care social work. AB - A rich body of knowledge spans organizational topics relevant to the practice, conceptual development and planning of social work health care services. At a time when health care organizations are experiencing major changes in their structure and financing; organizational research informs both the system adjustments and leadership which social work can offer the health care field. Organizational research on health care social work is grouped into three categories: management and administrative issues; interprofessional and interorganizational relations; and service delivery topics. Within each category, the major issues are presented with single site and multi-site research reviewed. Recommendations to improve the contributions of this body of research include greater attention to methodological rigor in designing and implementing research projects. PMID- 2267645 TI - Observations on the scientific base of health social work. AB - This article examines aspects of social work in health care from a philosophy of science perspective, which suggests different ways of conceptualizing and defining variables ranging from service recipients to principles undergirding social work intervention. Focus is given to the relationships among theory, practice, and research in social work by considering the nature of clinical theory; health social work theory; and theory grounded research. PMID- 2267646 TI - Research on practice with groups in health care settings. AB - The theoretical underpinnings for group practice in health settings include theories pertaining to the individual, the small group, and systems. These theories remain largely untested due to attitudes of both the clinician and researcher, methodological problems related to the complexities of individual and group variables, the lack of a consistent common language, and limited availability of practical and sound empirical measures. Most of the literature is anecdotal. There are some descriptive and outcome studies but little research addresses the relationship of process to outcome. Suggestions are offered to begin bridging this gap. PMID- 2267647 TI - Photodynamic therapy of esophageal carcinoma. AB - Photodynamic therapy (PDT) utilizing either hematoporphyrin derivative or Photofrin II is proving to be an effective modality in the treatment of early superficial (ES) or advanced invasive (AI) carcinoma of the esophagus. An argon pumped dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel of a gastroscope after intravenous injection of photosensitizer. Between 1982 and 1989, 20 patients (ES = 6; AI = 14) were treated in this manner. Complete remission was obtained in 4 of 6 ES cases, and the mean survival after PDT alone or in combination with other therapy was 27 months. Five patients remain alive to date. In the AI group, significant remissions were obtained in 6 cases while partial remissions were observed in another 8. The mean dysphagia grade improved from 4.0 to 2.8. We conclude that PDT is efficacious in the treatment of ES esophageal cancer, where complete remission may be achieved, and as palliative therapy in advanced cases to alleviate dysphagia. PMID- 2267648 TI - Preoperative staging of gastrointestinal tumors by endosonography. AB - Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date. PMID- 2267649 TI - Needle biopsy of submucosal lesions of the gastrointestinal tract. AB - Needle biopsy of submucosal lesions is an important addition to the diagnostic capabilities of gastrointestinal endoscopy. A series of 22 cases is described employing a guillotine needle to diagnose submucosal lesions, 4 of which were infiltrating adjacent carcinomas. The specimens obtained were sufficient for firm histological diagnosis in 20 cases. There were no complications apart from minor bleeding in 1 case. PMID- 2267650 TI - Repeat percutaneous endoscopic gastrostomy (PEG): an outpatient procedure. AB - Patients who have previously undergone percutaneous endoscopic gastrostomy (PEG) with subsequent PEG removal occasionally require elective repeat PEG. Adhesion of the stomach to the abdominal wall after the original PEG allows repeat PEG to be performed as an outpatient procedure and full-volume tube feeding to be started immediately. Elective repeat PEG was performed in ten patients. Repeat PEG was performed at the site of the original PEG in all cases. Six of the ten repeat PEGs were performed as an outpatient procedure. No complications were attributed to repeat PEG, and full-volume tube feedings were tolerated in all cases when attempted. To obviate the need for repeat PEG, we recommend immediate replacement after inadvertent PEG removal and avoiding elective removal of PEGs used in patients with long-term neurologic impairment for at least 6 months. PMID- 2267651 TI - Oxygen saturation monitoring during endoscopy. AB - The role of monitoring during endoscopy is not clearly defined. We have prospectively investigated continuous arterial oxygen saturation (SaO2) monitoring in 326 patients undergoing upper endoscopy (EGD) and 90 undergoing colonoscopy. Automated blood pressure recording was evaluated in 278 of these patients. SaO2 desaturation (less than 90%) occurred in 17.8% of patients undergoing EGD and 12.9% undergoing colonoscopy. Systolic blood pressure abnormalities (greater than 200 or less than 90 mmHg) occurred in 19.8% of EGD patients and 19.6% of colonoscopy patients. Treatment based on these abnormalities was required in 4.3% of patients during EGD and 8.8% during colonoscopy. A history of pulmonary or cardiac disease predicted increased risk during colonoscopy, while cardiac disease and age 60 years or above predicted desaturation during EGD. Pulse oximetry and automated blood pressure monitoring was especially valuable during endoscopy in the elderly and patients with cardiac or pulmonary disease. It may be used as a guide to therapeutic intervention and to avert major cardiopulmonary complications. PMID- 2267652 TI - Evaluation of safe, effective intravenous sedation for utilization in endoscopic procedures. AB - The prevention of anesthetic mishaps during endoscopic procedures is of great importance to physicians in training. With the large number of such procedures performed each year, even infrequent adverse anesthetic reactions may result in a significant number of problems. To establish the safety and efficacy of an anesthetic regimen using intravenous meperidine and diazepam, all endoscopic procedures performed at one teaching institution in a 4-month period were retrospectively analyzed with regard to: (1) type and dosage of sedation/anesthesia, (2) endoscopic procedure involved, (3) effect of any underlying disease state, (4) side effects, (5) endoscopic complications, and (6) overall patient acceptance. A total of 716 patients underwent 913 endoscopic procedures with 876 separate anesthetic/intravenous sedations. General anesthesia was utilized in 44% of the 155 pediatric procedures. In the adult patients, intravenous sedation was administered by a physician-in-training under supervision except in 9% of cases (66 patients) when intravenous sedation utilizing alternative agents was given by the anesthesia department. The dose of sedation used (per body weight) declined with increasing age in the pediatric group (0-19 years). The adult dose remained constant for the next eight decades of life (meperidine 0.76 +/- 0.33 mg/kg: diazepam 0.12 +/- 0.08 mg/kg). In the adult group, 758 procedures were performed: 371 patients underwent esophago gastroduodenoscopy, 258 colonoscopy, 36 endoscopic retrograde cholangiopancreatography, 40 flexible sigmoidoscopy, and 51 percutaneous endoscopic gastrostomy. Anesthetic-related complications (transient apnea and itching), were noted in two patients, and naloxone was utilized to reverse oversedation in a further 17 (2.56%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2267653 TI - Drainage-tube penetration into the gastric lumen, mimicking a high-volume enterocutaneous fistula. The significance of postoperative endoscopy. AB - Two cases of drainage-tube penetration of the gastric lumen, presenting as high output enterocutaneous fistulas after total gastrectomy and liver hydatid disease surgery are reported. This rare complication and the value of endoscopic diagnosis and treatment in the early post-operative period are emphasized. PMID- 2267654 TI - [The radiotherapy of primary extranodal non-Hodgkin's lymphoma of the nasopharynx]. AB - Primary non-Hodgkin's lymphoma occurs quite seldom in the nasopharynx, therefore reports on this topic are rare in medical literature. The treatment results of 30 irradiated patients (40 to 60 Gy) are presented. The period of the study ranges from 1960 to 1985. 13 patients with low grade lymphoma and 17 patients with high grade lymphoma according to the Kiel classification form the basis of this study. The overall actuarial 5-year survival rate is 24%. This also applies for the subgroups of low grade and high grade lymphomas with a 5-year survival rate of 24%, respectively. The evaluation of the patients without generalization in the course of disease shows that the prognosis of stage IE patients with 43% was superior to the one of stage IIE patients with 25% (p less than 0.001). Only patients with lymphoma limited to the nasopharynx survived longer than five years (46%), but none of the patients with simultaneous spread to the nasal cavity, the oropharynx and/or the base of the skull. Local and regional recurrences were rare. However, a generalization of the disease occurred more often (20%), mainly due to insufficient staging in former years. Long-term sequelae of the radiation therapy like rhinitis or pharyngitis sicca were registered occasionally. At present, locoregional radiation therapy is recommended for stage IE and IIE low grade lymphomas and stage IE high grade lymphomas of the nasopharynx. PMID- 2267655 TI - [The radiation reaction of the lung following the treatment of breast carcinoma with telecesium--the correlation with the dose-time relationship]. AB - 51 mamma carcinoma patients underwent postoperative telecaesium irradiation (50 Gy). Chest radiograms were taken preceding the treatment and following it by eight to ten weeks. By reason of the results it can be supposed, that the unavoidable lung reaction due to radiotherapy can be decreased and partly avoided by adequate fractionation. PMID- 2267657 TI - [The results of the endocavitary irradiation of early-stage rectal tumors]. AB - Intracavitary contact radiotherapy was used according to the guidelines of J. Papillon in 91 patients with early rectal tumors (72 adenocarcinomas and 19 villous adenomas) at the Dijon Cancer Institute. Most of the patients were referred because of poor surgical risk. Ten patients had interstitial implants in addition, 96% of the patients had a complete response. The local control rate after five years was 74% (67/91). Including salvage the ultimate control rate was 91% (83/91). 85% (77/91) had preservation of the sphincter function. The size of the rectal cancer and the degree of rectal wall invasion were of prognostic impact as proposed by the clinical staging system of Dijon. PMID- 2267656 TI - Pleural effusion in patients with isolated chest wall recurrences of breast cancer. AB - The reports of 66 patients with isolated chest wall recurrences of breast cancer after mastectomy who developed a pleural effusion were analyzed. The location of the pleural effusion was ipsilateral in 71.2%, contralateral in 21.2% and bilateral in 7.6%. The cumulative incidence of ipsilateral effusions after onset of chest wall recurrence is 81.4% within two years. The high frequency of ipsilateral effusions and the shorter interval after chest wall recurrence supports the hypothesis of locoregional tumor progression to the pleural space in patients with chest wall recurrences. High-voltage irradiation of the thoracic wall might effectively reduce the spread through to the pleural space. PMID- 2267658 TI - [Preoperative radiotherapy in rectal carcinoma. I. The effect of irradiation on the tumor volume]. AB - We studied an effect of preoperative radiation upon the change of tumor volume in rectal carcinoma. As a preliminary study, tumor volume of 15 cases of rectal carcinoma with no preoperative irradiation was estimated preoperatively using the transrectal ultrasonography, and were compared with those determined by resected specimens after operation. As a result, there was a parallel relationship between the two values, and mean estimation error rate was 14.6%. Next, the same method was applied to 15 patients with rectal carcinoma who underwent preoperative radiation in order to detect the reduction rate of tumor volume after radiation therapy (42.6 Gy). As a consequence, 80% of cases exhibited the reduction rate more than 50% with an average of 61.7%. It was suggested that the determination of pre- and postoperative tumor volume would be beneficial to evaluation of preoperative radiation therapy as well as decision of the optimal dose of radiation in rectal carcinoma. PMID- 2267659 TI - Radiotherapy of primary brain tumours in the region of the third ventricle. AB - Patients (n = 18) with a primary brain tumour near the third ventricle and treated by radiotherapy were retrospectively analysed. Four different subgroups of patients, according to the histology (germ cell tumours, astrocytomas, other histologies, no histology) were separately discussed. Third ventricle tumours were more frequent in younger patients (less than 30 years). Five years actuarial disease free survival was 62%. Six out of 18 patients died of disease, the others are currently alive without evidence of disease. PMID- 2267660 TI - [The influencing factors and interfering effects in the control of the power distributions with the BSD-20000 hyperthermia ring system. 1. The clinical observables and phantom measurements]. AB - A new generation of annular-phased-array systems BSD-2000 has been clinically applied in a pilot study. Therapeutic intratumoral temperatures greater than 42 degrees C were obtained in 15/15 sessions with six patients. However, the control of power deposition pattern has to be improved in order to increase the therapeutic gain and to guarantee an efficient therapy. A retrospective analysis of clinical phenomena has been performed by phantom set-ups because the power deposition pattern cannot be determined during therapy. Phantom measurement techniques are outlined, specifically phantom materials and visualization of power distributions. The problem of focus balance and frequency choice is illustrated by self-developed phantoms (liquid crystal sheets, light-emitting diode-arrays). Especially, the limitation of modeling calculations is demonstrated. PMID- 2267661 TI - Radiation effect of gadolinium-neutron capture reactions on the survival of Chinese hamster cells. AB - In gadolinium-neutron capture reactions, prompt gamma rays with an energy spectrum of up to 7 MeV, X-rays and electrons are released. We measured the effect of radiation as a result of capture reactions on cultured Chinese hamster cells. Cells in the medium containing 5000 ppm gadolinium were exposed to thermal neutrons from a nuclear reactor. The survival curve for those cells exhibited a shoulder in the low neutron fluence region. The survival curve for cells exposed to thermal neutrons in the absence of gadolinium was a simple exponential function. To obtain 10% survival levels, 5.4 x 10(12) neutrons/cm2 were required for cells irradiated in the absence of gadolinium, and 1.55 x 10(12) neutrons/cm2 for those irradiated in the presence of gadolinium. The therapeutic ratio in gadolinium-neutron capture therapy depends on the difference in 157Gd concentrations between the tumor and normal tissues. Thus, our current effort has been to develop a method of selectively delivering 157Gd to tumors. PMID- 2267663 TI - Delayed nephrotoxic effects of cadmium and their reversibility by chelation. AB - A single injection of CdCl2 (15 mumol/kg) together with 300 mumol/kg mercaptoethanol into adult male rats induced renal dysfunction only after a delay of at least 12 h; in contrast, the peak value of cadmium in renal cortex (34 +/- 3 micrograms/g) was reached within 2 h. The chelator methoxybenzylglucaminedithioate (MBGDT) rapidly reduced the renal Cd level by 2/3, primarily by extracting the metal from the sedimentable rather than the cytosolic fraction. MBGDT prevented the subsequent onset of malfunction, but only when given at an early stage after Cd administration (2 h). It follows that the renal damage seen after the initiation period is independent of the Cd concentration at that time. The changes occurring during initiation remain unexplained. PMID- 2267662 TI - Metabolism and pulmonary toxicity of intratracheally instilled cupric sulfate in rats. AB - Though copper (Cu)-handling workers are known to be at risk to develop metal fume fever and acute respiratory failure, very little is known about the metabolic fate and pulmonary toxicity of Cu compounds deposited in the lung. We have investigated time-course and dose-related changes in Cu contents, the production of metallothionein (MT) and inflammatory responses in the rat lung following intratracheal instillation of cupric sulfate (CuSO4). Intratracheally instilled Cu was cleared rapidly from the lung with a half-time of 7.5 h. Copper-binding MT was induced in the lung tissue following Cu instillation and the amount of MT increased with the dose of CuSO4. However, the production of MT contributed little to the accumulation of Cu in the lung. The pulmonary toxicity of CuSO4 was evaluated by examining time-course and dose-effect profiles of cytological and biochemical inflammatory indices (enzymes, protein and elements) retrieved in bronchoalveolar lavage fluids. These results revealed that the inflammatory indices reached maximum values in their activities and contents at 12 h to 3 days after instillation and a dose of 5 micrograms Cu/rat was sufficient to produce acute inflammatory responses in the rat lung. PMID- 2267664 TI - Measurement of steady-state blood concentrations in B6C3F1 mice exposed by inhalation to vinylidene fluoride. AB - The purpose of this study was to obtain data on blood concentrations of vinylidene fluoride (VDF), an important plastics monomer in B6C3F1 mice during inhalation exposure. A new method for sampling blood from mice during the exposures was developed. The technique used a pernasal exposure tube with an outer, sliding cylinder that allowed access to the heart through the thorax. Blood was removed from an anesthetized mouse via heart-puncture while the animal was being exposed to VDF. Concentrations of VDF were measured in blood of mice during 6-h exposures to nominal concentrations of 250, 3750, or 15,000 ppm VDF. A physiological model developed to simulate blood levels of VDF in rats was adapted for mice by incorporating physiologically realistic parameters for mice where appropriate (alveolar ventilation, cardiac output, blood flow to organs, and organ volumes) and by assuming that chemical-specific parameters such as tissue/blood partition coefficients determined for rats could also be applied to mice. Measured steady-state levels of VDF in blood of mice increased with increasing exposure concentration. For both the 15,000 and 3750 ppm VDF exposures, the experimentally determined data fell within the 95% confidence interval predicted by the physiological model. For the 250 ppm VDF exposure, the experimentally determined values for VDF in blood were lower than what was predicted by the model. Model predictions indicated that for mice, as observed for rats, levels of VDF would rise very rapidly, reaching steady-state within minutes of exposure, and that at the end of exposure, blood levels will decline rapidly. At the two lowest exposure concentrations, we were unable to detect VDF in blood taken 15 min or longer after cessation of exposure, suggesting that the post-exposure levels were at or below our limit of detection which was 4 ng VDF/ml blood. For the 15,000 ppm exposure VDF could be detected in blood up to 15 min post exposure. PMID- 2267665 TI - Hepatic and extra hepatic glutathione depletion and glutathione-S-transferase inhibition by monocrotophos and its two thiol analogues. AB - Effect of monocrotophos (MCP) and its thiol analogues (coded as RPR-2 and RPR-5) on hepatic and extra-hepatic glutathione (GSH) depletion and glutathione-S transferase (GST) inhibition was studied at 0.96, 1.23 and 3.0 mg/kg respectively 24 h after medication in rats. All the three compounds caused tissue specific depletion of GSH from hepatic and extra-hepatic tissues. Cytosolic GST activity was significantly inhibited in all the tissues, MCP being the most potent inhibitor. Both in vitro and in vivo data indicate that hepatic GST inhibiting potential of the three compounds lies in the order MCP greater than RPR-5 greater than RPR-2. In vitro effect of 3 compounds on GSH activation kinetics of GST demonstrate competitive inhibition by MCP and non-competitive inhibition by the two analogues. However, CDNB activation kinetics of the enzymes revealed mixed inhibition by all 3 compounds. The present study suggests that monocrotophos and its thiol analogues may bring about physiological upsets by altering GSH and GST dependent events in different tissues of exposed organisms. PMID- 2267666 TI - Effects of chronic exposure to ozone on pulmonary lipids in rats. AB - Ozone is the most toxic component of photochemical oxidant air pollution. Exposure to high concentrations of ozone produces a variety of toxic effects in the lung, but it is not known to what extent prolonged exposure to low concentrations of ozone may contribute to the development of chronic lung disease. Phospholipids, important components of cellular membranes and surfactant, are necessary for the maintenance of normal lung structure and function. In order to test the effects of chronic exposure to environmentally relevant concentrations of ozone on phospholipid metabolism in the lung, rats were exposed to clean air or to 0.12, 0.25 or 0.50 ppm ozone for up to 18 months. The content and biosynthesis of phospholipids in both lung tissue and bronchopulmonary lavage fluid (surfactant) were measured. Incorporation of [14C]acetate into lung tissue phospholipids, an estimate of overall biosynthesis, decreased significantly at some time points in the study, while tissue phospholipid content tended to increase with both ozone concentration and with age. No changes were detected in phospholipid content of bronchopulmonary lavage fluid. These findings did not support the hypothesis that prolonged exposure of rats to environmentally relevant concentrations of ozone results in either qualitative or quantitative deficits in the pulmonary surfactant system. PMID- 2267667 TI - GABA transporter protein cloned from rat brain. PMID- 2267668 TI - Fibrinogen as a major risk factor in cardiovascular disease. AB - Evidence has accumulated over the past ten years to implicate elevated plasma fibrinogen levels in cardiovascular disorders such as ischaemic heart disease, stroke and peripheral vascular disease. At a cellular level, insight has been gained into the molecular regulation of fibrinogen biosynthesis and the mechanisms through which fibrinogen may be involved in these disease processes. Here, Nigel Cook and David Ubben summarize this evidence and consider the possibilities for novel therapies targeted at fibrinogen. A variety of structurally diverse pharmacological agents, many of which were developed for their effects on plasma lipids, have serendipitously been found to lower plasma fibrinogen levels. PMID- 2267669 TI - Ultrasonography in gastroenterology: stethoscope of a gastroenterologist. PMID- 2267671 TI - Abdominal tuberculosis in children. AB - Problems in the management of abdominal tuberculosis in children are discussed with reference to 80 surgically proven cases. The protean clinical manifestation depends on the site and the extent of the disease and its complications. The clinical diagnosis is difficult because of the vague symptoms, non-specific signs, and non-availablity of specific diagnostic tests. The most common type of pathology seen in abdominal tuberculosis in the paediatrics age were adhesive variety followed by nodal type. Strictures of the small bowel are uncommon and hyperplastic variety is rarely seen in this age group. Response to the antitubercular drugs is excellent however, the post operative complications and mortality remain high. PMID- 2267670 TI - Current development in the pathogenesis of gallstones. AB - Demonstration in 1968, of the association of cholesterol supersaturation of bile with cholesterol gallstones paved the way to a physical-chemical basis for gallstone formation. It however, soon became clear that other factors including nucleation of cholesterol crystal, binding together of these crystals with mucin, and hypomotility of the gallbladder played an equally important role in gallstone formation. Although the molecular events that underlie these processes are far from clear, many loose ends are beginning to tie. One knot recently tied is that an increase in biliary arachidonyl lecithin may lead to increased prostanoid synthesis which may be responsible for increased mucin secretion as well as gallbladder hypomotility. Research on similar lines is being done to unravel the pathogenesis of pigment gallstones, but much less has been gained in that field. An interesting outcome of some recent work is that biliary micelles and vesicles are important not only for the solubilisation of cholesterol but also for that of bilirubin and calcium which are the major constituents of pigment gallstones. This observation opens a common ground for the formation of both types of gallstones. PMID- 2267672 TI - Faecal chymotrypsin assay in tropical and alcoholic chronic pancreatitis. AB - Faecal chymotrypsin (FCT) levels were estimated in a group of patients with tropical chronic pancreatitis (TCP) and compared with patients with alcoholic chronic pancreatitis (ACP), 'gastrointestinal' controls and 'healthy' subjects. Exocrine pancreatic insufficiency as assessed by low faecal chymotrypsin levels (less than 5.8 mu/g) were present in 85.7 per cent of TPC and 84.6 per cent of ACP patients. Mean FCT levels as well as the distribution of FCT values were similar in TCP and ACP patients and significantly lower than the two control groups (P less than 0.001). There was also no difference with respect to mean FCT levels between subgroups of TCP patients with and without diabetes and those with and without calcification. Faecal chymotrypsin assay is a simple test for diagnosis of chronic pancreatitis in gastroenterological centres in tropical countries. PMID- 2267673 TI - Pancreatic islet transplantation: utility of ductular obstruction and exocrine atrophy model? AB - Introduction of 'silent' exocrine atrophy (and endocrine 'enrichment') in pancreatic grafts following ductular blockade may have a role in human diabetes by circumventing currently elusive islet isolation/purification protocols. To explore this potential, pancreatic isografts were performed in 12 pairs of inbred Wistar NIN rats. Donor pancreatectomy was performed after distal clamping and canulation of common bile duct and injection of 0.5 ml. polyacrylamide gel (blocked n = 7) or normal saline (un-blocked n = 5) respectively. One to 2 m.m. fragments of the resulting mildly distended pancreases were transplanted in to 2 sites (renal capsule and iliac fossa subcutaneously) of cach recipient. Post operative biopsies of the transplanted grafts (unilateral nephrectomy and iliac fossa biopsies) revealed macroscopic and microscopic evidence of necrotizing pancreatitis in both the groups at both the sites (histiocytic and giant cell infiltration, fat necrosis and focal calcification with destruction of exocrine and endocrine cells) as early as 1 and 3 weeks. Possible detrimental factors include: volume and pressure of ductal injection, graft sites (confined spaces), post-operative wound infection and bio-compatibility of the material used for ductular blockade. PMID- 2267674 TI - Spirochetal dysentery: a case report and review of literature. AB - Spiral shaped bacteria have frequently been demonstrated from human faeces. Their role in causation of disease is, however, controversial; as they have been found to colonise the lower gastrointestinal tracts of both symptomatic and asymptomatic individuals. Here we report a case in which spiral shaped motile, gram negative and nonflagellated bacteria, probably belonging to the genus Borrelia, were demonstrated and associated with acute bloody diarrhea in a cardiac patient. The condition could successfully be treated with short course of Metronidazole. The relevant and up to date literature on this problem is also reviewed. PMID- 2267675 TI - Why can't we have a Santiniketan for medical education? PMID- 2267676 TI - Immunotherapy of tuberculosis. PMID- 2267677 TI - Drug combinations and the bioavailability of rifampicin. PMID- 2267678 TI - Patient compliance with tuberculosis treatment in Ghana: factors influencing adherence to therapy in a rural service programme. AB - In Agogo Hospital in the hills of Ashanti, Ghana, default and cure rates among 569 consecutive sputum-smear positive pulmonary tuberculosis (PTB) patients registered between 1984 and 1987 in a rural ambulatory non-supervised service program were analysed. Female gender, shorter home-to-clinic distances and younger age were significantly associated with higher cure and lower default rates. Within the district where liaison health workers paid home visits to PTB patients, the home-to-clinic distance effect on default was overruled by the effect of follow-up. Data from two surveys held in 1985 and 1987, among 68 and 49 PTB patients respectively, revealed that many patients visited healing churches but few admitted to having consulted traditional healers; that financial expenses for transport outweighed hospital charges; that lower educational levels were not associated with poorer compliance to therapy and that health education had improved significantly over the 2-year-period. It is concluded that intervention with liaison health workers and simple health education results in improved outcome in rural service tuberculosis programme. PMID- 2267679 TI - Improved immunotherapy for pulmonary tuberculosis with Mycobacterium vaccae. AB - We previously demonstrated that a single intradermal injection of 10(9) irradiation-killed M. vaccae, given 1 month after starting chemotherapy, caused significant changes in responses to mycobacterial antigens. Amongst 38 patients with pulmonary tuberculosis, 29% had lymphocytes responding to common myocobacterial antigens after the injection, compared with only 11% of 49 similar patients after an injection of saline (p less than 0.03). To increase the proportion of responders to these antigens, six modifications of the potentially immunotherapeutic injection, randomized with injections of saline, have been assessed by biochemical, clinical, haematological, immunological and radiological criteria. Subsequent lymphocyte proliferation to mycobacterial antigens enabled the modifications to be ranked in order of efficacy. Tuberculin plus murabutide plus 10(9) irradiated M. vaccae (36% of 25), an autoclaved preparation of 10(9) M. vaccae (45% of 22), and 2 x 10(9) irradiated M. vaccae (75% of 12) were the most effective. Antibody responses in several IgG subclasses to mycobacteria, but not streptococci, were also significantly increased by the most effective modifications over the 8 weeks following injection. Detailed radiological study showed that use of the autoclaved bacilli was followed by a delay in clearing of consolidation, but by better closing of cavities than was found in the control group, suggesting enhanced, or altered, immunological activity around the lesions. PMID- 2267680 TI - Increased prevalence of diabetes mellitus in patients with pulmonary tuberculosis in Tanzania. AB - Glucose tolerance was assessed, according to WHO diagnostic criteria, in 506 consecutive African patients admitted with sputum-positive pulmonary tuberculosis to the tuberculosis wards of Muhimbili Medical Centre, Dar es Salaam. Nine (1.8%) patients were known to have diabetes. Following a 75 g oral glucose tolerance test (OGTT) diabetes was diagnosed in a further 25 (4.9%) patients giving an overall crude diabetes prevalence rate of 6.7%. Impaired glucose tolerance (IGT) was present in 82 (16.2%) subjects. A repeat OGTT was carried out in the 25 patients found to have diabetic values after the first test. Eight (28%) of the 25 patients reverted to normal glucose tolerance after the second test, 6 (24%) to IGT, and 11 (48%) remained with blood glucose values in the diabetic range, giving a crude diabetes prevalence rate of 4%. In a survey of glucose tolerance, using similar methodology, in 693 members of an urban community in Dar es Salaam the prevalence rates of diabetes and IGT were 0.9% and 8.8% respectively. Diabetes was therefore at least four times as common in the tuberculosis patients (p less than 0.001), and IGT twice as frequent (p less than 0.0001). This study confirms the relationship between diabetes and tuberculosis. Those caring for patients with tuberculosis should be aware of the increased prevalence of diabetes in their patients, since failure to diagnose the problem may adversely affect prognosis. PMID- 2267681 TI - Adrenocortical function in patients with pulmonary tuberculosis. AB - Adrenocortical function was studied in patients with pulmonary tuberculosis and the findings compared with those in healthy subjects. Plasma cortisol levels in newly diagnosed patients were appreciably higher than in the healthy subjects (P less than 0.001). A normal (positive) response to ACTH (tetracosactrin) stimulation was observed in 35 (97%) of 36 healthy subjects, 15 (56%) of 27 newly diagnosed patients with tuberculosis and 5 (42%) of 12 chronic cases (i.e. those who had had the disease for more than 3 years); the difference between the healthy subjects and the two groups of tuberculosis patients was highly significant (P less than 0.001). Dexamethasone caused an appreciable decrease in the plasma cortisol levels of tuberculosis patients. Considering the diurnal variation of cortisol secretion, there was a steady decline in the cortisol levels between 08:00 and 20:00 in the healthy subjects (P = 0.02); in the tuberculosis patients, however, there was a decrease up to 16:00 followed by a significant increase (P = 0.05), and the mean value at 20:00 was similar to that at 08:00. PMID- 2267682 TI - Cutaneous vasculitis associated with tuberculosis and its treatment. AB - Two patients with pulmonary tuberculosis developed cutaneous vasculitis after antituberculosis treatment and a patient with tuberculous lymphadenitis developed vasculitis at presentation before drug therapy. The cutaneous vasculitis probably represented immunological reactions to tubercle bacilli and/or rifampicin with antibodies and immune complex formation. PMID- 2267683 TI - Tuberculosis of the thyroid bed presenting as recurrent medullary thyroid carcinoma. AB - A 69-year-old lady with previous medullary thyroid carcinoma treated by total thyroidectomy alone developed a swelling in the neck. This was thought to be a recurrence of her carcinoma but was found on investigation to be a tuberculous abscess of the thyroid bed. She was treated successfully by surgical drainage and antituberculous chemotherapy. PMID- 2267684 TI - Pulmonary disease caused by Mycobacterium asiaticum. AB - A 62-year-old male residing in Los Angeles, California, presented with a right upper lobe nodule associated with dry cough and weight loss. Mycobacterium asiaticum was isolated from sputum on two separate occasions. The patient was subsequently treated with four antituberculous drugs, with bacteriologic conversion. This is the first report of pulmonary disease caused by M. asiaticum in the United States. The bacteriologic, immunologic and clinical aspects are reviewed. PMID- 2267685 TI - [State of the hemostasis system in patients with malignant III-stage neoplasms of the maxilla and larynx]. AB - Hemostasis of patients with III stage malignant neoplasms of the maxilla and larynx was investigated. We examined 40 patients, 8 of which had maxillary tumor and 32 had laryngeal tumor. The age of the patients varied from 44 to 68 years. It was found that the patients with malignant neoplasms of the maxilla and larynx had hemostatic disorders which formed the thrombohemorrhagic syndrome. During the surgical intervention they displayed the hypocoagulation phase of the syndrome, which indicated the most dangerous prethrombotic state of the blood system. PMID- 2267687 TI - [Effects of helium-neon laser energy on the tissues of the middle ear in the presence of biological fluids and drug solutions]. AB - By means of biophotometry the coefficients of absorption and penetration depth of helium-neon laser radiation with a wavelength of 632.8 nm were measured. Measurements were made in the inflammatory mucous membrane of the tympanic cavity, mucous membrane of the tympanic-cavity infiltrated with the saline solution, cortical bone of the mastoid, cartilage of the auricle, blood, serum, exudate, 0.02% furacillin, 3% boric acid, 0.9% and 10% NaCl. These observations were used to develop an efficient method of laser therapy of the inflammatory and wound surface of the middle ear biological tissue, which formed the basis of a new procedure of the laser treatment of "closed" cavities of the middle ear in an early postoperative period after debridement or hearing repair surgery of suppurative otitis media which were filled with a transparent antiseptic solution. PMID- 2267686 TI - [Causes of late diagnosis of nasopharyngeal cancer]. AB - By the onset of specific therapy of 240 patients with nasopharyngeal cancer 96.6% of them were in stage III (20%) and stage IV (76.6%) of the disease. The causes of delayed diagnosis and therapy included inadequate oncology concern of out patient physicians, careless attitude of most patients towards their own health condition, low quality of physical examinations and limited diagnostic facilities. PMID- 2267688 TI - [Functional methods of study in the evaluation of the effectiveness of laser therapy of vasomotor rhinitis and some forms of prosopalgia]. AB - Highly sensitive instrumental methods such as rhinopneumography, rhinorheography, rheoencephalography and segmented sphygmography were used to measure the efficacy of contact laser therapy of the pterygopalatine ganglion to treat vasomotor rhinitis and trigeminal neuralgia. This method proved efficient in the case of the nervous form of vasomotor rhinitis, Sluder syndrome, and trigeminal neuralgia. Stable remission developed in 60% of patients. PMID- 2267689 TI - [Characteristics of vestibulo-ocular interactions in patients with unilateral lesions of the peripheral part of the vestibular system. Sinusoidal rotation. 3]. AB - In 40 patients with unilateral injury of the peripheral compartment of the vestibular system in the stage of decompensation (Group 1) and subdecompensation (Group 2), the vestibulo-ocular reflex (VOR) was investigated during sinusoidal rotation with the eyes closed. Group 1 patients showed a significant asymmetry of the VOR coefficient and a distinct shift of the VOR displacement towards injury during sinusoidal stimulation of any intensity. Group 2 patients displayed similar but less significant changes. PMID- 2267691 TI - [Diagnostic role of vestibular recruitment and nystagmic parameters]. AB - Electronystagmographic examination of 45 patients with peripheral and 22 patients with central lesions of the vestibular system was performed, using graded caloric and rotatory stimulation of labyrinths. It was demonstrated that functional and topical diagnosis of vestibular problems can be made with the aid of righting reflexes and vestibular recruitment. In this situation, it is important not only to detect the righting reflex but also to determine the nystagmic parameters, in which it is manifested, and to identify the pattern of nystagmic asymmetry and the stage of compensation of vestibular dysfunction. PMID- 2267690 TI - [Adoptive laser immunotherapy and photodynamic therapy in ORL oncology]. AB - Present-day developments in oncological applications of laser therapy are adaptive laser immunotherapy (ALIT) and photodynamic therapy (PDT). ALIT (helium neon laser) was used in 35 ENT-cancer patients to irradiate immunocompetent leukocytes isolated from blood in an Amino cell separator. The use of ALIT in the combined treatment of our patients improved their health condition. Cytological, immunochemical and immunological examinations of blood revealed an increased count of activated lymphocytes, normalization of acute-phase proteins, stimulation of cell-mediated immunity and nonspecific resistance. The pharmacokinetics and photodynamic activity of porphyrin compounds in mice with inoculated tumors were investigated. Experimental observations demonstrated that the application of photodynamic therapy of hematoporphyrins in ENT-oncology seems very promising. PMID- 2267692 TI - [Effects of earplugs on the development of hypoacusis and extra-aural pathology in workers exposed to industrial noise]. AB - Using an EC computer and Medstat-85 software, statistical multivariate analysis of data accumulated during 20 years of examinations of 210 workers of a textile (twisting) shop was performed. Out of these subjects 70 persons used antiphones (of ear plugs) continuously, 70 workers used them occasionally, and 70 subjects did not use them at all. It was found that hearing impairment and concomitant vascular disorders developed at an earlier stage and in a greater extent in those workers who never used ear plugs. The noise-induced changes proved more expressed than age-related vascular pathology. PMID- 2267693 TI - [Use of shortened latent auditory evoked potentials in the evaluation of the effectiveness of hearing aids]. AB - An electrophysiological correlate of an effective enhancement of hearing aids (HA) can be emergence of a well differentiated V wave in three BERA tracings. The presence or absence of an unstable V wave is indicative of an inadequate HA enhancement; when comfortable loudness is exceeded, high-amplitude V wave with a shortened latent period (LP) as well as other waves that do not belong to BERA are recorded. An average LP value of V wave for different types of hypoacusis has been determined when the HA output is set at comfortable loudness. Other factors that have an impact on the V wave LP are also considered. PMID- 2267694 TI - [Pathology of the upper respiratory tract as a manifestation of primary ciliary dyskinesia in children]. AB - This paper presents the results of examination of children with primary ciliary dyskinesia. It has been found that ENT pathologies form an obligate characteristic of this lesion. Primary ciliary dyskinesia can be reliably diagnosed with the aid special examination methods. Adequate treatment by an ENT doctor and a pulmonologist yields good results. PMID- 2267695 TI - [Diagnostic evaluation of meningeal syndrome in otogenic intracranial complications and infection]. AB - In 258 patients, neurological symptoms of otogenic leptomeningitis and diagnostic importance of the meningeal symptom-complex in the clinical development of other intracranial complications and sepsis were investigated. Otogenic leptomeningitis was characterized by the meningeal syndrome, rigidity of occipital muscles combined with Brudzinski's sign and Kernig's sign, albumin-cytologic dissociation in the cerebrospinal fluid, and, frequently, unilateral lesion of cranial nerves. Meningeal symptoms in the case of cerebrum and cerebellum abscesses did not always indicate leptomeningitis. Kernig's sign and its combination with occipital muscle rigidity can be an indication of cerebrum abscesses. With leptomeningitis and cerebrum abscesses, the rigidity of occipital muscles rarely occurs as a separate symptom, which emphasizes its importance in the topical diagnosis of subtentorial abscesses. PMID- 2267696 TI - [Diagnosis of glomus jugulare tumors]. PMID- 2267697 TI - [Topographic-anatomic bases of puncture biopsy of neoformations of deeply located parts of the parotid salivary gland]. AB - In order to ensure an adequate approach to the pharyngeal process of the parotid gland, we investigated interactions between anatomical structures of the face, jaws and neck, on the one hand, and deeply located compartments of the parotid salivary gland, on the other. We tested variants of intra- and extra-oral approach to puncture biopsy of the above compartments of the parotid salivary gland. We examined clinical and anatomical parallels of otorhinolaryngological symptoms in the case of tumor lesions of the gland. PMID- 2267698 TI - [Tomography of the pterygoid canals]. AB - This paper presents an X-ray scheme for calculating the depth of pterygoid canals required for accurate tomography. The scheme includes three lines: line A corresponds to the physiological horizontal line, line B is drawn, normally to line A through the tip of the nose, and line C is the perpendicular from line B to the upper third of the posterior wall of the pterygopalatine fossa. The length of line B plus 1 cm (thickness of external nose soft tissues) is the value to be determined. Twenty-six patients underwent X-ray examinations by an EDK-750B unit (70 kV, 150 mA, 1.65 s). In all cases 1-3 images were sufficient to obtain good visualization of the pterygoid canals. PMID- 2267699 TI - [Errors in the early diagnosis of malignant tumors of the ethmoid sinus]. AB - This paper discusses the factors responsible for delayed diagnosis of malignant tumors of ethmoidal sinuses. It presents 9 cases: keratinizing type (6 cases) and nonkeratinizing type (1 case) of squamous cell carcinoma, nasopharyngeal poorly differentiated carcinoma (1 case), esthesioneuroblastoma (1 case). The diagnosis was made on the basis of a detailed study of case histories (spontaneous nasal bleeding and recurrent polyposis) and X-raying (total, contrast and tomographic). The clinical investigation was supplemented with operational green filter optics that helped detect tumor specific lesions. The final diagnosis was made on the basis of histological examinations. PMID- 2267701 TI - [Methods of intranasal vibromassage]. AB - The advantages of the method of endonasal vibromassage with air pressure oscillations (at 10-12 Hz and 24-30 mm Hg) are: lack of injuries, lack of pain, and simultaneous effect on all nasal and nasopharyngeal structures. The application of endonasal vibropneumomassage in patients with vasomotor rhinitis proved effective in the case of the nervous form of the disease lasting for no longer than a year. PMID- 2267700 TI - [Use of porous permeable titanium nickelide implants in surgery of the frontal and maxillary sinuses (a clinical-experimental study)]. AB - The purpose of the investigation was to study the efficacy of closing the bone defect in facial walls of the frontal and maxillary sinuses, formed as a result of their purulent inflammation, by porous permeable titanium nickelide. Analysis of the experimental data (18 dogs) and clinical observations (20 patients in whom the anatomic structure and function of frontal and maxillary sinuses with osteomyelitis were restored by an antibiotic pooling implantation material) gives evidence that the material can be well used to reconstruct an organ with an infected wound. The porous structure of the bioinert graft facilitates the ingrowth of osteogenic tissues, which becomes packed in the bone matrix without any intermediate connective tissue layer. PMID- 2267702 TI - [Acoustic impedance measurement in the diagnosis of hypoacusis in children]. AB - In 1986-1988, we examined 1105 children no older than 15 years with various forms of hypoacusis. It was found that measurement of acoustic impedance can help topical diagnosis at any age, especially in children younger than 3 years. In 1988, we examined 350 children with conductive hypoacusis. The specific features of tympanography and acoustic reflexes allow early and accurate diagnosis of middle ear abnormalities. It is stressed that measurement of acoustic impedance may play an important role in examinations of patients with middle ear pathologies. PMID- 2267703 TI - [Case of bilateral laryngopneumocele]. PMID- 2267705 TI - [Simultaneous cases of nasopharyngeal cancer in mother and daughter]. PMID- 2267704 TI - [Air cyst of the pharynx]. PMID- 2267706 TI - [Limited idiopathic cholesteatoma of the external acoustic meatus]. PMID- 2267707 TI - [Foreign body in the tympanic cavity of a patient with chronic suppurative otitis]. PMID- 2267708 TI - [Leptomeningitis and multiple brain abscesses in acute otitis media]. PMID- 2267709 TI - [Experience in the use of extracorporeal correction of the immune system in the treatment of patients with LOR cancer]. AB - Correction of the immune status is one of the burning problems of current otorhinolaryngology. Recent developments in immunology allow interference at the cellular level. However, otorhinolaryngological practice is still based on oral, parenteral or local use of ineffective drugs. This paper presents early results of the application of extracorporeal cytapheresis combined with the modulator treatment of lymphocytes for the surgical therapy of 25 patient with ENT malignant neoformations of different stage and localization. Leukocytapheresis, i. e. separation of leukocytes, was performed by means of an Aminco (USA) or FK 3,5 (USSR) cell separator and the separated cells were treated with diuciphone. This method yielded good results as suggested by immunological, immunochemical, biophysical, and cytological measurements of blood. The method seems promising for ENT-cancer therapy. PMID- 2267710 TI - Equine topics. Cushioning the effects of anesthesia. PMID- 2267711 TI - A survey of caesarean operations on cattle in general veterinary practice. AB - The animal most frequently requiring operation for dystocia in this survey of 133 cases was the Friesian/Holstein heifer. In 38 per cent of cases the reason for surgery was an oversized calf and in 84 per cent the operation was performed on the farm of origin. The majority of the dams were operated on while standing, using a left flank incision, and under paravertebral or field infiltration with local anaesthetic solution. Exteriorisation of the uterus did not appear to be essential except when the calf was dead. Ninety-five per cent of the calves alive in utero and 91 per cent of the dams survived, although 30 per cent of the dams suffered ill-health afterwards. In nine cases neither dam nor calf survived. The fertility indices of those which were rebred were not markedly affected, but milk production was reduced by an estimated 12 per cent of the potential yield. PMID- 2267712 TI - Neoplasms of the apocrine sweat glands in 44 dogs and 10 cats. AB - Neoplasms of the apocrine sweat glands accounted for 2.0 per cent and 3.6 per cent, respectively, of all canine and feline skin neoplasms diagnosed during a period of three years. They occurred in dogs from six to 17 years of age of both sexes, and golden retrievers appeared to be predisposed; they occurred in cats from six to 17 years of age and there were no breed or sex predilections. In both species, the neoplasms were usually solitary and occurred anywhere on the body; they were nearly always carcinomas and histologically were usually of the solid type. There were no clinical measurements that made it possible to distinguish reliably between benign and malignant lesions. No distant metastases were recorded, even though 22.5 per cent of the canine carcinomas had invaded the lymphatic system. PMID- 2267713 TI - Influence of supplementary iron in late pregnancy on the performance of sows and litters. AB - On eight farms alternate sows and gilts within three weeks of their expected farrowing date were injected intramuscularly in the neck with 8 ml of an iron (gleptoferron) preparation containing 200 mg iron/ml, or kept as uninjected controls. Data from 513 iron-injected and 488 control animals were used in the analysis of results. Small, but not statistically significant, improvements were observed in the numbers of piglets born alive and dead/litter, the birth weights and weaning weights at three weeks, the numbers of piglets fostered on and off/litter, piglet mortality, the number weaned/litter and the weaning to service interval. The condition scores of the iron-injected sows were marginally below those of the controls at weaning, but their condition scores at farrowing had also been slightly below those of the controls. A summation of these trends would suggest an overall benefit of approximately 0.45 pigs/sow/year in favour of the iron-injected sows. PMID- 2267714 TI - Synchronised calvings after withdrawal of norgestomet implants from cows treated near term with prostaglandin. AB - To investigate whether calving could be controlled by the withdrawal of progestogen implants from cows treated near term with prostaglandin three cows (group 1) received an intramuscular injection of 5 mg flumethasone on day 270 of pregnancy, and four cows (group 2) and three cows (group 3) received implants containing 3 mg norgestomet in both ears on day 262 of gestation and were treated with a prostaglandin F2 alpha analogue on day 264. On day 270 the implants were removed and at the same time the cows of group 3 were treated with 5 mg flumethasone. Jugular blood samples were taken daily to estimate progesterone concentrations in the plasma. Luteolysis was achieved by the injection of prostaglandin, as judged by the decrease in plasma progesterone concentration in the cows of groups 2 and 3 on day 264. Pregnancy was maintained in these cows until after the removal of the norgestomet implants. The interval from the removal of the implants and, or, the injection of flumethasone on day 270 until the onset of second stage labour ranged from 36 to 47 hours and the mean intervals for the three groups were not significantly different. In all the cows except one from group 3 the dilatation of the cervix and vagina and the softening of the pelvic ligaments appeared normal at calving. It is concluded that calving near term can be synchronised by a progestogen in the absence of a corpus luteum. PMID- 2267715 TI - Pneumocystis carinii pneumonia in Danish piglets. PMID- 2267718 TI - Sudden death of Icelandic dairy cattle. PMID- 2267716 TI - Prevalence of scrapie in British flocks. PMID- 2267719 TI - Penetrating grass seed. PMID- 2267720 TI - Methods of spaying. PMID- 2267721 TI - Presumed anthrax in a camel. PMID- 2267722 TI - Treatment of Campylobacter in a bull. PMID- 2267723 TI - Age resistance to Theileria parva bovis infection in calves. AB - Data collected in the Zimbabwean province of Mashonaland-West, in the period 1980 1988, showed that mortality in calves owing to Theileria parva bovis infection (January disease) was significantly lower in animals younger than 7 months than in older cattle. Groups of seven Holstein-Friesian calves from non-immune dams aged approximately 1, 4, 7, 10 and 13 months were infected with a Theileria parva bovis tick-derived stabilate. The dose chosen was lethal for 40% of the calves in the trial. Mortality was highest in the 4-month age group. The reactions in the 7 , 10- and 13-month age groups became progressively milder. The reactions in the 1 month old calves were the least marked, being very mild. The age-related resistance in the youngest calves, as can be concluded from our results, is only of short duration and cannot explain the lower incidence of January disease observed in calves in the field. PMID- 2267724 TI - Countercurrent immunoelectrophoresis in the diagnosis of Taenia hydatigena cysticercosis in goats. AB - The procedure of countercurrent immunoelectrophoresis in the diagnosis of Taenia hydatigena cysticercosis in goats was carried out for antemortem diagnosis of T. hydatigena cysticercosis in experimentally and naturally infected goats. The antigens of cyst fluid, scolex and membrane of T. hydatigena metacestodes were purified and compared. The sensitivity of the test in experimentally and naturally infected goats was 57.1 and 52.5%, respectively, whereas its specificity using antisera raised against T. solium cysticercosis, hydatid cyst and Fasciola gigantica was 66.7 and 83.4% with partially purified and fractionated antigens, respectively. Of all three antigens, the cyst fluid antigen was found to be most reactive. The test could be employed for antemortem diagnosis of T. hydatigena cysticercosis using purified antigen. PMID- 2267725 TI - Mitochondrial NADH oxidase activity of Setaria cervi. AB - The bovine filarial parasite, Setaria cervi, has been found to contain NAD(P)H oxidase activity. The system was predominantly located in the mitochondrial membranes, with very little activity available in the soluble fraction of the organelle. The membrane preparation also exhibited the presence of a reduced pyridine nucleotide transhydrogenase which converted NADPH into NADH by transferring a hydride ion. The oxidase activity was inhibited by all the respiratory inhibitors examined, with the greatest sensitivity to rotenone, a site I-specific inhibitor. The system was also found to be susceptible to exposure to anthelmintics, amongst which levamisole proved the most effective. PMID- 2267726 TI - Grazing management strategies for the control of parasitic diseases in intensive sheep production systems. AB - The effect of forward (F) and lateral (L) creep grazing, as two possible management alternatives of intensive production systems, on the gastro-intestinal nematode epidemiology of ewes and lambs was studied. Two groups of Romanov x Rasa Aragonesa ewes rearing twins and maintained on an autumn-contaminated pasture at a mean stocking density of 35 ewes ha-1, were used. Measurements were made of the population of infective larvae on the pasture, level of serum pepsinogen, worm eggs in faeces of ewes and lambs, and lambs' growth rate. In addition, post mortem worm counts from 'indicator' lambs were used to establish the level of infection at each rotational grazing cycle. Two different waves of nematode infection were identified. In both treatments, the over-wintering larvae were responsible for the first outbreak of parasitism which was particularly important for lambs on Treatment F. The second wave of infection apparently came up with several overlapped L3 generations and had different effects on the animals of each group. While early pasture contamination was suffered by the lambs of Treatment F, lambs on Treatment L were not seriously affected until the end of the third grazing cycle (end of May). The different grazing behaviour of lambs in both treatments appeared to be related to the outbreak of parasitism in lambs. The general pattern of liveweight gains was similar for both groups of animals. However, during the first 90 days on pasture lamb growth rate under Treatment L (193 g day-1) was significantly higher than that under Treatment F (164 g day-1). The serum pepsinogen values, worm burdens and liveweight gains indicate that under intensive systems where lateral creep grazing is allowed for lambs, the level of parasite infection is maintained within acceptable limits for the first 90 days on pasture with lambs' growth rate close to their potential. However, the parasitic consequences of grazing under a forward creeping system indicate that anthelmintic drenchings should be used at lambing and at 3-week intervals thereafter during the first 42 days on pasture, after which the risk of contamination from the over-wintering population is over. PMID- 2267727 TI - Genetic control of immunity to gastrointestinal nematodes of cattle. AB - Previous studies have indicated that host genetics significantly affects the number of gastrointestinal nematode eggs per gram (epg) in the feces of calves during their first grazing season. An entire calf crop of approximately 190 animals was monitored monthly until weaning to verify these earlier results, and to begin to discern the basis for this phenomenon. A significant genetic effect on fecal epg values was not observed until calves had been on pasture for 2-3 months, and was demonstrable until late in the grazing season when the effect was lost. The loss of a genetic effect coincided with the appearance of significant numbers of the more highly fecund nematode species Haemonchus placei and Oesophagostomum radiatum, and with an apparent increase in Ostertagia ostertagi transmission, indicating that the observed genetic control of epg values may be species specific, dose dependent or both. Calves were selected from the population, and grouped according to their epg phenotype over the grazing season as either high or low epg calves. Postmortem examination of some of these calves indicated that worm burdens in the low epg calves were 60% of those of the high epg calves. Experimental challenge inoculation of the remaining calves indicated that: (1) challenge with Cooperia oncophora resulted in low epg calves harboring worm numbers that were 65% of those of high epg calves; (2) challenge with O. ostertagi resulted in similar numbers of worms in both groups, but the fecundity of worms in the low epg groups was significantly lower (P less than 0.05) than in the high epg group. Analysis of serum anti-Ostertagia antibody levels in the grazing calf population showed rises in serum IgG1, IgG2, IgM and IgA antibody levels during the grazing season. Peak serum IgG2 and IgG1 anti-Ostertagia antibody levels were found to be significantly affected by host genetic factors while IgA and IgM levels were not under such control. PMID- 2267728 TI - Efficacy of ivermectin delivered from an intraruminal sustained-release bolus against natural infestations of five African tick species on cattle. AB - The efficacy of ivermectin delivered by an orally administered prototype sustained-release bolus over approximately 90 days was evaluated against natural infestations of five African tick species. Twenty cattle, allocated by restricted randomization based on counts of standard Boophilus decoloratus, were allocated to two groups and were either given an ivermectin bolus or designated as non medicated controls. All cattle grazed a single pasture of native grasses for 20 40 days before treatment and until trial termination. Starting on Days 27, 40, 68 and 82 after bolus administration, four replicates were confined to individual tick-collection stanchions for 4 to 5-day periods. Ticks recovered from these cattle were counted by species, sex, and stage and degree of repletion; engorged females were weighed and incubated to determine the number which oviposited. For the other replicates, half-body counts of adult ticks (classified by species, sex and degree of repletion by females) were made at 1- and 2-week intervals through Day 90. Among replicates confined to stanchions periodically, fewer (P less than 0.05) engorged adult female B. decoloratus, Hyalomma spp., Rhipicephalus appendiculatus and Rhipicephalus evertsi evertsi were collected from bolus treated cattle than from controls. Numbers of engorged adult female Amblyomma hebraeum were reduced, but differences were not statistically significant (P greater than 0.10). Among cattle maintained continuously on pasture, tick numbers were reduced on the ivermectin-treated groups. A significant (P less than 0.05) treatment by linear time effect was seen for all adult ticks counted except R. appendiculatus. A significant (P less than 0.05) treatment by quadratic time effect was seen for A. hebraeum, B. decoloratus and R. evertsi evertsi, and overall treatment differences were significantly different (P less than 0.05) for these species. The differences tended to increase with time. Except for Boophilus, reductions in tick numbers on treated animals relative to controls were not readily apparent. There were no adverse reactions attributable to ivermectin treatment or the presence of the bolus. Each treated animal retained its bolus throughout the trial, based on metal detection. PMID- 2267729 TI - Parasites of livestock in Asir Province, southwestern Saudi Arabia. AB - Thirteen parasite species, three trematodes, five cestodes, one nematode, and four arthropods, have been reported in livestock in Asir, southwestern Saudi Arabia. The occurrence of Dicrocoelium dendriticum in imported sheep and Paramphistomum cervi in indigenous cattle is recorded for the first time in Saudi Arabia. PMID- 2267730 TI - Post-thawing viability of vaccines for bovine babesiosis and anaplasmosis cryopreserved with glycerol. AB - Live frozen vaccines containing Babesia bovis, Babesia bigemina or Anaplasma centrale were prepared using glycerol as cryoprotectant and stored in liquid nitrogen. The viability of the vaccines was tested inoculating calves 1 h (n = 12), 2 h (n = 12), 12 h (n = 6) and 24 h (n = 6) after thawing. Babesia bovis and A. centrale were detected in thin and/or thick blood smears in all vaccinated calves; however, 1 of 12 calves inoculated 1 h after thawing and 3 of 6 calves inoculated 24 h after thawing did not develop a B. bigemina parasitaemia. The longer post-thawing durability of frozen vaccines cryoprotected with glycerol compared with those cryoprotected with dimethyl sulfoxide, presented by other authors, will extend their use under field conditions. PMID- 2267731 TI - Anthelmintic activity of ivermectin against experimental Ascaridia galli infection in chickens. AB - The efficacy of ivermectin against Ascaridia galli infection was evaluated in chickens under controlled laboratory conditions in two separate experiments. In each experiment 22 White Leghorn chicks were randomly assigned to three groups of 10 (infected-treated), 9 (infected-control) and 3 (uninfected-control) birds. Each bird in the former two groups was orally infected with 1,500 embryonated A. galli eggs. The chicks in the treated group were subcutaneously injected with ivermectin at a dose of 0.3 mg kg-1 body weight on Day 10 (Experiment 1) and Day 35 post-infection (Experiment 2) for immature and adult infections, respectively. The treated birds had 0.9% (Experiment 1) and 0.4% (Experiment 2) worm recovery compared with 8.7 and 8% in the infected-untreated controls of the respective experiments. The fall in post-treatment faecal egg counts was 81 and 92% in birds treated on Days 10 and 35, respectively. The drug was found to be 90 and 95% effective against immature and adult worms, respectively. The lower lesion score and post-treatment near-normal haematobiochemical picture in treated birds confirmed these observations. The treated birds also had a better growth rate than the untreated chickens. The mature worms in the intestinal lumen of the host were more sensitive to the treatment than the immature stages of the parasite in the tissue phase. PMID- 2267732 TI - [Anticardiolipin antibodies in diffuse connective tissue diseases with IgG, IgM and IgA isotypes]. AB - Anticardiolipin (aCL) antibodies were assessed in isotypes IgG, IgM and IgA by the enzyme immunochemical technique in serum of 86 subjects with diffuse connective tissue affections and in 75 subjects of three control groups (syphilis, syndrome of common variable immunodeficiency and blood donors). In systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and syphilis the mean values of the three isotypes of aCL antibodies were significantly higher than in blood donors (p = 0.05 to 0.001); in diffuse scleroderma and primary polymyositis/dermatomyositis in isotype IgG (p = 0.01-0.001). Positive findings of aCL antibodies (isolated or in combinations of Ig isotypes (were found most frequently in SLE (34.4%), RA (33.3%) and syphilis (66.6%); sera of blood donors were positive in 8.7%. Venous thrombosis was recorded in the case-records of 28% patients with SLE but only in 5.4% of those with RA. Spontaneous abortion terminated 8/66 pregnancies in 28 women with SLE. In one female patient with SLE the aCL syndrome was detected. On account of frequent positivity of aCL antibodies in syphilis, the authors consider it essential to rule out the coincidence of this disease. Examination of aCL-IgA antibodies extends the detection of positive cases (isolated or in combinations of Ig) in SLE and RA. PMID- 2267733 TI - [Why are there anti-cardiolipin antibodies in patients with infectious mononucleosis and in patients with systemic lupus erythematosus?]. AB - The phenomenon of anticardiolipin antibodies (aCL) is in recent years the subject of interest as it is connected with manifestations of thromboses at different sites, with repeated miscarriages in pregnant women and with thrombocytopenia. As compared with the original finding in patients with systemic lupus erythematosus (SLE), the authors find they are present also in infection with the Epstein-Barr virus--in patients with acute infectious mononucleosis, in as many as 61% of a total number of 77 examined patients; in a group of 60 patients with SLE in 41% and in a group of healthy controls in 3.9%. aCL differ, however, as regards the distribution of isotypes--aCL of class IgM are found mainly in infectious mononucleosis, class IgG in patients with SLE. The authors discuss problems associated with the development and practical importance of these antibodies. PMID- 2267734 TI - [Possibilities of dialysis therapy in irreversible renal failure in rheumatoid arthritis with secondary amyloidosis]. AB - The authors discuss their initial experience with the treatment of secondary amyloidosis in rheumatoid arthritis with irreversible renal failure in patients included in a regular dialyzation programme. The hitherto assembled 15-month experience justifies the inclusion of patients with this cause of irreversible renal failure in a dialyzation programme. The reverse is not only wrong from the medical aspect but is inhuman and interferes with the life of families of these patients. Although the procedure during a regular dialyzation programme of these patients with rheumatoid arthritis with secondary amyloidosis is more complicated, more pretentious and more responsible, it is our medical duty to carry this burden together with the patient. PMID- 2267735 TI - [Levels of tetra-, triiodothyronine and thyroid stimulating hormone in patients with rheumatoid arthritis]. AB - The authors made in patients with confirmed or classical rheumatoid arthritis, using RIA, functional tests of the thyroid gland, i.e. tetra-, triiodothyronine and thyroid stimulating hormone. While deviations of tetraiodothyronine levels from normal very rare, a reduction of triiodothyronine was recorded in 50% and of TSH in 27.2%. Clinically manifest thyropathy, i.e. hyperthyroidism was found only in one female patient. The authors investigated changes in the values of the above tests in the course of rheumatoid arthritis and a dysbalance in the regulation of thyroid functions. The investigation comprises also a group of 18 subjects with rheumatoid arthritis where antibodies against the thyroid gland were assessed. The latter were elevated in two patients. PMID- 2267736 TI - [A 5-year study of cardiac involvement in polymyositis/dermatomyositis]. AB - Improvement of the diagnosis and new therapeutic opportunities revealed a number of organ affections also in patients with polymyositis and dermatomyositis. One of the prognostically important organ manifestations is affection of the heart. The prospective investigation comprises 15 patients with a confirmed diagnosis of polymyositis (10) or dermatomyositis (5). The investigation, using a number of non-invasive method (ECG, echocardiography, systolic time intervals, 99mTc pyrophosphate scan of the heart muscle), proved in the course of the 60-month investigation an increase of pathological findings from 40% at the onset (6/15) to 6 from 11 surviving patients (three died), i.e. a total of 64.3% of the group. Investigation of the fate of patients with signs of myocardial damage during the active stage of the disease (positive myocardial scan) indicates that in these patients also other signs of cardiac damage develop more frequently and that the general prognosis is more unfavourable. The authors consider therefore cardiac damage in the active stage of the disease a reason for intensive treatment. PMID- 2267737 TI - [Cytogenetic study in multiple myeloma. I. Chromosome findings in 56 patients]. AB - The authors submit the results of cytogenetic examination of 56 patients with multiple myeloma. Chromosome changes were found in 25, i.e. 45% patients. Structural changes were found most frequently in chromosomes no. 1, 11 and 14, numerical changes in chromosomes 3, 4, 9, 11, 14, 16, 19, 21, 22, X and Y. Marker chromosomes were present above all in hyperdiploid mitoses. The authors did not detect a relationship of chromosome changes and the type of produced monoclonal immunoglobulin, nor a statistically significant difference in the frequency of chromosomal changes in treated and untreated patients. Hyperploidy and complex rearrangements of chromosomes were observed mainly during progression of the disease. In three of four patients with developed secondary plasmocellular leukaemia the authors found a chromosomal change 14q+, in two as a result of translocation 11/14. PMID- 2267738 TI - [Cytogenetic study in multiple myeloma. II. Clinical significance of chromosomal changes]. AB - The authors evaluated in a group of 56 patients with multiple myeloma the clinical impact of assessed chromosomal changes. They found a close relationship between the frequency of chromosomal deviations and the extent and activity of the disease. The authors did not detect a relationship between the frequency of karyotypic changes and the number of plasmocytes in bone marrow nor a significant difference in the incidence of hypodiploidy in different immunochemical types of multiple myeloma. Patients with chromosomal changes had a reduced response to cytostatic treatment. The authors revealed a prognostic importance of chromosomal changes, in particular of hyperdiploidy and the concurrent incidence of numerical and structural deviations. The authors discuss the relationship of monosomia of the X chromosome and the Y chromosome to the clinical picture of the disease and chromosomal findings in secondary myeloblastic leukaemia, myelodysplastic syndrome and secondary plasmocellular leukaemia. PMID- 2267739 TI - [Validity of biochemical examinations in ascites in clinical practice]. AB - The authors examined, using biochemical, cultivation and cytological methods, ascites in 94 patients. They divided the patients into four groups: group 1 (36 patients)--malignant ascites, group 2 (35 patients)--cirrhotic ascites, group 3 (11 patients)--cardial ascites, group 4 (12 patients)--nephrogenic ascites. The authors tried to differentiate malignant ascites from non-malignant, based on biochemical parameters. As the composition of ascites is influenced by some factors (diuretics, dialysis) the authors recommend the use of biochemical analyses of ascites in clinical practice. PMID- 2267740 TI - [Side-effects of continuous and discontinuous cytapheresis]. AB - The authors evaluate the incidence of complications in 767 cytapreheses made on two types of blood cell separators. Complications, incl. technical problems before cytapheresis proper, were encountered more frequently during work with the discontinuous blood cell separators Haemonetics model 30 (27.%) than during work with the continuous automatic blood cell separator Fenwal CS 3000 (13.2%). Most frequently collapse and symptoms of hypocalcaemia were involved. Serious reactions account only for 7.6 and 4.4% of all reactions. The authors discuss the causes and possible prevention of complications during cytapheresis. With regard to the assessed results cytaprehesis by means of a separator can be considered a safe method in blood donors. PMID- 2267741 TI - [Is accurate dosing possible using infusion sets?]. AB - The authors discuss factors which influence the dispensing of infusion solutions by means of infusion sets regulated by a button. They draw attention to the fact that by means of infusion sets IS 103 and TS 203 accurate dispensing is not possible as the rate of flow changes markedly with the time of administration of the infusion. On the other hand, in the EXADROP dispenser marked slowing down of the infusion in relation of time does not occur and the authors recommend it therefore for common use in standard departments. PMID- 2267742 TI - [Microcirculation in the subcutaneous layer and in muscles in diabetes mellitus]. AB - The work is focused on the possibility of early diagnosis of diabetic microangiopathy. The authors used examination of microcirculation by the method of tissue clearance of Na 131I. In a group of 106 patients with diabetes thus the microcirculation of the lower extremities in the subcutaneous layer and the calf muscle was examined. A group of 36 healthy subjects served as control. An altered microcirculation was found in 75% type 1 diabetics and in all type 2 diabetics. In those with an altered microcirculation only in 23% type 1 diabetics and in 17% type 2 diabetics organ manifestations of diabetic microangiopathy (i.e. retinopathy and nephropathy) were lacking. It seems thus that altered Na 131I absorption in the lower extremities is an earlier sign of microangiopathic affection than identifiable organ changes. Examination of tissue clearance of Na 131I thus could reveal in time individuals threatened by this complication of diabetes. PMID- 2267743 TI - [Puncture biopsy of the joint--contribution to research on the joint milieu]. AB - The authors deal with articular needle biopsy with regard to the extension of knowledge and research of the articular environment. Articular biopsy is indicated in diseases associated with an articular exudate. It is made most frequently on the knee joint. In some diseases the histological picture of the articular lining is typical for the diagnosis, in some it is at least characteristic. In some instances an unequivocal interpretation of the histological finding is rather dubious from the diagnostic aspect. Needle biopsy of the joint is confronted with other findings and the clinical picture. Articular needle biopsy can be used for detection of therapeutic preparations administered systemically and in particular by the intraarticular route. Articular needle biopsy extends moreover the criteria used to evaluate the therapeutic effect. PMID- 2267744 TI - [Suggestions for criteria for uniform evaluation of changes in the spine in vertebral dysostosis of the Scheuermann type]. AB - The author recommends in his proposal of uniform criteria to evaluate pathological changes of the spine according to a pattern where the first place is held by morphological changes (unevenness of the covering plates, changes in the shape of bodies of the vertebrae, changes in the height of disc and changes in the curvature of the spine). The second place in held by functional changes and the third one by the general extent and quality of pathological changes. In the latter group the author draws attention to the appearance of a stigmatized spine. It is essentially an abortive form of vertebral dysostosis with frust not very marked morphological symptoms. He draws attention to the importance of this form for explanation of an obscure vertebral algic syndrome, in particular in children. The unform evaluation of these pathological changes should help to establish order in the hitherto controversial problem of evaluation of vertebral dysostosis. PMID- 2267745 TI - [Aspects of treatment of hypertension in rheumatic diseases]. AB - The author deals with the reasons of the frequent incidence of hypertension in rheumatic diseases and some special aspects of its therapy (nephrogenic hypertension in systemic diseases, weakening of the action of antihypertensive drugs by nonsteroidal antiinflammatory drugs, chronic corticosteroid treatment and the unsuitability of some antihypertensive drugs in different rheumatic diseases). PMID- 2267746 TI - [Use of nonparametric methods in medicine. VI. Evaluation using dependence by rank]. AB - The authors deal with the evaluation of dependence between two quantitative variables. They analyze Spearman's and Kendall's rank correlation coefficients. The procedure is explained on examples. Decision taking between the zero and alternative hypothesis is made possible by the enclosed tables of critical values. When the number of data is higher than 30, the significance of the two coefficients can be evaluated by means of the testing characteristic with a normal distribution. PMID- 2267747 TI - [The current problems of medicine in catastrophes in the USSR]. PMID- 2267748 TI - [The International Association of Emergency and Disaster Medicine, its origin, current state and the directions for its activities in the future]. PMID- 2267749 TI - [The interaction of civilian public health and military medicine in mass catastrophes]. PMID- 2267750 TI - [The Soviet and International Red Cross in natural disasters and catastrophes]. PMID- 2267751 TI - [The role of international Red Cross and Red Crescent societies in coordinating international help in emergency situations]. PMID- 2267752 TI - [The medical infrastructures in the case of natural disasters]. PMID- 2267753 TI - [The military medical service in emergency situations in peacetime]. PMID- 2267754 TI - [Children and earthquakes]. PMID- 2267755 TI - [Medical care for children in mass casualties]. PMID- 2267756 TI - [The problems of organizing prophylactic and epidemic control measures in crisis situations]. PMID- 2267757 TI - [Communication, organization and international help in natural disasters]. PMID- 2267758 TI - [The principles of rendering medical care to the victims in a disaster zone and during evacuation]. PMID- 2267759 TI - [The problems of medical protection for the population in emergency situations]. PMID- 2267760 TI - [The potentials of the modern science of resuscitation for saving the lives of victims in mass catastrophes]. PMID- 2267761 TI - [The effect of prehospital measures on the outcome and the value of blood loss replacement in injuries]. PMID- 2267762 TI - [The organization of medical care in technological chemical catastrophes]. PMID- 2267763 TI - [The organization of medical care for the victims of railroad crashes and accidents]. PMID- 2267764 TI - [Antishock and anesthesiological care in catastrophes]. PMID- 2267765 TI - [The modern concepts of the organization of medical care in multiple trauma]. PMID- 2267766 TI - [The surgical aspects of delivering specialized medical care to the victims of natural disasters and catastrophes]. PMID- 2267767 TI - [The neurosurgical aspects in disaster medicine]. PMID- 2267768 TI - [Burns--a problem in disaster medicine]. PMID- 2267769 TI - [The organization and procedures for specialized care in mass poisonings]. PMID- 2267770 TI - [The role of specialized centers in toxicological catastrophes]. PMID- 2267771 TI - [The planning and activities of toxicology centers in mass casualties]. PMID- 2267772 TI - [Medical psychological care during and after natural disasters and catastrophes]. PMID- 2267773 TI - [The structural organization of the member viruses of the Baculoviridae family]. PMID- 2267774 TI - [Postvaccinal anti-influenza immunity and its determining factors]. PMID- 2267776 TI - [Changes in the protease activity in the lungs of mice infected with the influenza A virus]. AB - In uninfected animals, the level of protease and protease-inhibiting activities in the serum are in balance which is broken after influenza A virus infection. Most profound changes occur within the first few hours after infection. In 6 hours postinfection the amount of protease decreases both in the lungs and serum of the infected animals, and the protease-inhibiting activity increases. In the period of the highest accumulation of the infectious virus 2 days after infection, proteolytic activity also decreases, this decrease coinciding with that of the inhibiting activity. The third period of increased protease activity also coincides with amplification of infectious virus progeny and appears to be associated with consequences of virus infection and bacterial superinfection. PMID- 2267775 TI - [The heterogeneity of an influenza virus A population in its capacity to induce the synthesis of avid antibodies]. AB - Influenza A virus variants were found to be capable of inducing synthesis of avid antibodies when different species and lines of animals were immunized. CBA mice were the most convenient model permitting differentiation of "avidogenic" from "nonavidogenic" virus variants with a high degree of certainty. Recombinants may differ from parental viruses in their capacity to induce synthesis of avid antibody; with this, the transmission of only one gene (HA) from the "avidogenic" parent into the system of genes of A/PR/8/34 st in ensured a high "avidogenicity" of the recombinant. The "avidogenic" virus variants had a more marked protective effect than "nonavidogenic" ones. PMID- 2267777 TI - [The primary structure of the hemagglutinin gene of strain A/Riga/9977/86--a drift variant of influenza virus A(H3N2)]. AB - The hemagglutinin gene primary structure of influenza virus A/Riga/9977/86 (H3N2) belonging to the "Coen/84" antigenic subgroup was determined by primer sequencing. A comparative analysis confirmed that the reversions of amino acids in the late stages of the H3 influenza virus subtype antigenic drift became more frequent and the antigenic variants remained in epidemic circulation longer. The possible role of some mutations is discussed. PMID- 2267778 TI - [The characteristics of the hemagglutinin from persistent variants of the influenza virus A/Victoria/35/72 (H3N2)]. AB - Electrophoresis in polyacrylamide gel of the reference influenza A/Victoria/35/72 (H3N2) virus and its persisting variants (PV) showed that the PV isolated on the 158th day from the moment of persistence modelling (PV158) had mutation in the gene of hemagglutinin (HA). This mutation is manifested by incomplete HA synthesis at 40 degrees C and increase of mobility of the light HA subunit (HA2). Analysis of nucleotide sequence of the greater part of HA gene of PV158 virus revealed 5 nucleotide substitutions four of which were significant. Three substitutions were found in Hal: 219 (Ser----Phe), 220 (Arg----Gly), 226 (Leu--- Gln) and one in HA2: 156 (Thr----Asn). The importance of these mutations in the determination of the PV phenotype is discussed. PMID- 2267779 TI - [An analysis of the antigenic structure of the hemagglutinins from different strains of the influenza B virus by using monoclonal antibodies]. AB - A comparative immunological analysis of the antigenic composition of hemagglutinin (HA) of influenza B virus drift-variants isolated during 46 years was carried out using monoclonal antibodies (MAb) to HA of B/Oregon 5/80 virus in HI test and solid-phase enzyme immunoassay. The presence of type- and group specific antigenic determinants was demonstrated which agreed with our previous data obtained in studies with polyvalent sera. However, using Mab three more group-specific determinants were detected which characterize HA of influenza B viruses isolated in 1970-1979, 1970-1984, and 1970-1986. PMID- 2267780 TI - [A diagnostic immunoblot for determining antibodies to the human immunodeficiency virus by using gradient polyacrylamide gel]. PMID- 2267781 TI - [The isolation and characteristics of recombinant monoclonal antibodies to the Lassa virus]. AB - Recombinant monoclonal antibodies to Lassa virus were produced. The reactivity of the monoclonal antibodies was studied by indirect fluorescence antibody (IFA) technique, enzyme-linked immunosorbent assay (ELISA), and radioimmunoprecipitation method. The observed reactivity did not correlate with IgG isotyping groups. PMID- 2267782 TI - [A virulence study of tick-borne encephalitis virus strains isolated in the southern Soviet Far East]. AB - Study of virulence for white mice and Syrian hamsters of 115 tick-borne encephalitis virus strains isolated in Maritime Territory showed virulence to be a complex biological manifestation of pathogenic properties of tick-borne encephalitis virus. The virulent properties of strains may have individual manifestations in each species of specific causative agent hosts and susceptible experimental biological models. PMID- 2267783 TI - [The persistence of the causative agent of amyotrophic leukospongiosis and the astrocyte reaction in monolayer cultures of brain cells]. AB - The amyotrophic leukospongiosis (AL) agent which is considered to be an unconventional virus was shown to replicate and amplify in non-neuronal monolayer brain cell cultures. The AL agent persistence was accompanied by complicated morphofunctional changes in astrocytes, some of them developing a specific cytodystrophic process. Phagocytosis in the infected astrocytes came to its end. The dose-dependent effect and selective sensitivity of these cells to the cytodestructive activity of AL was demonstrated. Astrocytes are regarded to be target cells serving as a reservoir for agent amplification. PMID- 2267784 TI - [The detection of a presumed fusion peptide comprising the surface glycoproteins of arenaviruses]. PMID- 2267785 TI - [The effect of inducers of endogenous interferon on the course of an autoimmune process in F1 inbred NZB/NZW mice]. PMID- 2267786 TI - [The effect of the procedure for sampling clinical material on the detection of influenza virus antigens by immunochemical methods]. PMID- 2267787 TI - [The growth-stimulating activity of Soviet-produced sera from different species of animals]. PMID- 2267788 TI - [The effectiveness of a solid-phase immunoenzyme system for the diagnosis of tick borne encephalitis]. PMID- 2267789 TI - [The quantitative determination of bovine serum albumin in preparations of measles and mumps vaccines by an immunoenzyme method]. PMID- 2267790 TI - [Hypermutation of the measles virus gene and persistent infection]. PMID- 2267791 TI - [Errors in the diagnosis of chronic intrahepatic cholestasis]. AB - In nine out of ten patients referred in the years 1982-1987 to the Infectious Diseases Department of the Medical Academy in Bydgoszcz with the diagnosis of chronic (sometimes lasting several years) intrahepatic cholestasis an extrahepatic etiology of cholestasis was recognised. The main causes of the made errors were, it seems, an excessive confidence in the results of laboratory examinations carried out by modern diagnostic methods and a not very careful analysis of the disease. Exploratory laparotomy should be the examination of decisive importance in cholestasis of unclear etiology. PMID- 2267792 TI - [Herpetiform dermatitis and atopic dermatitis]. AB - History data and clinical pattern were analysed in 33 children with herpetiform dermatitis (DH) and in 34 children with atopic dermatitis (DA). The differences are stressed between DH and DA as which it is frequently misdiagnosed, which is the cause of delayed treatment in DH (in the studied group 2.8 years on the average). The development of skin changes with accompanying itching in a child at preschool age should suggest the supposition of DH. PMID- 2267793 TI - [Epidemiology and treatment of purulent meningitis in children]. AB - The results are reported of the treatment of purulent meningitis in the years 1980-1987. The treated group comprised of 49 children aged from 2 months to 4 years. The most frequent cause was meningococcal infection. All children recovered, only in 6 youngest ones subdural hygroma remained and was emptied by punctures. The treatment included penicillin and sulphonamides, in normally used doses. Frequent lumbar taps were avoided since they traumatize the meninges. The treatment was continued 3 days after temperature fall. It was observed that bacteria attacked already in the perinatal period the damaged brain tissue. PMID- 2267794 TI - [Prevalence of ascariasis and giardiasis in children from 0 to 3 years old hospitalized in the years 1980-1984 and in 1987]. AB - The studies were carried out for six years (1980 - 1984 and in 1987) considering the frequency of invasion by A. lumbricoides and G. intestinalis in various years depending on age and sex. The clinical material involved 5948 children of either sex aged from 0 to 3 years. Ascariasis was found in 123 children (2.06%) and giardiasis in 54 cases (0.9%). The infestation was more frequent in boys and it was associated always with other diseases. PMID- 2267795 TI - [Preparation of health service personnel for widespread use of breast feeding--a pilot study. Part III--Practice and declared contraindications to breast feeding]. AB - The purpose of the study was a trial to find out in what degree the activities and suggestions of health service personnel with respect to pregnant women and lactating mothers might be an obstacle in beginning and maintaining of lactation. A high percent of studied personnel declared activities incompatible with a successful course of lactation and excessive extension of indications to artificial feeding of infants. A general direction was established for intervention within the framework of the programme of activities for breast feeding. PMID- 2267796 TI - [Comprehensive assessment of cell mediated immunity in petrochemical industry workers]. AB - In the group of 29 workers of Acetobenzene Division of the petrochemical plant in Ptock with occupational exposure to toluene, acetone, and ammonia a set of tests were done evaluating the state of cell-mediated immunity which made possible finding out persons showing abnormalities in the studied parameters. It is suggested to follow-up these person continuously with control immunological testing once a year. PMID- 2267798 TI - [Ileus caused by right sided paraduodenal hernia]. AB - A case is presented of an ileus caused by right-sided paraduodenal hernia. The result of surgical treatment was successful. PMID- 2267797 TI - [Problems in health services in the opinion of the public]. AB - Certain results are presented of a representative study of the public opinion on health service functioning in the City of Szczecin. The public opinion was favouring: 1) supplementation of the public health service with alternative health care, 2) partial covering of the expenses for drugs, 3) increased salaries for doctors and nurses, 4) partial payment for medical services. PMID- 2267799 TI - [Acute renal failure in a child with fulminant purpura]. PMID- 2267800 TI - [Plasma cell leukemia in a 65 year old patient]. PMID- 2267801 TI - [Surgical removal of a giant intracranial tumor (medulloblastoma) in a child- patient's chances and surgical problems]. AB - A case is presented of an 8-year-old child reoperated on for recurrence of intracranial expansive lesion. Intraoperative cardiac arrest occurred and resuscitation was unsuccessful. The authors analysed the supposed causes of failures and laid stress on problems which may be encountered by the anaesthesiology-neurosurgical team. A number of physiopathological processes occurring here are presented in mathematical form. PMID- 2267802 TI - [Two cases of cutaneous tuberculosis]. AB - Two cases of skin tuberculosis are reported. In one of them diagnostic difficulties were present, in the other pulmonary tuberculosis was associated with two forms of skin tuberculosis. Spinocellular carcinoma developed in a recently developed scar after invasive skin tuberculosis. PMID- 2267803 TI - Conceptions and misconceptions of the menstrual cycle. AB - Eighty college women were queried about their knowledge of three aspects of the menstrual cycle (menstruation, ovulation, and menopause). Questions concerned the biology of each event and the physical, emotional, and cognitive changes believed to be associated with them. Reasoning from the biases and limitations in the scientific and popular literature, it was predicted that: (1) women would be relatively uninformed about the menstrual cycle, but more informed about menstruation than about ovulation or menopause, and (2) negatively valued changes would be described more frequently than positively valued ones. Results indicated that basic knowledge of the menstrual cycle, even among well-educated women, is at times incorrect, generally incomplete, and negatively biased. These findings confirm the need for a more comprehensive approach to menstrual education that speaks both to the biology of the menstrual cycle and to norms and variability of associated physical and behavioral changes. PMID- 2267804 TI - Congenital disability and medical research: the development of amniocentesis. AB - The action imperative inherent in amniocentesis, one that emphasizes the detection and selective abortion of disabled fetuses, exerts a powerful influence on women's decisions to undergo prenatal diagnosis. In this paper, the construction of this imperative is considered through an examination of medical research that contributed to the development and clinical practice of amniocentesis. It is argued that this research reflects medical judgments about socially "undesirable" human attributes, professional interests, and individual, technical solutions to the "burden" of congenital disability. The necessity to consider the implications of this technology within both a feminist and disability rights framework is discussed. PMID- 2267805 TI - "Prostitutes as pariah in the age of AIDS": a content analysis of coverage of women prostitutes in The New York Times and the Washington Post September 1985 April 1988. AB - Misrepresentation in the media portrays women prostitutes as sexual transmitters of AIDS to men. Yet careful study of the available data shows male-to-female transmission of the HIV virus is the overwhelming mode of heterosexual transmission of AIDS. Content analysis is performed to analyze the role newspaper coverage played from 1985 through early 1988 in the social construction of prostitutes as a new target group for AIDS. The results show little concern for the health of prostitutes at risk for AIDS, but rather for their role as possible disease vectors. That women prostitutes were eagerly singled out as a target group despite a dearth of evidence points in large measure to their precarious position in society. And it highlights the impact media has when it acts as an uncritical sounding-board for government and medical press releases about a disease with dire social as well as physical consequences. PMID- 2267806 TI - Perceived barriers to exercise and weight control practices in community women. AB - A sample of community women was surveyed to determine exercise habits, weight control methods, and perceived barriers to sustaining and initiating exercise and weight management programs. Lack of time was reported to be the most significant factor limiting exercise, while lack of willpower and time constraints were the most frequently reported obstacles to weight management. Suggestions to aid adherence to exercise and weight control programs among women are outlined. PMID- 2267807 TI - Relationships between teenage smoking and attitudes toward women's rights, sex roles, marriage, sex and family. AB - This study analyzes the relationships of cigarette smoking to attitudes toward equal opportunities for women, attitudes toward appropriate roles for women and men, and attitudes toward marriage, sex and family. Our analyses utilize data for white high school seniors from the 1985 Monitoring the Future national survey. Smoking was not related to attitudes toward equal opportunities for women, attitudes toward sex roles, or attitudes concerning the parental role. However, students who had favorable attitudes toward cohabitation by unmarried couples and unfavorable attitudes toward marriage were more likely to smoke than students who had more traditional attitudes toward sex and marriage. The association between smoking and non-traditional attitudes toward sex and marriage was observed for both females and males. Additional findings suggest that rejection of conventional values and acceptance of deviance contribute both to non-traditional attitudes toward sex and marriage and to teenage smoking, and this is one reason why non-traditional attitudes toward sex and marriage are associated with smoking. PMID- 2267808 TI - Older women's health and financial vulnerability: implications of the Medicare benefit structure. AB - Elderly women and men have different patterns of disease and utilize health services differently. This essay examines the extent to which Medicare covers the specific conditions and services associated with women and men. Elderly women experience higher rates of poverty than elderly men; consequently, elderly women are especially likely to be unable to pay high out-of-pocket costs for health care. Using a new method for simulating out-of-pocket costs, the Illness Episode Approach, the essay shows that Medicare provides better coverage for illnesses which predominate among men than for those which predominate among women. In addition, women on Medicare who supplement their basic coverage by purchasing a typical private insurance "Medigap" policy do not receive as much of an advantage from their purchases as do men. The calculations also show that the Medicare Catastrophic Coverage Act would have had little impact on the gender gap in financial vulnerability. PMID- 2267810 TI - Motherhood lost: cultural dimensions of miscarriage and stillbirth in America. AB - Despite the frequency of incompleted pregnancies (an estimated 20-30% of all pregnancies), a veil of silence surrounds pregnancy loss in our culture. In the last fifteen years organizations have sprung up throughout the United States which protest the cultural denial of perinatal loss and seek to define a miscarriage or stillbirth as a legitimate source of grief. Participants in support groups are for the most part members of the white middle class and cannot be taken to represent 'American society' but because they are organized and vocal, members of such groups hold the potential for significantly changing the way miscarriage and stillbirth are treated in American society. This article explores a number of recurrent themes observed among participants of pregnancy loss support groups: the angst of an incompleted rite of passage; the struggle for defining the embryo, fetus, or neonate as a 'child' and of oneself as a 'parent'; the search for and attribution of meaning to a seemingly unexplainable event; and the link between changing attitudes towards birth, death, and personhood. The impact of new technologies on the experience of pregnancy and consequentially on the experience of pregnancy loss is also explored. Most prior studies of pregnancy loss have been quantitative and have focused on the individual. The anthropological approach, with its emphasis on the cultural construction of meanings and special understanding of ritual process adds an important dimension to this area of research. PMID- 2267809 TI - Cardiovascular stress reactivity and mood during the menstrual cycle. AB - This study examined blood pressure and heart rate responses to a mental arithmetic task in a sample of 16 regularly menstruating women during the follicular (postmenstrual) and luteal (premenstrual) phases of their menstrual cycles. Self-reports of physical and psychological symptoms (mood) were obtained prior to testing. A control group of men was matched to the women with regard to age and yoked to the women's cycle phases. Both women and men were told the study involved "phases of the moon" in order to eliminate subjects' awareness of participating in a biological cycle study. Consistent with prior studies that have eliminated women's awareness of taking part in a study on menstrual phases, no phase differences in mood were evident nor did the women's mood ratings differ from those of men's. In addition, there were no phase differences in blood pressure and heart rate reactivity. These findings suggest that hormonal variations characteristic of the luteal and follicular phases do not assert an influence on common assessments of cardiovascular stress reactivity. PMID- 2267811 TI - Gender roles, medical practice roles, and ob-gyn career choice: a longitudinal study. AB - This paper discusses follow-up data from physicians who were studied ten years earlier when they were medical students. Seventeen physicians were practicing ob gyn, and 57 of the physicians studied had been interested in an ob-gyn career when they were medical students. At Time 1, women were more likely than men to be strongly interested in ob-gyn, but they were no more likely than men to be ob-gyn physicians at Time 2. The desire to have a surgical specialty was much more important to men than to women practitioners. Men ob-gyn practitioners were significantly more traditional in their sex-role outlook as medical students than were either women practitioners or women who had been strongly interested in the field but did not enter it. The data suggest that women ob-gyn physicians are more likely than their male peers to be egalitarian in their relationships with female patients. PMID- 2267812 TI - [Epileptic syndromes of infancy and early childhood]. PMID- 2267813 TI - [Psychiatric disorders in epilepsy--1: Psychiatric classification]. PMID- 2267814 TI - [Psychiatric disorders in epilepsy--2: Results of clinico-psychologic studies]. PMID- 2267815 TI - [Drug resistance in epilepsy]. PMID- 2267816 TI - [Indications and inventory of methods for assessing psychological capacity of adolescent epileptics]. PMID- 2267817 TI - [Social considerations and results of rehabilitation in the long-term management of adult patients with epilepsy]. PMID- 2267818 TI - [School and occupational achievement of children and adolescents with epilepsy]. PMID- 2267819 TI - [Carl Reinhold August Wunderlich (1815-1877)--an important clinician of the 19th century]. PMID- 2267820 TI - [The overall medical problem of AIDS]. PMID- 2267821 TI - [HIV-associated infections]. PMID- 2267822 TI - [HIV-associated liver-and biliary tract diseases]. PMID- 2267823 TI - [HIV-associated infections and their diagnostic problems]. PMID- 2267824 TI - [HIV-infection in children]. PMID- 2267825 TI - [Cutaneous manifestations in HIV-infection]. PMID- 2267826 TI - [AIDS and ophthalmology]. PMID- 2267827 TI - [Demonstration of causative agent and antibodies: diagnostic significance and prognostic importance]. PMID- 2267829 TI - [Diagnosis and therapy of oral manifestations in HIV infection]. PMID- 2267828 TI - [Prevention and therapy of HIV-infection, current status and perspectives]. PMID- 2267830 TI - [AIDS as a nosocomial infection]. PMID- 2267831 TI - [Health and psychosocial factors at the workplace]. PMID- 2267832 TI - [Psychosocial factors at the work site and health--introduction]. AB - Basing on the definition of psychosocial factors at work places reasons for the increasing importance of these problems were explained. A theoretical frame work was represented as basis for interdisziplinary work consisting of an expanded load-strain-concept with stress-theoretical aspects. Various possibilities were discussed for the health promotion at work places. PMID- 2267833 TI - [Personal variables and their effects on physiologic stress reactions]. AB - In 24 male medical students hormonal, cardiovascular and state of mood data were collected on the day of an oral examination as compared to a control day. Analyses included 24-hour-noradrenaline-, adrenaline- and cortisol-excretion, blood levels of free testosterone, heart rate and blood pressure readings and state of mood ratings (Nitsch). Furthermore subdimensions of the type A construct, as included in the need-for-control questionnaire (Siegrist), were determined. Four subgroups were established according to total amount and stress reactivity of noradrenaline (NA) excretion. Further analysis showed that this line of separation held for the remaining hormones as well, thus revealing rather homogenous group- inherent hormonal patterns. However, in both groups with low hormonal stress reactivity cardiovascular reactivity was higher than in the groups with a pronounced hormonal stress response. Blood pressure rose highest and recovered slowest in the group, who had the highest NA and cortisol excretion on control day and highest allover cortisol excretion. This group rated high in the Siegrist subdimension "task-involvement" (inability to withdraw), the difference to the remaining groups being statistically significant. Neither the amount of hormonal nor that of cardiovascular reactivity were related to the state of mood ratings. PMID- 2267834 TI - [Task specificity and reproducibility of the psychophysiologic reaction pattern]. AB - This paper presents results from investigations of physiological activation processes concerning two subjects. Firstly: Different tasks cause different reactions of the activation variables. In our experiment the heart rate raised stronger in the mental arithmetic task than in the trakking task. Conversely, blood pressure and respiratory frequency showed higher values in the tracking task. Secondly: By analyzing the stabilities for repeated investigations we obtained the following results: a) The reliability of the physiological strain variables is higher than that of the difference values. b) Habitual values are predicted best by the second investigation. c) If the experiment is often repeated, one can determine intraindividual correlations between activation variables for every single person. PMID- 2267835 TI - Individual differences in adrenaline/noradrenaline reactivity and self-perceived health status. AB - The excretion rate of adrenaline and noradrenaline in urine was tested at 168 male workers of various professions at the age of 20 years up to 60 years, during daily work and on a free Sunday. It has been shown that adrenaline and noradrenaline excretion rates increase with age. The differential reactivity of adrenaline and of noradrenaline are not related to age. The differential reactivity of adrenaline, but not noradrenaline is related to the self-reported health status of the subject, measured several weeks before the field study itself. It is not related to absenteeism. In special studies on busdrivers a differential reactivity in adrenaline was found with respect to absenteeism. The results of the present study indicate, that this effect is probably accounted for by the component of health and wellbeing that is incorporated in the absenteeism figures. PMID- 2267836 TI - [From prevention to health promotion by job design]. AB - The definition of health once again was extended from well-being to the competence necessary for a socially and economically active life. Thus prevention may not be limited on impairment and illness. Along with the interest in factors producing illness the interest in health entrancing factors should be intensified. Main issues of health entrancing job design are: (1) Essential approaches of prevention are to be reevaluated. Mainly the strain/stress approach should be replaced by the approach of coping actively with the demanding tasks. (2) The objectives of health entrancing job design are to be re-evaluated too. The task demands (job content) are of equal importance as the work conditions. Job design should be centred around the desired health entrancing task characteristics. (3) The corrective type of job design should be displaced by a prospective design of health entrancing tasks from the outset. A theoretically based limited set of task characteristics, defined in technological terms, proved to be valid for the design of tasks with desired efficient and health-entrancing characteristics. PMID- 2267837 TI - [Effort--a form of self-imposed stress]. AB - Effort is analyzed as a top-down process which is a feature of autonomous work procedures. A rise in effort may affect different aspects of efficiency in performance: (a) Increment in speed, (b) increment in accuracy, (c) shifts in difficulty level, (d) focus on central aspects of the task. A "law of diminishing returns" is postulated which calls for a balanced utilization of all options. In an experiment, subjects worked in a simulated office environment. The main independent variables were high-effort vs. low-effort instructions, and assignment vs. free choice of tasks. The subjects were also grouped according to their scores in an intelligence and an anxiety test. The results confirm the general expectation that a rise in effort may affect performance in terms of speed, accuracy, choice of difficulty level, and focus. However, the result vary considerably with experimental conditions and personality variables. Apparently, effort imposes a mental and emotional load which is best coped with by the low anxious and high intelligent. PMID- 2267838 TI - [Modifying factors of the relationship between stress at work and state of health]. AB - Resources, particularly social support and control have been shown to moderate the stress process in various studies. Low social support or low control lead to a higher impact of stressors on psychological and psychosomatic dysfunctioning. Various mechanisms are suggested how resources may have an impact on the stress process. PMID- 2267839 TI - [Assessment of current and long-term sequelae of stress in professional drivers]. PMID- 2267840 TI - [Effects of stress and strain on health status and traffic behavior in professional drivers]. AB - The paper is based on the expectation, that the short and middle term sequences of strain in connection with the job demands on professional motorists have an influence on the traffic safety. Increasing rush, higher pretensions on the carriers for instance just-in-time-production, 24-hours-service and the competition between the countries of the EEC raise the level of demands. New arrangements between the countries of the EEC allow longer shifts. In extreme cases 84 hours per week are possible. The aim of our examination consists in showing the real working-conditions of professional drivers and their effects on the attitude to car-driving and to get information on the psychosomatic state of the drivers. PMID- 2267841 TI - [Behavior of biochemical stress reactions in real professional performance of teachers in relation to age and occupational ability]. AB - In order to investigate the strain of teachers as persons with chiefly psychic load several hormonal parameters (ACTH, HGH, cortisol, catecholamines) and trace elements (zinc, copper) were measured at a teaching day as well as at a teaching free day. The different influences of age and reduced professional performance on the concentrations of the biochemical parameters were shown. It seems that the variation of release of catecholamines is the most important parameter for the diagnostic of strain in such professional load. PMID- 2267842 TI - [Psychological stress at work and health status of medical personnel]. PMID- 2267843 TI - [Psychophysiologic stress and strain of the dentist in general dental practice]. PMID- 2267844 TI - [Significance of the social network, especially the relationship to work, for psychiatric rehabilitation]. PMID- 2267845 TI - [Aspects of health psychology in vocational rehabilitation of teachers]. PMID- 2267846 TI - [Follow-up of patients with organic cerebral psychosyndrome after disablement]. AB - On the basis of a longitudinal study fifty-three patients were diagnosed, three times medically and psychologically, with reference to the neuralorganic psychosyndrome in a ten-year period. Of these patients thirty-five were disabled by neuropsychiatric and internistic illnesses. The study was concerned with the long-term process of the health and the performance of the patient. After early retirement, the subjectively experienced condition of the health of the patient improved, while the memory and fluid intelligence remained on a low level, without further worsening. After early retirement, a reorientation of subjective values took place within the patient. Thereby, the performance criteria of the patients became less improved, while the social criteria for life satisfaction and future orientation gained in significance. PMID- 2267847 TI - [Effects of early biologic and psychosocial risk factors on mental performance and disease-promoting behavior of adult medical patients]. AB - Early biological and social risks were related to measures of cognitive functioning and illness behaviour in adult patients. RESULTS: 1. Self-reported data on risks in early developmental stages are consistent with longitudinal data and theoretical assumptions. 2. Patients with biological risks show deficits in fluid abilities and signs of mild cerebral insufficiency. 3. Socially handicapped patients tend to coronary-prone behaviour and report more emotional strain while coping with complex problems. PMID- 2267848 TI - [Significance of occupational, health and life satisfaction in coping with rheumatic complaints]. AB - In a pilot study with a prospective study design we analyzed the interaction between disease modifying drugs and coping styles. We examined 45 inpatients with definite or classical rheumatoid arthritis at the beginning of disease modifying drug treatment and eight months later. In this paper we evaluate the role of health satisfaction in relation to an effective therapy. The results of the discriminant analyses between sufficient and non-sufficient persons show that a differential discrimination can be achieved with psychosocial variables, for example diseasecompetency and self-mobility. Finally, our results show that a disease modifying drug treatment in rheumatic diseases must be completed with psychosocial treatments. PMID- 2267849 TI - [Life stress events preceding illness episodes in multiple sclerosis and ulcerative colitis--a comparison]. AB - As to the prevention of somatic and psychosomatic diseases it should be tested, whether life-events are of interest to pathogenesis of disturbances like multiple sclerosis and ulcerative colitis. The social readjustment rating scale (Holmes, Rahe) was used and the life-change-unite-score of the groups of patients (n = 30) and a normal population was compared. Patients with m.s. and u.c. have a significant higher LCU-score than the normal group. Between the two diseases one can find no difference. PMID- 2267850 TI - [Psychophysiologic particularities in patients with functional syndromes]. AB - Patients with gastroenterological or cardiovascular functional syndromes (n = 109) were examined by means of an extensive psychological standardized diagnostic programme and psychological strain analysis was carried out under psychogenic stress in laboratory. The results were compared with healthy probands (n = 51) likewise examined. Patients with functional syndromes significantly discriminated of healthy probands by more psychosocial risk constellation under strain caused by more distress and in parameters of performance and in psychophysiological field in some strain variables (heart rate, blood pressure, acral vasomotricity) and their dynamics. PMID- 2267851 TI - [Assessment of sociodynamic parameters and critical life change events in functional epigastric syndromes within the scope of an epidemiologic study]. AB - In a rural district 187 patients with functional upper abdominal syndromes were examined in a neurological outpatient department by means of a clinical epidemiological questionnaire (46 parameters) and a modified life-event-inventory by Holmes and Rahe (56 items), expanded multidimensionally by subjective parameters of events. The epidemiological and stress-theoretical start of examination aimed at the result whether both methods in practice can help individually for a diagnostics fixed to therapy of psychosomatically sick persons. The representation of some results is limited to the sphere of work. One third of all patients mentioned conflicts in this field. Life-events belonging to the sphere of work with highly emotional filling by stress-experience were mentioned by the half of all patients. Both methods allow a more structured recording of the life-situation, of specific charges, of the individual kind of experience and a faster approach to the sphere of motivations, to problems of the development of such persons and their competencies to overcome these problems, as well as both methods allow an intelligibility of the genesis of this disease. PMID- 2267852 TI - [Cognitive structure and risk of myocardial infarct]. AB - In a psychophysiological experiment with 18 patients with cardiovascular disorders but without infarction we proved the influence of habituallized cognitive structures on reactivity under mental load. We used the concepts of different causal attribution (Explanatory style: Peterson and Seligman) and psychic regulation of activity and action (Activity style: Gunther). It can be shown that patients with pessimistic explanatory style as well as with diffuse psychic activity control show coronary-prone reaction patterns under load (indicators: cortisol and triglycerids in serum). PMID- 2267853 TI - [Type A behavior--a uniform construct?]. AB - Single dimensions of the Type-A-behaviour pattern and their contributions to the etiology and pathogenesis of cardiovascular and psychosomatic diseases are very often discussed. Our studies are concerned with the analysis of 40 blue collar workers and patients (40 patients with hyperuricemia, 36 psychotherapy patients) in definite groups of age. By item analysis and multivariate statistical procedures (variance, factor and discriminant analysis) we found an overlapping effect of psychosocial factors of work and on the other hand the influence of neurotic symptoms and behaviour patterns. PMID- 2267854 TI - [Organizational and personal resources of health promotion. Staying healthy despite or because of stress?]. AB - In the ongoing sociopolitical discussion of health promotion there is a shift from curative concepts to preventive concepts. In the context of the comprehensive and positive orientation to psychosocial health demanded by the World Health Organization the question of resources for the maintenance and promotion of health is gaining significance. In addition, issues pertaining to pathogenesis are making way for issues pertaining to salutogenesis: What personal (individual), social and organizational resources to enhance health and to cope with stress are available to individuals in demanding and stressful situations? Cognitive-emotional and instrumental coping patterns, greater control over one's work (decision latitude), and social support in the work and life domains are resources whose interactive effects call for further research. Precise answers to this question are of practical significance because they affect decisions about steps to be taken to promote intra- and extra-organizational health as well as job and organizational design approaches to maintain health. PMID- 2267855 TI - [Characteristics of the work site and their relevance for cardiovascular risk factors; consequences for prevention from an epidemiologic viewpoint]. AB - Although standard risk factors are clearly related to cardiovascular diseases; even taken together they account for about half of the incidence rates in prospective studies. Therefore psychosocial variables - among them work related characteristics - are of increasing significance for research and prevention in CHD. Thus, an enlarged version of the KARASEK-conception was studied in the GDR MONICA-Population, aged 25 to 64 years. Additional to the original Karasek questionnaire, the more "objective" work characteristics as well as the scale "Social Interaction at workplace" are implemented. Based on data of this study, the usefulness but also the limitations of the diversified Karasek conception (Job Demands, Decision Latitude, Social Interaction at work) are demonstrated. In spite of the relevance for smoking, blood pressure, cholesterol and overweight of the Karasek-model recommended also the objective work characteristics as well as other mediating variables should be taken into account. As a consequence from our results, the GDR-MONICA-center has started a research programme which uses a complex system of diagnostic methods, among them the following conceptions: - Health knowledge/Attitudes --Social support/social network variables --Vital exhaustion --Life events --mediating personality factors (Type-A behaviour pattern etc.) together with other lifestyle-related factors, for instance physical activity, nutrition and smoking habits. Results from this multifactorial and integrative MONICA-Psychosocial study can be expected in the near future. PMID- 2267856 TI - [Personality and health]. AB - There are several scientific approaches and types of contribution which suggest themselves in the personality-health interface: 1. Theoretical reflections on a level of abstraction akin to that of philosophy; 2. work drawing its inspiration from research investigating the normal functioning of man's "ability" or "competence to act"; 3. empirical research determining the psychological characteristics of healthy individuals (mostly on the basis of a criterion group comparison between healthy and sick individuals); 4. elaboration and empirical validation of personality sub-schemes (such as imparting meaning to life, sense of control); 5. independent health psychology approaches to theories of health, models of health behaviour, health-related personality models and personality traits as health-securing factors. What remains to be developed is a "differential health psychology of the concrete individual", which might the way for prophylactic health promotion oriented towards the norm of individuality. PMID- 2267857 TI - [Psychological prevention in occupational medicine]. PMID- 2267858 TI - [Patterns of psychosocial stress factors and health criteria]. AB - Derived from the principles of capacity and of need's realization in the load strain-coping-concept a 5-cluster result with parameters of subjective health and psychosocial factors is demonstrated. These patterns reflect the different connections between health and the person-environment interaction. A high subjective professional load is connected with a poor health state only in a low professional performance and/or deficits of need's realization. PMID- 2267859 TI - [Perioperative chemoprophylaxis in percutaneous nephrolitholapaxy]. AB - In 48 patients suffering from giant renal calculi a percutaneous nephrolitholapaxy was done. The use of perioperative antibiotic prophylaxis using aminoglycosides or cephalosporins was effective in reduction of postoperative urinary tract infections. PMID- 2267860 TI - [Metabolism and pathophysiology of oxalic acid]. AB - The pharmacokinetics and pathophysiology of oxalic acid in human organism are presented. In the formation of urinary calculi the level of urinary oxalic acid is important, but the knowledge of metabolism and various disturbances is the guide of a successful treatment and metaphylaxis. Therefore, the diagnostics is a prerequisite for successful dietetic and therapeutic measures as shown in absorptive hyperoxaluria. PMID- 2267861 TI - [Which studies are needed for the prediction of postoperative serum creatinine in unilateral nephrectomy? A retrospective analysis of 136 nephrectomies]. AB - Among 136 patients with unilateral nephrectomy between 1985 and 1988 at the Marienhospital Gelsenkirchen the renal function was evaluated in the postoperative course. The serum creatinine value did increase from 88.4 +/- 5.3 mumol/l preoperatively to 168.8 +/- 13.3 mumol/l on the 10th postoperative day. The elevation was significantly higher in patients with more than one associated disease (e.g. diabetes, hypertension). The extent of creatinine elevation could predicated safe by both preoperative creatinine value and isotope renal split function analysis. Therefore, functional isotope examination may not be indicated in patients without impairment of renal function. PMID- 2267862 TI - [Familial juvenile nephronophthisis--a genetically-caused kidney disease]. AB - It is reported on the course of the autosomal recessive transmitted familiar juvenile nephronophthisis in 3 siblings. Direct symptoms are polydipsia and polyuria with terminal course of chronic renal failure which could treated by dialysis and transplantation. Examination of the safe (parents) and possible (healthy siblings) heterozygotes was without particularities. PMID- 2267863 TI - [Effect of indomethacin on the vital prognosis and homeostasis of rats with kidney insufficiency]. AB - The medicamentous-therapeutic modulation of pathogenic hyperfiltration of residual nephrons by the prostaglandin synthesis inhibitor indomethacin was evaluated again. The experimental study of inbred wistar rats including a low indomethacin dosage of 1.5 mg/kg BW, a strong reduction of renal parenchyma (80%) and an increased food protein content of 40% did show the known results: indomethacin may impair the vital prognosis of severe renal injury. PMID- 2267864 TI - [Computer-assisted information processing in nephrology exemplified by the Nephrology-Dialysis Data System]. AB - The data system nephrology/dialysis (DSND) may improve the documentation and information processes used in chronic hemodialysis. DNSD is efficient if the data input is done carefully. It is possible to display large numbers of laboratory and dialysis data arranged alpha-numerically or graphically. Data over a period of 5 weeks or 14 consecutive examinations are recorded. An advantage is the possibility to print letters, labels and dialysis protocols. For scientific questions the points of class wideness for laboratory results, weight changes or medication are possible. Furthermore, the use of DSND may be valuable for use in a kidney transplantation information system. PMID- 2267865 TI - Renal hypertension in rats with hereditary polycystic kidney disease. AB - Hereditary polycystic kidney disease (PKD) was observed in a Han:SPRD rat mutant. Cysts were of tubular origin and occurrence was more pronounced in males than in females. In male rats polycystic kidney disease was associated with a marked elevation of systolic blood pressure. Therefore this rat mutant can be considered as a laboratory animal model for renal hypertension associated with adult polycystic kidney disease in man. PMID- 2267866 TI - [Orotracheal intubation in rats]. AB - A detailed description of the technique of orotracheal intubation under visual control in rats is given. This method was used successfully in 190 animals, the complication rate being 3.2%. The hazards consisted of laryngospasm (1.6%) and fatal bleeding (0.5%). Intubation was proved to be a safe, reliable, simple and atraumatic way to establish a patent airway in this laboratory animal. PMID- 2267867 TI - Heart transplantation in the rat: experience with a modified technique of heterotopic grafting. AB - Heart transplantation in the rat is a frequently used model to study immunological problems of primary, vascularized allografts. A modified technique of heterotopic grafting is described in detail. The donor heart is transplanted heterotopically into the recipient with the brachiocephalic artery anastomosed to the renal artery with 10 single sutures, and the pulmonary artery to the renal vein with 2 continuous, semicircular sutures which were left untied. Both anastomoses were done end-to-end with 10-0 Ethilon. The experience with 187 rat heart transplants are reported. The time needed for one transplantation ranged from 25 to 35 min (mean 30 min). Complications like bleeding, thrombosis and primary no-function did occur in 12 out of 187 transplants (6.4%). In conclusion, this modified technique of heterotopic heart transplantation in the rat is less time consuming and highly successful. PMID- 2267868 TI - Availability of solid feed and growth rates of pre-weaned mice of different litter size. AB - The effects of litter size and availability of solid feed before weaning on the growth mice were studied. Pups of small litters (n = 3) grew significantly faster than mice of large litters (n = 10), the mean difference at weaning being about 3 g. The difference in body mass persisted after weaning; at the age of 98 d the mean difference was about 5 g. Availability of solid feed to pre-weaned mice significantly stimulated mass gain of litters consisting of 10 but not of 3 pups. Body masses of the dams during the suckling period were markedly influenced by litter size: Mice with 10 pups had increased body masses when compared with mice having 3 young. By the time of weaning, body masses of mothers with larger or small litters had become similar again just as they were immediately after parturition. PMID- 2267869 TI - Cushing's syndrome- and disease-like lesions in rats. AB - Cushing's disease and Cushing's syndrome-like lesions were observed in four male rats. 2 revealed ACTH-positive pituitary tumours associated with bilateral adrenal cortical hyperplasia (case 1, 2). The other 2 rats had metastasizing adrenal cortical carcinomas with marked adrenal cortical atrophy of the opposite adrenal glands (case 3, 4). Pathological lesions observed varied between the animals and included "potbelly", severe obesity, fatty degeneration of the liver, atrophy of the pancreas and greater sublingual glands with fatty infiltration, testicular atrophy, ulcers of the forestomach and purulent inflammation in different organs. PMID- 2267870 TI - [Biochemical polymorphism in a dwarf goat population]. AB - Biochemical polymorphism of 116 dwarf goats has been studied by starch gel electrophoresis. The systems haemoglobin, ceruloplasmin and erythrocyte esterase were monomorphic. 4 loci were found to be polymorphic: amylase, transferrin, alkaline phosphatase, and albumin. The allele frequency of these traits was given. PMID- 2267871 TI - A method of intraduodenal administration of fluids to chickens. PMID- 2267872 TI - [Do tumor markers provide a diagnostic gain?]. PMID- 2267873 TI - [Fetal echocardiography. I: Methods, limitations and indications]. AB - The prenatal detection of congenital heart disease is rather seldom, compared with other fetal malformations. The paper considers the necessity of the development of fetal echocardiography and presents therefore an introduction for the prenatal sonographer. The fetal cardiac characteristics are first analysed, before considering the possibilities and frontiers of the investigation. The different available sonographic methods like the real-time, M-mode, pulsed Doppler and color Doppler are discussed and the importance of each one is emphasized. The indications for fetal echocardiography are further enumerated, as well as the possible consequences resulting from the diagnosis of a heart abnormality. Because of the sophisticated ultrasound devices needed for a precise diagnosis as well as the optimal postnatal care, suspected fetuses have to be referred to centers specialised in perinatal medicine. PMID- 2267874 TI - [Pelvimetry using computerized tomography. I. Theoretical and methodical fundamentals]. AB - The first part of our article deals with the basic aspects of using computed tomography in obstetrical pelvimetry. A macerated osseous female pelvis was used to measure the true conjugate, the transverse plane of the pelvic inlet, the interspinous line and the distance between the ischial tuberosities. The same pelvis was then examined computed tomographically. A lateral and a posterior anterior scan, and a single scan through the iliac spines were performed. The results of the direct measurement agreed highly with the values achieved computed tomographically if the phantom was positioned exactly on the mid-line of the examination-table, if not, the true conjugate was elongated. Measurements of the superficial and the intravaginal radiation dose in patients demonstrated a significantly lower risk in computed tomography than in conventional x-ray methods. We recommend computed tomography in obstetrics as a safe, accurate and reliable method. PMID- 2267875 TI - [Surgical possibilities in congenital abnormalities]. PMID- 2267876 TI - [Type and frequency of gynecological tumors in the Gondar region of Ethiopia]. AB - The present work was done to examine the type and frequency of benign and malignant gynecological tumors in patients treated during the 5 years period from 1982 to 1986 in the Gondar College of Medical Sciences. The different pathohistological findings were compared with the history and chief complaints of the patients. A total number of 208 patients with benign and of 93 patients with malignant tumors could be analyzed. In the group of benign tumors we observed most frequently breast tumors (25.5%), endometrial and cervical polyps (24.5%), and myoma uteri (23.1%). Patients with benign ovarian tumors were treated in 40 (19.2%) cases. In the group of malignant tumors we have seen breast carcinomas (31.2%) and cervical carcinomas (34.4%) most frequently followed by the endometrial (13.0%) and ovarian (11.8%) neoplasms. Comparison with the data of the literature has shown that the mean age of our patients is lower and the number of women with advanced carcinomas is higher than in other reports. PMID- 2267877 TI - [Bilateral fetal hydrothorax]. AB - A bilateral fetal hydrothorax was recognized in the second pregnancy of a 30-year old woman. Because of increasing pleural effusions, fetal hydrops and hydramnion a cesarean section was performed in the 31st week of pregnancy. The child died of pulmonary hypoplasia. The ante- and postnatal diagnosis and therapy and the poor prognosis of bilateral congenital hydrothorax are discussed. PMID- 2267878 TI - [Cerebral metastasis of a cervix carcinoma]. AB - We present our first case of cerebral metastasis from cervical carcinoma in a living patient after primary treatment of the tumor. The metastasis was surgically removed, with a bad outcome. The lack of guidelines for the treatment of this complication, which is due to its extremely low frequency, is discussed. PMID- 2267879 TI - [Should there be quality control in obstetrics or not?]. PMID- 2267880 TI - [Diagnosis of breast carcinoma: "Mammography and additive methods"]. AB - Review about diagnostic methods in breast cancer with special reference to mammography. Comparison about the accuracy of mammography, fine needle biopsy, clinical investigation, electron thermography and plate thermography. PMID- 2267882 TI - Follicular size and steroid secretion of dominant bovine follicles. AB - Twenty one estrogen-active bovine follicles obtained in the preovulatory period prior to the endogenous LH peak were superfused for 10h. Follicular diameter and superfusate estradiol (E2), testosterone (T) and progesterone (P4) were measured. A close correlation between follicle size and E2 secreted into the superfusate was found (r = 0.77; p less than 0.01). There was no correlation between superfusate T or P4 and follicular diameter. These data indicate that within certain limits the amount of E2 secreted can be predicted by follicle size in an in vitro superfusion system. As follicle size correlates closely with granulosa cell number in estrogen-active follicles, one can speculate that the rise in estrogen secretion is a reflection of an increase in granulosa cell number of the dominant bovine follicle. The application of these in vitro findings to the in vivo situation might help in the interpretation of the quality of ovarian stimulation with hMG/hCG. PMID- 2267881 TI - [In-vitro rates of fertilization and culture to blastocyst stage of mouse oocytes following co-incubation of murine spermatozoa with Escherichia coli and Ureaplasma urealyticum]. AB - Mouse-spermatozoa were released of the ductus deferens and coincubated with different strains of E. coli resp. U. urealyticum before inseminated with oocytes of superovulated female mice. Daily light microscopic observations of embryonic development took place. Coincubation of spermatozoa with bacteria concentration of 10(3) cfu/ml E. coli revealed no changes in fertilization or culture rates as compared to the uninfected control group. In the same way a coincubation with 10(6) cfu/ml had no influence on the fertilization rates in vitro, however the culture rates were considerably reduced. Only one strain of ureaplasma urealyticum effected after coincubation with spermatozoa a reduced fertilization rate, the embryonic development into blastocysts after in vitro fertilization of spermatozoa infected with ureaplasma urealyticum showed a marked reduction in all but two strains. PMID- 2267883 TI - [Importance of psychometric studies in gynecological tumor follow-up care]. AB - 100 patients successfully treated for gynecological tumors and 100 females who never had suffered from a malignant disease were investigated for neurosis by means of a special questionnaire according Hock and Hess. 52% out of the tumours patients and 42% of the control group demonstrated symptoms and signs of neurosis. The difference was not significant. Patients with tendency to depression or neurosis can be detected with psychometric methods and treated accordingly. PMID- 2267884 TI - [Struma ovarii, a rare ovarian tumor]. AB - Teratomas, which consist only or predominantly of thyroid tissue, are termed struma ovarii. Two cases are reported, where after previous strumectomy the histologic diagnosis was struma ovarii. Because of postoperative TSH-rise hormonal activity can be assumed. The proper diagnosis is seldomly made preoperatively, this could be done by abdominal scintigraphic imaging of radioiodine uptake in the tumour. PMID- 2267885 TI - [Macromastia in pregnancy--normal or a complication?]. AB - Pregnancy macromastia is a rare condition (1/100,000 pregnancies). It is reported on 2 cases of massive hypertrophy or gigantomastia over the past 25 years at Charite. The hypertrophy of connective tissue was histopathologically recorded from either case. The therapeutic approach is discussed with reference to literature. Conclusion are drown with regard to differential treatment of this rare clinical problem. PMID- 2267886 TI - [Chorangioma of the placenta]. AB - The authors describe a rare case of large tumour of the placenta (chorangioma) in a 25-year-old woman. The chorangioma was prenatally diagnosed by sonography in the 22nd gestational week. The course of pregnancy was not complicated. After sonographic observation of the course of the disease the woman was delivered of a child without malformations in the 39th gestational week. PMID- 2267887 TI - Migraine headache--a long-term approach. PMID- 2267888 TI - Morbillivirus infections of seals during the 1988 epidemic in the Bay of Heligoland: III. Transmission studies of cell culture-propagated phocine distemper virus in harbour seals (Phoca vitulina) and a grey seal (Halichoerus grypus): clinical, virological and serological results. AB - Eight harbour seals (Phoca vitulina), two of them seronegative, six seropositive against PDV and a seronegative grey seal (Halichoerus grypus) were exposed to a low doses of a cell culture-propagated phocine distemper virus isolate (PDV 2558/Han 88). An intranasal route of inoculation was chosen. Clinical signs, resembling those of 1988's seal disease and seroconversion were observed in both seronegative harbour seals. One of them succumbed to the infection. The virus was not transmitted to another susceptible harbour seal which served as in-contact animal. Virus could be recovered from leucocytes of the diseased seals. Viremia was also present in a seropositive harbour seal that developed mild clinical signs; other seropositive seals were protected from clinical disease. The grey seal showed seroconversion upon inoculation, but did not develop any signs of disease. The humoral immune response of the seals plainly discriminated between homologous (PDV) and heterologous (canine distemper virus, CDV) virus as shown by virus neutralization tests and an antibody-binding assay (PLA). PMID- 2267889 TI - IgG from cows with parturient paresis changes the thermodynamic behaviour of bovine erythrocyte acetylcholinesterase. AB - Parturient paresis affects about 10% of all cows. The most common treatment is injection of various Ca-salts and MgCl2 and about 80% recover after repeated injections. The effect of IgG on the Arrhenius plot of bovine erythrocyte AChE was studied. The plot was normal, i.e. biphasic (a broken line) in the presence of IgG from healthy cows. The highest concentration tested was 10 mg/ml. Before one injection of the Ca-Mg solution 5 mg/ml IgG from sera of paretic cows (n = 10) changed the Arrhenius plots to monophasic (linear). Thus, paretic cows have antibodies against AChE. After injection the change to linear plots was observed already with 1 mg/ml IgG. Apparently, the level of antibodies in serum affecting AChE increased about 5-fold. This is considered to be due to dissociation of bound antibodies from various AChEs. All cows recovered after one injection and release of AChE antibodies might be important for the recovery. Incubation of blood from paretic cows (n = 3) with Ca-salts and MgCl2 increased the amount of free AChE-antibodies about twofold; the Arrhenius plots became linear at 2.5 mg/ml IgG compared with 5 mg/ml before the incubation. This should be due to release from AChEs on blood corpuscles as erythrocytes and lymphocytes. But the increase of antibodies after incubation of blood does not account for the whole increase following the treatment of paretic cows. AChE antibodies are probably also dissociated from other sites, such as neuromuscular junctions. PMID- 2267890 TI - Detection of a novel chloramphenicol resistance plasmid from "equine" Staphylococcus sciuri. AB - A small chloramphenicol resistance (Cm) plasmid of 4.65 kB could be detected in an "equine" Staphylococcus sciuri-culture. This plasmid, designated as pSC3, was identified by interspecific protoplast transformation. On the basis of restriction endonuclease analyses a detailed restriction map of pSC3 could be constructed. This allowed structural comparisons of pSC3 with Cm-plasmids of other staphylococcal species from infections of humans and animals and identification of pSC3 as a member of the pC 221-family of staphylococcal Cm plasmids. The pSC3-plasmid encoded an inducible chloramphenicol acetyltransferase as confirmed by enzymatic assays. This enzyme could be demonstrated in cell-free lysates of Cm-induced pSC3-transformants. PMID- 2267891 TI - Demonstration of alpha and beta components of group B streptococcal protein antigen c in serum-soft agar. AB - Among 85 group B streptococcal cultures with protein type antigen c 56 cultures demonstrated a diffuse type of colony morphology in plain soft agar. The addition of monospecific antibodies against the protein antigen c components c alpha and c beta converted specifically the colony morphology from diffuse to compact. According to this results the serum-soft agar technique could also be used to further characterize individual cultures of group B streptococci with protein antigen c. PMID- 2267892 TI - [Adaptation of permanent bovine kidney cells to serum free hormone supplemented cell culture media]. AB - The examinations show, that it is possible to adapt MDBK-cells (ATCC CCL 22) to serum-poor (0.1% fetal calf serum) and to serum-free, adequate supplemented media. Morphology of the cells remained unchanged. The components of the serum free medium are a 50:50 mixture of Dulbecco's modified Eagle's medium and HAM's F12 medium, supplemented with insulin (5 micrograms ml-1), transferrin (10 micrograms ml-1), thyroglobulin (10 micrograms ml-1), prostaglandin E1 (50-100 ng ml-1). Seeding cells at a density of 26.10(3) cm-2 at day 0 resulted in better multiplication than a higher seeding density. PMID- 2267893 TI - Antibiogram of staphylococcal strains isolated from milk and milk-products. AB - A study of the resistance patterns of 248 staphylococcal isolates from milk and milk products to eight antimicrobial agents using the disc method showed that 80 (32.3%) were resistant to sulphafurazole, 75 (30.2%) to penicillin G, 63 (25.4%) to ampicillin, 23 (9.3%) to cloxacillin, 19 (7.7%) to tetracycline, 17 (6.9%) to streptomycin, 14 (5.6%) to erythromycin and 12 (4.8%) to chloramphenicol. One hundred and sixteen (46.8%) of the 248 staphylococcal isolates were sensitive to all the agents tested. A significant percentage (P less than 0.05) of the isolates from raw milk were resistant to erythromycin, sulphafurazole, cloxacillin, penicillin G and streptomycin compared to isolates from fermented milk. The minimum inhibitory concentrations (MIC) as determined by the tube method for isolates resistant by the disc method, were greater than or equal to 16 micrograms for ampicillin in 5 (11.9%) isolates; greater than or equal to 40 micrograms for cloxacillin, 9 (36.0%) and greater than or equal to 12 international units for penicillin G amongst 12 (22.2%) isolates. MIC values of greater than or equal to 40 micrograms were recorded for 9 (90.0%), 9 (69.2%), 8 (73.7%) and 7 (70.0%) isolates to chloramphenicol, streptomycin, erythromycin and tetracycline respectively. The relatively high level of resistance to antimicrobial agents is a reflection of misuse or abuse of these agents in the environment. PMID- 2267894 TI - [The detection of the pathogenicity of Listeria using permanent cell lines as an alternative for animal studies]. AB - Culture filtrates of 38 strains of Listeria (L.) monocytogenes and of 4 strains of L. ivanovii were all cytotoxic for the vero cell line. Culture filtrates from 35 strains of L. innocua, 12 strains of L. seeligeri, 5 strains of L. welshimeri and 4 strains of L. grayi showed no cytotoxicity for the continuous cell line vero. The use of continuous cell lines permits to distinguish between pathogenic and non-pathogenic Listeria strains and seems to be a suitable method to replace the mouse pathogenicity test or the fertilized hen's eggs test. PMID- 2267896 TI - [The treatment of cirrhosis and its complications]. PMID- 2267895 TI - In vitro activation of bovine macrophage and peripheral blood mononuclear cells by Nocardia rubra cell wall skeleton (N-CWS). AB - Nocardia rubra cell wall skeleton (N-CWS) was used for immunotherapy to bovine leukemia virus (BLV)-positive cattle with enlarged subcutaneous lymphatic nodules. Electron microscopical observations showed the infiltration of macrophage and T cells around N-CWS treated lesions. Antitumor effect induced by N-CWS was examined in vitro. The maximum cytolytic activity of macrophage was observed, when the cells were incubated with 10 micrograms/ml of N-CWS. Chemiluminescence response of peripheral blood mononuclear cells (PBMC) using N CWS as stimulant was observed with a high level of activity for a long period, 5 hr. Mitogenic effect of N-CWS to PBMC was observed in the presence of macrophages but not without macrophages. Furthermore, interleukin 2 activity was recognized in supernatant of PBMC cultured with N-CWS. Maximum cytotoxic T lymphocyte response was induced when PBMC were cultured with 0.1 micrograms/ml of N-CWS. PMID- 2267897 TI - [Ascitic fluid: the value of various biological tests in the differential diagnosis between cirrhotic and neoplastic ascites]. AB - The authors have analyzed sixty cases of ascites including twenty of neoplastic origin and thirty-six of cirrhotic origin in order to evaluate the usefulness of several laboratory tests for the differential diagnosis of ascites. The tests which gave more than 85% diagnostic accuracy were ascitic fluid concentrations of fibronectin and total protein, serum-ascites gradients of albumin and total protein concentrations, ascitic fluid concentrations of albumin and cholesterol. The last three tests gave a diagnostic accuracy of more than 92% at discriminant levels of 3.8 gr/dl, 1.6 gr/dl and 60 mg/dl, respectively. For these six tests, neoplastic ascites due to liver metastasis had values intermediate between cirrhotic ascites and neoplastic ascites due to peritoneal carcinomatosis. A serum-ascites albumin gradient of more than 1.1 gr/dl was indicative of portal hypertension in cirrhotic patients; the total protein serum-ascites gradient had a better diagnostic accuracy. Flow cytometry had less diagnostic accuracy than cytology; moreover, all cases with abnormal flow cytometry were already recognized by cytology. PMID- 2267898 TI - [Peutz-Jeghers syndrome. Description of a case and literature review]. AB - The authors describe the case of a 7 year old boy who presented an intestinal intussusception due to a large jejunal hamartomatous jejunal polyp. The preoperative diagnosis of Peutz-Jeghers syndrome was based on typical mucocutaneous pigmentation and confirmed by radiological examination including computerized tomography of the abdomen. Following recent data from the literature, a long-term surveillance is justified after diagnosis of this syndrome, since malignant degeneration may occur within the intestinal polyps as well as in other organs. PMID- 2267899 TI - Differential diagnosis and prognosis of cirrhosis: role of liver biopsy. AB - Histopathological examination of needle biopsies of the liver is a cornerstone in the diagnostic work-up on a patient with symptoms of chronic liver disease. It allows to confirm whether cirrhosis is present or not. In a considerable number of cases, this confirmation is definitive. In some cases, only a diagnostic level of suspicion is reached. In these cases, close collaboration between clinician and pathologist may increase the degree of diagnostic certainty. A reliable diagnosis of cirrhosis on liver biopsies requires careful consideration of differential diagnostic alternatives. Application of the full battery of histopathological techniques, including special stains, polarizing light and immunohistochemistry, allows to specify (or to help to specify) the aetiology in a substantial number of cases. The histopathologist should further look for information which bears on prognosis, and evaluate the stage, the activity and eventual complications by search of the corresponding histological changes. PMID- 2267900 TI - Hypoxemia in patients with liver cirrhosis. AB - Chronic liver disease is often accompanied by alterations in the pulmonary and cardiovascular systems as demonstrated by hypoxemia, hyperkinetic circulation and impaired pulmonary and systemic vascular resistance. In some patients these abnormalities are due to ventilation-perfusion imbalance and/or intrapulmonary shunting. Although the pathogenesis of these disturbances is unknown it can be hypothesized that vasodilating substances might bypass the liver and give rise to such changes in intrapulmonary vessels. The normalization of pulmonary perfusion after liver transplantation suggests a direct functional relationship between the liver and the lungs--a "hepatopulmonary syndrome"--similar to the functional renal failure widely known as the hepatorenal syndrome. PMID- 2267901 TI - [Extracellular matrix, hepatic fibrosis and anti-fibrosis treatment]. AB - Over recent years, the study of the extracellular matrix (ECM) in the liver has considerably progressed. The application of new biochemical and genetic techniques led to the discovery of 13 different collagen proteins and a growing number of collagen-associated proteins such as fibronectin, laminin and proteoglycans. Many of these proteins have been cloned and sequenced. Progress also includes a better knowledge of the biological roles of ECM components as well as its dynamic remodeling in various pathophysiological conditions. Even if the clinical goal of prophylaxis and therapy of fibrosis remains distant, progress can be anticipated in the near future as basic processes are being elucidated. PMID- 2267902 TI - [Medical treatment of primary biliary cirrhosis]. AB - The medical treatment of primary biliary cirrhosis can be divided into two parts: the treatment of the complications (cholestasis and portal hypertension) and the treatment of the underlying disease. As regards the treatment of the disease itself, there is to date no drug which has been shown to ameliorate the pathological process and to prolong survival: cyclosporine and ursodeoxycholic acid, recently used have shown promising responses in liver biochemistry but long term controlled studies are required to assess their effectiveness on the disease process and on survival. PMID- 2267903 TI - [Arterialization of the portal vein associated with a portocaval shunt: long-term results of a controlled prospective study]. AB - In order to evaluate the benefit of arterialization of the portal vein in conjunction with a therapeutic end-to-side porto-caval shunt, we started in December 1979 a prospective randomized study, comparing these two techniques in Child class A and B cirrhotic patients with a hepatopetal portal flow of at least 100 ml per min. Sixty-four patients have been included in the study: 33 underwent a porto-caval shunt (NART) and 31 were arterialized (ART). The two groups of patients were similar as regards clinical and hemodynamic parameters. The operative mortality was lower after arterialization, considering the whole group (ART: 6.5%, NART: 12%) and high risk patients (Child class B: ART: 0%, NART: 22%- emergency operation: ART: 0%, NART: 17%) but the differences were not statistically significant. Postoperative ascites was more frequent in arterialized patients (ART: 45%, NART: 18%; p = 0.02), with an increased need for reoperation (ART: 26%, NART: 6%; p less than 0.05). The mean follow-up period is 56.9 +/- 28.1 months (SD) for the 58 surviving patients. The five-year actuarial survival rate is 68% for ART patients and 60.6% for NART patients (NS). In child B patients the five-year actuarial survival rate is 75% in ART patients and 22% in NART patients (p less than 0.05). Actuarial estimation of arterialization patency--proved by angioscan--is 38% at five years. There were no significant differences in the incidences of postoperative and long-term encephalopathy and liver function between the two groups. In conclusion, arterialization of the portal vein in conjunction with a therapeutic end-to-side porto-caval shunt improved survival in high risk patients (Child class B), did not increase operative mortality in Child A and B patients, was followed by a higher incidence of postoperative ascites and did not decrease the incidence of long-term encephalopathy. PMID- 2267904 TI - Diuretic-resistant ascites in cirrhosis. Mechanism and treatment. AB - Refractory ascites (or diuretic-resistant ascites), i.e. ascites that cannot be mobilized by medical treatment (low sodium diet and high doses of furosemide and spironolactone) is an infrequent phenomenon in cirrhosis. It usually occurs in patients with functional renal failure as a consequence of alteration in both pharmacokinetics and pharmacodynamics of diuretics. Peritoneovenous shunting, a procedure which improves systemic hemodynamics and renal function and suppresses the plasma levels of renin, aldosterone, norepinephrine and antidiuretic hormone in cirrhotics with ascites, has been proposed as the treatment of choice in patients with refractory ascites. Unfortunately it is associated to a high rate of severe complications and does not prolong the survival of these patients. Moreover, in approximately one third of the patients the shunt becomes occluded within the first year after operation. Recent studies have shown that repeated large volume paracentesis (4-64 per day until disappearance of ascites) or total paracentesis (complete mobilization of ascites in only one paracentesis session) associated to i.v. albumin infusion are an effective and safe therapy of ascites. At present, there is only one controlled trial comparing therapeutic paracentesis versus peritoneo-venous shunt in the management of patients with refractory ascites. In this study, there were no significant difference between both therapeutic groups with respect to survival. However, the incidence of readmission to hospital for the treatment of ascites was higher in the paracentesis group. Therefore, both procedures are valid therapeutic alternatives for that type of patients. Future studies are necessary to investigate if there are subsets of cirrhotics with refractory ascites in which one of these two types of treatment is especially indicated. PMID- 2267905 TI - [Use of diuretics in the treatment of ascites in patients with cirrhosis]. AB - The cirrhotic patient with ascites has an increased tubular reabsorption of sodium. Diuretic therapy allows an urinary loss of sodium. The strongest diuretics which inhibit sodium reabsorption in the ascending limb of the loop of Henle (like furosemide) are not the most effective in cirrhotic patients; indeed the increased load of sodium arriving in the distal part of the tubule is reabsorbed because of hyperaldosteronism. Potassium-sparing diuretics, like spironolactone, which act beyond the sites of reabsorption of most of the filtered sodium, are mostly effective when combined with other diuretics which impair sodium reabsorption more proximally. We propose to treat ascites by: 1. Sodium restriction (maximum: 60 mmol per day); 2. Spironolactone 100 to 500 mg per day, combined with furosemide 40 to 200 mg per day if spironolactone does not induce a natriuretic effect. PMID- 2267906 TI - [Selection of patients with parenchymal cirrhosis for hepatic transplantation]. AB - The aim of our study was to design simple and practical quantitative scores or indices suitable for deciding a pre-liver transplantation work-up in patients with parenchymal cirrhosis. A Pugh score (combining five variables) superior to 8 or a p value inferior to 0.7 of a logistic regression equation containing only two variables (score of ascites and result of 14C aminopyrine breath test) were found to be highly effective for making this decision. PMID- 2267907 TI - [Hepatic transplantation in cirrhosis]. AB - The authors review the indications and outcome of liver transplantation for hepatic cirrhosis of various aetiologies in adults, on the basis of their experience and that of the literature. Up to 1989, they performed 107 liver transplantations in 93 adults, including 70 patients with cirrhosis: primary biliary cirrhosis (PBC) in 20, primary sclerosing cholangitis (PSC) in 2, secondary biliary cirrhosis in 1, post-necrotic cirrhosis in 35, alcoholic cirrhosis in 5, metabolic cirrhosis in 7. The best indications are PBC with rising bilirubinemia (greater than 5 mg/dl) or portal hypertension and PSC with severe and diffuse lesions. The outcome of transplantation was satisfactory in patients with PBC: 16 survived with a mean follow-up of 23 months. In patients transplanted for postnecrotic cirrhosis the outcome might be better if HBS is associated preoperatively with delta antigen: 6 patients of this group survived with a mean follow-up of 12.6 months while in the group of 8 patients with HBS not associated preoperatively with delta antigen, 6 patients survived with a mean follow-up of 12.8 months. There was a trend toward a higher hospital mortality after transplantation in cirrhotic patients with pulmonary arterio-venous shunts in comparison with cirrhotic patients without significant pulmonary arterio venous shunts preoperatively. PMID- 2267908 TI - 1991: 75th anniversary AARN. Our history--a proud heritage. The 1950's. PMID- 2267909 TI - Male nursing students' satisfaction with nursing education in Alberta. PMID- 2267911 TI - The environment. PMID- 2267910 TI - The Alberta Nursing Education Administrators: a beginning history. PMID- 2267912 TI - A tree to remember. PMID- 2267913 TI - From the pattern of human vocal muscle fibre innervation to functional remarks. AB - About 50% of the human vocal muscle fibres possess several endplates. The direct relation between the number of endplates and rate of contraction, which has been postulated in animals, does not apply to the human vocal muscle. However, it may be that this relation is not indispensable to the particular function this muscle is required to perform and undoubtedly justifies a possible pattern of selective muscle contraction, or better still, of a contraction regulated by a particular, independent mechanism. This mechanism is postulated and discussed. PMID- 2267914 TI - Scanning electron microscopy and immunoglobulins of the endolymphatic sac in normal human subjects and sensorineural deafness. With special reference to Meniere's disease. AB - The pathophysiology of the endolymphatic sac (ES) in Meniere's disease was studied by scanning electron microscopy and staining of immunoglobulins in the intradural portion of the ES. The peroxidase-antiperoxidase method by means of paraffin sections was used for staining of immunoglobulins. First, subjects without hearing impairment and malformation of the temporal bone, ranging from a 7-month-old fetus to an 80-year-old adult, were investigated. All subjects, including fetuses, showed well-arranged epithelial cells by scanning electron microscopy. The epithelial cells in the proximal portion of the intradural ES were oval, showing a tendency of transitional change to be flat as they drew near the distal portion of the ES. The epithelial cells consisted mostly of light cells, but sporadic dark cells were seen. Regarding the immunoglobulins. IgG was slightly positive in the epithelial and subepithelial layers. All 15 patients with Meniere's disease showed various types of degeneration of the epithelial cells though to varying degrees. However, these findings were also seen in cases of cochlear deafness. On the other hand, the ES of acoustic tumors, with retrocochlear or neural deafness revealed a normal finding, as found in healthy subjects. Inner ear deafness experimentally produced in animals by Kanamycin sulfate (KM) injection showed degeneration of the epithelial cells of the ES similar to that found in human cochlear deafness. IgG of the ES in Meniere's disease showed moderately evident deposits compared to normal subjects. However, this was also found not only in inner ear deafness other than Meniere's disease, but also in animal deafness experimentally produced by KM injection. It is very interesting to note that moderate endolymphatic hydrops was found in animals one year after Preyer's reflex had disappeared. It is postulated that endolymphatic hydrops develop because of impairment of endolymphatic fluid resorption at the rugose portion and stenosis of the lumen in the same portion, due to degeneration of the epithelial cells. From the above results, it is argued that degenerated epithelial cells and immunoglobulins of the ES in Meniere's disease may arise from the sequelae of cochlear deafness. It is also hypothesized that endolymphatic hydrops--at least in the terminal stage of Meniere's disease--may be consistent with the same pathophysiological conditions as in animal experiments. PMID- 2267915 TI - The tonsillar immune system: its response to exogenous antigens. AB - The palatine tonsil is the only lymphoid organ directly exposed to the outside environment. This characteristic anatomical feature appears to be immunologically significant with the defence activity primarily directed against exogenous antigens. However, the palatine tonsil is also often the site of secondary diseases, such as focal infections. This study investigated how the tonsil responds to horseradish peroxidase (HRP) dropped into the crypts and the effects of this response on the regional lymph node and the kidney as a distant organ. HRP entered through the microcrypts was phagocytosed by macrophages, gathered mostly around the vessels and emigrated to the regional lymph nodes. Anti-HRP antibody-producing cells were observed not only in the tonsil but also in the regional lymph node. In this long-term study with repeated immunization, fusion of the epithelial foot process and reduction of the anionic charge in the glomerulus were often found electron microscopically. This investigation suggests that the tonsil has important roles in the defence activity in relation to the general immune system; otherwise it becomes a primary site for focal infections. PMID- 2267916 TI - Socio-economic variables and pregnancy outcome. 2. Infant and child survival. AB - The effects of various social indicators on infant and child mortality were studied in Sweden with the use of a medical birth register to which census information was linked. Two years were studied: 1976 births linked to the 1975 census, and 1981 births linked to the 1980 census. Survival was followed to the age of 5 by linkage of the birth register with the death certificate register. The only statistically significant effect of a single socio-economic variable was that of housing conditions on perinatal death rate and postperinatal death rate up to the age of one. The family situation (e.g., cohabitation or not) had some effect, although it was not statistically significant. On the basis of cohabitation status and other social indicators, including housing conditions, we selected two groups: one privileged and the other underprivileged. Using crude mortality rates, we found no definite difference. There was evidence that the mortality rate had decreased more between 1976 and 1981 in the privileged than in the underprivileged group, but the difference may have been coincidental. After standardization for maternal age and parity, however, a difference appeared with a ratio of 1.14 between the underprivileged and the privileged groups, which was valid for deaths up to the age of one. After that age, no difference was seen. Following standardization for birthweight, the opposite was found: a higher weight-specific mortality rate in the privileged group than in the underprivileged group. The interpretation of these findings is discussed. PMID- 2267917 TI - The relationship between rooming-in/not rooming-in and breast-feeding variables. AB - We studied the relationship between rooming-in/not rooming-in and breast-feeding variables such as breast feeding frequency, breast milk intake, supplements of other human milk or 5% glucose solution, cumulative weight loss, weight recovery and hyperbilirubinemia. We found that the breast feeding frequency was significantly higher in infants rooming-in than in those not rooming-in. Intake of breast milk on days 3 and 5 was significantly lower and maximum weight loss was significantly higher in infants rooming-in than in those not rooming-in. Infants rooming-in also had less supplement of other human milk compared with non rooming-in infants (p less than 0.01). However, the weight increase per day from minimum to weight on day seven was higher in infants rooming-in than in non rooming-in infants (39.3 +/- 21.4 g/day vs. 31.4 +/- 15.3 g/day, p less than 0.01). The frequent suckling by rooming-in infants may explain, in part, the better weight gain, since frequent suckling may decrease energy consumption by reducing movement and crying during the early days of life, thus contributing to better weight gain. Our study suggests that some of the neonatal feeding problems related to breast feeding could be eliminated by education of mothers and nurses and by changes in hospital policies and practices in breast feeding. PMID- 2267918 TI - Incidence and etiology of neonatal septicaemia and meningitis in western Sweden 1975-1986. AB - In a retrospective study of neonatal septicaemia and meningitis in a defined region of western Sweden 1975-1986, 231 cases were identified. The incidence was 2.8/1000 live births. The case-fatality rate was 15%. thirty-three patients had meningitis. Only 55 patients (24%) had no known risk factors. Preterm delivery was a most important risk factor for both morbidity and mortality. The most common causative organisms were group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods, together isolated from 82% of the patients. The cases were approximately equally divided between very early, early and late onset infections. Group B streptococci were over-represented in very early onset infections in all birthweight groups and aerobic Gram-negative rods were the most common isolates from low birthweight infants with late onset infections. However, group B streptococci, Staphylococcus aureus and Gram-negative rods were found in all birthweight and gestational age groups. Thus, initial antimicrobial therapy must be equally broad in all neonates with suspected septicaemia. PMID- 2267919 TI - Decreased adherence, chemotaxis and phagocytic activities of neutrophils from preterm neonates. AB - Using microanalytic assays various phagocytic functions of separated neutrophils from preterm neonates (mean birthweight 1,506 g, n = 13) were simultaneously studied. Adherence of neutrophils to nylon fibre was decreased in cells from preterm infants (77.1 +/- 3.1%) when compared with adult controls (86.9 +/- 2.1%, mean +/- 1 SD, p less than 0.05). In addition neutrophil chemotaxis in response to zymosan activated serum was reduced in preterm neonates (131.9 +/- 19.7, adults 166.6 +/- 11.1, p less than 0.001); directed migration towards Formyl Methionyl-Leucyl-Phenylalanine was also decreased (preterm neonates 93.4 +/- 15, adults 111.1 +/- 16.8, p less than 0.05). Preterm infants had a higher percentage of slow moving neutrophils when compared with adults (p less than 0.001). Phagocytosis of Candida albicans was reduced in neutrophils from preterm neonates (phagocytic index: preterm neonates 41.4 +/- 12.7, adults 83 +/- 7.2). Adult neutrophils ingested more Candida per cell (p less than 0.001). Chemiluminescence, exocytosis of elastase and lactoferrin during uptake of opsonized zymosan was also reduced in neutrophils from preterm neonates. However, random migration, phagocytosis of Staphylococcus aureus and production of O2- in response to Phorbol myristate acetate or opsonized zymosan were identical in cells from either source. We conclude, that these abnormalities of neutrophils could predispose the preterm infant to serious and often overwhelming bacterial and fungal infections. PMID- 2267920 TI - Anti-infective factors in preterm human colostrum. AB - Feeding of the infection prone preterm neonate with concentrated immunologically active ingredients in the form of colostrum may have even more significant clinical implications than in the full term infants. The scarcity of knowledge on anti-infective factors in colostrum of mothers delivering prematurely prompted us to carry out this study. Colostrum was collected and analysed from 25 mothers delivering prematurely (Study group) and 10 delivering at term (Control group). Major anti-infective factors namely IgA, IgG, IgM, lactoferrin and lysozyme were quantitated and total cell, macrophage, lymphocyte and neutrophil counts were performed. The mean concentrations of IgA, lysozyme and lactoferrin of preterm colostrum were significantly higher than in full term colostrum (p less than 0.001). IgG and IgM were found to be similar in both groups. The absolute counts of total cells, macrophages, lymphocytes and neutrophils were found to be significantly higher in the preterm colostrum as compared to the full term colostrum (p less than 0.001). Though in both the groups IgA was the predominant immunoglobulin, the mean percentage of IgA in the study group was significantly higher as compared to the control group. Degree of prematurity did not have any influence on the anti-infective protein levels in colostrum. However total cells and macrophages were significantly higher in colostrum of mothers delivering severely preterm babies. PMID- 2267921 TI - Postenteritis enteropathy in infancy. A prospective study of 10 patients with special reference to growth pattern, long-term outcome and incidence. AB - Ten patients, who developed postenteritis enteropathy with chronic diarrhoea, failure to thrive and small intestinal mucosal damage after an episode of acute gastroenteritis, were studied prospectively. All patients experienced severe growth retardation. Maximum deviation of height and weight from mean values of age-correlated normal children were -1.7 and -3.1 SD (median values), respectively, as compared to -0.1 and 0 SD before onset of the illness. One child died after 14 months of illness. The long-term outcome was satisfactory for the 9 surviving children. For these children, treatment with an elemental diet (in some cases supplemented initially with parenteral nutrition) and later a lactose-free diet lead to resolution of diarrhoea within periods ranging from 0.5 to 10 months. The phase of catch-up growth lasted from 4 to 36 months, resulting in final height and weight deviating -0.6 and -0.8 SD (median values), respectively, from normal mean values. Attempt to predict duration of diarrhoea or length of catch-up growth phase by means of age, weight before illness, characteristics of small intestinal biopsy or maximum deviation of height or weight were unsuccessful. The incidence of postenteritis enteropathy for children of North European ethnic origin was estimated to be 7.6/1,000,000 children below 7 years of age/year, corresponding to 1.2/1,000 children hospitalized for acute gastroenteritis. PMID- 2267922 TI - Placebo controlled trial of systemic corticosteroids in acute childhood asthma. AB - In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma. PMID- 2267923 TI - Growth hormone secretion in Prader-Willi syndrome. AB - Integrated 12-hour growth hormone secretion studies, peak growth hormone response to clonidine provocation. Somatomedin-C levels, T-4 and TSH levels were studied in six growth-retarded children with the Prader-Willi syndrome, of whom five had a 15 q-karyotype. Only one of the subjects was obese. All showed abnormally low growth hormone secretion. None achieved a nocturnal peak above 10 micrograms/l, none had a mean nocturnal level over 1.8, and none showed a level above 8 micrograms/l after clonidine provocation. These findings contrasted with normal TSH in all and normal T-4 in five. These findings suggest that the poor linear growth in the Prader-Willi syndrome is caused by a true deficiency of growth hormone secretion, and that the low growth hormone levels observed in such cases are not an artifact of obesity. PMID- 2267924 TI - Hereditary tyrosinemia of chronic course without rickets and renal tubular dysfunction. AB - Three patients with hereditary tyrosinemia type 1, two brothers and one girl, studied at the age of 5, 12 and 15 years, respectively, had neither generalized hyperaminoaciduria, glucosuria nor clinical symptoms of rickets. Untreated the elder brother had only slightly elevated plasma tyrosine level (141 mumol/l, normal less than 80), and low excretion of p-hydroxyphenyllactate. He presented with pronounced thrombocytopenia (3 X 10(9)/l). At 13 years of age he contracted hepatocellular carcinoma. The younger brother presented with serum tyrosine of 318 mumol/l and thrombocyte count 48 X 10(9)/l. Succinylacetone in urine was elevated in both, 30 and 79 mumol/mmol creatinine, respectively. The female patient was investigated for hepatomegaly in infancy, atypical tyrosinemia being considered, but afterwards developed normally without diet or any other treatment until she contracted hepatoma at the age of 15 years. Her plasma tyrosine level was 600-700 mumol/l, and she excreted large amounts of p-hydroxyphenyllactate. Succinylacetone in urine was low but elevated (8 mumol/mmol creatinine). The fumarylacetoacetase activity in fibroblasts from the brothers and in lymphocytes from the girl was less than 5% and 10% of control levels, respectively. In conclusion, the chronic form of hereditary tyrosinemia may occur without evidence of renal tubular dysfunction. PMID- 2267925 TI - Physical and laboratory characteristics of heterozygote carriers of the Fanconi aplasia gene. AB - Fanconi anaemia (FA) is a recessively inherited disorder associated with a typical physical appearance and a spectrum of clinical and laboratory characteristics. Parental heterozygotes of FA patients are superficially normal in appearance and lack overt laboratory abnormalities. Furthermore, they are indistinguishable from normal subjects on chromosome analysis. In order to determine if any of the clinical or laboratory abnormalities seen in FA patients were detectable to a lesser degree in heterozygotes, we carried out detailed skeletal measurement and laboratory investigation on 16 obligate FA heterozygotes and compared the results with 40 normal control subjects. Skeletal proportions in FA heterozygotes showed significant differences from normal subjects in the ratio of the height to the inter-acromial distance (p less than 0.001), and in having significantly shorter forearms (p less than 0.05). Apart from two patients with presumed iron deficiency, haemoglobin levels were normal, but three patients showed neutropenia (less than 1.5 X 10(9)/l). Foetal haemoglobin measurements were significantly higher (p less than 0.01) and natural killer cell subsets lower (p less than 0.05) in heterozygotes. Significantly reduced mitogenetic responses to phytohaemagglutinin and interleukin-2 of peripheral blood lymphocytes in heterozygotes was also demonstrated. These results suggest that heterozygotes show minor physical and haematological abnormalities consistent with partial expression of the Fanconi gene in the heterozygote. PMID- 2267926 TI - Haemolytic crises due to glucose-6-phosphate dehydrogenase deficiency in the mid southern region of Turkey. AB - Clinical and laboratory evaluation of 60 boys with hemizygous, 12 girls with homozygous, and 11 girls with heterozygous erythrocyte glucose-6-phosphate dehydrogenase deficiency was made during haemolytic crisis. The main clinical symptoms were paleness, dark urine and oliguria. Only one patient needed peritoneal dialysis. Coexistence of glucose-6-phosphate dehydrogenase deficiency associated with haemoglobinopathy was found to be higher than expected (32 out of 83 cases). Also, the high prevalence of glucose-6-phosphate dehydrogenase deficiency among females with homozygous and heterozygous disease was surprising. The precipitating factors of haemolysis were variable. Rather than antimalarial and antipyretic-analgesic drugs, infections seemed to be the main haemolytic factor. PMID- 2267927 TI - Infantile hydrocephalus--the impact of enhanced preterm survival. AB - The epidemiology of infantile hydrocephalus (IH) in the birth years 1983-86 was investigated in the south-western health care region of Sweden. The study was made as a continuation of a previous one which had shown a significant increase in the prevalence of IH in 1967-82. That rise was entirely referable to the relatively larger number of preterm IH infants born in 1979-82 and was considered to be due to the enhanced survival, especially of very preterm infants. The present series comprised 57 liveborn IH infants--27 preterms and 30 born at term. The livebirth prevalence of IH was 0.64 per 1,000, 0.30 for preterm and 0.34 for fullterm infants. The high prevalence of preterm IH infants in 1979-82 had persisted, but had not increased further. This might indicate an improved outcome in preterm survivors in the period 1983-86, as the survival rate had continued to increase. The striking predominance of a perinatal aetiology of IH in very preterm infants could be confirmed: 90% had had intraventricular haemorrhages verified by ultrasound in the postpartum period. The outcome in very preterm surviving infants with IH was still alarmingly poor: 78% had cerebral palsy, 72% mental deficiency, and 56% epilepsy. PMID- 2267928 TI - Gamma-aminobutyric acid concentration in lumbar cerebrospinal fluid from patients with febrile convulsions and controls. AB - The cerebrospinal fluid (CSF) concentration of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was analysed in 41 children with febrile convulsions (FC), 41 febrile controls of similar age (control group 1), and 59 controls, who had no fever and/or were outside the age range for FC (control group 2). A significant correlation between CSF-GABA and age was demonstrated for controls (1 + 2) (r = 0.63, p less than 0.00001), as well as for patients with FC (r = 0.42, p = 0.003). Patients with FC did not differ significantly from control group 1 in respect to CSF-GABA. Duration of FC was related to both CSF-GABA and age (GABA: r = -0.29, p less than 0.05; age: r = -0.32, p less than 0.05). For 56 controls (1 + 2) greater than 1 year of age, a significant negative correlation between CFC-GABA and body temperature was found (r = -0.34, p = 0.01). The low CSF-GABA in the FC-labile age group, the negative correlation of CSF-GABA to body temperature, and the negative correlation of the duration of FC to both CSF-GABA and age, all indicate that GABA could be of importance in the pathophysiology of FC. PMID- 2267929 TI - Severe mental retardation in Jordanian children. A retrospective study. AB - The etiology of severe mental retardation has not previously been studied in Jordan. In a group of 203 mainly severely mentally retarded children born 1975 1985, we found the etiology to be related to two main factors: (1) sequele from high perinatal morbidity or meningitis in infancy leading to a combination of severe mental retardation and cerebral palsy; (2) a high degree of intermarriage and a high frequency of retarded siblings indicating that genetic causes of MR are common. The results underscore the importance of further development of antenatal and perinatal care, especially for poor people and the need of genetic counselling. PMID- 2267930 TI - Public awareness of and attitudes toward cerebral palsy in a nation-wide adult population. AB - Of 1,200 people randomly sampled from the total Finnish population, cerebral palsy was known to 95.4% and its meaning to 60.7%. Nine of ten (88.4%) would let their children play with a child suffering from cerebral palsy. A total of 48% stated that they would, other circumstances being equal, hire persons with cerebral palsy. Half (47.5%) of the subjects regarded it as possible and a further 28.0% as fully possible for individuals with cerebral palsy to make and maintain a family of their own. A good knowledge of cerebral palsy was independently related to a good basic education, age of more than 24 years, female sex and Finnish as native language. A positive attitude toward people with cerebral palsy was independently related to Finnish as native language and a good basic education. A good knowledge of cerebral palsy fostered a positive attitude toward people with this disease. PMID- 2267931 TI - Noninvasive estimation of aortic valve areas in children with aortic stenosis. AB - Fifteen children with aortic stenosis were examined with Echo-Doppler cardiography in order to evaluate the use of the continuity equation to calculate the aortic valve area. The results were compared to invasive estimates of valve area calculated with the Gorlin's equation. A close correlation between the two methods, r = 0.94, was found and it is concluded that even in children an accurate estimate of valve area can be expected with the use of the continuity equation. PMID- 2267932 TI - Urinary excretion of N-acetyl-beta-D-glucosaminidase in children with NH4Cl metabolic acidosis. PMID- 2267934 TI - Delayed-onset dyskinetic 'cerebral palsy--a late effect of perinatal asphyxia? AB - A 12-year-old girl, born full term after severe pre- and peripartal asphyxia, with transient abnormal newborn neurology and slight motor development deviations but no cerebral palsy syndrome, is described. At the age of 5, she developed a slowly progressive dyskinetic hemisyndrome, initially uncoordinated hyperkinetic movements in her left arm, dystonic posturing then supervened. Since the age of 11, her right side had also slowly become involved. As extensive examinations excluded other causes, it is concluded that this case represents a delayed onset dyskinetic 'CP-syndrome' subsequent to a postanoxic non-progressive insult to the basal ganglia, but with a well compensated functional integrity before the age of 5. PMID- 2267933 TI - Colchicine therapy in immune thrombocytopenic purpura. PMID- 2267935 TI - Cavernous haemangioma of the jejunum. Long-standing anaemia in a child. AB - A 15-year-old boy who had been examined for almost lifelong iron deficiency anaemia caused by occult gastrointestinal bleeding was eventually, by abdominal surgery, found to have a cavernous haemangioma of the jejunum. A diagnostic approach is described and the importance of systematic evaluation and subsequent diagnosis in such patients is stressed. PMID- 2267936 TI - Neurogenic pulmonary oedema. AB - Neurogenic pulmonary oedema followed a subarachnoid haemorrhage secondary to an arteriovenous malformation in an eight-year-old boy. Despite a complicated course, he made a full recovery. Neurogenic pulmonary oedema is rare in childhood. It is sudden in onset, and potentially fatal, but is amenable to prompt and vigorous treatment. PMID- 2267937 TI - Health monitoring of laboratory animals at the national veterinary institute (SVA). PMID- 2267938 TI - Laboratory animal health monitoring: an introductory survey of university mouse breeding colonies in Stockholm. PMID- 2267939 TI - A survey on the reduction of animal use in projects funded by the National Board for Laboratory Animals (CFN) 1979-1987. AB - A survey was carried out on the reduction of animal use in the projects funded by the CFN between 1979 and 1987. 63 projects had received funds. 37 projects were reported in time for the symposium, and the results were presented there; surveys on another 11 projects were received later. The projects funded covered different areas, basic research, testing, evaluation studies, biological production, vaccine testing, education, improved animal experimental techniques, therapy and problems with in vitro toxicology. They were all in line with the objective of the CFN, which is to reduce animal experimentation in Sweden. A definite reduction in animal use is reported in some studies and predicted to take place as a result of others, either relatively soon or in a longer perspective. The survey has a bias, since the scientists themselves were asked to report on their projects and evaluate the effects of the reduction in the use of animals. However, the answers give rise to new interesting questions about future possibilities of animal reduction in a variety of areas and this points at one of the main conclusions, namely the need for further investigation into areas of interest. In order to work out a realistic strategy for reduction of animal use, a coordinating body is needed to investigate areas of promise, where animals either can be reduced or experimental techniques refined, and develop strategies for addressing target areas. The CFN should play such an offensive role. PMID- 2267940 TI - Structural and functional properties of thyroid follicle cells in culture. PMID- 2267942 TI - Intercellular communication: a useful test for tumour promoters? PMID- 2267941 TI - Human neuroblastoma cells in culture: a model for neuronal cell differentiation and function. AB - The human neuroblastoma cell line, SH-SY5Y, differentiates into neuron-like cells according to morphological, biochemical and functional criteria when treated with biologically active phorbol-esters. The differentiated phenotype is described and alterations in proto-oncogene expression in connection with growth control and differentiation are presented and discussed. PMID- 2267943 TI - The metabolism of xenobiotics and its relationship to toxicity/genotoxicity: studies with human lymphocytes. AB - Most compounds considered to be foreign to the human body are rather hydrophobic and chemically inert. Because of their hydrophobicity, xenobiotics enter the body easily by diffusion through biological membranes, are difficult to excrete in unchanged form in the urine and bile and accumulate in hydrophobic compartments of the cell, including the phospholipid bilayer of membranes, where they can disturb normal cellular functions. In order to transform xenobiotics into products which are more readily excretable, enzymes of detoxication first activate these substances (primarily via the cytochrome P-450 monooxygenase system) to intermediates which are often highly electrophilic and reactive, such as epoxides, free radicals and carbonium ions. These intermediates are then partially inactivated and their solubility in water simultaneously increased through the addition of water (by epoxide hydrolases) or conjugation with glutathione (by glutathione transferases). Finally, an additional increase in water solubility can be achieved by conjugation with, for example, sulfate (via sulfotransferases) and/or glucuronic acid (via UDP-glucuronyltransferases). Unfortunately, reactive intermediates of xenobiotic metabolism which are not inactivated sufficiently rapidly can bind covalently to many nucleophilic groups in the cell, including those on DNA, RNA and protein. Most often, because of various cellular defense mechanisms, such binding causes no serious damage. However, in some cases toxic and/or genotoxic effects may be produced. As an alternative to experimentation with animals, we have examined xenobiotic metabolism in circulating mononuclear leukocytes from human beings. Certain enzymes of detoxication--including membrane-bound and cytosolic epoxide hydrolases and cytosolic glutathione transferases--can be easily measured and characterized in preparations from these cells. Autosomal dominant hereditary differences of at least several hundred-fold in the activity of glutathione transferase mu in circulating human lymphocytes were observed, differences which may be of value in predicting an individual's risk for toxic/genotoxic damage after exposure to certain xenobiotics. PMID- 2267944 TI - Midbrain micromass cultures: a model for studies of teratogenic and sub teratogenic effects on CNS development. PMID- 2267945 TI - Drug induced esophageal lesions studied in vitro. AB - This paper describes an in vitro method of studying the esophago-irritant potential of oral formulations of drugs. Porcine esophagus was used. The method offers the possibility of studying muscle activity and enzyme leakage (e.g. LDH) and of performing histomorphology of the exposed preparations. Examples of drugs which were tested are alprenolol (Aptin), propranolol (Inderal), doxycycline (Idocyklin) and (Vibramycin) and emepronium bromide (Cetiprin). Concerning effects on muscle activity, Aptic caused a marginal contraction while Cetiprin caused a relaxation of the esophagus preparation. Increased LDH-leakage was noted during exposure with the above mentioned pills in comparison with concurrent control preparations. Histopathological examination disclosed morphological changes such as softening and necrosis of the squamous epithelium of the esophageal mucosa after exposure to drugs like Idocyklin and Aptin. PMID- 2267946 TI - Molecular analysis of mutation at the human hprt locus. PMID- 2267947 TI - In vitro methods, past successes and future challenges. PMID- 2267948 TI - Carcinogenesis studies in human epithelial tissues and cells in vitro: emphasis on serum-free culture conditions and transformation studies. AB - Serum-free techniques are now available for maintenance of normal non-tumorous human tissues for periods ranging from days to months, and for the selective culture of normal replicative epithelial cells from common sites of human cancer. These model systems are particularly useful in mechanistic studies of molecular and cellular events related to multistep carcinogenesis, including studies of carcinogen metabolism, related DNA damage and repair, toxicity, growth and differentiation, and, moreover, transformation of the cells to immortal and malignant phenotypes. Studies with cultured human epithelial tissues and cells allow comparisons among individuals on both a tissue and cellular level, and link clinical and epidemiologic studies with laboratory animal studies in efforts to determine the influence of predisposing factors and environment in the development of human cancers. PMID- 2267949 TI - The effect of a meal on cardiac output in man at rest and during moderate exercise. AB - Cardiac output at rest increased by 11-63% in a group of healthy individuals after the consumption of a medium-sized, mixed meal. The maximum post-prandial levels of cardiac output were reached from 10 to 30 min after termination of the meal. Cardiac output values at rest fluctuate around a mean level, and this fluctuation was considerably more marked after a meal, when changes in cardiac output from one 15-s period to another could be of the order of 1-1.5 l min-1. Recording of flow in the superior mesenteric artery before and also after a meal was successful in two subjects in whom anatomical conditions were favourable. Flow in the artery was approximately doubled from the fasting to the post prandial situation, an augmentation that accounted for about 50% of the concomitant increase in cardiac output. The increases in cardiac output caused by 2-min bouts of standardized, moderate and rhythmic exercise were consistently larger in the post-prandial than in the fasting situation. It thus appears that any tendency for redistribution of blood flow, for example from the gastrointestinal tract to the working muscles, during moderately intense exercise is less marked after a meal than before. PMID- 2267950 TI - Haemodynamic information encoded in the aortic baroreceptor discharge during haemorrhage. AB - This study concerns the function of aortic baroreceptors during slow haemorrhage, in particular the mechanisms by which baroreceptors respond to hypovolaemia in the absence of hypotension and the manner in which haemodynamic information is encoded in the aortic nerve discharge. Beagle dogs, anaesthetized with morphine and chloralose, were instrumented for the recording of aortic pressure, aortic diameter, aortic flow and aortic nerve activity. The animals were subjected to slow haemorrhage (0.4 ml kg-1 min-1) of 20% of the estimated blood volume. Mean aortic pressure remained unchanged, whereas mean aortic diameter, mean aortic tension and aortic baroreceptor activity decreased during the haemorrhage. Baroreceptor sensitivity to mean aortic pressure, mean aortic diameter and mean aortic tension decreased as the haemorrhage proceeded. Also, the sensitivity of baroreceptors to mean aortic pressure and mean aortic diameter during acute pressure stimulation was attenuated. The results indicate that during non hypotensive haemorrhage aortic baroreceptor discharge is reduced by two mechanisms: firstly, via constriction and stiffening of aortic smooth muscle and, secondly, via direct effects of the compensatory mechanisms on the baroreceptors. The reduced sensitivity renders the baroreceptors capable of responding to hypovolaemia prior to the onset of hypotension. In the regression analysis, systolic aortic diameter proved to be the best determinant of baroreceptor activity (r = 0.877). Of the neural variables, impulses per cardiac cycle and average discharge rate were the most reliable, but no difference in the relative importance of these two parameters could be observed. PMID- 2267951 TI - Forces involved in transcapillary fluid movement in exercising cat skeletal muscle. AB - Average capillary pressure (Pc) close to the venous end (fluid equilibrium point) of the exchange vessels (denoted Pc,v), arterial (PA) and venous pressure, and the rate of net transcapillary fluid flux were continuously recorded in sympathectomized muscle during 30 min of graded exercise and for 30 min in the post-exercise period. Regional changes in colloid osmotic pressure (pi pl) and total osmolality in plasma, the latter reflecting work-induced interstitial hyperosmolality, were measured at intervals. In the control state at rest with a Starling fluid equilibrium, Pc,v averaged 17.6 +/- 0.8 mmHg. Exercise caused a rapid transcapillary plasma fluid loss, the net driving pressure for which in the initial phase of heavy work was 58 mmHg (transcapillary fluid flux divided by the capillary filtration coefficient). This comprised an increase in Pc,v of 16 mmHg, a nonprotein osmotic force (Posm) related to exercise-induced tissue hyperosmolality corresponding to 46 mmHg and an opposing force established by a raised pi pl of 4 mmHg. A theoretical analysis indicated that the main fraction of the osmotic fluid loss passed through transcellular ultrapores and only a minor part through conventional small pores. In spite of the fact that Pc remained high throughout the exercise period, the outward fluid flux gradually declined and a Starling equilibrium was re-established 23 min after the commencement of heavy exercise. This was explained by a gradual decline of Posm and apparently also by a secondary increase in tissue pressure (Pif) and/or a decrease in interstitial colloid osmotic pressure (pi if). Net fluid absorption occurred in the post-exercise period as a result of a gradual decrease in Pc, reversed transcapillary Posm and also maintained high Pif and/or low pi if. Exercise (even light) abolished normal Pc autoregulation, implying that the filtration component of net transcapillary fluid flux becomes distinctly modulated if PA is altered. PMID- 2267952 TI - Effects of sympathetic stimulation on C-fibre response after peripheral nerve compression: an experimental study in the rabbit common peroneal nerve. AB - Non-myelinated C-fibre responses during sympathetic trunk stimulation were studied in rabbit common peroneal nerve 2 weeks after the nerve had been subjected to compression at 400 mmHg for 30 min. Our previous studies have demonstrated that during sympathetic trunk stimulation the compound action potential of uninjured somatic C-fibres is characterized by a reduced amplitude and an increased latency. In the present study, nerve compression changed the C fibre response to sympathetic stimulation. Three out of eight nerves reacted to nerve compression by increased C-fibre compound action potential amplitude in response to sympathetic stimulation. In three other rabbits with compressed nerves the C-fibre action potential amplitude was unchanged, and in the remaining two rabbits the action potential amplitude was decreased during sympathetic stimulation. The action potential latency increased in all tested compressed C fibres. The phenomenon of increased C-fibre amplitude during sympathetic activation has not been observed in uninjured nerves. As in uninjured nerves, noradrenaline infusion produced an increased C-fibre action potential amplitude and latency in six animals. Sympathetic stimulation did not affect the A-fibre response. These results indicate that sympathetic activity influences the conduction properties in C-fibres of somatic origin and that the response can be changed after a nerve injury. The findings may be of importance for the understanding of pain aggravation in different types of nerve injuries during increased sympathetic activity. PMID- 2267953 TI - Adenosine A1-receptor-mediated inhibition of evoked acetylcholine release in the rat hippocampus does not depend on protein kinase C. AB - The possible involvement of protein kinase C and/or a lipoxygenase product in the mechanism by which adenosine inhibits release of [3H]acetylcholine evoked by electrical pulses from [3H]choline-labelled hippocampal slices was examined. For comparison, the muscarinic autoreceptors were examined using carbachol. The order of potency of adenosine analogues (CHA = R-PIA greater than NECA much greater than CGS 21680, CV 1808) indicates that the adenosine receptor responsible is of the A1 subtype. Adenosine (10 microM) and R-PIA (0.1 microM) were virtually equiactive as inhibitors and were antagonized to an equal extent by 8-CPT with a potency (IC50 approximately 25 nM) which is also compatible with A1-receptor mediation. The effects of carbachol and of R-PIA were not antagonized by the lipoxygenase inhibitor NDGA (10 or 50 microM). Stimulation of protein kinase C by the phorbol ester 4 beta-phorbol 12,13-dibutyrate caused a concentration dependent increase in stimulation-evoked 3H overflow, but did not antagonize the presynaptic inhibitory effect of R-PIA or carbachol (0.01-1 microM). Staurosporine (0.1 microM), which inhibited the stimulating effect of phorbol dibutyrate, did not alter the effects of carbachol or R-PIA. The presynaptic effects of phorbol dibutyrate, R-PIA and adenosine were reduced by pretreatment with N-ethylmaleimide (100 microM for 10 min), which inactivates G-proteins. The evoked transmitter release was unaffected by nifedipine (1 microM) in the presence and in the absence of phorbol dibutyrate. These results indicate that adenosine, by acting at presynaptic A1-receptors, reduces transmitter release by a mechanism that involves neither an NDGA-sensitive lipoxygenase nor protein kinase C. The results also indicate that the enhancement of transmitter release by phorbol esters is due to protein kinase C activation and that a G-protein may be involved in the effect but a dihydropyridine-sensitive L-type Ca2+ channel probably is not. PMID- 2267954 TI - Acute effect of ethanol on the pattern of behavioural specialization of neurons in the limbic cortex of the freely moving rabbit. AB - Single-unit activity was studied in the limbic cortex of eight freely moving rabbits in order to find out what kind of changes in the organization of unit activity correlate with behavioural disturbances following an acute administration of ethanol (1 g kg-1). The rabbits were taught to acquire food by pressing pedals in the experimental cage. Unit activity was recorded during this behaviour in a control experiment and the alcohol experiment took place the next day. The number of behavioural mistakes significantly increased in the alcohol experiments. The pattern of behavioural specialization of the units also differed between the control and alcohol experiments. In the control experiments 55% of units did not show any constant activations in relation to the behavioural phases (non-involved units), 28% of the units were constantly activated in relation to one or more behavioural phases learned in the cage (e.g. use of pedals; L units) and 17% of units showed activations in relation to the behaviour learned before the teaching of food acquisition (e.g. movements in general; M units). In the alcohol experiments the number of active units decreased by one-third compared with that found in the control experiments. The relative number of non-involved units did not change, whereas the relation between L and M units was reversed (11% L units and 34% M units). This was the result of a decrease in the number of active L units, mainly in the upper layers of the cortex. The results indicate that ethanol has a selective depressing effect on cortical neurons with different behavioural specialization, which could explain the behavioural disturbances observed in the alcohol experiments. PMID- 2267955 TI - Testosterone elevates pituitary prolactin content of long-term castrated rats under constant but not under periodic light. AB - Intact and castrated male rats were kept for 1 week under constant or periodic light, during which time they received daily injections of either vehicle or testosterone propionate (125 or 250 micrograms day-1). Immediately after the experiment the rats were decapitated and serum and pituitary prolactin were measured radioimmunologically. The pituitary prolactin content was decreased after castration in both lighting conditions. Daily testosterone injections elevated the pituitary prolactin content of the castrated rats to the level of the intact rats in constant-light conditions but were ineffective under periodic light. Serum prolactin concentrations were not affected by constant light. We have previously shown that testosterone decreases the serum luteinizing hormone concentration of castrated rats more effectively under constant than under periodic light. In the present study we showed that serum prolactin was not elevated in constant light and thus could not be the cause of increased testosterone sensitivity. We also showed that testosterone elevates the pituitary prolactin content of castrated rats under constant but not under periodic light. This finding gives further support to the hypothesis that constant light sensitizes the hypothalamo-pituitary axis of castrated male rats to the effects of testosterone. PMID- 2267956 TI - Feeding-induced oxytocin release in dairy cows. PMID- 2267958 TI - The return of Agamemnon. Or what quality control brings. PMID- 2267957 TI - In-vivo stimulatory effects of mammalian gonadotropin-releasing hormone in female frog, Rana esculenta, during the recovery phase. PMID- 2267959 TI - Impact of family physicians' cessation of obstetric care. PMID- 2267960 TI - Gametocytocidal activity of the antimalarial alpha/beta arteether against Plasmodium cynomolgi B. AB - A new sesquiterpene lactone alpha/beta arteether (a 30:70 mixture of enantiomers), which possesses very high blood schizontocidal activity, has been evaluated for gametocytocidal/sporontocidal action against Plasmodium cynomolgi B infection in the rhesus monkey. This paper reports gametocytocidal action of this new antimalarial drug at 2.5-5 mg/kg (single im dose) against P. cynomologi B as shown by the complete absence of mosquito infectivity. No sporontocidal action was demonstrable in the vector at a dose of up to 20-50 mg/kg im. PMID- 2267961 TI - Biochemical characterization of Plasmodium falciparum hemozoin. AB - Hemozoin, the pigment granule which develops within the blood stage food vacuole of the malaria parasite Plasmodium falciparum, was biochemically characterized. Hemozoin was found to be composed of 65% protein, 16% ferriprotoporphyrin-IX (hematin), 6% carbohydrate, and trace amounts of lipid and nucleic acids. The overwhelming majority of the protein component is a mixture of native and denatured human globin non-covalently associated with the metalloporphyrin. Immunoelectron microscopy, employing anti-human hemoglobin as a probe, identified in situ association of hemoglobin with hemozoin. Hemozoin produced within diabetic blood had a higher proportion of carbohydrate, suggesting that the carbohydrate component comes from non-enzymatic glycosylation of hemoglobin. PMID- 2267962 TI - Immunodot assay of Plasmodium falciparum sporozoites in mosquitoes using a direct binding membrane system. AB - We describe a membrane based immunodot assay for the detection of Plasmodium falciparum sporozoites mixed with mosquitoes. A crude sodium dodecyl sulfate extract of mosquitoes and sporozoites is passed through a bi-layered membrane system, the top layer being a polyvinyldiene difluoride hydrophilic pre-filter which screens out debris but allows the passage of antigen. Sporozoite, as well as mosquito, proteins are bound to the hydrophobic membrane below. This membrane was probed with a monoclonal antibody to the repeat region of the P. falciparum circumsporozoite protein, a peroxidase labeled second antibody and a tetramethyl benzidine substrate. The method detects as few as 10 sporozoites/mosquito or 100 sporozoites in a pool of 10. PMID- 2267963 TI - Automated flow cytometric analysis of drug susceptibility of malaria parasites. AB - A method is described for the fully automated reading of Plasmodium falciparum drug susceptibility tests. Cultured material was fixed and could be stored for greater than or equal to 6 months until analysis. The parasites were stained for DNA with the fluorescent dye Hoechst 33258 and analyzed by flow cytometry. The procedure was done in 96-well microtiter plates, after which the material was directed through the sensing region in the flow cytometer. The data resulting from the analysis were stored by microcomputer and processed by a program developed for this purpose. Using this method, a number of different parameters describing the growth in culture can be assessed. PMID- 2267964 TI - A comparative study of gastrointestinal infections in United States soldiers receiving doxycycline or mefloquine for malaria prophylaxis. AB - A double blind study of daily doxycycline (100 mg) vs. weekly mefloquine (250 mg) was performed on United States soldiers training in Thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections. During a 5 week period, 49% (58/119) of soldiers receiving doxycycline and 48% (64/134) of soldiers receiving mefloquine reported an episode of diarrhea. Infection with bacterial enteric pathogens was identified in 39% (47/119) of soldiers taking doxycycline and 46% (62/134) of soldiers taking mefloquine. Forty-four percent (59/134) of soldiers receiving mefloquine and 36% (43/119) of soldiers receiving doxycycline were infected with enterotoxigenic Escherichia coli (ETEC), while 9% (12/134) of soldiers receiving mefloquine and 4% of soldiers receiving doxycycline were infected with Campylobacter. Side effects from either medication were minimal. After 5 weeks in Thailand, the percent of non-ETEC strains resistant to greater than or equal to 2 antibiotics increased from 65% (77/119) to 86% (95/111) in soldiers on mefloquine and from 79% (84/106) to 93% (88/95) in soldiers on doxycycline. Doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to Thailand where ETEC and other bacterial pathogens are often resistant to tetracyclines. PMID- 2267965 TI - Mucocutaneous leishmaniasis due to Leishmania (Leishmania) infantum: biochemical characterization. AB - A vegetative mass in the right nasal cavity of a 62-year-old man from Palma de Mallorca, Spain, was found to be due to Leishmania. The organism was isolated in culture and characterized by in situ hybridization, Southern blot hybridization, and isoenzyme analysis; it was thus demonstrated to be the most common enzyme variant 1 (MON 1) of Leishmania (Leishmania) infantum. PMID- 2267966 TI - Leishmania mexicana complex: human infections in the Republic of Panama. AB - Parasites of the genus Leishmania responsible for human cutaneous leishmaniasis in the New World form 2 major taxonomic divisions: the Leishmania braziliensis and the L. mexicana complexes. We report the isolation and characterization of the L. mexicana complex among humans in the Republic of Panama. Characterization was based on parasite morphology, pathogenesis in infected golden hamsters, cellulose acetate isoenzyme electrophoretic mobilities, and membrane-specific monoclonal antibodies using the radioimmune binding assay technique. PMID- 2267967 TI - Infectivity of the subspecies of the Leishmania braziliensis complex in vivo and in vitro. AB - The infectivity of Leishmania braziliensis ssp. in relation to their growth kinetics in Senekjie's medium was determined using the human macrophage cell line U937 and inbred hamsters. In both systems, infectivity was shown to be distinctive for each subspecies. While L. b. panamensis promastigotes from 6-day old cultures (early stationary phase) were more infective than parasites from any other culture day, L. b. guyanensis and L. b. braziliensis reached maximum infectivity on days 8-10 and day 10 (late stationary phase of growth), respectively. Although maximum infectivity occurred during stationary growth, strict growth phase dependency was not observed. The populations of parasites on these culture days were composed mostly of small, highly motile promastigotes with flagella 2-3 times the length of their cell bodies. These promastigotes resembled the infective forms transmitted by the sand fly vector. A distinct pathological picture characterized the disease caused by the different WHO reference strains for these subspecies in hamsters: L. b. guyanensis developed the most severe lesions, while moderate and inconspicuous lesions were observed when L. b. panamensis and L. b. braziliensis, respectively, constituted the inocula. PMID- 2267969 TI - Wasting and macrophage production of tumor necrosis factor/cachectin and interleukin 1 in experimental visceral leishmaniasis. AB - Wasting and secretion of the catabolic cytokines tumor necrosis factor (TNF)/cachectin and interleukin 1 (IL-1) were assessed in weanling Syrian hamsters infected with Leishmania donovani amastigotes. Whereas the mean weight of uninfected animals increased progressively over 9 weeks, the mean weight of infected animals plateaued at 4-6 weeks and then decreased progressively until death. Splenic mononuclear cells from control hamsters produced 11.3 +/- 8.3 (SD) ng TNF/10(6) mononuclear cells/24 hr. TNF secretion in infected animals was greater than the mean +/- 2 SD of controls in 1 of 3 hamsters at 2 weeks post infection and in 8 of 9 hamsters at weeks 4-8. The mean TNF secreted by infected animals studied at weeks 4-8 was 371 (range 28-800) ng TNF/10(6) mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 +/- 2.7 pg IL-1/10(6) mononuclear cells/24 hr. At 2 weeks, mononuclear cells from 2 of 3 infected animals secreted amounts of IL-1 greater than the mean +/- 2 SD of controls. All of 8 infected hamsters secreted increased amounts of IL-1 at 4-8 weeks. The mean was 164 (range 17-370) pg IL-1/10(6) mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 micrograms/ml, produced 172.5 ng TNF and 44.6 pg of IL-1/10(6) mononuclear cells/24 hr. The effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages. Significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection, respectively. By 5 weeks, the food intake of infected animals was 46% that of controls. Syrian hamsters infected with L. donovani provide an excellent model with which to study the mechanism of wasting. PMID- 2267968 TI - An improved serodiagnostic procedure for visceral leishmaniasis. AB - The enzyme-linked immunosorbent assay (ELISA) is a sensitive and specific serodiagnostic method for leishmaniasis. In this report, we describe how this versatile assay can be improved by the use of protein A or protein G conjugates for the specific detection of Leishmania antibody in the sera of patients with visceral leishmaniasis. In direct comparisons with anti-immunoglobulin conjugate, enzyme-linked protein A gave significantly higher absorbance values for positive sera without a corresponding increase in absorbance values for sera from normal individuals or from patients with other diseases known to cross-react with leishmaniasis. The effect was to increase the distance between positive and negative values, which aided in the interpretation of the results. This also permitted visual distinction between positive sera and negative or weakly reactive sera. The assay was effective using either blood or serum as the source of primary antibody. A further advantage of protein A over anti-Ig conjugate was its ability to detect specific antibody in dog as well as human sera. Finally, we demonstrated the usefulness of the protein A ELISA with a recombinant leishmania antigen, gp63. PMID- 2267970 TI - Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus. AB - This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted. PMID- 2267971 TI - Small heat shock proteins distinguish between two mosquito species and confirm identity of their cell lines. AB - We have adapted Aedes aegypti cells to Eagle's minimal medium containing nonessential amino acids, glutamine, and 5% fetal bovine serum. In this medium, cells maintained at 28 degrees C under a 5% CO2 atmosphere had a doubling time of 42 hr. Ninety-three percent of the cells in a typical population contained 6 full size chromosomes and an apparent chromosome fragment. Ae. aegypti cells could be distinguished from Ae. albopictus cells by the sizes of the small heat shock proteins, whose synthesis was induced by a brief treatment at 41 degrees C. Analysis of the small heat shock proteins synthesized by dissected ovaries from Ae. aegypti and Ae. albopictus confirmed the species of origin of the 2 cell lines. PMID- 2267972 TI - Transmission of Rift Valley fever virus by adult mosquitoes after ingestion of virus as larvae. AB - We studied the ability of Culex pipiens, Aedes circumluteolus, and Ae. mcintoshi, exposed as larvae to liver tissue from a Rift Valley fever (RVF) virus-infected hamster, to become infected and transstadially transmit virus to the adult and for the adults to transmit virus by bite to hamsters. After exposure as larvae, 9% (5/54) of adult Cx. pipiens and 8% (38/505) of the adult Ae. (Neomelaniconion) species were infected. All of the infected Cx. pipiens and about half of the infected Ae. circumluteolus and Ae. mcintoshi tested transmitted RVF virus by bite to hamsters. Transmission rates for mosquitoes orally infected as larvae were higher than those for mosquitoes orally infected as adults. Animals infected with RVF virus may abort or die in the vicinity of mosquito larvae breeding habitats and infected tissue from these animals may contaminate the water. PMID- 2267973 TI - [Criteria for the antenatal diagnosis of chronic fetal hypoxia in certain forms of high-risk pregnancy]. AB - The author aimed to compared and simultaneously interpret results from cardiotocographic, ultrasound and hormonal studies and to establish objective criteria, showing the degree of antenatal risk for the fetus. She investigated 176 pregnant women with EPH--gestosis, 136 women with chronologically prolonged pregnancy and 50 healthy pregnant women as a control group. Non stress test (NST, functional oxytocin test, quantitative and semiquantitative evaluation of cardiac frequency of the fetus (CFF) were made. Placental structure was examined by an echograph, as well as the amount of amniotic fluid. Fetal biometry was made as well. Total estrogens (TE) were determined in 24-hour diuresis. It was established that the normal curve of NST was a sign of fetal well-being, but that curve combined with deceleration, together with low values of TE, were criteria for reduced compensatory possibilities of the fetus. NST with decelerations in Braxton Hicks contractions, even part greater than 80% and "terminal" or sharply falling values of TE were signs impending fetal death. PMID- 2267974 TI - [Pathological positioning of the placenta at 20 weeks' gestation--its significance for the course of the pregnancy and labor]. AB - The authors found pathologically located placenta in 5.2% of pregnant women during ultrasound examinations at 20 weeks' gestation. The pregnant women were examined periodically by the echograph every 4 weeks. Hundred women with normal localization of the placenta were included in the control group. There were 5 fold more frequent bleedings in the investigated group as 86.5% of bleedings were manifested for the first time after 20 weeks' gestation. The frequency and strength of bleedings were in close connection with the gravity of the pathological insertion. Asymptomatically progressing pregnancies with abnormally localized placenta were 66%. The authors found percentage dependence of pathological placental localization on the gestational period and the possibility for reliable diagnosis. They recommend follow-up of placental localization dynamically till the end of pregnancy on the basis of the possibility for a change in placental localization and its significance for the course of pregnancy and delivery. PMID- 2267975 TI - [Vaginal delivery after 2 and more cesarean sections]. AB - Eight women with deliveries after undergone two and more cesarean section are described. Delivery occurred vaginally in 6 of them, but cesarean section was performed in two of them, whose indications were diagnosed after full dilatation of the cervical canal because of nonadvancement of delivery. A review of literature on this question is presented. Taking into consideration the literary data and their own observations an opinion is expressed that there is basis for a change in the present management of pregnant women with two and more undergone cesarean sections and is proposed to accept the concept for "trial of labor"- evaluation of the cases for vaginal delivery and those for elective cesarean section, taking into consideration criteria for delivery after cesarean section. PMID- 2267976 TI - [The morphological findings in the myometrial arteries and in the placenta with reference to the age of primaparae]. AB - The authors investigate primiparous women at various ages, searching for eventual changes in uterine blood vessels and in the placenta, which eventually could have unfavourable effect on the fetus. The study established progressive thickening due to fibrosis of the muscular layer of the myometrial arteries (in reduction of smooth muscular elements) as well as delay of maturation and differentiation of placental villi with advancement of age of the pregnant woman. These phenomena independently could be the cause for more frequent unfavourable outcome of pregnancy in elderly pregnant women. PMID- 2267977 TI - [Vaginal echography in extrauterine pregnancy]. AB - Twenty eight women with suspicion for extrauterine pregnancy were examined by a vaginal transducer. Extrauterine pregnancy was diagnosed in 18 of them, which was confirmed at the operation. There were no echographic data for tubal pregnancy in 10 of the women. Their further follow-up rejected the presence of extrauterine pregnancy. Three tubal pregnancies were discovered by routine monitoring of ovarian cycles. The immediate proximity of the vaginal transducer to the examined organs in the pelvis gives a possibility for exact topical diagnosis. PMID- 2267979 TI - [The characteristics of the blood anticoagulation system and of urinary fibrinolysis in healthy newborn infants]. AB - An ontogenetic study of parameters of anticoagulative and fibrinolytic system in the blood and urine was carried out on 56 healthy newborn infants at the age of 3 to 28 days. The obtained data and the performed correlation analysis of the coagulative system showed that there was acceleration of fibrinolysis in blood on the background of increased antiplasmatic activity of the blood, RKFM and the concentration of fibrinogen B in blood plasma; the inhibitory activity of the urine, fibrinolytic activity of the urine and the content of PDF in urine were reduced in comparison with the same parameters in older infants. Maximal statistically significant correlation dependences were established during the first week of life of newborn infants. The obtained data could be used as controls in studying various pathological states, connected with changes in coagulative and anticoagulative systems. PMID- 2267978 TI - [Uterine contractile activity in the postoperative period depending on the type of anesthesia]. AB - The functional state of the uterus was studied on 75 parturients, divided into the following groups: a control group of 20 women with normal delivery, first group of 35 parturients with cesarean section anaesthetized by the method of ataralgesia and second group of 20 parturients with cesarean section anaesthetized by the method of neuroleptanaesthesia. The level of the enzyme oxytocinase was determined in sera of parturients. Contractile activity of the uterus during the postoperative period did not depend on the type of anaesthesia. It was established statistically significantly (p less than 0.05) that the combination (metacine, dimidrol, droperidol and phentanyl)--second group, had inhibitory effect on the efficient and rhythmic activity of the uterus in comparison with parturients of the first group (alcosine, diazepam and phentanyl). PMID- 2267980 TI - [Metastasis in patients with uterine tube carcinoma]. AB - Lymphogenic, hematogenic and implanted metastases in 10 women with carcinoma of the uterine tube, treated at the gynecological clinic of the National Oncological Center for the period of 1977-1988, were described. The patients were of the age of 44 to 65 years. Lymphogenic metastases were discovered in: iliac lymph nodes (l. n.) in 4 women, inguinal l. n.--in 2 patients, supraclavicular l. n. in 1 woman and paraaortic l. n.--in one woman. Metastases were found on the anterior abdominal wall in 3 patients, but in two cases in ovaries, omentum, liver, lung. They were discovered in other abdominal organs in single cases. Metastases occurred from 5 months to 8 years since the onset of the disease. Eight patients died from 1 to 3 years after establishment of metastases, but 2 women continued treatment for 2 and 3 years respectively. PMID- 2267981 TI - [The diagnosis, management and treatment results in patients with carcinoma in situ of the cervix uteri]. AB - The authors analysed the results of 225 women with carcinoma of the uterine cervix, treated at the gynecological clinic of the National Oncological Center for a 10-year period. The mean age was 36.7 years. No complaints were found in 206 patients. Cytological Pap 3-5 was established in 221 women. Conformity between histological examination after a colposcopic-directed biopsy, conization or total hysterectomy was found in 117 patients (53.18%). Carcinoma was discovered at 0 degree in 34 patients (11.44%) only just after conization, but in 69 women the tumour was removed during a colposcopic-directed biopsy and was not found in the operation material. Treatment of 217 women was conization, of 3 women--classical total hysterectomy and of 5 patients--intracavitary brachytherapy. In 7 patients the tumour was not removed till healthy tissue, which caused reconization in one woman and total hysterectomy in 6 patients. A relapse of the disease was found in 9 patients up to 2 years after conization (6 cases with carcinoma in situ, 3--with microinvasive carcinoma). Total hysterectomy was performed in all patients. Possibility for discovery of a relapse in the form of invasive carcinoma is ruled out during systemic and continuous observation. It is possible to perform reconization in women with persistent carcinoma in situ in view of preserving their generative function. PMID- 2267982 TI - [The diagnostic and therapeutic results in carcinoma of the cervix uteri]. AB - The study was carried out on 584 women with carcinoma of the uterine cervix, hospitalized and treated at the gynecological clinic of the Higher Medical Institute in the town of Pleven for a period of 9 years (1980-1983). The mean age of the patients was 48.26 +/- 13.31 years. The hospitalized women had 2.25 +/- 0.92 deliveries and 1.87 +/- 0.69 abortions. Investigating premorbid background of the patients, the authors studied frequency and character of the most frequently encountered operative interventions--appendectomy, herniotomies, cholecystectomies, ectopic pregnancy, ulcer, which did not show special differences from the remaining population. Adenocarcinoma of the uterine cervix had, 1.34% of the women and was found more rarely in comparison with some literary data. A 5-year survival was 61.05% of the cases with established metastases and undergone treatment. The mean age of women, in whom the operation of Wertheim was made, was 35 +/- 4.52 years, but that of those with combined x rays therapy was 62 +/- 15.49 years. Possibilities for finding carcinoma of the uterine cervix at early stages of development, according to the authors, depend to a large degree on the oncological training of gynecologists, organization of cytological examinations and exact usage of the results from colposcopic and morphological investigations. PMID- 2267983 TI - [Defloration (a sociomedical study)]. AB - Object of the study were 100 women at fertile age, who informed retrogradely for events connected with disturbance of their virginity. It was established that defloration occurred not at exactly determined moment of the age of young women and girls, but at wider age interval from 16 to 20 years, during noon hours and at night, with equal probability during all seasons, excluding summer, when probability is twice as large, in various places: lodgings, in another's flats, during trips or youth brigades, duration of sexual prey is described, usage of alcohol, ect. An attempt is made to characterize the first partner and stability of the connection between partners, evolution of this connection, which is the background of defloration. The obtained data are compared with data on analogous studies in some other countries. The inferences are proposed as recommendations, which should be taken into consideration by parents, teachers and health services. PMID- 2267984 TI - [Sexual violence as a sociomedical problem]. AB - A review is made on data, described in the literature, in respect to frequency and significance of sexual abuse. In spite of the scarcity of data and discretion, with which the problem is surrounded, it could be determined that in some countries around 10 to 25% of women at mature age run a risk of sexual abuse. The forms are described, in which this violation of sexual freedom of the personality are manifested: abuse, combined abuse and "passive" form of sexual abuse (s refusal of sexual contact in family partners). Data are given on the characteristic of the abuser and his victims. Sexual abuse is connected with individual constitutional factors: character, biorhythms of sexual needs, physiological states leading to frigidity or impotence as well as socially determined factors: education, usage of alcohol, crimogenic environment, ect. In the end a review is made on the measures, which are taken in various countries in the struggle with sexual abuse: legal protection, institutions for recovery of victims of abuse, "hot telephone lines" social measures, etc. PMID- 2267985 TI - [Our experience with the antenatal ultrasonic diagnosis of bilateral polycystic kidney disease]. AB - After a brief review on etiology, pathogenesis, frequency, forms and methods for diagnosis, the authors describe their experience in antenatal diagnosis of fetal bilateral multicystic renal disease. Three cases with this disease are reported, diagnosed before delivery with characteristic differential diagnostic criteria. Possibilities for interruption or reaching full-term pregnancy with the described anomalies of the fetus. PMID- 2267986 TI - [The problems of vaginal candidiasis. II. Protective mechanisms and the role of laboratory diagnosis]. PMID- 2267987 TI - [A case of severe Mendelson's syndrome in cesarean section]. PMID- 2267988 TI - [Cancer of the endometrium and a gigantic intraligamentous myoma--complications and problems]. PMID- 2267989 TI - [A case report of uterine hemorrhage following the insertion of the Medusa intrauterine contraceptive device in the presence of uterine adenomyosis]. PMID- 2267990 TI - [The clinical trial and use of the preparation Palin in urogenital infections]. PMID- 2267991 TI - Dual publication and manipulation of the editorial process. PMID- 2267992 TI - The cutaneous pathology of atopic dermatitis. AB - Sixteen skin biopsy specimens from early eruptive, evolving papules and well developed plaques were obtained from eight patients with established atopic dermatitis. We found that the chronological and histopathological sequence begins with a perivascular interstitial spongiotic dermatitis, evolves into a psoriasiform microvesicular spongiotic dermatitis, which is sometimes focally lichenoid, and eventually concludes as a psoriasiform dermatitis. Thus, atopic dermatitis has characteristic and diagnostic histopathologic findings. These are portrayed and contrasted to what has been previously reported. PMID- 2267993 TI - The enigmatic eccrine epithelioma (eccrine syringomatous carcinoma) AB - Eccrine epithelioma is an exceedingly rare cutaneous tumor thought to represent the malignant counterpart of the eccrine dermal syringoma. To data, only 10 accepted cases appear to have been reported. Two additional cases are described here and the literature is reviewed. The first case showed the typical histologic features of eccrine epithelioma. The second case showed extensive clear cell change (due to glycogen accumulation), reminiscent of the clear cell syringoma; conspicuous pseudo-apocrine metaplasia was also noted. The latter appearance has not been previously described in eccrine epithelioma. PMID- 2267994 TI - Estrogen receptor status in malignant melanoma. AB - Estrogen receptor (ER) positivity demonstrated in malignant melanomas by histochemical and biochemical assays suggested the possibility of hormonal management and improved prognosis as for breast carcinoma patients. We studied the ER status of 5 primary and 28 metastatic malignant melanomas with a commercial immunohistochemical kit (ER-ICA monoclonal), that utilizes monoclonal anti-ER and a peroxidase-antiperoxidase technique, and by a histochemical method using fluorescein-conjugated estradiol (Fluoro-Cep Estrogen assay), on frozen sections. In addition, we conducted a biochemical assay [dextran-coated charcoal cytosolic assay (DCC)] in 16 cases. All 33 cases were ER negative by ER-ICA and Fluoro-Cep: 11 biochemical assays were negative (less than 3 fmol ER/mg protein), four were in the borderline range (3 to 10 fmol ER/mg protein), and one was positive (greater than 10 fmol ER/mg protein) at 11 fmol. The melanomas in 97% of the cases we studied were ER negative by two or three different assays. Low-level estrogen binding of MM tissues may be the result of interactions other than with Type I true ER. The low frequency of ER positivity of malignant melanomas appears to preclude the clinical use of ER status as an indicator for response to hormonal manipulation in patients with malignant melanoma. PMID- 2267995 TI - Chemical warfare casualties and yperite-induced xerodermoid. AB - Chemical warfare agents have been used in recent conflicts. We present a review of the clinical manifestations of mustard gas casualties and we studied the histological presentation of cutaneous lesions. Four groups of alterations were recognized, namely (a) alterations of keratinocytes, (b) epidermal hyperplasia with or without atypia, (c) alterations of the melanocytic system, and (d) structural changes of the dermis. PMID- 2267997 TI - Splenosis. A report of subcutaneous involvement. AB - We report a case of subcutaneous splenosis in the abdominal wall of a 38-year-old woman who had suffered splenic trauma 30 years earlier. A review of the literature shows only five previous cases with subcutaneous involvement. PMID- 2267996 TI - Necrobiotic xanthogranuloma with IgA paraproteinemia and extracutaneous involvement. AB - Numerous nodular xanthomatous lesions arose, gradually increasing in number on the back, chest, lips, tongue, and exposed "V" area of the chest on a 78-year-old man. Painful oral nodules and hoarseness developed subsequently. Histologic examination of the skin revealed a suppurative and granulomatous inflammation with an accumulation of acute polymorphonuclear neutrophils, nuclear dust, and xanthomatous histiocytes. Giant cells were rare and cholesterol clefts were absent. Biopsy of the oral mucosa and the larynx showed a similar process. Direct immunofluorescence was positive for vascular immune reactants at the basement membrane and fibrin in between collagen bundles. The patient had a serum IgA level of 432 mg/dl (normal level, up to 380), with normal IgG and IgM serum concentrations. A Raji cell assay was 240 micrograms/AHGEQ/ml (normal less than 5). CH-50 was decreased and C2, C4, and C3 were within normal limits. The dermatopathology was initially thought to be consistent with erythema elevatum diutinum, and the patient was treated with dapsone and prednisone, with a marginal response. There were no dermatopathologic findings of vasculitis. On review, the patient's dermatopathology was more consistent with necrobiotic xanthogranuloma (NXG). To our knowledge, this is the first report of an association of NXG with an IgA gammopathy and the second reported case of extracutaneous involvement with NXG. PMID- 2267998 TI - Primary culture of cells arising from a neuroendocrine skin carcinoma. AB - A carcinoma arising in the skin of the lip metastasized to the lymph nodes in the neck of a 53-year-old white man. Electron microscopy of the initial excisional biopsy specimen revealed that the tumor cells contained dense-cored vesicles (100 nm in diameter) in their cytoplasm and were joined by simple junctions. Cells from the nodal metastases were found to be immunoreactive for neuronspecific enolase, keratin intermediate filaments, and chromogranin A, but not for neurofilaments. The tumor was thus classified as a neuroendocrine skin carcinoma. In addition, its metastatic cells shared immunoreactive and ultrastructural characteristics of Merkel cells, which are situated in the basal epidermis of normal skin. Primary cultures from a nodal metastasis were established and characterized. The cells attached and proliferated on culture flask surfaces. The population-doubling time was 2 days. This is the first report where cells from a neuroendocrine skin carcinoma have been demonstrated to retain their characteristic ultrastructure in an in vitro environment (10 days). Studies of cells cultured from neuroendocrine skin carcinomas may prove useful in understanding the pathobiology of this disease and help define the in vitro growth requirements of nontransformed Merkel cells as well. PMID- 2267999 TI - A vase-like shape characterizes the epidermal-mononuclear cell collections seen in spongiotic dermatitis. AB - Collections of mononuclear cells are seen within the epidermis in both mycosis fungoides and spongiotic dermatitis. Criteria have been proposed to differentiate between such Pautrier microabscesses or collections, and thier spongiotic mimics. We noted that the collections often assume a vase-like shape when spongiosis is present, with the lips of the vase situated at the interface between granular and cornified layers. Vase-shaped collections were present in five of 49 consecutive biopsy specimens of spongiotic dermatitis, but in none of 50 specimens of mycosis fungoides. These collections can, however, be seen in mycosis fungoides when pronounced spongiosis is present and should be considered as a marker of the process, spongiosis, rather than being diagnostic of spongiotic dermatitis. PMID- 2268000 TI - The language of dermatology and dermatopathology from Robert Willan to A. Bernard Ackerman. AB - Contemporary dermatologists often use sophisticated, striking forms of communication in the exposition of their ideas. Among their innovative techniques is the pseudodialogue, which permits them to summarize and attack the arguments of other researchers while at the same time asserting their own views. Earlier generations of dermatologists were well aware of the need for appropriate and even unconventional linguistic techniques. We contend that the current notion on the part of linguists that scientific language rigidly conforms to certain patterns-for example, the idea that scientific style is essentially impersonal-is much in need of revision. Indeed the conventions have been broken for centuries by leading dermatologists, often deliberately and consciously. PMID- 2268001 TI - Frederick Golomb, M.D. PMID- 2268002 TI - The limits of morphology. PMID- 2268003 TI - What are nevus cells? PMID- 2268004 TI - Sophie's voice, Rorschach's choice. PMID- 2268005 TI - Muscle relaxants in paediatric anaesthesia. A symposium. Proceedings. PMID- 2268006 TI - Neuromuscular blocking agents in paediatric patients: influence of age on the response. AB - This paper reviews the studies in which neuromuscular blocking drugs were compared in at least two different age groups of patients. Most recent studies have lead to a uniform concept of the variation of the effect of these drugs in different age groups. In general, the dose of a nondepolarizing agent required to produce a particular degree of relaxation is similar in neonates (less than one month), infants (one to twelve months) and adolescents (more than thirteen years). However, in children from three to ten years the dose is significantly greater. The maximal effect is reached more quickly in neonates and infants than in the older children and adolescents. These results can be explained by changes in sensitivity, distribution volume and muscle mass. The duration of effect of a nondepolarizing agent is significantly altered by age only in the case of vecuronium, which has a prolonged action in neonates and infants. Suxamethonium remains as the agent with the most rapid onset. PMID- 2268007 TI - Dose response of alcuronium and d-tubocurarine in infants, children and adolescents. AB - Seventy neonatal to adolescent general surgical patients were studied to create an individual dose-response curve for the long-acting neuromuscular blocking agents, alcuronium and d-tubocurarine. The mean (SEM) ED95 of alcuronium was 196 (9), 271 (13) and 243 (8) micrograms/kg in infants, children and adolescents, respectively (P less than 0.01). d-tubocurarine showed a similar age dependent dose-response relationship. ED95 doses were 414 (40), 499 (41) and 445 (31) micrograms/kg, respectively. The onset time (time from intravenous administration to maximal effect) following equipotent dosages was 40-50% shorter in infants than in children or adolescents (1.5 vs 2.7 minutes, P less than 0.05). PMID- 2268008 TI - Maintenance requirement of alcuronium in paediatric patients. AB - Seventeen paediatric patients from 0.3 to 19 years old were studied to determine the individual dose-response curves and the maintenance requirements of alcuronium during N2O-O2-opioid anaesthesia. Alcuronium 300 micrograms/kg maintained the mean (SD) neuromuscular block at 90-95% for 62 34 min). This time was longest in patients of less than 1 year of age (92 min). The hourly maintenance requirement of alcuronium was 0.41 (0.12) times the individual ED95 dose. This value was comparable in infants, children and adolescents and indicates similar duration of effect of alcuronium in all paediatric age groups. PMID- 2268009 TI - Dose-response characteristics of pancuronium in neonates, infants and children. AB - This paper presents pharmacodynamic data for pancuronium in neonates, infants, children and adolescents during N2O-O2-fentanyl anaesthesia. Neuromuscular block (NMB) was evaluated by the adductor pollicis electromyogram. Dose-response curves of pancuronium were parallel in all age-groups. ED95 was greatest in children and least in infants (93 vs. 66 micrograms/kg, P less than 0.05). The rate of spontaneous recovery following 95% NMB was comparable in all age-groups, as was the maintenance requirement of pancuronium when related to ED-values. The hourly requirement to maintain NMB greater than 85% was 60-68% of the individual ED95 dose. When administered on this basis, pancuronium is an equally long-acting neuromuscular blocking agent in patients of all ages. PMID- 2268010 TI - Myasthenia gravis in children and its anaesthetic implications. AB - Myasthenia gravis, a rare disease in children, occurs in a variety of forms. The aetiology and clinical presentations are reviewed. Eight patients who were studied with electromyography are presented. The results show that, in general, patients with the usual pattern of disease are resistant to suxamethonium (ED95 3 4 times normal) and are sensitive to nondepolarizing relaxants. When the latter are used it is advisable to administer small increments with neuromuscular monitoring. One patient with the disease localised to the eyelid had normal EMG responses when monitored on the hand with ulnar nerve stimulation. PMID- 2268011 TI - Suxamethonium--electromyographic studies in children. AB - Suxamethonium was administered to 225 children aged from one to sixteen years, in doses varying from 0.1 to 0.5 mg/kg. Dose responses were determined. ED95 was 445 micrograms/kg in one to four year olds, 454 micrograms/kg in the five to ten years group and 270 micrograms/kg in eleven to fifteen year olds (P less than 0.05). There is a wider variability in patient responses to 0.1 and 0.2 mg/kg than to the higher doses. Sixty-two children in the three age groups were given suxamethonium 1 mg/kg. The time from injection to maximum block and to 50% recovery increased with increasing age (P less than 0.05). PMID- 2268012 TI - Responses to small doses of suxamethonium in four children with abnormal cholinesterase--a case report. AB - Four patients with genetic cholinesterase abnormalities were studied with electromyography after being given suxamethonium 0.1 mg/kg. An abnormal homozygous patient was paralysed for 17 minutes. The duration of response in heterozygous patients was 2-4 minutes, being shorter when cholinesterase activity levels were near normal. PMID- 2268013 TI - Does suxamethonium influence the subsequent dose requirements of alcuronium and its reversibility in children? AB - Suxamethonium is often used for intubation prior to the use of a nondepolarizing muscle relaxant. This study was performed to determine whether suxamethonium altered the dose of alcuronium required to produce neuromuscular block. The findings were that suxamethonium 1.0 mg/kg did not alter the depth, duration or reversibility of block if given before alcuronium 0.3 mg/kg. Reversal with neostigmine was more rapid following 50 micrograms/kg than after 25 micrograms/kg. If recovery from neuromuscular block was greater than 25 per cent, the lower dose produced satisfactory reversal, whether or not suxamethonium had been given previously. PMID- 2268014 TI - Alcuronium requirement in patients receiving phenytoin--a case report. PMID- 2268015 TI - Simultaneous monitoring of force, acceleration and electromyogram during computer controlled infusion of atracurium in sheep. AB - Five sheep were anaesthetised with sodium thiopentone, nitrous oxide and oxygen, and the lungs ventilated artificially. A computer-controlled infusion of atracurium employing feedback from isometric force measurement was set to maintain 15, 50 and 85% depth of neuromuscular block. Each was held constant for 30 minutes, while isometric force and electromyogram were measured on the left forelimb and acceleration on the right. The acceleration transducer records at the three levels of block were practically identical with those from force measurements: mean differences (SD) between simultaneous measurements being 3.6 (5.4)%. EMG value was 10.1 (12.0)% different from force measurement. Correlation between simultaneous force and either acceleration or EMG was excellent (r = 0.986 and 0.938 respectively). In clinical practice all three techniques measure block comparably. In the sheep forelimb, EMG was a less reliable method of measuring block. PMID- 2268016 TI - Accurate monitoring of neuromuscular blockade using a peripheral nerve stimulator -a review. AB - For normal anaesthetic practice, monitoring of neuromuscular blockade is best performed by stimulation of the ulnar nerve at the wrist with a peripheral nerve stimulator and evaluation of the response of the thumb. Determination of the initial threshold for stimulation in the awake patient to allow estimation of the current required for supramaximal stimulation is an important set-up procedure to improve accuracy. The degree of paralysis of specific muscle groups such as the diaphragm can be inferred from their sensitivity to neuromuscular blocking agents relative to adductor pollicis. Monitoring with different stimulation patterns allows a wide spectrum of muscle paralyses to be evaluated. PMID- 2268017 TI - Hypoxaemia during postoperative recovery using continuous pulse oximetry. AB - Continuous pulse oximetry monitoring was used to determine the incidence of hypoxaemia (arterial oxygen saturation less than or equal to 90%) occurring in the first hour of postoperative recovery. Of 107 patients studied, hypoxaemia was recorded in 80%. Twenty-eight (26%) of these patients had saturations below 80%. The average frequency (i.e., the number of desaturations per patient) and the total duration of these desaturations was 7.7 desaturations and 182 seconds respectively. Intermittent measurements taken preoperatively and at 5 and 30 minutes postoperatively revealed hypoxaemia in 2%, 4% and 6% of patients respectively. In 39 patients who received oxygen therapy throughout the monitoring period, 64% experienced hypoxaemia within the first 15 minutes of recovery as opposed to only 18% in the final 15 minutes monitoring period. Of the factors assessed, only patients with a body mass index greater than 25 had an increased risk of hypoxaemia (P less than 0.01). Four patients required active intervention and ventilatory assistance. We conclude that postoperative hypoxaemia is a particularly common occurrence even in patients otherwise considered healthy. Hence, pulse oximetry should be employed routinely during recovery. Where possible, monitoring should be performed continuously for at least 45 minutes. PMID- 2268018 TI - Oxygen saturation during general anaesthesia and recovery for outpatient oral surgical procedures. AB - Various factors have resulted in an increased demand for relatively minor surgical treatment requiring general anaesthesia to be carried out in the surgery on an outpatient basis. Previous studies have reported significant decreases in oxygen saturation in patients under intravenous sedation and in patients under general anaesthesia. This study examined the levels of oxygen saturations in outpatients undergoing oral surgical procedures under general anaesthesia. The results confirm the value of pulse oximetry and suggest that this mode of monitoring and the administration of supplemental oxygen be routinely utilised during the recovery period. PMID- 2268019 TI - Unlimited clear fluid ingestion two hours before surgery in children does not affect volume or pH of stomach contents. AB - To determine the effect on gastric contents of unlimited clear fluid ingestion by children up to two and a half hours and then up to two hours before elective surgery, 228 healthy children (ages two to twelve years) were prospectively studied. During Phase I of this study subjects ingested unrestricted volumes and types of clear fluids up to three hours (control group) or two and a half hours before surgery. After establishment of adequate anaesthesia, gastric fluids were aspirated via an orogastric tube. Gastric volume was measured with a syringe and gastric pH was determined. After determining that there was no adverse effect associated with reducing a clear fluid fast to two and a half hours, Phase II of the study was begun. The methods for Phase II were unchanged except that unlimited clear fluids were permitted up to three hours (control group) or two hours preoperatively. In both Phase I and II, gastric volume and gastric pH were unaffected by reducing the fast to less than three hours. It is concluded that ingestion of unlimited clear fluids up to two hours before elective surgery does not affect gastric contents of healthy children. PMID- 2268020 TI - A study of preoperative fasting in infants aged less than three months. AB - The effects of preoperative fasting on plasma glucose and gastric emptying was studied in 62 infants aged less than three months after a feed of either breast milk or an infant milk formula. Prior to induction of anaesthesia no infant was hypoglycaemic, defined as plasma glucose less than 2.2 mmol/l. Five per cent of infants had a significant volume of residual gastric contents. The mean intraoperative plasma glucose levels rose significantly and this was not influenced by the use of intravenous Hartmann's solution or low dose opioids. Infants in this age group tolerate three- to four-hour preoperative fasts well as no infant became hypoglycaemic intraoperatively. They demonstrate a hyperglycaemic response to the stress of anaesthesia and surgery, and may not need routine intraoperative glucose supplements although plasma glucose should still be monitored. PMID- 2268021 TI - The addition of fentanyl to epidural bupivacaine in first stage labour. AB - Epidural analgesia was studied in 100 healthy Chinese women with uncomplicated pregnancies in first stage labour. Patients were randomly allocated to receive 8 ml of one of the following five solutions: bupivacaine 0.125% with fentanyl 50 micrograms or fentanyl 100 micrograms, bupivacaine 0.25% plain, bupivacaine 0.25% with fentanyl 50 micrograms or fentanyl 100 micrograms. There was no difference in quality of analgesia among groups as measured by the reduction of visual analogue pain scores 20 minutes after the epidural dose. The duration of analgesia was similar among groups with the overall median duration being 105 minutes. There was no difference in method of delivery or neonatal Apgar scores. The least concentrated mixture providing good quality analgesia for the first stage of labour was the combination of bupivacaine 0.125% with fentanyl 50 micrograms. PMID- 2268022 TI - Positioning central venous catheters--a prospective survey. AB - This paper reports the results of a prospective survey of 266 attempted central venous catheterisations by various routes, evaluating their success rate and incidence of immediate complications and attempts to demonstrate a relationship between patient height in centimetres (H) and ideal catheter length. The overall rate of intrathoracic placement was 230 from 239 catheterisations (96%) after 266 attempts (86%). Of these 230 catheters, 54 terminated in the right atrium (24%). To avoid right atrial placement with its well documented risk of cardiac tamponade, it is recommended that right infraclavicular subclavian catheters are inserted to H/10-2 cm, right internal or external jugular catheters to H/10 cm and left external jugular catheters to H/10 + 4 cm. PMID- 2268023 TI - A comparison of intravenous cannulae available in New Zealand. AB - This study examined physical and clinical features of eleven models of disposable intravenous cannulae available in New Zealand: Angiocath, Braunule, Insyte, Jelco, J.M.S., Medicut, Nipro, Quikcath, Surflo, Venflon and Wallace. Dimensions of external and internal diameter and wall thickness varied greatly among the models of the same gauge size. As a result, flow rates also varied greatly, but linearly with internal diameter. Anaesthetists were randomly given a range of 16 and 22 gauge cannulae for routine clinical use (forty of each model) and completed a questionnaire on features of cannula performance relating to success of cannulation, ease of insertion, ease of handling, kinking, and packaging. The results of this questionnaire are presented and discussed. The 22 gauge cannula tips were assessed microscopically for distortion after clinical use. Jelco cannulae were found to have the highest incidence of catheter tip distortion (54%). PMID- 2268024 TI - The stability of atracurium in clinical practice. AB - Atracurium has an unusual intrinsic Hofmann elimination which is increased by an alkaline environment and increased temperature. Normally the relaxant is stored at pH 3.3 and kept at a temperature of 4 degrees C. However, it is convenient to have a reasonable quantity available within the operating theatre. This study examined the rate of degradation of atracurium in the operating theatre environment of 20 degrees C. Atracurium within one month of its expiry date was placed in the drawer for anaesthetic drugs in each of three operating theatres. At the end of each month, further drug was added to the stock. At the end of the study, atracurium which had been stored continuously at 4 degrees C, was at 102.9% of nominal strength, having started with 113.5% at manufacture. Atracurium which had been at room temperature for one, two and three months respectively retained 99%, 95% and 92% strength respectively. These results show that even three months' exposure to room temperature does not cause enough deterioration to be clinically significant. PMID- 2268025 TI - Are obstetric spinal headaches avoidable? AB - In a prospective study of one hundred obstetric patients given spinal anaesthesia using either a 25 or 26 gauge spinal needle, a significantly greater incidence of spinal headache and blood patch was found in the 25-gauge group. It is concluded that a 26-gauge needle should be used when performing spinal anaesthetics for obstetric procedures. PMID- 2268026 TI - Rate-controlled analgesia: a laboratory evaluation of a new infusion device. AB - We report an evaluation of the Bard Harvard Mini Infuser, one of a new generation of agent-specific intraoperative infusion pumps which are designed for use by the anaesthetist. This pump permits potent intravenous anaesthetic agents to be used in pharmacokinetically designed dosage regimens. The controls are calibrated directly in kg body weight and micrograms per minute rather than the usual settings of ml of solution per hour. The performance was assessed by measuring the volume delivered over given time intervals and all safety functions were tested at least three times. This device was found to be acceptably safe and accurate. Two points to note are that it must be purged every time before it is connected to the intravenous infusion and if an occlusion is suddenly relieved, the patient can receive an 'accidental bolus' of up to 1.18 ml of drug. The main advantage of this pump is that it uses undiluted drug direct from the ampoule and does not require any calculations or dilutions prior to use. However, this restricts its use to drugs with a concentration of 500 mcg/ml and in effect means that it is suitable mainly for infusion of alfentanil. PMID- 2268027 TI - Critical incidents with nonrebreathing valves. PMID- 2268028 TI - Phaeochromocytoma in a malignant hyperthermia patient under anaesthesia. PMID- 2268029 TI - Dangerous leak. PMID- 2268030 TI - Patient-controlled analgesia--the value of a background infusion. PMID- 2268031 TI - Failure of oxygen flush. PMID- 2268033 TI - Failed extubation due to 'sutured' double-lumen tube. PMID- 2268034 TI - Herniation of RAE tube through split Boyle Davis gag. PMID- 2268032 TI - Tetanus and hypersensitivity to suxamethonium. PMID- 2268035 TI - A new technique for insertion of an intra-arterial cannula. PMID- 2268036 TI - Preoxygenation and facial injuries. PMID- 2268037 TI - 2% lignocaine for spinal anaesthesia. PMID- 2268038 TI - Anaesthesia for colonoscopy. PMID- 2268039 TI - Moyamoya disease. PMID- 2268040 TI - Enalapril and SPPS. PMID- 2268041 TI - Helium-oxygen in laser therapy for bronchial stenosis. PMID- 2268042 TI - Dual airway pathology. PMID- 2268043 TI - Propofol and seizures. PMID- 2268044 TI - A footplate for conventional PCA demand buttons. PMID- 2268045 TI - C-size cylinders. PMID- 2268046 TI - Failure of a spring guide wire. PMID- 2268047 TI - Advantages of PCA exaggerated? PMID- 2268048 TI - To paralyse or not to paralyse; that is the question. PMID- 2268049 TI - Failed intubation at caesarean section--a reply. PMID- 2268050 TI - The clinical chemistry laboratory of the future. PMID- 2268051 TI - Determination of serum uric acid by isotope dilution mass spectrometry as a new candidate definitive method. AB - A new isotope dilution mass spectrometric method for uric acid is described. A known weight of [1,3-15N2]uric acid is added to a known weight of serum, and the mixture is allowed to equillibrate. The serum is put through an anion-exchange resin, and the isolated uric acid is converted to the tetrakis-(tert butyldlmethylsilyl) derivative of uric acid. For measurement, the derivative is injected into a gas chromatograph interfaced with a low-resolution, magnetic sector mass spectrometer. Isotope ratio measurements are made from the abundances of the [M - tert-butyl]+ ions at m/z 567 and 569. Bias is investigated by measuring the uric acid level in the same samples under different chromatographic conditions and with different ionization techniques. If these confirmatory measurements agree with the principal measurements, we have strong evidence for the absence of measurement bias. Uric acid was determined in three lyophilized human serum pools by this method. For Standard Reference Material (SRM) 909, four sets of six samples each were prepared. For Candidate SRM 909a, which consisted of two pools, each with a different level of uric acid, six sets of two samples of each level were prepared. The coefficient of variation for a single measurement ranged from 0.34% to 0.42%, while the relative standard error of the mean ranged from 0.08% to 0.14%. The results from the confirmatory measurements demonstrated that there was no significant bias in the measurements. The combination of high precision and absence of significant bias in the results qualifies this method as a candidate definitive method as defined by the National Committee for Clinical Laboratory Standards. PMID- 2268052 TI - Potentiometric biosensor employing catalytic antibodies as the molecular recognition element. AB - Catalytic antibodies are introduced as an important new class of biomolecules for molecular recognition in biosensors in which the binding sites are continually regenerated by the catalytic reaction of the substrate. Consequently, molecular recognition by catalytic antibodies can yield reversible immunoblosensors. In this example, a prototype potentiometric biosensor is described in which a micro pH electrode is modified with a catalytic antibody that catalyzes the hydrolysis of phenyl acetate, producing hydrogen ions that can be monitored by the electrode. The reversible response is linear with the log of substrate concentration over a range of 20-500 microM with a detection limit of 5 microM under the conditions of this study. Alternative applications of catalytic antibodies in other biosensor configurations are discussed. PMID- 2268053 TI - Transient infrared transmission spectroscopy. AB - Transient infrared transmission spectroscopy is a new method that can acquire analytically useful transmission spectra from moving, optically thick solids. No sample preparation is required. The spectra are of sufficient quality for accurate quantitative compositional analysis. The method works by the creation of a thin, short-lived, chilled layer at the sample surface. Blackbody-like thermal emission from the bulk of the sample is selectively absorbed as it passes through the chilled layer, so the transmission spectrum of the layer is superimposed on the observed thermal emission. Spectra of polycarbonate, beeswax, and copolymers of methyl and butyl methacrylate are presented. Compositional analysis of the methacrylate copolymers with a standard error of prediction of only 0.87 mol % is demonstrated. PMID- 2268054 TI - Integrated optical attenuated total reflection spectrometry of aqueous superstrates using prism-coupled polymer waveguides. AB - Attenuated total reflection (ATR) spectrometry of aqueous solutions in contact with polystyrene integrated optical waveguides has been investigated. The mode dependent absorption of evanescent energy by fluorescein solutions adjacent to the waveguide surface was measured and compared to theoretical predictions based on a ray optics approach. Although enhanced sensitivity was observed with increasing mode number, the sensitivity for the highest order mode was less than that predicted by theory. PMID- 2268055 TI - Ultrastructure of the subpial glial limitans in the cerebellum of the lizard (Lacerta lepida). AB - The subpial glial limitans in the cerebellum of the lizard (Lacerta lepida) is a single layer formed by the extensions of the fibers of Bergmann's glia. These subpial extensions present a prismatic aspect, few organelles and abundant whorls of smooth endoplasmic reticulum. These whorls of endoplasmic reticulum appear as concentric and tubular membranous formations. The glial limitans is not continuous at times. PMID- 2268056 TI - An electron microscopic study of the leptomeninx and associated cells of the aged mouse. AB - The ultrastructure of the leptomeninx was examined in mice aged 25, 28 and 31 months. Apart from occasional lipofuscin granules there were no obvious age related changes in the ultrastructure of leptomeningeal cells. Granular pial cells usually contained large honeycomb bodies and were a prominent feature of the ageing leptomeninx but in contrast leptomeningeal macrophages showed no evidence of phagocytic activity suggesting that cell death or degeneration was not a feature of cells of the leptomeninx even in extremely old mice. PMID- 2268058 TI - Uptake of labelled proline in the degenerating retina of goldfish. AB - A goldfish model with degenerating retina was utilized. Degeneration of inner nuclear layer and ganglion cell layers began prior to degeneration of outer nuclear layer. In these models, the photoreceptors still showed uptake of labelled proline. This indicated that the metabolic activities of the first order neuron was independent to its neuronal linkage with other neurons. PMID- 2268057 TI - [Structural aspects of the walls of the human coronary sinus]. AB - The authors studied the structure and the disposition of the connective-muscular tissue components of the superficial (epicardiac) and deep (myocardiac) walls of the coronary sinus. The connections of the coronary sinus walls to epicardium and myocardium, through septums fibrous of the perimisium, may play the role of increasing the resistence of the walls during the elevation of the venous pression. The presence of voluminous fascicles of circular and oblique cardiac muscle fibers coming from myocardium walls of the atria, that completely turning around the superficial wall of the sinus, to our knowledge, it would act as a functional sphincteric dispositive, able to maintain impulse of blood-stream and even to prevent blood reflux during atrial presystole. The authors, also, presented the structure and the function of the coronary sinus and Vieussens valves. PMID- 2268059 TI - [The morphometry of the ear ossicles in humans during development]. AB - The dimensions and the mass of the auditive ossicles was determined bilaterally in 100 human fetuses, of each sex aged from 21 to 40 weeks and 20 individual adults aged 18 to 40 years. It was found that the development of auditive ossicles in human is not completed during fetal life. The analyzed parameters of malleus (a, b, c, d1, d2, e) in the over fetal life period increased adequately by 14.02%, 11.22%, 16.70%, 12.80%, 12.01%, 21.98%, incus by (a, b, c1, c2, d, e) 7.61%, 11.48%, 11.40%, 23.59%, 12.14%, 14.94%, stapes by (a, b, c, d, e, f) - 6.28%, 7.66%, 8.40%, 4.54%, 4.54%, 4.16%. In the over fetal life period increase of weight of malleus by 22.05%, incus by 26.49%, stapes by 11.57% was also observed. Described parameters of ossicles system are very important with respect to classification to the operations improving hearing in the system convecting of vibration of the tympanic membrane in children. PMID- 2268060 TI - Anatomical variations in the formation of the human oesophageal hiatus. AB - The formation of the oesophageal hiatus was studied in 50 human diaphragms in which crura and the median arcuata ligaments were carefully dissected and their fibres were carefully traced to the central tendon. In 98% of the cases the right crus was divided into a medial, a middle and a lateral bundle. In 90% the left crus was divided into a medial and a lateral bundle. The medial bundle of the right crus was a constant component in bounding the hiatus. The undivided crura did not contribute to the borders of the hiatus. 5 variations in the formation of the hiatus were observed. In 62% the hiatus was bounded by the 2 crura mainly the right; the left crus shared only in the formation of the posterior border. In 10% the 2 crura contributed equally to the formation of the hiatus; the hiatus was formed by the medial bands. In 10% the hiatus was formed exclusively by the right crus. In 2% the hiatus was formed exclusively by the left crus. In 16% crura had no direct relation to the hiatus except posteriorly and the hiatus was bounded by a V-shaped band from the median arcuate ligament, this finding has not been previously reported. The functional significance of these variations was discussed. PMID- 2268061 TI - Palmaris longus muscle substituting for the ring finger slip of flexor digitorum superficialis. AB - An unusual and unrecorded variation in palmaris longus muscle is described. The muscle had a normal appearance and origin from the common tendon arising from the medial epicondyle of the humerus and from the surrounding intermuscular septa. The distal tendon however entered the hand via the carpal tunnel medial and deep to the median nerve, split and inserted into the lateral and medial sides of the middle phalanx of the ring finger. It therefore substituted completely for the slip to the ring finger from flexor digitorum superficials, which was absent. PMID- 2268062 TI - Fibre types of M. pectineus of the cat (Felis domestica). AB - As revealed by the NADH-diaphorase, SDH and myosin ATPase, the M. pectineus of the cat possesses at least 3 main kind of fibres, with different distribution on the superficial and deep portions of the muscle. The superficial portion revealed that 23.6% are FOG fibres: 17.8% are SO fibres and 58.6% are FG fibres. Already the deep portion revealed that 61.4% are FOG fibres: 14.5% are SO fibres and 24.1% are FG fibres. The myosin ATPase reaction was used to demonstrate contracting characteristics. These findings suggest that the movements of fast contraction of M. pectineus are predominant. PMID- 2268063 TI - Abnormal drainage of the middle cardiac vein (V. cordis media). AB - The middle cardiac vein (V. cordis media) which is known to be one of the tributaries of the coronary sinus (Sinus coronarius) is found to open into the left atrium in a 79 years old female cadaver. The ostium is guarded by a semilunar (crescent shaped) valve. PMID- 2268064 TI - Three-dimensional architecture of the connective tissue core of the lingual papillae in the guinea pig. AB - The three-dimensional structure of the connective tissue core (CTC) of the lingual papillae of the guinea pig was studied by means of scanning electron microscopy, after fixation with Karnovsky's fixative and after removal of the epithelial cell layers by long-term treatment with hydrochloric acid. The CTC of four types of lingual papillae was revealed. (a) Filiform papillae distributed over the anterior part (comprising about one half of the tongue) are characterized by having a few long connective tissue protrusions arranged transversely to the long axis of the tongue, while large conical papillae distributed on the intermolar prominence (intermediate part comprising most of the posterior half of the tongue) have more numerous and longer connective tissue protrusions, forming a bundle. (b) Fungiform papillae scattered among the filiform papillae are restricted to the anterior part of the tongue and possess connective tissue components in the form of a "fist-like" structure. (c) Foliate papillae are found in lateral and posterior locations. At both sites they contain slender epithelial crypts. Removal of the epithelia reveals wide grooves which correspond to the epithelial crypts. The rims of these grooves are surrounded by numerous small protrusions. PMID- 2268065 TI - Use of rhodamine 123 to label and lesion interstitial cells of Cajal in canine colonic circular muscle. AB - The role of interstitial cells of Cajal (ICC) is difficult to determine because these cells are not easily identified by light microscopy, and there are no compounds available to specifically lesion ICC. Ultrastructural studies have shown an abundance of mitochondria in ICC. Therefore, we have used rhodamine 123, a fluorescent dye that is specifically accumulated by mitochondria, to identify ICC in canine proximal colon. This technique provided good discrimination between ICC and smooth muscle cells, but enteric neurons were labeled with rhodamine 123. This compound has cytotoxic properties in some cells. Therefore, we treated intact muscle strips with rhodamine 123 while recording intracellular electrical activity from circular muscle cells. Uptake of rhodamine 123 by ICC was associated with an alteration in electrical rhythmicity. These data suggest that rhodamine 123 may be a useful tool for visualizing and perhaps chemically lesioning ICC. PMID- 2268066 TI - The cranial venous system in the rat: anatomical pattern and ontogenetic development. I. Basal drainage. AB - The anatomical pattern and development of the venous system of the cranial base in the rat is described. The anatomy of the venous system was determined from observations of vascular casts in adult rats; the development of the vascular system was established by examination of ink-injected embryos. A transverse sinus system was found to be present in the basal venous system. The sinus connects the posterior facial veins; its middle section transverses the cranial base through the basisphenoid canal, and it receives the venae ophthalmicae within the basisphenoid bone. The venae ophthalmicae in turn are connected to the perioptic veins and to the sinus interperiopticus intracranially. Dorsally, the venae ophthalmicae anastomose with the paired sinus cavernosus. The term sinus transversus basalis is proposed for the venous connection between the posterior facial veins within the basisphenoid bone of the rat. The anlage of the sinus transversus basalis is established by vascular networks during the final prenatal period, its formation, however, is only completed postnatally. The anlages of the venae periopticae, the venae ophthalmicae, the sinus cavernosus and the rami intercavernosi are already established at early developmental stages. The characteristic pattern is formed before birth. PMID- 2268067 TI - The formation of premuscle masses during chick wing bud development. AB - The skeletal musculature of chick limb buds is derived from somitic cells that migrate into the somatopleure of the future limb regions. These cells become organized into the earliest muscle primordia, the dorsal and ventral premuscle masses, prior to myogenic differentiation. Therefore, skeletal-muscle specific markers cannot be used to observe myogenic cells during the process of premuscle mass formation. In this study, an alternative marking method was used to determine the specific stages during which this process occurs. Quail somite strips were fluorescently labeled and implanted into chick hosts. Paraffin sections of the resulting chimeric wing buds were stained with the monoclonal antibody QH1 in order to identify graft-derived endothelium. Non-endothelial graft-derived cells present in the wing mesenchyme were assumed to be myogenic. At Hamburger and Hamilton stage 20, myogenic cells were distributed throughout the central region of the limb, including the future dorsal and ventral premuscle mass regions and the prechondrogenic core region. By stage 21, the myogenic cells were present at greater density in dorsal and ventral regions than in the core. By stage 23, nearly all myogenic cells were located in the dorsal and ventral premuscle masses. Therefore, the two premuscle masses become established by stage 21 and premuscle mass formation is not complete until stage 23 or later. Premuscle mass formation occurs concurrently with early chondrogenic events, as observed with the marker peanut agglutinin. To facilitate the investigation of possible underlying mechanisms of premuscle mass formation, the micromass culture system was evaluated, to determine whether or not it can serve as an accurate in vitro model system. The initially randomly distributed myogenic cells were observed to segregate from prechondrogenic regions prior to myogenic differentiation. This is similar to myogenic patterning in vivo. PMID- 2268069 TI - Association of cephalic neural crest cells with cardiovascular development, particularly that of the semilunar valves. AB - The quail-chick chimera method was used to examine whether neural crest cells were associated with the formation of semilunar valves. From the metencephalon to somite 5, or from the otocyst to somite 3, left, right, or bilateral neural folds, including the neural crest, were transplanted. Among embryos used for the experiment, three into which left neural crest cells were transplanted, two into which right neural crest cells were transplanted, and two into which bilateral neural crest cells were transplanted had a morphologically normal heart. In these embryos, neural crest cells were found in all cusps of the aortic and pulmonary semilunar valves. Although neural crest cells have been thought to have no association with the formation of the semilunar valves, our experiment indicates that such association indeed occurs. PMID- 2268068 TI - The presence of a juxtaglomerular apparatus in elasmobranch fish. AB - Previous studies have concluded that a juxtaglomerular apparatus evolved in phylogenetic groups "higher" than elasmobranch fishes. The present study shows for the first time a distinct juxtaglomerular apparatus in four marine elasmobranchs, the spiny dogfish Squalus acanthias), the smooth dogfish (Mustelus canis), the little skate (Raja erinacea), and the cownose ray (Rhinoptera bonasus). Serial semithin sections of these fishes' kidneys reveal the four morphological components of a juxtaglomerular apparatus at the vascular pole of the renal corpuscle: (1) an afferent arteriole surrounded by smooth muscle cells which have granules containing a material exhibiting a periodic substructure comparable to that of renin granules in higher vertebrates; (2) an efferent arteriole usually devoid of smooth muscle cells but having pericyte-like cells; (3) a macula densa portion of the distal tubule juxtaposed between the afferent and efferent arterioles; and (4) elongated, fusiform cells (Goormaghtigh cells), which are in continuity with similar cells of the abundant intra-glomerular mesangium, and fill the space bordered by the distal tubule and by the afferent and efferent vessels. The distal tubule, from the site where it lies close to the afferent arteriole, moves directly toward the urinary pole, frequently indenting the renal corpuscle. Within this indentation, the tubule may be flanked by the efferent vessel, by the extraglomerular mesangium, or by Bowman's capsule only. Facing these structures the tubular epithelial cells possess basally dilated intercellular spaces. Endothelial cells of the efferent vessel(s) are fenestrated, possessing pores which are closed by a diaphragm. CONCLUSION: marine elasmobranch fish possess the morphological components of a juxtaglomerular apparatus which suggests that these fishes, like most other vertebrates, possess a renin-angiotensin system and a glomerular-tubular feedback mechanism. PMID- 2268070 TI - Multifocal innervation and muscle length. A morphological study on the role of myo-myonal junctions, fiber branching and multiple innervation in muscles of different size and shape. AB - The dependence of the inner organisation and innervation of a skeletal muscle on its size was studied at the level of single muscle fiber architecture and motor endplate topography in muscles of different size, all of them lacking a tendinous scaffolding. The muscles evaluated in this study were: Mm. sternomastoideus, gracilis and latissimus dorsi of the rat and the M. sternocephalicus of the horse. In these muscles a subdivision into two or more 'innervation-compartments' becomes obvious in fascicles reaching a certain length. This provides the possibility of an almost synchronous activation of the entire muscle by its nerve. At the level of single muscle fiber elements, large numbers of myo-myonal junctions were discernible in many sites. However, unequivocal multiple innervation was found, with several end-plates per single muscle fiber, without the interposition of any junctional structure. Myo-myonal junctions, combined with a characteristic branching pattern of many muscle fibers, and scattered innervation sites, obviously play an important role in the architecture of fan like muscles lacking a tendinous scaffolding. PMID- 2268072 TI - DNA fingerprints of chickens selected for high and low body weight for 31 generations. AB - Two lines of White Plymouth Rock chickens that have been divergently selected for 8-week body weight for 31 generations were compared for patterns of DNA fingerprints (DFP). Digestion of DNA with HinfI and hybridization to Jeffreys' minisatellite probe 33.6 resulted in DFPs that were relatively similar within lines (bandsharing = 0.50) and less similar between lines (bandsharing = 0.22). Analyses of scorable DFP bands produced by mixing DNA from individuals within lines indicated that 48% were line-specific. Causes for the differences in DFP patterns between lines and for occurrence of line-specific bands for the two lines divergently selected for body weight are discussed. PMID- 2268071 TI - The human brain at stages 18-20, including the choroid plexuses and the amygdaloid and septal nuclei. AB - The development of the human brain during the seventh embryonic week was studied in serial sections of 88 embryos, and graphic reconstructions were prepared. From stages 18 to 20 the cerebral hemispheres expand rapidly and become more and more distinct entities. The longitudinal fissure between them occupies approximately half of their rostrocaudal extent. In stage 20 they have progressed so far in organization that functional aspects (based on synapses in the primordial plexiform layer) are of importance. An advanced differentiation is also present in the amygdaloid body, which has at least four individual nuclei, and in the forebrain septum, which shows the nucleus of the diagonal band and the medial septal nucleus. This has a bearing on recent experimental studies that document the fundamental role of the septal nuclei with regard to behavioural and cognitive functions. Fibre connections between septal nuclei and hippocampus have appeared. A definitive internal capsule, however, is not yet present. The main connections with diencephalon and other parts of the brain are chiefly by fibres to or from the amygdaloid body by way of the lateral forebrain bundle. The olfactory areas are connected with the habenular nuclei by a well developed stria medullaris thalami. Globus pallidus externus, entopeduncular nucleus, and subthalamic nucleus are prominent features in the subthalamus. The main nucleus of the oculomotor nerve shows a dorsolateral and a ventromedial portion. The rhombic lip is mitotically active in all parts of the rhombencephalon, and seems to participate significantly in the formation of the intermediate layer of the cerebellum and of the cochlear nuclei. The sensory nucleus of the trigeminal nerve has appeared. In the cerebellum the cell layer thought to contain the future Purkinje cells develops. The cerebellar plate is organized into external and internal bulges, and is now connected with mid- and hindbrain through fibre bundles. The area thought to be the dentate nucleus and the supposed floccular region are especially rich in fibres. The accessory olivary nucleus appears in stage 19, and accessory nuclei of the abducent and hypoglossal nerves are evident in stage 20. The choroid plexuses of the fourth and lateral ventricles have appeared. In view of their advanced features, the study of embryos of stages 19 21 becomes increasingly relevant to questions of tissue transplantation. PMID- 2268073 TI - Polymorphism of pig serum alpha-protease inhibitor-3 (PI3) and assignment of the locus to the Pi1, Po1A, Po1B, Pi2, Igh linkage group. AB - Polymorphism of an alpha-protease inhibitor, PI3, in pig serum samples was detected using 2D agarose gel (pH 5.4)--polyacrylamide gel (pH 9.0) electrophoresis. Evidence was obtained that the five variants observed (A, B1, B2, C and D) are under genetic control by codominant alleles (Pi3A, Pi3B1, Pi3B2, Pi3C and Pi3D) at one autosomal locus. Variants A, B1, B2 and C inhibited chymotrypsin; there was no appreciable inhibition of trypsin and papain. Variant D did not inhibit chymotrypsin, and therefore its classification as a PI3 variant was put in question. PI3 typing was not possible in about 50% of the studied pigs since in those cases the PI3 variants were either too weak or absent. On the basis of backcross matings and haplotyping in complete families for protease inhibitor loci Pi1, Po1A, Pi2 and Pi3 it was proved that the Pi3 locus belongs to the protease inhibitor gene cluster, and the position of the locus in the linkage group was proposed as being Pi1-Po1A-(Po1B)-Pi3-Pi2-(Igh1, Igh2, Igh3, Igh4). PMID- 2268074 TI - Salivary gland amylase polymorphism in pigs and cattle detected by affinity electrophoresis. AB - New allelic variants of salivary gland alpha-amylase in pigs (AMY-1C, AMY-1D) have been detected using affinity electrophoresis. In yak, zebu and in hybrids (yak x cattle, zebu x cattle) a new AMY-1 allelic variant (AMY-1D) has been found using the same method. PMID- 2268075 TI - Variation of some serum proteins in red deer, Cervus elaphus L. AB - Various electrophoretic techniques, immunoblotting and inhibitions of trypsin and chymotrypsin were used to study the variability of serum proteins in farmed red deer, Cervus elaphus L., of Czechoslovakian origin. Easily interpretable polymorphisms were observed in transferrin (variants A, B1, B2, C) and vitamin D binding protein, GC (variants D, F, I, S). Great variability was observed in the protease inhibitors PI2, PI3, PI4, PI5, and PI8 and in unidentified zones in the vicinity of albumin, but no genetical or physiological interpretation for this variability is yet available. Haemopexin, alpha 1 glycoprotein, protease inhibitors PI1, PI6 and PI7 were monomorphic. PMID- 2268076 TI - Genetic polymorphism of serum vitamin D-binding protein (GC) in sheep and mouflon. AB - One-dimensional polyacrylamide gel electrophoresis (1D PAGE) followed by immunoblotting revealed genetic polymorphism of GC protein in sheep (variants F, S, V) and mouflon (variants F and S, apparently identical to F and S of sheep). The frequency of Gcs allele ranged from 0.84 to 1.0 in the 12 breeds of sheep studied. GcV allele was observed only in Tsigai breed with a frequency of 0.017. PMID- 2268077 TI - Linkage studies on erythrocyte antigen loci, the major histocompatibility complex and the haemoglobin beta gene cluster in goats. AB - Linkage studies on seven erythrocyte antigen loci, the major histocompatibility complex (MHC) and the haemoglobin beta gene cluster (HBB) were performed in 48 Norwegian goat families. Close linkage was excluded between the erythrocyte antigen B-system and the MHC, between the erythrocyte antigen N7 locus and HBB, and between the MHC and the HBB. PMID- 2268078 TI - Additional information on the linear order of the genes encoding the red blood group C-system antigens in cattle. AB - A linear model for the genes controlling the system C blood group factors was presented by Bouw et al. (1974) and confirmed by Guerin et al. (1981). The relative order of the R and W genes was not established by either of these studies. A recently observed recombination in the C system is reported here, providing evidence for the positioning of the R and W genes. PMID- 2268080 TI - HIV/AIDS: America's RNs respond to deepening crisis. PMID- 2268079 TI - Transferrin and albumin polymorphisms in buffaloes from Brazil. AB - Starch gel electrophoresis disclosed six transferrin phenotypes, explainable by three alleles (TF A, TF D, TF E), and three albumin phenotypes, determined by two alleles (ALB A, ALB B). Their prevalences suggest that the Brazilian populations have admixed river and swamp buffalo ancestry, the frequency of ALB A being much higher than those found in other regions. PMID- 2268081 TI - Nursing wins reimbursement, funding victories. PMID- 2268082 TI - ANA policies support fight against HIV. PMID- 2268083 TI - HIV and children: a growing problem. PMID- 2268084 TI - Needlesticks put RNs at risk. PMID- 2268085 TI - Caring for HIV patients raises legal issues. PMID- 2268086 TI - The challenge of HIV nursing. PMID- 2268087 TI - HIV jolts our complacency. PMID- 2268088 TI - HIV exposes cracks in health care system. As I see it. PMID- 2268089 TI - AIDS nursing--challenging, rewarding. As I see it. PMID- 2268090 TI - Behavior as the central outcome in health care. AB - A predominant justification for health psychology and behavioral medicine is that behavior or environmental conditions affect a biological process. Thus, many investigators focus attention on the effects of behavior on cell pathology and blood chemistry. This article argues that behavioral outcomes are the most important consequences in studies of health care and medicine. These outcomes include longevity, health-related quality of life, and symptomatic complaints. Traditional measures in biomedical science often have limited reliability and validity. Their validity is demonstrated only through relationships with longevity, role performance, behavioral functioning, and symptomatic experience, and these correlations are often modest. A model is proposed to guide future investigations. Biological, environmental, and psychological variables are included in the model as predictors or mediators of behavioral health outcomes. Recognizing that health outcomes are behavioral directs intervention toward whatever method produces the most health benefit at the lowest cost. PMID- 2268091 TI - Structure in language. Creating form in talk. AB - In psycholinguistics, the systematic study of language production has begun to take a place beside the study of language comprehension as a means to the end of understanding human language use. Because a major and very visible component of speaking a language is knowing how to create forms to carry messages, efforts to explain language production must confront long-standing questions about the relationship between structure and function in psychological explanation. One traditionally appealing view of that relationship in the realm of language is that sentence structures are associated with or reducible to the general forces of cognition that drive interpretation and communication. This article surveys some of the challenges to this view that emerge from the study of speech errors, and sketches the progress that has been made in developing an alternative view, renewing the argument that syntactic structures are necessary elements in an explanation of language use. PMID- 2268092 TI - Community-based care for the mentally ill: simple justice. PMID- 2268093 TI - Planning a community-based mental health system. Perspective of service recipients. PMID- 2268094 TI - Planning a community-based mental health system. Perspective of a family member. PMID- 2268095 TI - Understanding the current facts and principles of mental health system planning. PMID- 2268096 TI - A catalyst for change. The art of strategic mental health planning in Rhode Island. PMID- 2268097 TI - Survey of current clinical and research trends in clinical psychology. AB - A survey of the directors of APA accredited clinical psychology programs was conducted to explore current trends in the training of clinical psychologists. Specifically, information was obtained regarding the research areas represented at each school, the types of clinical training sites available to graduate students, and the prevalence of different clinical orientations (e.g., cognitive behavioral, systems, or psychoanalytic). Results of the survey provide a summary of the activities of faculty and students at the more than 100 fully accredited clinical psychology programs. PMID- 2268098 TI - The current spectrum of peptic ulcer disease in the older age groups. AB - Not only has there been a relative increase in the prevalence of peptic ulcer disease (PUD) among America's older age groups, but the characteristics of PUD in these patients differ significantly from those of the general population. Seventy two consecutive patients 60 years of age or older who underwent operation for PUD between 1984 and 1989 were studied. The unusual features in these patients were 1) 92 per cent required emergency operation, 2) 57 per cent with perforated PUD were female, 3) 85 per cent had duodenal pathology, 4) 28 per cent were currently taking nonsteroidal anti-inflammatory agents, and 5) over one half of all patients had serious postoperative complications. The increasing incidence and associated serious complications of PUD in the elderly population present new challenges to physicians in the diagnosis and treatment of this disease. PMID- 2268099 TI - The elusive colonic malignancy. A need for definitive preoperative localization. AB - Colonoscopy with biopsy is the standard of practice for the diagnosis of colonic malignancies. Unfortunately, the inability of endoscopy to obtain precise distance measurements from the anal verge can make localization of lesions at operation difficult. For this reason, preoperative barium enema or intraoperative colonoscopy have been advocated to further pinpoint the sites of those lesions not thought to be easily located at operation. Five patients are presented in whom malignant lesions of the colon were diagnosed and verified histologically, but were later undetectable at operation or subsequent colonoscopic examinations. Four of these patients underwent laparotomy and three received colon resections. None of these patients' tumors were identified during intraoperative colonoscopy, in the resected bowel on pathologic examination, or on follow-up colonoscopy. A fifth patient is presented who spontaneously passed a polyp containing invasive adenocarcinoma, but multiple colonoscopic examinations have failed to identify the site of the lesion. To date, none of these tumors have recurred with periods of follow-up ranging from 6 months to 2 years. These patients demonstrate a poorly documented and little understood aspect of the behavior of colonic malignancies, i.e., the ability to spontaneously regress or slough from the bowel wall. Based on these instances, localization of potentially malignant colon lesions is recommended with submucosal dye injections at initial endoscopy or with colonoscopy in the operating room immediately prior to operation. PMID- 2268100 TI - Surgery for thoracoabdominal aortic aneurysms. AB - From July 1985 to July 1989, Loma Linda University Medical Center evaluated 46 thoracoabdominal aortic aneurysms (TAAAs). Forty patients were taken to surgery- 18 (45%) were operated on an emergency basis for reasons including rupture (12 patients, 30%), dissection (5 patients, 12.5%), and severe pain (1 patient). The overall mortality for all operated patients was five (12.5%-17% for emergency surgery versus 9% for elective surgery). Nonfatal complications occurred in 40 per cent of patients (16). The overall incidence of paraplegia was 10 per cent (4/40), emergency patients 17 per cent (3/18) versus elective patients 4.5 per cent (1/22). Careful preoperative evaluation, standardization of operative technique, and good postoperative management have improved the outlook for these patients who otherwise would progress to eventual rupture and death. Because mortality and morbidity are substantially reduced in elective patients, we recommend that all patients with TAAAs be evaluated for surgery as soon as diagnosis is made. PMID- 2268101 TI - Survival after hypertonic saline resuscitation from hemorrhage. AB - There has been recent increased interest in hypertonic saline resuscitation from shock and hemorrhage. This study was performed to evaluate the survival effects of hypertonic saline resuscitation. Fifty male Sprague-Dawley rats of average weight of 325 grams were anesthetized with halothane. Animals were subjected to blood loss of 21 ml/kg over 5 minutes. Intravenous infusion was started 10 minutes after hemorrhage with either lactated Ringer's injection (42 ml/kg) or three per cent NaCl (10.64 ml/kg) chosen randomly. These doses provided equal amounts of sodium. At the end of fluid infusion, blood samples were obtained for electrolyte determination. Rats were observed 3 days for survival. Survival was significantly lower in the three per cent NaCl group compared with the lactated Ringer's group. It is probable that worsened outcome with three per cent NaCl was associated with intracellular dehydration. PMID- 2268102 TI - Sinistral (left-sided) portal hypertension. AB - Between 1953 and 1988, 21 patients with splenic vein thrombosis (SVT), 12 of whom had sinistral portal hypertension (SPH) were treated at our institution. SVT was identified at autopsy in nine patients. Twelve additional patients presented with SPH: bleeding esophageal varices, SVT and normal hepatic function. SVT was caused by pancreatic neoplasm (5), chronic pancreatitis (5), and pancreatic pseudocyst (2). SVT was diagnosed by splanchnic angiography, splenoportography, computerized tomography, and ultrasonography. Gastric varices were diagnosed by endoscopy (10) and barium swallow (2). Splenectomy was performed as primary therapy in 10 patients. Three of these 10 had en block distal pancreatectomy. Two high-risk patients had splenic artery embolization, one as a prelude to splenectomy performed 48 hours later and the other as definitive therapy. One splenectomized patient continued to bleed. No further bleeding occurred in 10 splenectomized patients in follow-up from 1 week to 14 years. Sinistral portal hypertension is a clinical syndrome of splenic vein thrombosis caused by pancreatic pathology and manifests as bleeding gastric varices in patients with a patent portal vein and normal hepatic function. Splanchnic arteriography is necessary for accurate diagnosis. Splenectomy is the effective treatment of choice. PMID- 2268103 TI - Fine needle aspiration of pancreatic fluid collections. AB - The complications of pancreatitis remain diagnostic and therapeutic challenges. Patients with simple pancreatitis, pancreatic necrosis, pseudocyst, noninfected fluid collection or abscess may all have similar clinical pictures. During the last decade computerized tomography (CT)-guided needle aspiration of peripancreatic fluid collections has been increasingly used as a diagnostic tool for pancreatic abscesses. This study reviewed the effectiveness of CT-guided needle aspiration of peripancreatic fluid collections at our institution in terms of diagnostic accuracy, correlation with eventual outcome, and safety. Charts of patients who underwent needle aspiration of de novo peripancreatic fluid collections over the past 2 years were reviewed. Thirty-five patients underwent 50 aspirations. Eleven patients (31%) had a positive aspirate culture; seven of these had a positive Gram's stain. There were no false positive Gram's stains but four false negatives. Twenty-four (69%) patients had negative aspirate Gram's stains and cultures. Patients with positive aspirate cultures were treated with antibiotics only (2), CT-guided drain placement (7), or surgical drainage (3). The mortality related to each of these therapeutic modalities was 50 per cent, 0 per cent, and 33 per cent, respectively. Of the 24 patients with negative aspirate cultures, five had no further treatment, 12 received antibiotics, and six underwent CT drain placement. All these patients survived. There was one false negative aspirate culture. This patient underwent delayed surgical drainage but expired. There were no major complications from CT-guided aspiration. CT guided aspiration appears to be a safe and reliable method of diagnosing infection in peripancreatic fluid collections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268104 TI - The intracolonic bypass tube for left colon and rectal trauma. The avoidance of a colostomy. AB - Traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy. Primary repair without colostomy is much less commonly employed. We report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube (ICBT) without concomitant colostomy. In all these patients we believe the standard treatment would have included fecal diversion. Four patients sustained blunt trauma and five sustained penetrating trauma. Healing of the colonic anastomosis occurred in all cases, and the ICBTs were passed per rectum between the tenth and nineteenth days postoperatively. On the basis of this study, we conclude that the ICBT has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy. PMID- 2268105 TI - Partial splenic embolization. An effective alternative to splenectomy for hypersplenism. AB - Splenectomy for massive splenomegaly and hypersplenism carries a significant morbidity and mortality. We have used partial splenic embolization (PSE) as an effective alternative to splenectomy. Ten PSE procedures were performed on nine patients without mortality and with minimal morbidity. The age of the patients ranged from 8 months to 32 years (mean 14 years). The causes of splenomegaly and hypersplenism included cystic fibrosis with cirrhosis (2), tyrosinemia and cirrhosis (1); thalassemia (1), hemophilia with Human Immune Deficiency Virus infection (2), chronic hepatitis with portal hypertension (1), malignant histiocytosis (1), and Wiskott-Aldrich Syndrome (1). All procedures were performed under local anesthesia with sedation. A percutaneous femoral artery approach to the splenic artery was used to deliver Ivalon sponge particles (280 800 microns) into the spleen. Splenic infarction was assessed by postembolization angiograms. All of the patients except one demonstrated improvement of hematologic parameters. In one patient, however, cytopenia improved only after a second embolization. In the total series, there was an early mean rise of 8,600/mm3 in the leukocyte count (range 2,900-14,900) and 212,000/mm3 in the platelet count (range 30,000-718,000). Follow-up ranged from 4 months to 7 years. Improvement of the blood picture has been persistent in seven of the eight patients who showed initial improvement. Transient procedural complications included fever (5), pleural effusion (2), pneumonia (1), and splenic abscess (1). One patient had paralytic ileus lasting for 10 days and one patient developed a streptococcal peritonitis 3 weeks after embolization. No patient developed pancreatitis or vascular compromise of other abdominal viscera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268106 TI - Carotid artery disease in patients with head and neck carcinoma. AB - Irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries. However, occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown. Therefore, we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979-1987. Of these 179 patients, 107 (59.8%) were dead at time of follow-up. Cause of death was unknown in 42 (40%) patients; in the remainder included: respiratory arrest--33; carcinoma-related--18; cardiac--6;pneumonia--7; and trauma--1. Average interval from treatment to death was 23.5 months. Of the 72 patients known to be alive, follow-up was obtained in 52 patients. Their average age was 64.9 years. Risk factors for atherosclerosis included: male gender--43; smoking--50; hypertension- 9; diabetes--4; coronary artery disease--12; and peripheral vascular disease--4. Seventy-five per cent of these patients received postoperative irradiation. Average follow-up was 64.5 months. Duplex scans were performed on 34 patients. Three patients had common or internal carotid stenoses greater than 75 per cent. All of these patients had received irradiation and none of them were symptomatic. Seven patients had carotid stenoses between 50 to 75 per cent; five of these had received irradiation. Of these five patients, one had a stroke 60 months postoperatively, and one had a TIA 36 months postoperatively. The remaining 58 patients (of which 48 had irradiation) had carotid stenoses less than 50 per cent and none were symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268107 TI - The pathology of nonpalpable breast cancer. AB - A principal goal of mammographic screening is the early detection of breast cancer. We reviewed records of 125 women who were referred because of nonpalpable, suspicious abnormalities on mammogram, which subsequently proved to be cancer, requiring mammographic localization biopsy and subsequent surgery for therapy. We found that 72 (57.6%) had invasive tumors, 15 (12%) showed evidence of microinvasion and 38 (30.4%) were noninvasive. A total of 115 patients had lymphadenectomy as part of their definitive surgery. Nine (12.7%) of the patients with infiltrating tumors had between one and 10 malignant nodes on histologic section. None of the patients with noninvasive or microinvasive tumors were found to have involved nodes. The mammographic abnormalities which led to biopsy in our series were: calcifications in 74 (59.2%) patients, mass lesions in 39 (31.2%), mass lesions with calcifications in 11 (8.8%), and asymmetry in one (0.8%). Of the nine patients with nodal metastases, seven (77.8%) had a mass with or without calcifications as the indication for biopsy. Increasing tumor size was found to correlate with invasive tumors on histopathologic examination and the incidence of lymph node metastases. Thirty-seven (54.4%) of the patients with infiltrating tumors had a tumor size greater than 1 cm. Further, seven (77.8%) of the nine lymph node positive patients had tumors between 1 and 3 cm in size. Of note, however, is that two (22.2%) patients with microscopic tumors had involved nodes. The 4-year actuarial survival in patients with infiltrating tumors was 85.2 per cent, while that for patients with noninvasive or microinvasive tumors was 100 per cent (median follow-up of 20 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268108 TI - One-stage repair of colovaginal fistula complicating acute diverticulitis. AB - Fourteen patients with colovaginal fistula secondary to sigmoid diverticulitis were seen between 1964 and 1988. Thirteen had undergone prior hysterectomy. Three different operative approaches were used. Three patients were treated with colostomy alone; one died and the fistula persisted in one. Five patients underwent staged procedures. One patient died of complications after the second stage of a planned three-stage procedure. Four patients underwent a two-stage procedure (fistula takedown, colectomy with colostomy and colostomy closure), all with good results. Six patients were treated with one-stage fistula takedown, colectomy and primary anastomosis, without major complication. We advocate this as the procedure of choice and emphasize the following principles of epidemiology and management: 1) colovaginal fistula complicates diverticulitis in elderly women usually following hysterectomy; this association may be a factor in etiology; 2) vaginography is useful in diagnosis; and 3) planned one-stage repair is the best surgical approach. PMID- 2268109 TI - The clinical significance of fluid collections in acute pancreatitis. AB - Computed tomography (CT) displays fluid collections in patients with acute pancreatitis as well defined intra- or extrapancreatic homogeneous areas with low attenuation numbers. We followed, prospectively, the clinical courses of 128 patients who had CT during an episode of acute pancreatitis, to determine the natural history and clinical significance of any fluid collections that developed. Fluid collections were found in 48 (37%) of the 128 patients with pancreatitis. Thirty-eight developed in the 86 (44%) patients with alcoholic pancreatitis, five in the 33 (15%) with biliary pancreatitis and five in the nine (55%) with other causes of pancreatitis (excluding chronic pancreatitis, trauma, or malignancy). On clinical follow-up of the 48 patients with fluid collections, 21 patients required operation; two died before an operation was done and 25 did not require operation. Operations were done to treat pseudocysts (14), abscess (5), and necrosis (3). One patient had an operation for a pseudocyst and an abscess. All 14 patients requiring operation for pseudocyst had collections greater than 7 cm and 13 of these patients had alcoholic pancreatitis. Of the 25 patients not requiring operation, five were lost to follow-up, and 19 of the 20 who had spontaneous resolution of their fluid collection(s) had collections less than 6 cm in diameter. The eight patients who required operative pancreatic debridement for abscess or necrosis had multiple small fluid collections. In summary, fluid collections were found in one-third of patients with acute pancreatitis and were often associated with the development of local complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268110 TI - Inguinal hernia complicating flexible sigmoidoscopy. AB - Flexible sigmoidoscopy has become part of routine preoperative workup for patients over the age of fifty who present with an inguinal hernia. A recent experience with two patients with a left inguinal hernia allowing sigmoid colon to herniate into the scrotum bring awareness of the possibility for an increased risk of perforation of the sigmoid colon during flexible sigmoidoscopy, or possible iatrogenic incarceration of the hernia. These cases are presented so this clinical entity can be recognized and the complications prevented. PMID- 2268111 TI - Left atrial to femoral arterial bypass using the biomedicus pump for operations of the thoracic aorta. AB - Left atrial to left femoral arterial bypass is an approach to operations of the thoracic aorta dating back to the late 1950s. Since that time, various modifications of the basic bypass circuit have evolved. In addition, temporary bypass shunts have also been described in a variety of positions. The goals of bypass of the thoracic aorta regardless of the technique include prevention of distal hypoperfusion, which can lead to paraplegia, limb loss, multiple organ failure, and sometimes death. Recently, there have been reports of the use of the biomedicus centrifugal pump in bypass circuits of the thoracic aorta. Our series, as well as the success of others, using this variation of a traditional bypass circuit of the thoracic aorta, establishes the biopump's capability of minimizing inherent complications in the bypass circuit. PMID- 2268112 TI - Computerized tomography as an indicator of isolated mesenteric injury. A comparison with peritoneal lavage. AB - This study evaluated 18 patients with blunt abdominal trauma who suffered isolated mesenteric injuries, diagnosed at exploratory laparotomy. Thirteen had diagnostic peritoneal lavage (PL) as their initial diagnostic study, and five had computed tomography (CT). All patients who had positive PL were explored emergently, undergoing repair of mesenteric injuries. Three of the five patients with CT as initial studies had delayed recognition of their injuries due to incorrect initial interpretation of the scan in two, and a false negative scan in one. Two of these patients developed intestinal infarction and required bowel resection. There were no complications in the PL group related to surgery; morbidity was greater in those undergoing CT. We conclude that early laparotomy and repair of significant mesenteric injuries is necessary to reduce morbidity, and that PL is a more sensitive indicator of this injury than CT. PMID- 2268113 TI - Studies of the initiation of myelination by Schwann cells. AB - The rapid morphologic changes in Schwann cells and in their relationships to axons during the transition from the premyelinating to the myelinating state have been known for more than 15 years. The sorting of axons by dividing Schwann cells, the establishment of a 1:1 relationship between a postmitotic Schwann cell, and the onset of myelin sheath formation have all been described in detail. However, the chain of molecular events and mechanisms by which these morphologic changes are regulated has not been elucidated. In this chapter we have reviewed results that strongly suggest that the adhesion molecule L1 is one of the important determinants that mediate the elongation of the Schwann cell along the axon, and the extension of Schwann processes to engulf axons. Thus, L1 functions to promote the spreading of the Schwann cell process over the surface of the axon. L1 does not appear to be exclusively involved in the adhesion of Schwann cells to axons, in the activation of Schwann cell proliferation by axons, or in the induction of synthesis of extracellular matrix proteins. The results from the anti-L1 blocking experiments further provided clues for an understanding of how the expression of GalC and MAG, which are both likely to be involved in the initiation of myelination, are regulated. These results imply that the overall regulation of expression of these early myelin components could require controls other than a single signaling mechanism derived from contact with axons. We propose that the deposition of basal lamina or one of its components could also be involved. Finally, the results from anti-GalC-blocking experiments indicated that GalC is involved in the mechanism of early growth of the myelin spiral. PMID- 2268114 TI - Dissection of the phenotype and genotype of the X-linked myelin mutants. PMID- 2268115 TI - Expression of the jimpy phenotype in relation to proteolipid protein appearance. PMID- 2268116 TI - Phylogeny of myelin proteins. PMID- 2268117 TI - Axolemmal abnormalities in myelin mutants. AB - Evidence is reviewed that the paranodal axoglial junction plays important roles in the differentiation and function of myelinated axons. In myelin-deficient axons, ion flux across the axolemma is greater than that in myelinated fibers because a larger proportion of the axolemma is active during continuous, as opposed to saltatory, conduction. In addition, older myelin-deficient rats that have developed spontaneous seizures display small foci of node-like E-face particle accumulations in CNS axons as well as more diffuse regions of increased particle density and number. Assuming that the E-face particles represent sodium channels, such regions could underlie high sodium current density during activity, low threshold for excitation, and increased extracellular potassium accumulation. Depending on the degree of spontaneous channel opening, they could also represent sites of spontaneous generation of activity. The appearance of seizures and their gradual increase in frequency and severity could represent an increase in the number of such regions. In addition, diminution in the dimensions of the extracellular space during maturation would result in increased extracellular resistance, which, together with increasing axonal diameter, would tend to increase the likelihood of ephaptic interaction among neighboring axons as well as the likelihood of extracellular potassium rises to levels that could cause spontaneous activity. PMID- 2268118 TI - Posttranscriptional events in the expression of myelin protein genes. AB - A number of posttranscriptional events may be involved in regulating the expression of the myelin protein genes. One such event in the expression of the myelin basic protein (MBP) gene is the translocation of MBP mRNAs from oligodendrocyte cell bodies to their processes. This translocation can be observed in vivo and in primary mixed glial cell cultures. In jimpy brains the translocation of MBP mRNA appears to be disrupted, so that most of the mRNA remains associated with cell bodies. This apparent failure of translocation may account for the lack of incorporation of newly synthesized MBP into jimpy myelin. In quaking myelin, where MBP assembly is also defective, translocation appears to be normal, suggesting that incorporation of MBP into the membrane also is regulated posttranslationally. We have identified a number of the structural features of MBP mRNAs that influence the efficiencies with which they are translated and may be involved in regulating the levels of individual MBP produced. We also found that glucocorticoids stimulate the translation of MBP and PLP mRNAs and inhibit the translation of CNP mRNA in cell-free systems. Our results suggest that this pattern of translational regulation may be physiologically meaningful, especially during maturation of myelin. The mechanism by which the steroids modulate translation of these messages appears to be novel. Analysis of the effect of steroids on cRNAs produced from engineered MBP cDNA constructs has permitted the identification of a nine nucleotide element involved in this steroid modulation within the 5' untranslated region of the MBP mRNA. PMID- 2268119 TI - Myelin pathology in the twitcher mouse. PMID- 2268120 TI - What have we learned about the jimpy phenotype expression by intracerebral transplantations? PMID- 2268121 TI - Metabolic organization of the myelinating Schwann cell. PMID- 2268122 TI - Developmental and hormonal regulation of gene expression in oligodendrocytes. PMID- 2268123 TI - Glycolipids and transmembrane signaling in oligodendroglia. PMID- 2268124 TI - [Role of modern imaging (CT-MRI) in the preoperative evaluation of bronchial cancers. Results in 202 cases]. AB - The authors present the results of a comparative prospective study of the staging 202 bronchogenic carcinomas (T and N) before surgery. The results of CT (202 cases) and MRI (64 cases) were compared with surgical evaluation and pathologic findings. CT and MRI were part of the decisive criteria for therapeutic-surgery choice and were interpreted before surgery. The results showed poor sensitivity for the T and N but better specificity. MRI is superior to CT with the 3 dimensional demonstration and T1 T2 weighted sequences, but its utility remains limited. The authors give their preferred indications for MRI investigation after CT staging. Staging by CT (and MRI) is of great value to avoid impossible thoracotomy and to confirm the findings of mediastinoscopy (suspected N2 and even more N3). PMID- 2268125 TI - [Radiologic aspect of benign pleural fibrous mesothelioma. Reports of 4 cases]. AB - Solitary fibrous tumor or pleural fibroma is a rare tumor. It grows slowly and has a good prognosis after surgical resection. Pleural features, staging and even the fibrous nature are analysed by radiological findings. Ultrasonic diagnosis, CT-Scan and MR Imaging are very useful but non specific: the differential diagnosis between benign and malignant tissue is still based on histological study of the whole surgical specimen. Review of the literature. PMID- 2268126 TI - [Carcinoid tumor metastases visualized by I-MIBG. Report of 5 cases]. PMID- 2268127 TI - [Uterine cervix cancers: staging by magnetic resonance imaging]. AB - The accuracy of Magnetic Resonance Imaging in cervical carcinoma staging for clinical stages superior to IB was studied retrospectively in 27 patients. The MRI results were then correlated with operative findings in 12 cases and with examination carried out under general anesthesia in 15 cases for myometrial, bladder, rectal, parametrial, parietal and vaginal extension. The accuracy of MRI was 81.5% for bladder, 92.5% for rectal, 87% for parametrial and 73% for vaginal extension. The accuracy of staging by MRI was 59%. The contribution of MRI in pre operative studies for cervical carcinomas has not been properly defined until now. Nevertheless it is a particularly valuable technique due to its non invasive nature. PMID- 2268128 TI - [Digitalized angiography in the study of critical ischemia of the lower limbs]. AB - Twenty three patients suffering from severe chronic ischemia of the lower limbs were explored by conventional and digital angiography. A comparative study of these 2 angiographic techniques was carried out to appreciate the pre-operative distal vascular tree and the surgical indications. In all cases, digital angiography was never found to be less informative than conventional angiography. In 14 cases, the surgical approach was changed as a result of digital angiography in 4 cases the method of revascularization and in 10 cases the surgical indication itself (distal bypass instead of amputation). The authors consider digital angiography to be essential in this surgical indication. PMID- 2268129 TI - [Methanol poisoning. Report of 2 cases studied with x-ray computed tomography and magnetic resonance imaging]. AB - The authors report 2 cases of deliberate methanol intoxication explored by Computed Tomography and MR Imaging. These two methods gave similar results showing bilateral areas of putaminal necrosis. This characteristic finding is of great diagnostic value in these clinically-oriented cases. MRI gives better anatomical details and may reveal small haemorrhagic lesions. PMID- 2268130 TI - [Hepatic angiosarcoma. CT and MRI aspects. A case report and review of the literature]. AB - The authors report a case of hepatic angiosarcoma revealed by massive haemoperitoneum. They analyse the CT and MRI features of this rare tumour and recall the difficult diagnostic problems raised by cavernous angiomas. The new MRI diagnostic criteria must be recognized, but do not constitute formal proof of the diagnosis. PMID- 2268131 TI - [Isolated dissection of the celiac trunk and its branches. X-ray computed tomography and angiography findings. A case report]. AB - A case of primary dissection of the celiac trunk in a young hypertensive patient is presented. The diagnosis, suspected by ultrasonography, was confirmed by angiography and CT which also allowed a study of the visceral complications. Appropriate surgical treatment was successfully carried out. PMID- 2268132 TI - [Esophageal mucoceles complicating double exclusion of the esophagus after ingestion of caustics]. AB - A mucocele is rarely observed after esophageal exclusion for corrosive burns. It may represent a contra-indication to esophageal conservation in case of a total gastric resection for necrosis and perforation of the stomach. To evaluate this risk, 15 patients, operated between January 1970 and december 1988, were reviewed: they underwent total gastric resection with esophageal exclusion, followed by a secondary colon transplant between the cervical esophagus and the duodenum. A plain chest film was performed for 13 patients and a CT scan for 11 patients. Mean follow-up was 5.7 years (2 months - 17 years). Four patients died, one of them after resection of a compressive esophageal mucocele. Six mucoceles were detected on 13 chest films and 7 were described on 11 CT scans. On the whole, 8 mucoceles were diagnosed on 15 patients; one of them was complicated by tracheal compression. The formation of a secondary esophageal mucocele is a late sign of incomplete destruction of the esophageal wall. It is a frequent complication of esophageal exclusion performed after total gastrectomy for corrosive burns of the stomach. It must be detected on a chest film which shows the largest dilatations or on a CT scan, which is a better investigation. When the diameter of the mucocele is equal of superior to 50 mm, it can be compressive and must be treated by resection of internal diversion. PMID- 2268133 TI - [Ultrasound-guided puncture. Modern treatment of liver abscess]. AB - The treatment of liver abscesses has benefitted from progress in imaging, particularly ultrasonography which allows simple and reliable aspiration and drainage. A series of 32 cases is reported, consisting of 29 pyogenic abscesses and 3 amoebic abscesses. Eighty-one per cent of patients were cured by aspiration and/or drainage, while 19% of patients had to be operated. The mean hospital stay was 11 days. Failures of ultrasound-guided aspiration are essentially due to multifocal abscesses caused by multiple organisms. PMID- 2268134 TI - [Textile foreign bodies left in the abdomen]. AB - The authors relate eleven cases of forgotten foreign bodies (5 swabs and 6 laparotomy pads) in the abdomen after laparotomies for biliary and digestive (5 cases), gynaecologic (3 cases), or abdominal-wall (3 cases) diseases. Ten patients recovered after surgical extraction of foreign bodies (morbidity: 2 cases) and one patient died before reoperation. This study emphasizes the severity of this complication which can and should be prevented. PMID- 2268135 TI - [Synovial chondromatosis of the hip]. AB - The authors report a case of synovial chondromatosis of the hip in physically active male adult operated on three years ago and apparently cured. Review of the literature shows that the diagnosis, essentially based on X-ray examination, bone scan and arthrography, needs to be confirmed by histological examination. Treatment must be surgical and must be carried out as soon as possible to prevent arthrosis. Surgery should include thorough excision of the synovial membrane and a curettage of the acetabular fossa to avoid recurrence. Under these conditions, prognosis appears to be excellent. PMID- 2268136 TI - Hunger ratings are not a valid proxy measure of reported food intake in humans. AB - Hunger ratings have been used as proxy measures of food intake although their validity has not been established. To address this issue, 12 female and 12 male adults of normal weight recorded food intake and hunger ratings every waking hour for 7 consecutive days. Discrepancies were noted in the correlation between hunger ratings and computed energy intake on weekdays vs. weekends, and no significant correlations were observed for individual subjects. Eating often occurred when hunger ratings were low or had not increased, and few individuals displayed a significant correlation between hunger ratings and number of eating occurrences. It was concluded that hunger ratings are not a valid index of energy intake computed from food records or number of eating occurrences. PMID- 2268137 TI - Foods with different satiating effects in humans. AB - The aim of this study was to identify particular properties of foods that can affect satiety. Two levels (50 and 200 kcal) of three preloads (tomato soup, melon, cheese on crackers) were given just before two different second courses (macaroni and beef casserole, grilled cheese sandwiches), allowing us to examine the effects of caloric level, energy density, and sensory-specific satiety on food intake in normal weight, non-dieting males. Eating time and initial palatability ratings were held constant. Soup was found to reduce second course intake significantly more than the other preloads. This reduction could be partially accounted for by the low energy density of tomato soup; however, soup reduced intake more than the melon preload, which was matched for energy density. Sensory-specific satiety did not explain the satiating efficiency of the soup. Thus, during a meal, tomato soup is more satiating than the melon and cheese on crackers. Further studies are required to determine why these foods have different effects and to determine whether soup consumption can be beneficial in weight reduction programs. PMID- 2268138 TI - Use and perceived attributes of cruciferous vegetables in terms of genetically mediated taste sensitivity. AB - Bitter tasting compounds in cruciferous vegetables resemble chemically the compound phenylthiocarbamide (PTC). As sensitivity to PTC is genetically mediated, it was hypothesized that this characteristic would be linked to greater sensitivity of the bitter tasting components in cruciferous vegetables, and that PTC sensitivity would be reflected in less favourable sensory perceptions and lower use of the vegetables. PTC status was determined for healthy, racially and culturally similar women, alike in foodways and aged 18-46 years. The frequency of use and perceptions of sensory, post-ingestional and social attributes of 11 cruciferous and two non-cruciferous vegetables in both raw and cooked forms were compared between the PTC tasters and non-tasters. Minimal effects of PTC status on these factors were observed. Only two vegetables showed significant differences in use--PTC non-tasters used cooked turnip and raw watercress significantly more than did PTC tasters. Perceived bitter taste and aroma did not offer an explanation for the findings. Similarly, familiarity, early exposure, and tolerance did not account for any group differences. PTC status, especially in terms of non-tasting propensity, may have some sensory-specific effects which will impact on the use of cruciferous vegetables by young and mature women, but environmental factors may offset this effect and must be considered in studies of food behaviour. PMID- 2268139 TI - Effects of caloric manipulations on food intake in baboons. AB - Food intake of seven adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-h experimental sessions. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e. a meal, became available under the second "consumption component," during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. The effects of caloric preloads on food intake were determined by giving each baboon a meal of preferred foods 45-60 min prior to the start of the daily session. Caloric preloads decreased food intake during the first 8 h of the session, but had no effect on intake during the entire session. The effects of acute deprivation on food intake were determined by terminating sessions after a baboon had consumed 20-80% of baseline intake, and by starting a session 4-12 h late. Deprivation did not increase subsequent food intake. The effects of the availability of an alternative source of calories on total daily intake were determined by providing access to a dextrose solution. Baboons decreased intake of solid food in accordance with the caloric intake from the dextrose solutions by decreasing the number of meals. Finally, the effects of providing a diet of higher caloric density on food intake were determined. Two of the four baboons tested in this procedure maintained baseline levels of daily caloric intake, while the other two baboons increased daily caloric intake. In summary, free-feeding baboons were relatively insensitive to acute changes in feeding conditions, but were sensitive to long-term changes in the caloric content of available foods. PMID- 2268140 TI - Does emotional eating interfere with success in attempts at weight control? AB - Questionnaire responses from a convenience sample were used to test for hypothesized relationships between changes over time in individuals' reported frequency of emotional eating and estimates of their success in attempts to reduce body weight over periods of at least 1 year. Respondents were 187 English adults, whose distribution of estimated Body Mass Indices (BMI) approximately that of the general population. Initial BMI was significantly (p less than 0.001) positively associated with reported frequency of emotional eating. Moreover, respondents indicating initially relatively high levels of emotional eating who reported a reduction in that level were found to lose significantly (p less than 0.01) more reported weight and to be significantly (p less than 0.05) more successful at approaching target weight over the period of the study than respondents who continued to report high levels of emotional eating. Similarly, respondents who reported an increase from initially relatively low levels of emotional eating, while not losing significantly less reported weight, were significantly (p less than 0.05) less successful at approaching target weight than those respondents who continued to report low levels of emotional eating. PMID- 2268141 TI - Insulin stimulation of water intake in humans. AB - Drinking response to the intravenous administration of insulin (0.1 U/kg) was studied in 15 volunteers (eight males and seven females). Water intake was significantly higher after insulin than after saline administration during the 90 min period studied. Plasma glucose decreased significantly in individuals receiving insulin and the time of the maximum decrease (30 min) was concurrent with the beginning of water intake. Haematocrit values in the insulin-treated group were also significantly higher at that time. Plasma renin activity (PRA) after insulin administration was higher than under basal conditions or after saline injection. On the other hand, psychological responses indicated that insulin probably elicits thirst prior to the hunger which appears with hypoglycaemia. A possible role of endogenous insulin in meal-related thirst is hypothesized. PMID- 2268142 TI - Social facilitation of the spontaneous meal size of humans occurs regardless of time, place, alcohol or snacks. AB - The amount eaten by humans in spontaneously ingested meals is positively correlated with the number of other people present. This could be due to a social facilitation or may be produced as an artifact of a covariation produced by a third factor. Possible covariations produced by time and location of eating, alcohol intake, and snack/meal ingestion were investigated by paying 78 adult humans to maintain 7-day diaries of everything they ingested, when and where they ingested it, and the number of other people present. The results demonstrate that, although the covariances exist, they could not account for the social correlation. Strong, positive and significant correlations between meal size and the number of other people present were found separately for meals eaten during the breakfast period, the lunch period and the dinner period, eaten in restaurants, at home and elsewhere, eaten accompanied by alcohol intake or without alcohol, and for only snacks or only meals. The results suggest that the correlation results from a true social facilitation of eating and that this facilitation is an important determinant of eating regardless of whether alcohol is ingested with the meal, a snack or a meal is eaten and regardless of when or where it is eaten. PMID- 2268143 TI - Triacylglycerol lipase from rape (Brassica napus L.) suitable for biotechnological purposes. AB - Triacylglycerol lipase (EC 3.1.1.3) from rape (Brassica napus L. cv Ceres) is quite easily prepared from the 100,000 x g supernatant of cotyledon homogenates. The lipase is present in a high-molecular-mass fraction (greater than 1.5 x 10(6) dalton by gel filtration), but it can be rapidly extracted from the 100,000 x g supernatant by precipitation with polyethyleneglycol 8000 (4%, w/v) and MgCl2 (40 mM) giving about a 10-fold purification. After delipidation, the lipase has an Mr of about 300,000. It hydrolyzes triacylglycerols to fatty acids and glycerol, although the fatty acids from the sn-1 or -3 positions are hydrolyzed first to yield 1,2(2,3)-diacylglycerols. Lipase immobilized onto Celite by precipitation with acetone at -20 degrees C catalyzes the esterification of oleic acid with butanol dissolved in hexane. PMID- 2268144 TI - Protein engineering and site-directed mutagenesis. Patents and literature. PMID- 2268145 TI - Algal biotechnology. AB - The review gives a general outline of macro- and microalgal biotechnology. The main methods by which algae are cultivated and harvested are described. The first section deals with the environmental factors affecting mass culture and the principles governing the design and operation of mass cultivation systems. The second section gives the main current and potential uses of algae: in wastewater treatment, a source of food and feed, an energy source, and in the production of common and fine chemicals, such as polysaccharides, lipids, glycerol, pigments, and enzymes. Pharmaceutical uses of algae are described, and their potential as a source of novel biologically-active compounds is discussed. Future developments and the great potential of algae are considered. PMID- 2268146 TI - Transformation of carbon tetrachloride by Pseudomonas sp. strain KC under denitrification conditions. AB - A denitrifying Pseudomonas sp. (strain KC) capable of transforming carbon tetrachloride (CT) was isolated from groundwater aquifer solids. Major products of the transformation of 14C-labeled CT by Pseudomonas strain KC under denitrification conditions were 14CO2 and an unidentified water-soluble fraction. Little or no chloroform was produced. Addition of dissolved trace metals, notably, ferrous iron and cobalt, to the growth medium appeared to enhance growth of Pseudomonas strain KC while inhibiting transformation of CT. It is hypothesized that transformation of CT by this organism is associated with the mechanism of trace-metal scavenging. PMID- 2268147 TI - Reductive dehalogenation of carbon tetrachloride by Escherichia coli K-12. AB - The formation of radicals from carbon tetrachloride (CT) is often invoked to explain the product distribution resulting from its transformation. Radicals formed by reduction of CT presumably react with constituents of the surrounding milieu to give the observed product distribution. The patterns of transformation observed in this work were consistent with such a hypothesis. In cultures of Escherichia coli K-12, the pathways and rates of CT transformation were dependent on the electron acceptor condition of the media. Use of oxygen and nitrate as electron acceptors generally prevented CT metabolism. At low oxygen levels (approximately 1%), however, transformation of [14C]CT to 14CO2 and attachment to cell material did occur, in accord with reports of CT fate in mammalian cell cultures. Under fumarate-respiring conditions, [14C]CT was recovered as 14CO2, chloroform, and a nonvolatile fraction. In contrast, fermenting conditions resulted in more chloroform, more cell-bound 14C, and almost no 14CO2. Rates of transformation of CT were faster under fermenting conditions than under fumarate respiring conditions. Transformation rates also decreased over time, suggesting the gradual exhaustion of transformation activity. This loss was modeled with a simple exponential decay term. PMID- 2268148 TI - Sensitive enzyme-amplified electrical immunoassay for protein A-bearing Staphylococcus aureus in foods. AB - An amperometric electrochemical immunoassay specific for protein A-bearing Staphylococcus aureus was developed. The method was based on a sandwich immunosorbent assay and incorporated an enzyme amplification step, using a NAD specific redox cycle generating NADH (C. H. Stanley, A. Johannsson, and C. H. Self, J. Immunol. Methods 83:89-95, 1985). Reduction of the mediator, ferricyanide, was dependent on the initial concentration of antigen. The final potential was measured by using a Pt disk electrode polarized at +0.8 V to the Ag/AgCl reference electrode. The assay was rapid (4 h) and generated protein A- and cell (S. aureus)-dependent signals. The system was highly sensitive and could detect 10 pg of protein A ml-1 and less than 100 CFU of S. aureus ml-1. Similar sensitivities were observed with S. aureus cultures inoculated into beef and milk, but the sensitivity was reduced slightly (ca. 10(3) g-1) with samples of Cheddar cheese. PMID- 2268149 TI - Low-affinity, high-capacity system of glucose transport in the ruminal bacterium Streptococcus bovis: evidence for a mechanism of facilitated diffusion. AB - The glucose phosphotransferase system (PTS) of Streptococcus bovis could not account for the glucose consumption of exponential cultures, and the kinetics of glucose transport were biphasic. A PTS-deficient mutant lost the high-affinity, low-capacity system but retained its ability to take up glucose at high substrate concentrations. The low-affinity, high-capacity system did not require a proton motive force or ATP and could not be driven by an artificial membrane potential in the presence or absence of sodium. Since low-affinity transport was directly proportional to the external substrate concentration and exhibited counterflow kinetics, it appeared that a facilitated-diffusion mechanism was responsible for glucose transport at high substrate concentrations. PMID- 2268150 TI - Localization of inulinase and invertase in Kluyveromyces species. AB - In vivo hydrolysis of inulin and sucrose was examined in selected yeasts of the genus Kluyveromyces. Cells, grown in sucrose-limited chemostat cultures, were subjected to treatments for the removal of inulinase, the enzyme responsible for the hydrolysis of both inulin and sucrose. The effects of these treatments were studied by measurement of inulin-dependent and sucrose-dependent oxygen consumption by cell suspensions. In Kluyveromyces marxianus var. marxianus, inulinase was partially secreted into the culture fluid. Removal of culture fluid inulinase by washing had no effect on sucrose-dependent oxygen consumption by this yeast. However, this treatment drastically reduced inulin-dependent oxygen consumption. Treatment of washed cells with sulfhydryls removed part of the cell wall-retained inulinase and reduced inulin-dependent oxygen consumption by another 80%. Sucrose-dependent oxygen consumption was less affected, decreasing by 40%. Cell suspensions of K. marxianus var. drosophilarum, K. marxianus var. vanudenii, and Saccharomyces kluyveri rapidly utilized sucrose but not inulin. This is in accordance with the classification of these yeasts as inulin negative. Supernatants of cultures grown at pH 5.5 did not catalyze the hydrolysis of inulin and sucrose. This suggested that these yeasts contained a strictly cell bound invertase, an enzyme not capable of inulin hydrolysis. However, upon washing, cells became able to utilize inulin. The inulin-dependent oxygen consumption further increased after treatment of the cells with sulfhydryls. These treatments did not affect the sucrose-dependent oxygen consumption of the cells. Apparently, these treatments removed a permeability barrier for inulin that does not exist for sucrose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268151 TI - Luminescence-based nonextractive technique for in situ detection of Escherichia coli in soil. AB - Measurement of light output by luminometry was used to estimate quantitatively the cell concentrations of luminescent strains of Escherichia coli in liquid culture and inoculated into soil. Strains were constructed in which luciferase production was autoinducible or constitutive. In the former, light output per cell varied considerably during growth but was constant in constitutive strains. In liquid culture, the lower detection limit was in the order of 10(2) cells ml 1. Sensitivity was reduced by approximately 1 order of magnitude for cells inoculated into soil, when 2 x 10(2) to 6 x 10(3) cells g of soil-1 could be detected. Light output measurements were obtained within 5 min of sampling, and luminometry therefore potentially offers a rapid and sensitive detection technique for genetically engineered microorganisms. PMID- 2268152 TI - Cloning of a gene from Pseudomonas sp. strain PG2982 conferring increased glyphosate resistance. AB - A plasmid carrying a 2.4-kilobase-pair fragment of DNA from Pseudomonas sp. strain PG2982 has been isolated which was able to increase the glyphosate resistance of Escherichia coli cells. The increase in resistance was dependent on the presence of a plasmid-encoded protein with a molecular weight of approximately 33,000, the product of a translational fusion between a gene on the vector, pACYC184, and the insert DNA. An overlapping region of the PG2982 chromosome carrying the entire gene (designated igrA) was cloned, and a plasmid (pPG18) carrying the gene was also able to increase glyphosate resistance in E. coli. A protein with a molecular weight of approximately 40,000 was encoded by the PG2982 DNA contained in pPG18. This plasmid was not able to complement a mutation in the gene for 5-enolpyruvylshikimate-3-phosphate synthase (aroA) in E. coli, and modification of glyphosate by E. coli cells containing the plasmid could not be demonstrated. The nucleotide sequence of the PG2982 DNA contained an open reading frame able to encode a protein with a calculated molecular weight of 39,396. PMID- 2268153 TI - Novel cloning vectors for Bacillus thuringiensis. AB - Seven replication origins from resident plasmids of Bacillus thuringienis subsp. kurstaki HD263 and HD73 were cloned in Escherichia coli. Three of these replication origins, originating from plasmids of 43, 44, and 60 MDa, were used to construct a set of compatible shuttle vectors that exhibit structural and segregational stability in the Cry- strain B. thuringiensis HD73-26. These shuttle vectors, pEG597, pEG853, and pEG854, were designed with rare restriction sites that permit various adaptations, including the construction of small recombinant plasmids lacking antibiotic resistance genes. The cryIA(c) and cryIIA insecticidal crystal protein genes were inserted into these vectors to demonstrate crystal protein production in B. thuringiensis. Introduction of a cloned cryIA(c) gene from strain HD263 into a B. thuringiensis subsp. aizawai strain exhibiting good insecticidal activity against Spodoptera exigua resulted in a recombinant strain with an improved spectrum of insecticidal activity. Shuttle vectors of this sort should be valuable in future genetic studies of B. thuringiensis as well as in the development of B. thuringiensis strains for use as microbial pesticides. PMID- 2268154 TI - Protease-mediated degradation of lignin peroxidase in liquid cultures of Phanerochaete chrysosporium. AB - The decline of lignin peroxidase (LiP) activity observed after day 6 in cultures of Phanerochaete chrysosporium was found to be correlated with the appearance of idiophasic extracellular protease activity. Daily addition of glucose started on day 6 resulted in low protease levels and in turn in stable LiP levels. Addition of cycloheximide to day 6 cultures resulted in virtually no change of LiP activity and extracellular protein and negligible levels of protease activity, indicating that this protease is synthesized de novo. LiP activity was found to be stable upon removal of the fungal pellets on day 6 and incubation of the extracellular fluid alone. An almost complete disappearance of LiP activity and LiP proteins and high levels of protease activity were observed upon incubation of 6-day extracellular fluid in the presence of fungal pellets. Moreover, incubation of crude or purified LiP isoenzymes with protease-rich extracellular fluid of day 11 or 11-day cell extracts resulted in a marked loss of activity. In contrast, incubation of crude LiP with boiled and clarified extracellular fluid of day 11 cultures resulted in virtually no loss of activity. These results indicate that protease-mediated degradation of LiP proteins is a major cause for the decay of LiP activity during late secondary metabolism in cultures of P. chrysosporium. PMID- 2268155 TI - Natural plasmid transformation in a high-frequency-of-transformation marine Vibrio strain. AB - The estuarine bacterium Vibrio strain DI-9 has been shown to be naturally transformable with both broad host range plasmid multimers and homologous chromosomal DNA at average frequencies of 3.5 X 10(-9) and 3.4 X 10(-7) transformants per recipient, respectively. Growth of plasmid transformants in nonselective medium resulted in cured strains that transformed 6 to 42, 857 times more frequently than the parental strain, depending on the type of transforming DNA. These high-frequency-of-transformation (HfT) strains were transformed at frequencies ranging from 1.1 X 10(-8) to 1.3 X 10(-4) transformants per recipient with plasmid DNA and at an average frequency of 8.3 X 10(-5) transformants per recipient with homologous chromosomal DNA. The highest transformation frequencies were observed by using multimers of an R1162 derivative carrying the transposon Tn5 (pQSR50). Probing of total DNA preparations from one of the cured strains demonstrated that no plasmid DNA remained in the cured strains which may have provided homology to the transforming DNA. All transformants and cured strains could be differentiated from the parental strains by colony morphology. DNA binding studies indicated that late-log-phase HfT strains bound [3H]bacteriophage lambda DNA 2.1 times more rapidly than the parental strain. These results suggest that the original plasmid transformation event of strain DI-9 was the result of uptake and expression of plasmid DNA by a competent mutant (HfT strain). Additionally, it was found that a strain of Vibrio parahaemolyticus, USFS 3420, could be naturally transformed with plasmid DNA. Natural plasmid transformation by high-transforming mutants may be a means of plasmid acquisition by natural aquatic bacterial populations. PMID- 2268156 TI - Survival of bacteria during aerosolization. AB - One form of commercial application of microorganisms, including genetically engineered microorganisms is as an aerosol. To study the effect of aerosol induced stress on bacterial survival, nonrecombinant spontaneous antibiotic resistant mutants of four organisms, Enterobacter cloacae, Erwinia herbicola, Klebsiella planticola, and Pseudomonas syringae, were sprayed in separate experiments in a greenhouse. Samples were collected over a distance of 15 m from the spray site for enumeration. Spores of Bacillus subtilis were used as tracers to estimate the effects of dilution on changes in population over distance. Viable counts of P. syringae, Enterobacter cloacae, and K. planticola decreased significantly over a distance of 15 m. Erwinia herbicola showed no significant decline in counts over the same distance. The degree of survival of P. syringae during aerosolization was dependent on ambient environmental conditions (i.e., temperature, relative humidity), droplet size of the aerosol, and prior preparative conditions. Survival was greatest at high relative humidities (70 to 80%) and low temperatures (12 degrees C). Survival was reduced when small droplet sizes were used. The process of washing the cells prior to aerosolization also caused a reduction in their survival. Results from these experiments will be useful in developing sound methodologies to optimize enumeration and for predicting the downwind dispersal of airborne microorganisms, including genetically engineered microorganisms. PMID- 2268157 TI - Effect of aerosolization on subsequent bacterial survival. AB - To determine whether aerosolization could impair bacterial survival, Pseudomonas syringae and Erwinia herbicola were aerosolized in a greenhouse, the aerosol was sampled at various distances from the site of release by using all-glass impingers, and bacterial survival was followed in the impingers for 6 h. Bacterial survival subsequent to aerosolization of P. syringae and E. herbicola was not impaired 1 m from the site of release. P. syringae aerosolized at 3 to 15 m from the site of release at a temperature of 12 degrees C and a relative humidity of 80% survived 35- to 65-fold better than P. syringae released at 27 degrees C and a relative humidity of 40%. No difference was observed in the survival of P. syringae and E. herbicola following aerosolization at the same temperature and relative humidity. Bacteria sprayed directly onto bean and oat plants established stable populations at comparable numbers on both plants over an 8-day period following inoculation. Bacteria that inoculated adjacent plants by drifting downwind up to 5 m were detectable at an initial population of 10(2) CFU/g on oats and 10(5) CFU/g on beans 2 h after the spray. However, bacterial populations on both plants were undetectable within 48 h. PMID- 2268158 TI - Regulation of protease production in Clostridium sporogenes. AB - The physiological and nutritional factors that regulate protease synthesis in Clostridium sporogenes C25 were studied in batch and continuous cultures. Formation of extracellular proteases occurred at the end of active growth and during the stationary phase in batch cultures. Protease production was inversely related to growth rate in glucose-excess and glucose-limited chemostats over the range D = 0.05 to 0.70 h-1. In pulse experiments, glucose, ammonia, phosphate, and some amino acids (tryptophan, proline, tyrosine, and isoleucine) strongly repressed protease synthesis. This repression was not relieved by addition of 4 mM cyclic AMP, cyclic GMP, or dibutyryl cyclic AMP. Protease formation was markedly inhibited by 4 mM ATP and ADP, but GTP and GDP had little effect on the process. It is concluded that protease production by C. sporogenes is strongly influenced by the amount of energy available to the cells, with the highest levels of protease synthesis occurring under energy-limiting conditions. PMID- 2268159 TI - Purification of acetoacetate decarboxylase from Clostridium acetobutylicum ATCC 824 and cloning of the acetoacetate decarboxylase gene in Escherichia coli. AB - In Clostridium acetobutylicum ATCC 824, acetoacetate decarboxylase (EC 4.1.1.4) is essential for solvent production, catalyzing the decarboxylation of acetoacetate to acetone. We report here the purification of the enzyme from C. acetobutylicum ATCC 824 and the cloning and expression of the gene encoding the acetoacetate decarboxylase enzyme in Escherichia coli. A bacteriophage lambda EMBL3 library of C. acetobutylicum DNA was screened by plaque hybridization, using oligodeoxynucleotide probes derived from the N-terminal amino acid sequence obtained from the purified protein. Phage DNA from positive plaques was analyzed by Southern hybridization. Restriction mapping and subsequent subcloning of DNA fragments hybridizing to the probes localized the gene within an approximately 2.1 kb EcoRI/Bg/II fragment. A polypeptide with a molecular weight of approximately 28,000 corresponding to that of the purified acetoacetate decarboxylase was observed in both Western blots (immunoblots) and maxicell analysis of whole-cell extracts of E. coli harboring the clostridial gene. Although the expression of the gene is tightly regulated in C. acetobutylicum, it was well expressed in E. coli, although from a promoter sequence of clostridial origin. PMID- 2268160 TI - Selection of Streptomyces ambofaciens mutants that produce large quantities of spiramycin and determination of optimal conditions for spiramycin production. AB - The aim of this work was to develop a strategy to isolate a morphologically stable mutant of Streptomyces ambofaciens ATCC 15154 which produced high titers of spiramycin. The rationale was to grow a nitrosoguanidine-mutated population for many generations under nonselective conditions followed by two cycles of protoplast formation and regeneration. A total of 2,400 surviving colonies were then screened for spiramycin production and subsequently checked for stability. From this experiment, strain 6-37 was isolated that produced 181 mg of spiramycin per liter and only one morphological type. The parent strain (ATCC 15154) produced 107 mg of spiramycin per liter and four morphological types. Strain 6-37 was then mutated with nitrosoguanidine, and 14,000 colonies were screened for spiramycin production. From this experiment, five strains were isolated that produced titers ranging from 187 to 373 mg of spiramycin per liter. Subsequent media and time studies with these strains resulted in a fermentation that produced 1,728 mg of spiramycin per liter. PMID- 2268161 TI - Increased sensitivity of the rapid hydrophobic grid membrane filter enzyme labeled antibody procedure for Escherichia coli O157 detection in foods and bovine feces. AB - Several strains of Escherichia coli O157:H7 artificially inoculated into vegetables and dairy products were recovered on hydrophobic grid membrane filters and enumerated by an enzyme-labeled antibody assay. The mean of the recoveries from 12 fresh vegetables was 108.8%, whereas that from 10 dairy products was 93.2%. Modified tryptic soy broth at 43 degrees C with shaking at 100 rpm provided optimum recovery of the organism from meat, with a sensitivity of less than or equal to 1 CFU/g, which is 10 times more sensitive than direct plating. The method performed equally well with vegetable and dairy products. Tryptic soy broth, however, under the same conditions gave the best results for fecal samples. Of 22 asymptomatic dairy cattle, reported as having positive Brucella titers when assayed with polyclonal antibodies, eight were found to contain E. coli O157 in their feces as demonstrated by the enzyme-labeled antibody assay by using monoclonal antibodies. This finding may explain some of the false-positive Brucella tests. PMID- 2268162 TI - Improved membrane filtration method incorporating catalase and sodium pyruvate for detection of chlorine-stressed coliform bacteria. AB - In vitro pure culture studies were conducted on three different strains of Escherichia coli (K-12, EPA 00244, and SWEI) to determine the effect of chlorination on catalase activity. In each case, stationary-phase cells exhibited significant (P less than 0.001) reductions in enzyme activity following exposure to chlorine. Mean differences in activity between control and chlorine-stressed cells ranged from 8.8 to 20.3 U/mg of protein for E. coli SWEI and EPA 00244, respectively. Following initial enzyme studies, resuscitation experiments utilizing the membrane filtration technique were conducted on chlorinated sewage effluent. Five different amendments, including catalase (1,000 U per plate), heat inactivated catalase (1,000-U per plate), sodium pyruvate (0.05%), a catalase sodium pyruvate combination (1,500 U/0.01%), and acetic acid (0.05%), were tested for the ability to enhance detection of chlorine-stressed cells on M-fecal coliform (M-FC), mT7, M-Endo, and tryptone-glucose-yeast extract (TGY) media. Significant (P less than 0.001) increases in recovery of fecal coliforms on M-FC, total coliforms on mT7 and M-Endo, and total heterotrophs on TGY were obtained on plates containing catalase, pyruvate, or the combination of these compounds. Supplementation with heat-inactivated catalase and acetic acid did not improve recovery of chlorine-stressed cells compared with recovery on nonamended media. Subsequent analysis of colonies from plates containing compounds which enhanced recovery indicated coliform verification percentages of greater than 80% on M-FC, greater than 90% on mT7, and greater than 94% on M-Endo media. These data suggest that the addition of peroxide-degrading compounds to various standard recovery media may improve detection of both coliform and heterotrophic bacteria in chlorinated waters. PMID- 2268163 TI - Identification and catabolic activity of well-derived gasoline-degrading bacteria from a contaminated aquifer. AB - Approximately 300 gasoline-degrading bacteria were isolated from well water and core material from a shallow coastal aquifer contaminated with unleaded gasoline. Identification of 244 isolates revealed four genera: Pseudomonas, Alcaligenes, Nocardia, and Micrococcus, with pseudomonads making up 86.9% of bacteria identified. A total of 297 isolates was sorted into 111 catabolic groups on the basis of aerobic growth responses on 15 gasoline hydrocarbons. Each test hydrocarbon was degraded by at least one isolate. Toluene, p-xylene, ethylbenzene, and 1,2,4-trimethylbenzene were most frequently utilized as growth substrates, whereas cyclic and branched alkanes were least utilized. Most isolates were able to grow on 2 or 3 different hydrocarbons, and nearly 75% utilized toluene as a sole source of carbon and energy. Isolates were remarkably specific for hydrocarbon usage, often catabolizing only one of several closely related compounds. A subset of 220 isolates was sorted into 51 groups by polyacrylamide gel electrophoresis. Pseudomonas aeruginosa was partitioned into 16 protein-banding groups (i.e., subspecies) whose catabolic activities were largely restricted to substituted aromatics. Different members of subspecies groups defined by protein-banding pattern analysis often exhibited different growth responses on the same hydrocarbon, implying marked strain diversity. The catabolic activities of well-derived, gasoline-degrading bacteria associated with this contaminated aquifer are consonant with in situ adaptation at the site. PMID- 2268164 TI - Two Penicillium camembertii mutants affected in the production of cyclopiazonic acid. AB - Penicillium camembertii was mutated and screened for cyclopiazonic acid-negative mutants. With a simple and rapid mini-extraction method for detection of cyclopiazonic acid production, we were able to isolate two strains which were affected in the production of this metabolite. One strain had completely lost the ability to synthesize detectable amounts of this secondary metabolite, whereas the other mutant produced 50 to 100 times less cyclopiazonic acid than the wild type. Also, the former strain had a changed morphology compared with the wild type. This morphological alteration appears to be coupled to the inability to produce cyclopiazonic acid because morphological revertants were able to synthesize cyclopiazonic acid to a level comparable to the wild type. The second mutant accumulated a new metabolite which was detectable by two-dimensional thin layer chromatography. This new metabolite, however, appears not to be a direct precursor of cyclopiazonic acid. PMID- 2268165 TI - Specific plate assay for bacterial heparinase. AB - A procedure was developed for detecting heparinase activity on heparin agar plates. The method is based on the differential precipitation of heparin and heparinase-generated heparin fragments by protamine sulfate. Heparinase activity is detected by the presence of clear zones against a white background. This method can be used to screen for the expression of recombinant heparinase and to identify Flavobacterium heparinum mutants expressing heparinase constitutively. PMID- 2268166 TI - Prolonged survival of Pseudomonas cepacia in commercially manufactured povidone iodine. AB - Pseudomonas cepacia organisms were recently recovered from a povidone-iodine antiseptic solution. During the subsequent investigation, laboratory studies were initiated to determine the survival time of these organisms in the iodophor solution, which contains 1% titratable iodine. The solution was sampled weekly upon receipt in our laboratory, and P. cepacia was subsequently recovered through 29 weeks of sampling. Current laboratory data and lot production date information from the manufacturer indicate that P. cepacia survived for up to 68 weeks from the time of manufacture. Scanning electron microscopic examination of contaminated solution demonstrated bacterial cells embedded in extracellular material. PMID- 2268168 TI - [Quantitative coronary angiography: methods, technics and usefulness]. PMID- 2268167 TI - Vibrios associated with red tides caused by Mesodinium rubrum. AB - Vibrios were isolated from red tides caused by Mesodinium rubrum and also throughout the year in the Ria de Pontevedra, Spain. The isolates were grouped into 14 phena by numerical toxonomy. Strains associated with red tides were restricted to four phena: phena I and II were Vibrio alginolyticus, and phena III and IV were Vibrio tubiashii and Vibrio anguillarum, respectively. V. anguillarum like strains (phena V through XI) predominated throughout the year outside the red tide areas. Cytotoxicity assays conducted in different poikilothermic and homoiothermic cell lines showed that cytotoxin production was not necessarily associated with the species selected during the red tides. PMID- 2268169 TI - [Experimental subendocardial postero-inferior infarctions]. AB - In 30 mongrel dog hearts, epicardial and thoracic unipolar records were obtained after myocardial damage was produced by infiltration of 96% alcohol in the postero-inferior free left ventricular wall. Necrosis was transmural in 5 cases, subendocardial in 11 and intramural in 10. In 4 dogs, intramural unipolar and bipolar leads were recorded in order to determine the electrical subendocardium and its relation to potentials of Purkinje's fibres. At the end of each experiment, left posterior subdivision block (LPSB) was provoked. In 90% of the cases, direct epicardial records were QS in transmural infarction, qrS or less frequently QRS in subendocardial ones, and rS or qRS in the presence of intramural necrosis. In several cases myocardial necrosis was located in the middle third instead of the inferior third, but the direct registries were similar. Nevertheless the surface leads (II, III and aVF) did not show abnormal Q waves or greater voltage of Q and S, but there were RS complexes in V1 and V2. In 80% of the cases, transmural necrosis of inferior third was manifested by QS complexes and subendocardial necrosis by rS or qRS complexes with increased Q and S waves and reduced R waves. LPSB masked the signs of necrosis. There is no justification for speaking of myocardial infarction with or without abnormal Q waves, because it does not add more precision. Moreover these expressions can create confusion in cases of middle or high posterior myocardial necrosis, revealed by RS complexes in V1 and V2. PMID- 2268170 TI - [Effect of dopamine on lung vascular mechanics. Its study in the isolated canine lobe model embolized with gel foam]. AB - After inducing an increase in pulmonary vascular resistance (Rp) in an isolated in situ lobe (LAIS) embolized with gelfoam (GE), the effect of dopamine infused at 12 mcg/kg/min in eight mongrel dogs was evaluated. We studied the rectilinear pressure-flow (QL/PL) relationship, the hemodynamic and blood gas before (condition A), 15 minutes later GE (condition B) and after dopamine infusion (condition C). After GE a decrease in QL and an increase in inflow (PL) and mean critical closing pressures (PLi) were noticed (p less than 0.01). Also decrease in pulmonary vascular conductance (1/Rp) was noted. At condition C a rise in QL and PL were noticed (p less than 0.01), but 1/Rp and PLi did not change. We concluded that dopamine in the LAIS with increased Rp at the used doses does not have vasoactive action for those vessels responsible for the phenomenons where flow resistance or mean critical closing pressure occurs. PMID- 2268171 TI - [Pharmacokinetics and antihypertensive effect of pelanserin in dogs ]. AB - Pelanserin pharmacokinetics were studied in six normotensive dogs after intravenous and oral administration. Additionally, the relationship between pelanserin plasma levels and its antihypertensive effect was studied in six hypertensive dogs after a single oral administration. Plasma level-time curves were fitted to an open two compartments model. Pelanserin bioavailability after oral dosing was about 30%, this could be due to a poor absorption from the gastrointestinal tract or to an important hepatic biotransformation by first pass effect. On the other hand, oral administration of pelanserin resulted in a significant antihypertensive effect that was not followed by tachycardia. Pelanserin plasma levels did not significantly correlate with the obtained antihypertensive effect. These results suggest that the observed effect was not only due to an action at peripheral level, but other mechanisms could likely be involved, probably with participation of the central nervous system. The pharmacokinetic and pharmacodynamic profiles of pelanserin allow to predict that this drug could have a place in the therapeutics of arterial hypertension. PMID- 2268172 TI - [The effects of histamine on the electrical and mechanical properties of the heart]. AB - The effects of histamine on the electrical and mechanical properties of the right and left atria and papillary muscle of the guinea-pig's heart were studied. The experiments were performed using conventional techniques of intracellular recording of the electrical activity and isometric tension. It was found that the distribution of the histaminergic receptors is different in the several tissues studied. The H2 receptors predominate in the right atrium, whereas the H1 in the left one. There are both kinds of receptors in the ventricular tissues. The main effects found were: a) In the right atrium: a positive chronotropic effect, a shortening of the action potential and an increase in excitability. b) In the left atrium only a shortening of the action potential was seen. The other electrical and mechanical parameters were not affected by histamine. c) In ventricular muscle a biophasic response in the action potential duration was observed, low concentrations of histamine induced a shortening of the action potential, whereas larger concentrations provoked a lengthening. Also low doses of histamine induced a negative inotropic effect, secondary to the activation of H1 receptors, while concentrations larger than 10(-8) M provoked a positive inotropic effect due to the H2 receptor activation. Also a decrease in excitability was seen mainly due to the activation of the H1 receptors stimulation. In every tissue studied the effects of histamine were seen with concentrations as low as 1 X 10(-10) M, being the H1 receptors who shown a greater affinity, since the activation of the H2 receptors were obtained only with doses larger than 1 X 10(-8) M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268173 TI - [Effects of cyproheptadine on the electrophysiological characteristics of the sinus node, ventricular myocytes and papillary muscles of the guinea pig heart]. AB - Cyproheptadine is an antagonist of S1 serotoninergic and H1 histaminergic receptors, with a well known cardiovascular activity, mainly vasodilation and a negative chronotropic effect. It has been suggested that cyproheptadine as other antiserotoninergic drugs act by blocking the calcium channel. In order to explore this possibility the actions of this drug were studied in several cardiac preparations: sinus node, isolated ventricular myocytes and papillary muscle from guinea-pig's heart. The experiments were performed using the conventional recording techniques of intracellular electrical activity and isometric tension. Doses from 0.25 microM to 1.0 microM were studied. The main findings were: in sinus node: a) inhibition of automatic activity, b) a decrease in the upstroke, c) a decrease in the plateau level, and d) a shortening of the action potential. In isolated ventricular myocytes: a) a decrease in the rate of depolarization, b) a decrease in the plateau level and c) a shortening of the action potential. In the papillary muscle: a) a decrease in tension and b) a shortening of the action potential. All the effects observed were dose dependent an agree with a blockade of the calcium channel. PMID- 2268174 TI - [Effects of the polyamines putrescine, spermidine and spermine on the hypertensive action of norepinephrine in anesthetized dogs]. AB - In anesthetized and vagotomized dogs, we investigate the associative effects on blood pressure of norepinephrine (NE) with the three polyamines putrescine (Pt), spermidine (Sd) and spermine (Se). Experimental series were performed under beta adrenergic blockade (propranolol 0.5 mg/Kg, iv.), alpha adrenergic blockade (phenoxybenzamine 15 mg/Kg, iv.), and under calcium antagonistic action (verapamil 0.3 mg/Kg, iv.). The three polyamines induced a potentiation on the hypertensive effect of NE, they change the dose/response curve to the left side in a potency rank of Se greater than Sd greater than Pt. Such potentiation was not different when a beta adrenergic blockade or calcium antagonism was present; however phenoxybenzamine neutralized it. On the other side, polyamines had a hypotensive effect when were administered alone to the animals. Such effect is related to a histamine releasing properties of the polyamines, and was abolished by previous administration of anihistaminic agents chlorpheniramine (5 mg/kg, iv.) and cimetidine (20 mg/Kg, iv.). In conclusion our results indicate that the potentiation of the hypertensive effect of NE by polyamines, could be attained through a mechanism which involves the alpha adrenergic receptors of the vascular smooth muscle but is not related to the calcium channels that show voltage dependence. PMID- 2268175 TI - [Silent myocardial ischemia in unstable angina and acute myocardial infarction. Prospective clinical study]. AB - To establish the prevalence and characteristics of silent myocardial ischemia in patients with unstable angina and acute myocardial infarction and its possible correlation with coronary artery lesions; two groups patients were studied, fifteen with unstable angina and fifteen with acute myocardial infarction. In all patients a continuous 24 hours ECG recording was made with a solid state microprocessor for ST variation analysis, and all underwent coronary arteriography and ventriculography, the severity of coronary heart disease was determined by Gensini scoring system and the coronary angiography morphology was studied. In 86% patients with unstable angina ischemic ST changes were found, 90% of these episodes were silent. There were 66% of the patients with acute myocardial infarction and ST ischemic changes of these 75% were silent. There was no correlation with the ischemic myocardium score index, nor with the angiographic morphology or the heart rate. Therefore it can be said that myocardial ischemia is a result not only of anatomic factors but of many others such as vasoconstriction, endothelial, myocardial, systemic and hemorheological alterations. PMID- 2268176 TI - [Discordance in the anatomy of the bronchial tree and atrial appendages]. AB - It is well known, that in complex congenital heart disease, the bronchial anatomy reflects the atrial situs in the majority of patients. Few exceptions to this rule have been reported in the literature. We report four patients in whom we found discordance between the anatomy of the bronchial tree and the external aspect of the atrial appendages. Two patients had bronchial situs solitus with atrial levoisomerism, the third patient had bronchial levoisomerism with atrial situs solitus and in the fourth one we found inverted bronchial anatomy with levoisomerism of the atrial appendages. In three patients, broncho-atrial discordance was diagnosed clinically by bronchial tomography and selective atrial angiography, and in the other one the diagnosis was made by anatomical study. In this last patient, external atrial anatomy was found to be of levoisomerism, with an internal atrial aspect of situs inversus. Prediction of atrial arrangement by bronchial anatomy retains its diagnostic value. However, it is necessary to bear in mind that exceptions do exist. It is discussed how to suspect these exceptions, and the final diagnostic conduct is indicated. PMID- 2268177 TI - [The utility of color Doppler in dissecting aortic aneurysm]. AB - We inform about the utility of Color-Doppler to identify dissection in aortic aneurysm. We studied five patients, fourth with dissection and one without dissection. All of them were in the fourth decade of life, except the patient without dissection, who developed symptoms at the age of 62. Two-dimensional echocardiography displayed the alterations of the aorta, such as dilatation of the walls, the presence or absence of dissection and in the cases with dissection the extension of it (three patients had DeBakey Type I, one DeBakey Type III an other DeBakey Type II). In all patients with dissection the Doppler study determined the presence or absence of flow through the false channel, in particular in the second and fifth patient and with Color-Doppler we observed that the flow was bidirectional. Also the degree of aortic incompetence could be quantified. It is concluded that with two-dimentional echocardiography it is possible to identify the anatomical features of aortic aneurysm and that Doppler study gives additional hemodynamic information which has importance in therapy and prognosis. PMID- 2268178 TI - [Transesophageal echocardiography. General principles and applications]. AB - A new echocardiographic technique is described, which allows cardiovascular ultrasonic exploration by means of a transducer mounted on the distal tip of a gastroscope. The transducer is moved along the esophagus and from time to time into the stomach, which permits real-time visualization of the different cardiac segments and the great arteries. This technique is of special utility in the exploration of posterior structures as are the left atrium and its appendage, the pulmonary veins, etc. The most important views in the transverse plane are described, as well as the technical aspects, the limitations and the possible complications. PMID- 2268179 TI - [The importance of radiology in the localization of pheochromocytoma]. AB - The usefulness of different radiologic studies in localizing the tumor was evaluated in 26 patients with a firmly established diagnosis of pheochromocytoma. The site of the lesion was correctly identified in 8% of the cases by the plain abdominal x-ray films: in 11% by the plain thoracic films; in 34% by uronephrotomography; in 88% by angiography and in 6 patients (100%) in whom computed tomography scans (CT) were performed. The tumors were intra-adrenal in 19 patients and extra-adrenal in the remaining 7 cases. Of the latter, two were found in the organ of Zuckerkandl, two were abdominal para-aortic, two others in the para-aortic region of thorax, and one with intra an extra-adrenal tumors. It is concluded that CT scans are quite successful in preoperative localization of pheochromocytoma. The non-invasive nature of the technique makes it the method of choice in the anatomical localization of this type of tumors. PMID- 2268180 TI - Cerebellar localization and colocalization of GABA and calcium binding protein D28K. AB - Immunocytochemical studies using antibodies raised against the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) and against the 28 Kd vitamin D dependent calcium binding protein (calbindin) in the cerebellum, are reviewed. The GABA immunoreactive neurones found in the cerebellar cortex were the Purkinje cell (PC), the three classes of intrinsic inhibitory interneurones, stellate, basket and Golgi cells and the cells of Lugaro. Some of the neurons of the cerebellar nuclei were also found to be GABA immunoreactive. A part of these could be identified as extrinsic neurones projecting either back to the cerebellar cortex, or to the inferior olive, both these pathways being topographically highly organized but arising from independent parent neurons. The presumed inhibitory function of these two pathways are discussed. Calbindin immunoreactivity in the cerebellum was confined to the PCs, staining concerned the whole cell including soma, branching dendrites, axons and axons terminals. The antibody, which appears to be tightly bound to the PC in vivo, failed to stain some of the PC when cerebellar slices maintained in vitro were studied. The stability of the antigen-antibody binding and the use of calbindin as a marker specific for the PC in the cerebellum, is discussed. Co-localization of GABA with calbindin as well as with other calcium binding proteins are reported to be found in the PCs. While these co-localizations have led to much speculation, conclusive functional roles for them have not been identified at present. PMID- 2268182 TI - Topographical localisation in the projections from the inferior olive to the paravermal cortex of the anterior lobe and paramedian lobule in the cerebellum of the cat. A brief review. PMID- 2268181 TI - Early development of the rat precerebellar system: migratory routes, selective aggregation and neuritic differentiation of the inferior olive and lateral reticular nucleus neurons. An overview. AB - The migration, cytoarchitectonic segregation and neuritogenesis of the inferior olive (ION) and lateral reticular (LRN) neurons are described in the rat. Generated in the same primary precerebellar neuroepithelium, at embryonic days 12 13 (E12-E13) for the ION and E12-E14 for the LRN, the postmitotic cells take either the intraparenchymal (smms, for ION neurons) or the subpial migratory streams (mms, for LRN neurons and other populations, as those of the external cuneate nucleus, ECN). The ION neurons settle in their ultimate domain from E16 to E18, ipsilaterally to their proliferation side. The LRN (and ECN) neurons cross the midline at the "floor plate" (FP) level, and settle contralaterally to their birthplace between E17 and E19. In both cases, the acquisition of a mature dendritic tree is a late event when compared to the precocious axonogenesis. The FP structure may play a major role in i) attracting the axons of the precerebellar neurons, and ii) instructing these neurons whether to cross the midline or not. Thus, ultimately the FP may govern the pattern (crossed or uncrossed) of the projections of the ION and LRN to their common cerebellar target. PMID- 2268183 TI - Visual inputs to the dorsocaudal fastigial nucleus of the cat cerebellum. An experimental study using single unit recordings and horseradish peroxidase labelling. AB - Visual afferents to the cat fastigial nucleus (FN) have been studied with single unit recordings and horseradish peroxidase techniques. A total of 158 cells responding to electrical stimulation of the optic chiasm (OCh) were extracellularly recorded from the dorsocaudal part of the FN. They were classified into three groups: type-1 cells (48%) which showed early suppression and late facilitation; type-2 cells (38%) which showed early facilitation and late suppression; type-3 cells (14%) which exhibited long lasting suppression with no signs of facilitation. Eight of 32 cells tested showed the same response patterns to photic stimulation as to electrical stimulation of the OCh. None of the cells responding to electrical and photic stimulation, however, were found in the rostral and ventral parts of the FN. Furthermore, 29 cells which responded to electrical stimulation of the OCh were tested for responses to moving pattern stimulation. Seven (4 type-2 cells and 3 type-3 cells) of the 29 cells showed clear modulation, reflecting the velocity component of a horizontally moving pattern. However, none of 13 type-1 cells tested exhibited apparent modulation in relation to movement of the pattern. In order to trace the possible pathways mediating visual signals to this part of the FN, the horseradish peroxidase (HRP) method was used. Injection of HRP into the caudal FN resulted in the labelling of many cells, predominantly in the medial (M) and the descending (D) vestibular nuclei and in lobules VI and VII of the cerebellar vermis. A series of experiments further indicated the presence of possible pathways propagating visual signals to the caudal FN. The main routes are: 1) via the nucleus of the optic tract (NOT)--the dorsal part of the medullary reticular formation--the M and the D vestibular nuclei--to the FN, and 2) via the superior colliculus--the pontine nuclei--vermal lobules VI and VII--to the FN. The different physiological response patterns of FN cells may indicate that several types of visual signals involved with visually guided movements impinge upon the dorsocaudal FN. PMID- 2268184 TI - Dentate control pathways of cortical motor activity. Anatomical and physiological studies in rat: comparative considerations. AB - The dentato-thalamocortical projections have been studied in albino rats using anatomical and physiological approaches. The anatomical analysis reveals that the dentatothalamic input to the ventral thalamus and the thalamocortical projection from this region onto the motor cortical area have a complex topographical arrangement. The corticothalamic reverberating pathways, both direct and through a relay in the nucleus reticularis thalami, are also roughly arranged in register with the same topographical pattern. This arrangement has been reconciled with that of the motor cortex, as determined by the motor effects of intracortical microstimulations. From this is inferred a somatotopical arrangement of the cerebellar nucleus lateralis, or dentate. These observations are confirmed by the results of our physiological analysis. The movements obtained with direct microstimulations of the nucleus lateralis affect either one joint (simple movements) or, more seldom, several joints (complex movements) of the same limb. A rough rostrocaudal arrangement is found in the nucleus lateralis: the caudocentral regions of the nucleus contain the representation of the musculature of forelimb and head, whereas the hindlimb is represented in the rostralmost part of the nucleus. A more complex organization is found to be related to the three cytoarchitectonic subdivisions of the nucleus lateralis. The main, large-celled part of the nucleus is engaged in the control of the large skeletal musculature. The dorsolateral hump is involved in mouth and peri-oral activities. The ventral, parvocellular, subnucleus is involved in fine exploratory movements of vibrissae, eyes, and forelimb wrist and fingers. The implication of the dentato thalamocortical pathways in the cortical motor activities in the rat is discussed with attention to the dentate control of the "voluntary" motricity in primates. PMID- 2268185 TI - The significance of foliation and fissuration of cerebellar cortex. The cerebellar folium as a fundamental unit of sensorimotor integration. AB - I propose the general hypothesis that each individual folium in the cerebellum is an integrative module that is involved in unique sets of sensorimotor transactions. Although the basic types of operations carried out by cerebellar cortex may be similar in all folia, the mosaic of afferent sources, intrinsic organization and efferent destinations appear to be unique for each folium. I believe that this conception is supported by: 1) comparative data which illustrate species-typical folial patterns, 2) neuroanatomical data which reveal not only different structural features of folial crowns and fundi, but differential afferent and efferent connectivity of different folia as well, 3) physiological data, which demonstrate unique patterns of afferent activity in different folia, and especially by 4) ontogenetic data which establish that each folial crown expands and differentiates into an architecturally distinct cortical entity. Taken together, all these lines of evidence suggest that the numbers and patterns of folia exhibited by the cerebellar cortex of different mammals are morphological indicators of differential organization of sensorimotor control functions in each animal. Even intraspecific individual variations in folial number, size and pattern may signify structural-functional determinants of some individual differences in sensorimotor transactions. Since so little research has addressed the many testable ideas embodied in these general hypotheses, it seems to me that neuroscientists have a long way to go to clarify how the many different folia and lobules of cerebellar cortex actually function in the common, everyday, orderly, dynamic and ongoing reflex, postural, learned and deliberate behavioral sequences that characterize the normal behavioral repertoires of different animals. The enormous advances in understanding brought forth by the extensive research and writings of Professor Brodal and his colleagues have expanded our horizons to avail us of an enormous range of new vistas into cerebellar functional morphology. It is now the task of neurobiologists to explore these diverse new domains in ever greater depth and detail. PMID- 2268186 TI - Structural-functional organization of cerebellar and vestibular systems. PMID- 2268187 TI - [Changes in human cerebral cortex in various areas of concussion in severe cranio cerebral injury]. AB - In 23 patients with a severe cranial-cerebral trauma the operative material (pieces of the cortex, obtained from the destructive, transitional and relatively preserved zones in the bruise foci with crushing, localized in various lobules of the cerebral hemispheres) has been studied. From 2 h up to 9 days after trauma, changes, characterizing the state of the vascular bed, nervous and glial cells have been followed. In the external area of the transitional zone in 15 patients and in the relatively preserved zone in all the patients reversibly altered nervous cells predominate. Only in the destructive zone in all 23 patients and in the whole transitional zone in 8 patients neurons in all cortical layers are deeply injured and unviable. Certain considerations on differential surgical tactics, when treating the bruise foci with crushing at a severe cranial and cerebral trauma are presented. PMID- 2268188 TI - [Cholinergic pyramidal neurons of the motor region of human neocortex]. AB - By means of histochemical methods for revealing +choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) cytoarchitectonic of the field 4 of the motor cortex of the cerebrum has been studied in 5 persons at the age of 33-65 years. An essential part of neurons at revealing AChE and most of them at revealing ChAT do not react. Among giant pyramidal neurons (Bets) according to ChAT activity, 4 types are distinguished: neurons with low, middle, high and very high activity. The presence of ChAT is ascertained in middle and large pyramidal neurons of the III layer. Presence of ChAT-positive synapses is demonstrated in apical dendrites. A conclusion is made that less part of the pyramidal in the III, V layers are cholinergic ones. PMID- 2268189 TI - [Ultrastructure of the parietal region of the brain after selective damage of the serotoninergic system]. AB - The selective lesion of the afferent serotoninergic system by means of intracisternal administration of 5,7-dihydroxytryptamine produces certain structural rearrangements in a part of cellular elements and in various parts of the neuropil of the neocortical parietal area. The deficiency of serotoninergic innervation influences the metabolic processes. This is evident from the change in the structure of protein synthesizing apparatus in a number of postsynaptic neurons. It is possible that the structural rearrangements observed in the serotoninergic and in the conjugated to it mediatory systems make the base of functional disorders in the neocortex and are accompanied with certain changes in the integrative activity of the brain. PMID- 2268190 TI - [Embryonal development and the structure of the intermesenteric plexus in humans and various mammals]. AB - The intermesenteric plexus is an independent formation, it is connected with other plexuses in the abdominal and pelvic cavities and participates in innervation of organs. In the species investigated (mole, rat, cat, dog, man) connections between the intermesenteric and other vegetative plexuses in the abdominal and pelvic cavities vary according to their amount and complexity, they are most abundant and complex in man. In the latter the plexus is also mostly rich in neuro-fibrillar and neuro-cellular elements. In the intermesenteric plexus of the man and the animals studied there is a rather big part of vegetative ganglia, which can be considered as peripheral centers of the internal abdominal organs innervation. PMID- 2268191 TI - [Evolution of the locomotor-sensory systems]. AB - Among directing physical factors of evolution of the locomotor-sensory system (LSS) gravitation, photons energy, oscillations of water and air media, ligands play the main role. At the molecular level the LSS elements are formed on the base of synthesizing genes that bring about development of protein molecules of tubulin and specific protonizing proteins in composition of the locomotor apparatus in Procariota flagellas. Tubulin and dinein with ATPh-ase activity are included in the flagella composition of LSS in Eukaryota, actin and miozin--with a high ATPh-ase activity--in composition of LSS myofilaments in ameboid Eukaryota and locomotor musculature in Metazoa. Simultaneously, in Pro- and Eukaryota in the same cell sensory molecules of rhodopsin, mechanoreceptors, chemoreceptors and so on can be synthesized. As a rule they localize in the flagellar membranes. In Metazoa single receptory flagellar cells are differentiated; they realize conservatively some receptive molecules that are already prepared by their ancessors--Eukaryota. The molecules also preserve their localization in the flagellar membranes. In Metazoa two types of locomotion take place according to the function of regulatory genes: initial flagellar and muscular definitive apparatus. Both types of locomotion are directed and regulated by the organs of sense and CNS; they form a strict spatial model of fixated synaptic connections of LSS. For the first time it was discovered in Ctenophora. This model, despite a complicated organization, is conservatively preserved in its general form in all Proto- and Denterostomia. PMID- 2268192 TI - [Structure of the adrenal glands of Greenland seal Pagophilus groenlandica Erxleben, 1777 (Phocidae)]. AB - The harp seal adrenal gland studied is alike that of terrestrial mammals, but has some peculiarities. Firstly, this is presence of the fetal cortex in the adrenal gland without any signs of involution and degeneration in adult animals. This phenomenon has been previously described only for the horse adrenal gland. The glomerular zone of the cortex peculiar for the adrenals in the terrestrial mammals in the species studied has the form of arches. This property is also characteristic only to the horse gland. The absence of intermediate and juxtamedullary zones also differs the harp seal adrenal gland from that of terrestrial mammals. PMID- 2268193 TI - [Local characteristics and interrelations between glands and lymphoid conglomerations in the esophageal wall]. AB - Proper glands in 248 total preparations and lymphoid accumulations in 112 preparations have been investigated macro-microscopically in the human oesophageal preparations at various age. The organs have been obtained from 152 corpses of persons died from the death by violence and having no pathological changes in the organs of digestive and immune systems. The lymphoid tissue in the oesophageal wall is presented as accumulations of cells (prenodules++) and as diffusely scattered immune-competent cells. The glands and lymphoid accumulations are oriented as longitudinal rows. The lymphoid tissue accumulations are situated near to the glandular ducts, because the latter can serve as pathways for penetrating antigenic material into the organ's wall. The amount of the glands is maximal mature and elderly age, and that of lymphoid accumulations--at the second childhood. The dimensions of the gland body increase in the cranio-caudal direction, while the lymphoid accumulations, just the reverse, have their maximal dimensions in the upper third of the oesophagus. The gland bodies in places of the organ's anatomical narrowings in the section have more alveoles and are situated nearer to the covering epithelium than the glands in the neighbouring areas of the wall. PMID- 2268194 TI - [Microscopic anatomy of small-intestinal lymphoid patches in children and adults]. AB - Longitudinal histological sections of lymphoid patches (LP) in the small intestine, stained after van Gieson and with hematoxylin--eosin, obtained from 105 corpses of persons at the age of 0 up to 90 years have been studied. The LP parenchyma is presented as accumulation of lymphoid nodules++ with a germinative center, or without it and diffuse lymphoid tissue. The lymphoid nodules++ situate both in the mucous membrane and in the submucous tela of the small intestine. The area of the LP components in the newborns is the greatest--84% from the whole area of the LP section. During the human life it decreases and by the old age it makes 47%. The lymphoid nodules++ area with the germinative center in the newborns makes 21% from the area of the LP section, in children from 1 to 3 years of age it increases up to 50%, then it gradually decreases and in the elderly age it makes only 3.8%. The diffuse lymphoid tissue in the LP composition is revealed in all age periods. Size of the lymphoid nodules++ patches, situating in the jejunum and ileum walls in the newborns is the same. In children at the age of 10 days--12 years the LP nodules++ in the ileum are larger than those in the sejunum. The size of the LP noduli increase up to the period of the second childhood then decreases. The height of the lymphoid noduli in persons of mature, elderly and old ages decreases twice in comparison with the children of 3-12 years of age. PMID- 2268195 TI - [Ultrastructure of the renal corpuscle of fresh water fishes]. AB - By means of light (semithin slices) and electron microscopes structural organization of the corpuscle and glomerulus of the capsule has been studied in freshwater fishes--carp (Cyprinus carpio) and crucian carp (Carassius carassius). The diameter of their glomeruli are in the carp from 80.8 +/- 1.4 mcm up to 59.8 +/- 2.4 mcm and in the crucian carp--from 86.4 +/- 1.8 mcm up to 69.25 +/- 0.2 mcm. Between these dimensions there are significant differences. Components of the external wall of the capsule in the fishes studied have similar structure. In epitheliocytes, situating on the basement membrane, electron opaque inclusions have been revealed. They resemble, by their ultrastructure, granules of peripolar cells, described in mammals and in man. In places, where epitheliocytes have contacts, thin folds are formed, they turn into the capsule lumen. Touching the cell surface, they can form border vacuoles. The main peculiarity of endotheliocytes in the glomerular capillaries is presence of diaphragmated and open fenestrae (their size is from 30 to 50 nm) in the peripheral zone of their cytoplasm. Unlike the higher vertebrates, the fishes have a well developed pericapillary mesangium. It contains mesangial matrix and rare processes of mesangiocytes. PMID- 2268196 TI - [Anatomo-echocardiographic comparisons as a method of increasing the informative value of two-dimensional echocardiograms]. PMID- 2268197 TI - [Evaluation of informative value of the slices--a way of the optimal studies of the brain]. PMID- 2268198 TI - Paternity leave: the right to share the care. PMID- 2268199 TI - Establishing a professorial nursing unit. PMID- 2268200 TI - Another way of caring. PMID- 2268201 TI - Cord care appraised. PMID- 2268202 TI - Erythropoietin. PMID- 2268203 TI - The asthma management plan: a nursing perspective. The National Asthma Campaign Committee. Roual Australian College of Practitioners. PMID- 2268205 TI - Women and AIDS. PMID- 2268204 TI - HIV/AIDS: genesis of a national training program. PMID- 2268206 TI - Due recognition. Interview by Natalie Newman. PMID- 2268207 TI - Complexities in the management of arterial compromise due to thoracic outlet syndrome. AB - A patient with arterial compromise secondary to thoracic outlet obstruction is presented and discussed. The case highlights the difficulty in management when initial surgery does not adequately decompress the outlet. It also demonstrates the risk to limb viability that may ensue. PMID- 2268208 TI - Effects of publishing multiple-choice questions on their subsequent item analysis. AB - A prospective study was carried out to determine what effects publication within a multiple-choice question (MCQ) book of 63 selected items from a bank had on their performance in subsequent examinations. A closely corresponding group of 63 unpublished questions set both before and after publication of the book was used as control. The specific outcomes studied were those on facility index, r biserial discriminating index and differences in performance between abler (upper 25%) and weaker (lower 25%) candidates. The mean facility index of the published questions increased significantly (P less than 0.01) after publication, while no significant change was observed in the mean facility index of control questions (P greater than 0.05) or in the mean discriminating index of published (P greater than 0.05) and control (P greater than 0.05) questions. Contrary to expectations the mean facility index of published questions increased, after publication, to a greater extent (P less than 0.01) for abler candidates than for weaker candidates. The study supports the hypothesis that publication of questions from a bank makes them easier to answer. The practice of adjusting the cut-off mark for passing according to the proportion of published questions in a given examination, however, is not justified. The findings highlight the need to advise less able candidates to make greater use of the MCQ book in preparing for an examination. PMID- 2268209 TI - Anastomosis: a craft workshop for surgical trainees. AB - Surgery is a very personal exercise and no two surgeons use an identical technique. Traditionally, operative expertise has been acquired through a system of apprenticeships. Pettigrew has shown that operative performance is the main factor in determining postoperative complications and therefore the length of hospital stay, and surgical journals have recently returned to technique as a topic of debate. Certain skills, such as knot tying, can be learned and tested outside the operating theatre, and this has been extended to craft workshops dealing with more complex procedures, including fracture fixation. This article describes an anastomosis workshop held in New Zealand recently for general surgical trainees. PMID- 2268210 TI - Results of primary tendon repair with closure of the tendon sheath. AB - This study reports the results of primary flexor tendon repair combined with closure of the tendon sheath in 31 Zone 2 injuries. In 3 digits, the profundus tendon alone was divided. In a further 7 digits, one tendon was completely divided and the other was incompletely divided. The remaining 21 digits involved complete division of both tendons. Assessment of the results according to the total active motion (TAM) system found 86% of the repairs in the excellent, good and fair categories. Two ruptures occurred (6%). A second assessment employed the criteria of Strickland, excluding the motion of the metacarpophalangeal joint. The results obtained following suture of both tendons were: excellent (39%); good (36%); fair (14%); poor (4%); and rupture (7%). These results lend support to the belief that closure of the tendon sheath decreases external adhesion formation and improves motion without increasing the risks of rupture. PMID- 2268211 TI - Trauma triage in western Sydney: results of a pilot study. AB - A pilot study of the effectiveness of prehospital triage of trauma patients was carried out in a western Sydney between February and July 1988. Triage guidelines were developed to identify seriously injured persons at the incident site who might warrant admission to a Level 3 Trauma Service Hospital (Trauma Centre), as part of the NSW Department of Health trauma services plan. The study results were based on 64% of ambulance trauma transports for which a triage decision was provided. Of trauma transports studied, 3.7% had injuries serious enough to warrant admission to Level 3 Trauma Service Hospital. Ambulance officers correctly triaged 77% of these cases in the field. However, 62% of trauma transports triaged 'severe' or 'critical' did not have injuries serious enough to warrant admission to a Level 3 Trauma Service Hospital. Nevertheless, the triage guidelines compared favourably with similar instruments used elsewhere. Based on the performance of the triage guidelines it was concluded that the introduction of a regionalized trauma service in metropolitan NSW with local bypass is possible. PMID- 2268212 TI - Initial experience of intra-operative red cell salvage. AB - The use of red cell saving machines is described in 16 cases of aortic reconstruction. There were 3 deaths in the series, all unrelated to use of the technique. Salvaged autologous blood accounted for 45% of red cell requirements. Biochemical and haematologic parameters were monitored before, during and after operation. When large volumes of blood are salvaged, the system becomes cost effective and the risks of homologous transfusion are reduced. PMID- 2268213 TI - Aortic aneurysm surgery in the presence of a horseshoe kidney. AB - A review of three cases of aortic aneurysm in association with a horseshoe kidney is presented. Both the transperitoneal and retroperitoneal approaches to the aneurysm are detailed and the relative advantages and disadvantages outlined. The conventional approach of transection of the renal isthmus is not recommended because of the possibility of damage to the collecting system of the horseshoe kidney. The place of specialized investigations is outlined. PMID- 2268214 TI - Desmoplastic, neural transforming and neurotropic melanoma: a review of 45 cases. AB - An analysis of the clinicopathological features of 45 cases of desmoplastic, neural transforming and neurotropic melanoma assessed by a single pathologist are reported. The age range of 27 males and 18 females was 17-88 years. Twenty primary lesions (44%) were on the head and neck and fourteen (31%) were on the trunk. Thirty lesions (67%) were amelanotic. The initial clinical diagnosis was incorrect for 16 patients. Mean thickness was 4.5 mm. Recurrence occurred in 17 patients (38%). Local recurrence has occurred in 12 patients. This was related to a primary where: pathological diagnosis was incorrect; excision was less than 1 cm; the site was on the head and neck; Clarke level was V; and Breslow thickness was greater than 4 mm. Four patients had cranial nerve neuropathies due to recurrent neurotropic melanoma. Four patients are alive with inoperable disease and five have died from disseminated melanoma. These tumours can be difficult to recognize clinically and pathologically, with poor results if not adequately treated primarily. Therefore, the need for surgeons to be aware of this tumour and its clinicopathological features is important. Close follow-up is essential. PMID- 2268215 TI - Pancreaticojejunostomy versus pancreaticogastrostomy in reconstruction following pancreaticoduodenectomy. AB - Nineteen consecutive patients, 7 male and 12 female, underwent pancreaticoduodenectomy for malignancy during the 3-year period 1985-88. The pancreatic remnant in the first 12 patients (Group I) was managed alternately by pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). Patients undergoing PJ and PG (6 each) were comparable in age, biochemical parameters and nature and extent of disease. Three patients, all in the PJ subgroup, died (25% mortality) due to pancreatic leak, biliary leak and hepatocellular failure. In view of the high complication rate following PJ, the remaining 7 patients (Group II) underwent PG. For patients undergoing PG, the hospital stay was shorter, complications were fewer and there was no anastomotic leak or death (0% mortality). This study represents the first attempt at comparison of PJ with PG in reconstruction following the Whipple procedure by the same team. The results suggest that PG deserves wider application. PMID- 2268216 TI - Detection of articular defects using magnetic resonance imaging: an experimental study. AB - This study evaluates magnetic resonance imaging (MRI) in the detection of surgically created articular defects in bovine knees. A total of 26 articular defects was created in 2 fresh cadaveric cows' knees. The defects created include chondromalacic grade 2 defects, chondral and osteochondral defects from 3 to 15 mm in diameter. The knee joints were repaired in a normal saline bath to exclude air in the joint prior to MR scanning. T1 weighted spin echo (SE) images and 3D gradient echo (FISP 40 degrees 3D) images were obtained. The T1 weighted SE imaging technique detected 15 defects (57.7%) compared with FISP 3D imaging technique detection of 17 defects (65.4%). The two techniques combined enable 21 of 26 defects (80.8%) to be detected. The imaging techniques used in this study were not able to detect chondromalacic defects less than 10 mm in diameter, nor chondral defects less than 5 mm in diameter. However, small osteochondral defects of 3 mm in diameter are detectable provided the depth of the defect is not less than 10 mm. The FISP 3D imaging technique alone is more sensitive in detecting chondral defects. Both imaging techniques have similarly high sensitivities in detecting osteochondral defects. The imaging time for combined T1 weighted SE and FISP 3D sequence is short (16.5 mm) and this combined technique may be useful for MR scanning of knee joints suspected to have articular defects. PMID- 2268217 TI - In situ saphenous vein bypass: technical aspects and results. AB - A consecutive series of 113 non-reversed saphenous vein grafts is presented to illustrate the technique of the procedure, modifications necessary to overcome its disadvantages and the results obtainable using such methods. The grafts were performed between January 1986 and January 1989. During this period vein utilization rate rose to more than 90%. Eighty-one procedures were performed for limb salvage (mean preoperative ankle pressure index: 0.32 +/- 0.16). Cumulative patency at 30 months was 88% (+/- 4%) for the 81 limb salvage procedures and 89% (+/- 3%) for the total 113 grafts in the series. Twelve grafts permanently failed. No graft has failed after 2 months. Amputation was avoided in 88% of limb salvage procedures. Operative mortality was 4.4%, the average age of those dying being 77 years. Fifty-three in situ grafts were followed prospectively after accurate mapping of their valve lysis was performed during surgery. Patterns of valve lysis and technical aspects related to the performance of in situ grafts will be presented. PMID- 2268218 TI - Hide and seek: pre-operative ultrasonic localization of non radio-opaque foreign bodies. AB - Ultrasound has long been used as a diagnostic and therapeutic tool in surgery. We have extended its use to hand surgery, where is has several applications. Non radio-opaque foreign body extraction is invariably a frustrating exercise of 'hide and seek'. Accurate pre-operative localization with ultrasound illustrating size, shape, depth, soft tissue and bony relationships can ensure rapid and complete removal. Several cases are presented to demonstrate the use of ultrasound for the detection of non radio-opaque foreign bodies. The technique used will be described. We feel pre-operative localization by ultrasound is a useful technique to assist with the removal of non radio-opaque foreign bodies. PMID- 2268219 TI - Acute flexor tenosynovitis caused by Streptococcus pneumoniae. AB - A case of acute flexor tenosynovitis caused by Streptococcus pneumoniae in a previously well male truck driver is described. The importance of specimen collection and processing in establishing a microbiological diagnosis is emphasized. Early surgical drainage and treatment with penicillin resulted in rapid resolution of the infection and a return to full function of the hand. PMID- 2268220 TI - Limy bile cholecystitis: an in vitro study and a case report. AB - Limy bile is a rare condition characterized by excessive precipitation of calcium carbonate in the gall-bladder. It has been found to cause cholecystitis without obstruction at the neck of the gall-bladder. A patient with the appearance of limy bile on ultrasound films which was consistent with a large gallstone is described. An in vitro study with gall-bladders filled with lime utilizing ultrasonography is also presented for the first time. PMID- 2268222 TI - Muscle metabolism. PMID- 2268221 TI - Introduction to the functional anatomy of the mammalian motor unit. PMID- 2268223 TI - The response of muscle to enhanced and reduced activity. PMID- 2268224 TI - Muscle metabolism during fatigue and work. AB - Metabolic fatigue is a characteristic muscle response to intense exercise that has outstripped the rate of ATP replacement. The accumulation of metabolic by products, namely hydrogen ions and diprotonated phosphate, interferes with actin myosin interaction, effectively preserving muscle ATP levels by preventing further ATP hydrolysis. Muscle force and metabolite concentrations return to normal in about 5 minutes. Less intense exercise causes a more subtle, non metabolic fatigue due to a still-undefined disturbance of excitation-contraction coupling, which can last for several hours. In this type of fatigue, greater effort is required to generate submaximal forces. Endurance exercise is mainly limited by the size of muscle glycogen stores and how efficiently they are used. Endurance training permits an athlete to work aerobically at high rates, consuming a mixture of lipid and carbohydrate fuels. When muscle glycogen is used up, exercise can only continue at the relatively low rate supportable by lipid metabolism. Anaerobic exercise is also limited by subjective factors such as dyspnoea and muscle pain, which have objective determinants. Extremely prolonged exercise can lead to general collapse because of dehydration, hyperthermia, or hypoglycaemia. None of these factors explains the phenomenon of asthenia, a subjective sense of exhaustion that produces no objective impairment of physical performance. The metabolic myopathies are experiments of nature that promise to shed new light on the biochemical basis of muscle fatigue. This will require quantitative studies of the kind provided by topical magnetic resonance spectroscopy, correlating physiology and metabolism in vivo. PMID- 2268225 TI - Protein turnover and amino acid metabolism in human skeletal muscle. PMID- 2268226 TI - Normal metabolism and disorders of carbohydrate metabolism. PMID- 2268227 TI - Mitochondrial oxidations and ATP synthesis in muscle. PMID- 2268228 TI - Defects of fatty-acid oxidation in muscle. AB - Long-chain fatty acids (LCFA) are oxidized by muscle mitochondria after transport in the cytosol by fatty-acid-binding protein(s) and their activation by a thiokinase. Carnitine, two forms of carnitine palmitoyltransferase(s) and carnitine acylcarnitine translocase are involved in LCFA gating. A primary genetic carnitine deficiency occurs in children with dilated cardiomyopathy, hypoglycaemia and low carnitine content in plasma, liver and muscle, owing to a defect in a common high-affinity transport system. This high-affinity transport in muscle differs from a low-affinity transport that has modifications during muscle maturation. The genetic enzyme defects of beta-oxidation (long-chain acyl CoA dehydrogenase, medium- and short-chain acyl-CoA-dehydrogenase) present with Reye-like attacks that may lead to non-ketotic hypoglycaemia, coma and sudden infant death syndrome. There is elevated urinary excretion of dicarboxylic acids, acylcarnitines and acylglycines. Secondary carnitine deficiency may occur. ETF and ETF dehydrogenase deficiencies may present in a neonatal form with congenital anomalies, or in a later-onset form with ethylmalonic adipic aciduria. A still unidentified defect leads to LCFA accumulation in fibroblasts, bone marrow, liver and muscle cells in a multisystem triglyceride disorder. PMID- 2268230 TI - Introduction to the toxicology of muscle. PMID- 2268229 TI - The genetics of metabolic disorders of muscle. PMID- 2268231 TI - Histamine uptake by human normal neutrophils in vitro. AB - The uptake of different concentrations of (2.5-3H) histamine by normal human neutrophils at 37.5 degrees C in a tris-albumin buffer was determined at 20, 60 and 90 min of incubation. Uptake was correlated with the concentration of amine and incubation time with a saturation-like curve. On the basis of these results, it is suggested that neutrophils play a role in the regulation of histamine plasma levels. PMID- 2268232 TI - Non-specific binding of immunoglobulins and protein A-Gold complex with cytoplasmic granules of human mast cells. AB - A non-specific staining of mast cells by a number of proteins and immunoglobulins has been observed using different immunocytochemical techniques and different antisera at light and electron microscopy level. This finding has been related to an ionic binding of cationic charges, such as aminic groups with an high pI, to the strongly anionic residues of mast cell granules. This hypothesis is supported by the lack of non-specific binding achieved using negatively charged chromogens (i.e. FITC--or Rhodamine-conjugated antibodies) or using cationic dyes before the immunohistochemical reaction. It is therefore stressed that adequate and accurate negative controls must always be carried out in order to get correct interpretations of the staining results. PMID- 2268233 TI - Research on neutron beam design for BNCT at the Musashi Reactor. PMID- 2268234 TI - Neutron beam studies for a medical therapy reactor. AB - A conceptual design of a Medical Therapy Reactor (MTR) for neutron capture therapy (NCT) has been performed at the Idaho National Engineering Laboratory (INEL). The initial emphasis of the conceptual design was toward the treatment of glioblastoma multiforme and other presently incurable cancers. The design goal of the facility is to provide routine patient treatments both in brief time intervals (approximately 10 minutes) and inexpensively. The conceptual study has shown this goal to be achievable by locating an MTR at a major medical facility. This paper addresses the next step in the conceptual design process: a guide to the optimization of the epithermal-neutron filter and collimator assembly for the treatment of brain tumors. The current scope includes the sensitivity of the treatment beam to variations in filter length, gamma shield length, and collimator lengths as well as exit beam aperture size. The study shows the areas which can provide the greatest latitude in improving beam intensity and quality. Suggestions are given for future areas of optimization of beam filtering and collimation. PMID- 2268235 TI - Investigation of neutron beams for the realization of boron neutron capture therapy. AB - Results of the initial theoretical and experimental work performed at the Institute of Nuclear Technics of the Budapest Technical University (BTU NTI) regarding the design of a pure thermal neutron field for neutron capture therapy experiments are reported. Calculations show that a thermal neutron flux of approximately 10(9) neutrons cm-2s-1 will be generated using a filter made of graphite and bismuth. PMID- 2268236 TI - Clinical results of boron neutron capture therapy. PMID- 2268237 TI - Intermediate energy neutron beams from the MURR. AB - Several reactors in the United States are potential candidates to deliver beams of intermediate energy neutrons for NCT. At this time, moderators, as compared to filters, appear to be the more effective means of tailoring the flux of these reactors. The objective is to sufficiently reduce the flux of fast neutrons while producing enough intermediate energy neutrons for treatments. At the University of Missouri Research Reactor (MURR), the code MCNP has recently been used to calculate doses in a phantom. First, "ideal" beams of 1, 35, and 1000 eV neutrons were analyzed to determine doses and advantage depths in the phantom. Second, a high quality beam that had been designed to fit in the thermal column of the MURR, was reanalyzed. MCNP calculations of the dose in phantom in this beam confirmed previous calculations and showed that this beam would be a nearly ideal one with neutrons of the desired energy and also a high neutron current. However, installation of this beam will require a significant modification of the thermal column of the MURR. Therefore, a second beam that is less difficult to build and install, but of lower neutron current, has been designed to fit in MURR port F. This beam is designed using inexpensive A1, S, and Pb. The doses calculated in the phantom placed in this beam show that it will be satisfactory for sample tests, animal tests, and possible initial patient trials. Producing this beam will require only modest modifications of the existing tube. PMID- 2268238 TI - Progress towards boron neutron capture therapy at the High Flux Reactor Petten. AB - During 1988 the first positive steps were taken to proceed with the design and construction of a neutron capture therapy facility on the High Flux Reactor (HFR) at Petten. The immediate aim is to realise within a short time (summer 1989), an epithermal neutron beam for radiobiological and filter optimisation studies on one of the 10 small aperture horizontal beam tubes. The following summer, a much larger neutron beam, i.e., in cross section and neutron fluence rate, will be constructed on one of the two large beam tubes that replaced the old thermal column in 1984. This latter beam tube faces one whole side of the reactor vessel, extending from a 50 x 40 cm input aperture to a 35 x 35 cm exit hole. The radiotherapeutic facility will be housed here, with the intention to start clinical trials at the beginning of 1991. This paper describes the present status of the project and includes: a general description of the pertinent characteristics with respect to NCT of the HFR; results of the recently completed preliminary neutron metrology and computer modeling at the input end of the candidate beam tube; the structure and planning of the proposed Work Programme; and the respective direct and indirect participation and collaboration with the Netherlands Cancer Institute and the European Collaboration Group on BNCT. PMID- 2268240 TI - Georgia Tech Research Reactor epithermal beam. PMID- 2268239 TI - Installation and testing of an optimized epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR). AB - NCT is a binary system, in which 10B is physiologically targeted to tumor and then allowed to interact with thermal neutrons generated in the treatment volume by an externally applied neutron beam. Consequently, an unusually large number of parameters are obtained, which bear on the resultant Therapeutic Gain (TG). However, a perusal of these data, as illustrated in Figure 7, indicates that the TG would increase significantly beyond values projected in this paper if the absolute amount of 10B could be increased above 30 ppm. For example, increasing 10B concentration in tumor to 45 ppm would increase TG by approximately 33% (with a T/N of 5). A similar increase in TG would follow an increase in T/N from 5 to 10. Those associated with the development of boron compounds for NCT feel that such developments are within reach. PMID- 2268241 TI - Neutron beam design and performance for BNCT in Czechoslovakia. PMID- 2268242 TI - Clinical considerations for neutron capture therapy of brain tumors. AB - The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues. PMID- 2268243 TI - Neutron spectrum measurements in the aluminum oxide filtered beam facility at the Brookhaven Medical Research Reactor. AB - Neutron spectrum measurements were performed on the aluminum oxide filter installed in the Brookhaven Medical Research Reactor (BMRR). For these measurements, activation foils were irradiated at the exit port of the beam facility. A technique based on dominant resonances in selected activation reactions was used to measure the epithermal neutron spectrum. The fast and intermediate-energy ranges of the neutron spectrum were measured by threshold reactions and 10B-shielded 235U fission reactions. Neutron spectral data were derived from the activation data by two approaches: (1) a short analysis which yields neutron flux values at the energies of the dominant or primary resonances in the epithermal activation reactions and integral flux data for neutrons above corresponding threshold or pseudo-threshold energies, and (2) the longer analysis which utilized all the activation data in a full-spectrum, unfolding process using the FERRET spectrum adjustment code. This paper gives a brief description of the measurement techniques, analysis methods, and the results obtained. PMID- 2268244 TI - Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors. AB - Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described. PMID- 2268245 TI - Epithermal beam development at the BMRR: dosimetric evaluation. PMID- 2268246 TI - A beam-modification assembly for experimental neutron capture therapy of brain tumors. PMID- 2268248 TI - Monte Carlo methods of neutron beam design for neutron capture therapy at the MIT Research Reactor (MITR-II). AB - Monte Carlo methods of coupled neutron/photon transport are being used in the design of filtered beams for Neutron Capture Therapy (NCT). This method of beam analysis provides segregation of each individual dose component, and thereby facilitates beam optimization. The Monte Carlo method is discussed in some detail in relation to NCT epithermal beam design. Ideal neutron beams (i.e., plane-wave monoenergetic neutron beams with no primary gamma-ray contamination) have been modeled both for comparison and to establish target conditions for a practical NCT epithermal beam design. Detailed models of the 5 MWt Massachusetts Institute of Technology Research Reactor (MITR-II) together with a polyethylene head phantom have been used to characterize approximately 100 beam filter and moderator configurations. Using the Monte Carlo methodology of beam design and benchmarking/calibrating our computations with measurements, has resulted in an epithermal beam design which is useful for therapy of deep-seated brain tumors. This beam is predicted to be capable of delivering a dose of 2000 RBE-cGy (cJ/kg) to a therapeutic advantage depth of 5.7 cm in polyethylene assuming 30 micrograms/g 10B in tumor with a ten-to-one tumor-to-blood ratio, and a beam diameter of 18.4 cm. The advantage ratio (AR) is predicted to be 2.2 with a total irradiation time of approximately 80 minutes. Further optimization work on the MITR-II epithermal beams is expected to improve the available beams. PMID- 2268249 TI - Physics design for the Brookhaven Medical Research Reactor epithermal neutron source. AB - A collaborative effort by researchers at the Idaho National Engineering Laboratory and the Brookhaven National Laboratory has resulted in the design and implementation of an epithermal-neutron source at the Brookhaven Medical Research Reactor (BMRR). Large aluminum containers, filled with aluminum oxide tiles and aluminum spacers, were tailored to pre-existing compartments on the animal side of the reactor facility. A layer of cadmium was used to minimize the thermal neutron component. Additional bismuth was added to the pre-existing bismuth shield to minimize the gamma component of the beam. Lead was also added to reduce gamma streaming around the bismuth. The physics design methods are outlined in this paper. Information available to date shows close agreement between calculated and measured beam parameters. The neutron spectrum is predominantly in the intermediate energy range (0.5 eV - 10 keV). The peak flux intensity is 6.4E + 12 n/(m2.s.MW) at the center of the beam on the outer surface of the final gamma shield. The corresponding neutron current is 3.8E + 12 n/(m2.s.MW). Presently, the core operates at a maximum of 3 MW. The fast-neutron KERMA is 3.6E 15 cGy/(n/m2) and the gamma KERMA is 5.0E-16 cGY/(n/m2) for the unperturbed beam. The neutron intensity falls off rapidly with distance from the outer shield and the thermal flux realized in phantom or tissue is strongly dependent on the beam delimiter and target geometry. PMID- 2268247 TI - Tumor targeting agents for neutron capture therapy. PMID- 2268250 TI - A calculational study of tangential and radial beams in HIFAR for neutron capture therapy. AB - It is generally accepted that for biological purposes a tangential neutron beam is preferable to a radial beam because of its lower gamma and fast neutron contamination. Nevertheless radial broad spectrum epithermal neutron beams are currently being considered for boron neutron capture therapy of deep-seated tumours since they have the potential to deliver a more intense dose. A calculational study of a conceptual tangential beam and a filtered radial beam in the DIDO type reactor HIFAR was undertaken. A two-dimensional transport code was used. The tangential beam was found to be superior in therapeutic gain at depth in tissue to an aluminium fluoride (AIF3) filtered radial beam, while the dose rates of the beams were comparable. PMID- 2268251 TI - [Immunologic memory in the course of udder immunization for the protection of calves against Salmonella infections]. AB - Cows were vaccinated once or twice intracisternally in order to protect calves against salmonella infections. The amount of antibodies measured in the colostrum of re-vaccinated and not re-vaccinated cows indicated that a sensitive immunological memory has been provoked by this vaccination technique. This immunological memory showed a distinct synchronism with the state of pregnancy in order to provide a maximum amount of antibodies in the colostrum. PMID- 2268252 TI - [Serologic studies of the occurrence of Borrelia burgdorferi in domestic animals in Berlin (West)]. AB - The prevalence of B. burgdorferi, the causative agent of Lyme Borreliosis in humans, was determined in domestic animals living in Berlin. 189 dogs, 29 cats, 224 horses and 194 cows were investigated. Using the indirect immunofluorescence test (IFT) 5.8% of the dogs and 24.5% of the cows investigated showed a positive reaction at titres of 1:128 or higher. Horses and cats gave negative results. ELISA was more sensitive than IFT. 10.1% of the dogs, 16.1% of the horses and 66% of the local cows showed positive reaction. Domestic animals seem to be in contact with B. burgdorferi and can be a reservoir for the spirochete. Also there is the possibility that domestic animals get clinically ill. PMID- 2268253 TI - [Detection of verotoxin-producing E. coli (VTEC) in healthy cattle and swine with the DNA-DNA colony hybridization method]. AB - With the DNA-DNA colony hybridization technique using specific gene probes for Verotoxin 1 (VT 1) and Verotoxin 2 (VT 2) 2100 E. coli strains from healthy animals were tested. Ten out of 82 milk cows (21.2%), 20 out of 212 beef cattle (9.4%) and five out of 75 pigs (6.7%) were found to carry genes for VT 1, VT 2 or both toxins, respectively. Among these strains the biotypes 5 and 6 were predominant. Some of the serotyped isolates have been described to be pathogenic for humans, like O157:H7, 082:H8, 0116, 0113, 0126 and 091, respectively. The unexpected high incidence of VTEC positive healthy animals possibly indicates a health hazard for human beings. Further investigations on the incidence of VTEC in food are necessary. PMID- 2268254 TI - [Immunoprophylaxis against an acute P. multocida type D infection in Cairina moschata]. AB - An acute P. multocida infection led to severe losses in a big Cairina moschata fattening farm. All isolated strains belong to serogroup D. After testing the virulence and immunogenic properties of the isolated strains in NMRI mice, we used an highly virulent and immunogenic strain for developing an inactivated vaccine (formaline inactivated, Al (OH)3 adsorbed, with a content of 3 x 10(9) bacteria/ml). Two sc. immunizations of Cairina at an age of 10 and 24 days resulted in immunity. All immunized animals survived the challenge infection. The immunity was stable till the 8th week after the 2nd immunization, later the intensity of the immunity decreased. A threefold immunization procedure in the Cairina farm was very successful. PMID- 2268255 TI - [Comments on computer programs and their use as educational aids for veterinary practice]. AB - Comparisons to older educational methods are drawn. Common aspects of computer supported programs and their handling at training and development for the practice are being discussed. Different problems of new methods of informatics are shown. PMID- 2268256 TI - Polymorphism of histone H1 in goose erythrocytes. PMID- 2268257 TI - Nucleosome unit repeat size in aneuploid mice. AB - Male 8-day-old mice that have part of chromosome 7 translocated to an X chromosome [T(X;7)1 Ct] and that are chromosomally unbalanced for chromosome 7, and consequently trisomic for that part of chromosome 7, were found to have a smaller nucleosome repeat unit size than normal littermate males (Rake, A. V., and Edwards, R. H., Biochem. Genet. 25:671, 1987). This smaller nucleosome size is maintained in adult trisomic males. Males with a balanced chromosomal translocation [T(X;7)1Ct] had a normal nucleosome size compared to their littermates. The nucleosome unit size is not altered in two other types of aneuploid mice studied (XO vs XX, 2n = 39 and 40, respectively; and Ts12(17) vs normal, 2n = 40 and 41, respectively). PMID- 2268258 TI - Vitellogenin protein diversity in the Hawaiian Drosophila. AB - Egg and female hemolymph proteins were resolved via SDS-polyacrylamide gel electrophoresis in a diverse array of 33 endemic Hawaiian drosophilids, encompassing 17 picture-winged species, 3 of the antopocerus species group, 9 fungus feeders, 1 species from each of the modified mouthparts, crassifemur and ciliated tarsus groups, and 1 Scaptomyza species. Molecular weights of the two (10 species) or three vitellogenin bands (22 species) were highly variable, spanning a 7-kD range. The largest vitellogenin, V1, was the most variable, showing a change of some 10% in its mean size of 47.6 kD. The smallest V3 vitellogenin, mean size 44.1 kD, was evolutionarily the most conservative in size. The species Drosophila hawaiiensis was found to be polymorphic for two/three vitellogenin bands and, also, polymorphic with respect to the size of the V1 protein. No inter- or intrapopulation variability in vitellogenin size was detected in 10 other species examined. The major features of vitellogenin protein evolution in the Hawaiian Drosophila are change in molecular weight and regulatory differences that result in quantitative differences between species in patterns of vitellogenin protein production. PMID- 2268259 TI - Biochemical analysis of related, independently arising histocompatibility mutants: bm17 and KB-98 enlarge the "bg series" of H-2Kb mutants. AB - The "bg" series of MHC mutations is the most prevalent type of mutations of Kb in C57BL/6 mice screened by reciprocal tail skin grafting. The basis for identification of this series of mutations is the incompatibility of grafts between the parental B6 and the mutant. This series takes the longest to reciprocally reject the skin grafts. The series can be subdivided into "bg 1" and "bg 2" groups based on Kb-restricted recognition of virus-infected mutant target cells. The biochemical basis for these mutations are amino acid substitutions at residues 116 and 121 of the Kb transplantation antigen. These substitutions do not alter monoclonal antibody binding sites. The structural basis of MAb binding and the genetic basis of the mutation are discussed. PMID- 2268260 TI - Stoichiometry and stability of caldesmon in native thin filaments from sheep aorta smooth muscle. AB - Ca2(+)-regulated native thin filaments were extracted from sheep aorta smooth muscle. The caldesmon content determined by quantitative gel electrophoresis was 0.06 caldesmon molecule/actin monomer (1 caldesmon molecule per 16.3 actin monomers). Dissociation of caldesmon and tropomyosin from the thin filament and the depolymerization of actin was measured by sedimenting diluted thin filaments. Actin critical concentration was 0.05 microM at 10.1 and 0.13 at 10.05 compared with 0.5 microM for pure F-actin. Tropomyosin was tightly bound, with half maximal dissociation at less than 0.3 microM thin filaments (actin monomer) under all conditions. Caldesmon dissociation was independent of tropomyosin and not co operative. The concentration of thin filaments where 50% of the caldesmon was dissociated (CD50) ranged from 0.2 microM (actin monomer) at 10.03 to 8 microM at 10.16 in a 5 mM-MgCl2, pH 7.1, buffer. Mg2+, 25 mM at constant I, increased CD50 4-fold. CD50 was 4-fold greater at 10(-4) M-Ca2+ than at 10(-9) M-Ca2+. Aorta heavy meromyosin (HMM).ADP.Pi complex (2.5 microM excess over thin filaments) strongly antagonized caldesmon dissociation, but skeletal-muscle HMM.ADP.Pi did not. The behaviour of caldesmon in native thin filaments was indistinguishable from caldesmon in reconstituted synthetic thin filaments. The variability of Ca2(+)-sensitivity with conditions observed in thin filament preparations was shown to be related to dissociation of regulatory caldesmon from the thin filament. PMID- 2268261 TI - Effects of hyperthyroidism and hypothyroidism on glutamine metabolism by skeletal muscle of the rat. AB - 1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions. PMID- 2268262 TI - Neutral-sugar transport by rat liver lysosomes. AB - Transport of D-glucose was studied in Percoll-gradient-purified rat liver lysosomes. D-Glucose uptake had a Km of 22 mM and a t1/2 of approx. 30 s. D Fucose, 2-deoxyglucose and methyl alpha-glucoside were the most effective competitors for uptake of D-glucose, although D-galactose, D-mannose, D-xylose and L-fucose also appeared to compete for uptake. L-Glucose was a poor competitor for uptake. No competition was observed with N-acetyl-D-glucosamine, N-acetyl-D galactosamine, D-glucuronic acid, N-acetylneuraminic acid, D-glucosamine or the amino acids L-glycine, L-lysine and L-proline. Uptake was unaffected by N ethylmaleimide, dithiothreitol, KCl, NaCl, ATP/Mg or alteration of buffer pH. D Glucose efflux from lysosomes was temperature-dependent, with a Q10 of 2.3, and was inhibited by cytochalasin B. Counter-transport could not be demonstrated. In contrast, L-fucose uptake had a Km of 65 mM and was largely unaffected by 5 M excess of neutral D-sugars. Both uptake and efflux of L-fucose were inhibited by cytochalasin B. It appears that lysosomes possess a facilitated transport system for D-glucose and perhaps other neutral D-sugars that is discrete from transport systems for acetylated and acidic sugars. PMID- 2268263 TI - Detection of inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase by thioinosinic acid and azathioprine by a new colorimetric assay. AB - The colorimetric assay for 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase (phosphoribosylamino-imidazolecarboxamide formyltransferase; EC 2.1.2.3) has been extensively modified. The modified assay is based upon the short-term permanganate oxidation of the folate product, tetrahydrofolate (H4folate) to p-aminobenzoyl glutamate (pABG). The modified assay was used to detect the transformylase activity in crude extracts of peripheral-blood mononuclear cells (PBMCs). Azathioprine and its metabolite, thioinosinic acid (tIMP), are competitive inhibitors (with respect to AICAR) of the chicken liver transformylase and the transformylase from PBMCs of the MRL/lpr mouse, an animal model of systemic autoimmune disease. The Ki values of tIMP and azathioprine for the chicken liver enzyme are 39 +/- 4 microM and 120 +/- 10 microM, whereas the Ki values for the enzyme from PBMCs of the MRL/lpr mouse are 110 +/- 20 microM and 90 +/- 14 microM respectively. The anti-inflammatory drugs ibuprofen and naproxen are also inhibitors of the transformylase. PMID- 2268264 TI - Molecular-mass heterogeneity of Griffonia simplicifolia lectin IV subunits. Differences in the oligosaccharide moieties in the N-terminal region. AB - Lectin IV of Griffonia simplicifolia (Mr approximately 56,000), which has a strong affinity for both the Lewis b and Y blood-group determinants, is a dimeric protein of two subunits, alpha (29 kDa) and beta (27 kDa), separable by SDS/PAGE and containing covalently linked oligosaccharide. After digestion with N glycanase, the protein migrates as a single band with a mobility identical with that of the beta-subunit. After cleavage with hydroxylamine of 3H-labelled, but otherwise intact, lectin, the radioactively labelled oligosaccharide was found to be associated with two blocked N-terminal peptides separable by h.p.l.c. and having identical amino acid compositions. One of these had three or four glucosamine residues per molecule, whereas the other had only one or two. Sequence analyses of these, as well as of a 21 kDa hydroxylamine-cleaved fragment and of the intact lectin pretreated with pyroglutamate aminopeptidase, have provided a unique sequence for residues 1-62 of the two subunits. Evidence is presented for two sites of N-linked oligosaccharide attachment at Asn-5 and Asn 18. Whereas the alpha-subunit has oligosaccharide linked to both sites, the beta subunit has carbohydrate associated with only one (Asn-18). Sugar analyses of the whole lectin reveal a monosaccharide composition of (Xyl)3(Fuc)2(Man)10(GlcNAc)6, representing 6.4% of the mass of the molecule. Taken together with the susceptibility of the Asn-5 linkage (but not of Asn-18) to N-glycanase digestion, the observations indicate that the structures of the oligosaccharides at residues 5 and 18 are different. PMID- 2268265 TI - Chemical modification of aldehyde dehydrogenase by a vinyl ketone analogue of an insect pheromone. AB - A major component of the sex pheromone from the tobacco budworm moth Heliothis virescens is a C16 straight-chain aldehyde with a single unsaturation at the eleventh position. The sex pheromones are inactivated when metabolized to their corresponding acids by insect aldehyde dehydrogenase. During this investigation it was demonstrated that the C16 aldehyde is a good substrate for human aldehyde dehydrogenase (EC 1.2.1.3) isoenzymes E1 and E2 with Km and Kcat. values at pH 7.0 of 2 microM and 0.4 mumol of NADH/min per mg and of 0.6 microM and 0.24 mumol of NADH/min per mg respectively. A vinyl ketone analogue of the pheromone inhibited insect pheromone metabolism; it also inactivated human aldehyde dehydrogenase. Total inactivation of both isoenzymes was achieved at stoichiometric (equal or less than the subunit number) concentrations of vinyl ketone, incorporating 2.1-2.6 molecules/molecule of enzyme. Substrate protection was observed in the presence of the parent aldehyde and 5'-AMP. Peptide maps of tryptic digests of the E2 isoenzyme modified with 3H-labelled vinyl ketone showed that incorporation occurred into a single peptide peak. The labelled peptide of E2 isoenzyme was further purified on h.p.l.c. and sequenced. The label was incorporated into cysteine-302 in the primary structure of E2 isoenzyme, thus indicating that cysteine-302 is located in the aldehyde substrate area of the active site of aldehyde dehydrogenase. Affinity labelling of aldehyde dehydrogenase with vinyl ketones may prove to be of general utility in biochemical studies of these enzymes. PMID- 2268266 TI - Isocitrate lyase from Phycomyces blakesleeanus. The role of Mg2+ ions, kinetics and evidence for two classes of modifiable thiol groups. AB - Isocitrate lyase was purified from Phycomyces blakesleeanus N.R.R.L. 1555(-). The native enzyme has an Mr of 240,000. The enzyme appeared to be a tetramer with apparently identical subunits of Mr 62,000. The enzyme requires Mg2+ for activity, and the data suggest that the Mg2(+)-isocitrate complex is the true substrate and that Mg2+ ions act as a non-essential activator. The kinetic mechanism of the enzyme was investigated by using product and dead-end inhibitors of the cleavage and condensation reactions. The data indicated an ordered Uni Bi mechanism and the kinetic constants of the model were calculated. The spectrophotometric titration of thiol groups in Phycomyces isocitrate lyase with 5.5'-dithiobis-(2-nitrobenzoic acid) gave two free thiol groups per subunit of enzyme in the native state and three in the denatured state. The isocitrate lyase was completely inactivated by iodoacetate, with non-linear kinetics. The inactivation data suggest that the enzyme has two classes of modifiable thiol groups. The results are also in accord with the formation of a non-covalent enzyme-inhibitor complex before irreversible modification of the enzyme. Both the equilibrium constants for formation of the complex and the first-order rate constants for the irreversible modification step were determined. The partial protective effect of isocitrate and Mg2+ against iodoacetate inactivation was investigated in a preliminary form. PMID- 2268267 TI - Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells. AB - Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin. PMID- 2268268 TI - Activation of factor V during intrinsic and extrinsic coagulation. Inhibition by heparin, hirudin and D-Phe-Pro-Arg-Ch2Cl. AB - The validity of the hypothesis that Factor Xa activates Factor V in heparinized plasma was examined by establishing the temporal relationships between Factor V proteolysis and prothrombin consumption in plasma. Factor V was cleaved into Factor Va heavy chain (approx. 110 kDa) and an intermediate (approx. 230 kDa) 30 s after CaCl2 was added to contact-activated plasma (CAP). The larger fragment was converted into Factor V activation peptide (approx. 150 kDa) and Factor Va light chain (approx. 80 kDa) 15 s later. Heparin (approx. 0.05 microM) delayed Factor V proteolysis in CAP by at least 30 s. On supplementing CAP with 1 nM Factor Xa or 1 nM-thrombin, Factor V was activated 15 s later. Heparin prolonged by 15 s and 45 s the time required to demonstrate Factor V activation in CAP supplemented with Factor Xa and thrombin respectively. Factor V was activated 20 s after tissue factor and CaCl2 were added to plasma, both in the absence and in the presence of approx. 0.05 microM-heparin. In contrast, hirudin and D-Phe-Pro Arg-CH2Cl (two thrombin inhibitors more effective than heparin) delayed Factor V activation in this plasma by at least 30 s. The fragments of Factor V obtained in heparinized CAP suggest thrombin escapes inhibition and contributes to Factor V activation in that plasma. Production of Factor Va heavy chain and the 230 kDa Factor V fragment invariably preceded efficient prothrombin activation. These observations suggest that heparin, hirudin and D-Phe-Pro-Arg-CH2Cl delay Factor V activation by inhibiting thrombin. The availability of Factor Xa markedly moderates the ability of heparin to inhibit Factor V activation. PMID- 2268269 TI - Role of lysosomal and cytosolic pH in the regulation of macrophage lysosomal enzyme secretion. AB - Rapid and parallel secretion of lysosomal beta-N-acetylglucosaminidase and preloaded fluorescein-labelled dextran was initiated in macrophages by agents affecting intracellular pH (methylamine, chlorpromazine, and the ionophores monensin and nigericin). In order to evaluate the relative role of changes in lysosomal and cytosolic pH, these parameters were monitored by using pH-sensitive fluorescent probes [fluorescein-labelled dextran or 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein]. All agents except chlorpromazine caused large increases in lysosomal pH under conditions where they induced secretion. By varying extracellular pH and ion composition, the changes in lysosomal and cytosolic pH could be dissociated. Secretion was then found to be significantly modulated by changes in cytosolic pH, being enhanced by alkalinization and severely inhibited by cytosolic acidification. However, changes in cytosolic pH in the absence of stimulus were unable to initiate secretion. Dissociation of the effects on lysosomal and cytosolic pH was also achieved by combining stimuli with either nigericin or acetate. Further support for a role of intracellular pH in the control of lysosomal enzyme secretion was provided by experiments where bicarbonate was included in the medium. The present study demonstrates that an increase in lysosomal pH is sufficient to initiate lysosomal enzyme secretion in macrophages and provides evidence for a significant regulatory role of cytosolic pH. PMID- 2268270 TI - Sensitivity of inhibition of rat liver mitochondrial outer-membrane carnitine palmitoyltransferase by malonyl-CoA to chemical- and temperature-induced changes in membrane fluidity. AB - We have tested the possibility that alterations in the fluidity of the outer membrane of rat liver mitochondria could result in changes in the sensitivity of overt carnitine palmitoyltransferase (CPT I) to malonyl-CoA [Zammit (1986) Biochem. Soc. Trans. 14. 676-679]. The sensitivity of CPT I to malonyl-CoA inhibition was measured by using highly purified mitochondrial outer membranes prepared from fed or 48 h-starved rats in the presence and absence of agents that increase membrane fluidity by perturbing membrane lipid order [benzyl alcohol, isoamyl alcohol (3-methylbutan-l-ol) and 2-(2-methoxyethoxy)ethyl-8-(cis-2-n octylpropyl)octanoate (A2C)]. All these agents resulted in marked decreases in the ability of malonyl-CoA to inhibit CPT I. This effect was accompanied by a modest increase in the absolute activity of CPT I in the absence of malonyl-CoA when the short-chain alcohols were used, but not when A2C was used, suggesting that the effect of increased membrane fluidity to decrease the malonyl-CoA sensitivity of CPT I may occur independently from other actions that may affect more directly the active site of the enzyme. In confirmation of the potential importance of fluidity changes, we showed that a marked increase in sensitivity of CPT I to malonyl-CoA could be produced when assays were performed at lower temperatures than those normally employed. These observations are discussed in the context of the slowness of the changes in CPT I sensitivity to malonyl-CoA inhibition that are induced by physiological perturbations. PMID- 2268271 TI - Effect of lovastatin on acyl-CoA: cholesterol O-acyltransferase (ACAT) activity and the basolateral-membrane secretion of newly synthesized lipids by CaCo-2 cells. AB - Lovastatin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase activity, was used to study the regulation of cholesterol metabolism and the basolateral-membrane secretion of triacylglycerol and cholesterol in the human intestinal cell line CaCo-2. At 0.1 microgram/ml, lovastatin decreased 3H2O incorporation into cholesterol by 71%. In membranes prepared from cells incubated with lovastatin for 18 h, HMG-CoA reductase activity was induced 4-8-fold. Mevalonolactone prevented this induction. In intact cells, lovastatin (10 micrograms/ml) decreased cholesterol esterification by 50%. The reductase inhibitor decreased membrane acyl-CoA:cholesterol O acyltransferase (ACAT) activity by 50% at 5 micrograms/ml. ACAT inhibition by lavastatin was not reversed by adding excess of cholesterol or fatty acyl-CoA to the assay. Lovastatin, in the presence or absence of mevalonolactone, decreased the basolateral secretion of newly synthesized cholesteryl esters and triacylglycerols. Lovastatin also inhibited the esterification of absorbed cholesterol and the secretion of this newly synthesized cholesteryl ester. Lovastatin is a potent inhibitor of cholesterol synthesis in CaCo-2 cells. Moreover, it is a direct inhibitor of ACAT activity, independently of its effect on HMG-CoA reductase and cholesterol synthesis. PMID- 2268272 TI - Lactate production is the major metabolic fate of glucose in splenocytes and is altered in spontaneously diabetic BB rats. AB - Enhanced glucose metabolism is necessary to support the activation and proliferation of lymphocytes. To define further quantitatively the metabolic fates of glucose and assess glucose utilization both in normal cells and in an autoimmune disease with abnormal lymphocytes, [U-14C]glucose conversion into 14CO2 and the production of lactate and pyruvate were measured in splenocytes. Cells from non-diabetes-prone (BBn) and spontaneously diabetic (BBd) rats were studied both freshly isolated 'resting' and cultured for 96 h with and without concanavalin A (Con A) stimulation. (1) Lactate was confirmed to be the major end product in both freshly isolated (53% of utilized glucose) and unstimulated cultured (62% of utilized glucose) cells from BBn animals studied at (2-8) x 10(6) cells/ml concentration. The use of concentrations from 10 x 10(6) to 300 x 10(6) cells/ml resulted in progressively less lactate production per 10(6) splenocytes. (2) Cells from BBd animals after stimulation with Con A incorporated less [3H]thymidine and produced significantly less lactate (155 +/- 14 versus 305 +/- 24 nmol/2 h per 10(6) cells) than did BBn cells (P less than 0.05). (3) However, more lactate (101 +/- 8 versus 78 +/- 6 nmol/5 h per 10(6) cells) was produced by 'resting' cells from BBd animals compared with BBn (P less than 0.03), and this difference was sustained after 4 days in culture. (4) Significantly greater amounts of pyruvate were produced by BBd than by BBn cells, particularly when stimulated with Con A, suggesting an alteration in the availability of reducing equivalents in BBd cells. (5) These results are consistent with prior metabolic as well as immunological 'activation' of cells in vivo in the BB diabetic animals. PMID- 2268273 TI - Propeptide recognition by the vitamin K-dependent carboxylase in early processing of prothrombin and factor X. AB - Precursors of vitamin K-dependent proteins are synthesized with a propeptide that is believed to target these proteins for gamma-carboxylation by the vitamin K dependent carboxylase. In this study synthetic propeptides were used to investigate gamma-carboxylation of the prothrombin and factor X precursors in rat liver microsomes. The extent of prothrombin processing by the carboxylase was also investigated. Antisera raised against the human prothrombin and factor X propeptides only recognized precursors with the respective propeptide regions. The data demonstrate structural differences in the propeptide region of the prothrombin and the factor X carboxylase substrates which raises questions about the hypothesis of a common propeptide binding site on the carboxylase for all precursors of vitamin K-dependent proteins. The hypothesis of separate binding sites is supported by data which demonstrate differences in binding of the prothrombin and factor X precursors to membrane fragments from rough and smooth microsomes. gamma-Carboxylation of the prothrombin precursors in vitro was investigated with conformational specific antibodies raised against a portion of the Gla (gamma-carboxyglutamic acid) region extending from residue 15 to 24. The synthetic peptide used as antigen contains three of the ten potential Gla sites in prothrombin. It is shown that these antibodies do not recognize mature prothrombin but recognize the decarboxylated protein. It is also demonstrated that the epitope is Ca2(+)-dependent. The antibodies were used to assess gamma carboxylation of the prothrombin precursor in membrane fragments from microsomal membranes. The results suggest that microsomal gamma-carboxylation does not involve Glu residues 16, 19 and 20 of the Gla region. PMID- 2268274 TI - Chemical modification of rat liver microsomal glutathione transferase defines residues of importance for catalytic function. AB - Amino acid residues that are essential for the activity of rat liver microsomal glutathione transferase have been identified using chemical modification with various group-selective reagents. The enzyme reconstituted into phosphatidylcholine liposomes does not require stabilization with glutathione for activity (in contrast with the purified enzyme in detergent) and can thus be used for modification of active-site residues. Protection by the product analogue and inhibitor S-hexylglutathione was used as a criterion for specificity. It was shown that the histidine-selective reagent diethylpyrocarbonate inactivated the enzyme and that S-hexylglutathione partially protected against this inactivation. All three histidine residues in microsomal glutathione transferase could be modified, albeit at different rates. Inactivation of 90% of enzyme activity was achieved within the time period required for modification of the most reactive histidine, indicating the functional importance of this residue in catalysis. The arginine-selective reagents phenylglyoxal and 2,3-butanedione inhibited the enzyme, but the latter with very low efficiency; therefore no definitive assignment of arginine as essential for the activity of microsomal glutathione transferase can be made. The amino-group-selective reagents 2,4,6 trinitrobenzenesulphonate and pyridoxal 5'-phosphate inactivated the enzyme. Thus histidine residues and amino groups are suggested to be present in the active site of the microsomal glutathione transferase. PMID- 2268275 TI - Expression and routeing of human lysosomal alpha-glucosidase in transiently transfected mammalian cells. AB - Previously isolated lysosomal alpha-glucosidase cDNA clones were ligated to full length constructs for expression in vitro and in mammalian cells. One of these constructs (pSHAG1) did not code for functional enzyme, due to an arginine residue instead of a tryptophan residue at amino acid position 402. The mutation does not affect the rate of enzyme synthesis, but interferes with post translational modification and intracellular transport of the acid alpha glucosidase precursor. Using immunocytochemistry it is demonstrated that the mutant precursor traverses the endoplasmic reticulum and the Golgi complex, but does not reach the lysosomes. Pulse-chase experiments suggest premature degradation. The Trp-402-containing enzyme (encoded by construct pSHAG2) is processed properly, and has catalytic activity. A fraction of the enzyme is localized at the plasma membrane. It is hypothesized that membrane association of the acid alpha-glucosidase precursor, as demonstrated by Triton X-114 phase separation, is responsible for transport to this location. Transiently expressed acid alpha-glucosidase also enters the secretory pathway, since a catalytically active precursor is found in the culture medium. This precursor has the appropriate characteristics for use in enzyme replacement therapy. Efficient uptake via the mannose 6-phosphate receptor results in degradation of lysosomal glycogen in cultured fibroblasts and muscle cells from patients with glycogenosis type II. PMID- 2268277 TI - Elimination of a reactive thiol group from the active site of chloramphenicol acetyltransferase. AB - 1. The type III variant of chloramphenicol acetyltransferase (CATIII) is resistant to inactivation by ionizable modifying reagents such as 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) and iodoacetate, whereas it is sensitive to inhibition by similar but uncharged reagents, including 4,4'-dithiodipyridine, methyl methanethiolsulphonate (MMTS) and iodoacetamide. The target for these thiol-modifying reagents has been postulated to be Cys-31. This residue is situated within a part of the chloramphenicol-binding site formed largely from the side chains of hydrophobic amino acid residues, which might be expected to discriminate against the access of ionized ligands to Cys-31. 2. The substitution of Cys-31 by alanine, serine, threonine or methionine yields an enzyme that is resistant to inactivation by thiol-specific reagents. Replacement of Cys-31 by alanine, serine or threonine results in increased Km values for chloramphenicol with only small changes in kcat.. In contrast, the Cys-31----Met substitution mainly affects kcat. values. Although the kcat. for chloramphenicol acetylation is decreased 13-fold compared with wild-type CAT, the kcat. for the acetyl-CoA hydrolysis reaction, which occurs in the absence of chloramphenicol, is increased 2.7-fold. 3. MMTS modification of cysteine residues results in an adduct (-CH2-S S-CH3) that is structurally similar to the side chain of a methionine residue ( CH2-CH2-S-CH3). The kinetic properties of MMTS-modified CATIII closely resemble those of [Met31]CAT. PMID- 2268276 TI - Characterization of the human lysosomal alpha-glucosidase gene. AB - The gene coding for human lysosomal alpha-glucosidase was cloned and its structure was determined. The gene is approx. 20 kb long, and contains 20 exons. The first exon is non-coding. The coding sequence of the putative catalytic site domain is interrupted in the middle by an intron of 101 bp. This intron is not conserved in the highly similar region of the human and rabbit isomaltase genes. The promoter region was defined by a CAT assay and the start of the mRNA was determined by primer extension. The promoter has features characteristic of a 'housekeeping' gene. The GC content is high (80%) and distinct TATA and CCAAT motifs are lacking. Two potential binding sites for the AP-2 transcription factor are present. Four potential Sp-1 binding sites are located downstream of the 5' end of the mRNA. PMID- 2268278 TI - Nucleotide sequences of genes encoding the type II chloramphenicol acetyltransferases of Escherichia coli and Haemophilus influenzae, which are sensitive to inhibition by thiol-reactive reagents. AB - Sensitivity of enzymes to inhibition by thiol-reactive reagents is often presented as evidence for the possible involvement of cysteine residues in substrate binding and catalysis or to highlight possible important differences in structure and mechanism between closely related enzymes. The primary phenotypic distinction between the enterobacterial type II chloramphenicol acetyltransferase (CATII; typified by the enzyme encoded by the incW transmissible plasmid pSa) and the CATI and CATIII variants is the greatly enhanced susceptibility of CATII to inactivation by thiol-specific modifying reagents. Determination of the nucleotide sequence of the gene, catII, present on pSa and that of a related determinant, catIIH, isolated from Haemophilus influenzae indicates that sensitivity to such reagents cannot be due to the presence of additional reactive cysteine residues in CATII. Comparative analysis of the inactivation of CATII and CATIII by 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), 4,4'-dithiodipyridine (DTDP) and methyl methanethiosulphonate (MMTS) suggests that (i) inactivation occurs as a result of chemical modification of the same residue (Cys-31) in each enzyme, (ii) reagents that inactivate via a pseudo-first-order process (DTNB and DTDP) appear to bind with a greater affinity to CATII, and (iii) the intrinsic reactivity of Cys-31 in CATII greatly exceeds that of the corresponding residue in CATIII. The results lead to the conclusion that a striking difference in chemical reactivity of a unique and conserved thiol group between closely related enzyme variants may not be easily explained even when a high-resolution tertiary structure is available for one of them. Plausible explanations include more favourable access of reagents to Cys-31 in CATII or an enhanced reactivity of its thiol group imposed by the side chains of residues that are not in immediate contact with it. PMID- 2268279 TI - A requirement for Zn2+ for the induction of thymidine kinase but not ornithine decarboxylase in 3T3 cells stimulated from quiescence. AB - In 3T3 cells stimulated from quiescence by serum, impaired thymidine incorporation caused by inadequate supply of Zn2+ was associated with both decreased thymidine kinase activity and a comparable decrease in its mRNA concentration. In contrast, the amount of mRNA for ribosomal protein S6 was not affected, nor was the earlier increase in the activity of ornithine decarboxylase. PMID- 2268280 TI - Structures of the asparagine-linked oligosaccharides of guinea-pig factor B of the alternative complement pathway. AB - This paper describes the structures of the asparagine-linked oligosaccharides of two forms of guinea-pig Factor B of the alternative complement pathway with different Mr values. Oligosaccharides were quantitatively liberated from both glycoproteins by hydrazinolysis, fractionated by paper electrophoresis and Bio Gel P-4 column chromatography, and their structures determined by sequential exoglycosidase digestions in conjunction with methylation analysis. Both glycoproteins were shown to have the same biantennary complex-type oligosaccharides but it is suggested that they contain different numbers of oligosaccharide chains. PMID- 2268282 TI - Induction of carcinoembryonic-antigen-gene expression in human colorectal carcinoma by sodium butyrate. AB - The effect of sodium butyrate on the expression of the carcinoembryonic-antigen (CEA) gene was studied in two poorly differentiated colorectal-carcinoma cell lines (Clone-A and MIP-101) and in one well-differentiated cell line (LS-174T); A.T.C.C. no. CCL 188). Northern-blot and dot-blot analyses indicated a steady increase in CEA mRNA from day 4 to a maximal level by day 14 after these cells were exposed to 2 mM-sodium butyrate. Studies using nuclear run-off assays followed by dot-blot hybridization to a partial CEA cDNA clone demonstrated that specific increases in gene transcription rates (3-fold in MIP-101, 4-fold in LS 174T and 6-fold in Clone-A) are not sufficient to account for the observed increases in CEA mRNA abundance. Further studies showed that CEA-specific transcripts have a half-life of about 60-80 min, and treatment with sodium butyrate increased the stability of CEA-specific transcripts to about 340 min in LS-174T cells and to about 500 min in Clone-A cells. We conclude that the induction of the CEA-gene expression by sodium butyrate in colorectal-cancer cells is mediated by both transcriptional and post-transcriptional mechanisms, with CEA mRNA stability as one of the major check-points. PMID- 2268281 TI - Hepatic iodothyronine 5'-deiodinase. The role of selenium. AB - Selenium (Se) deficiency decreased by 8-fold the activity of type 1 iodothyronine 5'-deiodinase (ID-I) in hepatic microsomal fractions from rats. Solubilized hepatic microsomes from rats injected with 75Se-labelled Na2SeO3 4 days before killing were found by chromatography on agarose gels to contain a 75Se-containing fraction with ID-I activity. PAGE of this fraction under reducing conditions, followed by autoradiography, revealed a single 75Se-containing protein (Mr 27,400 +/- 300). This protein could also be labelled with 125I-bromoacetyl reverse tri iodothyronine, an affinity label for ID-I. The results suggest that hepatic ID-I is a selenoprotein or has an Se-containing subunit essential for activity. PMID- 2268283 TI - Spectroscopic, thermodynamic and kinetic properties of Candida nitratophila nitrate reductase. AB - Visible spectra of oxidized and reduced Candida nitratophila assimilatory NAD(P)H:nitrate reductase yielded absorbance maxima of 413 nm and 423 nm, and 525 nm and 555 nm respectively, characteristic of a b5-type cytochrome. E.p.r. spectra of the partially reduced enzyme revealed a single Mo(V) species (g1 = 1.9957, g2 = 1.9664 and g3 = 1.9658) exhibiting superhyperfine coupling to a single proton [A(1H)av. = 1.4 mT]. Oxidation-reduction midpoint potentials (E'0) (25 degrees C, pH 7) for the haem and Mo-pterin prosthetic groups were determined by visible and e.p.r. potentiometric titrations and yielded values of E'0 = -174 mV (n = 1) for the haem and E'0 = -3 mV and E'0 = -27 mV for the Mo(VI)/Mo(V) and Mo(V)/Mo(IV) couples respectively. Comparison of initial rates of the NADH oxidizing and nitrate-reducing partial activities at various ionic strengths indicated electron transfer from reduced haem to Mo was rate-limiting during turnover. These results suggest a close similarity between Candida nitratophila and Chlorella vulgaris nitrate reductases. PMID- 2268284 TI - MgATP-dependent accumulation of calcium ions and inorganic phosphate in a liver reticular pool. AB - 1. MgATP-dependent Ca2+ uptake by rat liver microsomal preparations and permeabilized hepatocytes was measured in the presence or absence of Pi. 2. Monitoring of free Ca2+ in incubation systems with a Ca2+ electrode in the presence of Pi (2-7 mM) revealed a biphasic Ca2+ uptake, with the onset of a second, Pi-dependent, Ca2+ accumulation. 3. Increasing Pi concentrations (up to 10 mM) caused a progressive enlargement of 45Ca2(+)-loading capacity of microsomal fractions. 4. As a result of Pi stimulation of active Ca2+ uptake, [32P]Pi and 45Ca2+ were co-accumulated. 5. Experiments with permeabilized hepatocytes revealed that the amount of Ca2+ releasable by myo-inositol 1,4,5 trisphosphate is unaffected by Pi. PMID- 2268285 TI - Insulin-dependent contractility of glomerular mesangial cells in response to angiotensin II, platelet-activating factor and endothelin is attenuated by prostaglandin E2. AB - Culture of glomerular mesangial cells in the absence of insulin decreased the degree of contraction of individual cells in response to vasoconstrictive agonists, angiotensin II, platelet-activating factor and endothelin 1, as compared with cells cultured in the presence of insulin (0.7 nM). This change was associated with a decreased sensitivity of the intracellular Ca2+ response to vasoactive agents in fura-2-loaded cells and with an increase in the basal level of prostanoid [prostaglandins (PG) E1 and E2] production estimated by radioimmunoassay. Addition of exogenous PGE2 to insulin-exposed cells decreased the contractile response to that observed in insulin-deficient cells. Inclusion of 8-bromo cyclic AMP had a similar effect. In 45Ca2(+)-release studies it was shown that, in saponin-permeabilized insulin-exposed cells, preincubation with exogenous PGE2 or 8-bromo cyclic AMP decreased the sensitivity of 45Ca2+ release in response to Ins(1,4,5)P3, as demonstrated by an increase in the EC50 (concn. giving half-maximal effect) to 0.182 +/- 0.024 microM and 0.457 +/- 0.031 microM respectively, as compared with untreated permeabilized cells (EC50 0.091 +/- 0.021 microM). A similar decrease in Ins(1,4,5)P3-sensitive 45Ca2+ release was seen in permeabilized cells from insulin-free conditions of culture (EC50 0.20 +/ 0.061 microM). As altered glomerular haemodynamics are found in insulinopaenic diabetic conditions, it is proposed that a decrease in intracellular Ca2+ availability in response to vasoactive agonists and consequent decrease in mesangial-cell contractility contributes to the hyperfiltration seen in this condition. PMID- 2268286 TI - Storage, mobilization and secretion of cytosolic triacylglycerol in hepatocyte cultures. The role of insulin. AB - Cytosolic triacylglycerol labelled from [3H]oleate accounted for almost 50% (57 +/- 22 nmol/mg of protein) of the total cellular triacylglycerol which was newly synthesized by cultured hepatocytes during a 24 h incubation. Insulin decreased the export of triacylglycerol as very-low-density lipoprotein (VLDL) during this period. This resulted in a sequestration of newly synthesized triacylglycerol in the cytosol, rather than in the particulate fraction of the cell. Longer periods of incubation with [3H]oleate resulted in increased concentrations of newly synthesized triacylglycerol within the cell, most of which (78 +/- 3% after 48 h; 80 +/- 3% after 72 h) was located within the cytosolic fraction. The quantity of newly synthesized triacylglycerol in the cell cytosol was further increased by insulin. During these periods there were decreases in the amounts of triacylglycerol associated with the particulate fraction of the cell, irrespective of the presence or absence of insulin. In no case was a decrease in VLDL triacylglycerol secretion in response to insulin accompanied by an increased triacylglycerol content in the particulate fraction of the cell. In some experiments, the fate of the cytosolic triacylglycerol was studied by pulse labelling with [3H]oleate. In these cases, when insulin was removed from the medium of cells to which they had previously been exposed, more newly synthesized triacylglycerol was secreted compared with cells which had not been exposed to insulin. This extra triacylglycerol was mobilized from the cytosolic rather than from the particulate fraction of the cell. Subsequent addition of insulin to the medium prevented the mobilization of cytosolic triacylglycerol. These results suggest that insulin enhances the storage of hepatocellular triacylglycerol in a cytosolic pool. Deficiency of insulin in the medium stimulates the mobilization of this pool which is channelled into the secretory pathway, entering the extracellular medium as VLDL. PMID- 2268287 TI - Lysocardiolipin formation and reacylation in isolated rat liver mitochondria. AB - Liver mitochondrial cardiolipin (CL) is distinguished from other phospholipids by the presence of linoleoyl in almost all molecular species, and the biosynthesis of these species is not yet understood. The present study was carried out in order to test the hypothesis that the linoleoyl proportion of CL may be specifically enriched by a deacylation-reacylation cycle. Incorporation of [14C]glycerol 3-phosphate into the metabolites of the CL pathway was accompanied by formation of 14C-labelled monolyso- and dilyso-CL. Labelling of dilyso-CL was increased or decreased by stimulation or inhibition respectively of mitochondrial phospholipase A2. These data suggest a rapid deacylation of newly formed [14C]CL by phospholipase A2, whereas endogenous mitochondrial CL was very resistant to hydrolytic degradation. Unlike dilyso-CL, monolyso-CL could be reacylated by [14C]linoleoyl residues. [14C]Linoleoyl incorporation into CL was also observed when exogenous CL was added instead of monolyso-CL, thus indicating the concerted action of de- and re-acylation. Although 1-palmitoyl-2-[14C]linoleoyl phosphatidylcholine was a suitable acyl donor under experimental conditions, the reaction was not a transacylation but required splitting of [14C]linoleic acid from phosphatidylcholine and formation of [14C]linoleoyl-CoA as an intermediate. The [14C]linoleoyl was mainly bound to the sn-2(2") position of CL, and a small portion (about 20%) to the sn-1(1") position. It is concluded that a cycle, comprising CL deacylation and monolyso-CL reacylation by linoleoyl-CoA, provides a potential mechanism for the remodelling of molecular species of newly formed CL. PMID- 2268288 TI - Human liver steroid sulphotransferase sulphates bile acids. AB - The sulphation of bile acids is an important pathway for the detoxification and elimination of bile acids during cholestatic liver disease. A dehydroepiandrosterone (DHEA) sulphotransferase has been purified from male and female human liver cytosol using DEAE-Sepharose CL-6B and adenosine 3',5' diphosphate-agarose affinity chromatography [Falany, Vazquez & Kalb (1989) Biochem. J. 260, 641-646]. Results in the present paper show that the DHEA sulphotransferase, purified to homogeneity, is also reactive towards bile acids, including lithocholic acid and 6-hydroxylated bile acids, as well as 3 hydroxylated short-chain bile acids. The highest activity towards bile acids was observed with lithocholic acid (54.3 +/- 3.6 nmol/min per mg of protein); of the substrates tested, the lowest activity was detected with hyodeoxycholic acid (4.2 +/- 0.01 nmol/min per mg of protein). The apparent Km values for the enzyme are 1.5 +/- 0.31 microM for lithocholic acid and 4.2 +/- 0.73 microM for taurolithocholic acid. Lithocholic acid also competitively inhibits DHEA sulphation by the purified sulphotransferase (Ki 1.4 microM). No evidence was found for the formation of bile acid sulphates by sulphotransferases different from the DHEA sulphotransferase during purification work. The above results suggest that a single steroid sulphotransferase with broad specificity encompassing neutral steroids and bile acids exists in human liver. PMID- 2268289 TI - Interaction of heparin with fibronectin and isolated fibronectin domains. AB - Fluorescence polarization, gel exclusion chromatography and affinity chromatography were used to characterize the interaction of heparins of different size with human plasma fibronectin (Fn) and several of its isolated domains. The fluid-phase interaction of Fn with heparin was dominated by the 30 kDa and 40 kDa Hep-2 domains located near the C-terminal ends of the A and B chains respectively. The 30 kDa Hep-2A domain from the heavy chain was indistinguishable from the 40 kDa Hep-2B domain in this respect; the presence of an additional type III homology unit in the latter had no effect on the binding. Evidence was provided that each Hep-2 domain has two binding sites for heparin. The N-terminal Hep-1 domain reacted weakly in fluid phase even though it binds strongly to immobilized heparin. Fn and Hep-2 fragments were rather undiscriminating in their reaction with fluoresceinamine-labelled heparins of different sizes. However, oligosaccharides smaller than the tetradecasaccharide (14-mer) bound Fn with a 5 10-fold lower affinity. These results suggest that the Hep-2 domains of Fn are able to recognize a broad spectrum of oligosaccharides that presumably vary significantly with respect to the amount and spatial distribution of charge. PMID- 2268290 TI - Klebsiella pneumoniae nitrogenase. Mechanism of acetylene reduction and its inhibition by carbon monoxide. AB - The electron flux through the MoFe-protein of nitrogenase from Klebsiella pneumoniae determines the absolute and relative rates of 2H+ reduction to H2 and acetylene (C2H2) reduction to ethylene (C2H4) at saturating levels of reductant (Na2S2O4) and MgATP. High electron flux, induced by a high Fe-protein (Kp2)/MoFe protein (Kp1) ratio, favours C2H2 reduction. These data can be explained if ethylene, the two-electron reduction product of C2H2, is not released until three electrons have been transferred from Kp2 to Kp1. This explanation is also consistent with a pre-steady-state lag phase for C2H4 formation of 250 ms observed when functioning enzyme is quenched with acid. Electron flux through nitrogenase is inhibited by C2H2 at high protein concentrations. This is because the association rate between Kp1 and oxidized Kp2 is enhanced by C2H2, leading to an increased steady-state concentration of the inhibitory complex Kp2oxKp1C2H2. This effect is not relieved by CO. Thus CO and C2H2 (or C2H4) must be bound at the same time to distinct sites, presumably at Mo or Fe centres, on the enzyme. PMID- 2268291 TI - Production of recombinant sarcotoxin IA in Bombyx mori cells. AB - A cDNA for sarcotoxin IA, an antibacterial protein of Sarcophaga peregrina (fleshfly), was inserted into a silkworm baculovirus vector and expressed in Bm-N cells, a line of Bombyx mori cells. When a cysteine proteinase inhibitor, p chloromercuribenzenesulphonic acid, was present in the culture medium, a significant amount of recombinant sarcotoxin IA accumulated, but without this reagent the product seemed to be degraded in this system. The C-terminus of the recombinant sarcotoxin IA seemed to be glycine, not amidated arginine as found in authentic sarcotoxin IA. Probably, Bm-N cells lack the C-terminal alpha-amidation enzyme. PMID- 2268292 TI - Increased hepatic lipase activity and increased direct removal of very-low density lipoprotein remnants in Watanabe heritable hyperlipidaemic (WHHL) rabbits treated with ethinyl oestradiol. AB - We studied the effects of ethinyl oestradiol on the serum concentrations and metabolism of very-low- and low-density lipoproteins (VLDL and LDL) in Watanabe heritable hyperlipidaemic (WHHL) homozygous rabbits, an animal model for familial hypercholesterolaemia. The results were compared with those in untreated homozygotes as well as in heterozygotes treated or not with ethinyl oestradiol. The gain in body weight was similar in all groups. Treatment with ethinyl oestradiol resulted in the homozygotes in an approx. 80% decrease in the concentrations of lipids and apoprotein B in the d less than 1.019 lipoprotein fraction; those in the LDL fraction did not change. In the heterozygotes, basal serum lipids and apoprotein B levels in the d less than 1.019 fraction were low; ethinyl oestradiol treatment especially affected the LDL fraction (cholesterol 84%, apoprotein B -64%). Turnover experiments with 125I-labelled VLDL revealed that, on treatment with ethinyl oestradiol, the fractional catabolic rate in homozygous rabbits increased 2-fold. The secretion rates of lipids and protein in the d less than 1.019 fraction as estimated after injection of Triton WR-1339 was not decreased. In homozygotes and heterozygotes increases in post-heparin hepatic lipase activity of 62 and 80% respectively were observed, with no changes in lipoprotein lipase activity. We conclude that ethinyl oestradiol induces in homozygous WHHL rabbits a direct removal of VLDL and VLDL remnants from the plasma, apparently due to an increase in hepatic lipase activity. PMID- 2268293 TI - Translation of preprochymosin in vitro. Evidence for folding of prochymosin to the native conformation. AB - 1. The cDNA coding for preprochymosin has been sub-cloned into the transcription/translation vector pGEM-3Z, the T7 promoter used to transcribe the gene and the product expressed in an 'in vitro' cell-free system comprising rabbit reticulocyte lysate and dog pancreatic microsomes. 2. Translations in various conditions, and analyses of the translation product in reducing and non reducing conditions, indicate that oxidizing translation conditions and the cleavage of the N-terminal 'pre-' sequence are essential for generation of a disulphide-bonded translation product. 3. The disulphide-bonded translation product was resistant to proteinases, as expected for a translation product segregated within microsomal vesicles; in the presence of detergent to solubilize the membranes, the product was not readily susceptible to proteolysis, and was converted to a proteinase-resistant core fragment. 4. Segregated prochymosin, synthesized in reducing conditions, was completely degraded by proteinases under similar conditions. 5. Proteinase treatment of purified recombinant prochymosin gave rise to a proteinase-resistant fragment of similar Mr, suggesting that the disulphide-bonded product of translation in vitro was correctly folded. 6. The translocated, disulphide-bonded and folded prochymosin could be converted into pseudochymosin at pH 2.0, and addition of chymosin to the activation mixture resulted in increased pseudochymosin production. PMID- 2268295 TI - Isolation and properties of a metalloproteinase from buckwheat (Fagopyrum esculentum) seeds. AB - A homogeneous preparation of metalloproteinase, purified 1000-fold, was obtained from buckwheat (Fagopyrum esculentum) seeds. The Mr of the enzyme, determined by SDS/PAGE, was 34,000 (it was 39,000 by gel chromatography). Its pH optimum was 8.0-8.2 with 13 S globulin, from buckwheat seeds, as substrate. Atomic-absorption spectroscopy revealed the presence of one Zn2+ ion per enzyme molecule. The enzyme was completely inhibited by EDTA (1 mM), zincone (1 mM) and 1, 10 phenanthroline (1 mM). The metalloproteinase performed limited proteolysis of the following seed storage proteins: 13 S globulin from buckwheat seeds and 11 S globulin from soybean (Glycine max) seeds. It hydrolysed three peptide bonds formed by the amino groups of Leu15, Tyr16 and Phe25 in the oxidized B-chain of insulin. In its main properties the enzyme is similar to metalloproteinases of animal and bacterial origin. PMID- 2268294 TI - Effect of level of dietary protein on arginine-stimulated citrulline synthesis. Correlation with mitochondrial N-acetylglutamate concentrations. AB - Increases in dietary protein have been reported to increase the rate of citrulline synthesis and the level of N-acetylglutamate in liver. We have confirmed this effect of diet on citrulline synthesis in rat liver mitochondria and show parallel increases in N-acetylglutamate concentration. The magnitude of the effect of arginine in the suspending medium on citrulline synthesis was also dependent on dietary protein content. Mitochondria from rats fed on a protein free diet initially contained low levels of N-acetylglutamate, and addition of arginine increased the rate of its synthesis. Citrulline synthesis and acetylglutamate content in these mitochondria increased more than 5-fold when 1 mM-arginine was added. A diet high in protein results in mitochondria with increased N-acetylglutamate and a high rate of citrulline synthesis; 1 mM arginine increased citrulline synthesis in such mitochondria by only 36%. The concentration of arginine in portal blood was 47 microM in rats fed on a diet lacking protein, and 182 microM in rats fed on a diet containing 60% protein, suggesting that arginine may be a regulatory signal to the liver concerning the dietary protein intake. The rates of citrulline synthesis were proportional to the mitochondrial content of acetylglutamate in mitochondria obtained from rats fed on diets containing 0, 24, or 60% protein, whether incubated in the absence or presence of arginine. Although the effector concentrations are higher than the Ka for the enzymes, these results support the view that concentrations of both arginine and acetylglutamate are important in the regulation of synthesis of citrulline and urea. Additionally, the effects of dietary protein level (and of arginine) are exerted in large part by way of modulation of the concentration of acetylglutamate. PMID- 2268296 TI - Fate of injected glucagon taken up by rat liver in vivo. Degradation of internalized ligand in the endosomal compartment. AB - The uptake and processing of glucagon into liver endosomes were studied in vivo by subcellular fractionation. After injection of [[125I]iodo-Tyr10]glucagon and [[125I]iodo-Tyr13]glucagon to rats, the uptake of radioactivity into the liver was maximum at 2 min (6% of the dose/g of tissue). On differential centrifugation, the radioactivity in the homogenate was recovered mainly in the nuclear (N), microsomal (P) and supernatant (S) fractions, with maxima at 5, 10 and 40 min, respectively; recovery of radioactivity in the mitochondrial lysosomal (ML) fraction did not exceed 6% and was maximal at 20 min. On density gradient centrifugation, the radioactivity associated first (2-10 min) with plasma membranes and then (10-40 min) with Golgi-endosomal (GE) fractions, with 2 5-fold and 20-150-fold enrichments respectively. Subfractionation of the GE fractions showed that, unlike the Golgi marker galactosyltransferase, the radioactivity was density-shifted by diaminobenzidine cytochemistry. Subfractionation of the ML fraction isolated at 40 min showed that more than half of the radioactivity was recovered at lower densities than the lysosomal marker acid phosphatase. Throughout the time of study, the [125I]iodoglucagon associated with the P, PM and GE fractions remained at least 80-90% trichloroacetic acid (TCA)-precipitable, whereas that associated with other fractions, especially the S fraction, became progressively TCA-soluble. On gel filtration and h.p.l.c., the small amount of degraded [125I]iodoglucagon associated with GE fractions was found to consist of monoiodotyrosine. Chloroquine treatment of [125I]iodoglucagon injected rats caused a moderate but significant increase in the late recovery of radioactivity in the ML, P and GE fractions, but had little effect on the association of the ML radioactivity with acid-phosphatase-containing structures. Chloroquine treatment also led to a paradoxical decrease in the TCA precipitability of the radioactivity associated with the P and GE fractions. Upon h.p.l.c. analysis of GE extracts of chloroquine-treated rats, at least four degradation products less hydrophobic than intact [125I]iodoglucagon were identified. Radio-sequence analysis of four of these products revealed three cleavages, affecting bonds Ser2-Gln3, Thr5-Phe6 and Phe6-Thr7. When GE fractions containing internalized [125I]iodoglucagon were incubated in iso-osmotic KCl at 30 degrees C, a rapid generation of TCA-soluble products was observed, with a maximum at pH 4. We conclude that endosomes are a major site at which internalized glucagon is degraded, endosomal acidification being required for optimum degradation. PMID- 2268297 TI - Isolation and characterization of BanLec-I, a mannoside-binding lectin from Musa paradisiac (banana). AB - A lectin (BanLec-I) from banana (Musa paradisiac) with a binding specificity for oligomannosidic glycans of size classes higher than (Man)6GlcNAc was isolated and purified by affinity chromatography on a Sephadex G-75 column. It did not agglutinate untreated human or sheep erythrocytes, but it did agglutinate rabbit erythrocytes. BanLec-I stimulated T-cell proliferation. On size-exclusion chromatography, BanLec-I has a molecular mass of approx. 27 kDa, and on SDS/PAGE the molecular mass is approx. 13 kDa. The isoelectric point is 7.2-7.5. BanLec-I was found to be very effective as a probe in detecting glycoproteins, e.g. on nitrocellulose blots. PMID- 2268298 TI - The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo. AB - The removal from the blood and the uptake by the liver of injected very-low density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time. PMID- 2268299 TI - Involvement of an NAD(P)H oxidase as a pO2 sensor protein in the rat carotid body. AB - The rat carotid body tissue reveals a photometrically measurable haem signal with absorbance maxima at 560 nm, 518 nm and 425 nm, suggesting the presence of a b type cytochrome; this was confirmed by pyridine haemochrome and CO spectra. The quantity of cytochrome b was estimated to be 310 pmol.mg of protein-1. This haem is capable of H2O2 formation, which can be inhibited by 10 microM diphenyliodonium (DPI). The hypoxia-induced increase in nervous chemoreceptor discharge and the reduction of FAD and NAD(P)+ were also inhibited by DPI (10 microM). These results suggest that an oxidase such as the NAD(P)H oxidase of neutrophils may act as a pO2 sensor protein in the rat carotid body, probably inducing the pO2 chemoreceptor process by H2O2 formation. PMID- 2268300 TI - Regulation of skeletal-muscle AMP deaminase. Evidence for a highly pH-dependent inhibition by ATP of the homogeneous derivative of the rabbit enzyme yielded by limited proteolysis. AB - Limited proteolysis of rabbit skeletal-muscle AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) with trypsin results in conversion of the enzyme into a species which over the pH range 6.5-7.1 exhibits hyperbolic kinetics at low K+ concentration even in the absence of ADP, but shows a 20% decrease in activity at saturating substrate concentration. Analysis by sedimentation-equilibrium techniques reveals the proteolysed enzyme to be homogeneous and to have a molecular mass of 222,000 Da, indicative of a trimeric structure with a subunit molecular mass of 72,000 Da, in contrast with the tetrameric structure of the native enzyme, composed of four 79,000-Da subunits. These observations suggest a role of the 7,000-Da fragment which is removed by proteolysis in the maintenance of the three dimensional structure of the subunit that causes the enzyme at low K+ concentration to show homotropic positive co-operativity. Study of the influence of pH, isolated from that of K+, on the kinetics of AMP deaminase reveals a highly pH-dependent inhibitory effect by ATP which is completely absent at acid pH values and abruptly manifests itself just above neutrality. This phenomenon may have significance in the metabolism of exercising muscle, in connection with the pH-dependent interaction of AMP deaminase with the thick filament. PMID- 2268302 TI - Conformational changes in Chondrus crispus flavodoxin on dissociation of FMN and reconstitution with flavin analogues. AB - The apoflavodoxin produced by precipitation of Chondrus crispus flavodoxin with trichloroacetic acid migrates as a single molecular species on non-denaturing PAGE, but at a much lower Rm than the flavoprotein. Values of s and D were significantly lower than for the flavodoxin, but their substitution in the Svedberg equation indicated the molecular mass was closely similar to that of the flavodoxin. This was confirmed by meniscus-depletion sedimentation-equilibrium studies. The Stokes radius of the apoflavodoxin was 3.65 nm, compared with 2.33 nm for the flavodoxin, and estimates of frictional coefficient ratio suggested the apoprotein was in extended conformation compared with the roughly globular shape of the flavodoxin. The Ka for FMN binding was 2.8 x 10(8)M, and the electrophoretic and physicochemical properties of the reconstituted flavoprotein were closely similar to those of the native flavodoxin. FAD, iso-FMN and thio-FMN were also bound effectively, but methyl-FMN and riboflavin were bound only weakly, if at all. The reconstituted flavoproteins were active to various extents in mediating electron transfer from NADPH to cytochrome c catalysed by flavodoxin NADP+ oxidoreductase, the highest activity being with the thio-FMN flavodoxin. PMID- 2268301 TI - Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor. AB - A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain. PMID- 2268303 TI - The role of the 5'-flanking sequence of a human tRNA(Glu) gene in modulation of its transcriptional activity in vitro. AB - The role of a tRNA-like structure within the 5'-flanking sequence of a human tRNA(Glu) gene in the modulation of its transcription in vitro by HeLa cell extracts has been investigated using several deletion mutants of a recombinant of the gene which lacked part or all of the tRNA-like structure. The transcriptional efficiency of four mutants was the same as that of the wild-type recombinant, two mutants had decreased transcriptional efficiency, one was more efficient, and one, lacking part of the 5' intragenic control region, was inactive. Correlation of the transcriptional efficiencies with the position and the size of the 5' flanking sequence that was deleted indicated that the tRNA-like structure may be deleted without loss of transcriptional efficiency. Current models for the modulation of tRNA gene transcription by the 5'-flanking sequence are assessed in the light of the results obtained, and a potential model is presented. PMID- 2268305 TI - Increased association of ribosomes with myofibrils during the skeletal-muscle hypertrophy induced either by the beta-adrenoceptor agonist clenbuterol or by tenotomy. AB - Ribosome distribution in skeletal-muscle myofibres was investigated by immunohistochemistry and microdensitometry by using anti-(60 S ribosomal subunit) antibodies. Administration of the beta-adrenoceptor agonist clenbuterol caused an increase in the staining of the myofibrillar region with this antibody relative to that found in the subsarcolemmal cytoplasm. A similar effect was observed during hypertrophy of the plantaris muscle following severance of the tendon to the gastrocnemius. The results suggest that increased association of ribosomes with the myofibrils occurs during muscle hypertrophy. PMID- 2268304 TI - Characterization of Shiga-like toxin I B subunit purified from overproducing clones of the SLT-I B cistron. AB - The cistron encoding the B subunit of Escherichia coli Shiga-like toxin I (SLT-I) was cloned under control of the tac promoter in the expression vector pKK223-3 and the SLT-I B subunit was expressed constitutively in a wild-type background and inducibly in a lacIq background. The B subunit was located in the periplasmic space, and less than 10% was found in the culture medium after 24 h incubation. Polymyxin B extracts contained as much as 160 micrograms of B subunit/ml of culture. B subunit was purified to homogeneity by ion-exchange chromatography followed by chromatofocusing. Cross-linking analysis of purified native B subunit showed that it exists as a pentamer. In gels containing 0.1% SDS the native protein dissociated into monomers. B subunit was found to have the same glycolipid-receptor-specificity as SLT-I holotoxin. Competitive binding studies showed that B subunit and holotoxin had the same affinity for the globotriosylceramide receptor. We conclude that this recombinant plasmid is a convenient source of large amounts of purified SLT-I B subunit, which could be used for biophysical and structural studies or as a natural toxoid. PMID- 2268307 TI - The mechanism of potassium movement across the liposomal membrane. AB - Addition of potassium to sodium-loaded asolectin liposomes induces an internal alkalinization even in the absence of ionophores. Most of the K+ entry is electrogenic, as shown by fluorescent changes in the potential-sensitive probe Oxonol V. The major part of the proton efflux observed must therefore be electrophoretic. However, in the presence of high concentrations of membrane permeable n-butyltriphenylphosphonium, potassium addition induces a residual alkalinization under conditions where no membrane potential can be observed with Oxonol V. This suggests that liposomes also catalyze direct electroneutral K+/H+ exchange, as has been theoretically predicted for cytochrome oxidase proteoliposomes (Wrigglesworth, J.M., Cooper, C.E., Sharpe, M.A. and Nicholls, P. (1990) Biochem. J. 270, 109-118). Free fatty acids present in the soybean phospholipid mixture may be responsible for such activity. PMID- 2268306 TI - Evidence that use of Triton WR1339 underestimates the triacylglycerol entry rate into the plasma of lactating rats owing to continued accumulation of lipid in the mammary gland. AB - Measurement of the entry rate of an intragastric load of [14C]triolein into the plasma in the presence of Triton WR1339 gave similar values for virgin and weaned rats, but significantly lower values for lactating rats. This decreased entry rate (65%) in lactating compared with virgin rats was due to a failure of Triton WR1339 to inhibit the accumulation of [14C]lipid in the mammary gland. This is further evidence that mammary-gland lipoprotein lipase behaves differently from that in white adipose tissue or muscle. PMID- 2268308 TI - Definition of the transcription initiation site of human plasminogen gene in liver and non hepatic cell lines. AB - We have mapped the cap site of the human plasminogen mRNA by primer extension and PCR techniques and found that it is located at position -161 relative to the first ATG, 97 bases upstream to the 5' end of the previously isolated cDNA clone. Seven human hepatic and non hepatic cell lines and fresh liver cells were tested for human plasminogen mRNA expression: the liver and the liver derived HepG2 cell line represent the major site of plasminogen RNA synthesis while the other cell lines (Hep3B, HeLa, IMR, 293 CaCo and SW626) show much lower levels. PMID- 2268309 TI - Structure and expression of the human polymorphic epithelial mucin gene: an expressed VNTR unit. AB - The human polymorphic epithelial mucin (PEM) is expressed apically by glandular epithelium and by the carcinomas that develop from these tissues. Previously isolated cDNA clones revealed that the core protein contained a large domain consisting of variable numbers of 60 bp tandem repeats (TR), making it an expressed minisatellite. We now report the full genomic sequence of the PEM gene, including 803 bp of 5' flanking sequence. The gene is composed of 7 exons and varies in size from approximately 4 to approximately 7 kb, depending on the number of tandem repeats in exon 2. Expression of PEM was obtained from a genomic clone in an Epstein-Barr virus based vector, after transfection into a human epithelial cell line, indicating the presence of effective regulatory sequences in this clone. PMID- 2268310 TI - Molecular analysis of an acatalasemic mouse mutant. AB - The Csb acatalasemia mouse mutant differentially expresses reduced levels of catalase activity in a tissue specific manner. In order to pinpoint the molecular lesion that imparts the acatalasemia phenotype in Csb mice we have utilized the polymerase chain reaction technique to isolate catalase cDNA clones from control and Csb mouse strains. Sequence analyses of these cDNA clones have revealed a single nucleotide difference within the coding region of catalase between control and Csb mice. This nucleotide transversion (G----T) is located in the third position of amino acid 11 in the catalase monomer. In control mouse strains glutamine (CAG) is encoded at amino acid 11, while in Csb mice this codon (CAT) encodes histidine. This amino acid is located within a region that forms the first major alpha-helix in the amino-terminal arm of the catalase subunit and, as such, may render the catalase molecule unstable under certain physiological conditions. PMID- 2268311 TI - Expression of a silkworm eclosion hormone gene in yeast. AB - Recombinant silkworm eclosion hormone was produced for the first time in yeast which was transformed with a shuttle plasmid containing a construct coding a signal peptide and the mature sequence of the silkworm eclosion hormone. Successfully transformed yeast processed recombinant silkworm eclosion hormone I (EH-I) and transported it to periplasm at the concentration of 60 micrograms per liter of culture. The biological activity of the purified recombinant silkworm eclosion hormone exhibited the ED50 value of 0.2 ng which is the same as that of the authentic hormone isolated from the silkworm brain. PMID- 2268312 TI - Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor. AB - Tumor necrosis factor (TNF) is synthesized as a prohormone with an unusually long and atypical signal sequence which is absent from the mature secreted cytokine. In addition to mature 17 kDa TNF, LPS-stimulated murine macrophages secrete at least seven TNF-like proteins (isoforms) of differing electrophoretic mobility which appear as a "ladder" on SDS-PAGE. We here present data indicating that these isoforms derive not from sequential clipping of propiece fragments, but rather from differential glycosylation at sites on the mature hormone. Selected isoforms have been isolated and purified by sequential chromatographic and electrophoretic steps. NH2-terminal sequence analysis of two of these isoforms reveal sequences identical to that of mature 17 kDa murine TNF. Characterization of the secretory products of tunicamycin-treated. LPS-stimulated murine macrophages indicate that the "ladder" complex reflects differential glycosylation of mature 17 kDa TNF. Digestion of purified isoforms with a battery of glycosidic enzymes indicate that secreted forms of murine TNF contain both sialic acid and asparagine(N)-linked chains. The biological significance of this heterogeneity is not known. PMID- 2268313 TI - Isolation and characterization of a galactose-specific carbohydrate binding protein from human lymphoblastic cells. AB - A carbohydrate binding protein of Mr = 32,000 (CBP 32) has been isolated from detergent extracts of human B and T lymphoblastoid cells. CBP 32 binds specifically to glycoproteins containing asparagine-linked complex oligosaccharides, and can be eluted from a fetuin affinity matrix by beta lactose. Binding is not thiol dependent, nor are divalent cations necessary for binding. Native CBP 32 appears to exist as a monomer, with a pI of 8.2. Purified CBP 32 can bind detergent, as shown by charge-shift electrophoresis, and thus appears to be an integral membrane protein. PMID- 2268314 TI - Biotransformations of R-(+)-pulegone and menthofuran in vitro: chemical basis for toxicity. AB - Incubation of R-(+)-pulegone(I) with PB-induced rat liver microsomes in the presence of NADPH resulted in the formation of menthofuran (II) and 2-Z-[2'-keto 4'-methylcyclohexylidene] propanol (III, 9-hydroxy pulegone) as the major and minor metabolites, respectively. When isopulegone (IV) was used as the substrate, the major metabolite formed was shown to have identical GC-MS fragmentation pattern to that of synthetic 2-[2'-keto-4'-methylcyclohexyl]prop-2-en-1-ol (V) and the minor metabolite was shown to be menthofuran (II). Transformation of menthofuran (II) by microsomes in the presence of NADPH yielded a metabolite identified as 2-Z-(2'-keto-4'-methyl cyclohexylidene) propanal (VI, pulegone-8 aldehyde). Formation of this alpha, beta -unsaturated aldehyde was further confirmed by trapping it as cinnoline derivative by adding semicarbazide to the assay medium. The toxicity mediated by pulegone is discussed in the light of these observations. PMID- 2268315 TI - Calcium protects pituitary basic fibroblast growth factors from limited proteolysis by co-purifying proteases. AB - Extracts from bovine pituitaries and other tissues contained basic fibroblast growth factor-like peptides of 22-26 kda, co-fractionating with smaller, 16-20 kda bFGFs. Heparin-bound, 22-26 kda bFGFs were converted to smaller, heparin binding forms by tryptic proteolysis. In solution, 22-26 kda bFGFs were converted to smaller, heparin-binding forms by an activity present in pituitary extracts. Calcium protected higher molecular weight pituitary bFGFs from truncation by the endogenous activity, which was not acid-activated, co-purified with bFGF during heparin-sepharose chromatography, remained operant at high salt concentrations and was inhibited by phenylmethan-sulfonyl fluoride. PMID- 2268316 TI - LAMP-1 in CHO cells is a primary carrier of poly-N-acetyllactosamine chains and is bound preferentially by a mammalian S-type lectin. AB - Recent studies indicate that some mammalian S-type lectins bind preferentially to oligosaccharides containing the repeating disaccharide [3Gal beta 1,4GlcNAc beta 1]n or poly-N-acetyllactosamine (PL) sequence. We report here our investigation on the distribution of these sequences in glycoproteins in Chinese hamster ovary (CHO) cells and the interaction of glycoproteins containing PL chains with an immobilized S-type lectin (L14) from calf heart tissue. Our results demonstrate that PL chains are carried by a few high molecular weight glycoproteins which are bound by tomato-lectin Sepharose and one of these was precipitated by antibody to LAMP-1 (a lysosomal-associated membrane glycoprotein). More importantly, these high molecular weight glycoproteins, including LAMP-1, were bound with high affinity by L14. These results indicate that mammalian S-type lectins are highly specific in their interactions with glycoproteins and that LAMPs carry important recognition sequences for these lectins. PMID- 2268317 TI - Aortic smooth muscle cells are able to convert angiotensin I to angiotensin II. AB - The role of vascular smooth muscle cells (VSMC) in the intraparietal conversion of angiotensin I (AngI) to angiotensin II (AngII) was investigated in rat aortic tissue. The responses of rat aortic vascular smooth muscle cells to AngI and AngII were assessed by studying contraction of endothelium-denuded aortic rings and by measuring intracellular Ca++ ion concentration in primary cultures of VSMC free of endothelial cells. In both preparations, AngI and AngII induced identical responses which were inhibited by saralasin, a blocker of AngII receptors. In the presence of captopril, an inhibitor of the angiotensin converting enzyme, the increase in calcium caused by AngI was abolished in VSMC cultures and the contractile effect of this peptide in aortic rings was strongly decreased, whereas the responses to AngII remained unaffected. These results demonstrate that VSMC are able to convert AngI to AngII. PMID- 2268318 TI - Identification of type I iodothyronine 5'-deiodinase as a selenoenzyme. AB - A 27.8 kDa membrane selenoprotein was previously identified in rat thyroid, liver and kidney, the tissues with the highest activities of type I iodothyronine 5' deiodinase. This membrane enzyme catalyzes the deiodination of L-thyroxine to the biologically active thyroid hormone 3,3',5-triiodothyronine. A decrease in the activity of this enzyme, observed here in the liver of selenium-deficient rats, was found to be due to the absence of a selenium-dependent membrane-bound component. By chemical and enzymatic fragmentation of the 75Se-labeled selenoprotein and of the 27 kDa substrate binding type I 5'-deiodinase subunit, affinity-labeled with N-bromoacetyl-[125I]L-thyroxine, and comparison of the tracer distribution in the peptide fragments the identity of the two proteins was shown. The data indicate that the deiodinase subunit contains one selenium atom per molecule and suggest that a highly reactive selenocysteine is the residue essential for the catalysis of 5'-deiodination. From the results it can be concluded that type I iodothyronine 5'-deiodinase is a selenoenzyme. PMID- 2268319 TI - Pancreastatin: characterization of biological activity. AB - Pancreastatin (PST) (1-49) was first isolated from the porcine pancreas and can inhibit glucose-induced insulin release. PST (33-49), a PST C-terminal fragment, can also inhibit insulin release. The purpose of this study was to determine the shortest C-terminal biologically active fragment of PST, in terms of inhibition of insulin release from the isolated perfused rat pancreas. Porcine PST (1-49) and C-terminal fragments, PST (33-49), PST (35-49), PST (37-49) and PST (39-49) were synthesized by solid-phase methodology. PST (1-49), PST (33-49) and PST (35 49), at 10 nM, significantly (p less than 0.05) inhibited insulin release from isolated perfused rat pancreas: the first phase was inhibited by 15.6 +/- 2.4, 24.4 +/- 6.5 and 12.5 +/- 1.9% and the second phase, 18.9 +/- 2.7, 25.7 +/- 4.8 and 20.1 +/- 1.9% by PST (1-49), PST (33-49) and PST (35-49), respectively. PST (35-49) shows a dose-dependent inhibition of insulin release. PST (37-49) and PST (39-49) were, however, inactive. Our results indicate that the shortest C terminal biologically active fragment is PST (35-49). These data further indicate that the C-terminal portion of PST is primarily responsible for the biological activity of PST. PMID- 2268320 TI - Granulins, a novel class of peptide from leukocytes. AB - We report the isolation and characterization of a novel class of leukocyte peptides with possible cytokine-like activities which we call granulins. They are cystine-rich with molecular weights of approximately 6 Kda, except for granulin D, which appears to be a dimer. We present the sequence of one member of this family, a 56 residue peptide, granulin A, and amino-terminal sequences for three other granulins from human peripheral leukocytes. A fifth related peptide was isolated and partially sequenced from rat bone marrow, suggesting that at least some of the granulin in peripheral leukocytes is preformed in the marrow. Rat granulin, and human granulin A, are closely related, showing that the granulin structures are highly conserved between species. PMID- 2268321 TI - The Cu,Zn superoxide dismutase isoenzymes of Xenopus laevis: purification, identification of a heterodimer and differential heat sensitivity. AB - The three Cu,Zn superoxide dismutase electromorphs of the amphibian Xenopus laevis were purified by an original procedure. N-terminal sequence analysis demonstrated that they are two different homodimers (AA and BB) and a hybrid heterodimer (AB), arising from the co-expression of duplicated genes. The three forms have the same pI, same enzyme activity and EPR spectra, but different heat sensitivity, form BB being more resistant than form AA, with form AB showing intermediate sensitivity. Thermostability of BB and the control bovine enzyme was enhanced by a tenfold increase in protein concentration. It is suggested that the higher heat sensitivity of the AA isoenzyme is related to the presence of an extra Cys residue and to an easier dissociation of the protein dimer into monomers. PMID- 2268322 TI - Introduction of a non-native disulfide bridge to human lysozyme by cysteine scanning mutagenesis. AB - To examine whether the disulfide bridge between residues 65 and 81 can be replaced by a non-native disulfide bridge in the mutant h-lysozyme C77/95A and whether the formation of such a new disulfide bridge affects the folding of the protein, cysteine scanning mutagenesis has been performed within two discontinuous segments (residues 61-67 for the mutant C65/77/95A, and 74-84 for the mutant C77/81/95A). The position of the Cys residue at 65 or 81 was continuously shifted by site-directed mutagenesis. Of the mutants, only substitution of Cys for Trp64 allowed the secretion of mutant h-lysozyme(W64C) into the medium in a sufficient amount for analysis. After the purification, the mutant enzyme was obtained as two components (W64C-A and W64C-B). The only difference between A and B was that A had a peptide bond cleaved between Ala77 and His78. A non-native disulfide bridge between residues 64-81 was found in both components. Little difference was observed in CD spectra among wild-type and mutant enzymes. It is likely that the tertiary structure of the W64C mutant might be distorted at the location, because the directions of amino acid side chains at positions of 64 and 81 are shown to be opposite to each other in wild-type h lysozyme by X-ray crystallographic analysis. PMID- 2268323 TI - Cloning and sequence analysis of mink growth hormone cDNA. AB - A cDNA clone for mink growth hormone (GH) was isolated from a mink pituitary cDNA library, employing a part of rat growth hormone cDNA sequence as a probe. According to the nucleotide sequence, mature mink GH consists of 190 amino acids with a calculated molecular weight of 21,720. The amino acid sequence homology between the mature region of mink GH and those of pig GH, rat GH, bovine GH and human GH was 98.4%, 93.7%, 89.0% and 66.7%, respectively. PMID- 2268324 TI - Cloning of cDNA and amino acid sequence of one of chicken cone visual pigments. AB - The chicken has four kinds of color visual pigments, in addition to rhodopsin. A chicken genomic DNA library was screened with cDNA of human red-sensitive pigment and a chicken genomic DNA fragment including rhodopsin exons 2, 3 and 4, and then a genomic DNA fragment encoding a visual pigment, possibly an iodopsin, was cloned. A cDNA library, constructed from chicken retina mRNA, was screened with the genomic DNA fragment and the cDNA of human red-sensitive pigment, and the cDNA encoding the pigment was cloned. The nucleotide sequence of this cDNA was similar to that of the human red-sensitive pigment, with identities of 78% for the nucleotide sequence and 84% for the amino acid sequence with human red sensitive pigment. PMID- 2268325 TI - Proteolytic processing of porcine big endothelin-1 catalyzed by cathepsin D. AB - Cathepsin D, a candidate for endothelin-converting enzyme (ECE), was allowed to act on porcine big endothelin-1 (big ET-1, 1-39). The proteinase primarily cleaved the Asp18-Ile19 and Trp21-Val22 bonds of big ET-1(1-39), with a optimum pH of 3.5. The mature ET-1(1-21), generated by the cleavage between Trp21 and Val22, was subsequently degraded by removal of most of the C-terminal tripeptide (Ile19-Ile20-Trp21). Therefore, cathepsin D is by no means a specific ECE, although the proteinase does cleave the Trp21-Val22 bond of big ET-1(1-39) to produce mature ET-1(1-21). The possibility that cathepsin D can act as an endothelin-degrading enzyme in vivo warrants consideration. PMID- 2268326 TI - Influences of membrane curvature in lipid hexagonal phases studied by deuterium NMR spectroscopy. AB - The presence of reversed hexagonal phase, HII, favoring lipids in membranes has been proposed to be significant in various biological processes. Therefore an understanding of the HII phase and the transition from the lamellar to hexagonal phase is of importance. We have applied deuterium NMR spectroscopy to study the bilayer and reversed hexagonal phases of 1-perdeuteriopalmitoyl-2-linoleoyl-sn glycero-3-phosphoethanolamin e. The difference in packing between the HII and L alpha phases leads to smaller segmental order parameters in the former case. Since the order profiles are sensitive to the geometry of the aggregates, they can be used to extract structural information about the phases. We present a new means of calculating the radius of curvature, R1, for the HII phase from 2H NMR data. This method gives a value of R1 = 18.1 A, which is in agreement with current understanding of the structure of the HII phase and with x-ray diffraction data. PMID- 2268327 TI - Loss of growth inhibitory activity of TGF-beta toward normal human mammary epithelial cells grown within collagen gel matrix. AB - TGF-beta at concentrations in the range from 0.1 to 10 ng/ml gave significant growth inhibition of nonmalignant human mammary epithelial cells (HMEC) but not of malignant HMEC grown in monolayer cultures in serum-free medium. However, no growth inhibition of the nonmalignant cells was observed when the cells were cultivated within a type-I collagen gel matrix either adhering to a plastic substratum or floating on the medium. Within floating collagen gels, both nonmalignant and malignant HMEC formed a cell mass having radial extensions, and TGF-beta at 1 or 10 ng/ml prevented the formation of extensions only in the nonmalignant HMEC. PMID- 2268328 TI - Interleukin-1 increases norepinephrine turnover in the spleen and lung in rats. AB - To clarify effects of interleukin-1 on sympathetic nerve activity, norepinephrine turnover in various organs was assessed in rats after intraperitoneal injection of recombinant human interleukin-1 beta. Interleukin-1 administration increased norepinephrine turnover in the spleen, lung and hypothalamus without appreciable effect in the heart, liver, submandibular gland, thymus, pancreas, brown adipose tissue and medulla oblongata. Similar changes in norepinephrine turnover were also found after the administration of bacterial endotoxin. It was concluded that interleukin-1 activates the sympathetic nerves specifically in the spleen and lung. PMID- 2268329 TI - Molecular cloning and characterization of cDNA for the precursor of rat pituitary adenylate cyclase activating polypeptide (PACAP). AB - We have isolated and cloned a cDNA for rat pituitary adenylate cyclase activating polypeptide (PACAP) precursor protein from the brain. The nucleotide and the deduced amino acid sequences revealed that the rat PACAP cDNA encoded a 175 amino acid protein highly homologous to the ovine and human PACAP precursors. The rat PACAP precursor protein included a putative signal peptide at the amino-terminus, a PACAP-related peptide (PRP) of 29 amino acid residues and the rat PACAP of 38 amino acid residues flanked by basic processing sites, and a carboxy-teminus amidation signal for PACAP. Furthermore, the amino acid sequence of the rat PACAP was completely identical to that of the ovine and human PACAP. Northern blot analysis of rat brain RNA revealed an approximately 3.0 kb transcript for the PACAP precursor in rat brain. PMID- 2268330 TI - Decrease of calmodulin and actin in the plasma membrane of rat liver cells during proliferative activation. AB - After proliferative activation of rat liver cells in vivo by a partial hepatectomy a decrease of the calmodulin content in the three plasma membrane domains (blood sinusoidal, canalicular and lateral) was observed. At 24 hours after partial hepatectomy calmodulin was found to be 3 fold lower in the sinusoidal and lateral fractions whereas a 2 fold decrease was detected in the canalicular domain. Decreases on the actin levels have been also detected at 24 hours after a partial hepatectomy. Since at this time after surgery increases on nuclear actin and calmodulin have been reported, these results suggest the possibility that the actin and calmodulin dissociated from the plasma membrane after a partial hepatectomy could subsequently be translocated into the nuclei. PMID- 2268331 TI - Immuno-cross-reactivity of histidine and dopa decarboxylases. AB - Immuno-cross-reactivity between histidine decarboxylase (HDC) and dopa decarboxylase (DDC) was investigated. By comparing the cDNA sequences of rat HDC with rat and guinea-pig DDCs, we found a region that may possibly be related to the cross-reactivity of anti-rat HDC antibody with guinea-pig DDC. The peptide encoded by this region was synthesized and anti-peptide antibody was prepared. We also purified HDC and DDC homogeniously from fetal rat liver and guinea-pig liver, respectively. On immunoblotting, anti-peptide antibody recognized both rat HDC and guinea-pig DDC. Anti-HDC polyclonal antibody which also recognizes both enzymes detected only rat HDC when it was absorbed by the peptide. This result indicates that this region is responsible for the immuno-cross-reactivity of anti rat HDC antibody with guinea-pig DDC. PMID- 2268332 TI - Phorbol esters stimulate the transport of anionic amino acids in cultured human fibroblasts. AB - The effect of phorbol esters on the transport of amino acids has been evaluated in cultured human fibroblasts. The activity of the Na(+)-dependent system XAG- for anionic amino acids is selectively and markedly stimulated by phorbol esters. The effect is maximal within 15 min; it is attributable to an increase in transport maximum (Vmax) and not prevented by inhibitors of protein synthesis. The half-maximal stimulation is observed at concentrations of phorbol 12,13 dibutyrate lower than 100 nM. Prolonged incubations in the presence of 1 microM phorbol 12,13-dibutyrate lower the binding of the ligand to its receptor with a loss of the stimulatory effect on transport. The results presented indicate that the stimulation of amino acid transport through system XAG- by phorbol esters requires the activation of protein kinase C. PMID- 2268333 TI - Constitutive and inducible expression of a transgene directed by heterologous promoters in a trout liver cell line. AB - Activities of heterologous promoters and enhancers in cultured rainbow trout liver cells were examined employing the bacterial chloramphenicol acetyltransferase gene as the reporter. SV40 promoter-enhancer and Rous sarcoma virus long terminal repeat directed constitutive expression at high levels. Moloney murine leukemia virus long terminal repeat and SV40 promoter combined with Adenovirus type 2 enhancer were also constitutively expressed. Drosophila Hsp70 promoter was activated when the transformed cells were cultured at 25 degrees C, a higher temperature than the temperature normally used, in faithful response to heat shock. PMID- 2268334 TI - Two different HNF1-like transcription activators in the liver bind to the same region of the rat aldolase B promoter. AB - Coexistence of two different HNF1-like factors (AlF-A1 and AlF-A2) in rat liver is described. The two factors had similar molecular weight and the same sequence specificity in DNA-binding. One of these factors AlF-A1 was retained on wheat germ agglutinin-sepharose column and eluted from it with N-acetylglucosamine, while AlF-A2 was not, suggesting that AlF-A1 is glycosylated. Using rat brain nuclear extract, both factors stimulated transcription in vitro, but their stimulatory effects differed from each other. PMID- 2268335 TI - Selection of deletion mutants by polymerase chain reaction. AB - Polymerase chain reaction (PCR) based DNA amplification has replaced many time consuming protocols in molecular biology. Here we describe a simple strategy to quickly select deletion mutants based on PCR methodology which then can be confirmed by nucleotide sequencing. A forward PCR primer is designed in such a way to recognize only the wild type sequences in the amplification reaction and thus a negative selection identifies the deletion in the samples. PMID- 2268336 TI - Stereochemistry of the epoxidation of fatty acids catalyzed by soybean peroxygenase. AB - The stereochemistry of C18 unsaturated fatty acids epoxidation catalyzed by detergent-solubilized and partially purified soybean peroxygenase was determined by chiral phase HPLC. Linoleic acid was oxidized into 9, 10- and 12,13-cis epoxyoctadecenoic acids with a high enantiofacial selectivity. A 5.2:1 and 2.3:1 ratio respectively in favor of the 9(R), 10(S)- and 12(R), 13(S)-epoxy enantiomers was observed. These epoxy-derivatives of linoleic acid have the chirality of metabolites known to be involved in plant defense against fungi. This finding is of importance in establishing a physiological role for the peroxygenase. PMID- 2268337 TI - Cholesterol efflux from adipose cells is coupled to diacylglycerol production and protein kinase C activation. AB - Apolipoprotein A-I (apo A-I)*/DMPC complexes have been previously shown to promote cholesterol efflux from cholesterol-preloaded adipose cells whereas apo A II/DMPC complexes, which bind to the same cell surface binding sites, were ineffective. Addition of apo A-I/DMPC complexes led to a rapid and transient formation of diacylglycerol. However, in contrast to PGF2 alpha (Doglio et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 1148), no accumulation of inositol phosphates was observed. Apo A-II/DMPC complexes had no effect on diacylglycerol formation. Stimulation by apo A-I/DMPC complexes or native HDL3 of cells prelabelled with (2-palmitoyl 9,10[3H])phosphatidylcholine induced also the formation of labelled diacylglycerol whereas apo A-II/DMPC complexes and HDL3 treated with tetranitromethane showed no effect. Direct activation of protein kinase C(s) by PMA promoted cholesterol efflux providing that DMPC liposomes were present as cholesterol acceptor. It is proposed that lipoprotein particles have two separate effects, i.e. a ligand-induced effect leading to cholesterol translocation from intracellular stores to the cell surface and a bilayer-induced effect allowing cholesterol efflux from the cell surface to the acceptor. PMID- 2268339 TI - Isolation and identification of the gene of cholesterol oxidase from Brevibacterium sterolicum ATCC 21387, a widely used enzyme in clinical analysis. PMID- 2268338 TI - The effect of antifreeze glycopeptides on membrane potential changes at hypothermic temperatures. AB - The research on antifreeze glycopeptides (AFGPs) from Antarctic and Arctic fishes has focused primarily on their interaction with ice crystals. This study reports results of experiments in which pig oocytes, known to be sensitive to hypothermic temperatures, were exposed to 4 degrees C for various periods of time, in solutions of different molecular weight AFGPs from Antarctic nototheniid fishes. The membrane potential was measured across the oolemma following hypothermic exposure. The results show that a physiological combination of the different molecular weight AFGPs protects the structural integrity of the oolemma and inhibits ion leakage across the oolemma at hypothermic temperatures. The results also show that the hypothermic protection is nonlinearly dependent on concentration and that separately, the different molecular weight glycopeptides do not stop ion leakage even at very high concentration. The protection of membranes at hypothermic temperatures is a new property of AFGPs which was not known prior to our work. PMID- 2268340 TI - Regulation of sucrase-isomaltase gene expression along the crypt-villus axis of rat small intestine. AB - The expression of sucrase-isomaltase mRNA was investigated along the crypt-villus axis of rat small intestine using differentially isolated cells and in situ hybridization. A partial rat sucrase-isomaltase cDNA was cloned which coded for a protein that was predicted to be 88% homologous to those encoded by the rabbit and human cDNAs. Southern blot analysis of rat genomic DNA indicated that the cDNA hybridized to a single gene. Northern blots of RNA extracted from subpopulations of intestinal epithelial cells that were isolated from villus and crypt compartments showed that this cDNA hybridized to a 6.5 kb band predominantly in villus RNA. In situ hybridization using 35[S]-labeled RNA probes demonstrated that autoradiographic grains were detected over eptithelial cells located on villi with the greatest number of grains located at the crypt-villus junction and in the lower to mid-villus region; from mid-villus to the villus tip there was a decline in sucrase-isomaltase mRNA. We conclude that expression of sucrase-isomaltase as enterocytes emerge from intestinal crypts is regulated primarily at the level of mRNA accumulation which, most likely, is a result of activation of sucrase-isomaltase gene transcription. PMID- 2268341 TI - Ethanol-induced increases in [Ca2+]i and inositol (1,4,5) triphosphate in rat hepatocytes. AB - Rat hepatocytes were studied for [Ca2+]i with Fura-2 at the single cell level using a microfluorometer-imaging system which showed that both the number of cells elevating [Ca2+]i and the magnitude of [Ca2+]i increase were directly dependent upon ethanol concentration between 50 mM and 1 M. Peak [Ca2+]i increases ranged from 27 nM with 50 mM ethanol to 57 nM after 1 M ethanol. Ethanol appeared to initiate calcium release from intracellular stores and caused a dose dependent production of inositol(1,4,5) triphosphate (Ins(1,4,5)P3) in hepatocytes. Low concentrations of ethanol (50-100 mM) did not significantly raise Ins(1,4,5)P3 although 300 mM-1 M increased Ins(1,4,5)P3 comparable to that found with vasopressin (5 nM). In summary, physiologic amounts of ethanol raise [Ca2+]i in rat hepatocytes, although at lower levels (50-100 mM) the changes may or may not be related to an Ins(1,4,5)P3 pathway. PMID- 2268342 TI - Expression of the calcitonin gene during migration of the Pacific salmon, Oncorhynchus gorbuscha. AB - Plasma calcitonin levels increase during reproduction in female salmon. Whether these changes in circulating levels of the hormone are due to increased secretion and or increased biosynthesis is not established. We measured total and poly A+ RNAs and calcitonin content of ultimobranchial bodies of male and female pink salmon during the different stages of the reproductive cycle. Calcitonin mRNAs were analysed by hybridization of northern and dot blots with a specific probe for salmon calcitonin. Dot blot autoradiography indicated that female animals had higher levels of CT mRNA than males and these values were correlated with plasma calcitonin levels. In conclusion, sexual hormones still to be identified, are probably implicated in the expression of the calcitonin gene in females during the reproductive cycle. PMID- 2268343 TI - One of the two genomic copies of the glycine decarboxylase cDNA has been deleted at a 5' region in a patient with nonketotic hyperglycinemia. AB - One of eight patients with nonketotic hyperglycinemia resulted by the lesion in glycine decarboxylase showed the deletion of 0.6-kb SacI and 1.5-kb PstI fragments identified by the cDNA for this protein. A genomic clone, lambda HGDG10, encodes a 5' region of this cDNA in an organized structure and can produce these two fragments. The other clone, lambda HGDG8, carries a processed gene. Southern analysis using a limited segment of this cDNA demonstrated that the 1.7-kb and 1.5-kb PstI fragments predicted from its recognition sites in both genomic clones occur actually in the human genome, indicating that at least two copies of glycine decarboxylase cDNA exist in the haploid genome, and the patient has the glycine decarboxylase gene deleted at a 5' region. PMID- 2268344 TI - Endothelin releasing activity in calf serum and porcine follicular fluid. AB - Bovine calf serum (CS) and porcine follicular fluid (PFF) added to bovine aortic endothelial cells (BAEC) in culture stimulate endothelin (ET) release. Sorbent extraction of acidified calf serum and PFF using Bond Elut C18 yields a product with an activity 30% that of the starting material. Fractionation of Bond Elut C18 extracted CS or PFF using HPLC yields peaks of activity with retention times similar to those of TGF beta and activin A, respectively. TGF beta is 10-fold more potent than activin A to stimulate ET release from BAECs. The observation that TGF beta and activin A are dose-additive but not effect-additive to stimulate ET release is compatible with the conclusion that these two substances act through a similar mechanism. Thus, TGF beta and/or activin A-related peptides may contribute to the ET releasing activity observed in acidified Bond Elut C18 extracted CS and PFF. The identity of ET-releasing activity in native CS and PFF remains to be established. PMID- 2268345 TI - A point mutation in the mitochondrial tRNA(Leu)(UUR) gene in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). AB - Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episode (MELAS) is a major group of heterogeneous mitochondrial disorders. To identify the defective gene, mitochondrial DNA from a patient with MELAS was sequenced by using amplified DNA fragments as sequencing templates. In 14.1 kbp determined out of 16.6 kbp of the whole mitochondrial gene, at least 21 nucleotides were different from those of a control human mitochondrial DNA. One of the substitutions was a transition of A to G in the tRNA(Leu) (UUR) gene at Cambridge nucleotide number 3,243. This nucleotide is conserved not only in many mitochondrial tRNAs but in most cytosolic tRNA molecules. An Apa I restriction site was gained by the substitution of this nucleotide. The Apa I digestion of the amplified DNA fragment revealed that all independent 6 patients had G at nucleotide number 3,243 in their mitochondrial DNAs, but none of 11 control individuals had G at this position. This result strongly suggests that the mutation in the mitochondrial tRNALeu gene causes MELAS. PMID- 2268346 TI - Camel lens crystallins glycosylation and high molecular weight aggregate formation in the presence of ferrous ions and glucose. AB - The incubation of camel lens cortex homogenate with 100 microM ferrous ions and 5.5 mM glucose under sterile conditions caused rapid protein aggregation, but little or no reaction was seen with either 100 microM ferrous ions or 5.5 mM glucose alone. The formation of glycosylated high molecular weight (HMW) protein aggregates was confirmed by light scattering studies, a decreased level of free SH groups, incorporation of [14C]-glucose and elution of HMW protein aggregate just after the void volume of a Sephacryl S-1000 column. The bonding involved in the formation of these aggregates was found to be mainly disulfide in nature. Isoelectric focusing (IEF) in the presence and absence of reducing conditions indicated that gamma-crystallins may be involved in the formation of HMW protein aggregates. The modifications observed were found to mimic those seen in cataractous lenses. PMID- 2268347 TI - Isoprenoid metabolism in Plasmodium falciparum during the intraerythrocytic phase of malaria. AB - Products of the isoprenoid metabolism were identified upon incubations of extracts from Plasmodium falciparum infected red blood cells with [14C] mevalonate. Uninfected erythrocytes and wild type yeast Saccharomyces cerevisiae extracts were used as controls. In parasitized red blood cells as well as in yeast extracts, mevalonate was converted into the biosynthetic isoprenoid precursors of sterol pathway until farnesyl pyrophosphate. In contrast, no mevalonate conversion was observed in uninfected erythrocyte extracts. The isoprenoid metabolism appeared stage-dependent as shown by the increase of radiolabelled farnesyl pyrophosphate amount at the beginning of the schizogonic phase (30-36 hours). PMID- 2268348 TI - Differential proto-oncogene mRNA induction from rats treated with peroxisome proliferators. AB - After experimental treatment of rats with clofibrate or ciprofibrate, two peroxisomes proliferators with hypolipidemic activity, RNAs were prepared from liver, kidney, heart and brain; hybridization was done with DNA probes for c-myc and c-Ha-ras oncogenes and for cyanide insensitive Acyl CoA oxidase, a peroxisomal protein. c-myc mRNA is highly abundant in liver and at a lower extent in kidney, especially after treatment with ciprofibrate; clofibrate also allows a c-myc mRNA increase, but at a lower extent. c-Ha-ras, which is already expressed in all tested tissues from control animals, is stimulated by clofibrate and ciprofibrate treatments. Comparatively these compounds stimulate the cyanide insensitive Acyl CoA oxidase expression as well as they increase the somatic index of liver and kidney. From these experiments we suggest that hepatocarcinogenesis triggered by some hypolipidemic agents could be mediated by proto-oncogene mRNA level increase. PMID- 2268349 TI - DNA binding activity of casein kinase II. AB - Casein kinase II, an ubiquitous, oligomeric, messenger-independent protein kinase has previously been shown to concentrate in the nuclear compartment when cells are stimulated to proliferate. The present communication reports that purified mammalian CKII interacts with genomic DNA preparations in vitro. This interaction led to an apparent activation of the kinase, most likely explained by prevention of its aggregation and subsequent denaturation. Binding of CKII was optimum with double stranded DNA preparations; duplex lambda phage DNA exhibited at least two types of binding sites and the high affinity system (Kd approximately equal to 6 x 10(-13) M) represented a binding capacity of about 1 mol CKII per mol DNA. CKII DNA interaction was stimulated in the presence of a polyamine and inhibited by heparin. Blotting experiments disclosed that DNA binds CKII through its alpha subunit. These observations are in line with the hypothesis that casein kinase II may be examined as a component in the transduction of the mitogenic signal from the cell membrane to the nucleus, in response to growth factors. PMID- 2268350 TI - Human cellular src gene product: identification of the myristoylated pp60c-src and blockage of its myristoyl acylation with N-fatty acyl compounds resulted in the suppression of colony formation. AB - A p60K protein in human colon adenocarcinoma tumor cell lines was identified as a myristoylated pp60c-src by fluorography and radioimmunoprecipitation analysis. Prevention of the myristoylation of pp60c-src was determined with N-fatty acyl glycinal compounds. Of the compounds tested, N-myristoyl glycinal diethylacetal, N-lauroyl glycinal diethylacetal, N-myristoyl glycyl glycinal diethylacetal, and N-myristoyl-4-aminobutyl-aldehyde diethylacetal strongly blocked the myristoylation, but N-decanoyl glycinal diethylacetal and N-palmitoyl glycinal diethylacetal did not. The myristoyl blocking compounds depressed colony formation, cell proliferation, and specific localization to the plasma membrane of pp60c-src. The results taken together suggest that myristoylation of the c-src oncogene product may be very important for tumorigenicity of c-src gene expressed cells. PMID- 2268351 TI - Identification of pro-epidermal growth factor and high molecular weight epidermal growth factors in adult mouse urine. AB - By use of immunoblot analysis, we demonstrate the presence of a pro-Epidermal growth factor (EGF) with an approximate molecular weight of 165 kDa in adult mouse urine. In addition, urine contains four high molecular weight EGFs with approximate molecular weights of 116, 97, 66 and 56 kDa. The 165 kDa pro-EGF as well as the 66 and 56 kDa EGFs also are detectable in mouse kidney extract. Neither urine nor kidney contain the mature EGF of 6 kDa. The 165 kDa pro-EGF is the major product synthesized in renal tissue and secreted in urine. The finding of high molecular weight EGFs in urine suggests that part of pro-EGF secreted into urine undergoes partial proteolysis distal to its site of synthesis. PMID- 2268352 TI - Mechanisms of 4-hydroxytamoxifen anti-growth factor activity in breast cancer cells: alterations of growth factor receptor binding sites and tyrosine kinase activity. AB - We previously demonstrated that antiestrogen 4-hydroxytamoxifen (OH-Tam) blocks the mitogenic activity of growth factors in breast cancer. We now investigate this mechanism by evaluating how OH-Tam affects growth factor binding and receptor tyrosine kinase activity. We show here that OH-Tam has an opposite effect on epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) binding in estrogen receptor (ER) positive cells. A decrease in IGF-1 binding sites may explain the reduced IGF-I mitogenic effect, whereas an increase in high affinity EGF binding associated with a decrease in in vitro receptor autophosphorylation rather favors the possibility of an alteration in EGF receptor tyrosine kinase activity. We conclude that OH-Tam may prevent growth factor action in ER+ cells both by modulating the concentration of growth factor binding sites and by altering growth factor receptor functionality. PMID- 2268353 TI - Analysis of mixtures of closely related forms of bovine trypsin by electrospray ionization mass spectrometry: use of charge state distributions to resolve ions of the different forms. AB - Electrospray ionization mass spectrometry has been utilized for the analysis of bovine trypsin. Commercial active bovine trypsin is comprised of a mixture of three closely related different forms: beta-, alpha-, and psi-trypsin with similar molecular masses (23293, 23311, and 23329 mass units respectively). Peak broadening caused by the natural isotopic abundance of atoms in the protein molecules results in overlap of the ion peaks from the different trypsin forms. Therefore, accurate determination of the molecular masses of these trypsins in a mixture is not straightforward. However, because the trypsin isoforms have different number of basic groups and different higher order structures, the different forms acquire different numbers of charges. Therefore, ions from the different trypsins appear in different parts of the mass spectrum allowing accurate determination of their molecular masses. PMID- 2268354 TI - Substrate-dependent regulation of intracellular amino acid concentrations in cultured bovine aortic endothelial cells. AB - Amino acid deprivation induces adaptive changes in amino acid transport and the intracellular amino acid pool in cultured cells. In this study intracellular amino acid levels were determined in cultured bovine aortic endothelial cells (EC) deprived of L-arginine or total amino acids for 1, 3, 6 and 24 h. Amino acid concentrations were analyzed by reverse phase HPLC after precolumn derivatisation. Under normal culture conditions levels of L-arginine L citrulline, total essential and non-essential amino acids were 840 +/- 90 microM, 150 +/- 40 microM, 11.4 +/- 0.9 mM and 53.3 +/- 3.4 mM (n = 9), respectively. In EC deprived of L-arginine or all amino acids for 24 h L-arginine and L-citrulline levels were 200 microM and 50 microM, and 670 microM and 100 microM Deprivation of L-arginine or total amino acids induced rapid (1 h) decreases (30 - 50%) in the levels of other cationic (lysine, ornithine) and essential branched-chain (valine, isoleucine, leucine) and aromatic (phenylalanine, tryptophan) amino acids. L-glutamine was reduced markedly in EC deprived of total amino acids for 1 h - 6 h but actually increased 3-fold in EC deprived of L-arginine for 6 h or 24 h. Arginine deprivation resulted in a rapid decrease in the total intracellular amino acid pool, however concentrations were restored after 24 h. Increased amino acid transport and/or reduced protein synthesis may account for the restoration of amino acid levels in EC deprived of L-arginine. The sustained reduction in the free amino acid pool of EC deprived of all amino acids may reflect utilization of intracellular amino acids for protein synthesis. PMID- 2268355 TI - Hepoxilin A3 blocks the release of norepinephrine from rat hippocampal slices. AB - Hepoxilin A3 was previously shown to display neuromodulatory actions on rat hippocampal CA1 neurons, with hyperpolarization of the membrane potential, an increase in the amplitude and duration of the post-spike train after hyperpolarization and an increase in the inhibitory post synaptic potential. The present report describes new biochemical evidence of a presynaptic action of hepoxilin A3 in rat hippocampal slices prelabeled with [3H]-norepinephrine. Hepoxilin A3 on its own had a marginal effect on the release of label, but blocked release which was induced by 4-aminopyridine (4-AP). Prostaglandin E2 also behaved in a similar way. These results demonstrate that hepoxilins modulate neurotransmission in the mammalian CNS through both pre- and postsynaptic actions. PMID- 2268356 TI - Transcortin does not restrict the transmembrane transfer of cortisol. AB - We have studied the specific binding of both free and transcortin-bound cortisol to the microvesicles derived from the brush border of the plasma membrane of human placental syncytiotrophoblast. Kinetics of the steroid binding to these microvesicles was found to be independent on cortisol being complexed with transcortin. Both cortisol and transcortin were accumulated in the inner space of the microvesicles. This suggests that transcortin-cortisol complex penetrates the plasma membrane and the transcortin-bound steroid can thus enter syncytiotrophoblast and exert its hormonal effects on this tissue. PMID- 2268358 TI - Superactive insulins. AB - The substitution of aspartic acid for the naturally-occurring histidine residue in position B10 in human insulin results in an insulin analogue which displays an in vitro potency 4- to 5-fold greater than the parent compound. This substitution has been introduced into six insulin analogues which, before modification, display potencies ranging from less than 0.01-fold to 3-fold relative to natural insulin. In each case, the resulting aspartic acid-substituted analogue is substantially more potent than the parent compound. Thus, it is now possible to prepare "tailor-made" insulins with enhanced potency. PMID- 2268359 TI - Interleukin 1 potentiates agonist-induced secretion of beta-endorphin in anterior pituitary cells. AB - Interleukin 1 (IL-1) has been shown to potentiate the release of beta-endorphin induced by secretagogues, including corticotropin releasing factor (CRF) and phorbol ester (TPA), in the mouse AtT-20 pituitary tumor cell line (Fagarasan et al., PNAS, 1989, 86, 2070-2073). In cultured rat anterior pituitary cells, pretreatment with IL-1 caused only a small increase in beta-endorphin release but significantly potentiated CRF-and vasopressin-stimulated beta-endorphin secretion. Vasopressin stimulates the secretion of beta-endorphin in normal pituitary cells but not in AtT-20 cells. However, treatment of AtT-20 cells with IL-1 induced the expression of vasopressin-mediated beta-endorphin release; this effect of IL-1 was reduced after depletion of protein kinase C by prolonged treatment with TPA. The enhancement of CRF-stimulated beta-endorphin release by IL-1 was also reduced in AtT-20 cells after depletion of protein kinase C, and after treatment with staurosporine. These findings indicate that treatment with IL-1 amplifies receptor-mediated responses to the major physiological secretagogues in normal corticotrophs, and initiates a secretory response to vasopressin in AtT-20 cells. PMID- 2268357 TI - Effect of K252a, a protein kinase inhibitor, on the proliferation of vascular smooth muscle cells. AB - In the growth arrested cultures of bovine carotid smooth muscle, K252a (10 - 100 ng/ml), a protein kinase inhibitor with wide spectrum suppressed the cell proliferation induced by TPA and increase of serum. K252a was more potent in the antiproliferative activity than H7, a C-kinase-specific inhibitor, but less than staurosporine, another wide-spectrum protein kinase inhibitor. Since C-kinase plays an important role in the signal transduction leading to the cell proliferation and K252a inhibits C-kinase in vitro, the antiproliferative effect of K252a to carotid smooth muscle cells is likely to be exerted through c-kinase dependent pathway. PMID- 2268360 TI - Characterization of a new lignin peroxidase gene (GLG6) from Phanerochaete chrysosporium. AB - Sequence analysis of a new lignin peroxidase (LIP) gene, GLG6, from P. chrysosporium showed that it encodes a mature LIP protein with a predicted Mr of 36,454. A 28 aa signal peptide precedes the mature protein. The coding region of GLG6 is interrupted by nine introns ranging in size from 50-57 bp. GLG6 encoded LIP has 72%, 88% and 82% homology, respectively, to the LIP isozymes H2, H3, and H10. Comparison of the N-terminal sequence of GLG6-encoded LIP to that of the LIP proteins H2, H8, H10 also showed that the former is relatively less related to the H2 protein than it is to the H8 and H10 proteins. Expression of GLG6, similar to the other LIP genes, occurs only during secondary metabolism. PMID- 2268361 TI - Formation of a cytotoxic metabolite from gentamicin by liver. PMID- 2268362 TI - Aminoglycoside-induced renal phospholipidosis and nephrotoxicity. PMID- 2268363 TI - Adrenal steroid influences on the survival of hippocampal neurons. PMID- 2268364 TI - Mechanisms of stabilization of biomembranes by alpha-tocopherol. The role of the hydrocarbon chain in the inhibition of lipid peroxidation. AB - The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C1, C6, C11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alpha-tocopherol homologues decreased in the order: C1 greater than C6 greater than C11 greater than alpha-tocopherol (C16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C1 with membranes was less efficient than that of longer-chain homologues (C6, C11, C16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C11 greater than C6 greater than C1; (iii) all alpha-tocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C1, exhibited a high transbilayer mobility whereas the long-chain one, C16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C1-acetate exhibited very low lipid peroxidation inhibition. PMID- 2268365 TI - Biochemical alterations in skeletal muscle induced by 2,4-dichlorophenoxyacetic butyl ester during chick embryonic development. AB - 2,4-Dichlorophenoxyacetic butyl ester (2,4-D b.e.) (3.1 mg/egg) was applied on fertile hen eggs before starting the incubation. Chicks hatched from treated eggs showed motor dysfunctions, postural troubles and edematous muscles. The electromyography revealed muscular weakness, prolonged motor distal latency, and myotonia. The biochemical composition of leg and complexus muscles from 1-day-old chicks was determined. A significant diminution (24%) in the glycogen level of leg muscles was produced by the treatment. There was a small increase (15%) in sarcoplasmic proteins from leg muscles and an increase of a 20 kD protein in the myofibrillar proteins from complexus muscles. Even though total lipid content was not changed, 2,4-D b.e. treatment produced a diminution of sterol esters (20%) and phosphatidylcholine (11%) and an increase of phosphatidylserine (61%), triglycerides (37%) and free fatty acids (FFA) (448%) in leg muscles. Increases of phosphatidylethanolamine (16%), sterols (58%) and FFA (267%) were detected in complexus muscles. A remarkable increase (700-1500%) of unsaturated FFA, e.g. oleic, linoleic and arachidonic acids, was observed. Considering the avian embryo lipid metabolism, it is proposed that FFA and triglycerides were accumulated because they could not be metabolized in the mitochondria. Since FFA are potent cytotoxic compounds, their increase may be a key factor in the 2,4-D b.e. toxic action in muscle and other tissues during embryonic development. PMID- 2268366 TI - Effect of epinephrine on ethanol metabolism by isolated rat hepatocytes. AB - The effect of epinephrine on ethanol metabolism was determined in isolated rat hepatocytes. Epinephrine (10 microM) enhanced an initial rapid rate of ethanol elimination observed in the first 5 min. Thereafter, between 5 and 90 min, the rate of ethanol elimination was slower and not affected by epinephrine. Epinephrine resulted in higher acetaldehyde concentrations at 2 min, but not thereafter. Acetaldehyde production in the presence and absence of epinephrine was inhibited by 4-methylpyrazole, by a low free extracellular calcium concentration, and by the alpha 1-adrenergic blocker prazosin. Ethanol alone and epinephrine alone increased oxygen consumption, but the effects were not additive. The ethanol-induced decreases in the cytosolic NAD-/NADH and NADP++NADPH ratios and in the mitochondrial NAD+/NADH ratio were delayed by the presence of epinephrine. An accelerated initial alcohol dehydrogenase activity sufficient to account for the rapid initial rate of ethanol elimination shown with epinephrine was demonstrated by coupling ethanol oxidation with lactaldehyde reduction, a system which increases the rate of dissociation of NADH from the enzyme and its oxidation back to NAD+. The findings in this study indicate that an increased reoxidation of NADH during ethanol oxidation by alcohol dehydrogenase is the basis for the rapid transient increase in ethanol elimination produced by epinephrine. PMID- 2268367 TI - Inhibition by manoalide of fMLP-stimulated elastase release from human neutrophils. AB - Incubation of human polymorphonuclear leukocytes (PMNLs) with the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) resulted in a concentration-dependent release of the neutral protease elastase. This response was inhibited by pretreatment of the PMNLs with manoalide (IC50 approximately 0.08 microM). To understand the mechanism of this inhibition, we examined the effect of manoalide on the signal-transduction pathway believed to mediate fMLP stimulation. We observed in fura-2 loaded cells that pretreatment with manoalide blocked fMLP-induced increases in cytosolic free-calcium (IC50 approximately 0.15 microM). However, manoalide had no effect on inositol 1,4,5-trisphosphate (IP3) production at concentrations which completely inhibited the Ca2+ signal. Furthermore, manoalide was approximately 50-fold less potent as an inhibitor of phospholipase C activity in membrane preparations of PMNLs than as an inhibitor of calcium mobilization in whole cells. These data indicate that manoalide can block stimulation of human PMNLs through inhibition of Ca2+ mobilization, but that this occurs at a site beyond phospholipase C activation and inositol phosphate turnover. PMID- 2268368 TI - Regulation of ovarian carbonyl reductase mediated by estrogen receptor in immature rats. AB - In the present study, the enhancing effect of synthetic estrogen on ovarian carbonyl reductase, a new prostaglandin (PG)-metabolizing enzyme, was investigated, and the antagonistic effect of antiestrogen on this enhancement was examined in immature rats. Ovarian carbonyl reductase activity towards 13,14 dihydro-15-keto-PGF2 alpha (15KD-PGF2 alpha), 4-benzoylpyridine (4BP) and menadione was determined photometrically and radiochemically, and quantitation of ovarian carbonyl reductase content was performed by Western blot analysis. Diethylstilbestrol (DES) and hexestrol (HX) enhanced the increasing effect of human chorionic gonadotropin (hCG) on ovarian carbonyl reductase activity and content when these synthetic estrogens (0.2 mg/kg) were administered for 3 days from 26 days of age, before hCG treatment. On the other hand, tamoxifen, which inhibits the binding of estradiol to the estrogen receptor, significantly prevented estradiol (E2) from enhancing the effect of hCG on ovarian carbonyl reductase. Furthermore, the ovarian carbonyl reductase activities towards the three substrates correlated well with the ovarian carbonyl reductase content. These results indicate that ovarian carbonyl reductase in immature rats may be regulated by a specific increase in the ovarian response to luteinizing hormone mediated by estrogen receptor. PMID- 2268369 TI - Immunochemical detection of human liver cytochrome P450 forms related to phenobarbital-inducible forms in the mouse. AB - Polyclonal antibodies generated to four distinct mouse liver phenobarbital inducible cytochrome P450 isoforms were used to analyse related forms in human liver. N-terminal sequence analysis and biochemical properties of the P450s used as antigens suggest that they belong to P450 subfamilies IIB (P450PBI), IA (P450PBII), IIC (P450PBIII) and IIA (P450Coh). In immunoblot analysis, anti P450PBII detected a single protein presumed to be P450IA2 in all the human livers tested. No proteins corresponding with P450IA1 could be detected. Anti-PBIII and anti-P450Coh antibodies each detected one band (54 and 48 kDa, respectively) in the liver samples. No bands were revealed by anti-P450PBI antibody. Protein dot immunobinding analysis showed that P450s immunodetectable by anti-P450PBII, anti P450PBIII and anti-P450Coh antibodies are expressed in human liver (range 9 to 69 pmol P450/mg protein). In immunoinhibition experiments the activity of 7 ethoxyresorutin O-deethylase (EROD) was blocked up to 90% by the anti-P450PBII antibody. Aryl hydrocarbon hydroxylase (AHH) was inhibited only by anti P450PBIII, and coumarin 7-hydroxylase (COH) only by anti-P450Coh antibody. Testosterone hydroxylations in positions 6 beta, 7 alpha, 15 alpha and 16 alpha were not affected significantly by any of the antibodies. These data suggest that the human liver P450IA2 is responsible for most of the elevated EROD activity, P450s in the IIC subfamily for constitutive AHH and P450s in the IIA subfamily for all of COH activity. PMID- 2268370 TI - Changes in the biliary excretion of organic anions following exhaustive exercise in rats. AB - The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked reduction of glycogen concentration in the liver (-72%). When bromosulphthalein was administered i.v., its maximal biliary excretion (Tm) was significantly reduced (-30%), and plasma and liver concentrations of the dye were increased (+31% and +56%, respectively). The decrease corresponded both to the excretion of the conjugated and unconjugated dye (-30% and -33%, respectively). Cytosolic glutathione S-transferase activity in the liver was not affected by exercise, but there was a significant reduction in the hepatic concentration of glutathione (-50%). The Tm of dibromosulphthalein was also significantly reduced (-36%) and its plasma and liver concentrations increased (+67% and +33%, respectively) in exercised rats. The results suggest that, in addition to the direct effect of liver glutathione depletion, other factors must be involved in the impairment of the biliary excretion of organic anions caused by exercise. PMID- 2268371 TI - The isoenzyme pattern of cytochrome P450 in rat hepatocytes in primary culture, comparing different enzyme activities in microsomal incubations and in intact monolayers. AB - Changes in the isoenzyme pattern of cytochrome P450 during culture were investigated in primary cultures of rat hepatocytes, measuring specific enzyme activities in microsomes prepared from cultured cells as well as in intact monolayers. Assays of 7-ethoxyresorufin O-deethylation (EROD), 7-pentoxyresorufin O-depentylation (PROD), aniline 4-hydroxylation (AH) and the specific regioselective hydroxylation of testosterone were used as representatives of the activities of seven isoenzymes of cytochrome P450. The isoenzyme profile expressed as catalytic activities was qualitatively and quantitatively similar in microsomes obtained from freshly isolated hepatocytes in comparison with microsomes obtained from whole livers of untreated rats. There was a relatively high activity in EROD, AH and the oxidation of testosterone at the 7 alpha, 2 alpha, 6 beta, 16 alpha and 17 sites (androstenedione). During culture, these microsomal enzyme activities declined at a similar rate to ca. 50% of the activities of microsomes prepared from freshly isolated hepatocytes after 24 hr and to 15% after 96 hr. The overall decline of cytochrome P450-dependent activities during culture was not accompanied with gross changes in catalytic profile. Determining the same drug-metabolizing activities directly in intact hepatocyte monolayers revealed a much higher metabolic rate for all measured P450 dependent activities. The profile of the catalytic activities was essentially the same as measured in microsomes prepared from cultured hepatocytes. The relatively low activity towards the 7 alpha site of testosterone measured in intact hepatocytes, however, remained constant during culture. Determination of enzyme activities directly in intact hepatocytes is a convenient way of studying changes in monooxygenase activities of different P450 isoenzymes in vitro. PMID- 2268372 TI - Interaction of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, an inhibitor of plasma protein binding in uraemia, with human albumin. AB - The furan dicarboxylic acid 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5 propyl FPA) accumulates in uraemic plasma and is a potent inhibitor of the binding of other anionic ligands to albumin. The interaction of 5-propyl FPA with human albumin has been investigated by equilibrium dialysis at 37 degrees and pH 7.4. Analysis of the binding data on the basis of a two-site model gave binding parameters of n1 = 0.6 and K1 = 4.8 x 10(6) M-1 for the primary binding site. 5 Propyl FPA binding was observed to decrease as the pH was raised from 6.4 to 8.3 which emphasizes the need for pH control of whole plasma or serum. Temperature, however, had little effect on binding as assessed by equilibrium dialysis at 10 degrees, 25 degrees and 37 degrees. The high affinity of 5-propyl FPA for albumin explains its retention in uraemic plasma, its potency as a binding inhibitor and points to active tubular secretion as the mechanism by which it is normally excreted by the kidney. PMID- 2268373 TI - Injection of sulbutiamine induces an increase in thiamine triphosphate in rat tissues. PMID- 2268374 TI - Monoamine oxidase substrates in Parkinson's disease. PMID- 2268375 TI - Protection against iron-induced uroporphyria in C57BL/10ScSn mice by the peroxisome proliferator nafenopin. PMID- 2268377 TI - Use of a spread sheet to calculate the current-density distribution produced in human and rat models by low-frequency electric fields. AB - The current-density distribution produced inside irregularly shaped, homogeneous human and rat models by low-frequency electric fields is obtained by a two-stage finite-difference procedure. In the first stage the model is assumed to be equipotential. Laplace's equation is solved by iteration in the external region to obtain the capacitive-current densities at the model's surface elements. These values then provide the boundary conditions for the second-stage relaxation solution, which yields the internal current-density distribution. Calculations were performed with the Excel spread-sheet program on a Macintosh-II microcomputer. A spread sheet is a two-dimensional array of cells. Each cell of the sheet can represent a square element of space. Equations relating the values of the cells can represent the relationships between the potentials in the corresponding spatial elements. Extension to three dimensions is readily made. Good agreement was obtained with current densities measured on human models with both, one, or no legs grounded and on rat models in four different grounding configurations. The results also compared well with predictions of more sophisticated numerical analyses. Spread sheets can provide an inexpensive and relatively simple means to perform good, approximate dosimetric calculations on irregularly shaped objects. PMID- 2268376 TI - Effect of negative air ions on morphine-induced changes in the latency of the tail-flick reflex. AB - Adult male Long-Evans rats were exposed to negatively charged air ions at high concentrations (7 x 10(5)/cm3) for six days. Sham-exposed rats were treated identically except that the source of ions was not activated. At the end of the exposure, the latency of the tail-flick reflex was measured in each rat before and 30 and 60 min after an injection of morphine sulphate. The tail-flick reflex was initiated by thermal stimulation. Two heat settings were employed, the lower considered to impart a submaximal and the higher a maximal thermal stimulus. Three morphine doses were tested: 0.5, 1.0, and 1.5 mg/kg. Statistically significant differences between ion-exposed and sham-exposed rats were observed in tail-flick latencies 30 min after the administration of the two lower doses, but not after the highest dose of morphine sulphate. These differences were found at both intensities of thermal stimulation. Tail-flick latencies measured in each group prior to morphine injection were not affected by negative-ion exposure. The data indicate that exposure of rats to negative air ions tends to inhibit the action of morphine on the latency of the tail-flick reflex at morphine doses below 1.0 mg/kg. PMID- 2268378 TI - Exposure of mammalian cells to 60-Hz magnetic or electric fields: analysis of DNA repair of induced, single-strand breaks. AB - DNA damage was induced in isolated human peripheral lymphocytes by exposure at 5 Gy to 60Co radiation. Cells were permitted to repair the DNA damage while exposed to 60-Hz fields or while sham-exposed. Exposed cells were subjected to magnetic (B) or electric (E) fields, alone or in combination, throughout their allotted repair time. Repair was stopped at specific times, and the cells were immediately lysed and then analyzed for the presence of DNA single-strand breaks (SSB) by the alkaline-elution technique. Fifty to 75 percent of the induced SSB were repaired 20 min after exposure, and most of the remaining damage was repaired after 180 min. Cells were exposed to a 60-Hz ac B field of 1 mT; an E field of 1 or 20 V/m; or combined E and B fields of 0.2 V/m and 0.05 mT, 6 V/m and 0.6 mT, or 20 V/m and 1 mT. None of the exposures was observed to affect significantly the repair of DNA SSB. PMID- 2268379 TI - Electric fields induced by low frequency magnetic fields in inhomogeneous biological structures that are surrounded by an electric insulator. AB - Electric fields induced by low-frequency magnetic fields into inhomogeneous structures, which have electric conductivities and dielectric permittivities of typical biological substances, are evaluated. Closed-form approximate and numerical solutions are obtained for nonconcentric cylinders with different electric properties (such as bone embedded in muscle), which are surrounded by a good electrical insulator (such as air). It is shown that even a single inhomogeneity in an otherwise homogenous cylinder, which is exposed to a uniform, axially directed magnetic field, can lead to substantial deviations from the direction and distribution of the induced electric field that would exist in the homogenous cylinder. Thus the induced field is not everywhere circumferential, nor does it magnitude at all angular positions increase linearly with the radial distance. Radially and circumferentially directed field components depend on size, electrical properties, and eccentricity of the inhomogeneities. Equations as well as graphical presentations are given that describe the induced fields when the enclosed inhomogeneities consist either of eccentrically located single cylinders or pairs of coaxial cylinders with different electrical conductivities or dielectric permittivities. PMID- 2268380 TI - Optimal experimental design for in vitro studies with ELF magnetic fields. AB - An experimental arrangement is described that maximized the dosimetric information that can be obtained during in vitro studies with ELF magnetic fields. The arrangement enables researchers to distinguish between a purely magnetic-field effect and one that also involves the electric fields and currents induced by the magnetic field. PMID- 2268381 TI - Brown-colored deposits on hair of female rats chronically exposed to 60-Hz electric fields. AB - An increased incidence and severity of a brownish coloration of hair has been observed around the nose and on the ears of female rats that were chronically exposed to 60-Hz electric fields. Microscopic examination of the colored areas revealed a red-brown globular deposit on hair shafts in affected areas without signs of physical injury. PMID- 2268382 TI - Acute parenteral neurotoxicity of domoic acid in cynomolgus monkeys (M. fascicularis) AB - To study the CNS effects of domoic acid (D.A.), 6 adult Cynomolgus monkeys (M. fascicularis) were dosed intraperitoneally (4 mg/kg) or intravenously (0.025-0.5 mg/kg) with D.A. obtained from cultured mussels contaminated with this neurotoxin. Clinical signs of neurotoxicity were preceded by a short presymptomatic period (2-3 min) and an even shorter prodromal period (0.5-1 min). The symptomatic period proper was characterized by persistent chewing with frothing, varying degrees of gagging, and vomit. Monkeys in the higher dose regimen exhibited additional signs including abnormal head and body positions, rigidity of movements and loss of balance, and tremors. The duration of the symptomatic period was dose dependent. Excitotoxic lesions consisting of vacuolation of the neuropil, astrocytic swelling, and neuronal shrinkage and hyperchromasia were detected in the area postrema, the hypothalamus, the hippocampus, and the inner layers of the retina in monkeys given D.A. at 0.5 mg/kg intravenously and 4 mg/kg intraperitoneally. It was concluded that D.A., administered intravenously, is neuroexcitatory and a powerful emetic at doses of 0.025 to 0.2 mg/kg. At higher doses (0.5 mg/kg intravenously and 4 mg/kg intraperitoneally), D.A. is strongly excitotoxic. PMID- 2268383 TI - Lower limb amputation in three Australian states. AB - A study has been made of lower limb amputation statistics from morbidity data from the State Health Departments in New South Wales, Queensland, and Western Australia. The incidence of lower limb amputation in these three States was 22.6 in 1981, 22.5 in 1983, and 23.6 in 1984. Incidence was lowest in New South Wales and highest in Western Australia. Below-knee amputation was more common than above-knee except in Western Australia in the years 1981 and 1983. Males had slightly more amputations than females. Incidence increased steadily with age, rising rapidly after 55 years. Vascular disease was the most common cause of major amputation. Of malignancies, skin cancers, both malignant melanoma and other forms, were causes of major and minor amputations in addition to bone malignancies. These three Australian States have a lower incidence of amputation than the United Kingdom or Finland. PMID- 2268385 TI - Joint meeting SEP-SEPCR. London, September 9-14, 1990. Abstracts. PMID- 2268384 TI - mRNA coding for oxytocin is present in axons of the hypothalamo-neurohypophysial tract. AB - Neuronal mRNA is thought to be restricted to perikaryal and dendritic compartments containing rough endoplasmic reticulum. We have used both in situ hybridization and DNA polymerase chain reaction methods to determine the precise intracellular distribution of oxytocin mRNA. Using light- and electron microscopic detection of in situ hybridization with 5'-bromo-2'-deoxyuridine labeled oligonucleotide probes, we found oxytocin mRNA in axons and Herring bodies in the lateral and ventral hypothalamus, the median eminence, and the posterior lobe of the pituitary in postpartum lactating rats. Southern blot analysis of the amplification products confirmed the presence of oxytocin mRNA in all three tissue samples. The present findings indicate that oxytocin mRNA can be transported axonally. Such transport could reflect an adventitious compartmentalization or a functional storage in Herring bodies for subsequent secretion. PMID- 2268386 TI - Computer-aided diagnosis of breast aspirates via expert systems. AB - Two computer-driven expert systems trained to correctly diagnose 369 fine needle aspirates of the breast on the basis of nine cytologic descriptive parameters were tested on 70 newly obtained aspirates (57 benign and 13 malignant). The system generated by multisurface pattern separation misclassified one malignant test sample (i.e., one false negative) while the system generated by a connectionist algorithm (neural network) misclassified two benign test samples (i.e., two false positives). A decision tree misclassified three of the benign test samples (i.e., three false positives). These expert systems aid in the cytologic diagnosis of breast aspirates and can serve as models for other applications. PMID- 2268387 TI - Quantitative analysis of cytoskeletal proteins throughout the cell cycle of the MRC-5 fibroblastic cell line. AB - Fluorescent dyes were used to stain actin, vimentin, tubulin and DNA in the same MRC-5 fibroblastic cells. Cytofluorometry and image analysis were then used to quantitatively evaluate the F actin, vimentin and tubulin content throughout the cell cycle. The results showed that different cells can have the same DNA content while their cytoskeletal protein content is variable. The data also showed that cytoskeletal protein content variations exist throughout the cell cycle of the fibroblastic cell line. The F actin content increased during the cell cycle from G1 to G2 phases and decreased in M phase. The amount of tubulin in the G2 was about twice as much as that in the G1 phase, before decreasing in the M phase; there was a threshold of tubulin content for G2 cells entering S phase. PMID- 2268388 TI - Interrelation of formalin fixation, chromatin compactness and DNA values as measured by flow and image cytometry. AB - The severity and consistency of the effect of formalin fixation on the quantitation of DNA by flow cytometry (FCM) and image cytometry (ICM) were studied. As compared to ethanol, formalin fixation substantially decreased the propidium iodide fluorescence from mouse hepatocyte nuclei analyzed by FCM; it was also associated with an altered 4n-to-2n signal ratio and with false aneuploid peaks by FCM, but not by ICM (microspectrophotometry). ICM, on the other hand, suffered from a dependence of the DNA signal on nuclear size, which was not seen with FCM. The DNA signal variation was related to variations in the chromatin state, as shown by differences between monocytes and lymphocytes, and between RAJI cells fixed under various ionic strengths. The dependence of the DNA signal on the chromatin state indicates a need for caution in interpreting aneuploidy in formalin-fixed cells. For FCM, pseudoaneuploidy appears avoidable by using a Feulgen fluorescence staining technique. New imaging modes may be necessary to solve the problem of cell size dependence for ICM DNA determination. PMID- 2268389 TI - Information, discrimination and divergence in cytology. I. Theoretical aspects and definitions. AB - The results of medical tests update the probability of diagnosis (diagnosability) of a patient from the population prevalence of a disease. This paper demonstrates a method of combining several mutually dependent tests as the sum of log odds ratios, and of separating the log odd ratios of the test results and those of prevalences. Extending Kullback's discriminant function between two states to m states (m greater than or equal to 2), it is shown that the information of a test can be measured by discrimination and divergence, which are well-defined measures in information theory and test theory. The performance of diagnostic cytology can then be compared to the results of histopathologic diagnoses or to a peer reviewed consensus without the use of arbitrarily given scores or without unfounded assumptions about underlying continuous variables. They can also provide a way to optimize the categorization (classification) of Papanicolaou smears and a means of quality control for morphologic tests. These methods can be used to evaluate the performances of cytology laboratories that use two classifications consisting of different numbers of categories (classes) and states. PMID- 2268390 TI - Heterogeneity of DNA distribution pattern in colorectal carcinoma. A microspectrophotometric study of fine needle aspirates. AB - For 50 consecutive patients with colorectal carcinoma, the nuclear DNA content in four separate fine needle aspiration samples taken from the resected tumors was analyzed using single-cell Feulgen cytometry. The DNA distribution patterns were divided into four classes according to their degree of euploidy/aneuploidy. Twenty tumors (40%) displayed a similar DNA pattern in all four samples while 30 tumors (60%) were heterogeneous, with a different DNA pattern within one or more of the four samples. None of the tumors were homogeneously diploid. These results illustrate the importance of multiple biopsy samples in the evaluation of the DNA pattern in colorectal tumors. PMID- 2268391 TI - Comparison of DNA ploidy and nuclear size, shape and chromatin irregularity in tissue sections and smears of prostatic carcinoma. AB - Image analysis measurements of nuclear size, shape, texture and DNA ploidy were compared in smears versus the corresponding 4-microns tissue sections, both prepared from radical prostatectomy specimens obtained from resections for prostatic cancer. Thirty-nine cases (78%) showed concordant DNA histograms between the smear and the tissue section. In six cases (12%), both preparations were nondiploid, but a tetraploid population was also present in one, but not both, of the preparations. In five cases (10%), there was a major discordance between the smear and the tissue section, with one preparation diploid and the other nondiploid. One source of discrepancy between the smear and tissue histograms was the overlapping of larger nuclei in tissue sections, which often precluded the analysis of the most atypical cells. Some tissue histograms were difficult to interpret due to wide coefficients of variation, irregular peaks and some shift from 2n in the diploid peaks. The best morphometric correlation (0.78) between the smears and the tissue sections was for the modal nuclear shape. Nuclear size and texture measurements showed poorer correlations. These findings suggest that cytologic preparations of prostatic carcinoma should be preferred for image analysis. PMID- 2268393 TI - [Distribution of medical bivalve in the tidal zone at sand beach of Dalus Island]. PMID- 2268392 TI - [Herbalogical studies on bulbus Lilii]. AB - A textual research has been carried out herbalogically on Bulbus Lilii, along with a pharmacological study and resources investigation. Lanceleaf Lily is regarded as the first choice of the drug. PMID- 2268394 TI - [Pharmacognostical studies on flos Houpo produced in Yunnan Province]. PMID- 2268395 TI - [Content of histoamine in processed Phytolacca americana L]. AB - The contents of histamine in processed Phytolacca americana has been determined by colorimetry. The result shows that the contents tend to decrease by 23.3% when the herb is shredded, but get a bit higher again when fried with vinegar. The method may be useful in the quality control of the herb. PMID- 2268396 TI - [Determination of soluble mercury contents in Chinese traditional patent medicines for children]. AB - Soluble mercury contents in Baochi San, Xiaoer Zhibon Ding and Xiaoer Baishou Dan have been determined using dithizone method. This method has the advantages of short digestion time, clear digestion end point, simple operation and reproducible results. The recovery rate ranges from 98.4 to 103%. The data obtained can be used as a reference for controlling soluble mercury contents in Chinese traditional patent medicines containing cinnabar. PMID- 2268397 TI - [Determination of icarim in luohan jindan oral liquid by thin-layer chromatography]. AB - The oral liquid of Luohan Jindan is composed of fifteen traditional Chinese drugs. Icariin in the oral liquid has been successfully separated and determined by using column partition chromatography-TLC-UV spectrum method. Interferences from other components in the liquid can be removed by this method, which is simple, precise, accurate, and also useful in the quality control of Herba Epimedii preparations. PMID- 2268398 TI - [Chemical studies on the constituents of Daphne koreane Nakai]. AB - In this paper three compounds isolated from Daphne koreane are described. Their structures have been identified as beta-sitosterol, naringenin and 7,8 dimethoxycoumarin on the basis of spectral data and chemical reactions. PMID- 2268399 TI - [Antimutagenicity screening of water extracts from 102 kinds of Chinese medicinal herbs]. AB - Our observation shows that out of 102 kinds of Chinese medicinal herbs tested, 17 have remarkable antimutagenic effect on the mutation induced by aflatoxin B1, in Ames test. Among the 17 herbs Glycyrrhiza uralensis, Bupleurm chinense, Portulaca grandiflora and Cnidium monnieri have been found in other tests to be effective against mutagenesis induced by cyclophosphamide in mice. PMID- 2268400 TI - [Pharmacological effects of yinqiao jiedu oral liquid]. PMID- 2268401 TI - [Differentiation of human leukemia cell (HL-60) induced by Sophora flavescens Ait. decoction]. PMID- 2268402 TI - [A review on studies of antioxidation of Chinese materia medica]. PMID- 2268403 TI - Two-dimensional 1H and 31P NMR spectra and restrained molecular dynamics structure of an oligodeoxyribonucleotide duplex refined via a hybrid relaxation matrix procedure. AB - Assignment of the 1H and 31P resonances of a decamer DNA duplex, d(CGCTTAAGCG)2 was determined by two-dimensional COSY, NOESY and 1H-31P Pure Absorption phase Constant time (PAC) heteronuclear correlation spectroscopy. The solution structure of the decamer was calculated by an iterative hybrid relaxation matrix method combined with NOESY-distance restrained molecular dynamics. The distances from the 2D NOESY spectra were calculated from the relaxation rate matrix which were evaluated from a hybrid NOESY volume matrix comprising elements from the experiment and those calculated from an initial structure. The hybrid matrix derived distances were then used in a restrained molecular dynamics procedure to obtain a new structure that better approximates the NOESY spectra. The resulting partially refined structure was then used to calculate an improved theoretical NOESY volume matrix which is once again merged with the experimental matrix until refinement is complete. JH3'-P coupling constants for each of the phosphates of the decamer were obtained from 1H-31P J-resolved selective proton flip 2D spectra. By using a modified Karplus relationship the C4'-C3'-O3'-P torsional angles (epsilon) were obtained. Comparison of the 31P chemical shifts and JH3'-P coupling constants of this sequence has allowed a greater insight into the various factors responsible for 31P chemical shift variations in oligonucleotides. It also provides an important probe of the sequence-dependent structural variation of the deoxyribose phosphate backbone of DNA in solution. These correlations are consistent with the hypothesis that changes in local helical structure perturb the deoxyribose phosphate backbone. The variation of the 31P chemical shift, and the degree of this variation from one base step to the next is proposed as a potential probe of local helical conformation within the DNA double helix. The pattern of calculated epsilon and zeta torsional angles from the restrained molecular dynamics refinement agrees quite well with the measured JH3'-P coupling constants. Thus, the local helical parameters determine the length of the phosphodiester backbone which in turn constrains the phosphate in various allowed conformations. PMID- 2268404 TI - The infrared and Raman spectra of the duplex of d(GGTATACC) in the crystal show bands due to both the A-form and the B-form of DNA. AB - The deoxyoligonucleotide, d(GGTATACC), forms a duplex structure that crystallizes in the DNA A form. This has been shown by both X-ray diffraction studies and Raman spectroscopy (1,2). The presence of the DNA B form has been reported using diffuse X-ray scattering from a crystal of the closely related sequence d(GGBrUABrUACC)(3). In this paper the infrared spectrum of the d(GGTATACC) crystal is presented and curve resolution of both the Raman and IR spectra have been carried out. The percentage of A and B forms have been estimated. The %B form in the crystal has been estimated from the IR spectra to be about 15% and from Raman to be about 20%. Moreover the IR spectrum of the A conformation in the crystal is slightly different from the IR spectrum of the A conformation in polynucleotide fibers in particular in the region of the phosphate stretching vibrations and of the in-plane double bond vibrations of the bases. We show that it is feasible to obtain IR as well as Raman spectra of small crystals of oligonucleotides and that this is a good method of identifying all of the different conformations that may be in the crystal. PMID- 2268405 TI - Interaction of deoxyguanylic acid with alkaline earth metal ions. Evidence for the deoxyribose C3'-endo/anti, O4'-endo/anti and C2'-endo/anti conformational transitions. AB - The interaction of 2'-deoxyguanosine-5'-monophosphoric acid (H2-dGMP) with the alkaline earth metal ions has been investigated in aqueous solution at neutral pH. The solid salts of the type Mg-dGMP.5H2O Ca-dGMP.6H2O, Sr-dGMP.7H2O and Ba dGMP.7H2O were isolated and characterized by FT-IR, proton-NMR and X-ray powder diffraction measurements. Two types of metal-nucleotide interactions have been identified: (a) the indirect metal-base and the direct metal-phosphate bindings (outer- and inner-sphere interaction), for the Mg(II) and Sr(II) ions and (b) the direct metal-base and direct metal-phosphate bindings (inner-sphere interaction), for the Ca(II) and Ba(II) ions. In aqueous solution, a dynamic equilibrium of the type base-metal-H2O. . .PO3 in equilibrium base. . .H2O-metal-PO3 is present. The deoxyribose moiety exhibits C3'-endo/anti conformation, in the Mg(II)-, Ca(II)-, Sr(II)- and Ba(II)-dGMP salts. PMID- 2268407 TI - General nearest neighbor preferences in G/C oligomers interrupted by A/T: correlation with DNA structure. AB - The frequencies of occurrence of the 5' and 3' nearest neighbor doublets of oligonucleotides containing (G/C) and (A/T) blocks show strong trends. Specifically, the following trends are observed. Given a (G/C)n (A/T)m oligomer (where G/C)n indicates a sequence of length n composed solely of Gs and/or Cs and (A/T)m is a sequence of length m composed solely of As and/or Ts, and n = 3,2,1; m = 1,2,3) and a (G/mC)2 doublet, (G/C)n (A/T)m (G/C)2 greater than (G/C)n + 2 (A/T)m. That is the (G/C)2 doublet is preferentially located 3' of the oligomer, enclosing the (A/T)m stretch. The trends are strongest for n = 3, m = 1 and gradually weaken as the size of the (mG/C)n block decreases (with a concomitant increase of (A/T)m). (A/T)2 nearest neighbor flank preferentially encloses the (G/C)n block (to produce (A/T)2 (G/C)n (A/T)m). The (A/T)2 flank trends are weaker than the (G/C)2 flank ones. The (A/T)2 flank trends also decrease in strength as the size of the (G/C)n block decreases. The statistical significance of these trends in eukaryotes is very high. A possible correlation with DNA structural parameters, in particular groove geometry, is discussed. PMID- 2268406 TI - Molecular structure of the complex formed between the anticancer drug cisplatin and d(pGpG): C222(1) crystal form. AB - The three dimensional molecular structure of the adduct formed between the anticancer drug cisplatin and a DNA dinucleotide d(pGpG) has been determined by x ray diffraction analysis at 1.37 A resolution and refined to a final R-factor of 0.11. This structure, solved by using data from a previously reported crystal form in the space group C222(1), resembles that found in the space group P2(1)2(1)2 (Sherman, et al., Science, 230, 412-417, 1985; ibid, J. Amer. Chem. Soc. 110, 7368-7381, 1988). In both structures, four crystallographically independent cis-[Pt(NH3)2(d(pGpG]] molecules aggregate into a tetrameric cluster that is stabilized by a large number of intermolecular hydrogen bonds and base base stacking interactions. In each molecule, the platinum atom is coordinated to the N7 atoms of two guanine bases arranged in a head-to-head orientation, resulting in a large dihedral angle between the guanines. Intermolecular guanine guanine base pairings between different intrastrand crosslinked molecules are used extensively in the crystal lattice. PMID- 2268408 TI - Modeling hydrogen bonds in three dimensions. AB - The effective potential between two hydrogen bonded atoms is calculated on the basis of the Lippencott-Schroeder bent bond model, taken to be a typical model interaction. We differ from other calculations in that the minimum energy configuration for the proton is treated adiabatically, its position being recomputed at each value of the larger atoms separation. We find the typical hard core to have been a consequence of an artificial restriction of the proton to a fixed angle with the larger atom axis, basically a one-dimensional assumption. Free to move in three dimensions, the proton is squeezed off the axis as the separation narrows, and the hard core feature is gone. Depending on the degree of bond bending, the anharmonicity of the bond may be diminished, eliminated, or even reversed. PMID- 2268409 TI - Irreversible changes occur in chromatin structure upon dissociation of histone H1. AB - The role of histone H1 in the actual interactions bringing about chromatin folding is investigated by studying the reversibility of its dissociation. H1 was dissociated by increase of the NaCl concentration and reassociated by dialysis, without removal from the dialysis bag. To scrutinize the fidelity of this stoichiometric form of chromatin reconstitution, we use circular dichroism, nuclease digestion, thermal denaturation and the sensitive electric birefringence method. No alteration of the repeat length and no nucleosomal sliding are observed upon the reassociation procedure. However, under all the different conditions investigated, the original value of the positive electric birefringence is never recovered, indicating an irreversible change of structure. CD and melting profiles confirm that DNA-protein interactions are modified, and orientational relaxation time measurements indicate that these structural perturbations affect the salt-induced transition of polynucleosomal fibers. The striking conclusion of these studies is that variations of ionic concentration are sufficient to induce irreversible structural alterations affecting the higher order folding of chromatin. It is of interest that the only sample which exhibits behavior upon reassociation comparable to that of native chromatin is the one which experienced the fastest salt transitions. We suggest that these conformational changes arise from the unbinding to DNA of certain basic tails of histone(s), and that a competition for DNA binding locations exists upon the reassociation. These results are then additional arguments (Mazen, A., Hacques, M.F. and Marion, C.,J. Mol. Biol. 194, 741-745 (1987)), to suggest that dissociation of H1 might modify a direct interaction between basic tails of core histones and H1. PMID- 2268410 TI - Boehringer Mannheim Award lecture. Phosphatidylcholine metabolism: masochistic enzymology, metabolic regulation, and lipoprotein assembly. AB - Phosphatidylcholine is apparently essential for mammalian life, since there are no known inherited diseases in the biosynthesis of this lipid. One of its critical roles appears to be in the structure of the eucaryotic membranes. Why phosphatidylcholine is required and why other phospholipids will not substitute are unknown. The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. Choline kinase, the initial enzyme in the sequence, has been purified to homogeneity from kidney and liver and also catalyzes the phosphorylation of ethanolamine. Most evidence suggests that the next enzyme in the pathway, CTP:phosphocholine cytidylyltransferase, catalyzes the rate-limiting and regulated step in phosphatidylcholine biosynthesis. This enzyme has also been completely purified from liver. Cytidylyltransferase appears to exist in the cytosol as an inactive reservoir of enzyme and as a membrane-bound form (largely associated with the endoplasmic reticulum), which is activated by the phospholipid environment. There is evidence that the activity of this enzyme and the rate of phosphatidylcholine biosynthesis are regulated by the reversible translocation of the cytidylyltransferase between membranes and cytosol. Three major mechanisms appear to govern the distribution and cellular activity of this enzyme. (i) The enzyme is phosphorylated by cAMP-dependent protein kinase, which results in release of the enzyme into the cytosol. Reactivation of cytidylyltransferase by binding to membranes can occur by the action of protein phosphatase 1 or 2A. (ii) Fatty acids added to cells in culture or in vitro causes the enzyme to bind to membranes, where it is activated. Removal of the fatty acids dissociates the enzyme from the membrane. (iii) Perhaps most importantly, the concentration of phosphatidylcholine in the endoplasmic reticulum feedback regulates the distribution of cytidylyltransferase. A decrease in the level of phosphatidylcholine causes the enzyme to be activated by binding to the membrane, whereas an increase in phosphatidylcholine mediates the release of enzyme into the cytosol. The third enzyme in the CDP-choline pathway, CDP choline:1,2-diacylglycerol choline-phosphotransferase, has been cloned from yeast but never purified from any source. In liver an alternative pathway for phosphatidylcholine biosynthesis is the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase. This enzyme is membrane bound and has been purified to homogeneity. It catalyzes all three methylation reactions involved in the conversion of phosphatidylethanolamine to phosphatidylcholine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2268412 TI - Isolation of a phospholipase-A2-like protein from human fetal intestine. Lysis of erythroid cells from bovine liver by this protein and porcine phospholipase A2. AB - Extracts of human fetal intestine contain factors that can stimulate or inhibit thymidine incorporation into fetal bovine erythroid cells. An inhibitory factor was purified to homogeneity by gel-permeation and reversed-phase high performance liquid chromatography. The inhibitory action was due to cell lysis. The first 25 amino acids of the N-terminal segment were identical to the human lung and pancreatic phospholipase A2. The isolated protein released arachidonic acid from 2-arachidonyl phosphatidylcholine. Porcine phospholipase A2 had the same effects as the intestinal protein, including its tissue-specific lysis of fetal bovine liver erythroid cells. No decrease of thymidine incorporation was seen in fetal bovine intestinal cells, 3T3 cells, or K562 cells incubated with the porcine enzyme. No release of hemoglobin or cell lysis was observed with human erythrocytes or fetal bovine erythrocytes. Porcine and bee phospholipases, which have low sequence homology, are nearly equipotent in inhibiting thymidine incorporation, whereas melittin and beta-bungarotoxin were less active than the pancreatic enzyme. These results support the tissue-specific effects observed with other phospholipases A2. The high sensitivity of liver erythroid cells towards some phospholipases A2 suggest that these enzymes may be involved in the elimination of hepatic erythroid cells at the end of gestation. PMID- 2268411 TI - Cellular functions of ascorbic acid. AB - It has long been suspected that ascorbic acid is involved in many cellular reactions. This is evident from the multitude of seemingly unrelated symptoms seen in scurvy. However, until recently, our understanding of its involvement was confined to its role in the synthesis of collagen. Studies in the past few years have unveiled mechanisms of its actions in collagen formation and many other enzymatic reactions. In addition, numerous physiological responses are reportedly affected by ascorbic acid. From the well-characterized enzymatic reactions involving ascorbic acid, it has become clear that in animal cells the ascorbate does not seem to be directly involved in catalytic cycles. Rather its major function seems to keep prosthetic metal ions in their reduced form. The role of ascorbate as a reductant in these enzymatic reactions complements its other antioxidant functions which have been recently appreciated, including that as a scavenger of free radicals. Therefore, it seems that the major function of ascorbate is to protect tissues from harmful oxidative products and to keep certain enzymes in their required reduced forms. However, it remains unclear how the deficiency of ascorbate leads to the pathological symptoms found in scurvy. PMID- 2268413 TI - Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents. AB - We had previously reported that 6-methylene progesterone, an inhibitor of 5 alpha reductase, the enzyme which converts testosterone to dihydrotestosterone, markedly inhibited growth of the androgen-dependent Dunning R3327-H rat prostatic tumors. We now find that the progesterone derivatives melengestrol acetate (MGA) and megestrol acetate (MA) inhibit both the androgen-dependent (Dunning R3327-H) and the androgen-independent (Dunning R3327-AT3) prostatic tumors. Growth of the AT3 tumors was suppressed by approximately 53% after 9 days of daily s.c. injections with MGA at 10 mg/kg body weight. MGA also caused a 54% weight reduction of the ventral prostate and a 53% reduction of the seminal vesicles. Adrenal weights were reduced by 42%. A 24-day oral treatment with MGA (at approximately 15-17 mg/(kg.day)) inhibited AT3 tumor growth by 59% and caused a weight reduction in the following tissues: prostate (46%), seminal vesicles (19%), testes (12%), and adrenals (52%). Under the same protocol, MA inhibited AT3 tumor growth by 32% and reduced the weight of the ventral prostate by 49% and the weight of the adrenals by 18%, but had no effect on the seminal vesicles and testes. The extent of the MGA-induced prostatic regression was accompanied by cytological changes similar to those effected by 6-methylene progesterone, i.e., shrinking of the acinar epithelium. The AT3 tumors in MGA-treated rats displayed a limited degree of apoptosis. Atrophy of the adrenal cortex and lowered plasma levels of corticosterone and dihydroepiandrosterone were also observed. A therapeutic role for MGA and MA against androgen-independent prostatic neoplasms in man is forecast by these observations. PMID- 2268414 TI - The cytoprotective effect of Trolox demonstrated with three types of human cells. AB - Trolox, a hydrophilic analogue of alpha-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocyte against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2'-azo-bis(2 amidinopropane) HCl). Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes. PMID- 2268415 TI - Traces of brain microtubule-associated proteins affect dynamic properties of microtubules. AB - A method is described for measuring the quantities of stable and dynamic microtubules in a population in vitro. The method exploits the tendency of dynamic microtubules to depolymerize rapidly after being sheared. Stable microtubules, such as those protected by microtubule-associated proteins (MAPs), are broken to a smaller size by shearing, but do not depolymerize into subunits. The usual difficulty with this procedure is that the tubulin released from the dynamic microtubules rapidly repolymerizes before the end point of depolymerization can be measured. This has been overcome by including a small quantity of tubulin-colchicine complex in the mixture to block the repolymerization. For a total of 24 microM tubulin in a polymerization mixture, 10 microM of the sample polymerized originally under the conditions used. When 1.05 microM tubulin-colchicine complex was added at the time of shearing, the dynamic microtubules depolymerized, but the tubulin was released was unable to repolymerize and a small fraction of stable microtubules that resisted shear induced depolymerization could then be detected. When traces of MAPs (0.23-2.8% by mass) were included in the tubulin mixture, the fraction of stable microtubules increased from 5% in the absence of added MAPs to 41% in the presence of 2.8% MAPs. All the MAPs in the mixture were found in the stable fraction and this stable fraction forms early during microtubule assembly. Calculations on the extent of enrichment of MAPs in the stable fraction indicated that as little as 4% MAPs in a microtubule protected it from shear-induced disassembly. The results suggest that low levels of MAPs may distribute nonrandomly in the microtubule population. PMID- 2268416 TI - Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver. AB - The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia. PMID- 2268417 TI - Comparison of D-beta-hydroxybutyrate dehydrogenase from rat liver and brain mitochondria. AB - The properties of D-beta-hydroxybutyrate dehydrogenase (BDH) from rat liver and brain mitochondria were compared to determine if isozymes of this enzyme exist in these tissues. The BDHs from these tissues behaved similarly during the purification process. The enzymes were indistinguishable by sodium dodecyl sulfate-polyacrylamide or acid-urea-polyacrylamide gel electrophoresis and they had identical isoelectric points. The BDHs from rat liver and brain were also quite similar in functional parameters determined by kinetic analysis and phospholipid activation of apo-BDH (i.e., the lipid-free enzyme). Antiserum against rat liver BDH inhibited both enzymes to an equivalent extent in a titration assay. The enzymes had similar patterns of peptide mapping by partial digestion with Staphylococcus aureus V8 protease, followed by immunoblotting using antiserum against the liver enzyme. These results suggest that the BDHs in rat liver and brain are very similar and possibly identical. PMID- 2268418 TI - Rapid isolation of substrate-quality plasmid DNA without CsCl-dye density gradients. AB - The isolation of plasmid DNA produced in transformed bacterial cells is essential for many molecular biology techniques. Two drawbacks to the widely used CsCl ethidium bromide method of preparation are the need for ultracentrifuge time and the generation of ethidium bromide waste. In this article we describe a method for the quick isolation of plasmid DNA without the use of an ultracentrifuge or ethidium bromide. PMID- 2268419 TI - Unexpected loss of genomic DNA from agarose gel plugs. AB - Intact chromosomal DNAs are routinely prepared by embedding cells in agarose plugs before lysis. The large sizes of the genomic DNAs cause their retention while other macromolecules diffuse into and out of the gel matrix during lysis, washing and restriction cleavage incubations. However, in an analysis of agarose embedded chromosomal DNAs cleaved with restriction enzymes, fragments larger than 30 kilobases were found to have eluted from the gel plugs. Since loss of fragments from gel plugs may affect qualitative and quantitative interpretations of electrophoretic patterns, an analysis of the diffusion of DNA segments from agarose plugs was performed. The two variables monitored were the time dependence and the DNA fragment size dependence of the diffusion process. The results indicate that small fragments (less than or equal to 2 kilobases) are quickly lost from 1% agarose gel plugs; moreover, significant amounts of large DNA segments (i.e., the 48.5-kilobase lambda phage chromosome) are also lost. In addition to urging caution in the analysis of restriction cleavage data, these observations suggest that intact small organelle genomes and extrachromosomal DNAs also may be lost from genomic DNAs prepared in agarose gel plugs. PMID- 2268420 TI - An improved method for oligonucleotide-mediated site-directed mutagenesis. PMID- 2268421 TI - A device to rapidly core out tissue culture plates for autoradiographic visualization of cells transfected with cDNA libraries. PMID- 2268422 TI - A simplified method of inserting radiolabeled nucleic acid probes into blotting bags. PMID- 2268423 TI - A simple and efficient method for recovery of DNA from gels. PMID- 2268424 TI - Optimization of routine transformation of Escherichia coli with plasmid DNA. AB - Methods to optimize resources and transformation efficiency of routine daily transformations of DH1 Escherichia coli prepared by three calcium chloride methods were investigated and compared with polyethylene glycol and Hanahan methods. The benefit of a heat-shock step, a preplating incubation step to allow expression of antibiotic resistance, use of log phase bacteria and prolonged storage of bacteria were investigated using pBR322 and pUC18 plasmid DNAs. Bacteria prepared by CaCl2 methods consistently gave efficiencies of 4 x 10(6) transformants/microgram of plasmid DNA or better and were overall the most labor- and resource-efficient methods. Use of log phase bacteria, a heat shock and an incubation step were found to be beneficial for freshly prepared bacteria for all methods. Prolonged storage of up to 30 days of bacteria prepared by the CaCl2 methods was beneficial, resulting in a sustained increase in transformation efficiency when selection was by ampicillin but not when by tetracycline resistance. Also found when using bacteria stored three days or longer was an increased transformation efficiency of stationary vs. log phase bacteria and an unchanged or even increased efficiency when the preplating incubation step was omitted. The Hanahan methods were the most labor and resource intensive and routinely gave efficiencies of 2 x 10(7). Higher efficiencies of 10(8) were obtained only with repeated trial and error and were not consistently reproducible. The polyethylene glycol method consistently gave efficiencies of 2 x 10(7), and bacteria could easily be prepared daily or frozen with a minimal decrease in efficiency. PMID- 2268425 TI - Chemical robot for enzymatic reactions and extraction processes of DNA in DNA sequence analysis. AB - A chemical robot capable of performing enzymatic reactions and extraction processes of DNA has been developed. The basic functions of this robot include handling of plastic tubes with caps, micropipetting, mixing, microcentrifuging and incubating. As a result, almost all of the pre-electrophoresis steps can be carried out. In addition, because these processes are automated, the working time of each process can be reduced. The reproducibility of the automated operation is equivalent to that of a skilled operator. PMID- 2268426 TI - Buffer solutes as stabilizers of 35S-amino acids: a study of volatility, radiochemical purity and biological activity. AB - It is well established that volatile radioactive compounds are associated with preparations of 35S-amino acids, but misconceptions still exist. The addition of stabilizers to these preparations has created a false sense of security regarding the evolution of these volatiles from cell culture medium. Experiments presented here show that the commercially used buffers L-lysine, tricine and 3,4-pyridine dicarboxylic acid all reduced, but did not eliminate, the evolution of 35S volatiles from tissue culture medium. In each case, the rate of release was approximately 12 nCi/mCi/day (or 0.001%), compared to approximately 44 nCi/mCi/day in the buffer's absence. None of six alternative buffers tested are more effective than the commercially used buffers. We found that the release of labeled volatiles is dependent on the nature of the culture medium, but is no greater from crude 35S-amino acid preparations than from purified 35S-methionine. These commercially used buffers are also effective in maintaining radiochemical purity and are compatible with biological activity; however, because these buffers do not entirely eliminate the release of radioactivity into the gas phase, routine safe-handling procedures should be practiced when working with these products. PMID- 2268427 TI - Sub-femtomole quantitation of proteins with Threshold, for the biopharmaceutical industry. AB - The Threshold system provides for rapid quantitation of a variety of analytes at sub-femtomole levels, which is fewer than 6 x 10(8) molecules. The operating principles of the measurement system will be described, including the means for chemical modulation of the signal and the subsequent signal detection utilizing a proprietary silicon sensor. The Immuno-Ligand Assay is a universal ligand-binding assay system which provides quantitative measurement of proteins (including antibodies) in a variety of biological media. Assay performance will be described, along with data demonstrating sensitivity, precision and accuracy, for a variety of analytes of interest to the biopharmaceutical industry. PMID- 2268428 TI - A simple assay for determining the capping efficiencies of RNA polymerases used for in vitro transcription. AB - We have developed an assay that uses phenyl boronate agarose column chromatography to measure the capping efficiencies of RNA polymerases used for in vitro transcription of cloned cDNAs. Capped 32P-labeled ovalbumin mRNAs were synthesized by in vitro run-off transcription with SP6 or T7 RNA polymerase in the presence of cap analogs and digested to completion with T1 and T2 RNase. The resulting 3'-nucleoside monophosphates (NMPs) and cap structures were separated by chromatography on phenyl boronate agarose, and the ratio of radioactivity between the two was used to estimate the extent of transcript capping. PMID- 2268429 TI - A rapid procedure for eliminating chromatofocusing buffer and concentrating minor active subforms of mitochondrial malate dehydrogenase. AB - Mitochondrial malate dehydrogenase from several sources contains different molecular forms whose origin is still under discussion. Separation of these subforms has been achieved by chromatofocusing. A simple and rapid method, based on 5' AMP Sepharose chromatography, has been developed to concentrate mitochondrial malate dehydrogenase subforms and simultaneously remove chromatofocusing buffer. PMID- 2268431 TI - Rapid and inexpensive desalting of chromatographic samples after HPLC. PMID- 2268430 TI - A protocol for the purification of bovine serum albumin free of deoxyribonuclease activity. AB - Bovine serum albumin, free of deoxyribonuclease activity, was obtained in our laboratory using ion-exchange chromatography followed by acetylation. Chromatography on four different resins (DEAE-52, P-11, hydroxylapatite and Q Sepharose fast-flow) was examined. Fractions from Q Sepharose chromatography, eluted with a linear gradient 0-1.0 M NaCl and subsequently acetylated, proved to be the most effective method for obtaining deoxyribonuclease-free bovine serum albumin. PMID- 2268432 TI - Simple, quick and efficient site-directed antibody immobilization in a cartridge. AB - A method is described for the simple, quick and efficient attachment of antibody within a cartridge for use as an immunoaffinity chromatography column. Antibodies are immobilized via their Fc regions through the use of periodate-oxidized carbohydrate functionalities of the immunoglobulin G. The method allows for the in situ coupling of the immunoglobulin G without prior removal of the oxidizing periodate solution. The entire procedure can be completed in 50 minutes. This method is especially useful for quick determinations of a particular monoclonal antibody's functionality or avidity towards a specific antigen. It may also be used in place of a conventional immunoaffinity column for the rapid isolation of small amounts of an antigen. This method will reduce the lengthy process of preparing an immunoaffinity column from several days to less than an hour. PMID- 2268433 TI - Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. AB - Rewarding properties of psychostimulants result from reduced uptake and/or increased release of dopamine at mesolimbic synapses. As exemplified by cocaine, many psychostimulants act by binding to the dopamine uptake transporter. However, this does not explain the action of other psychostimulants, including amphetamine. As most psychostimulants are weak bases and dopamine uptake into synaptic vesicles uses an interior-acidic pH gradient, we examined the possibility that psychostimulants might inhibit acidification. Pharmacologically relevant concentrations of amphetamine as well as cocaine and phencyclidine rapidly reduced pH gradients in cultured midbrain dopaminergic neurons. To examine direct effects on vesicles, we used chromaffin granules. The three psychostimulants, as well as fenfluramine, imipramine, and tyramine, reduced the pH gradient, resulting in reduced uptake and increased release of neurotransmitter. Inhibition of acidification by psychoactive amines contributes to their pharmacology and may provide a principal molecular mechanism of action of amphetamine. PMID- 2268434 TI - Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells. AB - The gene that is defective in Duchenne and Becker muscular dystrophies is expressed in the muscle and brain. However, the 5' ends of the 14 kb mRNA in these tissues are derived from two different exons, indicating the involvement of at least two promoters in the regulation of the cell-type and developmental specificities of expression of this gene. In the study presented here, we used the polymerase chain reaction and RNAase protection methods and various cell cultures to investigate the specificities of expression of these promoters. The results indicate a very stringent control of expression of the two promoters. In cloned rat myogenic cells, only the muscle-type dystrophin transcript was detected, and its presence was correlated with the formation of multinucleated fibers. In neuronal cell cultures, the brain-type transcript was detected. However, glial cell cultures expressed the muscle transcript only. Some cell lines derived from brain cells expressed both isoforms. PMID- 2268435 TI - Early and late survival of repaired type A aortic dissection. AB - From 1 January 1977 to 31 December 1988, 119 patients were operated upon for type A aortic dissection. The maximum follow-up was 11.7 years (median 5.6 years); follow-up was 100% complete. Actuarial survival was 47.3% +/- 5%. The death risk decreased rapidly to a constant rate of 0.0027 events/month after 3 months. There were 41 early deaths, mostly due to haemorrhage, brain damage and low output syndrome. A significantly higher probability of early death was observed in patients with preoperative myocardial ischaemia or infarction (P less than 0.0001) or preoperative cerebral symptoms (P = 0.0002). Extended dissection increased the risk proportionally to the length of the aorta involved (P = 0.0002). Typical dissection originating from an intimal tear in the ascending aorta had a significantly lower operative risk than atypical dissection with an intimal tear not localized in the aortic root (P = 0.0006). Of the 14 late deaths, 2 were unrelated to dissection, 2 were of unknown origin and 4 were sudden. Stroke was the cause of 2 and congestive heart failure the cause of 4 deaths. The probability of late death was higher in patients with perioperative brain damage (P = 0.003) and in patients with preoperative shock (P = 0.0025). It was significantly lower in patients with dissection of hypertensive aetiology (P = 0.002). There were 13 reoperations on 12 patients. Early reoperations were due to rupture of the distal aortic anastomosis. Late reoperations were mostly due to dehiscence of aortic valvular prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268436 TI - Pitfalls in intraoperative frozen section histology of mediastinal neoplasms. AB - We evaluated the reliability of intraoperative frozen section histology in 149 mediastinal tumours of which 106 lesions were localized in the anterior, 18 in the central and 25 in the posterior mediastinum. Gross non-resectability was ruled out by preoperative imaging. No preoperative cytological or histological diagnosis was obtained in any case. At thoracotomy, 3 biopsies from 3 different sites of the tumour were processed for frozen section as well as for paraffin histology and immunohistochemistry. In 67 of 73 benign lesions (91%), the intraoperative diagnosis was correct, 5 cases could not be classified by frozen section and 1 case had to be revised. Only 28 of 76 malignant lesions (36.8%) were diagnosed correctly by intraoperative frozen section. In 27 cases (35.5%), no intraoperative classification was possible and in 21 patients (27.6%), the diagnosis was wrong with the consequence of surgical overtreatment for lymphoma misinterpreted as thymic cancer in 3 cases. In patients in whom preoperative investigations suggest borderline resectability, a staged procedure to obtain histology prior to definitive surgery could prevent overtreatment. PMID- 2268437 TI - The effects of intraoperative hypothermia and cardiopulmonary bypass on trace metals and their protein binding ratios. AB - The ability of intraoperative hypothermia to modify the metabolic response to cardiopulmonary bypass (CPB) was assessed by serial alterations in iron, zinc and copper, and in their molar binding ratios to their respective transport proteins, in 20 male patients under-going elective coronary artery surgery and randomised to an operative blood temperature of 28 degrees C or 20 degrees C. Decreases in serum iron and zinc concentrations, typical of the acute phase response, were preceded by early rises. Significant alterations in the metal: protein molar binding ratios preceded significant changes in the serum concentrations of the metals and occurred earliest in the zinc: albumin binding ratio, which was apparent by the time of skin incision. An intraoperative temperature of 20 degrees C modified iron and zinc concentrations and their protein binding ratios during surgery but not in the post-operative period. These early changes in trace metals and their protein binding ratios are a simple and inexpensive method of quantitating the response to surgical injury and may be useful in assessing new interventions in cardiopulmonary bypass. An awareness of the trace element response to surgical injury is essential to avoid misdiagnoses of iron deficiency anaemia or zinc deficiency. PMID- 2268438 TI - Postoperative autologous transfusion in cardiac surgery. A prospective, randomised study. AB - To investigate the safety and efficacy of postoperative autologous blood transfusion (AT) using the Shiley hardshell venous reservoir, a prospective, randomised, controlled study was carried out in two matched groups of twenty patients undergoing elective coronary artery bypass surgery. The mean volume of shed mediastinal blood reinfused in the first 6 h postoperatively was 371.7 +/- 63.23 ml. Use of homologous blood was reduced from 760.5 +/- 108.37 ml in the control patients to 466.25 +/- 87.44 ml in the AT patients, a reduction of 38.7% (p less than 0.05). There was no statistically significant difference in the clinical outcome, overall blood loss, use of platelets, fresh frozen plasma and colloids, haematological indices, renal and hepatic functions, or clotting mechanism, although there was a reduction in the fibrinogen level in the patients who received AT (p less than 0.05). Mediastinal blood did not clot and was defibrinogenated. It contained significant levels of haemoglobin (8.175 +/- 0.506 g/dl), platelets (96.55 +/- 10.39 per mm3 10(3)), protein (42.5 +/- 1.13 g/l), calcium (2.385 +/- 0.054 mmol/l) and was well oxygenated (PO2 = 20.46 +/- 0.81 kPa). No patients developed bacteraemia or had any AT-related infections. We conclude that postoperative autologous transfusion using the Shiley hardshell venous reservoir is a safe and efficient method for reducing postoperative homologous blood requirement after coronary artery bypass surgery. PMID- 2268439 TI - Systemic atrioventricular conduit for extracardiac bypass of hypoplastic systemic atrioventricular valve. AB - The management of severe congenital mitral stenosis in infants and children is still controversial. We describe our experience with the use of a systemic atrioventricular (SAV) extracardiac conduit to bypass a hypoplastic systemic atrioventricular valve. An SAV extracardiac conduit has been used in six patients (left atrium--left ventricle in five, right atrium--right ventricle in one). One hospital death occurred due to mediastinitis and there were two late deaths, one due to progressive subaortic stenosis and one sudden, possibly due to arrhythmia. Postoperative cardiac catheterization performed in five patients showed reduction of the transmitral gradient from a mean of 16 mmHg to a mean of 5 mmHg. Calcification of the bioprosthetic valve occurred in two patients 3 1/2 years and 2 years respectively after the operation; one died from concomitant subaortic stenosis and one underwent conduit replacement. Although its long-term efficacy is limited, the SAV conduit seems the most reliable surgical option for infants and children with hypoplastic systemic atrioventricular valves unsuited to conventional surgery. PMID- 2268440 TI - Thromboembolic and bleeding complications after mitral valve replacement. AB - One thousand six hundred and sixty-eight consecutive patients who underwent isolated mitral valve replacement (MVR) from 1963 to 1984 were evaluated retrospectively. Thromboembolism occurred with a linearised rate of 2.5% +/- 0.2%/patient-year (PY) for Starr-Edwards disc prosthesis Model 6520, 2.4% +/- 0.3%/PY for Bjork-Shiley plane prosthesis, 3.0% +/- 0.8%/PY for Bjork-Shiley convexo-concave 60 degrees prosthesis, 3.0% +/- 0.8%/PY for St. Jude Medical prosthesis and 3.4% +/- 0.5%/PY for Carpentier-Edwards tissue valve without the differences reaching significance. In the SJM group, the incidence of thromboembolism was significantly higher (P less than 0.025) in smaller sizes (less than M29) probably due to a more turbulent flow. The linearised rate for major haemorrhage was 1.6% +/- 0.1%/PY. Twenty-three percent of the thromboembolic and 18% of the bleeding events were fatal. Sixty-eight percent of the emboli involved the central nervous system and bleeding apart from fatalities was predominantly non-cerebral (81%). Whereas thromboembolism was a time-related event with more than twice as high a risk in the first postoperative year (4.2% +/- 0.5% vs. 1.7% +/- 0.8%, P less than 0.01), bleeding occurred with a constant rate over time (0.9% +/- 0.4%). Adequacy of anticoagulation was an important risk factor for postoperative embolism with the prothrombin time (PT) exceeding the therapeutic range in 65% of all events. A preoperative history of embolism was the only additional patient-related risk factor for postoperative embolism (18.3% vs. 9.6%, P less than 0.001). In 30% of all haemorrhage, the PT was below 15%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268441 TI - Myocardial protection by simple systemic hypothermia without aortic occlusion. AB - Systemic hypothermia at 25 degrees-28 degrees C without chemical cardioplegia was used in 908 patients undergoing coronary artery bypass grafting. Local coronary artery flow was interrupted only during grafting of a distal anastomosis. Systemic perfusion pressure was maintained at 80-100 mmHg, hematocrit at 20%-25%, and pCO2 and pH were monitored during hypothermia according to the alpha-stat principle, while the left ventricle was vented routinely. Proximal anastomoses were performed just before extracorporeal circulation was started by only partially occluding the ascending aorta. Preoperatively 61.9% of the patients had had a myocardial infarction, and 44% had unstable angina. In 14% a severe lesion of the main stem of the left coronary artery was present. Left ventricular function was moderately depressed in 25% and severely depressed in 8% of the patients. Forty-eight patients (5.3%) were aged 70 years or older. The mean number of grafts placed per patient was 3.3. Perioperative myocardial infarction occurred in 3%. Death due to left ventricular failure occurred in 0.4%. No left ventricular assist devices were needed; an intra-aortic balloon pump was used in 1%; positive inotropic support was required in 3.8% of the patients. These results indicate that systemic hypothermia alone provides safe myocardial protection and in certain cases may be the method of choice, particularly if aortic cross clamping or administration of cardioplegic solution is contraindicated. In addition, this method provides rapid revascularization of a severely ischemic zone, as present after unsuccessful PTCA procedures. PMID- 2268442 TI - Uneven myocardial hypothermia among cardiac chambers during hypothermic myocardial preservation. AB - During the development of methods to protect the heart from ischaemic injury, attention has been focused on protection of the left ventricle. In an attempt to assess right heart preservation. 55 consecutive patients undergoing open heart surgery were studied. Mean aortic cross-clamp time was 59.3 +/- 29.4 min. Temperature probes were inserted into the right atrium (RA), right ventricle (RV), and left ventricle (LV). During cardioplegia, the mean myocardial temperatures of RA, RV and LV were 19.1 degrees +/- 4.1 degrees C, 12.7 degrees +/- 4.8 degrees C and 7.3 degrees +/- 3.4 degrees C, respectively. Of the LV temperature measurements, 67.2% were 10 degrees C or lower. By contrast, 94.1% of RA measurements and 58.5% of RV measurements were above 10 degrees C. The inhomogeneity of chamber temperatures was observed irrespective of the patient's disease or age and whether the atrium or right ventricle were open or not. Hearts with mitral regurgitation (MR), in contrast to mitral stenosis and stenoinsufficiency, had higher LV temperatures, similar to those in the RV. We conclude that there is uneven hypothermia among the three cardiac chambers during hypothermic cardioplegic arrest, regardless of disease states except MR and regardless of age and procedure performed. PMID- 2268443 TI - Tension hydropneumothorax as delayed presentation of traumatic rupture of the diaphragm. AB - Diaphragmatic rupture due to blunt trauma is well recognised though uncommon. Most cases are diagnosed at the time of injury, but a proportion remain undiagnosed, only to present some months or even years later. This "delayed" group can present in a number of ways, including chronic abdominal and chest problems or an acute crisis. Herniation of abdominal viscera is the most common sequel, with strangulation and gangrene as the most serious complication. This paper reports a case of delayed presentation of diaphragmatic rupture and herniation presenting as tension hydropneumothorax due to small bowel perforation. A short discussion addresses the problems in diagnosis of this condition. We believe this to be the first reported case of perforated small bowel leading to tension hydropneumothorax. PMID- 2268444 TI - Infected sternotomy wounds. PMID- 2268445 TI - [Study on the variable activity of nucleolar organizer regions in lymphocytes from patients with carcinoma]. AB - The activity of nucleolar organizer regions (NOR) in the peripheral lymphocytes from patients with lung, gastric, intestinal or breast carcinoma was studied with a combined method of Ag-staining and G-band. The frequencies of Ag-NOR were higher in chromosome 15 and sum total from patients with lung cancer, lower in chromosome 14 from patients with breast cancer, and lower in chromosome 14 but higher in chromosome 22 from patients with gastric cancer, as compared with those of controls. No significant variation of the frequencies of Ag-NOR was found in the patients with intestinal cancer. The results indicate that a dominant Ag stained NOR model is shown in the patients with different carcinoma, i.e., the active expression of rRNA genes may present a speciality concerning the location of carcinoma. PMID- 2268446 TI - [Spatial association of nucleotide substitutions during the evolution of DNA sequences]. AB - Evolutionary models for estimating the number of nucleotide substitutions between DNA sequences are evaluated with data from histone gene sequences of 7 remote species. It is found that the nucleotide compositions at the third codon position of H2A genes vary greatly among species and are highly correlated with the compositions at the first position of H2A genes, with those at the first and third position of H4 genes and with those in the up- and downstream sequences of H2A genes. This implies the existence of regional constraints over DNA sequences during the evolutionary process, which is different over species. Possible causes for the variations are increment of G + C content in higher eukarotypes, and chromosomal recombination, which brought the histone genes onto different isochores and thus under different selective or mutational pressures. Substitutions at different positions in a codon have been found not to be independent, probably due to multiple substitutions, i.e., single substitution events involving multiple sites. The implication of these results to phylogeny inferring is discussed. PMID- 2268447 TI - [Expression of constitutive heterochromatin by AluI restriction endonuclease treatment and CA3/DA/DAPI staining of domestic pig chromosome]. AB - The heterogeneity of constitutive heterochromatin in two domestic pigs has been studied by restriction endonuclease AluI banding, CA3/DA/DAPI banding and C banding techniques. The results show that the centromere constitutive heterochromatin can be subdivided into three types, which located in different chromosomes. It is found that there is correspondence between No. 13--18 chromosomes in pigs and No. 1, 9, 16, Y chromosome in human by comparing the banding patterns of AluI and CA3/DA/DAPI. Therefore, it is revealed that satellite DNAs in constitutive heterochromatin of chromosomes mentioned above are similar. PMID- 2268448 TI - [Effect of linkage disequilibrium on generation mean and variance and its detection in random mating population]. AB - Two varieties V2 and V12 and their descendents of Nicotiana rustica were used to create four artificial different cycles of random mating populations. The effect of linkage disequilibrium on generation mean and variance was explored theoretically and practically on the two of character flowering time (FT) and final height (FH). Results showed that evidence of linkage was found in mean and variance levels and the variance of both additive and dominance became smaller as the cycles of random mating increased. This is the evidence of coupling linkage. The effects of intensity of linkage and the degree of association of genes on generation mean and variance were also discussed in the paper. PMID- 2268449 TI - [Cloning and expression of E. coli glucose isomerase gene in Streptomyces lividans]. AB - E. coli glucose isomerase gene was cloned into Streptomyces lividans using shuttle plasmid vector pSE-3. First plasmid pXI203 was constructed in E. coli using plasmids pXI200 (containing 1.6 kb glucose isomerase gene) and pGEM-3 digested with EcoR1. Then, recombinant plasmid pSEX100 was also constructed in E. coli using plasmids pXI203 and pSE-3 digested with HindIII. When the pSEX100 was transformed into Streptomyces lividans protoplasts, recombinants were obtained on R5YE medium containing 50 micrograms/ml neomycin and 50 micrograms/ml thiostrepton. The results showed that the E. coli glucose isomerase gene cloned and expressed in Streptomyces lividans via the analysis of restriction enzyme digestion as well as the detection of the glucose isomerase activity. PMID- 2268450 TI - [Construction of Frankia genomic libraries and isolation of clones homologous to nodulation genes from Rhizobium leguminosarum]. AB - High molecular genomic DNAs were isolated by using the lysozyme plus achromopeptidase system from Frankia strains At4, Ccol and Hr16, the root nodule endophytes of Alnus, Casuarina and Hippophae respectively, and used to construct genomic libraries in pLAFR1, a broad host range cosmid vector within many gram negative hosts. The genomic libraries were screened by in situ colony hybridization to identify clones homologous to common nodulation genes of Rhizobium leguminosarum, based on the sequence homology of EcoRI-digested Frankia total DNA to nodABC from Rhizobium meliloti. Several clones showing relatively strong hybridization were found, the recombinant plasmid was isolated, and their homology with Rhizobium nodulation genes was confirmed by spot hybridization. Further work on these positive clones is now underway. PMID- 2268451 TI - Healthy people 2000. PMID- 2268452 TI - How can we help the remaining smokers to quit? PMID- 2268453 TI - The temporal pattern of reduction of mortality risk after smoking cessation. AB - We investigated the excess mortality risks of former smokers according to the number of years since they quit smoking in a cohort of 21,112 men and women evaluated with coronary angiography and included in the Coronary Artery Surgery Study registry. There is a prompt decline in mortality risk within the first year of quitting. Thereafter, former smokers have a sustained, modestly elevated mortality risk for at least 20 years compared with people who never smoked. The pattern is similar in men and women, in 35-54, 55-64, and greater than or equal to 65 age groups, and in subcohorts of those with coronary artery disease and those without coronary artery disease. PMID- 2268454 TI - Participation in a smoking cessation program: a population-based perspective. AB - We examined factors associated with participation in an HMO-based, self-help smoking cessation trial by comparing participants with nonparticipating smokers who responded to a prior health survey. Recruitment to the trial was accomplished through the HMO's monthly magazine sent to all enrollee households, and the health survey involved a random sample of the enrollee population. Participants were more likely to be female, older, better educated, and heavier smokers with more attempts to quit in the past. Participants consistently reported poorer levels of health status (self-perceived health and energy, life satisfaction, depression, and symptoms), less healthy lifestyles (exercise and dietary fat), and a greater conviction that smoking cessation would improve how they feel than nonparticipants. These findings confirm previous suggestions that formal cessation programs attract those with a more extensive history of addiction, prior failure, and pathophysiologic effects and may provide clues to increasing motivation among smokers with a greater likelihood of treatment success. PMID- 2268455 TI - The expected impact of a smoking cessation program for pregnant women on infant mortality among Native Americans. AB - To quantify the expected impact of a smoking cessation program for pregnant women on infant mortality among Native Americans, we estimated the proportional reduction (impact fraction) and the absolute reduction (impact risk) in neonatal and postneonatal mortality as a result of the intervention program. The estimated attributable fraction due to maternal smoking was 16.6% of infant deaths in the Aberdeen Indian Health Service (IHS) Area, 16.2% in the Alaska IHS Area, and 5.2% in the Navajo IHS Area. Under the assumptions that 14% of the smokers participating in a smoking cessation program would quit and that the intervention would have 60% relative efficacy in preventing infant deaths attributable to smoking, the impact fraction was estimated to be 0.9% of all infant deaths in the Aberdeen Area, 1.0% in the Alaska Area, and 0.3% in the Navajo Area. Under the "best" model assumptions (28% cessation rate and 90% relative efficacy), 2.6% of all infant deaths, 3.7% of postneonatal deaths, and 1.2% of neonatal deaths would be prevented by a smoking cessation program in the Aberdeen Area. When applied to 1984-1986 infant mortality data, the impact risk per 100,000 live births under the "best" model assumptions was 10 neonatal deaths and 41 postneonatal deaths in the Aberdeen Area, 10 neonatal and 34 postneonatal deaths in Alaska, and 2 neonatal and 8 postneonatal deaths in the Navajo Area. This report points to the need to develop effective smoking cessation programs for Native Americans, targeted in particular to women of reproductive age. PMID- 2268456 TI - Biochemical markers of compliance in the Physicians' Health Study. AB - The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study. PMID- 2268457 TI - Prevalence and correlates of depressive symptoms among older U.S. adults. AB - Using data from telephone interviews conducted during 1985, we investigated the prevalence and correlates of depressive symptoms in a national probability sample of 1,232 noninstitutionalized U.S. residents 65 years of age and older. The association between depressive symptoms and personal attributes, personal resources, illness behavior, life events, and self-reported health was examined through chi-square and logistic regression analyses. We measured depressive symptoms with the Center for Epidemiologic Studies--Depression (CES-D) scale using a score of 16 or greater as an indication of high depressive symptoms. Prevalence of high depressive symptoms was 9.9% in the total sample. For black males the prevalence of depressive symptoms was 7.4%, and for white males it was 6.8%. For black females the prevalence of depressive symptoms was 20.8%, while for white females it was 11.5%. In the regression analysis, female gender, single marital status, poor self-reported assessment of health, illness behavior, and a low number of club/organization memberships were significantly associated with high depressive symptoms. In comparison to respondents reporting good to excellent health, those reporting poor to fair health were almost four times more likely to report a high number of depressive symptoms (odds ratio = 3.97). PMID- 2268458 TI - [Internal ear dysfunction in systemic autoimmune diseases: study of sensorineural hearing loss probably originated by autoimmune disorders (preliminary study)]. AB - We analyse the inner ear disorders appearing in patients with autoimmune diseases. We have studied six patients with immunologic disorders and autoimmune sensorineural hearing loss, of a group of thirteen patients studied. The distribution was as follows: 1 systemic lupus erythematosus, 3 vasculitides (1 polyarteritis nodosa, 1 Churg-Strauss disease and 1 Behcet's syndrome), 1 relapsing polychondritis and 1 Vogt-Harada syndrome. The clinic aspects and immunological disorders are reviewed. PMID- 2268459 TI - [Presence and distribution of HLA-DR, HLA-DP and HLA-DQ transplant antigens in the human tympanum]. AB - The present morphological study was designed to investigate the expression of HLA class II subregion gene products on human tympanic membrane. Frozen sections from tympanic membrane of 10 cadavers were studied immunohistochemically using monoclonal antibodies. Positive reactions could be detected in the epidermal layer and the subepidermal connective tissue layer of the lamina propia. The implications of our findings on the clinical field of tympanic membrane allografting are discussed. PMID- 2268460 TI - [Infantile cholesteatoma]. AB - We present the results obtained in a group of 52 patients (55 ears), 15 years old or younger, diagnosed with middle ear cholesteatoma. After the evaluation of their clinical records, audiometry and X ray, surgery was performed by means of canal wall up procedures in 40 ears (72%) and canal wall down procedures in 15 (27%). The cholesteatoma was eradicated in 62% of the first group and in 86% of the second one. In 17 patients there was a recurrence. In those cases of canal wall up procedures they were transformed in canal wall down, or in the canal wall down the cavity was cleaned up. Only in 2 of these 17 recurrences, there was a second recurrence. In 7 cases a tympanoplasty was performed and the audiometric GAP was reduced in 57% and only in 19% when tympanoplasty wasn't performed. PMID- 2268461 TI - [Unusual forms of laryngeal carcinoma]. AB - From 1976 to 1983 we monitored 439 patients who were treated at the Radiotherapy Unit of University Clinic of Cadiz. Of all the patients who were examined we discovered only six cases of unusual histopathological forms of carcinoma of the larynx, representing 1.36%. The survival in the case of these patients was studied five years later. From the study we conclude that survival in the case of these patients is not affected by histopathological type of tumor, but, as in the case of epidermoid tumors, influencing factors are: anatomical situation, extension and type of treatment followed. The index of survival is similar to that observed in epidermoid neoplasm of the larynx. PMID- 2268462 TI - [Cancer of the mobile portion of the tongue: a review study]. AB - 32 cases of cancer of the mobile portion of the tongue are studied. Comments are made about its aetiology, diagnosis and results of different treatment techniques. PMID- 2268463 TI - [Cryosurgery for the treatment of vasomotor rhinitis]. AB - The authors expose usefulness of the cryosurgery for the management in vasomotor rhinitis. They report the technique and patient selection, the good results attained in a high percent of cases and the lacking of complications. PMID- 2268464 TI - [Parathyroid autotransplant in thyroid surgery]. AB - The postoperative hypoparathyroidism was studied in 176 patients that underwent a total o a wide subtotal thyroidectomy. The rate of this complication was compared between patients receiving a parathyroid autotransplantation (75 cases) and patients that did not. A 2.9% of non-transplanted patients developed a permanent hypoparathyroidism, that was observed in a 1.3% of non-transplanted patient. At variance, a transient hypoparathyroidism was twice more frequently observed in the transplanted group. PMID- 2268465 TI - [Nasal sarcoidosis. Report of the first case in Cuba]. AB - This paper describes the case of a 58-year-old woman suffering from nasal mucous membrane involvement from sarcoidosis, and stresses the importance of the otorhinolaryngological manifestations of this disease and the role of the ORL specialist in diagnosing it. We note that sarcoidosis may first appear in the form of this type of symptoms and that in cases of uncertain or unusual etiology, a histopathological study is essential in diagnosing this process. We then review the treatment used by different authors in the literature, which we also applied to our patient. PMID- 2268466 TI - [Carcinoma arising in thyroglossal duct cyst: presentation of a new case and review of the literature]. AB - Carcinoma arising in thyroglossal duct remnants is a rare even that appears in about 1% of all surgically treated cases. A survey of the literature reveals more than 100 reported cases. We present a new case of malignant transformation of thyroid remnants in thyroglossal duct cyst wall: a non invasive papillary carcinoma. Local resection by the Sistrunk method, without any other treatment, was considered curative. We also review the available literature regarding this entity. PMID- 2268467 TI - [Chondrosarcoma of the larynx and laryngectomy. Report of 2 cases]. AB - Two malignant tumors of cartilaginous origin are presented. Both demonstrated all histologic criteria of chondrosarcomas. Chondrosarcoma of the larynx seem to arise from hyaline cartilage, being the cricoid the mostly involved cartilage. The growth rate is very low, so that the first symptoms, as hoarseness or dyspnea, may be anodyne. The survival rates are directly related to histological grading. Chondrosarcoma are usually of low-grade malignancy. Local growth is predominant, metastarization has been described for high-grade types. Local recurrence may occur even after years. Surgery is the treatment of choice. PMID- 2268468 TI - [Irreversible bilateral amaurosis secondary to the course of ethmofrontal mucocele]. AB - We present a carrier of a mucocele ethmofrontal patient's case that relapsed after surgical treatments and that, subsequently, it caused an intense bilateral and amaurosis. This was attributed to the bilateral atrophy of the optician nerve secondary to the evolution of the own mucocele. It discussed the frequency of this kind of complications in the bibliographical revision made. PMID- 2268469 TI - [Pharyngeal keratosis]. AB - A case of keratosis pharyngis is presented. This disease is infrequent, benign and of etiology unknown. Clinically present horny outgrowths in the lymphatic tissue of the pharynx, but without symptoms. The horny projections sooner or later disappear spontaneously in months or years, however tonsillectomy seems to be indicated in all cases in which the symptoms are worrying the patient, who present an evident "cancerophobia" frequent symptom of this disease. PMID- 2268470 TI - [Giant calculus of the submaxillary gland]. AB - We report an unusual case of sialolithiasis submaxillary gland in a patient with chronic renal failure and secondary hyperparathyroidism. The salivary calculus had a size about 6 cm. of length and 1.5 cm. of diameter and came out near spontaneous passage. PMID- 2268471 TI - [Retropharyngeal hydatid cyst]. AB - We report the case of a 37 year old male from rural area who presented as an emergency with symptoms compatible with the existence of a retropharyngeal tumoration. By the clinic it suggested an abscess but the CT scan as compatible with a carcinoma. On complementary examinations it appeared in a chest X ray an image which strongly suggested the possibility of a hydatidic cyst of the lung. Specific serologic reactions supported this and post-surgical pathological study lately confirmed the diagnosis. We believe of interest reporting this case because of it's unusual localization and difficulty in diagnosis. PMID- 2268472 TI - Lectin cytochemistry on the stratum intermedium and the papillary layer in the rat incisor enamel organ. AB - Lectin cytochemistry was carried out to elucidate the role of stratum intermedium cells and papillary layer cells in amelogenesis, especially in the process of sugar incorporation and on membrane characteristics according to their cytodifferentiation. Regarding the lectin-reaction on the plasma membrane, little or at best a weak reaction of Con A, UEA-I, PNA, MPA and WGA was seen in stratum intermedium cells from the late differentiation stage to the early secretory stage of ameloblasts. Lectin-stainability in the stratum intermedium increased in accordance with the cytodifferentiation of ameloblasts. At the active secretory stage of ameloblasts, lectins intensely stained the plasma membranes of stratum intermedium cells. The plasma membranes of papillary layer cells at both stages of ruffle-ended and smooth-ended ameloblasts were stained by same lectins as well. The results therefore suggest that: 1) stratum intermedium cells bring about changes in the glycolipids and glycoproteins of their plasma membranes in accordance with the cytodifferentiation of ameloblasts; 2) they regulate the transport of mineral and/or organic materials between ameloblasts and extracellular fluid via highly charged plasma membranes generated by glycocalyx; 3) the cell-cell interaction of stratum intermedium cells with ameloblasts, in which carbohydrate-protein (endogenous lectin) interaction plays a significant role, is important for the cytodifferentiation of these cells. Regarding the papillary layer cells, the results suggest that they also regulate the transport of minerals by their charged plasma membranes and participate in the removal of the enamel matrix. PMID- 2268473 TI - A cytochemical study of glycocalyx and the membrane cholesterol of rat glomerular podocytes. AB - In order to elucidate the cytochemical properties of rat podocyte's membranes, the authors studied the constituents and distribution of glycocalyx and membrane cholesterol. Chromic-phosphotungstic acid (Cr-PTA) stain combined with enzyme digestive tests was used for the glycocalyx analysis. A digitonin fixation method was applied for the detection of membrane cholesterol. On the whole surface of podocytes, glycocalyx showed a strongly positive reaction to Cr-PTA. In normal rats, the reactivity on the urinary surface above the slit membrane of the podocyte foot processes was decreased after treatments with neuraminidase, hyaluronidase and heparitinase. The reactivity on the basal surface below the slit membrane disappeared only after treatment with chondroitinase ABC. In Puromycin Aminonucleoside nephrosis (PAN) rats, the foot processes were effaced extensively. Though a highly positive reactivity of Cr-PTA was observed on the urinary surface of the podocytes, the basal surface reacted weakly. The positive reaction of the urinary surface was not affected by the treatments with neuraminidase, hyaluronidase and heparitinase, but the weak reaction of the basal surface disappeared completely through chondroitinase ABC treatment. The distribution of membrane cholesterol was clearly revealed by the digitonin fixation method, showing digitonin cholesterol complexes of localized trilamellar structures. In normal rat podocytes the complexes were found on the urinary surface, with only a few on the basal surface. In PAN rats the complexes were seldom noticed either on the urinary or basal surfaces. The heterogeneous distribution of glycocalyx and membrane cholesterol seen in normal rat podocytes are changed remarkably under nephrotic condition. PMID- 2268474 TI - Histologic changes in the mouse testis after treatment with gossypol tetra-acetic acid. AB - The effect of oral administrations (20 or 40 mg/kg body weight/day, for 21 days) of gossypol tetraacetic acid on the testis of the Parkes strain mouse was investigated. Gossypol treatment did not affect the body weight or testicular weight, but caused a significant depression in the weight of the seminal vesicle. Histologically, the testes in mice treated with gossypol possessed regressed seminiferous tubules showing the exfoliation of germ cells, the occurrence of giant cells, a disorganization of the germinal epithelium, the degeneration of germinal elements, intraepithelial vacuolation and dislocation of the Sertoli cells into the luminal portion. However, the effect of gossypol was not uniform, and normal features were also observed in the majority of the tubules in the testes of the gossypol-treated mice. When quantitatively analysed, the frequency of regressed seminiferous tubules was significantly higher in the testes in the treated mice than the controls. The results suggest that the gossypol treatment induces non-uniform regressive changes in the seminiferous tubules in the mouse testis. PMID- 2268475 TI - Fine structural changes in the endolymphatic sac induced by calcium loading in the tree frog, Hyla arborea japonica. AB - The growth rate of calcium carbonate (CaCO3) crystals in the endolymphatic sac was modulated, and morphological changes in this organ were observed by light and electron microscopy. When calcium chloride (CaCl2) was given to the three frog for a short period (3 days to 2 weeks), CaCO3 crystal production was accelerated. Epithelial cells enlarged, their rough endoplasmic reticulum (rER) and Golgi apparatus developed, and dense material increased around CaCO3 crystals and/or in the endolymphatic lumen. In addition, multiluminal endolymphatic chambers appeared in some frogs. On the other hand, as the CaCl2 loading period lengthened and CaCO3 crystal formation decreased or stopped, the epithelial cells became flat and extended with scanty cytoplasm, and the rER and Golgi apparatus decreased in number and size. Furthermore, the amount of dense material around CaCO3 crystals and in the lumen decreased. These findings suggest that the rER, Golgi apparatus and dense material have key roles in the production of CaCO3 crystals. PMID- 2268476 TI - Immunohistochemical evidence of the extracellular localization of calcium activated neutral protease (CANP) in rabbit skeletal muscle, lung and aorta. AB - The subcellular localization of calcium-activated neutral protease requiring a millimolar calcium concentration (m-CANP) was examined by light and electron microscopy in various tissues of the rabbit, using an immunoperoxidase method with a monoclonal antibody (1C6D1). In skeletal muscles, specific staining for m CANP was recognized on collagen fibrils (ca 40 nm in diameter) with a periodic banding pattern. In the lung, dense reaction products were precipitated on elastic fibers under the bronchial epithelia. In the aorta, tunica intima and adventitia were intensely stained. Dense reaction products were observed on collagen fibrils and elastic fibers. Basal laminae, on the other hand, were not stained by anti m-CANP antibody in these tissues. These findings suggest that m CANP may be involved in the regulation of the structure and function of the extracellular matrix. PMID- 2268477 TI - Scanning electron microscopy of the auditory teeth along the mouse cochlear duct. AB - The auditory teeth in the spiral limbus of the cochlear duct are located under the limbal portion of the tectorial membrane and separated by furrows lodging the interdental cells. In this study, the shape, arrangement and distribution of the auditory teeth in the cochlear duct of adult mice were examined by scanning electron microscopy after removing the tectorial membrane and the interdental cells with chemical maceration methods. The auditory teeth appeared on the top face of the spiral limbus between the edge of the vestibular lip and the Reissner membrane. The teeth on the vestibular lip side possessed elongated upper plates and formed a continuous row resembling the keyboard of a piano; the teeth were separated by radially oriented parallel slits. The elongated teeth decreased in length from the base to the apex of the cochlear duct. The teeth on the Reissner membrane side showed star-shaped upper plates separated by slits and gaps. The population density of the star-shaped teeth decreased from the base to the apex, widening the gaps to hold the interdental cells. The upper plates of the teeth occupied about 75% of an extent of the tooth zone in the hook and first basal half turn, and about 55% in the apical turn. The regional differences of the auditory teeth are considered to be closely related to local functions of the tectorial membrane and the interdental cells. PMID- 2268478 TI - The action of capsaicin on primary afferent central terminals in the superficial dorsal horn of newborn mice. AB - Capsaicin was injected subcutaneously (50 mg/kg) into 10 mice on days 2 or 3 after birth, and 12 h, 3 and 5 days later the distribution and structure of degenerated primary afferent central axons or terminals (C-terminals) in the lumbar spinal dorsal horn were examined by electron microscopy. Degenerated terminal axons with dense or lamellar bodies or higher electron density were conspicuous 12 h after treatment with capsaicin. Severely degenerated unmyelinated axons, including dense or lamellar bodies engulfed by microglial cells, were numerous in the most superficial (marginal) layer, but rarely seen in the substantia gelatinosa. Two types of primary afferent central terminals in the substantia gelatinosa showed various extents of degeneration: small dark C terminals (CI-terminals) with densely packed agranular synaptic vesicles, and large light ones (CII-terminals) with less dense agranular synaptic vesicles and a few granular synaptic vesicles. Thus, many central axon terminals of dorsal root ganglion (DRG) neurons that are sensitive to capsaicin enter the marginal layer and substantia gelatinosa. Degenerated primary afferent central axons or terminals markedly decreased in the superficial dorsal horn 3 and 5 days after capsaicin treatment, still, there were many degenerating DRG neurons at this time as shown by our previous study. Previously we also reported that fewer slightly degenerating unmyelinated dorsal root axons and small DRG neurons appear at 12 h and larger DRG neurons degenerate later than smaller ones after treatment with capsaicin. As a result, the discovery of many severely degenerated terminal axons in the superficial dorsal horn soon after treatment supports the idea that capsaicin first acts on the central terminals and that this is followed by damage to larger DRG neurons. PMID- 2268479 TI - The quest for the permanent LVAD. We must continue, we must push forward. PMID- 2268480 TI - The need for intensive study of pericardial substitution after open heart surgery. PMID- 2268482 TI - Turning point in the management of pregnancies complicated by diabetes. Normoglycemia with self blood glucose monitoring of diet and insulin dosing. PMID- 2268481 TI - Clinical choices for circulatory assist devices. AB - Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure. In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart. Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas. Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices. Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems. Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patient's outcome when using these devices. Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection. Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications. PMID- 2268483 TI - Sensitivity of the artificial heart to changes in vascular resistance. AB - For conditions near those for normal operation, the cardiac output of the healthy natural heart is inherently sensitive to systemic venous resistance but is relatively insensitive to arterial resistance. A mathematical comparison was undertaken to discover the differences in the sensitivity of two configurations of artificial hearts to these resistances. It was found that one design incorporating independently pumping ventricles can be tailored to passively mimic the sensitivity of the natural heart. However, the other design with volumetrically coupled pumping is incapable of exhibiting similar sensitivity through passive means. PMID- 2268484 TI - Effective endothelialization of polyurethane surfaces. Response to shear stress and platelet adhesion. AB - Biomer and Mitrathane are thromboresistant polyurethane ureas that are suitable for coating artificial valves. Degeneration of the surface coatings, however, does occur over time, and in experimental animal studies adherent thrombi have been observed as a complication. In this study, morphometric techniques applied to scanning electron microscopy were used to assess whether vascular endothelial cells harvested from jugular veins of fetal lambs could be grown to confluence on these polyurethane surfaces, whether the monolayer would remain intact under conditions of shear stress (104 dynes/cm2), and whether this would result in decreased platelet adherence of sheep platelets relative to nonendothelialized surfaces. The results have shown that both Biomer and Mitrathane could be endothelialized: 88.8 +/- 5.1% of the Biomer surface consisted of intact confluent endothelial cells, as did 95.45 +/- 1.7% of the Mitrathane surface. After 6 hr of shear stress, a significant reduction in this feature was observed (p = 0.02), but both materials still maintained a high percentage of confluent endothelial cells (78.65% for Biomer and 85.58% for Mitrathane). After 48 hr of shear stress, however, the percent confluence was similar to control values, which suggested new cell growth. Endothelialized Biomer compared with Mitrathane had fewer adherent single platelets, or small or large aggregates (p = 0.001, p = 0.01, and p = 0.05, respectively); this feature was not affected by shear stress. Whereas endothelialization of the surface clearly decreased platelet adherence on Mitrathane (p = 0.01), only a trend was seen with Biomer. These studies therefore show that endothelialization of these polyurethane surfaces is feasible. PMID- 2268485 TI - Effect of extracorporeal membrane oxygenation on body water content and distribution in lambs. AB - Water content of the various body compartments were estimated immediately after beginning extracorporeal membrane oxygenation (ECMO), and daily thereafter for 3 days, in seven healthy 2-month-old lambs. Total body water, extracellular water, and plasma volume were estimated simultaneously by 18O, bromide, and T-1824 dilution, respectively. Volumes of intracellular water, interstitial water, blood, and red cells were calculated from the experimental estimates. No statistically significant changes occurred in the water content of the various body compartments in relation to duration of ECMO. The data suggest that water retention, clinically noted in human neonates treated with ECMO for persistent pulmonary hypertension, may be related to the primary disease process and/or its medical management, rather than to ECMO. PMID- 2268486 TI - The influence of dialysate sodium and variable ultrafiltration on fluid balance during hemodialysis. AB - An important factor in the development of hypotension during hemodialysis (HD) is a decrease in blood volume, due to ultrafiltration (UF) and an insufficient refill of the intravascular compartment. This insufficient refill might be caused by a transcellular fluid shift from the extracellular to the intracellular compartment. We studied the influence of dialysate sodium concentration and UF rate on the refill rate, blood volume, intracellular (ICV) and extracellular fluid volume (ECV). Three different HD strategies were studied in 15 patients: (A) conventional HD (dialysate sodium 140 mmol/L); (B) HD with a sodium profile (140-148 mmol/L); and (C) HD with a sodium profile and a variable UF rate (high low UF rate). ICV and ECV were measured by non-invasive conductivity measurements, blood volume was calculated from erythrocyte counts before and after treatment. Blood volume decrease was most pronounced during conventional HD, due to insufficient refilling without a detectable transcellular fluid shift. The sum of the decrease in ICV and EVC was less than during (B) and (C). The insufficient refill led to a higher prevalence of hypotension and cramps. The strategies (B) and (C) led to an significant and comparable transcellular fluid shift to the extracellular compartment. Thus, the use of a sodium profile led to a better intravascular refill and clinical tolerance of HD. Addition of a UF profile did not improve this any further. PMID- 2268488 TI - Evaluation of albumin loss during low-density lipoprotein apheresis. AB - Because the reduced plasma oncotic pressure from hypoproteinemia causes hyperlipidemia, serum albumin levels should be maintained during low-density lipoprotein (LDL) apheresis. The amount of albumin loss was evaluated in seven patients with familial hypercholesterolemia during LDL apheresis in which columns packed with dextran sulfate-cellulose beads were used as a selective adsorbent of LDL. Serum albumin level significantly decreased from 4.3 +/- 0.3 (mean +/- SD) g/dl to 3.6 +/- 0.2 g/dl. The albumin loss was assessed by two different methods: 1) radioimmunoassay of microalbumin content in the discarded fluid, and 2) measurement of changes in plasma albumin reserve. The albumin losses during one apheresis session were 3.7 +/- 2.9 g and 8.3 +/- 5.7 g, respectively, depending upon which of two different methods was used. There was a significant correlation between these two methods (r = 0.84, p less than 0.02). The amount of albumin loss during apheresis was estimated to be between 4.1% and 9.1% of total plasma albumin reserve, and more than half of the decreased serum albumin level appeared to be attributable to dilution due to the electrolyte solution used for priming of the extracorporeal circuit. PMID- 2268487 TI - Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals. AB - Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes. A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues. The skin button is designed to protect the tissues from damage and provide a secure material tissue interface. Prevention of superficial and invasive infection is the primary goal of the skin button. Eight calves were studied prospectively to identify gross or microscopic infection with the skin button. All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection. All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation. No animal died secondary to a skin button infection. Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects. PMID- 2268489 TI - Absorption of sulfamethoxazole and albumin from the peritoneal cavity. AB - The rates of disappearance of sulfamethoxazole and albumin from the peritoneal cavity were measured in humans. Albumin was added to the peritoneal cavity in concentrations commonly found during peritonitis (250-500 mg/100 ml) to ascertain if protein binding within the peritoneal cavity inhibited absorption from the peritoneal cavity. There were no statistical differences between the removal rates; 64-70% of the administered dose was absorbed after 180 min of intraperitoneal residence. The addition of albumin to the peritoneal cavity did not alter absorption of sulfamethoxazole. The total protein removed in dialysate effluent in the absence of albumin was 1,653 +/- 906 mg. The protein losses when albumin was added to dialysate [( albumin + control losses] - losses in dialysate drainage) were 1,037 +/- 2,305 mg and 1,364 +/- 1,653 mg for the 6 and 12 g studies. PMID- 2268490 TI - Conceptual basis for the organization and advancement of nursing knowledge: nursing diagnosis/taxonomy. AB - An analysis of the conceptualization embedded within the development of nursing diagnoses, including the historical perspective on this process, is presented. Although there are conceptual issues still to be resolved, nursing diagnosis can be considered as a conceptual approach to developing disciplinary knowledge. PMID- 2268491 TI - Implementing nursing diagnoses within the context of King's conceptual framework. AB - The use of nursing conceptual frameworks and nursing diagnoses is generally acknowledged to hold immense promise for the further development of nursing's scientific base. The nursing profession to date has failed to link the two, thus diminishing their impact. A large community hospital in Canada adopted King's Conceptual Framework for Nursing Practice and advocated the use of NANDA's nursing diagnostic statements as the manner by which patient needs or problems would be identified. Nurses, however, required assistance in identifying more clearly the connection between the theoretical base and nursing diagnoses. During stage one of this project a tool was designed that categorized NANDA's nursing diagnoses according to the concepts and systems of King's conceptual framework. The difficulties encountered in categorizing the nursing diagnoses are discussed and the categorization system is outlined. The utility of the tool was tested during stage two. A total of 25 nurses were asked to describe how they arrived at a particular nursing diagnosis before and after using the categorization tool. Criteria were used to indicate whether a connection had been made between the formulation of the nursing diagnosis and King's conceptual framework throughout the nurse's thought processes. The results indicated that nurses could make a connection between NANDA's nursing diagnoses and King's framework with the assistance of the categorization tool. PMID- 2268492 TI - Guidelines for submission of new diagnoses finalized. PMID- 2268493 TI - Differential diagnoses to altered parenting and ineffective breastfeeding. PMID- 2268494 TI - It pays to advertise. PMID- 2268495 TI - Effects of guided design and lecture teaching strategies on knowledge recall and on problem-solving performance of student nurses. AB - The purpose of this study was to compare the effect of guided design and lecture teaching strategies on the clinical problem-solving performance of first quarter student nurses. The guided design treatment (written simulations and small group interaction) was selected especially with a view of developing new approaches to teaching nursing diagnosis. A total of 50 students, enrolled in Fundamentals of Nursing, were randomly assigned to two treatment groups: guided design and lecture. Each group received 10 hours of instruction. Treatment groups remained intact for 6 weeks of clinical practice following instruction. Recall knowledge of the nursing process was measured by an objective examination, and performance in problem solving was measured through the use of a care plan evaluation tool. Data were analyzed using analysis of variance and t-tests. Students taught by guided design scored significantly higher than those taught by lecture in preparing a patient care plan for an actual patient and for a simulated patient. Knowledge of the nursing process as tested by an objective examination was not significantly different for the two treatment groups. PMID- 2268496 TI - Concept analysis of feeling: a human response pattern. AB - This article explores the concept of feeling, its historical foundations, and the use of this construct by other disciplines, e.g., philosophy and psychology. Feelings are well known and accepted as integral to human sensations and emotional experiences. One of the basic assumptions within nursing science is the notion that clients and nurses are emotional beings continually responding to the environment in a dynamic mind-body-spirit interaction. Phenomena classified within the taxonomic category of Feeling relate to a human response pattern involving the subjective awareness of information (NANDA, 1989). However, feeling as a human response has remained an underdeveloped and unrefined concept within nursing science. An operational definition is proposed in an effort to facilitate the classification of nursing diagnoses in regard to the holistic nature of persons. PMID- 2268497 TI - The control of proliferation and differentiation of early erythroid progenitors. PMID- 2268498 TI - Regulation of hematopoiesis by interleukin-1. PMID- 2268499 TI - Interleukin-3. AB - Interleukin-3 (IL-3) is a hemopoietic growth factor involved in the survival, proliferation and differentiation of multipotent hemopoietic cells. In five mammalian species, including man, the gene encoding IL-3 has been isolated and expressed to yield the mature recombinant proteins. The human IL-3 gene encodes a protein of 133 amino acids with two conserved cysteine residues and 2 potential N linked glycosylation sites; human native IL-3 has not been characterized. Comparison of the IL-3 genes revealed a more rapid evolutionary divergence than has been observed for other hemopoietic growth factors, and, hence, a more pronounced species specificity of the functional proteins was found. In agreement with its stimulatory action on immature multipotent cells, the in vivo actions of homologous recombinant IL-3 in nonhuman primates include a highly increased production of blood cells along the neutrophilic, eosinophilic and basophilic granulocyte as well as the monocyte, red cell and platelet lineages. PMID- 2268500 TI - IL4 and IL5: the role of two multifunctional cytokines and their place in the network of cytokine interactions. PMID- 2268502 TI - Humoral regulation of megakaryocytopoiesis. AB - If compared to erythroid and granulomacrophage lineages, the knowledge of the regulation of megakaryocytopoiesis has progressed slowly, and only the recent advent of specific clonogenic methods has permitted studies aimed at investigating this aspect of hematopoiesis. The analysis of Mk differentiation and platelet production is still difficult, because methods such as the 75SeM or 35S incorporation are time consuming and their sensitivity is relatively low. A number of laboratories have been able to purify, partially or to homogeneity, fractions stimulating the proliferation and differentiation of megakaryocytes. The biochemical identity between IL-3 and the active fractions found in the C.M. of some cell lines stands for a role of this hemopoietin in the regulation of megakaryocytopoiesis. However, the function of Epo and, above all, of GM-CSF cannot be ruled out, on the basis of experimental works, although only in some clinical trials GM-CSF seems to have been able to modify the platelet number. Hopefully, data on the therapeutic use of rhIL-3, and the sequentiation and identification of a molecule capable of action on the maturative compartment will shed new light on the regulation of megakaryocytopoiesis and the possibility to correct its disorders. PMID- 2268501 TI - Interleukin 6 (IL-6). PMID- 2268503 TI - The transforming growth factor-beta in the regulation of normal and leukemic myelopoiesis. PMID- 2268504 TI - Contractions to 5-hydroxytryptamine in human coronary artery and human saphenous vein. AB - Isometric contractions were obtained to 5-hydroxytryptamine receptor agonists in human saphenous vein and human coronary artery. Based on the interaction with the 5-HT2 receptor antagonist ketanserin, both 5-HT1 and 5-HT2 receptors are involved in contractions of human saphenous vein, but the predominant subtype involved in contractions of human coronary artery is the 5-HT1 receptor. PMID- 2268505 TI - T cell mediated induction of bronchial hyperreactivity. AB - Inadequate reactions of the immune system, i.e. allergic or hypersensitivity reactions, can lead to lung tissue injury. We investigated the relationship of type IV hypersensitivity, as an example of IgE independent hypersensitivity, with the induction of airway hyperreactivity. After antigen challenge (picrylsulphonic acid (PSA] in picrylchloride (PCl) sensitized mice, peribronchial and perivascular accumulation of mononuclear cells was found that was maximal 48 h after challenge. At several time points after challenge, changes in smooth muscle tone of mouse isolated tracheas were measured isometrically. In sensitized mice the response to carbachol was increased, reaching a maximum 48 h after challenge. This hyperreactivity was not found in athymic (nude) mice. We concluded from these data that airway hyperreactivity can be immunologically induced other than by IgE. PMID- 2268506 TI - Prostaglandin E2 inhibits and indomethacin enhances noradrenaline release in isolated kidneys of adult spontaneously hypertensive rats. AB - Renal neurotransmission and its modulation by prostaglandin (PG) E2 (0.06 microM) and indomethacin (10 microM) was investigated in isolated kidneys of adult spontaneously hypertensive (SHR) and normotensive control (WKY) rats. After preincubation with [3H]-noradrenaline the renal nerves were stimulated. The stimulation induced (S-I) outflow of radioactivity was taken as an index of noradrenaline release. The S-I outflow of radioactivity from SHR and WKY kidneys was similar but S-I pressor responses were enhanced in kidneys of SHR. PGE2 inhibited and indomethacin enhanced the S-I outflow of radioactivity in kidneys of WKY and SHR to a similar extent. This inhibitory effect of PGE2 is due to activation of inhibitory prejunctional PGE2 receptors. Neuronally released noradrenaline stimulates a local formation of PGE2 which then transjunctionally inhibits noradrenaline release. Renal noradrenaline release in the adult SHR and its modulation by PGs is not altered. An enhanced postjunctional responsiveness of the renal vasculature may contribute to the maintenance of hypertension in the adult SHR. PMID- 2268507 TI - Modulation of noradrenaline release from rat cortical kidney slices: effects of angiotensin I and II. AB - Rat kidney slices were incubated with [3H]-noradrenaline and placed into a superfusion chamber between two platinum electrodes. The kidney slices accumulated and stored radioactivity. In kidney slices taken from rats whose sympathetic nerve terminals were destroyed by pretreatment with 6-hydroxydopamine accumulation of radioactivity was abolished. The alpha 2-adrenoceptor antagonist idazoxan (0.1-1 microM) enhanced but tetrodotoxin (TTX, 1 microM) or omission of calcium from the superfusion solution abolished the stimulation induced (S-I) outflow of radioactivity. Angiotensin (A) I (3-300 nM) and AII (1-100 nM) enhanced S-I outflow of radioactivity. The effect of AI was markedly attenuated by the angiotensin converting enzyme inhibitor captopril (3 microM) and that of AII was blocked by the AII receptor antagonist saralasin (1 microM). These results suggest that the kidney slice preparation is a valid technique to study modulation of renal noradrenaline release. Endogenous noradrenaline released from sympathetic nerves in rat kidney slices activates prejunctional alpha 2 adrenoceptors to inhibit its own release. AII, which can also be formed locally from AI in these kidney slices, activates prejunctional AII receptors to facilitate renal noradrenaline release. PMID- 2268508 TI - Receptors, inositol polyphosphates and intracellular Ca2+. AB - 1. A large number of cell-surface receptors catalyse the activation of phospholipase C via a guanine nucleotide exchange protein and generate at least two important intracellular second messengers. One of these, inositol(1,4,5) trisphosphate, binds to specific intracellular receptors and releases Ca2+ from intracellular stores. 2. Subsequent metabolism of this messenger is complex, proceeding either by dephosphorylation or phosphorylation routes with the latter generating inositol(1,3,4,5) tetrakisphosphate which may have additional functional significance in Ca2+ homeostasis. 3. Calculations of the relative rates of metabolism through these routes as well as the development of new analogues of inositol polyphosphates have helped our understanding of these important cell signalling systems. PMID- 2268509 TI - The role of 5-hydroxytryptamine and 5-hydroxytryptaminergic mechanisms in hypertension. AB - 1. The possible role of 5-hydroxytryptamine (5-HT) and 5-HT-receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5-HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5-HT and its receptors in hypertension. 2. The following arguments would plead in favour of a certain role of 5-HT and 5-HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5 HT-induced constriction; the antihypertensive/vasodilator activity of the 5-HT2 receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5-HT. 3. However, at least as many arguments would deny a role of peripheral 5-HT in hypertension, like for instance: the fact that 5-HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the hyperresponsiveness of vessels from hypertensives is not specific for 5-HT; the elevated local concentration of 5-HT released by platelets is mainly limited to the microcirculation; the 5-HT2-receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5-HT2-receptor blockers like ritanserin and LY 53587 being inactive. 4. The various data and arguments available do not unequivocally support a relevant role of peripheral 5-HT and its receptors in hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268510 TI - Neuropeptides in hypertension: role of neuropeptide Y and calcitonin gene related peptide. AB - 1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfused mesenteric arterial bed, NPY and the structurally similar peptide intestinal polypeptide (PYY) decreased the periarterial nerve stimulation induced release of NA and potentiated the increase in perfusion pressure to nerve stimulation or exogenously applied agonists (e.g. angiotensin, vasopressin, phenylephrine). In contrast to NPY and PYY, C-terminal NPY fragments inhibited NA release and produced a parallel decrease in perfusion pressure thus supporting the concept of Y1 (post) and Y2 (pre) NPY receptors. 3. In the mesenteric artery of SHR the prejunctional inhibitory effect of NPY was attenuated while the postjunctional response was enhanced. 4. Following intrathecal (Int) injection of NPY, there was a decrease in blood pressure, total peripheral resistance (predominantly by a decrease in mesenteric vascular resistance) and renal nerve activity. The depressor effect of Int NPY was attenuated in the SHR. 5. Unilateral injections of NPY into the posterior hypothalamic nucleus increased blood pressure, hindquarter and renal vascular resistance and renal nerve activity. The pressor effect was enhanced in the SHR. 6. Periarterial nerve stimulation of the perfused mesenteric artery produced a frequency dependent vasodilation in beds pretreated with guanethidine and precontracted with methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268511 TI - Adenosine bronchoconstriction in asthma: investigations into its possible mechanism of action. AB - 1. Inhaled adenosine and its parent nucleotide, adenosine 5'-monophosphate (AMP) provoke bronchoconstriction in atopic and asthmatic individuals but not in normal subjects. 2. In clinical studies, histamine H1-receptor antagonists, cyclo oxygenase inhibitors and the mast cell 'stabilising' drugs, sodium cromoglycate and nedocromil, protect against the effects of adenosine bronchoprovocation suggesting the involvement of secondary mast cell mediator release. 3. Adenosine and its analogues potentiate histamine and leukotriene release from mast cells activated by other stimuli in vitro, and may also increase net mediator release from mast cells by counteracting the inhibitory effect of circulating adrenaline. 4. Although adenosine fulfils many of the criteria required for a mediator in asthma, its importance is not fully understood, and the mechanisms by which it provokes bronchoconstriction in asthmatic subjects is far from concluded. 5. Two possibilities are that either adenosine acts directly on luminal mast cells to upregulate histamine secretion, or it acts to initiate neuronal reflexes which stimulate histamine release indirectly and possibly activate peptidergic and/or cholinergic pathways. PMID- 2268513 TI - The aetiology and management of glossodynia. AB - In conclusion, glossodynia may present to a number of specialists. A wide variety of conditions may be responsible and the cause may be multifactorial. A systemic approach to assessment is essential and the opinion of other specialities, particularly dentistry, may be of help. Treatment is of the underlying cause but in many cases no specific aetiological factor is identified. The reassurance that there is no significant underlying pathology may in itself be sufficient to alleviate the symptom. PMID- 2268512 TI - The role of platelet activating factor in allergic respiratory disease. AB - 1. Platelet activating factor (PAF) is an ether-linked phospholipid capable of eliciting many of the factors of the allergic response including bronchoconstriction, mucosal oedema, eosinophil infiltration and bronchial hyperresponsiveness. 2. A wide range of selective PAF receptor antagonists have now been described which have been reported to reduce many aspects of allergen induced inflammatory responses in experimental animals. 3. Early clinical studies have indicated that some of these drugs are also effective PAF antagonists in man, but no controlled studies have been reported using these compounds in patients with allergic asthma. 4. The gingkolide mixture BN 52063 has recently been reported to inhibit allergen-induced cutaneous inflammation in man; a response which has certain pathological similarities to allergen-induced late onset airways obstruction in the lung. 5. Therefore, drugs antagonizing the actions of PAF may well lead to a better understanding of and may be a novel therapeutic approach for allergic respiratory disorders. PMID- 2268514 TI - Efficiency of treatment and monitoring of ablative radio iodine therapy for hyperthyroidism: a DGH centre study. AB - Sixty-three hyperthyroid patients received ablative dosages of radio iodine. The efficacy of this treatment and the follow-up were assessed one to two and a half years later from case records and general practitioners. Fifty-seven percent of patients were hypothyroid at six months and 65% at one year; 4.8% had failed to become euthyroid within one year; 68.2% of patients were on thyroxine at the time of survey. Two patients had not been seen by their doctor for follow-up and one patient stopped her thyroxine. Most general practitioners preferred patients to be returned to their care once thyroxine treatment was stabilised. Rapid responses and predictable outcome are important advantages of this form of therapy over established methods of management. Intentional ablation is particularly convenient in situations where clinical and biochemical follow-up may be difficult. Good communications and a computer-controlled recall system should ensure effective follow-up. PMID- 2268516 TI - Aspiration pneumonia as a cause of death. AB - This study of aspiration pneumonia is based on postmortem examinations carried out over a decade from 1979 to 1988 at York, on subjects of all ages and both sexes. The purpose of this study was not only to analyse the autopsy findings, but also to find out the real prevalence, the major causes leading to aspiration pneumonia, and its associated clinical features. PMID- 2268515 TI - An aid for the removal of compression hip screws. AB - The compression hip screw has a wide application in fracture management and elective orthopaedics. Due to the design of the sliding screw, bone ingrowth behind the threads can lead to difficulties in metalwork removal, especially in the younger patient. A simple technique is described using the plate to assist nail removal. PMID- 2268517 TI - Selenium status in disease: the role of selenium as a therapeutic agent. PMID- 2268518 TI - Comparison of oral erythromycin ethylsuccinate and ciprofloxacin in the treatment of acute respiratory tract infections. AB - A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single blind, multicentre study. The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents. Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group. In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms. This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections. PMID- 2268519 TI - Medical eponyms updated: 2. Graves' disease. PMID- 2268520 TI - False-positive diagnosis of adrenal phaeochromocytoma on metaiodobenzylguanidine (MIBG) [correction of MIGB] scan. PMID- 2268521 TI - Pericardial injury in a patient with pectus excavatum. PMID- 2268522 TI - Persistent granulomatous gastritis. PMID- 2268523 TI - Non-functioning or non-existent gall bladder? PMID- 2268524 TI - Spontaneous disappearance of multiple large calculi from the common bile duct. PMID- 2268525 TI - Halitosis and gastric outlet obstruction in infants. PMID- 2268526 TI - Childhood extradural haematomas, not always obvious. AB - Extradural haematomas in children are rare, but they may occur following a trivial head injury. We report a case where, following an unrecognised head injury to a three-year-old child, the insidious non-specific presentation of the extradural haematoma led to delay in the diagnosis and treatment. PMID- 2268527 TI - Near-fatal peptic ulceration and non-steroidal anti-inflammatory drugs (NSAIDs): two case reports. PMID- 2268528 TI - An unusual case of scleroderma associated with primary biliary cirrhosis. PMID- 2268529 TI - A case of Cri du chat syndrome. PMID- 2268530 TI - Neuroleptic malignant syndrome in a girl without psychosis. AB - We report a successfully managed case of neuroleptic malignant syndrome in which the diagnosis was delayed by one week because of the absence of an established psychiatric disease. A high degree of clinical suspicion must be maintained if the diagnosis of this rare, curable but often fatal, complication of neuroleptic therapy is not to be missed. PMID- 2268531 TI - Late recurrence of neuroblastoma: a report of five cases and review of the literature. AB - Late recurrence of neuroblastoma is uncommon. We report five patients who developed recurrent disease more than five years after diagnosis and review the literature on this subject. PMID- 2268532 TI - Infantile idiopathic thrombocytopenic purpura. AB - Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of the patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment. PMID- 2268533 TI - Influence of age, sex, and concurrent intrathecal methotrexate therapy on intellectual function after cranial irradiation during childhood: a report from the Children's Cancer Study Group. AB - Standard IQ tests were performed in 70 children and adolescents 3.5-10 years (median 5 yrs) after 24 Gy cranial irradiation, with or without concurrent intrathecal methotrexate, for central nervous system prophylaxis of acute lymphoblastic leukemia. Lower IQ scores correlated with younger age, female gender, and concomitant intrathecal methotrexate therapy. Multivariate analysis identified age as the most important determinant of the three factors. The lowest IQ scores were observed in girls who were less than 5 years old at the time of irradiation and who received concurrent intrathecal methotrexate. The observed adverse contribution of simultaneous intrathecal methotrexate therapy on IQ outcome may have significant implications for school performance, peer relationships, and occupational expectations. PMID- 2268534 TI - Educational achievements of survivors of childhood cancer. AB - The educational achievement of 37 long-term survivors of childhood cancer were matched with the sibling closest in age. Analysis of the sibling pairs revealed no significant difference in educational achievement between the study group and controls. A subset, who were treated with cranial prophylaxis, also showed no difference, but their numbers were small. PMID- 2268535 TI - Rescue after intermediate and high-dose methotrexate: background, rationale, and current practice. AB - Pharmacologic rescue methods used in combination with intermediate and high-dose methotrexate therapy are reviewed, with special emphasis on rescue with nucleosides and folinic acid. The mechanism of action, pharmacokinetics, and clinical applications of the rescue agents are described in detail in view of the literature and also of the own findings of the authors. In spite of the promising results of the in vitro studies and in vivo experiments in animal models, the clinical value of thymidine as a rescue agent remains to be determined. Currently, the only indication to use thymidine instead of folinic acid following high-dose methotrexate is to prevent toxicity related to extremely high methotrexate levels in patients with delayed elimination of methotrexate. In spite of the widespread application of folinic acid rescue, the exact mechanism of its action is not fully understood. The rescue dose and schedule in the majority of clinical protocols is empirical, and the start of the rescue administration is too early, allowing less than 36 to 42 hours of exposure to methotrexate. Clinical and laboratory findings indicate that while the early start of FA administration is unnecessary for protecting normal cells, it is potentially dangerous in terms of reduction of the antitumor effect of methotrexate. Our findings suggest that less than the most widely used 12-15 mg/m2 per dose rescue may be sufficient in preventing methotrexate related toxicity in patients with normal elimination of the drug. In addition, reducing the dose of the rescue may be beneficial to achieve better therapeutic results with high-dose methotrexate. Due to methodological problems, the pharmacokinetics of folinic acid rescue has not been excessively studied in humans. Recent data indicate that the pharmacokinetics of folinic acid in children is characterized by great intra- and interpatient variability. The effect of food on the bioavailability of folinic acid has not yet been studied, though it is most frequently administered orally. The introduction of the pure l-stereoisomer of the rescue agent in the clinical practice may eliminate potential interactions with the d-isomer, and may also simplify the introduction of therapeutic drug monitoring for folinic acid as well. This could lead to more rational clinical use of folinic acid as a rescue agent following intermediate and high-dose methotrexate therapy. PMID- 2268536 TI - Management of growth failure in the treatment of malignant disease. AB - Growth failure due to endocrine dysfunction as a result of treatment for malignant disease is becoming increasingly common. It may occur after cranial or craniospinal irradiation given in the treatment of acute lymphoblastic leukemia and brain tumors, and is often coupled with early or precocious puberty. It also occurs after neck and gonadal radiation and is particularly severe after total body irradiation where multiple endocrine deficiencies frequently occur. Failure to appreciate its occurrence or failure to institute therapy early enough may lead to short stature in adult life. Accurate and regular monitoring of standing and sitting height, bone age, and endocrine data should be undertaken by the oncologist in close collaboration with an endocrinologist, to ensure appropriate management of the patient. PMID- 2268537 TI - Familial essential thrombocythemia. AB - We report three siblings (2 F, 1 M) aged 9, 12, and 15 years with a thrombocytosis, above 650 X 10(9)/l for at least 18 months and a leukocyte alkaline phosphatase score below 37. The diagnosis of essential thrombocythemia was based upon the exclusion of a reactive thrombocytosis or another myeloproliferative disease. Cytogenetic examination of marrow cells was normal. PMID- 2268539 TI - Intussusception in acute childhood lymphoblastic leukemia: an unusual complication. PMID- 2268538 TI - Primary thyroid lymphoma in childhood: treatment with chemotherapy alone. AB - A 7-year-old boy developed primary non-Hodgkin's lymphoma (NHL) localized to the thyroid gland and was treated with combination chemotherapy alone. He has been continuously disease-free for 5 years since diagnosis, and is probably cured, without evidence of hypothyroidism or other unwanted late sequelae of external beam irradiation. Chemotherapy, alone, should be considered for the treatment of most, if not all, cases of localized NHL in childhood. PMID- 2268540 TI - Surface polarization in loach eggs and two-cell embryos: correlations between surface relief, endocytosis and cortex contractility. AB - The aim of this study was to examine the reorganization of the microfilamentous cortical layer (MC) accompanying ooplasmic segregation in loach eggs. Using scanning (SEM) and transmission electron microscopy (TEM), we found that the MC is thicker in folded areas. Prior to fertilization, surface microvilli are distributed more or less uniformly throughout the egg. A similar, more or less uniform, distribution of endocytotic events was observed in the eggs 5-15 min after insemination using fluorescence microscopy of Lucifer yellow CH uptake. During ooplasmic segregation, the surface is progressively polarized so that before the first cleavage onset (50-60 min after insemination) only the blastodisc surface is folded and undergoes endocytosis, whereas the vegetal surface is smooth and does not show internalization. In two-cell embryos, the blastomeric surface is also regionalized according to its relief and endocytosis. When surface tension was lowered by sucking most yolk granules out of the egg, we observed contractile responses only in the animal folded surface. These data suggest that a polar distribution of contractile structures is established in the loach egg undergoing ooplasmic segregation. PMID- 2268541 TI - Astroglial differentiation from neuroepithelial precursor cells of amphibian embryos: an in vivo and in vitro analysis. AB - Initial development of astroglial phenotype has been studied in vitro in an amphibian embryo (Pleurodeles waltI), to document the differentiation potentialities acquired by neural precursor cells isolated at the early neurula stage. In particular, we sought to determine whether interactions between neuroepithelial cells and the inducing tissue, the chordamesoderm, are required beyond this stage to specify precursor cells along glial lineages. Glial cell differentiation was documented by examining the appearance of glial fibrillary acidic protein (GFAp), a specific marker of astroglial lineages. Cells expressing GFAp-immunoreactivity differentiated rapidly, after 48 hours of culture, from cultivated neural plate cells, irrespective of the presence or absence of the inducing tissue. The widespread expression of Pleurodeles GFAp protein in neural plate cultures, in which CNS precursor cells develop alone in a simple saline medium, showed that prolonged contact with chordamesodermal cells was not necessary for the emergence of the astroglial phenotype. In addition, the initial development of astroglial phenotype has been defined in vivo. The first detectable GFAp-immunoreactivity was visualized in the neural tube of stage-24 embryos, a stage corresponding to 2-3 days in culture, defining radial glial cell end-feet. Thus, dissociation and culture of neural precursor cells did not appear to modify the onset of astroglial differentiation. At stage 32, GFAp immunoreactivity was observed over the entire length of radial glial fibers and was also evidenced in mitotic cells located in the ventricular zone, suggesting that radial glial cells were not all post-mitotic. PMID- 2268542 TI - Differential germ cell proliferation in the salamander pleurodeles waltl: controls by sexual genotype and by thermal epigenetic factor before differentiation of sexual phenotype of gonads. AB - In the acceptance that, during early gonadogenesis, variations of germ cell (GC) proliferation express interactions between germ and somatic cells, early events occurring before histological differentiation of gonadal sex has been detected and timed through GC counts on larvae of Pleurodeles waltl (urodele amphibia) issued from male ZZ or female ZW monosexual offspring. Gonads differentiate in accordance with sexual genotype in ZZ and ZW larvae at room temperature and in ZZ larvae at 32 degrees C whereas they are sex-reversed at 32 degrees C in ZW larvae, becoming phenotypic neomales. At both the rearing temperatures, in genital ridges, GCs do not proliferate during a period called P0 period ending earlier in ZZ than in ZW larvae. The time when proliferation starts depends on sexual genotypes and determines a ZZP0 period shorter than ZWP0 period. After P0 period, at room temperature, a moderate increase in GC number determining a P1 period is observed in both ZZ and ZW larvae, whereas a strong proliferation, determining a P2 period, occurs on a differential pattern in ZZ and ZW larvae; thus, before sexual differentiation of gonads, ZW females have more GCs than ZZ males. At 32 degrees C, GC proliferation is moderate during P1 period and does not accelerate during P2 period in ZW larvae differentiating neotestes; they have a lower GC number than ZZ larvae reared at 32 degrees C. Thus, during P2 period, at both room temperature and at 32 degrees C, GC number correlates with future phenotype of gonads. Results suggest that differential molecular events arise during early gonadogenesis and that testes may differentiate in different ways according to whether phenotype conforms to genotype or sex reversion occurs. PMID- 2268543 TI - Pattern formation in the epithelium of the oviduct of Japanese quail. AB - Cellular patterns of the oviduct epithelium from the Japanese quail were examined during maturation. The epithelium of a juvenile bird showed a jigsaw puzzle pattern consisting of a single, undifferentiated cell type. At the start of maturation, cells were rearranged into a pattern in which the length of boundaries between goblet type gland (G-) cells and ciliated (C-) cells (G-C boundaries) were maximized. At this stage, the surface area of G-cells was much smaller, but G-cells are more than 2 times more numerous than C-cells. Cells than gradually rearranged themselves into the checkerboard pattern through an increase in the proportion of C-cells and enlargement of the G-cells. At all times of maturation, the length of G-C boundaries was maximized. These observations strongly support the theory that the cellular pattern of the quail oviduct epithelium is spontaneously constructed by maximizing the length of boundaries between two different types of cells owing to the fact that theirs is the greatest adhesion capacity (Yamanaka and Honda, 1990). PMID- 2268544 TI - [The clinical and epidemiological aspects of a focus of epidemic keratoconjunctivitis]. AB - An outbreak of epidemic keratoconjunctivitis was followed from October 5 to November 14, 1987, in a Transylvania city, from clinical, epidemiological and virological points of view. Fixation of complement and seroneutralization was used in view of identification of the virus strains isolated from the outbreak. PMID- 2268545 TI - Measles antibodies in HIV-1 infected children. PMID- 2268546 TI - Some reasons of insufficient efficiency of anti-influenza vaccination. PMID- 2268547 TI - Demonstration of "all or none" rule in the antiviral activity of complement. PMID- 2268548 TI - [An immunofluorescence study of the viral and inframicrobial flora of the pharynx in 0- to 5-year-old children with acute respiratory diseases]. AB - The pharynx viral and inframicrobial flora of 52 0-5-year-old children with acute respiratory diseases was investigated through the immunofluorescence techniques. Results showed a high positivity rate (91% to 95%), the simultaneous presence in most of the patients of two to five antigens and the dominance of parainfluenza type 3 virus. The significance of the pharyngeal flora is discussed from an immunologic point of view. PMID- 2268549 TI - Sex steroids and osteoporosis: effects of deficiencies and substitutive treatments. AB - Adult mammalian bone is continuously renewed by the process of remodelling. In young healthy adults the amount of bone that is resorbed by osteoclasts is replaced by osteoblasts so that no net loss of bone occurs. In a situation of reduced sex hormone levels, such as in females after menopause or ovariectomy, in males after orchidectomy, or in patients of either sex with gonadal dysfunction, there is an imbalance between bone resorption and bone formation resulting in bone loss. The various hypotheses to explain the aetiology of this imbalance are reviewed. Substitution therapy of females with oestrogen results in the prevention of oestrogen deficiency-induced bone loss. It is generally agreed that the effect is due to inhibition of bone resorption. Recent in vitro data, however, indicate that oestrogens also have the capacity to stimulate the proliferation and functioning of bone-forming cells. Prevention of oestrogen deficiency-induced bone loss can also be achieved by treatment with high doses of progestagens. Available data suggest that this too is caused by resorption inhibition. The aim of treatment of females, who have lost so much bone that there is an increased risk of fractures after minimal trauma, is to increase bone mass rather than to prevent further bone loss. This can be accomplished by treatment with anabolic steroids. Both biochemical and histological data indicate that anabolics stimulate the activity of functioning osteoblasts. The increase in bone mass during continuous treatment is temporary because anabolics most probably also inhibit bone resorption. Substitution therapy with anabolics or androgens in males is equally effective and increases trabecular bone mass in the spine. PMID- 2268550 TI - Influence of culture conditions on the estrogenic cell growth stimulation of human breast cancer cells. AB - 17 beta-Estradiol is a potent mitogen for hormone-dependent cell lines (MCF-7, T47D and ZR 75.1). However, the degree of hormone sensitivity is very much influenced by culture conditions. In order to understand which factors modulate estrogenic effects on cell growth, four different culture conditions were used: (a) medium with dextran-coated charcoal-treated fetal calf serum (DCC-FCS); (b) medium with dextran-coated charcoal-treated growth factor-inactivated serum (DCC FCSd); (c) serum-free medium, after a 24-h incubation with serum to allow cell attachment; and (d) serum-free medium on collagen IV-treated plates. In all cell lines the highest cell growth stimulation was achieved when estradiol was added in the presence of 5% DCC-FCS, whereas reducing or removing serum from the culture medium resulted in a decrease in cell proliferation stimulation. We postulate that serum contains some still unknown components able to modulate the degree of estrogenic action in endocrine-dependent breast cancer cell lines. PMID- 2268551 TI - Structural requirements for the binding of dexamethasone to nuclear envelopes and plasma membranes. AB - The specificity of dexamethasone binding sites on nuclear envelopes (NE) and plasma membranes (PM) was determined in competition studies with natural and synthetic steroids. The binding affinities for nuclear envelopes and plasma membranes were then correlated with the three-dimensional structures of the ligands. Three major factors are implicated in the ability of the steroid to bind to the membrane sites: (1) the separation between the terminal oxygen atoms substituted at atoms C3 and C17, or attached to the substituent at C17, is found to be longer than 10 A for the medium and high affinity steroids; (2) the beta orientation of the oxygen atom in the C17-substituent to the D-ring is favored over alpha-orientation; and (3) bulky substituents and nontypical configurations are not accepted by the binding sites. A nearly linear correlation between the O3...O (substituted at C17) distance and the binding affinity of the tested steroids is observed; explanations for the lack of linear correlation of some steroids are given. A preliminary model for the interaction of steroids with these membrane sites is proposed which requires two hydrogen bonding regions that interact with the 2 oxygen atoms and some steric restriction sites that prevent the binding of steroids with large substituents. The hydrophobicities of the steroids do not correlate with binding affinities to the dexamethasone binding sites; hydrophobicity seems to play a minor role in these steroid-membrane interactions. Comparisons of the specificity of the dexamethasone binding sites on membranes to the specificity of various steroid receptors are also presented. PMID- 2268552 TI - Purification of the NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase from female rat pituitary cytosol. AB - The NADPH:5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) [EC 1.1.1.50] which catalyzes the reversible conversion of 5 alpha pregnane-3,20-dione (5 alpha-dihydroprogesterone; 5 alpha-DHP) to 3 alpha-hydroxy 5 alpha-pregnan- 20-one (3 alpha-,5 alpha-tetrahydroprogesterone; 3 alpha,5 alpha THP) was purified to apparent homogeneity from female rat anterior pituitary cytosol by a three step micro-purification procedure. Specific activity of purified 3 alpha-HSOR was enriched 438-fold from that in pituitary cytosol using successive ion exchange, chromatofocusing and affinity column chromatography purification steps. 3 alpha-HSOR appears to be a monomer with an approximate molecular weight of 36 kDa and an isoelectric point of about 5.75. The purified enzyme appears as a single protein staining band (36 kDa) when examined by polyacrylamide gel electrophoresis and with both silver or Coomassie blue staining. Under non-dissociating electrophoretic conditions, all of the 3 alpha HSOR activity co-migrated with the 36 kDa protein staining band. The purified enzyme in the presence of the preferred cofactor, NADPH, has an apparent Km for 5 alpha-DHP of 82 nM and a Vmax of 1.2 mumol of 3 alpha,5 alpha-THP formed per mg protein/30 min. The Km for NADPH was 0.71 microM. In the oxidative direction, the enzyme in the presence of NADP+ has a Km for 3 alpha,5 alpha-THP of 1.4 microM and a Vmax of 9.7 mumol of 5 alpha-DHP formed per mg protein/30 min. The Km for NADP+ was 1.6 microM. PMID- 2268553 TI - Glucocorticoid effects and receptors in two rat colon carcinoma cell lines differing by their tumorigenicity. AB - Steroid hormones, regulators of cell differentiation and proliferation, are believed to play a role in carcinogenesis. Glucocorticoid hormones in particular modulate the expression of a number of proteins implicated in this process. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon hormonal treatment, glucocorticoid hormones induced fibronectin secretion by the two clones, whereas PROb cells were found to secrete an additional Mr approximately 43,000 protein. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The progressive cells (PROb) contained more specific glucocorticoid binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody was found to be more degraded in the progressive cell line. PMID- 2268554 TI - Inhibitory effect of synthetic progestins, 4-MA and cyanoketone on human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase activity. AB - Human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene isomerase (3 beta HSD) purified from human placenta transforms C-21 (pregnenolone and 17 alpha hydroxy pregnenolone) as well as C-19 (dehydroepiandrosterone and androst-5-ene-3 beta, 17 beta-diol) steroids into the corresponding 3-keto-4-ene-steroids and is thus involved in the biosynthesis of all classes of hormonal steroids. Trilostane, epostane and cyanoketone are potent inhibitors of 3 beta-HSD with Ki values of approximately 50 nM. 4-MA, a well known 5 alpha-reductase inhibitor, is also a potent inhibitor of 3 beta-HSD with a Ki value of 56 nM. Synthetic progestin compounds such as promegestone and RU2323 show relatively strong inhibitory effects with Ki values of 110 and 190 nM, respectively. Cyproterone acetate, a progestin used in the treatment of hirsutism, acne and prostate cancer as well as norgestrel and norethindrone that are widely used as oral contraceptives also inhibit 3 beta-HSD activity at Ki values of 1.5, 1.7 and 2.5 microM, respectively. PMID- 2268556 TI - Rates of dissociation of sex steroid hormones from human sex hormone-binding globulin: a reassessment. AB - A rapid filtration assay employing dextran-coated charcoal as acceptor particles for free hormone was used to measure the rates of dissociation of dihydrotestosterone (DHT), testosterone (T), and estradiol (E2) from their binding proteins in human serum at 37 degrees C. Because measurements were begun after each hormone had fully (greater than 99%) dissociated from albumin, the observed rates of dissociation correspond to the rates of dissociation of the sex hormone-binding globulin (SHBG)-hormone complexes. The dissociation rate constants of the hormone-SHBG complexes were determined to be 0.016 +/- 0.001, 0.056 +/- 0.002, and 0.083 +/- 0.003 s-1 for DHT, T, and E2, respectively, corresponding to half-times of dissociation (t1/2) of 43, 12 and 8.4 s, respectively. The physiological significance of these findings can best be appreciated by comparing these t1/2 s with the capillary and sinusoidal transit times of various tissues (less than 1 s to approximately 10 s). PMID- 2268555 TI - Rates of dissociation of steroid and thyroid hormones from human serum albumin. AB - A rapid filtration assay employing dextran-coated charcoal as acceptor particles for free hormone was used to measure rates of dissociation of steroid and thyroid hormones from human serum albumin. Modification of a previously described assay allowed measurements at 1-s intervals. Nevertheless, this still permitted only minimum estimates of the dissociation rate constants. The hormones studied were thyroxine, 3,5,3'-triiodothyronine, cortisol, corticosterone, testosterone, dihydrotestosterone, estradiol, progesterone, and aldosterone. The apparent dissociation rate constant of the thyroxine-albumin complex at 37 degrees C was 1.3 +/- 0.2 s-1 (t 1/2, 0.5 s). The apparent dissociation rate constants of the other hormone-albumin complexes at 37 degrees C generally exceeded 2 s-1 (t 1/2 less than 0.35 s). Apparent dissociation rate constants at 4 degrees C were only slightly lower. These findings indicate that steroid and thyroid hormones dissociate from albumin rapidly compared with the 1-s capillary transit times that characterize many tissues. PMID- 2268557 TI - Aromatase inhibition by flavonoids. AB - Several synthetic flavones were found to inhibit the aromatization of androstenedione to estrone catalyzed by human placental microsomes. Twenty-one compounds were tested and the IC50 of the most active were: flavone, 10 microM; 7 hydroxyflavone, 0.5 microM; 7,4'-dihydroxyflavone, 2.0 microM; flavanone, 8.0 microM; and 4'-hydroxyflavanone, 10 microM. Most of the others had IC50 values ranging from 80 to greater than 200 microM. These findings show that 4' hydroxylation results in either no change or very little change in IC50 for flavanone, isoflavone and isoflavanone as well as other ring A hydroxylated flavones. Derivatives of flavone with a hydroxyl substituent at position 5, 6 and 7 were also screened. 7-Hydroxyflavone (11) was the most effective competitive inhibitor (IC50 = 0.5 microM) with an apparent Ki value of 0.25 microM. Compound 11 also induced a change in the absorption spectrum of the aromatase cytochrome P 450 which is indicative of substrate displacement. The relative binding affinities of the flavonoid analogs were determined and only ring A adn ring B dihydroxylated analogs were found to bind to the estrogen receptor. PMID- 2268558 TI - Synthesis of 4,19-disubstituted derivatives of DOC. Radioreceptor assay of some corticosteroid derivatives in human mononuclear leukocytes. AB - Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to type 1 receptors in human mononuclear leukocytes. 11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione (2) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5, accompanied by 4,21 diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one (6) and 21-acetoxy-11 beta,19 epoxy-4-hydroxypregnane-3,20-dione (7). With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione (8) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20 dione (10) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione (11) and the 9,11-dihydro derivative of the latter. Treatment of 10 with warm HCl furnished 19 chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13). Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21 acetoxypregn-9(11)-en-20-one (15), its 4-acetoxy derivative 16 and the 3,4 diacetoxy derivative 17. When tested in a radioreceptor assay in human mononuclear leukocytes the synthesized compounds showed only low relative binding affinities (RBA) to type 1 receptor, the highest being 0.72% for 13 (aldosterone = 100%). For comparison, other RBA in this system were: 19-noraldosterone, 20%; 18-deoxyaldosterone, 5.8%; 18-deoxy-19-noraldosterone, 4.7%; 18,21 anhydroaldosterone, 0.37%; 17-isoaldosterone, 7.6% and apoaldosterone, 4.3% PMID- 2268559 TI - Alkaline phosphatases and steroid receptors in human breast cancer. AB - Estrogen receptors (ER), progesterone receptors (PR) and alkaline phosphatases (AP) were measured in 150 tumors from patients who underwent mastectomy for primary breast cancer. The percentage of ER positive samples was inversely related to the AP activity ranging from 88.9% in low activity samples (less than 30 U/mg prot.) down to 30.6% in the high activity ones (greater than 400 U/mg prot.). When considering only ER positive samples, the ER content was inversely related to the AP activity. This could not be demonstrated for PR. Therefore, the authors suggest the hypothesis that in human breast cancer, the AP may play a role in the dephosphorylation of the ER molecule and in the consequent modulation of its binding capability. PMID- 2268560 TI - Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation. AB - The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent. PMID- 2268561 TI - Cortisol and cortisone production in rat and mouse adrenal incubations. AB - The presence of 17 alpha-hydroxylase in rodent adrenals is debated. The presence in blood of mice of 11-deoxycortisol together with the absence of cortisol is well known. We demonstrated here the in vitro synthesis of 17 alpha hydroxyprogesterone and cortisol from [3H]progesterone in rat and mouse adrenals. We have shown that these syntheses represented 45 and 28% of those of 11 deoxycorticosterone and corticosterone, respectively, from progesterone. These data clearly suggest the presence of a 17 alpha-hydroxylase activity in vitro in these rodents adrenals. In addition, a noticeable synthesis of cortisol (0.87 1.57% per mg tissue, i.e. 52-64% per incubation flask) from 11-deoxycortisol was also observed and was inhibited by 0.1-0.3 mumol of Metyrapone and SKF 12185. These results allow to underline that the adrenals of rat and mouse, two species commonly used in laboratory experiments, may be used for in vitro investigations on cortisol metabolism from exogenous radioactive precursors. PMID- 2268562 TI - Estrogen receptor binding characteristics of 1,11 beta-ethanoestradiol: effect of a 1,11 beta-bridge on steroidal estrogen. AB - As part of an ongoing program to develop high affinity estrogenic ligands we have synthesized the 11 beta-vinyl, 11 beta-ethyl- and 1,11 beta-ethanoestradiols. Because the 1,11 beta-ethano-estradiol had not been previously reported in the literature, the investigation of its receptor binding characteristics would provide valuable insight into the effect of 1/11 beta-substitution. The data obtained in this study indicate that although significant estrogen receptor affinity is present for the 1,11 beta-ethano derivative, the RBA values, 5-22.4%, were far less than those observed (5-300-fold less) for the corresponding 11 beta ethyl and 11 beta-vinyl estradiols and less than those for the 1-methyl and 11 beta-methyl estradiols. These results suggest that the orientation that the 11 beta-substituent must occupy is directed away from the A-ring and that substituents in the 1-11 pocket produce a detrimental effect on receptor interactions. PMID- 2268563 TI - In vivo conversion of norethisterone to ethynyloestradiol in perimenopausal women. AB - The extent to which norethisterone is converted to ethynyloestradiol is controversial. To investigate the conversion of norethisterone to ethynyloestradiol we have used a double isotope infusion technique to measure the conversion in vivo. The use of acids or bases was precluded to prevent possible artefactual formation of phenolic metabolites of norethisterone. Transfer constants for the conversion of norethisterone to ethynyloestradiol in two perimenopausal women were 2.26 and 2.34% as measured in blood and 2.27 and 0.38% in urine. Results from this study show that a small but significant proportion of norethisterone is converted to ethynyloestradiol in vivo. PMID- 2268564 TI - The pattern of measles in Ilorin. AB - A review of 598 cases of measles admitted to the University of Ilorin Teaching Hospital, (Nigeria) between January 1982 and December 1984, was undertaken. One hundred and fourteen children (19%) had measles by the age of nine months, and the number increased to 298 (49.8%) by 12 months of age. There were 207 (34.6%) cases during the second year of life and only 93 children second year of life and only 93 children (15.5%) were above two years of age. The most prevalent months for measles was found to be February, March and April, when 312 (52.29) of the cases occurred. Overall mortality was 71 (11.9%) with 58 (81.7%) deaths occurring among children two years and below. The commonest complications were bronchopneumonia and gastroenteritis with dehydration. Early immunization and further research, particularly into the optimum age for immunization is advocated. PMID- 2268565 TI - Ultrasound femur length as a means of assessing gestational age amongst Nigerians. AB - Foetal femur length values have been established with ultrasound amongst Nigeria pregnant women between 14-40 weeks of gestation. The growth of the femur describes an asymptotic curve similar to the one for biparietal diameter. A linear mathematical model was found suitable to describe the relationship between the femur length and gestational age and our values have been compared with those obtained from similar previous studies. The value of femur length data in gestational age assessment foetal weight estimation, and in the identification of foetal limb deformities is discussed. PMID- 2268566 TI - Tinea capitis in Awka local government area of Anambra State. AB - Between January and August 1984, a total of 1,555 Primary school children aged 4 18 years were surveyed for tinea capitis in Awka local government area of Anambra State, Nigeria. Specimens for mycological investigations were aseptically collected from 300 children showing evidence of tinea capitis and processed by standard method. A total of 158 (10.2%) mycologically proven cases of tinea capitis were detected. Prevalence of tinea capitis was higher in younger children (12.0%) aged 4-10 years than in older children (5.3%). Prevalence of 3.8% recorded for children over fifteen years of age. The species of dermatophytes Isolated were Microsporum audouini 38.0%, Trichophyton mentagrophytes (24%), Trichophyton soudanense (15%), Trichophyton tonsurans, (9%), Trichophyton Schoenlenii (9%) and Microsporum gypseum (5%). Overcrowding and poor sanitary living conditions were found to be factors favouring occurrance of tinea capitis in Awka local government area of Anambra State. PMID- 2268567 TI - Effect of host-diet inadequacy on the course of infection of plasmodium yoelii Nigeriensis. AB - Investigations were conducted into the course of infection of plasmodium yoelli nigeriensis in mice fed on an inadequate diet. It was found that mice fed on a '1/2' diet were able to withstand infection with the parasite better than mice fed on a full diet or a 1/4' diet. The haemoglobin value of mice fed on a full, '1/2' and '1/4' diets dropped by 67.5%, 66.8% and 68.8% respectively, while their Packed Cell Volume dropped by 27.1%, 28.9% and 31.2% respectively. No mortality was recorded for uninfected mice fed on a full diet and '1/2' diet throughout the duration of the experiment, although total mortality for the '1/4' diet group was recorded on day 14 after they were placed on the diet. PMID- 2268568 TI - Contraceptive choice in Lagos, Nigeria. AB - Among 1266 contraceptive acceptors (median age 30 years, median parity 4.5) attending a family planning clinic, mostly after referral from the post-natal clinic, two thirds chose the intrauterine device, almost all the remainder choosing oral contraception. Oral contraception was, however, the main choice among women parity 0 or 1. A definite intention to have no more children was given by none of the women of parity 3 or under, and only by 15% of those of parity 8 or more, so that child spacing was the main reason for accepting contraception. By 12 months, the discontinuation rate among oral contraceptive users was 17% (IUD 11%) of which 11% (IUD 6%) was for personal reasons or to plan pregnancy, 4% (IUD 5%) through adverse effects and 0.6% (IUD 0.8%) through accidental pregnancy. PMID- 2268569 TI - Diabetic ulcers--a clinical and bacteriological study. AB - In an 8 month period we have studied 100 consecutive patients with diabetic ulcers. The sex distribution was even. Eighty-three percent had non-insulin dependent diabetes mellitus. Sixty-nine percent of the ulcers were gangrenous as opposed to neuropathic and over half the ulcers involved the big toes. Osteomyclitis was seen in 44% of the patients. Staphylococcus aureus and Escherichia coli were the commonest infecting organisms at initial cultures and at repeat cultures 4 weeks later. Amoxicillin plus clavulinic acid (Augmentin) and Clindamycin were the best antimicrobial combinations in cases where the ulcers had some acute features (e.g. surrounding cellulitis). PMID- 2268570 TI - Chediak-Higashi syndrome: a report of two cases in African (Ghanaian) children. AB - Two cases of Chediac-Higashi Syndrome occurring in two African siblings are described. Both presented with the accelerated form of the disease and died. Only two previous cases occurring in blacks have been documented in the literature, emphasizing the rarity of this disease in Africans or those of African descent. PMID- 2268571 TI - Affective disorder and hyperthyroidism. Review and case report. AB - The presence of psychiatric symptoms in thyroid dysfunctions has long been recognised. The literature review shows that such presence is not common and often overlooked. A case seen and managed by both authors is presented. The benefit derived by such patients treated where access to several specialties are available is emphasised. PMID- 2268572 TI - Haematological values in pregnancy in Jos. AB - Blood samples taken from 270 women, 30 in first trimester of pregnancy, 90 in second trimester and 150 in third trimester, were analysed for haemoglobin (Hb) packed cell volume (pcv), white blood cell count (wbc) and differentials and platelet count. The values for 95%, range for first trimester was Hb 122 +/- 19.8, pcv .37 +/- .0568L/L, wbc 6.189 +/- 2.484 x 10(9)/L and platelet 200.428 +/ 101.828 x 10(9)/L, for the second trimester, Hb 117.5 +/- 25.2 g/L pcv .36 +/- .0706L/L, wbc 6.414 +/- 2.884 x 10(9)/L and platelet 189.168 +/- 101.828 x 10(9)/L, and for third trimester Hb 119.6 +/- 24 pcv .36 +/- .072L/L, wbc 7.119 +/- 2.356 x 10(9)/L and platelet 193.786 +/- 103.016 x 10(9)/L. These results were compared with those of 150 non-pregnant women whose haematological indices were Hb. 130.5 +/- 17.89g/L, pcv .3994 +/- .0716L/L, wbc 5.255 +/- 2.900 x 10(9)/L and platelet 242.600 +/- 105.416. These results show that there is a significant fall in Hb, pcv, and platelet in pregnancy, while wbc count shows a significant rise in pregnancy due to neutrophilia. PMID- 2268573 TI - Prevalence of intestinal parasitoses in relationship to diarrhoea among children in Ilorin. AB - Studies on the role of intestinal parasites in diarrhoeal disease in children were carried out among 907 children of one month to 120 months (10 years) of age both at out patients and inpatients in Unilorin Teaching Hospital. The most common intestinal parasites found were Ascaris lumbricoides (40.9%), Trichuris trichiura (27%), Hookworm (10.2%), Strongyloides stercoralis (9.7%), E. histolytica (6.3%), Trichomona vaginalis (2.8%). Taenia saginata (1.7%) and 1.1% of Paragonimus westermani, among the diarrhoeal cases. But among the non diarrhoeal group, intestinal parasites loads were lower, except Ascaris lumbricoides (58.2%). The main differences observed between the two groups was that the egg-load was higher among diarrhoeal than in non-diarrhoeal group. The role of parasites in the initiation of diarrhoea in children was discussed. PMID- 2268574 TI - Randomised comparative efficacy of clindamycin, metronidazole, and lincomycin, plus gentamicin in chronic suppurative otitis media. AB - Chronic suppurative otitis media is major health problem seen frequently in the ENT clinics in Nigeria and the outcome of most medical management in the past have been disappointing. A comparative randomised clinical trial involving combination therapies with systemic clindamycin, metronidazole, lincomycin, each with gentamicin, was conducted on a total of 14 patients. At the end of one week, and three-week, follow-up end points the clinical response with bacteriological cure were, for clindamycin and gentamicin 21%, metronidazole and gentamicin 33%, lincomycin and gentamicin 22%, and the control (aural toilet alone) 14%. However, when the clinical response was measured only by the ceasation of discharge, the outcome was more impressive. By this assessment the clinical response with clindamycin and gentamicin was 52% of the 140 patients, metronidazole and gentamicin 69%, lincomycin and gentamicin 47%, and the control 24%. The metronidazole and gentamicin regime was significantly more effective than the other regimes and it is suggested for use in prophylactic treatment of CSOM patients undergoing surgical procedures. PMID- 2268575 TI - Epidemiology of vesico--vaginal fistulae in northern Nigeria. AB - A comparative study of vesico-vaginal fistulae cases and controls was carried out at two tertiary hospitals in Maiduguri, Nigeria. The fistulae cases were significantly shorter in height, younger in age at marriage and had a higher divorce rate. Prolonged labour, traditional surgical practice of "gishiri cut" and ignorance were identified as the commonest causes of the fistulae. The health and socio-economic consequences to the patient are discussed. Patients are considered to have brought shame to themselves and their families and quite often lose the support of the husband. It is recommended that maternity services be firmly integrated and given a higher priority in primary health care. In the long term increase in the literacy level of females is desirable. PMID- 2268576 TI - Mapping of translocation breakpoints on the short arm of chromosome 19 in acute leukemias by in situ hybridization. AB - Non-random translocation involving the short arm of chromosome 19 are frequently observed in acute leukemias. Recent studies have shown that the 19p13 genes E2A and LYLl, both of which encode helix-loop-helix proteins, lie at two different translocation breakpoints in acute lymphoblastic leukemias (ALL). The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL. To assess the role of these genes in other leukemia-associated translocations we mapped their locations with respect to the t(11;19)(q23;p13) and t(4;19)(q21;p13) translocation breakpoints carried by T-ALL cell lines SUP-T13 and SUP-T8a, respectively. In situ hybridization studies indicated that the E2A and LYL1 genes are physically distinct from the t(4;19) and t(11;19) breakpoints. Using these and other 19p13 translocation breakpoints as landmarks, we established a partial physical map of 19p: 19pter-E2A-INSR-LYL1-[t(4;19)]-19cen. These data should help guide molecular studies to further characterize 19p13 breakpoints and mapping of genes in this chromosomal region. PMID- 2268577 TI - 1p13 is the most frequently involved band in structural chromosomal rearrangements in human breast cancer. AB - Cytogenetic data on 14 breast carcinomas were examined to determine which chromosome arms and bands are preferentially involved in structural chromosome changes. Chromosome arms 17p, 16q, and 1p and band 1p13 were found to be significantly involved. A review of the world literature confirmed 1p as being the most frequently involved arm in structural chromosome changes in breast cancer and 1p13 as being the band most frequently involved in such changes. The two sets of results were pooled, and the analysis of 113 tumours revealed 229 of 304 bands to be involved, with 1p13 affected in 20% of the tumours. PMID- 2268578 TI - Comparative cytogenetic analysis between cyclophosphamide-sensitive and resistant lines of acute myeloid leukemia in the Lewis Brown Norway hybrid rat. AB - An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F1 hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY-resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY sensitive and CY-resistant LBN AML lines. The CY-sensitive LBN AML cultures contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 41,XX,-1,-2, 9,del(12),del(20)(q13) + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11). The recently developed CY-resistant AML cells contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(3)(q36q42.1),del(4) (q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY-resistant line I [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent. PMID- 2268579 TI - Parallel karyotypic evolution and tumor progression in uterine leiomyoma. AB - Cytogenetic evidence of clonal evolution was detected in five uterine leiomyomas. In two tumors, two clones were found, the third tumor had four, the fourth had nine, and the fifth had 12 clones. The first tumor had trisomy 12 as the primary anomaly and a sideline that also contained a del(7)(q21q31). Both clones of the second tumor had three structural changes in common but differed by the presence in the more advanced clone of an inv(7)(q31q34). Two cytogenetically unrelated pairs of clones were seen in the third tumor. One clone had a stemline of 46 and an r(1); a sideline had developed through duplication of this clone. The other pair had a del(7)(q21q31) in common. The last two tumors both had t(12;14)(q14 15;q23-24) as the primary abnormality. They also had a high frequency of telomeric associations that involved certain chromosome arms only. One of the secondary changes in the fourth tumor was a del(7)(q21q31); the principal secondary change in the fifth case was a ring chromosome 1 of variable size in the different clones. The analysis of these five uterine leiomyomas and the collation of the results with previously obtained data lead us to conclude that del(7)(q21q31) is secondary to t(12;14) and + 12 in this tumor type, and that ring formation involving chromosome 1 material, often with duplication of segments, is a common phenomenon during clonal evolution. The fact that the tumors were classified as cellular and had an increased mitotic rate indicates a parallel development between histologically detectable tumor progression and cytogenetically recognizable clonal evolution in uterine leiomyomas. PMID- 2268580 TI - Irradiation microcell-mediated chromosome transfer (XMMCT): the generation of specific chromosomal arm deletions. AB - The microcell-mediated chromosome transfer technique has been used to introduce whole chromosomes into malignant cells and revert the tumorigenic phenotype. However, in most instances the limited availability of selectable chromosomes has hindered the ability to reduce the region containing the tumor suppressive information. The work presented here describes a new method to enrich for specific chromosomal arm deletions of selectable chromosomes and thereby more finely focus upon the genetic region of interest. The irradiation-microcell mediated chromosome transfer (XMMCT) technique involves the irradiation of microcells containing single human chromosomes followed by fusion to a nonirradiated host and cytogenetic characterization. The XMMCT procedure was performed on a microcell hybrid containing a der(11) as the only human chromosome. The resultant irradiated microcell hybrids were found to have deletions that ranged from simple interstitial deletions to complex deletions/rearrangements involving only the human der(11) chromosome. The XMMCT procedure has broad applications in generating chromosomal reagents for mapping genetic loci and for use in functional analyses such as tumor suppression studies. PMID- 2268581 TI - Breast cancer and other cancers in Norwegian families with ataxia-telangiectasia. AB - Patients who are homozygous for ataxia-telangiectasia (AT) have an exceptionally high incidence of cancer. Heterozygous individuals for the disease have been reported to be at an increased risk of cancer, particularly breast cancer in female carriers. We have analyzed eight Norwegian families with AT for cancer incidence in the parents, in the parents' sibs, grandparents, and grandparents' sibs. Two of the obligate heterozygote females have had premenopausal breast cancer. This incidence is significantly higher than expected for that group. No increase in the cancer incidence was observed in the parents' sibs, the grandparents, or the grandparents' sibs. Since the incidence of AT is low, data from many sources have to be combined to allow any conclusion. PMID- 2268582 TI - In situ hybridization ascertains the presence of a translocation t(6;11) in an acute monocytic leukemia. AB - In situ hybridization was performed in a case of acute monoblastic leukemia (FAB type M5b) with a rearrangement of the long arm of chromosome 11. Cytogenetic analysis after R- and G-banding showed an apparent deletion of 11q with a breakpoint at 11q23, and a translocation t(6;11) was suspected in certain metaphases. In situ hybridization with a biotinylated cosmid probe hybridizing at 11q25 confirmed the translocation t(6;11)(q27;q23). Use of nonradioactive in situ hybridization techniques for more precise characterization of chromosomal rearrangements in malignant cells is emphasized. PMID- 2268583 TI - Opportunities for more rational assessment of refractive corneal surgery. PMID- 2268584 TI - Intraocular lenses for the correction of myopia in phakic eyes: short-term success and long-term caution. PMID- 2268585 TI - The surgical treatment of high myopia: comparison of epikeratoplasty, keratomileusis and minus power anterior chamber lenses. AB - Seventy high myopic eyes (-8.00 to -28.00 diopters) with epikeratoplasty (n = 29), myopic non-freeze keratomileusis (n = 26) or minus power anterior chamber intraocular lenses in phakic eyes (n = 15) were operated by two surgeons and were evaluated retrospectively. Results are reported at the 6-month postoperative interval. Eyes treated with epikeratoplasty had an average preoperative spherical equivalent of the cycloplegic refraction of -17.80 D (range -12.00 to -28.00 D). At 6 months, 66.6% of eyes were within 3 D of emmetropia and 7.4% of eyes had an uncorrected visual acuity of 20/40 or more. Average preoperative spectacle visual acuity was 20/50 (0.39); it was 20/50 (0.37) at both 6 and 24 months. Between 6 and 24 months, 32.2% of eyes had a change in refraction of 1.00 D or more. Two lenticules were removed. Eyes treated with non-freeze keratomileusis had an average preoperative refraction of -10.0 D (range -8 to -15 D). At 6 months, 61.5% of eyes were within 3.00 D of emmetropia and 30.7% of eyes had an uncorrected visual acuity of 20/40 or better. Average preoperative spectacle visual acuity was 20/30 (0.67), and 6 and 12 months afterward it was 20/30-20/40 (0.57) and 20/30 (0.66) respectively. Between 6 and 12 months, 8.3% of eyes, had a change in refraction of 1.00 D or more. Eyes treated with minus power anterior chamber lenses had an average preoperative refraction of -17.30 D (range -12.50 to -20.00 D).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268587 TI - Proposed formula for the dioptric power evaluation of the posterior corneal surface. AB - The author performed mathematical calculations to determine the radius of the corneal posterior surface. Knowledge of this value can be used to accurately compute the intraocular lens power, especially in corneas modified by refractive surgery, such as keratomileusis or epikeratophakia. PMID- 2268586 TI - Comparison of minus power anterior chamber intraocular lenses and myopic epikeratoplasty in phakic eyes. AB - We performed a retrospective study of two sequential series of operations designed to correct high myopia in phakic eyes. The first series consisted of 21 eyes with refractive error ranging from -11.00 diopters to -21.00 D (mean -16.9 D). They received a commercially prepared, lyophilized, myopic epikeratoplasty lenticule sutured into a circular keratectomy. Seven lenticules had to be removed within the first year because of poor refractive results, corneal ulceration, or melting. The nine eyes followed from 12 to 24 months after surgery demonstrated residual refractive errors from +4.00 D to -11.25 D. We also studied an initial series of 41 eyes with preoperative myopia ranging from -9.00 D to -35.00 D (mean -15.00 D) that received a minus power anterior chamber intraocular lens. The lens had an open loop design with an anterior vault, four point angle fixation, and an optic diameter of 4.5 mm. Recovery of visual acuity was faster with the intraocular lens than with epikeratoplasty. Three intraocular lenses were removed; two because they were the wrong size and one because it was the wrong power. Two of the lenses were replaced with acceptable results. Of the 34 eyes followed for 12 months, all had a residual refractive error within +/- 2.00 D of emmetropia. During the short-term follow-up, no elevated intraocular pressure, cataract formation, or excessive endothelial damage was observed. We concluded that anterior chamber minus power intraocular lenses gave more rapid and predictable optical correction in high myopic eyes than did myopic epikeratoplasty. Longer follow-up is required before conclusions can be reached about the safety of these intraocular lenses. PMID- 2268588 TI - Draft clinical guidance for the preparation and contents of an Investigational Device Exemption (IDE) application for excimer laser devices used in ophthalmic surgery for myopic photorefractive keratectomy (PRK). Office of Device Evaluation, Division of Ophthalmic Devices, Food and Drug Administration. PMID- 2268589 TI - Light-induced maculopathy following epikeratoplasty. PMID- 2268590 TI - Bacterial endophthalmitis following postkeratoplasty relaxing incisions. PMID- 2268591 TI - Refractive microsurgery of the lens in high myopia. PMID- 2268592 TI - Problem cases in astigmatism following penetrating keratoplasty and hyperopic epikeratoplasty. PMID- 2268593 TI - The ophthalmic manifestations and treatment of the amniotic band syndrome. AB - The amniotic band syndrome is an unusual cause of craniofacial deformities. The syndrome, which is initiated by rupture of the amnion, results in an unpredictable combination of compression deformities of the fetus, construction or amputation defects of the extremities, and craniofacial clefting deformities. The type and extent of ophthalmic abnormalities are dependent on the band location and timing. They include a combination of bony orbital clefts or hypertelorism; lid anomalies such as colobomas, ptosis, and ectropion; lacrimal outflow obstruction; and globe involvement. We review the clinical course of 14 patients diagnosed with, or suspected as having, this syndrome and describe the methods of treatment. In most instances, multiple surgical procedures were required to restore function. Satisfactory cosmesis proved more difficult to obtain. PMID- 2268594 TI - Involutional entropion of the upper lid. AB - Involutional entropion is an inturning of the eyelid margin caused by changes of lid tissues due to aging. Two patients with the uncommon finding of involutional entropion of the upper lid were treated with surgery based on the principles used to treat common lower lid entropion. The causes of lower lid entropion include increased horizontal and vertical lid laxity, and correcting these same factors in the upper lid resulted in a satisfactory repair of the entropion. Treatment of involutional entropion in the upper lid is compared and contrasted with that of the lower lid. PMID- 2268595 TI - Mideyelid entropion. AB - A distinct entity of entropion involving the middle portion of the lower eyelids is presented. This condition is not related to any local or systemic disorder and does not progress to entropion of the entire lower eyelid. Segmental atrophy of the lower lid tarsus is present. PMID- 2268596 TI - Association of entropion with cataract surgery. AB - Ptosis may develop after cataract surgery because of a dehiscence of the levator aponeurosis. A series of patients undergoing entropion repair was examined in order to determine the mechanism of entropion and the correlation with cataract surgery. It is suggested that involutional senile entropion may develop related to cataract surgery, on the same basis as ptosis, due to disinsertion of the capsulopalpebral fascia. It is suggested that the cataract surgeon should examine the patient closely for preoperative entropion to prevent or anticipate the development of frank entropion after the cataract surgery. PMID- 2268597 TI - Medial palpebral tendon repair for medial ectropion of the lower eyelid. AB - The primary functional support for the medial eyelid is from the deep attachments of the orbicularis muscle to the posterior lacrimal crest and lacrimal diaphragm. A dehiscence of the deep medial canthal attachments can alter the position of the lower eyelid with subsequent tearing, medial ectropion, and ocular exposure. In this study, medial palpebral tendon reconstruction was performed on seven lower eyelids with medial instability or ectropion and a dehiscence of the medial palpebral tendon. A periosteal flap left attached to the posterior lacrimal crest was used to replace the attenuated or absent medial palpebral tendon. After a mean follow-up of 7 months, 86% (6/7) of the eyelids had acceptable cosmetic and functional results. The use of a periosteal flap to replace a dehiscence of the medial palpebral tendon has several advantages. The periosteal flap is readily available, strong, and autogenous. The lower eyelid and punctum are pulled tightly against the globe. Lastly, the procedure may be repeated or combined with other ectropion procedures. PMID- 2268598 TI - Cicatricial ectropion in lamellar ichthyosis. AB - A 35-year-old woman presented with bilateral lower lid ectropion associated with lamellar ichthyosis. She was successfully treated with postauricular skin grafts and horizontal lid shortenings. This report reviews the literature on the surgical management of this condition and suggests several modifications to prevent recurrence. PMID- 2268599 TI - The true canalicular angle: a mathematical model. AB - A mathematical formula that allows for the computation of the true angle between the upper and lower canaliculi using dacryocystograms is described. It was used to determine the true canalicular angle in 33 patients. The mean calculated angle at the 1.0 mm distance was 57.2 degrees +/- 13.0 degrees, and at the 0.5 mm distance was 65.2 degrees +/- 16.2 degrees. The true calculated angle was highly correlated with the angle measured in the Waters view. There was no statistically significant correlation between the right and left sides in the same patient. There was no statistically significant difference between the canalicular angle in males and females, and there was no correlation between canalicular angle and patient's age. A clinical application of this model is discussed. PMID- 2268600 TI - Canalicular laceration. An 11-year epidemiologic and clinical study. AB - From 1977 through 1987, a total of 222 patients (166 male and 56 female patients) underwent surgical repair of canalicular laceration at Wills Eye Hospital. Demographic and clinical information were collected from the medical records and by written questionnaire or telephone interview. Most injuries occurred in children or young adults (median age, 20 years). Overall, blows from fists was the most common cause of injury (52 patients, 23.4%). Dog bites or scratches were the most frequent causes among children. A total of 147 injuries (66.2%) involved the lower eyelid, 61 (27.5%) the upper eyelid, and 14 (6.3%) the upper and lower eyelids on the same side. Constant or stress epiphora occurred postoperatively significantly more often among patients with combined upper and lower canalicular injuries (61.5%) than among those with single canalicular laceration (19.7%) (p less than 0.01). Analysis with logistic regression showed epiphora to be more common among adults than children (p less than 0.05) when the pigtail probe had been used intraoperatively (p less than 0.05), or when no canalicular stent had been placed at the time of surgical repair (p less than 0.05). No statistically significant associations were found between sex, cause of injury, type of canalicular stent, or time interval from injury to surgical repair and presence of postoperative epiphora. PMID- 2268601 TI - The value of intranasal surgery in assuring the success of a conjunctivodacryocystorhinostomy. AB - Conjunctivodacryocystorhinostomy is a much maligned procedure, and there are widely varying opinions about its efficacy and long-term success. We present our modification of the procedure used in 38 eyes of 29 patients over 10 years, with an average follow-up of 2.5 years, which has resulted in a very high rate of success. PMID- 2268602 TI - Stevens-Johnson syndrome with associated nasolacrimal duct obstruction treated with dacryocystorhinostomy and Crawford silicone tube insertion. AB - Although Stevens-Johnson syndrome (SJS) has long been recognized as a cause of punctal and canalicular obstruction, nasolacrimal duct obstruction secondary to SJS is rare and has not been reported in the ophthalmologic literature. Keratoconjunctivitis sicca, entropion, and trichiasis are well-known complications of SJS that may require measures to supplement or preserve tears. Lacrimal drainage system obstruction may occasionally occur in the face of relatively normal tearing, resulting in clinically significant epiphora. We report two cases of SJS, one associated with epidemic keratoconjunctivitis, that led to nasolacrimal duct obstruction and canalicular obstruction or stenosis. Epiphora and, in one case, dacryocystitis, necessitated dacryocystorhinostomy and Crawford tube insertion. PMID- 2268603 TI - Nasal endoscopy in dye testing after dacryocystorhinostomy. AB - Dye testing with a nasal speculum and nasopharyngoscope was performed in 45 consecutive cases after dacryocystorhinostomy. Testing was positive in 60% of cases with a patent dacryocystorhinostomy when the nasal speculum alone was used to examine the nose. When the nasopharyngoscope was used, however, dye testing was positive in 98% of cases. In 2% of cases with a functioning dacryocystorhinostomy, the dye test was negative and the nasal ostium could not be visualized. The nasal ostium could not be visualized in 16% of cases because of severe nasal septal deviation or other nasal anatomic change. It is concluded that dye testing is a reliable measure of lacrimal drainage function after dacryocystorhinostomy when nasal endoscopy is performed and when the nasal ostium and surrounding nasal mucosa can be visualized. PMID- 2268604 TI - To staple or to sew... PMID- 2268605 TI - Surgical relations of the levator palpebrae superioris. PMID- 2268606 TI - Dermolipoma surgery, or, "an ounce of prevention is worth a pound of cure". AB - The surgery of dermolipoma is fraught with dangers. It too often is followed by damage to the lacrimal secretory system, intractable diplopia, blepharoptosis, and perhaps other undesirable complications. Since these tumors are benign, the smallest amount of surgery that debulks the tumor and leads to a cosmetically acceptable result is the best surgery for the patient's satisfaction and for the surgeon's peace of mind. By being aware of these factors, the surgeon can avoid most complications. Some methods of preventing and relieving the symptoms of potential complications of dermolipoma surgery are briefly considered. PMID- 2268607 TI - Irradiated homologous tarsal plate banking: a new alternative in eyelid reconstruction. Part I. Technique and animal research. AB - Reconstruction of full thickness eyelid defects requires the correction of both posterior lamella (tarsus, conjunctiva) and anterior lamella (skin, muscle). Tarsal substitutes including banked sclera, nasal cartilage, ear cartilage, and periosteum can be beneficial for posterior lamellar repair, while anterior lamellar replacement, including skin grafts, pedicle flaps, advancement flaps, etc., is important to cover the posterior reconstructed portion. At times, due to extensive tissue loss, the eyelid reconstruction can be particularly challenging. We have found an alternative posterior lamellar reconstructive technique utilizing irradiated homologous tarsal plate that can be particularly useful in selected cases of severe tissue loss. The experimental surgical procedure in monkeys and the histological fate of the implanted tarsus is described in Part I, and followed in Part II by our experience with this tissue in six human patients. PMID- 2268608 TI - Irradiated homologous tarsal plate banking: a new alternative in eyelid reconstruction. Part II. Human data. AB - Reconstruction of full thickness eyelid defects requires the correction of both posterior lamella (tarsus, conjunctiva) and anterior lamella (skin, muscle). Irradiated homologous tarsal plate provides a structured framework for the lid reconstruction, and is incorporated nicely into the normal lid anatomy. PMID- 2268609 TI - Lower eyelid reconstruction with an orbicularis oculi musculocutaneous transposition flap and a conchal cartilage graft. AB - A case of reconstruction of the lower eyelid with the combination of an orbicularis oculi musculocutaneous transposition flap as the covering flap and a free conchal cartilage graft as the lining is presented. It is believed that this combination gives an excellent result for the reconstruction of the medial portion of the lower eyelid in terms of features, form, function, and ease of reconstruction. PMID- 2268610 TI - The successful treatment of a divided nevus on a young patient using a modified Kunhnt-Szymanowski procedure. AB - A 16-year-old boy underwent excision of a congenital divided nevus on his left eyelids. The defect of the lower eyelid was repaired utilizing a modified Kuhnt Szymanowski procedure, and the part of the nevus on the upper eyelid was removed by simple horizontal excision and suture. The symmetry of both of his eyelids was successfully preserved without ectropion or conspicuous scars. This procedure is especially effective even in a young patient when removing a lesion extending to the lower ciliary border. PMID- 2268611 TI - Hypoglobus following orbital decompression for dysthyroid ophthalmopathy. AB - Hypoglobus following orbital decompression is not a rare complication. Hypoglobus requiring surgery to elevate the globe following orbital decompression is considered clinically significant hypoglobus. A retrospective analysis of 157 consecutive patients who had their orbits expanded by removing the medial wall and floor of the orbit found seven patients (4.5%) who required further surgery to elevate the globe. The seven patients who developed clinically significant hypoglobus following orbital decompression all developed a set of distinct clinical signs. These included a "setting sun" appearance of the globe, eyelid malposition, orbital volume loss, and strabismus. These clinical signs can be explained by the inferior movement of the globe and the orbital contents following the loss of support structures on the orbital floor. A two-wall orbital decompression performed on a cadaver reproduced the physical signs of hypoglobus. The dissection suggested that the periorbita is the most important structure supporting the globe in the orbit. PMID- 2268612 TI - Esotropia following bilateral lateral orbital decompressions for Graves' disease. AB - A 48-year-old woman with mild Graves' orbitopathy underwent bilateral lateral orbital decompressions through preauricular hairline incisions by a general plastic surgeon. Immediately postoperatively she developed marked left orbital and eyelid edema and incapacitating diplopia due to a large angle esotropia and severe bilateral abduction deficits. Examination 13 months later revealed normal visual acuities and a 90 prism diopter esotropia. She underwent complex strabismus surgery with resultant orthophoria in primary and down gaze. Four years later, a thin section computed tomographic scan revealed severe attenuation of both lateral rectus muscles with incarceration of the muscle bellies into the lateral osteotomy sites. This case demonstrates a rare, but avoidable, complication of orbital surgery for Graves' disease. PMID- 2268613 TI - Tear flow analysis through the upper and lower systems. AB - Using quantitative lacrimal scintillography, tear flow in the normal state was analyzed in 11 asymptomatic volunteers. The results were compared to states with the superior punctum occluded, and to those with the inferior punctum occluded. No significant difference in tear flow between the superior and inferior canaliculi was appreciated (P less than 0.05). Furthermore, no significant difference was noted in overall basal tear flow when one canaliculus was blocked compared to the patent system (P less than 0.05). This implies increased tear flow through the patent canaliculus when the opposite one is blocked. The clinical implications of these results are important in canaliculus repair after injury. PMID- 2268614 TI - Endoscopic repair of failed dacryocystorhinostomy. AB - Primary dacryocystorhinostomy (DCR) failure is commonly due to scarring at the rhinostomy site. Nasolacrimal duct obstruction due to scarring may also occur in patients who have had their lacrimal bone removed during maxillary sinus surgery. Five patients following DCR and 3 patients after sinus surgery, all with constant epiphora, underwent endoscopic reconstruction of their lacrimal drainage system. Preoperatively, patency of the bony ostium was determined either by computed tomographic (CT) scan or dacryocystography. Endoscopically, the lacrimal drainage system was reopened then intubated with a silastic stent. Any scar tissue was visualized endoscopically and resected. Seven of the 8 patients have been followed from 3 to 24 months after stent removal, and all have had relief of their epiphora. Endoscopic repair is a useful adjunct in the management of patients with DCR failure or patients with epiphora after removal of the lacrimal bone during sinus surgery. This brief procedure can be performed under local anesthesia, does not require a skin incision, and allows the evaluation and correction of intranasal pathology. PMID- 2268615 TI - New minitrephine makes lacrimal canalicular rehabilitation an office procedure. AB - A new minitrephine, with a stainless steel tube of 0.81-mm outer diameter, 16-mm length, a plastic hub and handle assembly for manual rotation, Luer lock attachment to either standard or specially designed 3-ml syringe with spring assisted plunger, and an intraluminal stylet--all disposable--has been designed by us principally for opening a distally occluded lacrimal canaliculus prior to stenting with any desired implant. Local anesthesia via a nasociliary nerve block makes this an office procedure. Other potential uses include transscleral globe biopsies of suspected malignancies, intraorbital biopsies, drainage of fluid filled spaces wherein a beveled needle evacuation might undesirably pierce the far end of the cyst--all with possible ultrasonic monitoring--or the creation of a correctly sized, round, noncollapsible passage for a Molteno valve stenting of the anterior chamber, for intractable glaucoma. PMID- 2268616 TI - Dacryocystorhinostomy in Wegener's granulomatosis. AB - Dacryocystorhinostomy was performed on two patients with Wegener's granulomatosis that had been quiescent for many years. Excellent results were attained, with elimination of dacryocystitis, complete relief from epiphora, and maintenance of a patent outflow tract. No wound necrosis occurred postoperatively, in contrast to a previous report in the literature. Our experience suggests that nasolacrimal duct obstruction in the setting of quiescent Wegener's granulomatosis can be treated safely and effectively with dacryocystorhinostomy. PMID- 2268617 TI - Force necessary to fracture the orbital floor. AB - Current thought on the pathophysiology of orbital wall fractures postulates either a "hydraulic" or a "buckling" mechanism. Evidence from cadaver, dried skull, and theoretical model studies supports both theories. No in vivo data, human or nonhuman primate, are available that quantitate the force necessary to fracture the orbital floor by either of the two mechanisms. We developed an apparatus that delivers quantifiable force only to the globe, without occluding the orbital opening or striking the orbital rim. We used it on 11 anesthetized Macaca fascicularis monkeys. Following a single bilateral application, the orbits were exenterated, and the orbital walls and orbital contents were examined to determine the extent of injuries. Fractures were described, diagrammed, and photographed. Fracture of the orbital floor was consistently produced at and above a force of 2.08 J. Posterior ruptures of five eyes occurred over the same range. We provide the first accurate measurements of the force required to produce orbital blow-out fractures in a live primate model. We show that orbital floor fractures can occur at low energies with direct ocular trauma only ("pure" hydraulic mechanism). Orbital wall fractures failed to protect the globe from rupture in 23% of cases. PMID- 2268618 TI - Inferior rectus muscle entrapped by Teflon implant after orbital floor fracture repair. AB - A patient with a tripod fracture had entrapment of the inferior rectus muscle after reconstruction of an orbital floor defect with an alloplastic implant. Prior to insertion of the implant, the operating surgeon reported no motility disturbance. An orbital computed tomography scan suggested that the implant impinged on the inferior rectus muscle. Because of persistent diplopia, the orbit was reexplored. An intraoperative forced duction test prior to removal of the implant was positive in the field of action of the inferior rectus muscle. An intraoperative forced duction test after removal of the implant was negative in the field of action of the inferior rectus muscle. Motility was markedly improved after removal of the implant. These findings confirm that the implant was the cause of the entrapment. The surgical technique utilized to minimize complications after orbital floor reconstruction with the implant is outlined in this article. PMID- 2268619 TI - Isolated blow-in fracture of the lateral orbit causing globe rupture. AB - A blow-in fracture is a less common consequence of orbital trauma. Fragments of orbital bone may increase the orbital pressure, causing direct or indirect damage to the globe. This paper describes a blow-in fracture where a bone fragment perforated the globe causing globe disorganization and necessitating enucleation. PMID- 2268620 TI - The paranoid patient: surgeon beware! AB - Patients who have a paranoid disorder have a general expectation of being exploited or harmed. Assessment of personality and mental health is an important aspect of the preoperative patient evaluation. Paranoid patients can be troublesome or even physically dangerous, but may be difficult to detect preoperatively. We recount our experiences with such a patient and suggestions are made for detecting these patients and managing them. Care should be taken to avoid cosmetic facial surgery on such patients. PMID- 2268621 TI - A program to find regions of similarity between homologous protein sequences using dot-matrix analysis. AB - MATRIX is a program designed primarily to enable the user to visualize all regions of similarity between two proteins at a glance. The program helps the user to see where they are similar--at what relative positions in the amino acid sequences of the two proteins in question does the similarity exist; how they are similar--what functional characteristics the two similar sequences have in common; and to what extent they are similar--is the similarity significant, if so how significant relative to other similar sequences in the protein. This is achieved by constructing a diagram in which quantitative parameters of amino acids are used to compare every amino acid residue of the first protein with every amino acid residue of the second. Another function of the program is, given two sets of atomic coordinates--either of different proteins or for the same protein (for self-comparison)--to demonstrate which residues of the two proteins, when the two proteins are superimposed upon each other, appear in the same space (or are close to each other). PMID- 2268622 TI - A real-time malleable molecular surface. AB - We describe a method for generating a molecular surface using a parametric patch representation. Unlike previous methods, this algorithm generates a parametric patch surface which is smooth and G continuous and manipulable in real-time. Crucial to our approach is the creation of a net of approximately equilateral triangles from which we generate the control points used as the basis for describing the surface. We present in detail the method used for generating the triangular net and accompanying control points, along with examples of the resulting surfaces. PMID- 2268623 TI - A two-path recursive relational database structure for molecular information systems. AB - A recursive relational database structure, called the two-path structure, is proposed for holding data about the properties and structure of molecules. The two-path database approach solves certain severe restriction problems by providing two pathways to the structure of complex chemical entities. One pathway permits a fast descent to the atomic structure in terms of correct IUPAC carbon atom occurrence numbers. The other pathway descends through the molecular substructures, which can be referenced at any level in retrievals. The database appears to be capable of faithfully recording the structure of all chemical entities, including proteins and enzymes. PMID- 2268624 TI - Making video presentations from the Evans and Sutherland PS390. AB - The presentation of 3-dimensional and dynamic molecular information is often impaired by the use of conventional static display media. This paper explains a simple procedure for the direct capture onto video of graphical output from the Evans and Sutherland PS390 display. A technique for the integration of molecular images with supplementary textual and graphical information provided by commercial video titling software is also explained. We have found such presentation techniques to be of particular value in both the presentation of research results and in the preparation of material for use in a teaching environment. PMID- 2268625 TI - Chem-Ray: a molecular graphics program featuring an umbra and penumbra shadowing routine. AB - Chem-Ray, new molecular graphics program, utilizes a combination of standard algorithms developed for molecular systems as well as various ray casting techniques to produce highly realistic images on inexpensive raster terminals. The program produces images of space-filling, ball and stick or stick models derived from a user-supplied coordinate list. The most notable new feature of Chem-Ray is a simple, yet effective, algorithm for the improved treatment of shadows within a molecule. This new algorithm is based upon a calculation of a light pyramid at each point under examination. Intersections of various objects with this light pyramid will decrease the percentage of the light that can reach the point. If the entire cross-section is blocked, the point will be in the umbra of the shadow; if only a portion of the light is blocked, the point will be in the penumbra of the shadow. PMID- 2268626 TI - PCDRA: PC interactive molecular representation and modeling system. AB - PCDRA was designed to provide the average biologist with a user-friendly molecular display on a low-cost personal computer. The package is menu driven and is built so that a biologist, with little or no computing knowledge, finds it easy to use. The system gives a color representation with depth cueing of a protein whose atomic coordinates are stored as a PDB file. Moreover, the system presents several features similar to HYDRA and therefore is a good introduction to molecular graphics, especially for beginners in protein modeling. PMID- 2268628 TI - WHAT IF: a molecular modeling and drug design program. AB - A FORTRAN 77 computer program has been written to aid with macromolecular modeling and drug design. Called WHAT IF, it provides an intelligent and flexible environment for displaying, manipulating, and analyzing small molecules, proteins, nucleic acids, and their interactions. A relational protein structure database is incorporated to be queried. The program is suitable for most common crystallographic work. The menu-driven operation of WHAT IF, combined with the use of default values wherever user input is required, makes it very easy to use for a novice user while keeping full flexibility for more sophisticated studies. Although there are not too many unique features in WHAT IF, the fact that everything is integrated in one program makes it a unique tool for many purposes. PMID- 2268627 TI - Calculation of binding energies using a robust molecular mechanics technique: application to an antibody-antigen complex. AB - A novel molecular mechanics technique, which is both computationally efficient and robust, for calculation of relative stability of macromolecules and binding energies is presented. The technique delivers exact results for a number of hypothetical systems; the technique can be used to energy minimize a number of similar macromolecules simultaneously; simultaneous minimization of many structures requires computer time only fractionally over that needed to energy minimize one such structure. The method has been used to successfully calculate the relative stability and binding of two avian lysozymes to the monoclonal antibody D1.3. PMID- 2268629 TI - [Clinical studies of the proper indication of inlay and crown therapy in lateral tooth areas]. AB - 187 students were examined an epidemiological study for their dental conditions and requirements with respect to preservation and prosthetics. The persons tested showed a DMF-T index of 11.6 and a DMF-S index of 24.2 in the lateral tooth area. In our opinion the clinical investigation revealed that the total number of caries cases will rise three-fold due to the above-average frequency of secondary caries cases as the filling size (or the number of filling surfaces) increases. The amount of single crown dentures found in the lateral tooth area with 0.1 crowns per person tested turned out to be fairly low. The actual need for a tooth preserving therapy concept by crowning in preference to the concept of filling therapy amounts to the twelve-fold of the existing single crown dentures. PMID- 2268630 TI - [Amalgam as restorative material--state of the art]. PMID- 2268631 TI - [Dental amalgam--filling material with future?]. AB - On the basis of a literature survey there is a discussion about advantage and disadvantage of dental amalgam, possible alternatives and at least eventual dangers by intoxication of mercury. As result the amalgam were found without hesitation and classified as clinical suitable. PMID- 2268632 TI - [Epidemiological profile of dental caries and treatment needs]. AB - In a population survey 2,263 patients were examined for their caries status and treatment needs. The DMF/T-Index and the individual relative risk for caries were calculated. Adolescents and young adults showed a high caries risk and required most of all necessary restorations. But especially older adults and seniors over 55 years presented a high caries risk, required more extensive restorations and more public dental health care at all. PMID- 2268633 TI - [Examination of the mechanical workability of biocompatible ceramics]. AB - Biocompatible ceramics++were tested with various methods of technical treatments for an eventual employment in a mechanical work process. The material is distinguished for grinding, dividing and polishing, there is an possibility of form grinding with diamond disks. The correction of surfaces by the polish with customary methods. It is not necessary to etch surfaces for use of retention after form grinding. PMID- 2268634 TI - [Clinical controlled trial for secondary caries preventive effect of Duraphat on cavity walls]. AB - On a base of a clinical controlled trial the secondary caries preventive effect of a topical application of fluoride varnish (Duraphat) was verified. 255 pairs of amalgam restorations were placed in 191 patients, 152 (79.6%) of whom returned for assessment after a 24 month follow-up period. This group of 152 patients received 188 (73.7%) pairs of restorations. The cavity walls of one restoration of each pair were covered with an thin layer of a fluoride containing varnish. The secondary caries rate of the untreated restorations in such manner was four time greater than the treated ones. The results suggest that the topical application of a fluoride varnish on the cavity walls can be an effective measure for secondary caries prevention. PMID- 2268635 TI - [Investigations of cytotoxicity of Heliosit depending on its polymerizing in vitro]. AB - In this paper the authors describe the changing in cell culture of epithelioid cells of a permanent HEp-2-line basing on the one component composite Heliosit. Following the experiences with farmer test the authors mean that contact and local toxicity are not so heavy but depending from the polymerization of the materials. Warning is the arretation of some phases in cell cyclus and the changing of epithelioid cells in fibroblastoid cells. May it is a cell transformation necessary to examine in special tests. PMID- 2268637 TI - [Prosthetic treatment of children and adolescents]. PMID- 2268636 TI - [Therapy of fractured crown of juvenile permanent tooth]. AB - Above all the treatment of fractured juvenile frontal teeth doesn't represent a restoration problem but a problem of conservation of the tooth. In cases of uncomplicated crown-fractures the covering of all opened dentin tubuli must be recommended. In complicated crown-fractures the method of partial pulpotomy is preferred instead of pulp amputation regarding special indication. A closed cooperation with the orthodontist should be in the treatment of juvenile frontal teeth with a vital pulp. PMID- 2268638 TI - [Clearance rate of gingiva and content of collagen of inflammated and clinically non-inflammated papilla interdentalis]. AB - The gingiva vessel function has been defined by gingivitis (A), clinical sound gingiva without (B) and with loss in attachment (C) as well as the collagen fraction by biopsy material. The division of the probands at the age between 20 and 24 years into groups has been carried out after checking the SBI, PII (Silness/Loe) and the loss of attachment of the teeth 43-33. The vessel function has been found out through the impulse rate of the gingiva Xenon-133-clearance by calculating the clearance rates (CR) (groups: A1 n = 15; B1 n = 18; C1 n = 16). The vestibular interdental papillae have been elaborated in a second study for finding out the collagen fractions with the Stegemann method modified by Woessner (groups: A2 n = 18; B2 n = 10; C2 n = 12). The statistical reliability has been checked by the t-test (F-test) and the u-test by Mann and Whitney. RESULTS: In the clearance study the CR in group A1 are higher and in group C1 lower than in group B1. In the second study the increased collagen solubility in group A2 by inflammation is confirmed, in group C2 a significant higher share in unsoluble collagen and total collagen has been defined than in group B2. PMID- 2268639 TI - [Effects of a conservative stomatological treatment on central and peripheral stress parameters and the influence of a beta-adrenergic blocking agent]. AB - Under conservative stomatological treatment the behaviour of peripheral stress parameters is investigated in connection with an estimation of the subjective state of health as well as for the first time in the ambulatory stomatology the STH secretion as an expression of a central stress reaction. The possibility of the central nervous as well as cardiovascular influence by an unusual premedication form of the beta-adrenergic blocking agent "Obsidan" is estimated in various stages of treatment in comparison to a placebo application. PMID- 2268640 TI - [Etiology of pathologic abrasions under special consideration of anorexia nervosa]. AB - Various factors can be cause the origin of pathologic abrasions. A rare cause is the psychosomatic disease "Anorexia nervosa". Dependent on the etiology the clinical symptoms of abrasions are differently. The author describes these symptoms and the treatment in a case of "Anorexia nervosa". PMID- 2268641 TI - [Fluoride content of deciduous teeth after regular intake of black tea]. AB - Continuous intake of black tea rich in fluorides leads to distinct increase of fluoride content of temporary teeth. This is to consider analogous a caries prophylaxis. PMID- 2268642 TI - [Oral Streptococci - a scheme for the identification of Streptococcus mutans]. AB - A reliable simple scheme for the rapid identification of certain species of oral streptococci has been developed and compared with biochemical and physiological results of 45 well known clinical isolates and stock strains. Moreover, a method for the determination of H2O2 production was tested. With selected reactions as for instance acid formation in mannitol and raffinose broth, hydrolysis of arginine and esculin, the production of peroxidase, and the resistance of bacitracin the species S. rattus, S. sobrinus, S. mutans, S. cricetus, S. ferus, S. milleri, S. mitis, S. sanguis, S. mitior, and S. salivarius were differentiated. PMID- 2268643 TI - [Measurement of epidemiological facts in dentistry]. AB - Recent epidemiological investigations about caries report about phenomenons like "caries increase" or "caries decline". This kind of observation bases on prevalence-studies. But describing such phenomenons does not give the opportunity to explain the observations. For that purpose the modern methodology of epidemiology should be used. Despite of the fact that epidemiology differs exactly between incident and prevalent cases, the use of incidence studies seems to be extremely seldom in stomatology. This paper discusses the problems, which occur in incidence-studies about caries and especially in cohort-studies. The authors show the difficulties to adopt terms like incidence density and cumulative incidence to studies about caries. A proposal is given in order to adopt the modern methodology of epidemiology to the special problem of caries. PMID- 2268644 TI - [Experimental investigations about the influence of the gnathological force on the results of the tracing pin registration]. AB - With the help of video- and computer techniques is investigated in what respect the forces operating in intraoral tracing pin registration have an influence on the mandibular movement at the sagittal plane. The results significantly show this dependence. PMID- 2268645 TI - [Linear model of the etiology of temporomandibular pain dysfunction syndrome]. AB - The investigation searched if a relatively complete, empirically tested model of the etiology of the mandibular dysfunction can be set up. The so-called LISREL- (Linear Structural Relationship) method was used for statistic evaluation. All factors showing a direct connection with the anamnestic and clinical dysfunction index were built into the model. The results led to the conclusion that anxiety and constitutional joint factors also play a role in the occurrence of mandibular dysfunction. The most important etiological factors are given by malocclusions, by occlusal interferences, impaired general state of health and parafunctions. PMID- 2268646 TI - [Reduced mastication as a cause of chronic gastritis]. AB - The influence of reduced mastication on the pathogenesis of chronic gastritis was examined in rats. In spite of reducing experimentally the masticatory effect to a third no inflammation of the gastric mucosa was to provoke. Nevertheless, the attended group showed a significant smaller increase of weight during the experiment. PMID- 2268647 TI - [Old problem--contribution to hygienic exhaustion of dental technician working places]. AB - The work hygienical limit rates are exceeded without a exhaustion at the working place. An exhaustion device is required. For solution of the problem a technical possibility is represented. PMID- 2268648 TI - [Prosthetic education in Germany and perspectives on harmony in the European community]. PMID- 2268649 TI - [Systematic procedures in endodontics]. AB - Endodontic treatment is an important part in operative dentistry. While quantity of treatment increases, the quality should not be neglected. Means to improve the individual success rate are shown in the article. The simplification of the armamentarium and systematics of procedures are of utmost importance. As the basic technique the hand instrumentation is described. PMID- 2268650 TI - Day surgery: is it the way to go? AB - This article will identify the change in ophthalmology nursing practice which occurred at St. Boniface General Hospital (Winnipeg, Manitoba). The discussion will begin with a review of the benefits of day surgery and will then describe the ophthalmology day surgery program. The formal evaluation results will be reviewed. The article will provide nursing administrators with an overview of an ophthalmology day surgery program and will demonstrate day surgery's potential use in other institutional settings. PMID- 2268651 TI - Family-centered maternity care: the nursing administrator's role. AB - The author contends that nursing administrators can and should take a leadership role in making family-centred maternity care a reality everywhere in Canada. Two Canadian surveys have revealed that many hospital maternity practices which fall within nursing's domain are outdated. Furthermore, these practices mitigate against the development of confidence and mastery in the new family. The trend towards a shorter length of stay for obstetrical patients makes the implementation of FCMC more essential now than ever. The article outlines the nursing administrator's role in supporting and promoting family-centered maternity care. The characteristics of this approach are outlined and the components of a quality assurance programme to achieve it are provided. Attitudes of the nursing staff and ways of overcoming resistance and "selling" family centred maternity care are described. Finally, an example which illustrates typical obstacles to implementing a family-centred approach is presented for analysis. PMID- 2268652 TI - Clinical nursing research and quality assurance: integration for improved patient care. AB - Understanding how nursing quality assurance and research programs are similar, yet different, is the first step towards enabling nurse managers to integrate the two programs. Blending research findings and research methods into the quality assurance process is one method of accomplishing integration. Other strategies include setting standards for nursing research and including instruments with known validity and reliability in patient care planning and patient assessment. Improving the scientific basis of nursing practice and the quality of patient care are viable outcomes. PMID- 2268654 TI - Nursing management 2000. PMID- 2268653 TI - The one minute nursing manager. PMID- 2268655 TI - From nursing to nursing administration: making the transition easier. AB - When nurses get involved in nursing administration, they may experience difficulties with the managerial role. There are several reasons why these difficulties occur: failure to recognize that the skills required for management are different than those required for nursing; refusing to "let go" of former nursing duties; inconsistent emphasis on the development of managerial capability among nursing supervisors; and insufficient formal training in management. Suggestions for making the transition to management easier are presented. These include developing the proper mix of skills for management; delegating authority properly; systematizing on-the-job-training for supervisors; and restructuring the formal academic preparation that nurses receive while in B.N. programs. PMID- 2268656 TI - Nursing research organizational models. AB - Nursing departments have a responsibility to promote nursing research activities. To attain this goal, they may select and/or adapt an organizational approach from existing models for nursing research. Research consortium, directorate, program, group, and single researcher, organizational models are described and discussed in this paper using examples from the literature and current practice. Issues which nurse administrators and researchers should consider when selecting and implementing organizational models are presented. These include the departmental perspective regarding nursing research, the nurse researcher role, and compatibility between model and departmental characteristics. PMID- 2268657 TI - Satisfaction with nursing workload systems: report of a survey of Canadian hospitals. Part A. AB - Senior nursing executives from a representative sample of Canadian hospitals were surveyed on their attitudes and views of nursing workload measurement systems. In terms of a profile of users and their satisfaction, the survey found that about 50% of hospitals were using a system, and that among those using a system, 70% used information from the system frequently or all the time. The senior nurse respondents were generally satisfied with their current systems; slightly lower levels of satisfaction were reported for staff nurses, with the most common objection being the perception that the systems do not reflect true workload. A subsequent article--Part B--explores senior nurse executives' needs and expectations for nursing workload systems. PMID- 2268658 TI - Satisfaction with nursing workload systems: report of a survey of Canadian hospitals. Part B. PMID- 2268659 TI - The environment--ours to consider. PMID- 2268660 TI - Developing a rationale and recruitment plan for a nurse researcher. AB - Hospital administrators are becoming more aware of the valuable contribution of nursing research to the provision of quality nursing care. Research provides objective and tested information on which to base crucial decisions regarding patient care and the wise use of scarce health care resources. A systematic approach used to define the need for, and to prepare a comprehensive proposal for the recruitment of a nurse researcher is outlined. The process described in this article can be applied to the creation of any new position in the health care system. PMID- 2268661 TI - The professional nurse: with or without a uniform. AB - Nurses are not united in their view about the symbolic and practical importance of the nurses' cap and uniform. Controversy about manditory dress codes for nurses still exists in many agencies and institutions. The uniformed nurse can evoke positive and negative images, ranging from the angel of mercy and handmaiden of the physician, to the inflictor of pain. Nurses seek greater autonomy over their work life, and more say about matters that affect them. Nurse administrators are in a key position to take the lead in promoting practices that assist nurses to assume responsibility for many aspects of their professional lives. This paper explores the origin of the nurses uniform and cap and their continued relevance for modern nurses. PMID- 2268662 TI - Nurses' perspectives of quality work environments. PMID- 2268663 TI - Evaluating the competence of clinical nurses from beginning to advanced practitioner. AB - Frequently, clinically competent nurses leave direct patient care for non clinical positions or other careers to achieve greater professional advancement and recognition. The drain of clinical nursing expertise away from the patient prompted the development and evaluation of a clinical promotion program to appraise and recognize clinical nursing competence. At the beginning of the evaluation period, 205 nurses were appraised for clinical competence and categorized as: Level 1--a beginning practitioner or a nurse returning to service; Level 2--a skilled clinical practitioner; and Level 3--an advanced clinical practitioner. Nurses volunteered information related to demographic characteristics, education, clinical experience, and attitudes to their work and work environment. Reassessments were completed after one year. Evaluation of the program employed a longitudinal comparative design. The major finding shows significant shift in clinical nurses' competence over time with a greater percentage of nurses at higher levels of ability. Further evaluation of the program is in process. PMID- 2268664 TI - Asking questions. PMID- 2268665 TI - Organizational support of the clinical nurse specialist role: a nursing research and professional development directorate. AB - Administrative support is essential for optimal utilization of the Clinical Nurse Specialist (CNS) resource. It has been linked to successful role implementation, role efficacy and job satisfaction. The article addresses how a Nursing Research and Professional Development Directorate (NRPD) provides administrative support of the CNS role. The impact of the directorate on the role functions of practitioner, consultant, educator and researcher is delineated. Specific challenges to the CNS role and organizational benefits are described. A model of organizational support of the CNS, based on the concepts of collaboration and peer mentorship, is proposed. The model emphasizes mutual goal setting to achieve both organizational and professional objectives. PMID- 2268666 TI - The topography of bovine beta-casein at an oil/water interface as determined from the kinetics of trypsin-catalysed hydrolysis. AB - The topography of bovine beta-casein at a soya oil/water interface was studied by following the kinetics of the trypsin-catalysed hydrolysis. Tryptic peptides were identified from their amino acid compositions and the kinetics were compared with those obtained from beta-casein in solution. Whereas soluble beta-casein was initially hydrolysed at a number of trypsin-sensitive bonds, the hydrolysis of the protein at the interface was a more ordered event. The crucial initiating step was the cleavage of the N-terminal peptides 1-25 and 1-28 from the molecule. Hydrolysis at other trypsin-sensitive sites could then occur. This suggests that with the exception of the large hydrophilic moiety in the N-terminal region, most of the beta-casein molecule is inaccessible to the proteinase, and lies fairly flat on the oil/water interface. After removal of the N-terminal peptide, the remaining macropeptide can reorientate and other hydrophilic regions become accessible to the proteinase. PMID- 2268667 TI - Conformational plasticity of butyrylcholinesterase as revealed by high pressure experiments. AB - The ligand binding and kinetic behaviour of butyrylcholinesterase (EC 3.1.1.8, acylcholine acylhydrolase) from human plasma was studied at 35 degrees C under high hydrostatic pressure. The binding of phenyltrimethylammonium was studied by affinity electrophoresis at various pressures ranging from 10(-3) to 2 kbar. The kinetics of enzyme carbamylation with N-methyl(7-dimethylcarbamoxy)quinolinium iodide was studied in single-turnover conditions up to 1.2 kbar using a high pressure stopped-flow fluorimeter. Experiments were carried out in different media: 1 mM Tris-HCl (pH 8) with water, water containing 0.1 M lithium chloride and deuterium oxide as solvents. The volume changes (delta V and delta V++) associated with each process were determined from the pressure-dependence of the binding and kinetic constants. Kinetic data show that the binding of substrate to the enzyme leads to a pressure-sensitive enzyme conformational state which cannot accomplish the catalytic act. The pressure-induced inhibitory effect is highly cooperative; it depends on both the nature (charged or neutral) and the concentration of the substrate. Also, large solvent effects indicate that enzyme sensitivity to pressure depends on the solvent structure. This findings suggests that the substrate-dependent pressure effect is modulated by the solvation state of the enzyme. PMID- 2268668 TI - Human red cell acid phosphatase: purification and properties of the A, B and C isozymes. AB - Human red cell acid phosphatase isozymes encoded by three alleles (ACP1*A, ACPI*B and ACP1*C), each of which generates two isozymes, (f) and (s), were purified to homogeneity. The molecular mass of the six isozymes (Af, As, Bf, Bs, Cf and Cs) was estimated to be 17-18 kDa, the mass of the f isozymes probably being slightly higher than that of the s isozymes. It was indicated that the isozymes react with p-nitrophenyl phosphate in the mono anionic state, and that a group with a pKa value of about 6, which may be histidine, is of importance for the catalytic function of the s isozymes. Significant differences between the f and s isozymes were observed with respect to specific activity. Km (p-nitrophenyl phosphate), Ki (p-aminobenzylphosphonic acid), amino acid composition, stability in the presence of urea, thermal stability, retention time in size-exclusion chromatography of the native isozymes and migration in sodium dodecyl sulphate polyacrylamide gel electrophoresis, In contrast, identical or similar properties were observed for the three genetically different f isozymes, and the same was the case for the three s isozymes. It is suggested that the f and s isozymes serve different functions in the cell. PMID- 2268669 TI - Proton nuclear magnetic resonance study of human interleukin 6: chemical modifications and partial spectral assignments for the aromatic residues. AB - Partial assignments for the 1H-NMR resonances of the aromatic residues in human interleukin 6 (IL-6) are reported. The homonuclear Hartmann-Hahn spectrum clearly shows all connectivities for the histidine, tyrosine and tryptophan residues that exist in IL-6. Using a deuterium exchange method, the imidazole proton resonances of His-16 and His-165 have been assigned. Iodination of the tyrosine residues led to the assignment of Tyr-32. Photo-chemically induced dynamic nuclear polarization data have shown that His-16, Tyr-32 and Trp-158 are exposed to solvent, whereas His-165, Tyr-98 and Tyr-101 are buried. Iodination of Tyr-32 gave no significant effect on IL-6 activity, suggesting that Tyr-32 is not responsible for IL-6 activity. PMID- 2268670 TI - Functional and NMR studies of Hb Sassari (Asp-126 alpha----His); role of the inter-subunit contacts in the affinity control of human hemoglobin. AB - The oxygen affinity of hemoglobin Sassari (Asp-126 alpha----His), a variant substituted in the alpha 1 beta 1 interface, was found to be 8-times greater relative to normal adult human hemoglobin. Study of the exchangeable hydrogen bonded protons by NMR spectroscopy shows only minor changes at the alpha 1 beta 1 interface. In particular, the resonance previously assigned to the proton of the hydrogen bond Asp-126 alpha 1. . . Tyr-35 beta 1 in normal hemoglobin is still present in the variant spectrum, suggesting that His-126 alpha can also form a hydrogen bond with the Tyr-35 beta. The possible explanation of the increased affinity of hemoglobin Sassari and other variants substituted in the same structural region is discussed in terms of perturbations of the equilibrium between the two quaternary states. PMID- 2268672 TI - Conformational changes of human serum albumin in vivo induced by free fatty acids as studied by Fourier transform infrared spectroscopy. AB - Binding of free fatty acids (FFA) to human serum albumin (HSA) was studied by Fourier transform infrared (FT-IR) spectroscopy. Six volunteers ran a marathon race in order to induce changes in their basal plasma FFA levels. Three volunteers were well-trained and three untrained. The non-deconvolved HSA spectra show two types of spectra: the first one includes the untrained runners, who, after the run, display noticeable changes in the absorbance intensity of the amide I band, which also shifts to higher frequencies. The second one includes the well-trained subjects who exhibit few changes after the race. Examination of the deconvolved spectra of HSA shows two types of spectra, as well: the first class displays important decreases in the absorbance of the component assigned to alpha-helix after the race, together with a gradual growth of the two components that can be assigned to turns. The second class, which includes the well-trained subjects, exhibits few changes after the run. These data are interpreted in terms of conformational changes due to a less ordered alpha-helix state of HSA after FFA binding, while the emergence of components assigned to turns may reflect the exposure of several histidine residues to the solvent (which are buried in HSA when FFA/HSA less than 4). Our data are consistent with the Karush model of FFA to HSA binding. PMID- 2268671 TI - An exploration of the binding site of aldolase using N-(omega-hydroxyalkyl) glycolamidobisphosphoric esters. AB - N-(omega-Hydroxyalkyl)glycolamidobisphosphoric esters (P-O-CH2-CO-NH-(CH2)n -O P), which are analogues of the aldolase (D-fructose-1,6-bisphosphate D glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) substrate fructose 1,6 bisphosphate, were synthesized and used for probing its active site. These phosphate compounds competitively inhibited aldolase activity. The Ki value was lowest when the maximum distance between the phosphorus atoms of the bisphosphate was brought close to that of fructose 1,6-bisphosphate. The inhibitor constants, Ki, were compared to those of alkanediol monoglycolate bisphosphoric esters and alkanediol bisphosphate compounds, which were reported previously by Ogata et al. The values of Ki for the bisphosphate compounds containing an amide group, the amide bisphosphate compounds, were smaller than those for the bisphosphate compounds containing an ester group, the ester bisphosphate compounds, and those for alkanediol bisphosphates were the largest for the same distance between phosphorus atoms in these bisphosphates. The difference spectra of aldolase caused by binding of a saturating concentration of N-(omega hydroxypropyl)glycolamidobisphosphoric ester resembled that of butanediol monoglycolate bisphosphoric ester. However, the effects of the amide bisphosphate compounds on the absorption spectrum of aldolase were smaller than those of the ester bisphosphate compounds for the same distance between phosphorus atoms in these bisphosphate compounds. These results suggest that the synthesized phosphate compounds bind to aldolase at the active site and the -CO-NH- group of the compounds might be held more tightly than the -CO-O- group by hydrogen bonds, presumably with the amino acid residues in the active site, such as Lys-146 or 229 and Asp-33 or Glu-187. On the other hand, the -CO-O- group might be more effective in changing the environment of the Trp-147 residue in the active site of this enzyme. PMID- 2268673 TI - Boar transition protein 2 and 4 isolated from late spermatid nuclei by high performance liquid chromatography. AB - The boar late spermatid nuclei retaining transition proteins (TPs) could be obtained from the testis by the use of antipain to inhibit TP-degrading proteinases of the nuclei. The enzymes detected in acid extract including the basic proteins were inactivated by reduction and carboxymethylation of the proteins. The reduced and carboxymethylated basic proteins were fractionated by differential precipitation between 3% trichloroacetic acid (TCA) and 3-20% TCA. From the 3% TCA-precipitate, boar TP2 and TP4 were isolated by high-performance liquid chromatography (HPLC) on Nucleosil 300 7C18. The two TPs were characterized by acid urea- and SDS-polyacrylamide gel electrophoreses and amino acid analysis. Boar TP2 closely resembled rat and mouse TP2s, and ram protein 3 in its high content of serine and basic amino acids, the presence of cysteine and molecular weight. Boar TP4 was similar to ram protein P1 in its high content of basic amino acids, the presence of cysteine and molecular weight. But the TP2 and TP4 differed in electrophoretic mobility on acid urea-gel and solubility in 3% TCA from those of the other species. The HPLC used here also enabled us to efficiently separate boar TP1, TP2, TP3 and TP4, and to estimate that the amount of the TP2, TP3 and TP4 was about 1/8, 1/4 and 1/4 that of the TP1, respectively. PMID- 2268674 TI - 'Chymotrypsin-like' activity of chicken liver multicatalytic proteinase resides in the smallest subunit. AB - Chicken liver multicatalytic proteinase is composed of multiple components with molecular masses ranging from 23 to 34 kDa and has 'chymotrypsin-like' and 'trypsin-like' activities, which were examined by using the chromogenic peptide substrates, succinyl-Phe-Leu-Phe-pNA(p-nitroanilide) and N-benzoyl-Phe-Val-Arg pNA, respectively. Treatment of the enzyme with diisopropyl fluorophosphate (DFP) completely abolished the 'chymotrypsin-like' activity, but had little effect on the 'trypsin-like' activity. In the experiment with radio-labeled DFP, SDS-PAGE of the modified enzyme revealed that the radioactivity was incorporated into only the smallest subunit (23 kDa). The migration of this subunit was retarded on SDS PAGE after the treatment with DFP. PMID- 2268675 TI - Self-association of diisopropylphosphoryl-alpha-chymotrypsin: the involvement of active site of the enzyme in its self-association behaviour. AB - The self-association of diisopropylphosphoryl(DIP)-alpha-chymotrypsin is studied in order to find out whether the active site of the enzyme is involved in its self-association behaviour or not. Sedimentation coefficient as well as the weight-average (Archibald) molecular weight data are obtained as a function of concentration using an analytical ultracentrifugation technique. The analysis indicated that the experimental data fits the model of indefinite self association. The comparison of the data with earlier data on alpha-chymotrypsin revealed that after the modification at the active site, the association constant for the self-association is reduced by about 47%, and the system deviated from ideality. Results showed further that Ser-195, at the active site, appears to be involved in the self-association behaviour of alpha-chymotrypsin; however, the participation of other groups at the active site is also implicated. PMID- 2268676 TI - Isolation and sequence of an active-site peptide from maize leaf phosphoenolpyruvate carboxylase inactivated by pyridoxal 5'-phosphate. AB - An active-site peptide from maize (Zea mays L.) phosphoenolpyruvate carboxylase has been isolated, sequenced and identified in the primary structure following chemical modification/inactivation of the enzyme by pyridoxal 5'-phosphate and reduction with sodium borohydride. The amino acid sequence of the purified dodecapeptide is Val-Gly-Tyr-Ser-Asp-Ser-Gly-L*ys-Asp-Ala-Gly-Arg, which corresponds exactly to residues 599-610 in the deduced primary sequence of the maize-leaf enzyme. Comparative analysis of the deduced amino acid sequences of the enzyme from Escherichia coli, Anacystis nidulans and C3, C4 and Crassulacean acid metabolism plants indicates that they all contain this specific lysyl group, as well as a high degree of sequence homology flanking this species-invariant residue. This observation suggests a critical role for Lys-606 during catalysis by maize phosphoenolpyruvate carboxylase. This represents the first identification of a specific, species-invariant active-site residue in the enzyme. PMID- 2268677 TI - Fluorescence studies with potato carboxypeptidase inhibitor. AB - Potato carboxypeptidase inhibitor (CPI) is a 39-residue globular protein whose X ray structure is known. The protein's two tryptophan residues (W22 and W28) appear to be on the surface in the crystal structure. The fluorescence spectrum of CPI has a maximum at 344 nm. Acrylamide solute quenching yields an upward curving Stern-Volmer plot with KSV approximately 9 M-1. KI quenching yields a linear plot with KSV approximately 5.5 M-1. These studies indicate that emission occurs from a solvent exposed residue(s). Fluorescence lifetime measurements were fitted to a biexponential decay law with tau 1 = 0.9 ns. f1 = 0.22 and tau 2 = 3.9 ns. Anisotropy decay data were described by a single rotational correlation time of 1.2 ns. This value is somewhat small for the global rotation of a protein of this size. The low temperature phosphorescence of CPI shows a biexponential decay, with a rapidly decaying 0.5-1.0 second component. The triplet state of at least one of the two tryptophan residues must be perturbed by interaction with nearby disulfide bonds. PMID- 2268678 TI - Neutral surface aminopeptidase activity of human tumor cell lines. AB - Seven human tumor cell lines were studied for their neutral surface aminopeptidase (AP) activity. The activity was shown to exist on all cell lines to varying degrees. The neutral AP activity of the cell lines had similar Km values and were affected by the same inhibitors as those reported for AP's of peripheral blood lymphocytes (PBL, Refs. 1 and 2). However, a difference was seen in the Vmax values of the various cell lines. These values were shown to correlate (r = 0.767, P less than 0.05) with cell surface area. PMID- 2268679 TI - Structural aspects of pathology in Alzheimer's disease. AB - The characteristic lesions of Alzheimer's disease, neurofibrillary tangles and neuritic plaques, are the sites of accumulation of abnormal fibrillar material. The structure of the paired helical filament from tangles has been analysed by electron microscopy and biochemical studies have shown that it contains microtubule associated protein tau as a component. Fibrils of beta-amyloid in the neuritic plaque arise by polymerization of a small proteolytic fragment of a much larger precursor protein. It is not yet clear what triggers the events that lead to assembly of the abnormal structures nor why the structures once formed are so resistant to turnover. PMID- 2268680 TI - Molecular interactions between HIV and the T lymphocyte. PMID- 2268681 TI - Homology of the B50 murine melanoma antigen to the Ro/SS-A antigen of human systemic lupus erythematosus and to calcium-binding proteins. AB - B50 is a murine melanoma-associated antigen found in tight association with B700, a melanoma-specific antigen. B700-like molecules are produced by all melanomas tested to date, including those of murine, human, swine and hamster origin. We have used rabbit antibodies to B50 to determine whether B50 expression is also restricted to melanomas. The results demonstrate that B50 is a commonly occurring protein, or is immunologically cross-reactive to a commonly occurring protein; 29 of 29 cell lines tested bound anti-B50 antibodies. N-terminal amino acid sequence analysis indicates that B50 has significant homology to the Ro/SS-A antigen of human systemic lupus erythematosus and to calcium binding proteins; hence B50 is likely to be an RNA and/or calcium-binding protein. PMID- 2268682 TI - Molecular heterogeneity in McArdle's disease. AB - Biopsies were taken from a group of eleven patients with McArdle's disease, a congenital deficiency in muscle glycogen phosphorylase. The biopsies were screened by Western and Northern blotting for phosphorylase protein, phosphorylase-bound pyridoxal-5'-phosphate (the cofactor of the enzyme) and for phosphorylase mRNA. Of the eleven patients, three expressed phosphorylase mRNA at near normal levels and at the expected size. One of these patients also expressed low levels of phosphorylase protein that correlated with a small amount of measurable phosphorylase activity. These data support the contention of molecular heterogeneity in the presentation of this phenotype. PMID- 2268683 TI - Human erythrocyte Band-3 has an altered N terminus in malaria-resistant Melanesian ovalocytosis. AB - There is a high prevalence of the erythrocyte polymorphism ovalocytosis associated with reduced susceptibility to malaria in Papua New Guinea. The major erythrocyte integral membrane protein, Band-3, showed markedly increased phosphorylation in whole cells or isolated ghosts from ovalocytic individuals. The cytoplasmic domain of the ovalocyte Band-3 was found to be approx. 3 kDa larger than the normocytic protein. The N-terminal sequence of the ovalocytic Band-3 was different from the reported sequence for human Band-3, suggesting that the increased size results from an N-terminal extension. Since this is the region of Band-3 which is phosphorylated and interacts with the red cell cytoskeleton, it is likely that this alteration in ovalocytic Band-3 is the underlying cause of the diverse alterations in ovalocytic cells including increased phosphorylation, increased membrane rigidity, decreased agglutinability by blood group antibodies and refractoriness to invasion by malarial parasites. PMID- 2268684 TI - C1q, a collagen-like complement subcomponent, in dermatosparactic cattle: its extracellular modification is not affected by lack of procollagen N-terminal proteinase (pN-proteinase). AB - C1q, a collagen-like complement protein, was purified from the serum of a dermatosparactic calf which lacks procollagen N-terminal proteinase (pN proteinase). The specific hemolytic activity of the serum C1q from the dermatosparactic animal was identical to that of C1q from a normal calf. Gel filtration of serum from the dermatosparactic calf, on Sepharose 6B, showed the presence of C1q-antigenic material at only one position which was identical to the elution position of normal bovine C1q. No difference, under dissociating conditions, could be seen in the size of the chains of C1q in specific immunoprecipitates isolated from the sera of dermatosparactic and normal animals, as judged by polyacrylamidegel electrophoresis (PAGE) in the presence of sodium dodecyl sulfate (SDS). The C1q from the dermatosparactic animal showed the same N terminal amino acid and tryptic-digest peptide pattern on HPLC as C1q from the normal calf. These results strongly suggest that pN-proteinase is not involved in the extracellular processing of C1q. PMID- 2268685 TI - Hemoglobin Calais [beta 76 (E20) Ala----Pro]: a hemoglobin variant with decreased intrinsic oxygen affinity. AB - Hb Calais [beta 76 (E20) Ala----Pro] is a new human hemoglobin variant displaying a decreased oxygen affinity. The only electrophoretical difference with Hb A was a slightly more acidic isoelectric point. A 2-fold decrease in the oxygen affinity was found by equilibrium measurements performed in a suspension of intact red blood cells and in the lysate. It was confirmed by kinetic studies of the purified abnormal hemoglobin. The rate of methemoglobin formation at 37 degrees C of Hb Calais was also increased relative to Hb A. The mechanism by which the Pro for Ala substitution of an external residue in the beta-chains results in these profound functional abnormalities is unclear. Subtle changes at the heme pocket, at a distance from the mutation, may be a plausible explanation for the effects observed. PMID- 2268686 TI - Comparable interaction of doxorubicin with various acidic phospholipids results in changes of lipid order and dynamics. AB - We have characterized the interaction of the antitumor drug doxorubicin with model membranes of the anionic phospholipids dioleoylphosphatidic acid (DOPA), dioleoylphosphatidylserine (DOPS), cardiolipin and dioleoylphosphatidylglycerol (DOPG) as compared to the zwitterionic dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylethanolamine (DOPE). The saturating binding levels were: 2.4 (DOPA), 1.3 (cardiolipin), 1.5 (DOPS, DOPG) and 0.02 (DOPC) doxorubicin per lipid phosphorus (mol/mol). The half-saturating free drug concentrations were comparable for DOPA, cardiolipin, DOPS and DOPG: 20, 16, 35 and 18 microM, respectively. Doxorubicin fluorescence revealed the simultaneous existence of at least two populations of bound drug in the various anionic phospholipids: (1) fluorescent molecules with chromophores that reside between the lipid molecules and (2) above 0.01-0.02 doxorubicin bound per lipid phosphorus: non-fluorescent drug-stacks that are closer to the aqueous phase than the fluorescent molecules. Small-angle X-ray scattering indicated that doxorubicin can reorganize anionic phospholipid dispersions into closely-packed multilamellar structures. Addition of the drug caused leakage of entrapped 6-carboxyfluorescein. Neither 2H-NMR on [2-2H]serine-labelled DOPS nor 31P-NMR revealed any significant effect of doxorubicin on headgroup conformation, but 2H-NMR on di[11,11-2H2]oleoyl-labelled phospholipids showed that the drug had a strong acyl chain-disordering effect on anionic phospholipids. 2H-NMR relaxation measurements indicated that the drug immobilized the headgroups and acyl chains of anionic phospholipids. The implications of these observations for the cellular activity of the drug are indicated. PMID- 2268687 TI - Psychiatry down under. PMID- 2268688 TI - Observations on the metabolism of the psychotomimetic indolealkylamines: implications for future clinical studies. AB - Although the psychotomimetic indolealkylamines N,N-dimethyltryptamine, 5-methoxy N,N-dimethyltryptamine, and 5-hydroxy-N,N-dimethyltryptamine have been unequivocally identified in human body fluids, evidence relating their concentration to the presence of psychotic illness in humans remains controversial. A series of studies on the metabolism of the compounds in the rat have highlighted the rapidity and with which these are metabolized and renally excreted. The implications of our observation for the interpretation of past clinical studies and the design of future ones is discussed. PMID- 2268689 TI - Treatment effects of alprazolam and imipramine: physiological versus subjective changes in patients with generalized anxiety disorder. AB - The correspondence between changes in physiological activity and somatic symptom reports was assessed in generalized anxiety disorder patients treated with alprazolam or imipramine. After 6 weeks, the two medications produced comparable reductions in self-reported somatic symptoms. However, patients taking alprazolam showed decreases in systolic blood pressure, epinephrine, and norepinephrine, and patients taking imipramine showed increases in heart rate, blood pressure, electromyographic activity, and norepinephrine. Thus, though the physiological changes associated with alprazolam treatment were consistent with changes in symptom reports, treatment with imipramine produced a desynchrony: patients reported significant decreases in cardiovascular symptoms and muscle tension in spite of the fact that heart rate, blood pressure, and electromyographic activity increased. Possible explanations for this counterintuitive phenomenon are discussed. PMID- 2268690 TI - A. E. Bennett Award paper. Adrenocortical function, social rank, and personality among wild baboons. PMID- 2268691 TI - Ontogeny of selective attention effects on event-related potentials in attention deficit hyperactivity disorder and normal boys. AB - A longitudinal study of young attention-deficit hyperactivity disorder (ADHD) boys has found clear evidence for developmental abnormalities in event-related potential (ERP) waves that reflect cognitive processes associated with selective attentional tasks. Boys alternated attention to auditory or visual modalities in a train of stimuli, in an attempt to detect target stimuli in the attended modality. Results suggest that ADHD boys' attentional difficulties are due to insufficient facilitation of responses to the attended stimuli and not to an inability to block ignored stimuli. Abnormalities in ERPs reflecting cognitive processes associated with both interchannel selection mechanisms (processing negativity) and intrachannel selection mechanisms (P3b) were found. The degree of abnormality in the P3b responses to target stimuli in ADHD boys (lower than normal boys) was found to increase with age. It is suggested that the abnormally low P36 response to attended target stimuli found in ADHD boys may be due in part to insufficient LC noradrenergic activity normally triggered by attended task relevant or novel stimuli. PMID- 2268692 TI - Prostaglandin E2 levels in cerebrospinal fluid of normal and narcoleptic dogs. AB - It has been shown that endogenous prostaglandin D2 and prostaglandin E2 (PGE2) are involved in sleep-wake regulation. Our recent experimental result that exogenously administered PGE2 significantly reduces canine cataplexy (a pathological equivalent of rapid-eye-movement sleep atonia and a symptom of narcolepsy) suggests that PGE2 is involved in the pathophysiology of canine narcolepsy. In order to further investigate the role of prostaglandins (PGs) in this disorder, PG levels in cerebrospinal fluid (CSF) of genetically homozygous narcoleptic, heterozygous (unaffected), and control Doberman pinschers were studied. PGE2 levels were measured by direct radioimmunoassay (RIA) and after high-grade purification using PG affinity columns and high-performance liquid chromatography. PGD2 and PGF2 alpha levels were measured by RIA after high-grade purification. There was no significant difference in PGE2 levels between homozygous narcoleptic and heterozygous or controls dogs, and PGD2 and PGF2 alpha levels were undetectable in most cases. Our results do not favor the hypothesis that central PGE2 levels are modified in canine narcolepsy, assuming that PGE2 levels in cisternal CSF properly reflect PGE2 production in the brain. PMID- 2268693 TI - Minute-by-minute analysis of REM sleep timing in major depression. AB - Sleep changes described in depressed patients may represent alterations in the timing of rapid-eye-movement (REM) sleep or sleep onset. We examined these variables in groups of healthy control subjects (n = 47), depressed outpatients (n = 98), and depressed inpatients (n = 41). Outpatient depressives had greater severity of clinical symptoms than inpatients using the Hamilton Rating Scale for Depression. The depressed inpatient group had a later mean sleep onset time than the other groups, and the depressed outpatient group had a wider range of good night times than control subjects. REM timing in each group was examined as a relative frequency distribution of REM sleep (FDRS) for each minute across the night. The FDRSs for the three groups were statistically compared using the parameters from a two-component model, which includes a deterministic sinusoidal function and a time series process for errors. The slope of the linear trend in the FDRS rhythm was smaller (less positive) for both depressed groups than for controls. The ultradian FDRS rhythm occurred at an earlier phase, relative to sleep onset, in the inpatient depressed group compared to the control group. The ultradian FDRS rhythm had a longer period in the outpatient group compared to the control and inpatient groups. When referenced to 24-hr clock time in an exploratory analysis, the depressed groups appeared to have less robust FDRS ultradian rhythms than controls, but they did not appear to have a systematic phase alteration compared to controls. Abnormalities of REM sleep timing in groups of depressed patients may reflect a disturbance of sleep initiation and generation, or difficulty in entrainment of REM, rather than a systematic phase alteration in REM sleep propensity. PMID- 2268694 TI - Exploration of the atherosclerotic plaque. AB - During the past 3 decades we have achieved a better understanding of the atherosclerotic process. It has been described as a series of changes in the intima of arteries consisting of the focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissues, and calcium that are also associated with changes in the media. The process begins with a vascular injury that is complicated by the deposition of cholesterol esters and cholesterol. It is followed by the accumulation of lipid ladened monocytes as well as the initiation of immune mechanisms. The proliferation of smooth muscle cells into the lesion assures its permanence by the synthesis of fibrous tissue. Platelet aggregation, thrombosis and hemorrhage are all key components of plaque progression, that ultimately are associated with vascular occlusion and focal vascular spasm. Calcium plays an important role in the development of hard, ulcerated lesions. Atherosclerotic risk factors are believed to accelerate the progression of atherosclerotic plaques and the control of these risk factors may retard their proliferation and progression. PMID- 2268695 TI - Chest pain. AB - The accurate diagnosis of chest pain is often difficult. We review the differential diagnosis of chest pain and the diagnostic studies used in the evaluation of chest pain syndromes. Myocardial ischemia, aortic dissection, pulmonary embolism, pericarditis, and gastroenterologic sources of chest pain are the most common. The chest X-ray, electrocardiogram, echocardiogram, heart catheterization studies, and esophageal studies are helpful diagnostically. PMID- 2268696 TI - Proliferative activity, lectin-dependent and natural cytotoxicity in blood, lymph node and spleen from patients with Hodgkin's disease. AB - Mononuclear cells and T-lymphocytes of the blood, spleen and lymph nodes from 48 patients with Hodgkin disease (HD) and blood donors were tested in assays for lectin-dependent (LD) and natural killer (NK) cytotoxic activity. On average, peripheral blood T cell lectin-dependent cytotoxicity differs from that of the donors. However, cytotoxic activity appears to be dependent on the stage of disease; in the IY stage LD cytotoxicity was decreased 2-fold. The lectin dependent cytotoxicity was also dependent on the histological type of disease and the lowest level (50% of the control level) was associated with the lymphoid depletion type. The cytotoxic activity of T-lymphocytes from the affected areas of the patients' spleen was more marked than that of the unaffected areas. Spleen cell cytotoxicity showed no other correlations. Cytotoxicity of lymphocytes from the affected lymph nodes was drastically lower than activity of blood and spleen lymphocytes. NK activity of the patients' blood and spleen lymphocytes was twice as low as the control level (healthy donors) and did not correlate with stage and/or histological type of disease. The proliferative activity of lymphocytes from 33 HD patients was tested in vitro using allogeneic mononuclear cells from healthy donors or HD patients and/or PHA as stimulators. The response of patients' lymphocytes to alloantigens appeared to be much less affected than response to polyclonal mitogen. Thus, the results obtained by us demonstrate signs of stimulation of the lymphoid system against a background of general immunosuppression in HD. PMID- 2268697 TI - Rising cholesterol levels in children with familial hypercholesterolaemia. AB - Reference ranges (5th to 95th percentile) for fasting total serum cholesterol concentration were calculated for 571 unrelated children aged 4-19 years, without known predisposition to hypercholesterolaemia. Values were 3.31-5.81 mmol.l-1 for boys and 3.20-5.66 mmol.l-1 for girls, without significant differences between sexes at any age, compared to our laboratory reference ranges for men (3.46-6.87 mmol.l-1) and women (3.00-6.38 mmol.l-1). A further 85 children, each with a first degree relative with Familial Hypercholesterolaemia (FH), were studied. Initially, 39 had high cholesterol concentrations suggestive of FH. Repeated serial measurements were carried out in 18 of the 46 apparently unaffected children. Seven of these showed marked increases in serum cholesterol over 1-7 years, reaching concentrations above the 95th centiles of the appropriate reference ranges. The annual rate of increase was significantly higher than in the 11 who remained normocholesterolaemic. In 3 of these 7 children, diagnosis of FH was confirmed retrospectively, using recombinant DNA technology to show that each had inherited the defective allele of the LDL-receptor gene from an affected parent. Thus, serial cholesterol measurements may be needed to confirm or exclude FH in potential heterozygotes, while DNA studies can be used for definitive diagnosis in some families. PMID- 2268698 TI - [Effects of enkephalins on associative processes of parietal cortex neurons]. AB - Experiments on cats examined the effect of met- and leu-enkephalins on the process of learning of the parietal associative cortex neurons (field 5). It has been shown that conditioned electrical stimulation of the pyramidal tract axons with nociceptive reinforcement evoked plastic changes of responses in 35 neurons. It was found that the effect of microiontophoretically applied enkephalins on these neurons depend on the time of iontophoretic application. When endogenous opioid peptides were applied up to 30-40 min they inhibited the process of elaboration of temporary connection. PMID- 2268699 TI - [Afferent connections of the nuclei of dorsal columns of spinal cord]. AB - The authors studied structural origins of the conduction of the dorsal chord afferent projections to contralateral dorsal column nucleus in cats, which were discovered after foreleg electrical stimulation by the evoked responses method. This evoked responses remain after unilateral section of the medial lemniscus. It was shown the existence of not classical connections which cross to another side at the level of spinal cord and caudal division of brain stem. The discovery fibres contact with other projection systems and form all known types of interneuronal contacts. PMID- 2268700 TI - [Significance of refractory period in the method of counter flows]. AB - The results of model tests accomplished for precision and evaluation of present restrictions in the collision method are demonstrated in this work. The reduction of induced antidromic potential due to its "collision" takes place in the interelectrode area. This fact is of a great importance for the use of the collision method as it increases probable encounters of anti- and orthodromic impulses and possible intervals between stimulation and exploring electrodes. PMID- 2268702 TI - [Effects of the decrease of hydrodynamic resistance of a solution on response of cerebral arteries in perfusion]. AB - Acute experiments on isolated segments of carotid arteries of cats and on human middle cerebral arteries have demonstrated the narrowing effect (15-18%) during the perfusion with solution of polymer with extraordinary lengthy (WSR-301, USA) in concentration of 2.10(-6) g/ml. Effects were doze- and endothelial dependent. It has been established that arteries responded to minor changes in experiments with the increase of the fluid flow (from 15 to 40 ml/min). It may be concluded that the diminishing of arteries reaction in the presence of polymer solution depended on the drug reduction polymer influence on shear stress, and changing of angio-hemo relationships. PMID- 2268701 TI - [Distribution of labeled amino acids and delta-sleep inducing peptide in the body after instillation into the conjunctiva of the rabbit eye]. AB - Dynamics of 3H-valine, 3H-glycine and 3H-DSIP distribution in various brain structures, tissues and liquids of an organism due to administration of these substances in eye conjunctive were studied in rabbits with scintillation spectrometry method. Marked amino acids and DSIP were observed in all substrates in 10 min after administration. Maximal activity was found in 2 h in the brain visual cortex and in 30 min in cardiac tissue, spleen and optical chiasma. PMID- 2268703 TI - [Comparative characteristics of epileptic syndromes induced by kindling electrostimulation of limbic structures with 24-28 hour and 5 minute intervals]. AB - The experiments were conducted on rabbits with chronical electrode implants 2 weeks after the implantation. Animals were divided into 4 groups. It was established that in animals with rapid kindling the duration of motor seizures was longer, the generalization of spiking in the brain structures was significantly lesser. Postictal refractory period for these animal groups was inhibited to a marked degree. Our data showed that the inhibition of postictal refractory period and facilitation of motor seizures in the case of rapid kindling cannot be explained only by weakening of antiepileptic mechanisms. PMID- 2268704 TI - [Effects of difenin on experimental parkinsonian syndrome]. AB - The aim of this study was to investigate the effect of difenin on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesis and rigidity followed by the high amplitude slow and rapid waves in the CN and in sensorimotor cortex (SC). The changes of the electrical activity in the CN were more prominent then in SC. I.p. injection of difenin (20 mg/kg) resulted in an increase of motor activity and decrease of rigidity in rats. The reduction of extrapyramidal symptoms were correlated with at the inhibition of GPEE in the CN. These data suggest that difenin can be a part of the complex pathogenetic therapy of parkinsonian syndrome. PMID- 2268705 TI - [Effects of adaptation to exposure to short-term stress on indices of resistance of energy metabolism and contractile function of the myocardium to acute hypoxic hypoxia and reoxygenation]. AB - Effect of preliminary adaptation to immobilization stress with progressive duration from 15 min. to 1 h (every second day, 8 sessions) on the resistance of indices of myocardial energy metabolism and contractile function to acute hypoxic hypoxia and subsequent reoxygenation was studied. It was shown, that adaptation to short-term stress exposure by some way provided the retention of activities of important enzymes like creatine-phosphokinase and phosphorylase under the harmful action of acute hypoxia and subsequent reoxygenation. At the same time, the ATP restoration and the CP super-restoration were observed during reoxygenation. This effect, in its turn, was accompanied by a more pronounced super-restoration of the heart contractile function than in control. PMID- 2268706 TI - [Possible mechanisms of anti-ulcer action of silatranes]. AB - A stimulating effect of methylethyl(silatrane-I-ilmethyl)-sulphonium iodides, 1 (ethoxy)silatranes and 1-(chloromethyl)silatrane on the processes of rat test acetate ulcer healing is studied. Silatranes efficiency is not inferior to oxyferriscorbone and exceeds that of methacil. It is shown that all preparations inhibit the processes of lipids peroxidation in the blood, in liposomes and stomach tissue. PMID- 2268707 TI - [Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity]. AB - The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine. PMID- 2268708 TI - [Effects of phospholipase A2 on the etiology of pulmonary edema hemodynamics of lesser circulation in intact and vagotomized animals]. AB - In experiments on white rats, guinea pigs and cats it was shown that intravenous infusion of phospholipase A2 (FLA2) caused the development of pulmonary edema (PE) in guinea pigs, but did not cause it in rats and cats. Bilateral vagotomy on the neck led to the appearance of the expressed edemogenous effect of FLA2 on the lungs. Pentobarbital anesthesia decreased the effect of vagotomy. This effect is not connected with the turn off of the efferent impulsation in vagus nerves as the infusion of atropine did not repeat the influence of vagotomy. Authors assume that the action of FLA2 is realized across the secretion of humoral factor in vagotomized animals and the increase of the permeability of the aero-hematic barrier. PMID- 2268709 TI - [Comparative physico-chemical characteristics of trophoblastic beta-1 glycoprotein preparations isolated from retroplacental blood]. AB - Trophoblastic beta 1-glycoprotein preparations (TBG-1, TBG-2) isolated by different methods preserve their physicochemical and immunochemical properties. According to the data of disk-electrophoresis and densitometry TBG-1 preparation obtained using two-stage method is highly purified and protein yield is about 20%, while TBG-2 isolated by multi-stage method has a small number of admixture proteins. PMID- 2268711 TI - [Oligomerization of water soluble proteins of rabbit crystalline lens under the action of diamide]. AB - The study has examined the effects of the SH-oxidizing agent diamide (Diazane dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble portion of proteins from rabbit lenses. The dialyzed protein extracts were incubated for 1 1.5 hrs with various concentrations of diamide. Treatments were monitored for alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins. The response to 2 mM diamide treatment for 1 hr consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by an appearance of polypeptides with apparent molecular weights. The protein with molecular weight of 29 kilodaltons was shown to be involved in cross-linking. The linkages in the dialyzed water-soluble lens polypeptide fraction induced by diamide may be reduced by GSH (10 mM) treatment of protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that the described oxidative system of proteins may be a useful tool for cataract research. PMID- 2268710 TI - [Study of HDL2-dependent synthesis of bile acids in culture of rabbit hepatocytes: effects of oxidized cholesterol derivatives]. AB - The effect of individual oxysterols--products of auto-oxidation of cholesterol on bile acid synthesis by cultivated rabbit hepatocytes was studied. Relative rates of bile acid synthesis were measured as the conversion of 4-14C cholesterol-HDL2 into total 4-14C labeled bile acids. 7 beta-hydroxycholesterol and 3,5-cholestane 7-dione strongly inhibited bile acid synthesis at concentrations 1-10 micrograms/ml. These data support the hypothesis that oxidized cholesterol derivatives accelerate the development of hypercholesterolemia in rabbits fed on cholesterol containing diet. PMID- 2268712 TI - [Chromato-focussing of plasma low density proteins]. AB - A few alternatives of the binding of healthy patients plasma low density lipoproteins (LDL) with anion exchanger PBE-94 were revealed. In the first case the main part of LDL did not bind to the gel and the isoelectric points of the minor subfractions were 5.8 and 5.3, and pI 4.1. In the second case about half of lipoproteins did not bind to the gel, and the isoelectric points of subfractions were 5.7 and 5.0; and pI 4.1. In the third case when all lipoproteins bound to the PBE-94, there were much more subfractions and their isoelectric points were 6.2, 5.8, 5.2, 4.9, 4.5 and pI 4.1. All LDL of the patients with ischemic heart disease bound to anion exchanger, and the part of subfraction with pI 4.1 was three or five times as great as the one of the healthy person. Increasing of the LDL subfraction with pI 4.1 was observed at prolonged keeping of the LDL obtained from the healthy person plasma. LDL isoelectric point distribution of the persons with carcinoma uterine cervix did not differ from the one of the healthy persons. Acetylation and hexanol modification resulted in the isoelectric point shift from 5.7 to 4.6 and to 4.3 in the case of LDL subfraction to be obtained preparatively using the chromatofocusing. PMID- 2268713 TI - [Leukocyte filterability in whole blood]. AB - There was investigated the leukocyte and erythrocyte filtration in blood of 25 donors men. The blood filtration was performed through 5 m pores of nuclear filters at constant perfusion pressure 100 cm H2O. Erythrocytes didn't influence on the leukocyte filtration in blood. Filtration properties of leukocytes together with their number was more important at filtration of blood. PMID- 2268715 TI - [Effects of delta sleep-inducing peptide on electrophysiological parameters of sleep during alcohol withdrawal in rats]. AB - In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice. PMID- 2268714 TI - [Microdialysis study of release of adenine nucleotide breakdown products into the intercellular space of the myocardium in ischemia and reperfusion]. AB - Interstitial concentrations of adenine nucleotide breakdown products (ANBP)- adenosine (ADS), inosine (INS), hypoxanthine (HYP), in perfused rat hearts were measured during total ischemia and reperfusion by microdialysis technique. Progressive accumulation of ANBP in the interstitial space was observed during ischemia, but unlike INS and HYP, maximal ADS concentration was reached not by the end of ischemia but after the beginning of reperfusion. During reperfusion the qualitative accordance between changes in ANBP levels in the interstitial space and venous effluent was observed, but interstitial concentrations were several times greater. PMID- 2268716 TI - [Effects of inmecarb on alcohol intake and the state of hepatic cytochrome P-450 system during various stages of experimental alcoholism in rats]. AB - The influence of the new anti-alcohol drug Inmecarb on the alcohol consumption as well as on activity of the liver cytochrome P-450 system was studied in rats during chronic alcohol intoxication in the free choice situation between water and 15% ethanol solution. It was shown that voluntary alcohol consumption of different duration (10 days to 8 months) does not change the activity of liver cytochrome P-450 system. Inmecarb treatment (40 mg/kg, i.p. twice a day) during 14 days resulted in decrease of alcohol consumption in rats. This effect was most pronounced in late stages of experimental alcoholism. Inmecarb decreases the cytochrome P-450 content and suppresses the activity of aniline hydroxylase in rats with different duration of voluntary alcohol intoxication, but most pronounced effect was observed during the late stages of experimental alcoholism. PMID- 2268717 TI - [Formation of biologically active substances during cholesterol oxidation on the surface of fluorocarbon emulsions]. AB - Oxidative modification of cholesterol on the surface of fluorocarbon emulsions was studied. The oxidation yielded one primary product--7-peroxycholesterol. It was shown that the obtained cholesterol C7 derivatives possess a high biological activity. It was concluded that the possibility of oxidative modification of plasma substances on the surface of fluorocarbon emulsion particles with the formation of highly active compounds must be taken into account when using the fluorocarbon particles in medicine. PMID- 2268718 TI - [Monoclonal antibodies to individual antigens of the nervous system of the snail, Helix pomatia]. AB - Seven positive hybridoma clones were chosen by immunoenzyme analysis amons 103 clones obtained by hybridization of NSO plasmocytoma cells and splenocytes from BALB/C mice, immunized with snail's nervous system antigens. Specific binding of Mabs with neuron cytoplasmic antigens was indicated on cryostat sections of visceral, pedal and cerebral ganglia. The Mabs obtained could be used for the study of physiological role of antigens identified. PMID- 2268719 TI - [Enzyme indicator of the immunobiologic activity of antigens]. AB - The test-system has been elaborated for the determination of the ability of different antigens in the cultures of the mouse peritoneal macrophages. Measuring an intracellular acid phosphatase activity, reflecting the extent of the cell activation, was taken as a principle of this test-system. With the help of this test-system ability of a few antigens (lipopolysaccharide, polysaccharide, glycoprotein, protein and low molecular weight substances--peptide and glycopeptide) have been studied. It is testified that above mentioned antigens possessed different effects on the acid phosphatase activity. PMID- 2268720 TI - [Immune response to a synthetic polysaccharide and protein conjugate]. AB - Synthetic polysaccharide (S-PS) containing aglycone-spacer with a free amino group was really alpha 1,6-mannan with Cn approximately 10. S-PS was transformed into isothiocyanate derivative by treating it with thiophosgene and engaged into reaction with amino group of bovine serum albumin (BSA) lysine residues. Rabbits were immunized with S-PS-BSA conjugate and antibodies to S-PS titres were estimated by means of ELISA. S-PS-BSA conjugate was proved to provoke specific anti-polysaccharide antibodies formation in rabbits. PMID- 2268721 TI - [Caused of intensified lipid peroxidation in the blood of patients with viral hepatitis B]. AB - The tissue oxygen concentration, the serum antioxidant system state and the serum malondialdehyde (MDA) concentration were studied in patients with hepatitis B. The good correlations were studied in patients with hepatitis B. The good correlations between MDA concentration in patients serum and the oxygen concentration in tissues (R-0.79), and the cytoplasmic enzymes activity (R-0.75 for lactate dehydrogenase; R-0.75 for alanine transferase) were found. On the other hand, it was shown an antioxidant activity decrease of ceruloplasmin transferrin system in patients serum. It is proposed, that the tissue hypoxia and the decrease of the serum antioxidant activity are the general factors leading to the MDA accumulation in the serum of patients with hepatitis B. PMID- 2268722 TI - [Role of cathepsin D in the appearance of micronuclei in lung cells of mice immunized with influenza vaccine]. AB - The positive correlation of micronuclei quantity appearance and catepsin D activation in mice cells after immunization by alive influenza vaccine was demonstrated. Activation of proteinase precedes chromosomal aberrations. Catepsin D activation is supposed to lead to proteolysis in achromatic apparatus which results in micronuclei formation. PMID- 2268723 TI - [Systems of surface exclusion of F-like plasmids of E. coli and their genetic control]. AB - The F-like plasmids belonging to 5 different Sfx-groups were discovered. The existence of atypical plasmids belonging to different Sfx-groups was shown. The molecular cloning of plasmid DNA fragment (3.9 mD) determining SfxII phenotype was performed. PMID- 2268724 TI - [ Anticataleptic effect of delta sleep-inducing peptide and its action on brain monoamine oxidase in rats genetically predisposed to catalepsy]. AB - Rats with genetic susceptibility to catalepsy (GC strain) were compared with Wistar rats (W). After an intraperitoneal administration of 120 micrograms/100 g delta sleep-inducing peptide (DSIP) in GC rats the duration of cataleptic freezing was shortened (13.8 +/- 9.5 sec against 27.2 +/- 7.5 sec in control). MAO-B activity decreased due to DSIP administration both in GC and W rats. It is hypothesized that the DSIP effect MAO-B in GC rats may correct the lost MAO-A function in deamination of dopamine, a common MAO-A and MAO-B substrate, and the dopaminergic neurotransmission in catalepsy. PMID- 2268725 TI - [Sensitivity of tumor cells to cytostatic action of NK cells and their capacity of releasing prostaglandin E]. AB - The studies of twelve tumor cell strains revealed the correlation between the degree of their malignancy and their capacity to secrete PGE following in vitro contact with NK cells. Actively secreting PGE tumor cells were shown to be highly resistant to CTA of NK cells. Apparently, the ability of tumor cells to secrete PGE following the contact with NK cells and inhibition of their CTA are one of the mechanisms of tumor cell defence against NK cytotoxicity. PMID- 2268727 TI - [Effects of autotransplantation of minced muscle tissue and subsequent laser therapy on recovery of the muscle injured by irradiation]. AB - A comparative histological investigation of posttraumatic regeneration in irradiated with 30 or 40 Gy and cross-sectioned musculus gastrocnemius of rats after autotransplantation into muscle defect of non-irradiated minced muscle tissue and laser therapy of hind limb in post-operative period was conducted. The obtained results showed that in irradiated with 30 Gy sectioned muscle (control series) the inflammatory reaction, resorption of fibrin in the area of trauma were inhibited and proliferation of muscle tissue from proximal and distal stump was suppressed. The rough connective tissue scar was formed. In experimental series for stimulation of regeneration the method of autografting minced muscle tissue into the defect of irradiated (30 or 40 Gy) cross-sectioned muscle and combination of this method with helium-neon laser rays exposition was used. The more marked recovery was obtained in irradiated with 30 Gy operated muscle after a 10-day treatment of limb with laser rays. PMID- 2268726 TI - [Comparative accumulation of the Hoechst 33258 fluorescent probe in leukemia P388 cells sensitive and resistant to doxorubicin]. AB - The authors studied accumulation of the fluorescent probe Hoechst 33258 in leukemia P 388 sensitive (P 388/0) and resistant to doxorubicin (P 388/DOX) cells. It was shown that intensity of fluorescence of the dye increased after binding with nuclear DNA during 25 min for both lines of the cells. Intensity of fluorescence was 40% greater in sensitive than resistant cells. If Triton X-100 was added no difference between two lines of the cell was observed. When doxorubicin was added to the cells with dye, the intensity of fluorescence decreased. It was suggested to use Hoechst 33258 for assessment extent doxorubicin accumulation in nuclei of the cells. PMID- 2268728 TI - [Study of changes in the amplitude of circadian rhythms in postnatal development]. PMID- 2268729 TI - [Features of energy metabolism of myocardial mitochondria and their ultrastructure in normal and immobilized rats of different animal social rank]. AB - The oxidative and phosphorylating functions of mitochondria (M) and their ultrastructure were studied in the myocardium of normal and 6.5-hour immobilized rats that belonged to different zoosocial groups. M from dominant rats under normal conditions were shown to exhibit higher energy and to possess better respiratory energy regulation than those of "outcast" rats. However, the ultrastructure of M had no group specificity in normal. The immobilization caused more profound changes in M from the dominant rats and led to a more pronounced swelling of M in the myocardium of the above rats than in the "outcast". M from the subdominant rats were most resistant to an immobilization stress. PMID- 2268730 TI - [Effects of bronchial secretions of patients with bronchial asthma and chronic bronchitis on the motility of ciliated cells of the ciliated epithelium]. AB - It has been shown that bronchial mucus from patients with bronchial asthma and chronic bronchitis can produce a ciliostatic effect when incubated with strips of frog palate mucosa. This effect can more often be found during clinical exacerbation and is supposed to be reversible. The ciliostatically active samples of bronchial mucus taken from asthmatic patients markedly inhibit reactivation glycerol models of frog's ciliated epithelium. It can therefore be suggested that the found activity acts directly on tubulin-dynein complex of the cilia. In contrast to these findings, the ciliostatically active samples of bronchial of glycerol models and therefore possibly act through some other mechanism. PMID- 2268731 TI - [Characteristics of the course of regeneration process in the muscles of replanted rat extremities]. AB - The analysis of the changes in the muscles of replanted terminals in early and late stages was made by the method of electron microscopy. In early stages neurogenic atrophy was observed which progressed due to the destructive regenerative process caused by incomplete innervation, deepening microcirculatory disorders and, likely, autoimmune reactions. PMID- 2268732 TI - [Contractile activity of lymphatic microvessels in fever reaction]. AB - Contractile activity of the wall and lymphatic microvessels (LM) valves of small intestine mesenterium in experimental fever reaction (FR) under vital microscopy conditions has been studied in the experiments on rats. FR was accompanied by considerable quantitative (the increase of the number of contractile LM and their valves, the rising of their contractile activity) and qualitative changes of LM contractile activity. The increase of spontaneous vasomotions frequency and closing of valves cusps was observed. Contractile apparatus of the wall and LM valves becomes more active in FR due to biogenic amines mobilization from perivascular sympathetic terminals and mast cells. PMID- 2268733 TI - [Some characteristics of the histological structure of the fetal bovine pancreas]. AB - Some properties of histological structure of fetal bovine pancreas were demonstrated using light microscopic methods. The different forms of acino insular complexes were described: 1) acino-insular complexes with single B-cells including epithelial layer of acini; 2) acino-insular complexes with segmental (sector) localization of insular cell groups; 3) acino-insular complexes with small and more large groups of endocrine cells timely contacted with acini; 4) acino-insular complexes at the stage of separation of endocrine cell groups (microislets) from acini. The consideration of acino-insular complexes in morphogenesis of bovine endocrine pancreas in discussed. PMID- 2268734 TI - International Standards for salmon calcitonin, eel calcitonin, and the Asu1-7 analogue of eel calcitonin: calibration by international collaborative study. AB - Regulatory specifications in most countries require that the potency of salmon calcitonin (sCT) clinical products be expressed in International Units (IU) defined by the World Health Organization (WHO) International Standard. The first ampouled standard was prepared in 1972 and has been distributed world-wide since then. A batch of ampoules to serve as the replacement standard is now required. Other piscine calcitonins, eel calcitonin (eCT) and an amino-suberic acid analogue of eCT (Asu1-7 eCT) are now clinical products in some countries and international standards are required for these peptides which are similar to, but not identical with, sCT. This paper describes the preparation of three new ampouled standards and their biological calibration by international collaborative study comprising 17 participants from 10 countries. Following the recommendations in the final report of the collaborative study, the 2nd International Standard (IS) for sCT, the 1st IS for eCT and the 1st IS for Asu1-7 eCT were recently established by WHO, each with an assigned potency in IU, and are now available for issue. PMID- 2268735 TI - Bone mass and anthropometric measurements in adult females. AB - Bone mass and anthropometrics were measured in 342 adult female twins, aged 25-79 (mean = 44.1 years) for the purpose of: (1) identifying which anthropometric measurements were most strongly associated with bone mass at various skeletal sites, and (2) determining the accuracy of combinations of these measurements in the prediction of bone mass. Among the eight skinfolds measured, the subscapular site was more strongly correlated with all bone mass measurements than any other skinfold. Similarly, calf circumference (among four sites) and biacromial width (among five frame size measurements) provided the strongest correlations within these groups of anthropometrics with all bone sites. The somewhat surprising consistency of these results was then tested in multivariable models for the prediction of bone mass. For the entire study group, each of the anthropometric measurements (subscapular skinfold, calf circumference and biacromial width) were independent, significant predictors of bone mass, even when height, weight and age were included in the models. These data suggest that frame size, muscularity and adiposity have independent effects on the skeleton, and that single measurements of each of these anthropometric characteristics are associated with all skeletal sites. PMID- 2268736 TI - Biomechanical effects of the full range of useful doses of (3-amino-1 hydroxypropylidene)-1,1-bisphosphonate (APD) on femur diaphyses and cortical bone tissue in rats. AB - The effects of i.p. doses of 0.016, 0.16, 1.6, 5, 16, 50 and 160 microM/kg/day of APD, over a period of 23 days, on geometric and biomechanical properties of femoral diaphyses in bending were determined in groups of seven growing rats. Both elastic and ultimate strength increased with low doses and decreased with high doses. Geometric (mass) variables (diaphyseal volume, wall/lumen ratio) correlated positively, and material properties (limit elastic stress, modulus of elasticity) negatively, with log dose. Normal mass and improved quality at low doses, and improved mass and impaired quality data at high doses were obtained. No changes in sectional moment of inertia (Ix, an expression of bone architecture) were observed. Biphasic changes in diaphyseal strength expressed the effects of APD on material quality in spite of mass variation. The contrasting lack of changes in Ix may have reflected the blocking effect of APD on osteoclast-osteoblast communication, essential for directional modulation of remodelling. PMID- 2268737 TI - Acute effect of prolactin on the intestinal calcium absorption in normal, pregnant and lactating rats. AB - Acute effect of prolactin on intestinal calcium absorption was studied in Wistar rats. Prolactin when given subcutaneously 24 h, or intraperitoneally 1 h, before intragastric administration of 45Ca-containing CaCl2 solution markedly increased the plasma 45Ca content. Of interest was the enhancing effect of prolactin on calcium transport seen in 1 h which suggested that prolactin could act directly on the intestine. Physiological significance of prolactin was evaluated in pregnant and lactating rats. Pretreatment with bromocriptine, an inhibitor of prolactin release, had no effect in rats on day 20 of pregnancy but significantly reduced calcium absorption in lactating rats. This reduced calcium absorption was only partially restored by prolactin treatment. The present investigation thus showed that prolactin, besides stimulating 1,25(OH2)D3 production, may also enhance calcium absorption directly. This effect was absent in pregnant rats but was of physiological significance in lactating rats. PMID- 2268738 TI - The ovariectomized, lactating rat as an experimental model for osteopenia: calcium metabolism and bone changes. AB - The ovariectomized, lactating rat (Sprague-Dawley) is proposed as an experimental model for the rapid development of osteopenia which may be used to test the effectiveness of bone-retentive drugs potentially useful in treating osteoporotic women. Rats were ovariectomized (OVX) on day 2 postpartum and were kept on a low calcium diet (0.1%). Measurements of serum total calcium, ionic calcium, albumin and parathyroid hormone were conducted between days 4 and 21 of lactation. Serum total and ionic calcium and albumin were significantly lower and serum parathyroid hormone was significantly higher in all lactating rats at 16 days postpartum compared to nonlactating controls. Mean bone mass of the femurs of OVX lactating rats measured at day 21 was approximately 50% of that of non-lactating intact controls. The enhanced duodenal calcium absorption (in everted gut sacs) associated with lactation was not affected by OVX and neither was the average litter weight gain between 2 and 14 days of lactation. In conclusion, lactation coupled with a low-calcium diet resulted in marked osteopenia, depressed serum calcium (both total and ionic) and significantly elevated serum parathyroid hormone concentration. The rapid and extensive bone loss of this model makes it appropriate for the study of therapeutic agents designed to retain bone mass. PMID- 2268739 TI - Estrogen-calcium interactions in the postmenopause: a quantitative description. AB - Accumulated data describing the time course of bone loss in postmenopausal women were combined with metabolic data on estrogen-calcium interactions to produce a comprehensive, quantitative model of involutional bone loss. The model was shown to be able to mimic results of published intervention studies with considerable fidelity. Implicit in existing understanding, and made explicit by the model, are such relationships as: (1) calcium deficiency, if present in a woman, is masked during the early years of estrogen withdrawal bone loss; (2) accordingly, except in severe deficiency states, it is unlikely that calcium supplementation can confer much benefit in the immediate postmenopause; (3) however, by 5-8 years postmenopause, an underlying calcium deficiency, if present, becomes manifest, and if uncorrected will greatly augment the bone loss produced by estrogen withdrawal; (4) estrogen replacement therapy, if stopped, does not produce a sustained difference in bone mass in calcium-replete women; however, (5) estrogen, by effectively reducing the level of any calcium deficiency that may be present, does produce a permanent benefit in women with such deficiency. These relationships suggest that late fracture protection from earlier estrogen therapy is either confined to women with calcium deficiency, or has a non-mass basis (or both). PMID- 2268740 TI - Increase of bone mineral density by calcium supplement with oyster shell electrolysate. AB - The effect of calcium supplementation, in patients with osteoporosis is still a matter of controversy. Oyster shell electrolysate (OSE) was reported to raise serum calcium and increase urinary calcium excretion in vitamin D-deficient states more readily than calcium carbonate. Since the effect of calcium salts on osteoporosis depends heavily on its bioavailability, the effect of 900 mg/day calcium as OSE was tested in 12 elderly osteoporotic females, using radial bone mineral density measured by single photon absorptiometry and spinal trabecular bone density measured by quantitative computed tomography (QCT) as indicated, in comparison with 21 untreated controls in the same geriatric hospital. Radial bone mineral density significantly increased from the pre-test value after 12 and 24 months in subjects given OSE by paired t-test, whereas it fell significantly in the controls. The spinal QCT value on OSE did not change significantly in either the subjects under treatment with OSE, or the controls. Thus OSE may favorably influence osteoporosis by providing a readily available source of calcium. PMID- 2268741 TI - High indices of remodelling in iliac trabecular bone predict reduced forearm cortical bone mass indices in patients with proximal femoral fractures. AB - To investigate whether high bone turnover could be a predictor of cortical bone loss and a candidate risk factor for fractures of the proximal femur, 33 7.5-mm transiliac biopsies taken at fracture fixation from 48 patients who participated in a study of potential risk factors have been quantitated. Twenty-four of the 33 patients made good recoveries and about 6 weeks postoperatively consented to bone densitometry of the forearm midshaft. Forearm bone density correlated negatively (r = 0.77, P = 0.001) with the surface of trabecular bone covered with osteoid, which in osteoporotic patients with crush fractures of the vertebrae was previously shown to relate both to rates of bone formation and resorption. An important minority of these femoral fracture patients appeared to be suffering from high rates of iliac trabecular bone resorption. Thus, high bone remodelling activity could lead to excessive cortical thinning. This has pathogenetic implications which may be clinically important. PMID- 2268742 TI - An in vivo model system for the study of avian osteoclast recruitment and activity. AB - We have developed a model system for the study of osteoclast recruitment and activity using devitalized bovine cortical bone slices implanted onto the chorioallantoic membrane (CAM) of chicken embryos. Bone slices were examined after 3, 6, and 8 days of incubation on the CAM. A marked cellular reaction to the bone was observed, characterized by a prominent angiogenic response. Upon histological examination, numerous multinucleated giant cells were associated with the undersurface of the bone slice and concentrated towards its periphery. These multinucleated cells were often associated with resorption lacunae and demonstrated ruffled borders when viewed by transmission electron microscopy. Removal of the cells and examination of the bone surface by scanning electron microscopy revealed numerous resorption pits characteristic of osteoclastic activity. These pits were evident on day 3 of incubation and appeared to be more extensive by day 8. This work demonstrates that the cells recruited to such ectopically implanted devitalized bone slices are functional osteoclasts, and that this system may provide a useful model for the study of osteoclast recruitment and activity. PMID- 2268743 TI - Osteochondral differentiation and the emergence of stage-specific osteogenic cell surface molecules by bone marrow cells in diffusion chambers. AB - The osteochondral potential and emergence of osteogenic cell-surface molecules by avian marrow cells was evaluated in in vivo diffusion chamber cultures. The chambers were inoculated with unselected marrow cells from young chick tibiae and implanted intraperitoneally into athymic mice. At the light microscopic level, morphologic evidence of de novo bone and cartilage formation, including specific immunostaining by antibody probes, was observed in 14 out of 16 chambers incubated for 20 days or longer. In order to monitor the osteogenic differentiation of the marrow-derived cells, indirect immunofluorescence was performed with monoclonal antibodies against stage-specific cell surface antigens on cells of the embryonic osteogenic lineage. The binding of these and other specific monoclonal antibodies in the developing tissue indicates that the cell surface and extracellular matrix molecules expressed by descendants of marrow derived mesenchymal progenitor cells are indistinguishable from their in vivo counterparts found in embryonic skeletal structures. Furthermore, the experiments reported here describe the first molecular identification of osteogenic cells by probes which are selective for stage-specific surface antigens on cells of the osteogenic lineage. Importantly, bone formation by these marrow-derived cells appears to occur through a lineage progression which is similar to that observed for embryonic tibial osteoblasts. In summary, these data support the use of diffusion chambers inoculated with avian marrow to study aspects of osteogenic and chondrogenic differentiation. PMID- 2268744 TI - Effects of fluoride on rat cancellous bone. AB - Female Wistar rats were divided into four groups each fed ad libitum regular rodent chow and fluoridated water at four levels (0, 2, 4, 6 mmol/l) for 3 months. There were significant differences in ash weights between control and fluoridated vertebrae (P less than 0.01). Intact bone fluoride (F) values observed were: 0.04 +/- 0.01% fat-free dry weight (ffdw) for control vertebrae and 0.22-0.34 +/- 0.03% ffdw for fluoridated vertebrae. Deproteinized fluoridated vertebral bone had significantly lower specific surface area (SSA) (from 100 +/- 19 m2/g, P less than 0.01, down to 80 +/- 20 m2/g, P less than 0.001) than the control group (120 +/- 10 m2/g); a finding in support of our hypothesis that more of the bone mineral units in fluoridated bone are older (hence denser) than in normal bone. Static morphometric analysis of toluidine blue-stained sections of the femoral metaphyses showed that both cancellous bone volume/tissue volume (Cn BV/TV) and trabecular thickness (Tb.Th) increased linearly with NaF dosage (R = 0.99 and 0.97, respectively); with Cn-BV/TV increasing from 21 +/- 7 to 33 +/- 6% (P less than 0.01) and Tb.Th from 76 +/- 8 to 98 +/- 9 microns (P less than 0.01). Similar Cn-BV/TV results were also obtained from von Kossa-stained sections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268745 TI - Technical variability of bone histomorphometric measurements. AB - Effects of main sources of bone biopsy sample variability have been examined. Variability was assessed in double iliac crest biopsies of 12 subjects with normal or pathological bone. Components of variance were estimated as follows: two biopsies per patient; three specimens at different distances from compact bone; three sections per specimen; three microscopic fields per section. The following indicators were measured: bone volume (BV/TV); osteoid volume (OV/BV); osteoid surface (OS/BS); osteoblast surface (Ob.S/BS); eroded surface (ES/BS); osteoclast surface (Oc.S/BS); osteoid thickness (O.Th). Sources of variability were assessed by ANOVA for random effects. On the basis of the results, between fields variation gave the main contribution to the error of single measures (BV/TV, 50%; O.Th, 70%; OV/BV, Ob.S/BS, OS/BS, Oc.S/BS, ES/BS more than 80%). Distance from compact bone affected mostly the BV/TV (40%) and the O.Th (10%) error. When bone specimens at intermediate distance from cortical bone are examined, variations due to different biopsies, different section and different microscopic field are largely reduced by measuring 12 microscopic fields for BV/TV (14%) and 48 microscopic fields for the other indicators (O.Th 16%; OV/BV, Ob.S/BS, OS/BS, Oc.S/BS, ES/BS more than 30%). The precision can be only slightly improved by further increasing the number of the microscopic fields. PMID- 2268746 TI - Bone histomorphometric reference values in 88 normal Italian subjects. AB - The study deals with bone histomorphometric results obtained from 88 normal subjects (38 women and 50 men; range: 20-89 years), in order to establish control values in an Italian population. Bone specimens were obtained at autopsy from a standardized area of the iliac crest. The following indicators were measured: bone volume (BV/TV), osteoid volume, osteoid surface, osteoblast surface, eroded surface, osteoclast surface, osteoid thickness. Dependence of histomorphometric indicators on sex and age was evaluated by multiple regression analysis, including sex, age, and also a quadratic term (age2) and two interaction terms (sex x age, sex x age2). BV/TV was mainly affected by age. In fact, a decrease in the amount of bone was found with increasing age in both males and females. The reduction appeared rather regular, with negligible differences between males and females. The other indicators were found to be age- and sex-independent. As a consequence, they did not give information on the possible changes of bone apposition and resorption processes due to aging. On the whole, histomorphometric indicators of trabecular bone of the normal Italian population do not greatly differ from those reported for most other caucasian people. PMID- 2268747 TI - Partial gastrectomy and mineral metabolism: effects on gastrin-calcitonin release. AB - Bone mineral metabolism was studied in 20 male patients, between 8 and 18 years, after surgical treatment for peptic ulcer (ten Billroth 1 and ten Billroth 2 gastrectomies) and in 16 sex- and aged-matched healthy controls. The bone mineral content was statistically reduced only in the Billroth 2 group. Serum 25(OH)D was lower in all patients, but fractional calcium absorption was similar to the control value. This may be due to increases in 1,25(OH)2D and parathyroid activity (particularly in Billroth 2). Serum osteocalcin levels and hydroxyproline excretion were higher than in the controls. A positive linear correlation emerged not only between serum 1,25(OH)2D and PTH levels but also between each of these and serum osteocalcin and urine hydroxyproline. Both PTH and calcitriol were inversely correlated with the bone mineral mass in Billroth 2, confirming a trend observed in Billroth 1. Although calcitonin values were normal, basal gastrin levels were severely impaired in all patients. In response to a mixed meal, increases in gastrin and calcitonin were significantly lower than in the controls. The calcitonin response to intravenous calcium and pentagastrin infusion was not significantly different to the controls. The percentage increase in gastrin and calcitonin responses to oral calcium correlated positively with the reduction in bone mineral content only in the Billroth 2 group, suggesting a reduction in calcitonin release may contribute to gastric surgery osteopenia in these patients. PMID- 2268748 TI - Dogs, distemper and osteitis deformans: a further epidemiological study. AB - There is extensive evidence linking paramyxoviruses, notably measles and respiratory syncytial virus, with Paget's disease of bone. The epidemiology of Paget's disease does not fit with that of known human paramyxovirus infections and it is possible that the disease is a zoonosis with domestic animals acting as host. Canine distemper, a paramyxovirus of the morbillovirus family (closely related to measles) is therefore a potential candidate. We have surveyed previous pet ownership in 150 Paget's patients each of whom was matched with two general practice controls; one from an inner city practice and the other from a suburban practice both in Greater Manchester. Recall of previous dog ownership was higher in Paget's patients with differences being more marked against inner city than suburban controls. 88% of the patients had lived in the same household as a dog at some stage compared with 79% of the inner city controls (P less than 0.05) and 83% of the suburban controls (n.s.). The differences were greater in the years 1930-60 during which the proportion of patients owning dogs was largest. For Paget's patients and controls alike, recalled exposure to dogs with canine distemper appeared to cluster in certain periods between 1930 and 1960. Unexpectedly, significantly more (7 out of 22, P less than 0.01) of the patients with a known first degree relative suffering from Paget's disease had no previous history of dog ownership when compared with the other patients (10 out of 128). PMID- 2268749 TI - A comparison of iliac bone histomorphometric data in post-menopausal osteoporotic and normal subjects. AB - Transilial bone biopsies following in vivo fluorochrome labeling were obtained from 90 women with postmenopausal osteoporosis and 34 healthy post-menopausal women. Standard histomorphometric data were collected from undecalcified sections. The distribution of values for both structural and remodelling indices was the same for each group. Bone volume was 35% lower (P less than 0.001), wall thickness was 12% lower (P less than 0.001), and trabecular thickness was 11% lower (P less than 0.02) in osteoporotics. Trabecular separation was 34% greater (P less than 0.001) and trabecular number was 36% lower (P less than 0.001) in osteoporotics. Biopsy core width was 11% less (P less than 0.02) and cortical width was 35-50% less (P less than 0.001) in osteoporotics. Static indices of remodelling, mineralizing surfaces, and mineral apposition rate were similar in the two groups. The absolute values for bone histomorphometric variables for both groups are similar to most published data. Osteoporotics had poorer bone structure, marked by decreased trabecular connectivity and thin cortices. There were no major differences in dynamic indices of remodelling. Since the histomorphometric data were distributed the same in both groups, special subsets of osteoporotic subjects not in the normal population did not exist. PMID- 2268750 TI - Osteomalacia and osteoporosis in femoral neck fracture. AB - Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification. PMID- 2268751 TI - In memoriam Karl Augustus Menninger, MD (July 22, 1893-July 18, 1990). PMID- 2268752 TI - The Exploitation Index: an early warning indicator of boundary violations in psychotherapy. AB - Exploitive behavior by therapists is highly disruptive in psychotherapy because it violates the sense of trust derived from a coherent treatment boundary. Such behavior may be difficult to detect because it is often associated with self deception. The compensatory need to feel "special," a state of mind often associated with exploitiveness, suggests that narcissistic mechanisms play a significant role. The authors present an "Exploitation Index" (EI), a self assessment questionnaire for therapists that is designed to serve as an early warning indicator of boundary violations. PMID- 2268753 TI - Exploration of nightmares in hospital treatment of borderline patients. AB - A clinical investigation of nightmares enhanced the psychotherapy of many hospitalized borderline patients. Early familial trauma, prominent in the latent content of the nightmares, predisposed these patients to adult dysfunction or to a maladaptive response to subsequent trauma. The hospital ward's emphasis on intergenerational family therapy and the well-integrated holding environment helped offset distress in patients resulting from the upsurgence of conflictual material latent in their nightmares, whether or not they were posttraumatic. The authors present illustrative cases. PMID- 2268754 TI - Therapist envy. AB - The vicissitudes of envy comprise some of the most powerful relationships between people. Originally viewed as a character trait, envy is now viewed as occurring in two-person interpersonal interactions. The therapeutic situation is therefore an ideal context in which to examine envy on the part of both therapist and patient. Envy is an intense affect, inhibiting effective behavior, and it may damage the therapeutic relationship in ways not easily recognized by therapist and patient. PMID- 2268756 TI - Obsessional thinking as "paradoxical action". AB - Obsessive-compulsive neurosis has long intrigued psychoanalysts. Although they may disagree about the underlying etiological mechanisms, analysts generally agree that obsessive individuals are often difficult to engage in the psychoanalytic process and are therefore difficult to treat psychoanalytically. The author offers a selective integration of theoretical approaches to this disorder and elaborates on Schafer's theory of obsessional thinking as paradoxical or conflictual action as a way to understand the resistance frequently encountered in these patients. A case report illustrates this psychoanalytic approach to obsessional neurosis. PMID- 2268755 TI - Classical psychoanalysis and object relations theory in the analysis of character. AB - The analysis of character begins with repeated interpretation of its defensive structure and later moves into the analysis of object relations. What appears at first to be a patient's defenses against instinctual impulses may subsequently be recognized as defenses against emotional reactions to early objects. Nevertheless, at the beginning, interpretations should be directed toward the clinical material already available, and not at what may eventually emerge according to the analyst's theory. The author presents a case report to illustrate this viewpoint. PMID- 2268757 TI - Adolescent anger. AB - Adolescent hostility, resentment, blame, and reproach are dynamically determined and serve important defensive, alloplastic, and restitutional aims. The author examines how these negative affects, the accompanying victim role, and oppositional defiance enable angry adolescents to defend against depression and loss, to demand nurturance from others, to protect their precarious inner autonomy, and to undo their humiliation and shame by vengeance and reversal. The author suggests that adolescent anger arises from an underlying wish to coerce objects into providing all-giving restitution for losses and narcissistic injuries, not necessarily from a wish to sadistically or enviously destroy them. PMID- 2268758 TI - Summoning a punishing angel: treatment of a depressed patient with dissociative features. AB - The authors describe their treatment of a 24-year-old repentant, extremely observant Jewish man with major depressive disorder who complained of persecution by a personal angel. The therapists initiated a culturally sensitive psychotherapy of the patient, enacting a ritual summoning of the angel that resulted in the angel's transformation into an ally. The authors discuss the relationship of the patient's symptomatology to pathological mourning, trance, and dissociation. They advocate the use of a strategic combination of culture specific concepts with modern psychiatric approaches in similar cases. PMID- 2268759 TI - The endocrine system and connective tissue disorders. AB - The face of many endocrine diseases is rapidly changing as early detection and intervention is achieved. Nevertheless, certain musculoskeletal symptoms can suggest a possible endocrinopathy. The clinician can expect the appearance of particular rheumatic problems during the course of a chronic endocrine disorder. This is especially germaine for diabetes and acromegaly, in which the disorder is controlled but not cured. Clearly hormones play a critical role in the development and expression of immunologic disease. Sex hormones and calcitriol have a direct effect on basic immunobiology (3). The rheumatoid synovium responds to parathyroid hormone and calcitriol in concert with local signals such as prostaglandins, interleukins, and interferon (2,77). Finally, the immune system plays a central role in the pathogenesis of several endocrine diseases. The thyroid diseases, Graves' disease and Hashimoto's disease are best studied. The mechanisms of Ia expression leading to immune destruction and lymphocytic infiltration of the gland will be applied to other endocrine disorders. PMID- 2268760 TI - Gallbladder wall thickening (congestive cholecystopathy) in chronic liver disease: a sign of portal hypertension. AB - A thickened gallbladder wall is often seen with ultrasound in alcoholic cirrhosis. Hypoalbuminaemia is thought to be the cause since there is a strong association between bowel wall thickening and low serum albumin. To determine the role of portal hypertension in producing gallbladder wall thickening we studied 40 consecutive stable patients-37 with cirrhosis and three with portal hypertension due to primary biliary cirrhosis. Ultrasound assessment of the gallbladder wall was made after an overnight fast using a Technicare autosector. Wall thickness 4 mm or greater was considered abnormal. Twenty-seven patients had a thickened gallbladder wall and all had evidence of portal hypertension. Hypoalbuminaemia was not an important factor since it was only present in six cases with thickened walls. In two cases reduction in portal pressure with oral propranolol was associated with a decrease in gallbladder wall thickness. These results suggest that portal hypertension, not hypoalbuminaemia, is the dominant factor causing gallbladder wall thickening in cirrhosis. Ultrasound demonstration of gallbladder wall thickening in chronic liver disease should suggest the presence of portal hypertension. PMID- 2268761 TI - Computed tomographic assessment of old calcaneal fractures. AB - Prolonged pain and disability are common complications of calcaneal fractures. A prospective study was conducted on the value of computed tomography (CT) in 63 patients with 73 calcaneal fractures sustained more than 6 months before. The fractures were classified from the initial plain radiographs, and the patients' current clinical condition assessed in terms of a "disability score". The mean disability scores (MDS) associated with the different types of fracture were correlated with the CT findings. The highest MDS was found in the intra-articular fracture group which comprised 71% of the series. In this group the MDS was increased in the presence of post-traumatic osteoarthrosis of the subtalar joint (61% of cases), involvement of the calcaneocuboid joint (39% of cases) and subluxation/dislocation of the peroneal tendons (47% of cases). Structural abnormalities of the peroneal tendons were associated with a higher MDS including chronic tenosynovitis (eight cases), chronic partial tendon rupture (eight cases), complete peroneus brevis tendon rupture (two cases) and scarring indicating stenosing tenosynovitis (14 cases). A similar spectrum of appearances affecting the medial tendons of the hindfoot was identified in eight cases. Direct CT measurements of the degree of comminution did not correlate well with the patients' MDS. In the patient with persistent symptoms, CT is of value in the later assessment of long-term complications by revealing abnormalities of the subtalar joints and adjacent tendons. PMID- 2268762 TI - Real-time digital contrast enhancement and magnification in the assessment of scaphoid and other wrist injuries. AB - A study on the value of a commercially available desk-top digital magnifier contrast enhancer (DETECT System) was made in a series of 550 patients presenting with an acute wrist injury. Four radiologists, of varying experience, independently reviewed the radiographs on a conventional lightbox and later with the digitizer. In the scaphoid series (350 cases), the performance of the two more experienced radiologists was marginally better with the digitizer, whereas the less experienced radiologists performed slightly worse. Overall the digitizer improved the confidence of the radiologists in diagnosing correctly the presence of a scaphoid fracture but, for the less experienced radiologists, this was at the expense of identifying normality. In the wrist series (200 cases), the use of the digitizer resulted in a minor increase in the true positive and decrease in the false negative observations, but this was offset by a concomitant minor increase in the false positive and decrease in the true negative categories. Evaluation of the soft-tissue planes around the wrist joint showed a limited value in the identification of a scaphoid fracture with an overall positive predictive value of 0.26. Correlation of soft-tissue changes and the presence or absence of a scaphoid fracture was slightly worse with the digitizer. Possible causes for the apparently poorer performance of the digitizer are discussed, as well as the relative merits and potential value of the unit. PMID- 2268763 TI - The prognostic significance of radiologically detected knee joint effusions in the absence of associated fracture. AB - The significance of radiologically detected knee joint effusion as a marker of soft tissue injury following trauma is uncertain. In this study 100 patients presenting to the casualty department following acute injury, with effusions but no fracture, were assessed. Of those available for follow-up, 20% required further investigation and 11% proceeded to surgery for significant soft tissue injury. It is concluded that radiologically detected knee joint effusions are a useful marker for underlying soft tissue injury. PMID- 2268764 TI - Magnetic resonance imaging of primary skeletal muscle diseases: patterns of distribution and severity of involvement. AB - Magnetic resonance imaging of the lower extremities was performed with a low field system in 51 patients representing three different categories of biopsy proven primary skeletal muscle disease; muscular dystrophies, congenital myopathies and polymyositis. The intermuscular distribution of abnormal signal intensity and the grade of involvement of individual muscles were assessed. Large differences in the degree of pathological signal intensity between individual muscles were found in all categories. In the muscular dystrophy and polymyositis patients, the overall involvement was significantly more severe than in patients with congenital myopathy. Definite patterns of selective involvement were seen. Statistical evidence of selective muscle sparing was found; the gracilis muscle was significantly less affected than the other muscles in all three disease groups. Other muscles with significant sparing include the rectus femoris and sartorius muscles of the thigh and the tibialis posterior muscle of the leg. Common anatomical and functional characteristics of muscles may be related to the distribution of muscular disease. PMID- 2268765 TI - The influence of a seventy-two hour gap on the acute response of mouse skin and oesophagus. AB - The sparing effect of a 72 h gap, inserted after the third, sixth or ninth fraction of a 12 fraction X-ray schedule, was investigated in two early responding normal tissues: mouse skin and oesophagus. Acute skin reactions and body weight loss were used as assays to quantify changes in the radiation tolerance of these tissues. In skin, no evidence of compensatory proliferation was seen if a gap was inserted, whatever its position in the schedule. In oesophagus, a small but significant increase in radioresistance was observed if the gap was positioned 1/4 of the way through treatment compared with the schedule delivered without an interruption (12F/12 days). Although an increase in normal tissue tolerance is not observed by increasing the overall time from 12 to 15 days, provided tumour clonogen proliferation does not occur during the weekend split, the insertion of a gap makes continuous accelerated clinical regimes, currently given without an interruption at weekends, easier to introduce into wider clinical practice. PMID- 2268767 TI - Recent films and screens for mammography. PMID- 2268766 TI - Direct analysis of quantitative data from radiobiological studies on pig lung. AB - An alternative approach for the analysis of quantitative data, obtained from functional measurements, has been developed. The method does not require conversion of the quantitative measurements into quantal data thus defining a threshold level of effect. This method describes a parameter, equivalent to an iso-effective dose, which can be used for the comparison of different fractionation schedules by the assessment of lung function in radiobiological studies. The method only requires the use of a standard linear regression analysis and is therefore very simple to use. PMID- 2268768 TI - The antenatal diagnosis of congenital cystic adenomatoid malformation of the lung. PMID- 2268769 TI - Severe dwarfism with cataracts. A new osteo-chondrodysplasia. PMID- 2268770 TI - Paraganglioma of the duodenum: a case report with radiological findings and literature review. PMID- 2268771 TI - The scintigraphic detection of ossific mediastinal and pulmonary metastases in osteosarcoma. PMID- 2268772 TI - An unusual cause of abdominal pain. PMID- 2268773 TI - High surface temperature of endovaginal probes. PMID- 2268774 TI - [Pre-implant esthetic study]. AB - The first dental prostheses used on Branemark implants were aesthetically disappointing both for the dentists and their patients. Therefore the authors will consider the various aesthetic problems encountered when treating loss of teeth with implant systems. The problems related to resorption are numerous: large bone losses are resolved by adapting removable acrylic, carrying out bone transplants immediately fixed by the implants, using filling materials, or complete dentures fixed with attachments supported by the implants. Periodontal surgery often provides a solution to the problem of gum visibility at the level of the maxillary anterior teeth. The problems related to the site where implants emerge can often be avoided by consultation between the surgeon and the prosthodontist and by flexing a surgical guide compiled from a pre-prosthetic analysis of the clinical situation. The aesthetic problems related to the actual implant systems are dependent on three factors: When the prosthesis is directly screwed onto the implant, the axis of the implant determines the axis of the dental prosthesis and can lead to the emergence of the screw on the buccal surface; With angulated cores, orientated screws provide the required solution. The implant material, when metallic leads to an unsightly border at the gingival level. Ceramic implants, or the "ceraming" of titanium, provide a solution to this problem. In case of diastema the use of an implant system gives the best choice in comparison to the more conventional treatments. In conclusion, the authors point out the importance of pre-implant analysis which must give an evaluation of the aesthetic result. The fragility of the aesthetic evaluation should encourage dentists to obtain the "clear and written consent" of their patients, accepting the risks run by treatment of this kind. PMID- 2268776 TI - [Dental prostheses on implants in 1990]. PMID- 2268775 TI - [Periodontal requirements in osseointegrated and biointegrated implantology]. AB - Osseo or bio-integrated implantology has become the turning point in modern dentistry and every decision regarding treatment planning should take into consideration the possibility of implant, and combine the knowledge of specialists such as periodontists, implantologists and prosthodontists. The psychological, medical and local evaluation will decide about the choice of the right patient for implant in order to resolve a unit, partial or full edentation. The periodontal therapeutic of the residual teeth will be realized before any insertion of implants and will focus more on elimination of the periodontal diseases on teeth that should be maintained, that on the maintenance on the arches of teeth with poor prognosis. The early extraction of these teeth and their immediate replacement by implants are recommended on certain conditions. The two step procedure in surgical implantology should respect the biological principles in order to obtain and maintain the osseo or bio-integration. The objectives of the post-implantology periodontal treatment will not be limited only to the elimination of the pocket around the implant, but will also create an optimal environment of keratinized attached gingiva around the collar of the implant, necessary for functional and esthetic purposes. The prosthodontic treatment on implants will be conducted with care and according to the perio occluso prosthetic principles. It is finally essential to preserve the gingival health around the implant and to prevent a gingivitis to become a peri implantitis, by a regular maintenance and evaluation. PMID- 2268777 TI - [Place of implantology in the treatment plan: apropos of some clinical situations]. AB - The advent of osseointegrated implants has considerably influenced the treatment of the edentulism. The Branemark's protocol allows a high enough degree of predictability for a wide variety of clinical applications. A selection of the most typical indications attempts to focus on the benefit of implant supported prosthesis, regarding the conventional prosthetic treatment. The relative indications concern single-tooth replacement and Kennedy class III situations where classical tooth supported bridge is not easily feasible. The resort to osseointegration treatment enhances the possibilities of prosthetic rehabilitation in unfavorable conditions. The greater part of the indications is represented by Kennedy class I and class II situations. Clinical examples selected show the different combinations related to the fixtures position in the maxilla where bone availability is reduced. When just one fixture can be installed, connection with adjacent tooth must be carefully indicated. With two fixtures, a bridge must be designed with a posterior cantilever. But the opposite dentition can also dictate a fixture installation in the posterior region for a good occlusal stabilization: a specific modality of fixture installation in the pterygoid region has provided a seductive alternative. The last part concerns the prosthetic rehabilitation of advanced cases involving evolutive periodontal disease. The current trends determine a flexible approach with strategic extractions and progressive fixtures installation during stabilized periods of the disease activity. This management of the treatment planning reduces the psychogenic stress related to the complete edentulism and allows a easier transition from partial implant supported-prosthesis to fully bone anchored prosthesis. PMID- 2268778 TI - [Criteria for determining clinical success with osseointegrated dental implants]. AB - In the past decade, the technique of osseointegration has elicited three general responses in the dental profession. The first and major response has been an enormous clinical satisfaction to resolve difficult prosthetic problems, as well to expand the scope and range of routing prosthetic therapy. A second, if minor, response has been an attempt to deny the documented apparent superiority of the osseointegrated method. The third response has been a very active marketing one, which led to the rapid proliferation of a large number of implant systems, all claiming osseointegration and comparable success to the originally introduced Swedish system. The purpose of this paper is to describe and analyze those clinical criteria which can be used by dentist and researcher to determine the long term success or failure of functioning dental implants. Some attempts had been made to identify criteria which reflected sound scientific consideration of long term host acceptance of functioning implants. However, these criteria where a reflection of the state of the art information as perceived by the authors at the time. It is therefore fair to add that the principle of osseointegration did not feature in our colleagues recommendations. Since it is an axiom that host response must be analyzed and understood if a clinical technique is to be successfully prescribed, we regarded our own and other's published data on clinical results with osseointegration as pivotal in the grouping of criteria which would comprise a reliable yardstick, easy to identify and apply, and which reflected assessment experiences in dental practice and research, mainly in the disciplines of periodontics and prosthodontics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2268779 TI - [How to interpret success rates in implantology]. AB - How can almost every oral implant manufacturer claim success rate of nearly 100%, when clinicians are still in the process to include implants in their practice. Articles on long-term data are still scarce in the international Journals today. Often the different safety and effectiveness of various implant systems are based on the data that Professor Branemark started to collect 25 years ago. To interpret an article demands knowledge about study design, statistical analyses as well as type of diagram. There are number of important aspects to consider when reading a report on success rates. To understand why some studies can show almost 100% success rates for the upper jaws and others 80%, one must be aware of the important parameters which affect the results. In order to compare the results of one study with the results of another, these parameters, and how they are applied must be taken into consideration. PMID- 2268780 TI - [Hydroxyapatite coated dental implants. Biological criteria and prosthetic possibilities]. AB - Incorporating contemporary implant research and the most advanced principals of biomaterials and bioengineering puts HA-coated implant system into clinical practice. This system utilizes a streamline precision two-stage procedure similar to the swedish method and other osseointegrated systems to ensure complete fixation and an unloaded healing phase prior to the functional use of implants. The surgical concept has been theoretically improved upon by enhancing the titanium cylinders with a HA coating of 50 to 65 microns to the body. The advantages of HA have been extensively discussed. Research has shown that a biochemical reaction occurs between HA and bone and the interface between bone and ceramic is stronger than either the ceramic or bone alone. Bone adapts well to all biocompatible metals and bone will "chemically" bond to HA. An activated sintering process has been developed that enables HA to be chemically bound to the titanium cylinder using a modification of the plasma flame spray technology. This HA coating has been developed to meet the most rigorous biomechanical requirements for bonding in high stress applications of orthopedics as well as intraoral use. Biointegration is defined as "mechanochemical" clinically significant interface that predictably develops between vital load bearing bone and a bioactive calcium-phosphate ceramic metal such as HA. The design and planning of the HA-coated metal system also provides a variety of restorative choices and have been extensively discussed in this article. Clinical reports appear excellent, and the current implant system is into its fifth year of clinical use. The use of HA-coated implants has very well satisfied restorative needs as well as following sound biologic principle. PMID- 2268781 TI - [Dental implants and bone grafts]. AB - The reconstruction of an edentulous maxilla with bone graft is not a challenge. It is considered when the remaining bone cannot provide a firm anchorage for implants. The grafts are harvested from the ilium, the chin or the cranial vault. According to the case, the implants are placed either simultaneously or 6 months later after control with C.T. Scan. They are uncovered after another 6 month period, as in the usual procedure, and osseointegration is checked. The percentage of success on 24 operated cases seems at least equal to the regular cases without bone graft. Longer follow-up is needed for reliable statistics. PMID- 2268782 TI - [Functional prosthetic treatment for the partially edentulous with osseointegrated implants]. AB - The edentulous distal extension area has generally been restored with a removable partial denture. Some clinicians report long term success with a fixed partial denture containing distal cantilever pontic(s). Conversely, other clinicians find that the aforementioned is suspect at best due to the unusual stress demands placed on the abutment teeth by the pontic(s). When a tooth borne fixed partial denture is used to restore a long edentulous span, reports vary relative to long term success. The advent of osseointegrated implants as tooth substitutes may reduce and often eliminate particular compromised fixed or removable partial denture designs. Disregarding other problems that may or may not coexist with any remaining natural teeth in the same arch is a fallacious overview. It is paramount that future problems must be incorporated in any and all treatment plans at the same time the initial plan is formulated. Recent surveys reveal that a fewer percent of the population are becoming completely edentulous. Therefore, it is apparent that an increase in the treatment of the partially edentulous implant patient is a realistic consideration for all restorative dentists. However, it is ironic that those patients with the most severely debilitated conditions may often not be candidates for implant procedures. It is mandatory that a detailed explanation of any compromises and drawbacks to the final result must accompany the initial diagnostic presentation to the patient. It is quite evident that the dentist is confronted with a paradox that is difficult to resolve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268783 TI - [Occlusion in osseointegrated prosthesis]. AB - Occlusion plays a significant role in the successful restoration of natural teeth and in replacing missing teeth. Over the decades, standards for occlusion have been established. Implants, osseointegrated, have provided a rigid, usable abutment for restorations of occlusion and for the replacement of missing teeth. The natural tooth, due to it's mobility dynamics, presents problems related to occlusion. The osseointegrated, rigid implant, due to it's lack of mobility, presents in many respects problems related to occlusion. Substantial amounts of research has been presented on implants as it relates to success of osseointegration and acceptance by bone, and the acceptance of oral mucosal tissues to penetration of the implant. Failures of implant fixtures and their parts have been experienced. Not much information has been presented on the causes of failures. The question becomes obvious What is the role of the forces of occlusion? The purpose of this article is to present some aspects of occlusion that are important in restoring natural teeth and complete dentures. The problems in applying these aspects to the osseointegrated, rigid implant will be presented. The factors to consider in the control of the forces of occlusion in using implants will be established. It is not possible to cover all the possibilities of occlusion for implantation. However, the factors to consider in making intelligent choices will be presented. PMID- 2268784 TI - [Panorama of prosthetic options in osseointegrated implantology]. AB - Today, several prosthetic options can be used with osseointegrated implants. Fixed bridges may be retained by screws or cemented. Detachable bridges may be screwed on cylindrical, conical, straight or angulated abutments. In certain cases, they will be placed directly in contact with the implants. Cemented bridges may be placed over screwed, cemented or transfixed copings. They also may be cemented over transfixed metallic structures already splinting the implants. Removable prosthesis may be stabilized with bars, stud attachments or magnets. All these different options are discussed, and their advantages and disadvantages presented. PMID- 2268785 TI - [Analysis of bone-implant stress distribution. Finite element modeling]. AB - A two-dimensional finite element partial mandibular model allows a first comparison between two types of titanium cylindrical implants, one full, the other hollow. The study cases correspond to a distal edentulous rehabilitated with a three-unit bridge supported mesially by a healthy second premolar and distally by one of the two concerned implants. The model includes the mandible from the canine region to the condyle, and allow to investigate the interactions between implants and bone tissue, under a normal biting load (100 N) distributed over the different teeth of the model. On a general way, the highest stresses magnitudes are in the implants, so there are no pathologic actions in bone, even if the distal cervical region of the implants are more stressed than any place else of the alveolar bone. It is well known that bone resorptions are often found in that region. Furthermore the bone trunk of the hollow implant is no more stressed than the rest of the mandibular, that is good for bone affixing. The outcome of this work, over the first results exposed, is that it gives the opportunity to understand the complexity of such a problem. PMID- 2268786 TI - [Osseointegrated dental implants]. PMID- 2268787 TI - [Comparative analysis of different types of "implant-prosthesis" connection. Esthetic effect, prosthetic techniques]. AB - Thanks to the combined evolutions of surgery and of the concept of implantology it is now possible in the case of prosthetical rehabilitation to associate function, aesthetics and phonetics. The pre-prothetical analysis makes it possible to determine the various stages of an all-inclusive treatment namely: periodontics, surgery, prosthetics and occlusal equilibration, so as to obtain the appropriate results. The surgical problems caused by bone resorption in the toothless places are worsened by mechanical ones due to a deficiency in the parallelism of implants. Nevertheless the post-implants will be placed in the prosthetical corridor chosen before surgery. The aim of this article is to study the different types of junctions, permitting to link the implants to the prosthesis, whether it will be cemented of screwed. Depending on the clinical case, the choice of a connector, hence of a system of implants is determined by a number of questions such as: will it be easy to place the post-implants in the prosthetical corridor and to parallel them? Will it be possible to use systems permitting ductility or not? Is there any risk of the connector going loose? To what extent will the aesthetic function be respected? (Screw heads in the case of removable prostheses as well as gingival finishing lines of the superstructures). PMID- 2268788 TI - [Evolving in prosthetics with the Branemark system]. AB - The incorporation of the Branemark root-form osseointegrated implant into the practice of Prosthodontics has opened up a new range of treatment options previously unavailable to our patients. No longer limited to their original use in restoring the completely edentulous arch, the role of implants now includes the replacement of one or more missing teeth in partially edentulous situations. Implants may also be incorporated into periodontal prostheses as supplemental support where the number or strength of existing natural abutments is inadequate, and used as a means of salvaging prostheses which have failed as a result of the loss of strategically important abutments. These newer applications, however, combined with patient demands for the optimum in esthetics as well as function, have served to challenge our ingenuity and resourcefulness in this rapidly evolving field. The objective of this paper is to provide an overview of the evolution of our implant experiences in recent years, and to illustrate the ways in which the Branemark system has been utilized and adapted as the number and complexity of clinical situations have increased. Simply stated, the technical aspects of prosthetic treatment, those involving impression techniques, materials, etc., have remained fairly constant throughout our implant experience. The more dramatic changes have occurred through the utilization of newer components as they have become available, as well as through a growth in our application of the system and in our approach to treatment planning. The Branemark system has been in use for just over 25 years at this point in time and has proven itself to be reliable, predictable and at the same time versatile enough to admirably meet the challenges placed on us by the new and varied clinical situations we are now undertaking to treat. It is by using our imaginations to stretch the limits of the system without overstepping its boundaries that we have reached the point where osseointegration is truly becoming a part of our basic armamentarium in the practice of Prosthodontics. PMID- 2268789 TI - [Morphology of implant restorations in the cuspid area]. AB - Implant supported posterior restorations must be constructed following established prosthetic principles. The need for screw-retained abutments and the narrow diameter of root form implants dictate additional treatment protocols that fail beyond the scope of conventional prosthetics. Cemented restorations offer simplicity and good control of morphology, but can only be considered if no reservicing and removal of the restoration are anticipated. Screw retained restorations allow for reservicing on remediation but necessitate centering of the fastening screw within the occlusal anatomy. In case of implant misalignment, axis problems are solved with preangled or customized copings, or double frameworks. The diameter of root form implants is significantly smaller than posterior natural teeth and the emergence of the restorations must be progressively flared to achieve proper anatomy. Limited interocclusal space and implant placement may dictate restoring posterior teeth as premolars selecting a short abutment or a UCLA abutment, or overlapping the crowns over the soft tissues. The final selection is best assisted with a diagnostic waxing and with provisional restorations anticipating the completed treatment. PMID- 2268790 TI - [Implant-ceramometal prosthesis relation: esthetic and technical improvements]. AB - Two major concerns characterize the difficulties encountered with prostheses on implants. 1--The difference in orientation between the implant, imposed by anatomical requirements, and the restoration anatomy. It should be kept in mind that a sufficient occlusal space is required to house the restoration. The regularization of the occlusal curve of the opposite arch, in the example given, was obtained by bonding ceramic overlays. 2--The visibility of the abutment at the gingival level. In this clinical case, after removing the old prosthesis, it is observed that the position of the screws is unsuitable, as one of them emerges into the embrasure. A solution to these problems may be found in building an intermediate screwed core. The technical protocol requires the use of long screwed transfers, a specific impression method and plastic preforms. The intermediate core is formed by the combination of two hollow dowel cores into which a conventional metal ceramic bridge is incorporated. Aesthetically speaking, the prosthetic construction is characterized by the absence of metal visibility. The use of the pterygoid bone radically transforms prosthetic indications. It is advisable that the extremity of the implant remains accessible. Linking to the restoration can be carried out with a screwed telescopic substructure. It is not necessary, at the level of the pterygoid bone situated outside the limits of the arch, to carry out any dental morphology. A smooth, polished construction situated below the plane of occlusion is sufficient. PMID- 2268792 TI - Neurocardiology: an orphan discipline? PMID- 2268791 TI - Endothelin-1--marker or mediator of vascular disease? PMID- 2268793 TI - Coronary artery bypass profile in Canada and the United States. AB - This study compares computer registry data on coronary bypass surgery from several centres in Canada and the United States to assess current trends in patient profile, and looks at demand and resources available for this form of treatment. A computerized registry established at the Royal Victoria Hospital in 1982 was used to document the profile of patients undergoing coronary artery bypass graft. Comparing 1988 to the previous six years (1982-87), a significant increase was found in patients with unstable angina (P less than 0.001) and abnormal left ventricular function (P less than 0.015) among those operated. The incidence of emergency operations also increased (P less than 0.001). The patient profile was similar to that of the Toronto university hospital population and many major United States university hospitals. The incidence of coronary artery bypass graft per 100,000 population, however, is much greater in the United States than in Canada (120 versus 56). Resources in many Canadian centres appear to be insufficient to meet demand for this type of surgical intervention. PMID- 2268794 TI - Incidence and clinical significance of ST segment depression in supraventricular tachycardia. AB - To evaluate the clinical significance of ST segment depression observed during paroxysmal supraventricular tachycardia, the data of 100 patients who underwent electrophysiologic testing between 1981 and 1986 in the drug free state were reviewed. Twelve lead electrocardiograms were taken within 20 s of tachycardia induction. Patients with antidromic tachycardia, tachycardia using multiple accessory pathways or tachycardia associated with bundle branch aberration or concomitant electrolyte abnormalities were excluded from the study. Significant ST depression was defined as at least 0.1 mV horizontal or downsloping or 0.2 mV upsloping depression, measured 80 ms after the J point. ST segment changes were correlated with historical data and the results of exercise tests and radionuclide or coronary angiograms. There were 52 males and 48 females, aged 11 to 67 years (mean 32.8 +/- 13.2). Tachycardia was due to atrioventricular reentry via an overt or concealed accessory pathway in 85 patients, and atrioventricular nodal reentry in 15 patients. Significant ST depression was seen in 51 patients (aged 11 to 65 years). Thirty-three of 70 patients younger than 40 years old had significant ST depression. There was no relationship between the presence of significant ST depression and age, sex, mechanism or rate of tachycardia. Only three patients had significant coronary artery disease, and all manifested significant ST depression during tachycardia. Thus the specificity of this finding was 51% and the predictive value only 6%. In conclusion, ST segment changes observed during narrow QRS complex tachycardia are common, nonspecific and a poor predictor of underlying coronary artery disease. PMID- 2268795 TI - Angiographic features associated with acute coronary artery occlusion during elective angioplasty. AB - To examine the morphologic features of stenotic segments developing abrupt coronary occlusion during elective angioplasty, 36 cases occurring at the Toronto General Hospital between January 1985 and December 1989 were evaluated and compared with a temporally matched successful group. Quantitative arteriographic analysis was performed, including estimates of arterial tortuosity (proximal stenotic axis deviation) and qualitative assessment for dystrophic calcification, residual lumen eccentricity and intimal irregularity. Acute occlusion occurred more frequently in the mid-arterial segment (success, mid 14 versus occlusion 21, P less than 0.05). Stenosis severity assessed by minimum stenotic diameter did not affect outcome (success 0.42 mm versus occlusion 0.37 mm, not significant or relative percentage diameter stenosis (success 86% versus occlusion 86%, not significant). Average stenotic length was equal (success 14.3 mm versus occlusion 13.6 mm, not significant), although coronary arterial tortuosity was increased in the acute occlusion group (success 27 degrees versus occlusion 34 degrees, P less than 0.05). Residual lumen eccentricity score was increased (success 1.66 versus occlusion 2.69, P less than 0.001), with greater dystrophic calcification in the occlusion group (success 0.31 versus occlusion 0.69, P less than 0.05). In addition, intimal irregularity was significantly greater (success 1.65 versus occlusion 2.5, P less than 0.001), although major arterial side branches failed to predict outcome (success 28% versus occlusion 36%, not significant). These data suggested that a mid-coronary anatomic location, arterial tortuosity, lumen eccentricity, dystrophic calcification and intimal irregularity increased the probability of acute occlusion during elective coronary angioplasty. PMID- 2268796 TI - Effect of intracoronary nifedipine on coronary bloodflow and myocardial metabolism during pacing-induced ischemia. AB - The effects of intracoronary nifedipine on coronary bloodflow, its regional distribution, myocardial oxygen consumption and lactate metabolism during pacing induced angina were evaluated in 15 subjects. These responses were directly compared to 10 subjects who received an alcohol-based control solvent. Myocardial bloodflow was measured by thermodilution, with changes in regional coronary flow assessed using a dual radiolabelled (technetium-99m and indium-111) intracoronary microsphere technique and single photon emission tomography. Neither intracoronary nifedipine (100 micrograms) or the control solvent produced changes in systemic arterial pressure (nifedipine -2 mmHg and control +2 mmHg, both not significant). Intracoronary nifedipine markedly increased left ventricular end diastolic pressure (pre-nifedipine 13.0 mmHg versus post nifedipine 20.1, P less than 0.05), while increasing total coronary sinus bloodflow (pre-nifedipine 134 mL/min versus post nifedipine 189, P less than 0.05): Regional coronary bloodflow increased in all myocardial segments, regardless of the severity of coronary stenosis (64 to 132% baseline, all P less than 0.05). In addition, intracoronary nifedipine increased myocardial oxygen consumption (pre-nifedipine 12.3 mL/min versus post nifedipine 15.7, P less than 0.05), with a trend towards improved lactate extraction (pre-nifedipine 0.24 mg/mL versus post nifedipine 0.12, not significant). Although decreased ventricular afterload (left ventricular systolic wall stress) may contribute to nifedipine's antianginal properties, a primary increase in regional coronary bloodflow also appears to be an important factor in the alleviation of myocardial ischemia. PMID- 2268797 TI - Superiority of dipyridamole over exercise testing when exercise thallium imaging is limited by angina. AB - The extent of jeopardized myocardium can be underestimated on stress thallium myocardial perfusion images when exercise tolerance is limited by angina pectoris. A patient's tolerance for pain can influence the degree of myocardial ischemia observed on myocardial perfusion images during effort angina. A case is reported of a patient with angina pectoris showing mild ischemia limited to one myocardial segment on exercise thallium images, but severe and extensive reversible perfusion defects during dipyridamole-thallium imaging, and a 70% stenosis of the left main coronary artery on coronary angiography. PMID- 2268798 TI - Fatal left ventricular perforation following balloon mitral valvuloplasty. AB - Left ventricular perforation following a balloon mitral valvuloplasty is a rare complication. This paper reports morphological findings in such a case that was fatal. Cardiac tamponade was suspected clinically, but could not be confirmed or treated because of extensive anterior pericardial adhesions related to a previous closed mitral commissurotomy. PMID- 2268799 TI - Inspiratory reduction in left heart filling as a mechanism of pulsus paradoxus in cardiac tamponade. AB - Pulsus paradoxus occurs in cardiac tamponade because the output of the left ventricle falls during inspiration. The principal cause for this is reduced filling of the left ventricle during the preceding diastole. The present study examines whether this reduced filling of the left ventricle on inspiration is due to compression by the right heart or due to reduced venous return to the left heart. The effect of pericardial tamponade on hemodynamics and left ventricular and atrial volumes was determined in six experimental animals. The data demonstrate that from the outset pericardial fluid reduces left ventricular end diastolic volume, although initially left ventricular end systolic volume decreases as well. By contrast, pulsus paradoxus is a relatively late phenomenon occurring with severe tamponade and associated with an inspiratory decrease in left atrial and ventricular volumes in the face of a drop in left ventricular filling pressure. Underfilling of the left heart is the most likely cause of this combination of events. PMID- 2268800 TI - Clinical applications of programmed electrical stimulation of the heart. PMID- 2268801 TI - Retooling for the 90s or being born again in SPSS. PMID- 2268802 TI - Strategic planning for a Nursing Information System (NIS) in the hospital setting. Development of a Nursing System Model. AB - As nursing departments become more involved in automation, strategic planning for computer applications gains importance. Making the switch from manual to automated systems requires an understanding and analysis of the present system. This knowledge allows participants to examine the current information processing routines in relation to how well they support departmental goals. Priorities for projects can be established and alternatives for more efficient and effective information management schemes can be considered. The development of a Nursing System Model to serve this purpose is described. The model provides an overview for planning and identifies data classes created or used in nursing, organized according to the processes which act upon the data during the accomplishment of work activities. PMID- 2268803 TI - Computer applications for community health nursing educators. AB - Community health nursing clinical practicums present unique problems for the clinical teacher. Using a laptop computer and an integrated word processing, database management, and spreadsheet program enhanced the productivity of this clinical teacher and, consequently, the quality of clinical instruction. PMID- 2268804 TI - Maintaining student interest in CAI. AB - Students seem to be losing interest in computer assisted nursing instruction (CAI). CAI needs to be stimulating and motivating to promote optimal learning. This article presents four instructional design features of CAI that facilitate interest and motivation: objectives, attentiveness, individual control, and reinforcement. Authors of software should use these features in design and nurse educators should include these design issues when evaluating CAI for purchase. PMID- 2268805 TI - Care and feeding of nicad batteries. AB - The increasing popularity of laptop computers powered by nicad batteries has resulted in a greater number of people using them for the first time. This article describes the care of nicad batteries to provide maximum use of this expensive resource. PMID- 2268806 TI - Little packages with big power. A micro-network to meet nursing information needs. AB - Installation and use of microcomputer LANs is on the rise in health care facilities. The microprocessor is becoming more powerful each day. The microcomputer is quite adept at handling textual and graphic information, which is a major requirement of any nursing patient information system. Microcomputer technology has now advanced to a level where a handful of hospitals have installed, and many hospitals actively plan to install, a complete nursing system based entirely upon a network of microcomputers. This paper discusses components of an order entry/results reporting/care management system based on a distributed, micro network architecture; the benefits of such a design; and the future technology to aid in system use and growth. PMID- 2268807 TI - Dietary habits after ileal pouch-anal anastomosis. AB - Dietary habits of patients who had undergone ileal pouch-anal anastomosis were assessed and correlated with bowel function. Twenty-four well-adapted patients (11 women, 13 men; mean age 32 years) voluntarily entered the study 30 +/- 4 months after closure of the diverting ileostomy. A standardized questionnaire on 108 food items and a 3-day food journal were used in the assessment. Twenty-one patients had no difficulty in selecting an appropriate diet. Caloric intake was adequate. Specific symptoms associated with several foods were as follows: increased stool frequency (beer, spirits, chinese food), decreased stool consistency (beer, wine, fried fish), perianal irritation (spicy foods), undigested particles (grapefruit, lettuce), odours (eggs). Pasta and bananas were associated with increased stool consistency. The authors believe that these observations may help in dietary counselling after ileal pouch-anal anastomosis. PMID- 2268808 TI - Recurrent acute pancreatitis--rarely idiopathic: 1989 Du Pont lecture. AB - The majority (about 75%) of patients who suffer from acute pancreatitis do so as a consequence of gallstones or alcohol abuse. The other 25% of patients often present difficult diagnostic problems. Over several years the author has accumulated a series of patients with remedial causes of pancreatitis. They include a group of congenital conditions such as pancreas divisum, choledochal cysts and congenital abnormalities of the pancreatic ductal system. Patients who have had pancreatitis and who have an intact gallbladder often have stones that are difficult to identify. Repeated attacks of pancreatitis in the absence of any other apparent cause justifies cholecystectomy, which will often identify the cause so that recurrence can be prevented. A group of nonanatomic causes are also known. They include hyperlipidemia, drugs and toxins, certain systemic illnesses such as systemic lupus erythematosus, pregnancy, hypercalcemia, hereditary causes and occasionally cancer. In his lecture the author reviews the various etiologies of acute pancreatitis and describes an algorithm that can be used when the diagnosis is difficult. PMID- 2268809 TI - Early metabolic and neurologic predictors of long-term quality of life after closed head injury. AB - Research has begun to identify early markers that predict survival after traumatic brain injury. In this study, trauma and biochemical indicators of severity were used to predict quality of life in 61 adults with traumatic brain injury and no damage to other organ systems. Severity markers available within 24 hours of injury were predictive of later psychosocial, behavioural and social role functioning. Multiple regression analyses demonstrated that the Glasgow Coma Scale, plasma glucose levels, leukocyte cell count and serum potassium concentration accounted for 12% to 66% of variance in certain measures of later quality of life. The importance of health-care resource allocation and psychosocial and behavioural intervention to the outcome after moderate traumatic brain injury is discussed. PMID- 2268810 TI - Prosthetic replacement of the arthritic knee after patellectomy. AB - The results of total knee replacement with a semiconstrained prosthesis after patellectomy are poor because the stabilizing effect of the patella is lost. A series of bicompartmental unicompartmental knee replacements (five patients) carried out for this condition was compared with a series of Insall-Burstein posterior stabilized knee prostheses (six patients). If both cruciate ligaments are present the results are not notably different, but those with an Insall Burstein prosthesis generally fared better at stair-climbing using the replaced side as the lead leg. Since the Insall-Burstein knee is technically easier to implant there seems little to recommend the bicompartmental unicompartmental prosthesis in this condition. PMID- 2268811 TI - Perioperative cefazolin prophylaxis in hip fracture surgery. AB - Antibiotics given perioperatively are thought to decrease the occurrence of postoperative wound infection. The duration of treatment for hip fracture surgery is empirical. This randomized, double-blind, single-hospital clinical study was carried out to assess the effect of both antibiotic use and duration of use on wound infections in hip fracture surgery. Wound infection rates in three groups of patients were compared: those who received four doses of cefazolin (108 patients), those who received one dose of cefazolin and three doses of placebo (83 patients) and those who received four placebo doses (121 patients). Results showed an infection rate of 1.6% for the four-dose group, 2.4% for the one-dose group and 3.7% for the placebo group. These differences were not statistically significant, even when both treatment groups were combined and compared with the placebo group. The authors conclude that until more patients are added, empirical use of antibiotics should be continued in patients who undergo hip fracture surgery. PMID- 2268812 TI - Cesarean section in Ontario: practice patterns and responses to hypothetical cases. AB - A 40% random sample of Ontario's obstetricians were asked to respond to hypothetical scenarios for previous cesarean section, breech presentation and dystocia, and to describe their practice patterns. Their responses confirmed findings from other studies, which reported differences between physicians' responses to hypothetical cases and their actual practice. In this study, 18% chose a cesarean section for the hypothetical case of a patient who had previously undergone cesarean section and 2% chose a cesarean section for the hypothetical case of breech presentation. However, in practice, the obstetricians reported that they do cesarean section on 71% of their previous section patients and on 57% of their breech patients. Physicians in teaching hospitals were less likely than those in community hospitals to choose cesarean section for a woman who had previously undergone cesarean section both hypothetically and in practice. For breech presentation, no difference was found. The discrepancy between responses to the hypothetical cases and practice patterns could not be attributed to the absence of anesthesia services or to restrictive hospital policies. PMID- 2268813 TI - Augmentation ileocystoplasty in children with myelodysplasia. AB - Over the past 8 years 20 children suffering from myelodysplasia were selected to undergo augmentation ileocystoplasty for urinary incontinence refractory to treatment by clean, intermittent catheterization and anticholinergic agents, or as part of urinary undiversion. The children ranged in age from 5 to 17 years, and the follow-up ranged from 6 months to 7 years. Three children underwent undiversion, two had vesicostomy closure and six had bladder outlet repair at the time of augmentation. In one patient, surgery was technically impossible. Postoperatively 16 children were fully continent on clean, intermittent catheterization and anticholinergic medication. Three boys failed to achieve satisfactory continence. Delayed perforation, a potentially serious complication, occurred in two patients several months postoperatively. PMID- 2268814 TI - Perforated duodenal ulcer in the elderly patient. AB - Acute perforation of a duodenal ulcer in a patient over of 70 years of age is associated with a high death rate. During a 10-year period, 35 such patients were operated on; in all omentopexy was performed. Two courses of the disease were observed: the first (19 patients) was defined by acute disease of less than 24 hours' duration preceding surgery; the second (16 patients) was of longer duration, starting with various abdominal complaints and presenting more severely only after the first 24 hours. Postoperative death rates were 0% in the first group and 50% in the second. Other factors that were studied, including diabetes mellitus, presence of concomitant malignant diseases and intake of ulcerogenic drugs, had no significant effect on the outcome in these patients. PMID- 2268815 TI - Two heroes of the Class of Onety-Seven: Part II. AB - Frederick Banting and Norman Bethune were linked in time, place of birth, as classmates in medical college, veterans of World War I and heroes to different worlds. Both were surgeons, sharing the decisiveness that is characteristic of the profession. Both had their surgical ambitions frustrated. Banting, a failed orthopedist, was sidetracked to research; Bethune, a successful surgeon inactivated by tuberculosis, was directed by his interest in his disease to thoracic surgery. Frustrated in his battle for socialized medicine, Bethune went to war against the Fascists in Spain and the Imperialists in China. Banting discovered insulin, but did little else in original research. However, he organized research in Canadian universities which studied pilot safety in air warfare in World War II. The two heroes died within 2 years of each other, Bethune of an infection contracted at surgery on wounded Chinese soldiers and Banting in a plane crash while on a secret mission carrying his research results to Great Britain. PMID- 2268816 TI - Is multimodality therapy an option to surgery alone in adenocarcinoma of the gastroesophageal junction? PMID- 2268817 TI - Biliary colic. PMID- 2268818 TI - Kock to urethra: continent functional bladder replacement. AB - Since 1950 when Bricker first described the construction of the ileal conduit, this procedure has become a standard method of urinary diversion after pelvic exenteration. Recently, increasing interest in continent diversions has resulted in the development of several new procedures, using both small bowel and large bowel to produce and internal urinary reservoir. Such reservoirs still maintain a urinary stoma which requires periodic catheterization for emptying. With the development of the Kock low-pressure urinary reservoir, it has now become possible to re-establish the continuity of the urinary system by anastomosing this internal reservoir to the posterior urethra. This procedure utilizes the distal urethral sphincter as a continence mechanism and allows functional bladder emptying without a stoma. An antireflex valve is constructed to protect the kidneys. The authors report their experience with 20 such diversions, describing the operative technique, detailing the perioperative complications and providing urodynamic evidence of restored bladder function. PMID- 2268820 TI - Case management: a model of advanced practice? PMID- 2268819 TI - Pyloromyotomy of Ramstedt: experience of a nonspecialized centre. AB - In a general hospital over a period of 6 years 57 infants with congenital hypertrophic stenosis underwent a Ramstedt pylorotomy. In most cases a surgical resident-in-training performed the operation under the direct supervision of a general surgeon. There were no complications of anesthesia, no deaths and no substantial morbidity. The majority of infants left the hospital within 48 hours. The results in this series compared favourably with those reported from more specialized centres. PMID- 2268821 TI - Limited view of the profession of nursing. PMID- 2268822 TI - Nurses who practice under the title clinical nurse specialist. PMID- 2268823 TI - Clinical nurse specialist collaboration with physicians. AB - The nurse-physician relationship is the major dyad of the health care delivery system. The integration of the clinical nurse specialist (CNS) role in collaboration with physicians is an evolving style of practice reflecting collegial relationships. Various issues are associated with collaborative practice. Obstacles to collaboration between CNSs and physicians are addressed, followed by strategies to promote collaborative practice. Essential components of collaboration are identified. The impacts of collaborative practice on health care professionals and consumers are explored. Support for CNS and physician collaboration is validated by reports of CNS and physician collaborative practices. PMID- 2268824 TI - Increasing the precision of the analysis through the use of analysis of covariance. PMID- 2268825 TI - Maternal-infant clinical nurse specialist performance assessment: development of an evaluation tool. AB - The Maternal-Infant Clinical Nurse Specialist Performance Evaluation Tool was developed to assist students to enact certain role behaviors of the clinical nurse specialist (CNS) in maternal-infant nursing and to provide faculty with a measurement of such behaviors for the purpose of student clinical evaluation. Items for the behaviorally-anchored, criterion-referenced tool were derived from current standards of CNS practice, expected competencies of the CNS as reported in the literature, and program and course objectives. Initial use of the tool with graduate students in the maternal-infant specialty indicated a valid and reliable rationale for continued use. Since the categories of the tool represent common CNS roles, it should be applicable to other specialties. PMID- 2268826 TI - Maternal-infant clinical nurse specialist performance assessment: reliability and validity of an evaluation tool. AB - The Maternal-Infant Clinical Nurse Specialist Performance Evaluation Tool was used to evaluate the clinical performance of two classes of graduate students (n = 7, n = 4) enrolled in maternal-infant clinical practicums. When used by raters very familiar with the tool, i.e., those participating in its development, it yielded valid (.90) and reliable (.93) ratings of performance. When used by raters with limited familiarity with the tool, both validity and reliability declined but were still quite acceptable (.68 and .81, respectively). Better training for such raters should produce even more useful results. These results warrant continued cautious, monitored use of the tool in maternal-infant nursing. The generic content of the tool offers the possibility of its generalization to other specialties. PMID- 2268827 TI - The CNS and collaborative practice. PMID- 2268828 TI - Utilization pattern of clinical nurse specialists in the Baltimore-Washington area. AB - In the present cost containment environment, hospitals often change their employment patterns. Nurses in advanced practice roles are particularly vulnerable to reassignment. In order to determine if the employment of Clinical Nurse Specialists (CNSs) in the Baltimore-Washington area had decreased and to determine what specialty areas employed the most CNSs, a survey of all area hospitals was conducted. The nursing departments of all 88 hospitals were contacted by phone with 40 of them (45%) agreeing to provide data. Seventeen institutions reported employing a total of 119 CNSs. Of these, only 12 required a Master's degree for nurses to hold that position. As expected, larger institutions employed more CNSs. This role appears to be stable, with only two institutions having eliminated CNS positions recently and five reporting plans to add such positions in the near future. Most CNSs reported either directly or indirectly to the Director of Nursing. Those in positions funded by another source reported to personnel in the funding department or agency. Almost all CNSs had clinical titles, and Psychiatric, Oncology, Medical and/or Surgical, Pediatrics or Critical Care were the most prevalent specialties mentioned. The CNS role is a viable role in the Baltimore-Washington area even in this time of cost containment. Most CNSs are identified with their area of clinical specialization. PMID- 2268829 TI - Indices of success. PMID- 2268830 TI - Implementing Focus Charting: process and critique. AB - Documentation is an issue of importance to nursing for many reasons. Quality patient care depends upon complete and accurate information among care givers, third party reimbursement is based on documented care, inefficient documentation systems and behaviors are costly to an institution in terms of salaries, overtime pay and dissatisfied nurses, and documentation is an essential component of institutional licensure and accreditation. The authors describe documentation issues that prompted Christ Hospital of Oak Lawn, Illinois to revise their documentation system, selection of Focus Charting, the educational process for a nursing staff of 1200, and a critique of the educational process. Clinical nurse specialists played a key role in each step of the project. PMID- 2268831 TI - "Setting up a fee for service program for psychiatric liaison nurses". PMID- 2268832 TI - Setting up a fee for service program for psychiatric liaison nurses. AB - In the current health care climate, hospitals are under great pressure to find creative ways of preserving and generating revenue. As a result, all positions are routinely scrutinized for their value to the institution. Nurses have always been regarded as a major drain on the hospital's pocketbook, rather than as a revenue-generating resource. Because of their unique roles, liaison nurses provide many patient services which are third-party reimbursable. Practical guidelines for setting up a fee for service program are outlined together with the possible negative and positive repercussions of such a program. Enhanced job security and professional self-esteem may be offset by resistance from other disciplines and the possibility of a reduction in the volume of referrals. Although nurses who bill may face opposition from some groups, the ability to generate revenue is an important feature of this nursing role and is viewed as a strong asset by the institution. PMID- 2268833 TI - Malpractice litigation in health care today. PMID- 2268834 TI - Testifying in court: how to develop credibility with the jury. AB - As the number of health related lawsuits increases, the chance of clinical nurse specialists appearing in court increases. Clinical nurse specialists must realize that the key to winning in the courtroom may not depend on a point of law but rather on whom the jury views as the most trustworthy witness. The key is credibility! This article provides information that will enable clinical nurse specialists to develop credibility with the jury. It addresses such issues as what nurses' rights and responsibilities include, when it is appropriate to address the judge, how to keep a lawyer "honest," and specific ways a nurse can prepare to give testimony, including the deposition. PMID- 2268835 TI - [Psychiatric morbidity in patients hospitalized for AIDS: experiences in a Quebec hospital]. AB - Neuropsychiatric complications in AIDS patients are common and have been reported in many recent articles. The author reviewed the medical charts of 80 patients admitted for AIDS between April 1984 and April 1988 to determine the frequency and nature of psychiatric complications in these patients and to compare these with recent reports made by other authors. The most frequent complications requiring psychiatric intervention seem to be organic mental disorders and adjustment disorders. Practical conclusions are drawn. PMID- 2268836 TI - Treatment outcome for children and adolescents with conversion disorder. AB - This paper describes the clinical impressions of conversion disorders developed after long term in-depth clinical work with 137 children and adolescents and their families. Almost half of the 89 patients who were directly treated and followed by the author through an integrative child and family therapy approach recovered less than two weeks after the initiation of the treatment. Only three out of 89 patients required longer than four weeks for recovery. The rest responded well to the therapy and recovered with two to four weeks of treatment. Factors associated with positive treatment outcome are: younger age of patient, healthy personality characteristics, lack of psychopathology, insight and treatment compliance, healthy family functioning, acceptance by the family of the psychological nature of the illness, positive feelings towards the child and the family by the staff, lack of internal conflict and inflexible neurotic defences, and early therapeutic interventions. It was found that child and adolescent patients with conversion disorders responded quite well to an integrative, condensed treatment approach. PMID- 2268837 TI - A comparison of borderline and schizophrenic patients for childhood life events and parent-child relationships. AB - Fifteen patients with DSM-III diagnoses of borderline personality disorder and 14 schizophrenics were administered two questionnaires by an interviewer blind to the diagnoses. The questionnaires were the Childhood Life Events and Family Characteristics Questionnaire and the Parental Bonding Instrument. A scale to monitor denial was also included. Borderlines, when compared with schizophrenics, reported having significantly more childhood sexual and physical abuse, more early separation from their mothers, more paternal criminality, and also more paternal overprotection and less maternal care. When compared with normal population data, they received significantly less care and were significantly more overprotected by both parents. PMID- 2268838 TI - Attachment pathology and low social skills in avoidant personality disorder: an exploratory study. AB - The criterion of desire for affection and acceptance was eliminated from the definition of avoidant personality disorder in the DSM-III-R. But clinical experience in our setting suggests that attachment pathology related to such desires is an important diagnostic feature and a frequent focus of clinical intervention with avoidant individuals. Forty-seven patients receiving a clinical diagnosis of avoidant personality disorder completed a brief questionnaire which rated desire for an attachment relationship, fear of an attachment relationship and level of social skills. The results support our hypotheses that attachment security is distinct from general social skills and that desire for but fear of an attachment relationship is more characteristic of those diagnosed with avoidant personality disorder than a low level of social skills. PMID- 2268839 TI - Psychiatric ethics and ethical psychiatry. AB - This paper critically examines the code of ethics that applies to practising psychiatrists. The code performs the functions for which it was designed admirably well. It does not, however, resolve moral dilemmas (i.e., complex situations in which any course of action compromises certain ethical principles). In these cases, the psychiatrist must turn to wider moral theory (i.e., psychiatric ethics) for guidance. PMID- 2268840 TI - Effects of trihexyphenidyl on plasma chlorpromazine in young schizophrenics. AB - This study investigated the effects of trihexyphenidyl on chlorpromazine (CPZ) plasma levels and clinical state in 20 relatively young schizophrenic patients diagnosed using the DSM-III. Spontaneous changes in CPZ plasma levels over time were also examined. Trihexyphenidyl significantly increased CPZ plasma levels (average 41%) but did not produce clinical change. The trihexphenidyl-induced increase in CPZ plasma levels was independent of CPZ oral dosage and of CPZ plasma levels. Chlorpromazine plasma levels decreased non significantly (about 13%) over the four weeks following steady state, but there was marked inter subject variability, and CPZ levels rose in some subjects. Although identical CPZ doses produced widely variable plasma levels, CPZ plasma levels correlated significantly with oral dose. The views that antiparkinsonian drugs interfere with neuroleptic efficacy, and do so by lowering neuroleptic plasma levels, are questioned. PMID- 2268841 TI - Mania-like reaction induced by benzodiazepine withdrawal in a patient with mental retardation. AB - Symptoms resembling mania following withdrawal of diazepam in a mentally handicapped woman are described. The importance of considering benzodiazepine withdrawal in the assessment of acute behavioural disorders of the mentally handicapped is emphasized. Attention is also drawn to the paucity of research regarding the use of antianxiety drugs in the mentally handicapped. PMID- 2268842 TI - Research methods in psychiatry. PMID- 2268843 TI - Sample size and power in psychiatric research. AB - The conclusions drawn by study are susceptible to two types of errors. The more familiar one occurs when it is believed that there was a true difference between the groups or an association between two variables, when in fact this observation was due to chance (a Type I error). The second potential error consists of falsely concluding that there was no difference or association when indeed there was one (a Type II error). Most researchers know that the probability of a Type I error can be controlled by the setting of alpha level of statistical significance; however, many are unaware of methods to control or estimate Type II errors, based on estimates of an appropriate sample size. This paper discusses techniques researchers can use to calculate the sample sizes required for studies, and the effects of sample sizes which are too small or too large. If it is too small, there is an increased risk of a Type II error, whereas if it is too large, there may be a needless waste of time, money, and effort. The paper also discusses how readers of research articles can determine whether or not negative findings reported by a study are a true reflection of the lack of any difference between groups, or a result of insufficient sample size. PMID- 2268844 TI - Trends in treatment admissions for cocaine and other drug abusers. AB - This paper examines the proportion of drug abusers who report cocaine abuse as their primary problem at a Toronto clinic. In addition, characteristics of cocaine abusers are compared with those of alcohol and cannabis abusers. There is a significant increase in the proportion of drug abusers seeking treatment for cocaine use relative to other drugs, and a dramatic increase in their absolute numbers. Differences in age, marital status and socioeconomic status among cocaine, alcohol, and cannabis abusers are also noted. PMID- 2268845 TI - Chronic fatigue syndrome and the psychiatrist. AB - The number of patients who are identified as having chronic fatigue syndrome (CFS) has increased, and as a result, chronic fatigue syndrome has received widespread attention. Research has demonstrated that cognitive, affective and behavioural symptoms are prominent in CFS. Psychiatrists are therefore being asked to participate in the assessment and management of patients with this syndrome. This paper will provide an overview of the clinical characteristics of CFS and the current empirical findings related to its pathology, and will conclude with a discussion of the management of these patients. PMID- 2268846 TI - Trainee safety in psychiatric units and facilities. The position of the Canadian Psychiatric Association. PMID- 2268847 TI - Interaction between clonazepam and phenelzine. PMID- 2268848 TI - Patient's rights to review board hearings. PMID- 2268849 TI - Protein kinase activities in neoplastic squamous epithelia and normal epithelia from the upper aero-digestive tract. AB - In the present study the activities of three different protein kinase were determined in squamous cell carcinoma from the upper aero-digestive tract, and compared with the activities in normal oral mucosa. The protein kinases investigated are: a) cAMP-dependent protein kinase; b) cGMP-dependent protein kinase, and c) casein kinase II. The basal protein kinase activity, when histone IIa was used as substrate, was about 3-fold higher in tumors, as compared to normal mucosa, in the soluble fraction (32.0 +/- 4.2 and 10.9 +/- 2.4 pmol 32P/mg prot. X min, respectively). In the particulate fraction the basal protein kinase activity was about 9 times higher in tumors as compared to normal mucosa (19.4 +/ 5.2 and 2.1 +/- 0.3 pmol 32P/mg prot X min, respectively). The protein kinase activity in the presence of cyclic nucleotide (cAMP/cGMP) minus the basal protein kinase activity was taken as the cAMP- and the cGMP-dependent protein kinase activity, respectively. Maximal protein kinase activity was obtained in the presence of 0.5 microM of cyclic nucleotide both in squamous cell carcinoma and normal mucosa. In the cytosolic fraction the cAMP-dependent protein kinase activity was 33.9 +/- 13.0 pmol 32P/mg prot. X min in tumors, and 28.2 +/- 5.8 pmol 32P/mg prot. X min in normal tissue, after stimulation with 0.5 microM cAMP. The cGMP-dependent protein kinase activity was 5-10% of the cAMP-dependent protein kinase activity, and no concentration-dependent stimulation with cGMP was seen. The cGMP-dependent protein kinase activity in the presence of 0.5 microM cGMP was 2.4 +/- 1.3 and 1.8 +/- 0.6 pmol 32P/mg prot. X min in tumors and normal mucosa, respectively. Casein kinase II activity was determined only in the cytosolic fraction and was found to be 3-fold higher in tumors as compared to normal mucosa (31.8 +/- 5.2 and 8.6 +/- 3.5 pmol 32P/mg prot X min, respectively). This study shows a general increase in histone phosphorylation and casein kinase activity in neoplastic squamous epithelia compared to normal epithelia. No evidence for an increase in cyclic nucleotide dependent protein kinase activities in neoplastic squamous epithelia was found. This study thus supports the idea that phosphorylation/dephosphorylation reactions may play an important role in the control of cell growth, differentiation and proliferation. PMID- 2268850 TI - Preliminary studies of serum glycoconjugates in patients with cancer using the enzyme-linked lectin assay. AB - After primary analyses on the serum glycoconjugates of lung cancer and normal individual using the enzyme-linked lectin assay (ELLA) with 12 kinds of lectins, PHA and LCA were selected for further study in the sera of 8 kinds of cancers, 4 kinds of non-malignant diseases and a kind of postoperative cancer. It was found that the test values of 7 kinds of cancers with PHA or LCA were significantly higher than those of the normal (P less than 0.01); the values of 4 kinds of non malignant diseases with PHA were not higher (P greater than 0.05); the values of the postoperative cancer with PHA were obviously lower than those of the preoperative (P less than 0.02). The results showed that the serum glycoconjugates which can bind to PHA seemed related to the cancerous existence in human bodies. The significance of the findings was discussed. PMID- 2268851 TI - Metal ions modulate the effect of doxorubicin on actin assembly. AB - Doxorubicin (DXR) exhibits a significant activity in many human malignant neoplasms but, unfortunately, produces many undesirable cellular troubles which mainly lead to a severe dose-dependent cardiomyopathy. Many Authors had suggested that doxorubicin interacts with actin and affects the intracellular ion composition; following this reasoning, we studied the effect of doxorubicin on actin polymerization in vitro induced by different metal ions. In this paper we show that the negative action of doxorubicin on actin polymerization (inhibition of filament growth, reduction of polymer amount and polymer size at steady-state) is strongly ion-dependent. With this finding, we suggest that the direct action of antibiotic on actin assembly, in the presence of the drug-related changes in cytoplasmic electrolyte pattern, could become predominant in vivo. PMID- 2268852 TI - Response of lymphoid cells to thymic hormonal factors isolated from mouse thymus. AB - Thymic hormonal factors were isolated from mouse thymus by two methods. (1) Thymic cytosols in phosphate buffer saline were filtered through Sephadex G100 with 0.1 M NH4HCO3 (pH 8.0) as buffer and the protein peaks were collected. (2) Protein having thymosin activity (F5) was isolated from thymic cytosols after heat inactivation, salt fractionation and desalting on Sephadex G25. Molecular weights of all the proteins were determined on SDS-PAGE. Biological activity of thymic proteins was studied by in vitro and in vivo assays, using synthetic thymosin alpha 1 as the standard. Thymocytes treated with different thymic proteins showed maximum stimulation at 16 h of incubation period. Preincubation of the thymocytes with the thymic proteins and subsequent incubation with Con-A decreased the stimulation index. Incubation of spleen lymphocytes with thymic proteins increased the percentage of Tdt+ cells. The antitumor effects of thymic proteins carried out on animals having leukemia, showed statistically significant results. Clinically however, the antitumor effects of the thymic proteins alone and in combination chemotherapy were negligible at 1 mg/kg body weight dose level. PMID- 2268853 TI - Activity measurements in human tissues of the methotrexate molecular target: a novel fluorometric assay. AB - As DHFR is the main molecular target of MTX, a widely used anticancer drug, its level in human tissues is likely to be one of the factors determining tissue sensitivity towards this drug. Forty-one biopsies were analyzed for their DHFR activity by a convenient spectrofluorometric assay developed in our laboratory; this sensitive method proved to be suitable for measurements in very small human samples. Statistical analysis of the results showed that (i) DHFR activity is not an index of tumorogenicity, at least in the cases studied, (ii) tumorous extracts contain modulators of DHFR activity. PMID- 2268854 TI - [Calcium and hypertension]. PMID- 2268855 TI - Evaluation of aortic dissection by transesophageal echocardiography. PMID- 2268856 TI - [Variant angina which interacts with two phenomena: local hypersensitivity and abnormal response in the coronary tree to vasoconstrictor stimuli]. AB - The aim of the present study was to evaluate the vasomotion of the entire coronary tree in variant angina, particularly focusing the attention on the behaviour of the "non spastic" epicardial vessels, using a quantitative coronary technique. Two different groups of patients served as controls. The first group consisted of 10 patients with accessory nodal pathway but without any sign of myocardial ischemia (Group I). The second group included 8 patients with stable exertional angina pectoris and coronary artery disease (Group II). The third group (Group III) consisted of 16 patients presenting with variant angina and spontaneous or hyperventilation-induced (HV: 30 cycles/min for 5 min) ST segment elevation. All patients underwent coronary angiography before and 2 min after HV testing; the evaluation of the coronary diameters was performed on baseline and after HV. In Group III, the HV testing caused a 26 +/- 12% reduction of the "non spastic" coronary vessels, with the mean control diameter of 2.00 +/- 0.61 mm that decreased to 1.48 +/- 0.55 mm. The patients of Group I showed only a mild degree of vasoconstriction (9 +/- 6%) of the epicardial coronary vessels; the Group II patients, also, showed a moderate response to vasoactive stimulus (11 +/ 8%), with the mean control diameter of 2.36 +/- 0.69 mm that decreased to 2.09 +/- 0.65 mm. The greater amount of vasoconstriction showed by patients with variant angina was statistically significant compared to both control groups (p less than 0.001). A further analysis of the coronary vasomotion, in Group III patients, showed that the 6 patients with normal or near normal coronary angiograms exhibited a 34% reduction in the vessel diameter. The remaining 10 patients who presented with a diffuse atherosclerotic involvement of the epicardial vessels (organic stenosis greater than or equal to 50% at the site of spasm) showed a lesser (20%) but yet significant extent of vasoconstriction compared to both control groups (p less than 0.001). In conclusion, our data indicate that: patients with variant angina exhibit a marked and diffuse coronary narrowing of the coronary vessels during vasoconstrictor stimuli; focal spasm occurs more frequently at the level of atherosclerotic coronary segments, whether they are critical or not. An interaction between these 2 phenomena, ie atherosclerosis and abnormal vasoconstriction, is supposed to be a cause of the occurrence of focal coronary spasm in variant angina. PMID- 2268857 TI - Transesophageal echocardiography for the diagnosis of thoracic aorta aneurysms and dissections. AB - The diagnosis of acute aortic pathology is decisive for the prognosis of the patient, since an effective surgical and medical therapy can improve the high rate of mortality due to this pathology. Conventional transthoracic echocardiography (TTE) fails to detect abnormalities of the descending thoracic aorta. Aim of this study was the evaluation of the actual usefulness of transesophageal echocardiography (TEE) in the diagnosis of aneurysm (AN) and/or dissection (DISS) of the aorta. Fifty-six consecutive patients with clinical suspicion of AN or DISS underwent TEE. Of these, 24 (42.8%) did not show any abnormality, while 32 (57.2%) had a severe pathology of the aorta requiring angiography (ANG) or cardiac surgery (SURG). All the patients underwent computed tomography scanning examinations (CT) even if TEE did not show any abnormality. The diagnoses obtained by TTE, TEE and CT were compared with those obtained by reference methods (ANG and/or SURG). Non-dissecting aorta aneurysms were detected in 11 patients; dissecting aorta aneurysms were found in 21 patients; 5 patients showed an isolated aortic dissection (without aneurysm). The sensitivity of TTE for detecting pathology of the aorta resulted very low (56.3%) when compared to TEE (96.8%) and CT (90.6%). The specificity for diagnosing aortic pathology was for TTE 63.1%, for TEE 96.0% and CT 88.8%; the accuracy of TTE resulted 75.0%, TEE 98.2% and CT 94.6%; the predictive value of TTE was 85.7%, TEE 96.8% and CT 93.5%. In conclusion, TEE provides a reliable non-invasive diagnosis of AN and/or DISS superior to TTE and CT; it may be considered the method of choice to detect acute aorta pathology. PMID- 2268858 TI - [Pathophysiologic classification of heart failure: contribution of echocardiography]. AB - Aim of the study was to examine the role of echocardiography to classify patients with heart failure. Fifty-seven subjects (32 dilated cardiomyopathy (DCM), 9 aortic regurgitation (AR), 16 hypertensives (HT)--4 in Class (CI) NYHA I, 24 II, 15 III, 14 IV--were studied by M-2D echo. Eighty-seven normals (N) were the control group; 11 were controlled after clinical improvement (3.4 +/- 3.8 months); 11 after worsening (12 +/- 17). We have evaluated: left ventricular diastolic dimension (LVIDd), wall thickness/radius ratio (H/R), diastolic (D) and systolic volume (S Vol), ejection fraction (EF), systolic arterial pressure/end systolic volume ratio (P/V), and stress. LVIDd and stress were increased in all groups; H/R reduced, except in HT and in Cl I; EF and P/V reduced except in Cl I. Between I and II LVIDd was different; between II and III all parameters were different, between III and IV only EF and P/V. According to regression S-D Vol, EF-P/V and EF-stress we identify the reduction of EF and the related mechanisms, ie reduced contractility or increased afterload. Thus, according to P/V and stress, we classify the patients in 4 pathopysiologic classes: 1 and 2 with P/V within 2 SD N: 1 with stress within 2SD N, EF and H/R normal; 2 with stress greater than +2SD, H/R normal and EF reduced; 3 and 4 with P/C less than -2 SD N: 3 with normal, 4 with stress greater than +2 SD. In the 1 and 2, 1 out 14 is in III Cl NYHA, none in IV; in 3,6 out 8 are in II, in 4, 9 out 35 are in Cl less than III. In the follow-up, in 8 of the improved patients, EF and P/V were increased and stress reduced; in 3, EF was reduced. In 8 of the worsened, EF and P/V were reduced, LVIDd and stress increased; in 3 EF and LVIDd were increased, P/V reduced. This study demonstrates discordance between Cl NYHA and echo, and how classification of NYHA does not give information about the several components of heart failure. However LVID and EF are not sufficient. By a correlation of echo-parameters of contractility, afterload and pump performance, we may suggest a classification of heart failure in pathophysiologic classes. PMID- 2268859 TI - Congenital lymphangiectasia of interventricular septum. AB - A case of congenital lymphangiectasia of ventricular septum obstructing outflow tract is reported. It mimicks hypertrophic cardiomyopathy or a primary tumor of the heart. Surgical operation has been successful and the expected prognosis is good. PMID- 2268860 TI - [Echocardiographic diagnosis of rupture of the interventricular septum and release into the wall of the left ventricle (with formation of pseudoaneurysm) in inferior myocardial infarction]. AB - A case of inferior myocardial infarction in a 77 years old woman suffering from angina pectoris for 8 years, is reported. The clinical course was complicated by mild heart failure secondary to interventricular septum repture, diagnosed by Doppler-echocardiography. The patient was discharged in III-IV NYHA class with medical therapy. Then, unstable hemodynamic conditions and episodes of angina pectoris occurred again. Five months after acute myocardial infarction, echocardiography confirmed the interventricular septum defect. An echocardiographic control, performed 17 months after the acute episode, documented, besides previous data, the presence of a pseudoaneurysm of the inferior wall with a large cavity in communication with the left ventricle. PMID- 2268861 TI - LDL-cholesterol as a determinant of coronary heart disease. AB - The Adult Treatment Panel of the National Cholesterol Education Program identified high levels of LDL-cholesterol as a major risk factor in developing CHD and as the primary target for cholesterol-lowering therapy. Low levels of HDL were recognized as a contributing risk factor for CHD, and the panel recommended that low HDL-cholesterol levels be raised by changes in diet and lifestyle. When drug therapy is required for high LDL-cholesterol levels in the presence of low HDL levels, it would appear reasonable to choose one that both markedly reduces LDL-cholesterol and raises HDL-cholesterol. PMID- 2268862 TI - Double-blind crossover comparison of ketoprofen, naproxen, and placebo in patients with primary dysmenorrhea. AB - Sixty-three women, aged 18 to 39 years, with primary dysmenorrhea received 25 mg, 50 mg, or 75 mg of ketoprofen, 500 mg of naproxen, or placebo as a first dose at the onset of moderate or severe pain. Each patient received three treatments and each treatment was tested in 36 patients. Mean pain relief scores (on a five point scale) indicated a significant analgesic response for all active treatments; superiority over placebo was shown by ketoprofen 50 mg for six hours, by ketoprofen 75 mg for five hours, by ketoprofen 25 mg for four hours, and by naproxen for four hours. The onset of pain relief and peak relief were reached faster and pain relief lasted longer after 75 mg and 50 mg of ketoprofen than after 25 mg of ketoprofen or 500 mg of naproxen, which in turn were superior to placebo. Treatment was rated good to excellent by 20 patients after 25 mg of ketoprofen, by 26 after 50 mg, and by 28 after 75 mg, and by 22 after naproxen and 11 after placebo. The incidence of side effects was similar in the ketoprofen treated and naproxen-treated patients. PMID- 2268863 TI - Effects of simvastatin, an HMG-CoA reductase inhibitor, on plasma lipids and steroid hormones. AB - Seven hyperlipidemic postmenopausal women received 2.5 mg of simvastatin daily for six months, 5 mg for four months, and 2.5 mg for two months. During treatment, there were significant decreases in the patients' levels of plasma total cholesterol, phospholipids, low-density lipoprotein cholesterol, apolipoprotein (apo) B, apo E, and in the ratios of low-density lipoprotein:high density lipoprotein cholesterol and apo B:apo A-I. Levels of high-density triglycerides increased significantly. Blood pressures tended to decrease. No significant changes in the plasma levels of cortisol, adrenocorticotropic hormone, testosterone, progesterone, or plasma renin activity were noted. Plasma aldosterone levels decreased significantly after nine months of treatment, but remained within normal limits. No other treatment side effects were recorded. PMID- 2268864 TI - Antihypertensive and metabolic effects of nitrendipine in hypertensive diabetic patients. AB - The subjects were 15 patients, aged 53 to 74 years, with noninsulin-dependent diabetes mellitus and mild to moderate hypertension. Each received 20 to 40 mg of nitrendipine daily for six months. Mean supine blood pressures decreased significantly from 177/102 mmHg before treatment to 164/95 mmHg at three months and continued to decline during the following three months. Diastolic blood pressure was reduced to less than 90 mmHg in eight of the 15 patients. No changes in heart rate, glycemic control (serum levels of glucose, C-peptide, glycosylated hemoglobin, and fructosamine), or serum lipid levels (cholesterol and its lipoprotein fractions, triglycerides, and apolipoproteins A1 and B) were noted. It is concluded that nitrendipine is safe and effective in the treatment of hypertension in diabetic patients. PMID- 2268865 TI - Evaluation of patients' preference of two potassium chloride supplements: Slow-K and K-Dur. AB - Eighteen patients (mean age, 66 years) who were receiving oral potassium supplements while being treated with diuretics were enrolled in this study. The patients were randomly assigned to receive Slow-K, a wax-matrix tablet, or K-Dur, a microencapsulated tablet, for two weeks and then the other drug for an additional two weeks; the daily dose was two to four tablets, equivalent to 20 to 40 mEq of potassium. Patients were asked to complete a survey about their compliance and preference ratings of both products. Of the 17 patients who completed the study, 14 stated that they preferred Slow-K to K-Dur and one preferred K-Dur to Slow-K; 14 patients made positive comments about Slow-K and seven made positive comments about K-Dur. The most common positive comment about Slow-K was its small size and ease in swallowing. Adverse reactions (mostly gastrointestinal) were reported by five patients during treatment with Slow-K and by six during treatment with K-Dur; three patients treated with K-Dur and none treated with Slow-K discontinued treatment because of adverse reactions. PMID- 2268866 TI - Treatment of community-acquired lower respiratory tract infections with oral cefuroxime axetil. AB - The subjects were adult hospitalized patients, 12 with pneumonia and eight with acute bronchitis. The patients with pneumonia received 500 mg of cefuroxime orally twice daily and the patients with bronchitis received 250 mg twice daily. Treatment lasted for ten days in responsive patients. The pathogens identified in the patients' sputum were Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Enterobacter aerogenes, Staphylococcus aureus, or Branhamella catarrhalis. Clinical and bacteriologic cures were achieved in 11 of the 12 patients with pneumonia and in seven of the eight patients with bronchitis. It is concluded that cefuroxime axetil is safe and effective in the treatment of community-acquired pneumonia or acute bronchitis. PMID- 2268867 TI - A multicenter trial comparing the efficacy and safety of cefuroxime axetil and cefaclor in pneumonia of adults. AB - The 185 hospitalized patients (aged 19 to 95 years) with pneumonia were randomly assigned to receive 500 mg of cefuroxime axetil orally (250 mg q12h), 1,000 mg of cefuroxime axetil orally (500 mg q12h), or 1,500 mg of cefaclor orally (500 mg q8h), daily, for a mean of nine days. Among the 151 evaluable patients, clinical cure was noted in 58% of the 500-mg cefuroxime axetil group, 94% of the 1,000-mg cefuroxime axetil group, and 88% of the cefaclor group, and clinical improvement in 32%, 4%, and 9%. Bacteriologic outcome was similar in the three groups. Adverse events were minor and comparable among the treatment groups. Cefuroxime axetil is a safe and effective oral antimicrobial for the treatment of pneumonia in adults. PMID- 2268868 TI - Clinical significance of the androgenicity of progestins in hormonal therapy in women. AB - Optimal efficacy has been achieved in both oral contraception and postmenopausal replacement therapy. The current challenge is to minimize the side effects and metabolic impact of the administered hormones in both oral contraceptives and hormone replacement agents. When the dose of estrogen in oral contraceptives was reduced the risk of thromboembolism decreased, but the androgenic side effects of the progestin became increasingly apparent. The addition of progestins to hormone replacement therapy reduces the risk of endometrial cancer associated with unopposed estrogen, but their androgenicity offsets the favorable effects of estrogen on lipid metabolism. Androgens not only cause troublesome clinical side effects but also induce changes in blood levels of lipoproteins that have been associated with an increased risk of atherogenesis and coronary heart disease, as well as alterations in glucose and insulin levels. Both the side effects and the adverse effects on lipoprotein and glucose metabolism can be reduced by the use of less androgenic progestins. PMID- 2268869 TI - Milestones in clinical pharmacology. Obesity. PMID- 2268870 TI - From cloning to a commercial realization: human alpha interferon. AB - Recent applications of recombinant DNA techniques have enabled the cloning of several interesting human genes, leading to the production of rare biologicals in abundant quantities. We review here the discovery, early characterization, cloning, and expression of Interferon Alfa-2B (IFN alpha-2b or Intron A) as a therapeutic at Schering-Plough Research. IFN alpha-2a is marketed by Hoffman LaRoche under the trade name Roferon. The studies on the expression, purification, biology, and clinical aspects of this interferon offer a plethora of information on one of the earliest recombinant DNA based drugs to reach the market place. PMID- 2268871 TI - Autoregulatory factors of secondary metabolism and morphogenesis in actinomycetes. AB - The Gram-positive bacterial genus Streptomyces possesses interesting biological aspects, such as the ability to produce a wide variety of secondary metabolites and a mycelial form of growth that culminates in sporulation. A close relationship of secondary metabolism and cell differentiation has been well recognized; secondary metabolism might be a physiological expression of cell differentiation. A variety of diffusible low-molecular-weight chemical substances have been found to function in general as regulatory factors, like "hormones" in eukaryotes, for secondary metabolism and cell differentiation. Among these factors, A-factor has been most extensively studied. This review summarizes recent research on the chemical structures, functions, biosyntheses, and mode of action of these regulatory factors. PMID- 2268872 TI - Roles for replicative deactivation in yeast-ethanol fermentations. PMID- 2268873 TI - Dynamic properties of intermediate filaments: disassembly and reassembly during mitosis in baby hamster kidney cells. AB - A morphological analysis of the organizational changes in the type III intermediate filament (IF) system in dividing baby hamster kidney (BHK-21) cells was carried out by immunofluorescence and immunoelectron microscopy. The most dramatic change occurred during prometaphase, when the typical network of long 10 nm-diameter IF characteristic of interphase cells disassembled into aggregates containing short 4-6 nm filaments. During anaphase-telophase, arrays of short IF reappeared throughout the cytoplasm, and, in cytokinesis, the majority of IF were longer and concentrated in a juxtanuclear cap. These results demonstrate that the relatively stable IF cytoskeletal system of interphase cells is partitioned into daughter cells during mitosis by a process of disassembly and reassembly. This latter process occurs in a series of morphologically distinct steps at different stages of the mitotic process. PMID- 2268874 TI - The iris diaphragm model of centriole and basal body formation. AB - This paper suggests that the formation and structure of the microtubular skeleton of centrioles and basal bodies can be derived from the following simple geometric principle. A closed ring of nine microtubular initiation sites defines (1) a template for the packing of 18 additional microtubular initiation sites, and (2) the shape of nine rigid arms. Upon swivelling of each arm around a point located four initiation sites away on the initial ring, the array unfolds in a manner similar to the opening of an iris diaphragm. As a consequence, the curved shape of the microtubular triplet blades arises together with the clockwise rotational sense of the slanted blades of the centriole or basal body. The final diameter of the centriole (basal body) self-adjusts. Furthermore, the pitch of the triplet blades, the taper of centrioles and basal bodies, and the change of slant of the blades towards the distal end can be derived. In addition, the model points to a method of replication of pro-centrioles (pro-basal bodies). The hypothesis was tested by the fitting of electron microscopical cross sections of centrioles of 3T3 cells to the geometric shapes predicted by the model. PMID- 2268876 TI - Myosin II antibodies inhibit the resorption activity of isolated rat osteoclasts. AB - We present microinjection data in support of an indirect approach by which cytoplasmic protein interactions important in the processes of bone resorption can be elucidated. Three polyclonal antibodies (M1, M3, M5) raised against myosin II from perfused rat liver differently affected the actin-activated Mg ATPase of myosin II. These antibodies microinjected into isolated rat osteoclasts affected osteoclast morphology and activity in bone resorption. M1, which completely inhibited myosin ATPase activity at a antibody:myosin ratio of 10:1, initially promoted the extension/retraction motility of lamellipodia but eventually reduced the spread area of osteoclasts along the substrate after 20 hr. M3, which inhibited ATPase activity by 70%, had similar effects; however, M5, which weakly inhibited ATPase activity, neither promoted extension/retraction nor reduced spread area of osteoclasts. Immunofluorescence showed that these antibodies removed myosin II from the majority of actin filaments in injected osteoclasts. Because antibodies that did not bind to a myosin II column had little effect on the extension/retraction of lamellipodia or the osteoclast spread area, these data suggest that myosin II participates in the stabilization of osteoclast lamellipodia along the substrate. M1 injection strongly inhibited injected osteoclasts from excavating resorption lacunae in bone slices, compared to control antibody. M3 and M5 were less effective but also inhibited bone resorption. These data show that myosin II is functionally important in bone resorption and that the osteoclast-differentiated activity of bone resorption is a more sensitive assay for myosin activity than lamellipodia motility or cell morphology. PMID- 2268877 TI - Measles in Canada-1989. PMID- 2268875 TI - p34cdc2 kinase is localized to distinct domains within the mitotic apparatus. AB - Antibodies to both the C-terminal and the N-terminal regions of the 34 kd serine threonine specific protein kinase, p34cdc2, were used to study the distribution of this protein in dividing cells and isolated chromosomes of the Indian muntjac. p34cdc2 was found to be present throughout the cytoplasm of dividing cells. In addition, a portion of cellular p34cdc2 was localized to the centrosome, kinetochore, and intercellular bridge and along kinetochore-to-pole microtubules during cell division. Tubulin-denuded metaphase kinetochores retained their association with p34cdc2. The detection of p34cdc2 within a variety of domains of the mitotic apparatus, in addition to the previous reported association with the centrosome [Bailly et al., EMBO J. 8:3985-3995, 1989; Raibowol et al., Cell 57:393-401, 1989] suggests that p34cdc2 may play a role in events associated with anaphases A and B as well as with the transition between interphase and mitosis. PMID- 2268878 TI - Are the alternatives to municipal waters truly safer? PMID- 2268879 TI - From temperature regulation to rhythm research. PMID- 2268880 TI - Photorefractoriness and its termination in the subtropical house sparrow, Passer domesticus: involvement of circadian rhythm. AB - Groups of photorefractory female subtropical house sparrows, Passer domesticus, when treated with 6 weeks of a short photocycle (8L:16D) showed significant ovarian growth on their return to a long photocycle (15L:9D). A 6-hr photophase coupled with scotophase of varying durations does not terminate the refractory period under photoperiod cycles of 12 (6L:6D), 36 (6L:30D) and 60 (6L:54D) hr but the refractory period is terminated by light-dark cycles of 24 (6L:18D), 48 (6L:42D) and 72 (6L:66D) hr. These results are consistent with the Bunning hypothesis of coincidence between endogenous photosensitive rhythmicity and environmental photoperiod timing that an endogenous circadian rhythm is involved in the maintenance and termination of photorefractoriness. PMID- 2268881 TI - Time-dependent effects of trichloroethylene on motor activity in rats. AB - Circadian variations in acute and subacute neurobehavioural effects of trichloroethylene (TRI: 1.2g/kg i.p.) were investigated in the rat under a light: dark = 12: 12 hr cycle. An acute effect of TRI evaluated by decreased muscle tone was maximal during the early dark phase (21:00). A subacute effect of TRI was evaluated by a continuous recording of spontaneous locomotor activity in the rat. The circadian rhythm in spontaneous locomotor activity was extensively impaired by the injection of TRI for three consecutive days. Spectral analysis of spontaneous locomotor activity showed that ultradian periods became more dominant than the circadian period, and the 1/f fluctuation of the spectrum disappeared after the injection of TRI. The effect of TRI on the circadian rhythm in spontaneous locomotor activity was circadian-phase dependent, and the treatment of TRI at 09:00 provoked greater circadian rhythm impairment than that at 21:00. The mechanisms of the time-dependent effect of TRI on neurobehaviour are the subject of further investigation. PMID- 2268882 TI - Multiple component analysis of plasma growth hormone in children with standard and short stature. AB - Growth hormone (GH) concentrations (in ng/ml) were determined by radioimmunoassay, in plasma obtained at about 3-hr intervals during a 24-hr sampling span, from 42 boys and 12 girls of short stature (2-4 standard deviations below their peer group mean), and 13 boys and 9 girls of standard stature. Subjects had 11.20 +/- 0.37 years of age at the time of study, and were living on a diurnal waking (approximately 07:30 to approximately 22:30), nocturnal resting routine during sampling. Analysis of these data by single and population-mean cosinor methods as well as by analysis of variance revealed circadian and ultradian prominent components characterizing most groups. Accordingly, a multiple component analysis was undertaken for data of each group separately, as well as for all subjects. A comparison of circadian parameters indicates similar characteristics between short and standard children, whether one compares boys [P = 0.674, 0.371 and 0.749 for comparison of rhythm adjusted means (M), amplitudes (A) and acrophases (phi), respectively], girls (P = 0.993, 0.914 and 0.397), or all children (P = 0.859, 0.712 and 0.865). Differences are found, however, in circasemidian characteristics as well as in the prominent 8-hr ultradian component documented for the short but not for the standard children. These ultradian components should be taken into consideration in the design and later evaluation of a time-specified treatment of children of short stature. PMID- 2268883 TI - Circadian characteristics of plasma cortisol in children with standard and short stature. AB - Cortisol (CT) concentrations (in micrograms/dl) were determined by radioimmunoassay in plasma obtained at about 3-hr intervals during a 24-hr sampling span from 42 boys and 13 girls of short stature (2-4 standard deviations below their peer group mean), and from a reference group of 11 boys and 10 girls with standard stature, before any treatment were administered to the former. Subjects were 11.20 +/- 0.37 years of age at the time of study, and were living on a diurnal waking (approximately 07:30 to approximately 22:30), nocturnal resting routine during sampling, consuming the usual hospital diet. Circadian rhythm parameters were computed separately for each group by the single and population-mean cosinor fits of a 24-hr cosine curve. A comparison of circadian parameters indicates a statistically significant difference in acrophase (phi; P = 0.033) between short and standard children, as well as added differences in rhythm-adjusted mean (M; P = 0.011) and phi (P = 0.035) between boys and girls of short stature. These differences, as well as any other added information from relevant marker rhythms, should be taken into account for the time-specification of therapy before treatment starts in children of short stature. PMID- 2268884 TI - The relation of age to the adjustment of the circadian rhythms of oral temperature and sleepiness to shift work. AB - The relation of age to the adjustment of the circadian rhythms of oral temperature (T0) and sleepiness (S) in shift work was studied. 145 healthy female nurses underwent detailed laboratory and field measurements. Self-rated sleepiness, and oral temperature measured with a special extended-scale mercury thermometer, were recorded at 2 hr intervals during a morning (M) and 2 consecutive night (N) shifts. Sleeping times were registered during the same days. The results were analyzed separately in the age-groups of 22-29, 30-39 and 40-49-year-old subjects. From the morning shift to the second night shift day, the oral temperature and sleepiness acrophases shifted significantly (p less than 0.001) forward in all age groups. The amplitude decreased in the youngest and in the 30-39-year old age groups but not in the oldest age group. During the second night shift day, the acrophases and amplitudes of oral temperature rhythms were significantly different (P less than 0.05) between the groups, but there were no significant differences by age in the change of the circadian rhythms from morning to the second night shift days. The results thus fail to corroborate that physiological adjustment to night work would be influenced by age. PMID- 2268885 TI - Computerized chronothermodynamic breast examinations under ambulatory conditions. AB - A new approach to the assessment of breast health was developed based upon continuous ambulatory recording of breast temperature for 24 hrs. A new data acquisition system consisting of a portable, multi-channel, microprocessor-based recorder worn on a belt was developed to record temperatures. Dramatic thermal fluctuations were noted during the recordings in response to multiple stimuli (physiological, behavioral, environmental). Specific algorithms and software programs were developed to process the thermobiologic and chronobiologic information. Data processing was fully automatic and included an examination report indicating a score and a chronothermodynamic class for each of the five areas examined on each breast. The preliminary clinical studies have concerned more than 450 patients with healthy or diseased breasts. PMID- 2268886 TI - Age and seasonal variation in serum testosterone concentration among men. AB - Serum testosterone concentrations from 4.462 military veterans, ages 32-44, were examined for age and seasonal variation. Testosterone concentrations were assayed from a single serum sample from each subject. All samples were drawn before breakfast, at about 8:00 a.m., from subjects recruited over a 16-month study period. Mean levels declined with age (P less than .001), from 864 ng/dl at age 32 to 602 ng/dl at age 44. Mean levels also varied with month of testing (P less than .01), with a seasonal peak in December (the seasonal peak was in November for men in their early 30s). The age effect was greater than the seasonal effect. Both effects may bear upon behaviour and should be treated as possible sources of error in studies of testosterone. PMID- 2268887 TI - Seasonal characteristics of and age at menarche. AB - Data from approximately 600 U.S. women were analyzed for seasonality in menarche. Data were converted to the ratio of observed (O) to expected (E) cases, based on an equal distribution of events over the year, per considered time span of the year. The greatest O/E ratio in menarche (1.55) occurred during January, followed by August (1.43) and July (1.24). The lowest O/E ratio in menarche occurred in February and May (0.68). Seasonal patterns in menarche were detected for the separate cohorts of women born during the 1940s, 1950s, and 1960s, with a shift from a December-January peak in menarche for those born in the 1940s and 1950s to an August-September peak for those born in the 1960s. Girls who were younger (8 14 yrs) at menarche exhibited a seasonal difference in the peak number of menarches by about 6 months in comparison to the pattern for girls who were older (15-17 yrs). Girls who experienced menarche during August-October were statistically significantly younger (p less than 0.05) than those born during the other three seasons. Season of birth was not statistically significantly associated with season of menarche. Overall, no 12-month pattern was substantiated by cosinor analysis in the month of menarche. However, a 6-month rhythm was detected in menarche for women born between 1940 and 1960 (p = 0.004, A = 29% M, phi = January and July). PMID- 2268888 TI - Circadian profile of serum melatonin in Cushing's disease and acromegaly. AB - We evaluated the circadian profiles of serum melatonin (MT) and cortisol in 6 patients with Cushing's disease while those of serum MT and GH were evaluated in 8 patients with acromegaly. The control group consisted of 15 healthy subjects in whom MT, cortisol and GH were determined. The presence of a circadian rhythmicity was validated by the cosinor method, while the diurnal and nocturnal amount of MT secretion were expressed in terms of area under the curve. Gross alterations of MT rhythm were not apparent in Cushing's patients. In acromegalics, we observed a blunted day-night oscillation of MT accounted for by a significant increase of its secretion during the day-time period. PMID- 2268889 TI - 24-hour profiles of blood pressure and heart rate in Cushing's syndrome: relationship between cortisol and cardiovascular rhythmicities. AB - We monitored the circadian profiles of cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P less than 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control. PMID- 2268891 TI - Synthetic anthracyclines: regiospecific total synthesis of D-ring thiophene analogues of daunomycin. AB - The key anhydride 2-acetoxy-[2-carboxy-5-(trimethylsilyl)thiophen-3-yl]acetic acid anhydride (8), prepared from (2-carboxythiophen-3-yl)acetic acid (5), underwent a strong base-induced cycloaddition reaction with the chloroquinone acetal (11) to give the 7,7-ethylenedioxy-2-trimethylsilyl-6,7,8,9- tetrahydroanthra[2,3-b]thiophene-5,10-dione (12) regioselectively. Similarly, the regioisomeric 8,8-ethylenedioxy-2-trimethylsilyl-6,7,8,9-tetrahydroanthra[2,3-b] thiophene- 5,10-dione (30) was obtained by the strong base-induced cycloaddition reaction of 8 with the chloroquinone acetal (29). These cycloadducts (12 and 30) were converted to D-ring thiophene analogues (28 and 38) of daunomycin (1a). Another D-ring thiophene analogue (42) which has a trimethylsilyl substituent in the D-ring was also prepared. PMID- 2268890 TI - Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities. AB - To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2 receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed. PMID- 2268892 TI - Stereoselective reactions. XVIII. Synthesis and cytotoxicity of the demethyl derivatives of steganes. AB - Demethyl derivatives of steganes and deoxypodorhizon, 3, 4, 6, 7, 9, 10, 12, 13, 18, 23, were prepared by the selective demethylation of the methoxy group of steganes and deoxypodorhizon, 2, 5, 8, 11, 22. The cytotoxicity of these derivatives was evaluated against KB cell and was found not to exceed that of the parent steganes. 4-Demethyldeoxypodorhizon (18) was found to show more potent cytotoxicity than deoxypodorhizon. PMID- 2268893 TI - Studies on orally active cephalosporin esters. V. A prodrug approach for oral delivery of 3-thiazoliomethyl cephalosporin. AB - Oral delivery of 3-thiazoliomethyl cephalosporin 1 was attempted through a prodrug approach by applying thiamine chemistry. The 3-thiazoliomethyl group was modified to a ring-opened structure with no ionic charge, and the 4-carboxyl group was converted to pivaloyloxymethyl ester. Lipophilicity of the resulting derivatives (8-10) was suitable for passive absorption from the intestinal tract, and chemical stability in phosphate buffer solution (pH 6.86) was moderate. When administered orally to mice, these derivatives were mainly transformed to a novel 3-spiro cephalosporin 11, and desired reconversion to the 3-thiazoliomethyl cephalosporin was minor. Isomerization to delta 2-cephalosporin 14 was also observed. These results showed that the derivatives (8-10) tested in this study did not serve as orally active prodrugs of 3-thiazoliomethyl cephalosporin 1. PMID- 2268894 TI - 62Cu-labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate for regional plasma volume measurement: application of new 62Zn/62Cu generator system. AB - 62Cu-Labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate was performed using a newly developed 62Zn/62Cu generator system. HSA-DTS was easily labeled with 62Cu, by simple mixing with 62Cu-generator eluate. In vivo blood clearance of 62Cu-HSA-DTS was similar to 131I-HSA, indicating the high applicability of 62Cu-HSA-DTS as a method for plasma volume measurement. In a positron emission tomography study of a dog, a clear plasma pool image of the head region was obtained. PMID- 2268895 TI - Chemical conversion of corticosteroids to 3 alpha,5 alpha-tetrahydro derivatives. Synthesis of allotetrahydrocortisol glucuronides and allotetrahydrocortisone glucuronides. AB - The synthesis of the 3- and 21-glucuronides of allotetrahydrocortisol (allo-THF) and allotetrahydrocortisone (allo-THE) is described. 5 alpha-Dihydrocortisol (5) was prepared by selective hydrogenation of 21-acetoxy-3, 11 beta, 17 alpha trihydroxy-3,5-pregnadien-20-one 3-ethyl ether (3), followed by acid hydrolysis and saponification. When 5 alpha-dihydrocortisol 21-tetrahydropyranyl ether (6) was treated with potassium tri-sec-butylborohydride in tetrahydrofuran under mild conditions, regioselective and stereoselective reduction at C-3 took place to give allo-THF 21-tetrahydropyranyl either (7). This compound was converted into the 3- and 21-monoacetates of allo-THF and allo-THE, key intermediates. Introduction of the glucuronyl residue at C-3 or C-21 was carried out by means of the Koenigs-Knorr reaction. Prior to saponification yielding the 3-glucuronides (20,23), the alkali-sensitive ketol side chain at C-17 was protected as 20 semicarbazones. PMID- 2268896 TI - Concentration and degradation of hyaluronic acid in knee synovial fluid from carrageenin-induced rabbit arthritis. AB - The concentration and degradation of hyaluronic acid in the synovial fluid of carrageenin-induced arthritic joints of rabbits was studied. A 0.5-ml volume of 1% lambda-carrageenin was intra-articularly injected three times into a right knee joint, and saline into a left. After 5 d from the last injection, inflammatory changes were observed in the synovial membrane and synovial fluid, but not in the articular cartilage. In the inflammatory synovial fluid, lipid peroxide content, phosphatase activity and cell counts were significantly increased, but the copper concentration was not changed. Concentration of polymeric hyaluronic acid and total hyaluronic acid were determined by high performance liquid chromatography using gel-permeation columns. Total hyaluronic acid was appreciably decreased in the inflammatory fluid. The polymeric hyaluronic acid determined was 38% of the total hyaluronic acid in the inflammatory fluid and 74% in the control fluid. This suggests that in the inflammatory fluid, molecular weights of hyaluronic acid are distributed in the broader range. The concentration of chondroitin sulphates was similar in both the inflammatory fluid and the control fluid, but the content ratio of chondroitin sulphates to hyaluronic acid was higher in the inflammatory fluid. In the inflamed synovial membrane, synthesis of hyaluronic acid as measured by incorporation of [14C]glucosamine into glycoconjugates was increased by about twice that in the control membrane. PMID- 2268897 TI - Studies on the optimal immunization schedule of experimental animals. V. The effects of the route of injection, the content of Mycobacteria in Freund's adjuvant and the emulsifying antigen. AB - The effects of several conditions for the immunization of mice was studied using an aliquot of a viomycin (VM) protein conjugate as the common primary or booster antigen. Responses of the mice were assessed by measuring mouse serum levels of total immunoglobulin G (IgG) and anti-VM antibody responses using the newly improved two assay methods. The choice of route was found to be a very important factor in immunization and intraperitoneal injection was the most optimal among the four routes studied. The effect of the concentration of Mycobacteria in Freund's complete adjuvant (FCA) was also studied, and it was found that a diluted FCA was more effective than a commercial FCA. The effect of the controlled release of the antigen was studied and three important phenomena were observed: The mice immunized by the mini-osmotic pump-aided controlled release of the antigen responded with similar small amounts of both total IgG and anti-VM antibody regardless of the presence or absence of FCA in the antigen; emulsifying the antigen with FCA was a very important condition for the effective elicitation of the specific antibody; a mixture of antigen and FCA without emulsifying produced little specific antibody and a large amount of total IgG. The more effectively immunized mice responded with a larger decrease in body weight soon after the primary injection. PMID- 2268898 TI - Inhibitory effect of validamine, valienamine and valiolamine on activities of carbohydrases in rat small intestinal brush border membranes. AB - Three pseudo-aminosugars, validamine, valienamine and valiolamine, produced by Streptomyces hygroscopicus subsp. limoneus showed potent inhibitory action on rat small intestinal carbohydrase activities such as sucrase, maltase, glucoamylase, isomaltase and trehalase activities, but negligible action on lactase activity and pancreatic alpha-amylase activity. Where inhibition was seen, kinetic analysis showed fully competitive inhibition of the carbohydrase activities by all three inhibitors. Valiolamine has more potent carbohydrase inhibitory activity than validamine or valienamine, and the apparent Ki values of valiolamine for sucrase, maltase, glucoamylase, isomaltase and trehalase activities were 3.2 x 10(-7), 2.9 x 10(-6), 1.2 x 10(-6), 9.1 x 10(-7) and 4.9 x 10(-5) M, respectively, which are 10(-5) to 10(-3) times smaller than the apparent Km values. PMID- 2268899 TI - Population pharmacokinetics of phenytoin from routine clinical data in Japan: an update. AB - Routine clinical pharmacokinetic data collected from outpatients receiving phenytoin (PHT) were reanalyzed to estimate population pharmacokinetic parameters. There were 756 steady-state PHT concentrations and associated dosage rates (mg/d) from 334 outpatients. The data were analysed using nonlinear mixed effects model (NONMEM), a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The influence of weight, co-anticonvulsants on the maximum elimination rate (Vm) and age, co-anticonvulsants on the Michaelis-Menten constant (Km) and the influence of dosage form on the bioavailability (F) of PHT were investigated. The Vm and Km of a 60 kg adult outpatient treated with PHT alone were estimated to be 325 mg/d and 2.41 micrograms/ml, respectively, while for a same size individual taking PHT with co-anticonvulsants respective estimates were 351 mg/d and 3.18 micrograms/ml. The parameter of a power function of weight was estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.737 power. The Km for patients less than 15 years old was 24.8% less than that of adults. Assuming the F of PHT to be 1 in patients prescribed a tablet, the F value in patients prescribed a powder was [1-exp(-9.92/Dij)]; Dij is the daily dose of PHT for the ith Cpss in the jth patients (mg/kg/d). PMID- 2268900 TI - Hypoglycemic effect of intestinally administered monosaccharide-modified insulin derivatives in rats. AB - The effect of the modification of insulin (INS) with p-succinylamidophenyl (SA) alpha-D-glucopyranoside (SAPG), SA-alpha-D-mannopyranoside and SA-alpha-L arabinopyranoside on the enzymatic degradation and the hypoglycemic effect in rats was studied. When SAPG-INS was administered intraintestinally in the absence of bile and pancreatic juice, blood glucose level decreased to 56% of initial value. Other monosaccharide derivatives were less effective than SAPG-INS. The digestion of monosaccharide derivatives by pepsin and chymotrypsin indicated that the resistance of insulin to enzymatic degradation was increased by its modification with monosaccharide. One possibility for the hypoglycemic effect of SAPG-INS could be the increased resistance of insulin to enzymatic degradation as a result of its modification with monosaccharide. PMID- 2268901 TI - Influence of tabletting speed on compactibility and compressibility of two direct compressible powders under high speed compression. AB - To examine the influence of tabletting speed on compactibility and compressibility under high speed compression, two direct compressible powders, alpha-lactose monohydrate and microcrystalline cellulose of different particle size ranges were compressed using an instrumented rotary press with varying tabletting speed and compression force. The maximum applied force and total time during compression (contact time) were determined from a time-force profile, and the relation between these parameters and properties of compacts was examined. For all lactose tablets, the porosity and tensile strength of compacts were less affected by compression rate though they depended on the applied force. However, the properties of microcrystalline cellulose tablets were varied depending on the tabletting speed in addition to the applied force. In an attempt to quantitatively evaluate the effect of compression rate on the compactibility, an empirical equation was derived from the numerical analysis of the experimental data. The compactibility parameters deduced from the equation well elucidated the effect of tabletting speed on the properties of microcrystalline cellulose tablets and lactose tablets made of various particle size powders. PMID- 2268902 TI - Effect of interpolymer complex formation on bioadhesive property and drug release phenomenon of compressed tablet consisting of chitosan and sodium hyaluronate. AB - The bioadhesion property of tablets consisting of chitosan (CS) and sodium hyaluronate (HA) was investigated using a lyophilized porcine dermis as a model of mucous membrane. Release phenomena of brilliant blue FCF (BBL) from the CS-HA tablets were also studied. BBL was employed as a model compound of water-soluble drugs. Strong adhesion forces were observed when the tablets were prepared from HA alone or a physical mixture of CS and HA. The adhesion of CS tablets was also obtained but it was rather weak. No effect of pH values in the media was observed on the adhesion force in these tablets. On the other hand, the release rate of BBL from CS-HA tablets was greatly affected by the change of the polymer mixing ratio, suggesting a possible interaction between CS and HA in the tablet following water penetration into the tablet. PMID- 2268903 TI - Stability and degradation pattern of cefpirome (HR 810) in aqueous solution. AB - The stability and degradation pathways of a new semi-synthetic cephalosporin, 1 [[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-ox o-5-thia-1 azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) sulfate (cefpirome sulfate, HR 810), were studied. Cefpirome in various buffer solutions was allowed to stand at 40 degrees C and its degradation patterns were investigated by high performance liquid chromatography. Cefpirome was stable in the region of pH 4-7 and slightly unstable beyond this range. In aqueous solution from the neutral to alkaline regions, the produced degradation products were: 1- [[(6R,7S)-7-[2-(2-amino-4 thiazolyl)glyoxylamido]-2-carboxy-8-oxo -5-thia-1-azabicyclo[4.2.0]oct-2-en-3 yl]methyl]-6,7-dihydro-5 H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O methyloxime) (epi-cefpirome); 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido] 2-carboxy-8-ox o-5-thia-1-azabicyclo[4.2.0]oct-3-en-3-yl]methyl]-6,7-dihydro-5H-1 pyridinum hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) (delta 2-cefpirome); 2 [[(2-amino-4-thiazolyl)((Z)-methoxy-imino)acetyl]amino]acetaldehyde; and 6,7 dihydro-5H-1-pyrindine. On the other hand, 1-[[(6R,7R)-7-[2-(2- amino-4 thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3 yl]methyl]-6,7-dihydro-5H-1-pyridinium++ + hydroxide, inner salt, 7(2)-(E)-(O methyloxime) (anti-cefpirome), 2-[[(2- amino-4-thiazolyl)-((Z)-methoxyimino) acetyl]aminomethyl]-1,2,5,7- tetrahydro-7-oxo-4H-furo[3,4-D]-[1,3]thiazine, and 6,7-dihydro-5H-1- pyrindine were produced in strongly acidic solution or under irradiation by artificial sunlight. PMID- 2268904 TI - Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. IV. Study on reduced-pressure mixing for practical use of amorphous mixtures of flufenamic acid. AB - Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) at a reduced pressure of about 10 to 50 mmHg employing a commercial mixer for pharmaceutical production. An amorphous state of FFA in the mixture was efficiently achieved with this equipment, and the dissolution of FFA was enhanced in comparison with that of the physical mixture. Effects of the conditions of mixing, such as pressure, temperature and rotating speed, on dissolution of FFA were determined. Through stability tests at 40 degrees C under both dry and humid conditions, no change in dissolution profiles was recognized in a 5% FFA mixture stored under any conditions. On the other hand, decreases in dissolution behavior were observed in 10% and 20% FFA mixtures when they were stored under humid conditions. These results suggested that humidity should be avoided during the storage of amorphous mixtures of FFA with MAS for production purposes. PMID- 2268905 TI - Salivary excretion of 5-fluorouracil (5-FU). V. Effect of 5-FU concentration in perfusate on the salivary excretion of 5-FU in perfused rat mandibular gland. AB - The effect of 5-fluorouracil (5-FU) concentration in the perfusate on the salivary excretion of 5-FU was investigated in the rat mandibular gland perfused with modified Ringer solution containing pilocarpine (10 microM). The saliva to venous-effluent concentration ratio (S/E ratio) of 5-FU increased gradually during the perfusion. The 5-FU concentration in the perfusate ranging from 10 to 200 micrograms/ml caused elevation in the mean value of S/E ratio. This non linearity suggested that the present perfusion method would be useful to further investigation for the mechanism of salivary excretion of 5-FU, since the tendency of the non-linearity was similar to that in in vivo studies as reported previously. The salivary flow rate declined with time, and the greater mean value of the flow rate was obtained during perfusion with the perfusate containing the lower level of 5-FU. Statistically significant correlation was found between the S/E ratio of 5-FU and salivary flow rate (p less than 0.01). Therefore, in the perfused rat mandibular gland, it was concluded that 5-FU itself had an influence on the salivary excretion of 5-FU via decreasing salivary flow rate. On the other hand, the salivary clearance of 5-FU showed no distinct increase and/or decrease not only with time but also with the change of 5-FU concentration in the perfusate. It seems to result from the cancellation of the increased S/E ratio of 5-FU by the decreased salivary flow rate in perfused rat mandibular gland. PMID- 2268907 TI - Synthesis and antibacterial activity of the metabolites of 9-fluoro-6,7-dihydro-8 (4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251). AB - The metabolites of 9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo 1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7251) (1), which has a potent antibacterial activity against gram-positive bacteria, characteristically Propionibacterium acnes, were synthesized to confirm their structures and to examine their antibacterial activity. The structures of three major metabolites (2, 3a and 4) were identified by means of comparison with the synthetic compounds. The antibacterial activity of the metabolites (2, 3a and 4) was found to be lower than that of 1. PMID- 2268906 TI - Inhibitory effect of fumaric acid on hepatocarcinogenesis by thioacetamide in mice. AB - The inhibitory effect of fumaric acid (FA) on hepatocarcinogenesis was examined in mice fed thioacetamide (TAA). A group of male ICR mice was fed TAA at a level of 0.035% in the diet for 40 weeks and then fed a basal diet for 48 weeks. Hepatic tumors developed in 11 of the 24 animals of this group and they were diagnosed as hepatocellular carcinomas. However, cirrhotic lesions and the enlargement of hepatocyte nucleoli were not as marked in mice as in previous findings in rats fed TAA. The effect of FA on the carcinogenesis was examined in a group of mice fed this compound at a level of 1% in a basal diet after ingestion of TAA. The inhibitory effect of FA on TAA carcinogenesis was so marked that no hepatic carcinomas were found in any of the 15 animals fed FA in combination with TAA. PMID- 2268908 TI - Antianoxic action and active constituents of atractylodis lanceae rhizoma. AB - The screening test was carried out to identify new drugs from natural products for the KCN-induced anoxia model in mice. Acetone extract of Atractylodis Lanceae Rhizoma (Atractylodes lancea DC. var. Chinensis Kitamura) had a significant effect in the KCN-induced anoxia model and therefore the extract was selected for further study in order to identify the active principles. The result showed that beta-eudesmol was the active component in Atractylodis Lanceae Rhizoma. PMID- 2268910 TI - Synthesis of 16 alpha-hydroxyandrost-4-ene-3,17,19-trione and 3 beta, 16 alpha dihydroxyandrost-5-ene-17,19-dione; potential intermediates of estriol biosynthesis. AB - 16 alpha-Hydroxyandrost-4-ene-3,17,19-trione (10) was synthesized from the 16 alpha-hydroxy-6 beta,19-epoxy-17-one 3 via protection of the 16 alpha-hydroxy function as its tert-butyldimethylsilyl ether or acetate. Reductive cleavage of the epoxy ring of the silyl ether 4 or the acetate 5 with zinc dust gave the 19 alcohol 6 or 7, which was treated with pyridinium dichromate or Jones reagent, respectively, and then hydrolyzed with diluted sulfuric acid, yielding the desired steroid 10. 3 beta,16 alpha-Dihydroxyandrost-5-ene-17,19-dione (14) was also synthesized from 5 alpha-bromo-3 beta,16 alpha-diacetoxy-6 beta, 19 epoxyandrostan-17-one (11) through the intermediates 12 and 13 with the 3 beta- and 16 alpha-hydroxy functions protected as their acetates in a reaction sequence similar to that above. PMID- 2268909 TI - Enhancement of the mutagenicity of Trp-P-1, Trp-P-2 and benzo[a]pyrene by bupleuri radix extract. AB - Boiling-water extract of Korean-Saiko (Bupleuri Radix, from South Korea, Bupleurum falcatum L.) enhanced the mutagenic activity of Trp-P-1, Trp-P-2 and benzo[a]pyrene with S9mix. The boiling-water extract was fractionated with ether and then n-BuOH. Both the ether and the n-BuOH fractions also enhanced mutagenicity of Trp-P-1, respectively. The n-BuOH fraction was separated into seven fractions by silica gel chromatography and the chloroform eluate had the strongest enhancing effect on the mutagenic activity of Trp-P-1 with S9mix. The chloroform eluate fraction was further separated into five spots by thin-layer chromatography. Two of the spots had the strongest enhancing effect on the mutagenic activity of Trp-P-1. Since saikosaponin is a well known component in Bupleuri Radix, the effects of its existence were tested and saikosaponins a and c were found. The enhancement activity of saikosaponin a was very weak. The effective components are now being studied. PMID- 2268911 TI - New fluorogenic substrates for microdetermination of cathepsin C. PMID- 2268912 TI - SPS-B, a physiological sleep regulator, from the brainstems of sleep-deprived rats, identified as oxidized glutathione. AB - We previously reported regarding the "sleep-promoting substance (SPS)," which was isolated from the brainstem extract of sleep-deprived rats, the existence of multiple active components including uridine and SPS-B. Intracerebroventricular infusion of crude SPS-B exhibited significant enhancing effects on both slow wave sleep and paradoxical sleep in unrestrained rats. Further investigation of SPS-B has resulted in its final identification as oxidized glutathione (GSSG, gamma glutamylcysteinylglycine disulfide). Authentic GSSG similarly administered in rats also significantly enhanced sleep which was indistinguishable from normal physiological sleep. We propose GSSG as a candidate endogenous sleep substance. PMID- 2268913 TI - Synthesis and inhibitory activity of isoindolinone derivatives on thromboxane A2 analog (U-46619)-induced vasocontraction. PMID- 2268914 TI - [Effect of the regimen of kidney-tonifying and qi-invigorating on aging changes of glucocorticoid receptor]. AB - The plasma cortisol concentration and the sites of glucocorticoid receptor (GCR) in the peripheral lymphocytes were measured in 32 healthy aged persons and 13 young adults. In animal experiment, GCR of spleen lymphocytic cell was also measured in 18 aged rats and 9 young rats. The results showed that GCR was significantly lower in the aged persons or rats than that in the young while the plasma cortisol level didn't change with aging. So we think that GCR is more sensitive than the plasma cortisol level to reflect the aging change of the adrenal cortex function. After the treatment with the regimen of Kidney-tonifying and Qi-invigorating, the GCR of the aged persons and rats was enhanced, and in this way, the function of the aged adrenal cortex was improved. PMID- 2268915 TI - [Antisenility effect of ginseng-rhizome saponin]. AB - Ginseng-Rhizome is the Rhizome of Panax ginseng and popularly named "Shenlu". The treatment group treated with the sugar-coated tablets of Ginseng-Rhizome saponin (GRS) orally for two months, one tablet (50 mg per tablet), three times a day. Through the clinical observations of 358 cases of middle and old age persons (age from 50 to 85 years old). The results showed that GRS possessed antisenility effect and marked effect on relieving the symptoms of aging, adjusting organic metabolism and improving physiological function, etc., such as promoting memory, raising the amount of white cells and improving organic immunity function. GRS both improved the function of hypophysisgonad axis and the function of adrenal cortex. It had marked efficacy in the treatment of coronary heart disease with angina pectoris and had better effect on treating concomitant atrial and ventricular prematures. The control group (123 cases, age from 50 to 85 years old) was given sugar-coated tablets of placebo (starch) for two months and then compared themselves with before. There were both no difference in clinical symptoms and experimental tests. After two years experimental researches and clinical observations, it showed that GRS tablet and Shenlu tablet both have no side effect of vomiting and also no toxic effect when they were taken for a long term. PMID- 2268916 TI - [Urine excretion of PGE2, PGF2 alpha in patients with deficiency-cold syndrome and deficiency-heat syndrome]. AB - The 3 hours' urine excretion of PGE2 and PGF2 alpha in 32 patients and 19 healthy persons were determined by RIA. According to TCM, the patients were divided into two groups: 17 cases of deficiency-cold syndrome and 15 cases of deficiency-heat syndrome. The result showed that in patients with deficiency-cold syndrome, the excretion of urine PGE2 was lower than that of the normal control (P less than 0.05), while the excretion of urine PGF2 alpha higher than that of the normal control (P less than 0.01) and hence the PGE2/PGF2 alpha ratio was much lower (P less than 0.01); in those with deficiency-heat syndrome, the excretion of urine PGE2 was higher (P less than 0.01), the excretion of urine PGF2 alpha had no significant change (P greater than 0.05) from the normal, and the PGE2/PGF2 alpha ratio was higher (P less than 0.01). The above result indicates a close relationship between prostaglandins and the cold and heat nature of syndromes in TCM. In connection with our previous studies that showed decreased functioning of the sympathetic-adrenomedullary system and/or increased functioning of the parasympathetic nervous system with diminished catecholamines and reduced cAMP/cGMP ratio in deficiency-cold syndrome while increased functioning of the sympathetic-adrenomedullary system with augmented catecholamines and cAMP in deficiency-heat syndrome, the change of prostaglandins level can be considered as an intermediate link in the pathogenesis of syndromes different in cold and heat nature. PMID- 2268917 TI - [Clinical and experimental study of shenshao tongguan pian in treating angina pectoris of coronary heart disease]. AB - Shenshao Tongguan Pian (SSTGP) is composed chiefly of saponins from the stem and leaf of Ginseng and Radix Paeoniae Alba, etc. The authors applied this remedy for the treatment of angina pectoris of CHD. From 1982-1988, the authors carried out a randomized double blind trial on altogether 565 cases of CHD divided into an experimental group to be treated with SSTGP and a control group treated with another TCM proprietory medicine, Dan Qi Pian, that had been used for many years clinically. The total effective rate of treating angina pectoris was 94.71% and ECG improvement rate 63.38% in experimental group whereas 66.99% and 23.38% respectively in the control group, the difference being very significant (P less than 0.01). Experiments with animals proved that SSTGP had more potent actions on CV system, such as dilatation of coronary arteries, promotion of coronary perfusion flow, lowering oxygen consumption of heart muscle, resisting the coronary spasm, anoxia and ischemia of heart muscle elicited by pituitrin, and prolongation of survival time of mice under anoxic state. In addition, laboratory examination also revealed SSTGP could promote the left ventricular output, lower the blood viscosity and inhibit the aggregation of blood platelets. Both acute and chronic toxicity tests showed SSTGP has no toxicity nor side effects. Therefore SSTGP is a new, safe and effective TCM proprietory remedy for CHD and angina pectoris. PMID- 2268918 TI - [Effect of ma-xin-shi-gan tang on the immune function in children with acute lower respiratory tract infection]. AB - This paper reported the effect of Ma-Xin-Shi-Gan tang (Decoction of Herba Ephedrae, Semen Armeniacae Amarum, Radix Glycyrrhizae and Gypsum Fibrosum) on the immune function of the children with acute lower respiratory tract infection (ALRTI). 64 cases of ALRTI children were chosen for clinical observation. Laboratory researches including 7 immune indexes: blood OKT3+ cell, OKT4+ cell, OKT8+ cell and OKT4+/OKT8+ cell ratio, serum IgG, IgA, IgM. Some tests in experimental mice were also made. The results showed: (1) Before treatment, the blood OKT3+ cell, OKT4+ cell and OKT4+/OKT8+ cell ratio of the ALRTI children were lower, OKT8+ cell was higher than that of the normal group, which indicated lowered function of cell mediated immunity (CMI) in ALRTI children. Furthermore, IgM content in serum of the ALRTI children was significantly higher than that of the normal group, which indicated a hyperhumoral immunity (HI). (2) Blood OKT4+ cell and OKT4+/OKT8+ cell ratio in children after treatment with the Decoction were higher than those before treatment, which suggested the Decoction can regulate the cell ratio of OKT4+ and OKT8+, and relieve the functional inhibition of CMI in ALRTI children, while comparing with the western medicine (WM) group, the blood OKT3+ cell, OKT4+ cell and serum IgG content in the Decoction group after treatment were higher. In the WM group, the serum IgG and IgA contents were lower than those of the normal group, which indicated inhibited function of HI after treatment. (3) In experimental mice, the Decoction can increase the phagocytic index of the macrophage, the spleen index and the level of serum hemolysin. It can also enhance the skin delayed allergic reaction of the mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268919 TI - [An approach to objective indexes for differentiating floating, sunken, feeble and forceful pulses in traditional Chinese medicine]. AB - Objectification of Pulse-taking diagnosis is very important for modernization of TCM. Nowadays radial sphygmogram at wrist is usually taken as an objective index of pulse condition, but there are no good means to differentiate quantitatively Floating, Sunken, Feeble and Forceful pulses. In the present paper sphygmograms were taken under a serious of counter-pressure (CP) in order to approach this problem. The CP was a pressure put on the transducer to imitate finger force during pulse-taking. At first the main wave of sphygmogram in all subjects was usually getting higher and higher as the CP increased. After a maximum amplitude was attended, on the contrary, it became lower gradually with further increase of CP. The sphygmogram with maximum amplitude was called optimum sphygmogram (OS) and its corresponding CP called optimum counter-pressure (OCP). Taking CP as abscissa and amplitude of main wave (A) as ordinate, a curve of relation between CP and A (CP-A curve) might be obtained. OCP in Floating pulse tended to low (5 10 kPa), and then the CP-A curve went downwards gradually following the increase of CP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268920 TI - [Tongue tip microcirculation in patients with different symptoms]. AB - Observations of tongue tip microcirculation were made on 104 patients with different symptom-complex [5 groups: Yin deficiency, Yang deficiency, Qi.blood deficiency, Qi stagnation-blood stasis, damp-heat] in view of TCM, and on 100 healthy persons. 10 indicators including the transverse diameter of the fungiform papillae, morphology of microvascular clumps in the tongue papillae, congestion of the top of microvascular loop, loop dilation, blood color, hemodynamics in microvascular loop, exudation, hemorrhage and loop morphology were observed. The results were: patients of each group were found to have to different degree microcirculation dysfunction; every group differed with Qi stagnation-blood stasis group of being most different. The numbers of abnormal indicators: Qi stagnation-blood stasis group had all 10; Yang deficiency group 9; Yin deficiency and Qi-blood deficiency group 8, 8 respectively; damp-heat group 7. This study discussed the relationship between tongue tip microcirculation of each group and the changes of tongue picture and typing of differentiation of symptoms and signs in view of TCM. PMID- 2268921 TI - [Protective action of Salvia miltiorrhiza aqueous extract on chemically induced acute myocardial ischemia in rats]. AB - Aqueous extract of Salvia miltiorrhiza (SM-H) can protect the acute myocardial ischemia and arrhythmia of Sprague-Dawley rats induced by isoproterenol (ISO) or BaCl2 with the following results: (1) intraperitoneal injection (i.p.) of SM-H for 3 to 5 days or intravenously (i.v.) just once significantly reduced the death rate of the animals, (2) i.v. SM-H pretreatment significantly increased the lethal dose of BaCl2 infusion, (3) i.p. SM-H significantly decreased premature ventricular contraction, ventricular fibrillation, bradycardia and mortality rate induced by bolus i.v. of BaCl2, and (4) i.p. SM-H also significantly reduced ECG J-point displacement of rats induced by ISO. PMID- 2268922 TI - [Effect of si jun zi tang on the macrophage cytotoxic activity in mice]. AB - The effect of Si Jun Zi Tang (SJZT) on the activities of peritoneal macrophage (M phi) mediated MTC and ADCC in normal and immunosuppressed mice were examined by isotope releasing assay (51Cr, 125I-UdR). The results showed the SJZT no significantly increased peritoneal M phi-mediated cytotoxic activity (MTC, ADCC) in normal mice. After the injection of immuno-depressive cyclophosphamide (Cy) alone (ip), the cytotoxic activities were decreased, but by treatment with Cy and SJZT, the cytotoxic activities were significantly increased compared with Cy group, the enhancing rates amounted to 74.40% (M phi-MTC) and 121.03% (M phi ADCC) respectively. It was demonstrated that the SJZT could protest against the effect that the Cy inhibited the activities of MTC and ADCC of peritoneal M phi in mice, but there was no significant effect on normal mice. It indicated that the function of SJZT's immunoregulation was related to the state of immune in body. PMID- 2268923 TI - [Clinical and experimental study of garlic in preventing and treating cardiovascular diseases]. PMID- 2268924 TI - [Pharmacological effects of fresh ginger and dried ginger]. PMID- 2268926 TI - [Therapeutic effects of anti-rheumatic tablet in ankylosing spondylitis]. AB - 188 patients of ankylosing spondylitis were treated with anti-rheumatic tablet compared with 30 patients with Indomethacin as control group. The results showed that spinal antiflexion and finger-ground test of both treated group and control group had improved significantly (P less than 0.05), but lateral curvature movement, thorax expansion test, 20 m walking time, and the levels of IgG, IgA, IgM, C3, ESR, CRP of the treated group had marked difference compared with those treated before (P less than 0.01). It was proved that in the treated group, the marked effective rate was 53.72%, while in the control group was 20.00%. There was significant difference between the two groups in effective rate (P less than 0.001). This revealed that anti-rheumatic tablet is a kind of ideal drug in treating ankylosing spondylitis. PMID- 2268925 TI - [Clinical study of soaked treatment of chronic osteomyelitis with herbal medicine]. AB - This paper represented 500 patients with chronic osteomyelitis who were treated with Chinese medicinal herbs, Gan-ling Immersion Formula, in which focuses were soaked in combination with other therapies from 1986-1989. Healing rate was 83.2%. Effective rate was 98.0%. This therapeutic method was more effective for treating chronic osteomyelitis of the hand and the foot with shorter course. It was also good for treating refractory skin ulcer and scar, ilium osteomyelitis and sclerosing osteomyelitis. This method was immediately effective for acute attack of chronic osteomyelitis. Fistula in half of the patients could be closed within two therapeutic course. Most of the non-union and delayed-union of the bones could be unionized as chronic osteomyelitis was healed. Most dead bones could remove spontaneously, some could be absorbable, and seldom should be removed by operating on. These herbs are easy to get. The method was so simple and so safe that it could provide a new way of treating chronic osteomyelitis. Experiments showed Gan-ling Immersion Formula possessed relative strong anti inflammation and external antibiotic effects. PMID- 2268927 TI - [503 cases of pallas pit viper bite with traditional Chinese medicine and Western medicine treatment]. AB - In this paper 503 cases of pallas pit viper bite had been treated with the method of TCM-WM. Among the 503 patients 491 were cured (curative rate 97.61%), however, 12 patients were unfruitful (unfruitful rate 2.39%). The results showed that the poisoning degree of these cases had a positive correlation with patient's age, distance of snake teeth prints in wound, duration before admission, local and systemic clinical manifestation, degree of secondary infection and the number of the organ and system affected. In the treatment of the pallas pit viper bite, it was considered that should insisting the excluding poison and detoxifying methods, so as to cut off the absorption of the poison into the body and promote the discharge of the poison from the body, protect and improve the hepatic and renal functions, keep the balance of inter-circumstance. Attach importance to prevent and treat secondary infection, and raise the awareness to prevent and treat respiratory failure. All these mentioned above were considered the key points to increase the curative rate of the patients. PMID- 2268929 TI - [Clinical and CT analysis of 35 cases of lumbar disc herniation before and after non-operative treatment]. AB - 35 cases of lumbar disc herniation were examined by clinical diagnosis and CT scanning. The results showed that there were 36 disc herniation (1 case of dual disc herniation). The radius vector of disc was 6.3 mm and the transverse diameter was 18.6 mm. There were 30 cases with sac of dura mater of spinal cord or nerve roots pressed and adhesive, yellow ligaments pachismus, lateral recessus filling and narrow bony lumbar vertebral canal. All patients were treated by means of manipulation. The clinical results showed that 29 cases (82.8%) had superior effects and 33 cases were effective. The clinical effective rate was 94.2%. CT re-scanning showed that disc reposition completely returned was 6 cases, and partially returned was 24 cases. The successful rate of the reposition by manipulation was 83.3%. The clinical analysis and CT showed that herniation of lumbar disc could be repositioned by means of manipulation. The reposition of herniation of disc was a key factor in clinical results but was by no means the only one. With regard to long duration of illness, repeated invasion, combined narrow bony lumbar vertebral canal, and non-improved central type herniation after a long period of treatment, the herniation of disc should be treated by operation. PMID- 2268928 TI - [Determination of blood flow of the lower leg in patients with diabetes mellitus and the effects of treatment with the principle of vitalizing blood and solubilizing thrombus]. AB - This paper reports the determination of blood flow of the lower leg in 50 cases of non-insulin dependent diabetes mellitus (NIDDM) using an XLJ-2 Bipolar Rheoencephalometry Impedance Rheogram. In patients with leg pain (but without obvious vascular pathological changes, 85 legs) the blood flow was decreased. In male patients the blood flow of the left leg (9 legs) was 3.28 +/- 0.47 ml/100ml.tissue.min (mean +/- S), while that in the right leg (11 legs) was 3.88 +/- 0.80; in females, the blood flow of the left leg (32 legs) was 2.72 +/- 0.8; while that in the right leg (33 legs) was 2.94 +/- 0.66. These figures were significantly (P less than 0.01-0.001) lower than those obtained from normals. In diabetic feet (15 painful legs) the decrease of blood flow of the lower leg was more apparent: it averaged 1.87 +/- 0.79 for the left leg (7 legs) and 2.66 +/- 0.87 for the right leg (5 legs) in male patients. The values were significantly different when compared with those of normals (P less than 0.001) or with those of the diabetic patients with leg pain (P less than 0.05). These results demonstrated that determination of the blood flow of the lower leg of diabetic patients might aid in early discovery of the abnormal changes of blood supply to the lower legs in diabetes mellitus and judge the degree of ischemia. Of the 50 cases of diabetics 32 were Qi-Yin deficiency with blood stasis while the remaining 18 cases were deficiency of both Yin and Yang with blood stasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268930 TI - [Effects of nifedipine and Paeonia lactiflora on plasma TXB2 and 6-Keto-PGF1 alpha in cholesterol-fed rabbits]. AB - The authors examined the influences of nifedipine and Paeonia lactiflora (PL) on plasma LPO, TXB2 and 6-keto-PGF1 alpha in cholesterol-fed rabbits. In this study, oral administration of nifedipine (15 mg/kg per day) and PL (0.5 g/kg per day) with 2% cholesterol diet for 15 weeks caused 60.75% and 74.24% reduction in the lesion area of aorta respectively. The levels of plasma LPO, TXB2, cholesterol, phospholipid and calcium of the intimalmedia of the aorta in the treated groups were significantly lower than those in the control group, but the level of 6-keto PGF1 alpha in the treated groups was significantly higher. The durations of TXB2 elevation and 6-keto-PGF1 alpha reduction were delayed. The ratio of TXB2/6-keto PGF1 alpha tended to balance. The ratio of TXB2/6-keto-PGF1 alpha was significantly positive correlation with the percentage of lesion area of the aorta. It is demonstrated that calcium metabolism plays an important role in thromboxane, prostaglandin, and LPO synthesis. In conclusion, the inhibition of LPO production and the regulation of TXA2-PGI2 balance may be one of the mechanisms of anti-atherogenesis of calcium antagonists and PL. PMID- 2268931 TI - [Comparison between the therapeutic effects of ginseng-aconitum-bupleurum injection and dexamethasone on septic shock complicated with disseminated intravascular coagulation induced by E. coli in dogs]. AB - In this paper, the authors report the therapeutic effects of Ginseng-Aconitum Bupleurum (GAB) injection on septic shock complicated with DIC induced by intravenous injection of live E. Coli in dogs. The experimental results indicated that the survival rate at 48 h after intravenous injection of live E. Coli was 30% in saline group, 80% in GAB, 90% in dexamethasone (Dex) group. The BPC, WBC, FG, AT-III, beta-GC, PHb were 82 +/- 28, 9.1 +/- 5.9, 1.85 +/- 0.41, 112 +/- 43, 0.37 +/- 0.17, 0.11 +/- 0.07 respectively for GAB, 70 +/- 37, 6.7 +/- 3.7, 1.55 +/- 0.36, 59 +/- 29, 0.91 +/- 0.28, 0.12 +/- 0.06 respectively for the saline group, 58 +/- 33, 6.3 +/- 2.9, 1.95 +/- 0.21, 103 +/- 43, 0.50 +/- 0.16, 0.13 +/- 0.06 respectively for Dex. The BPC, WBC, FG, AT-III levels of the GAB group were significantly higher than those in saline group and were not significantly difference from the Dex group. The beta-GC and PHb levels of the GAB group were significantly reductive than the saline group and were not significantly different from the Dex group. The results showed that the survival rate was higher, the DIC was inhibited and normal biomembranes were maintained in the GAB group. PMID- 2268932 TI - [Evaluation and clinical use of QRS scoring system for estimating myocardial infarct size]. PMID- 2268933 TI - [Quantitative Chinese pharmaceutical study on children pneumonia treated by Pu fu zhou]. AB - By method of quantitative Chinese pharmacy, the author studied the children pneumonia cases recorded in two books, "Pu Fuzhou's Medical Cases" and "Pu Fuzhou's Medical Experiences". The rule of Chinese medicine used by Pu Fuzhou was probed preliminarily. It was a characteristic that Pu Fuzhou treated the children pneumonia cases by using Pinelliae Tuber, Exocarpium Citri Rubrum, Jujube and Radix Glycyrrhizae. But the rate of using Herba Lophatherum was less in pneumonia group than in non-pneumonia (contrast) group. According to the rate of overdose prescriptions, 11 Chinese herbal medicines used frequently in pneumonia group were classified into 4 sections. Only overdosage rate of section B (Radix Glycyrrhizae and Peucedanum Decursivum Maxim) was correlated with various kinds of diseases. Referring to the compatibility of dosage of the two Chinese medicines used, there were positive correlation in 35 of 38 pairs, among them, P less than 0.05 in 20; negative correlation in 3 of 38 pairs, among them, P less than 0.05 in 1. It was revealed that in 18 of 38 pairs, in which no significant positive correlation was present, the dosages of Chinese medicine used by Dr. Pu varied with different degree of severity and kind of symptoms he treated. PMID- 2268934 TI - [Treatment and experimental study on activating blood circulation and removing blood stasis to cerebral hemorrhage during acute stage]. PMID- 2268935 TI - [Radiation sensitizing and protective action of Ligusticum wallichii Franch]. PMID- 2268936 TI - [Effect of Chinese medicinal herbs on sperm membrane of infertile male]. AB - The authors carried on the quantitative analysis of fluorescence polarization degree and fluorescent intensity on wheat germ agglutinin (WGA) receptor in sperm membrane surface and protein macromolecule 1-Anilinonaph thalene-8-suphonic acid salt (1,8-ANS) of sperm membrane to the patients with infertility and adult male with normal fertility, with the method of ultraviolet microspectrofluorometer (SMP, type: 05, made in West Germany). The results were as follows: the patient's WGA receptor in sperm membrane surface was decreased (P less than 0.001), and the 1, 8-ANS of fluorescent intensity in hydrophobic area of protein macromolecule of sperm membrane was increased (P less than 0.05). After the treatment of Shenjing Zhongzitang, WGA receptor was increased obviously and 1, 8-ANS of fluorescent intensity was changed to be almost normal. It showed that the Chinese medicinal herbs mentioned above have certain influence upon the constitution of WGA receptor and protein macromolecule of sperm membrane. PMID- 2268937 TI - [Regulatory effects of acupuncture and moxibustion on simple obese complicated with hypertension]. AB - Acupuncture and moxibustion is one of the important therapies in TCM for treating obese. The authors have treated 41 simple obese patients complicated with hypertension by acupuncture and moxibustion which obtained good results. In the treating group, a total effective rate was 87.8% (36 cases). For the purpose of understanding regulatory effect of acupuncture and moxibustion, the authors have observed the obesity indices, the lipid indices (TC, TG, VLDL-C, TC/HDL-C, HDL-C, LDL-C, LDL-C/HDL-C and AI), the physiological indices (saliva secretion, heart rate, respiratory rate, blood pressure and temperature) and the energy metabolism indices (BMR) in the simple obese complicated with hypertension before and after the acupuncture and moxibustion. The results showed that the therapeutic effect of acupuncture and moxibustion could have good results. At the same time, there were the benign regulatory effect of acupuncture and moxibustion in the overeating, the blood pressure, the vegetative nervous indexes, the lipid level and the energy metabolism. PMID- 2268938 TI - [Evaluation of therapeutic effects of acupuncture in treating ischemic cerebrovascular disease]. AB - In this article, the therapeutic effects of acupuncture and routine drugs in treating 20 cases of ischemic cerebrovascular disease, and in comparison with another 20 cases treated with sole routine drugs were studied. Effects of acupuncture were evaluated from the degree of functional nervous damage, EEG-map and somatosensory evoked potential. After treatment the results were as follows: the marks of functional nervous damage in the test group were reduced 13.0 average, but only 3.75 in the control group. There was a very remarkable difference between these two groups (P less than 0.001). Slow wave of the EEG-map in the test group were reduced 1.70 level average, but only 0.05 in the control group (P less than 0.001). theta wave of the EEG-map in the test group were reduced 1.05 level average, but only 0.25 level in the control group (P less than 0.001). The diversity of latent period of P45 peak wave value between left limbs and right limbs were reduced evidently in the test group and showed a very significant statistical difference. (P less than 0.05) as compared with the control group. The above results revealed that therapeutic effects of acupuncture were objective and were based on neurophysiological mechanism. PMID- 2268939 TI - [Use of xin bao in the treatment of 87 patients with sick sinus syndrome]. AB - Since 1987, the authors have observed the therapeutic effect of Xin Bao on 87 patients with sick sinus syndrome. Electrophysiological stimulation examination: SNRT greater than 1900 ms and CSNRT greater than 600 ms in all patients. Routine ECG and Holter monitoring ECG: (1) Persistent sinus bradycardia or/and atrio ventricular junction escape rhythms or/and premature beat, heart rate less than 48 +/- 6 beats/min in 40 patients; (2) sinus standstill (arrest) or secondary degree sinoatrial block in 10 patients; (3) bradycardia-tachycardia syndrome in 30 patients; (4) the heart rate greater than 60 beats/min in 7 patients. The major symptoms were dizziness, palpitation, chest press, malaise, remission in memory, nocturia, amaurosis and Adams-Stokes syndrome, etc. Self-comparison was taken, Xin Bao was given 2-10 tablets 2 or 3 times a day by oral administration for 2 months. The major symptoms of sick sinus syndrome was greatly improved after treatment. The total effective rate attaining to 85%. The improvement in heart function was also significant, the total effective rate being 80%. After treatment SNRT and CSNRT were shortened (P less than 0.01), the total heart beats for 24 hours and the average heart beats/min greatly increased (P less than 0.01). CO and EF increased too (P less than 0.05). No serious adverse reactions were found during the treatment. It was believed that Xin Bao could stimulate sino-atrial node and increase it's excitability. The basic heart rate was increased and the heart function improved with no adverse reactions. It may be administrated in long term. Therefore, Xin Bao may be recommended as appropriate drug for treating sick sinus syndrome. PMID- 2268940 TI - [Hyperlipidemia treated with xiaobu jianfei pian]. AB - A total of 51 cases with hyperlipidemia, who were defined deficiency symptom complex complicated by symptoms of excessiveness in TCM were studied clinically. The patients were divided into two groups at random. One group was treated with Xiaobu Jianfei Pian (XJP) as treated group, another with Fangfeng Tongsheng San as a control. It was found that XJP was able to lower total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) B significantly (P less than 0.001, 0.001, 0.001) while it had markedly improved clinical symptoms. It was also observed that XJP had good effects on the ratios of apoA1/B and TC/HDL-C, and was able to reduce body weight index. All of these were better than those of the control group statistically. These evidences indicate that XJP possesses clinical therapeutic effects on both lipid-lowering and lipid-adjusting, which suggest that XJP may be an effective anti hyperlipidemia medicine. PMID- 2268941 TI - [Immune function of cancer patients with spleen-deficiency syndrome]. AB - According to this study, the immunological function was aberrant in cancer patients with Spleen-deficiency syndrome. The TII cell in normal persons (n = 26) was 30, 86 +/- 9.70% (means +/- S) and in these cases (n = 43) was 22.62 +/- 9.92%, P less than 0.002. The cytotoxicity of NK cell in patients (n = 59) was 17.65 +/- 10.58%, in normal controls (n = 43) was 25.51 +/- 14.10%. The combining ability of NK cell in patients (n = 48) was 39.11 +/- 19.43%, the normal persons (n = 41) was 55.88 +/- 17.94%. It showed that the immune function of the cancer patients with Spleen-deficiency syndrome were markedly lower than that of normal persons. The serum IgA in saliva of patients (n = 37) was 0.44 +/- 0.17 microgram/ml. It was much higher than that of normals' (n = 24, 0.30 +/- 0.06 microgram/ml), P less than 0.001. Some patients' NK cell function and the level of level of SIgA in saliva were recovered to normal after treatment of Shengxue Tang which could strengthen the Spleen and replenish the Kidney. These studies proved that the TCM played an important role for modulating immune function in treating cancer patients. PMID- 2268942 TI - [Analysis on the traditional Chinese medicine syndromes of the patients with autoimmune thyroid diseases. Changes in the thyroid and immune functions in 109 cases]. AB - Eighty-nine cases of hyperthyroidism and 20 cases of hypothyroidism caused by Hashimoto's thyroiditis were observed in order to analyse the thyroid and immune functions of the patients, and their relationship with the syndromes of TCM. The results showed that, in the patients with Yin deficiency syndrome, the contents of total T4, T3 were higher than normal and TSH lower than normal, while in Yang deficient patients, the contents of total T4, T3 were lower than normal and TSH higher than normal. This results suggested that the states of thyroid functions were closely related to the TCM syndromes. It was also found that the percentage of OKT 4+ cells and the self-recognizing ability of lymphocytes were lower than normal in patients with hyperthyroidism and Yin deficiency. While in patients with hypothyroidism and Yang deficiency, they were higher than normal. These meant that the abilities of lymphocyte autoreaction in Yin deficient patients were in contrary tendency with those in Yang deficient patients. The former had the manifestation of over-inhibition while the latter, hyperaction. Besides, the contents of auto-antibodies were higher than normal in both the patients with hyperthyroidism and hypothyroidism, which manifested itself as a common character of autoimmune thyroid diseases. The results indicated that there were common characters as well as individual characters of thyroid and immune functions between hyperthyroid patients and hypothyroid patients, and these characters might well be the material bases of various syndromes in TCM. PMID- 2268943 TI - [Pre-, post-operation and before death of blood stasis syndrome in patients with gastric malignant tumor]. AB - In the past three years, the authors observed substance of tongue and 5 indexes of blood coagulation (AT-III, Fn, Fa, VIII R:Ag and beta TG) for a long time in 140 patients of gastric malignant tumor pre-operation, one month post-operation and 3 months before death. All patients were verified as gastric carcinoma by pathological section. The results showed that the positive rate of substance of tongue in patients pre-operation was as high as 58% (51/88), 5 indexes of blood coagulation in patients had obvious difference (P less than 0.001) comparing to that of healthy persons. This implied it existed relationship between gastric malignant tumor and blood stasis in TCM and accorded with diagnosis of blood stasis syndrome. With the resection of tumor focus, the states of blood stasis in patients had been improved to a certain extent. But the positive rate of substance of tongue post-operation was still as high as 51.1% (45/88) comparing to that pre-operation (P greater than 0.05), 5 indexes of blood coagulation in patients post-operation had no obvious improvement comparing to those pre operation. This showed that the simple resection did not basically improve blood stasis in patients. The another important result was that the substance of tongue and 5 indexes of blood coagulation of 23 patients in last 3 months before death had more obvious blood stasis comparing to those post-operation even those pre operation. This explained that blood stasis is one of the main characters of gastric malignant tumor before death. In conclusion, the extent of blood stasis syndrome can be used as an objective index to judge seriousness and prognosis of gastric malignant tumor patients' condition. PMID- 2268945 TI - [Anti-HBsAg herbs employing ELISA technique]. AB - With the aid of the ELISA system this schema represented a laboratory approach to the recognition of anti-HBsAg capability of herbs by using 300 herbal extracts. Altogether 10 herbs (3.0%) were identified as effective. When forming a multiplex plan by employing 10 average P/N ratios as exemplified by 5 varying doses of herb (0.3, 0.6, 1.2, 2.5, 5.0 mg/100 microliters), 2 varying concentrations of HBsAg (10.92, 14.26 P/N ratio), and 3 varying contact time periods (immediate, 1h, 2h) for the comprehensive appraisal of herb efficacy index, these 10 effective herbs were listed in the following order: Prunella vulgaris (1.00), Litchi chinensis (1.26), Gossypium herbaceum (1.45), Cudrania cochinochinensis (1.56), Caesalpinia sappan (1.73), Oldenlandia tenelliflora (1.77), Cautis parthenocissus (1.99), Evodia rutaecarpa (2.01), Portulaca grandiflora (2.44), and Anemone hupehensis (2.83). PMID- 2268944 TI - [Main pharmacological roles and clinical curative effect of sanbi rebao]. AB - Sanbi Rebao (contain 32 components, such as Radix Aconiti, Rhizoma Chuanxiong, Semen Strychni, Radix Glycyrrhizae, Radix Angelicae sinensis, Radix Ledebouriellae, Fructus Evodiae, borneolum syntheticum, etc.) had antagonistic action on the ear swollen response induced by croton oil and on the ear inflammation reaction caused by dimethylphenylene in mice. It could decrease significantly the response rate of turning its body induced by acetic acid, increase the pain threshold caused by warm, reduce the surface seepage of injure skin and accelerate the wound recovery. The above results showed Sanbi Rebao possessed the roles of dephlogisticate, analgesia and promoting wound recovery, Besides these, clinic research indicated that effective rate of Sanbi Rebao on pain or numbness caused by cold, damp and wind (rheumatism) was 97%. PMID- 2268946 TI - [Immunopharmacological effect of Cordyceps sinensis]. PMID- 2268947 TI - [Perioperative diagnostic pneumoperitoneum for unilateral inguinal hernias in children]. AB - Fifty-six pediatric patients (2.5 months-13 years old) presenting with unilateral inguinal hernia underwent intraoperative diagnostic pneumoperitoneum (Goldstein test) to evaluate the controlateral groin. Fourteen patients (25%) had positive results and underwent controlateral hernia repair. The positivity is found more frequent in females (37.5%) and in the left sided hernias (50%). The percentage of positive tests has found to be inversely proportional to the age of the patient which is 33% for children under 6 months of age and 18% over 24 months. It is also observed that none of the children with negative test admitted with the complaint of hernia within two years following the operation. Intraoperative diagnostic pneumoperitoneum is a rapid, safe and accurate means to evaluate the contralateral groin in children presenting with a unilateral inguinal hernia. The test eliminates the high negative exploration rate and possible injury to cord structures with routine bilateral exploration. PMID- 2268948 TI - [Congenital cutaneous aplasia of the scalp. Apropos of 4 cases]. AB - Report of four cases of congenital defects of the scalp. In two of these cases, the skin defect was associated with a skull defect and in one, there were other cranial deformities. In each case, the lesion seemed isolated in otherwise normal children. This study contains a review of congenital scalp defects. The different aspects of this rare disease are presented and the treatment is discussed with reference to natural evolution. The authors differentiate between cases with isolated lesion and cases with associated malformations or abnormalities, malformation syndromes, as has been previously defined. In the case of skull defects, it is thought that immediate reparatory surgery must be performed, to prevent infection and hemorrhage of sagittal venous sinus, as it was the case in one of the four children. The covering of the defect can be realized with rotated skin flaps, which seem preferable to any form of plastic surgery, for cosmetic reasons, and for the secondary treatment of the skull defect, if this is necessary. When spontaneous closure of the bone defect, is not noted, which occurs generally in the case of large defects, it seems reasonable to close the latter by cranio-plasty, to protect the brain. In one of the four cases reported, this technical approach of the lesion was used, with a good result being reported, four years later. PMID- 2268949 TI - [Epiphyseal fractures-dislocations of the lower extremity of the tibia]. AB - Ninety six distal tibial epiphyseal fractures were identified and treated in our institution from 1976 to 1988. The average age was twelve years and eight months (range two to seventeen years), but seventy-one were between eleven and fourteen years old. Using the Salter-Harris classification we have found twelve type 1 tibial fractures, fourty-two type 2, thirty type 3 and twelve type 4. Four were triplane fractures and seven were Tillaux fractures. Twenty-six had injuries in the medial corner of the ankle mortise (Mac-Farland). Fifty patients were treated non-operatively with closed reduction and plaster cast. Fourty-six fractures were treated surgically. Seventy patients were available for follow-up evaluation. The average follow-up was thirty-two months (range 6 months to eleven years). The tibial distal epiphyseal cartilage was closed in 48 patients. As short-term complications we have seen three post-operative displacements after closed reduction; all of them were treated surgically. Five incomplete closed reduction needed open reduction needed open reduction and bone fixation. Two infections occurred after a surgical approach. Among late complications we have seen eleven premature epiphyseal cartilage closure (rate 15%). Four were responsible of angular deformities. One child has a tibial osteotomy for varus deformity after a medial closure. Two ankle arthritis occurred: one of them was seen after a post operative infection. In two cases of fracture of the medial mortise corner, a valgus deformity with hypertrophy of the medial malleolus occurred. Ankle arthritis is the most severe complication of the adolescent articular fractures (Tillaux and triplane fractures).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268950 TI - [Ambulatory management of idiopathic scoliosis using the Lyon orthopedic treatment. 70 cases reviewed]. AB - This work tries to clarify the place which is due to the modified Lyons orthopaedic treatment of scolioses. Actually, nowadays, because of progress in surgery, some people abandon all orthopaedic treatment which caught severe progressive scolioses at the end of the growth period. The study covers 70 patients from a minimum distance of 3 years after the end of orthopaedic treatment. The treatment, in comparison with the classical Lyons treatment has two principle modifications: sequence protocol plaster then corset, purely external, not necessitizing hospitalisation or a stay in a specialised centre; and the use of resine which lightens the plaster. The results are given in angular loss as regards to the end of treatment, according to 3 factors; chronological form of the scoliosis, localization of the scoliosis, degree of the initial curvature. It emerges that in spite of the absence of hospitalisation at the beginning of the treatment, the results are comparable to those in literature (8, 19). We obtained 39 stabilizations of progression, 8 moderate aggravations without ulterior surgery, that is 67% good results. Our study confirms the high failure rate of orthopedic treatment of initial scolioses of 50 degrees and more (50%); compared to initial scolioses of 49 degrees to 20 degrees (29%); of dorsal scolioses (42%) compared to lumbar scolioses (18%); of child scolioses (40%) compared to adolescent scolioses (17%). It leads us to keep the Lyons treatment for progressive scolioses of 25 degrees to 40 degrees, from the start of puberty, or as preparation for surgical treatment. PMID- 2268952 TI - [Dysphagia disclosing a cervical disk calcification in a child. Apropos of a case and review of the literature]. AB - Intervertebral space calcification (ISC) is infrequent, it involves different levels of the spine. Anterior prolapse of the calcification at cervical level may get dysphagia, exceptional and transitory sign of the disease. "Crisis" of pain is a criteria of removing of calcification existing long time before its detection. PMID- 2268951 TI - [Paraganglioma of the carotid body. Apropos of a case in a 14-year-old child]. AB - Carotid body tumors are encountered infrequently. We report a case of a fourteen year old boy presenting an inflammatory biologic syndrome with a right neck mass. The diagnosis was first an Hodgkin disease but the surgical approach and histological examination of the neck mass conclude to a benign carotid body tumor. A subadventitial excision allowed a complete recovery with one year follow up. The diagnosis of these tumors is essentially made by arteriography. They are benign in most of the cases but sometimes need for a vascular reconstructive surgery in very extended forms. PMID- 2268953 TI - [Post-traumatic spinal arachnoid cyst]. AB - A 15 year old boy presents two fractures of the left inferior member (femur and tibia), after a motor-cycle accident. An osteosynthesis by plate and screws was performed, in emergency. In immediate post-operative days, a radicular paresia of the left inferior member appear especially on exterior popliteus sciatic nerve. The electromyogram confirm the diagnosis. However, these is nor pain nor fracture of the sacro-lumbar spine. The consolidation of femur and tibia fractures is normal. The neurologic recuperation is slow but progressive. A year after the accident, because the recuperation is not complete, an MRI is performed. An arachnoidal cyst surrounding the L5 and S1 roots is diagnosed. The surgery is decided. The ablation of the cyst is performed in the same operative time that the ablation of plate. The histology of the paries of the cyst confirm, by hemosiderimic deposits, the traumatic etiology. The arachnoidal cyst is rare, particularly in the childhood. It is always difficult to know the relation between the cyst and the symptom. It is also impossible to be certain of traumatic etiology: traumatic cyst or traumatised cyst? The surgical indication is lawful by the existence of clinical signs, because 50 per cent of cases are improved or recovered. PMID- 2268954 TI - [Sacrococcygeal teratoma. Apropos of 15 cases]. AB - Fifteen cases of sacrococcygeals teratomas were treated at our hospital over the last ten years. There is no correlation between prematuration and tumor weight, as between tumor weight and low babys' weight. High tumoral weight didn't influence the prognosis. The treatment is always surgical. Chemotherapy was used only for recurrence in one case (the patient is dead). For all the cases, we performed a perineal procedure without abdominal procedure. No patient had an abdominal extension of the teratoma. PMID- 2268955 TI - [Extrahepatic biliary tract atresia and a common biliopancreatic canal. Review of the literature apropos of a case]. AB - The authors report the case of an 3 months old caucasian boy which had an extrahepatic biliary atresia associate with a congenital biliary cyst and an anomalous pancreaticobiliary junction. The patency between gallbladder and duodenum permits the operative opacification of this long common pancreaticobiliary channel. The congenital biliary cyst was located on the upper part of the common bile duct and was obstructed by biliary concretions. Unfortunately, no patency between intrahepatic bile ducts and this cyst was found. Because this long common pancreaticobiliary channel may cause biliary dilatation or biliary cancer, we performed an hepatic portoenterostomy rather an hepatic portocholecystostomy. A few weeks later, the bile flow was restored and the jaundice decreased. With a follow up of 18 months, this boy is currently anicteric, despite the hepatic fibrosis found on the operative biopsy. The association extrahepatic biliary atresia-long common pancreaticobiliary channel is uncommon and only 20 cases were reported. In our case, the pancreatic juice reflux into the biliary tract might have caused the dilatation of the common bile duct and the biliary atresia by chronic obstructive cholangiopathy. PMID- 2268956 TI - [Neonatal pyloric obstruction. Diagnostic and therapeutic aspects. Apropos of 5 cases]. AB - Five cases pyloric obstruction, revelated at the birth-period were summarized from 1964 to 1987; 1 pyloro-duodenal atresia, two cases of total pyloric obstruction by diaphragm, two cases of pyloric obstruction associated with several ileal and/or-colic atresia in the same family, and suspected at the antenatal echographic study. The treatment was either pyloro-duodenal anastomosis (1 case) or diaphragmatic resection with pyloroplasty (4 cases). In immediate results are obtained one immediate death, at the third day, and 4 initial good results; but two deaths came in a further period at 3 months and 8 months (the same family) with sepsis after ileus. A syndrome of immuno-deficiency was demonstrated in this two familial cases. PMID- 2268957 TI - [Uretero-calicostomy for hydronephrosis caused by junction disease in children and adolescents. Apropos of 35 cases]. AB - 35 children and adolescents were submitted to ureterocalicostomy for PUJ obstruction. The surgical procedure is explained and specially the importance of performing a regular, muco-mucosal anastomosis to avoid its secondary stenosis. 9 patients have an excellent result with absence of clinical symptoms, sterile urinalysis and normal IVP. 20 patients have a good result with absence of clinical symptoms, sterile urinalysis and improvement of the dilatation of the cavities. 2 secondary nephrectomies have had to be performed because of a dysplastic kidney (1 patient) or of a parenchymal infection (1 patient). 2 patients have no clinical symptoms but have no improvement of their IVP. 3 kinds of indications have been distinguished: failures of previous surgery of the PUJ (5 patients); PUJ obstruction associated with congenital kidney abnormalities as horseshoe kidney (15 patients) and malrotation (3 patients); severe PUJ obstructions with a very thin parenchyma (12 patients). Ureterocalicostomy appears to be a helpful procedure in some defined situations where a declive drainage of the urine essential. No late deteriorations have been recorded in this series. PMID- 2268958 TI - [Posterior vertical lumbotomy in pediatric practice. Apropos of a series of 294 cases]. AB - The study involves 294 cases. Essentials indications of posterior approach were for pelvic stones or lumbar ureteral stones 198 cases. Theres used this approach for abnormalities in the uretero-pelvic-jun (32 cases) and some staghorn srones (24 cases). The lateral posterior vertical lumbotomy passesses the advantage over classical lateral lumbotomy of being less disturbing to muscle, being less painful postoperatively stay. PMID- 2268959 TI - [Congenital vesicovaginal fistula. Commentary and review of the literature apropos of a case]. AB - A case of urinary incontinence through vesico vaginal fistula is related in a five year old girl. Its congenital origin is probable. The right ureteral orifice joins up with the fistula, in full duct. The corresponding kidney is hypotrophic and subjected to the vesico renal flow of the third degree. The incontinence disappears immediately. The literary studies have been analysed. Few are really vesico vaginal fistulas and few have a congenital origin. PMID- 2268960 TI - Uric acid nephropathy: management pearls. PMID- 2268961 TI - Differential diagnosis of hypersensitivity vasculitis. PMID- 2268962 TI - Intra-arterial chemotherapy for brain tumors. AB - Direct comparisons of theoretical modeling with actual drug delivery can lead to improved brain tumor therapy. In this study, normal and brain tumor-bearing rabbits received infusions of BCNU, or carmustine (1,3-bis [2-chlorethyl]-1 nitrosourea), with ethanol or hyperoxygenated perfluorocarbons as BCNU diluent. When ethanol was used as a diluent, right (infused) hemisphere:left (noninfused) hemisphere ratios of BCNU concentrations in both rabbit groups were markedly lower than had been predicted with theoretical pharmacokinetic modeling. When perfluorocarbons were used as a diluent, ratios of BCNU were significantly improved. These laboratory studies were directly translated into a two-phase protocol for human brain tumor patients. This combined research program demonstrates the successful integration of laboratory and clinical programs. PMID- 2268963 TI - Evaluation and treatment of generalized pruritus. AB - Generalized pruritus may be symptomatic of dermatologic disease or it can be a manifestation of a systemic disorder. When the cause of generalized pruritus is not immediately evident, careful clinical and laboratory evaluation and close follow-up are needed to ensure appropriate diagnosis and treatment. PMID- 2268964 TI - Stasis ulcer treatment with compression dressing. AB - A compression dressing system is an easily learned and effective alternative to the Unna boot for treatment of venous stasis ulcer. The treatment is well accepted by patients and appears to have efficacy comparable to that achieved with the boot, but without the problems associated with the boot, such as maceration, poor fit, and inability to observe and bathe the skin. PMID- 2268965 TI - Assessment of the size of acute myocardial infarction. I: Biochemical methods. AB - Determination of infarction size is essential to evaluate interventions designed to salvage myocardium. Properly executed enzyme methods probably have the highest accuracy but can only be used in the early stage of infarction. Measurement of slowly catabolized enzymes such as LDH, LDH-1, and alpha-HBDH is recommended for routine purposes. PMID- 2268966 TI - Assessment of the size of acute myocardial infarction. II: Electrocardiography and imaging methods. AB - The electrocardiogram gives a reasonable estimate of infarct size but the confidence limits are wide, and the estimates are unreliable in inferior wall infarction. Infarct size also can be determined from perfusion scintigraphy, assessment of left ventricular dimensions, wall motion disturbances, and other characteristics of the left ventricular wall. Nuclear magnetic resonance imaging, particularly with contrast enhancement, has the greatest potential for accuracy. PMID- 2268967 TI - Diagnosis and management of infective endocarditis. AB - Advances in chemotherapy and surgery have significantly improved the outcome of infective endocarditis, but the disease remains a therapeutic challenge with an overall mortality of 20%. More cases of infective endocarditis seen today are associated with prosthetic heart valves, intravenous drug abuse, or complications of medical and surgical technology. Prosthetic valve endocarditis occurs in 1% to 4% of patients with prosthetic valves. Echocardiography is not a precise diagnostic test for endocarditis, but it helps detect a variety of cardiac lesions, including valvular incompetence, annular ring abscesses, and sometimes vegetations. Serum bactericidal titers are predictive of neither cure nor treatment failure. The principal indication for urgent surgical intervention is acute valvular dysfunction. Other considerations for surgery include evidence of myocardial invasion, infection by antibiotic-resistant organisms, and large vegetations. For patients at risk of infective endocarditis, antibiotic prophylaxis during invasive procedures is an accepted practice. PMID- 2268968 TI - Pancreas transplantation: state of the art. AB - Improvements in technique and in the diagnosis of rejection have led to progressively better pancreas transplant graft and patient survival rates over the past 5 years. Refinements in organ preservation are making it easier for centers to share organs, with better immunologic matching and therefore additional improvement in results. As new immunosuppressive agents become available, pancreas transplantation may be an option for diabetic patients early in the course of their disease, before secondary complications become disabling. PMID- 2268969 TI - Monocytic leukemoid reaction, glucocorticoid therapy, and myelodysplastic syndrome. AB - A leukemoid reaction is a complex and poorly understood response by the bone marrow to a variety of stresses; although any peripheral blood cell line may be involved, it is rarely a purely monocytic event. A case is reported of a true monocytic leukemoid reaction in a patient with myelodysplastic syndrome related to the effect of corticosteroids on the underlying marrow disorder. PMID- 2268970 TI - Myelodysplastic syndrome and transient acantholytic dermatosis. AB - Focal acantholytic dyskeratosis consistent with the clinical and histological features of Darier's type of transient acantholytic dermatosis occurred in a man with myelodysplasia. Topical steroids and systemic antihistamines provided temporary and moderate relief from pruritus, but failed to control the dermatosis. PMID- 2268972 TI - Autosomal dominant osteopetrosis type II with "malignant" presentation: further support for heterogeneity? AB - The osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a "benign" prognosis, in contrast to the "malignant" course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis. PMID- 2268971 TI - Possible association of rare autosomal folate sensitive fragile sites and idiopathic mental retardation: a blind controlled population study. AB - The expression of folate sensitive fragile sites (FS) was assessed in cord blood lymphocyte cultures obtained from 790 newborns (NB) and in peripheral blood lymphocyte cultures from 326 institutionalized mentally retarded residents (MR). The mean rate of expression of common FS and the occurrence of rare FS was significantly higher in the MR population. Age, sex and history of chronic medication use did not appear to influence common FS expression in the MR population, 3/790 (0.38%) NB and 5/326 (1.53%) MR exhibited rare autosomal folate sensitive FS, a 4-fold difference in incidence (P = 0.009, Poisson test). Four of the five MR who expressed rare FS were considered to have idiopathic MR (4/179 or 2.2%). The occurrence of rare FS in 1/147 (0.68%) MR with known etiology is not significantly different from the frequency of occurrence in the NB population (P = 0.428, Poisson test). In this population, rare FS appear to be overrepresented in the idiopathic etiology MR group. PMID- 2268973 TI - Association of hypercholesterolemia and apolipoprotein E4 in school children. AB - To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school-age children with hypercholesterolemia and of 51 age, sex and obesity index-matched controls with normocholesterolemia by two-dimensional gel electrophoresis APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p less than 0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children. PMID- 2268974 TI - Phenylalanine hydroxylase gene: silent mutation uncovers evolutionary origin of different alleles. AB - Analyzing a panel of 94 phenylketonuria (PKU) alleles for mutations within the phenylalanine hydroxylase (PAH) gene, we identified a G to A transition in exon 7 corresponding to nucleotide 957 in the cDNA sequence. This nucleotide substitution generates a new Alu I site (...GTGGCT...----...GTAGCT...), but does not change the encoded amino acid (GTG245----GTA245 = VAL). In our panel of patients the Alu I polymorphism is exclusively associated with haplotypes 4 (mutant or normal alleles) and 3, 16, 17, 28 (normal alleles). PMID- 2268975 TI - Reproductive planning after genetic counselling: a perspective from the last decade. AB - Studies from the last decade on factors influencing reproductive planning after genetic counselling were reviewed. Increased possibilities of DNA-analysis and prenatal diagnosis might have brought about a shift in the paramountcy of factors influencing reproductive planning after genetic counselling. In contrast to the literature in the seventies, the magnitude of the genetic risk was no longer found to be one of the decisive factors in postcounselling reproductive planning. Instead, the interpretation of the risk as high or low and the desire to have children appeared to be paramount. The impact of new developments in DNA-analysis in prenatal diagnosis and presymptomatic testing will be an important subject for future studies on factors influencing reproductive planning. PMID- 2268976 TI - The wrinkly skin syndrome: a report of a case and review of the literature. AB - A 2 1/2-year-old boy born of Jewish Moroccan parents is reported with physical findings of wrinkled skin on the dorsum of the hands and feet, with poor skin elasticity, syndactyly, mild kyphosis and poor muscle tone, the diagnosis being the wrinkly skin syndrome. All reported cases of this heritable disorder of connective tissue are reviewed and discussed in terms of genetics, ethnic clustering and differential diagnosis. PMID- 2268977 TI - Interstitial deletion of the short arm of chromosome 4 in a boy with mild psychomotor retardation and dysmorphism. AB - A 17-month-old boy is reported with 46,XY,del(4) (p15.2p15.32). He had mild psychomotor retardation and multiple minor anomalies, without growth retardation or microcephaly, which differs from the classical 4p--syndrome (Wolf-Hirschhorn syndrome). The activity of dihydropteridine reductase, a genetic marker for chromosome 4p15.3, was half that in a normal control. PMID- 2268978 TI - "Isolated" radial ray defect may be due to Rothmund-Thomson syndrome. PMID- 2268979 TI - Interstitial cellular infiltration detected by fine-needle aspiration biopsy in nephritis. AB - Fine-needle aspiration biopsy (FNAB) was used to detect renal mononuclear interstitial inflammation in 56 patients with various types of nephritis (20 IgA nephropathy, 8 focal necrotizing glomerulonephritis, 7 interstitial nephritis, 6 non-classifiable chronic glomerulonephritis, 5 mesangial proliferative (non-IgA) chronic glomerulonephritis, 4 focal glomerulosclerosis, 6 normal histology, who were examined for microscopic hematuria, and 7 controls). Regular renal biopsies for histological and immunofluorescence studies were simultaneously obtained, and available for comparative analysis (not controls). Differential counts of mononuclear infiltration and subtyping of T-cell infiltration into T-helper (T-h) and T-suppressor-cytotoxic (T-s-c) cells, as detected by immunoperoxidase stains from FNAB, were correlated to clinical manifestations and renal function tests. Generally, our results indicated increased mononuclear cell infiltration (monocytes, lymphocytes, and/or activated lymphocytes) in FNAB of patients with IgA nephropathy, interstitial nephritis or focal necrotizing glomerulonephritis (especially monocytes in IgA nephropathy and interstitial nephritis, p less than 0.05 compared with controls, lymphocytes in focal necrotizing glomerulonephritis, and non-classifiable glomerulonephritis, p less than 0.02 and 0.05, respectively). The number of infiltrating activated lymphocytes was significantly increased in focal necrotizing glomerulonephritis, interstitial nephritis and focal glomerulosclerosis, p less than 0.05, less than 0.01 and less than 0.01, respectively. FNAB was at least as sensitive as histological examination for the quantification of interstitial cellular infiltration, and it allowed for cytological differential counts. Patients had decreased T-h and increased T-s-c cell counts, which were accentuated in FNAB compared with peripheral blood, although there were strong positive correlations between local and peripheral counts (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2268980 TI - Use of aminohydroxypropylidene bisphosphonate (AHPrBP, "APD") for the treatment of hypercalcemia in patients with renal impairment. AB - Aminohydroxypropylidene bisphosphonate (AHPrBP, "APD") is a relatively new bisphosphonate which has been shown to be effective for control of hypercalcemia due to a variety of causes. Renal impairment has been reported following the use of other bisphosphonates and pre-existing renal impairment has been regarded as a contraindication to the use of AHPrBP. We report the successful use of intravenous AHPrBP to control hypercalcemia in three patients with renal impairment, one of whom was dialysis-dependent. No significant side effects were noted; in particular, there was no further deterioration in renal function. Intravenous AHPrBP may be a safe and effective agent for the control of hypercalcemia in patients with renal impairment. PMID- 2268981 TI - Secondary effects of erythropoietin treatment on metabolism and dialysis efficiency in stable hemodialysis patients. AB - To test the possible effect of erythropoietin (EPO) induced higher hematocrit on dialysis efficacy and metabolism, 14 metabolically stable hemodialysis patients were evaluated with various kinetic methods, including total dialysate collection. Tests were performed twice before EPO treatment and twice when hemoglobin had stabilized in the targeted range. Samples were frozen and batch analyzed for each patient after completion of the study. During this period, dialysis regimens were fixed. EPO treatment caused several significant changes. Hematocrit increased from 21.5% to 34.3%. Pre- and postdialysis serum potassium increased 0.3-0.4 mmol/l, and 56% more potassium binder was given. Serum phosphate concentrations were unchanged, but the aluminum hydroxide dose had been raised 44%. Dialyzer clearance decreased for urea (4.8%), creatinine (14.7%), phosphate (16.5%) and potassium (8.6%). The ratio of postdialysis/predialysis measurements changed for calcium, creatinine and uric acid. Five patients experienced enhanced appetite, but average dry weight did not change, nor could changes be demonstrated for protein catabolism, generation rate of urea and creatinine, or their distribution volumes. Estimated sodium intake remained unchanged. The findings indicate that EPO treatment reduces dialysis efficiency slightly for a number of substances, but in the metabolically stable patient there are no impressive dietary changes. Problems can be overcome by appropriate changes of dialysis regimen and medication. PMID- 2268982 TI - Comment on "Treatment of resistant CAPD peritonitis by temporary discontinuation of peritoneal dialysis" by Cairns et al. PMID- 2268983 TI - Early and recurrent venous graft thrombosis after kidney transplantation: benefit of an early surgery. PMID- 2268984 TI - Thrombotic microangiopathy with reversible acute renal failure in a cardiac transplant recipient under cyclosporin. PMID- 2268985 TI - Therapeutic drug monitoring of phenytoin. Rationale and current status. PMID- 2268988 TI - Influence of age on the pharmacokinetics of alfentanil. Gender dependence. AB - Studies on the effects of age on the pharmacokinetics of alfentanil are inconclusive. A possible factor in explaining the differences between various studies could be the effect of gender. The authors studied the effects of age on the pharmacokinetics of alfentanil in female (n = 21) and male (n = 15) patients undergoing lower abdominal surgery under nitrous oxide alfentanil anaesthesia. There was a significant negative correlation (r = -0.79, p less than 0.001) between plasma alfentanil clearance (CL) and age in women (less than 50y, median CL 24.84 L/h; greater than 50y, median CL 14.52 L/h), but not in men (less than 50y, median CL 19.44 L/h; greater than 50y, median CL 16.2 L/h). The conclusion is drawn that the effects of age on the pharmacokinetics of alfentanil are gender dependent. PMID- 2268990 TI - Adult respiratory distress syndrome. PMID- 2268989 TI - The adult respiratory distress syndrome. Definition and prognosis. AB - This article provides an expanded definition of acute lung injury and the adult respiratory distress syndrome and describes the value of using this definition for establishing prognosis by discussing the basis for the acute lung injury scoring system, the various clinical disorders that may be associated with acute lung injury and how they affect outcome, and the influence of nonpulmonary organ failure on the outcome of patients with acute lung injury. PMID- 2268991 TI - Multiple organ failure. AB - Diagnostic criteria for individual organ system failure are imprecise, a factor that adds a considerable amount of ambiguity to this area of clinical research. Nonetheless, multiple organ failure is a common sequela of ARDS and other catastrophic medical and surgical illnesses that continues to limit patient survival. The cumulative weight of investigative evidence currently supports the premise that concepts of acute respiratory failure must encompass the abnormal gas exchange in the systemic as well as the pulmonary microvasculature. In this context, we need not dispense with the term ARDS, as respiratory distress applies equally to the nonpulmonary organs as well as the lungs. PMID- 2268992 TI - Pulmonary pathology of the adult respiratory distress syndrome. AB - Lung morphology in ARDS reflects the rapid evolution from interstitial and alveolar edema to end-stage fibrosis consequent to injury of the alveolocapillary unit. This morphologic progression, termed diffuse alveolar damage, has been subdivided into sequentially occurring exudative, proliferative, and fibrotic phases. Pulmonary lesions correlate with the phase of alveolar damage rather than with its specific cause. As suggested by experimental models of acute lung injury, the pathologic features seen in humans are consistent with the effects of a host of injurious stimuli and the complex interaction of inflammatory mediators on alveolar epithelial and capillary endothelial cells. Although ARDS frequently culminates in "interstitial" fibrosis, the organization of intraluminal exudate dominates the histologic picture in the proliferative phase and establishes the framework for subsequent fibrous remodeling of the lung. Involvement of the pulmonary vasculature is an important aspect of ARDS, from the initial phase of edema to the terminal stage of intractable pulmonary hypertension. Vascular lesions include thrombotic, fibroproliferative, and obliterative changes, which, like the parenchymal lesions, correlate with the temporal phase of diffuse alveolar damage. Although ARDS is characterized by extensive bilateral lung involvement, alveolar damage can affect the lung in a localized fashion. "Regional alveolar damage" is associated with the same clinical risk factors as diffuse damage, suggesting that there is a spectrum in the extent of lung involvement and disease severity in patients at risk for ARDS. The factors that govern which patients will develop the fulminant syndrome are poorly understood. It must be re-emphasized that the lung is stereotyped in its response to injury, and, consequently, descriptive, or even quantitative, studies of lung morphology can only provide clues regarding the initiating factors and pathogenetic mechanisms of ARDS. Progress in understanding the pathogenesis of ARDS and the devising of rational approaches to therapy will ultimately depend on careful clinical and experimental studies that unravel basic mechanisms of cellular injury and response. The course of these investigations must be guided by and constantly correlated with the pathologic features that occur in humans. PMID- 2268987 TI - Pharmacokinetic drug interactions with cyclosporin (Part II). AB - Part I of this article, which appeared in the previous issue of the Journal, considered the potential mechanisms of drug interactions with cyclosporin, and divided the interacting drugs into 2 categories. Drugs that decrease cyclosporin concentrations (e.g. anti-convulsants, rifampicin, etc.) were dealt with first; the authors then moved on to consider the second category, those that increase cyclosporin concentration (macrolide antibiotics, azole antifungal drugs). Part II continues the survey of this category. PMID- 2268986 TI - Hepatic drug metabolism and aging. AB - Although there is considerable variation in the effect of age on drug biotransformation, the metabolism of many drugs is impaired in the elderly. Age related physiological changes, such as a reduction in liver mass, hepatic metabolising enzyme activity, liver blood flow and alterations in plasma drug binding may account for the decreased elimination of some metabolised drugs in the elderly. It is difficult, however, to separate an effect of aging from a background of marked variation in the rate of metabolism due to factors such as individual metabolic phenotype, environmental influences, concomitant disease states and drug intake. The prevailing data suggest that initial doses of metabolised drugs should be reduced in older patients and then modified according to the clinical response. In most studies the elderly appear as responsive as young individuals to the effects of compounds which induce or inhibit the activity of cytochrome P450 isozymes. Concurrent use of other agents, which induce or inhibit drug metabolism, mandates dose adjustment as in younger patients. Many questions remain unanswered. For instance, limitations of in vitro studies prevent any firm conclusion about changes in hepatic drug metabolising enzyme activity in the elderly. With aging, some pathways of drug metabolism may be selectively affected, but this has not been adequately scrutinised. The possibility that metabolism of stereoisomers may be altered in the elderly has not been adequately tested. The effect of aging on the distribution of polymorphic drug metabolism phenotypes is still not established, despite potential implications for disease susceptibility and survival advantage. PMID- 2268993 TI - Mechanisms and mediators of the adult respiratory distress syndrome. AB - In 1990, we are much less certain that we understand ARDS than we were in 1982, and we have yet to identify specific therapy. It is tempting to conclude that we have made no progress, but this conclusion would be unwarranted. In those 8 years, important advances have been made. The complement hypothesis has survived, with significant modifications. Recognition of the importance of infection in clinical outcome and of endotoxin in augmentation of neutrophil-mediated injury has evolved in concert and meshes well. A new class of peptide mediators, cytokines, has assumed a central role. Lipid mediators now appear as modulators of cytokine-induced effects by priming, amplification, and regulation of gene expression rather than as unifactorial "causes" of the physiologic manifestations of ARDS. These interdigitating mechanisms have been recognized as pansystemic, resulting in overt multiple organ dysfunction and ultimately in death if amplification mechanisms go unchecked. Technologies in molecular genetics, generally unknown to the pulmonary community in 1982, have had a significant impact. Recombinant cDNA technology has permitted identification of the existence, structure, and functions of novel cytokines; made them available in sufficient quantity for detailed study; and prompted interest in the regulation of gene expression in the evolution and resolution of inflammation. Proteins modified by genetic engineering, as well as monoclonal antibodies and receptor antagonists for specific cytokines, are promising future approaches to therapy. At present, the complexity of the redundant networks by which inflammation is regulated seems bewildering in relation to ARDS. Bewildering or not, the age of the "mediator" of ARDS, and of the corresponding therapeutic "magic bullet," is over. The complexity of the system of regulatory checks and balances must be addressed at the molecular level. PMID- 2268994 TI - Sepsis syndrome, the adult respiratory distress syndrome, and nosocomial pneumonia. A common clinical sequence. AB - Systemic sepsis and pneumonia are common predisposing factors for ARDS, which can serve as the initial manifestation of the multisystem organ failure syndrome. Primary pneumonia that necessitates ICU admission leads to ARDS in approximately 10% of patients. Systemic infection can also lead to ARDS, but when bacteremia alone is present, the risk is low (probably less than 5%). If the septic syndrome with a hemodynamic and end-organ response develops, the ARDS may follow in as many as 40% of patients. When multiple risk factors for acute lung injury are present, the risk of developing ARDS rises dramatically. The septic syndrome, acute lung injury, and multiorgan failure are closely tied to one another because bacterial cell walls can activate inflammatory mediators, such as interleukin-1 and tumor necrosis factor, which can in turn lead to the septic syndrome and inflammatory injury to the lung. Clinical features, more than serum markers, have been the best predictors of whether lung injury will follow sepsis, indicating that the mere presence of mediators alone cannot cause ARDS and that there are individual susceptibility factors in the effects of these mediators. With the advent of monoclonal antibodies and new anti-inflammatory drugs, prevention of progression from sepsis to multiorgan failure may become possible. Pneumonia is the most common infection that complicates ARDS once it is established, and the mortality rate may approach 90%. The existence of acute lung injury, its predisposing conditions, coexisting illnesses, and the therapeutic interventions used for patients with lung injury all can interfere with lung host defenses and set the stage for bacterial infection of the already-injured lung. This infection appears to add to the propagation of the multiple system organ failure that has already begun. In the future, it may become possible to prevent this infection, which would be a welcome development, because currently, we are stymied in our efforts to diagnose and treat pneumonia in the setting of acute lung injury. Preventive efforts will follow from an understanding of the pathogenesis of pneumonia and in the future may include topical antibiotics, selective digestive decontamination, and prophylactic passive immunotherapy. PMID- 2268995 TI - Lung mechanics in the adult respiratory distress syndrome. Recent conceptual advances and implications for management. AB - Since the earliest description of the adult respiratory distress syndrome (ARDS), impaired lung compliance has been a key diagnostic feature. Newer data suggest that a clear understanding of the mechanisms of acute lung injury may be needed to select the ventilatory pressures and patterns of flow delivery required for optimal gas exchange, adequate oxygen supply to tissue, and avoidance of barotrauma. This discussion briefly reviews the ARDS-specific derangements of lung mechanisms, describes measurement techniques applicable to the clinical setting, and suggests ways in which such information can be used in patient management. PMID- 2268996 TI - Mechanical heart-lung interaction in the adult respiratory distress syndrome. AB - We have discussed the complex hemodynamic changes that occur throughout the respiratory cycle during spontaneous and mechanical ventilation. In patients, many cumulative factors account for the total hemodynamic burden of inspiration and expiration. Thus, the change in pleural pressure, ventilation rate, mode of ventilation, amount of spontaneous ventilation, underlying lung and cardiac disease, and intravascular volume status all affect cardiocirculatory equilibrium. In addition, in the patient with ARDS, various immune mediators that are released into the circulation will affect LV function. Knowledge of the effects discussed in this article will aid the physician in choosing therapeutic options for patients with ARDS. PMID- 2268997 TI - Oxygen supply and consumption in the adult respiratory distress syndrome. AB - Our understanding of acute hypoxemic respiratory failure has evolved continually over the past 100 years. Currently, much attention is focused on the peripheral consequences of the adult respiratory distress syndrome, because the systemic sequelae are a significant contributor to morbidity and death from the condition. The unexpected relation between O2 supply and uptake in the periphery of these patients could be a signal of occult tissue hypoxia. If so, this would have important implications for clinical care aimed at minimizing the multiple system organ failure that often develops. Alternatively, the increases in uptake seen when delivery is increased could arise in part from coupling error, uptake by nonmitochondrial oxidase systems, oxygen radical formation, and the normal increases in uptake seen in the range of relative O2 supply independence. Future evolution in our understanding of ARDS will require a careful evaluation of the adequacy of tissue oxygenation and the role of tissue hypoxia in this syndrome. Promising new approaches such as near-infrared spectroscopy and magnetic resonance imaging may help provide indices of tissue O2 supply limitation that complement regional measurements of tissue function. PMID- 2268999 TI - Radiologic considerations in the adult respiratory distress syndrome. AB - ARDS is the clinical consequence of acute lung injury that results in increased permeability edema. Distinct pathophysiologic stages are reflected in the radiographic evolution of the syndrome. Diffuse microatelectasis, proteinaceous edema fluid, and multifocal in situ pulmonary vascular occlusions characterize the acute stages of injury and result in the appearance of diffuse consolidations and occasional pleural effusions on the radiograph. In the chronic organizing stage of ARDS, the physiologic consequences of subsiding edema and tissue repair may be reflected by a transition to stable interstitial patterns. There is a high frequency of complications related to the decreased compliance of the injured lung that lead to interstitial emphysema and other barotraumatic complications. Survivors of ARDS exhibit various degrees of physiologic impairment and radiographic abnormality that may improve during the first year after survival. The relations between various indices of the severity of ARDS and the ultimate outcome are emerging. Debate continues about the specificity of the chest radiograph in distinguishing increased-permeability edema from hydrostatic edema. In fact, interstitial patterns and pleural effusions are observed in both. Nonetheless, the chest radiograph is a pivotal tool for monitoring patients at risk of serious morbidity from nosocomial lung infection, barotrauma, and the complications accompanying the use of invasive devices. It is hoped that as we develop a more uniform consensus on the clinical definition of ARDS and begin to classify patients according to specific clinical or physiologic observations, chest radiographic observation will acquire greater diagnostic and prognostic significance in these critically ill patients. PMID- 2268998 TI - Pulmonary endothelial cell injury and altered lung metabolic function. Early detection of the adult respiratory distress syndrome and possible functional significance. AB - Markers of endothelial cell damage or dysfunction may be sensitive probes for the detection of the earliest phases of acute lung injury and may be a guide to the severity of injury or response to therapy as well. Depressed lung metabolic function may contribute to the intrapulmonary or systemic pathophysiology of ARDS. PMID- 2269000 TI - Ventilatory strategies in the management of the adult respiratory distress syndrome. AB - This article review available strategies for mechanically ventilating patients with the adult respiratory distress syndrome. The authors first present the conventional strategies of mechanical ventilation: volume-limited mechanical ventilation with positive end-expiratory pressure (PEEP) at normal inspiratory expiratory ratios, the approach that has been the mainstay of ventilatory support since the initial description of PEEP. This discussion attempts to summarize the rationale and goals of treatment in a practical, clinically useful manner. The second section of the article reviews less conventional ventilatory approaches, including inverse ratio ventilation, extracorporeal techniques, high-frequency ventilation, prone position, and fluctuating PEEP, and attempts to review critically the available literature regarding their application. PMID- 2269001 TI - Pharmacologic treatment of the adult respiratory distress syndrome. AB - Adult respiratory distress syndrome is an inflammatory disorder of the lung parenchyma that results in severe respiratory failure. It is associated with sepsis syndrome and multiple organ failure and may be mediated by a variety of substances, several of which have been discussed in this article. Because sepsis syndrome, ARDS, and multiple organ failure are associated with a high mortality rate that has not been reduced significantly by supportive treatment, a rationale exists for therapeutic intervention with agents that affect the inflammatory cascade. Several of these agents, notably corticosteroids and prostaglandin E1, have been shown to be of no benefit in humans despite laboratory and animal studies suggesting their utility. Other agents, including surfactant, antiendotoxin antibodies, and NSAIDs, are undergoing clinical trials and may prove to be effective. A third group, including anti-TNF antibodies and pentoxifylline, are of theoretical benefit but await clinical trials. PMID- 2269002 TI - Pulmonary sequelae in survivors of the adult respiratory distress syndrome. AB - A spectrum of pulmonary impairment may follow an episode of the adult respiratory distress syndrome (ARDS). At one end of the spectrum is normal pulmonary function; at the opposite is severe impairment. The late pulmonary effects of ARDS usually lie between these two extremes. This article describes the pulmonary sequelae of ARDS, reviews information concerning factors that may influence these sequelae, and provides suggestions for clinical evaluation of ARDS survivors. PMID- 2269003 TI - Representations in animal cognition: an introduction. PMID- 2269004 TI - Event representation in Pavlovian conditioning: image and action. AB - In a typical Pavlovian conditioning experiment, a relatively insignificant event, the conditioned stimulus (CS), is paired with a biologically more meaningful event, the unconditioned stimulus (US). As a consequence of those pairings, the CS is thought to acquire response characteristics of the US. In this article I describe experiments with rats that suggest that under some circumstances, the CS acquires control of perceptual processing of the US, in the absence of that US itself. I present three kinds of evidence for this surrogate processing, which I liken to imagery or hallucination: (1) CSs come to control specific, sensory evaluative responses normally evoked only by the USs; (2) CSs can substitute for USs in the establishment of new learning about those USs themselves; (3) CSs can substitute for USs in the modulation of conditioning to other events, either overshadowing (interfering) or potentiating learning, in the same manner as the USs themselves. Finally, I compare these data with evidence for conditioned sensation and imagery in humans, and suggest that imagery may be a very basic process, evolutionarily derived from perceptual and conditioning processes adapted to deal with remote or absent objects. PMID- 2269005 TI - Levels of stimulus control: a functional approach. AB - This paper surveys some illustrative experiments on categorization of visual stimuli by animals other than human. The results suggest a classification of categorical powers in five steps from simple discrimination to rote and open ended categorization, to concepts and the use of abstract relations. Nonhuman animals evidently readily categorize up to the fourth level as here defined, which is the level of concepts. With difficulty, they can sometimes be induced to rise even to the level of abstract relations. It is at the level of abstract relations that a large gap opens up between human categorizations and categorization by other animals. PMID- 2269006 TI - The representation of social relations by monkeys. AB - Monkeys recognize the social relations that exist among others in their group. They know who associates with whom, for example, and other animals' relative dominance ranks. In addition, monkeys appear to compare types of social relations and make same/different judgments about them. In captivity, longtailed macaques (Macaca fascicularis) trained to recognize the relation between one adult female and her offspring can identify the same relation among other mother-offspring pairs, and distinguish this relation from bonds between individuals who are related in a different way. In the wild, if a vervet monkey (Cercopithecus aethiops) has seen a fight between a member of its own family and a member of Family X, this increases the likelihood that it will act aggressively toward another member of Family X. Vervets act as if they recognize some similarity between their own close associates and the close associates of others. To make such comparisons the monkeys must have some way of representing the properties of social relationships. We discuss the adaptive value of such representations, the information they contain, their structure, and their limitations. PMID- 2269007 TI - Representation of time. AB - Memory representation for time was studied in two settings. First, an analysis of timing in a laboratory analog of a foraging situation revealed that departure times from a patchy resource followed a Weber Law-like property implied by scalar timing. A trial-by-trial analysis was then pursued in a similar but more structured experimental paradigm, the Peak procedure. Study of covariance structures in the data implicated scalar variance in the memory for time as well as in the decision process, but the correlation pattern ruled out multiple access to memory within a trial. PMID- 2269008 TI - Alternative representations of time, number, and rate. AB - Three facts of time perception are described based upon a temporal generalization task for rats (the peak procedure) in which food reinforcement is delivered on half the trials following the first lever-press response after some fixed interval after signal onset. (1) The mean response rate as a function of time is a smooth, slightly asymmetric, function with a maximum near the time of reinforcement; (2) the response rate on individual trials is characterized by an abrupt change from a state of low responding to a state of high responding and finally another state of low responding (break-run-break pattern); and (3) the mean response rate in 12-s and 20-s peak procedures is similar when plotted against time relative to the time of reinforcement (superposition). An information-processing version of scalar timing theory is described and compared to an alternative connectionist version of scalar timing theory that involves multiple oscillators and an autoassociation network. Psychological, mathematical and biological descriptions of the two versions are described and some possible extensions of the connectionist version are proposed to deal with perception of number, rate, and spatial orientation. PMID- 2269009 TI - Honey bee cognition. AB - The visual memory of honey bees is stored pictorially. Bees will accept a mirror image reversal of a familiar pattern in the absence of the original, but prefer the original over the reversal; the matching system of bees, therefore, does not incorporate a mirror-image ambiguity. Bees will not accept a rotation of a familiar vertical pattern, but readily recognize any rotation of a horizontal pattern; the context-specific ability to make a mental transformation seems justified by natural contingencies. Bees are able to construct and use cognitive maps of their home area, though it is possible to create conditions under which they lack useful cues. Other experiments suggest that recruits, having attended a dance in the hive specifying the distance and direction of a food source, can evaluate the "plausibility" of the location without leaving the hive; this suggests a kind of imagination. PMID- 2269010 TI - Testicular cancer. PMID- 2269011 TI - Update: prostate cancer. AB - Prostate cancer represents a major health-care issue for older men. Recent technical advances in imaging, serum markers, and treatment hold great promise. Further insight into the natural history and biologic potential of this ubiquitous neoplasm is necessary before we can make rational decisions about early detection and newer treatment approaches. PMID- 2269012 TI - Polycystic ovary syndrome. AB - Polycystic ovary syndrome is a disorder of unknown cause characterized by anovulation, hyperandrogenism, and gonadotropin secretory abnormalities producing oligo-ovulation or anovulation. Hyperinsulinemia and insulin resistance are important features of this syndrome. Because other causes of androgen excess may produce similar clinical and biochemical findings, PCO remains a diagnosis of exclusion. Treatment is directed toward relieving symptoms of hyperandrogenemia in order to stimulate ovulation, correcting obesity, and inducing regular menses to reduce the risk of endometrial cancer. PMID- 2269013 TI - Risk factors for breast cancer. AB - Despite the numerous risk factors for the development of breast cancer that have been investigated, only a few demonstrate a clear association with breast cancer development. Female gender and increasing age are the most important factors, followed by factors involving a woman's menstrual, reproductive, and family history. The risks related to menstruation and reproduction are probably related to the duration of estrogenic breast stimulation. The relationship of family history and breast cancer risk is unclear, but there may be a true genetic basis. The previous occurrence of breast cancer (invasive or in situ), the presence of proliferative pathological changes, especially with atypia, and the presence of other malignancies (e.g., primary ovarian and endometrial cancer) are histological risk factors for the development of new or recurrent breast cancer. Radiation exposure, the use of exogenous estrogens (both estrogen replacement therapy and oral contraceptives), diet (especially fat consumption), and alcohol intake may all play a role in cancer risk. Certain medications as well as patient demographics may also have a weak association. Cigarette smoking, caffeine consumption, and stress presently have little support for an association with breast cancer risk. It should be noted that in only one in four patients can breast cancer be accounted for by the known risk factors. This demonstrates that although presently known risk factors may help in screening for the early detection of breast carcinoma, in its possible prevention by modulation of influenceable factors, and in advising patients about their risks, these factors are merely strong associations with breast cancer incidence and not actual causations. The mechanisms of the development of breast cancer are as yet unknown. PMID- 2269014 TI - Fertility-sparing treatment of patients with ovarian cancer. AB - The variety of malignant neoplasms produced by the ovary are legion. Each must be considered individually in the young woman with early disease who wishes to preserve her childbearing capability. The risks of conservative surgery are often low, and the patient can be so advised. Careful monitoring of this group of patients is essential regardless of the approach. PMID- 2269015 TI - Management of colorectal cancer. PMID- 2269016 TI - The emetic effects of cancer chemotherapy. PMID- 2269017 TI - The dimethylglyoxime test in the prevention and management of nickel dermatitis. PMID- 2269019 TI - Tattooing. PMID- 2269018 TI - A dermatologic diary. Portrait of a practice. PMID- 2269020 TI - The uncombable hair syndrome. AB - The uncombable hair syndrome was first described by Dupre as "cheveux incoiffables." Since that time more than fifty cases have been reported. We wish to present three more cases, review the salient features of the syndrome, and describe some new observations. PMID- 2269021 TI - Linear basal cell nevus. AB - We report a case of linear basal cell nervus occurring on the thigh of a forty five-year-old woman. In this lesion, the characteristic comedones were absent. Linear basal cell nevus is a rare, benign condition that must be differentiated from both basal cell nevus syndrome and linear basal cell carcinoma, either of which can be locally aggressive. PMID- 2269022 TI - Porokeratotic eccrine ostial and dermal duct nevus: a case of systematized involvement. AB - We describe a case of porokeratotic eccrine ostial and dermal duct nevus presenting as widespread, symmetrical lesions. To our knowledge, this represents the most extensive case of this entity reported to date. Both the localized and systematized variants of this nevoid condition are discussed. PMID- 2269023 TI - Influence of monaural plugging on postnatal development of auditory spatial sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus. AB - Postnatal development of auditory sensitivity in the big brown bat, Eptesicus fuscus, was studied by determining the auditory spatial sensitivity of inferior collicular (IC) neurons of juvenile bats which were raised under normal (control) or monaurally plugged conditions. The auditory spatial sensitivity of each IC neuron was determined by measuring its variation in number of impulses and minimum threshold to a best frequency sound delivered from different azimuthal angles under free field stimulation conditions. Monaural plugging was performed on different juvenile bats at 7, 14, and 35 days of age. Auditory spatial sensitivity was then determined for IC neurons of monaurally plugged bats at 58 69 days after birth. Monaural plugging did not alter the discharge pattern, distribution of best frequency and latency of IC neurons, but it raised the minimum threshold of IC neurons of plugged juvenile bats by an average of 21-24 dB. Monaural plugging also appeared to modify postnatal development of auditory spatial sensitivity. The auditory spatial sensitivity of IC neurons was sharper when the earplug was intact than when the earplug was removed. Thus, the distribution of response center and the spatial sensitivity of IC neurons of the monaurally plugged bats was more comparable to IC neurons of the control bats before the earplug was removed. These findings suggest that the neural circuits underlying auditory spatial sensitivity of IC neurons of the monaurally plugged juvenile bats have undergone modifications to compensate for the unnatural binaural disparity during postnatal development. The auditory spatial sensitivity was also determined for two control juvenile bats at 49 and 60 days of age and for an adult bat (more than 1 year). Our data show that auditory spatial sensitivity of IC neurons sharpens with postnatal age. Furthermore, the sharpening process appears to be still in progress even at 60 days after birth. PMID- 2269024 TI - Decentralization of superior cervical ganglia attenuates heat stroke formation in rabbits. AB - The effects of preganglionic decentralization of (sympathetic trunk resection) or post-ganglionic excision (ganglionectomy) of the superior cervical ganglia on cerebral blood flow and the formation of heat stroke were assessed in rabbits. An intravenous isotope method for external measurement of cerebral circulation time was applied to rabbits for determining cerebral blood flow. Heat stroke was induced by exposing animals to a high ambient temperature of 40 degrees C. The occurrence of loss of sensation, decreased muscle tone and unconsciousness was taken as the onset of heat stroke. The results showed that decentralization of the superior cervical ganglia enhanced the cerebral blood flow, whereas ganglionectomy reduced the cerebral blood flow. In addition, the latency for the onset of heat stroke and the survival time after the heat stroke were greatly prolonged by the former surgical procedure, but shortened by the later one. The data suggest that decentralization of the superior cervical ganglia attenuates formation or development of heat stroke by promoting an increase in cerebral blood flow in rabbits. PMID- 2269025 TI - Extracellular single-unit studies of suprachiasmatic neurons in brain slices. Effects of serotonin, dopamine, carbachol and LHRH. AB - Suprachiasmatic nucleus (SCN) is the major rhythm generating center in the central nervous system. Extracellular single-unit activities of the SCN neurons were recorded in brain tissue slices either from ovariectomized (OVX) rats or from OVX rats treated with estrogen (polyestradiol phosphate, PEP, 0.1 mg/rat, sc). Neuronal responses to luteinizing hormone-releasing hormone (LHRH) and various neurotransmitters, i.e., serotonin (5-HT), dopamine (DA) and carbachol (Carb, an acetylcholine agonist) were tested. A total of 137 units were recorded from OVX and 81 from OVX + PEP rats. The steady state firing rates of SCN neurons were between 0-9 spikes/sec in OVX and 0-23 in OVX + PEP group. Among them, most fired irregularly (86.9% in OVX and 71.6% in OVX + PEP rats), and a few fired regularly (10.2% and 25.9%, respectively). Few silent units were detected (2.9% and 2.5%, respectively). It seems that estrogen treatment somewhat increased the percentage of regular firing units. As for the agents tested in this study, LHRH by itself had no significant effect on the SCN neuronal activity; 5-HT affected more than 40% of the units, with about equal number of excitation (16.8%) and inhibition (24.4%), while Carb inhibited nearly half of the units tested (49.5%), excited only a few (10.3%). All the actions of these three agents were not significantly affected by in vivo estrogen pretreatment. Dopamine, however, excited more units (50%) in OVX than in OVX + PEP group (27.1%). Although LHRH had no direct effect by itself, it exerted a significant modulatory role on the actions of the other three agents. It either potentiated (42.9%) or inhibited (53.6%) the action of 5-HT, and it significantly potentiated the action of Carb (57.1%). For the action of DA, LHRH had a more significant potentiation effect on OVX + PEP than in OVX rats. (40.9% vs. 12.5%), while the inhibitory effect was the same. In conclusion, 5-HT, DA and Carb all exert significant effects on SCN neuronal activities. LHRH can have a modulatory role upon the action of 5-HT, DA and Carb, and estrogen pretreatment specifically affects that of DA in the SCN. PMID- 2269026 TI - The renal functions following a profound hypothermia in rats. AB - The aftereffects of renal function were studied in rats exposed to profound hypothermia and 5 min of cardiac arrest. All experimental rats were reanimated and survived at least 1 week. It was observed that the water intake and the basal renal excretion of urine, potassium and urea were decreased 24 hr after cooling, but did return to normal within 1 week. The renal handling of a large volume of infused saline was retarded 4 hr but recovered by the end of 24 hr after hypothermia. At both 4 and 24 hr after deep cooling, clearance of inulin and p aminohippuric acid showed there were no change in glomerular filtration rate and effective renal plasma flow. It was concluded that the renal function was altered shortly after deep cooling and 5 min of cardiac arrest, however, this alteration could be completely recovered thereafter. PMID- 2269027 TI - Morphological changes in the hypothalamic neurons of female rats exposed to continuous illumination. AB - The morphological changes of neurons in the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN), ventromedial nucleus (VMN), preoptic area (POA), supraoptic nucleus (SON) and arcuate nucleus (ARN) were studied in 16-18 month old Long-Evans female rats which had been exposed to continuous illumination (LL) for 11 months. Most neurons in those hypothalamic areas showed compact cytoplasm with abundant Nissl substances and evenly distributed chromatin. These morphological features were not found in the same hypothalamic regions of rats placed under a regular alternative light-dark regimen (14h light and 10h dark). These findings suggest that decreased melatonin and elevated estrogen levels induced by long-term exposure to LL might be involved in the morphological changes in hypothalamic neurons of female rats. PMID- 2269028 TI - [Clinical effect of China-made amrinone in the treatment of refractory congestive heart failure]. AB - Clinical and hemodynamic studies were carried out in 20 patients suffering from refractory congestive heart failure with invasive technique and non-invasive methods such as tolerance exercise test, 24-hour Holter monitoring, etc. Digitalis was then withdrawn and China-made amrinone (AMR) was administered orally for 15 days. All the indices mentioned above were repeated and each patient served as his own control. The results indicate that AMR can improve hemodynamic parameters as well as exercise tolerance. Holter monitoring revealed no significant increase in arrythmogenic potentiality. The total clinical effective rate was 95%. No severe side effects were found except thrombocytopenia observed in 20% of the patients. It is suggested that China-made AMR is effective in treating refractory congestive heart failure. PMID- 2269029 TI - [Mesothelioma and mesothelial hyperplasia]. AB - Twenty cases of pleural mesothelioma (2 localized and 18 diffuse malignant pleural mesothelioma), 6 cases of diffuse malignant peritoneal mesothelioma and 1 case of mesothelial hyperplasia were reported. The prominent clinical manifestations of malignant mesothelioma was serosal effusion. The exudate was bloody, mucinous and of high specific gravity. It contained numerous mesothelial cells. The diagnosis is difficult because mesothelial hyperplasia and other malignant tumors may mimic mesothelioma in some clinical aspects. Roentgenography, CT scan, cytology of serosal fluid and biopsy world help to establish the diagnosis of mesothelioma. Immunohistochemical features of 4 cases of mesothelioma is negative immunostaining for carcino embryonic antigen (CEA) and positive for keratin antigen. In one case ultrastructural examination showed characteristic features of epithelial mesothelioma cells. The average survival period in case of chemotherapy and/or surgical intervention in patients of this series was 31.3 months. Mesothelial hyperplasia has rather good prognosis; but the strategy of therapy may be conservative. PMID- 2269031 TI - [Clinical analysis and percutaneous transhepatic cholangiography drainage treatment of 25 patients with clonorciosis]. AB - The clinical data of 25 patients with clonorchiasis were analyzed. Some features shown by B-mode ultrasonography and percutaneous transhepatic cholangiography (PTC) were discussed. Application of percutaneous transhepatic cholangiography drainage (PTCD) for treatment of complete biliary tract obstruction caused by clonorchiasis was introduced. PMID- 2269030 TI - [Hepatitis D virus RNA in serum from patients with hepatitis B]. AB - To clarify the correlation of hepatitis D virus (HDV) infection and viral replication in liver diseases, the authors detected HDV RNA and serological HDV markers in serum from 285 patients with hepatitis B and 45 asymptomatic carriers of HBsAg. With dot blot hybridization, serum HDV RNA was detected in 8.8% (29/330) of the patients with HBV infection. The positive rate of HDV RNA in fulminant hepatitis was higher than that in benign hepatitis (15/74 vs 3/47, P less than 0.05). 10 of the 139 patients with chronic active hepatitis and 1 of the 6 cases with cirrhosis were positive for HDV RNA. However, all of the 19 cases with chronic persistent hepatitis and 45 asymptomatic carriers of HBsAg were negative fo, HDV RNA. Serological HDV markers, HDAgr anti-HD and IgM-anti HD, were determined with ELISA. HDV RNA was detected in all of the serum samples with positive HDAg and/or IgM-anti-HD, in 15 of the 26 cases with positive-anti HD and in 8 cases without HDV markers. Our results showed that 40 of the 330 patients with HBsAg were infected by HDV. This investigation suggests that HDV is one of the etiological factors for fulminant hepatitis and chronic active hepatitis. PMID- 2269032 TI - [Comparison of colloidal bismuth subcitrate with ranitidine in healing and relapse of Campylobacter pylori-associated duodenal ulcers]. AB - Eighty patients with Campylobacter pylori-associated duodenal ulcer disease were randomly allocated to receive colloidal bismuth subcitrate (CBS)tablet 120 mg four times a day or ranitidine 150 mg twice daily in a trial comparing the effects of these drugs in short-term healing and post-healing relapse rates of duodenal ulceration. At 8 weeks 88.1% (37/42) of those on CBS and 92.1% (35/38) of those on ranitidine had ulcers healed. The difference is not significant. After ulcer healing, the cumulative rates of relapse, as determined endoscopically, for symptomatic and asymptomatic ulcers were 19.4% (6/31) for CBS and 46.7% (14/30) for ranitidine at 6 months (P less than 0.05) and 41.9% (13/31) for CBS and 73.3% (22/30) for ranitidine at 12 months (P less than 0.05). As campylobacter pylori was cleared in 35 of the 42 patients (83.3%) in the CBS group, while only one of the 38 patients (2.63%) in the ranitidine group (P less than 0.005), it is possible that the clearance of Campylobacter pylori by CBS is instrumental to the reduction of the rate of reulceration. PMID- 2269033 TI - [An analysis of 26 cases of chronic myelomonocytic leukemia]. AB - Chronic myelomonocytic leukemia (CMML) is a polymorphous malignant hematological stem cell disorder, characterized by abnormal hyperplasia of mature or immature cells of both monocytic and granulocytic series and with abnormal cellular morphology. It is an independent entity of chronic leukemia, as its prestage course is manifested by refractory anemia with monocytosis and the disease gradually evolves to CMML. In some cases, it finally becomes acute leukemia. In this study, the average white cell count of the patients was 29.3 x 10(9)/L.14 cases had leucocytosis, 7 leucopenia and 5 normal count. The absolute value of monocytes was 19 x 10(9)/L and the proportion of monocytes was 10-87%, with an average of 49%. In the leukopenic group with white cell count less than 4 x 10(9)/L, the absolute value of monocytes was less than 1 x 10(9)/L in 5 of the 7 cases. However, it was noticed that all the 5 cases had a proportion of monocytes greater than or equal to 10%. The authors would like to take this percentage as the diagnostic criteria for CMML, which is different from that adopted in FAB classification of 1982 as well as in the literatures. Statistics showed that P value of M/E, Mo/E, Mo/M were of apparent significance in the differentiation of CMML from normal controls and patients with other hematological diseases such as RA, RAEB, CML, CNL, M4 and M5. PMID- 2269034 TI - [Clinical and experimental study of treating aplastic anemia with fetal liver cell suspension and fetal liver cell-free suspension]. AB - Fresh fetal liver obtained from 3- to 6-month fetus was prepared. Fetal liver cell suspension (FLC) or fetal liver cell-free suspension (FLCF) were then transfused into two groups of patient of aplastic anemia. 15 of 21 patients of aplastic anemia treated with FLC showed reconstitution of haemopoietic function or improvement of peripheral blood pictures, while 27 of 30 patients treated with FLCF showed reconstitution or improvement. It is verified that there is a stimulating factor for CFU-CM, BFU-E, and CFU-E and also a immunologic stimulant for improving the nonspecific immunologic function of the organism as shown by clinical analysis and experimental study. It is obvious that the therapeutic effect of FLCF is much better than that of the FLC. PMID- 2269035 TI - [Treatment of hypoparathyroidism with 1 alpha-hydroxyvitamin D3]. AB - 2 male and 17 female patients with hypoparathyroidism including 7 idiopathic, 11 surgical and 1 pseudohypoparathyroidism received 1 alpha-OHD3 at a mean daily dose of 2.7 +/- 0.7 microgram (1.5-4.0 micrograms) combining with calcium 1 g for 14 weeks. The mean age of the patients was 37 +/- 9 old years and the mean course of disease was 15 +/- 10 years. The symptoms and signs of hypocalcium disappeared in 1-3 weeks after therapy, meanwhile the serum ionized calcium (Ca++) and total calcium (TCa) increased from 0.84 +/- 0.02 to 1.03 +/- 0.01 mmol/L and from 6.90 +/- 0.22 to 8.70 +/- 0.20 mg/dl (P less than 0.001) respectively. The serum Ca++ and TCa increased to normal volume in 58% and 63% patients respectively. The concentration of serum 1,25 (OH)2 D3 elevated significantly from 19.5 +/- 1.1 to 29.1 +/- 2.4 pg/ml (P less than 0.01 n = 17). The lever of urinary hydroxyproline was no significant change. The serum phosphate reduced markedly from 5.50 +/- 0.2 to 4.80 +/- 0.2 mg/dl (P less than 0.01). The serum Ca++ and TCa changed to the primitive level when we stopped to use 1 alpha-OHD3 alone for 1-3 weeks. No significant side effects were found. It might be suggested that 1 alpha-OHD3 is effective and safe in treating hypoparathyroidism because calcium absorption in intestine is promoted by 1 alpha-OHD3. PMID- 2269036 TI - [Behavior of beta 2-microglobulin in patients undergoing blood purification]. AB - The Behavior of beta 2-microglobulin (beta 2m) in various modes of blood purification was studied. Serum beta 2m concentration was 26.1 +/- 9.9 mg/L in 39 patients on maintained hemodialysis (HD) and 20.6 +/- 5.3 mg/L in 26 patients on CAPD. In both groups, beta 2m was significantly higher than normal (P less than 0.01) and it was positively correlated with the duration of dialysis. However, patients surviving more than three years would show lower beta 2m in the CAPD group than those in the HD group. The mean value of beta 2m clearance was 108 mg during hemofiltration (HF) with polyamide membrane and 38.5 +/- 14.4 mg daily in CAPD. Not only very little. beta 2m could be removed on HD but a rise of beta 2m was observed after the procedure, even if it was corrected for hemoconcentration. A negative correlation was found between delta beta 2m and delta osmolality after HD (r = 0.58, P less than 0.05), but delta beta 2m would be decreasing if a cuprophan membrane dialyzer was reused for HD, and the result was the same if using the same membrane in isolated ultrafiltration (P less than 0.01 in all). These results suggested that the rise of beta 2m during HD with cellulose membrane may be due to increased release of beta 2m owing to the poor biocompatibility of the membrane as well as the generation of beta 2m on account of reduced plasma osmolality. PMID- 2269037 TI - [Changes in fluorine metabolism during the treatment with calcium-magnesium preparation in 60 cases of endemic fluorosis]. AB - Using the method of metabolic balance, we investigated the fluoride metabolism and its change during calcium-magnesium preparation treatment in 60 cases of endemic fluorosis. We found that in patients with fluorosis the intake of fluoride and the levels of urinary, fecal and serum fluoride were several times higher than those of normal controls (P less than 0.01), that the intestinal fluoride apparent absorption rate was 1.5 times higher than that of normal controls (P less than 0.01) and that at a given dietary level of fluoride, there existed a balance of fluoride metabolism. Fluoride intake was positively correlated with intestinal fluoride apparent absorption rate (r = 0.375, P less than 0.01). The combination of calcium and magnesium preparation with fluoride led to decrease of intestinal fluoride apparent rate (P less than 0.05) and increase of fecal fluoride output (P less than 0.05). It seems reasonable to treat fluorosis with calcium-magnesium preparation. PMID- 2269038 TI - [Contractile function of the gallbladder after gastrectomy]. AB - Gallbladder contractile function was observed by B-mode ultrasonography on patients with radical gastrectomy for gastric carcinoma (20 cases), with subtotal gastrectomy for peptic ulcer (36 cases), and with highly selective vagotomy (7 cases). Thirty-one preoperative patients with peptic ulcer were used as control. It was found that within one month after radical or subtotal gastrectomy the average area and the volume of the gallbladder became much larger than that found in control group. The empty rate of the gallbladder was found decreased and the remainder bile increased. Early stage gallstones were found in two cases 11 and 13 months after gastrectomy. The inner diameter of the common bile duct was increased after radical gastrectomy. No definite relationship was found between gallbladder contractile disfunction and the mode of gastroenterostomy. It was also found that highly selective vagotomy had only slight influence on the biliary tract. These results suggest that gastrectomy has significant influence on the function of biliary tract and plays an important role in the formation of gallstones. PMID- 2269039 TI - [Duodenal Brunner's gland adenoma: a report of 2 cases]. AB - In this communication, the authors presented 2 cases of duodenal Brunner's adenoma. Major clinical features included bleeding and nonspecific upper GI symptoms. It was the authors belief that X-ray examination, endoscopy and laparotomy were most often used diagnostic means, and an operation was indicated should endoscopic resection be unsuccessful. PMID- 2269040 TI - [Tumors of the spine: a clinical study of 80 cases]. AB - From February 1972 to December 1988, 80 cases of spinal tumor were treated in this hospital. 37 of these cases were primary tumor and 43 cases were secondary tumor. Most of the primary tumors were angioma and massive osteolysis, most of the metastatic tumors were from gastrointestinal and pulmonary carcinoma. The time of onset in both groups within half a year were 54.2% and 65.1% respectively. The dominant symptoms were pain, mass and paralysis. Except 4 cases which involved more than one vertebrae, all others involved only one vertebra. Primary tumours were mostly found in the sacrum (41.1%) and metastatic tumors were mostly found in the thoracic spine (65.2%). Sixty-three patients were treated by different combinations of operative methods. Eleven primary malignant tumor and 16 metastatic case had been followed-up for 3 months to 3 years, 25 cases died. The rate of misdiagnosis was 21.25%, which mainly occurred in the secondary group. The causes of misdiagnosis were analysed. PMID- 2269041 TI - [Significance of CT scanning in diagnosis of herniated lumbar disc]. AB - During March 1986 to September 1988, 52 patients complaining lumbago and/or sciatica diagnosed by CT scanning as herniated lumbar disc were operated upon. The accuracy of CT diagnosis for lumbar disc herniation proved by surgery was 47 cases (90.4%). CT findings and surgical findings did not accord in 5 cases. Of these, some were because of technical problems of the CT scanning and some were faults of surgical technique. The merits and faults of CT scanning for diagnosis of protrusion of lumbar disc and its CT manifestations were discussed. PMID- 2269042 TI - [Resection of intracranial aneurysms: report of 10 cases]. AB - Resections of intracranial aneurysms were performed in 10 cases. There were 4 PCAAS, 1 ACOAA, 1 callosmarginal, 1MCA, 1 PCAA, 1 PCHAA, and 1 ICAA aneurysms. The diagnostic methods and operative indications are discussed. The histological changes of these removal aneurysms were discussed also. There were no mortality and severe complications. The surgical results were satisfied. PMID- 2269043 TI - [Treatment of neuromyelopathy after repair of myelomeningocele or meningocele]. AB - Forty-two cases of neuromyelopathy after lower thoracic lumbosacral myelomeningocele or meningocele repairment were reported. The repaired ages were from newborn to 6 years old. Subsequently progressive paralysis of lower extremities with incontinence of bowel and urination were seen after the primary operation. It may be due to "tethered spinal cord syndrome" or postoperative adhesion. Removal of the scar of adhesions over the lower thoracic and lumbosacral region and neurolysis were performed. Following 3-30 months after operation we found out that recovery of bowel function in 38 cases (90.5%). Active urination was recovered in 13 cases (31%) and improved in 22 cases (52.4%). Motor dysfunction and paresthesis of the lower extremities were alleviated in 19 (73.1%) of the 27 cases. No case revealed aggravation of symptom due to operative procedure. PMID- 2269044 TI - [Acute focal bacterial nephritis: report of 7 cases]. AB - Acute focal bacterial nephritis (AFBN) is an inflammatory disease. However, The patients with AFBN were frequently misdiagnosed as renal tumors due to the imaging examination (X-ray, IVP and B ultrasound, etc) showed presenting a solid mass in the kidney. In this article, 7 cases of AFBN were reported. There were 5 males and 2 females and the mean age was 22.7 years (15-35). In the first two cases, nephrectomy was carried out due to misdiagnosis and the later five cases were all cured with antibiotics. The author considers that the diagnosis of AFBN should be relied mainly on clinical symptoms and should not be based only on imaging examination. The dynamic imaging examination, especially before and after the treatment of antibiotics, is important for the diagnosis of the diseases. According pathologic procedure and imaging figure of the disease, from the point of view of surgery, the author recommends "Renal Inflammatory Pseudotumor" as the term of the disease. PMID- 2269045 TI - [Xanthogranulomatous pyelonephritis complicated by urolithiasis in upper urinary tract]. AB - Twelve cases of xanthogranulomatous pyelonephritis (XGPN) complicated by urolithiasis in upper tract were presented in this study. Fifty-four cases of XGPN, including 12 cases of this study, reported in China were clinically analysed in the article. All cases were with one suffered kidney, 57.4% of the cases had both XGPN and urolithiasis, 27.8% had the history of urinary infections, 99.0% had function-impaired kidney or renal failure. XGPN was frequently mis-diagnosed as renal cancer, renal tuberculosis and renal abscess etc. The diagnosis and treatment of XGPN are discussed. PMID- 2269046 TI - [Free skin flap for wound infection]. AB - Since 1979, free skin flaps (FSF) have been used for repairing infected wounds in 32 cases with the sequence of 31 cases succeeded and 1 case failed. Among them, 27 cases (84%) were I stage healing and 4 cases (12.5%) were II stage healing. The patients whose infectious surface of wound with exposure of bone, articulation and tendon can not repair with skin grafting or near skin flap were chosen to have this operation. However, the blood vessels in the surface of wound which can be supplied to anastomosis were also necessary. The most important thing for the operation was determination of the opportunity making out the major bacteria infected and debridement entirely. The bigger the blood vessel calibre of FSF selected, the better the surface of wound healing. In this group, 4 cases appeared crisis of blood vessels. Whether it is associated with inflammation of wound is discussed. PMID- 2269047 TI - [Klinefelter's syndrome: report of 35 cases]. AB - Thirty-five cases of Klinefelter's syndrome are reported. All patients had special type of chromosome of the disease. The authors deduce that the rate of sex chromosome distortion is concerned with the time of baby and the age of the mother. The special type of chromosome is reliable basis of the diagnosis in addition to the symptoms. After getting treatment with methyltestosterone, the testis of those patients could grow larger but could not produce spermatozoon. The authors found that the traditional Chinese medicine "Sheng Jing San" could not only help make testis larger but also could contribute to producing spermatozoa. PMID- 2269048 TI - [Gallbladder bile proteins in patients with gallstones and normal controls]. AB - The concentration of total protein and 17 different proteins in gallbladder bile of patients with gallstones and normal controls were analyzed. The result showed that the amount of total protein and 11 of 17 proteins was much higher in patients with cholesterol gallstones than that of normal controls. These proteins may be involved in the nucleation of cholesterol crystal in gallbladder bile of patients with cholesterol gallstones. The nucleation activity titre (NAT) of gallbladder bile of patients with gallstones and controls was determined. The NAT of gallbladder bile of patients with gallstones was 1/25-1/100 and that of controls was 1/100-1/6400. There was a statistically significant difference of NAT between patients with cholesterol gallstones and normal controls. PMID- 2269049 TI - [Intrahepatic IgA and secretory component distribution and the mechanism of hyperSigAnemia]. AB - Using immunohistochemical techniques, the authors observed the distribution and localization of IgA and secretory component (SC) in normal and hepatolithiasis livers, and measured the serum level of IgA by means of sandwich enzyme immunoassay (EIA). It was found that in normal livers positive reaction for SC and IgA could only found in epithelial cells of biliary canals. While in hepatolithiasis livers strong positive reaction for IgA and SC were also found in dilated bile canaliculi and the sinusoids. These results suggest that the epithelia of biliary canals take part in the formation and transferring of IgA and the backflow of IgA into blood stream under high pressure may cause hyper SIg A nemia. PMID- 2269050 TI - [Ultrastructure and elemental composition of pancreatic stones]. AB - Four patients with pancreatic duct stones (PDS) and one with calcium deposits (CD) were diagnosed and surgically cured. The ultrastructure and elemental composition of PDS were studied by scanning electron microscopy and energy dispersive X-ray fluorescence. The results indicated that the outer shell of PDS, with dense texture, contained 96.29% of calcium (Ca), while the amorphous reticular inner nidus mainly contained sulphur (S) and chlorine (Cl). CD and PDS were manifestations in the process of pancreatic stones (PS) formation at different stages. As regards the formation of PS, the depressed gene expression played a key role in the reduction of PSP (Pancreatic Stone Protein), which made pancreatic acini reduce PSP biosynthesis rates. The consequence arising therefrom was that the supersaturated calcium carbonate (CaCO3) in pancreatic juice became inadequately inhibited. Thus the calcium carbonate became crystallized and deposited onto the reticular inner protein nidus (RIPN), which developed from the compilation of micro-protein-plugs that had grown from pathologically hyperconcentrated total proteins (mainly containing lactoferrin) in pancreatic juice. The RIPN gave a basis on which the calcium carbonate precipitated and formed PS. PMID- 2269052 TI - [Alternation of plasma fibronectin concentration after fracture and relationship with infection]. AB - Plasma fibronectin concentrations were measured in 78 patients with traumatic fracture and 80 healthy people as a control. The results showed that plasma fibronectin concentrations of the patients without complicated infection were significantly decreased 5 to 48 hours after fracture. As comparison with the control, the mean decrease was 56 (16.9%; P less than 0.01), 121 (36.5%; P less than 0.001) and 71 mg/L (21.4%; P less than 0.001) at 5.24 and 48 hours respectively, and restored to the levels of the control at 4 days. In the patients complicated infection, plasma fibronectin concentration was not recovered at 14 days after fracture. The mean decrease was 96 (28.9%; P less than 0.001); 148 (44.6%; P less than 0.001), 119 (35.8%; P less than 0.001), 83 (25.0%; P less than 0.001), 59 (17.8%; P less than 0.01) and 43 mg/L (13.0%; P less than 0.01) at 5.24, 48 hours, 4.7 and 14 days, respectively, as comparison with the control. The results suggest that plasma fibronectin concentrations in the patients with fracture without complicated infection are temporarily decreased and rapidly recovered, but, in the patients with complicated infection, the low fibronectin levels are continued and render the patients more susceptible for bacteria and thus result in complicated infection. Plasma fibronectin can be used as a valuable index to prevent and treat complicated infection after traumatic fracture. PMID- 2269051 TI - [Immunopathological factors influencing the prognosis after resection of lung cancer]. AB - 118 surgical specimens were obtained from patients with lung cancer treated in our hospital during the period of 1977-1983 and tested with carcinoembryonic antigen (CEA), ABO (H) isoantigen and Concanavalin A (ConA). The results showed that the CEA assessment, which give no prognostic significance for long-term survival (P greater than 0.05), would be useful in predicting short-term (6 month) out come (P less than 0.05). All patients with positive ABO (H) test for squamous cell lung carcinoma survived at the end of five years. As for ConA, no definite link has been found with the prognosis. PMID- 2269053 TI - [The role of oxygen free radicals in craniocerebral injury]. AB - Serum LPO content was measured by means of TBA in 41 patients suffering from craniocerebral injury in present study. The relationships between OFR and progressing course of craniocerebral injury, level of LPO and patient condition of an injury and prognosis were analysed. Results showed that serum LPO increased obviously in 24 hours after injury. The more severe the condition of an injury was, the higher the serum LPO content was, the worse prognosis would be. Serum LPO content increased statistically in group of death in 24 to 72 hours after injury, while it didn't change significantly in group of survival. The author suggest that the reaction of OFR enhanced after craniocerebral injury, and which was an important factor giving rise to secondary brain injury. Measurement of serum LPO content plays an important role in estimating the patients condition of injury and their prognosis. PMID- 2269054 TI - [Experimental study of removal of sublaminar wires after spinal fixation]. AB - The result of experimental study of removal of sublaminar wires was reported. The experimental shows that sublaminar wires when with drawn at 45-degrees is safer than that at 90-degrees. Because of bony fusion, clinically could be drawn out only vertically either by rolling it up ward or down ward confirmed that there is no difference between this two methods. The cut end of wire should be short and straight. All the fixing wires became useless because of their loosening. Impressions were found on the inner face of lamina, fibrous sheaths. There is no different reactions between twisted and parallel double wires, but we recommend double parallel wires. PMID- 2269056 TI - [Embryonal neurotransplants halt degenerative processes in nerve cells in the recipient's brain]. PMID- 2269055 TI - [An experimental study on the role of beta-endorphin in the pathogenesis of acute pancreatitis and the effects and mechanisms of naloxone]. AB - 120 SD rats were randomly divided into three groups: the sham operation group, the AP (acute pancreatitis) group, the naloxon treated group. AP was induced by intraductal injection of 5% sodium taurocholate solution. Naloxon was given intramuscularly at the dosage of 0.1 g/100 gw immediately after the injection and 90 minutes later. The survival rate and the mean survival time of the rats during 3 days after the induction of AP were determined. The pancreata were sampled for semiquantitative histopathologic evaluation. By using the fractional indicator distribution technique with 86 RB, QP/CO and pancreatic tissue perfusion performed 1 and 6 hours after the induction of AP, the amount of beta-endorphin in the hypothalamus and pituitary was measured 1 and 4 hours after the induction of AP. It was found in the naloxon treated group, the pancreatic blood flow and tissue perfusion was greatly increased, the mortality rate was decreased, and the rats survival time was significantly prolonged. The results suggest that: (1) The hemodynamic changes play an important role in the pathogenesis of AP. (2) Beta Endorphin may play a role in the pathophysiological process of AP. (3) naloxon has good therapeutic effects on AP. PMID- 2269058 TI - [Regenerative processes in rat gastrocnemius muscles upon their xenotransplantation to Mongolian gerbils]. PMID- 2269057 TI - [Distribution of fibronectin, laminin and neurofilaments in adult rat brains upon transplantation of embryonal nerve tissue]. PMID- 2269059 TI - [The use of 31P NMR in the study of in vivo dynamics of phosphorus-containing metabolites in the rat brain after frontal lobectomy]. PMID- 2269061 TI - [Periodontal status of abutments of resin-bonded bridges]. AB - In a combined retrospective longitudinal study an evaluation of different dental and periodontal indexes (tooth mobility, probing pocket depth, plaque index, sulcus bleeding index, probing attachment level) in 62 patients with 77 resin bonded bridges was performed. The direct comparison between test (abutment) and control (non-abutment) teeth revealed no differences at the day of evaluation in comparison to the date of incorporation. The longitudinal evaluation resulted in more favourable values at the day of evaluation in comparison to the date of incorporation for both the test and control teeth. Despite the altered contour of the abutment teeth, resin-bonded bridges seem not to change the periodontal status in a long-term evaluation, if good patient cooperation and regular care by a dental hygienist are guaranteed. PMID- 2269062 TI - [Reinserting loosened bonded bridges]. AB - 203 bonded bridges were reinserted under standardized conditions. In 44 cases there was a loss of primary retention and in another 22 cases the bridges were removed for repair of a pontic. The bridges reinserted after loss of primary retention were significantly less successful (26%) than the bridges with primary retention (87%). The success rates of the bridges reinserted after deliberate removal (91%) was significantly higher than that of the bridges reinserted after loss of primary retention (48%). PMID- 2269060 TI - [Healing and integration of ePTFE membranes]. AB - In this study 40 patients with adult periodontitis received periodontal therapy with ePTFE membranes according to the principle of guided tissue regeneration. Membranes were subgingivally implanted for a period of 4 to 6 weeks. The tissue response was examined clinically and, in 7 cases, also histologically. After removal of the membranes, the membranes themselves and biopsies of the underlying regenerated tissue were prepared for light- and transmission electron microscopy. Clinically most cases showed membrane exposure with recessions and gingival pockets between membrane and gingiva. Histologically all exposed parts of the membranes were contaminated by microorganisms. In the superficial layers of the biopsies microorganisms were found between neutrophils, degenerated collagen fibrils and necrotic cell components. PMID- 2269063 TI - [A procedure for testing local anesthetics]. AB - A method for testing intensity and duration of the effect of local anaesthetics is presented. The assessment of effectiveness is based on the subjective perception threshold after painful electrical tooth pulp stimuli. With respect to its practical applicability the method is tested in a clinical study using three commercial local anaesthetics. The results prove the possibility of giving reproducible and quantitative statements concerning the time course and intensity of anaesthesia. Using this method, only a restricted number of subjects is necessary for estimating the differences in the basic features of different local anaesthetics. PMID- 2269064 TI - [Epidemiologic studies in 14 to 16-year-old pupils in Lippstadt]. AB - In a cross-sectional survey we obtained figures on the current state of periodontal health of 14 to 16-year-old pupils who attend different types of schools in Lippstadt, a town with a balanced social structure. A rate of 82% of gingivitis morbidity was found, including an average CPITN of 0.49. Nevertheless, only 43.8% of the examined periodontia showed signs of gingivitis. Analysis of the individual values showed marked differences related with age, sex and type of school. PMID- 2269065 TI - [Interaction of dental treatment anxiety and oral health]. AB - Measurements of oral health (PBI, DMFS), dental treatment anxiety (DAS) and frequency of dental utilization were taken in a sample of 474 dental patients. Regression analysis shows that DAS scores are significantly correlated with DS, but not with MS and FS. Dental anxiety has a negative impact on the frequency of dental utilization, which is a predictor variable of oral health status. These results permit the conclusion that our attention should be focussed on reducing dental treatment anxiety to improve oral health. PMID- 2269066 TI - [Time of extraction and cavity position in in-vitro tests of dentin adhesives]. AB - Cylindrical cavities were prepared in different tooth segments (coronal, cervical and radicular) and at different times (1 hour, 1 day, 1 week and 1 month) after extraction into face-ground dentin surfaces of extracted teeth. The cavities were filled with composite resin materials using different dentin adhesives. Before and after thermocycling (TC) the marginal adaptation was evaluated using defined criteria. The statistical evaluation did not show any significant differences (p greater than 0.01) after TC within the different groups of dentin adhesives. For in vitro tests of dentin adhesives neither the position nor the time of extraction decisively influences the process. PMID- 2269067 TI - [Measurements of the elastic and permanent deflection of MOD restorations during vertical loading]. AB - In a loading device the mesio-distal deflection of mod restorations caused by different forces is measured reproducibly with inductive transducers. The accuracy of the measurements is about +/- 1 micron. Uncemented inlays of a soft gold casting alloy deflect 40 microns under load and 25 microns permanently; for an extra hard gold casting alloy the maximum values amount to 30 and 5 microns, respectively, and for a silver palladium alloy to 15 and 2 microns, respectively. Restorations of a non-gamma-2 amalgam reveal deflections within the range of accuracy near 2 microns. PMID- 2269068 TI - [Deflection and marginal leakage in cemented MOD inlays under loads parallel to the tooth axis]. AB - Cemented inlays made of a soft and an extra hard gold casting alloy are subjected to load cycling with 50-200 N. The mesiodistal deflection is determined and marginal leakage is shown by dye penetration. Soft alloy inlays deflect significantly more, nearly 50% exhibit dye penetration caused by microleakage. On average, deflection does not occur with the extra hard alloy, dye penetration caused by microleakage takes place among 25% of the inlays only. PMID- 2269069 TI - [Air vents for improved accuracy of fit of cast inlays]. AB - The advantages of air vents in the production of extensive cast gold inlays and partial crowns were examined in an in vitro study aimed at reducing the occurrence of open margins in the proximal surfaces. The results of this study with a total of 44 casts showed that a closer marginal fit is achieved by the use of additional air vents. PMID- 2269070 TI - [Titanium: a new avenue for inlay and partial crown technique?]. AB - Inlays and partial crowns made with a new titanium casting system were studied for open margins. The rather heterogeneous results do not satisfactorily stand comparison with conventional methods and thus the clinical application of this system does not seem to make sense. PMID- 2269071 TI - [Experimental studies on the reproducible precision of fit of ceramic inlays]. AB - Three different types of ceramic inlay materials (Dicor, Biodent-Inlay-Keramik, Cerec) were evaluated for precision of reproduction and dimensional fit. The findings of this study revealed that laboratory-made restorations displayed satisfactory characteristics of reproduction except for the edges. Furthermore the initial fit of these materials was comparable to the fit of gold restorations. The Cerec-inlay system by contrast displayed insufficient reproduction characteristics especially at lines, angles and edges. The average marginal gap of Cerec inlays measured was 154 microns. General guidelines for cavity preparations based on the present findings are discussed. PMID- 2269072 TI - [Marginal fit of ceramic and composite inlays in vitro]. AB - Direct and indirect composite and ceramic inlays exhibit a space between inlay and tooth, which is filled with a luting composite resin. The aim of the present study was to evaluate the influence of the width of this space upon the quality of the marginal seal of the inlay system. The marginal quality of class II-inlays with small (0.2 mm) and large (0.4 mm) spaces was examined using quantitative SEM analysis and dye penetration. Regular class-II composite fillings served as controls. After thermal and mechanical loading the composite inlays with the wider composite layer showed more marginal gaps than both groups of ceramic inlays. The ceramic inlays did not show a significant deterioration of the margins. The least amount of dye penetration was observed in ceramic inlays with a wider composite layer at the interproximal cavity wall. Composite fillings showed more dye penetration than inlays. PMID- 2269073 TI - [Ridge stabilization with adhesive inlays in MOD cavities]. AB - The flexural rigidity of the buccal cusps of upper premolars was determined under a vertical load of 100 N by use of displacement transducers. The stiffness of the cusps was higher when the cavities were restored with cast gold onlays or with composite or ceramic inlays luted with composite resin. In most cases a decrease in cusp stiffness was observed after thermocycling of the teeth restored with composite or ceramic inlays. With amalgam restorations or cast gold inlays, the flexural rigidity of the cusps was not higher than that of the unrestored cavities. PMID- 2269074 TI - [Effect of cavity design on the marginal fit of Class I composite fillings]. AB - 16 butt joint (Group A) and 16 beveled (Group B) class I cavities were prepared in extracted molars and filled with two hybrid composite resin materials using the enamel etching technique. Replicas were obtained before and after thermocycling (TC) and a computerized quantitative margin analysis was carried out in the SEM. Statistical analysis revealed significant differences (p less than 0.01) between the two groups only after TC. Group B showed significantly less marginal openings than Group A (A: 50.7%, B: 8.4%) after TC. Class I cavities for hybrid composite resin materials should be beveled. PMID- 2269075 TI - [Color stability of light curing composites]. AB - Eight commercial and two experimental light cured composite have been tested for color stability after experimental aging. Color differences were measured by computer-controlled spectrophotometry and expressed in terms of L*A*B* color coordinates (CIELAB). Although three composites with a high content of anorganic filler showed the best color stability and the material with the lowest anorganic filler content showed the greatest discoloration, there was no strong correlation between the amount of anorganic filler on the one hand and color stability after experimental aging on the other. PMID- 2269076 TI - [Shear bond strength between composite inlay and luting composite resin]. AB - The shear bond strength between composite inlay materials and luting composite resins was measured under different storage conditions and using different finishing techniques. The initial shear bond strength was distinctly higher with light-cured composites subjected to secondary light and heat cure (56.7-81.1 MPa) than with a heat- and pressure-cured material, where appreciable bond strength was achieved only after sandblasting of the composite surface (18.8 MPa). In general, water storage of the samples for 30 days with intermittent thermocycling adversely affected the bond strength. The influence of secondary light and heat curing on the bond strength of primarily light-cured composites was highly dependent on the material used. PMID- 2269077 TI - [SEM study on finishing the joint between inlay and luting composite resin]. AB - This in vitro study compared different methods of finishing luting composite resin spaces after insertion of composite resin inlays. SEM-evaluation revealed significant differences between the various finishing methods. Best results with high rates of perfect margins were obtained by use of twelve-fluted carbide burrs followed by surface polishing with silicone points. PMID- 2269078 TI - [The influence of cavity preparation on the width of marginal gaps in Cerec inlays]. AB - In a study of the influence of the proximal box shape on the marginal fit of Cerec inlays, MOD cavities were prepared in 10 extracted teeth. One box was prepared with sharp edges as recommended by Mormann (1989), the other was conventionally U-shaped. The width of the marginal gap was measured with a microscope at five different points. The results showed with high significance that the marginal gap of the U-shaped box preparation is smaller. It is recommended to use conventional U-shaped proximal box preparations for Cerec inlays, too. PMID- 2269079 TI - [Studies on the composite joint in Cerec inlays]. AB - In an in vitro study 32 ceramic restorations were constructed using the Cerec system and adhesively fixed in cavities prepared in extracted teeth with Dual Cement according to the supplier's instructions. The restored teeth were then histologically prepared and the joints between cement and inlay morphometrically evaluated at eight defined sites. The measurements showed average values of 118 microns with a standard deviation of 53 microns. It is particularly interesting to note the extremely great range of variation between the lowest and the highest value. The measured widths of the joints must be considered as a weakness of the system, because clinically they may result in wash-outs and material collapses in the long run. So far, no long-term studies have been conducted yet to investigate this effect. PMID- 2269080 TI - [Fine polishing of Cerec inlays using diamond polishing systems]. AB - The surface roughness of Cerec-inlays after polishing with diamond polishing pastes or Diafinish-disks was compared to polishing with aluminium oxide disks (AOD). SEM evaluation of the occlusal surface of extracted teeth revealed that diamond polishing pastes or Diafinish-disks produced smoother surfaces than AOD. The pastes, however, damaged the bonding resin. It is recommended to use AOD and diamond polishing systems for the approximal surfaces of the inlays extraorally. Intraorally AOD or Diafinish-disks are recommended. PMID- 2269081 TI - [Diagnostic methods in restorative dentistry--clinical aids]. AB - Diagnostic methods in restorative dentistry are still based on history taking and clinical examinations. Clinical findings, however, reflect only processes in the microscopic range. The correlation of macroscopic symptoms and histological findings is indispensable. In dentistry, and especially in restorative dentistry, too, laboratory findings will assume more and more importance as already is the case in periodontology and cardiology. PMID- 2269082 TI - [The role of x-ray films in diagnosis in operative dentistry]. AB - In operative dentistry x-ray films play an important part as a diagnostic procedure. Image quality depends on factors such as exposure and projection but also on optimum processing of the x-ray film. Of particular importance among the exposure-related factors are such features as variable voltage, short exposure time and narrow focussing. According to the new regulations in Germany x-rays may be used if this is indicated for medical reasons in dentistry. This condition is given far more frequently than x-rays are performed in the dental office. In the diagnosis of caries individual bitewing radiographs, if indicated, should always be preferred over panoramic radiographs. In pulp diseases radiographs may aid in detecting chronic pulpitis and in differential diagnosis with apical periodontitis. Both for diagnosis and documentation on intraoral films, tooth fractures are best imaged using two different projections. Radiovisiography facilitates radiographic diagnosis by employing a simple technique and operating with considerably lower doses. PMID- 2269083 TI - [Bonding of air-brushed non-noble metal surfaces]. AB - Frequently, bonded restorations are not inserted into the patients' mouths until a few days after air brushing in the laboratory. By that time the reactive bonds of the metal surface may have undergone saturation by air during storage or by saliva components during try-in. This in turn, might result in a loss of bond strength. According to the present in vitro study it is possible to bond NPM alloy restorations with Panavia Ex several days after air brushing with corundum. The bond strength after up to 150 days of storage in water is approx. 25 N/mm2 and thus clearly above the clinical minimum requirements of 10 N/mm2 (internal enamel strength). After contamination with saliva, restorations must be air brushed again before bonding. PMID- 2269084 TI - [Stress profile during curing contraction of composite resin adhesives]. AB - The wall-to-wall curing contraction of thin composite resin layers was recorded with a tensometer. The composite resin was applied to cylindrically shaped ceramic sample holders with diameters of 3 mm, 4 mm and 8 mm. The distances of the sample holders was set at 50 microns, 100 microns, 150 microns, 200 microns and 300 microns. The shrinkage stress recordings clearly show that the shrinkage forces are governed by the distance of the sample holders and not by the volume or the configuration factor of the composite resin layers. PMID- 2269085 TI - [Severe hard tooth structure decay following full body radiotherapy prior to bone marrow transplantation]. AB - A case of severe hard tooth structure decay in a patient aged 31 following bone marrow transplantation is presented. So far tooth decay of such severity was only found in connection with radiotherapies for oral and maxillofacial malignomas. Scanning electron micrographs of 4 extracted teeth reveal different degrees of enamel and dentine decay. Major areas of exposed dentine, particularly at the buccal and incisal surfaces where the enamel has broken off in splinters, show massive growth of bacteria. The dentinoenamel junction is also extensively involved. Implications for dental care of bone marrow transplant patients during and after treatment are being discussed. PMID- 2269086 TI - [Middle course between group and individual preventive programs]. AB - A pilot study was initiated to prove the effectivity of a prophylaxis programme for small groups of preschool children. A total number of 190 children was examined twice a year at the Dental School of Erlangen. The dental examination included df-s index and plaque index according to Quigley-Hein. Tooth cleaning was performed in small groups under professional supervision. Professional plaque removal and local fluoridation concluded each session. Twice a year the parents were offered oral hygiene instructions and informed about the relationship between sugar and caries. After two years the dfs-values were significantly lower in the test group than in the control group. Mean dfs scores ranged from 1.9 for the experimental to 3.8 for the control group. These comparatively low recordings -as against other investigations--may be due to the relatively high social standing of the children. PMID- 2269088 TI - [Prophylaxis programs in the dental office--evaluation of a survey of dentists]. AB - Questionnaires on dental prophylaxis were sent to one thousand West German dentists. 457 of them were returned. 61.7% of the dentists interviewed were working in urban, 38.8% in rural areas. The results revealed that the importance of dental prophylaxis is still underestimated today. PMID- 2269089 TI - [Dental and periodontal sequelae of bulimia nervosa]. AB - Twenty-eight women with established bulimia nervosa according to the US psychiatric diagnostic criteria DSM III R with periods of morbidly increased appetite and vomiting, as well as 35 psychically and somatically healthy women were subjected to dental examination. The bulimic patients revealed a significantly poorer dental status (DMFS rate) than the control group. Within the patient group a deterioration of the DMFS rate was observed parallel with an increase in the frequency of vomiting and bulimic attacks, in sugar consumption and duration of the disease, as well as a decrease in salivary flow. Causes and implications for treatment and prevention are discussed. PMID- 2269087 TI - [Physical growth and adult height of orthodontic cleft lip and palate patients]. AB - No unusual variations were found in the skeletal age of 38 female and 78 male patients with clefts of the lip and palate at the time of orthodontic treatment. The patients were divided in groups according to gender and severity of the cleft. In all groups a tendency towards over-average growth was found, which manifested itself rather in adulthood than at the time of orthodontic treatment. The mean height of adult women was 165 cm, 3 cm more than the average values found by Tanner. The mean height of men was 180 cm, i.e. 6 cm more than the corresponding values of Tanner. Only one man showed a body height of less than the third percentile, although he had been within the normal range during orthodontic treatment. Two girls rated below the third percentile during orthodontic treatment, but later grew up to the normal range of height. Hence it may be concluded that dwarfism is not among the factors that must be expected in the orthodontic treatment of cleft lip and palate patients. PMID- 2269090 TI - [Chances for the intraoral use of screen films?]. AB - The development of film/screen combinations has reached a point where they can be used intraorally for many indications. Compared with the fastest non-screen films the dose can be reduced by the factor 8, at the moment. For a wide-spread clinical usage, however, practicable application techniques still have to be developed for the intraoral film/screen combination. PMID- 2269091 TI - [Test of an electronic fissure caries detector]. AB - The reliability of an electronic detector for caries in pits and fissures was tested by means of physical measurements, histological sections and clinical evaluation. The device measures the ohmic resistance of the tooth, technical data are given. First we compared measurements and histological sections of teeth due for extraction. The results indicated a high sensitivity of the device for caries, false positive diagnoses did not occur. Based on this, a clinical evaluation on 179 teeth was performed. Under practical conditions the sensitivity of the electronic detector (0.77) was lower than in the first part of the study; conventional diagnosis revealed more carious lesions in dentine (sensitivity: 0.82). PMID- 2269092 TI - [Vitality tests of the tooth pulp using laser Doppler flowmetry]. AB - Laser-Doppler flowmetry allows a non-invasive assessment of the microcirculation in circumscribed tissue areas. However, measurements in intact human teeth prove to be extensive, as far as instrumental equipment and time requirements are concerned. Therefore we developed an application system which allows us to transfer the principle of measurement under clinical conditions. Thus we were able to prove that the signal recorded can be regarded as a specific expression of pulpal microcirculation. A comparison between vital teeth and root-filled teeth shows that the signal to noise ratio is sufficiently high to allow a definite assessment of pulp vitality. PMID- 2269093 TI - [Evaluation of the new radiovisiography system]. AB - The latest version of the Radiovisiography-system was evaluated in comparison to its predecessor and a high speed periapical film (Agfa Dentus M4). Both RVG systems proved to have the same sensitivity and are capable of displaying a similar contrast range. Nevertheless additional functions of the new system allow a much better visualisation of the radiographed structure. Compared with Dentus M4 periapical films the RVG-System provides less sensitivity but a wider range of contrast. PMID- 2269094 TI - [In vivo study of variously concentrated fluoride gels in the surface enamel]. AB - The efficacy of differently concentrated aminofluorides was determined under in vivo conditions. Enamel samples of human teeth were attached with a composite buccal surfaces of upper molars in 21 test persons and treated for 3 min with a 1.25% respectively, 0.4% aminofluoride gel. After 4 weeks in the oral cavity, during which no fluoride-containing dentifrices were used, the fluoride content of all enamel samples decreased. The results show, that the gel containing 0.4% fluoride was statistically less effective than the 1.25% gel. Intraoral factors seem to have more influence on the degree of demineralization than the fluoride content. PMID- 2269095 TI - [Electrophoretic analysis of potential receptors for oral streptococci in human saliva]. AB - Initial adhesion of oral streptococci occurs at specific binding sites present in the dental pellicle. These receptors are salivary proteins and glycoproteins which by necessity possess affinity to dental enamel as well as to the adhering microorganism. By gel electrophoresis and immunoblotting, five such proteins were shown which bound to hydroxyapatite and oral streptococci. Information on the molecular events of initial adhesion to dental surfaces by oral microorganisms may possibly open new avenues in caries prevention. PMID- 2269097 TI - [The problem of tooth hypersensitivity following the placement of acid-etch retained inlays]. AB - Placement of 225 resin or ceramic inlays using the acid etch technique resulted in post-operative pain of the tooth in 16.1% of the cases. The hypersensitivity decreased in most cases within 4 to 8 weeks, 8 inlays had to be removed. Teeth with bases of phosphate cement showed similar results as those with glass ionomer cement. Possible reasons for post-operative hypersensitivity include etching the base, polymerization shrinkage and marginal gaps and, first of all, etching the dentin. PMID- 2269096 TI - [Pulp toxicity of luting cements]. AB - With the aid of laser-Doppler-flowmetry we are able to determine changes in the microcirculation of the tooth pulp. This method can also be used for testing the histocompatibility of dental materials. The zinkoxiphosphate cement Tenet and the glass ionomer cement Ketac-Cem are examined for tissue tolerance. This is done by determining the incisal and apical changes in pulpal microcirculation. Tenet has almost no discernible effect on pulpal microcirculation. Ketac-Cem causes a longlasting hyperaemia in half of the cases which seems to depend on the depth of cavity preparation. PMID- 2269098 TI - [Failure-time analysis of extensive amalgam restorations]. AB - Statistical methods of survival-analysis were applied to investigate the "life time" of three types of class II amalgam restorations: 1355 F3-, 355 F4-amalgam filling, 108 TMS-pin-retained extensive amalgam restorations and 222 single crowns of a total of 630 patients of a private dental office. After 8 years of service about 50% of the extensive amalgam fillings, but 12% of the single crowns were still under risk. PMID- 2269099 TI - [Comparative SEM study of root canals prepared with Intraendokopf 3-LDSY and 3 LD]. AB - A total of 211 root canals were prepared in extracted teeth using either hand instruments or two engine-driven instruments (KaVo Intraendokopf 3-LDSY and 3 LD). The teeth were investigated by light and scanning electron microscopy. The best results in terms of smoothing the canal wall were observed in the teeth prepared with hand instruments. The Intraendokopf 3-LD was found to be useful in supporting manual methods in certain limited cases, such as curved narrow canals which are hard to access. 3-LDSY, however, proved to be less efficient because it tended to bind in the canal so that the full working length could not be reached. PMID- 2269100 TI - [Root canal therapy--clinical results]. AB - Clinical and radiographic evaluations of root canal therapy indicated, that after correct patient selection endodontic therapy is technically feasible in most cases (even in posterior teeth). Only in few cases (3%) did symptoms of flare ups (5.4-13.4%) last for more than one week. This rate could be further reduced by additional measures, such as the local application of antibiotics and steroids. Long-term success rates for root canal therapy have been reported to range between 71 and 96%. The patient's age and the type of tooth affected had no effect on prognosis. Teeth with periapical resorptions displayed slightly lower success rates. Failures were primarily attributable to overfilling or inadequate instrumentation and/or filling. Root canal therapy should be part of an overall treatment plan including considerations of primary and secondary prevention as well as each patient's individual needs. PMID- 2269101 TI - [Laser Biostimulation in dentistry]. PMID- 2269102 TI - [Studies on the accuracy of fit of non-precious metal posts and cores]. AB - When cemented, directly and indirectly fabricated posts and cores should have good retentive properties and passive fit. Both features require adequate accuracy of fit. The results published in this paper demonstrate that, when using the NPM alloy Dentitan, this is requirement is met only by the direct fabrication method. Without subsequent fine adaptation the mean width of the marginal openings was 87 microns as against 248 microns in indirectly fabricated posts. The interactions in the area of the real interfaces between stump and posts and their effects on the cervical margin are discussed. PMID- 2269103 TI - [Development of plaque-induced gingival pockets in an animal experiment]. AB - Single teeth and resected jaw specimens including periodontal tissue were prepared as saw-cut thin-ground specimens without previous decalcification. The specimens were classified into 4 stages of pathogenesis to allow studies into the mechanisms of gingival pocket formation. Examination of the preparations under the light microscope indicated that the pathologic gingival pockets caused by microbial plaque might be formed by degenerative alterations in the second or third innermost cell layer of the junctional epithelium. The intercellular contacts were dissolved and, thus, cyst-like cavities were formed within the epithelium. The contact between tooth enamel/cementum--basal membrane--epithelial cells, however, was maintained. Artifacts could be ruled out by comparing preparations of single teeth with those of entire jaw segments. PMID- 2269104 TI - [Hypodontia with anlage of all four third molars]. AB - Orthopantomographic films and anamnestic data of 1553 orthodontic patients presenting four third molars were evaluated for tooth agenesis. Agenesis was found in 94 patients (6.1%). There were no significant differences between male and female patients. The most commonly missing teeth were the lower second premolars followed by the upper lateral incisors and the upper second premolars in decreasing order of frequency. Compared with the data in the literature, these results suggest that agenesis occurs less frequently in patients with anlage of all four third molars. PMID- 2269105 TI - [Adding to the diagnostic possibilities of MR tomography of the TMJ]. AB - 54 patients with arthrogenous dysfunctions were examined by means of MR tomography. Imaging of the position and shape of the intraarticular soft tissues was achieved in 64 out of the 67 TMJs examined. The results give rise to the expectation that MR tomography can be further developed to provide a reliable diagnostic tool not only for detecting dislocations in the sagittal plane, but also for imaging mediolateral alterations in the disk position, disk perforations and restrictions in the physiologic mobility of the articular disk. PMID- 2269106 TI - [Geometric basis for temporomandibular joint localization]. PMID- 2269107 TI - [Precision of the Cerec-System: the milling unit]. AB - The Cerec-System is a computer-assisted method for fabrication of customized ceramic inlays. Until now there are no data available to judge the precision of this system, which is a function of several variables. This study investigated the tolerance of the milling unit by using computer-constructed data sets for test purposes. REM pictures show how the diamond bur is affected by several milling cycles. Overall precision along the x- or z-axis is largely independent of the inherent properties of the milling instrument used, such as wear. Precision along the y-coordinate, however, is dependent on the number of milling cycles and the feed along the horizontal axis. Best results can be obtained by using a new bur and slow feed. PMID- 2269108 TI - [Leucrose metabolism in the microflora of the oral cavity]. AB - The metabolizing activity towards leucrose in comparison to sucrose and sorbitol in human saliva and plaque-borne microorganisms was assessed using the Warburg technique. Leucrose metabolism was slightly increased initially, but the overall rate and total amount of leucrose degraded was lower than that of sorbitol. This suggests that the cariogenic potential of leucrose, if there is any at all, is very low. PMID- 2269109 TI - [Inhibition of caries by Na-saccharin]. AB - The inhibition of dental caries by Na-saccharin was studied in an optimized and standardized experiment with cara rats. The animals were given a cariogenic diet ad libitum as well as under controlled frequency feeding conditions. The addition of 0.5% Na-saccharin to the cariogenic diet produced no cariostatic effects. Ancilliary microbiological in vitro and in vivo experiments showed no appreciable bacteriostatic effects on the cariogenic bacteria flora. PMID- 2269110 TI - [Sorption and solution in autopolymerizing and light-cured composite materials]. AB - When stored in water, polymeric filing materials with similar components but different activation systems exhibited similar tendencies in terms of sorption and solution behavior. After 7 days of storage, the uptake of water ranged between 12.1 and 58.9 micrograms mm-3. Solubility varied from 0.3 to 44.3 micrograms mm-3. Within the observation period the surface hardness of the 12 different test and reference materials was increasing. The polymerization of the photosensitive materials was considerably affected by the type of light source used. PMID- 2269111 TI - [Occlusal margin quality of Cerec-inlays several months after insertion]. AB - The quality of the occlusal margins of 58 computer-machined ceramic inlays (Cerec) was examined by SEM. The adhesion of the luting composite to enamel and to the inlay appeared more of less stable. However, the wear of the composites was substantial and more pronounced in Brilliant and in Microfill pontic C than it was in Heliomolar. PMID- 2269113 TI - [Marginal seal of cervical composite inlays in vitro]. AB - The presence of microleakage at the dentinal margins of conventional Class V restorations and direct composite inlays in combination with four dentin bonding agents was assessed by means of dye penetration. The use of dentinal adhesives with conventional one-step composite fillings failed to prevent marginal leakage. The dentin bonding agents used in this study were for more efficient when used with direct composite inlays. The resistance to thermal stress of these bonded Class V composite inlays was improved by application of a secondary light and heat cure, probably due to relaxation of residual material stress. PMID- 2269112 TI - [Clinical comparison of different cervical fillings after one year]. AB - Cervical lesions in 38 patients were restored using composite resins (n = 57), the "sandwich-technique" (n = 64) or glassionomercement (n = 66). Immediately following insertion and 4, 8, and 12 months later, the restorations were examined clinically and in the SEM. Two composite fillings and one filling each of the two other types of restoration were lost. After one year the quality of the dentinal margins of the composite restorations was statistically (p less than 0.05) inferior to the two other methods. Margin quality in enamel was rated superior (p less than 0.05) with glassionomercement as against the other materials. Clinically, the composite filling yielded poorer results regarding marginal integrity and discoloration, although in general they showed superior esthetics. In restoring cervical lesions the use of glassionomercements or the "sandwich technique" has definite advantages over composite fillings. For the evaluation of new restorative materials and techniques, SEM should be used in addition to clinical examinations. PMID- 2269115 TI - [Computer-assisted technologies in dentistry]. AB - The introduction and production of the Cerec-System was the first time, when a method of computer-aided design and manufacturing (CAD/CAM) of dental restorations moves to the chairside. New technologies like optical impression, solid modelling of crown shapes by CAD-Programs or computer controlled milling were acquired from the field of industrial production. Nevertheless, the Cerec Systems is indicated only in a limited range of clinical situations, and the production of a well fitting computer-designed full crown is not yet possible at this stage of development. It can only be guessed whether these advancements will be achieved in the near future. PMID- 2269114 TI - [Studies of the bond of two different types of composites to etched enamel]. AB - The strength of the bond between a microfilled or, respectively, a hybride composite and acid-etched enamel was examined in a shear test and by SEM in human teeth after different modes of preparation. The results showed that the best bond strengths were obtained with microfilled resin without use of a bonding agent. The retention of the hybride composite was better in combination with a bonding agent. Mechanical reduction of the enamel increased the bond strengths of all tested materials. PMID- 2269116 TI - [Psychology of dental home care]. AB - The results of the present study are based on a two-step approach: explorative psychological pilot study (n = 100) international survey of a so-called representative cross-section of the population of the Federal Republic of Germany (n = 100), France (n = 517) and Spain (n = 514). The main results to be noted are: In all three countries the frequency and the duration of toothbrushing are still showing deficiencies. This applies above all to men in general and to not gainfully employed German women in particular. Quality and intensity of dental home care increase with the extent of personal hygiene consciousness in the private, professional and public spheres, with an increased body consciousness, with the increasing knowledge of health and hygiene, with the rising standards of the personal behavior related to preventive measures, body, household underwear and environmental hygiene as well as with the scope of a monitoring style of education for cleanliness based on the behavioral rules conveyed by parents to their children. PMID- 2269117 TI - [Clinical results of partial denture anchorage using extracoronal bonded attachments]. AB - 16 caries-free partially edentulous patients were treated with 36 extracoronal adhesive attachments to support 4 removable partial dentures in the upper and 14 in the lower jaw. The cast nonprecious metal retainers were electrochemically etched and bonded with Superbond to the prepared abutment teeth. No debonding of the retainer occurred during the incorporation time of maximal 52 and minimal 3 months. PMID- 2269118 TI - [Analysis of the life of ceramometallic veneers on cast palladium base alloy bridges (Bond-on 4)]. AB - 186 cast palladium base alloy bridges (Bond-on 4) with ceramometallic veneers have been followed up for 3 years. During this period about 10% ceramic defects have been observed. PMID- 2269119 TI - [SEM study of failures in acid etched cast prosthodontics]. AB - Eight bonded prosthodontic units (mean wearing time 14 months), with 7 retainers spontaneously debonded during clinical use and 9 retainers removed by the dentist, have been studied by SEM. Since only bond fractures at the acrylic/metal interface and mixed fractures could be detected, it may be concluded that late failure is governed by processes at the interface between metal and acrylic. The lost retainers showed overgrowth of mainly rod-shaped bacteria, although one of the artificially removed retainers that was clinically stable beforehand, also exhibited bacterial overgrowth. This suggests that sequential debonding is possible; hence bonded retainers impart a longterm caries risk to abutment teeth. PMID- 2269120 TI - [Studies on the elastic deformation of skeleton palatal plates]. AB - The elastic behavior of various types of Kennedy Class II/1 skeleton palatal plates with transversal connectors of varying widths has been the subject of this study. During function a permanent deformation is not to be expected. Theoretical considerations give rise to the assumption that the support axis is not the border between load-carrying and unloaded maxillary areas. This border is rather shifted towards a bounded saddle situation due to the deformation of the major and minor connectors depending on the forces of mastication and the shape of the plate. Relieving the denture base is not necessary to avoid rocking. Increasing the rigidity of the denture base results in a reduction of the loads placed on the saddle on the one hand, and in an increase in the forces of draw at the counterlateral bounded saddle on the other, which may cause dislodging of the entire denture. PMID- 2269121 TI - [Reproducibility of surface roughness in vivo using elastomers, compounds and the replica technique]. AB - A direct profilometric evaluation of impression materials, particularly elastic materials, has not been possible up to now. The optical fine scanner RM 600 Laser Stylus (Rodenstock) allows touch-free scanning of surfaces, thus providing a direct quantitative assessment of impressions made with elastic materials. To determine the suitability of various impression materials and methods for direct profilometric analyses, the accuracy of reproduction was verified by comparing the surface structures of elastomer and compound impressions as well as replicas with the original. With two exceptions in the replicas, the mean roughness values (Rz) obtained showed no significant differences. This result suggests that the materials used are suitable for direct profilometric evaluation. PMID- 2269122 TI - [Assessment of tooth pulp reaction to dental materials in an animal experiment]. AB - Laser Doppler flowmetry is a useful method for quantifying changes in microcirculation. The present study is designed to clarify if this method may also be used to assess the biocompatibility of dental materials. The experiments carried out on rats' incisors have shown that it is possible to record circulatory reactions occurring in the direct vicinity of the site of application. The reactive change in microcirculation in the apical part clearly differs from the local reaction at the site of application. A modification of the experimental set up allows the synchronous recording of blood flow in the apical and the incisal parts of the pulp. Calcium hydroxide is used to illustrate the local and the overall circulatory reaction of the dental pulp. PMID- 2269124 TI - [Reproducibility of hinge axis localization by stereognathography]. AB - The program of the Stereognathograph V for localization of the hinge axis has been experimentally verified. Auxiliary recording devices have been mounted on an articulator and the process of localization has been simulated. On an average, the joint axis can be located in the articulator with an accuracy of 0.6 mm. In individual cases, errors may be up to 1.5 mm. PMID- 2269123 TI - [TMJ morphology after condylar dislocation fractures in childhood]. AB - In a CT- and NMR-study, condylar remodeling after conservative treatment of condylar dislocation fractures in growing individuals was evaluated. The regenerated condyles displayed great similarities. Two condylar parts could be differentiated--one with and one without muscular attachment. The medial part represents the former small fragment and the lateral part a bony outgrowth. One of the patients studied demonstrated a bifid condyle. NMR-records were remarkable in that each of the three patients presented a lateral pterygoid muscle with the two heads oriented one above the other rather than side by side. This does not seem to support the observation made in experiments, that the disc remains fixed to the caput in low condylar fractures. PMID- 2269125 TI - [Studies on pain suppression by means of transcutaneous electric nerve stimulation (TENS)]. AB - TENS is used in many fields of medicine to provide safe and effective pain relief, yet the application of this technique to dentistry remains almost unexplored. In this study the effects of TENS at various stimulation frequencies on pulpal sensitivity to electrical vitality testing and to cavity preparation were investigated. Pulpal sensitivity to electric vitality testing was reduced by approximately 14% after TENS, with no significant differences between individual stimulation frequencies. During cavity preparation, TENS eliminated or minimised pain in approximately 67% of treatments, the best results being obtained under TENS at 99 Hz (the highest frequency investigated). Patients preferred high frequency TENS because of the accompanying sensations of warmth and relaxation. PMID- 2269126 TI - [Gingiva pigmentation in PFM and amalgam restorations]. AB - A 27-year-old white female patient, claiming her psychiatric disorder to stem from a mercury intoxication caused by amalgam restorations, was examined. Circumscribed gingival pigmentations were found around PM crowns cemented on amalgam fillings. The histologic and metallographic examination of the incisional biopsy sample of the pigmented lesion together with the toxicological results revealed no indication of a mercury intoxication. In order to enable corrosive reactions to proceed as slowly as possible PM crowns should not be in contact with amalgam fillings, as this case showed. PMID- 2269127 TI - [Prevalence of root caries in a healthy adult population]. AB - An epidemiological study involving 963 subjects aged 25 to 64 years revealed at least one carious and/or filled root surface in 40.2% of all females and in 42.7% of all males. The number of teeth and tooth surfaces affected by root caries increases continuously with age. In relation to the total number of teeth, males display a higher prevalence of root caries than females, with the exception of men aged between 55 and 64. High-risk susceptibility shows no correlation with age, although there are more surfaces at risk in males. Independent of the sex, root caries prevalence is highest in the molars and premolars of the mandible and in the canine of the maxilla; lower incisors are the teeth with the least caries involvement. Labial root surfaces are most frequently affected by caries in the mandible; the prevalence rate is twice as high in males than females. The lingual surfaces of maxillary molars of females and the proximal and buccal surfaces of incisors of males are the most frequently affected tooth surfaces. PMID- 2269128 TI - [In vitro studies on the acidifying effect of liquid baby food on dental plaque as compared with breast and cow's milk]. AB - Early caries of the first dentition is generally caused by the misuse of liquid baby food. It was the aim of this study to compare the cariogenic potential of commercial baby foods with that of breast and cow's milk. The cariogenicity was assessed by measuring the decrease in the pH of human plaque material. For this purpose, 140 plaque pH curve graphs were obtained with the aid of the earlier described oral cavity simulator. The acid production observed with the commercial baby foods examined was highly significantly greater than with breast or cow's milk. However, there was no statistically secured difference between the commercial products with different lactose contents. Cow's milk resulted in a lesser decrease in plaque pH than breast milk. PMID- 2269129 TI - [Crown and restoration margins]. AB - The marginal quality of a crown or a filling is of great importance for the success or failure of any restoration. Secondary caries and a marginal periodontal disease are the result of defects in this very critical area. This should be mainly caused by a plaque accumulation, which is determined by the adaptation, the contour, the placement and the quality of the surface of the restoration margin. With respect to the irritation of the marginal periodontium specific cytotoxic effects of each material might be a cofactor too. PMID- 2269130 TI - [Dysmorphophobia in dentistry]. AB - Patients suffering from dysmorphophobia with symptoms involving the masticatory system, i. e. teeth, mouth and jaws, were subjected to comprehensive examinations in close cooperation with the psychiatric profession. In rare cases the problem underlying the urgent desire for treatment in difficult patients is a disease known as dysmorphophobia. The signs of this disease that become evident in the dental office and the specific personality features of the patients affected are described and demonstrated in three typical case reports. Our experience has shown that irreversible and isolated dental manipulations are to be avoided. An interdisciplinary treatment objective (besser: approach?) integrating dental treatment into a greater therapeutic context is proposed. PMID- 2269131 TI - [Quality of the marginal seal of spark-eroded crowns using different modes of preparation]. AB - Six acrylic tooth stumps were prepared for an evaluation of the marginal quality of crowns produced by spark erosion. Four different methods were used for preparation of the crown margins. Each stump had two different margin preparations. The crowns were fabricated with the aid of spark erosion. Serrated sections were then made for an analysis of marginal defects. The results have shown that the mean size of marginal openings is highly dependent on the preparation method used. PMID- 2269132 TI - [Periotest method for the quantitative assessment of occlusal loads]. AB - Using a serial periotest unit we determined the periotest values for disclusion, slight centric occlusion, maximum intercuspation and axially in 102 subjects with a total of 1769 teeth in periodontally healthy dentitions. All teeth were grouped according to the criteria presence or lack of antagonist contact in maximum intercuspation, excentric abrasion facets and occlusal restorations, and statistically evaluated. The difference-normal range for physiologic occlusal loads can be assessed by comparative periotest measurements in disclusion and maximum intercuspation. Thus we have, for the first time, a quantitative, objectifiable parameter for the assessment of the "dimension of occlusion", which at the same time provides information on the functional load on the periodontia of antagonists. Premolar teeth with occlusal restorations tended to have significantly greater differences in the periotest values than teeth with natural occlusal surfaces. By comparing these values with the normal range of differences in the periotest value, a high degree of precision can be achieved in adjusting occlusal restorations. Axial measurements revealed a markedly higher shock absorbing capacity of the periodontia than horizontal measurements. PMID- 2269133 TI - [Evaluation of the hemostyptic properties of a collagen preparation]. AB - In vitro tests were carried out to determine whether the haemostyptic properties of a collagen monomer were lost during the manufacturing process. An increased recalcification time and thromboplastin time as well as failure of the thrombocytes to adhere to the collagen fibres were observed. This indicates that blood coagulation can be attributed only to mechanical irritation of the blood corpuscles and not to the properties of the collagen molecules. PMID- 2269134 TI - [Remodeling after condylar dislocation fractures in growing individuals]. AB - A longitudinal study of the remodelling process in three growing individuals who had suffered low condylar fractures with luxation was made utilizing computerized tomography. The small fragment of the condyle is partially resorbed during the remodeling process, while new bone is formed on the lateral aspect. Below the fracture site in the ascending ramus bone apposition was observed. Each of these remodeling responses was more vigorous in the one child examined than in the two adolescents. PMID- 2269135 TI - [Clinical long-term results with bonded bridges]. AB - 788 patients with 3-unit resin-bonded bridges were followed up over a time period of up to 5 years after placement. In this multicenter study, the following clinical variables were analyzed: caries, periodontal disease, loss of pulp vitality and the behavior of the dental materials involved were assessed. Adverse findings were rare. More data are needed over a longer period of time to support the present results. PMID- 2269136 TI - [Intensive aftercare for patients with removable dentures. Results after four years]. AB - This four-year longitudinal study shows that a recall interval of three months for patients with partial dentures is promising and useful. However, the considerable time and staff requirements for intensive aftercare involves major practical difficulties. PMID- 2269137 TI - [Cyclosporine-induced gingival hyperplasia in renal transplant patients]. AB - Cyclosporine-induced gingival hyperplasia was investigated in a clinical study of 80 renal transplant patients. 34% of the patients exhibited at least mild gingival hyperplasia in the anterior, and 9% presented this finding also in the posterior region. No direct correlation was found between the oral dose or the whole blood concentration of cyclosporine and the presence of gingival overgrowth. Young and female patients were at a significantly greater risk of developing cyclosporine-induced gingival hyperplasia than the other patients. The presence of dental plaque or gingival inflammation was not found to be related to the incidence of gingival hyperplasia. PMID- 2269138 TI - [Benefits and limits of sonography of the masseter muscle]. AB - A sonographic method for diagnosis, follow-up and quantification of normal and hypertrophied masseter muscles is presented. This technique lends itself to diagnosis of macroscopic structural alterations of the muscle as well as tumors in the vicinity. Functional or microscopic tissue changes like trigger points in myofacial pain-dysfunction syndrome cannot be detected sonographically. PMID- 2269139 TI - [Digital image processing in endodontics]. AB - Digital image processing methods were applied to improve the analysis of endodontic follow-up radiographs. After the individual radiographs had been digitized with a videocamera, different standard image processing procedures, such as histogram-equilisation, histogram-matching and noise reduction were performed. In some cases the use of those techniques facilitated the comparison of radiographs taken at long intervals under nonstandardized conditions. As a result, diagnosis of the development of periapical lesions or hard tissue formation in teeth with incomplete root formation was improved. PMID- 2269140 TI - [Caries in the deciduous dentitions of kindergarten children in two cities of the Ennepe-Ruhr district]. AB - The prevalence of caries of deciduous teeth was studied in a survey of 2688 children, aged between 3 and 6 years, from kindergartens in the cities of Witten and Hattingen in the Ennepe-Ruhr district. The DMF/T index of the three-, four-, five- and six-year-old children in Witten was 1.7, 2.5, 3.1 and 3.7, respectively. In Hattingen the DMF/T index recorded was correspondingly: 1.1, 2.9, 2.6 and 3.1. The proportion of naturally healthy dentitions of 57.1% in three-year-old children is decreasing to 29.6% in six-year-old children in Witten and from 67.6% in three-year-old children to 36.6% in six-year-old children in Hattingen. Compared with a study from 1978, caries prevalence has generally dropped by 20% in three- to six-year-old children in Witten. Judged by the criteria established by the WHO, the documented caries prevalence is still very high in both cities. PMID- 2269141 TI - [Clinical and instrumental examination of tongue motor function]. AB - The examination of tongue motor functions requires a clinical examination of voluntary movements as well an objective evaluation of the intraoral movements during speech, deglutition, mastication and during rest. For a comparison with the simple visual assessment of voluntary movements with the mouth opened, intraoral tongue movements have been studied using various techniques. The use of lateral x-ray palatography and electromagnetic articulography (EMA) for objective intraoral measurement of tongue motor activitiesis described. Case examples are given for simultaneous recording of midsagittal movements of the tongue, the mandible and the velum during swallowing and speaking. PMID- 2269142 TI - [Linearity and error correction of the Meyer/dal Ri hinge axis measurement system]. AB - Measurement errors inherently related to the instrument and those due to external factors were analysed for the SAS hinge axis measurement system in conjunction with the digital recording system. An optical bench served as measurement apparatus. Linearity errors are substantially less than 0.1 mm and thus of no clinical relevance. A slight reduction in the size of the movement coordinates imaged with slight incongruences of the six measurement canals results from erroneous calibration. The recording system proves to be insusceptible to interference by external factors in practical application. The projection error correction we investigated experimentally was satisfactory. Merely the processing quality of the electrical wiring attached to the measuring foils was not fully satisfactory. PMID- 2269143 TI - [Biomechanically optimized construction of occlusal splints and subjective evaluation by probands]. AB - In a double blind study twelve class I probands received occlusal splints with six different customized anterior guidances. The subjective feelings were rated using a psychologic scale. It was shown, that splints with a large "a" were better rated than splints with a small "a". "a" is the radius of the maximal curvature of the sagittal anterior tooth curvature. The transition between positive and negative ratings was very sharp and localized at the individual "a". These results suggest that occlusal splints can be optimized by including customized anterior guidances. A detailed technical description of the manufacturing of these splints is given. PMID- 2269144 TI - [Logic and myth of tooth morphology]. AB - Measuring 32 selected maxillary dental casts in all dimensions with the aid of a laser scanner, we obtained 3-dimensional coordinates in a standardized coordinate system. Vertical-sagittal cuts were simulated to extract data of the protrusive curvatures. In this way, the original measuring data were available for analysis. It was the purpose of this study to verify two statements of Kubein-Meesenburg's theory. One is that all protrusive curvatures of one individual are identical, the other that there is an individual-specific parameter a which, when inserted in the equation of the katenate, yields a description of these identical protrusive curvatures. Two different methods of approximation were designed, one optical/graphic method, the other according to strict mathematical criteria of analysis. Both provided different results. In interpreting this discrepancy of results, we found that the reason is associated with the way of handling the so called third dimension, a sum of mathematical criteria that is necessarily involved in approximating the curvatures. Based on strictly mathematical modes of analysis we feel compelled to deny the identity of the protrusive curvatures in any one individual and the existence of the proposed individual-specific parameter a. PMID- 2269145 TI - [Anterior tooth curvatures, tooth size and arch form]. AB - In this study a possible relation between the morphological outline of the palatal concavity of upper incisors and that of the corresponding arch form was analysed. Our results showed that these two parameters seem to be independent variables of the masticatory system. PMID- 2269146 TI - [Morphology of the laterotrusive paths in dentitions with normal function]. AB - The occlusal surface of the posterior teeth of 20 subjects with class-I-occlusion were analysed by means of an electronic profilograph in laterotrusion. Each of the curvatures recorded was defined by an approximated radius as well as its angle to the occlusal plane. The software used was specifically developed to suit this particular purpose. The data showed characteristic regularities. The results indicate that the average radius of the canine is longer than that of the molars. An alternating increasing and decreasing tendency of the angles to the occlusal plane was observed. The results suggest that the concept of canine-protected occlusion may be strengthened by the fact that there is a genetic determination of the canine dominance. PMID- 2269147 TI - [Comparative studies of measuring methods for the six-dimensional recording of spatial mandibular movements]. AB - A catalog of criteria has been developed for testing and judging methods to record extensive movements of the mandible. The aim is to find a method that functions in all six dimensions (translation and rotation) and precludes system errors. Two methods that seem to be in principle able to fulfil the criteria have been tested with calibration sets. The catalog, the results of the survey and developments to improve these methods are presented. PMID- 2269148 TI - [Masticatory pattern of patients with TMJ clicking]. AB - 36 patients with clicking of the TMJ during chewing were examined to determine the influence of clicking sounds on masticatory performance. Electrognathographic measurements of chewing movements in the sagittal plane were compared with the electronic records of clicking sounds. Four characteristic features of chewing movements associated with the incidence of clicking sounds could be identified. PMID- 2269149 TI - [Diagnosis and treatment of compression joints]. AB - A clear-cut diagnosis of "compression joint" is usually difficult in daily practice. The two main reasons for this seem to be a lack in specific diagnostic examination procedures and of an unambiguous nomenclature. The results of the treatment of 148 patients and those of a long term study on 50 patients with "compressed joints" provided us with a foundation for establishing a specific method of examination which might be very useful in diagnosis and therapy of the "compression joint". PMID- 2269150 TI - [Cardinal criteria for TMJ assessment in sagittal magnetic resonance imaging]. AB - In diagnosis and therapy of temporomandibular joint disorders magnetic resonance imaging is an ideal method for visualizing hard and soft tissue structures of the temporo-mandibular joint in a short examination. In this paper we present the main criteria used in interpretating magnetic resonance images and explain these criteria in patient cases. PMID- 2269151 TI - [Biomechanic principles of the sagittal compensating curve]. AB - The alignment of the buccal teeth along the compensating curve is of functional importance. It is closely related with the functional gear system of anterior and posterior guidance. Measurements have shown that individual differences between masticatory systems are mainly attributable to functional parameters. Purely skeletal parameters are of comparatively little variability. The compensating curve may be regarded as a guiding element within a master gear systems which includes the gear system of anterior and posterior guidance. PMID- 2269152 TI - [Myofunction in players of wind instruments]. AB - Within the framework of a longitudinal study, tongue function was examined for maximum pressure, force/time ratio and motility with the aid of a force, pressure and impulse transducer in 181 pupils playing wind instruments and 120 control persons. The methods designed for this purpose provided a reproduction of tongue performance during the act of blowing a wind instrument. The results of this study show statistically significant differences between persons who play wind instruments and those who do not and players of other types of instruments. The data derived from these results permit statements about the degree of muscular malfunction among players of wind instruments. Furthermore, they are helpful in the assessment of therapeutic success or failure. PMID- 2269153 TI - [Retrusive joint function and stability range of the mandible]. AB - In CO the mandible possesses a retrusive function, although this is hardly visible to the naked eye. Yet this function is equal in importance with the protrusive function for the mechanical stability of the mandible in CO while muscular forces are acting. It is theoretically concluded and empirically demonstrated herein that any force, whose line of action is within a certain area of stability, acts to secure the mandible in CO. The limits and range of this area as well as its clinical implications are discussed. PMID- 2269154 TI - [Comparison of two computer-aided recording systems: MT 1602 and Compugnath]. AB - Two computer-aided jaw movement recording systems were compared with each other. The results showed that both systems work satisfactorily for use in reconstructive dentistry and TMJ diagnosis. It is, however, emphasized, that there are a number of shortcomings which may have a negative effect on the recordings. PMID- 2269155 TI - [Embryologic studies on the development of tooth form]. AB - 3-dimensional reconstructions were made from serial sections of human embryos in order to trace back the development of the anlagen of the deciduous dentition. It could be shown that in the stage the late cap/early bell back contours of the inner enamel epithelium resemble the outlines of the later completed tooth. It is discussed that the shape of the earlier stages may set the preconditions for the further formation processes resulting in the occlusal morphology. PMID- 2269157 TI - [Properties of a measuring system for digital occlusion diagnosis]. AB - The properties of a new digital technique of demonstrating and quantifying occlusal contacts (T-scan) were tested in vitro the sensor foil used was 95 microns in thickness and had approx. 1350 measuring points. When a given force was applied at the same point on one foil several times in sequence, the readings were highly reproducible. Applying the same force at different points on the same foil and at points on different foils, however, failed to bring about reproducible results. The reasons for this lack of reproducibility and possible modifications are discussed. PMID- 2269156 TI - [Differential diagnosis of reciprocal joint clicking using electronic axiography (SAS)]. AB - 25 patients with reciprocal clicking in one or both temporomandibular joints were examined clinically and with an electronic axiographic system (SAS-System). Studying the direction of the sudden change of the condylar path during clicking, we established a tentative differential diagnosis of "centric anterior dislocations" of the disc and "eccentric posterior dislocations". Interpreting the axiographic pathways we found an eccentric posterior dislocation of the disc in 20 TMJs. But in at least 11 cases, which could be re-evaluated by magnetic resonance tomography (CMR), the diagnosis "eccentric posterior dislocation" was false. As we found several variations of anterior dislocations with a cranial and lateral deviation of the condylar path during opening clicking, the diagnosis of "eccentric disc dislocations" established by axiography was not reliable. PMID- 2269159 TI - [A new ultrasound system for recording masticatory function in implant patients]. AB - Chewing patterns were measured in patients with unilateral osseointegrated oral implant bridges. An intraindividual comparison was made between the implant treated and the conventionally treated side. Measurements were made with a newly developed device operating on the principles of ultrasonics. A motor stepper driven simulator (jaw replicator) was connected to investigate the occlusion during the terminal masticatory movements. No significant differences were found between the implant and the control side. PMID- 2269158 TI - [Functional status of patients prior to and after orthognathic surgery]. AB - The functional status of 12 patients was evaluated before and after orthognathic surgery for a malocclusion. The results of surgical intervention showed distinctive differences in the status of the temporomandibular joint and masticatory musculature. The number of tender muscles on palpation and the occurrence of temporomandibular joint sounds was reduced to approximately one third. However, the number of joints showing pain on palpation increased. Axiographical recordings of movement paths shawed normal values in 2 patients postoperatively. Chewing patterns were generally more harmonious, but the size of the chewing field was smaller. PMID- 2269160 TI - [Clinical study on rheumatoid arthritis of the TMJ]. AB - 256 individuals with inflammatory rheumatic diseases and 117 individuals of two control groups returned their questionnaires in a survey of subjective symptoms of the masticatory system. Subjective symptoms of the temporomandibular joint (tmj) were reported by 41% of the patients with rheumatoid arthritis, 29% of the patients with psoriatic arthritis, 20% of the patients with ankylosing spondylitis and 23% of the patients with other rheumatic diseases (such as Reiter's syndrome). Statistically significant differences (p less than 0.05) regarding the occurrence of "difficulties in opening the mouth wide" and "crepitus from the tmj" were found between the various types of rheumatic arthritis. In 40 patients with rheumatic diseases and tmj-symptoms the tmj was examined clinically, by orthopantomography and lateral tomography. Radiographic abnormalities were found in 68% of the patients and classified by a new radiographic index, according to the index of Steinbrocker. There were no indications for a relationship between a loss of posterior support and extensive radiographic changes of the tmj. The most common objective symptoms were pain on chewing, crepitus in the tmj and tenderness to palpation of the masticatory muscles and neck. PMID- 2269161 TI - [Intraoral condyle-related positioning of the maxilla in Le Fort 1 osteotomies]. AB - A new technique for positioning control in Le Fort I osteotomies is presented. This intraoral procedure allows three-dimensional positioning of the condyles in the desired centric or therapeutic relation and of the maxilla at the same time. It combines the intraoperative use of the "Condylar Positioning Appliance" with the "3D Doublesplint Method". PMID- 2269162 TI - [Axiographic irregularities in patients with different clinical function statuses]. AB - A group (n = 20) of young, clinically symptom-free subjects (Helkimo Di = 0) was compared with a group (n = 22) of TMJ-patients (Di greater than 2) regarding the frequency and the amount of axiographic findings of malfunction. 5 different mandibular movements were monitored using the SAS-system with tenfold magnification in 2 planes of recording. An analysis of these results showed significant effects in several parameters. According to these findings the highest reliability to detect functionals differences is at the maximum distance between the ex- and incursive tooth-guided protrusive path in the sagittal vertical plane. Although other parameters showed only slight discrepancies, a cautious interpretation of axiographic tracings must be recommended. PMID- 2269163 TI - [Three-dimensional dynamic imaging of TMJ movements using stereognathography]. AB - Conventional imaging methods showing only one joint side are insufficient diagnostic tools for analyzing pathologic condyle paths. Although they demonstrate the effects of internal joint derangement, they fail to reveal the pathologic causes. Superior results are obtained by means of computer-assisted evaluation programs which allow simultaneous imaging of both joints in perspective. PMID- 2269164 TI - [Relationship between transversal joint guidance and buccal curve morphology]. AB - The relationship between the morphology of the curvature of laterotrusion facets and tooth-guided tracings of the mediotrusive condyle path was studied in 20 probands with normal function. The varying inclinations of the dominant laterotrusion facets in cuspid-protected or group-guided occlusion has no bearing on the angle of the mediotrusive paths relative to the horizontal plane. The morphology of the buccal curve allows no predictions as to the direction of the mediotrusive path curvature. Only the movements of the idling condyle were influenced by the type of occlusal guidance. In lateral excursive movements of the mandible with the teeth in contact group-guidance frequently resulted in an upward movement of the laterotrusive condyle and thus to a compression of the intraarticular soft tissues. Although valid conclusions regarding any type of interdependence are impossible unless we are able to measure real tooth and joint movements simultaneously, the results of our study contradict other hypotheses at any rate. PMID- 2269165 TI - [Video arthroscopy in diagnosis and treatment of TMJ disorders]. AB - Video arthroscopy using the double puncture method was applied in 32 patients with disc dislocations, disc perforations, rheumatoid arthritis and varying joint disorders of unidentified etiology. In disc dislocation cases the alterations observed in the superior joint cavity correlated well with the preoperative diagnosis, whereas minor and lateral disc perforations escaped detection by arthroscopy, possibly due to technical problems. Based on a critical assessment of this method, arthroscopic operative techniques are being developed for disc dislocations and hypermobility disorders, possibly even for chronic arthritis and related conditions. PMID- 2269166 TI - [Biocompatibility of dental materials: Part 2. Materials with mucosal contact]. AB - Dental materials which are supposed to contact the oral, mucous membranes during their intended dental use may affect our patients health in different ways. Their local and systemic toxicity, and their allergenic and tumorigenic potential are reviewed and methods of biocompatibility testing discussed. Special emphasis is placed on impression materials, denture base resins and dental alloys. PMID- 2269167 TI - [Reactions of the oral mucosa to mechanical load stimuli from dentures]. AB - The oral mucosa is the primary medium bearing removable dentures. Problems of adaptation and incompatibility of denture bases borne by mucosal tissues first of all arise at the mucosa covering the palate and the alveolar ridges. Depending on its functional qualities, the denture bearing mucosa more or less fulfills the task of buffering chewing forces acting on the denture base and distributing them on the bone surface. Studies on physiological and morphological reactions of the denture bearing tissues resulting from mechanical stresses show that the mucosa is entirely capable of tolerating short-term pressures during chewing. In this connection the increase in the thickness of the denture bearing mucosa must be considered as a physiological response to mechanical load. PMID- 2269168 TI - [In vitro growth of periodontal ligament fibroblasts between bone and root slices]. AB - In a first experiment the proliferation and growth kinetics of periodontal ligament fibroblast monolayers generated from human healthy (HPDL) and diseased (DPDL) periodontia were compared. In a second experimental series a periodontal ligament-like space was developed by laying a root slice inside a bony ring slice on the bottom of a tissue culture petri dish and leaving a space of about 0.5 mm between both structures. HPDL cells showed a higher proliferation rate than DPDL cells. Growing into the space between the slices, the PDL cells built up a matrix which was composed of cells and fibrils. HPDL cells built up the matrix more rapidly than DPDL cells. PMID- 2269169 TI - [Acoustic feedback for probing at constant force]. AB - Probing of the gingival crevice is generally recognized as the most important diagnostic procedure in periodontitis. Reliable measurements are only possible by probing at constant force. A freshly isolated porcine mandible was used to test, if acoustic feedback enhances the reliability of probing. Our results indicate that the feedback significantly reduces the total probing force and also the variance between single measurements. PMID- 2269170 TI - [Periodontal treatment of furcally involved teeth: with or without root resection?]. AB - A retrospective radiographical and clinical evaluation of 275 molars (59 patients) with different classes of furcation involvement was assessed. Flap operations with and without root resections had been performed and the patients were enrolled in a regular maintenance program for at least 4 years (up to 8 years). The life expectancy of molars with root resection was compared to molars conventionally treated by flap operation. Probing depth was reduced significantly on molars of the lower jaw even with class III involvement, progression of periodontal disease could be arrested. The progression of bone loss (mean 1.4 mm) in molars of the upper jaw with a class III involvement could be stopped only by root resection. During the observation period 12 teeth had to be extracted. 8 for nonperiodontal reasons. The long-term prognosis of class III furcations only treated by flap operation with or without tunnel preparations was as good as that of root resected molars. PMID- 2269171 TI - [Guided bone tissue regeneration--a clinical and histological pilot study]. AB - The aim of the present investigation was to study whether a technique based on the principle of guided tissue regeneration is able to generate new osseous tissue around osseointegrated implants in humans. 14 titanium implants (IMZ) were inserted in 4 patients. The fixtures were modified by hydroxyapatite (HA) or titanium discs measuring 3 mm in height, which were screwed onto the implants. The modified implants were inserted in such way, that the discs were above the level of the alveolar bone. 3 modalities of treatment were performed. In group I HA granules were placed on the bone around the disc-implant-constructions and completely covered by an ePTFE membrane in order to create a space for ingrowth of bone-derived cells. In group II the membrane alone was placed and in the control group HA granules alone were used. After complete closure of the flap and 2-4 months of healing, the membranes including the generated tissue and the discs were removed and processed for histological examination. Clinical results demonstrated that in group I hard tissue had formed underneath the membrane, which strongly adhered to alveolar bone. Histological examination revealed new formation of trabecular bone. When the membrane alone was used, the created space was almost completely reduced during healing and no significant tissue formation had occurred. The greatest clinical problem was flap dehiscence over the membrane. In the control group the HA granules and discs were encapsulated in connective tissue. Limited by the small number of sites, the study indicates that a membrane technique according to the principle of guided tissue regeneration promotes new bone formation around osseointegrated implants in humans. PMID- 2269172 TI - [Concentrations of A. actinomycetemcomitans in subgingival plaque following short term minocycline therapy]. AB - In the present study we examined alterations in the proportions of cultivable flora of A. actinomycetemcomitans (A.a.) in subgingival plaque of 25 patients with different forms of periodontitis, 7 days after systemic administration of 200 mg/d Minocycline-HCl. Remarkable shifts in the flora were apparent. Sites with low or extremely low initial levels of A.a. (less than 10%) showed an increase in mean proportions from 2.7% to 15.7% (p less than 0.01). A.a. was eliminated in only 18% of sites after 1 week of minocycline therapy. Subgingival scaling resulted in 80% of sites without detectable A.a. However, if present, the organism accounted for 51% of the cultivable microflora, on average. Our data emphasize the importance of a sufficiently extended period of antibiotic therapy and efficient mechanical debridement of all tooth surfaces to eliminate the organism. PMID- 2269173 TI - [Importance of oral hygiene in the treatment of capillary hemangioma of the gingiva]. AB - This is a case report on two patients, 21 resp. 25 years old, who suffered from recurrent capillary hemangioma of the gingiva. Prior to surgical therapy the hygienic conditions were improved in several sessions with professional preventive treatment and oral hygiene instructions. Post-surgical treatment consisted of efficient plaque control and adequate three-monthly oral prophylaxis sessions. In both cases the hemangioma was not observed to recur up to 2 1/2 resp. 1 1/2 years later. PMID- 2269174 TI - [Dental sac and its role in periodontal development]. AB - The present study examined the role of the innermost layer of dental sac tissue in periodontal development. Empty bony crypts were filled with Hydroxylapatite ceramic granules of porous consistency in 5-day-old rats. After 4.5 and 24 weeks the specimens were processed for light and transmission electron microscopy. Only 4 weeks later cement regeneration was seen on ceramic surfaces with bundles of oriented collagen fibers inserting in the cementoid matrix. Ultrastructurally the newly formed cementum-like tissue was in intimate contact to the synthetic hydroxylapatite crystals. A consistent finding was the presence of an interface between cementum and the ceramic surface. The present findings question the unique role of the "investing layer" in periodontal development and the existence of cement-inducting properties of dentin. PMID- 2269175 TI - [Results of mechanical stresses from removable dentures on ridge mucosa and bone]. AB - 247 human cadaver jaws (obtained from 115 complete denture-wearers, 98 partial denture-wearers, 34 control persons) were examined histopathologically to determine if there is a correlation between tissue response and type of prosthetic management. The pathohistological changes of tissue and bone were evaluated statistically according to sex, age and topography of maxilla and mandible. The highest number of pathological findings was associated with those complete dentures and partial dentures where the biomechanical principles of construction had not been observed. Age, sex and topography, however, do not reveal any significant influence on tissue and bone. PMID- 2269176 TI - [Dissolution of alloy components from Ni/Cr base alloys by bacterial leaching]. AB - The method of bacterial leaching of non precious dental alloys represents a useful completion of the method arsenal of biological investigations. In contrast to other well known methods it allows to point out small differences in corrosion resistance between alloys of the same type in a biologic system. PMID- 2269177 TI - [Studies on the allergenic potential of palladium alloys]. AB - Epicutaneous tests with test solutions of the European standard series and palladium chloride (1%) were performed in 486 patients of the University Hospital for Dermatology in Aachen. 17.9% of the patients exhibited Ni, 8.6% Co, 7.4% Pd and 4.1% Cr allergy. In 18 of 36 patients with a positive patch test reaction a further epicutaneous and epimucosal testing with metallic plates of pure palladium and a palladium alloy was performed. In 34 cases a positive skin reaction to palladium chloride was combined with a positive skin reaction to nickel sulphate. Only in one case was it possible to demonstrate an allergic reaction to a palladium metallic plate, which was tested additionally in artificial saliva. The results show that a dental alloy envisaged for use should be tested in an epicutaneous test, if the patient shows a positive reaction to the metallic salt solution. In case of positive patch tests to nickel sulphate, dental palladium alloys should not be used as an alternative unless sensitivity to palladium has been tested. PMID- 2269178 TI - [Plaque accumulation on various veneering resins--a clinical study]. AB - Initial plaque accumulation on five veneering resins was investigated to determine differences in vitality and adhesion of microorganisms. After 24 hours of exposure of the specimens in the mouth, the vitality of the bacteria was reduced. The vitality and the adhesion increased only a little until the fourth day. The high plaque accumulation observed in vivo on resin veneers seems to depend primarily on the degeneration and mechanical lesions of the surface after a certain time in mouth. PMID- 2269179 TI - [In-vivo corrosion tests of dental alloys in relationship to saliva pH]. AB - The corrosion of four dental alloys and titanium was studied in relationship to saliva pH and plaque accumulation in vivo. Test specimens were scanned for porosities with an image analysis system before and after exposure to the oral milieu. The saliva pH was monitored during the study period. After four days of exposure in the mouth the plaque accumulation and the vitality of the plaque on the alloy surfaces was evaluated. Plaque accumulation and mean saliva-pH were not correlated with the observed surface corrosion. The least surface effects were observed on titanium, which showed the highest plaque accumulation. Different alloys showed different bacteriostatic effects. The least amount of living bacteria was found on titanium. Plaque accumulation and bacteria vitality depended on material and test person. PMID- 2269180 TI - [Testing the solubility of dental alloys]. AB - Solubility of dental non-precious alloys was investigated. In the first few days of immersion high concentrations of dissolved metal ions were observed. For some alloys the rates increased, for others they decreased with time, when the immersion bath was replaced by a freshly prepared one. Solubility increased slightly when metal surfaces were ground with emery-paper, grain size 1200, which was intended to simulate the disturbance of the passivation layer by mastication. Porcelain firing, however, caused largely increased rates, depending on the kind of alloy. The results are to be taken into consideration when formulating standards for corrosion resistance tests. PMID- 2269181 TI - [Solubility of nickel from dental alloys in saliva]. AB - Dental students in the clinical courses of prosthodontics manufactured maxillary cast partial dentures from 6 nickel-containing alloys according to set guidelines. Prior to insertion as well as up to 7 days after insertion resting saliva samples were collected and analyzed for their nickel contents with the aid of atomic absorption spectrometry (AAS) using a graphite tube. 20 min after insertion the salivary nickel levels were above the blank value. After 3 h the salivary nickel levels were as half as high compared to values of 20 min. After 7 days for most alloys they decreased to the starting values again. PMID- 2269182 TI - [Clinical application of powder metallurgically produced crowns]. AB - The clinical applicability of a newly developed powder metalurgic procedure (Degusint/Degussa) for the production of crowns and bridges is evaluated in a controlled clinical study. Until now 366 units ranging from occlusal inlays to four-unit ceramometallic bridges were incorporated. In a total of 15,000 marginal gap measurements, medians of 22 microns (Degusint G) and 26 microns (Degusint U) were found, with 95.4% or 94.0% respectively of the values ranging below 70 microns. The PFM-process increases the marginal gap from median 27 microns to 33 microns. With uniform pore distribution mean values from 90.3% to 92.4% of the theoretical density were reached using the available powder compositions. Compared with cast fixed prostheses no differences in intraoral behaviour could be noticed up to now. PMID- 2269183 TI - [Measuring the accuracy of various elastomeric impression materials using a CNC coordinate measuring device (Part 1)]. AB - This study compares the accuracy of 23 impression materials. With each material seven impressions of a stainless steel master die were taken under standardized conditions. Characteristical dimensions of the master die and of the stone dies as well were determined by means of a CNC coordinate measuring device. Differences in prepared tooth heights ranged between -36 and +19 microns. The occlusal distances between prepared teeth were 2 to 54 microns greater on the stone dies than on the master die. Diameters differed by -89 to +52 microns. The two phase impressions tended to result in stone dies of reduced size, whereas single phase and double mix impression techniques produced larger stone dies than the master die. PMID- 2269184 TI - [Optimizing the bond between metal and bonding agent in bonded restorations using a simplified silicoating procedure]. AB - The tensile bond strengths of five different resinbonding-systems to a Co-Cr alloy (Dentitan) are tested. The samples were stored in artificial saliva (37 degrees C) up to 150 days and thermocycled (5 degrees-55 degrees C, 18,750 cycles). In contrast to micromechanical bonding-systems, mechanical-chemical ones showed no significant changes in tensile bonding strength during this observation period. The tribochemical silicoating procedure (Rocatec) seems to be suitable for Co-Cr-alloys used in resin-bonded restorations. PMID- 2269185 TI - [Chemical and thermal compatibility of all-ceramic systems]. AB - The chemical and thermal compatibility of the all-ceramic systems Vitadur-N, Hi Ceram and In-Ceram as well as the combinations of Dicor with Vitadur-N, Dicor with NBK 1000 and Dicor with Vivodent, respectively, were investigated by means of electronmicroscopy and microprobe measurements at the interface of each compound, and thermomechanical analyses of the components were performed. The results show good contact at the interface of all combinations investigated. No evidence was found for diffusion at the interface except in the In-Ceram system, were a migration of K+ from Vitadur-N dentine into the glassy phase of In-Ceram occurs. The thermomechanical analyses showed a good thermal compatibility of all compounds investigated. PMID- 2269186 TI - [Quantitative analysis of the corrosion rates of palladium alloys by isolated polarization]. AB - The corrosion resistance of three palladium alloys and one conventional high noble alloy were examined by isolated polarization. Using this method, isolated plots of the cathodic and anodic reaction can be recorded. The corrosion current is given as the anodic and cathodic plots intercept. The current densities of the palladium alloys were approximately ten times higher than of the high noble alloy. All results were dependent on the acidity of the electrolyte. PMID- 2269187 TI - [Comparative material testing of dental impression and articulation plasters according to German Industrial Standard DIN 13911]. AB - The purpose of the present investigation was a comparison of three special articulation plasters and three impression plasters. As DIN 13911 does not refer to articulation plasters, the inspection as well as the testing of pouring time, setting time, setting expansion and compressive strength using standard and manufacturer's consistence as carried out conforming to the guidelines for impression plasters. None of the tested plasters could meet the requirements of inspection in all points. Considering the physical parameters all plasters are up to standard, while Alpa quickstone and Arti-Plaster exhibited very low expansion and high compressive strength values. Although the compressive strength standard needs redefining, the value of a standardized testing technique for dental plasters is evident. PMID- 2269188 TI - [New frontiers in the prosthodontic management of patients with loss of all or most of their teeth]. AB - In view of the increasing life expectancy and the growing number of older people, the conservation of denture bearing tissue will become an essential task in the treatment of edentulous patients. According to a clinical survey it could be proved that about 60% of the female and 40% of the male complete denture wearers had a high degree of bone loss of the lower jaw. The standard factors of function are described, particularly emphasizing the importance of muscular denture stabilization, jaw relation and mode of occlusion. The conservation of remaining single-posted teeth is necessary, not only for psychical reasons, but also with regard to support and function of the dentures. The biomechanical principles of design and approved denture constructions are illustrated. In order to ensure long-term denture function and care for the bearing tissue, it is mandatory that excellent oral hygiene, proper denture care, and periodical recalls, at intervals of 1 year at most, be maintained. PMID- 2269189 TI - [Studies on the mobility of soft tissue marks of the lower face]. AB - The mobility of soft tissue points used for measuring the rest vertical dimension was assessed in 29 probands with full dentitions and 24 edentulous subjects. A video-aided procedure was used for recording the measuring pictures. Similar results were obtained with fully dentulous and edentulous subjects. For the upper jaw the point of the nose was the mark undergoing the least fluctuations, due to the action of the mimic muscles. For the lower jaw the least mobile skin area was between the labiomental sulcus and the gnathion. PMID- 2269190 TI - [Crown fractures in removable dentures]. AB - Crown fractures following prosthodontic treatment with tapered crowns were studied in a group of 209 controlled cases after a wearing period of 36 months. Out of a total of 841 abutment teeth 29 fractured. There was no correlation between the number of abutments and the risk of crown fracture. Incisors and canines were affected to the same extent as premolars. 27 teeth could be saved by post retention. PMID- 2269191 TI - [Assessment of the acceptance of modern periodontal treatment]. AB - In a retrospective study we assessed the acceptance of necessary modern periodontal treatment by more than 2200 patients in the years 1981-1987. 50% of the patients withdrew from treatment in the presurgical phase and 42% in the postsurgical maintenance phase; particularly during the first year the drop out rate was high (64%). One of the reasons could be a certain lack of health awareness and fading willingness of the patients for permanent cooperation as known from longstanding chronic diseases in general medicine. Therefore it remains necessary to enhance periodontal health awareness and to promote information on the cause and treatment of periodontitis and the subsequent maintenance care. PMID- 2269192 TI - [Mechanical properties of collagen or gelatine-stabilized blood clots]. AB - Mechanical properties of blood clots stabilized with collagen (Pentapharm) and a gelatine (Gelastypt-M) sponge were compared with the help of thrombelastography and volumetric tests. The collagen songe was distinctly inferior to gelatine in stabilizing the clot against retraction. It appears that gelatine is a better material for filling large osseous defects that are subjected to mechanical stress. PMID- 2269193 TI - [Comparative study of the Interplak tooth cleansing instrument]. AB - Unlike manual and electric toothbrushes, the brush head of the Interplak instruments remains stationary while ten tufts of bristle rotate. The efficacy of this new system was evaluated in comparison to a conventional electric toothbrush (Braun dental d3). When used for the first time the Interplak instrument proved to be more effective in reducing plaque. After training periods of 2 and 4 weeks there was, however, no significant difference between products. PMID- 2269194 TI - [Methods and materials for the construction of complete dentures]. AB - In a survey the methods and materials used for making complete dentures were collected from 603 dentists. The impression material most frequently used for primary impressions was alginate and elastic impression material for functional impressions. Compared with an earlier survey the percentage of dentist using needle point tracing for recording jaw relations increased from 6 to 40%. Remounting complete dentures was done by 64% of the dentists whenever required; 9% applied this method as a routine. PMID- 2269195 TI - [Effect of clenching forces on the results of needle point tracing in the sagittal plane]. AB - It was the purpose of this study to assess the influence of the applied clenching force and the positioning of the needle in the sagittal plane on the results of needle point tracings. The results show a direct influence of the applied force, whereas the influence of the position of the needle point showed great interindividual variations. PMID- 2269196 TI - [Changes in overjet with cuspless complete dentures]. AB - Overjet was measured three times in 46 edentulous patients treated with complete dentures with cuspless teeth: 3 to 5 days after insertion of the new dentures, after 4 weeks and after 10 months. Despite the lack of cusps for fixing the occlusion we found only little overjet reduction. PMID- 2269197 TI - [Studies on canine guidance in complete dentures]. AB - The effect of canine guidance with guiding angles of 70, 55 and 30 degrees in relation to the median sagittal plane and balanced occlusion on the kinetics of upper complete dentures was investigated both in an in-vitro-experiment and in patients. It appeared that canine-guided dentures led to considerable dislocations during tooth-guided lateral movements, whereas balanced occlusion caused only minor movements, which were always directed toward the alveolar ridge. PMID- 2269198 TI - [Biometric studies on implanted and natural abutments]. AB - The mobility of 50 osseointegrated implants, inserted for improvement of the support of dentures in edentulous lower jaws, was studied during a period of up to 3 years by means of mechano-electronic measurements. The results showed that 3 months after implantation osseointegrated implants have less quasi-static mobility than natural teeth without periodontal lesions. Under the stresses of mastication the mobility of osseointegrated implants continuously increases. After 2-3 years, implants show a similar mobility as natural teeth supporting comparable denture constructions. The Periotest readings of implants were significantly lower than those of natural teeth, largely independent of the date of mobility measurement. A prognosis of functional properties as well as predicting the impending loss of osseointegrated implants is possible with the aid of long-term mobility measurements. PMID- 2269199 TI - [Functional parameters and occlusion of partial dentures as a function of the type of attachment]. AB - Patients with mandibular removable partial free-end dentures were monitored for two years. Functional and occlusal parameters were evaluated for a possible association with the type of attachment. Signs and symptoms of clinical functional disturbances were found to be independent of the type of attachment. In cases with tapered or telescopic crowns occlusal stability was maintained longer than in cases with clasps. PMID- 2269200 TI - [Prognosis of abutment teeth in severely reduced residual dentitions]. AB - The survival rate of 2094 abutment teeth in 671 removable partial denture cases was analysed. Within an interval of 2-7 years 150 abutments were lost. The survival-rate of abutments in severely reduced dentitions differs significantly from that in dentitions with more than 3 teeth. Regarding the framework design there was no significant difference in the survival-rate of abutment teeth for removable partial dentures supported by more than 3 teeth. PMID- 2269201 TI - [Periodontal and caries prevention in patients with open maxillary defects following tumor surgery]. AB - Patients with jaw defects resulting from tumors often have partially edentulous dentitions, because of the tumor surgery and, in most cases, advanced age. This dentition, however, can be preserved for many years and utilized in prosthodontic treatment if the principles of caries and periodontal prevention are carefully observed throughout therapy. Premature loss of teeth can only be avoided, if the prosthodontist sees the patient before surgery and before irradiation, so that the necessary measures can be taken in time. PMID- 2269202 TI - [Dermatologic effects of two facial prosthesis materials in combination with glues]. AB - Erythema is frequently observed in the region of contact between facial prostheses and the skin. In a large-scale study on the cutaneous tolerance of facial prosthesis materials, two prosthetic materials (glue and the solvent for the glue) were tested in the allergy test after Magnusson and Kligman (OECD). Only the solvent showed a moderately pronounced allergenic potential in the macroscopic assessment. PMID- 2269204 TI - [Electronic measurements of the masticatory muscles. 2: Interpretation of activity changes in the masticatory muscles]. AB - In part II, a method is described which reduced the variations of the three determinants of the voltage/tension curves to the fluctuation of only one three dimensional variable. A way to estimate three dimensional regions for the fluctuations is shown. For a given level of significance, limits can be calculated that allow us to decide whether differences between post- and pre treatment measurements are random or due to treatment. PMID- 2269203 TI - [Electronic measurements of the masticatory muscles. 1: Methods of recording]. AB - The application of surface electromyography as an aid in diagnosing craniomandibular dysfunction requires that pathological or treatment-induced changes of the EMG be distinguished with sufficient probability from random variations due to methodological or biological reasons. It was the aim of this study to determine the range of variability of elevator muscle EMG, to find experimental methods for improving reproducibility, and to establish evaluation procedures that allow the recognition of treatment-induced effects in the EMG even in the presence of great random variations. For this we measured the voltage/tension relation of the elevator muscles of 42 persons in the range of 20 to 500 N on up to 20 different days under constant experimental conditions. The majority of measurements revealed a non-linear correlation between EMG activity and resulting force, hence second order polynomials proved to be more appropriate than straight lines for representing the activity/tension correlation. Muscle activity was found to vary randomly from day to day within each individual. These fluctuations appeared as varying axis intersections, initial slopes and curvatures which are the determinants of the voltage/tension curves. In ten selected subjects random fluctuations were significantly higher when electrodes were repositioned by palpation of the muscle belly than with the aid of tattoos. PMID- 2269205 TI - [Studies on the cybernetic aspects of occlusal splint therapy]. AB - This study was focussed on the effects of changes in interocclusal clearance on the activity of oral muscles. Two types of occlusal splints were incorporated in 20 subjects without TMJ-syndrome. Their muscle reactions were recorded electromyographically in the masseter muscle. The results show 5 groups of muscle reaction correlated with the mean postural face height. The changed height of the postural position has a significant influence on the control pattern of the masticatory system. PMID- 2269206 TI - [Special ceramic hard substances as separating agents in cast-on procedures for the construction of precision attachments]. AB - A new direct cast-on technology for the construction of telescopic crowns and precision attachments using non-precious alloys is described. Special ceramic hard substances, such as silicides and borides, are used as separating agents for the casting of the secondary structure. The application of the ceramic layers to the primary crown is accomplished with a chemical vapor deposition method. The layer thickness can be controlled and may range between some hundred nanometres and up to a few micrometres. The attainable gaps between primary and secondary casting range between 1 and 8 microns after separating and finishing. PMID- 2269207 TI - [Pre- and post-eruption effects on the functional morphology of the articulating structures]. AB - Profile traces of latero- and protrusive facets of subjects with class-I occlusion showed characteristic regular patterns in curvature and angle to the occlusal plane. There was no significant correlation between the laterotrusive surface profiles and the corresponding transversal movement of the condyle which was recorded electronically in 3 dimensions. Curvature morphology was plotted as a function of tooth eruption, development of the dental hard tissues, and tooth wear. In conclusion the results were applied to comprehensive occlusal restorations. PMID- 2269208 TI - [Conservative treatment of perforated disks]. AB - Stereognathographic recordings were taken of the mandibular movements of 11 patients who had undergone conservative treatment for unilateral disk perforation. The results showed a significant decrease in the condylar inclination angle of the affected joints. Based on these values the condylar inclinations were increased in a condyle positioning simulator (CPS). This allowed production of individually correct occlusal splints. In all cases studied this splinting therapy eliminated pain and crepitus. PMID- 2269209 TI - [Survey of the dental prosthodontic care provided for residents of Wurzburg old people's homes]. AB - Three hundred and six residents of Wurzburg old people's homes (average age: 81 years) were interviewed and examined with regard to their dentures and need for treatment as well as their oral hygiene. Most of the subjects had removable dentures. Oral symptoms, restricted masticatory ability and difficulties with the dentures were reported by only about one third of the senior citizens, although the caries and periodontopathy morbidity was high and considerable defects were found in the crowns, bridges and dentures. Similarly, the subjects own reports on their oral care regimen was contradicted by the poor oral and denture hygiene observed in fact. Neither was there assistance in oral hygiene from the nursing staff nor systematic professional care. Altogether, there is a great need for dental prosthetic treatment in the subjects of this study. PMID- 2269210 TI - [Pulp toxicity of the acid components of acid-base reaction cements]. AB - Laser-Doppler-flowmetry enables us to assess microcirculatory changes in the tooth pulp. This method can also be used for testing the histocompatibility of dental materials. The acid components of Tenet and Ketac-Cem are examined for tissue tolerance. This is done by assessing the incisal and apical changes in pulpal microcirculation. The phosphoric acid of Tenet causes an almost complete collapse of the incisal microcirculation just a short time after its application. The tartrate of Ketac-Cem causes long-lasting hyperaemia, whereas the acryl maleinate-copolymer has no discernible effects. PMID- 2269211 TI - Microtubule assembly and oscillations induced by flash photolysis of caged-GTP. AB - Microtubule assembly and oscillations have been induced using the rapid liberation of GTP by UV flash photolysis of caged-GTP and monitored by time resolved X-ray scattering. The flash photolysis method of achieving assembly conditions is much faster than the temperature jump method used earlier (msec vs. s range). However, the structural transitions and their rates are similar to those described previously. This means that the rates of the transitions in microtubule assembly observed before are determined by the protein itself, and not by the rate at which assembly conditions are induced. The advantages and limitations of using the photolysis of caged-GTP in microtubule assembly studies are compared with temperature jump methods. Caged-GTP itself reduces the rate of microtubule assembly and oscillations at mM concentrations, consistent with a weak interaction between the nucleotide analogue and the protein. X-rays are capable of slowly liberating GTP and other breakdown products from caged-GTP, even in the absence of UV flash photolysis, thus causing an apparent "X-ray induced" microtubule assembly. This effect depends on the X-ray dose but is independent of the caged-GTP concentrations used here (mM range), suggesting that the breakdown of caged-GTP is caused not by the direct absorption of X-rays by the compound but by another intermediate reaction such as the generation of radicals by the X-rays. PMID- 2269212 TI - Fluoride transmembrane exchange in human erythrocytes measured with 19F NMR magnetization transfer. AB - 19F NMR spectra of sodium fluoride in suspensions of human erythrocytes were seen to yield separate resonances for the F- populations inside and outside the cells. Selective saturation of the magnetization of the intracellular population gave rise to transfer of that saturation to the extracellular population. The extent of magnetization transfer was high and it was blocked by the capnophorin (band 3) anion exchange inhibitor 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). A series of magnetization-inversion transfer experiments was carried out for the range of intracellular fluoride concentrations of 11 mM to 136 mM and analysed using one-dimensional 'overdetermined' exchange analysis. This yielded an estimate of the equilibrium exchange Michaelis constant and maximal velocity of 27 +/- 3 mM and 180 +/- 5 x 10(-16) mol cell-1 s-1, respectively. There was no alteration of exchange flux of fluoride at an intracellular concentration of 49 mM in the presence of 50 mM glucose; thus suggesting no interaction between glucose and anions in capnophorin-mediated exchange of solutes. PMID- 2269213 TI - Statistical analysis of K 2 x 2 tables: a comparative study of estimators/test statistics for association and homogeneity. AB - In order to control for confounding variables, epidemiologists often obtain data in the form of a 2 x 2 table. One variable is usually the disease status, while the other variable represents a dichotomous exposure variable that is suspected of being a risk factor. If a confounding variable is present, the data are often stratified into several 2 x 2 tables. The objectives of the analysis are to test for the association between the suspected risk factor and the disease and to estimate the strength of this relationship. Before estimating a common odds ratio, it is important to check whether the odds ratios are homogeneous. This paper presents the results of a Monte Carlo study that was performed to determine the size and power of a number of tests of association and homogeneity when the data are sparse. We also evaluated the performance of three estimators of the common odds ratio. For the Monte Carlo studies, equal numbers of cases and controls were used in a wide variety of sparse data situations. On the basis of these studies, we recommend the Breslow-Day test for nonsparse data, and the T4 and T5 statistics for sparse data to test for homogeneity. The Mantel-Haenszel test of association is recommended for sparse and nonsparse data sets. With sparse data, none of the odds ratio estimators are entirely satisfactory. PMID- 2269214 TI - A nonparametric method for estimating interaction effect of age and period on mortality. AB - In this paper we introduce a new model and develop an estimation strategy to analyze mortality data. The model we dealt with has the specific structure E[log qij] = mu + alpha i + beta j + rho ij subject to the linear restrictions sigma i alpha i/sigma 2i = sigma j beta j = sigma i pij/sigma 2i = sigma j rho ij = 0 for any i and j; here, qij denotes the mortality for the jth period category and ith age category, mu denotes the overall mean, alpha i denotes the ith age effect in antichronological order, beta j the jth period effect, rho ij the general interaction effect; and sigma 2i is the common error variance of log qij for the ith age group. We propose a combined technique of ANOVA and nonparametric smoothing for estimating these parameters. The methods described are illustrated by mortality data on rectum cancer in Japanese males and females between 1950 1986. PMID- 2269215 TI - Using mortality data to estimate radiation effects on breast cancer incidence. AB - In this paper we combine Japanese data on radiation exposure and cancer mortality with U.S. data on cancer incidence and lethality to estimate the effects of ionizing radiation on cancer incidence. The analysis is based on the mathematical relationship between the mortality rate and the incidence and lethality rates, as well as on statistical models that relate Japanese incidence rates to U.S. incidence rates and radiation risk factors. Our approach assumes that the risk of death from causes other than the cancer does not depend on whether or not the cancer is present, and among individuals with the cancer, the risk of death attributable to the cancer is the same in Japan and the U.S. and is not affected by radiation exposure. In particular, we focus on the incidence of breast cancer in Japanese women and how this incidence is affected by radiation risk factors. The analysis uses Japanese exposure and mortality data from the Radiation Effects Research Foundation study of atomic bomb survivors and U.S. incidence and lethality data from the Surveillance, Epidemiology, and End Results Registry. Even without Japanese incidence data, we obtain reasonable estimates of the incidence of breast cancer in unexposed Japanese women and identify the radiation risk factors that affect this incidence. Our analysis demonstrates that the age at exposure is an important risk factor, but that the incidence of breast cancer is not affected by the city of residence (Nagasaki versus Hiroshima) or the time since exposure. PMID- 2269216 TI - Randomization in cancer clinical trials: permutation test and development of a computer program. AB - When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described. PMID- 2269217 TI - Models for association in bivariate survival data. AB - This paper reviews dependence models for bivariate survival data, classifying them into the four groups: the shock model, the Freund model, the Clayton model, and the mixture model. The paper then concentrates on the mixture model, discussing the testing problem for the equality of marginal distributions under the Weibull type baseline hazard assumption. The new test proposed recently by Fujii is introduced, and its characteristic is studied with respect to the test proposed by Nayak and the sign test by simulation study. PMID- 2269218 TI - Application of log-linear model in inference on karyotypic evolution in chronic myelocytic leukemia. AB - Relationships among additional chromosome abnormalities in chronic myelocytic leukemia (CML) with translocation 9;22 [Philadelphia chromosome (Ph1)-positive CML] were analyzed by log-linear models on 709 karyotypes reported in the literature. Additional abnormalities, such as the gain of chromosome 8 (+8), gain of Philadelphia chromosome (+Ph1), isochromosome of the long arm (q) of chromosome 17 [i(17q)], and the gain of chromosome 19 (+19), were frequently observed. A four-way 2 x 2 x 2 x 2 contingency table was considered with respect to the appearance of these four abnormalities, then the hierarchical log-linear models having at least four main effects were fitted to the observed contingency table. Akaike's information criteria of the models reflected the fitness of the model very well. Parameter estimates of the interaction terms indicated that the combinations of two abnormalities, '+8 and +19', '+Ph1 and +19', and '+8 and i(17q)' were positively associated, while '+Ph1 and i(17q)', and '+19 and i(17q)' were negatively associated. Based on the results of the data analysis, an inference was made on the route of karyotypic evolution in Ph1-positive CML; it statistically supports the hypothesis presented by Heim and Mitelman. PMID- 2269219 TI - A comparative study of two statistical models for the analysis of binary data from longitudinal studies. AB - This study extensively compares two statistical models for the analysis of binary data from longitudinal studies. The first model was proposed by Zeger, Liang, and Self, which was abbreviated as ZLS model and another model was proposed by Origasa. The comparison focuses on both analytical and statistical view-points. The first discusses a type of the models and the second evaluates the effect from model misspecification by stimulation, assuming that the ZLS model is true. PMID- 2269220 TI - Estimation of gene frequency and test for Hardy-Weinberg equilibrium in the HLA system. AB - This paper concerns the testing for Hardy-Weinberg equilibrium and the estimation of gene frequency in the human leukocyte antigens (HLA) system. An extensive simulation study for both testing and estimation is given for investigating the performance of the projection method by Eguchi and Matsuura, which has a closed form, and the method is asymptotically equivalent to the maximum likelihood method. We compare our projection test statistic with the likelihood ratio test and the single degree of freedom chi-square test suggested by Nam and Gart. Actual mean square errors of the projection estimator of gene frequency under the Hardy-Weinberg equilibrium are compared with the maximum likelihood estimator and some other estimators recently discussed by Nam. PMID- 2269221 TI - An index for cancer clustering. AB - This paper generalizes the index for temporal clustering proposed by Tango in two ways: it allows for nonuniform population distributions across the study period and it is applicable to the detection of disease clustering in space where there are variations in population distribution among categories of the confounding factor such as age and sex. Applications are illustrated with 1833 cases of mortality from uterine cancer in the Tokyo metropolitan area during 1978-1982. PMID- 2269222 TI - A model for dose rate and duration of exposure effects in radiation carcinogenesis. AB - Multistage models have been used to describe various features of the incidence of cancer including the shape of the age-incidence curve; the influence of age at, duration of, and time since exposure; and the synergistic effect of exposure to multiple carcinogens. However, the models require from five to seven distinct transformations that must occur in a particular sequence. The lack of experimental support for so many events suggests a simpler model involving only two mutational events with a proliferative advantage for intermediate-stage cells. Neither model easily explains the paradoxical phenomenon that protraction of low linear energy transfer (LET) radiation leads to lower risks per unit of total exposure, whereas the reverse occurs for high-LET radiation. In this paper, a three-stage model is considered that consists of two mutations at homologous sites, either or both of which might be induced by radiation, followed by activation of the transformed oncogene, which is not induced by radiation. Single stranded lesions are potentially repairable, whereas double-stranded lesions may increase the proliferation rate. For low-LET radiation, these two mutations are more likely to occur as the result of independent transversals of a cell by separate quanta of radiation, whereas for high-LET radiation, they are more likely to occur simultaneously as the result of a single particle. The predictions of the model are illustrated for various patterns of exposure and choices of model parameters. Various tests of the proposed model are discussed. PMID- 2269223 TI - The effect of measurement error on the dose-response curve. AB - In epidemiological studies for an environmental risk assessment, doses are often observed with errors. However, they have received little attention in data analysis. This paper studies the effect of measurement errors on the observed dose-response curve. Under the assumptions of the monotone likelihood ratio on errors and a monotone increasing dose-response curve, it is verified that the slope of the observed dose-response curve is likely to be gentler than the true one. The observed variance of responses are not so homogeneous as to be expected under models without errors. The estimation of parameters in a hockey-stick type dose-response curve with a threshold is considered on line of the maximum likelihood method for a functional relationship model. Numerical examples adaptable to the data in a 1986 study of the effect of air pollution that was conducted in Japan are also presented. The proposed model is proved to be suitable to the data in the example cited in this paper. PMID- 2269224 TI - Mode of action and the assessment of chemical hazards in the presence of limited data: use of structure-activity relationships (SAR) under TSCA, Section 5. AB - Section 5 of the Toxic Substances Control Act (TSCA) requires that manufacturers and importers of new chemicals must submit a Premanufacture Notification (PMN) to the U.S. Environmental Protection Agency 90 days before they intend to commence manufacture or import. Certain information such as chemical identity, uses, etc., must be included in the notification. The submission of test data on the new substance, however, is not required, although any available health and environmental information must be provided. Nonetheless, over half of all PMNs submitted to the agency do not contain any test data; because PMN chemicals are new, no test data is generally available in the scientific literature. Given this situation, EPA has had to develop techniques for hazard assessment that can be used in the presence of limited test data. EPA's approach has been termed "structure-activity relationships" (SAR) and involves three major components: the first is critical evaluation and interpretation of available toxicity data on the chemical; the second component involves evaluation of test data available on analogous substances and/or potential metabolites; and the third component involves the use of mathematical expressions for biological activity known as "quantitative structure-activity relationships" (QSARs). At present, the use of QSARs is limited to estimating physical chemical properties, environmental toxicity, and bioconcentration factors. An important overarching element in EPA's approach is the experience and judgment of scientific assessors in interpreting and integrating the available data and information. Examples are provided that illustrate EPA's approach to hazard assessment for PMN chemicals. PMID- 2269225 TI - Cigarette smoking and cancer mortality risk in Japanese men and women--results from reanalysis of the six-prefecture cohort study data. AB - In 1965 a cohort of 265,000 residents of 29 public health districts in six prefectures throughout Japan was established and followed between 1966 and 1981. By using survival analysis based on Poisson regression models adjusted for age, prefecture of residence, and occupation, a statistically significant dose response relationship between cigarette smoking and mortality rate was found for cancers of the liver, pancreas, and lung in both sexes; cancers of the oral cavity, esophagus, stomach, larynx, and bladder in men; and cancer of the uterus in women. The magnitudes of relative risks were only slightly affected by adjustment for prefecture of residence or occupation. Analysis using linear relative risk models revealed that the inclusion of a quadratic term for the amount of daily cigarette consumption in addition to the linear term improved the fit of the model significantly for cancers of the esophagus and stomach in men and cancer of the stomach in women. The sex ratio of gastric cancer mortality was higher among smokers than among nonsmokers. When the follow-up period was divided into four 4-year intervals, it was noted that the relative mortality risk associated with lung cancer among males increased significantly during these time periods. PMID- 2269226 TI - Mechanisms of general anesthesia. AB - Although general anesthetics are often said to be nonspecific agents, it is likely that they act at a much more restricted set of target sites than commonly believed. The traditional view has been that the primary targets are lipid portions of nerve membranes, but recent evidence shows that the effects on lipid bilayers of clinically relevant levels of anesthetics are very small. Effects on most proteins are also small, but there are notable examples of proteins that are extremely sensitive to anesthetics and mimic the pharmacological profile of anesthetic target sites in animals. Such target sites are amphiphilic in nature, having both hydrophobic and polar components. The polar components appear to behave as good hydrogen-bond acceptors but poor hydrogen-bond donors. Although the targets can accept molecules with a wide variety of shapes and chemical groupings, they are unaffected by molecules exceeding a certain size. Overall, the data can be explained by supposing that the primary target sites underlying general anesthesia are amphiphilic pockets of circumscribed dimensions on particularly sensitive proteins in the central nervous system. PMID- 2269227 TI - Rules for distinguishing toxicants that cause type I and type II narcosis syndromes. AB - Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed. PMID- 2269228 TI - Electrophiles and acute toxicity to fish. AB - Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms. PMID- 2269229 TI - Assessment of the propensity for covalent binding of electrophiles to biological substrates. AB - Electrophilic character is associated with the ability of external agents to interact with centers of electron density in biological macromolecules and to cause the interruption or alternation of normal activity. With the observation of site specificity in mutagenic events. Pearson's hard/soft acid-based (HSAB) theory is presented as a useful concept in correlating chemical observations in the absence of detailed direct knowledge of the process. Methods for the evaluation of carbon electrophiles (e.g., carbocation character) as reactants are reviewed as potential physical parameters that could be applied in developing quantitative structure-activity relationships. PMID- 2269230 TI - The metabolic N-oxidation of carcinogenic arylamines in relation to nitrogen charge density and oxidation potential. AB - The N-oxidation of carcinogenic arylamines to form N-hydroxy arylamines has long been regarded as a necessary metabolic step for conversion to proximate carcinogenic derivatives. In contrast, arylamine ring-oxidation has been generally considered to be an important detoxification mechanism. Both enzymatic reactions are carried out in the liver and usually involve the cytochrome P-450 monooxygenases. Studies on the metabolic oxidation of certain arylamines have indicated that the relative charge density on nitrogen versus ring-carbon atoms for a nitrenium/carbenium ion-enzyme intermediate correlates with the relative proportion of N-versus ring-hydroxylated products that are formed. A further examination of this approach now shows that positive charge density on the nitrogen, as estimated by Huckel molecular orbital calculations, is consistent with the formation of N-hydroxy arylamines from aniline, 4-aminoazobenzene, 2 naphthylamine, 4-aminobiphenyl, 2-aminofluorene, and 6-aminochrysene, but not from 1-naphthylamine, 1-aminopyrene, 6-aminobenzo[a]pyrene, or 7 aminobenz[a]anthracene. Since greater positive charge on the arylamine nitrogen implies a greater charge localization during the transition state of the enzyme substrate complex, we envisioned that higher oxidation potentials for arylamines, which might be expected to correlate inversely with the ease of total oxidation, would instead be predictive of the relative extent of N-oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269231 TI - Survival models for familial aggregation of cancer. AB - It has recently been shown that the relative risks of the order of 2 to 4 that are frequently found for cancer among relatives of affected cases are unlikely to be explainable by shared environmental risk factors. Classical methods of epidemiological analysis are not well suited to such analysis because they assume that the outcomes of each individual are independent. Classical methods of genetic analysis, on the other hand, are limited in their handling of environmental factors and variable ages of onset. The recent development of random effects models for survival analysis, however, appears to bridge this gap. Specifically, a proportional hazards model is postulated for the effects of measured covariates and of one or more components of frailty that are unmeasured but assumed to have some common distribution and known covariance structure within each family. From these assumptions, the posterior expectation of the hazard for each individual can be derived, given the covariate value and the observed and expected disease history of the family. These are then treated as known in a standard partial likelihood analysis; this is essentially a form of expectation-maximization algorithm. However, this does not provide a valid estimate of the covariance matrix because it fails to take account of the variability in the estimates of the frailties; an alternative approach using the imputation-posterior algorithm is suggested. This paper describes extensions of this approach to multivariate frailty distributions, modifications for application to pedigree and case-control studies, some simulation results, and applications to studies of breast cancer in twins and of lung cancer in relation to family smoking habits. PMID- 2269232 TI - Predicting public concern regarding toxic substances in the environment. AB - The purpose of this research was to identify the variables that increase concern about the health, environmental contamination, and economic consequences of toxic substances in the environment. A mail survey was sent to a New York State sample, and a 66% response was obtained. Seven indices were developed from specific concerns about toxic substances in the environment including, among others, exposure, health effects, pollution, and economic consequences. Stepwise regression analysis was conducted for each concern index. The results suggest that the number of information sources regarding environmental issues was a strong predictor of concern in nearly all models. Other variables that were repeatedly found to be important contributors to the models were years of education, attitudes about government involvement in private industry, knowledge of epidemiology and the scientific method, and the perceived proximity to sources of potential contamination. Unlike other research, women and mothers of sick children did not make large contributions to the model. PMID- 2269233 TI - Health effects of environmental exposure to cadmium: objectives, design and organization of the Cadmibel Study: a cross-sectional morbidity study carried out in Belgium from 1985 to 1989. AB - Cadmium is a cumulative environmental pollutant. For the general population mainly exposed by the oral route and through tobacco smoke inhalation, the kidney is the critical organ. Belgium is the principal producer of cadmium in Europe, and certain areas of the country are polluted by cadmium mainly because of past emissions from nonferrous industries. Preliminary studies carried out in one polluted area have suggested that environmental pollution might lead to an increased uptake of cadmium by the human body and possibly to health effects. Thus, a large-scale morbidity study has been initiated to assess the validity of this hypothesis. The present paper describes the protocol of this study. Its main objectives are to determine to what extent environmental exposure to cadmium resulting from industrial emissions may lead to accumulation of the metal in the human organism; to establish whether or not environmental exposure may induce renal changes and/or influence blood pressure; and to assess the acceptable internal dose of cadmium for the general population. The study design takes advantage of the fact that biological indicators of exposure, body burden, and early nephrotoxic effects of cadmium are available, which increase the likelihood of detecting a cause-effect relationship. PMID- 2269235 TI - U.S.-Japan joint meeting on the toxicological characterization of environmental chemicals of mutual interest. AB - The paper describes deliberations of a meeting between scientists from the U.S. National Toxicology Program and the National Institute of Hygienic Sciences, Tokyo, Japan. The scientific approaches and experimental processes used by each organization in designing, conducting, and evaluating the short-term and long term toxicity/carcinogenicity of environmental chemicals were evaluated. PMID- 2269234 TI - Iron, radiation, and cancer. AB - Increased iron content of cells and tissue may increase the risk of cancer. In particular, high available iron status may increase the risk of a radiation induced cancer. There are two possible mechanisms for this effect: iron can catalyze the production of oxygen radicals, and it may be a limiting nutrient to the growth and development of a transformed cell in vivo. Given the high available iron content of the western diet and the fact that the world is changing to the western model, it is important to determine if high iron increases the risk of cancer. PMID- 2269238 TI - Statistical problems in epidemiologic studies of the natural history of disease. AB - The development of effective disease prevention and treatment programs depends on an understanding of the natural history of disease. A conceptual framework is presented for disease natural history and consists of an asymptomatic period of disease followed by a period of symptomatic disease. The focus is on epidemiologic studies for identifying risk factors of the onset of asymptomatic disease, for identifying cofactors of progression to symptomatic disease, and for estimating the duration of the asymptomatic period. The strengths and limitations of various epidemiologic study designs and sources of epidemiologic data are considered for characterizing disease natural history. Issues in the interpretation and analysis of natural history parameters of disease estimated from cross-sectional, prevalent cohort, cohort, and matched case-control studies are considered. The issues and analytic methods are illustrated with studies of the acquired immunodeficiency syndrome (AIDS) and cervical cancer. Based on these analytic methods, an estimate of the incubation period distribution of AIDS is given. PMID- 2269237 TI - Family history of cancer and mortality among patients gastrectomized because of benign gastric diseases. AB - A preliminary result from a cohort study on the association of a family history of cancer with mortality is discussed in this paper. Among 2200 patients (1912 males and 288 females) gastrectomized because of benign gastric diseases, 274 male patients, and 40 female patients had a family history of cancer. During 2750 person-years of observation, 22 patients with the family history of cancer were found to be dead and 111 patients without the family history died during 17,527 person-years, giving a relative risk of 1.26 (not significant). We focused on the male subjects that were followed up for more than 10 years; however, the observed/expected ratio of cancer deaths for subjects with a family history of cancer was about four times higher than that for those without family history. Since case-control studies on family history are vulnerable to biased recall and interchangeability of cases, more cohort studies like the present study should be conducted to assess the association of the family history of cancer. PMID- 2269239 TI - Managing clinical research data: software tools for hypothesis exploration. AB - Data representation, data file specification, and the communication of data between software systems are playing increasingly important roles in clinical data management. This paper describes the concept of a self-documenting file that contains annotations or comments that aid visual inspection of the data file. We describe access of data from annotated files and illustrate data analysis with a few examples derived from the UNIX operating environment. Use of annotated files provides the investigator with both a useful representation of the primary data and a repository of comments that describe some of the context surrounding data capture. PMID- 2269236 TI - Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen. AB - Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes. PMID- 2269240 TI - Evaluation of the effectiveness of mass screening for uterine cancer in Japan: the potential years of life lost. AB - To evaluate the effectiveness of mass screening for uterine cancer in Japan, we compared the changes in the age-adjusted rates of potential years of life lost (PYLL) due to uterine cancer between 1969 and 1972 to 1973 through 1977 between the high coverage-rate (intensively screened) areas and the comparable control areas. The percent reduction in the average age-adjusted rate of PYLL due to uterine cancer and the years of life saved per 100,000 females were greater in the high coverage-rate areas than in the control areas. These results suggested that mass screening programs for uterine cancer contribute to saving years of life. PMID- 2269241 TI - Population-based case-control study on cancer screening. AB - Matched case-control studies have recently been used to evaluate the effectiveness of cancer screening. They enable us to estimate the odds ratios of dying of cancer or of getting invasive cancer. The study compares people with various patterns of screening history with those who were not screened. Criteria for eligible cases, controls, and screening histories that are compared as exposures are discussed. The results from a case-control study for evaluating screening for cervical cancer are shown as an example. Also, a study design of a case-control study for evaluating lung cancer screening in Japan is discussed, along with biases and applications of case-control studies in evaluating cancer screening. PMID- 2269242 TI - Use of tumor diameter to estimate the growth kinetics of cancer and sensitivity of screening tests. AB - A statistical method has been developed that is useful for studying the relationship between the growth kinetics of malignant tumors and the detection probability either through symptoms or by screening. Mathematical models that describe the distribution of pathological variables in malignant tumors, detected after various histories of screening, are derived and parameters for detection probabilities and the growth kinetics are then estimated by the maximum likelihood procedure. By this method the probabilities of detection through symptoms as well as by screening can be estimated as functions of pathological variable(s) such as tumor size. The growth rate of tumor can also be estimated from the distribution of pathological variables. The present method was applied to gastric cancer in Japan, where an annual screening program for the disease exists. The detection probability for the indirect X-ray used as the screening test was estimated to be 0.323 x (diameter)2/[1 + 0.323 x (diameter)2]. The doubling time of gastric cancer was estimated to be 2.90 months. PMID- 2269243 TI - On the consequences of model misspecification in logistic regression. AB - Logistic regression models are commonly used to study the association between a binary response variable and an exposure variable. Besides the exposure of interest, other covariates are frequently included in the fitted model in order to control for their effects on outcome. Unfortunately, misspecification of the main exposure variable and the other covariates is not uncommon, and this can adversely affect tests of the association between the exposure and response. We allow the term "misspecification" to cover a broad range of modeling errors including measurement errors, discretizing continuous explanatory variables, and completely excluding covariates from the model. This paper reviews some recent results on the consequences of model misspecification on the large sample properties of likelihood score tests of association between exposure and response. PMID- 2269244 TI - Use of screening tests to assess cancer risk and to estimate the risk of adult T cell leukemia/lymphoma. AB - We developed methods to assess the cancer risks by screening tests. These methods estimate the size of the high risk group adjusted for the characteristics of screening tests and estimate the incidence rates of cancer among the high risk group adjusted for the characteristics of the tests. A method was also developed for selecting the cut-off point of a screening test. Finally, the methods were applied to estimate the risk of the adult T-cell leukemia/lymphoma. PMID- 2269245 TI - Calculating excess lifetime risk in relative risk models. AB - When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate. PMID- 2269246 TI - Confidence intervals for effect parameters common in cancer epidemiology. AB - This paper reviews approximate confidence intervals for some effect parameters common in cancer epidemiology. These methods have computational feasibility and give nearly nominal coverage rates. In the analysis of crude data, the simplest type of epidemiologic analysis, parameters of interest are the odds ratio in case control studies and the rate ratio and difference in cohort studies. These parameters can estimate the instantaneous-incidence-rate ratio and difference that are the most meaningful effect measures in cancer epidemiology. Approximate confidence intervals for these parameters including the classical Cornfield's method are mainly based on efficient scores. When some confounding factors exist, stratified analysis and summary measures for effect parameters are needed. Since the Mantel-Haenszel estimators have been widely used by epidemiologists as summary measures, confidence intervals based on the Mantel-Haenszel estimators are described. The paper also discusses recent developments in these methods. PMID- 2269247 TI - Selenium status and absorption of zinc (65Zn), selenium (75Se) and manganese (54Mn) in patients with short bowel syndrome. AB - Selenium level and activity of glutathione peroxidase in plasma were studied in seven patients with extensive short bowel resection due to Crohn's disease, before and during 27-54 weeks of intake of a vitamin and trace element supplement containing 50 micrograms of selenium as sodium selenite. Initial levels of selenium were normal in all except one of the patients. The supplementation had no or minor effects on plasma selenium levels and glutathione peroxidase activity. The absorption of zinc, manganese and selenium was measured with a radionuclide technique before and/or after the supplementation period in five of the patients. The absorption of zinc and manganese was similar to that observed earlier in healthy subjects, while the absorption of selenium was significantly lower. The results indicate that a higher selenium intake or a different form of selenium is needed in these patients to compensate for the impaired bowel function. PMID- 2269248 TI - Effect of inositol hexaphosphate on retention of zinc and calcium from the human colon. AB - Colonic retention of zinc and calcium was studied after installation during colonoscopy in 11 patients of a solution of 30 mumol zinc, 6.4 mmol calcium and 500 mumol inositol hexaphosphate (phytic acid) labelled with 65Zn and 47Ca. Whole body retention of the radionuclide at day 13 was 1.0 +/- 1.0 per cent (mean +/- s.d.) for zinc and 4.0 +/- 2.9 per cent for calcium. The retention of zinc but not of calcium was lower than observed earlier under similar conditions from a solution not containing phytic acid and indicates formation of an indigestible complex between phytic acid and zinc. Addition of amino acids to the solution in 3 subjects did not seem to affect the retention of zinc and calcium. PMID- 2269249 TI - Relation of pregnancy serum ferritin levels to hemoglobin levels throughout pregnancy. AB - Thirty women were studied for the impact of pregnancy iron status on hemoglobin (Hb) and serum ferritin (Ft) during the course of pregnancy. Blood samples were taken 4 weeks before their last menstrual period, at 8, 12, 16, 20, 24, 28, 32 and 36 weeks of pregnancy, during labor and 1 month after delivery. Two groups were formed based on prepregnancy Ft concentration: with high Ft (Ft greater than or equal to 20 micrograms/l) and with low Ft (Ft less than 20 micrograms/l). In women with high Ft, Hb decreased significantly during the first weeks of pregnancy while Ft increased, followed by a gradual fall as pregnancy progressed. In women with low Ft, Hb increased during the first weeks of pregnancy while Ft remained practically unchanged but very close to 0 microgram/l throughout pregnancy. Our findings suggest that besides the hemodilution characteristic of pregnancy, iron deficiency does develop during this period. The fall in Ft in well-nourished women during the first 30 weeks of pregnancy suggests an increased utilization of iron stores, while for those with already low levels of prepregnancy serum Ft, iron stores are not available for this physiological response. Therefore, iron supplementation should be given to women with reduced iron stores before they start a pregnancy so as to insure sufficient iron deposits to cope with the increased iron requirements during this period. PMID- 2269250 TI - Basal metabolic rate in monozygotic and dizygotic twins. AB - The basal metabolic rate (BMR) was determined in 14 pairs of monozygotic (MZ; 11 females, 3 males) and 12 pairs of dizygotic (DZ; 10 females, 2 males) twins, with mean ages of 22.7 and 26 years. Zygosity was confirmed using DNA fingerprinting. When BMR was expressed as kJ/d, kJ/kg/d and kJ/kg FFM/d significant intra-class correlation coefficients were observed in the MZ twins of 0.82, 0.79 and 0.85, respectively. The DZ twins showed much lower intra-class correlations coefficients of 0.1, 0.07 and -0.04. Although the results of the study suggest a likely genetic component to the variation in BMR, they should be interpreted with caution as heritability estimates vary with the method of calculation. These will be critically discussed in the paper. PMID- 2269251 TI - A whole body transportable indirect calorimeter for human use in the tropics. AB - A transportable, whole body indirect calorimeter, designed for use in the tropics, is described. The calorimeter was built to study energy expenditure of people having chronically or acutely low levels of food intake, and it will help to determine energy adaptations made by individuals with restricted food intake. The calorimeter comprises two units: a 27 m3 ventilated chamber connected to an office housing control and monitoring equipment. The system also allows the experimenter to assess the rate of energy expenditure by means of a ventilated hood or a baby respiration chamber. The incoming air flow rate is variable and is typically set at approximately 30 l/min. Carbon dioxide production (VCO2) and oxygen consumption (VO2) are continuously monitored by means of differential gas analysers via a computerized data acquisition unit. Gas production/consumption rates are measured with a delay of 80 s, the complete response to step changes in VCO2 or VO2 consumption being calculated over 15 min using the rate of change terms in the gas exchange equations. The total electrical power required for the whole system is 12 kW. The calorimeter has been functioning for nearly 4 years in a rural village of The Gambia during which ambient temperatures have ranged from 16 to 44 degrees C and dewpoints from -8 to 24 degrees C. The performance and accuracy of the calorimeter were tested using 20 per cent CO2 in N2 infusion and butane burning. Agreement between the theoretical and the measured values was found to be 99 per cent for VO2 and 100 per cent for VCO2 with a precision for both gases of +/- 10 ml/min over a 1-h period. PMID- 2269252 TI - Natural killer cell activity in alcoholic cirrhosis: influence of nutrition. AB - Forty-five patients with alcoholic cirrhosis, 20 chronic alcoholics with normal liver function tests and 36 healthy subjects were investigated. A combined index of nine anthropometric and biochemical parameters (triceps skinfold, arm muscle circumference, mid-arm muscle area, body fat percentage, creatinine-height index, serum albumin, plasma transferrin, prealbumin and retinol-binding protein levels) was used to evaluate nutritional status, allowing a distinction to be made between those patients with adequate nutrition (group I: 40 per cent of cirrhotics and 55 per cent of alcoholics), those with slight malnutrition (group II: 37.7 per cent of cirrhotics and 45 per cent of alcoholics) and those with severe malnutrition (group III: 22.2 per cent of cirrhotics and none alcoholic). Natural Killer (NK) cell activity of peripheral blood lymphocytes was determined using a 51Cr releasing cytotoxicity assay against K562 target cells. This was significantly lower in the cirrhotics than in the controls and chronic alcoholics (P less than 0.001 and P less than 0.01 respectively), but there was no difference between the latter two groups. Natural Killer activity was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with adequate nutrition, suggesting that malnutrition may play a role in the onset of the immunological disorder. No relationship could be established between nutritional status, NK activity and the clinical activity of the disease using Orrego's index on the liver function tests. PMID- 2269253 TI - Resting and sleeping energy expenditure in the elderly. AB - An estimate of a patient's energy needs is usually derived from equations, which predict energy expenditure (EE) by considering sex, age and body weight. Due to the increasing number of elderly people in a hospital population, more data on energy requirements in this age-group are needed. In this study resting energy expenditure (REE) of 40 healthy men and women, aged 51-82 years, was measured using a ventilated hood system. The results showed that some commonly used prediction equations underestimated REE by approximately 6 per cent. REE was highly correlated with fat free mass (FFM) (r = 0.88; P less than 0.001) and body weight (r = 0.85; P less than 0.001). A stepwise multiple regression analysis showed that the combination of body weight, sex and age resulted in the best prediction for REE; REE (kcal) = 1641 + 10.7 weight (kg)--9.0 age (years)--203 sex (1 = male, 2 = female) (r = 0.92). However, REE of an individual may be over- or underestimated by +/- 225 kcal (10-20 per cent) due to large between-subject variations. We suggest therefore that the energy requirements of elderly people should be measured rather than predicted. Due to small within-subject variations (including measurement error) a single REE measurement would suffice. Sleeping energy expenditure (SEE) was 7 per cent lower than REE. PMID- 2269254 TI - Bedside and field methods for assessing body composition: comparison with the deuterium dilution technique. AB - Estimates of body composition by the deuterium dilution technique were made in 55 healthy subjects (38 men and 17 women) with a mean age of 28.4 years, weight 65.5 kg and height 173.7 cm (body mass index 16.9-29.4 kg/m2). The results were compared with estimates obtained in the same subjects by 5 bedside techniques (skinfold thickness, impedance, resistance and 2 equations predicting body composition from weight and height). The results of all the bedside predictive methods were found to differ significantly from those of the deuterium dilution method (P less than 0.001). The Holtain impedance method underestimated the fat free mass (FFM) obtained by deuterium dilution (50.8 +/- 7.9 kg) by a mean difference (mean bias) of 4.1 kg while the other methods overestimated FFM (mean bias or mean difference of -1.3 to -2.4 kg). The resistance (Valhalla equations) and skinfold methods showed the narrowest 95 per cent limits of agreement, when compared with the deuterium dilution technique, while the weight and height equations showed the widest limits of agreement. It is concluded that in this population, the resistance (Valhalla equations) and the skinfold thickness methods were the best predictors of body composition as measured by deuterium dilution. Discrepancies between the bedside methods and deuterium dilution method may be due to (a) methodological or biological differences between the test population used in this study and the original population used to validate the method, (b) differences in the structure of the equations used to interpret the measured biological variables, such as impedance and resistance, and (c) the use of predictive equations that are based on different 'reference' methods, such as deuterium dilution or densitometry, and on different assumptions. Predictive equations based on a combination of these reference methods are preferable to those based on single methods. PMID- 2269255 TI - Bioelectrical impedance, anthropometry and body composition in stunted and non stunted children. AB - Bioelectrical impedance (BIA) and anthropometric measurements were taken of 129 stunted and 32 non-stunted children aged 9-24 months in Kingston, Jamaica. The reliability of BIA in such young children was examined and the relationships between impedance and anthropometry were determined. The stunted children had significantly lower body mass index (BMI) and smaller triceps skinfolds than the non-stunted children, suggesting differences in body composition between the groups. Resistance was significantly higher in the stunted children than the non stunted children and nutritional group (stunted or non-stunted) contributed significantly to the variance in resistance after controlling for length, weight, mid-upper arm circumference, triceps and subscapular skinfolds, age and sex. This suggests that there were differences in body composition and/or body shape between the groups beyond that measured by the anthropometric indices used. Total body water (TBW) was estimated using an equation for Jamaican children of comparable age. As a percentage of body weight the TBW estimates were the same for the two groups, a finding which is inconsistent with the anthropometric data. PMID- 2269256 TI - Gamete lifespans in the mare's genital tract. PMID- 2269257 TI - Echocardiography and left ventricular function. PMID- 2269258 TI - Digital blood flow, arteriovenous anastomoses and laminitis. PMID- 2269259 TI - Cardiopulmonary effects of xylazine sedation in the foal. AB - Six healthy foals underwent instrumentation for measurement of the cardiopulmonary effects of sedation with 1.1 mg/kg bodyweight xylazine hydrochloride given intravenously. Responses to xylazine in foals at 10 and 28 days of age were not significantly different. Foals became sedate and markedly ataxic, and four of the six foals became recumbent. Heart rate decreased significantly but no arrhythmias were detected. Arterial blood pressure increased initially and then fell significantly below pre-injection values. Changes in respiratory airflow, upper airway obstruction and respiratory noise were noted in the initial 20 mins of sedation, after which respiratory rate fell, tidal volume increased, and minute volume decreased gradually. Arterial blood gas tensions and pH did not change significantly during the 120 mins following xylazine administration. Control studies showed no significant changes. All foals recovered uneventfully. PMID- 2269260 TI - Anatomical validation of two-dimensional echocardiography in the horse. AB - This study was performed on 15 horses to validate the cardiac anatomy as imaged with two dimensional echocardiography (2DE) and to determine the accuracy of intracardiac measurements. 2DE images were recorded in five horses in life with a Diasonics DRF100 ultrasound system and a 3.5 MHz transducer in different tomographic planes. After slaughter, the hearts were fixed in 10 per cent formalin. To compare in vivo and in vitro results, the specimens were suspended in a water-filled tank and 2DE images were made using the same transducer positions as in life. In vitro 2DE and autopsy measurements of the same planes and parameters were also taken on a further 10 hearts, and the results were statistically compared. The in vivo 2DE images corresponded well with both in vitro 2DE recordings and anatomical sections. Repeatable imaging of each tomographic plane was possible on the post mortem hearts using intracardiac reference points. Comparison of parameters measured during in vitro 2DE and autopsy demonstrated a significant correlation between all 2DE and autopsy data (r: 0.879 to 0.926; P less than 0.001). Repeated 2DE measurements of each parameter showed a good reproducibility with coefficients of variation (CV%) varying between 4.6 to 10.6 per cent. The results suggest that 2DE is a reliable method for accurate anatomical evaluation of the equine heart and show the potential application of quantitative two dimensional echocardiography in the living horse. PMID- 2269261 TI - Left ventricular volume determination in the horse by two-dimensional echocardiography: an in vitro study. AB - This study was designed to evaluate the accuracy of two-dimensional echocardiography (2DE) in determining the left ventricular volume (LVV) of the horse in vitro. After examining the shape of the left ventricular silicon rubber casts of four equine hearts, two modified Simpson's rule methods (Model A and Model B) as combinations of conical shapes and one biplane area-length method as a single cone (Model C) were chosen for volume calculations. One long axis and three short axis planes were used for linear and area 2DE measurements, respectively. The ventricular length (L) was calculated from the chordal length (CL) by using a linear regression equation (L = 5.54 + 1.83 CL) obtained by anatomical measurement of these two parameters on 40 normal hearts. The LVV was calculated in 15 formalin-fixed hearts from 2DE measurements with the three geometric models. Left ventricular casts were then made using silicon rubber, and their volumes were determined by water displacement. The calculated volumes were plotted against cast volumes with linear regression analysis. All calculated LVVs correlated well with the cast LVVs (R = 0.921 to 0.957; P less than 0.001). The highest correlation was provided by Model A which best represented the shape of the left ventricle. This model consisted of a truncated cone bordered by the area at the level of the mitral valve and by the area at the level of the chordae tendineae, plus a cone the base of which was the area at the level of the papillary muscles. The results demonstrate the applicability of 2DE for equine LVV determinations in vitro, similar to other species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269262 TI - An investigation of the second heart sound in the normal horse. AB - The second heart sound was evaluated in conscious, normal horses using intracardiac and external sound detection devices and echocardiography. The second heart sound (S2) in the normal horse is single or split by a narrow interval, not usually detected by external phonocardiographic evaluation. Splitting of S2 was classified as normal (aortic [A2] preceding pulmonic [P2] components) in 66.7 per cent and reversed (P2 preceding A2) in 33.3 per cent of the horses studied. Normal splitting appears to result from lower impedance of the pulmonary vasculature delaying the onset of P2. Reverse splitting appears to result from a delay in A2 resulting from prolongation of PEP and LVET. There does not appear to be variation in splitting of S2 due to respiration based on the cases in which this was measured. PMID- 2269263 TI - A tracheoscopic technique for obtaining uncontaminated lower airway secretions for bacterial culture in the horse. PMID- 2269264 TI - Effects of time of insemination relative to ovulation on pregnancy rate and embryonic-loss rate in mares. AB - The effects of pre-ovulatory and post ovulatory insemination on pregnancy rate and embryonic-loss rate were studied in 268 mares in two experiments. Within each experiment mares were randomised within replicates as follows: to be inseminated on the day the pre-ovulatory follicle reached 35 mm (pre-ovulatory group), to be inseminated on the day of ovulation (Day 0 group), and to be inseminated on the day after ovulation (Day 1 group). Ultrasonic pregnancy diagnoses were performed on Days 11, 12, 13 and 14 (Experiment 1) and Days 11, 12, 13, 14, 15, 20 and 40 (Experiment 2). Combined for the two experiments, pregnancy rates were different (P less than 0.01) among the three groups. For Experiment 2, pregnancy rate within the pre-ovulatory group was lower (P less than 0.05) for insemination 4 days or more before ovulation than for up to 3 days before ovulation. Pregnancy rate was lower (P less than 0.05) for the Day 0 group than for the pre-ovulatory group inseminated up to 3 days before ovulation. In Experiment 2, ovulation was detected by examinations every 6 h; pregnancy rate was greater (P less than 0.05) for mares inseminated 0 to 6 h after ovulation than for mares inseminated at 18 to 24 h. No pregnancies occurred when mares were inseminated 30 h or more after ovulation. The mean day of first detection of the embryonic vesicle was different (P less than 0.0001) among the three groups. Diameter of embryonic vesicle averaged over Days 11 to 15 also differed (P less than 0.0001) among groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269265 TI - Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis. AB - Scintigraphy was used to evaluate digital circulation at 24 h intervals in 11 control horses and in nine horses affected with acute laminitis created by administration of a high-starch ration. Following intra-arterial injection of technetium-99m macroaggregated albumin into the brachiocephalic trunk, static images were acquired of the right front foot. Dynamic radionuclide angiograms and static blood pool images were also obtained after jugular vein injection of technetium-99m diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquillisation. Images were analysed quantitatively for parameters indicative of circulation to the whole foot and to specific regions within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Total flow tended to increase throughout the peripheral/external regions of the foot, but statistically significant elevations were consistently present only within the lamellae. The increased total blood flow to the lamellae may have been due to elevated capillary flow and/or elevated arteriovenous shunt flow. This study did not support lamellar ischaemia as the primary cause of acute equine laminitis. PMID- 2269266 TI - Inflammatory components in uterine fluid from mares with experimentally induced bacterial endometritis. AB - Exudate and uterine flushings were collected at either 30, 60, 120 or 240 mins after intrauterine infusions of Streptococcus zooepidemicus in genitally normal mares during oestrus. Uteri were also flushed without prior induction of endometritis. Protein concentrations in exudate and flushings increased with time and exudate pH decreased with time; the pH of flushings did not alter. Lysozyme and lactate dehydrogenase were present in flushings from non-infected uteri, but concentrations increased with time after infection. Immunoreactive prostaglandin E2 was undetectable before infection, but concentrations rose after infection. No neutrophils were present in non-infected flushings but, by 30 mins, there were significant (P less than 0.01) neutrophil numbers in exudate and flushings; thereafter numbers increased, particularly in exudate. Acute endometritis resembled acute inflammation at other sites in the horse and a significant response had occurred by 30 mins after experimental infection. PMID- 2269267 TI - The effects of copper supplementation on the prevalence of cartilage lesions in foals. AB - The potential role of dietary copper in the development of cartilage defects in foals was investigated. Twenty-one mares were fed rations containing 13 ppm copper (CuC, control) or 32 ppm copper (CuS, supplemented) during the last three to six months of gestation and first three months of lactation. Their foals were fed pelleted concentrate containing 15 or 55 ppm Cu and were destroyed at 90 (5 CuC and 5 CuS foals) or 180 (6 CuC and 5 CuS foals) days. Focal cartilage lesions were found at multiple sites on necropsy. In foals killed at 90 days, there were over twice (9 versus 4) as many lesions of osteochondrosis and more than four times (9 versus 2) as many articular lesions of osteophyte formation or thinning in CuC foals compared with CuS foals. These differences were due predominantly to a higher number of lesions in one CuC foal. Two 90-day CuC foals had osteochondrosis of articular-epiphyseal (A-E) complex, one with thickenings and separation from subchondral bone and one with subchondral fibrosis. One 90-day CuS foal had a cartilage thickening of the A-E complex in the tibiotarsal joint with separation from subchondral bone. In foals killed at 180 days, there were seven times more articular lesions (21 versus 3) of osteophyte formation or thinning, nearly twice as many lesions of osteochondrosis (13 versus 8) [corrected] in the physis and over five times as many involving the A-E complex (11 versus 2) in six CuC foals compared with five CuS foals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269268 TI - Effects of five hours of constant 1.2 MAC halothane in sternally recumbent, spontaneously breathing horses. AB - Circulatory and respiratory effects of five h of constant 1.06 per cent alveolar halothane in oxygen were identified in eight healthy horses, which breathed spontaneously, were otherwise unmedicated and positioned in sternal recumbency. Only a few important significant (P less than 0.05) changes occurred with time. Total peripheral resistance was about 15 per cent lower after two hours of constant dose halothane than after 30 mins of constant dose (P less than 0.05) and accounted for the significant 10 per cent reduction in mean carotid arterial blood pressure. By 5 h, the reduction in resistance and arterial blood pressure was 20 and 25 per cent respectively. Heart rate increased progressively with time and the increase became significant at 5 h (15 per cent increase). However, the heart rate change was not large enough to alter cardiac output. There were no major time-related changes in PaO2 or PaCO2. Three of four horses recovered from anaesthesia had markedly elevated serum creatine kinase levels and clinical signs of severe post anaesthetic myopathy. PMID- 2269270 TI - Suspected congenital origin of bilateral hydrosalpinx in a jenny donkey. PMID- 2269269 TI - Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse. AB - Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. These effects were transient, and the animals appeared normal within 30 mins of dosing. Treated horses were tested in a variable interval responding apparatus 30 mins after dosing and no residual stimulation or depressant effects of hordenine were apparent. Animals dosed orally with 2.0 mg/kg bwt of hordenine showed no changes in heart rate, respiratory rate, basal body temperature or behaviour. After iv injection of hordenine, (2.0 mg/kg bwt) plasma reached a maximum value of about 1.0 micrograms/ml, and declined thereafter in a biexponential fashion. Kinetics of plasma concentration satisfied the concept of a two compartment open system, with an alpha-phase half-life of about 3 mins, and a beta-phase half-life of about 35 mins. Total urinary concentrations of hordenine (free and conjugated) peaked at about 400 micrograms/ml, and then declined exponentially to background levels by 24 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269271 TI - Recent advances in the molecular analysis of inherited disease. AB - Many important human genes have been cloned during the last ten years. In some cases, using reverse genetic techniques [Orkin, S. H. (1986) Cell 47, 845-850], disease-causing genes have been isolated whose product was previously unknown. Important examples include the dystrophin protein which, when mutated, gives rise to either Duchenne or Becker muscular dystrophy [Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C. and Kunkel, L. M. (1987) Cell 50, 509 517; Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S. & Kunkel, L. M. (1988) Genomics 2, 90-95; Koenig, M., Monaco, A. P. & Kunkel, L. M. (1988) Cell 53, 219 228] and the cystic fibrosis transmembrane conductance regulator (CFTR) [Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., Drumm, M. L., Ianuzzi, M. C., Collins, F. S. & Tsui, L.-C. (1989) Science 245, 1066-1073]. Recently the technology for systematically detecting single base-pair changes by chemical methods, enzymatic methods or direct DNA sequencing has greatly expanded and simplified. In addition to providing structural information about these clinically important genes and information on disease-causing mutations, these studies have led to an increased understanding of mechanisms of mutation, to the discovery of novel genetic mechanisms and to important clinical applications of carrier detection and pre-natal diagnosis. The recent rapid progress has been made possible by the development of DNA amplification using the polymerase chain reaction (pcr) invented by Saiki and colleagues [Saiki, R. K., Chang, C-A., Levenson, C. H., Warren, T. C., Boehm, C. D., Kazazian, H. H. & Ehrlich, H. A. (1988) N. Engl. J. Med. 319, 537-541]. PMID- 2269272 TI - Hemoglobin Saint Mande [beta 102 (G4) Asn----Tyr]. Functional studies and structural modeling reveal an altered T state. AB - Oxygen equilibrium studies of purified hemoglobin Saint Mande (Hb SM) [beta 102 (G4) Asn----Tyr] reveal a decreased oxygen affinity and cooperativity but to a lesser extent than found for Hb Kansas (beta 102 Thr). The low affinity of Hb SM depends on environmental conditions: eliminating chloride or raising the pH greatly elevated the ratio of p50 of Hb SM to that of Hb A. The alkaline Bohr effect is reduced by about 40%. The effects of anions (chloride, organophosphates) binding to deoxy Hb SM are also reduced. These data indicate that the functional properties of Hb SM are intermediary between Hb A and Hb Kansas. In addition, molecular graphics modeling of Hb SM in the oxy and deoxy structures indicate the possibility of a new hydrogen bond in the T state between beta(1)102 Tyr and alpha(2)42 Tyr. Stabilisation of the T state in this manner is a plausible explanation for several of the effects observed. PMID- 2269273 TI - The synthesis of 3-phosphonoalanine, phosphonopyruvic acid and phosphonolactic acid. Scission of the C-P bond during diazotization of phosphonoalanine. AB - 3-Phosphonoalanine has been made by the Strecker synthesis from phosphonoacetaldehyde, which is easily prepared from vinyl acetate. It gives phosphonopyruvate by transamination when treated with glyoxylate. Phosphonolactate, an analogue of phosphoglycerate, is prepared by reducing phosphonopyruvate. Diazotization of phosphonoalanine was investigated as a route for making phosphonolactate: addition of NaNO2 to the isoelectric form of phosphonoalanine gave much scission of the C-P bond with release of phosphate; addition of HBr prevented this release and gave largely the bromo acid. The supplement reports the synthesis of arsonolactate, a similar analogue, by treating chlorolactate with alkaline arsenite. PMID- 2269274 TI - Content, pattern and metabolic processing of rat-liver gangliosides during liver regeneration. AB - During rat liver regeneration, the ganglioside content and distribution undergo significant changes after partial hepatectomy; total liver gangliosides increase remarkably till the 4th day after surgery, thereafter progressively decreasing to reach the values of sham-operated controls at the 12th day. The qualitative pattern is characterized by the 95% relative increase of GD1a at the 4th day and the 40% relative decrease of GD1b. In order to investigate the processes of ganglioside penetration into cells, degradation and biosynthesis, radiolabelled GM1 ([Sph-3H] GM1) was administered. One day after hepatectomy the liver uptake and metabolism of exogenous ganglioside were significantly reduced. Three days post-surgery these parameters were restored to control values; however an increased radioactivity incorporation was found in GD1a, thus suggesting an enhancement of its biosynthesis around the 4th day. The data reported here suggest that in the first two days after partial hepatectomy, the ganglioside degradation is reduced with a consequent increase of ganglioside content; later on the catabolic routes normalize and some biosynthetic processes leading to GD1a are enhanced. GD1a seems to be a marker of a peculiar transition phase of liver regeneration. PMID- 2269275 TI - Analysis of the membrane potential of rat- and mouse-liver mitochondria by flow cytometry and possible applications. AB - Washed and purified rat- or mouse-liver mitochondria exhibiting high membrane integrity and metabolic activity were studied by flow cytometry. The electrophoretic accumulation/redistribution of cationic lipophilic probes, rhodamine 123, safranine O and a cyanine derivative, 3,3' dihexyloxadicarbocyanine iodide, during the energization process was studied and was consistent with the generation of a negative internal membrane potential. An exception to this was nonylacridine orange which spontaneously bound to the mitochondrial membrane by hydrophobic interactions via its hydrocarbon chain. Energized purified mitochondria stained with potentiometric dyes exhibited both higher fluorescence and population homogeneity than the non-energized or deenergized (nigericin plus valinomycin) mitochondria. By contrast, under non energized or deenergized conditions, the mitochondrial population exhibited fluorescence intensity heterogeneity related to the residual membrane potential; two subpopulations were evident, one of low fluorescence which may be related to the autofluorescence of the mitochondria (plus non-specific dye binding) and a second population which exhibited high fluorescence. Flow cytometry of the unpurified, simply washed, rat-liver mitochondria stained with rhodamine 123, a classically used dye, provided evidence of their heterogeneity in terms of light scattering properties and membrane-potential-related fluorescence. One third of the washed mitochondria were found to be non-functional by such assays. The fluorescence of purified rat-liver mitochondria due to the membrane potential built up by endogenous substrates indicates heterogeneity of the mitochondrial population with respect to levels of endogenous substrates. The low-angle light scattering increases upon energization and provides some original information about the shape and modification of the inner mitochondrial conformation accompanying the energization. The heterogeneity of the rat liver mitochondrial population, from a structural, metabolic (existence of endogenous substrates) and functional (active and non-active mitochondrial population dispersion) point of view could thus be demonstrated by flow-cytometry analysis. Two animal models were examined with regard to the alteration of the mitochondrial membrane potential under the effects of drugs (rat-liver mitochondria), and the effects of ammonium toxicity (mouse-liver mitochondria). These results are promising and open new perspectives in the study of mitochondriopathies. PMID- 2269276 TI - On the mechanistic origin of damped oscillations in biochemical reaction systems. AB - A generalized reaction scheme for the kinetic interaction of two reactants in a metabolic pathway has been examined in order to establish what minimal mechanistic patterns are required to support a damped oscillatory transient-state kinetic behaviour of such a two-component system when operating near a steady state. All potentially oscillating sub-systems inherent in this scheme are listed and briefly characterized. The list includes several mechanistic patterns that may be frequently encountered in biological system (e.g. involving feedback inhibition, feed-forward activation, substrate inhibition or product activation), but also draw attention to some hitherto unforeseen mechanisms by which the kinetic interaction of two metabolites may trigger damped oscillations. The results can be used to identify possible sources of oscillations in metabolic pathways without detailed knowledge about the explicit rate equations that apply. PMID- 2269277 TI - Physicochemical and biological characterization of asialoerythropoietin. Suppressive effects of sialic acid in the expression of biological activity of human erythropoietin in vitro. AB - Various partially or fully desialylated human erythropoietins were obtained by neuraminidase digestion of the hormone, without non-specific proteolysis and degradation of carbohydrates. Asialoerythropoietin showed a specific activity of 220-IU/mg protein in vivo, although that of the intact erythropoietin was 2.2 x 10(5) IU/mg. A linear relationship was found between the logarithm of the specific activity in vivo and the number of sialic acids. The asialoerythropoietin showed a four-times-higher specific activity in vitro compared with intact erythropoietin using mouse bone marrow cells. It also showed an approximately six-times-higher specific activity in a colony-forming assay for the erythroid colony-forming unit and the erythroid burst-forming unit. Partially or fully de-N-glycosylated erythropoietin derivatives also showed lower in vivo activity but higher in vitro activity than the intact erythropoietin, dependent on the number of sialic acids. To clarify the reason for the enhanced biological activity of asialoerythropoietin in vitro, the binding of intact 125I erythropoietin or 125I-asialoerythropoietin to cells containing specific receptors for the hormone was analyzed. 125I-asialoerythropoietin bound to spleen cells from anemic mice approximately five times faster than did intact 125I erythropoietin. The amount of 125I-asialoerythropoietin internalized by target cells, measured in the absence of NaN3, was four times higher than that of intact erythropoietin. These results demonstrate that asialoerythropoietin binds to its receptor faster than the intact form. This may be the main reason for the increased activity of asialoerythropoietin in vitro. PMID- 2269278 TI - Thermodynamics of information transfer between subunits in oligomeric enzymes and kinetic cooperativity. 1. Thermodynamics of subunit interactions, partition functions and enzyme reaction rate. AB - The strength of quaternary constraints between two subunits of a polymeric enzyme depends upon the number of neighboring subunits and upon whether these subunits are liganded or not. These quaternary constraints between two subunits of a complex polymeric enzyme may be expressed, however, in terms of quaternary constraints that exist within ideal dimers. The influence of quaternary constraints on the reaction rate of a complex polymeric enzyme may thus be expressed in terms of the intersubunit strain that exists within dimers. This conclusion, that was far from evident, appears to be the consequence of the postulates of structural kinetics, and derive as well from usual thermodynamic principles. The structural steady-state equations may be expressed in terms of partition and sub-partition functions. As applied to structural kinetic models, a partition function expresses how, during the steady state, the energy of a population of enzyme molecules is distributed over n states. Similarly a sub partition function describes how, during the steady state, the energy of these enzyme molecules is partitioned among only n-k of these states. Although the concept of partition function was initially formulated for equilibrium processes, it may be extended without any loss of generality to non-equilibrium processes. Moreover it is reminiscent of the concept of binding polynomial presented some years ago by Wyman for the equilibrium binding of a ligand to a protein. With this formalism derived from statistical mechanics, a structural rate equation may be derived from the ratio of a sub-partition function of degree n-1 and of a partition function of degree n. Again these properties are the consequence of the postulates of structural kinetics associated with simple ideas derived from statistical thermodynamics. PMID- 2269279 TI - Thermodynamics of information transfer between subunits in oligomeric enzymes and kinetic cooperativity. 2. Thermodynamics of kinetic cooperativity. AB - The principles of structural kinetics allow one to define the thermodynamic conditions that are sufficient to generate a certain type of kinetic behavior. If subunits are loosely coupled, that is if no quaternary constraint exists between them, the kinetic behavior of the polymeric enzyme is qualitatively defined by the behavior of an ideal dimer. The nature and the extent of the kinetic cooperativity are defined by the energy of interaction, delta G rho, between two subunits. This energy of interaction is that of an ideal dimer relative to that of the A2 and B2 states. This thermodynamic formulation of a given type of cooperativity holds whatever the degree of polymerization of the enzyme. Under these conditions of loose coupling between subunits, positive kinetic cooperativity cannot be associated with any sigmoidicity of the rate curve. The range of energy coupling where positive kinetic cooperativity must, of necessity, be observed becomes more and more narrow as the number of subunit interactions is increased. This range, however, is independent of the number of subunits. The same situation is not observed for negative cooperativity which appears to be independent of both the number of subunits and the number of subunit interactions. If the subunits are tightly coupled, that is if quaternary constraints exist between them, three thermodynamic parameters, delta G' rho, delta G lambda, delta G mu, are required to define the nature of kinetic cooperativity. delta G' rho is the free energy of an ideal strained dimer relative to that of strained A2 and B2 states. delta G lambda and delta G mu represent the difference of strain energies between conformations A and B and B and B relative to that existing between conformations A and A. One may determine in the parametric space (delta G' rho, delta G lambda, delta G mu) the boundaries between the sufficient conditions that generate a certain type of cooperativity and the lack of these conditions. The kinetic parameters of the rate equation are not all independent. A number of constraint conditions exist between them which depend upon the subunit design of the polymeric enzyme. The existence of these constraint conditions may be diagnostic of a certain type of subunit interactions. PMID- 2269280 TI - A plant serpin gene. Structure, organization and expression of the gene encoding barley protein Z4. AB - A 3133-bp nucleotide sequence of the gene Paz1 on chromosome 4 of barley, encoding endosperm protein Z4, has been determined. The sequence includes 1079 bp 5' upstream and 523 bp 3' downstream of the coding region. The 1079-bp 5' upstream region of the gene shows little similarity to 5' regions of other sequences genes expressed in the developing cereal endosperm. The coding sequence is interrupted by one 334-bp-long intron (bases 1497-1830). The deduced amino acid sequence, which was corroborated by peptide sequences, consists of 399 amino acids and has a molecular mass of 43,128 Da. This sequence confirms protein Z4 to be a member of the serpin superfamily of proteins. The similarity with other members of the family expressed as amino acids in identical positions is in the order of 25-30% and pronounced in the carboxy-terminal half of the molecule. Sequence residues assumed to form clusters stabilizing the tertiary structure are highly conserved. Protein Z4 is synthesized in the developing endosperm without a signal peptide and protein Z4 mRNA was evenly distributed among the free and membrane-bound polyribosomes of the endosperm cell. An internal hydrophobic region of 21 amino acids (residues 36-56) may serve as a signal for targeting the polypeptide into the lumen of the endoplasmic reticulum. The gene for protein Z4 could not be detected in the barley variety Maskin and some of its descendants. The 'high-lysine' allees, lys1 (Hiproly barley) and lys3a (Bomi mutant 1508) on chromosome 7, enhance and repress, respectively, the expression of the protein Z4 gene. Also, 1554 bp of another 8-kbp fragment of the barley genome Paz psi, similar to the protein-Z4-coding region, have been determined. Small insertions and deletions and the presence of an internal stop codon identify this fragment as part of a pseudogene related to the protein Z4 gene. PMID- 2269281 TI - Direct repeats in the non-coding region of rabbit mitochondrial DNA. Involvement in the generation of intra- and inter-individual heterogeneity. AB - In rabbit we observed heteroplasmy at an exceptionally high level, the heterogeneity occurring within the non-coding region of the DNA. Mitochondrial DNA (mt DNA) was cloned in pBR322 and the nucleotide sequence analysis of an EcoRI-Hind III fragment encompassing the non-coding region revealed that although there are common features with other mammalian mtDNAs (termed large central conserved-sequence block, conserved-sequence blocks 1, 2 and 3 and termination associated elements) the non-coding region shows an unusual organization; two stretches of tandem repeats of 20 bp and 153 bp are present in a part containing the origin of H-strand replication (OH) and probably the promoters for transcription as judged from other vertebrates. The long repeats are located between tRNA(Phe) and conserved sequence block 3 and the short repeats are located between conserved sequence blocks 1 and 2. When cloned in Escherichia coli (recA or recBC sbcb) DNA fragments containing the short repeats show length differences corresponding to various copy numbers of repeats. Electrophoretic analysis of the appropriate restriction fragments of rabbit mtDNA reveals extended intra- and inter-individual length heterogeneity. Both sets of repeats are involved in the generation of heterogeneity and are present in variable copy numbers from one mtDNA molecule to another. Moreover, rearrangement of the motives of the short repeat are observed to different extents in the mtDNA from one animal to another. The occurrence, maintenance and possible involvement of these repeated sequences, capable of forming stable secondary structures, are discussed in relation to their location in the region of control signals. PMID- 2269282 TI - Cloning, nucleotide sequence and regulation of the Salmonella typhimurium pyrD gene encoding dihydroorotate dehydrogenase. AB - The Salmonella typhimurium pyrD gene encoding dihydroorotate dehydrogenase was cloned and sequenced. In total, a sequence of 1286 nucleotide pairs was determined wherein a single open-reading-frame of 1011 bp, encoding a polypeptide of 336 amino acids having 95% similarity with the Escherichia coli pyrD gene product, was identified. A region of hyphenated-dyad symmetry exists within the leader region affording the potential for the formation of a stable secondary structure in the 5' end of the transcript. Mutations from several regulatory mutants were located within the region of dyad symmetry which would impart changes in the transcript within the putative secondary structure, implicating the secondary structure in regulation. Primer extension analysis revealed multiple transcriptional start sites located six to nine nucleotides downstream from the Pribnow box, with the primary initiation site differing in repressing and derepressing growth conditions. The results are discussed in terms of a translational attenuation model for regulation of pyrD expression. PMID- 2269283 TI - Isolation and characterization of an inhibitor of ribosome-dependent GTP hydrolysis by elongation factor G. AB - Two inhibitors of ribosome-dependent GTP hydrolysis by elongation factor (EF)G were found in the ribosome wash of Escherichia coli strain B. One of these inhibitors was purified to homogeneity and characterized. The isolated inhibitor was found to consist of two polypeptide subunits with apparent molecular masses of 23 kDa and 10 kDa. Inhibition of EF-G GTPase could not be overcome by increasing amounts of the elongation factor or high concentrations of GTP, but was reversed by large amounts of ribosomes. The effect of the inhibitor was reduced by increasing concentrations of either 30S or 50S ribosomal subunits. EF G-dependent GTPase of 50S ribosomal subunits was not affected by the inhibitor. These findings clearly show that the inhibitor interferes with the modulation of EF-G GTPase activity by the interactions between 30S and 50S ribosomal subunits. Under conditions, where 30S CsCl core particles are able to associate with 50S subunits and to stimulate EF-G GTPase, the effect of the inhibitor was considerably reduced when intact 30S ribosomal subunits were substituted by 30S CsCl core particles. This finding indicates that 30S CsCl split proteins are important for the action of the inhibitor and that the inhibitor does not affect the EF-G GTPase merely by interfering with the association of ribosomal subunits. Furthermore, poly(U)-dependent poly(phenylalanine) synthesis was considerably less sensitive to the inhibitor than EF-G GTPase. When ribosomes were preincubated with poly(U) and Phe-tRNA(Phe), poly(phenylalanine) synthesis was considerably less affected by the inhibitor, whereas EF-G GTPase was still sensitive. PMID- 2269285 TI - Limited proteolysis of gamma II-crystallin from calf eye lens. Physicochemical studies on the N-terminal domain and the intact two-domain protein. AB - Gamma II-crystallin from calf eye lens consists of two homologous domains, connected by a six-residue linker peptide. In order to study the intrinsic properties of the domains and their mutual stabilization, limited proteolysis was applied. Optimum conditions providing a homogeneous 10-kDa fragment at high yield were pepsin cleavage in 0.1 M NaCl/HCl pH 2.0, in the presence of 3.0 M urea. Determination of the N-terminus and the C-terminal sequence showed that cleavage occurred at the Phe88-Arg89 peptide bond, giving rise to the complete N-terminal domain including the connecting hexapeptide. The C-terminal part of the polypeptide chain is cleaved to small fragments. Comparing the spectral properties of the isolated N-terminal domain and intact gamma II-crystallin proved the structure of the fragment to be closely similar to that of the native domain. Small differences in absorbance, fluorescence emission and circular dichroism point to alterations caused by the increase in surface area as a consequence of domain separation. The resistance of the 10-kDa fragment toward thermal and alkaline denaturation, as well as unfolding in the presence of urea or guanidine . HCl is decreased, due to the lack of domain interactions stabilizing the intact protein. Unfolding/folding kinetics of the 10-kDa fragment coincide with the second phase of the bimodal transition of intact gamma II crystallin, in agreement with independent sequential folding and modular assembly of the domains within the native molecule. PMID- 2269284 TI - Avian alcohol dehydrogenase: the chicken liver enzyme. Primary structure, cDNA cloning, and relationships to other alcohol dehydrogenases. AB - The major ethanol-active form of chicken liver alcohol dehydrogenase was characterized. The primary structure was determined by peptide analysis and, to a large part, was also deduced by cDNA analysis of a near full-length cDNA clone. The latter was detected by screening of a chicken liver cDNA library with antibodies raised against the purified dehydrogenase. The structure shows that the avian enzyme exhibits characteristics of the complex mammalian alcohol dehydrogenase system, tracing its origin and divergence, and allowing functional correlations. The chicken protein analyzed proves to be a class I alcohol dehydrogenase, with 74% residue identity to gamma chains of the human enzyme, a Km for ethanol of 0.5 mM and a Ki for 4-methyl pyrazole of 2.5 microM. Relationships to the other two classes are non-identical; residue exchanges towards the human classes increase in the order I less than III less than II, and human/chicken differences are less than inter-class differences. Consequently, the origins of the classes are more distant than the avian/mammalian separation. They reflect duplicatory events separated in time, and the lines that lead to present-day classes I and II deviate early. Integrated with the data for the quail enzyme, the structure of the chicken protein shows that within the avian enzymes the degree of variation is comparable to that within the mammalian class I enzymes, which are more variable than the class III forms. The coenzyme-binding and substrate-binding residues of this chicken alcohol dehydrogenase are largely identical to those in the mammalian class I counterparts. However, the subunit interacting areas are more variable and suggest some relationships of the avian enzyme with both class I and III mammalian forms. One of the residues, Gly260 (mammalian class I numbering system), previously considered characteristic of all alcohol dehydrogenases, is replaced by Gln. PMID- 2269286 TI - Structural characterization of a recombinant CD4-IgG hybrid molecule. AB - CD4-IgG is a homodimer of a hybrid polypeptide consisting of the two amino terminal domains (residues 1-180) of human CD4 fused to the hinge region and the second and third constant-sequence (CH2 and CH3) Fc domains (residues 216-441) of human immunoglobulin G (IgG-1). This antibody-like molecule, termed an immunoadhesin, was produced in an effort to combine the binding specificity of CD4 with several potentially desirable properties of IgG molecules [Capon et al. (1989) Nature 337, 525-531]. The structural characteristics of the molecule have been evaluated to demonstrate that CD4-IgG has the same features as the N terminal region of soluble CD4, while retaining those expected for the Fc portion of human IgG. Identification of peptides recovered from the tryptic map confirmed 98.8% of the expected structure of CD4-IgG. The detection of glucosamine in peptides containing Asn257 and the retention time shift of this tryptic peptide after deglycosylation confirmed the presence of Asn-linked oligosaccharides at this position. Four pairs of intrachain and two interchain disulfide bonds were also established. PMID- 2269287 TI - Changes of the oligomeric structure of legumin from pea (Pisum sativum L.) after succinylation. AB - The influence of various levels of succinylation on the structure of the legumin from pea seed has been studied by the techniques of sedimentation velocity, viscometry, fluorescence and circular dichroism spectroscopy, as well as dynamic light scattering. The protein dissociates gradually into the 3S subunit forming a 7S intermediate. At a level of 75-80% succinylation, sudden unfolding of the protein occurs characterized by drastic changes in viscometric and spectroscopic properties. The fluorescence spectra point to the formation of a novel organized structure at a moderate degree of modification before the molecular unfolding takes place. The succinylated subunit was shown to have a sedimentation coefficient of 3.2S, a diffusion coefficient of 5.03 x 10(-7) cm2 . s-1 a Stokes' radius of 4.24 nm, a partial specific volume of 0.703 ml/g, an intrinsic viscosity of 0.13 dl/g, a molar mass of 52.2 kDa and a frictional ratio of 1.74. PMID- 2269288 TI - Assignment of the 1H-NMR spectrum of a lac repressor headpiece-operator complex in H2O and identification of NOEs. Consequences for protein-DNA interaction. AB - A complex between the headpiece amino-terminal residues 1-56 of lac repressor (HP56) and an 11-bp lac operator fragment was studied by 1H NMR. The sequence specific assignment of the exchangeable and non-exchangeable protons has been accomplished. Several protons have favourable chemical shifts in the complex, therefore new intraprotein NOEs could be found that had not been unambigously identified in the free protein. By comparison, most of these intraprotein NOEs are also present in the spectra of the free headpiece but some are different. Furthermore, several new proteins DNA NOEs could be identified. The NOE between the side-chain amide protons of Gln18 and C5H of C7 confirms the specific contact between these residues which was proposed from genetic experiments [Ebright, R. M. (1985) J. Biomol. Struct. & Dyn. 3, 281-297]. The implications of the new data for the interaction between the lac repressor headpiece and its operator are discussed. PMID- 2269289 TI - Modelling of substrate binding to 3-phosphoglycerate kinase with analogues of 3 phosphoglycerate. AB - Two short analogues of 3-phosphoglycerate, -OOC-CHOH-CH2-O-PO32-, phosphonolactate, (-OOC-CHOH-CH2-PO32-) and arsonolactate (-OOC-CHOH-CH2-AsO32-) have been tested with 3-phosphoglycerate kinase. None of these served as substrate for the kinase reaction, unlike the previously studied [Orr, G. A. & Knowles, J. R. (1974) Biochem. J. 141, 721-723] analogues -OOC-CHOH-CH2-CH2-PO32- and -OOC-CHOH-CH2-CH2-AsO32-, which are isosteric with 3-phosphoglycerate. Thus, a decrease in the substrate size and the accompanying stereochemical changes cannot be tolerated by the catalytic mechanism. Instead, both analogues acted as relatively poor competitive inhibitors with respect to both 3-phosphoglycerate and MgATP. AT pH 8.5 and 20 degrees C, the inhibitory constants (Ki) of phosphonolactate and arsnolactate against both substrates are 17 +/- 5 mM and 30 +/- 7 mM, respectively. Surprisingly, however, both analogues proved to be more effective than either 3-phosphoglycerate or its isosteric analogues in protecting the enzyme against modification of its fast-reacting thiols. This comparison suggests that the shorter analogues bind differently, and that the catalytic mechanism demands a precise fitting of the -CH2-O-PO32- segment of the substrate. PMID- 2269290 TI - Purification and fractionation of lipopolysaccharide from gram-negative bacteria by hydrophobic interaction chromatography. AB - By hydrophobic interaction chromatography on octyl-Sepharose, lipopolysaccharide (LPS) of Escherichia coli Re mutant and of wild-type smooth-form (S-form) Salmonella typhimurium and Salmonella abortus equi is fractionated according to increasing amount of fatty acids. Thereby a fractionation of S-form LPS according to the length of the O-polysaccharide chain also occurs, because with increasing of fatty acids there is a decrease in the mean length of the O-polysaccharide chain from approximately 30 to 4 repeating units. Molecular species of Re-mutant LPS contain four 3-hydroxytetradecanoyl residues in addition to which dodecanoic, tetradecanoic and possibly hexadecanoic acid, appear in this sequence. Among the molecular species of S-form LPS, dodecanoic, tetradecanoic and hexadecanoic acids appear in the same order, but in contrast to Re-mutant LPS a significant fraction of S-form LPS contains less than four 3-hydroxytetradecanoyl residues. Hydrophobic interaction chromatography also proved an effective one-step purification procedure of LPS as was shown with a crude preparation from S-form S. typhimurium. PMID- 2269291 TI - The tricarboxylate carrier from rat liver mitochondria. Purification, reconstitution and kinetic characterization. AB - The tricarboxylate carrier from rat liver mitochondria has been purified and reconstituted into phospholipid vesicles. Its activity has been characterized by both a radioactive citrate uptake assay and a coupled enzymatic assay. A Km of 40 microM and a Vmax of 1.56 mumol x min-1 x mg-1 have been determined for the carrier. Cholesterol levels of between 5-10% of total lipid content are shown to cause a decrease in carrier activity. PMID- 2269292 TI - Temperature-induced expression of proteins in Leishmania mexicana amazonensis. A 22-kDa protein is possibly localized in the mitochondrion. AB - Temperature increase is an integral part of Leishmania life cycle, and plays a major role in stage transformation. Analysis of the temperature-dependent pattern of protein synthesis on two-dimensional gel electrophoresis shows that, in addition to the conserved heat-shock type of response in which expression of the major 70-kDa and 83-kDa heat-shock proteins is observed, a group of low-molecular mass (17-40 kDa) proteins is induced in promastigotes of Leishmania mexicana amazonensis at elevated temperatures. Immuno-gold labelling with antibodies raised against the heat-induced 22-kDa proteins was localized mainly in the mitochondrion of Leishmania parasites, though labelling was observed also in the nucleus. The correlation of this finding with various reports on induction of mitochondrial enzymes in response to temperature stress in other organisms is discussed. PMID- 2269293 TI - Self recognition by the immune system. AB - In each organism, the immune system must acquire the ability to distinguish self from nonself. Experiments in T cell receptor transgenic mice indicate that this process involves the selection of lymphocytes in the thymus. PMID- 2269294 TI - Eukaryotic DNA replication. Enzymes and proteins acting at the fork. AB - A complex network of interacting proteins and enzymes is required for DNA replication. Much of our present understanding is derived from studies of the bacterium Escherichia coli and its bacteriophages T4 and T7. These results served as a guideline for the search and the purification of analogous proteins in eukaryotes. model systems for replication, such as the simian virus 40 DNA, lead the way. Generally, DNA replication follows a multistep enzymatic pathway. Separation of the double-helical DNA is performed by DNA helicases. Synthesis of the two daughter strands is conducted by two different DNA polymerases: the leading strand is replicated continuously by DNA polymerase delta and the lagging strand discontinuously in small pieces by DNA polymerase alpha. The latter is complexed to DNA primase, an enzyme in charge of frequent RNA primer syntheses on the lagging strand. Both DNA polymerases require several auxiliary proteins. They appear to make the DNA polymerases processive and to coordinate their functional tasks at the replication fork. 3'----5'-exonuclease, mostly part of the DNA polymerase delta polypeptide, can perform proof-reading by excising incorrectly base-paired nucleotides. The short DNA pieces of the lagging strand, called Okazaki fragments, are processed to a long DNA chain by the combined action of RNase H and 5'----3'-exonuclease, removing the RNA primers, DNA polymerase alpha or beta, filling the gap, and DNA ligase, sealing DNA pieces by phosphodiester bond formation. Torsional stress during DNA replication is released by DNA topoisomerases. In contrast to prokaryotes, DNA replication in eukaryotes not only has to create two identical daughter strands but also must conserve higher order structures like chromatin. PMID- 2269295 TI - Human liver manganese superoxide dismutase. Purification and crystallization, subunit association and sulfhydryl reactivity. AB - Manganese superoxide dismutase (Mn-SOD) has been purified with a high yield (320 mg) from human liver (2 kg) and crystallized. Low-angle laser light scattering of the enzyme has shown that native enzyme is a tetrametic form. Four of the eight cysteine residues in the tetramer reacted with 5,5'-dithiobis(2-nitrobenzoic acid) or with iodoacetamide. The others were only reactive in protein heated with SDS or urea after reduction with dithiothreitol or 2-mercaptoethanol. The reactive sulfhydryl group was found to be located at Cys196 by amino acid sequence analysis of Nbs2-reactive peptides isolated by activated thiol-Sepharose covalent chromatography. Incubation of Mn-SOD in 1% SDS for 2 or 3 days at 25 degrees C or 5 min at 100 degrees C gave material showing two prominent components on polyacrylamide gel electrophoresis in the presence of 0.1% SDS. The major component had a molecular mass of 23 kDa; the other, 25 kDa. Reduction of the protein by dithiothreitol or 2-mercaptoethanol heated in SDS produced only the 25-kDa monomer species. Essentially, no thiol groups were detected in the 23 kDa form, in which two cysteine residues appear to have been oxidized to form an intrasubunit disulfide. This indicates that Cys196 has a reactive sulfhydryl and appears to be a likely candidate for a mixed disulfide formation in vivo. PMID- 2269297 TI - Immunological characterization of rapeseed myrosinase. AB - A purified 75-kDa myrosinase and a crude rapeseed myrosinase fraction were used as antigens to produce mouse anti-myrosinase monoclonal antibodies. The 75-kDa myrosinase was also used to produce a polyclonal rabbit antiserum. The antiserum and one monoclonal antibody reacted with three distinct rapeseed polypeptides of 75, 70 and 65 kDa (M75, M70 and M65, respectively). A second set of monoclonal antibodies reacted exclusively with the 75-kDa form of myrosinase, and a third set showed specificity towards two components of 52 and 50 kDa (myrosinase binding proteins, MBP52 and MBP50, respectively). MBP52 and MBP50 lack inherent myrosinase activity, but are nevertheless capable of mediating immunoprecipitation of myrosinase due to their interaction with myrosinase. Gel chromatography and glycerol gradient centrifugation experiments resolved two myrosinase-containing fractions. One of these had an approximate molecular mass of 140 kDa and consisted of disulfide-linked dimers of the 75-kDa myrosinase. The other fraction was heterogeneous in size with molecular masses ranging from 250 kDa to approximately 1 MDa. The high-molecular-mass fractions contained complexes consisting of disulfide-linked 70-kDa and 65-kDa myrosinases and non-covalently bound 52-kDa and 50-kDa myrosinase-binding proteins. PMID- 2269296 TI - Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. AB - Human rheumatoid synovial cells in culture secrete at least three related metalloproteinases that digest extracellular matrix macromolecules. One of them, termed matrix metalloproteinase 2 (MMP-2), has been purified as an inactive zymogen (proMMP-2). The final product is homogeneous on SDS/PAGE with Mr = 72,000 under reducing conditions. The NH2-terminal sequence of proMMP-2 is Ala-Pro-Ser Pro-Ile-Ile-Lys-Phe-Pro-Gly-Asp-Val-Ala-Pro-Lys-Thr, which is identical to that of the so-called '72-kDa type IV collagenase/gelatinase'. The zymogen can be rapidly activated by 4-aminophenylmercuric acetate to an active form of MMP-2 with Mr = 67,000, and the new NH2-terminal generated is Tyr-Asn-Phe-Phe-Pro-Arg Lys-Pro-Lys-Trp-Asp-Lys-Asn-Gln-Ile. However, following 4-aminophenylmercuric acetate activation, MMP-2 is gradually inactivated by autolysis. Nine endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, neutrophil elastase, cathepsin G, matrix metalloproteinase 3, and thermolysin) were tested for their abilities to activate proMMP-2, but none had this ability. This contrasts with the proteolytic activation of proMMP-1 (procollagenase) and proMMP-3 (prostromelysin). The optimal activity of MMP-2 against azocoll is around pH 8.5, but about 50% of activity is retained at pH 6.5. Enzymic activity is inhibited by EDTA, 1,10-phenanthroline or tissue inhibitor of metalloproteinases, but not by inhibitors of serine, cysteine or aspartic proteinases. MMP-2 digests gelatin, fibronectin, laminin, and collagen type V, and to a lesser extent type IV collagen, cartilage proteoglycan and elastin. Comparative studies on digestion of collagen types IV and V by MMP-2 and MMP-3 (stromelysin) indicate that MMP-3 degrades type IV collagen more readily than MMP 2, while MMP-2 digests type V collagen effectively. Biosynthetic studies of MMPs using cultured human rheumatoid synovial fibroblasts indicated that the production of both proMMP-1 and proMMP-3 is negligible but it is greatly enhanced by the treatment with rabbit-macrophage-conditioned medium, whereas the synthesis of proMMP-2 is constitutively expressed by these cells and is not significantly affected by the treatment. This suggests that the physiological and/or pathological role of MMP-2 and its site of action may be different from those of MMP-1 and MMP-3. PMID- 2269298 TI - A novel nitrilase, arylacetonitrilase, of Alcaligenes faecalis JM3. Purification and characterization. AB - A new type of nitrilase, arylacetonitrilase, has been purified from isovaleronitrile-induced cells of Alcaligenes faecalis JM3 in four steps. The purity of the enzyme was confirmed by SDS/polyacrylamide gel electrophoresis, ampholyte electrofocusing and double immunodiffusion in agarose. The enzyme has a molecular mass of about 275 kDa and consists of six subunits of identical molecular mass. The purified enzyme exhibits a pH optimum of 7.5 and a temperature optimum of 45 degrees C. The enzyme is specific for arylacetonitriles such as 2-thiophenacetonitrile, p-tolyacetonitrile, p-chlorobenzylcyanide, p fluorobenzylcyanide and 3-pyridylacetonitrile. The enzyme stoichiometrically catalyzes the hydrolysis of arylacetonitrile to arylacetic acid and ammonia, no formation of amide occurring. However, the enzyme does not attack nitrile groups attached to aromatic and heteroaromatic rings, which are hydrolyzed preferably by the nitrilases known previously. The enzyme requires thiol compounds such as dithiothreitol and 2-mercaptoethanol to exhibit its maximum activity. PMID- 2269299 TI - Different specificities of spleen tyrosine protein kinases for synthetic peptide substrates. AB - 20 synthetic peptides, each of which includes a tyrosyl residue flanked by either neutral or acidic amino acids in different proportions and at variable positions, have been employed as model substrates for investigation of the site specificity of three tyrosine protein kinases previously isolated from spleen [Brunati, A. M. & Pinna, L. A. (1988) Eur. J. Biochem. 172, 451-457] and conventionally termed TPK-I, TPK-IIB and TPK-III. Comparison of the phosphorylation efficiencies shows that each tyrosine protein kinase is considerably different from the others in both the stringency and the nature of its specificity determinants. By considering, in particular, the kinetic constants obtained with the pentapeptides AAYAA, EEYAA, AEYAA, EAYAA, with the tetrapeptides AYAA and EYAA and with the tripeptides AYA and EYA, it turns out that N-terminal acidic residue(s) are only essential with TPK-IIB for efficient phosphorylation with multiple residues displaying a synergistic effect. The very similar Km (130 microM) but 14-fold different Vmax values with YEEEEE vs. EEEEEY indicate that an N-terminal rather than C-terminal location of acidic residues is required for a high phosphorylation rate with, though not for binding to TPK-IIB. Acidic residues decrease the phosphorylation rate with TPK-I, a kinase related to the src family which is immunologically indistinguishable from the lyn TPK; they are nearly ineffective, however, with TPK-III, the least specific of the tyrosine protein kinases, which exhibits appreciable activity toward tripeptides and dipeptides like GAY and AY which are not significantly affected by TPK-I and TPK-IIB. While the peptide substrate specificity of TPK-I is similar to that of TPK-IIA, a spleen tyrosine protein kinase previously considered [Brunati, A. M., Marchiori, F., Ruzza, P., Calderan, A., Borin, G. & Pinna, L. A. (1989) FEBS Lett. 254, 145 149], the remarkable requirement of TPK-IIB alone for acidic peptides may suggest the involvement of this enzyme, which is also unique in its failure to autophosphorylate, in the phosphorylation of the highly conserved and quite acidic phosphoacceptor sites of the src family protein kinases. PMID- 2269300 TI - Large-scale preparation of T4 endonuclease VII from over-expressing bacteria. AB - Endonuclease VII is the product of gene 49 of phage T4 and was the first enzyme shown to resolve Holliday structures in vitro [Mizuuchi, K. et al. (1982) Cell 29, 357-365]. Low amounts of the enzyme were originally purified from phage infected cells [Kemper, B. & Garabett, M. (1981) Eur. J. Biochem. 115, 123-131]. We now report a purification procedure for milligram amounts of cloned endonuclease VII expressed in Escherichia coli with gene 49 under the control of a temperature-inducible promoter on a plasmid system [Tomaschewski, J. (1988) PhD Thesis, University of Bochum, FRG]. The protein was purified 500-fold from crude extracts in five steps with a recovery of 15%. The steps include (a) poly(ethyleneglycol)/dextran two-phase separation; (b) DEAE-cellulose; (c) single stranded DNA-agarose; (d) Mono-Q and (e) Mono-S chromatography. The final protein was more than 98% pure as estimated from SDS/PAGE analysis. The protein has an apparent molecular mass of 17.8 kDa on SDS-containing polyacrylamide gels and 36 kDa when determined by gel filtration or sedimentation through sucrose gradients in the presence of high salt (600 mM NaCl). In the absence of additional salt, the enzyme has a tendency to aggregate and products of molecular masses differing in steps of about 18 kDa appear on SDS-containing polyacrylamide gels. PMID- 2269301 TI - Purification and partial characterization of pyruvate decarboxylase from Oryza sativa L. AB - Pyruvate decarboxylase(PyrDC) was purified from rice bran to a specific activity of 1 mu kat/mg and partially characterized. The holoenzyme is a tetramer of two types of subunits with molecular masses 64 kDa and 62 kDa. Purified rice PyrDC exhibits positive cooperative kinetics with respect to pyruvate and functions with a significant lag phase. When compared to other plant PyrDC, the lag phase was shorter at low pyruvate concentrations and the S0.5 was smaller. The optimum pH (6.25) was also less acidic and the enzyme retained 30% of its maximal activity at neutral pH. In contrast to other plant PyrDC, rice PyrDC could be active at the onset of anoxia and would be activated by small changes in pyruvate concentration. PMID- 2269302 TI - Intracellular accumulation and oligosaccharide processing of alkaline phosphatase under disassembly of the Golgi complex caused by brefeldin A. AB - Electron microscopic observations showed that the fungal metabolite brefeldin A caused disassembly of the Golgi complex in human choriocarcinoma cells and accumulation of alkaline phosphatase (ALP) in the endoplasmic reticulum (ER) and nuclear envelope, where ALP was not apparently detectable in control cells. Pulse/chase experiments with [35S]methionine demonstrated that in the control cells, ALP synthesized as a 63-kDa precursor form was rapidly converted to a 66 kDa form, by processing of its N-linked oligosaccharides from the high-mannose type to the complex type, which was expressed on the cell surface after 30 min of chase. In contrast, in the brefeldin-A-treated cells the precursor was gradually converted to a 65-kDa form, slightly smaller than the control mature form, which was not expressed on the cell surface even after a prolonged time of chase. Kinetics of the ALP processing in the brefeldin-A-treated cells demonstrated that the precursor was initially converted to an intermediate form, partially sensitive to endo-beta-N-acetylglucosaminidase H (endo H), then to an endo-H resistant 65-kDa form. In addition, this form was found to be sensitive to neuraminidase digestion, though its sialylation was not so complete as that of the control mature form. Taken together, these results suggest that under disassembly of the Golgi complex caused by brefeldin A, oligosaccharide processing enzymes including sialyltransferase, an enzyme in the trans Golgi cisterna(e) and/or the trans Golgi network, might be redistributed into the ER and involved in processing of the oligosaccharides of ALP accumulating there. PMID- 2269303 TI - Citrate synthase from the thermophilic archaebacterium Thermoplasma acidophilium. Cloning and sequencing of the gene. AB - The gene encoding the citric acid cycle enzyme, citrate synthase, has been cloned from the thermoacidophilic archaebacterium, Thermoplasma acidophilum. We report the sequencing of this gene and its flanking regions, and the derived amino acid sequence of the enzyme is compared by multiple-sequence alignment analysis with those of citrate synthases from eubacterial and eukaryotic organisms. The similarity is less than 30% between the archaebacterial and non-archaebacterial sequences, although the majority of residues implicated in the catalytic action of the enzyme have been conserved across all three kingdoms. The cloned archaebacterial gene has been expressed in Escherichia coli to produce catalytically active citrate synthase. This is the first reported sequence of citrate synthase from the archaebacteria. PMID- 2269304 TI - Over-production, purification and properties of the uridine-diphosphate-N acetylmuramoyl-L-alanyl-D-glutamate: meso-2,6-diaminopimelate ligase from Escherichia coli. AB - The UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate ligase was over-produced and purified from two plasmid-harbouring strains of Escherichia coli. The first strain, E. coli JM83(pHE5), gave a 15-fold over-production relative to parental strain. The enzyme could be partially purified (8.8-fold) by ion-exchange chromatography. With the second strain, E. coli JM83(pMLD25), a very strong over-production was obtained, since the enzyme represented about 20% of the cytoplasmic proteins. Purification yielded 77% protein homogeneity. However, the enzymatic activity, which was very unstable, was lost during the purification procedure. Several properties of the enzyme were studied. The enzyme gave maximal activity around pH 8. The isoelectric point was 5.2. The activity was increased by potassium phosphate. Reverse and exchange reactions could be catalysed. The N terminal sequence of the protein was determined and correlated with the nucleotide sequence of the murE gene. The actual initiation codon was assigned. PMID- 2269305 TI - Purification and characterization of lipoamide dehydrogenase from Trypanosoma cruzi. AB - From Trypanosoma cruzi, the causative agent of Chagas' disease, a lipoamide dehydrogenase was isolated. The enzyme, an FAD-cystine oxidoreductase, shares many physical and chemical properties with T. cruzi trypanothione reductase, the key enzyme of the parasite's thiol metabolism. 1. From 60 g epimastigotic T. cruzi cells, 2.7 mg lipoamide dehydrogenase was extracted. The flavoenzyme was purified 3000-fold to homogeneity with an overall yield of 26%. 2. The enzyme is a dimer with a subunit Mr of 55,000. With 1 mM lipoamide (Km approximately 5 mM) and 100 microM NADH (Km = 23 microM), the specific activity at pH 7.0 is 297 U/mg. 3. With excess NADH, the enzyme is reduced to the EH2.NADH complex and, by addition of lipoamide, it is reoxidized, indicating that it can cycle between the oxidized state E and the two-electron-reduced state, EH2. 4. As shown by N terminal sequencing of the enzyme, 21 out of 30 positions are identical with those of pig heart and human liver lipoamide dehydrogenase. The sequenced section comprises the GGGPGG stretch, which represents the binding site for the pyrophosphate moiety of FAD. 5. After reduction of Eox to the two-electron reduced state, the enzyme is specifically inhibited by the nitrosourea drug 1,3 bis(2-chloroethyl)-1-nitrosourea (Carmustine), presumably by carbamoylation at one of the nascent active-site thiols. 6. Polyclonal rabbit antibodies raised against T. cruzi lipoamide dehydrogenase and trypanothione reductase are specific for the respective enzyme, as shown by immunoblots of the pure proteins and of cell extracts. PMID- 2269306 TI - Two genetically distinct methyl-coenzyme M reductases in Methanobacterium thermoautotrophicum strain Marburg and delta H. AB - Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in methanogenic archaebacteria. The reductase has been characterized in detail from Methanobacterium thermoautotrophicum strain Marburg and delta H, which grow on H2 and CO2 as energy source. During purification of the enzyme we have now discovered a second methyl-coenzyme M reductase (MCR II) in the two strains, which elutes at lower salt concentration from anion-exchange columns than the enzyme (MCR I) previously characterized. MCR II is similar to MCR I in that it is also composed of three different subunits alpha, beta, and gamma but distinct from MCR I in that the gamma subunit is 5 kDa smaller, as revealed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The N-terminal amino acid sequences of the alpha, beta, and gamma subunits of MCR II and MCR I were found to be different in several amino acid positions. The respective sequences showed, however, strong similarities indicating that MCR II was not derived from MCR I by limited proteolysis. The relative amounts of MCR I and MCR II present in the cells were affected by the growth conditions. When the cultures were supplied with sufficient H2 and and CO2 and the cells grew exponentially, essentially only MCR II was found. When growth was limited by the gas supply, MCR I predominated. PMID- 2269307 TI - Expression of human liver cytochrome P450 IIIA4 in yeast. A functional model for the hepatic enzyme. AB - Cytochrome P-450 (P450) NF, a member of the P450 IIIA subfamily, is the major contributor to the oxidation of the calcium-channel blocker nifedipine in human liver microsomes. A cDNA clone designated NF25 encoding for human P450 NF was isolated from a bacteriophage lambda gt11 expression library [Beaune, P. H., Umbenhauer, D. R., Bork, R. W., Lloyd, R. S. & Guengerich, F. P. (1986) Proc. Natl Acad. Sci. USA 83, 8064-8068]. We have expressed NF25 cDNA in Saccharomyces cerevisiae using an expression vector constructed from pYeDP1/8-2 [Cullin, C. & Pompon, D. (1988) Gene 65, 203-217]. Yeast transformed with the plasmid containing the NF25 sequence (pVNF25) showed a ferrous-CO spectrum typical of cytochrome P-450. Microsomal preparations contained a protein with an apparent molecular mass identical to that of P450-5 (a form isolated from human liver indistinguishable from P450 NF) that was not present in microsomes from control yeast (transformed with pYeDP1/8-2 alone), as revealed by immunoblotting with anti-P450-5 antibodies. On the other hand, antibodies raised in rabbits against human liver P450 IIC8-10 and rat liver P450 IA1 and P450 IIE1 did not recognize yeast-expressed P450 NF25. The P450 NF25 content in microsomes was about 90 pmol/mg protein. Microsomal, yeast-expressed P450 NF25 exhibited a high affinity for different substrates including macrolide antibiotics, dihydroergotamine and miconazole as shown by difference visible spectroscopy. Microsomal suspensions containing P450 NF25 were also able to catalyze several oxidation reactions that were expected from the activities of the protein isolated from human liver, including nifedipine 1,4-oxidation, quinidine 3-hydroxylation and N-oxygenation, and N-demethylation of the macrolide antibiotics erythromycin and troleandomycin. The yeast endogenous NADPH-cytochrome P-450 reductase thus couples efficiently with the heterologous P450 NF25 though its level is far lower than that of its ortholog in human liver. Indeed addition of rabbit liver NADPH-cytochrome P-450 reductase increased the oxidation rates. Rabbit liver cytochrome b5 also caused a marked enhancement of catalytic activities, as had been noted previously for this particular P450 enzyme in a reconstituted system involving the protein purified from human liver. Furthermore, the level of the yeast endogenous cytochrome P-450 (lanosterol 14-demethylase) has been found to be negligible compared to the heterologously expressed cytochrome P-450 (30 times less). Thus, yeast microsomes containing P450 NF25 constitute by themselves a good functional model for studying the binding capacities and catalytic activities of this individual form of human hepatic cytochrome P-450. PMID- 2269308 TI - A highly active and oxidation-resistant subtilisin-like enzyme produced by a combination of site-directed mutagenesis and chemical modification. AB - The subtilisins are known to be susceptible to chemical oxidation due to the conversion of Met222 into the corresponding sulfoxide. A number of derivatives with resistance towards oxidation have previously been prepared by replacement of this group with the other 19 amino acid residues. Unfortunately, the activities of these enzymes were of the order of 1-10% of that obtained with the wild-type enzyme. In contrast, the oxidation-labile cysteine mutant exhibited much higher activity, suggesting that this is associated with the presence of a sulphur atom in the amino acid at position 222. It is shown here that it is possible to maintain a sulphur atom in the amino acid at position 222 without the enzyme becoming labile towards oxidation. A subtilisin from Bacillus lentus, subtilisin 309, in which Met222 was replaced with a cysteinyl residue by site-directed mutagenesis was modified with thioalkylating reagents. Treatment of such enzyme derivatives with H2O2 revealed that their stabilities towards oxidation had increased significantly compared to both wild-type and unmodified [Cys222]subtilisin. One of the chemically modified enzyme derivatives, [Me-S Cys222]subtilisin, exhibited a kcat/Km value of 56% of that obtained with the wild-type enzyme when assayed against the substrate Suc-Ala-Ala-Pro-Phe-NH-Ph-NO2 (Suc, succinyl) and it exhibited 89% activity when tested in an assay with dimethyl casein as a substrate. The corresponding values obtained for unmodified [Cys222]subtilisin were lower, i.e. 39% for the dimethyl casein activity and 46% for the kcat/Km for the hydrolysis of Suc-Ala-Ala-Pro-Phe-NH-Ph-NO2. This demonstrates the feasibility of replacing the oxidation-labile methionyl residue group in a subtilisin enzyme with a group stable towards oxidation without substantially reducing the activity. PMID- 2269310 TI - Infrared spectroscopy of phytochrome and model pigments. AB - Fourier-transform infrared difference spectra between the red-absorbing and far red-absorbing forms of oat phytochrome have been measured in H2O and 2H2O. The difference spectra are compared with infrared spectra of model compounds, i.e. the (5Z,10Z,15Z)- and (5Z,10Z,15E)-isomers of 2,3,7,8,12,13,17,18-octaethyl bilindion (Et8-bilindion), 2,3-dihydro-2,3,7,8,12,13,17,18-octaethyl-bilindion (H2Et8-bilindion), and protonated H2Et8-bilindion in various solvents. The spectra of the model compounds show that only for the protonated forms can clear differences between the two isomers be detected. Since considerable differences are present between the spectra of Et8-bilindion and H2Et8-bilindion, it is concluded that only the latter compound can serve as a model system of phytochrome. The 2H2O effect on the difference spectrum of phytochrome supports the view that the chromophore in red-absorbing phytochrome is protonated and suggests, in addition, that it is also protonated in far-red-absorbing phytochrome. The spectra show that protonated carboxyl groups are influenced. The small amplitudes in the difference spectra exclude major changes of protein secondary structure. PMID- 2269309 TI - A new force-field program for the calculation of glycopeptides and its application to a heptacosapeptide-decasaccharide of immunoglobulin G1. Importance of 1-6-glycosidic linkages in carbohydrate.peptide interactions. AB - Energetically favored conformations of glycopeptide 1 were calculated using the newly developed force-field program, GEGOP (geometry of glycopeptides). The three dimensional structure of glycopeptide 1, which is part of the Fc fragment of IgG1, has been calculated. 1 contains 27 amino acid residues from Pro291 to Lys317 and a biantennary decasaccharide N-linked to Asn297. The conformations of the peptide and the carbohydrate parts are shown to be mutually dependent. Single glycosyl residues of 1 exhibit interaction energies of up to -31.8 kJ/mol with the peptide portion. Generally, only a few of the glycosyl residues of the oligosaccharide moiety express significant interaction energies with the peptide part. No easy prediction is possible of glycosyl residues which exhibit favorable interaction energies. However, in all of the calculated structures, the glycosyl residues of the 1-6-linked branches show strong attractive forces for the peptide part. 1-6-glycosidically linked branches can adopt a larger number of conformations than other linkages due to their high flexibility which allows more favorable interactions with proteins. We developed the GEGOP program in order to be able to study the preferred conformations of large glycopeptides. The program is based on the GESA (geometry of saccharides) program and utilizes the HSEA (hard sphere exo anomeric) force field for the carbohydrate part and the ECEPP/2 (empirical conformation energy program for peptides) force field [Nemethy, G., Pottle, M. S. & Scheraga, H. A. (1983) J. Phys. Chem. 87, 1883-1887] for the peptide part. The GEGOP program allows the simultaneous relaxation of all rotational degrees of freedom of these glycoconjugates during the energy optimization process. Thus, mutual interactions between glycosyl and amino acid residues can be studied in detail. PMID- 2269311 TI - Reaction pathways for biodehalogenation of fluorinated anilines. AB - Pathways for biodehalogenation of fluorinated aniline derivatives were investigated. Microsomal NADPH-dependent dehalogenation of fluoroanilines was shown to proceed by three different reaction pathways. The first route appeared to result in monooxygenation at a fluorinated position and release of the fluorine atom as a fluoride anion. The primary additional reaction product formed is the reactive quinoneimine, not the 4-hydroxyaniline. In NADPH-containing microsomal systems with 4-fluoro-substituted anilines, formation of the 4 hydroxyaniline derivative is observed because NADPH chemically reduces this quinoneimine metabolite. A second pathway for dehalogenation proceeds by protein binding of a fluoro-containing (semi)quinoneimine metabolite, the formation of which may result from the mono-oxygenase reaction (pathway 1) and/or from (re)oxidation of a hydroxyaniline metabolite by superoxide anion radicals produced by the microsomal system. This latter reaction pathway becomes more important with increasing number of fluoro-substituents in the fluoroaniline derivative. The higher ratio of fluoride anion formed to 4-hydroxyaniline derivative detected in incubations with liver microsomes from dexamethasone treated rats, as compared to incubations with liver microsomes from control rats, can in part be explained by the higher production of superoxide anion radicals observed in the dexamethasone systems. The third mechanism was shown to proceed by formation of a hydroxylated metabolite that loses fluoride anion upon exposure to oxygen. The reactive intermediate formed upon oxygen exposure might be the semiquinoneimine which loses its fluorine atom as a fluoride anion upon dimerization or polymerization and/or protein binding. The fluorohydroxyanilines, in which the hydroxyl group is ortho or para with respect to the fluoro substituent, appear especially to be highly unstable and lose fluoride anion in the presence of oxygen. Finally, it is concluded that all three pathways for dehalogenation of fluorinated aniline derivatives are bioactivation pathways. The reactivity of the (semi)quinoneimines formed in these reactions is dependent on their substitution pattern and increases with increasing number of fluoro substituents. Therefore, bioactivation for a series of fluorinated aniline derivatives, can be expected to vary with the substitution pattern and to increase with increasing number of halogen substituents. PMID- 2269312 TI - Neurological presentation of neuro-Behcet's syndrome: clinical categories. AB - In an attempt to categorize the diverse neurological manifestations of Behcet's syndrome, a group of 10 patients was prospectively studied; the diagnosis of Behcet's syndrome was not known in any of them prior to their neurological presentation. A reasonably clear distinction can be made to divide the manifestations into three general categories with some overlap. Category I includes patients with increased intracranial pressure with or without cerebral venous sinus thrombosis. Category II are those presenting with a stroke. Category III are those patients who present with spinal cord involvement and CSF pleocytosis. Brainstem involvement was noted independently of the group. In general, patients with Neuro-Behcet's syndrome showed little ocular involvement. The course of the illness both in morbidity and mortality tended to be better in category I, and mortality was only seen in category II patients. In populations susceptible to the disease, the clinical categorisation proposed may alert the clinician to the possibility of neuro-Behcet's syndrome whenever patients with pseudotumour cerebri, dural sinus thrombosis, stroke in the young, unexplained myelitis or possible multiple sclerosis are encountered. PMID- 2269313 TI - Primary cerebral abscess due to nocardia presenting as 'ghost tumor'. Clinical and pathological study. AB - We report a case of a primary cerebral abscess due to Nocardia asteroides in a nonimmunocompromised patient with a particular clinical course. The first symptom (right subacute brachial palsy) and the lesion in a computed tomographic (CT) scan (left parietofrontal edema suggestive of brain tumor) disappeared after corticosteroid treatment and the patient was discharged with total recovery. After 2 months she complained of headache and visual disturbance. A new CT scan showed an annular lesion in the left occipital lobe. A cerebral biopsy was diagnosed of nocardia infection. The patient died 2 weeks after this biopsy. A postmortem study showed an occipital brain abscess but not structural abnormalities were seen in the left parietofrontal area. We believe that the first episode could be a local inflammatory response to cerebral implantation of nocardia which disappeared clinically in the CT scan and in the postmortem study after corticosteroid treatment. Then the nocardia could have displaced by the hematological route to the second and definitive cerebral lesion. PMID- 2269314 TI - Serial magnetic resonance imaging studies with paramagnetic contrast medium: assessment of disease activity in patients with multiple sclerosis before and after influenza vaccination. AB - Eleven patients with a relapsing-remitting form of multiple sclerosis (MS) were examined clinically and with magnetic resonance imaging scans 3 weeks before, at the day of vaccination with killed influenza virus and 3 weeks afterwards. No exacerbations were noted in the pre- or postvaccination period. Eight contrast enhanced or active lesions were present at the onset of the study. Three new active lesions appeared at the end of the prevaccination period while only 1 new active lesion was found at the end of the postvaccination period. We conclude that vaccination with killed influenza virus has no clinical or subclinical short term effect on the activity of MS. PMID- 2269315 TI - Efficient treatment of neurogenic bladder disorders in multiple sclerosis with initial intermittent catheterization and ultrasound-controlled training. AB - Out of 350 multiple sclerosis (MS) patients, 197 had residual urine (RU), on average 113 ml on admission. Treatment with initial intermittent catheterisation and bladder training normalized the neurogenic bladder disorders (NBD) in most patients; the RU was 28 ml on average at discharge. Continence improved with the reduction of RU. Even in those 37 patients with a RU of over 200 ml on admission, this management reduced the average RU to 83 ml on discharge. Patients with a RU of over 50 ml had bacteriuria 3 times more often than patients with a lower RU. In patients admitted with a long-term catheter, the catheter was removed; these patients had an average RU of 166 ml on admission, 23 ml on discharge. There was a highly significant correlation between high RU and the degree of cerebral atrophy. Patients with more than 50 ml RU at discharge were those with severe cerebral atrophy, tetraplegia and dementia. The different patterns of NBD were merely different states of the same NBD under different training conditions. Since NBD occurs about a 1,000 times more often than bowel incontinence with the same lesions in MS, it is not the cerebrospinal lesions per se, but the peripheral vicious circle they trigger, which leads to detrusor hyperactivity and dyssynergy. The peripheral pathogenetic mechanism is urinary retention leading to bladder overextension. Urodynamic investigations beyond the measurement of RU (by ultrasound) are not necessary for the treatment of NBD in most MS patients. The noninvasive and inexpensive therapy described here is effective. PMID- 2269316 TI - Stuttering as a manifestation of right-hemispheric subcortical stroke. AB - A right-handed man developed stuttering, without aphasia, as a result of a circumscribed subcortical infarction in the right hemisphere. He never stuttered before and has no family history of stuttering. Damage to callosal pathways coordinating the activity of both hemispheres during speech is proposed as a possible explanation for the stuttering. PMID- 2269318 TI - Hemiballism as a presentation of a meningioma. AB - A 73-year-old woman with a meningioma presented with hemiballism. This is the report of an unusual presentation of a primary brain tumor. PMID- 2269317 TI - Generalized dystonia with bilateral striatal computed-tomographic lucencies in a patient with human immunodeficiency virus infection. AB - We report the case of a 36-year-old, drug-addicted woman with laboratory evidence of human immunodeficiency virus infection in the central nervous system. The patient presented with generalized dystonia involving both axial and segmental muscles, mainly in the legs, and with minimal additional neurological abnormalities. A computed-tomographic scan revealed bilateral and symmetrical lucencies in the putaminal region. The possibility of an acquired immunodeficiency syndrome-related manifestation is discussed. PMID- 2269319 TI - Fulminant myasthenia gravis soon after initiation of acebutolol therapy. AB - We report the case of myasthenia gravis in a 74-year-old woman, 2 weeks after acebutolol had been introduced as the sole treatment for systemic hypertension. The disease developed at a fulminant and fatal course despite drug withdrawal. The possibilities of coincidental association between the two events, triggering of a preexisting latent myasthenia gravis or full induction of the disease by acebutolol, are discussed. PMID- 2269320 TI - Neurosarcoidosis presenting as benign intracranial hypertension. AB - A patient who on presentation fulfilled diagnostic criteria for benign intracranial hypertension subsequently developed a lymphocytic meningitis. A final diagnosis of neurosarcoidosis was made and the patient responded well to oral steroids. PMID- 2269321 TI - The influence of temperature on somatosensory-evoked potentials during cardiopulmonary bypass. AB - Somatosensory-evoked potentials (SEPs) after median nerve stimulation were recorded in 10 neurologically normal patients during cardiopulmonary bypass and hypothermia. In all patients the changes of the latencies (spinal N13, cortical N20 and N35) and the central conduction time during cooling, and the decrease in latencies during rewarming was described by a gamma function. The analytic discussion of pooled data of all patients led to another SEP-latency-temperature relationship than the observation of each single patient. In 6 of 10 patients there was found a maximum of latency increase before the minimal temperature was reached. The cooling and the rewarming curve had to be considered separately. Latency changes of SEPs during hypothermia are discussed as a very complex phenomenon influenced by many technical and patient factors. This reduces the value of SEPs as an index of central nervous system integrity during open heart surgery and hypothermia. PMID- 2269322 TI - Regional cerebral blood flow study with 99mTc-hexamethyl-propyleneamine oxime single photon emission computed tomography in Alzheimer's and multi-infarct dementia. AB - Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia. PMID- 2269323 TI - Intrathecal synthesis of virus antibodies: a diagnostic test for multiple sclerosis. AB - Intrathecally synthesized antibodies against measles and rubella were determined in 221 patients with multiple sclerosis (MS) and in 476 control cases. A local production was detectable in more than 80% of the MS cases but in none of the control group. These results show that the demonstration of intrathecally synthesized antibodies against neurotropic viruses not related with respective infections may serve as helpful test in the diagnosis of MS. PMID- 2269324 TI - Autoimmune T cell recognition of human acetylcholine receptor: the sites of T cell recognition in myasthenia gravis on the extracellular part of the alpha subunit. AB - Autoimmune T cell lines were prepared from peripheral blood lymphocytes of five myasthenia gravis patients by passage in vitro with an equimolar mixture of 18 overlapping synthetic peptides corresponding to the entire extracellular region (residues alpha 1-210) of the alpha subunit of human acetylcholine receptor (AChR). The proliferative responses of the human AChR-specific T cell lines to each of the individual peptides were determined. It was found that the profiles of the peptides recognized by the T cells were different among the five T cell lines, consistent with genetic control operating at the recognition site level. However, other regulatory influences may play important roles in the triggering of the autoimmune responses. These results suggest that the pathogenesis of this autoimmune disease is variable at the cellular-molecular level. PMID- 2269325 TI - Immunological heterogeneity of autoreactive T lymphocytes against the nicotinic acetylcholine receptor in myasthenic patients. AB - The response of human T lymphocytes against the nicotinic acetylcholine receptor (AChR) was studied in five patients with myasthenia gravis (MG) and in six healthy donors using either native Torpedo AChR or recombinant protein derived from the mammalian AChR alpha subunit (X4, residues 6-216 of mouse AChR alpha subunit). The present study demonstrates that (a) AChR-specific T helper cell lines can be generated from MG patients [either from peripheral blood lymphocytes (PBL) or from thymocytes] as well as from PBL of normal controls, (b) lymphocytes from MG patients, but not from controls, recognize the mammalian AChR but not the Torpedo receptor, (c) in humans, the HLA-DR2-associated T cell epitope is probably located in the region of residues 162-216 of the AChR alpha subunit and (d) there is a considerable heterogeneity of autoreactive T cell responses: (i) T cell lines from different HLA-type donors have distinct epitope profiles; (ii) the epitope specificity of the PBL-derived T cell line is different from that of the thymocyte-derived line; (iii) the epitope specificities of patient-derived T cell lines are different from those generated from normal controls who share the same HLA phenotype. PMID- 2269326 TI - Evidence of IgG-mediated enhancement of the antibody response in vivo without complement activation via the classical pathway. AB - The complement (C) dependency of IgG-mediated enhancement of the antibody response was investigated by immunizing mice with trinitrophenyl-coupled keyhole limpet hemocyanin (TNP-KLH) and either a C-activating TNP-specific monoclonal IgG2a antibody (Hy-1.2) or a mutant, non-C-activating variant of Hy-1.2 (M12). Hy 1.2 as well as M12 efficiently enhanced the anti-KLH response, although Hy-1.2 was more active. In addition, also a naturally non-C-activating TNP-specific IgG1 antibody enhanced the response to TNP-coupled bovine serum albumin. Moreover, C activating IgG could enhance the antibody response in mice depleted of C3 by treatment with cobra venom factor. These findings suggest that the classical pathway of C activation is not required for IgG-mediated enhancement. PMID- 2269327 TI - Cyclosporin A inhibits the interleukin 2 receptor alpha chain gene transcription but not its cell surface expression: the alpha chain stability can explain this discrepancy. AB - The effect of the immunosuppressor cyclosporin A (CsA) on the expression of interleukin (IL) 2 receptors was investigated in a human T cell line IARC301 which constitutively expresses such receptors. This cell line also spontaneously secretes IL2 which supports its autocrine growth. We have previously shown that CsA prevents the constitutive transcription of the IL2 gene in these cells. Here we show that as soon as 4 h after CsA addition, the transcription of the gene encoding the alpha chain (p55) of IL2R was inhibited. IL2 can transiently increase the expression of this gene. CsA did not prevent this transient IL2 dependent induction of IL2R alpha, but could still partially inhibit it. Once IL2 induction was over, CsA exerted its full inhibition. Thus, CsA does not seem to inhibit IL 2R alpha gene transcription simply by inhibition of IL2 synthesis. However, no modification of IL2R alpha expression on the cell surface could be detected after 48 h in the presence of CsA. This discrepancy between the effect of CsA on IL2R alpha expression as probed at the mRNA or the protein level can be accounted for by the stability of the IL2R alpha protein after synthesis. Indeed, the half-life of IL2R alpha chain is longer than 40 h. This suggests that the alpha chain, after it is endocytosed together with the beta chain as a component of high-affinity IL2R, might recycle back to the cell surface. PMID- 2269328 TI - Processing without proteolytic cleavage is required for recognition of insulin by T cells. AB - Beef insulin as well as a chymotryptic A-chain fragment [BI-A1-14(SSO3-)3] need uptake by antigen-presenting cells (APC) for efficient presentation in combination with major histocompatibility complex class II molecules to insulin specific T cells. This could be shown by the inability of aldehyde-fixed APC to present these antigens to T cells. Furthermore, presentation of the insulin fragment as well as presentation of ovalbumin (OVA) was inhibited by treatment of APC with chloroquine, cerulenin or tunicamycin. This was not the case for a processing-independent OVA peptide. Treatment of APC during antigen pulsing with various protease inhibitors, active on all classes of proteases, did not block presentation of insulin although some of these reagents did interfere with the presentation of OVA. Several inhibitors especially of serine or thiol proteases rather enhanced the presentation of insulin. This indicates that intracellular proteolytic cleavage of insulin does not seem to be required for generation of the antigenic determinant but, if it occurs, rather destroys the antigenic peptide. Insulin and its A-chain fragment may, therefore, represent a model for a processing-dependent antigen not requiring proteolytic cleavage but other modifications. PMID- 2269329 TI - Mycobacterial-induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients. AB - Little information is available about the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. To address this we have developed a cytotoxicity assay in which 51Cr-labeled monocytes pulsed with bacillus Calmette Guerin (BCG) or Mycobacterium leprae, were used as target cells in overnight cytotoxicity assays. As effector cells, peripheral blood mononuclear cells from healthy occupational contacts or from leprosy patients stimulated with antigen for 7 days were used. Cytotoxicity against antigen-pulsed monocytes that could be induced by mycobacterial antigens was proportional to the degree of antigen responsiveness in each individual, as measured in lymphocyte transformation tests. The lepromatous leprosy patients tested were often poor responders to BCG as well as M. leprae, both with regard to induction of cytotoxicity as well as in lympho proliferation. Killing was significantly higher against antigen-pulsed vs. nonpulsed monocytes, although significant killing was induced against the latter as well and paralleled by induction of natural killer activity against the K-562 target cell. Cross-reactivity was observed between BCG and M. leprae, but not with unrelated antigen (tetanus toxoid) or with endogenous stress proteins induced by heat shock. M. leprae- and BCG-activated cytotoxic cells were found in both the CD4-CD8+ and CD4+CD8- populations, whereas in contrast the soluble antigen, purified protein derivative of M. tuberculosis, generated cytotoxic cells that were exclusively of the CD4+ phenotype. The involvement of both specific T cells as well as nonspecific cells in the killing of human macrophages may be important with respect to protection and immunopathology induced by mycobacterial antigens. PMID- 2269330 TI - Retroviral interleukin 5 gene transfer into interleukin 5-dependent growing cell lines results in autocrine growth and tumorigenicity. AB - Two interleukin 5 (IL5)-specific retroviral expression vectors have been constructed containing the neomycin gene as selectable marker and either the mouse IL5 cDNA region or the rat genomic IL5 gene under the control of the thymidine kinase promoter. High viral titer supernatants derived from the transfected or infected packaging cell line psi 2 were used to infect the two cell lines B13 and T88M whose growth is dependent on exogenous IL 5. Infection resulted in G418 resistance and IL 5-independent growth with a high frequency. Clones were established which secrete between 2 and greater than 1000 U IL5. The proliferation of the IL5 autocrine growing cells could be inhibited by an antibody directed against the IL5 receptor indicating that they grow as a result of the endogenously produced IL5. Regardless of the amount of IL5 they produced, all of the clones were highly tumorigenic in nucle mice. The phenotype of the tumors was indistinguishable from that of the injected cells. T88M or B13 cells infected with a control virus neither produced IL5, nor became factor independent, nor produced tumors. Together, the IL5 gene transfer and expression into IL5-dependent growing cells are in accordance with the "autocrine growth" hypothesis and contrast analogous experiments with IL4. PMID- 2269331 TI - Isolation and characterization of IgG2a-reactive autoantibodies from influenza virus-infected BALB/c mice. AB - Repeated influenza virus infection induces the production of dominantly IgG2a type virus-specific antibodies as well as the appearance of IgG2a-reactive autoantibodies in BALB/c mice characterized by low spontaneous rheumatoid factor type autoantibody production. IgG2a-reactive autoantibody-producing hybridomas could be isolated from the spleen of influenza virus-infected BALB/c mice. The mAb produced by these clones represent not only IgM but also IgG and IgA isotypes and show strong isotype or isoallotype specificity. The common functional property of these autoantibodies is their preferential- and high-affinity binding to complexed, solid-phase-bound or heat-aggregated IgG2a when compared to native soluble or cell-bound IgG2a. The mechanism of induction and the possible biological function of these autoantibodies are discussed in the light of their fine specificity and functional properties. PMID- 2269332 TI - A novel thymic epithelial adhesion molecule. AB - Interactions between thymocytes and thymic stromal cells are responsible for positive and negative selection of T cell, their differentiation, maturation and proliferation. The signals required for these events to occur often necessitate close contact, and indeed adhesion, between the cell types involved. The identification of specific adhesion molecules in this context, is, therefore, a vital first step in determining the nature of the signal they mediate or facilitate at a given stage of differentiation. In the present work we identify, isolate and partially characterize a ligand present on thymic medullary epithelial cells which selectively binds CD4+ CD8+ thymocytes found primarily in the thymic cortex. This adhesion molecule is composed of two non-covalently associated glycoproteins of 23 kDa and 45 kDa, respectively, both of which are needed to bind to thymocytes. The importance of the finding is that the ligand, in isolated immobilized form, binds the same thymocyte subset as the original epithelial cell line from which it was isolated. The CD4+ CD8+ thymocyte subset is the precursor of single-positive mature T cells; hence the putative biological activity of the ligand in question takes place at a pivotal stage of T cell differentiation. PMID- 2269333 TI - Identification of two distinct phosphoproteins as components of the human B cell antigen receptor complex. AB - In human B cells, the molecules that, upon receptor occupancy, couple membrane immunoglobulin to intracellular signal transduction pathways have never been identified. We here describe two phosphoproteins as integral parts of the B cell antigen receptor complex. Membrane IgM is non-covalently associated with a disulfide-linked heterodimer of glycoproteins. These molecules can be demonstrated on B cell lines and freshly isolated polyclonal B cell populations and are subject to phosphorylation at serine residues. Identification of these constituents of the B cell receptor complex opens up the opportunity to study coupling of the B cell antigen receptor to the intracellular signal transduction machinery at the molecular level. PMID- 2269334 TI - Identification of the genes encoding the IgM-alpha and Ig-beta components of the IgM antigen receptor complex by amino-terminal sequencing. AB - Beside the immunoglobulin (Ig) heavy and light chains the murine B cell receptor of the IgM class contains a heterodimer of two transmembrane proteins (IgM-alpha and Ig-beta). By N-terminal sequencing of IgM-alpha and Ig-beta we have identified the genes encoding these proteins as mb-1 and B29, respectively. Both genes are B cell specific and have been previously cloned from B minus T cell subtractive cDNA libraries. We have constructed expression vectors of the two genes and demonstrate that expression of the mb-1 and B29 genes can influence the surface expression of IgM in micron-transfected myeloma cells. From the known sequences of the IgM-alpha and Ig-beta proteins and from the results of previous transfection experiments with various vectors expressing the mu chain we have developed a structural model of the B cell antigen receptor of class IgM which we compare with that of the T cell antigen receptor. PMID- 2269335 TI - The new model of DNA structures. AB - The new model of the DNA dynamic state is proposed in terms of Watson-Crick (WC) and Corey-Pauling-Kortum (CPK) models by the modification of the cis ladder conformation. The model may rationally explain the DNA replication, transcription, renaturation, hybridization, premelting and breach etc. PMID- 2269336 TI - The oral hypoglycemic agent, U-56324, inhibits the activity of ATP-sensitive potassium channels in cell-free membrane patches from cultured mouse pancreatic B cells. AB - U-56324, a hypoglycemic agent derived from nicotinic acid, inhibited the activity of ATP-sensitive potassium channels in excised patches from mouse pancreatic B cells. The effect of U-56324 on channel activity was reversible and concentration dependent while it had no effect on single channel conductance. The positional isomer, U-59588, which has relatively little hypoglycemic activity, had no effect on channel properties. U-56324, at the same concentrations, had no effect on calcium-activated potassium channels. The basis for the potentially antidiabetic properties of U-56324 may therefore be due to direct and specific inhibition of ATP-sensitive potassium channels. PMID- 2269337 TI - NaF and mononucleotides as inhibitors of 3'-5'-exonuclease activity and stimulators of polymerase activity of E. coli DNA polymerase I Klenow fragment. AB - It has been shown that, in the absence of dATP in the poly(dT).oligo(dA) template primer complex, the rate of primer cleavage by the E. coli DNA polymerase I Klenow fragment equals 4% of polymerization rate, while in the presence of dATP it equals as much as 50-60%. NaF and NMP taken separately inhibit exonuclease cleavage of oligo(dA) both with and without dATP. The addition of NaF (5-10 mM) or NMP (5-20 mM) increases the absolute increment of polymerization rate 5-9-fold relative to the absolute decrement of the rate of nuclease hydrolysis of primer. This proves the assumption that not more than 10-20% of primer molecules, interacting with the exonuclease center of polymerase, are cleaved by the enzyme. Presumably, NaF and nucleotides disturb the coupling of the 3'-end of oligonucleotide primer to the exonuclease center of the enzyme. As the primers mostly form complexes with the polymerizing center, the reaction of polymerization is activated. PMID- 2269338 TI - Stimulation of actin synthesis in phalloidin-treated cells. Evidence for autoregulatory control. AB - We used the technique of scrape loading to introduce phalloidin into mouse embryo fibroblasts in mass culture. Phalloidin almost completely destroyed actin microfilament bundles, but the amount of polymerized cytoskeleton-associated actin was increased approximately two-fold and the amount of monomeric (Triton X 100 extractable) actin was significantly reduced. The major result of the present study is that the rate of actin synthesis in the phalloidin-treated cells was 2-3 times higher than in the control cells. Northern blot and translation in a cell free system from rabbit reticulocytes showed that the actin mRNA level significantly increased as a result of phalloidin treatment. PMID- 2269339 TI - Detection of covalent enzyme-substrate complexes of nitrilase by ion-spray mass spectroscopy. AB - Nitrilase from Rhodococcus ATCC 39484 was found to consist of two species of Mr 40,258 +/- 2 and 40,388 +/- 2 Da. When the enzyme was incubated with nitrile substrates and the reaction quenched with acid, higher Mr species were observed. The mass differences were consistent with addition of a substrate molecule to each species. These results represent the first reported demonstration that this, or any other nitrilase forms a covalent intermediate with its substrates. The observation that the intermediate, suggested to be either a thioimidate or an acylenzyme, can be trapped by acidification indicates that the rate of breakdown of the intermediate is rate-limiting. PMID- 2269340 TI - Class IV mammalian alcohol dehydrogenase. Structural data of the rat stomach enzyme reveal a new class well separated from those already characterized. AB - The stomach form of alcohol dehydrogenase has been structurally evaluated by peptide analysis covering six separate regions of the rat enzyme. Overall, this new structure differs widely (32-40% residue differences) from the structures of three classes of alcohol dehydrogenase characterized before from the same species. Consequently, this novel enzyme constitutes a true fourth class of mammalian alcohol dehydrogenase. In particular, differences are extensive also towards class II, although enzymatic and physicochemical properties initially suggested overall similarities with class II. The new structure establishes the presence of one further alcohol dehydrogenase mammalian gene, extends the enzyme family derived from repeated gene duplications, and confirms tissue-specific expressions. PMID- 2269341 TI - Iron detoxifying activity of ferritin. Effects of H and L human apoferritins on lipid peroxidation in vitro. AB - Three recombinant human apoferritin variants were added to ferrous iron and the amount of lipid peroxidation produced by hydrogen peroxide was studied. The H apoferritin had the strongest inhibitory effect on lipid peroxidation, probably due to its ferroxidase activity. The L-apoferritin inhibited lipid peroxidation slowly and only at neutral pH. The H-mutant 91, deleted of the last 22 C-terminal amino acids, and which is not able to form an iron core, had minimal effects on iron lipid peroxidation. It was concluded that both ferro-oxidase and iron mineralization activities are necessary for ferritin iron detoxifying action. PMID- 2269342 TI - Effect of ADP/ATP antiporter conformational state on the suppression of the nonspecific permeability of the inner mitochondrial membrane by cyclosporine A. AB - The influence of the conformational state of ADP/ATP antiporter on the efficiency of the inhibitory effect of cyclosporine A on the Ca2(+)-induced nonspecific permeability of the inner mitochondrial membrane has been studied. Carboxyatractiloside, the inhibitor of ADP/ATP-antiporter, was shown to prevent the cyclosporine A-induced suppression of the nonspecific permeability. The carboxyatractiloside effect was displayed only in mitochondria depleted of adenine nucleotides. Bifunctional SH reagent, phenylarsine oxide, was also able to reverse the effect of cyclosporine A. The data are consistent with the suggestion that cyclosporine A causes suppression of the nonspecific permeability due to its effect on the ADP/ATP antiporter conformation. PMID- 2269343 TI - Interaction of smooth muscle caldesmon with phospholipids. AB - Taking into account the perimembrane localization of caldesmon [(1986) Nature 319, 68] and its ability to participate in the regulation of receptor clusterization [(1989) J. Biol. Chem. 264, 496], we studied the interaction of duck gizzard caldesmon with soybean phospholipids (azolectin). By using four independent methods, i.e. light scattering, gel-electrophoresis, gel-filtration and ultracentrifugation, we showed a Ca-independent complex formation between caldesmon and azolectin. Interacting with caldesmon, calmodulin is shown to dissociate the caldesmon-azolectin complex. It is supposed that the caldesmon phospholipid interaction may affect caldesmon phosphorylation by Ca-phospholipid dependent protein kinase. This effect may be important for various cell motility processes. PMID- 2269344 TI - The reactivity of hydrazine with photosystem II strongly depends on the redox state of the water oxidizing system. AB - The decay kinetics of the redox states S2 and S3 of the water-oxidizing enzyme have been analyzed in isolated spinach thylakoids in the absence and presence of the exogenous reductant hydrazine. In control samples without NH2NH2 a biphasic decay is observed. The rapid decline of S2 and S3 with YD as reductant exhibits practically the same kinetics with t1/2 = 6-7 s at pH = 7.2 and 7 degrees C. The slow reduction (order of 5-10 min at 7 degrees C) of S2 and S3 with endogenous electron donors other than YD is about twice as fast for S2 as for S3 under these conditions. In contrast, the hydrazine-induced reductive shifts of the formal redox states Si (i = 0...3) are characterized by a totally different kinetic pattern: (a) at 1 mM NH2NH2 and incubation on ice the decay of S2 is estimated to be at least 25 times faster (t1/2 less than or equal to 0.4 min) than the corresponding reaction of S3 (t1/2 approximately 13 min); (b) the NH2NH2-induced decay of S3 is even slower (about twice) than the transformation of S1 into the formal redox state 'S-1' (t1/2 approximately 6 min), which gives rise to the two digit phase shift of the oxygen-yield pattern induced by a flash train in dark adapted thylakoids. (c) the NH2NH2-induced transformation S0----'S-2' [Renger, Messinger and Hanssum (1990) in: Curr.' Res. Photosynth. (Baltscheffsky, M., ed), Vol. 1, pp. 845-848, Kluwer, Dordrecht] is about three times faster (t1/2 approximately 2 min) than the reaction [see text]. Based on these results, the following dependence on the redox state Si of the reactivity towards NH2NH2 is obtained: S3 less than S1 less than S0 much less than S2. The implications of this surprising order of reactivity are discussed. PMID- 2269346 TI - Carbon-13 labelled biotin--a new probe for the study of enzyme catalyzed carboxylation and decarboxylation reactions. AB - [2'-13C]Biotin was incorporated into avidin (egg white), glutaconyl-CoA decarboxylase (EC 4.1.1.70) from Acidaminococcus fermentans and the biotin carrier of transcarboxylase from Propionibacterium freudenreichii (EC 2.1.3.1). 13C-NMR measurements showed an upfield shift of the carbonyl carbon of 3.1 and 2.0 ppm for both enzymes, whereas binding to avidin induced no significant change of the chemical shift as compared to free biotin. The data indicate that the enzymes provide an electronic environment for the covalently bound biotin which favours carboxylation. In addition it was demonstrated by NMR-measurements that glutaconyl-CoA decarboxylase, from which the hydrophobic carboxy-lyase subunit (beta) was removed, could carboxylate free biotin. PMID- 2269345 TI - High-efficiency expression of rat protein kinase C-gamma in baculovirus-infected insect cells. AB - We have expressed rat protein kinase C-gamma in insect cells using a baculovirus vector. The yield of expressed protein kinase C-gamma is about 4% of total protein. The recombinant protein shows a prominent band at about 80 kDa on SDS polyacrylamide gels, which can be identified as protein kinase C-gamma by Western blotting using monoclonal antibodies against protein kinase C-gamma. Upon incubation with [gamma-32P]ATP and in the presence of Ca2+, phosphatidylserine and diacylglycerol this protein autophosphorylates. Its enzyme activity shows the characteristic properties of mammalian protein kinase C. PMID- 2269347 TI - Prediction of prolyl residues in cis-conformation in protein structures on the basis of the amino acid sequence. AB - In proteins most peptide bonds are in trans-conformation: the torsion angle omega = 180 degrees. Only few show cis-conformation in known protein structures (omega = 0 degrees). Most of them are prolyl residues. About 6% of about 4000 prolyl residues are in cis-conformation. Between trans- and cis-prolyl residues significant differences are observed in the surrounding sequences. E.g. there are large amounts of aromatic residues N-terminally in case of cis-prolyl residues, but in the case of trans-prolyl residues more aromatic amino acids occur C terminally. But in all cases there are only complex patterns which are indicative of cis- and trans-conformation, respectively. Considering the neighbours (+/- 6 residues) of prolyl residues and their physicochemical properties we find 6 different patterns which allow one to assign correctly about 75% of known cis structured prolyl residues, whereby no false positive one is predicted. PMID- 2269349 TI - Immunoelectron microscopical localization of the catalytic subunit of cAMP dependent protein kinases in brain microtubules and neurofilaments. AB - The catalytic subunit of cAMP-dependent protein kinases was localized in microtubules and neurofilaments by immunogold electron microscopy. In microtubules, the label was similarly distributed as an immunolabel for the microtubule associated protein MAP 2. The neurofilaments showed no reaction with the MAP 2-antiserum. Our results support the suggestion of an in vivo role of cAMP-dependent protein kinases in the regulation of microtubules. In addition, this is the first demonstration that cAMP-dependent protein kinase is associated with neurofilaments. PMID- 2269348 TI - Formation of tritium-labeled polysialylated gangliosides in the cytosol of rat cerebellar granule cells in culture following administration of [3H]GM1 ganglioside. AB - GM1 ganglioside tritium-labeled at C-3 of sphingosine has been administered to rat cerebellar granule cells. Tritiated polysialylated gangliosides were observed in the cytosol of the cells, where they resulted in a higher amount after a short period of chase. This, together with the data showing an increase of the tritiated polysialylated gangliosides in the total particulate fraction in parallel to the prolonging of the chase period, suggests that cytosolic gangliosides could be a way of transporting neosynthesized gangliosides from the Golgi apparatus to the plasma membranes. PMID- 2269350 TI - Quaternary structure of pigeon liver malic enzyme. AB - Pigeon liver malic enzyme (EC 1.1.1.40) has a double dimer quaternary structure. The NADP+ analogs, aminopyridine adenine dinucleotide phosphate and nicotinamide 1,N6-ethenoadenosine dinucleotide phosphate, bind to the enzyme anti cooperatively. In the presence of non-cooperative competing ligand NADP+, the binding parameter Hill coefficients of these analogues changed very little. Binding of L-malate with enzyme-AADP+ complex first enhanced then reduced the nucleotide fluorescence. Two L-malate binding sites, with Kd values of 23-30 and 270-400 microM, respectively. for the tight and weak binding sites were postulated. A hybrid model between the sequential and pre-existing asymmetrical models was proposed for the pigeon liver malic enzyme. PMID- 2269351 TI - Low density lipoprotein activates monocytes to express tumor necrosis factor. AB - We analyzed the effect of acetylated low density lipoprotein (aLDL) incubation on tumor necrosis factor (TNF) mRNA and protein expression in isolated resting human monocytes in serum free DMEM. TNF mRNA expression was about one third that of PMA and was dose dependent. The maximum stimulatory effect on TNF mRNA was at 250 micrograms/ml, while 500 micrograms/ml induced downregulation. The maximum stimulatory effect occurred at 6 hours, and by 24 hours TNF mRNA expression returned to the resting state. Acetyl LDL also induced the expression of immunoreactive TNF, reaching a sevenfold maximum above control at 12 hours following a 6 hour exposure period. The results suggest that aLDL is a potent stimulator of TNF expression in resting monocytes. This mechanism may be operational in atheroma evolution. PMID- 2269352 TI - The influence of proline residues on alpha-helical structure. AB - Proline lacks an amide proton when found within proteins. This precludes hydrogen bonding between it and hydrogen bond acceptors, and thus often restricts the residue to the first four positions of an alpha-helix. Helices with proline after position four have a pronounced kink [(1988) J. Mol. Biol. 203, 601-619]. In these cases, we find that the proline residue almost almost always occurs on the solvent exposed face of each helix. This positioning facilitates the compensatory hydrogen bonding between solvent and residues P-3 and P-4 (relative to proline, P), through the formation of the kink. Further, it aids in the packing of long helical structures around globular protein structures. PMID- 2269353 TI - Localization of the alpha-oxoacid dehydrogenase multienzyme complexes within the mitochondrion. AB - Bovine kidney mitochondria were separated into matrix and membrane fractions by treatment with digitonin and Lubrol PX. While malate dehydrogenase was found essentially in the matrix fraction, both the pyruvate and the alpha-oxoglutarate dehydrogenase multienzyme complexes remained bound to the inner membrane fraction and became solubilized only after repeated treatments with detergents. Thus both multienzyme complexes must be associated with the inner membrane rather than located within the matrix space. PMID- 2269354 TI - Engineering of microheterogeneity-resistant p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. AB - By site-directed mutagenesis, Cys-116 was converted to Ser-116 in p hydroxybenzoate hydroxylase (EC 1.14.13.2) from Pseudomonas fluorescens. In contrast to wild-type enzyme, the C116S mutant is no longer susceptible to oxidation by hydrogen peroxide and shows no reactivity towards 5,5'-dithiobis(2 nitrobenzoate). Crystals of the C116S mutant are isomorphous with the crystal form of wild-type enzyme. A difference electron density confirms the mutation made. PMID- 2269355 TI - Myosin structure in the eel (Anguilla anguilla L.). Demonstration of three heavy chains in adult lateral muscle. AB - Myosin extracts from central white fibers and peripheral red fibers of the lateral muscle of eel (Anguilla anguilla) were analysed by electrophoresis under non-dissociating conditions, which demonstrated a polymorphism of myosin isoforms. The light and heavy subunit content of the isomyosins was established using SDS-PAGE and two-dimensional electrophoresis. In the central white muscle, 3 myosin isoforms FM3, FM2, FM1, were characterized by 3 types of fast light chain and one fast heavy chain HCf; the existence of a fourth isomyosin is discussed. In the peripheral red muscle, two myosin isoforms were found, SM1 and SM2, each characterized by a specific heavy chain, HCs1 or HCs2, and containing the same slow light chain content. This work demonstrates for the first time the existence of 3 heavy chains in the skeletal muscle of a fish. PMID- 2269356 TI - Ins(1,4,5)P3 formation and fluctuating chloride current response induced by external ATP in Xenopus oocytes injected with embryonic guinea pig brain mRNA. AB - In voltage-clamped Xenopus oocytes injected with embryonic guinea pig mRNA, effective concentrations of extracellular ATP elicited an inward fluctuating current. This current, carried by Cl-ions, was mainly dependent upon liberation of Ca2+ ions from stores as demonstrated by experiments using intracellular EGTA loading and TMB-8 superfusion. Neomycin inhibited these fluctuating currents indicating that the transplanted purinoceptor is linked to phospholipase C activity and triggers Ins(1,4,5)P3 formation. Ins(1,4,5)P3 production evoked by external ATP was clearly demonstrated by directly measuring the water-soluble Ins(1,4,5)P3 level in injected oocytes. Finally, it is suggested that the ATP effect was mediated by a Ca2+ release from Ins(1,4,5)P3 sensitive pools since heparin blocked the ATP responsiveness. The acquired purinoceptor may be made apparent to a P2 subtype since ATP and ADP were equipotent in eliciting Cl- current while AMP and Adenosine were ineffective in injected oocytes. PMID- 2269357 TI - Nuclear factor-1 (NF-1) binds to multiple sites within the transcriptional enhancer of Moloney murine leukemia virus. AB - The transcriptional enhancer of the Moloney Murine Leukemia virus (Mo-MuLV) is comprised of a 75-bp direct repeat, each of which contains multiple binding sites for transcription factors. The occupancy of these sites determines the tissue specificity of expression and disease tropism of the virus. The identification of proteins that bind to this enhancer is therefore required in order to understand the molecular basis of this viral-host interaction. Analysis of the nucleic acid sequence of the Mo-MuLV has identified 4 potential binding sites for the transcription factor NF-1. Evidence is presented using DNAase I protection analysis that NF-1 binds to these 4 sites within the enhancer. The potential role of NF-1 binding in tissue specific expression of Mo-MuLV is discussed. PMID- 2269358 TI - Use of electrospray mass spectrometry to directly observe an acyl enzyme intermediate in beta-lactamase catalysis. AB - Electrospray mass spectrometry was used to directly observe intact acyl enzyme complexes formed between a class C beta-lactamase (from Enterobacter cloacae P99) and four poor substrates/inhibitors. In each case the molecular weight difference between the unreacted and the reacted beta-lactamase was consistent with the formation of an acyl enzyme. PMID- 2269359 TI - Beta-lactoglobulin binds retinol and protoporphyrin IX at two different binding sites. AB - Measurement of tryptophan fluorescence quenching and the excitation energy transfer from tryptophanyl residues to the bound ligand indicates that beta lactoglobulin binds tightly to hemin and protoporphyrin IX in a ligand-to-protein stoichiometric ratio. The apparent dissociation constants of hemin-beta lactoglobulin and protoporphyrin IX-beta-lactoglobulin complexes are 2.5 x 10(-7) M and 4 x 10(-7) M, respectively. The addition of beta-lactoglobulin (final concentration = 10 microM, phosphate buffer 50 mM, pH 7.1) to the solution containing retinol and protoporphyrin IX triggers an energy transfer between beta lactoglobulin tryptophan and protoporphyrin IX as well as between retinol and protoporphyrin IX. The efficiency of energy transfer depends on the distance between the donor (retinol) and the acceptor (protoporphyrin IX). Using the Forster theory, a retinolprotoporphyrin IX distance of 25 A was calculated. These results indicate that retinol and protoporphyrin IX are bound to the beta lactoglobulin monomer at two different sites. PMID- 2269361 TI - Oxidized low-density lipoprotein is chemotactic for arterial smooth muscle cells in culture. AB - The effects of human native and Cu2(+)-oxidized low-density lipoprotein (LDL) were tested on the migration of cultured bovine aortic smooth muscle cells (SMCs) in blind-well chambers. LDL oxidation was controlled by measuring the formation of conjugated dienes and lipid hydroperoxides, and by agarose gel electrophoresis. Oxidized LDL stimulated SMC migration, and the effect was dose dependent up to 200 microgram/ml. The stimulation was chemotactic in nature. Native LDL was without significant activity. The results suggest that oxidized LDL may contribute to the migration of medial SMCs into the intima during atherogenesis. PMID- 2269360 TI - PCR amplification of CGRP II mRNA. Variable expression in tumoral and non-tumoral human thyroid. AB - Two genes code for calcitonin gene-related peptides (CGRPs). One expresses by tissue-specific alternate splicing calcitonin and CGRP I mRNAs, the other CGRP II mRNA. Calcitonin is the marker of sporadic or hereditary human medullary thyroid carcinoma (MTC). CGRP II expression is not well established in normal or tumoral thyroid. After amplification by polymerase chain reaction, CGRP I and II mRNAs were detected in six cases of MTC associated with other endocrine neoplasia (MEN IIa) and in two cases of isolated MTC. CGRP I was detected in all non-C cell tumoral thyroids (6 samples), CGRP II was barely detectable in three out of six cases. CGRP II could be a specific tumoral marker of MTC. PMID- 2269362 TI - Identification of a low-Mr acidic nuclear protein as prothymosin alpha. AB - We have purified to homogeneity a 15-kDa perchloric acid (PCA)-soluble protein from rat thymus nuclei. This highly acidic protein showed a Mr of ca. 30 kDa in acetic acid/urea gels, probably due to oligomer formation. Sequence analysis of internal tryptic and thermolytic peptides revealed that the purified protein is, in fact, prothymosin alpha, a very hydrophilic polypeptide, which has been previously classified as a thymic or immunomodulating hormone. We found that prothymosin alpha is a rather abundant nuclear protein in rat thymus; its concentration is comparable to that of a well-characterized nonhistone protein HMG-14. The subcellular localization and physicochemical properties of prothymosin alpha suggest that its function is related to those of other long polyacidic regions containing nuclear proteins. PMID- 2269363 TI - Two rabbit uricase mRNAs and their tissue-specific expression. AB - Presence of two uricase mRNA species in rabbit was revealed by cDNA cloning. They were different only in the 5'-non-coding region. Their hepatic and extra-hepatic expression in a tissue-specific manner was demonstrated by Northern blot and primer extension analyses. PMID- 2269364 TI - Bacteriorhodopsin in ice. Accelerated proton transfer from the purple membrane surface. AB - The photocycle and the proton pumping kinetics of bacteriorhodopsin, as well as the transfer rate of protons from the membrane surface into the aqueous bulk phase were examined for purple membranes in water and ice. In water, the optical pH indicator pyranine residing in the aqueous bulk phase monitors the H(+) release later than the pH indicator fluorescein covalently linked to the extracellular surface of BR. In the frozen state, however, pyranine responds to the ejected H+ as fast as fluorescein attached to BR, demonstrating that the surface/bulk transfer is in ice no longer rate limiting. The pumped H+ appears at the extracellular surface during the transition of the photocycle intermediate L550 to the intermediate M412. The Arrhenius plot of the M formation rate suggests that the proton is translocated through the protein via an ice-like structure. PMID- 2269365 TI - Multiple polyadenylation sites are active in the alpha 1-tubulin gene from Zea mays. AB - Two cDNA clones (MR2 and MR29) encoding the same alpha-tubulin isotype (alpha 1) have been identified and characterized from maize roots. The sequence of these two cDNA clones is identical to a previously described cDNA clone (MR19) except in the location of their polyadenylation site. The sequence of the cDNA and its homologous genomic clone (MG19/14) shows two putative polyadenylation signals which could direct the variable 3' processing of the observed transcripts. Endonuclease S1 protection analysis in this 3' flanking region confirms the presence in the alpha 1-tubulin gene from Zea mays of these two main functional polyadenylation sites and possibly other related ones. The relative accumulation of RNAs bearing the two main polyadenylation sites has been tested by using a RNA slot analysis of several tissues of the plant. It appears that a higher proportion of shorter mRNA species is found in actively dividing tissues. PMID- 2269366 TI - Autolysis of proproteinase E in bovine procarboxypeptidase A ternary complex gives rise to subunit III. AB - Extracts of bovine pancreatic tissue are shown by HPLC to contain two distinct ternary complexes of procarboxypeptidase A (subunit I), chymotrypsinogen C (subunit II) and either proproteinase E or subunit III. It is shown that proproteinase E in the complex generates subunit III by removal of 13 N-terminal residues when the former is allowed to autolyze in solution or when catalytic amounts of isolated active proteinase E are added to it. Autolysis of proproteinase E was accompanied by the loss of potential activity towards specific synthetic substrates and occurred at a higher rate in pancreatic juice than in pancreatic tissue extracts, even when both were processed in the presence of serine protease inhibitors. We conclude that subunit III (also called truncated protease E) is an autolytic product of proproteinase E and not an ab initio component of the native ternary complex. PMID- 2269367 TI - Interaction of puromycin with acceptor site of human placenta 80 S ribosomes. AB - The complex N-AcPhe-tRNA(Phe).poly(U).80 S ribosome from human placenta was treated with puromycin taken in various concentrations. Based on the kinetic data of N-acetylphenylalanyl-puromycin formation, the association constant of puromycin with the acceptor site of the ribosome was estimated to be (3.96 +/- 0.84) x 10(4) M-1 at 37 degrees C. PMID- 2269368 TI - A rapid burst preceding the steady-state rate of H(+)-transhydrogenase during illumination of chromatophores of Rhodobacter capsulatus. Implications for the mechanism of interaction between protonmotive force and enzyme. AB - At the onset of illumination of chromatophores there was a burst (t1/2 approx. 5 ms) in the rate of the H(+)-transhydrogenase reaction before establishment of the steady-state rate. The burst was suppressed at high pH with a pKa of approx. 8.5. The burst and the steady-state rate were inhibited by either (i) a combination of myxothiazol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, or (ii) NAD+, or (iii) dicyclohexylcarbodiimide. The results support a model in which substrate binding to H(+)-transhydrogenase is relatively fast. A subsequent slow step is accelerated by the protonmotive force and a third step, possibly product release, is rate-limiting in steady-state turnover during illumination. PMID- 2269369 TI - Association of brain spectrin isoforms with microtubules. AB - The relationship of rat brain spectrin isoforms to microtubules of newborn and adult animals was studied. Spectrins were minor components in microtubule preparations. The microtubule-associated spectrin is a major calmodulin-binding protein. Radiolabelled brain spectrin(240/235) revealed specific microtubule binding activity in vitro, possibly via a tubulin. PMID- 2269370 TI - Sequence analysis of the potent mitogenic toxin of Pasteurella multocida. AB - Pasteurella multocida toxin is a potent mitogen for cultured Swiss 3T3 cells where it causes an accumulation of inositol phosphates and activation of protein kinase C. The gene sequence described here coded for a 146 kDa protein. The ORF was preceded by a ribosome binding site and followed by a stem loop. There was no evidence for a signal sequence. The gene had a low G + C base ratio which differs from the rest of the Pasteurella genome. There was no significant homology with other known proteins, although a motif found in certain bacterial toxins which are ADP-ribosyl transferases is present. A recombinant expressing only part of the PMT gene was not mitogenic. PMID- 2269371 TI - Inhibition of phosphatidic acid phosphohydrolase activity by sphingosine. Dual action of sphingosine in diacylglycerol signal termination. AB - Recent evidence indicates that a major fraction of diacylglycerol that is produced in hormonally stimulated cells arises by phosphatidylcholine hydrolysis via the sequential action of phospholipase D and phosphatidic acid phosphohydrolase (PAP). We have previously reported that sphingoid bases stimulate phospholipase D activity in NG108-15 cells. The evidence presented here demonstrates that in sphingosine-treated NG108-15 cells, elevated phosphatidic acid levels are accompanied by a parallel, time- and dose-dependent decrease in diacylglycerol levels. DL-propranolol, a known inhibitor of PAP, exerted similar effects, suggesting that the action of sphingosine may have been due to inhibition of PAP activity. This prediction was confirmed in in vitro experiments in which it was demonstrated that sphingosine is as potent an inhibitor of both cytosolic and membrane-associated PAP activity as propranolol. The hypothesis that sphingoid bases may exert a dual action in diacylglycerol signal termination is proposed. PMID- 2269372 TI - Mapping of the region of the tick-borne encephalitis virus replicase adjacent to initiating substrate binding center. AB - Affinity labelling with aldehyde-containing analogs of initiation substrates of nuclear fraction of tick-borne encephalitis virus (TBEV) infected cells results in a labelling of a single polypeptide with a molecular mass of 68 kDa which was immunologically identified as TBEV NS3 protein. A single-hit hydroxylamine hydrolysis, using limited and long-term CNBr cleavages allowed one to identify Lys1800 and/or Lys1803 as the label attachment sites. These amino acid residues are situated in the proximity of the 'B'-site of NTP-binding motif of viral RNA replicase. PMID- 2269373 TI - Structure and expression of rat muscle-specific enolase gene. AB - The structure of rat muscle-specific enolase (beta beta enolase) gene was determined. It comprises 12 exons of various lengths (59-223 bp) spanning about 6 kbp and its exon-intron organization is similar to that of neuron-specific enolase (gamma gamma enolase) gene. A transcriptional start site was identified by a combination of S1 nuclease mapping and primer extension analyses. In the 5' flanking region we found a TATA-box-like sequence and several MyoD-binding motifs. The in vitro cell free transcription of the truncated genomic DNA fragment using HeLa cell extract showed that the transcription start site has been correctly identified and the promoter sequences work well. PMID- 2269374 TI - On pigmented macules and butterfly collection. PMID- 2269375 TI - Laugier's disease. AB - Pigmented macules of the malpighian mucous membranes have been described under numerous names since the first description by P. Laugier in 1970 of the 'pigmentation melanique lenticulaire essentielle de la muqueuse jugale et des levres'. In this paper, we show that (1) the lesions may occur in all malpighian mucous membranes, (2) are easily distinguished from melanoma both clinically and if necessary by histology, and we suggest (3) that, whichever the localization is, the condition should be called Laugier's disease. PMID- 2269376 TI - Mineralization of collagen and elastic fibers in superficial dystrophic cutaneous calcification: an ultrastructural study. AB - The ultrastructural morphology of localized skin calcifications without associated diseases and with normal serum calcium and phosphate ion values is still unknown. In a case of superficial dystrophic calcinosis cutis (DCC), the role of collagen, elastin and ground substance in the process of calcification and the organization of the apatite crystals could be studied by light and electron microscopy despite technical difficulties in sectioning the hard tissue. Ultrastructural investigation revealed the nucleation of calcification being related to collagen and elastic fibers. No intracellular calcification was found. A flower-like arrangement of pleomorphic crystals was found around single collagen fibrils resembling the calcification of collagen seen in bone tissue. The elastic fibers showed a different pattern of calcification compared with other diseases (e.g. pseudoxanthoma elasticum) with known calcification of the elastic fibers. The process of mineralization was initially linked to the microfibrils of the elastic fiber. PMID- 2269377 TI - T cell receptor gene rearrangement analysis in mycosis fungoides and disseminated lymphocytoma cutis. AB - A cDNA from the CT beta 2 region of the T cell receptor gene was used as a probe to investigate the clonal composition of T cells in the skin lesions of 3 patients with mycosis fungoides (MF) and 1 patient with disseminated lymphocytoma cutis (DLC). All of these skin lesions showed helper/inducer T cell dominant infiltration. Clonal T cell populations, as evidenced by rearranged DNA bands, were demonstrated in all the skin lesions of the 3 patients with MF, but not in the lesion of the patient with DLC. The patients with MF appeared to have the same gene rearrangement pattern in DNA obtained from separate lesions, providing evidence that the T cells in both sites were derived from the same clone. Our results show that this gene rearrangement analysis helps to diagnose difficult cases of lymphoproliferative disorders. PMID- 2269378 TI - In vivo evaluation of unbound water accumulation in stratum corneum. The influence of acute skin irritation induced by sodium laurylsulfate. AB - In a series of previous experiments, we showed that the inflammatory response associated with skin barrier function damage induced by sodium laurylsulfate (SLS) was correlated with the concentration of SLS and with the duration of application under occlusion of the surfactant. In this experiment, we measured accumulation of unbound water that occurred when occlusive contact was maintained during a short period of time between the skin and the probe head of an electrometric device. Accumulation of unbound water was expressed as area under the curve (sum of increments of skin capacitance during a 45-second period of time; AUCC). For comparative purposes, we also measured transepidermal water loss (TEWL). Both skin function parameters were established for each individual skin site before and 24 h after removal of SLS patches (10, 5, 1 and 0% control solution under occlusion for 48 h). After SLS insult, AUCC and TEWL were increased, and changes were related to SLS concentration (p less than 0.0002). There was a linear correlation between AUCC and log TEWL (p less than 0.0002). On normal skin before application of SLS both parameters were also correlated (p less than 0.04). The regression line between AUCC and log TEWL of normal skin differed however from that observed on SLS-pretreated sites. This indicates that electrometric data are able to simultaneously characterize changes in skin hydration, a rather static parameter, and changes in the amount of unbound water accumulation (AUCC), a dynamic parameter which proved to reflect TEWL. PMID- 2269379 TI - Decreased natural killer cell function in patients with classical Kaposi's sarcoma. AB - Natural killer (NK) cell activity of peripheral blood lymphocytes was evaluated in a group of 13 patients with classical Kaposi's sarcoma (KS). All patients had a normal T4/T8 ratio, and the disease was confined to the skin of the lower extremities. A group of 5 healthy subjects served as controls. NK cell function was significantly decreased in patients as compared to controls. Our result is similar to that found in another group of patients with AIDS-related KS with lymphadenopathy and an abnormal T4/T8 ratio. This suggests that decreased NK cell function is not a result of a progressive process and might be directly involved in the development of KS. PMID- 2269380 TI - Combination of topical calcipotriol (MC 903) and UVB radiation for psoriasis vulgaris. AB - The synthetic compound MC 903 (calcipotriol) is a structural analogue of the naturally occurring, biologically active 1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3]. MC 903 and 1,25-(OH)2-D3 show similar receptor binding and comparable effects on cell differentiation. However, MC 903 appears to be at least 100 times less potent in its effects on calcium metabolism. In previous double-blind placebo-controlled studies, topical MC 903 has been shown to have a therapeutic effect in psoriasis. The present open study involving 20 patients with psoriasis vulgaris was a right/left comparison of the efficacy and tolerability of MC 903 ointment (50 micrograms/g) alone or with UVB radiation. After treatment for 8 weeks, topical MC 903 alone resulted in marked improvement in 66% of the patients and in clearance in 17%. Combination of topical MC 903 with UVB resulted in marked improvement in 50% of the patients and in clearance in 39%. These differences were not statistically significant. No significant change in serum calcium levels was detected. Two patients developed a facial dermatitis which disappeared spontaneously during continued treatment. These results show that the combination of topical MC 903 and UVB radiation is well tolerated. Larger-scale studies are warranted to answer the question whether UVB radiation induces a significant improvement of the antipsoriatic effect of topical MC 903. PMID- 2269381 TI - Cyclosporin in localized and systemic scleroderma--a clinical study. AB - Four patients with systemic scleroderma and 1 patient with localized scleroderma were treated with ciclosporin (CS), given in daily doses between 2.2 and 5.6 mg/kg body weight for 3-26 months. Under this medication clinical improvement was observed in 4 patients with partial regression of cutaneous sclerosis and inflammation, healing of fingertip ulcerations or leg ulcers and improvement of articular mobility. However, in 1 patient with rapidly advancing systemic scleroderma a short-term therapy with CS in low doses (2-3 mg/kg body weight) resulted in arterial hypertension and renal dysfunction. Therefore careful selection of patients and close-meshed controls are indicated when CS is considered as anti-inflammatory treatment in scleroderma. PMID- 2269382 TI - Linear sebaceous nevus syndrome. AB - A boy with linear sebaceous nevus syndrome was followed up to 3 years of age, at which time he died of pneumonia. The lesions of nevus sebaceus were located in the midline and on both sides of the face, and there were partial colobomata of the right outer canthus continuous with pseudopterygium and of the left upper eyelid. At 2 months of age, the patient developed infantile spasms. At 1 year, electroencephalography revealed hypsarrhythmia, and left carotid angiography showed an arteriovenous malformation. At 2 years, the mental retardation and delayed motor development were detected. PMID- 2269383 TI - Extremely extended Fournier's gangrene. AB - We describe a 19-year-old Japanese man with severe extensive necrotizing fasciitis that started as Fournier's gangrene to involve the external genitalia, thigh and lower abdomen. High creatine phosphokinase, transient immunosuppression (reduced serum IgG level and negative tuberculin skin test reaction) and disseminated intravascular coagulation occurred during the necrotizing fasciitis. PMID- 2269384 TI - Esophageal involvement in pemphigus vulgaris: report of two cases and review of the literature. AB - Two patients with esophageal involvement of pemphigus vulgaris are presented, who were diagnosed histopathologically and by direct immunofluorescence. In most dermatological textbooks the possibility of esophageal involvement is not mentioned. In the English medical literature 11 cases have been reported. It seems that if upper gastrointestinal endoscopy had been done on a routine basis it might have shown that esophageal involvement is more widespread than present findings indicate. PMID- 2269385 TI - Management of nonstaphylococcal toxic epidermal necrolysis. PMID- 2269386 TI - Chronic vulvar purpura. PMID- 2269387 TI - Danazol and discoid lupus erythematosus. PMID- 2269388 TI - Tufted angioma. AB - The clinical and histological description of 2 cases of tufted angioma is presented. PMID- 2269389 TI - Disseminated superficial actinic porokeratosis. A differential diagnosis for lichen planus atrophicus. PMID- 2269390 TI - Squamous cell carcinoma and basal cell carcinoma within the clinical picture of a chronic venous insufficiency in the third stage. AB - Two cases of neoplastic ulcers of the leg will be described which presented themselves within the clinical picture of a chronic venous insufficiency in its third stage. Both cases had a phlebological anamnesis. The transformation of chronic ulcers of the leg into spinal cell carcinomas is well known. With the presence of an ulcus cruris, however, basal cell carcinomas are rarely considered in a differentiated diagnosis. Yet both of these (by and large common) skin tumors can occur in the clinical picture of an ulcus cruris. The role of the dermatologist in the early diagnosis and treatment such neoplastic ulcers is therefore an important one. PMID- 2269391 TI - Successful immunotherapy by dinitrochlorobenzene in a case of recurrent acrolentiginous melanoma. PMID- 2269392 TI - Kaposiform acro-angiodermatitis with arteriovenous malformation (Stewart-Bluefarb syndrome). AB - A case of acro-angiodermatitis with congenital arteriovenous fistulae (Stewart Bluefarb syndrome) at the distal right foot in a young man is reported. The lesion evolved slowly from a small dark-red spot existing from birth. Besides mechanical disturbances, the patient's only symptoms were a warmer and somewhat bigger right foot compared to the left nonaffected side. He presented a circumscribed spongy, livid-red coloured angiomatous lesion at the upper part of the distal right foot, also involving the proximal parts of the three middle toes. The diagnosis was based on the clinical aspect and the findings by Doppler ultrasonographic and oscillographic examination. The transcutaneous oxygen pressure showed a marked hypoxia at the edge of the acro-angiodermatitis. Finally, arteriovenous fistulae were demonstrated by arteriography. PMID- 2269394 TI - Regulation of insulin-like growth factor-I messenger ribonucleic acid expression in Leydig cells. AB - In the present study, we evaluated insulin-like growth factor-I (IGF-I) messenger RNA expression in the rat testis. Crude interstitial cells were separated into three distinct bands on 15-60% Percoll density gradients. IGF-I mRNA was mainly localized in the Leydig cell-enriched fraction (band 3), while band 1 and band 2 cells did not contain significant amounts of IGF-I mRNA. Leydig cell IGF-I mRNA consisted of multiple species varying from 0.8 to 7.5 kb and was present in rat Leydig cells all ages examined, from 25 to 55 days old. To further document that IGF-I mRNAs are present in Leydig cells, the method of Klinefelter et al. (Biol. Reprod. (1987) 36, 769-783) was used to isolate highly purified (greater than 98% pure) Leydig cells. Most of the IGF-I mRNA was localized in these Leydig cells, while there was no detectable IGF-I mRNA in the whole testis or other interstitial cells. Furthermore, IGF-I mRNA in Leydig cells was increased more than 2-fold by growth hormone (GH) administration in vivo. This suggests that IGF I mRNA in Leydig cells is also GH dependent. Interstitial IGF-I produced in Leydig cells may have both autocrine and paracrine effects in the testis. PMID- 2269393 TI - The mRNA of protein disulfide isomerase and its homologue the thyroid hormone binding protein is strongly expressed in adipose tissue. AB - The thyroid hormone 3,3',5-triiodothyronine (T3) plays an important role in the differentiation of adipocytes, as well as in the thermogenic activity of brown adipose tissue. Recently a T3 binding protein (T3BP), which is associated with plasma membranes, has been isolated and cloned from liver. It proved to be homologous to the multifunctional enzyme protein disulfide isomerase (PDI), which is involved in posttranslational modifications of secretory proteins. In this study we investigated the T3BP/PDI mRNA expression in white and brown adipose tissue of rat and bovine, as well as in several rodent adipose cell lines at various states of differentiation. T3BP/PDI mRNA expression was found in white and brown adipose tissue, as well as in preadipocytes and adipocytes at all states of differentiation. Comparison to other tissues (liver, kidney, heart, brain) revealed that its expression was highest in white fat. No modulation of T3BP/PDI mRNA corresponding to different adaptational or developmental situations could be detected in adipose tissue. PMID- 2269395 TI - Opposite effects of estrogen and the progestin R5020 on cell proliferation and GCDFP-15 expression in ZR-75-1 human breast cancer cells. AB - We have recently demonstrated that physiological concentrations of androgens caused a marked inhibition of basal and 17 beta-estradiol (E2)-induced cell growth in ZR-75-1 human breast cancer cells. Moreover, these steroids exert effects on GCDFP-15 (gross cystic disease fluid protein-15) expression that are opposite to their above-indicated actions on cell proliferation. The synthetic progestin R5020 (17.21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), on the other hand, causes a potent inhibition of E2-induced ZR-75-1 cell growth. In order to further characterize the hormonal regulation of GCDFP-15 expression and to better understand the antagonism between progestin and estrogen action in breast cancer cells, we have studied the effect of R5020 on both GCDFP-15 expression and cell growth in ZR-75-1 cells. After a 10-day incubation, the 4-fold stimulatory effect of 1 nM E2 on cell growth was 60% decreased by maximal effective concentrations of R5020 (greater than 1 nM) while, in the absence of E2, R5020 had no effect. The mitogenic action of E2 was accompanied by a 75% inhibition of GCDFP-15 secretion while nanomolar concentrations of R5020 induced 1.4- and 5.2-fold increases in GCDFP-15 secretion in control and E2-treated ZR-75-1 cells, respectively. While E2 caused a marked inhibition of GCDFP-15 mRNA levels, R5020 induced a maximal 2- to 3-fold increase (above control) in GCDFP-15 mRNA accumulation in cells simultaneously incubated with E2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269397 TI - Angelman's syndrome in the first year of life. AB - Angelman syndrome usually has been considered to be rare and sporadic. However, recent reports suggest a sibling recurrence risk of just under 25 per cent, so early diagnosis is very important. The authors report Angelman syndrome in a child of seven months. The early features of this syndrome (jerky movements, EEG characteristics, chromosomal abnormalities in half the cases) should make it possible to diagnose or suspect the syndrome in the first year of life. PMID- 2269396 TI - Production of rat renin fusion protein in Escherichia coli and the preparation of renin-specific antisera. AB - Rat renin fused at the N-terminus with Sj26, a 26,000 Da glutathione S transferase of Schistosoma japonicum, was expressed in Escherichia coli. The fusion protein was soluble and easily purified from crude bacterial lysates by affinity chromatography on immobilised glutathione. The fusion protein possessed no detectable renin activity. Antisera raised in rabbits against the fusion protein were specific for renin. These antisera did not bind soluble renin but bound immobilized renin. By immunoblotting, these antisera demonstrated rat renin to migrate on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two broad bands of 33,000-34,000 and 35,000-37,000 Da. By immunocytochemistry of rat tissues, these antisera stained renin containing cells in the afferent arteriole of the glomerulus of the kidney, the zona glomerulosa of the adrenal and the corpus luteum of the ovary. However, apart from the afferent arteriole of the kidney, no immunoreactive renin was identified in blood vessels of the kidney, adrenal or ovary. These studies demonstrate that a recombinant renin fusion protein is a valuable alternative approach for the preparation of renin-specific antisera. PMID- 2269398 TI - Are boys more vulnerable to psychosocial growth retardation? PMID- 2269399 TI - Seizures in patients with cerebral palsy. PMID- 2269400 TI - Dexamethasone therapy. PMID- 2269401 TI - Neurological test for at-risk children. PMID- 2269402 TI - Getting the word about. PMID- 2269403 TI - Born too small--is outcome still affected? AB - A cohort of boys weighing below the 2nd centile at birth between 1973 and 1974 were assessed at 10 to 11 years of age. Control children from the same population were matched for social class and age. Two boys in the light-for-dates group were profoundly disabled and were excluded from assessment. After these exclusions, there were no differences in intelligence or school achievement between the two groups, although tests of temperament and behaviour suggested some correlation between features of the 'attention deficit disorder' and the extent to which birthweight deviated from normal. Matching for social class is likely to have eliminated the confusing environmental and family influences associated with the poor outcome reported in a previous study of light-for-dates boys. In addition, improved perinatal care is likely to have contributed to the protection from long term sequelae of the light-for-dates infants in the present study. PMID- 2269404 TI - Psychiatric disorders at five years among children with birthweights less than 1000g: a regional perspective. AB - The relationship between extremely low birthweight (ELBW) and psychiatric disorder was investigated in a cohort of children of 500 to 1000g birthweight, born between 1980 and 1982. At five years of age data were collected for 82 of 90 survivors on psychiatric symptoms, parent-reported developmental delay and various aspects of psychosocial disadvantage. Compared with controls, ELBW children did not come from more disadvantaged environments, but were much more likely to experience developmental delay and problems with motor co-ordination. 16 per cent had an attention deficit disorder with hyperactivity (ADDH), compared with 6.9 per cent of controls. Rates of conduct disorder and emotional disorder were not raised, indicating that ELBW is a specific risk factor for ADDH. Controlling for the effect of neurodevelopmental problems rendered the association between ELBW and ADDH non-significant. PMID- 2269405 TI - The incidence and natural history of scoliosis in Rett syndrome. AB - A survey on spinal deformity was conducted by means of a questionnaire mailed to the 350 American families who are members of the International Rett Syndrome Association. 258 questionnaires were completed and further information (medical records and radiographs) was received from treating physicians. Scoliosis was present in 119 patients, whose clinical details are discussed. Patients with Rett syndrome frequently develop progressive scoliotic deformities. The incidence increases with age, occurring most commonly during the second decade. Bracing to control curve progression has been largely unsuccessful for adolescent patients. PMID- 2269406 TI - Cultural differences in family communication about Duchenne muscular dystrophy. AB - This study compared the patterns of communication and use of professional support systems of Irish and American families with sons with Duchenne muscular dystrophy (DMD). Structured interviews were used with the parents of 34 Irish boys and 21 American boys attending the muscular dystrophy services of Central Remedial Clinic, Dublin, and Children's Hospital, Boston. A matched control group was interviewed in each culture to compare use of professional support systems. Difficulties in communicating about DMD with their spouses and with their affected sons were reported by significantly more Irish parents than by their American counterparts. More Irish parents had never spoken about DMD with their affected sons. American DMD families reported significantly more contact with professional support systems than did the Irish families. Factors which may contribute to these cultural differences are discussed. PMID- 2269407 TI - Deficits in reciprocal inhibition of children with cerebral palsy as revealed by H reflex testing. AB - Experiments were performed to determine whether spinal and supraspinal components of reciprocal inhibition (a neural mechanism responsible for the prevention of muscular co-ordination during voluntary movement) were present in groups of non disabled children and children with cerebral palsy. Changes in the gastrocnemius soleus H reflex were examined during voluntary dorsiflexion and plantarflexion of the ankle and during a vibration applied to the anterior tibial tendon. The results indicate that children with cerebral palsy have impairments in reciprocal inhibition, both before and during voluntary movement. These deficits, which involve damage to supraspinal centres, contribute to their inability to perform smooth, co-ordinated movements. PMID- 2269408 TI - Use of benzhexol hydrochloride to control drooling of children with cerebral palsy. AB - The use of benzhexol hydrochloride to control drooling was evaluated in a group of 20 children with cerebral palsy. Drooling was measured before treatment and then repeatedly until an optimal dosage of benzhexol hydrochloride was attained. 17 of the 20 children showed an improvement in drooling, and side-effects were minimal. This type of medication appears to be useful in the treatment of drooling. PMID- 2269409 TI - Power spectral analysis of the EEG of term infants following birth asphyxia. AB - The aim of this pilot study was to perform power spectral analysis of the EEGs of term infants following birth asphyxia, to establish its value as a prognostic indicator. 16 term infants were studied over an 18-month period. Power spectral analysis was performed on the EEGs of babies with signs of hypoxic-ischaemic encephalopathy at regular intervals during the first five days of life. It showed distinct changes following birth asphyxia, which were related to the eventual outcome of the babies. Absolute power was significantly reduced in the babies with poor outcome compared with those with good outcome, particularly in the delta bands. PMID- 2269410 TI - Effects of congenital HIV infection on neurodevelopmental status of babies in foster care. AB - High rates of neurological complications related to congenital HIV infection have been reported, but often it has been difficult to delineate those clinical impairments specifically related to viral infection of the developing nervous system. The present study attempted to hold causative environmental factors constant by comparing the neurodevelopmental and growth status of two matched control groups of infants in foster care, one HIV seronegative and one seropositive. All were over the age of 15 months and had been born to seropositive mothers. The seropositive group showed significantly more neurological involvement than the seronegative group, and a different pattern of cognitive deficits. There were no significant differences in growth measures between the two groups. Babies born to HIV seropositive mothers were generally at high risk for developmental impairments. PMID- 2269411 TI - Self-assessment and impairment in adult/elderly hearing screening--recent data and new perspectives. AB - Because self-assessment measures are helpful in identifying handicap/communication difficulties, they have an important place in hearing screening protocols for adult/elderly persons. When impairment is used as the criterion, questionnaire results can be used to calculate sensitivity, specificity, predictive values, and efficiency for a variety of fences. Findings are summarized for 2825 persons on three different questionnaires that reveal adequate, reasonably similar, and predictable relationships between impairment and self-assessment findings. However, evidence on "deny-ers" (persons with impairment who deny their handicap) and "complainers" (persons who complain about handicap but have no impairment) are also presented. These latter findings show a strong rationale for using self-assessment measures in their own right, and not simply as an alternate, less effective method for measuring pure-tone impairment. PMID- 2269412 TI - "The measurement of hearing handicap" revisited: a 20-year perspective. AB - Interest in the development of self-assessment instruments to measure the handicapping effect of hearing difficulty has grown in the last 20 years. Numerous paper and pencil instruments are now available which vary in purpose, design, and psychometric underpinings. This paper discusses the status of the self-assessment approach in clinical audiology, presents a point of view regarding some of the factors contributing to this status and proposes some frontiers still open to self-assessment instruments in the assessment of hearing handicap. PMID- 2269413 TI - Hearing screening in a dental office using self-assessment. AB - Experiences in a statewide health fair screening program prompted development of alternate methods for screening hearing of adults including one in a dental office summarized here. Because it was considered impractical to use pure-tone screening, several self-assessment procedures were tested against pure-tone findings in a pilot study. As a result, the Rating Scale for Each Ear (RSEE) was selected for use. In the pilot and main study, 796 adult dental patients were evaluated and 21 to 29% failed the screening, depending on whether self assessment procedures or pure tones were used. Although the dental office staff was generally supportive of the program, there were some problems in implementation. The number who returned for follow-up (N = 14) was disappointing, but there were several very positive benefits to the program including distribution of earplugs and education on the adverse effects of noise. In terms of general feasibility of such screening, from an epidemiology standpoint the program was judged to have good efficacy and efficiency but there were serious problems in effectiveness. PMID- 2269414 TI - Self-assessed satisfaction levels in elderly hearing aid, eyeglass, and denture wearers. A cross-modality comparison. AB - Self-assessed satisfaction ratings with a seven-point scale were used to evaluate user success with recent technology (canal type) hearing aids in an elderly population. To evaluate possible age-related influences on satisfaction judgments, data were also gathered from separate groups of eyeglass and denture wearers from the same population. Highest satisfaction responses were reported by denture wearers, whereas the lowest satisfaction judgments were reported by hearing aid wearers. Among hearing aid subjects, satisfaction was inversely related to age. Compared with published hearing aid satisfaction data, study findings supported the conclusion that canal type hearing aids are neither superior or inferior to other styles of hearing instruments with this age group, in so far as user satisfaction is concerned. PMID- 2269415 TI - Case study examples using self-assessment. AB - The following case studies demonstrate the application of self-assessment techniques. The selection of procedures reported here is not meant to imply necessarily that these procedures are more or less effective or more widely used than other available self-assessment tests, but rather to illustrate the various purposes for which self-assessment tools may be employed. Case 1 illustrates the contribution of data obtained from the Hearing Performance Inventory (Giolas, Owens, Lamb, & Shubert, 1979) in the management and counseling of a severely hearing impaired adult. Case 2 involves the use of the Hearing Problem Inventory developed by Hutton in Atlanta (HPI-A, Hutton, 1987). Application of the Self Assessment of Communication (SAC) and Significant Other Assessment of Communication (SOAC) (Schow and Nerbonne, 1982) is shown in Case 3, whereas Case 4 demonstrates the usefulness of the Hearing Handicap Inventory for the Elderly (HHIE, Ventry and Weinstein, 1982). Both the SAC/SOAC and HHIE batteries involve problem cases associated with hearing aid fitting and assessment of benefit. The final illustration (Case 5) is a report on the Children's Auditory Processing Performance Scale (CHAPPS), a new questionnaire developed by Smoski, Brunt, and Tannahill/ISHA (1987) for assessing parent's judgment of children's listening abilities (Appendix). The versatility of self-assessment applications across a broad assortment of impairment levels, age groups, and clinical settings is demonstrated in these cases. Hopefully the reader will see more clearly the application and value of these and other non-audiometric techniques and will be motivated to increase the use of self-assessment tools in the individual work setting. PMID- 2269416 TI - Fundamental issues in self-assessment of hearing. AB - The history of self-assessment for hearing is reviewed from its beginning use in the 1930s to its emerging importance in the 1980s. It is presented as a more systematic method for interviewing the patient, and although it does not always agree with pure-tone findings, it should be recognized as a useful assessment method to be used in combination with other measures of hearing. The uses for self-assessment, psychometric concerns, issues in the definition of hearing domains (disorder, impairment, handicap, disability), and new frontiers also are discussed in this overview article. PMID- 2269417 TI - Ryanodine receptor purified from crayfish skeletal muscle. AB - The ryanodine receptor was isolated from the sarcoplasmic reticulum of crayfish skeletal muscle. Ryanodine binding to the native fraction was measured by Scatchard analysis and values of 60 nmol/l and 9 pmol/mg were obtained for KD and Bmax respectively. The identity of purified receptor was confirmed by electron microscopy, electrophoresis and incorporation into planar lipid bilayers. At least two conductance states (100 pS and 50 pS) were observed in 100 mmol/l NaCl both for native and purified receptor. PMID- 2269419 TI - Mutual interactions of the phosphate groups in locally deformed backbones of various DNA double helices at high salt concentrations. AB - Changes in the free energy of mutual phosphate group interactions are calculated that accompany bending of the A-, B- and Z-DNA backbones in 0.7, 2.1 and 4.2 mol/l NaCl aqueous solutions. The bending is often found to be favoured in the direction of the double helix grooves; B-DNA prefers bending into the major groove while minor groove is the preferred bending direction of A-DNA in the presence of 0.7 mol/l NaCl. Interestingly, the preferences are reversed in 4.2 mol/l NaCl. Further stabilization of A-DNA and B-DNA backbones is achieved in some cases if bending is combined with suitable local double helix twist alterations. Bending tendencies of Z-DNA backbone are generally weaker and they decrease, in contrast to B-DNA and A-DNA, with the increasing ionic strength. PMID- 2269418 TI - Non-junctional modulation of neurogenic twitches of the guinea-pig ileum by some peptides and other compounds in the triple bath. AB - The effects of some neuropeptide transmitter candidates and of some other neurotoxins or drugs on conduction of neural excitation were studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment so that the aboral segment might also be invaded. Drugs were added to the middle segment to affect neuronal propagation (non-junctional effects) which was monitored by twitch amplitude of the aboral segment. The application of bradykinin and cromakalim did not affect aboral twitches although strong contractile and relaxatory effects were observed when the drugs were applied directly to the aboral segment; no neurogenic effects thus manifested. Capsaicin and neurotensin, when applied both to the middle and aboral segments, elevated the tone of the preparations accompanied with a decrease in twitch amplitude; these effects may have been due to neurogenic stimulation and release of other motor neurotransmitters. The application of VIP, apamin and dendrotoxin to the middle as well as to the aboral segments augmented aboral twitches, which might be at least partly due to facilitation of nerve action potential propagation in nerve terminals of cholinergic motor fibres. PMID- 2269420 TI - Na(+)-Ca2+ exchange in locust striated muscles. AB - High Na+ + Ca2+ exchange rates comparable with those reported for crayfish striated muscle, rat heart and rat brain, were observed in locust striated muscle homogenates and membrane preparations. The Na(+)-Ca2+ exchange followed the 1st order kinetics with a Km value of 18 mumol.l-1 for Ca, the pH optimum was at 8, the temperature optimum at 30 degrees C, and the exchange was inhibited in the presence of sodium in the incubation medium, with a KiNa of approx. 25 mmol.l-1. The present results suggest a high Na(+)-Ca2+ exchange in locust striated muscles which operate on the calcium electrogenesis principle. PMID- 2269421 TI - Hybridization frequencies of different mammalian cell types by electrofusion. AB - The efficiency of electrofusion of four types of cells: CHO, HeLa, mouse melanoma cells and human skin fibroblasts has been studied. The frequencies of fusion products were determined 1) directly in a closed flow-through fusion chamber after dielectrophoresis and pulsation; 2) after short-term postfusion cultivation period of 5 to 10 minutes; and 3) in various intervals up to 30 hours after fusion induction. No substantial differences were found in the rates of formation of heterokaryons and synkaryons between the individual cell types, and this confirmed the uniformity of the effects of electric fields on diverse cell membranes. After 5 hours of culture the yield of fusion products reached 15 to 35% in various cell combinations and the frequencies of synkaryons reached up to 7% in almost all the combinations studied 24 to 30 hours after fusion. PMID- 2269422 TI - Hydroxylamine as an inhibitor and terminal acceptor in the respiratory chain of the bacterium Paracoccus denitrificans. AB - Three sites of inhibitory action of hydroxylamine were identified in the respiratory chain of anaerobically grown bacterium Paracoccus denitrificans. Terminal oxidases were blocked at concentrations of 10(-4) to 10(-3) mol.l-1, and the inhibitor competed with artificial donor of electrons N, N, N', N' tetramethyl-l, 4-phenylenediamine. In the anaerobic part of the respiratory chain inhibition of nitrite reductase and apparently also nitric oxide reductase occurred, resulting in the increased accumulation of nitric oxide during denitrification. These effects together with the inhibition of terminal oxidases by nitric oxide are probably realized through switching the electron flow from oxygen to nitrogen terminal acceptors in the presence of hydroxylamine. By means of difference spectroscopy, the respiratory inhibitor mucidin and a cytochrome c deficient mutant of Paracoccus denitrificans, hydroxylamine could be shown to serve also as a terminal acceptor of the cytochrome c region. Reduction of hydroxylamine to ammonia was at the same time accompanied by the formation of transmembrane electrical gradient. Hydroxylamine reductase was purified 123-fold from the periplasmatic cell fraction by FPLC; the product obtained showed the features of respiratory nitrite reductase of the cytochrome cd1 type. PMID- 2269423 TI - Adsorption of bovine muscle lactate dehydrogenase to erythrocyte membranes. PMID- 2269424 TI - Concentration dependent active transport, osmotically active nonpermeable component and bioreactor volume regulation. PMID- 2269425 TI - New light on Myc and Myb. Part I. Myc. PMID- 2269426 TI - The HIV-1 long terminal repeat contains an unusual element that induces the synthesis of short RNAs from various mRNA and snRNA promoters. AB - We describe an unusual element that activates the synthesis of short transcripts from a wide variety of mRNA and small nuclear RNA (snRNA) promoters, including the U6 RNA polymerase III promoter. This inducer of short transcripts (IST) is located between positions -5 and +82 relative to the cap site in the HIV-1 LTR. In the presence of IST, the total transcriptional activity of the different promoters is greatly increased, but the resulting additional RNA molecules are short, ending around position +60. IST is not the RNA target (TAR) for Tat trans activation; however, because it relies entirely on cellular factors for activity, IST may serve to provide abundant RNA targets for Tat trans-activation without a requirement for full-length viral mRNA expression. PMID- 2269427 TI - An in vitro globin gene switching model based on differentiated embryonic stem cells. AB - We used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro. We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation, a switch occurs to the fetal/adult genes. In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies. We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development. When the human epsilon- or beta-globin genes driven by the dominant control region (DCR) are introduced into this system, the human epsilon-globin gene, in contrast to the beta-globin gene, is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene. We conclude from this that the epsilon-globin gene is not regulated by competition with other genes in the human beta-globin locus. PMID- 2269428 TI - Lethal and temperature-sensitive mutations and their suppressors identify an essential structural element in U2 small nuclear RNA. AB - U2 snRNA is an essential component of the splicing apparatus in eukaryotic cells. Three possible secondary structures for the highly conserved 5' half of U2 snRNA are consistent with U2 phylogenetic sequence variation. To distinguish among these models and to test the function of U2 structural elements, we made greater than 35 mutations in the yeast U2 snRNA gene. Some of the mutations were designed in pairs so that combinations could be made that would restore base-pairing to differentiate helix requirements from primary sequence requirements. The mutations identify an essential stem-and-loop structure adjacent to the branchpoint interaction region. A conserved complementarity to the loop just upstream of the Sm site and an additional conserved stem-loop are dispensable for U2 function, even in the background of a previously identified large internal deletion. Non-Watson-Crick base appositions at the 53-62 base pair in the essential stem lead to a variety of temperature and KCl-sensitive phenotypes, as well as an accumulation of unspliced precursors in vivo. Chemical structure probing of U2 RNA in vivo reveals that the bulk of U2 in a yeast cell adopts a structure in good agreement with that deduced from genetic results. We suggest that this stem-loop is not a binding site for an intrinsic U2 snRNP protein but may interact with other factors during spliceosome assembly or splicing. PMID- 2269429 TI - DnaK, DnaJ, and GrpE heat shock proteins negatively regulate heat shock gene expression by controlling the synthesis and stability of sigma 32. AB - The Escherichia coli DnaK heat shock protein has been identified previously as a negative regulator of E. coli heat shock gene expression. We report that two other heat shock proteins, DnaJ and GrpE, are also involved in the negative regulation of heat shock gene expression. Strains carrying defective dnaK, dnaJ, or grpE alleles have enhanced synthesis of heat shock proteins at low temperature and fail to shut off the heat shock response after shift to high temperature. These regulatory defects are due to the loss of normal control over the synthesis and stability of sigma 32, the alternate RNA polymerase sigma-factor required for heat shock gene expression. We conclude that DnaK, DnaJ, and GrpE regulate the concentration of sigma 32. We suggest that the synthesis of heat shock proteins is controlled by a homeostatic mechanism linking the function of heat shock proteins to the concentration of sigma 32. PMID- 2269430 TI - Isolation and characterization of the ZWF1 gene of Saccharomyces cerevisiae, encoding glucose-6-phosphate dehydrogenase. AB - Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first step of the pentose phosphate pathway, a reaction that generates NADPH. We have isolated ZWF1, the Saccharomyces cerevisiae gene that encodes G6PD, and identified its transcript and transcription start point. Expression of ZWF1 appears not to be regulated, consistent with its 'housekeeping' role. Null mutants lacking G6PD appear to grow normally, but are more sensitive than wild type to oxidizing agents that presumably reduce the level of NADPH. This suggests that G6PD has a major role in NADPH production in yeast. Regulation of GAL1 expression appears normal in zwf1 mutants, suggesting that the pentose phosphate pathway is not involved in glucose repression. The predicted amino acid sequence of yeast G6PD is highly similar to the sequence of the Drosophila, human, and rat enzymes, except near its N terminus, where the yeast and Drosophila sequences diverge from that of human and rat. PMID- 2269431 TI - Negative regulatory elements of the Saccharomyces cerevisiae PHO system: interaction between PHO80 and PHO85 proteins. AB - The negative regulatory genes, PHO80 and PHO85, involved in transcriptional regulation of the yeast repressible acid-phosphatase-encoding gene, PHO5, have been cloned. Expression of PHO80 and PHO85 has been studied by means of lacZ fusions. We show here that these expressions are inorganic phosphate (Pi) independent and that they are controlled by the PHO80 gene product; moreover, PHO80 expression is controlled by PHO85. We also present genetic evidence for an interaction between the PHO80 and PHO85 proteins: increased PHO85 gene dosage partially compensates for the pho80-1 mutation and this effect is allele specific. The pho80-1 allele has been cloned and sequenced. The mutation changes Gly229 to Asp. This region was shown to be essential for PHO80 function by C terminal deletion analysis. PMID- 2269432 TI - A Candida albicans homolog of a human cyclophilin gene encodes a peptidyl-prolyl cis-trans isomerase. AB - A Candida albicans cDNA and its genomic counterpart were isolated from lambda phage libraries using a human T-cell cyclophilin (Cyp) cDNA as a hybridization probe. The clones contain a 486-bp open reading frame predicting a 162-amino acid, approx. 18 kDa protein which is similar in size to, and which shares 68 and 81% homology with, human T-cell Cyp and cytosolic Saccharomyces cerevisiae Cyp, respectively. Northern blots show the presence of a single mRNA species of about 800 bp. However, genomic Southern blots suggest the presence of at least one other Cyp-related gene in C. albicans. The cDNA was engineered for expression in Escherichia coli, and the resulting recombinant protein, like mammalian Cyps, exhibited a peptidyl-prolyl cis-trans isomerase (PPIase) activity which was sensitive to inhibition by cyclosporin A in vitro. These results indicate that the gene which we have cloned encodes a C. albicans Cyp. We designate this gene CYP1 (cyclophilin). Interestingly, the predicted C. albicans protein contains only two cysteine residues which do not align with any of the four cysteines conserved among mammalian Cyps. This suggests that the PPIase catalytic mechanism may not involve an enzyme-bound hemithioorthoamide, as previously reported for porcine Cyp. PMID- 2269433 TI - A tissue-specific puff (Balbiani ring a) in Chironomus thummi may contain a gene encoding a 67-kDa protein which exhibits non-tissue-specific expression. AB - A 2.3-kb genomic clone has been isolated from the region where the tissue specific puff, Balbiani ring a (BRa), is found on chromosome IV of the special lobe of Chironomus thummi salivary gland cells. The clone was characterized by nucleotide sequence analysis. Two clusters of direct tandem repeats were identified, as well as large and small open reading frames (ORFs). The large ORF was fused to an Escherichia coli lacZ gene. Antibodies against the beta galactosidase/ORF fusion protein reacted selectively on Western blots with a 67 kDa protein. Western-blot analysis and immunoelectron microscopy showed that this protein was distributed in the cells of all larval tissues examined. We concluded that BRa, a tissue-specific puff, whose activity correlates with the synthesis of 160-kDa secretory protein [Kolesnikov et al., Chromosoma 83 (1981) 661-677], may also contain a gene which is not expressed in a tissue-specific manner. PMID- 2269434 TI - Photoprotein aequorin: use as a reporter enzyme in studying gene expression in mammalian cells. AB - Aequorin is a luminescent protein present in the jellyfish Aequoria victoria which emits light (at 460 nm) in the presence of Ca2+. We report here that aequorin can be used as a reporter enzyme to monitor gene expression in eukaryotic cells. A cDNA encoding apoaequorin was fused to several eukaryotic promoters, including those of SV40, RSV and the HSV-1 tk gene, and introduced into several cell lines such as CV-1, COS and HeLa. At appropriate times after transfection, the aequorin activities in cell extracts were measured by monitoring the intensity of light emitted at 460 nm when triggered by Ca2+ by the use of a photomultiplier photometer. The aequorin assay was shown to be as sensitive as the conventional CAT assay, and the relative activities of various promoters estimated by the aequorin assay were in general agreement with those obtained by the CAT assay. The aequorin assay can be done within 6-7 h from the preparation of extract to the measurement of activity without using radioactive compounds. PMID- 2269435 TI - Vargula hilgendorfii luciferase: a secreted reporter enzyme for monitoring gene expression in mammalian cells. AB - The small marine ostracod crustacean, Vargula hilgendorfii, produces a bright blue luminous secretion which is ejected into seawater. The luminescence is due to a simple enzyme-catalyzed reaction involving only luciferase, luciferin (substrate), and molecular oxygen. Thus, V. hilgendorfii luciferase (VL) should be useful as a reporter enzyme in studies of gene expression in mammalian cells. Expression plasmids consisting of VL cDNA (vl) linked to the promoters simian virus 40 early region, Rous sarcoma virus long terminal repeat, human elongation factor, or mouse granulocyte colony-stimulating factor were introduced into a series of mammalian cell lines. Following transfection, VL activities in cell extracts and culture media were determined by a rapid light emission assay with V. hilgendorfii luciferin. Parallel experiments were carried out with the chloramphenicol acetyltransferase (CAT)-encoding gene. In all cell lines tested, VL was secreted, allowing the reporter activity to be determined directly from a small aliquot of the culture medium. The results indicate that the secreted VL enzyme is superior to CAT, firefly luciferase, and bacterial luciferase as a convenient and versatile indicator of gene expression in mammalian cells. PMID- 2269436 TI - Gene conversion and splice-site slippage in the argininosuccinate lyases/delta crystallins of the duck lens: members of an enzyme superfamily. AB - Argininosuccinate lyase(ASL)/delta-crystallin is a prominent example of an enzyme crystallin with roles as both a catalyst and a major structural component of the eye lens in birds and reptiles. In chicken it appears that gene duplication and separation of function may have occurred with one gene product acting primarily as a crystallin and one primarily as an enzyme. However, two delta-crystallin encoding genes are abundantly expressed in the lens of the embryonic duck (Anas platyrhynchos) which has extremely high ASL activity. Here the isolation and sequence analysis of full length cDNA clones for both duck delta-crystallins are described. The two delta-crystallins are highly similar (94% identical in predicted aa sequence), probably as a result of gene conversion. However, the cDNA for duck delta 2-crystallin contains an in-frame insertion of two codons, probably the result of a recent intron boundary slippage. ASL/delta-crystallin belongs to a superfamily of lyases, including fumarases, aspartases and adenylosuccinate lyase which possess some highly conserved blocks of aa sequence. There may be some clues to the tertiary structures of these conserved motifs in otherwise unrelated proteins for which three-dimensional structures are known. PMID- 2269437 TI - Random silent mutagenesis in the initial triplets of the coding region: a technique for adapting human glutathione reductase-encoding cDNA to expression in Escherichia coli. AB - The introduction of random silent mutations into the 5'-coding region of a human cDNA as the basis for successful expression in Escherichia coli is demonstrated in four steps. (1) Plasmid pUB200 containing the pRpL promoters of phage lambda was found not to serve as an expression vector for a unchanged human glutathione reductase (hGR)-encoding cDNA. (2) When this cDNA was expressed in a two-cistron context using high-copy-number plasmids, recombinant protein was detected in low yield (0.03% of the total cell protein). (3) Silent mutations were introduced into the triplets coding for the N-terminal amino acids. When screening E. coli colonies transformed with expression plasmids containing cDNA mutants, we identified adapted clones that produced hGR in up to 70-fold higher yield than the clone containing the unchanged cDNA. Sequence analyses of adapted cDNA species revealed lower G + C contents in the modified regions, suggesting altered mRNA structures. (4) When the adapted cDNA sequences were recloned in the vector which had failed to express unchanged hGR cDNA in step 1, synthesis of recombinant protein was as high as in step 3. This means that the yield of expression for adapted cDNA was at least 1000-fold higher than for unchanged cDNA. In conclusion, random silent mutations introduced into the translation initiation region of cDNA might be a useful technique for designing sequence features which favour gene expression. PMID- 2269438 TI - Prevalent and rare mutations among Gaucher patients. AB - Sequence analysis of gcs cDNA (encoding glucocerebrosidase) or genomic fragments originated from Gaucher patients revealed novel mutations. Two rare mutations were found in a type-2 non-Jewish Gaucher patient: a G----A transition (Gly325--- Arg) at nucleotide (nt) 5306 of the active gene and a T----G transversion (Cys342 ---Gly) at nt 5357. These mutations were not found in any other patient. A G----C transversion (Asp409----His) at nt 5957 was identified in two non-Jewish patients, and was designated TL. Two recombinant alleles were found. One recombinant allele designated recTL contained four single-nt mutations. These mutations included: (1) a G----C transversion at nt 5957 (Asp409----His) (the TL mutation); (2) a T----C transition at nt 6433 (Leu444----Pro) creating a new NciI site (NciI mutation); (3) a G----C transversion at nt 6468 (Ala456----Pro; 456 mutation); and (4) a G----C transversion at amino acid (aa) 460 (nt 6482), not associated with any aa change. Sequence analysis indicated that at least part of exon 9, intron 9 and exon 10 of the recombinant gene derived from the pseudogene. The other recombinant gene, designated recNciI, contained a mutation at aa 444 (NciI mutation), and mutations 456 and 460 described above; at least exon 10 of this gene originated from the pseudogene. We hypothesize that the presence of the pseudogene close to the active gene causes transfer of mutations into the active gene via gene conversion or nonhomologous recombination, thus accounting for the high frequency of mutations observed in the gcs gene. PMID- 2269439 TI - Isolation of the REC2 gene controlling recombination in Ustilago maydis. AB - The rec2 mutant of Ustilago maydis is defective in DNA repair, induced allelic recombination, and meiosis. We cloned the REC2 gene by complementing the radiation-sensitive phenotype of the mutant using a genomic DNA library. The transcript of the REC2 gene was identified as a 2.8-kb damage-inducible RNA. PMID- 2269440 TI - Ribosomal RNA of the primitive eukaryote Giardia lamblia: large subunit domain I and potential processing signals. AB - The cytoplasmic ribosomal RNA (rRNA) from the intestinal protozoan, Giardia lamblia, is unusually short; the large subunit (LS) and small subunit RNA and the 5.8S RNA are only 70-80% of the length found in typical protozoa, and are even smaller than most of their prokaryotic counterparts. Flanking regulatory DNA and processed rRNA sequences are similarly compact in size. To shed light on the origins and implications of this 'minimal' rRNA, the nucleotide sequence encoding the 5.8S RNA and domain I of LS RNA was determined. Secondary structure analysis revealed that an evolutionarily variable internal hairpin is partially 'deleted' in G. lamblia 5.8S RNA; the 3'-terminal pairing with LS RNA is conserved. Previously characterized eukaryotic 'expansion' regions are extensively shortened within the LS RNA; in one case, a hairpin is precisely 'deleted'. The short sequences flanking the mature 5.8S RNA that are removed by RNA processing (ITS1 and ITS2) are C-rich; our analysis suggests that the sequence GCGCCCC, in a hairpin configuration, may function as the processing signal. PMID- 2269441 TI - Sequence of a sea urchin hsp70 gene and its 5' flanking region. AB - We report the nucleotide sequence of a 4470-bp fragment derived from a sea urchin genomic clone containing part of a heat-shock protein 70 (Hsp70)-encoding gene. This fragment, named hsp70 gene II, contains 1271 bp of the flanking region and 3299 bp of structural gene sequence interrupted by five introns and encoding the N-terminal 371 amino acids (aa) of the protein. The 5' flanking region contains a putative TATA element, two CCAAT boxes, four heat-shock consensus sequence elements (hse) and one consensus sequence for binding of Sp1. Remarkable homologies were observed for deduced aa sequence and intron-exon organization between hsp70 gene II and rat hsc73 gene. PMID- 2269442 TI - High-level synthesis of biologically active human plasminogen activator inhibitor type 1 (PAI-1) in Escherichia coli. AB - Segments of a cDNA encoding human plasminogen activator inhibitor type 1 (PAI-1) were subcloned into a highly regulated and inducible Escherichia coli expression system. A plasmid encoding the mature form of human endothelial PAI-1 produced a functional recombinant molecule, as indicated by its ability to inhibit tissue plasminogen activator's enzymatic activity. In contrast to PAI-1 isolated from human fibrosarcoma cells, the biological activity of the recombinant PAI-1 was not dependent on pretreatment with denaturing agents. A construct encoding a polypeptide lacking the first 80 amino acids of PAI-1 also produced elevated levels of the truncated recombinant protein. However, this truncated product was functionally inactive, indicating that an intact N terminus is required for activity. PMID- 2269443 TI - Nucleotide sequence of the 5'-flanking region of the mouse k-FGF oncogene exhibits an alternating purine:pyrimidine motif with the potential to form Z-DNA. AB - The nucleotide sequence of the 5'-flanking region of the mouse k-FGF oncogene has been determined. This sequence extends 2.1 kb upstream from the transcriptional start point (tsp) and includes two Sp1 and two AP-2 consensus binding sequences immediately 5' of the TATA box. In addition, the sequence contains an alternating purine:pyrimidine motif that lies approx. 1 kb upstream from the tsp. PMID- 2269444 TI - Molecular cloning and deletion of the gene encoding aspergillopepsin A from Aspergillus awamori. PMID- 2269445 TI - Production and characteristics of the exocellular polysaccharide of a mutant Mycobacterium strain. AB - Mutant strains of Mycobacterium sp. V-649 producing highly mucous colonies on a solid cultivation medium were prepared after treatment with N-methyl-N'-nitro-N nitrosoguanidine and production of the exocellular polysaccharide was tested. The strains were cultivated in media with suitable sugar sources under submerged conditions. It was found that Mycobacterium sp. V-649/15 produces a maximum of 15 19% polymer after a 5-6-d cultivation. Gas chromatography indicated that the exocellular polysaccharide produced by this strain is of glucan type. PMID- 2269446 TI - Preparation of protoplasts and regeneration of intact cells of Streptomyces cinnamonensis. AB - Protoplasts were prepared and intact cells were regenerated in Streptomyces cinnamonensis--a monensin producer--to make genetic manipulations with this strain possible. 70-80% of protoplasts were formed and up to 90% of them could regenerate into intact cells. PMID- 2269447 TI - Vitamins as effectors of monensin production by Streptomyces cinnamonensis. AB - Vitamins added to submerged Streptomyces cinnamonensis cultures stimulated the production of monensins. Vitamins B2, B3, B5 and B12 enhanced the production by about 50%, vitamins B1 and B6 by 100%. The addition of biotin in optimal concentration resulted in more than 3-fold increase in total production. PMID- 2269448 TI - Observations on the structure and histochemistry of the skin of Mystus gulio (Ham.) (Osteichthyes: Siluriformes, Bagridae). AB - The skin of Mystus gulio (Ham.) is typical of siluroids in not having any scales. Large number of mucous cells and sacciform granular cells, interspersed with taste buds, were found in the epidermis. Histochemical tests showed the presence of weakly sulphated mucopolysaccharides in the mucous cells, while the sacciform granular club cells were found to be proteinaceous, with a small amount of lipids and phospholipids. The dermis is composed of a stratum laxum and a stratum compactum. The subcutis was found to consist of loosely arranged collagen fibres and fat cells. PMID- 2269449 TI - The morphological picture of implanted foetal rat brain tissue. AB - The authors studied the morphological picture of implanted foetal brain tissue. Macroscopically, they found that the grafts used for morphological study had taken in every case and that the size of the graft had doubled or trebled. The surface of the implant grew above the level of the recipient's cortex and numerous branching blood vessels were observed in the graft-cortex contact area. In the light microscope, organization of the cells in circular clusters or strips was found in the implant. Large numbers of blood vessels of varying calibre were present in the vicinity of large cell concentrations. Distinct differences between the cytoarchitectonics of the normal tissue of the recipient and the graft tissue were seen. Cells with a normal appearance or an apolar form, whose nucleus contained irregularly scattered chromatin and mosaic-like nucleoli, were observed at ultrastructural level. The nuclear membrane was thrown into multiple folds which invaginated deep into the nuclear matter. The Golgi complex covered a large area. Axodendritic synapses indistinguishable from the control were found in the neuropil. No changes were observed in the walls of the capillaries. The pericapillary zone was characterized by the presence of light astrocyte processes. PMID- 2269451 TI - The action of stabilizing selection on the perfection of new characters in evolution. AB - In birds, fusion of the carpal elements to a carpometacarpus during morphogenesis takes place during the evolutionary process at different rates, i.e. heterochronically, in different groups (developmental radiations), like the elements of the nasal apparatus in Sauropsida. This is because new characters spread and are pushed back at different rates from the terminal to the initial levels of morphogenesis. The shift is most likely automatic, in that it does not require further mutation, but it is set in motion by selection. Selection does not take effect only when an adequate character (which at first is very imperfect) is accepted; it also causes the character to grow, pushes it back towards the threshold of morphogenesis and thereby increases its perfection and its fitness. The path along which the shift takes place is determined by the morphogenetic route of recapitulation of the ancestral structure and since this movement is caused by protracted stabilizing selection, we can describe it as orthoselective movement. This means that recapitulation is flexible. At the same time, cellular and epigenetic interactions with surrounding structures are reciprocally influenced. The shift continues until adequate adaptation and perfection have been achieved. Stabilizing selection then ceases to act. The shift shows the evolutionary trend or further developmental possibilities. Its chief role is probably in the development of specializations. PMID- 2269450 TI - Ultrastructural changes in the brain capillaries after hypoxia. AB - The authors describe ultrastructural changes in and around rat brain capillaries after hypoxia. The experimental animals breathed a mixture of 5% oxygen and 95% nitrogen for two or for three hours; a third group, which spent three hours in this atmosphere, was treated 24 h later. Cytoplasm processes and vesicles were observed on the luminal side in the endothelial cells, while the cytoplasm contained vacuoles and altered mitochondria. The basement membrane of the brain capillaries was uneven and longitudinal clear zones were formed in it. Altered mitochondria were present in the pericytes and astrocytes. The most pronounced changes were found in the astrocyte processes, which were light and hydrated and contained destroyed mitochondria and lamellar bodies resembling myelin. After 24 h, morphological changes still persisted, especially in the astrocyte processes. PMID- 2269452 TI - Comparative cytoarchitectonics of the parabrachial nuclear complex in mammals. AB - The cytoarchitectonics of the parabrachial nuclear complex (PBNC) were studied in brain stem sections, stained with cresyl violet, from laboratory and phylogenetically interesting mammals. In all the animals studied, the PBNC can be separated into the following subnuclei: dorsal (D), dorsomedial (DM), dorsolateral (DL), lateral (L), medial (M), ventral (Ve) and the less distinct interstitial subnucleus (I). According to the nomenclature used hitherto, D, DM, DL, I and L belong to the ncl. parabrachialis lateralis (or dorsalis) and M and Ve to the ncl. parabrachialis medialis (or ventralis). In most laboratory animals (rodents, the rabbit), the individual subnuclei are roughly all the same size. In other phylogenetically interesting mammals, however, the size of some subnuclei deviates from the laboratory animal "norm". A comparison among these animals shows that in higher primates three of the six parabrachial subnuclei are enlarged. In insectivores the subncl. lateralis and subncl. medialis are also enlarged--possibly as an expression of a definite phylogenetic trend. In the discussion, the previously known connections of the PBNC are included and it is shown that each subnucleus has its characteristic connections. PMID- 2269453 TI - Note on variability of the arteries of the lower extremities in man. AB - The organization of the arterial bed was evaluated in the arteriograms of 253 lower extremities of subjects of a known sex and age. High origination of the a. profunda femoris from the a. iliaca ext. was observed in 0.4% of the cases; in 0.8% the a. profunda femoris arose from the transition of the a. iliaca ext. to the femoral artery. The crural segment was the most variable part of the arterial bed of the lower limbs. Most frequently, in 21.7% of the subjects, anomalies of the crural arteries were unilateral; in 4.6% they were bilateral. In 2.3%, bilaterally different anomalies were present. The a. tibialis post. is the most variable crural artery and the a. peronea is the most stable. PMID- 2269454 TI - The v. portae of the domestic cat and variability of its tributaries. AB - In the domestic cat the v. portae originates as a thick venous trunk below the liver through confluence of the v. gastrica sinistra, v. lienalis and v. mesenterica cranialis. It was formed in this way in 19 cases, i.e. in 63.3%. Among the aberrations found in the other cases, the most frequent was a common trunk for the v. gastrica sinistra and v. lienalis (6.7%). In 26 cases (86.6%), the v. gastrica sinistra was an independent tributary of the v. portae. A single v. lienalis was found in 27 cases (90.0%). Inter-organ anastomoses were found in the region of the v. lienalis. In 29 cases (96.7%) they connected the cranial part of the spleen with the fundus ventriculi. Inter-organ venous anastomoses between the caudal part of the spleen and the pancreas were found in four cases (13.4%). These anastomoses came from within the spleen and joined the veins of the stomach or the pancreas. In 14 cases (46.6%) the v. mesenterica cranialis originated as the v. colica dextra or v. caecalis. In nine cases (30.0%), in the concavity of the small intestine we found two trunks forming the v. mesenterica cranialis-one from the caecum and the other from the ileum and jejunum. Lastly, in five cases (16.7%) the v. mesenterica cranialis started only from the ileum and jejunum. The most frequent first tributary-in 19 cases (63.3%)-was a venous trunk of varying length formed by union of the v. mesenterica caudalis and the v. colica media, which started in 11 cases (36.7%) as the v. colica dextra.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269455 TI - Veins of the large intestine, stomach and pancreas of the domestic cat and their variability. AB - Most frequently - in 19 cases (63.3%) - the v. colica media was a tributary of a trunk, formed together with the v. mesenterica caudalis, which emptied into the v. mesenterica cranialis. In two cases (6.7%) it emptied independently into the v. mesenterica cranialis. In 25 cases (83.3%) the v. mesenterica caudalis arose from the rectum and, at colon ascendens level, acquired one or more vv. colicae sinistrae. In six cases (19.8%) the v. colica dextra opened into the v. ileocolica and in eight cases (26.7%) it was the initial tributary of an independent v. ileocolica which joined the v. mesenterica cranialis directly. The drainage of venous blood from the stomach is organized as follows: the fundus region is connected to the v. lienalis by means of inter-organ anastomoses. The curvatura minor is drained by means of the v. gastrica sinistra. Venous blood from the region of the curvatura major ventriculi flows partly into the v. lienalis (by way of the vv. gastroepiploicae or small veins) and partly into the v. gastrica sinistra. Drainage of venous blood from the pancreas: a v. pancreaticoduodenalis cranialis was present in 16 cases (53.3%) and a typical v. pancreaticoduodenalis caudalis was found in 12 cases (40.0%). Simultaneous formation of both vv. pancreaticoduodenalis, with a possible incidence of small venous efferents to the v. lienalis, was observed in only nine cases (30.0%). In 21 cases (70%), blood from the region of the flexura duodenojejunalis was drained by the last v. jejunalis; in other cases it drained into the vv. pancreaticoduodenales.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269456 TI - Variability of ramification of the a. mesenterica cranialis in the domestic rabbit (Oryctolagus cuniculus f. domestica). AB - The authors studied the ramification of the a. mesenterica cranialis and its variability in 30 domestic rabbits (Oryctolagus cuniculus, f. domestica, breed New Zealand White). The animals were anaesthetized and red-dyed latex was injected into their arterial bed via the thoracic aorta. In every case (100%), the a. mesenterica cranialis was an independent trunk arising from the abdominal aorta 1.5-2 cm caudally to the origin of the a. coeliaca. We did not observe a truncus coeliaco-mesentericus in our material. In 17 cases (56.7%), the a. pancreaticoduodenalis caudalis was the first branch of the a. mesenterica cranialis. In 28 cases (93.3%) it formed a thick trunk which divided into two main branches to the aboral part of the duodenum and the caudal part of the pancreas respectively; in two cases (6.7%), the a. pancreaticoduodenalis caudalis was duplicated. In only two cases (6.7%), the first branch of the a. mesenterica cranialis was the a. colica media. The a. mesenterica cranialis then divided into two thick trunks to the intestine - the truncus jejunalis and the truncus ileocaecocolicus. Single aa. jejunales branched off successively from the arching truncus jejunalis. The truncus ileocaecocolicus led in a caudal direction and broke up, as a rule, into three arteries supplying the ileum, the caecum and the colon transversum. In 17 cases (56.7%), 1-6 aa. jejunales arose directly from the trunk of the a. mesenterica cranialis and 13-21 from the convexity of the arch of the truncus jejunalis. In 13 cases (43.3%), all the aa. jejunales found (11-23) were branches of the truncus jejunalis. On the mesenteric side of the jejunum, the aa. jejunales forked and formed an arcade from which small branches led to the intestine. In the rabbit we always observed only one arcade; more complex systems were not formed. A truncus ileocaecocolicus, whose branching was characterized by marked variability, was found in all 30 cases (100%). Division of this trunk to an a. ileocaecalis, a. caecocolica and a. colica dextra was observed in only four cases (13.3%). In every case, extensive anastomoses with branches of the a. colica dextra and a. colica sinistra were formed. In general, it can be claimed that the arterial bed of the a. mesenterica cranialis is highly variable. Since little attention has been paid in the literature to variability of the ramification of this artery in different species of mammals, the authors will concentrate, in their next studies, on a detailed investigation of the arterial bed of the abdominal cavity, and of its variability, in further laboratory animals. PMID- 2269457 TI - On the validity of von Baer's laws in evolutionary morphology. AB - The validity of von Baer's "laws" on the general and the specific in vertebrate morphogenesis (especially organogenesis) was varified. The author starts from the hypothesis that the rudiments of traits newly acquired during morphogenesis are not rigid, not immovable, during morphogenesis, but that the action of protracted stabilizing selection during the geological ages causes them to spread and pushes them back to the perfected and stabilized in adulthood, thereby shortening the recapitulation of ancestral traits, which may eventually disappear below the threshold of detectable morphogenesis. On the basis of this thesis of the dynamics of evolutionary morphogenesis (the author bases his considerations on his studies of the morphogenesis of the avian carpometacarpus and the nasal apparatus in Sauropsida), the author comes to the conclusion that these von Baer's rules presuppose rigidity and immovability of phylogenetic morphogenesis. In fact, the general and the specific in evolutionary morphogenesis (especially organogenesis) is continuously motion, the general changes to the specific and the specific to the general and both categories undergo incessant changes. Von Baer's rules are thus not generally valid, they cannot rank as laws and in many cases they do not apply to morphogenesis (especially organogenesis), particularly in the transitional phase of evolutionary morphogenesis, when the rudiments of progressive evolutionary deviations have reached the early phases of morphogenesis and recapitulation has disappeared - and the "general" has also disappeared. PMID- 2269458 TI - Origin of the v. portae and variability of its tributaries in laboratory animals. II. The guinea pig (Cavia aperea f. porcellus). AB - The authors investigated the origin of the v. portae and variability of its main tributaries in 30 adult guinea pigs (Cavia aperea f. porcellus). The venous bed was visualized by means of blue-dyed latex. The v. portae was formed the most frequently - in 17 cases (56.7%) - by the confluence of three veins - the v. mesenterica cranialis, the v. lienalis and the v. gastroepiploica dextra; less often it was formed from four or five tributaries and in one case only it was formed by union of the v. mesenterica cranialis and the v. lienalis. The v. gastrica sinistra was a tributary of the v. lienalis in 24 cases (80.0%). It arose on the ventral and the dorsal surface of the stomach, in the region adjacent to the curvatura minor ventriculi. In 21 cases (70.0%) it was joined by an independent v. cardiaca. The v. lienalis originated in the hilus lienis, usually as a result of the union of two venous trunks. Inter-organ anastomoses were found in 26 cases (86.7%); in 10 cases (33.3%) they occurred simultaneously between the spleen and the stomach and between the spleen and the pancreas, while in 16 cases (53.3%) they connected the superior pole of the spleen with the stomach. An independent v. gastroepiploica dextra was present in 19 cases (63.3%) as a tributary of the v. portae. In 22 cases it was joined by the v. pylorica. A v. pancreaticoduodenalis cranialis was present in 27 cases (90.0%). In 18 cases (60.0%) it united with the v. gastroepiploica dextra to form a common trunk, the v. gastroduodenalis, which joined the v. portae; in two cases (6.7%) it was an independent tributary of the v. portae. In six cases it was connected with the v. lienalis and in three cases (10.0%) it was replaced by a few vv. pancreaticae emptying into the v. lienalis. A typical v. pancreaticoduodenalis caudalis, as a tributary of the a. mesenterica cranialis, was found in 19 cases (63.3%). In two cases, together with the v. pancreaticoduodenalis cranialis, it formed a single trunk (the v. pancreaticoduodenalis communis). A comparison of the v. portae and its tributaries in the guinea pig and the cat has so far not brought to light any significant morphological differences relative to their different zoological classification and their different modes of life. PMID- 2269459 TI - Cholinergic innervation of the endocrine cells of the blood vessels of the human brain. AB - In an immunochemical study of the melanocytes of the brain blood vessels in man, the presence of vasopressin has been demonstrated. The endings of cholinergic axons terminate on the surface of these cells. It is assumed that the melanocytes participate in regulation of the motility of the arteries of the brain. PMID- 2269460 TI - Catecholamines and indolalkylamines of the pia mater and spinal cord in vertebrates. AB - Fluorimetric methods were used to determine adrenaline, dopamine, noradrenaline, serotonin and tryptamine in the pia mater of the brain and spinal cord of various vertebrates (fishes, birds, mammals) and of man. The histochemical method using glyoxylic acid showed the presence of biogenic monoamines in adrenergic nerve fibres and in the monoaminocytes. Their total amount in the pia mater is roughly the same, except in man, in whom it is significantly lower. From the higher adrenergic axon concentration on the one hand and the lower number of monoaminocytes on the other, it can be concluded that the neuronal factor has a more important role in the regulation of brain haemodynamics in man. PMID- 2269461 TI - Provoked laryngeal dysfunction. PMID- 2269462 TI - Acoustic evaluation of laryngeal pathology. PMID- 2269463 TI - Results of vocal therapy for phononeurosis: behavior approach. PMID- 2269464 TI - Changes in neuromuscular irritability in balbuties of children and adolescents. PMID- 2269465 TI - [Speech training by "visible speech":development and evaluation of a new system]. PMID- 2269466 TI - Complex mechanism of laryngeal phonation. A. Description of activity. PMID- 2269467 TI - Complex mechanism of laryngeal phonation. B. Analogue pattern of the larynx. PMID- 2269469 TI - Human monoclonal antibodies to C, c, E, e and G antigens of the Rh system. AB - A panel of heterohybridomas secreting human IgG and IgM monoclonal antibodies to the C, c, G, E, and e antigens of the Rh system has been established. Both classes of antibody have been shown to react with red blood cells carrying their respective antigens; those of the IgM class being able to directly agglutinate unmodified red blood cells in saline. The heterohybridomas have been shown to be suitable for bulk culture and produce levels of antibody in the range of 15-73 micrograms/ml in the spent culture supernatant. PMID- 2269468 TI - Human rheumatoid synovial cell stimulation by the membrane attack complex and other pore-forming toxins in vitro: the role of calcium in cell activation. AB - The effects of non-lethal amounts of a variety of pore-forming agents on cultured human rheumatoid synovial cells (HRSC) have been investigated. Non-lethal complement membrane attack and non-lethal amounts of melittin, perforin and ionomycin all caused a biphasic release of prostaglandin E2 (PGE2) from HRSC, an early phase of release occurring within 1 hr and a second larger phase commencing after 4 hr and continuing over the 24-hr time-course. Removal of extracellular calcium abolished the release of PGE2 under all conditions of non-lethal attack. Modulation of G-protein activity reduced the second phase of release caused by non-lethal doses of the membrane-attack complex (MAC) from 800 ng/10(6) cells PGE2 to around 300 ng/10(6) cells. Non-lethal levels of the MAC also caused release of interleukin-6 (IL-6) from HRSC over the 24-hr time-course, with levels reaching 550 ng/10(6) cells at 24 hr compared to background levels of 200 ng/10(6) cells. No detectable release of IL-1 alpha could be measured at any time following non-lethal complement membrane attack. These results suggest a role for the MAC as an initiating mediator inducing the inflammation associated with rheumatoid arthritis. PMID- 2269470 TI - The specificity of the human neutrophil IgA receptor (Fc alpha R) determined by measurement of chemiluminescence induced by serum or secretory IgA1 or IgA2. AB - Heat or chemically aggregated IgA or IgG stimulated degranulation of neutrophils with comparable efficiency. The same aggregates induced a neutrophil respiratory burst which could be measured by lucigenin-enhanced chemiluminescence. Serum IgA1 or IgA2 coated onto microtitre plates were both capable of inducing a respiratory burst in neutrophils, as was secretory IgA1 or secretory IgA2. All bursts were of similar size for a given concentration of IgA and were greater than the burst elicited by an equivalent concentration of IgG. For each subclass of IgA the respiratory bursts were dependent on their density on the opsonized surface. Since monomeric and dimeric forms present in secretory IgA preparations both elicit a respiratory burst in neutrophils, secretory component and J chain cannot block the receptor binding site on the Fc region. The potential of secretory IgA to act as an opsonin might have important consequences on mucosal surfaces where the availability of complement components is limited. PMID- 2269471 TI - Frequency and phenotypic feature of autoantibody-producing cell precursors in the preclinical stage of murine lupus. AB - The present study addresses the question of whether there is a difference in the frequencies of autoantibody-producing B-cell precursors in healthy compared with lupus-prone mouse strains. Spleen mononuclear cells (MNC) from 4-week-old (i.e. at the preclinical stage of lupus) mice were activated in vitro for 3 and 6 days with lipopolysaccharides (LPS) and the numbers of IgG, IgA and IgM autoantibody producing cells were analysed by the ELISPOT assay. The results indicate a high frequency of IgM autoantibody-secreting cells after both 3 and 6 days in vitro stimulation. In spite of high frequencies of IgG-producing cells appearing late during the course of LPS stimulation, no IgG or IgA autoantibody producing cells were detected. No significant differences in the autoantibody repertoire were noted between healthy and lupus-prone mice, indicating that independent of the genetic background the immune system has the capacity to react with autoantibody production. Phenotypic analysis of LPS-induced, IgM-secreting B cells showed clearly that the majority of them were surface IgM+, CD5+ but Thy-1-. PMID- 2269472 TI - Adoptive transfer of viable motheaten (mev) humoral autoimmunity: IgM to IgG switch of the hyperglobulinaemia in nude, beige recipient mice. AB - Homozygous C57BL/6 nude, beige mice (B6 nu,bg) were used as recipients for the transfer of lymphoid cells from autoimmune homozygous B6 'viable motheaten' mice (B6 mev) and from either normal B6 mice (B6 wild) or B6 bg mice as controls. Surprisingly, the mev cell grafts prolonged survival of these short-living doubly immunodeficient recipients. Although the [mev----nu,bg] chimeras did not develop the mev external necrosis phenotype, they showed a hyperglobulinaemia and a significant increase of their anti-single-stranded DNA (ssDNA) antibody titres, compared to control chimeras ([bg----nu,bg] and [wild----nu,bg]). However, this hyperglobulinaemia was quite different from the mev-type hyperglobulinaemia, with poor contribution of the IgM isotype. Moreover, the anti-ssDNA antibodies were more distributed among the various Ig classes than the anti-ssDNA antibodies of the mev homozygous mice. Though the adoptive transfer of some mev-type humoral autoimmunity symptoms were achieved in this chimera model, the recipient mice did not suffer from the several other features of the mev syndrom, such as the severe pathology and the extremely high IgM serological levels. PMID- 2269473 TI - Distinct regulation of humoral and cellular immunities to hepatitis B surface antigen. AB - The surface envelope protein of hepatitis B virus (HBsAg) stimulates the immune system to produce anti-HBs antibodies and to generate cell-mediated immunity. These two arms of immunity were found to be regulated differently in bm12 (H 2bm12) or CBA and C3H (H-2k) mice. In bm12 mutant (I-A beta mutant of B6 mice) mice, the anti-HBs production, early-type, and immune complex-type hypersensitivity were impaired, but the delayed-type hypersensitivity and the T cell proliferation in vitro were normal compared to the parental B6 (H-2b) mice. The mutation of the A beta molecule seems to affect the immune responses differentially. On the other hand, C3H or CBA mice produced anti-HBs antibodies after major S protein (pre-S-depleted HBsAg) stimulation, but could not generate the hypersensitivity responses. The pre-S region could circumvent the non responsiveness of the hypersensitivity response in C3H and CBA mice. These data suggest that the humoral and cellular immunities to the HBsAg particle are regulated distinctly and are affected by either the A beta molecule of the host or the pre-S region of the HBsAg. PMID- 2269474 TI - Re-evaluation of the chemotactic activity of tumour necrosis factor for monocytes. AB - The present study was designed to re-evaluate the chemotactic activity of recombinant tumour necrosis factor (TNF) and lymphotoxin (LT). TNF and LT induced migration of human monocytes across polycarbonate filter in a 90-min assay. Preincubation with FMLP rendered monocytes unresponsive to subsequent exposure to the same chemoattractant. FMLP-desensitized monocytes retained full responsiveness when exposed to TNF as chemotactic stimulus. The converse was observed when monocytes were deactivated specifically to TNF. FMLP receptor antagonists did not interfere with TNF chemotaxis. A monoclonal anti-TNF antibody inhibited the chemotactic activity of recombinant TNF. These results indicate that, under the experimental conditions utilized here, TNF elicits chemotaxis of human monocytes. PMID- 2269475 TI - Critical role of the C-terminus in the biological activities of human tumour necrosis factor-alpha. AB - Alterations of the C-terminal amino acid sequence of human tumour necrosis factor alpha (hTNF-alpha) caused significant changes in its biological activity. Thus shortening of the C-terminus by removal of two or three amino acids led to a very marked loss of cytotoxic activity. Other, more subtle changes introduced by site directed mutagenesis resulted in a less drastic reduction in cytotoxicity. The mitogenic activity towards human fibroblasts of the hTNF-alpha was reduced in parallel with the loss of cytotoxicity. These results suggest that the C-terminal amino acids of hTNF-alpha are critical for its biological actions and that they may be part of the receptor-binding site. PMID- 2269476 TI - Human intravenous immunoglobulin modulates monokine production in vitro. AB - The effects of human immunoglobulin preparations for intravenous use (IVIg) on in vitro-induced monokine production were studied. Individual peripheral blood monocytes, obtained from healthy blood donors, which produced interleukin-6 (IL 6) and tumour necrosis factor-alpha (TNF-alpha) after in vitro stimulation, were identified by cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescence technique. Lipopylosaccharide (LPS) or Borrelia burgdorferi spirochetes (Bb) were used to induce TNF-alpha and IL-6 production in cultures. Peak synthesis occurred 2.5 hr after initiation of the cultures in the majority of the monocytes, but not at all in lymphocytes. The monocytes were identified by two-colour staining using a monocyte-specific mAb. IL-6 was produced by 64 +/- 8% or 71 +/- 9% (means +/- SD) of the non-IVIg-exposed monocytes after LPS or Bb stimulation, respectively (n = 12). A dose-dependent and significant reduction of the number of IL-6-producing cells was noted in the IVIg-supplemented cultures (P less than 0.003). In these cultures 24 +/- 12% or 29 +/- 12% of the monocytes made IL-6 in response to LPS or Bb. Kinetic studies indicated a sustained significant inhibition of IL-6 production during 24 hr of culture (P less than 0.001). In contrast, TNF-alpha synthesis was not inhibited by IVIg. LPS or Bb stimulation resulted in 47 +/- 18% or 69 +/- 7% TNF-alpha producing cells versus 48 +/- 9% or 59 +/- 8% in IVIg-supplemented cultures. These results indicate down regulation of IL-6, but not TNF-alpha production, by IVIg. A direct antigen neutralization is an unlikely explanation for the divergent effects observed on monokine production after IVIg addition. PMID- 2269478 TI - The function of high endothelial venules in mouse lymph nodes stimulated by oxazolone. AB - The effects of antigenic stimulation on the expansion of T-cell dependent areas in lymph nodes of mice were studied in relation to the effects on high endothelial venules (HEV) located in this area. Lymph nodes regional to areas of skin that had been treated with solutions of oxazolone were studied at several time-points after stimulation. The following measurements were made relative to lymph nodes of untreated animals: (i) the expansion of the T-cell dependent areas in combination with the increase of HEV in this area, as detected by the HEV specific mAb MECA-325, using morphometric analysis: (ii) the influx of FITC labelled lymphocytes from the blood into the lymph node by FACS: (iii) the capacity of HEV to bind lymphocytes using an in vitro binding assay. Morphometry showed that T-cell dependent areas increased rapidly after stimulation with oxazolone and although the mean area of MECA-325-positive HEV had also increased, this increase lagged behind the expansion of the T-cell area. Therefore the amount of HEV per T-cell area in an antigen-stimulated lymph node was smaller than in an untreated lymph node and correlated with the percentage of FITC labelled cells that had entered it. In a lymph node from an oxazolone-treated animal this percentage was decreased to the same order of magnitude as the area of HEV per T-cell area, but the overall binding capacity of HEV was not affected by oxazolone treatment. Antigenic stimulation therefore leads to a rapid expansion of the potential sites of lymphocyte entry into a lymph node, but the efficiency of the HEV does not change. PMID- 2269477 TI - Anti-bacterial activity of peritoneal cells from transgenic mice producing high levels of GM-CSF. AB - Two lines of transgenic mice carrying the gene for granulocyte-macrophage colony stimulating factor (GM-CSF) produce vastly increased numbers of macrophages with abundant foamy cytoplasm resembling classical activated macrophages. Cells from both lines were negative for myeloperoxidase, a bactericidal enzyme found in monocytes as well as neutrophils, but not mature macrophages. Cells from the so called 'male line' produced greatly increased levels of oxygen degradation products in response to phagocytosis, compared with cells from the 'female line' or from normal littermates. The ability of the cells to phagocytose and lyse the intracellular bacterium Listeria monocytogenes was tested in vitro using radiolabelled organisms. Although the cells from transgenic mice were more highly phagocytic than cells from normal littermates, cells from either line were no more efficient than normal at lysing the bacteria they had phagocytosed. Nevertheless, because of the high phagocytic rate, more bacteria were exposed to lysis in the cells of transgenic mice, and the final outcome was a higher rate of bacteriolysis. PMID- 2269479 TI - The lysis of cytotoxic T lymphocytes and their blasts by cytotoxic T lymphocytes. AB - After binding to their targets, cytotoxic T lymphocytes (CTL) deliver a lethal hit signal, ultimately leading to target cell lysis, and then can recycle to lyse additional targets, without themselves being destroyed. If non-specific secreted lytic mediators are involved in such lysis. CTL survival would not be expected unless the effectors are immune to CTL-mediated lysis. Therefore the lytic susceptibilities of alloimmune peritoneal exudate lymphocytes (PEL), containing up to 50% CTL, and of the cytolytic PEL blasts (PEB), obtained by culturing with interleukin-2 (IL-2), were examined. 51Cr-labelled BALB/c (H-2d) anti-EL4 (H-2b) (d alpha b) PEL were lysed 88%, 78%, and 48% by C3H/eb (H-2k) anti-P815 (H-2d) (k alpha d) PEL, C57BL/6 (H-2b) anti-P815 (b alpha d) PEL and b alpha d PEB, respectively. Similarly, b alpha d PEL were lysed 82% and 21% by d alpha b PEL and PEB, respectively. b alpha d PEB were lysed 82%, 28-39% and 39-51% by k alpha d PEL, b alpha d PEL and b alpha d PEB, respectively, b alpha d PEB were lysed 29 55% by d alpha b PEL. Furthermore, the CTL-containing populations were no less susceptible to lysis than normal lymphocytes. Since the majority (80-90%) of cells in these two types of CTL-containing populations can be directly and specifically lysed by appropriately immunized PEL CTL, we conclude that both the lytic granule and perforin lacking (PEL) and containing (PEB) CTL are not a priori immune to CTL-mediated lysis. These findings are in accord with theories proposing lysis to be induced by receptor-mediated contact between effector CTL and target cells, and challenge those suggesting the involvement of secreted lytic mediators. PMID- 2269480 TI - Establishment of functional T cells in SCID mice does not lead to termination of pregnancy. AB - Syngeneic (CB20) thymus and spleen T cells transferred to SCID mice, and shown to be present by flow cytometric analysis and functional by their ability to reject third-party skin grafts, do not lead to a detectable failure of syngeneic or allogeneic pregnancy. Unless the small number of B cells contaminating the T-cell innocula are capable of mounting a blocking antibody response, it is concluded that these results show that a humoral ('blocking antibody') response is not essential for successful pregnancy. PMID- 2269482 TI - Role of anti-IgG autoantibodies in kidney transplantation. AB - To demonstrate whether anti-IgG autoantibodies of different isotypes and specificities play a role in kidney transplantation, pretransplant sera of recipients (a) with well-functioning grafts (n = 40); (b) with reversible rejection episodes that were treated successfully (n = 63); and (c) with irreversible graft rejection (n = 40) were tested for four different anti-IgG autoantibody activities. A protective effect of IgG-anti-F(ab)2 gamma antibodies on graft survival was observed (p less than 0.01). High pretransplant IgG-anti-Fc gamma activity was found to be associated with a low kidney graft survival rate (p less than 0.02). Pretransplant IgM-anti-F(ab)2 gamma and IgM-anti-Fc gamma activities showed no effect on kidney graft outcome. PMID- 2269481 TI - Further characterization of the EAI factor induced by alloimmunization for treatment of recurrent abortion. AB - In order to remove the EAI "blocking" activity, EA inhibition positive sera from patients with recurrent abortions were absorbed after alloimmunization with paternal lymphocytes by the lymphoblastoid cell line (LCL) of the husband. To avoid non-specific binding via the Fc-receptor, the cells were first fixed with 0.05% glutaraldehyde. Absorption was performed for 3 h at 4 degrees C. For subsequent elution, the cells were incubated with 0.1 M glycine-HCl, pH 2.3, for 30 min at 4 degrees C. After each step, EAI assay was carried out to determine the "blocking" activity in the supernatants. Furthermore, 10% SDS-PAGE and immunoblotting with goat antihuman IgG of the whole serum and the supernatants were performed. The results obtained give evidence that the EAI "blocking" activity can be absorbed by and eluted from the LCL of the immunizing husband, and is due to an IgG antibody directed against an antigen present on the LCL. Further absorption experiments with trophoblast cells will show whether this antigen is also displayed by the trophoblast. PMID- 2269483 TI - Functional and immunogenetic characterization of FcR-blocking antibody. AB - The characteristics and functional importance of FcR-blocking antibodies and their production were investigated after immunization with whole blood, "buffy coat" and purified platelets. We studied the presence of FcR-blocking antibody in haemodialyzed, transfused patients waiting for kidney transplantation, and we found strong correlation between the blocking effect and better graft survival. We suggest that this blocking antibody does not attack FcR as primary target. Investigation of blocking activity of ten different immune sera on 50 healthy panel cells showed that target antigen has some polymorphic varieties. On basis of family studies it seems that the target antigen is not linked to HLA haplotype. The blocking effect of sera could be removed by absorption of CD8+ cells, B lymphocytes, platelets and granulocytes, but not with erythrocytes, monocytes, CD8- cells and NK cells. PMID- 2269484 TI - Long-lasting kidney graft survival after immunization with antibody-coated blood cells: mediation by immunosuppressive autoantibodies. AB - Treatment of LEW rats before transplantation with BN blood cells preincubated with LEW-anti-BN serum resulted in prolonged BN kidney graft survival (untreated, 8 +/- 0.4 days; pretreated, 124 +/- 36). The serum of pretreated animals contains a factor which suppresses T cell proliferation against donor antigens. This effect was not mediated by antiidiotypic antibodies because it was reproduced in a donor-unrelated system. The serum and IgG of pretreated animals also suppressed the humoral immune response. As for T cells, the antibody-suppressive effect was not donor-restricted. A broadly reactive anti-immunoglobulin (anti-B cell) autoantibody was found in the IgG fraction of immunized animals. The mediation of immunosuppression by broadly reactive anti-B and T cell autoantibodies induced by the immunization with antibody-coated blood cells is discussed. PMID- 2269485 TI - In vitro studies on lymphocyte Fc gamma receptor blocking factors in human renal transplantation. AB - In this study we have confirmed our earlier observation that the presence in pre transplant serum of a high-molecular-weight lymphocyte Fc gamma receptor blocking factor correlates with improved human renal allograft survival. This factor was found to bind preferentially to B cells and to impair B cell function in vitro. PMID- 2269486 TI - Polyclonal stimulation of human B lymphocytes derived from fetal liver and spleen cells at different stages of ontogeny. AB - The functional capacity of human lymphocytes derived from fetal liver and spleen at different stages of ontogeny (16-34 weeks of gestation) was studied using in vitro models (increase in cell volume, [3H]thymidine incorporation, Ig secretion) reflecting various stages of activation induced by mitogens (LPS, PWM) in vitro. Lymphocytes differed in their reactivity to LPS depending on the period of intrauterine development: cells from the early liver could respond with enhanced IgM production whereas lymphocytes derived from this organ after more than 25 weeks failed. The opposite was found to apply to spleen cells: only lymphocytes derived from the organ after more than 25 weeks showed significant LPS-induced in vitro differentiation. These data were in correlation with the proliferative response to LPS. It was clear that the number of CD20-positive mature B cells in the lymphocyte preparations was not responsible for these results, since comparable yields were found throughout the period of fetal development of the liver studied, whereas in the spleen increasing numbers of B cells were seen. PMID- 2269487 TI - Involvement of interleukin-1-like factor(s) in type II collagen-induced arthritis in mice. AB - To explore the role of interleukins in development of arthritis, we induced collagen-induced arthritis in mice and examined interleukin activities in the inflamed joints. Arthritis developed in 90% of mice 4-5 weeks after primary immunization with type II collagen. Joint extracts from mice with collagen induced arthritis contained high levels of interleukin 1 (IL-1)-like activity but not interleukin 2 (IL-2) or interleukin 4 (IL-4) activity. IL-1-like activities in the lesions were correlated with development of arthritis assessed by joint swelling and erythema. These results suggest that IL-1-like factor(s) may participate in the etiopathogenesis of collagen-induced arthritis in mice. PMID- 2269488 TI - In vitro antigen-binding properties of coelomocytes of Eisenia foetida (Annelida). AB - Annelids are capable of cellular and humoral defence reactions against foreign antigens. The main aim of this study was to characterise the antigen-binding properties of coelomocytes of Eisenia foetida by means of quantitative autoradiography and direct measurement of radioactivity. It was found that the antigen-binding capacity was significantly increased after antigen stimulation. Furthermore, the preincubation of coelomocytes with non-labelled proteins reduced the binding of radiolabelled antigen. The highest level of inhibition was found when the same protein was used for preincubation. These results indicate that antigen-binding properties are to some extent specific. PMID- 2269489 TI - A high molecular weight cytotoxic lymphokine in supernatants of lymphokine activated killer cells cross-reacts with transforming growth factor beta. AB - Supernatants of lymphokine-activated killer (LAK) cells were highly cytotoxic for melanoma A375 cells. A high-molecular-weight fraction was isolated from such supernatants by gel filtration on an S-300 Sephacryl column (Fraction 1; Fr1). The cytotoxic activity in Fr1 was heat- and acid-resistant and was completely abolished by a rabbit antibody against TGF-beta. We conclude that Fr1 contains TGF-beta or a cross-reactive molecule, associated with a high-molecular-weight carrier. PMID- 2269490 TI - Sequence similarity between human immunodeficiency virus type 1 envelope protein (gp120) and human proteins: a new hypothesis on protective antibody production. AB - The production of neutralizing antibodies against the central portion of HIV-1 gp120 requires cooperation between T cell and B cell epitopes of this region. We found a motif common to the carboxyterminus of the second conserved region of HIV 1 gp120 and sequences of some human proteins, most of which participate in immune response. The sequence of gp120 of HTLV-IIIB with the highest T-cell reactivity incorporates this motif. It is suggested that the existence of this sequence motif in the central region of the HIV-1 gp120 molecule prevents the production of neutralizing antibodies against the virus in humans. PMID- 2269491 TI - Perceptions and attitude towards tobacco smoking among doctors in Chandigarh. AB - Two hundred and eighteen randomly selected doctors drawn from among the faculty and students of Postgraduate Institute of Medical Education and Research; Interns and staff at the General Hospital; and General practitioners of the Chandigarh city, were administered a structured questionnaire. Among them 31.6% were current smokers whereas 23.3% had stopped smoking (ex-smokers). All but one of the smokers were men who smoked cigarettes. Spirit of experimentation and peer influence were important initiating factors whereas the habit was continued mainly to concentrate on work/study. Doctors were uniformly aware of the detrimental effects of smoking, particularly its association with lung cancer, chronic bronchitis and coronary artery disease, and this was the major reason for their abstaining or wanting to quit the habit. The relation of smoking with oral cancer, laryngeal cancer, emphysema and peripheral vascular disease was not well appreciated. Counselling patients about hazards of smoking was practised significantly less often by smoking doctors and surgeons. The options favoured by doctors for preventing smoking included a ban on tobacco advertising, specific health warning on cigarette/bidi packs, and restriction of smoking in public places, particularly hospitals and clinics. PMID- 2269492 TI - Bilateral simultaneous pneumothorax--a study of 25 cases. AB - Twenty-five cases of bilateral simultaneous pneumothorax were studied. In children it was mostly postpneumonic, whereas in adults it was tuberculous or traumatic. Prompt intercostal drainage on both the sides supported by antibiotics and/or anti-tubercular drugs, and respiratory physiotherapy was curative on most occasions. The association of bronchopleural fistula or septicaemia worsens the prognosis. PMID- 2269493 TI - Pulmonary functions in tropical pulmonary eosinophilia. AB - Abnormalities in pulmonary functions in a group of ten patients with tropical pulmonary eosinophilia were analysed. Mild obstruction was observed in four, restrictive pattern in three, combined defect in one and two had normal study. Except in one patient in whom mild obstructive defect persisted, functions in all others reverted to normal on treatment with diethylcarbamazine. PMID- 2269494 TI - Response of lung transfer components to grades of smoking. AB - Pulmonary functions were studied in 50 healthy, asymptomatic, 20 to 47 years, male smokers along with 50 healthy non-smokers matched for age, height, socio economic status and physical activity. Smokers consumed 2-30 cigarettes per day with duration of smoking ranging from 2 to 26 years. In smokers FEF, V75. PEF and MVV were significantly reduced whereas FRC was increased significantly. Pulmonary diffusion function as assessed by TLCO showed significant reduction. While Vc showed progressive decrease with increasing duration and quantity of smoking, DM increased in the beginning but gradually declined later. TLCO showed a better negative correlation with quantity than with duration of smoking even when the effect of other factors was excluded. Decrease in TLCO is probably due to bronchoconstriction and reflex vasospasm of pulmonary vasculature. Co-efficient of diffusion KCO was also decreased in smokers. PMID- 2269495 TI - Mediastinal masses due to extramedullary hematopoiesis. PMID- 2269496 TI - Bronchial foreign body masquerading as a lung carcinoma. AB - Three cases which presented with clinical and radiological features consistent with a diagnosis of lung neoplasm and eventually turned out to be due to a foreign body are described. Their management and outcome was different in each case. The value of making a firm histological diagnosis in bronchoscopically visible lesions prior to thoracotomy is emphasised. Multiple bronchoscopic examinations and biopsies may be needed to achieve a histological diagnosis. PMID- 2269498 TI - Systemic lupus erythematosus during isoniazid therapy. AB - A case of systemic lupus erythematosus (SLE) in a young female which developed during the course of isoniazid therapy for pulmonary tuberculosis is described. SLE in this case is believed either to be induced or precipitated by isoniazid. Pertinent literature has been reviewed. PMID- 2269497 TI - Persisting alveolitis in miliary tuberculosis despite treatment with short-course chemotherapy. AB - Bronchoalveolar lavages in two patients with miliary tuberculosis have shown lymphocytic alveolitis. A 6-month regimen with an initial intensive 2-month phase resulted in remarkable clinical and radiographic improvement in both. However, bronchoalveolar lavage following treatment has shown that there was a persistence of lymphocytic alveolitis, though with reduced intensity. The significance of the persisting alveolitis, despite treatment, is not known at present. There is also a suggestion that compartment-alisation of lymphocytes may occur in miliary tuberculosis of the lung. PMID- 2269499 TI - Tooth in the bronchus--an unusual foreign body and presentation. AB - Tooth in right bronchus in a 60-year-old man who presented with recurrent episodes of chest infection, dyspnoea and haemoptysis is a rare clinical entity. The patient was cured after successful bronchoscopic removal of the tooth. PMID- 2269500 TI - Pyopneumothorax associated with pneumopericardium. AB - An unusual association of pneumopericardium with pyopneumothorax is presented. Pneumopericardium responded after intercostal drainage. PMID- 2269501 TI - Short course chemotherapy (9 months) for lymphnode tuberculosis. AB - Eight-two patients with tubercular lymphadenitis received rifampicin, isoniazid and ethambutol for 9 months. Complete disappearance of glands after this period occurred only in 74.3% of cases. Extension of therapy upto 1 year showed clearance in 10 more cases with an overall response rate of 87.2%. It is concluded that 9 months of therapy with these 3 drugs is not satisfactory for tubercular lymphadenitis. PMID- 2269502 TI - Indirect haemagglutination test for the assay of antibodies against Japanese encephalitis viral antigen in human & animal sera. AB - The indirect haemagglutination (IHA) test was standardized for the assay of antibodies against Japanese encephalitis (JE) virus. Glutaraldehyde fixed sheep erythrocytes were sensitized with purified and concentrated JE vaccine (200-300% brain concentration). The JE vaccine made from Nakayama-NIH strain of JE virus was purified by protamine sulphate treatment and by ultracentrifugation in a sucrose gradient. The sensitized cells were quite stable in liquid as well as in lyophilized state both at -70 degrees C and 4-8 degrees C. These cells could be used for two years without much loss (4-8 times loss) in titre. The IHA test was as sensitive as the neutralization (N) test performed by plaque reduction method in chick embryo fibroblasts. The sensitivity of the test was influenced by the source of erythrocytes i.e., from the different sheep from which these were drawn. After standardization of the test, 16 human sera and 18 sera of immunized mice were assayed for antibodies against JE virus by N and IHA tests. There were no significant differences between titres of both human and mice sera determined by N and IHA tests (P greater than 0.05). The correlation coefficient between N and IHA titres for human sera was 0.60 (P less than 0.05) and for mice sera 0.82 (P less than 0.01). The IHA test has been found to be very simple, inexpensive, sensitive and reproducible. PMID- 2269503 TI - Isolation of Japanese encephalitis virus from Culex pseudovishnui Colless, 1957 (Diptera: Culicidae) in Goa. AB - A strain of Japanese encephalitis virus was isolated from a pool of 54 female C. pseudovishnui Colless, 1957. The mosquitoes were collected in August 1988 during the period of epidemic of JE. This is the first report of isolation of JE virus from mosquitoes in Goa in the western coastal belt of peninsular India. In view of this isolation, C. pseudovishnui acquires greater importance, even though its density and relative prevalence during the current study was found to be far lower than C. tritaeniorhynchus. PMID- 2269504 TI - Reduction in the dosage schedule of BPL-inactivated neural tissue vaccine for rabies prophylaxis in man. AB - There exist two different immunization schedules for neural tissue rabies vaccine (NTV) for human use in India, the amount of vaccine given by the schedule recommended by Central Research Institute (CRI), Kasauli, being higher than that recommended by Pasteur Institute of India (PII), Coonoor. A study was therefore undertaken to assess the feasibility of reducing the CRI dosage schedule for rabies prophylaxis. The antirabies antibody response in laboratory animals and human subjects following 7, 10 and 14 daily doses of NTV with or without administering rabies immune globulin (RIG) was much higher than the minimum protective level of 0.5 IU/ml of serum. Based on these results, the CRI schedule could be reduced from 14 x 5 ml of NTV to 10 x 5 ml in class II and class III rabies exposure cases. PMID- 2269505 TI - Prevalence of HBsAg carriers among some tribes of Madhya Pradesh. AB - Prevalence of HBsAg was determined in 1314 sera obtained from 11 different tribal populations of five districts of Madhya Pradesh. Reversed passive haemagglutination assay was used for screening showed a HBsAg carrier rate of 2.99 to 21.54 per cent among the various tribes. Significant regional variation was also observed. PMID- 2269506 TI - Monocyte/macrophage functions & humoral response in blood & bronchoalveolar lavage fluid of pulmonary tuberculosis patients. AB - Subsegmental bronchoalveolar lavage (BAL) was performed in 33 patients with active pulmonary tuberculosis and five control subjects. Phagocytosis by monocytes and alveolar macrophages was studied, and in addition serum and BAL immunoglobulin and complement levels were also determined. The phagocytic activity of blood monocytes was depressed in pulmonary tuberculosis patients as compared to controls, 37.8 +/- 2.3 per cent; 50.7 +/- 4.2 per cent and 32.9 +/- 3.6 per cent for sheep RBC's, latex and Staphylococcus aureus respectively compared to 66.7 +/- 6, 54.8 +/- 2.2 and 68.3 +/- 3.5 per cent respectively in controls; the differences being significant for sheep RBC's (P less than 0.05) and Staph. aureus (P less than 0.001). However, phagocytosis was not impaired in BAL macrophages (P greater than 0.05). In patients no significant alteration in serum immunoglobulin and complement levels was observed except that levels of C4 component of complement were increased in patients with far advanced lesions (98.5 +/- 33.7 mg/dl compared to 78.7 +/- 7.9 mg/dl; P less than 0.05). While IgM and C4 component of complement could not be detected in BAL fluid the levels of IgA were significantly increased in pulmonary tuberculosis patients (65.5 +/- 50.5 mg/dl compared to 39.9 +/- 13.3 mg/dl in control; P less than 0.05). Since IgA secreted in the BAL fluid is mostly synthesised locally, increased levels of this immunoglobulin could be of value in determining activity of the disease. PMID- 2269507 TI - Incidence of Gardnerella vaginalis infection in pregnant & non-pregnant women with non-specific vaginitis. AB - The occurrence of G. vaginalis in patients with non-specific vaginitis (NSV) was studied. Of the 200 women with vaginitis screened, 84 were diagnosed to have non specific vaginitis. G. vaginalis was isolated from 33 (39.28%) patients either alone or in combination with other organisms, while one of the healthy controls with no vaginal discharge yielded G. vaginalis on culture. The nature of vaginal discharge could not be correlated with the type of infection. Clue cells and amine test gave inconsistent results in the presence of G. vaginalis infection. A varying susceptibility pattern of G. vaginalis was observed against various antimicrobials, metronidazole (95%) and gentamicin (75%) showing highest sensitivity. PMID- 2269509 TI - Human enterocyte adhesion of enteroadherent Escherichia coli. AB - Esch. coli strains manifesting localised (17), diffuse (8) or aggregative (17) phenotypes of adherence to HEp-2 cells were tested for their ability to adhere to human enterocytes isolated from duodenal biopsies of adult volunteers to obtain further evidence of their enteropathogenecity. Esch. coli strains H10407+; CFAI+ and LT+ STp+ STh+, F 294 B; a localised adherent strain positive with entero adherent factor probe reported previously to attach to small intestinal enterocytes and F 582 C; LT- STp+ STh+ were the positive controls: H10407P (CFAI- mutant of H10407+) and K12 served as negative control strains. Adherence of variable degree was seen with 35.3 per cent of enteroaggregative Esch. coli (EAggEc) and with 58.8 per cent of enteroadherent Esch. coli localised (EAEC-L); EAEC-diffuse (EAEC-D) did not adhere to the human enterocytes. The possibility that EAgg EC and diffuse phenotypes may adhere better to lower small intestine or the large intestine, needs to be investigated. PMID- 2269508 TI - Mycoplasma hominis infections in female genital tract & use of immunofluorescence for antibody detection. AB - A total of 325 women with genital tract infection and 108 healthy controls were screened for the presence of mycoplasmas. Of these, 325 patients, mycoplasmas were recovered in 186. Thirty five isolates were M. hominis and 151 isolates of Ureaplasma urealyticum. The fluorescent-antibody technique (FAT) has been employed for the rapid identification of mycoplasma colonies growing on agar plates. The method was found to be rapid for detection of M. hominis growing on primary isolation plates. The antibody titre of patient's serum was also detected by FAT. Patients' sera were diluted four fold from 1:4 to 1:256 dilutions. In 7 patients fluorescence was seen with 1:16 serum dilution, in 18 with 1:64 dilution and in 3 with 1:256. The immunofluorescence test gave a sensitivity of 96.66 per cent, specificity of 95.0 per cent, with percentage of false negativity and false positivity being 3.45 and 5.0 per cent respectively. PMID- 2269510 TI - Prevention of malaria-induced foetal abnormalities following immunization of mice with Plasmodium berghei merozoite antigen. AB - Pre-pregnancy immunization of Swiss albino mice with merozoite antigen of P. berghei entrapped in multilamellar phosphatidyl choline liposomes resulted in (i) increased prepatent period, (ii) either no or low parasitaemic levels, (iii) reduced mortality, and (iv) normal foetal and placental development, upon challenge with P. berghei on 13th gestational day. The unimmunized animals which received either phosphate buffered saline or empty multilamellar phosphatidyl choline liposomes before pregnancy developed high parasitaemic and 30-40 per cent animals died before parturition while 60-70 per cent unimmunized animals revealed foetal abnormalities such as low body weight and larger spleen size. Placentae of unprotected animals had hyperplasia of trophoblastic membrane and plugging of placental sinusoids with parasitized erythrocytes and malarial pigments. The data suggest that prior immunization of animals with merozoite antigen entrapped in multilamellar phosphatidyl choline liposomes could abrogate the ill effects induced by malaria infection under the stress of pregnancy. PMID- 2269511 TI - Weedivorous fishes for the control of vectors of Malayan filariasis. AB - An attempt was made to assess the efficacy of phytophagous fishes viz., Ctenopharyngodon idella, the Chinese grass carp and Osphronemus goramy, the giant gourami in the control of mansonioides mosquitoes by checking the growth of aquatic weeds which support their breeding. When C. idella and O. goramy were used in monoculture 80.21 and 81.25 per cent of the ponds were kept free from weeds. With polyculture using grass carp in combination with other varieties of carps, only 70.10 per cent of the ponds were kept out from the reinfestation of weeds. Even in the reinfested ponds, there was significant reduction (P less than 0.05) in vector breeding in all the three types of piscicultures, as compared to the control ponds. The utility of weedivorous fishes in the elimination of aquatic weeds and thereby breeding of vectors of Malayan filariasis was thus demonstrated. PMID- 2269512 TI - Reactivity of Cryptococcus neoformans & Candida species with concanavalin A & blood grouping sera. AB - Forty strains of Cryptococcus neoformans, 30 of Candida albicans, 24 of C. parapsilosis and 10 strains each of C. tropicalis and C. (Torulopsis) glabrata were examined. A 0.2 per cent solution of concanavalin A (Con A) in phosphate buffered saline and commercial anti-A and anti-B blood grouping sera were used in the whole cell slide agglutination test. All the isolates of Candida species strongly reacted with Con A and over 90 per cent were agglutinated by anti-A and B blood grouping sera. In contrast, except for one strain, Cryptococcus neoformans did not agglutinate with Con A or blood grouping sera. These findings suggest, on one hand, a fundamental difference in the sugar mosaic of the cell surface components of Cryptococcus neoformans and Candida species, and on the other, presence of similar antigenic determinant(s)/receptors on the cell surface of Candida species and human erythrocytes. PMID- 2269513 TI - Cloning & expression of chikungunya virus genes coding structural proteins in Escherichia coli. AB - DNA complementary to the single stranded RNA genome of Chikungunya (CHIK) virus with poly A tract was cloned into the plasmid pGEM-3Zf(-) and 5Zf(+) by blunt end ligation strategy. Clones containing the cDNA inserts were selected by X-gal, IPTG system. They were tested for the expression of structural protein(s) of CHIK virus by in situ enzyme immunoassay and Western blot. The former assay system showed the presence of expressed viral proteins. Analysis of Western blot shows that three structural proteins, E1, E2 and capsid (C) are expressed in Esch. coli. The molecular weights of envelope proteins E1 and E2 were 44-46 Kd and 42 44 Kd respectively, which are lesser than the actual molecular weights of virional proteins (50-52 Kd). This may be due to the absence of glycosylation of these proteins in Esch. coli. In clone no. 382, a high molecular weight protein (56-58 Kd) was observed, which was probably the unglycosylated form of P62 polyprotein coded by the virus during its multiplication. A small protein of MW 6 8 Kd was also expressed in clone nos. 382 and 504, and this appeared to be the unglycosylated form of E3 protein of CHIK virus. PMID- 2269514 TI - Hypothermia: an unusual manifestation of Reye's syndrome. AB - A four year old girl manifested with seizures, raised intracranial tension and altered consciousness. Laboratory investigations suggested Reye's syndrome. Later she developed fatal hypothermia. Rarity of such a case is highlighted. Probable pathogenesis of hypothermia in Reye's syndrome is discussed. PMID- 2269515 TI - Alopecia with rickets: an end organ unresponsiveness to 1,25-dihydroxyvitamin D- a case report. AB - Two siblings of a rare syndrome of vitamin D dependent type II rickets are reported for the first time from India. The clinical and biochemical picture was characterised by florid rickets, alopecia, hypocalcemia and resistance to therapy with high dosages of vitamin D3. Due to lack of facilities for estimation of 1,25(OH)2D, alopecia remains the only clue to the diagnosis of this rare syndrome in association with resistant rickets. PMID- 2269516 TI - High serum cholesterol. PMID- 2269517 TI - Hyperlipidemic pancreatitis. AB - Marked elevation of triglyceride levels appears to be causally linked to acute pancreatitis and is found in 12% to 38% of patients presenting with acute pancreatitis. Elevated cholesterol levels are not associated with pancreatitis. The pathogenesis of pancreatitis associated with hypertriglyceridemia is not clear. Clinical recognition of this association is extremely important, because therapy with diet and lipid-lowering agents may prevent development of pancreatitis. PMID- 2269518 TI - Disorders of the pancreas. PMID- 2269519 TI - Computed tomography and acute pancreatitis. AB - Computed tomography (CT) is the best overall imaging modality in the clinical management of acute pancreatitis. It can detect complications such as phlegmonous extension outside the gland, abscess and pseudocyst formation, and hemorrhage. Pancreatic necrosis can be diagnosed with the use of dynamic CT scanning after the rapid bolus injection of iodinated contrast media. The information gathered can be used to guide clinical management and provide anatomic detail for percutaneous aspiration and drainage or surgical intervention when indicated. PMID- 2269520 TI - Idiopathic acute pancreatitis. AB - In most patients presenting with acute pancreatitis, the cause can be established on the basis of initial history, physical examination, laboratory studies, and abdominal sonography. Patients with unexplained pancreatitis at that point are often considered to have idiopathic disease. However, a cause and, often, effective treatment to prevent recurrent pancreatitis are possible in many of these patients if an aggressive diagnostic approach is taken to discover undiagnosed hyperlipidemia, occult gallstones, abnormalities of the bile and pancreatic ducts, sphincter of Oddi dysfunction, pancreatic cancer and other tumors, and cystic fibrosis (in children and young adults). PMID- 2269521 TI - Predictors of severity of acute pancreatitis. AB - This article summarizes the sensitivities, specificities, and predictive values of five types of predictors of severity of acute pancreatitis: the clinician's assessment, Ranson and modified Glasgow criteria, peritoneal tap, computed tomographic scan, and individual laboratory tests. PMID- 2269522 TI - Management of pseudocysts, inflammatory masses, and pancreatic ascites. AB - This article focuses on the masses and ascites that result from pancreatic disease, including sterile pancreatic phlegmons, sterile or infected pseudocysts, and infected pancreatic abscesses, and addresses their clinical significance and treatment. PMID- 2269523 TI - Pancreatic stones. AB - Pancreatic calculi, once considered pathologic and even "reportable," are frequently observed in patients with chronic pancreatitis. They are not to be considered pathognomonic of chronic alcoholism, because they are frequently observed in other types of chronic pancreatitis, such as the tropical, Afro Asian, hereditary, idiopathic, and senile varieties. The widely recognized concept that appearance of calculi indicates the end stage of the disease is challenged in this article. The subject of pancreatic lithogenesis is controversial, but pancreatic stone protein has been extensively studied by one major group. Techniques to remove calculi by endoscopy or extracorporeal shock wave lithotripsy are available, but it is not clear whether they serve only a cosmetic purpose or actually help in alleviating pain and arresting the progress of disease. PMID- 2269524 TI - The cause and management of the pain of chronic pancreatitis. AB - The cause of pain in chronic pancreatitis appears to be related to ductal and parenchymal hypertension and possibly to pancreatic ischemia. The management of pain needs a multidisciplinary approach. Medical measures such as abstinence from alcohol and therapy with mild analgesics are useful. Surgery should be considered when the pain begins to interfere with the patient's quality of life. Ductal drainage operations may be indicated when the duct is dilatated. The alternative is pancreatic resection, which, although safe and effective, creates diabetes when much of the pancreas is removed. Newer operations that relieve pain while preserving function are being devised. PMID- 2269525 TI - Chronic pancreatitis in the elderly. AB - Idiopathic senile chronic pancreatitis (CP) appears to be a special subtype of nonalcoholic CP. Main clinical features are onset after the age of 50 years, prevalence in men, a painless clinical course, marked weight loss associated with diarrhea (steatorrhea) or diabetes mellitus, and pancreatic calcific deposits. Idiopathic senile CP constitutes about two thirds of cases of nonalcoholic CP, but it is rare compared with the incidence of alcoholic CP. The relationship of idiopathic senile CP to the "normal" age-related morphologic and functional abnormalities of the exocrine pancreas is unknown. PMID- 2269526 TI - Diagnosis and preoperative evaluation of pancreatic cancer, with implications for management. AB - At present, diagnosis of pancreatic cancer can be achieved only in symptomatic patients. Better diagnostic and staging procedures, which include angiography, laparoscopy, and peritoneal cytology, allow a more accurate preoperative assessment of resectability and may spare the patient an unnecessary operation or provide him or her with the option of transfer to a specialized unit for a definitive operation with lower morbidity and mortality rates. PMID- 2269527 TI - Disorders of the pancreas in children. AB - Diseases of the pancreas in children are often congenital; the genetic basis of some conditions such as cystic fibrosis have been elucidated using molecular biologic techniques. Anatomic abnormalities in childhood that cause symptomatic pancreatic disease are usually treated surgically. The biochemical abnormalities found with enzyme deficiencies, CF, and Shwachman's syndrome are best treated with medical therapy. The most common cause of acute pancreatic injury in children is trauma. Chronic pancreatic insufficiency usually occurs secondary to CF. PMID- 2269528 TI - Endoscopic management of pancreatic disorders. AB - Endoscopic management of pancreatic diseases is a rapidly developing area. Many innovative techniques and types of equipment have become available. The indications for diagnostic and therapeutic intervention in may disease states are in evolution. Diseases such as acute gallstone pancreatitis, pancreatic cancer, and complications of chronic pancreatitis are being approached more aggressively. Controversy concerning application of these techniques is discussed in this article. PMID- 2269529 TI - Digitalis associated mortality in patients after a myocardial infarction: moral responsibilities in recommending clinical trials. PMID- 2269530 TI - Posture and the measurement of blood pressure. PMID- 2269531 TI - The gender gap: why do women live longer than men? PMID- 2269532 TI - Idiopathic restrictive cardiomyopathy in the young: report of two cases. AB - Two cases of idiopathic restrictive cardiomyopathy in young age are reported. This rare kind of restrictive cardiomyopathy is characterized by the absence of specific histologic features of myocardial abnormalities. In both cases (aged 12 and 9 years at diagnosis), the clinical picture was characterized by severe and slowly progressive congestive heart failure. The electrocardiogram showed biventricular hypertrophy, right bundle branch block and pseudoinfarctional Q waves. Echocardiography revealed moderate pericardial effusion, biatrial enlargement, and normal or nearly normal biventricular dimensions and systolic function. Cardiac catheterization disclosed the typically restrictive filling pattern. Right ventricular endomyocardial biopsy demonstrated moderate interstitial fibrosis and cellular hypertrophy without any evidence of infiltrative or storage myocardial disease or endocardial pathology. One patient underwent cardiac transplantation, whereas in the other, transplantation was contraindicated because of longstanding pulmonary hypertension and liver cirrhosis. The knowledge of this rare entity may correctly orient the diagnostic process in children suspected of having restrictive myocardial disease. Heart, or even heart-lung, transplantation must be considered in cases with congestive heart failure before irreversible damage occurs in many organs. PMID- 2269533 TI - Morphometric data concerning the great arterial trunks and their branches. AB - In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the vascular complex, that is the orifices of the great arterial trunks, ascending aorta, aortic arch, vessels branching from the aortic arch, the aortic isthmus, descending aorta, pulmonary trunk, orifices of the pulmonary arteries and arterial duct. In all, 17 different parameters were measured in each specimen, using several new parameters in addition to the measurements classically used in the aortic isthmus, arterial duct and pulmonary trunk. Anatomo-geometric models of these structures were developed, and stereometric formulas used to calculate the real volumes of the aortic isthmus, arterial duct and pulmonary trunk. The variations in the correlations between two measurable characteristics, that is, body weight and each of the morphometric parameters were analyzed, and the minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. The results show that the volume of the aortic isthmus increases by 0.03 ml for each millilitre increase in left ventricular volume. The isthmic volume increases by 0.32 ml for each millilitre increase in volume of the arterial duct and the volume of the pulmonary trunk increases by 6.4 ml for each increase of 1 millilitre in the volume of the aortic isthmus. The inner circumference of the aortic isthmus is greater than that of the arterial duct, whereas the former vessel is always shorter than the latter. We believe that these morphological data, when appropriately interpreted, have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders. PMID- 2269534 TI - Morphology of the region of the coronary sinus in respect to coronary sinus rhythm. AB - The arterial supply to the region of the coronary sinus and the interatrial septum was examined in 18 normal canine hearts. In 13 of a further 18 dogs, coronary sinus rhythm was evoked by the ligation of atrial arteries, subsequent to which the arteries were visualized by injection of latex. A stable coronary sinus rhythm is evoked by producing ischaemia in an extensive area of the right atrium, including the sinus node, the interatrial septum and Bachmann's bundle, but preserving from ischaemia the posteroinferior part of the right atrium. Microscopical examination of the hearts with coronary sinus rhythm, and comparison with 9 control hearts, failed to demonstrate any morphological centre, in the form of nodal cells, which might have been responsible for the abnormal rhythm. In the posterior part of the right atrium, the ischaemic changes failed to affect the approaches of the atrioventricular node. The approaches were predominantly composed of cells poor in myofibrils mixed to a variable degree with cells of the working myocardium. We discuss the possibilities of the development of coronary sinus rhythm and "circus movement" with regard to the participation of the approaches to the atrioventricular node. PMID- 2269535 TI - Effect of isoproterenol on induction of ventricular tachyarrhythmias in the normal and infarcted canine heart. AB - The influence of isoproterenol on induction of ventricular arrhythmias was evaluated in 10 normal dogs and 17 dogs with experimentally induced myocardial infarction. Programmed stimulation (using up to 6 extrastimuli) was performed before and then during infusion of isoproterenol (2 micrograms/minute followed by 4 micrograms/minute). Isoproterenol facilitated induction of sustained monomorphic ventricular tachycardia (cycle length 163 +/- 26 msec) in 5 of the 10 animals with no inducible baseline arrhythmia (P less than 0.05). Isoproterenol did not affect cycle length or the number of extrastimuli required in animals with baseline ventricular tachycardia (cycle length 158 +/- 15 msec before versus 163 +/- 17 msec during isoproterenol, P = 0.3; extrastimuli 3.8 +/- 0.6 before versus 3.8 +/- 0.4 during isoproterenol infusion, P = 0.3). Isoproterenol did not significantly facilitate induction of ventricular fibrillation in either normal dogs or those studied after production of myocardial infarction. We conclude that infusion of isoproterenol increases the incidence of inducible ventricular tachycardia in the infarcted heart, but does not facilitate the induction of ventricular fibrillation in infarcted or normal hearts, despite the use of an aggressive protocol for programmed stimulation. Isoproterenol is, therefore, a safe and useful adjunct to programmed stimulation in this setting. PMID- 2269536 TI - Reappraisals of atrioventricular node reentrant tachycardia: lessons learned from surgical treatment. AB - The exact site of reentrant circuit involved in the atrioventricular node reentrant tachycardia was questioned. Seven patients (6 females and 1 male), aged 21 to 64 years (mean = 40 +/- 17 years), with refractory nodal reentry, underwent surgical treatment. The associated cardiac diseases included rheumatic valvar disease in two and an atrial septal defect. Electrophysiologic studies before surgery showed dual nodal pathways in 4 patients. Right atrial endocardial mapping was performed and the earliest retrograde atrial activation during tachycardia was mapped to the apex of the triangle of Koch in 6 patients and near the orifice of coronary sinus in one. Perinodal dissection was performed according to the location of earliest retrograde atrial activity. Care was taken to preserve as much of the atrioventricular node and its arterial supply as was possible. Immediately after surgery, conduction in an antegrade direction recovered and the tachycardia could no longer be reproduced. There was no surgical mortality or morbidity. At 10 to 26 months of follow-up, all patients remain free of tachycardia without antiarrhythmic drugs. Four patients underwent repeated electrophysiologic studies at 2 weeks to 6 months after surgery. Dual nodal pathways were no longer demonstrated. It is concluded that the perinodal atrial tissue plays a part in the atrioventricular nodal reentry, and that surgical dissection is a simple and effective treatment for patients with refractory atrioventricular node reentrant tachycardia. PMID- 2269537 TI - Acute mitral regurgitation due to short periods of ischemia during percutaneous transluminal coronary angioplasty: an angiographic study. AB - The frequency and severity of mitral regurgitation were investigated during a short period of ischemia (60 seconds) in patients undergoing elective percutaneous transluminal coronary angioplasty of single vessel disease. Thirty patients showed stenoses in the left anterior descending artery, 3 patients in the circumflex artery and 1 patient in the right coronary artery. Only patients with global and regional normal left ventricular function, and without collaterals reaching or filling the target vessel, were enrolled in the study. All patients suffered pain during occlusion of the vessel. Signs of mitral regurgitation of grade 1 could be documented angiographically in 9 patients and of grade 2 in 4 patients. In no patient mitral regurgitation of grades 3 or 4 was seen. A highly significant (P less than 0.001) decrease of global, as well as regional, left ventricular function could be documented during ischemia in all patients. The breakdown of wall motion was more pronounced in patients with mitral regurgitation, and reached statistical significance (P less than 0.05) in the apical and anterolateral segments. All patients with mitral regurgitation showed extended severely hypokinetic or akinetic wall segments adjacent to the anterior papillary muscle. There were no angiographic signs of mitral valvar prolapse or dilation of the mitral annulus. We concluded that transient mitral regurgitation is common during short periods of ischemia in humans, but of only minimal degree in the setting of single vessel disease. The mechanism is different from mechanisms in chronic ischemic incompetence of the mitral valve. PMID- 2269538 TI - Long-term treatment with piroximone in patients with chronic heart failure. AB - The safety and efficacy of long-term oral piroximone therapy was assessed in 12 patients with chronic heart failure. Of these 12 patients, two died suddenly, and a further two were withdrawn because of worsening heart failure within 6 months while 8 completed the 1-year follow-up period. In 7 of these 8 patients, clinical evaluations showed sustained benefit, as demonstrated by significant increases in exercise tolerance. The remaining patient experienced a recurrence of severe heart failure at the end of follow-up. Twenty-four hour ambulatory electrocardiograms were compared in 9 patients before and during piroximone therapy. Aggravation of existing arrhythmias was observed in 3 patients, an amelioration in one with no change in the remaining 5. In the 5 patients in whom the hemodynamic effects of a single oral dose of 25 mg of piroximone were studied, the first dose resulted in a 20% increase in mean cardiac index and a 30% decrease in mean pulmonary capillary wedge pressure. This responsiveness to single-dose administration was maintained after 1-year follow-up. Likewise, comparison of the hemodynamic effects of four intravenous doses of piroximone revealed no significant difference in the response (n = 7), although the effects tended to be less marked at the end of follow-up. The present results suggesting that piroximone is effective and safe as adjunctive therapy in the management of patients with chronic heart failure will need to be confirmed in longer controlled trials. PMID- 2269539 TI - Reperfusion arrhythmias are rare during acute myocardial infarction and thrombolysis in man. AB - Coronary arterial reperfusion is commonly associated, in anaesthetized animals, with severe arrhythmias, but the clinical relevance of this model remains uncertain. Continuous electrocardiographic ST-segment recording was performed immediately from admission in 38 patients who presented within six (mean 2.5) hours of the onset of acute myocardial infarction and had emergency coronary arteriography and thrombolysis with intracoronary streptokinase. All patients received high doses of isosorbide dinitrate but no prophylactic anti-arrhythmic drugs. In 19 patients, 36 occurrences of intermittent reperfusion were observed. Stable reperfusion was achieved in 32 patients. Only 14 episodes of arrhythmia (11 ventricular) were observed in 6 patients within five minutes of transient or stable reperfusion. No episodes of arrhythmia were documented within five minutes of the other 57 occurrences of reperfusion. In contrast, 215 episodes of arrhythmia (198 ventricular) not associated with reperfusion were recorded in 32 patients. Arrhythmias are commonly observed in patients during evolving acute myocardial infarction and thrombolysis but are an insensitive and rarely specific marker of reperfusion at the time when this occurs. PMID- 2269540 TI - Prognostic role of inducible ventricular tachycardia in patients with dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia. AB - We studied the prognostic relevance of inducible ventricular tachycardia in 32 patients with dilated cardiomyopathy and spontaneous nonsustained asymptomatic ventricular tachycardia. Programmed ventricular stimulation included basic drive cycle lengths of 600, 500, 430, 370, 330 and 300 msec at single, double, and triple extrastimuli. Ventricular tachycardia (greater than or equal to 6 beats) was initiated in 7 patients (22%), with sustained monomorphic ventricular tachycardia being seen in 4 of them. During median follow-up of 21 months (13 44), 14 patients died. Sudden cardiac death occurred in two of the seven patients with inducible tachycardia and in only one of the 25 patients in whom it was not possible to induce tachycardia. Although patients with inducible tachycardia did not differ clinically from those in whom tachycardia could not be induced, the projected mean survival time was significantly shorter in those with inducible tachycardia (10 months vs. 32 months, P = 0.04). For late sudden cardiac death, the positive predictive value of inducible tachycardia was 28%. The negative predictive value was 96%. We conclude that induction of ventricular tachycardia by programmed stimulation might indicate poorer prognosis in patients with dilated cardiomyopathy. PMID- 2269541 TI - Electrophysiological effects of nicainoprol in patients with paroxysmal supraventricular tachycardias. AB - The electrophysiological effects of nicainoprol, a new class I antiarrhythmic drug, were evaluated in 29 patients with supraventricular reentrant tachycardias, due to accessory pathways in 15 and dual atrioventricular nodal pathways in 14 patients. Nicainoprol was administered intravenously as a bolus followed by continuous infusion of 1.5 mg/kg in two and of 2 mg/kg in 27 patients over one hour. Nicainoprol was given as a bolus of 1.5-2 mg/kg during sinus rhythm in 11 patients or during induced supraventricular tachycardia in 18. The drug successfully terminated the tachycardia in 17 patients due to block in the retrograde tachycardia limb in 15 and the antegrade limb in 2 patients. Prolongation of the cycle length preceded the termination in each case. In one case, the termination could not be achieved despite the administration of 3 mg/kg. The sinus cycle length, heart rate corrected QT interval as well as right atrial and right ventricular effective refractory periods remained unchanged. In contrast, the intranodal and infranodal conduction times, as well as QRS duration, were prolonged significantly. In patients with dual atrioventricular nodal pathways, there was a significant (P less than 0.05) increase of the effective refractory periods of the anterograde slow pathways. The changes of the anterograde fast pathways, however, did not reach significance level. More pronounced effects were found on effective refractory periods of the retrograde pathways, which were blocked in 4 patients and significantly (P less than 0.05) prolonged in the remainder. Similarly, in patients with accessory pathways the effect on the retrograde conduction was more marked with complete block in 5 patients and significant prolongation of effective refractory periods and shortest paced cycle lengths in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269542 TI - Effects of the inotrope DPI 201-106 on cardiac performance following cardiac surgery. AB - The haemodynamic, cardiac metabolic and electrocardiographic effects of the intravenous inotropic agent DPI 201-106, in 20 and 40 milligram doses, were studied in patients after coronary arterial bypass grafting. The patients were randomly allocated to receive placebo or DPI 201-106. Those receiving the active drug received either the 20 or the 40 milligram dosages of DPI 201-106. Both the placebo and the active drug were infused over 20 minute periods. Two baseline readings confirmed haemodynamic stability, and readings were taken immediately following the infusions and then at 20 minutes and at 40 minutes afterwards. Comparison of all the haemodynamic and metabolic data did not reveal any significant intra or inter group differences. Comparison of the electrocardiographic data revealed some differences. Patients receiving DPI 201 106 showed prolongation of the QTc interval immediately following the infusions. Changes in ST segments and T waves were observed. Independent analysis of the affected electrocardiographs reported that the changes were suggestive of, but not pathognomonic of, myocardial ischaemia. The metabolic data showed that the electrocardiographic changes were not associated with any evidence of anaerobic metabolism. The indication for DPI 201-106 as a positive inotropic agent in patients following coronary revascularization surgery was not established. PMID- 2269543 TI - Familial aggregation of defects of the left-sided structures of the heart. AB - A family is described where a mother and her three children had left heart defects. Three members of a second family were also noted to have such defects. This experience adds support to the hypothesis that in some families, such defects may have an incidence of recurrence higher than the 3% predicted by a multifactorial model. PMID- 2269544 TI - Myocarditis and myocardial interstitial fibrosis in constrictive pericarditis--an extended pathological spectrum? AB - We performed endomyocardial biopsy in six patients with constrictive pericarditis, revealing the presence of myocarditis and myocardial interstitial fibrosis in all regardless of the endocardial thickening. These findings suggest that the presence of endomyocardial involvement in the setting of restrictive heart disease should not be deemed specific for endomyocardial fibrosis when the clinical evaluation suggests constrictive pericarditis. PMID- 2269545 TI - Thrombolytic therapy for a patient with systemic lupus erythematosus and acute myocardial infarction. AB - A young patient with systemic lupus erythematosus was admitted to our hospital because of acute myocardial infarction, and treated by thrombolysis. Coronary angiography revealed a significant stenosis of the left anterior descending artery, together with an intraluminal thrombus. Clotting studies demonstrated an anticoagulant factor suggestive of lupus erythematosus. We conclude that thrombolytic therapy can be useful in patients with systemic lupus erythematosus who present with acute myocardial infarction, although some caution is needed in treatment. PMID- 2269546 TI - Colour Doppler flow mapping in the diagnosis of traumatic ventricular septal defect. AB - The use of colour Doppler flow mapping allows noninvasive diagnosis and gives haemodynamic information on the severity of ventricular septal defects. We describe the case of a man with delayed presentation of a traumatic ventricular septal defect in whom colour Doppler flow mapping permitted conservative management after accurate noninvasive diagnosis. PMID- 2269547 TI - Activity of cardiac enzymes measured in the coronary sinus in acute myocardial infarction. AB - Three patients with acute infarction of the anterior wall of the heart underwent catheterisation of the coronary sinus. Samples were taken for estimation of activity of cardiac enzymes. A small gradient was demonstrated between the sinus and the venous blood, suggesting that the coronary sinus is the conduit by which these enzymes are liberated into the systemic circulation. PMID- 2269548 TI - Isolated rheumatic carditis, a disease in search of diagnostic criteria. AB - We report a case of acute dilated cardiomyopathy with histologic proof of inflammatory myocarditis. Although immunosuppressive therapy seemed to induce the resolution of the inflammatory infiltrate, it had no effect on the clinical course. The diagnosis of isolated rheumatic carditis was considered because of the finding of a very high antistreptolysin O titre and lack of evidence for either viral disease, infection with group C and G streptococci or other causes of spuriously high titres of anti-streptolysin O. In view of our conclusion longterm chemoprophylaxis was instituted. PMID- 2269549 TI - Future research needs in policy, prevention, and treatment for drug abuse problems. AB - This paper outlines major research issues for the areas of illicit drug use. Research questions are posed for the following areas: (1) epidemiology and etiology; (2) social policy development; (3) prevention; and (4) treatment. PMID- 2269550 TI - The anthropologist as alcohologist: qualitative perspectives and methods in alcohol research. AB - As research disciplines differ from each other in terms of their epistemological and theoretical assumptions, they differ in the kinds of data they produce. This paper discusses the particular perspectives and methods that anthropologically produced data contribute to a biopsychosocial paradigm of alcohol use/pathology. Strategic uses of qualitative research approaches are suggested, and situations in which qualitatively produced data would be especially useful in the design and delivery of alcohol-related services are identified. PMID- 2269551 TI - Ethnic specification, validation prospects, and the future of drug use research. AB - Interest in drug use among America's major ethnic minority groups is rapidly increasing. Despite the welcomed interest, researchers tend to use broad ethnic labels to identify their samples. Such labels as "ethnic glosses" provide little information concerning the heterogeneity of each ethnic group and, in most instances, violate the guidelines concerning appropriate descriptions of sample characteristics. Use of broad ethnic descriptors particularly in drug use research creates external validity problems and prevents replications. Researchers are encouraged to obtain detailed information on the sociocultural characteristics of their samples by obtaining measures on ethnic identification, situated identity, and acculturative status. Use of ethnic identity and acculturation measures, however, can create problems in defining appropriate sample frames. PMID- 2269552 TI - Drugs and Iran after the Islamic revolution: prophesying the next quarter century. AB - Prior to the Islamic revolution of 1979, research on Iran's long-standing drug use patterns had begun in clinic settings, but there were few data available on countrywide use. Opium, the traditional drug used in social settings and produced in quantity in the east of the country, was the first target of fierce antidrug measures in 1979. The course of future drug cultivation, use, treatment and, therefore, research needed on the drug problem is closely linked to political developments in Iran. Much will depend on whether Iran maintains an independent stance or rejoins the international agencies' efforts. PMID- 2269553 TI - Research priorities for drug and alcohol studies: the next 25 years. AB - This paper identifies likely important research directions in drug and alcohol studies during the next quarter century. The discussion focuses first on several emergent trends in contemporary research which have the potential to make crucial contributions both to our general understanding of psychoactive substance use and associated disorders, and to the promotion of international public health. Implications of these developments for future research agendas are discussed, including the study of drugs, alcohol, and AIDS; prevention strategies; problem rates; and the study of traditional and modern uses of psychoactive substances. PMID- 2269554 TI - Critical aspects of the psychodynamics of substance abuse and the evaluation of their application to a psychotherapeutic approach. AB - A model of psychotherapy is proposed which integrates psychodynamic theory, AA and other 12-step groups, family therapy, and dual-diagnosis issues into a phase specific method. This therapy is done in three stages: (1) dryness (assessment and detoxification); (2) sobriety (achieving stable abstinence); and (3) wellness (using sobriety as a basis for personal growth and intimacy. The utility of an evolving concept of countertransference and new studies demonstrating the efficacy of psychotherapy are also discussed. Several challenging research questions are presented which, if answered, would assess the efficacy of this model. PMID- 2269555 TI - Psychological changes during pulmonary rehabilitation and target-flow inspiratory muscle training in COPD patients with a ventilatory limitation during exercise. AB - The effects of pulmonary rehabilitation (PR), target-flow inspiratory muscle training (IMT) and a combination of both treatments (PR + IMT) on psychological parameters and the physical performance were studied in a group of sixty chronic obstructive pulmonary disease (COPD) patients with a ventilatory limitation during exercise (mean age +/- 59, mean FEV1 +/- 50% of predicted). After the ten week training period scores of anxiety and depression were decreased in the PR and the PR + IMT group, but not in the IMT group. In the PR group these scores were still decreased after a one year follow up period. Maximal workload and the activities in daily life (ADL) scores were improved significantly after the training period in the PR and the PR + IMT group. Most of these improvements had disappeared after one year. The 12 min walking distance was increased in all patient groups after the training period and was still increased after the follow up period. The exercise capacity was correlated significantly to lung function parameters. The psychological well-being, however, was not correlated with lung function parameters, but was closely related to ADL scores. The improvement of the psychological parameters was not correlated to the improvement of the exercise capacity after the training period or after one year. The results indicate that the psychological well-being and the physical condition are improved by different mechanisms during a pulmonary rehabilitation programme. PMID- 2269556 TI - Autism and mental retardation: the planning of a therapeutic environment. AB - Autism and mental retardation are concepts of a different level. The combination of these concepts in the mentally retarded autistic child requires a specific therapeutic environment. This therapeutic environment must take full account of both the child's limited cognitive potentials and the specific needs and limitations on the basis of autism. Such an integrated approach of the mentally retarded autistic child becomes possible when all the symptoms and behaviours of the children are organized in one coherent frame of reference organized according to the main axes of child development (biological, physical, cognitive and socio emotional). The consequences of these partly dissimilar, divergent needs and limitations of mentally retarded autistic children for the planning of a therapeutic environment are discussed. Special attention is paid to the combined effect of mental retardation and autism on the cognitive development axes. PMID- 2269557 TI - Research and practice with congenital amputees: making the whole greater than the sum of its parts. AB - This paper highlights the need for methodologically sound research on the motor, cognitive and psychosocial development of children with congenital limb deficiencies and the integration of findings in these three areas. Such topics have received little attention in the literature and systematic attempts to apply developmental theory to the assessment, fitting, training and evaluation of these children seldom have been made. A number of important current issues in research and practice are critically reviewed including optimal age for fitting, training procedures, prosthesis usage, cognitive deficits and vulnerability to psychosocial problems. Recommendations for the adoption of a more holistic approach to research and practice with amputee children are presented and the need to develop strategies for systematic evaluation and follow up is emphasized. PMID- 2269558 TI - Applicability of the Blind Learning Aptitude Test to Indian children. PMID- 2269559 TI - Reading and writing skills in deaf adolescents. PMID- 2269560 TI - Supported employment for persons with severe and profound mental retardation: a critical analysis. AB - An analysis of the employment outcomes of 109 persons with severe profound mental retardation was undertaken. The mean age of the group was 28 years and mean intelligence quotient (Stanford-Binet) was 30. The data were drawn from over 90 local community programmes in the United States. Results indicated that all persons were in supervised residential situations and that 93% of the total were competitively employed with the mean wage being $3.63 per hour. Mean hours of weekly employment were 22 hours. After 12 months of placement, 81.5% of the clients were still employed. Supported employment has provided new work opportunities for a group of people long reviewed as permanently unemployable. PMID- 2269561 TI - Gluten-free diet and elemental diet in dermatitis herpetiformis. PMID- 2269562 TI - Podophyllin therapy for condyloma acuminatum. PMID- 2269563 TI - Is dermatitis herpetiformis a gluten-sensitive enteropathy? PMID- 2269564 TI - The potency, efficacy, and usage of superpotent topical corticosteroids. PMID- 2269565 TI - Dual publication and manipulation of the editorial process. PMID- 2269566 TI - Keratotic melanocytic nevus. AB - Thirty-five percent of 363 melanocytic nevi were found to have a keratotic epithelial architectural pattern that was mostly infundibular and not previously emphasized. Keratotic melanocytic nevi were commonly from the trunk of women, and most were associated with an intradermal melanocytic nevus. The clinical and histopathologic features as well as a review of the literature of these keratotic melanocytic nevi are presented. PMID- 2269567 TI - Sporotrichosis in Nepal. AB - The first case of sporotrichosis from Nepal is reported in a 25-year-old man from a village about 60 km east of Kathmandu. He never travelled outside of Nepal before and had acquired the lymphocutaneous form of the disease after an accidental injury to the right foot while cutting wood. The diagnosis of the case was made by culturing Sporothrix schenckii from the lesions, proving the dimorphic character of the fungus in vitro, its pathogenicity in mice, and its serology. Oral potassium iodide therapy resulted in complete cure. PMID- 2269568 TI - Bullous pemphigoid with circulating basal cell layer antibodies. PMID- 2269569 TI - Porokeratosis of Mibelli with a dentigerous cyst. PMID- 2269570 TI - Xanthoma disseminatum. PMID- 2269571 TI - Clobetasol propionate ointment 0.05% versus diflorasone diacetate ointment 0.05% in moderate to severe psoriasis. PMID- 2269572 TI - The effect of superficial x-radiation on epidermal Langerhans cells in human skin. PMID- 2269573 TI - Argon laser treatment of small keratoacanthomas in difficult locations. AB - Seventeen patients (mean age, 64.7 years) with solitary keratoacanthomas (KA) located on the face and auricles were treated with the argon laser. All lesions were less than 10 mm in diameter and had been present for 2-10 weeks (mean, 3.8 weeks). The diagnosis was made clinically and was confirmed by histology. The lesions were treated with the argon laser using the continuous exposure technique with a power setting of 4.5 watts (W) and a beam diameter of 1 mm. Complete re epithelialization occurred within 14-21 days. Excellent treatment results were achieved in 65% of the patients. Thirty-five percent healed with mild scarring. During a follow-up period of 2 years no recurrences were noted. The use of the argon laser for removal of small KAs in difficult locations, which would often require invasive surgery, appears to be an effective additional treatment modality. PMID- 2269574 TI - Dapsone in Sweet syndrome. PMID- 2269576 TI - Reflections by a dermatologist in Zimbabwe. PMID- 2269575 TI - Pemphigus herpetiformis. PMID- 2269577 TI - Some dermatoses peculiar to Sikh men. PMID- 2269578 TI - New discoveries in obesity: an introduction to the NAASO 1989 Ethan Sims Young Investigator award. PMID- 2269579 TI - Receptor and postreceptor effects of free fatty acids (FFA) on hepatocyte insulin dynamics. AB - The effects of free fatty acids (FFA) on insulin receptor binding and processing (internalization, degradation, dissociation, and release) were examined in hepatocytes isolated from 12-week-old female rats. Animals were fasted for 24 h to deplete liver glycogen and lipid content. Cells were preincubated for 30 min or 3 h at 37 degrees C in media containing 10 mM lactate, 1 mM pyruvate, and 3.5 percent albumin with increasing concentrations of palmitate (0.00, 0.05, 0.2, 0.5, 1.0 and 2.0 mM). Under these conditions palmitate is the primary substrate for cellular metabolism, and its major fate is oxidation. Equilibrium binding was determined after 18-20 h of incubation at 4 degrees C with radiolabeled insulin and increasing concentrations of unlabeled hormone. With increasing palmitate concentration, a dose-dependent decline in cell-surface insulin receptor binding was observed. Binding decreased by 35 percent and 44 percent after 30 min and 3 h of preincubation with 2 mM palmitate, respectively. This decrease was due to a reduction in insulin receptor number. Receptor-mediated insulin processing was evaluated in cells prelabeled at 4 degrees C with 125I (A14)-monoiodoinsulin at an insulin concentration of 100 pM and reincubated at 37 degrees C for up to 30 min. The amount of internalized insulin was decreased by preincubation of hepatocytes with palmitate. This decrease was proportional to the reduction in cell-surface insulin receptor density at palmitate concentrations of 0.05-0.5 mM, but was disproportionally greater at higher fatty acid concentrations. Receptor mediated insulin degradation decreased at palmitate concentrations between 0.05 and 1.0 mM. At 2 mM, however, insulin degradation was enhanced. This enhancement was observed after 30 min or 3 h of exposure to the fatty acid. Dissociation and/or release of cell-associated internalized insulin was not influenced by the FFA exposure. The effects of FFA on hepatocyte insulin binding and processing were contingent upon cellular metabolism, since no changes were noted when cells were preincubated with palmitate at 4 degrees C under otherwise similar conditions. Thus the in vitro exposure of hepatocytes to FFA influences both receptor and postreceptor events mediating insulin metabolism. These effects may account for the altered hepatic insulin extraction and sensitivity that accompany abdominal obesity and its progression to diabetes. PMID- 2269580 TI - Lactate generation following glucose ingestion: relation to obesity, carbohydrate tolerance and insulin sensitivity. AB - To examine early metabolic abnormalities in obesity prior to the development of carbohydrate intolerance, we studied 14 lean and 37 obese subjects with normal glucose tolerance. All subjects underwent a standard 75 g oral glucose tolerance test (OGTT) with the addition of lactate measurement. As expected, there was a positive relationship between basal insulin and body mass index (BMI kg/m2;r=0.64, P less than 0.0001). In addition, even though the subjects had normal glucose tolerance, both basal glucose and sum of glucose during OGTT showed significant positive associations with obesity. Basal lactate correlated significantly and positively with obesity (r = 0.29, P = 0.04). When incremental areas during OGTT were examined, glucose area during OGTT was positively associated with BMI and insulin area was positively associated with both BMI and sum of glucose. Conversely, the incremental area of lactate decreased as BMI increased (r = -0.41, P = 0.003), despite the increasing glucose area. The results indicate that even prior to frank carbohydrate intolerance, progressive changes in basal levels of glucose, insulin, and lactate, as well as sum of glucose, accompany the expansion of adipose mass in obesity. Two different aspects of lactate metabolism have been examined in obesity. First, the association of increased basal lactate levels with increased obesity may reflect increased lactate production from enlarged adipocytes and an increased fat mass. Secondly, the inverse association between acute lactate generation following glucose ingestion and obesity, despite the increased sum of glucose in obese subjects, may reflect a decreased ability of adipose and/or extra-adipose tissues to convert glucose to lactate due to insulin resistance. PMID- 2269581 TI - Ileal transposition surgery attenuates the increased efficiency of weight gain on a high-fat diet. AB - High-fat diets enhance weight gain in rats and humans. Ileal transposition surgery (IT) causes long-term weight loss on ad libitum food intake. This study was designed to study the effect of high-fat diets on weight loss following ileal transposition surgery. We weight matched 40 rats, performed IT or sham IT, and fed defined high-carbohydrate (12 percent kcal as fat) or high-fat (45 percent kcal as fat) diets for 15 weeks postsurgery (N = 10/group, data are means +/- s.e.m.). Overall, IT rats ate less than sham IT rats, 9587 +/- 304 v. 10,615 +/- 356 kcal (39.6 +/- 1.2 v. 43.8 +/- 1.5 MJ) (P less than 0.01), and gained less weight (-14 +/- 7.8 v. 46 +/- 13.7 g) (P less than 0.01). Sham IT rats had similar food intakes on the two diets, but body weights were increased on the high-fat diet. However, the IT rats on the high-fat diet did not gain more weight or have higher efficiency of weight gain than did the IT rats on the high carbohydrate diet. We conclude that ileal transposition attenuates the increased efficiency of weight gain usually associated with consumption of a high-fat diet. The mechanisms of this decreased metabolic efficiency are unclear. PMID- 2269582 TI - Adipose tissue determinations in cadavers--a comparison between cross-sectional planimetry and computed tomography. AB - The adipose tissue surfaces in 11 slices (+/- 5 cm from the umbilicus) were compared in two cadavers using computed tomography (CT) versus planimetry of band sawed slices of the corresponding sections. A very close correlation was found with partial correlations of around 0.90. Retroperitoneal fat formed a considerable proportion of the total adipose tissue surface in the slices. The results were similar whether fat was defined as -250 to -50, -190 to -30, or -140 to -40 Hounsfield units. These data indicate that CT measurements agree closely with a direct morphometric method and thus can be used as a 'gold standard' for future development. The fact that fat which is located extraperitoneally, but still intraabdominally, constitutes a significant proportion of the slice surface in the umbilical region indicates that data relating intraabdominal fat measurements to metabolic functions must be interpreted with caution. PMID- 2269583 TI - [Jails and AIDS. Risk factors for HIV infection in the prisons of Madrid]. AB - The spread and risk factors for HIV infection were studied in 288 men and 95 women at the prisons of Carabanchel and Yeserias, Madrid. These men and women requested care at the AIDS prevention program in the jails of Madrid, from April to December 1987. Among the men studied at Carabanchel, 55% were positive to HIV (77% seropositivity among intravenous drug users, IVDU). Tattooing (OR = 2.8), and number of times in prison (OR = 4.5 comparing those who had been 8 or more times in prison with those who had been in prison only once) were independent risk factors for infection, after controlling for IVDU. No association was found between seropositive status to HIV and reported anal intercourse. Among the women studied at Yeserias, the proportion of HIV seropositive women was 26% (70% of the IVDUs were seropositive). Tattooing, number of times in prison, history of prostitution and history of syphilis were associated with HIV infection. When controlling for IVDU, number of times in prison and history of prostitution were not independent risk factors for infection. These data indicate that there is a need for control measures to avoid further spread of the HIV infection among the inmate population, in particular through the use of contaminated needles while in prison. PMID- 2269584 TI - [Behavior of mortality indicators in small geographic areas: relative standardized mortality ratio and standardized proportional mortality ratio]. AB - One of the most commonly used indicators in mortality studies is the Standardized Mortality Ratio (SMR) being the Relative Standardized Mortality Ratio (RSMR) an indicator of the relative magnitude of the SMR for a specific cause of death. Along with these indicators, which must be calculated by using the population at risk, there is the Standardized Proportional Mortality Ratio (SPMR), an indicator which measures the excess mortality referring to the proportional mortality established for a standard population. This paper reviews the theoretic conditions described in literature as being necessary to establish a probability interval for the RSMR centered on the SPMR as well as the correlations between both indicators and the use of the SPMR as a predictor of the RSMR. The results obtained clearly show how difficult it is for these theoretic conditions to exist. However, they do suggest that the SPMR be used as a predictor of RSMR. PMID- 2269585 TI - [Attributable risk: its forms, uses and interpretation]. AB - The concept of Attributable Risk, described for the first time more than three decades ago, is rarely used in the analysis and interpretation of epidemiologic studies, despite its interest and importance in methodologic developments of the last years. This paper describes the different forms of Attributable Risk, their applications, and the limitations for their use. The possible reasons that could explain why its use has been set aside by modern academic epidemiology are also discussed. PMID- 2269586 TI - [Perspectives on the application of automated systems to epidemiologic surveillance in Cuba]. AB - A few considerations on the development of the applied automatization of epidemiologic surveillance systems in Cuba are exposed. Reference is made to aspects of the national strategy, to the lines of development of the National Health Systems, to the projections of the subsystems of epidemiologic surveillance, and to the future integrated intercommunication. PMID- 2269587 TI - [Use of a consensus method for determining health needs in Elche]. PMID- 2269588 TI - [Multihospital systems]. PMID- 2269589 TI - [What is the scientific import of estimating the quality of mortality statistics?]. PMID- 2269590 TI - [The perinatal mortality statistics in Spain: must we throw in the towel?]. PMID- 2269591 TI - [The association between alcohol consumption and health services utilization]. AB - The association between alcohol consumption patterns and the use of health services was examined in a cross-sectional survey of the general population of the Region of Madrid. Logistic regression analysis was used to determine the odds of moderate drinkers, excessive drinkers and non-drinkers to utilize health care services. Our findings indicate that moderate drinkers have a lower probability of utilizing health care services as compared to non-drinkers. Specifically, moderate drinkers showed a lower probability of utilizing both hospital (OR = 0.65 CI = 0.48-0.89) and ambulatory care (OR = 0.79 CI = 0.66-0.95) services. Furthermore, the frequency of use of ambulatory (OR = 0.79 CI = 0.64-0.95) and emergency care services (OR = 0.38 CI = 0.21-0.69) was also lower for moderate drinkers. Excessive drinkers also showed a tendency to use emergency care services less frequently (OR = 0.43 CI = 0.19-0.93). Both moderate and excessive drinking were also significantly associated with a shorter length of stay as compared to non-drinkers. The odds ratios are 0.41 (CI = 0.21-0.79) and 0.29 (CI = 0.19-0.39) respectively. Possible explanations of this "protective" effect of alcohol consumption, especially of moderate drinking, are discussed in relation to the diagnostic entities motivating the use of health care services. PMID- 2269592 TI - Local pattern electroretinograms and ganglion cell activity in the turtle eye. AB - 1. Local electroretinograms and spike activity from ganglion cells were recorded from an eye cup preparation of the turtle retina. The responses were elicited with striped and plaid stimulus patterns. 2. The results obtained with the two forms of recording were highly similar. Both depended on the spatial phase of the pattern with respect to the recording electrode. Both had maximal response at the same stimulus spatial frequency. 3. The optimum spatial frequency (both for maximum electroretinogram amplitudes and spike discharge rates) shifted to lower values with the administration of the GABA antagonist, picrotoxin. 4. The low frequency falloff associated with this spatial tuning may point to a mechanism of lateral interactions common to the local electroretinogram and spike responses. PMID- 2269593 TI - Does hair zinc predict amphetamine improvement of ADD/hyperactivity? AB - In 18 boys with ADHD (ages 6-12) in a balanced crossover design, parent and teacher hyperactivity rating differences between one month of dextroamphetamine and one month of placebo correlated significantly (p less than .05, 2 tailed) on Pearson's r with baseline hair zinc levels and nonsignificantly with 24-hour urinary zinc excretion. The signs of the correlations were such that a higher baseline zinc predicted a better placebo-controlled response to amphetamine. Patient baseline urinary zinc was significantly (p less than .02) lower than 7 normal controls. These findings are compatible with the possibility that some ADHD children may be mildly deficient in zinc and constitute poorer stimulant responders. Correlations of zinc levels with 24-hour urinary MHPG were in the expected direction but nonsignificantly by 2-tailed test. PMID- 2269594 TI - Contrast and hemispheric asymmetry: an electrophysiological investigation. AB - Visual evoked potentials by 8 Hz phase-reversed sinusoidal gratings of different spatial frequency were recorded from occipital and temporal leads of left and right hemispheres. Seven adult subjects were investigated. At low contrast, the VEP amplitudes in the two hemispheres were symmetrical. At medium and high contrast, the amplitudes were larger in one hemisphere. On the contrary, the "phase advance" as a function of contrast was comparable in the two hemispheres. The results were discussed according to the literature on different neural population involved in contrast perception. PMID- 2269595 TI - Temporal coherence of superimposed EEG waves: a problem in nonlinearity. AB - Traditional "stimulus-time-locked signal averaging" of human EEG, as usually practiced in both clinical and basic contexts, assumes the superposition principle of algebraic summation for a linear time series. But there are now experimental data on nonlinear coupling of neural populations in the brains of two species, and reasons for regarding human EEG as a nonlinear, chaotic time series, reflecting a global mixture of subharmonics and harmonics of continually varying "fundamental" frequencies within the commonly observed power spectrum of a subject attending to sensory input (about 3-35 Hz). So we must ask ourselves if the established conventions for averaging and temporal comparison of both scalp conducted voltages and related magnetic fluxes from human heads are appropriate for the suspected nonlinear coupling of neural oscillators. PMID- 2269596 TI - Long-latency evoked potentials during aura of temporal lobe origin. AB - Long-latency evoked potentials recorded from scalp or scalp/sphenoidal electrodes have been shown to have diminished amplitude and power during interictal recordings on the side ipsilateral to an unilateral mesial temporal lobe (MTL) focus. We now report recordings of long-latency evoked potentials both during a prolonged aura and also on two seizure-free days. P3 amplitude and sphenoidal evoked potential (SpEP) spectral power in the scalp/sphenoidal channels were less, ipsilateral to the MTL focus. During the aura, the SpEPs had reduced power and reduced amplitude. However, the amplitude of the N2 component for the target averages in the CZ-A1A2 channel was markedly enhanced during the aura. PMID- 2269597 TI - Serial dependency in the discharge pattern of dorsal spinocerebellar tract neurons: a computer simulation analysis. AB - We have developed a model in order to analyze the factors eventually responsible for the strong negative serial dependency between successive interspike intervals in the discharge of the Dorsal Spinocerebellar Tract (DSCT) neurons. This dependency is reflected, phenomenologically, by short intervals followed by long ones and, quantitatively, by the first order correlation coefficient (R1-2); which can be lower than -.6 (Jansen, Nicolaysen & Rudjord, 1966; Kroller and Grusser, 1982). We have found that the lowest values of R1-2 are always related with model parameter values which were very similar to those obtained experimentally. It was observed that EPSP amplitude distribution plays an important role in the discharge patterns of the DSCT neurons. There is one fiber that elicits EPSPs greater than 6 mV, which is responsible for the genesis of the short intervals in the discharge. Long intervals are determined basically by a suprathreshold depolarization and the afterhyperpolarization processes. PMID- 2269598 TI - Toward a model to explain infant preferences by cerebral emotional asymmetry and hemisphere priming. AB - This paper argues that the rightward preference observed in most infants can be described as the consequence of two characteristics of the human brain: (1) hemispheric asymmetry of processes underlying emotional experience and (2) priming of cerebral function. Ample research evidence supports each of these propositions, and they have gained increasing, though not universal, acceptance. In combination, they provide a sufficient explanation for several preferences which may have human survival value. They also produce several side-effects in human behavior which can be observed, but which appear to have no survival function. PMID- 2269599 TI - Pineal melatonin functions: possible relevance to Parkinson's disease. AB - Barbeau hypothesized that Parkinson's disease is associated with hypothalamic deficiency of the specialized neuroendocrine cell system (A.P.U.D.) and that the degeneration of brainstem monoaminergic neurons is secondary to progressive functional loss of this cell system in the disease. The pineal gland meets criteria of the A.P.U.D. cell system and it is possible that dysfunction of the pineal gland may be associated with the pathophysiology and clinical manifestations of Parkinson's disease. Since the role of pineal melatonin in humans remains enigamatic, it is currently unclear which of the symptoms of Parkinson's disease may be associated with deregulation of the secretory activity of pineal melatonin. This review summarizes evidence linking possible alterations of pineal melatonin functions with the clinical manifestations of Parkinson's disease. PMID- 2269600 TI - Lateralized interference in concurrent manual activity: influence of age in children. AB - Thirty-six right-handed bilingual children equally drawn from the two age groups of seven to nine, and eleven to thirteen years, concurrently performed a sequential finger tapping task while: (a) sitting quiet (b) reading aloud, and (c) reading aloud with an instructions to read carefully. The results showed that reading interfered more with right- than with left-hand tapping, but only in older children. The careful reading condition, however, did not add any further manual interference. The data suggest that differential right-hand tapping disruption varies with age and/or with the amount of exposure to a language or languages. These results are discussed in terms of variant and invariant cerebral asymmetry of function during childhood. PMID- 2269601 TI - The differential hemispheric processing of emotion: a comparative analysis in strongly-lateralized sinistrals and dextrals. AB - The neural processing of emotion and the differential processing of affect and cognition are thus far poorly understood. Complex results across studies suggest involvement of the left hemisphere, the right hemisphere, or both. Since handedness is related to cerebral dominance, the present study undertook a comparative analysis of neural processing in strongly lateralized left- and right handed populations. Parietal EEG and bilateral electrodermal activity were recorded while carefully selected subjects were exposed to emotional stimuli under cognitive, affective, and neutral conditions. Results showed greater lateral differentiation and differentially greater left-hemisphere activation in dextrals but greater overall activation in sinistrals. These findings are consistent with the common observation that cerebral organization is more diffuse in left-handed populations. It seems clear that the comparative study of sinistrals and dextrals can help us to better understand how emotion is processed in the brain. PMID- 2269602 TI - The relationship between the pediatric neurological examination and neuropsychological assessment measures for young children. AB - Children with some degree of neurological dysfunction have traditionally been assessed by means of pediatric neurological examinations and/or neuropsychological test batteries. The present study investigated the relationship between these two different assessment methods in a normal population of 129 kindergarten and second grade students. Results indicated that of the 396 correlations conducted for each grade, 18% of the kindergarten and 15% of the second grade sample correlations were significant at the .01 level. Given the relatively few positive correlations, and the fact that there were few consistent patterns within and across grade levels, it was concluded that these two assessment procedures measure different areas of functioning and constitute two separate components of a broad evaluation of the relationship between behavior and the adequacy of brain functions. PMID- 2269603 TI - Mechanisms of action of ECT in Parkinson's disease: possible role of pineal melatonin. AB - Recent clinical studies have suggested that electroconvulsive therapy (ECT) may be efficacious in the therapy of Parkinson's disease (PD). However, the mechanisms of action of ECT in PD are largely unknown. PD may be associated with reduction in the secretory activity of pineal melatonin, and the therapeutic efficacy of ECT in PD may be associated with an effect on the secretory activity of pineal melatonin. Further studies involving analysis of plasma melatonin levels and circadian release prior to and following ECT are needed more precisely to determine the role of pineal melatonin in PD and in the therapeutic efficacy of ETC in PD. PMID- 2269604 TI - Sex differences in neuropsychological performance for children with reading deficits. AB - This study examined sex differences in neuropsychological functioning for a large sample of public school children with reading deficits. Specifically, scores on the Weschsler Intelligence Scale for Children--Revised (Wechsler, 1974), the Halstead-Reitan Neuropsychological Battery for older children (Reitan, 1969) and the Wide Range Achievement Test (Jastak and Jastak, 1978) were compared for males and females in a multivariate fashion. Significant sex differences were found in motor, verbal and nonverbal functioning. Females seemed to be more aberrant than males in expected neuropsychological performance. PMID- 2269605 TI - Neurobiological background of pain and analgesia: the attempt at revaluation according to position of the organism's adaptive activity. AB - The most adequate and successful way to understand the essence of any complex psychophysiological phenomenon, including pain, is obviously the study of its origin, its genesis, i.e., its biological background. Based on critical analysis of recent literature and our own electrophysiological, biochemical and pharmacological data we tried to overcome the difficulties and contradictions derived from the traditional reflex approach and analytical orientation in understanding the experimental investigation of pain-related problems and to determine the neurobiological background of pain and analgesia through the notion of the organism's adaptive activity. Interrelations between the notion of pain and other biological and psychological ideas, the place and functional significance of pain and endogenous analgesic mechanisms in the organization, maintenance and regulation of the organism's adaptive activity, characterization of the involvement of endogenous opioid peptides and monoamines in central processes associated with pain and analgesia, the essence and mechanisms of pain depressing activity of the opiates are the main stages in our neurobiological consideration of the phenomenon of pain and its natural and pharmacological regulation. PMID- 2269606 TI - Age-related change in P3 amplitude as a function of predictable and unpredictable rare events. AB - The auditory event-related potentials (ERP's) of young, middle-aged and elderly subjects were measured over Fz, Pz, C3 and C4 in two different rare tone conditions. In the fixed condition, the rare tone occurred predictably, every fourth stimulus. In the random condition, the rare tone was presented unpredictably, with 1:4 probability. Large amplitude late positive waves (P3's) of middle aged subjects (N = 22) were present in the random condition at all placements, but absent in the fixed condition. Elderly subjects (N = 23) responded identically to both rare tone conditions at all placements. Young subjects (N = 7) had large amplitude P3 responses to both random and fixed conditions at all placements except Pz. Over Pz, young subjects had patterns similar to middle-aged subjects, with large P3's to the random rare tone but not the fixed rare tone. Elderly subjects may not differentiate the two conditions, either because they have less efficient memory, or because they primarily attend to the global probability of rare tone occurrence. The results with young subjects suggest that recent memory processes involved in discriminating rare tone conditions initially develop over the posterior (Pz) areas. PMID- 2269607 TI - The cerebral hemispheres and bilateral neural nets. AB - A high-level cognitive dichotomy ("language and context") is reviewed in relation to empirical findings concerning the functions of the human cerebral hemispheres. We argue that the right hemisphere's involvement in the generation of connotative and contextual information in parallel with the denotative and literal language functions of the left hemisphere provides an important insight into the organization of viable cognitive systems. The role of the corpus callosum in producing the dichotomy is discussed. Finally, the generation of asymmetrical activity in structurally symmetrical, bilateral neural nets is described. The model demonstrates how complementary memory states can be generated in bilateral nets without assuming different modes of information processing, provided that the nets have inhibitory, homotopic connections. Unlike excitatory connections, inhibitory connections are sufficient to generate asymmetric hemispheric activity without postulating intrinsic differences between the cerebral hemispheres. PMID- 2269608 TI - Relation of hand performance and preference in male and female left-handers to familial sinistrality and writing hand. AB - The relations of hand performance to the degree of left-hand preference, and left minus right-hand performance were studied in left-handed male and female subjects considering familial sinistrality and writing hand. Hand performance was assessed by a dot-filling test; hand preference was assessed by the Edinburgh Handedness Inventory. It was established that there were fundamental differences in relationships between performance and preference measures to sex, familial sinistrality, and writing hand, which also created different patterns in the relationships between hand performance and the difference in performance between hands. PMID- 2269609 TI - Pyridoxine improves drug-induced parkinsonism and psychosis in a schizophrenic patient. AB - Drug-induced Parkinsonism is a common serious side-effect of neuroleptic therapy. In cases of irreversible drug-induced Parkinsonism, pharmacological management is notoriously difficult. A schizophrenic patient with severe neuroleptic-induced Parkinsonism and Tardive Dyskinesia is presented in whom administration of pyridoxine (vitamin B6) (100 mg/d) resulted in dramatic and persistent attenuation of the movement disorders as well as reduction of psychotic behavior. Since pyridoxine deficiency is associated with marked reduction of cerebral serotonin concentrations and pineal melatonin production in rats, the effects of pyridoxine on the movement disorder and psychosis may have been mediated largely by enhancing serotonin and melatonin functions. An additional effect of excess pyridoxine administration on GABA and dopamine activity cannot be excluded. Pyridoxine has been reported to attenuate the severity of levodopa-induced dyskinesias in patients with Parkinson's disease and it is suggested that pyridoxine supplementation should be considered in psychiatric patients with drug induced movement disorders including persistent Parkinsonism. An underlying pyridoxine deficiency in these patients may exacerbate the psychotic behavior and additionally, potentially increase the risk of drug-induced movement disorders. PMID- 2269610 TI - Tardive dyskinesia in bipolar disorders: possible role of pineal melatonin. AB - Several clinical studies have suggested that patients with affective disorders, are at high risk for developing tardive dyskinesia (TD). An intriguing aspect of the relationship between TD and affective disorders involves mood dependent alterations in severity of TD. In most reported cases, depressive episodes are associated with exacerbation of TD, while manic episodes are accompanied by attenuation of TD. Current neurochemical hypotheses of TD do not explain adequately the relations of TD to depression or the mood dependent variations in the severity of TD. I propose that alterations in the secretory activity of pineal melatonin during manic and depressive episodes may explain better both the higher risk of TD in patients with affective disorders and the mood-dependent fluctuations in severity of TD. Consideration of pineal melatonin functions may further our understanding of the pathophysiology of TD in patients with affective disorders. PMID- 2269611 TI - Zinc deficiency in attention-deficit hyperactivity disorder. PMID- 2269612 TI - Early versus late-onset Parkinson's disease: the role of the locus coeruleus. PMID- 2269613 TI - Naloxone analgesia: further developments. PMID- 2269614 TI - Minamata disease: what is a keystone of its molecular mechanism? A biochemical theory on the nature of methyl mercury neurotoxicity. PMID- 2269615 TI - OB care shortage in 28 counties, say survey respondents. AB - For the past several years, the IMS has been receiving reports of shortages of obstetrical services in various Iowa locations. An IMS survey of Iowa physicians yielded some telling results. PMID- 2269616 TI - Traumatic head and spinal cord injury in Iowa. PMID- 2269617 TI - Moss nasogastric tube and treatment of a perforated esophagus. AB - Nonoperative treatment of perforation of the esophagus can have a successful outcome. In conjunction with other modalities, the Moss nasogastric tube most closely simulates benefits obtained by direct surgical intervention upon the perforated esophagus. PMID- 2269619 TI - Radon in Iowa. PMID- 2269618 TI - Documentation is crucial. PMID- 2269620 TI - Blueprint for reform. PMID- 2269621 TI - [Organ preserving surgery in kidney tumors]. AB - Between 1967 and 1989 102 patients underwent conservative surgery for renal tumors at the Department of Urology, Mainz Medical School. In 39 patients the indication for organ preserving surgery was imperative because of single kidney, bilateral tumors, benign pathology of the contralateral kidney or chronic renal failure. In the elective group 63 patients underwent tumor enucleation for small, peripheral lesions of uncertain dignity. Tumors removed for imperative indications varied in diameter from 2-11 cm (mean 5.5 cm) whereas those which were electively resected ranged from 1-7 cm (mean 3.2 cm). 74% of the electively enucleated tumors were detected in an early asymptomatic stage by routine ultrasound investigations. 58 of the 63 patients with elective indications are alive with no evidence of tumor after a mean follow-up of 35 months (5-90 months). One patient was lost to follow-up, 3 patients died of reasons unrelated to cancer, and only 1 patient died of progressive disease. These results indicate, that tumor enucleation is a safe and reliable technique in small, peripheral renal tumors and offers an adequate alternative to radical nephrectomy in selected patients. PMID- 2269622 TI - [Sonography in sinus renalis]. AB - The renal sinus (s.r.) of the kidney is an anatomical entity and well correlated with the central echo-band in the nephrosonogram. For the evaluation of this compartment sonography may be the best practicable method. It's important, however, to differentiate between anatomical variations and real pathological findings to avoid diagnostic errors and waste of other procedures. Diverse appearances are demonstrated and discussed. PMID- 2269623 TI - [Results following radiotherapy for hypernephroma]. AB - From 114 patients treated with local radiotherapy after nephrectomy up to now 46 patients are alive. 59 patients died; 55 patients died because of the tumor, 4 patients died because of other genesis. At 4 patients, who are alive, a secondary therapy because of pulmonary metastasis was performed. Three times a solitary metastasis of the lung was removed surgically. One female patient came into a CR under therapy with Gestagen (Depo Provera). Three patients (2.6%) died because of a local recidive. There was no change of survival rates and local recidive rates compared to surgery alone. PMID- 2269624 TI - [Mobile extracorporeal piezoelectric lithotripsy (EPL)--suitable for which stones?]. AB - We report our experience with the first 42 patients treated with extracorporeal piezoelectric shock wave lithotripsy (mobile Wolf Piezolith 2300, being once a month to our disposition). In our opinion, this fact influences the indication for the treatment with this lithotriptor; large stones should be treated first either by percutaneous litholapaxy or ESWL, with a Dornier-Lithotriptor. PMID- 2269625 TI - [Long-term results of the Cobb and Badge method of bladder neck suspension in the treatment of urinary stress incontinence in women]. AB - According to their authors, surgical techniques proposed to correct female stress incontinence give excellent short-term results. But there is no long-term evaluation and it is generally agreed that half of these patients will be incontinent again several years later. This study evaluates long-term results of the COBB and RADGE bladder neck suspension performed on 47 female patients. At five years 49% of patients are still continent or have improved. If this surgical technique gives no better results compared to others, it has the advantage of being simple and quickly executed. PMID- 2269626 TI - ["Imperative indication" for organ-preserving kidney tumor surgery]. AB - Imperative indications for organ-sparing surgery of renal tumors are given mainly in existing or imminent restriction of renal function. Organ-sparing excision of renal tumors under in-situ protection with HTK-solution compared with operations without protection have the following advantages: 1. reduced blood loss, 2. longer ischemia, 3. better tissue differentiation with benefit for radicality, 4. shorter hospital stay. PMID- 2269627 TI - [Renal tumors in the elderly patient: therapeutic dilemma]. AB - We present a retrospective study of 17 elderly patients (older than 75 years) suffering from renal carcinoma, Robson I to III. 12 patients underwent surgical treatment (radical nephrectomy). Peroperative morbidity was low (10%), mean hospitalisation period was 12 days. 60% of patients returned home directly. Mean survival was 5 years. In the 8 patients group with Robson stage I-II, only one death was due to tumor progression. 5 patients underwent a conservative approach (no treatment at all). In this group, two deaths were due to tumor progression. The difference in outcome of these two groups shows a significant advantage for a surgical approach, even in the elderly. PMID- 2269628 TI - [Endoscopic sphincterotomy in paraplegic patients: retrospective cases in Geneva]. AB - We present a review of 59 spinal cord injury patients with spastic sphincter, treated by external sphincterotomy. Bladder voiding is substantially improved with either twelve o'clock or lateral sphincterotomy. Immediate complications are infrequent. 19% of patients need a second intervention. 78% of patients obtain satisfactory long-term results. Conversely, 12% of patients fail to respond and need an indwelling bladder catheter. Those failures are most likely to be found in patients presenting an impaired detrusor function (40%). 72% of patients have erections before treatment. Among them, 10% report erection loss after sphincterotomy. Fibrosis is present in 71% of sphincter resection piece histologies and appears early in the evolution of the affection. This condition is thought to contribute notably to the formation of a fixed sphincteric obstacle. PMID- 2269629 TI - [NMR tomography of vena cava thrombi: clinical significance in the differential diagnosis and therapy]. AB - 31 patients with advanced renal cell carcinoma underwent abdominal MRI which were examined by an independent experienced radiologist and compared with the intraoperative findings. 12 of 13 vena caval tumor thrombi were diagnosed correctly, 1 small tumor thrombus in a case with large retroperitoneal lymph nodes compressing the vena cava could not be detected. The extension of the tumor in the vena cava could exactly be described in topographic relation to liver, diaphragm and right atrium which is important for planning the operative procedure. PMID- 2269630 TI - [The value of magnetic resonance tomography in the diagnosis of renal space occupying lesions]. AB - 41 patients (45 renal tumours) were examined by magnetic resonance imaging to assess the value of the method and its use to specify renal tumours. Histological findings were available in 38 cases. The results of MRI were compared with the CT and ultrasound diagnosis and the histological findings. In 92.1% (35/38) the CT diagnosis agree with the histological findings, the ultrasound in 76.3% (29/38) and the MRI in 84.2% (32/38). To specify renal tumours the diagnosis by CT-scan and ultrasound is sufficient. PMID- 2269632 TI - [Diagnostic tumor resection in kidney tumors of unclear quality]. AB - From 1985 to June 1989 diagnostic tumour resections have been performed on 37 kidney tumours with unknown dignity following the preoperative imaging techniques. The kidney tumours were completely excised with about 1 cm of adjacent parenchyma outside the pseudocapsule during temporary ischemia. The tumours and biopsies from the resection margins were sent to quick frozen section. In case of benign histology or low grade clear cell carcinomas with exophytic growth and a size of less than 5 cm in diameter the operation was finished without removing of the kidney. In 21 patients with benign and 11/16 with malignant disease the kidneys could be preserved. In 5/16 patients the kidneys were removed after tumour resection and result of the quick frozen section. In our opinion the diagnostic kidney tumour resection in cases of kidney tumours with unknown dignity should be preferred to fine needle biopsies combining diagnostic and therapeutic proceeding in selected cases. On the other hand tumour resections without nephrectomy in patients with renal cell carcinoma and normal contralateral kidney should be done only in low grade tumours of small size. PMID- 2269631 TI - [The treatment of retroperitoneal fibrosis. Report of personal experience with 17 cases]. AB - Between 1974 and 1988 17 patients with retroperitoneal fibrosis were seen in our hospital. 9 patients received medical and surgical treatment: first ureterolysis with intraperitoneal displacement following an immunosuppressive therapy. 6 patients received only immunosuppressive therapy. 1 patient only received surgical treatment. 1 patient showed spontaneous remission. The results of our study confirm that the combined surgical and medical treatment is a good therapy of retroperitoneal fibrosis. An effective treatment with immunosuppressive drug therapy alone is possible in well-chosen patients. PMID- 2269633 TI - [Prognosis and therapy of kidney carcinoma in a retrospective study in 624 patients]. AB - 624 patients, who were treated for carcinoma of the kidney between 1966 and 1987 were analysed in a retrospective study. Prognosis depended in tumor size, lymphatic metastases, and tumor grading. Tumor spread into the renal veins or into the vena cava without lymphatic metastases did not reduce life expectancy. Different symptoms are important as prognostic criteria. Small tumors without spread into the veins can be sufficiently operated from a lumbo costal incision. Preoperative radiation is no beneficial. PMID- 2269634 TI - [Does extracorporeal shock wave lithotripsy injure the female reproductive tract?]. AB - Female reproductive tract lies near the distal ureter where extracorporeal shock wave lithotripsy (ESWL) of calculi is performed. The question whether ESWL may induce morphological changes in ovary, tube or uterus should be investigated in animal experiments. The female reproductive system of 28 Wistar rats was exposed to 600 or 1200 shock waves. After 24 hours or 35 days the animals were sacrificed and examined by light microscopy and scanning electron microscopy (SEM). Acute after ESWL 2/14 rats revealed minimal subcapsular bleeding in the ovaries. SEM showed a desquamation of superficial cells and a loss in microvilli. In long-term groups there was no morphological lesion. Besides the correlation between healthy and atretic follicles were unchanged. In animal experiment no sign of long lasting changes in female reproductive tract after ESWL could be observed. PMID- 2269635 TI - [What is the benefit of systematic regional lymph node dissection in tumor nephrectomy?]. AB - What is the benefit of an extended dissection of the regional lymph nodes in the treatment of renal cell carcinoma (RCC)? We evaluated the results of 511 consecutive patients which we operated on RCC. The data of 320 patients (SLD) who had an extended dissection of the regional lymph nodes have been compared with those of 191 patients (FLD) who had a dissection of none or only of a few nodes for staging reasons. All patients were nephrectomized under curative intent (M0) with a transabdominal approach. 1. The incidence of N+ in the SLD group was 17.5% and 10% in the FLD group. 2. The overall 5-year survival rates were 58% after FLD and 66% after SLD, the 10-year survival rates 38% after FLD and 54% after SLD (p less than 0.01). 3. The perioperative mortality of patients with extended dissection was 0.9%. We conclude from our data that the extended dissection of the regional lymph nodes significantly improves the prognosis of patients which were operated for RCC. PMID- 2269636 TI - [Study of large cross sections of infiltrating renal cell carcinoma (pT3) and long-term observation (more than 4 years)]. AB - In a series of 59 consecutive renal cell carcinomas (pT3) cross sections were performed and grading was reevaluated on a cytological basis as described by Thoenes. Follow-up was at least 4 years. Only 20.3% of all tumors revealed monoform grading (92 resp. 93), while 79.9% consisted of more than one grading (G1+G2, G2+G3: 45.8%; G1+G2+G3: 33.9%). Prognosis in this series depended highly significantly (p less than 0.002) on the percentage of G3-area of the vital tumor (NED greater than 4 ys.: 11.4%; DOD less than 2 ys.: 51.6%). It is concluded that measuring different G-areas in cross section of renal cell carcinomas raise considerably prognostic value of histopathology. PMID- 2269637 TI - [Organ-preserving therapy in kidney tumors]. AB - Renal cell carcinoma in solitary kidneys or both kidneys requires renal sparing tumour resection to avoid renal failure. This paper presents the course of 16 patients with 17 solid renal tumours. The results achieved with this approach in T1-2 N0 M0 tumours are similar to those of radical nephrectomy. PMID- 2269638 TI - [The value of cavernous body radiography in penile diseases]. AB - Cavernous body radiography is of great importance in the diagnosis of penile disorders. An exact localisation of structural changes of the cavernous bodies is possible and also identification of venous leaks causing erectile dysfunction. PMID- 2269639 TI - ["Mixing" of implants, a basic problem]. AB - The so-called "mixing" of implants and instruments of different producers in hospitals leads to some risks. The use of standardized implant materials (e.g. stainless steel ISO 5832/1) by different producers is necessary but not sufficient for combining an osteosynthesis plate and a bone screw from different sources. The design, the dimensions and tolerances, the manufacturing, the quality control, the well tested applicational technique can be different too for the implants and the necessary instruments as well. This may lead to damage, failure or fracture of the biomechanical system called "osteosynthesis", that means failure of the therapy. Finally the patient pays for the problems. Some examples illustrate the potential problems for the involved staff or institutions. The use of a unique consistent well tested and approved set of implants and instruments must be recommended strongly to avoid any additional risk. PMID- 2269640 TI - [Surgical treatment of metapneumonic pleural empyema]. AB - During a period of 13 years 54 patients have been treated for metapneumonic pleural empyema, namely 3 children (all boys), 31 men and 20 women. One patient was admitted in extremis heavily intoxicated after unsuccessful attempt at closed drainage. He died during thoracotomy for open drainage. All the remaining 53 patients were cured, 3 out of 18 by closed thoracostomy (Bulau), 12 out of 16 by open drainage and 37 by decortication which had to be combined with pulmonary resection 13 times. Local treatment of pleural empyema is aimed at the obliteration of the pleural space. This goal can best be accomplished: in the acute exudative stage of the disease (according to the American Thoracic Society) by closed thoracotomy, in the fibrino-purulent phase by open thoracotomy with rib resection and in the chronic organizing stage by decortication. PMID- 2269641 TI - [Autologous epithelium transplantation using cultured keratinocytes. History and current role in burn treatment]. AB - The history and practical aspects of skin replacement by cultured autologous epidermal cells is discussed. We present the technical methods of keratinocyte culture and grafting as well as the clinical applications especially in burn patients. PMID- 2269642 TI - Individual differences in autonomic learning: a quarter century of reflection. AB - A series of studies carried out over the past two decades has shown selected group differences in the speed and final level of learned control of various autonomic functions. The Pavlovian and operant conditioning of as many as 6 physiological variables have revealed varying ability for this form of control. Studies were performed on subject populations that included drug-free chronic schizophrenics and healthy controls, psychopathic and non-psychopathic male juvenile delinquents, and a clinical population that included migraine sufferers and persons undergoing psychotherapy. Also studied were school dropouts in vocational training, inner-city high school seniors and junior high school students at a university school. These studies carried out on normal and abnormal individuals of strikingly different social backgrounds have lent consistent support for the hypothesis that an aptitude for autonomic learning is basic to social motivation, achievement, emotional control, and empathy. PMID- 2269643 TI - Cerebral lateralization for language revealed in neuronal responses of the human brain cortex. AB - Neuronal impulse activity (NIA) of the cortex and subcortical nuclei in the thalamus and striopallidar complex was studied during performance of the word recognition test in patients with long-term intracerebral electrodes implanted for diagnostics and therapy. In NIA of the left hemisphere cortex, endogenous responses were found to prevail in the interval between expositions of two stimuli, whereas NIA of the right cortex exhibited more responses during perception of stimuli. Asymmetry in neuronal responses of subcortical nuclei in the thalamus and striopallidar complex appeared to differ from that observed in the cerebral cortex. PMID- 2269644 TI - Event-related perturbations in an electrophysiological measure of auditory sensitivity: effects of probability, intensity and repeated sessions. AB - It is often held that novel or salient stimuli are followed by a brief period of orienting or alerting during which sensory processes are facilitated. Evidence for such a period of facilitation was sought in a paradigm in which evoked responses to weak auditory probe stimuli were examined when given in the presence of salient foreground stimuli, which were varied in probability and intensity, and which were given in two replicate sessions. The background probe stimuli consisted of a continuous train of auditory pip stimuli delivered at a rate of 40 pips per second. Under such conditions of repetitive stimulation a steady-state rhythm (SSR), which is believed to reflect summated early and middle latency evoked responses, is established in the EEG at a corresponding frequency of 40 Hz. The 40 Hz SSR was extracted using a digital averaging and filtering technique and examined continuously for changes in amplitude and latency. The rhythm showed a brief episode during which the latencies of response were decreased. The reduction in latency was greatest at 186 ms after the foreground stimulus, at which time the latencies of individual peaks in the rhythm were reduced by about 3.5 ms. The magnitude of the latency reduction response was larger for intense and for rare stimuli, and showed long-term decrement during the second session. Event-related potential and heart rate responses to the foreground stimulus were also affected by probability, intensity and session, but not in the same pattern. It was hypothesized that the latency shift in the 40 Hz SSR reflects a brief period of sensitization during alerting or orienting responses. PMID- 2269645 TI - Amplitude variations in P300 component due to unpredictable stepwise change of stimulus probability. AB - The present study investigates whether the amplitude of the P300 in 'normal' subjects adapts to unexpected changes in global stimulus probability. The adaptation level (AL) metrics (in terms of Helson's [1964] theory) was applied to explain the variations in the P300 amplitude. In an oddball paradigm the probability of the deviant tone (target 1000 Hz, 80 dB, 50 ms) occurring randomly in a train of standard ones (non-target 1100 Hz, 80 dB, 50 ms) was changed in a stepwise way from 0.5 to 0.3 and then to 0.1 in 3 blocks without interruption of the stimulus presentation. Two experiments were performed. In the first one the subjects did not receive any prior information about the changes in the stimulus probability, whereas in the second experiment they were aware of such changes. The task always required the subject to silently count the deviants. EEG was recorded monopolarly from Fz, Cz and Pz in a total of 15 subjects. The block averaged P300 increased monotonically with probability, the increase being larger in Expt. II. In contrast to the block averaged P300, the variations in the P300 amplitude following the abrupt change in probability showed a non-linear dependency. On the basis of the AL a simulation of the time course of the P300 variations with probability was performed and a clear similarity between the simulated P300 and the experimental data was found. Some properties of the AL model are discussed. PMID- 2269646 TI - Achievement motivation, performance and cardiovascular activity. AB - Cardiovascular measures were obtained from 40 subjects differing in level of achievement motivation during the performance of a vigilance task. Analysis of interbeat interval and heart rate variability indicated that cardiovascular measures obtained from low achievers did not differ significantly from pre-test measures during the performance of the task, while the measures from high achievers did. In addition, the performance of high achievers was significantly better than the performance of low achievers. It is suggested that these findings indicate that high achievers are marked by the effort they expend in performance and that such effort is reflected in the cardiovascular activity of such subjects. PMID- 2269647 TI - An experimental test of the muscle tension hypothesis of tension-type headache. AB - The present study employed an experimental design to provide a direct test of the classic etiological account of tension-type headaches, that these stem from elevated levels of muscle tension. Twenty-eight female subjects with relatively frequent headaches were divided into 4 groups, according to a 2 x 2 design. The independent variables were (1) Target response (to maintain elevated levels of either frontalis EMG or digital temperature for 40 min), and (2) Expectation (either specifically of a headache or of some unspecified discomfort). Dependent variables included headache as well as a number of other possible symptoms. Results showed that subjects were successful in complying with their assigned tasks. However, there were no main effects of Target response or Expectation and no interactions of these factors with respect to headache or any other symptom. These data provide strong evidence against the classic etiological account of muscle-contraction headaches. PMID- 2269648 TI - Development of an ability to maintain verbally instructed central gaze fixation studied in 8- to 10-year-old children. AB - Development of an ability to maintain verbally instructed central gaze fixation was studied in 8-, 9- and 10-year-old boys. The stability of central gaze fixation was tested by the sudden appearance of a novel, peripheral stimulus triggering reflexive saccade. In Experiment I, the ability to maintain verbally instructed central gaze fixation upon nonsense geometrical pattern was found to be equal in 8 and 9 years of life. This ability increased markedly between 9 and 10 years of age. Gaze fixation upon gradually appearing shapes during a TV-like game reducing volitional effort of subject was, however, equal in all age groups. Concentration of attention upon central stimulus as reflected by saccade latency (Experiment I) and P3-N3 amplitude of evoked potentials to peripheral flashes (Experiment II) was equal in both tasks in 8-year-olds. In contrast, higher concentration of attention upon meaningful central stimulus presented during the TV-like game was found in 9- as well as in 10-year-old boys. Developmental changes of the ability to maintain verbally instructed central gaze fixation might be related to the late structural maturation of frontal cortex. PMID- 2269649 TI - Relaxation training combined with increased physical activity lowers the psychophysiological activation in community-home boys. AB - Resting electrical activity (EMG) in the frontalis, temporalis, trapezius and erector trunci muscles, as well as systolic and diastolic blood pressure (BP), were measured in boys in a community home, and in controls of the same age in an ordinary school. EMG in the community-home boys was significantly higher than in controls, whereas BP did not yield any difference. The community-home boys participated in a programme consisting of relaxation training and increased physical activity for 4 months. After this intervention, EMG in all muscle groups was decreased, and the level of EMG was also lower than the values measured in controls. Systolic and diastolic BP in the community-home boys was also lowered, but the decrease was not significant as compared to the control group. In conclusion, relaxation training and/or increased physical activity is effective in decreasing the elevated activation observed in community-home boys. PMID- 2269650 TI - Psychometric properties of non-specific electrodermal response frequency for a sample of male students. AB - In the present study data on the frequency of non-specific electrodermal responses (NSRs) are presented for a large and, with regard to sex, age and educational level, homogeneous sample of male students (n = 590). These data were obtained in 9 independent experiments in which NSRs were recorded under equivalent conditions. NSRs were scored as skin conductance changes greater than 0.02 muSiemens. A recording period of 5 min prior to experimental manipulations was chosen. A systematic comparison between the 9 studies, the distribution of NSRs for the total sample, as well as descriptive data for stabile and labile subgroups are presented. For 213 subjects NSR-frequency was recorded twice, with a retest interval of one day. For these subjects retest analyses and data on the degree of stability of the classification into stabile and labile groups are also presented. In the discussion the necessity to develop standardized scoring criteria for NSRs is emphasized. PMID- 2269651 TI - Characteristics of heart rate fluctuations and respiratory movements during orienting, passive avoidance and flight-fight behaviour in rabbits. AB - In the present study different heart rate patterns were demonstrated to accompany flight-fight behaviour, orienting behaviour and passive avoidance in rabbits. Flight-fight behaviour was characterized by markedly increased heart rate and diminished overall heart rate variability. The effect was mediated by vagal inhibition and beta-adrenergic activation in a type-specific relation. Orienting behaviour was accompanied by a smaller heart rate increase and the exaggeration of slow heart rate fluctuations. The latter effect was absent during beta adrenergic blockade suggesting a behaviourally provoked beta-adrenergic activation. Single beta-adrenergic blockade did not change the characteristics of the heart rate fluctuations at rest. During passive avoidance a vagally mediated heart rate deceleration was followed by a slow heart rate return toward the initial heart rate level. This level was not reached during beta-adrenergic blockade. The enhanced overall heart rate variability during passive avoidance was mainly caused by strengthened respiratory-induced heart rate fluctuations and, furthermore, by exaggerated slow rhythmical heart rate fluctuations. The latter effect was not observed during beta-adrenergic blockade and is referred to as an orienting component within passive avoidance. Three individual behavioural types may be differentiated in rabbits 'Weisses Gross-Silber' by stable behavioural characteristics i.e. spontaneous motor activities, preferred postures at rest and coping behaviour. The results of the present study suggest that different neurovegetative reaction types, i.e. dominating beta-adrenergic or vagal activation are correlated with stable behavioural characteristics, especially in terms of preferring active or passive coping behaviour, respectively. PMID- 2269652 TI - Inferring vagal effects on the heart from changes in cardiac cycle length: implications for cycle time-dependency. AB - Since the now classical experiments by Brown and Eccles in 1934, the effect of a stimulation of the vagus nerve on the heart has been derived from changes in the length of cardiac periods. Based on a simple model for the genesis of heartbeats, it is shown that the procedure employed by Brown and Eccles gives a distorted picture of the actual vagal effect. A corrected procedure for inferring the vagal effect from changes in heart period length is proposed. This new procedure is applied to empirical data from animal experiments with direct stimulation of the vagus nerve. It is shown that, if the vagal effect depends on time of stimulation within the cardiac cycle (cycle time-dependency), single vagal effect curves for each time of stimulation within the cycle have to be constructed. Other data reduction procedures are reviewed with respect to their appropriateness for demonstrating cycle time-dependency. PMID- 2269653 TI - Temporal stability of the hemodynamics of cardiovascular reactivity. AB - Cardiovascular responses to a competitive reaction-time task were monitored in 13 male subjects tested twice, 3 months apart. The temporal stability of blood pressure responses was in line with previous reports. However, in this study impedance cardiography permitted the investigation of the hemodynamic adjustments underlying the observed blood pressure responses. Analyses revealed that cardiac output and total peripheral resistance responses displayed temporal stability, indicating that subjects' blood pressure responses on the two occasions were the result of similar hemodynamic responses. These data thus extend the literature by demonstrating that the hemodynamic response pattern itself represents a stable individual difference variable. PMID- 2269654 TI - Plotting systolic, diastolic, and pulse pressure on a real time scale. AB - Since a valid non-invasive method for continuously measuring blood pressure is available for the psychophysiological laboratory, a procedure must be found for depicting blood pressure characteristics (systolic, diastolic, pulse pressure) on a real time scale, that is not simply from one heartbeat to the next. Values for blood pressure characteristics are actualized by heartbeats and thus occur at discrete points in time only, quite like values for heart rate. It is being assumed that the conditions for the blood pressure characteristics vary continuously, however, and that a value, actualized by a heartbeat, is representative for a time interval extending halfway before and after the point in time where it occurs. For computing a value for a real time interval it is proposed to weight the blood pressure values according to the amount of time their respective time intervals extend within the real time interval. PMID- 2269655 TI - Epidermal differentiation: the bare essentials. PMID- 2269656 TI - Targeting of a cytosolic protein to the nuclear periphery. AB - The yeast nuclear envelope protein NSP1 is located at the nuclear pores and mediates its essential function via the carboxy-terminal domain. The passenger protein, cytosolic dihydrofolate reductase from mouse, was fused to the 220 residue long NSP1 carboxy-terminal domain. When expressed in yeast, this chimeric protein was tightly associated with nuclear structures and was localized at the nuclear periphery very similar to authentic NSP1. Furthermore, the DHFR-C-NSP1 fusion protein was able to complement a yeast mutant lacking a functional NSP1 gene showing that DHFR-C-NSP1 fulfils the same basic function as compared to the endogenous NSP1 protein. These data also show that the NSP1 protein is composed of separate functional moieties: a carboxy-terminal domain that is sufficient to mediate the association with the nuclear periphery and an amino-terminal and middle repetitive domain with an as yet unknown function. It is suggested that heptad repeats found in the NSP1 carboxy-terminal domain, which are similar to those found in intermediate filament proteins, are crucial for mediating the association with the nuclear pores. PMID- 2269657 TI - Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-beta-NGF in vivo. AB - Extracts from BSC-40 cells infected with vaccinia recombinants expressing either the yeast KEX2 prohormone endoprotease or a human structural homologue (fur gene product) contained an elevated level of a membrane-associated endoproteolytic activity that could cleave at pairs of basic amino acids (-LysArg- and -ArgArg-). The fur-directed activity (furin) shared many properties with Kex2p including activity at pH 7.3 and a requirement for calcium. By using antifurin antibodies, immunoblot analysis detected two furin translation products (90 and 96 kD), while immunofluorescence indicated localization to the Golgi apparatus. Coexpression of either Kex2p or furin with the mouse beta-nerve growth factor precursor (pro-beta NGF) resulted in greatly enhanced conversion of the precursor to mature nerve growth factor. Thus, the sequence homology shared by furin and the yeast KEX2 prohormone processing enzyme is reflected by significant functional homology both in vitro and in vivo. PMID- 2269658 TI - Protein retention in yeast rough endoplasmic reticulum: expression and assembly of human ribophorin I. AB - The RER retains a specific subset of ER proteins, many of which have been shown to participate in the translocation of nascent secretory and membrane proteins. The mechanism of retention of RER specific membrane proteins is unknown. To study this phenomenon in yeast, where no RER-specific membrane proteins have yet been identified, we expressed the human RER-specific protein, ribophorin I. In all mammalian cell types examined, ribophorin I has been shown to be restricted to the membrane of the RER. Here we ascertain that yeast cells correctly target, assemble, and retain ribophorin I in their RER. Floatation experiments demonstrated that human ribophorin I, expressed in yeast, was membrane associated. Carbonate (pH = 11) washing and Triton X-114 cloud-point precipitations of yeast microsomes indicated that ribophorin I was integrated into the membrane bilayer. Both chromatography on Con A and digestion with endoglycosidase H were used to prove that ribophorin I was glycosylated once, consistent with its expression in mammalian cells. Proteolysis of microsomal membranes and subsequent immunoblotting showed ribophorin I to have assumed the correct transmembrane topology. Sucrose gradient centrifugation studies found ribophorin I to be included only in fractions containing rough membranes and excluded from smooth ones that, on the basis of the distribution of BiP, included smooth ER. Ribosome removal from rough membranes and subsequent isopycnic centrifugation resulted in a shift in the buoyant density of the ribophorin I containing membranes. Furthermore, the rough and density-shifted fractions were the exclusive location of protein translocation activity. Based on these studies we conclude that sequestration of membrane proteins to rough domains of ER probably occurs in a like manner in yeast and mammalian cells. PMID- 2269659 TI - In vitro reconstitution of intercompartmental protein transport to the yeast vacuole. AB - Toward a detailed understanding of protein sorting in the late secretory pathway, we have reconstituted intercompartmental transfer and proteolytic maturation of a yeast vacuolar protease, carboxypeptidase Y (CPY). This in vitro reconstitution uses permeabilized yeast spheroplasts that are first radiolabeled in vivo under conditions that kinetically trap ER and Golgi apparatus-modified precursor forms of CPY (p1 and p2, respectively). After incubation at 25 degrees C, up to 45% of the p2CPY that is retained in the perforated cells can be proteolytically converted to mature CPY (mCPY). This maturation is specific for p2CPY, requires exogenously added ATP, an ATP regeneration system, and is stimulated by cytosolic protein extracts. The p2CPY processing shows a 5-min lag period and is then linear for 15-60 min, with a sharp temperature optimum of 25-30 degrees C. After hypotonic extraction, the compartments that contain p2 and mCPY show different osmotic stability characteristics as p2 and mCPY can be separated with centrifugation into a pellet and supernatant, respectively. Like CPY maturation in vivo, the observed in vitro reaction is dependent on the PEP4 gene product, proteinase A, which is the principle processing enzyme. After incubation with ATP and cytosol, mCPY was recovered in a vacuole-enriched fraction from perforated spheroplasts using Ficoll step-gradient centrifugation. The p2CPY precursor was not recovered in this fraction indicating that intercompartmental transport to the vacuole takes place. In addition, intracompartmental processing of p2CPY with autoactivated, prevacuolar zymogen pools of proteinase A cannot account for this reconstitution. Stimulation of in vitro processing with energy and cytosol took place efficiently when the expression of PEP4, under control of the GAL1 promoter, was induced then completely repressed before radiolabeling spheroplasts. Finally, reconstitution of p2CPY maturation was not possible with vps mutant perforated cells suggesting that VPS gene product function is necessary for intercompartmental transport to the vacuole in vitro. PMID- 2269660 TI - Transcytosis in MDCK cells: identification of glycoproteins transported bidirectionally between both plasma membrane domains. AB - MDCK cells display fluid-phase transcytosis in both directions across the cell. Transcytosis of cell surface molecules was estimated by electron microscopic analysis of streptavidin-gold-labeled frozen sections of biotinylated cells. Within 3 h, approximately 10% of the surface molecules, biotinylated on the starting membrane domain, were detected on the opposite surface domain irrespective of the direction of transcytosis. This suggests that the transcytosis rates for surface molecules are equal in both directions across the cell as shown previously for fluid-phase markers. A biochemical assay was established to identify transcytosing glycoproteins in MDCKII-RCAr cells, a ricin resistant mutant of MDCK. Due to a galactosylation defect, surface glycoproteins of these cells can be labeled efficiently with [3H]galactose. Transcytosis of [3H]galactose-labeled glycoproteins to the opposite membrane domain was detected by surface biotinylation. Detergent-solubilized glycoproteins derivatized with biotin were adsorbed onto streptavidin-agarose and separated by SDS-PAGE. A subset of the cell surface glycoproteins was shown to undergo transcytosis. Transport of these glycoproteins across the cell was time and temperature dependent. By comparative two-dimensional gel analysis, three classes of glycoproteins were defined. Two groups of glycoproteins were found to be transported unidirectionally by transcytosis, one from the apical to the basolateral surface and another from the basolateral to the apical surface. A third group of glycoproteins which has not been described previously, was found to be transported bidirectionally across the cell. PMID- 2269661 TI - cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals. AB - Sperm binding to the egg zona pellucida in mammals is a cell-cell adhesion process that is generally species specific. The guinea pig sperm protein PH-20 has a required function in sperm adhesion to the zona pellucida of guinea pig eggs. PH-20 is located on both the sperm plasma membrane and acrosomal membrane. We report here the isolation and sequence of a full-length cDNA for PH-20 (available from EMBL/GenBank/DDBJ under accession number X56332). The derived amino acid sequence shows a mature protein of 468 amino acids containing six N linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the COOH terminus. The sequence indicates PH-20 is a novel protein with no relationship to the mouse sperm adhesion protein galactosyl transferase and no significant homology with other known proteins. The two PH-20 populations, plasma membrane and acrosomal membrane, could arise because one form of PH-20 is encoded and differentially targeted at different spermatogenic stages. Alternatively, two different forms of PH-20 could be encoded. Our evidence thus far reveals only one sequence coding for PH-20: Southern blots of guinea pig genomic DNA indicated there is a single PH-20 gene, Northern blots showed a single size PH-20 message (approximately 2.2 kb), and no sequence variants were found among the sequenced cDNA clones. Cross-species Southern blots reveal the presence of a homologue of the PH-20 gene in mouse, rat, hamster, rabbit, bovine, monkey, and human genomic DNA, showing the PH-20 gene is conserved among mammals. Since genes for zona glycoproteins are also conserved among mammals, the general features of sperm and zona proteins involved in mammalian sperm-egg adhesion may have been evolutionarily maintained. Species specificity may result from limited changes in these molecules, either in their binding domains or in other regions that affect the ability of the binding domains to interact. PMID- 2269662 TI - The three-dimensional structure of the nemaline rod Z-band. AB - In nemaline myopathy and some cardiac muscles, the Z-band becomes greatly enlarged and contains multiple layers of a zigzag structure similar to that seen in normal muscle. Because of the additional periodicity in the direction of the filament axis, these structures are particularly favorable for three-dimensional analysis since it becomes possible to average the data in all three dimensions and thus improve the reliability of the reconstruction. Individual views of the structure corresponding to tilted longitudinal and transverse sections were combined by matching the phases of common reflections. Examination of the tilted views strongly suggested that to the available resolution, the structure possesses fourfold screw symmetry along the actin filament axes. This symmetry could be used both in establishing the correct alignment for the combination of individual tilted views and to generate additional views not readily accessible in a single tilt series. The reconstruction shows actin filaments from one sarcomere surrounded by an array of four actin filaments with opposite polarity from the adjacent sacormere. The actin filaments show a right-handed twist and are connected by a structure that links adjacent filaments with the same polarity at the same axial level, then runs parallel to the filaments, and finally forms a link between two actin filaments whose polarity is opposite to that of the first pair. The connecting structure is probably composed of alpha-actinin which is located in Z-bands and cross-links actin filaments. The connecting structure may consist of two alpha-actinin molecules linking actin filaments of opposite polarity. PMID- 2269663 TI - Microtubules are stabilized in confluent epithelial cells but not in fibroblasts. AB - Rhodamine-tagged tubulin was microinjected into epithelial cells (MDCK) and fibroblasts (Vero) to characterize the dynamic properties of labeled microtubules in sparse and confluent cells. Fringe pattern fluorescence photobleaching revealed two components with distinct dynamic properties. About one-third of the injected tubulin diffused rapidly in the cytoplasm with a diffusion coefficient of 1.3-1.6 x 10(-8) cm2/s. This pool of soluble cytoplasmic tubulin was increased to greater than 80% when cells were treated with nocodazole, or reduced to approximately 20% upon treatment of cells with taxol. Fluorescence recovery of the remaining two-thirds of labeled tubulin occurred with an average half-time (t1/2) of 9-11 min. This pool corresponds to labeled tubulin associated with microtubules, since it was sensitive to treatment of cells with nocodazole and since taxol increased its average t1/2 to greater than 22 min. Movement of photobleached microtubules in the cytoplasm with rates of several micrometers per minute was shown using very small interfringe distances. A significant change in the dynamic properties of microtubules occurred when MDCK cells reached confluency. On a cell average, microtubule half-life was increased about twofold to approximately 16 min. In fact, two populations of cells were detected with respect to their microtubule turnover rates, one with a t1/2 of approximately 9 min and one with a t1/2 of greater than 25 min. Correspondingly, the rate of incorporation of microinjected tubulin into interphase microtubules was reduced about twofold in confluent MDCK cells. In contrast to the MDCK cells, no difference in microtubule dynamics was observed in sparse and confluent populations of Vero fibroblasts, where the average microtubule half-life was approximately 10 min. Thus, microtubules are significantly stabilized in epithelial but not fibroblastic cells grown to confluency. PMID- 2269664 TI - Regulation of microtubule dynamics and nucleation during polarization in MDCK II cells. AB - MDCK cells form a polarized epithelium when they reach confluence in tissue culture. We have previously shown that concomitantly with the establishment of intercellular junctions, centrioles separate and microtubules lose their radial organization (Bacallao, R., C. Antony, C. Dotti, E. Karsenti, E.H.K. Stelzer, and K. Simons. 1989. J. Cell Biol. 109:2817-2832. Buendia, B., M.H. Bre, G. Griffiths, and E. Karsenti. 1990. 110:1123-1136). In this work, we have examined the pattern of microtubule nucleation before and after the establishment of intercellular contacts. We analyzed the elongation rate and stability of microtubules in single and confluent cells. This was achieved by microinjection of Paramecium axonemal tubulin and detection of the newly incorporated subunits by an antibody directed specifically against the Paramecium axonemal tubulin. The determination of newly nucleated microtubule localization has been made possible by the use of advanced double-immunofluorescence confocal microscopy. We have shown that in single cells, newly nucleated microtubules originate from several sites concentrated in a region localized close to the nucleus and not from a single spot that could correspond to a pair of centrioles. In confluent cells, newly nucleated microtubules were still more dispersed. The microtubule elongation rate of individual microtubules was not different in single and confluent cells (4 microns/min). However, in confluent cells, the population of long lived microtubules was strongly increased. In single or subconfluent cells most microtubules showed a t1/2 of less than 30 min, whereas in confluent monolayers, a large population of microtubules had a t1/2 of greater than 2 h. These results, together with previous observations cited above, indicate that during the establishment of polarity in MDCK cells, microtubule reorganization involves both a relocalization of microtubule-nucleating activity and increased microtubule stabilization. PMID- 2269665 TI - Functional mapping of SPARC: peptides from two distinct Ca+(+)-binding sites modulate cell shape. AB - Using synthetic peptides, we have identified two distinct regions of the glycoprotein SPARC (Secreted Protein Acidic and Rich in Cysteine) (osteonectin/BM 40) that inhibit cell spreading. One of these sites also contributes to the affinity of SPARC for extracellular matrix components. Peptides representing subregions of SPARC were synthesized and antipeptide antibodies were produced. Immunoglobulin fractions of sera recognizing an NH2-terminal peptide (designated 1.1) blocked SPARC-mediated anti-spreading activity. Furthermore, when peptides were added to newly plated endothelial cells or fibroblasts, peptide 1.1 and a peptide corresponding to the COOH terminal EF-hand domain (designated 4.2) inhibited cell spreading in a dose-dependent manner. These peptides exhibited anti-spreading activity at concentrations from 0.1 to 1 mM. The ability of peptides 1.1 and 4.2 to modulate cell shape was augmented by an inhibitor of protein synthesis and was blocked by specific antipeptide immunoglobulins. In addition to blocking cell spreading, peptide 4.2 competed for binding of [125I]SPARC and exhibited differential affinity for extracellular matrix molecules in solid-phase binding assays. The binding of peptide 4.2 to matrix components was Ca+(+)-dependent and displayed specificities similar to those of native SPARC. These studies demonstrate that both anti-spreading activity and affinity for collagens are functions of unique regions within the SPARC amino acid sequence. The finding that two separate regions of the SPARC protein contribute to its anti-spreading activity lead us to propose that multiple regions of the protein act in concert to regulate the interactions of cells with their extracellular matrix. PMID- 2269666 TI - Thrombospondin stimulates motility of human neutrophils. AB - Polymorphonuclear leukocytes (PMNs) migrate to sites of inflammation or injury in response to chemoattractants released at those sites. The presence of extracellular matrix (ECM) proteins at these sites may influence PMN accumulation at blood vessel walls and enhance their ability to move through tissue. Thrombospondin (TSP), a 450-kD ECM protein whose major proteolytic fragments are a COOH-terminal 140-kD fragment and an NH2-terminal heparin-binding domain (HBD), is secreted by platelets, endothelial cells, and smooth muscle cells. TSP binds specifically to PMN surface receptors and has been shown, in other cell types, to promote directed movement. TSP in solution at low concentrations (30-50 nM) "primed" PMNs for f-Met-Leu-Phe (fMLP)-mediated chemotaxis, increasing the response two- to fourfold. A monoclonal antibody against the HBD of TSP totally abolished this priming effect suggesting that the priming activity resides in the HBD of TSP. Purified HBD retains the priming activity of TSP thereby corroborating the antibody data. TSP alone, in solution at high concentrations (0.5-3.0 microM), stimulated chemotaxis of PMNs and required both the HBD and the 140-kD fragment of TSP. In contrast to TSP in solution, TSP bound to nitrocellulose filters in the range of 20-70 pmol stimulated random locomotion of PMNs. The number of PMNs migrating in response to bound TSP was approximately two orders of magnitude greater than the number of cells that exhibited chemotaxis in response to soluble TSP or fMLP. Monoclonal antibody C6.7, which recognizes an epitope near the carboxyl terminus of TSP, blocked migration stimulated by bound TSP, suggesting that the activity resides in this domain. Using proteolytic fragments, we demonstrated that bound 140-kD fragment, but not HBD, promoted migration of PMNs. Therefore, TSP released at injury sites, alone or in synergy with chemotactic peptides like fMLP, could play a role in directing PMN movement. PMID- 2269667 TI - Topologically restricted appearance in the developing chick retinotectal system of Bravo, a neural surface protein: experimental modulation by environmental cues. AB - A novel neural surface protein, Bravo, shows a pattern of topological restriction in the embryonic chick retinotectal system. Bravo is present on the developing optic fibers in the retina; however, retinal axons in the tectum do not display Bravo. The appearance of Bravo in vitro is modulated by environmental cues. Axons growing out from retinal explants on retinal basal lamina, their natural substrate, express Bravo, whereas such axons growing on collagen do not. Retinal explants provide a valuable system to characterize the mechanism of Bravo restriction, as well as the cellular signals controlling it. Bravo was identified with monoclonal antibodies from a collection generated against exposed molecules isolated by using a selective cell surface biotinylation procedure. The NH2 terminal sequence of Bravo shows similarity with L1, a neural surface molecule which is a member of the immunoglobulin superfamily. This possible relationship to L1, together with its restricted appearance, suggests an involvement of Bravo in axonal growth and guidance. PMID- 2269669 TI - Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure. AB - We have studied the expression of fibulin in cultured fibroblasts and determined its primary structure by cDNA cloning. Our results show that fibulin is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers. In addition, we find that fibulin is present in plasma at a level of 33 +/- 3 micrograms/ml. Sequencing of multiple fibulin cDNAs indicates that a process of alternative splicing results in the expression of three fibulin transcripts. The transcripts encode overlapping polypeptides differing only in carboxy-terminal segments. Common to the three predicted forms of fibulin is a unique 537-amino acid-long cysteine-rich polypeptide and a 29-residue signal peptide. The amino terminal portion of fibulin contains a repeated element with potential disulfide loop structure resembling that of the complement component anaphylatoxins C3a, C4a, and C5a as well as proteins of the albumin gene family. The bulk of the remaining portion of the molecule is a series of nine EGF-like repeats. PMID- 2269668 TI - Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes. AB - Basal cells of stratified epidermis are anchored to the basement membrane zone (BMZ) of skin via hemidesmosomes. We previously identified integrin alpha 3 beta 1, in focal adhesions (FAs), of cultured human keratinocytes (HFKs) as a mediator of HFK adhesion to secreted BMZ-like extracellular matrix (ECM; Carter, W.G., E.A. Wayner, T.S. Bouchard, and P. Kaur. 1990. J. Cell Biol. 110: 1387-1404). Here, we have examined the relation of integrins alpha 6 beta 4 and alpha 3 beta 1, to bullous pemphigoid antigen (BPA), a component of hemidesmosomes. We conclude that alpha 6 beta 4 in HFKs localizes in a new stable anchoring contact (SAC) that cooperates with alpha 3 beta 1-FAs to mediate adhesion to ECM, based on the following. (a) Comparison of secreted ECM, with exogenous laminin, fibronectin and collagen identified ECM as the preferred ligand for HFK adhesion and spreading and for formation of both alpha 6 beta 4-SACs and alpha 3 beta 1 FAs. (b) Inhibition of HFK adhesion with combined anti-alpha 3 beta 1 (P1B5) and anti-alpha 6 beta 4 (GoH3) antibodies indicated that both receptors were functional in adhesion to ECM while alpha 3 beta 1 played a dominant role in spreading. (c) alpha 6 beta 4 colocalized with BPA in SACs that were proximal to but excluded from FAs. Both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs were in contact with the adhesion surface as indicated by antibody exclusion and interference reflection microscopy. (d) In contrast to alpha 3 beta 1-FAs, alpha 6 beta 4-SACs were present only in nonmotile cells, not associated with stress fibers, and were relatively stable to detergents and urea, suggesting a nonmotile, or anchoring function for SACs and motility functions for alpha 3 beta 1-FAs. (e) alpha 6 beta 4 formed a detergent-insoluble complex with exogenous ECM in an affinity isolation procedure, confirming the ability of an unidentified ECM ligand to interact with alpha 6 beta 4. (f) We suggest that alpha 6 beta 4/BPA SACs in culture restrict migration of HFKs on ECM while alpha 3 beta 1-FAs form dynamic adhesions in spreading and migrating cells. alpha 6 beta 4/BPA-SACs in culture bear functional and compositional similarities to hemidesmosomes in skin. PMID- 2269671 TI - Helping parents to decide what is best for their child. AB - Helping parents to decide what is best for their child is a necessary portion of medical management for the injured, anomalous, or sick child. It involves collecting information about, consideration of, and giving advice concerning much more than medical details. Certain steps are suggested in offering this help: (1) obtaining comprehensive medical, socioeconomic, and psychologic information; (2) packaging this information to inform fully and satisfy the parents/surrogates of the child; (3) confirming the family's informed participation in the treatment decision; and (4) reinforcing that decision with a very supportive and communicative perioperative period. PMID- 2269670 TI - Interaction of the NG2 chondroitin sulfate proteoglycan with type VI collagen. AB - The NG2 chondroitin sulfate proteoglycan is a membrane-associated molecule of approximately 500 kD with a core glycoprotein of 300 kD. Both the complete proteoglycan and a smaller quantity of the 300-kD core are immunoprecipitable with polyclonal and monoclonal antibodies against purified NG2. From some cell lines, the antibodies coprecipitate NG2 and type VI collagen, the latter appearing on SDS-PAGE as components of 140 and 250 kD under reducing conditions. The immunoprecipitation of type VI collagen does not seem to be due to recognition of the collagen by the antibodies, but rather to binding of the collagen to NG2. Studies on the NG2-type VI collagen complex suggest that binding between the two molecules is mediated by protein-protein interactions rather than by ionic interactions involving the glycosaminoglycans. Immunofluorescence double labeling in frozen sections of embryonic rat shows that NG2 and type VI collagen are colocalized in structures such as the intervertebral discs and arteries of the spinal column. In vitro the two molecules are highly colocalized on the surface of several cell lines. Treatment of these cells resulting in a change in the distribution of NG2 on the cell surface also causes a parallel change in type VI collagen distribution. Our results suggest that cell surface NG2 may mediate cellular interactions with the extracellular matrix by binding to type VI collagen. PMID- 2269672 TI - The pediatric upper extremity. PMID- 2269673 TI - Radial polydactyly. AB - Excessive longitudinal segmentation of the radial portion of the limb bud results in the clinical presentation of duplicated and triphalangeal thumbs. These are common congenital problems with various possible associated anomalies and variable inheritance patterns. Reconstruction of a thumb with stable joints, muscle balance, and good alignment requires attention to each tissue component at the time of the initial surgery. PMID- 2269674 TI - Management of radial dysplasia. AB - An appreciation of the clinicopathologic presentation of children with radial dysplasia (radial club hand) is important. Management decisions depend upon the degree of radial ray defect present; in most cases these are surgical. Current surgical options favor centralization without resection of carpal bones, stabilized by tendon transfers. When the thumb ray is deficient, pollicization is a rewarding procedure. PMID- 2269675 TI - Digital augmentation for ectrodactyly: management and planning. AB - Selection of the most appropriate operations for a patient is as important as technical expertise in performing the procedures. Web deepening may be performed alone or in addition to tissue augmentation and should be planned in conjunction with bone lengthening. Skeletal augmentation is useful if fingers are missing or inadequate, and it is necessary to add bony tissue. In general, in order to grow, skeletal transfers must be performed on very young children or must include vascularized physes; complex cases may require microvascular composite toe-to hand transfer. Distraction-lengthening for intercalary skeletal enhancement is indicated for patients with multiple hypoplastic, aplastic, and missing digits, but the cosmetic result is limited. The major procedures should be started by age 2 years and finished by age 4; unfortunately, it is most often not advisable to perform microvascular surgery at such an early age. Modification of functional patterns, even though they are abnormal or the result of incomplete anatomy, should be avoided in the older child or adult because tinkering does not lead to significant benefits. For a cooperative, and often difficult, staged venture to be maximally successful, physicians and parents must share realistic expectations of aesthetic and functional results. PMID- 2269677 TI - The role of nonvascularized toe phalanx transplantation. AB - Stabilization of boneless finger stumps or lengthening of partially aplastic digits in congenital malformations is difficult, because the bone graft, placed on top of the existing bone, will undergo resorption. Only the periosteum-covered proximal toe phalanx will withstand resorption and show a complete take. With the toe phalanx, including the plantar plate and the collateral ligaments of the metatarsophalangeal joint as a half-joint, it is possible to construct a new joint with the cartilage-covered distal end of the recipient bone (metacarpal or proximal phalanx) as the proximal half-joint. Flexor and extensor tendons exist in almost all cases. Between 1976 and 1990, 97 toe phalanx transplantations were performed in 57 children. The indications were boneless digital stumps with partial absence of digits and large bone defects in fingers in symbrachydactyly and ring-constriction syndrome. Follow-up examinations of 44 patients with 69 transplanted toe phalanges (95% of the patients operated on by March 1989) have shown a 100% take of the bone graft, provided it had been unsplit and the periosteal cover undamaged. The earlier in life the operation was performed, the more postoperative growth was recorded. The shortening of the donor toe was less because a tendon interposition was used. A joint construction was attempted in 64 digits with variable results. The range of active motion varied between 0 (fusion) and 90 degrees. PMID- 2269678 TI - Hand involvement in multiple hereditary exostosis. AB - In summary, patients with multiple hereditary exostosis often inherit hand involvement but rarely show hand deformity. The principal area of involvement appears to be around the MCP joint but the PIP joint is the most common area of deformity. Metacarpal shortening usually does not cause functional problems and need not be treated. Angular deformity, though rare, does cause problems and needs surgical treatment. Unfortunately, there is no evidence that prevention of deformity is possible by early excision of osteochondromas. Treatment, therefore, requires both osteochondroma excision and closing-wedge corrective osteotomy. PMID- 2269676 TI - Management of thumb hypoplasia. AB - This chapter emphasizes the dilemma of salvage and reconstruction of the congenitally aplastic or hypoplastic thumb without normal cerebrocortical representation for prehensile grasp and pinch. The philosophy of reconstruction of the congenitally anomalous thumb is clearly divergent from thumb reconstruction following trauma. It is difficult to advise parents who seek surgical correction of the severely deficient thumb ray that amputation is the procedure of choice, to be followed by transfer of an otherwise normal digit to become a functional thumb unit. The psychological impact of these recommendations may be devastating to parents. Informed understanding of the likely progressive development of index-middle finger scissoring, pronation of the index ray with spontaneous broadening of the pulp, and the deteriorating use of an existing hypoplastic thumb may make the decision for ablation easier for parents. It is critical that these decisions be made through careful education and understanding, considering always the overall grasp-and-pinch capability of the hand as a whole. Reconstruction of the aplastic or hypoplastic thumb is an exciting and challenging area of hand surgery. The rewards are improvement in grasp and pinch either by functional integration of the reconstructed part, or by complete replacement of the deficient thumb by tissue from adjacent or distant donor sites. Success is measured not only in terms of cosmetic appearance, but as enhanced capacity of the child's hand in all activities of daily living (Fig. 39A and B). PMID- 2269679 TI - Postoperative splinting of the pediatric upper extremity. AB - The protective splint described above provides appropriate immobilization and protection for our postoperative pediatric population. The major advantages of this splint over plaster of paris include direct access to the wound, easy reapplication, and unnecessary use of the plaster-cast saw. In addition, thermoplastic splints are lightweight, less bulky, more durable, water-resistant, and easily remolded. The therapist's approach to the patient and parents is of utmost importance and will affect the outcome of the splint. In conclusion, postoperative pediatric splinting can be a challenging experience that requires a significant amount of patience, knowledge, and creativity on the part of the hand therapist. PMID- 2269680 TI - Cerebral palsy of the upper extremity. AB - The care of patients with spastic cerebral palsy requires the dedicated attention of a surgeon who is interested in the upper extremity, in association with therapists and other medical personnel who have a similar interest. The difficult problems of the upper extremity have often been overlooked by concerns related to the other skeletal manifestations in the spine and lower extremities. However, a pessimistic view of surgical results in the upper extremity is unwarranted, as even small gains in severely affected patients often result in an improved life. The surgical concepts related to this complex neurologic problem must be kept rather simple, and include principally the release of spastic deforming muscles, and, secondly, the use of augmentation tendon transfers to maintain an improved functional position. In order to allow the augmentation tendon transfers to function with minimal postoperative muscle re-education, tendon transfers that use muscles that contribute to the deformity are preferred; in the transferred position, these will function to correct the deformity and fire in phase without extensive postoperative training. Such muscle transfers are usually available to correct the more common pattern of spastic deformities. The most important aspect of surgical planning is to determine whether or not the individual is attempting to voluntarily use the upper extremity. In such cases, surgical procedures can reposition the deformed limb and enable the individual to function more effectively. On the other hand, it is most important to realize that an operative procedure will not stimulate an individual to begin to use a previously functionless limb. PMID- 2269681 TI - Management of burns of the hands in children. AB - Burns of the hand occur in children when the infant or toddler suffers a scald burn or a contact burn to the palm of the hand. Older children frequently suffer burns from experimenting with matches or gasoline. Although burns of the hand in children are not always as deep as in adults, optimal treatment involves the correct acute management, with skin grafting and proper splinting and physical therapy playing a large role, as well as long-term follow-up due to the excessive scar tissue that may form and the continued growth of the child's hand. The psychosocial needs of the burned child, including an understanding of the nature of child abuse and/or neglect, are also important. PMID- 2269682 TI - Wrist and hand skeletal injuries in children. AB - When accidents occur, the hand is the part of the body most often thrust out to lessen the consequences, resulting in a wide array of combinations of soft-tissue and chondro-osseous injuries. Pediatric wrist and hand skeletal injuries discussed in this article include growth mechanism injury, fractures and dislocations, nailbed injuries, fingertip injuries, burns, and frostbite. PMID- 2269683 TI - Differentiation of BC3H1 and primary skeletal muscle cells and the activity of their endogenous insulin-degrading enzyme are inhibited by the same metalloendoprotease inhibitors. AB - Upon reduction of serum in their media, mouse BC3H1 muscle cells withdraw from the cell cycle and begin to differentiate. In differentiating cells, the induction of muscle-specific genes is accompanied by a distinct morphological chance. However, differentiated BC3H1 cells do not fuse with each other; they remain mononucleated. Metalloendoprotease inhibitors selectively block the differentiation of BC3H1 cells while inhibitors of other protease types are ineffective. In these cells, the degradation of the internalized insulin is initiated by a 110 kDa, non-lysosomal protease known as the insulin-degrading enzyme. The same metalloendoprotease inhibitors that block BC3H1 differentiation also inhibit, with a similar specificity and potency, the in vitro and the in vivo degradation of insulin by the insulin-degrading enzyme. When the serum in the medium is reduced, the activity of the insulin-degrading enzyme in the cell cytoplasm increases rapidly. This increase precedes any detectable change in the differentiation state of these cells by about 12 hours. These results, together with very similar ones obtained with primary rat skeletal muscle cells, support our earlier proposal that the insulin-degrading enzyme is the metalloendoprotease involved in the initiation of the morphological and biochemical differentiation of muscle cells in culture. PMID- 2269684 TI - Expression of a 64 kD adipocyte-specific plasma membrane protein in genetically lean but not obese porcine adipocytes. AB - A monoclonal antibody (LA-1) to an adipocyte-specific plasma membrane protein (64 kD) was used to examine the differential expression of this protein in genetically lean and genetically obese pigs. Enzyme-linked immunosorbent assay (ELISA) implied the differential expression of the 64 kD protein in adipocyte plasma membranes having different genetic background. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of genetically lean, genetically obese, and contemporary subcutaneous adipocyte plasma membranes did not indicate any obvious qualitative differences in protein composition. Corresponding immunoblots utilizing LA-1 confirmed the presence of the 64 kD protein in contemporary and genetically lean adipocyte plasma membranes but absence in genetically obese adipocyte plasma membranes. LA-1 labelled intact adipocytes isolated from contemporary and genetically lean adipose tissue but did not react with isolated genetically obese adipocytes. The ability to bind to intact adipocytes indicates that the protein is exposed to the extracellular environment. The migration pattern of the protein was not affected by enzymatic deglycosylation by endoglycosidase-F suggesting that the protein is not highly, if at all, glycosylated. Presence of the 64 kD protein in genetically lean but not genetically obese adipocyte plasma membranes indicates the identification of a novel adipocyte-specific surface protein associated, either directly or secondary to the onset of obesity, with genetic predispositions for either genetically lean or obese body types in swine. PMID- 2269685 TI - Multiple types of mRNA-cytoskeleton interactions. AB - Nearly all actively translated mRNAs are associated with the cytoskeleton in HeLa cells and the nature of this association is poorly understood. To gain insight into this association, we have examined and compared the cytoskeleton-mRNA interactions of a signal peptide-histone fusion mRNA (membrane-bound polysomal mRNA) to those of endogenous histone mRNA (nonmembrane-bound polysomal mRNA). We report here the detection of a cytoskeleton attachment site within the signal peptide-histone fusion mRNP/mRNA nucleotide sequence that is not present in wild type histone mRNA or in HLA-B7 and chorionic gonadotropin-alpha membrane-bound polysomal mRNAs. These results support the possibility that there are multiple mechanisms for the attachment of specific classes of mRNAs to the cytoskeleton. PMID- 2269687 TI - [Therapeutic diagram in advanced cancers of the esophagus]. AB - Only palliative treatment may be contemplated when advanced oesophageal cancers present with dysphagia. Operability depends on respiratory, hepatic and nutritional status. Resectability may be assessed on the information provided by bronchoscopy, thoracic CT scan and surgical exploration. Advanced resectable oesophageal cancers require oesophagectomy without thoracotomy and radiotherapy. We performed 93 oesophagectomies in 106 advanced oesophageal cancers with a mortality rate of less than 2%. Non resectable advanced oesophageal cancers require bypass procedures. We performed 13 in the 106 cases. Inoperable advanced oesophageal cancers require radiotherapy in the absence of a fistula, laser therapy or an endoprosthesis for dysphagia. PMID- 2269686 TI - [Repeated subinguinal bypass. Report of 85 cases]. AB - From 1975 to 1987, 68 patients were operated with repeated subinguinal bypass (SIB) following early or late thrombosis os an initial bypass graft; 10 were operated with a third SIB, 4 with a fourth SIB. The indication for the second SIB was acute ischemia in 15 cases and chronic ischemia in 53. The graft material used was venous in 21 cases, prosthetic in 29 cases and mixed in 53. The distal anastomosis was performed on the upper popliteal artery in 12 cases, the lower popliteal artery in 34 cases or an artery in leg in 22 cases. The actuarial permeability rate of 84 repeated SIBs, whatever the material, was 21.7% at 1 year (50.2% for venous grafts and 13.6% for prosthetic grafts). The limb preservation rate was 47.9% at 5 years. Operative mortality was about 1%. The analysis of the results suggests that the repeated SIB should be performed only: for limb salvage, if the downstream arterial bed is in good condition, with usable venous material. The risk of having to perform a thigh amputation rather than a leg amputation when attempting repeated SIB is of 13.9% only. PMID- 2269688 TI - [Post-traumatic hemarthrosis of the knee and arthroscopy. Review of 161 cases]. AB - In a prospective study, 161 traumatic hemarthrosis of the knee had clinical, radiological and arthroscopic examination. The anatomical lesions were diagnosed clinically and radiologically in 78%, but was incomplete every other time. Arthroscopy allowed us to confirm, to complete or to do the exact diagnosis in 98%. Anatomical lesions were never benign: ligaments ruptures (65%), patella dislocations (20.5%), chondral lesions (41%), meniscal lesions (31%). The main interest of arthroscopy is to precise associated lesions and thus, to use these data for a rational treatment program. Most often, the treatment has been performed by arthroscopic techniques, avoiding arthrotomy and shortening post operative rehabilitation. No complication due to arthroscopy has been noted. This study confirms: (1) that a traumatic hemarthrosis indicates a serious knee injury, and (2) the important contribution of arthroscopy for diagnosis and treatment of these traumatic knees. PMID- 2269689 TI - [Ledderhose's disease. Report of 7 cases]. AB - Ledderhose's syndrome, or plantar fibromatosis, is a rare fibrous dystrophy and the plantar equivalent of Dupuytren's disease. It occurs mainly in adult subjects, as a plantar fibrous nodule. The authors report 7 operated cases of Ledderhose's syndrome, including one in a 14-year-old adolescent. When the plantar nodule becomes symptomatic, surgery is the only means of treatment. Plantar aponeurotomy must then be as extensive as possible to prevent recurrent. PMID- 2269690 TI - [Primary abscess of the psoas. 2 new cases]. AB - Since the antibiotherapy for tuberculosis, psoas abscess is an infrequent disease. The psoas abscess can be divided in primary and secondary, being the primary the most infrequent. We present two other cases of primary psoas abscess treated in our hospital. We review also the symptoms, the diagnosis and the therapy of this disease. PMID- 2269691 TI - [Volvulus of the sigmoid. Review of 38 cases]. AB - A retrospective study of 38 cases of sigmoid volvulus is reported. The relative frequency of this pathology among young people in Morocco is noted. In 82% of cases diagnosis was without difficulty; and in two cases an associated small bowel volvulus was found. When deciding on the therapeutic approach it is essential to differentiate between cases in which the sigmoid colon is necrotic and those in which the changes are reversible. In the latter, the authors recommend a non surgical reduction (using flatus tube or better: colonoscopy with elective surgery performed at later date. If initial reduction proves impossible, colonic resection with colostomy appears to give the best results. PMID- 2269693 TI - [Urethroplasty using a pedicled skin graft in one-stage treatment of urethral stenosis. Review of 87 cases]. AB - 118 cases of urethral stenosis treated by the same surgeon from September, 1984, to December, 1989, have led the author to describing a one-stage technique for the surgical treatment of urethral stenosis using a widening implant or a pedicled penoscrotal tube. This technique is patterned on ORANDI's and BLANDY's procedures and utilizes a pedicled skin graft taken from a remote, therefore unaffected, site. 87 patients were treated with this procedure for urethral stenosis, often complicated by infection and fistulae, 34 after the failure of previous treatment. With a distance in time exceeding 2 years for most operated cases, the percentage of satisfied patients is of about 95%. The results were estimated according to the quality of urination, to the strength of the urine flow, to micturating and retrograde pyelography and to a fiberendoscopic checkup. In 71 cases (81.6%), the result was rated as good, immediately in 66 cases, after a second operation in 4 and after 3 operations in 1 case. The results were regarded as average in 12 cases (13.5%) and poor in 4 cases (4.6%). Cutaneous urethroplasty using a pedicled skin flap is relatively easy and represents an excellent procedure for the treatment of urethral stenosis owing to the low rate of failure and to the quality of the results obtained. The author stresses the advantages of grafting a well-vascularized skin flap, which is particularly indicated, whatever the site and extent, in cases of urethral stenosis with infection, fistulae or following several operations, the pedicled skin graft being a procedure of choice for all these aggravating factors. PMID- 2269692 TI - [Surgical treatment of sigmoid diverticulitis]. AB - Diverticular disease is generally benign but may be life threatening should progressive complications occur. Under these circumstances cure may only be obtained if properly performed surgery is undertaken at the right moment. The end result of a low fibre diet, diverticular disease may affect the entire colon, but always tends to particularly affect the sigmoid region. This is the usual site of complications where the etiology is related to diverticular infection associated with fecal impaction proximal to the high pressure zone at the recto-sigmoid junction. The radical treatment of sigmoid diverticulitis is rectosigmoid resection, however, this concept may be altered according to the circumstances as follows: 1 - sigmoid diverticulitis without pericolic complications 2 - peri sigmoid complications: peri-sigmoid abscess, intestinal and vesical fistulae. 3 - generalised peritonitis due to perforation into the peritoneal cavity. The advanced age of the patient should be stressed (mean age 65 years and 25% over 75 years) associated with a high incidence of multiple organ failure and hence the high mortality in more than 50% of cases in the event of peritonitis. PMID- 2269694 TI - [Sigmoid perforation in an ovarian cyst]. PMID- 2269695 TI - [Destruction of the common bile duct caused by hydatid cyst of the liver]. PMID- 2269696 TI - [Fracture-dislocations of Lisfranc's joint: a rarity?]. PMID- 2269697 TI - Fine-tuning of utterance length to preverbal infants: effects on later language development. AB - The purpose of this study was to determine (1) whether mothers simplify their speech during the second half of the first year of development when infants begin to comprehend words and use gestures to communicate intentionally, and (2) whether individual differences in mothers' speech adjustments influence their infants' later language acquisition. The subjects for the study were 14 mother infant pairs from a medically low risk sample who were followed longitudinally. Mothers' mean length of utterance (MLU) was calculated from transcripts of face to-face interaction when the infants were 0:3, 0:6, and 0:9 in age. Mothers who provided responsive and stimulating environments, as indicated by HOME scores, also reduced their MLU over the age range studied. Moreover, mothers' MLU adjustments during the first year were more predictive than the HOME scale in forecasting receptive language development at 1:6. In contrast, expressive language abilities at 1:6 were unrelated to the environmental variables measured but were predicted by child characteristics such as the infant's sex. These results suggest that a mother's ability to 'fine-tune' her early linguistic input may be predictive of her child's later receptive language functioning. Precursors of fine-tuning, such as maternal beliefs in reciprocity and infant object orientation, are discussed. PMID- 2269698 TI - The role of parental input in the development of a morphological system. AB - In order to isolate the properties of language whose development can withstand wide variations in learning conditions, we have observed children who have not had access to any conventional linguistic input but who have otherwise experienced normal social environments. The children we study are deaf with hearing losses so severe that they cannot naturally acquire spoken language, and whose hearing parents have chosen not to expose them to a sign language. In previous work, we demonstrated that, despite their lack of conventional linguistic input, the children developed spontaneous gesture systems which were structured at the level of the sentence, with regularities identifiable ACROSS gestures in a sentence, akin to syntactic structure. The present study was undertaken to determine whether one of these deaf children's gesture systems was structured at a second level, the level of the gesture-that is, were there regularities WITHIN a gesture, akin to morphologic structure? We have found that (1) the deaf child's gestures could be characterized by a paradigm of handshape and motion combinations which formed a matrix for virtually all of his spontaneous gestures, and (2) the deaf child's gesture system was considerably more complex than the model provided by his hearing mother. These data emphasize the child's contribution to structural regularity at the intra-word level, and suggest that such structure is a resilient property of language. PMID- 2269699 TI - Discourse and the acquisition of grammatical morphemes. AB - Adult recasts of child utterances have been shown to be related in a general way to the child's acquisition of syntactic structures. The current study had two aims. The first aim was to determine which feature(s) of recasts (i.e. reformulation, expansion, topic continuation, or reply) was responsible for facilitating language acquisition by comparing them to other maternal discourse models that were systematically defined by these properties. The second aim was to investigate this relation more specifically by relating adult discourse models of specific grammatical morphemes to the child's acquisition of those same morphemes. Again, recasts were of particular interest. Twelve mother-child dyads were videorecorded during one hour of naturalistic interaction when the children were 1; 10 and 2; 4. Results indicated that maternal recasts of specific morphemes were related to the acquisition of those same grammatical morphemes during certain developmental periods, whereas other grammatical morphemes were facilitated by expansions and topic continuations. These results are discussed in terms of the processes responsible for these effects. PMID- 2269700 TI - Referential style at thirteen months: why age-defined cross-sectional measures are inappropriate for the study of strategy differences in early language development. AB - This study examines the relationship between cross-sectional measures of referential style taken at 1; 1 and measures based on the first 50 words in 12 first-born children. Since no significant relationship is found it is argued that age-defined cross-sectional measures are inappropriate for the study of strategy differences in early language development because they confound such differences with variation due to differences in development level. PMID- 2269701 TI - From one word to two words: repetition patterns on the way to structured speech. AB - This paper gives an account of the transition from one-word to multi-word utterances based on the productions of one child from age 1; 5.23 to 1; 8.15 in spontaneous interaction with her mother. The authors' interpretation of the observed development emphasizes: (1) the initial dissociation and later co ordination of temporal chaining of elements on the one hand and meaning relatedness between elements on the other; and (2) the psychological importance of repetition patterns for the change from single-word functioning to meaning related and temporally-chained multi-word utterances, i.e. utterances that show the duality of patterning characteristic of human language. PMID- 2269702 TI - The development of sentence planning. AB - This is an exploratory case study of the relation between speech output disturbances (dysfluencies) and the development of language production processes. The data consist of transcribed weekly speech samples of a Dutch boy between 2;4 and 2;11. The period of observation captures the early phase of the transition from 'pre-grammatical' to grammatical language. The frequency of occurrence of dysfluencies (i.e. repetitions, revisions and incomplete phrases) shows a significant increase and a subsequent decline. Whereas in the first half of the observation period the dysfluencies are distributed relatively randomly over sentences, in the second half they tend to concentrate in function words and sentence-initial words. The decline of dysfluency rate is shown to be related to an abundant use of a few 'syntactic frames'. It is argued that these results reflect the emergence of a component in the speech production apparatus which is specifically dedicated to serial-order planning. PMID- 2269703 TI - Acquisition of passives: the role of patient animacy, salience, and lexical accessibility. AB - In full passive sentences such as The cat was kicked by the dog, the patient (cat) is promoted to subject and the agent is demoted to the by-phrase. Children 2;10 to 4;7 years (mean 3;6) who were taught the form with animate patients and animate agents (The baby is being picked up by the girl) were better able to produce and comprehend passives than children taught with inaminate patients and animate agents (The flower is being picked up by the girl). The finding of comparable post-teaching performance in children taught with perceptually salient (coloured) vs. nonsalient patients argues against a salience explanation for the patient animacy effect. Moreover, equal access to word forms for animate effect is inanimate nouns did not reduce the effect. The animacy effect is consistent with claims that 'perspective' is the cognitive counterpart to the formal category of subject; and, conversely, inconsistent with attempts to understand language acquisition in terms of a language system that operates in isolation from other facets of human cognition. PMID- 2269704 TI - The development of definitional skill. AB - Giving good definitions requires controlling both word meaning and definitional form. Definitions from 137 second to fifth graders (i.e. aged seven to eleven) were scored to reflect conformity to the classic Aristotelian form and quality of information provided. Comparisons among children with different backgrounds indicated that school exposure to English was strongly related to per cent formal definitions given and their quality. 63 children were also tested in French, their foreign language. Performance in French was lower than in English; exposure to French at home related to the amount of information the children provided in informal definitions, not to quality of formal definitions. The results suggest that performance on definitions is most strongly affected by opportunities to practise the required form. PMID- 2269705 TI - Input evidence regarding the semantic bootstrapping hypothesis. AB - The input language addressed to 18 language-learning children (MLU 1.00-3.00) was analysed so as to assess the quality of the semantic-syntactic correspondence posited by the semantic bootstrapping hypothesis. The correspondence appears to be quite satisfactory with little variation from the lower to the higher MLUs. All the persons and things referred to in the corpora were labelled by the mothers using nouns. All the actions referred to were labelled using verbs. Most of the attributive information was conveyed by adjectives. Spatial information was expressed through the use of spatial prepositions. As to the functional categories, all agents of actions and causes of events were encoded as subjects of sentences. All patients, themes, sources, goals, locations, and instruments were encoded as objects of sentences (either direct or oblique). This good semantic-syntactic correspondence may make the child's construction of grammatical categories easier. PMID- 2269706 TI - Characterization of primers for optimal amplification of hepatitis B virus DNA in the polymerase chain reaction assay. AB - While the polymerase chain reaction assay has been shown to be effective in detecting serum hepatitis B virus (HBV) DNA, a systematic evaluation of the characteristics of optimal primer pairs has not yet been reported. Several factors related to the selection of primer pairs were examined and the findings are summarized as follows: (1) primers specific for the single- or double stranded region of the HBV genome are equally effective in amplifying serum DNA; (2) maximum amplification is seen using primers, separated by no more than 500 nucleotides; and, (3) primers with up to 14% mismatch are effective at amplifying HBV DNA. PMID- 2269707 TI - The meaning of cardiac output. PMID- 2269708 TI - Measuring the breathing workload in mechanically ventilated patients. PMID- 2269709 TI - An adequate strategy for the thermodilution technique in patients during mechanical ventilation. AB - The application of the thermodilution method in conditions associated with variations in blood flow implies a misuse of the Stewart Hamilton equation. Therefore, we studied the reliability of the thermodilution method for the estimation of mean cardiac output (CO) during mechanical ventilation in patients (n = 9). Variation of the injection moment in the ventilatory cycle elicited a cyclic variation of CO estimates. This variation was not the same for all patients neither in phase nor in amplitude. Therefore, no specific phase in the ventilatory cycle could be selected for an accurate estimation of mean CO. Averaging CO estimates randomly distributed in the ventilatory cycle led to an improvement of accuracy with the square root of the number of observations. The averaging of CO estimates spread equally over the ventilatory cycle led to a much better result, e.g., the variation in the average of two estimates equally spread in the ventilatory cycle was similar to the variation in the average of four random estimates. We conclude that averaging of 3 or 4 estimates spread equally over the ventilatory cycle is an adequate strategy to estimate mean cardiac output in patients reliably. PMID- 2269711 TI - Thromboxane and prostacyclin release after endotoxin infusion in the rat. AB - To determine in the rat whether pulmonary artery hypertension accompanies thromboxane release, we sequentially monitored pulmonary and systemic artery pressures and cardiac output. We measured pulmonary and aortic plasma levels of TxB2 as well as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in awake unrestrained adult male Sprague-Dawley rats given a single infusion of endotoxin at the relatively high dose commonly administered to this endotoxin-resistant species. At 40 min after endotoxin infusion, both pulmonary and aortic TxB2 and 6 keto-PGF1 alpha levels increased nine-fold and seven-fold above baseline, respectively. In the pulmonary artery, 40 min after infusion, both mediator levels differed significantly from baseline (p less than 0.05), whereas in the aorta, because of marked variance in the response of different animals, only the 6-keto-PGF1 alpha levels achieved significance (p less than 0.05). These changes were associated with a fall in systemic blood pressure and cardiac output, but no demonstrable rise in pulmonary artery pressure (PAP). Despite ultrastructural evidence of vascular injury, these data indicate that in the rat thromboxane and prostacyclin release following a single infusion of endotoxin is not associated with pulmonary hypertension and that increased prostacyclin production may contribute to systemic hypotension. PMID- 2269710 TI - Intensive care management of children following heart and heart-lung transplantation. AB - We report the intensive care management of 23 children (age 3-15 years) following orthotopic heart (HT) and combined heart and lung transplantation (HLT) performed at our 2 institutes between February 1985 and August 1989. Cyclosporin A, azathioprine and steroids were given as routine immunosuppression, whilst anti thymocyte globulin (ATG) was used for the first 3 post-operative days. Mean ventilation time was 24.6 h (range 4-74 h). Cardiovascular support comprised isoprenaline infusions in all patients (mean period 65.7 h) whilst dopamine and other inotropic agents were used less frequently. Sequential atrioventricular pacing was required more often in the HT patients (n = 9) than in the HLT patients (n = 4). Fluid input was restricted to maintain a plasma osmolality of 290-300 mosm/kg. There were 2 perioperative deaths both due to acute right heart failure. Other post-operative complications included: bleeding (n = 3); acute graft rejection (n = 4); infection (n = 3); systemic hypertension (n = 6); neurological abnormalities (n = 2); renal dysfunction (n = 6) and hyperglycaemia (n = 6). PMID- 2269712 TI - Effects of the heat-moisture exchangers on dynamic hyperinflation of mechanically ventilated COPD patients. AB - In recent years the use of devices called Heat and Moisture Exchangers (HME) has become widespread as gas conditioners for ICU patients requiring mechanical ventilation. As an important variation of the resistive properties of the HME, related to flow and duration of use, has recently been pointed out during "in vitro" studies, the use of these devices in COPD patients could increase the levels of auto PEEP and dynamic hyperinflation. In this study we have compared the levels of auto PEEP and difference in functional residual capacity (delta FRC) in a group of COPD patients, requiring controlled mechanical ventilation (CMV), at basal conditions and after the insertion into the circuit of three HMEs (Dar Hygrobac, Pall Ultipor, Engstrom Edith) at random: the results obtained excluded a significant increase of auto PEEP and delta (FRC) both with "new" HMEs and after 12 h of continuous use. PMID- 2269713 TI - Free radical-induced lipoperoxidation and severe head injury. A clinical study. AB - Ten severely head injured patients (GCS less than or equal to 8), aged 17-62 years, were studied in order to investigate the role of lipoperoxidation in secondary brain damage. No patients had intracranial mass lesions, shock, hypoxemia, fever or sepsis. Blood samples were taken from the jugular bulb and from the right atrium, and thiobarbituric acid reacting substances (TBARS) were measured in plasma by spectrophotometry. Arterio-jugular venous oxygen differences (AVDO2) were obtained in seven patients, in order to estimate cerebral blood flow. Jugular TBARS (TBARSj) were always elevated (from To, to 2 h after injury) and correlated in a linear fashion with TBARS of right atrium (TBARSv): r = 0.74, p less than 0.001. TBARSj and AVDO2 are closely correlated, in accordance with an exponential function (R = 0.45, p less than 0.001) which describes how any cerebral perfusion derangement determines high levels of TBARSj, confirming lipoperoxidation as a key factor in the final common pathway of secondary posttraumatic brain damage. PMID- 2269714 TI - Clearance of ceftriaxone in critical care patients with acute renal failure. AB - Serum concentrations of ceftriaxone (RocephinTM), a third generation cephalosporin, were monitored in 5 operative intensive care patients suffering from acute renal failure (ARF) and compared to those of 7 patients without renal disturbance. For a period of 7 days, a fixed dose of 2 g/day was given by a 15 min infusion. Pharmacokinetic parameters were calculated by fitting all serum and urine data measured over the period of treatment. Ceftriaxone free fraction was measured on days 2 and 7. There was no evidence for an intraindividual change in ceftriaxone-clearance during the observation period. Ceftriaxone renal clearance was closely dependent on creatinine clearance according to a linear regression expressed by Clren = 0.14 Clcrea + 2.2 (r = 0.951, p less than 0.0001). Total clearance was also associated with creatinine clearance: Cltot = 0.19 Clcrea + 8.2 (r = 0.964, p less than 0.0001). Related to the free fraction, renal clearance was in the range of the glomerular filtration rate. Non-renal clearance was strongly decreased when related to the free fraction indicating that biliary excretion is also impaired in patients with acute renal failure. Obviously no compensatory increase in hepatic ceftriaxone clearance takes place. It is concluded that elimination of ceftriaxone may be strongly impaired during acute renal failure in surgical intensive care patients and that dosage should be restricted according to degree of the impairment of creatinine clearance. PMID- 2269715 TI - Failure of the intracaval filter of Gunther to prevent recurrence of pulmonary embolism--report of two cases. AB - Two out of nine patients in which inferior vena cava interruption was performed with a Gunther filter developed a recurrent pulmonary embolism. In both cases, the filter had moved down and the anchoring legs had perforated the wall of the vena cava. The source of the pulmonary embolism was a clotted basket filter. Anticoagulation was given for two weeks in one patient and six months in the other after insertion of the filter, but it had been stopped before the thrombotic event leading to the recurrent pulmonary embolism. The formation of the thrombi had probably been caused by the migration of the filter and the subsequent perforation, which may have been facilitated by the cessation of the anticoagulation. PMID- 2269717 TI - Dopamine dependence in hypocalcemic patients. AB - Two patients admitted for decompensated chronic obstructive pulmonary disease developed arterial hypotension requiring the prolonged infusion of dopamine. They had no sign of acute circulatory failure and their blood lactate levels were normal. In the two patients, the correction of unsuspected hypocalcemia allowed the rapid discontinuation of the dopamine infusion. PMID- 2269716 TI - Intensive care management of Guillain-Barre syndrome during pregnancy. AB - A particularly severe case of Guillain-Barre syndrome occurring during pregnancy is reported. The therapeutic approach including plasmapheresis, ventilation, analgesia, sedation, metabolic requirements and heparin therapy is discussed with the consequences on foetal development and the early days of life. PMID- 2269718 TI - Cardiac asthma presenting as status asthmaticus: deleterious effect of epinephrine therapy. AB - Epinephrine is a potent bronchodilator currently used to treat severe asthma, although there is no proven advantage of this drug over beta 2 adrenergic agonists. By contrast, as demonstrated here, the use of such a potent vasoconstrictor can worsen hemodynamic status when left ventricular dysfunction is associated with asthma or is the cause for dyspnea. We describe the case of a 60-year-old man with an history of chronic asthmatic bronchitis admitted for status asthmaticus. Bronchodilator therapy, including high dosages of intravenous epinephrine, failed to improve the patient and he was intubated and mechanically ventilated. Several hours later, a right heart catheterization revealed severe unexpected left heart dysfunction with a capillary wedge pressure of 45 mmHg and a cardiac index of 1.7 l/min/m2. Epinephrine was gradually stopped which resulted in a decrease in mean arterial blood pressure and an improvement of hemodynamic status. He was discharged on home mechanical ventilation. In this patient, ischemic left heart failure was revealed by a clinical picture mimicking status asthmaticus. Epinephrine, given as bronchodilator therapy on an empiric basis precipitated the patient into cardiogenic shock. Therefore this drug should not be recommended in face of the possibility of cardiac asthma or associated cardiac dysfunction. PMID- 2269719 TI - Successful diaphragmatic pacing for idiopathic alveolar hypoventilation. AB - We describe the case of a 17-year-old woman noted to have idiopathic alveolar hypoventilation, with multiple Intensive Care Unit (ICU) admissions because of acute respiratory failure (ARF) due to respiratory infections. After two years of diaphragmatic pacing arterial blood gases have substantially improved, without obstructive apnoea. Signs of right ventricular enlargement and pulmonary hypertension have decreased. Morning headache and diurnal somnolence have disappeared, and she is also able to perform more physical and mental activity, allowing her to enjoy a better quality of life. PMID- 2269720 TI - Sir Robert Macintosh and intensive care. PMID- 2269721 TI - Development of intensive therapy. A UK view for the future. PMID- 2269722 TI - Thresholds for transient cavitation produced by pulsed ultrasound in a controlled nuclei environment. AB - Transient cavitation is a discrete phenomenon that relies on the existence of stabilized nuclei, or pockets of gas within a host fluid, for its genesis. A convenient descriptor for assessing the likelihood of transient cavitation is the threshold pressure, or the minimum acoustic pressure necessary to initiate bubble growth and subsequent collapse. An automated experimental apparatus has been developed to determine thresholds for cavitation produced in a fluid by short tone bursts of ultrasound at 0.76, 0.99, and 2.30 MHz. A fluid jet was used to convect potential cavitation nuclei through the focal region of the insonifying transducer. Potential nuclei tested include 1-microns polystyrene spheres, microbubbles in the 1- to 10-microns range that are stabilized with human serum albumin, and whole blood constituents. Cavitation was detected by a passive acoustical technique that is sensitive to sound scattered from cavitation bubbles. Measurements of the transient cavitation threshold in water, in a fluid of higher viscosity, and in diluted whole blood are presented. These experimental measurements of cavitation thresholds elucidate the importance of ultrasound, host fluid, and nuclei parameters in determining these thresholds. These results are interpreted in the context of an approximate analytical theory for the prediction of the onset of cavitation. PMID- 2269723 TI - Acoustic cues for consonant identification by patients who use the Ineraid cochlear implant. AB - Ten patients who use the Ineraid cochlear implant were tested on a consonant identification task. The stimuli were 16 consonants in the "aCa" environment. The patients who scored greater than 60 percent correct were found to have high feature information scores for amplitude envelope features and for features requiring the detection of high-frequency energy. The patients who scored less than 60 percent correct exhibited lower scores for all features of the signal. The difference in performance between the two groups of patients may be due, at least in part, to differences in the detection or resolution of high-frequency components in the speech signal. PMID- 2269724 TI - Stimulus order effects in vowel discrimination. AB - In same-different discrimination tasks employing isolated vowel sounds, subjects often give significantly more "different" responses to one order of two stimuli than to the other order. Cowan and Morse [J. Acoust. Soc. Am. 79, 500-507 (1986)] proposed a neutralization hypothesis to account for such effects: The first vowel in a pair is assumed to change its quality in memory in the direction of the neutral vowel, schwa. Three experiments were conducted using a variety of vowels and some initial support for the hypothesis was obtained, using a large stimulus set, but conflicting evidence with smaller stimulus sets. Rather than becoming more similar to schwa, the first vowel in a pair seems to drift toward the interior of the stimulus range employed in a given test. Several possible explanations are discussed for this tendency and its relation to presentation order effects obtained in other psychophysical paradigms is noted. PMID- 2269725 TI - Vowel amplitude variation associated with the heart cycle. AB - Modulation of the acoustic amplitude of a sustained vowel across the cardiac (ECG) cycle was examined by signal-averaging techniques. Ten normal men prolonged [a] at a comfortable Fo maintained within three SPL ranges: 60-68, 70-78, and 80 88 dB. Peak-to-peak amplitude variation associated with the heart cycle averaged 8.5% (s.d. = 5.4) re: mean, varying from about 14% at low SPLs to approximately 3% at high SPLs. The amplitude modulation was estimated to account for 11.8% of the measured short-term amplitude perturbation (shimmer), ranging from about 5% to almost 22% for individual samples. The mean deterministic shimmer (Sd) was 0.036 dB (s.d. = 0.019), with a trend toward decreasing Sd with increasing SPL. Additionally, fundamental frequency variation across the heart cycle within these phonations was comparable to that observed by Orlikoff and Baken [J. Acoust. Soc. Am. 85, 888-893 (1989)], and was shown to be uninfluenced by vocal SPL, although deterministic jitter (Jd) did decrease with vocal intensity. The results are discussed in terms of how the phonovascular relationship may affect the reliability and interpretation of acoustic shimmer measures. PMID- 2269727 TI - The effects of bandwidth on the detectability of narrow- and wideband signals. AB - The effects of masker bandwidth on the detection of narrow- and wideband signals have been investigated. For both kinds of signals, plots of threshold as a function of masker bandwidth yielded by both narrow- and wideband signals are reasonably described with two intersecting lines. Threshold initially increase with masker bandwidth and then become independent of further increases. The rate of increase depends on the signal spectrum. The bandwidth at which the lines intersect varies with signal bandwidth and also mode of masker presentation (i.e., whether the masker is gated with the signal or is present continuously). Internal filtering is most accurate when the masker is present continuously. A model is proposed in which a listener's decisions about the presence of narrow band signals are based upon estimates of stimulus energy within a critical band. These estimates are degraded by bandwidth-dependent processing errors. When the signal to be detected spans several critical bands (i.e., is wideband), the model forms a test statistic by summing the outputs of the relevant critical bands. The model permits the contribution of each band to the sum to vary with masker bandwidth because it incorporates a form of lateral suppression. Thresholds of narrow-band signals in gated maskers and wideband signals in gated and continuous maskers are predicted by the model. However, the model fails to account for the detectability of narrow-band signals in continuous maskers. PMID- 2269726 TI - Effects of postlingual deafness on speech production: implications for the role of auditory feedback. AB - This study investigated some effects of postlingual deafness on speech by exploring selected properties of consonants, vowels, and suprasegmentals in the speech of seven totally, postlingually deafened individuals. The observed speech properties included parameters that function as phonological contrasts in English, as well as parameters that constitute primarily phonetic distinctions. The results demonstrated that postlingual deafness affects the production of all classes of speech sounds, suggesting that auditory feedback is implicated in regulating the phonetic precision of consonants, vowels, and suprasegmentals over the long term. In addition, the results are discussed in relation to factors that may influence the degree of speech impairment, such as age at onset of deafness. PMID- 2269728 TI - Harmonic and melodic octave templates. AB - For normal-hearing adult listeners, two simultaneous pure tones with a frequency ratio close to 2/1 may perceptually fuse into a single sound, which shows that such listeners are sensitive to "octave harmony." Many adult listeners are also able to consistently adjust two successive pure tones "one octave apart," which shows that they possess melodic octave templates. According to Terhardt [J. Acoust. Soc. Am. 55, 1061-1069 (1974)], melodic octave templates and the perception of octave harmony originate from a common learning process taking place in early life. In the two experiments reported here, subjects performed repeated octave adjustments for pairs of simultaneous and successive tone bursts. Both tones were presented monaurally, at 45 or 65 dB SPL. The frequency of the lower tone (fref) was an independent variable, while the frequency of the higher tone was adjustable within a 500-cent range. In some conditions, when the two tones were presented simultaneously, they were sinusoidally frequency modulated in a coherent manner, at a rate of 2 or 4 Hz; the aim of this frequency modulation was to force the subjects to adopt a synthetic listening strategy, i.e., to base their adjustments on perceived harmony. For fref values ranging from 270-2000 Hz, subjects performed consistent adjustments when the tones were presented successively: fref had little effect on the adjustments' variability. However, in the same frequency range, the variability of the harmonic adjustments markedly increased with fref; for the highest fref values, it was much greater than the variability of the melodic adjustments. The results suggest that, in adult listeners, the perception of octave harmony disappears at frequencies for which melodic octaves are still accurately perceived. PMID- 2269729 TI - The loudness of sounds that increase and decrease continuously in level. AB - A sound at a low level is heard as much softer after having decreased continuously from higher levels than if presented after a period of silence at that same low level. Canevet [Acustica 61, 256-264 (1986)] demonstrated this phenomenon for a tone that (1) decreased from 65 to 20 dB in 180 s; he also presented a tone that (2) increased from 20 dB, or (3) was presented as pairs of bursts at various levels in random order. Below about 40 dB, loudness changed most rapidly in the decreasing condition so that, at 20 dB, the tone was judged ten times softer than in conditions (2) and (3). In the present experiments, magnitude estimation was used to examine the possible role of judgmental biases and adaptation in this rapid loudness decline, which we call decruitment. Results show that decruitment did not come about because subjects made many successive loudness judgments; loudness declined as much when a tone was judged only twice, at the beginning and end of its 180-s decrease. In contrast, interrupting the decreasing tone so that it was heard only at 70 dB and 160 s later at 30 dB greatly diminished the decruitment. Similarly, pairs of 500-ms tone bursts presented at successively lower levels instead of continously decreasing did not show decruitment, suggesting that sequential biases are irrelevant. The likely cause of decruitment is sensory adaptation. PMID- 2269730 TI - Effects of stimulus level on forward-masked psychophysical tuning curves in quiet and in noise. AB - Forward-masked psychophysical tuning curves were obtained from normal-hearing listeners at different probe levels in quiet and in a broadband background noise. In quiet, tuning-curve shape changed with probe level. For six listeners, tuning curves became broader with increasing probe level, primarily due to a decrease in the low-frequency slopes. For one listener, tuning curves became narrower with increasing probe level. The addition of a background noise, which was presented continuously at a level 10 dB below the noise level required to mask the probe tone, reduced the masker levels required to mask the probe tone. The reduction was greater near the tip of the tuning curve than on the tail, so that tuning curves in background noise were narrower than those obtained in quiet. Tuning curves with comparable masker levels near the tip of the tuning curve (Lmtip) were similar in shape, regardless of probe level or whether tuning curves were obtained in quiet or noise. Comparisons of tuning-curve characteristics derived by fitting tuning curves with least-squares procedures, indicated that low frequency slopes decreased with Lmtip. As a consequence, Q10 dB values decreased with Lmtip. These results are consistent with the interpretation that tuning curve shapes are determined by the intensities of the maskers required to mask the probe tone. The addition of a background noise restricted (partially masked) the excitation pattern of the probe so that lower masker intensities were required to "forward mask" the probe tone, and narrower tuning curves resulted from less intense markers. The results are well described by a two-process model of auditory excitation patterns. PMID- 2269731 TI - Frequency discrimination in the monkey. AB - This study evaluated frequency discrimination ability in 11 monkeys over an extended period of time using a repeating-standard procedure and the method of constant stimuli. The intersubject variability of the difference limens for frequency (delta F) was large, as reported by other investigators, but similar in magnitude to the variability of the difference limens for intensity (delta I) from three of the same subjects in an intensity discrimination experiment. Continued training generally resulted in a rapid decrease in delta F's, followed by a longer-term, slower decrease. For one subject delta F's slowly decreased throughout a 190-week time period. This long-term training effect was specific to frequency discrimination; a similar effect was not observed for the same subject tested in an intensity discrimination experiment. Finally, delta F's from the well-trained monkeys of this study were larger than monkey delta F's from this laboratory reported in an earlier study, and than human delta F's. An anatomical explanation for the human/monkey delta F magnitude difference is explored. PMID- 2269732 TI - The combination of interaural information across frequencies: lateralization on the basis of interaural delay. AB - Three experiments were carried out that employed low-frequency tone complexes with interaural delays that varied across the frequency domain. In the first experiment, threshold interaural delays were measured for three-tone complexes for which one, two, or all three components were delayed. The center frequency was 750 Hz and the frequency spacing (delta f) between components was 20, 50, 100, 250, or 450 Hz. For all delta f's, the presence of two diotic components elevated the threshold interaural delays obtained for the third component relative to that obtained for a pure tone of the same frequency. In the second experiment, observers made left-right judgments regarding the direction of movement of signals for which two components were delayed by 25 microseconds to the left ear during one interval and to the right ear during the other interval, while a third component of a variable time difference was delayed to the opposite side as the tone pair. Subjects reported single intracranial images during each interval, and the data showed that interaural delays of one component to one ear could be offset by interaural delays of the other two components to the other ear. In the final experiment, threshold interaural delays were measured for five tone complexes in which one, two, three, four, or five components were delayed. The center frequency was 750 Hz and delta f was fixed at 100 Hz. Thresholds decreased in a linear fashion as the number of delayed components increased, falling by about a factor of 5 as the number of delayed components went from one to five. These results are consistent with spectrally synthetic binaural processing, with the lateral position of intracranial images determined by a combination of interaural information across the spectrum. These effects could be brought about by a linear combination of the outputs of frequency-specific cross correlation networks or by a wideband cross correlation of the signals at the two ears. PMID- 2269733 TI - Classification of audiograms by sequential testing using a dynamic Bayesian procedure. AB - A new method for estimating audiograms using behavioral responses is presented. The method is based upon a modification of the Bayesian probability formula in which an outcome is predicted from a static set of events. In the new method, classification of audiograms by sequential testing (CAST), the probabilities of occurrence of audiogram patterns are dynamically updated according to the outcome of each test trial. Computer simulation using an infant response model suggests that the procedure is efficient, sensitive, and specific. PMID- 2269734 TI - The auditory periphery of the ferret. I: Directional response properties and the pattern of interaural level differences. AB - The transformations of sound by the auditory periphery of the ferret have been investigated using an impulse response technique for a large number of sound locations surrounding the animal. Individual frequencies were extracted from the detailed spectral transformation functions (STFs) obtained for each stimulus location and, using sophisticated spatial interpolation routines, were used to calculate the directional response of the periphery at that frequency. The strength of the directional response was directly related to the analysis frequency. Furthermore, as the analysis frequency was increased to 20 kHz, the orientation of the directional response increased in elevation from the horizon (E0 degrees) to about E30 degrees, while the azimuthal location remained fairly constant at 30 degrees to 40 degrees from the midline. For analysis frequencies above 20 kHz, the response became increasingly directional toward the ipsilateral interaural axis. The interaural level differences (ILDs) were also calculated for all animals studied. ILDs increased from around 5 to 25 dB over the range of frequencies from 3-24 kHz. The two-dimensional patterns of iso-ILD contours were roughly concentric and centered on the interaural axis for frequencies below 16 kHz. For higher frequencies, there was a tendency for the ILD contours to be centered on more anterior and inferior locations. The increased directionality of the auditory periphery with increasing analysis frequency, together with the presence of sharp nulls in the response at high analysis frequencies, is consistent with a diffractive effect produced by the aperture of the pinna. However, this simple model does not predict the directional responses over the low to middle frequency range. PMID- 2269735 TI - The auditory periphery of the ferret. II: The spectral transformations of the external ear and their implications for sound localization. AB - In the previous paper the directional response characteristics of the ferret auditory periphery were examined. In this study further measurements of the spectral transfer functions (STFs) of the auditory periphery were obtained at locations close to the tympanic membrane. There was considerable variation in the STFs recorded from different animals and between recordings made at each end of the auditory canal in the same animal. However, calculation of the so called "location dependency function" demonstrated that changes in the location of the stimulus produced the same pattern of changes in the STFs in all recordings. Changes in the spectral transformation for azimuth locations in the ipsilateral auditory field were examined by calculating the horizon STF. The gain transformations of frequencies below 20 kHz were found to be asymmetrical about the interaural axis so that maximum gain was obtained for anterior stimulus locations. In contrast, the maximum gain for frequencies above 20 kHz was obtained for stimulus locations about the interaural axis, and movement of the stimulus location into either the anterior or posterior fields produced symmetrical reductions in gain. These changes were related to the directional properties of the periphery examined in the previous paper [S. Carlile, J. Acoust. Soc. Am. 88, 2180-2195 (1990)]. The spatial resolution of the monaural information provided by the peripheral STFs is dependent on the rate of change of the transformations as a function of azimuthal displacement of the stimulus location. This was examined by calculating the unsigned first spatial derivative for each frequency in the horizon STF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269736 TI - Electrically evoked whole-nerve action potentials: parametric data from the cat. AB - In a companion paper [Brown et al., J. Acoust. Soc. Am. 88, 1385-1391 (1990)], a method for recording the electrically evoked whole-nerve action potential in human cochlear implant users was reported. The procedure for recording the response requires that two biphasic current pulses, a "masker" and a "probe," be presented at a rate and level sufficient to drive the auditory nerve into a refractory state. The present study was designed to assess the sensitivity of that recording technique to variations in stimulation parameters. The experiments described in this paper demonstrate that: (1) the EAP as recorded in the cat is triphasic and is defined by two negative peaks occurring at latencies of approximately 0.26 and 0.82 ms; (2) EAP amplitude is independent of the level of the masker stimulus for current levels equal to or greater than the current level of the probe stimulus; and (3) the time course of recovery of the EAP from the refractory state is stable over a range of both probe and masker current levels. PMID- 2269737 TI - Response of auditory-nerve fibers to intensity increments in a multitone complex: neural correlates of profile analysis. AB - Recent psychophysical studies have shown that the detection of an intensity increment superimposed on the center component (1 kHz) of a multitone complex (1, 3, 7, or 11 components) improves as more components are added outside of the critical band. It has been suggested that this form of intensity discrimination is based on a change in the neural profile. To test this hypothesis, neural profiles were constructed by plotting the degree of phase locking to the 1-kHz tone as a function of each unit's characteristic frequency (CF). Neural phase locking profile to the 1-component signal at 1 kHz had a broad peak; however, the neural profile became narrower as the number of components in the signal increased. The just detectable increment for the 1-component condition was -5 dB re: 1000-Hz component level (3.86-dB increment plus component level re: component level), whereas, for the 3-, 7-, and 11-component conditions, it was -15 dB re: component level (1.42 dB). The neural and psychophysical IDL for the chinchilla were similar for the 1-component condition. However, the overall trends in the psychophysical and neural data are different. In the psychophysical studies IDL is typically poorest in the 3-component condition and improves when more components are added. By contrast, the neural IDL was poorest in the 1-component condition and improved when more components were added. In the multicomponent conditions, units with CFs in 492-1380 Hz were found to be more sensitive in detecting the intensity increment to the 1000-Hz component. PMID- 2269738 TI - Stimulus dependencies of the gerbil brain-stem auditory-evoked response (BAER). III: Additivity of click level and rate with noise level. AB - Two experiments were performed that evaluated the effects of ipsilateral-direct broadband noise maskers on the gerbil brain-stem auditory-evoked response (BAER) to click stimuli. In experiment 1, clicks were presented at 27 Hz at levels including 70, 80, 90, and 100 dB pSPL. Noise conditions included a no-noise control, and included noise levels varying in 10-dB increments from 20 dB SPL to a maximum noise level of 50, 60, 70, and 80 dB SPL for click levels of 70, 80, 90, and 100 dB pSPL, respectively. Gerbil BAER peaks were labeled with small roman numerals to distinguish them from human BAER peaks. The dependent variables included waves i and v latencies and amplitudes. Peak latencies increased and peak amplitudes decreased with decreasing click level and increasing noise level. To a first approximation, peak latencies and amplitudes showed changes with increasing noise level that were similar across click level. With increasing click level, there was little or no effect on the i-v interval. There was an increase in the i-v interval with increasing noise level. In experiment 2, click level was held constant at 90 dB pSPL, and click rates included 15, 40, 65, and 90 Hz. For each click rate, noise conditions included a no-noise control, and noise levels included 20, 30, 40, 50, 60, and 70 dB SPL. With increasing click rate and noise level, there was an increase in peak latencies, an increase in the i-v interval, and a decrease in peak amplitudes. The magnitude of peak latency and amplitude shifts with increasing click rate was dependent on noise level. Specifically, the magnitude of rate-dependent changes decreased with increasing level of broadband noise. These data are compared to human BAER experiments, and are found to be in fundamental agreement. PMID- 2269739 TI - Three-dimensional numerical modeling of geoacoustic scattering from seafloor topography. AB - A three-dimensional (3-D), second-order finite-difference method was used to create synthetic seismograms for wave propagation in heterogeneous media in order to investigate the scattering of elastic and acoustic energy due to topography on the seafloor. The method uses a fully staggered grid in Cartesian coordinates as developed by Virieux [Geophysics 51, 889-901 (1986)]. Numerical results were generated for two models: a linear fault scarp on the seafloor, and a flat seafloor containing a rectangular channel. Wave-front snapshots allow the scattering and focusing of different wave modes with direction to be visualized. Compressional and shear wave backscattering from the sides of the features can be seen together with the trapped compressional wave energy propagating inside the channel. The results illustrate the effects of out of the plane scattering due to simple seafloor topographic features. PMID- 2269740 TI - Characterization of measurement system effects in ultrasonic scattering experiments. AB - A general model is developed to characterize the effect of an ultrasonic measurement system on the experimental determination of ultrasonic scattering as a function of angle and frequency. The model includes arbitrary emitter beams and detector apertures as angular spectra of plane waves. Arbitrary emitted pulses and detector time gates are incorporated through frequency spectra of temporal harmonics. A transformation of variables is employed to express the spectrum of the measured pressure as a product in wave space of a system function and the Fourier transform of the medium variations. The mean-square value of the measured pressure spectrum is similarly expressed as a product of the squared magnitude of the system function and the power spectrum of the medium variations. The measured quantities are shown to become scaled values of intrinsic scattering characteristics when the system function weight is concentrated relative to the medium characteristics in wave space. The assumption of an indefinitely long detector gate is used to represent the system function as a product in which one factor is a beam function dependent on spatial frequency and the other factors are dependent on temporal frequency. Beam-function calculations as well as calculations of second moments and overall beam weight are made for identical Gaussian-shaped emitter and detector apertures to illustrate the blurring and weighting effects of measurement system beam patterns as a function of scattering angle. The moment calculations are shown to identify circumstances when the medium variation function can be factored out from under the integral and the measurement represented as a simple product of the medium properties and a measurement system weight. The results may be used to design scattering experiments in which degradations due to system effects are within acceptable limits. PMID- 2269741 TI - Transient wave response of the violin body. PMID- 2269742 TI - Regression equations for the transfer functions of ANSI S3.5-1969. PMID- 2269743 TI - Alternate focusing fluids for passive acoustic targets. PMID- 2269744 TI - Elsie Stephenson: Britain's nursing Messiah of the twentieth century. PMID- 2269745 TI - Empathy, experience of burnout and attitudes towards demented patients among nursing staff in geriatric care. AB - A non-anonymous questionnaire was distributed to all nursing staff (n = 557) including RNs, LPNs (psychiatric), LPNs (somatic) and nurses' aides, in one nursing home, one somatic long-term care clinic and one psychogeriatric clinic. Scales measuring empathy, burnout experience and attitudes towards demented patients were included in the questionnaire. The aim of the study was to compare levels of empathy, burnout experience and attitudes among different categories of nursing staff and to examine connections between empathy, burnout and attitudes. The nursing staff showed an overall figure of moderately well-developed empathy and the RNs showed the highest empathy. The RNs had a significantly lower degree of burnout compared to the nurses' aides and the LPNs. Of all respondents, 27.4% were assessed at risk from burnout. Overall, the staff showed a moderately positive attitude towards demented patients and the RNs were most positive. No linear correlation was found between empathy, burnout experience and attitudes. However, a weak negative correlation between burnout and empathy is in accordance with other authors who are suggesting that burnout experience leads to lower empathy in the nursing staff. The fact that the RNs showed the most positive attitudes towards demented patients and had the highest level of empathy compared to LPNs and nurses' aides could be related to lower degree of burnout assessed in the RNs. Qualitative and quantitative overload among the LPNs and nurses' aides connected to the growing number of demented patients in the institutions examined are discussed. PMID- 2269746 TI - Aspects of communication with people who have attempted suicide. AB - This paper addresses some potential difficulties in communication which may occur between health-care professionals and those who are being assessed following an unsuccessful suicide attempt. Attitudes towards suicide and attempted suicide which may be held by the patient and carer are reviewed and the effects that these may have on communication, particularly at the assessment stage, are considered. Some techniques to enhance communication and assessment are proposed. PMID- 2269747 TI - Fostering hope in terminally-ill people. AB - This study explored the meaning of hope and identified strategies that are used to foster hope in a convenience sample of 30 terminally-ill adults using the technique of methodological triangulation (interview, Herth Hope Index and Background Data Form). Cross-sectional data were collected on 20 of the subjects, and longitudinal data were collected on 10 of the subjects in order to provide a clearer understanding of the hoping process during the dying trajectory. Hope was defined as an inner power directed toward enrichment of 'being'. With the exception of those diagnosed with AIDS, overall hope levels among subjects were high and were found to remain stable over time and across the background variables. Seven hope-fostering categories and three hope-hindering categories were identified based on the interview responses. The findings could serve as a guide for the development of interventions to foster hope in terminally-ill people. PMID- 2269748 TI - Measuring the quality of nursing care: a consideration of different approaches. AB - This paper argues that a preoccupation with cost-effectiveness threatens to swamp nurses' traditional concern with quality of care, and underlines the importance of clinical nurses becoming familiar with the complexities of quality measurement. Terminology widely used in the nursing literature is clarified and research studies that address the quality of nursing care are reviewed. It is suggested that whilst some of these have provided important theoretical insights into quality issues, the qualitative research methods employed have so far failed to provide a practical alternative to the more 'objective' measures of quality currently adopted by clinical nurses and their managers. Generic measures of quality are identified and categorized and it is suggested that most of these are in need of extensive validity testing in relation to the concepts of quality that they purport to measure. The measures of quality themselves may be less important than the content in and process by which they are applied. 'Top-down' and 'bottom up' approaches to measurement are discussed in relation to the notion of facilitative leadership. The value of top-down approaches is questioned on the grounds that they may violate the integrity of the quality-assurance cycle and prevent clinical nurses from making the commitment that is necessary in order to assess and improve the quality of their nursing practice. PMID- 2269749 TI - The utilization of research findings in clinical nursing practice. AB - This paper considers the issue of utilizing research findings in nursing practice. It covers the justification for utilizing research in practice, and whether research is actually implemented. Previous studies focusing upon the process of utilizing research are analysed, and consideration is given to how research should be evaluated and implemented and the factors affecting this. The literature reviewed demonstrates that the implementation of research in clinical practice is a complex operation. Attempts to achieve research-based practice need to be well thought through and organized, with those involved at all levels being interested and committed to its success. PMID- 2269750 TI - Focus group interview: a research technique for informed nursing practice. AB - AIDS has become a leading cause of death for women between the ages of 25 and 34. An overwhelming proportion of these women are Black (52%) or Hispanic (20%). Despite the disproportionate number of minority women who are HIV infected, the majority of AIDS educational programmes have been directed at the White gay male. The purpose of this paper is to present a qualitative research technique which used focus group interviews to promote the development of a programme devised to reduce risk behaviours in minority populations. A summary of the investigation and implications for nursing are also presented. PMID- 2269751 TI - Restructuring: an emerging theory on the process of losing weight. AB - A qualitative research design (grounded theory) was used to analyse the experiences of dieters attending a weight loss programme. Two hundred hours of observations at a nationally known weight reduction centre, a review of selected documents from the organization and multiple in-depth interviews with 13 informants were the data sources for this study. Data generation took place over a 21-month period. A substantive theory of restructuring identified three stages in the process of losing weight. These stages and key elements of the weight loss process are presented. PMID- 2269752 TI - The costing of nursing care: a study of 65 colorectal cancer patients. AB - Nursing care is a major factor in the cost of most medical treatments. This paper reports on two alternative techniques for estimating the costs of nursing care, in the context of colorectal cancer treatment on a surgical ward in the University Hospital, Nottingham. The simpler, but cruder, technique is based on average patient costs, whilst the other is patient-specific and incorporates the use of nursing dependency data. Results from the two estimation methods are compared and the implications for the proper costing of nursing care are discussed. PMID- 2269753 TI - Need and provision of health visiting in the London district health authorities. AB - This paper considers the degree of equity associated with the delivery of health visiting in London, England. As is common in the National Health Service, it is argued that an area with a greater need for a service should get greater provision of that service. Different indices for measuring needs and resources are discussed. In particular, the vital distinction between measures of resource input and output is examined. The relationships between provision indices are discussed and then the associations between need and provision are examined. It is concluded that the implications for equity are unclear, as the magnitude of the correlations change depending on the choice of indices. PMID- 2269754 TI - An experiment in psychiatric community care in north Staffordshire: the experience of working with relatives of mentally-ill people. AB - This paper describes the changing nature of the relationship between the consumers and providers of services, following the transition from a hospital to a community-based service. One aspect of this change, the development of a relatives' group, is considered in more detail. Those attitudes and approaches which help or hinder staff working with relatives are discussed. PMID- 2269755 TI - The perception of psychiatric-hospital ward sisters/charge nurses towards nursing models. AB - A search of the literature revealed a dearth of research on hospital ward-based practitioners' opinions/perceptions towards nursing models. This is surprising considering that such frameworks are being introduced into patient care settings on an international basis. As part of a larger investigation pertaining to model selection, the researcher interviewed a population of 95 ward managers, giving each of them the opportunity to put forward their views concerning models of nursing. The research area was psychiatric continuing-care/rehabilitation facilities in Northern Ireland. The majority of opinions (61.1%) were positive in nature while 23.2% of respondents voiced negative perceptions. Implications for nursing practice, education and administration are raised from the study's findings. PMID- 2269756 TI - Nursing education leadership. Effect of situational and constraint variables on leadership style. AB - A descriptive study investigating the effect of situational and constraint variables on leadership style is reported. A sample of 35 administrators of college (diploma) nursing programmes and 106 of their senior faculty participated in the study. The Leadership Style Analysis Instrument was used to determine the administrators' leadership styles, as perceived by the administrators themselves and by their senior faculty. Demographic characteristics of the administrators and constraint variables were examined by chi-square analysis (0.05) regarding their relationship to leadership styles. It was found that despite variations in administrator characteristics and extent of constraints, the perceived leadership style was consistently relationship-oriented. The results have implications for educators and administrators in nursing. PMID- 2269757 TI - Power for nursing education. AB - The topic of power and politics is a recurrent theme in the nursing literature, but not, I wish to suggest, in the nursing educational literature. This paper introduces the topic of power as a nursing educational issue. It is divided into three sections: (a) what a concept of power might mean for nursing education; (b) the nature and form of power relationships within nursing education; and (c) the nature, form and efficacy of the current professional strategies to gain power. First, two definitions of power for nursing education are explored: (a) the power inherent in organizational structures; and (b) the notion of practising nursing education as an empowering profession. Next, a theoretical framework is applied to specific examples of power relationships within nursing education. Two views of power and their inter-relationship with decision-making in curriculum matters are described: 'overt conflict' and 'control of the institution's agenda'. It is argued that these still fail to pick up important instances of the strategies to gain power. Finally, examples of strategies used to gain power in colleges of nursing are made explicit. Concurrently, questions are raised in relation to their efficacy and alternative strategies more congruent with the role of professional educator are advocated. It is argued that nursing education's most lasting form of power will rest in the development of pedagogical knowledge expertise and a research basis: in essence, the development of an academic identity in nursing education. PMID- 2269758 TI - Smoking habits of nurses and midwives. AB - A study was designed to examine the hypothesis that increased awareness of the health hazards of smoking aids smoking cessation in female health care workers. One hundred and thirteen nurses and midwives completed a questionnaire about their smoking habits. When the group was tested as a whole against the national average for the same socio-economic group, it was found that there was a strong similarity between the subject's smoking habits and the national average. However, when the nurses and midwives were separated into two groups, the nurses smoked significantly more than the national average, whereas the midwives smoked significantly less. In addition, there was an intriguing finding that a highly significant number of the midwives had never smoked compared to the national average. PMID- 2269759 TI - Free Paps needed. PMID- 2269761 TI - Animal research: pro and con. PMID- 2269760 TI - An incest survivor speaks. PMID- 2269762 TI - AMWA: a voice for women in medicine. PMID- 2269763 TI - The history of students in AMWA. PMID- 2269764 TI - The American Medical Women's Association and the role of the woman physician, 1915-1990. PMID- 2269765 TI - Separate but integrated: Bertha Van Hoosen and the founding of AMWA. PMID- 2269766 TI - Respected by all . . . in all times: the AMWA presidents. PMID- 2269767 TI - The AMWA Archives. PMID- 2269768 TI - Looking back at progress: AMWA award winners. PMID- 2269769 TI - Hypoplasia of the humeral trochlea. AB - Radiographic studies of three cases of hypoplasia of the humeral trochlea were done. Several other anomalies were also detected, including a hypoplastic capitellum in case 2, a hyperplastic radial head in cases 2 and 3, and bulging of the loose joint capsule in case 3. Operations in cases 1 and 3, disclosed that ganglions and fibrous septa compressed the ulnar nerve. The cause of ulnar nerve palsy in patients with hypoplasia of the humeral trochlea is thought to be associated with the high incidence of ganglions in hypoplastic elbow joints. The ganglion may play a role. PMID- 2269770 TI - A noninvasive technique for diagnosis of chronic compartment syndrome in the first dorsal interosseous muscle. PMID- 2269771 TI - A standardized measurement of ulnar carpal translocation. PMID- 2269772 TI - The palmar radiocarpal ligaments: a study of adult and fetal human wrist joints. AB - The palmar radiocarpal ligaments were studied with use of fifty-four dissected adult cadaver wrists and serial sections on twenty-three wrists from fetuses ranging in size from 23 to 230 millimeters crown-rump length. Three palmar radiocarpal ligaments were clearly identified: the radioscaphocapitate, long radiolunate, and short radiolunate ligaments. The radioscaphocapitate ligament originates from the radial styloid process and inserts into the radial aspect of the waist of the scaphoid, hemicircumferentially around the distal pole of the scaphoid and interdigitates with fibers from the palmar aspect of the triangular fibrocartilage complex just palmar to the head of the capitate, with only a minor insertion distally into the body of the capitate. The long radiolunate ligament originates just ulnar to the radioscaphocapitate ligament, being separated from it throughout its course by the interligamentous sulcus. The long radiolunate supports, but is separate from, the palmar aspect of the scapholunate interosseous ligament, and inserts into the radial half of the palmar surface of the lunate. The short radiolunate ligament, previously not described, originates just palmar to the lunate facet of the distal radius articular surface and inserts as a flat sheet of fibers into the proximal margin of the palmar surface of the lunate. Each ligament is intracapsular, enveloped within a continuous superficial fibrous stratum and deep synovial stratum. PMID- 2269773 TI - Radiographic analysis of selective ligament sectioning at the carpal scaphoid: a cadaver study. AB - Although scapholunate diastasis with rotatory subluxation of the scaphoid (stage I perilunar instability determined by Mayfield's classification) has been studied by several investigators, the exact contribution of the supporting ligaments is still being defined. We designed and executed an experimental study using six fresh-frozen cadaver specimens to demonstrate the radiographic changes seen on standard and stress wrist radiographs that correlate with the sequential sectioning of the scapholunate stabilizing ligaments. The radioscapho-lunate ligament, the palmar scapholunate interosseous ligament, the dorsal scapholunate interosseous ligament, and the radiocapitate ligament were sectioned sequentially to simulate a progressive wrist injury caused by an extension, intercarpal supination and ulnar deviation force. The results showed significant ligamentous injury must occur before commonly used radiographic limits are exceeded. The lateral scapholunate angle most closely reflected the progressive nature of this injury. PMID- 2269774 TI - Experimental corrective scaphoid osteotomy for scaphoid malunion with abnormal wrist mechanics. AB - Two cases of painful posttraumatic scaphoid malunion (hump-back deformity) associated with dorsal intercalated segmental instability deformity and limitation of wrist motion are presented. Carpal alignment and wrist motion improved after an experimental opening wedge scaphoid osteotomy with iliac bone graft and Herbert screw fixation. The scaphoid deformities (angulation and shortening) were effectively corrected. PMID- 2269775 TI - Congenital bipartite scaphoid. AB - A case of bilateral congenital bipartite scaphoid followed from early ossification of the scaphoid to skeletal maturity is presented. Magnetic resonance imaging was shown to be helpful in differentiating this condition from traumatic pseudarthrosis of the scaphoid. The history of this rare anomaly is discussed. PMID- 2269776 TI - Dorsal dislocation of the trapezoid. AB - A case of dorsal dislocation of the trapezoid associated with dorsal subluxation of the carpometacarpal joints of the index and long fingers is described. The initial trapezoid subluxation was overlooked and it progressed quickly to a complete dislocation. Open reduction and capsular repair without internal fixation was followed by early recurrent trapezoid subluxation. Repeat open reduction combined with a limited intercarpal arthrodesis was used as a salvage procedure and produced a good result. PMID- 2269777 TI - Histologic and magnetic resonance imaging correlations in Kienbock's disease. AB - Nine patients had magnetic resonance imaging studies to aid in the diagnosis of wrist pain in the midcarpal region. Six had positive magnetic resonance imaging studies with a decrease in signal intensity from the area of the lunate, one had an occult ganglion, and two had negative studies. Among the six patients with a diagnosis of Kienbock's disease by magnetic resonance imaging, four patients had collapse of the lunate on plain radiographs, and the other two patients had normal wrist radiographs. Magnetic resonance imaging studies showed a substantial decrease in the signal intensity on T1- and T2-weighted images of the entire lunate in three patients, and three patients had focal areas of decreased signal intensity. All of the patients had a biopsy of the lunate at the time of surgery. The histology of the biopsies of the lunate appeared to correspond to the magnetic resonance imaging studies. Undecalcified bone specimens from the patients with Kienbock's disease showed marked osteonecrosis in three patients, focal areas of osteonecrosis in two patients, and alternating areas of osteonecrosis with dramatic areas of new bone formation in one patient. Although in four patients the diagnosis was obvious by plain radiographs, magnetic resonance imaging studies were essential in confirming the diagnosis in two patients and were helpful in ruling out the diagnosis in three patients. PMID- 2269778 TI - Internal fixation of a capitate fracture with Herbert screws. AB - A case of an isolated, displaced fracture of the capitate is described. This rare carpal injury was treated by internal fixation with two Herbert screws. The fracture united and the patient achieved an excellent range of wrist motion. The Herbert screw is useful in the treatment of displaced fractures of the capitate since the screw maintains reduction, compresses the fracture site, and allows early wrist motion. PMID- 2269779 TI - Bilateral unicameral bone cysts in the hamate bones. AB - This is a case report of bilateral unicameral bone cysts located in the hamate bones of a 22-year-old man. Unicameral bone cysts are rarely seen in the bones of the hand or bilaterally. In this case the diagnosis was made clinically using both radiographic and magnetic resonance imaging studies, and verified by microscopy of the biopsied specimen. Treatment consisted of curettage, autogenous bone grafting, and immobilization. To our knowledge there has not been any record in the literature of symmetrical unicameral bone cysts in the carpal bones. PMID- 2269780 TI - Surgical management of ulnar artery aneurysms. AB - In a ten-year review (1978 to 1988), ten ulnar artery aneurysms in nine male patients were studied. Blunt trauma led to 70%, penetrating trauma to 20%, and 10% had no history of trauma. Three cases were seen as asymptomatic palmar masses with brief antecedent histories of 4 weeks or less. Seven patients with aneurysms had persistent vascular hand symptoms for 6 weeks or longer. All seven symptomatic lesions proved to be sources of emboli. Diagnostic arteriography was done in all cases. Intraoperative digital plethysmography aided in operative decisions regarding the necessity for microvascular reconstruction. Five aneurysms were resected with end-to-end ulnar artery microvascular repairs, four resected without repair, and a single case treated with long-term anticoagulants. Follow-up, averaging 40 months, showed uniform improvement in vascular symptoms, with no loss of jeopardized tissues. Ulnar artery aneurysms, well studied preoperatively and intraoperatively, can be treated successfully with selective microvascular reconstruction. PMID- 2269781 TI - Preliminary assessment of laser Doppler flowmetry for determining timing of division of the cross-finger flap. AB - The elapsed time before division of the cross-finger flap depends on adequate neovascularization from the recipient digit. Although subjective assessment of capillary filling in the flap after application of a tourniquet to the donor finger usually is accurate, on occasion, interpretation of observations may be equivocal. In these circumstances, noninvasive office measurement with use of the laser Doppler permits a sequential determination of relative flap perfusion. This objective data facilitates an appropriate clinical decision by the hand surgeon to ensure flap viability after pedicle division. PMID- 2269782 TI - Traumatic infected pseudoaneurysm of the hand. AB - A rare case of ruptured infected pseudoaneurysm of the hand resulting from penetrating trauma is reported. The patient was seen initially with an acute infection of the hand associated with pulsatile bleeding. Diagnostic evaluation should include arteriography as a guide for the operative plan. PMID- 2269783 TI - Wrist injuries: correlation of clinical and arthroscopic findings. AB - Wrist arthroscopy was done for one hundred nine patients with chronic wrist pain, averaging 22.8 months in duration. History regarding mechanism of injury, painful crepitus, pain with activity or at rest, localization of tenderness, visible swelling, and instability with examination was compared with arthroscopic findings of ligament damage, articular cartilage damage, and synovitis. Both pain at rest and swelling correlated significantly with synovitis. Tenderness did not correlate with specific ligament injury. Wrist ligament injuries and/or cartilage damage were noted in 96.3% of these wrists. Ligament injuries were frequently multiple, averaging 2.6 ligament injuries per wrist. No significant association was found between the presence of chondromalacia, synovitis, or specific ligament tears and the mechanism of injury, duration of symptoms, presence of clicking, or pain with activity. PMID- 2269784 TI - Reconstruction of the triangular fibrocartilage complex after surgery for treatment of synovial osteochondromatosis of the distal radioulnar joint. AB - Synovial osteochondromatosis of the hand is uncommon, except for tenosynovial chondromatosis of the digits. It is even more rare in the wrist joint. A patient with synovial osteochondromatosis of the distal radioulnar joint that involved the triangular fibrocartilage complex is described. At operation, synovectomy, excision of osteochondral bodies, and removal of the entire triangular fibrocartilage complex was done. The triangular fibrocartilage complex was reconstructed using part of the extensor carpi ulnaris tendon. One year after operation, the patient had regained almost full range of motion and is without pain. PMID- 2269785 TI - An effective method of reconstructing posttraumatic dorsal dislocated distal radioulnar joints. AB - A new method of reconstructing a posttraumatic dorsally dislocated distal radioulnar joint with use of a long, distally attached palmaris longus tendon strip is described. This sling holds the dislocated distal ulna radially and volarward. Long-term results have been excellent. PMID- 2269786 TI - Allograft replacement with distal radioulnar joint fusion and ulnar osteotomy for treatment of giant cell tumors of the distal radius. AB - Three patients with advanced giant cell tumors of the distal radius received a frozen allograft replacement of the distal radius, accompanied by a distal radioulnar arthrodesis with ulnar osteotomy proximal to the wrist. Follow-up ranged from 2 to 4 years. During this time this combined procedure provided the following advantages: complete tumor resection, no donor site morbidity, retention of pronation-supination, and avoidance of pain or subluxation at the distal radial ulnar joint. PMID- 2269787 TI - Carpal tunnel changes and median nerve compression during wrist flexion and extension seen by magnetic resonance imaging. AB - Magnetic resonance imaging was done on the wrists of 14 volunteer subjects with the wrists in the neutral position, then flexed and extended at 45 degrees. Computer enhanced cross-sectional areas were measured on each subject at the level of the hook of the hamate. In the neutral position the distance between confining structures around the median nerve is 2.0 +/- 0.2 mm in the anteroposterior direction, and the mean cross-sectional area of the carpal tunnel is 1.52 cm2. With the wrist in the extended position the distance available for the median nerve measures 2.2 +/- 0.4 mm and the cross-sectional area increases to 1.75 cm2. When the wrist is flexed, the distance available for the median nerve between the flexor tendons and transverse carpal ligament decreases to 1.1 +/- 0.4 mm, and the cross-sectional tunnel area decreases to 1.36 cm2. Flexion of the wrist and/or fingers both produces a palmar rearrangement of the flexor tendons creating potential compression of the median nerve. The nerve responds to these forces by becoming interposed in various positions between the superficial flexor tendons. PMID- 2269788 TI - Carpal tunnel syndrome secondary to wrist and finger flexor spasticity. AB - Ten patients with spastic wrist flexion deformities secondary to traumatic brain injury were evaluated for carpal tunnel syndrome. The angle of wrist flexion deformity averaged 75 degrees (range, 58 to 115 degrees). Nerve conduction studies demonstrated prolonged median motor and/or sensory latencies in all patients. Preoperative wick catheter measurements of carpal tunnel pressures in eight patients averaged 11 mm Hg in the resting position, 21 mm Hg in maximal wrist flexion, and 15 mm Hg in maximal extension. Each patient had carpal tunnel release with simultaneous wrist and finger flexor tendon releases or lengthenings. At surgery nine of the median nerves were constricted at the proximal edge of the transverse carpal ligament. The presence of normal carpal tunnel pressures and impingement of the median nerve at the proximal edge of the transverse carpal ligament indicates that the chronically flexed posture of the wrist resulted in median nerve compression, and this condition may be aggravated by underlying pressure from the spastic finger flexors. PMID- 2269789 TI - Double loop locking suture: a technique of tendon repair for early active mobilization. Part I: Evolution of technique and experimental study. AB - This article describes a technique of tendon repair and two variations using double loop locking sutures. Experimental study on human tendon specimens showed that the average tensile strength of tendon junctures was 4400 grams by double loop locking sutures and 2252 grams by Kessler's technique. The study also showed that the weakest point of the tendon juncture by double loop locking sutures was the sutures. PMID- 2269790 TI - Double loop locking suture: a technique of tendon repair for early active mobilization. Part II: Clinical experience. AB - Tendons repaired by double loop locking sutures show sufficient strength to allow early active mobilization under protective splint. Clinical experience with 51 tendons repaired by this technique resulted in satisfactory functional recovery. Eleven flexors in zone II showed excellent results in 10 and good results in 1 by the Strickland formula. Early active mobilization of repaired tendons with double loop locking sutures seems to enhance their healing by the intrinsic mechanism and reduce extrinsic adhesion formation and stiff joints. PMID- 2269791 TI - A complication of the buried suture. AB - A buried suture used in the repair of the central slip of a digital extensor resulted in an erosive lesion of the proximal interphalangeal joint of the long finger. In a review of the literature I can find no other reports describing this unusual complication. PMID- 2269792 TI - Long-term results of extensor tendon repair. AB - A retrospective analysis was done in 62 patients with 101 digits having extensor tendon injury. Quality of outcome and parameters that might influence outcome were evaluated. The majority of patients were treated with conventional static splinting. Sixty percent of all fingers sustained an associated injury (fracture, dislocation, joint capsule or flexor tendon damage). Patients without associated injuries achieved 64% good/excellent results, and total active motion of 212 degrees. This difference was statistically significant (p less than 0.05). Distal zones (1 to 4) had a significantly poorer result than more proximal zones (5 to 8). The percentage of fingers losing flexion was greater than the percentage of fingers losing extension. In addition, the average degree loss of flexion was greater than the average degree loss of extension. This would seem to indicate that loss of flexion may be a more significant complication from extensor tendon injury than previously thought. PMID- 2269793 TI - Traumatic and spontaneous dislocation of extensor tendon of the long finger. AB - Extensor tendon dislocation is an unusual problem in patients unaffected by rheumatoid arthritis. Sixteen cases of ulnar dislocation of the long extensor tendon of the long finger are reported. Five of these cases were classified as traumatic dislocation and 11 as spontaneous dislocation. All cases were treated by surgery. Differences in anatomic and clinical features between traumatic and spontaneous dislocation of the long extensor tendon are described. PMID- 2269794 TI - Distal stenosing tenosynovitis. AB - Three patients are described with distal stenosing tenosynovitis involving the flexor digitorum profundus and the A3 pulley. One patient had isolated distal stenosing tenosynovitis and two patients had combined distal and proximal stenosing tenosynovitis of the flexor digitorum superficialis and the A1 pulley. All three patients with four digits involved had improvement of their symptoms after release of the A3 pulley. When involved, the A1 pulley was released at the same time. Patients with proximal stenosing tenosynovitis may have an associated distal stenosing tenosynovitis that if overlooked may cause persistence of symptoms after surgical treatment. PMID- 2269795 TI - Proximal phalangeal fracture after tendon pulley reconstruction. AB - A case is presented in which an A2 pulley reconstruction was done, encircling a previously fractured, multiply-operated proximal phalanx. Bone resorption occurred directly under the pulley, and the bone then fractured. It is postulated that the cumulative effect of these operations on the blood supply to the bone and abnormal pressure forces led to resorption of bone and subsequent fracture. PMID- 2269796 TI - Keratoacanthoma necessitating metacarpal amputation. AB - Keratoacanthoma is usually considered a benign self-limiting lesion. First described in 1888 by Hutchinson, it most commonly involves the face and hands. It is usually controlled by complete soft tissue excision. A variant, subungual keratoacanthoma, affects bone by pressure erosion of the distal phalangeal tip. We report a case of keratoacanthoma clinically involving a metacarpal and phalanges with a radiologic and physical appearance at variance with previous reports. After multiple recurrences following erosion and cryosurgery, as well as attempted digit salvage with Mohs' surgery, ray amputation was required. The world literature pertaining to keratoacanthoma is reviewed and discussed. PMID- 2269797 TI - Simultaneous laceration of the median and ulnar nerves with flexor tendons at the wrist. AB - Simultaneous laceration of both major nerves with flexor tendons at the wrist is a combination injury familiar to any hand surgeon, which has received scant attention in the English-language literature. The causes and pattern of injury in twenty-six patients treated for this condition over a 10-year period were reviewed. Intensive reassessment of eight of these patients revealed good restoration of hand mobility and strength from the repair of tendons, but the results of nerve repair were less reliable. Tests of hand function indicated that the majority had compensated well for their impairments and seven of the eight had returned to full employment. PMID- 2269798 TI - Epineural ganglion of the ulnar nerve at the elbow. AB - Ganglion cysts of peripheral nerves in the upper extremity are rare. Cysts located in the substance of the nerve and extraneural ganglia that cause symptomatic nerve compression have been reported. Intraneural ganglia may be difficult to separate from the neural elements without resultant nerve injury. This case involved a ganglion cyst confined to the epineurium of the ulnar nerve at the elbow. Because of the peripheral location, it was removed without damage to the underlying nerve. PMID- 2269799 TI - Boutonniere rheumatoid thumb deformity. AB - The boutonniere deformity is the most common rheumatoid thumb deformity. It can be classified into early, moderate, and advanced types, depending on whether the deformity is passively correctable. Fifty-three patients with 74 procedures form the basis of these recommendations. The early type treated with metacarpophalangeal joint synovectomy and extensor pollicis longus rerouting have a high recurrence rate of 64%. Metacarpophalangeal joint fusion is the procedure of choice for the moderate type with isolated metacarpophalangeal joint involvement. Metacarpophalangeal joint arthroplasty is best suited for the low demand, older patients with borderline proximal and distal joints. Interphalangeal joint releases done with metacarpophalangeal joint fusions have a high recurrence rate and are not recommended. In advanced cases metacarpophalangeal joint arthroplasty and interphalangeal joint fusion is our procedure of choice. PMID- 2269800 TI - Effects of morphine on the dyspnea of terminal cancer patients. AB - We report an open, uncontrolled study designed to assess the effects of subcutaneous (SC) morphine on dyspnea of terminal cancer. Twenty patients with dyspnea caused by restrictive respiratory failure received an SC dose of morphine of 5 mg (5 patients who were not receiving narcotics), or equivalent to 2.5 times their regular dose (15 patients who were receiving narcotics for pain). Dyspnea (D) and pain (15 cases) were measured before the dose and every 15 min for 150 min after the injection using a visual analog scale 0-100. Respiratory rate (RR), respiratory effort (RE) (score 1-6), arterial saturation of O2 (SO2) and end tidal PACO2 were determined before and 45 min after SC morphine. D, RR, RE, SO2, and PACO2 were 68 +/- 32, 32 +/- 7; 3.5 +/- 1.8, 87 +/- 10, and 31 +/- 12, respectively, before SC morphine, and 34 +/- 25 (P less than 0.001), 31 +/- 9 (P:NS), 3.2 +/- 1.9 (P:NS), 86 +/- 11 (P:NS), and 33 +/- 9 (P:NS), respectively, 45 min after SC morphine. Nineteen of 20 patients (95%) reported improved dyspnea after morphine. We conclude that morphine appears to improve dyspnea without causing a significant deterioration in respiratory function in terminal cancer patients. Double-blind placebo controlled studies are needed in this population. PMID- 2269801 TI - Attitudes about cancer pain: a survey of Wisconsin's first-year medical students. AB - A brief questionnaire was administered to 317 first-year students at Wisconsin's two medical schools to assess their attitudes about cancer pain prior to their entry into medical school. Although the students had a realistic perspective of the prevalence and severity of cancer pain, they displayed a number of negative attitudes that if unchanged would contribute to future inadequate pain treatment. Students (a) greatly exaggerated the incidence of psychological dependence (addiction) in patients treated with opioid analgesics, (b) inappropriately timed maximal analgesic therapy to the duration of life expectancy, (c) felt that a majority of patients with cancer currently receive adequate or excessive analgesic therapy, and (d) believed that increasing pain was invariably related to the development of drug tolerance rather than to progression of the disease. Curricular efforts need to be directed at bringing about changes in students' negative attitudes about cancer pain and its management. PMID- 2269802 TI - Discordance between self-report and behavioral pain measures in children aged 3-7 years after surgery. AB - This study examined concurrent self-reports of pain intensity and behavioral responses in 25 children aged 3-7 yr. Behavioral (Children's Hospital of Eastern Ontario Pain Scale, CHEOPS) and self-report (the Oucher and Analogue Chromatic Continuous Scale) measures of pain were obtained following major surgery. The two self-report measures were strongly and significantly correlated, and the pattern of scores over the 36-hr observation period was as expected. There was little relationship between the scores for the self-report and the behavioral measures. Many children who reported severe pain manifested few of the behavioral indicators of distress used in the CHEOPS. This behavioral response pattern may occur commonly in children experiencing pain after surgery and may limit the applicability of current behavioral scales as sole measures of pain intensity in younger children. PMID- 2269803 TI - Intravenous regional sympatholysis: a double-blind comparison of guanethidine, reserpine, and normal saline. AB - This double-blind, randomized study was designed to compare the effectiveness of intravenous regional sympatholysis using guanethidine, reserpine and normal saline. Twenty-one patients with reflex sympathetic dystrophy of an upper or lower extremity were enrolled and received intravenous regional blockade (IVRB) with one of the three medications. There was significant pain relief in all three groups at 30 min. There were no significant differences among the three groups in the degree of pain relief, the number of patients obtaining pain relief in the 30 min after the block, or the number of patients reporting more than 50% pain relief for more than 24 hr. The saline group's high rate of pain relief could be partially due to a mechanism of tourniquet-induced analgesia. PMID- 2269804 TI - Patient-controlled antiemesis for cancer chemotherapy-induced nausea and vomiting. AB - Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient-controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (greater than 3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of difficult-to-treat patients. PMID- 2269805 TI - [Recent problems on lupus systemic erythematosus]. PMID- 2269806 TI - [Etiologic mechanism of systemic lupus erythematosus]. PMID- 2269807 TI - [Clinical symptoms and diagnostic criteria of systemic lupus erythematosus]. PMID- 2269808 TI - [Diagnostic tests and monitoring of systemic lupus erythematosus]. PMID- 2269809 TI - [Diagnosis and clinical symptoms of systemic lupus erythematosus and overlap syndrome]. PMID- 2269810 TI - [Classification and therapy of systemic lupus erythematosus]. PMID- 2269811 TI - [Important points in adrenal-corticosteroid therapy of systemic lupus erythematosus]. PMID- 2269812 TI - [Apheresis therapy of systemic lupus erythematosus]. PMID- 2269814 TI - [Clinical symptoms and therapy of central-nervous lupus erythematosus]. PMID- 2269813 TI - [Clinical symptoms and therapy of lupus nephritis]. PMID- 2269815 TI - [Clinical study and therapy of pulmonary hypertension in systemic lupus erythematosus]. PMID- 2269816 TI - [Clinical study and therapy of primary anti-phospholipid syndrome]. PMID- 2269817 TI - [Clinical concept of lupus cystitis]. PMID- 2269818 TI - [Clinical study and therapy of systemic lupus erythematosus and pregnancy]. PMID- 2269819 TI - [Countermeasure for adverse effects of therapeutic agents for systemic lupus erythematosus]. PMID- 2269820 TI - [Diagnostic approach to systemic lupus erythematosus from the point of view of the symptoms]. PMID- 2269821 TI - [Autopsy case of immunoproliferative small intestinal disease]. PMID- 2269822 TI - [A case of multiple cerebral palsy manifesting facial paralysis and positive Borrelia burgdorferi antibody]. PMID- 2269823 TI - [A case of high blood level of immunoglobulin-binding SGOT]. PMID- 2269824 TI - [A case of McCune-Albright syndrome]. PMID- 2269825 TI - The boutonniere injury. PMID- 2269826 TI - Factors influencing the results of implant surgery in the rheumatoid hand. PMID- 2269827 TI - Early mobilisation of acute middle slip injuries. AB - After operative repair, the conventional management of open injuries to the middle slip of the extensor tendon involves prolonged immobilisation of the P.I.P. joint. We report our results using controlled mobilisation with a Capener splint after two weeks rigid splintage. In a series of 99 patients seen soon after injury, 88% had excellent or good results after six months. Poor results were more common in patients with complex joint injuries and in patients who did not comply with the treatment. We advocate early mobilisation following repair of the middle slip. PMID- 2269828 TI - Reconstruction of the central slip by the transverse retinacular ligament for boutonniere deformity. AB - A method of repair of boutonniere deformity is described, using the transverse retinacular ligament. Six fingers in five patients were treated by this procedure. The deformity was improved in all fingers; complete or almost complete correction was obtained in four fingers and incomplete correction in two. However, severe limitation of flexion of the D.I.P. joint appeared in two fingers after surgery. This procedure is not indicated for boutonniere deformities with severe contracture of the lateral band; its best indication is in cases in which the central slip is defective and conservative treatment is not effective. PMID- 2269829 TI - Operative treatment of the post-traumatic boutonniere deformity. A modification of the direct anatomical repair technique. AB - We report 20 cases of post-traumatic boutonniere deformity treated by a modification of the direct anatomical repair technique, particularly indicated in late cases which have complete passive motion. A swallow-tailed flap is excised from the fibrous tissue between the two ends of the central slip. The proximal one is then advanced up to the coaptation with the distal edge of the scarred capsular tissue at the insertion on the middle phalanx to which it is sutured in correct tension. Excellent results have been obtained in 72% of cases and good in 5.5%. The 16% of fair results are probably due to the fact that patients didn't use the splint post-operatively and didn't cooperative with physiotherapy. PMID- 2269830 TI - On the priorities of publication of some operative procedures on the distal end of the ulna. AB - A search of the relevant literature concerning various procedures done to the distal ulna in post-traumatic conditions has shown that several terms are inappropriate to the procedures they describe. This paper tries to clarify the situation and help in correct citation. PMID- 2269831 TI - The staged island flap: a new method of repair for thumb injuries. AB - An island flap from the middle finger is described which can be used to cover a terminal wound on the thumb and the adjacent palmar and dorsal defects of the thumb. The flap is transferred in two stages: the first stage ensures good skin cover using a simple technique and the second stage is nerve repair, giving good sensory return with correct cortical representation. Since 1977, 64 repairs have been carried out using this island flap. The follow-up, results and complications are discussed. PMID- 2269832 TI - Mechanical properties of human pulleys. AB - In order to determine the mechanical properties of the fibro-osseous pulleys in the hand, the diaphyseal annular pulleys, the volar plate annular pulleys and the cruciate or condensable portions were tested. A custom-made loading device provided proper fit of the soft tissues for a uniform distribution of the pulley load during testing. The A2 pulley was found to be the strongest of the pulleys; the A1 and A4 were the next strongest. The A3 pulley was nearly equal in mean breaking strength to the other annular pulleys, but in absolute breaking load was considerably weaker because of its shortness. The A4 was the least compliant of the pulleys. We concluded that the fibro-osseous A2 and A4 were mechanically stronger and stiffer pulleys than the A1, A3, A5 (volar plate) pulleys. In testing one type of pulley reconstruction, we found that the "belt loop" technique of Karev nearly matched the annular pulleys in strength and energy absorption. PMID- 2269833 TI - The mechanical effect of partial resection of the digital fibrous flexor sheath. AB - In the context of primary flexor tendon repair, a study has been made to determine how much of the flexor sheath may be opened without causing mechanical disadvantage to the finger. In five cadaver hands, measurement of profundus tendon excursion, distance from nail to distal palmar crease, profundus flexion force, and tendon bow-stringing, showed that there was no material change of these parameters when up to four contiguous pulleys were divided. Along with other individual pulleys, A2 and A4 cannot be regarded as inviolate. PMID- 2269834 TI - Elastic band mobilisation after flexor tendon repair; splint design and risk of flexion contracture. AB - Elastic band mobilisation of repaired flexor tendons in zone 2 may be complicated by flexion contracture of the P.I.P. joint. The mechanics of three types of elastic band mobilisation were analysed from lateral video-recordings of finger movement and the flexion moment at the P.I.P. joint was derived at every 10 degrees of flexion. The conventional forearm attachment of the elastic band produced a steep rise in P.I.P. joint flexion moment during extension; this effect was greatest when the M.P. joint was at 70 degrees and least at 20 degrees. Flexion moments for attachments around the dorsum of the hand or under a palmar pulley were lower, uniform throughout the range of P.I.P. joint motion and independent of the position of the M.P. joint. The effort needed to extend the P.I.P. joint is strongly influenced by the method of elastic band attachment; consideration should be given to both tension and moment arm in application of elastic band mobilisation. PMID- 2269835 TI - Treatment of trans-scaphoid perilunate dislocations by internal fixation with the Herbert screw. AB - Thirteen patients with 14 dorsal trans-scaphoid perilunate dislocations were treated by open reduction and internal fixation of the scaphoid using a Herbert screw. The follow-up evaluations took place after a mean of 18 months. These perilunate dislocations were only trans-scaphoid in ten wrists, trans-radial styloid and trans-scaphoid in three and trans-scaphoid and trans-capitate in one. Based on Cooney's clinical scoring system, the scores of our series were two excellent, six good, five fair and one poor. This suggests that the Herbert screw can offer satisfactory results in the management of trans-scaphoid perilunate dislocations, despite its technical difficulties. PMID- 2269836 TI - The Herbert screw for delayed and non-union of scaphoid fractures: a review of fifty cases. AB - The results of treatment using the Herbert screw in 50 consecutive patients with delayed or established non-union of the scaphoid are reported. 14% of these fractures failed to unite after operation and a further 20% required prolonged protection, uniting within six months. There were significant technical problems in 28% of operations. A bone graft was only used when there was significant collapse of the scaphoid (52%) and the cases without graft did just as well. Overall, the results do not support the view that this method of treatment is a significant advance over Russe grafting in terms of union rates, but confirm that it produces similar results without the need for prolonged immobilisation and without the need for bone grafting in almost half the cases, although there can be significant technical problems with the procedure. PMID- 2269837 TI - Bilateral spontaneous scapho-lunate subluxation treated by limited carpal fusion. AB - The case of a 19 year-old-girl who developed spontaneous bilateral snapping scapho-lunate subluxation is described. Her symptoms were successfully treated by bilateral triscaphoid fusion. PMID- 2269838 TI - Subcutaneous release of trigger thumb and fingers in 210 fingers. AB - Subcutaneous release of the tendon sheath has been performed in 210 trigger digits of 172 patients. The follow-up period ranged from 3 to 58 months, with an average of 24 months. Based on our points system, the overall results were as follows: excellent 64.3%, good 9.5% fair 8.1%, poor 18.1%. There were no infections, no injuries of nerves or vessels and no functional insufficiency. This subcutaneous procedure can be easily, quickly and safely performed by careful hand surgeons in the out-patient clinic. PMID- 2269839 TI - Trigger thumbs in children: a follow-up study of 37 children below 15 years of age. AB - 37 patients who had been operated upon for trigger thumb, all below 15 years of age, have been reviewed. 75% of the affected thumbs were on the dominant hand and 25% have bow-stringing of 1-2 mm. without any complaints. All had good results. Unlike other authors, we found that operation done after the third year of age gave full correction of the flexion contracture. PMID- 2269840 TI - Trigger finger secondary to soft tissue chondroma. AB - Although chondromata are the most common bony tumours in the hand, soft tissue chondromata are much less frequent. We report a case of trigger finger secondary to a soft tissue chondroma. PMID- 2269841 TI - Experimental study of radial ray deficiency. AB - The teratogenic mechanisms of radial ray deficiency were investigated. Radial ray deficiencies were induced in WKAH/Hkm rat foetuses by maternal administration of myleran on day 10, 10.5, or 11 of pregnancy. The skeletal anomalies in rats were similar to those in human beings, suggesting that exposure to some environmental factors at a sensitive period of embryogenesis may cause radial ray deficiency in humans. Ulnar ray deficiency has also been induced in rat foetuses by maternal administration of myleran, so it is suggested that radial deficiency and ulnar deficiency are caused by a common teratogenic mechanism in humans. However, the critical period for radial deficiency is one day later than that for ulnar deficiency in rats, which may contribute to the greater frequency of radial deficiency than ulnar deficiency in clinical cases. PMID- 2269842 TI - Congenital dislocation of the radial head. AB - A retrospective review of 34 patients with congenital dislocation of the radial head was carried out. In 22 patients, the radial head dislocation was the only abnormality. The range of motion of the elbow and forearm was considerably limited in some patients and did cause functional impairment, especially lack of supination. Increased ulnar length in relation to the radius and a hypoplastic capitellum suggest that a dislocation is congenital. Surgical intervention is seldom necessary. PMID- 2269843 TI - Aneurysmal bone cyst of the proximal phalanx. AB - A case of aneurysmal bone cyst of the proximal phalanx in a young boy with unfused epiphysial plates is reported. Curettage failed, so diaphysectomy and cortical bone grafting were performed, sparing the epiphysial plate. This resulted in normal length and function, and the graft remodelled completely to a normal appearance of tubular bone. PMID- 2269844 TI - Benign haemangioma of bone in a middle phalanx. AB - Haemangioma of bone is a rare benign tumour of blood vessels. We report a case arising in a middle phalanx and the problems encountered in its management. PMID- 2269845 TI - Haemangioma of the digital nerve: a case report. AB - An intra-neural haemangioma of the digital nerve of the left index finger is described, the first report of such a lesion in a digit. Treatment consisted of excision of the tumour and the affected portion of the nerve, followed by direct coaptation of the nerve ends. PMID- 2269846 TI - A case of neurofibroma of the palmar cutaneous branch of the median nerve. AB - This case report describes a previously unreported entity, a neurofibroma of the palmar cutaneous branch of the median nerve. The lesion presented as a palmar mass with an overlying abnormality of the skin. Treatment consisted of excision of the lesion. Infiltration of the terminal branches of the nerve by the tumour prevented nerve reconstruction but provided a previously unknown diagnostic clue: fibrosis of an area of skin innervated by the involved nerve, which had the appearance of a callosity. PMID- 2269847 TI - Posterior interosseous nerve axonotmesis from compression by a ganglion. AB - A complete posterior interosseous nerve palsy resulted from axonotmesis caused by pressure from a ganglion cyst. Excision of the neuroma and interpositional nerve grafting gave a most satisfactory outcome. PMID- 2269848 TI - Radial nerve laceration two years after a stab wound to the distal humerus: a case report. AB - A patient is described who was stabbed in the upper arm and two years later developed a radial nerve palsy. X-rays showed that the tip of the knife had broken off in the arm. At operation this bit of blade was loose and had completely divided the radial nerve. PMID- 2269849 TI - Ulnar translocation after excision of giant cell tumour of distal radius. AB - Translocation of the ipsilateral ulna has been carried out in six cases after radical resection of a giant cell tumour of the distal radius. The carpo-ulnar junction united readily in all cases. Union of the radio-ulnar junction is often delayed, but this can be overcome by the addition of cancellous grafts at the time of ulnar translocation. All the patients had very good forearm rotation and an acceptable appearance. There were no significant complications. PMID- 2269850 TI - Proliferative fasciitis of a finger: a case report. AB - This is the first report of proliferative fasciitis presenting in a finger. This is a benign pseudosarcomatous lesion which normally runs a self-limiting course. PMID- 2269852 TI - Early mobilisation after flexor tendon repair. PMID- 2269851 TI - Scapho-lunate diastasis: a component of fractures of the distal radius. AB - Ten cases of fractures of the distal radius associated with scapho-lunate diastasis are reported. The mechanism of injury has been described and an attempt made to analyse the implications in treating such an injury. PMID- 2269853 TI - The carpal tunnel syndrome: can we do better? PMID- 2269854 TI - Of ethics--of right and wrong. PMID- 2269855 TI - Note concerning the editorial. PMID- 2269856 TI - The medical ethics program at Emory. PMID- 2269857 TI - An address on ethics. PMID- 2269858 TI - Cognitive brain death: the major ethical issue of our time. PMID- 2269860 TI - Health care reform: how deep, how wide? PMID- 2269859 TI - A window on Emory's history: pre- and post-Stead. PMID- 2269861 TI - Health insurance costs: the snake that needs killing. PMID- 2269862 TI - The ethical dilemma: to do or not to do. PMID- 2269863 TI - Ethics in health care: what do we have to do? What should we do? PMID- 2269864 TI - Medical ethics: prolonging life or protracting death? PMID- 2269865 TI - Is it ethical to provide futile care? PMID- 2269866 TI - An ethical dilemma: public safety or personal privacy in reporting HIV infection. PMID- 2269867 TI - The ethical practice of medicine. PMID- 2269868 TI - Angioplasty in complex multivessel disease: will it replace surgery? PMID- 2269869 TI - Switching at the cellular level in the white-opaque transition of Candida albicans. AB - The 'white-opaque transition' in Candida albicans strain WO-1 provides a unique system for analysing high-frequency switching at the cellular level because of the difference in the budding phenotypes of the white and opaque phases. Single white and opaque cells were placed on agar and monitored for the dynamics of cell division, microcolony genesis and switching to the alternative phase. It is demonstrated that at 24 degrees C, opaque cells can switch directly to white cells but white cells first generate an elongate, pseudohyphal-shaped precursor in the transition to an opaque cell. Cells in either phase can generate a daughter cell in the alternative phase, then revert immediately to the genesis of subsequent daughter cells in the original phase. By developing a mathematical model for switching at the cellular level which subtracts mother cells and switched daughter cells from the pool of switching candidates, the probability for an opaque cell to generate a white daughter cell in any single generation was calculated to be 1.0 x 10(-1) and the probability for a white cell to generate an opaque daughter cell in any single generation was calculated to be 1.7 x 10(-5) at 24 degrees C on nutrient agar. The mean number of generations before an opaque cell generated a white daughter cell was calculated to be 3.4 and the mean number before a white cell formed an opaque cell was calculated to be 15.8 at 24 degrees C on nutrient agar. Finally, high-temperature induction of the opaque to white transition was analysed at the cellular level and demonstrated to involve frequent bipolar formation of white daughter cells on the original opaque mother cell, and in some cases intermediate phenotypes. PMID- 2269870 TI - Inhibition of the dimorphic transition of Candida albicans by the ornithine decarboxylase inhibitor 1,4-diaminobutanone: alterations in the glycoprotein composition of the cell wall. AB - Hyphal development in Candida albicans was selectively blocked by the ornithine decarboxylase competitive inhibitor 1,4-diaminobutanone (DAB). Inhibition of hyphal development required DAB during both yeast inoculum growth and subsequent incubation at 37 degrees C to induce mycelial growth. This effect was not due to general growth inhibition since DAB did not inhibit yeast growth, and reduced protein synthesis by 30% at most. Moreover, protein synthesis was unaffected by DAB when cells were pre-grown in drug-containing media. Since DAB inhibited dimorphic transition at 37 degrees C, morphology- and temperature-dependent protein synthesis could be distinguished. DAB stimulated the synthesis of several yeast wall-proteins, irrespective of morphology or growth temperature, and two at 37 degrees C only, but it inhibited the synthesis of a single mycelial-specific glycoprotein species. PMID- 2269871 TI - Purification and properties of an extracellular endoglucanase from Myceliophthora thermophila D-14 (ATCC 48104). AB - An extracellular endoglucanase (1,4-beta-glucanohydrolase, EC 3.2.1.4) produced by Myceliophthora thermophila D-14 (ATCC 48104) has been purified to homogeneity by ammonium sulphate precipitation and two consecutive ion-exchange chromatographic steps on DEAE-Sephadex A-50 columns. The enzyme was purified 13.8 fold and was homogeneous by analytical PAGE and SDS-PAGE. It has a high apparent Mr, of about 100,000. The pH and temperature optima for its activity were 4.8 and 65 degrees C respectively. The Km of the purified enzyme for CMC (sodium salt) was 3 mg ml-1. The enzyme displayed low activity toward salicin and p-nitrophenyl beta-D-glucoside. The activity was enhanced in the presence of Na+, K+ and Ca2+ but effectively inhibited by Hg2+, Fe2+, Mg2+, Cu2+ and NH4+. Inhibition studies indicated that the enzyme may be a metalloprotein and/or that it requires metal ions for its optimum activity. PMID- 2269872 TI - Investigation of the structure and localization of the urease of Helicobacter pylori using monoclonal antibodies. AB - The urease of Helicobacter pylori (formerly Campylobacter pylori) has been partly purified by fast protein liquid chromatography. This material contained 10 nm doughnut-like structures when examined by electron microscopy and comprised three major polypeptides (61 kDa, 56 kDa and 28 kDa). Only two of these polypeptides (61 kDa and 28 kDa) were observed in urease-containing material isolated by preparative non-denatured PAGE. Monoclonal antibodies (mAbs) were produced which were directed against two of these polypeptides (56 kDa and 28 kDa). Only mAbs directed against the 28 kDa polypeptide inhibited or captured urease activity. These results suggest that the 56 kDa polypeptide is not essential for enzyme activity. Anti-urease mAbs were used in an indirect immunogold technique to localize the enzyme at the ultrastructural level. In both prefixed bacteria and ultrathin cryosectioned bacteria the enzyme was located on the cell surface and in material apparently shed from that surface. PMID- 2269873 TI - Subcellular localization of Mycobacterium leprae-specific phenolic glycolipid (PGL-I) antigen in human leprosy lesions and in M. leprae isolated from armadillo liver. AB - Phenolic glycolipid (PGL-I), an antigen specific to Mycobacterium leprae, was localized subcellularly in M. leprae residing in human skin, in M. leprae isolated from armadillo liver ('isolated M. leprae') and outside M. leprae in human lepromatous skin. For a quantitative localization of PGL-I sites, specimens, including skin segments stored for 6 years in glutaraldehyde, were embedded in hydrophilic Lowicryl (K4M) resin for ultrathin sectioning. Ultracryosections and Araldite sections of comparable specimens were used for comparison of localization results. A monoclonal antibody (F 47-21-3) directed to antigenic oligosaccharide of PGL-I was employed as primary antibody in immunogold labelling of ultrathin sections. K4M-immunogold methods gave very satisfactory quantitative gold-labelling of PGL-I. The localization of PGL-I by this method partially corresponded with sites detectable in both ultracryosections and the qualititatively superior Araldite sections, but new sites were also localized. Cell walls in human M. leprae and in isolated M. leprae possessed many PGL-I sites, particularly in dividing organisms. PGL-I or its antigenic oligosaccharide was also found, to a lesser extent, in the bacterial cytoplasm. Capsules discernible around part of isolated M. leprae cells displayed heavy PGL-I labelling, sometimes clearly confined to a zone distant from the cell wall. Extrabacterial PGL-I in M. leprae-infected human skin was encountered (1) in phagolysosomes and cytoplasm proper of dermal macrophages containing M. leprae, and (2) intra- and extracellularly in epidermal areas where basal cells harboured M. leprae in untreated multibacillary patients. PMID- 2269874 TI - Cloning and sequencing of a [NiFe] hydrogenase operon from Desulfovibrio vulgaris Miyazaki F. AB - A hydrogenase operon was cloned from chromosomal DNA isolated from Desulfovibrio vulgaris Miyazaki F with the use of probes derived from the genes encoding [NiFe] hydrogenase from Desulfovibrio vulgaris Hildenborough. The nucleic acid sequence of the cloned DNA indicates this hydrogenase to be a two-subunit enzyme: the gene for the small subunit (267 residues; molecular mass = 28763 Da) precedes that for the large subunit (566 residues; molecular mass = 62495 Da), as in other [NiFe] and [NiFeSe] hydrogenase operons. The amino acid sequences of the small and large subunits of the Miyazaki hydrogenase share 80% homology with those of the [NiFe] hydrogenase from Desulfovibrio gigas. Fourteen cysteine residues, ten in the small and four in the large subunit, which are thought to co-ordinate the iron sulphur clusters and the active-site nickel in [NiFe] hydrogenases, are found to be conserved in the Miyazaki hydrogenase. The subunit molecular masses and amino acid composition derived from the gene sequence are very similar to the data reported for the periplasmic, membrane-bound hydrogenase isolated by Yagi and coworkers, suggesting that this hydrogenase belongs to the general class of [NiFe] hydrogenases, despite its low nickel content and apparently anomalous spectral properties. PMID- 2269875 TI - Cloning and sequencing of the celA gene encoding endoglucanase A of Butyrivibrio fibrisolvens strain A46. AB - Genomic DNA from Butyrivibrio fibrisolvens strain A46 was digested with EcoRI and ligated into lambda gt11. Two recombinant phages isolated from the gene bank hydrolysed carboxymethylcellulose and were shown to contain the same 2.3 kb EcoRI restriction fragment, which was cloned into pUC12 to generate pBA46. Escherichia coli JM83 harbouring pBA46 expressed an endoglucanase (EGA) which hydrolysed a range of other substrates including barley beta-glucan, Avicel, filter paper and p-nitrophenyl beta-D-cellobioside. Nucleotide sequencing of the B. fibrisolvens strain A46 DNA cloned in pBA46 revealed a single open reading frame (ORF) of 1296 bp, encoding a protein of 48,863 Da. Confirmation that the ORF coded for EGA was obtained by comparing the N-terminal sequence of the purified endoglucanase with that deduced from the nucleotide sequence. EGA contains a typical prokaryotic signal peptide at its N-terminus and shows some homology with the Bacillus family of cellulases. The enzyme does not contain distinct functional domains, which are prevalent in cellulases from Pseudomonas fluorescens subsp. cellulosa and Cellulomonas fimi. PMID- 2269876 TI - Transfer of plasmid DNA to Brevibacterium lactofermentum by electrotransformation. AB - The Escherichia coli-Brevibacterium lactofermentum shuttle vector pBLA was introduced into intact cells of B. lactofermentum by electrotransformation. Several parameters of this procedure such as voltage and cell concentration were analysed. Optimal conditions gave an efficiency of 10(6) transformants per microgram of DNA. Two recalcitrant strains could be electrotransformed when an ampicillin pretreatment step was used. Electrotransformation experiments using DNAase or different structural forms of plasmid DNA showed that the electrotransformation process is quite different from natural transformation involving competence development. Restriction-modification-proficient B. lactofermentum could be efficiently electrotransformed with pBLA DNA isolated from E. coli. This restriction-modification system therefore seems to be overcome by electrotransformation. Thus electrotransformation may efficiently replace the protoplast bacterial transformation method. PMID- 2269877 TI - Requirement of the Escherichia coli dnaK gene for thermotolerance and protection against H2O2. AB - Thermotolerance in Escherichia coli is induced by exposing cells to a brief heat shock (42 degrees C for 15 min). This results in resistance to the lethal effect of exposure to a higher temperature (50 degrees C). Mutants defective in the recA, uvrA and xthA genes are more sensitive to heat than the wild-type. However, after development of thermotolerance these mutants are like the wild-type in their heat sensitivity. This suggests that thermotolerance is an inducible response capable of protecting cells from the lethal effects of heat, independently of recA, uvrA and xthA. Thermotolerance does not develop in a dnaK mutant. In addition, the dnaK mutant is sensitive to heat and H2O2, but is resistant to UV irradiation. This implies that the E. coli heat-shock response includes a mechanism that protects cells from heat and H2O2, but not from UV. PMID- 2269878 TI - Differentiation between Actinobacillus (Haemophilus) actinomycetemcomitans, Haemophilus aphrophilus and Haemophilus paraphrophilus by multilocus enzyme electrophoresis. AB - Genetic relationships among isolates assigned to Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus and H. paraphrophilus were determined by analysis of electrophoretically demonstrable allelic variation in 14 structural genes encoding metabolic enzymes. Among the 51 isolates analysed there were 25 electrophoretic types (ETs), among which mean genetic diversity per locus was 0.753. Cluster analysis of ETs demonstrated one well-defined group of 11 ETs representing solely the genotypes of all 17 isolates assigned to A. actinomycetemcomitans. The remaining 14 ETs represented the genotypes of the 34 isolates of H. aphrophilus and H. paraphrophilus. With the exception of ATCC 13252, all strains of H. aphrophilus were closely related, whereas strains assigned to H. paraphrophilus included distantly related lineages, some of which were similar to those of H. aphrophilus and should be assigned to this species. Thus, the study showed that there is no significant overall genetic similarity between A. actinomycetemcomitans and the two Haemophilus spp. PMID- 2269879 TI - Isolation and preliminary characterization of antigenic variant of echovirus type 11. AB - Nosocomial infection with echovirus type 11 resulting in aseptic meningitis occurred among newborn babies in a hospital neonatal room at Fukui city. The virus was identified as a variant of echovirus type 11 by cross-neutralization tests with antisera against the prototype Gregory strain and the current Fukui isolate. Fukui isolates expressed strain specific antigen(s) in addition to type specific common antigen(s), but lacked a certain antigen(s) which was present in the prototype strain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of virus polypeptides revealed that the capsid proteins VP2 and VP3 of Fukui strain migrated more rapidly than the Gregory strain, while both strains had the same migration pattern of VP1 protein on which the antigenic determinants responsible for virus neutralization were present. The current strain produced large plaques and was more thermoresistant, suggesting some alterations in the structural proteins of the virus. PMID- 2269880 TI - Hepatitis B virus clearance from serum and liver after acute hepatitis delta virus superinfection in chronic HBsAg carriers. AB - Clinical, virological, and histological findings in four HBsAg chronic carriers who cleared HBV markers from both serum and liver following HDV superinfection are described. The patients were long-term HBsAg carriers and all were HBV DNA/HBeAg positive. Liver biopsy, obtained from three of the patients between 5 and 15 months prior to HDV superinfection, showed chronic persistent hepatitis in two and chronic active hepatitis in one. During the follow-up of 9-19 months, the patients completely recovered from acute delta hepatitis with termination of HBsAg carriage and regression of the histological feature of chronic liver damage. These data demonstrate that sometimes HDV is able to induce a permanent inhibition of its helper virus. HDV superinfection probably enhances the immune clearance of infected cells during the replicative phase of chronic HBV infection. PMID- 2269881 TI - High genomic variability in the pre-C region of hepatitis B virus in anti-HBe, HBV DNA-positive chronic hepatitis. AB - Some chronic HBV carriers have circulating HBV DNA despite the presence of anti HBeAg antibodies. This observation has recently been related to the presence, in the HBV pre-C region, of a translational stop codon that prevents HBeAg synthesis. In the present study, we analyzed, at the nucleotide level, the pre C/C region of HBV isolated from the sera of 11 anti-HBe, HBV DNA-positive chronic carriers. Nucleotide sequence analysis of 25 independent clones revealed that the pre-C sequence is highly variable, even among clones derived from the same serum sample. Moreover, our data show that HBeAg synthesis can also be prevented by as yet undescribed T-C substitution at position 1815 that eliminates the start codon of the pre-C transcript. These results suggest that the HBV genome contains segments of high variability that have probably been selected during evolution to favor the segregation of functionally advantaged mutants capable of avoiding host immunity. PMID- 2269882 TI - Different forms of hepatitis B virus DNA and expression of HBV antigens in peripheral blood mononuclear cells in chronic hepatitis B. AB - The presence of both hepatitis B virus (HBV) DNA and HBV antigens (HBsAg, HBeAg) was assessed in peripheral blood mononuclear cells (PBMC) from 32 patients chronically infected with HBV. Three different molecular forms of HBV DNA were observed: free monomers (5), high-molecular-weight free concatemers (11), and integrated HBV DNA (9). The HBV DNA patterns in the PBMC were different from those found in liver and did not correlate with any specific profile of serum HBV markers. When the same PBMC were assayed for HBsAg, 22 of the 25 HBV DNA positive samples, but only three of the seven HBV DNA negative samples, were positive. By contrast, none of the PBMC samples from five healthy HBV vaccine recipients gave any positive signal in the HBV DNA or HBsAg assays. In some patients, T and B cells, monocytes, and polymorphonuclear (PMN) cells were assayed separately, showing that the DNA pattern was similar for these different leucocytes subsets and ruling out the possibility that these patterns might reflect PMN cell contamination. Thus, in chronic HBV infection, 87.5% (28/32) of patients were found to contain at least one HBV marker in their PBMC, and a strong correlation was found between the presence of HBV DNA and viral antigens, suggesting a specific expression of HBV encoded proteins. PMID- 2269883 TI - Neurogranin: immunocytochemical localization of a brain-specific protein kinase C substrate. AB - The developmental expression and the cellular localization of neurogranin (formerly designated p17), a brain-specific protein kinase C (PKC) substrate, were investigated. The developmental expression of neurogranin was studied by immunoblotting of rat brain and neuronal cell-culture extracts using neurogranin polyclonal antibodies. Neurogranin synthesis was found to be developmentally regulated, with no expression in the embryonic and neonatal period and an abrupt increase between 2 and 3 weeks of age. By immunohistochemistry, neurogranin was found essentially in the adult rat telencephalon, specifically located in the cell bodies and dendritic processes of neurons of the cerebral cortex, hippocampus, striatum, and a few other discreet areas. Neurogranin immunoreactivity was nearly absent in the thalamus, cerebellum, and brain stem. The late developmental expression and the dendritic localization of neurogranin in neurons are 2 features that also characterize the type I PKC isozyme. The specific localization of the protein in integrative areas of the rat brain suggests a highly specialized function of neurogranin in the CNS. A possible role for neurogranin in the transduction of the PKC activation signals at the postsynaptic level is suggested. PMID- 2269884 TI - Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. AB - NGF, a trophic polypeptide, is necessary for the normal development and survival of certain populations of neurons in the CNS and PNS. In the CNS, cholinergic neurons of the basal forebrain magnocellular complex (BFMC) are prominent targets of NGF. During rat development, NGF increases the activity of ChAT in these neurons. In adult rats with experimental injury of axons in the fimbria-fornix, NGF prevents degenerative changes in axotomized cholinergic BFMC neurons in the medial septal nucleus (MSN). Because the amino acid sequences of NGF and its receptor (NGF-R) are highly conserved across species, we hypothesized that mouse NGF would also prevent degeneration of cholinergic BFMC neurons in nonhuman primates. Therefore, the present study was designed to test whether fimbria fornix lesions result in retrograde degenerative changes in basal forebrain cholinergic neurons in macaques, whether these changes are prevented by mouse NGF, and whether the protective effect of NGF is selective for cholinergic neurons of the basal forebrain. Following unilateral complete transection of the fornix, animals were allowed to survive for 2 weeks, during which time half of the subjects received intraventricular NGF in vehicle and the other half received vehicle alone. In animals receiving vehicle alone, there was a 55% reduction in the number of ChAT-immunoreactive cell bodies within the MSN ipsilateral to the lesion; loss of immunoreactive somata was more severe in caudal planes of the MSN. Remaining immunoreactive neurons appeared smaller than those in control, unoperated animals. In Nissl stains, there was no apparent loss of basophilic profiles in the MSN, but cells showed reduced size and intensity of basophilia. Treatment with NGF almost completely prevented reductions in the number and size of cholinergic neurons and had a significant general effect in preventing atrophy in basophilic magnocellular neurons of the MSN, though some basophilic neurons in the MSN did not appear to respond to NGF. Adjacent 7-microns-thick sections stained with ChAT and NGF-R immunocytochemistry revealed that these markers are strictly colocalized in individual neurons in the MSN in controls and in both groups of experimental animals. Thus, mouse NGF profoundly influences the process of axotomy-induced retrograde degeneration in cholinergic BFMC neurons in primates. The in vivo effectiveness of mouse NGF on primate BFMC neurons suggests that mouse or human recombinant NGF may be useful in ameliorating the ACh dependent, age-associated memory impairments that occur in nonhuman primates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2269885 TI - Competitive interactions between neurons making axosomatic contacts in the leech. AB - Axons of lateral nociceptive (N) neurons in leech segmental ganglia wrap certain somata in adjacent ganglia but no somata in their own ganglion. In adults, the N neurons, which accurately regenerate axosomatic wrappings, can be induced to sprout in their own ganglion and wrap target homologues if the ganglion is isolated by cutting the nerve cord. Manipulations that denervate the new targets without injuring the lateral N cell, including focal lesions and protease injections into other N cells, also cause sprouting within 2-4 months. In contrast, cutting the lateral N cell's axons causes little or no sprouting within the ganglion without denervation. Therefore, denervation rather than injury accounts for sprouting within the ganglion. It is concluded that lateral N cells can wrap somata in their own ganglion that are homologues of their usual targets, but they are prevented from doing so by axonal wrappings from N cells in adjacent ganglia. PMID- 2269886 TI - Tactile roughness: neural codes that account for psychophysical magnitude estimates. AB - Hypothetical neural codes underlying the sensation of tactile roughness were investigated in a combined psychophysical and neurophysiological study. The stimulus set consisted of plastic surfaces embossed with dot arrays of varying dot diameter and center-to-center spacing. Human subjects explored each surface with the pad of the index finger and reported their subjective sense of roughness magnitude. The same surfaces were scanned across the receptive fields of cutaneous mechanoreceptive afferents in monkeys while recording the evoked action potentials. Hypothetical neural codes for roughness magnitude were computed from the neural response patterns and tested for their ability to account for the psychophysical data. The psychophysical results showed that subjective roughness magnitude is an inverted U-shaped function of dot spacing that peaks near 3.0 mm spacing, and that increased dot diameter produces decreased roughness sensations at all dot spacings. Hypothetical neural codes that do not bear a consistent relationship to roughness magnitude across all of these stimulus conditions can be rejected as the code for roughness. Four types of neural codes were considered. They were based on (1) mean firing rate, (2) general variation in firing rate, (3) short-term temporal variation in firing rate, and (4) local spatial variation in firing rate. Mean firing rate failed to explain the psychophysical results: surfaces that evoked the same firing rate often evoked very different roughness judgments. In contrast, neural codes based on firing rate variation, especially in slowly adapting afferents, account for the psychophysical results. PMID- 2269887 TI - Oligodendrocytes arrest neurite growth by contact inhibition. AB - We have used video time-lapse microscopy to analyze in vitro the interactions of growth cones of newborn rat dorsal root ganglion cells with dissociated young rat CNS glial cells present in the cultures at low density. To provide optimal conditions for neurite extension, cells were grown on laminin and in NGF supplemented medium. Our initial observation showed that there are 2 subpopulations of growth cones differing in their growth rate on laminin (averages of 12 and 45 microns/hr). When these growth cones encountered astrocytes, they maintained their normal configuration and growth velocity. They subsequently grew along or on top of astrocytes. In some cases, however, fast moving growth cones showed a slight reduction in their growth rate. When growth cones countered oligodendrocytes, however, firm filopodial contact was sufficient to induce a rapid and long-lasting arrest of the growth cone motility, often followed by a collapse of the growth cone structure. One third of the paralyzed growth cones were observed to retract. Growth arrest and growth cone collapse were strictly dependent on membrane contact between neurons and oligodendrocytes. This contact inhibition phenomenon was exclusively found with differentiated oligodendrocytes and could be prevented by the monoclonal antibody IN-1 directed against neurite growth inhibitors NI-35 and NI-250 (Caroni and Schwab, 1988b). These results confirm previous findings that the neurite growth inhibitor proteins are important in axon outgrowth. Further, the inhibition of neurite growth exerted by oligodendrocytes is a contact-mediated phenomenon that can be triggered by the tip of growth cone filopodia. PMID- 2269888 TI - Immunocytochemical localization of the erythroid glucose transporter: abundance in tissues with barrier functions. AB - We investigated the cellular localization and tissue distribution of the glucose transporter protein in the nervous system of the monkey and rat, and in other tissues of the rat, by immunocytochemical methods with monoclonal and polyclonal antibodies to the glucose transporter of human erythrocytes. We found intense immunostaining, indicating a high density of the glucose transporter, in all intraparenchymal blood vessels of the brain and spinal cord, in pial vessels, and in endoneurial capillaries of peripheral nerves, nerve roots, and dorsal root ganglia. Larger blood vessels at the base of the brain and in major fissures did not stain. The only intraparenchymal brain microvessels that did not immunostain were in circumventricular organs. There was no specific immunostaining of neurons or glia, except for tanycytes in the floor of the third ventricle, which immunostained intensely. Vessels of the choroid plexus did not stain, but the choroid epithelium, especially its basal membranes, stained. The only non-neural organ where immunostaining was evident in its microvessels was the testis. In addition to the endothelium of neural and testicular tissues, there was immunostaining in certain epithelial tissues, such as the perineurium of peripheral nerves and nerve roots, the epithelium of the ascending loop of Henle in the kidney, and the epidermis of the skin. Based on these findings, we hypothesize that a high density of the erythroid-type glucose transporter is inherent to many endothelial and epithelial cells that are joined by occluding junctions. However, other epithelial tissues with known occluding intercellular junctions that lack the erythroid-type of glucose transporter may have other types of glucose transporter proteins. PMID- 2269889 TI - The neural site of binocular rivalry relative to the analysis of motion in the human visual system. AB - Neural processing is disrupted during suppression phases of binocular rivalry, as evidenced by the temporary invisibility of an otherwise complex, high-contrast visual stimulus. This paper investigates the locus of this disruption relative to the processing of information about image motion. In one experiment, observers tracked binocular rivalry between a stationary textured field and a plaid composed of 2 drifting cosine gratings, with the angle between components varied to produce different pattern speeds. (Plaid speed is given by the ratio of the component speed to the cosine of the angle between the 2 directions of motion.) Predominance of the moving plaid increased with pattern speed, even though the speed of the individual components remained constant. Control measures verified that this influence of plaid speed was not attributable to specific component orientations. Information about coherent motion influences the rivalry process, implying that the site of coherent motion analysis, presumably the middle temporal area (MT), received input during dominance phases of rivalry. A second experiment investigated the effect of suppression on the processing of complex, nonlinear motion. Observers tracked rivalry phases for a rotating spiral, then indicated the duration of the subsequently perceived spiral aftereffect (SAE) for both rivalry and nonrivalry conditions. The SAE was reduced when adaptation occurred under the rivalry condition, with aftereffect duration proportional to the total duration of spiral visibility during adaptation. Earlier work places rivalry after the site of the linear motion aftereffect, and the present results show that rivalry suppression occurs prior to the site of spiral motion processing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269890 TI - Effect of reinnervation on the degradation rate of junctional acetylcholine receptors synthesized in denervated skeletal muscles. AB - Two populations of ACh receptors (AChRs) with different degradation rates have been shown to coexist in the postsynaptic membrane after denervation of the neuromuscular junction (NMJ). One population, consisting of the slowly degrading original AChRs inserted into the plasma membrane prior to denervation, has a degradation half-life (t1/2) of approximately 8 d. This degradation rate accelerates after denervation (to a t1/2 approximately 3 d), but can be decelerated back to the predenervation rate by reinnervation. The second population, the rapidly degrading new AChRs, which replace the degrading original AChRs at the NMJ after denervation, resembles embryonic AChRs, with a t1/2 of approximately 1 d. In the present study, we report that the degradation rate of these new junctional AChRs is unaltered for 3-6 half-lives after reinnervation. We further report that a small amount (less than 10%) of slowly degrading AChRs (t1/2 approximately 3 d) may also be synthesized in denervated muscle. We suggest that, unlike its effect on the original, slowly degrading AChRs, reinnervation does not modulate the degradation rate of the rapidly degrading new junctional AChRs. It merely regulates the ratio of rapidly to slowly degrading AChRs being synthesized and inserted at the NMJ. PMID- 2269891 TI - Appetitive feeding behavior of Aplysia: behavioral and neural analysis of directed head turning. AB - The appetitive phase of feeding behavior in Aplysia consists of a behavioral sequence in which the quiescent animal starts to locomote and then assumes a characteristic feeding posture. In this position, head-turning responses can be elicited by a localized food stimulus (seaweed) delivered to the lips or tentacles. In response to brief (open loop) stimulation with seaweed, the animal turns toward the stimulus but greatly overshoots the target. However, the angular velocity and the final turning angle are a function of the eccentricity of the stimulus, progressively increasing with greater eccentricities. In a food-aroused animal, a brief tactile stimulus evokes turning and biting responses similar to those triggered by seaweed, which provides both tactile and chemical stimulation. Upon repeated tactile stimulation, however, the response magnitude decrements rapidly, whereas the magnitude remains high when turning responses are repeatedly elicited by food stimuli. A purely chemical stimulus sometimes can elicit a turning response, but chemical stimuli alone are much less efficacious than tactile stimuli alone. When the stimulus is maintained in a stationary position (closed loop), the animal turns until its mouth is oriented over the food. A turning response to a lateral stimulus can be reduced by an immediately following medial stimulus. To explain the above findings, we propose a form of response substitution, in which the response to the first, lateral stimulus is substituted by a weaker response to a more medial stimulus. No turning response is evoked when the animal is stimulated while performing spontaneous or evoked bites, though biting per se does not interrupt ongoing turning movements. In animals with lesions of the cerebral-buccal connectives, a food stimulus on the mouth is also followed by a reduction of the capacity of stimuli to elicit turning responses. In these lesioned animals, the food stimulus appears to elicit a bite command, though the biting behavior itself does not occur. Thus, it appears that the bite-related gating of stimuli is of cerebral origin, rather than due to the generation of the buccal motor program. The force necessary to power the turning movements was calculated from the trajectories of the movements. The results indicate that a power phase during the first half of the duration of the total movement is sufficient to generate a turn. The power phase can be followed by a brief gliding phase, and finally the movement appears to be actively terminated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2269892 TI - Pioneer growth cone steering decisions mediated by single filopodial contacts in situ. AB - In grasshopper embryo limb buds, the sibling Ti1 pioneers are the first neurons to initiate axonogenesis. The pioneer growth cones migrate from the limb tip to the CNS along a in direction comprising discrete steering events. Filopodial exploration of the cellular terrain in the vicinity of the advancing growth cone appears to be important for steering. Some information is available on the identity of cells and cell types, on cell-surface characteristics, and on the involvement of basal lamina in these steering decisions. In the work reported here, we have used computer-enhanced fluorescence video microscopy to examine filopodial behavior and the process of growth cone migration and reorientation resulting from interactions with the normal guidance cues on the in situ substrate. We observed several different kinds of migration and steering events, which appear to be related to the absolute and relative affinities of the contacted substrates. On a relatively homogeneous substrate of intrasegmental epithelium, growth cones advance by extending veils between filopodia, as is commonly observed on uniform substrates in vitro. Where growth cones confront an orthogonal border between substrates of dissimilar affinity, they remain on the higher-affinity substrate by extending new branches along it. Subsequently, reorientation in the preferred direction on the higher-affinity substrate is accomplished by regression of branches extended in the nonselected direction. By contrast, a single filopodial contact with a very high-affinity substrate, such as a guidepost neuron, can reorient a growth cone, even when it is migrating on a favorable substrate. In this situation, the filopodium that contacts the high affinity substrate expands in diameter until it becomes the nascent axon. PMID- 2269893 TI - The formation of terminal fields in the absence of competitive interactions among primary motoneurons in the zebrafish. AB - To make specific synaptic connections, projection neurons extend neurites to regions containing appropriate targets, then form synapses with the correct type and number of target cells. To investigate the mechanisms controlling this process, we have studied the formation of motoneuronal terminal fields in live zebrafish embryos. The primary motoneurons of the zebrafish are identifiable as individuals and innervate neighboring but mutually exclusive territories. To study the first week of their development, which includes embryonic and early larval stages, we labeled identified motoneurons with fluorescent dyes and made sequential observations of the axonal branches of individual neurons. We assessed the roles of competitive interactions and synapse elimination in the formation of specific synapses by identified neurons that innervate neighboring territories. Our results demonstrate that primary motoneurons establish their cell-specific terminal fields primarily by directed outgrowth of branches and formation of neuromuscular junctions almost exclusively on appropriate muscle fibers, rather than by overproduction and selective elimination of inappropriate branches. Retraction of the few branches that are inappropriately placed, though correlated in time with the ingrowth of branches from appropriate motoneurons, occurs independently of the influences of these other cells and when neuromuscular transmission is blocked. We suggest that, similar to the way in which they pioneer peripheral nerve pathways, primary motoneurons establish their cell specific terminal fields using mechanisms that operate independently of activity and competition. The target or substrate interactions that are likely to instruct directed growth-cone navigation may be similar to the interactions that determine the locations of territorial borders and that instruct the retraction of misplaced branches. PMID- 2269894 TI - Kainic acid on neostriatal neurons intracellularly recorded in vitro: electrophysiological evidence for differential neuronal sensitivity. AB - The electrophysiological effects produced by different concentrations of kainic acid (KA) were studied by utilizing intracellular recordings from neostriatal slices. In most of the recorded cells (81%), concentrations of KA ranging between 10 and 300 nM produced reversible and dose-dependent membrane depolarizations. Higher concentrations of this agonist caused larger depolarizations and changes of the membrane properties of the recorded neurons not reversible during the time of recording. In a smaller percentage (19%) of the recorded cells, 10-100 nM KA did not produce significant membrane depolarizations; in these neurons, the depolarizations produced by higher concentrations of KA were small and reversible. The 2 populations of neurons showed similar electrophysiological properties and did not reveal differential sensitivity to quisqualic acid (QUIS; 10-30 microM) or to NMDA (10-30 microM). Tetrodotoxin (TTX; 1 microM) did not reduce the depolarizations produced by KA and by NMDA. Low-calcium, cobalt containing solutions abolished the effects produced by NMDA, but not the KA induced depolarizations. Kynurenic acid (500 microM) significantly antagonized the depolarizations produced by KA and reduced the changes of the membrane properties caused by high doses of this agonist. In several neurons, KA induced bicuculline-sensitive synaptic depolarizing potentials. Our findings suggest the presence of 2 subpopulations of neostriatal neurons showing differential postsynaptic sensitivity to KA. The differential sensitivity of neostriatal neurons to KA might influence the responses of these cells to glutamatergic cortical inputs and the degenerative changes observed in neostriatal neurons in some pathological conditions. PMID- 2269896 TI - Dominican concepts of health and illness. AB - It is essential that primary health care providers be familiar with the cultural surroundings from which a person emerges. The Dominican immigrants, like all immigrants, bring with them a whole value and belief system concerning health, illness, and disease prevention. Through a better understanding of that belief system, the primary health care provider can offer a more meaningful interaction with the Dominican immigrant population. PMID- 2269895 TI - Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. AB - We have used Golgi-impregnated tissue to demonstrate that apical dendritic spine density in CA1 hippocampal pyramidal cells undergoes a cyclic fluctuation as estradiol and progesterone levels vary across the estrous cycle in the adult female rat. We observed a 30% decrease in apical dendritic spine density over the 24-hr period between the late proestrus and the late estrus phases of the cycle. Spine density then appears to cycle back to proestrus values over a period of several days. In contrast, no significant changes in dendritic spine density across the estrous cycle occur in CA3 pyramidal cells or dentate gyrus granule cells. These results demonstrate rapid and ongoing dendritic plasticity in a specific population of hippocampal neurons in experimentally unmanipulated animals. PMID- 2269897 TI - Breaking away: how District 16, New York State Nurses Association got started. AB - This paper will describe the series of events from 1938-1942 that led to the creation of a new district for nurses in Westchester County. Historical data on the context of nursing are included. Primary sources from the archives of NYSNA District 13 and 16 provided the background information. In addition, selected oral history interviews provided data for the narrative, which is primarily of a descriptive nature. PMID- 2269898 TI - A Rehnquistean bed: the abortion issue revisited. AB - Individuals as members of societies are subject to externally imposed norms of behavior (laws). When societal control and regulation adversely impact upon individual autonomy, conflict is frequently the end product. Such issues surround the rights of privacy vis-a-vis the abortion issue. The Supreme Court addressed this issue in the 1988-1989 term. This article critically examines the court's decision and raises questions of individual and professional import. PMID- 2269899 TI - Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (TB). AB - Current surveillance data indicate that the spread of human immunodeficiency virus (HIV) infection has increased the risk of Mycobacterium tuberculosis (TB). After years of decline, in 1986, the Centers for Disease Control (CDC) reported a 2.6% rise in the number of cases of TB. The dual diagnosis of TB and HIV infection is being reported more frequently, especially among the inner city poor, racial and ethnic minorities, and intravenous drug users. Nurses need to be aware that intradermal tuberculin testing may be unreliable in HIV infected persons and that monitoring for treatment compliance may be difficult. Additionally, nurses should be aware of guidelines to minimize the potential for occupational exposure and the need for reporting all new cases and non-compliant persons to local health departments. PMID- 2269900 TI - Surfactant replacement therapy. PMID- 2269901 TI - Vibroacoustic stimulation can pose risks. PMID- 2269902 TI - Umbilical artery Doppler flow studies during pregnancy. AB - The fetus depends upon adequate uteroplacental blood flow for normal growth and development. Inaccessibility of the fetus has made assessment of uteroplacental blood flow difficult. Doppler ultrasound of umbilical artery blood flow provides a noninvasive method for assessing pregnancies at risk for poor outcomes. This article describes blood flow studies using the Doppler ultrasound technique and provides related nursing implications. PMID- 2269903 TI - Birth defect prevention. Nursing interventions. AB - Nurses who are knowledgeable about the principles of teratology can effectively assist families in preventing neonatal malformation and dysfunction. A review of the history and development of the field of teratology, related research purposes and methods, a list of currently known teratogenic agents, and recommendations for nursing interventions for primary and secondary prevention are provided. PMID- 2269905 TI - The use of Orem's self-care model in the neonatal intensive-care unit. AB - This article gives an overview of Dorothea Orem's self-care model and discusses the newborn's potential for self-care. A case presentation is provided to demonstrate the applicability of the model in the neonatal intensive-care unit. PMID- 2269904 TI - Patients' prenatal medical record precis. AB - A prenatal assessment form for ambulatory prenatal patients was designed to provide information required for effective patient care during unscheduled visits or for visits with health-care providers unfamiliar with a patient's history. The abbreviated record enables health-care providers to manage problems before obtaining complete medical records from centralized sources. In two years of use, these abbreviated records have improved both the efficiency and quality of care for unscheduled and scheduled visits. PMID- 2269906 TI - The use of fundal pressure during the second stage of labor. AB - The intensity of the legal climate and the focus on standards of practice in the obstetric setting have forced nurses to carefully scrutinize clinical techniques. The use of fundal pressure during the second stage of labor is a cause of great concern for many obstetric nurses. A nationwide pilot study was conducted to determine whether fundal pressure application is an accepted part of nursing practice in contemporary obstetrics. Sixty-two of the respondents (84%) used fundal pressure during the second stage of labor in their institutions. PMID- 2269907 TI - Mothers' perceptions of breast milk. AB - In-depth interviews were conducted with nine breastfeeding mothers to examine their attitudes related to breast milk. Participants revealed that variations in the quantity of milk produced were closely monitored and that some mothers were concerned about changes in the quality of their milk. Differences in perceptions of factors that influence quality and quantity of milk production are described. Changes in a variety of interventions aimed at supporting and maintaining breastfeeding are suggested in light of these findings. PMID- 2269908 TI - Cell-constituent polyamines in Candida species and new biotyping of Candida albicans, Candida tropicalis and Candida parapsilosis strains. AB - Intracellular amines from three Candida species were extracted and chemically derivatized by a modification of the Seiler procedure. The results of qualitative determinations of 13 amines in 20 strains each of Candida albicans, Candida tropicalis and Candida parapsilosis are presented. This report is the first to describe the detection of amines other than the classical spermine, spermidine, putrescine and cadaverine in yeasts and fungi. Characteristic profiles due to the presence or absence of particular amines in the Candida species studied are demonstrated. Although these could not be used as strict differential markers at the species level, biotyping schemes based on amines are proposed to differentiate strains of C. albicans, C. tropicalis and C. parapsilosis. PMID- 2269909 TI - Interaction of Candida albicans with murine gastrointestinal mucosa from methotrexate and 5-fluorouracil treated animals: in vitro adhesion and prevention. AB - The aim of the present study was to investigate whether the cytotoxic anti-cancer drugs methotrexate (MTX) or 5-fluorouracil (5FU), which affect the gastrointestinal (GI) mucosa, would also affect the ability of the damaged mucosa to bind the GI commensal yeast Candida albicans. ICR conventional female mice were treated with intraperitoneal (IP) MTX (3 mg per mouse, or intravenous (IV) 5FU (200 mg kg-1 body weight). On various days post-treatment, the small intestine was removed, tissue disks prepared and exposed for 2 h to radiolabeled C. albicans. The percent adherence of the fungus to the mucosa was assayed by determining the counts per minute (c.p.m.). An increase in the in vitro adherence of C. albicans to murine GI mucosa was found posttreatment with MTX or 5FU. The maximal increase (net increase of 40-50%) was observed on days 3-4 post-treatment with MTX or 5FU, concurrently with the maximal decrease in the total number of white blood cells (WBC) and loss in spleen weight of the treated animals (indicators of cytotoxicity of these drugs). In addition, experiments to block Candida adherence with chitin soluble extract (CSE), an inhibitor used in previous studies, were also carried out. CSE inhibited the adherence of C. albicans to the damaged GI mucosa, as well as to the GI mucosa from normal untreated mice, by up to 64% approximately. Based on these results and on findings from our previous study investigating the adherence of C. albicans to GI mucosa from irradiated mice, it can be concluded that increased adherence of C. albicans to the GI mucosa may occur in patients post-anti-cancer therapy (irradiation, or chemotherapy). This observation may partially explain the high tendency of these debilitated patients to develop systemic candidosis. Further experiments to study adherence of C. albicans to gut mucosa in vivo and eventually to inhibit this adherence with CSE are currently in progress in our laboratory. PMID- 2269911 TI - Cross-infection and diversity of Candida albicans strain carriage in patients and nursing staff on an intensive care unit. AB - Colonization of patients and nursing staff on an intensive care unit by Candida albicans was studied over a 4-month period. Multiple swabs and samples were taken from patients and their nurses on 12 occasions during the study period. During this study there were no obvious clinically relevant candidal infections. Patients yielded C. albicans from at least one body site on 68%, and nurses on 57% of occasions. All isolates of C. albicans were further characterized by both morphotyping and resistotyping. All patients but one were colonized by a single strain throughout their stay on the unit, whereas nurses were often colonized by more than one strain type. Strains isolated from nurses' hands were all indistinguishable from strains colonizing the patient under their care, whilst strains isolated from nurses' mouths were usually distinct from their patients'. The probability that a C. albicans culture positive nurse carried an indistinguishable strain from that of her positive patient was p = 0.632, compared with p = 0.325 that a randomly chosen positive nurse would carry a strain indistinguishable from that of a randomly chosen positive patient. Diversity in patients' strains was low (D = 0.667) compared with nurses' strains (D = 0.778). These results suggest that cross-infection by C. albicans is a common occurrence on intensive care units. The reason outbreaks of candidal disease are not more common may be related to differences in virulence of the strains. PMID- 2269910 TI - An extended QBASIC program for the normalization and computation of whole-cell protein profiles and the application to clinically important Candida species. AB - The computer program described enables a rapid calculation of relative molecular masses of proteins from different yeasts and microbial pathogens, by interpolation from a molecular weight calibration curve that comprises stepwise linear regression between the protein bands produced by the internal standards. A similarity matrix can then be produced, taking into account variations between calculated molecular masses caused by small differences in bandwidths and/or positions of specific protein bands. This program has been applied to different Candida species and the similarity data obtained further analysed numerically utilizing CLUSTAN II on a SPERRY 1100 multi-processor. PMID- 2269912 TI - Periodontal repair in dogs: effect of wound stabilization on healing. AB - This study evaluated a biodegradable polylactic acid matrix as a wound stabilizing implant in reconstructive periodontal surgery. Supra-alveolar circumferential periodontal defects, 5 to 6 mm large, were surgically created around the mandibular premolars in 7 beagle dogs. The root surfaces in left and right jaw quadrants were treated with either heparin or saline. In this model, root surface treatment with heparin compromises periodontal repair and results in a long junctional epithelium and a reduced connective tissue repair to the root surface, whereas saline treatment results in almost complete connective tissue repair. Following heparin or saline treatment a polylactic acid implant was placed on 1 premolar in each quadrant. After 4 weeks of wound healing, the dogs were sacrificed and tissue blocks prepared for histometric analysis. Postoperatively, the implant became exposed and infected in 3 dogs and had to be removed. Therefore, the results reflect the 4 dogs in which healing progressed uneventfully. Connective tissue repair to the root surface in teeth treated with heparin averaged 82% of the defect height. Mean connective tissue repair in teeth treated with heparin and the implant was significantly greater and comprised approximately 99% of the defect height (P less than 0.05). Teeth treated with saline either with or without the implant also healed with almost complete connective tissue repair. The results support the importance of wound stabilization in periodontal wound healing. Development of biodegradable implant systems aimed at stabilizing and supporting the healing wound seems a desirable direction for future research in regenerative periodontal procedures. PMID- 2269913 TI - Increase of interproximal bone density after subgingival instrumentation: a quantitative radiographical study. AB - Ten interproximal sites, with periodontal pockets deeper than 5 mm and showing loss of bone on standard dental radiographs, were treated by subgingival instrumentation in 10 patients properly motivated and given thorough hygiene instructions. The index of gingival inflammation, the plaque index, the degree of mobility, the depth of the pockets, and the loss of attachment were measured before starting the treatment, and 2 months, 6 months, and 1 year after treatment. Standardized reproducible radiographs of the 10 sites were taken by using a recently developed paralleling instrument before treatment, immediately after and 2 months, 6 months, and 1 year afterwards. The density of the interdental bone was measured on the radiographs by a computer assisted densitometric technique at three levels of the interdental septum: the most occlusal or "superficial" level; the "deep" level, arbitrarily chosen 1.5 mm below; and the "control" level, in a much deeper area of interproximal bone. As further control, the density of the superficial crestal bone was also followed in 5 healthy untreated sites from 5 of the patients. As expected, a significant improvement of the clinical parameters was observed during the year following therapy. The results of the radiographical analysis showed statistically significant increases of both the superficial and deep average densities of interproximal bone at 6 months and 1 year after treatment. The superficial bone density was, on the average, 13% higher at 6 months and 16% higher at 1 year, as compared to that measured immediately after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269914 TI - Clinical evaluation of a biodegradable collagen membrane in guided tissue regeneration. AB - A bio-resorbable type I collagen membrane was investigated as a barrier for guided tissue regeneration. Ten human subjects with at least one pair of contralateral periodontal lesions with probing pocket depths of greater than or equal to 5 mm and radiographic evidence of greater than or equal to 40% bone loss were included. Each patient underwent contralateral surgical flap procedures. A collagen barrier was adapted to the tooth in the experimental defect and the flap replaced and sutured. The controls consisted of the same procedure without the placement of the barrier. Standardized measurements of change in probing attachment levels and fill of intrabony defects were obtained at the time of surgery and 1 year later at the time of surgical re-entry. The differences in change of probing attachment levels and amount of bone fill between individual test and control sites were compared utilizing the student's t-test for paired samples. The mean probing attachment gain in the test sites was 0.56 +/- 0.57 mm, and there was a mean probing attachment loss of 0.71 +/- 0.91 mm in the control sites (P less than 0.01). The gain of bone in test lesions was 1.16 +/- 0.95 mm, while no gain was observed in the control lesions (P less than 0.01). The results of this study demonstrated that sites treated with a collagen barrier comprised of cross-linked bovine Type I collagen exhibited significantly better healing as compared to control sites over the 1-year period of the study. PMID- 2269915 TI - A Veterans Administration Cooperative Study of biphasic calcium phosphate ceramic in periodontal osseous defects. AB - One hundred thirty-seven V.A. patients were randomized to one of three treatment groups to evaluate the efficacy of biphasic calcium phosphate (BCP) ceramic in the treatment of periodontal osseous defects. This material was tested against both autogenous bone implant and open flap curettage procedures. Baseline probing attachment level, Navy plaque index, and gingival index were recorded for all patients. These parameters were monitored for 3 years. At the end of this period, 101 patients had completed the study. Although the plaque and gingival indices steadily increased with time, there were no statistically significant differences among the treatment groups. Patients in the ceramic group had a gain in attachment level of 1.0 mm; those in the curettage group, 0.9 mm; and 0.4 mm for those in the bone implant group. Although the BCP patients had a greater gain, the difference was not statistically significant. In this veteran population, not only did BCP patients fail to outperform those in the control groups, all three treatment groups were similarly ineffective. PMID- 2269916 TI - Early-onset periodontitis: radiographic patterns of alveolar bone loss in 55 cases from a selected Malaysian population. AB - The objective of this report was to determine the radiographic patterns of alveolar bone loss in early-onset periodontitis (EOP) cases in a selected Malaysian population. The radiographs of 55 cases of EOP patients were examined and the radiographic patterns were classified as follows: Type I: bone destruction on first molars and/or incisors only; Type II: bone destruction on first molars and/or incisors and several additional teeth (less than 14 teeth); Type III: generalized bone destruction (greater than 14 teeth), but with involvement noticeably more extensive on the first molars and/or incisors; Type IV: generalized bone destruction (greater than 14 teeth), but with no more bone loss on the first molars and/or incisors than on other involved teeth. Sex, age, and missing teeth were also recorded. Out of 55 cases, 47 cases, 22 males and 25 females, were classified into the types mentioned above; the remaining 8 cases were excluded due to too many missing teeth. It was found that 7 (14.9%) were Type I; 12 (25.5%) were Type II; 7 (14.9%) were Type III; and 21 (44.7%) were Type IV. There was a predominance of first molar/incisor involvement in Types I, II, and III with the maxillary first molars most frequently involved followed by the mandibular central incisors. Type I occurred in the younger age group and Types II, III, and IV mainly in the older age group. It was concluded that EOP in this patient sample resembled that of western society. PMID- 2269917 TI - Oxidized cellulose mesh used as a biodegradable barrier membrane in the technique of guided tissue regeneration. A case report. AB - In this case study oxidized cellulose mesh was shown to have potential for use as a biodegradable barrier membrane for regenerative procedures in furcation areas and interdental infrabony defects. The material was customized so as to protrude coronally to the soft tissue flaps and interdentally after surgery. The material resorbed and normal healing took place with crevicular depths less than 2 mm by 1 month postoperatively. By 6 months postoperatively, 2 of the sites showed crevice depths of 3 mm. Initially there was negligible recession, except in one site, but by 6 months after surgery some resistant to probing. It is, therefore, concluded that this material may have the potential for use as a biodegradable membrane in the technique of guided tissue regeneration. PMID- 2269918 TI - Necrotizing ulcerative gingivitis and cancrum oris (noma) in Ibadan, Nigeria. AB - This study analyzed 58 cases of necrotizing ulcerative gingivitis (NUG) and 5 cases of cancrum oris among children who sought treatment at the Ibadan University College Hospital, Dental Centre in a 1-year period. The peak occurrence of NUG was among 4- and 5-year old children and 84.5% of them were in the 2 to 7 years age range. Seventy-two percent presented in the rainy season with positive history of recent febrile illness in 55 cases. There was no statistically significant association of NUG and rainy season. Possible predisposing factors in NUG and cancrum oris such as malnutrition, infectious childhood diseases, HIV infection, and immune compromise are discussed. It is suggested that children at risk should be advised to maintain good oral hygiene, adequate nutrition, and proper medical care. PMID- 2269919 TI - Compartment pressure in the foot. Analysis of normal values and measurement technique. AB - This clinical trial was carried out to verify the validity of the current objective compartment pressure parameters described in the forearm and leg for use in the foot. The authors evaluated the compartment pressures of the central plantar compartment in 25 normal volunteers (94 separate measurements). In addition to determining an average normal foot compartment pressure, two methods of measurement were compared. Results showed no significant difference in normal values through the use of an arterial line monitor technique (5.98 +/- 2.78 mm Hg [SD]) as compared with a Stryker intracompartmental pressure monitor (4.69 +/- 2.62 mm Hg [SD]). It was found that pedal edema caused a statistically significant increase in pressures. The authors propose a standard technique for pedal compartment pressure measurement and discuss diagnosis and management of compartment syndrome in the foot. PMID- 2269920 TI - Fixation of the Austin procedure with the Herbert screw. A modified technique. AB - Although the Austin osteotomy is intrinsically stable, some surgeons use fixation to enhance stability. One form of fixation that may be used for this procedure is the Herbert screw. The author presents a modification of a previously reported technique, and describes it as a five-step process. The advantages and potential disadvantages of the use of the Herbert screw with the presented technique are discussed. PMID- 2269921 TI - Diagnosis of deep vein thrombosis using real-time B-mode ultrasound imaging. AB - The authors discuss real-time B-mode imaging in reference to the diagnosis of deep vein thrombosis. This technique is noninvasive, reproducible, painless, and accurate in diagnosing deep vein thrombosis. A case report demonstrating the effectiveness of this modality is presented. The authors believe this diagnostic tool will soon become the procedure of choice in the diagnosis of deep vein thrombosis. PMID- 2269922 TI - Os trigonum. Variation of a common accessory ossicle of the talus. AB - The authors present a pictorial essay showing the range of variability of separate and attached os trigona in dry-bone specimens. The presence of free os trigona is found to be 1.7% in an early 20th-century skeletal sample, with no findings of the trait in 513 tali of prehistoric native Americans and Eskimos. PMID- 2269923 TI - Foot deformities in Apert's syndrome. Review of the literature and case reports. AB - Two cases of Apert's syndrome (acrocephalosyndactylism), demonstrating typical foot pathology, are presented. A review of the pertinent literature is included, and the new focus on early corrective foot surgery is discussed. PMID- 2269924 TI - Silver sulfadiazine and hydrocortisone cream 1% in the management of phenol matricectomy. AB - The phenol matricectomy is one of the most common procedures performed in the podiatrist's office. Since a chemical burn is produced, correct care of the wound is essential. The authors studied the use of silver sulfadiazine, hydrocortisone cream, and a mixture of the two, on wounds resulting from phenol matricectomy procedures. The study shows that when silver sulfadiazine and hydrocortisone are used in combination, some of the usual sequelae seen with phenol matricectomies are markedly reduced and wound healing progresses at a more rapid rate with less complications. PMID- 2269925 TI - Squamous cell carcinoma of the great toe in a black man. PMID- 2269926 TI - Recurrent rheumatoid nodule of the foot. PMID- 2269927 TI - Research process. Planning the research project. AB - This second article in a series of six on the research process provides a guide to planning a research project from start to finish. By description and illustration, 13 steps are outlined. Although the guide is comprehensive, advice is offered at strategic points regarding the value of consulting with a research specialist or a colleague experienced in research to gain assistance or insight into the planning process. Additionally, an admonition underlies the whole process: keep it simple and succinct. PMID- 2269928 TI - [Gingival thickening with a submerged connective tissue graft]. AB - Gingival thickness is a clinical characteristic which should be given more consideration in evaluating muco-gingival problems. It is proposed that thick gingiva prevents gingival recession and is of particular significance when fixed prosthesis is being employed. The technique outlined includes a connective graft from the lamina propria of the palatal mucosa into the gingival connective tissue. A case report documents the technique. PMID- 2269929 TI - [Basement membrane in adult and juvenile/post-juvenile/periodontitis: an ultrastructural study]. AB - Soft tissue changes in the pocket wall in the various forms of periodontitis were studied on an ultrastructural level in 20 patients. Considerable differences were noticed according to the degree of inflammation and severity of the periodontitis. PMID- 2269930 TI - [Efficiency of a new instrument: the Jet-Floss for the elimination of dental plaque]. AB - A study was undertaken to compare the efficiency of a manual toothbrush, unwaxed dental floss, a traditional water irrigating device and a new instrument, the Jet Floss, in regard to dental plaque removal. The ability to remove 48 hours plaque was assessed among the oral hygiene techniques. The Jet-Floss method was found to be superior in the pericoronal areas than other form of instrumentation. The combined oral hygiene exercise utilizing the conventional toothbrush and the Jet Floss yielded significantly better results than the use of each single device. PMID- 2269931 TI - [In vitro study of the cytocompatibility of 3 biological glues]. AB - Human derived fibrin glues are being used with increasing frequency in periodontal surgery. Three different fibrin glues were tested in an in vitro system for gingival fibroblast proliferation. The results show a cytocompatibility of these products which justifies their employment in periodontal therapy. PMID- 2269932 TI - [Regenerative therapy of interradicular lesions. Review of the literature]. AB - The short and mid-term regenerative therapy in the furcation lesions seems to be promising. The aim of this review is to describe different technics used today. The limits of this therapy, the gain of bone level and/or gain of attachment level and the complementarity of their biological principles are discussed. PMID- 2269933 TI - [Noma. Apropos of a case in a 10-year old child]. AB - The author reports an unusual case of Cancrum Oris in a young nomadic Moroccan patient. They attribute the presence of this condition to poor dental oral care and the neglect of the disease in its early stages. Cancrum Oris can result in oral and facial mutilitations and on some occasions, death. It is proposed that preventative measures, including exemplary oral hygiene and adequate nutrition during infancy and childhood could eradicate the disease. PMID- 2269934 TI - Immunopathogenesis of oral lichen planus. AB - Oral lichen planus (LP) is a common mucosal disorder in which cell mediated immunity is thought to play a major role. In this paper, a unifying hypothesis which attempts to integrate cellular and molecular signals in the local immune response in oral LP is presented. In this model, modified keratinocyte surface antigens are the target for the cytotoxic cell response which characterizes oral LP, whereas mast cells and antigen presenting Langerhans cells are key cellular elements in the evolving lesion. It has been established that mast cell degranulation induces adhesion molecule expression on endothelium which facilitates lymphocyte homing to the tissues. These adhesive interactions between lymphocytes and keratinocytes are postulated to be important determinants in the effector phase of the lesion. Cytokines produced by both lymphocytes and keratinocytes which influence the local immune response could promote chronicity. Accordingly, modulation of immunologic events is a potential therapeutic approach for oral LP. PMID- 2269935 TI - Expression of c-erbB2 and c-myc in squamous epithelia and squamous cell carcinomas of the head and neck and the lower female genital tract. AB - Normal tongue and cervical mucosa, premalignant cervical and vulvar lesions, primaries and metastases of squamous cell carcinomas from the oral, laryngeal, cervical and vulvar mucosa were analyzed for c-erbB2 and c-myc transcription with northern-blots using 32P single-stranded RNA probes. Transcription of c-erbB2 and c-myc could be detected for almost all tissues including normal samples. A slightly enhanced transcription level was found in three cervical intraepithelial neoplasias of Grade III (CIN III) but in none of the malignant lesions. Increased transcription of c-myc was observed in premalignancies and malignancies. It was more frequent in oral and laryngeal squamous cell carcinomas (SCC) (8 of 9 cases) than in genital SCC (3 of 11 cases) or premalignancies (3 CIS of 14 CIN/VIN). No relationships of c-myc enhanced transcription level with tumor grading and staging were noticed. Thus, mere oncogene expression is a widespread phenomenon in tissues of different histogenesis and quantitative analysis is necessary prior to ascribe any diagnostic or prognostic relevance. Moreover, the frequency of tumors with enhanced transcription may vary for phenotypically closely related tumors of different organs. PMID- 2269936 TI - Oral intravascular papillary endothelial hyperplasia. AB - Intravascular papillary endothelial hyperplasia (IPEH) is usually a cutaneous lesion thought to represent a peculiar manifestation of an organizing thrombus. IPEH can be subdivided into a pure form that occurs within a dilated vascular space and a mixed form that appears as a focal change within a preexisting vascular lesion, such as hemangioma. The principle significance of the lesion lies in the fact that it may be mistaken for angiosarcoma. Oral lesions are uncommon and the present paper reports on 16 new cases of oral IPEH, analyzing their clinical and histomorphologic features. Histologically, 11 lesions appeared in a pure form and 5 lesions in a mixed form. Thrombi were detected in all but one case. The most common location was the lip, followed in decreasing frequency by the tongue and buccal mucosa. Local excision was the treatment of choice. PMID- 2269937 TI - Degenerative changes in masseter and temporalis muscles in limited mouth opening and TMJ ankylosis. AB - The masseter and temporalis muscles were studied ultrastructurally in eight cases suffering from restricted mouth opening and TMJ ankylosis. The changes varied from slight degeneration of muscle fibers, such as accumulation of lipid or lipofuscin deposits, Z-band streaming and derangement of myofilaments, in one case to moderate or severe changes of muscle atrophy and necrosis in the remaining seven cases. Nemaline bodies were also observed in one of these seven cases. In addition to these muscle changes neural degeneration especially of myelinated nerves were found in three of the cases studied. The present findings showed that in spite of the diversity of the underlying factors affecting the joint, there was many similarities in the changes observed within the muscle. It is postulated that these degenerative muscle changes probably play an important role in restricted mouth opening and TMJ ankylosis, and that some of these muscle pathology may be the result of neural involvement. PMID- 2269938 TI - Postnatal effects of nicotine on incisor development of albino mouse. AB - Young albino mice, 4-days-old, exposed to 0.1% nicotine sulfate on gestational days 6-20 were compared with untreated pups to determine nicotine's effects on the animals. Pregnant mice were given intraperitoneal injections of nicotine at a dose of 1.67 mg/kg/day. Data of pups weight, CRL, distance between the anterior and posterior limbs, maximum head height and width as well as head circumference were collected. The neonates were then decapitated, their entire mandibles were excised, routinely prepared, sectioned and stained with H and E for histologic examination of the developing incisors. All the parameters were significantly reduced in the treated group. Histologically, the processes of odontogenesis appeared retarded in nicotine treated animals, whereas the control group demonstrated normal dentin and enamel formation. Thus nicotine has a detrimental effect on the development of newborn offspring in general and incisor development in particular. This effect begins prenatally and extends postnatally. PMID- 2269939 TI - A variant of calcifying epithelial odontogenic tumor with Langerhans cells. AB - A variant of calcifying epithelial odontogenic tumor (CEOT) with Langerhans cells is reported. Compared to a typical CEOT, the tumor islands of this case were thin and composed of a small number of polyhedral epithelial cells. Almost no calcification of homogeneous eosinophilic materials was observed. In addition, clear cells which structurally corresponded to Langerhans cell were intermingled in the epithelial islands. These cells stain positively for S-100 protein, lysozome, MT 1, LN-3 and OKT 6 antibodies, but not for keratin antibody. Electronmicroscopic examination revealed the rod-shaped and racket-shaped structures called Birbeck's granules in the cytoplasm of these clear cells. Our observations indicate a variant case of CEOT with Langerhans cells in tumor nests. PMID- 2269940 TI - SEM contribution to the morphological study of dental structures in ovarian cystic teratoma. AB - This study in scanning electron microscopy (SEM) was carried out to observe the possible pathologic aspect of five teeth grossly arranged in normal sequence and of their surrounding tissues, found inside an ovarian cystic teratoma. Though the general morphology of the teeth was nearly normal, several anomalies affected the different mineralized dental tissues such as enamel hypoplasia, irregular growth of cementum, altered predentin layer, and immature osteofibrous bony outgrowths. PMID- 2269941 TI - Dinner conversation. Meal therapy to differentiate eating behavior from family process. PMID- 2269942 TI - What really happened? Incidence and factor assessment of abused children and adolescents. AB - Abuse of children and adolescents is a societal problem. If health-care providers are to intervene adequately in abuse, they must identify the occurrence, elicit all pertinent information surrounding the abuse and the patient's response, and integrate pertinent abuse issues in the overall treatment plan for the patient. This study has conclusively demonstrated the failure of health-care providers to assess and plan treatment based on the comprehensive documentation of sexual and physical abuse factors. Findings clearly indicate a need for education of health care providers in the development of comprehensive and integrated treatment plans for abused psychiatric patients based on documentation of all factors related to trauma learning and replay. Service agencies must be willing to implement in service programs that provide nurses and other health-care providers with the cognitive and affective knowledge and skills necessary to feel comfortable in the management of abuse issues. PMID- 2269943 TI - How therapeutic is therapeutic holding? PMID- 2269945 TI - Does it make a difference? The effect of a women's issues group on female psychiatric inpatients. PMID- 2269944 TI - The use of therapeutic correspondence: creative approaches in psychotherapy. PMID- 2269946 TI - Drug firm not to blame for high AZT cost. PMID- 2269947 TI - Timely advice. PMID- 2269948 TI - Depression at work: costly but treatable. PMID- 2269949 TI - Easing the way: a multifaceted approach to day treatment. PMID- 2269950 TI - The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model). AB - Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269951 TI - Initial evaluation of variable graft lengths and lesion lengths in the repair of nerve gaps. AB - This experiment evaluated the electrical and histologic differences between two groups of rats, one of which underwent same-length bilateral resection of posterior tibial nerves prior to being repaired with grafts of different lengths, while the other group underwent different-length resections with same-length graft repair. In this rat model, 18 animals were used and divided into two groups. The first group of animals underwent bilateral resection of 8-mm segments of posterior tibial nerve. To repair these nerves, one leg received two 8-mm sural nerve grafts (Group A), while the other leg received two 16-mm sural nerve grafts (Group B). The second group of rats underwent posterior tibial nerve resections of 8 mm and 16 mm, respectively. The leg with the 8 mm of posterior tibial nerve resected, received two side-by-side 16-mm sural nerve grafts (Group C); the other leg with 16 mm resected, received two 16-mm sural nerve grafts (Group D). Electrophysiologic comparison of nerve conduction velocity for Groups A and B showed a significant difference (p less than 0.05), as did the same comparison for Groups C and D (p less than 0.05). Histologic studies showed that Groups A and D had marked extrafascicular escape of the regenerating nerve axons, disorganizational growth of minifascicles, and loss of integrity of the donor fascicles, while Groups B and C had very minimal extrafascicular escape of regenerating axons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2269952 TI - Electrophysiologic evaluation of peripheral nerve regeneration through allografts immunosuppressed with cyclosporin. AB - A model was designed to evaluate the long-term in vivo electrophysiology of rat peripheral nerve transplants. The application of this model was demonstrated using cyclosporin (CSA) immunosuppression of recipient animals to facilitate peripheral nerve regeneration through nerve allografts. Isogenic Brown Norway (BN) rats [RT1n] were divided into three groups: two received Lewis (LE) rat [RT1l] allografts and one received BN isografts. One allograft recipient group received CSA immunosuppression for the duration of the investigation (150 days). Successful nerve regeneration in the isograft and the immunosuppressed allograft recipient groups was determined by immunohistochemical methods and serial in vivo electrophysiologic techniques to measure nerve conduction velocity and evoked compound muscle action potential amplitude. Statistical analysis of these results indicate that: (a) CSA immunosuppression of peripheral nerve allograft recipients facilitates peripheral nerve regeneration which is indistinguishable from isograft recipient controls at the functioning axon level; and (b) in vivo electrophysiologic monitoring in this model is particularly useful for long term peripheral nerve transplantation studies permitting serial assessment of regeneration with little morbidity. PMID- 2269953 TI - Restoration of lymph drainage after extremity replantation. AB - A clinical analysis of 171 major extremity replantations was carried out. From one month to 2.5 years after surgery, direct lymphographic studies of replanted limbs were done in 17 patients (16 upper limbs and one lower limb). Despite a complete disruption of lymphatic drainage, replanted limbs underwent adaptive and compensatory structural changes of the lymphatic system in the post-replantation period; first, with regeneration of cutaneous vessels and then (after six to eight weeks postoperatively) with regeneration of lymphatic collecting vessels. Such changes led to improvement as early as four to six weeks postoperatively and subsequently to restoration of lymphatic drainage in the replanted limb. The rate and extent of lymphatic recovery depends largely on the surgical techniques used in replantation. PMID- 2269954 TI - Morphofunctional evaluation of fibrin glue versus microsuture nerve repairs. AB - Complications of microsuture repair of peripheral nerves include mechanical trauma, foreign body reaction, impairment of vascularity, and possible obstruction to successful sprouting. In addition, there are occasions when it is virtually impossible to perform a suture repair because of limited exposure and/or very fine structures, such as are encountered in pediatric cases. These situations have continued to provide the impetus for evaluating alternative methods of nerve coaptation. Recently, the use of tissue glue has gained in popularity as a technique for sutureless nerve repairs. We decided to test the efficacy of fibrin glue repair versus microsuture coaptation in the rat sciatic model. The repair sites were assessed for tensile strength, by quantitative morphometry, and by electrophysiologic studies. Tensile strength findings revealed that at two, four, and eight weeks after surgery, there was no significant difference between the two repair techniques, although there was a trend toward a stronger hold in the microsuture repairs. Electrophysiologic recordings revealed that conventional microsuture repairs had significantly faster conduction velocities, larger area under the curve, and higher peak amplitudes. The onset and peak latencies were comparable, revealing that the axonal quality of at least a certain number of axons was similar electrically. Axonal counts both proximal and distal to the repair showed no significant difference, although there was an overall suggestion of superiority in the number of myelinated axons in the suture repair. PMID- 2269956 TI - Frequent use of the term "vascularized bone graft". PMID- 2269955 TI - Pretransfer tissue expansion of a scalp free flap for burn alopecia reconstruction in a child: a case report. AB - A nine-year-old boy who sustained severe grease-fire burns over his right scalp, face, neck, and trunk 14 months previously, presented with extensive alopecia over the right frontotemporoparietal scalp. Near complete coverage of the scalp defect was obtained with pretransfer expansion of the left temporoparietal scalp, followed by free-flap transfer of the expanded tissue to the defect. Pretransfer tissue expansion has the advantages of increasing flap surface area and minimizing donor site deformity. This case illustrates the applicability of pretransfer tissue expansion of free flaps, and demonstrates the excellent results achievable with free-flap scalp transfers. PMID- 2269957 TI - Homo sapiens--a species too successful. PMID- 2269958 TI - The health of women at work. PMID- 2269959 TI - Bone scan appearances after uncemented hip replacement. AB - Persistent increased uptake on a technetium bone scan after a cemented hip replacement usually indicates pathology, either loosening or infection. The natural history of scan appearances in uncemented replacements is different and can be predicted from a plain X-ray. The diagnostic value of a bone scan is therefore questionable when investigating pain after uncemented hip replacement. PMID- 2269960 TI - General practitioner referrals to an eye hospital: a standard referral form. AB - To assess general practitioner (GP) referrals to an eye hospital, 500 consecutive referral letters were analysed for content, diagnosis, ocular examination, and medical and drug history. Inadequate information was provided. Visual acuity was measured by general practitioners in only 3.7% of referrals. The standard of ocular examination compared unfavourably with that of ophthalmic opticians. A standard ophthalmic referral form is proposed, and referral protocols are desirable. Undergraduate education in ophthalmology is inadequate and requires more curricular time. PMID- 2269961 TI - Gastrointestinal complications of the haemolytic uraemic syndrome. AB - The haemolytic uraemic syndrome (HUS) is a well recognized cause of acute renal failure in children. Gastrointestinal involvement is common, and may result in rectal bleeding which can be an important presenting symptom. Previous publications have stressed the importance of correct diagnosis to avoid unnecessary surgery. Occasionally serious gastrointestinal complications do occur. We present five children with life-threatening gastrointestinal complications of the HUS and discuss the indications for laparotomy. PMID- 2269962 TI - Eosinophilic cystitis mimicking invasive bladder tumour: discussion paper. PMID- 2269963 TI - Role of vitrectomy in the management of retinal detachments. PMID- 2269964 TI - On the possible role of viruses in the aetiology of motor neurone disease: a review. PMID- 2269965 TI - Gentlemen of the hammer: British medical geologists in the 19th century. PMID- 2269967 TI - Acute hyperventilation in literature: notes on four examples. PMID- 2269968 TI - Metastatic accessory breast carcinoma in a thoracic subcutaneous nodule. PMID- 2269969 TI - Ehlers-Danlos syndrome with recurrent bruising. PMID- 2269966 TI - Requirements for medical research-perceptions from Joseph Lister's development of chromic catgut. PMID- 2269970 TI - Atypical X-linked variant of chronic granulomatous disease. PMID- 2269971 TI - Surgical treatment for Crohn's disease of the fourth part of the duodenum. PMID- 2269972 TI - Fatty liver with malignant CT features. PMID- 2269973 TI - A rare complication of endotracheal intubation. PMID- 2269974 TI - Abdominal lymphomas. PMID- 2269975 TI - The Zed expedition. PMID- 2269977 TI - Holistic medicine. PMID- 2269976 TI - Drug-induced epistaxis? PMID- 2269978 TI - From Da Vinci to Harvey. PMID- 2269979 TI - Chronic snorers and sleep apnea. PMID- 2269980 TI - The death of Schubert. PMID- 2269982 TI - Atlantoaxial instability. PMID- 2269981 TI - Spontaneous rupture of renal artery aneurysm. PMID- 2269983 TI - Human companion-animal relationships in the veterinary consulting room. AB - A questionnaire, based on 14 years' private practice experience and psychological principles, was compiled to establish the reasons why veterinary clients are involved with their pets. Questionnaires were sent to South African veterinarians country-wide and only clients visiting veterinarians were requested to complete the questionnaires anonymously. Questionnaires (n = 612) were returned and the data was processed by computer. The results indicated that clients are involved with their companion animals for emotional, social and relaxational reasons, which all have psychological implications. They are, however, also involved with their animals by caring for them, and they keep them for utility or economical reasons and also due to their general interest in nature. The latter reasons could be seen as natural reasons for keeping pets. The same relationship between clients and their pets continue during veterinary consultations. Because of this continuing involvement, some clients may consult veterinarians mainly for psychological reasons and others mainly for clinical reasons. There is a constant interaction between these motivations for veterinary consultations. Client consultations of veterinarians could thus be categorised into psychological consultations which are predominantly human/client orientated and clinical consultations which are predominantly animal/patient orientated. PMID- 2269984 TI - Arterial blood supply to the ileocaecal junction in the horse. AB - The arteries supplying the ileocaecal junctions of 7 horses were injected with latex via the A. ileocolica and dissected macroscopically. The same basic pattern emerged whereby a single papillary artery arising from the R. ilei mesenterialis, supplied all aspects of the ileocaecal papilla. In one instance, the papillary artery arose directly from the ileocolic artery. No collateral arterial supply to the ileocaecal junction was present in any of the specimens dissected. PMID- 2269985 TI - Treatment of cerebral coenuriosis in sheep with praziquantel. AB - Sheep (n = 14) with coenuriosis were treated with praziquantel in single or divided doses at total dosage rates of 50 to 500 mg kg-1 live mass. Nine of the sheep also received corticosteroid, diuretic and analgesic supportive therapy. Stress was avoided as far as practically possible. Treatment of one sheep with acute coenuriosis at a total dosage rate of 500 mg kg-1 praziquantel, was unsuccessful. Eight sheep were successfully treated at total dosages ranging from 100 to 500 mg kg-1 live mass, whereas dosages of 50 mg kg-1 were successful in 2 sheep only. Dosages of 50 mg kg-1 in 2 other sheep with multiple cerebral coenuri, were unsuccessful or only partially successful in killing parasites. PMID- 2269986 TI - Parasites of cattle in the south western Orange Free State. AB - A number of young Friesian oxen were slaughtered (one at a time) for parasite recovery for 12 consecutive months, from April 1987 to March 1988, on a farm in the Fauresmith district of the south western Orange Free State. A total of 5 ixodid and one argasid tick species, 2 lice species, plus one nematode species and one cestode species, were recovered. Peak numbers of adult Hyalomma marginatum rufipes were present from November 1987 to February 1988, while the largest numbers of Hyalomma truncatum were recovered during September 1987 and from November 1987 to January 1988. Adult Ixodes rubicundus were recovered only during April and June 1987. Adult ticks of a Rhipicephalus sp. near R. punctatus were present during April and from September to November 1987 and in January 1988. No pattern of seasonal abundance was evident for the other tick species, the lice or the helminths. PMID- 2269987 TI - Amoebic meningoencephalitis in a sheep. AB - A case of amoebic meningoencephalitis in a sheep, suspected of being caused by Acanthamoeba sp., is described. An adult ewe was necropsied 5 days after it had developed anorexia and nervous signs, which included ataxia and walking in circles. Significant gross lesions were restricted to the central nervous system and consisted of thickening of the meninges and extensive necrosis of the cerebrum and cerebellum. The cerebral changes were characterised microscopically by a multifocal to coalescent necrotising granulomatous meningoencephalitis as well as choroid plexitis, ventriculitis and diffuse vasculitis. Numerous amoebic trophozoites and a few encysted forms morphologically compatible with Acanthamoeba sp. were present in the affected areas, particularly in the walls of blood vessels and perivascular spaces. PMID- 2269988 TI - Accidental pentobarbital poisoning in a lioness. AB - A lioness was accidentally poisoned by consumption of meat of a horse euthanased with pentobarbital. The post mortem examination was negative but thin-layer gas chromatographic and mass-spectrometric methods revealed a pentobarbitone concentration of 1, 14 mg kg-1 in the chloroform extracts of the liver of the animal. PMID- 2269989 TI - An outbreak of suspected Phalaris staggers in sheep in the western Cape Province. AB - An outbreak of suspected Phalaris staggers in South Africa is described. Approximately 40 out of 600 sheep that had been grazing for 3 weeks on a wheat stubble land heavily infested with Phalaris grass, were affected. Clinical signs included nervous tremors, ataxia and convulsions. New cases occurred even after removal from the affected pasture. The most prominent microscopic lesion seen in the 2 sheep autopsied, was an accumulation of intracytoplasmic brown pigment in the neurons of the brain. PMID- 2269990 TI - An outbreak of granulomatous vulvitis in feedlot heifers. AB - An unusual form of vulvitis occurred in outbreak form affecting at least 18 of a group of 35 to 40 heifers soon after their introduction to a feedlot in the western Transvaal area of the Republic of South Africa. Initially, affected animals showed a knob-like swelling of the ventral commissure of the vulva. This grew in size up to approximately 6 cm in diameter and then appeared to burst open and give rise to a granulomatous lesion. Bovine herpesvirus type-1, Moraxella bovis, Mycoplasma bovigenitalium and Mycoplasma bovis were isolated from 2 affected heifers referred for diagnostic investigation. Mycoplasma canadense was isolated from one of the heifers. Attempts to reproduce the disease by transferring an excised portion of the lesion to unaffected animals, resulted only in lesions typical of uncomplicated infectious pustular vulvovaginitis. It is proposed that that multifactorial aetiology, including synergistic pathogenic action between the organisms isolated, was responsible for this outbreak. Administration of oxytetracycline to affected animals was followed by prompt resolution of symptoms. No further outbreaks have been reported. PMID- 2269991 TI - Interactions of dietary cation-anion balance and phosphorus: effects on blood, bone and faecal phosphorus concentration in dairy calves. AB - Dietary levels of cations and anions are shown to have an effect on concentrations of phosphorus (P) in blood, bone and faeces of dairy calves between 9 and 19 weeks of age. Calves fed diets high in anions, demonstrated higher concentrations of P in blood and faeces than calves whose diets were high in cations, and at the same time demonstrated lower concentrations of P in bone. Compared to diets with high cation levels, diets high in anions produced significantly (p less than 0.05) higher concentrations of total P in the faeces at different stages in the experiment, higher serum inorganic phosphorus (SiP) concentrations and lower P concentrations in the bone, which were significant at the end of the trial (P less than 0.06). When the diet was low in P (0.22%), the cation-anion balance of the diet seemed to have the greatest effect, so that the interaction of dietary P and dietary cation-anion balance (DCAB) was responsible for changes in blood, bone and faeces. PMID- 2269992 TI - DNA screening for hereditary goitre in Afrikander cattle. AB - DNA isolated from blood samples of Afrikander cattle (n = 66) were screened by blot-hybridisation analysis to determine the frequency of carriers of the goitre mutation. No carriers were found, suggesting that the frequency of the goitre mutation is less than 0.01. PMID- 2269993 TI - The chemically dependent woman. PMID- 2269995 TI - Thoughts on quality, access, and expenditures. PMID- 2269994 TI - Percutaneous endovascular therapy for inoperable intracranial aneurysms. PMID- 2269996 TI - Medicine and money in Mississippi. PMID- 2269997 TI - Organic dust toxic syndrome: an acute febrile reaction to organic dust exposure distinct from hypersensitivity pneumonitis. AB - Organic dust toxic syndrome is a term recently coined to describe a noninfectious, febrile illness associated with chills, malaise, myalgia, a dry cough, dyspnea, headache and nausea which occurs after heavy organic dust exposure. Organic dust toxic syndrome shares many clinical features with acute farmer's lung and other forms of hypersensitivity pneumonitis, including the presence of increased numbers of neutrophils in bronchoalveolar lavage. However, organic dust toxic syndrome differs from acute hypersensitivity pneumonitis in several respects: the chest X-ray does not show infiltrates, severe hypoxemia does not occur, prior sensitization to antigens in the organic dust is not required and there are no known sequelae of physiological significance, such as the recurrent attacks and the pulmonary fibrosis which may be seen with chronic hypersensitivity pneumonitis. Organic dust toxic syndrome is thought to be much more common than farmer's lung. It is important for clinical and investigational purposes that organic dust toxic syndrome be distinguished from acute farmer's lung. PMID- 2269998 TI - Assessment of efficacy of activated charcoal for treatment of acute T-2 toxin poisoning. AB - "Superactive" charcoal was assessed for efficacy in decreasing the lethality of both oral and parenteral exposure to T-2 toxin, a fungal metabolite which can cause death or illness upon ingestion. In vitro binding studies, analyzed using the Langmuir adsorption isotherm, showed that activated charcoal had a maximal binding capacity of 0.48 mg toxin/mg charcoal and a dissociation constant of 0.078 mg charcoal/l. In vivo, orally administered, activated charcoal was assessed for treatment of acute oral or parenteral exposure to T-2 toxin in mice. Following oral toxin administration (5 mg/kg), untreated mice showed only 6% survival after 72 hr. Charcoal treatment (7 g/kg,po) either immediately or 1 hr after toxin exposure resulted in significant improvement in survival with values of 100% and 75%, respectively. Following parenteral toxin exposure (2.8 mg/kg, sc), untreated and charcoal-treated (7 g/kg, po) mice showed 50% and 90% survival, respectively, after 72 hr. LD50 value for T-2 toxin, determined at 96 hr after intoxication, increased significantly from 2 mg/kg for untreated controls to 4.5 mg/kg for activated charcoal treatment. PMID- 2269999 TI - Carbamazepine overdose: a prospective study of serum levels and toxicity. AB - A cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age, chronic exposure, or previous disorder or cardiovascular disease could be used as prognostic indicators. Seventy-three consecutive cases were collected from two regional certified poison control centers from January 1989 to August 1989. There were 25 exposures in children less than 6 yrs., 11 exposures in adolescents, and 37 exposures in adults. Ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information. Peak measured serum levels ranged from 0.3 to 56 mcg/ml. Using the presence of coma, seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity, we found poor correlation between rising serum levels of carbamazepine and toxicity. Increased serum levels of carbamazepine did appear to correlate with increased hospital stay, but not with ICU stay. History of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose. In this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect. Serum levels below 40 mcg/ml do not appear to accurately predict the severity of toxicity. Cardiac conduction defects were rare (one child). Anticholinergic findings, as evidence by decreased bowel motility and sinus tachycardia were common. Previous cardiovascular disease and age did not appear to be important prognostic indicators. PMID- 2270000 TI - Pulmonary pathology in severe malaria infection in health and protein deprivation. AB - Histopathological changes in the lung resulting from infection with a virulent strain of the malarial parasite, Plasmodium knowlesi, in healthy and protein deprived Rhesus monkeys were studied. Pertinent changes noted were a high degree of parasitized red cells in septal capillaries, microinfarcts, alveolar and interstitial oedema, interstitial pneumonitis, bronchopneumonia, and injury to septal capillary wall which may be secondary to the production of tumour necrosis factor. These changes were more marked in the non-protein-deprived monkeys. PMID- 2270001 TI - Determinants of domestic water use in rural Nicaragua. AB - In order to investigate the factors affecting domestic water use in rural areas of developing countries, an analysis was performed of water consumption estimates from 1029 different households in Nicaragua collected between May 1986 and December 1988. Eight of the 22 variables hypothesized to be related to per capita domestic water consumption, were included in the final multiple regression model. These were; household size, site of clothes washing, the type of water source, mother's and father's levels of schooling, distance to the water source, wealth, and ownership of cattle. According to this model, a decrease in the distance to the water source from 1000 to 10 m is associated with an increase in per capita water consumption of 20%. Similarly, families where the mother has 6 years of schooling use 17% more water than families where the mother has had no formal education. The same difference in the father's schooling is associated with 12% greater per capita water consumption. A better understanding of the factors affecting domestic water use is needed to improve the design of interventions aimed at reducing the transmission of water-washed disease in developing countries. PMID- 2270002 TI - Comparison of thick blood smear and saponin haemolysis for the detection of Loa loa and Mansonella perstans infections. AB - In an endemic area, Loa loa and Mansonella perstans microfilariae were detected by the examination of 5 ml blood in respectively 7.4 and 26.2% of subjects who would have been erroneously considered amicrofilaraemic by the conventional method of two thick blood smears (40 microliters blood). Correction factors to be applied to the results obtained with thick blood films in order to approach the true parasitological prevalences were 1.5 for L. loa and 1.6 for M. perstans. In addition, the analysis of a large volume of blood provides a better estimation of microfilarial load of the parasitized population. PMID- 2270003 TI - Plasma chloroquine measurement in the evaluation of Plasmodium falciparum sensitivity. AB - In-vivo assessment of the sensitivity of Plasmodium falciparum to chloroquine was carried out in 63 patients in eastern Sudan. Standard triple-dose therapy with chloroquine (25 mg base kg-1 body wt) failed in curing 30 patients. All grades of resistance were demonstrated in the study, confirming that the phenomenon of chloroquine resistance is well established in this area. Factors which may have accelerated the spread of resistant strains include: a drop in the immunity of the local people caused by previous drought, introduction of non-immune refugees, increased transmission following heavy rains, and massive drug pressure. Plasma levels of chloroquine attained in our patients exceeded the therapeutic level and thus ruled out ineffective levels as a possible cause of treatment failure. Moreover, there was no significant difference between chloroquine levels in patients infected with sensitive or resistant strains. As some patients were cured with an additional dose of chloroquine, it is proposed that chloroquine measurement be carried out in patients treated for falciparum malaria with a view to defining new effective levels for semi-immune populations. PMID- 2270005 TI - Tumoral calcinosis: a study of cases from Papua New Guinea. AB - Forty-eight cases of tumoral calcinosis were recorded in surgical pathology material, Port Moresby General Hospital, Papua New Guinea during the period from 1981 to 1985. The lesions were most common in the fifth decade of life and the female to male ratio was 2:1. The hip region and the greater trochanter were the common sites involved and this observation supports the possible aetiological relationship of tumoral calcinosis to trauma resulting in pressure ischaemia. In this series, from a country in which the condition is well known, only 35.8% were correctly diagnosed preoperatively. With a knowledge of its clinicopathological features, it should be possible for most cases to be diagnosed preoperatively. PMID- 2270004 TI - Risk factors for malaria among British missionaries living in tropical countries. AB - Thirty-two episodes of malaria (10 confirmed by laboratory tests) were reported by 162 people living in 18 developing countries under the auspices of one British missionary society. Malaria was endemic in all countries involved, and a total of 367 person-years were observed. The overall incidence rate for malaria was 87.3 per 1000 person-years at risk. Important factors identified were residence in West Africa compared with elsewhere (relative risk (RR) = 13.0, P less than 0.001), being in the 20-39 year age group (RR = 3.2, P less than 0.002), history of gastroenteritis (RR = 3.1, P less than 0.002) and living in a rural area (RR = 1.7, n.s.). Chemoprophylaxis was taken by 119 people (73.5%). PMID- 2270006 TI - Survey of enteropathogenic agents in children with and without diarrhoea in Ghana. AB - A survey was carried out over 1 year in a rural area of Ghana on the isolation, detection and/or identification of enteric pathogens from children under 5 years of age with and without diarrhoea. The isolation and detection rate of Shigella flexneri, Shigella dysenteriae, Giardia lamblia and Rotavirus were higher in children with diarrhoea than in controls. Yersinia enterocolitica, Vibrio cholerae and Vibrio parahaemolyticus were not isolated during the period of this survey. The incidence of other enteropathogenic bacteria and parasites identified in the diarrhoeal and non-diarrhoeal children was calculated and is discussed in this study. PMID- 2270007 TI - Persistent occurrence of beta-haemolytic streptococci in a population of Lagos school children. AB - A total of 354 (8%) out of 4395 primary school pupils located in seven Lagos primary schools were positive for beta-haemolytic streptococci (BHS). Eighty three (23%), 99 (28%) and 113 (32%) of the respiratory tract isolates and 25 (53%), 14 (30%) and seven (15%) of the skin-lesion isolates were identified as belonging to Lancefield groups A, C and G respectively. Prevalence rate of BHS in a rural school was different from that in urban schools. PMID- 2270008 TI - A survey of tinea capitis in primary school children in Harare, Zimbabwe. AB - A survey of the prevalence and appearance of tinea infections and associated dermatophytes in schools in Harare is reported. Of 704 children examined, 29% showed clinical evidence of tinea capitis; of these, 86% had mycological evidence of infection. Dermatophytes were isolated from 69% of all the specimens. The most common was Trichophyton violaceum (78% of the isolates), 9% of the dermatophytes were Microsporum audouinii, and other isolates were T. mentagrophytes, T. yaoundei, M. gypseum and M. canis. PMID- 2270009 TI - Urine methylhistamine concentrations before and after chloroquine in healthy black subjects. AB - Urine concentrations of methylhistamine were measured in 11 subjects who experienced itching with chloroquine ('itchers') and in 14 who did not itch ('non itchers'). In each group, urine methylhistamine concentrations were significantly greater at 12, 24 and 36 h after ingestion of 1 g chloroquine phosphate than before. There was no significant difference between itchers and non-itchers as regards urine methylhistamine concentrations at any time-point. Furthermore, there was no correlation between urine methylhistamine concentration and degree of pruritus in itchers. The findings suggest that histamine may be released by chloroquine, but it is unlikely to be the main cause of chloroquine-induced pruritus. PMID- 2270010 TI - [Plasma lipoproteins: structure and function]. PMID- 2270011 TI - [Metabolic pathway of lipoproteins]. PMID- 2270012 TI - [The enzymes related to lipoprotein metabolism (LpL, H-TGL, LCAT, ACAT, HMG-CoA reductase, 7 alpha-hydroxylase)]. PMID- 2270013 TI - [Cholesterol ester transfer protein (CETP)]. PMID- 2270015 TI - [Modified LDL and its physiological significance]. PMID- 2270014 TI - [Interaction of HDL with cells]. PMID- 2270016 TI - [Chylomicronemia]. PMID- 2270017 TI - [Primary hypercholesterolemia]. PMID- 2270018 TI - [Endogenous (type IV) hypertriglyceridemia]. PMID- 2270019 TI - [Type III hyperlipidemia]. PMID- 2270020 TI - [Primary hyper-high density lipoprotein-cholesterolemia]. PMID- 2270021 TI - [Secondary hyperlipidemia due to diabetes mellitus ]. PMID- 2270023 TI - [Hyperlipidemia in obesity]. PMID- 2270022 TI - [Secondary hyperlipidemia due to endocrine disorders]. PMID- 2270024 TI - [Hyperlipidemia in renal diseases]. PMID- 2270025 TI - [Liver diseases and hyperlipidemia]. PMID- 2270026 TI - [Hematological disorder and hyperlipoproteinemia]. PMID- 2270027 TI - [Alcohol or drug induced hyperlipidemia]. PMID- 2270028 TI - [Diet therapy of hyperlipidemia]. PMID- 2270029 TI - [Physical fitness in the treatment of hyperlipidemia]. PMID- 2270030 TI - [Drug therapy of hyperlipidemia]. PMID- 2270031 TI - [LDL-apheresis therapy of hyperlipidemia]. PMID- 2270032 TI - [Hyperlipidemia in childhood]. PMID- 2270033 TI - [Hyperlipidemia in elderly]. PMID- 2270034 TI - [The role of hyperlipidemia in the development of atherosclerosis]. PMID- 2270035 TI - [LCAT deficiency]. PMID- 2270036 TI - [Disorders of lipoproteins and lipid peroxides]. PMID- 2270037 TI - [Advance in determination method of lipid]. PMID- 2270038 TI - [Detection of HTLV-I gene expression by using the polymerase chain reaction]. PMID- 2270039 TI - The Japanese Journal of Physiology. Proceedings of the 67th annual meeting. April 3-5, 1990 (Miyazak). PMID- 2270040 TI - Development and characterization of the IOR/Hab inbred mouse strain. AB - The IOR/Hab inbred mouse strain, developed and maintained in the National Institute of Oncology and Radiobiology, is the first inbred strain to be developed in Cuba. It has a high fertility in this tropical climate. A number of physiological characteristics such as longevity, haematological characteristics, and growth are reported. Other experiments and results concerning spontaneous tumour frequency suggest that the strain is well adapted to standard environmental conditions, and could be useful for biomedical research. PMID- 2270041 TI - The mouse epidermis as a model in skin pharmacology: influence of age and sex on epidermal metabolic reactions and their circadian rhythms. AB - The influence of age and sex on epidermal metabolism and histology was studied in mice (NMRI). Within a few weeks postpartum, thymidine triphosphate incorporation into DNA and amino acid incorporation into epidermal protein decreased. Differences between tail epidermis and other skin regions (back, abdomen, ear) were found. Sex dependent differences could not be demonstrated. A circadian rhythm of the studied epidermal metabolic processes was shown (artificial 12L:12D light/dark cycle). Maximum incorporation of thymidine triphosphate and of amino acids was found at the end of the light period at 1800 h, while a minimum incorporation was demonstrated at the end of the dark period. Considering described biological variations, the mouse tail assay seems to be suited to study influences of drugs in epidermal metabolism and histology. PMID- 2270042 TI - An apparatus for the measurement of lung volume and compliance in mice. AB - Pressure-volume (P-V) curves and total lung capacity (TLC) were measured in excised lung of mice using a water manometer and a closed system in which the humidity and temperature were controlled. In pathogen-free mice there are no significant differences in elastic properties of these lungs in relation to their age. The measured TLC in those normal mice was approximately 2.9 ml. This relatively simple apparatus which allows one to make sensitive and accurate measurements of pulmonary function in mice and other small animals. PMID- 2270043 TI - Background pathology in BDF1 mice allowed to live out their life-span. AB - Fifty male and 50 female BDF1 mice were observed allowing them to live out their life-span. Mortality up to 104 weeks of age was higher in males (42%) than in females (34%), and the 50% survival age was 112 weeks for males and 118 weeks for females. Body weight reached the peak at 82 weeks of age in males and 92 weeks of age in females, showing the mean body weight of 54.3 g for males and 48.0 g for females. The incidence of calculi and proteinaceous casts in the kidneys, that were not associated with exposure to chloroform, cell-alteration in the adrenal cortex, and islet cell hyperplasia in the pancreas was significantly higher in males than in females. On the other hand, hyaline droplet degeneration of the renal tubular epithelium, spindle cell proliferation in the adrenal cortex and milk-retention in the mammary glands occurred at a significantly higher incidence in females than in males. Cerebral mineralization in both sexes, atrophy and calcification of the testes and enlargement of the seminal vesicles of males, as well as cyst-formations in the ovary and endometrium of females developed at a very high incidence. Frequent neoplasms in males were hepatocellular adenomas and carcinomas, blood vessel tumours, pulmonary adenomas and carcinomas, and malignant lymphomas. In females, malignant lymphomas were the most common neoplasm, followed by blood vessel tumours, chromophobe pituitary adenomas and hepatocellular adenomas. Hepatocellular carcinomas developed only in males, whereas the histiocytic and lymphocytic types of malignant lymphomas and chromophobe cell adenomas arose solely or at a significantly higher incidence in females than in males. PMID- 2270044 TI - In vivo activity of orally administered antibiotics and chemotherapeutics against acute septicaemic pasteurellosis in rabbits. AB - Different antibiotics and chemotherapeutics were tested for therapeutic efficacy in rabbits, in an experimental model using a Pasteurella multocida strain which causes hyperacute septicaemia in this animal species. Only enrofloxacin, administered in the drinking water at a concentration of 50-100 mg/l cured the rabbits, provided that a daily intake of 5 mg/kg body weight was achieved. The other drugs tested (tetracycline, spiramycin, erythromycin and a combination of sulfamerazine with trimethoprim), at doses recommended for rabbits, showed little or no activity at all, with the exception of chloramphenicol, which was only partially effective. PMID- 2270045 TI - Sex ratio and litter size in relation to parity and mode of conception in three inbred strains of mice. AB - Breeding records from three inbred strains of mice (BALB/c ABom, C57BL/10ScSn, C3H/He/Kon) were examined with respect to the effects of parity and mode of conception upon litter size and sex ratio at birth. Litters from 3 modes of conception were considered: litters of primipares, litters of multipares conceived during postpartum oestrus and litters conceived after lactational anoestrus. Litters of multipares were assigned to one of these latter groups according to the inter-litter intervals. Parity had no significant effect upon the sex ratio but had a significant one upon the litter size, which did not vary between the strains when first litters were excluded from analysis. The expected variations in response to the mode of conception were found in BALB/c ABom mice but both the effects on the litter size as well as on the sex ratio varied significantly between the strains. Litter size reduction per se could be ruled out to be the cause of the sex ratio variations found. Rather, it is suggested that sex-specificity of embryonic loss depends upon the mode of conception. PMID- 2270046 TI - Gnotobiotic, athymic mice; a possible system for the study of the role of bacteria in human amoebiasis. AB - Two groups of 12 + 14 gnotobiotic, athymic mice were intracaecally injected with Entamoeba histolytica strain HK9 and NIH:200, respectively. Two groups of 16 and 15 mice were given amoebae together with a pure strain of Escherichia coli and a further two groups of 16 and 27 were given amoebae with a pure strain of Clostridium perfringens. Batches of 3-7 mice from each group were killed at intervals of 1-4 weeks. All the mice given NIH:200 alone were found to be infected with trophozoites. Of those given HK9 alone, 20% of the first and 57% of the second group to be examined were infected. Groups of mice given either strain of amoeba monocontaminated with E. coli were all found to be infected at post mortem examination with no apparent clinical signs and little histological change. The group given HK9 and C. perfringens, although all were infected, failed to produce clinical signs or histological lesions, though some died expectedly. In the group given NIH:200 with C. perfringens the amoebae showed a change of activity and there was evidence of both caecal and liver lesions after 120 days. The usefulness of the system in studying the effect of individual species of bacteria on invasive amoebae is discussed. PMID- 2270047 TI - Allergy to laboratory mice and rats: a review of the pathophysiology, epidemiology and clinical aspects. AB - Allergy to laboratory animals (mice and rats) is reviewed. Immunological aspects, the relevant allergens, epidemiology, clinical manifestations, diagnosis and prognosis are discussed. Results presented in some studies are analysed and criticized. PMID- 2270048 TI - Outcome of acute subdural and epidural hematomas in a level I trauma center in South Carolina. PMID- 2270050 TI - Will a new study of health care costs make a difference? An analysis of the report of the Blue Ribbon Task Force to Study Health Care Costs in South Carolina. PMID- 2270049 TI - A modified cystourethropexy in the management of incontinence and dyspareunia. PMID- 2270052 TI - Medicine's greatest problem. PMID- 2270051 TI - Continuous quality improvement (CQI): solution to QA shortcomings? AB - In the previous decade, quality assurance gained prominence in an effort to ensure optimal medical care. Some experts, as Avedis Donabedian, M.D.--a leading scholar in the area of quality assessment--characterized its dimensions as falling into three categories: structure (inputs), process and outcome. Paul Ellwood, M.D., in 1988, further promoted the latter by introducing an "outcomes management" system. Now Berwick, James, O'Leary and others advocate the incorporation of certain industrial insights advocated by Deming, Juran and others to improve traditional QA Methods and develop a process of Continuous Quality Improvement (CQI). The goal is to have patients (and other customers) better served. PMID- 2270053 TI - An essay on inoculation: Dr. James Killpatrick. PMID- 2270054 TI - Independent threats and self-evaluation maintenance processes. AB - The present study investigated the independence of Self-Evaluation Maintenance (SEM) processes and the larger self-system. SEM processes are activated whenever another's performance is made salient relative to one's own. According to the SEM model, when one is outperformed by a close other on a task high in self relevance, self-esteem is lowered and a negative affect state is generated. When one is outperformed by a close other on a task low in self-relevance, however, self-esteem and positive affect are actually enhanced, because one can take pride in the other's accomplishments. There are many sources of threat or enhancement to self-esteem, however, that are unrelated to one's performance relative to another's. The present study, using American undergraduates as subjects, examined the impact that these unrelated self-esteem threats or enhancements might have on SEM processes, that is, whether a prior unrelated ego-threatening or ego enhancing experience modulates the effects of SEM processes. It was expected that a prior ego-threatening experience would augment the impact of SEM variables, whereas an ego-enhancing experience would attenuate the effect. Results, however, indicated little interaction between SEM processes and unrelated threats or enhancements to self-esteem. PMID- 2270055 TI - Correlates of attitudes toward AIDS. PMID- 2270056 TI - Multiple alcohol-related problems in the United States: on the rise? AB - Are drinking problems on the rise in the U.S. general population? Surveys of drinking practices and problems conducted in the United States in 1967, 1969, 1979 and 1984 included numerous questions on alcohol-related problems that were identical or nearly identical in wording. Using data from these surveys, we tested for ordered increases over time in the prevalence of an indicator of multiple problems, considered on both a current (1-year) and lifetime basis. We studied prevalence in men and women between the ages of 22 and 59 in all four surveys. Prevalence of the multiple problem indicator was rare, especially when considered on a current basis. However, relative increases in prevalence ranging from 53% to over 200% were found from 1967 to 1984 in the multiple problem indicator for men and women, for lifetime as well as current problems. With the exception of current problems in women (a very rare condition even in the 1984 survey), these changes were all statistically significant or showed a trend toward significance. When respondents were subgrouped by age, all subgroups still showed increases since 1967, although sample sizes decreased and significance tests of ordered increases over time were not so consistent. PMID- 2270057 TI - Alcohol-predictive cues enhance tolerance to and precipitate "craving" for alcohol in social drinkers. AB - This study attempts to show that tolerance to alcohol is in large part a "learned" response, precipitated by contextual cues predictive of the unconditional drug effect. It also aims to show that the contextual cues integral to such "environment-dependent" tolerance function to increase motivational desire to drink alcohol. Male students (N = 40), drinking on average 10-20 units of alcohol per week, were randomly assigned to one of four groups. Two groups ingested 1.2ml/kg alcohol: one (AL-EXPT) with exteroceptive contextual cues typically associated with alcohol use, and the other (AL-UNEXPT) in a context not normally associated with alcohol. A third group (placebo) believed that they were drinking alcohol but, in fact, consumed a nonalcoholic beverage in the alcohol expected context. The fourth group drank juice in the alcohol-unexpected context. As predicted, tolerance to the deleterious effects of alcohol on cognition and motor-performance, and subjective desire to consume alcohol, were influenced by the alcohol-predictive contextual cues. A physiological index (pulse rate) also tended to confirm that these cues elicited a conditioned compensatory response to alcohol. The implications of these findings for tolerance to and motivation to drink alcohol in a nonpathological population are discussed. PMID- 2270058 TI - Some boundary conditions for effective use of alcohol placebos. AB - The present research assessed the conditions under which subjects who consume alcohol and those who consume a placebo beverage, and who report consuming alcohol on a manipulation check question, are equivalent with respect to subjective responses to alcohol. Male subjects were told that they were drinking alcohol and consumed one of four beverages: alcoholic beer, nonalcoholic beer, vodka and tonic with lime, or tonic with lime. Measures of subjective intoxication, body sensations and breath alcohol were taken at different times during and after beverage consumption. Subjective intoxication ratings were higher for subjects who received alcohol, compared to subjects who received a placebo and reported consuming alcohol, when alcohol subjects achieved blood alcohol concentrations at and above .04%. These two groups did not differ in subjective intoxication ratings when alcohol subjects achieved blood alcohol concentrations below .04%. These data suggest that the orthogonal manipulation of alcohol consumption and expectancy effects is problematic at and above blood alcohol concentrations of .04%. PMID- 2270059 TI - Diagnostic validity of the MAST and the alcohol dependence scale in the assessment of DSM-III alcohol disorders. AB - The comparative validity of the Michigan Alcoholism Screening Test (MAST) and the Alcohol Dependence Scale (ADS) in screening for current DSM-III alcohol abuse/dependence disorders is evaluated. These scales were administered to 501 patients presenting for treatment of alcohol or drug problems. DSM-III alcohol disorders are diagnosed using the Diagnostic Interview Schedule. Receiver Operating Characteristic (ROC) analysis is used to determine optimum threshold scores for the MAST and ADS and to compare the screening ability of the two instruments. Optimum cut points for the MAST and the ADS are 12/13 and 8/9, respectively. The overall accuracy of classification for both instruments using these threshold scores is 88%. The areas under the ROC curves are .91 and .90 (SD = .02) and there are no significant differences between the MAST and the ADS in their ability to screen for alcohol abuse or dependence in this population. The MAST and the ADS correlate highly with each other (.79). The results reported in our study should be applicable to the revised DSM-III since a field trial found a high level of agreement on alcohol disorders between the diagnostic systems. Categorical versus dimensional approaches to the assessment of alcoholism are discussed. PMID- 2270060 TI - Prediction of adults' drinking patterns from the drinking of their parents. AB - While studies have shown relationships between adolescent and parental drinking patterns, it is not known if these parental influences are maintained when the children are adults and further removed from early influences. A representative general population sample of 6,364 adults living in New York State were interviewed regarding their current drinking as well as about their family structure and the drinking patterns of their parents while they were growing up. A logit modeling analysis revealed that natural father's drinking while growing up, natural mother's drinking while growing up, family structure (father present or not) and sex of the respondent were all significant predictors of current heavy drinking of adults even while controlling for all of the other variables in the model. It is concluded that early family influences may have long-term consequences on drinking behaviors. PMID- 2270061 TI - Elderly men with histories of heavy drinking: correlates and consequences. AB - Recognition that the physical, psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly. We examined the characteristics of elderly men with self-reported histories of having ever been heavy drinker (H+) in a population-based (N = 1,155, mean age = 73.7 years) longitudinal survey of community-dwelling elders; 10.4% of the men reported that they had been heavy drinkers at some time during their lives. H+ men were younger and less educated than non-heavy drinkers (H-) or never drinkers (N). Mortality was higher among H+ men who were current drinkers than among H- or N men. H+ men reported more major illnesses, poorer self-perceived health status, more physician visits, more depressive symptoms, lower levels of life satisfaction and smaller social networks than did H- or N men. Self-reported ability to perform activities of daily living and instrumental activities of daily living was poorest among H+ men, who also scored the lowest on a mental status examination. Thus, a history of having ever been a heavy drinker is predictive of widespread impairments in physical, psychological and social health and functioning among elderly men. PMID- 2270062 TI - Drinking in college: consumption patterns, problems, sex differences and legal drinking age. AB - Data from 606 (75.8%) undergraduate respondents drawn from a random sample (N = 800) at Rutgers University demonstrate that, although fewer college students may be drinking when compared to some previous estimates, there is still a large number of heavy drinkers. In addition, traditional demographic variables continue to predict alcohol consumption levels. Students also report a similar variety of drinking related problems as in previous college drinking studies. Women constitute half as many heavy drinkers as men, but report an equal amount of alcohol-related problems in this sample. When controlling for race, it appears that white students continue to drink the most, and show heavy drinking rates comparable to a previous large college sample in the northeast. Students who live on campus drink more than their commuting counterparts, and the drinking age has little effect on consumption levels or total reported alcohol-related problems, although it alters the context of drinking somewhat. Findings are generally compared to previous as well as more recent college drinking data. Sex differences and similarities are discussed, as well as the findings concerning legal drinking status. Implications for prevention efforts are suggested. PMID- 2270063 TI - Family background of alcohol abuse and its relationship to alcohol consumption among college students: an unexpected finding. AB - The purpose of this study was to determine the possible association between positive family background of alcohol abuse (having a parent or grandparent who sometimes or often drank too much) and the amount of alcohol consumed per week among college students. It was additionally to determine the possible differences between students with positive, compared to students with negative, family backgrounds of alcohol abuse in regards to drinking patterns, using a survey instrument that indirectly measures family background for alcohol abuse. For this cross-sectional study, a quota sample of 971 college students from all four regions of the United States was selected. Results revealed no association between family history and mean amount of alcohol consumed per week for the total sample (r = .007), or for men (r = .04) or women (r = .02). Curve analysis indicated a slightly positively skewed curve for the total group and also for male and female students. A t test and chi-square analysis found no significant difference between positive and negative family backgrounds and mean amount of alcohol consumed or drinking patterns. Among those with positive family backgrounds there was no clustering on a scatter plot for either heavy or light amounts of alcohol consumed. The results showed remarkable similarity in alcohol consumption and drinking patterns between students who were classified as having a positive, as opposed to negative, family background. It was concluded that having a positive family background for heavy drinking was not associated with either light or heavy alcohol consumption among this national sample of college students. PMID- 2270064 TI - Adolescent drinking behavior: an observational study of the influence of situational factors on adolescent drinking rates. AB - Adolescent drinking behavior was observed on weekend nights (9 PM until midnight) in three youth bars, three youth centers and two discos located in the most southern part of the Netherlands. Drinking rates, individual characteristics, drinking group variables and aspects of the overall drinking situation were recorded. Boys and girls appeared to differ in the variables of influence on their drinking rates. Boys were observed to drink at a higher rate on evenings with loud music, when they participated in large, all-male groups and when their (estimated) age was less than 20. Together these variables explain 24% of the variance in boys' drinking rates. Girls drank less fast when they participated in a group not buying rounds and in a drinking group of constant composition. Although analysis showed that girls' drinking rates did not vary significantly with aspects of the overall situation and individual variables, still 14% of the total variance here could be explained by the drinking group variables. These results are to some extent consistent with findings from other observational studies on drinking behavior. Most of these studies showed males in large groups to drink at the highest rates. However, only a few observational studies were aimed exclusively at young people's drinking behavior and those studies did not include aspects of the overall drinking situation. PMID- 2270065 TI - Drinking styles of adolescents and young adults. AB - Drinking among adolescents and young adults has received more attention during the recent past, but little research has focused on the drinking styles that might characterize younger people. A typology of drinking behavior has special relevance for this group, since the adolescent years and young adult years are formative in the development of drinking habits. This study used a model that had been applied to "normal" drinking behaviors of adults. However, the set of drinking variables was expanded to cover a wider range of activities, and a second set of behaviors, intended to reflect potential "problem" drinking, were derived from the National Council on Alcoholism criteria for the diagnosis of alcoholism. The set of 55 "normal" drinking behaviors was factor analyzed, yielding a six-factor structure. The first four factors were quite similar to previous work on adult drinking styles, and the remaining two factors clearly related to the drinking of younger people. The "problem" drinking variables yielded a two-factor structure, one set consisting of serious but uncommon experiences and the second set consisting of less serious and more common experiences. Several of the "normal" drinking factors were significant predictors of the "problem" drinking scores, suggesting that certain styles of drinking are more likely than others to lead to later problems. PMID- 2270067 TI - Conversations for action. PMID- 2270066 TI - The sexual relationship of male alcoholics and their female partners during periods of drinking and abstinence. AB - The quality of the sexual relationship between alcoholic male veterans admitted to an alcohol treatment program and their stable nonalcoholic female partners was assessed in relation to time intervals of abstinence and drinking. Repeated measures analyses performed on the LoPiccolo Sexual History Form provided information on sexual problems associated with the desire, arousal and orgasm phases of the sexual response cycle and other kinds of information relevant to sexual functioning. Results indicate that the sexual relationship varies in relation to drinking or abstinence. Sexual intimacy appears quite normal and satisfactory during abstinent periods; however, female partners present an internally consistent picture of neither desiring nor enjoying sex during drinking periods, though accepting sex reluctantly. For male alcoholics, satisfaction with sex while drinking continues to be reported despite awareness of their partner's negative emotional reactions during sex. Clinicians and researchers are cautioned to differentiate drinking and abstinent periods when assessing the sexual relationship of alcoholic couples. PMID- 2270068 TI - Charity comes from the heart. PMID- 2270069 TI - Alcohol consumption and hangover. AB - Although many of us don't like to admit it, most of us have experienced the unmistakeable feeling of "the morning after." Dry mouth, nausea, dizziness, and headache are just a few of the consequences of overindulgence. Medically, this is known as acute alcohol withdrawal, but to us it's just a hangover. PMID- 2270070 TI - Vibrio infections in Kansas City. AB - In August 1989, the Kansas City Health Department declared vibrio infections a reportable disease. The authors present a report discussing cases of vibriosis reported between 1980 and 1989. PMID- 2270071 TI - The giant paraesophageal hernia: a particularly morbid condition of the esophageal hiatus. AB - The giant paraesophageal hernia is an uncommon but particularly morbid disorder of the gastroesophageal hiatus that may have life-threatening complications. The authors present three cases of these hernias to illustrate the potential complications of true hernias of the gastroesophageal hiatus. PMID- 2270072 TI - Magnetic resonance evaluation of infantile myofibromatosis. AB - Although infantile myofibromatosis is rare, it represents the most common fibrous tumor of infancy. The author presents a case where magnetic resonance imaging (MRI) was used to evaluate the tumor. PMID- 2270073 TI - Missouri State Medical Association 1990-91 policy manual. PMID- 2270075 TI - Inhibition of cell growth and stable DNA replication by overexpression of the bla gene of plasmid pBR322 in Escherichia coli. AB - A composite plasmid comprising the mini-F and pBR322 replicons was found to inhibit cell growth of a host with conditional mutations in dnaA and rnh under restrictive conditions, where the normal initiation of replication from oriC was inactivated, but the alternative replication initiation from oriK was active. It was further shown that the composite plasmid inhibited stable DNA replication (SDR) which occurs constitutively in cells mutant for rnh. Neither pBR322 nor mini-F alone produced these inhibitory effects. Deletion analyses revealed that the mini-F segment responsible for the inhibition of both processes was the promoter region of the sopA gene which had been cloned into a site upstream of the bla gene on pBR322 in such an orientation as to cause overexpression of bla. Inserting the promoter of the Escherichia coli lac gene into the same site had the same effect. Introduction of a deletion and a frameshift mutation into bla abolished the inhibition. Thus, the inhibition of growth and SDR appear to be due to overproduction of the bla gene product, beta-lactamase. PMID- 2270076 TI - Possible involvement of the ugpA gene product in the stable maintenance of mini-F plasmid in Escherichia coli. AB - The seg-3 mutant Escherichia coli does not support the maintenance of mini-F plasmid at 42 degrees C. We cloned the chromosomal DNA segment of the wild-type strain W3110 that complements the Seg- phenotype of this mutant. Cleavage mapping of this segment showed that it was derived from the 76-min region of the E. coli chromosome map. Complementation tests using plasmids carrying subcloned DNA segments suggested that the seg-3 mutant carried two mutations that additively affected the maintenance of mini-F plasmid; one was in the ugpA gene and the other was presumably in the rpoH gene. We generated a disrupted ugpA null mutant and found that the mini-F plasmid was unstable in this ugpA null mutant even at 30 degrees C. This suggests that the ugpA gene product is required for the stable maintenance of mini-F plasmid. PMID- 2270077 TI - Iron(III) hydroxamate transport of Escherichia coli: restoration of iron supply by coexpression of the N- and C-terminal halves of the cytoplasmic membrane protein FhuB cloned on separate plasmids. AB - Transport of iron(III) hydroxamates across the inner membrane into the cytoplasm of Escherichia coli cells is mediated by the FhuC, FhuD and FhuB proteins. We studied the extremely hydrophobic FhuB protein (70 kDa) which is located in the cytoplasmic membrane. The N- and C-terminal halves of the protein [FhuB(N) and FhuB(C)] show homology to each other and to the equivalent polypeptides involved in uptake of ferric dicitrate and of vitamin B12. Various plasmids carrying only one-half of the fhuB gene were expressed in fhuB- mutants. Only combinations of FhuB(N) and FhuB(C) polypeptides restored sensitivity to albomycin and growth on iron hydroxamates as sole iron source; no activity was obtained with either half of FhuB alone. These results indicate that both halves of FhuB are essential for substrate translocation and that they combine to form an active permease when expressed separately. In addition, a FhuB derivative with a large internal duplication of 271 amino acids was found to be partially active in transport, indicating that the extra portion did not perurb proper insertion of the active FhuB segments into the cytoplasmic membrane. PMID- 2270078 TI - A carrot cell variant temperature sensitive for somatic embryogenesis reveals a defect in the glycosylation of extracellular proteins. AB - The temperature-sensitive carrot cell variant ts11c, arrested in somatic embryogenesis after the globular stage, was characterized. The sensitivity to a shift from 24 degrees C (permissive temperature) to 32 degrees C (non-permissive temperature) is greatest at the globular stage of embryogenesis, while cells proliferating in unorganized fashion and plantlets are not affected. Embryogenesis in ts11c is also arrested at the permissive temperature by replacement of conditioned culture medium with fresh medium. The timing of sensitivity of ts11c to medium replacement coincides with the sensitivity to temperature shift. Both sensitivities are recessive in somatic hybrids between ts11c and wild-type cells. Extracellular glycoproteins synthesized by ts11c at the non-permissive temperature contain much less fucose than those synthesized by the wild type. The glycoproteins synthesized by the variant under non-permissive conditions do not accumulate at the periphery of the embryo, as their wild-type counterparts do, but instead show a diffuse distribution throughout the embryo. The defect in ts11c can be fully complemented by the addition of extracellular wild-type proteins. A revertant of ts11c was isolated that simultaneously reacquired temperature insensitivity and normal glycosylation ability. Collectively, these observations indicate that ts11c is not able to perform proper glycosylation at the non-permissive temperature and suggest that the activity of certain extracellular proteins, essential for the transition of globular to heart stage somatic embryos, depends on the correct modification of their oligosaccharide side-chains. PMID- 2270079 TI - Identification of CBS2 as a mitochondrial protein in Saccharomyces cerevisiae. AB - The nuclear genome encoded yeast protein CBS2 is required for translational activation of mitochondrial cytochrome b RNA. Genetic studies have shown that the target sequence of the CBS2 protein is the 5' untranslated leader sequence of cytochrome b RNA. Here we report on the intracellular localization of CBS2. CBS2 protein, expressed in Escherichia coli and prepared from inclusion bodies, was used as an antigen to raise a polyclonal rabbit antiserum. Affinity-purified CBS2 antibodies detect a 45 kDa protein in mitochondrial lysates of wild-type cells, which is absent in a strain in which the CBS2 gene has been deleted. The protein is overexpressed in mitochondrial extracts of a transformant carrying the CBS2 gene on a high copy number plasmid, but undetectable in the post-mitochondrial supernatant. Intramitochondrial localization of CBS2 was verified by in vitro import of CBS2 protein that had been synthesized in a reticulocyte lysate programmed with CBS2 mRNA transcribed in vitro. Mitochondrial import of CBS2 is not accompanied by any detectable proteolytic processing. PMID- 2270080 TI - cis regulatory elements directing tuber-specific and sucrose-inducible expression of a chimeric class I patatin promoter/GUS-gene fusion. AB - The 5'-upstream region of the class I patatin gene B33 directs strong expression of the beta-glucuronidase (GUS) reporter gene in potato tubers and in leaves treated with sucrose. Cis-acting elements affecting specificity and level of expression were identified by deletion analysis in transgenic potato plants. A putative tuber-specific element is located downstream from position -195. Nuclear proteins present in leaf and tuber extracts bind specifically to a conserved AT rich motif within this region. A DNA fragment between -183 and -143, including the binding site is, however, not able to enhance the expression of a truncated 35S promoter from cauliflower mosaic virus. Independent positive elements contributing to a 100-fold increase relative to the basic tuber-specific element are located between -228 and -195; -736 and -509, -930 and -736 and -1512 and 951. Sucrose inducibility is controlled by sequences downstream of position -228, indicating that the tuber-specific and sucrose-inducible elements are in close proximity. PMID- 2270081 TI - DNA sequence elements required for transcription initiation of the Schizosaccharomyces pombe ADH gene in Saccharomyces cerevisiae. AB - The roles of the TATA element and sequences near the mRNA initiation site in specifying the location of initiation sites in Saccharomyces cerevisiae were examined, using the Schizosaccharomyces pombe ADH gene. The importance of spacing was demonstrated by analysis of a series of deletions that removed from 8-50 bp between the TATA element and ATG translation initiation site of this gene. Primer extension mapping showed that increasing deletion length is associated with a progressive shift downstream in the location of the initiation sites. The distance of a given site from the promoter affected the relative ability of the site to be utilized for initiation. For this gene, a permissive region for transcription initiation exists between 55 and 125 bases downstream of the TATA element, and a zone of 75-115 bases allows maximal usage of an initiation site. The presence of a TATA sequence was shown to be necessary in S. cerevisiae for maintaining the location of this "window" of initiation. The TATA sequence is essential for function of the gene in S. pombe. This gene, as well as the majority of the 63 S. cerevisiae genes surveyed, uses initiation sites which fit a PyAA/T(Pu) consensus. Cis-acting mutations were recovered which restored ADH activity to a deletion allele that initiates its mRNAs downstream of the ATG. DNA sequence and transcript analysis with these mutants confirmed the requirement of proper spacing and conformity of initiation sites to the PyAA/T(Pu) consensus for efficient transcript initiation. PMID- 2270082 TI - Trans-splicing mutants of Chlamydomonas reinhardtii. AB - In Chlamydomonas reinhardtii the three exons of the psaA gene are widely scattered on the chloroplast genome: exons 1 and 2 are in opposite orientations and distant from each other and from exon 3. The mature mRNA, encoding a core polypeptide of photosystem I, is thus probably assembled from separate precursors by splicing in trans. We have isolated and characterized a set of mutants that are deficient in the maturation of psaA mRNA. The mutants belong to 14 nuclear complementation groups and one chloroplast locus that are required for the assembly of psaA mRNA. The chloroplast locus, tscA, is remote from any of the exons and must encode a factor required in trans. The mutants all show one of only three phenotypes that correspond to defects in one or other or both of the joining reactions. These phenotypes, and those of double mutants, are consistent with the existence of two alternative splicing pathways. PMID- 2270083 TI - Mutant of the glutamine transfer RNA gene as UGA suppressor in Escherichia coli. AB - A UGA suppressor derived from a glutamine tRNA gene of Escherichia coli K12 was isolated and characterized. Phages carrying the suppressor su+2UGA could be obtained only from a hybrid transducing phage, h80cI857psu+2oc, but not from the original transducing phage lambda cI857psu+2oc. By DNA sequence analysis, it was found that the su+2 UGA suppressor obtained has two mutations; one is in the anticodon (TTA----TCA), as expected, and the other (C----T) is at the 7th position from the 3' end of tRNA(2Gln). The significance of these mutations and the lethal effect on phage lambda of the increased amounts of UGA suppressor tRNAs are discussed. PMID- 2270084 TI - Transcription of two divergently transcribed yeast genes initiates at a common oligo(dA-dT) tract. AB - Oligo(dA-dT) tracts are frequently found in the intergenic regions of the yeast Saccharomyces cerevisiae and have been proposed to act as upstream promoter elements for constitutive transcription. An oligo(dA-dT) tract of 23 bp is also found as a characteristic sequence motif in the centre of the 230 bp segment which separates the open reading frames of the CBS2 gene and its 5'-flanking gene on chromosome IV. Recently we have reported that transcription of CBS2 is initiated immediately adjacent to this oligo(dA-dT) tract (michaelis et al. 1988). Here we report that the flanking gene of unknown function is divergently transcribed into an RNA with heterogeneous 5' ends. Two of these 5' ends map within the oligo(dA-dT) stretch, while the third is located upstream, leading to an RNA species which is partially complementary to the CBS2 transcript. Gel shift assays show that the oligo(dA-dT) stretch is specifically recognized by (a) binding factor(s) in nuclear extracts. We discuss these results with respect to the role of oligo(dA-dT) stretches in gene expression in yeast. PMID- 2270085 TI - TUF factor binds to the upstream region of the pyruvate decarboxylase structural gene (PDC1) of Saccharomyces cerevisiae. AB - The upstream activation site of the pyruvate decarboxylase gene, PDC1, of Saccharomyces cerevisiae contains an RPG box, and mediates the increase in expression of a PDC1-lacZ fusion gene during growth on glucose. Oligonucleotide replacement experiments indicate that the RPG box functions as an absolute activator of expression, but other elements (possibly CTTCC repeats) are required for carbon source regulation, and maximal expression. Gel retardation and oligonucleotide competition experiments suggest that the DNA binding factor TUF interacts with the RPG box in the upstream region of PDC1. Binding of TUF factor is not carbon source dependent in in vitro experiments, and is probably not responsible for glucose induction of PDC1 expression. PMID- 2270086 TI - Agrobacterium plasmids encode structurally and functionally different loci for catabolism of agrocinopine-type opines. AB - Agrobacterium tumefaciens strains C58, T37, K827 and J73, A. rhizogenes strains A4 and 15834, and A. radiobacter strain K299 were all susceptible to agrocin 84 and this sensitivity was enhanced in each case by addition of agrocinopines A and B. Analysis of transconjugants showed that sensitivity of strain A4 to agrocin 84 was encoded by pArA4a and not by the rhizogenic plasmid, pRiA4. The acc region of the A. tumefaciens nopaline-type Ti plasmid pTiC58, contained on the recombinant plasmid pTHH206, hybridized strongly to restriction fragments of plasmids from strains T37, K827, J73 and K299. Hybridizing fragment patterns generated with BamHI and EcoRI were identical among the four Ti plasmids while pAtK299 showed restriction fragment length polymorphisms at acc with the two enzymes. At moderate stringency, the pTiC58 acc region hybridized weakly to a single restriction fragment from the Ar plasmid of A. rhizogenes strain A4, but not to pTiBo542, which encodes catabolism of the closely related opines agrocinopines C and D. Plasmid pAtK84b of A. radiobacter strain K84 is induced for conjugal transfer by agrocinopines A and B. However, no hybridization was detected between this plasmid and acc from pTiC58 under conditions of moderate stringency. Like pTiC58, pAtK84b conferred transport of agrocinopines A and B on its host bacteria despite the absence of detectable sequence homology with the pTiC58-derived acc probe. However, unlike pTiC58, pAtK84b failed to confer sensitivity to or uptake of agrocin 84 on its bacterial host. These results indicate that at least four distinguishable systems exist for catabolism of the two agrocinopine opine families with the prototype locus, exemplified by acc from pTiC58, being strongly conserved among nopaline-type Ti plasmids. PMID- 2270087 TI - Deletion analysis of the ARG4 promoter of Saccharomyces cerevisiae: a poly(dAdT) stretch involved in gene transcription. AB - Transcription of the ARG4 gene of Saccharomyces cerevisiae is regulated by general control of amino acid biosynthesis but not by a specific regulatory mechanism. Three deletion mutants (delta I, delta II, delta III) successively removing DNA sequences upstream from the coding sequence have been phenotypically analyzed after insertion into a single copy plasmid. As expected, delta I, which lacks the sequences upstream to -155, including the two putative upstream activation sequences (UAS), was unable to derepress argininosuccinate lyase biosynthesis under conditions of amino acid starvation. In delta II (deleted up to -126) the enzyme activity was very low and cells harbouring this allele were arginine dependent. These drastic phenotypic changes can be attributed to the loss of 12 out of 14 dA residues from positions -124 to -137. This poly (dAdT) sequence most likely serves as an upstream promoter element for constitutive expression of ARG4. The delta III deletion removes all 5' sequences including the putative TATA box. This inactive allele has been successfully used for selecting yeast promoters of unknown origin. PMID- 2270088 TI - DNA sequence analysis of spontaneous histidine mutations in a polA1 strain of Escherichia coli K12 suggests a specific role of the GTGG sequence. AB - Spontaneously arising histidine mutations in an Escherichia coli K12 strain deficient for DNA polymerase I were analysed at the DNA sequence level. We screened approximately 150,000 colonies and isolated 106 histidine auxotrophs. Of these, 98 were unstable hisC mutations; 12 representative mutants analysed were shown to have arisen by the excision of a single quadruplet repeat in the sequence 5'-GCTGGCTGGCTGGCTG-3'. Of the eight mutations at other sites, three hisA deletions and one hisD deletion occurred as a consequence of misalignment of tandemly repeated pentamers (hisD) or decamers (hisA). A single hisA point mutation was found to be a missense mutation. Two extended deletions, covering the his operon were not analysed. We could not identify the hisC deletion by sequencing. We conclude that polA1 is a strong mutator that induces mutations mostly of the minus frameshift and deletion type by a Streisinger-type of mispairing in repetitive DNA sequences. Finally, the possible role of a 5'-GTGG 3' sequence and its inverted or direct complements, which are found in the vicinity of all the deletions and frameshifts, is discussed. PMID- 2270089 TI - The glutamate dehydrogenase structural gene of Escherichia coli. AB - The glutamate dehydrogenase structural gene, gdhA, was mapped at 38.6 min on the genetic map and at 1860 kb on the physical map. A detailed map of this region is presented. PMID- 2270090 TI - Formation of mutagens during the frying of Hawaiian fish: correlation with creatine and creatinine content. AB - Compounds mutagenic toward Salmonella typhimurium strain TA98 in the presence of rat-liver homogenates (S9) were formed when fish flesh was fried at 199 degrees C. Three species of Hawaiian fish commonly consumed in Hawaii (skipjack tuna, Katsuwonus pelamis; yellowfin tuna, Neothunnus macropterus; and milkfish, Chanos chanos) were cooked in an electric skillet, along with samples of sole (Microstomus pacificus). Organic extracts of the fish were tested in the Ames Salmonella mutagenic assay using tester strain TA98 and S9. Basic organic extracts of fried, but not raw, samples exhibited significant mutagenicity. The levels of mutagenicity were also higher among the red flesh Hawaiian fish ('ahi, aku and awa) than with the white flesh sole. Creatine and creatinine contents were highest in the Hawaiian fish and lower in the sole. Creatine levels in the fish were 50-100 times greater than the creatinine content and varied from a high of 645 mg/100 g wet weight of fish for yellowfin tuna to a low value of 251 mg/100 g for sole. Mutagen levels are only approximately related to creatine/creatinine levels suggesting that other components contained in these fish may be as important as the guanidines in determining the levels of mutagen in the cooked fish. PMID- 2270091 TI - DNA strand breaks in liver for four aliphatic epoxides in mice. AB - Four aliphatic epoxides, 1-naphthyl glycidyl ether (NGE), 1-naphthylpropylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE), 3,3,3-trichloropropylene oxide (TCPO) and two of their precursors, 1-allylnaphthalene (AN) and 3,3,3 trichloropropylene (TCP), were selected for DNA strand-break analysis in liver in vivo with mice. The four epoxides selected were among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test and had been evaluated for their in vivo genotoxicity as measured by sister chromatid exchange (SCE) and chromosome aberrations (CA). A significant increase in the percentage of unwound DNA was observed at a 4-h exposure time for all the compounds at high doses except for AN. TCPO, the least genotoxic compound in bone marrow, had the greatest liver toxicity after 1-h exposure while NGE showed the most toxicity after 6 h. As might be expected from their corresponding epoxides, AN but not TCP exhibited significant SCE activity in the bone marrow of mice. This study reemphasizes the importance of evaluating the stability of direct acting alkylating agents in comparing test results and in establishing the relative order of genotoxicity for such compounds. PMID- 2270092 TI - Molecular analysis of hprt mutants induced by 2-cyanoethylene oxide in human lymphoblastoid cells. AB - The mutagenic epoxide metabolite of acrylonitrile, 2-cyanoethylene oxide (ANO), was used to treat human TK6 lymphoblasts (150 microM x 2 h ANO). A collection of hypoxanthine-phosphoribosyltransferase (hprt) mutants was isolated and characterized by dideoxy sequencing of cloned hprt cDNA. Base-pair substitution mutations in the hprt coding region were observed in 19/39 of hprt mutants: 11 occurred at AT base pairs and 8 at GC base pairs. Two -1 frameshift mutations involving GC bases were also observed. Approximately half (17/39) of the hprt mutants displayed the complete loss of single and multiple exons from hprt cDNA, as well as small deletions, some extending from exon/exon junctions. Southern blot analysis of 5 mutants with single exon losses revealed no visible alterations. Analysis of 1 mutant missing exons 3-6 in its hprt mRNA revealed a visible deletion in the corresponding region in its genomic DNA. The missing exon regions of 4 mutants (one each with exons 6, 7 and 8 loss and one mutant with a 17-base deletion of the 5' region of exon 9) were PCR amplified from genomic DNA and analyzed by Southern blot using exon-specific probes. The exons missing from the hprt mRNA were present in the genomic hprt sequence. DNA sequencing of the appropriate intron/exon regions of hprt genomic DNA from a mutant with exon 8 loss and a mutant exhibiting aberrant splicing in exon 9 revealed point mutations in the splice acceptor site of exon 8 (T----A) and exon 9 (A----G), respectively. PMID- 2270093 TI - Study on mutagenicity and antimutagenicity of BHT and its derivatives in a bacterial assay. AB - The mutagenicity of butylated hydroxytoluene (BHT) and its derivatives was investigated by the Ames method using Salmonella typhimurium TA98 and TA100 with or without S9 mix. The compounds were not mutagenic in either indicator strain at concentrations ranging from 50 to 330 micrograms/plate (SQ: 3,5,3',5'-tetra-tert butylstilbenequinone; VI-III: unidentified), 500 micrograms/plate (BE: 3,5,3',5' tetra-tert-4,4'-dihydroxy-1,2-diphenylethylene; VI: 2,6-di-tert-butyl-4-methyl-4 tert-butylperoxy-2,5-cyclohexadienone ; VI-I: unidentified; VI-II: 3-acetyl-2,5 di-tert-cyclopenta-2,4-dienone) and 1000 micrograms/plate (BHT). The antimutagenic effects of BHT and its derivatives on mutagenesis by chemical agents were investigated in Salmonella typhimurium TA98 and TA100 and Escherichia coli WP-2 hcr-. VI-II suppressed the mutagenesis induced in TA98 and TA100 by 2 (2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2) and that induced in WP-2 hcr- by 4-nitroquinoline-1-oxide (4NQO) without decreasing cell viability. In WP-2 hcr-, the mutagenesis induced by AF-2 and ethyl methanesulfonate was also suppressed significantly. Mutations induced by methyl methanesulfonate were slightly inhibited. However, VI-II had no effect on the mutagenesis induced by N-methyl-N' nitro-N-nitrosoguanidine. PMID- 2270094 TI - Induction of morphological transformation by coal-dust extract in BALB/3T3 A31-1 13 cell line. AB - The transforming activity of coal dust extracts was studied using BALB/3T3 clone A31-1-13 cells. Coal-dust extracts, both nitrosated and nonnitrosated, induced cell transformation in a dose-response manner. However, the transformation frequency was higher with the nitrosated than with the nonnitrosated extract. All transformed cell lines derived from coal-dust extract-induced foci showed biological characteristics of neoplastic transformation such as loss of contact inhibition and anchorage-independent growth. These results appear to support a hypothesis of coal mine dust causation of gastric cancer in coal miners. PMID- 2270095 TI - The detection of mitotic and meiotic chromosome gain in the yeast Saccharomyces cerevisiae: effects of methyl benzimidazol-2-yl carbamate, methyl methanesulfonate, ethyl methanesulfonate, dimethyl sulfoxide, propionitrile and cyclophosphamide monohydrate. AB - The diploid yeast strain BR1669 was used to study induction of mitotic and meiotic chromosome gain by selected chemical agents. The test relies on a gene dosage selection system in which hyperploidy is detected by the simultaneous increase in copy number of two alleles residing on the right arm of chromosome VIII: arg4-8 and cup1S (Rockmill and Fogel. 1988; Whittaker et al., 1988). Methyl methanesulfonate (MMS) induced mitotic, but not meiotic, chromosome gain. Methyl benzimidazol-2-yl carbamate (MBC) and ethyl methanesulfonate (EMS) induced both mitotic and meiotic chromosome gain. Propionitrile, a polar aprotic solvent, induced only mitotic chromosome gain; a reliable response was only achieved by overnight incubation of treated cultures at 0 degrees C. MBC is postulated to act by binding directly to tubulin. The requirement for low-temperature incubation suggests that propionitrile also induces aneuploidy by perturbation of microtubular dynamics. The alkylating agents MMS and EMS probably induce recombination which might in turn perturb chromosome segregation. Cyclophosphamide monohydrate and dimethyl sulfoxide (DMSO) failed to induce mitotic or meiotic chromosome gain. PMID- 2270096 TI - Genotoxic activity of a tobacco-specific nitrosamine. PMID- 2270097 TI - No. 22. Prevalence of carcinogens and short-term test performance--a dangerous statistical illusion? PMID- 2270098 TI - Biochemical and immunochemical characterization of 125I-labeled cuticle components of Haemonchus contortus. AB - Live Haemonchus contortus developmental stages were radioiodinated and then subjected to a stepwise extraction procedure consisting of a buffer extract (with or without detergent) to solubilize putative surface-associated antigenic macromolecules, followed by a detergent/beta-mercaptoethanol (BME) extract to solubilize putative cuticle collagen proteins. A buffer-extracted iodinated 100 kDa protein was present in the free-living, infective L3(2M) stage. This labeled protein was released during in vitro exsheathment of L3(2M) and was not present in the ecdysed second molt (2M) cuticle. In addition to the 100-kDa protein, exsheathment fluid contained a 70-kDa labeled protein that was not extracted from iodinated L3(2M) with either detergent or BME. The data suggest that these proteins are components of the specialized ring portion of the 2M cuticle that is enzymatically ruptured during ecdysis. The L3(2M) and the exsheathed third-stage larvae (L3) contained 3 labeled, BME-extracted, collagenase-sensitive proteins of 108, 88 and 53 kDa. In contrast, four detergent-extracted, collagenase insensitive, iodinated proteins (143, 81, 58 and 30 kDa) were present in adult H. contortus. The 143-kDa protein was both glycosylated and immunogenic. All 4 adult cuticle proteins were released from the cuticle surface into culture fluids. Furthermore, a cysteine protease was secreted by adults which apparently hydrolyzed the released 81-, 58- and 30-kDa surface proteins. PMID- 2270099 TI - Molecular cloning and expression of an immunodominant 53-kDa excretory-secretory antigen from Trichinella spiralis muscle larvae. AB - A Trichinella spiralis cDNA expression library was constructed in lambda gt11 from muscle larvae mRNA and immunologically screened to identify genes encoding previously described immunodiagnostic excretory-secretory (ES) antigens. Screening the library with T. spiralis infection serum from swine or rabbit antiserum to T. spiralis ES antigen identified one clone, designated TsA-12, that contains a cDNA transcript 539 bp in length and codes for an apparent 123-kDa beta-galactosidase fusion protein that does not cross-react with Trichuris suis or Ascaris suum infection serum. Western blots of T. spiralis extracts and immunoperoxidase staining of tissue sections from muscle larvae using antibodies to purified TsA-12 demonstrate homology between TsA-12 and the 53 kDa diagnostic antigen from ES products (designated Ts.53) and localize the homologous native antigen to the stichocyte cells of the parasite. ELISA tests using TsA-12 as antigen, detected antibodies to T. spiralis in experimentally-infected mice as early as 14 days post-inoculation with maximum antibody titers being reached at 28 days post-inoculation. The TsA-12 dscDNA hybridizes to mRNA sequences expressed in both the muscle larvae and adult stages; however, concomitant expression of the native antigen is not observed within adult ES products. Southern blots of homologous and heterologous genomic DNAs probed with 32P labeled TsA-12 dscDNA fragments verify TsA-12 as a T. spiralis specific sequence that is present in multiple copies within the parasite genome. PMID- 2270100 TI - Schizodeme analysis of Trypanosoma cruzi stocks from South and Central America by analysis of PCR-amplified minicircle variable region sequences. AB - Kinetoplast DNA (kDNA) was isolated from 56 stocks of Trypanosoma cruzi isolated from human patients, animals and insects from Brazil, Venezuela, Colombia and Costa Rica. Comparison of the patterns of digested kDNA on acrylamide gels led to the grouping of several stocks into two schizodemes. Schizodeme analysis was also performed using a set of 330-bp fragments representing all the variable regions of the minicircle DNA molecules, which were obtained by PCR amplification of the kDNA using conserved region primers. The results of this analysis were consistent with the analysis using total kDNA, but the more informative restriction profiles allowed the construction of additional schizodemes. In addition, two oligomers were generated from variable region sequences of cloned minicircles from a Y and a Cl strain, and these were used as schizodeme-specific probes to detect homologous sequences in the amplified minicircle DNAs. The results indicate that a combination of restriction enzyme fingerprinting and hybridization of amplified variable region minicircle DNA with schizodeme-specific probes can be used for both sensitive detection and classification of T. cruzi. PMID- 2270101 TI - The gene product of the Plasmodium falciparum 11.1 locus is a protein larger than one megadalton. AB - The Plasmodium falciparum 11.1 gene locus on chromosome 10 extends over 30 kb and contains approximately 22 kb of a tandemly repeated 27-bp sequence. Biochemical and size similarities have been noted between the reported 11.1 antigen and a variable-Mr, surface-radioiodinatable protein which appears to be involved in the cytoadherence of red blood cells infected with mature intraerythrocytic parasites to venular endothelium. We attempted to determine if these proteins were identical. Using rabbit antibody and affinity purified human immune sera specific for peptides encoded by the 27-bp repeat and a flanking 5' region, we have shown that the 11.1 locus encodes a protein of more than 1000 kDa. This protein cross reacts with an uncharacterized 260-kDa protein, previously identified as the gene product of the 11.1 locus, and Pf155-RESA, but not with the radioiodinatable protein. The 11.1 protein that we have identified is a malarial protein of unprecedented size. PMID- 2270102 TI - Active transport of 2-deoxy-D-glucose in Trypanosoma brucei procyclic forms. AB - The characteristics of glucose transport by procyclic forms of Trypanosoma brucei were examined in a rapid transport assay using the glucose analogue 2 deoxyglucose. In contrast to bloodforms where the Km for 2-deoxyglucose transport is about 1 mM, procyclic forms have a Km of about 38 microM. Procyclic forms show temperature-dependent, saturable import, and import of 2-deoxyglucose is competitive with glucose and mannose. Unlike the bloodforms which employ facilitated diffusion, the procyclic forms actively transport glucose. Use of inhibitors and ionophores suggests that a protonmotive force is required for glucose transport in procyclic forms. Unlike the human erythrocyte glucose transporter, the glucose transporter of the T. brucei procyclic form is relatively insensitive to inhibition by cytocholasin B. PMID- 2270103 TI - Strategies for detoxification of aldehydic products of lipid peroxidation in helminths. AB - Crude extracts from a number of helminths including Schistosoma intercalatum and Fasciola hepatica were able to detoxify known aldehydic products of lipid peroxidation. A major route for alk-2-enal and alka-2,4-dienal detoxification in parasitic helminths was via glutathione conjugation and glutathione transferase appeared to be responsible for the activity. As yet uncharacterised NADPH-linked systems may provide an important secondary pathway for detoxification of alk-2 enals and alka-2,4-dienals in parasitic helminths. The free-living nematode Panagrellus redivivus had higher active NADH/NADPH-linked aldehyde reduction systems compared to parasitic helminths. The NADH linked and NADPH linked reductions in P. redivivus were mitochondrial and cytosolic activities respectively. NADH/NADPH-linked systems may be responsible for alkanal reduction in helminths as there is no evidence of conjugation of alkanals with glutathione. P. redivivus and Haemonchus contortus were also able to oxidise aldehydes via NAD/NADP-linked systems. PMID- 2270104 TI - Chromosomal localization of seven cloned antigen genes provides evidence of diploidy and further demonstration of karyotype variability in Trypanosoma cruzi. AB - The karyotype of Trypanosoma cruzi was studied by pulsed field gel electrophoresis (PFGE) in conditions that allowed 20-25 chromosome bands to be detected. However, several of these bands were present in non-equimolar amounts, suggesting that the total chromosome number is considerably higher. The patterns obtained with the different cloned and uncloned strains were unique, suggesting that the karyotype of T. cruzi is highly variable. The chromosomal localizations of seven cloned genes were determined by Southern blotting of PFGE-separated chromosomes. Three of the clones gave rise to similar patterns and mapped on a chromosome or a family of chromosomes larger than 1.6 Mb. Two clones mapped on either single or pairs of chromosomes, which in some cases differed considerably in size between the different strains tested, suggesting that extensive chromosome rearrangements occur in T. cruzi. Another clone hybridized to several chromosomes in most strains and probably represents a family of genes. Lastly, one clone hybridized to nearly all chromosomes. Many of the clones hybridized to pairs of restriction fragments in the different strains, suggesting that they are allelic. For one of the clones it was possible to provide further evidence for the allelic nature of the fragments by establishing detailed restriction maps around them and by showing that the two fragments in a pair hybridized to chromosomes which differed slightly in size. Taken together, the results infer that the genome of T. cruzi epimastigotes is diploid. PMID- 2270105 TI - The lower-molecular-weight protein complex (RI) of the Plasmodium falciparum rhoptries lacks the glycolytic enzyme aldolase. AB - The gene for the Plasmodium falciparum glycolytic enzyme aldolase (PfA) has been cloned. Since polyclonal antibodies raised to an affinity-purified preparation of an approximately 41-kDa parasite rhoptry protein were used to isolate this clone, and its nucleotide sequence was verified using amino acid sequence information generated from the purified 41-kDa protein, the authors concluded that this rhoptry protein was PfA. In the present report, monoclonal antibodies which immunoprecipitate those rhoptry protein complexes containing 39-kDa (p39) and 37 kDa proteins (p37) were used along with PfA-specific polyclonal antibodies to further examine this conclusion. The electrophoretic mobilities of PfA and the rhoptry proteins in the presence of sodium dodecyl sulfate differed from each other in both reducing and nonreducing conditions after immunoprecipitation with these antibodies. Lysates of P. falciparum-infected erythrocytes contained abundant aldolase activity which was removed by anti-PfA antibodies. However, no aldolase activity was associated with affinity-purified rhoptry proteins. Controlled proteolysis with the endoproteinase V8 protease generated different digestion patterns for PfA, p39, and p37. While both PfA and the rhoptry proteins were components of multimeric protein complexes, as demonstrated by sucrose gradient centrifugation, their cellular localization patterns were quite different. These results demonstrate that PfA and the rhoptry-associated proteins p39 and p37 are different entities. PMID- 2270106 TI - Identification of the gene for a Plasmodium yoelii rhoptry protein. Multiple copies in the parasite genome. AB - Serum from mice hyperimmune to Plasmodium yoelii was used to screen a P. yoelii genomic DNA library. Antibodies selected from hyperimmune serum by lambda gt11 clone J7 or raised against a specific fusion protein or peptide produced a punctate pattern of immunofluorescence on fixed smears of parasitised erythrocytes and immunoprecipitated a 235-kDa protein apparently identical to a rhoptry protein previously implicated in red cell invasion. The cloned DNA hybridised to at least seven RsaI fragments of P. yoelii genomic DNA and to three DraI fragments of similar but not identical sequence. These results suggest that the gene encoding the 235-kDa rhoptry protein may be represented more than once in the P. yoelii genome. PMID- 2270107 TI - Sequence analysis and transcriptional activation of heat shock protein 83 of Leishmania mexicana amazonensis. AB - Changes in environmental temperature regulate the differential expression of genes during Leishmania stage differentiation. Therefore, molecular analysis of the heat shock proteins (HSPs) in these parasites is of interest as a model for thermoregulation of gene expression. Sequences of the HSP83 repetitive unit in the genome of Leishmania mexicana amazonensis, including both the coding and intergenic regions, are described. The 5' boundary of the message was mapped by S1 analysis, to potential AG splice sites located 293, 295 and 321 nucleotides upstream of the first ATG. A high degree of conservation (84%) is present between the coding sequence of HSP83 from L. mexicana amazonensis and similar sequences from Trypanosoma cruzi. The intergenic leishmanial sequences, however, were not homologous to similar sequences from HSP83 of trypanosomes, or from HSP70 of Leishmania major. A search for sequences that resemble eukaryote thermoregulated promoters was made and several regions with dyad symmetry were detected. However, only one of these regions was partially homologous with the consensus heat shock element present upstream of all eukaryotic HSPs studied to date. PMID- 2270108 TI - Characterisation of three groups of cysteine proteinases in the amastigotes of Leishmania mexicana mexicana. AB - The multiple cysteine proteinases characteristic of the amastigote forms of Leishmania mexicana mexicana have been shown to be of three types. The groups of enzymes are distinguished by their substrate specificities and physical properties and have been purified free from other proteinases and most other proteins. One group (A) comprises at least four enzymes that bind to Con A. The cysteine proteinases comprising the other two groups (B and C) were separated by ion exchange chromatography. These last two groups of enzymes show different specificities towards a range of peptidyl aminomethylcoumarins. Notably, the two group C proteinases are more active towards compounds with a basic amino acid in the P1 position, whereas the three enzymes of group B are as active towards substrates with tyrosine in this position. All the cysteine proteinases show preference for compounds with bulky amino acids at positions P2 and P3 and all are equally susceptible to a range of inhibitors characteristically active against cysteine proteinases. Other proteinases present in amastigotes of L. m. mexicana were shown to differ significantly from the cysteine proteinases with respect to their substrate preferences and susceptibility to inhibitors. PMID- 2270109 TI - D-lactate production in erythrocytes infected with Plasmodium falciparum. AB - The production of D-lactate that accompanies the metabolism of glucose to L lactate in Plasmodium falciparum was evaluated with erythrocytes that contained either young or mature parasites. Infected cells with ring-stage parasites release L-lactate and D-lactate at rates 1340 and 81 nmol h-1 (10(8) cells)-1, respectively. These rates increase to 2050 and 136 nmol h-1 (10(8) cells)-1, respectively, in infected cells with trophozoite/schizont-stage parasites. D Lactate represents 6-7% of the total lactate. The formation of D-lactate is by way of a methylgloxal pathway in which methylglyoxal is formed nonenzymatically from dihydroxyacetone phosphate and is then converted into D-lactate by the sequential action of parasite glycoxalase I and glyoxalase II. The kinetic properties of parasite glyoxalase I and glyoxalase II allow these enzymes to be distinguished from those in the host cell. D-Lactate production by the parasite appears to be a defense mechanism to protect the parasite from the toxic effects of methylglyoxal. PMID- 2270110 TI - Analysis of variation in PF83, an erythrocytic merozoite vaccine candidate antigen of Plasmodium falciparum. PMID- 2270111 TI - The structure of a galactofuranose-containing oligosaccharide isolated from glycoproteins of the trypanosomatid Herpetomonas samuelpessoai. PMID- 2270112 TI - An allele of Trypanosoma brucei cytoplasmic phosphoglycerate kinase is a mosaic of other alleles and genes. PMID- 2270113 TI - [Psychological sequelae of awareness in general anesthesia]. PMID- 2270114 TI - [Racemic therapeutic agents; problems concerning medical ethics and registration]. PMID- 2270115 TI - [Changes in medical attitude concerning sexuality and procreation in the past 50 years]. PMID- 2270116 TI - [Winter depression and light therapy]. PMID- 2270117 TI - [The prospective course of the AIDS epidemic in The Netherlands according to Farr's Law]. AB - In 1840 William Farr published his 'Laws of Epidemics' which he applied in 1866 to predict the cresting of an epidemic of rinderpest in England. Early in 1990 Bregman and Langmuir used these laws to predict the course of the AIDS epidemic in the U.S.A. They concluded that this epidemic had crested in 1988-1989. Applying the same method to the yearly number of AIDS patients in the Netherlands, the epidemic would peak around 1990-1991; thereafter the epidemic would decrease in volume to a low endemic level. This prediction should not yet be used as the basis of any public health action or policy. Only when it becomes clear from the figures of the U.S.A. that the AIDS epidemic follows Farr's laws, can the prediction become the basis of further policy. The sole aim of the calculations is to demonstrate that there is a distinct possibility that the new AIDS epidemic obeys the 150 year old laws of William Farr. PMID- 2270118 TI - [Estimate of the number of HIV-seropositive persons in The Netherlands; implications for the evolution of the AIDS epidemic]. AB - In this article we estimate the total number of HIV seropositives in the Netherlands with an extended version of the Fast Back Calculation model. As a result we found between 5500 and 6500 seropositives for the end of 1987. This is considerably lower than earlier expectations. The distribution of incidence over time suggests that the HIV epidemic has passed its summit. We argue that the total number of HIV infected persons halfway 1990 lies somewhere between 7500 and 9000. With the estimated number of HIV seropositives we also predict minimum values for the AIDS incidence in future years. We expect the number of new AIDS cases to increase to over 600 per year in the mid-nineties. We briefly discuss the consequences of our findings for AIDS control. We underline the desirability of a policy directed at risk groups and apart from continuing existing preventive measures aimed at these groups we advocate paying more attention to i.v. drug users, visitors of STD clinics and travellers to and applicants for political asylum from endemic areas. PMID- 2270119 TI - [Prognosis concerning HIV-infection and AIDS epidemic in The Netherlands based on mathematical analysis]. AB - In the Netherlands by the 1st of January 1990 1074 AIDS patients have been reported to the Department of the Chief Medical Officer. In the last few years the proportion of intravenous drug users increased and the proportion of homo/bisexual men decreased. After adjustment for the effect of delay in reporting the total number of AIDS patients by 1st January 1990 is estimated to be 1173. It appears that the reporting delay outside Amsterdam is longer than in this city. The time required for doubling of the half-yearly incidence of new AIDS patients (doubling time, dt) increased from 9 months in the beginning of the epidemic to 34 months. It is expected on the assumption of constant dt that 1120 new AIDS patients will be diagnosed in 1990 and 1991 together. The present growth among the homo/bisexual men (dt 34 months) is smaller than the one among the intravenous drug users (dt 23 months). The growth in Amsterdam (dt 36 months) is less than that in the rest of the Netherlands (dt 32 months). Based on the course of the AIDS epidemic the number of HIV infected (including the AIDS patients) is estimated as 9,000-12,000 by the 1st of January 1990. PMID- 2270120 TI - [Extension of the medical education through introduction of a general clinical education period?]. PMID- 2270121 TI - [A urological experience: patient in one's own hospital]. PMID- 2270122 TI - [Malignant melanoma in a primary care pathological-anatomical laboratory in 1988 and the year of the freckle bus 1989]. PMID- 2270123 TI - [Hyperthermia and crib death]. PMID- 2270124 TI - [Antiprogestagens]. PMID- 2270125 TI - [The significance of desensitization therapy]. PMID- 2270126 TI - [Oncological and endocrine administration of the antiprogestagen RU 486]. PMID- 2270127 TI - [Guideline in (suspected) malignant obstruction of the proximal bile ducts]. PMID- 2270128 TI - [Strongyloidiasis in former prisoners of war and internees in Southeast Asia during World War II]. AB - A survey was performed to estimate the prevalence of chronic strongyloidiasis among 145 Dutch ex-prisoners of war who had been working on the Burma-Thailand railway in 1943-1945, and 56 ex-internees in civil camps in the former Dutch East Indies. No infections were found in the latter group while in the Burma group 26 men (17.9%) had S. stercoralis larvae in their stools. Many of them suffered from larva currens, an urticarial skin disorder, cured by treatment. Examination of fresh stool specimens with the Baermann concentration technique gave better results than faecal cultures and microscopy of duodenal aspirate. Mean IgE level and eosinophil count were significantly higher in infected persons but the ranges are too wide to use these tests in diagnosing individual cases. PMID- 2270129 TI - [15 years of national screening for phenylketonuria in The Netherlands; 4th Report of the National Commission for Management of Phenylketonuria]. AB - In the period 1st September 1974 to 1st January 1989 2,511,000 infants (99.3% of all livebirths) were screened for PKU. Treatment was required in 158 of the 330 referred infants. The diagnosis of these 158 patients was PKU (137), hyperphenylalaninaemia (HPA) (19) and malignant HPA (2). Three cases had a false negative screening result. The prevalence of PKU, treated HPA and malignant HPA in the Netherlands is 1:18,000, 1:132,000 en 1:1,300,000. Height adjusted for age was in 24% of the patients with PKU of Dutch parents and weight adjusted for height in 11% under the 10th centile. Ninety per cent of the patients with PKU of 5 years and older attended primary or secondary school, compared with 95% in the general population. PMID- 2270130 TI - [The significance of body temperature, sedimentation, C-reactive protein, leukocyte count and differential for the diagnosis of infections in an internal medicine emergency department]. AB - The value of body temperature, erythrocyte sedimentation rate (ESR), C-reactive protein, white blood cell count and differentiation for the diagnosis of infections in patients in the first aid department of internal medicine, was investigated. Forty-six infections were observed in 260 patients (prevalence 18%). Patients with fever had a fourfold increased chance to have an infection. In a patient with fever and an increased ESR the chance to have an infection was 91%, with fever and a normal ESR 33%. In the absence of fever the chance to have an infection was 14% if the ESR was increased and 7% if normal. White blood cell count and differentiation, like C-reactive protein in addition to body temperature were of no use for the diagnosis of infections. PMID- 2270131 TI - [A patient with hypersensitive carotid sinus syndrome]. AB - We describe a patient with carotid sinus hypersensitivity that is cardiodepressive as well as vasodepressive. He was treated with AV-sequential pacing after which his complaints were reduced considerably. The various forms of carotid sinus hypersensitivity and their therapeutic consequences are discussed. PMID- 2270132 TI - [The future of the 2d stage of medical education; the final report of the Policy Oriented Study Medical Residencies and the symposium concerning this]. PMID- 2270133 TI - Osmotic effects upon excitability in rat neocortical slices. AB - Acute osmotic disturbances can lead to profound neurological problems, yet there has been little experimentation at a cellular level to assess if neurophysiological changes are induced by altered osmolality. Using extra- and intracellular recording in the rat neocortical slice preparation, we examined pyramidal neurons of layers II-III under changing osmotic conditions. Single cell properties, field potentials, synaptic transmission and epileptiform discharges were studied in control saline (295 mOsm) and compared with corresponding data collected during exposure to osmolalities between 245 and 375 mOsm. Single cell properties (resting membrane potential, cell input resistance, action potential threshold and duration) did not change significantly, but neuronal interactions were considerably influenced by osmotic change within minutes. Hyposmolality increased the amplitude of evoked field potentials and of excitatory postsynaptic potentials recorded intracellularly. Hyperosmolality, induced with mannitol, decreased these parameters. Electrotonic coupling, as gauged by the degree of dye coupling and by cell input resistance, was not influenced by shifts in osmolality. The clinical finding that overhydration promotes seizure onset was examined in slices made epileptogenic in Mg2(+)-free saline. Hyposmolality increased the frequency and decreased the duration of interictal bursts, whereas raising osmolality with mannitol had opposite effects. None of the aforementioned effects occurred when osmolality was increased with a freely permeable substance such as dimethylsulfoxide, nor could they be ascribed to changes in saline Na+ or Ca2+ concentrations. The results are consistent with hyposmotic solutions reducing extracellular space by causing cells to swell. Theoretically, during population discharge, this should both concentrate K+ released extracellularly and possibly increase field (ephaptic) interactions. How lowered osmolality strengthens spontaneous and evoked excitatory synaptic transmission in neocortex is not yet clear. However, it may be an important mechanism underlying the increased seizure susceptibility of patients and experimental animals with lowered plasma osmolality. Conversely, suppression of excitatory postsynaptic potentials by osmotically active substances may be involved in the lowered seizure susceptibility observed clinically. PMID- 2270134 TI - Functional stability of the brain slices of ground squirrels, Citellus undulatus, kept in conditions of prolonged deep periodic hypothermia: electrophysiological criteria. AB - The brain of hibernating animals, controlling the physiological functions during the hibernation cycles, is itself subject to deep cooling during bouts of hibernation. This suggests its high tolerance to deep hypothermia. Effects of prolonged deep cooling were investigated in hippocampal and septal slices, taken from the brains of three groups of animals: hibernating ground squirrels, actively waking ground squirrels, and guinea-pigs. The slices were kept at a low temperature (2-4 degrees C) for various periods of time (from several hours up to six days) and periodically tested in warm (31 degrees C) incubation medium. The hippocampal field potentials (mainly of field CA1), as well as spontaneous activity of single neurons of hippocampus and medial septum were recorded. For comparative purposes mean amplitudes of population spikes and mean frequency of spontaneous neuronal discharge were used. Significant differences between the experimental groups were observed in recovery of functional activity of the slices after their dissection from the brain, as well as after deep cooling. In both cases re-establishment of neuronal activity in ground squirrels occurred more rapidly, than in guinea-pigs. The most dramatic was the difference in maximal time of survival of the slices under conditions of deep cooling. Independently of periodicity of the electrophysiological testing in warm medium, the slices taken from hibernating squirrels retained their activity for seven to nine days, the slices of waking ground squirrel hippocampus survived up to six to seven days, while those of guinea-pis did not recover their functional activity after cooling for more than one to two days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270135 TI - Paradoxical state-dependent excitability of the medial septal neurons in brain slices of ground squirrel, Citellus undulatus. AB - Spontaneous and evoked neuronal activity of the medial septum-diagonal band complex was investigated extracellularly in slices, taken from the brain of the three groups of animals: hibernating ground squirrels, waking ground squirrels, and guinea-pigs. All slices were incubated at 31-32 degrees C. The slices of the ground squirrels' brain were retested after keeping them for 15-36 h in the refrigerator at 2-4 degrees C. In all experimental groups the majority of the medial septum-diagonal band complex neurons had high regular or rhythmic burst spontaneous activity, which in half of the neuronal population persisted in conditions of synaptic blockade. The low-frequency irregular activity of the surrounding structures (lateral septum, caudate, accumbens, medial preoptic area) was completely suppressed in these conditions. The density of the spontaneously active neurons in the slices, as well as the mean frequency of discharges in the medial septum-diagonal band complex of hibernating ground squirrels, was significantly higher than that in waking ground squirrels and guinea-pigs. Stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the medial septum-diagonal band complex units; in many of them the suppression was followed by a burst discharge. The neurons with background rhythmic burst activity always responded by resetting the spontaneous bursts. In total, about 50-60% of the medial septum-diagonal band complex neurons of waking ground squirrels and guinea-pigs responded by post inhibitory bursts to the stimulation of medial forebrain bundle, while in hibernating ground squirrels such responses were observed in nearly all neurons. The threshold values of the stimulating current were significantly lower in the hibernating ground squirrels' group, the mean duration of the initial suppression was shorter, the intraburst density of spikes and/or duration of the bursts was increased. Thus, evaluation of spontaneous and evoked activity on the basis of various criteria revealed surprising similarity between the two groups of active animals, while the activity and excitability of the medial septum-diagonal band complex neurons was approximately doubled in the hibernating animals. This difference between active and hibernating ground squirrels was preserved during retesting after deep and prolonged cooling of the slices. The experiments demonstrate paradoxical stable increase of activity and excitability of the medial septum-diagonal band complex neurons in the hibernating ground squirrels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270136 TI - Coherence of compound field potentials reveals discontinuities in the CA1 subiculum of the hippocampus in freely-moving rats. AB - The ongoing micro-electroencephalogram was recorded with a chronically implanted comb-like array of 16 tungsten semi-microelectrodes 0.2 or 0.25 mm apart, spanning CA1 strata oriens, pyramidale and radiatum and into subiculum, in four behavioral states: walking, standing still, paradoxical and slow wave sleep and under scopolamine. Power, phase and coherence spectra were computed, the latter two for each of the 120 pairs, in frequency bands from 1 to 64 Hz. (1) Coherence is high for all frequencies within the same subfield, e.g. stratum radiatum, but falls with distance. Theta frequency (8 Hz), when prominent and widespread (during "theta states" walking and paradoxical sleep), shows the most widespread synchrony: coherence falls slowly, from 1.0 at 0.2 mm to 0.7 at c. 2 mm longitudinally within stratum radiatum; all other frequencies fall two or three times faster. (2) An abrupt drop in coherence occurs across field borders (CA1 subiculum) and between stratum oriens and radiatum, across a line just under stratum pyramidale, between high coherence regions on each side of the coherence discontinuity. A less extreme drop occurs in stratum radiatum 0.4 mm from the subiculum border, without obvious histological correlate. The discontinuities in coherence are stable through all four behavioral states as well as under scopolamine. (3) Phase profiles diagonally across CA1 and into subiculum show abrupt, local shifts of phase (up to 125) at these same levels. No gradual shift reaching 180 (phase reversal) occurs in the span of loci examined. (4) The theta power peak in theta states is not necessarily due to additional energy in that band; in some conditions it is mainly due to reduced power in other frequencies. Root mean square voltage is generally less in the high theta ("synchronized") than in the non-theta states. Only the theta peak correlates with a peak in coherence. (5) Significant microstructure in the dynamics of neuronal cooperativity distinguishes behavioral states and regions of the hippocampal cortex. PMID- 2270137 TI - Tetanus toxin blocks inhibition of granule cells in the dentate gyrus of the urethane-anaesthetized rat. AB - Field potentials of dentate granule cells in response to stimulation of the perforant path have been studied before and after injecting tetanus toxin (200 mouse LD50; or phosphate-buffered saline in controls) into the hilus of the dentate gyrus of rats under urethane anaesthesia. Within 1 h of toxin injection, the population spike, but not the slope of the excitatory postsynaptic potential, had increased markedly in amplitude and double or treble population spikes appeared in response to perforant path stimulation. Both paired pulse inhibition (15-ms interval between conditioning and test stimuli) and commissural inhibition (10-ms interval) were substantially reduced by the toxin. Neither multiple spikes nor the reduction in inhibition were seen in controls. Apparent inhibition of the excitatory postsynaptic potential, seen with paired stimuli to the perforant path, was not affected by the toxin. At later times after the injections, a progressive increase in the size of the spikes was seen in the controls while in the toxin animals there was often a secondary decrease in size. It is concluded that tetanus toxin can block both feed-back and feed-forward inhibitory components acting on dentate granule cells. The results are discussed with respect to the role of inhibitory processes in the control of epileptogenesis. PMID- 2270138 TI - Localization of neuropeptide precursor-synthesizing neurons in the rat olfactory bulb: a hybridization histochemical study. AB - The distribution of seven kinds of neuropeptide precursor mRNA-containing neurons was investigated in the rat main and accessory olfactory bulbs, where various peptides have previously been identified immunohistochemically, by means of in situ hybridization using [35S]cRNA probes. In the glomerular layer, numerous preprothyrotropin-releasing hormone mRNA-expressing neurons, moderate numbers of preprosomatostatin and preproenkephalin A neurons, and a small number of preprocholecystokinin neurons were detected. In the external plexiform layer, numerous medium sized preprocholecystokinin and preprocorticotropin-releasing hormone neurons, and a small number of beta-preprotachykinin A neurons were observed. In addition, small preprovasoactive intestinal polypeptide and preprothyrotropin-releasing hormone neurons were evenly distributed in the external plexiform layer. Medium to large sized beta-preprotachykinin A neurons formed a thin layer in the mitral cell layer. In the granule cell layer, in addition to numerous small preproenkephalin A neurons, moderate numbers of small beta-preprotachykinin A and preprocorticotropin-releasing hormone neurons, and a small number of preprothyrotropin-releasing hormone neurons, were identified. Large sized preprosomatostatin neurons were located in the deep layer of the granule cell layer. The distribution patterns of these neurons, as a whole, confirmed previous studies based on immunohistochemistry, although peptide precursor mRNA-expressing neurons were far more numerous than those immunoreactive to the respective neuropeptides. Moreover, mRNA-expressing neurons were observed in areas where no immunoreactive neurons had been observed (e.g. preprovasoactive intestinal polypeptide and preprosomatostatin neurons in the mitral cell layer of the assessory olfactory bulb). The distribution patterns were generally similar in the main and accessory olfactory bulbs. PMID- 2270139 TI - Immunoelectron microscopic localization of cell adhesion molecule L1 in developing rat pyramidal tract. AB - The glycoprotein L1 is a cell adhesion molecule that has been proposed to function in the peripheral nervous system in axon fasciculation and onset of myelination. In this report we localize L1 during the development of a major central pathway: the pyramidal tract. The (sub)cellular localization of L1 was determined both by pre-embedding staining on Vibratome sections and by immunogold labelling on ultracryosections in developing rat pyramidal tract at the fifth cervical segment. On arrival at the fifth cervical segment, i.e. at postnatal day 1, growth cones of pioneer fibres did not exhibit L1-immunoreactivity. In the contact zone between pyramidal tract growth cones and glial processes no L1 immunoreactivity was observed. A clear L1-immunoreactivity was noted on small unmyelinated other axons situated in the entrance area of the pyramidal tract growth cones. Also on later arriving, i.e. between postnatal days 2 and 10, small unmyelinated fasciculating pyramidal tract axons L1 were present. It is our impression that L1 is localized in an irregular patchy way on the outer side of the axonal membrane. During the onset of myelination, i.e. between postnatal days 10 and 14, L1 could not be detected on axons ensheathed by oligodendrocytic processes. When myelination is largely completed, i.e. at postnatal day 21, the L1 antigen could be localized within the axoplasma of both unmyelinated and myelinated pyramidal tract axons. Furthermore, L1 could be observed occasionally on small unmyelinated pyramidal tract axons. Whereas compact myelin was always L1 negative, L1 was noted periaxonally between the axolemma and compact myelin and at (para)nodal regions at the contact zone between axolemma and oligodendrocytic processes. From these results it may be deduced that: (1) L1 is involved in fasciculation of outgrowing later arriving pyramidal tract fibres: (2) L1 is not involved in the onset of myelination in this central tract; (3) L1 might play an additional adhesive role in myelinated rat pyramidal tract. PMID- 2270140 TI - Bradykinin-induced release of calcitonin gene-related peptide from capsaicin sensitive nerves in guinea-pig atria: mechanism of action and calcium requirements. AB - The mechanism of neuropeptide secretion induced by bradykinin from capsaicin sensitive afferents was studied in guinea-pig atria. Both the inotropic response induced by bradykinin (0.1 microM) in the electrically driven isolated guinea-pig left atria and the bradykinin (10 microM)-induced release of calcitonin gene related peptide calcitonin gene-related peptide-like immunoreactivity from slices of guinea-pig atria were abolished in vitro by capsaicin pretreatment or in the presence of indomethacin. Bradykinin-induced calcitonin gene-related peptide-like immunoreactive release was unaffected by tetrodotoxin (0.3 microM), the protein kinase C inhibitor, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (30 microM), nefedipine (1 microM) or Ruthenium Red (10 microM). It was significantly reduced by 79% in a Ca2(+)-free medium and by 52% in the presence of 0.1 microM omega conotoxin (fraction GVIA). It is proposed that bradykinin releases calcitonin gene-related peptide from capsaicin-sensitive afferents in guinea-pig atria, via prostanoid generation. This mode of activation of the "efferent" function of capsaicin-sensitive nerves appears to be distinct from those produced by capsaicin or electrical field stimulation as they have been characterized in previous works. In fact, the bradykinin activation of capsaicin-sensitive afferents is not affected by tetrodotoxin and Ruthenium Red, but is partially sensitive to the selective blocker of N-type Ca2(+)-channels, omega-conotoxin. PMID- 2270141 TI - Effects of inhibition of GABA catabolism by aminooxyacetic acid on enkephalinergic neurons--immunocytochemical and ultrastructural study in the enkephalinergic hypothalamoseptal tract of the guinea-pig. AB - The immunocytochemical and ultrastructural features within [Met]enkephalin neurons of the guinea-pig hypothalamoseptal tract were investigated under chronic inhibition of GABAergic catabolism. This was achieved by raising the brain GABA concentration with aminooxyacetic acid which inhibits GABA-transaminase, the enzyme responsible for the catabolism of GABA. Guinea-pigs were injected intraperitoneally with 10 or 20 mg/kg per day aminooxyacetic acid for two, four or eight days and killed 16 h post-dose. Repeated injections of aminooxyacetic acid produced a great increase in immunoreactivity for GABA in nerve endings surrounding enkephalinergic perikarya in the magnocellular dorsal nucleus of the guinea-pig. Extensive immunocytochemical studies stressed the increase and redistribution of the immunoreaction for [Met]enkephalin in the perikarya of the magnocellular dorsal nucleus under such GABAergic activation. Quantitative and statistical analyses showed that administration of aminooxyacetic acid for eight days significantly increased the intensity of labelling within stimulated perikarya (P less than 0.001). A concomitant accumulation of immunopositive large granules in the enkephalinergic boutons of the lateral septum was observed. In the same way, ultrastructural changes in enkephalinergic cell bodies were analysed and reflected disturbances in the biosynthetic and digestive activities of enkephalinergic perikarya. We postulate that chronic inhibition of the GABAergic catabolism leads to modification in the metabolism of enkephalinergic neurons and to an inhibitory action of GABA on the [Met]enkephalin release from nerve endings. This study give morphological support to the complex functional interactions between GABA and opioid peptide transmitter system. PMID- 2270142 TI - Ultraterminal sprouting in innervated and partially denervated adult and aged rat muscle. AB - End plates from the extensor digitorum longus, soleus and diaphragm muscles of adult (10-month-old) and aged (25-month-old) rats were examined to determine whether aging affects the frequency of occurrence of ultraterminal sprouting, a form of terminal sprouting commonly associated with muscle denervation. There was a significant increase in the fraction of end plates exhibiting ultraterminal sprouts in the extensor digitorum longus muscle only; the number increased from 5.5% in 10-month-old animals to 23.0% in 25-month-old animals. To see whether age also influences the sprouting response to denervation, extensor digitorum longus muscles from 10-and 25-month-old animals were partially denervated by severing spinal nerve L5, and end plates were examined 4-7 and 10-14 days following denervation. Denervation induced a more profound increase in the percentage of end plates exhibiting ultraterminal sprouting in the 10- compared with 25-month old animals. However, sprouting remained significantly greater in the 25- compared with the 10-month-old animals. Furthermore, following denervation the average ultraterminal sprout length was significantly greater in the 25- compared with the 10-month-old animals. There was no correlation between the extent of muscle denervation and the percentage of end plates exhibiting ultraterminal sprouts. End plates with ultraterminal sprouts had larger areas and contained fewer nerve terminal branches than end plates without these sprouts. It is suggested that the limited response to partial denervation in the 25-month-old extensor digitorum longus muscles may indicate that the aged extensor digitorum longus has already approached the maximum capacity for sprouting. PMID- 2270143 TI - Opioid-like immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. AB - In this study we sought to establish the distribution, projections and neurochemical coding of opioid immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. Non-cholinergic secretomotor neurons in the submucous ganglia have been shown to be immunoreactive for dynorphin A 1-8, dynorphin A 1 17, dynorphin B and alpha neo-endorphin while cholinergic neurons have been shown to be immunoreactive for dynorphin A 1-8 only. Thus all submucous neurons in the guinea-pig ileum are immunoreactive for prodynorphin-derived peptides. Two major populations of opioid immunoreactive fibres projecting to the submucous ganglia have been established. Firstly, neurons immunoreactive for prodynorphin-derived peptides and vasoactive intestinal peptide project anally from the myenteric plexus to the submucous ganglia. Secondly, a substantial proportion of sympathetic postganglionic fibres immunoreactive for tyrosine hydroxylase, and projecting from the coeliac ganglion to submucous ganglia, have been shown to be immunoreactive for prodynorphin-derived peptides. Other smaller populations of opioid-immunoreactive neurons include fibres immunoreactive for substance P, enkephalin and dynorphin A 1-8 which project from the myenteric plexus to the non ganglionated plexus of the submucosa. These fibres are probably excitatory motor neurons to the muscularis mucosae. The present paper has described several distinct populations of opioid immunoreactive neurons in secretomotor pathways of the guinea-pig ileum. Furthermore we have shown that these enteric or postganglionic sympathetic neurons contain opioid peptides in combination with other neurotransmitter substances. These results should provide a firmer basis on which to plan functional experiments to elucidate the physiological role of opioid peptides in the enteric nervous system. PMID- 2270144 TI - FMRFamide-like immunoreactivity in the brain of the honeybee (Apis mellifera). A light-and electron microscopical study. AB - Peptide-FMRFamide-like immunoreactivity in the brain and suboesophageal ganglion of the honeybee Apis mellifera L. is demonstrated with the peroxidase antiperoxidase technique. Immunoreactivity is found in about 120 perikarya of the brain and in about 30 of the suboesophageal ganglion. These cells are distributed in 13 paired clusters representing neurons of different types including neurosecretory neurons projecting to neurohemal organs. Immunoreactivity of different intensity is found in the non-glomerular neuropil around the mushroom bodies, in the lateral protocerebrum, the central body, the optic tubercles, the lobula and medulla of optic lobe, the ocellar neuropil, in multiglomerular elements of the antennal lobes and in the dorsal deuterocerebrum. In the mushroom bodies, immunoreactivity is located in layers of the lobes and stalks, corresponding to intrinsic fibre bundles of some Kenyon cell types. The somata of these intrinsic cells did not show FMRFamide-like immunoreactivity. Electron microscopy of immunostained somata and nerve fibres was performed employing a pre embedding peroxidase-antiperoxidase technique. Fibres of optic lobes and the non glomerular neuropil contain immunoreactive dense core vesicles (diameter 50-165 nm) accumulated in boutons besides small synaptic vesicles and synaptic membrane specializations. Immunoreactive layers of the mushroom body neuropil were analysed at the ultrastructural level. Axon profiles with dense-core vesicles of a small type (diameter 35-75 nm) show only faint immunoreactive products. Immunoreactivity of intrinsic mushroom body neurons does not appear to be specifically correlated with synaptic organelles. Our results indicate that FMRFamide or related peptides peptides may be neuroactive compounds in different classes of nerve cells in the bee brain. PMID- 2270145 TI - Characterization of glucose-6-phosphate dehydrogenase isozymes from human and pig brain. AB - Homogenates of human and pig brain in 10 mM Tris-HCl, pH 8.0 were centrifuged at 25,400 x g for 1 h. The supernatants were electrophoresed in polyacrylamide gels were stained for glucose-6-phosphate dehydrogenase (EC 1.1.1.49) activity. Five distinct bands were visible. Isozymes corresponding to two of those bands were purified from human and pig brain. The isozymes were electrophoretically homogeneous. The native proteins, Mr, 220,000, dissociated in sodium dodecyl sulphate-polyacrylamide gels into a 57,000 Mr subunit. Therefore, the native isozymes are tetramers. None of the isozymes required additional metal ions for activity. At 1 mM concentration Mg2+ and Ca2+, independently or together, activated the isozymes 1.5-fold. The isozymes were NADP(+)-specific. Kmapp values of the G6PD isozymes were similar for NADP+ (6-8 microM), but different for G6P (56-180 microM). The specific activities of the isozymes varied from 50 to 210 units per mg of protein. All isozymes were inhibited by NADPH. The inhibition was competitive with respect to NADP+ and non-competitive with respect to G6P. NADH did not affect any of the isozymes. ATP inhibited the isozymes competitively with respect to G6P and non-competitively with respect to NADP+. Palmitoyl-CoA dissociated the active tetramers into enzymatically inactive dimeric forms. This treatment also abolished the 6-phosphogluconate activity of the isozyme II from both sources. High performance liquid chromatography peptide maps of the tryptic digest and amino acid analyses of the isozymes showed extensive homologies between the corresponding isozymes from the two species. Interestingly, only the isozyme II in human and pig brain was active with 6-phosphogluconate as a substrate (Kmapp = 864 and 279 microM). The specific activities of the isozyme II with 6-phosphogluconate (14 and 48 unit per mg of protein for human and pig brain isozyme II, respectively) was four times less than those with G6P. It is therefore suggested that isozyme II is a bifunctional enzyme. PMID- 2270146 TI - Crack-induced enteric ischemia. AB - Rare instances of intestinal ischemia subsequent to cocaine use have been reported. Crack abuse, linked to gastroduodenal ulcer perforation, has not been associated with mesenteric infarction until this case report. PMID- 2270147 TI - Noninvasive diagnosis of deep vein thrombosis. AB - Deep vein thrombosis is a serious medical problem that may lead to pulmonary embolus. The authors discuss the noninvasive diagnosis of deep vein thrombosis using venous occlusion plethysmography and ultrasonic duplex scanning. PMID- 2270148 TI - Antisense DNA-analogs. Inhibition of human immunodeficiency virus. PMID- 2270149 TI - Mandatory Medicare assignment. PMID- 2270150 TI - Liability in costly AIDS cases expands rapidly as attorneys target physicians and hospitals. PMID- 2270151 TI - Maternal mortality. PMID- 2270152 TI - Professional review and regulations. AB - New federal and state legislation will subject physicians to increasing scrutiny in the 1990s. This article highlights these new laws and explores physician concerns about them. PMID- 2270153 TI - Professional Medical Conduct Reform Act. AB - A new law significantly increases the regulation of New Jersey physicians and heightens the State Board of Medical Examiners scrutiny of potentially impaired and incompetent physicians. The law is a comprehensive expansion of New Jersey's physician peer review. PMID- 2270154 TI - Maternal deaths in New Jersey: 1988. AB - Physicians reported 56 maternal deaths in New Jersey in 1988. AIDS, adult respiratory distress syndrome, and trauma were dominant causes of maternal demise. There continues to be value in reviewing maternal deaths. The authors detail a model protocol. PMID- 2270155 TI - Needle suspension procedures for urinary stress incontinence: a review and historical perspective. AB - Armand J. Pereyra introduced a new approach in the treatment of female urinary stress incontinence which did not require abdominal retropubic dissection. This operation and subsequent modifications by Pereyra serve as the foundation for various needle suspension procedures. The reported cure rates for the Modified Pereyra Procedure and its variations have exceeded 85 per cent in several studies. There has been some suggestion of an increased late failure rate in the Modified Pereyra Procedure compared to abdominal retroubic urethropexy. Additional long-term studies are needed to answer this important question utilizing preoperative and postoperative urodynamic evaluation. Karram and Bhatia in their review of transvaginal needle bladder neck suspension procedures cited three studies which accomplished this in a total of 60 patients. It seems the popularity of needle suspension procedures continues to grow. Increasingly, needle suspension procedures have been used in the outpatient treatment of urinary stress incontinence. A continuing tribute to the operative contributions of Armand J. Pereyra in the treatment of urinary stress incontinence. PMID- 2270156 TI - The county coroner: advancing the image. PMID- 2270157 TI - OSMA: changing directions in the '90s. PMID- 2270158 TI - Matters of priority. PMID- 2270159 TI - Changing indications for cataract surgery: 1974 to 1988. AB - To examine changes in indications for cataract surgery which have contributed to the increasing rate of cataract extractions, we compared preoperative characteristics of 265 patients who had undergone surgery in 1988 with a similar number who had undergone surgery by the same four ophthalmologists in 1974 and 1982. Between 1974 and 1988 the number of extractions performed annually by two high-referral hospital-based surgeons rose by 68%. Over 90% of these procedures in 1974 were intracapsular extractions; in 1988, 90% were extracapsular extractions with intraocular lenses. In 1988, preoperative visual acuity was better in both the study eyes and the fellow eyes, the proportion of those with acuities better than 20/60 having risen from 10% to 21%, and from 49% to 67%, respectively. The proportion of patients waiting more than 2 years for surgery on the second eye doubled between 1974 and 1988. These changes, already evident by 1982 for the hospital-based surgeons, became characteristic of the community based surgeons' practices as well between 1982 and 1988. PMID- 2270160 TI - Lower eyelid retraction: a minimal incision surgical approach to retractor lysis. AB - Lower eyelid retraction associated with prior blepharoplasty, trauma, or other conditions is a challenging problem for the ophthalmic surgeon. We describe a procedure involving tightening the lower eyelid and supraplacing the lateral canthus in combination with in-glove lysis of the lower eyelid retractors and scar tissue. This is accomplished through a small lateral incision. To date, we have treated over 200 eyelids using this technique with excellent results. We recommend this technique for the treatment of mild to moderate degrees of lower eyelid retraction. PMID- 2270161 TI - The bovine eye as a model for the novice cataract surgeon. AB - A simple method for preparing the bovine eye as an in vitro model for training cataract surgeons is described and illustrated. This model allows basic skills to be gained in a graded fashion, using readily available materials. Also, more advanced surgical techniques can be refined by using this model. Manipulation of the model enables mimicking of real-life surgical challenges. Use of bovine eyes may represent, in bioethical terms, efficient use of available biological materials. PMID- 2270162 TI - Techniques for the preservation of enucleated animal eyes in surgical training. AB - The main problem with using enucleated animal eyes in surgical training is that they remain fresh for such a short time. We describe a simple technique to preserve them by replacing the aqueous humor and part of the vitreous with another substance. We used 18 eyes of nine dogs (nine for the study and nine as controls), and three substances (2% methylcellulose, silicone oil, and gelatin). The methylcellulose group had the best results (including long-lasting mydriasis), preserving the eyes in which it was used in optimal surgical condition for up to 8 days, twice as long as the eyes in the control group (P less than .005). PMID- 2270163 TI - A method for performing full-thickness, orthotopic, penetrating keratoplasty in the mouse. AB - In an attempt to overcome the lack of well characterized, inbred, and congenic strains, as well as a paucity of immunological reagents, in rabbit and rat models, we have developed a procedure for performing full-thickness, penetrating keratoplasty in the mouse. One hundred percent of isografts (BALB/c onto BALB/c) were successful, while 83.3% of allografts (C3H onto BALB/c) failed. The use of a mouse model to study corneal graft failure will allow a critical evaluation of the role of a variety of immunological mediators in causing graft failure. PMID- 2270164 TI - Glaucoma triple procedures: efficacy of intraocular pressure control and visual outcome. AB - Sixty-three glaucoma triple surgeries [combined trabeculectomy, extracapsular cataract extraction (ECCE), and posterior-chamber intraocular lens (PC-IOL) implantation] were reviewed. Intraocular pressure (IOP) was controlled satisfactorily in all cases; 25% required additional glaucoma therapy but fewer glaucoma medications. Eighty-six percent achieved 6/12 or better visual acuity. Postoperative IOP and visual acuity results were similar to those achieved by trabeculectomy or ECCE/PC-IOL, respectively. Cumulative years of preoperative glaucoma therapy had an adverse effect on postoperative IOP control. PMID- 2270165 TI - Cyclocryotherapy in selected cases of congenital glaucoma. AB - We investigated the efficacy of cyclocryotherapy, a procedure which destroys the ciliary epithelium, thereby decreasing the production of aqueous humor, by retrospectively studying 109 eyes with advanced primary congenital glaucoma that had undergone the procedure. The eyes were divided into two groups: group I comprised 75 eyes (69%) that had undergone conventional surgical procedures for congenital glaucoma prior to cyclocryotherapy; group II, 34 eyes (31%) that had not undergone any such previous procedures. All eyes were followed for at least 12 months after the last cyclocryotherapy. With "success" defined as "having an IOP greater than or equal to 8 mmHg, greater than or equal to 19 mmHg with or without medication," the success rate in all eyes was 30%, with no significant difference between the success rates in groups I and II (P greater than .05). Chronic hypotony (IOP less than 8 mmHg) was found in seven eyes (6%). Six eyes (6%) developed cataract during the course of treatment with cyclocryotherapy. Cyclocryotherapy appears to be a reasonable addition to the treatment of eyes with advanced, uncontrolled, primary congenital glaucoma. PMID- 2270166 TI - Pressure-curve variations after trabeculectomy for chronic primary open-angle glaucoma. AB - We report the results of a 5-year study of the influence of trabeculectomy on the maximum intraocular pressure (IOP) and the amplitude of its diurnal oscillation in 26 eyes (14 patients) with open-angle glaucoma. Pressure-curves were recorded before surgery and at 1 year and 5 years after surgery. The latter two pressure curves demonstrated that trabeculectomy significantly reduced both the maximum IOP and the amplitude of the oscillations below preoperative values. PMID- 2270167 TI - Mycobacterium chelonei keratopathy with visual rehabilitation by a triple procedure. AB - We report a chronic keratouveitis following an eye injury, the etiology of which remained obscure despite repeated corneal scrapings and cultures. Eventually, the diagnosis was established by culturing Mycobacterium chelonei from a corneal biopsy specimen. Topical amikacin resolved active inflammation, but dense corneal scarring and a cataract remained. Visual rehabilitation was achieved through a combined penetrating keratoplasty, extracapsular cataract extraction, and intraocular lens implantation. This case illustrates that there should be a high index of suspicion of atypical mycobacteria when faced with any unusual keratitis, particularly following penetrating injuries and corneal grafts. PMID- 2270168 TI - Aminocaproic acid prophylaxis in traumatic hyphema. AB - Oral aminocaproic acid has been shown to be effective in clot stabilization and in the reduction of secondary bleeding rates in cases of traumatic hyphema. In a retrospective study of 105 patients treated during a 1-year period, we found the incidence of rebleeding in patients with traumatic hyphema who received aminocaproic acid prophylaxis was 2%; the incidence in those who did not was 25%. PMID- 2270169 TI - Keratoscopy through the slit lamp. PMID- 2270170 TI - Molteno rip-cord related suture hypopyon. PMID- 2270171 TI - [Clinical use of transesophageal echocardiography]. AB - Transoesophageal echocardiography (TE) presents a new window in echocardiography. Experience obtained in the first 70 TE studies performed in 66 patients is reported. The patients' age ranged between 15 and 75 years, there were 36 females and 30 males. Sixty studies were done in awake patients and 10 studies in anesthetized or intubated patients. TE indications included suspected mitral prosthetic valve dysfunction: 20, tumor or thrombus: 11, search for source of embolism: 10, infective endocarditis: 5, congenital heart disease: 8, intraoperative decision-making: 7, acute postoperative hypotension: 3, suspected aortic dissection: 3 and others. There was no unsuccessful intubation or complication. The most important results: the differentiation of left atrial tumor and thrombus by the presence or absence of spontaneous echocontrast, the role of TE in the intraoperative and early postoperative decision making and the diagnosis in rare clinical situations (multiplex myxoma; tricuspid prosthetic valvular regurgitation caused by pacemaker electrode dislocation). It is concluded that TE is a unique diagnostic technique which provides invaluable clinical informations and facilitates therapeutic decision making. It is a safe procedure both in awake and anesthetized patients therefore in certain indications it should supplement standard echocardiographic technique in routine clinical practice. PMID- 2270172 TI - [Two-dimensional ultrasonic examination of the fetal heart]. AB - The methodology of the two-dimensional fetal echocardiography is described by the basic of the accepted international nomenclature. By their opinion it is necessary that on the 18-20th weeks of gestation the high risk pregnancies in aspect congenital heart disease examined by the well-trained specialists. The indication of fetal echocardiography are listed, too. PMID- 2270173 TI - [Clinical course and prognosis of pleuro-pulmonary metastases in patients after surgery for breast cancer]. AB - The data of 63 female patients suffering from pulmonary and/or pleural metastases of breast cancer are recorded. The patients received chemotherapy, according to the CMF (Cyclosphosphamide-Methotrexate-Fluorouracil) scheme, and in case of appropriate indication, a hormone-therapy as well. The mean survival time of the deceased was 22 months whereas the mean follow-up time of those still living is 61 months. These results are better, than those of the literature, mainly if they are compared to the data of patients with inoperable primary lung cancer. PMID- 2270174 TI - [The question of euthanasia]. PMID- 2270175 TI - Bilateral hip and bilateral knee arthroplasties in a patient with ochronotic arthropathy. AB - Alkaptonuria is a rare, autosomal-recessive, inborn, metabolic disease that causes ochronotic arthropathy leading to disabling arthritis. Few reports of arthroplasty in patients with this disease have been published, and none documents four total joint replacements in the same patient. This case report describes the history and findings in a 70-year-old man who underwent bilateral hip and knee total joint arthroplasties with significant improvement in pain and exercise tolerance. The metabolic and clinical aspects of alkaptonuria are also discussed. PMID- 2270176 TI - Team physician #9. The role and responsibilities of the competition physician. AB - The rapid growth of participation in contact sports has been accompanied by an increasing need for sporting event coverage by qualified physicians. The competition physician must not only be capable in contemporary emergency and sports medicine, but must also have organizational skills to coordinate satisfactory medical and ancillary backup. This monograph outlines a comprehensive plan for efficient preparation and execution of on-site sports injury assessment and care. With knowledge, organization, and preparation, competition coverage can be a satisfying component of a sports medicine practice. PMID- 2270177 TI - Tips of the trade #30. Constructing a bracket for fixation of supracondylar fractures in children. AB - Displaced supracondylar fractures in children are best treated with anatomic reduction and percutaneous fixation. Flynn et al first described the pediatric application of a simple holding bracket to facilitate reduction and percutaneous pinning of supracondylar fractures. A similar bracket can be easily constructed with connecting rods and clamps from a Hoffman or an AO external fixator tray. PMID- 2270178 TI - Current concepts in anterior cruciate ligament rehabilitation. AB - Eight years of experience in performing only bone-patellar tendon-bone autograft reconstructions of the anterior cruciate ligament (ACL) are presented, with an emphasis on an accelerated post-operative rehabilitation protocol. Past patient non-compliance to previously established protocols still yielded very acceptable results that demanded further investigation. Gradually we developed a three-phase rehabilitation plan that is implemented after surgical correction of ACL deficiencies. The first phase (zero to two weeks) focuses primarily on wound healing, full extension, control of swelling, and leg control. The second phase (two to five weeks) involves increasing flexion, developing a functional gait, and resuming activities of daily living. The third phase (greater than 5 weeks) identifies a safe return to competitive athletics. This protocol evolved with close observation of approximately 1,000 reconstructions and has been used on the last 650 patients since January 1987. A decreased postoperative morbidity was noted without a compromised clinical stability. PMID- 2270179 TI - Great toe sesamoid injuries in the athlete. AB - Rare, but potentially debilitating, injuries in the athlete may originate from trauma to the sesamoid bones of the great toe. Controlled studies comparing conservative versus surgical treatment outcomes are lacking owing to the limited number of suspected and proven cases of sesamoid stress fracture or sesamoiditis, a nondescript, painful condition involving the sesamoid. Thus, familiarity with the anatomy and congenital variations of the sesamoid is necessary to identify possible pathology in this area. Existing studies of surgical and nonsurgical treatment of athletes with great toe sesamoid injuries are reviewed. PMID- 2270180 TI - Magnetic resonance imaging of pathologic conditions of the Achilles tendon. AB - The advent of magnetic resonance imaging (MRI) has improved imaging of the Achilles tendon. Various pathologic conditions of the Achilles tendon and their MRI characteristics are described. The superior resolution of the tendon provided by MRI can aid in the diagnosis of Achilles tendon disorders, which include complete or partial rupture of the tendon as well as postoperative assessment of tendinous healing, tendinitis and tenosynovitis, and various tumors of the Achilles tendon. PMID- 2270181 TI - Accurate reduction and splinting of the common boxer's fracture. AB - A simple and efficient method of achieving and maintaining reduction of a boxer's fracture (neck of the fifth metacarpal) is described. This method can be implemented during drying of the plaster splint, and adequate roentgenograms can be taken without the presence of redundant plaster over the fracture site found with the traditional ulnar gutter splint. PMID- 2270182 TI - A complication of interference screw fixation in anterior cruciate ligament reconstruction. AB - Bone-tendon autografts using patellar tendon are rapidly becoming the autogenous grafts of choice for anterior cruciate ligament reconstruction. Patellar tendon is the strongest type of available autogenous tissue, and it is easily adaptable to arthroscopically assisted techniques. Secure immediate fixation is critical for the success of this procedure. The Kurosaka screw has emerged as one of the most reliable graft fixation methods. Although we have enjoyed much success with the Kurosaka screw, the following case represents the first report of failure with this fixation technique. PMID- 2270183 TI - Observations on the microstructure of response conflict. AB - Three experiments are detailed which indicate the usefulness of the frequency of double responses (DRs) as an indicant of response conflict, in addition to the usual RT measures. DRs are responses on which an initial (often partial) error response is made that is rapidly amended to a correct response. Such responses occur most frequently in stimulus conditions where response conflict is expected by theory to be present and is indicated by changes in RT. Partial activation of competing responses has been demonstrated before using physiological measures (Coles, Gratton, Bashore, C. W. Eriksen, & Donchin, 1985; C. W. Eriksen, Coles, Morris, & O'Hara, 1985) when both responses could physically be made at the same time. DRs seem to be an equivalent type of movement when the subject cannot physically make but one movement at a time. The usefulness of this index of response conflict lies in its ease of implementation. PMID- 2270184 TI - Perceptual and response interactions in semantic priming. AB - In two experiments, subjects made pairs of lexical decisions verbally. In Experiment 1, masked stimuli appeared concurrently to the left and right of fixation; in Experiment 2, nonmasked stimuli appeared sequentially at fixation. The left-hand letter strings were judged more accurately in in Experiment 1, and the second letter strings were judged more accurately in Experiment 2. Each string in the pair could be either a word (e.g., fork) or a nonword anagram (e.g., frok). Consequently, the two strings in the pair could be related (e.g., fork-spoon, frok-spoon, etc.) or unrelated (e.g., fork-door, frok-door, etc.), independently of whether neither, either, or both strings were words. Semantically related stimuli induced consistent biases to respond "word," as noted in other studies. These biases were typically stronger for the event reported second. Minimal evidence was found for perceptual priming effects. The asymmetrical effects were consistent with spreading-activation-type mechanisms, but other considerations support a multiple-process view. PMID- 2270185 TI - Identity imposition and its role in a stereokinetic effect. AB - Lines of constant curvature, a circle or a straight line, have no distinguishable parts. Yet they are perceived as if they did. When they move and intersect, they are perceived to slide across each other as if one of them had parts that can be seen to move in relation to the other line. With no such parts present in stimulation, they are products of perception. It was found that a third line of constant curvature, the helix, is also seen to slide when two helixes intersect and are in motion. Another manifestation of perceived identical parts is that rotating circles and similar shapes are perceived not to rotate even when cues for rotation are present. Furthermore, changes between merely perceived identical parts can result in apparent depth. Evidence is presented that such depth, known as the stereokinetic effect, results from kinetic depth-effects that are based on perceived identical parts instead of on actually identical parts, and that depth is seen when the intervals between such perceived parts change length and orientation simultaneously. PMID- 2270186 TI - Effects of background symmetry on same-different pattern matching: a compromise criteria account. AB - Two experiments are reported, which were designed to test predictions of an account of same-different matching that assumes that bilaterally symmetric backgrounds provide extraneous evidence toward same, whereas asymmetric backgrounds provide evidence toward different. When all backgrounds within a block of trials are of the same type, appropriate adjustments of response criteria can be made to accommodate the irrelevant evidence and thus maintain acceptable levels of accuracy. However, when backgrounds of different types are mixed randomly, compromise criteria are adopted. This compromise-criteria account predicts distinctive interaction patterns for reaction times when blocked versus mixed presentations of various background types are compared. The predicted interactions were obtained for asymmetric- and no-noise backgrounds in Experiment 1 and for symmetric-, asymmetric-, and no-noise backgrounds in Experiment 2. The findings support the general view that extraneous display attributes are weighted into the evidence for same and different, with criteria settings used that minimize errors under the noisiest conditions. PMID- 2270187 TI - Pervasiveness and magnitude of context effects: evidence for the relativity of absolute magnitude estimation. AB - To test the assertion that absolute magnitude estimation serves to minimize context effects, two experiments were conducted in which area stimuli were judged under differing conditions. In Experiment 1, four groups of subjects made magnitude estimations of triangles ranging in area from 1.5 to 3,072 cm2. No standard or modulus was used, and instructions were similar to those used in absolute magnitude estimation experiments. Each group first judged a different subrange of the stimuli (1.5-24; 48-768; 6-96; or 192-3,072 cm2) before making judgments of the remaining stimuli. In Experiment 2, two groups of subjects made magnitude estimations of triangles ranging in area from 1.5 to 12,288 cm2, with each group first judging a different subrange of stimuli (1.5-24 cm2 or 768 12,288 cm2). The design and instructions were virtually identical to those used in absolute magnitude estimation experiments. Our results indicate that the wording of the instructions is not crucial and that judgments are influenced in two ways that are not predicted by proponents of absolute magnitude estimation. First, the power functions fit to the initially presented subranges (e.g., 1.5-24 cm2), which were judged without contextual effects produced by previously presented stimuli, were inconsistent with one another. Second, judgments of the remaining stimuli were influenced by the subrange of stimuli judged initially. The prevalence of context effects in both experiments, in spite of instructional differences, suggests that although one should avoid using a standard and modulus, there is little else to be gained by adopting the absolute magnitude estimation procedure. PMID- 2270188 TI - Young infants' perception of liquid coarticulatory influences on following stop consonants. AB - Phonetic segments are coarticulated in speech. Accordingly, the articulatory and acoustic properties of the speech signal during the time frame traditionally identified with a given phoneme are highly context-sensitive. For example, due to carryover coarticulation, the front tongue-tip position for /1/ results in more fronted tongue-body contact for a /g/ preceded by /1/ than for a /g/ preceded by /r/. Perception by mature listeners shows a complementary sensitivity--when a synthetic /da/-/ga/ continuum is preceded by either /al/ or /ar/, adults hear more /g/s following /l/ rather than /r/. That is, some of the fronting information in the temporal domain of the stop is perceptually attributed to /l/ (Mann, 1980). We replicated this finding and extended it to a signal-detection test of discrimination with adults, using triads of disyllables. Three equidistant items from a /da/-/ga/ continuum were used preceded by /al/ and /ar/. In the identification test, adults had identified item ga5 as "ga,' and dal as "da,' following both /al/ and /ar/, whereas they identified the crucial item d/ga3 predominantly as "ga' after /al/ but as "da' after /ar/. In the discrimination test, they discriminated d/ga3 from da1 preceded by /al/ but not /ar/; compatibly, they discriminated d/ga3 readily from ga5 preceded by /ar/ but poorly preceded by /al/. We obtained similar results with 4-month-old infants. Following habituation to either ald/ga3 or ard/ga3, infants heard either the corresponding ga5 or da1 disyllable. As predicted, the infants discriminated d/ga3 from da1 following /al/ but not /ar/; conversely, they discriminated d/ga3 from ga5 following /ar/ but not /al/. The results suggest that prelinguistic infants disentangle consonant-consonant coarticulatory influences in speech in an adult-like fashion. PMID- 2270189 TI - Mixed-method mixed-modality psychophysical scaling. AB - Four experiments are reported in which the direct psychophysical scaling methods of magnitude estimation, category judgment, and cross-modality matching were mixed in the same series of trials, both with a single stimulus modality and in a mixed-modality situation. The mixed-method scaling situation gave results consistent with those obtained when methods are used alone, and it has several advantages. Interactions between the methods were consistent with the idea that judgments made under all three are mediated by a primitive process of categorization that is influenced by heuristics used to achieve a single category identity for each stimulus. PMID- 2270190 TI - Detection and discrimination of coherent motion. AB - When viewing a pair of bars defined by the difference of spatial Gaussian functions (DOGs), human observers can discriminate accurately the relative movements of the bars, even when they differ in spatial frequency. On each trial, observers viewed two brief presentation intervals in which a pair of vertically oriented DOGs moved randomly back and forth within a restricted range. During one interval, both bars moved in the same horizontal direction and by the same magnitude (correlated movements); in the other interval, their movements were uncorrelated. When discrimination accuracy is related to the simultaneous detection of two independent movements, it was found that, if observers can detect the movements of spatially separated bars, they can tell whether their relative movements are correlated. Performance remained remarkably accurate even when the two bars differed in spatial frequency by more than two octaves or were presented separately to the two eyes. Apparently, the accurate discrimination of coherent motion involves an efficient spatial integration of optical motion information over multiple spatial locations and multiple spatial scales. PMID- 2270191 TI - Temporal perturbations of binocular rivalry. AB - Successive durations of binocular rivalry are sequentially independent, random variables. To explore the underlying control process, we perturbed the cycle during a 30-sec viewing period by immediately forcing an eye to return to dominance whenever it became suppressed. During this period of forced dominance, that eye's individual dominance durations were unusually brief, but immediately following the period of forced dominance that eye's suppression durations were unusually long. However, no long-term change in the sequential pattern of rivalry occurred, and the stochastic independence of successive durations was maintained during and following the period of forced dominance. The same pattern of results was obtained with even longer periods of forced dominance. These results are consistent with the existence of a short-term adaptation, or fatigue, process responsible for transitions from dominance to suppression. PMID- 2270192 TI - Electrophysiological evidence for parallel and serial processing during visual search. AB - Event-related potentials were recorded from young adults during a visual search task in order to evaluate parallel and serial models of visual processing in the context of Treisman's feature integration theory. Parallel and serial search strategies were produced by the use of feature-present and feature-absent targets, respectively. In the feature-absent condition, the slopes of the functions relating reaction time and latency of the P3 component to set size were essentially identical, indicating that the longer reaction times observed for larger set sizes can be accounted for solely by changes in stimulus identification and classification time, rather than changes in post-perceptual processing stages. In addition, the amplitude of the P3 wave on target-present trials in this condition increased with set size and was greater when the preceding trial contained a target, whereas P3 activity was minimal on target absent trials. These effects are consistent with the serial self-terminating search model and appear to contradict parallel processing accounts of attention demanding visual search performance, at least for a subset of search paradigms. Differences in ERP scalp distributions further suggested that different physiological processes are utilized for the detection of feature presence and absence. PMID- 2270193 TI - [Tuberculosis: future perspectives in industrialized and in developing countries]. PMID- 2270194 TI - [Tuberculosis in Scandinavia--Finland families' black sheep]. AB - The incidence of tuberculosis in the Nordic countries is one of the lowest in the world: Denmark 5.1, Iceland 6.4, Norway 6.9 and Sweden 6.5; whereas in Finland it is around the mean for Europe, 28.9 per 100,000 (1988). The immigrants are the risk group because they usually come from countries with a high prevalence. The BCG-vaccination at birth is still used in Finland. Other Nordic countries vaccinate mainly the risk groups. Revaccination is no longer indicated. After the discontinuation of the BCG at birth in 1975 the sensitivity to environmental mycobacteria has increased in Sweden. The screening programmes have been phased out but there is reason to take tuberculosis into account at pre-employment examinations, and to perform meticulous contract tracing of the smear-positives. Effective short course chemotherapy is given in all the countries. The Nordic countries must continue to keep accurate tuberculosis registers, to maintain the high diagnostic level and successfully apply the latest high technology and know how for the eradication of tuberculosis which, however, will persist into the next generation. PMID- 2270195 TI - [Tuberculosis incidence in Iceland]. AB - The incidence of tuberculosis in Iceland is still declining and in the last three year period was 6.1 per 100,000 inhabitants. Several of those infected had recently visited countries with a high incidence of tuberculosis. PMID- 2270196 TI - Resurgence of tuberculosis on the coattails of the AIDS epidemic. PMID- 2270197 TI - [Home treatment with parenteral antibiotics--a treatment alternative for Scandinavian patients?]. AB - Home intravenous antibiotic therapy (HIVAT) is increasingly employed for the treatment of chronic infections in the USA. HIVAT has been shown to be safe and effective, and is clearly cost effective for patients, hospitals and society when compared with equivalent therapy rendered in a hospital. Health care, as currently delivered in the Nordic countries, should be well suited for the adaptation of HIVAT. It is anticipated that HIVAT could bring about a substantial reduction in the expenses associated with antibiotic treatment in the Nordic countries. PMID- 2270198 TI - [Screening of donor blood for anti-HIV. Experiences from blood donor screening 1986-1988]. AB - During the period 1986--1988, approximately 1,200,000 portions of blood were anti HIV screened in Denmark. A total of 19 donors were found to be anti-HIV positive and no increase in the frequency of anti-HIV blood donors has been observed during this period. At a subsequent interview, nine out of these 19 donors (47%) were shown to have risk factors for HIV infection. During the same period, a total of 12 cases of transfusion-associated HIV infection were found at follow-up control of recipients of blood from previous donations from donors demonstrated to be positive after 1986. Four of the cases were demonstrated to be positive by blood donor screening and eight in other ways. Finally, five cases of transfusion associated HIV infection in recipients have been reported where no positive donor could be identified. One case of HIV infection could be attributed to transfusion with screened anti-HIV negative blood. On the basis of information from blood donor screening, it is concluded that the risk that a screened anti-HIV negative blood portion in Denmark can transmit HIV infection is less than one per 400,000. PMID- 2270199 TI - [Interactions between cytostatic agents and other drugs]. AB - Drug interactions are increasingly common, since the clinical practice is getting more complex with the flood of new drugs. Simultaneously, the increased life expectancy of the population increases the number of individuals likely to receive multiple prescriptions. Cytotoxic drugs generally have a narrow therapeutic index, and are delivered at doses close to toxic levels. Consequently, a slight increase of the biological activity caused by an interaction with other concomitantly administered drugs could be deleterious for the patient. Interactions between drugs can sometimes also be used in a positive way, i.e. to increase the therapeutic ratio. Interactions between different cancer treatment modalities have attracted considerable interest. However, much less interest has been denoted to interactions between anticancer drugs and other pharmaceuticals. The purpose of this review is to summarize data about the interactions between anticancer drugs and other clinically used drugs with regard to effects on tumor and toxicity. PMID- 2270200 TI - [Research in developing countries: will leprosy vaccine be produced in Nepal?]. AB - Clinical, bacteriological and immunological research into leprosy is pursued at the Anandaban Leprosy Hospital on the outskirts of Kathmandu in Nepal with support from the World Health Organization and research laboratories in inter alia Holland and Australia. The bacteriological part consists of research into cultivation procedures on mice for diagnosis of Mycobacterium Leprae resistance to dapsone and rifampicin. Serological studies have also yielded M. Leprae specific antibodies, a method which, it is hoped, will be further developed as an aid to diagnosis and follow-up of treatment. Research concerning a leprosy vaccine is also in progress. PMID- 2270201 TI - [The medical concept of causality]. PMID- 2270202 TI - [Treatment of meningitis in Denmark]. PMID- 2270203 TI - [Prehospital treatment in Copenhagen]. AB - Medical students may now do their electives with the doctor manned ambulances in Copenhagen in order to observe acute pre-hospital treatment. The author stresses the importance of seeing the patients in their own social setting with their acute symptoms and there being able to observe the reactions of patient and kin alike as well as learning how to react to peoples' grief. PMID- 2270204 TI - [Research in theory and practice. Regional course in North Jutland]. PMID- 2270205 TI - [Reconstruction of anterior teeth using composite materials]. AB - Composite resin has an inorganic period amidst an organic matrix. The following descriptions of the components of the organic phase, and the different types of inorganic phases, highlight the multiple theoretic possibilities for reconstruction with the types of materials selected. The period of composite is thus not unique nor invariable during a certain time. Initially, with a preliminary etching and collage, these different composites produce materials of solid reconstitutions. PMID- 2270206 TI - A map of natural fluoride in drinking water in Sudan. AB - Fluoride is present in most natural elements, in particular in water, with the level being different depending on the region. The level theoretically ideal at 1 mmg/l, is in regions of the Sudan, either surpassed or not attained. After looking at the geography of the country, the levels of fluoride in water was established for each region. It would be ideal, in the case where fluoride was absent, to use an artificial fluoridation scheme. PMID- 2270207 TI - [Hepatitis B at the Dakar Dental School]. AB - Numerous studies have revealed the personal risk of contamination of the virus hepatitis B (HBV). Dental surgeons are chiefly concerned about their almost continual contact, professionally, with blood and saliva. The authors report the results of a study done at the Dental Institute of Dakar. This study revealed the importance of AgHBS and its different functions during the period of observation. A particular point of this study is to emphasis subjects of serology, notably AgHBS+ Anti HBC-, which produce an alternative virus. This study, which is being followed up, has already enabled the commencement of disease prevention programmes of hepatitis through the vaccination of some students: protecting both the dental surgeons and their patients. PMID- 2270208 TI - Dental and skeletal changes in juvenile hypothyroidism following treatment: case report. AB - A case of juvenile hypothyroidism is presented showing evidence of delayed shedding of deciduous teeth, root development, eruption of permanent teeth as well as retarded skeletal growth. Changes in dental and skeletal ages were of varying degrees following two years of treatment with L-thyroxine. PMID- 2270209 TI - Prevalence of bimaxillary protrusion in a Nigerian population. AB - Literally, bimaxillary protrusion means the protrusion of the two maxillae. This concept masks the real orthodontic problem of dual incisor proclination (DIP). In an attempt to clarify the identification of DIP a study has been made of biological norms for incisor proclination. In the Nigerian population, DIP is defined as occurring when the intercisal angle is of or less than 108 degrees. On this basis the prevalence of DIP was recorded as 20 per cent. Approximatively three-quarters of persons with DIP had a skeletal 1 antero-posterior jaw relationship. PMID- 2270210 TI - [Descriptive and technical study of dental inlays in pre-Colombian Mexico]. AB - The authors presents, in this paper, a study on dental inlays among Mexican pre Colombians. To begin with, from the study sources, systematization, classification and some characteristics were extracted, being the best method for later being able to study the descriptive and technical aspects of these inlays while insisting on the quality of the cement used. PMID- 2270211 TI - [Dens in dente. Apropos of a clinical case]. AB - Dens in dente was described by authors as tooth characterized by a non limited apex. This tooth was localized into right upper lateral incisor and was diagnosed for an eight old child consulting for a canine incisor region tumefaction. This anomaly was only diagnosed by radiography showing radio-opaque structures in the pulpar chamber. PMID- 2270212 TI - Primary oral health care. The Tanzanian experience. AB - Four years have elapsed since the introduction of the preventive oral health care approach by the Ministry of Health (1982-1985). A review of the new policy after four years of its implementation indicate that progress has been made in the utilization of non dental personnel in preventive oral health care. Current strategies are sound and some areas have been identified for more intensive activity in the future. The important area is the role of dental personnel in pursuing the concept of primary health care in the regions and districts. This assessment is of importance because total eradication of oral diseases by prevention is so far impossible and would need the whole national budget of Tanzania. PMID- 2270213 TI - [Epidemiological survey of oral status of 7, 12 and 15-year old Cape Verde school children]. AB - A representative sample of 614 schoolchildren of Cape Verde Islands, 7, 12 and 15 years old, was randomly selected. The dental caries prevalence was determined in each age group using the dmft and DMFT indices. The mean DMFT index increased from 2.38 at age 7 to 4.5 at age 15 years. The percentage of children with caries free permanent teeth decreased from 74.5% to 10.4% between 7 and 15 years of age. PMID- 2270214 TI - Radiation doses to the Gonadal area in dental radiography. AB - The authors study the dose of radiation received in the Gonadal areas during intra-oral or panoramic radiography performed at the college of Dentistry in Riyadh, Saudi Arabia. The results show a negligible generic risk. PMID- 2270215 TI - Broad brush strokes. PMID- 2270216 TI - Community nurse executives' psychologic well-being: relationships among stressors, social support, coping, and optimism. AB - The purposes of this study were to (1) determine the occupational stressors, coping strategies, and sources and types of social support of nurse executives; (2) compare the sample's level of psychologic symptomatology with norms; and (3) examine the effects of stress, social support, and optimism in predicting psychologic well-being. Public health nursing directors located throughout California participated in the study. Mailed questionnaire booklets were used to collect data from the target population. A subset of the sample participated in face-to-face, taped, structured interviews that elicited additional data on nurse executives' work stress, coping strategies, and social support dimensions. Several significant findings emerged. The mean psychologic symptom score for the subjects was greater than the published norm, suggesting psychologic distress. In regression analysis, total number of years in nursing accounted for 14.8% of the variance in psychologic symptoms, the dependent variable. Level of optimism accounted for an additional 29.8% of the variance. Total hassles and co-worker social support together accounted for 6.57% of the variance in the last step, but were not statistically significant. Interview data identified the major occupational stressors, coping strategies, and sources and types of social support for this group of nursing directors. PMID- 2270217 TI - Care coordination: a resource-intensive component of home health nursing practice. AB - Coordinating patient care is an activity central to home health nursing practice. Nurses believe that this component of care contributes in a meaningful way to patient well-being. Yet changes in the home care environment at the patient, agency, and system levels could jeopardize nurses' care coordination activities. This study describes the nature of the care coordination activities delivered by home health nurses and explicates the amount of time expended in these activities. A convenience sample of 143 nurses, employed in 24 home health agencies in a southeastern state, participated. They recorded their time, in 15 minute intervals, for 10 consecutive working days. On average, they spent 29% of their time in direct care (i.e., home visits), 18% in travel, 18% in record keeping activities, and 16% in care coordinating activities. New mechanisms to reimburse home care are on the horizon. Studies such as this that begin to explicate the nature of care requirements are critical if appropriate decisions are to be made about the structure of a reimbursement system for home health care. PMID- 2270218 TI - Family-carried growth records: a tool for providing continuity of care for migrant children. PMID- 2270219 TI - Nurse-client interactions in community-based practice: creating common ground. AB - Although research activity is increasingly aimed at examining health outcomes of community health nursing care, little empirical literature systematically describes the nurse-client interaction. In this pilot study nurse-client interactions were evaluated to describe their detailed elements. Nineteen such interactions occurring in a Canadian public health department were videotaped by a professional filming crew. The clinical situations included home visits, school health interviews and screening, health classes, and clinic work. The audio portion of the nurse-client exchanges were transcribed from the videotapes onto a computer and analyzed using content analysis. Semi-structured interviews were conducted with nurses and clients after the filming to elicit their perceptions of the interactions. Field notes describing nonverbal and contextual data were also collected and analyzed. The central process identified during the interactions was called "creating common ground." This integrating conceptual schema captured the give and take as each participant defined territory and revealed information. The process varied depending on care context, process skills of the nurse, and willingness of the client to engage. PMID- 2270220 TI - Patterns of fecal coliform contamination in day-care centers. AB - During a six-month period, on four separate occasions, six licensed day-care centers had cultures taken from environmental surfaces as well as the hands of children and teachers. Fecal coliforms were recovered from 64 (9.5%) of the 675 surfaces sampled. Recovery rate was not influenced by a center's socioeconomic status, time of year, or presence of children who were not toilet trained. Recovery rates did differ significantly in different areas, with the kitchen showing a relatively high recovery rate (19%), and toys and toilets showing remarkably low rates (2% and 4%). Centers with formal hand-washing procedures had lower recovery rates than those without such practices. We also demonstrated a high recovery rate from hands of staff (16%); 6% of children had positive cultures. Contamination of hands and classroom objects is a potential source for the transmission of enteric diseases for children in day-care centers. A program directed at reducing contamination would be important in preventing the spread of diarrheal illness. PMID- 2270221 TI - A study of community differences in stress among the elderly: implications for community health nursing. AB - It has long been known that stressful states are linked to physical and mental health. An important dimension of emotional stress is community environment. That is, communities can produce stress in individuals but can also provide the coping resources that help modify these stressors. We examined differences in stress responses among a random samples of 900 elderly living in nine metropolitan and nine non-metropolitan, randomly chosen communities in six northeastern states. Respondents were asked if, in the past year, they had experienced anything upsetting or stressful in their lives connected with family and friends, their health, and their finances. The findings support the existence of community differences in stress responses for these elderly respondents, and show evidence of a link between community structure and individual behaviors. PMID- 2270222 TI - Challenges for continuing education of public health nurses in Florida. AB - Perceived continuing education needs among public health nurses at the staff and supervisory levels were investigated. A questionnaire was adapted for each and administered at participating county public health units. Results indicated a high level of agreement between staff nurses and supervisors. Further analysis of the data suggested a relationship between the nurses' perception of continuing education needs and the realities of their nursing practice. Public health nurses, educators, and administrators face the challenge of refocusing continuing education needs and activities on the broad scope of this area of specialty. PMID- 2270223 TI - Relationship between cross-cultural health attitudes and community health indicators. AB - Improving health standards both nationally and cross-culturally is a goal for all community health nurses. Previous research has supported links between health attitudes and behavior. The purpose of the present study was to investigate the relationship between attitudes toward health and indexes of community health using a cross-cultural data set. Concepts selected from the data set were I (myself), body, sickness, disease, life, doctor, health, medicine, hospital, nurse, death, and insane. Community health indicators were male and female life expectancy, infant mortality, economic and public health expenditures, and net social progress. The original sample included 1200 high school males within each of 30 language and cultural communities. Data were derived from students' ratings of the dimensions of evaluation, potency, and activity for each concept. The results supported the association between attitudes and objective community health indicators. Unexpected negative correlations were found between attitudes toward medicine and nurse attitudes toward body and life, perhaps indicating that extended contact with health care providers may result in negative attitudes toward them. Positive relationships were found between public health expenditures and nurses, indicating that in countries with more expenditures for community and public health, attitudes toward nurses were more positive. PMID- 2270224 TI - The development of nursing diagnoses for aggregates and groups. AB - A focus on aggregates, groups, or communities as clients is an important characteristic of community health nursing practice. Community health nurse practitioners have identified population groups as one of five functional components in a typology of community health nursing practice. Questions have been raised, however, as to whether such groups need different forms of nursing diagnoses than those used for individuals. We attempted to use nursing diagnoses in a senior community health nursing course with undergraduate students that included experience working with aggregates or groups. Issues were identified in relation to the scope of the role of nurses in the community, the selection of the client, and the use of a taxonomy. PMID- 2270225 TI - Ethics committees in home health agencies. AB - Home health care providers are increasingly faced with ethical dilemmas. Advancing technology, fiscal allocation guidelines, and patients requiring more complex care influence the delivery of services. Nurses providing home health care frequently must practice independently, and the possibility that they may not be adequately prepared in ethical decision making compounds the problem. As was the case in hospitals a decade ago, it is time to develop ethics committees in home health care agencies. PMID- 2270226 TI - Characterization of a 56-kb plasmid of Erwinia amylovora Ea322: its noninvolvement in pathogenicity. AB - A plasmid from Erwinia amylovora strain Ea322, pCPP60, was studied for its involvement in the phytopathogenicity of this strain. Eviction through incompatibility and curing with acridine orange did not affect the pathogenic capability of Ea322. The plasmid was characterized as self-transmissible with a narrow host range. Hybridization of its origin of replication with plasmids of different incompatibility groups revealed affiliation with IncF. The exact subgroup was not determined, although it does not belong to IncFI, IncFII, IncFIV, or IncFV. A sequence of 800 bp, required for conjugation in cis, was cloned in pUC9. A "miniplasmid" containing the origin of replication in a 1.2-kb sequence was constructed. Its high copy number was in contrast with the stringently controlled copy number of the native plasmid of one to three copies per chromosome equivalent. PMID- 2270227 TI - Selection of independent plasmids determining phenol degradation in Pseudomonas putida and the cloning and expression of genes encoding phenol monooxygenase and catechol 1,2-dioxygenase. AB - Long-term cultivation of the Pseudomonas putida multiplasmid strain EST1020 on phenol resulted in the formation of individual PHE plasmids determining phenol degradation. Four types of PHE plasmids, pEST1024, pEST1026, pEST1028, and pEST1029, are characterized. They all contain a transferrable replicon similar to pWWO-8 with a partly duplicated DNA sequence of the 17-kb transposable element of this plasmid and include various amounts of DNA that carry genes encoding phenol degradation (phe genes). We cloned the genes determining phenol monooxygenase and catechol 1,2-dioxygenase from the Pseudomonas sp. parent strain plasmid DNA into the broad host range vector pAYC32 and studied the expression of the cloned DNA. The formation of a new hybrid metabolic plasmid, pEST1354, was demonstrated in P. putida PaW85 as the result of transposition of the 17-kb genetic element from the chromosome of PaW85 into the plasmid carrying cloned phe genes. The target site for the 17-kb transposon was localized in the vector DNA, just near the cloning site. In subcloning experiments we found two regions in the 17-kb DNA stretch that are involved in the expression of the cloned phe genes. PMID- 2270228 TI - A mitochondrial DNA rearrangement and three new mitochondrial plasmids from long lived strains of Podospora anserina. AB - The excision-junction sites of a mtDNA rearrangement of a long-lived strain of Podospora anserina, Mn19, were cloned and sequenced. Analysis of sequence and hybridization data lead to the conclusion that the Mn19 mtDNA consists of two nonoverlapping circular molecules. Three plasmids, LMt-2, LMt-3, and LMt-4, cloned from long-lived progeny of crosses between the Mn19 strain and wild type were cloned and sequenced. These plasmids share features and excision-junction sites with previously described longevity and senescence plasmids. The Mn19 mtDNA rearrangement and plasmids LMt-2, LMt-3, and LMt-4 are described. The possible significance of similarities to previously described plasmids is discussed. PMID- 2270229 TI - Plasmid-associated aggregation in Thermus thermophilus HB8. AB - Thermus thermophilus HB8, a moderate thermophile, exhibits visible aggregation when growing on a rich broth. Strain HB8 also contains two cryptic plasmids. We isolated cured strains from HB8 and observed that loss of the 47-MDa plasmid was correlated with loss of aggregation. An enrichment procedure was developed for aggregating cells and used to demonstrate that aggregation was restored upon transformation of a cured strain with plasmid DNA. The aggregation phenotype of transformed cells was variably stable; most did not retain either the plasmid or the phenotype for prolonged periods of growth. Hybridization experiments using a partial sequence from the 47-MDa plasmid suggested the presence of a repeated DNA sequence on this plasmid and on the chromosome. This is the first report of a phenotype associated with a plasmid from a Thermus strain. PMID- 2270230 TI - An M13 vector library for cloning DNA with four nucleotide 3' overhangs. AB - A flexible M13 vector library incorporating the BstXI site has been developed. DNA cut by any currently commercially available restriction endonuclease that generates a 4-nucleotide (nt) 3' overhang can be ligated into a specific clone of the library. The BstXI enzyme recognizes a 6-bp bipartite palindromic sequence. The central nucleotides are not specified, and form a 4-base, 3' overhang when cut by BstXI. 5' CCANNNNN NTGG GGTN NNNNNACC 5' Since the 4-base overhang formed is not part of the BstXI recognition sequence, it is possible to generate a library of 256 different clones by introducing the BstXI site, 151 of the possible 256-member library have been isolated, including all 13 M13BF clones in which the overhang formed by BstXI digestion is complementary to those formed by currently available restriction endonucleases. Of these 13 vectors, BstXI digestion of six clones results in nonpalindromic cohesive ends and should facilitate in vitro tandem gene amplification. The BstXI site is adjacent to the four codons corresponding to the factor Xa recognition sequence. Hence the vector library could facilitate the expression of a fusion protein that could be proteolytically cleaved by factor Xa. PMID- 2270231 TI - Nucleotide sequence of the rep gene of staphylococcal plasmid pCW7. AB - Previous heteroduplex mapping studies showed that staphylococcal plasmid pCW7 belongs to the pT181 family of small antibiotic resistance plasmids which replicate by a rolling-circle mechanism. Replication in each case is initiated at the plasmid origin (ori) by a plasmid-encoded protein. Rep, which makes a sequence-specific single-stranded nick to form a covalent Rep-ori replication intermediate. A comparison of sequencing results for the repN gene of pCW7 with data for the products of five other homologous rep genes allows a prediction to be made of the segments of the primary structure of Rep which are likely to be responsible for plasmid-specific recognition of the ori region by each Rep protein. PMID- 2270232 TI - Methodological problems in AIDS behavioral research: influences on measurement error and participation bias in studies of sexual behavior. AB - An unprecedented number of human sexuality studies have been initiated in response to the acquired immune deficiency syndrome (AIDS) epidemic. Unfortunately, methodological developments in the field of sex research have been slow in meeting the demands of AIDS investigations focusing on the diverse populations at risk for infection with the human immunodeficiency virus (e.g., adolescents, gay men, intravenous-drug users, ethnic minorities, elderly transfusees). In this article, we review and integrate current literature on measurement error and participation bias in sex research, with an emphasis on collecting sexual information in the context of AIDS. The relevance of these findings for AIDS-related sex research is discussed, and recommendations are made to guide future investigations. PMID- 2270233 TI - Stress, emotion, and human immune function. AB - This article provides a review of empirical evidence linking emotional processes to immune function in humans. Acute stressors have produced mixed effects on immunity, presumably through differential activation of physiological stress systems. Chronic stress has been associated with suppression of immune function, and there is evidence that the immune system may not adapt over time. Effects of stress accompanying social disruption and psychological depression, when demonstrated, have been consistently adverse. Certain personality styles may enhance or degrade immune response. Relationships between psychosocial factors and immunity have been identified for several diseases, including cancer, acquired immune deficiency syndrome, and autoimmune diseases; psychosocial interventions have been tested with variable results. Theoretical and methodological considerations are summarized and directions for future research suggested. PMID- 2270234 TI - Alcohol challenge with sons of alcoholics: a critical review and analysis. AB - Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH-). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH- individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ subjects find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop. PMID- 2270235 TI - Psychological approaches to panic disorder: a review. AB - Panic disorder has been the subject of considerable research and controversy. Though biological conceptualizations have been predominant, psychological theorists have recently advanced conditioning, personality, and cognitive hypotheses to explain the etiology of panic disorder. The purpose of this article is to provide an empirical and conceptual analysis of these psychological hypotheses. This review covers variants of the "fear-of-fear" construal of panic disorder (i.e., Pavlovian interoceptive conditioning, catastrophic misinterpretation of bodily sensations, anxiety sensitivity), research on predictability (i.e., expectancies) and controllability, and research on information-processing biases believed to underlie the phenomenology of panic. Suggestions for future research are made. PMID- 2270236 TI - Behavioral approaches to neuropsychological rehabilitation. AB - Behavioral approaches have been applied to a wide variety of behavioral and cognitive disturbances resulting from brain damage or disease. This article provides a comprehensive and critical review of the literature concerned with behavioral interventions in neuropsychological rehabilitation. The article examines six categories of target behavior: inappropriate social behavior, attention and motivation, unawareness of deficits, memory, language and speech, and motor disturbance. The efficacy of behavioral approaches for treatment of the neurologically impaired and implications for the future role of behavioral approaches in neuropsychological rehabilitation are discussed. PMID- 2270237 TI - The case for motivated reasoning. AB - It is proposed that motivation may affect reasoning through reliance on a biased set of cognitive processes--that is, strategies for accessing, constructing, and evaluating beliefs. The motivation to be accurate enhances use of those beliefs and strategies that are considered most appropriate, whereas the motivation to arrive at particular conclusions enhances use of those that are considered most likely to yield the desired conclusion. There is considerable evidence that people are more likely to arrive at conclusions that they want to arrive at, but their ability to do so is constrained by their ability to construct seemingly reasonable justifications for these conclusions. These ideas can account for a wide variety of research concerned with motivated reasoning. PMID- 2270238 TI - Ethnic identity in adolescents and adults: review of research. AB - Ethnic identity is central to the psychological functioning of members of ethnic and racial minority groups, but research on the topic is fragmentary and inconclusive. This article is a review of 70 studies of ethnic identity published in refereed journals since 1972. The author discusses the ways in which ethnic identity has been defined and conceptualized, the components that have been measured, and empirical findings. The task of understanding ethnic identity is complicated because the uniqueness that distinguishes each group makes it difficult to draw general conclusions. A focus on the common elements that apply across groups could lead to a better understanding of ethnic identity. PMID- 2270239 TI - Obtaining meaningful results from Fourier deconvolution of reaction time data. AB - The technique of Fourier deconvolution is a powerful tool for testing distributional predictions of stage models of reaction time. However, direct application of Fourier theory to reaction time data has sometimes produced disappointing results. This article reviews Fourier transform theory as it applies to the problem of deconvolving a component of the reaction time distribution. Problems encountered in deconvolution are shown to be due to the presence of noise in the Fourier transforms of the sampled distributions, which is amplified by the operation of deconvolution. A variety of filtering techniques for the removal of noise are discussed, including window functions, adaptive kernel smoothing, and optimal Wiener filtering. The best results were obtained using a window function whose pass band was determined empirically from the power spectrum of the deconvolved distribution. These findings are discussed in relation to other, nontrigonometric approaches to the problem of deconvolution. PMID- 2270240 TI - Truth and consequences of ordinal differences in statistical distributions: toward a theory of hierarchical inference. AB - A theory is presented that establishes a dominance hierarchy of potential distinctions (order relations) between two distributions. It is proposed that it is worthwhile for researchers to ascertain the strongest possible distinction, because all weaker distinctions are logically implied. Implications of the theory for hypothesis testing, theory construction, and scales of measurement are considered. Open problems for future research are outlined. PMID- 2270241 TI - [Women, health and public policy: practices and strategies in Puerto Rico]. PMID- 2270242 TI - [Violence against women because of their being women. Myths and stereotypes perpetuated in "El Vocero"]. AB - A model is presented for examining the myths, sterotypes, and prejudices about women that are presented daily to our society through the popular press, specifically The Vocero. The journalistic vocabulary and style, the interpretation of the information offered and the significance of the information omitted in the Vocero articles are examined. The myths and stereotypes of women that are repeated consistently in these articles are correlated with the clinical experience of the Puerto Rico Rape Crisis Center and Casa Julia Battered Woman's Shelter. Finally, this process of popular education is presented as an important determinant for violence against women in Puerto Rico and for the prevalence of a high degree of social apathy and indifference to the problem in our community. PMID- 2270243 TI - [Participation of Puerto Rican women in the labor force and its health risks]. AB - Using data provided by the State Insurance Fund of Puerto Rico, the authors analyzed the risks related to their jobs of the employed female population changes over time and differences by sociodemographic characteristics and by sex. Rates of cases informed at the Fund were calculated and used as a "proxy" of risk. Results indicate that women have lower risks of health conditions associated with their employment than men. Younger and single women have higher risks than workers in the other age groups and marital statuses. Risks for women seem to be higher in those industries where they have just recently engaged and in those that demand skills which women lack. Rates of informed cases to the fund have decreased since the seventies for employed males, while for women they remained relatively stable in the seventies and decreased in the eighties. PMID- 2270244 TI - [Health and work: the case of the gas emissions at the Industrial Complex of Mayaguez]. AB - This article describes the effects of gas emissions on the health of the workers (mostly women) of garment Industry at the Guanajibo Industrial Complex in Mayaguez. The persons affected show the following diseases and conditions: peripherial neuropathy, alteration of time and space orientation, damage to the pulmonary system and the respiratory tract, allergies, degenerative diseases, and even death. The agencies concerned have been negligent alleging that the problem is caused by stress of mass hysteria, this without performing the necessary studies. Having evaluated the problem, the Committee concludes that its roots are in the establishment in Puerto Rico of industries without considering the negative effects over health due to the contamination they generate, and which they do not control properly, all to maintain jobs that in the long run will not solve our problems, but will surely affect the health of the people. PMID- 2270245 TI - [Reproductive disorders in women working at the Industrial Free Zone, San Pedro de Macoris, Dominican Republic, 1989]. PMID- 2270246 TI - [Health status of the elderly female population in Puerto Rico]. PMID- 2270247 TI - [Public policy and elderly women]. AB - Talking about the aging population is talking about aged women. The census data in Puerto Rico reflects a considerable increase in this population sector. This increase represents a challenge to the provision of human services and to the formulation and implementation of public policy to this cohort. The public policy should be guided to end the existing inequality among sexes, recognize and deal adequately with the particular needs of the elderly women. Three areas of the public policy that are essential regarding the elderly women are: economic security, health care, and social services. PMID- 2270248 TI - [Informal support systems for Puerto Rican elderly women: implications for the health care delivery system]. AB - This article presents a qualitative analysis of the informal networks of support of older Puerto Rican women. It focuses on the support offered by adult children to their aged mothers. Cultural definitions about female and male roles affect the types of exchange that occur within the family. The elderly mothers expect and receive more help from their daughters than their sons. The daughters feel pleased by the fact that they are able to assist their mothers yet, many indicated that in certain occasions they feel stress. PMID- 2270249 TI - [Julia de Burgos' subjectivity and praxis: an approach to the social creation of her health]. PMID- 2270250 TI - [Sex discrimination in health occupations in Puerto Rico]. PMID- 2270251 TI - ["Pink collar" medicine: implications of the feminization of the profession]. AB - The rising number and proportion of women in medicine has implications for patient care as well as for the health care delivery system as a whole. Women physicians tend to establish more reciprocal relationships with patients, and are more likely to listen to psycho-social problems than their male colleagues. Other gender-based differences are evident in the practice settings and sites chosen by the two sexes. Women cluster in certain specialties, and are more likely to locate in urban areas and have salaried practices. They also work fewer hours and have lower incomes than their male counterparts. These differences have created heirarchical distinctions within the medical profession. This in turn suggests the possibility of the creation of a "pink collar" medicine. PMID- 2270252 TI - [Autonomy among nursing staff: moments and actions]. AB - The work Autonomy in Nursing: Moments and Actions presents three points of view: positions assumed by nurses, nursing's evolution and the stereotyped image society has that constitutes a barrier to the progress of nursing. The paper presents local, national and international moments and actions that are evidences of nursing autonomy. The work also presents past glorious moments that as presented by investigators demonstrate barriers for the accomplishments of that desire autonomy. Finally the paper calls the group attention for actions for the 21st. century, that will prove that nurses belong to an altruist group prepare to assume the responsibility of its actions in accordance to the plans they are expected to fulfill. PMID- 2270253 TI - [The feminist practice]. AB - A discussion on contemporary feminism and feminist critical practice is proposed. The most significant aspects of debate on the constitution, reproduction, opposition and resistance in feminism are exposed. The most outstanding characteristics of anglo-american and french feminism are presented. Its implications for feminist practice are considered. No definitive conclusions arise. New theories and multiple explanations are suggested as constant methods to analyze an ever changing discussion. PMID- 2270254 TI - [Female sexuality before and after AIDS]. PMID- 2270255 TI - AIDS prevention program for Puerto Rican women. AB - Historically women are considered the family's primary care provider and biologically, they are the link in the transmission of the Human Immunodeficiency Virus. Because of this dual role, they need programs that are culturally sensitive and effective. Many Latinas do not perceive themselves to be at risk despite the educational resources available to them. This article examines cultural factors that influence risk perception and behavioral changes in response to educational intervention. Interviews and literature review were used in assessing availability, applicability and cultural sensitivity of AIDS prevention programs. Effective programs need to be culturally sensitive to gender role expectation and the role of motherhood for Latinas. Educators expressed the belief that women benefit most from programs that help them implement the behaviors that will help protect them. Programs must be cognizant of the cultures' demand for respect and modesty while providing factual information/instruction. PMID- 2270256 TI - [AIDS-related mortality among Puerto Rican women in New York City, 1981-87]. AB - The present study analyzes the impact of AIDS on the mortality experience of Puerto Rican women in New York City for the time period 1981-1987. This study shows that Puerto Rican women in New York City are at higher risk for AIDS than any other racial or ethnic group. Economic and sociocultural factors in the Puerto Rican community related to the use of intravenous drug use, as well as trends in migration and marriage, are associated to the high risk of AIDS in this group. This information is of particular interest for Puerto Rico and New York City given the migration patterns of Puerto Ricans traveling between Puerto Rico and New York City. PMID- 2270257 TI - [Women and AIDS; a critical view]. PMID- 2270258 TI - [Birth spacing in Puerto Rico]. AB - This paper uses life table methods to analyze the process of family formation in Puerto Rico. Despite a continuing decline in fertility, the pattern of birth spacing is very rapid with a big proportion of short intergenesic intervals. This indicates a clear distinction between spacing and stopping behavior. Some possible health implications are discussed. PMID- 2270259 TI - [Sterilization and contraceptive practice in Puerto Rico, 1982]. PMID- 2270260 TI - [The impact of cesarean section on fertility in Puerto Rico]. PMID- 2270261 TI - [Induced abortion in Puerto Rico 1985]. PMID- 2270262 TI - [Female physiology during exercise]. AB - Physiological responses and adaptations of women to exercise are influenced by her genetically determined morphological and functional characteristics, and by her level of physical fitness. Physiological responses of women during submaximal and maximal exercise differ quantitatively from those of men but adaptations to training are qualitatively similar in both. Studies demonstrate that differences between the sexes in performance of athletic events that require high aerobic or anaerobic capacity are due, to a large extent, to differences in body structure and composition: the average woman is smaller and lighter and has less muscle mass than the average man. These characteristics influence physiologic responses of the musculoskeletal, cardiovascular and respiratory systems during exercise. This article describes physiological responses of women during exercise in relation to her sex related morphological characteristics, and the adaptations that occur with physical training. PMID- 2270263 TI - Climacteric and menopause--medical point of view. AB - A discussion of the problems associated with the menopause and a regime to combat its effects is described. Treatment of the psychological aspects of menopause is stressed as well as the estrogen-replacement therapy. PMID- 2270264 TI - [Are Puerto Rican women healthier than men?]. PMID- 2270265 TI - [The unknown facts: women's participation in the health professions in Puerto Rico (1898-1930)]. PMID- 2270266 TI - [Women-health-society]. PMID- 2270267 TI - Social relations and empowerment of sexual partners of i.v. drug users. AB - This paper examines social relations and roles of women sexual partners of IV drug users. It is argued that the Island socio-cultural environment does not provide the socio-structural conditions for individuals to organize groups and get the power to solve community problems. It is further assumed that individuals have resources in some of the positions they occupy. Therefore, ascertaining which resources are prevalent in which positions will allow interventionists to start the empowerment process. The data shows that IV drug users' sexual partners have a steady income from food stamp programs. They support the family, are heads of households, and are responsible for child rearing. The paper discusses how these resources can be used to start women getting the power to solve their problems and consequently prevent HIV transmission. PMID- 2270268 TI - [The cytogenetic effect of chronic irradiation revealed using an analysis of the first two mitoses in the root meristem of germinating seeds of Crepis tectorum from the 30-kilometer zone of the accident at the Chernobyl Nuclear Power Station]. AB - Peculiarities of the appearance of C. tectorum rootlet in the course of seed germination have prompted the authors to use the method of continuous germination of seeds in 0.01% colchicine solution and to analyze chromosome aberrations in the first tetraploid cells derived from early dividing cells. Since it has been shown that cells of the embryo's root meristem of dormant Crepis tectorum seeds are at the G1 stage, the observed, by the method used, chromatid aberrations in the cells that early enter mitosis, are probably induced by the incorporated radioactive products at stages S and (or) G2 during seed germination. PMID- 2270269 TI - [Cytogenetic effects in native populations of Crepis tectorum exposed to chronic irradiation in the vicinity of the Chernobyl Nuclear Power Station. Induction of chromosome aberrations during the first 2 years following the accident]. AB - During the first year after the accident the maximum frequency of Crepis tectorum cells with chromosome aberrations amounted to 10.2 to 15.3% at a dose-rate of 5 10 mR/h (gamma-radiation), cells with multiple aberrations being rather frequent. During the second year, in the areas where a dose-rate was 20 to 0.02-0.03 mR/h, the number of cells with chromosome aberrations amounted to 1.4-2.2% at the highest dose-rates. Besides, plants were found with the altered karyotype which was indicative of active microevolutionary processes in chronically exposed populations. PMID- 2270270 TI - [Dynamics of the indices of lipid peroxidation in the blood and radiosensitive organs of rats exposed to total and local x-irradiation]. AB - There are variations in the radiation response of lipid peroxidation (LPO) indices. The initial rise of spontaneous chemiluminescence (SCL) immediately after whole-body irradiation (8 Gy) is followed by its rapid drop below the initial level. A considerable increase of the LPO level in the blood, spleen and thymus occurs 24 hr or 2 days after irradiation. The decrease on day 7 is followed by the increase on day 14. The periods of LPO inhibition (15 to 60 min and 7 days after irradiation) correspond to two waves of the hypersecretion of catecholamines and glucocorticoids that have antioxidant activity. With local irradiation of rat skin (a single exposure to 50 Gy) the SCL and malondialdehyde intensity peaks in blood serum are the same as those observed after whole-body irradiation, whereas in the spleen and thymus, these indices regularly decrease. There are peculiarities in the dynamics of triboluminescence in rat blood and organs that is attributed, in addition to LPO, to the effect of radiation on the electric parameters of tissues. PMID- 2270271 TI - [Proteinase activity of the peripheral blood cell nuclei of gamma-irradiated rats]. AB - Immediately after gamma-irradiation of rats a dose-dependent increase in the activity of alkaline and Ca-dependent proteinases was exhibited by leukocyte nuclei. In nuclei of granulocytes, in contrast to those of lymphocytes, radiation activation of proteinases was more pronounced. PMID- 2270272 TI - [Phospholipids in the nuclei and chromatin of the rat thymus at long periods following gamma-irradiation]. AB - The phospholipid content of the homogenate, nuclei and chromatin of rat thymus was being studied during three months after fractionated gamma-irradiation (2 Gy X 3 at a week interval). The number of phospholipids in the total fraction of phosphatidyl choline + phosphatidyl serine and phosphatidyl ethanolamine in the nuclei and chromatin of rat thymus was shown to decrease 60 min following the last exposure. In a month the phospholipid content in the nuclei and chromatin increased up to the control level keeping it throughout the entire period of observation. PMID- 2270273 TI - [Reproductive death of the apoptosis type in irradiated cells of the BW5147 thymoma]. AB - The method of flow cytofluorometry and biochemical analysis were used to study the pattern and kinetics of the postirradiation death of proliferating BW5147 lymphoid cells. Irradiation with a dose of 10 Gy was shown to induce thymoma cell death by apoptosis. Radiation-induced synchronous transfer of part of cells from G1 to S-stage and blocking of all cells at G2/M stages of the cell cycle preceded the cell death. Decreasing of the growth factor content in a medium through its depletion or cultivation in conditions of low serum content accelerated cell death. A possible relationship between cell death and proliferation is discussed. PMID- 2270274 TI - [The participation of oxygen in the process of the interphase death of T lymphocytes following irradiation in vivo]. AB - The ability of lymphocytes to inhibit proliferation of non-syngeneic stem cells decreases differently after exposure in vivo and in vitro. The causes of the observed differences and the mechanism of radiation impairment of this function under different irradiation conditions have been investigated. Cells exposed in vivo die in the interphase irreversibly. The newly formed lymphocytes start the repair process as late as one month after irradiation. The injury to in vivo exposed cells is severer due to the presence of oxygen in tissues. A definite time interval is needed for the damaging effect of oxygen radicals to be implemented: the effect is maximum as early as 4 h following irradiation. With in vivo exposure under hypoxic conditions the functional activity of lymphocytes is the same as that of lymphocytes irradiated in vitro with the same dose. In vitro irradiation of lymphocytes at a high oxygen content causes a decrease in the functional activity of cells. PMID- 2270275 TI - [The effect of ionizing radiation on the respiration of rat thymocytes]. AB - The oligomycin-sensitive component of the rate of oxygen consumption by rat thymocytes increased by 22% after X-irradiation. The postirradiation increase in the thymocyte respiration rate was connected with the impairment of a balance between sodium, potassium and calcium and with the protein synthesis activation, and was independent of lymphokine production by lipoxygenase. Irradiation was ineffective with respect to electron transport in the respiratory chain and electrogenic leakages through the inner membrane of thymocyte mitochondria. PMID- 2270276 TI - [The radiation modifying properties of carnosine]. AB - The influence of carnosine (beta-alanyl-l-histidine) on the survival rate of albino mice subjected to whole-body X-irradiation has been investigated. Carnosine (50-200 mg/kg/day) administered per os during a period of 20 days before irradiation (5.0 Gy) increased the survival rate by 45-65%, whereas the administration of carnosine within 30 days after irradiation (5.5 Gy) produced an insignificant protective effect and caused inhibition of the postirradiation histamine accumulation in the spleen. PMID- 2270277 TI - [The effect of granulocyte-macrophage colony-stimulating factor on hemopoiesis recovery and the survival of irradiated mice]. AB - A human recombinant granulocytic-and-macrophagic colony-stimulating factor (rGM CSF) administered repeatedly to irradiated (10 Gy) CBA mice increased CFUs and CFU-GM content, the number of bone marrow granulocytes and erythronormoblasts, and spleen and peripheral blood cellularity. The survival rate of exposed (9.7 Gy) mice repeatedly injected with rGM-CSF increased from 25% (control) to 90%. PMID- 2270278 TI - [Radioprotective properties of ubiquinones during acute and chronic irradiation of rats]. AB - Protective and therapeutic effect of ubiquinone-8 was demonstrated on rats exposed to 8 Gy radiation. There was a 16-20% increase in the survival rate of the irradiated rats as compared with the controls. The per os administration of ubiquinone-8 during a five-month period in conditions of chronic exposure arrested the radiation-induced accumulation of lipids in rat liver and somewhat improved the dynamics of the body mass growth in the exposed rats. PMID- 2270279 TI - [The role of the hemopoietic microenvironment on the hemopoiesis-stimulating effect of cystamine]. AB - The influence of cystamine delivered in a radioprotective dose before and after irradiation of mouse-recipients (8 Gy) on the effectiveness of exogenous bone marrow cloning has been investigated. Cystamine administered prior to irradiation exerts a protective effect on CFUs and also causes an increase in the number of splenic colonies grown from CFUs of the transplanted bone marrow. With cystamine administered after irradiation the protective effect is absent, but the CFUs number in the femur increases in recipients transplanted with intact bone marrow in comparison with those transplanted without cystamine. It is believed, that in addition to the specific protective mechanism of action of radioprotectors, there is a nonspecific mechanism of increasing the proliferation of protected stem cells that is connected with the stimulatory effect of radioprotective agents on the haemopoietic stroma elements. PMID- 2270280 TI - [The reparative regeneration of the endothelium of the mouse aorta during microsurgical interventions following local gamma irradiation (based on scanning electron microscopic data)]. AB - In experiments with rats, abdominal aorta was subjected to microsurgical anastomosis after local irradiation with doses of 40 and 50 Gy. Irrespective of the time interval between the operation and irradiation the iatrogenic defect was restored completely. With the operation performed 24 h after irradiation the platelet adhesion decreased, the proliferation was inhibited depending on radiation dose, and the pattern of the endotheliocyte migration changed. The above effects were absent with the operation performed one month after irradiation. PMID- 2270281 TI - [Rates of formation of absorbed doses in the rat body of 241Am, tributyl phosphate and n-paraffins during separate and combined inhalation administration]. PMID- 2270282 TI - [Early transient incapacitation of monkeys exposed to high-energy electrons and gamma-irradiation in supralethal doses]. AB - Irradiation of Macaca fascicularis with electrons (24 MeV, 46 and 104 Gy) and gamma-quanta (60Co, 77 and 138 Gy) caused early transient incapacitation (ETI) and severe symptoms of neurological disturbances. Two types of the ETI clinical patterns were distinguished: a dyskinetic type marked by ataxia; and a severer, comatose type manifested by disappearance of voluntary movements, areactivity, and temporary loss of reflexes. PMID- 2270283 TI - [The electrical activity of the monkey brain in the period of early transient incapacity during gamma-irradiation at high dose rates]. AB - Changes in the electroencephalogram (EEG) of Macaca fascicularis during early transient incapacitation (ETI) were shown to correlate with the dynamics of clinical manifestations of the damage. Irradiation caused desynchronization of EEG followed by a generalized retardation of its fluctuations reaching the maximum at the height of ETI. EEG disturbances in animals during the comatose phase of ETI indicated a severe inhibition of the brain cortex functional activity. PMID- 2270284 TI - [Radiation-induced lipid peroxidation, a fish diet and modulation of the effects by vitamin E]. AB - Data are presented in this paper on the effect of vitamin E on rats given a fish diet after whole-body gamma-irradiation. The content of lipid peroxidation products in rat plasma, brain and liver and also the content of vitamin E have been investigated. Irradiation increases lipid peroxidation in the studied tissues and decreases vitamin E content. This process is aggravated by the fish diet. Vitamin E given in addition to fish diet helps the organism to stabilize the antioxidant homeostasis at a qualitatively different level. PMID- 2270285 TI - [Mathematical modeling of the dynamics of mammalian mortality in the intestinal form of radiation sickness]. AB - A mathematical model has been developed to describe the death rate dynamics in irradiated mammals. The model links statistical biometric functions with statistical and dynamic characteristics of the organism's "critical" system. There is an agreement between the results of modelling and experiments with respect to death rate dynamics of small laboratory animals subjected to acute and chronic irradiation with doses and dose-rates at which small intestine epithelium is "critical". PMID- 2270286 TI - [Cytogenetic effects of UV laser radiation with wavelengths of 248, 223 and 193 nm on mammalian cells]. AB - Ten hours after irradiation of mouse cornea with doses of 0.09 to 1.5 J/cm2 the incidence of cells with chromosome aberrations increased linearly with dose and amounted to 11.7% at 248 nm, 5.5% at 223 nm and 2.6% at 193 nm per 1 J/cm2. No induced chromosome aberrations occurred 72 hr following irradiation. Within the dose range from 3.0 to 18 J/cm2 the cytogenetic effect of radiation was less manifest than that with the doses mentioned above, the frequency of chromosome aberrations being independent of either wave length or radiation dose and amounted to 2.5 to 3.0%. PMID- 2270287 TI - [Adenylate cyclase activity of the plasma membranes of lung tissue at lengthy periods following non-lethal gamma-irradiation of rats]. AB - Basal and stimulated activity of adenylate cyclase (cyclizing ATP-pyrophosphate lyase, E.C. 4.6.1.1., AC) in plasma membranes of pulmonary tissue was being studied during a year after fractionated irradiation of rats (2 GyX3). Basal and hormone-stimulated activity of AC was shown to vary significantly from normal 6 and 12 months after irradiation. The exposed membranes responded differently to AC activation by isoproterenol and F-. PMID- 2270288 TI - [Infection of repair-deficient human cells by the vaccinia virus decreases the formation of gamma-induced DNA breaks]. AB - The alkaline elution method was used to study DNA breaks induced by the different mutagens in human cells. Normal fibroblasts and fibroblasts from patients with homocystinuria, deficient in gamma-type repair were shown to be resistant to gamma-radiation after the vaccinia virus infection. In both cell lines there was a decrease in the number of the mutagen-induced DNA breaks. PMID- 2270289 TI - [Increasing the concentration of free calcium in thymocytes during gamma irradiation may induce their death]. AB - Free Ca2+ concentration in thymocytes increased 0.5-1.5h after gamma-irradiation (10 Gy) as was measured by Quin-2AM fluorescent probe. Cycloheximide, a protein synthesis inhibitor, suppressed Ca2+ increase and inhibited radiation-induced thymocyte death. EL-4 thymoma cells did not exhibit any changes in free Ca2+ concentration and interphase death after gamma-irradiation. It is believed that the radiation-induced increase of free Ca2+ concentration in thymocytes may induce their death. PMID- 2270290 TI - [Formation and study of the dosimetric characteristics of wide fields of fast electrons used to irradiate laboratory animals using the LUE-25 accelerator]. AB - A mode of formation of wide fields of fast electrons at LUE-25 accelerator is proposed to expose uniformly the extended 4 cm thick biological objects. Dosimetric characteristics of the electron beams have been studied by film and ferrous-sulfate dosimeters. The potencies and limitations of using the dosimeters as a "witness" are discussed. PMID- 2270291 TI - [The effect of enriching the rations of CBA mice with synthetic beta-carotene on their survival when exposed to gamma-irradiation]. PMID- 2270292 TI - [Evaluation of metabolic efficiency of the liver in patients with psoriasis by the antipyrine test]. AB - In 47 patients with generalized psoriasis vulgaris and 23 healthy subjects the effectiveness of the hepatic metabolism reflected by drug biotransformation was assessed with the antipyrine elimination test. In the group of psoriatic patients there were 25 men and 22 women and in the control group--age-matched 12 men and 11 women. The half-time of antipyrine was longer and the clearance index was lower in the patients than those in the control group. The differences were statistically significant. After 2 weeks of PUVA or SUP-therapy the differences were more significant. The findings indicate an impairment of the liver metabolic effectiveness reflected by drug biotransformation in psoriatic patients. PMID- 2270293 TI - [The role of arachidonic acid metabolites in the skin]. AB - The metabolism of the arachidonic acid (AA) in normal skin is presented, and the role of its metabolites (eicosanoids) in pathogenesis of psoriasis is reviewed. Beside, possibility of the treatment of psoriasis by means of fish oil and eicosapentaenoic acid (EPA) is discussed. PMID- 2270294 TI - [Immunopathological studies of the skin of patients with pemphigoid at different stages of the disease]. AB - The aim of the investigation was to demonstrate whether there is a correlation, in patients with bullous pemphigoid (BP), between the presence of immune deposits in the skin and the activity of the pathological process. We investigated 39 cases with a BP anamnese dating from 3 months up to 17 years. We repeated the investigations several times by means of direct immunofluorescence method in different disease activity. It was demonstrated that there is a complete correlation between the disappearance of the immune deposits in the skin and the remission of the disease. Moreover, it has been shown, that the complement disappears earlier than IgG fraction. These results show the role of the antibasement zone antibodies and especially the complement in the inducement of BP lesions. PMID- 2270295 TI - [Increased proteolytic activity of cathepsin D in the skin of rats after administration of various anti-inflammatory drugs]. AB - Cathepsin D activity and type I and III collagens content in the skin of rats treated with some antiinflammatory drugs (acetylsalicylic acid, phenylbutazone, indomethacin, colchicine and prednisone) were evaluated. It was found that investigated drugs evoke increased activity of cathepsin D and decreased collagen content (mainly type I) in this tissue. The correlation between type I collagen content and proteolytic activity was noticed. PMID- 2270296 TI - [23-year course of lymphomatoid papulosis with transition into T-cell cutaneous lymphoma]. AB - A 63-year old patient who had suffered from mild lymphomatoid papulosis with periods of relapse and spontaneous remissions is presented. After 23 years of that chronic dermatosis he developed a malignant lymphoma covering skin, lymph nodes and internal organs, which was confirmed by histopathological examination. Despite intensive chemo and X-ray therapy the patient died. The importance of continuous follow-up of usually benign lymphomatoid papulosis is stressed. PMID- 2270297 TI - [Chancriform pyoderma as a clinical problem: observation of 45 patients treated at the Dermatology Clinic, Medical Academy, in Cracow 1962-1986]. AB - A clinical, bacteriological and serological pictures of 45 patients with chancriform pyoderma are presented, A single ulcer (92.8%), localized on genitals (91.1%) in adult males (93.3%), imitating or very similar to syphilitic primary chancre in our material was observed. A second case in the literature, of chancriform pyoderma on the dorsal surface of the tongue was recorded. PMID- 2270298 TI - [Results of the treatment of neurosyphilis with high doses of crystalline and procaine penicillins]. AB - The results of the treatment in two groups of patients with neurosyphilis are compared. In 23 cases, i.v. infusions of crystalline penicillin were given for 10 days in daily dose of 20-24 mega U., combined with probenecid. Then it was followed by i.m. procaine penicillin in daily dose of 1.2 mega U., in total dose 12-50 mega U. The mean duration of follow-up was 7,8 months. The second group (34 cases) was treated with procaine penicillin i.m. in daily dose of 1.2 mega U., the total dose was 24-60 mega U. The mean duration of follow-up was 2.5 years. The differences between the results of the treatment in both groups were not significant. In 3 reinfected patients with early asymptomatic neurosyphilis in spite of intensive treatment with penicillin sero- and cerebro-spinal fluid resistant syphilis developed. PMID- 2270299 TI - [Alopecia areata--clinical and immunological characteristics]. PMID- 2270300 TI - Women's use of information regarding hormone replacement therapy. AB - For perimenopausal women, an important decision is whether or not to use hormone replacement therapy (HRT). The decision is complex because HRT involves judgment in weighing gains and losses related to physiological risk. Gains involve relief of hot flashes and prevention of osteoporosis; losses include cancer mortality and side effects of medication. A policy-capturing study of 283 perimenopausal women showed that the factor of most frequent concern was relief of hot flashes. Cluster analyses identified four major groups. Group 4 had an n of 9 and the lowest R2, making interpretation of data questionable. The largest group responded to hot flashes alone; the second to hot flashes and osteoporosis; and the third to hot flashes, somewhat to osteoporosis, but also to side effects of estrogen/progestin therapy. Results indicate nursing interventions should anticipate differences in women's concerns and tailor counseling appropriately. PMID- 2270301 TI - A randomized study to determine complications associated with duration of insertion of heparin locks. AB - A randomized trial was conducted to assess the effect of leaving heparin locks in place longer than 72 hours. Three hundred and one patients were randomly assigned to one of two groups. Group A had the lock changed every 72 hours and Group B had the lock left in place up to 168 hours. Due to withdrawals following randomization, Group A contained 116 subjects and Group B 140 subjects. No significant differences were found between the two groups in relation to age, sex, medical condition, drug used, entries into the lock, minor complications, or incidence of phlebitis. The findings suggest that consideration could be given to extending insertion time up to 96 hours and possibly up to 118 hours. PMID- 2270302 TI - Mutuality and preparedness as predictors of caregiver role strain. AB - Data from 78 older persons and their family caregivers were obtained at 6 weeks and 9 months after hospital discharge. Hierarchical multiple regression was used to determine whether mutuality and preparedness for caregiving were related to lower levels of caregiver role strain. The results indicated that, after controlling for five other variables commonly found to be related to caregiver role strain, mutuality and preparedness ameliorated some but not all aspects of role strain. PMID- 2270303 TI - Psychosocial adjustment of patients and spouses to severe cardiomyopathy. AB - Severe cardiomyopathy (SCM) imposes considerable psychosocial stress on families; however, little is known about the effect of SCM from the point of view of the marital couple. In this study, adjustment to SCM of 90 patients and their spouses was compared. Patients reported more vocational, domestic, and sexual problems than spouses. Spouses reported more problems in health care orientation, family relationships, and psychological distress than patients. The findings indicate that severe cardiomyopathy impacts on the psychosocial integrity of both partners. Therefore, one should plan interventions to support spouses as well as patients. Because problems of spouses and patients may differ, both partners should be assessed to appropriately target interventions. PMID- 2270304 TI - Stress, locus of control, social support, and psychological symptoms among head nurses. AB - This study was conducted to evaluate the relationships among work stress, nonwork stress, locus of control, social support, and head nurses' psychological symptoms. Data were collected from head nurses (N = 300) representing all Army hospitals in the United States; 21% of the volunteer sample were men. The results supported the hypotheses that perceived stress from both work and nonwork sources was positively related to psychological symptoms. Direct effects for both internal locus of control and social support, while weak, were manifest as expected; these variables demonstrated a negative relationship with psychological symptoms. None of the hypothesized buffering effects were detected. The stress model derived from this study accounted for 35.9% of the variance in psychological symptoms. Regardless of gender, the head nurses' psychological symptoms were one standard deviation higher than nonpatient norms. PMID- 2270305 TI - Altered level of consciousness: validity of a nursing diagnosis. AB - The purpose of this three-phase study was to examine the validity of the nursing diagnosis altered level of consciousness (ALC). The conceptual framework was diagnostic reasoning. In Phase I, 26 content experts certified in neuroscience nursing completed four rounds of a Delphi survey to identify defining characteristics and operational definitions for the nursing diagnosis. The diagnosis was divided into ALC: arousal and ALC: content. In Phase II, 30 staff nurses from two neuroscience intensive care units (NICUs) used the magnitude estimation scaling technique in judging the importance and frequency of occurrence of defining characteristics chosen in Phase I. In Phase III, 60 patients in two NICUs were assessed for frequency of occurrence of the defining characteristics for ALC: arousal and ALC: content. In Phase I, there was greater than or equal to 70% agreement on the appropriateness and clarity of 28 and 24 defining characteristics and operational definitions for ALC: arousal and ALC: content, respectively. In Phase II, there were 7 major defining characteristics identified for ALC: arousal and 6 major defining characteristics identified for ALC: content. In Phase III, there were 13 defining characteristics that occurred with significantly greater frequency in patients with an ALC: arousal and 17 defining characteristics that occurred with significantly greater frequency in patients with an ALC: content. PMID- 2270306 TI - The distance to the stomach for feeding tube placement in children predicted from regression on height. AB - Nurses use several external measures referenced to the head and chest to gauge the insertion distance for orogastric and nasogastric (NG) tubes. Few of the measures have been tested. However, in previous studies height was the external measure most correlated with esophageal length both in children and adults. In this study, the ability of previously published regression equations on height to predict esophageal length for NG-tube insertion in 107 children was evaluated. The regression equations were examined for stability, predictive performance, and the likely positions of the tube. The data were heights and esophageal lengths obtained from esophageal manometry records and hospital charts. The predicted values for nasal insertions were biased and averaged 2.4 cm too long (R2prediction = .56, n = 30). Prediction errors greater than 5 cm in absolute value occurred in 25% of the nasally-referenced sample. The predicted values represented overestimates in 18 nasally referenced cases that were 11.5% longer on the average than the measured esophageal lengths. In contrast, the predicted values for the oral insertions were unbiased (R2prediction = .92, n = 77), and gave accurate predictions in the majority of cases. Eighty percent of the oral predictions were within +/- 1.5 cm of the measured esophageal length and represented percentage errors between 0 and 7% (M = 3%, n = 50). PMID- 2270307 TI - Breast self-examination and the health belief model: variations on a theme. AB - Variables derived from the Health Belief Model (HBM) were studied in relation to breast self-examination (BSE) performance, which was measured in terms of both frequency and thoroughness. Data were collected from 202 adult women via self administered questionnaires. Susceptibility and Seriousness were combined to form a "threat of breast cancer" variable, and two approaches were used to compute "net perceived efficacy of BSE." However, barriers and susceptibility in their original form explained more variance in BSE practice than did the combined variables. The negative relationship found between perceived barriers and BSE performance (r = -.44) is consistent with previous findings. Implications for research and practice are presented. PMID- 2270308 TI - Guidelines for the application of ARIMA models in time series. AB - Time series analysis has been suggested as a valuable approach to evaluating the effectiveness of nursing interventions. Time series analysis techniques provide the tools for analyzing unique behavioral fluctuations through time and a framework for predicting future changes in the individual. Because of its newness, time series modeling has not been used widely in nursing research, but it can provide information about processes in nursing practice. Despite the utility of the interrupted time series design, a number of problems frequently arise in view of the practical and inferential difficulties in conducting interrupted time series research. The inherent limitations of time series analysis procedures are discussed in application to research problems. PMID- 2270309 TI - Focus on psychometrics. Internal consistency estimates of reliability. AB - Reliability assessments are appropriate for each research instrument in a study. Measures of internal consistency are a popular set of assessments with Cronbach's alpha being the most favored. Two other measures of internal consistency, theta and omega, have particular characteristics that make their use desirable under certain circumstances. Each of these three measures and its computation is described and examples provided. PMID- 2270310 TI - Re: "Ethnic differences in physiological responses associated with the valsalva maneuver". PMID- 2270311 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee. Minutes of meeting, March 30, 1990. PMID- 2270312 TI - Charter. National Biotechnology Policy Board. PMID- 2270313 TI - Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: proposed actions under the guidelines. AB - This notice sets forth proposed actions to be taken under the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules. Interested parties are invited to submit comments concerning these proposals. These proposals will be considered by the Recombinant DNA Advisory Committee (RAC) at its meeting on October 16, 1990. After consideration of these proposals and comments by the RAC, the Director of the National Institutes of Health will issue decisions in accordance with the NIH Guidelines. PMID- 2270314 TI - Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: actions under the guidelines. PMID- 2270315 TI - Is helodermin-like immunoreactivity in human thyroid C cells due to a salmon calcitonin-like substance? AB - Helodermin-like and salmon calcitonin (sCT)-like immunoreactivities co-existed in a subset of human calcitonin (hCT)-containing cells in normal human thyroid tissue and medullary thyroid carcinomas. Helodermin/sCT-immunoreactive cells were mostly different from calcitonin gene-related peptide (CGRP)-positive cells. Helodermin and sCT immunoreactivities were not identified in pulmonary and pancreatic hCT-positive neuroendocrine tumors, except for a few lung tumor cells showing positive staining with one of two sCT antisera used. Helodermin immunoreactivity demonstrated by rabbit antiserum R0086 was completely abolished in the presence of synthetic sCT, while sCT immunoreactivity was not absorbed by synthetic helodermin. The carboxyl terminal Arg30-Thr31 sequence (and Pro35 amide structure) of helodermin would be the epitopic site recognized by this antiserum, since a similar amino acid sequence is present in sCT molecules but absent from hCT and CGRP. PMID- 2270316 TI - Inhibitory effect of rat amylin on the insulin responses to glucose and arginine in the perfused rat pancreas. AB - Amylin, a 37-amino acid polypeptide, is the main component of amyloid deposits in the islets of Langerhans, and has been identified in the B-cell secretory granules. We have investigated the effect of rat amylin on the insulin and glucagon release by the isolated, perfused rat pancreas. Amylin infusion at 750 nM, markedly reduced unstimulated insulin release (ca. 50%, P less than 0.025), whereas it did not modify glucagon output. At the same concentration, amylin also blocked the insulin response to 9 mM glucose (ca. 80%, P less than 0.025) without affecting the suppressor effect of glucose on glucagon release. The inhibitory effect of amylin on glucose-induced insulin secretion was confirmed by lowering the amylin concentration (500 nM) and increasing the glucose stimulus (11 mM); again, no effect of amylin on glucagon release was observed. Finally, amylin, at 500 nM, reduced the insulin response to 3.5 mM arginine (ca. 40%, P less than 0.025) without modifying the secretion of glucagon elicited by this amino acid. It can be concluded that, in the rat pancreas, the inhibitory effect of homologous amylin on unstimulated insulin secretion, as well as on the insulin responses to metabolic substrates (glucose and arginine), favours the concept of this novel peptide as a potential diabetogenic agent. PMID- 2270317 TI - Metabolic clearance rates of oxyntomodulin and glucagon in the rat: contribution of the kidney. AB - The half-life (t1/2) and metabolic clearance rate (MCR) of exogenous natural porcine oxyntomodulin (porcine OXM) and the synthetic analog of rat oxyntomodulin, [Nle27]-OXM (rat OXM), were compared with that of glucagon in control, sham-operated and acutely nephrectomized rats using the primed continuous infusion technique. The half-disappearance times for porcine OXM (8.2 +/- 0.5 min) and rat OXM (6.4 +/- 0.5 min) were 3-fold slower than that of glucagon (1.9 +/- 0.1 min). Acute bilateral nephrectomy significantly prolonged the half-disappearance time of rat OXM (8.2 +/- 0.7 min) and glucagon (3.6 +/- 0.4 min) compared with that of sham-operated animals (6.5 +/- 0.8 min and 2.5 +/- 0.2 min, respectively). The mean MCRs were similar for porcine and rat OXM (11.3 +/- 0.7 and 11.9 +/- 0.5 ml.kg-1.min-1) but were 3 times lower than that measured with glucagon (36 +/- 5 ml.kg-1.min-1). Bilateral nephrectomy reduced the MCR of OXM and glucagon by 38% and 34%, respectively. No significant increase in C terminal glucagon immunoreactivity was noticed during infusion of either porcine or rat OXM, measured directly in plasma, with a specific C-terminal glucagon antiserum or after HPLC. In the course of the glucagon infusion, blood glucose was increased 2-fold, while the same dose of porcine OXM or of rat OXM induced only a small increase over the values in phosphate buffer-infused rats. 10 times higher doses of rat OXM were necessary to obtain a similar hyperglycemic effect. These results indicate that: (1) the metabolism of OXM is 3-fold slower than that of glucagon, (2) renal clearance contributed close to 35% of the overall metabolic plasma extraction for OXM and glucagon and (3) OXM, although effective at a higher dose, when compared with glucagon, displays a hyperglycemic effect probably through the glucagon receptors. PMID- 2270318 TI - Insulin-induced hypoglycemia, L-dopa and arginine stimulate GH secretion through different mechanisms in man. AB - We sought to clarify the mechanisms of growth hormone (GH) secretion induced by insulin hypoglycemia, L-dopa, and arginine in man. The secretion of GH as measured by increased plasma level, in response to oral administration of 500 mg L-dopa or 30 min-infusion of arginine, was not modified by prior intravenous administration of 200 micrograms GH-releasing hormone (GHRH). It was, however, completely blocked by preadministered 50 micrograms SMS201-995, a long-acting somatostatin (SRIH) analog. GH release with 200 micrograms GHRH was completely blocked by 100 micrograms SMS201-995. GH secretion caused by insulin-induced hypoglycemia was significantly reduced but still present after administration of 100 micrograms of the analog. These results suggest that a suppression of SRIH release may be partially involved in the stimulatory mechanism of GH secretion by L-dopa. Coadministration of GHRH accentuated the stimulatory effect of arginine on GH secretion. Arginine significantly raised plasma TSH levels. These findings suggest that arginine suppresses SRIH release from the hypothalamus to cause GH secretion because SRIH suppresses TSH secretion. It is also suggested that some factor (or factors) other than GHRH and SRIH are involved in the mechanism by which insulin-induced hypoglycemia stimulates GH secretion, because the effect of insulin was not fully blocked in the presence of SRIH analog. Thus all the tests for GH release appear to act via different mechanisms. PMID- 2270319 TI - Teaching self-help skills to autistic and mentally retarded children. AB - Three autistic, mentally retarded children, ranging in age from 4 to 11 years, and a six-year-old mentally retarded girl, were taught various adaptive behaviors using a multiple baseline design. Skills taught were shoe typing, toothbrushing, hair combing, putting on pants, shirt, and socks, and eating and drinking. Training included modeling, verbal instructions, prompting, and edible and social reinforcement. Treatment procedures involved the whole-task method of teaching self-help skills and consisted of three phases: (a) the trainer modeled and verbally described the target behavior; (b) the trainer physically and verbally guided the child through the entire sequence of task-analyzed steps; and, (c) the child was instructed to perform the behavior independently. The results of this study and their implications for future research are discussed. PMID- 2270320 TI - Correspondence training: review and current issues. AB - This article reviews the literature on correspondence training and discusses issues of theoretical, conceptual, or applied importance. Generalization, maintenance, and application to mentally retarded individuals are addressed. The relationship between correspondence training procedures and the concept of self control is discussed. Directions for future research are described. PMID- 2270321 TI - A comparison of the Task Demonstration Model and the Standard Prompting Hierarchy in teaching word identification to persons with moderate retardation. AB - Six persons with moderate mental retardation were taught to identify three words by each of two different procedures. One, the Task Demonstration Model, was a fading procedure which relied on presenting many examples of both the correct and incorrect words while systematically increasing their similarity. The other, the Standard Prompting Hierarchy, is one of the most common procedures for teaching persons with mental retardation, and relied on a least-to-most intrusive prompting hierarchy. Data were presented in three phases and show that the Task Demonstration Model produced fewer errors in (a) acquisition (4% to 14%), (b) generalization (9% to 14%), and (c) maintenance (8% to 14%). Results were discussed in terms of the fading procedure and how the Task Demonstration Model provides a simple means for teachers to improve their students' responding in acquisition, generalization, and maintenance. PMID- 2270322 TI - Interactive graphics for the Macintosh: software review of FlexiGraphs. AB - While this product is clearly unique, its usefulness to individuals outside small business environments is somewhat limited. FlexiGraphs is, however, a reasonable first attempt to design a microcomputer software package that controls data through interactive editing within a graph. Although the graphics capabilities of mainframe programs such as MINITAB (Ryan, Joiner, & Ryan, 1981) and the graphic manipulations available through exploratory data analysis (e.g., Velleman & Hoaglin, 1981) will not be surpassed anytime soon by this program, a researcher may want to add this program to a software library containing other Macintosh statistics, drawing, and graphics programs if only to obtain the easy-to-obtain curve fitting and line smoothing options. I welcome the opportunity to review the enhanced "scientific" version of FlexiGraphs that the author of the program indicates is currently under development. An MS-DOS version of the program should be available within the year. PMID- 2270323 TI - [The significance and assessment of residual masses in lymphomas in remission]. PMID- 2270324 TI - [The continuous recording of ambulatory arterial pressure. The value of monitoring 4-hour subperiods]. AB - The ambulatory continuous arterial pressure monitoring permits a more exact definition of the degree of arterial hypertension. A ACMPA was performed in 86 subjects, 64 hypertensive and 22 normotensive controls during a daytime period of 16 hour with a noninvasive device. The results were compared to those obtained in the four four-hour subperiods. The correlation of each subperiod with the global studied period was: r = 0.915; subperiod 16-19 hours, r = 0.933; subperiod 20-23 hours, r = 0.924. It was observed that in any four-hour subperiod was quite similar to the mean value of the whole period. We conclude that in those cases in which it is not possible to perform a 24 hour ACMAP or during the whole daytime, a short four-hour monitoring is valid. PMID- 2270325 TI - [The relationships between cholesterol and arterial pressure in the Malaga-86 study. Something more than a casual association?]. AB - The frequent association of this vascular risk factors implies not just a potentiation of the vascular risk, but also the need for a wider therapeutical approach on this patients not only regarding the control of the arterial hypertension but also other risk factors. After a cross-sectional study of the prevalence of various vascular risk factors in the province of Malaga (Spain), we analysed the results as for the cholesterolemia and blood pressure in normotensives and hypertensives. In the hypertensive population we observed a tendency to present a higher levels of cholesterol as well as a higher prevalence of hypercholesterolemia (p less than 0.001); on the other hand, hypercholesterolemic people versus normocholesterolemics showed similar data related to their blood pressure and prevalence of hypertension. Finally we discussed the likely etiopathogenetic interrelationships between both vascular risk factors. PMID- 2270326 TI - [Spontaneous pneumomediastinum in adults]. AB - Pneumomediastinum cases admitted to our Respiratory Intensive Care Unit during the past 15 years are reviewed. After excluding secondary and iatrogenic pneumomediastinum, spontaneous pneumomediastinum was diagnosed in seven patients being all of them males. The causative conditions were status asthmaticus in four patients, intense cough in two and Valsalva manoeuver in one patient. The most frequent symptoms were dyspnea, chest pain and odynophagia. Subcutaneous emphysema appeared in six patients and there was associated pneumothorax in two cases. ECG was normal in six patients. All cases of spontaneous pneumomediastinum had a satisfactory evolution with conservative treatment resolving in four to eight days. PMID- 2270327 TI - [The importance of English as a vehicle of communication and scientific information and its teaching in the health sciences]. PMID- 2270328 TI - [Reflections on information management in clinical research]. AB - Some considerations are made on the importance of clinical, information and its transcendence in medical research, as well as on the ethical value of a qualitatively correct data treatment. After describing by means of a bibliographical search, the present-day tendency towards knowledge based systems, there is offered a general overview of clinical information management, from data collection through study design and statistical assessment, up to the building of a knowledge data base. PMID- 2270329 TI - [Apoprotein E phenotypes. A study of the population of Malaga]. AB - The distribution of apoprotein E phenotypes in a randomly chosen population sample of Malaga was compared to other published studies performed in other countries, observing minimal differences in Caucasian populations but significant differences with oriental ethnic groups. Cholesterol and triglyceride plasma levels were not significantly different in the different apo E phenotypes. A high proportion of subjects (26%) with hydrocarbon metabolism abnormalities (diabetic and glucose intolerant) was observed in phenotype E4/3 and very low (4.7%) in phenotype E3/2. The study of plasma triglyceride levels which were higher in the diabetic group, revealed a greater increase in phenotype E4/3 than in E3/3. These results support the idea about the complex relationship that exists between apo E phenotypes and some cardiovascular risk factors. PMID- 2270330 TI - [The nonsurgical treatment of biliary lithiasis]. PMID- 2270331 TI - [Bacterial resistance in extrahospital urinary infections]. PMID- 2270332 TI - [Thrombotic thrombocytopenic purpura in a patient with the acquired immunodeficiency syndrome]. PMID- 2270333 TI - [Infection by the human immunodeficiency virus and Hodgkin's disease]. PMID- 2270334 TI - [Acute diarrhea. Care in a general hospital]. PMID- 2270335 TI - [Pleural Kaposi's sarcoma. Its intravital diagnosis by pleural biopsy]. PMID- 2270336 TI - [Fibrositis as the form of presentation of a nonsecreting myeloma]. PMID- 2270337 TI - [Acute rhabdomyolysis. A study of 44 cases]. AB - Fourty four patients suffering non traumatic rhabdomyolysis (RM) are studied. The most frequently encountered etiologies were neurologic abnormalities in 26 patients, followed by infections in 7 patients and metabolic abnormalities in four cases. Eleven patients (25%) presented several associated factors. The clinical manifestations of RM were not very significant, with only 18% of patients presenting muscle pain, 38.6% proteinuria and 36.4% hematuria. A significant increase in K, CPK, LDH, and ASAT values was observed after the RM episode (p less than 0.05). Those patients with an infectious RM were older (p less than 0.05) and presented higher urea (p less than 0.01) and creatinine (p less than 0.05) values. Only two patients presented renal failure. One patient with septic shock died. RM is a relatively common condition, often secondary to multiple systemic processes, which can go unnoticed due to the underlying disease. PMID- 2270338 TI - [The Revue des Maladies Respiratoires. A French language review: why and how?]. PMID- 2270339 TI - [Respiratory manifestations of HIV infections in children]. AB - Respiratory disorders during the course of infections in children who are HIV positive are frequent. These are interstitial pneumonia (IP) and bacterial pneumonia. The acute IP are most often infectious in particular opportunist infection, and are dominated by Pneumocystis carinii (PC, 82 to 86% of the infectious agents isolated). This is often a presenting feature of an HIV infection and the radiological picture is very variable and the diagnosis rests on bronchoalveolar lavage which is readily achievable even in the infant. The immediate outcome is usually favourable and cotrimoxazole is efficacious and well tolerated. However pneumonia to PC points to a poor prognosis because they are always associated with a profound deficit or cellular immunity. All these criteria are against the likelihood of lymphoid PI which is, however, much more frequent in children than in adults. It is the chronic interstitial pneumonia with a "large grain" miliary radiological pattern and preserved cellular immunity and the absence of opportunistic infections in particular PC pneumonia. In addition, beyond the absence of PC, the bronchoalveolar lavage liquid shows a constant hyperlymphocytosis without polymorphonuclear leucocytes which is significantly different from that which is observed during the course of PC pneumonia. The long term prognosis of chronic PI, however, remains guarded with the possibility of seeing a worsening of the immune function. As for bacterial pneumonias they usually present as an acute lobar pneumonia with a banal organism but severe gram negative pneumonias are possible justifying a detailed systematic approach in certain cases. PMID- 2270340 TI - [Clinical management by the respiratory physician of patients with HIV infections]. AB - The lung is directly affected by HIV virus early in the disease and is the site of a specific lymphocytic alveolitis. Neoplastic pulmonary disease linked to the virus occurs (Kaposi sarcoma, lymphoma and epidermoid tumour) but it is principally following opportunistic infections that patients with AIDS come under the care of a respiratory physician. Certain of the responsible infectious agents causing opportunistic pneumonia are probably present in a latent fashion before the disease presents and are reactivated by the immuno-depression. They may occur successively such as tuberculosis, toxoplasmosis (in this case pulmonary), infection to CMV and pneumocystis. Other infectious agents are transported by the environment and lead to recurrent bacterial infections, mycotic infections or infections with atypical mycobacteria. The clinical management of these different diseases has advanced greatly from a diagnostic therapeutic prophylactic and curative viewpoint. PMID- 2270341 TI - [Techniques involved in the protection of the lung and heart-lung for the purpose of transplantation]. AB - Impaired healing of the bronchial anastomosis and its subsequent complications has been an important problem following lung transplantation. The decrease in the dosage of steroids, the use of cyclosporine immunosuppressive therapy and the use of an omental flap to revascularize rapidly the bronchial anastomosis, have reduced considerably the incidence of these post-operative bronchial complications. We have recently demonstrated that the application of a pedicled intercostal muscle graft or peritracheal membrane adipose tissue wrap on the bronchial anastomosis improved bronchial healing by restoring a vascular flow across the anastomosis within 7 days after left lung allotransplantation. Since the introduction of heart-lung transplantation at Stanford (USA) in 1981 and Pittsburgh in 1982 for the treatment of Eisenmenger's syndrome and terminal pulmonary vascular diseases, more than 250 combined heart-lung transplantations have been carried out throughout the world. However the present intermediate and long term results obtained with this operation have not yet reached the same level of success as cardiac transplantation alone. While several factors such as selection of candidates and donors have played a role in this difference, a prominent cause has been the lack of a reliable and simple method for pulmonary protection against prolonged ischemia. Most of the techniques proposed against ischemia can be classified as normothermic or static hypothermic cardiopulmonary preservation. The utilization of the normothermic method has not always been successful. For this reason, interest has now been directed towards the potential for hypothermic preservation of the heart-lung bloc and the use of free radical scavenger therapy in the reduction of reperfusion injury. PMID- 2270342 TI - [From the parenchyma to the mucosa biopsy: significance and importance of local assays of antibiotics. A critical study]. AB - The authors discussed the relevance of antibiotic concentrations as measured in tissues and fluids of the respiratory tract. They analysed theoretical factors which influence tissue distribution of antibiotics as well as the results of studies carried out in animal and in human tissues. Various factors may interfere with the results of antibiotic assays: but the data published by various groups were usually convergent: this confirms the significance of "tissue pharmacokinetics". New protocols based on more refined and reliable techniques were proposed recently, which underlines the attention payed to these studies. PMID- 2270343 TI - [Plasma histamine and exercise-induced bronchospasm]. AB - The pathogenesis of bronchospasm of effort is not yet elucidated and it is probable that is determined by multiple factors. In this study we have tested the role of mastocytes in taking as an index of their activation the fluctuation of plasma histamine levels during repeated exercise tests. We will show that asthmatic subjects who develop bronchospasm on effort have a significant rise (times 3) in their level of serum histamine whilst normal subjects don't show much change. Furthermore in a repeated effort test we have observed a strict parallelism between the occurrence of bronchospasm of effort and a rise in plasma histamine levels. These different observations enable us to consider that the activation of mastocytes and the liberation of mediators which follow play an important role in the pathogenesis of bronchospasm of effort. PMID- 2270344 TI - [Asthma and air pollution. A study of admissions to the Hospital of Saint Nazaire]. AB - To test the possible influence of atmospheric pollution on the frequency of asthmatic exacerbations we have looked to see whether there is a link between the number of daily admissions for asthma in hospitals in Saint-Nazaire and data from pollution sensors in the network of the Association for the Measurement of Atmospheric Pollution in the Loire estuary. The pollutions studied were sulphur dioxide, oxide of nitrogen (NOx) and non sedimenting dust (black smoke). The meteorological data (speed and direction of the wind and temperature) were also recorded. The study was carried out for 18 months in a retrospective fashion. During this period 372 hospital admissions were recorded in 229 subjects. The number of daily admissions correlated in a significant fashion with the level of black smoke (r = 0.149, p less than 0.001) and this result was particularly due to subjects who were less than 15 years old. In this group the frequency of hospital admission was doubled on those days when the level of smoke was at its most elevated. There was a weak link between the peaks of SO2 (r = 0.116, p less than 0.05). An analysis of the place of residence in those hospitals and the dominant direction of the wind did not enable us to confirm the role of the principal sources of industrial pollution, which were all situated to the east of Saint-Nazaire. PMID- 2270345 TI - [Scintigraphic assessment of pulmonary deposition of pentamidine administered by aerosol]. AB - Isotopic techniques enable to determine the best conditions to aerosolize pentamidine as a preventive treatment of pneumocystis. An original labelling technique of pentamidine isethionate has led into a feasibility study of pentamidine scintigraphy in the monkey, and then to a clinical study. A tracer dose of 2 mg of pentamidine isethionate was diluted into 200 mg of pentamidine mesylate. An ultrasonic nebulizer (TV 6000) and a jet nebulizer (Venticis II) were first compared in four baboons. With the two nebulisers the curves of pulmonary kinetic activity showed a peak 10-15 minutes after the beginning of inhalation and then a plateau. With the ultrasonic TV6000 the pulmonary dose was on average 0.8 mg or 0.4% of the pentamidine aerosolized and the gastric contamination 3.1%. With the Venticis II compressed air apparatus the amount of pentamidine delivered to the deep lung was a mean of 4.2 mg or 2.1% of the aerosolized dose whereas the gastric contamination was only 0.5%. The delivery of the aerosol by the ultrasonic inhaler TV 6000 was then compared with two compressed air inhalers Venticis II and Respirgard II in four patients infected with HIV virus who were submitted to a preventative therapy against pneumocystis. With the ultrasonic TV 6000 the pulmonary dose was 0.8 mg or 0.3%-0.5% of the dose of pentamidine aerosolized and the digestive contamination was 3.1%. The performance of the two compressed air nebulizers Venticis II and Respirgard II were similar. The amount of pentamidine delivered to the deep lung was respectively 12 and 14 mg or 6 and 8% of the dose of pentamidine aerosolized and the digestive activity was 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270346 TI - [Echography of pneumothorax]. AB - Ultrasound of 28 radiologically confirmed cases of pneumothorax were compared to 100 controls. Specific ultrasonographic signs were shown in all cases and could be categorised into four groups: isolated pneumothorax (n = 16), hydro pneumothorax (n = 9), subcutaneous emphysema (n = 1) and post aspiration pneumothorax (n = 2). The isolated pneumothorax was characterised by the disappearance of the lung deflection signal. The effusion of the hydropneumothorax allows in addition a curtain sign which depicts the movement of the air/fluid level, the detachment of the lung being calculated across the liquid window whose echo-structure is analysed. Pneumothoraces appearing during an echo guided thoracic puncture are confirmed by the disappearance of the pathological image. Thus echography appears to be a new method in the diagnosis of pneumothoraces and is complimentary to standard radiology. It should be confirmed as particularly useful during the process of thoracic puncture or juxta diaphragmatic puncture when following the process of a pneumothorax, for emergency situations and/or those in which no radiological equipment is available. PMID- 2270347 TI - [Effects of individualized aerobic training in the readaptation of the asthmatic child to exercise]. AB - There have been few works studying the effects of training in asthmatics and there does not yet exist any study utilising the idea of the individualization of training. This is why the aim of this study was to assess the value of the effects of individualised aerobic training on cardio-respiratory aptitude in the asthmatic child. This study was carried out on two populations of asthmatics, swimmers and non-swimmers matched for age, height, degree of bronchial obstruction during a remission and baseline of physical fitness. Each child in the swimming group was trained to a metabolic level corresponding to the ventilatory threshold. After a period of 3 months a second cardio-respiratory evaluation was carried out. A clear cut improvement (20%) of VO2 max was observed as well as a proportional elevation of the ventilatory threshold in the swimming group. The VE max, the VT max, the VT/Timax, the FC max and the maximal oxygen uptake were also recorded. On the other hand aerobic training seems to be without effect on resting pulmonary function, even if the clinical state of the children improved. In conclusion this study shows that aerobic training closely adapted to the level of each child, obtains an important and rapid gain in cardio respiratory fitness which leads to a better exercise adaptation. In addition the progression of the ventilatory threshold implies an increased capacity for work without the appearance of hyperventilation. This enables an understanding of how aerobic training is generally accompanied in the asthmatic with a better respiratory comfort and argues in favour of the perfect efficacy of this type of reconditioning in the re-adaptation to effort in these patients. PMID- 2270348 TI - [Pulmonary tuberculosis secondary to fistulization of Pott's abscess. A case report]. AB - The authors report a case of pulmonary tuberculosis appearing after an endobronchial fistula from a Pott's abscess. Such a clinical presentation is rare even in a developing country (PVD), where there is experience of more than 200 cases of tuberculous spondylodiscitis seen over a period of six years. The frequency of paravertebral abscess during the course of Pott's disease is around 52%, in the thoracic lesion their exteriorization by endobronchial fistula is around 4% (5 out of 114). The outcome is generally more simple and here a cure was achieved after six months of chemotherapy. PMID- 2270349 TI - [Histiocytosis X: excavated macronodular form. Initial alveolar phase with spontaneous regression. Role of smoking]. AB - This is a case report of a 39 year old patient in whom histiocytosis X was discovered following a cough which had appeared several months before. The radiological investigations were distinctive immediately associating the alveolar lesions and the excavated macronodules. The clinical examination was normal but there were some laboratory features suggesting inflammation. The diagnosis was achieved following a surgical biopsy which on histological examination showed histiocytic granulomas and the immunology revealed cells which were positive for OK T6 monoclonal antibodies and S100 antiprotein antibodies. There was subsequently a spontaneous regression with disappearance of the nodular shadows only leaving a few cystic forms. This observation is distinctive and is characterised by the rare appearance of the initial radiology and also confirms the predisposing factor of smoking in the pathogenesis of histiocytosis X. PMID- 2270350 TI - [Primary malignant melanoma of the trachea. Apropos of a case]. AB - Primary malignant melanoma of the lower airways is very rare. 24 cases have been collected over the past century. Our case was a patient of 52 years of age who had been discovered to have a tracheal tumour which was found to be a malignant melanoma and was treated with a Laser. The major problem is to establish that the tumour is primary. The combination of clinical evidence, paraclinical, subsequent outcome and in certain cases the autopsy enables the diagnosis of a primary tumour to be retained without having absolute certainty because a cutaneous melanoma can disappear after having metastasised. PMID- 2270351 TI - [Pleurisy in ovarian hyperstimulation syndrome. Apropos of a case]. AB - The syndrome of ovarian hyperstimulation is a little known aetiology of pleural effusion. It should be thought of in young women who are under treatment to induce ovulation. Serous effusions which occur in these cases are a serious sign. The effusions are exudates and not transudates as occurs in Demons-Meigs syndrome. The treatment which will be undertaken ought to consider the possibility that a pregnancy is underway. PMID- 2270352 TI - [Bronchiolitis obliterans, pneumocystosis and HIV infection]. AB - A 39 year old man who was HIV positive and was treated with trimethoprim sulfamethoxazole for pneumocystis with hypoxaemia. During the acute episode he had a persistent fever of 38 degrees and hypoxaemia with a PaO2 of 65 mm/Hg and bilateral opacities both radiologically and on a CT scan, which were of alveolar type, with bronchograms identical to those observed before the treatment of the pneumocystis. In view of the negative evidence for a respiratory or extra respiratory infection, a surgical biopsy was performed and this revealed lesions of bronchiolitis obliterans with an organising pneumonia (BOOP). After the thoracotomy, there was a spontaneous clinical cure in a few days and radiological clearance in a month. This very rare diagnosis should be added to the list of causes of alveolar pneumopathy with infiltration and fever occurring during the course of an HIV infection. PMID- 2270353 TI - [Endobronchial aspergillosis associated with a carcinoid tumor]. AB - We report a case of a 62 year old man who presented with effort dyspnoea accompanied by a cough and haemoptysis. The chest radiograph of the thorax showed atelectasis of the right upper lobe. Bronchoscopy showed evidence of a tumour like mass obstructing the right bronchus and this revealed itself to be a mass of organised fibrinous deposit in granulation tissue containing numerous colonies of Aspergillus. In fact it appeared to be an obstructive Aspergillus bronchitis, with a pseudo-tumour appearance attached to a carcinoid tumour which was obstructing the apical segment of the right upper lobe. Obstructive Aspergillus bronchitis makes up only a small percentage of overall respiratory disease caused by Aspergillus. They pose a problem of differential diagnosis with bronchopulmonary aspergillosis which is much more frequent. PMID- 2270354 TI - [Asymptomatic miliary calcifications in a 32-year-old woman]. PMID- 2270355 TI - [The Revue des Maladies Respiratoires]. PMID- 2270356 TI - Effects of hypoxia on capillary orientation in anterior tibialis muscle of highly active mice. AB - The plasticity of capillary orientation in response to combined hypoxic hypoxia and high activity levels was investigated in anterior tibialis muscle of Japanese waltzing mice (Mus wagneri rotans). Following 2 weeks of normobaric, normothermic hypoxia (PIO2 congruent to 87 Torr), muscles were perfusion-fixed in situ with glutaraldehyde and analyzed morphometrically. Muscles from hypoxic waltzers, HW, were compared with those from normoxic waltzers, NW, and normoxic control mice, N. At sarcomere lengths from 2.84 to 1.69 microns, tortuosity and branching increased capillary length 3 to 38%. When capillary orientation was related to sarcomere length, muscles from HW were not different from NW or N. At group averaged sarcomere lengths of 2.22 microns (HW), 2.33 microns (NW) and 2.35 microns (N), tortuosity and branching contributed 16,20 and 18% respectively, to capillary length. We conclude that high activity levels under normoxic or hypoxic conditions in Japanese waltzing mice do not augment muscle capillary length by means of increased capillary tortuosity and/or branching. PMID- 2270357 TI - Gas mixing in dog lungs during high frequency ventilation studied by partial washout-single exhalation technique. AB - Gas mixing was studied in 10 anesthetized paralyzed dogs during high-frequency low tidal ventilation (HFV). After simultaneous washin of ethane (1%) and washout of resident argon (0.9%) the gas inflow was switched to atmospheric air for varied time intervals leading to varied levels of C2H6 washout and Ar washin. After the stop of HFV at predetermined test gas washout/washin levels, a constant flow exhalation by a servo ventilator was performed and expirograms of C2H6 and Ar were recorded. Measurements were performed at varied ventilation frequencies (10-40 Hz), stroke volumes (20-40 ml), lung volumes (730-830 ml), expiratory flow rates (0.1-0.01 L/sec), breath-holding prior to exhalation (0-12 sec) and test gas washout levels achieved by varying the washout time (1 to 65 sec) before onset of exhalation. The expirograms showed a close to linearly rising alveolar plateau. They were analyzed for series dead space and alveolar slope which was normalized to the initial-to-final partial pressure difference. The normalized slopes of C2H6 washout and Ar washin were averaged, whereby the effect of shrinking lung volume due to continuing CO2/O2 exchange at low R was assumed to be suppressed. The slope was little affected by changes of stroke volume, decreased slightly with increasing frequency, and decreased considerably with breath-holding or increasing lung volume. As washout progressed, the alveolar slope first increased, attained a maximum at about half-washout and thereafter decreased. The finite values of the alveolar slope indicated that intrapulmonary gas mixing during HFV was incomplete. The slopes were larger than expected from diffusion calculations on symmetrically branching lung models. The behavior of the slope at varied washout levels suggested involvement of parallel ventilation/volume inhomogeneity coupled with sequential emptying. PMID- 2270358 TI - Effect of dichloroacetate on ventilatory response to sustained hypoxia in normal adults. AB - In adult humans, the ventilatory response to acute sustained hypoxia is biphasic, characterized by an initial brisk increase followed by a decline to an intermediate plateau. Recently, it has been shown that hypoxic lactate formation in the brain depresses ventilation in peripherally chemodenervated animals, and postulated that this formation might mediate the hypoxic ventilatory decline observed in adult humans. To investigate this hypothesis, the ventilatory response to 25 min of acute isocapnic hypoxia (SaO2 = 80%) was evaluated in adult humans after pretreatment with intravenous dichloroacetate (DCA), a drug that crosses the blood-brain barrier and reduces lactate formation. Ten subjects were pretreated with DCA (50 mg.kg-1.h-1) or normal saline infusion on two days in a double blind manner. The infusion started 35 min before the institution of hypoxia and continued throughout the experiment. Independent of pretreatment, the ventilatory response to acute sustained hypoxia was biphasic; an increase followed by a decline. Ventilation during hypoxia declined significantly and the magnitude of the decline did not differ between the DCA and placebo pretreatments, averaging 3.32 +/- 0.45 and 3.17 +/- 0.58 L/min, respectively (mean +/- SE). With and without DCA infusion the hypoxic ventilatory decline was due to significant decrease in tidal volume and mean inspiratory flow without changes in breathing frequency. We conclude that brain lactic acidosis is unlikely to be involved in the ventilatory response to sustained hypoxia of adult humans, at least in the range of hypoxia studied. PMID- 2270359 TI - The influence of carotid body chemoreceptors on expiratory muscle activity. AB - Respiratory muscle EMG responses to transient, specific carotid body excitation (NaCN, hypoxia) and inhibition (dopamine, hyperoxia) were studied in 7 unanesthetized standing dogs while intact (N = 7) and during bilateral cold block of the vagi (N = 3). In all dogs carotid body excitation augmented the EMG activities of both expiratory muscles (triangularis sterni, TS; transversus abdominis, TA) and the (inspiratory) crural diaphragm (CR); carotid body inhibition significantly reduced phasic EMG activities in all muscles. With vagal blockade the response of the TS to carotid body stimulation was increased; that of the TA was essentially unchanged from the intact state. In all dogs expiratory muscle recruitment in response to carotid body excitation/inhibition could either precede or follow that of the CR. We conclude that in response to specific, transient carotid body excitation or inhibition: (1) Changes in CR, TS and TA EMGs are qualitatively similar. (2) Vagal feedback is strongly inhibitory to TS and excitatory to TA. (3) Changes in expiratory muscle EMGs do not require preceding changes in the CR. Carotid body stimulation contributes significantly to the generation of phasic expiratory activity during eupnea. PMID- 2270360 TI - Gas transport enhancement in high-frequency oscillation. AB - Gas transport during high-frequency oscillation (HFO) with (HFO+BT) and without bias tube (HFO-BT) was investigated in 10 anesthetized supine dogs. The oscillatory volume effectively delivered to the lungs, airway occlusion pressure and lung volume above functional residual capacity (FRC), regulated by a newly deviced pressure control system, as well as the oscillatory frequency (20 Hz) were adjusted to equal levels in HFO+BT and HFO-BT. At a fresh gas flow rate (fgf) of 3 L/min (room air), arterial CO2 partial pressures (PaCO2) decreased from 49.9 +/- 6.5 mm Hg (mean +/- SD) to 40.2 +/- 6.3 mm Hg (P less than 0.01) i.e. by 19.2 +/- 8.7%, and arterial O2 partial pressures (PaO2) increased from 71.5 +/- 13.1 mm Hg to 85.6 +/- 14.6 mm Hg (P less than 0.01) or by 20.5 +/- 12.0% in HFO-BT as compared to HFO+BT. At a fgf of 6 L/min, PaCO2 decreased less but still significantly (P less than 0.025) from 42.1 +/- 6.5 mm Hg to 37.8 +/- 6.8 mm Hg (10.4 +/- 5.6%) and PaO2 increased from 78.1 +/- 12.9 mm Hg to 84.6 +/- 16.4 mm Hg i.e. by 8.1 +/- 6.4% (P less than 0.05) in HFO-BT. The higher gas transport efficiency after removing the bias tube can be explained by two mechanisms: (1) By removing the bias tube, the volume of the bias system decreased from 54 ml in HFO+BT to 1 ml in HFO-BT and rebreathing of exhaust gas from the bias system is therefore eliminated in HFO-BT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270361 TI - Hyperinflation and expiratory muscle recruitment during NREM sleep in humans. AB - The purpose of this study was to determine the effect of hyperinflation on expiratory muscle recruitment during NREM sleep in healthy humans. Hyperinflation was produced by negative pressure in a tank ventilator or application of positive end-expiratory pressure (PEEP). Expiratory and inspiratory electromyograms (EMGexp and EMGinsp) were measured using transcutaneously implanted wire and surface electrodes, respectively. During wakefulness, sustained hyperinflation (3 5 min, +0.72 +/- 0.31 L) in the tank respirator caused augmentation of EMGexp (+77%, P less than 0.05) and EMGinsp (+27%, P less than 0.05) in all subjects. Brief hyperinflation with PEEP (5 breaths, +0.53 +/- 0.32 L) augmented EMGexp in 3 of 6 subjects and EMGinsp in 5 of 5 subjects (+98%, P less than 0.05). During NREM sleep, sustained hyperinflation (+0.54 +/- 0.17 L) in the tank respirator caused no change in EMGexp and a small increase in EMGinsp (+9%, P less than 0.001). Brief hyperinflation with PEEP (0.29 +/- 0.10 L) caused no change in EMGexp or EMGinsp. Sustained hyperinflation with PEEP activated EMGexp only in subjects whose end-tidal CO2 increased. We concluded that moderate hyperinflation does not recruit expiratory muscles during NREM sleep as it does during wakefulness. PMID- 2270362 TI - The drainage routes of the bronchial blood flow in anesthetized dogs. AB - It is generally accepted that the bronchial blood flow from extrapulmonary airways drains to the systemic veins through the bronchial veins, while that from the intrapulmonary airways drains into the pulmonary vasculature and eventually the left heart. This concept has not been confirmed by physiologic studies in live animals. We measured the routes taken by radionuclide-labeled Diethylenetriamine pentaacetate (DTPA) deposited in the extrapulmonary and the intrapulmonary airways in dogs. In living, anesthetized open chest animals, the pulmonary circulation of the left lower lobe was isolated and perfused with autologous heparinized blood. 99mTc DTPA was deposited on the mucosa of the extrapulmonary left mainstem bronchus just beyond the main carina (extrapulmonary deposition) and 111In DTPA on that of an intrapulmonary left lower lobe segmental bronchus (intrapulmonary deposition). Sequential blood samples from the right heart and from the isolated left lower lobe pulmonary circuit were counted for radioactivity, corrected for the volume in which they were distributed and for the bronchial blood that flowed into the isolated left lower lobe circuit, and expressed as the ratio of systemic to pulmonary drainage from each deposition site. The extrapulmonary tracer drained mostly to the systemic veins (84% of total) but also into the pulmonary circulation (16% of total). The intrapulmonary tracer drained mostly into the pulmonary circulation (70% of total) but also into the right heart (30% of total). Since tracers from both deposition sites drained to both circulations, the bronchial vasculature is continuous between the systemic (right heart) and the pulmonary circulation. Thus, it may provide a pathway for blood flow between the right and left heart. PMID- 2270363 TI - Flow distribution in a single bifurcation during high-frequency oscillation. AB - The distribution of flow in a single bifurcation was studied to examine what factors played a critical role. Flow was preferentially directed down the straightest pathway when higher frequencies and/or larger tidal volumes were used, but otherwise followed the pattern dictated by the distal impedance regardless of bifurcation geometry. In a symmetrical model, the observed flow distribution was in good agreement with a mathematical prediction based on linear impedance theory, though this was not the case when tidal volumes were increased. The difference in mean pressure between the two terminal units was also a strong function of branching angle and the Reynolds number. These findings suggest that the geometrical factors and local flow conditions contribute to both the flow and mean pressure distribution in an inertia-induced nonlinear manner. Consequently, linear impedance theory can be applied only to the limited situation of low tidal volume and symmetric configuration. PMID- 2270364 TI - [Identification of a focus of beta-thalassemia in Tamiahua, Veracruz]. AB - The prevalence of beta thalassemia (B-thal) in Mexico is largely unknown, and it is thought that the disease is confined to populations with Mediterranean ancestors. Various reports suggest that in certain parts of the coast in the Gulf of Mexico the prevalence of both B-thal and hemoglobin S disease/trait is high. We studied prospectively a town with 11,000 inhabitants named Tamiahua, located along the Gulf Coast, in the State of Veracruz, and very close to the State of Tamaulipas. A group of 200 inhabitants was initially studied: the prevalence of B thal was 15% and 6% of them had sickle cell trait. The prevalence of B-thal is the highest reported in the country. In a second part of the study, two family trees with members heterozygous for B-thal and/or Hb S trait were constructed. The ethnic characteristics of the studied population makes unlikely that the gene was derived from white Europeans but not from black Africans. Inasmuch as the indians living in that part of the country belong to the macro-maya glotochronological group, where a relatively high prevalence of B-thal has also been identified, we feel that it is possible that B-thal was present in our country before the Spaniards arrived to Mexico. PMID- 2270365 TI - [Prevalence of adenomatous and hyperplastic polyps of the colon in the population of the General Hospital of Mexico. An autopsy study]. AB - A prospective survey of 450 autopsies was conducted to determine the prevalence of colorectal dysplastic polyps in the population of the General Hospital of Mexico City. The colon and rectum were removed and examined for the presence of polypoid lesions; their size, location, and appearance were described. All of the lesions were examined and classified according to their microscopic diagnosis. Results revealed a single polypoid lesion in nine cases; four were classified as regenerative or inflammatory and five as dysplastic. Four of the latter were in females and one in a male; their mean age was 64 years. Macroscopically four were pedunculated and one sessil; all measured less than 0.6 cm; two were located in the transverse colon and three in the left colon. No hyperplastic polyps were found. After standardization for age, comparison with similar studies performed in other countries showed an extremely low prevalence rate for dysplastic colorectal polyps (2.7%) in our patient population, similar to one reported in Iran and higher than that found in the African Bantus, but it is one of the lowest when compared with European and US series. PMID- 2270366 TI - [Nodular lymphoid hyperplasia of the intestine. Clinico-pathologic characteristics in 11 cases]. AB - The clinical-pathological characteristics of 11 patients with intestinal nodular lymphoid hyperplasia (INLH) are described. Five fulfilled the criteria for Herman's syndrome and presented all or several of the following alterations: dysgammaglobulinemia, recurrent respiratory tract infections, sinusitis, pneumonia and giardiasis; of the remaining six cases, in five gammaglobulin levels were not quantified and in one they were normal. All the patients in this group suffered from recurrent pharyngotonsillitis, and Giardia lamblia was isolated in four. In both groups the INLH occurred in young patients with an average age of 21 years. Eight of the 11 were men. The most frequent symptoms included diarrhea, steatorrhea and weight loss. Radiologically, INLH usually was a finding affecting the jejunum and/or the ileum. Prominent lymph nodes in mucosa and submucosa were documented histologically in all cases, and a large decrease or absence of plasma cells in the lamina propria was seen in 7 of the 11. In spite of the diversity in the treatment schemes instituted, symptoms persisted for months or years after diagnosis. In two cases (one with dysgammaglobulinemia and one without) associated intestinal lymphoma existed. Other associated diseases included non-deforming joint arthritis, erythema nodosum, and intestinal infection by E. coli and Entamoeba histolytica. PMID- 2270367 TI - Hypoalbuminemia as a risk factor for amikacin nephrotoxicity. AB - Hypoalbuminemia has been recently informed by us as a risk factor in aminoglycoside nephrotoxicity. Since amikacin has a low serum binding capacity to albumin, the present study was designed to determine if the higher risk of amikacin nephrotoxicity in patients with hypoalbuminemia was due to low serum albumin per se or to malnutrition. One-hundred and thirteen ward patients who received endovenous amikacin for greater than 36 hours were studied prospectively. All were evaluated for the following factors: age, sex, diagnosis, serum creatinine, serum albumin, and nutritional status. They were followed with serum creatinine twice a week until cessation of therapy. Amikacin pharmacokinetics was studied in 11 subjects: 6 patients had a serum albumin less than 3.0 g/dL and 5 greater than 3.0 g/dL, but there were no differences in age, sex, weight, diagnosis, arterial pressure and nutritional status. The overall incidence of toxicity was 11%. In patients with serum albumin less than 3.0 g/dL it was 17.3% and in those greater than 3.0 g/dL it was 2.2%, p less than 0.05. There was no difference in the nutritional status between toxicity and non toxicity groups. In the pharmacokinetic study, the peak levels obtained one hour after amikacin administration were higher in patients with serum albumin less than 3.0 g/dL than in those with normal serum albumin (12.7 +/- 1.6 vs 9.0 +/- 1.2, p less than 0.002). In conclusion hypoalbuminemia is a risk factor in aminoglycoside nephrotoxicity regardless of the nutritional status. PMID- 2270368 TI - Pathophysiology of experimental nephrotic syndrome induced by puromicyn aminonucleoside in rats. III. Effect of captopril, an angiotensin converting enzyme inhibitor, on proteinuria and sodium retention. AB - The effect of the converting enzyme inhibitor (CEI) (captopril, 50 mg/kg/day) on proteinuria (UProt), urinary aldosterone (UAldoV), plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensinogen concentration (PAC), urinary sodium (UNaV), serum total protein, and body weight was studied for 21 days in an experimental nephrotic syndrome (NS) model induced in rats by a single injection (15 mg/100g) of puromycin aminonucleoside (PA). The effect of captopril on control rats without NS was also characterized. In control rats, captopril increased PRC and PRA, and decreased PAC; it had no effect on UNaV, UAldoV, UProt, total serum protein and body weight. In rats with NS, captopril had no effect on sodium retention, hypoproteinemia, and UProt; it abolished the increased UaldoV and favored weight loss. Captopril also rose PRA and PRC, and decreased PAC in PA-nephrotic rats; these changes were similar to those produced by captopril in control rats. The mortality rate was higher in nephrotic rats treated with captopril (37%) than in untreated nephrotic rats (13%). It is concluded that captopril has no beneficial effects on the course on NS induced by PA during the first 21 days, and supports the contention that sodium retention is not related to the renin-angiotensin-aldosterone system activity in these rats. PMID- 2270369 TI - Papillary cystic neoplasm of the pancreas. Two cases treated by surgery. AB - The papillary cystic neoplasm of the pancreas is a rare tumor. Two cases are presented, one of a 38-year-old man and the other of a 23 year-old woman. Both had mild upper abdominal symptoms and were successfully resected with a distal pancreatectomy. Forty-five well documented cases informed in the literature are reviewed. The neoplasm has a striking preference for young women and a relatively benign course with only 10% of the reported cases presenting recurrence or distant metastases. PMID- 2270370 TI - [Sphincteroplasty of the minor papilla in a female patient with pancreas divisum]. AB - We report the case of a 30 year old woman with recurrent episodes of acute pancreatitis secondary to pancreas divisum. The diagnosis was established 18 years after the initiation of her symptomatology. She denied a family history of pancreatic disease and had no risk factors in her personal history. Diagnosis was confirmed by endoscopic retrograde cholangiopancreatography. She was surgically treated by means of a sphincteroplasty of the minor papillae with excellent results. After three years of follow-up, the patient remains asymptomatic. PMID- 2270371 TI - [Hypercalcemia and osteolytic lesions associated with pre-B-cell primary lymphoma of the bone marrow. A case report]. AB - Primary bone marrow lymphomata are infrequent; most of them are of B-cell origin, and those of a T-cell lineage produce mainly both hypercalcemia and osteolytic lesions apparently due to abnormal production of osteoclast-activating factor. We report a 15-year old patient with a primary bone marrow lymphoma: 85% of his infiltrating malignant lymphocytes displayed cytoplasmic mu-chains compatible with a pre-B phenotype. The cells failed to display the CALLA/CD 10 antigen. Serum calcium was 7.5 mEq/L (range 4-5 mEq/L); the bone biopsy of an osteolytic lesion disclosed a large-cell, diffuse non-Hodgkin's lymphoma. No malignant cells were found in the peripheral blood and there were no enlarged lymph nodes. The patient was treated with 6 courses of chemotherapy: hydroxyldaunorubicin, vincristine and prednisone (HOP). Complete remission was achieved and the patient was placed on continuation chemotherapy with daily six-mercaptopurine and weekly methotrexate, together with HOP pulses every three months. The hypercalcemia disappeared together with the fever and the bone pain: the patient has been followed 6 months. Data on this case are discussed together with those previously published in regard to the low prevalence of bone lesions in primary B-cell lymphomas of the bone marrow, and to the similarity of this B-cell malignancy to others that produce both hypercalcemia and bone lesions, i.e. multiple myeloma. PMID- 2270372 TI - [Extracorporeal shockwave biliary lithotripsy. Physical basis and clinical application]. AB - Extracorporeal shock waves lithotripsy is a new procedure discovered and applied in the present decade to treat urinary and biliary stones. Shock waves are acoustic waves similar to sonic waves which follow the acoustic laws and therefore the shock waves can be refracted or reflected depending on the medium interface. Due to the high water content, the human body can be crossed by shock waves which eventually may be focused on the target stone. There are several commercially available shock waves generators, i.e. the spark gap emisors which were the first ones, and the piezoceramic and electromagnetic emisors. To focus the shock waves on a biliary stone the machines are provided with fluoroscopic or ultrasound devices or with both in the most advanced machines. Using an electromagnetic emisor (Lithostar plus) our group has treated 78 patients with biliary stones without analgesia or anesthesia. Total stone fragmentation was achieved in 85% of the cases. In patients with cholesterol gallstones who undergo lithotripsy, an adjuvant treatment with oral cholesterol solvent is mandatory. Extracorporeal biliary lithotripsy is free of mortality, and the morbidity is less than 5%. PMID- 2270373 TI - [A new strategy for graduate medical education. II]. PMID- 2270374 TI - [Quality control. VI. Patient data as quality indicator at an emergency laboratory]. PMID- 2270375 TI - [What is your diagnosis? Late diagnosed fractures of the spinous processes C7 to D1]. PMID- 2270376 TI - [Rational approach to peripheral arterial occlusive diseases]. AB - A growing proportion of over 65-year-old persons in the population will increasingly confront physicians with peripheral arterial occlusive disease. Intermittent claudication is the characteristic symptom of stage II disease at which most patients consult their physician. Known risk factors like cigarette smoking, diabetes, hypertension and hyperlipidemia have to be assessed. Manifestations of atherosclerosis in other vascular beds such as carotids and coronaries should be sought. Clinical angiologic evaluation with inspection, palpation of pulses, auscultation of vessels at rest and after exercise as well as measurement of the walking distance permits assessment of peripheral perfusion quite well. Oscillography and Doppler-sonography are increasingly used. Duplex scanning can replace angiography in many cases. Conventional and digital subtraction-angiography have their specific uses. Diagnostic and therapeutic measures recommended for peripheral arterial occlusive disease are summarized. PMID- 2270377 TI - [Conservative therapy of peripheral arterial occlusive disease]. AB - Strict control of risk factors and walking exercise are the basics to any medical treatment of arterial obstructive disease of the extremities. The benefit of platelet-aggregation inhibitors is well established. Acetylsalicylic acid slows the progression of recurrence of thrombotic occlusion after endarterectomy or percutaneous transluminal angioplasty in the femoral blood stream. Long-term oral anticoagulants are indicated after bypass surgery. Prostaglandin E1 and high energy phosphates are of proven benefit in patients with pain at rest. Vasoactive drugs such as Dipyridamole are still controversial. PMID- 2270378 TI - [Vascular surgery reconstruction in chronic arterial occlusive disease of the lower extremities]. AB - For the assessment of the indication for surgical intervention in chronic arterial occlusive disease, the patients complaints (clinical necessity), local operability and operative risk for the patient have to be considered. In stage II disease (intermittent claudication) the patients demand for symptom-free walking distance is decisive. A young, sporting patient will not accept a distance of 500 m whereas an old patient limited by cardiopulmonary insufficiency will accept less than 50 m. Stages III and IV mean marginal perfusion and endanger the extremity acutely. Persistent severe pain or trophic lesions force to surgical intervention. If vascular reconstruction is impossible amputation will become necessary although lumbar sympathectomy might be attempted before amputation. Because of better collaterals proximal arterial occlusions endanger the extremity less than more peripheral ones, even in the case of operative failure. At the pelvic level endarterectomy or prosthetic replacement are the choice procedures. Allografts are equivalent to autografts. Bypass is best used for the cruro femoral region. The material of choice is the autologous great saphenous vein. Below the knee it can be used as "in situ" bypass. Artificial prostheses give less favorable results. Inhibitors of platelet aggregation are used for protection of the arterial wall, anticoagulants for prevention of venous thrombosis and arterial re-embolization. PMID- 2270379 TI - [Fatigue fracture of the calcaneus]. AB - Formerly, stress-fractures of the metatarsus were the most common stress fractures. But over the last years, tibial and calcaneal localizations have dominated. The diagnosis of a calcaneal stress fracture is usually easy, provided the possibility is remembered. The symptoms are indeed vague, and radiological alterations are often not seen during the first 2 months. Sclerosis (callus formation) is the first finding on roentgenograms. A periosteal reaction like on tabular bone is never seen. Signs of a stress fracture are first seen on bone scan, but other nonstress-related bone abnormalities which have not manifested any radiographic changes such as early osteomyelitis, fibrous dysplasia, bone tumor, etc. have to be excluded. The treatment is simple. Vigorous activities are stopped for 6 weeks, soft heel pads are given, partial weight-bearing can be helpful for some days. Plaster is usually neither necessary nor useful. PMID- 2270380 TI - [Diarrhea and recurrent vomiting of fecal matter in a 56-year-old patient]. AB - A gastro-jejuno-colic fistula detected by upper gastric contrast-radiography was the cause of severe diarrhea, miserere and weight loss. It had developed after gastro-jejunal anastomosis. Surgical correlation was achieved by a single intervention, possible because of preoperative care and modern suture technology. PMID- 2270381 TI - [A case from practice (202). Ventricular septal defect (VSD) and aortic insufficiency]. PMID- 2270382 TI - [A case from practice (203). Bilateral renal medullary carcinoma with persistent microhematuria, right-sided nephroptosis without obstruction. Status following hysterectomy for uterine myomatosis]. PMID- 2270383 TI - [What is your diagnosis? Angiomyolipoma]. PMID- 2270384 TI - [Small intestine transplantation--a causal therapy in short bowel syndrome]. AB - The problems of surgical technique, graft physiology and immunological reactions in small-bowel transplantation have been investigated in extended animal experiments. In these experiments, the fundamentals of a successful clinical application of small-bowel transplantation could be laid. A successful human small-bowel transplantation could be carried out by the Kiel Group for the first time in 1988. A graft which had been removed from a related donor showed a complete adaptation after 22 months, so that the patient became completely independent from parenteral nutrition. After that, in several cases small-bowel and combined liver and small-bowel transplantation have been carried out. Thus, the clinical small-bowel transplantation represents the causal therapy of short bowel syndrome and should be developed in further clinical trials. PMID- 2270385 TI - [The significance of preoperative autologous blood donation in general surgery]. AB - In the surgical department of a county hospital, the total number of heterologous blood transfusions has been reduced by transfusing autologous blood units in elective surgery. Orthopedic, urologic, vascular and plastic surgery qualify mainly for autologous blood transfusion. PMID- 2270386 TI - [Mediastinal lymphadenectomy in bronchus carcinoma--techniques and problems]. AB - Mediastinal lymph node dissection in bronchial carcinoma patients means an additional procedure to the tumor resection. The en-bloc dissection is only possible if an upper lobe resection or a pneumonectomy is performed; otherwise, an isolated lymph node mapping is necessary. According to the different anatomical structures, mediastinal lymph node dissection is more easily performed on the right than on the left side, where mobilisation of the aortic arch or a longitudinal sternotomy is mandatory to sample the pre- and paratracheal lymph nodes. Up to now it is uncertain whether lymph node dissection improves the prognosis. But undoubtedly it is the basis for an exact staging. PMID- 2270387 TI - [Possibilities and limitations of heterotopic auxiliary liver transplantation]. AB - Although auxiliary heterotopic liver transplantation offers theoretical advantages over orthotopic liver replacement, clinical results have heretofore been dismal. After development of a technique of reduced size liver grafts provided with portal and arterial blood and venous drainage via the suprahepatic V. cava (HLT) in experimental animals, this method was applied in 21 transplantations in 19 patients. 11 of 16 patients with chronic liver insufficiency and one of three patients with fulminant liver failure survived transplantation for at least 1 year. HLT was well tolerated even by high-risk patients. Possibilities and limitations of this novel approach are discussed. PMID- 2270388 TI - [Enterostomy: preparation, construction and after care over time]. AB - During the last decade the industry has developed material to improve the quality of life of patients with an enterostomy. Patients are better informed and prepared before operation. Postoperative advising by professional nurses help the patient to maintain an odorless, leak-proof and continent stoma. Most of the patients today with enterostomies are able to have a socially integrated life with minimal psychological and physical handicaps. PMID- 2270389 TI - [Amputation or circulatory reconstruction in critical chronic ischemia of the lower extremities]. AB - As a rule, leg amputations in the elderly lead to an inability to walk and as a consequence to nursing-home care. The loss of body integrity and of psycho-social roots are responsible for the high mortality of 60% or more during in the first year after amputation. In case of imminent amputation, the crural arteries are almost always involved in the process of vascular occlusion. Only during the last 10 years has vascular surgery in the crural area become possible. Today crural reconstructions have a primary success-rate of over 90%, and in 60% of patients the leg can be saved in the long run. Even better long-term results may be expected through interdisciplinary collaboration and by the integration of microsurgical techniques. PMID- 2270390 TI - [Programming and rational use of a semi-adaptable articulator in complete dentures]. AB - In this article a simple and rational technique is described to make a complete denture. This technique is based upon the utilization of the articulator as an instrument necessary to the realization of the final prosthesis and as an intermediary between the general practitioner and the laboratory technician. As the physiology rules the determinants of the occlusion, the mandibular kinetics determines the orientation of posterior teeth. This way, step by step, the physiological recording of the condylar pathway, of the anterior guidance and of the level of the plane of occlusion will enable the laboratory to realize a set up of the prosthetic teeth to conform with the esthetic criterias. PMID- 2270391 TI - [Dental phobia]. AB - The observation of a sample of 2000 patients enabled us to individualize a group whose fright of dental care showed all the characteristics of a phobia in the ethological meaning of the term. Such a phobia definitely seems to have a link with an experience of pain during a previous dental treatment. It could be considered as a particular example of prepared learning. PMID- 2270392 TI - [An atypical case of tetanus with oral entry]. AB - This article reports a case of atypical tetanus localised exclusively in the head, with an oral point of entry very rare nowadays. With reference to this case, we describe the pathophysiology, clinical forms and the treatment of this infection. It is therefore essential that every practitioner, in the presence of a trismus, should consider the possibility of tetanus. PMID- 2270393 TI - [Paresthesia of the inferior alveolar nerve: clinical, diagnostic etiologic and prognostic signs, 2]. AB - This article is about the different iatrogenic (or others) mechanical and/or chemical trauma that can affect the mandibular nerve and which can lead to paresthesia. Depending on the different causes of the paresthesia, the prognosis for the nerve sensitivity regeneration will vary: in some cases treatment is necessary to make the symptoms disappear, in others expectation will be the rule and the prognosis is very poor. PMID- 2270394 TI - [Etiopathology and treatment of gingival hyperplasia in patients taking cyclosporin A]. AB - Since the use of cyclosporine A therapy in kidney, cardiac hepatitis livers pancrease transplants, the oral surgeon have seen gingival overgrowth under this immunosuppressive drug. In this article the authors reports 2 cases and accomplishes light and electron microscopic study. Gingivectomy is exposed. PMID- 2270395 TI - [Mandibular third molar. Conventional and surgical endodontic treatment: a challenge. Apropos of a case]. AB - A thorough clinical examination will help determine a precise diagnosis and a treatment plan in accordance with our patients expectations. A good prognosis will depend upon the strict observation of the rules regulating conventional endodontic and surgical treatments. PMID- 2270396 TI - Detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens in the serum and urine of patients with pneumonia in Papua New Guinea: comparison of latex agglutination and counterimmunoelectrophoresis. AB - Latex agglutination (LA) was compared with counterimmunoelectrophoresis (CIE) for the diagnosis of pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae type b in children less than 6 years old in Papua New Guinea. Neither LA nor CIE was sufficiently sensitive for the detection of pneumococcal antigens. CIE was superior to LA but had a sensitivity of only 60% (six of 10) in concentrated urine and a specificity of 90% (54 of 60). LA for the detection of H. influenzae type b had a sensitivity of 100% (eight of eight) relative to that of blood culture and a specificity of 99% (112 of 113) when urine diluted fivefold was tested, as compared with a sensitivity of 100% (nine of nine) and a specificity of 92% (56 of 61) in undiluted urine. Undiluted and concentrated urine specimens were unsuitable for LA because of the many false-positive reactions that resulted from nasal carriage of H. influenzae type b and nasal carriage of the cross-reactive S. pneumoniae type 6. CIE for the detection of H. influenzae type b had a sensitivity of only 44% (four of nine) in concentrated urine. PMID- 2270397 TI - Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in Highland children of Papua New Guinea. AB - Acute lower respiratory tract infection (ALRI) is the major cause of death among children in Papua New Guinea. This longitudinal study reports the bacteriologic findings for children observed in their hamlets. A total of 1,449 nasal swab specimens from 158 children less than 5 years of age who were studied intensively for 18 months were examined. Non-serotypable strains of Haemophilus influenzae were isolated from 91% of specimens, and serotypable strains were isolated from 35% (8% H. influenzae type b) of specimens. All children had acquired Streptococcus pneumoniae by the age of 3 months. The most frequently occurring serotypes of S. pneumoniae were 6, 19, and 23. Children more frequently carried invasive pneumococci during an episode of ALRI than when they were healthy. Also, children more frequently carried serotypable strains of H. influenzae during the 2 weeks preceding an episode of ALRI than when they were healthy. Between children analyses showed that children who were susceptible to attacks of ALRI and those who were not susceptible had similar rates of carriage of bacteria. PMID- 2270398 TI - Diversity of outer membrane protein profiles of nontypable Haemophilus influenzae from children from Papua New Guinea and the Philippines. AB - We determined capsular serotypes and, with use of SDS-PAGE, patterns of outer membrane proteins (OMP) of Haemophilus influenzae isolates from specimens of blood, lung, or CSF from children with acute respiratory tract infections or meningitis who were hospitalized in Papua New Guinea or the Philippines. Among 72 isolates from Papua New Guinea, 72% were type b, 14% were other encapsulated serotypes, and 14% were nontypable. The respective frequencies among 43 isolates from the Philippines were 56%, 7%, and 37%. The type b isolates could be subdivided into at least eight outer membrane subtypes, most of which have been described previously. In contrast, OMP profiles of the nontypable H. influenzae isolates from children in both countries were highly heterogeneous. These results differ markedly from those previously found for isolates from children with acute respiratory tract infections in Pakistan, for which encapsulated H. influenzae strains other than serotype b were not observed; 95% of type b isolates were of a single OMP subtype; and nontypable isolates showed evidence of clonal restriction. Candidate vaccines for use in developing countries as protection against disease caused by H. influenzae will need to include both capsular and noncapsular antigens and investigators must take into consideration regional differences among strains. PMID- 2270399 TI - Epidemiologic risk factors for children with acute lower respiratory tract infection in Buenos Aires, Argentina: a matched case-control study. AB - The risk factors that predisposed 516 hospitalized and 154 ambulatory patients to acute lower respiratory tract infection (ALRI) are examined in a matched case control study. The control group was selected from children attending immunization and well-baby clinics at the same institution that was treating the children with ALRI. Sex, age, nutritional status, socioeconomic level, as well as season and place of residence were used as matching criteria. Because of their distinct profiles, hospitalized and outpatient groups were analyzed separately. However, the four variables with the highest odds ratios (incidence ratios or relative risk) were found to be the same for both groups. These variables were related to the host's condition (bronchial hyperreactivity, presence of persistent symptoms of the upper respiratory tract), family (presence of acute respiratory tract disease in household members), and environment (indoor contaminants). PMID- 2270400 TI - Epidemiology of acute respiratory tract infections among Guatemalan ambulatory preschool children. AB - Acute respiratory tract infections (ARI) were studied during a 2-year period in 521 preschool children living in a marginal area of Guatemala City. There were 3,646 episodes of ARI detected during 26,329 child-weeks at risk, for an incidence of 14 per 100 child-weeks or 7.2 episodes per child per year. The median duration of ARI episodes was 11 days. The highest incidence of ARI was observed in children 6-23 months old. Boys had more respiratory tract illnesses than did girls; the presence of a cigarette smoker in the household was associated with higher morbidity. Acute lower respiratory tract illnesses (ALRI) were more common among younger infants 0-5 months old, with nutritional status having no apparent effect. Parental formal education and crowding in households were found to be directly related to the incidence of ALRI. In general, ARI morbidity interfered with appropriate physical growth. PMID- 2270401 TI - Epidemiology of acute respiratory tract infections among young children in Kenya. AB - The epidemiology of acute respiratory tract infection (ARI) was investigated in a rural community 80 km north of Nairobi, Kenya. This research was conducted prospectively on 250 families with 470 children less than 5 years of age who were contacted every 8 days during the 3-year study. The yearly incidence of respiratory tract infections decreased from 5.2 to 3.4 during the study; less than 5% of these infections involved the lower respiratory tract. The incidence was inversely related to age, and the illnesses were generally mild and brief in length. Fifteen children died during the study period. The precise causes of death are unknown, but respiratory infections possibly played a role in most cases. This study emphasizes the importance of determining the risk factors responsible for unusually severe morbidity and high mortality in children with ARI in developing countries. PMID- 2270402 TI - Child care practices with respect to acute respiratory tract infection in a poor, urban community in Nigeria. AB - A longitudinal study conducted over a 3-year period in a poor, urban community in Nigeria, a developing country, found that acute respiratory tract infection (ARI) was common, in particular among infants and boys. Between 81% and 95% of the children treated for ARI over the 3-year period were brought to the clinic by their mothers. About 32% of these children had been treated with cough medicines, 42% with antipyretics, 5% with antibiotics, and 10% with hematinics before they were brought to the clinic. The source of such medications included medicines left over from previous prescriptions and those bought from chemists' shops and street vendors. Up to 64% of the children treated for ARI had been force-fed local herbal teas by their mothers; herbal teas were used for both preventive and curative purposes. PMID- 2270403 TI - Acute respiratory tract infection in children in Idikan Community, Ibadan, Nigeria: severity, risk factors, and frequency of occurrence. AB - A longitudinal, community-based study of the epidemiology of acute respiratory tract infection (ARI) in children less than 5 years old was carried out in a community of low socioeconomic level in Ibadan, Nigeria. The annual incidence of ARI ranged from 6.1 to 8.1 episodes per child per year. The incidence was highest in the first 2 years of life and decreased with increasing age. The incidence was higher in boys than in girls. ARI occurred in all seasons of the year. The most common symptoms were cough, nasal discharge, and fever, while the most common signs referable to the respiratory tract were abnormal breathing sounds, tachypnea, and chest retraction. PMID- 2270404 TI - Malnutrition and acute respiratory tract infections in Filipino children. AB - The impact of malnutrition on morbidity and mortality associated with acute respiratory tract infection (ARI) was studied in Filipino children less than 5 years old. Malnutrition measured by weight-for-age Z-scores of less than -3 SD and less than -2 SD from the National Center for Health Statistics median reference population was associated with the following significant relative risks of morbidity: 1.24 (95% confidence interval [CI] = 1.14, 1.34) and 1.14 (95% CI = 1.08, 1.19), respectively, for ARI; and 1.9 (95% CI = 1.46, 2.39) and 1.2 (95% CI = 1.03, 1.47), respectively, for acute lower respiratory tract infection (ALRI). These risk ratios remained significant when adjusted for age, crowding, and parental smoking. Malnourished children with severe ALRI also had a mortality risk two to three times higher than that of healthy children. This risk remained significant even when adjusted for significant predictors of mortality, including clinical complications, concurrent measles, severe infections, and female gender; and for clinical factors, including extent of pneumonic infiltrates, dehydration, and hepatic enlargement. These findings underscore the importance of nutritional intervention in the control of morbidity and mortality among patients with ARI. PMID- 2270405 TI - Clinicopathologic studies of children who die of acute lower respiratory tract infections: mechanisms of death. AB - Clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined. The mechanism of death for these patients was multifactorial. Severe pneumonia alone accounted for 11 deaths (15.5%). Pneumonia associated with sepsis occurred in 42 children (59.2%). Heart failure (8.5%), hypovolemia (4.2%), and nosocomial infection (12.6%) were also seen in children with fatal acute lower respiratory tract infection. Extensive consolidation, squamous metaplasia, and hyaline membranes were present in the lungs of these children. Patients with severe disease must receive, in addition to antibiotics for acute episodes, individualized intensive respiratory and supportive care. Since these types of care are not available in poor communities, vaccination against measles and vitamin A supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease. PMID- 2270406 TI - Etiologic, clinical, and pathologic analysis of 31 fatal cases of acute respiratory tract infection in Argentinian children under 5 years of age. AB - During a 3-year survey of 805 children with acute lower respiratory tract infection (ALRI) who were admitted to three hospitals in Buenos Aires, 31 fatal cases were recorded--a fatality rate of 3.8%. Of the 31 children who died, 77% were less than 1 year of age, 48% were boys, 58% were malnourished, 29% had previous respiratory disease, and 22% had previous congenital disease. All children who died had clinical diagnoses of pneumonia (71%) or bronchiolitis (29%). Autopsies were performed in 14 of the cases. Viral etiology was determined by both cell culture and indirect immunofluorescence (IIF) assay of either nasopharyngeal aspirates (NPA) or lung tissue and bacterial etiology was determined by isolation of organisms from blood, lung tissue, and/or pleural fluid. NPA was examined for Bordetella pertussis by IIF. Pathogens were identified in 65% of fatal cases. Seven cases were bacterial; seven cases were viral; and six cases resulted from mixed infections. Lung tissue yielded positive etiologic results in 10 of 13 cases. Histopathologic examination performed on specimens from the 14 autopsied children revealed necrotizing bronchiolitis with intranuclear inclusions (n = 5) and multifocal pneumonia (n = 9). PMID- 2270407 TI - Respiratory rate greater than 50 per minute as a clinical indicator of pneumonia in Filipino children with cough. AB - The diagnosis and epidemiology of acute respiratory tract infection (ARI) in 199 children less than 5 years old were investigated in Manila. As part of this study, children who were treated at one of two outpatient clinics for cough of less than 3 weeks' duration were studied to test the validity of the use of a respiratory rate (RR) of greater than 50/minute for identifying ARI of a severity necessitating treatment with antibiotics. In the first population, in which 69% of the children had radiologically confirmed pneumonia, the sensitivity of a RR of greater than 50/minute was 54%, the specificity was 84%, the false-positive rate was 16%, and the false-negative rate was 46%. In the second population, in which 29% of the children had pneumonia, the sensitivity and positive predictive values were low. The validity of a RR of greater than 50/minute may vary in populations with different prevalences of ARI. PMID- 2270408 TI - Creation of a research program to determine the etiology and epidemiology of acute respiratory tract infection among children in developing countries. PMID- 2270409 TI - Overview of the symposium. PMID- 2270410 TI - The epidemiology of acute respiratory tract infection in young children: comparison of findings from several developing countries. Coordinated Data Group of BOSTID Researchers. AB - Investigators from 10 countries studied the epidemiology of acute respiratory tract infection (ARI) among children 0-59 months old. Data on incidence rates, by age, gender, and season; on pathogenic agents; on case-fatality rates; and on selected risk factor findings are presented. Incidence rates from six of the community-based studies ranged from 12.7 to 16.8 new episodes of ARI per 100 child-weeks at risk, and rates of lower respiratory tract infection (LRI) ranged from 0.2 to 3.4 new episodes per 100 child-weeks at risk. Children spend from 21.7% to 40.1% of observed weeks with ARI and from 1% to 14.4% of observed weeks with LRI. The incidence rates for ARI are highest in younger children. Viruses, especially respiratory syncytial virus, are isolated more frequently than bacteria from children with episodes of LRI. Risk factors exhibited different patterns of association with ARI in different studies. Interventions could have great impact on high-risk levels common in the study populations. These studies provide interesting and useful data on the epidemiologic dynamics of ARI. PMID- 2270411 TI - Etiologic and clinical evaluation of acute lower respiratory tract infections in young Argentinian children: an overview. AB - This paper summarizes the first study on clinical, etiologic, and epidemiologic features of acute lower respiratory tract infection (ALRI) in children in Argentina. A total of 1,003 children less than 5 years of age (805 inpatients and 198 outpatients) presenting with ALRI were studied during a 40-month period. Nasopharyngeal aspirate (NPA), blood, urine, and throat-swab samples were collected when each child was first seen for care. Virologic studies were performed on the NPA by means of indirect immunofluorescence and isolation of virus in cell culture. Bacteriologic studies primarily were done by means of culture of blood or pleural fluid (when available); Bordetella pertussis and Mycoplasma pneumoniae, however, were searched for by the use of immunofluorescence and complement-fixation testing, respectively, in paired sera. Respiratory syncytial virus was the most commonly isolated virus, followed by adenovirus, parainfluenza virus, and influenza virus. Streptococcus pneumoniae was the most frequently isolated bacterium, followed by B. pertussis and Haemophilus influenzae type b. Overall, the patient fatality rate was 3.8% among inpatients with pneumonia or bronchiolitis. PMID- 2270412 TI - Acute lower respiratory tract infections in hospitalized patients with diarrhea in Dhaka, Bangladesh. AB - This study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection (ALRI) and diarrhea in Dhaka, Bangladesh, and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens. The most common manifestations of ALRI were pneumonia (374 cases), bronchiolitis (12 cases), and tracheobronchitis (11 cases). The majority (77%) of the illnesses were in children less than 2 years of age, and 88% of the children were malnourished. A respiratory tract pathogen was identified in 30% of the patients, and a diarrheal pathogen was identified in 34%. The overall case-fatality rate in children with ALRI and diarrhea was 8%. The case-fatality rate was 14% in children with bacterial pneumonia and diarrhea, 3% in those with viral pneumonia and diarrhea, and 14% in malnourished children with shigellosis and ALRI. The most common respiratory tract pathogens were respiratory syncytial virus, Streptococcus pneumoniae, influenza viruses, and Haemophilus influenzae type b. PMID- 2270413 TI - Diagnoses of acute lower respiratory tract infections in children in Rawalpindi and Islamabad, Pakistan. AB - A hospital-based inpatient and outpatient study of 1,492 cases of acute lower respiratory tract infection (ALRI) was conducted from November 1986 to March 1988 in two hospitals in Rawalpindi and Islamabad, Pakistan. Specimens of nasopharyngeal aspirate were processed for viral studies in all cases; blood cultures were performed in 1,331 cases; and urine was obtained for detection of bacterial antigen in 378 cases, but 227 of these samples had bacterial contamination and were discarded. Respiratory syncytial virus was identified in 33% of cases, and Haemophilus influenzae and Streptococcus pneumoniae were identified in 9.6% and 9.9% of cases, respectively. Nonencapsulated H. influenzae accounted for 32% of the Haemophilus isolates, and type b was the only encapsulated H. influenzae strain identified. Of the S. pneumoniae serotypes isolated, 31% are not included in the currently available polyvalent pneumococcal vaccine. No clinical characteristic was demonstrated to be a reliable indicator for bacterial ALRI. PMID- 2270414 TI - Microbial agents associated with pneumonia in children from Uruguay. AB - The etiology of severe pneumonia, not frequently encountered in a community-based study, was determined in 204 hospitalized children less than 5 years of age. Potential pathogens were identified in 41% of episodes. Viruses were isolated or antigen was detected in 36.3% of cases; 82.4% of these cases were due to respiratory syncytial virus. Bacteria or bacterial antigens were identified in 13.2% of cases; Streptococcus pneumoniae and Haemophilus influenzae were the most frequently identified bacterial pathogens isolated from blood and/or pleural effusions. Mixed infections were identified in 4.9% of the episodes. Among the 17 patients with pleural effusion whose pleural space was drained, the etiology was suggested for 10 (58.8%). A clear-cut seasonal variation was seen, with the highest prevalence between May and October. Viral infections were more common in the first 6 months of life, although viral and bacterial infections were distributed throughout the first 5 years of life. PMID- 2270415 TI - Etiology of acute lower respiratory tract infection in children from Alabang, Metro Manila. AB - The etiology of acute lower respiratory tract infection (ALRI) was identified in 235 (43.8%) of 537 hospitalized children less than 5 years of age. Clinical evidence of measles was found in 258 (48.0%) patients, of whom 59 had a second viral infection. A viral agent was identified in an additional 121 patients, so that a total of 379 (70.6%) had viral infections. After measles, respiratory syncytial virus was the most common respiratory virus. Bacteremia was noted in 72 children (13.4%), occurring as frequently in children with measles (14.8%) as in those without (12.1%); Haemophilus influenzae and Salmonella typhi were predominant in the former, and H. influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were prominent in the latter. The presence of bacterial antigen in urine was not helpful in identifying bacterial infection. Extrapulmonary and intrapleural complications, concomitant measles, complicated ALRI, female gender, and malnutrition were associated with increased mortality among children with ALRI. The importance of measles immunization, vitamin A supplementation for alleviation of defects associated with malnutrition, and timely antimicrobial therapy is emphasized. PMID- 2270416 TI - Patterns of acute respiratory tract infection in children: a longitudinal study in a depressed community in Metro Manila. AB - The incidences of acute respiratory tract infection (ARI) and acute lower respiratory infection (ALRI) were 6.1 and 0.5 per child-year, respectively, in children less than 5 years old in a depressed urban community in Manila. The peak age-specific incidence occurred in those children 6-23 months old for ARI and 6 11 months old for ALRI. Age less than 2 years, malnutrition, household crowding, and parental smoking were associated with a statistically significant, though modest, increase in ARI morbidity. The crude mortality rate was 14.3 per 1,000 children 0-4 years old, with a corresponding ARI-specific mortality rate of 8.9 per 1,000. The prevalence of viral infection was 32.8 and that of bacteremic ALRI was 6.7 per 1,000 children with moderate ALRI. Respiratory syncytial virus was the predominant viral pathogen, while Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the most frequently isolated bacterial pathogens. Transmission of respiratory pathogens in depressed communities, facilitated by inadequate housing, inaccessible health services, and prevalent malnutrition, will continue unless meaningful socioeconomic improvement is realized. PMID- 2270417 TI - Acute respiratory tract infections among a birth cohort of children from Cali, Colombia, who were studied through 17 months of age. AB - For this study, 340 children less than 18 months old from a low-income, urban neighborhood in Cali, Colombia, were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection. All suspected cases were confirmed by trained doctors in a special clinic. Information on symptoms, signs, and potential risk factors was documented prospectively. Etiologic agents were identified in cases of lower respiratory tract infection (LRI). The overall incidence of acute respiratory tract infection was 6.6 cases per child-year at risk. The incidence of upper respiratory tract infection was 4.9 cases per child year at risk and that of LRI was 1.7 cases per child-year at risk. Crowding in the home was found to be significantly associated with an increased incidence of LRI. Respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with LRI. Staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with LRI. PMID- 2270418 TI - A community-based study of acute respiratory tract infection in Thai children. AB - A 2-year longitudinal study was conducted among the population of a socioeconomically depressed urban community in Bangkok, Thailand, from January 1986 through December 1987 to determine the incidence, etiologic agents, and risk factors associated with acute respiratory tract infection (ARI) in children less than 5 years of age. Data were obtained for a total of 674 children, who were visited twice weekly for detection of signs and symptoms of ARI. During the first year of the study, throat-swab specimens were obtained for bacterial culture from both ill and healthy children and a nasal wash was performed on mildly ill children for detection of virus. During both years of the study, nasopharyngeal aspiration for identification of virus was performed for children with more severe infection. The overall incidence of ARI was 11.2 episodes per child-year. The highest (14.9) and lowest (8.8) rates per child-year occurred in age groups 6 11 months and 48-59 months, respectively. Respiratory syncytial virus, parainfluenza virus, adenovirus, Streptococcus pneumoniae, and Haemophilus influenzae were the prevalent pathogenic agents identified. Factors associated with higher risk of ARI were low family income, working mothers, mothers with allergies, chronic malnutrition, and crowding in the home. PMID- 2270419 TI - A community-based study of acute respiratory tract infections in children in Uruguay. AB - Acute respiratory tract infection (ARI) was investigated in children less than 5 years old in a longitudinal community-based study of 166 families living in a socioeconomically depressed area in Montevideo, Uruguay. Pediatricians made home visits every 10 days from May 1985 to December 1987, and symptoms and signs of ARI were recorded. The incidence of ARI was 5.8 episodes per child-year during the first 12 months of life and decreased with increasing age of the index children; the rate was highest in children 1-5 months old. Children observed from birth were ill during 21% of the visits. According to the definitions of the study, the incidence of lower respiratory tract infection was 11.6% higher than the incidence of upper respiratory tract infections. The rates of ARI were higher during the colder months. Most risk factors for ARI were only marginally statistically significant. PMID- 2270420 TI - Identification of viruses in a study of acute respiratory tract infection in children from Uruguay. AB - For the purpose of identifying viral agents associated with acute respiratory tract infections (ARI) in children less than 5 years old, a longitudinal community study was undertaken in Montevideo, Uruguay, from May 1985 to December 1987. This report includes results obtained by cell culture and immunofluorescence techniques for detection of respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza 1 and 3 viruses, and adenovirus. Two populations were studied: children visited at home by pediatricians (group 1) and children with an ARI episode who attended an outpatient clinic (group 2). Nasopharyngeal aspirates were obtained at the time of an ARI episode: 858 from group 1 and 488 from group 2. Viruses were identified in 15.3% of group 1 specimens and in 17.6% of group 2 specimens. RSV was the most frequently recovered agent, accounting for 67.9% and 58.1%, respectively, of all viruses detected. The sensitivity and specificity of RSV isolation by cell culture are compared with detection by indirect immunofluorescence. PMID- 2270421 TI - Assessment of hypertension levels control and management (hypertension "AUDIT" project). Study in a population of workers. AB - The hypertension AUDIT project (WHO) was used for the study of large populations of workers in two Romanian industrial centers, Slatina and Sibiu, constituted into two main groups. The objects of the study were: the detection of new cases of arterial hypertension (AH) and of their proportion as compared with older cases, the assessment of the quality of diagnosis control and treatment methodology as well as the estimation of the patient's attitude regarding the conditions of treatment and of the physician's knowledge and attitude regarding AH. Group I (Slatina) included 22,839 workers and the program was applied in 15,740 randomly chosen subjects. Group II (Sibiu) included 14,874 workers of whom 2,838 were randomly chosen for study. From a total of 606 (6.20%) subjects aged 35 to 64 years with AH in both groups, 494 (81.51%) were older cases and 112 (18.48%) were newly detected. The prevalence of AH was found to increase with age and to be higher in women aged 55 to 64 years. The treatment in older cases from both groups was considered effective in 232 cases (46.96%) (of which 26 (11.2%) with overtreatment) and insufficient in 262 (53%). The reasons alleged by the patients for the late detection of AH were the absence of symptoms and a casual interest for their state of health. The risk factors were systematically checked. Smoking was found in 30.36% of the subjects in group I and in 31% of those in group II. The use of diagnostic laboratory procedures was corresponding to the present recommendations. The nonpharmaceutic therapy was frequently recommended, especially reduction of salt consumption. Besides that, pharmaceutic treatment was indicated in most of the patients (63% in group I and 90% in group II). Diuretics (41.26% in group I and 75% in group II), and beta blocking drugs (35.3% in group I and 70% in group II) were the most frequently administered and in a lesser proportion vasodilators with central or peripheral action, calcium blockers, Rauwolfia and angiotensin conversion enzyme inhibitors. The consumer inquiry showed satisfactory compliance of patients, most of them took their tablets regularly, were satisfied with the medical assistance and preferred to consult the same physician. The data of the physician inquiry regarding diagnosis treatment of AH and professional training also proved satisfactory. The use of the AUDIT project has allowed a complex estimation of AH in the groups studied and will prove useful for a more efficient control of AH in the whole population. PMID- 2270422 TI - Microalbuminuria, as predictor of late diabetic complications. A prospective study. AB - To assess the predictive value of microalbuminuria (M) for diabetic macro- and microangiopathy, neuropathy and some related risk factors studies were carried out in 105 diabetic subjects. All examinations were repeated after one year. Microalbuminuria was found to parallel all late diabetic complications, at the beginning of investigations and also after a one-year evolution. It also positively correlated with some risk factors for angiopathy, such as plasma lipid parameters, blood pressure, body mass index and duration of disease. PMID- 2270423 TI - Biochemical changes induced by Campylobacter pylori in the gastric juice. AB - The biochemical changes induced in the gastric juice by the presence of Campylobacter pylori (CP) were followed up in 151 patients with various gastric and duodenal diseases. The diagnosis of CP infection was made by the urease test. In the presence of CP urea decreased in the gastric juice and ammonia increased. The sialic acid, fucose and hexoses, glucide components of the mucus glycoproteins dissolved in the gastric juice, underwent no change in the presence of CP. The hexosamines in the gastric mucus increased significantly in CP patients. Urease activity is present in the gastric juice even in the absence of CP, probably due to other microorganisms present in the human stomach. This does not exclude the use of the urease test for the diagnosis of CP infection. However the test can only be used in the bioptically removed gastric mucosa samples, not in the gastric juice. PMID- 2270424 TI - Clinico-biologic aspects and evolutive tendencies in sacroiliitis. AB - A group of 103 patients with radiologic changes of sacroiliitis were investigated and followed up over a mean period of 3.5 years. The biologic explorations (nonspecific inflammatory tests, humoral immunologic determinations and serum fibronectin assay) as well as sacroiliac and spine radiographic examinations, were repeated every 6th-12th months. In 32 patients (31%) clinical, biologic and radiologic signs of evolutive disease, were detected. In such cases, sacroiliitis representing in fact a form of onset of ankylosing spondylitis, the HLA-B27 phenotype was also determined and was found present in 8 cases. Of the biologic tests the decrease of serum fibronectin proved the most significantly correlated with evolutive tendency of sacroiliitis. PMID- 2270425 TI - Possibilities of perfecting antimicrobial therapy. Dynamics of penicillin G concentrations in the cerebro-spinal fluid in purulent meningitis. AB - In 43 adult patients with purulent meningitis receiving daily doses of 1 4,000,000 IU penicillin G i.v. in bolus, determinations were made, 1-6 hrs after administration, in 153 samples of cerebrospinal fluid (CSF), to ascertain the concentrations of penicillin that have reached the CSF. After 1 hour maximum levels of penicillin were noted, exceeding by far the meningococcus and pneumococcus minimum inhibitory concentration (MIC). Generally, high penicillin concentrations persisted in the CSF, in most of the cases at least for the following 6 hours. The advantages of using penicillin G i.v. in doses of 1 3,000,000 IU in bolus at 12 hour intervals are discussed. All the 36 patients with meningococcal meningitis and 3 of the 5 with pneumococcal meningitis recovered with this therapeutic scheme, under daily control of the CSF. PMID- 2270426 TI - Double atrial and double ventricular parasystole. Case report. PMID- 2270427 TI - Aberrant intraventricular conduction and reciprocal beats. Two case reports. AB - Supraventricular rhythm disturbances with aberrant intraventricular conduction are sometimes interpreted as ventricular dysrhythmias, an error with important therapeutic implications. In the two cases reported below, the ignorance of signs suggestive for a ventricular aberrance has led to confusions of diagnosis and therapy. PMID- 2270428 TI - Pancreas transplantation. Experimental and clinical trials. AB - The ever increasing incidence of diabetes mellitus has stimulated the immunologic investigations concerned with the role of heredity and the toleration rate of transplants of pancreas organ or islet structures. Concomitant or subsequent trials have attempted to define or avoid the apparently diabetogenic factors. With respect to the effectiveness of diabetes therapy, one cannot deny the contrast between the practical and the theoretical aspects. Besides the technical difficulties, the pancreas organ or islet cell transplants are confronted with the still limited possibilities of immunosuppression. The recent concept of a bioartificial organ is an attempt to avoid such disadvantages. The present paper is a review of the main achievements of the experimental and the clinical trials in the above-mentioned directions of research work. PMID- 2270429 TI - The Nobel lectures in immunology. The Nobel Prize for Physiology or Medicine, 1919, awarded to Jules Bordet 'for his discoveries relating to immunity'. PMID- 2270430 TI - Jules Bordet--a giant in immunology. PMID- 2270431 TI - Phenotypic and functional changes of tumour cells from patients treated with monoclonal anti-idiotypic antibodies. AB - In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F., B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype. In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease--at relapse an impressive tumour regrowth rate with constant serum idiotype level--suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression. In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell. We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R., whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear. PMID- 2270432 TI - Suppression of target cell proliferation by natural killer cells. AB - The cytolytic effects of natural killer (NK) cells have been extensively studied in recent years. In the present study we have investigated the cytostatic effects of NK cells. Human peripheral blood lymphocytes from healthy volunteers were used as a source of effector cells, and the cell lines K562, U937, U1285, and Molt-4 were used as target cells. Effector cells were enriched for NK cells using Percoll gradients and depleted of NK cells on Percoll gradients or by using Leu 19 antibodies and magnetic beads. By monitoring cell numbers during co-culture of effector cells and K562, it was found that after an initial phase of cell killing for 3 h target cell numbers remained stable during the following 24-48 h. In a microcytotoxicity assay measuring inhibition of uptake of [3H]thymidine, the four target cell types were shown to have different NK sensitivity; inhibition of greater than or equal to 80% was obtained for K562 and U937 at an effector to target cell (E/T) ratio of 30:1, 50% for U1285, and 30% for Molt-4. This inhibition was shown to be partly a direct effect on DNA synthesis for all cell lines, as incorporation of [3H]thymidine was decreased in cocultured target cells compared with an equal number of target cells alone. Inhibition of DNA synthesis was thus not directly related to cell death and was also observed for the Molt-4 cell line that was not killed. A cell division assay, with target cells in agarose and effector cells in a liquid upper layer, showed a decline in the rate of target cell divisions. Effects on the cell cycle were studied on latent-phase cells. It was shown that effector cells delayed the onset of DNA synthesis. This anti-proliferative effect was observed for several days, but cell growth then gradually resumed. The effector cells were identified as CD56-positive large granular lymphocytes (LGL). Double-layer cultures and experiments using effector cell supernatants demonstrated that the growth-inhibitory effect could be mediated by soluble factors, and the production of such factors was stimulated by exposure to a small proportion of target cells (50:1). Studies with specific antibodies indicated that growth inhibition was not mediated by alpha interferon (IFN-alpha) but it was partly mediated by tumour necrosis factor alpha (TNF alpha). It is concluded that NK cells have a growth-inhibitory effect that is distinct from the cytolytic effect and this activity is probably mediated by several soluble factors including TNF-alpha. PMID- 2270433 TI - Expression of the alpha-chain gene in heterogeneous IgA immunodeficiency. AB - Five heterogeneous IgA-immunodeficient patients were analysed for expression of the alpha-chain gene. The number of surface IgA-bearing B cells was low in four patients. Southern blot analysis indicated no deletion of immunoglobulin structural genes coding for C alpha or alpha switching-region genes. The number of surface IgM and IgA double-bearing B cells increased in some patients. Addition of recombinant interleukin 4 (rIL-4), rIL-5, and rIL-6 to the normal B cells enhanced IgA production. However, B cells of the patients showed no or one third lower IgA production in response to these lymphokines, even though there was proliferation. rIL-4, rIL-5, and rIL-6 induced low or no expression of alpha mRNA of the patients' B cells. These results suggested that the patients lacked B cells able to produce transcripts for the IgA heavy chain, and that some patients' B cells might be defective at the switch-recombination process from mu to alpha or from mu and alpha to alpha. PMID- 2270434 TI - Alteration of membrane oligosaccharides by castanospermine, an alpha glucosidase inhibitor, enhances immunoglobulin production in Staphylococcus aureus Cowan I stimulated lymphocyte culture. AB - Castanospermine (CSP) inhibits alpha-glucosidase, which is involved in the initial step of N-linked oligosaccharide processing of secretory and membrane glycoproteins. In Staphylococcus aureus Cowan I (SAC)-stimulated human lymphocyte culture, CSP at a dose of 20 micrograms/ml caused a twofold increase in immunoglobulin G (IgG) release after 7 days. An initial 48-h exposure to CSP sufficed for this enhancing effect. Plaque-forming cell assays on the seventh day disclosed that CSP caused an increase in the number of IgG-, IgA- and IgM secreting cells. In cross-culture experiments, only a mixture of B cells pretreated with CSP and untreated T cells showed an increase in IgG production. Tritiated thymidine incorporation studies revealed that CSP enhanced B-cell responses to T cell-derived soluble factor (TSF). When incubated with CSP for 18 h, B cells showed an increased surface binding on [3H]concanavalin A (Con A). These results indicate that the alteration in B-cell membrane oligosaccharides enhances the response to TSF at an early stage of SAC culture, leading to an increase in Ig-secreting cell number at later stages. The present study provides evidence that cell-surface oligosaccharides of B cells play an important role in the responses of B cells to lymphokines. PMID- 2270435 TI - Synthesis of C3, C5, C6, C7, C8, and C9 by human fibroblasts. AB - We investigated the ability of human fibroblasts to produce the components of the final common pathway (C3-C9) of complement in vitro by co-culturing an alternative complement activator (agarose beads) with the cells. The test system involved incubation of beads with anti-complement antibodies followed by radioactive-labelled anti-Ig detection antibodies. Subsequently, the beads were examined in a radioimmunoassay. Our results indicate that human fibroblasts produce C3, C5, C6, C7, C8, and C9. A neoepitope selectively expressed on activated C9 was detected, indicating assembly of the terminal complement complex and thus formation of a functional terminal complement pathway by the fibroblasts. PMID- 2270436 TI - Alloreactive T cells. PMID- 2270437 TI - Site of catabolism of autologous and heterologous IgA in non-human primates. AB - Because of similarities between the human and monkey immune systems, we considered the monkey a suitable model for studies on the catabolism of various molecular forms of IgA, for which little information is available. The residualizing label dilactitol-[125I]tyramine was coupled to monkey (Macaca fuscata) IgA and IgG, as well as to human monomeric and polymeric myeloma IgA1 and IgA2 proteins. When labelled proteins were injected intravenously into monkeys, the non-metabolizable radioiodinated tracer accumulated at the cellular site of protein degradation, allowing identification of the catabolic sites. To determine the uptake of injected proteins by various tissues, monkeys were sacrificed 6-7 days after injection of labelled proteins, when blood-associated radioactivity was less than or equal to 10% of the injected dose, as measured by plasma clearance. When monkey or human monomeric IgA, as well as human polymeric IgA, irrespective of subclass, was administered to monkeys, the liver showed the greatest tissue uptake relative to total dose injected and to organ weight, and the highest acid soluble radioactivity (degraded protein). Although both hepatocytes and non-parenchymal liver cells were involved in IgA uptake, the hepatocytes were more active. Therefore, it appears that the liver is the major site of uptake and catabolism of IgA in monkeys and possibly in humans. PMID- 2270438 TI - Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures. AB - We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is concluded that the epithelial stromal cells of the thymus, by acting as veto cells, may be responsible for the negative intrathymic selection of self-reactive thymocytes leading to elimination of the vast majority of immature thymic lymphocytes. PMID- 2270439 TI - Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumour necrosis factor production. AB - We studied functions of polymorphonuclear leucocytes (PMN) and monocytes from peripheral blood of subjects with familial hypercholesterolaemia (FH). FH monocytes exposed to Escherichia coli lipopolysaccharide (LPS) in 10% human AB serum generated tumour necrosis factor (TNF) significantly more than did control monocytes. After lowering of serum low-density lipoprotein (LDL) levels by drug treatment, FH monocytes exposed to LPS in the absence of exogenous lipoproteins generated significantly more TNF than did control monocytes. These findings suggest that increased TNF production is not affected by hypolipidaemic treatment and may not derive from differences between uptake of exogenous LDL by FH monocytes and control cells. Chemotaxis, chemokinesis, and random migration of both FH PMN and FH monocytes were normal, as determined by agarose assay and membrane filter assay. FH PMN showed increased luminol-enhanced chemiluminescence in response to 2.5 x 10(-8) M, but not to 2.5 x 10(-6) M, N-formyl-methionyl leucyl-phenylalanine, and not to serum-treated zymosan or to phorbol myristate acetate. Luminol- and lucigenin-enhanced chemiluminescence responses of FH monocytes were normal. In summary, the major aberration found in the present study was that FH monocytes stimulated with LPS show enhanced production of TNF. The possibility that exaggerated TNF production contributes to an early development of atherosclerotic lesions in FH subjects warrants further studies. PMID- 2270440 TI - Distribution and characterization of autoantibodies to interleukin 1 alpha in normal human sera. AB - Antibodies against IL-1 alpha were detected in sera of apparently healthy individuals. The immunoglobulins belonged to the IgG class, particularly IgG1, IgG2, and IgG4. [125I]rIL-1 alpha bound to Fab fragments of IgG, and IgG immune complexes of molecular weights from 160 to 700 kDa were formed in the sera by [125I]rIL-1 alpha. The occurrence of detectable anti-IL-1 alpha IgG in sera of 32 male and 32 female donors was 25 and 22% respectively. As judged by Scatchard analysis of the binding data, the capacity and avidity of binding were greater in the male than in the female sera (mean capacity to bind [125I]rIL-1 alpha: 10 [0.7-27] versus 3.3 [0.5-7.3] ng/ml; and mean Kd: 5.5 [5-7] versus 11 [4-16] pM). The antibodies did not cross-bind human recombinant IL-1 beta, IL-2, IL-6, or tumour necrosis factor alpha (TNF-alpha). It is concluded that native IL-1 alpha seems to trigger production of specific, high-avidity IgG antibodies in a relatively large number of normal individuals. These autoantibodies may regulate immunoinflammatory processes involving IL-1 alpha. PMID- 2270441 TI - [Between nihilism and fanaticism: the ethics of prevention]. AB - Opinions diverge on the ethics of preventive medicine. A balance needs to be struck between nihilism (doing nothing) and fanaticism (doing too much). The authors consider the ethical aspects of preventive medicine from the practising physician's viewpoint. Various aspects can be identified: SCIENTIFIC AND METHODOLOGICAL: Like any medical act, preventive practice relies on good scientific data. The epidemiologic studies should be clinically relevant and their recommendations must be interpreted critically before being incorporated into clinical practice. It should not be forgotten that we are dealing with patients and their behaviour. Tactful dialogue and personalized intervention are essential. DEONTOLOGICAL: Modern medicine is oriented toward health maintenance and promotion, thus including prevention. Although the community has drawn obvious benefits from preventive practices such as the use of vaccines, prevention must not be allowed to become a medical tyranny. Respect for the individual should remain its central concern. ETHICAL: The "meaning of life" must not be forgotten. Factors such as quality of life should always be kept in mind in measuring the benefits of prevention. By providing objective information and tailored counselling, the aim of prevention is to encourage expression of the individual's own responsibility for her/his own health. FINANCIAL: Preventive medicine is not covered by health insurance schemes. Cost-benefit analysis should consider not only the economic aspects of prevention but also its positive impacts on the entire social field. SOCIAL AND CULTURAL: The findings of epidemiologic studies must be adapted to precise socio-cultural environments. In our culture, for example, caregivers should be the first to practise what they preach. It must also be remembered that at the present time the basic preventive measures are still not accessible to everyone. PMID- 2270442 TI - [Prevention and screening: which decisions should be made?]. AB - The definition of the various types of prevention, of screening and of case finding are recalled, and the particular requirements of screening within an apparently normal population are analyzed. The characteristics of a screening test are reviewed, with emphasis on the prevalence of the disease, which, together with the specificity of the test, conditions the positive predictive value. The consequences of the false positive and false negative are briefly detailed and the benefit/cost ratio is defined. Interpretation of the results is rendered difficult by the existence of certain biases including the lead-time bias and the length-time bias. These complex elements should be taken into consideration in a physician's regular case-finding in his patients. PMID- 2270443 TI - [Office emergencies--hospital emergencies]. AB - The treatment of emergencies in a hospital or in private practice is subject to a common set of rules, but each setting presents its own particularities. These specificities include the prevalence of different pathologies, the possibility of hospitalisation and the length of the observation period, and these are illustrated by pertinent case histories. The effect of different prevalence is well illustrated by the thrombolytic treatment of myocardial infarction. The cost/benefit ratio of this treatment is entirely different when administered to a population seen in private consultation, in which myocardial infarction makes up only 5% of patients presenting with thoracic pain, as opposed to a hospital setting in which the prevalence of myocardial infarction is much higher. The possibility of hospitalizing patients is illustrated by community-based pneumonia, in which knowledge of the epidemiology and prognostic factors are guides in choosing appropriate antibiotics and in rapidly selecting the patients requiring admission to hospital. Finally, the length of observation is illustrated by patients presenting with abdominal pain. Certain symptoms and signs can indicate a surgical affection, but often a certain period of observation is required before the correct diagnosis can be made. To improve physicians' performance in emergency medicine will require better knowledge of areas up till now often ignored, such as epidemiology, decision analysis, a probabilistic approach to different pathologies, unfavourable prognostic factors of known illnesses, and simple clinical and paraclinical factors which serve to discriminate between those cases requiring hospitalisation and those which may be followed on an ambulatory basis. PMID- 2270444 TI - [Continuing education course of the Swiss Society of Internal Medicine in the form of a workshop: the ideal formula?]. PMID- 2270445 TI - [Clinical practice and informatics: medical informatics understood by the clinician]. PMID- 2270446 TI - [Survival of HIV-positive patients hospitalized in intensive care for respiratory insufficiency and pneumocystis carinii pneumonia]. AB - Respiratory failure secondary to Pneumocystis carinii pneumonia (PCP) is associated with high mortality in AIDS patients. In a search for prognostic indicators, we reviewed hospital charts of 13 AIDS patients admitted to our intensive care service from 1982 to 1989. Mortality rate was higher from 1982 to 1987 (4/5 patients) than later (3/8 patients). There was no significant difference between survivors and non survivors of this acute episode with regard to sex. HIV risk factors, time elapsed since AIDS diagnosis, vital signs (blood pressure, heart rate, respiratory rate), hemoglobin, white blood cell count, platelets, total and T4 lymphocytes, electrolytes, lactate dehydrogenase, P24 antigen Apache II and SAPS scores and corticosteroid treatment. Higher mortality was associated with more advanced age and an oxygen alveolar-arterial gradient greater than 65 mm Hg with an inspired fraction of oxygen of 0.21. We conclude that only the alveolo-arterial gradient could represent a prognostic indicator of practical interest. It is our belief that improvement since 1988 can be explained by earlier diagnosis and prompt treatment before development of severe lung alterations. PMID- 2270447 TI - [Hyperkalemia with potassium-sparing and potassium-losing diuretics. Results from the Comprehensive Hospital Drug Monitoring Bern (CHDM)]. AB - Of 5047 in-patients in the Division of Internal Medicine, Zieglerspital Bern (regional/teaching hospital), admitted from 1982 to 1985, 2412 were treated with at least one diuretic. The hospital records of these patients were reviewed with regard in particular to serum potassium and creatinine values as well as potassium supplementation. On the basis of this evaluation the patients were assigned to 6 different treatment groups and the relative occurrence rate of hyperkalemia probably related to drug treatment was determined. Of the 590 patients treated with only potassium losing diuretics, none was found to show a hyperkalemia event; of the 742 patients on potassium losing diuretics and potassium supplementation, 27 (3.6%) developed hyperkalemia. In the 439 patients under combined diuretics (potassium sparing with potassium losing) without potassium substitution, 76 (17.3%), and in the 381 under combined diuretics with potassium substitution 24 (6.3%), developed hyperkalemia. The further groups of patients are also described. Renal function was estimated by the formula of Cockcroft and Gault. Reduced renal function is a significant risk-factor for hyperkalemic events under combined diuretics. All hyperkalemic events were within a serum potassium range of 5.1-7.0 mmol/l. PMID- 2270448 TI - [Hematological parameters and prognosis in established or imminent HELLP syndrome. Apropos of 12 case reports]. AB - We describe the clinical and biological characteristics of 12 pregnant women with the HELLP syndrome as defined by Weinstein in 1982 (H for hemolysis, EL for elevated liver enzymes and LP for low platelet count). The data demonstrate that this syndrome is an obstetric emergency threatening the lives of both mother and child. However, if delivery is prompt the prognosis is good. The suspicion of gestosis requires a hematological assessment (complete blood count and close examination of blood film, evaluation of hemostasis) as an essential component in therapeutic decisions. PMID- 2270449 TI - [Isolated prolongation of the PTT: 2-year retrospective study]. AB - The hemorrhagic risk associated with isolated prolongation of the PTT has been evaluated in a 2-year retrospective study. Of the 60 cases thus found, a hemorrhagic risk was present in 15 patients of whom 7 had hemophilia A, 5 von Willebrand's disease and 3 factor XI deficiency. Among the other etiologies not associated with a bleeding tendency, there were 31 proved or suspected cases with inhibitors of the PTT, most of whom were children, 2 factor XII deficiencies, 2 prekallikrein deficiencies and 4 contact phase activations. Isolated prolongation of the PTT is therefore without specificity and needs further investigation of hemostasis to determine the associated hemorrhagic risk. PMID- 2270450 TI - [Prekallikrein deficiency: apropos of 2 cases]. AB - An isolated, considerably prolonged aPTT (117 and 112 sec respectively; normal range 26-36 sec) was discovered during the preoperative workup in 2 patients aged 48 and 66 years. Both had a negative personal and family history for bleeding. Levels of the intrinsic coagulation factors which potentially cause a bleeding risk (VIII, IX, XI) were normal, and an inhibitor of the aPTT could not be detected. Investigation of the contact phase revealed a severe functional deficiency (less than 1%) of prekallikrein (PK) which was diagnostic of the homozygous state. Complete correction of the aPTT after prolonged activation of the contact phase and after addition of 0.2 volume of normal plasma to the sample is suggestive of this diagnosis, which needs to be confirmed by determination of the functional PK. Though deficiency of PK does not carry a bleeding risk, it is important to identify such cases in order to avoid time-consuming investigations in a surgical emergency situation. PMID- 2270451 TI - [The evaluation of prescribing practice in a general internal medicine outpatient clinic with special reference to gastrointestinal medicines]. AB - Prescribing patterns of 13 residents in a medical outpatient clinic were evaluated between March and June 1986. Prescribed drugs influencing the gastrointestinal tract were also analyzed in order to define quality of the therapeutic process. Advertising for these special drugs in 3 Swiss medical journals was analyzed and compared with the prescribing behavior of participating physicians. 6300 patients with 3346 prescriptions (0.5 prescription/patient) were enrolled in the study. 16.5% of all prescriptions involved cardiovascular, 13.5% gastrointestinal, 9.5% non steroidal antirheumatic, 9.1% analgesic, 7.7% psychotropic and 7.4% antibiotic drugs. The share of 14 other classes of drugs was less than 4%. 471 prescriptions of gastrointestinal acting drugs were distributed over 288 patients (0.6 prescription/patient). 160 patients had irritable bowel syndrome, 40 ulcer disease, 23 inflammatory/infectious bowel disease, 18 gastroesophageal reflux, 18 anal diseases, 11 other gastrointestinal disorders and 15 were treated without diagnosis. Distribution of drugs was as follows: 27.5% bulk laxatives, 26% antacids, 15.7% H2-receptor antagonists, 13.5% anticholinergic agents, 4.9% laxatives, 3.4% loperamide, 9% other drugs. There was an increase in prescriptions per visit from 0.8 in 1980 to 1.5 in 1986. No important influence of drug advertising in 3 different medical journals published between January and June 1986 could be found. Considering the documented diagnoses, the therapeutic decisions were correct in 95.5% of cases treated. In conclusion, drug prescribing habits are permissive, the therapeutic approach is acceptable and the influence of drug advertising is negligible. PMID- 2270452 TI - [Central analgesic effect of paracetamol]. AB - Although biochemical data suggest a direct effect of paracetamol on the CNS, its mode of action is still poorly understood. We investigated the central impact of paracetamol compared to acetylsalicylate in response to transcutaneous electrical nerve stimulation in man. Healthy volunteers received i.v. paracetamol, acetylsalicylic acid, and placebo. Analgesia was assessed by measurement of objective (R-III reflex) and subjective (VAS) pain thresholds. A close correlation was observed between both objective and subjective thresholds. Paracetamol raised the objective and subjective thresholds. In contrast, acetylsalicylic acid had no noticeable effect on either threshold. These data demonstrate a central analgesic effect of paracetamol. PMID- 2270453 TI - [Lowering of the incidence of puerperal mastitis in the sow by protection of the mammae from contamination]. AB - Twelve sows each farrowed in an experimental pen designed especially for this study or in a crate. Viable counts of enterobacteriaceae were performed in samples taken from the laying area and from the teats. Secretion from every mammary complex was examined repeatedly for bacteria and for somatic cells. The sows in the experimental pen did not lay down in their own faeces. The viable counts in samples from the laying area and the teats were much lower than with the sows kept in farrowing crates. Infection with E. coli was observed in 3 mammary complexes of the sows in the experimental pen as compared to 27 complexes of the sows in the crate. More than half of the infections was detected in the samples taken before farrowing began. In the average the bacteria persisted for 1.3 days. On the first 4 days of life piglets sucking teats with cytologically defined mastitis had an average daily gain of 105 g as compared to 125 g with piglets sucking healthy teats. In conclusion puerperal mastitis is a consequence of faecal contamination of the mammary gland. Soiling of the laying area with faeces and urine can be reduced by improvements in the farrowing accommodations. PMID- 2270454 TI - [The vascularization of the epididymis of the boar with special reference to perfusion fixation]. AB - Vasculature of the epididymis was investigated by means of corrosion casts. In the boar, epididymal arteries form a complex network around their stem vessel, the testicular artery. Proper perfusion fixation or complete casting therefore require direct injection into one of these branches. To reach the distal cauda, cannulation of the deferential artery is further needed. Connections between all of these feeding vessels occur at the level of the vascular cone. A prominent anastomosis between an epididymal branch and the testicular artery is regularly observed under the caput epididymis. Epididymal veins drain to a large extent into the pampiniform plexus. Unlike the situation in other species, vascularization of testis and epididymis are closely associated in the boar. PMID- 2270455 TI - [Spinocellular epithelioma of the skin: etiology of the eczema syndrome in budgerigars (Melopsittacus undulatus) and lovebirds (Agapornis sp.)]. AB - Squamous cell carcinoma in the axilla, unilaterally as well as bilaterally, is described pathologically in three love-birds and two budgerigars. The deep, hemorrhagic ulceration with secondary bacterial and/or mycotic infection corresponds to the "EMA-Syndrome". PMID- 2270456 TI - [Causes of death and disease in kittens]. AB - Post-mortem examinations were carried out on 168 kittens 0 to 12 weeks of age. One third of the kittens died of an infectious agent, one third showed non infectious illnesses and in one third the examinations revealed none or vague results. PMID- 2270457 TI - Field effects. A health worry for electric blanket makers. PMID- 2270458 TI - Double trouble. When identical twins are not identical. PMID- 2270459 TI - Acacia trees kill antelope in the Transvaal. PMID- 2270460 TI - How cells maintain stability. PMID- 2270461 TI - The legacy of Gestalt psychology. PMID- 2270462 TI - Frozen and alive. AB - A variety of animals freeze solid during the winter months and thaw in the spring. This natural ability to survive freezing may yield clues to the cryopreservation of human tissue. PMID- 2270463 TI - The emergence of modern humans. AB - The theory that all humans are descended from a recent African ancestor was promoted by geneticists who study living populations. The fossil record provides independent support for this model. PMID- 2270464 TI - Does mercury from amalgam restorations constitute a health hazard? AB - Amalgam is the most extensively used implant material in dentistry. There have been no clinical trials of this substance and there are no epidemiological studies that allow any conclusions on the safety of amalgam fillings. Amalgam restorations continuously emit mercury vapour, which is absorbed in considerable quantities via the lungs. A comparison with dose-effect relationships, obtained in occupational studies, for certain effects on the kidneys and central nervous system (CNS), suggests that individuals with unusually high emission of mercury from amalgam fillings are at risk. It is unclear whether or not clinically significant effects could be expected. The limited sensitivity of available occupational studies, together with insufficient knowledge of possible host factors affecting resistance to mercury, implies that other more severe effects in susceptible individuals cannot be excluded. Information on long-term effects on organs other than brain or kidney is sparse. Animal studies suggest the possibility of immune system reactions to mercury, i.e. development of autoimmunity, that are not primarily dose-dependent, but rather depend on genetic susceptibility. From a toxicological point of view, amalgam is an unsuitable material for dental restorations. PMID- 2270465 TI - Lack of significantly positive correlations between elemental concentrations in hair and in organs. AB - Elemental concentrations (Ca, Cu, Fe, Mg, P, Se and Zn) in the hair of Japanese were examined in relation to those in internal organs (cerebrum, cerebellum, heart, spleen, liver, kidney and rib). No significantly positive correlation was found between elemental concentration in hair and that in internal organ. This result indicates the restricted use of hair as a medium for the estimation of nutritional status of the essential elements examined in the present study, at least on an individual basis. The correlations between the concentrations in organs are also presented. PMID- 2270466 TI - Study of environmental pollutants in and around the city of Lahore. I. Determination of lead in blood of various population groups. AB - Lead concentrations in 102 blood samples collected from seven different population groups living in and around the city of Lahore were determined. Gender differences in blood lead were statistically insignificant for normal males and normal females and also for male and female cancer patients. The differences between exposed male industrial workers and exposed females were statistically significant (P = 0.05). No correlation was observed between age and blood lead for normal males and cancer patients of both sexes. Blood lead levels in the male groups were generally higher than in the corresponding female groups. Much higher blood lead concentrations for cancer patients of both sexes, i.e. 69.63 microgram dl-1 for males and 52.41 microgram dl-1 for females, were observed. PMID- 2270467 TI - Determination of total mercury concentration in wastewater by continuous microflow analysis with cold vapor atomic absorption spectrometry. PMID- 2270468 TI - The relationship between mercury from dental amalgam and the cardiovascular system. AB - The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of cardiovascular disorders. Comparisons between subjects with and without amalgam showed amalgam-bearing subjects had significantly higher blood pressure, lower heart rate, lower hemoglobin, and lower hematocrit. Hemoglobin, hematocrit, and red blood cells were significantly lower when correlated to increased levels of urine mercury. The amalgam subjects had a greater incidence of chest pains, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning. The data suggest that inorganic mercury poisoning from dental amalgam does affect the cardiovascular system. PMID- 2270469 TI - Levels of selenium and antioxidative enzymes following occupational exposure to inorganic mercury. AB - Levels of selenium and mercury in blood and urine were analysed in 37 male workers exposed to elemental mercury vapour in a chloralkali plant and in 39 unexposed controls of the same age. Mean urinary Hg was 223 nmol l-1 (15 nmol/mmol creatinine) in the exposed group and 26 nmol l-1 (2.0 nmol/mmol creatinine) in the controls. Mean blood and plasma Hg levels were 46 and 36 nmol l-1, respectively, in the exposed group, as compared with 17 and 7 nmol l-1 in the controls. The concentrations of Se in plasma and erythrocytes did not differ between the two groups. Urinary Se levels were, however, slightly but significantly lower in the exposed group (median values 23 vs 29 nmol/mmol creatinine), and there was a negative correlation between urinary Se and plasma Hg in the exposed group. This may be due to a retention of Se in the kidneys. In a subgroup of exposed workers and controls, glutathione peroxidase, superoxide dismutase and catalase were also analysed. No differences were found between the groups with respect to these antioxidative enzymes. The effect on Se status of moderate Hg exposure seems to be of minor clinical importance. PMID- 2270470 TI - Measurements of the equilibrium factor for 222Rn daughters in dwellings in India. AB - As part of an ongoing project to assess the population dose from indoor radon and its daughters in India, a set of parallel measurements was made in more than 150 houses of different types to estimate indoor radon and progeny levels. Time integrated solid state nuclear track detectors were employed for the measurement of radon concentration and potential alpha energy exposure level. From these values the equilibrium factor (F) between radon and its progeny was estimated for each house. An average F value of 0.39 was obtained. PMID- 2270471 TI - Investigation of used synthetic lubricants by computerized gas chromatography/mass spectrometry. AB - The chemical fractions of a used, synthetic lubricating oil for petrol engines were separated by flash chromatography on a silica gel column using variable mixtures of hexane/chloroform as eluents. The products extracted in the most polar fraction were separated by gas chromatography and then analyzed by computerized mass spectrometry. The analytical method used allowed the identification, among the various compounds, of a family of tetrahydropyran homologues with an aminic chain, phthalates, thiophene and pyridine derivatives. The presence of these structures, some of which are of toxicological interest, was also shown by infrared spectra. PMID- 2270472 TI - Small mammals as biological indicators of radioactive contamination of the environment. AB - An investigation was carried out in Sweden aimed at studying the contamination of small mammals (orders Rodentia and Insectivora) following the Chernobyl accident. The animals were captured in three differently contaminated areas in Sweden and, for control, in an area with negligible fallout. The results obtained show that the activity in the captured animals was correlated with surface deposition. The differences between the species investigated and the influence of feeding habits on the contamination levels are discussed. PMID- 2270473 TI - Maternal plasma concentrations of magnesium, calcium, zinc and copper in normal and pathological pregnancies. AB - In this study, plasma levels of magnesium, calcium, zinc and copper were simultaneously determined in pregnancies complicated by either abortion, intrauterine growth retardation (IUGR), diabetes or EPH (edema, proteinuria, hypertension) gestosis. The levels of the four cations in non-pregnant women and in healthy, pregnant women were also determined. Compared with controls, a significant decrease in magnesium, with increase of the Ca/Mg ratio, was found in spontaneous abortions, but not when patients had a successful continuation of pregnancy. In EPH gestosis, total calcium was reduced, with a significant decrease of the plasma Ca/Mg ratio. A slight, but significant, increase in plasma zinc was observed in women affected by either diabetes or IUGR, probably as a result of reduced zinc uptake by the fetus. In addition, higher copper levels were found in the pathologies studied, with the exception of missed abortions. The possible role of an altered Ca/Mg ratio homeostasis in relation to gestational pathologies is discussed. PMID- 2270475 TI - Biomedical funding: the eternal "crisis". PMID- 2270474 TI - Carcinogens and human health: Part 1. PMID- 2270476 TI - Slow going for blood substitutes. PMID- 2270477 TI - Immune mystery revealed: how MHC meets antigen. PMID- 2270478 TI - Breast cancer: two steps closer to understanding. PMID- 2270479 TI - Pinning down sequencing costs. PMID- 2270480 TI - A mechanism for social selection and successful altruism. AB - Within the framework of neo-Darwinism, with its focus on fitness, it has been hard to account for altruism behavior that reduces the fitness of the altruist but increases average fitness in society. Many population biologists argue that, except for altruism to close relatives, human behavior that appears to be altruistic amounts to reciprocal altruism, behavior undertaken with an expectation of reciprocation, hence incurring no net cost to fitness. Herein is proposed a simple and robust mechanism, based on human docility and bounded rationality that can account for the evolutionary success of genuinely altruistic behavior. Because docility-receptivity to social influence-contributes greatly to fitness in the human species, it will be positively selected. As a consequence, society can impose a "tax" on the gross benefits gained by individuals from docility by inducing docile individuals to engage in altruistic behaviors. Limits on rationality in the face of environmental complexity prevent the individual from avoiding this "tax." An upper bound is imposed on altruism by the condition that there must remain a net fitness advantage for docile behavior after the cost to the individual of altruism has been deducted. PMID- 2270481 TI - Mechanisms in the cycle of violence. AB - Two questions concerning the effect of physical abuse in early childhood on the child's development of aggressive behavior are the focus of this article. The first is whether abuse per se has deleterious effects. In earlier studies, in which samples were nonrepresentative and family ecological factors (such as poverty, marital violence, and family instability) and child biological variables (such as early health problems and temperament) were ignored, findings have been ambiguous. Results from a prospective study of a representative sample of 309 children indicated that physical abuse is indeed a risk factor for later aggressive behavior even when the other ecological and biological factors are known. The second question concerns the processes by which antisocial development occurs in abused children. Abused children tended to acquire deviant patterns of processing social information, and these may mediate the development of aggressive behavior. PMID- 2270482 TI - Linkage of early-onset familial breast cancer to chromosome 17q21. AB - Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region. PMID- 2270483 TI - Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. AB - A heparin binding mitogenic protein isolated from bovine uterus shares NH2 terminal amino acid sequence with a protein isolated from newborn rat brain. The cDNA's of the bovine, human, and rat genes have been isolated and encode extraordinarily conserved proteins unrelated to known growth or neurotrophic factors, although identity of nearly 50 percent has been found with the predicted sequence of a retinoic acid induced transcript in differentiating mouse embryonal carcinoma cells. Lysates of COS-7 cells transiently expressing this protein were mitogenic for NRK cells and initiated neurite outgrowth from mixed cultures of embryonic rat brain cells. RNA transcripts encoding this protein were widely distributed in tissues and were developmentally regulated. This protein, previously designated as heparin binding growth factor (HBGF)-8, is now renamed pleiotrophin (PTN) to reflect its diverse activities. PTN may be the first member of a family of developmentally regulated cytokines. PMID- 2270484 TI - Characterization of "peak E," a novel amino acid associated with eosinophilia myalgia syndrome. AB - Epidemiologic studies strongly associate eosinophilia-myalgia syndrome (EMS) with ingestion of tryptophan containing a contaminant ("peak E"). Prior reports have suggested that peak E is the di-tryptophan N alpha-animal of acetaldehyde. Spectral and chemical studies now demonstrate that peak E is 1,1' ethylidenebis[tryptophan]. This novel amino acid may be the etiological agent responsible for EMS, or it may be a marker of a still unidentified causal agent. PMID- 2270485 TI - Zinc mediation of the binding of human growth hormone to the human prolactin receptor. AB - Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH. PMID- 2270486 TI - Inheritance of proliferative breast disease in breast cancer kindreds. AB - Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer. PMID- 2270487 TI - Transport protein genes in the murine MHC: possible implications for antigen processing. AB - T lymphocyte activation requires recognition by the T cell of peptide fragments of foreign antigen bound to a self major histocompatibility complex (MHC) molecule. Genetic evidence suggests that part of the class II region of the MHC influences the expression, in trans, of MHC class I antigens on the cell surface, by regulating the availability of peptides that bind to and stabilize the class I molecule. Two closely related genes in this region, HAM1 and HAM2, were cloned and had sequence similarities to a superfamily of genes involved in the ATP dependent transport of a variety of substrates across cell membranes. Thus, these MHC-linked transport protein genes may be involved in transporting antigen, or peptide fragments thereof, from the cytoplasm into a membrane-bounded compartment containing newly synthesized MHC molecules. PMID- 2270488 TI - Hemolin: an insect-immune protein belonging to the immunoglobulin superfamily. AB - Insects have an efficient defense system against infections. Their antibacterial immune proteins have been well characterized. However, the molecular mechanisms by which insects recognize foreignness are not yet known. Data are presented showing that hemolin (previously named P4), a bacteria-inducible hemolymph protein of the giant silk moth Hyalophora cecropia, belongs to the immunoglobulin superfamily. Functional analyses indicate that hemolin is one of the first hemolymph components to bind to the bacterial surface, taking part in a protein complex formation that is likely to initiate the immune response. PMID- 2270489 TI - A new arbovirus from Aedes albopictus, an Asian mosquito established in the United States. AB - Ten strains of a new arbovirus belonging to the Bunyamwera group (Bunyaviridae) were recovered from field-collected Aedes albopictus mosquitoes in Potosi, Missouri. This evidence indicates that this species may serve as an arbovirus vector in the United States. The urban-suburban distribution, aggressive biting behavior, and broad viral susceptibility of Ae. albopictus may lead to the transmission of viruses of known public health importance and perhaps of viruses hitherto not transmitted to humans because of the feeding pattern of their usual vectors. PMID- 2270490 TI - [The biology of bones and of bone fracture healing]. AB - For the treatment of fractures several systems are available. Biological and biomechanical aspects have to be considered in order to obtain an optimal final result. The vascular supply of the intact and of the fractured bone is reviewed. The role of the fracture hematoma with a low pO2 and a pH below the physiological range are discussed. In bone remodelling tension forces and cyclic loading are important factors in resorption and regeneration. The influence of the periosteum in bone healing after internal fixation is described. PMID- 2270491 TI - [Indications for interlocking nailing]. AB - For closed diaphyseal fractures of femur and tibia in adults, medullary nailing with interlocking nails has become the treatment of choice. Their use has been extended to certain intraarticular fractures in combination with shaft fractures, compound fractures with low-grade wound contamination, malunion, non-union and pathologic fractures. Locked nailing should be performed as a closed procedure, and callus bone healing should be expected. Fracture hematoma, drill debris and preservation of periosteal circulation are of particular relevance in achieving this. Dynamization by removal of the locking screw(s) opposite the fracture site accelerates the transformation and ossification of early fixation callus. PMID- 2270492 TI - [Correction osteotomy and stabilization with the interlocking nail]. AB - Compression and angle plates fitted after corrective osteotomies for congenital or post-traumatic bony malalignment entail the disadvantage that a longer period of non-weight-bearing is needed before consolidation. This is in contrast to the advantages of medullary nailing with interlocking nails in dynamic and static applications, which allow early weight-bearing. The interlocking nail can be used after osteotomies to correct derotation and axial malalignment, but also after lengthening and shortening osteotomies, which we perform both as open procedures and as closed procedures with the aid of the Kuntscher saw. PMID- 2270493 TI - Mechanics of intramedullary nails for femoral fractures. AB - Biomechanical studies were carried out to assess the function and performance of intramedullary (IM) nails for femoral fractures. An appropriately sized femoral IM nail with a radius of curvature of about 109 cm would most closely match the anterior bow of most human femora. A number of parameters can interact to result in bursting of the femur during insertion of the nail. These include mismatch in curvature of the nail and femur, high stiffness in bending, and poor location of the starting hole. An anatomic starting position for the IM nail is just medial to the greater trochanter and anterior to the pyriformis recess. Moving anterior to the midline of the femur significantly increases the potential for bursting the femur during insertion of the nail. Other factors can decrease the force of insertion of the IM nail in the femur. These include overreaming, shortening the axial length of the fracture component, and use of a nail of lower bending rigidity. IM-nail-fixed femoral shaft fractures with locking bolts can be expected to have about 75% the rigidity of the intact femur in bending and can support about 400% of normal body weight (= 70 kg). Slotted IM nail/femur constructs have only about 3% the rigidity of the intact femur in torsion, while an unslotted (closed) section implant produces constructs with about 50% the rigidity. The distal locking bolts increase the torsional rigidity and maximum axial load capacity of the construct, and reduce the potential for shortening and the residual deformation upon release of a torsional load. Two distal bolts reduce the toggle of the nail in the femoral shaft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270494 TI - [The interlocking nail for long comminuted and compound fractures of the femur and tibia. Technique and results]. AB - Interlocking nailing is presented as an optimal method for the treatment of fractures of femur and tibia, which are complicated because of the length of these bones. Cases from the literature and cases treated by the authors gave a total of 208 fractures of the femur and 158 fractures of the tibia (comminuted fractures and fractures "a deux etages"). There is a low complication rate as a closed procedure was applied whenever possible. In the femur the nail fractured in eight cases (3.9%), while in seven cases infection was observed (3.5%) and in three cases pseudarthrosis. Following interlocking nailing of the tibia we found deviation of the axis by greater than 5 degrees in eight cases (5%) of 158, including 44 open fractures. Fracture of the nail occurred in one case (0.6%), and we observed six cases of infection (3.8%) and one of pseudarthrosis (0.6%). PMID- 2270495 TI - [The treatment of proximal femoral fractures using the interlocking nail]. AB - The good result hoped for with interlocking nailing of the proximal part of the femoral shaft is only possible when precise diagnosis is of the fracture form is made with reference to informative X-rays and a meticulous operative technique is observed. Therefore, positioning of the patient on an extension table, the repositioning of the bone, the choice of the insertion point for the nail, and careful drilling are of the utmost important. All follow-up examinations conducted in 42 patients, we found good or very good results in 32 cases, satisfactory results in 7, and poor results in 3. PMID- 2270496 TI - [Interlocking nailing of distal femoral fractures. Technique and results]. AB - Treatment with interlocking nails is sufficient for fractures at the distal diaphysis and the distal methaphyseal region of the femur. Fractures associated with intracondylar fissures can be treated with an interlocking nail only in isolated cases. This paper gives a report on 47 cases and compares two series. The complications observed were: infection (4.25%); fracture of nail (4.25%); and deviation of axis (12.08%). We didn't observe pseudarthrosis in any of these patients. Bone healing occurred in all cases. PMID- 2270497 TI - [Interlocking nailing of fractures of the proximal tibial shaft]. AB - The anatomic construction of the proximal part of the tibial shaft induces high ventral traction forces. Consequently, the mechanical requirements for stability of any internal fixation system are also high. Therefore, interlocking nailing of fractures of the proximal tibial shaft demands a meticulous operative technique as far as the incision, implantation of the nail and the final interlocking are concerned. Typical complications in this area are axis deviation, loosening of the interlocking screws and delayed union. Particular attention should be paid to the risk of hitherto unnoticed fissures ascending into the tibial head. PMID- 2270498 TI - [Results of interlocking nailing of distal tibial fractures]. AB - Between 1982 and 1989, 117 fractures of the distal part of the lower leg were surgically treated in the Trauma Clinic belonging to the employers' liability insurance company in Frankfurt/Main. A follow-up examination of 85 of these patients, based on X-ray series, clinical reports, and insurance files, shows the functional results. Because of the high proportion of good to excellent results (95.4%), we consider fracture of the distal tibia a good indication for interlocking nailing, even from the aspect of the borderline indication of fracture in the fifth sixth. In open fractures of the distal part of the lower leg we consider the change of method from primary stabilization with external fixation to secondary interlocking nailing an appropriate procedure. The methods presented for internal fixation of fractures of the distal tibia by interlocking nailing allow early partial and full weight-bearing with the stability needed for exercising. PMID- 2270499 TI - Biosocial models of adolescent problem behaviors. AB - This paper develops a biosocial model of adolescent age-graded norm violations ("problem behaviors"), combining a traditional social control model with a biological model using steroid hormones. Subjects were 101 white boys drawn from the 8th-, 9th-, and 10th-grade rosters of selected public schools, and ranging in age from 13 to 16. Subjects completed self-administered questionnaires and provided blood samples which were assayed for the behaviorally relevant hormones. Boys' problem behavior shows strong hormone effects. Social and biological variables have both additive and indirect effects. Using a biosocial model leads to conclusions which are different from those which would have been drawn from the sociological model alone. PMID- 2270500 TI - Individual fertility rate: a new individual fertility measure for small populations. AB - Fertility measurement in small preindustrial societies is hampered by small numbers and the lack of some essential data. Most measures of fertility are collective and require large enough populations to permit grouped data analysis. Existing individual measures of fertility are often unsatisfactory. This paper presents a new measure of individual fertility, the Individual Fertility Rate (IFR), which is constructed by dividing parity by reproductive span in years and multiplying the product by 100. The result is a number which may be used as a dependent individual or cumulative variable to study the effects of health and socioeconomic factors on fertility. PMID- 2270501 TI - Differential mortality by ethnicity and nativity: foreign- and native-born Irish, Italians, and Jews in New York City, 1979-1981. AB - This paper compares the mortality experience of foreign- and native-born Irish, Italians, and Jews in New York City in 1979-81. In most cases, denominator data were not available, so proportional mortality analysis was used. An estimation procedure was undertaken to show the degree to which standardized proportional mortality ratios approximate relative standardized mortality measures. Major and lifestyle-related causes of death were examined, as were specific sites of cancer. While no consistent pattern merged which related nativity or ethnicity to the relative distribution of mortality, it does appear that the intra-ethnic patterns of the Irish group were unique relative to those of the Italian and Jewish groups. Overall, this study suggests a number of interesting relationships between ethnicity, nativity, and the distribution of mortality by cause. PMID- 2270502 TI - Postpartum sexual abstinence, breastfeeding, and childspacing, among Yoruba women in urban Nigeria. AB - This paper examines the extent to which the traditional practice of sexual abstinence during lactation has broken down among Yoruba women residents in urban areas. The first major finding is that there is a gradual erosion of the tradition, and the dominant factors of modernization are education of the woman and the use of contraception. The second major finding is that the breakdown of postpartum sexual taboos has statistically significant negative consequences on duration of lactation, although the negative impact of woman's education is greater. The third major finding is that duration of breastfeeding reduces birth interval significantly only when it is less than 15 months, and that both durations of breastfeeding and birth intervals have declined over time. The first two findings suggest further reductions in the proportion of women who abstain from sexual relations during lactation and in durations of breastfeeding as more women become more educated. Significant declines in birth intervals may follow soon after. PMID- 2270503 TI - Assortative mating in monozygotic twins. AB - This study investigated assortative mating in a series of monozygotic twins in terms of anthropometric variables. Initially the twins were analyzed independent of each other, and the results showed fairly clear homogamy among female MZ twins and their spouses, after correcting for age. Further, when stature was partialled out, several anthropometric measures remained significantly correlated. The results for male MZ twins and their spouses were not nearly so clear-cut. A second analysis treated the co-twins together, and once again, the female MZ sets tended to show assortative mate choice for stature while the male MZ twins/spouses were not significantly correlated. A follow-up analysis investigated whether husbands of the female twins were correlated to each other, and negative results were found for all of the 46 anthropometric variables. An apparent contradiction was resolved in the case of stature by regressing spouse stature against that of the co-twins. It was found that although each of the twins was assortatively mating, one member of the twin set consistently married a taller husband, but the difference was not constant. This had the effect of producing divergent regression lines. PMID- 2270504 TI - Differential rates of secular increase of five major primary abilities. AB - A number of studies have shown that mean intelligence levels have been increasing at a rate of around 3 IQ points per decade during the last half-century. This paper presents data for cohorts of 9-11 year olds in Northern Ireland tested in 1978 and 1988 and shows that the rates of increase differ markedly for different primary abilities. Verbal comprehension has shown virtually no increase, while there have been large increases in spatial relations and perceptual speed. Moderate increases have taken place in the numerical and reasoning primaries. The results are interpreted as supporting a nutrition theory of the secular increases in intelligence. PMID- 2270506 TI - Intra-ethnic and inter-ethnic marriage and divorce in Hawaii. AB - A comparison of intra- and inter-ethnic divorce rates in Hawaii showed that inter ethnic marriages resulted in a higher proportion of divorces than did intra ethnic marriages when the marriage data used had to do with all marriages occurring in Hawaii. However, a sizeable portion of marriages in Hawaii are of nonresidents who, if they divorce, probably divorce elsewhere. Nonresident marriages are chiefly intra-ethnic marriages of Caucasians. When examining the proportions of divorces to resident marriages, within-group marriages are more at risk than inter-ethnic marriages. As in prior research, persons who marry members of other racial/ethnic groups tend to marry persons from groups with income levels similar to their own. As in previous reports, some cross-ethnic combinations appeared more at risk for divorce than did others. Group income appeared to be a predictor of risk. When considering only resident marriages as related to divorces, those marriages in which the bride was from a higher income group than the groom were at a significantly greater risk for divorce than marriage in which the bride came from an income group lower than that of the groom. PMID- 2270505 TI - Female fecundity in highland Papua New Guinea. AB - Demographers often assume that interpopulation variation in birth spacing is attributable primarily to behavioral differences (e.g., in breastfeeding, coital frequency, or contraceptive practice), and that the contribution of physiological factors is negligible. This assumption may be correct, but it should be tested, especially in light of recent evidence that there may be more variation in ovarian function among human populations than was previously believed. In this paper, we apply a stochastic model of the determinants of fecundability (the monthly probability of conception) to endocrinological data collected among the Gainj, a tribal population in highland Papua New Guinea. Based on previous research, the Gainj are known to have age patterns of ovarian function that differ markedly from the Western norms. When account is taken of the late menarche, early menopause, and long ovarian cycles that appear to characterize Gainj women, mean apparent fecundability across the female reproductive span is reduced by about 27 per cent (from 0.316 to 0.235), and the mean waiting time to next apparent conception is increased by just over one month. Thus, despite the fact that Gainj women differ from Western women with respect to reproductive physiology by as much as or more than any other known population, the demographic impact of these differences appears to be slight. PMID- 2270507 TI - More on the determinants of the fertility transition. AB - The economic approach to fertility is an application of the economics theory of consumer behavior. It is assumed that consumers of children are utility maximizers with stable preferences over time. Thus, changes in fertility are related to changes in household income and the "price" of children. One concern in this approach is that demographic changes are a product of changes in tastes rather than exogenous changes in economic factors such as the earning ability of women. In this paper, the effect of economic variables on the demand for children in the United States in 1950, 1960, 1970, and 1980 is examined. Support is provided for the hypothesis that the earning ability of women is an important determinant of fertility. PMID- 2270508 TI - A causal approach to the study of fertility and familism. AB - This paper tests, within the framework of LISREL, the causal structures of fertility using data from the 1973-74 Growth of Alberta Family Study (GAFS) of women aged 18-44 who are currently married or living common-law. Differential fertility among two groups of women classified by nativity also are examined. The women's background characteristics (e.g., age, religiosity, and education) are viewed as exogenous variables. The endogenous variables are familism and expected family size; familism is designated as an intermediate variable in the model, linking demographic and socioeconomic (including cultural) factors to fertility, The results indicate that familism acts as an important variable explaining fertility, particularly, among foreign-born women. The study confirms and extends earlier research findings that religiosity and education influence couples' fertility, the former positively and the latter negatively. PMID- 2270509 TI - Assessing the reproductive behavior of on- and off-reservation American Indian females: characteristics of two groups in Montana. AB - Only limited fertility and general reproductive health data exist on American Indians. Using data from the 1987 Montana American Indian Health Risk Assessment, we found that the fertility of American Indians in Great Falls and on the Blackfeet Reservation was similar to blacks in the U.S. and relatively high when compared with fertility of whites in the United States. The influence of the direct determinants of fertility (nuptiality, contraceptive use, and lactation) was very different for the populations examined in this study. Great Falls American Indians and the U.S. black population were similar regarding age at first sexual intercourse (very young), breastfeeding (low prevalence and short duration), planning status of pregnancies (high unplanned), and contraceptive use (only moderate use). In contrast, Blackfeet women on the reservation and the U.S. white population married relatively late, had very high contraceptive use, used effective methods of contraception, and had moderately high levels of breastfeeding. However, Blackfeet fertility was much higher than that of whites. Three interrelated reasons are suggested as possible explanations. Blackfeet couples either wanted high fertility, were relatively poor users of family planning methods, or used less effective methods until they had exceeded their desired family size after which time they turned to sterilization. These finds raise numerous questions concerning the social and economic factors that may account for these group similarities and differences. Further studies with much larger data sets are needed to address these issues adequately. PMID- 2270510 TI - Family networks in prenatal and postnatal health. AB - This paper examines the effects of kin access on prenatal health practices, birth outcome, and postnatal health practice for infants born to black and white mothers ages 21 to 28 in the U.S. during 1984-86. The data used for this research were compiled from three sources: (1) The National Longitudinal Survey of Youth; (2) The Children of the National Longitudinal Survey of Youth; (3) special kin access data files, which were created specifically for this study. Logistic regression procedures are used to assess the effects of kin proximity, maternal grandmother proximity, and presence of the child's father on health practices (N = 1,030) and birth outcome (N = 1,385), controlling for the mother's educational attainment, work experience, poverty, presence of the child's father, and birth order of the child. We find no evidence supporting the notion that kin access positively affects the prenatal and postnatal health practices of young mothers. The results suggest that young mothers who reside with their mothers or other adult kin, and those who are in close proximity to them, are no more likely to seek prenatal care during the first trimester, or to avoid smoking or drinking during pregnancy. Mothers who live with a sexual partner or husband are, however, somewhat more likely to seek prenatal care and to avoid alcohol use during pregnancy. Closer kin access is associated with a lower probability of breastfeeding. These results suggest that it will not be adequate to rely on kin networks or kin assistance to improve the prospect of healthy birth outcomes. PMID- 2270511 TI - [Legal regulations of medical activities]. AB - The article contains an analysis of some provisions of the existing health legislation. At the same time a short statement is given of civil and criminal judicial procedures which make provisions for some professional duties of physicians. It is supposed that the performance of these duties would require additional legal knowledge for example, in the field of hereditary law. PMID- 2270512 TI - [Methodical approaches to the elaboration and application of estimated norms of time in physical examinations]. AB - The statement of general principles, the methodology of working out the estimated norms of time for functional examinations would promote the proper understanding of amount and contents of work done by medical personnel utilizing these norms in the performance of departments of functional diagnosis which is necessary for valid planning and management of these diagnostic units. PMID- 2270513 TI - [Regional evaluation of the state of population health protection]. AB - The paper contains theoretical provisions and methods of information supply of public health programmes under conditions of the improvement of management and broadening of independence of local public health bodies. Emphasis is being placed on the role of fundamental studies in the formation of population's health and methods of multifactor analysis permitting to identify regional health problems and to substantiate priority measures. There is a discussion of the system of health indices and activities of public health bodies and institutions which are to be used in economic methods of management along with the evaluation of health programmes efficiency according to the ultimate results. Periodic probe investigations of health problems and the degree of population's satisfaction with health care contribute considerably to this practice. The materials of the complex study of population's health in connection with the 1989 census of the population in many respects meet these requirements and the paper provides ways for the organization and cooperation with the chairs of social hygiene while carrying out this large-scale study. PMID- 2270514 TI - [Problems in improving information supply in the public health administration]. AB - F. G. Grigoriev (Soviet Public Health, 1989, No. 2, p. 31-36) raised an issue of the necessity to considerably reduce the amount of annual statistical reporting of curative and preventive institutions. The preparation and drawing up of such a report in its present form require an unjustified lot of time and means. But it is advisable to broaden this task and to solve it as a problem of optimizing the information supply of public health management with allowance made for its present state and prospects of development for the nearest 8-10 years. The problem could be solved by rationally reducing the number of insufficiently informative and duplicating forms of reporting, sections (tables) of annual statistical reports and by a wider introduction of paperless informatics system. PMID- 2270516 TI - [Dynamics and structure of morbidity with temporary disability among oil-industry workers in Western Siberia]. AB - The analysis of disease-caused temporary disability among oil-industry workers in Western Siberia permitted to reveal its major trends and the dependence of the level, severity and pattern of disability on the age-and-sex structure and length of service. The level of disease-caused temporary disability is being determined at industrial enterprises which necessitates the in-depth study of the given populations of oil-industry workers. PMID- 2270515 TI - [Role of the family in the rehabilitation of crippled children]. AB - The article contains the findings of a socio-hygienic survey of families with crippled children suffering from cerebral palsy. A description is made of the procedure for conducting a survey based of International Classification of disorders, lowering of ability to work, social inadequacy and methods of factor analysis. The main socio-hygienic factors which characterize the families with crippled children and influence the process of medico-social rehabilitation of children were obtained on the basis of factor analysis. PMID- 2270517 TI - [Features of morbidity of children starting at the age of 6 years to learn at preschool institutions]. AB - During two academic years the morbidity of 300 children attending preschool institutions starting from the age of six were studied. The study indicated the adverse educational and mental effect on six years old schoolchildren which was manifested by the rise of morbidity during the second half of the academic year, increase in the number of morphofunctional dysfunctions of some organs and systems by the end of the academic year. Suggestions are made of curative and health-promoting activities aimed at health protection and promotion and reduction of morbidity among children. PMID- 2270518 TI - [Evaluation of factors influencing the formation of personal qualities in nurses]. AB - The article provides a socio-psychological evaluation of factors influencing the formation of personal qualities of nurses. For the purpose of screening diagnosis of professionally conditioned deformation of personal qualities the following semantic variables were chosen: a capacity for initiative, discipline, honesty, sympathy, communicativeness, discretion. The influence of nurses' age, specialization, place of work, family status on self-evaluations is traced. Factors are identified which influence the working stability of medium-level personnel under conditions of major curative and preventive institutions. PMID- 2270519 TI - [Improving the information supply of a polyclinic]. AB - The article provides a description of a new statistical information supply of a polyclinic based on a special registration form--"An ambulatory patient coupon". The peculiarities and advantages of this document are demonstrated, some findings are provided. PMID- 2270520 TI - [Experience in training subinterns in theory and practice of prevention]. AB - 2380 workers have been screened and provided with findings of their health status and recommendations with regard to identified risk factors for chronic non communicable diseases (CNCD) and for CNCD themselves. The study of the influence of the training cycle on the attitude of students-subinterns toward preventive part of physician activity indicated the increase in the level of knowledge on prevention issues of CNCD and recognition of the necessity to include preventive measures into the activity of district physician. The experience gained in joint activities of the All-Union Research Centre for Industrial Medicine, The USSR Ministry of Health, and the Chair of out-patient medicine of the Kalinin Medical Institute suggests the need for improving the existing system of students training. PMID- 2270521 TI - [Differentiated educational programs on AIDS prevention at the U.S. schools (review)]. PMID- 2270522 TI - [Concerning G. A. Alekseev's articles "Physicians and traditional healers of Volga Bulgaria in the 9th-13th centuries" and "Medical science in middle lands along the Volga in the period of feudalism"]. PMID- 2270523 TI - [Definition of the terms "prevention" and "treatment"]. PMID- 2270524 TI - [200 years of public health in the Nikolaev Region]. PMID- 2270525 TI - [V. I. Rudnev--author of the Russian translation of the "Hippocrates doctrine"]. PMID- 2270526 TI - [Kh. G. Rakovskii's activities at the People's Commissariat of Health of the Russian R.S.F.R (1934-1937)]. PMID- 2270527 TI - [Additional materials on S. S. Iudin]. PMID- 2270528 TI - The founding of the International Society on Thrombosis and Haemostasis: how it came about. PMID- 2270529 TI - Does increased platelet aggregation have a prognostic value in the deterioration of background diabetic retinopathy? The Damad Study Group. AB - Many case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy. PMID- 2270530 TI - The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study. AB - This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population. PMID- 2270531 TI - Subcutaneous vs intravenous heparin in the treatment of deep venous thrombosis--a randomized clinical trial. AB - 271 patients with acute symptomatic deep venous thrombosis of lower limbs, confirmed by strain-gauge plethysmography and/or venography, were randomly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6-10 days. Heparin dosage was adjusted to maintain activated partial thromboplastin time values (Thrombofax reagent) at 1.3 1.9 times the basal ones. Strain-gauge plethysmography was repeated at the end of heparin treatment, and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications. In the intravenous group, Maximal Venous Outflow (MVO) increased from 20.8 +/- 12.8 to 28.4 +/- 17.5 ml/min per 100 ml of tissue and Venous Capacitance (VC) from 1.39 +/- 0.92 to 1.94 +/- 1.0 ml/100 ml of tissue (mean +/- SD). In the subcutaneous group, MVO increased from 21.0 +/- 12.7 to 27.5 +/- 18.1 and VC from 1.60 +/- 0.86 to 2.06 +/- 1.0. The median improvement of MVO and VC were 22% and 36% respectively in the IV group and 20% and 24% in the SC group. Clinical pulmonary embolism occurred in 2 patients in the intravenous group (1 fatal) and in 4 in the subcutaneous group (1 fatal). 9 major bleeding complications occurred in the intravenous group (1 fatal) and 5 in the subcutaneous group (1 fatal). The differences were not significant at the statistical analysis. The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis. To the same conclusion points an overview of the seven randomized trials which compared these treatment modalities. PMID- 2270532 TI - Isolation and characterization of a coagulation factor Xa inhibitor from black fly salivary glands. AB - We have discovered and characterized a novel coagulation factor Xa inhibitor from the salivary gland of the black fly, Simulium vittatum. Salivary glands were surgically dissected from the flies and a crude salivary gland extract was tested for inhibition of a number of coagulation assays. The gland extract inhibited both thrombin and factor Xa. To purify further the factor Xa inhibitor, a factor Xa affinity column was utilized. Final purification of the black fly factor Xa inhibitor was achieved by reverse-phase C8 microbore high pressure liquid chromatography. Inhibition of factor Xa was nearly stoichiometric by the purified inhibitor with no inhibitor of thrombin detected. SDS-polyacrylamide gel electrophoresis indicated the inhibitor had a molecular weight of 18,000 and sequence analysis of the inhibitor revealed a blocked amino terminus. These data indicate that the blood-sucking black fly has evolved a highly potent inhibitor of mammalian coagulation factor Xa to disrupt its host normal hemostatic clotting mechanisms. PMID- 2270533 TI - Human pharmacokinetics and pharmacodynamics of MF 701 dermatan sulfate administered by continuous intravenous infusion. AB - The pharmacokinetics and haemostatic effects of MF 701 dermatan sulfate (DS) administered by i.v. infusion were studied in 11 healthy volunteers. Each subject received 0.6 mg kg-1 h-1 MF 701 for 10 h. DS plasma concentrations were measured by a chromogenic assay based on the catalysis of thrombin inhibition by HCII. DS plasma levels followed a single compartment pharmacokinetic model, with a half life of 1.28 +/- 0.46 h, a plasma clearance of 2.75 +/- 0.46 l/h and a volume of distribution of 4.92 +/- 1.36 1 (means +/- SD). Steady-state was reached 3 to 6 h after infusion started. The maximal DS plasma concentration was 16.4 +/- 5.7 micrograms/ml. Maximal APTT prolongation over pre-infusion values was 42 +/- 7%; TCT performed with bovine and human thrombin was prolonged by 16 +/- 7% and 83 +/ 35% respectively. No anti-IIa or anti-Xa activities were detected by chromogenic tests. The treatment was well tolerated. The pharmacokinetics of MF 701 infusion are consistent with those previously described after i.v. bolus administration. The infusion of MF 701 allows fast achievement and steady maintenance of elevated DS plasma concentrations. PMID- 2270534 TI - A collaborative study to establish the second international standard for streptokinase. AB - An International Standard for Streptokinase--Streptodornase (62/7) has been used to calibrate high purity clinical batches of SK since 1965. An international collaborative study, involving six laboratories, was undertaken to replace this standard with a high purity standard for SK. Two candidate preparations (88/826 and 88/824) were compared by a clot lysis assay with the current standard (62/7). Potencies of 671 i.u. and 461 i.u. were established for preparations A (88/826) and B (88/824), respectively. Either preparation appeared suitable to serve as a standard for SK. However, each ampoule of preparation A (88/826) contains a more appropriate amount of SK activity for potency testing, and is therefore preferred. Accelerated degradation tests indicate that preparation A (88/826) is very stable. The high purity streptokinase preparation, coded 88/826, has been established by the World Health Organisation as the 2nd International Standard for Streptokinase, with an assigned potency of 700 i.u. per ampoule. PMID- 2270535 TI - Heparin effect on bone density. AB - In order to provide estimates of the risks of symptomatic osteoporosis and reduced bone density in premenopausal women treated with long-term (greater than 1 month) heparin therapy, we evaluated a cohort of 61 consecutive premenopausal women previously treated with long-term heparin (cases) and a group of controls matched for age, parity and duration between the last pregnancy and evaluation. All patients underwent dual photon absorptiometry of the lumbar spine and single photon absorptiometry of the wrist and most cases underwent plain lateral radiography of the thoracolumbar spine in order to exclude silent fractures. Although none of the cases suffered symptomatic fractures (0 of 61, 95% confidence intervals 0.0 to 5.9%), there was a significantly greater proportion of cases than controls with bone density below our pre-defined levels. The long term implications of our findings are uncertain but because it is possible that the reduction in bone density predisposes women to fractures, this potential risk should be considered when treating women with long-term heparin. PMID- 2270536 TI - Potentiation of the antithrombotic action of dermatan sulphate by small amounts of heparin. AB - We have examined the effect in impairing thrombus formation of a preparation of dermatan sulphate (DS) alone and DS plus small amounts of unfractionated heparin (UFH). In rabbits given a dose of 150 micrograms/kg of DS alone, there was minimal reduction in serum-induced stasis thrombosis (Wessler model), with an overall score of 92.5% (100% = no impairment of thrombus formation). When the same dose of DS containing UFH was given (two different subgroups given DS containing 0.25 and 2.5% heparin by dry weight, respectively), the overall thrombus score was reduced to 60% (P less than 0.003), with no significant difference between the two subgroups. To achieve a comparable result with DS alone, a dose of 1 mg/kg was required. We conclude that very small amounts of UFH significantly enhance the antithrombotic action of DS, by a mechanism that has yet to be determined. PMID- 2270537 TI - Venostasis but not DDAVP infusion provokes the plasma fibronectin increase. AB - Plasma fibronectin (pFN), von Willebrand factor antigen (vWf:Ag), factor VIII procoagulant activity, fibrinogen, euglobulin lysis time (ELT) and hematocrit were determined in healthy blood donors before and after venostasis as well as after intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP). Both venostasis and DDAVP provoked an increase in vWf:Ag and shortening in the ELT. In contrast, venostasis only but not DDAVP induced an increase in pFN levels which was statistically significant with and without correction for a concomitant hematocrit increment. The results indicate that there is a distinct difference in the patterns of venostasis and DDAVP mediated release of proteins from the vessel wall. PMID- 2270538 TI - Point mutations in four hemophilia B patients from China. AB - Point mutations in factor IX genes of four unrelated Chinese patients with hemophilia B have been identified by direct sequencing of amplified genomic DNA fragments. These four mutations occur in exon 8 of the factor IX gene. A C to T transition at nucleotide 30,863 changes codon 248 from Arg (CGA) to a new Stop codon (TGA), described in a previous family as factor IXMalmo3 (Green P M et al., EMBO J 1989; 8: 1067). A G to A transition at nucleotide 31,051 changes codon 310 from Trp (TGG) to a nonsense or Stop codon (TGA; factor IXChongquing2). A G to A transition at nucleotide 31,119 changes codon 333 which is for Arg (CGA) in normal factor IX, to one for Gln (CAA) in the variant previously described as factor IXLondon2 (Tsang T C et al., EMBO J 1988; 7: 3009) in a patient with moderately severe hemophilia B. The fourth patient has a novel C to A transversion at nucleotide 31,290, which corresponds to replacement of codon 390 which is for Ala (GCA) in normal factor IX, to one for Glu (GAA) in a patient with moderately severe hemophilia B (factor IXChongquing3). DNA sequences of amplified fragments from mothers of three showed both their son's variant and a normal nucleotide at the appropriate position, indicating that they are carriers. The fourth patient's (factor IXMalmo3) mother, whose DNA was not evaluable, was most probably a carrier because of her low plasma factor IX levels. PMID- 2270539 TI - Selenium dependent glutathione peroxidase: a physiological regulatory system for platelet function. AB - In human platelets the selenoenzyme glutathione peroxidase (GSH-Px) acts as a scavenger of the peroxides generated during the burst of arachidonic acid (AA) metabolism. Such a mechanism inhibits the biosynthesis of both thromboxane A2 (TXA2) and lipoxygenase products. The same mechanism is not effective on the prostacyclin (PGI2) biosynthesis from cultured endothelial cells. In order to evaluate this effect in vivo, besides in vitro, we activated the enzyme in eight normal volunteers by increasing their daily Se intake for 8 weeks, monitoring: platelet GSH-Px activity, platelet aggregation induced by AA and U 44069, and concurrent malondialdehyde (MDA) and thromboxane B2 (TXB2) production, urinary excretion of renal and systemic TXA2 and PGI2 metabolites, platelet enzyme activities of the hexose monophosphate pathway and glutathione content, platelet adenine nucleotides, bleeding time, plasma Se concentration. We found: a) progressive platelet GSH-Px activation by Se paralleling an enhancement of platelet aggregation threshold values for AA, but not for U 44069; b) concurrent inhibition of platelet biosynthesis of TXA2 both in vitro and in vivo while the biosynthesis of systemic prostacyclin was unaffected; c) a progressive increase in the bleeding time, unmodified by aspirin. In conclusion, we believe that Se dependent GSH-Px represents a physiological mechanism regulating the biosynthesis of prostanoids with implications in platelet function and that a Se dietary supplement might be considered in the prevention of arterial thrombosis. PMID- 2270540 TI - Identification of dense granule specific membrane proteins in bovine platelets that are absent in the Chediak-Higashi syndrome. AB - Platelets from cattle with the Chediak-Higashi syndrome (CHS) have a platelet dense granule deficiency. One hypothesis for the platelet dense granule deficiency is that the granule is simply not formed in CHS megakaryocytes (MK). Alternative hypotheses include that the granule is assembled in CHS MK but a functional amino-nucleotide-cation storage complex cannot be formed or that the dense granule or its precursor fuses with other granules. This study was undertaken to determine if membrane proteins specific for platelet dense granules can be identified in membranes of other granules in CHS platelets. Platelets were disrupted; a mixed-granule fraction and alpha-granule enriched, mitochondrial enriched, and dense granule-enriched subfractions were obtained. Membrane proteins in these intact granules were radiolabeled and the granule underwent hypotonic lysis. Membrane proteins were extracted from granule "ghosts", separated, and then visualized by autoradiography. Three major proteins were identified in platelet dense granule membrane subfractions. Two of these proteins could be identified in membrane extracts from the mixed-granule fraction from normal platelets. They could neither be identified in extracts from the mixed granule fraction of CHS platelets nor in membranes from alpha granule-enriched and mitochondrial-enriched subfractions. The absence of dense granule membrane proteins in membranes of other organelles within CHS platelets suggests that fusion of dense granules or its precursor with other granules cannot account for the platelet dense granule deficiency in CHS platelets. PMID- 2270541 TI - von Willebrand factor (vWF)--why are the largest multimers most efficient in hemostasis? PMID- 2270542 TI - Gangliosides of T lymphocytes: evidence for a role in T-cell activation. PMID- 2270543 TI - Microcytotoxicity assay using mouse L cells transfected with human MHC class II genes. A method and its application. AB - Modifications of the standard microcytotoxicity assay make it possible to use this technique to screen both alloantisera and monoclonal antibodies with mouse L cells transfected with Class II genes. It is necessary to maintain a protein-rich environment in order to prevent nonspecific complement lysis. Selection of the complement itself is also an important factor, the best results being achieved using a commercially available complement that had previously been absorbed with mouse cells and used at a dilution of 1/8. Using this modified method with transfectants of DW2 origin we could show that alloantisera against DRw15 recognize the DRB1*1501 gene product, whereas broad DR2 sera react only with the DRB5*0101 product. This technique can be applied successfully to study the fine specificity of polymorphic monoclonal antibodies, as shown by the reactivity of HU-30 which binds to the LDR2b transfectant and not to the LDR2a, indicating that the antibody recognizes an epitope present on the DRB1 chain and not the DRB5 chain of DR2 cell lines. PMID- 2270544 TI - [Investigations of the influence of Bacteroides gingivalis and Haemophilus actinomycetemcomitans in periodontitis]. PMID- 2270545 TI - [Effect of Cyclosporin-A on gingiva]. AB - Cyclosporin-A is a new immunosuppressive agent which has been used successfully to prevent organ rejection. Gingival overgrowth is one side-effect of the drug which is of interest for the dentist. The pathogenesis of the gingival alteration is unknown, but the dental plaque is discussed as a co-destructive factor. PMID- 2270546 TI - [Etiology of alveolitis and its therapy with indomethacin]. AB - The local antiphlogistic therapy of alveolitis was founded from the importance of inflammation in the etiology. Indomethacin (3% age oily solution) was analysed on their effectiveness. In the control group was treated with chlorphenol-camphor menthol-solution (ChKM) with addition of procain substance on the gauze strip. Indomethacin is significantly more active with regard to effectiveness, decrease of pain intensity and achievement of painlessness. The local therapy of alveolitis, is free of risk with solution out of Metindol--vials under dosage up to 6 milligram indomethacin substance. PMID- 2270547 TI - [Method of transplantation of upper retained canines]. AB - A holding device was introduced by mean teeth for transplantation can be fixed during all extraoral procedure. PMID- 2270548 TI - [Studies on juveniles' education for health of teeth and mouth. 2. Juveniles' knowledge of dental health and behavior]. AB - General recommendations about healthy way of life and dental health are well known to juveniles aged 12 to 16; but detailed information which completes and reinforces this general knowledge in a useful way is to a large extent lacking. Knowledge and behaviour of juveniles correlate with age, sex and success at school. An important role in developing a healthy way of life plays the family education. Point of contact for the dentist is the upgrading of dental screenings by a conform-intensive arrangement of these direct and very individual consultations. PMID- 2270549 TI - [Experiences with material and clinical properties of the Ni/Cr-alloy Gisadent NCS1 under consideration of the Silicoating-procedure]. AB - Investigations to the corrosive behavior in artificial saliva, to shear-bond strengths and to the formation of gaps in composite-alloy-compounds produced by using the SILICOATING-PROCEDURE show the better properties of the alloy GISADENT NCS1 respectively to NCA. The clinical results are in agreement with these facts, but it is necessary to pay attention to the small changes in the technological process. PMID- 2270550 TI - [Formation of circulating immune complexes in apical periodontitis]. AB - On the basis experiments on guinea pigs it is determined the quantity of circulating immune complexes in the blood in case of apical periodontitis. Over the whole experimental period it is stated an increase of these complexes in the blood. These results had us to assume a participation of immunologic reactions in the pathogenesis of the apical periodontitis. PMID- 2270551 TI - [Phagocytosis estimation in patients with post juvenile periodontitis by using isotope method]. AB - The report presents the phagocytosis estimation in patients with post-juvenile periodontitis applying the staphylococcus aureus bacteria marked with C14 isotope. The examination was carried out in 20 patients and 10 controls. Statistically significant decrease of phagocytosis was found in diseased patients. No difference was noticed in phagocytosis at various concentrations of serum. PMID- 2270552 TI - [Morphological features of regional lymph nodes and coagulation of the draining lymph in case of experimental apical periodontitis]. AB - During the early stages of experimental apical periodontitis the vascular permeability of the postcapillary venule is increasing. In the lymph draining from the submandibular lymph node it develops a syndrome of disseminated intravascular coagulation. In the sinus of the lymph nodes are stated fibrin sedimentation and thrombus formation. These processes are caused by a correlation of lymph and blood clotting factors and are not existing in the later inflammatory processes. PMID- 2270553 TI - [Treatment with Nance palatal arch of adult patient with onesided++ malocclusions of Class II]. AB - The problem of treatment oneside malocclusions of adult patients needs to concern of anchorange. To use palatal arch by Nance, iths an alternative way to extraoral pull. PMID- 2270554 TI - [Causes of refusal of care offered from the orthodontics]. PMID- 2270555 TI - [Root fracture--after a traumatic insult 16 years ago. Case report]. AB - It is presented the recovery of an intra-alveolar transverse fracture in the mean third of the root at 11, the right upper incisor, of a 36 years old patient clinically and radiologically. The tooth is still in full function after a traumatic insult 16 years ago. The immediate application of an acrylate splint covering the crowns is considered the best suited means of therapy. PMID- 2270556 TI - [Design and experiences in checking of a compressed air suction device for the oral surgery and comparison with conventional devices]. PMID- 2270557 TI - [Investigations of chemical corrosion of Ni/Cr-alloys]. AB - Dental final and auxiliary materials have to be biocompatible. Before using sumptuous biological testing methods corrosions studies allow to check up this property. Our investigations have been carried out by anodic polarization measurements. We tested traditional and further developed Ni/Cr-based alloys in independence to pH-value and composition of the electrolyte. The result is that the new with the help of an extensive experimental program developed Ni/Cr-based alloy Gisadent NCS 1 (Institute of Non-Precious Metals, Freiberg, GDR) shows a good corrosion resistance in comparison with other commercial products. PMID- 2270558 TI - [Effect of helium-neon-laser radiation on microbes]. AB - In a well-defined in-vitro experiment the effects of a He-Ne-laser of 6 mW output on some dominating microbes in the oral cavity were studied by using a scanning electron microscope. No changes on the surface in the irradiated colonies could be seen even after an exposition lasting for 60 minutes (continuous or pulsated wave). Therefore an antibacterial effect of softlaser-irradiation sometimes described in literature in questionable. PMID- 2270559 TI - [Experimental studies of the proper indication of inlay and crown therapy in lateral tooth areas]. AB - In the framework of a study involving both experimental and clinical tests, two preliminary tests were made to measure and compare the edge lengths of crowns and inlays and the substance losses after tangential and circular stage-type preparations. As revealed by the results, both the three-face and two-face cast fillings in the lateral tooth area have a longer restoration edge than corresponding cast crowns. The weight loss after crown preparations involving a circular stage is greater by one third than after a tangential preparation. In this context, ways of properly using restorative means of therapy in clinical dentistry are discussed. PMID- 2270560 TI - [Possibilities of root canal filling with gutta-percha. A critical investigation of different techniques]. AB - 92 root canal fillings were performed using single guttapercha point with sealer (chloropercha) and lateral condensation of gutta-percha. Neither with single point nor with lateral condensation methods it is possible to achieve advantages in clinical or radiographic success. Nevertheless, the lateral condensation of gutta-percha is a suitable method for beginners to learn the complicated technique of root canal obturation. PMID- 2270561 TI - [Cofferdam- system of VEB Medizinmechanik Suhl]. PMID- 2270562 TI - [Results valuation of adhesive bridges--3-year study]. AB - 139 of 169 adhesive-bridges, incorporated from 1984 bis 1987, were reexaminated in 1988. The failure rate was 37.5% with a mean functional period of 27.3 months. The patients were in average 40.5 years old. Rate of success is discribed depending on the localization and pillar-link-relation. The peaks of loss were after 300 and 900 days incorporation period. Conclusions for indication, prognosis and methodical references are given. PMID- 2270563 TI - [Clinical evaluation of the amalagam restorations for cavities Class I and Class II. 3: Comparison between dental school and dental institutions in the community]. AB - Comparison of conventional amalgam restorations produced either in dental college by students or in out-patient department showed that the portion of clinical acceptable restorations was higher at the college. The frequency of secondary caries was distinctively higher in the out-patient department (28.2%) than in the college (16.4%). Secondary caries mainly caused unacceptable quality of fillings of both the institutions. Causes brought about by material defect prevailed at the dental school. In the community errors of preparation mainly led to secondary caries. PMID- 2270564 TI - [Evaluation of the efficacy of sanguinarine using the experimental gingivitis model]. AB - Some studies showed positive results in testing the efficacy of sanguinarine delivered as oral rinse or dentifrice against plaque and gingivitis. The application of a gel containing 0.05 and 0.5% sanguinarine using special trays did not prevent plaque formation in regions with no oral hygiene. In contrast to placebo the 0.5% sanguinaria-gel was able to retard the formation of an experimental gingivitis. Chlorhexidine was superior to sanguinarine. Side effects were not detected. PMID- 2270565 TI - [New demands of dental early diagnostics problems and present approaches in the field of research methodology]. AB - For the purpose of prevention and early therapy it is necessary to replace empiricism by a diagnostics which can be reproduced, and by objective qualitative and quantitative findings. Traditional and new methods are to be used in combination. PMID- 2270566 TI - ["Implant"--software for the documentation of statement and course in the special dentist hour consultation of implantology]. AB - A programsystem is presented which supports the attending physician on entering symptoms of clinical and paraclinical parameters. The system runs on personal computer with Z-80 CPU under dBASE II. The program consists of six parts: 1. simple patient data, 2. oral documentation, 3. diagnostical base program, 4. sketch of therapeutics, 5. dispensaire documentation. It aims on the reduction on routine work (e. g. data in- and output) and simple statistical analysis (view of success of several implantationsystems). PMID- 2270567 TI - [Vademecum preventive stomatology. 1. Preventive alliance]. AB - The improvement of oral health conditions supports on partnership between social, personal and professional activities. The issue might be described by the term preventive alliance. PMID- 2270568 TI - [Application of fluoride varnish Duraphat with a cotton carrier respectively a syringe for cartridges--a comparison study]. AB - A study for comparing two methods of Duraphat application in children of the 1st and 6st grade was carried out to examine material allowed, expenditure of time, handling of the instruments and hygienic aspects. There was established, that application with syringe for cartridges and bended tubule was better than the application with cotton carrier, concerning both the duration of application and economical aspects of the material allowed. Therefor the use of syringe for cartridges for the application of Duraphat in collective and individual caries prevention is recommended. PMID- 2270569 TI - [Prevalence of damages of dental, the oral and the jaw areas among workers exposed to substances in a chemical company]. AB - 320 workers exposed to chemical in a large petrol-company and 100 nonexposed workers under the nearly same conditions of work and life were examined on damages of their dental, oral and jaw areas. As criterias of the examinations were used DMG/T-Index, Oral Hygiene-Index (Quigley/Hein, Greene/Vermillion) and the Parodontopathy-Index according to Kotzschke. The results of the examinations was a higher prevalence of damages of the periodontium among the workers in the chemical company in comparison to the control group. Within the several groups of workers exposed to chemicals were found significantly differences of the damages depending of exposures. PMID- 2270570 TI - [Care programme and barriers by apprentices]. AB - About 126 apprentices were questioned for their knowledge and habits regarding oral health to clarify motives and hindrances, to improve the dental care programme and to attain changes of their behaviour. Good expedient and methods for improving oral health of apprentices should be--in addition to regular check up--attractive lectures and discourses, instructed training of brushing, acceptance of the individuality of the apprentices, influence of fluoride application and measures and guidelines of feeding. PMID- 2270571 TI - [Evaluation of efficiency of dental care for children--results of a cross sectional study]. AB - Using special parameters like the percentage of treated children, degree of treatment and the rate of secondary caries, a retrospective estimation of dental care for children in Rostock County was performed. After that the best results in dental care could be recorded in children of towns. The degree of treatment generally was worse in children of a rural population. On the one hand there is demanded an equalizing of the disproportions in the personal situation in dentistry for children, on the other side there is recommended a yearly analysis of the efficiency of treatment and based on this a territorial program for dental care in children. PMID- 2270572 TI - [Hemisection--case report]. AB - The maintenance of teeth for a long time is a main goal of dentistry. Hemisections and root amputations are small surgical methods to conserve impaired teeth for periodontic, endodontic and prosthodontic view part. The successful hemisection of a lower jaw molar is demonstrated by a clinical example. PMID- 2270573 TI - [Adult periodontitis]. AB - The etiology and the pathogenesis, the diagnosis and the therapy of adult periodontitis (AP) are reviewed. Data from epidemiologic studies performed in recent years give a better knowledge of AP-progression. Successful long-term maintenance care give the proof that individual tooth preservation is life-long possible. PMID- 2270574 TI - [Construction and managing of maintenance care in periodontology]. AB - The maintenance care of periodontal treated patients is the necessary prerequisite for the individual long-life tooth preservation. The recall interval derives from the recidivity, the compliance of the patient, and from the individual disposition. The use of a self-developed data-bank-system relieve evaluation and processing of the extensive data which will be raised site specific in the recall session. It will be given some directions to the content of the periodontal maintenance care. PMID- 2270575 TI - [Chemical crystal aspects of remineralization of dental enamel]. AB - Incipient dental caries at the stage of demineralization is reversible, and remineralization can be achieved by the help of locally applied fluorides. In crystalchemical experiments, however by treating natural apatites with lanthanides Ce, La, Pr, Nd, Sm, Eu, Tb...Y, Sc, a more resistant complex could be developed. In this study extracted human molar teeth were kept for 60 days in Cerium (III)-nitrate solution, in order to investigate the incorporation of Ce3+ into human sound and carious enamel by light-microscopic-, and electronmicroprobe methods. Ce3+ was incorporated in sound enamel as well as into the incipient carious lesions, showing the histological characteristics of a remineralizing lesion. The mean values of the microprobe analysis data showed an increase in Ce3+ changing place with the Ca2+, the developing cerium-apatite being more hard an resistant from a mineralo-physical point of view. PMID- 2270576 TI - [Width of attached gingiva and periodontal condition in longitudinal observation in young female persons]. AB - I have investigated twice during a span of 2.5 years, the state of periodontium in female students of secondary schools in Szczecin. The second examination has revealed a narrowing of the attached gingiva in 50.5% of the subjects, without change in the state of periodontium, as represented by the Russell's index. PMID- 2270577 TI - [Progression and stagnation of periodontal disease]. AB - Local factors may contribute to acute exacerbations of the periodontal disease, however, their pathological basis is systemically established. The more bacteria and bacterial products get into the periodontal tissue the more serious is destruction. Host's resistance controls composition of the subepithelial bacterial flora. Under condition of defective phagocyte function bacteria, otherwise occurring rarely in the pocket, multiply quickly and penetrate the periodontal pocket epithelium. Specific immune defence can stop them only in the subepithelial conjunctive tissue causing its destruction. Juvenile periodontitis goes with defects of granulocyte function and an aggressive pocket flora. These patients need antibiotics taken systematically, removing of the infected pocket epithelium and regular recalls. Care of patients with adult periodontitis is limited to good oral hygiene. PMID- 2270578 TI - [Representative epidemiologic study of influence factors on the periodontal loss of attachment]. AB - The influence of age, inflammation intensity, tooth surface quality (caries, fillings), as well as mucogingival conditions on the loss of attachment was examined in 2000 probands. The loss of attachment was subdivided into periodontal pocket-formation and recessions. Determining cause is not the age but the inflammatory degree even if there is a significant increase of the attachment loss from age group to age group. The main part of the attachment loss increasing with advancing age is caused by recession development. Then, the individual dispersion is very high. Incorrect restorations, caries but also correct fillings increase periodontal disease. Mucogingival conditions show importance only in extreme case. There are less inflammations with pocket-formation than recessions. A preventive oriented basic care of the population is necessary to reduce irreversible damages of the periodontium. PMID- 2270579 TI - [Studies on the condition of marginal periodontium depending on the shape of the bridgework body]. AB - Within an 8-years-longitudinal study 40 patients with 30 tangential and 28 open bridges were examined. The accumulation of plaque as well as the degree of inflammation of the gingiva adjacent to the bridgework binder and the bridgework bodies were determined by means of selected indices, and the data obtained were compared to those evaluated when the bridges were fitted in. The results show that the accumulation of plaque (on) with open bridge was slightly elevated as compared to tangential bridges whereas the inflammation of the gingiva was significantly increased with tangentially shaped bridgework bodies. For this reason open bridges should be used further more in areas, where aesthetics play only a secondary role. PMID- 2270580 TI - [Contents of phosphate and calcium in whole-saliva of test persons with high and low caries prevalence]. AB - In a cross-sectional study the contents of phosphate and calcium in stimulated resting whole saliva of persons with high resp. low caries prevalence were examined. In the saliva of persons with a low cares experience significantly higher phosphate--and calcium--concentrations could be found. PMID- 2270581 TI - [Value and importance of treatment with OTC in selected patients with marginal periodontitis]. AB - Over a period of 14 days we have treated 27 after special criterious selected patients with 250 mg OTC three times/day. We compared these results with those of 25 patients--of a placebo-group. The analysis included clinical and microbiological parameters. It could be pointed out, that the OTC-therapy results in a significant improvement of the examined parameters stile 6 months after starting with the therapy. PMID- 2270582 TI - [Black's rules for cavity preparations--anachronism or adequate plumb line?]. AB - On the basic of a literature review Black's rules of cavity preparations are discussed. In the summary it suggested that the rules are valuable to discuss, but new perceptions had modified them. The contemporary cavity preparations saved the teeth structures and payed regard to the properties of filling materials. PMID- 2270583 TI - [Combined valuation of the success of therapy of orthodontic anomalies, periodontal diseases and dental caries]. AB - Using the DMF/T, GPM/T and CPITN-index systems, the numerical evaluation method according to Eismann and measuring the occlusal contact areas in static occlusion in 101 orthodontically treated adolescents and young adults the effect of complex preventive and therapeutic programs was studied. The used parameters allow to characterize oral health status. After completing the orthodontical treatment there is a need to continue preventive programmes and therapeutic interventions in adults to reach stable oral health conditions. PMID- 2270584 TI - [Clinical-epidemiological characteristic of periodontal conditions]. AB - Clinical-epidemiological screening procedures of periodontal conditions, which support on presence or absence of gingival bleeding or periodontal pockets, underestimate the severity of periodontal disease and do not reflect disease changes. The attachment level index might be a useful adjunctive tool for characterizing the pattern of severity as well as disease changes. PMID- 2270585 TI - [Frequency and localization of facets in adults with correct dental arches and malocclusion in anterior teeth region regarding periodontal reaction and occlusal guidance]. AB - We investigated 322 patients, 20 and 40 old to find connections between the occurrence and localisation of facets, malocclusion and dynamic occlusion and estimated special aspects of periodontal reactions. The symptoms "anterior crowding", "increased overbite and overjet" didn't effect an increasing of frequency of facets in comparison with eugnathic denture. We found, that the facets decreased in lateral segments if the overbite became deeper and on the other hand number of facets increased with advancing years. The localisation of facets and occlusal guidance of dynamic occlusion coincided only in one third of investigated cases. Balancing and hyperbalancing teeth showed frequent facets. There was a direct relationship between increasing frequency and intensity of gingival retraction and the level of the abrasion of the hard tooth substance. PMID- 2270586 TI - [Education of youth for tooth and oral health. 4. Aspects of behavior modification, family education, initiative, and responsibility]. AB - Behavioral modification is understood as a complex basic process of change. At the place of engraved (indifference or faulty) behavior comes conscious health behavior. Healthy way of life is a dynamic characteristic. Protection against diseases implies knowledge and will; self-interest initiative, own participation, discipline. Health consciousness must be linked with directly responsible action. Children nd juveniles acquire the ability for a life-fit independence in thinking and acting above all in the closed social environment of the family as the smallest unit with personality forming group public. This home education process requires harmonization with the everyday school life and the life outside school PMID- 2270587 TI - [Endodontic treatment needs--situation and development]. AB - The endodontal treatment need has been forming a clinical order of magnitude. Its decline will be realized by a preventive-orientated oral health care strategy. PMID- 2270588 TI - [Possibility for the improvement of dental diagnostics using endoscopy optics]. AB - Results of investigations with endoscopy optics for dental microdiagnostic are reported. Submicroscopical structures of 10 microns can be identificated on definated test objects. Investigations of extracted teeth using endoscopy optics show the advantages for the necessary microdiagnostic. PMID- 2270589 TI - [Direct capping of the artificial exposed pulp in teeth with deep caries]. AB - We carried out clinical and histological investigations on teeth with superficial and deep caries in which we made an artificial exposure of the pulp to check the reactivity of the endodont. After one year we observed using clinical and x-ray methods successful treatment in 93.4% of the teeth. Histologically the number of successful treatment was 100.0% in teeth with superficial caries and 80.0% in teeth with deep caries. PMID- 2270590 TI - [Evaluation of root canal filling in X-ray picture]. AB - It has been experimentally shown that the x-ray picture cannot represent, with sufficient accuracy, the completeness of a root canal filling. The problems concerned are discussed. PMID- 2270591 TI - [Surgical therapy of gingival recessions. Longitudinal study of the effectiveness of two surgical techniques]. AB - First indication and contraindication of surgical procedures are discussed. In comparison of two surgical methods for the treatment of gingival recessions the better effect is by the two-phase-surgery. There is a dependence on age- and tooth-groups. PMID- 2270592 TI - [Studies on the prevalence of gingiva recessions in juveniles at the age from 15 to 25 years in consideration of preventive care]. AB - Studies resulted a prevalence of gingiva recessions of 13.7% at the age group of 15-19 years and of 29.9% at the age group 20-25 years. In consideration of investigated clinical attendant symptoms a structure of required parameters for its development is discussed and emphasized the importance of dental care aspects is emphasized. PMID- 2270593 TI - [Caries prevalence in 6 to 14 years old children--results of the Rostock cross sectional study]. AB - The results of a cross-sectional study of caries prevalence in 22,112 children age 6 to 14 years in Rostock Country are classified as moderate to high according to WHO criterions. Territorial differences in the caries prevalence have a strong connection to the degree of realisation of preventive measures. Over a control period of 20 years the average caries experience in children showed only little changes, a general caries decline couldn't be watched. PMID- 2270594 TI - [Effect of comprehensive preventive measures in children of dentists]. AB - Preventive measures, continuously realized in children of dentists cause significantly lower values of Plaque index, Sulcus-bleeding-index, CPITN and caries in all groups of age in comparison to other groups. PMID- 2270595 TI - [Influence factors on progression and result of the treatment of periapical inflammation]. AB - The removal of the root canal infection was rendered more difficult with initially present communication of the root canal with the oral cavity, the involvement of relatively resistant microorganisms (enterococci, candida spec. and others) in the infection, and the extensive destructions of the periodontium. Some reduction of the chance of success could be established in case of extensive lesions of the marginal, lateral and apical periodontium after a control period of three years. This indicates the role of the relations between periodontium and endodontium for the result of the therapy of periapical inflammations. PMID- 2270596 TI - [Electrochemical examinations to the influence of mechanical treatment of surfaces on the corrosion on different dental amalgams. 2: Measurements of potentiodynamic polarization with high polarization rate]. AB - In a cell with artificial saliva the electrochemical behaviour of amalgam specimens of Germadent, Duragam and ANA 2000 are characterized in dependence of different mechanical treatments of surfaces using cycling voltimetry. In the beginning the influence of roughness on the corrosion is evident, but increasing the influence of chemical composition dominant. Duragam-amalgam is most resistant to corrosion. The content of copper in Duragam has a better effect than the high content of copper in ANA 2000. PMID- 2270597 TI - [Prevention of the complicated eruption of the lower third molars and of all complications connected with it]. AB - A clinical x-ray examination of teenagers in the age of 16-18 had been done in this submitted work as well as the clinical process of the complicated eruption of the lower third molars and all the complications connected with it were analysed at the same time. Therapeutic-prophylactical measures were worked out with the help of examinations which were carried out. PMID- 2270598 TI - [Application of bupivacaine in ambulatory jaw surgery]. PMID- 2270599 TI - [Influence of functional therapy on the gingival recession in patients with wedge shaped defects. A 2.5-year longitudinal study of the etiology of periodontal atrophy]. AB - In 20 patients a free way space of greater than or equal to 1.0 mm and a cuspid protected guidance was formed. A previous study has shown, that prematurity and defective contacts reduce the free way space step by step and induce an artificial clenching. The front teeth was relieved in intercuspal position. The increase sof gingival recessions at the upper jaw was over five times significant slighter in treated patients than one in the 22 men of the control group. There was no significant, differences in the lower jaw. The recessions are represented as a sequence of a chronic biomechanical overloading. PMID- 2270600 TI - [Elucidation and control of parafunctions by means of a modified self-observation test by Schulte and their effective treatment by occlusal adjustment and reconstruction]. AB - A modified selfobservation test by Schulte enable us to differ parafunction quantitative as qualitative. By means of it were stated, toothclenching is induced by a missing or insufficient free way space on a large scale. Clenching could be reduced by occlusal adjustment and reconstruction significant about 45 percent. The free way space ought to be greater than or equal to 1 mm. The test is suitable for controlled treatment of temporomandibular joint and myofascial disorders. It could substitute electromyograms in outpatients, Toothclenching dominate with 85 percent before grinding with 27 percent in patients with wedge shaped defects. PMID- 2270601 TI - [Therapy of Class V cavities]. AB - Despite of the necessity of an increasing primary prevention the therapy of class V cavities will be of greater importance already in the next future. In this review of the literature the indications, advantages, disadvantages as well as the practical procedure for the therapy of cervical lesions with amalgam, metal inlays, composites, glass ionomer cements, porcelain restorations,a nd composite inlays are discussed. PMID- 2270602 TI - [Studies on the oral health status of elderly and old people in a rural district]. AB - There is reported on an epidemiological study to estimate the gerostomatological treatment need by examining in a rural district all people older than 55 years. The studies were carried out in compliance with the WHO-Basic Methods for oral health services. The results demonstrate that the oral health status of the old people is determined by loss of teeth and its functional consequences. Caries, diseases of the oral mucosa and TMJ-disorders are unimportant in the epidemiological point of view. The condition of porsthetic treatment is quantitative satisfactory in the age-groups up to 75 years. PMID- 2270603 TI - [Effectivity of ultrasonics by the root canal instrumentation]. AB - The investigative results showed that preparation of root canals is more effective with ultrasonic as compared to hand instrumentation. Areas like diverticula, canal enlargements or side canals were seen to be extremely clean. This is probably due to the effect of cavitation, implosion of small bubbles, the acceleration of minute particles and the formation of ultra sonic waves. The REM investigation showed no residual bacteria. The hand instrumented canals showed pulp remainders in the canal. PMID- 2270604 TI - [Indications for restorative treatment with posterior composite resins]. AB - The authors discuss the advantages and disadvantages of the restorative treatment with posterior composite resins. They warn against the uncritical application of such materials and formulate directions for their use. PMID- 2270605 TI - [Economic aspects of alveolitis]. AB - In 1680 cases of alveolitis ("dry socket") the national economic-loss is more than 339,693.-marks. Nearly 3 million teeth will be extracted in one year in the DDR. By a valuation of nearly 3% of the alveolitis 90,000 patients have this complication. That will be a economic-loss of 18.1 million marks in one year. The prophylaxis of this complication is therefore a most important problem. PMID- 2270606 TI - [Bilateral parotid gland aplasia--significance for oral cavity. Case report]. AB - Seldom case of bilateral parotid gland aplasia. Lead symptomatology exists in dryness of mouth and sequels. PMID- 2270607 TI - [About the availability of computers in the general stomatologic practice]. AB - A software-packet for the medical documentation in the general stomatologic practice is represented. The programme allows among others the print of findings, the therapeutic plan, the documentation of progress, the x-ray demand as well as the performance-proof. By that way the course of consultations, the mass examinations and the valuation is effective possible after a short phase of adaption. PMID- 2270608 TI - [Dentist-patient communication]. AB - Consulting patients about their expectations in their dentist and observing dentist-patient-communication in office-hours of 10 dentists necessity and reality are opposed. Problems are shortness of information and instruction of the patient, use of special vocabulary, inadequate reaction to patient's anxiety and insufficient mediation of salubrious references by the doctor. PMID- 2270609 TI - [Basic and advanced training in radiation protection in stomatology]. AB - Considering the importance of radiation protection in dental radiology and the respective legal regulations of the GDR, objectives and contents of basic and advanced training of responsible co-workers in radiation protection are described. Particular organisational aspects regarding training courses in the National Board for Atomic Safety and Radiation Protection are outlined. PMID- 2270610 TI - [Renewed examination of the group classification of partially edentulous arches by Eichner and application advices for studies on morbidity statistics]. AB - The groups A1 to C3 of the "group classification of partially edentulous arches" by Eichner are characterized by the number of teeth and the topography of the natural dentition. This could be demonstrated in a clinical study on 1000 patients prepared by Blume-Greger. The result shows a percentage of 49.5 in the groups A, 22.4% in the B-groups and 28.1% in the C-groups. Furthermore, these groups represent the course of tooth loss also regarding the functional value of the natural dentition. Thus, this classification provides a standard for the degree of morbidity of the dentition and is suitable for application in studies on morbidity statistics. When used for documentation files there is an error possibility of 1.9%. PMID- 2270611 TI - [In vitro evaluation of two composite material for posterior restorations]. AB - In this in vitro study the wear resistance and abrasiveness against opposing enamel cusps, marginal adaptation and radiopacity of two experimental composite resin materials were tested. The results indicated that in particular the fine particles hybrid showed low wear. The radiopacity of both materials tested was just acceptable. Marginal adaptation was insufficient in both cases, the reason being most probably the low viscous bonding agent and the polymerization shrinkage. Therefore both test materials are not suitable for use as direct posterior composite fillings. PMID- 2270612 TI - [Measurements of the mercury vapour concentration of the room air during dosing and trituration of amalgam by DMG 410]. AB - The testet mechanical amalgamators DMG 410 (VEB Dentalfabrik Treffurt) showed sufficient tightness. After dosing and trituration of 5 (during 30 min) and of 25 amalgam mixtures (during 2 hours) an increase of the mercury vapour concentration was measured from 0.003 mg Hg/m3 air of the room (blank value) to 0.008 mg Hg/m3 air of the room and to 0.018 mg Hg/m3 air of the room in an unventilated room. A significant decrease of the mercury vapour concentration could be established within 10 minutes by ventilation of the measurement room. PMID- 2270613 TI - [Investigations of sensitivity and reliability from Plaque-Index methods]. AB - Three independent examiners evaluated the oral and vestibular plaque-index-rate on all teeth at 100 probands. A 7-grade-index computer-transformed into the plaque-values by Quigley and Hein, Silness and Loe and the debris component of Oral-Hygiene-Index was used. From these tested index-methods the index by Quigley and Hein proved to be the better as to sensibility and reliability in comparison to the other two methods. PMID- 2270614 TI - [Vertical movement of teeth following preparation for inlays with preservation of cavity walls]. AB - By means of an indirect measuring procedure applied to 24 teeth including molars and premolars the extent of the teeth's vertical motion has been established. During the first three days after the neutralisation of the antagonistic contacts upon cavity preparation the scale and speed of the axial movement of the teeth were found to be larger than on the following four days (0.102 greater than 0.059 mm). It is recommended to apply cast fillings with a replacement of the occlusive area as quickly after the wax mould as possible because of the diminished gap due to the motion of the teeth. PMID- 2270615 TI - [Ways of tooth conservation by surgical techniques]. AB - Based upon innovations in the past 20 years regarding material--as well as surgical techniques indications are given for surgical conservation of teeth, in addition questions of current interest referring to root fillings are answered. Possible ways of tooth conservation by periodontal operations are shown. To conserve traumatically injured teeth guides for emergency treatment are given. PMID- 2270616 TI - [Stomatological identification after air disasters]. AB - The paper describes experiences of stomatological identification after two air disasters and shows potentialities and limits of an odontologic(al) comparison. The application of a 16-bit-computer is pointed out as the essential improvement of the work. PMID- 2270617 TI - [Oral health behavior and state and the effect and necessity of dental care in young and medium adults (Dresden prevention study)]. AB - In a baseline examination of a preventive study 319 randomly recruited patients of a dental school aged between 16 and 35 years were inquired about oral health behavior and the oral health state was determined clinically. The spectrum of methods included extended anamnesis, plaque index according to Silness/Loe, DMF/T and GPM/T-index. The health behaviour and the derived preventive and curative care needs show that the majority of patients need individual oral hygiene and nutrition advising, professional oral hygiene measures, fluoride application, as well as filling therapy. Early therapy of periodontitis is of importance. PMID- 2270618 TI - [Composition of rat serum proteins under the effect of acetaldehyde and ethanol]. AB - Concentration and composition of rat serum proteins have been studied both under the isolated acetaldehyde effect and against a background of the action of acute and chronic intoxication by ethanol. Acetaldehyde evoked an increase in the concentration of the total serum proteins, the value of this parameter remaining unchanged under the ethanol effect. A comparison of ethanol and acetaldehyde effects gives ground to suppose that the quantitative redistribution of blood serum proteins which observed under ethanol intoxication is to a considerable extent a result of the acetaldehyde effect and is determined by aggregation of proteins. PMID- 2270619 TI - [Comparison of the content of cholesterol, lipoproteins and serum proteins in rats, guinea pigs and rats for a atherosclerosis model]. AB - The hypercholesteremia parameters under similar experimental conditions against a background of the close initial level of cholesterol were considerably more expressed in rabbits than in guinea pigs. Rabbits showed clear symptoms of experimental atherosclerosis which were absent in guinea pigs. A comparative study of quantitative and composition variations in total proteins of the serum and fraction obtained by acid extraction indicated that the differences in dynamics and degree of cholesterinosis were expressed by features of the serum protein spectrum variation in the investigated kinds of animals. Especially close relation has been observed for the fraction components of acid-extracted proteins. The obtained results permit supposing that some kinds of animals have mechanisms connected with the function of the serum alkaline proteins preventing the development of hypercholesteremia and experimental atherosclerosis. PMID- 2270620 TI - [Interaction of N-phenyl-1-amino-8-sulfonaphthalene (ANS) with albumin in blood in hyperbilirubinemia]. AB - The fluorescent intensity of the N-phenyl-1-amino-8-sulfonaphthalene (ANS) probe significantly decreases in hyperbilirubinemic serum. A decrease of the albumin concentration and absorption of ANS fluorescence by bilirubin cannot explain such a considerable reduction of the probe fluorescence intensity. Measurements of the fluorescence decay kinetics has shown two types of sites occupied by ANS in albumin. ANS quantum yields in hyperbilirubinemic and normal serum are practically identical. The coupling parameters for ANS decrease, but the coupling constant increases under hyperbilirubinemia. As a result the coupling of organic anions with serum albumin significantly decreases if there is high anion concentration, and it does not decrease at low anion concentration. Bilirubin is not a main cause of a decrease of the albumin binding capacity. PMID- 2270621 TI - [Hydrophobic interaction of alpha-chymotrypsin with low molecular weight compounds]. AB - Data on alpha-chymotrypsin interactions with hydrophobic low-molecular compounds have been generalized. Existence of two sites of noncovalent interaction with hydrophobic nuclei of a ligand molecule is shown. When the substance to be bound contains only one hydrophobic nucleus, the interaction is mediated by a "hydrophobic pocket" of the enzyme--a binding site of amino acid residues which are, in the P1-position relative to the cleaved bond. Under these conditions substances with an asymmetric hydrophobic nucleus (of the tryptophan type) are better ligands for binding. In case of compounds containing several hydrophobic groups scattered in the space, interaction with the enzyme proceeds in two binding sites. New data are presented on the ligand specificity for binding sites of chymotrypsin in lower vertebrates. Relative position of hydrophobic groups of the ligand is shown as that of great importance for interaction with the enzyme. It is concluded that the binding sites of trypsin- and chymotrypsin-like proteinases of the lower vertebrates differ but less from each other as compared to binding sites of trypsin and chymotrypsin in mammals. PMID- 2270622 TI - [The effect of the delta-sleep peptide on the adrenaline level in rat tissues under normal conditions and during cold stress]. AB - Adrenalin content in the brain, liver and adrenal glands under the effect of cold stress grows by 314, 500 and 56% as compared to the control. A single administration of the delta-sleep inducing peptide (DSIP) in a dose of 12 microgram/100 g to intact animals makes the adrenalin content in the brain higher 1, 3, 6 and 24h after administration; two and three days later the adrenalin content in the brain does not change. The amount of adrenalin in the liver of the same animals increases 1, 3, 6 h and 1, 2, 3 days after DSIP administration. Intraperitoneal administration of DSIP induces an increase of the adrenalin level in the adrenal glands of rats an hour and a day after administration. Two days later the level of adrenaline decreases by 41%; 3, 6 h and 3 days after DSIP administration the content of adrenaline remains unchanged. As a result of the DSIP administration in a dose of 12 micrograms/100 g to the animals in the state of cold stress, the content of adrenalin increases in the rat brain by 129, in the liver--by 300, adrenal glands--by 44% as compared with the control. PMID- 2270623 TI - [Inactivation of yeast apopyruvate decarboxylase by lipophilic n-alkyl substituted thiazole salts]. AB - Yeast apopyruvate decarboxylase is irreversibly inactivated by 3-dodecyl-4 methylthiazolium bromide (I), 3-dodecyl-4-methyl-5-beta-hydroxyethylthiazolium bromide (II), 3-hexadecyl-4-methyltiazolium bromide (III), 3-hexadecyl-4-methyl-5 beta-hydroxyethyliazolium bromide (IV). 3-Octyl-4-methylthiazolium bromide (V) possesses insignificant inactivating properties. The relationship between residual enzymatic activity and concentration of thiazolium salts (II, IV) which are more similar structural analogs of thiamine is of the S-like pattern. In the case of thiazolium salts (I, III) this relationship is almost linear. The measure of inactivation of apopyruvate decarboxylase in the presence of substances (I-IV) increases with the hydrocarbon chain length of n-alkyl substituent of the quaternary nitrogen atom of the thiazolium salt. The calculated second-order-rate constants are 5.43.10(2) (I) 1.52.10(3) (II). 2.83.10(4) (III). 4.85.10(4) M-1 min-1 (IV). The UV spectroscopic method has shown that a hypsochromic shift of longwave absorbtion maxima and a decrease of their extinction occur under interaction of thiazolium salts (I-V) with tryptophan. This fact evidence for possible complexing of compounds (I-V) with indole residues of protein. The hydrophobic interactions are supposed to be a crucial factor in the inactivation mechanism of yeast apopyruvate decarboxylase. PMID- 2270624 TI - [The effect of phosphorylation on oxidative and CoA- and NAD+-independent turnover of pyruvate by pyruvate dehydrogenase complex in the brain]. AB - It was shown that in the presence of ATP and Mg2+ the phosphorylation of the partially purified pyruvate dehydrogenase complex and the enzyme in isolated brain mitochondria inhibited the oxidative activity of the pyruvate dehydrogenase complex. The phosphorylation did no affect essentially the nonoxidative decarboxylation of pyruvate to form CO2 and acetaldehyde. In native mitochondria from the bovine brain the nonoxidative activity of the pyruvate dehydrogenase complex reached about 10% as compared to the oxidative activity of enzyme. PMID- 2270625 TI - [Catabolism of labelled alpha-ketoglutarate, succinate, aspartate and gamma aminobutyric acid in nerve tissue; the effect of pyridoxal-5'-phosphate in vitro]. AB - Proceeding from estimation of the 14CO2 release from [5-14C]alpha-ketoglutarate, [1-14C] gamma-aminobutyric acid (GABA), [1,4-14C] succinate and [4-14C] aspartate (0.4-1 mM) during their incubation with homogenates of different brain areas with regard for the label position and stereospecificity of decarboxylation of citrate formed due to the metabolism, the relative intensity of their catabolism is determined: [1,4-14C] succinate much greater than [4-14C]aspartate greater than [5-14C] alpha-ketoglutarate much greater than [1-14C]GABA. The label release with catabolism of [1-14C] alpha-ketoglutarate considerably exceeds the intensity of decarboxylation of the above enumerated substrates. In all cases the maximum release of 14CO2 has been registered in the cortex homogenates, the minimum--in the medulla homogenates, and only under long-term incubation with high concentration of GABA (50 mM) maximum catabolism was registered in the medulla. Preincubation of nervous tissue with pyridoxal-5'-phosphate (40 microM) results in significant acceleration of catabolism of [1-14C] alpha-ketoglutarate, [5-14C] alpha-ketoglutarate and [4-14C] aspartate with an inconsiderable increase of catabolism of the rest of labelled substrates. PMID- 2270626 TI - [The role of ketone bodies in energy supply in cold-blooded animals during winter starvation]. AB - Natural winter starvation has been studied for its effect on the content of ketone bodies, oxaloacetate, glucose, 3-oxybutyrate-dehydrogenase activity level in the carp fry tissue. A compensatory mechanism of the energy supply in peripheral tissues is found proceeding by formation of ketone bodies in the liver and their distribution in the tissues of white muscles and brain. For the latter the ketone bodies in wintering serve as an additional oxidation substrate. PMID- 2270627 TI - [Characteristics of lipid composition and properties of the synaptic membranes of the cerebral cortex of rats of various ages]. AB - The content of cholesterol, total and individual phospholipids, fatty acid composition, level of lipid peroxidation, as well as viscosity of lipid phase of synaptic membranes isolated from the cerebral cortex were estimated in experiments on adult and old male rats. The content of cholesterol and cholesterol phospholipids ratio were found to increase with age. The total content of phospholipids remained unchanged during ageing, while their composition varied. An increase in the content of minor forms of phospholipids, i.e. phosphatidylserine and phosphatidylinositol, in the sphingomyelin/phosphatidyl ethanolamine ratio and, especially, in the content of lysophosphatidylcholine was found in old vs adult rats. No age-related changes were found in the viscosity of the lipid phase of synaptic membranes with purene used as a fluorescent probe. PMID- 2270628 TI - [The effect of synthetic protein fragments on humoral immune response]. AB - Effect of some protein and immunopeptide synthetic fragments on the humoral immune response has been studied. Some investigated peptides are shown to influence the antibody genesis at the secondary immune response to T-dependent antigen (bovine serum albumin) in mice. The serum antibody level specific for the bovine serum albumin is measured by enzyme-linked immunosorbent assays (ELISA). Possible mechanisms of the influence of such peptide fragments on the immune system is discussed. PMID- 2270629 TI - [Activation of "silent" antibodies and their interaction with antigens]. AB - Animal and human blood serum contains great amount of blocked (or "silent") immunoglobulins which, being activated by heating to 60 degrees C, pH decrease to 2.0-2.5 or treatment with 5M KSCN acquire a capacity to interact with different antigens. This interaction may be equally prevented or weakened by both identical and serologically non-related antigen, i.e. activated immunoglobulins are polyspecific. Polyspecific immunoglobulins show less affinity in comparison with monospecific antibodies, their interaction with antigens depends considerably on temperature. PMID- 2270630 TI - [Isoelectric heterogeneity and oxygen affinity of chicken hemoglobin, depending on age]. AB - Differences in the isoelectric spectra and in the molecular oxygen affinity to hemoglobin have been shown in 14-, 28- and 49-day hens. A regular decrease in the number of isoelectric components as well as a deterioration of the hemoglobin affinity to oxygen in 49-day hens have been observed. PMID- 2270631 TI - [Single- and double-stranded DNA from mouse liver after exposure to carbon tetrachloride]. PMID- 2270632 TI - [Lipoproteins of rat small intestine epithelial cells in D-hypovitaminosis]. AB - Chemical composition of lipoproteins has been studied in intestinal epitheliocytes of rats in normalcy and under D-hypovitaminosis. It is found that D-hypovitaminosis induces changes in the lipid and protein composition of lipoproteins. It is supposed that disturbances in biosynthesis of the lipoprotein components and their transport may be possible reasons of such changes. PMID- 2270633 TI - [Inhibition of glucose in Zajdela hepatoma by 6-phosphogluconate; the role of 3 phosphoglycerate]. AB - Influence of 6-phosphogluconate and 3-phosphoglycerate have been studied for their effect on the fructose-6-phosphate glycolytic transformation reactions in homogenates of the Zajdela hepatoma cells. It is established that 6 phosphogluconate inhibits formation of lactate from fructose-6-phosphate and increases the ratio: dioxyacetone-phosphate/lactate. The influence of 6 phosphogluconate on the formation of lactate from the fructose-1,6-bisphosphate is similar. 3-phosphoglycerate removes the effect of 6-phosphogluconate, its content being unchanged in samples, which indicates rather the regulatory, than the substrate role of 3-phosphoglycerate. Analogous experiments with homogenates of the rat liver show that 6-phosphogluconate inhibits hexosephosphate isomerase, but almost all the introduced substrate (fructose-6-phosphate) is transformed into glucose. Processes of fructose-6-phosphate consumption in the hepatoma and liver are opposite. PMID- 2270634 TI - The downward spiral of cattle veterinary practice. AB - Farm work for the cattle veterinary practitioner has declined in recent years, and further decline seems inevitable. With fewer dairy farms, and cattle farmers calling upon the veterinary surgeon less frequently, mixed practices are able to compensate by spending ever more time on small animal and horse work. But as cattle farmers know full well that younger veterinary surgeons are getting ever less experience with cattle, they are even less inclined to consult them. Here, I review the reasons for the downward spiral, and look for some solutions. PMID- 2270635 TI - An outbreak of the equine rhabdomyolysis syndrome in a racing yard. AB - An outbreak of muscle stiffness and poor performance among 59 thoroughbreds at a Newmarket flat racing yard was investigated between the beginning of May and the end of June 1986. Over a third of the horses showed signs of muscular stiffness, and 38 had, at one or more of the sampling times, creatine kinase (CK) activities above 200 iu/litre and, or, aspartate aminotransferase (AST) activities above 300 iu/litre when they were sampled six to eight hours after exercise. The following season, at a similar time and stage of training, only four of 39 horses sampled had CK activities between 200 and 300 iu/litre, and three had AST activities between 500 and 600 iu/litre. Plasma samples from 18 animals sampled at the start of the investigation and 13 days later were tested for the presence of antibodies to equine herpesvirus (EHV). Ten of them showed a response highly suggestive of an EHV-1 infection. No significant abnormality was found in the fractional electrolyte values from seven randomly selected animals. Unusually high numbers of normally sized and stained fibres with centrally placed nuclei as well as groups of small muscle fibres were found in muscle biopsies taken from three animals which continued to have high enzyme activities and show recurrent signs of muscle stiffness. PMID- 2270637 TI - Caseous lymphadenitis in goats in England. PMID- 2270636 TI - Use of scanning electron microscopy to investigate dental calculus in dogs. AB - The formation of dental calculus in dogs is a major problem. Scanning electron microscopy of tartar specimens from dogs revealed on the outer surface of the plaque polymorphic configurations, more or less arranged as free filaments, corn cobs or swab-like structures. Uninhabited bacterial recesses were found on the inner surface of the calculus. Calcification may occur between or within the bacteria. Elucidating the mechanisms of calculus formation should help in the development of prophylactic measures. PMID- 2270638 TI - Rinderpest in crossbred calves weaned at birth. PMID- 2270639 TI - Feline sporotrichosis: an increasingly important zoonotic disease in Malaysia. PMID- 2270640 TI - Meat hygiene. PMID- 2270641 TI - Ante mortem inspection at UK slaughterhouses. PMID- 2270642 TI - Colostral supplements and substitutes. PMID- 2270643 TI - Design of water bath stunners in broiler plants. PMID- 2270644 TI - Premature placental expulsion. PMID- 2270645 TI - Spongiform encephalopathy in pigs. PMID- 2270647 TI - Homologies between the major histocompatibility complex of man and cattle: consequences for disease resistance and susceptibility. AB - The major histocompatibility complex (MHC) of mammals contains a large number of mostly duplicated genes. In the HLA system (the MHC of man), which is by far the best-studied major histocompatibility system so far, roughly 20 genes have been defined and mapped. They code for three classes of proteins: HLA-A, -B and -C (Class I), HLA-DP, -DQ and -DR (Class II) and serum complement components C2, C4 and Bf (Class III). Furthermore, the region contains genes for 21-hydroxylase (21 OH) and tumor necrosis factor (TNF). The MHC thus forms a chromosomal segment containing several clusters of genes of only partially defined biological significance, but ondoubtedly playing a role in disease susceptibility. In view of the recently obtained structural information on BoLA, the MHC of cattle, it is hypothesized that susceptibility to diseases in cattle is associated with BoLA in the same way as human diseases. Finally, new technical and conceptual developments in the field of MHC research and their application to the BoLA system are discussed. PMID- 2270646 TI - Evidence for prolactin as the main luteotrophic factor in the cyclic dog. AB - The role of prolactin and LH in the control of the function of the corpus luteum in the dog was studied. Experiments were performed to interfere with the secretion of a) prolactin by administering a dopamine agonist and b) LH by desensitisation with a long-acting LHRH and by stimulation. Treatments with prolactin-lowering dosages of bromocriptine, (20 micrograms/kg body weight twice a day, orally; n = 8) which started between day 1-5 (n = 4) and day 20-24 (n = 4) of the luteal period resulted in a similar pattern of progesterone, concentration in peripheral blood in both groups. The progesterone release in the second half of the luteal period (13.1 +/- 1.8% (sem) of the progesterone release of the total luteal period) was significantly lower than in control dogs (24.7 +/- 2.2%). Treatment at about day 30 of the luteal period with LHRH CR (1.34 mg, intramuscularly; n = 3), which significantly suppressed the LH level, did not reduce the progesterone release in the second half of the luteal period, 21.3 +/- 4.7% compared to 24.7 +/- 2.2% in the control dogs. The endogenous LH peak resulting from treatment with LHRH had no effect on the progesterone concentration in the blood. It is concluded that prolactin is the main luteotrophic factor in the cyclic dog during the second half of the luteal period. PMID- 2270648 TI - In vitro activity of flumequine in comparison with several other antimicrobial agents against five pathogens isolated in calves in The Netherlands. AB - The in vitro activity of flumequine in comparison with several other drugs was tested against 17 P. multocida, 16 P. haemolytica, 21 S. dublin, 21 S. typhimurium and 21 E. coli strains, isolated in (veal) calves in the Netherlands. The MIC50 of flumequine for the respective pasteurellas was 0.25 and 1 microgram/ml, for the salmonellas and E. coli 0.5 micrograms/ml. In comparison with flumequine, enrofloxacin and ciprofloxacin showed higher in vitro activity, with MIC50 less than or equal to 0.008 micrograms/ml for ciprofloxacin. Decreased susceptibility of the pasteurellas was found for kanamycin, neomycin, streptomycin, gentamicin, oxytetracycline and doxycycline. The MIC50 of minocycline for P. multocida was 0.5 micrograms/ml and there was no cross resistance with the other tetracyclines. P. multocida was very susceptible to ampicillin (MIC50 less than or equal to 0.03 micrograms/ml), P. haemolytica, however, was 100% resistant to this drug. Both pasteurellas were susceptible to cephalothin and approximately 50% of the strains of both bacteria were resistant to chloramphenicol. The MIC50 of either spiramycin or tylosin was greater than or equal to their respective breakpoint-MIC values. Both pasteurellas were susceptible to the combination of trimethoprim and sulphamethoxazole. However, for P. multocida, the addition of sulphamethoxazole to trimethoprim had no synergistic effect on its MIC. In comparison with trimethorpim, aditoprim was less potent. Therefore only P. multocida was susceptible to aditoprim. PMID- 2270649 TI - Aluminium intoxication in a dog. AB - A two-year-old male Barsoi dog was presented after a two-week period of muscle twitching and convulsions during exercise, which worsened to a state of tetraparesis and coma. Removal of a gastric foreign body, containing aluminium, resolved the presenting signs. Parallel with this clinical recovery the elevated serum levels of aluminium decreased to values of two normal control dogs, suggesting that the neurological signs were due to A1 intoxication. PMID- 2270650 TI - The efficacy of netobimin against a benzimidazole susceptible and a resistant strain of Haemonchus contortus in sheep in The Netherlands. AB - Netobimin was tested for efficacy against Haemonchus contortus using 7 groups of 5 parasite-free lambs of six months age. The lambs in group 1 and 2 were infected with 10,000 larvae of a benzimidazole susceptible strain and those in groups 3-7 with the same dose of a resistant strain. The following treatment scheme was applied 21 days after infection: lambs in groups 2 and 4-7.5 mg kg-1 netobimin, in group 5-20 mg kg-1 netobimin, in group 6-5 mg kg-1 oxfendazole and in group 7- 3.8 mg kg-1 albendazole. The lambs in groups 1 and 3 remained untreated. All lambs were slaughtered 28 days after infection. Egg counts decreased in all lambs after treatment, but increased again in lambs in groups 4, 6 and 7. There was a slight increase in lambs in group 5, while those in group 2 remained negative. Post-mortem worm counts showed a reduction of 99.8 per cent in lambs in group 2 compared to those in group 1. In lambs in group 4-7 the reduction of worm counts was respectively 40.9, 89.5, 24.7 and 40.7 per cent compared to those in group 3. Egg development assays carried out 20 days after infection showed an average LD50 of 0.46 mg ml-1 thiabendazole for the resistant strain. After treatment (day 27) the LD50 was 0.53, 0.48, 0.58, 0.56 and 0.47 in lambs in the groups 3-7. It is concluded that netobimin and other (pro)-benzimidazoles should not be used in cases of benzimidazole resistance and that levamisole, pyrantel tartrate or ivermectin are preferable. PMID- 2270651 TI - Gas chromatographic-mass spectrometric confirmation of 19-nortestosterone in the urine of untreated boars--effect of the administration of Laurabolin. AB - The presence of 17 beta-19-nortestosterone (nandrolone, NT, 17 beta-19-NT) and its epimer 17 alpha-19-nortestosterone (epiNT, 17 alpha-19-NT) was investigated in the urine of six untreated boars, obtained from experimental farms. The presence of 17 beta-19-nortestosterone was screened by RIA and HPTLC and confirmed by GC-MS analysis. Additionally, the two epimers (NT and epiNT) were investigated in the urine of a boar (two-year-old miniature male pig weighing 50 kg) before and after injection of 100 mg Laurabolin (nortestosterone laurate, Intervet N.V., Belgium). The isolation of the steroids was based on sample clean up with solid phase extraction and subsequent high-performance liquid chromatography. Both gas chromatographic retention data and mass spectrometric data (selected ion monitoring and full spectrum) were used for detection and identification. The presence of 17 beta-19-nortestosterone in the urine of the boars that were not injected proves the endogenous production of the steroid. The absence of the 17 alpha-epimer in the urine of the injected boar suggests that 17 alpha-19-nortestosterone is not a major metabolite of 17 beta-19-nortestosterone. PMID- 2270652 TI - The influence of the injection site on the bioavailability of ampicillin and amoxycillin in beagles. PMID- 2270653 TI - [Roentgeno-morphologic characteristics of the principal forms of pulmonary sequestration]. AB - Basing on roentgeno-morphological correlations, three morphological types of pulmonary sequestration (PS) were singled out: intrapulmonary, intrapleural (peripulmonary) and extrapleural (mediastinal). PS signs on a skiagram can be of two types: spherical and cavitary. Reliable clinicoroentgenological diagnosis of PS is hardly possible and of hypothetical nature. Transthoracic puncture is the most effective and common diagnostic method. PMID- 2270654 TI - [Differential diagnosis of an accumulation of fluid in the pleural spaces]. AB - Altogether 345 patients with pleural effusion were investigated; 22 nosological entities were diagnosed. Of them four diseases (tuberculosis, metastatic cancer, pneumonia, and pleural mesothelioma) accounted for 79.7%. Failures of outpatient clinical investigation and late referral of patients to special diagnostic departments were noted. Possibilities to diagnose the type of disease on the basis of x-ray symptoms, clinical and laboratory tests and their combinations were analyzed. A necessity of the use of various types of biopsy with respect to an x-ray picture was recommended. Early thoracoscopic biopsy was indicated for progressive or stable pleural effusion of obscure etiology. PMID- 2270655 TI - [X-ray diagnosis of isolated tuberculous lesions of the bronchi]. AB - There are cases of isolated affection of the bronchial tree by tuberculosis leading to a separate form of tuberculosis. However, bronchial tuberculosis is rarely diagnosed in practice that can be accounted for by difficulties to differentiate it from other diseases. Specific affection of the small bronchi is noted more commonly. Three types of tuberculous lesions of the bronchial tree are singled out on the basis of an x-ray picture. PMID- 2270656 TI - [Characteristics of the x-ray picture of pulmonary tuberculosis in alcoholics]. AB - Tuberculosis prevalence among alcoholics is high, and pathomorphological and clinical manifestations of the disease are marked. Altogether 84 chronic alcoholics with pulmonary tuberculosis (the 1st group) and 100 tuberculosis non alcoholic patients (100 controls--the 2nd group) were investigated. X-ray signs of the disease progression, more prevalent changes and more frequent multiple disintegration cavity of larger size are noted in the 1st group. During x-ray investigation of such patients emphasis must be laid on a search for disintegration cavities and bronchogenic dissemination. PMID- 2270657 TI - [Optimization of computed tomographic studies during the diagnosis of chronic nonspecific lung diseases]. AB - A comparative study was made of computerized tomograms of 115 patients, of them 78 suffered from nonspecific chronic pulmonary diseases (chronic bronchitis, bullous emphysema, spontaneous pneumothorax, and fibrosing alveolitis), and 37 patients were healthy. Of all transverse sections the most informative ones were defined, and anatomical reference points were determined for. A conclusion was made that computerized tomograms at 5 most informative levels were sufficient to diagnose changes in each of the lung segments in their diffuse affection. CT standardization was shown to have the same advantages as standardization of layins in routine tomography of the lungs, facilitating comparison over time and reducing radiation exposure of a patient. PMID- 2270658 TI - [Differential diagnosis of deforming bronchitis and the peribronchial form of central lung cancer]. AB - Bronchofibroscopy was performed in 4736 patients in the Moscow Endoscopic Center (S. P. Botkin Hospital) over the period of September 1984-December 1987. Central lung cancer was diagnosed in 139, of them peribronchial tumor growth was determined in 15. Deforming bronchitis was diagnosed in 283 patients, 23 of them were admitted to hospital with the diagnosis of central lung cancer. Differential diagnosis of peribronchial central lung cancer and deforming bronchitis is based on findings of a combined study including roentgenography, tomography, bronchofibroscopy with biopsy for subsequent cytological and histological investigation. PMID- 2270659 TI - [Clinico-roentgenologic diagnosis of disseminated and diffuse lung diseases]. AB - The results of clinical and x-ray investigations of 398 patients with disseminated pulmonary lesions were analyzed. Two groups were identified: patients with interstitial type of lesions (101) and patients with focal type of lesions (297). Proceeding from roentgeno-morphological correlations, the authors presented specified roentgeno-semiotics of 10 nosological entities with the syndrome of pulmonary dissemination. The possibilities of optimization of differential diagnosis of disseminated pulmonary lesions were shown basing on combined (clinical, functional and roentgenological) investigation. PMID- 2270660 TI - [Digital processing and densitometry of tomograms in central lung cancer]. AB - Additional information on an x-ray picture of peribronchial changes in tumorous and non-tumorous lesions of the lungs were obtained in 54 patients (40 with bronchogenic, mostly central cancer and 14 with chronic inflammatory diseases) in order to study roentgenological symptomatology before and after computerized processing of tomographic images using a method of linear filtration. Image processing with the measurement of densitometric indicators provides additional information for the estimation of bronchial affection by tumor infiltration. The same method can be of value for the detection of early signs of lung cancer in patients with peribronchial changes of obscure etiology. PMID- 2270661 TI - [Possibilities of the x-ray diagnosis of posttraumatic fat embolism]. AB - The paper is concerned with some data, obtained during a study of case histories and x-ray findings of 12 (0.1%) of 9260 patients treated over the last 10 years in a traumatology department at a regional hospital for various traumas. Posttraumatic oil embolism was diagnosed in these 12 patients during their life. Of them 2 patients were women, and 10 men aged 20 to 74, and 7 patients were under 30. Five patients died. Open fracture was registered in 4 patients, closed fracture--in 7 patients, and contusion of the soft tissues--in one. Two cases were presented as an example. A conclusion was made of a possibility of the effective diagnosis and treatment of this severe posttraumatic complication at a provincial hospital. PMID- 2270662 TI - [A computer-assisted study of the effect of gravitation on the functional state of the lungs]. AB - Gravitation influence on lung function was investigated in 115 patients and 21 healthy persons. Changing of an examinee's position from vertical into a horizontal one causes changes in lung function in health and disease. Characteristic features of lung function were determined for each group of examinees in order to improve the diagnosis and differential diagnosis of bronchial cancer and nonspecific chronic pulmonary diseases with a similar x-ray picture. A study of pulmonary ventilation and blood supply of the lungs in vertical and horizontal postures in Hodgkin's disease patients led to a conclusion that irradiation of patients seemed more effective in a phase of deep breath. It made it possible to reduce radiation exposure of healthy parts in a zone to be irradiated. PMID- 2270663 TI - [Optical image processing in the analysis of the structural elements of the x-ray picture of the adult respiratory distress syndrome]. AB - The paper is devoted to the potentialities of aposterior image processing in adult patients with the respiratory distress-syndrome (RDS). Thirty one cases of optical processing of radiograms were analyzed. Pulmonary changes were absent in 10 persons of the control group. The authors described spatial and frequency characteristics of the structural elements of an x-ray picture of RDS (change of interstitial tissue, the state of pulmonary markings, micro-atelectases, edematous and small hemorrhagic parts). The localization of disease is mostly peripheral. The authors paid attention to probable criteria of differential diagnosis between RDS and other conditions, manifesting themselves in clinically acute parenchymatous respiratory insufficiency (lung edema, acute pneumonia, thromboembolism of the pulmonary artery). PMID- 2270664 TI - [Computed tomographic picture of the mediastinal lymph nodes in health]. AB - The results of CT investigations of the chest of 100 patients without changes in the mediastinal and pulmonary organs were used to describe a picture of different groups of unchanged mediastinal lymph nodes, to compare visualization of normal lymph nodes in x-ray and CT studies, to provide data on the frequency of their visualization and sizes. PMID- 2270665 TI - [An educational management system for the postgraduate training of physician radiologists]. AB - The paper is devoted to the development of a system of program-oriented postgraduate education of radiologists based methodologically on acquiring professional knowledge and skills. Educational goals were adapted for each subject area. Matrix analysis and plotting of a logical structure graph were used for a choice of the final goals of education. The subject matter is in full accord with the educational goals, based upon the qualification characteristics of radiologists. The developed and published methodological materials make it possible to control the students' activities during extracurricular training and practical work in x-ray units and at seminars. Directed text control is used for the estimation of efficacy and correction of education. PMID- 2270666 TI - [The analysis of diagnostic errors in patients with lung diseases in a general therapeutic ward]. PMID- 2270667 TI - [The diagnosis of pulmonary aspergillosis]. PMID- 2270668 TI - [A case of disseminated lung lesions in trichomoniasis]. PMID- 2270669 TI - [A case of a rare localization of a neurofibroma]. PMID- 2270670 TI - [A case of a lipoma of the chest wall penetrating into the interlobar fissure]. PMID- 2270671 TI - [Two cases of accessory superior cardiac bronchi]. PMID- 2270672 TI - [Determination of the degree of displacement of the mediastinal organs]. PMID- 2270673 TI - [A case of an unusual metastasis of cervix cancer to the lungs]. PMID- 2270674 TI - [A bronchogenic cyst adhering to the diaphragm]. PMID- 2270675 TI - [A pioneer of roentgenology--the Ukrainian professor I.P. Puliui]. PMID- 2270676 TI - A comparison of the nucleotide sequence homologies between isolates of the Andean and ordinary strains of potato virus S and their relationship to other carlaviruses. AB - Sequence homologies between the RNAs of five isolates of the ordinary strain of potato virus S (PVSo), four isolates of the Andean strain (PVSA), potato virus M(PVM), and the type member of the carlavirus group, carnation latent virus (CLV), were compared using cDNA solution hybridization. A high degree of homology (90-100%) was detected between the majority of PVSo and PVSA isolates, but lower levels of homology (less than 10%) were observed between PVS, PVM, and CLV. PMID- 2270677 TI - The plaintiff's lawyer: a physician's best friend? PMID- 2270678 TI - Medicare report on physician payment reform. PMID- 2270679 TI - How to respond to a PRO quality inquiry. PMID- 2270680 TI - Mohs micrographic surgery. AB - Mohs micrographic surgery has been highly successful in treating skin cancers that grow in a contiguous manner. The technique requires removal of involved tissue in thin layers and histographic mapping to pinpoint residual tumor. This process is repeated until all of the tumor is resected. This allows 100 percent of all margins to be examined and is very tissue conservative, attributing to its unsurpassed cure rates and excellent cosmetic results. Since it is done as an outpatient procedure under local anesthetic, it also is safe and efficient. PMID- 2270681 TI - Malignant melanoma. AB - The yearly number of patients with malignant melanoma presenting in the United States is increasing at an alarming rate. Unprotected sun exposure appears to be a major cause for this rise, and appropriate protection will hopefully reverse this worrisome trend. PMID- 2270683 TI - West Virginia Medical Journal 1990 index volume LXXXVI. PMID- 2270682 TI - Pneumocystis carinii pneumonia. AB - Pneumocystis carinii (PCP) pneumonia is the most common pulmonary infection associated with the acquired immunodeficiency syndrome (AIDS). Patients at risk for PCP have defects in T lymphocyte function and include cancer and transplant patients who are on immune suppressing agents and corticosteroids. In West Virginia, PCP accounted for 53 percent of pulmonary infections in 144 cases of AIDS from 1984 to May 1990. Nationally, at least 100,000 cases of PCP are projected for the early part of this decade. Patients with PCP may present with non-specific symptoms. The chest X-ray frequently shows diffuse bilateral infiltrates but may have atypical features. Definitive diagnosis should be established using sputum staining and various bronchoscopic techniques. Trimethoprimsulfamethoxazole and IV pentamidine are the most efficacious agents for treatment, and monthly aerosolized pentamidine is recommended for prophylaxis. Further basic science and clinical research on the biology of the P. carinii and its response to treatment strategies in HIV and non-HIV related infections is urgently needed. PMID- 2270684 TI - [A new serotype of Salmonella IIIb]. AB - An enterobacterium culture, S3188, providing with Salmonella biological characteristics, except exhibiting indole positive reaction, was isolated from the intestinal content of reptile a snake. It utilized malonate, did not ferment dulcitol, it attacked lactose promptly, and ONPG positive. H antigens appeared diphasic. By cross agglutination and absorption tests, it was demonstrated that the antigenic formula of this strain is 53:1, Z13:e, n,(Z15)... It was found to be a new serotype of Salmonella IIIb. PMID- 2270685 TI - [Analysis of cellular fatty acids of Enterobacteria species by gas chromatography mass spectrometry]. AB - Cellular fatty acid compositions of 15 Enterobacteria were analyzed by gas chromatography-mass spectrometry(GC-MS). About 30 fatty acids were detected in chromatograms, and 13 of them were chemically identified, e.i. C11:0, C12:0, C13:0, C14:0, C15:0, 2OH-C14:0, 3OH-C14:0, C16:1, C16:0, aC17:0, delta C17:0, C18:1 and C18:0. The major cellular fatty acids in all fifteen species were C16:0, C18:1, C15:0, C14:0, C16:1, C13:0, 3OH-C14:0 and C18:0. The cellular fatty acids of Enterobacteria species were characterized by normal straight-chain saturated acids and monounsaturated acids, of which the most abundant fatty acid was C16:0. 3OH-C14:0 was found in all strains of Enterobacteria, whereas 2OH C14:0 was only found in strains of Serratia species. Other unknown compositions also would have been certain characteristics for bacteria. The present paper would provide some of useful reference data for chemotaxonomy and molecular microbiology of Enterobacteria. PMID- 2270686 TI - [The relationship of Sindbis virus assembly and the viral protein 6K with intermediate filaments]. AB - The relationship of Sindbis virus (Sbv) assembly with intermediate filaments was studied by means of whole-mount and DGD embedment-free technique of EM together with the procedure of gentle extraction. In the early stage of Sbv infection, the "virus assembly center" was suspended in the intermediate filament network. In the late stage, the assembling and assembled virus nucleocapsids were associated with intermediate filaments. It is presumable that the virus nucleocapsids may move from the "virus assembly center" to cytoplasmic membrane along the intermediate filaments. Further study using immunolabelling technique indicated that the nonstructural protein 6K of Sbv was probably associated with intermediate filaments as well. PMID- 2270687 TI - [Physico-chemical and enzymological properties of beta-lactamase from Bacteroides fragilis]. AB - Bacteroides fragilis 55 from clinical specimens was selected at random for beta lactamase investigation of physico-chemical and enzymological properties. The enzyme was characterized as a cell-associated cephalosporinase with some penicillinase activity, the molecular weight of the enzyme being 43,000 and the pI 4.95. It could be inhibited by cefoxitin, PCMB, carbenicillin, sulbactam, clavulanic acid and cloxacillin. The optimum pH and temperature for enzyme reactions have been found to be 7.2 and 37 degrees C, respectively. The analysis of amino acid composition and parameters of enzyme kinetics has been described. PMID- 2270688 TI - [Electron microscopic observations on Pseudomonas cocovenenans]. AB - A strain of food-poisoning bacterium has been isolated by Jin Jiexiang (1963) in China from the fermented cornflour that has gone bad. These pathogenic microorganism has been identified and named Pseudomonas by Zhao Naixin in 1988, which is the same species as P. cocovenenans. The characteristics of them were conformed to these of the species P. cepacia of section 2 of the genus Pseudomonas. In view of the fact that the fine structures of the above mentioned three strains of Pseudomonas have not been described yet, we decided to observe them with electron microscope. Results indicate there are many things in common among the three strains, such as: appearing short rods, 0.6-0.8 microns in diameter by 1.5-2.0 microns in length, one polar multiflagella; non-pili, non capsules, non-endospores; containing intranuclear inclusions (electron-dense bodies or concentric laminae bodies), accumulating intracytoplasmic PHB granules; forming filaments, minicells and bizarrecells; producing extracellular cellulose like materials by the three strains have not been reported previously. PMID- 2270689 TI - [Degradation of acetonitrile by Acinetobacter sp. 51-2]. AB - A strain of Acinetobacter sp. 51-2 was capable of degrading acetonitrile and utilizing various nitrile compounds, such as propionitrile, butyronitrile, acrylonitrile and so on. The ability and speed of degrading acetonitrile were quite strong and fast. Strain 51-2 could degrade 25 g/L acetonitrile in 48 h by adapted cells. The efficiency of degrading acetonitrile was closely related to the conditions of culturing bacterial cells. The reaction temperature and present metals appeared to have a little effect on degradation of acetonitrile. PMID- 2270690 TI - [Gastroplasty in the treatment of morbid obesity]. AB - A series of 90 gastroplasty operations based on Eckhout's vertical banded procedure are described. The average weight loss at follow up 2 years postoperatively was 66%. There were no operative or late deaths nor any serious complications. The constricting Gore-Tex band had to be lengthened in 3 cases of outlet stenosis and shortened in another 3 cases of stomal dilatation. In one case the patient failed to lose weight due to a large initial pouch volume. PMID- 2270691 TI - [The effect of meniscectomy on the strength of the femoral quadriceps muscle after more than 3 years]. AB - This paper investigates the strength of the quadriceps extensor femoris following partial meniscectomy by means of arthrotomy. Measurements were carried out on 30 patients using a velocity-controlled dynamometer. Follow-up ranged from three to twelve years. On clinical examination 17 patients revealed atrophy of the quadriceps, amounting to 1 cm in 12 patients and up to 2 cm in 5 patients. The average difference in muscular strength between the operated leg and the non operated one totalled 11% in the cases of 1 cm atrophy and 19% in the 2 cm cases. Those patients who presented with no atrophy on the operated leg had an average loss of 4% in muscular strength, which is within the normal range. In addition, an interrelationship was established between measurements carried out at different angular velocities and the extent of quadriceps atrophy. The high percentage of patients showing a weakness of the quadriceps extensor femoris after a long follow-up period is most likely due to the severing of proprioceptors during surgery and to inadequate or lacking postoperative physiotherapy. PMID- 2270692 TI - [The application of electronic data processing in a cornea bank]. AB - In the eye bank of the second department of ophthalmology a computerized data base system was implemented for registration, documentation and analysis of all data on corneal donors and recipients. The aim was to reduce the necessity of handwritten forms and to increase safety of documentation. In addition, programs for automated HLA matching and digital image analysis for corneal endothelium have been developed. PMID- 2270693 TI - Rational use of antibiotics in the critically ill patient. AB - Despite the advent of newer broad-spectrum antibiotics, infection in critically ill patients still is associated with significant morbidity and mortality. For these patients, who frequently receive inappropriate and excessive empiric antibiotic therapy, it is important to develop rational drug usage criteria. Current economic forces, including personnel shortages and the effects of diagnosis-related groups, are also a critical factor in this patient population. Criteria for rational antibiotic selection are based on patterns of infection and knowledge of the pharmacokinetic and pharmacodynamic properties of individual antibiotics. The development and use of treatment protocols, or algorithms, will provide quality patient care for the lowest overall cost. PMID- 2270694 TI - Assessing the nutritional needs of the critically ill patient. AB - Because critical illness often creates a vigorous metabolic response to permit the repair of injured tissues, nutritional considerations are essential in the medical management of the critically ill patient. Individuals with seemingly adequate endogenous nutritional reserves may rapidly develop complications of starvation. Nutritional supplementation is essential; however, critically ill patients may not readily tolerate nutritional support. Calories may need to be withheld until the patient is able to tolerate and utilize nutritional support. Once the decision to initiate nutritional support is made, nutritional status, level of stress, metabolic condition, and vital organ function influence the patient's nutritional requirements. An assessment of the patient's metabolic condition provides data useful in determining the need for supplemental electrolytes or macronutrients. These data also provide information regarding vital organ function, which is necessary for utilization of the fuel and substrate. Aggressive monitoring and judicious nutritional supplementation will afford the critically ill patient the best chance of recovery. PMID- 2270695 TI - Use of H2-receptor antagonists in children. AB - H2-receptor antagonists (H2RAs) have evolved into the mainstay of anti-acid therapy for pediatric patients, replacing antacids and other modes of therapy. Much of the experience and data used for therapeutic decisions in children, however, have been extrapolated from adult studies. Ranitidine and cimetidine have been studied most extensively in the adult and pediatric populations. Both raise gastric pH and achieve other therapeutic endpoints; however, cimetidine appears to have a greater frequency of both adversed effects and drug interactions. H2RAs are the preferred agents for prevention of stress ulcers, ulcer disease, and reflux esophagitis in the pediatric population. PMID- 2270696 TI - Sclerotherapy for esophageal varices. AB - Endoscopic injection sclerotherapy (EIS) frequently is used for patients with esophageal varices, both for controlling acute hemorrhage and for prophylaxis. An old technique, interest in EIS increased when other methods did not improve patient outcomes. Clinical trials of EIS for acute hemorrhage demonstrated efficacy and improved outcome, although some researchers disagree with these findings. Recent data on prophylaxis with EIS fail to support the value of EIS for this indication. Ethanolamine oleate compares favorably with other sclerosing agents, and is the only one currently approved for EIS. The intravariceal method is used more frequently than the paravariceal method because it has better efficacy and can be performed more rapidly. The percentage of patients developing significant complications from EIS may be as high as 15 percent; common complications include retrosternal pain, pyrexia, and sepsis. EIS is currently an important clinical tool in the management of esophageal varices. PMID- 2270697 TI - Pathophysiologic changes in the critically ill patient: risk factors for ulceration and altered drug metabolism. AB - Virtually all patients who are under the physiologic stress of an intensive care unit (ICU) are vulnerable to stress-related mucosal damage and ulceration. Although clinically significant hemorrhage from stress ulceration occurs in only 5-20 percent of patients in the ICU, the associated mortality is greater than 50 percent. The pathophysiologic mechanisms of stress ulcer are not well understood; however, a number of risk factors such as intraluminal gastric acidity and mucosal ischemia have been implicated. To prevent the development of stress ulcers and subsequent complications, it is important to identify and correct these underlying risk factors. Improving mucosal blood flow (i.e., fluid resuscitation and low-dose dopamine) and providing adequate nutritional support are invaluable adjuncts in minimizing the risk of stress ulcer formation. The use of pharmacologic prophylaxis controls the gastric acidity and prevents the formation of stress ulcers. The potential for drug-induced adverse effects and drug-drug interactions are of particular concern in the care of critically ill patients. Multiple organ system dysfunction or failure, malnutrition, fluid and electrolyte abnormalities, as well as the use of multiple pharmacologic agents predispose these patients to alterations in drug pharmacokinetics, drug-induced adverse effects and drug-drug interactions. These changes may alter the pharmacodynamic response to therapy and must be considered when designing drug dosage regimens for critically ill patients. PMID- 2270698 TI - [The activities of surgeon Erwin Gohrbandt (1890-1965) on behalf of the Berlin University, the city's municipal council and the Berlin Surgical Society]. PMID- 2270699 TI - [Opinion on "The problem of listeriosis in childhood" by J. Kulz and H. Krebs in Z. Arztl. Fortbild. 84 (1990), 81-84]. PMID- 2270700 TI - [Ethical-judicial aspects in house calls]. PMID- 2270701 TI - [The problems of chronic health disturbances and diseases from the family physician's viewpoint]. PMID- 2270702 TI - [Topodiagnosis and differential diagnosis of speech and speech-related functional disorders]. PMID- 2270703 TI - [Neurological intensive care in a convalescence hospital--check lists for diagnostic strategy and therapy]. PMID- 2270704 TI - [Chronic pancreatitis. 1. Classification, etiology and pathomorphology]. PMID- 2270705 TI - [Antimicrobial chemotherapy of sick children in nurseries. Longitudinal study of children in nurseries over a period from 1981 to 1987]. PMID- 2270706 TI - [Analysis of the prescription and utilization of chemotherapeutic agents by pediatricians in ambulatory care in the Leipzig district. 1. Analysis of prescriptions of therapeutic agents]. PMID- 2270707 TI - [Quinidine-induced syncope--an example of the arrhythmogenic effect of anti arrhythmia agents]. PMID- 2270708 TI - [Chronic cranial subdural hematoma following lumber spinal fluid collection--a case contribution]. PMID- 2270709 TI - [Development and status of application of disease classifications in general medicine]. PMID- 2270710 TI - [Primary (essential) hypertension in childhood and adolescence]. PMID- 2270711 TI - [Chronic pancreatitis. 2. Clinical aspects and complications]. PMID- 2270712 TI - [Chronic pancreatitis. 3: Diagnosis and therapy]. PMID- 2270713 TI - [Analysis of prescriptions and utilization of antimicrobial chemotherapeutic agents by pediatricians in ambulatory care in the Leipzig district. 2: Analysis of the use of certain chemotherapeutic agents]. PMID- 2270714 TI - [Physiotherapy in airway diseases in childhood]. PMID- 2270715 TI - [Assessment of effectiveness in the treatment of patients with pain]. PMID- 2270716 TI - [The consequences of avoidable causes of death on life expectancy]. PMID- 2270717 TI - [The concept of research in general medicine]. PMID- 2270718 TI - [The system of self-administration by the General Medical Council of the Federal Republic of Germany]. PMID- 2270719 TI - ["Passer RUSTicus Linnaei" Johann Nepomuk Rust (1775-1840)--a Prussian medical official of the time of Schinkel]. PMID- 2270720 TI - [The structural prerequisites for the temporal support of neural activity]. PMID- 2270721 TI - [The thermodynamic approach to a scrutiny of the Purkinje effect and related phenomena]. PMID- 2270722 TI - [Neurotrophic factors secreted from the central nervous system]. PMID- 2270723 TI - [The formation of early species-specific behavior. The role of environmental factors]. PMID- 2270724 TI - [The after reactions of the auditory system neurons]. PMID- 2270725 TI - [Kindling as a model for the formation of behavioral disorders]. PMID- 2270726 TI - [The structural-functional organization of the connections in the system for the central regulation of visceral functions]. PMID- 2270727 TI - [Current status of surgery for abnormalities in newborn age and infancy]. AB - Own experiences about the modern standard of malformation surgery in newborns and young babies are demonstrated. Progress in prenatal diagnosis, perioperative management, operative strategy and operative technique improved the prognosis. Necessary is optimal interdisciplinary cooperation of all participants and special responsibility of the surgeon. PMID- 2270728 TI - [Surgery in esophageal atresia. Anatomical and functional aspects]. AB - The first successfully operated newborn with esophageal atresia dates back more than 55 years. During this period the concept of the unity of structure and function for surgical treated malformations has been retained. Primary anastomosis offers the best prerequisites. Main life threatening complications are leakage of the anastomosis, anastomotic strictures and gastroesophageal reflux. Avoiding vital complications the aim of undisturbed function can be achieved by appropriate surgical methods. The report describes own experiences over the past 20 years. PMID- 2270729 TI - [Duplication of the intestinal tract]. AB - Twelve duplications of the alimentary tract in eleven children are reviewed. There was a predominance of the spheric type of duplication as well as the neonatal group of children with clinical sign of tumour in most cases. There were no major problems in resection of spheric duplications but tubular type cases afforded different procedure in each case. Three cases with associated atresias were noted. There was one death related to gastric duplication. PMID- 2270730 TI - [Changes in the diagnosis and therapy of invagination]. AB - The alterations in diagnosis and therapy of intussusception in infants is described in 155 cases from 1978-1989. The primary diagnostic procedure is the abdominal sonography. It is followed to 1988 the attempt of hydrostatic reduction by barium enema and now the pneumatic reduction. The rate of success with conservative treatment was finally over 80%. Primary operative treatment is only necessary in the rare cases with signs of perforation of intestine or of peritonitis. PMID- 2270731 TI - [Bladder exstrophy. Treatment results over 27 years]. AB - Between 1960 and 1988 47 patients with bladder exstrophy were attended. 7 various operative procedures were applied. 3 patients died postoperatively, 37 of the 42 patients would be examined after 1 11/12 to 27 years. All patients with ureterosigmoidostomy exhibited electrolyte disturbance and metabolic acidosis. Patients with sigmoid conduit, rectal bladder and bladder reconstruction had unremarkable findings. The uretero-enterostomy anastomotic region was endoscopically essentially unremarkable. The control of continence was from satisfactory to good, and there was not absolute incontinence. X-ray investigation revealed both distinct and indistinct changes. The psychic and social stress was more serious in childhood than in adulthood. PMID- 2270732 TI - [Surgical heritage. Chronicle of inguinal hernia surgery in children with reference to the experience of the Surgical Department of the University Pediatric and Outpatient Clinic Leipzig 70 years ago]. PMID- 2270733 TI - Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. I. Influencing the biotope by means of metabolic drift mutants of Escherichia coli. AB - Through the selection of spontaneous metabolic drift mutants (selection marker RifR) of an Escherichia coli strain (O6:H2 SmR) of known settling capacity in conventional mice, it was attempted to obtain clones with positively optimized in vitro characteristics, which may exert a promotive influence upon the in vivo colonizing behaviour. Using 512 drift mutant strains (E. coli O6:H2 SmR RifR) we were able to establish positive optimizations, at an over-aleatory rate, for each of the in vitro characters tested (haemagglutination capacity of rabbit, guinea pig, and fowl erythrocytes; overgrowing power of mouse-adapted wild-type E. coli strains; formation of biomass with exclusive utilization of dextrose, lactose, fructose, adonitol, salicin, rhamnose, mannose; multiplying power; quantitative motility; and capacity to synthesize mucus). A higher settling rate (larger number of animals in which the test strain shared greater than or equal to 50% of the Enterobacteriaceae population than that obtained with the initial strain) could be established for one out of the 62 clones tested in vivo (a rise from 20% to 55%). The higher settling rate was associated with combinations of various functional parameters and not with an improvement of any of the individual functions. Despite the increase in settling rate relative to the number of experimental animals used in these studies, it was not generally possible to obtain a more than 3 days' dominance of the test strain within the lac+ Enterobacteriaceae. This is considered to be due primarily to the incipient synthesis of secretory IgA. PMID- 2270734 TI - Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. II. Influencing the biotope by means of geographically unrelated Escherichia coli strains. AB - An effective increase in the rate of colonization can be accomplished, in analogy with the pathogenetic mechanism of what is known as travelers' disease, through the administration of geographically unrelated strains. As compared to Escherichia coli strains isolated in the GDR, metabolic drift-optimized and Ethiopian strains showed an increase from 20 to 50%. It was not, however, possible to maintain a greater than or equal to 50% share in the population of Enterobacteriaceae over a period of more than up to three days. Immunologic mechanisms are considered to be responsible for this. PMID- 2270735 TI - Effect of chlorpromazine (CPZ) on the course of LCM virus infection in mice with developed and undeveloped immune system. AB - The cellular immune response to lymphocytic choriomeningitis (LCM) virus in germfree adult and conventional (Cv) suckling mice with undeveloped immune systems and in Cv adult mice with developed immune systems was suppressed by a single large, sublethal dose of the calmodulin antagonistic chlorpromazine and stimulated by a 100-times smaller dose administered intraperitoneally one day before the intracerebral virus infection. CPZ thus exerted a two-directional dose dependent immunomodulatory effect in mice with both undeveloped and developed immune system. PMID- 2270736 TI - The effect of methicillin on the fatty acid composition of total polar lipid in methicillin resistant Staphylococcus aureus. AB - The effect of two concentrations of methicillin on the fatty acid (FA) distribution in intracellular total polar lipid (TPL) of the log-phase cultures of a methicillin resistant Staphylococcus aureus strain No. 5814R was studied during a period of 2 h. Half the MIC of methicillin (= 1000 micrograms/ml) caused 18.6% increase in branched-FAs and a same decrease in straight-FAs, while one MIC (= 2000 micrograms/ml) of the drug induced a moderate change in those of TPL. The ratio of branched-FAs to straight-FAs increased from 1.24 to 1.56 in the presence of 1/2 x MIC of methicillin and reduced from 1.24 to 0.87 in the presence of 1 X MIC of the antibiotic. In TPL of the control cultures it gradually decreased from 1.24 to 0.77. It is concluded that under the effect of methicillin, FA composition of TPL in methicillin resistant cocci does not change as dramatically as in methicillin sensitive ones indicating lipid synthesis in methicillin resistant S. aureus to be less sensitive to the action of methicillin than in methicillin susceptible strains. This may contribute to the resistance against the lytic effect of the drug. Membrane lipid properties seem to be involved in the mechanisms of methicillin resistance. PMID- 2270737 TI - Nonspecific resistance-enhancing activity of zymosan in experimental bacterial infections. AB - The nonspecific resistance-enhancing activity of zymosan on experimental bacterial (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus) infections was investigated. Zymosan, being of very low toxicity, significantly enhanced nonspecific resistance to the above bacteria. The enhancement was the most pronounced 2 to 5 days after zymosan treatment. PMID- 2270739 TI - Revision of the validity of CAMP tests for Listeria identification. Proposal of an alternative method for the determination of haemolytic activity by Listeria strains. AB - The validity of CAMP tests with Staphylococcus aureus and Rhodococcus (Corynebacterium) equi as defined for Listeria identification was revised. This characterization method appeared to be unreliable for two reasons: first, a positive CAMP test with R. equi is not specific for Listeria ivanovii as Listeria monocytogenes (and Listeria seeligeri) give also a clear positive reaction; second, doubtful reactions could be observed with S. aureus when assaying haemolytic and non-haemolytic Listeria strains (possibility of false negative and false positive results; subjectivity of the interpretation). The use of a Microplate technique previously described instead of CAMP tests is proposed for the reliable demonstration of the haemolytic character of Listeria in the routine identification of these organisms. PMID- 2270738 TI - Influence of the measles virus on the proliferation and protein synthesis of aortic endothelial and smooth muscle cells. AB - To clarify whether some viruses could influence the different functions and membrane permeability of the aortic cells, we have examined in a model experiment the in vitro effect of the measles virus on the aortic endothelial and smooth muscle cells. The aortic cells infected with the virus failed to reveal gross cytopathic effect. Occasionally, however, syncytium formation and nuclear inclusions were observed. In infected endothelial cells lysosome containing viral nucleocapsids were seen. The early phase of measles virus replication inhibited the proliferation of endothelial cells of all species tested, while uniformly stimulated the replication of the smooth muscle cells relative to the control. In bovine aortic endothelial and smooth muscle cells the protein synthesis had been suppressed by the 4th to 6th hours postinfection. The results indicate that measles virus infection may be among the risk factors of atherosclerosis. It may damage endothelial cells by altering the cell membrane permeability and could induce proliferation of aortic smooth muscle cells. PMID- 2270740 TI - Association of virulence markers with animal pathogenicity of Escherichia coli in different models. AB - Employing chicken and several strains of mice, different routes (intraperitoneal, subcutaneous) of infections and isogenic pairs of strains, association of virulence markers with animal pathogenicity was studied in Escherichia coli. Mouse virulence of avian strains was less significant than the lethality for chicks of human strains. LD50 in various animals did not differ significantly. Strains with antigen K1 were more virulent for mice than their K1- derivatives. Loss of haemolysin (Hly), mannose resistant haemagglutinating capacity or antigen K5 less markedly decreased the virulence. As opposed to other virulence factors, increased virulence of K1+ strains could also be demonstrated in mouse sepsis assay based on bacterial counts in the liver. Loss of Hly alone did not influence the persistence in the liver, however, these strains killed less mice. Aerobactin acts together with other factors, it is not per se a virulence factor. In organotropic experiments 19 strains out of 36 belonging to serotypes O7:K1:H-, O18:K1:H-, O78:H- and spontaneously agglutinable K1+ cultures, caused ophthalmitis with purulent discharge, and 4 out of 22 strains that belonged to serotype O78:H- induced uncoordinated movement of mice. Because of its special organotropic affinity to the brain and as it caused two epidemics of meningitis among newborns in Hungary, serotype O78:H- has a special pathogenic property and differs from other O78 strains that were isolated in other countries. PMID- 2270741 TI - Listeria isolation from foods of animal origin. AB - Microbiological examination of Listeria, isolated from foods of animal origin was carried out during the period 1986-1987. A total of 642 samples from chicken, beef and pork raw meats, fish, eggs and from the environment were investigated. Using the cold technique, Stuart's transport medium, tryptose broth and Ralovich's medium, 76 Listeria strains of serogroup 1 and 2 were isolated. PMID- 2270742 TI - Comparison of adenoviral hexon polypeptides (monomers) and of native hexons (trimers) by SDS-polyacrylamide gel electrophoresis. AB - Purified hexons of 27 serotypes of human, simian, bovine and avian adenoviruses were analysed by SDS-PAGE. The apparent molecular weights of hexon polypeptides calculated by comparison with 5 non-hexon and 3 sequenced hexon polypeptide markers ranged from 98 kDa (for bovine adenovirus Ad bos7) to 118 kDa (for simian adenovirus Ad sim13; SV36). A stability of native hexon capsomers (trimers) in SDS at room temperature permitted us to resolve native (trimeric) hexon by SDS PAGE and to distinguish them from denatured (monomeric) hexon polypeptides by electrophoretic mobilities. Hexon trimer bands with slow mobility in SDS-PAGE (unlike hexon monomer polypeptide bands) retained native hexon antigenicity as revealed by immunoblot analyses. Possible applications of simultaneous analyses of hexon trimers and monomers by SDS-PAGE are discussed. PMID- 2270743 TI - Incidence of MS during two fifteen-year periods in the Gothenburg region of Sweden. AB - The average annual incidence of definite and probable MS in Gothenburg was re investigated. For 1950-1954, 1955-1959 and 1960-1964 it was 4.2, 4.2 and 4.3/100,000/year. For the five-year periods between 1974 and 1988 it was 3.0, 2.7 and 2.0/100,000/year. If possible MS was included, the corresponding incidence for 1950-1964 was 5.2, 5.3 and 5.1, and for 1974-1988 it was 3.9, 3.9 and 4.3/100,000/year. Neurological methods and diagnostic criteria were constant throughout the period. The 1950-1964 incidence was based on personally investigated cases, while the 1974-1988 incidence was based partly on review of Gothenburg neurology records. It is concluded that there has been a significant decrease in the incidence of MS in this area. However, the notified decrease may partly be explained by alterations in the case ascertainment procedure. Since the Swedish measles vaccination program started in 1971, the occurrence of measles has been declining and has practically ceased during the 1980s. The time when a possible influence of mass vaccinations against childhood diseases on MS incidence can be monitored is discussed. PMID- 2270744 TI - A Dutch family with autosomal dominant pure spastic paraparesis (Strumpell's disease). AB - Families with "pure" hereditary spastic paraparesis of late onset have rarely been reported. Since the original article by Strumpell in 1880, many "complicated" forms of the disorder have been reported, and the question as to whether a "pure" form exists still arises from time to time. We present a Dutch family with "pure" hereditary spastic paraparesis, involving 15 affected members in three generations. The mode of inheritance was autosomal dominant, with onset of clinical signs in the fourth or fifth decade. Severity of the disease was mild; only a few of them became chairbound in the end. There were no sensory symptoms. Mild sphincter disturbances were mentioned by six patients. A review of the reports on Dutch families is given and arguments in favour of the existence of "pure" hereditary spastic paraparesis are discussed. PMID- 2270745 TI - Cerebral blood flow and metabolism following subarachnoid haemorrhage: cerebral oxygen uptake and global blood flow during the acute period in patients with SAH. AB - Forty-eight patients with subarachnoid haemorrhage were studied with repeated rCBF and CMRO2 measurements. Cortical rCBF was measured using xenon-inhalation technique. CMRO2 was calculated as AVDO2 x CBF. When first studied the 29 conscious patients showed relative hyperaemia with CBF at 50 ml and reduced CMRO2 at 2.17 ml. In the following week CBF decreased to 41. CMRO2 remained reduced and constant. The 19 unconscious patients showed initially pronounced reduction in CMRO2 to 1.26, followed by gradual increase to 1.73 in 4-5 days. Simultaneously CBF increased from 18 ml to slightly above 30 ml. In the conscious patients the early reduction in CMRO2 and the concomitant luxury perfusion may be explained by global ischaemia because of very high ICP at the time of the haemorrhage. The reduced CBF in the unconscious group could be due to increased ICP, as ventricular drainage increased CBF to levels of relative hyperaemia as demonstrated in one case. As no decrease in CMRO2 was seen during the first 2 weeks, it is suggested that ischaemia at the time of aneurysm rupture is the most important single factor in reduction of global CMRO2. PMID- 2270746 TI - Changes in spinal cord function evaluated by evoked potentials and spinal cord blood flow from a lateral retraction post-cervical laminectomy. AB - We induced ischemia and stretching by retraction of the spinal cord after laminectomy in 12 anesthetized mongrel adult cats, recorded spinal motor evoked potential (SpMEP) and spinal somatosensory evoked potential (SpSSEP) and determined the spinal cord blood flow (SCBF). The results showed a correlation between progressive deterioration of the function and a decrease in SCBF. Comparing the abnormal findings of both the peak and interpeak latencies in evoked potentials, useful data were more frequently obtained using SpSSEP than SpMEP. Factors involved in their deteriorations seem to be a moderate ischemia by compression, and a stretching by the retraction of the spinal cord. From these results, we conclude that SCBF and SpSSEP are important for monitoring the impulse propagation during retraction of the cervical cord. PMID- 2270747 TI - Long-term follow-up of MS: disease activity detected clinically and by MRI. AB - Prospective clinical and magnetic resonance imaging (MRI) studies were performed over a period of 2-3 years on 51 MS patients. Comparing cerebral MRI and neurological evaluation for sensitivity in detecting disease activity, follow-up MRI turned out to be superior to standardized clinical assessment. In particular, an interval during which the clinical findings remain stable may not necessarily indicate that there is no florid inflammatory activity during this time. The morphological progression demonstrated a preference towards periventricular localization around the posterior horns of the lateral ventricles, and non periventricularly in the frontal white matter. Longitudinal MRI studies of the disease activity can be an aid in obtaining a more definite diagnosis. Patients having had the disease for a longer period showed a more rapid clinical and morphological progression. Clinical progression and an increase in periventricular involvement were observed more often in the primary unremitting progressive form of MS than in the relapsing-remitting form. PMID- 2270748 TI - Circulating glycoconjugates in CSF of meningioma patients. AB - This study investigated whether tumor-associated gangliosides or glycoproteins may be markers for meningiomas in CSF. The concentrations of a number of gangliosides and sulphatide were determined with specific monoclonal antibodies and cholera toxin B-subunit in a thin-layer chromatography overlay technique. As compared to a reference group of 10 individuals (mean age 50 +/- 14 years), the CSF samples from 7 meningioma patients (mean age 55 +/- 12 years) were found to contain significantly increased concentrations of ganglioside GD3 [II3(NeuAc)2 LacCer], one of the major gangliosides in meningioma tissue specimens. Sulphatide was significantly increased in 6 of 7 patients. Tumor-associated glycoproteins detected by the lectin Ricinus communis 1 in meningioma tissue specimens, but not in normal human brain tissue, were also found in the CSF of the meningioma patients. An early diagnosis of meningiomas might be achieved by the combined assay in CSF of ganglioside GD3 and glycoproteins with Ricinus communis lectin. PMID- 2270749 TI - Effect of high doses of essential fatty acids on the postviral fatigue syndrome. AB - Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms. The preparation given contained linoleic, gamma linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3 point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits. At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome. PMID- 2270750 TI - Evoked potentials and CSF-immunoglobulins in MS: relationship to disease duration, disability, and functional status. AB - In 100 MS patients, BAEP and tibial SEP abnormality rates increased significantly with disease duration and clinical disability. VEP correlated non-linearly with disease duration, and median nerve SEP correlated with disability. In multifactorial analysis, however, BAEP correlated significantly only with clinical brainstem and cerebellar signs. These results suggest that evoked potentials correlate more strongly with neurological status of the functional subsystems than either overall disability or disease duration. These findings indirectly suggest that evoked potentials may be useful monitors during large therapeutical trials in MS patients. PMID- 2270751 TI - Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias. AB - Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF. PMID- 2270752 TI - MS in the Faroe Islands and the possible protective effect of early childhood exposure to the "MS agent". AB - Epidemiologic data on multiple sclerosis (MS) in the Faroe Islands have been interpreted by the original investigators as supporting a particular infectious disease model. They suggest that MS occurs as a late consequence of extended exposure to an infectious agent which cannot be transmitted to subjects younger than 11 years of age. However, the Faroes data may better fit an alternate model, in which MS results from delayed primary exposure to an infectious agent which more commonly produces benign illness and protection against MS in subjects who are exposed in infancy or early childhood. PMID- 2270753 TI - Changes in adhesion efficiency and vimentin distribution of fibroblasts from familial Alzheimer's disease patients. AB - Cultured fibroblasts from familial Alzheimer's disease patients were characterized. Familial Alzheimer fibroblasts showed the same appearance by phase microscopy and the same growth rate with the control fibroblasts cultured from the age-matched healthy control subjects. Fibroblasts cultured from familial Alzheimer's disease patients showed decreased efficiency in adhesion to substrata in limited periods. While 80% of the control fibroblasts finished adhesion within 30 minutes incubation, only 30% of Alzheimer fibroblasts completed adhesion within the same period. When fibroblasts from familial Alzheimer's disease were kept under serum-free media more than ten days, they showed a unique aberration of vimentin fiber distribution, while other cytoskeletal fibers were remained intact. It is indicated that fibroblasts cultured from patients with familial Alzheimer's disease can be used to study pathological processes which affect the cytoskeletal organization in the fibroblasts as well as in the cells of the central nervous system. PMID- 2270754 TI - Does Swedish amateur boxing lead to chronic brain damage? 1. A retrospective medical, neurological and personality trait study. AB - Sweden banned professional boxing in 1969 and has also considered banning amateur boxing. We therefore analysed possible chronic brain damage in 47 former amateur boxers who started their careers after the introduction of stricter Swedish amateur boxing rules. The boxers were compared with three control groups--25 soccer players, 25 track and field athletes and 19 conscripts. All athletes were interviewed about their sports career, medical history and social variables. They then underwent a physical and a neurological examination, including a mini-mental state examination. Personality traits were investigated and related to their platelet MAO activity in the athletes as well as in the conscripts. No significant differences were found between the groups in any of the physical or neurological examinations. All had a normal mini-mental state examination. Thus, results from these test methods did not reveal any signs of chronic brain damage from Swedish amateur boxing. Neither were any significant differences found with regard to platelet MAO activity, while significant differences were found in some of the social and personality traits variables. PMID- 2270755 TI - Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis. AB - Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS. PMID- 2270756 TI - Trigeminal sensory impairment after soft-tissue injury of the cervical spine. A quantitative evaluation of cutaneous thresholds for vibration and temperature. AB - The cutaneous sensibility for vibration and temperature in the trigeminal skin area was examined with quantitative methods in 30 patients with a previous soft tissue injury of the cervical spine. Sixteen patients with chronic and disabling symptoms had significantly increased thresholds for vibration over the ophthalmic (p less than 0.001) and mandibular (p less than 0.01) divisions of the trigeminal nerve compared with 14 without symptoms. Temperature thresholds were measured in all three divisions of the trigeminal nerve, and were significantly increased in all three compared with controls (p less than 0.001 in ophthalmic division, p less than 0.01 in maxillary and p less than 0.05 in mandibular divisions). The impairment of vibration and temperature sensibility in the trigeminal skin area in patients with chronic symptoms after soft-tissue injury of the cervical spine indicates damage to the central trigeminal system in upper spinal cord segments and ponto-medullary levels of the brainstem. PMID- 2270757 TI - Vibration sensitivity thresholds: methodological considerations. AB - Vibration sensitivity thresholds were studied in 12 healthy volunteers using 25, 50, 100 and 250 s-1 stimulus frequencies from an instrument with automated and manual modes ('Vibra Mk II'). For the automated mode, a forced choice principle was adopted. All measurements were performed from both the knuckle of the IInd metacarpophalangeal joint and the medial malleolus on four successive days. In addition, a conventional tuning fork method for vibration sensitivity was applied. The results show high interindividual and intraindividual variation in all measurements. The threshold values measured by the automated system were significantly lower than those by manual system at all frequencies. The largest variation was seen at 250 s-1 and the most uniform values at 100 s-1. There was a clear difference between the values from knuckle and medial malleolus, the values in the foot being lower. There was no learning effect. Clear age-related increase in vibration thresholds was observed. Conventional tuning fork-method showed clear differences in vibration sensitivity between hand and foot, in accordance with computer assisted method. The higher sensitivity of the automated method compared to the manual makes this the method of choice, although further investigations to finish the method and to build up a broader reference material is desirable. PMID- 2270758 TI - No increased relapse frequency in acute Guillain-Barre syndrome after plasma exchange. AB - Relapse frequency in 23 patients with acute Guillain-Barre syndrome (GBS) treated with plasma exchange (PE) was studied. Fifteen patients showed clear improvement, and 4 patients some improvement during the PE period, whereas 4 patients did not improve in immediate connection to the PE treatment. During the follow up time of 6-96 months (mean 36 months), only one of the 23 patients had a relapse, which appeared after 3 months. This relapse frequency is similar to that reported as the natural history of GBS, and thus, we can not verify the recently reported increased relapse frequency of GBS after PE. PMID- 2270759 TI - Prostaglandins: a key factor in human labor. PMID- 2270760 TI - Role of prostaglandins in pre-eclampsia. PMID- 2270761 TI - Which types of perinatal events are predictable? A look at a risk score model. AB - This study describes the association of a risk factor model for complicated delivery, perinatal morbidity and perinatal mortality with each of various types of delivery complications, types of perinatal morbidity and causes of perinatal mortality. The material comprises a total cohort, 4,066 pregnant women with singletons in a Danish county, and their newborn infants, of whom 494 (12%) had clinical morbidity during the first 5 days of life; 28 (0.7%) died perinatally. A set of 20 risk factors, identifiable before pregnancy, at any time during the pregnancy or at term, was devised by joining existing models for prediction of complicated delivery and of perinatal morbidity and mortality. Metabolic and disproportion-related events were well predicted by the model, inertia-related ones less so, and placental conditions not at all, except for abruption. All types of neonatal morbidity (except sepsis) were well predicted, as were deaths. The strongest predictors of perinatal death were signs of hydramnios (RR = 16.1) and growth retardation (RR = 7.2). The 20 risk factors affected 43% of the population, predicting 57% of the unfavorable perinatal events. PMID- 2270762 TI - Pregnancy outcome after female infertility in Kuwait. Comparison of medical and surgical treatment. AB - During a 4-year period, 163 patients conceived after treatment of their infertility due solely to a female factor. They were divided into two groups, 108 patients treated medically (Group 1) and 55 treated surgically (Group 2). At the time of conception, the mean age in Group (1) was 24.9 +/- 5.7 years while in Group (2) it was 31.2 +/- 6.1 years. The difference was statistically significant (p less than 0.01). The duration of infertility prior to pregnancy and the treatment-to-pregnancy interval were both significantly longer in Group (2) (p less than 0.05). The rates of miscarriage, multiple pregnancy, and preterm labor were higher in Group (1), though the differences were statistically not significant. In contrast, the rate of ectopic pregnancy was significantly higher in Group (2) (p less than 0.05), as was the need for elective cesarean section (p less than 0.01). Despite these differences, both groups had nearly the same perinatal outcome. PMID- 2270763 TI - Hypertension as a risk factor in pregnancies complicated by systemic lupus erythematosus. AB - To study the occurrence and significance of pregnancy-associated hypertension and pre-eclampsia in systemic lupus erythematosus (SLE), we studied retrospectively 34 pregnancies in 27 SLE patients in 1981-87. Eleven pregnancies (32%) were hypertensive (group A). The remaining 18 patients during their 23 pregnancies had a normal blood pressure (group B). Previous nephritis was slightly more common in the hypertensive group (54.5% vs. 26.1%, NS). Preeclampsia was present in seven of the pregnancies (21%) and of whom four were superimposed. Flare-ups of the disease were more common in the non-hypertensive group (30.4%) than in group A (9.1%) (NS). Duration of pregnancy was the same in the two groups. Intra-uterine growth retardation was present in 27.3% of the pregnancies in group A and in 13.0% of group B (NS). Fetal loss occurred only in 2 patients of the non hypertensive group; one patient had exacerbation of SLE and the other (with two stillbirths) high anticardiolipin antibodies. Our data suggest that pregnancy associated hypertension and pre-eclampsia do not cause increased fetal loss in pregnancies affected by SLE. There seem to be other factors that are more important, such as antiphospholipid antibodies and flare-ups of the disease. PMID- 2270764 TI - Physiological values of cysteine and metalloproteinase activities in chorionic villi. AB - Lysosomal cysteine proteinases (cathepsin H, B + L) and metalloproteinase (MMP7 ase) activities were measured from early gestational period (6-12 weeks) in frozen, non-cultivated chorionic villi. The mean activity of cathepsin H was 50.99 mU/mg protein, of cathepsin B + L, 71.16 mU/mg protein, and of MMP7-ase, 16.16 mU/mg protein. The MMP7-ase enzyme activities showed a correlation with gestational age. There was a significant correlation between the activities of cathepsin H and MMP7-ase. PMID- 2270765 TI - Control of fetal membrane prostaglandin E2 production by bacteria. AB - The effect of bacteria on the production of prostaglandin E2 (PGE2) and PGE2 metabolites by fetal membranes has been investigated. Live bacteria stimulated a large increase in the levels of PGE2 metabolites, but only a small increase in the levels of PGE2 on the fetal side of the membranes. No significant changes in the levels of PGE2 or its metabolites were found on the maternal side. Bacteria may therefore stimulate PGE2 production by fetal membranes during short-term incubations, but it seems that the metabolic capacity of the chorion was so high that no change in PGE2 levels was detectable on the maternal side of the fetal membranes. This was confirmed by the finding that less than 1% of 3H-PGE2 added to the fetal side of the membrane reached the maternal side without being metabolized. PMID- 2270766 TI - Does physical exercise influence the frequency of postmenopausal hot flushes? AB - The frequency of moderate and severe hot flushes was investigated in a group of women (n = 142) who took part in organized physical exercise on a regular basis, and a control group of all women 52 and 54 years old in the city of Linkoping, Sweden (n = 1,246). Only women with natural menopause and without a history of hormonal replacement treatment were statistically compared in the study. It appeared that moderate and severe vegetative symptoms with hot flushes and sweatings were only half as common among the physically active postmenopausal women (21.5%) as in the control group (43.8%). Although this could be due to a positive selection of these physically active women, it might also be due to the fact that exercise may affect the mechanisms that elicit hot flushes in peri- and postmenopausal women. PMID- 2270767 TI - Single-dose oral fluconazole versus single-dose topical miconazole for the treatment of acute vulvovaginal candidosis. AB - OBJECTIVES: To compare efficacy, safety and patient preference of a single oral dose of 150 mg fluconazole with a single intravaginal dose of 1200 mg miconazole in vaginal candidosis. To investigate the effect of treatment on Candida colonization of throat and rectum. DESIGN: Double-blind, double-dummy, parallel, randomized trial. Ninety-nine patients with symptomatic and mycologically verified candidosis were given 150 mg fluconazole with an intravaginal dummy, or 1200 mg miconazole with an oral dummy. Patients with an inadequate short-term response were given a second dose. RESULTS: At each visit a patient self assessment and an investigators' global assessment were recorded, and cultures were set up. Adverse events were recorded and laboratory tests were performed. Clinical cure or improvement (investigators' assessment) was obtained in 100% (short-term) and 95% (long term) of the fluconazole group and in 94% and 90%, respectively, of the miconazole group. Patients considered the treatment excellent or good in 81% (short-term) and 88% (long-term) in the fluconazole group and in 84% and 76%, respectively, of the miconazole group. Mycological cure was achieved in 98% (short-term) and 73% (long-term) of the fluconazole group and in 96% and 82% respectively in the miconazole group. The differences in results were not significant. Both treatments significantly reduced the number of positive rectal cultures: neither treatment had a significant effect on throat cultures. Four percent of the patients preferred intravaginal therapy. CONCLUSION: A single dose fluconazole is as safe and effective as a single dose of miconazole. PMID- 2270768 TI - Serum half-life of the tumor marker CA 125 during induction chemotherapy as a prognostic indicator for survival in ovarian carcinoma. AB - Patients (n = 72) with newly diagnosed non-mucinous ovarian carcinomas, FIGO stages IIC-IV, and CA 125 levels raised when starting chemotherapy were followed both by serial serum CA 125 tumor marker determinations during induction chemotherapy and by second-look operation after 4-6 cycles of chemotherapy. Patients with complete response at the second-look operation (n = 19) had an estimated survival of 75% 59 months after the operation, compared with 22% in the 53 patients with persisting disease (p = 0.0004). Patients (n = 23) with a serum CA 125 half-life shorter than 16 days during induction chemotherapy had an estimated survival of 68% 59 months after the second-look operation as compared with 18% in 49 patients with a CA 125 half-life of more than 16 days (p = 0.003). Thus both second-look operation and serial CA 125 measurements fairly accurately predicted the patient survival, although the groups of patients identified by the two methods differed slightly. There was a strong correlation between the second look results and the residual tumor after the primary operation. Interestingly, this association could not be found for tumor marker pattern, which could mean that this is an independent prognostic factor. PMID- 2270769 TI - Pathologic torsion of the pregnant uterus. AB - A case of 90 degrees C dextro-torsion of the uterus in the 36th gestational week is reported. The case was asymptomatic and was discovered at cesarean section carried out because of transverse lie following rupture of the membranes. Mother and child were discharged in perfect health. PMID- 2270770 TI - Non-obstructive cecal dilatation and perforation after cesarean section. AB - A case of non-obstructive cecal dilatation and perforation after cesarean section is reported, with a review of the literature on the diagnosis and management of this entity. Fifteen cases have been described. Attention is called to this rare complication and to the accompanying pseudo-obstructive syndrome, the diagnosis of which is important in order to avoid cecal perforation. Non-obstructive cecal dilatation is a life threatening complication to cesarean section, and immediate surgical intervention is important. PMID- 2270772 TI - A large labial adhesion following normal delivery. AB - Labial adhesions seldom occur following vaginal delivery. We report the case of a large labial adhesion forming after an uneventful pregnancy and normal delivery in a multiparous patient. PMID- 2270771 TI - Pneumothorax in pregnancy. AB - Since 1957, only 15 cases of isolated spontaneous pneumothorax in pregnancy have to our knowledge been reported in the English literature. The treatment of pneumothorax in pregnancy is more difficult than in non-pregnant patients. A case is reported and therapy discussed. PMID- 2270773 TI - Leiomyoma of the ovary. AB - Ovarian leiomyoma is a rarity. Usually it is not associated with any clinical symptoms. Macro- and microscopically it is indistinguishable from the uterine leiomyoma. Treatment consists of simple removal of the tumor. The possible histogenesis of this tumor is reviewed. It is concluded that the ovarian leiomyoma probably originates from the smooth muscle cells of the ovarian blood vessel or from the smooth muscle fibers near the attachment of the ovarian ligament. PMID- 2270774 TI - Synergistic effect of transforming growth factor beta and fibroblast growth factor on DNA synthesis in chick growth plate chondrocytes. AB - Transforming growth factor beta and fibroblast growth factor are mitogens for chick growth plate chondrocytes. TGF-beta stimulated a 3.5-fold increase, and FGF a 13.5-fold increase in the rate of thymidine incorporation after a 24 h exposure. TGF-beta and FGF were synergistic in chondrocytes, causing a 73-fold stimulation in thymidine incorporation compared with control. This synergistic response was not dependent upon the simultaneous presence of both mitogens. Sequential exposure of chondrocytes to TGF-beta and FGF in either order reproduced in large part the synergistic interaction observed when both growth factors were present simultaneously. The time required for induction of the subsequent synergistic response was brief and, in the case of TGF-beta, corresponded to the time required for [125I]TGF-beta receptor binding. EGF and PDGF were not mitogenic for chondrocytes, and neither of these factors enhanced the response of the cells to either TGF-beta or FGF. Finally, TGF-beta and FGF did not, either alone or in combination, elevate intracellular cAMP levels. These results emphasize the importance of examining growth factor effects in the context of other growth regulators. Furthermore, this specific and dramatic synergistic stimulation of thymidine incorporation may provide a useful tool in elucidating the mitogenic mechanism of the individual growth factors. PMID- 2270775 TI - Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes. AB - A 59-year-old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. Serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25-dihydroxyvitamin D3 and osteocalcin levels were low. Histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25-dihydroxyvitamin D3 and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine antagonist. PMID- 2270776 TI - Influence of calcium load on absorption fraction. AB - True calcium absorption was studied as a function of the size of the ingested load in healthy adult women, under meal conditions and at loads ranging from 15 to 500 mg calcium. Fractional absorption was highly inversely correlated with the logarithm of load (P less than 0.001). At the lowest loads, absorption averaged 64.0% and at the highest, 28.6%. The parameters of the best-fit relationship permit reasonably precise calculation of the impact of various calcium dosing and dietary strategies. PMID- 2270777 TI - Calcium absorptive consistency. AB - Calcium absorption efficiency was measured two or three times each in 74 premenopausal and 142 postmenopausal women under conditions predicted to alter absorptive performance. A woman's absorptive consistency was evaluated across differing loads, differing intervals, and substances of differing intrinsic absorbability. In all these circumstances there was a statistically significant correlation between a woman's absorption under differing test situations accounting for up to 60% of the variance typically found in cross-sectional studies. For example, when the same substance but at differing load levels was tested three times over an 8 week period, various coefficients of correlation ranged from +0.773 to +0.849 (P less than 0.001). Even over intervals as long as 5 years correlation of absorption fraction within individuals remained significant (r = +0.487, P less than 0.001). PMID- 2270778 TI - Effects of progesterone on postovariectomy bone loss in aged rats. AB - The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone-treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Progesterone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protective effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of postmenopausal osteoporosis. PMID- 2270779 TI - Sex differences in peak adult bone mineral density. AB - Osteoporotic fractures are more common in women than men. Although accelerated bone loss following the menopause is recognized as of major importance, it is generally considered that a lower peak adult bone mass in females also contributes to their increased risk of osteoporosis in later life. To examine potential sex differences in peak adult bone mass we studied 29 pairs of dizygotic twins of differing within-pair sex in whom the female twin was premenopausal (mean age 37 years, range 21-55). Bone mineral density (BMD, g/cm2) was measured at the lumbar spine and femoral neck by dual-photon absorptiometry; 22 pairs also had BMD measured in the distal and 21 pairs in the ultradistal radius by single-photon absorptiometry. There was no significant difference in usual dietary calcium intake or tobacco consumption between the twin pairs. Consistent with accepted dogma, BMD at both radial sites were higher (+27%) in the males than their female cotwins. In contrast, there was no sex difference (male versus female) in BMD (mean +/- SEM) in the femoral neck (0.96 +/- 0.02 versus 0.97 +/- 0.03), and surprisingly, the females had a greater lumbar spine BMD than their male cotwins (1.19 +/- 0.03 versus 1.26 +/- 0.03, p less than 0.05). This difference was observed despite the fact that the males were taller (p = 0.033). If the femoral neck BMD values in the females were corrected for this difference in BMI, their values (0.99 +/- 0.03 g/cm2) were significantly higher than those in their male cotwin (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270780 TI - Presystemic 24-hydroxylation of oral 25-hydroxyvitamin D3 in rats. AB - The metabolism of 25-hydroxyvitamin D3 (25-OHD3) was compared following its intracardial or gastric administration. The rats were deprived of calcium and vitamin D. A mixture of radiolabeled (0.3 microCi) and stable (2 micrograms) 25 OHD3 was given as a single dose. After 24 h the rats given the dose by gastric tube had significantly lower serum concentrations of 25-OHD3 and 1,25 dihydroxyvitamin D3 [1,25-(OH)2D3] than those injected intracardially. In contrast, serum 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was much higher in the rats given the 25-OHD3 dose by gastric tube (6.2 nmol/liter +/- 1.3 SD, n = 7) compared to the intracardial group (0.9 nmol/liter +/- 0.5, p less than 0.001). The preceding results were based on specific radioactivity of metabolites. The same findings were obtained by reanalyzing the samples using conventional competitive binding assays for 25-OHD3, 1,25-(OH)2D3, and 24,25-(OH)2D3. The results show that orally administered 25-OHD3 is partly metabolized to 24,25 (OH)2D3 presystemically. PMID- 2270781 TI - Effects of androgens on parathyroid hormone and interleukin-1-stimulated prostaglandin production in cultured neonatal mouse calvariae. AB - In this study we show direct inhibitory effects on prostaglandin E2 (PGE2) production by the androgens, testosterone (T) and dihydrotestosterone (DHT), in cultured neonatal mouse calvariae. After 24 h of preculture with or without androgens, bones were treated with bovine (1-34)-parathyroid hormone (PTH) or recombinant human interleukin-1 alpha (IL-1). During preculture androgens decreased PGE2 release only in those experiments in which control PGE2 was high. PTH increased medium PGE2 9-fold at 24 h, and 10(-11) M T inhibited this increase by 50%. Treatment with IL-1 for 24 h increased medium PGE2 19- to 22-fold, and 10(-10) M T and DHT inhibited this increase by 60 and 70%, respectively. T did not significantly affect the PTH-stimulated release of previously incorporated 45Ca or alter the PTH inhibition of incorporation of [3H]proline into collagenase digestible protein. IL-1 stimulated 45Ca release by 60-80%, and small but significant reductions of 20-30% were seen with T and DHT. This study shows that T and DHT have direct effects on bone at physiologic concentrations, similar to our previous study in which PTH-stimulated PGE2 production in the same culture system was inhibited by physiologic concentrations of 17 beta-estradiol, and suggests that prostaglandins may mediate some of the effects of androgens in vivo. PMID- 2270782 TI - Leucine-rich sequence in osteoinductive factor. PMID- 2270783 TI - Comparison between classic-differential and automatic shunt functioning on the basis of infusion tests. AB - Infusion tests were performed in order to examine cerebrospinal compensatory ability in two groups of patients with impaired compensation, subjected to shunt implantation. The functioning of the classic differential shunts was compared to the automatically (Orbis-Sigma) functioning shunts. The reference group, with intact compensatory parameters is also presented. The influence of different types of shunts on the intracranial compensation ability was compared. Automatic shunts produce less decrease in the resorption resistance of CSF in the post shunted examination than the classic differential shunts. Classic differential shunts disturb the mono-exponential character of the pressure-volume relationship in a higher degree than automatic shunts. Shunt functioning models were proposed as well as the method of detection of eventual recovery to the normal resorption reserve. This method can be applied only to patients with automatic shunts. PMID- 2270784 TI - Regional cerebral blood flow in the pig after a localized cerebral contusion treated with barbiturates. AB - Regional cerebral blood flow determined with microsphere technique in anaesthetized pigs was measured before and after a localized cerebral contusion as well as after treatment with pentobarbital. No overall reduction in intracranial pressure or perfusion pressure was observed. Flow reduction due to pentobarbital was different in different regions with a high percentage change in the highly perfused basal structures and cortical grey matter except in the centre of the contusion where the reduction was half compared to the rest of cortical grey matter. Changes in white matter were less than in cortical grey matter but more pronounced than in the very high flow areas (choroid plexus and pineal gland). The accumulated change was greatest in the damaged region. Contralateral to the contusion, where a significant increase in flow was noticed after the contusion, there was a very low accumulated change in flow. In white subcortical matter underlying the contusion a similar low flow change was observed but this was not accompanied by as large an accumulated change as in grey cortical matter. At each fraction of injected pentobarbital a short-lasting increase in intracranial pressure and a reduction in mean arterial blood pressure was observed. The amplitude and the height of the intracranial pressure change was reduced during the pentobarbital injections. PMID- 2270786 TI - Prognosis in traumatic intraventricular haemorrhage. AB - Traumatic intraventricular haemorrhage (TVH) is rare. The clinical profile and prognosis in 16 patients with traumatic intraventricular haemorrhage after blunt head injury are evaluated. Majority of the patients (94%) had low Glasgow coma score (less than 8) on admission and none had a lucid interval. CT showed haematoma adjacent to the foramen of Monroe in 5 patients and localised to the frontal horn or the body of the lateral ventricle in six. The mortality was 62.5% in this subgroup of patients with head injury. Our findings are compared to those of previous reports in the literature. The poor prognosis of cases with TVH reflects the severity of trauma and general brain damage and is probably not related only to the intraventricular bleeding. PMID- 2270785 TI - Neurosurgical treatment of traumatic frontobasal CSF fistulae in 300 patients (1967-1989). AB - 300 patients with traumatic fronto-basal CSF fistulae were treated neurosurgically from 1967 to 1989, i.e. via a transcranial approach. An additional intracranial space occupying lesion, a direct open endocranium and/or a large basal brain hernia was found in 68%. The following aspects were discussed: progress in establishing the exact anatomical diagnosis, especially neuroradiological advances; questions of the indication for surgery; the problem of the optimal surgical approach. Both the cranial and the rhinological approach have advantages and disadvantages. Their indications only partly coincide, so that the choice of method depends especially on the individual pathology. Advances were made in recent years in terms of neurosurgery as well as of rhinology. The neurosurgical results could be improved, and postoperative complications have become rare after the cranial approach. Besides the optimal choice of the time of operation, the following factors are important: an adequate intracranial debridement; a microsurgical technique entailing as little damage to surrounding tissue as possible and various specially mentioned brain-protective measures. An optimal collaboration between the specialties involved is the basis for further progress. More attention must be paid to endocrinological problems in the future. PMID- 2270787 TI - On the management of neonatal tentorial damage. Eight case reports and a review of the literature. AB - From the history of 15 personal patients--8 reported here in extenso--and from 63 patients in the literature with the diagnosis of posterior fossa subdural haemorrhage during life, we discuss the possibility of detecting tentorial damage on computed tomography (CT) and ultrasound (US) scan. The association of a (peri)cerebellar haemorrhage with peritentorial bleeding around the straight sinus and a subdural haemorrhage between both occipital cerebral lobes is suggestive of tentorial laceration(s). Both coronal CT scan and sagittal US scan are very helpful in locating these haemorrhages near the falco-tentorial junction. The conservative management of one of our infants with very extensive but asymmetric posterior fossa haemorrhage, leading to resorptive hydrocephalus, is compared with both surgical and conservative treatment of patients from the literature. Two reasons that warrant neurosurgical intervention are: life threatening brain-stem compression--as in one of our own patients--and acute obstructive hydrocephalus. Craniotomy of the posterior fossa within the neonatal period does not prevent later-onset resorptive hydrocephalus. The communicating nature of this latter process is adequately demonstrated by lumbar isotope cisternography. Finally, neonatal posterior fossa subdural haemorrhage is one of the many causes of cyst-like structures behind the cerebellum. PMID- 2270788 TI - Epidural haematoma in the newborn infants: therapeutic consequences from the correlation between haematoma content and computed tomography features. A review. AB - Eight reported cases of neonatal epidural haematoma are reviewed. Special attention is directed at the correlation between the haematoma content and computed tomography (CT) features. Seven cases had a high density haematoma on CT, of which four showed liquid, one semi-liquid, one liquid and solid, and one solid haematoma. The low density haematoma in one case was liquid. These results suggest that evacuation of the epidural haematoma via percutaneous epidural tapping is warranted as the first line of treatment irrespective of high density on CT. PMID- 2270789 TI - Choroid plexus tumours in children. Review of 24 cases. AB - 24 cases of choroid plexus tumours (16 papillomas and 8 carcinomas) were observed in the Department of Paediatric Neurosurgery, Hopital des Enfants de la Timone, Marseille France between 1975 and 1989. The case records were reviewed and the clinical, surgical, and pathological results are presented here. 14 (58%) were infants and 10 (42%) of these were aged less than 1 year at presentation. In 11 (46%) the tumour arose in the lateral ventricle, in 7 (29%) it was located in the IIId ventricle, and in 6 (25%) the tumour was found in the IVth ventricle. 5 of the 8 carcinomas had their origin in the IVth ventricle. 17 cases (75%) required ventriculo-peritoneal shunt procedures before surgery of the tumour and in all these it was left in place post-operatively. One child required shunting de novo after removal of the tumour. A total excision was achieved in 20 children (83%) out of 23 operated upon. The operative mortality (mortality within one month of surgery) was 8%, the overall mortality was 25%. One child with a IIId ventricle papilloma died before surgery from a large gastro-intestinal haemorrhage. 5 children under the age of 3 years with carcinomas on the IVth ventricle died. The 3 children with supratentorial carcinomas are alive respectively 2 months, 8 years, and 13 years after treatment. Among 15 children with papillomas alive, 10 (67%) are neurologically intact and 5 (33%) have sequelae. PMID- 2270790 TI - About a very rare variation of the course and width of the vertebral arteries and the hypoglossal nerve. AB - Described are: 1. A very thin intracisternal part of the vertebral artery (0.9 mm). 2. A very rare course of the vertebral artery (dorsal to the hypoglossal nerve). 3. Rare anastomoses between the vertebral artery and the PICA. 4. A rare upwards coiling of the PICA and 5. The origin and prevertebral course of the vertebral arteries. PMID- 2270791 TI - Branches of the anterior communicating artery. Microsurgical anatomy. AB - The anterior communicating artery (ACoA) and its branches were examined in 22 human brains after injecting Indian ink or methylmethacrylate. The ACoA branches were divided into the small and the large. Small branches were from 1 to 5 in number (mean 2), and from 70 to 270 microns in diameter (mean 151 microns). Seventy-six percent of the branches originated directly from the ACoA. They tended to arise closer to the left than to the right anterior cerebral artery. Fourteen percent of them arose from the junctional site of the ACoA with the anterior cerebral arteries, and 10% from the site of origin of the subcallosal artery. Large branches were identified as the median artery of the corpus callosum, and the subcallosal artery, respectively. The former vessel was present in 9% of the patients, and the latter in 91%. The subcallosal artery was from 320 to 640 microns in size (mean 486 microns). It tended to arise from the middle of the ACoA. In spite of the very frequent anastomoses involving the ACoA branches, care must be taken to avoid injury to these important vessels during operations of the ACoA aneurysms. PMID- 2270792 TI - Brachycephalic, serrated curettes for anterior cervical spinal microsurgery. Technical note. AB - Modified spinal fusion curettes with two unusual features on the tip are described for anterior cervical procedures. The features are: 1) an elliptical, long sidewise ("brachycephalic") scoop at the tip and 2) a serration equipped on the distal scoop edge. These designs allow reliable manipulation and significant removal of the intervertebral space contents in the deep operative field under the microscope. PMID- 2270793 TI - Angiotensin converting enzyme inhibition, CBF autoregulation, and ICP in patients with normal-pressure hydrocephalus. AB - Fourteen patients with normal pressure hydrocephalus had the autoregulation of cerebral blood flow (CBF) and intracranial pressure (ICP) investigated. In 8 of the patients the effect of Captopril on ICP and CBF was also investigated. The mean arterial blood pressure (MABP) was 109 mmHg (intra-arterially), and ICP was 11 mmHg (intraventricularly). Changes in global CBF were estimated by the arterio venous oxygen difference method. The autoregulation of CBF was present in 13 of the patients (p less than 0.01). The lower limit of CBF autoregulation was 86% of the baseline perfusion pressure. One hour after 50 mg of captopril perorally, MABP was reduced 16 mmHg, and ICP and CBF were unchanged. The autoregulation was maintained and the lower limit was decreased 19 mmHg. Thus patients would be expected to benefit from captopril treatment in hypotensive anaesthesia. PMID- 2270794 TI - Magnetoencephalography. PMID- 2270795 TI - Principles of magnetoencephalography. PMID- 2270796 TI - Biomagnetic studies of peripheral nerves and skeletal muscle. PMID- 2270797 TI - Neuromagnetic instrumentation. AB - In considering what type of MEG system is needed, there are four main considerations: 1. Ambient magnetic noise at the intend site(s). The need to reject external noise will determine the need for a shielded room. Here, manufacturer's claims can be compared in terms of magnetic field sensitivities (BN/square root Hz) at the measurement site. There are several tradeoffs to consider. A relatively quiet environment may allow use of a less expensive eddy current-shielded room combined with second-derivative gradiometer coils. A more harsh environment might need an MSR, but a gain in sensitivity may be afforded by using first-derivative gradient coils. A truly hostile environment could require multiple eddy-current shields combined with an MSR using three or more layers of mu-metal. 2. Head coverage and spatial resolution. The number of channels will roughly determine the number of times the Dewar(s) must be moved to cover the entire region of interest. Until MEG systems are available that can cover the entire head, coverage will be an important factor. Spatial resolutions (related to the diameter of the pickup coils and their spacing) should be adequate for all intended measurements. 3. Required sensitivity. Since the objects to be studied are current dipoles, magnetic field sensitivities (in fT/square root Hz) are not appropriate. This should be in terms of sensitivity to a current dipole measured in ampere-meters (Eq. 10) as a function of depth below the bottom of the Dewar tail. 4. Data acquisition systems and system software. Major considerations include the following: At what rate is data to be gathered? What is the total amount of data to be gathered in a single session? Must the data be processed real-time? How is the data to be interpreted? How is the data to be displayed? By examining these factors, it should be possible to compare available systems for neuromagnetic measurements and determine which system is appropriate for your needs. PMID- 2270798 TI - Neuromagnetic studies of evoked and spontaneous activity in animals. PMID- 2270799 TI - Magnetoencephalography as a noninvasive tool for electrophysiological characterization of auras in classic migraine. PMID- 2270801 TI - Somatosensory evoked fields in magnetoencephalography. Basic principles and applications. PMID- 2270800 TI - Generators of visually evoked neuromagnetic responses. Spatial-frequency segregation and evidence for multiple sources. PMID- 2270802 TI - Short-latency evoked magnetic fields from the human auditory brainstem. PMID- 2270803 TI - Long-latency auditory evoked magnetic fields. PMID- 2270804 TI - Electroencephalographic and magnetoencephalographic studies of motor function. AB - Although a great deal has been learned from the study of scalp-recorded movement related potentials, the exact origin of the various components described above remains unclear, mainly because of the limited spatial resolution of the EEG and the consequent difficulty in predicting sources from the surface distribution of these components. The introduction of the MEG and source localization methods based on neuromagnetic recordings has provided a new means by which to study the cortical activation during movement in humans. The study of movement-related magnetic fields of the brain is still at an early stage of development. However, the data reviewed to date indicate that the MEG offers a promising means by which to study (noninvasively) cortical motor function. With regard to the data reviewed here, the following conclusions can be made: 1. Slow "readiness" magnetic fields can be recorded prior to a variety of voluntary movements and display a topography which indicates the activation of bilateral sources, even if the instructed movement is unilateral. Sources in the contralateral hemisphere appear as early as 0.5 sec before the movement and appear to be localized in the sensorimotor cortex. Consequently, the assumption of a contralateral source being the only or primary generator of the readiness potential, based on EEG data, must be tempered. 2. A large-amplitude "movement-evoked field" (occurring at a post EMG-onset latency of about 110 msec for finger movements) is probably the counterpart of the MP and appears to be the result of a dipolar source localized to the contralateral sensorimotor area. This source is probably the first sign of movement reafferent input to cortex. 3. Variability in the movement-evoked field across individuals, which are much more evident in MEG than in EEG, may reflect the summation of multiple sources active in the region of the sensorimotor cortex during movement onset (i.e., both pre- and postcentral generators). In some instances, it may be possible to extract simpler elements of these complex sources based on assumptions of temporal overlapping of pre-movement and movement evoked activity. PMID- 2270805 TI - Magnetoencephalography in the study of mental illness. PMID- 2270806 TI - Epilepsy research. NIH experience. PMID- 2270807 TI - Magnetoencephalography in clinical epilepsy studies. The UCLA experience. PMID- 2270808 TI - Italian contributions to magnetoencephalographic studies of the epilepsies. PMID- 2270809 TI - Magnetoencephalography in the study of stroke (cerebrovascular accident). PMID- 2270810 TI - The use of magnetoencephalography in neurology. PMID- 2270811 TI - Comparison of electroencephalography and magnetoencephalography. PMID- 2270812 TI - Localization of brain activity with electroencephalography. PMID- 2270813 TI - Localization of brain activity with magnetoencephalography. PMID- 2270814 TI - The inverse problem in electroencephalography and magnetoencephalography. PMID- 2270815 TI - Magnetic evoked responses. Comparison with electrical evoked responses. PMID- 2270816 TI - Modeling in magnetoencephalography. PMID- 2270817 TI - Preparing the educational interpreter. A survey of sign language interpreter training programs. AB - Despite rapid growth in the field of educational interpreting little is known about the formal training of educational interpreters. This gap in the research is the focus of this study. A questionnaire was sent to the directors of 50 interpreter training programs nationwide asking for information about their course work in educational interpreting and related areas; instruction in signed English systems; and the directors' opinions on certain ethical and professional questions facing the educational interpreter. The results suggest that graduates of interpreter training programs who obtain employment as public school interpreters are not adequately prepared. Training programs provide few courses on the education of deaf children, on the language systems used, and on issues specific to classroom interpreting. The directors of these programs overwhelmingly support the development of guidelines on the educational interpreter's role. They show some support for the "interpreter as tutor" role but are equivocal about the development of a special certification for educational interpreters. PMID- 2270818 TI - Cognitive processing and the development of concepts by deaf students. AB - An examination of experimental learning models revealed that they all refer to the critical component of processing. The authors define processing as an activity that is employed to encourage students to reflect, describe, analyze, and communicate in some way that which was recently experienced. The authors describe a cognitive processing hierarchy and show how it relates to the characteristics of hearing-impaired students. They also share techniques for designing and leading processing activities. PMID- 2270819 TI - Diagnosing a learning disability in a hearing-impaired child. A case study. AB - In the past, the learning problems of hearing-impaired children have been attributed solely to the child's hearing loss. A hearing impairment and its associated language deficit make it difficult to determine whether an underlying learning disability contributes to the hearing-impaired child's learning problems. This report describes a case study that used an interdisciplinary diagnostic approach to determine whether a hearing-impaired child had a learning disability and to determine the type of disability. The approach included teacher observation, standardized assessment procedures, interpretation, and subsequent recommendations. Applying this approach to various educational settings is also discussed. PMID- 2270820 TI - The parental experiences of mothers of adolescents with hearing impairments. AB - Adolescence is a difficult time in the life of any youth. In the hearing-impaired child it can be an especially stressful period. The mother, who in many families is the primary care giver, has probably put more of her time and energy into helping the child than any other individual. Familiarity with the thoughts and feelings of the mothers, then, should contribute to our understanding of the hearing-impaired adolescent. Yet, few studies have examined the experiences of mothers during this stage. In this study, five hearing mothers of hearing impaired adolescents were interviewed on their experiences in rearing a hearing impaired child. The information culled from these interviews and the subsequent analysis should help fill the void of knowledge on this aspect of the hearing impaired child. Using qualitative analysis of the mothers' experiences the researchers identified six major themes from the data collected in the interviews: (1) the mothers' personal growth, (2) the mother-child relationship, (3) parent-professional relationships, (4) concerns about educational programming, (5) the importance of fluent communications, and (6) support systems available to the mothers. Suggestions are made for parents and to help improve parent-professional relationships and the programs that serve the hearing impaired and their families. Areas for further research on the subject of rearing hearing-impaired adolescents are identified. PMID- 2270821 TI - Self-concept among hearing Chinese children of deaf parents. AB - This paper discusses a study of Chinese children in Hong Kong that compared the self-concepts of hearing children of deaf parents with the self-concepts of hearing children of hearing parents. The study was based on the responses to a questionnaire given to 42 deaf couples and their 70 hearing children, and 41 hearing couples and their 82 hearing children. It found no differences in the self-concepts of hearing children of deaf parents and hearing children of hearing parents. However, it did find that deaf parents had lower self-concepts than hearing parents. PMID- 2270822 TI - Iconicity and sign vocabulary acquisition. AB - This study was designed to investigate learning and retention of isolated sign vocabulary as a function of sign classification (iconic, opaque, or abstract). The subjects were 28 hearing college students naive to sign vocabulary. They were drilled with 30 signs from American Sign Language that had been classified as iconic, opaque, or abstract. Training was conducted using two different media: computer-assisted instruction and videotaped presentation. Performance scores for the three types of signs were significantly different. Scores were consistently higher for iconic signs, regardless of the training mode. The videotaped presentation mode produced the greatest consistency in scores. The results of this study support the notion that it is easier for beginning students of sign language to learn and retain iconic signs. PMID- 2270823 TI - Deafness simulation. A model for enhancing awareness and sensitivity among hearing educators. AB - Awareness of and sensitivity toward handicaps on the part of nonhandicapped faculty and staff in educational environments is vital for both students and faculty. Awareness and sensitivity can be gained in a variety of ways; however, coordinated efforts are usually more comprehensive and enhancing. At the Rochester Institute of Technology in the College of the National Technical Institute for the Deaf, a college for deaf students in Rochester, New York, the faculty development staff carried out a deafness simulation project for hearing faculty and staff. Rationale, a description of the project, and effective approaches for implementing and coordinating deafness simulation projects are presented below. PMID- 2270824 TI - The play behavior of hearing-impaired kindergarten children. AB - This exploratory study examined the cognitive and social play behaviors of hearing-impaired kindergarten children with regard to classroom instructional mode and communication strategies. Two classes were observed--one using sign communication and the other using an oral-based method of communication. Functional, constructive, dramatic, and social play behaviors were observed and documented. Statistically significant differences were found between the two groups of children with regard to social and dramatic play as well as with regard to levels of aggression. For example, children in the sign-based class demonstrated higher levels of social play behavior and lower levels of aggression than the children in the oral-based class. Guidelines and strategies to help children initiate and sustain play are suggested. PMID- 2270825 TI - Teaching idiomatic expressions. A comparison of two instructional methods. AB - Twenty hearing-impaired children enrolled in a state residential school for deaf students in a large south central U.S. city participated in a study that compared the efficacy of two instructional designs used to teach idiomatic expressions. One of the methods consisted of videotape presentations followed by classroom discussion, and the other consisted of extended classroom discussions. The children ranged in age from 13 to 16 years, with a mean age of 13 years, 11 months. Their reading grade level scores ranged from 1.9 to 6.9, with a mean of 3.5. Sixteen popular idiomatic expressions were selected and original scripts depicting the expressions were prepared and then performed by members of the local deaf acting club. Each expression was also captioned on the tape. At the conclusion of the filming, the skits were edited into two videotapes consisting of eight idioms each. The children were randomly assigned to one of two groups: the videotape group or the classroom discussion group. Both groups improved their understanding of the idioms significantly over the course of the study. However, improvement was significantly greater when the children received instruction under the videotape method. Tests given to the students 8 and 16 weeks after the experiment showed that they had retained the knowledge. PMID- 2270826 TI - HIV infection risk to health-care workers. AB - The risk of occupationally acquired human immunodeficiency virus (HIV) infection in exposed health-care workers has been estimated to be 0.5% after accidental needlestick with an HIV-contaminated needle. Needlestick injuries resulting in parenteral exposure to HIV-infected material are the most common reported cause of occupational HIV infection in health-care workers. With 60% of these exposures unpreventable even with strict adherence to current infection control procedures, it is necessary to develop technical changes in work protection in order to further reduce the risk. PMID- 2270827 TI - HIV infection risk to nonhealth-care workers. AB - As has been summarized above, the risk of casual contact transmission of HIV virus is remote. A review of these data should provide reassurance to both workers and management. No evidence exists for direct contact spread through shaking hands and nonsexual touching. There is also no evidence for indirect spread through contact with shared inanimate objects such as typewriters, telephones, computers, water fountains, rest rooms, dining facilities, exercise equipment, bathing facilities, spas, saunas, and swimming pools. In addition, there is no evidence to suggest the airborne spread of HIV, thus there should be no potential risk of transmission through air-conditioning units, air-handling systems, or by sharing the same office space with an infected individual. The fear of AIDS may lead to irrational beliefs and biased perceptions of risk. This, unfortunately, can sometimes lead to discriminatory and inhumane treatment of persons with AIDS. The best way to manage this potential problem in the workplace is through effective educational interventions. PMID- 2270828 TI - A case study of lead in drinking water: protocol, methods, and investigative techniques. AB - A comprehensive study was performed to determine whether lead (Pb) in drinking water exceeded acceptable levels at a manufacturing and research site. Recent research indicates the possibility of abnormal adolescent development if the mother's blood lead levels exceed 15 micrograms lead per dL of whole blood. Using Environmental Protection Agency (EPA) estimates of average consumption and ratios correlating the amount of lead consumed to blood lead levels, a level of 10 micrograms/L of lead in water was determined to be acceptable. Water samples were collected from each type of water cooler and from faucets in every bathroom on site. Samples were collected that represented worst case exposures. Novel methods were used to identify the source of lead at those locations that exceeded the acceptable limit for lead. Control techniques are discussed. A laboratory study was performed to determine if lead could be prevented from leaching into drinking water from existing plumbing systems by treating the system with carbon dioxide gas. PMID- 2270829 TI - Variability in protection afforded by half-mask respirators against styrene exposure in the field. AB - Concentrations of styrene were measured in the breathing zone and inside the facepiece of air-purifying half-mask respirators of 13 workers for three to six 1 hr periods while they were engaged in the production of fiberglass-reinforced products. These data were used to estimate the protection afforded by the respirators. In arriving at these estimates, it was necessary to correct the concentration measured inside the mask for pulmonary retention of styrene by the workers. Workers were classified as sprayers or as other production line workers not directly carrying out spraying operations. An analysis of variance showed no evidence of differences in the level of protection afforded by the respirators between the two job classes. A second analysis of variance showed that protection varied between workers as well as for a single worker during different wearing periods. The geometric standard deviation (GSD) between workers was 1.92, the common within-worker GSD was 2.93, and the total GSD was 3.51. One-half of a population of wearers with similar protection would be expected to experience long-term average workplace protection factors in excess of 44 and one-half below that value. The observation of between-worker and within-worker variability in protection indicates that both sources of variability have to be taken into account in the specification of maximum use concentrations. PMID- 2270830 TI - Filter and leak penetration characteristics of a dust and mist filtering facepiece. AB - The filtering facepiece, also referred to as a disposable respirator, is an extensively used type of respirator without an officially accepted fit testing method. This study describes an aerosol generator and a sampling train, which have been developed for investigating the aerosol penetration characteristics through the filter element and the face seal. Electrostatic attraction and impaction are the two primary filtration mechanisms for micrometer- and supermicrometer-sized aerosols, respectively. Filtration and flow dynamics were found to affect aerosol penetration in distinct ways that allow for the differentiation of the face seal leakage from the filter penetration. The slope of the aerosol size-dependent penetration curve potentially may differentiate the face seal leakage from filter penetration. PMID- 2270831 TI - Real-time measurement and control of waste anesthetic gases during veterinary surgeries. AB - Veterinary clinics are typically small businesses without access to sophisticated occupational safety and health programs that may exist for larger firms or hospitals. Exposures to waste anesthetic gases have been linked to a myriad of adverse health-related conditions. Excessive exposures to anesthetic agents are possible because many of the clinics use portable gas delivery carts that are not designed to capture waste gases. While scavenging systems are available to remove waste anesthetic gases, the cost may be prohibitive for smaller clinics and the effectiveness of these systems has not been fully established in veterinary clinics. The National Institute for Occupational Safety and Health (NIOSH) recommends limiting exposures to nitrous oxide (N2O) to a time-weighted average (TWA) concentration of 25 ppm and halogenated agents to 2 ppm. The NIOSH TWA is based on the weight of the agent collected from a 45-L air sample by charcoal adsorption over a sampling period not to exceed 1 hr. The NIOSH criteria state that, in most situations, control of N2O to the TWA as defined will result in levels of approximately 0.5 ppm of the halogenated agent. At present, no Occupational Safety and Health Administration (OSHA) permissible exposure level (PEL) exists for exposure to anesthetic agents; nor do specific recommendations exist for veterinary scavenging systems. Waste anesthetic gas exposures were determined using a modified MIRAN 1A at five veterinary clinics operating within the Morgantown, West Virginia, vicinity. For unscavenged systems of methoxyflurane and halothane, 1-hr time-weighted average exposures ranged from 0.5 to 45.5 ppm and 0.2 to 105.4 ppm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270832 TI - Arsenic levels in fingernails as a biological indicator of exposure to arsenic. AB - The analysis of urine, blood, and hair has been used previously to monitor occupational exposure to arsenic (As). Although arsenic is normally present in human fingernails (usually as a result of dietary factors), this study evaluated the potential use of levels of arsenic in fingernails as a biological indicator of occupational exposure to this element. Air samples and fingernail clippings were obtained from individuals with no exposure and high, medium, and low exposure. A washing technique, previously developed to remove exogenous arsenic from hair, was modified to wash the fingernail samples collected in this study. It was demonstrated that 98% of exogenous arsenic was removed from these nails. A high correlation coefficient (r = 0.89) was observed in a comparison of the mean air arsenic concentrations of each exposure group with corresponding arsenic levels in fingernails. From the data collected, an equation was derived to estimate the air arsenic exposure level for a worker from the arsenic content of fingernails: air arsenic concentration (micrograms As/m3) = 1.79 x fingernail arsenic level (micrograms As/g nail)-5.9. PMID- 2270833 TI - Stimulation and release of prostaglandins and thromboxane from macrophages by cotton dust associated lipopolysaccharides. AB - Decreases in the ventilation capacity of human lungs following the inspiration of cotton dust correlates more closely with the concentration of endotoxin in the dust than with any other parameter measured thus far. A lipopolysaccharide isolated from the endotoxin of Enterobacter agglomerans, a common bacterial contaminant of cotton fiber, stimulated isolated rat macrophages to produce and release prostaglandins 6 keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA2, and PGB2 and thromboxane B2. If in vivo human pulmonary macrophages respond in a similar fashion by releasing these arachidonic acid metabolites or their immediate precursors in response to stimulation by cotton dust associated lipopolysaccharides, some of the acute pulmonary changes observed in humans following inspiration of cotton dust could be caused by increased release of these biologically active compounds. Daily release of arachidonic acid metabolites at concentrations significantly above normal homeostatic levels could produce some of the pathophysiologic pulmonary changes observed in byssinotics. This paper reports the results of an experiment to quantitate arachidonic acid metabolite production following macrophage stimulation by E. agglomerans lipopolysaccharide. Procedures are described for the stimulation of macrophages by cotton dust associated lipopolysaccharide, for the separation and identification of arachidonic acid and its metabolites by high-performance liquid chromatography, and for the quantification of those products by radioisotope techniques. PMID- 2270834 TI - The high, medium, and low method--a better noise reduction rating? AB - This paper compares hearing protector attenuations calculated using National Institute for Occupational Safety and Health (NIOSH) method No. 1 ("long method") and the HML method. The study was done on 144 combinations of 12 noises and 12 protectors. In each case, the attenuation was calculated using each of the above methods. The difference between attenuations was used to define the accuracy of the high, medium, and low (HML) method. It was found that the attenuations calculated using the HML method are almost always lower than those calculated using the NIOSH method. However, the differences between both attenuations are well within the field noise level measurement errors. Consequently, the HML method appears to be an acceptable approximation of the NIOSH method, offering the additional advantage of being easier to apply. The higher accuracy of the HML method, when compared to the Noise Reduction Rating (NRR), makes is preferable for applications in industrial hearing conservation programs. PMID- 2270835 TI - Seeds of strategic and interactional psychotherapies: seminal contributions of Milton H. Erickson. AB - The life and work of Milton H. Erickson exerts a considerable influence upon the development of strategic and interactional psychotherapies. In this paper we trace the historical course of Erickson's impact in these areas from his early associations with Gregory Bateson and Margaret Mead through his contributions to the ideologies of Jay Haley and practitioners at the Mental Research Institute. We have identified seven philosophical and methodological realms which represent the incorporation of Ericksonian principles into strategic and interactional family therapy models. PMID- 2270836 TI - Literalism and hypnosis: hypnotic versus task-motivated subjects. AB - To extend previous literalism research with hypnotized and simulating subjects, we compared literalism rates of hypnotized, highly hypnotizable subjects (N = 12) with nonhypnotized, task-motivated subjects (N = 12) who were also highly hypnotizable. Six questions of the type used by Erickson (e.g., "Do you mind telling me your name?") constituted tests of literalism (scored if response is "Yes" or "No," either verbally or nonverbally). Whereas Erickson claimed that 97% of his "deep trance" subjects and 90% of his "medium trance" subjects exhibited literal responses, we found that 87.5% of hypnotized, high-hypnotizable subjects' responses were nonliteral. Hypnotized and task-motivated subjects did not differ in their literal responding to the individual questions or when their scores were summed across questions. No support was secured for Erickson's assertion that literalism is a cardinal feature of hypnosis. PMID- 2270837 TI - Comment on "A factor analytic study of two scales measuring dissociation" by Fischer and Elnitsky. PMID- 2270838 TI - Hypnotic treatment of sleep-terror disorder. PMID- 2270839 TI - On the origin of the word "hypnotism". PMID- 2270840 TI - Magnetic resonance imaging: improved patient tolerance utilizing medical hypnosis. AB - Magnetic Resonance Imaging (MRI) is a medical diagnostic procedure which requires a patient to be placed supine into the cylindrical bore of a powerful magnet for approximately one hour. The patient's arms are usually against the sides of the magnet bore with a 3" to 10" space between the patient's face and the top of the magnet bore. This enclosure induces panic and claustrophobic responses in 1% to 10% of the patients undergoing the MRI procedure. There have been many failed diagnostic studies due to patient intolerance, and there are reports of procedure induced claustrophobia. We describe the hypnotic procedure utilized to reduce anxiety and panic for successful completion of MRI scans. Medical hypnosis has been an effective intervention in ten patients, permitting completion of their diagnostic procedure. PMID- 2270841 TI - Clinical applications of hypnosis in the physical medicine and rehabilitation setting: three case reports. AB - Hypnosis is useful in the rehabilitation setting to help patients master skills, to increase their sense of self-efficacy and self-esteem and, in general, to facilitate and accelerate their rehabilitation program. I used hypnosis with three patients where patient behaviors and beliefs were interfering with the rehabilitation treatment goals set by the patient and the health care team. Collectively, these cases demonstrate the use of hypnotic techniques in diagnosing and treating problems with patient compliance and assisting patients to gain greater benefit from their rehabilitation regimen. PMID- 2270842 TI - The effects of hypnosis on a parkinsonian tremor: case report with polygraph/EEG recordings. AB - Although Parkinsonian tremors typically disappear during sleep and are reduced during relaxation periods, the effects of hypnosis on this type of movement disorder have been generally ignored. We observed a patient's severe Parkinsonian tremor under hypnosis and monitored it with EEG and EMG studies. The patient was taught self-hypnosis and performed it three to four times daily in conjunction with taking medication. The results suggest that daily sessions of self-hypnosis can be a useful therapeutic adjunct in the treatment of Parkinsonian tremors. PMID- 2270843 TI - The use of hypnosis in a deaf patient with multiple personality disorder: a case report. AB - We present the first report of multiple personality disorder (MPD) in a prelingually deaf patient and the first description of alter personalities as the source of auditory hallucinations in a nonpsychotic deaf person. This young woman's history and clinical symptoms of MPD did not differ from those of hearing patients. A hypnotic trance was induced by instructing the patient in muscle relaxation, modeling relaxation with exhalation, and having the patient focus her gaze on the hypnotist repeatedly fingerspelling R-E-L-A-X. Hypnosis facilitated automatic handwriting, allowed the first meeting with an alter personality, and speeded the diagnostic process. Fingerspelling has not previously been reported in hypnosis of the deaf. It is a practical means of induction for a therapist who lacks fluent signing skills. It provides a narrow fix of gaze and avoids induction by physical stimulation, a process that some abused patients find upsetting. PMID- 2270844 TI - The pharmacological and pathological studies on Taiwan folk medicine (III): The effects of bupleurum kaoi and cultivated bupleurum falcatum var. komarowi. AB - The protective effects of water extract from roots of Bupleurum kaoi Liu, Chao et Chuang and Bupleurum flacatum L. var. Komarowi Koso-Polj on CCl4-induced hepatoxicity have been investigated. Both B. kaoi (p less than 0.05) and B. falcatum var. komarowi (p less than 0.01) possessed more marked anti-hepatotoxic pharmacological effects than Bupleurum chinense DC., the typical strain widely used in Taiwan. The pathological improvement from treatment by means of the three drugs to alleviate CCl4-induced hepatic toxicity was estimated using morphological changes of hepatocytes, reduction of inflammatory cells infiltration and liver function tests. PMID- 2270845 TI - The pharmacological and pathological studies on Taiwan folk medicine (IV): The effects of echinops grijisii and e. Latifolius. AB - The protective effect of "San-fang-feng" derived from the root of Echinops grijsii Hance on CCl4-induced hepatotoxicity has been studied. This crude drug was found to possess a marked hepatoprotective effect. A comparison of the protective effect with "Lou-lu" derived from the root of E. latifolius Tausch and "Pei-chai-hu" original Bupleurum chinense showed that E. grijisii and E. latifolius were more effective than B. chinense as reported previously. The results suggested that both E. grijisii and E. latifolius could correct the hepatocyte necrosis and functional disorder induced by the CCl4 treatment. PMID- 2270846 TI - Effects of single moxibustion on cutaneous blood vessel and microvascular permeability in mice. AB - The effects of a single cone moxibustion on cutaneous blood vessel and microvascular permeability in ddY mice have been studied by microscopical observation and by the dye leakage technique. In our results, moxibustion induced some kind of inflammatory response such as the blood vessel reaction with leukocytes exudation and the enhancement of microvascular permeability, which is considered one of the host defense mechanisms. PMID- 2270847 TI - Elementology of diabetes mellitus. PMID- 2270848 TI - Endothelin-1 levels are not influenced by tokishakuyakusan and keishibukuryogan treatment in women. AB - The effect of Tokishakuyakusan (TS) or Keishibukuryogan (KB) on endothelin-1 (ET 1), a newly identified peptide, in plasma and amniotic fluid from TS- or KB treated women or normal pregnant women following TS or KB treatment was studied during the menstrual cycle, gestation, delivery and the post-partum period. ET-1 levels during and/or after TS or KB treatment had no significant changes when compared with those in TS- or KB-untreated women. These results suggest that TS or KB has no effects on the ET-1 level during the menstrual cycle, gestation and the post-partum period. PMID- 2270850 TI - Hypotensive action of Salvia miltiorrhiza cell culture extract. AB - Salvia miltiorrhiza cell culture extract (SCE) was shown to produce dose dependent hypotensive response in normo-tensive rats. The mode of this hypotensive action was studied both in vivo and in vitro. This vasodepressor effect was not due to the presence of cations (potassium, calcium and magnesium) in the extract. In pharmacological antagonist studies, the hypotensive effect was shown not being mediated via the alpha-, beta-adrenoceptors, histamine receptors and autonomic ganglion; nor via direct vasodilation and diuresis. However, the vasodepressor effect was probably angiotensin- and/or bradykinin-related since captopril infusion potentiated the hypotensive effect of SCE. Furthermore, data indicated that the vasodepressor effect might be accounted for by the positive inotropic and negative chronotropic effects of SCE, the latter via its modulation of cholinergic activity. PMID- 2270849 TI - Effects of tokishakuyakusan and keishibukuryogan on steroidogenesis by rat preovulatory follicles in vivo. AB - The effect of Tokishakuyakusan (TS) and Keishibukuryogan (KB) on estradiol-17 beta, progesterone and testosterone in serum and ovarian tissue from PMS-treated immature rats was examined in vivo. The in vivo intravenous administration of 20 micrograms of TS or KB increased the concentrations of estradiol-17 beta, progesterone and testosterone. These results suggest that TS and KB stimulate in vivo the production of estradiol-17 beta, progesterone and testosterone by preovulatory follicles, and that TS stimulation is more effective than KB. PMID- 2270851 TI - Effects of a Japanese medicinal plant on the rat subtotal nephrectomy model: evaluation of its effect by microvascular casts. AB - Effects of a Japanese medicinal plant named Sairei-To, were examined in a rat experimental renal disease. Thirteen weeks after subtotal nephrectomy, the blood pressures in rats given Sairei-To (Sairei-To rats) were lower than those without Sairei-To. The urinary protein excretions and glomerular sclerosis were markedly decreased in the Sairei-To treated rats. Arteriolar diameters were measured using microvascular casts. The afferent and efferent arterioles were both significantly dilatated. The efferent arterioles in Sairei-To rats were dilated to a greater extent than that of the afferent. These results indicated that Sairei-To lessened renal damages in the rat subtotal nephrectomy model, possibly through the blood pressure reduction and the efferent arteriolar dilatation. PMID- 2270852 TI - The lack of antiplatelet effect of crude extracts from ganoderma lucidum on HIV positive hemophiliacs. AB - Effects of the extracts from Ganoderm lucidum (GL-P) to influence immune status of the hemophiliacs with positive HIV antibody and reversed helper/suppressor T lymphocyte ratio were studied. Since the extracts from G. lucidum have been reported to contain high levels of adenosine, the untoward antiplatelet effect of the extracts on hemophiliacs were highly concerned. Five patients of hemophilia A voluntarily received the extracts which has been analyzed to contain 150 mg of adenosine in 100 gm of the extracts. Patients were estimated to take 1.35 mg of the adenosine daily. Platelet aggregation tests before and after the trial of the extracts showed no significant change. Our crude extracts of the Ganoderma lucidum was considered not to have untoward antiplatelet effect in vivo despite the high contents of adenosine. PMID- 2270853 TI - A comparative study of Chinese cosmology cum-humorology with eight elements. AB - As agriculturist, man recognized Earth, Heat and Water as essential to plant life and projected them as cosmic elements. Pastoral man observed animals multiply due to reproduction. He realized that reproduction resulted from the union of opposites as male and female. Projecting reproduction, he conceived creation, which then resulted as the union of the cosmic pair of opposites. Heaven and Earth. The Chinese conceived of creation as starting with creative energy in its latent form, as Thai-Chi, meaning the absolute existence. Later, it assumed its dynamic form called Chhi. It was dual-natured with the opposites called Yang (light) and Yin (darkness). The reproductive power was projected as creative energy called Chhi and male and female opposites were projected as the universal pair of opposites as Yang and Yin. Creative energy produced the cosmic elements which in turn produced all creation. The cosmic elements of Chinese cosmology were Wood, Fire, Water, Earth and Metal. They also included the factors of humorology when the following elements had, as contents, items belonging to humorology, Wood-contained Air, Earth.....Moisture; Metal.......Dryness. By assigning dual-sense to three cosmic elements, Chinese humorology came into existence but has incorporated it in its cosmology. It is easy to equate Air = Vayu of Tridosha doctrine of India, Moisture = Kapha, Dryness = Pitta. Then with five elements of cosmology including three with dual-sense, as belonging to humorology, we have eight elements in all as cosmology-cum-humorology. It is obvious that Air, so important in the cosmologies of India and Greece, is no where explicit in Chinese cosmology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270855 TI - [The new therapeutic chimera. 5 years of cardiac transplantation in Madrid]. PMID- 2270854 TI - Changes in brainstem and cortical auditory potentials during Qi-Gong meditation. AB - "Qi Gong" (QG) is a meditation exercise known for thousands of years in China and has always been widely practiced. It has been claimed to have a variety of healing and other health benefits. To provide an understanding of the effect of QG on brain structures along the whole neural axis from the periphery to the cerebral cortex, we have monitored short-latency auditory brainstem evoked response, middle-latency response, and long-latency cortical auditory evoked potentials, before, during, and after QG. Our results showed that QG caused an enhancement of brainstem auditory evoked response with a concomitant depression of cortical responses. These observations may be related to the healing and other health benefits of QG. PMID- 2270856 TI - [Evolution of anthropologic concepts: from morphologic typology to genetic polymorphism]. PMID- 2270857 TI - [The exact location of diabetogenic and atherogenic fat]. PMID- 2270858 TI - [Diagnosis and subdiagnosis of depression]. PMID- 2270859 TI - [The dopaminergic signal in chromaffin cells]. PMID- 2270860 TI - [Evolution of the treatment of bleeding esophageal varices]. PMID- 2270861 TI - Europium chelate labels in time-resolved fluorescence immunoassays and DNA hybridization assays. PMID- 2270862 TI - Chemistry in the Capital. PMID- 2270863 TI - Use of ionomer membranes to enhance the selectivity of electrode-based biosensors in flow-injection analysis. AB - The use of ionomer membranes to enhance the selectivity of potentiometric enzyme electrodes in flow-injection measurement arrangements is examined. The ionomer membranes employed are permeable to analyte substrates but relatively impermeable to detectable ions that would normally interfere with the measurement of the substrates if the enzyme electrodes were in direct contact with the sample. As a model system, the selectivity of enzyme electrodes prepared with nonactin-based ammonium-sensitive polymeric membranes is evaluated. In the preferred configuration, a thin hydrophilic anion-exchange membrane is incorporated within a flow-through dialysis unit upstream from the enzyme-electrode detector. As the sample passes through the dialysis unit, neutral or anionic analyte molecules (urea or glutamine) move through the membrane while the permeation of endogenous ammonium ions and other cations in the sample is retarded. A flowing recipient buffer on the other side of the membrane carries the analyte substrate to the enzyme-electrode detector. Enhancements in selectivity for analyte substrates over endogenous ammonium and potassium ions are greater than or equal to 9-fold when compared to enzyme-electrode flow-injection analysis (FIA) systems assembled without the ionomer membrane unit. The analytical utility of the proposed system is demonstrated by the accurate measurements of urea in blood serum and L glutamine in hybridoma bioreactor media. PMID- 2270864 TI - Cyanide detection using a substrate-regenerating, peroxidase-based biosensor. AB - An enzyme-based, dual working electrode system is described for the sensing of cyanide. Horseradish peroxidase (HRP) is incorporated as the sensing element. A continuous monitoring of oxidative activity by the enzyme results through the generation and regeneration of substrates at the electrode surfaces. Thus, HRP is oxidized by hydrogen peroxide generated from dissolved oxygen, at the primary electrode, and then reduced through the secondary electrode by mediated electron transfer using ferrocene as a carrier. Ferrocene regeneration at this electrode is proportional to the intrinsic activity of HRP. The dynamics of the system are investigated by using a rotating ring-disk electrode. The enzyme is immobilized to provide better control over its catalytic activity and to increase the lifetime of the biosensor. Cyanide inhibition of current can be modeled by reversible binding kinetics. Detection of cyanide is possible in submicromolar (ppb) concentrations, with a half maximal response at 2 microM. The response time for detection of introduced cyanide is within 1 s. The sensor can be operated between 5 and 40 degrees C, and cyanide inhibition is unaffected by pH changes between 5 and 8. The sensor is reproducible for cyanide determination and is stable for over 6 months. PMID- 2270865 TI - Indirect inductively coupled plasma atomic emission determination of fluoride in water samples by flow injection solvent extraction. AB - An indirect determination of fluoride in water by inductively coupled plasma atomic emission spectrometry combined with flow injection coupled with solvent extraction is reported in this paper. A manifold for rapid determination of fluoride has been designed that uses a single coil for complex formation and extraction. The method involves the formation of lanthanum/alizarin complexone/fluoride complex and its extraction into hexanol containing N,N diethylaniline. The concentration of fluoride is determined indirectly by introduction of the organic layer into the plasma and measurement of the emission intensity of the La II 333.75-nm line. The optimum experimental conditions for the determination are described. A coiled groove phase separator fitted with a grid and PTFE porous membrane was used in this work. The sampling rate was 36 samples per hour and the calibration graphs were linear from 0.03 to 1.3 micrograms/mL. The relative standard deviation found was 2.16% for 200 microL of 1 microgram/mL of fluoride. The method is selective and has been applied satisfactorily to the determination of fluoride in water samples. PMID- 2270866 TI - Electrophoretic separations of proteins in capillaries with hydrolytically stable surface structures. AB - A procedure for obtaining highly stable coated capillaries for use in capillary electrophoresis (CE) is described. Reaction of surface-chlorinated fused silica capillaries with the Grignard reagent, vinyl magnesium bromide, followed by reaction of the vinyl group with acrylamide, results in an immobilized layer of polyacrylamide attached through hydrolytically stable Si-C bonds. This method is an extension of the capillary coating procedure described previously by Hjerten, differing in the means by which the polyacrylamide layer is bonded to the capillary walls. Capillaries treated in the manner described here can be used over a pH range of 2-10.5, without noticeable decomposition of the coating. In comparison to uncoated capillaries, separations of proteins using such coated capillaries are improved due to a reduction in protein adsorption to the capillary walls, although interaction is still present to some degree as evidenced by an inability to obtain plate counts as high as those predicted by theory. Electroosmotic flow is virtually eliminated in the coated capillaries, resulting in improved reproducibilities of protein migration times in comparison to uncoated capillaries. Additionally, peak skew is evaluated for model proteins and improvements are noted for the coated capillaries. Results are presented for separations of model protein mixtures, comparing the performance of the vinyl bound polyacrylamide coated capillaries and uncoated capillaries at both high and low pH extremes. PMID- 2270867 TI - Determination of nucleotides in fish tissues using capillary electrophoresis. AB - Capillary electrophoresis has been applied to quantitate nucleotide degradation in fish tissues, to provide a basis for determining the K value, an indicator of fish freshness. The three major compounds, inosine monophosphate (IMP), inosine (HxR), and hypoxanthine (Hx) were distinctively separated at 416 V/cm applied potential, 100 mM CAPS buffer, pH 11. There was a good correlation between the peak area and the nucleotide concentration. By using a short distance (22 cm) from the sample entrance to the detector, the identification and determination of these compounds in each sample were completed within 15 min. The results obtained correlated very well with those obtained by enzymatic assays. The capillary was completely regenerated with 1 N NaOH, to dissociate all bound materials from the capillary wall, mainly cations in the fish extract. This provided the same silica surface for repeated runs, resulting in reproducible electropherograms. PMID- 2270868 TI - Comparison of mass spectral techniques using organic peroxides related to artemisinin. AB - The mass spectra of three peroxides related to artemisinin (1) are compared in nine different ionization modes. Ion trap mass spectrometry (MS/MS) spectra reveal numerous pathways for the electron impact (EI) decompositions. In the EI mode, the best spectra are obtained by using the ion trap mass spectrometer at low temperatures. Loss of oxygen is observed with the other EI spectrometers, suggesting catalytic decomposition in the ion source. Methane positive and negative chemical ionization (CI) spectra show considerable fragmentation, while isobutane CI spectra show only (M + H)+ for 1 and (M + H - H2O)+ for dihydroartemisinin (2) and (3). An unusually abundant (2M + H)+ is observed for 1 in both positive-ion plasma desorption and fast atom bombardment mass spectra. PMID- 2270869 TI - Laser-enhanced ionization spectroscopy in an extended inductively coupled plasma. PMID- 2270870 TI - Selective detection of carbon-13-labeled compounds by gas chromatography/emission spectroscopy. PMID- 2270871 TI - Multi-enzyme electrodes for the determination of starch by flow injection. AB - A tri-enzyme electrode has been developed for determining starch in a flowing stream based on amperometric monitoring of hydrogen peroxide at a potential of +600 mV versus a silver--silver chloride reference electrode. The nylon-based starch-sensing membranes (over a platinum electrode) were prepared from an enzyme cocktail containing various ratios of amyloglucosidase (AMG), mutarotase (MUT) and glucose oxidase (GO). The best starch-sensing membrane (to give the type A electrode) was made from an enzyme cocktail of AMG--MUT--GO (2000 + 100 + 100 U; where 1 U = 16.67 nanokatals), i.e., containing a high level of AMG. In this system, starch samples were first incubated with soluble alpha-amylase (alpha AMY) (1000 U) for 1 h at room temperature prior to analysis with the tri-enzyme electrode. Attempts were also made to immobilize alpha-AMY on to nylon net, either alone or as a component of a four-membrane starch-enzyme electrode but starch signals were weak compared with those generated by starch pre-treated with soluble alpha-AMY. This system, associated with the type A starch electrode, not only exhibited a calibration of wide linear range (1 x 10(-4)-0.1% m/v starch) but also showed promising operational properties. It has excellent thermal stability over the range 30-70 degrees C. PMID- 2270872 TI - Determination of L-ascorbic acid in fruit and vegetable juices by flow injection with immobilised ascorbate oxidase. AB - Ascorbate oxidase was immobilised on cyanogen bromide activated-Sepharose 4B and incorporated in a flow-injection system with amperometric detection at a glassy carbon electrode at +0.6 V. On passage through the immobilised ascorbate oxidase a fraction of the L-ascorbic acid was converted into dehydroascorbic acid and the decrease in signal was measured. This could be directly related to the amount of L-ascorbic acid present. The calibration graph was linear over the range 0-400 ng ml(-1) with a correlation coefficient of 0.9994. The detection limit (2 sigma) in phosphate buffer (0.08 M, pH 5.5) was 4.0 ng ml(-1). The relative standard deviation for a 200 ng ml(-1) standard was 1.0% (n = 10) and the sampling throughput was 30 samples h(-1). The method was used for the simple and rapid determination of L-ascorbic acid in fruit and vegetable juice. PMID- 2270873 TI - Fourier transform Raman spectroscopy in the analysis of polypeptides . PMID- 2270874 TI - Determination of trace amount of cobalt in feed grains and forages by solvent extraction and graphite furnace atomic absorption spectrometry. AB - A method is described for the determination of trace amounts of cobalt in feed grains and forages with a detection limit of 1 ng g-1. Samples are ashed in a muffle furnace and complexed with 2-nitroso-1-naphthol. Following solvent extraction, cobalt is determined using graphite furnace atomic absorption spectrometry. The assay can be carried out in a normal analytical laboratory without the need for special "clean" rooms. Reagents have been selected to keep reagent blank values at low levels, and heptan-2-one is used as extracting solvent to avoid problems with evaporation. The assay has been used for diagnostic purposes and to formulate special low cobalt diets for sheep for experimental purposes. PMID- 2270875 TI - Simultaneous determination of some active ingredients in cough-cold syrups by gas liquid chromatography. AB - A simple, efficient and accurate gas-liquid chromatography (GLC) method for the simultaneous determination of eight active ingredients in cough-cold syrups has been developed. The active ingredients under study were bromhexine, chlorpheniramine, codeine, dextromethorphan, diphenhydramine, ephedrine/pseudoephedrine, guaiphenesin and papaverine. Before injection, the active ingredients were first separated, from the excipients present in the cough cold syrups, with chloroform, from alkaline medium. They were then separated by GLC on a glass column (5 ft x 2 mm i.d.) packed with 3% of OV-25 supported on Supelcoport (80-100 mesh). The column temperature was maintained at 170 degrees C for 1 min, then programmed to 265 degrees C at a rate of 10 degrees C min-1, and maintained at this temperature for 10 and 1 min, respectively, for samples with and without papaverine. The flow-rate of the nitrogen carrier gas was 30 ml min 1. A flame-ionisation detector was used for detection, and clomipramine hydrochloride was used as the internal standard. The recoveries of the drugs ranged from 96.0 to 99.7%, and the relative standard deviations for ten replicate determinations ranged from 0.49 to 4.7%. Results are reported for nine commercially available cough-cold syrups. PMID- 2270876 TI - Spectrophotometric determination of cysteine and cystine in urine. AB - A spectrophotometric method for the determination of cysteine and cystine in urine is described. This method is a modification of that reported for the determination of cysteine and cystine in proteins. The determination in urine is specific and simple. The colour develops at room temperature and no pre-treatment of urine is needed. Other amino acids, urea, uric acid, ascorbic acid, bilirubin, biliverdin, carbohydrates, hormones, acetone, salicylic acid, small amounts of protein and other common components of urine do not interfere. The method is particularly suitable for the diagnosis of hepatic cystinuria and other diseases characterised by high sulphur-containing amino acids in urine. PMID- 2270877 TI - Spectrophotometric determination of acetone using vanillin. AB - A sensitive method is described for the spectrophotometric determination of acetone in water. Acetone reacts with vanillin in alkaline medium forming a yellow-orange dye with an absorption maximum at 430 nm. Beer's law is obeyed in the range from 0.5 to 5 p.p.m. of acetone in water. Molar absorptivity and Sandell's sensitivity were found to be 11.0 x 10(3) +/- 100 l mol-1 cm-1 and 0.005 micrograms cm-2, respectively. The important parameters for complete colour development were optimised and the method was used for the determination of acetone in biological samples. The method was also applied successfully to the determination of acetone in air after absorption in sodium hydrogen sulphite solution. PMID- 2270878 TI - Preferential distribution of streptomycin in pig kidney cortex. AB - In 14 pig kidneys containing streptomycin, an average distribution ratio of 2.5:1 was found for the streptomycin between the cortex and medulla. It is suggested here that cortex alone be used, instead of mixed kidney tissue, in regulatory meat monitoring schemes. PMID- 2270879 TI - [Physiopathology of the esophagogastric junction]. PMID- 2270880 TI - [Segmental osteotomies of the mandible in the orthodontic surgical treatment of malformations of the facial bones]. AB - In this article the Authors take under consideration surgical techniques of segmental osteotomy of the mandible in the treatment of the maxillo-facial skeleton alterations. The anterior inferior alveolar segmental osteotomy, total subapical osteotomy, anterior subapical osteotomy, genioplasty and the midline mandibular osteotomy are presented with their surgical techniques and indications. Therefore the authors present two cases of patients undergone to orthodontic--surgical treatment. PMID- 2270881 TI - [Occult carcinoma of the thyroid gland: an epidemiological study of autopsy material]. AB - The occurrence of occult thyroid carcinoma at autopsy was examined in 507 consecutive autopsies performed over one-year in subjects without clinical evidence of thyroid cancer, from different regions of Italy, including areas of endemic goiter. We found 54 (10.65%) occult thyroid carcinomas. In 37 cases the histologic pattern was of the papillary type, with diameter ranging between 176 and 6000 microns, 12 of these cases showed a typical papillary pattern, 6 had a marked fibrosis, 2 had a cystic pattern, one showed a lymphoid stroma, and 17 had a follicular pattern. The remaining 17 cases were medullary carcinomas, with a diameter ranging from 50 to 1600 microns. The percentage of occult thyroid carcinomas reported in the present study may constitute real value of the occurrence of this tumor in the Italian population. PMID- 2270882 TI - [Benign tumors of the stomach of neurogenic origin]. AB - The benign tumours of the stomach are statistically 1-4% of gastric tumours. Progress in diagnostic is in relation with new immuno-histochemical methods and modern radiologic and endoscopic studies. The histopathologic findings are very important for differential diagnosis with benign gastric tumours of mesenchymal origin, specially leiomyomas. Areas of malignant degeneration are sometimes localized in benign gastric tumours of nervous origin. Only in these situations is necessary mayor radical surgery, as gastro-duodenal resection or a total gastrectomy. The authors, in a personal case series of 30 benign gastric tumours, illustrated 5 cases of benign tumours of nervous origin of the stomach. The histologic findings of these cases, all treated with surgical excision, are: one malignant neurinoma, two neurofibromas and two benign schwannomas. In the case of malignant neurinoma has been necessary reinterventions for recurrence. In spite of surgical and chemotherapeutic treatment the patient died for abdominal and hepatic metastasis. PMID- 2270883 TI - [Gastric polyps: role of endoscopy]. AB - Elster's classification differentiates epithelial gastric polyps on the basis of cells origin and relative tendency to change into a malignancy. Out of 3.920 endoscopy of upper digestive tract during the last 10 years, we found 41 gastric polyps, 50% asymptomatic. Endoscopic polypectomy were performed in 61% of cases, without any complication. The other 39% were followed-up and/or surgically resected, according to the results of biopsy. Endoscopy is mandatory for detection of lesions often asymptomatic and histological study of surrounding gastric mucosa. Small polyps must be treated by radical endoscopic polypectomy. If they are too big for endoscopic polypectomy, it's well advised and safer to perform periodic biopsy for hyperplastic type and a surgical resection for adenomatous ones. The detection of intestinal metaplastic or malignant changes beyond basal membrane suggests a resection both subtotal or total according to topography of the lesions. In conclusion the role of endoscopy is well defined in order to clarify histological attributes of gastric epithelial polyps and surrounding mucosal areas. More restricted is its role in the treatment of these lesions. PMID- 2270884 TI - [A point about obstructive non-neoplastic pathology of the duodeno-biliary pancreatic junction]. AB - Various benign pathological conditions of Oddi's sphincter may give origin to clinical manifestations due to hindrances to biliary flow into the duodenum; the hypertonic dyskinesia, proper, odditis and fibrosclerotic dystrophies. Such forms develop very big problems from a diagnostic and therapeutical point of view, even if an adequate therapy permits in most cases to reach definite results. Therapy in inflammatory forms (odditis) must be first of all of medical type; only when these are changing into fibrosclerotic forms or are manifest in an acute way it is meet to proceed surgically on the sphincter. The action on the sphincter, either by means of endoscopy or surgery, is performed with caution in the forms of hypertonic dyskinesia (only when such forms are going on and have had a long duration, or even resistant to any pharmacological therapy) because of the high percentage of painful recurrences. The cutting of Oddi's sphincter is on the contrary the first therapeutical choice in the fibrosclerotic forms, with immediate success on the symptoms and the results in the long run are optimal. PMID- 2270885 TI - [Ogilvie's syndrome]. AB - Ogilvie's Syndrome is defined as acute distension of the colon without any mechanical obstruction. We reported two new cases who underwent surgical treatment and the revision of the literature. Four hundred eight-six cases are described until now. The physiopathology is unknown. The diagnosis is done with abdominal x-ray, barium enema must be used with attention. The more frequent symptoms are nausea, vomiting, diarrhea, and abdominal pain. The perforation of the colon is possible with a diameter of 9-12 cm. The mortality was 11.3% in two hundred ninety patients (59.6%) who underwent conservative treatment. In one hundred ninety-six patients who underwent surgical treatment the mortality was 28.5%. The treatment is conservative, medical or endoscopic. The best surgical treatment is the tube cecostomy. PMID- 2270886 TI - [Hartmann's procedure in emergency surgery of the colorectum]. AB - The authors report their experience with Hartmann procedure. 28 patients were treated: 21 males and 7 females. The mean age was 58 years. Perforative diverticulitis was the commonest indication (14 patients), followed by carcinoma (11 patients). Miscellaneous causes accounted for 3 patients. This procedure was primarily performed as an emergency operation (71%). One patient died post operatively (3.5%); post-operative morbidity was 10.7%. A second operation was not planned if the first operation had been performed for palliation of metastatic or locally advanced cancer (7 patients). Restoration of colonic continuity was achieved successfully in 14 patients with no mortality and morbidity. According to their experience, authors believe Hartmann procedure to be the most suitable operation facing a left colon emergency. It is usually easy to perform and well tolerated by poor risk patients. PMID- 2270887 TI - [Aneurysm of the popliteal artery: diagnostic and therapeutic considerations]. AB - The authors settle the roles of the most recent diagnostic methodologies useful to frame the popliteal aneurysm pathology namely digital arteriography, N.M.R., and doppler-flowmetry. They emphasize, in an observed case, the adopted therapeutic criteria, that is basically interventional. The thinness of saphenous veins draws toward the employing of "Goretex". PMID- 2270888 TI - [Voluntary ingestion of packages containing narcotic drugs. Diagnosis and treatment in a clinical case]. AB - A case of intracorporeal concealment of narcotics is reported. Cocaine mixed with marihuana were the ingested drugs. Surgical treatment is, in selected cases, the safest method to remove such packages from the gastrointestinal tract also in subjects without mechanical obstruction. In fact, rupture of a packet threatens the patient's life, because of cocaine's high toxicity and lack of antidote. PMID- 2270889 TI - [Peritoneal oxygenation-dialysis as a temporary treatment of intestinal infarction]. AB - The interval preceding the growth of irreversible lesions in an abdominal apoplexy is variable (3-48 hours). It may be used to improve the ischaemic viscus oxygenation, also compensating possible metabolic imbalances. 16 rabbits were used for research, in which apoplexy by the ligature of the arteria mesenterica superior was induced. Dialysis-oxygenation peritoneal treatment was carried out for 8 rabbits, the results of which were evaluated on the basis of the intestine macroscopic morphologic aspect; on the basis of the hematic phosphates values and in enteral biopsy. The oxygenation-dialysis produced a rapid improvement in enteral hue and in enteral motility, an important increase of PO2 and a reduction of hematic phosphates compared with the control group. Histologic examination did not show any significant variation. The attempt to increase general oxygenation by supplying PO2 via the peritoneum, was partly successful (10-15%). The aim of oxygenation the ischaemic enteral zone was successful. This due to elimination of CO2 and toxic products using dialysis. This simple method seems to be effective but further tests on swine would be necessary for clinical applications. PMID- 2270891 TI - [Limitations and dangers of x-ray computed tomography in the assessment of inoperable bronchial carcinoma]. PMID- 2270890 TI - [Antibiotic prophylaxis of infectious complications of cervico-facial surgery]. AB - Head and neck surgery presents a high operating risk of infectious complications. We agree upon the fact that 60% of the so-called infected operations would be complicated by secondary infections if they are not treated by antibiotic therapy. Such a premise justifies the more and more used application of a chemoprophylaxis in surgery, carried out preoperatively. The AA. report 81 cases of patients, from 15 o 70 years old (62 males, 19 females), subjected to head and neck surgery and subdivided into two groups according to the kind of the operation. I group: 40 patients subjected to operations of minor infectious risk, the whole number subjected only to the prophylactic pre-operational treatment with 1 gr. of Ceftriaxone by intravenous injection, 30-60 min. before the operation. II group: 41 patients subjected to infected operations: 21 patients treated with 1 gr. of Ceftriaxone by intravenous injection, 30-60 min. before the operation, and 20 patients treated with Cefazolin, 1 gr. per daily administration, carried out after the surgical operation. As dealing with infected operations of high risk infectious complications, the antibiotic treatment has been carried out for 7-8 days for all the patients. In operations with minor infectious risk (group I) we have had a good post-operational course, without any infectious complication; the use of Ceftriaxone, with only one preoperational dose, is extremely useful for this group of patients. In infected operations of head and neck oncological surgery (group II) the cases of infectious complications have been 2 in the subgroup treated with Ceftriaxone, and 4 in the subgroup treated with Cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270892 TI - [Viability of new valvular homografts. An evaluation at the Henri Mondor Hospital]. AB - The renewed interest in valvular homograft is due to the new concept of their viability. This viability requires procurement from organ donors and preparation in rich tissue culture medium immediately prior to cryopreservation. This viability, confirmed by morphological tests especially electron microscopy, and by cell culture tests is the basis for satisfactory long-term results. Antigenic aspects justify rigorous respect of A-B-O compatibility. A preliminary clinical series of 35 valvular homografts (16 on the right side and 19 in the aortic position), implanted especially in children over the last five years at the Henri Mondor Hospital, is reported here, No tissue failures have been reported to date. PMID- 2270893 TI - [Coronary artery bypass using bovine internal mammary artery]. AB - Among 760 patients who underwent coronary artery bypass graft (CABG) 8 received one or two bovine internal mammary artery grafts. The surgical procedures were 4, 3 and 3 CABG respectively in 1, 3 and 4 cases with greater saphenous veins in 4 cases, internal mammary artery in 4 cases and bovine internal mammary artery in 11 cases. The 3 mm bioflow grafts were used to revascularize the left coronary artery in 6 cases (to the left anterior descending, circumflex artery) and the right coronary artery in 5 cases. The indications for the use of bovine mammary artery grafts were lack of suitable autologous vessels because of bilateral saphenous vein stripping in 4 cases, bilateral varicose veins in 3 cases and inadequate length of vein in 1 case. Post-operative angiographic studies of these bovine mammary grafts with a maximum follow-up of 11 months showed 5 occluded grafts, 2 grafts with proximal stenosis, one graft which remained patent until the patient died and 3 grafts still under evaluation. Bovine internal mammary artery grafts provide a solution for the acute stage of coronary disease, but do not achieve total and durable revascularization. Their use must remain exceptional. PMID- 2270894 TI - [Cardiac hydatidosis. Review of recent literature and report of 15 cases]. AB - In the context of a personal series of fifteen cases of hydatid cyst of the heart, the authors present a computerized review of the last one hundred cases published in the literature. The modern features of the disease are discussed together with its severity (mortality of 23.47% in 98 recent cases). Despite the considerable contribution of ultrasonography, computed tomography and magnetic resonance imaging, a certain number of pejorative criteria appear to persist:delayed diagnosis, diagnostic error, acute pulmonary oedema and incomplete surgical cure. PMID- 2270895 TI - [Protection and reperfusion of the myocardium by cardioplegia with blood enriched in aspartate and glutamate. Technique and initial results. Report of 60 cases]. AB - From 1st November 1987 to 30th September 1988, 27 patients with recent myocardial infarction and 33 patients at high risk of postoperative circulatory failure were operated according to the same protocol. In each case, myocardial protection, at the time of aortic clamping, consisted of an intra-coronary injection of a cardioplegic solution of blood enriched with aspartate and glutamate, administered in 3 phases (normothermic induction, hypothermic induction, normothermic reperfusion) according to the protocol described by Buckberg et al. The operative mortality was 11.6% (7/60) and 46.6% (28/60) of patients did not develop any postoperative complications. It is difficult to draw any conclusions concerning the superiority of the method on the basis of a non-comparative clinical study, but its simple application and its safety appear to be clearly demonstrated. PMID- 2270896 TI - [Repair of Tetralogy of Fallot with a single pulmonary artery. Developmental modalities]. PMID- 2270897 TI - [Postoperative intensive care after thymectomy for myasthenia gravis]. AB - The post-operative management of the myasthenic patient after thymectomy through sternotomy has changed in the last decades. After years of routine preoperative tracheostomies followed by routine prolonged intubation nowadays it is possible to wean the patients from the ventilation and to extubate them early after surgery while reintroducing the acetylcholinesterase inhibitors therapy. A series of 15 patients operated on between 1985 and 1988 for removal of thymic rests or thymoma is presented and confirms this evolution. The clinical and gazometric criteria allowing an early weaning from the ventilator are analyzed. However certain patients with the most severe forms of myasthenic still need prolonged ventilatory support. PMID- 2270898 TI - [Development of 62 typical carcinoid tumor of the bronchi surgically treated. Prognostic value of histopathological features]. AB - The pathological and clinical features of 62 carcinoid tumours of the bronchus operated between 1975 and 1987 were reviewed in order to determine the prognostic value of certain parameters: limit of proliferation, vascular invasion, lymph node involvement. This series corresponded to 36 central tumours and 25 peripheral tumours, all treated surgically. One patient was lost to follow-up, 3 developed recurrences, 56 are still alive without recurrence and 3 died from intercurrent causes. The histological appearance of the tumours was homogeneous and typical. Twenty-eight lesions were strictly intrabronchial, 34 invaded the lung with incomplete limits in twenty cases. The tumour showed signs of vascular invasion in ten cases and the adjacent lymph nodes were invaded in eight cases. The local recurrence was undoubtedly related to an excessively conservative primary resection, as the primary tumour did not demonstrate any unusual features. The two tumours which metastasized showed vascular invasion: one metastasized to a hilar node, but these features were observed in other cases which retained a benign course. The standard histological diagnosis of typical carcinoid tumour does not appear to raise any particular difficulties; it is reliable. The course of the disease is sometimes malignant but no histological parameter is able to accurately predict this outcome. PMID- 2270899 TI - [Esophago-bronchial fistula in adults]. AB - The authors report five cases of benign oesophago-bronchial fistula in adults. These chronic bronchitic patients presented with recurrent episodes of secondary lung infections (or even haemoptysis). Questioning of the patients revealed a history of coughing when swallowing liquids in three cases. Two women concealed this symptom, which was only revealed retrospectively. The fistula was detected by upper GI series in three cases and by oesophageal fibroscopy in one case. In the remaining case, it was discovered at operating for severe haemoptysis. In four of the five cases, the fistula was situated on the right and was of post tuberculous origin. In one case of post-traumatic fistula, it involved the left main bronchus. All of the patients were operated: a resection-suture of the fistula was performed via the oesophageal approach and, via the bronchial approach, simple suture of the fistula was possible in two cases, while resection of the destroyed pulmonary parenchyma was necessary in three cases (one right lower lobectomy, two bilobectomies). Demonstration of the oesophago-bronchial fistula, definition of its site and assessment of the condition of the pulmonary parenchyma are essential steps to be performed prior to surgery. PMID- 2270900 TI - [A superior vena cava syndrome of unusual etiology: compression syndrome of the innominate veins]. AB - A 65-year-old hypertensive and atheromatous presented with "unilateral superior vena cava syndrome". Venography and computed tomography scan with hemodynamic studies demonstrated an intermittent compression of the left innominate vein by the supra-aortic trunks, mainly due to the left subclavian artery, during expiration. The late development of symptoms might be due to arterial atheroma coupled with a narrow superior mediastinum. The case described here is a thoracic equivalent of Cockett's syndrome and so can be called "innominate vein compression syndrome". PMID- 2270901 TI - [Giant cystic lymphangioma of the mediastinum]. PMID- 2270902 TI - [Contribution of x-ray computed tomography and MRI to the surgical diagnosis of bronchial cancers. Comparative evaluation of x-ray computed tomography, MRI and thoracotomy in 111 cases]. AB - Computed tomography and magnetic resonance imaging have respectively decreased the incidence of exploratory thoracotomy by 11.6% to 5.7% then 5.3% after their successive inclusion in the assessment of the operability of lung cancers. Based on a systematic comparison of CT and MRI with exploratory thoracotomy in 111 patients, the yield, sensitivity and positive predictive value of these examinations was assessed in relation to tumour extension to various sites: to the chest wall, for which the sensitivity was poor (38% for CT, 54% for MRI) with a moderate predictive value (71% for CT, 77% for MRI); to the mediastinum with improved sensitivity (69% and 72%) but an uncertain predictive value (61% and 72%). The sensitivity and predictive value were then measured for lymph node involvement: N1: moderate sensitivity (69% and 76%) but a good predictive value (95% and 92%); N2 and N3: good sensitivity (79% and 93%) but a poor predictive value (70% and 66%). Apart from a few particular indications specific to MRI, especially in the apex, left hilum and in contact with the atrium, the efficacy of these two investigations is very similar. However, their lack of specificity means that certain exploratory thoracotomies are still justified in order to assess the operability of the tumour. A surgical or mediastinoscopic anatomical assessment is still necessary for a good classification of lymph node extension of lung tumours. PMID- 2270903 TI - [Value of superior angiocardiography in the evaluation of the surgical excision of bronchial cancer. Respective role compared to thoracic x-ray computed tomography]. AB - The place of angiography-superior vena cavography in the assessment of the resectability of a lung cancer must be defined in comparison with the data provided by thoracic computed tomography. Sixty-six patients with proximal lung cancers of doubtful resectability were studied by means of angiography and computed tomography and the results of these preoperative investigations were correlated with the operative findings. The sensitivity of these two examinations for the diagnosis of vascular invasion preventing pulmonary resection is poor (53% and 47% respectively). The specificity and positive predictive value of angiography appear to be slightly superior to those of computed tomography (Sp: 96% and 82%, PPV: 78% and 47%, respectively). The diagnostic performance of these two examinations remains poor. Magnetic resonance imaging may replace these two examinations in the future. PMID- 2270904 TI - [Perfusion scintigraphy and surgical excision of bronchial cancers]. AB - In a series of 1,800 operated lung cancers, 93 had a unilateral perfusion scan less than or equal to 20% (36 perfusions = 0, 15 between one and 10% and 42 between 11 and 20%). Major amputations were more frequent on the left side and constituted a pejorative but non-decisive factor for surgical nonintervention although was not synonymous with inoperability. The extent of the resection increased with the severity of the amputation. PMID- 2270905 TI - [Justifications and benefits of exploratory thoracotomy in stage IIIb bronchopulmonary cancer]. AB - From January 1980 to December 1984, 270 patients underwent exploratory surgery for Non Small Cell Lung Cancer with or without peritumoral lymph node involvement. In group 1: for 167 patients (62%) unresectable cancer was found. In group 2: for 103 patients (38%) an extensive resection was feasible. This study allows comparison of these two groups and confirms the value of exploratory thoracotomy. The resection was extended to the superior vena cava in 12% of cases, the trachea and carina in 28.15% and the left atrium in 49.50%. Survival in group 1 was similar to that of non operated patients (i.e. less than 10% at one year) and the mortality was 1.2% with no operative mortality. Survival of group 2 was considerably better: 58% at 1 year, 26% at 3 years, 23% at 5 years. The mortality was 3.9% with no operative mortality. Three year survival of patients with T4 N0 was clearly higher than that of T4 N2 (38% versus 17%). Although the results were poor for patients with N3 disease and those who underwent incomplete resections, they were nonetheless better than in those patients with unresectable tumors (16% versus 9% at 18 months). We conclude that: exploratory thoracotomy is safe, a significant number of patients (38% in our series) may benefit from this approach, and that it is sometimes hazardous to contra-indicate surgery for patients suffering from lung cancer only on the basis of X-Ray findings. PMID- 2270906 TI - [Outcome of 100 necessary exploratory thoracotomies for bronchial cancer]. AB - The outcome of one hundred exploratory thoracotomies for lung cancer (9.1% of operations) was studied. There were 4 postoperative deaths. After the operation, 6 patients did not receive any further treatment, 62 received radiotherapy, 25 received a combination of radiotherapy and chemotherapy and 3 received chemotherapy. The disease-free interval was very short with development of metastases (55 cases) and local recurrences (29 cases). The survival was also short: less than 10% at 2 years; it was significantly poorer than that observed in a group of non-operated patients with an equivalent stage of lung cancer. These findings suggest the need for stricter evaluation of operative indications. PMID- 2270907 TI - [Repair of chest wall defects after full thickness surgical resection]. AB - The authors discuss the development of their approach to the repair of full thickness chest wall resection based on a series of twenty-two patients operated between 1967 and 1989. The defect resulting from resection of all tissue planes, either for breast in situ, recurrences, radiation lesions or primary tumours, raises difficult problems. Mammary or cutaneous autoplasties, performed during the early years, have become less frequent, essentially because of the development of musculo-cutaneous flaps (pectoralis major, rectus abdominis, latissimus dorsi) which provide global anatomical and functional repair. The greater omentum island flap, used since 1974, still occupies an important place because of its plastic and trophic qualities in irradiated regions. When chest wall rigidity is compromised, Mersilene patch remains the material of choice. The quality of the results obtained in terms of comfort justifies the use of this major surgery which is now well defined. PMID- 2270908 TI - [Treatment of pulmonary arteriovenous aneurysms by vaso-occlusion. Technique and results after a year]. AB - Forty two pulmonary arteriovenous malformations (PAVM) in seventeen patients were treated by coil vaso-occlusion between 1979 and 1989. The techniques of deposition of coils and spiders and the precautions taken to avoid complications are described. Complete occlusion of the arterial pedicles of the PAVM was immediately obtained in 34/37 pedicles. 3/37 were occluded secondarily. Five PAVM were submitted to surgery demonstrating the reciprocal indications for surgical and per-angiographic techniques. Except in one patient, in the beginning of our experience, the observed complications were minor and we have subsequently modified our techniques to avoid them. PMID- 2270909 TI - [Hypoglycemic pleural mesothelioma. A case report]. AB - Organic hypoglycemia occurs in pancreatic and mesenchymal tumors. Thirty percent of extrapancreatic tumors are intrathoracic. A patient with hypoglycemic pleural mesothelioma was treated by surgical excision without recurrence five years after surgery. The mechanisms of hypoglycemia are not clearly established. The recurrence of hypoglycemia is a good sign of tumor recurrence. PMID- 2270910 TI - [Extracorporeal lithotripsy for cholelithiasis: state of the art in 1990]. PMID- 2270911 TI - [Repercussions of surgery effecting tumor growth]. PMID- 2270912 TI - [Proposal for a polyvalent Simplified Acute Physiology Score of severity in biliary tract surgery]. AB - The SAPS score proposed by Le Gall, was used in 128 patients undergoing biliary surgery between January 1987 and April 1988. The score is based on the laboratory data for the first day. The cumulative post-operative complication rate was established during hospital stay and at one month after discharge. There is a highly significant correlation between the SAPS score, the morbidity and the mean hospital stay. From this study it seems valuable to use this score in surgery reports. PMID- 2270913 TI - [Superficial gastric cancer. Report of a series of 57 cases]. AB - We have studied a total of 395 patients with gastric cancer during the past 16 years 57 of whom presented with superficial gastric cancer. The most frequent symptom was gastric pain in 47 patients. Barium weal was not helpful in the diagnosis and failed to define the nature of this disease in 43 patients. Endoscopy enabled visualization of an abnormality in 55 patients, the lesion seen was considered to be compatible with a diagnosis of superficial gastric cancer in 42 cases. The combined results of endoscopy and biopsy diagnosed malignancy in all cases, but a sufficient number of endoscopic biopsy specimens must be taken (5 to 7). Cases of superficial gastric cancer had an 24% incidence of other non gastric malignancies in our series. All patients were treated by surgical resection. The tumor was confined to the mucosa in 38 patients and had infiltrated the submucosa in 19 patients. Four patients had lymph node metastases. The five year actuarial survival was 75% for all the patients and 85% when the lesion was confined to the mucosa. In contrast, the five year survival for the 283 patients with resected gastric cancer was only 23%. Although the prognosis of superficial gastric cancer is remarkably good, patients should be carefully followed over a long period for late recurrent (one patient in our series) of the primary cancer and possible metachronous cancer of other organs. PMID- 2270914 TI - [Difference in the action of prostaglandin E2 (PGE2) on longitudinal circular muscle contractions of the colon. Experimental study in dogs]. AB - The effect of prostaglandin E2 (PgE2) on the circular and longitudinal contractions of the canine colon was studied in chronic conditions. A mechanical transducer developed in our laboratory and implanted on the canine colon collected simultaneously and separately the variations of length in two perpendicular directions. The recordings started at the 6 postoperative day. The colonic motility was recorded two hours before (as control period) and two hours after the intravenous injection of PgE2 at three different doses: 0.1-1.0 and 10 micrograms/kg. PgE2, at the three doses, induced, progressively over time, a significant decrease in duration and amplitude of the circular contractions, while the amplitude of longitudinal contractions remained unchanged. 10 micrograms/kg of PgE2 immediately induced a significant increase in the duration of longitudinal contractions followed by a decrease in this value during the 2nd hour after PgE2 administration. Each dose of PgE2 shortened the period of recurrence of longitudinal contractions, inducing rapid or immediate bursts of contractions. This effect was moderate or absent for the circular contractions. It is concluded, that PgE2 has different actions on circular and longitudinal contractions of the colon. According to the dose used, it induces hypokinesia (relaxation) in the circular muscle and premature strong contractions in the longitudinal motor activity. PMID- 2270915 TI - [Is visceral surgery justified in patients over 90 years of age?]. AB - The objective of this study was to evaluate the results of visceral surgery in patients over the age of 90 years by defining the indications, prognostic factors and short-term and intermediate results. This study was based on 50 patients operated between 1983 and 1987, consisting of 46 women and 4 men with a mean age of 92 years and a range of 90 to 98 years. 74% of the patients lived in long-stay hospitals, 26% lived at home, 28% were autonomous, 30% were semi-autonomous and 42% were bed-ridden. The majority of the patients were classified as ASA III. The mean number of visceral lesions was 3. 20% suffered from a malignant disease and 80% from a benign disease. 60% underwent emergency surgery and 40% underwent elective surgery. Postoperative complications were observed in 48% of cases, 58% of which had a fatal outcome. Sixteen patients (32%) died during the first postoperative month. The factors with a significant influence on mortality were: emergency in institutionalized patients (p less than 0.05), the ASA classification (ASA III and more, p less than 0.05), autonomy (bed-ridden patients, p less than 0.05), medical history (more than 4 associated organ defects, p less than 0.01) and malignant disease (p less than 0.001). The most pejorative complications in terms of mortality appeared to be postoperative septic shock, a pulmonary complication or a neurological complication. Cardiovascular disease, frequently reported in the history of theses patients, did not appear to specifically affect mortality. Surgery in patients over the age of 90 years appears to be justified in active patients in good general health presenting with a benign disease likely to become complicated if not treated, which should be preferably operated electively. PMID- 2270916 TI - [Surgical imperatives in pancreatic transplantation in dogs]. AB - The authors report their experience of segmental pancreatic autotransplantation in dogs. The most reliable model seems to be: segmental heterotopic pancreas transplantation with bladder diversion of the exocrine secretion and spleno splenic arterio-venous fistula allowing monitoring of the exocrine secretion and a reduction in the thrombosis rate. PMID- 2270917 TI - [Manometric study of two Roux-en-Y hepatico-jejunostomy]. AB - The aim of this study was to describe (during the fasting state in two patients the motor activity of the limb in Roux-en-Y hepatico-jejunostomy). In the two patients, the limb was created 15 years and 15 days prior to the study respectively. Recordings were performed with a low compliance pneumohydraulic system below the jejuno-jejunal anastomosis then in the limb. Motor studies in the limb were coupled with recordings carried out in the duodenum. In both patients, the regular occurrence of a typical phase III (PIII) activity was demonstrated in the limb whereas no retrograde or abnormal motor patterns were found. PIIIs in the limb were uncoordinated with duodenal PIIIs. Trimebutine, given intravenously, induced a typical PIII activity in the duodenum and the limb simultaneously. Spontaneous or trimebutine-induced PIIIs in the limb had a slower migration velocity (p less than 0.01) than duodenal PIIIs. Lastly, we were unable to record PIIIs in the distal jejunum below the jejuno-jejunal anastomosis despite the lack of associated abnormal motor patterns. This study demonstrates that a normally propagated PIII activity can be observed in the limb in Roux-en-Y hepatico-jejunostomy immediately or several years after the surgical procedure. PMID- 2270918 TI - [Reoperation in severe hepatic trauma. 30 cases]. AB - From 1978 to 1987, thirty patients were secondarily referred to Saint-Antoine Hospital for the treatment of their hepatic trauma. Seventeen were referred because of a postoperative complication (group I) and thirteen after peri-hepatic packing (group II). In group I, transfer was decided because of hemorrhage (8 patients), sepsis (6 patients) and haemobilia (3 patients). The lesions observed in this group (hemoperitoneum, hepatic sequestrum, intrahepatic hematoma, choleperitoneum and subphrenic abscess) were often related to an incomplete assessment of hepatic damage due to an inadequate exploration and the absence of operative cholangiography. In group II, peri-hepatic packing was effective in eleven patients. The overall mortality was 16.6% (17.6% in group I and 15.4% in group II). Postoperative complications occurred in 50% of the patients (64.6% in group I and 30.7% in group II). Good exposure of the liver, operative cholangiography and, in selected cases, a direct approach to the lacerated liver with suture ligation of severed blood vessels and bile ducts are mandatory for the complete exploration and the treatment of severe hepatic trauma. Peri-hepatic packing and the transfer of the patient to a specialized center is a reliable method when the injury cannot be treated locally. PMID- 2270919 TI - [Etiology, diagnosis and treatment of hepatic abscesses after biliary tract surgery]. AB - The majority of hepatic abscesses of biliary tract origin are the result of suppurative or non suppurative cholangitis, caused either by common duct stones, inflammatory stricture or malignancies. We report our experience of 7 consecutive liver abscesses after biliary tract surgery, treated in our surgical unit over a 2-year period, there were 6 females and 1 male with an age of 41 to 83 years. Hepatic abscess after biliary surgery developed from 10 days to 14 months postoperatively. Two patients underwent primary surgical drainage and remained clinically well 6 months and 2 years postoperatively. Five patients initially had percutaneous drainage and 4 of them subsequently underwent operative drainage; one patient declined any further operative treatment after percutaneous drainage and died 8 days later from continuing sepsis. Multiple factors may account for the development of both cholangitis and hepatic abscess following biliary tract procedures. Radiologic investigation should not only focus on the abscess itself but must also identify underlying biliary pathology. Our experience suggests that a surgical approach may be preferable to percutaneous techniques as it allows appropriate management of the associated biliary pathology. PMID- 2270920 TI - [Disposable obturator system for colostomized patients. Experience with thirty patients over one year]. AB - The objective of this study, conducted according to a specially designed protocol, was to evaluate the efficacy of a disposable obturator in patients with an artificial anus. The obturator was tested for 1 year in 30 patients with a colostomy. The characteristics of these patients, the system adopted for training and follow-up and the results obtained are analysed. The disposable stopper gave favourable results as a contention system; the tolerance was good and no adverse effects were observed. In particular, the patients appreciated the absence of noise and odour and the security offered by this system. The contention systems in current use are reviewed followed by a discussion based on their experience and their results. PMID- 2270921 TI - [The patient-machine-physician relation]. PMID- 2270922 TI - [Calculous anuria in children. Apropos of 12 cases]. AB - The authors report their experience of calculus anuria in children. They based their study on a series of 12 cases. They point out, in particular, the diagnostic difficulties and prognostic risks which could be encountered. They also emphasize, the role of prompt renal drainage in the management of such an emergency and recommend percutaneous nephrostomy followed by cold nephrolithotripsy. PMID- 2270923 TI - [Focus on vesicovaginal fistulas at the Yaounde Central Hospital. Apropos of 111 cases seen in 10 years]. AB - The authors discuss the vesicovaginal fistulas seen at the Central Hospital in Yaounde. Rectomyoplasty was widely used for treatment. Fortunately, public health policies have succeeded in reducing the incidence of this condition. PMID- 2270924 TI - [The significance of the use of fibrin glue in complete cystectomy with urinary diversion]. AB - Two groups of 15 patients were submitted to radical cystoprostatectomy with urinary diversion. Was used in one group. Fibrin glue appears to be a valuable progress to improve the immediate follow-up of these patients, in terms of morbidity and the duration of parenteral assistance. PMID- 2270925 TI - [Pyelo-ureteral junction syndrome in a transplanted kidney]. AB - The authors report a case of decompensated pyelo-ureteric junction obstruction in a renal transplant patient with anuria on the 27th day, while the IVP (on the 22nd day) was normal. They compare this case with the literature. PMID- 2270926 TI - [Retroperitoneal lipomas in children. Apropos of a new case. Review of the literature]. AB - Retroperitoneal lipoma is a rare tumor in children and is usually benign. A case in a 29 month old girl is reported together with a review of the 18 previously documented cases. The patients ranged in age from 1 to 8 years. Girls are affected three times as often as boys. The majority had a enlarged abdomen of long duration. Most lipomata were large. However, the tumor was easily removed. There have been no known recurrences following operative resection. A child with such a tumor should be followed until more clinical experience has been acquired. The possibility of these tumors being congenital in children cannot be excluded. PMID- 2270928 TI - [The surgeon specialist urologist facing medical responsibility. Practical notes]. AB - Over recent months, various medical societies have held sessions about this delicate subject which have focussed more on information than discussion, reflecting a certain degree of concern. Professionals, i.e. legal or private experts have always met in specialized societies, occasionally inviting jurists, magistrates or insurance company legal advisers to participate in their discussions. However, the debates between specialists largely escape the non specialist doctor. In general medical societies, any discussion which follows a basic presentation is too often diverted towards particular details and personal cases. Some meetings present "informal chats" which give the listener the erroneous impression of having being informed. It is very difficult to practically and usefully inform colleagues, but the author nevertheless attempts this task. The first part of the article presents the classical internship questions in the form of "management of a case of...". The second, legal part concisely defines the situations of various types of doctors in relation to medical responsibility and briefly deals with the general problem involved. The author has a limited experience despite certain encouragement to apply for inscription on the list of expert surgeons as well as that of expert urologists, the author only applied to be an expert urologist, a role he has filled for the last 28 years. He has seen slightly more than 40 cases of urological medical responsibility. The doctors concerned were essentially urologists, gynaecologists, "gastrointestinal" surgeons and even orthopaedic surgeons. However, general practitioners have also been implicated for failing to take urgent and necessary measures required by the patient's condition. PMID- 2270927 TI - [Anuria associated with an aorto-iliac aneurysm. Apropos of a case]. AB - The authors report a case of a perianeurysmal retroperitoneal fibrosis (RPF) with oligoanuric renal failure. A complete assessment was performed with computed tomography. Bilateral ureteral catheterization restored normal renal function and allowed surgical treatment to be performed including an aorto-iliac replacement and a bilateral ureterolysis with intra-peritoneal diversion of the ureter. A review of the literature revealed 15 similar cases. Pathophysiology and treatment of the retroperitoneal peri-aneurysmal fibrosis are discussed. PMID- 2270929 TI - [The treatment of pelvic ureteral calculi using the Dornier lithotripter. Apropos of 20 cases]. AB - The authors report a series of twenty patients with pelvic ureteric stones treated by the Dornier lithotriptor. Sixteen men and 4 women were treated over a period of 8 months (November 1988 and June 1989). A single treatment session was sufficient to ensure destruction and elimination of the stones. This technique, which does not require anaesthesia, but at most simple neuroleptanalgesia, has a low morbidity (15%). In the series of 20 patients: the stones were completely eliminated in 16 cases, 1 case was a failure at 3 months and 3 patients were not reviewed. These results are assessed with a minimum follow-up of three months and a maximum follow-up of eight months. This simple, rapide, repeatable and effective therapeutic technique appears to constitute an alternative to operative endoscopy (flexible or rigid ureteroscopy) in the treatment of stones of the pelvic ureter. PMID- 2270930 TI - [Ambulatory urologic surgery]. AB - Since November 1st, 1988, an outpatient clinic has been set up in our department of Urology. Patients come to the clinic on the morning of the procedure and leave in the evening after a few hours of monitoring. Eligibility for outpatient surgery is determined using strict social, surgical and medical criteria. A visit with the anesthesiologist is scheduled one week before the operation. On the day of the procedure, the patient arrives at 7 a.m., is shaved, prepared and operated on by a senior surgeon before impatient operations begin. Postoperative monitoring is carried out as usual and around 6 p.m. the surgeon and the anesthesiologist decide whether the patient can be discharged. Most patients are interviewed by telephone within one week of the procedure. From November 1988 through December 1989, 172 adults were admitted to the outpatient clinic for endoscopic surgery (85 cases), open surgery (42 cases) or other procedures including diagnostic investigations, instillations, and removal or replacement of stents (44 cases). Twenty-three patients were discharged only on the day following the procedure. One patient was readmitted for clotting in the bladder. These preliminary results show that, as compared to inpatient surgery, outpatient surgery is cost-saving, easier to cope with psychologically and less apt to be followed by nosocomial infection, without greater risk to the patient provided inclusion criteria are stringently applied. PMID- 2270931 TI - [A critical study of the prognosis of renal adenocarcinoma and an attempted classification. Apropos of a series of 322 cases]. AB - The prognosis of adult renal adenocarcinoma was evaluated by analyzing 322 cases treated by extensive nephrectomy (1979-1988). Five-year actuarial survival curves showed that prognosis was closely correlated with anatomic spread: no clear prognostic significance could be ascribed to venous invasion but involvement of retroperitoneal lymph nodes proved to be nearly as negative a prognostic factor as metastatic disease. The grade of malignancy also had a major impact on prognosis. Because the TNM classification, although accurate, is difficult to use and relies solely on descriptive data, a simple five-stage classification is proposed but remains to be validated. The classification system advocated by Robson groups stages with very different outcomes and consequently seems unhelpful. PMID- 2270932 TI - [Cystic cancer of the kidney]. AB - Four cases of cystic renal adenocarcinoma in adults free of renal dysfunction are reported. The authors propose a diagnostic approach for atypical cysts that takes the new imaging techniques into account (ultrasonography and CT scan initially, MRI subsequently). A practical therapeutic strategy is also described: because intraoperative histologic diagnosis is difficult partial nephrectomy to allow an intraoperative study of the entire cyst is advocated; extensive nephrectomy, which is the only procedure that ensures total exeresis of the carcinoma, is performed either immediately if the intraoperative study of the cyst or of its aseptic necrotic and hemorrhagic content is positive, or later if subsequent histologic studies reveal a malignancy. PMID- 2270933 TI - [Computer stimulation of endoscopic resection of the prostate]. AB - The number of urologists in need of training is increasing whereas the number of resections of the prostate is falling. Patients are less and less willing to have their procedure serve for young residents to learn the technique of endoscopic resection of the prostate. Despite teachings and videoendoscopy, this procedure remains difficult to learn. We decided to develop a simulator for endoscopic resection after having seen the remarkable model of endoscopic simulation developed by French gastroenterologists and presented at the computer science workshop of the AFU symposium. The hypercard program, the laservision disk, and the CD ROM project were elected as a good introduction to this challenging although not unsurmountable problem. We had to adequate our goals to the resources of French urologists: the Macintosh II is the most sophisticated affordable computer. Computerization of the televised images of the endoscopic procedure and formalization of the gestures of the operator are required. Conventional image synthesis programs for use with the Mac II are either very slow or very limited. Conventional simulation programs are highly mathematical. Computerized images take up considerable memory space and large capacity disks or optical disks are required. The urologic laservision to which we contributed in 1986 contains few endoscopic images of the prostate but served as a basis for devising a methodology. Object programming with hypercard and animated image programs for Macintosh computers will be the starting points for our project that will benefit from the significant advances announced by Apple concerning color image file maintenance. PMID- 2270934 TI - Duplicate publication and related problems. PMID- 2270935 TI - Surgery for gastro-oesophageal reflux. PMID- 2270936 TI - Rectal temperature of normal babies the night after first diphtheria, pertussis, and tetanus immunisation. AB - Continuous rectal temperature recordings were made from 32 babies the night after their first diphtheria, pertussis, and tetanus immunisation and compared with recordings made before immunisation. Tog values of clothes and wrapping and room temperatures were also recorded. We found that immunisation the day before disturbs the normal night time rhythm of deep body temperature. The rectal temperature of immunised babies was significantly higher than non-immunised babies from two hours into the night. We also found that there were considerable individual variations in the extent of disturbance of temperature rhythm. They were not correlated with thermal environment. There is no reason to suppose that these mild physiological responses to immunisation are in any way harmful. PMID- 2270937 TI - Factors influencing the body temperature of 3-4 month old infants at home during the day. AB - Continuous recordings of rectal temperature were made from 40 normal infants, aged 3-4 months, at home during two days of normal activities. We found that the rectal temperature of a normal, healthy baby may vary from 36.0 degrees C at night to 37.8 degrees C during active periods of the day. During daytime sleep rectal temperature fell, but to a lesser extent, and for less time than during night time sleeps. Feeds raised the temperature unless the baby slept, when they reduced the rate of fall of temperature. Bottle feeds affected temperature more quickly than breast feeds. The changes in temperature during sleep and after feeds were independent of the room temperature or thermal insulation of clothing and wrapping. PMID- 2270938 TI - Growth velocity before sudden infant death. AB - Weight velocities of 136 infants who died from sudden infant death syndrome (SIDS) were compared with those of 136 controls matched for sex, birth weight, and type of feeding. It was found that the SIDS infants gained weight more slowly overall and that the differences were significantly different for infants who were not breast fed in the last two weeks in which it was possible to estimate their growth velocity. Breast fed infants had more periods of growth below the 25th centile than expected. These differences are unlikely to be useful in the prediction of which babies are likely to die from SIDS as there are frequent episodes of poor growth in infants who do not die. PMID- 2270939 TI - Increasing asthma prevalence in a rural New Zealand adolescent population: 1975 89. AB - A survey of asthma symptoms and spirometry in 435 adolescent schoolchildren was undertaken in 1989 in a rural, largely Maori population. The survey questionnaires were identical to those used in a 1975 survey at the same school. The prevalence of reported asthma or wheeze significantly increased from 26.2% to 34.0%. This increase occurred in groups reporting asthma, and also those reporting wheeze unassociated with colds, but without a previous diagnosis of asthma. There was a tendency for a rise in reported wheeze in Europeans (24.3% to 27.4%) and a significant rise in Maoris (27.1% to 36.2%). The reclassification of other respiratory problems did not account for the increase. Data from this study provides evidence that there has been a rise in the prevalence of asthma in this New Zealand population over a time period of 14 years. PMID- 2270940 TI - Long term outcome of ventilated asthmatics. AB - Over a 25 year period, 31 asthmatic children received artificial ventilation for acute asthma at Alder Hey Children's Hospital on 48 occasions. Altogether 47 episodes occurred from 1971-89, with no decline in the number of episodes per year (mean 2.5) over this period. Eight children died during intermittent positive pressure ventilation (IPPV), and of the 23 survivors, three further children had subsequently died from asthma. Seventeen children were followed up for more than a year after IPPV. Sixteen still had symptoms of asthma and over half had symptoms every day. Ten cooperated with pulmonary function tests: mean forced expiratory volume in one second was 83% of predicted and geometric mean provocative histamine concentration (PC20) was 2.1 mg/ml. Since the follow up study a fourth patient had died from asthma. IPPV continues to be required for a small number of asthmatic children each year. The survivors remain a high risk group with significant continuing morbidity and mortality. PMID- 2270941 TI - Human isophane or lente insulin? A double blind crossover trial in insulin dependent diabetes mellitus. AB - Fifty two children with insulin dependent diabetes mellitus were randomised to receive human isophane or lente insulin preparations in combination with soluble insulin in a double blind trial. Patients were seen every two months, and crossed over after four months of treatment. Control assessed by glycated haemoglobin was significantly lower in children on human isophane insulin, but fasting blood glucose and fructosamine concentrations and the number of episodes of hypoglycaemia were similar on both regimens. In five children on twice daily insulin regimens, insulin profiles throughout a 24 hour period demonstrated greater variability on lente compared with isophane insulin despite identically administered insulin doses. A questionnaire completed at the end of the study showed that two thirds of the children and/or their parents preferred the isophane insulin, and they gave perceived improvement of metabolic control as the major reason for their choice. PMID- 2270942 TI - The reliability of height measurement (the Wessex Growth Study). AB - The two major components of reliability are accuracy and reproducibility. Three studies of the reliability of height measurement in children are reported. In the first, a standard metre rod was used to spot check the accuracy of installation of 230 measuring instruments in one health district in Wessex, UK. The readings obtained ranged from 90.0 to 108.5 cm and showed the urgent need for the positioning of instruments to be regularly checked. In a second study, to examine the reproducibility of height measurement, two experienced observers measured 10 young children (106.0 to 152.0 cm), three times on five instruments of different design. The observations were blind and in random order. The estimated standard deviation for a single height measurement was generally in the range 0.2-0.3 cm. Over 95% of the variance was attributable to the child, very little to the instrument or observer. Finally, the conditions of the second study were modified to examine the effect on reproducibility of non-blind and non-randomised measurements, as usually occurs in the clinic. A lower but inevitably false estimate of the error was obtained. It is recommended that the error of height measurement, appropriately established and expressed in simple terms, be stated in every published growth study. PMID- 2270943 TI - Are measurements of height made by health visitors sufficiently accurate for routine screening of growth? AB - To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study. Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors. They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer. For a single assessment of height both pieces of equipment gave reasonably accurate results. In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm. At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm. The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements. We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training. PMID- 2270944 TI - Late deaths after treatment for childhood cancer. AB - An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other cause unrelated to the tumour or its treatment, 44 (6%). Less than 10% of five year survivors of non-Hodgkin lymphomas, neuroblastoma, retinoblastoma, Wilms' tumour, or a soft tissue sarcoma died of recurrent tumour during the next 15 years, while more than 25% of five year survivors of Hodgkin's disease, ependymoma, medulloblastoma, and Ewing's tumour died of recurrent tumour during the corresponding period. Almost 50% of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years, a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given. Comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non-neoplastic causes. Five times the expected number of deaths from cardiovascular causes were observed, these were predominantly myocardial infarction and cerebrovascular accidents. There was no evidence of an excess in the number of suicides observed, but there were three times the expected number of deaths from accidents observed after central nervous system tumours. Two groups of patients were identified whose deaths were potentially avoidable. Seven patients with craniopharyngioma and panhypopituitarism presented with addisonian crises during periods of stress not adequately covered by exogenous corticosteroids. In the other group were children who received radiotherapy and later developed problems related to radiation fibrosis. We emphasize that our investigation relates to patients diagnosed with childhood cancer before 1971. The pattern of mortality that will emerge after recent treatment regimens, in which chemotherapy is being used more extensively, is likely to be different from that observed in our study. PMID- 2270945 TI - Diagnosis of Pneumocystis carinii pneumonia from non-invasive sampling of respiratory secretions. AB - An infant infected with HIV presented with fever, tachypnoea, hypoxia, and radiological evidence of bilateral pneumonitis. Fluorescent antibody technique identified Pneumocystis carinii within 24 hours from secretions obtained by nasopharyngeal aspiration. This rapid, non-invasive method should be the first line investigation of suspected P carinii pneumonia in immunocompromised patients. PMID- 2270946 TI - Nocturnal faecal soiling and anal masturbation. AB - Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied. The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted. We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised. PMID- 2270947 TI - Development of a psychiatric liaison service. PMID- 2270948 TI - Pulmonary hypertension in bronchopulmonary dysplasia. PMID- 2270949 TI - Serum immunoglobulins in acute lymphoblastic leukaemia. PMID- 2270950 TI - Reduced sweating in Laron's dwarfism. PMID- 2270951 TI - Air pollution and fatal lung disease in three Utah counties. AB - A unique situation found in two Utah counties has made it possible to estimate the fraction of respiratory cancer and nonmalignant respiratory disease (NMRD) deaths, which are attributable to community air pollution (CAP) in one county. The two counties were very similar in many ways, including low smoking rates, until a steel mill constructed during WW II caused substantial CAP in one of them. Subsequent differences in mortality rates from both respiratory cancer and NMRD are striking. A third county, similar to many counties outside Utah, was included in the analysis for comparison. In one county, 30-40% of the respiratory cancer and NMRD deaths were attributable to CAP. In this county, NMRD deaths (but not respiratory cancer deaths) were slightly more frequent than in Salt Lake County where smoking rates were twice as high. PMID- 2270952 TI - X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposure. AB - A k-x-ray fluorescence (K-XRF) instrument that can measure in vivo bone lead at low levels was used on a population of 34 adults with no known history of excessive lead exposure. A questionnaire that gathered information relevant to occupational and environmental lead exposure was administered prior to the measurement. A 30-min measurement that produced an average estimated uncertainty of 6 mcg lead/g bone mineral was taken at the mid-tibial diaphysis for each subject. Eighteen subjects had bone lead levels below the measurement uncertainty. The remainder had bone lead levels ranging up to 21 mcg lead/g bone mineral. Bone lead levels were greater among older subjects. Among young adult subjects, bone lead levels greater than the measurement uncertainty were confined entirely to subjects who had grown up in housing that was estimated to have been build prior to 1955. Such a childhood environment is at high risk of fostering exposure to biologically absorbable lead through ingestion of lead paint contaminated dust and lead pipe-contaminated water. We conclude that the K-XRF technique has the potential to distinguish between low levels of lead burden in epidemiologic studies. PMID- 2270953 TI - Low-level lead exposure in the prenatal and early preschool periods: language development. AB - Inconsistent results continue to be reported from studies linking low-level lead exposure and child development. This inconsistency is seen for both prenatal exposure and exposure in the preschool years. The primary outcome measures in most reports are indices of cognitive development, including IQ. Verbal skills may be particularly vulnerable to toxic insult. The fact that 2 y of age is both a time of peak exposure and also a time of rapid language development suggests that this may be a critical period for such an effect. The later prenatal and early infancy period, at which time the nervous system is developing rapidly, may also be critical exposure period. We examined the relationship of maternal and cord blood lead (PbB) at birth and venous PbB at 6 mo, 2 y, and 3 y with language measures at 1, 2, and 3 y of age. The sample consisted of disadvantaged urban children. Multivariate analyses revealed no statistically significant relationship of either prenatal PbB or early preschool PbB with language measures after control of cofactors. Supplementary partial correlations revealed a marginal relationship of cord PbB and mean length of utterance (MLU), which describes a child's ability to form meaningful word combinations. Because this analysis was one of a large number of analyses with both positive and negative regression coefficients, the possibility that this was a chance effect was considered. If there is an effect of low-level lead exposure on language development, that effect is not robust. PMID- 2270954 TI - Prenatal exposure to methyl mercury among Greenlandic polar Inuits. AB - During the period 1982 to 1988, 37 paired samples of blood from Inuit women and their newborn children were collected in North Greenland. The samples were analyzed for whole blood content of total mercury (tot-Hg) and for content of methyl mercury (Me-Hg). In maternal blood, 80% of the tot-Hg was found to be methylated in contrast to 98% in cord blood. Concentrations of Me-Hg in maternal and cord blood were significantly correlated, and the mean ratio between fetal and maternal blood Me-Hg was 1.9. Concentrations of Me-Hg in cord blood were closely related to the marine food intake of the mothers. Eighty-four percent of the mothers had blood concentrations of Me-Hg above 0.11 mumol/l (23 micrograms/l), which corresponds to the provisional limit of tolerable intake set by the World Health Organization. This indicates that the majority of the pregnant woman have an unacceptable high intake of methyl mercury. PMID- 2270955 TI - Ingestion of carcinogenic N-nitrosamines by infants and children. AB - Volatile N-nitrosamines are very potent carcinogens. They can be approximately 5 million times more powerful than saccharin. One of two principal methods is generally used when assaying rubber products for nitrosamine content: (1) the German method (aqueous extraction) or (2) the U.S. method (dichloromethane extraction). When 16 types of baby-bottle nipples and children's pacifiers were tested recently, relatively high levels of nitramines, nitrosamines, and nitrosatable precursors were found. Eighty-one percent failed to meet the strict Dutch standards (based on the German method), but only 37.5% would have been banned according to U.S. regulations, which ignore nitrosatable-precursor content. Up to one-third of the nitrosamines present in a rubber nipple may migrate into the milk in the bottle within a few hours. Transfer into infant formula may exceed 40%, and transfer into saliva may be even higher. Thus, a highly contaminated nipple may cause a 5-kg infant who drinks 1 l/d to ingest approximately 2 micrograms/kg body weight.d of nitrosamines. To this, add any exposure resulting from pacifier use or from in vivo nitrosation of precursors. Therefore, daily exposure of infants may, in the worst case, conceivably reach 4 5 micrograms/kg body weight.d. Entire average daily exposure of an American adult to volatile nitrosamines from major sources is estimated to be less than 0.05 micrograms/kg body weight.d. Infants who use products like those tested may, therefore, be exposed daily to less than or equal to 100 times more of these carcinogens than are adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270956 TI - Acute myeloid leukemia and background radiation in an expanded case-referent study. AB - A case-referent study that investigated possible associations between environmental and occupational exposures and acute myeloid leukemia was performed on 86 cases and 172 referents, all of whom were living. Exposure information was obtained through a questionnaire mailed to each subject. An association was found between time spent in concrete buildings at home and work and leukemia morbidity. In addition, extensive x-ray examinations that occurred more than 5 y prior to diagnosis were more common among cases than referents. PMID- 2270957 TI - Health effects of volcanic ash: a repeat study. AB - The Mount Sakurajima volcano in Kyushu, Japan, is proximal to a large residential area, and it emits an enormous amount of volcanic ash during frequent eruptions. In our previous study, we investigated, for the first time, respiratory effects of chronic exposure to volcanic ash. The study demonstrated a low prevalence of respiratory symptoms, even in the area of highest exposure; only a slight excess prevalence of symptoms appeared to be associated with exposure to volcanic ash. To confirm the findings of our previous study, the prevalence study of chronic respiratory symptoms for residents was repeated in Kanoya and Tashiro, which are located 25 and 50 km, respectively, from the crater of Mt. Sakurajima. The concentration of suspended particulate matter in Kanoya frequently exceeded the national environmental quality standards and, during summer and winter, was 2-3 times higher than that found in Tashiro. Women who were 30-59 y of age and who had resided in Kanoya or Tashiro for more than 3 y completed a modified ATS-DLD questionnaire. The prevalence of nonspecific respiratory disease was low, i.e., 6.5% in Kanoya and 6.2% in Tashiro; similar prevalences were found in women who had never smoked. When we restricted the analysis to individuals without a history of occupational exposure to dusts and who had no exposure to passive smoking, there was a slightly higher prevalence of nonspecific respiratory disease in Kanoya than Tashiro, but the difference was not significant. Eye symptoms were equally prevalent in the two areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2270958 TI - Giant cell arteritis (temporal arteritis) affecting the breast: report of two cases and review of published reports. AB - The breast is an infrequently recognised site of primary giant cell arteritis. Two cases of giant cell arteritis affecting the breast are described and 11 previously described cases are reviewed. All cases presented with single or multiple breast masses, leading to a diagnosis before biopsy of suspected breast carcinoma. Symptoms similar to those of polymyalgia rheumatica occurred in about half of these patients, though the significance of these symptoms was only appreciated in retrospect. Clinical or pathological evidence of giant cell arteritis outside the breast (temporal artery, thyroid artery) was noted in a minority of cases. Seven patients received corticosteroid treatment, and all patients recovered without complications. Two patients had an adenocarcinoma of the breast contiguous with the giant cell arteritis. Giant cell arteritis affecting the breast may be underrecognised and should be considered in older women with polymyalgia rheumatica-like symptoms and tender breast mass(es). PMID- 2270959 TI - Septic arthritis complicating apatite associated destructive arthropathy. AB - Septic arthritis can complicate many forms of arthritis. Two cases of apatite associated destructive arthropathy (AADA) complicated by sepsis are described. Diagnosis of this complication in the setting of severe joint damage is difficult as AADA and sepsis share certain characteristics--an initial, rapidly progressive, severely painful course and radiographs which show rapidly destructive changes with marked cartilage loss, bone attrition, and virtual absence of osteophyte or cyst response. PMID- 2270960 TI - Munchausen's syndrome simulating reflex sympathetic dystrophy. AB - A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admissions to hospital and multiple explorations we discovered that she had induced her symptoms herself and a diagnosis of Munchausen's syndrome was made. As far as we know this presentation has not been previously reported and might help to explain the physiopathology of some signs of reflex sympathetic dystrophy. PMID- 2270961 TI - Bone mineral density levels in elite female athletes. PMID- 2270962 TI - Nodal generalised osteoarthritis is an autoimmune disease. PMID- 2270963 TI - Drugs and the elderly. PMID- 2270964 TI - Cardiac tamponade in juvenile chronic arthritis. PMID- 2270965 TI - Dynamic injection of the digital flexor tendon sheaths. PMID- 2270966 TI - Pigmented villonodular synovitis. PMID- 2270967 TI - Autoantibodies and antibacterial antibodies: from both sides now. PMID- 2270968 TI - Autoantibodies in patients with juvenile chronic arthritis and their immediate family relatives. AB - Antibodies to nuclear antigens were assessed in 23 children with juvenile chronic arthritis (JCA) and 66 of their first degree relatives. Serum samples from 16 patients with JCA (70%) and nine relatives (14%) had antinuclear antibodies by indirect immunofluorescence. Antibodies against nuclear antigens in rabbit thymus extract or an erythroblastoid cell line (K562) were detected by countercurrent immunoelectrophoresis and immunoblotting in 16 patients (70%) and 39 family relatives (59%). Immunoblotting did not show any banding patterns common to all patients with JCA, though bands in the 43-45 kD range were detected in 5/23 patients. Anticardiolipin antibodies were found in 7/23 patients. In total, 18/20 families (90%) had members other than the probands with detectable autoantibodies. In five families immunoblotting showed common banding patterns between the probands and other members. This suggests that there might be an inherited trend towards autoimmune responses in some families of patients with JCA. PMID- 2270969 TI - DQw7 and the C4B null allele in rheumatoid arthritis and Felty's syndrome. AB - DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompatibility complex (MHC) DQw7 allele (86% of DR4 positive patients with Felty's syndrome and 53% of DR4 positive controls) and the class III MHC C4B null allele (50% of patients with Felty's syndrome and 20% of DR4 positive controls). DQw7 and the C4B null allele are in linkage disequilibrium and the B44-Bf *S C4A*3-C4B*Q0-DR4-DQw7 haplotype accounts for five of 24 DR4 positive haplotypes assigned in subjects with Felty's syndrome. The results were not accounted for by articular disease severity and suggest that articular and extra-articular forms of rheumatoid disease may be immunogenetically heterogeneous. PMID- 2270970 TI - Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption. AB - In a search for aspects of behaviour related to oral contraceptive use which might explain the favourable effect of oral contraception on the onset of rheumatoid arthritis (RA), cigarette smoking and alcohol consumption were studied as possible risk factors. Information on cigarette smoking and alcohol consumption was obtained by interview at the first visit to the outpatient clinic of 135 young women with confirmed definite or classical RA of recent onset and 378 control patients with soft tissue rheumatism or osteoarthritis. The diagnosis in all patients was confirmed by at least two years of follow up. Of the patients with RA, 44/135 (33%) were current cigarette smokers compared with 181/378 (48%) of the controls. The percentage of smokers among the controls was similar to that of women smokers in the general population. The adjusted risk of RA in women who smoked at least one cigarette a day was 0.61 (95% confidence interval (CI) 0.42 to 0.89). Thirty one (23%) patients with RA and 137 (36%) controls were alcohol drinkers. The risk of RA in women who consumed alcohol at least once a day was 0.52 (95% CI 0.33 to 0.84). The low relative risk estimates for cigarette smoking and alcohol consumption were mutually independent and also independent of oral contraceptive use, the presence of the HLA-DR4 antigen, or a positive family history of RA. The low incidence of alcohol consumption in the patients with RA might be due to the discontinuation of alcohol consumption after disease onset. The low incidence of cigarette smoking in the patients might reflect a protective effect of cigarette smoking on RA onset, possibly induced by changes in the immune system. PMID- 2270971 TI - Rheumatology at the general practitioner/hospital interface: a study of prevalence and access to specialist care. AB - Four general practices with a combined population of 23,300 in the west of Scotland participated in a record research and questionnaire assessment of 551 patients with rheumatic diseases. The study describes the prevalence, levels of disability found, and the types of service used. Even with this number of patients it was not possible to detect any significant differences in disability levels, use of second line drugs, or aids/appliances when comparing practices with adequate or inadequate access to rheumatological facilities (general practitioner perception). General practice is an appropriate setting in which to investigate the effect of service provision, but larger studies will be needed to reach more definite conclusions. PMID- 2270972 TI - Quantitative analysis of walking in patients with knee osteoarthritis: a method of assessing the effectiveness of non-steroidal anti-inflammatory treatment. AB - Most therapeutic tests of osteoarthritis treatments are assessed by criteria based either on fundamental data or on clinical data, which is often subjective. A quantified analysis of locomotion can be used to determine the spatiotemporal indices (stride length and duration), kinematic indices (walking speed, velocity peak), and symmetry criteria that are relevant to the assessment of locomotor handicaps in patients with osteoarthritis. This study examined the progression of locomotor abilities in 11 subjects aged 49-69 (mean 60.9) years with knee osteoarthritis before and after treatment with a non-steroidal anti-inflammatory drug. Naproxen sodium (1100 mg) was given once a day for seven days. The condition before and after treatment was evaluated by quantitative analysis of locomotion, estimation of pain on a visual analogue scale, and assessment of the degree of functional disability. Significant improvement in locomotor indices (proportional increase in walking speed 17.8%) and in degree of pain (proportional decrease 27%) as estimated on the analogue scale was found after non-steroidal anti-inflammatory drug treatment. The lack of a significant correlation between the decrease in pain experienced by the patients and the objective improvement of their functional capabilities emphasises the need in further studies of new treatments to accompany the patients' own assessments of self improvement with a quantitative analysis of the way in which they walk. PMID- 2270973 TI - Brucella arthritis: a study of 96 cases in Kuwait. AB - Of 400 patients with brucellosis, 104 (26%) had arthritis, of whom 96 could be followed up. The systemic disease in the 96 patients was acute in 54 (56%), subacute in 24 (25%), and chronic in 18 (19%). The main presenting symptoms were joint pain, fever, sweating, and easy fatigability. The joints most commonly affected were the sacroiliac joint (26%) and knee (25%) followed by hip (18%) and spine (8%). There was no particular pattern of joint affection in relation to age. Joint effusion occurred in 32/104 (30%) of cases, predominantly (94%) in the acute group. Culture of synovial fluid was negative in all, and analysis of synovial fluid for cellular profile, glucose, and protein content was not particularly helpful in diagnosis. Plain radiographs did not show major pathological changes. Among the laboratory tests, including haematological and liver function tests, the brucella enzyme linked immunosorbent assay (ELISA) was the most reliable in the diagnosis of disease, using serum and synovial fluid specimens. Treatment with a combination of streptomycin plus tetracyclines or rifampicin resulted in an excellent cure rate and resolution of arthritis without sequelae or mortality. Thus brucellosis should be considered in the differential diagnosis of arthritis, especially in areas in which the disease is endemic. PMID- 2270974 TI - Sparing effect of hemiplegia on scleroderma. AB - The paretic limb is spared in patients who develop rheumatic diseases after a hemiplegic stroke. This has been described previously in rheumatoid arthritis, gout, and osteoarthritis. A similar presentation in a case of scleroderma is described in this report. Scleroderma skin changes are absent in the completely paretic limb and were markedly reduced in the weak left leg. Inflammation may be modified either by neuropeptides or by an anatomical neurological lesion and this may explain the phenomenon. PMID- 2270975 TI - [The morphological characteristics of dysplastic changes in the endometrium]. AB - Morphological characteristics of endometrial precancerous changes (dysplasia) are given with special reference to the degree and the direction of differentiation (endometrial, metaplastic). On the basis of these data the signs of endometrial carcinoma are standardized. PMID- 2270976 TI - [Ovarian endometriosis]. AB - Study of 52 patients with ovarian endometriosis supports the point of view about the relative autonomy of ovarian endometriosis from the cyclic hormonal alterations in female organism. In the foci of endometriosis the signs of differentiation of the epithelium by both tubal and endocervical types are revealed. This enables one to admit the possibility of ovarian serous and mucinous carcinoma development from the foci of endometriosis. Marked dysplastic changes, up to the focal carcinoma, are revealed but there were no signs of invasion. In the genesis of endometrioid carcinoma the great importance is attributed to the step-like process: endometriosis----borderline endometrioid tumour----endometrioid cancer. PMID- 2270977 TI - [Flow cytometry in the evaluation of the prognosis and course of malignant soft tissue tumors]. AB - Investigation of DNA content by flow cytometry method (determination of ploidy and cell proliferation activity) carried out in 45 patients with malignant and 19 patients with benign tumours revealed diploid distribution of DNA in 18 cases and aneuploid in one case of benign tumours. DNA distribution in malignant tumours was diploid in 23 cases (51.1%) and aneuploid in 22 regardless of histological variant of the tumour. Diploid cells were always present in the aneuploid tumours and their number was higher in primary tumours than in recurrent tumours (only tumour cells were found in the cytological control smears). No full correlation is observed between indices of cell proliferation activity obtained by morphological and cytometric methods. Ploidy and proliferation activity (number of cells in S-phase of cell cycle) are prognostic criteria of the survival and duration of disease without recurrence. PMID- 2270978 TI - [Oncogenes, antioncogenes and carcinogenesis]. AB - Current concepts on oncogenes, "antioncogenes" and their role in tumorigenesis are presented. Normal functions of proto-oncogenes, mechanisms of their conversion to oncogenes and inactivation of "antioncogenes", effects of oncogenes in model systems in vitro and in vivo are considered. Special attention is paid to the nonrandom proto-oncogene and "antioncogene" alterations in human tumours and the possibilities of their use as diagnostic or prognostic criteria. PMID- 2270979 TI - [The epithelial junctional zones of the anal canal and cervix uterus: the ultrastructure of tumors of these zones]. AB - Relationships between squamous and columnar epithelia in the anal canal and cervix uteri of postnatal period and fetus were studied. The transitional stratified epithelial lining, which is called junctional epithelium, is interposed between the mentioned epithelia. The junctional epithelium has variable numbers of layers of epidermoid cells, which differ from cells of atypical squamous epithelium by some ultrastructural features of the cytoskeleton and cell surface and by a low content of glycogen. The hypothesis on the physiological significance of this epithelium is proposed. Ultrastructural features of the cytoskeleton and cell surface suggest that anal basaloid carcinomas and some cervical squamous carcinomas may develop from so-called junctional epithelium. PMID- 2270980 TI - [The morphological heterogeneity of mesangioproliferative glomerulonephritis]. AB - Three variants of mesangioproliferative glomerulonephritis (MPGN) are distinguished on the basis of quantitative and qualitative morphological study of 172 kidney biopsies. The first variant is characterized by subendothelial and mesangial deposits of IgA and C3 in the glomeruli, the lack of fibroplastically transformed (FT) glomeruli and small tubulointerstitial component (TIC), the predominance of the phagocytizing mesangial cells; the second variant by the subendothelial deposits in the glomeruli of IgM or IgM and C3, the absence of FT glomeruli and TIC, the presence of an equal number of phagocytizing and synthetizing mesangial cells. Glomerular deposition of IgG or the absence in the glomeruli of all immunoglobulins and C3, the presence of FT glomeruli and TIC, pronounced accumulation of mesangial matrix and moderate proliferation of predominantly synthetizing and fibrosing mesangial cells are characteristic of the third variant. Recognition of the MPGN variants allows one to understand the variety of its clinical manifestations and differing prognosis. PMID- 2270981 TI - [The disseminated intravascular coagulation syndrome in endotoxin shock]. AB - Dynamics of blood coagulation and morphological changes after the intravenous administration of Salmonella typhimurium endotoxin is studied experimentally in Chinchilla rabbits. The stages of blood coagulation are established characteristic for the above syndrome. The signs of the developing blood stasiopathy with the domination of vascular wall damage and thrombocyte aggregation are observed. No considerable consumption of the blood coagulation factors is found. It is concluded that a leading role in the pathogenesis of the endotoxin shock microcirculatory disturbances belongs to the vascular damage and aggregation thrombocytopenia and not to the coagulopathy consumption. PMID- 2270982 TI - [Changes in the muscular layer and the intermuscular nerve plexus of the intestines in experimental peritonitis in rats]. AB - Changes in the muscular layer and intermuscular nervous plexus are studied histologically, histochemically and electron microscopically using the model of faecal rat peritonitis. Alterations characteristic of water metabolism disturbances (edema) up to the coagulation or colliquative necrosis development of individual cells are revealed in the muscular layer. Damage to the cholinergic structures which can be interpreted as a reversible partial morpho-functional cholinergic denervation is found in the intermuscular nervous plexus. The above changes are the structural basis of the intestinal paresis in peritonitis. These changes are reversible if an early (up to one day) elimination of the inflammatory process occurs. PMID- 2270983 TI - [Uterine pregnancy and endometrial cancer]. AB - An observation of the uterine pregnancy combined with endometrial adenocarcinoma and uterine body endometriosis in a woman of 4.2 with the obesity of III degree, and hypertension is described. Chorion willi, decidual tissue, large pieces of the endometrium with decidual conversion of stroma and numerous monstrous closely packed glands with arrangement of nuclei in several rows and moderate mitosis are found histologically in the uterine curettage. Tumour cells formed at places solid bands with pseudocribrous structures. Uterus with its appendages was removed. Histologically reversible endometrial changes after the interrupted pregnancy are found with foci of an atypical glandular hyperplasia but without tumour elements. Endometriosis foci in the myometrium and a diffuse theca-cell hyperplasia in the ovaries are observed. PMID- 2270984 TI - [Aponeurotic fibromatosis with calcification]. AB - Clinico-morphological description of one case of aponeurotic fibromatosis with calcification in a 59-year-old man. Fibromatosis was localized in the proximal part of the limb and had a nodular appearance. Histologically, roundish and oval cells with "swollen" nuclei forming a sort of parallel rows, foci of calcification and chondroid metaplasia characteristic for such cases were found. PMID- 2270985 TI - [The structure of the pathalogicoanatomic diagnosis]. PMID- 2270986 TI - [A discussion of diagnosis (apropos the article by D. S. Sarkisov published in Arkhiv patologii No. 8 for 1990)]. PMID- 2270987 TI - [Modern nosological diagnosis (apropos the discussion article of D. S. Sarkisov)]. PMID- 2270988 TI - [The morphological diagnosis of malignant non-Hodgkin's lymphomas (lymphosarcomas)]. AB - On the basis of morphoimmunological correlates certain criteria have been elaborated helpful in diagnosis of non-Hodgkin's malignant lymphomas (NML) of both B- and T-cell origin, and this was reflected in the modified Kiel's classification. The group of T-cell NML has considerably increased. T-cell origin of Lennert's lymphoma and angioimmunoblastic lymphadenopathy has been proven. Morphological substrate of NML from peripheral T-lymphocytes became more precise. The tumours, depending on the predominant cells, are subdivided into small cell (T-zones and pleomorphic lymphoma of small cells), mixed cell (pleomorphic lymphoma of medium-size and large cells) and large cell lymphoma (immunoblastic and large cell anaplastic Ki-I+). Criticism of T-NML systematization is due to the lack of definite cytological criteria because of the extreme morphological heterogeneity of peripheral T-lymphocytes and different interpretation of the clinical course of the established morphological variants. Among B-cell lymphomas the problem of the so-called intermediate lymphocytic lymphoma (ILL) and its variety--a mantle-zone lymphoma as well as monocytoid B-cell lymphoma is discussed in the literature. It is established in immunological testing that the cells of ILL possess a phenotype of cells of the primary follicles and those of the mantle-zone of the secondary follicles while the cells of the monocytoid B cell NML have a peculiar unique phenotype similar to that of cells in the marginal zone of the spleen follicles. PMID- 2270989 TI - Periodic health examination. PMID- 2270990 TI - Could it be gallstones, doctor? AB - Gallstones may be asymptomatic, in which case they require no treatment. The author discusses symptomatic gallstones and the complications of gallstone disease. The type of presentation, appropriate investigations and treatment options are discussed. PMID- 2270991 TI - Irritable bowel syndrome. AB - The irritable bowel syndrome is characterised by symptoms of apparent gastrointestinal origin, in the absence of any demonstrable structural abnormality. The author emphasises the need for the exclusion of organic disease and outlines the minimum investigations required to achieve this. PMID- 2270992 TI - Large bowel cancer. Clinical approaches to improving survival. AB - Large bowel cancer is the commonest malignancy among Australians and has a high mortality rate. The author looks at ways to improve the survival rate of patients. PMID- 2270993 TI - Constipation. AB - The author outlines a safe diagnostic strategy for the symptom of chronic constipation, conforming to Australian Family Physician's series on common problems in general practice. The constipation is most commonly idiopathic, especially the simple form related to inadequate dietary fibre and bad habit. It is vital not to miss colonic or anorectal carcinoma. Important causes to consider include drugs (self administered or prescribed), hypothyroidism and depression. PMID- 2270994 TI - The role of fibre optics in gastroenterology. AB - Diagnostic fibre optic endoscopy has a well established role in clinical gastroenterology. The authors highlight the expanding therapeutic applications of this technology. PMID- 2270995 TI - The management of early skin cancer in the 90s. AB - Skin cancer has become a major source of illness and death in Australia. Recent advances in the early detection of skin cancer and in its treatment have significantly altered management, particularly of melanoma. Evidence that a high proportion of all skin cancers and most life-threatening skin cancers arise on the normally protected areas of the trunk and limbs has underlined the need for complete skin examination as a part of the care of long term patients in general practice. PMID- 2270996 TI - Tremors and shock waves. PMID- 2270997 TI - Dr Warwick Carter, medical writer. AB - As well as writing prolifically, the Brisbane doctor consults for 36 hours a week in his own practice and holds more than 20 seats on community, local government and AMA committees. He says the key is never to mix business with home. "Most of my income is generated not from general practice but from my other activities. Australian GPs are poorly paid. The government keeps telling people that GPs are ripping them off if they charge more than the medical rebate. The public's image of GPs is very low. The way it works now is that the more ethical you are and the more care you give to your patients, the less you earn." Warwick Carter does not known where his next challenge will lead him. He has three inflexible goals: to remain a GP, to finish his travels around the world, and not to volunteer for anything he does not enjoy. PMID- 2270998 TI - Women's knowledge of Papanicolaou smears. AB - In this survey women were questioned about their knowledge of Papanicolaou (Pap) smears. The findings demonstrate that women have a reasonably good general knowledge about Pap smears but a poor specific knowledge. These results have important public health implications and emphasise the need for greater communication between doctor and patient. PMID- 2270999 TI - Patient education. Hirsutism. PMID- 2271000 TI - Piriformis syndrome and buttock pain. PMID- 2271001 TI - Beginnings and endings. PMID- 2271002 TI - Use of dental broach for treatment of epistaxis. PMID- 2271003 TI - Carpal tunnel syndrome. PMID- 2271005 TI - Fitting a diaphragm. PMID- 2271004 TI - Recapping needles. PMID- 2271006 TI - Aminophylline activation of adrenaline mediated transmembrane K transfer in hyperkalemic dogs. AB - Ureter ligated control dogs that are K loaded by infusion with 2 mEq KCl/kg.h until prelethal electrocardiographic changes of hyperkalemic cardiotoxicity appear, transfer somewhat more than half the K load to intracellular fluid. The proportion is not significantly changed by adrenalectomy, but increased by treatment with aminophylline; the treatment has no effect on K transfer in adrenalectomized animals. Insulin is not involved; in dogs with adrenalectomy and pancreatectomy treatment with pharmacological dosages of adrenaline (Abbot), beta agonist activity is as effective as that with aminophylline. We conclude that aminophylline improves K transfer, by investifying beta agonist activity of endogenous adrenaline; it is known that increased beta agonist activity enhances beta receptor mediated K transfer in K loaded ureter ligated, intact and adrenalectomized dogs. PMID- 2271007 TI - Postnatal adaptation of lipase- and trypsin-activities in duodenal juice of premature infants appropriate for gestational age. AB - In 17 very low birth weight and in 13 low birth weight infants appropriate for gestational age the activities of pancreatic lipase and trypsin, the pH value and the concentrations of total bile acids were measured in the preprandially aspirated duodenal juice between the 10th and the 40th day of postnatal life. The activities of both enzymes increased significantly with increasing postnatal age in both study groups but did not correlate with the gestational age between the 28th and 33rd week of gestation. The pH values were on a low but similar level in both study groups (mean for all infants 5.66 +/- 0.07), and there was no influence of the pH value on the activities of either pancreatic enzyme. The concentrations of total bile acids were also not different between the study groups (mean for all infants = 4.55 +/- 2.26 mmol/l) and no correlation could be found between the concentrations of total bile acids and the activities of both measured enzymes. The data suggest that the intrauterine development of the exocrine pancreas reaches a basal level by the 28th week of gestation and remains on this level up to the 33rd week of gestation. After birth there is a significant increase in enzyme activities for both studied enzymes. PMID- 2271008 TI - Posttetanic long-term potentiation in the dentate gyrus of freely moving rats is accompanied by an increase in protein synthesis. AB - In rats, the incorporation of L-[U-14C]leucine into proteins of cytosolic (soluble proteins) and of the 100,000 x g pellet fraction from ipsilateral hippocampus subregions (CA1, CA3 and CA4/area dentata) and visual cortex was studied from 5 min to 65 min after electrical tetanization of the right perforant path. The rates of protein synthesis were estimated calculating the relative specific radioactivity of proteins (RSA). The stimulation parameters used were identical to those of previous experiments inducing post-tetanic long-term potentiation (LTP) of both the amplitude of population spike and the slope function of the excitatory post-synaptic potential (EPSP) in the area dentata. Under these conditions, RSA-values of both fractions evaluated in the CA4/area dentata were found to be about two times higher in tetanized rats compared to either stimulated or passive controls (p less than 0.05). In all the other brain regions studied, no differences between tetanized and control animals were observed. These results provided evidence for an LTP-induced augmentation of protein synthesis in the ipsilateral dentate area which might be an essential prerequisite for those structural changes realizing the long-lasting enhanced efficacy of synaptic transmission at the perforant path-granular cell connections within this hippocampus subfield. PMID- 2271009 TI - Effects of intraventricularly applied methylglucamine orotate on [3H] acetylglucosamine incorporation into rat brain tissue during a learning experiment. AB - The present work was undertaken to study the influence of intraventricularly applied methylglucamine orotate (MGO) at a memory-facilitating dose of 1 mumole vs. 1 mumole methylglucamine chloride (MGCl) as a control substance on the incorporation of intraventricularly injected [3H]acetylglucosamine into rat hippocampus and striatum plus thalamus. MGO or MGCl were applied 50 min prior to application of labelled aminosugar, the incorporation times being 1, 4 and 24 h. In non-trained animals, MGO produced an increased labelling of hippocampal proteins (20%) after 24 h, whereas labelling of the lipid fraction was virtually not altered. In trained animals (brightness discrimination model), the increase in labelling caused by MGO in hippocampal proteins was more marked (49%), and an even higher increase in labelling was noted for the hippocampal proteins was more marked (49%), and an even higher increase in labelling was noted for the hippocampal lipids (63%). The second brain region under investigation, striatum plus thalamus, showed no MGO-induced alterations in labelling. The findings are discussed in the light of the working hypothesis of the functional role of macromolecular changes occurring mainly in the hippocampus during memory formation. PMID- 2271010 TI - Antithrombin effects of native and recombinant hirudins. AB - Three recombinant variants of hirudin with the most evident difference in amino acid position 47 (Lys-47, Arg-47, Asn-47) were studied for their selectivity and affinity for the target enzyme thrombin in comparison to native hirudin. Native hirudin and the recombinant hirudins inhibit selectively the clotting enzyme thrombin. The affinity of native hirudin does not differ significantly from that of recombinant hirudin Lys-47 whereas a distinctly lower affinity for thrombin is found for recombinant hirudin Arg-47 and recombinant hirudin Asn-47. All hirudins investigated have the same potency to inhibit thrombin-induced coagulation. Changes in the affinity of hirudins for thrombin become evident from the inhibition of thrombin-induced platelet aggregation only. PMID- 2271011 TI - Effect of repeated application of nootropic drugs on sleep in rats. AB - The effects of repeated application of nootropic drugs on the sleep-wake cycle were investigated in rats. Piracetam, meclofenoxate and pyritinol were injected intraperitoneally, 100 mg/kg per day, during a period of 10 days. The sleep-wake cycle was recorded each day between 8 a.m. and 4 p.m. Repeated administration of piracetam and meclofenoxate led to an increase of the paradoxical sleep, a decrease of waking, and a very small increase of slow-wave sleep. Pyritinol, on the other hand, decreased the amount of paradoxical sleep. The paradoxical sleep latency was reduced by piracetam and meclofenoxate and enhanced by pyritinol, respectively. These findings and also previous results show that nootropic drugs have different effects on sleep, especially on paradoxical sleep. The possible relationship between sleep effects and memory effects of nootropic drugs and the usefulness of sleep studies for screening of nootropics are discussed. PMID- 2271012 TI - Comparative studies on the anticonvulsant effectiveness of nootropic drugs in kindled rats. AB - In an attempt to characterize the anticonvulsant efficacy of nootropics, their effect on different types of kindled seizures in rats has been studied. Nootropics in doses known to have protective effects in damaged brain functions possess anticonvulsant potency preferentially in pentylenetetrazole (PTZ)-kindled rats and generalized seizures. The most pronounced potency was seen in PTZ kindled rats, where all substances tested (piracetam, meclofenoxate, pyritinol, vinpocetine, methylglucamine orotate, naftidrofuryl) led to significant dose dependent anticonvulsant effects. In amygdala-kindled rats only vinpocetine, meclofenoxate and piracetam were effective. In neocortically kindled rats only vinpocetine and, to a smaller extent, pyritinol showed anticonvulsant effects. The data support the potential antiepileptic potency of nootropics. PMID- 2271013 TI - [Blood alcohol concentration is dependent on the sequence of the combined administration of trichlorethylene and ethanol]. AB - In equimolar amounts ethanol and trichloroethylene were administered intraperitoneally to male ICR mice in varying sequences. The sequence of administration proved to be decisive for the blood alcohol levels. In relation to ethanol alone following the simultaneous administration of trichloroethylene and ethanol the blood alcohol levels were elevated. This effect is furthermore enhanced if trichloroethylene was administered 1 h prior to ethanol administration. The reversed sequence had no effect on blood alcohol levels. PMID- 2271014 TI - In vitro effect of plasma during phenylhydrazine-induced erythrocyte oxidative damage. AB - Erythrocytes were incubated for 60 min either in plasma or phosphate-buffered saline containing 10 mM phenylhydrazine hydrochloride. Plasma prevented the decrease in membrane fluidity observed in saline-phenylhydrazine incubated erythrocytes but these cells showed decreases in both filterability and active extrusion of Na+ that were nearly 100% lower than those found in erythrocytes incubated in plasma-phenyl-hydrazine. Also erythrocyte lipid peroxidation, as measured as thiobarbituric acid reactive products, was 100% higher in the presence of plasma. These results suggest that plasma could play "in vivo" an active role during oxidant-induced erythrocyte damage, contributing significantly to the hemolytic effects of oxidation. PMID- 2271015 TI - Experimental autoimmune hepatitis: disease induction, time course and T-cell reactivity. AB - This study describes a murine model of autoimmune hepatitis: experimental autoimmune hepatitis. Experimental autoimmune hepatitis could be induced most effectively in male C57BL/6 mice by intraperitoneal immunization with the 100,000 g supernatant of syngeneic liver homogenate (S-100) in complete Freund's adjuvant. BALB/C and C3H mice were less susceptible than C57BL/6 mice. Experimental autoimmune hepatitis could not be induced in Lewis rats. Intraperitoneal immunization was more effective than intramuscular or subcutaneous injections, and the amount of protein administered above a threshold was of little influence. A single intraperitoneal injection of S-100 in complete Freund's adjuvant resulted in hepatitis of at least 6 mo duration. Histological changes were most marked 4 wk after disease induction. The histological findings were characterized mainly by perivascular inflammatory infiltrates and hepatocyte necroses. The histological changes were accompanied by biochemical evidence of liver cell death. Passive transfer of experimental autoimmune hepatitis with concanavalin A-activated splenocytes was possible. Specific T-cell reactivity against fractions of S-100 could be demonstrated in vitro. Thus experimental autoimmune hepatitis is a murine model of autoimmune hepatitis probably mediated by autoreactive T cells. It will allow studies of the pathogenesis of autoimmune hepatitis. PMID- 2271016 TI - Blindness and visual impairment in an American urban population. The Baltimore Eye Survey. AB - Data on the prevalence of blindness and visual impairment in multiracial urban populations of the United States are not readily available. The Baltimore Eye Survey was designed to address this lack of information and provide estimates of prevalence in age-race subgroups that had not been well studied in the past. A population-based sample of 5300 blacks and whites from east Baltimore, Md, received an ophthalmologic screening examination that included detailed visual acuity measurements. Blacks had, on average, a twofold excess prevalence of blindness and visual impairment than whites, irrespective of definition. Rates rose dramatically with age for all definitions of vision loss, but there was no difference in prevalence by sex. More than 50% of subjects improved their presenting vision after refractive correction, with 7.5% improving three or more lines. Rates in Baltimore are as high or higher than those reported from previous studies. National projections indicate that greater than 3 million persons are visually impaired, 890,000 of whom are bilaterally blind by US definitions. PMID- 2271017 TI - Rheumatoid arthritis. Pathophysiology and implications for therapy. PMID- 2271018 TI - Use of Veterans Administration outpatient facilities by older, rural veterans. AB - A mail survey was conducted in rural northeastern Missouri to study the factors affecting use of Veterans Administration (VA) outpatient medical services by older veterans. During the year preceding the survey, 39.6% of the 169 responding veterans had used VA outpatient facilities. Travel time, long waiting time at the clinic, and travel expense were the most common perceived barriers to use. However, these factors were generally poor predictors of use. The reported percentage of each perceived geographic or administrative barrier to use was consistently greater for previous users than for nonusers of these facilities. Multiple regression analysis revealed private medical insurance coverage to be the only significant predictor of use. Veterans with private medical insurance were more likely to receive ambulatory medical care from local providers than from the VA. The potential impact of removing perceived barriers to use in this population remains unclear. PMID- 2271019 TI - Methods used to quit smoking in the United States. Do cessation programs help? AB - Using data from the 1986 Adult Use of Tobacco Survey, we analyzed smoking cessation methods used by adult smokers in the United States who tried to quit. About 90% of successful quitters and 80% of unsuccessful quitters used individual methods of smoking cessation rather than organized programs. Most of these smokers who quit on their own used a "cold turkey" approach. Multivariate analysis showed that women, middle-aged persons, more educated persons, persons who had made more quit-smoking attempts, and, particularly, heavier smokers were most likely to use a cessation program. Daily cigarette consumption, however, did not predict whether persons would succeed or fail during their attempts to quit smoking. Rather, the cessation method used was the strongest predictor of success. Among smokers who had attempted cessation within the previous 10 years, 47.5% of persons who tried to quit on their own were successful whereas only 23.6% of persons who used cessation programs succeeded. We conclude that cessation programs serve a small, but important, population of smokers that includes heavier smokers, those most at risk for tobacco-related morbidity and mortality. PMID- 2271020 TI - Staff nurse turnover costs: Part II, Measurements and results. AB - This study demonstrated that the costs of nursing turnover can be high (over +10,000 per RN turnover), and that the potential for adverse impact on the nursing department, the hospital environment, and the healthcare environment exists. The results of this study are important, particularly in the midst of a national nursing shortage, for several reasons. CNEs are responsible for obtaining, allocating, and managing nursing department resources; knowledge of nursing turnover costs will allow them to make more informed decisions about how best to allocate scarce resources. The findings of this study are also important to hospital administrators because they demonstrate the financial impact of high rates of nursing turnover on healthcare delivery. Finally, these findings provide nurse researchers direction for future research into the costs and benefits of nursing turnover and retention activities, so that cost-effective methods of minimizing organizational costs can be determined. PMID- 2271021 TI - Superimposition of being: the collision of maternal and fetal rights. PMID- 2271022 TI - The disadvantages of helicopter transfer. PMID- 2271023 TI - Pre-eclampsia, dural tap and suxamethonium apnoea. PMID- 2271024 TI - Thiamine in our bread and wine? PMID- 2271025 TI - Long QT syndrome. New electrocardiographic characteristics. AB - The long QT syndrome is electrocardiographically characterized by a prolonged QT interval and by several other, more subtle, ST-T-U wave abnormalities, most of which have not been quantified. To determine the possible usefulness of several new electrocardiographic characteristics in identifying patients with known long QT syndrome, logistic regression models were applied to a data base of seven new, relatively independent, electrocardiographic repolarization variables. These were measured on digitized 12-lead electrocardiograms of 315 normal subjects and 37 patients with the long QT syndrome (members of well-identified long QT syndrome families, QTc greater than 0.44 second, 27% symptomatic), who ranged in age from 17 to 60 years. Electrocardiographic variables that independently differentiated (p less than 0.001) patients with long QT syndrome from normal subjects included quantitative measures of repolarization: early duration, rate, T wave symmetry, late phenomena, and heterogeneity. All selected repolarization variables except the early duration variable were essentially independent of the QTc (r2 less than 0.15), and all contributed significantly to the identification of patients with long QT syndrome. A classification model of five electrocardiographic predictor variables resulted in an estimated sensitivity (95% confidence interval) of 92.6% (81.6-100%) and an estimated specificity (95% confidence interval) of 95.8% (93.6 98.1%). This model performed significantly better than an alternative classification model that was based on the early duration variable as a single predictor variable. The symptomatic status of patients with long QT syndrome could not be predicted by any combination of the electrocardiographic variables in the investigated model. PMID- 2271026 TI - Lepromatous leprosy and dementia. PMID- 2271027 TI - Attitudes, knowledge and behaviour of general practitioners in relation to HIV infection and AIDS. Commonwealth AIDS Research Grant Committee Working Party. AB - A stratified random sample of 655 Australian general practitioners (GPs) was surveyed to determine their attitudes, knowledge and behaviour in relation to the human immunodeficiency virus (HIV) pandemic. Of the 486 respondents, 22% had one or more patients with HIV infection in their practice and 80% had been asked for information on HIV infection in the past month by at least one patient. The majority of respondents viewed screening and education of patients as part of their role, but 24% did not want to maintain a therapeutic relationship with HIV infected patients and 16% felt it was appropriate to refuse to treat this group. Although most respondents correctly identified the well known risk-taking behaviours for HIV infection in homosexual men and intravenous drug users, they underestimated the risk to heterosexuals and exaggerated that associated with activities generally considered not to involve risk. The knowledge of appropriate infection control procedures of approximately 60% of the respondents was inadequate. A lack of time in consulting was the most commonly cited barrier to the routine assessment of, or enquiry into, risk-taking behaviours of patients in the respondents' practices. Respondents noted that they required more knowledge of the clinical presentation and diagnosis of HIV infection, as well as education in counselling techniques and the risks of transmission associated with sexual and non-sexual activities. They felt such information could best be imparted through printed material. These results indicate that most GPs are willing to play an active role in the diagnosis, treatment and prevention of HIV disease, but they require more accurate information in order to fulfill this role appropriately. The study identifies and addresses several barriers to GPs playing a more active role in the management of HIV disease. PMID- 2271028 TI - Mortality in patients with bleeding peptic ulcer when those aged 60 or over are operated on early. PMID- 2271029 TI - Accidental drowning of toddlers in buckets. PMID- 2271030 TI - Tight scleral flap trabeculectomy with postoperative laser suture lysis. PMID- 2271031 TI - Unhappiness in medicine. PMID- 2271032 TI - Psychiatric illness in relatives of patients with bulimia nervosa. PMID- 2271033 TI - A patient's view of doctor-patient boundaries. PMID- 2271034 TI - Lead risks overlooked in sandblasters? PMID- 2271035 TI - On ambulatory care. PMID- 2271036 TI - Human papillomaviruses in anogenital warts in children. PMID- 2271037 TI - Scrotal calculi. PMID- 2271038 TI - Heterosexual AIDS: myth or epidemic? PMID- 2271039 TI - Hypoglycemia during diarrhea in childhood. PMID- 2271040 TI - Dehydration-induced oligohydramnios. PMID- 2271041 TI - Pemphigus in pregnancy. PMID- 2271042 TI - Normal amniotic pressure in oligohydramnios after preterm rupture of membranes. PMID- 2271043 TI - Mosaic pattern of dystrophin in DMD. PMID- 2271044 TI - 'The use of general anaesthesia for tooth extraction for child outpatients at a London dental hospital'. PMID- 2271045 TI - Lowering cholesterol concentrations and mortality. PMID- 2271046 TI - Hereditary (primary) haemochromatosis. PMID- 2271047 TI - Hints on tracheal intubation for non-anaesthetists. PMID- 2271048 TI - Surviving a crash landing: a software review. PMID- 2271049 TI - Megakaryocytopoiesis in patients with myelodysplastic syndromes (MDS) with and without del(5q) PMID- 2271050 TI - The evolution of a unit for the cognitively impaired elderly. AB - The MDE unit has filled a significant gap in the care of the psychogeriatric patient. Prior to its existence, the aggressive demented patient was generally managed by physical or chemical restraints. As community needs increase and require changes in the type of institutional care provided, the program will continue to respond with adaptive programs and expanded staff expertise. In the future the program may play a larger role. Due to gaps in the health care system, this type of program may have to admit more psychogeriatric patients. Also, this unique patient population could provide material for scientific research on dementia and its treatment. The MDE program depends not only on physicians and medications but also on a dedicated interdisciplinary team to manage this interesting and exceptional population. PMID- 2271051 TI - Psychiatric ward incidents. PMID- 2271052 TI - 4-quinolones and multivalent ions. PMID- 2271053 TI - Dihydroergotamine and intracranial pressure. PMID- 2271054 TI - Immunizations and medicolegal responsibilities. PMID- 2271055 TI - Is pseudotumor cerebri in SLE a thrombotic event? PMID- 2271056 TI - Mortality vs quality of life. PMID- 2271057 TI - The injecting and sexual behaviour of intravenous drug users. PMID- 2271058 TI - Semi-automatic focimetry. PMID- 2271060 TI - Tissue expansion for rhytidectomy. PMID- 2271059 TI - Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm. PMID- 2271061 TI - CT scan and facial fractures. PMID- 2271062 TI - The cellular basis of memory. AB - In the Perspective "Too many rodent carcinogens: Mitogenesis increases mutagenesis" by Bruce N. Ames and Lois Swirsky Gold (31 Aug., p. 970), the last paragraph on page 970 (continuing on page 971) was incorrectly printed. It should have read, "One major group of natural chemicals in the human diet are the chemicals that plants produce to defend themselves, the natural pesticides (4). We calculate that 99.9% (by weight) of the pesticides in our diet are natural. Few natural pesticides have been tested in at least one rodent species, and again about half (27/52) are rodent carcinogens. These 27 occur commonly in plant foods (10). The human diet contains thousands of natural pesticides, and we estimate that the average intake is about 1500 mg per person per day (4). This compares to a total of 0.09 mg per person per day of residues of about 100 synthetic pesticides (4). In addition, of the mold toxins tested at the MTD (induding aflatoxin), 11 out of 16 are rodent carcinogens." Also, in paragraph 3 on page 970, "47,000 8-hydroxydeoxyguanosines per cell" should have been "90,000" per cell. PMID- 2271063 TI - Lymphocytic bronchitis and lung allograft rejection. PMID- 2271064 TI - Zero tolerance. PMID- 2271065 TI - Contractural arachnodactyly versus Marfan's syndrome. PMID- 2271066 TI - Isolation and identification of the gene of cholesterol oxidase from Brevibacterium sterolicum ATCC 21387, a widely used enzyme in clinical analysis. AB - The gene coding cholesterol oxidase (CHOD) from Brevibacterium sterolicum, which is widely used in clinical analysis, has been selected from pUC19-based gene bank in E. coli MM294 by colony-hybridization using synthetic DNA as probe. The gene was identified to encode the protein having the same amino acid sequence as that determined from amino-acid sequence analysis. The expression of the CHOD gene in E. coli was not observed, probably due to the transcription failure. Attempts are being made to express it in various hosts including Streptomyces lividans, Corynebacterium glutamicum, and B. sterolicum itself. PMID- 2271067 TI - Occupational health nursing research. PMID- 2271068 TI - Occupational health nursing research. June 1984 to June 1989. AB - Nurses have multiple research reports related to occupational health published in a variety of scientific journals. Studies by occupational health nurses that adhere to the rigors of the research process are needed in all areas of occupational health. Use of nursing models by occupational health nurse researchers would contribute to a definite body of scientific knowledge to guide occupational health nursing practice. PMID- 2271069 TI - Interviewer bias. How it affects survey research. AB - Interviewing is a critical skill for the occupational health nurse when making clinical decisions as well as when conducting research; it allows the investigator to obtain information that would be difficult, if not impossible, to obtain by any other method. The personal qualities of the interviewer are key determinants of the outcome of the interview. Recognition of the potential for interviewer bias, attention to the characteristics of the respondents, and an analysis of the tasks required in the investigation will maximize the accuracy of the interview. Interviewer selection and training may be one of the most important tasks for the researcher. PMID- 2271070 TI - Effect of worksite health promotion programs on employee absenteeism. A comparative analysis. AB - Employee absenteeism is an important economic variable that needs to be examined by occupational health nurses when evaluating worksite health promotion programs. Two of the three Blue Cross and Blue Shield Plan studies suggested that their programs acted to contain absenteeism among program participants. The worksite programs that met with success tended to be comprehensive and to have strong management support. Strengths of the three studies included the use of comparison groups and pretest measures of absenteeism in the analyses. Limitations included selection bias, subject dropout over time, limited monitoring of the program process, and the use of an analysis method that did not consider the statistical characteristics of the absenteeism variable. PMID- 2271071 TI - Ethics and research. AB - Research subjects have the right to self-determination, informed consent, confidentiality and privacy, and freedom from harm. The use of coercion, such as a threat of harm, or excessive reward to influence subject participation in research is unethical. The benefits and risks related to participating in a research study should be disclosed to all subjects. In order to conduct the study, the benefits should exceed the risks. PMID- 2271072 TI - Managing change. PMID- 2271073 TI - Optical resolution of benzodiazepine esters by HPLC. AB - The separation of the enantiomers of 11-26 esters of oxazepam 1, temazepam 2, lorazepam 3 and lormetazepam 4 whith the acids benzoic 6, 2-methyl-3-nitrobenzoic 7, cynnamic 8 and hydrocynnamic 9 by HPLC on analytical columns with chiral stationary phases of (R)-N-(3,5-dinitrobenzoyl)phenylglycine (R)-DNBPG and (S)-N (3,5-dinitrobenzoyl)leucine (S)-DNBL was described. The diastereoisomeric mixtures of esters 27-30 of the overmentioned benzodiazepines with (S)(+)-2-(6 methoxy-2-naphthyl)propionic acid have been also separated by HPLC on analytical column of SiO2. Some of the best separations have been repeated on semipreparative scale in order to isolate and characterize the optically pure enantiomers or diastereoisomers. Configurational assignment and elution order are established by a chiral recognition model. On the basis of the study by molecular models of the interaction between solute and chiral stationary phases, the conformers more interacting with these phases have been individuated and it has been possible to conclude that for any enantiomers couple the (S) isomer is always more retained by the chiral stationary phase of (R)-DNBPG and the (R) isomer by (S)-DNBL. Regarding to the interaction of diastereoisomeric esters 27 30 with SiO2, the esters more retained should result those of the benzodiazepines having (S) configuration. PMID- 2271074 TI - 7-Substituted theophyllines. Part VI--N-[2-(4-chlorophenoxy)-1-phenyl-alkyl] alkylamido derivatives. AB - The new amides are inhibitors of cholesterol biosynthesis in vitro as well as in vivo. These compounds are also inhibitors in vivo of triglyceride biosynthesis and of platelet aggregation. All tests showed activity (values expressed as percentage variation) much greater than clofibrate. Besides, all compounds have no effect on coagulation or diuresis and showed low acute toxicity. PMID- 2271075 TI - Spectrophotometric determination of bismuth in pharmaceutical preparations using 1-[di(2-pyridyl)--methylene]-5-salicylidene-thiocarbonohydrazide. AB - A simple and fast spectrophotometric method for the determination of bismuth in pharmaceutical preparations is described. The used chromatic reactive is 1-[di(2 pyridyl)methylene]-5-salicilydene-thiocarbonohydrazide+ ++ forming a yellow complex with bismuth. In a solution containing 40% v/v of dimethylformamide molar absorption is 5.7 x 10(4) l.mol-1.cm-1 at 421 nm and at pH 4.3. The optimal conditions for the color development and the possible interferences are studied. PMID- 2271077 TI - Ostomy teaching protocol. PMID- 2271076 TI - Determination of salicilic acid in saliva by high-performance liquid chromatography. AB - A sensitive reversed-phase HPLC method with fluorimetric detection was developed for the determination of salicilic acid in saliva samples. The method, involving a preliminary solid-phase extraction procedure, was found to be suitable for the determination of salivary salicilic acid concentrations following the administration of a single oral dose of some commercial acetylsalicilic acid formulations. PMID- 2271078 TI - Developing a research approach for the treatment of pressure ulcers. PMID- 2271079 TI - The comparative efficacy and safety of 5% povidone-iodine cream for topical antisepsis. AB - A 5% povidone-iodine cream (Betadine Cream, The Purdue Frederick Company, Norwalk, Conn.) was tested extensively to determine its safety and efficacy. Results of in vitro microbiologic comparison found that a representative panel of vegetative test organisms couldn't be recovered after 60 seconds or less exposure to povidone-iodine (PVP-I) cream, whereas the kill time of the combination antibiotic cream (Neosporin Cream, Burroughs Wellcome, Research Triangle Park, NC) exceeded 15 minutes for at least half of vegetative organisms. PVP-I cream produced a log reduction of Bacillus pumilis spores after less than one hour's exposure; the antibiotic cream did not. Both PVP-I and antibiotic creams were essentially non-irritating in human and in vivo animal studies. In open wounds, 5% PVP-I cream caused little or no burning and pain upon application. In human comparisons, artificially induced, standardized lesions inoculated with Staphylococcus aureus, were treated twice daily with PVP-I cream or triple antibiotic ointment (Neosporin Ointment, Burroughs Wellcome, Research Triangle Park, NC) over three weeks. Both caused significantly reduced bacterial counts (p less than 0.001), and significantly faster healing (p less than 0.05) than no treatment. PMID- 2271080 TI - Continent Indiana reservoir: nursing management. PMID- 2271081 TI - The management of open wounds: acute and chronic. AB - The history of wound healing dates back thousands of years before Christ to the Ancient Egyptians. Detailed tomb and temple hieroglyphics depict wound treatments of that era. Through the historic milestones set forth by Hippocrates (400 BC) to Lister (1800s), current theory of wound management and trends have evolved. During the last several decades, thanks to breakthroughs in research and technological advances, wound care has taken a giant leap forward. PMID- 2271082 TI - Generic equivalents that aren't... PMID- 2271083 TI - Renal allograft immunosuppression. II. A randomized trial of withdrawal of one drug in triple drug immunosuppression. AB - A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n = 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D--81%, 88%, 88%, and 88%, respectively--or in patient survival--88%, 88%, 88%, and 97%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271084 TI - Postoperative recovery of mitochondrial function of the human liver graft procured and preserved with University of Wisconsin (UW) solution. AB - Changes in arterial blood ketone body ratio (KBR) were investigated in 47 human liver transplantations. Of the 20 grafts preserved with University of Wisconsin (UW) solution, 10 had a cold preservation period of less than 10 h (UWS group) and 10 of more than 10 h (UWL group). In 27 other cases, grafts were preserved with EuroCollins (EC) solution for less than 10 h (EC group). In the EC group, KBR increased over 0.7 within 6 h after reperfusion of the graft in 17 cases (63%) and within 24 h in 7 cases (26%). In the 3 other cases, KBR failed to recover, and these patients underwent retransplantation. In the UW group, KBR recovered within 6 h in 13 cases (65%) and within 24 h in 7 cases (35%). There were no significant differences between the UWS and UWL groups. It is shown that the mitochondrial function of liver grafts preserved with UW solution can be well maintained even after extended preservation periods of more than 10 h. PMID- 2271085 TI - Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model. AB - The Eurocollins (EC) and University of Wisconsin (UW) preservation solutions were compared in a rat liver transplant model. After hepatectomy, 48 rat livers were flushed with either EC or UW preservation solution and were randomly assigned to 1, 12, 24, and 30 h of preservation at 4 degrees C, resulting in eight groups each containing six livers. Following preservation, orthotopic liver transplantation with reconstruction of the hepatic artery was performed. The efficacy of the preservation solution was assessed at 48 h post-transplantation by survival histological features and aspartate transaminase assay (AST) values. None of the rats survived 30 h of liver preservation with EC whereas five out of six rats did with UW preservation. After 24 h of liver preservation, three of the six rats in the EC group survived, compared to all six rats in the UW group. Histological evidence of severe ischemia was found in both groups in all but one survivor (UW, 24 h). After 12 h of EC preservation, one rat died within 48 h and severe ischemic changes were found in the remaining five rats. Among the rats with 12 h of UW preservation, only two out of six showed ischemic changes, and all six rats survived beyond 48 h. Without preservation (1 h), ischemic damage was found in two out of six rats in each group and all rats survived. The median AST values were higher in the EC groups than in the UW groups; the difference became significant after 12-h preservation (EC 900 IU/l versus UW 465 IU/l) and 24-h preservation (EC 5220 IU/l versus UW 631 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271086 TI - Stenting of the ureterovesical anastomosis in pediatric renal transplantation. AB - From January 1985 to July 1989, 36 children received a renal transplant at our hospital. Their ages ranged from 2 to 18 years. All patients had a standard neoureterocystostomy according to Lich-Gregoir. In the first 18 patients, no transanastomotic stent was placed. In the latter 18, a transanastomotic stent with or without suprapubic bladder drainage was performed. In the nonstented group, six severe urological complications occurred, two of which eventually resulted in loss of the transplant. In the stented group, only one severe urological complication occurred. No kidneys in this group were lost due to urological complications. The number of urinary tract infections in the nonstented group was the same as in the stented group. PMID- 2271087 TI - Evaluation of temporary portal vein arterialization: the minimum arterialized blood flow for maintaining liver viability. AB - The effect of temporary portal vein arterialization (PVA) on hepatic energy metabolism was investigated by changes in the arterial blood ketone body ratio (KBR) and hepatic energy charge (EC) level in 17 dogs. The KBR decreased markedly after clamping the hepatic hilar vessels combining mesocaval shunt and remained at a low level throughout hepatic ischemia. After PVA, the KBR was rapidly restored and maintained at sufficient levels. EC at 60 min after arterialization also recovered to the preclamping level. By reducing the arterial shunt flow, the critical point of arterialized blood flow for maintaining the KBR at high levels was assessed to be about 10% of the total hepatic blood flow (THBF). These findings demonstrate that temporary PVA is an effective method for maintaining the functional capacity of the liver, and that the minimum arterialized blood flow needed to preserve liver viability is only about 10% of the total hepatic blood flow. PMID- 2271088 TI - Does combined kidney and pancreas transplantation reverse functional diabetic microangiopathy? AB - Using videophotometric capillaroscopy and laser Doppler fluxmetry, we have investigated skin microvascular reactivity in the fingers of 14 diabetic patients with severe, late complications 20 months after combined kidney and pancreas transplantation. The results were compared with those obtained in 20 diabetic patients awaiting pancreas transplantation and in 19 healthy subjects. The capillary blood cell velocity at rest (P less than 0.01) and during postocclusive reactive hyperemia (P less than 0.05) was significantly lower in both patient groups than in the healthy controls. However, the time to peak capillary blood cell velocity during hyperemia was normal in the post-transplantation group (NS) but significantly prolonged in the pretransplantation group (P less than 0.01). The ability to decrease flow during venous stasis-the so called venoarte-riolar reflex--was strongly impaired in the pretransplantation group (P less than 0.001) but less so in the post-transplantation group (P less than 0.05) as compared to healthy controls. It may be concluded that diabetic patients, after combined kidney and pancreas transplantation, show a tendency towards better microvascular reactivity than those awaiting transplantation. PMID- 2271089 TI - Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients. AB - The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125I-iothalamate and 131I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re - and EPA - re -. These two groups were comparable in age, donor age, and GFR. The EPA + re-group had a significantly lower ERPF (164 ml/min per 1.73 m2) than the EPA-re- group (262 ml/min per 1.73 m2). FF was significantly higher in the EPA+ re-group (0.26) than in the EPA-re-group (0.21).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271090 TI - Immune repertoire of graft-invading T cells. AB - The immune repertoire of T lymphocytes invading human allografts is of fundamental importance both at the operational level, in order to achieve relevant matching, and at the functional level, since the unique capacity of T and B cells to specifically recognize allogeneic components restricts the origin of the signals leading to rejection by these cells. In this paper, the authors review their own work, as well as other contributions in this domain, with special reference to the frequency and function of donor-committed cells among the infiltrate and the relationship between T-cell receptor gene rearrangements and repertoire. PMID- 2271091 TI - A technique of pancreas transplantation in the rat securing pancreatic juice for monitoring. AB - In order to study exocrine pancreas graft function and cytological findings, a technique of vascularized pancreas transplantation with special reference to a pancreatic juice collecting system has been developed in the rat model. For this purpose, a catheter is introduced into the common bile duct, which is ligated close to the duodenum, thus covering all pancreatic ducts. This catheter is connected to a reservoir implanted subcutaneously, from which pancreatic juice can easily be aspirated. The amount of 0.7-1.2 cc of juice produced over a 24-h period has proven to be sufficient for various analyses and cytological examination. PMID- 2271092 TI - Two approaches to health promotion in the mass media. AB - This article concentrates on two strategies for health promotion in the mass media: social marketing aims to influence people's behaviour, media advocacy to influence their environment. The author argues that greater weight should be given to media advocacy than to social marketing so as to achieve an improved understanding of the conditions required for health. PMID- 2271093 TI - Community participation boosts immunization coverage. PMID- 2271094 TI - Financial inducement for improving the efficacy of immunization. PMID- 2271095 TI - The ethics of prenatal diagnosis and genetic counselling. AB - Doctors are often censured for the aborting of severely abnormal fetuses after prenatal diagnosis. But, where parents have been left in ignorance and have produced an abnormal child, there has been a very strong sense of injustice. The moral responsibility must ultimately rest with the parents, who must have control of their own health and that of their families. PMID- 2271096 TI - Light on maternal mortality in India. AB - In order to investigate the degree and causes of maternal mortality in Anantapur District, Andhra Pradesh, India, detailed enquiries were made at the grass roots and the records of health facilities were examined. The number of maternal deaths proved to be much higher than would have been revealed by a perusal of official data alone. Many women in a serious condition died on the way to hospital or soon after arrival because the means of transport were too slow or otherwise unsuitable. Maternal mortality rates varied substantially from place to place, reflecting differing levels of economic development and the presence or absence of primary health centres and subcentres. PMID- 2271097 TI - Integration of traditional birth attendants into primary health care. AB - An evaluation of domiciliary midwifery services in a suburban area of Benin City, Nigeria, revealed that mothers liked them mainly because of the provision for home delivery. The integration of traditional birth attendants into organized health care was considered desirable by both mothers and the midwifery staff. Domiciliary midwifery services are recommended as a means of integrating traditional birth attendants into primary health care. PMID- 2271098 TI - Children with AIDS. PMID- 2271099 TI - Mongolia's successful immunization programme. PMID- 2271100 TI - First European study using cold chain monitors. PMID- 2271101 TI - First aid in the era of primary health care. PMID- 2271102 TI - Health cards help to gain workers' participation in occupational health surveillance. PMID- 2271103 TI - Blood tests and oral contraception. PMID- 2271104 TI - More community obstetricians are needed. PMID- 2271105 TI - Nutrition monitoring by village health workers. PMID- 2271106 TI - Teaching the value of water in disease control. PMID- 2271107 TI - Ethics in health systems research. PMID- 2271108 TI - Women, children and AIDS. PMID- 2271109 TI - Supplementation of breastfeeding infants and weight loss in hospital. AB - Charts were reviewed to determine the frequency of glucose water supplementation of breastfed babies during their hospital stay and to discover if glucose water supplementation affected weight loss. Babies who received glucose water supplementation lost more weight and stayed in hospital longer than babies who did not receive supplementation. These findings were statistically significant. Routine supplementation with glucose water is unnecessary and potentially harmful to the baby. Stopping this practice may increase the mother's milk supply, increase her confidence in the adequacy of her supply and decrease the length of hospital stay. PMID- 2271110 TI - Helping adults learn. AB - Effective teaching requires an understanding of what goes on inside the learner. Adults possess life experience and a concept of themselves which affect their capacity to learn. Adult learners want to be actively involved in their learning experiences and expect them to be relevant and useful. Significant learning, through its cognitive, affective, and behavioral dimensions, engages the whole person. People perceive and process data in different ways and through different stimuli. In order to develop courses that maximize people's natural learning processes, lactation consultants need to be aware of the assumptions, expectations, and varied learning styles new mothers bring. Breastfeeding educational programs which encourage active participation, self-direction and interdependence, which respect mothers' own experiences, and which appeal to a range of learning styles are more likely to encourage risk-taking, open sharing, and trying new behaviors which in turn result in lasting learning. PMID- 2271111 TI - Subtle signs and symptoms of the milk ejection reflex. PMID- 2271112 TI - Gentian violet treatment for thrush: can its use cause breastfeeding problems? PMID- 2271113 TI - A different concept in CEU delivery. PMID- 2271114 TI - Radiopharmaceuticals and lactation. PMID- 2271116 TI - Time was... The Canadian Mother's Book. Le Livre des Meres Canadiennes. 1936. PMID- 2271115 TI - Guidelines for the establishment and operation of a human milk bank. PMID- 2271117 TI - Radiotherapy QA--a systematic approach. PMID- 2271118 TI - Implementing a radiological information system in a diagnostic department. PMID- 2271119 TI - A method of practically assessing students in diagnostic radiography. AB - In the past, results of practical assessments were affected by their subjectivity. The objective assessment described here allows more accurate observations to be made and, while not without problems, has given favourable results. PMID- 2271120 TI - Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation. AB - The G0S19 genes are members of the "small inducible" family of genes, which have similar exon-intron organizations and encode secreted proteins with similar dispositions of cysteine and proline residues. G0S19-1 mRNA is increased shortly after the addition of lectin or cycloheximide to cultured human blood mononuclear cells. The cDNA sequence is homologous to that of a murine gene encoding an inhibitory cytokine (MIP1 alpha/SCI), which decreases hemopoietic stem cell proliferation. The homology extends to the 3' noncoding region, which contains two conserved elements: (i) GGGACTCTTC, a potential transcription factor NF chi B binding site, and (ii) TTTTGTAATTTATTTT, which is found in some related genes (e.g., that encoding the immediate early protein ornithine decarboxylase). A similar but complementary sequence is present in human immunodeficiency virus. Two of the three human genes that hybridize to G0S19-1 cDNA were sequenced. G0S19 1 has 5' AP1-like recognition elements as found in some other phorbol ester responsive genes (e.g., c-fos). G0S19-2 has a 5' Alu sequence, but is likely to be expressed because of the conservation of sections of the gene believed to be important for function. The 5' flanks of both genes contain the nucleotide motifs CK-2 and SRE, indicating cytokine-like genes with the potential to respond to growth factors. G0S19-1 is the main G0S19 gene expressed in adult T lymphocytes and may encode a homeostatic negative regulator of the size of cell populations (or subpopulations) which are derived ultimately from marrow stem cells. As such, it is a potential antioncogene. PMID- 2271121 TI - Electroporation of adherent cells in situ. AB - A simple, rapid, and reproducible procedure for the introduction of macromolecules into adherent mammalian cells by electroporation is described. Cells were growing on a glass surface coated with electrically conductive, optically transparent indium-tin oxide at the time of pulse delivery. Several factors affected the optimal voltage for permeation of a given line including the metabolic state of the cells and their degree of spreading onto the conductive growth surface. Careful control of the electric field strength resulted in almost 100% of the cells containing introduced antibodies without any detectable change in the length of their division cycle. Higher voltages were required for the stable expression of DNA than for the introduction of antibodies, resulting in a significant rate of cell death. PMID- 2271122 TI - [Clinical application of echocardiography in children]. AB - Biplane echocardiography is an important diagnostic resource in the management of infants with congenital heart disease and severe symptoms. It is also an useful method in the ambulatory assessment of children of any age suspected of having a congenital or acquired heart lesion. At the Hospital Infantil de Mexico Federico Gomez, echocardiography has substituted cardiac catheterization studies in the pre-operative diagnosis of several lesions, including many with a high degree of anatomic complexity, without incurring in the morbidity and high costs of invasive techniques. PMID- 2271123 TI - [Histocompatibility antigens and acute vascular purpura]. AB - INTRODUCTION: Some kidney diseases are associated to HLA antigens. Nyulassy found an increase in HLA-B35 in patients with Henoch-Schonlein's purpura suffering nephritis (HSP-N). Our study searched for associations of HLA antigens and anaphylactoid purpura nephritis in Mexican mestizo patients. MATERIAL AND METHODS: HLA-A,B, and C antigens were detected by two-step microcytotoxicity in 22 patients with HSP-N and compared to those of 665 healthy subjects of the same ethnic background. RESULTS: A significant association was found between HSP-N and HLA-Aw19 single (pc less than 0.05) or in haplotype form (Aw19-B35) (pc less than 0.005). HLA B35 alone was associated to HSP-N but only at non corrected level (pc less than 0.05). DISCUSSION: The significant association between HLA-Aw19 and Aw19-B35 and HSP-N may indicate a risk factor in Mexican mestizo patients to develop this case. PMID- 2271124 TI - [Acute intrathoracic respiratory infections in hospitalized children. Uruguay 1984-1986]. AB - Between may 1984 and november 1986, a study, which included 475 children under five years of age hospitalized due to acute intrathoracic respiratory infections, was carried out in order to obtain clinical, radiological and etiological characteristics which may aid in establishing norms to diagnose and treat these patients. Nasopharyngeal aspirations were performed on each child, while viral diagnosis was done through viral isolation techniques and indirect immunofluorescence. The presence of a virus was detected in 34.4% of the cases and in 28.8% of a subsample. A precoded questionnaire was used to obtain the clinical information needed and all X-rays were reviewed by the same radiologist using simple pre-established criteria. A comparison was made on the similarities found between both the clinical and radiological diagnosis, as well as the sensitivity and specificity of some of the clinical signs which characterize bronchiolitis and the pneumoniae. PMID- 2271125 TI - [Comparative study of 2 oral rehydration solutions containing 60 or 90 mmol/L of sodium and with different osmolalities]. AB - A total of 186 infants, suffering from acute diarrhea were studied and divided into two groups: 84 children were placed in group A and given the ORS recommended by the World Health Organization which contains sodium and glucose at concentrations of 60 and 90 mmol/L respectively and an osmolality of 311 mOsm/kg (mmol/kg) (ORS-90). Group B included 82 children who received an ORS containing sodium and glucose at concentrations of 60 and 90 mmol/L respectively and with an osmolality of 240 mOsm/kg (mmol/kg) (ORS-60). Seven belonging to group A (8.3%) required intravenous rehydration due to the severity of the diarrhea (three cases), persistent vomiting (three cases) and paralytic ileus (one case), while only two cases belonging to group B (2.5%) required intravenous rehydration due to severe losses through feces (one case) and another due to paralytic ileus (one case). No differences were observed due to the variations in sodium concentrations among either of the groups of patients, whether that be in the natremias when admitted or once rehydrated, with a general tendency towards the correction of the hypernatremia or hyponatremia seen during admittance with both types of ORS. A similar situation was observed with the variations in serum potassium. The results obtained from this study show the different advantages of using an ORS with lesser sodium and glucose concentrations as well as minor osmolality with those from using the solution recommended by the World Health Organization, when a lesser index of failures is observed in the treatment of children with acute diarrhea with oral rehydration therapy. Yet before widely recommending its' use, it should be demonstrated that the new ORS induces lesser losses through feces during the rehydrating period in children dehydrated due to acute diarrhea. PMID- 2271126 TI - [Susceptibility to measles in the adolescent population of the Federal District]. AB - It is well known that in developing countries, measles disease is frequently increasing among adolescents. In Mexico, it is also thought that this problem is moving in such a way; however, this can not be proven with the statistical information at hand. For this reason a serum-survey was carried out in a sample of 870 healthy teenagers drawn from public and private secondary schools in Mexico City, in order to know if they were susceptible to measles disease and in that way make the right decisions. The information background related to the vaccination and information about previously having the disease was obtained from a questionnaire that was given to the parents of the studied teenagers. In order to get de immune state of the studied group, measles antibody titles were quantified using the ELISA technique. The findings shown that the susceptibility in this group was of 21.4%, which is certainly higher than the ones that have been found in some other countries where measles epidemics in people at this age have been well documented. Accordingly, it is thought that the displacing of this illness can be found in teenagers of Mexico City. An association was found with male sex and having the illness before. Teenagers that studied in public secondary schools reported more frequently, they had had the illness than the ones who studied at private schools. It was also found that these teenagers had a higher probability of having antimeasles antibody titles which are considered non protective; that is why it is thought these students are more likely to become ill during the adolescence stage than those who already have had the illness and the consequent protection. PMID- 2271127 TI - [Traumatism of the posterior fossa in children]. AB - Reported are 15 cases of children who suffered injuries to their posterior fossa and the subsequent formation of hematomas and their treatment by the physicians in the Neurosurgical Department of the Traumatology Hospital "Magdalena de las Salinas". Of the 15 cases, 11 had epidural hematomas (three of them with supratentorial extensions), one was subdural, two were cerebellar and another of the brainstem. Seven were considered acute, five were subacute and three were chronic. During their admittance to the hospital, five of the patients were in a state of coma, another five were sleepy or confused and the remaining five were conscious. Three of the patients were conservatively treated, two of which had sequelae or were moderately handicapped. Twelve of the patients were surgically intervened suboccipitally, eleven of which successfully recovered and one of which died. A history of brain injury, occipital fracture and signs of posterior fossa lesions lead to suspect the presence of posterior fossa hematoma. PMID- 2271128 TI - [Recurrent complete rectal prolapse as a complication of posterior perineostomy, cured with posterior sagittal ano-rectoplasty]. AB - Among the anal-rectal malformations seen in females, the vestibular fistulae is frequently underestimated and tried to be corrected with a simple posterior perineostomy which may eventually cause, besides a esthetic problems, anatomical and physiological irregularities as those seen in a three year old girl, who after a posterior perineostomy for a vestibular fistula, suffered a complete recurrent rectal prolapse, which was intended to be corrected after eight unsuccessful surgical interventions. Finally, the child was cured after a posterior sagittal ano-rectoplasty. After a two year follow-up, the child has not had another rectal prolapse. PMID- 2271129 TI - [Effect of gene dosage on the glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPD) in partial 12p13.3 pter trisomy]. AB - A family with three brothers presenting 12p trisomy due to an adjacent-1 segregation of a paternal translocation (1;12) (q44;p12.2) is described. The patient's phenotype was compatible with the chromosomal imbalance including the gene dosage effect of the glyceraldehyde-3-phosphate dehydrogenase. The importance of the genetic counseling in these families is stressed. PMID- 2271130 TI - [The pediatrician and epidemiology]. AB - Pediatrics and epidemiology are two specialties of medicine with independent training. The pediatrician is trained in a clinical setting with practice and theoretical knowledge throughout several years in an accredited hospital, whereas the epidemiologist is trained in a more theoretical basis with field works as its practice. Nevertheless, the pediatrician constantly uses the epidemiological method although he or she may not be aware of this. The purpose of this paper is to explain in a very short way, the relationship between both disciplines. Aspects of descriptive, analytic and experimental epidemiology are given. PMID- 2271131 TI - [Water-electrolyte and acid-base imbalance. IX. Respiratory alkalosis]. AB - Respiratory alkalosis is the consequence of primary hypocapnia of divergent etiologies. Any pathologic process that increases ventilation to levels beyond that required to excrete the CO2 byproduct of metabolism, will result in an inappropriately low systemic pCO2 and a tendency to an alkaline systemic pH. The increased drive to ventilation may be due predominantly to a primary increase in central nervous system activity, either within the respiratory center itself or from more centrally placed areas with neural projections that extend to and control the respiratory center. Alternatively, an increased drive to ventilation may result from an "appropriate" physiologic response to another more important stimulus that overrides the human's needs to protect pCO2 and pH. Hypoxia (of different causes), is the most important and most commonly encountered such stimulus. PMID- 2271132 TI - CPA/Niccol lecture. Changing the image of retirement. PMID- 2271133 TI - Marrying age and services. PMID- 2271134 TI - Setting the scene. PMID- 2271136 TI - Aided independence from A to Z. PMID- 2271135 TI - Design for living. Exhibiting choice. PMID- 2271137 TI - Hypothermia. The threat of a cold environment. PMID- 2271138 TI - Hope for the hopeless. PMID- 2271139 TI - Responsible discharges. PMID- 2271140 TI - As I was saying. PMID- 2271141 TI - Voluntary organisations. Growing old in Kenya. PMID- 2271142 TI - Voluntary organisations. A sound base. PMID- 2271143 TI - Buzz phrase of the year. PMID- 2271144 TI - Use of language. Entitled to respect. PMID- 2271145 TI - Fish scales as biosensors for catecholamines. AB - Certain fish scales contain specialized cells (chromatophores) with pigment granulas, which can be dispersed or aggregated in the cells. The degree of aggregation is determined by a transmitter substance, noradrenaline, released by the sympathetic nerve endings in the skin. Isolated scales from, for example, cuckoo wrasse (Labrus ossifagus) retain a large sensitivity to externally applied noradrenaline (or more generally catecholamines) for several weeks. The degree of aggregation in isolated scales can be measured objectively by simple photometric techniques. We demonstrate in this paper how fish scales can be used to monitor catecholamine levels in human blood plasma. A discussion of other potential biosensor applications of this intact biological receptor-effector system is also given. PMID- 2271146 TI - Studies on acetylcholine sensor and its analytical application based on the inhibition of cholinesterase. AB - Acetylcholine esterase electrodes, based on glass, Pd/PdO and Ir/IrO2 electrodes as pH sensor, using the immobilized acetylcholine esterase in acrylamide methacrylamide hydrazides prepolymer are reported and compared. New data on the analysis of nicotine, fluoride ion, and some organophosphorus compounds are reported using the present AChE sensor based on the inhibition of the immobilized acetylcholine esterase. Reactivation of immobilized AChE after inhibition with reversible inhibitor, i.e. nicotine and fluoride ion is carried out using a mixture of working buffer and acetylcholine, whereas reactivation after inhibition with irreversible inhibitor, i.e. organophosphorus compounds is carried out using a mixture of acetylcholine and pyridine-2-aldoxime methiodide (PAM). The detection limits for the nicotine and fluoride ion are found to be 10( 5) M whereas for paraoxon, methyl parathion and malathion are found to be 10(-9) M and 10(-10) M. PMID- 2271147 TI - Optimization of a polypyrrole glucose oxidase biosensor. AB - An amperometric glucose biosensor was fabricated by the electrochemical polymerization of pyrrole onto a platinum electrode in the presence of the enzyme glucose oxidase in a KCl solution at a potential of +0.65 V versus SCE. The enzyme was entrapped into the polypyrrole film during the electropolymerization process. Glucose responses were measured by potentiostating the enzyme electrode at a potential of +0.7 V versus SCE in order to oxidize the hydrogen generated by the oxidation of glucose by the enzyme in the presence of oxygen. Experiments were performed to determine the optimal conditions of the polypyrrole glucose oxidase film preparation (pyrrole and glucose oxidase concentrations in the plating solution) and the response to glucose from such electrodes was evaluated as a function of film thickness, pH and temperature. It was found that a concentration of 0.3 M pyrrole in the presence of 65 U/ml of glucose oxidase in 0.01 M KCl were the optimal parameters for the fabrication of the biosensor. The optimal response was obtained for a film thickness of 0.17 microns (75 mC/cm2) at pH 6 and at a temperature of 313 K. The temperature dependence of the amperometric response indicated an activation energy of 41 kJ/mole. The linearity of the enzyme electrode response ranged from 1.0 mM to 7.5 mM glucose and kinetic parameters determined for the optimized biosensors were 33.4 mM for the Km and 7.2 microA for the Imax. It was demonstrated that the internal diffusion of hydrogen peroxide through the polypyrrole layer to the platinum surface was the main limiting factor controlling the magnitude of the response of the biosensor to glucose. The response was directly related to the enzyme loading in the polypyrrole film. The shelf life and the operational stability of the optimized biosensor exceed 500 days and 175 assays, respectively. The substrate specificity of the entrapped glucose oxidase was not altered by the immobilization procedure. PMID- 2271148 TI - Evaluation of neuron-based sensing with the neurotransmitter serotonin. AB - Results are presented on the development of a novel biosensor which will use neurons or neuronal components as both the recognition elements and primary transducers for analyte quantitation. This concept is demonstrated and evaluated by exposing identified neurons from the visceral ganglia of the pond snail Limnea stagnalis to the model analyte serotonin. Experiments reveal a reversible, concentration-dependent increase in the rate of spontaneous action potential generation, over a concentration range of four orders of magnitude. Studies with the antagonist methysergide verify that this response is mediated through serotonin-sensitive receptors. Exposure of the neurons to serotonin causes the firing frequency to rapidly increase to a maximum and then slowly diminish to a sub-optimal level. It was found that the maximum frequency provides an indication of chemical concentration that is repeatable. Data are also presented which further advance the field of neuronal biosensing by demonstrating both the effects of cell to cell variability on response reproducibility and the effects of the desensitizing response on the operation of a neuron-based sensor in both a continuous and discontinuous mode. PMID- 2271149 TI - ASEPSIS. The infection control forum: where do we go from here? PMID- 2271150 TI - Call from the renal transplant unit. PMID- 2271151 TI - Critical care medicine: activities, advances, and implications for infection control. PMID- 2271152 TI - Critical care medicine: activities, advances, and implications for infection control. PMID- 2271153 TI - Fourier analysis of the relation between the discharge of quadriceps motor units and periodic mechanical stimulation of cat knee joint receptors. AB - It has been widely assumed that joint receptors contribute to the reflex regulation of movement and posture, although there have been few clear demonstrations of joint-mediated reflex actions on alpha-motoneurones other than those attributable to flexor reflex afferents. The present study extends our recent work on joint-mediated reflexes by using Fourier analysis of spike train interactions to demonstrate that restricted mechanical activation of a small number (one to five) of knee joint receptors by localized indentation of the joint capsule can modify the firing pattern of quadriceps motoneurones in decerebrated cats. The modulation of this discharge pattern can be reversibly abolished by application of droplets of lignocaine directly to the joint nerve and consequently can be attributed unambiguously to articular afferents. Activation of single joint afferents could on occasion produce changes in motor unit firing patterns, but usually activation of two or more was required before secure effects were observed. Increasing the intensity of indentation (resulting in activation of greater numbers of joint receptors) increases the strength of coupling between joint afferent input and motor unit responses, although the relationship is not linear. The relation between the discharge patterns of pairs of motor units was also examined, and it was found that significant coupling occurred at the stimulus frequency, superimposed on a 'background' coupling from unidentified sources. The phase relationship between pairs of motor units was not affected by the periodic stimulus. However, it was observed that if two motor units were firing independently of one another in the absence of capsule probing, maintained capsular indentation produced a striking synchronization between the discharges of the two motor units. These experiments show strong joint-mediated reflex effects on motor unit firing indicating that joint receptors may have an important role to play in motor control. PMID- 2271154 TI - Intracellular free magnesium and its regulation, studied in isolated ferret ventricular muscle with ion-selective microelectrodes. AB - Intracellular free magnesium ([Mg2+]i) was measured in isolated ferret papillary muscles using ion-selective microelectrodes filled with the new magnesium sensor ETH 5214. This new sensor, unlike its predecessor ETH 1117, does not react to marked changes in K+, Na+ or pH. Reducing Ca2+ from 20 microM to around 10 nM also did not affect the response so these electrodes are ideally suited to study intracellular Mg2+ and its regulation. The mean value for the [Mg2+]i from thirty two experiments (forty-two impalements) was 0.85 mM, confirming previous estimates from this laboratory. Intracellular Mg2+ is not passively distributed and the possibility that Mg2+ is transported out of the cell by a Na(+)-Mg2+ exchanger was investigated. An increase in [Mg2+]o caused an increase in [Mg2+]i, as did stepwise reduction in the [Na+]o. However, this increase in [Mg2+]i on Na+ reduction also occurred in Mg2(+)-free solution suggesting that the increase in [Mg2+]i was due to the increase in intracellular Ca2+ on Na+ reduction. Moreover, increasing [Na+]i by strophanthidin did not change the [Mg2+]i and on increasing [Mg2+]o there was no reduction in the [Na+]i. Blocking ATP production lead to small increases in the [Mg2+]i. These results are not consistent with a Na(+) Mg2+ exchanger as being the main outward transport mechanism for Mg2+ in this tissue. PMID- 2271155 TI - The intracellular concentration of free magnesium in extensor digitorum longus muscles of the rat. AB - Magnesium-sensitive microelectrodes were used to measure the intracellular concentration of free Mg2+, [Mg2+]f, in rat extensor digitorum longus muscles in vitro at 30 degrees C. The intracellular activities of Na+ and K+ were also determined so that allowance could be made for the interference from these ions with the Mg2+ electrode response. The mean value for [Mg2+]f based on twenty-six measurements in twelve muscles was 0.47 mM. PMID- 2271156 TI - Nutrient and pharmacological stimulation of insulin-secreting cells: marked differences in the onset of electrical activity. AB - Whole-cell current clamp experiments with the patch-clamp technique have been used to investigate the electrical activity of insulin-secreting (RINm5F) cells. When challenged with either glucose (10 mM), glyceraldehyde (10 mM), L-alanine (5 mM) or tolbutamide (100 microM) the cells depolarized and this led to the generation of spike potentials. Marked differences in the lag times between stimulation and the onset of electrical activity were observed. Both tolbutamide and L-alanine evoked spike potentials within on average 7 s of stimulation, whilst the effects of glucose and glyceraldehyde were only observed over a much longer delay. These variations may be explained by differences in the routes through which closure of ATP-sensitive K+ channels is brought about. PMID- 2271157 TI - The role of platelets in the reflex tachypnoeic response to miliary pulmonary embolism in anaesthetized rabbits. AB - Experiments were performed upon twenty-eight male Californian rabbits anaesthetized with sodium pentobarbitone and breathing room air. Successive injections of glass bead emboli (diameter 125 microns) caused an increase in respiratory rate, and decreases in tidal volume (tachypnoeic response) and platelet count. The tachypnoeic response was not observed in rabbits that had been rendered thrombocytopaenic by platelet antiserum. Induction of thrombocytopaenia by antiserum was accompanied by tachypnoea which was not significantly different (P greater than 0.05) from the response to emboli. The tachypnoeic response to antiserum, like that to emboli, was prevented by bilateral cervical vagotomy. Pre-treatment with aspirin (5 mg/kg), which inhibits the platelet-release reaction, also prevented the tachypnoeic response to both emboli and antiserum, although it did not prevent the fall in platelet count which following injection of antiserum. These data support the hypothesis that the post-embolic reflex tachypnoea is platelet dependent and may be secondary to the platelet-release reaction. PMID- 2271158 TI - Reflex co-ordination of corporal and antral contractions in the conscious dog. AB - This study characterizes the role of extrinsic nerves in the co-ordination of corporal and antral contractions in the dog. Fasting motor activity was recorded in conscious dogs with stomachs previously divided into separate corporal and antral pouches. Both corpus and antrum showed synchronized phases of activity and quiescence recognizable as migrating motor complexes (MMCs, duration 81.2 +/- 9.6 min, n = 4). Moreover, individual contractions were temporally linked such that corpus contractions, occurring at 76 +/- 4 s intervals, were each followed by a burst of one to three antral contractions at a frequency of 4-5 min-1. The mean latency between the onset of individual contractions in the corpus and antrum was 10.9 +/- 2.6 s (n = 4). Denervation of the antral pouch in two additional dogs did not affect the MMC cycle (mean durations 106.6 and 82.1 min) and the onset of activity in the corpus and antrum was generally co-ordinated but less precise. However, individual antral contractions were no longer linked to corporal contractions, occurring randomly throughout the corpus contraction cycle. This was associated with a lower contraction frequency in the denervated antral pouches than in the corpus (0.3 +/- 0.1 min-1 compared to 0.6 +/- 0.08 min-1). It is proposed that a vagal reflex, excited by corporal tension receptors, provides phasic excitation facilitating the generation of antral contractions. Such a reflex is likely to reinforce the myogenic mechanisms which occur in the intact stomach and thus plays a role in co-ordinating gastric peristalsis. PMID- 2271159 TI - Adaptation of the mechanisms controlling gastric motility following chronic vagotomy in the ferret. AB - Changes in gastric motility were studied in the urethane-anaesthetized ferret following acute or chronic (3 weeks) vagotomy. The stomach was divided into the corpus and antrum and the effects of vagotomy on tone, frequency and contraction amplitude were investigated separately in the two gastric regions. In the corpus tone is kept at low levels by vagal activation of nonadrenergic, non-cholinergic (NANC) inhibitory neurones and also tonic sympathetic inhibition of intramural cholinergic activity. Frequency of contractions is also low due to tonic inhibition of cholinergic neurones by the vagus but not the sympathetic nervous system. There appears to be little vagal involvement in contraction amplitude but there is sympathetic inhibition of this parameter again via inhibition of cholinergic neurones. In the antrum there is no vagally driven inhibition of tone but a sympathetic inhibition of cholinergic neurones tends to reduce tone in the intact animal. Frequency of contractions does not appear to be extrinsically modulated. The vagus is tonically excitatory with regard to contraction amplitude in the antrum whereas the sympathetic nervous system is inhibitory, again via inhibition of cholinergic neurones. After chronic vagotomy some adaptation appears to take place within the surviving control systems in both the corpus and the antrum. Changes in cholinergic function have been suggested previously and are corroborated in this study. In addition novel alterations in intrinsic NANC systems and the remaining sympathetic innervation have been demonstrated in both regions of the stomach which tended to reduce the effects of vagotomy and return values for the parameters measured toward those observed in intact animals. The contribution of the cholinergic, adrenergic and NANC neurotransmitter systems to the post-vagotomy motility patterns differed in the corpus and antrum. PMID- 2271160 TI - Assessment of bone turnover in the dry period of dairy cows by measurement of plasma bone GLA protein, total plasma alkaline phosphatase activity and urinary hydroxyproline. AB - Plasma osteocalcin, or plasma bone GLA protein (BGP), total plasma alkaline phosphatase activity and urinary hydroxyproline excretion of twenty-four pregnant dairy cows (thirteen in their first or second pregnancy, i.e. low parity, and eleven in their third or more pregnancies, i.e. high parity) were measured from 7 weeks before parturition until 1 week after parturition. Seven weeks before parturition the cows' ration was changed to one containing either 0.22% magnesium (low magnesium, LMg) or 0.82% magnesium (high magnesium, HMg) in the dry matter, and the potassium content of both rations was increased to approximately 4.1% in the dry matter to reduce the absorption of magnesium. Plasma BGP levels decreased significantly (P less than 0.01) as parturition approached while total plasma alkaline phosphatase activity and urinary hydroxyproline excretion did not. Magnesium supply and parity had no significant effect on this decrease. The overall plasma concentration of BGP, total plasma alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio in the prepartum period were affected by parity (P less than 0.05) with higher values in the lower parity cows. A significant positive correlation (r = 0.58, P less than 0.01) was found in all cows between plasma BGP level at parturition and the percentage of the bone surface covered with osteoblasts; however, plasma BGP was not correlated either with other histomorphometric variables or with total alkaline phosphatase activity during this time. PMID- 2271161 TI - A sodium-activated potassium current in intact ventricular myocytes isolated from the guinea-pig heart. AB - A current generated by the Na-activated K channel has been identified in whole cell currents recorded from isolated guinea-pig ventricular myocytes. A partial activation of this current can be achieved near to the physiological range of intracellular sodium concentration [( Na+]i) when it contributes significantly to the global outward current. The decline of the Na-activated K current, the lengthening of the action potential duration and the recovery of [Na+]i occur with a similar time course during recovery from Na loading. PMID- 2271162 TI - Sympathetic stimulation causes increased output of lymphocytes from the popliteal node in anaesthetized sheep. AB - Stimulation of the lumbar sympathetic chain at a frequency of 4 Hz caused a threefold increase in the lymphocyte output in efferent lymph from the popliteal node in anaesthetized sheep. The increase was accounted for by a rise in both lymph flow and lymphocyte count. Intra-arterial infusion of phentolamine (10 micrograms kg-1 min-1) abolished the nerve-mediated increases in flow and cell count. PMID- 2271163 TI - High-energy phosphates and fatigue during repeated dynamic contractions of rat muscle. AB - Reductions in work output during repeated contractions of rat medial gastrocnemius muscles (37 degrees C) were compared with changes in muscle metabolite concentrations. Three different exercise protocols were used in which the total number of stimuli and the length excursion were the same. The muscles performed a series of either 10, 25 or 40 repeated contractions at velocities of 20, 50 and 80 mm/s for groups A, B and C, respectively. In group A work output decreased steadily to 66% of the output in the first contraction. In groups B and C work output decreased to less than 10% of the first contraction. Changes in phosphocreatine and lactate concentrations were similar for all groups. However, very low ATP concentrations (approximately 35% of the resting value) were observed in groups B and C, compared with approximately 65% in group A. Inosine 5'-monophosphate (IMP) production was 9.9 mumol/g dry wt in group A and approximately 18 mumol/g dry wt in groups B and C. The results suggest fatigue does not depend on changes in intracellular inorganic phosphate and pH but possibly on changes in nucleotide metabolism. PMID- 2271164 TI - Subcellular elemental composition in isolated cardiac myocytes from rabbit following chronic potassium depletion and acute repletion, studied by X-ray microanalysis. AB - X-ray microanalysis was used to estimate K, Na, Cl, Mg, P and S within the mitochondria and the myofibrillar regions of cardiac myocytes from rabbits, following dietary potassium depletion. K depletion caused no changes in mitochondrial K, but myofibrillar K was reduced. There were no changes in Na, Mg or Cl. Both areas showed increases in P but decreases in S. Acute K repletion resulted in a significant overshoot of K in both areas, coupled with a profound decrease in Cl. P was reduced in the mitochondria alone. These results may be partly explained by adaptive changes in Na+ pump activity. PMID- 2271165 TI - Role of vagal afferent C fibres in the bradycardiac response to an increase in arterial blood pressure in ferrets. AB - The effects on baroreceptor reflexes of bilateral application of the C fibre neurotoxin, capsaicin, to the cervical vagi have been investigated in decerebrate ferrets. Baroreflex sensitivity was estimated from the relationship between cardiac interval and systolic blood pressure following I.V. infusion of phenylephrine. Control responses to phenylephrine were fitted by two linear slopes with an initial shallow slope, a, followed by a steeper slope, b. Capsaicin abolished slope b and the resulting relationship was best fitted by a single regression with a slope not significantly different from that of the control response a. This suggests that a significant proportion of the baroreflex response induced by phenylephrine is mediated by cardiopulmonary receptors attached to vagal afferent C fibres. PMID- 2271166 TI - A simple procedure for maximum yield of high-quality plasmid DNA. AB - We have established a simple procedure for the rapid isolation of high-quality plasmid DNA suitable for various molecular techniques and provided a step-by-step protocol. The DNA samples isolated by this procedure have been used successfully for double-stranded DNA sequencing, restriction enzyme mapping, subcloning, in vitro mutagenesis, generation of deletion clones and so on. The procedure is highly reproducible, and superior quality DNA can be obtained without the use of phenol, chloroform or other organic solvents. PMID- 2271167 TI - A rapid and simple method for screening large numbers of recombinant DNA clones. AB - A simple and rapid method has been described for the isolation of plasmid, phagemid and phage DNAs. Hundreds of recombinant clones can be screened in one day employing this method. It takes half an hour to prepare plasmid DNA from ten clones, and the DNA prepared from a single colony using this method is of sufficient quality and in sufficient amount to perform at least five restriction digestions. This method eliminates the need for RNase treatment and phenol chloroform extraction if the plasmids are needed only for the restriction digestion. If needed, RNAs can be removed after restriction digestion by adding RNase and incubating for two minutes at room temperature. After RNase treatment and phenol/chloroform extraction, the plasmid DNA serves as a good template for sequencing. The DNA can be stored at -20 degrees C for over eight weeks. PMID- 2271168 TI - A strategy for rapid identification and selection of site-directed low-frequency point mutations. PMID- 2271169 TI - Ethanol precipitation to concentrate DNA excised from agarose gel. PMID- 2271170 TI - Efficient subcloning of DNA fragments amplified by crude oligonucleotides. PMID- 2271171 TI - A method for the determination of sequence of high G+C% DNA by the sequential application of sequenase and Taq polymerase. PMID- 2271172 TI - An inexpensive 750-ml water bath. PMID- 2271173 TI - A quick protocol for plasmid DNA analysis. PMID- 2271174 TI - Photographic enhancement of faint autoradiogram data bands. PMID- 2271175 TI - An improved procedure for quantitating mitochondrial DNA in cultured mammalian cells. AB - A new improved method that reproducibly measures small perturbations of mitochondrial DNA in populations of cells has been developed. It is based on first obtaining a cell count and then analyzing three aliquots of cells: one for total DNA per cell by fluorometry, one for total protein per cell and one for the amount of mitochondrial DNA per microgram of total cell DNA. To quantitate mitochondrial DNA, 0, 1, 2, and 3 nanograms of mouse mtDNA purified from a plasmid are added as internal standard DNA to four 1.0-microgram samples of purified total cell DNA containing an unknown amount of mitochondrial DNA (a sample set). Three sample sets are electrophoresed in an agarose gel devoid of ethidium bromide. Following Southern transfer to nitrocellulose and hybridization to purified 32P-labeled mouse mitochondrial DNA, an autoradiogram is prepared for use as a template to locate the mitochondrial DNA bands. These bands are cut out of the nitrocellulose filters, and their 32P-content is determined using a liquid scintillation counter. For each sample set, the counts per minute is plotted against the amount of mitochondrial DNA added. The plot is linear and the negative average of the values for the three intercepts on the x-axis yields the amount of nanograms of mitochondrial DNA per microgram of total cell DNA. The method is highly reproducible with a standard deviation of approximately 9 percent. The advantages of using this method over others that have been reported are discussed. PMID- 2271176 TI - Direct cloning of the human genomic apolipoprotein E gene using magnetic separation of single-stranded DNA. AB - Solid-phase methods can be used for direct cloning of in vitro-amplified genomic DNA with high efficiency, without the need for restriction enzymes or ligase. Single-stranded DNA fragments are generated by magnetic separation and are simply mixed with single-stranded vector to form gap-duplex molecules that can be readily transformed. This strategy, in combination with direct solid-phase DNA sequencing, was used to analyze individual alleles in the human apolipoprotein E locus. PMID- 2271177 TI - HydroLink gel electrophoresis: rapid electroblotting of dsDNA. AB - Blotting and probing of DNA, RNA and proteins after electrophoresis is a powerful technique for the study of the structure and function of biomolecules. Key factors in successful blotting experiments are efficiency of transfer, maintenance of the resolution obtained during gel electrophoresis, accuracy of the probes used and sensitivity of the detection method. We have recently developed a system for the high performance resolution of DNA with 10-fold greater capacity for sample loads than agarose or polyacrylamide. In the present study, we describe conditions for the rapid (less than one hour) and quantitative electrotransfer of DNA in the 100-23,000-base pair range, with subsequent conditions for probing of transfer membranes using radioactive or biotinylated probes. Our results suggest complete maintenance of the high-resolution characteristic of HydroLink gel electrophoresis and potentially increased sensitivity due to the high loading capacity in HydroLink gel electrophoresis. PMID- 2271179 TI - Epidermal growth factor and related proteins in development. A MCDB/ISU symposium. August 25-28, 1989. Proceedings. PMID- 2271178 TI - Immobilon-P transfer membrane: applications and utility in protein biochemical analysis. AB - Polyvinylidene fluoride membrane for protein-blotting applications was introduced by Millipore Corporation in 1986. The membrane, designated variously as Immobilon PVDF, Immobilon-P Transfer Membrane and Immobilon-P, has been widely used in protein biochemical analysis. Applications developed using Millipore's polyvinylidene fluoride membrane span immunochemistry, cell biology and protein structural characterization. Additionally, protein analysis on Immobilon-P membrane has been interfaced to a range of separation methodologies including high-pressure liquid chromatography and both one- and two-dimensional electrophoresis. PMID- 2271180 TI - Expression of EGF and TGF-alpha genes in early mammalian development. PMID- 2271181 TI - EGF receptor activities in mammalian development. AB - The receptor for epidermal growth factor (EGF) and its analog transforming growth factor alpha (TGF alpha) is ubiquitous, implying quite general roles for EGF/TGF alpha in cell viability and tissue maintenance in adult tissues. There is also evidence that the EGF receptor is active in promoting wound healing and tissue regeneration in adult organs, such as skin, liver, and intestinal epithelium. It is likely that EGF receptors have more specific roles during the gestation period. For example, we have detected EGF receptors on the 3.5-day blastocyst (trophectoderm) surface and since TGF alpha-like mRNA sequences and peptides have been detected at this time (Rappolee et al., Science 241:1823, 1988), there is a strong implication for autocrine stimulation in pre- and peri-implantation stage embryos. Paracrine stimulation between the embryo and maternal tissues is also likely since both receptors and TGF alpha are present in decidual cells. Therefore EGF receptors may take part in growth regulation of the early embryo and in the process of implantation. Other examples where EGF receptors may play specific roles during embryonic development are discussed. PMID- 2271182 TI - Notch and the molecular genetics of neuroblast segregation in Drosophila. PMID- 2271183 TI - Molecular and genetic intimations of the function of Delta, and EGF-like gene required for ectodermal differentiation in Drosophila. PMID- 2271184 TI - Transforming growth factor-alpha. AB - In summary, although TGF-alpha was initially found in tumors, a number of later studies, some of them from the author's laboratory, have shown that TGF-alpha should no longer be considered a tumor associated growth factor. Rather, TGF alpha is a normal physiological ligand for the EGF receptor. Table 2 lists some of the normal cellular sources of TGF-alpha. Our list is incomplete, but we know that TGF-alpha is made in keratinocytes and a number of epithelial cells, including gut and breast epithelial cells. It seems very likely that TGF-alpha is a major growth factor secreted by cells of epithelial origin. Zena Werb's and Russell Ross's groups have shown that activated macrophages make TGF-alpha. We have shown that brain makes TGF-alpha and Jeff Kudlow has found TGF-alpha made in the pituitary. Data from several sources, including David Lee, the author's laboratory, and Zena Werb's laboratory has shown that TGF-alpha is made during embryonic development. Therefore, it is now important to look at TGF-alpha in its normal physiological context. Finally, it should be stressed that, as was mentioned above, TGF-alpha is not necessarily a secreted growth factor 50 amino acids long. There is quite a bit of processing of the larger precursor that may or may not take place. This processing, which determines the ultimate size and location of the molecule, is also likely to influence its physiological action. PMID- 2271185 TI - TGF-alpha: expression and biological activities of the integral membrane precursor. PMID- 2271186 TI - Regulation of EGF receptor expression and function. AB - From the results of these studies of the activities of the various EGF receptor mutants we were able to disassociate the ability of EGF to increase intracellular calcium from its ability to induce genes and to cause morphological transformation and growth. These results lead us to the following concept. The kinase domain has a C-terminal border at about residue 957. The remainder of the C-terminus is regulatory. The 164 amino acids from residue 1022 to 1186 constitute an inhibitory region for the kinase. It contributes to ligand-induced internalization because this is reduced in a mutant receptor truncated to residue 1052. Proximally within the C-terminus kinase inhibitory domain is a domain that is required for endocytosis and for raising intracellular calcium that we call the calcium internalization (CAIN) domain. In summary, we have found that the kinase activity of the EGF receptor is required for its function even when all of the self-phosphorylation sites have been removed. The EGF receptor has several distinct cytoplasmic domains that are important for its activity to regulate gene expression, DNA synthesis, and the intracellular calcium level. Biological signaling occurs from the cell surface via essential protein tyrosine kinase activity with ligand-induced internalization serving to abbrogate the biological signal. PMID- 2271187 TI - An evolutionarily conserved TGF-alpha/insulin-degrading enzyme. PMID- 2271188 TI - EGF receptors in the development of epitheliomesenchymal organs. PMID- 2271189 TI - A sea urchin gene containing multiple EGF repeats is similar to vertebrate EGF containing genes. PMID- 2271190 TI - Genetic and molecular analysis of EGF-related genes in Caenorhabditis elegans. PMID- 2271191 TI - Monoamine oxidase inhibitors: are we condemned to relive history, or is history no longer relevant? PMID- 2271192 TI - Gastric residual volume in infants and children following a 3-hour fast. AB - The effect of a 3-hour versus a 10-hour preoperative fasting interval on the gastric residual volume and gastric pH of pediatric patients was evaluated. Forty four healthy infants, 1 month to 5 years of age, were randomly assigned to one of two groups. The 3-hour nil per os (NPO) group consisted of 19 infants kept NPO for 3 hours following ingestion of up to 4 ounces of 5% dextrose in water (D5W). The control group consisted of 25 infants who remained NPO an average of 10 hours prior to surgery. Gastric residual volume was calculated using the dye-dilution technique. After the dye marker was injected into the stomach, complete aspiration of the stomach (including the volume of dye marker plus residual gastric contents) was attempted as another method to measure gastric residual volume. There were no significant differences in gastric residual volume between the 3-hour and the 10-hour NPO groups using either the dye-dilution or aspiration methods. However, there were significant differences between the two measuring techniques. Gastric residual volume was significantly greater in volume when measured by the dye-dilution technique than it was when measured by the aspiration technique in both the 10-hour (p less than 0.009) and the 3-hour (p less than 0.0009) NPO groups. Complete aspiration of a known volume of fluid injected through the orogastric tube was not possible in 23 of the 44 (52.4%) infants. Mean gastric pH was less than 2.0 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271193 TI - Anesthetic considerations in patients with chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is a rare, genetically transmitted disorder characterized by recurrent, life-threatening infections with catalase-positive micro-organisms and excessive inflammatory reactions that lead to granuloma formation. Long-term prophylactic antimicrobial agents and aggressive surgical management are the mainstays of therapy. The authors provided anesthetics for 17 patients with CGD undergoing 55 surgical procedures. These patients presented to surgery with multiple organ system involvement and were at significant risk for complications in the perioperative period. Granulomatous lesions of the gastrointestinal (GI) tract may predispose such patients to regurgitation and aspiration. PMID- 2271194 TI - Intravenous droperidol decreases nausea and vomiting after alfentanil anesthesia without increasing recovery time. AB - The frequency rate of nausea and vomiting after an alfentanil-based anesthetic is high, with reported frequencies of 38% to 68%. This study was undertaken to evaluate the efficacy of low-dose and moderate-dose droperidol in decreasing the frequency of postoperative nausea and vomiting and to evaluate whether droperidol has any effect on slowing recovery after a standard alfentanil-based anesthetic. Sixty normal adults who were scheduled to undergo short surgical procedures requiring general anesthesia were assigned randomly in a double-blind manner to one of three groups of 20: (1) control--normal saline; (2) droperidol 10 micrograms/kg; or (3) droperidol 20 micrograms/kg. A standard alfentanil-based anesthetic was used, and the study drug was given immediately after induction of anesthesia. In the post-anesthesia recovery room, all patients were evaluated according to the Aldrete score, noting the time to achieve a score of 10. Presence or absence and severity of nausea and vomiting were noted. To assess psychomotor recovery, a Trieger dot test was performed by every patient preoperatively, at the time of an Aldrete score of 10, and upon discharge from the recovery room. There was no statistical difference between the groups in age, sex, type of procedure, weight, total dose of alfentanil, or duration of anesthetic. The frequency of nausea and vomiting was significantly less (p less than 0.05) for the 20 micrograms/kg group (5%) than for the 10 micrograms/kg group (25%) or the control group (40%). A dose-response relationship was evident for the antiemetic effect of droperidol. An analog scale for severity of nausea and vomiting also demonstrated a dose response effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271195 TI - Ketamine induction and monoamine oxidase inhibitors. AB - A 42-year-old woman taking tranylcypromine, a monoamine oxidase (MAO) inhibitor, was hypovolemic from a ruptured ectopic pregnancy and required an emergency laparotomy. Anesthetic induction with ketamine, an agent with sympathomimetic properties, was used because of her hypovolemia, despite theoretical concerns of precipitating an adrenergic crisis. The patient's hemodynamic course remained unchanged with induction and intubation, and with further fluid and blood administration, satisfactory hemodynamic conditions were obtained. This report is believed to be the first to describe the use of ketamine in a patient taking MAO inhibitors. PMID- 2271196 TI - Perioperative rate-related silent myocardial ischemia and postoperative death. AB - A case is presented that demonstrates heart rate (HR)--related silent myocardial ischemia occurring preoperatively, subsiding intraoperatively, then recurring and leading to a post-operative cardiac death in a patient undergoing peripheral vascular surgery. This case illustrates that patients may have an ischemic threshold for HR whereby recurrent depression of the ST segment may occur during increase of HR to rates as low as 80 to 85 beats per minute (bpm), even in the absence of acute blood pressure (BP) changes. Myocardial ischemia may be HR related; however, the authors are not aware of a case that demonstrates repeated episodes of rate-related ischemia occurring at HRs well below the 100 bpm traditional definition of tachycardia. The authors conclude that patients at risk for perioperative myocardial ischemia should be identified and the hemodynamic management of these patients should include control of HR. This implies control of the physiologic variables that influence HR, along with the use of beta adrenergic blockers. This case also demonstrates the value of Holter monitoring for ischemia, which, when done preoperatively, can detect patients at risk for unfavorable cardiac outcomes. Ischemia monitoring also may be useful during the intraoperative and postoperative periods, a time when ischemia is often silent and undetected. The early recognition of ischemia would allow for anti-ischemic interventions, which could decrease the morbidity and mortality of patients at risk for perioperative cardiac complications. PMID- 2271197 TI - Anesthesia in 'stone man': myositis ossificans progressiva. AB - Myositis ossificans progressiva is a rare disease leading to complete ossification of the muscular system. Very little information about this rare disease and its anesthetic implications has appeared in anesthetic literature. This disease is felt to have an autosomal dominant pattern of inheritance and is usually associated with anomalies of the hands and feet. Afflicted patients are frequently misdiagnosed in childhood as having a rheumatologic disorder. Later in life (as true bone is formed in striated muscle, ligaments, and fascia), the correct diagnosis becomes obvious. Although muscles of the heart, diaphragm, larynx, and sphincters are spared, those of the chest wall are not, and pulmonary function progressively deteriorates. Death frequently occurs as a result of a pulmonary infection. Specific anesthetic considerations include positioning to avoid injury, potential need for fiberoptic intubation or tracheostomy, decreased thoracic compliance with the need for increased ventilating pressures, and the ultimate in disuse atrophy contraindicating the use of succinylcholine. Myositis ossificans progressiva can present the anesthesiologist with interesting challenges. Anesthetic management will need to be individualized according to the severity of the disease. PMID- 2271198 TI - A series of truly failed spinal anesthetics. AB - This report describes five patients with failed continuous spinal anesthetics with lidocaine. Lidocaine concentrations of 420 to 880 micrograms/ml were assayed in the spinal fluid despite lack of anesthesia. There was free flow of cerebrospinal fluid (CSF) through the catheter in all patients before and after the injection of lidocaine. Inactive lidocaine was not responsible for the failures, since lidocaine from the same manufacturing batch produced anesthesia in other patients. Incorrect catheter placement could not explain the failures, since bupivacaine injected through the same intraspinal catheter produced anesthesia in four of the five patients. The authors, therefore, suggest that some patients have a physiologic resistance to lidocaine. PMID- 2271199 TI - Regional versus general anesthesia for the high-risk patient. PMID- 2271200 TI - History of anesthesia in Japan. PMID- 2271201 TI - Sopiens suscitans. PMID- 2271202 TI - Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane, and isoflurane. AB - STUDY OBJECTIVE: To compare the volatile anesthetic sevoflurane with halothane, enflurane, and isoflurane on the uptake and biotransformation in humans. DESIGN: Prospective pharmacokinetic study of sevoflurane administration in human subjects. SETTING: Inpatient surgery clinic at a university medical center. PATIENTS: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia. INTERVENTIONS: The patients were assigned randomly to one of four groups: halothane, enflurane, isoflurane, or sevoflurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enflurane, 1.85%; isoflurane, 1.27%; and sevoflurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes. MEASUREMENTS AND MAIN RESULTS: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevoflurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m2/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m2/MAC; degradation rate 15.7%), enflurane (1150 ml/m2/MAC; 1.3%), and isoflurane (439 ml/m2/MAC; 0.6%) were also conducted. Sevoflurane had a peak serum inorganic fluoride concentration of 19.3 mumol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively. CONCLUSIONS: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC (1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rate was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane. PMID- 2271203 TI - High-frequency ventilation in neonates. AB - STUDY OBJECTIVE: To provide a brief review of the current status of high frequency ventilation in neonatal respiratory care. DATA IDENTIFICATION: Publications appearing between 1980 and 1990 were identified by computer searches using the National Library of Medicine's data base, MEDLINE, and by searching bibliographies of identified articles. STUDY SELECTION: Studies related to physiologic background and clinical reports of neonatal application were selected individually. DATA EXTRACTION: Data concerning the physiologic basis, clinical effectiveness and complications, and latest results of a multicenter randomized trial were evaluated and used to develop a current concept. RESULTS OF DATA SYNTHESIS: In early clinical tests of high-frequency ventilation, it was considered beneficial that airway pressure lower than that used in conventional mechanical ventilation might reduce the frequency of pulmonary barotrauma. When high-frequency ventilation was applied to infants with respiratory distress syndrome, the development of chronic pulmonary complications also was expected to decrease. Although several reports supported this hypothesis, a recent controlled trial involving multiple clinical centers did not find significant improvement in the group treated with high-frequency ventilation. Rather, they recognized the frequent occurrence of complications associated with high-frequency ventilation and suggested the prior use of conventional ventilation. However, a possible defect of this study design requires further studies to elucidate the source of these conflicting results. CONCLUSIONS: As a mode of mechanical ventilation, high frequency ventilation is useful for maintaining ventilation in patients with air leak syndrome or bronchopulmonary fistula or during bronchoscopic examination. But in general, its role as an alternative to conventional ventilation still remains controversial. PMID- 2271204 TI - Blood coagulation and autologous blood transfusion in cardiac surgery. AB - STUDY OBJECTIVE: To review the basic pathophysiology of altered coagulation associated with cardiopulmonary bypass and autologous blood transfusion in cardiac surgery. DESIGN: Review of rational use of heparin, mechanisms and treatment of coagulation disorders, and autologous blood transfusion. SETTING: Cardiac surgery in community and academic hospitals. PATIENTS: Adult cardiac surgical patients. MAIN RESULTS: Heparin is most commonly used for anticoagulation during cardiopulmonary bypass. Although activated clotting time is widely used to assess heparin-induced anticoagulation, the minimum time to prevent clotting during cardiopulmonary bypass remains unclear. Activated clotting time is affected by many factors other than heparin, such as antithrombin III, blood temperature, platelet count, and age. The rational use of activated clotting time still must be defined. The frequency of abnormal bleeding after cardiopulmonary bypass is significant. Although inadequate surgical hemostasis is the most frequent cause of bleeding, altered coagulation often is present. A decreased number of functional platelets is one of the important causes of bleeding diathesis. Platelet dysfunction is induced by perioperative medication such as aspirin. Cardiopulmonary bypass decreases functional platelets by degranulation, fragmentation, and loss of fibrinogen receptors. Medications such as prostacyclin and iloprost may be useful to protect these platelets. Desmopressin increases factor VIII:C and von Willebrand's factor, leading to a decrease in bleeding time. Desmopressin may be useful to decrease blood loss in repeat cardiac operations, complex cardiac surgery, and abnormal postoperative bleeding. Patients undergoing coronary artery bypass grafting immediately after streptokinase infusion also are at risk for abnormal bleeding. Transfusion of fresh-frozen plasma and cryoprecipitate may be necessary. Autologous blood transfusion is cost-effective and the safest way to avoid or decrease homologous blood transfusion. Predonation, intraoperative salvage, and postoperative salvage are encouraged. Erythropoietin may be useful in increasing the amount of predonation red cells. CONCLUSIONS: Coagulation disorders in cardiac surgery are caused by many factors, such as heparin, platelet dysfunction, and fibrinolysis. Rational use of blood component therapy and medications such as heparin, protamine, and desmopressin are mandatory. Autologous blood transfusion is very useful in decreasing or obviating the use of homologous blood transfusion. PMID- 2271205 TI - Effects of prostaglandin E1 on the cardiovascular response to tracheal intubation. AB - STUDY OBJECTIVE: To evaluate the efficacy of prostaglandin E1 in attenuating the hypertensive response to laryngoscopy and intubation. DESIGN: Controlled, comparative, and randomized study. SETTING: Induction of anesthesia for elective surgery at a university hospital. PATIENTS: Thirty normotensive patients (ASA physical status I) undergoing elective surgery divided into three groups. Each group consisted of ten patients. INTERVENTIONS: Anesthesia was induced with thiopental sodium 5 mg/kg intravenously, and tracheal intubation was facilitated with vecuronium 0.2 mg/kg. Either 0.3 micrograms/kg of prostaglandin E1, 0.6 micrograms/kg of prostaglandin E1, or saline (control) was injected 15 seconds before starting direct laryngoscopy (within 30 seconds), which was attempted 2 minutes after administration of thiopental sodium and vecuronium. MEASUREMENTS AND MAIN RESULTS: Patients receiving saline showed a significant increase in mean arterial pressure and rate-pressure product associated with tracheal intubation. These increases following tracheal intubation were significantly less in prostaglandin E1-treated patients than in the control group (p less than 0.05). CONCLUSIONS: A single rapid intravenous administration of prostaglandin E1 is a practical pharmacologic and safe method to attenuate the hypertensive response to tracheal intubation. The use of 0.6 micrograms/kg of prostaglandin E1 as a supplement during induction is recommended for reducing the pressor response to intubation on the basis of rate-pressure product and mean arterial pressure following intubation as an index. PMID- 2271206 TI - Was there a retained spinal catheter? AB - The 28-gauge catheter supplied by Kendall Healthcare Products Company (Mansfield, MA) for continuous spinal anesthesia has two important characteristics. The ink used for the centimeter calibration marks and to identify the tip of the catheter "washes off" while it is inserted in the patient. In addition, the catheter has a tendency to stretch while it is in the patient or being removed. These two characteristics produced a situation in which it was impossible to determine whether a catheter fragment had been left in a patient. This predicament had a serious impact on the postoperative management of the patient. A computerized tomographic scan and spine films were negative, while other evidence suggested that a fragment was left behind. When the patient developed a postdural puncture headache, the authors felt that an epidural blood patch was contraindicated. The patient's headache did resolve with 48 hours of conservative therapy. PMID- 2271207 TI - Effects of alfentanil or lidocaine on the hemodynamic responses to laryngoscopy and tracheal intubation. PMID- 2271208 TI - Difficult intubation cart. PMID- 2271209 TI - Chest applications of magnetic resonance imaging in children. AB - Mediastinal anatomy is well depicted by MRI. This article discusses the role of thoracic MRI in evaluating mediastinal, parenchymal, and pleural abnormalities in children. It is particularly useful in the evaluation of vascular anomalies and assessment of extension of neuroblastoma and can obviate other, more invasive, studies. PMID- 2271210 TI - Magnetic resonance imaging of abdominal and pelvic masses in children. AB - Magnetic resonance imaging is an excellent cross-sectional imaging study for the evaluation of pediatric pathology. This article outlines its role in the evaluation of abdominal masses in children, including lesions arising in the adrenal glands, kidneys, liver, and pelvic organs. PMID- 2271211 TI - Magnetic resonance imaging of pediatric atraumatic musculoskeletal lesions. AB - MRI has become a useful study for evaluating the musculoskeletal system. This article discusses the technique of pediatric musculoskeletal MRI and its practical applications. MRI appearances of various pathologic entities, including infection, neoplasms, marrow disorders, and joint diseases, are also reviewed. PMID- 2271212 TI - Magnetic resonance imaging of pediatric musculoskeletal trauma. AB - MRI is an important tool for evaluating acute and chronic injuries to the musculoskeletal system. It is effective in demonstrating abnormalities in the knee and hips and in detecting bone and ligamentous trauma that is not evident radiographically. PMID- 2271213 TI - [Incidence and forms of clinical presentation of the various morphologic types of myocardial laceration in the acute phase of infarct. A 4 years' caseload at a coronary unit. A clinico-anatomic study of 193 successive cases]. AB - AIMS: To determine the incidence of different morphological type of myocardial laceration (wall rupture) in patients who died of acute myocardial infarction, as well as to study the several clinical forms of presentation of different types of myocardial laceration. CONCEPT OF THE STUDY: To apply a protocol of prospective study, that includes 64 clinical and 34 anatomical parameters, using very discriminative technics in the anatomical study, already presented in previous papers. PLACE OF THE STUDY: The study took place in a CCU and pathological department of a University Hospital. POPULATION: Of 1308 patients successively admitted in a CCU with acute myocardial infarction between 1983-1986, 252 have died. It was possible to perform a necropsy study in 193. The only criterion for inclusion was the family agreement. METHODS: The study was a prospective one, being excluded only the patients in whom the anatomical study didn't confirm recent myocardial infarction. The clinical data were observed during the stay in the CCU, using a protocol developed for this study. In the anatomical study a protocol developed by the authors was applied, using very discriminative anatomical quantification technics of the infarct size as well as of the coronary obstruction degree by atherosclerotic plaques. In the study of the myocardial laceration a fourteen septal perpendicular cuts technic was applied, with a laceration development macroscopic study, and microscopic study of the more interesting cuts. All data were stored and treated in a computer program developed for this study. RESULTS: From the 193 cases that have been studied, 49 presented a complete free wall rupture (25%) and in two others there were an interventricular septal rupture and free wall rupture. The amount of free wall rupture was then 51 cases (26%), with a corrected incidence for the population with AMI of 5.1%. In 7 cases we found an interventricular septal rupture (in two cases associated with complete free wall rupture and in other two cases with an incomplete left ventricular rupture), what represents an incidence in necropsy of 3.6%. Since that in this period five patients with septal rupture have been operated and in three others the hemodynamic diagnosis was made, dying this patients without being performed necropsic study, the amount of septal ruptures was of 15 cases, what represents a corrected incidence of 1.1% in the population with AMI. The clinical forms of presentation of free wall rupture were the following: syncope followed by death (60%), shock (21%), transitory syncope (4%), psycho-motor troubling (4%). Pain persistence or recurrence associated with other clinical symptoms occurred in 63% of the patients. Hypotension, not always evoluting to shock, occurred in 33%, and pericarditis in 21% of the cases. When the different anatomical types of free wall rupture were considered (type I direct rupture; type II-multicanalicular rupture; type III-rupture covered by an interventricular thrombus), we observed that in type I there was prevalence of syncope (71% and only 50% showed pain persistence or recurrence, when in type II syncope occurred in 67% and shock in 22%, with pain in 56%, and in type III the occurrence of syncope and shock were similar (44% vs 38%), with pain in 81% of the cases. Hypotension was verified in 56% in type III, 21% in type I and 22% in type II. Pericarditis never occurred in type I, happened in 33% in type II and 25% in type III. The terminal accident took an average 44 minutes long in type I, 3.8 hours in type II and 9.2 hours in type III. The delay in admission was nine hours in type I, 19 in type II and 30 in type III, and the time between the onset of symptoms and death was 2.9, 2.7 and 5.4 days respectively in types I, II and III. In what concerns the interventricular septal rupture shock occurred in all cases but one, in which association with free wall rupture determined cardiac tamponade with syncope.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271214 TI - [Pre- and post-operative echocardiographic evaluation of the anomalous origin of the left coronary artery from the pulmonary trunk]. AB - OBJECTIVE: Pre and postoperative Doppler echocardiographic assessment of the anomalous origin of the left coronary artery from the pulmonary trunk (OLCAPT). MATERIAL AND METHODS: We analyzed Doppler echocardiographic diagnostic signs, the potential for recovery of left ventricular (LV) function and mitral regurgitation (MR) in 4 patients with OL-CAPT, treated by direct aortic implantation. The age at surgery ranged from 1 to 10 years and the follow-up from 3 months to 6 years. Doppler echocardiographic diagnostic study was performed at the first examination whereas LV function and MR were studied before (3 to 8 days) and serially after surgery. RESULTS: The OLCAPT was visualized in 3 patients and the retrograde flow from the anomalous left coronary in 1. An important right coronary artery dilation was present in 2 patients, being moderate in a third patient. Before surgery, the LV shortening fraction ranged from 17 to 23% and the ejection fraction from 23 to 36%. The qualitative analysis of segmental LV wall motion showed septal akinesis and hypokinesis of the remaining segments. Nine to 12 months after surgery, global and regional indexes of LV function improved, reaching the normal range except for the interventricular septum. In 2 patients with more than 2 years of follow-up, complete normalization of LV function was obtained, as well as with the electrocardiographic features of an old myocardial infarction in one case and a marked decrease in Q wave depth in the other. A moderate to severe MR was detected in all patients which improved markedly after surgery in 3. In the other case, a mitral replacement was necessary. CONCLUSION: Doppler echocardiography allowed: 1. the anatomic diagnosis in 3 of 4 patients with OLCAPT; 2. to follow global and regional LV function and MR improvement after direct aortic implantation of the anomalous left coronary artery. PMID- 2271215 TI - [Cardiovascular risk factors in the list of patients of a general practitioner]. AB - OBJECTIVE: Study the prevalence of cardiovascular risk factors in the list of patients of a general practitioner (GP). DESIGN: Study cardiovascular risk factors of all patients of a family doctor. SETTING: Health Center. PATIENTS: All the patients of a GP appointment (n = 1143). INTERVENTIONS: To study the clinic cards of all the patients of a GP appointment (n = 1143), in connection with the existence of cardiovascular risk factors: dyslipidemia, hypertension, smoking, obesity, diabetes and lack of physical exercise. To study these factors by age groups, sex and its association. RESULTS: From the 1143 patients, 62.8% showed at least one vascular risk factor; 14.9% two, 8.7% three, and 5% four or more. As a whole risks factors with more prevalence were obesity (26.5%), hypertension (24.5%), lack of exercise (24.1%), smoking (16.8%) dyslipidemia (12.7%) and diabetes (4.6%). The 1143 patients were 417 men and 726 women. Comparing sexes, obesity and lack of exercise were outstanding in women; smoking, hypertension, dyslipidemia and the association of risk factors were more frequent in men. All risk factors increased with age. CONCLUSIONS: From the present work we conclude that the majority of these patients appear to have at least one risk factor of cardiovascular disease and about a quarter association of risk factors. GP can and should take advantage of the privilege situation which occupies in terms of knowledge of its population to trace and if possible to control the present vascular risk factors. PMID- 2271216 TI - [Exercise 2D-Doppler echocardiography, for the evaluation of aortic valve prostheses]. AB - STUDY OBJECTIVE: Exercise evaluation of eccentric monocuspid aortic prosthetic valves. DESIGN: Prospective study, using 2D Doppler echocardiography to analyse resting and exercise aortic flow patterns. SETTING: Laboratory of Echocardiography at Santa Marta Hospital. PATIENTS: Sequential sample of 28 patients with aortic prosthesis (19 Bjork-Shiley and 9 Hall-Kaster), without evidence of either cardiac failure, coronary artery disease, prosthesis dysfunction or stress test contraindication. INTERVENTIONS: Transaortic basal and exercise flow record, using Doppler echocardiography to analyse: instantaneous peak velocity (pv) and gradient (pg), systolic time intervals, heart rate (hr) and stress test time (stt). The patients were divided in two groups A (prosthesis valve size 19 and 21) and B (greater than 21). RESULTS: Technical success: 84%. basal pv ranged from 1.6 to 4.5 m/s in group A and 1.7 to 3 m/s in B. Rest pg was 35 +/- 1% mmHg--Group A--and 20 +/- 8 mmHg in B (p less than 0.01), increasing with stress test respectively to 62 +/- 26 (p less than 0.01) and 36 +/- 12 mmHg (p less than 0.001). 73% of group A patients had exercise pg greater than 50 mmHg. The correlation between basal and exercise pg was significant (r = 0.91 p less than 0.001). At rest the systolic time intervals revealed a significant difference between the two groups (p less than 0.05), while only the ejection time was significant with stress test (p less than 0.01). Exercise hr and stt were greater in group B-p = NS. CONCLUSIONS: These exercise Doppler echocardiography data suggest that mechanical moncuspid aortic prosthesis 19, 21 and same 23, result in left ventricular outflow obstruction mainly during exercise; these facts should be taken into account when aortic prosthesis insertion is considered. Given the good correlation between resting and exercise peak gradient, Doppler stress test is not routinely recommended in clinical practice. PMID- 2271217 TI - [A case of perforation of the interventricular septum with free wall rupture, in the acute phase of myocardial infarct, successfully treated with surgery]. AB - The authors present a case of interventricular septal rupture with left ventricular free wall rupture post acute myocardial infarction operated on the third day after the onset of symptoms, by enfartectomy and application of a septal patch. Then, they compare this case with four cases referred in the literature, discussing the different and similar points between them. They emphasize the good results of this kind of surgery, but they also remark the need of an early diagnosis and surgery in these patients. PMID- 2271218 TI - [Temporary pacing in the prevention and treatment of tachyarrhythmia]. AB - In this article cardiac pacing is approached as a method to prevent and treat tachyarrythmias. The authors describe both the ways and places of stimulation as well as the indication to its use. The risks and complications associated to this method are also mentioned. In conclusion they refer to it as an available alternative to the other forms of antiarrythmic therapy, emphasising its efficacy and safety. PMID- 2271219 TI - [Clinical decision analysis. III--General aspects of the statistical content of the information given by diagnostic tests]. PMID- 2271220 TI - [Clinical decision analysis. IV. Real and apparent limitations of the binary matrix of clinical decision-making]. PMID- 2271221 TI - Uncommon pathways of metabolism among lactic acid bacteria. AB - A small number of lactic acid bacteria possess the ability to derive energy from organic molecules not utilized by the vast majority of representatives of this large group of microorganisms. Thus, strains of Lactobacillus casei and enterococci readily grow at the expense of substrates such as gluconate, malate and pentitols. Transport of gluconate and pentitols is catalysed by phosphotransferase systems unique to these bacteria. Similarly, the initial steps in pentitol dissimilation are mediated by enzymes found only in Lb. casei and Streptococcus avium. PMID- 2271222 TI - Genetics of the proteolytic system of lactic acid bacteria. AB - The proteolytic system of lactic acid bacteria is of eminent importance for the rapid growth of these organisms in protein-rich media. The combined action of proteinases and peptidases provides the cell with small peptides and essential amino acids. The amino acids and peptides thus liberated have to be translocated across the cytoplasmic membrane. To that purpose, the cell contains specific transport proteins. The internalized peptides are further degraded to amino acids by intracellular peptidases. The world-wide economic importance of the lactic acid bacteria and their proteolytic system has led to an intensive research effort in this area and a considerable amount of biochemical data has been collected during the last two decades. Since the development of systems to genetically manipulate lactic acid bacteria, data on the genetics of enzymes and processes involved in proteolysis are rapidly being generated. In this review an overview of the latest genetic data on the proteolytic system of lactic acid bacteria will be presented. As most of the work in this field has been done with lactococci, the emphasis will, inevitably, be on this group of organisms. Where possible, links will be made with other species of lactic acid bacteria. PMID- 2271223 TI - Health and nutritional benefits from lactic acid bacteria. AB - There are several potential health or nutritional benefits possible from some species of lactic acid bacteria. Among these are: improved nutritional value of food, control of intestinal infections, improved digestion of lactose, control of some types of cancer, and control of serum cholesterol levels. Some potential benefits may result from growth and action of the bacteria during the manufacture of cultured foods. Some may result from growth and action of certain species of the lactic acid bacteria in the intestinal tract following ingestion of foods containing them. In selecting a culture to produce a specific benefit it is necessary to consider not only the wide variation among species of the lactic acid bacteria but also that among strains within a given species. With the possible exception of improving lactose utilization by persons who are lactose maldigestors, no specific health or nutritional claims can yet be made for the lactic acid bacteria. PMID- 2271224 TI - Applications for biotechnology: present and future improvements in lactic acid bacteria. AB - The lactic acid bacteria are involved in the manufacture of fermented foods from raw agricultural materials such as milk, meat, vegetables, and cereals. These fermented foods are a significant part of the food processing industry and are often prepared using selected strains that have the ability to produce desired products or changes efficiently. The application of genetic engineering technology to improve existing strains or develop novel strains for these fermentations is an active research area world-wide. As knowledge about the genetics and physiology of lactic acid bacteria accumulates, it becomes possible to genetically construct strains with characteristics shaped for specific purposes. Examples of present and future applications of biotechnology to lactic acid bacteria to improve product quality are described. Studies of the basic biology of these bacteria are being actively conducted and must be continued, in order for the food fermentation industry to reap the benefits of biotechnology. PMID- 2271225 TI - Molecular genetics of Streptococcus thermophilus. AB - The metabolism and genetics of Streptococcus thermophilus (presently Streptococcus salivarius ssp. thermophilus) have only been investigated recently despite its widespread use in milk fermentation processes. The development of recombinant DNA technology has allowed impressive progress to be made in the knowledge of thermophilic dairy streptococci. In particular, it has permitted a careful analysis of phenotypically altered variants which were derived from a mother strain by plasmid or chromosomal DNA reorganization. While natural phage defense mechanisms of S. thermophilus remain poorly documented, information on the bacteriophages responsible for fermentation failures has accumulated. The lysogenic state of two S. thermophilus strains has also been demonstrated for the first time. Gene transfer techniques for this species have been established and improved to the point that targeted manipulation of their chromosomal determinants is now feasible. Cloning and expression vectors have been constructed, and a few heterologous genes were successfully expressed in S. thermophilus. The first homologous genes, involved in carbohydrate utilization, have been cloned and sequenced, shedding some light on the molecular organization of key metabolic steps. PMID- 2271226 TI - Temperate bacteriophages and lysogeny in lactic acid bacteria. AB - Lysogeny is widespread in the lactic acid bacteria. The majority of lysogens can be induced by UV irradiation or treatment with mitomycin C, but indicator strains which allow lytic growth of the induced phage are often not easy to identify. A few temperate phages have been shown to transduce chromosomal and/or plasmid markers. Information about the molecular biology of the temperate phages from lactic acid bacteria is sparse and needs significant supplementation in order that these potentially valuable phages might be utilized more efficiently as tools for improving existing starter strains in dairy fermentations. PMID- 2271227 TI - An alternative to the LD50? PMID- 2271228 TI - Study on kidney function in female workers exposed to perchlorethylene. AB - 1. Biochemical markers of kidney damage were examined in 16 female workers chronically exposed to tetrachlorethylene (TCE) in five dry-cleaning shops. The results were compared with those obtained in 13 females non-occupationally exposed to organic solvents. 2. The intensity of exposure was monitored by personal environmental monitoring. The time-weighed average exposure to TCE amounted to 157 mg m-3 (range 9-799 mg m-3). A satisfactory agreement was found between the concentration of TCE in ambient air sampled with the charcoal tube method and with a passive dosimeter. 3. The urinary excretion of lysozyme was increased in the exposed group. No difference was found in the urinary excretion of albumin, beta 2-microglobulin, lactate dehydrogenase, total proteins or glucose. The prevalence of abnormal values of biochemical parameters in the exposed group did not differ from that observed in the control group. No correlation was found between the level of TCE exposure and biochemical parameters. 4. The present study suggests that chronic exposure to TCE does not lead to renal damage. PMID- 2271229 TI - Pre-embarkment prognostication for acute paraquat poisoning. AB - 1. In order to assess which laboratory parameters could be related to the prognosis of patients with acute paraquat poisoning, we reviewed the medical records of 160 patients who had ingested paraquat in an attempt at suicide. 2. Serum creatinine and potassium concentrations, arterial blood bicarbonate and base excess levels, arterial blood pH, volume of paraquat ingested and the strength of the urinary paraquat qualitative test (sodium dithionate colour reaction) on admission in the surviving patients were significantly different from those of the patients who died within 48 h of ingestion. 3. The relationship of the quantity Eq1 defined as: Eq1 = ([K+] x [HCO3-])/([Cre] x 0.088) (mEq l-1) against the interval of time after ingestion to admission (T) had a significant correlation with prognosis (P less than 0.01). Patients with Eq1 greater than (1500 - 399 X LogT) had a 90% survival rate, Eq1: (930 - 399 X LogT) less than Eq1 less than or equal to (1500 - 399 X LogT) 38% and Eq1 less than or equal to (930 - 399 X LogT) 3%, P less than 0.01. PMID- 2271230 TI - Cytogeneticity of quinalphos and methyl parathion in human peripheral lymphocytes. AB - 1. Four different concentrations of quinalphos and methyl parathion were tested on human peripheral lymphocytes over different time periods, for the analysis of chromosomal aberrations and sister chromatid exchanges (SCEs). 2. A significant increase in chromosomal aberrations was observed when cells were treated with quinalphos for 48 and 72 h and a significant increase in SCEs was observed at all the concentrations and over all the time periods. 3. Methyl-parathion did not induce chromosomal aberrations but it did induce SCEs significantly over all time periods. PMID- 2271231 TI - Depletion of plasma glycine and effect of glycine by mouth on salicylate metabolism during aspirin overdose. AB - 1. The metabolism of aspirin was investigated in 45 patients who had taken self administered overdose of aspirin and were treated with fluids only, glycine, N glycylglycine by mouth, or by sodium bicarbonate i.v. 2. The major metabolite recovered in the urine of patients treated with oral fluids, glycine or N glycylglycine was salicyluric acid, which accounted for means of 51%, 47% and 38% of the total, respectively; salicylic acid comprised 19%, 29% and 29%. In contrast, salicylic acid (42%) was the major urinary metabolite recovered from patients treated with sodium bicarbonate. 3. Plasma glycine concentrations in healthy volunteers who had taken no aspirin remained constant through the day and were not affected by a therapeutic dose (500 mg) of aspirin. Plasma glycine was consistently lower in patients with aspirin overdose than in these healthy volunteers, suggesting depletion of available glycine. 4. Orally administered glycine and N-glycylglycine increased plasma glycine. While the fraction of total salicylate recovered as salicyluric acid was not altered, the maximum rate of excretion of salicyluric acid was higher in patients who received glycine than in the control group; there was no significant difference in the maximum rate of excretion of salicyluric acid between the group that received glycine and the group that received N-glycylglycine. 5. The data suggest that exogenous glycine increases the rate of formation of salicyluric acid in salicylate overdose. PMID- 2271232 TI - Phthalate esters, cystic kidney disease in animals and possible effects on human health: a review. AB - 1. Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2. DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3. Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4. More studies are needed on the mechanism of renal cystogenesis. PMID- 2271233 TI - A study of the interaction between lornoxicam and warfarin in healthy volunteers. PMID- 2271234 TI - Acute poisoning with methidathion: a case. AB - An acute poisoning in a 50-year-old man who ingested approximately 6.2 g of the phosphorus ester methidathion is described. The patient was treated with three haemoperfusions 23, 44 and 115 h after ingestion, with continuous gastric lavage, atropine and pralidoxime administration and with prolonged mechanical ventilation. Haemoperfusion was an ineffective epuration technique since it removed only 0.22% of the ingested methidathion. The clinical course wavered because of a probable redistribution of phosphorus ester from fat to blood. A plasma level higher than 100 micrograms l-1 was associated with the most serious phases. Methidathion was present in the plasma until the sixth day, in the urine until the seventh and in the gastric juice until the eighth. Its absence in the fat biopsy made on the tenth day was an aid to therapy. The phosphorus ester did not inhibit lymphocyte neuropathy target esterase (NTE), neither did it induce development of delayed polyneuropathy. PMID- 2271235 TI - [Surgical correction of mitral valve stenosis and its recurrence]. AB - The article analyses the results of surgical treatment of 1,394 patients with mitral stenosis who were operated on in the period between January 1, 1986 and April 1, 1989. Hospital mortality was 2.0%. Distinct indications for transventricular commissurotomy and mitral valve prosthetics were determined. The choice of the method for mitral stenosis correction was based on the character of the morphological changes in the cusps and subcuspal structures, which were determined during echocardiographic examination. With proper indications transventricular commissurotomy presents a small risk. Hospital mortality was 0.8% in mitral stenosis (among 1,039 patients who underwent operation 8 died) and 2.5% in recurrent stenosis (among 197 patients 5 died). Lethal outcomes were not encountered in stage 11, the mortality rate was 0.6% in stage III and 2.2% in stage IV. Mitral valve prosthetics was performed in 158 patients with 15 (9.5%) lethal outcomes. Hospital mortality was 4.5% in stage III and 10.3% in stage IV of the disease. In the group of patients with mitral stenosis hospital mortality was 7.5% (93 patients underwent operation). Hospital mortality after operations for recurrent mitral stenosis (65) was 12.3%. The initial severity of the patients' condition is still the main factor which influences unfavorably of the immediate results of mitral valve prosthetics. PMID- 2271236 TI - [Reconstructive vascular surgery in stenosis and kinking of the internal carotid artery]. AB - Combination of stenosis and kinking of the internal carotid artery was revealed in 7.9% of 126 patients who underwent operation for stenosis of the bifurcation of the carotid artery. Among 9 patients with kinking of the internal carotid artery (ICA) 5 had a C-shaped kink, 2 - an S-shaped kink, and 2 patients looping of the artery. The combination led to a great measure to diminished volumetric cerebral blood flow (30-35 ml/min/g). The operations were performed under conduction anesthesia. Average time of ICA compression - 13 min. 26 sec. Retrograde pressure ranged from 42 to 88 mm Hg. In 2 cases the ICA was implanted into a new opening in the common carotid artery after eversion endarterectomy. The defect in the bifurcation was sutured. In 5 cases (4 with a C-shaped kink and 1 with an S-shaped kink) the artery was replanted into the former opening after eversion endarterectomy and resection of the kinked segment of the ICA. In 2 patients with looping of the artery the loop was resected with end to end anastomosis into the ICA and typical endarterectomy from the bifurcation of the carotid artery. There were no fatal outcomes. The results of operative treatment were good. PMID- 2271237 TI - [Surgical treatment of post-anastomosis aneurysm developed after reconstructive operations on the thoracic aorta]. AB - Twenty-three patients were examined and operated on for aneurysms of anastomoses which formed after reconstructive operations on the thoracic aorta for its coarctation (15), kinking of the arch of the aorta (4), traumatic aneurysms (2), nonspecific aortoarteritis (1) and dissecting aneurysm (1). The involved segment had to be repaired with a prosthesis in all operations carried out for the second time. In 30% of patients the course was complicated (aortopulmonary fistulas, false aneurysm with dissection of the descending thoracic aorta). Mortality was 57% in a complicated course and 6.3% in uncomplicated cases. The results of the operation were good in 18 patients. PMID- 2271238 TI - [Treadmill test in objective evaluation of late results of radical correction of tetralogy of Fallot]. AB - The many-stage treadmill test was carried out according to a worked-out program in 41 patients before and in 55 patients after radical correction of Fallot's tetrad (40 healthy individuals were the controls). The pump function of the heart (oxygen debt dynamics), the anaerobic threshold (complex of gas analytical indices), and the efficacy of blood flow in lesser circulation (O2 consumption plateau) were appraised. The results proved to be best according to all criteria in patients with trans-annuloplasty of the conus arteriosus and pulmonary trunk with the use of a monocusp graft, and poorest in patients who were operated on through a transverse approach. This regularity was also encountered in 31 patients who were studied in follow-up periods of 3 years after the operation. PMID- 2271239 TI - [Comparison of the characteristics of myocardial function and metabolism in patients with tetralogy of Fallot]. AB - The authors studied the results of examination of the myocardium in patients with Fallot's tetralogy by means of two methods during radical correction of the congenital anomaly: invasive intraoperative myocardiography and appraisal of myocardial metabolism. High probability of the detection of dysfunction of the myocardium and disorders of of oxygen-dependent metabolic processes in it were revealed. A conclusion is drawn on the expediency of using invasive intraoperative myocardiography as a method of functional diagnosis in surgery of congenital heart diseases for appraising the condition of the myocardium. PMID- 2271240 TI - [Angiocardiographic diagnosis of solitary heart ventricle]. AB - The article deals with urgent problems of angiocardiographic diagnosis of a solitary ventricle of the heart. A program of roentgeno-surgical++ examination of patients with a solitary ventricle is suggested on the basis of conducted research. PMID- 2271241 TI - [Pulmonary hypertension in surgery of ventricular septal defects]. AB - The article discusses the appraisal of the degree of pulmonary hypertension and surgery of a ventricular septal defect with pulmonary hypertension in 108 patients whose ages ranged from 8 months to 31 years. The hemodynamic and morphological manifestations of pulmonary hypertension were found to increase with age. The hemodynamic manifestations of the anomaly may be similar in different types of changes of the vascular wall. A sharply hypertrophied middle muscular coat may be the cause of residual high pressure after closure of the defect, but with gradual reduction in contrast to the stable increase in sclerosis of the vascular lumen. This predetermines lung biopsy as an obligatory method for verifying the severity of pulmonary hypertension, which together with the hemodynamic data allows the indications for closure of the ventricular septal defect to be determined. PMID- 2271242 TI - [Correction of blood hyperviscosity in patients with chronic post-embolic pulmonary hypertension by the method of infusion of UV-irradiated autologous blood]. AB - Examination of 38 patients with chronic postembolic pulmonary hypertension revealed gross hemorheological disorders: increased viscosity of blood, extreme aggregation activity of blood cells, diminished property or erythrocytes to undergo deformity when circulating through the capillaries. Small amounts of UV irradiated autologous blood were infused repeatedly for the correction of these disorders. After a course of treatment the hemorheological indices were normalized in all the patients, which was attended by improvement of the general condition and positive hemodynamic shifts. PMID- 2271243 TI - [Use of cryopreserved autologous thrombocytes in cardiac surgery]. AB - Cryopreserved autologous thrombocytes were used for the prevention of thrombohemorrhagic complications after operations with extracorporeal circulation in 17 patients. An obvious hemostatic effect was produced. Studies carried out in cardiosurgical patients showed satisfactory maintenance of the main hemostatic characteristics of the blood platelets during cryopreservation. Plasma thrombocytapheresis in an apparatus allows simultaneous preparation of the autothromboconcentrate and large amounts of autoplasma used for filling the extracorporeal circulation apparatus, and compensation for the blood loss. PMID- 2271244 TI - [Comparative evaluation of Soviet-made mechanical prostheses in the mitral position]. AB - The authors appraised comparatively the 25 ball prosthesis (group 1), the rotational-disk prosthesis (group 2) and the prostheses (group 3) in 180 patients who underwent operation in the period between 1983 and 1988. The hospital lethality was 7.5% in group 1, 2.7% in group 2, and 4.8% in group 3. After dismissal from the clinic 98.2% of patients were studied in postoperative periods of 6 months to 5 years. Five-year survival after operation was 76.6 +/- 3.6%, 97.3 +/- 0.8%, and 87.7 +/- 1.2%, respectively. By the 5th postoperative year, no thromboembolic complications were encountered in 88.3 +/- 3.6% of patients in group 1, 97.3 +/- 0.8% of patients in group 2, and 91.5 +/- 2.4% of patients in group 3. The mean diastolic gradient was 7.05 +/- 0.75 mm Hg on the prosthesis, 3.98 +/- 0.44 mm Hg on the prosthesis, and 4.27 +/- 0.47 mm Hg on the prosthesis. At the time of the examination, 87.5% of group 1 patients, 88.2% of group 2 patients, and 87.1% of group 3 patients were related to I and II functional classes. PMID- 2271245 TI - [Sclerotherapy of telangiectasis]. PMID- 2271246 TI - [Experimental allogeneic transplantation of the trachea]. PMID- 2271247 TI - [Use of sanative fibrobronchoscopy with controlled high-frequency pulmonary ventilation after operations on the thoracic organs]. AB - The authors developed a method of sanative fibrobronchoscopy with the use of directed high-frequency stream ventilation with oxygen. A total of 108 procedures were conducted in 64 patients for removal of pulmonary complications after operations on the thoracic organs. The positive results of the method were confirmed by authentic improvement of the indices of external respiration function and increase of blood pO2 by 102% on the average. No improvement of similar indices was encountered in patients of the control group, while the blood pO2 reduced by 13.4% on the average. It is concluded that the method is very effective and safe, as compared to the traditional method of sanative fibrobronchoscopy in patients after interventions on the thoracic organs. PMID- 2271248 TI - [Endobronchial use of hemostatic drugs feracryl and amifer]. AB - The results of endoscopic administration of hemostatic agents feracryl and Amifer in 147 cases are analysed. In 123 patients 5-10 ml of 1% feracryl were administered after endobronchial bioptic manipulations. Bleeding after collection of bioptic material from the bronchial mucosa was arrested by this method in 69 cases. Moderate bleeding in 42 cases was arrested by pressing to the wound surface a tampon saturated with a feracryl solution. Endoscopic occlusion of a bleeding bronchus by means of feracryl and Amifer was conducted in 16 patients with various forms of lung tuberculosis complicated by hemoptysis and pulmonary hemorrhage. In 9 cases with massive pulmonary hemorrhage 3-4 ml of 20% Amifer solution was administered by endobronchial route into the bleeding area. In 7 cases up to 10 ml of feracryl was introducedby ++endobronchial route. Temporary endoscopic hemostasis in patients with various forms of pulmonary tuberculosis made it possible to postpone an emergency operation for a period of up to 2 weeks in all cases. For the prevention of aspiration pneumonia the bronchi were repeatedly cleansed in 8 patients and therapeutic lavage of the bronchi was carried out in 7 patients. PMID- 2271249 TI - [Respiratory biomechanics and the state of capillary blood flow in patients with fibrous-cavernous pulmonary tuberculosis before and after partial lung resections]. AB - The article discusses the results of studying the ventilation function of the lungs, biomechanics of respiration, and condition of the capillary blood flow in 36 patients with fibrous-cavernous tuberculosis before and after partial resection. In 69.4% of cases obstructive signs were attended by restrictive signs of deficient ventilation. The disorders of capillary blood flow corresponded to or were more extensive than the zone of affection demonstrated by roentgenography, which made it possible to determine the volume of the surgical intervention objectively. Signs of rigidity of the bronchopulmonary system prevailed in the early period after partial lung resection and deterioration of microcirculation was encountered. Restoration of the functional parameters and improvement of the capillary blood flow in the late-term follow-up period confirmed the efficacy of partial resections conducted in the early stage of complex treatment of patients with fibrous-cavernous pulmonary tuberculosis. PMID- 2271250 TI - [Effectiveness of therapeutic and surgical treatment after delayed detection of destructive pulmonary tuberculosis]. AB - The authors studied the results of antibacterial therapy in 647 and the results of surgical treatment in 837 patients. Complex modern antibacterial therapy led to recovery of only 65% of patients, in 20-25% of patients tuberculosis progressed with the formation of chronic forms, lethality was up to 13.0%. Timely undertaken surgical treatment after an ineffective course of antibacterial therapy facilitated stable recovery of 98% of patients with complete restoration of working capacity in 93.2%. PMID- 2271251 TI - [Urgent problems of diagnosis and treatment of reflux esophagitis]. AB - The authors analyse the results of diagnosis and surgical treatment of various forms of reflux esophagitis in 426 patients. The disease was caused by hiatal hernia in 60.4% of patients, by various operations on the cardia in 22%, and by gastric and duodenal ulcer in 8.2% of patients. Various diagnostic methods are evaluated, among which intraesophageal pH measurement and esophagofibroscopy are particularly important. The indications for operative treatment are formulated. Operations were carried out on 349 patients, complications occurred in 15%. The lethality was 0.6%. Nissen's fundoplication is the operation of choice. PMID- 2271252 TI - [Clinico-morphological evaluation of pathogenetic mechanisms of bouginage and intubation on cicatricial esophageal stenosis after chemical burns]. AB - The article deals with the clinico-morphological appraisal of bougienage and intubation of patients with cicatricial constriction of the esophagus after chemical burns. Endoscopic and morphological studies were carried out in 38 patients before and during treatment. Bioptic material collected from the esophageal mucosa was studied on a light-optic and ultrastructural level. The results of the study showed that bougienage of the epithelialized strictures causes protracted stimulation of intracellular regenerative processes and thus facilitates the development of leukoplakia of the squamous epithelium. The prevention of esophageal precancer in this case consists in radical maintenance bougienage and regular medical examination. Bougienage of ++non-epithelialized strictures stimulates the formation of young granulation tissue, while subsequent intubation stimulates reparative processes, creating in this manner conditions for adequate epithelialization of the ulcerated esophageal strictures. PMID- 2271253 TI - [Surgical treatment of myasthenia gravis in children]. AB - Thymectomy was included in the complex of therapeutic measures in the management of generalized myasthenia in 41 children. Much attention was given to preoperative management in which plasmapheresis was applied along with the traditional methods. As a result, maximum compensation of the myasthenic disorders was achieved and spontaneous respiration was restored in 9 patients who were given artificial ventilation of the lungs before the operation. The authors describe the techniques of thymectomy and the changes found in the thymus during histological study. No complications occurred. All of the children were discharged from the clinic in an improved condition. The late-term results were studied in 38 children in follow-up periods of 6 months to 4 years. Marked stable improvement was recorded in 31 (77.5%) patients. PMID- 2271254 TI - [Use of the greater omentum in thoracic surgery]. PMID- 2271255 TI - [Stage-by-stage surgical treatment of incompetence of bronchial stump and bronchial fistula after pneumonectomy in lung cancer]. PMID- 2271256 TI - [Left-side chylothorax in closed comminuted fracture of the IV thoracic vertebra]. PMID- 2271257 TI - [Problems of surgical treatment of dysfunction of heart valve prosthesis]. AB - The article generalizes experience in surgical treatment of disturbed functioning of heart valve prostheses. Functioning was impaired in 3.2% of 5113 prostheses. Operations were repeated in disturbed functioning of heart valve prostheses in 58 (35.4%) patients, in 7 of them the intervention was repeated twice. Closure of fistulas (26.2%) is possible only in moderate paravalvular+ insufficiency which is not connected with septic endocarditis. The authors emphasize the great risk of repeated operations, which calls for special attention to be paid to the prevention of disturbed functioning of heart valve prostheses. PMID- 2271258 TI - General practice training in the hospital. PMID- 2271259 TI - Validation of a method for the rapid diagnosis of urinary tract infection suitable for use in general practice. AB - A combination of reagent strip testing and examining urine appearance can be used to screen out noninfected cases before urine specimens are sent to the laboratory. A validation of this method was carried out in a microbiology laboratory using 970 specimens received over a three-week period. When the tests for nitrite, blood and protein on N-Multistix reagent strips (Ames) were all negative in a clear urine then the predictive value for the absence of bacteriuria was 98.5%. Positive strip tests in a turbid urine detected 80.1% of infections. On the basis of these findings it is recommended that general practitioners test the urine samples of all patients with suspected urinary tract infections by this method and only send to the laboratory those specimens with positive findings. Using this method the routine laboratory workload involved in testing urine specimens would be reduced by 40%, instant results would be available in the general practitioner's surgery and the patient would receive immediate and appropriate treatment. PMID- 2271260 TI - A study of microscopical and chemical tests for the rapid diagnosis of urinary tract infections in general practice. AB - Aids to the rapid diagnosis of urinary tract infection were assessed by the examination of 325 consecutive urine samples taken in the normal course of work in a general practice. Of these samples 103 produced a pure growth of at least 10(5) organisms per ml. The appearance and smell of each sample was noted and it was then tested by simple low-power microscopy of a drop of urine and by a dipstick which measured leucocyte esterase and nitrite, together with protein, blood and pH. In addition, pus cell counts per mm3 were performed on 272 of the samples using a cytometer chamber. This method is too time-consuming for routine use in the surgery. Neither a cloudy appearance nor haematuria were sufficiently specific to be of much use in the diagnosis of urinary tract infection. In the prediction of a 'positive' culture the sensitivity and specificity of the other tests were as follows: drop method microscopy 95% and 76%, respectively; cytometer count 95% and 81%; leucocyte-esterase estimation 89% and 68%; and nitrite 57% and 96%. These figures may underestimate the true values of the tests in the diagnosis of urinary tract infection because infection may be present in some cases producing growths of less than 10(5) organisms per ml. It is concluded that the most useful aid to the diagnosis of urinary tract infection is low-power microscopy of a drop of urine. PMID- 2271261 TI - An evaluation of the hospital component of general practice vocational training. AB - The contribution of the hospital component of vocational training to the needs of the future general practitioner was investigated by undertaking semi-structured interviews with a representative sample of doctors involved. The findings indicated that, in general, training was failing to address objectives perceived to be important for general practice by the study sample. Problems related to the context and style of hospital training also emerged, which appeared to be limiting the learning potential of this type of experience for general practitioner trainees. It is apparent that there is a need to clarify priority objectives for the hospital component of vocational training, and ensure that it provides the opportunity to achieve them. PMID- 2271262 TI - Acceptability of oxygen concentrators: the patient's view. AB - The impact of the installation of an oxygen concentrator on the lifestyle of 30 patients in two health districts has been investigated using a questionnaire. Marked improvements in general well-being (83% of respondents), breathing (82%), mobility (62%) and sleep pattern (52%) were reported. The long term nature of the aims of treatment were understood by 83% of the respondents and the mean period of time the patients used the concentrator was satisfactory. However, 34% of respondents had a concentrator with only one outlet and 70% had the concentrator situated in a commonly used room with the possibility of problems with noise. Thirty one percent of the respondents were still smoking. The recommendations given to patients for the sitting of the concentrator and the number of outlets should be improved. However, the oxygen concentrator was found to be generally well tolerated and this refutes criticism that patients may find it restricting. PMID- 2271263 TI - Hyperlipidaemia in general practice: three year follow up of an opportunistic screening project. AB - As part of the national lipid screening project 927 people with a plasma cholesterol level greater than 6.5 mM were detected by screening 4006 men and women aged 25-59 years. Three years later 801 of the 878 patients eligible for a follow-up study (91%) had been followed up at least once. The median number of follow-up visits was two. The bulk of the workload fell on the nursing staff. The mean decrease in cholesterol level was 8-14% in those receiving dietary advice only, 15-25% in those receiving additional drug treatment and 12% for all patients. A proportion of this decrease must be attributable to regression to the mean, loss to follow up when patients were doing well, and the patients' knowledge of their follow-up date. Data on a group of patients not attending for regular follow up suggest that regression to the mean could account for up to 7% of the cholesterol reduction observed. Screening for hyperlipidaemia in general practice is feasible when the necessary infrastructure is provided, but even with a fairly conservative protocol 3% of those screened received drug treatment. PMID- 2271264 TI - Experiences of patients with false positive results from colorectal cancer screening. AB - A survey was conducted to study the experiences of patients with false positive results for colorectal cancer. The study patients were participants in a randomized trial of compliance with different methods of colorectal cancer screening by faecal occult blood testing. Fifty four out of fifty six patients (96.4%) with false positive results agreed to be interviewed. An age and sex matched control group of 112 patients with negative test results was identified - 92 (82.1%) returned questionnaires. Thirteen of the patients with false positive results (24.1%) and 19 controls (20.7%) were to some extent distressed by the initial letter inviting them to participate in the screening programme. Thirty seven of the patients with false positive results (68.5%) felt some degree of distress at the initial positive test result and 19 (35.2%) some distress because of delays experienced in the process of being screened. Ten false positive patients had colonoscopy and the median waiting time for this procedure was 10 days--half of the patients found this wait distressing. Nevertheless, 53 of the patients with false positive results (98.1%) felt that it had been worthwhile to have had the test. Generally, colorectal screening was as acceptable to the patients who experienced false positive results as to those with negative results. PMID- 2271266 TI - Minor surgical procedures performed by general practitioners. PMID- 2271265 TI - Do our patients receive maximum benefit from preventive care? A North American perspective. AB - Politicians, their constituents and family physicians believe that preventive medicine is essential if health care is to be improved. Family physicians believe that the majority of their patients are well cared for with preventive health care services but in reality preventive services are provided to less than half the population and some to fewer than 10%. Barriers to providing preventive care include the selection of procedures of unproven effectiveness, public unawareness of the benefits of the procedure and practical obstacles for physicians providing the services. Assessment of each of these barriers indicates how preventive care can be improved. Narrowing the gap between what we believe about preventive care and the level of preventive services we are providing could improve the health of our nations. However, the concept of primum non nocere must dominate the assessment of currently advocated preventive procedures and the consideration of new procedures. PMID- 2271267 TI - Changing patterns of drug use and HIV infection. PMID- 2271268 TI - Use of defibrillators in general practice. PMID- 2271269 TI - Inflammatory cervical smears. PMID- 2271270 TI - Terminal care at home. PMID- 2271271 TI - Surveillance of the over 75s. PMID- 2271272 TI - Debate on euthanasia. PMID- 2271273 TI - Management of myocardial infarction in the community. PMID- 2271274 TI - Coronary heart disease: preventable but not prevented? PMID- 2271275 TI - The consultation and health outcomes. PMID- 2271276 TI - A study of communication between general practitioners and specialists. AB - A random sample of referral letters from general practitioners to outpatient departments of general medicine, dermatology, neurology, and gastroenterology at an Amsterdam teaching hospital were analysed together with the specialists' replies for 144 referrals. The pairs of letters were judged by a panel of four general practitioners and four specialists. Letters were assessed according to quality and content, clarity, request for return to general practitioner care, time intervals between referral and consultation and between consultation and the specialist's reply. The judges were also asked to assess whether in their opinion the letters were of value in teaching or were discourteous. Though in general intraobserver agreement on what constitutes a good letter was low, deficiencies were revealed in the quality of letters and there were delays in transmission and missed educational opportunities. PMID- 2271277 TI - General practitioner referral rates to district psychiatry and psychology services. AB - The number of referrals made to a district psychiatry service by each of the local general practitioners over a five year period was counted and a large variation in general practitioner referral rate was found. Ten referral letters from each of the general practitioners were independently assessed for the amount of detail included and a mean score for each general practitioner obtained. A significant negative correlation was found between referral rate and amount of detail in referral letters, that is low referrers wrote very detailed letters. The procedure was repeated over an 18 month period including referrals to the district psychology service. Referral rate to the psychologists was positively correlated with detailed referral letters, that is those who referred many patients to the psychologists wrote detailed letters. This study has indicated a wide variation in the use of the psychiatry and psychology services by general practitioners which cannot be explained solely on the basis of a general referral tendency. It is likely that constructive liaison between psychiatrists and general practitioners, especially those who refer a large number of patients, could enhance the care of patients with psychiatric disorder in general practice. PMID- 2271278 TI - Does awareness of being video recorded affect doctors' consultation behaviour? AB - Four general practitioners, two of whom had no previous experience of video recording in the consultation, took part in a study to assess the effect of awareness of video recording on their consultation behaviour. A video camera was sited unobtrusively in each consulting room for a month during which five randomly selected surgeries were recorded with the doctors being informed at the time, and five without their being informed. The video recorded consultations were analysed using TIMER, a tool designed to measure objectively behaviour in terms of physical, verbal and secondary activities in consultations. The proportions of time spent on the 27 consultation parameters were compared when doctors were aware and unaware of the recording, using analysis of variance. This demonstrated only one significant difference, in the low frequency parameter of the doctor's exploration of the patients' concepts (P less than 0.05). In a secondary analysis of the first four consultations in each surgery, where any effect of the presence of the video camera would be expected to be most marked, there was again only one significant difference in the 27 parameters (in patient preparation; P = 0.01). No significant difference owing to awareness of video recording was found in consultation length, the number of problems dealt with, or previous inexperience of video recording. When surgeries at the start of the month were compared with those at the end, four significant differences (P less than 0.05) out of 108 areas were demonstrated both when the doctor was aware and unaware of video recording, and there was no consistency in the direction of the differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271279 TI - A study of the presentation of somatic symptoms in general practice by patients with psychiatric disturbance. AB - A computerized questionnaire was used to collect information on the presentation of symptoms in all 125 new patients presenting to one general practitioner in the course of one year who were considered to be suffering clinically significant psychiatric disturbance. Comparison was made between the 73 (58%) patients presenting with psychological symptoms and the 52 (42%) patients presenting with somatic symptoms for which no physical explanation was evident at the time of the consultation. Important differences emerged between the groups. Those patients presenting somatic symptoms had lower scores on the tests of psychiatric distress (indicating severity), fewer individual symptoms and fewer severe symptoms than patients presenting with psychological problems. This group also had statistically significant differences in personality profile and reported significantly fewer social problems. Prognosis for both groups was similar in that patients in both groups were equally likely to have a normal psychiatric distress score after six months. Adequate management of somatizing patients calls for vigilance and for improved detection and negotiating skills. Reviewing the computer results with patients helped them discuss their symptoms and the system allowed the general practitioner not only a clinical assessment of these patients' problems but a measure of psychological, social and personality components. PMID- 2271280 TI - Professional relationships between general practitioners and pharmacists in health centres. AB - The inclusion of pharmacies in health centres has created opportunities for general practitioners to become better acquainted with the potential contribution of pharmacists to health care. A qualitative study has been made to explore the extent to which this potential has been realized. Ten health centres with an integral pharmacy were selected, one from each of the regional health authorities in England which had at least one such health centre. Interviews were conducted with 13 general practitioners and 10 pharmacists working in the health centres. Nine general practitioners working in health centres without pharmacies and 10 community pharmacists were also interviewed. General practitioners' attitudes towards health centre pharmacists appeared to differ markedly from the attitudes of colleagues working in relative isolation from pharmacists. It appears that general practitioners working closely with the pharmacist develop a collaborative approach to health care. PMID- 2271281 TI - Risk assessment in the prevention of coronary heart disease: a policy statement. Coronary Prevention Group. AB - Assessing an individual's risk of coronary heart disease should involve an examination of all the main risk factors in a setting where follow up advice and treatment is available if required. A selective approach to cholesterol testing is suggested and a range of recommendations are made for primary care workers and other health professionals, health authorities and government. This paper represents the consensus view of a wide range of bodies and it is intended to be the first in a series of publications on how to carry out risk assessment and provide consequent services. PMID- 2271282 TI - Fatal methaemoglobinaemia in a dental nurse. A case of sodium nitrite poisoning. AB - Methaemoglobinaemia may be caused by ingestion of a number of drugs, among them nitrites, some of which are remarkably toxic. This was tragically highlighted by the death of a 17 year old dental nurse after taking a single 1 g tablet of sodium nitrite. These tablets are widely used in the medical and dental profession to prevent rusting of instruments while immersed in disinfectant solutions. The toxicity of this chemical should be more widely recognized and its storage made correspondingly more secure. Methaemoglobinaemia should be considered as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause. PMID- 2271283 TI - Postnatal depression: a review of recent literature. AB - Depression affects 5-22% of women after childbirth. Some women with postnatal depression will experience a prolonged or relapsing illness that may last until their children enter school. It has adverse effects upon the coping abilities of women, their relationships with their infants, partners and social networks and may adversely affect the educational attainment and behaviour of their children. Since many more women are now active in the workforce, the effects of postnatal depression have obvious economic consequences both for their families and their employers. This article discusses the association between depression and the puerperium and reviews the evidence for vulnerability factors that may make a woman prone to depression. It is suggested that women with, or vulnerable to, postnatal depression can be identified and helped. PMID- 2271285 TI - Appointing counsellors in general practice. PMID- 2271284 TI - Health education: using a video in general practice. PMID- 2271286 TI - Complementary and allopathic cooperation. PMID- 2271287 TI - Research for all in general practice. PMID- 2271288 TI - Budget holding. PMID- 2271289 TI - Orchitis in chicken pox. PMID- 2271290 TI - [Acute abdomen caused by spontaneous rupture of splenic hydatid cyst]. AB - We report a rare case of acute abdomen caused by the spontaneous rupture of a splenic hydatid cyst into the abdominal cavity, causing a massive hemoperitoneum due to accompanying rupture of the spleen which required splenectomy. A review is made of the literature on this rare entity, its treatment and its consequences and their prevention and treatment. PMID- 2271291 TI - [Phytobezoar and cellulase treatment]. PMID- 2271292 TI - [Jean Faget and the first rectal resection]. PMID- 2271293 TI - [Ogilvie syndrome. Is it a digestive motility disorder?]. PMID- 2271294 TI - [Carcinoma of the esophagus. Palliative treatment with endoscopic prosthesis]. AB - The efficacy and safety of endoscopically inserted esophageal prosthesis was evaluated in 33 patients with non-operable carcinoma involving the esophagus. In 30 cases, the origin of the tumor was esophageal, and in 3 cases, bronchopulmonary. Esophago-pulmonary fistula was present in 9 patients. Histologic exam of the tumors revealed 11 adenocarcinomas and 22 epidermoid carcinomas. In every case, Atkinson prosthesis was used and previous esophageal dilatation was needed in 21 patients. Normal oral feeding was achieved in 29 patients. Mean hospital stay after insertion of the prosthesis was 5 days. Survival rate was 84.8% at one month, 63.6% at 4-6 months, 42.4% survived more than 6 months, and 21.2% were still alive one year after the procedure. Complications occurred in 3 patients (9%) -esophageal perforation in two cases, and pneumonia in one case. One patient died. In conclusion, in patients with advanced carcinoma involving the esophagus, palliative therapy with endoscopically inserted esophageal prosthesis is effective, relatively safe and cheap. PMID- 2271295 TI - [Evolution of stomach cancer mortality in Spain (1951-1985)]. AB - A descriptive study was made of the trend of the stomach cancer mortality rate in Spain over the period 1951-1985. An upward trend was observed until 1963, and from that time on it gradually decreased in both sexes, though the male population always had a higher rate. By age, the mortality rate showed a clear increase in the fifties, in both sexes. A cohort effect was also clearly evident, the mortality rate was gradually lower in the most recent generations and among the different age groups, which is in keeping with the gradual decrease of the "Potential years in life lost" throughout the time period investigated. The above descriptive data would doubtless be of interest should analytical studies be undertaken. PMID- 2271296 TI - [Long-term study of gastroduodenal ulcer perforation]. AB - One hundred forty-four patients, peptic (129 males and 15 females) treated for peptic ulcer perforation between 1972 and 1988 were reviewed. All were treated surgically, and in 28 the ulcer was also treated. The mean perforation time before treatment was 14 +/- 12.3 hours. The immediate postoperative results and long-term evolution were evaluated on the basis of the medical history, follow-up check-ups and home questionnaires. The were post-operative complications in 33 (23%) of the 137 patients who survived surgery; there was no difference in morbidity between the group in which only Closure and Epiploplasty (group C + E) were performed and group CD, where some type of definitive surgery was added, although the seven deaths belonged to the former. Of the 104 patients who were evaluated on a long-term basis (follow-up period of 55 +/- 44 months), poor results were obtained in 58 of the 82 belonging to group C + E and in four of the 28 in group CD, with a total of 13 re-operations (12 and one, respectively). Only a previous ulcer history dating from over three months had any effect on the appearance of recurrences in group C + E. We recommend performing a VGP within the first six hours as the preferred technique for pyloric or juxtapyloric perforations in patients with a previous ulcer history exceeding three months, since the rate of cure is satisfactory and there are few if any complications. PMID- 2271297 TI - [Natural killer (NK) cells and interleukin 2 (IL-2) in Crohn disease]. AB - An analysis was made of spontaneous Natural Killer (NK) activity, the proportion of NK cells and Interleukin 2 (IL-2) production in response to a phytohemagglutinin (PHA) using isolated mononuclear peripheral blood cells from 27 patients with Crohn's disease (CD) and 27 healthy controls. The results obtained showed a decrease in NK activity in comparison with the control group (p less than 0.05), occurring mainly in patients in whom the disease was in an active phase (p less than 0.005), with no apparent relationship to the proportion of NK cells. IL-2 production was, however, similar to that of the healthy controls. A positive correlation between spontaneous NK activity and IL-2 production was evident. The origin of these findings is controversial, suggesting that other factors with a negative modulating effect may inhibit NK function. PMID- 2271298 TI - [Spontaneous bacterial peritonitis: a comparative study of 2 methods of ascitic fluid culture]. AB - The sensitivity in the diagnosis of spontaneous bacterial peritonitis of ascitic fluid inoculation in blood culture bottles has been compared with the conventional method. We have analyzed 74 positive ascitic fluid cultures from 64 patients, the samples being processed by both techniques simultaneously. While all the ascitic fluid cultures performed by inoculation in blood culture bottles were positive, in only 42 from the 74 conventional cultures (56, 75%) bacterial growth was detected (p less than 0.001). Nineteen bacterascites were diagnosed by inoculation in blood culture bottles and 10 by the conventional method (p = NS). Gram stain was only positive in 3 spontaneous bacterial peritonitis (6%). We conclude that ascitic fluid inoculation in blood culture bottles improves significantly the sensitivity of the microbiological diagnosis of spontaneous bacterial peritonitis, without increasing the diagnosis of bacterascites. PMID- 2271299 TI - [Neurophysiology of gastrointestinal pain]. AB - The only non-general sensation that can be elicited from the gastrointestinal (GI) tract is that of pain, which can go from slight discomfort to severe pain. However, in certain parts of the intestine, such as the rectum and gastroesophagus, the sensation of pain can be preceded by a non-painful sensation of distension at low levels of stimulation. GI pain is often dull, poorly defined and difficult to pinpoint. In some cases, GI pain is projected to areas of the body distant from the source organ ("referred" pain). These characteristics indicate that the representation of internal organs within the nervous system is very imprecise. Experimental evidence based on behavioral, neurological and clinical testing shows that most GI pain is the result of activity in afferent visceral sensory fibers contained in sympathetic nerves, and that the afferent intestinal innervation by means of parasympathetic nerves is not essentially related to GI pain signalling and transmission. As for the peripheral sensory receptor coding mechanism in the intestine, experimental tests have shown the existence of specific visceral nociceptors in certain places (e.g., the biliary system) and the existence of a king of non-specific "intensity" receptors in others (e.g. the colon). In any case, the number of afferent nociceptive fibers in the intestine is minimal, and this accounts for the fact that large areas of the GI tract appear to be insensitive or to require considerable stimulation before pain can be elicited. The few afferent nociceptive fibers contained in the sympathetic nerves can excite quite a few second order neurons in the medulla spinalis, which in turn generate an extensive divergence within the medulla spinalis and brain stem, including at times long supraspinal branches. This divergent input can activate different motor, autonomous and sensory systems, thus triggering the general reactions which characterize visceral nociception: diffuse pain which is difficult to pinpoint, referred at times to somatic areas, and autonomous and somatic reflexes resulting in prolonged motor activity. PMID- 2271300 TI - [Cavernous hemangioma of the esophagus]. AB - Hemangiomas are benign tumors and their esophageal location is extremely rare. Identification prior to surgery is very important in order to spare the patient unnecessary resections. We report one case treated by localized surgical removal. PMID- 2271301 TI - [Primary malignant melanoma of the esophagus]. AB - Primary malignant melanoma of the esophagus is very rare, and only 139 cases have been described in all the world literature. We present one case of primary malignant melanoma of the esophagus in a 76-year-old woman who reported the symptoms of dysphagia and recent weight loss; the radiography showed a large polypoid mass filling the entire lower half of the esophagus, dark brown-black in the endoscopy. Histologic analysis demonstrated the existence of a malignant melanoma infiltrating the esophageal mucosa, composed of anaplastic cells with abundant brown pigment which had positive immunoreactivity for the S-100 protein. PMID- 2271302 TI - [Aorto-duodenal fistula: endoscopic diagnosis]. AB - We report the case of a patient with hemorrhage due to secondary Aortoenteric Fistula (AEF), diagnosed by emergency oral endoscopy. We stress the importance of early diagnosis in these patients by virtue of a so-called "warning hemorrhage", which usually occurs hours or weeks before the appearance of a massive hemorrhage which is soon fatal. The importance of emergency endoscopy in the early diagnosis of these cases is emphasized. PMID- 2271303 TI - [Adenocarcinoma at the site of colostomy. Is it local recurrence or subsequent cancer?]. AB - This paper presents on case of adenocarcinoma at the site of colostomy in a patient treated by abdominoperineal amputation five years earlier due to rectal cancer. The case raised the doubt as to whether the carcinoma represented a late, local recurrence or a second metachronic neoplasia. The most frequent location and pathogenesis of each were analyzed. The role of follow-up of these patients in detecting cases such as the one presented here are discussed. PMID- 2271304 TI - Asthmatic reaction to PMMA. PMID- 2271305 TI - Third molar wisdom. PMID- 2271306 TI - Discrimination against men. PMID- 2271307 TI - Working conditions of resident SHOs. PMID- 2271308 TI - Clinical evaluation of three posterior composite and two amalgam restorative materials: 3-year results. AB - The clinical performance of three posterior composites and two amalgams was evaluated over 3 years. Three hundred and nine composites and 200 amalgams were reviewed at the 3-year recall. The following parameters were assessed: fractures, gingival condition, interproximal contacts, marginal adaptation, staining and colour match. Although there was no significant difference in the overall failure rate between the two types of material, there was a significantly higher incidence of fracture in the amalgam restorations. The amalgam failures were exclusively mechanical, whereas those affecting composites also included failures that were more biological in nature. A significantly higher proportion of the Class II composites failed to achieve an adequate approximal contact, but this was not reflected in a more adverse gingival response. Colour match, surface and marginal stain varied significantly within the composite group and appeared to be material-related. Overall, the materials Occlusion and P-30 were considered to be performing adequately. The clinical handling, colour match and radiopacity of Clearfil Posterior were considered to be unsatisfactory. PMID- 2271309 TI - Combining commercial, Health Boards' and GDPs' sponsorship in an effort to improve dental attendance for young school leavers. GPDs' involvement and opinion. AB - Using a telephone survey technique, general dental practitioners' opinions and involvement in a dental health campaign were examined. The campaign was planned and organised by the Forth Valley Health Board Community Dental Service. The objectives of the campaign were to promote regular dental visits and oral health awareness among 15-18-year-old schoolchildren. The campaign linked commercial sponsorship with Health Board financing. The majority of the GDPs were positive towards the campaign and engaged enthusiastically in the activities suggested by the campaign organisers. Although there was a subjective feeling of disappointment regarding the uptake of dental services by new patients, 85% of the GDPs were in favour of similar annual campaigns. PMID- 2271310 TI - Resistance to local analgesia--report of a case treated using 5% lignocaine solution. AB - A case is described of a patient who appeared to belong to the category labelled 'resistant' to local analgesia, in whom use of a 5% lignocaine solution with 1 in 100,000 adrenaline allowed painless routine dental treatment to be carried out. A discussion of the case, and the various other opinions which were considered for management, are presented. PMID- 2271311 TI - Recognition of oral lesions of HIV infection. 2. Hairy leukoplakia and Kaposi's sarcoma. PMID- 2271312 TI - Keeping your staff. Part 2. Performance related pay in practice. AB - Staff are one of the greatest assets a practice has, and effective communication and motivation is rewarding for all parties. Three years ago Charles Scola and his partners introduced a performance related pay (PRP) scheme into their busy general dental practice. Here, he discusses the resulting benefits and also some of the teething problems they have encountered. PMID- 2271313 TI - A standard way to measure pain and psychological morbidity in dental practice. AB - Dental surgeons are continually faced with patients in pain. In complicated cases, a measure of pain and its psychological consequences are essential. The McGill Pain Questionnaire measures pain using 78 descriptors and is useful not only in diagnosis but in monitoring treatment outcome. The Hospital Anxiety and Depression Scale is a simple way of assessing anxiety and depression in non psychiatric out-patient clinics. These two scales are compared with other measures that can be used. PMID- 2271314 TI - [ADP in the hospital. We promote careful consideration of training in ADP!]. PMID- 2271315 TI - [ADP in home care nursing. We continually discover new ways to use the system]. PMID- 2271316 TI - [ADP in patient classification. Patient classification--suited to electronic data processing]. PMID- 2271317 TI - [ADP in the NSF. Norwegian Nurses' Association and data technology]. PMID- 2271318 TI - [Pharmacology (3). Different antibiotics]. PMID- 2271319 TI - [Preventive health care. Early detection of hearing loss in children. A challenge to health services]. PMID- 2271320 TI - [Kristansand's nursing college. Matters in rehabilitation. Interview by Kjell Arne Bakke]. PMID- 2271321 TI - [ADP and personal protection. Need for safe information processing]. PMID- 2271322 TI - [ADP in the nursing home. Who eats what? Diet in data information]. PMID- 2271323 TI - [Nursing 2010. Norwegian Nurses' Association]. PMID- 2271324 TI - [Development of competence among nursing personnel]. PMID- 2271325 TI - [Seasonal position--a new management model]. PMID- 2271326 TI - [Accomplishing seasonal positions]. PMID- 2271327 TI - [Improved patient care with greater competence. Conversion of nursing assistants' positions into nurses' positions]. PMID- 2271328 TI - [Pharmacology (4). More on antibiotics]. PMID- 2271329 TI - [Utilization of hospitals and community health services by the elderly--an analysis]. PMID- 2271330 TI - [Open, resource-oriented care plans]. PMID- 2271331 TI - [Trial with a new anti-nausea regime]. PMID- 2271332 TI - [University news from Tromso. Full degree study in nursing science]. PMID- 2271333 TI - [Nursing research--focus on the relationship between practice and theory]. PMID- 2271334 TI - [Pharmacology (5). The oldest drugs. From antiquity onward to the age of enlightenment]. PMID- 2271335 TI - [Refugee psychiatry and the role of nurses]. PMID- 2271336 TI - [A study of home nursing and medical services in the community. Content, accessibility and team work in home care services]. PMID- 2271337 TI - [How the past shapes the future. The role of tradition in the nursing profession]. PMID- 2271338 TI - [Establishment of a protected unit--a practical formula]. PMID- 2271339 TI - Restenosis after angioplasty. PMID- 2271340 TI - A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction. AB - The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state. PMID- 2271341 TI - Excess purine degradation caused by an imbalance in the supply of adenosine triphosphate in patients with congestive heart failure. AB - To evaluate purine degradation in patients with congestive heart failure concentrations of serum hypoxanthine, lactate, and noradrenaline were measured before and after submaximal treadmill exercise in 12 patients with chronic congestive heart failure and nine healthy volunteers. In four patients the concentration of hypoxanthine was significantly higher than in the controls or in the remaining eight patients with congestive heart failure. Venous lactate and noradrenaline in the four patients with high concentrations of hypoxanthine were also significantly higher than those in the eight patients with normal concentrations of hypoxanthine. Patients who responded normally were also more likely to have been treated with vasodilators and angiotensin converting enzyme inhibitors. Exercise induced arrhythmias were more common in the patients with high concentrations of hypoxanthine. These results suggest that the excess purine degradation in patients with congestive heart failure might be the result of a "relative" disturbance in the supply of adenosine triphosphate caused by the shift of cellular metabolism from aerobic glycolysis to anaerobic glycolysis during submaximal exercise and that hypoxanthine (a substrate for xanthine oxidase and a source of free radicals) was increased after submaximal exercise in some patients with congestive heart failure. PMID- 2271342 TI - Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography. AB - Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult. Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning. Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence. Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole. The myocardium was divided into nine segments for direct comparison of perfusion with wall motion. Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion. After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects. The site of wall motion deterioration was always the site of a reversible thallium defect. Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging. There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole. There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments. In nine patients the change was apparent visually and it was maximal in the subendocardial region. Magnetic resonance imaging of reversible wall motion abnormalities in patients with coronary artery disease is feasible during pharmacological stress with dipyridamole and may be associated with a reduced magnetic resonance signal. The failure to show wall motion abnormalities in all cases of reversible thallium defects may be because the defect was small or because dipyridamole caused perfusion defects in the absence of myocardial ischaemia. PMID- 2271343 TI - A controlled trial of community based coronary rehabilitation. AB - Two hundred patients who had suffered an acute myocardial infarction 4-6 weeks before entered a randomised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner. Eighty one per cent of the treatment group continued to exercise until they returned to work and 73% completed three months' exercise. There were no serious complications of the exercise course. The prevalence of angina pectoris fell by 10% in the treatment group but rose by 60% in the control group. The perceived energy level rose by significantly more in the treatment group than in the controls. The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product (a reflection of myocardial workload) at peak exercise. Coronary rehabilitation in the community can be both safe and effective. PMID- 2271344 TI - Changes in the electrocardiographic response to exercise in healthy women. AB - Changes in the P wave, QRS complex, ST segment, and T wave during and after maximal exercise were quantitatively analysed in 116 healthy women with a mean age of 39. The corrected orthogonal Frank lead electrocardiogram was continuously recorded and computer processed during bicycle ergometry. With exercise, maximal spatial P wave vectors shifted downward. The Q wave amplitude became more negative and the R wave amplitude diminished considerably in leads X and Y: the S wave amplitude decreased only slightly in these leads. The QRS vectors shifted towards right and posteriorly during exertion and a further shift in the same direction was seen in the recovery period. The ST segment amplitude 60 ms after the J point decreased with exertion and became negative at heart rates above 140 beats per minute, in particular in lead Y. ST segment depression increased with age. The T wave amplitude decreased during exercise and increased sharply in the recovery period. Though mean R wave amplitude in leads X and Y became more negative with exercise, this response was unpredictable in individual women. The exercise induced changes in QRS vectors in women resembled those described in men. Changes in the amplitude of the R wave should not be used for the diagnosis of coronary disease in women. ST segment depression was more pronounced in the inferiorly oriented lead Y than in lead X but it was unrelated to changes in the QRS vectors in these leads. PMID- 2271345 TI - Increase in native valve endocarditis caused by coagulase negative staphylococci: an Anglo-French clinical and microbiological study. AB - Native valve endocarditis caused by coagulase negative staphylococci has become more common. A study of 35 cases showed that the infections were usually acquired in the community and occurred in men (mean age 51 years). A pre-existing cardiac abnormality (mitral leaflet prolapse in a third of patients) was detected in 26 (74%). The source of the organisms in the community acquired infections was assumed to be the skin, though lesions were seldom demonstrated; most hospital acquired infections resulted from intravenous devices. Community acquired organisms were usually sensitive to penicillin, whereas those acquired in hospital were often multiresistant. Most infections were caused by Staphylococcus epidermidis. The frequency of acute presentation (26%) and of major neurological abnormality (23%), together with the need for valve replacement (often emergency) (51%) and the mortality (36%) suggest that coagulase negative staphylococci can be virulent aggressive pathogens, mimicking Staphylococcus aureus. PMID- 2271346 TI - Anomalous subaortic position of the brachiocephalic vein (innominate vein): an echocardiographic study. AB - In 24 (0.98%) of 2457 patients with congenital heart disease the brachiocephalic vein was in an anomalous position below the aortic arch. This is a much higher proportion of such cases than reported so far. This high frequency may arise from differences in the study population and the method of diagnosis. This venous anomaly was more common in patients with tetralogy of Fallot or ventricular septal defect with pulmonary atresia. Patients with the venous anomaly were more likely to have a right aortic arch. The anomalous course of the brachiocephalic vein from the neck to the junction of the superior vena cava was shown by cross sectional echocardiography. In doubtful cases, Doppler study usually clarified the anatomical arrangement. PMID- 2271347 TI - Circadian variation of heart rate is affected by environment: a study of continuous electrocardiographic monitoring in members of a symphony orchestra. AB - Twenty four hour ambulatory ST segment monitoring was performed on 48 members (43 players and five members of the management/technical team) of the British Broadcasting Corporation (BBC) symphony orchestra without a history of cardiac disease. This period included final rehearsals and live performances (for audience and radio) of music by Richard Strauss and Mozart at the Royal Festival Hall (n = 36) and Rachmaninov and Tchaikovsky at the Barbican Arts Centre (n = 21). During the period of monitoring one person (2%) had transient ST segment changes. Mean heart rates were significantly higher during the live performances than during the rehearsals. Mean heart rates during the live performance of Rachmaninov and Tchaikovsky were significantly higher than during Strauss and Mozart in those (n = 6) who were monitored on both occasions. Mean heart rates in the management and technical team were higher than those of the players. The recognised circadian pattern of heart rate, with a peak in the morning waking hours, was altered similarly during both concert days, with a primary peak occurring in the evening hours and a lesser peak in the morning for both musicians and management/technical staff. This study showed that environmental factors are of primary importance in defining the circadian pattern of heart rate. This has important implications when identifying peak periods of cardiovascular stress and tailoring drug treatment for patients with angina pectoris. PMID- 2271348 TI - Patients' observations of bioprosthetic valve failure: "my heart is honking, doctor". AB - Audible cardiac murmurs are uncommon and may indicate severe native valve dysfunction. In six patients with bioprosthetic mitral valves audible honking systolic murmurs suddenly developed. Doppler echocardiography showed characteristic striated regurgitant signals. At operation each prosthesis had torn cusps. New audible murmurs and striated Doppler signals originating from mitral bioprosthetic valves are indicators of cusp tears. Recognition of this is important because early detection of prosthetic valve dysfunction may improve subsequent surgical outcome. PMID- 2271349 TI - A new method of haemodynamic assessment of mitral stenosis in atrial fibrillation: construction of a nomogram. AB - Accurate haemodynamic assessment of mitral stenosis by hydraulic formulas requires measurement of the mean valve gradient and the cardiac output. The calculation is laborious, particularly in the presence of atrial fibrillation when averaged values obtained from multiple beat-to-beat determinations must be used. The relations between valve area, end diastolic gradient, and heart rate in 20 patients with mitral stenosis and atrial fibrillation were examined. In each patient the end diastolic pressure gradient for each cardiac cycle was related linearly to the RR interval of that cycle, and this relation was unchanged on exercise. The slope (S) and intercept (I) of this relation correlated with the degree of mitral stenosis as measured by the Gorlin valve area. The regression equations describing these relations were then used to construct a nomogram relating end diastolic pressure gradient to mitral valve area at different heart rates. When the nomogram was applied to catheterisation data from a further 30 patients the results correlated well with direct calculation of valve area by the Gorlin formula. The nomogram is simple to use, does not require measurement of cardiac output, and is independent of heart rate so that it is unnecessary for the patient to exercise during catheterisation. PMID- 2271350 TI - Acute pulmonary oedema on the Ruwenzori mountain range. AB - A 40 year old man had an episode of severe pulmonary oedema at 4000-5000 m during the ascent of the Margherita peak (5109 m) of Mount Stanley on the Ruwenzori. He had taken acetazolamide and high dose dexamethasone to treat symptoms of acute mountain sickness. Six years before he had been studied by right heart catheterisation as a healthy volunteer during hypoxic breathing at sea level. His pulmonary vascular reactivity had been within the normal range for 32 healthy subjects. This man had high altitude pulmonary oedema despite currently recommended treatments for acute mountain sickness and normal pulmonary vascular reactivity to hypoxia at sea level. PMID- 2271351 TI - Glossopharyngeal neuralgia associated with cardiac syncope: long term treatment with permanent pacing and carbamazepine. AB - Glossopharyngeal neuralgia associated with cardiac syncope developed in a 53 year old man. Symptoms were controlled with temporary and permanent transvenous pacing and carbamazepine. PMID- 2271352 TI - Rapid histological changes in endomyocardial biopsy specimens after myocarditis. AB - The course and response to treatment in acute lymphocytic myocarditis are conventionally monitored by endomyocardial biopsy performed every 3-12 weeks. A patient with a short history (five days) of acute myopericarditis of unknown aetiology presented in cardiogenic shock with evidence of severe systolic dysfunction on the echocardiogram. The initial biopsy specimen showed histologically unequivocal myocarditis. Repeat endomyocardial biopsy after four days of treatment with steroids and azathioprine showed substantial histological improvement, a reduction in cellular infiltrate and myocardial necrosis, and interstitial fibrosis. Serial biopsies at 2 weeks and then 1, 2, 4, 5, 8, and 14 months after the initial biopsy showed progressive clearing of cellular infiltrate, increasing interstitial fibrosis, and compensatory myocyte hypertrophy by 4 months. At 14 months scattered lymphocytes persisted but myocyte abnormalities had resolved completely. The patient remained symptom free and systolic function was normal during this recovery period. Early endomyocardial biopsy (within one week of diagnosis) may yield useful histological information on the response to treatment in patients with myocarditis. It may not be necessary to wait the customary 3-4 weeks to repeat the biopsy. This case shows the chronology of histological changes and emphasises that a return to normal myocardial function may precede resolution of the histological abnormalities, which may persist in part or may resolve totally after the acute episode. PMID- 2271353 TI - The electrocardiogram does not reliably reflect the (anatomical) transmural extent of myocardial infarction. PMID- 2271354 TI - Time of occurrence, duration, and ventricular rate of paroxysmal atrial fibrillation: the effect of digoxin. PMID- 2271355 TI - Aged-onset Kienbock's disease. AB - Kienbock's disease with onset after 50 years of age was studied. Of 127 patients with Kinebock's disease seen over the past 30 years, the cases of 15 (12 female, 3 male) were analyzed. The average age of onset was 58.3 years. Five specimens were obtained operatively in which necrosis of the lunate bone mixed with empty lacunae was identified, as was bony remodelling. Ulnar variance in the aged diseased group (group A) was smaller than that of the aged control group (group C). Moreover, it was noteworthy that the variance among aged controls (group C) was higher than among the young controls (group D). The metacarpal index of the patients with aged-onset Kienbock's disease was markedly lower than that of the young. Considering the increase of ulnar variance with age, the persistence of minus variance and the presence of osteoporosis might make the lunate bone susceptible to injury. PMID- 2271356 TI - The APS knee joint prosthesis. A review of 32 patients. AB - First clinical and radiographic results with a new knee joint prosthesis, implanted without cement, are reported and the characteristics of the implant (dowel fixation and special instrumentation) presented. The first series of 35 joints with a follow-up period of 1-3 years shows excellent results. Radiographically, primary osseous integration cannot be positively identified in all cases, but it could be proved in most instances. Cement-free implantation requires good preoperative bone quality and an operative technique which inserts the implant anatomically. If these two conditions are met, there is every probability of successful implantation. No problems specific to the implant have been encountered. PMID- 2271357 TI - Absorbable polyglycolide pins in fixation of displaced fractures of the radial head. AB - In a prospective study 24 patients with a displaced fracture of the radial head were treated by open reduction and internal fixation using absorbable polyglycolide pins, 2 mm in diameter. All patients admitted with fractures involving a quarter or more of the radial head, whether comminuted or not, were included in the study whenever there was a displacement of 2 mm or more between the fragments. The mean follow-up time was 28 months (range 15-43 months). A postoperative redisplacement of 1-3 mm between the fragments was seen in four patients with severely comminuted fractures. A transient inflammatory reaction around the implants occurred in two cases 8-12 weeks postoperatively. The functional end-result was classified as excellent or good in 22 patients (91%). This study indicated that successful fixation of displaced fractures of the radial head can be accomplished by using absorbable pins. PMID- 2271358 TI - Fracture incidence and bone mineral density of the distal radius in Japanese children. AB - The incidence of fractures of the distal radius in Japanese persons under 20 years of age was determined, and the bone mineral density of the radius was measured in 236 healthy Japanese children. The peak incidence of fractures occurred at 13 years of age (807 per 100,000) in boys and at 11 (300 per 100,000) in girls. Bone mineral density increased with age, but the rate of increase was not equal at the metaphysis and the diaphysis in the parapubertal period. The metaphyseal/diaphyseal ratio of bone mineral density was lowest at the age of 12 13 years in boys and 11 years in girls. The age at the peak incidence of fractures thus coincided with the age at which the metaphyseal/diaphyseal density ratio was lowest. Thus, it is suggested that low bone mineral density at the metaphysis may be the cause of the high incidence of these fractures in adolescence. PMID- 2271359 TI - Blood levels of active metabolites of vitamin D3 in fracture repair in humans. A preliminary report. AB - Blood levels of the active metabolites of vitamin D3, 25-hydroxycholecalciferol [25(OH)D3], 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 24,25 dihydroxycholecalciferol [24,25(OH)2D3] were determined in seven patients. Two subjects suffered from delayed union of tibial fractures; one showed a delayed union after a proximal tibial osteotomy; one patient suffered from bilateral femoral neck fractures, of which one failed to unite and the other united late; two patients had multiple fractures that united normally; and one patient exhibited staged bilateral femoral neck fractures whose occurrence was separated by a short interval and which united without undue delay. The blood levels of 25(OH)D3 were within the normal range. A relative decrease in 24,25(OH)2D3 values was noted in all patients, whereas in three subjects the decrease was absolute, to non-detectable levels. A decrease in 1,25(OH)2D3 levels was noted in only two patients. We postulate that these changes reflect the consumption of these metabolites during healing at the fracture site. PMID- 2271360 TI - The polymorphonuclear leukocyte: has it a role in fracture healing? AB - The aim of the present study was to assess whether the presence of polymorphonuclear leukocytes in the first stage of fracture repair was of any importance. In anesthetized male Wistar rats, a transverse osteotomy was performed at midshaft in one femur and immediately stabilized by an intramedullary Kirschner nail. The animals were allowed unprotected weight bearing immediately. Nine animals were made neutropenic before operation by injection of a specific rat polymorphonuclear leukocyte antiserum (antineutrophil serum, ANS) raised in sheep. The number of circulating polymorphonuclear leukocytes were kept below 20% of their normal value for 72 h postoperatively by intraperitoneal injections of ANS every 12 h. Control animals were injected with the same amount of normal sheep serum (NSS). All animals received cefuroxime (100 mg/kg day) concomitantly with the ANS injections. Six weeks after operation the animals were killed, the amount of callus formation was measured, and the bones were radiologically examined. The nails were then removed and both the healing fractures and the nonoperated femurs mechanically tested for bending. There were no differences in the amount of callus measured or in radiological healing. However, there was a significantly higher bending moment in femurs from animals treated with ANS than in those given NSS (P less than 0.02). No differences were observed in rigidity or total energy absorption. PMID- 2271361 TI - Influence of bone and soft-tissue operations on serum concentrations of growth hormone, somatomedin C and alkaline phosphatase. AB - After animal experiments suggested there was an interaction between growth hormone and bone healing, our aim in this paper was to ascertain whether there were any changes or possible interaction between the serum level of growth hormone, somatomedin C and alkaline phosphatase while a fractured bone was healing. To this end, the serum concentrations of growth hormone, somatomedin C, alkaline phosphatase and calcium were ascertained both pre- and post-operatively in two groups of patients--one with bone operations, the other with soft-tissue operations--and the results were compared. Comparing the groups, we found that after bone operations there was no increase in the serum level of growth hormone, nor of somatomedin C. An increase would have implied that these two hormones are directly involved in bone regeneration. There was no change in the serum level of alkaline phosphatase or calcium after either bone or soft-tissue operations. PMID- 2271362 TI - Surgical treatment of Jones fractures. AB - A transverse fracture of the proximal part of the fifth metatarsal is rarely caused by direct trauma but is usually secondary to overload. These fractures, when treated conservatively, have a high recurrence rate and give rise to prolonged sporting inactivity. The clinical and radiographical difference between an acute versus a stress fracture will decide on further treatment. A reversed graft, by an asymmetrical trapezoid autograft, offers a simple and effective surgical solution for nonunion and delayed union of Jones fractures in sportsmen. PMID- 2271363 TI - Kinematics of the patellofemoral joint. Investigations on a computer model with reference to patellar fractures. AB - Patellofemoral kinematics were studied on a computer model. The articulating point of the patella moves from distal to proximal during flexion, until the quadriceps tendon starts to turn around the femur tendo-femoral gliding. The pattern of patellofemoral movement consists of a gliding and rolling component, the latter at its maximum at the beginning of flexion. The pathway of the instant centers of motion moves from dorsal to ventral during flexion. Stress analysis shows that the contact area is at all times the area of maximum bending stress. The distal part of the patella is the part with mechanical stress at all angles of flexion. The conclusions to be drawn for treatment are that fractures within the proximal and central part of the patella need a very high stability of internal fixation, the distal part of the patella less so. Postoperative treatment must take into account the changing contact area, because the peak stress is always at the contact area. PMID- 2271364 TI - Massive wear of a steel ball head by ceramic fragments in the polyethylene acetabular cup after revision of a total hip prosthesis with fractured ceramic ball. AB - The purpose of this case study of severe metallosis is to draw the attention of orthopedic surgeons to extremely serious results of this kind in the event of the fracture of the ceramic ball in a total hip prosthesis. Eleven months after implantation of a KJF hip prosthesis with an aluminum oxide ceramic ball in combination with a polyethylene acetabular cup, fracture of the ceramic ball was observed. After examining the polyethylene cup during the revision operation, the operating orthopedic surgeon merely replaced the fractured ceramic ball with a metal ball head made of stainless steel. Twenty-five months after this procedure, radiography revealed massive wear of the steel ball head with resulting severe metallosis of the surrounding tissues. All prosthetic components therefore had to be removed. Careful examination of the removed prosthetic components clearly showed that sharp-edged ceramic particles originating from the fractured ceramic ball had become embedded in the bearing surface of the polyethylene cup. These tiny ceramic fragments, ranging from 0.05 to 2 mm, were too small to be seen by the operating surgeon's unaided eye. It is these extremely hard ceramic fragments that were responsible for the massive wear of the steel ball head, the hardness of which is approximately ten times less than that of aluminum oxide ceramic. The fracture of the ceramic ball further resulted in damage to the metal taper of the stemmed femoral component. In cases of this kind it is consequently absolutely essential to remove both the polyethylene cup and the ball head, and--if necessary--the femoral component as well. PMID- 2271365 TI - Brachial artery injury in closed elbow dislocation. Case report and review of literature. AB - A case of elbow dislocation with injury to the brachial artery is described. The rarity of the complication makes the treatment controversial. Conservative treatment should be the first line of management of this vascular complication. PMID- 2271366 TI - A comparison of dilevalol and placebo in the management of isolated systolic hypertension using ambulatory monitoring. AB - 1. The antihypertensive effect of dilevalol, a compound which combines beta adrenoceptor blocking and vasodilating properties due to beta 2-adrenoceptor agonism, was studied in nineteen patients with isolated systolic hypertension (ISH). A randomized, double-blind, placebo-controlled, cross-over trial with two 4 week treatment periods was used to compare the efficacy of once daily dosing with dilevalol (in the range of 100-400 mg daily) against placebo. Assessment of response involved both casual blood pressure readings (amongst all patients) and 24 h ambulatory blood pressure monitoring (in ten of the nineteen patients). 2. A mean fall of 12/5 mm Hg (s.e. mean 3/2, P less than 0.05) and 9/3 mm Hg (s.e. mean 3/2, P less than 0.05) in supine and standing blood pressure respectively was observed with dilevalol. Mean heart rate was unchanged. The ambulatory monitoring profile demonstrated a smaller reduction in mean blood pressure (7/8 mm Hg) over the 24 h period and a reduction of 10/11 mm Hg over the daytime period. A blunting of the early morning increase in systolic pressure was observed with dilevalol. 3. The drug was well tolerated with light headedness and lethargy being reported more commonly than with placebo. Biochemical parameters were unaffected. 4. It is concluded that dilevalol in the doses used has a small but measurable antihypertensive effect as monotherapy in the treatment of ISH. PMID- 2271367 TI - Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind cross-over study. AB - 1. The effect of clomipramine and desipramine on diabetic neuropathy symptoms was examined in a double-blind, randomised, placebo controlled, cross-over study for 2 + 2 + 2 weeks. Drug doses were adjusted according to the sparteine phenotype, i.e. extensive metabolisers were treated with 75 mg clomipramine day-1 and 200 mg desipramine day-1 whereas poor metabolisers were treated with 50 mg day-1 of both drugs. Nineteen patients completed the study. 2. Plasma concentration of clomipramine plus desmethylclomipramine was 70-510 nM in extensive metabolisers, vs 590 and 750 nM in two poor metabolisers. Desipramine levels were 130-910 nM, vs 860 and 880 nM. 3. Both clomipramine and desipramine significantly reduced the symptoms of neuropathy as measured by observer- and self rating in comparison with placebo. Clomipramine tended to be more efficacious than desipramine. Patients with a weak or absent response on clomipramine had lower plasma concentrations (clomipramine plus desmethyl-clomipramine less than 200 nM) than patients with a better response. For desipramine a relationship between plasma concentration and effect was not established. 4. Side effect ratings did not differ for clomipramine and desipramine and on both drugs three patients withdrew due to side effects. 5. Compared with earlier results obtained with imipramine dosed on the basis of plasma level monitoring, clomipramine and desipramine on fixed doses appeared less efficacious whereas the side effect profiles were the same. At least for clomipramine, appropriate dose adjustment on the basis of plasma level monitoring may increase the efficacy. PMID- 2271368 TI - The influence of clinical and pharmacological factors on enuresis treatment with imipramine. AB - 1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels. PMID- 2271369 TI - A double-blind, placebo controlled, cross-over comparison of the analgesic effect of ibuprofen 400 mg and 800 mg on laser-induced pain. AB - 1. The analgesic efficacy of single oral doses (400 mg, 800 mg) of ibuprofen on argon laser-induced pain was studied in a double-blind, placebo controlled, three way cross-over comparison. Ten healthy volunteers participated. 2. Pain thresholds and plasma concentrations of the S- and R-enantiomers of ibuprofen were measured every hour up to 8 h after medication. 3. Ibuprofen (400 mg) produced an analgesic effect significantly superior (P less than 0.05) to placebo 1-4 h after medication. Ibuprofen (800 mg) was significantly superior to placebo 2-4 h after administration. No differences were found between 400 mg and 800 mg, when hourly threshold differences were compared. 4. Comparing total analgesic effect (area under effect curve), both active medications were superior to placebo (P less than 0.01-0.05), and 400 mg was superior to 800 mg (P less than 0.05). 5. Peak plasma concentrations of S- and R-ibuprofen occurred between 1.2 and 1.5 h. Concentrations after the 800 mg dose were higher than those after the 400 mg dose at all times. PMID- 2271370 TI - End-stage renal disease and non-narcotic analgesics: a case-control study. AB - 1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesics taken at least every other day for 30 days or longer before the first symptom of renal disease was 2.89 (95% CI, 1.78 to 4.68). 3. The risk increased in relation to the use duration. 4. The previous regular consumption of combinations containing phenacetin was strongly associated with ESRD (odds ratio, 19.05; 95% CI, 2.31 to 157.4). The odds ratio for previous regular consumption of salicylates was 2.54 (95% CI, 1.24 to 5.20) and for pyrazolones 2.16 (95% CI, 0.87 to 5.32). 5. An analysis for possible confounding by a history of repeated headaches, arthritis, kidney stones, hypertension, and diabetes did not alter the results. 6. The odds ratio estimates for different pathological subgroups of ESRD patients in relation to previous use of any non-narcotic analgesic were glomerulonephritis. 10.57 (95% CI, 1.25 to 89.0), interstitial nephritis, 3.33 (95% CI, 1.21 to 9.17), cystic kidney disease, 0.71 (95% CI, 0.25 to 1.97), and unknown, 5.15 (95% CI, 2.29-11.57). 7. The results of this study suggest that the regular consumption of analgesics should be routinely considered as a risk factor for any non-congenital cause of chronic renal failure. They also suggest that the risk of ESRD associated with the regular consumption of phenacetin is much higher than the risk associated with other non-narcotic analgesics. PMID- 2271371 TI - Fractionated ifosfamide therapy produces a time-dependent increase in ifosfamide metabolism. AB - 1. Fifteen patients received 1.5 g m-2 of ifosfamide intravenously over 0.5 h every day for 5 days. Twenty-one courses of treatment were studied. Plasma was assayed for ifosfamide by gas liquid chromatography and plasma alkylating activity was measured using the nitrobenzylpyridine (NBP) reaction. 2. A pharmacokinetic analysis revealed a significant decrease in the median (range) elimination half-life of ifosfamide from 7.2 (2.8-14.2) h on day 1 to 4.6 (2.3 7.7) h on day 5 (P less than 0.001, Wilcoxon's test) with a concomitant significant increase in the median (range) clearance from 66 (31-148) ml min-1 on day 1 to 115 (52-381) ml min-1 on day 5 (P less than 0.001). There was no significant change in the volume of distribution on day 5 compared with day 1. 3. There was a highly significant 223% increase in the median (range) plasma nitrobenzylpyridine alkylating activity area under the curve on day 1 from 16 (0.6-105) nmol nor nitrogen mustard equivalents ml-1 h to 52 (13-238) nmol nor nitrogen mustard equivalents ml-1 h on day 5. 4. During five courses of treatment (in five patients in the group) 24 h urine samples were collected on days 1 and 5. The median (range) renal clearance of ifosfamide on day 1 was 6.8 (1.3-16.2) ml min-1 compared with 5.7 (1.3-15.3) ml min-1 on day 5. This difference was not significant. The median (range) metabolic clearance of ifosfamide in these five patients on day 1 was 78.6 (39.9-141.2) ml min-1 and 132.6 (54.6-149.5) ml min-1 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271372 TI - The effect of cholestyramine and activated charcoal on glipizide absorption. AB - 1. The interference of cholestyramine and activated charcoal with the absorption of glipizide was studied. 2. In a cross-over study comprising three phases, single doses of cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers together with a single dose of glipizide. 3. The absorption of glipizide was moderately (29%, P less than 0.01) reduced by cholestyramine and greatly reduced (81%, P less than 0.01) by activated charcoal. 4. If cholestyramine and glipizide are used concomitantly, glipizide should be taken 1-2 h beforehand. In acute glipizide overdosage, activated charcoal can be used to reduce absorption. PMID- 2271373 TI - Pharmacokinetics and pharmacodynamics of oxazepam and metabolism of paracetamol in severe hypothyroidism. AB - 1. The effect of severe hypothyroidism on the pharmacokinetics and pharmacodynamics of oxazepam 15 mg given orally (n = 10) and the metabolism of paracetamol 750 mg given intravenously (n = 8) was investigated before and after treatment with levothyroxine. 2. The median total and unbound clearance of oxazepam increased significantly during the study period from 0.78 ml min-1 kg-1 (0.40-1.25) to 1.22 ml min-1 kg-1 (0.66-1.94) and from 9.3 ml min-1 kg-1 (5.2 14.2) to 15.9 ml min-1 kg-1 (7.8-21.8), respectively (P less than 0.01). 3. The elimination half-life of oxazepam was prolonged by hypothyroidism to a median (range) value of 9.3 h (5.4-21.9) compared with 7.5 h (4.8-10.5) in the euthyroid state (P less than 0.05). 4. Hypothyroidism did not affect the protein binding of oxazepam; median values of the free percentage being 8.2% as compared with 7.7% when euthyroid. 5. The median (range) clearance of paracetamol under hypothyroid conditions was 3.12 ml min-1 kg-1 (1.64-4.40) and 4.70 ml min-1 kg-1 (3.18-5.70) following replacement therapy (P less than 0.01). This increase was associated with a comparable increase in the partial clearance to the glucuronide metabolite: 1.86 ml min-1 kg-1 to 2.70 ml min-1 kg-1. 6. Hypothyroidism was associated with decreased performance in a finger tapping test that was exacerbated by oxazepam. When the patients were euthyroid oxazepam did not produce any effect. PMID- 2271374 TI - Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin. AB - 1. The potential interaction between racemic warfarin given as a 25 mg single oral dose and chronically administered ketorolac was studied in 12 young healthy male volunteers. 2. Ketorolac produced no major change in the pharmacokinetics of (R)- or (S)-warfarin. 3. Ketorolac did not alter the pharmacodynamic profile of racemic warfarin. 4. Ketorolac increased template bleeding time by a factor of 1.35 as compared with placebo. 5. The results suggest that the ketorolac-warfarin interaction is unlikely to be of major clinical significance; however, combined use of ketorolac and warfarin in patients should be undertaken with due caution and appropriate monitoring. PMID- 2271375 TI - Propranolol oxidation by human liver microsomes--the use of cumene hydroperoxide to probe isoenzyme specificity and regio- and stereoselectivity. AB - 1. Three oxidations of the enantiomers of propranolol were studied in human liver microsomes under two reaction conditions. Previous in vitro studies had established that two of the livers were from poor metaboliser (PM) phenotypes for the debrisoquine 4-hydroxylase (cytochrome P-450IID6) and the remaining seven were from extensive metaboliser (EM) phenotypes. 2. In the presence of NADPH and oxygen 4- and 5-hydroxylation of propranolol occurred in microsomes from all nine livers, as did propranolol N-desisopropylation. R(+)-propranolol was oxidized preferentially along the three pathways, although enantioselectivity observed for N-desisopropylation may have arisen not only from stereoselectivity in formation rates, but also from stereoselectivity in subsequent microsomal metabolism, possibly by monoamine oxidase. The involvement of monoamine oxidase in the further microsomal metabolism of N-desisopropylpropranolol was indicated by inhibition of the metabolism of this compound when incubated with phenelzine. 3. Cumene hydroperoxide has been proposed to support only the activity of cytochrome P450IID6. This is consistent with the observations that a) propranolol 4- and 5 hydroxylation occurred in microsomes from the EM livers only and b) side-chain oxidation was not observed under these conditions in either PM or EM livers. 4. Using cumene hydroperoxide to support the reactions, the 4-hydroxylation of propranolol showed little enantioselectivity, whereas S(-)-propranolol was 5 hydroxylated about twice as fast as the R(+)-enantiomer. There were highly significant correlations between the rates of 4- and 5-hydroxylation of R(+) propranolol (r = 0.96, P less than 0.001, n = 7 livers) and of S(-)-propranolol (r = 0.98, P less than 0.001). Both oxidations were described by single-site Michaelis-Menten kinetics. 5. The findings suggest that P450IID6 is involved in both the 4- and 5-hydroxylations of propranolol, but that these metabolites can also be formed by other P450 isoenzymes. It is confirmed that P450IID6 does not contribute to the N-desisopropylation of propranolol. Furthermore, the finding that mephenytoin did not inhibit the appearance of this metabolite is not consistent with the results of in vivo studies suggesting the involvement of the same enzyme in the side-chain oxidation of propranolol and the 4-hydroxylation of mephenytoin. PMID- 2271376 TI - The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man. AB - 1. The N-hydroxylation of dapsone is thought to be responsible for the methaemoglobinaemia and haemolysis associated with this drug. We wished to investigate the effect of concurrent administration of cimetidine (400 mg three times per day) on the disposition of a single dose (100 mg) of dapsone in seven healthy volunteers in order to inhibit selectively N-hydroxylation. 2. The AUC of dapsone (31.0 +/- 7.2 micrograms ml-1 h) was significantly increased (P less than 0.001) in the presence of cimetidine (43.3 +/- 8.8 micrograms ml-1 h). 3. Peak methaemoglobin levels observed after dapsone administration (2.5 +/- 0.6%) were significantly (P less than 0.05) reduced in the presence of cimetidine (0.98 +/- 0.35%). 4. The percentage of the dose excreted in urine as the glucuronide of dapsone hydroxylamine was significantly (P less than 0.05) reduced in the presence of cimetidine (34.2 +/- 9.3 vs 23.1 +/- 4.2%). 5. Concurrent cimetidine therapy might reduce some of the haematological side-effects of dapsone. PMID- 2271377 TI - Apomorphine-induced blinking and yawning in healthy volunteers. AB - Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine-dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg-1 s.c.), was compared with a placebo in a double-blind latin-square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose-related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10-30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine-induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man. PMID- 2271378 TI - Absence of magnesium sparing effect of a single dose of triamterene in combination with frusemide in healthy male adults. AB - In a study of cross-over randomized design in 12 healthy volunteers we compared the effect on magnesium excretion after administration of single oral doses of frusemide 40 mg (F) and of frusemide 40 mg in combination with a single dose of triamterene 50 mg (F+T). F as well as F+T induced significant increases in volume, sodium and magnesium mean 24 h output as compared with 24 h renal excretion without medication. Addition of triamterene to frusemide significantly reduced the 24 h potassium excretion, but did not attenuate the excretion of magnesium. The time to reach the maximum magnesium excretion rate after F as well as after F+T administration was similar to that of the sodium excretion rate. We conclude that triamterene does not inhibit the magnesiuric effects of frusemide in healthy male adults. PMID- 2271379 TI - Frequency of impaired mephenytoin 4'-hydroxylation in an Indian population. PMID- 2271380 TI - Dissociation between inositol polyphosphate production and mitogenesis in mouse thymocytes. AB - Cortical and medullary thymocytes can be separated from each other by virtue of the fact that only cortical thymocytes bear peanut agglutinin (PNA) receptors. The mitogenic responses of subpopulations of thymocytes were studied. We have confirmed the results of Conlon et al. [(1982) J. Immun. 128, 797-801], that lectin-induced stimulation of unseparated cells, and PNA- but not PNA+ thymocytes, results in DNA synthesis. In contrast, both subpopulations, as well as unseparated cells, synthesize DNA in response to the calcium ionophore A23187 in the presence of the phorbol ester TPA, suggesting an impairment of signal transduction in PNA+ cells. However, comparable amounts of inositol phosphates were accumulated in PNA- and PNA+ thymocytes in response to Concanavalin A (Con A). We suggest that mitogenic lectins generate a third signal in addition to elevation of intracellular free calcium concentration and activation of protein kinase C. This signal is generated in PNA- but not in PNA+ thymocytes and is obligatory for lectin-induced stimulation. PMID- 2271381 TI - Communicable diseases. Epidemiological situation in 1989. PMID- 2271383 TI - Influenza in the world. 1 October 1989-30 September 1990. PMID- 2271382 TI - Diarrhoeal Diseases Control Programme. Supervisory skills training course. PMID- 2271384 TI - Tuberculosis elimination: update. PMID- 2271385 TI - Mortality among United Kingdom servicemen who served abroad in the 1950s and 1960s. AB - The Registrar General's decennial supplements on occupational mortality provide only limited information on mortality in the armed forces in the United Kingdom. Mortality has therefore been studied among a group of 30,619 United Kingdom servicemen who served abroad in tropical or desert areas in the 1950s and 1960s, and who remained in the services for a total of at least five years. Mortality from all causes of death, all neoplasms, and all other known non-violent causes was lower than that expected from rates for all men in England and Wales, whereas mortality from accidents and violence was raised. These differences remained after adjustment for social class, affected both officers and other ranks, and had not disappeared even after the men had been followed up for at least 20 years. When mortality from 20 specific cancers and 10 other disease groups was examined there were significant excesses for cancers of the oesophagus (standardised mortality ratio (SMR) = 146; p = 0.03) and prostate (SMR = 156; p = 0.03), and significant deficits for cancers of the lung (SMR = 73; p less than 0.001), stomach (SMR = 66; p = 0.002), bladder (SMR = 53; p = 0.02), other specified neoplasms (SMR = 48; p = 0.001), coronary heart disease (SMR = 76; p less than 0.001), bronchitis, emphysema, and chronic obstructive lung disease (SMR = 42; p less than 0.001), and for five further groups of diseases unrelated to smoking or alcohol. Examination of mortality in each of the three services separately identified two specific hazards in the Royal Navy; seven deaths from mesothelioma occurred compared with less than 2.06 expected (p less than 0.005), and there was also an excess of neoplasms and of other diseases associated with alcohol (SMRs of 181 and 229; p = 0.002 and less than 0.001). Mortality from smoking related diseases other than those associated with alcohol was low in all three services, particularly among officers. PMID- 2271386 TI - A cohort study on the mortality of firefighters. AB - This study was set up to investigate the effect of exposure to combustion effluents on the chronic health of firefighters. A cohort of firefighters was followed up through 10 years with regard to cause specific mortality. Comparisons were made with another cohort of civil servants and salaried employees in physically demanding jobs. After a latency of five years, an excess mortality from cancer was seen for persons aged 30 to 74 (standardised mortality ratio (SMR) 173, 95% confidence interval (95% CI) 104-270). A significant increase in lung cancer was seen in the group aged 60 to 74 (SMR 317, 95% CI 117-691), whereas non-pulmonary cancer was significantly increased in the group aged 30 to 49 (SMR 575, 95% CI 187-1341). It is concluded that inhalation of carcinogenic and toxic compounds during firefighting may constitute an occupational cancer risk. An extended use of respiratory protective equipment is advocated. PMID- 2271387 TI - Cancer risk among glass factory workers: an excess of lung cancer? AB - A total of 3749 workers employed for at least three months in two Finnish glass factories (cohorts A and B) were followed up for cancer in 1953-86 through the Finnish Cancer Registry. In cohort A (1353 men, 1261 women), 106 primary cancers were diagnosed among men, and their standardised incidence ratio (SIR) for all cancers was 99. Among women the risk was low (65 cases, SIR 64). In cohort B (450 men, 685 women), the relative risk of cancer was close to unity for both men (57 cases) and women (75 cases). The risk of cancer was analysed by primary site, type of work, years since first exposure, and age at diagnosis. The only significantly increased risks were those of lung cancer among men (SIR 130, 95% CI 100-167, cohorts A and B combined), and skin cancer among glass blowers (SIR 625, 95% CI 129-1827). An increased risk of lung, stomach, and colon cancer as well as of brain tumours has been reported in previous studies. It is postulated that the excess risk of lung cancer, detected in this study, can also be accounted for by lifestyle, and not only by possible occupational exposures, because a similar excess risk of lung cancer has been found previously for all industrial workers in Finland. Although the risk of stomach cancer in this study was increased among glass blowers, it was not high in the largest groups of plain glass workers. The risks of tumours of the central nervous system and colon were not increased either. PMID- 2271388 TI - Visual evoked potentials in rotogravure printers exposed to toluene. AB - Visual evoked potentials (VEPs) from stimulation by checkerboard pattern reversal were examined in 54 rotogravure printers exposed to toluene (all men, aged 22-64 years, duration of exposure 1-41 years). A control group consisted of 46 subjects (23 men and 23 women; aged 22-54 years). Compared with controls the exposed group showed more frequent responses with reduced reproducibility or absence of some waves, or both; the mean P1 wave latency was prolonged and mean amplitudes N1P1 and P1N2 were reduced. The VEPs were abnormal in 24% of workers. The frequency of abnormal VEPs correlated positively with the duration of exposure to toluene and also with the degree of alcohol drinking. No association was found between measurements of VEP and electroencephalogram (EEG) or electromyogram (EMG) examinations. A VEP measurement was made in 78% of the exposed workers two years after the first examination. No statistically significant difference between the two results was found. This suggests a marked stability of the observed VEP changes. These changes can be interpreted as a subclinical sign of dysfunction of the central nervous system (CNS) related to exposure to toluene and also to alcohol consumption. PMID- 2271389 TI - Exposure to hydrogen sulphide and respiratory function. AB - A study was carried out to assess possible effects of low concentrations of hydrogen sulphide on respiratory function. The cohort comprised 26 male pulp mill workers (mean age 40.3, range 22-60 years) with a daily exposure to hydrogen sulphide in the workplace, and 10 volunteers, who had asthma (three men, mean age 40.7, range 33 to 50 years, and seven women, mean age 44.1, range 31 to 61 years). The respiratory function of the pulp mill workers was monitored by measuring forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and bronchial responsiveness after at least one day off work and at the end of a workday. Bronchial responsiveness was tested by challenge with histamine. The 10 asthmatic subjects were exposed in laboratory conditions to 2 ppm of hydrogen sulphide for 30 minutes in an exposure chamber. Airway resistance (Raw) and specific airway conductance (SGaw) were assessed by a body plethysmograph, and the ventilatory capacities were measured with a flow volume spirometer. No significant changes in respiratory function or bronchial responsiveness related to exposure to hydrogen sulphide in the pulp mill workers were found. In the asthmatic subjects, Raw was increased by 26.3% and SGaw was decreased by 8.4% on average after exposure to hydrogen sulphide. These changes were not statistically significant. In two subjects, however, changes were greater than 30% in both Raw and SGaw, indicating bronchial obstruction. It is concluded that exposure for a relatively short time to hydrogen sulphide concentrations appreciably higher than those existing in ambient air do not cause noticeable effects on respiratory function. PMID- 2271390 TI - Pulmonary effects of acute exposure to degradation products of sulphur hexafluoride during electrical cable repair work. AB - Six electrical workers accidentally exposed to degradation products of sulphur hexafluoride (SF6) during electrical repair work were followed up for one year. One degradation product, sulphur tetrafluoride (SF4), was identified from worksite measurements. Unprotected exposure in an underground enclosed space occurred for six hours over a 12 hour period. Initial symptoms included shortness of breath, chest tightness, productive cough, nose and eye irritation, headache, fatigue, nausea, and vomiting. Symptoms subsided when exposure was interrupted during attempts to identify the cause of the problem. Although exposure ended after several hours, four workers remained symptomatic for between one week and one month. Pulmonary radiographic abnormalities included several discrete areas of transitory platelike atelectasis in one worker, and a slight diffuse infiltrate in the left lower lobe of another. One worker showed transient obstructive changes in tests of pulmonary function. Examination at follow up after one year showed no persistent abnormalities. Preliminary data from this paper were presented at the VIIth international pneumoconioses conference. Pittsburgh, PA, August 1988. PMID- 2271391 TI - Hydrocarbon exposure, pancreatitis, and bile acids. AB - The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons. PMID- 2271392 TI - Differences in frequency of finger tremor in otherwise asymptomatic mercury workers. AB - Tremor was measured from the index finger during low force, position holding in 18 control subjects and 18 battery workers with low level exposure to mercury. All workers were asymptomatic on clinical neurological examination. No differences were found in average tremor amplitudes between the groups, but statistically significant abnormalities in tremor frequency distribution existed. Tremor power spectra in the group of mercury workers were shifted toward the higher frequencies and compressed into narrow frequency peaks. These results suggest that measurements of finger tremor that evaluate the frequency distribution can produce a higher diagnostic yield than traditional visual clinical judgement. The findings also confirm other reports that currently permitted exposures to mercury are associated with subtle but distinctive differences in tremor accompanying voluntary movement. PMID- 2271393 TI - Alterations in laryngeal mucosa after exposure to asbestos. PMID- 2271394 TI - Asbestos related abnormalities among United States merchant marine seamen. PMID- 2271395 TI - Asbestos: a chronology of its origins and health effects. PMID- 2271396 TI - Cellular mechanisms in hypertension and therapeutic implications in blacks. PMID- 2271397 TI - Cellular mechanisms in hypertension and therapeutic implications in blacks. AB - The high incidence and prevalence of hypertension in the black community in western societies led to early speculation that the black population consumed more sodium (sodium chloride) than the general population. However, numerous studies have failed to support this conclusion. It seems rather that it is the handling of sodium by the kidney (greater salt sensitivity) by many hypertensive blacks and the interaction of sodium with potassium, probably magnesium, calcium, and various transport systems at the cellular level that offer a better explanation of these observed phenomena. PMID- 2271398 TI - Changes in sodium-lithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah. AB - We have previously reported from a cross-sectional study that plasma total cholesterol, triglycerides, and HDL-C were significantly and independently correlated with Na(+)-Li+ countertransport. These original participants were rescreened 2 1/2 years later (range of 20-58 months), with lipid, blood pressure, and Na(+)-Li+ countertransport measurements from both visits on 906 normotensive adults. The correlation found between age- and sex-adjusted triglyceride levels and Na(+)-Li+ countertransport at visit 1 (r = 0.34, p less than 0.0001) was reconfirmed at visit 2 (r = 0.32, p less than 0.0001). The Na(+)-Li+ countertransport correlations with HDL-C (r = -0.11, p less than 0.01) and body mass index (r = 0.24, p less than 0.0001) also remained at visit 2. After 30 months, there were significant increases of triglyceride, body mass index, blood pressure, and Na(+)-Li+ countertransport levels, and significant decreases of HDL C and total cholesterol levels, after adjusting the changes in these variables between visit 2 and visit 1 for age, sex, time between the two visits, and the visit 1 level of the variable. Increases in triglycerides, cholesterol, and body mass index were significantly correlated with increases in Na(+)-Li+ countertransport (r = 0.23, r = 0.19, and r = 0.21, respectively). The correlations of the lipid and lipoprotein changes with Na(+)-Li+ countertransport changes were independent of body mass index and blood pressure changes. We conclude that increasing plasma triglyceride levels and body mass index are associated with increasing Na(+)-Li+ countertransport levels in both cross sectional and longitudinal data. PMID- 2271399 TI - A study of urinary and intracellular sodium and potassium, renin, aldosterone, and hypertension in blacks and Indians in Natal. AB - The prevalence of hypertension in the urban black population in Sub-Saharan Africa is high and varies from 20% to 25%. In contrast, the prevalence of hypertension in the rural black is relatively low. In Natal the prevalence of hypertension in a large metropolitan city, Durban, is 25% in the adult Zulu, 17.2% in whites, and 14.2% in Indians. The prevalence of hypertension in the rural Zulu of Natal is 10%. Work on the pathogenesis of hypertension in the Zulu and Indian ethnic groups related to renin, aldosterone, dietary sodium and potassium, and intracellular sodium and potassium was virtually nonexistent. This review paper summarizes the salient features that were found. PMID- 2271400 TI - Racial differences in antihypertensive therapy: evidence and implications. AB - Blood pressure is controlled by many factors, and thus hypertension is a multifactorial disorder. This etiologic diversity is also reflected in the broad spectrum of different pharmacologic agents known to lower blood pressure. Most carefully controlled studies employing a single antihypertensive drug in unselected, uncomplicated mild to moderate hypertensives demonstrate efficacy in reducing blood pressure in 40-60% of the population. If two agents of differing pharmacologic actions are combined, success rates of 70-90% are generally observed. Specific choices of antihypertensive agents have heretofore been based on whimsy, hearsay, or empiricism. More recent studies have identified characteristics that may help to predict the efficacy of single drugs. These characteristics have included physiologic factors, such as sodium sensitivity, plasma renin activity, or sympathetic nervous system activity, as well as demographic components, particularly age and race. This review will examine the effects of racial classification on the blood pressure response to antihypertensive agents. PMID- 2271401 TI - Obesity and hypertension in blacks. AB - In the United States, obesity and hypertension are more common in blacks than in whites, but that general statement hides some important sex differences. Thus, in black women the prevalences of both obesity and hypertension are greater than in white women, whereas in men, although there is no racial difference in obesity, in blacks hypertension is more common and more severe than in whites. For white people, there is a well-documented causal relationship between obesity and hypertension, however, results from the second National Health and Nutrition Examination (NHANES II) suggest that this relationship is not so strong for blacks. Obesity is also an important risk factor for diabetes, which in itself is associated with hypertension. The mechanism of obesity-associated hypertension appears to be an inadequate vasodilation in the face of the increased blood volume and cardiac output, which are the natural consequences of an increased body mass. This defect in control of vascular resistance has been attributed to increased activity of the sympathetic nervous system, abnormal renin-angiotensin aldosterone relationships, and insulin resistance. However, none of these attributes has been found to be the exclusive characteristic of obese hypertensive as compared with normotensive obese subjects. PMID- 2271402 TI - Potassium and calcium intake, excretion, and homeostasis in blacks, and their relation to blood pressure. AB - Blacks in the United States have higher blood pressures than whites. They ingest and excrete less calcium and potassium. There is some evidence that blacks have a difference in vitamin D metabolism that might increase any problem caused by low calcium intake. Some studies can be interpreted to suggest that calcium or potassium therapy has greater hypotensive effects in blacks than in whites. Decreased intake of calcium and potassium may be major causes of the greater prevalence of hypertension in blacks than in whites. PMID- 2271403 TI - On the optimality principle in a bio-flow absorption system: an analysis of the Jmax-Kt relationship in the proximal tubule of the kidney. AB - The absorption process of sugars and amino acids in the proximal tubule of the kidney is one of the typical examples of operation of bio-flow absorption systems in the living body. The relationship between two kinetic parameters of the Michaelis-Menten equation, Jmax and Kt, which are the main determinants of the reaction velocity in the absorption process, was investigated by using experimentally obtained data for several actively transported substances and a mathematical model of the proximal tubule. When examined the data of the parameters for sugars and amino acids obtained from both amphibian (Triturus) and mammalian (rat) kidneys, a distinct and common tendency was found such that a high affinity system has a low capacity and vice versa. For all substances tested in this study, the calculated concentration profile along the tubule monotonically reduced to zero at around the middle portion of the tubule, although each substance has considerably different values of Jmax and Kt. From the digital simulation, the observed Jmax-Kt relationship among the tested substances could be explained in terms of the optimality principle, by which all the systems could accomplish absorption with a sufficient reserve capacity within a limited length of the tubule. The importance of such an elaborated arrangement of the transport systems in the renal proximal tubule is discussed from the viewpoints of evolution and functional speciality of the organ. PMID- 2271404 TI - Cardiac mechanics and energetics--from Emax to PVA. AB - After these seven decades of cardiac mechanics, through the windows of Starling's cardiac output curve followed by Sonnenblick's myocardial force-velocity relation and Vmax, Frank's ventricular pressure-volume (P-V) relationship has revived as a window of cardiac mechanics over the past two decades following the proposal of the Emax concept by Suga and Sagawa. Emax is a physically sound measure of ventricular contractile compressibility or time-varying volume elastance at end systole. Although the original Emax concept has been slightly modified to improve its fitness to reality, the Emax concept has successfully survived over two decades as a basic conceptual framework of ventricular contraction in physiological, pathophysiological and clinical studies. An important expansion of the Emax concept was introduced by Suga a decade ago, and a new window for cardiac energetics was opened up by the concept of PVA as a measure of the total contractile energy generated by ventricular contraction. PVA correlates with ventricular oxygen consumption, with Emax as a decisive parameter. Moreover, Emax and PVA combined with effective arterial elastance Ea as a new afterload parameter proposed by Sunagawa and Sagawa have enabled us to predict cardiac energetics under a variety of loading and contractile conditions. The key advances of the Emax and PVA concepts are reviewed mainly in the biomedical engineering aspects by the proposer of these concepts himself. PMID- 2271405 TI - Recording vectorcardiographic loops with a microdot thermal printer. AB - The principle of recording vectorcardiographic loops with a microdot thermal printer is developed using a very small memory area. It is based on two previous achievements: (i) orthogonal electocardiogram derivation from the conventional 12 lead system and (ii) recoding of biomedical signals with a microdot thermal printer, thus permitting the VCG to be just an extension of the standard ECG. The principle consists of decomposing the loop into horizontal sectors each one representing a non-ambigous function. It is implemented in ECG instruments, using the Gotemba microdot thermal printers TLP 480Z and TLP 880Z produced in Japan. PMID- 2271406 TI - Compound action potential amplitude and conduction velocity as a function of temperature in carp nervus lateralis. AB - This study shows the relationship between nerve fiber conduction velocity of compound action potentials produced by bipolar electrical stimulation were recorded from the isolated carp nervus lateralis by means of an electrode array consisting of 16 0.5 mm diameter platinum wire electrodes mounted in a nerve chamber. The recordings were repeated at temperatures ranging from 12.0 to 32.5 degrees C. Both the amplitude and conduction velocity of the nerve response peaked at about 28.0 degrees C. First-order mathematical approximations of conduction velocity and response waveform as a function of temperature were developed based on these data. The nerve response depending on temperature is distinguished by microscopic photography. PMID- 2271407 TI - A method for the elimination of artefacts in electric field plethysmography of the lung. AB - The reliability of electric plethysmography for respiration monitoring is reduced by artefacts caused by the cardiac activity, by motions, electromagnetic cross talk and others. For artefact suppression, a constant-current field plethysmography technique is discussed which uses the voltage of an auxiliary electrode in addition to the conventional four-electrode arrangement. By means of a differential amplifier, a respiration signal is produced which is almost entirely free from heart artefacts, while the intensity of additional artefacts is suppressed. In principle, the technique can also be used for the separate determination of the ventilation intensity of the two lungs. PMID- 2271408 TI - Definition of axial rotation of anatomical joints. PMID- 2271409 TI - Breast cancer screening by impedance measurements. AB - More efficient screening for breast cancer can lead to a reduction in the need for radical surgery and improved survival rates. Modern technology, particularly electronics and computerized instrumentation, makes such improvement feasible. We have developed an instrument for screening for breast cancer based on measuring the dielectric properties of tissues. An image of the electric properties of the breast is presented on a monitoring screen, using 512 'pixels', from which it is possible to distinguish pathological tissue. The image can be recalled on the monitor at will. The test can be performed by paramedical personnel. In the present study 6000 patients were tested with this instrument; 745 of these have undergone biopsy and these had been tested with all available instrumentation. A number of cases were found in which only this instrument detected a pathology which proved malignant. Instruments of such a type could become an additional part of breast cancer clinics. PMID- 2271410 TI - Prediction of central apnea episodes in infants during sleep. AB - This study describes a prediction method for central apnea episodes of newborns during sleep. The cross-correlation between heart rate and respiration obtained from newborns is calculated. Employing the cross-correlation, the displacement between heart rate and respiration before central sleep apnea episodes was much larger than the displacement in the stationary state. As the result, it is possible to predict central sleep apnea episodes several minutes before their occurrence. PMID- 2271411 TI - Catheter-type defibrillation electrode using glassy carbon: results of electrode implantation. AB - The implantable defibrillator, developed by Dr Michel Mirowski, is a remarkable electric therapeutic device which has been in clinical use since 1980 in the treatment of life-threatening arrhythmia. However, as the present life span of this device is only 3 years, research is being carried on to extend the lifetime with improved stimulation methods, circuits and electrodes. In particular, the electrode system which is inserted into the right ventricle has more than 50 times the electrode area of a pacing electrode and is prone to degradation. What is needed is biocompatibility and electrical stability, similar to that of cardiac pacemaker electrodes, which can be used for more than 10 years. For this purpose, we focused on a conductive ceramic as a new material for the defibrillation electrode instead of the previously-used metal. We selected glassy carbon as our electrode material and tested the surface condition through acute and chronic animal experiments. No clots formed around the electrodes after a 3 month implantation, nor were there surface disorders after the defibrillation stimulations. We concluded that glassy carbon is a promising material for future defibrillation electrodes. PMID- 2271412 TI - Improvement of the frequency responses in an ambulatory ECG system by the natural observation method. AB - The ambulatory ECG system has been used not only in detecting arrhythmia but also in the diagnosis of myocardial ischemia. Therefore, it is necessary to reproduce ECG waveforms as accurately as possible. However, ambulatory ECG waveforms which are in clinical use are apt to be distorted because the frequency responses do not satisfy the AHA (American Heart Association) recommendation which is well accepted as the standard of the conventional ECG system. An improvement of frequency response is reported here using a compensation circuit, whose theory is based on the natural observation method. Since our system is adjusted with square waveforms and composed of a simple analog circuit, it can be compensated easily in real time. In this paper, our newly developed system and various improved ECG signals are presented and compared with conventional ECG signals. As a result, we could obtain less distorted waveforms than from commercially available devices. This new approach enables us to obtain diagnostic information of the distortion free ST segment in ECG waveforms. PMID- 2271413 TI - Hemidiaphragm electro-ventilation in man. PMID- 2271414 TI - Recent technical progress in obstetrics and gynecology in Japan. PMID- 2271415 TI - Two methods for medical image compression. AB - Depending on the purpose for which a medical image is taken, some areas of it contain more clinical information than others. These areas are usually considered as regions of interest (ROI). The area outside the ROI is either the background or contains some clinical information with relative importance. In this paper we introduce two preprocessing and error-free compression routines. The first preprocessing routine, if applied to X-ray images, could result in a reconstructed image with a controllable amount of deterioration in its various areas. The second preprocessing routine is applied to X-ray CT, MR and radionuclide images prior to the compression. Its aim is to automatically detect the ROI and neglect the background. The background is replaced by an optional gray level when these images are being reconstructed. These routines were applied to a variety of medical images and relatively good compression ratios were obtained. PMID- 2271416 TI - In vivo T1 measurements of canine brain for deep tissue temperature measurements with MRI. AB - The possibility of deep tissue temperature imaging with a magnetic resonance (MR) imager was studied in 30 mongrel dogs. The coronary view of the brain of a dog anesthetized with muscle relaxant and pentobarbital and ventilated automatically with air was taken with a special head coil by a 0.1 Tesla MR imager, Asahi Mark J, driven by a spin warp pulse sequence. T1s in the imaging of the right and left white matter, grey matter, thalamus and caudate nucleus were measured with rectal temperature in group I (10 dogs) for a control study every 30 min until 120 min without intervention, in group II (10 dogs) for hyperthermia with extracorporeal bypass method, before heating, at 41 and 42 degrees C, in group III (10 dogs) for hypothermia, before cooling, at 35 and 30 degrees C and after rewarming, respectively. In groups I, II and III, the T1s at all sites except the white matter at 42 degrees C did not change significantly at any rectal temperature. T1 prolongation in the white matter at 42 degrees C may be due to edema, probably because of biological reaction to hyperthermia. The present study suggests that deep tissue temperature imaging in vivo by T1s measured with the MR imager may be impossible in spite of obvious evidence of T1 dependance on temperature in theoretical, in vitro and ex vivo studies already achieved. PMID- 2271417 TI - The pattern of presentation of foot lesions in Nigerian diabetic patients. AB - Foot lesions constitute an important cause of morbidity and mortality in Nigerian diabetics, yet remain poorly characterised. We, therefore, prospectively studied 50 diabetics with 84 major foot lesions over a three-year period at Ibadan, Nigeria. Sixty eight percent of the patients were illiterate and 80% ignorant regarding the importance of footcare. Duration of diabetes was significantly longer in these patients (p less than 0.05) than in age- and sex-matched diabetics without foot lesions. The prevalence rates of neuropathy (68%), foot ischaemia (54%), hypertension (42%) and nephropathy (20%) in diabetics with foot lesions were higher than in previous reported groups of Nigerian diabetics. The initiating factors were predominantly trivial trauma and "spontaneous" blisters. Sixty percent were anaemic at presentation, while short-term glycaemic control was generally poor. Mixed bacterial organisms were cultured in 70% of the cases, with anaerobes presumed present in 33%. Chronic osteomyelitis (38%) and soft tissue changes (35%) were the commonest foot x-ray findings. Some aspects of prevention of foot lesions were discussed. PMID- 2271418 TI - Ultrasonic foetal head circumference as a means of assessing gestational age in Nigerians. AB - In a cross-sectional study, we have established the foetal head circumference in pregnant Nigerian women between the 16th to the 40th weeks of gestation. The relationship between the head circumference and gestational age is linear although there is some slight slowing of the growth rate after 32 weeks. A linear mathematical model was shown to describe the relationship between gestational age and head circumference and with the knowledge of one the other could be determined. The values obtained in this study compared favourably with similar studies amongst caucasians and the value of this data with reference to management of intrauterine growth retardation (IUGR) and foetal weight determinations was discussed. PMID- 2271419 TI - The pattern of somatization symptoms at the Ibadan Teaching Hospital Psychiatric Clinic. AB - A six-month cross-sectional study of consecutive new referrals at the psychiatric clinic of a large general hospital was carried out, aimed at highlighting the pattern of somatization symptoms. Two hundred and six new patients attended the clinic in the period of study. Of this number, 74 (35.9%) presented predominantly with these symptoms. Significantly more males than females had these symptoms. Vague, poorly localised aches and pains were the commonest symptoms complained of by the somatizers. Most of them had each at least three of these symptoms and the symptoms had been commonly present for at least six months before presentation in hospital. Comparatively, few of those with predominant somatic symptoms also spontaneously reported vegetative and psychological symptoms of psychic distress, especially insomnia, palpitations and free-floating anxiety. Although somatization symptoms cut across socio-demographic and clinical diagnostic categories and were experienced in all parts of the body, these symptoms were much commoner among those aged 21 to 40 years, of lower socio-economic status and with a diagnosis of neurosis. Anxiety and depressive neurosis most commonly presented with widespread somatic symptoms. These findings are compared with the results of previous studies and the implications were discussed. PMID- 2271420 TI - Evidence that circulating lymphocytes act as vehicles or viraemia in measles. AB - Previously described giant multinucleated cells were observed in phytohaemagglutinin (PHA) cultures of leucocytes from blood samples of 17 (36%) out of 47 children with measles or undiagnosed fever in Ibadan. The giant cells were more readily seen in PHA cultures of purified lymphocyte preparations than in total leucocyte suspensions. It was concluded that the observation indicates in vivo infection of some blood lymphocytes of patients with measles and related infections by syncitium producing virus to manifest the giant cells seen in culture. The practical application of lymphocyte cultures to the laboratory diagnosis of measles is stressed and the concept of circulating lymphocytes contributing to the systemic spread of measles infection is highlighted. PMID- 2271421 TI - An assessment of national needs for community physician manpower in Nigeria: staff training needs and programmes. AB - This second part of a national survey was designed to identify the training needs and programmes considered most appropriate by the most senior health management staff of the state governments for the field practice of community medicine in Nigeria. The operation of the current primary health care programme and the field practice of community medicine although constitutionally a local government responsibility, effectively rests on the state governments at present because of economic and political constraints at the LG level. The main needs identified in the study are for a certifiable and appropriate generalist community physician training programme as well as the relative levels of emphasis needed in the different sub-specialty areas. While holders of the current fellowship diploma in public health of the National Postgraduate Medical College of Nigeria are welcome to practice in the field if they are available, many state governments and officials consider the programme ill-suited to the needs of field practice community physicians. Thirteen (68.4% of the) respondents, consider it suitable only for jobs at state employment levels and higher up. Twelve of the 17 physician respondents considered clinical practice essential for all community physicians. Eighteen of the 21 state governments would be ready to sponsor their physician candidates to local training programmes in public health as identified in this study, if different from the current postgraduate fellowship. Maternal and child health was the area of sub-specialty training considered most needed in the states. This was followed by epidemiology, environmental health, health education, health and biostatistics, health management, and occupational health in that order.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271422 TI - Factors in the aetiology of hepatic encephalopathy in the tropics. AB - The factors in the aetiology of Hepatic Encephalopathy in the tropics were analysed from the medical and necropsy records of 103 patients. Internal bleeding and infections were the commonest precipitating factors. PMID- 2271423 TI - Mastalgia and breast tumour in Nigerian women. AB - 376 Nigerian women who presented with histologically proved breast tumour (256 benign and 120 malignant) were admitted to a study of mastalgia and breast tumour. A total of 67 patients, consisting of 57 (22.3%) of 256 benign disease patients and 10 (8.3%) of 120 malignant disease patient had pain, compared to 199 (77.7%) benign and 110 (91.7%) malignant disease patients who had no pain. Mastalgia was more often associated with benign tumour (57 out of 67 or 85%) than malignant neoplasm (15%). Adenosis was the leading cause of mastalgia (15 of 26 patients). Surgical extirpation of breast tumour achieved total pain relief in 85% of the patients, but adenosis patients were least likely to achieve total pain relief. PMID- 2271424 TI - Pattern of surgical acute abdomen in the University of Port Harcourt Teaching Hospital. AB - This paper presents a retrospective study on 279 cases of surgical acute abdomen seen and treated at the University of Port Harcourt Teaching Hospital over a period of about 2 1/2 years, September 1983-February 1986. The majority of the patients were in the second and third decades of life. Acute appendicitis and obstructed hernias were the commonest causes of surgical acute abdomen, while abdominal pain and vomiting were the commonest symptoms. Only two patients in the series had acute pancreatitis. The overall mortality was 13.3%. PMID- 2271425 TI - A case-study of accidents in a wood processing industry in Nigeria. AB - A twelve-month case-study of industrial accidents in a large-scale modern wood processing industry in Nigeria shows that 80.6% of the accidents were minor while the rest were major accidents. Incidence rate of the accidents was 64.6/100 workers at risk per year. The accidents appeared to be evenly distributed in the various production sections of the industry except for few but severe cases of head injuries that occurred mainly among the forestry, plywood and sawmill workers. About 39.8% of the accidents were caused by handling objects and 19.4% by falling objects. The incidence rates of the accidents decreased with increasing age and length of experience of the workers. The proportion of sickness absentees due to the accidents was 37.8% with 0.47 mean number of spells and 3.1 mean number of days lost per worker per year. PMID- 2271426 TI - Mortality in eclampsia in the Lagos University Teaching Hospital (LUTH); comparison of the recent 10-year period (1977-1986) with the previous 10 year period (1967-1976). AB - Over a 10-year period, between 1st January 1977 and 31st December 1986, a total of 572 eclamptic patients were treated in the Lagos University Teaching Hospital (LUTH). Three hundred and eighty-four of these patients (66.4%) were pre-delivery eclamptics, while 188 (33.6%) were post-partum eclamptics. The great majority of these cases (448) (98.3%) were unbooked patients. The overall maternal deaths from eclampsia or its complications during the period were 62 (108 per 1000) while the known perinatal deaths associated with the condition was 100 (240 per 1000). The mean Caesarean Section (C/S) rate in the pre-delivery eclamptics was 30.22 +/- SD 19.62%, while the mean C/S rate in all eclamptic patients treated in LUTH during this period was 22.20 +/- SD 15.04%. Comparison of the data from the recent decade to that of the previous decade (1966-1976), shows that the number of eclamptic patients treated in the LUTH, over the recent decade (1977-1986) more than doubled the number of eclamptics treated in the previous decade (1967 1976) (572 as compared with 273 for the previous decade). The overall maternal mortality rate remained unchanged (106 to 108 per 1000), while the perinatal mortality rate increased from 117 per 1000 to 240 per 1000 in the recent decade respectively. The C/S rate in the pre-delivery eclamptics increased during the period from 21.3% in the previous decade to 30.2% in the recent decade. The unbooked eclamptic patients remain the dominant group in the two studies. PMID- 2271427 TI - Oesophageal atresia and tracheo-oesophageal fistula: review of a 10-year personal experience. AB - Eleven neonates with oesophageal atresia and distal fistula were managed between July 1977 and January 1987. The male:female ratio was 1.2:1. The patients were aged between 1 to 14 days (median 7 days) and weighed 1.85 to 3.10 kg (mean 2.6 kg) at presentation. Associated anomalies were present in 5, pneumonia in 4 and uraemia (mean serum urea of 88 mg%) in all patients. A primary repair and simultaneous gastrostomy (omitted in 1) was done for all cases. There were 5 operative deaths. Fifteen postoperative complications occurred in 10 patients; including septicaemia in 3, wound infection in 3, anastomotic leak in 1 and tracheal mucus plug in 1. Statistical analysis indicated no difference between survivors and nonsurvivors on the basis of age, weight, degree of uraemia or presence of pneumonia. One of the 6 survivors (now 5 years after surgery) required bouginage after 26 months and has remained asymptomatic; the other 5 are well and without symptoms 3 to 11 months postoperative. The most significant determinants of survival are the effectiveness of pre- and postoperative managements of patients. PMID- 2271428 TI - A Doppler ultrasound study of vessel compliance changes in occlusive arterial diseases. AB - This study was undertaken to investigate the extent to which the major arteries, particularly the aorta, iliac and leg arteries are involved in certain peripheral occlusive vascular disease, e.g. diabetes mellitus and sickle-cell anaemia. By using a non-invasive Doppler technique, vessel compliance (C) was measured in the aorta, iliac and leg arterial segments of 25 juvenile and adult-onset diabetics of recent diagnosis and also in seven sickle-cell subjects (sicklers) whose conditions were known to have reached crisis state. Results have been compared with values obtained from normal subjects of the same ethnic origin and age group. Abnormal aortic compliances was found in the juvenile diabetics in marked contrast with the lower than normal aortic compliance found in the adult diabetics of over 40 years of age, but also of recent diagnosis. The results further showed that some of the young sicklers (under 30 years of age) have slightly higher blood vessel compliance than normal while the older ones have lower values. These differences in compliance are discussed in the light of previous findings in animal and man. PMID- 2271429 TI - Psychiatric morbidity in a Nigerian general out-patient clinic. AB - In a cross-sectional study of a systematic random sample of new patients attending the clinic of the G.O.P.D. of the University College Hospital, Ibadan, using the PSE, the CES-D and clinical evaluation, at least 40% of 104 subjects were found to have sufficient symptoms of psychic distress to warrant treatment. There was statistically significant association between the measures for psychiatric caseness. Among those rated as psychiatric cases on clinical evaluation, neurosis was the predominant diagnosis. Symptoms of depression were commonly admitted to by these subjects. At review of case notes one year later, the initial diagnoses for those referred to the psychiatric clinic were sustained. In view of the commoness of psychiatric symptoms in general practice, it is suggested that undergraduate psychiatric posting duration be increased; residency training in general practice and internal medicine should include a period of posting in psychiatry; and national health care planning should pay a greater attention to mental health care than is at present the case. PMID- 2271430 TI - Ventilatory function of workers at Okpella cement factory in Nigeria. AB - Simple ventilatory function tests were done in 447 cement factory workers. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were higher in males than females and correlated well with age and height. FEV1 was smaller in workers who were in closer contact with cement dust. The three measured indices of ventilatory function decreased with years of service and the fall was neither accounted for by age nor height. Eleven chronic bronchitics were found, but these were heavy smokers. Overall, the lung volumes obtained were within the normal range for Nigerians. However, the nature of job done in the cement factory, and duration of service may well be important in the aetiology of "cement factory lung disease". PMID- 2271431 TI - The pathological basis of endstage renal disease in Nigerians: experience from Benin City. AB - A prospective study involving 1,980 patients aimed at defining the pathological basis of endstage (chronic) renal failure in Nigerians was carried out over a six year period in Benin City, Nigeria. Using information derived from intravenous pyelography, ultrasonography, renal biopsies and autopsies, it was found that 43% of cases of chronic renal failure were due to hypertensive nephrosclerosis, 33% due to obstructive uropathy and 18% due to chronic glomerulonephritis. Chronic atrophic pyelonephritis was a rare finding. The frequency and severity of essential hypertension in Nigerians and their propensity to go into renal failure are similar to what obtains in American blacks. In a society which cannot afford regular dialysis and transplant facilities, there is need for early detection and adequate treatment of essential hypertension. PMID- 2271432 TI - Plasma levels of chloroquine in healthy Nigerian children: clinical and toxicological implications. AB - 1. Sixteen healthy children attending the Well Baby Clinic of the University of Nigeria Teaching Hospital, Enugu were studied. 2. Upon obtaining a medication history that was negative for chloroquine over a three week period, a single random sample of venous blood was taken from each child for chloroquine analysis. 3. Analysis of plasma for chloroquine was done using an h.p.l.c. method. 4. Plasma levels of chloroquine in the children ranged from 77.8-224.7 ng/ml with a mean of 156.5 +/- 67.8 s.d. 5. In view of the danger of acute toxicity as well as the long-term effects, further studies are needed to determine the harmful effects such perennial presence of chloroquine, albeit in low levels, may have on our children. PMID- 2271433 TI - Safety and efficacy of yellow fever vaccine in children less thanone-year-old. AB - In a clinical trial of stabilized yellow fever vaccine from Institute Pasteur in 77 children aged seven to eight months, fever was the most significant immediate and delayed side effect. Fever occurred in 12 (15.6%) children with in 48 hours of vaccination while it occurred in 10 (12.9%) children within ten days of vaccination. Other recorded side effects were pain at innoculation site in four (5.2%) children and vomiting in one (1.3%) child. Temperature recorded in 20 of the 22 febrile episodes ranged from 37.8 degrees C to 38.6 degrees C. One of the two patients who had temperatures of 39 degrees C and above had malaria parasites in her blood film. All episodes of fever except one responded to antipyretic. There was no episode of febrile convulsion and no feature suggestive of encephalitis. Of the 20 children who had neutralization test carried out against yellow fever virus six weeks after vaccination, the test was positive in post vaccination sera of 12 (60%) children whose pre-vaccination sera were negative. Two others showed evidence of partial protection. Although the seroconversion rate of 60% is less than reported in adults and older children, the result of this study shows that yellow fever vaccine is safe and fairly effective in infants. It is our suggestion that if a larger trial confirms our findings, the vaccine may be incorporated into the expanded programme on immunization (EPI) to be given at the age of seven months after completion of diptheria, tetanus, pertussis and poliomyelitis vaccinations and before measles vaccination is due. PMID- 2271434 TI - Menarche in Plateau State of Nigeria. AB - A study of the age of menarche was conducted in Plateau State of Nigeria during May and June 1984 on a cross-section of the population, which included 664 girls from two schools between the ages of 10 and 21 years using the status quo method. The mean age at which menarche occurred was estimated as well as the standard deviation. The results indicated a mean age of 13.5 years +/- 1.33 (S.D.) for the total population; 13.2 +/- 1.12 (S.D.) for the school in the state capital and 14.0 +/- 1.40 (S.D.) for the school in the rural area. There was a statistically significant difference between the age of menarche of girls in the three different social groups and a secular trend was discovered when menarchal age in this study was compared with a previous study in the same area of Nigeria. The mean menarchal age for Plateau State girls is comparable to other Nigerian studies but higher than current data on European and American girls. PMID- 2271435 TI - Progesterone receptors in advanced breast cancer. AB - Progesterone receptor (PR) assay was performed on tumor specimen obtained from 145 women consisting of 82 women with advanced breast cancer and 73 women with early breast cancer (EBC). Advanced breast cancer patients consisted of 50 (61%) of 82 women with advanced primary breast cancer (APBC) and 32 (39%) women with recurrent or secondary breast cancer (SBC). Of 82 advanced breast cancer, 35 (42.7%) were PR+. These consisted of 21 APBC and 14 SBC patients. 43 (59%) of 73 EBC patients had PR+ tumors. Quantitative value of PR correlated with age in overall and in all groups. There was also a significant difference in PR quantitative value between PR+ tumors and PR- tumors. Finally premenopausal APBC patients with PR+ tumors had a 2:1 survival advantage over those with PR- tumors. PR assay is as an invaluable a tool as ER assay in the management of breast cancer. PMID- 2271436 TI - A study of different doses of atracurium to prevent suxamethonium-induced fasciculations. AB - Pretreatment with 3 different doses of atracurium (0.035 mg/kg, 0.05 mg/kg, 0.07 mg/kg) was investigated in order to determine the optimal dose that would prevent suxamethonium-induced fasciculations with minimal side effects to the patient and without significant antagonism of suxamethonium block. A total of 80 patients was studied. There were 20 patients in each of three atracurium groups while a fourth group of 20 patients served as control. Atracurium reduced the incidence of fasciculations from 100% observed in the control to between 0 and 40% in the atracurium groups. The optimal dose of atracurium appears to be 0.05 mg/kg, using a pretreatment interval of 3 minutes. Routine pretreatment of all patients is not mandatory, but it is recommended whenever the side-effects of suxamethonium are particularly undesirable, as in ocular laceration, raised intracranial pressure, full stomach and in very muscular patients. PMID- 2271437 TI - A biochemical description of nutritional state of a rural population in Nigeria. AB - The nutrient intake and blood chemistry of the people of Kainji Lake Area are presented. The study was conducted to describe the nutritional state of Kainji population. The study shows that the nutrient intake of children below 5 years of age were generally low and this probably accounted for the mild-moderate malnutrition earlier reported upon in this age group. The blood chemistry was shown to be comparable with the national standard for protein and albumin but the mean corpuscular haemoglobin concentration percent revealed iron-deficiency anaemia. Health education of the mothers was suggested as a solution of improvement of child nutrition, and control of environmental sanitation was suggested as a solution to iron-deficiency state in the general population. PMID- 2271438 TI - Age and anthropometric status of Nigerian girls at puberty: implication for the introduction of sex education into secondary schools. AB - Age, height and weight at various stages of pubertal development were assessed in a cross-sectional survey of 1054 schoolgirls living in Ilorin, Nigeria. The first sign of puberty; breast bud and pubic hair development appeared at mean age (year) 12.7 +/- 1.0 and 12.8 +/- 0.9 respectively, and reached full maturational stage at mean age (year) 14.7 +/- 1.3 and 14.4 +/- 1.4 respectively. The mean age, height and weight at which the intermediate stages are reached were given. Cumulative proportion of girls that have attained menarche at each pubertal stage were derived. Median age of menarche calculated by status quo method was 13.6 years. In general, about 50% of girls in each stage of pubic hair development were at corresponding stage of breast development. Only about 75% of girls have full axillary hair growth at Tanner stage--5 of breast and pubic hair development, Longitudinal data to assess growth spurt and peak height velocity are suggested. Introduction of sex education into secondary school classes represented by the pubertal age group is advocated. PMID- 2271439 TI - Acromegaly in Ibadan--a report of six cases. AB - Six patients with acromegaly were seen over a six year period at the University College Hospital, Ibadan, Nigeria. There were 5 males and 1 female giving a sex ratio which differed from the equal sex prevalence observed in larger caucasian series. The diagnosis was made strictly on clinical grounds with corroborative evidence from x-ray of the skull and limbs. An unusual and unexpected finding was the observation of a hernia or a history of herniorrhaphy in 4 out of the 5 male acromegalics. It was not certain whether the association was real or what the explanation might be. Transfrontal surgery was the only definitive form of treatment that could be offered to the patients because of lack of facilities for transphenoidal adenomectomy or pituitary irradiation. The operation was refused by 4 of the 5 patients to whom surgery was recommended because of cultural fears regarding operations on the brain. Bromocryptine was prescribed as an alternative therapy but its scarcity and prohibitive cost precluded any serious compliance. There is a need to highlight the problems of the silent sufferer of endocrine disorders in developing countries. PMID- 2271440 TI - Lawrence-Moon-Bardet-Biedl syndrome: a case report. AB - A case report of the rare Lawrence-Moon-Bardet-Biedl Syndrome in a 10-year old Nigerian boy is presented. The findings were obesity, mental retardation, polydactyly hypogonadism, macula degeneration and retinities pigmentosa. PMID- 2271441 TI - Internal optical urethrotomy: a report of fifty-one cases treated under local anaesthesia. AB - Over the 15-month period beginning from October 1985, internal optical urethrotomy was successfully performed under local anaesthesia on 51 patients with urethral stricture. The procedure was well tolerated and 48 patients were discharged home on the day of operation. A urethral catheter (18 or 20F Foley) was left indwelling for one week post-operatively. Subsequently patency was assessed by check catheterisation using size 18F Nelaton Catheter, weekly for 6 weeks, and then at 3 monthly intervals. Thirty-nine patients have been followed up regularly for 3 to 15 months. Six patients restrictured (failed check catheterisation). The remaining 33 (84.6%) have retained urethral patency with no additional treatment. PMID- 2271442 TI - Spatial- and temporal-frequency selectivity as a basis for velocity preference in cat striate cortex neurons. AB - Measurements were made of the optimal velocity for drifting bar-shaped stimuli to excite striate cortex neurons of the cat. These data were compared to the optimal spatial and temporal frequencies of the same neurons, as determined with drifting sine-wave grating stimuli. A systematic relationship was revealed, whereby those neurons preferring higher velocities of bar motion also preferred lower spatial and higher temporal frequencies of gratings. The optimal bar velocity for a given neuron could be quantitatively predicted from the ratio of that neuron's optimal temporal frequency to its optimal spatial frequency. PMID- 2271443 TI - X- and Y-mediated synaptic potentials in neurons of areas 17 and 18 of cat visual cortex. AB - When a cuff-shaped electrode is placed on the optic nerve of the cat, X and Y axons, by virtue of their different diameters, exhibit different thresholds to electrical stimulation. Large-diameter Y axons have low thresholds, while smaller diameter X axons have high thresholds. There is very little overlap between the two populations. Given this segregation, the strength of stimulation of the optic nerve required to evoke synaptic potentials in cortical neurons becomes a reliable indicator of the type of visual input a cortical neuron receives. Potentials with thresholds below the thresholds of X axons must be mediated by Y cells of the retina and LGN. Potentials with thresholds above the Y axons of the optic nerve must be mediated by X cells. From previous experiments, one would expect to find ample input via both types of axon to area 17 of the visual cortex. This was not the case. Of 58 neurons distributed throughout the layers of area 17 from which intracellular records were taken, in only four could substantial Y excitation be detected. Three of these four were located near the border with area 18. All four received large X inputs as well. The 24 neurons studied in area 18 all received large Y inputs but no detectable X input. PMID- 2271444 TI - X- and Y-mediated current sources in areas 17 and 18 of cat visual cortex. AB - X- and Y-mediated input to areas 17 and 18 of the cat visual cortex was studied using current-source-density analysis of field potentials evoked by stimulation of the optic nerves. A cuff-shaped electrode was used for stimulation so that Y axons, by virtue of their larger diameters, would have lower electrical thresholds than X axons. The effect in each cortical area of activating Y axons alone could therefore be determined by low-amplitude stimulation of the optic nerves. Current-source densities were calculated by two separate methods. (1) In five experiments, field potentials were measured sequentially at different cortical depths with a single tungsten electrode. Current densities were then calculated by computer. (2) In two experiments, current densities were derived in real time from field potentials recorded simultaneously from three sites with a multi-electrode probe. The calculation was performed by an analog circuit specially designed for this purpose. This method has several advantages over the standard, single-electrode method. At stimulus strengths sufficient to activate the majority of Y axons in the optic nerves, but subthreshold to most X axons, the field potentials evoked in area 17 changed little from layer to layer. When the current-source-density analysis was applied to these potentials, no significant sources or sinks were detectable. Only when the stimulus strength was raised to the point that both X and Y axons were activated by the stimulus were any current sources or sinks detected in area 17. The currents were similar in time course and laminar pattern to those recorded after stimulation of the optic chiasm. In area 18, large sources and sinks were evoked by stimulation of Y axons alone. These currents changed little when the stimulus strength was increased to activate X axons as well. Area 18, therefore, in contrast to area 17, seems to be dominated by Y input and receives little X input. These results support the conclusions of the accompanying paper in which synaptic potentials were recorded intracellularly from cortical neutrons. The intracellular experiments failed to show substantial Y input to area 17. The projections of X and Y axons may therefore be much more highly segregated into areas 17 and 18 than previously thought. Alternatively, the nature of the Y input to area 17 may be very different from that to area 18 in that it cannot be easily detected with intracellular or current-source-density techniques. PMID- 2271445 TI - Gain, noise, and contrast sensitivity of linear visual neurons. AB - Contrast sensitivity is a measure of the ability of an observer to detect contrast signals of particular spatial and temporal frequencies. A formal definition of contrast sensitivity that can be applied to individual linear visual neurons is derived. A neuron is modeled by a contrast transfer function and its modulus, contrast gain, and by a noise power spectrum. The distributions of neural responses to signal and blank presentations are derived, and from these, a definition of contrast sensitivity is obtained. This formal definition may be used to relate the sensitivities of various populations of neurons, and to relate the sensitivities of neurons to that of the behaving animal. PMID- 2271446 TI - Developing eyes that lack accommodation grow to compensate for imposed defocus. AB - The eyes of growing chicks adjust to correct for myopia (eye relatively long for the focal length of its optics) or hyperopia (eye relatively short for the focal length of its optics). Eyes made functionally hyperopic with negative spectacle lenses become myopic and long, whereas eyes made functionally myopic with positive spectacle lenses become hyperopic and short. We report here that these compensatory growth adjustments occur not only in normal eyes but also in eyes unable to accommodate (focus) because of lesions to the Edinger-Westphal nuclei. Thus, at least in chicks, accommodation is not necessary for growth that reduces refractive errors during development, and may not be necessary for the normal control of eye growth. PMID- 2271447 TI - Topographic organization of the retinocollicular projection in the neonatal rat. AB - The topographic order of the retinocollicular projection in the rat was examined from birth until maturity. Small, localized deposits of rhodamine-filled latex microspheres were placed into the superior colliculus at different locations. To minimize labeling fibers of passage deposit sites were typically, although not exclusively, placed into the caudal-lateral pole of the colliculus. Examination of the area and density of labeled cells in the retinae of these animals led to the following conclusions: (1) At each age examined, the location of the majority of labeled cells was observed to be in appropriate topographic register with the deposit site in the superior colliculus. (2) Confirming the work of previous investigators, errors in topographic projection were observed. These were present in both the contralateral and ipsilateral retinae and decreased with increasing postnatal age. The mature pattern was present by P10. (3) Quantitatively, the number of retinal ganglion cells terminating nontopographically within the colliculus constituted a relatively minor proportion of the total number of labeled cells in both retinae. It is concluded that the majority of the retinal ganglion cells make topographically appropriate terminations within the superior colliculus during development. PMID- 2271448 TI - Time-dependent differential effects of cobalt ions on rod- and cone-driven responses in the isolated frog retina. AB - The effects of cobalt ions on 502-nm rod- and 575-nm cone-driven components of the b-wave of the electroretinogram were studied in the isolated frog retina. Addition of 100-150 microM cobalt initially caused a suppression of rod-driven responses and an enhancement of cone-driven responses. In the continued presence of cobalt, however, the rod-driven responses gradually recovered and the cone driven responses became suppressed. These concentrations of cobalt had no effect on the rod- and cone-driven mass receptor potentials which were isolated in the presence of 4 mM glutamate. At higher concentrations of cobalt (1 mM or greater), both rod- and cone-driven b-wave responses were eliminated and there was no recovery in the continued presence of cobalt. The results suggest that cobalt has markedly different, time-dependent effects on signal transmission from rods and cones to second-order cells. PMID- 2271449 TI - A correlative study of the physiology and morphology of the retinotectal pathway of the perch. AB - The anatomy and physiology of the retinotectal pathway of the perch was investigated using physiological and histological techniques. Massed responses of the optic nerve to single shocks exhibited five distinct peaks. Single-unit responses to shocks indicate two groups of fast fibers correlating well with peaks I and II of the massed response. The flash-evoked response in nerve and tectum has three major phases (PSPI-III), with a marked low-threshold fast component. Patterns of flash-evoked response from single fibers vary, but the responses of fast transient fibers coincide with the timing of PSPI, and longer latency groups with PSPII-III. Units reflexly activated by efferents were also seen, and 12% of units were photically inexcitable. Surprisingly, few fibers responded well to a scanned spot light, unlike tectal cells, and receptive fields were often large (greater than 70 deg). ON/OFF responses, evoked either by whole field or local illumination, were much commoner than pure ON or OFF responses. Effects of electrical stimulation or cautery of the tectum on the flash-evoked response of fiber bundles, via the efferents were marginal, but repetitive stimulation or section of the optic nerve produced clear-cut deficits in the slow components of the flash-evoked response of the nerve. Stimulation of the eighth nerve produced a complex long-latency, large-amplitude response in the optic nerve. The fiber spectrum of the optic nerve taken from electron micrographs revealed the presence of a relatively small group (less than 1%) of thick fibers with diameters between 3 microns and 10 microns that could be correlated with fast responses recorded from the optic nerve, and the remainder with axon diameters down to 0.2 microns providing the slow responses. The distribution of cell-body diameters from sectioned and wholemount material indicated a marked distinction between small and large ganglion cells. The total number of fibers in the nerve was estimated 868,840. PMID- 2271450 TI - Visual tracking of moving targets by freely flying honeybees. AB - The ability of freely-flying honeybees to track moving targets was examined by training them to collect a reward on a target, and then videotaping their approach to the target while it was in motion. Training experiments were carried out with several groups of bees, using various colors for the target and the background. Computer-aided frame-by-frame analysis of video recordings was used to plot the instantaneous positions of the target, as well as the position and orientation of the approaching bee in three dimensions. The results show that bees are perfectly capable of tracking moving targets and landing on them. When the distance of the target is greater than 15 cm, approaching bees correct for angular deviations of the target from the midline, both in the horizontal and in the vertical plane. In either plane, the input variables that are important to the tracking system seem to be (1) the angular bearing of the target with respect to the midline, and (2) the angular velocity of the target with respect to the eye. The tracking control system tends to orient the bee such that the target is located frontally, at an angle of ca. 35 deg below the bee's long axis. The chromatic properties of tracking behavior were investigated by employing combinations of colors for the target and background such that the boundary between the target and the background presented a contrast that was visible either only to the green-sensitive receptors of the bee's eye, or only to the blue-sensitive receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271451 TI - Neural elements in the pineal complex of the frog, Rana esculenta, I: Centrally projecting neurons. AB - The pineal complex of anuran amphibians is a directly photosensory organ, encompassing both an extracranial portion, the frontal organ, and an intracranial portion, the pineal organ proper. The projection neurons of the frontal organ respond differentially according to the wavelengths of the light stimuli. The pineal organ, on the other hand, functions mainly as a luminosity meter. Most of its centrally projecting neurons respond to all increases in ambient illumination with decreases in spontaneous firing of action potentials, although some neural units in the pineal organ may respond according to wavelength. This difference in responses to light stimulation may be reflected in the neural organization of the two parts of the pineal complex. In the present study, we have analyzed the morphology of the projection neurons of the frontal and pineal organs of the frog, Rana esculenta, by backfilling of the neurons with horseradish peroxidase through their cut axons. In the pineal organ, several types of centrally projecting neurons were observed: peripherally situated unipolar and multipolar neurons, the dendrites of which extend into a superficial axon plexus that surrounds the pineal epithelium; smaller unipolar, bipolar, or multipolar neurons situated close to the central pineal tract; and radially oriented bipolar neurons, with short dendritic processes oriented towards the lumen of the pineal organ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271452 TI - Behavioral determination of the spatial selectivity of contrast adaptation in cats: some evidence for a common plan in the mammalian visual system. AB - An aftereffects paradigm was used to behaviorally measure contrast sensitivity of cats to gratings of three different test spatial frequencies after adaptation to gratings of various spatial frequencies, contrasts, and durations. Post adaptation reductions in sensitivity occurred even after short periods of adaptation (less than 7 s) and could be as large as 1.0 log unit under some conditions. The magnitude of the adaptation effect varied monotonically with (1) adaptation grating contrast, (2) duration, and (3) the contrast sensitivity for the test grating. Average half-width (at half-height) of the spatial-frequency tuning curves constructed from the data was 1.4 octaves, and was not dependent upon the level of adaptation or the spatial frequency of the test grating. Post adaptation psychometric functions of the cats showed reduced slopes and maxima suggesting that, unlike humans, in cats apparent contrast grows more slowly with increases in physical contrast after contrast adaptation. All of the characteristics observed are in excellent agreement with electrophysiologically measured properties of neurons in striate cortex of cats. In addition, there was a remarkable similarity of the cat tuning functions, both in shape and bandpass, to those measured in man with a similar paradigm suggesting that (1) the two visual systems are sufficiently similar to make the cat a useful spatial vision model and (2) there is a common functional plan to all mammalian visual systems despite significant anatomical differences between species. PMID- 2271453 TI - Wavelength-dependent temporal properties of retinal horizontal cells in turtles. AB - Electrical responses of luminosity horizontal cells (L cells) to monochromatic stimuli were analyzed by intracellular recordings in the retinas of the freshwater turtle (Pseudemys scripta elegans) and of the sea turtle (Chelonia mydas mydas). Light intensity, duration, and wavelength were varied to assess temporal effects. For a given intensity of monochromatic light, response amplitude increased with stimulus duration until maximum amplitude occurred at a specific duration. This suprathreshold metric of temporal integration is called here summation time, and it is wavelength-dependent. L cells always had some level of red-sensitive cone input, although in some cells inputs from green- and blue-sensitive cones were also observed. For these latter cells, summation times were shorter for 640-nm than for 540-nm or 450-nm lights. These results were most evident in cells that received dominant inputs from blue- or green-sensitive cones. Responses of some other L cells were almost completely dominated by inputs from red-sensitive cones. Summation times of these cells were not wavelength dependent. But when these inputs also included green-sensitive cones, shorter summation times were obtained to 640-nm light than to 540-nm light, even though dominant inputs were still from red-sensitive cones. These results, obtained from both retinal and 3,4-dehydroretinal photopigment systems, are consistent with reported observations in Pseudemys scripta elegans that show linear responses of red-sensitive cones to have shorter integration times and times-to-peak than green-sensitive cones. Responses from horizontal cells dominated by blue sensitive cone inputs were the most sensitive of all; they also had the longest summation times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271454 TI - Representation of the ipsilateral visual field in the transition zone between areas 17 and 18 of the cat's cerebral cortex. AB - The representation of the visual field in the architectonically defined transition zone between areas 17 and 18 of cat cerebral cortex was assessed by recording the activities and plotting the receptive fields of neurons at 2327 sites along 148 electrode penetrations made in 19 cats. The results show that the transition zone contains a significant representation of the ipsilateral visual hemifield although not all elevations in the visual field are represented to the same extent. The shape of the field region represented resembles an hour glass, for the region represented is narrowest on the 0-deg horizontal meridian and increasingly wider at progressively more positive and negative elevations. When receptive-field centers are considered, the extent of the representation reaches to -2.5 deg on the 0-deg horizontal meridian and to 10 or more degrees towards the field periphery. When receptive-field areas are considered, the representation at the 0-deg horizontal meridian extends to -3.6 deg and to beyond 20 deg at other elevations. In contrast, the visual-field representations in flanking areas 17 and 18 are essentially limited to the contralateral hemifield. The presence of a distinct representation of part of the ipsilateral hemifield in the transition zone suggests that the zone may have connections distinctly different from those of the adjacent areas. The observations bear on the problems of understanding the visual pathways in hypopigmented cats and binocular disparity mechanisms about the midline. PMID- 2271455 TI - Receptive fields of neurons at the confluence of cerebral cortical areas 17, 18, 20a, and 20b in the cat. AB - The activity of neurons was recorded extracellularly at the junction of visual cortical areas 17, 18, 20a, and 20b in the cat. The receptive fields of these neurons were striking for their size, which ranged from a diameter of more than 40 deg of visual angle to the complete visual field of the contralateral eye. It is speculated that these large receptive fields may be generated by perturbations in the individual maps as the four areas merge together. PMID- 2271456 TI - Centrifugal pathways to the retina: which way does the "searchlight" point? AB - This commentary extends the review by Hiroyuki Uchiyama (1989) entitled "Centrifugal pathways to the retina: influence of the optic tectum" Visual Neuroscience 3, 183-206. A further scrutiny is made of the topography of the isthmo-retinal projection of the pigeon, which provides the most fully investigated example of a retinopetal projection. It is suggested that the topographical organization in this system is compatible with it's input being derived from the lower visual field (and upper retina) and it's output being directed to the horizon and lower retina. This is another form of attentional hypothesis for the centrifugal pathway, compatible with a role in ground feeding, and is testable by current tracing techniques in neurobiology. PMID- 2271457 TI - Distribution of GABA-immunoreactive amacrine cell synapses in the inner plexiform layer of macaque monkey retina. AB - The distribution patterns of GABA immunoreactive (+) and immunonegative (-) amacrine cell synapses and profiles in the inner plexiform layer (IPL) were analyzed in three macaque monkey retinas using postembedding electron-microscopic (EM) immunogold cytochemistry. Synapses and profiles were counted at 5% intervals throughout the IPL depth in three EM montages (total area = 6509 microns 2), with 0% depth at the inner nuclear layer/IPL border. Nearly 70% of all amacrine synapses were GABA+, and they contacted all major classes of neurons that arborize in the IPL: bipolars (45%), ganglion cells (25%), and GABA+ (20%) and GABA- (10%) amacrines. A major relationship was seen between GABA+ amacrine processes and bipolar terminals: 76% of all amacrine-to-bipolar synapses were GABA+, and 82% of bipolar output dyads contained at least one GABA+ amacrine. GABA+ amacrine profiles (N = 2455) were concentrated in three wide bands at IPL depths of 0-25%, 40-60%, and 75-100%, corresponding to the dense bands seen with light-microscopic immunocytochemistry. In contrast, GABA+ amacrine synapses (N = 1081) were distributed evenly throughout the IPL depth, rather than being confined to the three dense bands. GABA- amacrine synapses (N = 516) were concentrated at 40% and 60% depths. Each category of amacrine output synapses had a characteristic pattern of stratification in the IPL. GABA+ amacrine-to-bipolar synapses occurred throughout the IPL but were most frequent at 20% and 80% IPL depths, where the dendrites of midget cone bipolars arborize (Polyak, 1941). In contrast, GABA+ amacrine-to-ganglion cell synapses were concentrated at 30% and 70% IPL depths, near the dendritic arborizations of parasol ganglion cells (Watanabe & Rodieck, 1989). GABA+ synapses onto bipolars and amacrines were also concentrated at the level of rod bipolar terminals. GABA+ amacrines must play significant but different roles in ON and OFF midget and parasol pathways as well as the rod pathway. PMID- 2271458 TI - Independent eye movements in the turtle. AB - In order to evaluate the normal eye movements of the turtle, Pseudemys scripta elegans, the positions of each eye were recorded simultaneously using two search coil contact lenses. Optokinetic nystagmus (OKN) was strikingly unyoked in this animal such that one eye's slow-phase velocity was substantially independent of that of the other eye. On the other hand, the fast-phase motions of both eyes occurred more or less in synchrony. An eye's slow-phase gain is primarily dependent on the direction and velocity of the stimulus to that eye. Using monocular stimuli, the highest mean gain (0.54 +/- 0.047; mean +/- standard error of mean) occurred using temporal-to-nasal movement at 2.5 deg/s. The mean OKN gain for nasal-to-temporal movement was only 0.13 +/- 0.015 at that velocity. Additionally, using the optimal monocular stimulus (temporal-to-nasal stimulation at 2.5 deg/s) only drove the occluded eye to move nasal-to-temporally at 0.085 deg/s, equivalent to a "gain" of only 0.034 +/- 0.011. The binocular OKN gain during rotational stimuli was higher than monocular gain, especially during nasal to-temporal movement at high velocities. Also the difference in slow-phase eye velocity between the two eyes was smaller during binocular rotational stimuli. In contrast, when each eye simultaneously viewed its temporal-to-nasal stimulus at an equal velocity, two behaviors were observed. Often, OKN alternated between an animal's left eye and right eye. Occasionally, both eyes moved at equal but opposite velocities. These behavioral data provide a quantitative baseline to interpret the properties of the retinal slip information in the turtle's accessory optic system. Those properties are similar to the behavior of the turtle in that both are tuned to direction and velocity independently for each eye (Rosenberg & Ariel, 1990). PMID- 2271459 TI - A burst of differentiation in the outer posterior retina of the eleven-week human fetus: an ultrastructural study. AB - Many studies on human retinal development have cited the third gestational month as a period when the posterior retina undergoes rapid differentiation and maturation, including a lining up of cone precursors. Ultrastructural data on the posterior retina during the third month are very limited, and totally lacking for the cone monolayer. We have examined two human fetal retinas between ten and 11 gestational weeks. Before the appearance of the cone monolayer, the outer neural retina consists of a homogeneous population of undifferentiated neuroblasts. Mitotic figures are still evident, even posteriorally. There is no outer plexiform layer (OPL). The interface of neural retina to retinal pigment epithelium (RPE) is largely featureless. By 11 weeks, the posterior retina has a thin OPL that separates the many rows of cells in the developing inner nuclear layer from the single tier of macular cone precursors. The RPE monolayer consists of cuboidal cells whose apical surface elaborates ridges of cytoplasm and branched processes that project into the subretinal space. The large, cuboidal cones are linked to each other and Muller cells at the outer limiting membrane. They show definitive signs of the structural polarity typical of vertebrate photoreceptors. Their apical cytoplasm contains many organelles common to the inner segment, while the basal cytoplasm has synaptic ribbons and vesicles, and receives invaginating contacts from processes in the OPL neuropil arising from differentiating second-order neurons. Lateral cone surfaces are mutually underlain by large subsurface cisterns. PMID- 2271460 TI - The retinae of Prototherian mammals possess neuronal types that are characteristic of non-mammalian retinae. AB - This study has shown that the retinae of Prototherian (egg-laying) mammals possess two neuronal types that are present in non-mammalian retinae, but absent or morphologically different in the retinae of Eutherian (placental) mammals. First, endogenous serotonin-like immunoreactivity has been localized in a population of presumptive amacrine cells in the platypus retina, the first such report in a mammalian retina. Second, the protein kinase C-immunoreactive (PKC IR) bipolar cells in the echidna retina appear similar to the PKC-IR bipolars in the chicken retina, in that their dendrites give rise to a Landolt's club and their axons are multistratified. By contrast, the PKC-IR rod bipolar cells in the rabbit and in the brushtail possum, a Metatherian (marsupial) mammal, have no Landolt's clubs and their axons form terminal lobes in the innermost stratum of the inner plexiform layer. PMID- 2271461 TI - Properties of area 17/18 border neurons contributing to the visual transcallosal pathway in the cat. AB - In a series of physiological experiments, a total of 203 neurons at the Area 17/18 border were recorded with a callosal link either demonstrated by antidromic or transsynaptic activation from stimulating electrodes located in the homotopic contralateral hemisphere (CH), or in the splenial segment of the corpus callosum (CC). Forty-four percent of the transcallosal cells could also be driven from stimulating electrodes in or just above the lateral geniculate nucleus (OR1). The majority (69%) of transcallosal neurons were classifiable as belonging to the complex family (B and C cells) and most of these were found in the supragranular laminae and in lamina 4A. The ocular dominance distribution of transcallosal cells was trimodal, consisting of roughly equal numbers of monocularly dominated and binocularly balanced neurons. Estimates of conduction time and synaptic delay were obtained for neurons driven from CH, CC, and from OR1, and in most instances the response latency was short enough to suggest a monosynaptic input from either the ipsi- or contra-lateral hemisphere. The distribution of transcallosal conduction times showed that S cells, as a class, had significantly faster conduction than cells of the complex family but otherwise there was no obvious signs of multimodality in the distribution curve. An analysis of the synaptic delays in transcallosal activation produced a mean of 0.6 to 0.7 ms but some were too short to be consistent with a transsynaptic drive, suggesting that some cells with an antidromic drive may have been included in the transsynaptic category. Results are interpreted in terms of the contribution made by the corpus callosum to stereoscopic vision. PMID- 2271462 TI - Distribution of uncrossed and crossed retinofugal axons in the cat optic nerve and their relationship to patterns of fasciculation. AB - The course of optic axons that take different routes at the chiasm have been traced through horizontally sectioned optic nerves in the cat, after unilateral injections of horseradish peroxide into the optic tract. Behind the eye and for most of the course of the nerve, nearly all of the axons that remain uncrossed at the chiasm are located in a retinotopically appropriate position, in the lateral aspect of the nerve. However, in the most caudal segment of the nerve an increasing proportion of these axons are located in regions that are retinotopically inappropriate. Just before the nerve joins the chiasm, uncrossed axons can be found across the full medio-lateral extent of the nerve, although there is still a relative increase in their density laterally. Labeled axons that cross at the chiasm course in a relatively parallel manner along the greater proportion of the nerve. However, in the caudal segment of the nerve their relative positions change and they appear to course in an irregular manner. This occurs where the uncrossed projection becomes increasingly more widespread. Axons in the optic nerve are grouped into fascicules. This pattern of organization also changes in the caudal region of the nerve. Although clear fascicular patterns are present along the greater part of the nerve, they become progressively less distinct caudally. The change in the pattern of fasciculation occurs over the same region of the nerve as the relative changes in axon trajectory and distribution. These results demonstrate that irrespective of chiasmatic route, optic axons in the cat are reorganized in the caudal segment of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271463 TI - The 1990 John J. Bonica lecture. Acute pain therapy--whose responsibility? PMID- 2271464 TI - The 1990 John J. Bonica lecture. The role of the anesthesiologist in managing postoperative pain. PMID- 2271465 TI - Personal reflections on 50 years of obstetric anesthesia. PMID- 2271466 TI - Effects of intravenous test dose epinephrine on fetal sheep during acute fetal stress and acidosis. AB - Small IV doses of epinephrine (epi; 5.0-20.0 micrograms), similar to those advocated for epidural test dosing, cause a significant though transient (3 minutes) reduction in uterine blood flow in pregnant ewes but no subsequent adverse effect on the mature, unstressed fetus. The purpose of this study was to investigate the acute effects on the mature fetus of a maternal IV test dose of 12.5 mg bupivacaine and 50.0 micrograms fentanyl with or without 16.5 micrograms epi in the presence of acute placental insufficiency and fetal asphyxia. Two minutes after dosing and for 15 minutes thereafter, no changes were observed in maternal heart rate (HR), mean arterial pressure (MAP) or arterial blood gas values and catecholamine concentrations other than a statistically significant doubling in epi levels after epi dosing. Mildly (mean arterial pH, 7.23) and severely (mean pH, 6.87) acidotic fetuses differed with respect to arterial pO2, pCO2 and catecholamine values, but in neither group were any changes observed after maternal dosing. Under the conditions of acute fetal stress and acidosis produced in this experiment, inclusion of epi 16.5 micrograms in an epidural test dose does not significantly affect the HR, MAP, aortic flow, blood gases or catecholamine levels of the mature fetal sheep when injected intravenously. PMID- 2271467 TI - Transarterial techniques are not effective for subclavian perivascular block. AB - Although transarterial techniques have been commonly used for axillary block, results with these techniques have not been previously described for subclavian perivascular block. We studied the efficacy and complications of two types of arterial techniques for subclavian perivascular block. In Group 1 (n = 10), the subclavian perivascular injection was made after withdrawing the needle from the subclavian artery (top of artery), and in Group 2 (n = 8), the injection was made after advancing through the subclavian artery (bottom of artery). The local anesthetic used was lidocaine 1.5% with epinephrine 1:200,000 in a volume determined by the formula [ml = (height in inches divided by 2) + 5]. Both techniques were associated with a low incidence (50% or less) of anesthesia throughout the brachial plexus dermatomes. Sixty percent of patients in Group 1 and 63% of patients in Group 2 required supplemental blocks. In view of the low incidence of anesthesia and the frequent need for supplementation, additional patients were not enrolled in the study. Complications associated with the technique included hematoma (12-20%), recurrent laryngeal nerve block (10-25%), Horner's syndrome (0-20%) and phrenic nerve block (75-80%). Despite the relatively high dose of lidocaine used, serum lidocaine levels remained well below the toxic range. PMID- 2271468 TI - A double-blind comparison of 0.5% bupivacaine and 0.75% ropivacaine administered epidurally in humans. AB - In an attempt to compare equipotent doses of epidurally administered bupivacaine and ropivacaine, 44 healthy patients, aged 18-70 years, undergoing lower extremity orthopedic procedures were studied in a randomized, double-blind manner. Twenty-one patients received a single epidural injection of 20 ml 0.5% bupivacaine at the L23 or L34 interspace and 23 patients received 20 ml 0.75% ropivacaine in a similar manner. Onset of and recovery from sensory anesthesia and motor block were recorded. No significant differences were found between the two anesthetic groups except for time to two-segment regression. Maximum block height (median (range] was T4 (T2-T8) and T5 (T2-L1) for bupivacaine and ropivacaine, respectively, and maximum motor block scores were 4 (2-6) and 4 (0 6) using the modified Bromage scale. Times to maximum height of sensory block for bupivacaine and ropivacaine, respectively, were 28 +/- 12 and 28 +/- 13 minutes; times to onset of block to T12 were 6 +/- 4 and 9 +/- 10 minutes; times to onset of maximum motor block were 32 +/- 17 and 47 +/- 29 minutes; times to two-segment regression were 2.7 +/- 0.8 and 3.4 +/- 1.0 hours (p less than 0.05); times to regression to T12 level were 4.8 +/- 0.9 and 4.7 +/- 0.95 hours; times to total recovery of sensation were 6.5 +/- 0.9 and 6.6 +/- 1.0 hours, and times to recovery of motor function were 4.4 +/- 0.9 and 4.1 +/- 0.9 hours. In two instances (both with bupivacaine), anesthesia was judged clinically inadequate. PMID- 2271469 TI - Identification of the anterior psoas sheath as a landmark for lumbar sympathetic block. AB - This clinical report demonstrates that identification of the psoas muscle via contrast media injection under fluoroscopy and the subsequent tenting and puncture of the psoas fascia with a 6-inch 22-gauge needle is a definite aid in the correct placement of the needle for lumbar sympathetic block. In ten patients in whom this technique was used, the needle position was subsequently proven to be correctly placed in all cases. The authors conclude that this method is a valuable adjunct in fluoroscopy-guided lumbar sympathetic block. PMID- 2271470 TI - Plasma concentrations after high doses of mepivacaine with epinephrine in the combined psoas compartment/sciatic nerve block. AB - A combination of psoas compartment block and sciatic nerve block was performed with a total dose of 731.5 mg mepivacaine (55 ml, 1.33%) with epinephrine (1:600,000) in patients scheduled for orthopedic surgery on one leg. In 20 patients, arterial blood samples were collected at timed intervals over a 6-hour period to determine the mepivacaine plasma concentration. In all patients, good sensory and motor blocks were obtained and no analgesics were required during surgery. Despite the high dose of mepivacaine, the plasma concentrations stayed below 6.0 micrograms/ml, with one exception, although no clinical signs of local anesthetic toxicity were observed. Plasma pharmacokinetic variables of mepivacaine were as follows: Cmax: 4.22 mg.l-1 (SD, 1.28); Tmax: 0.99 hours (SD, 0.76); T1/2: 3.25 hours (SD, 1.12); CL 0.55 1.hour-1.kg-1. PMID- 2271471 TI - Anesthesia for cesarean delivery in patients with herpes simplex virus type-2 infections. AB - Some concerns exist regarding the use of regional anesthesia for patients with active genital herpes simplex virus type-2 (HSV) infections undergoing cesarean delivery. Previous studies have reported the safe use of epidural anesthesia in these patients; there are no reports of the use of spinal anesthesia in this setting. We performed a 6-year retrospective survey of 169 patients delivered by cesarean delivery because of HSV infection. One hundred sixty-four of these patients had the diagnosis of secondary infection and five had the diagnosis of primary infection. Fifty-nine patients received general anesthesia, 75 received spinal anesthesia, and 35 received epidural anesthesia. One patient who was diagnosed with primary herpes and who received spinal anesthesia had a transient postpartum neurologic deficit; the etiology of this deficit was not clearly related to the anesthetic technique. No patients with secondary infection had septic or neurologic complications related to the anesthetic. Both spinal and epidural anesthesia appear to be safe alternatives for patients with secondary HSV infections undergoing cesarean delivery. PMID- 2271473 TI - Continuous assessment scale for regional anesthesia. PMID- 2271472 TI - Post dural puncture headache and continuous spinal anesthesia. PMID- 2271474 TI - Don't forget chloroprocaine for IVRA. PMID- 2271475 TI - Ephedrine as a marker of intravascular injection in laboring parturients. PMID- 2271476 TI - Defect in the integrity of an epidural catheter. PMID- 2271477 TI - Axial dynamic compression plates in the management of complex orbital fractures via transconjunctival orbitotomy. AB - We describe our 4 years' experience using axial dynamic compression plates in the management of 46 zygomatico-orbital and complex infraorbital fractures. Surgical exposure of the fracture sites was accomplished in all cases by transconjunctival orbitotomy with lateral cantholysis. Transconjunctival orbitotomy with lateral cantholysis provides excellent surgical exposure of periorbital fractures, and axial dynamic compression plates are an excellent method for repairing these fractures. PMID- 2271478 TI - Magnetic resonance imaging and computed tomographic scanning of fresh (green) wood foreign bodies in dog orbits. AB - Wooden foreign bodies in the orbit can extend into the intracranial cavity without diagnostic clues from the small eyelid entrance wound, from neurologic examination, and from imaging studies such as ultrasound, plain x-rays, or computed tomography (CT) scans. In cadaver magnetic resonance imaging (MRI) studies, dry wood in the orbit can be seen as a negative or hypointense image in contrast to orbital fat. We studied fresh, green wood in dogs to determine the reliability of CT and MRI scans to image hydrated wood. Wood was placed into each orbit of two dogs. After 24 h the wood was removed from one orbit, but not the other. The dogs were then scanned with CT and MRI. Radiologists were asked to determine if any wood had been left in either or both orbits. The fresh wooden foreign bodies could not be detected despite an intensive effort. MRI does not appear to reliably demonstrate fresh wood in the orbit. MRI can show dry wooden foreign bodies that have not become hydrated, but has not yet been reliable in the clinical situation to rule out the presence of wood in the orbit. PMID- 2271479 TI - The transconjunctival approach to the orbital floor and orbital fat. A prospective study. AB - The transconjunctival approach to the inferior orbit and orbital fat offers the potential advantage of avoidance of scar creation in the lower eyelid skin and anterior lamellae. Complications of this approach, including conjunctival fornix shortening and eyelid margin malposition, have been occasionally reported. We prospectively observed 25 patients undergoing transconjunctival blepharoplasty and orbital floor surgery. Fornix depth, eyelid margin position, and the presence or absence of eyelid retraction were measured preoperatively and at each postoperative visit. No significant permanent change in these parameters was observed. Temporary entropion was observed in two patients; this resolved with conservative treatment. On self-limited suture granuloma was observed. In a subgroup of six patients, the conjunctival incision was closed on one side and left unclosed on the other. No adverse healing was noted on the unclosed side. We conclude that the transconjunctival approach is associated with a low incidence of complications, and that it does not significantly alter the fornix depth or eyelid margin position. A skin incision is avoided. The inferior orbital septum is not violated, greatly reducing the risk of development of lower eyelid retraction. PMID- 2271480 TI - Use of Vicryl (polyglactin-910) mesh implant for correcting enophthalmos and hypo ophthalmos. A study of 16 patients. AB - Vicryl mesh (polyglactin-910) implants were used to reconstruct the orbital floor to correct enophthalmos or hypo-ophthalmos (globe ptosis) in 16 patients. The main advantages of Vicryl mesh over other alloplastic implants is that (a) it is absorbed by host tissue, and, once absorbed, it will not cause long-term complications; (b) it is layered and is cut from folded sheets into the appropriate size, shape, and thickness for the treatment of enophthalmos or hypo ophthalmos; and (c) it is soft and pliable and, therefore, is unlikely to erode orbital structures. We followed all patients for a minimum period of 6 months after surgery and observed no significant adverse reactions to the mesh; 15 of the patients had good surgical results with a mean improvement of 1.4 mm in enophthalmos and 0.6 mm in hypo-ophthalmos. After surgery, one patient with combined medial wall and floor fractures developed enophthalmos that was 2 mm more severe than the degree of preoperative enophthalmos. Vicryl mesh should be considered an alternative to both nonautogenous implants and autogenous grafts in orbital floor fracture repair especially for correction of mild and possibly moderate degrees of enophthalmos and hypo-ophthalmos. PMID- 2271481 TI - Botulinum A toxin injection. Failures in clinical practice and a biomechanical system for the study of toxin-induced paralysis. AB - Botulinum A toxin injection has great utility in the treatment of essential blepharospasm and other facial spasm disorders. Several investigators have noted the failure of botulinum toxin injections to relieve lid spasm in occasional patients and a decrease in effectiveness or duration of effect following multiple injections in other patients. We reviewed the charts of 30 consecutive patients presenting for the evaluation or treatment of facial dystonia. Of 20 patients who had received multiple injections of botulinum toxin, 10 patients were felt to be treatment failures. A new biomechanical system was developed to investigate the duration and degree of paralysis induced in the gastrocnemius muscle of the rat. Animals were treated with four sequential injections at 6-week intervals to the same muscle, resulting in muscle atrophy and an increase in the duration and degree of muscle paralysis, contrary to clinical findings in humans. The review of patient data confirms that, for many patients, repeated injection of botulinum toxin results in a decrease in duration and degree of effect despite an increased toxin dose. An opposite effect was noted in our experimental model because of progressive muscle atrophy. PMID- 2271482 TI - Dermal graft. Alternative to Gunderson flap allows fitting scleral shell over sensitive cornea. AB - Corneal discomfort often prevents the successful wearing of a cosmetic scleral shell. Such sensitive corneas are traditionally covered with a Gunderson conjunctival flap. I describe two patients in whom preexisting severe conjunctival scarring precluded the possibility of developing a Gunderson flap. An alternative procedure in which autogenous split-thickness dermal grafts were sutured over the sensitive cornea was utilized in each patient. The dermal grafts reepithelialized with mucosa within 4 weeks, and both patients were then able to retain an ocular prosthesis without discomfort. I conclude that satisfactory corneal coverage may be obtained with a dermal graft when conjunctival scarring precludes the use of a Gunderson flap. PMID- 2271483 TI - Congenital ptosis in monozygotic twins. AB - A case of concordance for unilateral congenital ptosis in monozygotic twins is presented. The literature on genetics and congenital ptosis is reviewed. A heritability index is calculated for congenital ptosis, based on all current twin data including the present report. A value for the heritability index of 0.75 is found, suggesting a strong hereditary influence for congenital ptosis. We conclude that twin data strongly support a transmissable genetic defect as contributing to the development of congenital ptosis. PMID- 2271484 TI - Traumatic neuroma of the eyelid associated with ptosis. AB - A 17-year-old boy presented with persistent swelling and ptosis of the eyelid after blunt injury. Histologic examination revealed a clinically unsuspected traumatic neuroma. Ptosis and the traumatic neuroma persisted despite two eyelid operations. Traumatic neuroma is rare after blunt trauma; it has not been previously reported in the eyelid. It is important to identify this lesion because complete excision may help to prevent recurrence. PMID- 2271485 TI - Spontaneous hematic cysts of the orbit presenting with acute proptosis. A report of three cases. AB - Three cases of spontaneous hematic cyst of the orbit are described. All cases presented with acute onset of proptosis, conjunctival chemosis, choroidal folds, restricted ocular movement, and optic nerve compression syndrome with very poor vision. A computed tomography scan demonstrated a cystic lesion situated in the upper part of the orbit. Exploration revealed a cyst containing chocolate-colored fluid. Visual recovery was complete in two of three cases. There was no definite history of trauma in all three cases. Chronic hematic cysts have been described recently, but cases with acute onset such as ours have not to our knowledge been described clearly. PMID- 2271486 TI - Chorioretinal folds and a macular hole secondary to craniofacial surgery. AB - Chorioretinal folds have been reported as a result of many intraocular and extraocular inflammatory processes or tumors. Visual loss is usually secondary to a combination of the underlying process and chorioretinal folds involving the macula. We report a patient who developed decreased vision, metamorphopsia, chorioretinal folds, and a lamellar macular hole secondary to global compression by a bone fragment. The chorioretinal folds regressed and his vision stabilized following surgical decompression. Chorioretinal folds and lamellar macular hold formation are previously unrecognized complications of reconstructive craniofacial surgery. PMID- 2271487 TI - Biophysical approach to the determination of the secondary structure of the histone H1 globular region. AB - A possible secondary structure of the globular part of the histone H1 was obtained with a statistical approach based on the GOR method. The results of circular dichroism measurements on the protein were taken into account in order to choose between theoretically equivalent structures. PMID- 2271488 TI - 19F-n.m.r. study of trifluoperazine-S100 protein interaction: effects of Ca2+ and Zn2+. AB - 19F-n.m.r. spectra were measured to investigate the effects of Ca2+ and Zn2+ on the interaction of trifluoperazine (TFP) with three S100 proteins. It was found that TFP binds to S100a and S100ao proteins irrespective of the presence of Ca2+ and Zn2+, while in the presence of Ca2+ the apparent affinity of TFP to the proteins was greater than that in its absence or in the presence of Zn2+. In contrast, the binding affinity of TRP to S100b protein in the presence and absence of metal ions was lower than to S100a and S100ao proteins. These results suggested that TFP binds to each S100 protein in two ways: one is Ca2(+)- or Zn2(+)-dependent specific manner and another is Ca2(+)- or Zn2(+)-independent non specific manner. PMID- 2271489 TI - Surface shear viscometry as a probe of protein-protein interactions in mixed milk protein films adsorbed at the oil-water interface. AB - Time-dependent surface viscosities are reported for films adsorbed from binary mixtures of the proteins alpha-lactalbumin, beta-lactoglobulin and beta-casein. The measurements were made at a planar interface between n-tetradecane and various protein solutions (10(-3) wt% of each protein, pH 7, 25 degrees C) using a Couette-type torsion-wire surface viscometer operating at very low shear-rate. Differences in behaviour between simultaneous and sequential exposure of the pairs of proteins to the interface were investigated. Some experiments were performed with chemically modified beta-lactoglobulin samples whose disulphide bonds had been cleaved and blocked. Displacement of one protein by another (e.g. alpha-lactalbumin by beta-casein) is indicated by a sudden drop in surface viscosity immediately after addition of the second protein. In systems containing beta-lactoglobulin, the long-time surface viscosity is very sensitive to the adsorption time of beta-lactoglobulin prior to addition of the second protein. Blocking the disulphide bonds in beta-lactoglobulin leads to a much faster approach to a steady-state surface viscosity. This is interpreted in terms of a much more rapid unfolding of the disordered molecules of modified beta lactoglobulin at the oil-water interface. We conclude that surface viscosity experiments give useful and sensitive information about competitive adsorption and cooperative interactions in mixed protein films. PMID- 2271490 TI - Conformational transition and polyelectrolyte behaviour of a succinoglycan polysaccharide. AB - We report the chemical characterization and the relationship between the physicochemical properties and conformational change of a succinoglycan polysaccharide produced by Pseudomonas sp, NCIB 11592. The expected chemical structure is confirmed, with a ratio of D-glucose: D-galactose: pyruvate: succinate of 7:1:1:1. The molecular weight of the native form is 4.2 x 10(6) but after a single heating cycle through the disordered state the molecular weight is reduced to 3.0 x 10(6). The polymer has a polymolecularity index of 1.3 in both cases. The conformational change was studied by different methods which enabled us to define the exact nature of the ordered and disordered states. The conformational transition depends on the temperature, the ionic strength and the nature of the counterion. The polyelectrolyte behaviour is in favour of a single chain conformation with an intramolecular helix-coil transition. The enthalpy change during this transition is greater than that expected solely on the basis of the polyelectrolyte contribution. It may be associated with changes in solvation or a rearrangement of water molecules in close association with the polymer. PMID- 2271491 TI - Rheological behaviour of a succinoglycan polysaccharide in dilute and semi-dilute solutions. AB - We report the rheological behaviour of a succinoglycan polysaccharide in dilute and semi-dilute solutions as a function of temperature, ionic strength and the nature of counterion. We have examined the viscosity dependence as a function of molecular weight using samples obtained by ultrasonication. We have also prepared samples lacking succinate substitutes and compared their behaviour with that of the native polymer. In both cases, we observed that, after heating a polymer solution for the first time above the conformational transition temperature, a different ordered state was obtained on cooling. This state had a lower molecular weight and intrinsic viscosity but identical chemical structure and local properties. A role for the side chain in the stabilization of breaks in the backbone is suggested. Nevertheless, a unique curve is obtained for the specific viscosity as a function of the overlap parameter c[eta] for different polymer concentrations of both the native and heated forms. However, different curves are obtained for normal and succinate-free polymers, and the succinate-free polymer is characterized by a lower Huggins constant. PMID- 2271492 TI - Physicochemical studies of two major subpopulations of low density lipoproteins by differential scanning calorimetry and n.m.r. spectroscopy. AB - Two subpopulations, layer 2 (density 1.025-1.029 g/ml) and layer 3 (density 1.032 1.043 g/ml) of low density lipoproteins (LDL) were isolated from fresh human plasma of normal lipidaemic subjects by density gradient ultracentrifugation. Chemical analyses demonstrated the ratios of triglyceride/cholesterol ester decreased with increasing densities of subfractions. These subfractions together with triglyceride-rich lipoproteins (layer 1, density less than 1.019 g/ml) were subjected to physicochemical studies by differential scanning calorimetry (d.s.c.) and nuclear magnetic resonance (n.m.r.) spectroscopy. The average transition temperature (Tt) of layer 2 was 34.20 +/- 0.83 degrees C and that of layer 3 was 37.25 +/- 0.35 degrees C. In addition, many of the layer 3, but not layer 2 and layer 1, samples showed structural alteration and gave rise to an average Tt of 39.18 +/- 1.24 degrees C. The structural alteration could be detected with polarizing light microscopy showing birefringent spherulites at body temperature. The peak Tt values obtained by d.s.c. were in good agreement with those by n.m.r. spectroscopy. These results demonstrate the physicochemical heterogeneity within the LDL density region and suggest that layer 3 subpopulation is much more labile than the others. PMID- 2271493 TI - Comparative study of the precipitation of low density lipoproteins by aortic proteodermatan sulphate and heparin. AB - The aortic proteoglycans and heparin were shown to form insoluble complexes with human low density lipoproteins (LDL). The effect of temperature, polyethylene glycol and ionic strength on the formation of complexes between porcine aortic proteodermatan sulphate (PDS) and LDL has been studied by laser nephelometry and comparisons made with heparin LDL complexes. Turbidity was a nonlinear function of the quantity of LDL precipitated by PDS. The turbidity of aggregates was constant at temperatures between 2 degrees C and 30 degrees C but increased with temperature above 30 degrees C up to 50 degrees C. The formation of insoluble complexes decreased rapidly with increasing NaCl concentration. Polyethylene glycol enhanced the turbidity at 20 degrees C but not at 37 degrees C. It also increased the resistance of complexes to dissociation by increasing ionic strength. The turbidity of heparin--LDL complexes was linearly correlated with the quantity of precipitated LDL. The heparin-LDL aggregates were less sensitive to modification of temperature and ionic strength than the PDS-LDL aggregates. These results suggest that ionic interactions are weaker in PDS-LDL complexes than in the heparin-LDL complexes. Non-coulombic interactions and/or temperature dependent conformational changes may be involved in the stabilization of supramolecular PDS-LDL aggregates. No such interactions or changes appear to be involved in complex formation between heparin and LDL. PMID- 2271494 TI - Conformational analysis of xyloglucans. AB - Xyloglucan isolated from the elongating regions of pea stems was examined using X ray diffraction and energy calculations. The X-ray fibre pattern suggested that the backbone (1----4)-beta-D-glucan takes an extended two-fold helix similar to common cellulose. In order to study side chains (xylosyl or fucosyl-galactosyl xylosyl residues) of the polysaccharide, energetically preferable conformations were searched by calculation of interactions between non-bonded atom pairs. A stepwise calculation for the conformation of fucosyl-galactosyl-xylosyl residue gave 10 allowed area (phi-psi) maps which are useful to deduce xyloglucan conformations of both monocotyledons and dicotyledons in the walls of growing plant cells. PMID- 2271495 TI - The fate of spargana inoculated into the cat brain and sequential changes of anti sparganum IgG antibody levels in the cerebrospinal fluid. AB - To establish an animal model of intracranial sparganosis, the fate and behavior of the experimentally inoculated spargana were observed. A total of 102 scolices of spargana were injected into 22 cat brains, and the cats were sacrificed at 2 weeks, 1 month, 3 months and 6 months after the inoculation. Neurosparganosis was established in 77% of the cats. Of 43 recovered worms, 19 (44%) were located in the subdural or subarachnoid space, 16 (37%) in the brain parenchyme, and 2 (5%) in the lateral ventricle. One was detected at the diploic space of the skull and 5 were outside the cranial cavity. All but one were alive, and had grown tails. They were distributed in the brain parenchyme randomly. There was no place which they could not invade. No adult was found in the intestine. Cerebrospinal fluid (CSF) was collected before inoculation, 1 week, 2 weeks, 1 month, 3 months and 6 months after inoculation. The level of anti-sparganum IgG antibody in CSF measured by ELISA began to increase above the criteria of positivity 1 month after inoculation. Three months after inoculation, the values markedly increased. The present findings reveal that intracranial inoculation of spargana into the brains of cats would be a good animal model of experimental neurosparganosis. PMID- 2271496 TI - [A study on the body fluid antigen of Clonorchis sinensis using immunogold labeling method]. AB - In order to observe the antigenic localization in the tissues of the adult Clonorchis sinensis, immunogold labeling method was applied using serum immunoglobulins (IgG) of either worm-infected rabbits (group I) or antigen immunized rabbits (group II) (by the body fluid obtained from the adult worms). The electron micrographs of the sectioned worm tissue antigens, embedded in Lowicryl HM 20 medium and stained with protein A-gold complex (particle size: 12 nm), were compared between the group I and group II. The gold particles were observed in the interstitial matrix of the worm parenchyma, the epithelial lamellae of the cecum, and the cecal lumen both in group I and II. But the particles were in general more concentrated in group II. The gold particles were not observed on the basal lamina of the tegument or on vitelline glands in group I, while they were highly concentrated on those areas in group II. There were also differences in the antigenicity of interstitial matrix(reacted with group I IgG) and head part(reacted with group II IgG) of the sperm cells in the seminal receptacle. Conclusively, it is suggested that the substances comprising the basal lamina of the tegument or vitelline glands act as specific antigens reacting with antigen(body fluid) immunized rabbit IgG. On the other hand, the substances in the cecal lumen and cecal epithelial lamellae are thought to be the specific antigen that react with the worm-infected rabbit IgG. PMID- 2271497 TI - [Detection of IgG and IgM antibodies with ELISA technique in human trichomoniasis]. AB - The direct wet mount examination of vaginal secretion, widely applied for the diagnosis of Trichomonas vaginalis infection in woman patients, is rapid and economical, however, the sensitivity of this technique is not so high. In this study enzyme-linked immunosorbent assay (ELISA) was employed for the detection of serum anti-T. vaginalis IgG and IgM antibodies from 30 vaginal trichomoniasis patients and 30 non-infected healthy persons. The results were as follows: 1. Serum ELISA-IgG value was 0.37 +/- 0.134 (Mean +/- S.D.) in vaginal trichomoniasis patients and 0.21 +/- 0.054 in healthy controls (p less than 0.005), and the sensitivity and specificity of ELISA for serum IgG antibody were 70.0% and 96.7%, respectively. 2. Serum ELISA-IgM value was 0.33 +/- 0.177 (Mean +/- S.D.) in vaginal trichomoniasis patients and 0.11 +/- 0.051 in healthy controls (p less than 0.005), and the sensitivity and specificity of ELISA for serum IgM antibody were 70.0% and 96.7%, respectively. 3. The ELISA-IgG values showed a significant correlation with ELISA-IgM values (r = 0.77, p less than 0.005). With above results, it is assumed that ELISA is a reliable method for the diagnosis of T. vaginalis infection and simultaneous measurement of serum IgG and IgM with this technique is recommended. PMID- 2271498 TI - [Experimental activation of cryptosporidiosis in mice by immunosuppression]. AB - Cryptosporidium, a coccidian parasite first described by Tyzzer (1907) from a laboratory mouse, has become an important human enteric pathogen causing overwhelming diarrhea especially in immunocompromised patients such as AIDS. This parasite has been reported from over 20 countries and is recognized as a cosmopolitan species. In Korea, however, there has been no report on human as well as animal cryptosporidiosis. This study was performed so as to verify the presence of Cryptosporidium in Korea by activating the parasite from laboratory mice by immunosuppression. Total 65 conventionally-bred ICR mice including a control (5 mice) and 3 experimental groups (20 each) were used for this study. Group I was immunosuppressed with prednisolone injection (1 mg IM, every other day) for 7 weeks. Group II (prednisolone injection and tetracycline administration) and Group III (prednisolone injection and trimethoprim sulfamethoxazole administration) were prepared to observe the effect of antibacterial agents on the activation of cryptosporidiosis. In fecal examinations of mice Cryptosporidium oocysts (4-6 microns in size) were detected from 1 week after the start of immunosuppression and the mice began to die. In H E stained tissue sections of the lower jejunum, numerous very small (2-4 microns), dense, ovoid or spherical, slightly basophilic bodies were seen attached on the free border of mucosal epithelial cells. In scanning and transmission electron microscopic observations, these organisms were identified as various developmental stages of Cryptosporidium. The species is considered to be C. parvum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271499 TI - Experimental life history of Echinostoma cinetorchis. AB - The life history of Echinostoma cinetorchis was completed in the laboratory using Hippeutis cantori as the first and second intermediate host. The incubation for maturation of eggs and hatching of miracidia took 24 days at 28 degrees C. On the 66th day after miracidial challenge, 16 snails were crushed and examined for the presence of E. cinetorchis larvae. The metacercariae were detected in all of the snails, and from three of them were found the rediae and cercariae. The morphological characteristics of the larvae and the experimentally obtained adults were compatible with that of E. cinetorchis. PMID- 2271500 TI - [Chronological observation of intestinal lesions of rats experimentally infected with Echinostoma hortense]. AB - Intestinal histopathological changes due to infection with Echinostoma hortense (Trematoda) were studied in rats after experimental infection with the metacercariae. The metacercariae were obtained from the tadpoles of Rana nigromaculata, a second intermediate host infected in the laboratory. Total 18 albino rats (Sprague-Dawley) were given 200 matacercariae each and sacrificed on the day 1, 3, 7, 11, 22 or 44 post-infection (PI). Segments of the small intestine at 1, 3, 5, 8 and 30 cm posterior to the pylorus (PTP) were resected and studied histopathologically. 1. The flukes were seen to have intruded into the intervillous space in the upper small intestine at early stages (1-3 days PI), however, they were located mainly in the intestinal lumen at later stages (7 44 days PI). The flukes were sucking and destroying the epithelial layers of villi with their oral and ventral suckers. 2. Histopathological changes of the intestine were recognizable in as early as 1-3 days after infection, and the changes became severer as the infection progressed. 3. The intestinal mucosa was histopathologically characterized by villous atrophy and crypt hyperplasia throughout the infection period. Major villous changes were blunting, fusion, severe destruction and loss of epithelial layers of villi. Villous/crypt (V/C) height ratio was remarkably reduced from 3:1 in controls to 1:1 in severely infected animals. In the stroma of villi, inflammatory cell infiltrations, vascular congestion, edema, and/or fibrosis were recognized. The goblet cells were increased in number after 11 days PI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271501 TI - Recovery rate, growth and development of Heterophyopsis continua in experimental chicks. AB - The growth and developmental pattern of H. continua was observed after experimental infection of their metacercariae to chicks. The recovery rate of worms from the chicks at 1 to 28 days post-infection (PI) was 12.8% in average. The rate remained fairly high for early 4 days of infection but decreased thereafter rapidly till 28 days PI. Most of the flukes, 91.9%, were recovered from the ileum of the chicks. In metacercariae, genital organs such as the ovary, testes, seminal vesicle, seminal receptacle and genital sucker were recognizable. At one day PI Mehlis' gland appeared, and at 2 days follicular vitellaria were observed. At 3 days PI, eggs were formed in the uterine tubule and increased in number as the worm grew old. The worms reached 2,990 microns in length and 525 microns in width at 28 days PI. Genital organs developed rapidly in early stages of infection but slowly thereafter to 28 days PI, whereas non-genital organs developed steadily through the infection period. It was proved by this experiment that chicks should be a moderately suitable final host of H. continua. PMID- 2271502 TI - [Intestinal parasite infections among inhabitants in two islands of Tongyeong gun, Kyeongsangnam-do]. AB - This study was performed to evaluate the status of intestinal parasitic infections among the inhabitants in two islands (Chu-do and Doomi-do) of Tongyeong-gun, Kyeongsangnam-do (Province), from August to September, 1989. A total of 189 stool specimens was collected from the inhabitants of 3 villages and examined by Kato's cellophane thick smear and formalin-ether sedimentation techniques. Stoll's dilution egg counting technique was done for the quantitative examination of helminth eggs. The overall positive rate of intestinal parasites was 30.2%. The egg positive rate of Ascaris lumbricoides was 2.1%, that of Trichuris trichiura 24.3%, hookworm 2.1%, Trichostrongylus orientalis 0.5%, Clonorchis sinensis 1.1%, heterophyid 1.6%, and Taenia species 2.6%. The cyst positive rate of Giardia lamblia was 1.6% and that of Entamoeba coli 0.5%. In T. trichiura infection, the egg positive rate of females (29.9%) was much higher than that of males (17.2%). Among the age groups, 10-19 year group showed the highest infection rate, 32.4%. It was revealed that the prevalence of intestinal parasitic infections among the inhibitants of remote islands should be still high in comparison with ever-reported ones in urban or rural areas. PMID- 2271503 TI - Status of intestinal parasite infections in inhabitants of Palmar, Guayas Province, Ecuador. AB - Status of intestinal protozoan and helminthic infections was surveyed in mestizo population living in rural parish of Palmar and its nearby recintos(villages). Three of the surveyed villages were at the Pacific coast and 5 villages were in inner pasture land, located about 100 km west of Guayaquil, the second largest city in Ecuador. One stool sample was examined by one cellophane thick smear for helminth ova and one direct smear stained with Lugol's iodine solution for protozoan cysts. Of 325 persons examined, 66.1% were positive for any ova or cyst. The positive rates were: 18.1% for Ascaris lumbricoides, 19.4% for Trichuris trichiura, 0.6% for hookworm, 3.7% for Hymenolepsis nana, 1.8% for Taenia sp., 19.4% for Entamoeba histolytica, 28.6% for Entamoeba coli, 5.5% for Endolimax nana, 1.5% for Iodamoeba buetschlii, 11.1% for Giardia lamblia and 0.6% for Chilomastix mesnili. Poor supply of potable water was considered the main cause of high prevalence of intestinal protozoan infections. PMID- 2271504 TI - Effects of pyrimidine salvage inhibitors on uracil incorporation of Toxoplasma gondii. AB - Metabolic inhibitors which act in the process of pyrimidine salvage influenced on the uracil incorporation into nucleic acids of Toxoplasma. Inhibitors of dihydrofolate reductase, pyrimethamine and methotrexate, and inhibitors of thymidylate synthase, fluoro-uridine, fluoro-dUMP and fluoro-uracil, diminished isotopic uracil uptake in dose-dependent manners. Azauridine which suppresses de novo pyrimidine biosynthesis did not affect the salvage even in a relatively high dose. These results suggested that the activation of uracil salvage should be closely related with the function of TMP biosynthetic enzymes. The pattern of thymidine uptake had no differences between control HL-60 cells and Toxoplasma infected cells, which did not reflect the specific proliferation of Toxoplasma. It can be exploited to characterize the effects of various compounds related with the proliferation of Toxoplasma, especially its DNA synthesis. PMID- 2271505 TI - [Cytotoxicity of resident and lymphokine-activated mouse peritoneal macrophage against Trichomonas vaginalis]. AB - This study was aimed to observe the direct and lymphokine-activated cell mediated cytotoxic effects against Trichomonas vaginalis by mouse peritoneal macrophages. Cytotoxicity was measured as release of 3H-thymidine from prelabeled protozoa, and tested in U-bottom microtiter plates. A 0.1 ml suspension of labeled protozoa (2 x 10(5)/ml) was placed in each well, followed by 0.1 ml of a suspension containing increasing numbers of peritoneal cells. After a 24 hr incubation at 37 degrees C, 0.1 ml of the supernatant was collected and counted in liquid scintillation counter. Mouse peritoneal macrophages had appreciable level of spontaneous cytotoxicity against T. vaginalis at the effector to target cell ratios from 5:1 to 50:1. Treatment of macrophages with lymphokine, produced by PHA-stimulated spleen cells, increased the cytotoxicity in comparison with resident macrophages against T. vaginalis. The degree of macrophage activation for the killing was not dependent upon the lymphokine concentration. Peritoneal cells adherent to plastic displayed significant levels of cytotoxicity against T. vaginalis. This study indicates that mouse peritoneal macrophages are spontaneously cytotoxic for T. vaginalis and lymphokine increases the cytotoxicity by activating macrophages to kill T. vaginalis. PMID- 2271506 TI - [The effects of antibodies and complement in macrophage-mediated cytotoxicity on metacercariae of the lung fluke, Paragonimus westermani]. AB - Paragonimus westermani is a tissue migrating parasite in the early stage until arriving at lung, and most of the parasites spend their life spans there. Considerable immune responses including activation of macrophages are taken place during the residence of parasites in the host. However, concerning the immunologic defense mechanisms of the host against this parasite, only a few document is available so far. In this study, the cytotoxic effect of peritoneal macrophages under the presence of antibody and/or complement against metacercariae of P. westermani was investigated in vitro. Metacercariae were collected from the crayfish, Cambaroides similis and hatched out in Tyrode solution (pH 7.4). Plastic adherent cells from normal or infected rat (Wistar) peritoneal exudates were used as experimental macrophages. Polyclonal antibodies were obtained from infected rats and a cat. Cat IgG was fractioned with ion exchange chromatography. Fresh rabbit complement was used according to experimental scheme. Various combinations of peritoneal macrophages, normal or infected rat serum, complement and cat IgG were incubated at 36 degrees C in 5% CO2 incubator for 6, 14, 24 and 48 hours. The results obtained were as follows: 1. P. westermani infection activated peritoneal macrophages non-specifically and this activation induced increases of cell adherence and cytotoxicity on metacercariae. 2. In the presence of infected rat serum the antibody-dependent cell-mediated cytotoxicity of peritoneal macrophages on metacercariae was significantly increased and showed a peak at 6-hour incubation. But the cytotoxic effect was markedly reduced after inactivation of complement and heat-labile IgE antibody by the heating of infected serum at 56 degrees C for 30 minutes. 3. The highest cytotoxic effect (100%) of concomitant incubation with IgG and complement showed 24 hours after incubation, although cell adherence was relatively low at 6 hour incubation and 0% at 24-hour incubation. 4. Coordinative functions of complement with serum and IgG were effective in cell adherence and in cytotoxicity, but it is not clear the independent role of complement on the macrophage-mediated cytotoxicity in this study. With these results it is assumed that P. westermani infection can induce the non-specific activation of peritoneal macrophages, and serum antibodies including IgE antibody might enhance the cytotoxicity by macrophages. PMID- 2271507 TI - Effect of adenine arabinoside and alpha-interferon in patients with HBeAg positive chronic active hepatitis. AB - To evaluate and compare the therapeutic efficacy of adenine arabinoside (Ara-A) and alpha-interferon (alpha-INF), 40 patients with biopsy proven chronic active hepatitis B were chosen at random to receive Ara-A (15 mg/Kg, iv, for 10 day) or alpha-INF (3 million unit, sc, every other day for 12 wks) and followed up to 12 months after completion of the therapy. All patients were HBeAg positive. The clinical effects of Ara-A and alpha-INF on seroconversion of HBeAg positive. The clinical effects of Ara-A AND alpha-INF on seroconversion of HBeAg and the levels of serum aminotransferase (ALT) were closely matched and compared with those of the untreated control group (20 cases). Eighteen out of 20 patients received Ara A, 19 patients received alpha-INF, and 19 out of 20 control cases were evaluated at 12 months after completion of treatment. Seroconversion of HBeAg in the alpha INF treated group (19 cases) was observed in seven cases (36.8%), showing a higher seroconversion rate as compared to Ara-A-treated (2/18 cases, 11.1%) and to the control patients (1/19 cases, 5.3%). There were no effects of Ara-A on serum ALT levels in the treated patients compared with the untreated control patients. However there was a remarkable drop in serum ALT levels in the INF treated patients (p less than 0.005, ALT levels at 12 months after treatment; 87.4 +/- 98.8 IU/L) compared to the pretreatment levels (256.7 +/- 175.8 IU/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271508 TI - Influence of gamma-aminobutyric acid on the changes of blood pressure in rats. AB - This is an attempt to investigate the effect of gamma-aminobutyric acid (GABA), a well-known major inhibitory neurotransmitter in the central nervous system, on the blood pressure response in rats and to elucidate the mechanism of its action. GABA injected into a femoral vein of the rat produced a dose-related fall in blood pressure followed by a secondary pressor response. The depressor response evoked by GABA was clearly blocked by pretreatment with chlorisondamine, diazepam and picrotoxin but was unaffected by atropine, prazosin and debrisoquin. GABA induced pressor responses were significantly attenuated by pretreatment with prazosin or picrotoxin, while not affected by atropine, diazepam, debrisoquin and chlorisondamine. These experimental data suggest that GABA causes biphasically depressor and pressor responses in rats, and that the hypotensive activity evoked by GABA may be exerted through activation of GABAergic receptors and hypertensive activity due to stimulation of the adrenergic alpha-receptors, which appears to be associated with GABAergic receptors. PMID- 2271509 TI - Leptospirosis in Chonbuk Province of Korea in 1987. AB - Leptospirosis is a zoonosis with protean clinical manifestations. Its diagnosis requires a high index of suspicion and is confirmed by isolation of the organism or, more commonly, by serologic tests. In the fall of 1987, after severe flooding, we saw 93 patients with leptospirosis, confirmed by a microagglutination test. Thirteen percent of the patients had no clinical or laboratory findings except fever and headache, but the rest had mild to severe manifestations. Jaundice, renal failure, and aseptic meningitis were not common, but pulmonary symptoms, when present, were striking. The mortality rate was 5%. The main cause of death was asphyxiation due to massive hemoptysis from pulmonary hemorrhage and acute respiratory failure. PMID- 2271510 TI - Serum levels of soluble interleukin-2 receptor in pulmonary tuberculosis. AB - It is well known that the activation of cell mediated immunity has an important role in the pathogenesis of pulmonary tuberculosis and the production of the protective immunity against Mycobacterium tuberculosis. During the activation of T-cell by Interleukin-1 released from the macrophage, not only Interleukin-2 but also the soluble Interleukin-2 receptor (sIL-2R) molecule is released into the extracellular fluid. In vitro study reveals that the level of this sIL-2R is well correlated with the degree of activation of the T-cell. We therefore carried out this study to evaluate the significance of the serum IL-2R level in determining the disease activity of pulmonary tuberculosis. The level of sIL-2R was measured by sandwich ELISA method. The level of sIL-2R in 42 patients with bacteriologically -proven active pulmonary tuberculosis (29 far and moderately advanced pulmonary tuberculosis, age: 30.3 +/- 10.3 yrs; 13 minimal pulmonary tuberculosis, age: 34.4 +/- 15.3 yrs) was 1111 +/- 424 mu/ml, which was significantly higher than the normal control group (age: 31.0 +/- 9.9 yrs) (365 +/- 143 mu/ml) and inactive pulmonary tuberculosis group (age: 37.3 +/- 16.9 yrs) (465 +/- 131 mu/ml). But there was no significant difference between 29 patients with advanced pulmonary tuberculosis (1138 +/- 405 mu/ml) and 13 patients with minimal pulmonary tuberculosis (1051 +/- 474 mu/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271511 TI - Endoscopic injection sclerotherapy in patients with bleeding esophageal varices: a retrospective analysis. AB - Endoscopic injection sclerotherapy has been accepted as the procedure of choice for patients with variceal hemorrhage. To evaluate the efficiency of endoscopic injection sclerotherapy in patients with bleeding esophageal varices, we did a retrospective study of 52 patients (non-sclerotherapy group) with bleeding esophageal varices who were admitted to hospitals and did not receive sclerotherapy and of 50 patients (sclerotherapy group) who received sclerotherapy with ethanolamine oleate. The mortality (sclerotherapy group vs. non sclerotherapy group: 18.0% vs. 32.7%) during index hospitalization, the bleeding risk factor (the number of rebleeds per patient/month; 1.56 +/- 2.76 vs. 4.96 +/- 9.99: mean +/- SEM) and the mortality due to bleeding (14.0% vs. 36.5%) were higher in the non-sclerotherapy group than in the sclerotherapy group. Only those in Child's class C who received sclerotherapy had a significantly better survival rate than the non-sclerotherapy group (p less than 0.05). Although formal comparisons were not made because of the retrospective nature of this study, endoscopic injection sclerotherapy is effective and appears to be superior to conventional medical treatments. PMID- 2271512 TI - Urinary plasminogen activator activity in progressive renal failure. AB - The purpose of this study was to discover how functional nephrons produce the plasminogen activator as renal function progresses to renal failure. Urine Plasminogen activator (U-PA) activity was measured by the fibrin plate method in 73 patients with various degrees of renal function deterioration from various underlying diseases and in one healthy individual in order to evaluate the plasminogen activator activity of remnant nephrons. The plasminogen activator activity of the 12 consecutive urine samples from the healthy individual showed that is varied according to the time of day, but there was no circadian rhythm. The urine plasminogen activator activity correlated with the osmolality (r = 0.51, P less than 0.001) and creatinine (r = 0.56, P less than 0.001) of the urine, suggesting that it is concentrated at distal nephrons. The fractional sodium excretion rate (FeNa) increased abruptly when GFR decreased below 25 L/day. This pattern was very similar with the relation between total U-PA activity/GFR and GFR. The correlation between total U-PA activity and FeNa was not significant, but there was a significant direct correlation between total U PA activity/GFR and FeNa (r = 0.775, P less than 0.0001). There was no relationship between the 24-hour urine protein and total U-PA activity or total U PA activity/GFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271513 TI - Pulmonary diffuse alveolar septal amyloidosis--diagnosed by transbronchial lung biopsy. AB - Diffuse alveolar septal involvement is a rare form of pulmonary amyloidosis. Antemortem diagnosis is unusual, and most of the reported cases were diagnosed at autopsy. It has recently been reported that transbronchial lung biopsy via a flexible fiberoptic bronchoscope was a relatively safe method to confirm diffuse alveolar septal amyloidosis. We report a case of pulmonary diffuse alveolar septal amyloidosis confirmed by transbronchial lung biopsy. The patient's chief complaints were dyspnea on exertion and epigastric pain aggravated over a one year period, while a chest roentgenogram showed bilateral diffuse interstitial infiltration. This case also showed nephrotic syndrome, cardiac arrhythmia, congestive heart failure, a tingling sensation in both hands and multiple nodules in the gastrointestinal tracts, suggesting involvement of the kidney, heart, peripheral nerves and gastrointestinal tracts. We propose that when diffuse interstitial lung disease is present with systemic signs such as nephrotic syndrome or cardiac arrhythmia, amyloidosis should be considered as a possible diagnosis. Also, transbronchial lung biopsy may be a useful confirmative diagnostic tool. PMID- 2271514 TI - A case of methimazole-induced acute hepatic failure in a patient with chronic hepatitis B carrier. AB - We report a case of methimazole-induced acute hepatic failure, which occurred 17 weeks after initiation of the drug in a 43-year-old man with hyperthyroidism and hepatitis B surface antigenemia. Postmortem needle autopsy of the liver revealed an established micronodular cirrhosis secondary to hepatitis B with moderate septal/portal inflammation, marked cholestasis and scattered acidophilic bodies. The serum hepatitis B surface antigen (HBsAg) was positive, but reactivation of hepatitis B was unlikely in view of the absence of a serum hepatitis B e antigen (HBeAg) and hepatitis B virus deoxyribonucleic acid (HBV-DNA) and negative stain for HBsAg and hepatitis B core antigen (HBcAg) in the liver tissue. PMID- 2271515 TI - Isolated left coronary ostial stenosis--a case report. AB - A patient with isolated left coronary ostial stenosis proved by coronary angiography is presented. Isolated left coronary ostial stenosis is a rare condition of unknown etiology. Unique clinical and angiographic profiles are discussed in detail with a review of the literature, along with a suggestion of a natural history distinct from that usually seen in atherosclerotic coronary diseases. PMID- 2271516 TI - Regulation of coagulation by a multivalent Kunitz-type inhibitor. PMID- 2271517 TI - Off-resonance rotating frame spin-lattice NMR relaxation studies of phosphorus metabolite rotational diffusion in bovine lens homogenates. AB - The rotational diffusion behavior of phosphorus metabolites present in calf lens cortical and nuclear homogenates was investigated by the NMR technique of 31P off resonance rotating frame spin-lattice relaxation as a means of assessing the occurrence and extent of phosphorus metabolite-lens protein interactions. 31P NMR spectra of calf lens homogenates were obtained at 10 and 18 degrees C (below and above the cold cataract phase transition temperature, respectively) at 7.05 T. Effective rotational correlation times (tau 0,eff) for the major phosphorus metabolites present in cortical and nuclear bovine calf lens homogenates were derived from nonlinear least-squares analysis of R vs omega e (spectral intensity ratio vs precessional frequency about the effective field) data with the assumption of isotropic reorientational motion. Intramolecular dipole-dipole (1H 31P, 31P-31P), chemical shift anisotropy (CSA), and solvent (water) translational intermolecular dipole-dipole (1H-31P) relaxation contributions were assumed in the analyses. In those cases where the limiting value of the spectral intensity ratio failed to reach unity at large offset frequency, a modified formalism incorporating chemical exchange mediated saturation transfer between two sites was used. Values of tau 0,eff for phosphorus metabolites present in the cortex varied from a low of ca. 2 ns [L-alpha-glycero-phosphocholine (GPC)] to a high of 12 ns (alpha-ATP) at 10 degrees C, whereas at 18 degrees C the range was from ca. 1 to 9 ns. For the nucleus the tau 0,eff values ranged from ca. 3 ns (GPC) to 41 ns (Pi) at 10 degrees C; at 18 degrees C the corresponding values ranged from 4 to 39 ns. For PME (phosphomonoester; in lens the predominant metabolite is L alpha-glycerol phosphate) at 18 degrees C evidence was obtained for binding and subsequent exchange with solid like protein domains. The diversity in tau 0,eff values for lenticular phosphorus metabolites is suggestive of differential binding to more slowly tumbling macromolecular species, most likely lens crystallin proteins. Corresponding measurement of tau 0,eff values for the mobile protein fraction present in calf lens cortical and nuclear homogenates at 10 and 18 degrees C, by 13C off-resonance rotating frame spin-lattice relaxation, provided average macromolecular correlation times that were assumed to represent the bound metabolite state. A fast-exchange model (on the T1 time scale), between free and bound forms, was employed in the analysis of the metabolite R vs omega e curves to yield the PMID- 2271518 TI - Extremely thermostable D-glyceraldehyde-3-phosphate dehydrogenase from the eubacterium Thermotoga maritima. AB - D-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Thermotoga maritima, a hyperthermophilic eubacterium, has been isolated in pure crystalline form. The enzyme is a homotetramer with a subunit molecular mass of 37 kDa. The sedimentation coefficient of the native enzyme is 7.3 X 10(-13)s, the isoelectric point is 4.6, and the specific absorption coefficient A1%, 1cm 280nm = 8.4. The enzyme shows extreme thermal stability: differential scanning calorimetry yields a transition temperature (Tm) of 109 degrees C for the NAD-saturated enzyme. Thermal deactivation occurs at T greater than 90 degrees C. The physicochemical characteristics of the enzyme suggest that its gross structure must be very similar to the structure of GAPDHs from mesophilic sources. The amino acid composition does not confirm the known "traffic rules" of thermal adaptation, apart from the Lys----Arg exchange. One reactive and at least two buried SH groups can be titrated with 5,5'-dithiobis(2-nitrobenzoate). The highly reactive SH group is probably the active-site cysteine residue common to all known GAPDHs. The activation energy of the glyceraldehyde 3-phosphate oxidation reaction decreases with increasing temperature. This functional behavior can be correlated with the temperature-dependent changes of both the intrinsic fluorescence and the near-UV circular dichroism; both indicate a temperature-dependent structural reorganization of the enzyme. Hydrogen-deuterium exchange reveals significantly increased rigidity of the thermophilic enzyme if compared to mesophilic GAPDHs at 25 degrees C, thus indicating that the conformational flexibility is similar at the corresponding physiological temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271519 TI - Structure of a novel cofactor containing N-(7-mercaptoheptanoyl)-O-3 phosphothreonine. AB - The cofactor required in the methylcoenzyme M methylreductase reaction was shown to be a large molecule with an Mr of 1149.21 in the free acid form. The cofactor, named MRF for methyl reducing factor, was identified from analyses by fast atom bombardment mass spectrometry and 1H, 13C, and 31P NMR spectroscopy as uridine 5' [N-(7-mercaptoheptanoyl)-O-3-phosphothreonine-P-yl(2-acetamido- 2-deoxy- beta mannopyranuronosyl)(acid anhydride)]-(1----4)-O-2-acetamido-2-deoxy- alpha glucopyranosyl diphosphate. MRF contains N-(7-mercaptoheptanoyl)threonine O-3 phosphate (HS-HTP) [No11, K. M., Rinehart, K. L., Tanner, R. S., & Wolfe, R. S. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 4238-4242] and is linked to C-6 of 2 acetamido-2-deoxymannopyranuronic acid of the UDP-disaccharide through a carboxylic-phosphoric anhydride linkage. It is postulated that this bond is responsible for the instability of the molecule and its hydrolysis during isolation. Analyses of Eadie and Hofstee plots of the methylcoenzyme M methylreductase reaction indicate that MRF has a 6-fold lower Km(app) than HS-HTP and a 50% greater Vmax. This suggests that the UDP-disaccharide moiety may be of importance in the binding of MRF to the enzyme active site. PMID- 2271520 TI - Structure of chymotrypsin-trifluoromethyl ketone inhibitor complexes: comparison of slowly and rapidly equilibrating inhibitors. AB - The peptidyl trifluoromethyl ketones Ac-Phe-CF3 (1) and Ac-Leu-Phe-CF3 (2) are inhibitors of chymotrypsin. They differ in Ki (20 and 2 microM, respectively) as well as in their kinetics of association with chymotrypsin in that 1 is rapidly equilibrating, with an association rate too fast to be observed by steady-state techniques, while 2 is "slow binding", as defined by Morrison and Walsh [Morrison, J. F., & Walsh, C. T. (1988) Adv. Enzymol. Relat. Areas Mol. Biol. 61, 202], with a second-order association rate constant of 750 M-1 s-1 at pH 7.0 [Imperiali, B., & Abeles, R. (1986) Biochemistry 25, 3760]. The crystallographic structures of the complexes of gamma-chymotrypsin with inhibitors 1 and 2 have been determined in order to establish whether structural or conformational differences can be found which account for different kinetic and thermodynamic properties of the two inhibitors. In both complexes, the active-site Ser 195 hydroxyl forms a covalent hemiketal adduct with the trifluoromethyl ketone moiety of the inhibitor. In both complexes, the trifluoromethyl group is partially immobilized, but differences are observed in the degree of interaction of fluorine atoms with the active-site His 57 imidazole ring, with amide nitrogen NH 193, and with other portions of the inhibitor molecule. The enhanced potency of Ac-Leu-Phe-CF3 relative to Ac-Phe-CF3 is accounted for by van der Waals interactions of the leucine side chain of the inhibitor with His 57 and Ile 99 side chains and by a hydrogen bond of the acetyl terminus with amide NH 216 of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271521 TI - Inhibition of chymotrypsin by peptidyl trifluoromethyl ketones: determinants of slow-binding kinetics. AB - A series of seven peptidyl trifluoromethyl ketone (TFK) inhibitors of chymotrypsin have been prepared which differ at the P1 and P2 subsites. Inhibition equilibria and kinetics of association and dissociation with chymotrypsin have been measured. The association rate of Ac-Phe-CF3 was measured at enzyme concentrations between 8 nM and 117 microM in order to examine the relation between the ketone/hydrate equilibrium of trifluoromethyl ketones and the "slow binding" by these inhibitors. The association rate decreases at high enzyme concentrations, indicating that TFK ketone is the reactive species and that conversion of TFK hydrate to ketone becomes rate limiting under these conditions. Inhibitors with hydrophobic side chains at P2 bind more tightly but more slowly to chymotrypsin, indicating that formation of van der Waals contacts between the P2 side chain and the His 57 and Ile 99 side chains of chymotrypsin is a relatively slow process. Inhibitor properties were compared to the Michaelis Menten kinetic constants of a homologous series of peptide methyl ester and peptide amide substrates. Plots of log Ki vs log (kcat/Km) are linear with slopes of 0.65 +/- 0.2, indicating that these inhibitors are able to utilize 65% of the total binding energy between chymotrypsin and its hydrolytic transition state. PMID- 2271522 TI - Protein kinase C interaction with calcium: a phospholipid-dependent process. AB - The calcium-binding properties of calcium- and phospholipid-dependent protein kinase C (PKC) were investigated by equilibrium dialysis in the presence and the absence of phospholipids. Calcium binding to PKC displayed striking and unexpected behavior; the free proteins bound virtually no calcium at intracellular calcium concentrations and bound limited calcium (about 1 mol/mol of PKC) at 200 microM calcium. However, in the presence of membranes containing acidic phospholipids, PKC bound at least eight calcium ions per protein. The presence of 1 microM phorbol dibutyrate (PDBu) in the dialysis buffer had little effect on these calcium-binding properties. Analysis of PKC-calcium binding by gel filtration under equilibrium conditions gave similar results; only membrane associated PKC bound significant amounts of calcium. Consequently, PKC is a member of what may be a large group of proteins that bind calcium in a phospholipid-dependent manner. The calcium concentrations needed to induce PKC membrane binding were similar to those needed for calcium binding (about 40 microM calcium at the midpoint). However, the calcium concentration required for PKC-membrane binding was strongly influenced by the phosphatidylserine composition of the membranes. Membranes with higher percentages of phosphatidylserine required lower concentrations of calcium. These properties suggested that the calcium sites may be generated at the interface between PKC and the membrane. Calcium may function as a bridge between PKC and phospholipids. These studies also suggested that calcium-dependent PKC-membrane binding and PKC function could be regulated by a number of factors in addition to calcium levels and diacylglycerol content of the membrane. PMID- 2271523 TI - L-methionine decarboxylase from Dryopteris filix-mas: purification, characterization, substrate specificity, abortive transamination of the coenzyme, and stereochemical courses of substrate decarboxylation and coenzyme transamination. AB - L-Methionine decarboxylase from the male fern Dryopteris filix-mas has been purified 256-fold from acetone powder extracts to very near homogeneity. The enzyme is membrane-associated and requires detergent for solubilization during the initial extraction. The enzyme is a homodimer of subunit Mr 57,000 and shows a pH optimum at approximately 5.0 with 20 mM (2S)-methionine as substrate. The specific activity, kcat, for methionine is approximately 50 mol s(-1) (mol of active site)(-1) at pH 4.5 and below. A wide range of straight- and branched chain (2S)-alkylamino acids are substrates for the enzyme. The values for the rate of decarboxylation, Vmax, and for the apparent Michaelis constant, Km, however, vary with structure and with the chirality at C-3. The pH dependence of V and V/K has been examined for three substrates: (2S)-methionine, valine, and leucine. Pyridoxal 5'-phosphate (PLP) is required for activity, and in the absence of excess PLP, the activity of the enzyme in incubations reduced with respect to time. The addition of PLP fully restores the activity, indicating that an abortive decarboxylation-transamination accompanies the normal decarboxylation reaction. The occurrence of the abortive reaction was confirmed by showing that [35S]methionine is converted to labeled 3-(methylthio)propionaldehyde while [4' 3H]PLP is converted to labeled pyridoxamine 5'-phosphate (PMP). The decarboxylation of (2S)-methionine gave 3-(methylthio)-1-aminopropane. Preparation of the N-camphanamide derivative of the amine allowed the C-1 methylene protons to be distinguished by 1H NMR spectroscopy. Synthetic samples of the camphanamide were prepared in which each of the C-1 methylene protons was replaced by deuterium. When (2S)-methionine and the C-2 deuteriated isotopomer were incubated with the enzyme in deuterium oxide and protium oxide, respectively, and the products were converted to their camphanamide derivatives and analyzed by 1H NMR spectroscopy, it was evident that decarboxylation occurred with retention of configuration at C-2. When the decarboxylation of six other substrates was studied, examination of the N-camphanamide derivatives of the amines indicated that decarboxylation occurred stereospecifically and, by analogy, with retention of configuration at C-2. When tritiated pyridoxal phosphate was incubated with the enzyme, tritiated pyridoxamine phosphate was formed. Analysis of the chirality of the methylene group at C-4' indicated that, during abortive transamination, protonation occurred from the 4'-si face of the coenzyme, the same stereochemical result as that obtained for several bona fide transaminase enzymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271524 TI - Fern L-methionine decarboxylase: kinetics and mechanism of decarboxylation and abortive transamination. AB - L-Methionine decarboxylase from Dryopteris filix-mas catalyzes the decarboxylation of L-methionine and a range of straight- and branched-chain L amino acids to give the corresponding amine products. The deuterium solvent isotope effects for the decarboxylation of (2S)-methionine are D(V/K) = 6.5 and DV = 2.3, for (2S)-valine are D(V/K) = 1.9 and DV = 2.6, and for (2S)-leucine are D(V/K) = 2.5 and DV = 1.0 at pL 5.5. At pL 6.0 and above, where the value of kcat for all of the substrates is low, the solvent isotope effects on Vmax for methionine are 1.1-1.2 whereas the effects on V/K remain unchanged, indicating that the solvent-sensitive transition state occurs before the first irreversible step, carbon dioxide desorption. The enzyme also catalyzes an abortive decarboxylation-transamination reaction in which the coenzyme is converted to pyridoxamine phosphate [Stevenson, D. E., Akhtar, M., & Gani, D. (1990a) Biochemistry (first paper of three in this issue)]. At very high concentration, the product amine can promote transamination of the coenzyme. However, the reaction occurs infrequently and does not influence the partitioning between decarboxylation and substrate-mediated abortive transamination under steady-state turnover conditions. The partition ratio, normal catalytic versus abortive events, can be determined from the amount of substrate consumed by a known amount of enzyme at infinite time, and the rate of inactivation can be determined by measuring the decrease in enzyme activity with respect to time. For methionine, the values of Km as determined from double-reciprocal plots of concentration versus inactivation rate are the same as those calculated from initial catalytic (decarboxylation) rate data, indicating that a single common intermediate partitions between product formation and slow transamination. The partition ratio is sensitive to changes in pH and is also dependent upon the structure of the substrate; methionine causes less frequent inactivation than either valine or leucine. The pH dependence of the partition ratio with methionine as substrate is very similar to that for V/K. Both curves show a sharp increase at approximately pH 6.25, indicating that a catalytic group on the enzyme simultaneously suppresses the abortive reaction and enhances physiological reaction in its unprotonated state. Experiments conducted in deuterium oxide allowed the solvent isotope effects for the partition ratio and the abortive reaction to be determined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271525 TI - Streptomyces L-methionine decarboxylase: purification and properties of the enzyme and stereochemical course of substrate decarboxylation. AB - L-Methionine decarboxylase from Streptomyces species ATCC 21020 has been purified to near homogeneity, characterized, and compared to the enzyme from the fern Dryopteris filix-mas [Stevenson, D.E., Akhtar, M., & Gani, D. (1990) Biochemistry (first paper of three in this issue)]. The enzyme catalyzes the decarboxylation of a range of alkylamino acid substrates, but the substrate specificity is different from that for the fern enzyme. In accord with the properties of the fern enzyme, the Streptomyces enzyme is also a homodimer of Mr 100,000 +/- 5000 and requires PLP for activity. At low pH where the value of Vmax for both enzymes is maximal and essentially pH independent, kcat for the Streptomyces enzyme with (2S)-methionine as substrate is slightly higher (60 s-1) than the value for the eukaryotic protein (50 s-1). The pH optimum for V/K is much higher than that for the fern enzyme although many features of the pH dependence are similar, including the shape of the curve for the pH dependence of Km. When the decarboxylations of (2S-methionine, (2S)-norleucine, and (2R)-S-ethyl-L-cysteine were conducted on a preparative scale in protium and deuterium oxide, unlabeled and deuteriated amines were formed. 1H NMR spectroscopic analysis of the stereochemistry at C-1 of the camphanamide derivatives of the products [Stevenson, D. E., Akhtar, M., & Gani, D. (1990) Biochemistry (first paper of three in this issue)] indicated that each conversion was stereospecific and occurred with retention of configuration at C-2 of the substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271526 TI - Inhibition of recA protein promoted ATP hydrolysis. 2. Longitudinal assembly and disassembly of recA protein filaments mediated by ATP and ADP. AB - There are at least two major conformations of recA nucleoprotein filaments formed on poly-(deoxythymidylic acid) [poly(dT)], one stabilized by ATP [or adenosine 5' O-(3-thiotriphosphate) (ATP gamma S)] and one stabilized by ADP. Assembly of filaments in the ATP conformation is much faster than assembly in the ADP conformation. A third conformation may be present in the absence of nucleotides. The ATP and ADP conformations are mutually exclusive. When a mixture of ATP and ADP is present, recA protein binding is a function of the ADP/ATP ratio. Complete dissociation is observed when the ratio becomes 1.0-1.5. When a mixture of ATP and ADP is present at the beginning of a reaction, a transient phase lasting several minutes is observed in which the system approaches the state characteristic of the new ADP/ATP ratio. This phase is manifested by a lag in ATP hydrolysis when ATP is added to preformed ADP filaments, and by a burst in ATP hydrolysis in all other cases. More than 15 ATPs are hydrolyzed per bound recA monomer during the burst phase. The transient phase reflects an end-dependent disassembly process propagated longitudinally through the filament, rather than a slow conformation change in individual recA monomers or a slow exchange of one nucleotide for the other. The hysteresis exhibited by the system provides a number of insights relevant to the mechanism of recA-mediated DNA strand exchange. PMID- 2271527 TI - Observation of an anomalously slow association kinetics in the binding of actinomycin D to d(CATGGCCATG). AB - An unusually slow association process which accounts for the bulk of its dichroic changes at 293 nm is observed for d(CAT-GGCC-ATG) when it reacts with actinomycin D (ACTD). This is in contrast to an order of magnitude faster association rates exhibited by oligomers containing a self-complementary tetranucleotide ACTD binding sequence (-TGCA-, -AGCT-, or -CGCG-). The number of drug molecules bound and the melting temperature increase upon ACTD binding are significantly higher for d(CAT-GGCC-ATG) than for other decamers studied. Temperature-dependent spectral measurements of this oligomer in the presence of ACTD suggest additional drug binding prior to denaturation. This particular decamer sequence may be unique, as other decamers containing central -GGCC- sequence and even those differing only by the terminal bases such as d(TAT-GGCC-ATA) and d(GAT-GGCC-ATC) are only weakly binding and do not exhibit such anomalously slow ACTD association kinetics, whereas the dodecamer d(CCAT-GGCC-ATGG) does. CD evidence indicates that, in contrast to the other -GGCC- containing oligomers, both d(CCAT-GGCC ATGG) and its parent decamer exhibit nonstandard B conformations. The observed slow association kinetics and its interesting D/P dependence are rationalized in terms of a model in which the ACTD molecules initially end-stack and distort the oligomer duplex to a favorable ACTD-binding conformation so that intercalation at the central G-C sequence can occur via DNA breathing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271528 TI - Structural consequences of effector binding to the T state of aspartate carbamoyltransferase: crystal structures of the unligated and ATP- and CTP complexed enzymes at 2.6-A resolution. AB - The crystal structure of Escherichia coli aspartate carbamoyltransferase complexed with adenosine 5'-triphosphate (ATP) has been solved by molecular replacement and has been refined to a crystallographic residual of 0.17 at 2.6-A resolution by using the computer program X-PLOR. The unit cell dimensions of this crystal form are a = b = 122.2 A and c = 143.3 A and the space group is P321. Although the c-axis unit cell dimension is approximately 1 A longer than the corresponding dimension of the CTP-ligated P321 crystal form (c = 142.2 A), the ATP-ligated enzyme adopts a T-like quaternary structure. The base moiety of ATP interacts with residues Glu10, Ile12, and Lys60 while the ribose is near Asp19 and Lys60; the triphosphate entity is bound to Lys94, although His20 and Arg96 are nearby. We observe a higher occupancy for ATP in the allosteric site of the R1 regulatory chain in comparison to the occupancy of the R6 allosteric site. These crystallographically independent sites are related by a molecular 2-fold axis. There are other violations of the noncrystallographic symmetry that are similar to those observed in the refined CTP-ligated aspartate carbamoyltransferase structure. These infringements on the molecular symmetry might be the result of intermolecular interactions in the crystal. To ensure the most meaningful comparison with the ATP-ligated structure, we refined the previously reported CTP-bound and unligated structures to crystallographic residuals between 0.17 and 0.18 using X-PLOR. These X-PLOR refined structures are not significantly different from the initial structures that had been crystallographically refined by a restrained least-squares method. After making all possible comparisons between the CTP- and ATP-ligated and the unligated T state structures, we find that the most significant differences are located at the allosteric sites and in small changes in the quaternary structures. At the allosteric site, the binding of CTP and ATP successively enlarges the nucleotide binding cavity, particularly in the vicinity of the base. The changes in the quaternary structure can be characterized by an increase in the separation of the catalytic trimers by approximately 0.5 A as ATP binds to the unligated T structure. On the basis of these structural studies, we discuss the relationships between the conformational differences in the allosteric site and the small changes in the quaternary structure within the T form to the possible mechanisms for CTP inhibition and ATP activation. PMID- 2271529 TI - Crystal structures of aspartate carbamoyltransferase ligated with phosphonoacetamide, malonate, and CTP or ATP at 2.8-A resolution and neutral pH. AB - The R-state structures of the ATP and CTP complexes of aspartate carbamoyltransferase ligated with phosphonoacetamide and malonate have been determined at 2.8-A resolution and neutral pH. These structures were solved by the method of molecular replacement and were refined to crystallographic residuals between 0.167 and 0.182. The triphosphate, the ribose, and the purine and pyrimidine moieties of ATP and CTP interact with similar regions of the allosteric domain of the regulatory dimer. ATP and CTP relatively increase and decrease the size of the allosteric site in the vicinity of the base, respectively. For both CTP and ATP at pH 7, the gamma-phosphates are bound to His20 and are also near Lys94, while the alpha-phosphates interact exclusively with Lys94. The 2'-hydroxyls of both CTP and ATP are near the amino group of Lys60. The pyrimidine ring of CTP makes specific hydrogen bonds at the allosteric site: the NH2 group donates hydrogen bonds to the main-chain carbonyls of Ile12 and Tyr89 and the pyrimidine ring carbonyl oxygen accepts a hydrogen bond from the amino group of Lys60; the nitrogen at position 3 in the pyrimidine ring is hydrogen bonded to a main-chain NH group of Ile12. The purine ring of ATP also makes numerous interactions with residues at the allosteric site: the purine NH2 (analogous to the amino group of CTP) donates a hydrogen bond to the main-chain carbonyl oxygen of Ile12, the N3 nitrogen interacts with the amino group of Lys60, and the N1 nitrogen hydrogen bonds to the NH group of Ile12. The binding of CTP and ATP to the allosteric site in the presence of phosphonoacetamide and malonate does not dramatically alter the structure of the allosteric binding site or of the allosteric domain. Nonetheless, in the CTP-ligated structure, the average separation between the catalytic trimers decreases by approximately 0.5 A, indicating a small shift of the quaternary structure toward the T state. In the CTP- and ATP-ligated R-state structures, the binding and occupancy of phosphonoacetamide and malonate are similar and the structures of the active sites are similar at the current resolution of 2.8 A. PMID- 2271530 TI - Absolute action spectrum of E-FADH2 and E-FADH2-MTHF forms of Escherichia coli DNA photolyase. AB - Escherichia coli DNA photolyase mediates photorepair of pyrimidine dimers occurring in UV-damaged DNA. The enzyme contains two chromophores, 1,5 dihydroflavin adenine dinucleotide (FADH2) and 5,10 methenyltetrahydrofolylpolyglutamate (MTHF). To define the roles of the two chromophores in the photochemical reaction(s) resulting in DNA repair and the effect of DNA structure on the photocatalytic step, we determined the absolute action spectra of the enzyme containing only FADH2 (E-FADH2) or both chromophores (E-FADH2-MTHF), with double- and single-stranded substrates and with substrates of different sequences in the immediate vicinity of the thymine dimer. We found that the shape of the action spectrum of E-FADH2 matches that of the absorption spectrum with a quantum yield phi (FADH2) = 0.69. The action spectrum of E-FADH2 MTHF is also in a fairly good agreement with the absorption spectrum with phi (FADH2-MTHF) = 0.59. From these values and from the previously established properties of the two chromophores, we propose that MTHF transfers energy to FADH2 with a quantum yield of phi epsilon T = 0.8 and that 1FADH2 singlet transfers an electron to or from the dimer with a quantum yield phi ET = 0.69. The chemical nature of the chromophores did not change after several catalytic cycles. The enzyme repaired a thymine dimer in five different sequence contexts with the same efficiency. Similarly, single- and double-stranded DNAs were repaired with the same overall quantum yield. PMID- 2271532 TI - The basic phospholipase A2 from Naja nigricollis venom inhibits the prothrombinase complex by a novel nonenzymatic mechanism. AB - The three phospholipase A2 isoenzymes from Naja nigricollis venom inhibit blood coagulation with different potencies. The strongly anticoagulant basic isoenzyme CM-IV inhibits the prothrombinase complex, whereas the weakly anticoagulant isoenzymes CM-I and CM-II do not. To determine the role of enzymatic activity of the phospholipases in the inhibition of prothrombinase, we varied the time of incubation of each of these isoenzymes with the prothrombinase complex. The inhibition by CM-IV did not increase with time of incubation. CM-I and CM-II failed to inhibit the complex, even with complete hydrolysis of phospholipids in the assay mixture. After alkylation of its active-site histidine, CM-IV lost 97% of its enzymatic activity but retained 60% of its inhibitory potency on prothrombinase. CM-IV also inhibited prothrombinase activity in the absence of phospholipids, whereas CM-I and CM-II did not. The inhibition of the prothrombinase complex by CM-IV is thus not due to its binding to or hydrolysis of phospholipids. The kinetics of CM-IV inhibition of the prothrombinase complex in both the presence and absence of phospholipids was noncompetitive. This inhibition can be explained by binding of CM-IV to either factor Va or Xa, or both, to inhibit the complex. CM-IV differs from previously described nonenzymatic anticoagulants that are proteinase inhibitors or that inhibit the coagulation complexes by interfering with the binding of clotting factors to phospholipids. We conclude that the basic enzyme, CM-IV, inhibits the prothrombinase complex by a novel mechanism independent of enzymatic activity. PMID- 2271531 TI - Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme. AB - Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, we have studied the binding of a variety of insulin analogues to the protease in a solid phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600 fold greater affinity than it does insulin-like growth factor I (25 nM and approximately 16,000 nM, respectively), the first set of analogues studied were hybrid molecules of insulin and IGF I. IGF I mutants [insB1-17,17-70]IGF I, [Tyr55,Gln56]IGF I, and [Phe23,Phe24,Tyr25]IGF I have been synthesized and share the property of having insulin-like amino acids at positions corresponding to primary sites of cleavage of insulin by IDE. Whereas the first two exhibit affinities for IDE similar to that of wild type IGF I, the [Phe23,Phe24,Tyr25]IGF I analogue has a 32-fold greater affinity for the immobilized enzyme. Replacement of Phe-23 by Ser eliminates this increase. Removal of the eight amino acid D chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25 Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271533 TI - Effects on the formation of antenna complex B870 of Rhodobacter capsulatus by exchange of charged amino acids in the N-terminal domain of the alpha and beta pigment-binding proteins. AB - The N-terminal domains of the alpha and beta polypeptides of the B870 antenna complex of Rhodobacter capsulatus are oppositely charged. In both polypeptides two charged amino acids are located close to the N-terminus, and two of them are close to the hydrophobic central domain. To test the hypothesis that charged amino acids in the N-terminus have a function for insertion and assembly of pigment-binding polypeptides, charged amino acids were replaced by amino acids of opposite charge. The results show that an exchange of amino acid positions 3 and 6 in alpha (Lys----Glu) or 2 and 5 in beta (Asp----Lys, Arg) has little effect under semiaerobic conditions on the formation of B870 but the additional exchange of positions 14 and 15 in alpha (Arg----Glu, Asp) and/or 13 and 14 in beta (Asp, Glu----Arg) inhibits strongly under semiaerobic dark and anaerobic light conditions the stable incorporation of the polypeptides into the membrane and the formation of the B870 complex. The mutant U43(pTXAB5) is able to grow without any antenna. PMID- 2271534 TI - Additivity of mutational effects in proteins. PMID- 2271535 TI - Role of tyrosine M210 in the initial charge separation of reaction centers of Rhodobacter sphaeroides. AB - Femtosecond spectroscopy was used in combination with site-directed mutagenesis to study the influence of tyrosine M210 (YM210) on the primary electron transfer in the reaction center of Rhodobacter sphaeroides. The exchange of YM210 to phenylalanine caused the time constant of primary electron transfer to increase from 3.5 +/- 0.4 ps to 16 +/- 6 ps while the exchange to leucine increased the time constant even more to 22 +/- 8 ps. The results suggest that tyrosine M210 is important for the fast rate of the primary electron transfer. PMID- 2271536 TI - Oxidation of monomethoxylated aromatic compounds by lignin peroxidase: role of veratryl alcohol in lignin biodegradation. AB - Lignin peroxidase (LiP), an extracellular heme enzyme from the lignin-degrading fungus Phanerochaete chrysosporium, catalyzes the H2O2-dependent oxidation of a variety of nonphenolic lignin model compounds. The oxidation of monomethoxylated lignin model compounds, such as anisyl alcohol (AA), and the role of veratryl alcohol (VA) in LiP reactions were studied. AA oxidation reached a maximum at relatively low H2O2 concentrations, beyond which the extent of the reactions decreased. The presence of VA did not affect AA oxidation at low molar ratios of H2O2 to enzyme; however, at ratios above 100, the presence of VA abolished the decrease in AA oxidation. Addition of stoichiometric amounts of AA to LiP compound II (LiPII) resulted in its reduction to the native enzyme at rates that were significantly faster than the spontaneous rate of reduction, indicating that AA and other monomethoxylated aromatics are directly oxidized by LiP, albeit slowly. Under steady-state conditions in the presence of excess H2O2 and VA, a visible spectrum for LiPII was obtained. In contrast, under steady-state conditions in the presence of AA a visible spectrum was obtained for LiPIII*, a noncovalent complex of LiPIII and H2O2. AA competitively inhibited the oxidation of VA by LiP; the Ki for AA inhibition was 32 microM. Addition of VA to LiPIII* resulted in its conversion to the native enzyme. In contrast, AA did not convert LiPIII* to the native enzyme; instead, LiPIII* was bleached in the presence of AA. Thus, AA does not protect LiP from inactivation by H2O2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271537 TI - Metabolic origins of urinary unsaturated dicarboxylic acids. AB - Previously, we [Jin, S.-J., & Tserng, K.-Y. (1989) J. Lipid Res. 30, 1611-1619] reported the structures of urinary octenedioic acids occurring in patients with dicarboxylic aciduria. We proposed that these unsaturated octenedioic acids were derived from the oxidation of oleic and linoleic acids. By comparison with synthetic decenedioic acids, we have further identified the higher homologues of unsaturated dicarboxylic acids in urine as cis-5-decenedioic (c5DC10), cis-4 decenedioic (c4DC10), cis-3-decenedioic (cDC10), trans-4-decenedioic, trans-3 decenedioic, cis-5-dodecenedioic (c5DC12), cis-3-dodecenedioic (c3DC12), and trans-3-dodecenedioic acids. The presence of these isomeric decenedioic and dodecenedioic acids in urine is consistent with the proposed metabolic origins. In vitro studies using synthetic unsaturated fatty acids and rat liver homogenates support the proposed metabolic origins of these acids. The following metabolic sequences are proposed for metabolites derived from oleic acid: (route A) cis-5-tetradecenoic acid----cis-5-tetradecenedioic acid----c5DC12----c5DC10--- suberic (DC8)----adipic (DC6); (route B) cis-3-dodecenoic acid----c3DC12--- c3DC10----c3DC8 (cis-3-octenedioic)----DC6. A similar route is derived from linoleic acid: cis-4-decenoic acid----c4DC10----c4DC8 (cis-4-octenedioic)----DC6. The presence of a double bond at position 3, 4, or 5 of fatty acid appears to be rate limiting for further beta-oxidation; therefore, metabolic products with cis 3, cis-4, or cis-5 structure accumulate. Urinary DC8 and DC6 are derived partially from the metabolic degradation of these unsaturated dicarboxylic acids. PMID- 2271538 TI - Affinity of phosphatidylcholine molecular species for the bovine phosphatidylcholine and phosphatidylinositol transfer proteins. Properties of the sn-1 and sn-2 acyl binding sites. AB - Both the phosphatidylcholine transfer protein (PC-TP) and the phosphatidylinositol transfer protein (PI-TP) act as carriers of phosphatidylcholine (PC) molecules between membranes. To study the structure of the acyl binding sites of these proteins, the affinity of 32 distinct natural and related PC molecular species was determined by using a previously developed fluorometric competition assay. Marked differences in affinity between species were observed with both proteins. Affinity vs lipid hydrophobicity (determined by reverse-phase HPLC) plots displayed a well-defined maximum indicating that the acyl chain hydrophobicity is an important determinant of binding of a phospholipid molecule by these transfer proteins. However, besides the overall lipid hydrophobicity, steric properties of the individual acyl chains contribute considerably to the affinity, and PC-TP and PI-TP respond differently to modifications of the acyl chain structure. The affinity of PC-TP increased steadily with increasing unsaturation of the sn-2 acyl moiety, resulting in high affinity for species containing four and six double bonds in the sn-2 chain, whereas the affinity of PI-TP first increased up to two to three double bonds and then declined. These data, as well as the distinct effects of sn-2 chain double bond position and bromination, indicate that the sn-2 acyl chain binding sites of the two proteins are structurally quite different. The sn-1 acyl binding sites are dissimilar as well, since variation of the length of saturated sn-1 chain affected the affinity differently. The data are discussed in terms of the structural organization of the sn-1 and sn-2 acyl binding sites of PC-TP and PI TP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271539 TI - A second-site mutation at phenylalanine-137 that increases catalytic efficiency in the mutant aspartate-27----serine Escherichia coli dihydrofolate reductase. AB - The adaptability of Escherichia coli dihydrofolate reductase (DHFR) is being explored by identifying second-site mutations that can partially suppress the deleterious effect associated with removal of the active-site proton donor aspartic acid-27. The Asp27----serine mutant DHFR (D27S) was previously characterized and the catalytic activity found to be greatly decreased at pH 7.0 [Howell et al. (1986) Science 231, 1123-1128]. Using resistance to trimethoprim (a DHFR inhibitor) in a genetic selection procedure, we have isolated a double mutant DHFR gene containing Asp27----Ser and Phe137----Ser mutations (D27S+F137S). The presence of the F137S mutation increases kcat approximately 3 fold and decreases Km(DHF) approximately 2-fold over D27S DHFR values. The overall effect on kcat/Km(DHF) is a 7-fold increase. The D27S+F137S double-mutant DHFR is still 500-fold less active than wild-type DHFR at pH 7. Surprisingly, Phe137 is approximately 15 A from residue 27 in the active site and is part of a beta-bulge. We propose the F137S mutation likely causes its catalytic effect by slightly altering the conformation of D27S DHFR. This supposition is supported by the observation that the F137S mutation does not have the same kinetic effect when introduced into the wild-type and D27S DHFRs, by the altered distribution of two conformers of free enzyme [see Dunn et al. (1990)] and by a preliminary difference Fourier map comparing the D27S and D27S+F137S DHFR crystal structures. PMID- 2271540 TI - Dihydrofolate reductase from Escherichia coli: probing the role of aspartate-27 and phenylalanine-137 in enzyme conformation and the binding of NADPH. AB - In the absence of ligands, dihydrofolate reductase from Escherichia coli exists in at least two interconvertible conformations, only one of which binds NADPH with high affinity. This equilibrium is pH dependent, involving an ionizable group of the enzyme (pK approximately 5.5), and the proportion of the NADPH binding conformer increases from 42% at pH 5 to 65% at pH 8. The role of specific amino acids in enzyme conformation has been investigated by studying the kinetics of NADPH binding to three dihydrofolate reductase mutants: (i) a mutant in which Asp-27, a residue that is directly involved in the binding of folates and antifolates but not NADPH, has been replaced by a serine, (ii) a mutant in which Phe-137 on the exterior of the molecule and distant from the binding sites has been replaced by a serine, and (iii) a mutant in which both Asp-27 and Phe-137 have been replaced by serines. Mutation of the Asp-27 residue reduces the affinity for NADPH by approximately 7-fold. Kinetic measurements have suggested that this is due mainly to an increase in the rate of dissociation of the initial complex and a slight shift in the enzyme equilibrium to favor the nonbinding conformation. The pH dependence of the conformer equilibrium is also shifted by approximately one pH unit to higher pH (pK approximately 6.5). In addition, the pH profile suggests the involvement of a second ionizable group having a pK of about 8 since, above pH 7, the proportion of the NADPH-binding form decreases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271541 TI - Citrate substitutes for homocitrate in nitrogenase of a nifV mutant of Klebsiella pneumoniae. AB - An organic acid extracted from purified dinitrogenase isolated from a nifV mutant of Klebsiella pneumoniae has been identified as citric acid. H2 evolution by the citrate-containing dinitrogenase is partially inhibited by CO, and by some substrates for nitrogenase. The response of maximum velocities to changes in pH for both the wild-type and the NifV- dinitrogenase was compared. No substantial differences between the enzymes were observed, but there are minor differences. Both enzymes are stable in the pH range 4.8-10, but the enzyme activities dropped dramatically below pH 6.2. PMID- 2271542 TI - Designs for a broad substrate specificity keto acid dehydrogenase. AB - Variations have been made to the structure of the nicotinamide adenine dinucleotide (NAD) dependent L-lactate dehydrogenase from Bacillus stearothermophilus at regions of the enzyme that we believe determine specificity toward different alpha-hydroxy acids (RCHOHCOO-, R = CH3, C2H5, etc.). Two regions of LDH that border the active site (but are not involved in the catalytic reaction) were altered in order to accommodate substrates with hydrophobic side chains larger than that of the naturally preferred substrate, pyruvate (R = CH3). The mutations 102-105GlnLysPro----MetValSer and 236-237AlaAla----GlyGly were made to increase the tolerance for large hydrophobic substrate side chains. The triple and double mutants alone gave little improvement for branched-chain-substituted pyruvates. The five changes together produced a broader substrate specificity alpha-hydroxy acid dehydrogenase, with a 55-fold improved kcat for alpha ketoisocaproate to a value about 1/14 that of the native enzyme for pyruvate. Rational protein engineering enabled coupled changes in enzyme structure to be obtained with greater probability of success than random mutagenesis. PMID- 2271543 TI - The tryptophan synthase bienzyme complex transfers indole between the alpha- and beta-sites via a 25-30 A long tunnel. AB - The bacterial tryptophan synthase bienzyme complexes (with subunit composition alpha 2 beta 2) catalyze the last two steps in the biosynthesis of L-tryptophan. For L-tryptophan synthesis, indole, the common metabolite, must be transferred by some mechanism from the alpha-catalytic site to the beta-catalytic site. The X ray structure of the Salmonella typhimurium tryptophan synthase shows the catalytic sites of each alpha-beta subunit pair are connected by a 25-30 A long tunnel [Hyde, C. C., Ahmed, S. A., Padlan, E. A., Miles, E. W., & Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871]. Since the S. typhimurium and Escherichia coli enzymes have nearly identical sequences, the E. coli enzyme must have a similar tunnel. Herein, rapid kinetic studies in combination with chemical probes that signal the bond formation step between indole (or nucleophilic indole analogues) and the alpha-aminoacrylate Schiff base intermediate, E(A-A), bound to the beta-site are used to investigate tunnel function in the E. coli enzyme. If the tunnel is the physical conduit for the transfer of indole from the alpha-site to the beta-site, then ligands that block the tunnel should also inhibit the rate at which indole and indole analogues from external solution react with E(A-A). We have found that when D,L-alpha-glycerol 3-phosphate (GP) is bound to the alpha site, the rate of reaction of indole and nucleophilic indole analogues with E(A A) is strongly inhibited. These compounds appear to gain access to the beta-site via the alpha-site and the tunnel, and this access is blocked by the binding of GP to the alpha-site. However, when small nucleophiles such as hydroxylamine, hydrazine, or N-methylhydroxylamine are substituted for indole, the rate of quinonoid formation is only slightly affected by the binding of GP. Furthermore, the reactions of L-serine and L-tryptophan with alpha 2 beta 2 show only small rate effects due to the binding of GP. From these experiments, we draw the following conclusions: (1) L-Serine and L-tryptophan gain access to the beta-site of alpha 2 beta 2 directly from solution. (2) The small effects of GP on the rates of the L-serine and L-tryptophan reactions are due to GP-mediated allosteric interactions between the alpha- and beta-sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271544 TI - Mechanism of binding of substrate analogues to tryptophan indole-lyase: studies using rapid-scanning and single-wavelength stopped-flow spectrophotometry. AB - We have examined the binding of oxindolyl-L-alanine, (3R)-2,3-dihydro-L tryptophan, L-homophenylalanine, and N1-methyl-L-tryptophan to tryptophan indole lyase (tryptophanase) from Escherichia coli by using rapid-scanning and single wavelength stopped-flow kinetic techniques. Rate constants for the reactions were determined by fitting the concentration dependencies of relaxations to either linear (pseudo-first-order) or hyperbolic (rapid second-order followed by slow first-order) equations. The reaction with oxindolyl-L-alanine forms a quinonoid intermediate that exhibits a strong peak at 506 nm. This species is formed more rapidly than with the other analogues (84.5 s-1) and is reprotonated very slowly (0.2 s-1). Reaction with L-homophenylalanine also forms a quinonoid intermediate with a strong peak at 508 nm, but the rate constant for its formation is slower (6.9 s-1). The reaction with L-homophenylalanine exhibits a transient intermediate absorbing at about 340 nm that decays at the same rate as the quinonoid peak forms and that may be a gem-diamine. Tryptophan indole-lyase reacts with (3R)-2,3-dihydro-L-tryptophan much more slowly to form a moderately intense quinonoid peak at 510 nm, and a transient intermediate absorbing at about 350 nm is also formed. The species formed in the reaction of N1-methyl-L tryptophan exhibits a peak at 425 nm and a very weak quinonoid absorption peak at 506 nm, which is formed at less than 4 s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271545 TI - Overexpression and mutagenesis of the catalytic domain of dihydrolipoamide acetyltransferase from Saccharomyces cerevisiae. AB - The inner core domain (residues approximately 221-454) of the dihydrolipoamide acetyltransferase component (E2P) of the pyruvate dehydrogenase complex from Saccharomyces cerevisiae has been overexpressed in Escherichia coli strain JM105 via the expression vector pKK233-2. The truncated E2p was purified to apparent homogeneity. It exhibited catalytic activity (acetyl transfer from [1-14C]acetyl CoA to dihydrolipoamide) very similar to that of wild-type E2p. The appearance of the truncated and wild-type E2p was also very similar, as observed by negative stain electron microscopy, namely, a pentagonal dodecahedron. These findings demonstrate that the active site of E2p from S. cerevisiae resides in the inner core domain, i.e., catalytic domain, and that this domain alone can undergo self assembly. The purified truncated E2p showed a tendency to aggregate. Aggregation was prevented by genetically engineered attachment of the interdomain linker segment (residues approximately 181-220) to the catalytic domain. All dihydrolipoamide acyltransferases contain the sequence His-Xaa-Xaa-Xaa-Asp-Gly near their carboxyl termini. By analogy with chloramphenicol acetyltransferase, the highly conserved His and Asp residues were postulated to be involved in the catalytic mechanism [Guest, J. R. (1987) FEMS Microbiol. Lett. 44, 417-422]. Substitution of the sole His residue in the S. cerevisiae truncated E2p, His-427, by Asn or Ala by site-directed mutagenesis did not have a significant effect on the kcat or Km values of the truncated E2p. However, the Asp-431----Asn, Ala, or Glu substitutions resulted in a 16-, 24-, and 3.7-fold reduction, respectively, in kcat, with little change in Km values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271546 TI - Role of the zinc(II) ions in the structure of the three-finger DNA binding domain of the Sp1 transcription factor. AB - The transcription factor Sp1 from Hela cells contains near the C-terminus of this protein of 778 amino acids three contiguous repeats of an amino acid sequence, Cys-X4-Cys-X12-His-X3-His-, typical of the Cys2His2-type zinc-finger DNA binding domain first found in transcription factor TFIIIA. A DNA sequence corresponding to the condons from residue 614 to residue 778 of Spl (encompassing the three zinc-finger motifs) has been cloned and overproduced in Escherichia coli. The fragment of Sp1 containing the C-terminal 165 residues plus 2 from the cloning vector, designated Sp1(167*), can be extracted with 5 M urea and then refolded in the presence of Zn(II) to a protein of specific conformation containing 3.0 +/- 0.2 mol of tightly bound Zn(II)/mol of protein. Gel retardation assays using a labeled 14-bp DNA sequence containing a consensus Sp1 binding site show that the refolded Zn(II) protein specifically recognizes the "GC box" sequence in the presence of a large excess of calf thymus DNA. Treatment of Zn(II)Sp1(167*) with 10 mM EDTA results in removal of Zn(II) and the formation of an apoprotein which does not specifically recognize DNA. Cd(II) can be exchanged for Zn(II) in the refolded protein with full retention of specific DNA recognition. This is the first Cys2His2-type "finger" protein where this substitution has been accomplished. Titration of the Zn(II) protein with 6 mol of p mercuribenzenesulfonate/mol of protein results in the complete release of the three Zn(II) ions. Release of Zn(II) is highly cooperative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271547 TI - Specific interaction of the intermediate filament protein vimentin and its isolated N-terminus with negatively charged phospholipids as determined by vesicle aggregation, fusion, and leakage measurements. AB - The interaction of the intermediate filament protein vimentin and its non-alpha helical N-terminus with phosphatidylserine and phosphatidylinositol small unilamellar vesicles was investigated by measuring vesicle aggregation, fusion, and leakage. While the N-terminus suppressed Ca2(+)-induced fusion of phosphatidylserine vesicles, it caused their rapid aggregation in the absence of Ca2+; at a molar ratio of lipid to polypeptide of 25:3, the polypeptide/lipid complexes precipitated from the reaction mixture. This aggregation was efficiently diminished by NaCl. The phosphatidylinositol vesicles, on the other hand, became leaky when interacting with the N-terminus of vimentin, even at a molar ratio of lipid to polypeptide of 500:1. The leakage of phosphatidylinositol vesicles was suppressed by the addition of Ca2+ or NaCl to the reaction mixture. Intact vimentin also caused leakage of phosphatidylinositol vesicles, at low and high salt concentration. The results indicate specific and differential interactions of the N-terminus of vimentin with various negatively charged lipid species, although there is an electrostatic component common to these interactions. PMID- 2271548 TI - Linked thermal and solute perturbation analysis of cooperative domain interactions in proteins. Structural stability of diphtheria toxin. AB - The temperature and guanidine hydrochloride (GuHCl) dependence of the structural stability of diphtheria toxin has been investigated by high-sensitivity differential scanning calorimetry. In 50 mM phosphate buffer at pH 8.0 and in the absence of GuHCl, the thermal unfolding of diphtheria toxin is characterized by a transition temperature (Tm) of 54.9 degrees C, a calorimetric enthalpy change (delta H) of 295 kcal/mol, and a van't Hoff to calorimetric enthalpy ratio of 0.57. Increasing the GuHCl concentration lowers the transition temperature and the calorimetric enthalpy change. At the same time, the van't Hoff to calorimetric enthalpy ratio increases until it reaches a value of 1 at 0.3 M GuHCl and remains constant thereafter. At low GuHCl concentrations (0-0.3 M), the thermal unfolding of diphtheria toxin is characterized by the presence of two transitions corresponding to the A and B domains of the protein. At higher GuHCl concentrations (0.3-1 M), the A domain is unfolded at all temperatures, and only one transition corresponding to the B domain is observed. Under these conditions, the most stable protein conformation at low temperatures is a partially folded state in which the A domain is unfolded and the B domain folded. A general model that explicitly considers the energetics of domain interactions has been developed in order to account for the stability and cooperative behavior of diphtheria toxin. It is shown that this cooperative domain interaction model correctly accounts for the temperature location as well as the shape and area of the calorimetric curves. Under physiological conditions, domain-domain interactions account for most of the structural stability of the A domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271549 TI - Unfolding-refolding of the domains in yeast phosphoglycerate kinase: comparison with the isolated engineered domains. AB - The role of domains as folding units was investigated with a two-domain protein, yeast phosphoglycerate kinase. Each of the domains was produced independently by site-directed mutagenesis. It has been previously demonstrated by several criteria that these domains are able to fold in vivo into a quasi-native structure [Minard et al. (1989a) Protein Eng. 3, 55-60; Fairbrother et al. (1989) Protein Eng. 3, 5-11]. In the present study, the reversibility of the unfolding refolding process induced by guanidine hydrochloride was investigated for the intact protein and the isolated domains. The transitions were followed by circular dichroism for both domains and the intact protein and by the variations in enzyme activity for the intact protein. Tryptophan residues were used as intrinsic conformational probes of the C-domain. An extrinsic fluorescent probe, N-[[(iodoacetyl)amino]ethyl]-8-naphthylamine-1-sulfonic acid (IAEDANS), was bound to the unique cysteinyl residue Cys97 to observe the conformational events in the N-domain. The unfolding-refolding transitions of each domain in the intact protein and in the isolated domains prepared by site-directed mutagenesis were compared. It was shown that the two domains are able to refold in a fully reversible process. A hyperfluorescent intermediate was detected during the folding of both the isolated C-domain and the intact yeast phosphoglycerate kinase. The stability of each isolated domain was found to be similar, the free energy of unfolding being approximately half that of the intact molecule. PMID- 2271550 TI - Unfolding behavior of human alpha 1-acid glycoprotein is compatible with a loosely folded region in its polypeptide chain. AB - The unfolding of human plasma alpha 1-acid glycoprotein (AGP) induced by heat or guanidine hydrochloride was studied under equilibrium conditions. In thermal unfolding, an intermediate state was detected by the appearance of unusual positive difference absorption bands in the 287-295-nm region, which occurred at lower temperatures than the common denaturation bands at 284 and 291 nm. The formation of this intermediate species apparently involves a local conformational change that perturbs the environment of tryptophyl residues, without affecting the secondary structure of the protein as judged from circular dichroism spectra. On the other hand, denaturation of the glycoprotein induced by guanidine hydrochloride seemed to follow a two-state model with no evidence of any intermediate species; however, the analysis of the transition curve indicated that the change in the accessibility to solvent of amino acid residues of AGP upon unfolding is significantly lower than those observed for other proteins. According to these results, it is proposed that part of the polypeptide chain in native AGP, namely, that from residue 122 to the C-terminus, may be "loosely" folded. PMID- 2271551 TI - Association of a pH-sensitive peptide with membrane vesicles: role of amino acid sequence. AB - The solution properties and bilayer association of two synthetic 30 amino acid peptides, GALA and LAGA, have been investigated at pH 5 and 7.5. These peptides have the same amino acid composition and differ only in the positioning of glutamic acid and leucine residues which together compose 47% of each peptide. Both peptides undergo a similar coil to helix transition as the pH is lowered from 7.5 to 5.0. However, GALA forms an amphipathic alpha-helix whereas LAGA does not. As a result, GALA partitions into membranes to a greater extent than LAGA and can initiate leakage of vesicle contents and membrane fusion which LAGA cannot (Subbarao et al., 1987; Parente et al., 1988). Membrane association of the peptides has been studied in detail with large phosphatidylcholine vesicles. Direct binding measurements show a strong association of the peptide GALA to vesicles at pH 5 with an apparent Ka around 10(6). The single tryptophan residue in each peptide can be exploited to probe peptide motion and positioning within lipid bilayers. Anisotropy changes and the quenching of tryptophan fluorescence by brominated lipids in the presence of vesicles also indicate that GALA can interact with uncharged vesicles in a pH-dependent manner. By comparison to the peptide LAGA, the membrane association of GALA is shown to be due to the amphipathic nature of its alpha-helical conformation at pH 5. PMID- 2271552 TI - Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA. AB - The synthetic, amphipathic peptide GALA undergoes a pH-dependent conformational change and induces leakage of contents from large unilamellar phosphatidylcholine vesicles when in a helical conformation. The kinetics of this process have been investigated over a wide range of pH and lipid and peptide concentrations. Leakage from lipid vesicles is rapidly initiated (within 2 s) when the pH is lowered below 6 and is rapidly terminated when the pH is raised to 7.5. The leakage shows a selectivity to the size of the entrapped molecules and occurs by an all or none mechanism; vesicles either leak or retain all of their contents. Using this experimental data, we have developed a mathematical description of the kinetics of leakage induced by GALA. This model assumes that GALA becomes incorporated into the vesicle bilayer and aggregates to form a pore. Leakage occurs when a critical number of peptides assemble into a supramolecular aggregate in the bilayer. Leakage curves generated at lipid/peptide ratios ranging from 500/1 to 30000/1 can be well described by this formalism. On the basis of the results and the model, we suggest that GALA forms a transbilayer channel composed of 8-12 monomers. The channel diameter ranges from 5 to 10 A. To the best of our knowledge, this is the first model that can predict the leakage kinetics of solutes entrapped in lipid vesicles induced by a pore-forming peptide. The analysis may be of general use in defining the kinetics and state of aggregation of similarly acting peptides and proteins which form multimeric assemblies in membranes. PMID- 2271553 TI - Ganglioside GD3 lactones: polar head group mediated control of the intermolecular organization. AB - The individual properties and intermolecular organization of ganglioside GD3 and of two of its lactone forms (GD3Lactone I and GD3Lactone II) were studied in lipid monolayers. The formation of the first lactone ring in GD3Lactone I eliminates one negative charge and leads to a decrease of the molecular area at all surface pressures. The intermolecular dispersion energy and collapse pressure are higher in GD3Lactone I compared to those in the parent GD3. The surface potential per unit of molecular surface density and the resultant molecular dipole moment are increased in GD3Lactone I with respect to those in GD3 at comparable values of molecular area. In GD3Lactone I the molecular parameters suggest an oligosaccharide chain oriented similarly to that of GD3. On the average, this is perpendicular to the surface, and the resultant polar head-group dipole moment points away from the interface. In GD3Lactone II the negative charges are eliminated, resulting in considerably larger molecular areas than for GD3 and GD3Lactone I at all pressures. The intermolecular dispersion energy of GD3Lactone II is also greatly diminished and the collapse pressure is further increased compared to those of GD3Lactone I. However, the surface potential per unit molecular surface density and the resultant molecular dipole moment of GD3Lactone II are higher than in GD3 Lactone I at similar values of molecular areas. This is probably due to a positive polar head-group dipole moment contribution induced by the additional lactone ring in GD3Lactone II. These changes result from a distorted conformation of the oligosaccharide chain owing to the presence of fused carbohydrate rings which require a greater intermolecular spacing compared to GD3 and GD3Lactone I. PMID- 2271554 TI - Location of the epidermal growth factor binding site on the EGF receptor. A resonance energy transfer study. AB - As a first step toward developing a structural map of key sites on the epidermal growth factor (EGF) receptor, we have used resonance energy transfer to measure the distance of closest approach between the receptor-bound growth factor molecule and lipid molecules at the surface of the plasma membrane. EGF, specifically labeled at its amino terminus with fluorescein 5-isothiocyanate, was used as an energy donor in these experiments, while either octadecylrhodamine B or octadecylrhodamine 101, inserted into plasma membranes isolated from human epidermoid carcinoma (A431) cells, served as the energy acceptors. The energy transfer measurements indicate that the amino terminus of the bound growth factor is about 67 A away from the plasma membrane. On the basis of the dimensions of the EGF molecule, this suggests that EGF binds to a site on its receptor that is a considerable distance (52-82 A) from the surface of these cells. Identical results were obtained under conditions where the receptor functions as an active tyrosine kinase, suggesting that the relative juxtaposition of the EGF binding domain to the membrane surface does not change with receptor autophosphorylation or with the activation of the receptor tyrosine kinase activity. PMID- 2271555 TI - Determination of the secondary structure content of proteins in aqueous solutions from their amide I and amide II infrared bands. Comparison between classical and partial least-squares methods. AB - A method for estimating protein secondary structure from infrared spectra has been developed. The infrared spectra of H2O solutions of 13 proteins of known crystal structure have been recorded and corrected for the spectral contribution of water in the amide I and II region by using the algorithm of Dousseau et al. [Dousseau, F., Therrien, M., & Pezolet, M. (1989) Appl. Spectrosc. 43, 538-542]. This calibration set of proteins has been analyzed by using either a classical least-squares (CLS) method or the partial least-squares (PLS) method. The pure structure spectra calculated by the classical least-squares method are in good agreement with spectra of poly(L-lysine) in the alpha-helix, beta-sheet, and undefined conformations. The results show that the best agreement between the secondary structure determined by X-ray crystallography and that predicted by infrared spectroscopy is obtained when both the amide I and II bands are used to generate the calibration set, when the PLS method is used, and when it is assumed that the secondary structure of proteins is composed of only four types of structure: ordered and disordered alpha-helices, beta-sheet, and undefined conformation. Attempts to include turns in the secondary structure estimation have led to a loss of accuracy. The standard deviation of the difference between X-ray and infrared secondary structure estimates with this method is 4.8% for the alpha-helix, 3.7% for the beta-sheet, and 5.1% for the undefined structure, whereas the regression coefficients are 0.95, 0.96, and 0.56, respectively. The spectra of the calibration proteins were also recorded in 2H2O solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271556 TI - Sequential 1H NMR assignments and secondary structure of the B domain of staphylococcal protein A: structural changes between the free B domain in solution and the Fc-bound B domain in crystal. AB - The recombinant B domain (FB) of staphylococcal protein A, which specifically binds to the Fc portion of immunoglobulin G (IgG), has been investigated with the use of two-dimensional proton nuclear magnetic resonance spectroscopy. All backbone and side-chain proton resonances of FB (60 amino acid residues), except the amide proton resonance of Ala2, were assigned by the sequential assignment procedures by using double-quantum-filtered correlated spectroscopy (DQF-COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), and nuclear Overhauser enhancement spectroscopy (NOESY). On the basis of the NOESY data, three helical regions, Glu9-His19, Glu25-Asp37, and Ser42-Ala55, were identified in the free FB in solution. Existence of two of the three helical regions, Glu9-His19 and Glu25 Asp37, in consistent with the X-ray crystallographic structure of the Fc-bound FB [Deisenhofer, J. (1981) Biochemistry 20, 2361-2370]. By contrast, in the Fc-bound FB as revealed by the X-ray analysis, the Ser42-Glu48 segment is extended and no structural information has been available in the Ala49-Ala55 segment. We suggest that a significant conformation change is induced in the C-terminal region of FB when it is bound to the Fc portion of IgG. PMID- 2271557 TI - Effects of GA mismatches on the structure and thermodynamics of RNA internal loops. AB - UV melting, CD and NMR studies indicate rGCGAGCG and rGCAGGCG from unusually stable duplexes of type a and b. The observed delta G degree 37's in 1 M NaCl are -6.7 and -6.3 kcal/mol, respectively. For the related duplex, c, delta G degree 37 is -4.2 kcal/mol. The predicted delta G degree 37 from nearest-neighbor parameters (formula; see text) for all three duplexes is -4.7 kcal/mol (Freier, S.M., Kierzek, R., Jaeger, J.A., Sugimoto, N., Caruthers, M.H., Neilson, T., & Turner, D.H. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 9373-9377). The results suggest a special interaction in the duplexes containing GA mismatches. Presumably, this is hydrogen bonding between G and A. While the thermodynamics for (rGCGAGCG)2 and (rGCAGGCG)2 are similar, CD and the imino region of the proton NMR spectra indicate their structures are different. In particular, (rGCAGGCG)2 exhibits a CD spectrum typical of A-form geometry with a weak negative band at 280 nm. In contrast, the CD spectrum for (rGCGAGCG)2 has an intense positive band at 285 nm. The NMR spectrum of (rGCAGGCG)2 has a resonance corresponding to a hydrogen-bonded GA mismatch, while for (rGCGAGCG)2 no hydrogen bonded imino proton is observed for the mismatch. The glycosidic torsion angles of the bases in the GA mismatches of (rGCAGGCG)2 and (rCGCAGGCG)2 are anti. Duplexes of type d, where X is A, G, or U, are more stable than e, and the stability differences are similar to those (formula; see text) observed for f versus g. Thus, 3'-dangling ends in this system make contributions to duplex stability that are similar to contributions observed with fully paired duplexes. PMID- 2271558 TI - Kinetic analysis of oligodeoxyribonucleotide-directed triple-helix formation on DNA. AB - Pyrimidine oligonucleotides recognize extended purine sequences in the major groove of double-helical DNA by triple-helix formation. The resulting local triple helices are relatively stable and can block DNA recognition by sequence specific DNA binding proteins such as restriction endonucleases. Association and dissociation kinetics for the oligodeoxyribonucleotide 5'-CTCTTTCCTCTCTTTTTCCCC (bold C's indicate 5-methylcytosine residues) are now measured with a restriction endonuclease protection assay. When oligonucleotides are present in greater than 10-fold excess over the DNA target site, the binding reaction kinetics are pseudo first order in oligonucleotide concentration. Under our standard conditions (37 degrees C, 25 mM Tris-acetate, pH 6.8, 70 mM sodium chloride, 20 mM magnesium chloride, 0.4 mM spermine tetrahydrochloride, 10 mM beta-mercaptoethanol, 0.1 mg/mL bovine serum albumin) the value of the observed pseudo-first-order association rate constant, k2obs, is 1.8 x 10(3) +/- 1.9 x 10(2) L.(mol of oligomer-1.s-1. Measurement of the dissociation rate constant yields an equilibrium dissociation constant of approximately 10 nM. Increasing sodium ion concentration slightly decreased the association rate, substantially increased the dissociation rate, and thereby reduced the equilibrium binding constant. This effect was reversible by increasing multivalent cation concentration, confirming the significant role of multivalent cations in oligonucleotide-directed triple helix formation under these conditions. Finally, a small reduction in association rate, a large increase in dissociation rate, and a resulting reduction in the equilibrium binding constant were observed upon increasing the pH between 6.8 and 7.2. PMID- 2271559 TI - Protein chemical and kinetic characterization of recombinant porcine ribonuclease inhibitor expressed in Saccharomyces cerevisiae. AB - A cDNA encoding porcine ribonuclease inhibitor was used to express this protein in yeast under control of the PHO5 promoter. The recombinant protein was purified to homogeneity with a yield of 0.2 mg/g of yeast cells (wet weight) and was found to be indistinguishable from the inhibitor isolated from porcine liver on the basis of the following criteria: the amino acid composition, the number of free sulfhydryl groups, the molecular weight of the native and the denatured protein, peptide mapping, and amino acid sequence analysis of the N- and C-terminal regions of the protein. A simple method was developed for measuring accurately the slow, tight-biding kinetics of the inhibition of ribonuclease by ribonuclease inhibitor. From the dependence of the observed inhibition constant on the substrate concentration, it could be concluded that RI was competitive with the substrate UpA. The dependence of the observed association rate constant on the substrate concentration was consistent with a two-step mechanism in which the substrate only competed in the second (isomerization) step. The values for the inhibition constant for the inhibition of RNase by the recombinant inhibitor, 67 fM, the association rate constant, 1.5 x 10(8) M-1.s-1, and the dissociation rate constant, 8.3 x 10(-6) s-1, were in good agreement with those obtained for the porcine liver RNase inhibitor. PMID- 2271560 TI - NMR studies of a deoxyribodecanucleotide containing an extrahelical thymidine surrounded by an oligo(dA).oligo(dT) tract. AB - One- and two-dimensional NMR experiments were carried out on a decamer, d (CGCTTTTCGC).d(GCGAAAAGCG), and on the same sequence with the addition of an unpaired thymidine, d(CGCTTTTCGC).d(GCGAATAAGCG), which will be referred to as the T-bulge decamer. Evidence from one-dimensional NOE experiments on the exchangeable protons indicates that the unpaired thymidine is extrahelical. This conclusion is also supported by numerous cross-peaks in the two-dimensional NOESY spectrum of the nonexchangeable protons. Assignments for all of the resonances, with the exception of the H5' and H5" resonances, have been made for both oligonucleotide duplexes through the use of 2D NOESY, COSY, and relayed COSY experiments. Temperature dependence of the methyl resonance chemical shifts indicates that the unpaired thymidine shows unusual behavior compared to other thymidines in the duplex. Two-dimensional NOESY experiments carried out from 5 to 35 degrees C indicate the unpaired thymidine remains extrahelical throughout this temperature range. A similar temperature dependence for the methyl chemical shift is found in the corresponding single-strand d(GCGAATAAGCG). The oligo (dA).oligo(dT) tracts in both the decamer and the T-bulge decamer have structures different from B-form DNA and exhibit NOEs similar to those observed in other oligonucleotides containing A.T tracts. The formation of this unusual A.T tract structure may induce the extrahelical conformation of the unpaired thymidine. PMID- 2271561 TI - Two-dimensional 1H and 31P NMR spectra and restrained molecular dynamics structure of a mismatched GA decamer oligodeoxyribonucleotide duplex. AB - Assignment of the 1H and 31P NMR spectra of a tandem G.A mismatched base pair decamer oligodeoxyribonucleotide duplex, d(CCAAGATTGG)2, has been made by two dimensional 1H-1H and heteronuclear 31P-1H correlated spectroscopy. Unusual downfield 31P resonances have been assigned by a pure absorption phase constant time heteronuclear 31P-1H correlated spectrum to be associated with the phosphates on the 5'- and 3'-sides of the mismatched guanosine residue. JH3'-P coupling constants for each of the phosphates of the decamer were obtained from the 1H-31P J-resolved selective proton-flip 2D spectrum. The two most downfield shifted 31P resonances each appear to consist of two overlapping signals that can be resolved into two distinct doublets with different coupling constants in the J resolved spectrum. This as well as the temperature dependence of the 31P spectra demonstrates that two distinct conformations exist at lower temperatures. By use of a modified Karplus relationship, the C4'-C3'-O3'-P torsional angles (epsilon) were obtained. A linear correlation between 31P chemical shifts and the measured coupling constants is quite good (only when the larger set of coupling constants of the two most downfield 31P signals is included). The 31P chemical shifts as well as the measured coupling constants tend to follow the positional variation seen in other duplexes of interior phosphates resonating more upfield than terminal residues and of interior phosphates exhibiting smaller coupling constants; however, this pattern is disrupted at the site of the mismatch. Modeling and initial NOESY distance restrained molecular mechanics energy minimization and restrained molecular dynamics support previous observations that the mismatched guanine and adenine bases are both in anti conformations. Most significantly, the epsilon backbone torsional angle variaions calculated from the NOESY distance restrained structures are in agreement with both the crystal structure values and the measured JH3'-P coupling constants. PMID- 2271562 TI - 1H NMR assignment and melting temperature study of cis-syn and trans-syn thymine dimer containing duplexes of d(CGTATTATGC).d(GCATAATACG). AB - The preparation and spectroscopic characterization of duplex decamers containing site-specific cis-syn and trans-syn thymine dimers are described. Three duplex decamers, d(CGTATTATGC).d(GCATAATACG), d(CGTAT[c,s]TATGC).d(GCATAATACG), and d(CGTAT[t,s]TATGC).d(GCATAATACG), were prepared by solid-phase phosphoramidite synthesis utilizing cis-syn and trans-syn cyclobutane thymine dimer building blocks (Taylor et al., 1987; Taylor & Brockie, 1988). NMR spectra (500 MHz 2D 1H and 202 MHz 1D 31P) were obtained in "100%" D2O at 10 degrees C, and 1D exchangeable 1H spectra were obtained in 10% D2O at 10 degrees C. 1H NMR assignments for H5, H6, H8, CH3, H1', H2', and H2" were made on the basis of standard sequential NOE assignment strategies and verified in part by DQF COSY data. Comparison of the chemical shift data suggests that the helix structure is perturbed more to the 3'-side of the cis-syn dimer and more to the 5'-side of the trans-syn dimer. Thermodynamic parameters for the helix in equilibrium coil equilibrium were obtained by two-state, all or none, analysis of the melting behavior of the duplexes. Analysis of the temperature dependence of the T5CH3 1H NMR signal gave delta H = 44 +/- 4 kcal and delta S = 132 +/- 13 eu for the trans syn duplex. Analysis of the concentration and temperature dependence of UV spectra gave delta H = 64 +/- 6 kcal and delta S = 178 +/- 18 eu for the parent duplex and delta H = 66 +/- 7 kcal and delta S = 189 +/- 19 eu for cis-syn duplex. It was concluded that photodimerization of the dTpdT unit to give the cis syn product causes little perturbation of the DNA whereas dimerization to give the trans-syn product causes much greater perturbation, possibly in the form of a kink or dislocation at the 5'-side of the dimer. PMID- 2271563 TI - Chemical equilibrium at an antibody binding site: catalytic efficiency defined by a Haldane relationship. AB - This paper describes the first study of a reaction catalyzed in both forward and reverse directions by an antibody. The rates of reversible addition of sulfite to 6-hydroxy-3H-xanthen-3-one (1) and their pH dependence are influenced by a monoclonal antibody to a fluorescein hapten. The antibody is presumed to recognize the two substrates in a chemically productive prereaction complex with a geometry similar to that between the carboxyl group and the xanthenyl group in fluorescein. Equilibria are determined for the reactions in solution and at the antibody combining site from rate constants for the forward and reverse reactions. The solution equilibrium lies in favor of adduct with KA = x 10(7) M-1 at pH 7.5. The corresponding equilibrium at the combining site is much smaller (KAb = 8), and this is attributed to the preferential binding of substrates 1 and sulfite. The magnitude of differential stabilization is determined from the equilibrium constants (2 x 10(6) M-1). Observed rates at low molar standard state are compared to reveal the acceleration of the process at the antibody combining site versus the bimolecular solution reaction. In the associative direction, the rate factor of 1200 may largely be attributed to the entropy savings for the reaction on the catalyst. This analysis serves to illustrate the potential for catalysis by antibodies due from recognition of structural differences between substrates of different energy on a reaction coordinate and suggests a strategy for inducing antibody catalysts that does not presume knowledge of catalytic mechanisms or transition-state structure. PMID- 2271564 TI - The 2.1-A resolution structure of iron superoxide dismutase from Pseudomonas ovalis. AB - The 2.1-A resolution crystal structure of native uncomplexed iron superoxide dismutase (EC 1.15.1.1) from Pseudomonas ovalis was solved and refined to a final R factor of 24%. The dimeric structure contains one catalytic iron center per monomer with an asymmetric trigonal-bipyramidal coordination of protein ligands to the metal. Each monomer contains two domains, with the trigonal ligands (histidines 74 and 160; aspartate 156) contributed by the large domain and stabilized by an extended hydrogen-bonded network, including residues from opposing monomers. The axial ligand (histidine 26) is found on the small domain and does not participate extensively in the stabilizing H-bond network. The open axial coordination position of the iron is devoid of bound water molecules or anions. The metal is located 0.5 A out of the plane of the trigonal ligands toward histidine 26, providing a slightly skewed coordination away from the iron binding site. The molecule contains a glutamine residue in the active site which is conserved between all iron enzymes sequenced to data but which is conserved among all manganese SODs at a separate position in the sequence. This residue shows the same structural interactions in both cases, implying that iron and manganese SODs are second-site revertants of one another. PMID- 2271565 TI - Binding of calcium to SP-A, a surfactant-associated protein. AB - SP-A is a lung-specific pulmonary surfactant-associated protein containing a calcium-dependent carbohydrate recognition domain and collagen-like sequence. The protein is a major component of the extracellular form of surfactant known as tubular myelin. SP-A is thought to influence the surface properties of surfactant lipids and regulate the turnover of extracellular surfactant through interaction with a specific cell-surface receptor. These properties of SP-A are dependent on the presence of calcium. We have estimated calcium binding parameters for SP-A from binding data obtained by equilibrium dialysis and gel permeation chromatography. Our results suggest that each SP-A monomer binds two to three calcium ions in conditions chosen as similar to those found in the alveolar lumen. The binding data are best fit to a model incorporating two calcium binding sites with different affinities. Studies with a fragment of SP-A generated by limited proteolysis suggest the higher affinity site for calcium is located in the noncollagenous carboxy-terminal end of SP-A. This region of SP-A contains a carbohydrate recognition domain homologous to other C-type lectins. The binding of calcium to this region of SP-A causes a conformational change as assessed by a small change in the intrinsic fluorescence spectrum and a marked change in the susceptibility to proteolysis. At physiological calcium concentrations, intact SP A aggregates in a reversible fashion, a property that may be relevant to the formation of tubular myelin. PMID- 2271567 TI - Peptides corresponding to the second repeated sequence in MAP-2 inhibit binding of microtubule-associated proteins to microtubules. AB - Bovine brain high molecular weight microtubule-associated proteins (MAPs) can be displaced from assembled tubules by peptides corresponding to the second of three nonidentical repeated sequences in mouse MAP-2. The octadecapeptide m2 (VTSKCGSLKNIRHRPGGG) can release MAP-1b from MAP-containing microtubules, and the extended second-sequence peptide m2' (VTSKCGSLKNIRHRPGGGRVK) displaces MAP-1a and MAP-1b as well as MAP-2a and MAP-2b. Peptides m2 and m2' stimulate tubulin polymerization in the absence of MAPs or microtubule-stabilizing agents, and m2' acts as a competitive inhibitor of radiolabeled MAP-2 binding. The dissociation constant for MAP-2 binding to taxol-stabilized tubules was 3.4 microM in the absence of m2' and 14 microM in the presence of 1.5 mM of the m2' peptide. We estimate that the inhibition constant for peptide m2' is about 0.5 mM, about 100 times lower than for the Km of MAP-2. These observations suggest that the second repeated sequence in MAP-2 may represent an important recognition site for MAP binding to microtubules and that other structural features within MAP-2 may reinforce the strength of MAP-microtubule interactions. PMID- 2271566 TI - Isolation and partial structural characterization of an equine fibrinogen CNBr fragment that exhibits immunologic cross-reactivity with an A alpha-chain cross linking region of human fibrinogen. AB - Immunochemical studies of equine fibrinogen were conducted to characterize the structural basis for the immunologic cross-reactivity observed between human and equine A alpha chains when employing an antiserum to the 26K, human cyanogen bromide (CNBr) fragment, A alpha 241-476 (CNBr VIII). A 38K, equine CNBr fragment that reacts with this antiserum was isolated from CNBr-digested equine fibrinogen by Sephadex G-100 gel filtration. It was further purified by sequential hydrophobic chromatography on phenyl-Sepharose CL-4B, followed by reversed-phased (C-8) high-performance liquid chromatography (HPLC). NH2-Terminal analysis of the purified fragment, designated EqA alpha CNBr, identified one major sequence whose first three residues, E-L-E, were identical with those of human CNBr VIII. Tryptic and staphylococcal protease digests of the equine fragment were resolved by reversed-phase HPLC (C-4, C-18), and the separated components were characterized by amino acid analysis and automated Edman degradation. A total of 34 tryptic and 20 staph protease peptides yielded sequence information that permitted the alignment of 271 equine residues with residues A alpha 241-517 from the COOH-terminal two-thirds of the human A alpha chain so that 63% of the possible matches were identical. Other features of interest included (1) an amino acid substitution in which the methionine residue at A alpha 476 in the human A alpha chain was replaced by a valine residue, thus accounting, in part, for the larger EqA alpha CNBr fragment obtained from the equine molecule, and (2) a region of striking homology in which 36 successive residues, corresponding to A alpha 428-464 in the human A alpha chain, were identical in both species. These findings, together with available structural data for the COOH-terminal portion of the rat and bovine A alpha chains, indicate that the region corresponding to (human) A alpha 240-517 represents a conserved portion of the fibrinogen molecule. This may, in turn, explain the difficulties encountered when trying to raise monoclonal antibodies to cross-linking regions that are contained within the COOH-terminal two-thirds of the human A alpha chain. PMID- 2271568 TI - Physical properties of glycosyldiacylglycerols: an infrared spectroscopic study of the gel-phase polymorphism of 1,2-di-O-acyl-3-O-(beta-D-glucopyranosyl)-sn glycerols. AB - The thermotropic and barotropic gel-phase polymorphism of a homologous series of saturated, straight-chain beta-D-glucosyldiacylglycerols was studied by Fourier transform infrared spectroscopy. Three spectroscopically distinct lamellar gel phases were detected thermotropically. Upon cooling to temperatures below the gel/liquid-crystalline phase transition temperature, all of these lipids form a metastable L beta gel phase characterized by orientationally disordered all-trans acyl chains. The transformation of the metastable L beta phase to a stable crystalline (Lc2) phase first involves the formation of an intermediate which itself is an ordered crystal-like (Lc1) phase. In the intermediate Lc1 phase, the zigzag planes of the polymethylene chains are nearly perpendicular to one another, and one of the ester carbonyl oxygens is engaged in a strong hydrogen bond, probably to the 2-hydroxyl of the sugar headgroup. The transformation of the Lc1 phase to the Lc2 phase involves a reorientation of the all-trans hydrocarbon chains and is probably driven by the strengthening of the hydrogen bond between the carbonyl ester oxygen and its proton donors. Since a "solid state" reorganization of the acyl chains is an integral part of that process, it tends to become more sluggish as the chain length increases and is not observed with the longer chain homologues (N greater than 16). The spectroscopic characteristics of the most stable gel phases of the odd- and even-numbered members of this homologous series of compounds exhibit only minor differences, indicating that the structures of these phases are generally similar. The barotropic phase behavior of the shorter and longer chain beta-D glucosyldiacylglycerols is also different. Compression of the L beta phase of the shorter chain compounds results in immediate conversion to their stable lc phases, whereas compression of the L beta phase of the longer chains does not. Furthermore, compression of the longer chain compounds may result in the formation of chain-interdigitated bilayers, whereas this is not the case for the shorter chain homologues. We suggest that the gel phase formed by any given homologue at a given temperature or pressure is that which maximizes the sometimes competing requirements for the optimal packing of the sugar headgroups and the hydrocarbon chains. PMID- 2271569 TI - Affinity chromatography purification of angiotensin II receptor using photoactivable biotinylated probes. AB - We have developed biotinylated photoactivable probes that are suitable for covalent labeling of angiotensin II (AII) receptors and the subsequent purification of covalent complexes through immobilized avidin or streptavidin. One of these probes, biotin-NH(CH2)2SS(CH2)2CO-[Ala1,Phe(4N3)8]AII, which contains a cleavable disulfide bridge in its spacer arm and which displays, in its radioiodinated form, very high affinity for AII receptors (Kd approximately 1 nM), proved to be suitable for indirect affinity chromatography of rat liver receptor with facilitated recovery from avidin gels by use of reducing agents. This constituted the central step of an efficient partial purification scheme involving hydroxylapatite chromatography, streptavidin chromatography, and thiopropyl-Sepharose chromatography. SDS-PAGE analysis and autoradiography established the identity of the purified entity (molecular weight 65K) as the AII receptor. Possible ways of completing purification to homogeneity and extrapolation of the protocols to a preparative scale are discussed, as well as the potential contribution of our new probes to the study of the structural properties of angiotensin receptors. PMID- 2271570 TI - Heparin binding domain of antithrombin III: characterization using a synthetic peptide directed polyclonal antibody. AB - Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor that apparently forms covalent complexes with thrombin. The interaction between ATIII and thrombin is enhanced several thousandfold by the glycosaminoglycan, heparin. We have previously proposed that the heparin binding site of ATIII resides within a region extending from amino acid residues 114-156 [Smith, J. W., & Knauer, D. J. (1987) J. Biol. Chem. 262, 11964-11972]. Computer-assisted analysis of this region revealed the presence of a 22 amino acid domain (residues 124-145), part of which shows a strong potential for the formation of an amphipathic helix: hydrophobic on one face and highly positively charged on the other. In the presence studies, polyclonal antisera were generated against a synthetic peptide corresponding to residues 124-145 in native human ATIII. Affinity-purified IgG from these antisera, as well as monovalent Fab's derived from them, specifically blocked the binding of heparin to ATIII. Additionally, occupancy of the heparin binding site by these same monovalent and bivalent IgG's at least partially substituted for heparin, accelerating linkage formation between ATIII and thrombin. These results provide the first immunological evidence that region 124 145 is directly involved in the binding of heparin to ATIII and that an antibody induced conformational change within this region can mediate ATIII activation. PMID- 2271571 TI - Evidence that arginine-129 and arginine-145 are located within the heparin binding site of human antithrombin III. AB - Arginyl residues of human antithrombin III have been implicated to involve in the heparin binding site [Jorgensen, A. M., Borders, C. L., & Fish, W. W. (1985) Biochem, J. 231, 59-63]. We have performed chemical modification of antithrombin with (p-hydroxyphenyl)glyoxal (HPG) in order to determine the locations of these arginine residues. Antithrombin was modified with 12 mM HPG in the absence and presence of heparin (2-fold by weight to antithrombin). In the absence of heparin, about 3-4 mol of arginines/mol of antithrombin were modified within 60 min, and the modification led to the loss of 95% of the inhibitor's heparin cofactor activity as well as heparin-induced fluorescence enhancement and 50% of its progressive inhibitory activity. In the presence of heparin, the extent of modification was diminished by 30% and modified antithrombin retained approximately 70% of its heparin cofactor activity. Peptide mapping and subsequent sequence analysis revealed that selective HPG modification occurred at Arg129 and Arg145 and that their modifications were protected upon binding of heparin to antithrombin. We conclude that Arg129 and Arg145 are situated within the heparin binding site of human antithrombin III. PMID- 2271572 TI - Structure of the retinal chromophore in 7,9-dicis-rhodopsin. AB - Bovine rhodopsin was bleached and regenerated with 7,9-dicis-retinal to form 7,9 dicis-rhodopsin, which was purified on a concanavalin A affinity column. The absorption maximum of the 7,9-dicis pigment is 453 nm, giving an opsin shift of 1600 cm-1 compared to 2500 cm-1 for 11-cis-rhodopsin and 2400 cm-1 for 9-cis rhodopsin. Rapid-flow resonance Raman spectra have been obtained of 7,9-dicis rhodopsin in H2O and D2O at room temperature. The shift of the 1654-cm-1 C = N stretch to 1627 cm-1 in D2O demonstrates that the Schiff base nitrogen is protonated. The absence of any shift in the 1201-cm-1 mode, which is assigned as the C14-C15 stretch, or of any other C-C stretching modes in D2O indicates that the Schiff base C = N configuration is trans (anti). Assuming that the cyclohexenyl ring binds with the same orientation in 7,9-dicis-, 9-cis-, and 11 cis-rhodopsins, the presence of two cis bonds requires that the N-H bond of the 7,9-dicis chromophore points in the opposite direction from that in the 9-cis or 11-cis pigment. However, the Schiff base C = NH+ stretching frequency and its D2O shift in 7,9-dicis-rhodopsin are very similar to those in 11-cis- and 9-cis rhodopsin, indicating that the Schiff base electrostatic/hydrogen-bonding environments are effectively the same. The C = N trans (anti) Schiff base geometry of 7,9-dicis-rhodopsin and the insensitivity of its Schiff base vibrational properties to orientation are rationalized by examining the binding site specificity with molecular modeling. PMID- 2271573 TI - Conformational requirement of signal sequences functioning in yeast: circular dichroism and 1H nuclear magnetic resonance studies of synthetic peptides. AB - Recently, we have designed a series of simplified artificial signal sequences and have shown that a proline residue in the signal sequence plays an important role in the secretion of human lysozyme in yeast, presumably by altering the conformation of the signal sequence [Yamamoto, Y., Taniyama, Y., & Kikuchi, M. (1989) Biochemistry 28, 2728-2732]. To elucidate the conformational requirement of the signal sequence in more detail, functional and nonfunctional signal sequences connected to the N-terminal five residues of mature human lysozyme were chemically synthesized and their conformations in a lipophilic environment [aqueous trifluoroethanol (TFE) or sodium dodecyl sulfate micelles] analyzed by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectroscopy. The helix content of the peptides, including functional (L8, CL10) and nonfunctional (L8PL, L8PG, L8PL2) signal sequences, was estimated from CD spectra to be 40-50% and 60-70%, respectively, indicating that the helical structure is more abundant in the nonfunctional signal sequences. Two-dimensional NMR analyses in 50% TFE/H2O revealed that each peptide adopted a helical conformation throughout the sequence except for a few residues at the N- and C-termini. Furthermore, H-D exchange experiments indicated that the helical structure of the C-terminal region of the functional signal sequences (L8 and CL10) was less stable than that of the nonfunctional signal sequences (L8PL and L8PL2). On the basis of these results, a model was developed in which the functional signal sequence is inserted in the membrane with a helical conformation and the C-terminal helix unraveled in an extended conformational form through an interaction with the signal peptidase. PMID- 2271574 TI - 1H NMR studies of the glucocorticoid receptor DNA-binding domain: sequential assignments and identification of secondary structure elements. AB - Two protein fragments containing the DNA-binding domain (DBD) of the glucocorticoid receptor (GR) have been studied by two-dimensional 1H NMR spectroscopy. The two peptides (93 and 115 residues, respectively) contain a common segment corresponding to residues C440-I519 of the rat GR or residues C421 I500 of the human GR and include two Zn-binding "finger" domains. The structures of this segment are almost identical in the two protein fragments, as judged from chemical shifts and sequential NOE connectivities. More than 90% of all observable 1H resonances within a 71-residue segment encompassing C440-R510 (rat GR) could be sequentially assigned by standard techniques, and stereospecific assignments could be made for the methyl groups in four valine residues within this segment. Sequential NOE connectivities indicate several elements of secondary structure including two alpha-helical segments consisting of residues S459-E469 and P493-G504, a type I reverse turn between residues R479 and C482, a type II reverse turn between residues L475 and G478, and several regions of extended peptide conformation. No evidence for alpha-helical conformation was found within the two putative zinc-finger domains, indicating that the structures of these domains differ from that of TFIIIA-type zinc fingers. The observation of some very slowly exchanging amide protons in the N-terminal (CI) domain of the DBD in combination with slow rotation of the Y452 aromatic ring indicates that this domain has a restricted conformational flexibility compared to the C terminal (CII) domain. We also observe several long-range NOE connectivities within C440-R510, suggesting that the sequential assignments presented here will provide a basis for a complete structure determination of this segment of the GR. PMID- 2271575 TI - Specific binding of lac repressor to linear versus circular polyoperator molecules. AB - Gel shift assays were used to examine the binding of the lactose (lac) repressor to polyoperator DNA molecules. Specific binding was differentiated from nonspecific DNA association by (i) equilibrating repressor-operator complexes below the nonspecific association constant and (ii) demonstrating the effects of the inducer isopropyl beta-D-thiogalactoside (IPTG) on the formation of repressor operator complexes. With the linear polyoperator molecules, all eight operator sites could be simultaneously bound by distinct repressors. However, with circular molecules, the eight operator sites were saturable by repressor only in the nicked circular state and not in the covalently closed circular form. Under the experimental conditions used, there was no evidence of bifunctional repressor binding or loop formation. The results suggest that the conformational perturbation of DNA that occurs upon specific repressor binding was retained in topologically closed molecules and could modify other operator sites so as to make them unavailable for specific binding. PMID- 2271576 TI - Kinetic isotope effect studies on milk xanthine oxidase and on chicken liver xanthine dehydrogenase. AB - The effect of isotopic substitution of the 8-H of xanthine (with 2H and 3H) on the rate of oxidation by bovine xanthine oxidase and by chicken xanthine dehydrogenase has been measured. V/K isotope effects were determined from competition experiments. No difference in H/T(V/K) values was observed between xanthine oxidase (3.59 +/- 0.1) and xanthine dehydrogenase (3.60 +/- 0.09). Xanthine dehydrogenase exhibited a larger T/D(V/K) value (0.616 +/- 0.028) than that observed for xanthine oxidase (0.551 +/- 0.016). Observed H/T(V/K) values for either enzyme are less than those H/T(V/K) values calculated with D/T(V/K) data. These discrepancies are suggested to arise from the presence of a rate limiting step(s) prior to the irreversible C-H bond cleavage step in the mechanistic pathways of both enzymes. These kinetic complexities preclude examination of whether tunneling contributes to the reaction coordinate for the H transfer step in each enzyme. No observable exchange of tritium with solvent is observed during the anaerobic incubation of [8-3H]xanthine with either enzyme, which suggests the reverse commitment to catalysis (Cr) is essentially zero. With the assumption of adherence to reduced mass relationships, the intrinsic deuterium isotope effect (Dk) for xanthine oxidation is calculated to be 7.4 +/- 0.7 for xanthine oxidase and 4.2 +/- 0.2 for xanthine dehydrogenase. By use of these values and steady-state kinetic data, the minimal rate for the hydrogen transfer step is calculated to be approximately 75-fold faster than kcat for xanthine oxidase and approximately 10-fold faster than kcat for xanthine dehydrogenase. This calculated rate is consistent with data obtained by rapid quench experiments with XO. A stoichiometry of 1.0 +/- 0.3 mol of uric acid/mol of functional enzyme is formed within the mixing time of the instrument (5-10 ms). The kinetic isotope effect data also permitted the calculation of the Kd values [Klinman, J. P., & Mathews, R. G. (1985) J. Am. Chem. Soc. 107, 1058-1060] for substrate dissociation, including all reversible steps prior to C-H bond cleavage. Values calculated for each enzyme (Kd = 120 microM) were found to be identical within experimental uncertainty. PMID- 2271577 TI - Phosphorescence and optically detected magnetic resonance studies of echinomycin DNA complexes. AB - Echinomycin complexes with polymeric DNAs and model duplex oligonucleotides have been studied by low-temperature phosphorescence and optical detection of triplet state magnetic resonance (ODMR) spectroscopy, with the quinoxaline chromophores of the drug used as intrinsic probes. Although not optically resolved, plots of ODMR transition frequencies versus monitored wavelength revealed heterogeneity in the phosphorescence emission of echinomycin, which was ascribed to the presence of two distinct quinoxaline triplet-state environments (referred to as the blue and red triplet states of echinomycin in this report). We think that a likely origin of the two triplet states of echinomycin is the occurrence of two or more distinct conformations of the drug in aqueous solutions. Spectroscopically observed perturbations of the triplet-state properties of echinomycin such as the phosphorescence emission spectrum, phosphorescence lifetime, ODMR spectrum, and zero-field splitting (zfs) energies were investigated upon drug binding to the double-stranded alternating copolymers poly(dG-dC).poly(dG-dC) [abbreviated as poly[d(G-C)2]] and poly(dA-dT).poly(dA-dT) [abbreviated as poly[d(A-T)2]], the homopolymer duplexes poly(dG).poly(dC) [abbreviated as poly(dG.dC)] and poly(dA).poly(dT) [abbreviated as poly(dA.dT)], and the natural DNAs from Escherichia coli, Micrococcus lysodeikticus, and calf thymus. Echinomycin bisintercalation complexes with the self-complementary oligonucleotides d(ACGT), d(CGTACG), and d(ACGTACGT), which are thought to model drug binding sites, were also investigated. Phosphorescence and ODMR spectroscopic results indicate that the quinoxaline chromophores of the drug are involved in aromatic stacking interactions in complexes with the natural DNAs as evidenced by red shifts in the phosphorescence 0,0 band of the drug, a small but significant reduction in the phosphorescence lifetime of the red triplet state, and reduction of the zfs D value of both the blue and red triplet states upon drug complexation. These changes in the triplet-state properties of echinomycin are consistent with stacking interactions that increase the polarizability of the quinoxaline environment. The extent of the reduction of the D parameter for the red triplet state upon complexation with the polymeric DNAs was found to correlate with the binding affinities measured for these targets [Wakelin, L. P. G., & Waring, M. J. (1976) Biochem. J. 157, 721-740], with the single exception of the drug-poly[d(G C)2] complex, for which an increase in the D-value was noted. In addition, upon drug binding to the natural DNAs, there is a reversal of signal polarity in the ODMR spectra of the red triplet state. Among the synthetic DNA polymers investigated, a reversal of ODMR signal polarity was found only with the echinomycin-poly[d(A-T)2] complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271578 TI - Purification and spectral study of a microbial fatty acyltransferase: activation by limited proteolysis. AB - A fatty acyltransferase with a reaction mechanism similar to that of mammalian lecithin: cholesterol acyltransferase has been purified from culture supernatants of a mutant Aeromonas salmonicida containing the cloned Aeromonas hydrophila structural gene. Typically, more than 35 mg of protein were isolated from 2 L of culture supernatant. The amino-terminal sequence, amino acid composition, and molecular weight of the purified protein corresponded to predictions based on the sequence of the gene, indicating that the signal sequence had been correctly removed during export but that no further processing had occurred. Analysis of the far-UV circular dichroic (CD) spectrum of the enzyme showed that it consists of 31% alpha-helix, 21% beta-sheet, and 16% beta-turn, with 12% of aperiodic form. Treatment of the purified protein with a variety of proteases resulted in nicking near the C-terminus. This led to an increase in enzyme activity against lipids in erythrocyte membranes and increased rate of hydrolysis of p-nitrophenyl butyrate. Activation was accompanied by a change in the CD spectrum and a change in its aggregation state. The trypsin cut site was located between the two cysteines in the enzyme. Evidence is presented that the cysteines are joined by a disulfide bond and therefore cannot participate in acyl transfer. This may distinguish the microbial enzyme from lecithin:cholesterol acyltransferase. This is the second extracellular A. hydrophila protein that we have shown can be activated by proteolysis after it is released. PMID- 2271579 TI - Maleimidobenzoyl-G-actin: structural properties and interaction with skeletal myosin subfragment-1. AB - We have investigated various structural and interaction properties of maleimidobenzoyl-G-actin (MBS-actin), a new, internally cross-linked G-actin derivative that does not exhibit, at moderate protein concentration, the salt- and myosin subfragment 1 (S-1)-induced polymerizations of G-actin and reacts reversibly and covalently in solution with S-1 at or near the F-actin binding region of the heavy chain (Bettache, N., Bertrand, R., & Kassab, R. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6028-6032). The far-ultraviolet CD spectrum and alpha helix content of the MBS-actin were identical with those displayed by native G actin. 45Ca2+ measurements showed the same content of tightly bound Ca2+ in MBS actin as in G-actin and the EDTA treatment of the modified protein promoted the same red shift of the intrinsic fluorescence spectrum as observed with native G actin. Incubation of concentrated MBS-actin solutions with 100 mM KCl + 5 mM MgCl2 led to the polymerization of the actin derivative when the critical monomer concentration reached 1.6 mg/mL, at 25 degrees C, pH 8.0. The MBS-F-actin formed activated the Mg2(+)-ATPase of S-1 to the same extent as native F-actin. The MBS G-actin exhibited a DNase I inhibitor activity very close to that found with native G-actin and was not to be at all affected by its specific covalent conjugation to S-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271580 TI - 51V NMR study of vanadate binding to myosin and its subfragment 1. AB - The binding of various forms of vanadate to myosin and myosin subfragment 1 (S-1) was studied by 51V NMR at increasing vanadate concentrations between 0.06 and 1.0 mM. The distribution of the various forms of vanadate in the solution depended on the total concentration of vanadate. At low concentrations, the predominant vanadate form was monomeric, while at high concentration, it was tetrameric. The presence of myosin or S-1 in the solution produced a significant broadening of the signal of each form of vanadate, indicating that all of them bind to the protein. Addition of ATP, which does not affect the 51V NMR spectra in the absence of proteins, causes their significant alteration in the presence of myosin or S-1. The changes, which include the broadening of the signal of the monomeric and the narrowing of the signal of the oligomeric vanadate forms, indicate that more monomeric and less oligomeric vanadate binds to the proteins in the presence than in the absence of ATP. Irradiation by near-UV light in the presence of vanadate cleaves S-1 at three specific sites--at 23, 31, and 74 kDa from the N-terminus. The cleavages at 23 and 31 kDa are specifically inhibited by the addition of ATP. The vanadate-associated photocleavage of S-1 also depends on the total concentration of vanadate; it is observed only when the concentration of vanadate is at least 0.2 mM. This was also the lowest concentration at which oligomeric vanadate was detected in the 51V NMR spectra. From the parallel concentration dependence of the photocleavage and the appearance of the tetrameric vanadate, it is concluded that photocleavage occurs only when tetrameric vanadate binds to S-1. PMID- 2271581 TI - A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man alpha 1 3Man beta 1-4GlcNAc. AB - A molecular mechanical force field is described for the conformational analysis of oligosaccharides. This force field has been derived by the addition of new parameters to the AMBER force field and is compatible with simulations of proteins. This new parametrization is assessed by comparison of the theoretically predicted conformations of Man alpha 1-3Man beta 1-4GlcNAc with the corresponding crystal structure. Molecular dynamics simulation data are presented for this structure both in vacuo and with the explicit inclusion of water molecules. While the former demonstrate significant torsional oscillations about glycosidic linkages at physiological temperature, in the latter these oscillations are highly damped due to the stabilizing influence of a "cage" of solvent-solvent and solvent-solute hydrogen bonds. PMID- 2271582 TI - Structures of the asparagine-linked sugar chain of glucose transporter from human erythrocytes. AB - The asparagine-linked sugar chain of glucose transporter from human erythrocytes was quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis. They were converted to radioactive oligosaccharides by NaB3H4 reduction after N-acetylation and fractionated by anion-exchange column chromatography and Bio-Gel P-4 column chromatography after sialidase treatment. Structural study of each oligosaccharide by exo- and endoglycosidase digestion and methylation analysis indicated that the glycoprotein contains a high-mannose type oligosaccharide, Man9.GlcNAc.GlcNAc, and biantennary complex-type oligosaccharides with Man alpha 1----6(+/- GlcNAc beta 1----4)(Man alpha 1----3) Man beta beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc as their cores and the poly-N-acetyllactosamine composed of about 16 N-acetyllactosaminyl units as their outer chains. These structural features of the sugar moiety of glucose transporter are quite different from those of two major intrinsic glycoproteins of human erythrocytes, glycophorin A and band 3. PMID- 2271583 TI - Interconversion of metarhodopsins I and II: a branched photointermediate decay model. AB - Flash photolysis experiments designed to monitor the establishment of the metarhodopsin I to metarhodopsin II equilibrium are interpreted according to a branched model in which two spectrally indistinguishable but kinetically distinguishable forms of metarhodopsin II are postulated to exist in equilibrium with a common pool of metarhodopsin I. This interpretation arises from the consistent requirement for at least three exponentials for a valid description of the observed growth of absorbance at 380 nm following bleaching of bovine rhodopsin in rod outer segment disk membranes. Analysis of the 380-nm transient absorbance data permitted direct determination of the five physically interpretable individual rate constants of the model. This analysis represents a more explicit interpretation of kinetic data than that employed in earlier experiments of this kind, which involved estimating only apparent rates and apparent amplitudes of discrete multiexponential functions. The 380-nm absorbance contributions of all relevant species contributing to the observed dynamic absorbance change were accounted for simultaneously during nonlinear least squares estimation of the model rate parameters. Analysis of deconvoluted equilibrium spectra acquired from samples identical with those used in the kinetics experiments confirmed the metarhodopsin I-metarhodopsin II equilibrium constants, Keq, derived from the dynamic analyses. It is shown that Keq varies from 1.28 at 10 degrees C to 7.3 at 37 degrees C and that approximately 90% of the metarhodopsin II present is in the form of metarhodopsin IIslow over the temperature range 10-37 degrees C. A physical interpretation of this decay model is discussed in the context of a distribution of metarhodopsin II structural and energetic states. PMID- 2271584 TI - Modulation of metarhodopsin formation by cholesterol-induced ordering of bilayer lipids. AB - The effect of lipid ordering on the kinetics and extent of metarhodopsin II (meta II) formation was evaluated in bovine rhodopsin which had been reconstituted into phosphatidylcholine vesicles containing 0, 15, and 30 mol% cholesterol. The rate of establishment of the dynamic equilibrium between metarhodopsin I (meta I) and the two kinetically distinguished forms of meta II in the branched meta II model [meta IIfast and meta IIslow; Straume, M., Mitchell, D. C., Miller, J. L., & Litman, B. J. (1990) Biochemistry (preceding paper in this issue)] is derived from kinetic measurements of rhodopsin photolysis in these vesicle systems at several temperatures. Values of the meta I in equilibrium with meta IItotal equilibrium constant, Keq, are calculated from the derived model-dependent rate constants, and are shown to be equivalent to those derived from rapidly acquired absorbance spectra. The presence of 30 mol% cholesterol reduces Keq by approximately 50% between 10 and 37 degrees C. Analysis of the model-dependent parameters in terms of delta H and delta S reveals that cholesterol raises the free energy of meta IIslow, relative to meta I, by increasing delta H whereas it raises the relative free energy of meta IIfast by making delta S meta IIfast relative to meta I less positive. The reduction in Keq by both temperature and cholesterol is found to be directly correlated with a parameter that reflects the free volume available for molecular motion in the hydrophobic core of the bilayer [Straume, M., & Litman, B. J. (1988) Biochemistry 27, 7723-7733].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271585 TI - Steady-state fluorescence and time-resolved fluorescence monitor changes in tryptophan environment in arginase from Saccharomyces cerevisiae upon removal of catalytic and structural metal ions. AB - Yeast arginase is a trimeric protein of identical subunits, each containing three tryptophans. Time-resolved fluorescence and steady-state fluorescence were employed to monitor the effects of removing the weakly bound catalytic Mn2+ as well as the tightly bound structural Zn2+/Mn2+. Resolution of the total native emission spectrum into decay-associated spectra (DAS) yielded components with lifetimes of 0.1, 1.2, and 4.0 ns. Upon removal of the catalytic metal, the intensities increased approximately 20% while the lifetimes increased less than 10%, and the DAS were unchanged except in intensity. The two major components are well resolved, but the 0.1-ns term is small and dominated by scattered excitation. In contrast, removal of the structural metal increased decay times to 0.2, 1.8, and 5.3 ns. More important, both native DAS red-shifted and became indistinguishable. These data suggest that removal of the catalytic metal does little to change the microenvironments of the individual tryptophans while removal of the structural metal causes partial unfolding of the protein. The excitation spectra for the active and inactive trimers were resolved into their excitation DAS (IEDAS), suggesting ground-state heterogeneity of the fluorescent species. In contrast, the excitation spectra of arginase without the structural metal could not be resolved due to the indistinguishable DAS. The tryptophans are quenched by acrylamide but not by cesium or iodide. Global analysis of the acrylamide quenching data resulted in two quenching decay-associated spectra (QDAS) which correlated well with the DAS. Since the apoenzyme does not exhibit tryptophan accessibility to either positive or negative ionic quenchers, one must assume that the "unfolded" monomeric protein retains considerable tertiary structure. PMID- 2271586 TI - Inhibition of thermolysin by phosphonamidate transition-state analogues: measurement of 31P-15N bond lengths and chemical shifts in two enzyme-inhibitor complexes by solid-state nuclear magnetic resonance. AB - 31P and 15N chemical shifts and 31P-15N bond lengths have been measured with solid-state NMR techniques in two inhibitors of thermolysin, carbobenzoxy-Glyp-L Leu-L-Ala (ZGpLA) and carbobenzoxy-L-Phep-L-Leu-L-Ala (ZFpLA), both as free lithium salts and when bound to the enzyme. Binding of both inhibitors to thermolysin results in large changes in the 31P chemical shifts. These changes are more dramatic for the tighter binding inhibitor ZFpLA, where a approximately 20 ppm downfield movement of the 31P isotropic chemical shift (sigma iso) is observed. This shift is due to changes in the shift tensor elements sigma 11 and sigma 22, while sigma 33 remains essentially constant. We observed a similar pattern for ZGpLA, but only a approximately 5 ppm change occurs in sigma iso. The changes in the 15N chemical shifts for both inhibitors are small upon binding, amounting to downfield shifts of 2 and 4 ppm for ZGpLA and ZFpLA, respectively. This indicates that there are no changes in the protonation state of the 15N in either the ZFpLA- or the ZGpLA-thermolysin complex. NMR distance measurements yield a P-N bond length rP-N = 1.68 +/- 0.03 A for the tight binding inhibitor ZFpLA both in its free lithium salt form and in its thermolysin-ZFpLA complex, a distance that is much shorter than the 1.90-A distance reported by X-ray crystallography studies [Holden et al. (1987) Biochemistry 26, 8542 8553].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271587 TI - Determination of protein secondary structure using factor analysis of infrared spectra. AB - A method is presented for determining the secondary structural composition of a protein in aqueous solution from its infrared spectrum. A factor analysis approach is used to analyze the infrared spectra of 18 proteins whose crystal structures are known from X-ray studies. Factor analysis followed by multiple linear regression identifies those eigenspectra that correlate with the variation in properties described by the calibration set. The properties of interest in this study are % alpha-helix, % beta-sheet, and % turns. In the analysis of an unknown, the factor loadings required to reproduce its spectrum are substituted in the regression equation for each property to predict its secondary structural composition. The accuracy of the method was determined by removing each standard, in turn, from the calibration set and using a calibration set generated from the remainder to predict its composition. By this method we obtain standard errors of prediction of 3.9% for alpha-helix, 8.3% for beta-sheet, and 6.6% for turns. The method may also be applied to the spectra of proteins in 2H2O. The method has important advantages over those currently in use for the quantitative analysis of the infrared spectra of proteins. Manipulation of the spectrum is kept to a minimum, no curve-fitting is necessary, and the several amide I band components need not be assigned. PMID- 2271588 TI - Subunit interactions in hemoglobin probed by fluorescence and high-pressure techniques. AB - The dissociation of the subunits of human adult oxyhemoglobin has been investigated by using steady-state fluorescence anisotropy, multifrequency phase fluorometry, and high hydrostatic pressure. Human hemoglobin obtained by using two purification procedures (bulk preparation by centrifugation or further fractionation using anion-exchange chromatography) was labeled with an extrinsic fluorescent probe, 5-(dimethylamino)naphthalene-1-sulfonyl chloride (DNS-Cl). The long fluorescence lifetime of this probe allows for the observation of the macromolecular tumbling, and thus provides a method for observing changes in the size of the complex upon subunit dissociation under differing solution conditions of proton and organic phosphate concentration. At pH 7, the dansylated preparations of bulk and fractionated hemoglobin showed a concentration-dependent decrease in the anisotropy which though not identical can only arise from the tetramer to dimer dissociation. We observed primarily the dimer at pH 9 and a small destabilization of the tetramer in the presence of saturating inositol hexaphosphate (IHP). High-pressure experiments allowed for the observation of the dissociation of the hemoglobin dimer into monomers. From these measurements, we estimate the dimer dissociation constant to be between 0.1 and 1 nM. We compare the present results on the subunit affinities in hemoglobin obtained from steady state and time-resolved fluorescence data with those obtained previously by using gel filtration, sedimentation, and kinetic techniques. These comparisons are indicative of a certain degree of conformational heterogeneity in the hemoglobin preparations. PMID- 2271589 TI - Synthetic peptide model of an essential region of an aminoacyl-tRNA synthetase. AB - A 40 amino acid sequence of the unsolved structure of Escherichia coli alanine tRNA synthetase is essential for tRNA binding and encodes an immunological determinant that cross-reacts with antibodies raised against a eukaryote (insect Bombyx mori) alanine enzyme. The secondary structure of this sequence is predicted to be an amphiphilic alpha-helix that includes one aspartyl and eight glutamyl side chain carboxyl groups. The antibody reactivity and the conformation of a synthetic peptide model of this region (Glu346 to Ser385) were investigated. In addition, double Arg----Gln and Leu----Ala substitutions were separately placed in the enzyme on the hydrophilic and hydrophobic face, respectively, of the predicted helix. These mutations conserve the polar/nonpolar character of each face and retain the potential for helix formation. Circular dichroism spectra of the synthetic peptide model demonstrate the potential for amphiphilic helix formation for the segment from Glu346 to Ser385. The behavior of the mutations in the enzyme, together with earlier data and immunological assays presented here, suggests that one face of the putative helix is an antigenic region of the surface of the enzyme where it contributes to the interaction with alanine tRNA and that the specific sequence of the helix is an important determinant of enzyme stability. PMID- 2271590 TI - Cadmium-113 NMR studies of the DNA binding domain of the mammalian glucocorticoid receptor. AB - The DNA binding domain of the mammalian glucocorticoid hormone receptor (GR) contains nine highly conserved cysteine residues, a conservation shared by the superfamily of steroid and thyroid hormone receptors. A fragment [150 amino acids (AA) in length] consisting of GR residues 407-556, containing within it the entire DNA binding domain (residues 440-525), has been overexpressed and purified from Escherichia coli previously. This fragment has been shown to contain 2.3 +/- 0.2 mol of Zn(II) per mole of protein [Freedman, L. P., Luisi, B. F., Korszun, Z. R., Basavappa, R., Sigler, P. B., & Yamamoto, K. R. (1988) Nature 334, 543]. Zn(II) [or Cd(II) substitution] has been shown to be essential for specific DNA binding. 113Cd NMR of a cloned construct containing the minimal DNA binding domain of 86 AA residues [denoted GR(440-525)] with 113Cd(II) substituted for Zn(II) identifies 2 Cd(II) binding sites by the presence of 2 113Cd NMR signals each of which integrates to 1 113Cd nucleus. The chemical shifts of these two sites, 704 and 710 ppm, suggest that each 113Cd(II) is coordinated to four isolated -S- ligands. Shared -S- ligands connecting the two 113Cd(II) ions do not appear to be present, since their T1s differ by 10-fold, 0.2 and 2.0 s, respectively. Addition of a third 113Cd(II) or Zn(II) to 113Cd2GR(440-525) results in occupancy of a third site, which introduces exchange modulation of the two original 113Cd NMR signals causing them to disappear. Addition of EDTA to the protein restores the original two signals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271591 TI - Interaction of oligonucleotides containing 6-O-methylguanine with human DNA (cytosine-5-)-methyltransferase [published erratumm appears in Biochemistry 1992 Aug 4;31(30):7008]. AB - Thirty-base-pair synthetic oligonucleotide duplexes containing a single meG.C (meG = 6-O-methylguanine) or A.C base pair at the 16th position (i.e., 5' CCCGTTTAAATATACXTATACCCGGGTACC-3', where X = A or meG) were used to study de novo methylation by the purified human DNA (cytosine-5)-methyltransferase isolated from CEM cells. Both duplexes containing meG.C and A.C base pairs show enhanced methyl group acceptor properties. Subsequent introduction of hemimethylated sites at the 15th position of the top strand (the C residue next to the abnormal base pair) and the 7th, 15th (which represents the C residue in the 6meG.C and A.C base pairs), and 27th positions of the bottom strand were used to study the maintenance methylation of the hemimethylated duplexes by the methylase. This revealed striking differences in the rate, amount, and sites of methylation, which are dependent on the position of the hemimethylated site in the duplex. The possible mechanism of action of the methylase is discussed. The data show that 6 O-methylguanine residues in DNA can have other genetic effects apart from their miscoding behavior and that meG.C and A.C base pairs exert different effects in terms of methylation. PMID- 2271592 TI - Role of the Cro repressor carboxy-terminal domain and flexible dimer linkage in operator and nonspecific DNA binding. AB - A series of mutations comprising single and multiple substitutions, deletions, and extensions within the carboxy-terminal domain of the bacteriophage lambda Cro repressor have been constructed. These mutations generally affect the affinity of repressor for specific and nonspecific DNA. Additionally, substitution of the carboxy-terminal alanine with several amino acids capable of hydrogen-bonding interactions leads to improved specific binding affinities. A mutation is also described whereby cysteine links the two Cro monomers by a disulfide bond. As a consequence, a significant improvement in nonspecific binding and a concomitant reduction in specific binding are observed with this mutant. These results provide evidence that the carboxy terminus of Cro repressor is an important DNA binding domain and that a flexible connection between the two repressor monomers is a critical factor in modulating the affinity of wild-type repressor for DNA. PMID- 2271593 TI - Analysis of fluorescence energy transfer in duplex and branched DNA molecules. AB - Nonradiative fluorescence energy transfer (FET) is thought to be a highly sensitive measure of distance, occurring through a dipole coupling (Forster) mechanism in which the efficiency of FET depends on the inverse sixth power of the distance between fluorophores. The current work assesses the utility of FET for measuring distances in duplex and branched DNA molecules. The apparent efficiencies of FET between donor (fluorescein) and acceptor (eosin) fluorophores attached to opposite ends of oligonucleotide duplexes of varying length were determined; the results suggest that FET is a useful qualitative indicator of distance in DNA molecules. However, the apparent FET efficiency values cannot be fit to the Forster equation without the specification of highly extended DNA-to fluorophore tethers and motionally restricted fluorophores, conditions that are unlikely to coexist. Three other lines of evidence further suggest that factors in addition to Forster transfer contribute to apparent FET in DNA: (1) The efficiency of FET appears to depend on the base sequence in some instances. (2) Donor fluorescence changes with the extent of thermally induced DNA melting in a sequence-dependent fashion, indicating dye-DNA interactions. (3) The distances between the ends of various pairwise combinations of arms of a DNA four-way junction do not vary as much as expected from previous work. Thus, the occurrence of any nondipolar effects on energy transfer in oligonucleotide systems must be defined before distances in DNA molecules can be quantified by using FET. PMID- 2271594 TI - Validity of the nearest-neighbor approximation in the evaluation of the electrophoretic manifestations of DNA curvature. AB - The validity of a theoretical nearest-neighbor model based on conformational energy calculations, for translating the deterministic fluctuations of DNA base sequences in superstructural elements, is tested on the electrophoretic data of 450 multimeric, duplex oligonucleotides with different sequence, periodicity, and complexity, corresponding to all the experimental data so far published. An accurate semiempirical linear relation between the gel electrophoretic retardation and the dispersion of the theoretical curvature was found which allows a prediction of electrophoretic anomalies of DNA tracts, e.g., the cyclic permutation gel assays, with great confidence. Such a pattern of agreement allows the interpretation of the gel electrophoresis retardation as due to an increase of activation energy required in straightening the DNA axis. PMID- 2271595 TI - Construction and expression of a novel recombinant anaphylatoxin, C5a-N19, as a probe for the human C5a receptor. AB - We have constructed a novel recombinant C5a anaphylatoxin (C5a-N19) containing a 19-residue amino-terminal extension peptide, using a plasmid vector which secretes the nascent polypeptide to the Escherichia coli periplasmic space. C5a N19 was purified from cell lysates by immunoaffinity chromatography using a monoclonal antibody which recognizes a portion of the amino-terminal extension peptide. C5a-N19 was characterized as biologically indistinguishable from the unmodified recombinant anaphylatoxin for release of lysosomal enzymes from dibutyryl-cAMP-differentiated U937 cells. In contrast to unmodified C5a, which is not recognized by anti-C5a antibodies following binding to its cellular receptor, receptor-bound C5a-N19 is recognized by the monoclonal antibody directed against the amino-terminal extension sequence. Because the monoclonal antibody recognizes the C5a-receptor complex on cells, this methodology is useful in fluorescence sorting of C5a receptor-positive cells. A C5a receptor affinity column was constructed by saturating monoclonal antibody bound to agarose with C5a-N19. Digitonin-solubilized C5a receptor from dibutyryl-cAMP-induced U937 cells was adsorbed to the matrix and eluted by dissociation of the ligand-receptor complex from the antibody. Analysis by SDS-polyacrylamide gel electrophoresis revealed a unique protein band at 41K, consistent with the molecular weight predicted from cross-linking experiments when the contribution of C5a is subtracted. Development of this recombinant C5a derivative provides a useful probe previously unavailable for the C5a receptor molecule. PMID- 2271596 TI - Equilibrium denaturation of insulin and proinsulin. AB - The guanidine hydrochloride induced equilibrium denaturation of insulin and proinsulin was studied by using near- and far-ultraviolet (UV) circular dichroism (CD). The denaturation transition of insulin is reversible, cooperative, symmetrical, and the same whether detected by near- or far-UV CD. These results are consistent with a two-state denaturation process without any appreciable equilibrium intermediates. Analysis of the insulin denaturation data yields a Gibbs free energy of unfolding of 4.5 +/- 0.5 kcal/mol. Denaturation of proinsulin detected by near-UV CD appears to be the same as for insulin, but if detected by far-UV CD appears different. The far-UV CD results demonstrate a multiphasic transition with the connecting peptide portion unfolding at lower concentrations of denaturant. Similar studies with the isolated C-peptide show that its conformation and susceptibility to denaturation are independent of the rest of the proinsulin molecule. After the proinsulin denaturation results were adjusted for the connecting peptide contribution, a denaturation transition identical with that of insulin was obtained. These results show that for proinsulin, the connecting peptide segment is not a random coil; it is an autonomous folding unit, and the portion corresponding to insulin is identical with insulin in terms of conformational stability. PMID- 2271597 TI - Hazards and their exploitation in the applications of molecular biology to structure-function relationships. PMID- 2271598 TI - Determination of the major tautomeric form of the covalently modified adenine in the (+)-CC-1065-DNA adduct by 1H and 15N NMR studies. AB - (+)-CC-1065 is an extremely potent antitumor antibiotic produced by Streptomyces zelensis. The potent cytotoxic effects of the drug are thought to be due to the formation of a covalent adduct with DNA through N3 of adenine. Although the covalent linkage sites between (+)-CC-1065 and DNA have been determined, the tautomeric form of the covalently modified adenine in the (+)-CC-1065-DNA duplex adduct was not defined. A [6-15N]deoxyadenosine-labeled 12 base pair non-self complementary oligomer, d(GGCGGAGTT*AGG).d(CCTAACTCCGCC) (asterisk indicates 15N labeled base), containing the (+)-CC-1065 most preferred binding sequence 5'AGTTA, was synthesized and modified with (+)-CC-1065. This [6 15N]deoxyadenosine-labeled 12-mer duplex adduct was then studied by 1H and 15N NMR. One-dimensional NOE difference and two-dimensional NOESY 1H NMR experiments on the nonisotopically labeled 12-mer duplex adduct demonstrate that the 6-amino protons of the covalently modified adenine exhibit two signals at 9.19 and 9.08 ppm. Proton NMR experiments on the [6-15N]deoxyadenosine-labeled 12-mer duplex adduct show that the two resonance signals for adenine H6 observed on the nonisotopically labeled duplex adduct were split into doublets by the 15N nucleus with coupling constants of 91.3 Hz for non-hydrogen-bonded and 86.8 Hz for hydrogen-bonded amino protons. Parallel 15N NMR experiments on the [6 15N]deoxyadenosine-labeled (+)-CC-1065-12-mer duplex adduct show a triplet-like signal around -276.9 ppm and coupling constants of 91.5 and 85.6 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271599 TI - Comparison of chemical reactivity, cytotoxicity, interstrand cross-linking and DNA sequence specificity of bis(platinum) complexes containing monodentate or bidentate coordination spheres with their monomeric analogues. AB - The properties of a new bis(platinum) complex containing two monodentate coordination spheres, [(trans-PtCl(NH3)2)2H2N(CH2)4NH2]Cl2 (1,1/t,t), are reported. Comparison is made with respect to chemical reactivity, in vitro biological activity in murine and tumor cells, DNA conformational changes, cross linking efficiency, and sequence specificity between this complex and the previously reported complex containing two bidentate platinum atoms, [(Pt(mal)(NH3))2H2N(CH2)4NH2] (2,2/c,c), as well as with their respective monomeric analogues, [PtCl(dien)]Cl and cis-[PtCl2(NH3)2](cis-DDP). While both bis(platinum) complexes are active against cis-DDP-resistant cells, the monodentate bis(platinum) complex (1,1/t,t) has a lower resistance factor than the complex with bidentate coordination spheres (2,2/c,c). More importantly, this property is repeated in a human ovarian carcinoma cell line. DNA-binding studies show that DNA interstrand cross-linking is more efficient for the 1,1/t,t complex. DNA sequencing studies employing the exonuclease activity of T4 polymerase demonstrate that there are a variety of binding sites; some are common to all complexes and some common to both bis(platinum) complexes, while the monodentate 1,1/t,t species also reacts at unique sites, not attacked by any of the other complexes studied. The circular dichroism of CT DNA modified by the 1,1/t,t complex is also unique and is not seen for any of the other agents. PMID- 2271600 TI - Investigation of the inhibitory role of phosphorothioate internucleotidic linkages on the catalytic activity of the restriction endonuclease EcoRV. AB - The inhibitory effect of phosphorothioate residues, located within one strand of double-stranded DNA, on the hydrolytic activity of the restriction endonuclease EcoRV was investigated. Specific incorporation of a phosphorothioate group at the site of cleavage yielded the sequence 5'-GATsATC-3'. This modified sequence was cleaved at a relative rate of 0.1 compared to the unmodified substrate. Substrates 5'-GATsAsTC-3' and 5'-GsATsATC-3', both containing one additional phosphorothioate substitution, were linearized at a rate of 0.04 relative to unmodified DNA. However, under the same conditions, fully dAMPS-substituted DNA was found to be virtually resistant to the hydrolytic activity of EcoRV. Further experiments showed that double-stranded DNA fragments generated by PCR containing phosphorothioate groups within both strands are potent inhibitors of EcoRV catalysis. The inhibition was independent of whether the inhibitor fragment contained an EcoRV recognition site. We concluded that substitution of the phosphate group at the site of cleavage by a phosphorothioate residue decreases the rate of EcoRV-catalyzed hydrolysis most significantly. Substitution of other phosphate groups within the recognition sequence plays a limited role in enzyme inhibition. The presence of multiple dNMPS residues at regions of the DNA removed from the EcoRV recognition site may decrease the amount of enzyme available for catalysis by nonspecific binding to EcoRV. PMID- 2271601 TI - Properties of bacteriophage T4 thymidylate synthase following mutagenic changes in the active site and folate binding region. AB - Amino acid replacements have been introduced in specific sites of bacteriophage T4 thymidylate synthase (T4-TS) to assess the role that these changes have on enzyme activity. Each of the conserved amino acids in the active-site region of T4-TS was modified, and the effects that these changes had on the kinetic and physical properties of this enzyme were measured. The mutations introduced were Pro-155-Ala (P155A), Cys-156-Ser (C156S), and His-157-Val (H157V) with the resulting synthases possessing kcat's of 10.3, 0.008, and 2.70 s-1, respectively, relative to that of the wild-type enzyme of 11.8 s-1. Equilibrium dialysis was performed on the wild-type and mutant enzymes to determine the binding constants for 2'-deoxyuridylate and 5-fluoro-2'-deoxyuridylate, and while in most cases the extent of binding of these nucleotides to the mutant proteins was reduced when compared with wild-type TS, the number of binding sites involved remained about 1 or less for the binary complex and almost 2 for the ternary complex. Heat and urea stability studies revealed that the mutant with the highest enzyme activity, P155A, was the most unstable, while spectrofluorometric analyses revealed that the structures of P155A and H157V were perturbed relative to the C156S and wild type TSs. These studies are in agreement with others implicating the phylogenetically conserved active-site cysteine as playing an essential mechanistic role in the catalytic process promoted by TS. The proximal amino acids on either side of this cysteine, although also highly conserved, do not appear to affect the catalytic mechanism directly, but may do so indirectly through their influence on the conformation at the active site as well as other regions of the enzyme. Amino acids replacements were introduced also into the folate and deoxynucleotide 5'-phosphate binding sites of the T4-phage TS to ascertain the potential role that these amino acids play in the catalytic process. These positions were selected on the basis of previous chemical modification and X-ray crystallographic studies on Lactobacillus casei TS. Amino acid residues 48 and 49, which are in the putative folate binding site, were converted from lysines to arginines; in the former case, the mutated enzyme had less than 7% of the wild-type activity while in the latter, the mutated enzyme still retained about 60% of its activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271602 TI - Replacement of a labile aspartyl residue increases the stability of human epidermal growth factor. AB - Long-term storage of recombinant human epidermal growth factor (EGF), an important promoter of cell division, results in its conversion to a new species that elutes later than native EGF on a reverse-phase column. This new species, called EGF-X, has only 20% of the biological activity of native EGF. Peptide mapping indicated that the primary structure of EGF-X differs from that of native EGF solely within the first 13 residues. N-Terminal sequencing of EGF-X revealed that about 30% of the polypeptides have been cleaved at the Asp-3/Ser-4 bond. In addition, the yields after the His residue at position 10 were extremely low, indicating that a chemical modification occurs at residue 11 that is incompatible with Edman degradation. We hypothesized that aspartic acid 11 had been converted to an isoaspartyl residue, and this was confirmed with L-isoaspartyl/D-aspartyl methyltransferase, an enzyme that methylates the side-chain carboxyl group of L isoaspartyl residues but does not recognize normal L-aspartyl residues. EGF-X, but not EGF, was found to be a substrate of this enzyme, and proteolytic digestion of EGF-X with thermolysin localized the site of methylation to a nine residue peptide containing position 11. We did not observe formation of the isoaspartyl derivative in EGF that had been denatured by reduction of its disulfide bonds. In addition, replacement of the aspartyl residue at position 11 with glutamic acid resulted in a fully active EGF derivative that does not form detectable amounts of EGF-X. We propose that conversion of this aspartyl residue to isoaspartate is a significant nonenzymatic degradation reaction affecting this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271603 TI - Folding of a predominantly beta-structure protein: rat intestinal fatty acid binding protein. AB - The equilibrium and kinetic properties of the unfolding-refolding transitions of Escherichia coli derived rat intestinal fatty acid binding protein have been examined using several different denaturants. This protein, which contains 2 tryptophans but no prolines or cysteines, has a predominantly beta-structure: its 10 antiparallel beta-strands are organized into 2 orthogonal sheets surrounding a large solvent-filled internal cavity. For urea and guanidine hydrochloride, the completely reversible transition was monitored by circular dichroism, absorbance, and fluorescence spectroscopy. Each of these data sets was best fit by a simple, two-state model involving only native and unfolded forms. However, linear extrapolation to determine the free energy of folding in the absence of denaturant resulted in different values for the free energy of folding depending upon which denaturant was used. When fluorescence was used to monitor the transition, the extrapolated free energy estimates for the two denaturants were markedly different: 10.03 +/- 0.24 kcal mol-1 for urea versus 5.22 +/- 0.33 kcal mol-1 for guanidine hydrochloride. The midpoints of these transitions were 5.51 and 1.36 M, respectively. The transition caused by either denaturant as monitored by circular dichroism and absorbance spectroscopy was virtually coincident with that monitored by fluorescence, further supporting the assignment of a two-state model for the equilibrium results. The addition of a 2-fold molar excess of ligand (oleate) increased the extrapolated estimates approximately 2.5 kcal mol-1 for both denaturants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271604 TI - A solid-state deuterium NMR investigation of conformation and order in magnetically oriented [d(CGCGAATTCGCG)]2. AB - Solid-state deuterium NMR has been used to investigate the oriented liquid crystal phase of the hydrated oligonucleotide [d(CGCGAATTCGCG)]2. Previous investigations have shown that the helix axis is aligned perpendicular to the magnetic field, while at reduced temperatures motion about the helix axis is eliminated. Synthetic oligonucleotide samples incorporating different labeled nucleosides, [2"-2H]-2'-deoxyadenosine, [methyl-2H]thymidine, [8-2H]-2' deoxyguanosine, and [8-2H]-2'-deoxyadenosine, permitted investigation of both the base and sugar conformation and ordering in the aligned phase. From line-shape analysis of the purine-labeled samples the orientation of the base C8 C-D bond with respect to the helix axis was determined to be theta = 90 degrees with a distribution of sigma total = 20 degrees, which is comparable to the orientation of theta = 90 degrees, sigma total = 15 degrees, with an oriented fraction P = 0.7 found for the C3 symmetry axis of the methyl-labeled dodecamer. The orientation of the sugar 2" C-D bond with respect to the helix axis is theta = 22 degrees with a distribution of sigma total = 15 degrees in agreement with the expected C2'-endo sugar conformation. The fraction of C3'-endo was also investigated and from analysis of line shape cannot exceed 20%. These results, though preliminary in nature, illustrate the application of this aligned phase for structural investigations. PMID- 2271605 TI - 1H NMR study of the influence of hydrophobic contacts on protein-prosthetic group recognition in bovine and rat ferricytochrome b5. AB - The proton nuclear magnetic resonance spectra of the soluble fragment of native bovine and genetically engineered wild-type rat ferricytochrome b5 reconstituted with a wide variety of hemes chemically modified at 2- and/or 4-positions have been recorded and analyzed. While all but one nonsymmetric heme yielded comparable amounts of the two heme orientations immediately after reconstitution, the relative proportion of the two orientations at equilibrium varied widely. The unpaired spin density distribution in the heme pi system leads to substituent hyperfine shift patterns in these paramagnetic complexes that are completely diagnostic of the heme orientation in the protein matrix. An empirical assignment strategy is outlined and applied which allows unequivocal assignment of the absolute orientation of a derivatized heme within the protein matrix. Using a series of hemes lacking 2-fold symmetry solely due to a single substitution, the preferences for localized site occupation of vinyls, methyls, and hydrogens are developed. The large differences in relative stability of the two orientations of native protohemin in the two cytochromes b5 is shown to result from the additivity of localized effects for the bovine protein and the near cancellation of competing effects in the rat protein. The major determinant of the heme orientation is judged to be a repulsive interaction between a vinyl and a hydrophobic cluster of amino acids including positions 23 and 25. The differences in this heme orientational preference among bovine, rat, and chicken ferricytochromes b5 could be correlated with the relative steric bulk of the residues at positions 23 and 25.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271606 TI - Quenching of tryptophan fluorescence by brominated phospholipid. AB - Bromolipids [1-palmitoyl-2-(dibromostearoyl)phosphatidylcholine] with bromines at the 4,5-, 6,7-, 9,10-, 11,12-, and 15,16-positions were used to examine the fluorescence quenching of a synthetic, membrane-spanning peptide (Lys2-Gly-Leu8 Trp-Leu8-Lys-Ala-amide) incorporated into both small and large unilamellar vesicles. The peptide-lipid vesicles were analyzed to show that at least 75% of the peptide was in a transbilayer configuration, placing the single tryptophan in its predicted place in the center of the bilayer. Quenching profiles of the peptide in bromolipid showed maximal (90%) quenching by the 15,16-bromolipid, indicating that the bromolipids can accurately locate the position of a tryptophan in the bilayer. The quenching by the other bromolipids decreased with an r6 dependence and an apparent R0 of 9 A. In addition, indole in methanolic solution was subjected to quenching by a variety of mono- and dibrominated hydrocarbons. The quenching was analyzed, by using a modified Stern-Volmer equation, and found to be greatly dependent upon the number and positioning of the bromines. Monobromobutanes were found to have a quenching efficiency of only 7% while dibromobutanes, with bromines on adjacent carbon atoms, had efficiencies of over 80%. In addition, the dibromobutanes exhibited significant "static" quenching whereas the monobrominated butanes did not. These data suggest that the bromolipids are more appropriately defined as short-range quenchers rather than strictly contact quenchers. PMID- 2271607 TI - Evidence for an S-farnesylcysteine methyl ester at the carboxyl terminus of the Saccharomyces cerevisiae RAS2 protein. AB - The protein products of yeast and mammalian ras genes are posttranslationally modified to give mature forms that are localized to the inner surface of the plasma membrane. We have previously demonstrated that the mature form of the Saccharomyces cerevisiae RAS2 gene product is methyl esterified at a modified C terminal cysteine residue. Here we provide evidence that this residue is an S farnesylcysteine alpha-carboxyl methyl ester. This result establishes common posttranslational modifications for RAS proteins and fungal sex factors. These polypeptides exhibit sequence similarities at their C-termini that appear to be the critical recognition elements for a common set of modification enzymes. In mammalian cells, proteins with analogous C-terminal sequences appear to be prenylated and carboxyl methylated by a similar mechanism. PMID- 2271608 TI - Partial 1H NMR assignments of the Escherichia coli dihydrofolate reductase complex with folate: evidence for a unique conformation of bound folate. AB - Sequence-specific 1H assignments have been made for over 25% of the amino acid side chains of Escherichia coli dihydrofolate reductase complexed with folate by using a variety of two-dimensional techniques. Proton resonances were assigned by using a combination of site-directed mutagenesis and a knowledge of the X-ray crystal structure. Unique sets of NOE connectivities present in hydrophobic pockets were matched with the X-ray structure and used to assign many of the residues. Other residues, particularly those near or in the active site, were assigned by site-directed mutagenesis. The ability to assign unambiguously the proton resonances of these catalytically important residues allowed for extensive networks of NOE connectivities to follow from these assignments. As a consequence of these assignments, the orientation of the pterin ring of folate could be determined, and its conformation is similar to that of the productive dihydrofolate complex. Under these experimental conditions, only one bound form of the pterin ring could be detected. PMID- 2271609 TI - Substrate specificities and mechanism in the enzymatic processing of vitamin A into 11-cis-retinol. AB - The biosynthesis of 11-cis-retinol in the retinal pigment epithelium requires two consecutive enzymatic reactions. The first involves the esterification of all trans-retinol by lecithin retinol acyltransferase (LRAT). The second reaction involves the direct conversion of an all-trans-retinyl ester into 11-cis-retinol by an isomerase-like enzyme. This latter reaction couples the free energy of hydrolysis of an ester to the thermodynamically uphill trans to cis conversion, thus providing the energy to drive the latter process. In this paper both enzymes are studied with respect to their substrate specificities to provide information on mechanism. The isomerase is shown to be highly specific with respect to the ionylidene ring system and substitution at C15, whereas sterically bulkier substituents at C9 and C11 are permitted. C5 and C13 demethyl retinoids are isomerized, removing from consideration isomerization mechanisms involving C-H abstraction at the C5 or C13 methyl groups of the retinoid. On the other hand, C9 demethyl retinoids are not isomerized. A C-H abstraction mechanism is unlikely at the C9 methyl group as well, because no kinetic deuterium isotope effect is found with all-trans-19,19,19-trideuterioretinoids and isomerization of unlabeled retinoids occurs without the incorporation of deuterium when the isomerization is performed in D2O. LRAT proved to be broadly specific for retinols but was relatively inert with other hydrophobic alcohols including cholesterol. The enzyme is also highly specific for phosphatidylcholine analogues versus other potential membranous acyl donors such as phosphatidylethanolamine and phosphatidylserine. PMID- 2271610 TI - Fusion of influenza hemagglutinin-expressing fibroblasts with glycophorin-bearing liposomes: role of hemagglutinin surface density. AB - Influenza virus gains access to the cytoplasm of its host cell by means of a fusion event between viral and host cell membrane. Fusion is mediated by the envelope glycoprotein hemagglutinin (HA) and is triggered by low pH. To learn how many hemagglutinin trimers are necessary to cause membrane fusion, we have used two NIH 3T3 fibroblast cell lines that express HA protein at different surface densities. On the basis of quantitations of the number of HA trimers per cell and the relative surface areas of the two cell lines, the HAb-2 cells have a 1.9-fold higher plasma membrane surface density than the GP4F cells. The membrane lateral diffusion coefficient and the mobile fraction for HA is the same for both cell lines. A Scatchard analysis of the binding of glycophorin-bearing liposomes to the cells showed 1700 binding sites for the GP4F cells and 3750 binding sites for the HAb-2 cells, with effectively the same liposome-cell binding constant, about 7 x 10(10) M-1. Binding was specific for glycophorin on the liposomes and HA expressed on the cells. A competition experiment employing toxin-containing and empty liposomes allowed us to quantitate the number of liposomes that fused per cell, which was a small constant fraction of the number of bound liposomes. For the HAb-2 cells, about 1 in every 70 bound liposomes fused and for the GP4F cells about 1 in every 300 bound liposomes fused. Hence, the HAb-2 cells showed 4.4 times more fusion per bound liposome, even though the surface density of HA was only 1.9 times greater. We conclude the following: (i) One HA trimer is not sufficient to induce fusion. (ii) The HA bound to glycophorin is not the HA that induces fusion. That is, even though each HA has a binding and a fusion function, those functions are not performed by the same HA trimer. PMID- 2271611 TI - Kinetics of nucleotide transport in rat heart mitochondria studied by a rapid filtration technique. AB - A rapid filtration technique has been used to measure at room temperature the kinetics of ADP and ATP transport in rat heart mitochondria in the millisecond time range. Transport was stopped by cessation of the nucleotide supply, without the use of a transport inhibitor, thus avoiding any quenching delay. The mitochondria were preincubated for 30 s either in isotonic KCl containing succinate, MgCl2, and Pi (medium P) or in isotonic KCl supplemented only with EDTA and Tris (medium K); they were referred to as energized and resting mitochondria, respectively. The kinetics of [14C]ADP transport in energized mitochondria were apparently monophasic. The plateau value for [14C]ADP uptake reached 4-5 nmol of nucleotide.(mg of protein)-1. Vmax values for [14C]ADP transport of 400-450 nmol exchanged.min-1.(mg of protein)-1 with Km values of the order of 13-15 microM were calculated, consistent with rates of phosphorylation in the presence of succinate of 320-400 nmol of ATP formed.min-1.(mg of protein) 1. The rate of transport of [14C]ATP in energized mitochondria was 5-10 times lower than that of [14C]ADP. Upon uncoupling, the rate of [14C]ATP uptake was enhanced, and that of [14C]ADP uptake was decreased. However, the two rates did not equalize, indicating that transport was not exclusively electrogenic. Transport of [14C]ADP and [14C]ATP by resting mitochondria followed biphasic kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271612 TI - Ribosomal protein L35: identification in spinach chloroplasts and isolation of a cDNA clone encoding its cytoplasmic precursor. AB - We describe the isolation of spinach chloroplast ribosomal protein L35 and characterization of a cDNA clone encoding its cytoplasmic precursor. This protein was only recently identified in ribosomes, but the sequences of four L35 genes have now been reported and confirm its presence in eubacteria, chloroplasts, and cyanelles. Using N-terminal sequence data, oligonucleotides were designed and a cDNA library was screened. The nucleotide sequence of the cDNA clones shows that the spinach L35 protein is encoded as a precursor of 159 residues, comprising a mature protein of 73 residues and a transit peptide of 86 residues. The cleavage site for forming the mature protein is deduced to be Thr-Val-Phe-Ala decreases Ala-Lys-Gly-Tyr. The L35 protein in the photosynthetic organelle of the protozoan Cyanophora paradoxa is encoded in the organelle DNA [Bryant & Stirewalt (1990) FEBS Lett. 259, 273-280]. The corresponding gene has not been found in the chloroplast DNA of a lower plant (liverwort) and two higher plants. Our results demonstrate that the L35 protein in a higher plant (spinach) is encoded in the nucleus. This finding, in light of the endosymbiont hypothesis, suggests an organelle to nucleus transfer of the L35 gene at the evolutionary beginnings of land plants. PMID- 2271613 TI - Substrates of cGMP kinase in vascular smooth muscle and their role in the relaxation process. AB - G1 is a hitherto unidentified substrate (molecular mass about 120 kDa) of the cGMP-dependent kinase, although its presence in vascular smooth muscle sarcolemma has been known for many years. Since it represents the major target of the G kinase in smooth muscle, its physicochemical and biochemical properties were investigated. Solubilization of G1 required a detergent: with Triton X-100, however, its extraction only occurred in the presence of high salt concentrations or millimolar ATP. These properties are typical for a membrane protein interacting with a nonmembraneous sedimentable moiety. Cupric phenanthroline catalyzed oxidation revealed that the G1 phosphoprotein could be oxidatively cross-linked to a sedimentable moiety. The latter was identified by two dimensional (nonreduced/reduced) gel electrophoresis as actin which is attached to the sarcolemma. Furthermore, DNase I affinity chromatography demonstrated an interaction of solubilized G1 with actin. The results suggest a role of G1 in the plasma membrane-cytoskeleton interaction in smooth muscle cells. PMID- 2271614 TI - Single-strand DNA triple-helix formation. AB - Chemical modification studies provide evidence that single-stranded oligodeoxyribonucleotides can form stable intrastrand triple helices. Two oligonucleotides of opposite polarity were synthesized, each composed of a homopurine-homopyrimidine hairpin stem linked to a pyrimidine sequence which is capable of folding back on the hairpin stem and forming specific Hoogsteen hydrogen bonds. Using potassium permanganate as a chemical modification reagent, we have found that two oligodeoxyribonucleotides of sequence composition type 5' (purine)8(N)4(pyrimidine)8(N)6(pyrimidine)8-3' and 5' (pyrimidine)8N6(pyrimidine)8N4(purine)8-3' undergo dramatic structural changes consistent with intrastrand DNA triple-helix formation induced by lowering the pH or raising the Mg2+ concentration. The intrastrand DNA triple helix is sensitive to base mismatches. PMID- 2271615 TI - Direct and indirect pathways of functional coupling in human hemoglobin are revealed by quantitative low-temperature isoelectric focusing of mutant hybrids. AB - Functional energetic coupling within human hemoglobin has been explored by using quantitative analysis of asymmetric mutant hybrid equilibria. Previous work showed that the free energy of cooperativity is largely attributable to alterations in free energy that accompany changing interactions at the interface between alpha 1 beta 1 and alpha 2 beta 2 dimers [Pettigrew et al. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 1849]. However, the issue of how cooperativity-linked sites in the molecule are energetically coupled in manifesting cooperative ligation is still not well delineated. In this paper we address the questions of what types of functional coupling pathways are operational in hemoglobin, what some of their characteristics are, and how they are related to one another. By constructing asymmetric mutant hybrid hemoglobins, we can assay how two structurally identical, symmetrically equivalent sites are energetically coupled in manifesting subunit assembly and/or cooperative ligation. Asymmetric hybrid hemoglobins, i.e., those containing a single modified site, cannot be isolated and must be studied in equilibrium with their symmetric parent molecules. In order to study these asymmetric hybrid equilibria, we have developed new theory and quantitation techniques to augment the low-temperature quenching and isoelectric focusing procedures of Perrella et al. [(1978) Anal. Biochem. 88, 212]. Studies of these mutant hybrid hemoglobins have provided evidence for three distinct types of energetic coupling within the hemoglobin tetramer. All alpha 1 beta 2 interface sites examined are involved in cooperativity-linked indirect coupling. Within the context of this indirect "pathway" there exist two different types of direct long-range coupling. One of these classes of direct long-range pathways is linked to cooperative ligand binding while the other class is not. PMID- 2271616 TI - Visible light induced DNA cleavage by the hybrid antitumor antibiotic dynemicin A. AB - Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, effectively breaks DNA strands upon irradiation with visible light of long wavelength. The preferential cutting sites of visible light induced DNA cleavage with dynemicin A are on the 3'-side of purine bases such as in 5'-AT and 5'-GT sequences. The observed nucleotide cutting specificity is remarkably similar to that of NADPH- (or thiol) induced DNA breakage with dynemicin A, suggesting the presence of the same DNA-cleaving intermediate. Indeed, the photoproduct of dynemicin A is chromatographically identical with the reaction product (dynemicin H) of the thiol-activated dynemicin A. On the basis of the present results, a reasonable mechanism for the visible light induced DNA cleavage of dynemicin A has been proposed. PMID- 2271617 TI - DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards. AB - The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7 guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9 aminoacridine chromophores. The results demonstrate that in this series of DNA directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed. PMID- 2271618 TI - Alternating zinc finger motifs in the male-associated protein ZFY: defining architectural rules by mutagenesis and design of an "aromatic swap" second-site revertant. AB - We describe spectroscopic and biochemical studies of native and mutant Zn finger peptides from ZFY, a putative transcription factor encoded by the sex-determining region of the human Y chromosome. The parent peptide, based on ZFY domain 6, exhibits metal-dependent helix formation within a rigid tertiary framework. Nonaromatic substitutions of the consensus aromatic group (Tyr 10----Ser or Lys) are surprisingly compatible with native architecture but result in loss of stability to pH or guanidine denaturation. Remarkably, these perturbations are reverted by a second-site mutation in which an alternative aromatic residue is introduced (Ser 12----Phe). Design of the second-site revertant ("aromatic swap") is based on the ZFY two-finger repeat, a conserved symmetry among the ZFY-related zinc finger proteins, and is in accord with recent 2D NMR structures of Zn finger peptides. These experiments suggest general rules for metal-dependent folding of the Zn finger motif. PMID- 2271619 TI - Construction and expression of human/bovine P45017 alpha chimeric proteins: evidence for distinct tertiary structures in the same P450 from two different species. AB - In the human and bovine adrenal cortex, 17 alpha-hydroxylase (P45017 alpha) catalyzes reactions involved in the production of C21-glucocorticoids (17 alpha hydroxylation) and C19-androgens (17,20-lyase). The bovine and human forms of P45017 alpha share 71% primary sequence identity. Using naturally occurring restriction sites common to cDNAs encoding both human and bovine P45017 alpha, we have constructed bovine/human (bovine amino terminus and human carboxy terminus) and human/bovine (human amino terminus and bovine carboxy terminus) cDNAs that have been expressed in COS 1 cells, and the enzymatic properties of the resultant chimeric proteins have been examined. The three bovine/human chimeras studied have 17 alpha-hydroxylase activities intermediate between those of the wild-type bovine and wild-type human enzymes, although the 17,20-lyase activity of these chimeras is significantly lower than that of either of the wild-type enzymes. Surprisingly, the opposite chimeras (those containing a human amino-terminal sequene and a bovine carboxy-terminal sequence) are all virtually inactive, even though they appear to be expressed at normal levels. These results indicate that the folding of P45017 alpha initiated by the bovine amino terminus can accommodate human P45017 alpha sequences of various lengths to produce a relatively normal 17 alpha-hydroxylase having decreased 17,20-lyase activity. On the other hand, folding initiated by the human P45017 alpha amino terminus does not easily accommodate bovine carboxy-terminal sequences to produce a functional enzyme. Presumably this difference arises from the fact that the tertiary structures of the bovine and human forms of P45017 alpha are sufficiently different so that interchanging sequences will not lead to functional enzymes in a predictable fashion. PMID- 2271620 TI - Characterization and stereochemistry of cofactor oxidation by a type II dihydrofolate reductase. AB - Type II dihydrofolate reductases (DHFRs) encoded by the R67 and R388 plasmids are different both in sequence and in structure from known chromosomal DHFRs. These plasmid-derived DHFRs are responsible for conferring trimethoprim resistance to the host strain. A derivative of R388 DHFR, RBG200, has been cloned and overproduced [Vermersch, P. S., Klass, M. R., & Bennett, G. N. (1986) Gene 41, 289]. With this cloned and overproduced protein, a rapid purification procedure has been developed that yields milligram quantities of apparently homogeneous RBG200 DHFR with a specific activity 1.5-fold greater than that previously reported for the purified R388 protein [Amyes, S. G. B., & Smith, J. T. (1976) Eur. J. Biochem. 61, 597]. The pH versus activity profile and the native molecular weight of RBG200 DHFR were found to be similar to those previously reported for other type II DHFRs but different from those of the known chromosomal DHFRs. Stereospecifically labeled [4(S)-2H,4(R)-1H]NADPH was synthesized and used to determine the stereospecificity of NADPH oxidation by RBG200 DHFR. RBG200 DHFR was found to specifically transfer the pro-R hydrogen of NADPH to dihydrofolate, making it a member of the A-stereospecific class of dehydrogenases. Thus, although RBG200 DHFR is different both in sequence and in structure from known chromosomal enzymes, both enzymes catalyze identical hydrogen-transfer reactions. Two distinct binary RBG200 DHFR-NADP+ complexes were detected by monitoring the 1H NMR chemical shifts and line widths of the coenzyme in the presence of RBG200 DHFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271621 TI - Reactivity of parallel-stranded DNA to chemical modification reagents. AB - Four 25-nt long oligonucleotides containing dA and dT (D1, D2, D3, and D4) which are capable of forming parallel-stranded (ps) or antiparallel-stranded (aps) duplexes have been synthesized [Rippe, K., Ramsing, N. B., & Jovin, T. M. (1989) Biochemistry 28, 9536-9541]. In the present study, the OsO4-pyridine complex (Os,py), diethyl pyrocarbonate (DEPC), KMnO4, and the 1,10-phenanthroline-cuprous complex [(OP)2Cu+] were used to investigate the conformation-dependent reactivity of ps, aps, and single-stranded (ss) oligonucleotides. The products were analyzed by polyacrylamide gel electrophoresis with single-nucleotide resolution. The results confirm the duplex nature of the ps combinations of oligonucleotides and reveal structural differences in comparison with the aps molecules. Under conditions in which ss-DNA is substantially sensitive to Os,py, both the ps and aps duplexes are very unreactive. A similar result was observed with KMnO4 and DEPC, although with the latter reagent the modification pattern of the labeled strands D1* and D4* was slightly different for the parallel than for the antiparallel duplex. The (OP)2Cu+ complex efficiently cleaves the aps but not the ps duplex and shows a preference for TAT steps. We also tested the effect of monovalent and divalent cation concentrations on the chemical reactivity of the ps, aps, and ss species. Elevated NaCl concentration leads to a dramatic increase in the Os,py and KMnO4 modification of ss molecules and the ps, but not the aps, duplex. We attribute the apparent reaction with ps-DNA to a destabilization of this conformation under the conditions of reaction. In contrast, all reactions with DEPC are somewhat depressed at high salt concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271622 TI - Metabolism of the carbocyclic nucleoside analogue carbovir, an inhibitor of human immunodeficiency virus, in human lymphoid cells. AB - Carbovir (CBV) is a highly selective carbocyclic nucleoside inhibitor of HIV replication in human lymphocytes and is potentially useful in the treatment of AIDS [Vince et al. (1988) Biochem. Biophys. Res. Commun. 156, 1046-1053]. Using human lymphoid cells severely deficient in nucleoside kinases, we were able to identify the route of activation of CBV metabolism. The present studies have demonstrated that CBV is anabolized to the mono-, di-, and triphosphates and to guanosine 5'-triphosphate in CCRF-CEM cells. Conversion to GTP amounted to 15-20% of the total analogue nucleotides formed in the cells and may arise from CBV through depurination and salvage via HGPRT. Evidence was obtained that neither deoxycytidine kinase, adenosine kinase, or mitochondrial deoxyguanosine kinase is primarily involved in the initial step of phosphorylation of CBV in CCRF-CEM cells. In contrast, earlier studies [Johnson & Fridland (1989) Mol. Pharmacol. 36, 291-295] showed that a cytosolic 5'-nucleotidase catalyzes the activation of CBV to the monosphosphate. Other biochemical effects examined showed that the nucleobases hypoxanthine and adenine, but not guanine, their respective nucleosides, and the dideoxynucleosides 2',3'-dideoxyinosine, 2',3' dideoxyguanosine, and 3'-azido-3'-deoxythymidine produced significant increased accumulation of CBV nucleotides in CEM cells. The exact mechanism for this potentiation of CBV phosphorylation has not been elucidated but may be due to a modulating effect of intracellular nucleotides on 5'-nucleotidase activity. PMID- 2271623 TI - NMR and computational studies of interactions between remote residues in gangliosides. AB - Conformational preferences of the gangliosides GM1, GM1b, and GD1a have been investigated by using a systematic combination of NMR distance constraints and molecular mechanics calculations. These gangliosides share a common four-sugar core but differ in the number or placement of sialic acid residues attached to the core. Placement of the sialic acid residues is shown to influence the preferred core conformation. The origin of these effects is postulated to be intramolecular interactions of the sialic acid residues with other remote residues. In the case of GM1, hydrogen bonds between the internal sialic acid and an N-acetyl group on GalNAc are suggested. In the case of GD1a, a hydrogen bonding network between the terminal and internal sialic acids is suggested to play a role. PMID- 2271624 TI - Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli. AB - The genes that encode the five known enzymes of the mandelate pathway of Pseudomonas putida (ATCC 12633), mandelate racemase (mdlA), (S)-mandelate dehydrogenase (mdlB), benzoylformate decarboxylase (mdlC), NAD(+)-dependent benzaldehyde dehydrogenase (mdlD), and NADP(+)-dependent benzaldehyde dehydrogenase (mdlE), have been cloned. The genes for (S)-mandelate dehydrogenase and benzoylformate decarboxylase have been sequenced; these genes and that for mandelate racemase [Ransom, S. C., Gerlt, J. A., Powers, V. M., & Kenyon, G. L. (1988) Biochemistry 27, 540] are organized in an operon (mdlCBA). Mandelate racemase has regions of sequence similarity to muconate lactonizing enzymes I and II from P. putida. (S)-Mandelate dehydrogenase is predicted to be 393 amino acids in length and to have a molecular weight of 43,352; it has regions of sequence similarity to glycolate oxidase from spinach and ferricytochrome b2 lactate dehydrogenase from yeast. Benzoylformate decarboxylase is predicted to be 499 amino acids in length and to have a molecular weight of 53,621; it has regions of sequence similarity to enzymes that decarboxylate pyruvate with thiamin pyrophosphate as cofactor. These observations support the hypothesis that the mandelate pathway evolved by recruitment of enzymes from preexisting metabolic pathways. The gene for benzoylformate decarboxylase has been expressed in Escherichia coli with the trc promoter, and homogeneous enzyme has been isolated from induced cells. PMID- 2271625 TI - Engineering enzyme subsite specificity: preparation, kinetic characterization, and X-ray analysis at 2.0-A resolution of Val111Phe site-mutated calf chymosin. AB - Comparison of the three-dimensional structure of bovine chymosin with the structures of homologous aspartic proteinases complexed with peptide inhibitors shows that Val111 in chymosin occupies a position between the specificity subsites S1 and S3. A mutation corresponding to Val111 to Phe has been introduced in an intermediary plasmid construct of prochymosin by bridging its unique restriction sites by a synthetic mutant oligonucleotide duplex. A prochymosin fusion product was expressed in Escherichia coli in such a way that the extension and substitution of the propart does not interfere with the activation of the zymogen. After activation of the crude prochymosin, the enzyme was purified by affinity chromatography on Sepharose with V-dL-P-F-F-V-dL as ligand. This procedure provided large amounts of pure protein as judged by FPLC, the activity/protein ratio, and SDS-PAGE. The enzymatic properties were determined by using a variety of peptide substrates and inhibitors; KM values for the mutant enzyme were approximately twice those of the wild type, but the kcat values were little changed. The mutant enzyme was crystallized, X-ray data were collected to 2.0-A resolution by using a FAST area detector, and the structure was solved by using difference Fourier methods and refined to an R factor of 19.5%. The mutation leads to only local changes in conformation, with the phenylalanine side chain occupying part of the S1 and S3 pockets. This accounts for the increased KM of this mutant for a substrate with a large phenylalanine side chain at P1. It is also consistent with the higher affinity of the mutant for an inhibitor with small side chains at P1 and P3 when compared with the wild-type enzyme. PMID- 2271626 TI - 2D NMR and structural model for a mitochondrial signal peptide bound to a micelle. AB - The 19 amino acid signal peptide of rat liver aldehyde dehydrogenase, possessing a lysine substitution for an arginine and containing 3 extra amino acid residues at the C terminus, was studied by two-dimensional NMR in a dodecylphosphocholine micelle. In this membrane-like environment, the peptide contains two alpha helical regions, both of which are amphiphilic, separated by a hinge region. The helix located closer to the C terminus is more stable than is the helix located near the N terminus. This suggests that the hydrophobic face of the C-terminal helix is buried within the hydrophobic region of the micelle. On the basis of these results a general model for protein translocation is presented in which the C-terminal amphiphilic helix of the signal region in the preprotein first binds to the mitochondrial membrane and then diffuses to the translocation receptor. The receptor then recognizes the N-terminal helix of the signal region, which is not anchored to the membrane. To explain how this signal peptide was imported into isolated mitochondria in the absence of energy or receptor protein [Pak, Y. K., & Weiner, H. (1990) J. Biol. Chem. 265, 14298-14307], a model for signal peptide translocation across a membrane barrier without the need for auxiliary membrane proteins is proposed. In this model the faces of the two helices fold upon each other, resulting in the mutual shielding of positively charged residues by the complementary hydrophilic face of the other amphiphilic helix. PMID- 2271627 TI - Incorporation of a complete set of deoxyadenosine and thymidine analogues suitable for the study of protein nucleic acid interactions into oligodeoxynucleotides. Application to the EcoRV restriction endonuclease and modification methylase. AB - A complete set of dA and T analogues designed for the study of protein DNA interactions has been prepared. These modified bases have been designed by considering the groups on the dA and T bases that are accessible to proteins when these bases are incorporated into double-helical B-DNA [Seeman, N. C., Rosenberg, J. M., & Rich, A. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 804-808]. Each of the positions on the two bases, having the potential to interact with proteins, have been subject to nondisruptive, conservative change. Typically a particular group (e.g., the 6-NH2 of dA or the 5-CH3 of T) has been replaced with a hydrogen atom. Occasionally keto groups (the 2- and 4-keto oxygen atoms of T) have been replaced with sulfur. The base set has been incorporated into the self-complementary dodecamer d(GACGATATCGTC) at the central d(ATAT) sequence. Melting temperature determination shows that the modified bases do not destabilize the double helix. Additionally, circular dichroism spectroscopy shows that almost all the altered bases have very little effect on overall oligodeoxynucleotide conformation and that most of the modified oligomers have a B-DNA type structure. d(GATATC) is the recognition sequence for the EcoRV restriction modification system. Initial rate measurements (at a single oligodeoxynucleotide concentration of 20 microM) have been carried out with both the EcoRV restriction endonuclease and modification methylase. This has enabled a preliminary identification of the groups of the dA and T bases within the d(GATATC) sequence that make important contacts to both proteins. PMID- 2271628 TI - Interaction of the EcoRV restriction endonuclease with the deoxyadenosine and thymidine bases in its recognition hexamer d(GATATC). AB - A set of dA and T analogues suitable for the study of protein DNA interactions have been incorporated into the central d(ATAT) sequence within d(GACGATATCGTC). The individual analogues have one potential protein contact (either a hydrogen bonding group or a CH3 group capable of a van der Waals interaction) deleted. In general, the modified bases do not perturb the overall structure of the dodecamer, enabling results obtained to be simply interpreted in terms of loss of protein DNA contacts. We have used the modified oligodeoxynucleotide set to study the recognition of DNA by the EcoRV restriction endonuclease [recognition sequence d(GATATC)]. The kcat and Km values for the set have been determined, and a comparison with results seen with the parent oligodeoxynucleotide (containing no modified bases) has been carried out. Three classes of results are seen. First, some analogues lead to no change in kinetic parameters, meaning no enzyme contact at the altered site. Second (this is seen for most of the modified oligodeoxynucleotides), a drop in the kcat/Km ratio relative to the parent is observed. This comes mainly from a decrease in kcat, implying that the endonuclease uses the interaction under study to lower the transition-state barrier rather than to bind the substrate. Analyses of these results show that the drop in kcat/Km is what would be expected for the simple loss of a hydrogen bond or a CH3 contact between the enzyme and the oligodeoxynucleotide. This implies a contact of these types at these sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271629 TI - Cross-linking of the 25- and 20-kilodalton fragments of skeletal myosin subfragment 1 by a bifunctional ATP analogue. AB - The bifunctional photoreactive ATP analogue azidonitrobenzoyl-8-azido-ATP (ANB-8 N3-ATP) was synthesized. This ATP analogue carriers photoreactive azido groups at the eighth position of the adenine ring and at the 3' position of ribose. Photolysis of this analogue in the presence of skeletal muscle alpha-chymotryptic subfragment 1 (S-1) resulted in a new 120-kDa band, while photolysis in the presence of the tryptic S-1 produced a new 45-kDa band. The 45-kDa peptide was shown to be combined with the 25-kDa N-terminal and 20-kDa C-terminal fragments since it was labeled with a monoclonal antibody specific for the N-terminal 25 kDa segment of the S-1 heavy chain, and it was also found to retain the fluorescence of (iodoacetamido)fluorescein attached specifically to the SH-1 thiol of the C-terminal 20-kDa segment. These results indicate that the 25- and 20-kDa peptides are in close contact with the ATPase active site. PMID- 2271630 TI - Simple method for selecting catalytic monoclonal antibodies that exhibit turnover and specificity. AB - Monoclonal antibodies were raised against a mono-p-nitrophenyl phosphonate ester to elicit catalytic antibodies capable of hydrolyzing the analogous p-nitrophenyl ester or carbonate. Potential catalytic antibody producing clones were selected, by use of a competitive inhibition assay, on the basis of their affinity for a "short" transition-state analogue, a truncated hapten which maximizes the relative contribution of the transition-state structural elements to binding. Of 30-40 clones that would have been examined on the basis of hapten binding alone, 7 were selected and 4 of these catalyzed the hydrolysis of the relevant p nitrophenyl ester. This competitive inhibition technique represents a general approach for selecting potential catalytic antibodies and significantly increases the probability of obtaining efficient catalytic monoclonal antibodies. Further study of the catalytic antibodies revealed significant rate enhancement (kcat/kuncat approximately 10(4)) and substrate specificity for the hydrolysis of the analogous ester and, for three of the antibodies, of the analogous carbonate. The antibodies displayed turnover, an essential feature of enzymes. Evidence that catalysis occurred at the antibody combining sites was provided by the identity of the binding and the catalysis-inhibition specificity patterns. PMID- 2271631 TI - Cytoplasmic and nuclear distribution of casein kinase II: characterization of the enzyme uptake by bovine adrenocortical nuclear preparation. AB - Casein kinase II (CK II) is a ubiquitous protein kinase that has been found in both nuclear and soluble subcellular fractions and whose precise cellular functions and mechanisms of control remain to be clarified. Using immunocytochemical localization, it was observed that the intracellular distribution of CK II exhibited a striking shift toward an increased nuclear concentration during active proliferation of bovine adrenocortical cells in primary culture. The interaction of CK II with purified adrenocortical cell nuclear preparation was thus examined in vitro. CK II was found to rapidly associate with nuclei in a temperature-dependent and saturable process, resulting in a tight binding of the kinase to nuclear components, as shown by various extraction procedures. This association resulted in a concentration of the kinase in the nuclear preparation about 100-fold that in the medium and exhibited two types of binding sites with Ka of 10(9) and 10(7) M-1, respectively. The nuclear CK II uptake was dependent upon the presence of ATP and was stimulated by a kinase activator such as spermine, although the enzyme activity did not appear to be required for the process. These observations would be in line with a pore mediated, energy-dependent nuclear uptake of the kinase. Since a number of potential nuclear CK II targets have been reported, including the oncoprotein myc, it is suggested that the nuclear translocation of the kinase as characterized in vitro may have a biological significance in living cell, especially in the control of nuclear activities related to cell proliferation and the mechanism of action of growth factors. PMID- 2271632 TI - Asymmetric short-chain phosphatidylcholines: defining chain binding constraints in phospholipases. AB - Several short-chain asymmetric lecithins with a total of 14 carbons in the acyl chains (ranging from 1-lauroyl-2-acetylphosphatidylcholine to 1-hexanoyl-2 octanoylphosphatidylcholine) have been synthesized and characterized. The specific activities of phospholipase A2 from cobra venom, phospholipase A2 from porcine pancreas, and phospholipase C from Bacillus cereus toward these lecithins as micelles have been determined. The results of these kinetic studies allow the definition of hydrophobic binding requirements in the active sites of these water soluble phospholipases. For phospholipase C, with the exception of monomyristoylphosphatidylcholine, each of the asymmetric short-chain lecithins exhibits high activity, comparable to the 14-carbon symmetric short-chain species, diheptanoylphosphatidylcholine. Therefore, for phospholipase C, in addition to the acyl linkages, only a certain degree of hydrophobicity in the fatty acyl chains is requisite for substrate binding and appreciable hydrolysis; there is no chain specificity. The activity of phospholipase A2 from cobra venom toward the same asymmetric lecithins is quite different. As the sn-2 chain lengthens, activity is increased to a maximum for diheptanoyl-PC. Further increase in the number of carbons in the sn-2 chain has no effect on hydrolysis rates. For this enzyme, seven carbons in the sn-2 chain are necessary for optimal activity. In contrast, porcine pancreatic phospholipase A2 activity shows very little dependence on sn-2 chain length. PMID- 2271633 TI - Inhibitors directed to binding domains in neutrophil elastase. AB - Human neutrophil elastase (HNE) can be inhibited by unsaturated fatty acids, including oleic acid [Ashe, B. M., & Zimmerman, M. (1977) Biochem. Biophys. Res. Commun. 75, 194-199; Cook, L., & Ternai, B. (1988) Biol. Chem. Hoppe-Seyler 369, 627-631], but is not affected by saturated fatty acids. We have shown that the interaction of oleic acid with HNE can be characterized by two apparent inhibitory modes: a high-affinity mode (Ki = 48 +/- 3 nM), resulting in partial noncompetitive inhibition (87% residual activity), and a competitive inhibitory mode of lower affinity (Ki = 16 +/- 1 microM). Binding of oleate in the high affinity mode induces a blue shift in the endogenous fluorescence arising from the tryptophan residues in HNE. This shift is maximal in the presence of 1 microM oleate; higher concentrations of fatty acid have no further effect on the fluorescence spectrum. The negatively charged fluorescent ester of oleic acid and hydroxypyrenetrisulfonate (HPTSoleate) interacts with HNE at an apparent single site (Ki = 44 +/- 3 nM), resulting in competitive inhibition. A blue shift in the emission maximum of the pyrene fluorescence at 410 nm and a decrease in the ratio of the intensities of the maximum at 388 and 410 nm indicate that upon binding to HNE the environment of the pyrene ring in HPTSoleate becomes more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271634 TI - Biochemical properties of site-directed mutants of human epidermal growth factor: importance of solvent-exposed hydrophobic residues of the amino-terminal domain in receptor binding. AB - Eight analogues of human epidermal growth factor (hEGF) having specific amino acid substitutions in the beta-sheet structure (residues 19-31) of the amino terminal domain were generated by site-directed mutagenesis. Affinity of the epidermal growth factor (EGF) receptor for each of these mutant hEGF analogues was measured by both radioreceptor competition binding and receptor tyrosine kinase stimulation assays. The relative binding affinities obtained by these two methods were generally in agreement for each hEGF species. The results indicate that hydrophobic residues on the exposed surface of the beta-sheet structure of the amino-terminal domain of hEGF have an important role in the formation of the active EGF-receptor complex. The substitution of hydrophobic amino acid residues, Val-19----Gly, Met-21----Thr, Ile-23----Thr, and Leu-26----Gly, resulted in decreased binding affinity, with the most severe reductions observed with the last two mutants. The mutations Ala-25----Val and Lys-28----Arg introduced amino acid residues resulting in slightly increased receptor binding affinity. Similar to previous results with acidic residues in this region [Engler, D.A., Matsunami, R.K., Campion, S.R., Stringer, C.D., Stevens, A., & Niyogi, S.K. (1988) J. Biol. Chem. 263, 12384-12390], removal of the positive charge in the Lys-28----Leu substitution had almost no effect on binding affinity, indicating the lack of any absolute requirement for ionic interactions at this site. Substitution of Tyr-22, which resulted in decreased receptor binding affinity, provides further indication of the importance of aromatic residues in this region of the molecule, as found earlier with Tyr-29 (cf. reference above).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271635 TI - Two-dimensional 1H and 31P NMR spectra and restrained molecular dynamics structure of a covalent CPI-CDPI2-oligodeoxyribonucleotide decamer complex. AB - CPI-CDPI2 is a synthetic analogue of CC-1065, which is a naturally occurring antitumor antibiotic. Assignment of the 1H NMR spectra of a CPI-CDPI2 oligodeoxyribonucleotide decamer, d-(CGCTTAAGCG)2, complex has been made by two dimensional 1H/1H spectroscopy. The solution structure of the complex was calculated by an iterative hybrid relaxation matrix method combined with NOESY distance restrained molecular dynamics. Refinement proceeded in two steps in which the decamer was initially refined alone and then CPI-CDPI2 was added to the structure to allow initial estimates of drug-DNA contacts. A hybrid matrix/MD refinement was used to better take into account problems associated with spin diffusion. Thus the distances from the 2D NOESY spectra were calculated from the relaxation rate matrix which were evaluated from a hybrid NOESY volume matrix comprising elements from the experimental spectrum and those calculated from an initial structure. The hybrid matrix derived distances were then used in a restrained molecular dynamics procedure to obtain a new structure that better approximates the NOESY spectra. The resulting partially refined structure was then used to calculate an improved theoretical NOESY volume matrix which is once again merged with the experimental matrix until refinement is complete. The efficacy of CC-1065 has been attributed to its minor groove binding and alkylation to the N3 position of adenosine. CPI-CDPI2 appears to bind to the decamer in a similar manner. The effect of CPI-CDPI2 on the decamer's 1H and 31P spectrum was consistent with a minor groove binding motif with the drug alkylating at A17 with the CDPI rings oriented toward the 5'-end of the alkylated strand. In addition, the NMR data support one major adduct but also indicate the presence of a minor adduct. The latter could represent a drug alkylation of the DNA at a secondary site (or alternative orientation of the rings). PMID- 2271636 TI - NMR-derived model for a peptide-antibody complex. AB - The TE34 monoclonal antibody against cholera toxin peptide 3 (CTP3; VEVPGSQHIDSQKKA) was sequenced and investigated by two-dimensional transferred NOE difference spectroscopy and molecular modeling. The VH sequence of TE34, which does not bind cholera toxin, shares remarkable homology to that of TE32 and TE33, which are both anti-CTP3 antibodies that bind the toxin. However, due to a shortened heavy chain CDR3, TE34 assumes a radically different combining site structure. The assignment of the combining site interactions to specific peptide residues was completed by use of AcIDSQRKA, a truncated peptide analogue in which lysine-13 was substituted by arginine, specific deuteration of individual polypeptide chains of the antibody, and a computer model for the Fv fragment of TE34. NMR-derived distance restraints were then applied to the calculated model of the Fv to generate a three-dimensional structure of the TE34/CTP3 complex. The combining site was found to be a very hydrophobic cavity composed of seven aromatic residues. Charged residues are found in the periphery of the combining site. The peptide residues HIDSQKKA form a beta-turn inside the combining site. The contact area between the peptide and the TE34 antibody is 388 A2, about half of the contact area observed in protein-antibody complexes. PMID- 2271637 TI - Interaction mechanism between microtubule-associated proteins and microtubules. A proton nuclear magnetic resonance analysis on the binding of synthetic peptide to tubulin. AB - An amino acid sequence essential for microtubule-associated proteins (MAPs) to bind to microtubules is presented [Aizawa et al. (1989) J. Biol. Chem. 264, 5885 5890]. A synthetic peptide of 23 amino acid residues which corresponded to the sequence [tubulin binding peptide (TBP)] was active in binding to tubulin and inducing its assembly. The TBP-tubulin interaction mechanism was analyzed by proton nuclear magnetic resonance spectroscopy as a simplified model for MAP microtubule interactions. Intraresidue transferred nuclear Overhauser effects (TRNOEs) of TBP in TBP-tubulin mixtures were analyzed, and strong binding of two Val and two Lys residues of TBP to tubulin was detected. Among the sharply peaked signals from tubulin aromatic residues, those due to Tyr ring protons broadened upon mixing with TBP, suggesting the involvement of Tyr residue(s) in the binding with TBP. Irradiation of the tubulin Tyr protons resulted in an intermolecular TRNOE at TBP methyl proton resonances. Evidently, hydrophobic interactions between Val and Tyr residues are important for the binding of TBP to tubulin. Hydrophobic interactions have not been taken into account previously in the widely accepted electrostatic model for the binding of MAPs to microtubules. PMID- 2271638 TI - Mannostatin A, a new glycoprotein-processing inhibitor. AB - Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal alpha-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward alpha- and beta-glucosidase and galactosidase as well as beta-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal alpha-mannosidases, with estimated IC50's of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC50 of about 10-15 nM with p nitrophenyl alpha-D-mannopyranoside as substrate, and about 90 nM with [3H]mannose-labeled GlcNAc-Man5GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity. PMID- 2271639 TI - Conformational studies by circular dichroism, 1H NMR, and computer simulations of bombolitins I and III in aqueous solution containing surfactant micelles. AB - The heptadecapeptides bombolitin I and bombolitin III are two members of a series of biologically active peptides postulated to be membrane active. In order to understand the effects of the membrane on the secondary structure of the peptides, we have carried out the conformational characterization of bombolitins I and III in the presence of SDS micelles using circular dichroism, nuclear magnetic resonance, and computer simulations. The characteristic bands in the circular dichroism spectra indicate an alpha-helix content of approximately 60% in bombolitin III and 70% in bombolitin I. The observation of NOE's quite distinctive for such secondary structure strongly supports the CD results. The conformational preferences of the two bombolitins derived from CD and NMR were then energetically refined with molecular dynamics simulations. The results from the spectroscopic examination were utilized as input for the simulations, the CD results for generation of the initial structure, and the NOE's as constraints during the simulations. The results from the different techniques employed are in complete agreement. PMID- 2271640 TI - Conformations of bombolitins I and III in aqueous solutions: circular dichroism, 1H NMR, and computer simulation studies. AB - The heptadecapeptides bombolitin I and bombolitin III are two of a series of peptides postulated to be biologically active within a membrane environment. In the preceding paper [Bairaktari, E., Mierke, D.F., Mammi, S., & Peggion, E. (1990) Biochemistry (preceding paper in this issue)] the conformational preferences of these peptides in the presence of SDS surfactant micelles, a mimetic for biological membranes, were examined. During these studies the conformations of these peptides were investigated in aqueous solutions by circular dichroism and nuclear magnetic resonance. A large difference was observed for the two peptides. Bombolitin I lacks any observable secondary structure in aqueous solution, independent of temperature, pH, and concentration. In striking contrast, bombolitin III adopts a well-defined alpha-helix at concentrations greater than 1.3 mM. This is indeed surprising given the great similarity of the two peptides. The alpha-helix of bombolitin III is pH dependent, with a great decrease in the observed secondary structure at pH values below 3.5. This observation could only be due to the protonation of the Asp residue at the fifth position. These findings suggest that the secondary structure arises from molecular aggregation of bombolitin III through the formation of a salt bridge involving the Asp side chain. The alpha-helix observed at "high" concentration (greater than 2.5 mM) has been characterized by CD and by the NOE's measured throughout a majority of the peptide. The experimentally determined structure has been energy refined with restrained molecular dynamics. The conformational results from this study are then compared with the conformations found in the presence of surfactant micelles. PMID- 2271641 TI - Phosphorylation of iodopsin, chicken red-sensitive cone visual pigment. AB - The amino acid sequence has been determined for the carboxyl-terminal 41 amino acids of chicken red-sensitive cone pigment, iodopsin. This sequence is distinct from but structurally homologous to that of other visual pigments. It contains a region rich in the hydroxy amino acids serine and threonine. In the related rod cell visual pigment, rhodopsin, such serines and threonines have previously been identified as sites for phosphorylation by rhodopsin kinase. Phosphorylation of photolyzed rhodopsin serves to terminate its ability to function in visual transduction as an activator of G-protein. We have purified and reconstituted both chicken rhodopsin and chicken iodopsin and shown them to be phosphorylated by bovine rhodopsin kinase. Chicken iodopsin has a Km and Vmax similar to but distinguishably different from that for bovine rhodopsin. These results, in conjunction with other data, suggest that visual pigments in cone cells, upon absorption of light, undergo functional processes similar to those of the visual pigments in rod cells. PMID- 2271642 TI - Double-mixing kinetic studies of the reactions of methyl isocyanide and CO with diliganded intermediates of hemoglobin: alpha 2CO beta 2 and alpha 2 beta 2CO. AB - Kinetics of the reactions of CO and methyl isocyanide with two diliganded intermediates of hemoglobin, alpha 2CO beta 2 and alpha 2 beta 2CO, have been studied by double-mixing and microperoxidase methods. The valency hybrids were prepared by high-pressure liquid chromatography. The reaction time courses of ligand combination and dissociation with both of the ligands were biphasic, and in CO combination reaction the zero-time amplitudes of the two phases were independent of the protein concentration. In the presence of 2 M urea the reaction time course was clearly dependent on protein concentration, as the zero time amplitude of the fast phase increased at lower protein concentrations. These two observations indicate that little dissociation of tetramers into dimers occurs in the absence of urea. Consistent with this, the kinetic data for the reactions of CO best fit a reaction model consisting of two tetrameric species not in rapid equilibrium with each other. Various considerations, however, suggest that the reaction model is more appropriately described as 2D in equilibrium R in equilibrium T. The reaction of triliganded species (Hb4(CO)2Me1) with methyl isocyanide was monophasic, and the reaction model suggested a fast T in equilibrium R structural change after the binding of the third ligand. Although the precise structural nature of the two species remains undefined, it is concluded that the biphasicity in the reactions of the two hybrids is characteristic of the diliganded species only and is independent of the nature of the ligand. PMID- 2271643 TI - Peptide substrate specificity of the membrane-bound metalloprotease of Leishmania. AB - The promastigote surface protease (PSP) of Leishmania is a neutral membrane-bound zinc enzyme. The protease has no exopeptidase activity and does not cleave a large selection of substrates with chromogenic and fluorogenic leaving groups at the P1' site. The substrate specificity of the enzyme was studied by using natural and synthetic peptides of known amino acid sequence. The identification of 11 cleavage sites indicates that the enzyme preferentially cleaves peptides at the amino side when hydrophobic residues are in the P1' site and basic amino acid residues in the P2' and P3' sites. In addition, tyrosine residues are commonly found at the P1 site. Hydrolysis is not, however, restricted to these residues. These results have allowed the synthesis of a model peptide, H2N-L-I-A-Y-L-K-K-A T-COOH, which is cleaved by PSP between the tyrosine and leucine residues with a kcat/Km ratio of 1.8 X 10(6) M-1 s-1. Furthermore, a synthetic nonapeptide overlapping the last four amino acids of the prosequence and the first five residues of mature PSP was found to be cleaved by the protease at the expected site to release the mature enzyme. This result suggests a possible autocatalytic mechanism for the activation of the protease. Finally, the hydroxamate derivatized dipeptide Cbz-Tyr-Leu-NHOH was shown to inhibit PSP competitively with a KI of 17 microM. PMID- 2271644 TI - Melting and chemical modification of a cyclized self-splicing group I intron: similarity of structures in 1 M Na+, in 10 mM Mg2+, and in the presence of substrate. AB - C IVS is the cyclized form of the intron from the RNA precursor of the Tetrahymena thermophila large subunit (LSU) ribosomal RNA. C IVS was mapped by chemical modification in 1 M Na+, 0.05 M Na+ and 10 mM Mg2+ (Na+/Mg2+), and Na+/Mg2+ with CUCU substrate. The results suggest the secondary structure is similar for all three conditions. Optical melting curves were also measured for C IVS in 1 M Na+ and Na+/Mg2+ and indicate the secondary structures have similar stabilities under both conditions. Computer predictions of secondary structure and stability are in good agreement with observations. The results suggest that many of the approximations used for computer prediction of secondary structure by free energy minimization are reasonable. PMID- 2271645 TI - Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. AB - A ribozyme derived from the intervening sequence (IVS) of the Tetrahymena preribosomal RNA catalyzes a site-specific endonuclease reaction: G2CCCUCUA5 + G in equilibrium with G2CCCUCU + GA5 (G = guanosine). This reaction is analogous to the first step in self-splicing of the pre-rRNA, with the product G2CCCUCU analogous to the 5'-exon. The following mechanistic conclusions have been derived from pre-steady-state and steady-state kinetic measurements at 50 degrees C and neutral pH in the presence of 10 mM Mg2+. The value of kcat/Km = 9 x 10(7) M-1 min-1 for the oligonucleotide substrate with saturating G represents rate limiting binding. This rate constant for binding is of the order expected for formation of a RNA.RNA duplex between oligonucleotides. (Phylogenetic and mutational analyses have shown that this substrate is recognized by base pairing to a complementary sequence within the IVS). The value of kcat = 0.1 min-1 represents rate-limiting dissociation of the 5'-exon analogue, G2CCCUCU. The product GA5 dissociates first from the ribozyme because of this slow off-rate for G2CCCUCU. The similar binding of the product, G2CCCUCU, and the substrate, G2CCCUCUA5, to the 5'-exon binding site of the ribozyme, with Kd = 1-2 nM, shows that the pA5 portion of the substrate makes no net contribution to binding. Both the substrate and product bind approximately 10(4)-fold (6 kcal/mol) stronger than expected from base pairing with the 5'-exon binding site. Thus, tertiary interactions are involved in binding. Binding of G2CCCUCU and binding of G are independent. These and other data suggest that binding of the oligonucleotide substrate, G2CCCUCUA5, and binding of G are essentially random and independent. The rate constant for reaction of the ternary complex is calculated to be kc approximately equal to 350 min-1, a rate constant that is not reflected in the steady-state rate parameters with saturating G. The simplest interpretation is adopted, in which kc represents the rate of the chemical step. A site-specific endonuclease reaction catalyzed by the Tetrahymena ribozyme in the absence of G was observed; the rate of the chemical step with solvent replacing guanosine, kc( G) = 0.7 min-1, is approximately 500-fold slower than that with saturating guanosine. The value of kcat/Km = 6 x 10(7) M-1 min-1 for this hydrolysis reaction is only slightly smaller than that with saturating guanosine, because the binding of the oligonucleotide substrate is predominantly rate-limiting in both cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271646 TI - Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. AB - The site-specific endonuclease reaction catalyzed by the ribozyme from the Tetrahymena pre-rRNA intervening sequence has been characterized with a substrate that forms a "matched" duplex with the 5' exon binding site of the ribozyme [G2CCCUCUA5 + G in equilibrium with G2CCCUCU + GA5 (G = guanosine); Herschlag, D., & Cech, T.R. (1990) Biochemistry (preceding paper in this issue)]. The rate limiting step with saturating substrate is dissociation of the product G2CCCUCU. Here we show that the reaction of the substrate G2CCCGCUA5, which forms a "mismatched" duplex with the 5' exon binding site at position -3 from the cleavage site, has a value of kcat that is approximately 10(2)-fold greater than kcat for the matched substrate (50 degrees C, 10 mM MgCl2, pH 7). This is explained by the faster dissociation of the mismatched product, G2CCCGCU, than the matched product. With subsaturating oligonucleotide substrate and saturating G, the binding of the oligonucleotide substrate and the chemical step are each partially rate-limiting. The rate constant for the chemical step of the endonuclease reaction and the rate constant for the site-specific hydrolysis reaction, in which solvent replaces G, are each within approximately 2-fold with the matched and mismatched substrates, despite the approximately 10(3)-fold weaker binding of the mismatched substrate. This can be described as "uniform binding" of the base at position -3 in the ground state and transition state [Albery, W.J., & Knowles, J. R. (1976) Biochemistry 15, 5631-5640]. Thus, the matched substrate does not use its extra binding energy to preferentially stabilize the transition state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271647 TI - High-pressure laser photolysis study of hemoproteins. Effects of pressure on carbon monoxide binding dynamics for R- and T-state hemoglobins. AB - The bimolecular association reaction of carbon monoxide to human adult hemoglobin at pH 7, 20 degrees C, was examined as a function of pressure up to 1500 bar by means of high-pressure laser photolysis. The apparent quantum yield for a millisecond recombination reaction decreased with pressure, which was attributed to an increase in the fraction of nanosecond geminate recombination reaction. On the basis of the pressure dependence of the recombination rate, the activation volumes at normal pressure for the binding of carbon monoxide to the R- and T state hemoglobins were determined as -9.0 +/- 0.7 and -31.7 +/- 2.4 cm3 mol-1, respectively. Since the activation volumes for the overall CO association reaction were negative, it seems that the iron-ligand bond formation process mainly contributes to the rate-limiting step for both quaternary structures. The characteristic pressure dependence of the activation volume was observed for the R-state Hb but not for the T-state Hb. At 1000 bar, the activation volume for the R-state Hb was reduced to nearly zero, probably resulting from the contribution of the ligand migration process to the rate-limiting step. The effect of pressure on the activation enthalpy and entropy was also extracted from the data. PMID- 2271648 TI - Characterization of two new members of the pregnancy-specific beta 1-glycoprotein family from the myeloid cell line KG-1 and suggestion of two distinct classes of transcription unit. AB - Pregnancy-specific beta 1-glycoproteins (PSGs) represent a large group (approximately 12-15) of proteins, related to members of the carcinoembryonic antigen family, that are abundant in placental tissue and in the sera of pregnant women. We describe the isolation and characterization of two additional PSG cDNAs, PSG9 and PSG10, whose transcripts are largely expressed in placental tissue and to a lesser extent in some other cell types, including myeloid cells differentiated to granulocytes. PSG9 and PSG10 are representatives of two distinct classes of PSG protein that have N-termini with or without the Arg-Gly Asp motif implicated in adhesion. In addition to this distinction at the amino acid level, our analysis of several PSG cDNAs suggests that the transcription units encoding these proteins may be further distinguished in their 3' untranslated sequences, thus suggesting possibilities for transcriptional regulation of the two major protein classes. PMID- 2271649 TI - pKa's of ionizable groups in proteins: atomic detail from a continuum electrostatic model. AB - A macroscopic electrostatic model is used to calculate the pKa values of the titratable groups in lysozyme. The model makes use of detailed structural information and treats solvation self-energies and interactions arising from permanent partial charges and titratable charges. Both the tetragonal and triclinic crystal structures are analyzed. Half of the experimentally observed pKa shifts (11 out of 21) are well reproduced by calculations for both structures; this includes the unusually high pKa of Glu 35 in the active site. For more than half the pKa's (13 out of 21), there is a large difference (1-3.3 pK units) between the results from the two structures. Many of these correspond to the titrating groups for which the calculations are in error. Since for an ionic strength of 0.1 M the Debye screening between titratable groups leads to a very high effective dielectric constant (the average value for all pairs of titrating groups is approximately 900), near-neighbor interactions dominate the pKa perturbations. Thus, the pKa values are very sensitive to the details of the local protein conformation, and it is likely that side-chain mobility has an important role in determining the observed pKa shifts. PMID- 2271650 TI - Recombinant expression, biochemical characterization, and biological activities of the human MGSA/gro protein. AB - Melanoma growth stimulatory activity (MGSA) is a mitogenic protein secreted by Hs294T melanoma cells that corresponds to the polypeptide encoded by the human gro gene. The MGSA/gro cDNA has been expressed in mammalian cells and the secreted recombinant factor has been purified. Biochemical and biological characterization shows that the recombinant protein is identical with the natural protein and is devoid of posttranslational glycosylation, sulfation, and phosphorylation. The two C-terminal amino acids are proteolytically removed from the mature recombinant MGSA, indicating a length of 71 instead of the predicted 73 amino acids. The recombinant MGSA is mitogenically active on the Hs294T melanoma cells. The purified MGSA competes with interleukin 8 for binding to neutrophil receptors and exhibits neutrophil chemotactic activity equivalent to that of interleukin 8. PMID- 2271651 TI - Effect of increased lipid packing on the surface charge of micelles and membranes. AB - We have investigated the responsiveness of micelle and bilayer surfaces to changes in bulk pH through titrations, and to changes in lipid packing through the application of high hydrostatic pressure using two fluorescent, pH-sensitive surface probes. In micelles, the surface is very sensitive to bulk pH while in phosphatidylcholine and phosphatidic acid bilayers the surface charge changed little through a large pH region. Application of pressure on micelles causes proton dissociation due to the volume reduction achieved from the contraction of water around the charges (electrostriction). However, in bilayers, the effect of electrostriction is greatly reduced, most likely due to the energy needed to expand and hydrate the surface. The sign and amount of change in dissociation the probe undergoes with pressure depend on the initial degree of probe dissociation, which is in turn dependent on the particular surface rather than the charge of the lipid head groups comprising the bilayer. This finding may limit the use of fluorescent probes to determine the exact surface potential. By assuming the change in delta V for proton dissociation from the probe is constant for a given pH, we can calculate the changes in local pH that occur under pressure relative to a neutral or uncharged system. In doing so, we find that the local pH around the probe in bilayers changes very little (approximately 0.1 pH unit or less) in the first 2000 bars. Also, if pressure data are coupled with titration curves, we can determine the change that the bulk pH must undergo to produce the observed change in dissociation seen under pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271652 TI - Chorismate mutase-prephenate dehydrogenase from Escherichia coli. 1. Kinetic characterization of the dehydrogenase reaction by use of alternative substrates. AB - The bifunctional enzyme involved in tyrosine biosynthesis, chorismate mutase prephenate dehydrogenase, has been isolated from extracts of a plasmid-containing strain of Escherichia coli K12 and purified to homogeneity by a modified procedure that involves chromatography on both Matrex Blue A and Sepharose-AMP. Detailed studies of the dehydrogenase reaction have been undertaken with analogues of prephenate that act as substrates. The analogues, which included two of the four possible diastereoisomers of 1-carboxy-4-hydroxy-2-cyclohexene-1 propanoate (deoxodihydroprephenate) as well as D- and L-arogenate, were synthesized chemically. As judged by their V/K values, all analogues were poorer substrates than prephenate. The order of their effectiveness as substrates is prephenate greater than one isomer of 1-carboxy-4-hydroxy-2-cyclohexene-1 propanoate greater than L-arogenate greater than other isomer of 1-carboxy-4 hydroxy-2-cyclohexene-1-propanoate greater than D-arogenate. Thus the dehydrogenase activity is dependent on the degree and position of unsaturation in the ring structure of prephenate as well as on the type of substitution on the pyruvyl side chain. With prephenate as a substrate, the reaction is irreversible because it involves oxidative decarboxylation. By contrast, 1-carboxy-4-hydroxy-2 cyclohexene-1-propanoate undergoes only a simple oxidation, and thus, with this substrate, the reaction is reversible. Steady-state velocity data, obtained by varying substrates over a range of higher concentrations, suggest that the dehydrogenase reaction conforms to a rapid equilibrium, random mechanism with 1 carboxy-4-hydroxy-2-cyclohexene-1-propanoate as a substrate in the forward reaction or with the corresponding ketone derivative as a substrate in the reverse direction. The initial velocity patterns obtained by varying prephenate or 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate over a range of lower concentrations, at different fixed concentrations of NAD, were nonlinear and consistent with a unique model that is described by a velocity equation which is the ratio of quadratic polynomials. An equilibrium constant of 1.4 x 10(-7) M for the reaction in the presence of 1-carboxy-4-hydroxy-2-cyclohexene-1-propanoate indicates that the equilibrium lies very much in favor of ketone production. PMID- 2271653 TI - Chorismate mutase-prephenate dehydrogenase from Escherichia coli. 2. Evidence for two different active sites. AB - The inhibition of the bifunctional enzyme chorismate mutase-prephenate dehydrogenase by substrate analogues, by the end product, tyrosine, and by the protein modifying agent iodoacetate has been investigated. The purpose of the investigations was to determine if the two reactions catalyzed by the enzyme occur at a single active site or at two separate active sites. Evidence in support of the conclusion that the mutase and dehydrogenase reactions are catalyzed at two similar but distinct active sites comes from the following results: (1) A substrate analogue (endo-oxabicyclic diacid) that inhibits competitively the mutase reaction has no effect on the dehydrogenase reaction. (2) Malonic acid and several of its derivatives act as inhibitory analogues of chorismate in the mutase reaction and of prephenate in the dehydrogenase reaction. However, different dissociation constants for their interaction with the free enzyme are obtained from studies on the mutase and dehydrogenase reactions. (3) The kinetics of the inhibition by tyrosine of the mutase reaction in the presence of NAD differ from those of the dehydrogenase reaction. The results confirm that carboxymethylation with iodoacetate of one cysteine residue per subunit eliminates both mutase and dehydrogenase activities and show that the inactivation of the enzyme activities is due to iodoacetate functioning as an active site directed inhibitor. PMID- 2271654 TI - Combined effects of two mutations of catalytic residues on the ketosteroid isomerase reaction. AB - delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) catalyzes the isomerization of delta 5-3-ketosteroids to delta 4-3-ketosteroids by a conservative tautomeric transfer of the 4 beta-proton to the 6 beta-position with Tyr-14 as a general acid and Asp 38 as a general base [Kuliopulos, A., Mildvan, A. S., Shortle, D., & Talalay, P. (1989) Biochemistry 28, 149-159]. Primary, secondary, and combined deuterium kinetic isotope effects establish concerted substrate enolization to be the rate limiting step with the wild-type enzyme [Xue, L., Talalay, P., & Mildvan, A. S. (1990) Biochemistry 29, 7491-7500]. The product of the fractional kcat values resulting from the Y14F mutation (10(-4.7)) and the D38N mutation (10(-5.6)) is comparable (10(-10.3)) to that of the double mutant Y14F + D38N (less than or equal to 10(-10.4)) which is completely inactive. Hence, the combined effects are either additive or synergistic. Quantitatively, similar effects of the two mutations on kcat/KM are found in the double mutant. Despite its inactivity, the Y14F + D38N double mutant forms crystals indistinguishable in form from those of the wild-type enzyme, tightly binds steroid substrates and substrate analogues, and immobilizes a spin-labeled steroid in an orientation indistinguishable from that found in the wild-type enzyme, indicating that the double mutant is otherwise largely intact. It is concluded that the total enzymatic activity of ketosteroid isomerase probably results from the independent and concerted functioning of Tyr-14 and Asp-38 in the rate-limiting enolization step, in accord with the perpendicular or antarafacial orientation of these two residues with respect to the enzyme-bound substrate. Synergistic effects of mutating two residues on kcat and on kcat/KM of enzyme-catalyzed multistep reactions are shown, theoretically, to occur when both residues act independently in the same step, and simple additivity occurs when this step is rate-limiting. Other conditions for additivity of the effects of mutations of kcat and kcat/KM are theoretically explored. PMID- 2271655 TI - Covalent modification and single-strand scission of DNA by a new antitumor antibiotic kapurimycin A3. AB - Kapurimycin A3 is a new antitumor antibiotic isolated from a Streptomyces. It contains the anthrapyrone skeleton and a beta,gamma-unsaturated delta-keto carboxylic acid moiety in the structure. In vitro, kapurimycin causes single strand cleavage of supercoiled pBR322 DNA. The diminished cytotoxicity and DNA cleaving activity for 13-decarboxykapurimycin A3 indicates that the beta, gamma unsaturated delta-keto carboxylic acid moiety is important for the activity of kapurimycin. Kapurimycin A3 binds to calf thymus DNA at 4 degrees C, and the thermal treatment of this adduct results in release of a guanine covalently attached to C-16 of kapurimycin via one of its nitrogen atoms. Thus, the epoxide is the alkylating functional group of kapurimycin, and this is consistent with the lack of DNA cleaving and cytotoxic activities for 14,16-deoxy-14,16 dihydroxykapurimycin. These findings have revealed that DNA strand scission by kapurimycin is due to the alkylation of guanine by ring opening of the epoxide group of kapurimycin, depurination of modified guanine, and presumably subsequent hydrolysis of the phosphate ester backbone at the resultant apurinic sites. PMID- 2271656 TI - Formation and stability of repairable pyrimidine photohydrates in DNA. AB - Ultraviolet irradiation of poly(dG-dC) and poly(dA-dU) in solution produces pyrimidine hydrates that are repaired by bacterial and mammalian DNA glycosylases [Boorstein et al. (1989) Biochemistry 28, 6164-6170]. Escherichia coli endonuclease III was used to quantitate the formation and stability of these hydrates in the double-stranded alternating copolymers poly(dG-dC) and poly(dA dU). When poly(dG-dC) was irradiated with 100 kJ/m2 of 254-nm light at pH 8.0, 2.2% of the cytosine residues were converted to cytosine hydrate (6-hydroxy-5,6 dihydrocytosine) while 0.09% were converted to uracil hydrate (6-hydroxy-5,6 dihydrouracil). To measure the stability of these products, poly(dG-dC) was incubated in solution for up to 24 h after UV irradiation. Cytosine hydrate was stable at 4 degrees C and decayed at 25, 37, and 55 degrees C with half-lives of 75, 25, and 6 h. Uracil hydrate produced in irradiated poly(dA-dU) was stable at 4 degrees C and at 25 degrees C and decayed with a half-life of 6 h at 37 degrees C and less than 0.5 h at 55 degrees C. Uracil hydrate and uracil were also formed in irradiated poly(dG-dC). These experiments demonstrate that UV-induced cytosine hydrate may persist in DNA for prolonged time periods and also undergo deamination to uracil hydrate, which in turn undergoes dehydration to yield uracil. The formation and stability of these photoproducts in DNA may have promoted the evolutionary development of the repair enzyme endonuclease III and analogous DNA glycosylase/endonuclease activities of higher organisms, as well as the development of uracil-DNA glycosylase. PMID- 2271657 TI - Crystal and molecular structure of a DNA duplex containing the carcinogenic lesion O6-methylguanine. AB - The crystal and molecular structure of the first DNA duplex containing the carcinogenic lesion O6MeG has been determined to a resolution of 1.9 A and refined to an R factor of 19%. (d[CGC-(O6Me)GCG])2 crystallizes in the left handed Z DNA form and has crystal parameters and conformational features similar to those of the parent sequence [d(CG)3]2. The methyl groups on O6 of G4 and G10 have C5-C6-O6-O6Me torsion angles of 73 degrees and 56 degrees, respectively, and protrude onto the major groove surface. The base-pairing conformation for the methylated G.C base pairs is of the Watson-Crick type as opposed to a wobble-type conformation that had been proposed in a B DNA fragment. As in other Z DNA structures, a spine of hydration is seen in the minor groove. PMID- 2271658 TI - Enantioselective oxidations of sulfides catalyzed by chloroperoxidase. AB - The chloroperoxidase-catalyzed and horseradish peroxidase catalyzed oxidations of sulfides by tert-butyl and other peroxides have been investigated. The former metal enzyme afforded the corresponding sulfoxides having R absolute configuration in up to 92% enantiomeric excess (ee), whereas the latter gave racemic products. The various factors that control the enantioselectivity of the oxygenation have been examined. PMID- 2271659 TI - Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma. AB - The transfer of [3H]cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t1/2 at 37 degrees C of 51 +/- 8 min and an activation energy of 18.0 kCal mol-1. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major alpha-migrating class (HDL2b) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL2b to smaller alpha HDL (particularly HDL3) driven enzymatically by the lecithin-cholesterol acyltransferase reaction. Rates of transfer among alpha HDL were most rapid from the largest alpha HDL fraction (HDL2b), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell derived isotopic cholesterol indicated that the former preferably utilized the alpha HDL pathway, with little label in pre-beta HDL. The same experiments confirmed earlier data [Castro, G.R., & Fielding, C.J. (1988) Biochemistry 27, 25 29] that cell-derived cholesterol is preferentially channeled through pre-beta HDL. We suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol. PMID- 2271660 TI - Kinetic mechanism of orotate phosphoribosyltransferase from Salmonella typhimurium. AB - The chemical mechanism of the phosphoribosyltransferases (PRTases), although largely unknown, may proceed either via a concerted direct-transfer mechanism or with a two-step mechanism involving a carboxonium-like intermediate. To study this question, we have cloned the Salmonella typhimurium pyrE gene, coding for the enzyme orotate phosphoribosyltransferase (EC 2.2.4.10, OPRTase), and developed a bacterial strain that overproduces the enzyme, which we have purified to homogeneity. Initial velocity and product inhibition studies indicated that S. typhimurium OPRTase follows a random sequential kinetic mechanism. This result was further confirmed by equilibrium isotope exchange studies on two substrate product pairs, PRPP-PPi and OMP-orotate. In addition, the rates of the individual equilibrium isotope exchanges allowed us to conclude that PPi release and PRPP release were the rate-determining steps in the forward and reverse reactions, respectively. Although partial reactions between the two substrate-product pairs, PRPP-PPi and OMP-orotate, were observed, further studies revealed that these exchanges were a result of contaminations. Our results are significant in that S. typhimurium OPRTase, like most PRTases but in contrast to its yeast homologue, follows sequential kinetics. The artifactual partial isotope exchanges found in this work may have implications for similar prior work on the yeast enzyme. In view of the careful isotope effect studies of Parsons and co-workers [Goitein, R.K., Chelsky, D., & Parsons, S.M. (1978) J. Biol. Chem. 253, 2963-2971] and the results obtained by us, we propose that PRTases may involve a direct-transfer mechanism but with low bond order to the leaving pyrophosphate moiety and attacking base. PMID- 2271661 TI - Phosphonate analogue substrates for enolase. AB - Phosphonate analogues in which the bridge between C-2 and phosphorus is a CH2 group are slow substrates for yeast enolase. The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated. Primary deuterium isotope effects of 4-8 on V/KMg, but ones of only 1.15-1.32 on V for dehydration, show that proton removal to give the carbanion intermediate largely limits V/KMg and that a slow step follows which largely limits V (presumably carbanion breakdown). Since there is a D2O solvent isotope effect on V for the reverse reaction of 5, but not an appreciable one on the forward reaction, it appears that the slow rates with phosphonate analogues result from the fact that the carbanion intermediate is more stable than that formed from the normal substrates, and its reaction in both directions limits V. Increased stability as a result of replacement of oxygen by carbon at C-2 of the carbanion is the expected chemical behavior. PMID- 2271662 TI - Characterization of the [4Fe-4S]+ cluster at the active site of aconitase by 57Fe, 33S, and 14N electron nuclear double resonance spectroscopy. AB - 57Fe, 33S, and 14N electron nuclear double resonance (ENDOR) studies have been performed to characterize the [4Fe-4S]+ cluster at the active site of aconitase. Q-band 57Fe ENDOLR of isotopically enriched enzyme, both substrate free and in the enzyme-substrate complex, reveals four inequivalent iron sites. In agreement with Mossbauer studies [Kent et al. (1985) J. Biol. Chem. 260, 6371-6881], one of the iron ions, Fea, which is easily removed by oxidation to yield the [3Fe-4S]+ cluster of inactive aconitase, shows a dramatic change in the presence of substrate. The remaining iron sites, Feb1,2,3, show minor changes when substrate is bound. Methods devised by us for analyzing and simulating ENDOR spectra of a randomly oriented paramagnet have been used to determine the principal values and orientation relative to the g tensor for the hyperfine tensors of three of the four inequivalent iron sites of the [4Fe-4S]+ cluster, Fea, Feb2, and Feb3, in the substrate-free enzyme and the enzyme-substrate complex. The full tensor for the fourth site, Feb1, could not be obtained because its signal is seen only over a limited range of the EPR envelope. 33S ENDOR data for the enzyme-substrate complex using enzyme reconstituted with 33S show that the four inorganic bridging sulfide ions of the [4Fe-4S]+ cube have isotropic hyperfine couplings of A(S) less than 12 MHz, and analysis indicates that they can be divided into two pairs, one with couplings of A(S1) approximately less than 1 MHz and the other with A(S2) approximately 6-12 MHz; the analysis further places these pairs within the cube relative to the iron sites. 33S data for substrate-free enzyme is qualitatively similar and can be completely simulated by two types of S2- ion, with A(S1) approximately 7.5 and A(S2) approximately 9 MHz; the full hyperfine tensors have been determined. The hyperfine values for the two enzyme forms correspond to surprisingly small unpaired spin density on S2-. 14N ENDOR at Q band reveals a nitrogen signal that does not change upon substrate binding. PMID- 2271664 TI - Toward the solution structure of human insulin: sequential 2D 1H NMR assignment of a des-pentapeptide analogue and comparison with crystal structure. AB - 2D 1H NMR studies are presented of des-pentapeptide-insulin, an analogue of human insulin lacking the C-terminal five residues of the B chain. Removal of these residues, which are not required for function, is shown to reduce conformational broadening previously described in the spectrum of intact insulin [Weiss et al. (1989) Biochemistry 28, 9855-9873]. This difference presumably reflects more rapid internal motions in the fragment, which lead to more complete averaging of chemical shifts on the NMR time scale. Sequential 1H NMR assignment and preliminary structural analysis demonstrate retention in solution of the three alpha-helices observed in the crystal state and the relative orientation of the receptor-binding surfaces. These studies provide a foundation for determining the solution structure of insulin. PMID- 2271663 TI - Occurrence and significance of diastereomers of methotrexate alpha-peptides. AB - The L,L diastereomer of methotrexate-alpha-alanine (L,L-MTX-Ala) was synthesized by reaction of alpha-L-glutamyl-L-alanine di-tert-butyl ester with 4-amino-4 deoxy-10-methylpteroic acid, followed by removal of the blocking groups. It was identified by HPLC (C18 reversed-phase silica gel; acetic acid/CH3OH) as the slower of two closely spaced components in DL,L-MTX-Ala prepared previously by a different route [Kuefner et al. (1989) Biochemistry 28, 2288-2297]. The L,L diastereomer was hydrolyzed by pancreatic carboxypeptidase A (to yield MTX and Ala) twice as rapidly as the DL,L mixture. Analysis of the latter by HPLC established that the slower component was hydrolyzed to MTX and that the unreactive, faster component was D,L-MTX-Ala. DL,L-MTX-Arg was resolved by HPLC (NH4OAc/CH3CN) into two closely spaced components, and the diastereomers were partially separated by chromatography on DEAE-Trisacryl (H2O----2% NH4HCO3). Serum carboxypeptidase N hydrolyzed only the slower HPLC component (to yield MTX and Arg), thereby identifying it as the L,L diastereomer. When tested for cytotoxicity against L1210 cells, L,L-MTX-Arg (ID50 = 1.6 X 10(-8) M) was more effective than the D,L diastereomer (ID50 = 2.2 X 10(-7) M). Treatment of MTX with dicyclohexylcarbodiimide and N-hydroxysuccinimide (NHS), followed by hydrolysis of the NHS ester, led to racemization in the L-glutamate moiety of MTX as shown by the fact that the product was hydrolyzed by carboxypeptidase G2 (at the pteroate-Glu bond) only to the extent of ca. 50% compared to the untreated control. These observations have a broad significance, since coupling agents are employed extensively in the derivatization of MTX for attachment to affinity supports and monoclonal antibodies. PMID- 2271665 TI - Physicochemical properties of amaranthin, the lectin from Amaranthus caudatus seeds. AB - Amaranthin is the lectin present in the seeds of Amaranthus caudatus, which specifically binds the T-disaccharide (Gal beta 1,3GalNAc alpha-O-). The lectin is composed of a single type of subunit with Mr = 33,000-36,000 (Rinderle et al., 1989). Equilibrium sedimentation (Mr = 62,900) and low-angle laser light scattering (Mr = 61,400) methods have been used to unambiguously establish the native multimeric structure of amaranthin as a homodimer. These absolute molecular weight methods and the calculated Stokes radius (27.2 A) indicate that the amaranthin dimer is highly compact relative to typical globular proteins, and thus, anomalous molecular weight values are obtained when simple size exclusion chromatography is used to determine the molecular weight of amaranthin. Studies with a homobifunctional cross-linking reagent and amaranthin further support the existence of a lectin homodimer. The stoichiometry of carbohydrate binding was determined to be one T-disaccharide-binding site per amaranthin subunit (Ka = 3.6 X 10(5) M-1). Amaranthin exhibits hydrophobic-binding properties as indicated by binding of 8-anilino-1-naphthalene-sulfonate (Ka = 3.6 X 10(3) M-1) and 6 toluidinyl-2-naphthalenesulfonate (Ka = 2 X 10(4) M-1). Serological studies suggest that amaranthin does not appear to be present in the stems or leaves of the A. caudatus plant, nor were there any indications for the presence of cross reactive material. PMID- 2271666 TI - Metabolic activation of 2-substituted derivatives of myristic acid to form potent inhibitors of myristoyl CoA:protein N-myristoyltransferase. AB - The importance of myristoylation for the proper biological functioning of many acylated proteins has generated interest in the enzymes of the myristoylation pathway and their interactions with substrates and inhibitors. Previous observations that S-(2-oxopentadecyl)-CoA, a nonhydrolyzable methylene-bridged analogue of myristoyl-CoA, was a potent inhibitor of myristoyl-CoA:protein N myristoyltransferase (NMT) [Paige, L. A., Zheng, G.-q., DeFrees, S. A., Cassady, J. M., & Geahlen, R. L. (1989) J. Med. Chem. 32, 1665] prompted a closer examination of the effect of substituents at the 2-position on the interactions of myristic acid and myristoyl-CoA analogues with NMT. As an initial approach, three myristic acid derivatives bearing different substituents at the 2-position, 2-fluoromyristic acid, 2-bromomyristic acid, and 2-hydroxymyristic acid, were selected for study. Both 2-bromomyristic acid and 2-hydroxymyristic acid were available commercially; 2-fluoromyristic acid was prepared synthetically. All three compounds were found to be only weak inhibitors of NMT in vitro. Of the three, 2-bromomyristic acid was the most potent (Ki = 100 microM). In cultured cells, however, 2-hydroxymyristic acid was by far the more effective inhibitor of protein myristoylation. Neither 2-hydroxymyristic acid nor 2-bromomyristic acid significantly inhibited protein palmitoylation in cultured cells, indicating that inhibition was not occurring at the level of acyl-CoA synthetase. Activation of the 2-substituted myristic acid derivatives to their corresponding acyl-CoA thioesters by acyl-CoA synthetase resulted in inhibitors of greatly increased potency. The 2-substituted acyl-CoA analogues, 2-hydroxymyristoyl-CoA, 2 bromomyristoyl-CoA, and 2-fluoromyristoyl-CoA, were synthesized and shown to be competitive inhibitors of NMT in vitro (Ki's = 45, 450, and 200 nM, respectively). These data suggested that the enhanced inhibitory potency of 2 hydroxymyristic acid seen in cells was most probably a result of its metabolic activation to the CoA thioester. The presence of substituents at the 2-position also affected the ability of the acyl group to be transferred by NMT to a peptide substrate. Of the three acyl-CoA analogues, only 2-fluoromyristoyl-CoA served as a substrate for NMT. PMID- 2271667 TI - The self-splicing RNA of Tetrahymena is trapped in a less active conformation by gel purification. AB - When the circular form of the self-splicing intervening sequence of Tetrahymena thermophila was purified by denaturing polyacrylamide gel electrophoresis by standard methods, the rate of its reaction with tetrauridylate decreased 150-fold at 30 degrees C and at least 1000-fold at 0 degrees C. The activity of the self splicing RNA was restored by heating it to high temperature and letting it renature in the presence of Mg2+. The rate of reaction of tetrauridylate with the self-splicing RNA flanked by exons was also greatly decreased by gel purification. The difference in activation energies for the reaction of native and denatured intervening sequences suggests that a substantial conformational rearrangement of the gel-purified RNA occurs prior to reaction. PMID- 2271668 TI - Trends in biochemistry and enzymology of cellulose degradation. PMID- 2271669 TI - A novel minimum ribozyme with oxidoreduction activity. AB - A nucleoside catalyzing the oxidoreduction of NADH and K3Fe(CN)6 was isolated from Torula yeast RNA and also obtained in 0.05% yield by a series of steps: SDS phenol extraction, nuclease P1 digestion, alkaline phosphatase digestion, anion exchange chromatography, and HPLC on an ODS column. Its chemical structure was clearly determined at 5-hydroxycytidine, from the results of FAB-MS and 1H and 13C NMR spectroscopies. The mass spectra, chromatographic behavior, UV spectra, and NMR spectra of this nucleoside from natural and synthetic sources were identical. This is the first report of an RNA catalyst having catalytic activity except for the cleavage and ligation of phosphodiester bonds of RNA. That an RNA has oxidoreduction activity indicates new possibilities for RNAs as "living molecules". 5-Hydroxycytidine may be a vestige of RNAs that formerly possessed metabolizing ability. PMID- 2271670 TI - Remodeling hexose-1-phosphate uridylyltransferase: mechanism-inspired mutation into a new enzyme, UDP-hexose synthase. AB - Hexose-1-phosphate uridylyltransferase catalyzes the interconversion of UDP galactose and glucose-1-P with UDP-glucose and galactose-1-P by a double displacement mechanism through a covalent intermediate (E-UMP), in which UMP is bonded to one of two histidine residues at the active site, H164 or H166. To identify which histidine is the nucleophilic catalyst, we prepared two specific mutants of the enzyme from Escherichia coli, H164G and H166G, in each of which the imidazole ring and methylene carbon of one histidine are deleted. To determine whether the function of the deleted imidazole in these mutants could be carried out by the imidazole ring in uridine 5'-(phosphoimidazolate) (UMP-Im), we examined the mutant proteins for catalytic activity in the reaction of UMP-Im with glucose-1-P to form UDP-glucose and imidazole. The mutant H166G catalyzes this reaction, as well as the reverse reaction, by a sequential kinetic mechanism involving ternary complexes as intermediates. The mutant enzyme also accepts galactose-1-P as a substrate to form UDP-galactose. Hexose-1-P uridylyltransferase does not catalyze these reactions, and H166G does not catalyze the wild-type reaction. The substrate Km values for the mutant enzyme are similar to those for hexose-1-P uridylyltransferase. The value of kcat in the direction of UDP-glucose formation is 1.31 +/- 0.01 s-1, compared with 350 s-1 for hexose-1-P uridylyltransferase, and in the reverse direction kcat is 4.8 +/- 0.4 s-1, compared with 960 s-1 for the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271671 TI - Alternate electron acceptors for medium-chain acyl-CoA dehydrogenase: use of ferricenium salts. AB - Medium-chain acyl-CoA dehydrogenase reduced with octanoyl-CoA is reoxidized in two one-electron steps by two molecules of the physiological oxidant, electron transferring flavoprotein (ETF). The organometallic oxidant ferricenium hexafluorophosphate (Fc+PF6-) is an excellent alternative oxidant of the dehydrogenase and mimics a number of the features shown by ETF. Reoxidation of octanoyl-CoA-reduced enzyme (200 microM Fc+PF6- in 100 mM Hepes buffer, pH 7.6, 1 degree C) occurs in two one-electron steps with pseudo-first-order rate constants of 40 s-1 and about 200 s-1 for k1 and k2, respectively. The reaction is comparatively insensitive to ionic strength, and evidence of rate saturation is encountered at high ferricenium ion concentration. As observed with ETF, the free two-electron-reduced dehydrogenase is a much poorer kinetic reductant of Fc+PF6-, with rate constants of 3 s-1 and 0.3 s-1 (for k1 and k2, respectively) using 200 microM Fc+PF6-. In addition to the enoyl-CoA product formed during the dehydrogenation of octanoyl-CoA, binding a number of redox-inert acyl-CoA analogues (notably 3-thia- and 3-oxaoctanoyl-CoA) significantly accelerates electron transfer from the dehydrogenase to Fc+PF6-. Those ligands most effective at accelerating electron transfer favor deprotonation of reduced flavin species in the acyl-CoA dehydrogenase. Thus this rate enhancement may reflect the anticipated kinetic superiority of anionic flavin forms as reductants in outer sphere electron-transfer processes. Evidence consistent with the presence of two distinct loci for redox communication with the bound flavin in the acyl-CoA dehydrogenase is presented. PMID- 2271672 TI - Resistance to receptor-mediated degradation of a murine epidermal growth factor analogue (EGF-Val-47) potentiates its mitogenic activity. AB - In most cell types two classes of epidermal growth factor (EGF) receptors can be found: a major class that binds EGF with relatively low affinity and a minor class that binds with very high affinity. Structure-function studies have shown that mutations at amino acid 47 in the EGF molecule severely reduce its affinity for the EGF receptor but do not cause preferential binding to one or the other subclass of receptors. Using three EGF derivatives with a mutation at amino acid 47 (Ser-47, Leu-37-Tyr-47, and Val-47), we have investigated the relative contribution of the two receptor subclasses to the EGF-dependent mitogenic response. We show that mitogenicity correlates exclusively with occupancy of the high-affinity receptor and that full occupancy of this subclass is required for maximal stimulation. In addition we demonstrate that for the EGF-Val-47 analogue this requirement can be abrogated and half-maximal biological activity reached with a high-affinity receptor occupancy of only 8%. While the rate of internalization did not significantly differ between EGF-Val-47 and native mEGF, the analogue was much more resistant to degradation by cellular proteases and, after binding and receptor-mediated internalization, was released into the medium predominantly in an intact form. We propose that the increased mitogenicity of EGF-Val-47 is due to its prolonged half-life, resulting in continued occupancy of the high-affinity EGF receptor. PMID- 2271673 TI - Ligand exclusion on acetylcholinesterase. AB - This paper examines covalent reactivity of AchE with respect to cationic and uncharged methylphosphonates and substrates in the absence and presence of cationic ligands selective for the active center and the peripheral anionic site. The organophosphorus inhibitors are enantiomeric alkyl methylphosphonothioates (1 5) containing cycloheptyl and isopropyl phosphono ester groups and S-methyl, S-n pentyl, and S-[beta-(trimethylammonio)ethyl] leaving groups; these agents differ in their configuration about phosphorus and their steric, hydrophobic, and electrostatic characteristics. The synthetic substrates examined are acetylthiocholine, p-nitrophenyl acetate, and 7-acetoxy-4-methylcoumarin (7AMC). Antagonism of the methylphosphonothioate reaction by cationic ligands is strongly dependent on the nature of both the cation and the methylphosphonate but independent of the configuration about phosphorus. While all cations cause linear mixed inhibition of acetylthiocholine hydrolysis, there are observed a variety of inhibition patterns of 7AMC and p-nitrophenyl acetate hydrolysis that are distinctly nonlinear, as well as patterns in which the reciprocal plots intersect in the upper right quadrant. Strong antagonism of cationic (methylphosphonyl)thiocholines correlates very well with linear inhibition of acetylthiocholine. Ligands that cause only negligible antagonism of the uncharged methylphosphonates display nonlinear inhibition of uncharged substrates. These relationships, since they are most pronounced for peripheral site ligands and are strongly dependent on the charge carried by the reactant, suggest that the peripheral anionic site alters enzyme reactivity through an electrostatic interaction with the net negative active center. Such behavior indicates a potential role for the peripheral anionic site in conserving AchE catalytic efficiency within a narrow range of values. PMID- 2271674 TI - Intrinsic fluorescence of binding-site fragments of the nicotinic acetylcholine receptor: perturbations produced upon binding alpha-bungarotoxin. AB - Synthetic peptides corresponding to sequences contained within residues 173-204 of the alpha-subunit in the nicotinic acetylcholine receptor (nAChR) of Torpedo californica bind the competitive antagonist alpha-bungarotoxin (BGTX) with relative high affinity. Since the synthetic peptide fragments of the receptor and BGTX each contain a small number of aromatic residues, intrinsic fluorescence studies were used to investigate their interaction. We examined a number of receptor-derived peptide fragments of increasing length (4-32 amino acids). Changes in the lambda max and quantum yield with increasing polypeptide chain length suggest an increase in the hydrophobicity of the tryptophan environment. When selective excitation and subtraction were used to reveal the tyrosine fluorescence of the peptides, a significant red shift in emission was observed and was found to be due to an excited-state tyrosinate. The binding of BGTX to the receptor-derived peptide fragments resulted in a large increase in fluorescence. In addition, at equilibrium, the lambda max of tryptophan fluorescence was shifted to shorter wavelengths. The. fluorescence enhancement, which was saturable with either peptide or BGTX, was used to determine the dissociation constants for the complexes. At pH 7.4, the apparent Kd for a dodecameric peptide (alpha 185-196), consisting of residues 185-196 in the alpha subunit of the nAChR from Torpedo californica, was 1.4 microM. The Kd for an 18 mer (alpha 181-198), consisting of residues 181-198 of the Torpedo alpha-subunit, was 0.3 microM. No binding or enhanced fluorescence was observed with an irrelevant synthetic peptide of comparable composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271675 TI - Modulation of phospholipid acyl chain order by cholesterol. A solid-state 2H nuclear magnetic resonance study. AB - The effect of cholesterol on the acyl chain order of three glycerophosphocholines with 14, 16, and 18 carbons per acyl chain, namely, di(14:0)PC, di(16:0)PC, and di(18:0)PC, above the gel to liquid-crystalline phase transition temperature was investigated by using 2H nuclear magnetic resonance spectroscopy. Average acyl chain lengths were calculated from the segmental order parameters (Smol) for the sn-1 and the sn-2 chains in the absence of cholesterol and at 3:1, 2:1, and 1:1 mole ratios of phospholipid-cholesterol. The three binary mixtures of cholesterol with phosphatidylcholines are in the liquid-ordered (lo) phase. For all the three phosphatidylcholine-cholesterol systems, the distance from the carbonyl groups to the terminal methyl groups is shorter than the length of the cholesterol molecule. A molecular model for the lo phase consistent with these observations has in a statistical sense a part of each cholesterol molecule in one monolayer extending into the other monolayer. This results in a packing arrangement akin to that in interdigitated systems. On the basis of the effect of cholesterol on phospholipid acyl chain orientational order, it is suggested that the liquid disordered (ld) phase at low cholesterol concentrations corresponds to a packing mode in which the cholesterol molecule spans the entire transbilayer hydrophobic region. A molecular mechanism is proposed in which increasing the concentration of cholesterol has the effect of stretching the acyl chains of phospholipids by increasing the population of trans conformers up to a stage where the hydrophobic length is considerably longer than the cholesterol molecule. Beyond this concentration, the partially interdigitated phase forms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271676 TI - Electrostatic contributions to the binding of myosin and myosin-MgADP to F-actin in solution. AB - The ionic strength dependence of skeletal myosin subfragment 1 (S1) binding to unregulated F-actin was measured in solutions containing from 0 to 0.50 M added lithium acetate (LiOAc) in the absence and presence of MgADP. The data were analyzed by using a theory based on an ion interaction model that is rigorous for high ionic strength solutions [Pitzer, K. S. (1973) J. Phys. Chem. 77, 268-277] in order to obtain values for K, the equilibrium association constant when the ionic strength is zero, and for [zMzA[, the absolute value of the product of the net electric charges of the actin binding site on myosin (zM) and the myosin binding site on actin (zA). The presence of MgADP reduced K by a factor of 10, as expected, and reduced [zMzA[ by about 1 esu2. Because the presence of MgADP is not likely to change the net charge of the myosin binding site on actin, these data are consistent with a model in which MgADP binding to S1 reduces its affinity for actin by a mechanism that reduces the net electric charge of the acting binding site on S1. The value of [zMzA[ in the absence of ADP was 8.1 +/- 0.9 esu2, which, if one uses integer values, suggests that zM and zA are in the 8+ to 1+ esu and 1- to 8- esu ranges, respectively. ADP binding then reduces zM to the 7+ to 0.88+ esu range. PMID- 2271677 TI - Heterogeneous initiation due to slippage at the bacteriophage 82 late gene promoter in vitro. AB - RNAs synthesized in vitro by purified Escherichia coli RNA polymerase from a bacteriophage 82 promoter are heterogeneous at the 5' end. We show that this heterogeneity results from variable addition of extra adenine residues, allowed by slippage of the initial oligonucleotide pppAAA-OH against its DNA template sequence TTT. Slippage backward by one base allows another A to be added, giving pppAAAA-OH, and this cycle can continue more than 20 times before it is ended by incorporation of UMP encoded by the fourth template base A. Slippage is abolished by mutation of the TTT template sequence to TGT and is sensitive to the concentrations of UTP and ATP in the reaction mixture. Analysis of deletions, substitutions, and point mutants implies that the slippage reaction requires only the existence of TTT at the initiation site of the template strand, although changes in neighboring nucleotides slightly affect its efficiency. PMID- 2271678 TI - Analysis of the changes in the structure and hydration of the nucleosome core particle at moderate ionic strengths. AB - In order to better understand the conformational changes induced in the nucleosome core particle by changes in the ionic strength of the media in the range from 0.1 to 0.6 M NaCl, we have conducted a very detailed structural analysis, combining circular dichroism, DNase I digestion, and sedimentation equilibrium. The results of such analysis indicate that the secondary structure of both DNA and histones exhibits small (approximately 5%) but noticeable changes as the salt increases within this range. In the case of DNA, the data are consistent with a trend toward a more relaxed secondary structure. The DNase I pattern of digestion is also altered by the salt and suggests a DNA relaxation around the flanking ends. From the hydrodynamic measurements, we also observe a significant change in the virial coefficients of the particle as the salt increases, which in turn are in very good agreement with the theoretically expected values. Furthermore, the preferential hydration parameter is also found to increase with the salt. We believe that the self-dependent conformational change of the nucleosome core particle is the result of the conjunction of all these subtle changes. Yet, from the present data, their exact relationship to the tertiary structure of the whole particle at the different ionic strengths cannot be exactly defined. PMID- 2271679 TI - Length of the acyl carbonyl bond in acyl-serine proteases correlates with reactivity. AB - Resonance Raman (RR) spectroscopy has been used to obtain the vibrational spectrum of the acyl carbonyl group in a series of acylchymotrypsins and acylsubtilisins at the pH of optimum hydrolysis. The acyl-enzymes, which utilize arylacryloyl acyl groups, include three oxyanion hole mutants of subtilisin BPN', Asn155Leu, Asn155Gln, and Asn155Arg, and encompass a 500-fold range of deacylation rate constants. For each acyl-enzyme a RR carbonyl band has been identified which arises from a population of carbonyl groups undergoing nucleophilic attack in the active site. As the deacylation rate (k3) increases through the series of acyl-enzymes, the carbonyl stretching band (vC = O) is observed to shift to lower frequency, indicating an increase in single bond character of the reactive acyl carbonyl group. Experiments involving the oxyanion hole mutants of subtilisin BPN' indicate that a shift of vC = O to lower frequency results from stronger hydrogen bonding of the acyl carbonyl group in the oxyanion hole. A plot of log k3 against vC = O is linear over the range investigated, demonstrating that the changes in vC = O correlate with the free energy of activation for the deacylation reaction. By use of an empirical correlation between carbonyl frequency (vC = O) and carbonyl bond length (rC = O) it is estimated that rC = O increases by 0.015 A as the deacylation rate increases 500-fold through the series of acyl-enzymes. This change in rC = O is about 7% of that expected for going from a formal C = O double bond in the acyl enzyme to a formal C-O single bond in the tetrahedral intermediate for deacylation. The data also allow us to estimate the energy needed to extend the acyl carbonyl group along its axis to be 950 kJ mol-1 A-1. PMID- 2271680 TI - Structure and polymorphism of saturated monoacid 1,2-diacyl-sn-glycerols. AB - The 1,2-diacyl-sn-glycerols (1,2-DGs) are the predominant naturally occurring isomer found in cell membranes, lipid droplets, and lipoproteins. They are involved in the metabolism of monoacylglycerols, triacylglycerols, and phospholipids. The 1,2-DGs participate in the activation of protein kinase C, in phosphorylation of target proteins, and in transduction of extracellular signals into the cell. We have undertaken a study of the physical properties of a homologous series of synthetic optically active diacylglycerols. Stereospecific 1,2-diacyl-sn-glycerols were synthesized with saturated fatty acyl chains of 12, 16, 18, 22, and 24 carbons in length. Their polymorphic behavior was examined by differential scanning calorimetry and X-ray powder diffraction. The solvent crystallized form for all the 1,2-DGs packs in the orthorhombic perpendicular subcell (beta') and melts with a single sharp endotherm to an isotropic liquid. On quenching, the C12, C16 and C18 compounds pack in a hexagonal subcell (alpha), whereas the C22 and C24 pack in a pseudohexagonal subcell (sub-alpha). The sub alpha phase reversibly converts to the alpha phase. The long spacings of these compounds in both the alpha and beta' phases increase with chain length. In the alpha and beta' phases, the acyl chain tilts were found to be 90 degrees and 62 degrees from the basal methyl plane. The polymorphic behavior of 1,2-diacyl-sn glycerol is quite different from that of the corresponding monoacid saturated 1,3 diacylglycerols which form two beta phases with triclinic parallel subcells. PMID- 2271681 TI - pH-dependent semiquinone formation by methylamine dehydrogenase from Paracoccus denitrificans. Evidence for intermolecular electron transfer between quinone cofactors. AB - The quinonoid confactors of Paracoccus denitrificans methylamine dehydrogenase exhibited a pH-dependent redistribution of electrons from the 50% reduced plus 50% oxidized to the 100% semiquinone redox form. This phenomenon was only observed at pH values greater than 7.5. The semiquinone was not readily reduced by addition of methylamine, consistent with the view that this substrate donates two electrons at a time to each cofactor during catalysis. Once formed at pH 9.0, no change in redox state from 100% semiquinone was observed when the pH was shifted to 7.5, suggesting that the requirement of high pH was for formation and not stability of the semiquinone. The rate of semiquinone formation exhibited a first-order dependence on the concentration of methylamine dehydrogenase, indicating that this phenomenon was a bimolecular process involving intermolecular electron transfer between reduced and oxidized cofactors. The rate of semiquinone formation decreased with decreasing ionic strength, suggesting a role for hydrophobic interactions in facilitating electron transfer between methylamine dehydrogenase molecules. Methylamine dehydrogenase was covalently modified with norleucine methyl ester in the presence of 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide (EDC). This modification did not affect the catalytic activity of the enzyme but greatly inhibited the intermolecular redistribution of electrons at high pH. This modification also prevented subsequent cross-linking by EDC of the large subunit of methylamine dehydrogenase to amicyanin, the natural electron acceptor for this enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271683 TI - Coupled responses of the regions near cysteine-190 and the carboxy terminus of rabbit cardiac tropomyosin: fluorescence and circular dichroism studies. AB - Rabbit cardiac tropomyosin was labeled at Cys-190 with either N-(1 pyrenyl)iodoacetamide (Py) or 6-acryloyl-2-(dimethylamino)naphthalene (AD, acrylodan). Half of the labeled sample then was treated with carboxypeptidase A to produce an identically labeled nonpolymerizable form of tropomyosin, NPTM. Investigation of temperature-dependent changes in pyrene excimer emission, acrylodan fluorescence polarization, and tyrosyl circular dichroism in different samples of tropomyosin and NPTM reveals that absence of the COOH-terminal portion of tropomyosin modifies the response of the Cys-190 region to heat. Removal of the COOH terminus releases certain conformational constraints from the coiled coil back to and including the Cys-190 region without causing a severe drop in the net alpha-helical content of the protein. Observation of changes in pyrene excimer fluorescence and in fluorescence polarization of acrylodan with time after addition of carboxypeptidase A to samples of labeled tropomyosin directly demonstrates this relaxation process. Thermally induced reduction in tyrosyl circular dichroism, together with consideration of the distribution of tyrosyl residues on tropomyosin, also supports the proposal. PMID- 2271682 TI - Mechanism of inhibition of mammalian tumor and other thymidylate synthases by N4 hydroxy-dCMP, N4-hydroxy-5-fluoro-dCMP, and related analogues. AB - N4-Hydroxy-dCMP (N4-OH-dCMP), N4-methoxy-dCMP (N4-OMe-dCMP), and their 5-fluoro congeners (syntheses of which are described) were all slow-binding inhibitors of Ehrlich carcinoma thymidylate synthase (TS), competitive with respect to dUMP, and had differing kinetic constants describing interactions with the two TS binding sites. N4-OH-dCMP was not a substrate (no dihydrofolate produced; no tritium released with 5-3H-labeled molecule), and its inactivation of TS was methylenetetrahydrofolate-dependent, hence mechanism-based, with arrest of a step posterior to addition of cofactor and blocking abstraction of the C(5) hydrogen. Ki values for N4-OH-dCMP and its 5-fluoro analogue were in the range 10(-7) - 10( 8) M, 2-3 orders of magnitude higher for the corresponding N4-OMe analogues. The 5-methyl analogue of N4-OH-dCMP was 10(4)-fold less potent, pointing to the anti rotamer of the imino form of exocyclic N4-OH, relative to the ring N(3), as the active species. This is consistent with weaker slow-binding inhibition of the altered enzyme from 5-FdUrd-resistant, relative to parent, L1210 cells by both FdUMP and N4-OH-dCMP, suggesting interaction of both N4-OH and C(5)-F groups with the same region of the active center. Kinetic studies with purified enzyme from five sources, viz., Ehrlich carcinoma, L1210 parental, and 5-FdUrd-resistant cells, regenerating rat liver, and the tapeworm Hymenolepis diminuta, demonstrated that addition of a 5-fluoro substituent to N4-OH-dCMP increased its affinity from 2- to 20-fold for the enzyme from different sources.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271684 TI - An EXAFS study of the interaction of substrate with the ferric active site of protocatechuate 3,4-dioxygenase. AB - X-ray crystallographic studies of the intradiol cleaving protocatechuate 3,4 dioxygenase from Pseudomonas aeruginosa have shown that the enzyme has a trigonal bipyramidal ferric active site with two histidines, two tyrosines, and a solvent molecule as ligands [Ohlendorf, D.H., Lipscomb, J.D., & Weber, P.C. (1988) Nature 336, 403-405]. Fe K-edge EXAFS studies of the spectroscopically similar protocatechuate 3,4-dioxygenase from Brevibacterium fuscum are consistent with a pentacoordinate geometry of the iron active site with 3 O/N ligands at 1.90 A and 2 O/N ligands at 2.08 A. The 2.08-A bonds are assigned to the two histidines, while the 1.90-A bonds are associated with the two tyrosines and the coordinated solvent. The short Fe-O distance for the solvent suggests that it coordinates as hydroxide rather than water. When the inhibitor terephthalate is bound to the enzyme, the XANES data indicate that the ferric site becomes 6-coordinate and the EXAFS data show a beat pattern which can only be simulated with an additional Fe O/N interaction at 2.46 A. Together, the data suggest that the oxygens of the carboxylate group in terephthalate displace the hydroxide and chelate to the ferric site but in an asymmetric fashion. In contrast, protocatechuate 3,4 dioxygenase remains 5-coordinate upon the addition of the slow substrate homoprotocatechuic acid (HPCA). Previous EPR data have indicated that HPCA forms an iron chelate via the two hydroxyl functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271685 TI - Spin-echo 1H NMR studies of differential mobility in gizzard myosin and its subfragments. AB - The unexpectedly narrow resonances in the 1H NMR spectra of gizzard myosin, heavy meromyosin, and subfragment 1 were examined by spin-echo NMR spectroscopy. These resonances originated predominantly in the myosin heads, or subfragment 1 units. Smooth muscle myosin undergoes a dramatic change in hydrodynamic properties and can exist either as a folded (10S) or as an extended (6S) species. Factors that influence this transition, namely, ionic strength and phosphorylation (or thiophosphorylation), were varied in the NMR experiments. T2 relaxation experiments on dephosphorylated myosin indicated several components of different relaxation times that were not influenced by changes in ionic strength. Our experiments focused on the components with longer relaxation times, i.e., corresponding to nuclei with more mobility, and these were observed selectively in a spin-echo experiment. With dephosphorylated myosin and HMM, increases in ionic strength caused an increased intensity in several of the narrower resonances. The ionic strength dependence of these changes paralleled that for the 10S to 6S transition. With thiophosphorylated myosin and HMM, changes in ionic strength also influenced the intensities of the narrower resonances, and in addition changes in the 1H NMR spectrum due to thiophosphorylation were observed. The narrow resonances seen with myosin and HMM were observed with S1, but the spin-echo spectra of S1 were not influenced either by changes in ionic strength or by phosphorylation. These results suggest that a fraction of the 1H resonances in smooth muscle myosin and its fragments originates from both aliphatic and aromatic residues of increased mobility compared to the mobility expected from hydrodynamic properties of these proteins. In general, the intensities of these residues increase with increasing ionic strength, and this is consistent with an increase in the percentage of mobile residues during the 10S to 6S transition. Segmental flexibility appeared also to be influenced by phosphorylation within the 6S conformation. These changes were not detected in the isolated myosin heads and thus required a higher order of structure, either the subfragment 2 region or the interaction of myosin heads. PMID- 2271686 TI - Metabolism and intracellular transport of glycosphingolipids. PMID- 2271687 TI - A tetrahedral zinc(II)-binding site introduced into a designed protein. AB - The ultimate goal of protein engineering is to create novel proteins which will adopt predetermined structures, bind specified ligands, and catalyze new reactions. Here we describe the successful introduction of metal-binding activity into a model four helix bundle protein. The designed binding site is tetrahedral and is formed by two Cys and two His ligands on adjacent helices. We have introduced this site into the protein and characterized the binding activity. Using 65Zn(II), we have shown that the protein binds Zn(II), that the sulfhydryls are essential for binding, and that binding occurs to the protein monomer. The designed protein binds metals with high affinity: we estimate the dissociation constants as 2.5 X 10(-8) M for Zn(II) and 1.6 X 10(-5) M for Co(II). The characteristic absorption spectrum of the Co(II)-substituted protein fully supports the model of a tetrahedral binding site comprised of two Cys and two His ligands. Circular dichroism studies indicate that no significant changes in secondary structure occur between the metal-bound and metal-free forms of the protein. However, the metal-bound form is substantially stabilized toward denaturation by GuHCl compared to the metal-free form. PMID- 2271688 TI - Size and structure of antigen-antibody complexes: thermodynamic parameters. AB - The role of antigen-antibody (Ag-Ab) complexes in the immune response depends, in part, on the size of the complexes. Previously, we combined electron microscopy with classical and quasi-elastic light scattering to characterize the molecular weight distribution and the conformation of Ag-Ab complexes made from bovine serum albumin (BSA) and pairs of anti-BSA monoclonal antibodies at a single concentration and Ag:Ab molar ratio. In this report, the molecular weight distribution of Ag-Ab complexes was determined by classical light scattering at a single Ag:Ab ratio and over a range of concentrations, and binding of BSA to pairs of MAb was determined by radioimmunoassay at several Ag:Ab molar ratios. A thermodynamic model was developed for the equilibrium size distribution of Ag-Ab complexes formed between a pair of MAb, each with unique affinity and specificity, and an Ag containing a single epitope for each of the pair of MAb. The combined experimental data were used in conjunction with the model to determine the values of cyclization and polymerization constants. Successful determination of the parameters required data from both classical light scattering and electron microscopy. Cyclization constants were lower than those reported in other studies of Ag-Ab complexes; this may be attributable to our use of a protein Ag, as compared to a divalent hapten. In two out of three cases, cyclization constants increased with increasing number of Ab in the complex, in contrast to previous assumptions. The validity of the thermodynamic model was further shown by its ability, in combination with conformational and hydrodynamic model, to predict the hydrodynamic radius of the complexes over a wide range of experimental conditions. PMID- 2271689 TI - Induction of G.C to A.T transitions by the acridine half-mustard ICR-191 supports a mispairing mechanism for mutagenesis by some bulky mutagens. AB - As the most nucleophilic atom in DNA, the guanine N7 atom is a major site of attack for a large number of chemical mutagens as well as chemotherapeutic agents. Paradoxically, while methylation of guanine N7 is believed to be largely nonmutagenic, aflatoxin B1, among the most potent mutagens, appears to exert its mutagenic activity through adduction at this site. On the basis of an analysis of the specificity of mutations induced by various adduct forms of aflatoxin B1, we have previously proposed mechanisms that can both resolve the paradox and account for the specificity of mutagenesis by aflatoxin B1. The hypothesized mechanisms specify how a bulky guanine N7 lesion can promote G.C to A.T transitions as well as frame-shift mutations. Since the proposed mechanisms are in principle lesion independent, a simple test of the proposed mechanisms would be to examine the specificity of mutations induced by a structurally different bulky guanine N7 adduct. Toward this goal, M13 replicative form DNA was subjected to in vitro adduction with the acridine mutagen ICR-191 and transfected into Escherichia coli. Mutations in the LacZ(alpha) gene segments were scored and defined at the sequence level. The results show that ICR-191 adduction induces both base substitutions and frame shifts with near-equal efficiency. A clear majority of base substitutions were G.C to A.T transitions. On the other hand, unlike aflatoxin B1 which could induce both -1 and +1 frameshifts, ICR-191 appears to predominantly induce +1 frame shifts. This preference appears to arise by lesion dependent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271690 TI - Phospholipids chiral at phosphorus. Dramatic effects of phosphorus chirality on the deuterium NMR properties of the choline head group of phospholipids in the liquid crystalline phase. AB - To probe the motional and conformational properties of the choline head group of 1,2-dipalmitoyl-sn-glycero-3-thiophosphocholine (DPPsC), the Rp, Sp, and Rp + Sp isomers of [alpha-D2]DPPsC, [beta-D2]DPPsC, and [delta-D9]DPPsC in the subgel, gel, and liquid crystalline phases were investigated with deuterium NMR, and the results were compared with those of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) labeled at the same positions. In the subgel phase (5 degrees C) all isomers of [alpha-D2]DPPsC and [beta-D2]DPPsC displayed amorphous line shapes characteristic of a restricted and disordered motional environment, whereas [delta-D9]DPPsC showed narrower and symmetric line shapes indicating substantial motions. For all three labeled positions the apparent line width of the Rp isomer is larger than those of Sp and Rp + Sp isomers, and the amorphous line shape of the Rp isomer also persists at 25 and 35 degrees C, which confirm the previous observation that the Rp isomer is unusually stable in the subgel phase and suggest that the Rp isomer is more rigid than the other isomers in the choline head group. In the gel phase (25 and 35 degrees C) narrower and symmetric line shapes were observed for Sp and Rp + Sp isomers, and the apparent line widths were comparable to those of DPPC. In the liquid crystalline phase there are dramatic differences between the spectra of DPPC and different isomers of DPPsC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271691 TI - Interaction of a macrocyclic bisacridine with DNA. AB - The binding of the macrocycle SDM to DNA was investigated by visible spectroscopy, stopped-flow kinetics, and NMR spectroscopy. SDM is composed of two 9-aminoacridines linked via the amino groups by a spermine side chain and via the 4-positions by a N,N'-[(methylthio)ethyl]succinamide side chain [Zimmerman, S. C., Lamberson, C. R., Cory, M., & Fairley, T. A. (1989) J. Am. Chem. Soc. 111, 6805-6809]. The visible spectrum of SDM bound to poly[d(A-T)]2 or poly[d(G-C)]2 is red-shifted relative to the spectrum of SDM alone and displays considerable hypochromicity. Results from titrations of SDM with polymer indicate a binding site size of three base pairs per macrocycle. The dissociation constant for SDM bound to either poly[d(A-T)]2 or poly[d(G-C)]2 is an order of magnitude lower than that for a similar bisacridine linked only by a spermine side chain. In addition, the dependence of the dissociation constant on ionic strength is significantly reduced. NMR studies of SDM complexes with poly[d(A-T)]2 or a tetramer, d(CGCG)2, show that intercalation is the mode of binding. The magnitudes of the chemical shift differences for SDM aromatic protons in the free and bound states support intercalation with the acridine ring systems essentially parallel to the long axis of the base pairs. Cross peaks from NOESY spectra of the SDM complex with d(CGCG)2 further support this mode of binding and provide information on the structure of the complex. The results are analyzed for consistency with each of three binding models: (i) bisintercalation with the two side chains in the same groove; (ii) bisintercalation according to the neighbor exclusion principle with the two side chains in opposite grooves; and (iii) bisintercalation with two side chains in opposite grooves but with violation of the neighbor-exclusion principle. Model i is found to be unlikely on the basis of all evidence obtained, including preliminary modeling studies. Both models ii and iii can be reconciled with the experimental evidence and from a modeling standpoint are energetically feasible. PMID- 2271693 TI - Information content of amino acid residues in putative helix VIII of the lac permease from Escherichia coli. AB - Mutants in putative helix VIII of lactose permease that retain the ability to accumulate lactose were created by cassette mutagenesis. A mutagenic insert encoding amino acid residues 259-278 was synthesized chemically by using reagents contaminated with 1% each of the other three bases and ligated into a KpnI/BclI site in the lacY gene in plasmid pGEM-4. Mutants that retain transport activity were selected by transforming a strain of Escherichia coli containing a wild-type lacZ gene, but deleted in lacY, with the mutant library and identifying colonies that transport lactose on indicator plates. Sequencing of the mutated region in lacY in 129 positive colonies reveals 43 single amino acid mutations at 26 sites and 26 multiple mutations. The variable amino acid positions are largely on one side of the putative alpha-helix, a stripe opposite Glu269. This mutable stripe of low information content is probably in contact with the membrane phospholipids. PMID- 2271692 TI - Folding and unfolding of the protoxin from Bacillus thuringiensis: evidence that the toxic moiety is present in an active conformation. AB - The action of trypsin or papain on the 130-kDa crystal protein (protoxin) from Bacillus thuringiensis subsp. kurstaki HD-73 yields a 67-kDa proteinase-resistant toxic fragment (toxin) which is derived from the N-terminal half of the molecule. Sensitivity to proteolysis and fluorescence emission spectroscopy showed that the toxin unfolded to a much greater extent in 6 M guanidinium chloride (GuHCl) than in 8 M urea. Protoxin also unfolded extensively in 6 M GuHCl, whereas in 8 M urea only the C-terminal half of the molecule had unfolded extensively. Both unfolded protoxin and unfolded toxin refolded to their native and biologically active conformations. The biphasic unfolding observed for protoxin suggests that the C terminal half of the molecule unfolded rapidly, whereas the N-terminal toxic moiety unfolded at a much slower rate, similar to that of the free 67-kDa toxin. A 67-kDa fragment, derived from the N-terminal half of the molecule, could be generated from the protoxin in the presence of either urea or GuHCl by treatment with proteinases. Compared to toxin in denaturants, this fragment was found to be more sensitive to proteolysis. However, on removal of the denaturants the fragment had the same proteinase resistance and cytolytic activity as native toxin. The increased proteinase sensitivity of the fragment generated in the presence of denaturants appears to be due to a perturbation in the conformation of the N-terminal toxic moiety. This perturbation is attributed to the unfolding of the C-terminal region of the protoxin prior to its proteolysis to yield the 67 kDa fragment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271694 TI - Peptide binding to lipid bilayers. Binding isotherms and zeta-potential of a cyclic somatostatin analogue. AB - The binding of the cyclic somatostatin analogue SMS 201-995, (+)-D-Phe1-Cys2-Phe3 D-Trp4-(+)-Lys5-Thr6- Cys7-Thr(ol)8, to neutral and negatively charged lipids was investigated with a centrifugation assay and with electrophoretic and monolayer methods. Monolayers and bilayers were composed of 1-palmitoyl-2-oleoyl-sn-glycero 3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), either in pure form or in a 75/25 (mol/mol) mixture. The expansion of monolayer films demonstrated the intercalation of the peptide between the lipid molecules with a surface area requirement of 135 A2 per peptide molecule, indicating a parallel alignment of the peptide long axis with the membrane surface. Above a limiting pressure of 32.5 mN/m for POPC and 38.5 mN/m for POPG, peptide penetration was no longer possible. The peptide binding isotherm could be measured for mixed POPC/POPG bilayers up to a peptide concentration of 0.5 mM. Due to electrostatic attraction, binding between the positively charged peptide and the negatively charged membrane surface was enhanced as compared to the binding to a neutral membrane. After correction for electrostatic effects by means of the Gouy-Chapman theory, the binding isotherm as well as the electrophoretic zeta-potential measurement could be described by the same partition equilibrium with a surface partition constant of Kp = 36 +/- 4 M-1 (at 0.1 M NaCl). About 60-70% of SMS 201-995 is probably embedded in the headgroup region with little penetration into the lipid core. The partition constant increases with increasing salt concentration or with decreasing lipid lateral pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271695 TI - Sequence of the bovine 2-oxoglutarate/malate carrier protein: structural relationship to other mitochondrial transport proteins. AB - The amino acid sequence of the 2-oxoglutarate/malate carrier protein, a component of the inner membranes of mitochondria, has been deduced from the sequences of overlapping cDNA clones. These clones were generated in polymerase chain reactions using, in the first instance, complex mixtures of oligonucleotides as primers and probes, with sequences based upon partial protein sequences of cyanogen bromide fragments of the purified protein. The protein sequence of the carrier, including the initiator methionine, is 314 amino acids long. The mature protein has a modified alpha-amino group, but the nature of this modification and the precise position of the mature N-terminal amino acid have not been ascertained, although it must lie in amino acids 1-4 of the deduced protein sequence. Comparison of the protein sequence with itself and with those of 3 other mitochondrial carrier proteins, ADP/ATP translocase, the phosphate carrier, and the uncoupling protein from brown fat, shows that all 4 proteins contain a 3 fold repeated sequence about 100 amino acids in length, and all the repeats are interrelated. This suggests that the members of this family of proteins have similar structures and mechanisms and that they have evolved from a common origin. The distribution of hydrophobic amino acids in the oxoglutarate/malate carrier supports the view that the domains are folded into similar structural motifs, possibly consisting of two transmembrane alpha-helices joined by an extensive extramembranous hydrophilic region. Clones of cDNA arising from a longer related transcript of the oxoglutarate/malate carrier gene have also been analyzed. They contain 271 additional nucleotides in the 3' noncoding region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271696 TI - Mapping of the microvillar 110K-calmodulin complex (brush border myosin I). Identification of fragments containing the catalytic and F-actin-binding sites and demonstration of a calcium ion dependent conformational change. AB - In intestinal microvilli, the 110K-calmodulin complex is the major component of the cross-bridges which connect the core bundle of actin filaments to the membrane. Our previous work showed that the 110-kDa polypeptide can be divided into three functional domains: a 78-kDa fragment that contains the ATPase activity and the ATP-reversible F-actin-binding site, a 12-kDa fragment required for binding calmodulin molecules, and a terminal 20-kDa domain of unknown function [Coluccio, L. M., & Bretscher, A. (1988) J. Cell Biol. 106, 367-374]. By analysis of limited alpha-chymotryptic cleavage products, we now show that the molecular organization is very similar to that described for the S1 fragment of myosin. The catalytic site was identified by photoaffinity labeling with [5,6 3H]UTP, and fragments binding F-actin were identified by cosedimentation assays. Cleavage of the 78-kDa fragment yielded major fragments of 32 and 45 kDa, followed by cleavage of the 45-kDa fragment to a 40-kDa fragment. Of these, only the 32-kDa fragment was labeled by [5,6-3H]UTP. Physical characterization revealed that the 45- and 32-kDa fragments exist as a complex that can bind F actin, whereas the 40-kDa/32-kDa complex cannot bind actin. We conclude that the catalytic site is located in the 32-kDa fragment and the F-actin-binding site is present in the 45-kDa fragment; the ability to bind actin is lost upon further cleavage of the 45-kDa fragment to 40 kDa. Peptide sequence analysis revealed that the 45-kDa fragment lies within the molecule and suggests that the 32-kDa fragment is the amino terminus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271697 TI - Tick anticoagulant peptide: kinetic analysis of the recombinant inhibitor with blood coagulation factor Xa. AB - Tick anticoagulant peptide (TAP) is a 60 amino acid protein which is a highly specific inhibitor of human blood coagulation factor Xa (fXa) isolated from the tick Ornithodoros moubata [Waxman, L., Smith, D. E., Arcuri, K. E., & Vlasuk, G. P. (1990) Science 248, 593-596]. Due to the limited quantities of native TAP, a recombinant version of TAP produced in Saccharomyces cerevisiae was used for a detailed kinetic analysis of the inhibition interaction with human fXa. rTAP was determined to be a reversible, slow, tight-binding inhibitor of fXa, displaying a competitive type of inhibition. The binding of rTAP to fXa is stoichiometric with a dissociation constant of (1.8 +/- 0.02) x 10(-10) M, a calculated association rate constant of (2.85 +/- 0.07) x 10(6) M-1 s-1, and a dissociation rate constant of (0.554 +/- 0.178) x 10(-3) s-1. Binding studies show that 35S-rTAP binds only to fXa and not to DFP-treated fXa or zymogen factor X, which suggests the active site of fXa is required for rTAP inhibition. That rTAP is a unique serine proteinase inhibitor is suggested both by its high specificity for its target enzyme, fXa, and also by its unique structure. PMID- 2271698 TI - Participation of cob(I) alamin in the reaction catalyzed by methionine synthase from Escherichia coli: a steady-state and rapid reaction kinetic analysis. AB - The kinetic mechanism of the reaction catalyzed by cobalamin-dependent methionine synthase from Escherichia coli K12 has been investigated by both steady-state and pre-steady-state kinetic analyses. The reaction catalyzed by methionine synthase involves the transfer of a methyl group from methyltetrahydrofolate to homocysteine to generate tetrahydrofolate and methionine. The postulated reaction mechanism invokes an initial transfer of the methyl group to the enzyme to generate enzyme-bound methylcobalamin and tetrahydrofolate. Enzyme-bound methylcobalamin then donates its methyl group to homocysteine to generate methionine and cob(I)alamin. The key questions that were addressed in this study were the following: (1) Does the reaction involve a sequential or ping-pong mechanism? (2) Is enzyme-bound cob(I)alamin a kinetically competent intermediate? (3) If the reaction does involve a sequential mechanism, what is the nature of the "free" enzyme to which the substrates bind; i.e., is the prosthetic group in the cob(I)alamin or methylcobalamin state? Both the steady-state and rapid reaction studies were conducted at 25 degrees C under anaerobic conditions. Initial velocity analysis under steady-state conditions revealed a family of parallel lines suggesting either a ping-pong mechanism or an ordered sequential mechanism. Steady-state product inhibition studies provided evidence for an ordered sequential mechanism in which the first substrate to bind is methyltetrahydrofolate and the last product to be released is tetrahydrofolate. Pre-steady-state kinetic studies were then conducted to determine the rate constants for the various reactions. Enzyme-bound cob(I)alamin was shown to react very rapidly with methyltetrahydrofolate (with an observed rate constant of 250 s 1 versus a turnover number under maximal velocity conditions of 19 s-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271699 TI - Structural characterization of separated H DNA conformers. AB - Polypyrimidine/polypurine DNA sequences in plasmids can adopt protonated triplex containing structures (H DNA) in response to negative superhelical stress and low pH. A d(TC)17-d(GA)17 insert adopts two isomeric protonated structures, which differ in degree of helical unwinding. The variant forms of individual topoisomers were separated by agarose gel electrophoresis and their reactivities to permanganate and acid-induced depurination were compared. Depurination patterns of the individual conformers indicate that in the more mobile form (H y5) the 5'-half of the d(GA)n strand participates in a triplex while in the other (H-y3) the 3'-half forms the triplex. The H-y5 form is more stable than the H-y3 form at low negative superhelix densities. Because of the difference in helical unwinding, the H-y5 form becomes relatively less stable as the superhelix density increases. Topological models of the two forms show that providing there is no linkage at the tips of the triple helical segments one more positive twist is localized in the H-y5 form than in the H-y3 form. The foldback in the pyrimidine strand of the H-y5 form is less accessible to solvent than that of the H-y3 form as assessed by its lower reactivity to permanganate. Consideration of a pyrimidine loop model (Harvey, S. C., Luo, J., & Lavery, R. (1988) Nucleic Acids Res. 16, 11795-11809) suggests that the unique stability of the H-y5 form results from Watson-Crick base pairs between residues of the d(TC)n loop and the d(GA)n strand as it exits the triplex. PMID- 2271700 TI - Vitamin A metabolism in the human intestinal Caco-2 cell line. AB - The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activities, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with beta-carotene, retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271701 TI - Dipolar solvent relaxation on a nanosecond time scale in ether phospholipid membranes as determined by multifrequency phase and modulation fluorometry. AB - The present study reports on the observation of dipolar solvent relaxation in phospholipid membranes using multifrequency phase and modulation fluorometry. We measured the time-resolved emission spectra of 6-propionyl-2 (dimethylamino)naphthalene (PRODAN) in artificial bilayer membranes of chemically defined acyl-, alkyl-, and alkenyl-substituted phospholipids at 15 degrees C. 1 Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 3-O-hexadecyl-2-oleoyl-sn-glycero 1-phosphocholine, or 1-O-hexadec-1'-enyl-2-oleoyl-sn-glycero-3-phosphocholine (plasmalogen) were used as matrix lipids. The chemical structures of these lipids differ only with respect to the type of linkage (carboxyl ester, ether, or enol ether bond) between glycerol and the hydrophobic chain linked to the primary hydroxyl of glycerol. At 15 degrees C, all the lipids are in the liquid crystalline state. PRODAN probably localizes at the hydrophobic-hydrophilic interface of the phospholipid bilayer [Chong, P. L. (1988) Biochemistry 27, 399 404]. We found faster solvent relaxation of PRODAN in membranes composed of the ether lipid compared to that in the ester lipid membranes. On the other hand, the fluorescence anisotropies of the label were very similar, showing that the motion of the label itself is similar in ether and carboxyl ester lipids. We conclude that the spectral differences observed for PRODAN in ether and ester lipids could be due to different dipolar relaxation of the immediate surroundings of the label, i.e., reorientation of lipid dipoles in the glycerol region and of water molecules residing therein. PMID- 2271702 TI - Resonance Raman analysis of the Pr and Pfr forms of phytochrome. AB - Resonance Raman vibrational spectra of the Pr and Pfr forms of oat phytochrome have been obtained at room temperature. When Pr is converted to Pfr, new bands appear in the C = C and C = N stretching region at 1622, 1599, and 1552 cm-1, indicating that a major structural change of the chromophore has occurred. The Pr to Pfr conversion results in an 11 cm-1 lowering of the N-H rocking band from 1323 to 1312 cm-1. Normal mode calculations correlate this frequency drop with a Z----E isomerization about the C15 = C16 bond. A line at 803 cm-1 in Pr is replaced by an unusually intense mode at 814 cm-1 in Pfr. Calculations on model tetrapyrrole chromophores suggest that these low-wavenumber modes are hydrogen out-of-plane (HOOP) wagging vibrations of the bridging C15 methine hydrogen and that both the intensity and frequency of the C15 HOOP mode are sensitive to the geometry around the C14-C15 and C15 = C16 bonds. The large intensity of the 814 cm-1 mode in Pfr indicates that the chromophore is highly distorted from planarity around the C15 methine bridge. If the Pr----Pfr conversion does involve a C15 = C16 Z----E isomerization, then the intensity of the C15 HOOP mode in Pfr argues that the chromophore has an E,anti conformation. On the basis of a comparison with the vibrational calculations, the low frequency (803 cm-1) and the reduced intensity of the C15 HOOP mode in Pr suggest that the chromophore in Pr adopts the C15-Z,syn conformation. PMID- 2271703 TI - Two-dimensional COSY and two-dimensional NOE spectroscopy of d(AC)4.d(GT)4: extraction of structural constraints. AB - Pure absorption phase, proton two-dimensional nuclear Overhauser effect (2D NOE) and double-quantum-filtered COSY (DQF-COSY) spectra were recorded for d(AC)4.d(GT)4. A full proton resonance assignment was made, except for the 5' and 5" protons. A new semiautomatic method for improved quantitation of 2D NOE peak intensities was developed, and its limitations and usefulness were examined. With this new method, 2D NOE intensity sets at several mixing times were obtained. Simulations of the 1'2', 1'2", and 2'3' DQF-COSY cross-peaks were compared with experimental data, establishing an alternating sugar pucker for the alternating purine-pyrimidine sequence. Scalar coupling constants for the sugar ring protons, derived from the fitting of the simulated spectra, are reported. Complete relaxation matrix analysis of the 2D NOE spectrum verified this alternating structure for all NOE interactions between nonexchangeable protons. Both the DQF COSY and the 2D NOE results qualitatively indicate that the structure of d(AC)4.d(GT)4 resembles wrinkled D-DNA in aqueous solution. PMID- 2271704 TI - Solution structure studies of d(AC)4.d(GT)4 via restrained molecular dynamics simulations with NMR constraints derived from two-dimensional NOE and double quantum-filtered COSY experiments. AB - The structure of d(AC)4.d(GT)4 is investigated by constrained molecular dynamics simulations. The constraints include proton pair distances derived from 2D NOE intensities by using the iterative relaxation matrix analysis algorithm MARDIGRAS and sugar pucker phases and amplitudes derived from double-quantum-filtered COSY spectra. Molecular dynamics runs on simulated intensity and distance sets as well as the experimental data were carried out to determine the effects of starting structure, distance constraint derivation, energy functions, and experimental errors on the end result. It was found that structural details could not be elucidated within about 1.5-A overall atomic deviation. This limitation is due in part to the accuracy of the experimental data but, more importantly, is attributable to the quantity of experimental constraints available and to imperfections in the force field utilized in the molecular dynamics calculations. Within the limits of the method, some structural characteristics of d(AC)4.d(GT)4 could be elucidated. PMID- 2271705 TI - Binding of p-nitrophenyl alpha-D-galactopyranoside to lac permease of Escherichia coli. AB - Binding of the substrate analogue p-nitrophenyl alpha-D-galactopyranoside (NPG) to lac permease of Escherichia coli in different membrane preparations was investigated. Binding was assayed with an improved version of the centrifugation technique introduced by Kennedy et al. [Kennedy, E.P., Rumley, M.V., Armstrong, J.B. (1974) J. Biol. Chem. 249, 33-37]. Two binding sites for NPG were found with dissociation constants of about 16 microM and 1.6 mM at pH 7.5 and room temperature. With purified lac permease reconstituted into proteoliposomes, it could be shown that one permease molecule binds two substrate molecules. Oxidation of lac permease with the lipophilic quinone plumbagin or alkylation with the sulfhydryl reagent N-ethylmaleimide caused a 12-fold increase in the first dissociation constant. The second dissociation constant seemed to be increased as well, but its value could not reliably be estimated. Ethoxyformylation of lac permease with diethyl pyrocarbonate totally abolished NPG binding. The implications of these results for the catalytic performance of the enzyme are discussed. PMID- 2271706 TI - Arc repressor is tetrameric when bound to operator DNA. AB - The Arc repressor of bacteriophage P22 is a member of a family of DNA-binding proteins that use N-terminal residues in a beta-sheet conformation for operator recognition. Here, Arc is shown to bind to its operator site as a tetramer. When mixtures of Arc (53 residues) and an active variant of Arc (78 residues) are used in gel retardation experiments, five discrete protein-DNA complexes are observed. This result is as expected for operators bearing heterotetramers containing 4:0, 3:1, 2:2, 1:3, and 0:4 ratios of the two proteins. Direct measurements of binding stoichiometry support the conclusion that Arc binds to a single 21-base-pair operator site as a tetramer. The Arc-operator binding reaction is highly cooperative (Hill constant = 3.5) and involves at least two coupled equilibria. In the first reaction, two unfolded monomers interact to form a folded dimer (Bowie & Sauer, 1989a). Rapid dilution experiments indicate that the Arc dimer is the kinetically significant DNA-binding species and allow an estimate of the equilibrium dissociation constant for dimerization [K1 = 5 (+/- 3) x 10(-9) M]. The rate of association of Arc-operator complexes shows the expected second-order dependence on the concentration of free Arc dimers, with k2 = 2.8 (+/- 0.7) x 10(18) M-2 s-1. The dissociation of Arc-operator complexes is a first-order process with k-2 = 1.6 (+/- 0.6) x 10(-4) s-1. The ratio of these kinetic constants [K2 = 5.7 (+/- 2.3) x 10(-23) M2] provides an estimate for the equilibrium constant for dissociation of the DNA-bound tetramer to two free Arc dimers and the operator. An independent determination of this complex equilibrium constant [K2 = 7.8 (+/- 4.8) x 10(-23) M2] was obtained from equilibrium binding experiments. PMID- 2271707 TI - Nucleotide sequence of the gene for the b subunit of human factor XIII. AB - Factor XIII (Mr 320,000) is a blood coagulation factor that stabilizes and strengthens the fibrin clot. It circulates in blood as a tetramer composed of two a subunits (Mr 75,000 each) and two b subunits (Mr 80,000 each). The b subunit consists of 641 amino acids and includes 10 tandem repeats of 60 amino acids known as GP-I structures, short consensus repeats (SCR), or sushi domains. In the present study, the human gene for the b subunit has been isolated from three different genomic libraries prepared in lambda phage. Fifteen independent phage with inserts coding for the entire gene were isolated and characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene was found to be 28 kilobases in length and consisted of 12 exons (I-XII) separated by 11 intervening sequences. The leader sequence was encoded by exon I, while the carbonyl-terminal region of the protein was encoded by exon XII. Exons II-XI each coded for a single sushi domain, suggesting that the gene evolved through exon shuffling and duplication. The 12 exons in the gene ranged in size from 64 to 222 base pairs, while the introns ranged in size from 87 to 9970 nucleotides and made up 92% of the gene. The introns contained four Alu repetitive sequences, one each in introns A, E, I, and J. A fifth Alu repeat was present in the flanking 3' end of the gene. Two partial KpnI repeats were also found in the introns, including one in intron I and one in intron J. The KpnI repeat in intron J was 89% homologous to a sequence of approximately 2200 nucleotides flanking the gene coding for human beta globin and approximately 3800 nucleotides from the L1 insertion present in the gene for human factor VIII. Intron H also contained an "O" family repeat, while two potential regions for Z-DNA were identified within introns G and J. One nucleotide change was found in the coding region of the gene when its sequence was compared to that of the cDNA. This difference, however, did not result in a change in the amino acid sequence of the protein. PMID- 2271708 TI - Effect of unsaturated phosphatidylethanolamine on the chain order profile of bilayers at the onset of the hexagonal phase transition. A 2H NMR study. AB - The quadrupolar splitting profiles of methylene groups along the acyl chains of perdeuteriated dimyristoylphosphatidylcholine (DMPC-d54) in mixtures with dioleoylphosphatidylethanolamine (DOPE) were studied by 2H NMR. The quadrupolar splittings, obtained for lipid mixtures in the bilayer state, were measured as functions of temperature and PE:PC ratio and were used to obtain the approximate gauche probabilities at a given chain position, pB. Ratios (R) of pB for C13, C12, and C11 relative to that of the plateau region were used to characterize the effect of increasing PE on the gauche content of PC chains. At all temperatures studied (including the bilayer to hexagonal phase transition region), for each ratio R (e.g., RC13/P), the relative gauche content of the DMPC chains was similar over the range of 25-85% PE. DOPE is viewed in simple terms as having a "conical" shape; if this geometry applies to the acyl chain region of the molecule, a greater lateral pressure would be expected toward the center of the bilayer as the PE content is increased, resulting in a decreased gauche content, relative to the plateau, of those methylene groups of PC. The failure to observe the predicted increase in lateral pressure has ramifications for the cone-shape molecular model. The overall "cone shape" of PE is seen to arise from the smaller size of the head-group relative to the acyl chains; however, the acyl chain region itself is not rigidly cone-shaped and is better represented by a flexible "balloon". These results were supported by small-angle X-ray diffraction, which showed a decreasing trend in the area per molecule with increasing PE content. PMID- 2271709 TI - Crystal structure of the aspartic acid-199----asparagine mutant of chloramphenicol acetyltransferase to 2.35-A resolution: structural consequences of disruption of a buried salt bridge. AB - The crystal structure of the Asp-199----Asn mutant of chloramphenicol acetyltransferase (CAT) has been determined to 2.35-A resolution. In wild-type CAT Asp-199 is involved in a fully buried intrasubunit salt bridge with Arg-18, an interaction that is adjacent to the active site. Replacement of aspartate with asparagine by site-directed mutagenesis disrupts this salt bridge and causes extensive conformational changes within the active site. The imidazole group of the catalytically essential His-195 is reoriented, with the loss of interactions thought to stabilize the preferred tautomer of this residue. Arg-18 and Asn-199 form three new intersubunit interactions as a result of large side-chain torsion angle changes which cause the movement of two polypeptide loops, some residues of which are up to 20 A away from the site of the mutation. The new interactions of Arg-18 and Asn-199 compensate for the loss of the buried salt bridge and afford near-wild-type thermostability to Asn-199 CAT, albeit with a greatly reduced activity. PMID- 2271710 TI - Affinity labeling of aminoacyl-tRNA synthetases with adenosine triphosphopyridoxal: probing the Lys-Met-Ser-Lys-Ser signature sequence as the ATP-binding site in Escherichia coli methionyl-and valyl-tRNA synthetases. AB - Pyridoxal 5'-triphospho-5'-adenosine (AP3-PL), the affinity labeling reagent specific for lysine residues in the nucleotide-binding site of several enzymes [Tagaya, M., & Fukui, T. (1986) Biochemistry 25, 2958-2964; Yagami, T., Tagaya, M., & Fukui, T. (1988) FEBS Lett. 229, 261-264], was used to identify the ATP binding site of Escherichia coli methionyl-tRNA synthetase (MetRS). Incubation of this enzyme with AP3-PL followed by reduction with sodium borohydride resulted in a rapid inactivation of both the tRNA(Met) aminoacylation and the methionine dependent ATP-PPi exchange activities. Complete inactivation corresponded to the incorporation of 0.98 mol of AP3-PL/mol of monomeric trypsin-modified MetRS. ATP or MgATP protected the enzyme from inactivation. The labeling with AP3-PL was also applied to E. coli valyl-tRNA synthetase (ValRS). Both the tRNA(Val) aminoacylation and the valine-dependent ATP-PPi exchange activities were abolished by the incorporation of 0.91 mol of AP3-PL/mol of monomeric ValRS. AP3 PL was found attached to lysine residues 335, 402, and 528 in the primary structure of MetRS. In the case of ValRS, the AP3-PL-labeled residues corresponded to lysines 557, 593, and 909. We therefore conclude that these lysines of MetRS and ValRS are directed toward the ATP-binding site of these synthetases, more specifically at or close to the subsite for the gamma-phosphate of ATP. AP3-PL-labeled Lys-335 of MetRS and Lys-557 of ValRS belong to the consensus tRNA CCA-binding Lys-Met-Ser-Lys-Ser sequence [Hountondji, C., Dessen, P., & Blanquet, S. (1986) Biochimie 68, 1071-1078].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271711 TI - Affinity cleavage and targeted catalysis of proteins using the avidin-biotin system. AB - The avidin-biotin system was used in order to target enzymes to their substrates in complex mixtures of proteins in solution. The approach described here thus mimics natural systems in which enzymes usually act in selective fashion, due, perhaps, to proximity effects. For affinity cleavage studies, biotinyl transferrin was used as a model target substrate. Avidin or streptavidin was then employed to bridge between the biotinylated target protein and a biotinyl protease. Bovine serum albumin was included in the reaction mixtures to assess the level of nonspecific cleavage. In the case of an unbiotinylated target protein, avidin could be used to inhibit the hydrolytic action of the biotinyl protease. In some systems, a biotinyl antibody could be used to direct the avidin bridged biotinyl protease to an unbiotinylated target antigen. The data support the contention that preferential cleavage reflects two separate phenomena: (i) avidin confers a conformational alteration of the biotinylated target protein, and (ii) the biotinyl protease is targeted (via the avidin bridge) to the proximity of the biotinylated target protein, thereby promoting cleavage of the conformationally altered molecule. This is the first report in which a proteolytic enzyme could be selectively targeted to specifically hydrolyze a defined protein substrate in solutions containing a complex mixture of other proteins. The approach appears to be a general phenomenon for "targeted catalysis", appropriate for other applications, particularly for affinity cleavage and targeted catalysis of cell-based macromolecules. PMID- 2271713 TI - Praying for peace. PMID- 2271712 TI - Catalytic activities of human liver cytochrome P-450 IIIA4 expressed in Saccharomyces cerevisiae. AB - A human liver cytochrome P-450 (P-450) IIIA4 cDNA clone was inserted behind an alcohol dehydrogenase promoter in the plasmid vector pAAH5 and expressed in Saccharomyces cerevisiae (D12 and AH22 strains). A cytochrome P-450 with typical spectral properties was expressed at a level of approximately 8 x 10(5) molecules/cell in either strain of yeast. The expressed P-450 IIIA4 had the same apparent monomeric Mr as the corresponding protein in human liver microsomes (P 450NF) and could be isolated from yeast microsomes. Catalytic activity of the yeast microsomes toward putative P-450 IIIA4 substrates was seen in the reactions supported by cumene hydroperoxide but was often lower and variable when supported by the physiological donor NADPH. The catalytic activity of purified P-450 IIIA4 was also poor in some systems reconstituted with rabbit liver NADPH-P-450 reductase and best when both the detergent 3-[(3-cholamidopropyl)dimethylammonio] 1-propanesulfonate and a lipid extract (from liver or yeast microsomes) or L alpha-1,2-dilauroyl-sn-glycero-3-phosphocholine were present. Under these conditions the expressed P-450 IIIA4 was an efficient catalyst for nifedipine oxidation, 6 beta-hydroxylation of testosterone and cortisol, 2-hydroxylation of 17 beta-estradiol and 17 alpha-ethynylestradiol, N-oxygenation and 3 hydroxylation of quinidine, 16 alpha-hydroxylation of dehydroepiandrosterone 3 sulfate, erythromycin N-demethylation, the 10-hydroxylation of (R)-warfarin, the formation of 9,10-dehydrowarfarin from (S)-warfarin, and the activation of aflatoxins B1 and G1, sterigmatocystin, 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (both + and - diastereomers), 3,4-dihydroxy-3,4-dihydrobenz[a]anthracene, 3,4 dihydroxy-3,4-dihydro-7, 12-dimethylbenz[a]anthracene, 9,10-dihydroxy-9,10 dihydrobenzo[b]fluoranthene, 6-aminochrysene, and tris(2,3-dibromopropyl) phosphate to products genotoxic in a Salmonella typhimurium TA1535/pSK1002 system where a chimeric umuC' 'lacZ plasmid is responsive to DNA alkylation. Reaction rates were stimulated by 7,8-benzoflavone and inhibited by rabbit anti-P-450 IIIA (anti-P-450NF), troleandomycin, gestodene, and cimetidine. Evidence was obtained that rates of reduction of ferric P-450 IIIA4 in yeast microsomes and the reconstituted systems are slow and at least partially responsible for the lower rates of catalysis seen in these systems (relative to liver microsomes). The results of these studies with a defined protein clearly demonstrate the ability of P-450 IIIA4 to catalyze regio- and stereoselective oxidations with a diverse group of substrates, and this enzyme appears to be one of the most versatile catalysts in the P-450 family. PMID- 2271714 TI - Cardiac and respiratory responses to esophageal dilatation during REM sleep in human infants. AB - Forty-one preterm and fullterm infants (26.5-40.5 weeks gestational age and 31.5 50 weeks postconceptional age) free from neurologic and cardiopulmonary disease at the time of testing underwent a standardized esophageal dilatation test (EDT) during polygraphically controlled REM sleep. RR interval and total duration of the respiratory cycle (TTOT) were measured (1) during the 60 s preceding the EDT, i.e. mean control RR and mean control TTOT; (2) during EDT. Percent RR (%RR) was defined as the longest RR interval in milliseconds during EDT divided by mean control RR in milliseconds multiplied by 100, and percent TTOT (%TTOT) as the longest TTOT in seconds during EDT divided by mean control TTOT in seconds multiplied by 100. EDT provoked prolongation of both RR interval and TTOT. %RR decreased significantly with advancing gestational age (p less than 0.003), and %TTOT with advancing postconceptional age (p less than 0.003), indicating that both cardiac and respiratory responses to an EDT challenge are blunted with maturation. PMID- 2271715 TI - Hypersomatotropism in the dysmature infant at term and preterm birth. AB - Growth hormone (GH) concentrations were measured in cord serum of small (less than 2.4 kg), appropriate (3.4 +/- 0.1 kg) and large (greater than 4.4 kg) infants born at term (38-42 weeks), and in cord serum of prematurely born twins (28-36 weeks) which were either appropriate (greater than P10) or small (less than P10) for gestational age. Cord serum GH levels were found to be significantly elevated in small for gestational age infants, both at term and preterm birth. In view of the insulin-antagonizing action of fetal GH, these results further support a homeostatic function for GH in the late-gestational human fetus. PMID- 2271716 TI - Regional circulatory responses to hindlimb work in developing swine. AB - Circulatory effects of hindlimb work were studied in 29 swine (aged 1 day to 1 month) anesthetized with pentobarbital. Femoral, renal and intestinal blood flow, resistance and autoregulatory capability were determined at different levels of hindlimb oxygen consumption before and during distal sciatic nerve stimulation. Increases in oxygen consumption were accompanied by hyperemia at all ages, but by increased oxygen extraction only in 2-week and 1-month-old animals, without evidence of autoregulation. Blood flow was consistently redistributed from the kidney and small intestine only in neonates. Older animals generally sustained autoregulation of renal and intestinal blood flows throughout experiments. We concluded that hindlimb work evokes age-related adjustments in regional blood flow that reflect the balance of neural and autoregulatory control. PMID- 2271717 TI - Plasma cortisol distribution in the pig from birth to six weeks of age. AB - Plasma levels of cortisol and percent distribution of cortisol among protein bound (corticosteroid-binding globulin (CBG) and albumin) and unbound forms were measured in naturally born/conventionally reared pigs from birth to 6 weeks of age. Total cortisol and percent unbound cortisol were highest in pigs at birth and decreased (p less than 0.01) in a linear fashion over the sampling period. Percent CBG-bound cortisol was lowest on days 3-21 relative to the peak value seen on day 42. However, actual CBG-bound cortisol was not different after day 1. Percent albumin-bound cortisol was highly correlated with percent CBG-bound cortisol (r = -0.90; p less than 0.001). These results suggest that a rapid shift in cortisol distribution from unbound and albumin-bound forms to that which is bound to CBG occurs by approximately day 28 of age in the neonatal pig. PMID- 2271718 TI - Umbilical cord separation: histological findings and perinatal factors. AB - The aim of this study was to investigate if perinatal factors influenced the histology of the umbilical area of neonates who died when umbilical cord separation was occurring or had just been completed. It was found that the older the infant was at death the greater the degree of infiltration of polymorphonuclear leucocytes into the area of separation of the umbilical cord. The infiltration was less when the infant was delivered by caesarean section than when the infant was delivered vaginally. The other factors studied (sex, birth weight, gestational age, positive blood culture, time of rupture of the membranes) did not influence the histological findings. PMID- 2271719 TI - Synchronization of the seminiferous epithelium after vitamin A replacement in vitamin A-deficient mice. AB - The effect of vitamin A deficiency and vitamin A replacement on spermatogenesis was studied in mice. Breeding pairs of Cpb-N mice were given a vitamin A deficient diet for at least 4 wk. The born male mice received the same diet and developed signs of vitamin A deficiency at the age of 14-16 wk. At that time, only Sertoli cells and A spermatogonia were present in the seminiferous epithelium. These spermatogonia were topographically arranged as single and paired cells and as clones of 4, 8 and more cells. A few mitoses of single, paired, and clones of 4 A spermatogonia were found, which were randomly distributed over the seminiferous epithelium. When vitamin A-deficient mice were treated with retinol-acetate combined with a normal vitamin A-containing diet, spermatogenesis restarted again synchronously. Only a few successive stages of the cycle of the seminiferous epithelium were present up to at least 43 days after vitamin A replacement. After 20 days, 98.3% of the seminiferous tubules were synchronized, showing pachytene spermatocytes as the most advanced cell type, mostly being in epithelium stages IX-XII. After 35 and 43 days, spermatogenesis was complete in 99.6% of the tubular cross sections, and most tubular cross sections were in stages IV-VII of the cycle of the seminiferous epithelium. The degree of synchronization was comparable or even higher than found in rats. The rate of development of the spermatogenic cells between 8 and 43 days after vitamin A replacement seemed to be similar to that in normal mice. Assuming that the rate of development of the spermatogenic cells is also normal during the first 8 days after vitamin A replacement, it can be deduced that the preleptotene spermatocytes, present after 8 days, were A spermatogonia in the beginning of stage VIII at the moment of vitamin A replacement. These results indicate that the mouse can be used as a model to study epithelial stage dependent processes in the testis. PMID- 2271720 TI - Reversible inhibition of fertility in mice by passive immunization with anticumulus oophorus antibodies. AB - The mucified cumulus oophorus represents an outer enveloping layer around ovulated mammalian oocytes. This coat in its definitive expanded form appears late in the preovulatory development as a result of intensive secretion of intercellular matrix by cumulus cells. We have shown recently that antibodies to the cumulus matrix inhibit human fertilization in vitro. This study was undertaken to assess, in an animal model, the effects of anticumulus oophorus antibodies on fertility by use of different passive immunization protocols. A purified anticumulus immunoglobulin fraction was prepared from hyperimmune rabbit serum and administered at different times before and after mating to mice superovulated with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). A dose-dependent negative effect of this anticumulus antibody preparation on the number of fertilized eggs recovered from the oviducts of treated animals was observed when the antibodies were given before mating. High antibody doses also interfered with oocyte maturation and ovulation if applied on the day of eCG treatment, but no effects on these processes were found when the antibodies were given on the day of hCG treatment. The antifertility effect of anticumulus antibodies was reversible and the antibodies did not affect postfertilization development. These findings make cumulus oophorus antigens serious candidates for the development of a contraceptive vaccine. PMID- 2271721 TI - Changes and localization of ovarian carbonyl reductase during pseudopregnancy and pregnancy in rats. AB - The present study investigates changes in the activity and enzyme content of ovarian carbonyl reductase (CR), which catalyzes the reduction of 9-keto and 15 ketoprostaglandins in rats during pseudopregnancy and pregnancy. The activity of ovarian CR decreased from the onset of pseudopregnancy and pregnancy, reaching 20 30% of the Day 1 value by Day 12 of pseudopregnancy and 50-60% of the Day 1 value by Day 14 of pregnancy. In the case of pregnant rats, the enzyme activity maintained a minimal level between Day 14 of pregnancy and Day 22 of parturition. An acute increase of the enzyme activity was found on the morning after parturition. The CR content in the ovary maintained a constant level from Day 1 to Day 12 of pseudopregnancy and to Day 18 of pregnancy. In pregnant rats, there was a gradual decrease after 18 days and then a surge during parturition. CR was primarily localized in interstitial gland cells and in theca interna cells but was not found in corpora lutea cells in the ovary during the estrous cycle. Additional immunostaining was also observed in corpora lutea cells during pseudopregnancy and pregnancy. The changes in ovarian CR activity, i.e. the rapid decrease with progressing pseudopregnancy and pregnancy, correlated with the increase in progesterone and the decrease in LH. These results indicate that rat ovarian CR may be regulated via the hypothalamo-pituitary-ovarian axis and may also be involved in luteal function. PMID- 2271722 TI - Intraluminal androgen binding protein alters 3H-androgen uptake by rat epididymal tubules in vitro. AB - Previous experiments have shown that androgen binding protein (ABP) and androgens exist in high concentrations in the tissue and the lumen of the rat caput epididymis. The present experiments were performed to determine whether or not intraluminal APB affects tubule net uptake of androgens. Caput epididymal tubules were dissected into 2-cm segments, subjected to microperfusion into the tubule lumen, and incubated for 2.5 h in 35 degrees C minimum essential medium (MEM) containing 2.0 ng tritiated testosterone (3H-T) per ml. 14C-polytheylene glycol [PEG] was included as a contamination marker. In the first series of experiments, caput tubules were perfused with a control, artificial perfusion (MKB) containing no ABP or fresh rat rete testis fluid (RTF), which is known to contain ABP. Tubules incubated while containing RTF took up 138% of the tritiated androgens taken up by control tubules. In the second series of experiments, tubules were perfused with fresh caput epididymal lumen content, MKB alone, MKB containing either 5.0 ng purified rat ABP/microliters or 50 ng ABP/microliters. Tubules incubated while containing perfused MKB took up only 47% of the tritiated androgens taken up by tubules containing perfused native lumen content. Increasing intraluminal ABP concentrations in the MKB medium increased 3H androgen uptake in a stepwise fashion. Intraluminal ABP at a concentration of 50 ng/microliters was associated with a 71% return of 3H-androgen uptake towards that amount of 3H-androgen taken up by tubules perfused with native lumen content. Intraluminal ABP enhances net androgen uptake by caput epididymal tubules from their surrounding medium in vitro. PMID- 2271723 TI - Stimulation of parthenogenesis in mouse ovarian follicles by inhibitors of inosine monophosphate dehydrogenase. AB - The effects of hormonal priming and inosine monophosphate (IMP) dehydrogenase inhibitors on the meiotic maturation and parthenogenetic activation of mouse oocytes were examined in this study. In the first series of experiments, unprimed mice or mice primed 24 h with equine chorionic gonadotropin (eCG) received injections of the IMP dehydrogenase inhibitors, bredinin (Br) or mycophenolic acid (MA), followed by histological examination at 24 h, 48 h, and 72 h after drug administration. In both treatment groups, oocytes from nonatretic antral follicles were stimulated to undergo germinal vesicle breakdown by 24 h and became parthenogenetically activated as manifested by pronuclear formation and early cleavage divisions. The parthenotes underwent degeneration by 72 h. In the second part of this study, the effects of priming and drug treatment on parthenogenetic activation and subsequent developmental potential in vitro were examined. Mice were primed with eCG, and 24 or 48 h later received injections of Br or MA. Cumulus cell-enclosed oocytes were isolated 21-22 h later and assessed for maturation; those having undergone germinal vesicle breakdown were cultured and subsequently examined for embryonic development. In mice primed for 24 h, but not 48 h, Br and MA stimulated a significant number of oocytes to resume maturation in vivo; these subsequently underwent activation and developed to blastocysts in vitro. In another series of experiments, germinal vesicle-stage oocytes were isolated from primed or unprimed mice and cultured in vitro to permit spontaneous meiotic maturation. Nine percent of mature ova from 24-h primed mice developed to 2-cell parthenotes; activation in ova from unprimed and 48-h-primed mice was considerably lower. A time-course experiment demonstrated that the extent of parthenogenetic activation in vivo following Br treatment was related to the period of time between drug injection and isolation of ova, the optimal period being 12 h. Neither Br nor MA had a direct activating effect on the oocytes as evidenced by an inability to induce parthenogenesis in vitro. Simultaneous injection of hCG with either Br or MA stimulated ovulation and prevented the parthenogenetic response. These data are consistent with the idea that conditions within the follicle promote parthenogenetic activation when the oocyte matures in the absence of gonadotropin stimulation. PMID- 2271724 TI - Effects of progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of nidation, and termination of pregnancy in bonnet monkeys. AB - The effects of a progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of implantation or pregnancy, and termination of early and mid-pregnancy were studied in bonnet monkeys. In the regularly menstruating animals, administration of lilopristone (25 mg/day, s.c.) during the mid-luteal phase (Days 20-22 of the menstrual cycle) induced menstruation within 2-4 days after the initiation of treatment. A premature drop in circulating progesterone levels was also observed. The luteolytic effect of lilopristone was prevented by exogenous treatment with hCG; however, the animals showed premature menstruation, in spite of high progesterone levels (above 4 ng/ml). Treatment around the time of implantation (between Days 8 and 12 after the mid-cycle peak in estradiol levels) in mated animals provided 100% pregnancy protection. Treatment of pregnant animals on Days 30-32 of the menstrual cycle, i.e. about Day 20 after the estradiol peak, induced abortion in 8 of 10 animals. A significant (p less than 0.05) decrease in serum progesterone levels was observed on Day 3 after the initiation of treatment. However, the decrease was slower (slope: -0.36, r: 0.96) compared to that observed in nonpregnant animals (slope: 0.72, r: 0.95). In the other two animals, pregnancy was not affected. However, when the treatment was delayed until about Day 50 after the estradiol peak, all four animals aborted. This study suggests that lilopristone is a progesterone antagonist with a potential to induce menstruation, inhibit nidation, and terminate pregnancy. The antifertility effects are mediated through blocking progesterone action at the endometrium as well as decreasing progesterone bioavailability, which appears to be due to its effects on gonadotropin release. PMID- 2271725 TI - Regulation of luteinizing hormone secretion in prepubertal heifers fed an energy deficient diet. AB - The effects of feeding a diet restricted in energy on the endocrine mechanisms regulating LH secretion in prepubertal heifers were examined. On Day 0, thirty heifers were assigned to be either ovariectomized (OVX; n = 10), ovariectomized and administered an estradiol implant (OVXE; n = 10), or to remain ovary-intact (INT, n = 10). Five heifers each were then assigned to be fed either a control (C) or a two-phase, low-to-high energy (L), dietary treatment. The C diet was formulated to support weight gains of 1.1 kg/day throughout the experiment (Day 0 197). Heifers receiving the L treatment were provided a diet restricted in energy (33% of C diet) from Day 0-127 followed by a diet similar to that fed to heifers receiving the C treatment from Day 128-197. Secretion of LH increased rapidly following ovariectomy in C-OVX and L-OVX heifers. During the period of energy restriction, LH pulse frequency was reduced, and mean LH concentration, pulse amplitude, and pituitary response to LHRH were greater in L-OVX than in C-OVX heifers. In L-OVXE and L-INT heifers, secretion of LH was low and unchanged during the period of dietary energy restriction. In contemporaneous treatment groups fed the C diet (C-OVXE and C-INT), frequency of LH pulses increased gradually during this period and C-INT heifers attained puberty on Day 121 +/- 18. Upon switching heifers in the L-OVX, L-OVXE, and L-INT treatments to the C diet, all characteristics of LH secretion changed markedly within 14 days to levels similar to those detected in the C treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271726 TI - Identification and characterization of bovine oviductal glycoproteins synthesized at estrus. AB - Published reports indicate that in several mammalian species the oviduct synthesizes and secretes specific glycoproteins which are components of the luminal fluids at the time of ovulation and fertilization. The present study characterized the secretory glycoproteins synthesized by the bovine oviduct at estrus. Oviducts obtained from four crossbred cows in estrus were flushed with saline, and segments of the ampullary and isthmic regions were fixed for immunocytochemical analyses. The remainder of the tissue was subjected to explant culture for 24 h in medium containing either 3H-leucine or 3H-glucosamine. Analysis of culture media by one- and two-dimensional SDS-PAGE followed by fluorography indicated that both the ampullary and isthmic regions synthesized a major class of Mr 97,000 glycoproteins with isoelectric points ranging from 5.5 to 8.1. A polyclonal antibody was generated to the glycoproteins after their isolation by gel filtration followed by electrophoretic separation. Western blot analysis of oviductal culture media indicated that the antisera cross-reacted with a doublet at Mr 97,000 and to a lesser extent with two additional bands at Mr greater than 200,000. Immunoreactive antigens were not identified in serum or in culture media of ovary, uterus, and nonreproductive tract tissues. The Mr 97,000 glycoproteins were present in oviductal flushings obtained from cows in estrus. They were also detected to a lesser degree in oviductal flushings obtained from cows at Days 5, 10, 15, and 18 of the estrous cycle, with the least amount of immunoreactivity being observed in Day 10 samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271727 TI - Flumethason-induced calving is preceded by a period of myometrial inhibition during luteolysis. AB - The temporal relationship among changes of the concentrations of the 13,14 dihydro-15-keto metabolite of prostaglandin F2 alpha (PGFM), estrone (E1) and estrone sulphate (E1S) in maternal arterial plasma (MP) and amniotic fluid (AF), the prepartum progesterone (P4) decline in MP, and the evolution of uterine electromyographic (EMG) activity was investigated in 6 cows. Calving was induced by a single i.m. injection of 5 mg flumethason on Day 270 of gestation. The period under investigation was subdivided into four consecutive periods: Period 1 covered the last 2 days before flumethason treatment; Period 2 (mean +/- SEM duration: 16.1 +/- 2.5 h), Period 3 (8.8 +/- 1.1 h), and Period 4 (13.0 +/- 1.5 h) together included the interval between injection and the onset of the expulsive stage of induced parturition. Each was defined by its pattern of uterine EMG activity. During Periods 1 and 2, this activity occurred in long episodes (2-20 min; contractures) at a similar mean (+/- SEM) frequency (0.51 +/- 0.14/h and 0.42 +/- 0.07/h, respectively). No significant differences in hormonal concentrations in MP and AF between these two periods were detected. During Period 3, contractures nearly disappeared (freq: 0.09 +/- 0.05/h), and in MP mean P4 levels were significantly lower and PGFM levels were significantly higher than before. Mean PGFM concentrations in AF were not significantly changed during Period 3. Finally, during Period 4, EMG activity reappeared and a parturient EMG pattern gradually evolved in the presence of a further significant decline of P4 levels and significant increase of PGFM concentrations in MP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271728 TI - Ovarian reproductive function after exposure to diethylstilbestrol in neonatal life. AB - Inbred and random-bred NMRI mice were treated with diethylstilbestrol (DES, 5 micrograms per day) or vehicle (olive oil) on Days 1-5 after birth. At the age of 8 wk, females were treated with saline or eCG and hCG to induce ovulation. Ova never occurred in the ampulla of the uterine tube of saline-treated, DES-treated females when these mice were not mated. After gonadotropin treatment, ova were found in the ampulla of all olive oil-treated females and in approximately 80% of DES-treated females. The number of ovulated ova was similar in both groups. Twenty percent of gonadotropin-treated, DES-treated females had ova in the ampulla and a vaginal plug after being caged with males but none became pregnant. Ovaries from inbred control or DES-treated females were grafted to the ovarian bursa of control or DES-treated ovariectomized hosts. DES-treated hosts, carrying control or DES-exposed ovaries, never became pregnant. Control females, with control ovaries or DES-exposed ovaries, became pregnant; pregnancy rate and litter size were similar for control mice regardless of whether they were supporting DES-exposed or control ovaries. Oocytes from ovaries exposed neonatally to DES can thus give rise to apparently normal offspring. The results also indicate DES-induced nonovarian disturbances, e.g. tubal and/or endometrial function, both of which are important for fertility. In the grafting experiments, a high mortality rate was found in inbred DES-exposed females caged with males. All deaths were associated with vaginal concrements (vaginal stones) and intestinal complications. PMID- 2271729 TI - Polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol in vivo and in vitro. AB - In 35-day-old C57BL/Tw female mice given daily injections of 1 microgram diethylstilbestrol (DES) for 5 days from the day of birth, a significantly higher incidence of polyovular follicles (PF) were found in the ovaries than in those of age-matched control mice. Ovaries of prepubertal mice treated neonatally with oil or DES (DES mice) showed an enhancement of ovulation and luteinization following a combined treatment with eCG and hCG. Tubal ova in DES mice treated with eCG plus hCG were surrounded by many granulosa cells. Incidence of PF in control mice was not changed by eCG plus hCG treatment. In contrast, PF incidence in DES mice was reduced by prepubertal injections of eCG plus hCG. A high incidence of PF was also found in newborn mouse ovaries transplanted for 30 days into ovariectomized adult hosts given DES injections, but not in ovaries transplanted into intact or ovariectomized DES-untreated hosts. When neonatal ovaries were cultivated in a serum-free medium containing DES for 5 days and then transplanted into ovariectomized hosts, PF were formed in the grafts, but not in DES-unexposed grafts. Oocytes from PF in DES mice were found to have a smaller capacity for fertilization when examined in vitro. The present study also demonstrated that neonatal ovaries exposed to estrogen in vivo or in vitro (which produces PF in prepubertal hosts) are capable of responding to gonadotropins given later, resulting in a reduction of PF incidence, and that exogenous estrogen acts directly on neonatal ovaries to induce PF. PMID- 2271730 TI - Dense fibers protect mammalian sperm against damage. AB - The relative tensile strengths of the sperm of seven mammalian species and sea urchins have been measured by determining the minimum shear necessary to kill them (assayed by lack of motility) when they are suspended in a viscous fluid. In general, long sperm are killed by smaller shears than short sperm. However, the longer sperm are not as fragile as would be expected from theoretical predictions. Their additional tensile strength correlates well with the size of their dense fibers; a theory that includes the dense fiber contributions accurately predicts the sperm tensile strength for most of the species in which this has been measured. This added strength may be necessary to protect sperm from shear forces encountered during epididymal transport and especially during ejaculation, as these forces are strong enough to kill long sperm if they are not strengthened. PMID- 2271731 TI - An improved method of purifying inhibin radioligand for radioimmunoassay. AB - Polyacrylamide gel electrophoresis (PAGE) separation of bovine inhibin from free iodine after iodination is described. Previous methods of separation typically relied upon a G25 gel filtration and Matrix gel Red A affinity column chromatography protocol. When compared to column chromatography, PAGE-purified radiolabelled inhibin resulted in significantly increased binding (13.1% vs. 7.5%) and enhanced sensitivity (ED50 = 92 microliters inhibin standard vs. ED50 = 198 microliters inhibin standard) to the inhibin antibody #1989. Our results demonstrate an advantageous approach to purifying 31,000 Mr bovine inhibin radioligand after iodination for RIA. PMID- 2271732 TI - Intraluteal infusions of prostaglandins of the E, D, I, and A series prevent PGF2 alpha-induced, but not spontaneous, luteal regression in rhesus monkeys. AB - A luteotropic role for prostaglandins (PGs) during the luteal phase of the menstrual cycle of rhesus monkeys was suggested by the observation that intraluteal infusion of a PG synthesis inhibitor caused premature luteolysis. This study was designed to identify PGs that promote luteal function in primates. First, the effects of various PGs on progesterone (P) production by macaque luteal cells were examined in vitro. Collagenase-dispersed luteal cells from midluteal phase of the menstrual cycle (Day 6-7 after the estimated surge of LH, n = 3) were incubated with 0-5,000 ng/ml PGE2, PGD, 6 beta PGI1 (a stable analogue of PGI2), PGA2, or PGF2 alpha alone or with hCG (100 ng/ml). PGE2, PGD2, and 6 beta PGI1 alone stimulated (p less than 0.05) P production to a similar extent (2- to 3-fold over basal) as hCG alone, whereas PGA2 and PGF2 alpha alone had no effect on P production. Stimulation (p less than 0.05) of P synthesis by PGE2, PGD2, and 6 beta PGI1 in combination with hCG was similar to that of hCG alone. Whereas PGA2 inhibited gonadotropin-induced P production (p less than 0.05), that in the presence of PGF2 alpha plus hCG tended (p = 0.05) to remain elevated. Second, the effects of various PGs on P production during chronic infusion into the CL were studied in vivo. Saline with or without 0.1% BSA (n = 12), PGE2 (300 ng/h; n = 4), PGD2 (300 ng/h; n = 4), 6 beta PGI1 (500 ng/h; n = 3), PGA2 (300 ng/h; n = 4), or PGF2 alpha (10 ng/h; n = 8) was infused via osmotic minipump beginning at midluteal phase (Days 5-8 after the estimated LH surge) until menses. In addition, the same dose of PGE, PGD, PGI, or PGA was infused in combination with PGF2 alpha (n = 3-4/group) for 7 days. P levels over 5 days preceding treatment were not different among groups. In 5 of 8 monkeys receiving PGF2 alpha alone, P declined to less than 0.5 ng/ml within 72 h after initiation of infusion and was lower (p less than 0.05) than controls. The length of the luteal phase in PGF2 alpha-infused monkeys was shortened (12.3 +/- 0.9 days; mean +/- SEM, n = 8; p less than 0.05) compared to controls (15.8 +/- 0.5). Intraluteal infusion of PGE, PGD, PGI, or PGA alone did not affect patterns of circulating P or luteal phase length.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271733 TI - Frequency of the stages in the cycle of the seminiferous epithelium in the rat. AB - This study determined the optimum number of tubules to be counted per testis cross section, and the number of animals per treatment group, when changes in stage frequencies in the cycle of the seminiferous epithelium are criteria for assessing effects of treatment on spermatogenesis. A data base of 9,672 observed and staged tubules was collected from testicular cross sections of 15 Sprague Dawley rats. A significant variation between animals was found for the frequencies of Stages I, II, IV, VI, VIII, and XIII. Computer simulation was used to randomly select different combinations of animal and tubule numbers from the observed data. Stage frequency means from each simulation experiment were compared statistically to observed mean frequencies. A model that used data from all 14 stages was analyzed. The following conclusions were made: a) a minimum of 200 tubule cross sections/testis is recommended for estimating stage frequencies; b) for a fixed number of tubules scored, the number of animals sampled is more important than the number of tubules per animal in reducing variance; c) to detect a difference of 2 standard deviations from the mean with a 2% error rate and examining 200 tubules/testis, at least 12 animals must be used per group when assessing all 14 stages; d) when individual stages are examined using 10 animals per group, only Stage VII has 80% or greater power of test (alpha = 0.05) to detect a frequency difference; e) pooling stages into 3-4 groups is recommended to improve the power of detecting a treatment difference. PMID- 2271734 TI - Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: light microscopic observations of perfusion-fixed and plastic-embedded testes. AB - The stages of the cycle in the rat seminiferous epithelium are illustrated for testes fixed by vascular perfusion and embedded in plastic resins. Improved cellular resolution in plastic sections permitted a clearer demarcation of the stages than in paraffin. Quantitative data are presented to support the recognition of stages, particularly those in transition. Stages IV, V, VII, XI, and XII had the highest frequencies of transitional characteristics. Stage IV was redefined to be more consistent with the occurrence of a high percentage of mitotic figures and to clarify transitions in this stage. Although the resolution of cellular detail was greatly improved with the use of plastics, the thinner sections contained fewer identifying features together within a single tubule cross section and sometimes major characteristics were absent. Therefore, additional characteristics were used for stage classification, such as nuclear diameter and the presence or absence of mitotic figures. A binary decision key is provided to improve consistency among laboratories in the identification of the stages in plastic-embedded testes. PMID- 2271735 TI - The therapeutic control of acid secretion in gastric ulcer: a critical appraisal. PMID- 2271736 TI - Altered skin temperature and electromyographic activity in the irritable bowel syndrome. AB - A prospective study to determine the presence or absence of any difference in skin temperature and electromyographic (EMG) activity in 20 patients with irritable bowel syndrome (IBS) compared with 20 age- and sex-matched controls was conducted. A representative digital temperature and EMG activity during 4 phases, baseline, mental activity (arithmetic), unpleasant thoughts and audio biofeedback relaxation, were recorded using standard biofeedback equipment. Results showed the IBS group to have a significantly lower digital temperature and significantly higher EMG activity during the baseline and arithmetic phases. No difference was found in EMG activity for the unpleasant thought or audio biofeedback relaxation phases. Indeed, the IBS group were able to achieve a level of EMG activity during the audio feedback relaxation phase that approximated very closely that of the control group. These results provide further evidence suggestive of altered autonomic nervous system function in IBS patients and indicate that further studies should be undertaken to determine whether the reduction achieved in EMG activity post-relaxation is sustained, and if so, if it is associated with a corresponding improvement in symptoms. PMID- 2271737 TI - Plasma oxypurines in gastric and colorectal cancer. AB - Reverse phase high performance liquid chromatography has been used for the determination of plasma hypoxanthine, xanthine, and uric acid in normal subjects and in patients with gastric and colorectal cancer. Plasma oxypurines are significantly elevated in either type of cancer, while uric acid concentration is only higher in gastric cancer. The variations are related to the stage of the tumors, and the physiopathology of their occurrence is discussed. PMID- 2271738 TI - Role of intracellular organelles in the hepatic transport of bile acids. AB - The intracellular events associated with the vectorial transport of bile acids by the hepatocytes from the sinusoidal pole to the canalicular pole are reviewed. Binding to cytosolic proteins occurs. The role of this binding is to prevent efflux from the cytosol back into the blood. There is evidence from electron microscopy, from autoradiography and from immunoperoxidase observations that bile acids interact with the endoplasmic reticulum and the Golgi apparatus. There is also evidence that a carrier system or taurocholate exists on the Golgi membrane. We propose that a vesicular pathway involving the Golgi apparatus and dependent on the integrity of microtubules may play a role in bile acid transport in the cell. Inhibition of bile acid transport by microtubule poisons is consistent with this hypothesis. Finally, monohydroxylated, cholestatic bile acids such as lithocholate and taurolithocholate interact with the endoplasmic reticulum. This interaction results in a depletion of the endoplasmic reticulum calcium stores and an increase in intracellular ionized calcium. The relationship of this novel effect of bile acids to their cholestatic properties remains to be elucidated. PMID- 2271739 TI - Chronic fluorine poisoning in man: a review of literature in English (1946-1989) and indications for research. PMID- 2271740 TI - Adverse effects of inhaled corticosteroids. AB - Corticosteroids have a significant role in the management of asthma due to their powerful anti-inflammatory actions. However, when given orally, they cause significant and unwanted side-effects. Early attempts to circumvent these side effects were largely unsuccessful. Recently, new synthetic corticosteroids have been developed that have powerful topical action but weak generalised effects due to rapid systemic metabolism. These new compounds provide adequate control of airways' obstruction in almost all asthmatics. Oral candidiasis may occur but can generally be controlled by adjusting the frequency of dosage and changing delivery systems. In high doses, there is biochemical evidence of adrenal suppression, but the clinical importance of this is not yet clear and there is no evidence of a significant effect on growth in children. High dose inhaled corticosteroids have been shown to affect biochemical indices of bone turnover in the short term. The long term clinical consequences of this are still under evaluation. Inhaled corticosteroids have provided a significant advance in the management of asthma, but physicians need to remain alert for the possibility of systemic side effects when used in high doses for long periods of time. PMID- 2271741 TI - Distribution of IL-3 activity in mice transplanted with IL-3 producing T cells (STIL-3): abrogation of the distribution of STIL-3 cells into the liver and liver hemopoiesis by splenectomy. AB - Distribution of IL-3 producing T cells, STIL-3, in splenectomized mice after intravenous injection was studied in order to determine the site of IL-3 production in the splenectomized mice. Hematological features of STIL-3 inoculated mice after splenectomy were also studied. Splenectomy prior to inoculation of STIL-3 cells resulted in a slight increase in the level of IL-3 activity in most lymphohemopoietic tissues, but resulted in a slight decrease in the level of IL-3 activity in the plasma. The splenectomy also abrogated granulocytosis which was evident in sham-operated host mice. Hepatomegaly and a number of granulocytic foci in the liver were observed in STIL-3 inoculated mice, but this was again abrogated completely by the splenectomy. These results suggest that the spleen is the major site of granulopoiesis in response to the stimulus with IL-3, and also that the spleen is essential for the migration or metastasis of STIL-3 cells to the liver. PMID- 2271742 TI - Pulmonary toxicity of oxygen. AB - Prolonged exposure to hyperoxia in order to compensate for inefficient ventilation can lead to progressive pulmonary damage and death. Since pulmonary macrophages control bacterial and viral penetration, we studied the effect of hyperoxia on pulmonary alveolar macrophages from newborn and adult rats, kept in air or in a 95% normobaric oxygen atmosphere. The viability of pulmonary alveolar macrophages in bronchoalveolar lavages of newborn rats after 3 d in oxygen was significantly lower than that of newborn rats after 3 days in air. The functional capacity, as measured by the phagocytosis of Candida was similarly affected and these observations mays explain why infections develop. Adult rat macrophages were not sensitive to hyperoxia. PMID- 2271743 TI - Regional pharmacokinetics. I. Physiological and physicochemical basis. AB - Systemic pharmacokinetics is the study of the time-course of drug concentrations in 'systemic' blood sampled from either an arterial, central venous or peripheral venous blood vessel. It is generally not suitable for studying the pharmacokinetics of drugs in individual organs of the body, when the blood concentrations of a drug are changing rapidly, or when the physiological or pathophysiological status of a patient is unstable. Regional pharmacokinetics addresses some of these limitations and is based on the study of the factors influencing drug concentrations in specific regions (tissues, organs) of the body due to the movement of drug from blood into and out of the region (drug 'uptake' and 'elution', respectively). It provides a vital link between systemic pharmacokinetics and molecular pharmacology. The physiological basis of regional pharmacokinetics is a function of the interactions of the drug between the cells and proteins in blood, the blood flow supplying a region, the structure of the capillaries of the region and the types of specific and non-specific binding within the region. The physicochemical basis of regional pharmacokinetics is a function of the factors influencing the rate and extent of diffusion of a drug through aqueous and lipid mediums, such as molecular weight, ionization, charge, and lipophilicity. PMID- 2271744 TI - Placental transfer and tissue distribution of vitamin E in pregnant rabbits. AB - alpha-Tocopherol (vitamin E) is widely prescribed in neonatal intensive care units, in large doses and by different schedules, for the prevention of retrolental fibroplasia, intraventricular haemorrhage, bronchopulmonary dysplasia, and haemolytic anaemia. Since the efficacy of the drug in premature newborns seems related to early administration, the physicochemical characteristics of the drug itself and available formulations limit the major therapeutic aim of promptly raising levels of vitamin E in premature babies during the early hours of life. It has thus been suggested that vitamin E be given to the mother before delivery to produce higher drug concentrations in the newborn. To see whether this would work, the tissue distribution and transplacental transfer of vitamin E were studied in six pregnant rabbits at steady-state after an i.v. bolus + infusion to give a mean venous blood concentration of about 325 mumol l-1 of alpha-tocopherol acetate, corresponding to about 30 mumol l-1 of alpha-tocopherol. Endogenous levels were measured in six control pregnant rabbits. In treated animals alpha-tocopherol was increased in liver, spleen, placenta, lung, mammary gland, blood, and bile but not in brain, heart, fat, muscle or adrenals probably because distribution into these tissues is very slow. Vitamin E levels in the placenta of treated mothers were 15 times those of control rabbits, but the vitamin was not detectable in amniotic fluid and only very low levels were found in fetal blood. These findings do not indicate any advantage of giving mothers alpha-tocopherol acetate before delivery. PMID- 2271745 TI - Pharmacokinetic modelling of the plasma concentration-time profile of the vitamin retinyl palmitate following intramuscular administration. AB - Seven healthy male volunteers (21-24 y) received by the ventro-gluteal route a single dose of 100,000 I.U. of the vitamin retinyl palmitate (RP) in a water miscible preparation (W) and 5 weeks later the same dose in an oily solution (S). After administration of W median (range) peak plasma concentrations of 5.6 (4.4 8.7). 10(3) micrograms l-1 were reached after 12 h and high levels persisted for another 50 h. At 144 h levels were still, by a factor 3, higher than baseline. Plasma levels of RP after S remained close to baseline (20-50 micrograms.l-1) suggesting negligibly low bioavailability. The plasma level profile of RP after W could well be described by use of a one-compartment model with Weibull-type absorption and Michaelis-Menten elimination. The median (range) absolute bio availability (estimates of lower limits) was 42 (32-52) per cent. PMID- 2271746 TI - Pharmacokinetics of midaglizole, a new hypoglycaemic agent, in healthy subjects. AB - The objective of this study was to evaluate the pharmacokinetics of midaglizole, a new orally effective hypoglycaemic agent, in healthy male subjects. In Study I, volunteers were given single oral doses of 150, 200, 300, and 500 mg of midaglizole 20 min before breakfast. In Study II, 200 mg of midaglizole was given 30 min after breakfast. In Study III, multiple oral administration study was carried out at a dose of 200 mg t.i.d. 20 min before meals for 7 days. The disposition of midaglizole was adequately described by a one-compartment open model with first order absorption. It was essentially dose-dependent up to 500 mg given orally. The pharmacokinetic parameters calculated by employing this model indicated that the disposition of this drug was characterized by good absorption from the intestine, a wide distribution in the body, and a rapid excretion via the kidneys. The absorption rate of midaglizole from the intestine was definitely slowed by the presence of food, probably due to a decrease in the rate of gastric emptying. No clinical significant accumulation of midaglizole in the body was observed during or after multiple doses. A linear correlation was found between the area under the curve of plasma concentration of midaglizole versus time and the area calculated from the curve of change in blood glucose level versus time after oral administration of midaglizole. PMID- 2271747 TI - Effect of food on the bioavailability of adinazolam from a sustained release formulation: effect of meal timing and lack of dose dumping. AB - Food effects on adinazolam absorption from sustained release (SR) adinazolam mesylate tablets were assessed in 28 healthy male volunteers. Subjects received 15 mg SR tablets, 15 mg immediate release tablets, 15 mg oral solution, administered after an overnight fast, and 15 mg SR tablets after a high fat breakfast. Treatments were administered in a crossover design. Plasma adinazolam and N-desmethyladinazolam (NDMAD) concentrations were determined by HPLC. Adinazolam and NDMAD AUC values were unaffected by food. Cmax for SR tablets was increased 33 per cent and 18 per cent for adinazolam and NDMAD, respectively, when administered postprandially. Tmax occurred later in the fed state; no dose dumping was observed. Meal timing effects on adinazolam absorption from SR tablets were assessed in 24 healthy subjects, who received 30 mg SR tablets 1 h before, 0.5 h after, 2 h after a high fat meal, and in the fasted state. Postprandial administration had no effect on AUC, but resulted later and higher adinazolam and NDMAD Cmax. Differences in these values were less than 11 per cent. Administration of SR tablets before meals yielded Cmax and Tmax values which were similar to the fasted state. Results suggest that meal timing does not substantially affect adinazolam absorption from the SR tablet. PMID- 2271748 TI - Influence of liquids (coffee and orange juice) on the bioavailability of tetracycline. PMID- 2271749 TI - Interaction of ethanol, quinidine, and sparteine with the metabolism of nifedipine by Cunninghamella echinulata. PMID- 2271750 TI - Regional pharmacokinetics. II. Experimental methods. AB - Regional pharmacokinetics is the study of the drug concentrations in specific regions of the body. It allows greater insight into the mechanisms of drug disposition than the study of systemic blood concentrations. Experimental methods in regional pharmacokinetics and their applications and limitations are reviewed. Post-mortem tissue biopsies give the drug concentrations in highly specific regions of the body, but require a large number of animals. Serial tissue biopsies yield the time-course of drug concentrations in individual animals, but have limited applications. Regional blood sampling in vivo requires catheterization of blood vessels and a measure of regional blood flow, but allows repeated measurements of the time-course of regional drug concentrations in an individual. In contrast, artificially perfused regions allow greater control of perfusate flow and composition, but are less representative of the in vivo situation. These factors can be retained in some animals by surgically transplanting organs to another location to increase access. Tissues slices and cell cultures can examine drug uptake in the absence of perfusion, and tissue homogenates can be used to study the in vitro rates of drug metabolism and tissue drug binding. PMID- 2271752 TI - Pharmacokinetics of sulfamethoxazole and trimethoprim in Mexicans: bioequivalence of two oral formulations (URO-TS D and Bactrim F). AB - Two oral pharmaceutical formulations (URO-TS D and Bactrim F) containing 800 mg of sulfamethoxazole (SMZ) and 160 mg of trimethoprim (TMP) were given to 10 Mexican healthy volunteers, following a randomized cross-over design. Blood and urine samples were obtained, concentrations of TMP, SMZ, and its metabolite N4 acetyl SMZ were measured by HPLC and pharmacokinetic analyses were performed. The observed Cmax, tmax, half-life, AUC, and cumulative urinary excretion values for the three compounds studied were within the ranges that have been previously reported for European and North American subjects. Therefore, it appears that pharmacokinetics of SMZ and TMP in Mexicans are similar to those observed in Caucasian populations. When the two studied formulations were compared, no statistically significant differences were detected in any pharmacokinetic parameter. Therefore, it is concluded that both brands tested are bioequivalent. Moreover, these two formulations manufactured in Mexico yield SMZ and TMP plasma and urine levels similar to those obtained with equivalent formulations of European or North American origin. PMID- 2271751 TI - The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride. AB - The influence of hepatic disease on the pharmacokinetics of the new ACE inhibitor, benazepril hydrochloride, was evaluated in 12 male patients suffering from liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged benazepril and its active metabolite benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same benazepril. HC1 dose, the plasma concentrations of benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of benazeprilat. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive prodrug benazepril to the active benazeprilat were virtually unaffected by hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver. PMID- 2271753 TI - Disposition of phenytoin in analbuminemic rats. AB - The disposition characteristics of phenytoin were investigated in analbuminemic rats to study the effect of plasma protein binding on phenytoin disposition. Blood and plasma phenytoin concentration determinations, measurement of plasma protein phenytoin binding, and whole-body autoradiography were performed after intravenous bolus injection of 10 mg kg-1 of phenytoin. When plasma phenytoin was assayed, total body phenytoin clearance (CL) was faster and its apparent volume of distribution (Vd) greater in the analbuminemic rats in comparison to the controls. The plasma protein binding of phenytoin was significantly lower in the analbuminemic rats, suggesting the disposition characteristics of phenytoin were altered in the presence of low plasma albumin concentrations due to reduced plasma phenytoin protein binding. On the other hand, when blood phenytoin levels were analyzed, no difference in CL and a less pronounced difference in Vd were noted between the two groups of rats. The red blood cell-to-plasma phenytoin concentration ratios were greater in analbuminemic rats, suggesting that the distribution of phenytoin into red blood cells was greater in the mutant rats. PMID- 2271754 TI - Pharmacokinetics of urinary metabolites of cannabidiol in the dog. AB - The pharmacokinetics of cannabidiol (CBD) and six of its urinary metabolites was investigated in dogs. CBD was administered intravenously to three dogs, and urine was collected at specified time intervals over a period of 30 h. The apparent terminal half-life of CBD calculated from the slope of the sigma minus plot was significantly shorter (2 h) than the half-life of CBD calculated from plasma data (8 h), and the apparent terminal half-life of the metabolites was similar to that of the CBD calculated from plasma data, indicating that the elimination of these metabolites was formation rate limited. The time course of the metabolite excretion could be divided into two phases: the first phase contained mainly monohydroxy metabolites, and the second phase contained mainly metabolites with a carboxylic acid moiety in their side-chain. PMID- 2271755 TI - Pharmacokinetics of dibenzylamine administered in a sustained drug delivery system with cefazolin. AB - The pharmacokinetics of dibenzylamine administered in a sustained drug delivery system with cefazolin was studied after i.m. administration of a dose of 1250 mg to healthy volunteers. The serum and urine levels of dibenzylamine were determined by a GLC technique using a specific nitrogen-phosphorus detector. Characterization of the kinetic parameters was performed by applying compartmental and non-compartmental analysis. Dibenzylamine was found to reach concentrations close to 300 ng ml-1 approximately 5 h after administration. The elimination constant had a value of 0.832 +/- 0.821 h-1 (mean +/- S.D.), which is higher than the release constant of the derivative (0.109 +/- 0.072 h-1) (mean +/ S.D.). These results show that release of dibenzylamine may be considered the limiting kinetic process, which governs the elimination of the product from the organism. Only a small amount of dibenzylamine is excreted in urine unchanged 3.43 +/- 3.28 per cent (mean +/- S.D.). Using the pharmacokinetic parameters calculated for dibenzylamine, a prediction has been made of the concentrations reached in a multiple dosage regimen after administration of a dose of 1250 mg every 24 h. The accumulation factor was 1.09. PMID- 2271756 TI - Casson fluid model for pulsatile flow of blood under periodic body acceleration. AB - Pulsatile flow of a Casson fluid under the influence of a periodic body acceleration has been studied in this paper. An implicit finite difference numerical procedure has been used to analyze the flow. Applicability of this method has been checked by comparing the obtained results with the analytical solution for Newtonian flow and explicit scheme solution. The agreement between the implicit and explicit scheme solutions and the analytical solution is good (error less than 1%). Flow variables have been computed at three locations in cardiovascular system (wide (femoral) and narrow (arteriole and coronary) tubes). Effects of yield stress, tube radius and pressure gradient combined, body acceleration amplitude and frequency etc., on flow have been studied. The following observations have been made: (i) Initial transient time It changes with yield stress in narrow tubes are insignificant, whereas in wide tubes It decreases with yield stress; (ii) The axial velocity and fluid acceleration variations with yield stress are uniform (changes only quantitatively, profiles shape remain same) in narrow tubes, whereas in wide tubes these variations are non-uniform (profiles change qualitatively as well as quantitatively); (iii) Yield stress effects on wall shear amplitude are insignificant in narrow tubes (congruent to 0.3% in arteriole and congruent to 6% in femoral); and (iv) For Newtonian fluid, mean flow rate does not change with body acceleration amplitude a0 and frequency fb but it increases (decreases) with a0(fb) for Casson fluid. PMID- 2271757 TI - Effects of drag reducing polymer on atherosclerosis. AB - In order to determine the effect of drag reducing polymers on the occurrence of atherosclerosis, the Guinea pigs were used as the experimental animals. The inhibitory effect of a drag reducing polymer (polyacrylamide) on atherosclerosis in the aortas of Guinea pigs on a high cholesterol diet (2%) was investigated over a period of 6 months. The aortas, livers, kidneys and lungs of the animals, which were separated into four experimental groups (control, polymer, cholesterol and cholesterol + polymer) were also investigated both macroscopically and light microscopically. The selected physiological parameters such as, plasma cholesterol levels, plasma hemoglobin, hematocrit and total lipid values were determined at regular intervals for each group. The results indicate that the atherosclerosis in aorta of the animals receiving the polymer injection is suppressed significantly and the drag reducing water soluble polymers may be effectively applied against atherosclerosis. PMID- 2271758 TI - Fatty streak development in the vicinity of aortic coarctations in hypercholesterolemic rabbits. AB - The influence of altered local hemodynamics on fatty streak development in rabbits fed high cholesterol diets was investigated. An aortic coarctation was created in the abdominal aorta of nine rabbits by placing a partially constricting gold or silver band (1.7 mm x 10 mm) around the aorta between the renal arteries and aortic bifurcation. Controls were 20 rabbits; seven sham operated and 13 unoperated rabbits. The abdominal aorta 1-2 cm proximal to the coarctation showed lipid deposition involving 45 +/- 8% (mean +/- SEM) of the luminal surface which was more than occurred within or distal to the obstruction (p less than 0.05) and also more than in controls (p less than 0.05). Within the coarctation, 4 +/- 2% of the luminal surface showed lipid deposition which was less than either proximally or distally (p less than 0.01) and also less than in comparable regions in controls (p less than 0.05). The aorta 1-2 cm distal to the coarctation showed lipid deposition involving 18 +/- 4% of the surface which was similar to control rabbits. Lipid deposition in corresponding regions of the control rabbits was involved in 17 +/- 4%, 19 +/- 5% and 19 +/- 4% of the luminal surface, respectively. Fatty streak development, therefore, appeared to be inhibited within the coarctation and enhanced proximal to it. The results suggest that some early step in the process of lipid accumulation may be affected by local fluid dynamics or modification of the wall of the vessel. PMID- 2271759 TI - Clinical assessment of rheumatic diseases using viscoelastic parameters for synovial fluid. AB - For the first time it is clearly exhibited that synovial fluid (SF) is thixotropic. Although no hysteresis loops were observed for SF, not even at high shear rates, thixotropy may be exhibited by measuring the rate of recovery after extensive shearing. The rebuilding of the structure in a small-amplitude oscillatory state following the high-shear-rate state reveals the thixotropic behaviour. Five different viscoelastic parameters for various synovial fluids (SF) were obtained using oscillatory rheometry. It was also shown that for SF in the low frequency range, corresponding to a knee joint almost at rest, the shear loss modulus G" is greater than the shear storage modulus G', since the system is allowed to dissipate energy at rest. However, with movement, G' increases and eventually becomes greater than G" at a characteristic frequency above which the system has insufficient time to dissipate energy and hence responds as an elastic body. This functional behaviour, characteristic for normal SF, broke down in the SF of rheumatoid arthritis. It was also absent in the SF of knee joints with meniscus lesions and ligament defects. PMID- 2271760 TI - Fluid shear stress enhanced DNA synthesis in cultured endothelial cells during repair of mechanical denudation. AB - We have previously observed a stimulatory effect of fluid shear stress on the regeneration of cultured endothelial cell layers after mechanical denudation. In this study we examined how fluid shear stress affects endothelial cell DNA synthesis during regeneration. Following mechanical denudation of narrow linear areas, monolayers of bovine aortic endothelial cells cultured on plastic dishes were subjected to shear stress of 1.3-4.1 dynes/cm2 for 24-48 hours in a specially designed apparatus. After the application of shear stress, cells were stained with propidium iodide, and its fluorescence intensity, reflecting cellular DNA content, was measured using photometric fluorescence microscopy. The DNA content of cells exposed to shear stress increased significantly more than that of paired, static control cells (p less than 0.005 to p less than 0.001). The DNA histogram showed that cells exposed to shear stress contained a relatively high proportion of cells located in the S, G2, and M phases of the cell cycle as compared with the static control. These data suggest that fluid shear stress enhances endothelial cell DNA synthesis during the repair of mechanical denudation. PMID- 2271761 TI - Light transmission through blood in oscillatory flow. AB - Measurements were made of the intensity of light transmitted through various thicknesses of normal human blood confined between two parallel plane surfaces, one fixed and the other oscillating in its own plane. When the light propagation direction is perpendicular to the direction of shear flow the transmitted intensity contains a steady component and a dominant second harmonic of the oscillation frequency. For a thin layer of blood, the steady intensity is a minimum value when the oscillation amplitude produces unit strain. The second harmonic is very small at small strains, but increases rapidly near unit strain where it is approximately in phase with the strain. For thicker layers, the effects of viscoelastic shear waves reduce the size of the second harmonic and modify its phase. Changes in light transmission are interpreted by relating the optical density of the blood to the total amount of contact between red cells. In oscillatory flow at low strains (less than 1) cell-to-cell contact is reduced by disaggregation of cell groups, and light transmission decreases. Near unit strain, disaggregation becomes complete, cell alignment occurs, and light transmission is minimized. At higher strains cell-to-cell contact is increased by formation of aligned layers of compacted cells separated by parallel plasma layers, and light transmission increases. PMID- 2271762 TI - The influence of calcium on the deformability of human granulocytes. AB - Experiments were carried out to determine the importance of extra- and intracellular calcium for the deformability of granulocytes during filtration tests. At low calcium concentration (0.1 mM), granulocytes are more deformable than at the physiological free-calcium concentration of 1.25 mM. Increasing calcium concentrations up to 10 mM do not further impair the deformability. Parallel measurements of the intracellular calcium concentration by means of the fura fluorescence method were performed to explain this. Extracellular calcium concentrations between 1.25 mM and 10 mM had no influence on the intracellular calcium level. A lower extracellular calcium concentration (0.1 mM), however, decreased the intracellular calcium level. Therefore, the measurements of the intracellular calcium concentrations are consistent with the deformability results. Studies with the calcium entry blocker nifedipine suggested that a low intracellular calcium improves the deformability of granulocytes. It is concluded; (i) the physiological calcium concentration of 1.25 mM is stressful for isolated granulocytes, and (ii) the intracellular calcium level plays a crucial role in granulocyte deformability, i.e. the lower the intracellular calcium concentration the greater the deformability. PMID- 2271763 TI - Flow of non-Newtonian blood analog fluids in rigid curved and straight artery models. AB - The influence of non-Newtonian rheology on wall shear rate in steady and oscillatory flow through rigid curved and straight artery models was studied experimentally. Wall shear rates measured by flush mounted hot film anemometry under nearly identical flow conditions are reported for the following four fluids: aqueous glycerin (Newtonian), aqueous polyacrylamide (shear thinning, highly elastic), aqueous Xanthan gum (shear thinning, moderately elastic), and bovine blood. For steady flow conditions there was little difference at any measurement site in the wall shear rate levels measured for the four fluids. However, large differences were apparent for oscillatory flows, particularly at the inner curvature 180 degrees from the entrance of the curved artery model. At that position the peak wall shear rate for polyacrylamide was 5-6 times higher than for glycerin and 2-3 times higher than for bovine blood. It is concluded that polyacylamide is too elastic to provide a good model of blood flow under oscillatory conditions, particularly when there is wall shear reversal. Xanthan gum and glycerin are better analog fluids, but neither is entirely satisfactory. PMID- 2271764 TI - Erythrocyte shape simulation by numerical optimization. AB - In a recent paper we examined the morphology of erythrocytes in terms of the mean mean curvature (MMC) of their cell membranes. A computer simulation of these shapes based on the different geometries showed that the MMC increased from the sphero-stomatocyte to the spheroechinocyte via the discocyte. In this work we extend this analysis by using a numerical optimization method based on importance sampling and the principle of adiabatic cooling. The erythrocyte membrane is treated as a single closed fluid lamina exhibiting viscoelastic characteristics. The energy function of the lamina includes the following terms: (i) Curvature elastic energy terms which depend on both local and global curvature. (ii) A term describing the compression elasticity of the lamina. (iii) A term which depends on the volume of the cell and which is related to the osmotic pressure across the membrane. In the simulation the cell is assumed to have axial symmetry and it can therefore be described by a finite set of conic sections. So far we have been able to obtain an energy minimum corresponding to a discocyte shape using a sphere as the initial configuration. Our results therefore imply that the well known sequence of erythrocyte shapes could solely be governed by the above mentioned properties of an ideal fluid forming a closed singly connected lamina. PMID- 2271765 TI - Pulsatile flow of power-law fluid model for blood flow under periodic body acceleration. AB - A mathematical model has been proposed to study the pulsatile flow of a power-law fluid through rigid circular tubes under the influence of a periodic body acceleration. Numerical solutions have been obtained by using finite difference method. The accuracy of the numerical procedure has been checked by comparing the obtained numerical results with other numerical and analytical solutions. It is found that the agreement between them is quite good. Interaction of non-Newtonian nature of fluid with the body acceleration has been investigated by using the physiological data for two particular cases (coronary and femoral arteries). The axial velocity, fluid acceleration, wall shear stress and instantaneous volume flow rate have been computed and their variations with different parameters have been analyzed. The following important observations have been made: (i) The velocity and acceleration profiles can have more than one maxima, this is in contrast with usual parabolic profiles where they have only one maximum at the axis. As n increases, the maxima shift towards the axis; (ii) For the flow with no body acceleration, the amplitude of both, wall shear and flow rate, increases with n, whereas for the flow with body acceleration, the amplitude of wall shear (flow rate) increases (decreases) as n increases; (iii) In the absence of body acceleration, pseudoplastic (dilatant) fluids, with low frequency pulsations, have higher (lower) value of maximum flow rate Qmax than Newtonian fluids, whereas for high frequencies, opposite behavior has been observed; for flow with body acceleration pulsations gives higher (lower) value of Qmax for pseudoplastic (dilatant) fluids than Newtonian fluids. PMID- 2271766 TI - A computer simulation of the creep process of the cell wall using stress relaxation parameters. AB - The stress relaxation of the cell wall of pea plants was measured and viscoelastic parameters were obtained according to the stress-relaxation analysis developed by Yamamoto et al. (Plant & Cell Physiol. 1970). The creep process of the cell wall was simulated by a numerical integration using stress-relaxation parameters, because the direct conversion of the stress relaxation process to the creep is impractical. In the conversion, a personal computer was programmed for the Maxwell viscoelastic model with a compiler language. Cell wall creep was measured with a specially constituted apparatus and compared with that calculated by the simulation process. The results suggested that the creep can be reproduced by a computer simulation using the stress-relaxation parameters. Both creep and stress-relaxation properties of plant cell walls can be analyzed by using a single model. PMID- 2271767 TI - Effect of electric field on erythrocyte sedimentation rate. II. Dependence on electric current. AB - We measured the electric current dependence of sedimentation curves of swine erythrocytes in a saline solution at the volume fraction of erythrocytes H = 0.091 and 0.220. The sedimentation curve fitted well to the exponential type equation l = a[1-exp(-bt)] at the upward initial electric current I0 = 0.50 mA, 1.01 mA and 1.50 mA, where l is the length of the medium layer at time t, and a and b are phenomenological parameters. The initial slope v0 of sedimentation curve was enhanced from 0.68 mm/hr at I0 = 0 mA to 2.85 mm/hr, 3.87 mm/hr and 5.50 mm/hr at I0 = 0.50 mA, 1.01 mA and 1.50 mA, respectively, for H = 0.220. We also made sedimentation measurements of erythrocytes in their own plasma at H = 0.220 and 0.316. Sedimentation curves coincided with the sigmoidal type equation l = l infinity/[1 + (t50/t)beta] at I0 = 0 mA and 0.50 mA, where l infinity is l at t----infinity, t50 is the time when the plasma level falls to l infinity/2 and beta is a constant. The maximum slope vmax of sedimentation curve increased from 13.29 mm/hr at I0 = 0 mA to 18.65 mm/hr at I0 = 0.50 mA for H = 0.220. PMID- 2271769 TI - Hydraulic flow conductivity of hyaluronic acid solutions: effects of concentration and molecular weight. PMID- 2271768 TI - Blood viscosity and optimal hematocrit in narrow tubes. AB - Blood viscosity in normal adults was measured in glass tubes with diameters of 50, 100 and 500 microns for a wide range of adjusted feed hematocrits (15-70%). Blood viscosity decreased at each of the adjusted feed hematocrits when going from a 500-micron tube to a 50-micron tube. The viscosity reduction increased with increasing hematocrit. The steepness in the hematocrit-viscosity curves decreased with decreasing tube diameter. Erythrocyte transport efficiency (hematocrit/blood viscosity) was calculated to estimate the optimal hematocrit for oxygen transport. Optimal hematocrit averaged 38% in 500-micron tubes, 44% in 100-micron tubes and 51% in 50-micron tubes. Our results suggest that the strong Fahraeus-Lindqvist effect at high hematocrits may help to maintain oxygen transport in polycythemic patients as long as the driving pressure is sufficient. PMID- 2271770 TI - Influence of posture variation on fluid flow patterns in a curved tube. PMID- 2271771 TI - Animal models for the biological effects of continuous high cytokine levels. AB - Transgenic animals or animals engrafted with retrovirus-derived expression vectors provide models for studying the in vivo effects of high and continuous serum levels of cytokines. Studies employing these models in order to analyze the biological effects for granulocytes-macrophages colony-stimulating factors (CSFs), granulocytes of interleukin (IL-)2, IL-3, IL-6 and erythropoietin are reviewed. In all of these models, overexpression of the different cytokines achieved by use of these approaches resulted in syndromes that were related to nonneoplastic hyperplasia of the respective target cell population. In some but not all models, these syndromes were lethal, mostly due to hypercellularity. These models allow conclusions about the biological effects of very high and continuous levels of these substances as well as about their regulation in different tissues. PMID- 2271773 TI - Growth of normal versus leukemic bone marrow cells in long term culture from acute lymphoblastic and myeloblastic leukemias. AB - The ability of the in vitro long-term bone marrow culture (LTBMC) system to impair the survival of leukemic cells and to enhance the growth of normal progenitors has been studied. Bone marrow cells from 19 acute lymphoblastic leukemia (ALL) and 30 acute myeloid leukemia (AML) patients at diagnosis were grown in LTBMC for 4-10 weeks. In half of the cases the leukemic population declined down to undetectable levels and was replaced by putative normal hemopoietic precursors, both in ALL and in AML. In the remaining cases, leukemic cells persisted throughout the culture time and few if any normal hemopoietic cells were detected. These data led us to extend to the lymphoid compartment the previous observation of decreasing leukemic myeloid blasts in LTBMC. The potential of such cultures as an in vitro purging system for autologous bone marrow transplantation in selected poor-prognosis lymphoid malignancies should be explored, as has been done for acute and chronic myeloid leukemias. PMID- 2271774 TI - Phenotypic analysis of a large number of normal human bone marrow sample by flow cytometry. AB - Bone marrow aspirates from 48 healthy donors (34 adults, 14 children) were analyzed by flow cytometry (FACS Analyzer) after purification of low-density bone marrow cells (Ld BMC) on a density gradient (d = 1,077) and labelling with 23 anti-hematopoietic cell monoclonal antibodies. Based on physical properties, these Ld BMC could be divided into four different populations called E, My, Mo and L, which comprised 14% +/- 9%, 31% +/- 16%, 10% +/- 5% and 45% +/- 14% of these cells, respectively. The phenotypic analysis of these different populations enabled the identification in E, of erythrocytes (Glycophorin A+, Rhesus D+, but negative for early erythroid differentiation markers such as the transferrin receptor (Tf. R) and the FA6-152 antigen); in My of cells of the myeloid lineage (VIM2+, HLA DR-); in Mo of cells of the monocytic lineage (VIM2+, CD14+) plus some myeloblasts (VIM2+, CD14-, HLADR+) and finally in L of a heterogeneous population including: 1. T lymphocytes labelled to the same extent by CD2, CD3, CD5 and CD6 (28% +/- 10%), B lymphocytes assessed by CD19 and CD20 (12% +/- 8%), Pre-B cells (CD10+ = 8% +/- 7%), less than 5% of "natural killer" cells (CD16+ or Leu7+) and finally, less than 6% of myelomonocytes (CD14+ and/or VIM2+). 2. The erythroid lineage (rhesus D+ = 42% +/- 20%, Tf.R+ and FA6-152+ = 32% +/- 12%). 3. Undifferentiated cells or progenitor cells (CD34+ = 7% +/- 5%). 4. Cells unlabelled by any antibodies (approximately 6%). We observed no difference between bone marrow samples from adults or children, with respect to physical properties, and with all but four immunological markers. A significantly higher proportion of B cells (CD19+ and CD10+) (P less than 0.001) and undifferentiated cells (CD34+ and HLADR+) (P less than 0.02) was observed in children. These data, obtained from a large number of bone marrow samples, could be used to quantify the imbalance of some bone marrow disorders. PMID- 2271772 TI - FXII. AB - The plasma protein FXII (Hageman factor) has been shown to be linked with the plasma defence systems of coagulation, fibrinolysis, kallikrein-kinin and complement. It can be activated by surface contact activation and in solution. Surface contact activation is a complex phenomenon involving negatively charged surfaces, FXII, high molecular weight kininogen and plasma kallikrein. Fluid phase activation can be effected by a variety of serine proteases. In both types of activation the FXII zymogen is converted to active enzymes. FXII levels in plasma are low or undetectable in both inherited deficiencies and in a variety of clinical conditions. FXII levels can also be elevated in some clinical conditions. Although discovered as a clotting protein FXII appears to play an important role in the kallikrein-kinin and fibrinolytic systems and also has effects on cells. Recent studies suggest that therapeutic blockade of activation of FXII can be of benefit in certain clinical conditions. PMID- 2271775 TI - Neutralization of inhibitory activity derived from cells of MDS patients and ML-2 cell line by monoclonal antibodies against H and L-subunit-rich ferritins. AB - Monoclonal antibody 2A4 against human heart ferritin and a polyclonal antibody against human placental ferritin inactivated the suppressor activity present in media conditioned by cells of patients with myelodysplastic syndrome (MDS). These antibodies also neutralized the inhibitory activity released by cells of myeloid leukemic ML-2 cell line. In contrast, a monoclonal antibody against the ferritin L subunit did not neutralize the inhibitory activity of the media conditioned either by the cells of patients with MDS or by the ML-2 cell line. Neutralization of the inhibitory activity present in supernatants of cells of MDS patients and the ML-2 cell line by monoclonal antibodies against the H subunit of ferritin strongly indicates that the inhibitory activity resides in the acidic isoferritin molecule. PMID- 2271777 TI - Kinetics of megakaryocyte progenitor cells in idiopathic thrombocytopenic purpura. AB - The number and proliferative state of megakaryocyte progenitor cells (CFU-Meg) were compared between 13 patients with idiopathic thrombocytopenic purpura (ITP) and hematologically normal controls. The mean frequency of CFU-Meg assayed by the plasma clot method was 27.8 +/- 12.2 (+/- SD)/2 x 10(5) bone marrow light-density cells for the ITP patients, which did not differ significantly from the control value of 31.9 +/- 16.1. The percentage of CFU-Meg in DNA synthesis estimated by the 3H-thymidine suicide technique was 41.3% +/- 9.2% in ITP, which was significantly greater than the control value of 27.1% +/- 7.4% (P less than 0.01). The megakaryocyte counts for histological sections prepared from bone marrow aspirates from the ITP patients and controls were 34.5 +/- 8.5/mm2 and 11.2 +/- 5.8/mm2, respectively, with the difference being highly significant (P less than 0.001). These results suggest that increased cycling activity in a quantitatively unchanged CFU-Meg pool may lead to increased megakaryocytes in the bone marrow of ITP patients. PMID- 2271776 TI - Hemostatic and fibrinolytic parameters in patients with acute myeloid leukemia: activation of blood coagulation, fibrinolysis and unspecific proteolysis. AB - Blood coagulation, fibrinolytic and unspecific proteolytic parameters were investigated in 34 patients with acute myeloid leukemia. An increased activity of the coagulation system, documented by elevated thrombin-antithrombin III-complex (TAT) plasma levels, was found in 91% of the patients; 50% had increased elastase plasma levels. Hyperfibrinolysis, as shown by elevated fibrin split-product D Dimer plasma levels, was detected in 91% of AML patients. Activation of these enzyme systems was not associated with relevant defects in blood coagulation or fibrinolysis in the majority of the patients investigated. In selected cases of promyelocytic M3 and monoblastic M5 leukemia, however, hypofibrinogenemia and alpha 2-plasmininhibitor deficiency was found, most likely due to depletion of these proteins in the course of disseminated intravascular coagulation and secondary hyperfibrinolysis. Significant correlations were calculated between TAT and fibrinogen (r = -0.57, P less than 0.005), TAT and D-Dimer (r = 0.89, P less than 0.0005), and D-Dimer and alpha 2-plasmininhibitor (r = -0.77, P less than 0.0005) levels. Indications of a pathogenetic importance of primary hyperfibrinolysis or unspecific proteolysis for hypofibrinogenemia and alpha 2-PI deficiency were not found. PMID- 2271778 TI - Evidence for increased intracellular transport of m-sarcolysine (alkylating moiety) when combined with two amino acid analogs (PTT-119). AB - PTT-119 is an antineoplastic agent in which an alkylating moiety, m-sarcolysine, is linked to two amino acid analogs. Previous studies showed a higher "in vitro" cytotoxicity of PTT-119 when compared to free m-sarcolysine; the mechanisms of this enhanced activity are not completely understood. In this study we incubated peripheral blood cells from 8 chronic lymphocytic leukemia patients with both m sarcolysine and equimolar concentrations of PTT-119, measuring the intracellular concentration of the alkylating moiety. We observed a significantly higher intracellular concentration of m-sarcolysine in cells incubated with the peptide bound drug than with the free drug (58.3 +/- 39.6 versus 4.4 +/- 1.9 ng/10(6) cells; P = 0.013). This observation could explain the higher cytotoxic activity of PTT-119 and the lack of cross-resistance with melphalan. PMID- 2271779 TI - Post-transfusion malaria in thalassaemia patients. AB - A total of 125 beta-thalassaemia patients receiving repeated blood transfusions were screened by Giemsa stain, Acridine-orange stain and antigen detection for evidence of malaria infection on each visit. A total of 8 (6.4%) of the patients developed post-transfusion malaria (PMT) as confirmed by tracing the infected blood donors. A high incidence of PTM in thalassaemia patients appears to be due to the use of fresh blood and the high frequency of blood transfusions required by these patients. Antigen detection using monoclonal antibody was found to be more sensitive for diagnosis of PTM and for screening suspected donors than the conventional blood smear examination methods and is therefore recommended for routine blood donor screening to rule out malaria infection. PMID- 2271780 TI - Clonal growth and self-renewal of human myeloid leukemia cell lines (BRM and DD) in serum-free semi-solid culture. AB - Primary and secondary colony formation of two new human myeloid leukemia cell lines (BRM and DD) were studied in serum-free semisolid cultures. The results indicate that bovine serum albumin and transferrin were essential for clonal growth in chemically defined medium. Insulin contributed only moderately beneficial effects. Initial cell density was also a major modulator of plating efficiency. Positive cooperation between the leukemia cells was shown by using autologous conditioned media. This is the first serum-free culture method that allows self-renewal of human myeloid leukemia cell lines in terms of secondary colony formation in methylcellulose cultures. PMID- 2271781 TI - Sensorineural hearing loss associated with vincristine treatment. AB - We describe a 64-year-old patient with multiple myeloma who developed a sudden sensorineural hearing loss shortly after receiving chemotherapy with vincristine. Ototoxicity is not a known side effect of this drug. It would be of interest to perform repeated audiograms on patients receiving vincristine, in order to appreciate the actual ototoxicity of this drug. PMID- 2271782 TI - Monosomy 7 provides a proliferative advantage for leukemic cells under incubation with GM-CSF in vitro. PMID- 2271783 TI - Mechanisms of vitamin K antagonism. PMID- 2271784 TI - Mechanism of the antithrombotic effects of fish oil. PMID- 2271785 TI - Cardiovascular effects of omega-3 polyunsaturated fatty acids (fish oils). PMID- 2271786 TI - Anticoagulant therapy in venous thromboembolism. PMID- 2271787 TI - Thrombolytic therapy for venous thromboembolism. PMID- 2271788 TI - Antithrombotic therapy for coronary artery disease and valvular heart disease. PMID- 2271789 TI - Fibrinolytic therapy in coronary artery disease. PMID- 2271791 TI - Haematological investigation in neonates. PMID- 2271790 TI - Antithrombotic treatment of cerebrovascular disease. AB - The most common type of cerebrovascular disease is ischaemia or infarction from atherothrombosis or cardiac embolism. Antithrombotic treatment with an antiplatelet agent or anticoagulant assumes a prior clinical classification into categories of transient ischaemic attack (TIA) or minor stroke, acute partial stable stroke, stroke-in-progression, and completed stroke. Aspirin reduces the risk of stroke, myocardial infarction, and death after TIA or minor stroke secondary to atherothrombosis. Aspirin is effective in both sexes at a dose of 300 or 1200 mg/day. Ticlopidine (500 mg/day), a new antiplatelet agent, is more effective than aspirin in preventing stroke and death in patients with TIA or minor stroke. Ticlopidine (500 mg/day) is effective in preventing recurrent stroke, myocardial infarction, or vascular death in patients with completed stroke. Aspirin has not been directly shown to be effective after completed stroke. No clear evidence exists for the use of anticoagulants in atherothrombotic cerebral vascular disease in patients presenting with TIA or minor stroke, acute partial stable stroke, stroke-in-progression, or completed stroke. Anticoagulation for rheumatic valvular heart disease is effective in preventing recurrent embolism. Long-term anticoagulation of patients with mechanical prosthetic valves protects against initial embolism and prevents recurrent embolism. The addition of aspirin (500-1000 mg/day) to warfarin reduces the rate of cerebral embolism from mechanical prosthetic heart valves but is associated with increased bleeding. The addition of dipyridamole (400 mg/day) to warfarin may be more effective than aspirin in reducing the rate of cerebral embolism from mechanical prosthetic heart valves and has fewer bleeding side effects. Anticoagulation during the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke. Long-term anticoagulation of patients after the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke, recurrent myocardial infarction and death. Prophylactic anticoagulant treatment of patients with non-valvular atrial fibrillation reduces the incidence of embolism, but the optimal duration of treatment is not known. Immediate anticoagulation of patients with completed cardioembolic stroke is safe and effective in preventing recurrent embolism. PMID- 2271792 TI - Automated red cell analysis. PMID- 2271793 TI - Automated differential white cell counts: a critical appraisal. AB - The differential leukocyte count represents a substantial proportion of the workload in routine haematology laboratories. The traditional procedure, in which a technologist scans a Romanowsky-stained blood film and classifies 100 cells, is both labour-intensive and imprecise. The imprecision of the visual DLC is primarily a function of the small number of cells counted. To achieve a significant improvement, however, it would be necessary to count an enormous number of cells, which would be extremely costly in terms of human time and effort. Automation is thus desirable for both economic and clinical reasons. Of the various technological approaches proposed, only two have been developed to the level of marketable devices: digital image processing, and flow cytochemistry. In digital image processing systems, Romanowsky-stained blood films were scanned by a computer-controlled microscope, and leukocytes identified on the basis of parameters analogous to those used by human observers. These systems were relatively slow, offering only a limited degree of automation, and therefore failed to provide significant improvements in terms of workflow and counting statistics. No such instruments are currently marketed. Flow cytochemical analysers, which classify leukocytes primarily on the basis of size and myeloperoxidase activity, have been available commercially for 15 years, and their clinical utility is well established. A number of haematology analysers offer screening DLCs, providing neutrophil and lymphocyte counts in cases that do not have major abnormalities of the leukocyte population. The performance of these systems depends in large part on their operating environment. Three new automated DLC analysers employing flow cytometric technology have recently been announced, but these have not yet been formally evaluated. PMID- 2271794 TI - Neutrophil function tests. AB - The complexity of the neutrophil response to inflammation creates many difficulties for the study of neutrophil function in vitro. The environment in which a neutrophil is placed can have marked effects upon a variety of cellular functions. Quantitative tests of neutrophil function present problems not only with assay design but also in the isolation of cells from peripheral blood without disturbing their normal physiology. It is desirable to isolate neutrophils from other leukocytes because soluble factors released by other cells can influence neutrophil function, and other cells may interfere with functional assays; for example, monocytes will phagocytose opsonized particles and eosinophils contain a potent peroxidase. Attention to physical parameters such as temperature, pH or osmolarity, and rigorous exclusion of endotoxin, permits neutrophils to be isolated in a resting state. Subsequent function tests must be selected with an understanding of normal neutrophil physiology and applied with an awareness of any associated technical problems. The investigation of abnormal neutrophil responses may necessitate the screening of several tests of function; for example, defective neutrophil killing may be the result of abnormal chemotaxis, phagocytosis or degranulation. Which tests are appropriate will depend upon the questions to be answered and on the quantity of cells available for study. PMID- 2271795 TI - Immunophenotyping in haematological diagnosis. PMID- 2271796 TI - Cytogenetics in the investigation of haematological disorders. AB - Chronic and acute, myeloid and lymphatic haematological neoplasms are characterized by acquired genetic rearrangements that, in the majority of cases, can be detected as clonal chromosomal abnormalities. The aberrations are either primary, meaning that they contribute to the establishment of the neoplasm, or secondary, in which case they are acquired during the clonal evolution and malignization of the neoplastic cells. The abnormalities are non-randomly distributed; the aberration pattern differs from disease to disease and sometimes is so characteristic that individual rearrangements may be virtually pathognomonic for particular neoplasms. The cytogenetic characterization of haematological malignancies is of two-fold importance. First, the recurrent aberrations provide us with an insight into the pathogenetic mechanisms that are operative. They pinpoint those areas of the human genome that carry genes or regulatory sequences whose function is disturbed in leukaemias and lymphomas. Using DNA recombinant techniques in addition to chromosome-level investigations of these cancer-associated rearrangements, the molecular pathology of leukaemias and lymphomas is now gradually being unravelled. Second, even before the long term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have a direct clinical importance. The finding of an acquired, clonal chromosome abnormality in haematopoietic cells (-Y in old men is an exception) means that the patient has a neoplastic disease. Often, but by no means always, the type of aberration is also informative as to which type of neoplasm is present. During therapy, remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern influences prognosis and may thus be taken into account when the choice of therapy is made. PMID- 2271797 TI - Molecular biology and leukaemia diagnosis. AB - The diagnosis and classification of leukaemia started with simple morphological examination and now embraces use of special stains, cytochemistry and immunophenotyping. Genetic studies have progressed from karyotyping to detection of genetic changes within genes. The methods described in this chapter are still at an early stage of development and, so far, have provided relatively little in the way of an extension of available diagnostic information. Sometimes the methods provide extensions to existing techniques, for example by the detection of bcr rearrangements in patients who have CML or ALL but do not have a detectable Philadelphia chromosome. Another example is retrospective diagnosis of gene rearrangements using DNA from slide preparations. However, it should be noted that it has only very recently been shown that there is likely to be a causal relationship between the Ph chromosome and leukaemia. Daley et al (1990) induced CML in mice by bone marrow transplantation of cells infected with a retrovirus encoding P210bcr/abl and Heisterkamp et al (1990) produced mice transgenic for a BCR/ABL P190 DNA construct and showed that the progeny died of acute leukaemia (mostly ALL). We have not summarized studies of the incidence of activated oncogenes such as RAS in leukaemia and myelodysplasia. Such oncogenes appear to be involved in many tumours and may well indicate either a predisposition to cancer or a particular stage of malignancy, but their analysis does not at present help in making a diagnosis. It is likely that, as we understand more about the nature of the malignant process, we shall be able to use genetic techniques to enhance considerably both diagnostic and prognostic precision. PMID- 2271798 TI - Flow cytometry: clinical applications in haematology. AB - The time interval between the development of a new technique or methodology and its acceptance, if successful, as a recognized clinical application can be many years. The application of flow cytometry to reticulocyte counting, for example, has taken 8 years from the appearance of the first publication, and in 1990 it is still in its infancy as a clinical method. It is therefore a challenging task to anticipate which of the methodologies currently under development will achieve acceptance. It would be impossible to deal with all the candidates in the space available, and so a review is provided to those methods that may have potential applications in clinical haematology, together with some of the more practical details of methods that have recently been demonstrated to be viable in the clinical laboratory. The first category consists of leukocyte enumeration and studies on bone marrow, neutrophils, platelets and cellular DNA content, whilst the second covers reticulocyte counting and total red cell volume measurement. The contribution of flow cytometry to the field of immunophenotyping haematological disorders is probably unique in already being clinically acceptable. Finally, the question of quality control is addressed, as this is an essential prerequisite to the adoption of any new method in the clinical laboratory. PMID- 2271799 TI - Developing techniques in blood transfusion. AB - Expansion of transfusion medicine has led to an increasing awareness of the importance of its practice. Specialists in this branch of haematology whose main aim is to provide adequate and safe supplies of blood (and blood products) and to ensure these are used appropriately, are increasingly aware that to do this efficiently requires the development and utilization of new laboratory and technical procedures. Review of cross-matching techniques has led to the introduction of more rapid methods using low ionic strength saline. Use of monoclonal antibodies for blood grouping has made use of new technology, whilst allowing scarce human plasma to be used more appropriately for therapeutic purposes. Similarly, the implementation of a more rational approach to blood ordering, as in a maximum surgical blood-order schedule, allows for the more efficient use of donor blood. The use of microtitre plates for grouping and cross matching techniques allows for speed and economy in the transfusion laboratory. Their use is also associated with increased automation and computer use. The possibility of using solid-phase techniques, monocyte-macrophage assays and antibody-dependent cellular cytotoxicity assays introduces new techniques differing markedly from time-honoured liquid-phase serology methods. The application of flow cytometry, which has already been shown to be useful in many aspects of haematology, is also of benefit in the field of blood transfusion science. Safety of blood transfusion is an important aspect of its practice and has led to the introduction and development of screening tests for donor blood to exclude infection risks from such organisms as HIV-1, hepatitis B and non-A, non B hepatitis. Another approach to ensure the safety of transfused blood has been increased usage of autologous transfusion by means of both predeposit donation and intraoperative cell salvage. PMID- 2271800 TI - Type A behavior, personality, and sympathetic response. AB - This study examined, under two types of stress and during a typical workday, the moderating effects of the personality trait dependence/independence on the hemodynamic and catecholaminergic response in Type A individuals. During the mental stressor, Type As with strong dependency needs showed elevated heart rates and higher levels of epinephrine. During the physical stressor, they showed elevated heart rates and higher levels of norepinephrine. During the typical workday, both urinary catecholamines and mean daily heart rates were higher. It is suggested that these findings, which indicate greater sympathetic-adrenal response, are the result of a basic personality/behavior inconsistency and that Type A behavior may have an accentuated relationship to coronary disease when overlaid on a personality for which it is inconsistent. PMID- 2271801 TI - Social insecurity, anxiety, and stressful events as antecedents of depressive symptoms. AB - This study examined the combined effects on 132 normal adults of social insecurity, anxiety symptoms, and daily hassles on changes in the level of depressive symptoms over a 1-month period. It was hypothesized that social insecurity, a factor linked to coronary heart disease and sympathetic arousal, is also an important antecedent of depression for those who have experienced a high level of anxiety and chronic stress. Results of multiple regression analysis indicate that these three factors in combination (a 3-way interaction) predict changes in depressive symptoms. The nature of this interaction was more complex than hypothesized. PMID- 2271803 TI - Effects of life-event stress on anxiety and peripheral narrowing. AB - This study examined one of the mechanisms proposed to be behind the relationship between life stress and injury. Past researchers have identified a correlation between high life stress and athletic injury for contact and noncontact sports and for male and female athletes, but they did not investigate why athletes who experienced stress from life events were more prone to injury than those whose lives were low in stressful events. The authors tested the hypothesis that recreational athletes with high life-event stress would, when placed in a stressful, dual-task laboratory situation, experience greater narrowing of peripheral vision and state anxiety than recreational athletes with low life event stress. ANOVA and regression results offered support for peripheral vision deficits as a potential mechanism in the life stress-injury relationship and very minimal support the effect of elevated state anxiety. The great variability in peripheral vision changes for the groups with high life stress suggests that, for certain subjects, some unmeasured variable may be buffering the adverse impact of high life-event stress. The authors recommend that future researchers examine potential moderating variables, such as coping resources, and assess the relative contributions of psychosocial variables, stress history variables, and mediating mechanisms in predicting actual injuries. PMID- 2271802 TI - A study of the effectiveness of two group behavioral medicine interventions for patients with psychosomatic complaints. AB - This randomized, prospective study investigated the effectiveness of two group behavioral medicine interventions for primary care patients experiencing physical symptoms with a psychosocial component (eg, palpitations, gastrointestinal disturbances, headaches, malaise, sleep disorders). The subjects were 80 volunteers at a health maintenance organization (HMO) in the greater Boston area. Both interventions focused on the mind/body relationship and used didactic material, relaxation-response training, awareness training, and cognitive restructuring. The two behavioral medicine intervention groups were compared with a group that focused exclusively on information about stress management and its relation to illness. Measures of visits to the HMO and of distress from physical and psychological symptoms were obtained before the interventions and again 6 months afterward. At the 6-month follow-up, patients in the behavioral medicine groups showed significantly greater reductions in visits to the HMO and in discomfort from physical and psychological symptoms than did the patients in the information group. The results suggest that when the relationship among thoughts and behaviors and symptoms of patients with psychosomatic dysfunction is actively addressed, the patients' discomfort level and the cost of medical care can be reduced. PMID- 2271804 TI - The physiological and psychological effects of the expression and inhibition of emotion. AB - Previous work has indicated that humor enhances immunity, but the immunological effects of overt crying have not been studied. Thirty-nine women viewed sad and humorous videotapes and either inhibited or expressed overt expressions of laughter and weeping; these were observed and timed. Moods and immunity (S-IgA) were repeatedly measured. The humorous stimulus resulted in improved immunity, regardless of the overt laughter expressed; overt crying was immunosuppressive, whereas the inhibition of weeping in the context of the same sad stimulus was not. Moods were more negative following the sad stimulus and in the expression condition. The results with respect to humor are consistent with previous research; the immunosuppressive effect of overt crying is discussed in the context of various types of crying that may have different effects. PMID- 2271805 TI - [Light microscopy and electron microscopy study of the lymphatic capillaries of human dental pulp]. AB - The existence and the morphological characteristics of the lymphatic capillaries of the dental pulp have been and are yet discussed. In this study the morphological properties of the lymphatic capillaries of the healthy human dental pulp have been described at light and electron microscopy. For the investigation human enclosed incisive and canine teeth surgically extracted and permanent premolars extracted for orthodontic reasons were used. On semithin sections the lymph capillaries are detectable as vessels of 15-50 microns in diameter with a very irregular shape and a subtle wall. No pericytes or muscular cells surround the endothelial lining. At ultrastructural level the lymph capillaries show a very thin and indented wall with protrusions towards the vessels lumen or the interstitium. The connections between adjacent endothelial cells are different and variously shaped: end to end contacts, overlapping between cellular protrusions and complex interdigitations among multiple protrusions of the endothelial cells. Sometimes the overlappings between endothelial cells determine intraparietal channels in communications with the interstitium and the vessel lumen. A discontinuous basal lamina and a network of filaments and fibrils surround the endothelial wall. Between the cytoplasmic organelles micropinocytotic vesicles, multivesicular bodies and the Weibel-Palade bodies are present. PMID- 2271806 TI - [Monocrystalline aluminum dental implants in animals: a study of the peri-implant tissue]. AB - After the extraction of two molars in a dog's jaw, a single crystal alumina screw was implanted. Monthly radiographs were taken and analyzed by means of a video display computer (VDC) to obtain densitometric informations about the interface. After one year implantation, the bone segment containing the prosthesis was fixed in 4% paraformaldehyde, embedded in methacrylate and sectioned by a microtome saw. The results in light microscopy with ordinary and polarized light, in SEM and X-ray microanalysis, show the presence of a thick connective tissue layer interposed between the screw and the bone. The histological findings confirm the results obtained through the VDC analysis of the radiographic images. PMID- 2271807 TI - [A cephalometric study of the cervical and palatal movements during growth]. AB - The sagittal and anterior position of the hyoid bone is at the origin of the changes in orientation of the palatine laminae. A posterior-anterior movement of this bone allows the tongue to liberate the posterior part of the oral cavity; the palatine laminae rotate forwards and downwards. The opposite case is verified in the same way; the naso-palatine canal is a very malleable area, allowing a lowering of the anterior part of the palatine laminae. The vertical variations of the hyoid bone have little effect on the palate. PMID- 2271808 TI - [Value of gray scale analysis for the assessment of ultrasound detected structures in the area of the abdomen]. AB - The characteristics of the echo structure constitute an important criterion for the appraisal of sonograms. Since every pixel usually represents one out of 64 gray values, it should be possible to use the density as an objective parameter of the echo structure. In this study, the echogenicity of the pancreas was examined. The density of the pancreas became higher with increasing accumulation of fatty connective tissue or as a result of air in the intestine. In 42 people with varying degrees of obesity, the echo structure was compared with the gray scale distribution of the lumen of the gallbladder, aorta and the water-filled stomach. The results indicated that the increasing echodensity is attributable to reflections and scatter of the ultrasound in adjacent regions. The presence of air gave rise to the same effect. On the basis of standardized investigations at 15-minute intervals, the density and the visual index under the influence of a quick-acting simethicone preparation (Lefax) were compared. The density also decreased significantly within 30 to 45 minutes parallel to the reduction of superimpositional interferences due to air. The present investigations confirm the relevance of gray scale analysis for objective confirmation of sonographic structures. However, they make it evident that the echo pattern is quantifiable only under standardized conditions and when the projection plane is largely occupied. Misleading mixed values are measured in marginal zones and in superimpositions. PMID- 2271809 TI - Is ultrasound superior to carcinoembryonic antigen (CEA) measurement in recurrent tumor screening of patients with colorectal carcinoma? AB - Assuming that in the postoperative recurrent tumor screening CEA levels are as important as imaging techniques in elucidating the spread or the recurrence of a tumor, we examined 61 patients with colonic carcinoma. Those patients were operated curatively and were regularly controlled by clinical examination, laboratory, sonographic, endoscopic or radiological methods. In 3 patients there was a local recurrent, in 3 other patients there was a local recurrent and metastases. 8 patients showed sonographic livermetastases only, proved by computed tomography. In 6 patients CEA-levels rose. In 2 patients with sonographically confirmed metastases of the liver, there were neither clinical nor laboratory hints for metastases and the CEA-levels were normal. No one had elevated CEA-levels before detecting metastases. Our results indicate that ultrasound of the liver can detect metastases of colonic tumors earlier than clinical or laboratory sings do. Because of its greater diagnostic security, ultrasound is superior to CEA-measurement in recurrent tumor screening. PMID- 2271810 TI - Sonographic staging of gastrointestinal lymphoma. AB - The ultrasound findings of 580 patients with malignant lymphoma were reviewed. Conventional sonography was able to show different extents of distinctly hypoechoic bowel wall thickening due to lymphatic infiltration in 53 patients (9%) who had gastric (n = 37), enteric (n = 5), colonic (n = 7) or multiple (n = 4) involvement. In all patients, the diagnoses were confirmed by histological examination. Non-Hodgkin lymphomas (NHL) were found in 49 patients, while 4 had Hodgkin's disease. As part of staging procedures, sonography enabled the identification of regional and non-regional abdominal lymph node enlargement in 32 out of 53 patients, and therefore subdivides different stages of gastrointestinal lymphoma. Low grade malignant NHL of the gastrointestinal tract (n = 21) tends to represent generalized disease with secondary intestinal involvement (18 out of 21), those of high grade malignancy (n = 28) were present with both primary (n = 15) and secondary (n = 13) lymphoma of the gastrointestinal tract. The results of this study demonstrate the value of conventional ultrasound for identification of both gastrointestinal involvement as well as abdominal lymph node enlargement in lymphoma staging. PMID- 2271811 TI - [Conventional section study of thoracic organs. Improved diagnosis with compensation filters of anatomically molded acrylic glass containing lead]. AB - The diagnostic value of conventional chest tomography was improved dramatically by filters, manufactured of transparent acrylic glass containing 120 or 240 mu lead aquivalent (DuPont, Neu Isenburg). A perfect compensation of the chest anatomy and pathology in ap-pulmonary tomography can be done easily because the anatomically shaped filters are mobile-mounted in front of the x-ray tube. The position of each filter is visible on the patient's skin. This enables the radiographer to routinely obtain tomograms with diagnostic density values ranging from S = 0.4-2.0. For 6 characteristic areas this was measured in 98%. Such films allow subtle analyses of the tracheal and bronchial wall, the segmental bronchi and pulmonary vessels or pathologic lesion. Compared to cross-sectional imaging CT and MRT, the frontal tomogram shows several aspects of the hilar compartment more clearly because the main central pulmonary structures are located primarily craniocaudally. The conventional tomogram therefore supplies additional views with high spatial resolution. The clinical importance of diagnostic information obtained with ap-tomography using the ATCF are shown in 4 cases. In our hospital, the thoracic surgeon therefore demands conventional tomography with the ATCF to complete staging of benign or malignant chest disease preoperatively. PMID- 2271812 TI - [Focal steatosis]. AB - Focal fatty liver in 2 females is described. In the first patient with an increasing stenosis of the d. hepaticus com., a transitory focal fatty liver was found. In the second patient a durable focal liver steatosis in a form of a lipom (-30 HU) was covered. PMID- 2271813 TI - [Angiomyolipoma of the kidney--value of imaging procedures]. AB - The angiomyolipoma of the kidney is composed by blood vessels, smooth muscle tissue, and fat. It is important to differentiate this benign tumor from a malignant one. Two cases demonstrate the diagnostic value of the different imaging procedures. In 'typical' cases computed tomography shows the density of fat; histological examination is not necessary and follow up control with ultrasonography is sufficient. In other cases with a low part of fat histological examination cannot be missed. Angiography is not helpful for the differentiation from a malignant tumor. PMID- 2271814 TI - [Post-traumatic hematoma simulating a left-sided adrenal gland tumor]. AB - Typical signs of posttraumatic adrenal gland haematoma in computer-tomography are, besides an enlargement of the adrenal gland, a stripy infiltration of surrounding tissue and a thickening of the homolateral crus of the diaphragma, located primarily in the right adrenal gland. We report a case of an isolated enlargement of the left adrenal gland with normal surrounding tissue, which histologically proved to be a posttraumatic hematoma within the adrenal gland medulla. PMID- 2271815 TI - [Chordoma as osteolytic space-occupying lesion of the anterior lumbar spine]. AB - A case of a 78-year old woman with a chordoma destroying the second lumbal vertebra is reported. Radiologic and histologic feature of this rarely diagnosed tumor is demonstrated. An overview about the therapeutic modalities is given. PMID- 2271816 TI - [Chloroma in the blastic crisis of chronic myeloid leukemia--MR tomography findings]. AB - Granulocytic sarcomas are rare manifestations of diseases of the white corpuscles. The incidence of this type of disease is not yet known because it is so rare. We observed two patients, who had had a chronic myeloid leukemia for several years, and in whom such a tumor occurred during the development of a blastomatous crisis. Both patients were examined by MRI. With this method it is possible to depict changes of the bone marrow as well as extramedullary lesions. MRI is a highly sensitive, but a less specific method. PMID- 2271817 TI - [Conventional and Doppler echocardiography in the differential diagnosis of right heart failure]. AB - In the differential diagnosis of isolated right heart failure 1- and 2 dimensional echocardiography and Doppler echocardiography have proved to be of an increasing significance. In right ventricular dysplasia associated ventricular arrhythmias and regional abnormalities in wall motion of the right ventricle are characteristic. The evaluation of pulmonary heart disease has been extended by the estimation of pulmonary artery pressure using doppler echocardiography. In isolated right heart infarction, echocardiography can detect regional wall motion abnormalities and potential complications like intracavitary mural thrombi. In addition to pericardial calcification on chest x-ray and "dip and plateau" sign on pressure wave form, the abnormal diastolic hemodynamics can be demonstrated studying motion of interventricular septum and posterior left ventricular wall by echocardiography. Separating patients with restrictive cardiomyopathy may be difficult, if demonstration of the characteristic findings--increase of ventricular wall thickness, small ventricular cavities--is impossible. The evaluation of isolated tricuspid valve diseases has become possible non invasively by Doppler echocardiography. In the diagnosis of the rare right atrial myxomas 2-D-echocardiography is the method of choice. PMID- 2271818 TI - A time to heal. PMID- 2271819 TI - Vitamin A and measles in Third World children. PMID- 2271820 TI - HIV infection in women. PMID- 2271821 TI - Meniere's disease. PMID- 2271822 TI - Bleeding tonsils. PMID- 2271823 TI - The yellow card: mark II. PMID- 2271824 TI - Ear wax removal: a survey of current practice. AB - OBJECTIVE: To determine the methods of removing ear wax used by local general practitioners and the incidence of associated complications. DESIGN: Postal survey of 312 general practitioners serving a population of about 650,000; supplementary study of ear, nose, and throat outpatients to quantify the improvement in aural acuity after wax removal. SETTING: Catchment area of the Edinburgh otolaryngological unit. PARTICIPANTS: 289 General practitioners who responded to the survey; 21 outpatients in the ear, nose, and throat department with occlusive wax. RESULTS: 274 General practitioners removed wax by syringing, but only 53 (19%) always performed the procedure themselves; the remainder routinely delegated the task to practice nurses, some of whom had received no instruction. Ears were rarely examined again after the procedure. Complications had been experienced by 105 practitioners (38%) and included perforation, canal lacerations, and failure of wax removal. The removal of occlusive wax improved hearing by a mean of 5 dB over the frequencies analysed. CONCLUSIONS: About 44,000 ears are syringed each year in the area and complications requiring specialist referral are estimated to occur in 1/1000 ears syringed. The incidence of complications could be reduced by a greater awareness of the potential hazards, increased instruction of personnel, and more careful selection of patients. PMID- 2271825 TI - Psychological disturbance in children with haemophilia. AB - OBJECTIVE: To assess the need for formal psychotherapeutic intervention in children attending a children's haemophilia clinic after some of them had been diagnosed as positive for HIV. DESIGN: Comparison of haemophiliac children with matched control groups of diabetic and healthy children. SETTING: The West of Scotland Children's Haemophilia Centre, Glasgow. PATIENTS: 43 Children aged 3 to 16 years with mild, moderate, and severe clotting disorders were matched with control groups of 46 diabetic children and 42 physically healthy children. INTERVENTIONS: Parents of children aged 3-5 years were interviewed with the behaviour screening questionnaire. Children aged 6 to 16 were assessed by parental and teacher report using standardised questionnaires and self report using a computerised depression inventory. All were scored numerically according to the presence of symptoms of emotional and behavioural problems. MAIN OUTCOME MEASURES: The groups were compared for mean scores on each rating device and for number of children achieving scores within the pathological range. RESULTS: In the 6-16 age group five haemophiliac children, five diabetic children, and three healthy children scored in the pathological range on the parent questionnaire, as did two, three, and five respectively on the teacher questionnaire and four, four, and eight on the depression inventory. There was no significant difference across the three groups. Analysis of mean scores similarly showed no significant difference across groups. In contrast, the single measure used for younger children showed an increase in behavioural difficulties among the diabetic children. CONCLUSION: Haemophiliac children attending the West of Scotland Centre were no more disturbed than their diabetic or healthy peers despite the identification of HIV infection within the clinic and the widespread adverse publicity associated with AIDS and HIV infection. PMID- 2271826 TI - Increased energy expenditure in Parkinson's disease. PMID- 2271827 TI - Retinoblastoma in grandchildren of workers at Sellafield nuclear plant. PMID- 2271828 TI - How to choose a new partner in general practice. AB - OBJECTIVE: To provide a guide to choosing a new partner in general practice by using psychometric assessments. DESIGN: A descriptive account of the experience of one practice. SETTING: A general practice in Bristol. RESULTS: The partners found that using a psychologist to assess both themselves and the candidates facilitated the selection process. During the pre-interview stage the partners learnt about the dynamics of the practice and their own personalities. The examination of the candidates by an outside assessor as well as the partners gave a sense of security and a certainty that mistakes were unlikely to be made. CONCLUSION: More practices should consider adopting a selection process using psychometric assessments when appointing a new partner. PMID- 2271830 TI - Dentures. PMID- 2271829 TI - What information for the patient? Large scale pilot study on experimental package inserts giving information on prescribed and over the counter drugs. AB - OBJECTIVE: To compare the acceptability and the degree of understandability of two drug information leaflets on three over the counter and two prescribed drugs. DESIGN: Prospective observational study. SETTING: Random sample of municipal pharmacies throughout Italy. SUBJECTS: A total of 6992 clients of the pharmacies who requested the study drugs over a period of four months. INTERVENTION: Exposure of patients to two information leaflets, one approved by the Ministry of Health, and the other an experimental sheet prepared by the research working group. MAIN OUTCOME MEASURES: The degree of acceptability of the information was assessed by using a pretested questionnaire. Comments concerning information needs were also encouraged and collected. RESULTS: 6992 Clients responded to the questionnaire. Non-metropolitan (urban and rural) areas had the highest rate of participation. The participants strongly preferred the experimental leaflets to the approved leaflets, both with respect to accessibility of the contents (overall preference 78.1% v 17.8%) and ease of understanding the contraindications of drug use (90.2% v 73.7%). Basic attitudes related to the use of written information were similar among clients of different age groups, educational levels (though emerging people with primary school or lower educational levels showed slightly lesser understanding), and geographic areas. Up to 50% of those who took over the counter drugs indicated a disposition to change their drug seeking behaviour on the basis of the information in the experimental leaflet. The comments provided a useful complementary set of data on the information needs expressed by participants. CONCLUSIONS: The results of this pilot study indicate that patients will enter active programmes to investigate the provision of problem oriented drug information. Their information needs seem to concern both prescribed and over the counter drugs. More extensive and systematic work is required to develop an improved consumer oriented language for widely used drugs. PMID- 2271831 TI - NHS profile. Enter the men from the Audit Commission. Interview by Richard Smith. PMID- 2271832 TI - Cross contamination of bronchial washings. PMID- 2271833 TI - Too many ethical committees. PMID- 2271834 TI - Preventing heart disease. PMID- 2271835 TI - Guidelines for management of asthma. PMID- 2271836 TI - Preimplantation genetic diagnosis. PMID- 2271837 TI - Reformulation of injectable vitamin A. PMID- 2271838 TI - Do streptococci cause toxic shock? PMID- 2271839 TI - Bacteria and arthritis. PMID- 2271840 TI - Crutches. PMID- 2271841 TI - Detecting bladder cancer. PMID- 2271842 TI - Potassium and magnesium in essential hypertension. PMID- 2271843 TI - Tubal pregnancy. PMID- 2271844 TI - Medicine in the armed services. PMID- 2271845 TI - Surely a natural cancer remedy can't be dangerous. PMID- 2271846 TI - Toxic epidermal necrolysis associated with indapamide. PMID- 2271847 TI - Cholestasis associated with cinnarizine. PMID- 2271848 TI - We cannot afford an AIDS epidemic. PMID- 2271849 TI - Children with head injuries. PMID- 2271850 TI - New directions in primary biliary cirrhosis. PMID- 2271851 TI - Accident and emergency services. PMID- 2271852 TI - Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study. AB - OBJECTIVE: To find out whether a 10-14 days' course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN: Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING: Departments of infectious diseases in three hospitals in Linkoping, Malmo, and Stockholm, Sweden. PATIENTS: 40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS: 20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks' observation. MAIN OUTCOME MEASURES: Arthritic symptoms assessed clinically and by using Ritchies' index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS: No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION: Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection. PMID- 2271853 TI - Effect of thiazide on rates of bone mineral loss: a longitudinal study. AB - OBJECTIVE: To determine the effect of thiazide diuretic drugs on rates of bone mineral loss. DESIGN: Longitudinal, observational study with a mean follow up of five years. SETTING: Hawaii Osteoporosis Center, Honolulu. SUBJECTS: 1017 Japanese-American men born between 1900 and 1920, of whom 378 were treated for hypertension (study group) and 639 did not have hypertension (control group). INTERVENTION: Thiazide diuretics were taken by 325 men for a mean of 11.9 years; 53 men took antihypertensive drugs other than thiazides. MAIN OUTCOME MEASURE: Rate of bone loss estimated from serial photon absorptiometric scanning at three skeletal sites (calcaneus, distal radius, and proximal radius). RESULTS: Rates of bone loss at all three sites were significantly reduced among thiazide users when compared with controls. The reductions in loss rate ranged from 28.8% (p = 0.02) (distal radius) to 49.2% (p = 0.0005) (calcaneus) relative to the controls. At all three sites the men taking other antihypertensive drugs had faster loss rates (22.6-43.1%) than those of the controls but the difference was significant only for the distal radius. CONCLUSION: Thiazide diuretics slow the rate of bone loss in elderly men. PMID- 2271855 TI - Patients' self administration of hydrocortisone. PMID- 2271854 TI - Inappropriate use of laboratory services: long term combined approach to modify request patterns. AB - OBJECTIVE: To see whether changes in request patterns for haematological tests could be influenced in the long term by information released from a haematology department. DESIGN: Analysis of request patterns by hospital divisions before and after intervention and of costs of intervention and savings achieved. SETTING: Haematology laboratory of an inner city district general hospital. INTERVENTIONS: Monthly release of a comparison of clinicians' workload statistics, issue of on call guidelines, and promulgation of information (by seminars and factsheets) on appropriate use of tests. MAIN OUTCOME MEASURES: Request patterns before and after intervention. RESULTS: During the year after intervention requests fell by at least a fifth, and the reduction persisted over the next two years. The reduction was most pronounced in relation to inpatients within the division of medicine, for whom requests fell from an average of 4.0 per patient in the six months before intervention to 2.9 per patient in the six months after. CONCLUSIONS: A definite and sustained reduction in inappropriate requests for laboratory investigations may be achieved by an ongoing policy of intervention including issuing guidelines and factsheets and holding seminars, but a positive attitude among senior consultant staff is crucial. PMID- 2271856 TI - Hypoalbuminaemia after prolonged treatment with recombinant granulocyte macrophage colony stimulating factor. PMID- 2271857 TI - Response by women aged 65-79 to invitation for screening for breast cancer by mammography: a pilot study. AB - OBJECTIVE: To determine whether there is sufficient benefit to be gained by offering screening for breast cancer with mammography to women aged 65-79, who are not normally invited for screening. DESIGN: Pilot study of women eligible for screening but not for personal invitation. The results of this study were compared with the results of routinely screened younger women (aged 50-64) from the same general practice. SETTING: One group general practice in south Manchester. PATIENTS: The 631 women aged 65-79 on the practice list. A total of 42 (7%) were excluded by the general practitioner, and 22 (4%) invitation letters were returned by the post office. MAIN OUTCOME MEASURES: Response rates to invitation for screening assessed by three indices: crude population coverage ratio, crude invited population coverage ratio, and corrected invited population coverage ratio. RESULTS: 344 Patients aged 65-79 (61% of those invited, excluding those who could not be traced) were screened compared with 77% of women aged 50 64. The three response indices were higher for younger women than older: crude population coverage ratio = 66.5%, crude invited population coverage ratio = 69.3%, corrected invited population coverage ratio = 76.8% for women aged 50-64, compared with 54.5%, 58.4%, and 60.7% respectively for women aged 65-79. All four biopsies done in the older women gave positive results, giving a cancer detection rate of 11.6/1000 compared with 4.1/1000 among younger women. CONCLUSIONS: These results show that there is a potential for high attendance at routine screening by older women if they are invited in the same way as younger women. If these results are found elsewhere the costs and benefits of screening older women should be reassessed. PMID- 2271858 TI - Has adjuvant treatment of breast cancer had an unfair trial? PMID- 2271859 TI - Trusses. PMID- 2271860 TI - Doctors and benefits. PMID- 2271861 TI - Disseminated actinomycosis. PMID- 2271862 TI - Toxic dilatation of the colon in shigellosis. PMID- 2271863 TI - Acid suppression. PMID- 2271864 TI - Carbon monoxide poisoning in the home. PMID- 2271865 TI - Retreat from medicine. PMID- 2271866 TI - Recognising pseudo-seizures. PMID- 2271867 TI - Plastic bullets in Northern Ireland. PMID- 2271868 TI - Trauma in pregnancy. PMID- 2271869 TI - A painful process. PMID- 2271870 TI - Do streptococci cause toxic shock? PMID- 2271871 TI - Consenting patients. PMID- 2271872 TI - HIV infection and foreign travel. PMID- 2271873 TI - Biopsy of abdominal masses guided by ultrasound. PMID- 2271874 TI - Problems of developing countries. PMID- 2271875 TI - Tubal pregnancy. PMID- 2271876 TI - Referral rates for colposcopy. PMID- 2271877 TI - An integrated child health service. PMID- 2271878 TI - Cultured composite skin grafts for burns. PMID- 2271879 TI - Does passive smoking cause heart disease? PMID- 2271880 TI - Does treatment for cervical intraepithelial neoplasia affect fertility and pregnancy? PMID- 2271881 TI - Male rape. PMID- 2271882 TI - A fresh start for health. PMID- 2271883 TI - Abuse of elderly people by their carers. AB - OBJECTIVE: To assess the prevalence of abuse of elderly people by their carers and the characteristics of abusers and the abused. DESIGN: Information on abuse and risk factors was collected over six months from carers and patients. Risk factors were identified in the abused group and compared with those in a non abused control group. SETTING: Carers were interviewed at home; patients were examined in the wards of Putney and Barnes geriatric hospitals, London. SUBJECTS: All patients referred from any source for respite care to the geriatric services over a six month period and their carers. MAIN OUTCOME MEASURES: Amount of physical and verbal abuse or neglect. Quantification of risk factors and correlation with the presence or absence of abuse. RESULTS: 45% Of carers openly admitted to some form of abuse. Few patients admitted abuse. The most significant risk factor for physical abuse was alcohol consumption by the carer (p less than 0.001). Other significant risk factors were a poor pre-morbid relationship and previous abuse over many years. Abuse was often reciprocated and was associated with social dysfunction in many patients. Service delivery, respite care, and level of mental and physical disability were not significantly associated with abuse. CONCLUSION: The high level of abuse found in elderly patients in respite care was particularly associated with alcohol abuse and long term relationships of poor quality, which are difficult to change. Even with increased provision of services, care in the community may not be the best solution for these people. PMID- 2271884 TI - "Vanishing" of vertebra in a patient with sickle cell haemoglobinopathy. PMID- 2271885 TI - Colour coded duplex sonography in suspected deep vein thrombosis of the leg. PMID- 2271886 TI - Are falls from supermarket trolleys preventable? PMID- 2271887 TI - Obstetric audit using routinely collected computerised data. AB - OBJECTIVE: To examine the use of routinely collected computerised data in clinical audit. DESIGN: Retrospective review of all analyses of obstetric practice based on a computerised data system from January 1983 to June 1988. SETTING: Maternity department of the regional referral hospital in Oxford. MAIN OUTCOME MEASURES: Congruence with the principles of clinical audit; that is, comparing clinical practice with previously agreed standards and changing practice to meet these standards if necessary. RESULTS: Over the five and a half years of the study the data formed the basis of 130 special inquiries into different aspects of obstetric practice. Most inquiries seemed to be aimed only at describing current activities and identifying trends. Genuine clinical audit was rare. Simple audits--for example, concerning induction for pregnancy after term--could be supported by the computerised data, but for detailed and wide ranging audits--for example, reducing antenatal clinic visits for low risk multiparas--the data had to be supplemented from other sources. CONCLUSIONS: Routinely collected computerised data enable ongoing clinical audit, but it becomes a reality only when clinicians agree on standards of practice and have a flexible attitude towards change. Even then, genuine clinical audits of obstetric practice demand more detailed and comprehensive data than are generally available on such systems. PMID- 2271888 TI - Algorithm based improvement of clinical quality. PMID- 2271889 TI - NHS review. Kenneth Clarke: hatchet man or remoulder. Interview by John Roberts. PMID- 2271890 TI - Introduction to the social security system. PMID- 2271891 TI - Milk for babies and children. PMID- 2271892 TI - Sexual expression in paraplegia. PMID- 2271893 TI - The mean predicts the number of deviants. PMID- 2271894 TI - Preventing heart disease. PMID- 2271895 TI - Psychological outcomes in women with early breast cancer. PMID- 2271896 TI - HIV and surgeons. PMID- 2271897 TI - Diarrhoea as a side effect of digoxin. PMID- 2271898 TI - Pruritus ani, piperazine, and thrombocytopenia. PMID- 2271899 TI - Effect of streptozotocin-diabetes on rat liver asialoglycoprotein receptor turnover: in vivo degradation and in vitro biosynthesis. AB - The metabolic turnover of the Hepatic Binding Protein (HBP) was investigated in streptozotocin-diabetic rats. We have already shown that diabetes induced a decreased ligand binding capacity while the immunoreactive HBP was normal. To explore the eventual modifications due to diabetic state upon the turnover of HBP, we followed the in vivo degradation of HBP and its biosynthesis in vitro. After in vivo labelling with L-[3H] leucine and purification of HBP from rat livers, we found a 20% decrease in diabetic HBP half-life. By in vitro incubations of freshly isolated hepatocytes and a 2 h-pulse in the presence of L [35S] methionine, we showed that diabetes provokes an increased uptake of L-[35S] methionine in hepatocytes allowing an augmented synthesis of HBP although the L [35S] methionine incorporation into total proteins was less efficient. PMID- 2271900 TI - Distribution of sugar-binding sites within interphase nuclei and mitotic chromosomes of a human cell line. AB - Using gold labelled neoglycoproteins containing either alpha-D-glucose, N-acetyl beta-D-glucosamine, alpha-D-mannose, 6-phospho-alpha-D-mannose, and alpha-L fucose (BSA), we investigated their intranuclear binding sites in the TG human cell line. Although gold-labelled BSA did not give any noticeable labelling, the presence of 1% free BSA in the medium containing the gold labelled neoglycoproteins was revealed to be a key factor of the labelling. During interphase in the presence of free BSA most of the labelling was detected in the nucleoplasm. The border of the condensed chromatin, known to be the site of hnRNA synthesis as well as the interchromatin areas enriched in RNPs were labelled. Condensed chromatin also contained binding-sites. The nucleolus was seen to present low labelling in comparison with the labelling observed over the nucleoplasm. These nucleolar binding sites were located both in the dense fibrillar and granular components. No labelling could be detected over the fibrillar centers which are very conspicuous in this cell line. During mitosis sugar-binding sites were observed over the chromosomes. Data reported here show for the first time that lectin-like proteins and chromatin components are colocalized both during interphase and mitosis. In addition, within the nucleolus the presence of sugar-binding proteins was seen to be restricted to the dense fibrillar and granular components. PMID- 2271901 TI - Expression of liver peroxisomal proteins as compared to other organelle marker enzymes in rats treated with hypolipidemic agents. AB - Peroxisome proliferation induced by 2 hypolipidemic agents (clofibrate and ciprofibrate) was studied in rats by complementary approaches, ie cell fractionation, electron microscopy, marker enzyme activities, immunoblotting and nucleic acid hybridization techniques. Administration of clofibrates for 2 and 52 weeks in doses of 500 ppm and 50 ppm respectively, or ciprofibrate for 2,28 and 52 weeks in doses of 250, 25 and 25 ppm respectively, did not alter the behavior of the peroxisomes after induction as shown by ultracentrifugation profiles. The peroxisome mass was increased as shown by the purification procedure. Specific enzymes (catalase and mostly cyanide insensitive palmitoyl CoA oxidase) were induced. A mechanism of peroxisome biogenesis might have been initiated ie cytosolic factor, ligand-receptor interaction and/or post-translational modification of the import. Increase in marker enzyme activities showed that the peroxisomes are the most responsive organelles in comparison to lysosomes, mitochondria and smooth endoplasmic reticulum (except for cytochrome P-450 LA omega-hydroxylase). Peroxisomal integral membrane proteins appeared to be differently induced: some of them were virtually absent in untreated rat liver but were strongly expressed in treated liver. Induction was sustained for 52 weeks, indicating that there was no compensatory mechanism. PMID- 2271902 TI - Characterization of human autoantibodies specific for lamin A. AB - We have characterized human autoimmune polyclonal antibodies reactive with lamin A, a 74 kDa peripheral protein of the nuclear envelope. Unlike other known antibodies to lamin A, the antibodies described here do not crossreact with the structurally related lamin C. These antibodies feature only chi light chains suggesting that their specificity is restricted to a limited number of epitopes. Based on the known amino acid sequence of human lamins A and C, the epitope(s) are most likely located in the 80 amino acid carboxyl tail of mature lamin A. PMID- 2271903 TI - Effects of local anaesthetics (lidocaine) on the structure and function of ciliated respiratory epithelial cells. AB - Sampling for nasal or bronchial ciliated cells requires the use of anaesthetic agents, but such drugs may interfere with the morphological or functional results. Lidocaine is the most frequently used local anaesthetic. In order to study the morphological and functional effects of lidocaine hydrochloride, we designed an experimental study on ciliated cells from guinea pig and bovine trachea. On guinea pig tracheal specimens, different lidocaine concentrations (0.05, 0.25 and 1%) were tested. Tracheal rings were immersed in either culture medium alone (control) or in different lidocaine concentrations. Measurements of ciliary beat frequency (CBF) were performed by the stroboscopic method. Tracheal rings were consecutively incubated in culture medium alone and a second set of measurements was performed. Tracheal rings were studied by light microscopy after incubation in either 1% lidocaine or in culture medium alone. On bovine tracheal specimens, a cotton wool swab impregnated with different lidocaine concentrations (0, 0.25, 1, 2.5 and 5%) was placed in contact with the tracheal mucosa. Three different kinds of samples were collected: the first one was used to study CBF, the second one (0.1 and 5%) was studied by scanning electron microscope (SEM) and the third (0.1 and 5%) by transmission electron microscopy (TEM). The results on guinea pig specimens show a significant but reversible CBF diminution for concentrations of 0.25 and 1% lidocaine and cellular lesions for the concentration of 1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271904 TI - Bovine spongiform encephalopathy (BSE): menace or mirage? PMID- 2271905 TI - Anaesthesia for small animal patients with neuromuscular disease. PMID- 2271906 TI - Cytogenetic studies in a canine neurofibroma. AB - An 11-year-old German shepherd bitch developed a neurofibroma in the right shank. On cytogenetic analysis of the tumour cells 90% presented themselves with trisomy 2, a derivative chromosome 13 (der13) and centric fusions 10/35 and 24/31. PMID- 2271907 TI - A routine 20-22 days post-service milk progesterone monitoring in dairy cows. Economic evaluation. AB - Three hundred and sixty inseminated Holstein cows were monitored in a controlled trial for low milk progesterone concentration 21-23 days post-breeding. Information about low progesterone cows was given to herdsmen for the experimental group only. Of the cows in the experimental group with milk progesterone of less than or equal to 4.5 ng/ml, 56.0% were inseminated within 2 days of monitoring compared to 28.8% of the control animals. Of the cows reaching the 42-day rectal pregnancy diagnosis, 13.7% and 43.6% were negative for the experimental and the control groups respectively. Inter-service intervals were 34.5 +/- 14.5 days and 44.3 +/- 17.7 days for the experimental and control groups respectively. Pregnancy rates were the same for 264 cows served on routine progesterone monitoring and for 318 cows bred on behavioural oestrus when matched to farm and day of breeding. A gain of US $32.5 (an equivalent of 85 l milk) per lactation for a cow in the monitored herd was established using the data in a model of a 250-cow herd with a total pregnancy goal of 82.4%. PMID- 2271908 TI - A method of assessing auditory and brainstem function in horses. AB - Brainstem auditory evoked potential (BAEP) waveforms were recorded as a means of objectively evaluating auditory and brainstem function in horses. BAEP recordings were readily and repeatably recorded from horses, under minimal restraint, using signal averaging equipment. Clearly identified BAEP waveforms were obtained with compression clicks of 30-100 dB (HHL) at 10 Hz applied in the external auditory meatus of one ear and masking white noise (10 dB lower) in the other ear. Vertex positive (upwards) waveforms I through V were obtained with an active, subdermal electrode over the ipsilateral and contralateral zygomatic processes of the temporal bones and the reference electrode over the vertex. Recording sweep duration was 10 ms, amplifier sensitivity 10 microV/division, display gain x 10 and low and high amplifier filters set at 200 Hz to 2 kHz. Such recordings can be useful in evaluation of all clinical cases suspected of showing degrees of deafness, vestibular disease or brainstem disease, and in monitoring the progress of such cases. PMID- 2271909 TI - The influence of a low cobalt intake on the neutrophil function and severity of Ostertagia infection in cattle. AB - Two trials involving housed cattle examined the effect of Co depletion and supplementation on immune status as assessed by the neutrophil function test which measures the ability of isolated neutrophils to kill the yeast Candida albicans. A third trial investigated the extent to which Co status influenced the severity of Ostertagia ostertagi infection. In the first two trials liveweight gains were unaffected until some 40-60 weeks on the low dietary Co intake despite very low serum vitamin B12 values being recorded after 10 weeks. However, the immune status as measured by the neutrophil function test was reduced within 10 weeks of commencing the low Co diet. On administration of Ostertagia ostertagi larvae, Co-depleted cattle showed a greater weight loss than Co-supplemented cattle but showed no difference in the length of the prepatent period, worm egg production or serum gastrin and pepsinogen concentrations. After anthelmintic treatment both groups showed a similar response. It is postulated that the lowered immune response of Co-depleted cattle resulted in the greater severity of the Ostertagia ostertagi infection. PMID- 2271910 TI - Cortisol in pregnancy toxaemia of sheep. AB - Of 31 pregnant ewes with clinical signs of pregnancy toxaemia, 24 had hypoglycaemia and hyperketonaemia at the time that a single blood sample was obtained. Twenty-five of these had a plasma cortisol concentration in excess of 10 ng/ml and six had a value below this. All the seven animals which did not show both hypoglycaemia and hyperketonaemia had a plasma cortisol concentration in excess of 10 ng/ml. Taking all the sheep together, 80% had a high plasma cortisol concentration. This could be the consequence of increased adrenal output or reduced excretion by the liver. PMID- 2271911 TI - Changes in liveweight gain, blood constituents and worm egg output in goats artificially infected with a sheep-derived strain of Haemonchus contortus. AB - Two groups of goats were dosed with 10,000 and 20,000 sheep-derived strain (SDS) larvae of Haemonchus contortus respectively. Over a period of 42 days goats dosed with 20,000 larvae lost more weight than those dosed with 10,000 larvae. Infected goats showed anaemia from about 2 weeks after infection as well as reduced levels of total serum proteins and albumins. PMID- 2271912 TI - Obligately anaerobic bacterial species isolated from foot-rot lesions in goats. AB - Lesions showing clinical signs of foot-rot from 120 goats were cultured on six selective media during October 1987 to November 1988. A total of 582 strictly anaerobic microorganisms belonging to 50 different species was isolated and identified. The anaerobes most frequently isolated belonged to the following genera: Bacteroides (80%), Peptostreptococcus (63.6%), Megasphaera (40%), Fusobacterium (29.2%), Clostridium (22.5%), Propionibacterium (12.5%), Eubacterium (11.7%) and Leptotrichia (10.8%). Percentages for Acidaminococcus, Peptococcus, Tissierella, Wolinella and Veillonella were below 10%. The following species were identified in 10% or more of cases: Peptostreptococcus anaerobius (61.7%), Bacteroides buccae (51.7%), Bacteroides nodosus (42.5%), Megasphaera elsdenii (40%), Bacteroides ruminicola subsp. brevis (22.5%), Fusobacterium necrophorum (19.2%), Leptotrichia buccalis (11.7%) and Clostridium perfringens (10%). Lower percentages were obtained for the remaining species. The efficiency and selectivity of the six culture media used for isolation are discussed. PMID- 2271913 TI - Milk progesterone determination in buffaloes post-insemination. AB - Milk progesterone levels were studied in 17 buffaloes between post-insemination and 30 days thereafter. Six animals were confirmed pregnant. Seven of 10 animals took greater than 24 days to return to oestrus and the pattern of change of progesterone levels indicated a steady increase from 1 ng/ml on day 2 to 20 ng/ml on day 14 post-insemination, falling subsequently to about 5 ng/ml, 2 days prior to oestrus. In pregnant buffaloes, the milk progesterone levels showed a continuous increase up to 20 days post-insemination but did not decline thereafter. In individual buffaloes returning to oestrus, a cut-off milk progesterone level of greater than 10 ng/ml was considered for pregnancy diagnosis, 20, 22 and 24 days post-insemination. The test was 60, 75 and 75% accurate for detection of pregnancy on days 20, 22 and 24 respectively and 100% for non-pregnancy diagnosis on all three days. Individual animals showed a highly variable oestrous cycle length, which has been suggested as a contributory factor for false pregnancy diagnosis by milk progesterone test in this species. Milk progesterone assay may also identify silent heats, and clinical disorders. PMID- 2271914 TI - Development of a simple, direct, microtitre plate enzymeimmunoassay (EIA) for progesterone determination in whole milk of buffaloes. AB - A method of estimating progesterone in buffalo whole milk by EIA using progesterone 6 beta-OH-hemisuccinate-horseradish peroxidase as the enzyme label and an antiserum raised against progesterone-7 alpha-carboxyethyl-thioether-BSA was developed. The microtitration plates used in the assay were first coated with affinity purified sheep IgG developed against rabbit IgG. The immune reaction was performed by incubating a mixture of 1 microliter of whole milk (diluted to 20 microliters with assay buffer), 100 microliters of enzyme label and 100 microliters of antiserum for 90 min in the dark. After washing the plates, 150 microliters of the substrate solution was added. The mixture was incubated in the dark for 40 min before the reaction was stopped and the optical density was measured at 450 nm. The calibration curve was sensitive in the range 0.8-40 pg/well, corresponding to 0.8-40 ng/ml. Milk samples from cycling buffaloes were tested for progesterone concentration by running parallel EIA and RIA. A good correlation of 0.91 was obtained and the estimated values were similar using both techniques. The method has demonstrated about 10 times greater sensitivity than RIA in buffalo milk. PMID- 2271915 TI - Role of oxytocin and/or PGF2 alpha on breeding efficiency in buffaloes. AB - A study was conducted on 40 buffalo-cows, assigned randomly, immediately after calving into three groups: group I (n = 10) injected with saline and taken as control; group II (n = 15) received 25 mg PGF2 alpha/animal (Lutalyse); group III (n = 15) received 25 mg PGF2 alpha + 25 i.u. oxytocin/animal (Syntocinon), single i.m. dose. Oxytocin and/or PGF2 alpha significantly (P less than 0.01) shortened the interval from calving to first service (38.33 and 31.53 days for groups II and III respectively, versus 91.60 days for controls). The treatment reduced the service period (38.29 and 35.87 days for groups II and III respectively, versus 45.40 days for controls). Concomitantly a significant (P less than 0.01) decrease in the open-days post partum was achieved (76.62 and 67.40 days for groups II and III respectively, versus 137.00 days for controls). In addition, the treated buffaloes needed significantly (P less than 0.01) fewer services per conception (1.67 and 1.20 S/C for groups II and III respectively) than the untreated ones (2.70 S/C), besides a substantial improvement (P less than 0.01) in their conception rate either at 60 or 85 days post partum. Significantly improved (P less than 0.05) results were obtained in the oxytocin and PGF2 alpha treated animals, than in those receiving PGF2 alpha alone for all the previous parameters, except for the service period. Buffaloes therefore seemed to respond better to such treatment than dairy cows. PMID- 2271916 TI - Ontogeny and phylogeny: a re-evaluation of conceptual relationships and some applications. AB - The history of biology reveals numerous interpretations of the relationship between ontogeny and phylogeny, among them Garstang's critical realization that phylogeny can only be the history of changes in an ancestral ontogeny. One extrapolation of Garstang's conclusion is that the study of phylogeny should involve comparisons of ontogenies, in order to allow a reconstruction of the sequence of changes that led to the present variation in these ontogenies as well as the mechanisms underlying these changes. It is suggested that this can be done by recognizing homologous developmental stages among various ontogenies and subjecting these stages to a cladistic analysis. Some of the problems involving such analysis are explored in the course of examining the phylogeny of pharyngeal pouch ontogenies as a model system. It is concluded that sequences of ontogenetic stages are conserved (von Baerian recapitulation) but that terminal (Haeckelian recapitulation) and nonterminal alterations in the ancestral ontogeny are frequent. Both terminal and nonterminal alterations occur with approximately equal frequency in the case of pharyngeal pouches, but non-terminal deletion is rare to nonexistent. Examination of two additional morphological cases in which ontogeny has been utilized to infer phylogenetic changes-ontogenetic parcellation of neural systems and craniate head organization-reveals a number of problems from the point of view of a cladistical analysis of ontogenesis. Ontogenetic parcellation is essentially a recasting of Haeckel's biogenetic law and is rejected on the grounds that ontogenies do not parallel phylogenies, and only primitive and derived characters, not organisms, can be recognized. It is argued that the phylogenetic significance of transient neural characters can be determined only within a cladistical context and that insufficient ontogenetic data presently exist to evaluate most characters. Finally, the history of current models of craniate head organization is traced, and this information, along with that from more recent developmental studies, necessitates rejection of the Goodrich and Jarvik-Bjerring models. A new model is presented that purports to incorporate current ideas of somitomere and neuromere distribution, but it is deemed inadequate because, like previous models, it is based on information gleaned primarily from the ontogeny of a single species, whereas the model sought is a model of the ontogeny of ancestral craniates. To arrive at such a model, we must generate a morphotype, based on shared primitive features of cephalic ontogenies of all craniate radiations, which involves a cladistic analysis of these ontogenies. PMID- 2271917 TI - Evolutionary innovation in behavior and speciation: opportunities for behavioral neuroethology. AB - Populations of animals differentiate by speciation. How speciation takes place, for long a puzzle for evolutionary biologists, should be regarded as a research opportunity for neuroethologists and comparative behaviorists. It is now clear that behavior may play an important part in the process of speciation. The existence of sexually dimorphic anatomy and behavior in many animals has provided a rich subject for investigation by comparative neurobiologists and behaviorists, who emphasize analysis of proximate mechanisms that generate dimorphism in phenotype. However, sexual dimorphisms also figure prominently in the theory of sexual selection. Sexual selection is viewed as a primary behavioral mechanism in the process of speciation. Some examples of 'explosive' speciation are presented, and the putative role that sexual selection plays in these cases is reviewed. A consideration of any evolutionary selective process must include genetics, and I will briefly summarize studies that indicate that even complex behavioral systems such as sexual selection, which sociobiologists refer to as a 'strategy', can have a relatively simple genetic basis. PMID- 2271918 TI - Neuroethological approaches to the evolution of neural systems. AB - Over the past two decades, neuroethologists have been unravelling the neural circuitry underlying some of the specialized capabilities animals use to obtain and process sensory information. Explicitly comparative studies of these systems can now be carried out to ask questions about the processes of evolutionary change in neural systems. In some cases, it can be seen how relatively minor modifications of neural networks may significantly expand the efficacy of sensory processing. Other comparative studies might ask whether expanding the number of steps involved in neural computation, or the area devoted to the representation of a particular sub-modality, constrains neural architecture in predictable ways. PMID- 2271919 TI - Brains, bodies and metabolism. AB - The interrelationship of brain and body sizes has been the subject of investigations for over a hundred years. These studies have demonstrated that variation in brain weights is much smaller than that in body weights; consequently, scaling studies are ones of negative allometry. Furthermore, the variability in brain weight is greater when comparisons are between species rather than among individuals of the same species, and the degree of variability in brain size differs among orders. The largest shifts in brain sizes relative to changes in body weights are found when comparing different ontogenetic stages. Debate continues as to the importance of metabolism in determining the interrelationship of brain-body weights for interpreting differences in relative brain size. Although past advances in the study of brain-body size associations have come by increasing the size of the data bases and by improved statistical analyses, the recent utilization of transgenic animals may provide new insights into the mechanism of this association. PMID- 2271920 TI - Comparative neurobiology: problems for a new decade. First annual Karger Workshop. Phoenix, AZ., October 28, 1989. Proceedings. PMID- 2271921 TI - Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease. AB - The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease. PMID- 2271922 TI - 5-HT1 receptor binding sites in the guinea pig superior colliculus are predominantly of the 5-HT1D class and are presynaptically located on primary retinal afferents. AB - The superficial layers of the guinea pig superior colliculus are characterized by high densities of [3H]5-HT binding sites. We have chosen receptor autoradiography to establish the drug binding profile and the localization of these sites. The binding of [3H]5-HT to guinea pig superior colliculus was nearly completely blocked by drugs such as 5-carboxamido-tryptamine and yohimbine, but only slightly sensitive to the 5-HT1 receptor agonist 8-hydroxy-dipropylamino tetralin. 5-HT1C antagonists such as mesulergine or the beta-adrenergic receptor blocking compound SDZ 21-009 did not show any effect. The profile of the majority of these sites corresponds to that of 5-HT1D sites. Unilateral enucleation resulted in a nearly complete depletion of [3H]5-HT binding in the contralateral superior colliculus, whereas [125I]Bolton-Hunter-8-methoxy-N-propylaminotetralin binding sites, corresponding to 5-HT1A receptors, were preserved. These results indicate that 5-HT1D (and not 5-HT1A) receptors might be presynaptically localized on non-serotoninergic neuronal pathways. The guinea pig visual system may be a useful model for the study of the properties of these presynaptic 5-HT heteroreceptors. PMID- 2271923 TI - Extracellular ions during veratridine-induced neurotoxicity in hippocampal slices: neuroprotective effects of flunarizine and tetrodotoxin. AB - Veratridine, by blocking Na+ channel inactivation and shifting activation to more negative membrane potentials, causes Na(+)-influx and a persistent tendency for depolarization. Veratridine is neurotoxic to cultured neurones, and this neurotoxicity can be blocked by the class IV calcium antagonist, flunarizine. We were interested to know whether similar effects could be found in a functional differentiated tissue containing adult neurones and glial cells. We examined this in hippocampal slices using extracellular potential recordings and ion-selective microelectrodes sensitive to [Na+]o, [Ca2+]o and [K+]o. Veratridine blocked synaptic transmission in CA1, and induced several episodes of spreading depression (SD). This was followed by a long-lasting increase in [K+]o and a continuous decrease in [Ca+]o. Following veratridine exposure to hypoxia only revealed a small negative DC shift and small shifts in extracellular ions; indicating that the cells had lost the ability to maintain ion homeostasis before the hypoxia, and that veratridine had been neurotoxic. In hippocampal slices obtained from guinea pigs which had been pretreated with 40 mg/kg x 2 flunarizine orally the time before the first SD induced by veratridine was doubled. Although the ion shifts during the first SD were similar to controls, flunarizine reduced the time of recovery of [Ca2+]o, [K+]o and DC potential. The increase in [K+]o baseline and the massive decrease in [Ca2+]o baseline seen following the SDs in the solvent group were smaller in the flunarizine-treated slices. During the subsequent hypoxic period the negative DC shift was 8x larger in the flunarizine group, and the shifts in [K+]o, [Na+]o and [Ca2+]o were bigger. Tetrodotoxin also delayed the first SD during veratridine and increased the size of the DC shift during the subsequent hypoxic period. Both flunarizine and tetrodotoxin therefore protected adult brain tissue containing glia from the neurotoxicity of veratridine. These findings suggest that persistent Na(+)-influx and the consequent Ca2(+)-influx produce neurotoxicity, and that the ability to attenuate this neurotoxicity may be important in the mechanism of action of cerebroprotective drugs from different pharmacological classes. PMID- 2271924 TI - Correlations between unit firing and EEG in the rat olfactory system. AB - The olfactory EEG of awake animals displays oscillatory bursts of activity in the gamma- (30-100 Hz) range. The bursts are correlated with inflow of air over the receptor layer in the nose. None of the inputs to the cortices that display these oscillations carries periodic signals in the gamma-range. Thus these bursts are generated locally, either by neuronal feedback interactions or by coupling of oscillatory neurons. In the first case if the oscillations are generated by negative feedback, then two classes of cells must exist: excitatory neurons and inhibitory neurons with the same frequency of oscillation but with a quarter cycle phase lag by the inhibitory cells from the excitatory cells. On the other hand, if the EEG's result from coupling of cells that are intrinsically oscillatory, there should be a broad but monomodal distribution of phase values. In order to determine the origin of these bursts, we performed simultaneous recordings of EEG and multi-unit spikes in the 4 parts of the olfactory system (olfactory bulb, anterior olfactory nucleus, prepyriform cortex and lateral entorhinal area) of awake and motivated rats. For each sample, the EEG and the multi-unit spikes were recorded from the same local neighborhood. The multi-unit electrode recorded pulses from the principal output neurons of the respective cortical areas. In all locations tested, the oscillations in pulse probabilities of firing were found to have the same frequency as the dominant EEG frequency. In all 4 structures two sets of cells were found. One set displayed pulses in phase with the EEG and the other set displayed pulses that led or lagged the EEG by approximately 1/4 cycle. These data confirm the negative feedback interaction model rather than the coupled oscillator model for the generation of the bursts in the olfactory system. The relevance of these findings to other cortical systems, in casu the visual cortex is discussed. PMID- 2271925 TI - Rapid and localized alterations of neuropeptide Y in discrete hypothalamic nuclei with feeding status. AB - Neuropeptide Y (NPY) is believed to regulate the normal eating behavior and body weight in rats via central mechanisms. We have investigated whether NPY, which stimulates food intake, may in turn be modified by the nutritional state of the animals. Thus the impact of food deprivation (FD) (48 h) and subsequent refeeding on the levels of NPY in discrete hypothalamic areas was examined in this study. The results showed site specific change in only 3 of 7 hypothalamic sites. A 5 fold increment in NPY was reported in the paraventricular nucleus (PVN) and a 10 fold increase was observed in the arcuate nucleus-median eminence (ARC-ME). While subsequent refeeding for 6 h reversed the effect of FD in the ARC-ME, the levels of NPY in the PVN remained high in the refed rats. The perifornical lateral hypothalamus displayed a different pattern, namely, a significant increase in NPY content in refed as compared to satiated and deprived rats. The NPY levels in 4 other hypothalamic sites, namely, the dorsomedian, ventromedian, supraoptic and suprachiasmatic nuclei, and two extrahypothalamic sites, namely caudate nucleus and nucleus accumbens, showed total resistance to any change following deprivation and refeeding. These data emphasize the important and specific role of the paraventricular and arcuate nuclei in NPY's regulation of food intake and provide support for the idea that the variations of hypothalamic NPY after food deprivation reflect a specific physiological response of feeding regulatory system to alterations in the animal nutritional state and body weight. PMID- 2271926 TI - Expression of statin, a non-proliferation-dependent nuclear protein, in the postnatal rat brain: evidence for substantial retention of neuroglial proliferative capacity with aging. AB - Statin is a 57 kDa protein expressed in nuclei of reversibly and irreversibly growth-arrested (Go-phase) cells. In this report, immunohistochemical localization of statin in the developing and aging rat brain was achieved using the monoclonal antibody, S-44. On postnatal day 2, post-migratory neurons in the developing cerebral cortex were statin-positive. Many statin-negative cells were observed in the lateral subependymal zone of the lateral ventricle. By postnatal day 10, most neuronal nuclei were statin-positive although small numbers of statin-negative neurons were still encountered in the lateral subependymal zone and hippocampal dentate gyrus. At 3, 18 and 33 months, all neuronal nuclei surveyed were statin-positive. These results support the contention that, save for the postnatal persistence of 'germinal zones' such as the subependymal region and dentate gyrus, neuronal proliferation in the rat is largely completed by the time of birth. In striking contrast to neuronal statin expression, a significant fraction of neuroglia in both grey and white matter remains statin-negative at all ages examined. In the corpus callosum, 33.2%, 34.0% and 34.7% of glial nuclei were statin-negative at 3, 18 and 33 months, respectively. These findings indicate that: (i) even in senescent brain, the cycling (statin-negative) glial pool is substantially larger than previously surmised from S-phase labeling experiments; and (ii) during aging, the ratio of noncycling-to-cycling neuroglia remains very tightly regulated. Examination of other non-neuronal cell types revealed that most, if not all, ependymal and choroid plexus epithelial cells were statin-positive in the neonatal and adult brains in keeping with the predominantly prenatal proliferation of these tissues. Our results indicate that statin immunolabeling using the S-44 antibody is a powerful technique for the in situ identification of non-proliferating cells in the developing and aging nervous system. PMID- 2271927 TI - Respiratory and cardiovascular effects of tetrodotoxin in urethane-anesthetized guinea pigs. AB - Cardiorespiratory effects of tetrodotoxin (TTX) (15 micrograms/kg, i.p.) were investigated in urethane-anesthetized guinea pigs acutely instrumented for the recording of medullary respiratory-related units (RRUs), diaphragm electromyogram (DEMG), electrocorticogram (ECoG), electrocardiogram (ECG), blood pressure (BP), endtidal CO2, and arterial O2 and CO2. Respiratory system responses showed a hyperventilatory profile during the initial stage of intoxication. This was followed by an abrupt onset of a progressive decrease in the respiratory frequency, and a respiratory rate depression-related respiratory failure. The average time to TTX-induced respiratory arrest and death was 10.3 +/- 4.2 min. Concurrently recorded inspiratory and expiratory RRU activities indicated that respiration invariably failed in an end-expiratory position as manifested by a sustained period of expiratory RRU discharge. The progressive rate depression prior to respiratory arrest was temporally correlated only to a concomitantly augmenting expiratory RRU discharge duration. Inspiratory RRU discharge duration, on the other hand, did not display any significant change throughout the course of intoxication. The asymmetry in RRU response patterns indicates either an expiratory network component's particular sensitivity to perturbation by TTX or a dissociative trend in some bulbar respiratory rhythmogenic mechanisms. Peripheral cardiorespiratory changes were also quite profound. These included a gradual and steadfast decline in BP, a steadily decreasing amplitude in DEMG oscillations, and a state of progressive hypercapnia and hypoxemia. Changes in heart rate and ECG waveform attributes prior to respiratory arrest were not appreciable. In conclusion, in addition to a variety of TTX-induced peripheral cardiorespiratory effects, findings from this study have revealed a central respiratory system component that appears to show an unusual sensitivity to perturbation by TTX. The significance of this unique phenomenon as it relates to the nature and extent of TTX-induced central respiratory depression is discussed. PMID- 2271928 TI - Phenylephrine-induced antinociception: investigations of potential neural and endocrine bases. AB - Acute hypertensive states can produce antinociception, largely via unknown mechanisms. The aim of the present series of experiments was to examine potential hormonal and neural bases of analgesia induced by i.v. infusion of the pressor (hypertensive) agent phenylephrine. All rats were implanted with right jugular and left carotid cannulae for phenylephrine infusion and blood pressure/heart rate monitoring, respectively, and were tested approximately 24 h later in the unanesthetized state. The tail-flick test was used to measure responsivity prior to, during, and after phenylephrine infusion. Potential adrenal and pituitary contributions to phenylephrine-induced antinociception were examined, respectively, by physical disruption of adrenal blood flow and pharmacological suppression of pituitary activation. Acute block of all adrenal hormones, via closure at the time of testing of pre-implanted adrenal ligatures, did not block phenylephrine antinociception. However, pharmacological suppression of pituitary activation via pretreatment with the synthetic glucocorticoid dexamethasone abolished phenylephrine antinociception. Intriguingly, dexamethasone had no noticeable effect on urination prior to phenylephrine administration, yet only dexamethasone-treated rats exhibited copious urination during phenylephrine infusion. This suggests that the hypertensive agent phenylephrine releases vasopressin from the posterior pituitary terminals of the paraventricular hypothalamus (PVH) in a dexamethasone-suppressible manner, possibly via the known baroreceptor-nucleus tractus solitarius (NTS)-PVH link. Since (1) bilateral lesions of the spinal cord dorsolateral funiculus (DLF) were shown in the current study to abolish phenylephrine antinociception, (2) PVH is known to send vasopressinergic projections to the spinal cord via the DLF, and (3) intrathecal vasopressin produces antinociception via V1-like vasopressin receptors, the effect of an intrathecal V1 vasopressin antagonist was tested on phenylephrine induced antinociception. The V1 vasopressin antagonist blocked phenylephrine antinociception, suggesting that phenylephrine antinociception may be mediated by a baroreceptor-NTS-PVH-DLF circuit leading to vasopressin release at spinal levels. PMID- 2271929 TI - Effects of L-tryptophan and other amino acids on electroencephalographic sleep in the rat. AB - Electroencephalographic sleep was quantitated in adult male Sprague-Dawley rats following single injections of the methylesters of tryptophan, valine or alanine. The amino acids were administered at the onset of the daily light period (09.00 h); electrographic data were collected for the succeeding 6-h period. Saline served as the injection control, and fluoxetine, a serotonin-reuptake blocker, as a positive control. The injection of tryptophan methylester (125 mg/kg) caused a delay in rapid eye movement (REM) sleep onset, and significantly reduced the amount of REM sleep during the first 2 h postinjection. Tryptophan produced no effect on sleep onset, nor did it influence total sleep time. Fluoxetine (2.5 mg/kg) produced similar effects, as previously observed. The methylesters of valine and alanine were without effect on REM sleep, when injected at a molar dose equivalent to that for tryptophan. No consistent effects of any of the test substances were noted on non-REM (NREM) sleep or waking time, or on any of the other sleep indices quantitated. Together, the data indicate that tryptophan selectively reduces REM sleep; the effect is not due to a non-specific action of amino acids or their methylesters. The effect on REM sleep may be the consequence of a tryptophan-induced stimulation of 5-HT synthesis and release, since it is like that produced by fluoxetine, a drug that enhances transmission across serotonin synapses. PMID- 2271930 TI - Calbindin D28k-containing splanchnic and cutaneous dorsal root ganglion neurons of the rat. AB - Calbindin D28k (CaBP)-containing splanchnic and cutaneous sensory neurons in the rat dorsal root ganglia (DRGs) were investigated immunocytochemically in combination with a fluorescent dye tracer (Fluoro gold). About 15% of the DRG neurons at Th9-10 levels showed CaBP-like immunoreactivity. Eighty-four % of the splanchnic sensory neurons were immunoreactive to CaBP, while only 3% of the cutaneous sensory neurons were. The diameters of the splanchnic and cutaneous sensory neurons containing CaBP were 23.4 +/- 6.3 microns and 38.4 +/- 8.8 microns, respectively. Splanchnic sensory neurons containing CaBP were sensitive to capsaicin while cutaneous ones were not. These findings suggest that CaBP containing splanchnic and cutaneous sensory neurons constitute different subgroups among the DRG neurons at the lower thoracic level. PMID- 2271931 TI - Ethanol enhancement of a calcium-activated potassium current in an identified molluscan neuron. AB - The effects of ethanol (5-50 mM) on cell F1 in the right parietal ganglion of Helix aspersa were studied electrophysiologically. In normal physiological solution ethanol depressed both spontaneous action potential duration and frequency by enhancement of the repolarization and after-hyperpolarization phases respectively. Depolarization under voltage-clamp in Na-free solution produced an outward current which peaked at about 100 ms and decayed to 75% of peak by 250 ms. Variation of external K+ and Ca2+ concentrations and blockade of Ca current with Co2+ suggests that this current, which is increased by more than 50% with 5 mM ethanol, is a Ca-activated K current. These results add to evidence that a variety of ion channels, depending on cell type and conditions, are affected by pharmacologically relevant concentrations of ethanol. PMID- 2271933 TI - Monodendritic neurons: a cell type in the human cerebellar cortex identified by chromogranin A-like immunoreactivity. AB - The only perikarya expressing chromogranin A-like immunoreactivity in the human cerebellar cortex correspond with a cell type previously described in the rat. The name monodendritic cell is proposed for these neurons. PMID- 2271932 TI - Lesions producing REM sleep without atonia disinhibit the acoustic startle reflex without affecting prepulse inhibition. AB - This study determined whether the brainstem motor inhibition system that mediates muscle atonia during rapid eye movement (REM) sleep is involved in the elicitation and prepulse inhibition of the acoustic startle reflex. Electrolytic or neurotoxic (glutamate) lesions were made in the dorsolateral pontine tegmentum or the medial medulla, respectively, to produce the syndrome of REM sleep without atonia. Startle responses were released during REM sleep following the lesions. However, the amount of startle suppression produced by auditory prepulse after the lesion did not differ from that seen in intact controls. We conclude that REM sleep suppression of the acoustic startle responses is mediated by the system responsible for tonic motor inhibition, but auditory prepulse inhibition of the acoustic startle is not. PMID- 2271934 TI - Chronic testosterone propionate treatment decreases the concentration of [3H]quipazine binding at 5-HT3 receptors in the amygdala of the castrated male rat. AB - Chronic administration of testosterone propionate (TP) was found to decrease the concentration of [3H]quipazine binding at 5-HT3 receptors in the lateral and basal amygdaloid nuclei of the brains of castrated male rats. TP had no effect on the binding of [3H]quipazine at 5-HT3 receptors in the posterolateral or posteromedial cortical amygdaloid nuclei, or in the amygdalohippocampal areas. It is suggested that the effects of testosterone on sexual and other social behaviors in male rats may be mediated, at least in part, by decreases in the activation of 5-HT3 receptors in the amygdala. PMID- 2271935 TI - Electrophysiological properties of frog spinal dorsal horn neurons and their responses to serotonin: an intracellular study in the isolated hemisected spinal cord. AB - Frog dorsal horn neurons and their responses to serotonin (5-HT) were studied in intracellular recordings from isolated hemisected spinal cords. Electrophysiological properties were comparable to those of mammals. Bath application of 5-HT (10-50 microM) increased the excitability and caused membrane depolarizations in 7/14 cells, reduced or abolished activity and caused hyperpolarizations in 4 neurons, exerted a biphasic effect in two cells, and produced no detectable change in one neuron. The multiple effects of 5-HT may be mediated through different 5-HT receptor subtypes. PMID- 2271936 TI - Whole-cell voltage-clamp study of sodium current in neuroblastoma cells: effects of inhibition of neurite outgrowth by colchicine. AB - A method is described for the production of large numbers of neurite-free neuroblastoma cells that are especially suitable for studies involving whole-cell voltage clamp. Differentiation in the presence of colchicine yielded cells having abundant sodium channels, highly reproducible peak currents and no space-clamp problems. Treatment with this drug did not alter the electrophysiological properties of the cells. Colchicine might be similarly advantageous in voltage clamp studies of different ion channels and other types of cultured neurons. PMID- 2271937 TI - Sensory neglect in a frog: evidence for early evolution of attentional processes in vertebrates. AB - Mammalian-like 'sensory neglect' phenomena were elicited in Xenopus laevis by unilateral telencephalic lesion: after damage of the caudal striatum response rate to contralateral water waves was significantly lower than to ipsilateral ones. Response accuracy, however, was not affected. Within 6-8 weeks, animals recovered from neglect of unilateral stimuli; but simultaneous bilateral stimulation revealed an enduring neglect of contralateral stimuli. Latencies during acute neglect were significantly higher than after recovery. These results suggest that the neural mechanisms of selective attention might have evolved earlier than thought so far. PMID- 2271939 TI - Delayed wallerian degeneration in sciatic nerves of C57BL/Ola mice is associated with impaired regeneration of sensory axons. AB - Wallerian degeneration is delayed following sciatic nerve crush in C57BL/Ola mice. Compared to C57BL/6J mice, regeneration of sensory axons is significantly slowed in the Ola mice, but reinnervation does eventually occur. We conclude that Wallerian degeneration is a prerequisite for normal sensory axon regeneration following a crush injury to peripheral nerve. PMID- 2271938 TI - Differential cellular localization of enzymes of L-arginine metabolism in the rat brain. AB - Polyclonal rabbit antisera specific to argininosuccinate synthetase (ASS), argininosuccinate lyase and arginase revealed that these enzymes of L-arginine metabolism are generally localized in different cells of the rat brain. In the main olfactory bulb and the cerebellar cortex the three immunoreactivities were localized in different cells: in the somatic motor nuclei ASS-like immunoreactivity was localized in incoming fibers, and the other two enzymes were found in the motor neurons. The results suggest that L-argininosuccinate and/or L arginine may be transcellularly transported in the nervous system. PMID- 2271940 TI - Effects of intraventricular substantia nigra allografts as a function of donor age. AB - Transplantation of fetal substantia nigra into the brain can alleviate some of the manifestations of animal models of Parkinson's disease. The purpose of the present experiment was to determine the optimal embryonic donor age for solid tissue substantia nigra grafts. Rats with unilateral substantia nigra lesions were tested for rotational behavior in response to apomorphine. Animals then received intraventricular grafts of ventral mesencephalon from fetal donors of 11, 13, 15, 17, or 19 days gestational age, and were tested for rotational behavior 6 and 12 weeks after transplantation. After 12 weeks, animals receiving grafts from donors of 11 through 17 days gestation showed similar decreases (means = 42-58%) in rotation. All 4 groups showed greater decreases in rotation than the 19 day group (17%). In both the 11 and 13 day groups, however, there were substantial decreases in rotational behavior from the 6th to the 12th week testing periods. This study confirms that during a critical period of rat fetal development, between 17 and 19 days gestational age, the substantia nigra loses much of its ability to produce functional effects after transplantation. Grafts from very immature donors did not, however, produce markedly greater effects, and the youngest grafts required more time for the development of maximal effects. PMID- 2271941 TI - Differential expression of class I and class II major histocompatibility complex antigen in early postnatal rats. AB - Cells expressing major histocompatibility complex (MHC) antigens are rarely found in normal mature brains, but cells resembling microglia can be induced to express these antigens following the onset of neural degeneration. In young rats, these cells show spontaneous expression of class I MHC antigens, which is further enhanced in the superior colliculus by the degeneration resulting from eye removal. By contrast, class II MHC antigen expression does not occur spontaneously and can only be induced by eye removal when the lesion is performed after the first postnatal week, when the optic tract begins to myelinate. We suggest that different signals are responsible for induction of class I and of class II MHC antigen expression. PMID- 2271942 TI - The distribution and morphology of corticogeniculate axons in ferrets. AB - This study examined the distribution of axons in the lateral geniculate (LGN) and adjacent nuclei following injections of wheat germ agglutinin bound to horseradish peroxidase (WGA-HRP), [3H]proline and Biocytin into area 17 in ferrets. Terminal label was found in the LGN, perigeniculate (PGN), medial interlaminar (MIN) and lateral posterior (LP) nuclei. LGN label was more concentrated in the interlaminar zones. Analysis of axonal morphology showed that different axon types project to LGN, MIN and LP. These findings suggest that feedback pathways from area 17 are complex and composed of several classes of axons. PMID- 2271943 TI - The distribution of GABA in lumbar motoneuronal cell groups. A quantitative ultrastructural study in rat. AB - gamma-Aminobutyric acid (GABA)-containing profiles were identified at the ultrastructural level in rat lumbar motoneuronal cell groups by means of the postembedding immunogold technique, which is assumed to give very accurate quantitative results. It was found that 84.5% of the GABA-labeled terminals were of the F-type (containing many flattened vesicles), whereas P-type terminals (presynaptic to other terminals) constituted 9.2% of the GABAergic terminal profiles. A few of the GABA-labeled terminal profiles (1.7%) were G-type (containing many granular vesicles and presumed serotonergic), possibly indicating co-existence of GABA and serotonin. It is concluded that in spinal motoneuronal cell groups the large majority of the GABAergic terminal profiles were involved in postsynaptic inhibition of motoneurons, while only a minority was engaged in presynaptic inhibition. PMID- 2271944 TI - NMDA depolarizations and long-term potentiation are reduced in the aged rat neocortex. AB - N-Methyl-D-aspartate (NMDA) responses were recorded intracellularly in layer V neocortical neurons in in vitro slices taken from young (4-6 months) and aged (27 29 months) Fischer 344 rats. Increasing amounts of NMDA produced membrane depolarizations in both groups of cells. The regression analysis showed significantly reduced sensitivity to NMDA in old neurons compared to young. A significant long-term potentiation of the field potential evoked by subcortical white matter stimulation was present in young but not in old slices. These results suggest that aging results in a decreased sensitivity to NMDA and impaired synaptic plasticity in the neocortex. PMID- 2271945 TI - Capsaicin inhibits responses of fine afferents from the knee joint of the cat to mechanical and chemical stimuli. AB - In adult anaesthetized cats we studied the effects of capsaicin on the responses of single slowly conducting afferents of the knee joint to mechanical and chemical stimuli (bradykinin). An intra-arterial bolus injection of capsaicin into the joint reduced or abolished the responses to passive movements of the joint in 8 of 19 afferents and the responses to intra-arterially administered bradykinin in 10 of 11 units. Capsaicin was usually effective at 10(-4) to 10(-3) M. The inhibition was predominantly observed in nociceptive afferents, whereas most low threshold units were not desensitized. PMID- 2271946 TI - Serotonin reinnervation of the rat organum vasculosum laminae terminalis (OVLT) after 5,7-dihydroxytryptamine deafferentation. AB - The time course and pattern of serotonin (5-HT) reinnervation in the rat organum vasculosum laminae terminalis (OVLT) following intracerebroventricular administration of 5,7-dihydroxytryptamine were examined by means of [3H]5-HT uptake radioautography. 5-HT axonal varicosities reappeared in the OVLT within 3 months post-lesion. Six months later, they were found to have preferentially reinvested the neurohemal contact area (juxtavascular zone) of the organ. Regenerated terminals further increased in number. At the end of a 16-month survival time, they displayed normal-looking distributional patterns, similar to those of age-matched control animals, and formed new synaptic junctions in the juxtaventricular zone. The cellular mechanisms possibly responsible for 5-HT recovery in the OVLT are discussed. PMID- 2271947 TI - Decrease in [3H]hemicholinium binding to high-affinity choline uptake sites in deafferented striatum: restoration by oxiracetam. AB - Frontal cortical deafferentation of the rat striatum reduces the tone of striatal cholinergic neurons. We used biochemical and autoradiographic techniques to investigate whether the [3H]hemicholinium-3 ([3H]HCh-3) binding to sodium dependent high-affinity choline uptake sites was influenced by this lesion. Frontal deafferentation produced a reduction of about 30% in the number of [3H]HCh-3 binding sites (Bmax) in striatum, with no significant changes in the binding affinity (Kd). Autoradiography showed a significant reduction of [3H]HCh 3 binding sites in the anteromedial portion of the striatum, but not in the posterior part of frontal deafferented rats. Oxiracetam (100 mg/kg), a nootropic drug, did not affect the distribution of [3H]HCh-3 binding sites in sham-operated rats but completely overcame the reduction in the number of [3H]HCh-3 binding sites in deafferented striatum. PMID- 2271948 TI - Effects of repetitive conditioning crush lesions on regeneration of the rat sciatic nerve. AB - The effect of repetitive conditioning lesions was tested on regeneration of the rat sciatic nerve. The nerve was conditioned by crush lesions one, two or three times with an interval of 2 or 4 days between each successive lesion. Axonal elongation was measured 3 days after a final test crush lesion. Two conditioning lesions stimulated axonal elongation more than one, while a third conditioning lesion had no further effect on axonal outgrowth. However, if the number of conditioning lesions were varied within a constant conditioning interval, outgrowth after the test lesion was the same. This suggests that the conditioning interval and not the number of conditioning lesions determined the outgrowth after a test lesion. When the conditioning lesion(s) and the test lesion were made at the same place, outgrowth was longer than if the lesions were spatially separated. Incorporation of [3H]thymidine in the regenerated nerve segment showed that proliferation of non-neuronal cells was initiated by each lesion. By counting the number of cell nuclei this proliferation was shown to correspond to an increase of cells in the regenerating nerve. It is therefore possible that the greater number of non-neuronal cells in the distal nerve segment accounts for the enhanced conditioning lesion effect in nerves where the conditioning and test lesions are made at the same place. PMID- 2271949 TI - Distribution of GABA-like immunoreactivity in guinea pig vestibular cristae ampullaris. AB - Post-embedding immunocytochemical techniques were used to assess distribution of gamma-aminobutyric acid (GABA) in the guinea pig cristae ampullaris. GABA-like immunoreactivity (GABA-LIR) was found in the cytoplasm of both type I (HCI) and type II hair cells (HCII), in the afferent calyx (AC) contacting HCI and some myelinated fibers in the subjacent stroma. HCI and its calyceal contacts showed variation in GABA-LIR, suggesting different populations in HCI and AC. These results support a putative afferent neurotransmitter role of GABA in HC and a possible degradation site of GABA in AC. PMID- 2271950 TI - Vasopressinergic neurons in the magnocellular nuclei of the human basal forebrain. AB - Vasopressinergic structures were examined within the magnocellular nuclei of the human basal forebrain. Vasopressinergic neurons were found in all parts of the diagonal band nucleus, and less frequently in the anteromedial subnucleus of the basal nucleus (Meynert). They belong to the group of large multipolar neurons, previously defined as type I neurons, characterized by fine lipofuscin granules widely spread within the soma. Species differences exist in the topographic arrangement of vasopressinergic structures. PMID- 2271951 TI - Sex, handedness, and the morphometry of cerebral asymmetries on magnetic resonance imaging. AB - Cerebral morphometry of linear measurements and hemispheric, frontal, temporal and parietal areas on MRI of 104 normal adults was analyzed for sex and handedness and right-left differences. The right hemisphere was significantly larger across all groups, but the left frontal width and area was larger in left handers. MANOVA showed separate effects of hand and sex for linear measures; right-handers had larger right anterior frontal, and left parietal and occipital widths. Ratios of L - R/L + R eliminated sex differences related to overall brain size, however, a significant sex-by-hand interaction was shown by the parietal area ratios, indicating larger left side in right-handed males and left-handed females. A 3-dimensional 'torque' was postulated, where the upper and rostral portions of the hemispheres were larger on the right and the lower and caudal parts equal, or slightly larger on the left. The relationship of anatomical asymmetries, sex and handedness is multi-dimensional, and may explain some of the variability of normal cognitive functions and deficits after brain damage. PMID- 2271952 TI - The increases in rat cortical and midbrain tryptophan hydroxylase activity in response to acute or repeated sound stress are blocked by bilateral lesions to the central nucleus of the amygdala. AB - Sound stress (SS) (120-dB pulses of 100 ms duration, every min for 1 h) produces an elevation of in vitro cortical or midbrain tryptophan hydroxylase activity from male Sprague-Dawley rats that is abolished, in vitro, by incubation of the enzyme preparation with alkaline phosphatase. SS, when repeated on 3 different occasions, the first 2 sessions 24 h apart and the 2nd and 3rd session separated by 48 h, produces a stable increase in the in vitro enzyme activity that is unaffected by alkaline phosphatase. Bilateral lesions to the central nucleus of the amygdala block both increases in enzyme activity obtained in response to acute and repeated SS, but leave enzyme activity from sham-stressed rats unaffected. PMID- 2271953 TI - The adenosine analog, 5'-N-ethylcarboxamidoadenosine, exerts mixed agonist action on cardiorespiratory parameters in the intact but not decerebrate rat following microinjections into the nucleus tractus solitarius. AB - A limited occipital craniotomy was conducted on intact and decerebrate urethane anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), a metabolically stable adenosine analog which exhibits mixed agonist properties for adenosine receptor subtypes, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 30-min test period. In the intact rat, microinjections of NECA produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. On the other hand, microinjections of NECA into this region of the NTS of the intact rat elicited complex, bi-directional cardiovascular responses, producing hypotension (at lower doses) and pressor responses (at higher doses) in addition to bradycardia (at lower doses). In an effort to examine the functional interactions between the NTS and forebrain structures involved in cardiorespiratory control, microinjections of NECA in the identical dose range were made into the same NTS sites of a separate group of urethane anesthetized, spontaneously breathing rats in which reciprocal connections between forebrain areas and the brainstem had been disrupted by acute supracollicular decerebration. A simulating electrode, placed in the paraventricular nucleus of the hypothalamus (PVH), was used to confirm complete transection during the experiment and to ascertain the integrity of reciprocal connections between the brainstem and rostral brain regions involved in cardiorespiratory control. Although decerebration at the supracollicular level negligibly affected basal cardiorespiratory parameters, microinjections of NECA into the NTS revealed dramatic differences in the cardiovascular response patterns between intact and decerebrate rats. Whereas cardiovascular responses elicited by microinjections into the NTS were significantly affected by supracollicular decerebration, respiratory responses were highly similar for both intact and decerebrate animals. Indeed, repeated measures MANOVA indicated that there were no significant differences in the time-related or dose-related responses in the depression of respiration between decerebrate and intact rats following NECA microinjections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271954 TI - Corticofugal influence on taste responses in the parabrachial pons of the rat. AB - Although the anatomy of centrifugal input to gustatory neural structures has been described, little is known of the physiological mechanisms that convey this influence or of their functional significance. As a first step in the investigation of these issues, the effect of a reversible lesion in the gustatory neocortex (GN) on the neural code for taste in the parabrachial nucleus of the pons (PbN) was studied in rats. Electrophysiological responses to taste stimuli bathed over the tongue were recorded from single units in the PbN before, after and following recovery from an infusion of procaine-HCl into the GN. Test stimuli consisted of sapid solutions of NaCl (0.1 M), HCl (0.01 M), sucrose (0.5 M), Na saccharin (0.004 M) and quinine-HCl (0.01 M). Infusions of procaine into the GN were correlated with both specific and nonspecific effects on the responsivity to gustatory stimuli in the PbN. Specific effects included: (1) changes in the magnitude of response to some tastants, but not others, in a given PbN unit, (2) changes in the across unit patterns produced by sweet stimuli and (3) the appearance of OFF responses in a subset of PbN units. Nonspecific effects were evidenced by changes in the spontaneous rates of activity and by enhancement or suppression of responses across all the tastants tested in a subset of PbN units. Comparison of these results with reports on the effects of decerebration suggests that some of these effects may be accounted for by interruption of the descending input from the GN to the PbN. In addition, the stimulus-specific effects that were noted following procaine infusion into the GN provide support for the suggestion that the GN specifically modifies the electrophysiological patterns that are evoked by salient taste stimuli. PMID- 2271955 TI - Development of hippocampal long-term potentiation is reduced by recently introduced calpain inhibitors. AB - The effects of two recently synthesized inhibitors of calpains, calpain inhibitor I (CiI) and calpain inhibitor II (CiII) were tested on the development of long term potentiation (LTP) in region CA1 of rat hippocampus. Slices maintained in 100 microM of CiI or CiII showed an initial degree of potentiation after theta burst stimulation that, in contrast to controls, slowly decayed across time. The effects of CiI and CiII appeared to be independent of possible actions on the physiological mechanisms that take place during the induction stage of LTP. Since these inhibitors are more potent and specific than leupeptin in blocking calpain activity, their effects on LTP can be more convincingly ascribed to a selective blockade of the calcium-sensitive protease. Accordingly, the results favor the idea that a proteolytic event of the kind found after N-methyl-D-aspartate receptor activation is an intermediary step in the development of LTP. PMID- 2271956 TI - Reorganization of GABAergic synapses in the viper optic tectum following retinal deafferentation. AB - The immunocytochemical analysis of the viper optic tectum was carried out with an anti-gamma-aminobutyric acid (anti-GABA) antiserum following retinal deafferentation for survival times ranging from 10 to 90 days. The ultrastructure of the SGFS neuropil revealed that among the two types of axon terminals, namely pleiomorphic (P) and spherical (S) boutons, a subtype of the latter (S2), corresponding to the retinal terminals, was found to degenerate at varying rates. In most cases, this resulted in the glial engulfment of the presynaptic partner, leaving the postsynaptic differentiation free (FPSD). Beyond the two first months, the asymmetrical freed postsynaptic differentiations (FPSDs) were progressively and partly reafferented by GABA-positive P axon terminals through a sliding process. Three months postoperative, the number of GABA-positive P axon terminals which, in normal animals, establish asymmetrical contacts (1-2%), was found to increase to approximately 10%. The postsynaptic differentiation may represent a mismatched receptor area for the new competing presynaptic partners. The functional implications of such 'axonal terminal sprouting' are discussed. PMID- 2271957 TI - Coding of stimulus location and intensity in populations of mechanosensitive nerve fibers of the raccoon: I. Single fiber response properties. AB - The primary aim of this study was to determine and compare the receptive field (RF) characteristics and response properties of single mechanosensitive nerve fibers innervating the glabrous skin of the forepaw and hindpaw of the raccoon. The action potentials of 129 median nerve fibers and 61 posterior tibial nerve fibers were recorded in response to punctate mechanical stimuli varying in location and intensity. The stimuli were delivered to six standard test sites on digit 1 and the contiguous pads of each paw. Attempts were made to classify each fiber according to its rate of adaptation to sustained stimulation; the RF of each fiber was mapped using a standard series of stimulus intensities. The results indicated that the response properties of individual fibers were highly complex and depended on the location and intensity of stimulation. 1) The distributions of absolute threshold were not different for the median or tibial nerve fibers or for different classes of fibers based on adaptation rate. A distal to proximal increase in threshold was found for each paw, suggesting a corresponding gradient of sensitivity across the glabrous skin. 2) Threshold RF areas did not vary across either paw nor did they differ between the two paws. Suprathreshold RFs were quite large relative to expected tactile acuity and displayed complex features. 3) Response properties such as adaptation rate, on- and off-responses, were found to vary with both stimulus location and intensity. It was concluded that the responses of individual nerve fibers could not uniquely encode any stimulus parameter tested, and that the properties of single fibers could not account for apparent differences in tactile acuity across each paw or between the two paws. PMID- 2271958 TI - Coding of stimulus location and intensity in populations of mechanosensitive nerve fibers of the raccoon: II. Across-fiber response patterns. AB - The major aim of this study was to determine whether information about stimulus location and intensity can be precisely encoded in the population response profiles of mechanosensitive nerve fibers. Across-fiber patterns (AFPs) were reconstructed using data obtained previously (58) from 129 single median nerve fibers and 61 posterior tibial nerve fibers of the raccoon. Punctate mechanical stimuli of varying intensities were presented to six standard test sites on the glabrous skin of the forepaw and hindpaw, and the AFP produced by each unique stimulus was determined. Innervation density (ID) at each of the test sites was estimated from the integrated voltage of compound action potentials evoked by constant current stimulation of the skin at each site. Differences in ID between corresponding regions of the forepaw and hindpaw were estimated by counts of myelinated fibers and measurements of skin areas supplied by the median and tibial nerves, respectively. All AFPs were adjusted to take into account the differences in ID among the various skin sites on the two paws. The data indicated that different stimulus locations and intensities on each paw could be precisely and unambiguously encoded by AFPs; location was represented primarily by the shape of the AFP, whereas intensity was represented by the height of the AFP. The discriminability of location and intensity was shown to be directly related to the magnitude of the difference between the AFPs elicited by any two stimuli. Consistent with expectations, AFPs for stimuli delivered distally on each paw showed greater differences as a function of stimulus location and intensity than AFPs for stimuli applied proximally. Furthermore, AFPs produced by stimuli to the forepaw showed greater changes than AFPs for stimuli to comparable sites on the hindpaw. It was concluded that systematic differences in the population response profiles of median and tibial nerve fibers could account for regional variations in tactile acuity across each paw and differences between the two paws. PMID- 2271959 TI - Collateral input to the paraventricular and supraoptic nuclei in rat. II. Afferents from the ventral lateral medulla and nucleus tractus solitarius. AB - In the rat, medullary afferents to the hypothalamic magnocellular nuclei mediate the baroreceptor reflexes of vasopressinergic neurons and the cholecystokinin- or gastric distention-induced excitation of oxytocinergic neurons. One strategy that reflexes such as these may use to coordinate the activity of magnocellular neuroendocrine neurons is collateral branching of input. Previous work has shown that the distributions of medullary neurons projecting to the paraventricular and the supraoptic nuclei overlap and that their axons branch. Thus, we hypothesized that single neurons in the ventral lateral medulla and/or the nucleus tractus solitarius would project to both the paraventricular and supraoptic nuclei via collateral branches of their axons. Medullary afferent neurons were retrogradely labeled after injection into the paraventricular and the supraoptic nucleus on one side of the brain with two different fluorescent tracers: Fluoro-Gold or rhodamine-labeled latex microspheres. The topographic distribution of labeled cells in the medulla containing either a single fluorescent tracer or both tracers were plotted. Of these labeled neurons, a small percentage (7%) contained both dyes, suggesting that they send collateral branches to both of the magnocellular neuroendocrine nuclei injected. Single labeled cells were both ipsi and contralateral to the injected side (53% ipsilateral), but most double labeled cells were ipsilateral (84%). In rats, areas that project to both the paraventricular and the supraoptic nuclei may act upon both nuclei together. Thus, afferent inputs, in conjunction with the known inter- and intracellular changes that take place within the magnocellular nuclei, may be involved with the coordinated responses throughout magnocellular neuroendocrine system during medullary reflexes, i.e., the baroreceptor-mediated reflexes or the gastric distention reflexes. PMID- 2271960 TI - Differential effects of fasciculus retroflexus lesions on serotonin, glutamate and gamma-aminobutyrate content and choline acetyltransferase activity in the interpeduncular nucleus. AB - After placing bilateral electrolytic lesions in the fasciculus retroflexus (FR) of the rat, the endogenous content of serotonin, glutamate and gamma aminobutyrate (GABA) as well as choline acetyltransferase activity (ChAT) were measured in the interpeduncular nucleus (IPN) at the 7th, 28th and 120th survival days. Confirming earlier results, an almost total depletion of ChAT was obtained in the IPN following complete FR lesions at any survival day studied. In such cases, the following changes were observed; 1) the serotonin level increased consistently and roughly doubled at the 120th survival day, suggesting heterotypic sprouting of serotonergic fibers and/or enhanced serotonin synthesis in the serotonergic neurons in the IPN, 2) the glutamate level decreased by approximately one-half, while the activity of high affinity uptake of glutamate remained unaltered, at the 7th survival day, suggesting a lowered glutamate formation coupled with lowered glucose utilization in the IPN, and 3) the GABA level decreased at a slower rate and reached one-third of the control at the 120th survival day, for which either transsynaptic degeneration of GABA neurons in the IPN or a suppressed metabolic rate in the GABA shunt following the lowered glutamate formation is a possible explanation. PMID- 2271961 TI - African green monkeys have sexually dimorphic and estrogen-sensitive hypothalamic neuronal membranes. AB - Previous studies have shown sex differences in intramembrane particle content in the arcuate neurons of the rat hypothalamus. In this study, freeze-fracture replicas were prepared from the infundibular hypothalamus of adult African green monkeys (Cercopithecus aethiops) in order to determine whether primates also have sexual dimorphism in neuronal membranes. Intramembrane particles (IMP) were quantitatively assessed in the perikaryal plasma membranes of infundibular neurons. Four groups of monkeys were studied: intact males, intact females, ovariectomized females injected with 20 mg of estradiol valerate over 10 days and ovariectomized females injected with vehicle (castor oil). Membranes from females showed an increased numerical density of IMPs when compared to males. Ovariectomy of females did not affect IMP content, while estrogen administration resulted in a significant decrease in IMP numerical density to reach male values. These findings indicate a sex difference in neuronal membranes in the hypothalamus of monkeys and suggest that as in rodents, neuronal plasma membrane organization in higher primates may be modulated by gonadal steroids. PMID- 2271962 TI - Inhibition of spinal reflexes by paramedian reticular nucleus. AB - The inhibitory actions of the paramedian reticular nucleus (PRN), and its neighbouring structures, i.e., midline raphe nuclei (MRN) and dorsal medullary depressor area (DMD) on the knee jerk (KnJ) and crossed extension movement (CEM) induced by central sciatic stimulation and on the L5 ventral root response (EVRR) evoked by central tibial stimulation, were studied in cats under urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia alone, IP or further paralyzed with atracurium besylate (0.5 mg/kg/30 min), IV. Electrical stimulation of the above areas with rectangular pulses (80 Hz, 1.0 msec, 100-200 microA) decreased systemic arterial blood pressure (SAP) in an average value of: 36 +/- 3 mmHg for PRN; 19 +/- 2 mmHg for MRN; and 23 +/- 3 mmHg for DMD. The KnJ and CEM were almost completely suppressed by simultaneous PRN stimulation. The EVRR, including mono- and polysynaptic spinal reflexes with transmission velocity from 10 to 60 m/sec or above, were also suppressed. MRN stimulation only inhibited the KnJ, CEM and polysynaptic spinal reflexes with transmission velocities between 25 and 60 m/sec, but facilitated spinal reflexes with conduction velocities below 10 m/sec. On the other hand, DMD stimulation resulted in small suppression of KnJ, CEM and inhibition of polysynaptic spinal reflexes with conduction velocities between 25 and 60 m/sec. Even though MRN and DMD partially inhibited polysynaptic spinal reflexes, the magnitude of such inhibition was much smaller than that produced by PRN (-20% and -22% vs. -48%). The above-mentioned PRN effects on SAP and EVRR persisted in chronic animals decerebellated 9-12 days before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271963 TI - Corticotropin-releasing factor antagonist blocks microwave-induced decreases in high-affinity choline uptake in the rat brain. AB - Acute (45-min) irradiation with pulsed low-level microwaves (2450-MHz, 2 microseconds pulses at 500 pps, average power density of 1 mW/cm2, whole-body average specific absorption rate of 0.6 W/kg) decreased sodium-dependent high affinity choline uptake (HACU) activity in the frontal cortex and hippocampus of the rat. These effects were blocked by pretreating the animals before exposure with intracerebroventricular injection of the specific corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical-CRF9-41 (25 micrograms). Similar injection of the antagonist had no significant effect on HACU in the brain of the sham-exposed rats. These data suggest that low-level microwave irradiation activates CRF in the brain, which in turn causes the changes in central HACU. PMID- 2271964 TI - Anterior decerebration blocks visual habituation in the larval salamander (Ambystoma punctatum). AB - Amputation of the rostral half of the cerebrum induces a compulsion-like reaction in larval Ambystoma punctatum towards Enchytraeus protected within glass vials. Normal and craniotomized larvae are visually attracted to worm-containing vials, as revealed by time-lapse video taping but, after several unsuccessful attempts to get the prey, habituate and depart. The video tapes revealed that anteriorly decerebrated animals spent as much as 100 of 120 minutes at the worm-containing vial, repeatedly but futilely attacking the glass. The data indicate that the telencephalon plays an active negative role in the salamander larva's visually guided behavior. PMID- 2271965 TI - Stressor-induced behavioral alterations in intracranial self-stimulation from the ventral tegmental area: evidence for regional variations. AB - Exposure to uncontrollable footshock reduced responding for electrical brain stimulation (ICSS) from the ventral tegmental area (VTA) of the CD-1 mouse. Such an effect, however, varied with electrode position in the tegmental field. In both a rate-dependent and a current intensity paradigm, ICSS from the dorsal VTA was reduced immediately, 24 hr and 168 hr following exposure to acute uncontrollable footshock. In contrast, ICSS from the ventral VTA was unaffected by the stressor regimen. These data are consistent with the suggestion that a stressor may reduce the rewarding value ordinarily derived from ICSS. Inasmuch as the stressor differentially affected ICSS from the dorsal and ventral tegmentum, these data provide evidence for a functional differentiation within the midbrain tegmental area. PMID- 2271966 TI - Intracerebroventricular injection of kynurenic acid, but not kynurenine, induces ataxia and stereotyped behavior in rats. AB - In the present studies the behavioral-pharmacological effects of kynurenine and its metabolite kynurenic acid were investigated after intracerebroventricular (ICV) microinjection in rats. Kynurenine (0.1 and 0.2 mumol ICV) produced slight behavioral changes, but its metabolite kynurenic acid (0.2 mumol ICV) induced marked ataxia, stereotyped behavior and muscular hypotonia in a dose-dependent manner. The kynurenic acid-induced neurological symptoms were partially inhibited but not eliminated by ICV pretreatment with D-serine (0.5, 2.5, 5 mumol), which is a selective agonist at the strychnine-insensitive glycine binding site of the NMDA-receptor complex. Our results support the following conclusions: 1) kynurenine (0.1 or 0.2 mumol, ICV) results in slight stereotypy and ataxia, but the speed of its metabolism to kynurenic acid in this paradigm is not sufficient to produce concentrations of kynurenic acid, which are able to elicit marked ataxia and stereotypy; 2) the duration of kynurenic acid-induced behavioral abnormalities is correlated with the length of disappearance of micro-injected kynurenic acid from brain tissue; 3) D-serine which is an agonist at the glycine site linked to the NMDA complex, partially antagonizes but does not eliminate the neurological disturbances induced by ICV kynurenic acid injection. PMID- 2271967 TI - Glutathione levels in specific brain regions of genetically epileptic (tg/tg) mice. AB - The tottering (tg/tg) mouse is a genetic model of human generalized epilepsy; these mice exhibit spontaneous absence seizures accompanied by bilaterally synchronous spike-wave discharges (6). The mechanism(s) for seizure activity are unknown in these mice. Several recent studies have suggested that membrane lipid peroxidation may be causally involved in some forms of experimentally induced epilepsies (18). Since reduced glutathione (GSH) is the most important free radical scavenging compound in vivo that can prevent membrane lipid peroxidation, the objective of this study was to investigate GSH concentrations in specific central nervous system regions of genetically epileptic, tg/tg, mice as compared to age-matched controls. Three brain regions, cerebellum, hippocampus, and occipital cortex, were dissected, weighed and the concentrations of reduced and oxidized glutathione (GSH and GSSG, respectively) were measured in each of these tissues. GSH content was significantly lower in the occipital cortex of tg/tg mice compared to controls; no differences were observed in the other two brain regions examined. Total GSH content (GSH plus 2 x GSSG) paralleled GSH concentration differences. GSSG content from tg/tg mice was lower in the hippocampus and occipital cortex, compared to controls. This is the first report of an association between decreased central nervous system glutathione concentrations and seizure activity in animals exhibiting generalized seizures. PMID- 2271968 TI - [History of echocardiography in Czechoslovakia]. PMID- 2271969 TI - [The present state of echocardiography in Czechoslovakia]. AB - The level of present-day echocardiography in the CSFR is comparable to that found in other countries. Similarly as abroad, over here too, echocardiography has become the most useful and the most widely spread noninvasive method, which gradually keeps narrowing down the indication range for catheterization of the heart and vessels. One- and two-dimensional imaging is being used routinely in all relevant departments. Contrast and exercise echocardiography are frequently used. Doppler echocardiographic techniques are gradually introduced into current practice. Experience keeps accumulating on the application of transesophageal echocardiography, including its use in circulatory emergencies and cardiosurgical procedures. Adequate economic, conceptual and educational conditions will have to be established to promote further development of echocardiography in the CSFR. PMID- 2271970 TI - [Diagnosis of congenital heart defects in childhood]. AB - Echocardiographic diagnosis of inborn developmental defects of the heart in children differs from the approach used in adults. Examination from the subcostal and suprasternal space is of utmost importance. On using "deductive echocardiography" individual segments of the heart are gradually assessed in the two-dimensional echocardiographic picture. On evaluating pathological changes (particularly borderline values), the use of Doppler signal and one-dimensional imaging is equally important in children as it is in adults. PMID- 2271971 TI - [Alternative approaches in stress echocardiography]. AB - The authors' own experience as well as literary information on stress echocardiography in diagnosis of ischemic heart disease is presented. Besides dynamic postexercise echocardiography, which they consider to be the most adequate form of stress echocardiography, the authors analyze the possibilities of so-called alternative approaches, i.e. dipyridamole echocardiographic test and the use of transesophageal atrial pacing. The results of the three echocardiographic stress modalities show that their overall informative value is comparable. The practical performance is most favorable in the pharmacologic test, the highest safety is warranted in transesophageal atrial pacing, and tolerance proved to be best in the dynamic postexercise test. On choosing the actual stress modality, the authors recommend to weigh the advantages against the drawbacks before deciding on the approach of choice in the given situation so as to obtain optimal results. PMID- 2271972 TI - [Echocardiographic aspects of developmental changes in ventricular function during acute myocardial infarct]. AB - The development of ventricular function in the course of the first three weeks after acute myocardial infarction (AMI) was studied in the light of repeated examinations of 76 patients. Segmental derangement of mobility keeps increasing over the first postinfarction days in many patients, while the second and third week show a trend towards improvement. The derangements of segmental kinetics can be evaluated quantitatively by means of a computer or semi-quantitatively by subjective assessment. The former approach is suitable particularly in research work, the latter is fully satisfactory for routine practice. Concavity of the left ventricular wall was detected in 34.8% of the patients and in 56.5% of these the concavity appeared already on the first post AMI day. The organism responds in several ways to derangements of segmental mobility. First the sympathoadrenal activity is increased, which is echocardiographically reflected by hyperkinesia of the unaffected areas of the left ventricle. Further on segmental pliability decreases and the left ventricle becomes dilated by heterometric regulation. Reduced right ventricular function was recorded in 48.4% of patients with infarction of the lower wall and in 11.4% of patients with infarction of the anterior wall. PMID- 2271973 TI - [Segmental analysis of left ventricular wall mobility]. AB - The authors present their experience with subjective and quantitative evaluation of the mobility of the left ventricular wall of the heart. The combination of computer technique and two-dimensional echocardiography makes it possible to evaluate quantitatively the function of the left ventricule of the heart by the method of segmental analysis of wall mobility. Segmental analysis has proved to be a suitable method for assessing the function of the left ventricle particularly in subjects with threshold or slightly decreased functional values. The authors use the method in studying the functional response of the left ventricle to diagnostic or therapeutic intervention. The method yields important information also on the development of left ventricular function after myocardial infarction in follow-up studies. Subjective assessment is a less demanding approach and when carried out expertly, the extent of muscular damage can satisfactorily be evaluated. PMID- 2271974 TI - [Stress echocardiography in clinical cardiology]. AB - In their generally designed presentation the authors focus on practical problems concerning indication, different stress modalities and projections, evaluation and interpretation of findings, as well as on technical novelties and their use. Only dynamic exercise echocardiography is being discussed. Currently available knowledge is assessed in the light of the authors' own experience. Problems of evaluation and interpretation are considered to be most intricate. In the authors' opinion, many technical problems which have prevented the routine use of the method in practice will be eliminated by introducing technical novelties such as digitalization of the display with image loop. Other innovations will certainly be used to advantage and render the method less demanding and far more widespread. PMID- 2271975 TI - [Echocardiographic diagnosis of myxoma in the left side of the heart]. AB - Echocardiographically established tumors occurring in the left side of the heart in three female patients are described. Two patients had myxoma in the left atrium and one patient presented with a rarely occurring pseudomyxoma in the left ventricle. Two patients were operated on and the echocardiographic finding was verified topically and histologically. One of the patients with myxoma in the left atrium has so far refused cardiosurgical treatment. PMID- 2271976 TI - [Determination and assessment of biological age in 40-85-year-old persons]. AB - Biological age was determined separately for men and for women in a series of 120 subjects (66 women) aged 40-85 years (mean age 66 +/- 11.6 years). The established biological age correlated significantly with the chronological age of the subjects investigated. For the calculation of functional age a battery of 10 tests covering 7 functional systems was developed to meet the requirements of the geriatrician and one of 6 tests covering 5 functional systems for the conditions of the general practitioner. The tests are undemanding as to time and procedure and reflect age and sex differences in the population of 40-85 year old people. A new method for the evaluation of biological age was suggested and used, namely the method of interval assessment and of correction of biological age with respect to the chronological age of the proband. PMID- 2271977 TI - [Bulletin of the National Academy of Medicine. Volume 173--Index 1989. 9th supplement]. PMID- 2271978 TI - [The eulogy of Maurice Pestel (1914-1989)]. PMID- 2271979 TI - [Development of the concept of antidotes: the contribution of clinical toxicology]. AB - The clinical study of antidotes has been limited until the recent development of Clinical Toxicology Centers where rare but demonstrative observations were collected and a critical approach for the validation of therapy organized. After the period of setting of respiratory assistance in coma due to acute intoxication by psychotropic drugs, the knowledge of biochemical receptors for toxic molecules and the production of antagonistic molecules allows the setting of drugs with unquestionable efficacity according to the accumulation of data in CTC and to an international collaboration and consensus program. Some pharmacological research considered as necessary have permitted the discovery of new situations as frequent cyanhydric intoxications due to plastic furniture during home fires. The progress in antibodies-antidotes bioformation and pharmaceutical production is necessary to antagonize some acute and often lethal intoxications like these due to colchicine and paraquat. PMID- 2271980 TI - [Flavonoids: antithrombotic agents or nutrients?]. AB - Flavonoids are a vast group of natural substances, but their pharmacological properties have not all been explored. The term flavonoid is used at large to designate a series of more than 4,000 molecules, which in fact can have very heterogenous molecular structures. We have shown that some flavonoids are good inhibitors of cyclic nucleotide phosphodiesterase (PDE). The most active PDE inhibitors among the flavonoids were also good inhibitors of the aggregation of human platelets in vitro. This suggests that flavonoids could serve as a template for the development of new anti-platelet drugs. However, a direct extrapolation of our experimental results to possible therapeutical use of flavonoid-containing medicinal plant extracts is not possible. The metabolic fate of these plant flavonoids is poorly understood, and their absence of toxicity has not always been clearly demonstrated. Flavonoids are also present in a regular diet in significant amounts. The role of these dietary flavonoids in the prevention of thrombotic diseases or atherosclerosis should also be investigated. PMID- 2271981 TI - [The medical service of sickness insurance: its future]. AB - Since its creation, the Medical Service of Health Insurance has known an important evolution. Initially, its essential role was to control the allowances paid to the insured persons of the regimes of Health Insurance. Its aspect was rather coercive. But since 1960 a change has been outlined with the creation of the "Haut Comite Medical de la Securite Sociale": the Medical Control left its place to the Medical Service. With this denomination, its functions never stopped expanding. The Medical Service maintained its tasks of control devolved by the different regulations, and that is how it falls to it to express a view about long term diseases, disability occupational injuries, etc. It is also responsible for setting up "selective" controls with regard to some of medical or ancillary medical acts. But this taskwork is coupled with an important activity: the counsel. This responsibility is orientated in three directions: the Health Insurance Associations, the insured persons, and the Health Professions particularly as a part of the conventions binding them to the organizations of the French social protection system. During these last years new date intervened in health insurance matters in consequence of the economical crisis. Henceforward, it suits to find just a balance between a social protection of a high standard and adapted care of quality for the best cost. New opportunities are offered to the Medical Service to face this situation and gave it also a fresh impulse. This new evolution fits into an activity of public health considering the progress of the medicine. This activity must be orientated to a better knowledge of dispensed care and its good employment. Several orientations must be detained. In disease matters, informations in possession of the medical services are to be operated and, thanks to the data processing, a balance sheet of expenses will be drawn up, comparing them with diagnostic and therapeutic means. These studies, whose results will be published, must be guided with an exemplary scientific strictness and be supported by uncontested leading people in the medical world. Hospitalization is the other field where the role of the medical service must be essential. It certainly charges to continue the individual controls. But it must go further and be interested in the hospital working, as well as in the aggregate as by hospital service. This permits to get indispensable informations for useful decisions in view of a better hospitalisation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2271982 TI - [Bovine spongiform encephalopathy: a new entity caused by a non-conventional transmissible agent]. AB - In 1986, a new neurologic disease appeared in the Great Britain's Cattle. According to its histological lesions, this condition belongs to the group of transmissible encephalopathies known as spongiforme encephalopathies (SE). These SE are associated with no-conventional transmission agent (NCTA) or Prion. At the time of writing, over 13,000 cases of Bovine spongiforme encephalopathy (BSE) have occurred in UK. The most likely origin of this dramatic outbreak would be an oral contamination of Cattle by the feeding of sheep carcasses or of all infected with scrapie, another SE, incorporated to concentrates. Possible factors as changes (lower temperatures and reduced use of organic solvents to extract fats) in the rendering process could have preserved the very resistant Prion in these concentrates. The important lessons resulting from our present knowledge and hypothesis are there would be no species barrier to impede transmission of the NCTA through oral route. The question concerns the public health risks posed by BSE. Two related diseases of human are Kuru and Creutzfeldt-Jacob disease. At the present time, based upon epidemiological datas on scrapie, BSE is unlikely to be a major threat to humans. Nevertheless, precautionary steps to reduce a potential risk to an absolute minimum were taken by British regulations and more recently, by European directives. PMID- 2271983 TI - [Is there a role for parasites in the etiology of inflammatory rheumatism?]. AB - Parasitic rheumatism is a rare condition characterized by inflammatory joint manifestations due to a parasitic infestation without parasites into joint cavity, (but, with circulating immune complexes, in serum, and synovial fluid; and with immunoglobulins and complement deposits in synovium in some cases reported in the literature). The number of parasites (now 15) which can induce such an arthritis by immune mechanisms is steadily increasing. In all, but few cases of parasitic rheumatism, usual parasitic manifestations (diarrhea, abdominal pain, nausea...) are mild or absent; but, if present, they are a very good criteria to evoke the diagnosis. Clinical pictures of arthritis induced by parasitic infestation are very polymorphic, and non specific of the involved parasite; they seem to depend on genetic predisposition: the symptoms are monoarticular, pauciarticular, or polyarticular, involving small, medium, and or large joints. They can mimic the clinical picture of different inflammatory rheumatic diseases. The most striking feature of parasitic rheumatism is the failure of antirheumatic agents (especially non steroidal anti-inflammatory agents), contrasting with the dramatic efficacy of specific anti-parasitic treatment. The proof of the responsibility of parasitic infestation by indirect mechanism is given by an exceptional case report of a patient with arthritis, dramatically cured after removal of larvae from Anisakiasis gastric granuloma. To explain the uncommon occurrence of this variety of reactive arthritis, due to parasitic infestation, despite the high prevalence of parasitic infestation in the world, hypothesis of genetic predisposition seems valuable. Among 34 well documented reported cases of parasitic rheumatism in the literature, HLA B 27 antigen has been researched in 13; out of these 13, HLA B 27 is absent in 9; in 7 out of these 9, clinical picture is symmetrical polyarthritis. Out of the 13 cases, HLA B 27 is present in 4: In all these 4 cases, clinical picture is asymmetrical pauciarthritis, mimicking arthritis of Reiter's disease. PMID- 2271984 TI - [A eulogy of Paul Bregeat (1909-1989)]. PMID- 2271985 TI - [Chronicle of an announced death: the end of intrinsic asthma]. AB - The word "intrinsic" asthma which is not usually quoted by French authors should be eliminated from the medical vocabulary. Similar past history, clinical symptoms, house or occupational exposure are found in all varieties of asthma. Histological features are the same in atopic asthma and late onset asthma, apparently non allergic. On immunologic point of view there are two types of IgE receptors type I on mastocytes, type II on inflammatory cells, with immunomodulation by IL4 and T lymphocytes. On the other hand, atopic status is an autosomic dominant inherited trait, with a gene locus on the chromosome 11 Q and may be transferred with bone marrow cells graft. Finally asthma appears to be a local variety of IgE hyperresponsiveness to environmental factors. These basic notions have practical consequences and legal aspects. PMID- 2271986 TI - [AIDS dementia]. AB - Human immunodeficiency virus type I (HIV), the etiology of AIDS is also the cause of a primary infection of the central nervous system. The AIDS Dementia Complex is a common and important cause of morbidity in patients in advanced stages of infection. Subacute encephalitis demonstrating, the neuropathogenicity of HIV 1 constitute an human model for slow virus encephalitis. PMID- 2271987 TI - [Abuse and violence against the elderly]. AB - If the problem is not new in its nature, it happens frequently considering the increase of potential victims and aggressors. The elderly are special targets regarding to their fragility and life conditions. Abuse and neglect are related to physical, financial and care aspects. Common law aggressions happen on the public thoroughfare and at home. They lead frequently to delirium. In the bosom of the family 20% of old people are victims of physical brutality or moral cruelty. In the institutions their rate is poorly known and usually hidden. All the industrialized countries are preoccupied by this problem since a few years. Numerous speeches, journals and films are dedicated to these problems. The development of a real family politic in the elderly and an improvement of the education program for the personnel and an increase of the number of social care workers in the institutions may lead to a good prevention of abuse an neglect in the elderly. PMID- 2271988 TI - [Stereotaxic technics in expanding lesions of the brain stem]. AB - Stereotactic biopsies, according to the Talairach's system, define the histopathological data (nature, grading, spatial delimitation, evolutive potential) of brain stem lesions, precisely localized by computerized tomography scanner and magnetic resonance imaging. They are the more valued complement of the modern neuro-imaging and they prove the extreme polymorphism of theses lesions. According to this histological analysis and the volume of the lesions, it's possible to choose the best therapeutic procedure. PMID- 2271989 TI - [The efficacy of water ozonation on the inactivation of oocysts of Cryptosporidium]. AB - Cryptosporidium oocysts are currently found in surface waters. Their incomplete removal by sand filtration and their high resistance to chlorinated disinfectants make possible waterborne cryptosporidiosis outbreaks after drinking treated water. Because ozone is an alternative to chlorine for final drinking water disinfection the aim of our study was to determine the ozonation conditions able to eliminate the infectivity of oocysts. Feces from horses naturally infected by C. parvum were mixed with distilled water. The obtained suspension was clarified by passing through a graded series of four sieves (pore sizes, 315, 200, 125 and 63 microns). The clarified suspension was decontaminated by adding a 10% sodium hypochlorite solution. After a 10 minute contact time at room temperature, the chlorine residual was neutralised by the exactly requisite volume of a 0.01 N sodium thiosulfate solution. Oocysts in the suspension were purified by centrifugation and washing of pellets in distilled water. Oocysts in the finally obtained suspension were numerated by counting in a Malassez haemocytometer. Ozonated water containing dissolved ozone residuals ranging from 0.44 mg/l to 1.09 mg/l were inoculated with a number of oocysts ranging from 1.10(6) to 1.10(8). Contact times with ozone were 4.6 or 8 minutes. After destroying the ozone residual by sodium thiosulfate, ozonated oocysts were administered by oral route to male Sprague-Dawley rats weighing between 180 to 200 g and beforehand immunosuppressed by a regimen of 25 mg hydrocortisone acetate subcutaneously twice a week, 5 weeks before and 3 weeks after Cryptosporidium challenge. Oocyst shedding was daily controlled by phase contrast microscoy in smears of fecal suspension mixed with carbolfuchsine solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2271990 TI - Cholesterol isn't all bad. PMID- 2271991 TI - Susceptibility of epithelia to directive influences of mesenchymes during organogenesis: uncoupling of morphogenesis and cytodifferentiation. AB - Morphogenesis and functional cytodifferentiation are two major events in organogenesis, and normally they take place inseparably either in vivo or in vitro conditions. In this article, we reviewed a series of our recent results on mesenchymal-epithelial interactions in organogenesis of digestive organs, urogenital organs and the skin of avian and mammalian embryos, giving special attention to the importance of the responses of epithelia to the directive influences of mesoderms and also to the uncoupling of morphogenesis and cytodifferentiation, which has often been observed during the course of these studies. PMID- 2271992 TI - Qualitative comparison of protein production at different stages of hamster preimplantation embryo development. AB - The developmental pattern of protein production in hamster preimplantation embryos was investigated as a preliminary to studying the regulation of gene expression. Optimal radiolabelling of embryonic proteins was achieved by culturing a minimum of 40 embryos in 50 microliters of Hamster Embryo Culture Medium-2 for 2 h with 10 microCi of freshly lyophilized [35S]methionine. Proteins synthesized in vitro by different stages of hamster preimplantation embryos were analysed by one- and two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. There were striking changes in the protein profile following the first cleavage division and also lesser changes after the second cleavage division. There were no detectable qualitative changes in the protein profiles of 4-cell, 8-cell, morula and blastocyst stages although some quantitative difference existed between morula and blastocyst stages. These comparisons of protein profiles during different stages of embryo development indicate that in hamsters the onset of embryonic gene activation occurs during the 2-cell stage. PMID- 2271994 TI - Affinity purification of a 70K protein, a membrane protein relevant to sexual cell fusion in Dictyostelium discoideum. AB - Sexual cell fusion occurs between HM1 and NC4, heterothallic strains in Dictyostelium discoideum. A membrane component of HM1 cells with a molecular mass of 70 kDa (70K protein) has been shown to be implicated in cell fusion (Urushihara et al. (1988) Cell Differ. Dev. 25, 81-88). In the present study, 70K protein was partially purified using affinity Sepharose on which membrane proteins of NC4 cells were immobilized. Through this process, involvement of Ca2+ in the interaction of 70K protein with its receptor was suggested. Lectin staining of partially purified 70K protein indicated it to be a glycoprotein containing D-mannose and/or D-glucose residues. PMID- 2271993 TI - Stimulatory effects of retinal extract and fibroblast growth factor on lentoidogenesis in cultures of chick embryo neuroretinal cells. AB - A crude extract prepared from embryonic chick retina stimulates growth and particularly transdifferentiation into lens when added as a supplement to neuroretinal (NR) cultures in vitro. This effect is especially marked when using a medium (H) containing 5% horse serum, where growth factors are likely to be limiting. The level of delta-crystallin (lens marker) production in such cultures increases with the concentration of extract. Using extracts from earlier and later stages of retinal development, there is an age-dependent decline in the extent to which transdifferentiation is stimulated. However, such extracts have little effect on the activity of CAT, a neuronal marker enzyme. These effects are most probably mediated by growth factors present in the retinal extract acting upon Muller glial cells or their precursors in the NR cultures. In support of this suggestion, we show that purified fibroblast growth factor (but not epidermal growth factor) exerts similar effects on both culture growth and delta crystallin accumulation. PMID- 2271995 TI - Development of mouse germ cells in cultures of fetal gonads. AB - Mouse gonadal tissue was studied under various conditions of in vitro culture, with the aim of clarifying some of the somatic-cell influences that regulate the development of germ cells in the mammalian gonad. Gonadal ridges, with or without the adjacent mesonephric region, were removed from mouse embryos 10.5-12.5 days post coitum (dpc). In an organ culture system, the female ridges showed good development, with no masculinization. All germ cells entered meiosis at the expected time. Although some oocytes entered the growth phase, many primordial follicles were observed. 11.5- and 12.5-day male ridges formed testis cords, and the germ cells developed as T-prospermatogonia. In 10.5-day ridges, cells resembling Sertoli cells differentiated but did not form testis cords, and the germ cells entered meiosis. We conclude that full differentiation of the supporting cell lineage was not achieved when culture was begun at 10.5 dpc; our findings suggest that immature Sertoli cells neither form testis cords nor inhibit the entry of germ cells into meiosis. When the ridges were fragmented and cultured in gas-permeable dishes, the somatic cells grew out as a monolayer on which the germ cells rested. Under these conditions male germ cells did not enter meiosis and did not survive for more than a few days. Female germ cells entered meiosis. In contrast to the organ culture system, many of the surviving oocytes entered the growth phase during the second week of culture, reaching diameters of up to 60 microns. This suggests that normal follicular cell investment may play a crucial role in maintaining the oocyte in a state of developmental arrest. The growing oocytes showed the oocyte-specific expression of the enzyme glucose phosphate isomerase. It seems that the initiation and maintenance of both oocyte growth and oocyte-specific gene expression can take place in the absence of normal follicular cell investment. PMID- 2271997 TI - A morphological study of a human adenocarcinoma cell line (HT29) differentiating in culture. Similarities to intestinal embryonic development. AB - HT29 cells, a human adenocarcinoma cell line, when grown in Dulbecco's modified Eagle's medium (DMEM), form a multilayer of morphologically undifferentiated and unpolarized cells. However, when DMEM is replaced by RPMI medium, after 1-4 passages, a large amount of intracellular (ICL) and intercellular (ITCL) or secondary lumina (SL) are observed. These are detected in the light microscope and appear in the electron microscope as spherical structures embedded inside a multilayer of cells and bordered with microvilli. After 4-15 passages in RPMI, the cells retain the same pattern of cell growth but in addition exhibit apical brush-border microvilli and reveal a well developed belt of tight junctions. After 15 passages a single layer of polarized cells is clearly observed and a large number of 'domes' appeared. These results show that each of these culture types mimics morphologically specific stages described during intestinal ontogenesis between the 9th and the 16th week in the human embryo. PMID- 2271996 TI - Patterns of protein synthesis during Xenopus oocyte maturation differ according to the type of stimulation. AB - We examined the qualitative patterns of protein synthesis in fully grown prophase blocked oocytes of Xenopus laevis and after meiosis reinitiation accompanying maturation of the oocytes. Newly synthesized proteins labelled with [35S]methionine were run on isoelectric focusing gels and further separated in the second dimension on SDS-polyacrylamide slab gels. Three types of maturation inducer were compared: progesterone, considered as the natural inducer of Xenopus oocyte maturation, hCG (human chorionic gonadotropin) and insulin. Three polypeptides with apparent molecular masses of 37 kDa (pI 4.7-4.8), 78 kDa (pI 4.7) and 138 kDa (pI 4.6-4.7) were found to be always synthesized in all three types of stimulation, while the synthesis of a fourth one (molecular mass 116 kDa, pI 4.7) was arrested during oocyte maturation. Moreover, when the follicular cells surrounding the oocytes were part of the stimulating pathway, which is the case during hCG-induced maturation, an additional polypeptide was synthesized by the oocytes (molecular mass 106 kDa, pI 6.0-6.2). This polypeptide was not synthesized during progesterone- or insulin-induced oocyte maturation, two types of stimulation which do not require the presence of the follicular cells. The biological significance of the hCG-induced polypeptide, not necessary for oocyte maturation, is discussed. On the other hand, the four other modifications in protein synthesis taking place during all three types of maturation-inducing stimulation appear to be necessary for oocyte maturation, since oocytes which failed to mature in response to stimulation always missed one or several of these four polypeptides. PMID- 2271998 TI - Quantitative Doppler assessment of mitral regurgitation. PMID- 2271999 TI - Risk stratification in patients with non Q wave myocardial infarction: a role for thallium exercise testing. AB - The ability of maximal exercise thallium testing to stratify patients after non Q wave myocardial infarction was prospectively examined in 20 patients. Patients were enrolled in the study if there was no evidence of residual ischemia nor congestive heart failure during initial hospitalization. The thallium exercise test showed four patients to be at high risk, three of whom had successful revascularization. The remaining 16 patients were considered to be at low risk. There were no re-admissions for unstable angina, no myocardial infarctions and no deaths in the follow-up period (average 15 months). Thus patients with no evidence of early ischemia, no signs of left ventricular failure and a negative maximum thallium exercise test are at low risk following non Q wave myocardial infarction. PMID- 2272000 TI - Effect of rate-adapting atrioventricular delay on stroke volume and cardiac output during atrial synchronous pacing. AB - The need to adjust atrioventricular delay relative to pacing rate in atrial synchronous pacemakers was assessed in eight subjects treated for complete heart block (mean age 61 +/- 3.4 years). First, an inverse relationship between heart rate and PR interval was confirmed in two groups of healthy subjects and one group of patients recovering from myocardial infarction. Due to the limitations of the available pacemakers this relationship could not be precisely reproduced. Subjects with pacemakers performed an initial exercise test on a bicycle ergometer to determine heart rate response; this information was used in part 2 to program atrioventricular delay relative to heart rate. During a second exercise test, a rate-adapting atrioventricular delay was compared to a constant atrioventricular delay of 200 ms at matched heart rates. Cardiac output was measured noninvasively by impedance cardiography. The results of part 1 showed an abnormal pattern in the response of stroke volume to exercise in seven subjects. Part 2 results demonstrated no significant difference (P greater than 0.05) between a rate-adapting atrioventricular delay and a constant delay of 200 ms for heart rate, stroke volume, cardiac output, blood pressure or Borg scale. A trend towards increased stroke volume with a rate-adapting atrioventricular delay was observed. Stroke volume was 13% larger with a rate-adapting atrioventricular delay of 125 ms at a heart rate of 125 beats/min. These results suggest that subjects with atrial synchronous pacemakers have a variable stroke volume response to exercise. It appears that in these subjects the ability to increase heart rate is the key factor for raising cardiac output during exercise. PMID- 2272001 TI - Predictors of survival and sudden death in patients with stable severe congestive heart failure due to ischemic and nonischemic causes: a prospective long term study of 200 patients. AB - This prospective study of 200 stable outpatients with New York Hospital Association (NYHA) class III congestive heart failure on maximal medical therapy was done to determine which factors affect survival, to record the incidence of sudden death, and to identify prognostic features which characterize patients at high risk of sudden death. Congestive heart failure was due to coronary artery disease in 151 patients (76%). After an average follow-up of 40 months, 96 patients (48%) had died: 30 (15%) suddenly, 41 (22%) of low output, and 25 (13%) of other causes. Of the 30 patients dying suddenly 12 had autopsies, and acute myocardial infarction was found in nine. Of the 41 patients dying of low output 15 had autopsies, and recent myocardial infarction was found in five. Nine of the 25 patients dying of other causes died of acute myocardial infarction. Multivariate stepwise analysis revealed that severity of ventricular arrhythmias (modified Lown classification), exercise tolerance and left ventricular ejection fraction were the most important determinants of survival. In patients with coronary artery disease, complex ventricular arrhythmias detected by ambulatory Holter monitoring were frequent in all groups and were not clinically useful in predicting which of these patients were at a higher risk of dying suddenly. In contrast, patients without coronary artery disease who died suddenly had a higher incidence of nonsustained ventricular tachycardia and a tendency towards more frequent ventricular arrhythmias in general. The authors conclude that in ambulatory patients with stable NYHA class III heart failure, the severity of ventricular arrhythmias is a predictor of survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272002 TI - Cardiobacterium hominis endocarditis. AB - A 53-year-old man presented with nonspecific symptoms, evidence of aortic valve regurgitation and hepatosplenomegaly. Blood cultures grew Cardiobacterium hominis after 14 days of incubation. Endocarditis is caused by fastidious organisms such as C hominis in less than 5% of cases. To date approximately 40 cases of endocarditis due to this pleomorphic facultative anaerobic Gram-negative bacillus have been reported. C hominis is part of the normal human mouth flora. PMID- 2272003 TI - How physical education students see themselves. PMID- 2272004 TI - Bone tissue and physical activity. AB - Bones provide more than just a structural framework for the body. In reality, bone is a multifunctional tissue dependent on, and sensitive to, a wide variety of biological, biochemical and biomechanical stimuli. This complex system is highly responsive to the mechanical stresses imposed by gravity and muscular contractions. Animal studies as well as human cross-sectional and longitudinal studies all point to the importance of weight-bearing physical activity and mechanical loading as the prime modalities in the preservation of skeletal integrity. Lack of weight-bearing activity is extremely harmful to the skeleton. Loss of skeletal density in individuals subjected to various types of immobilization or under conditions of weightlessness is well documented. The role of physical activity in the maintenance of skeletal integrity is a topic of considerable current interest when the increasing incidence of skeletal fragility in the elderly is taken into account. PMID- 2272005 TI - Concentric and eccentric quadriceps torque in pre-adolescent males. AB - The purpose of this study was to evaluate the applicability of using the Kin Com (Chattecx Corp., Chattanooga, TN) isokinetic machine to measure concentric and eccentric quadriceps torque in a group of 12 healthy male volunteers aged 10-12 years. Each individual was tested by an experienced physiotherapist using a 60 degree per second velocity mode according to our standardized protocol. Average and peak torque values for concentric and eccentric contractions of the quadriceps were recorded; based upon the best of three maximum effort trials on each lower extremity. Retesting was performed on a randomly selected sub-group in an identical manner two weeks later. Our results showed no statistically significant difference between the original and retest values using the method error of repeated measurements and paired t-test analyses. Eccentric peak torque was greater on average than concentric. This was significant with p-values of 0.01 for the non-dominant quadriceps and 0.002 for the dominant side (paired t test). There was no significant difference between the dominant and non-dominant sides. In conclusion, eccentric muscle testing has been reliably quantitated for the first time in children. This study has shown a practical and reproducible method of quantitative muscle strength assessment. PMID- 2272006 TI - The effects of elastic tights on the post-exercise response. AB - It has previously been demonstrated that graduated compression stockings will affect the post-exercise venous lactate profile. To determine the effects of elastic tights on venous lactate levels and the post-exercise response, eight males completed three exercise bouts on a motor driven treadmill. Each subject ran on the treadmill for up to three minutes at 110% of his VO2max. The conditions for the three exercise bouts were: elastic tights worn during exercise and recovery, elastic tights worn only during exercise, and no elastic tights worn during exercise or recovery. Oxygen consumption, heart rates and venous blood samples, for lactate and hematocrit determination, were obtained at rest and at 5, 15 and 30 min post-exercise. Analysis revealed no significant differences (p greater than 0.05) in any of the above variables between the three trials at any of the measurement times. These results indicate that the use of elastic tights will not significantly affect the post-exercise response or circulating lactate levels. PMID- 2272007 TI - Effect of an exercise program on the perception of exertion in males at retirement. AB - To describe the association between perception of exertion and exercise, 138 men at retirement, mean age 62.7 years, were studied before and after a one-year program of exercise. VO2max and ratings of perceived exertion (RPE) using the Borg psychophysical scale were determined by a continuous exercise treadmill protocol to fatigue. The men were randomly assigned to an exercise program (n = 69) or control (n = 69). The program consisted of walking or jogging for 30 min, 3 times per week for one year. After training, the activity group showed a significant improvement in VO2max (12%). Linear regression analysis was used to relate RPE to selected physiological measurements for control and activity groups. The equations for the before and after training relationships were compared. Changes in the relationship of RPE vs VO2 and Ve, after training, were not significant for the activity group. However, the control group showed significant changes in these relationships at one year post retirement. For VO2 and Ve, ratings were 1-2 units higher than at time of retirement. Results indicate that perception of a physical task normally changes at retirement such that a given amount of exertion may seem subjectively greater. Results also suggest that a structured exercise program is successful at maintaining perception of task at pre-retirement levels. This maintenance of a low rating of perception may retard a reluctance to be physically active which often accompanies ageing. PMID- 2272008 TI - Perceptions of competence in physical education students. AB - This study sought to validate the Self-Perception Profile for College Students (Neemann and Harter, 1986) by investigating the perceived competence of physical education students as compared to students enrolled in other academic programs. Group One comprised 114 physical education students. Group Two consisted of 209 subjects enrolled in other academic programs. The Self-Perception Profile for College Students was administered to all subjects. Five scales (athletic, scholastic, social acceptance, appearance, and global self-worth) were analyzed. Factor analysis and internal consistency measures provided psychometric support for the scales. Separate ANOVAs calculated for each scale revealed that physical education students had higher perceptions of athletic competence than the other students. Males had higher perceptions of athletic and appearance competence, whereas females had higher perceived social acceptance. These findings are discussed in terms of psychometric issues, and the relationship between perceived competence and motivational patterns. PMID- 2272009 TI - Three-dimensional modeling by combining artificial with real data. AB - Issues arising in the graphics simulation of bone grafting and in the use of commercial libraries to create custom-designed models revolve on the ability to combine data defined in Volume Representation--as that generated by Computed Tomography scans--and user-defined data introduced in Boundary Representation--as vertices of polygons, for instance. To address these issues the authors propose a hybrid filling technique, which also processes conflicting adjacency information created by subsampling or digitization errors. A graphics experiment has been designed to illustrate the problems arising in the presence of objects defined partially in Volume and partially in Boundary Representation, and a method to handle them. PMID- 2272010 TI - Human face representation by means of polynomial expansion of the harmonic descriptors of tomograms. AB - A method is presented to obtain realistic modifications of faces represented as sequences of tomograms, to be used for geometrical modelling or for planning of plastic surgery. This method uses a mathematical model consisting of the harmonic expansion of tomograms whose harmonic parameters are represented by cubic spline functions of the z variable. Based on this model a three dimensional shape editor is proposed that allows for local modifications. The results obtained using tomograms of a plaster mould are presented. PMID- 2272011 TI - RGSS-ID: an approach to new radiologic reporting system. AB - RGSS-ID is a developmental computer system that applies artificial intelligence (AI) methods to a reporting system. The representation scheme called Generalized Finding Representation (GFR) is proposed to bridge the gap between natural language expressions in the radiology report and AI methods. The entry process of RGSS-ID is made mainly by selecting items; our system allows a radiologist to compose a sentence which can be completely parsed by the computer. Further RGSS ID encodes findings into the expression corresponding to GFR, and stores this expression into the knowledge data base. The final printed report is made in the natural language. PMID- 2272012 TI - Effect of field strength on susceptibility artifacts in magnetic resonance imaging. AB - In magnetic resonance imaging susceptibility artifacts occur at the interface of substances with large magnetic susceptibility differences, resulting in geometric distortions of the image at those boundaries. The susceptibility artifacts are often subtle on clinical images and if not carefully examined they may lead to misdiagnosis. Magnetic susceptibility artifacts are prevalent on the boundary of air-containing paranasal sinuses, as well as bone-soft tissue interfaces in the spinal canal. The appearance of these artifacts on images from three different magnetic field strength instruments, 0.3, 0.5, and 1.5 Tesla were studied. T1- and T2-weighted spin echo and gradient recalled echo pulse sequences were selected to image a water phantom containing substances of varying susceptibilities. The effects were also studied in MR images of the head in a normal human volunteer. At any given field strength the artifacts were more prominent in the gradient echo imaging than in the corresponding spin echo pulse sequence. As expected, the distortions were also greater at higher field strengths. The results in human subjects paralleled the findings in the phantom study. PMID- 2272013 TI - Findings of magnetic resonance imaging in cerebral venous occlusion: difference from hemorrhagic infarction. AB - A case of cerebral venous occlusion is reported. X-ray computed tomography showed a high-density lesion mimicking an intracerebral hemorrhage. In contrast, magnetic resonance images taken at the early clinical stage revealed a high intensity lesion in both T1- and T2-weighted images. Follow-up magnetic resonance images at the chronic phase revealed that the intensity of this lesion had changed to low in the T1-weighted image, while still being high in the T2 weighted image. These findings suggest that the lesion might be due to venous congestion produced by cerebral venous occlusion rather than hemorrhage into the cerebral parenchyma. PMID- 2272014 TI - Leiomyoma involving the gastrocolic ligament: CT demonstration. AB - A case of a large leiomyoma involving both the transverse colon and the greater curvature of the stomach is presented. Computed tomography (CT) demonstrated contiguous extension of the mass along the gastrocolic ligament. Although similar findings have been described in colonic and gastric carcinoma and in omental metastases, this is the first report in which these findings were due to a leiomyoma. PMID- 2272015 TI - A nursing model. PMID- 2272016 TI - The sacred and the secular in ICU. PMID- 2272017 TI - Unconditional care, Korean style. PMID- 2272018 TI - How to discover your own world view. PMID- 2272019 TI - A stunted faith or a sound world view? PMID- 2272020 TI - Neurobehavioral effects of toxicity due to metals, solvents, and insecticides. PMID- 2272021 TI - Hemiballismus. PMID- 2272022 TI - Akathisia, motility, and locomotion in healthy volunteers. AB - Apomorphine (10 micrograms/kg subcutaneously with oral domperidone 10 mg), oral sultopride (50 mg), and placebos were given to nine normal volunteers, using a Latin-square design and double-blind procedures. A battery of tests was applied before the dose, and after the dose after time lapses of 15, 45, 90, 105, 120, and 180 min. Spatiotemporal and dynamic gait parameters, gait stability, and modulations remained unchanged with all three treatments. Apomorphine induced repeated yawning in all subjects. Akathisia was observed in four of nine subjects with sultopride. Sultopride was associated with drowsiness and sleepiness on visual analog scales. Akathisia may be related to decreased dopaminergic activity in the prefrontal cortex and mesocortical dopamine system blockade. The imbalance between mesocortical and nigrostriatal dopaminergic systems might explain the fact that sultopride in our experiment modified spontaneous behavior but not volitional behavior. Thus, it is possible to discriminate between two types of increased motor activity, and motility must be distinguished from locomotor activity. PMID- 2272023 TI - Effect of a novel catechol-O-methyltransferase inhibitor, nitecapone, on the metabolism of L-dopa in healthy volunteers. AB - A new catechol-O-methyltransferase (COMT) inhibitor, nitecapone, was given in increasing doses of 0-100 mg concomitantly with L-Dopa/carbidopa (100/25 mg or 100/100 mg) to healthy male volunteers. Plasma concentrations of L-Dopa, 3-O methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), as well as the excretion of catecholamine metabolites in urine were followed to evaluate the changes in the metabolism of L-Dopa after nitecapone. Plasma concentrations of nitecapone and the soluble COMT activity in erythrocytes were also measured. The area under the plasma concentration-time curves (AUC) values for plasma nitecapone, L-Dopa and its metabolites were calculated. Nitecapone dose-dependently inhibited the soluble COMT activity in erythrocytes at 30 min after drug intake. Nitecapone slightly but significantly increased the relative bioavailability of L-Dopa. The AUC values of plasma 3-OMD decreased dose dependently after nitecapone, and those of HVA decreased less, whereas the AUC values of DOPAC increased significantly. The elevation of the dose of carbidopa from 25 to 100 mg increased the AUC value of L-Dopa, but the effect of nitecapone was not clearly modified. Nitecapone decreased the excretion of the methylated dopamine metabolites 3-methoxytyramine (3-MT) and HVA at an L-Dopa/carbidopa dose of 100/25 mg. At a dose of 100/100 mg, the excretion of metanephrine, in addition to 3-MT and HVA, was also significantly decreased by nitecapone. The biochemical changes in L-Dopa metabolism and erythrocyte COMT activity indicate that nitecapone is an active COMT inhibitor in humans, when given orally in single doses. The changes in L-Dopa metabolism by COMT inhibitor warrant further clinical studies in Parkinson's disease. PMID- 2272024 TI - Nigrostriatal damage is required for induction of dyskinesias by L-DOPA in squirrel monkeys. AB - We examined the ability of L-DOPA to induce dyskinesias in MPTP-treated and normal squirrel monkeys to establish whether the underlying neuropathology associated with parkinsonism is an absolute requirement or merely promotes the development of drug-induced dyskinesias. Administration of L-DOPA (5-40 mg/kg p.o., following a 60 min pretreatment with carbidopa 2.5-20 mg/kg p.o.) induced a range of dopamine-mediated behaviours including locomotor activity, stereotyped scratching, and climbing in both lesioned and nonlesioned animals. However, the dose-response curves showed a marked (three- to fourfold) shift to the left in lesioned animals, indicating behavioural supersensitivity. In contrast, L-DOPA induced dyskinesias were only observed in MPTP-treated monkeys. Doses required for induction of dyskinesias were lower than those required to induce climbing. These findings provide further evidence that nigrostriatal damage is essential for the genesis of L-DOPA-induced dyskinesias. PMID- 2272025 TI - Methylphenidate for reversal of drug-induced coma. PMID- 2272026 TI - Sexual dysfunction in Parkinson's disease. AB - Sexual functioning was investigated in 50 parkinsonian male and female patients using a questionnaire. A loss of sexual interest and functioning was reported in a high percentage of patients. Depression was not prevalent but 70% had some evidence of autonomic nervous system dysfunction that may be related to sexual dysfunction. It is concluded that the sexual function is frequently impaired in Parkinson's disease. PMID- 2272027 TI - In vitro and in vivo evaluation of US-NCI compounds in human tumor xenografts. PMID- 2272028 TI - New EORTC compounds. PMID- 2272029 TI - Novel anthracycline analogs. PMID- 2272030 TI - New cytostatics--more activity and less toxicity. PMID- 2272031 TI - Regional chemotherapy: different operative techniques and clinical results. PMID- 2272033 TI - Higher average received relative dose intensities of cyclophosphamide, methotrexate and 5-fluorouracil using a 24-hour method: implications for improved cure rates in breast cancer. PMID- 2272032 TI - Interstitial chemotherapy of experimental gliomas. AB - Two new approaches of interstitial (intratumoral) chemotherapy of gliomas are presented. Using s.c.-transplanted rat gliomas (G616) the therapeutic activity of biologically degradable polylactide rods as carriers for methotrexate was investigated. Carrier-mediated intratumoral chemotherapy was superior both to a systemic treatment and an intratumoral treatment with the free drug. The activity of the alkyllysophospholipids Et-18-OCH3 and BM 41.440 and of the alkylphosphocholine He-PC was investigated in a human glioma xenograft (T 406). All three compounds were highly active following intratumoral administration. PMID- 2272034 TI - Glutathione and detoxification. PMID- 2272035 TI - Modulation of 5-fluorouracil efficacy. PMID- 2272036 TI - Pentostatin (2'-deoxycoformycin) for the treatment of lymphoid neoplasms. PMID- 2272037 TI - Platinum compounds with estrogen receptor affinity. PMID- 2272038 TI - Hexadecylphosphocholine: a new and selective antitumor drug. AB - Interdisciplinary cooperation between basic and clinical research has resulted in the discovery and development of alkylphosphocholines, a new class of substances for the treatment of breast cancer. In contrast to most antitumor substances, the alkylphosphocholines do not attack the cell nucleus, but the cell membrane. This report presents a systematic study which, for the first time, provides a correlation between their chemical structure, antitumor efficacy and selectivity. Through an understanding of the metabolism of tumor growth inhibiting (ether) lysolecithins, the minimal structural requirements for the antineoplastic efficacy of these substances have been obtained. This knowledge was used to identify molecular structures which are more effective and less toxic for the organism. The active principle derived from a study of (ether)-lysolecithins active as antitumor agents represents a new class of compounds: the alkylphosphocholines. As reported here, hexadecylphosphocholine is the most promising candidate of this group of compounds. It has an extremely selective action against chemically induced, autochthonous rat mammary carcinomas. No loss of activity was observed when comparing oral and intravenous administration. Particularly striking (and favorable for long-term therapy) is the fact that immunosuppression and hematotoxicity were not found at drug concentrations which lead to complete tumor remissions. Results obtained from animal experiments have been confirmed by preliminary clinical investigations. PMID- 2272039 TI - Hexadecylphosphocholine in the topical treatment of skin metastases in breast cancer patients. AB - Widespread local recurrence of breast cancer, untreatable by surgery or radiation therapy, can present a serious therapeutic problem predominantly in patients refractory to systemic therapy. In a phase I trial hexadecylphosphocholine, a new agent with high membrane affinity and antineoplastic activity was applied topically to affected skin areas of breast cancer patients. The results provide evidence that hexadecylphosphocholine may be an active agent in the topical treatment of skin metastases. PMID- 2272040 TI - In vivo antitumor activity of ilmofosine. AB - Ilmofosine is a cytostatic/cytotoxic thioether phospholipid derivative. The in vivo anti-tumour activity of this compound was investigated in a methylcholanthrene (MethA)-induced fibrosarcoma and in the 3Lewis-lung carcinoma systems, respectively. Ilmofosine showed antineoplastic and antimetastatic properties at oral doses ranging from 0.625 to 40 mg/kg/day. Combination of Ilmofosine (p.o.) together with either cyclophosphamide (p.o.) or cis-DDP (i.v.) resulted in synergistic effects in vivo. These results demonstrate the in vivo antitumour activity of Ilmofosine in two tumour systems. The data indicate that direct cytostatic/cytotoxic effects of Ilmofosine are mainly responsible for its antitumour activity in vivo and which are increased by other cytotoxics. PMID- 2272041 TI - Cisplatin-linked phosphonates in the treatment of the transplantable osteosarcoma in vitro and in vivo. PMID- 2272042 TI - New tumor-inhibiting metal complexes. PMID- 2272043 TI - High-dose versus intermediate-dose cytosine arabinoside in combination with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia- preliminary clinical and pharmacological data of a randomized comparison. AB - The present randomized trial addressed the pending question whether cytosine arabinoside (AraC) should be given at high or intermediate dose to patients with relapsed or refractory acute myeloid leukemia. Based upon the previously established regimen of the sequential administration of AraC and mitoxantrone (S HAM) patients below 60 years of age were randomized to receive AraC at either 3.0 g/m2 vs. 1.0 g/m2 per dose while older patients were randomly assigned to either 1.0 g/m2 or 0.5 g/m2 AraC. Concurrent pharmacokinetic analyses were performed to determine the plasma AraC pharmacokinetics as well as the intracellular AraCTP peak concentrations and retention times. At the present stage 65 patients are evaluable for response and toxicity. Complete remissions were achieved at similar frequencies for patients treated with 3.0 g/m2 or 1.0 g/m2 AraC with 56% and 50%, respectively. Reasons for failure were different, however, with a higher incidence of resistant disease in patients treated with 1.0 g/m2 AraC and more early deaths in the higher dose treatment group. Pharmacokinetic studies indicated a homogeneous distribution of AraC plasma concentrations but a substantial interpatient variability for intracellular AraCTP peak concentrations and retention times. PMID- 2272044 TI - High-intensity therapy versus low-intensity therapy in advanced breast cancer patients. AB - The aim of this study was to evaluate the significance of response to the first two cycles of FEC (5-fluorouracil, 4-epirubicin, cyclophosphamide) in patients with advanced breast cancer. A total of 99 patients entered the study. They showed either high risk criteria and were previously untreated or showed low risk criteria and were pretreated by hormonal therapies. Eighty-two patients were evaluable. In 22 (27%) who had disease progression despite two cycles of FEC, further therapeutic attempts proved ineffective, the median survival being 2.8 months. The remaining patients responded either by stable disease (SD, n = 29; 35%), by partial or by complete remission (PR, CR, n = 31; 38%). These 60 patients were randomized to two regimes of maintenance therapy: FEC every 3 weeks or LMF (leukeran, methotrexate, 5-fluorouracil) every 6 weeks. The subsequent course of the disease was not different in both arms. It was neither influenced by the quality of early response, i.e. SD, PR, CR, nor by the intensity of chemotherapy. The prognostic impact of early response to two cycles of FEC proved to be higher than other prognostic parameters in the patients examined. Thus, early response may serve as a valid guide to adapt maintenance chemotherapy in individual patients with advanced breast cancer. PMID- 2272045 TI - Modulation of cytotoxicity of cytostatic drugs by hemodialysis in vitro and in vivo. AB - For most cytotoxic substances there are no established guidelines on how to deal with overdosage. Little is known about the dialysability of cytostatic drugs. To obtain further information, human plasma was incubated with cytostatic drugs and dialysed in vitro, using 'minimodules' with capillaries identical to those in clinical use. Cytotoxicity before and after dialysis was measured in a biological test system using permanent human lymphoblast cultures (LS2). The 20 cytostatic drugs studied were categorized as follows: (1) Dialysability in vitro. Good: methotrexate (MTX), 5-fluorouracil (5-FU/5-FUdR), cytarabine (ARAC), actinomycin D (DACT), mitomycin C (MMC), 4-OH-cyclophosphamide (4-OH-CPM), ifosfamide (IFO), melphalan (L-PAM), dacarbazine (DTIC), cisplatin (DDP). Intermediate: Adriamycin (ADM), 4'-epi-doxorubicin (4'-EA), carmustine (BCNU). Ineffective: daunorubicin (DNR), vincristine (VCR), vinblastine (VBL), vindesine (VDS), etoposide (VP-16), teniposide (VM-26), mitoxantrone (MITOX). These in vitro results cannot be transferred automatically into the in vivo situation because of specific drug distribution and metabolic rates. Considering pharmacokinetic data from the literature, the following recommendations can be made for practical clinical purposes. (2) Detoxification by hemodialysis in vivo. Possibly effective: MTX, 5 FU, MMC, CPM, IFO, L-PAM, BCNU, DTIC. Ineffective: ADM, 4'-EA, DNR, MITOX, DACT, VP-16, VM-26, VCR, VBL, VDS, ARAC, DDP. PMID- 2272046 TI - Antiemetic action of 5-HT3 receptor antagonists: review of preclinical and clinical results with ICS 205-930. AB - These results thus indicate, that ICS 205-930 is a very effective antiemetic for cancer chemotherapy-induced emesis in man. Given as a single dose prior to the chemotherapeutic agent, ICS 205-930 inhibits emesis and nausea for at least 24 hr. Together with the lack of extrapyramidal side-effects, these properties of ICS 205-930 indicate a clear superiority to the current therapeutic standard metoclopramide. PMID- 2272047 TI - Batanopride (BMY-25801): a new 5-HT3 receptor antagonist for the prevention of cancer chemotherapy-induced emesis. PMID- 2272049 TI - Tumor heterogeneity and chemosensitivity to cyclophosphamide, vinblastine and hexadecylphosphocholine. PMID- 2272048 TI - Combination chemotherapy in radically operated advanced ovarian cancer. PMID- 2272050 TI - The use of haemoregulatory peptides (pEEDCK monomer and dimer) for reduction of cytostatic drug induced haemopoietic damage. AB - We have previously shown that the stem cell inhibitory peptide pGlu-Glu-Asp-Cys Lys (pEEDCK monomer) leads to a good tolerance of otherwise lethal multiple ara-C doses and an increased survival of ara-C + peptide treated mice. This effect was due to the prevention of drug-induced CFU-S proliferation, thus keeping stem cells in a quiescent state insensitive to ara-C. Here we show that the pEEDCK monomer also inhibits stem cell proliferation after clinically relevant (non lethal) ara-C doses. This leads to a sustained (100%) stem cell number in the femoral bone marrow, which was greatly reduced without protective peptide treatment (27%). We have measured the kinetics of influx of CFU-S into the empty S-phase (after two consecutive ara-C injections). This influx reached peak levels of 60-70%; pEEDCK treatment reduced it to 25-30%. Due to its cysteine content the pEEDCK monomer is easily oxidized and forms a symmetric disulfide-bonded dimer (pEEDCK)2. This dimer is a potent stimulator of haemopoiesis. Various modes of protective peptide treatment (monomer and dimer) were investigated in conjunction with a standardized protocol of 2 x 300 mg/kg ara-C given 12 h apart. (a) ara monomer-ara: The administration of pEEDCK-monomer 2 h before the second ara-C injection retarded the onset of neutropenia, shortened its duration and improved recovery after depression. The degree of short-term neutropenia was not changed. (b) ara-ara-HN2-dimer: Post chemotherapy infusion of the stimulatory (pEEDCK)2 dimer led to considerable increases of progenitor levels (6.8 CFU-GM/1000 bone marrow cells vs. 1.2 CFU-GM/1000 in normal mice) 2 days after cytostatic treatment when CFU-GM were not detectable in unprotected mice. This increase was followed by greatly elevated granulocyte counts (8000 PMN/mm3 vs. 750 PMN/mm3 in normal mice). In the dimer-treated mice, up to 75% of the peripheral leukocytes were mature PMN (normal, 10%). (c) ara-monomer-ara-dimer: ara-C and monomer treatment as above (a) followed by dimer infusion led to complete protection of haemopoiesis. Mice treated with the protective pEEDCK monomer plus stimulatory dimer did not develop the leukocyte depression seen in unprotected animals. Our results show that the haemoregulatory peptide monomer and dimer can be used to improve the haematological status of mice treated with clinically relevant doses of cytostatic drugs (anti-metabolite and alkylating, alone and in combination). The pEEDCK monomer and dimer are equally active also on human haemopoietic cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2272051 TI - Two-phase radioimmunotherapy using bispecific monoclonal antibodies (bs MAbs). PMID- 2272052 TI - Pitfalls in the clinical application of monoclonal antibodies in malignant melanoma: modulation by and impaired accessibility of antigens to monoclonal antibodies. PMID- 2272053 TI - Antibody targeted therapy in cancer: comparison of murine and clinical studies. AB - Antibody targeted therapy can be effective in animal models of cancer. Treatment has been less successful in man, though some responses are reported. Understanding the distribution of antibody in man and animals shows how toxicity may be minimized and patients selected for therapy on the basis of efficient antibody localization in the tumour. PMID- 2272054 TI - Management of the patient with the Wolff-Parkinson-White syndrome. AB - Patients with ventricular preexcitation may have symptomatic arrhythmias (Wolff Parkinson-White syndrome) which can range from life-threatening, to disabling symptoms or minimal symptoms. Individuals may also be entirely asymptomatic. A rational approach to the management of these individuals is therefore dependent on the clinical circumstances. This review discusses the value and limitations of some of the available noninvasive and invasive investigations which may contribute to the successful management of these patients. In general, investigations are useful for establishing the diagnosis, identifying those patients at risk from life-threatening arrhythmias and providing a rational basis for therapy. The available pharmacologic and nonpharmacologic therapeutic options are discussed. PMID- 2272055 TI - Clinical management of patients with nonsustained ventricular tachycardia: what do we really know? AB - The management of patients with nonsustained ventricular tachycardia remains one of the most difficult tasks facing the practicing cardiologist. This common arrhythmia is a marker for death and morbid events in patients with a variety of forms of heart disease, but there is as yet no conclusive evidence that its suppression confers benefit. This paper will review the methods now available to risk stratify patients who have repetitive forms on electrocardiographic monitoring, their advantages and limitations. We will also review some of the trials which have attempted to prove that arrhythmia suppression improves survival. Finally, we will try to provide some recommendations to the clinician, based on what we know about this common arrhythmia. Though we will concentrate our attention on ischemic heart disease, we will briefly discuss the preferred management of patients with other forms of heart disease in whom the presence of nonsustained ventricular tachycardia has prognostic significance. We would like to emphasize that this is a rapidly changing field, and that treatment approaches will necessarily change, based on the results of ongoing clinical trials. The physician must not rigidly adhere to any treatment policy, but rather alter his or her approach based on the development of new information. PMID- 2272056 TI - Current application of implantable cardioverter-defibrillators in the management of malignant ventricular tachyarrhythmias. AB - Several studies have uniformly demonstrated a marked reduction in expected arrhythmic/sudden death rates in patients with either drug-refractory sustained ventricular tachycardia, ventricular fibrillation or survivors of cardiac arrest following the implantation of cardioverter-defibrillators (ICD). Significant advances in these devices over the past 10 years have permitted programmability and demand pacing. There has been sophistication in tachycardia detection and the characteristics of the delivered electrical therapy. Programs to reconfirm the arrhythmic event, sensing parameters for rate, electrogram amplitude, data storage, interrogation and morphology are available in some devices. Some models will permit both antitachycardia pacing as well as defibrillation functions and choice of shock waveforms as bidirectional and biphasic shocks. Endocardial lead systems using smaller and more flexible electrodes may obliterate the need for thoracotomy. It appears that ICD therapy will form a significant component in antiarrhythmic therapy in the future. PMID- 2272057 TI - Management of Stokes-Adams syndrome. AB - Stokes-Adams attacks are related to paroxysmal or chronic atrioventricular (AV) block (50-60%), sinoatrial (SA) block (30-40%) or paroxysmal tachycardia or fibrillation (0-5%). In between attacks most patients present with sinus rhythm, a large part with widened QRS complex. A minor proportion of patients present with chronic AV block. ECG is very rarely normal. Diagnosis is based on ECG recording during fainting. In patients with sinus rhythm and bundle-branch block or AV block, ECG monitoring should be performed in hospital, since Stokes-Adams syndrome in these patients is a potentially life-threatening disease. In sick sinus syndrome where the suspected arrhythmia is not life-threatening, ambulatory ECG by Holter monitoring can be performed to establish the diagnosis. In cases where ECG monitoring leaves doubt, an electrophysiologic study including His bundle electrography and sinus node recovery time may support the diagnosis, although normal findings do not preclude the diagnosis. Pacemaker implantation should be performed in Stokes-Adams syndrome, as oral drug treatment is ineffective. The dual-chamber pacemaker presents the advantages of both physiological heart rate and AV synchrony, but has troublesome side effects. Most patients with tachycardia/bradycardia syndromes require supplementary anti arrhythmic treatment, and in some patients additional long-term anticoagulation should be considered. PMID- 2272058 TI - Differential diagnosis of supraventricular and ventricular tachycardia. AB - Few if any medical decisions are of more urgent importance than the accurate discrimination between ventricular tachycardia and supraventricular tachycardia with ventricular aberration, and probably no common diagnosis is more often missed. Yet the distinction can often be readily made with a knowledge of the several clues here described. These include QRS morphology, polarity and width; and clinical or electrocardiographic evidence of independent atrial activity. Knowledge and application of these serviceable clues should enable the clinician to establish a correct diagnosis in 90% of wide-QRS tachycardias without resorting to invasive studies. PMID- 2272059 TI - Management of survivors of out-of-hospital cardiac arrest. AB - Sudden cardiac death is a major cause of death in the western world. Since a 1 year recurrence rate of 30% is expected in survivors of sudden death, treatment is mandatory. If an apparent cause (e.g. proarrhythmia or acute ischemia) exists, treatment is generally directed at its alleviation. However, in most patients no obvious cause is found. Both noninvasive and invasive diagnostic procedures are employed to uncover treatable etiologies. If a treatable cause is not found, an electrophysiological study may be employed to tailor antiarrhythmic therapy. At this point, many patients still cannot be offered an adequate antiarrhythmic treatment. For these patients, amiodarone, antiarrhythmic surgery or an implantable defibrillator may be appropriate options. Algorithms for diagnostic and therapeutic interventions in survivors of sudden cardiac death are delineated. PMID- 2272060 TI - Use of programmed stimulation in identifying patients at high risk for sudden cardiac death. AB - Sudden cardiac death accounts for 60% of the total cardiovascular mortality in the United States. Individuals after myocardial infarction or with chronic left ventricular dysfunction are known to be at increased risk. Noninvasive studies have been applied to these populations, but the predictive accuracy of these tests is low. Investigators have used programmed stimulation attempting to identify patients at increased risk and guide their treatment. The prognostic utility of programmed ventricular stimulation for prediction of sudden cardiac death in these populations is reviewed. PMID- 2272061 TI - Ablation of the slow-conduction area in chronic ventricular tachycardia. AB - The ablation techniques, which derive from surgical approach in the treatment of ventricular tachycardia, were originally based on the modification of conduction in the so-called site of origin of the arrhythmia. A reentrant tachycardia involves two areas of conduction, one which consists of normal tissue, and the other with slow-conduction properties isolated from the previous structure. We now think that a more appropriate place to deliver the shock should be the area of slow conduction. The purpose of this paper is to review the main electrophysiological characteristics of this tissue, which could be interesting markers to identify the site where the shock should be delivered. PMID- 2272062 TI - Supraventricular tachycardia: diagnosis and treatment. AB - Specific mechanisms of supraventricular tachycardia include sinoatrial, intra atrial, atrioventricular (AV) nodal as well as concealed and manifest bypass tract reentry. In dual pathway reentry, at least one of the pathways involves the AV node, usually the slow pathway and the other pathway, perinodal fibers within the atria. Localization of the perinodal fibers is critical for ablative procedures to eliminate AV nodal tachycardias. Other mechanisms of supraventricular tachycardia include chaotic atrial tachycardia and automatic atrial tachycardia with and without AV block. However, drug therapy includes intravenous adenosine 6 mg, as well as the older standbys of digoxin, calcium and beta-blocking agents, and type 1a and 1c antiarrhythmias. In resistance cases, amiodarone is usually effective. However, for incessant supraventricular mechanisms, catheter or surgical ablative techniques are recommended to eliminate long-term drug administration. PMID- 2272063 TI - Regional pulse wave velocities in hypertensive and normotensive humans. AB - STUDY OBJECTIVE: The aim was to compare regional wave transmission and reflection properties along the aorta in age matched normotensive and hypertensive subjects. DESIGN: Simultaneous upstream and downstream micromanometer pressures were recorded at five regions from the ascending aorta to the iliac artery. Recordings were made in the baseline condition in both groups and during sustained isometric handgrip exercise in the normotensives to see if increasing the blood pressure to hypertensive levels would eliminate baseline differences between the two groups. SUBJECTS: Only subjects who had no coronary or valvular heart disease were studied. Normotensive subjects (n = 8) were selected from those undergoing electrophysiological testing whose blood pressures were consistently in the normal range (systolic less than 140, diastolic less than 90 mm Hg). Age matched hypertensive subjects (n = 17) were those in whom secondary causes of hypertension were excluded and who had repeated measurements of raised blood pressure. MEASUREMENTS AND RESULTS: In each region pulse wave velocity was estimated from the simultaneous upstream and downstream pressure records using the foot to foot method, and apparent phase velocity was obtained from Fourier analysis of the two pressures. The intensity of wave reflections was judged by the magnitude of fluctuations of the harmonics of apparent phase velocity about the mean of the higher frequency harmonics. In both groups in the baseline state there were regional variations in the pulse wave velocity with the lowest values occurring just proximal to the renal arteries and highest values occurring in the iliac artery. Likewise, in both groups the extent of wave reflections varied regionally--pronounced reflections were seen in the ascending aorta and from just proximal to the renal arteries to the aortic bifurcation but not in the mid thoracic or iliac regions. The hypertensives had higher pulse wave velocity than normotensives only in the iliac artery (780 v 567 cm.s-1) and had more reflections in the three regions in which reflections were evident. Although handgrip in the normotensive group eliminated regional differences in pulse wave velocity between the groups, reflections were still greater in the hypertensives. CONCLUSIONS: Essential hypertension affects the regional properties of the aortic wall. These alterations are manifested by increased peripheral wave-speed and increased wave reflections along the aorta. The differences in wavespeed but not reflection properties are eliminated when the pressures are matched by handgrip, suggesting that factors other than the level of blood pressure per se are responsible for the alterations in reflection properties. PMID- 2272064 TI - Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts. AB - STUDY OBJECTIVE: The aim was to investigate the role of intracellular pH (pHi) and ion exchange on the functional recovery of perfused hearts isolated from normal (N) rats either receiving or not receiving amiloride (an Na+/H+ exchange inhibitor), and from STZ induced diabetic (D) rats with decreased Na+/H+ exchange activity. DESIGN: Working heart preparations were submitted to a zero flow ischaemic period of 30 min at 37 degrees C and then reperfused for 30 min. The time course of pHi decline during ischaemia and of recovery on reperfusion was followed by means of 31P-NMR. MEASUREMENTS AND MAIN RESULTS: In N hearts without amiloride, ischaemia caused a progressive decrease in pHi. This was slightly, although not significantly, more abrupt in N hearts receiving amiloride. D hearts showed a slower fall in pHi, but the mean value reached after 30 min did not differ significantly from that of normal hearts. pHi recovery on reperfusion was markedly slower in the D hearts compared to N hearts. The mean value reached after 30 min did not differ significantly from that of N hearts. pHi recovery was also markedly slower in N hearts exposed to amiloride during both ischaemia and reperfusion. The higher functional recovery on reperfusion, as assessed by the recoveries of aortic flow and stroke volume, was observed for those hearts with slower pHi recovery. Improved recoveries of aortic flow and stroke volume as compared to normal non-treated hearts were 34% and 21% for the diabetic hearts, and 22% and 40% for the normal hearts receiving amiloride. CONCLUSIONS: The comparison of data from diabetic rat hearts with reduced activity of the Na+/H+ exchange process v normal hearts with pharmacological block of the exchanger provide support for a critical role of the Na+/H+ exchanger in the initial stage of reperfusion. PMID- 2272065 TI - Myocardial ischaemia induced by endothelin in the intact rabbit: angiographic analysis. AB - STUDY OBJECTIVE: The aim was to clarify the effects of endothelin on coronary vasculature in the intact rabbit by coronary angiographic examination. DESIGN: By selective coronary angiography bolus injections of various amounts of endothelin (0.01-1 nmol) were given into the right coronary artery of anaesthetised rabbits. The preventive effects of nifedipine on endothelin induced myocardial ischaemia were examined. SUBJECTS: Adult male Japanese white rabbits (2.7-3.5 kg, n = 29) were used for in vivo and in vitro studies. MEASUREMENTS AND MAIN RESULTS: Intracoronary administration of 0.1 nmol endothelin led to the delayed filling of contrast medium into the distal coronary artery and the sustained retention of contrast medium in both large and small coronary arteries, associated with distinct ST elevation in leads II, III and aVF on the electrocardiogram. However, endothelin produced no evident constriction at any site in the large epicardial coronary arteries. Intracoronary administration of glyceryl trinitrate (50 micrograms) or nifedipine (5 micrograms) failed to reverse myocardial ischaemic changes induced by endothelin. Pretreatment with intravenous administration of nifedipine (3 micrograms.kg-1) partially inhibited the endothelin induced vasoconstrictor effect on small coronary arteries and subsequent ischaemic changes. In isolated coronary arterial preparation, endothelin produced long lasting contraction in a dose dependent manner [ED50 = 3.7 (SEM 1.8) nM]. Pretreatment with nifedipine inhibited the maximum contraction induced by endothelin, but did not affect the threshold dose or the half maximal effective dose (ED50). Endothelin (0.1 microM) per se did not produce aggregatory responses of rabbit platelets. CONCLUSIONS: Endothelin induced myocardial ischaemia cannot be ascribed to vasospastic constriction of large coronary arteries nor to platelet thrombi, but diffuse constriction of small coronary arteries occurs in the intact rabbit. PMID- 2272066 TI - Interplay between adrenaline and interbeat interval on ventricular repolarisation in intact heart in vivo. AB - STUDY OBJECTIVE: The aim was to examine the hypothesis that an interaction between adrenaline and change in heart rate may alter the normal time sequence of ventricular repolarisation (and hence refractoriness) in a manner that (1) may favour arrhythmia formation, (2) may partly explain conflicting reports of the effect of adrenaline, ie, there are two opposing effects on action potential duration, and (3) be relevant to T wave abnormalities that sometimes occur in normal people. DESIGN: As a measure of the time course of repolarisation, monophasic action potentials were recorded simultaneously from three epicardial sites in the porcine heart (left ventricular apex, left ventricular base, and mid right ventricle). During steady state pacing, test pulse intervals were interposed at progressively shorter intervals in order to construct restitution curves. MEASUREMENTS AND MAIN RESULTS: Adrenaline infusion (0.4-1.5 micrograms.kg 1.min-1) resulted in earlier repolarisation in the beats after shorter interbeat intervals, and delayed repolarisation after longer interbeat intervals, tending to turn the restitution curve anticlockwise (ie, there were two opposing effects on action potential duration). The effects were not homogeneous between regions. To show this inhomogeneity, pairs of monophasic action potentials from different regions were subtracted using a differential input amplifier to produce an ECG like waveform at the amplifier output. The resulting T wave was thereby a measure of the time difference in repolarisation between the monophasic action potentials from which it was derived. The inhomogeneity of repolarisation induced by adrenaline and rate change was reflected in the morphology of this derived T wave, particularly at early (premature) beats. These T wave changes correlated closely with the true T wave changes in bipolar electrograms recorded between the same recording sites (R = 0.89; p less than 0.0001). CONCLUSIONS: These results show that adrenaline altered the normal relationship between interbeat interval and the timing of repolarisation. The effect was not homogeneous and when regional differences were observed they were reflected in changes in T wave morphology. These were marked at short intervals. It is possible that in addition to increased excitability observed with adrenaline, a combination of raised sympathetic activity and early beats predisposes to arrhythmias by exaggerating dispersion of repolarisation. PMID- 2272067 TI - Effect of pre-existing four hour coronary stenosis on ventricular arrhythmias during a subsequent 10 minute occlusion in dogs. AB - STUDY OBJECTIVES: The aim was to assess the effect of pre-existing coronary stenosis on ventricular arrhythmia during subsequent acute coronary occlusion. DESIGN: Dogs with a 4 h intact interval followed by a 10 min occlusion of left anterior descending coronary artery (group A) were compared for ventricular arrhythmias with dogs with a 4 h stenosis of the same artery followed by a 10 min occlusion (group B). Myocardial blood flow was measured in the ischaemic myocardium using the H2 gas clearance method to exclude dogs with good collateral flow (myocardial blood flow greater than 11.0 ml.min-1.100g-1). EXPERIMENTAL ANIMALS: 35 mongrel dogs of either sex, weight range 11-26 kg, were used in the experiments (group A, n = 17; group B, n = 18). After exclusion of dogs with good collateral circulation there were 11 dogs in group A (subgroup A1) and 12 dogs in group B (subgroup B1). MEASUREMENTS AND MAIN RESULTS: The incidence of ventricular fibrillation was lower in group B (pre-existing stenosis) than in group A during the 10 min occlusion, though there was no difference in numbers of ventricular premature beats. Maximum ST segment elevation and maximum conduction delay were less in group B than in group A, but myocardial blood flow did not differ during the 10 min occlusion. In the subgroups the incidence of both types of ventricular arrhythmia was lower in subgroup B1 during the 10 min occlusion, while the maximum ST segment elevation and maximum conduction delay were less, and myocardial blood flow was greater. CONCLUSIONS: Pre-existing 4 h coronary stenosis causes the development of collateral flow and reduces the incidence of ventricular arrhythmias during subsequent occlusion. PMID- 2272068 TI - Characterisation of decay of frequency induced potentiation and post extrasystolic potentiation. AB - STUDY OBJECTIVE: The aim was to elucidate the processes underlying the beat by beat decay of frequency induced and post-extrasystolic potentiation. DESIGN: The ventricular pacing protocol consisted of a "priming period" followed by a "decay" period of pacing at 1 s intervals, characterised by a decaying potentiation of left ventricular (LV) dP/dtmax; these were identified as test beats 1,2,3,4,5. The magnitude of potentiation of test beat 1 (P1) was increased both by increased priming frequency (frequency potentiation) and by alternately shorter priming intervals (paired pulse stimulation) at a given average frequency (post extrasystolic potentiation). The exponential decay constant (P2) and the asymptotic value (P3) were determined and compared with the measured values and with the slope of the linear relationship between the contractility of one beat and that of the preceding beat. The lowest values after decay were related to the magnitude of preceding potentiation. EXPERIMENTAL MATERIAL: Six anaesthetised dogs with induced heart block and beta adrenergic blockade were used. Beat to beat interval was controlled by ventricular pacing from a programmable stimulator. MEASUREMENTS AND MAIN RESULTS: Contractility of each beat was assessed from maximum rate of rise of LV pressure (LVdP/dtmax) obtained from an intraventricular micromanometer. The asymptotic value of the exponential fit to the decay of potentiation (P3) was found to be below the measured nadir value, which was followed by an increase in LVdP/dtmax to the final steady state value P4. The decay constant (P2) was found to be equivalent to the natural logarithm of the slope of the linear relationship between the contractility of one beat and that of the preceding beat; it was unaffected by priming frequency or interval at a given average priming frequency. The asymptote P3 was inversely related to P1. CONCLUSIONS: P1 was interpreted as the expression of accumulation of activator in an internal release store; P3 was interpreted as a manifestation of negative feedback control of activator entry by the released activator itself, and the slow recovery to P4 as due to the slow lengthening of action potential duration and/or recovery from accumulation of an intracellular metabolite or ion. PMID- 2272069 TI - Positive inotropy linked with class III antiarrhythmic action: electrophysiological effects of the cardiotonic agent DPI 201-106 in the dog heart in vivo. AB - STUDY OBJECTIVE: The aim was to investigate whether the positive inotrope DPI 201 106 prolongs ventricular monophasic action potential duration and refractoriness in vivo without affecting conduction, thus possessing class III antiarrhythmic characteristics in vivo. DESIGN: Electrophysiological and haemodynamic effects of DPI 201-106 (0.5, 1.0, and 2.0 mg.kg-1 intravenously) were studied at spontaneous heart rate and at three different paced cycle lengths (353, 300, and 261 ms). The following were recorded: monophasic action potentials from right ventricular endocardium; intracardiac conduction times by His bundle electrocardiography; refractoriness by programmed electrical stimulation; and left ventricular (LV) pressures. SUBJECTS: Seven mongrel dogs of either sex, weighing 14-24 kg, were studied under sodium pentobarbitone anaesthesia. MEASUREMENTS AND MAIN RESULTS: DPI 201-106 prolonged ventricular monophasic action potential duration and refractoriness dose dependently and most effectively at long cycle lengths, with no effect on intracardiac conduction times. DPI 201-106 increased LV dP/dtmax, while LV systolic and end diastolic pressures were unchanged both during spontaneous and paced heart rate. DPI 201-106 decreased spontaneous heart rate. CONCLUSIONS: Prolonged monophasic action potential duration and increased refractoriness, with no effect on conduction, indicate class III antiarrhythmic action of DPI 201-106 in vivo. PMID- 2272070 TI - Taurine depresses INa and depolarises the membrane but does not affect membrane surface charges in perfused rabbit hearts. AB - STUDY OBJECTIVE: The aim was to determine whether taurine influences the membrane surface charges in cardiac muscle. DESIGN: Screening of the negative charges at the outside surface of the membrane results in a shift of the steady state inactivation of the sodium system towards less negative potentials. This feature was used to study eventual effects of taurine on surface charges and the data were compared to the known influence of varying extracellular calcium. EXPERIMENTAL MATERIAL: New Zealand rabbits (6-7 weeks, 1.25-1.75 kg) were anesthetised and the hearts were rapidly excised and perfused with the Langendorff technique. MEASUREMENTS AND MAIN RESULTS: Standard microelectrodes were used to determine the effects of 20 mM taurine and varying Ca concentrations (from 0.3 to 5.0 mM) on action potential parameters. The resting potential was varied by changing extracellular K between 2.5 and 10 mM. Taurine significantly depolarised the membrane by about 3 mV between 5 and 10 mM Ko but not at 2.5 mM; the maximum rate of depolarisation (dV/dTmax) decreased significantly at all Ko except at 10 mM where taurine caused arrhythmias or cardiac arrest. The dV/dTmax upsilon resting potential relationship (a measure for the steady state sodium current inactivation) was not changed by taurine, but the current was depressed as a function of membrane potential, the depression being more pronounced at more positive membrane potentials. An increase in Cao from 0.3 to 5.0 mM displaced the half maximal value of the dV/dtmax upsilon resting potential relationship from 79 to -67 mV, showing that the screening effect of Ca on the negative charges at the outside surface of the membrane could be detected with this experimental approach. CONCLUSIONS: The decrease of the fast Na current by taurine can explain the arrhythmias observed at 10 mM external potassium, whereas the surface charges of the glycocalix were not affected. PMID- 2272071 TI - 5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. AB - STUDY OBJECTIVE: The aim of the study was to investigate the receptor events that mediate the vascular effects of 5-hydroxytryptamine (5-HT) on human coronary arteries, since 5-HT has long been thought to play a role in coronary artery vasospasm. DESIGN: Recently available selective receptor agonists and antagonists were used to examine the 5-HT receptor subtypes present in human epicardial coronary arteries using in vitro organ baths. EXPERIMENTAL MATERIAL: 138 segments of coronary arteries were obtained from 21 patients aged 2-66 years undergoing heart transplantation. MEASUREMENTS AND MAIN RESULTS: 5-HT produced only concentration dependent contractions of coronary artery segments. No evidence was obtained for 5-HT receptors mediating either endothelium dependent or endothelium independent vasorelaxation. In tissue from patients without ischaemic heart disease, 5-HT effects were mimicked by (+/-)-alpha-methyl-5-HT (alpha-me-5-HT), a selective agonist at 5-HT2 receptors. In addition, the selective 5-HT1-like receptor agonist GR43175 produced contractions which achieved 30% of the maximum response to 5-HT. Responses to alpha-me-5-HT were surmountably antagonised by the non-selective antagonist methiothepin (0.1 mumol.litre-1) as well as the 5-HT2 receptor antagonist ketanserin (0.1 mumol.litre-1). In contrast GR43175 effects were resistant to blockade by ketanserin, but remained sensitive to methiothepin. Responses to the two agonists were not antagonised by the 5-HT3 receptor antagonist MDL72222 (1.0 mumol.litre-1). Vessel segments from ischaemic heart disease patients also contracted to alpha-me-5-HT and GR43175. Diseased arteries contracted with a decrease in the maximal response induced by both alpha-me-5-HT and by 90 mM K+ depolarisation compared to "normal" vessels, but the effect of GR43175 was preserved in the diseased arteries. Vascular rings adjacent to an atheromatous lesion were more reactive to GR43175 than serial segments taken distal to the lesion. CONCLUSIONS: These results show that both 5-HT1-like and 5 HT2 receptors mediate contraction of human epicardial coronary arteries and indicate that effects mediated by 5-HT1-like receptors but not 5-HT2 receptors are preserved in patients with ischaemic heart disease. PMID- 2272072 TI - [Osteocalcin]. AB - Osteocalcin, non-collagenous vitamin K dependent bone protein is as a biochemical indicator of osteoblastic activity and metabolic turnover in bone, valuable in the diagnosis of several diseases and in investigations of the dynamics of osseous changes (processes) during treatment of osteopathies. Elevated osteocalcin levels are normal in childhood and adolescence. In the diurnal rhythm the peak is recorded in the early hours. Pathologically elevated values are associated with primary hyperparathyroidism, Paget's disease, chronic renal failure, acromegaly and some malignities. A rise in women during the early postmenopausal period signalizes an enhanced metabolic turnover of bone in those women who are candidates of postmenopausal osteoporosis. Low levels are as a rule recorded in advanced age, in nanism, hypoparathyroidism, type 1 diabetes, rheumatoid arthritis, vitamin D deficiency, vitamin K deficiency, hypercorticalism and glucocorticoid treatment. PMID- 2272073 TI - [Hormones in bone metabolism. I. Calcitropic hormones]. AB - The review concentrates on calcitropic hormones (parathormone, calcitonin and the active metabolite of vitamin D-1,25-dihydroxyvitamin D3) and their action on bone remodeling. Attention is drawn to mechanisms of their action on the bone cell, on their manifestations in histology of osseous tissue and clinical symptomatology in pathological conditions. Attention is also drawn to the possible therapeutic application of calcitropic hormones. PMID- 2272074 TI - [Hormones in bone metabolism. II. Other systemic hormones]. AB - The authors present a review on a number of systemic hormones involved in bone metabolism. At the same time they demonstrate mechanisms of their action on the cellular, tissue and skeletal level. Attention is drawn to the participation of these hormones in the pathology of bone and other organs and the necessity to protect the skeleton during their therapeutic use in other than osteologic indications. PMID- 2272075 TI - [Levels of soluble receptors for interleukin-2 in the serum of patients with rheumatoid arthritis]. AB - The authors assessed, using the method of sandwich enzyme immunoassay (ELISA), the soluble receptor for interleukin-2 (s-r IL-2). In patients with rheumatoid arthritis mean values of 620.5 = 500.0 u./ml were recorded which was significantly higher than in patients with osteoarthritis (p less than 0.001) (313.3 +/- 155 n./ml) and in healthy controls (181.7 +/- 159.6 n./ml). In patients with rheumatoid arthritis a correlation was found between the activity of the disease expressed by means of Lansbury's index (r = 0.61, p less than 0.01). There was no correlation between s-r IL-2 and the sedimentation rate (r = 0.32, p = n. s.). The author reviews the literature and discusses the hypothesis that s-r IL-2 acts as a competitive inhibitor for interleukin-2. PMID- 2272076 TI - [Diagnosis of pulmonary embolism and monitoring of post-embolic changes in the vessels using pulmonary digital subtraction angiography]. AB - The group comprises 48 patients where digital subtraction angiography revealed embolization of the lungs. Forty-four of the patients were examined on account of clinical suspicion of embolism of the lungs, in the remaining four the examination was made on account of other indications. In four instances of 48 patients where we diagnosed or suspected embolism of the lungs DSA was also used to follow up the effect of heparinization and anti-aggregation therapy in relatively extensive findings revealed during the first examination. Based on their experience, the authors summarize angiographic pictures into four morphological types: perfusion defect, localized thinning and reduction of peripheral arterioles, sudden discontinuation of lobar and segmental arteries ("cut-off") and intraluminal defects in the contrast filling of arteries. The authors evaluate objectively the advantages and disadvantages of DSA and compare in the discussion the course of the examination, as well as the results with classical angiography, with perfusion and ventilation scan and try to find the correct place in the algorithm of visualization methods when embolism of the lungs is suspected. Based on the assembled experience, DSA of the lungs can be used as the first diagnostic method or after screening perfusion scan, if the latter is available immediately after development of complaints, as the second method. The authors analyze also the reasons of the relatively less frequent and very often late indication of this examination in this country. PMID- 2272077 TI - [Cardiac asthma after nifedipine and diltiazem]. AB - The authors describe the case of a 57-year-old male patient with severe left ventricular dysfunction (ejection fraction of left ventricle--37%, left ventricular end diastolic pressure 32 mm Hg) as a result of an extensive anterior Q infarction of the heart muscle. The patient did not have signs of congestive heart failure. He was treated on account of angina pectoris on exertion, grade III according to NYHA, hypertension and diabetes. Nifedipine and diltiazem administration led to repeated attacks of cardiac asthma. Calcium channel blockers should be administered to patients with angina pectoris and severe left ventricular dysfunction only when nitrates alone do not eliminate ischaemia and pain. They should be administered carefully and with the knowledge that they may in rare instances cause clinical deterioration of left ventricular function. PMID- 2272078 TI - [Physician-martyrs of the Czech resistance during World War II. VII]. PMID- 2272079 TI - [Health care and the Church]. PMID- 2272080 TI - Cytosolic free calcium concentrations in avian growth plate chondrocytes. AB - Isolated avian growth plate chondrocytes convert the acetoxymethyl ester (AM) form of Fura-2 quickly and efficiently to the Ca2(+)-sensitive pentacarboxylic acid (FA) form. Control experiments indicate that the Kd for intracellular Fura 2/FA is very close to that of extracellular Fura-2/FA at the same ionic strength and pH and that the Fura-2/FA fluorescence from indicator converted by intracellular organelles is quite small. Correcting for the effects of extracellular Fura-2/FA and partial hydrolysis products has improved the accuracy of determination of intracellular [Ca2+] over earlier measurements in chondrocytes. Cytosolic [Ca2+] in isolated growth plate chondrocytes (containing cells from each maturational stage) is found to require approximately 9 hours to recover from the isolation process. After this recovery period, cytosolic [Ca2+] in these cells converges to approximately 70 nM regardless of the [Ca2+] of the recovery medium, suggesting regulation of cytosolic [Ca2+] to a set point. Chondrocytes that are separated into maturationally distinct fractions using countercurrent centrifugal elutriation show an increase in cytosolic [Ca2+] with cellular maturation. The least mature resting cells have a [Ca2+] near 57 nM, while the most mature hypertrophic cells are around 95 nM. PMID- 2272081 TI - Sphingosine increases inositol trisphosphate in rat parotid acinar cells by a mechanism that is independent of protein kinase C but dependent on extracellular calcium. AB - In rat parotid acinar cells prelabelled with [3H]-inositol, sphingosine stimulated the accumulation of [3H]-inositol polyphosphates. When the cells were exposed to sphingosine, [3H]-inositol trisphosphate (InsP3) was accumulated in a time- and dose-dependent manner. When the extracellular Ca2+ was chelated by 1 mM EGTA, the effect of sphingosine on InsP3 accumulation was completely inhibited. Ionophores, A23187 and ionomycin, had no significant effect on InsP3 accumulation. An inhibitor of protein kinase C, 1-(5-isoquinolinesulfonyl)-2 methylpiperazine (H-7), failed to stimulate InsP3 accumulation. In the homogenate of parotid acinar cells, InsP3 3-kinase and 5-phosphomonoesterase activities were not affected by sphingosine. These results suggest that sphingosine activates phosphoinositide turnover by a mechanism dependent upon extracellular Ca2+, but different from that of an ionophore, and independent of protein kinase C. PMID- 2272082 TI - Intracellular Ca2+ measurement with Indo-1 in substrate-attached cells: advantages and special considerations. AB - The dual emission, Ca2+ sensitive fluorescent dye, Indo-1, offers several potential advantages over its dual excitation analogue, Fura-2. Most notable among these advantages are increased speed of measurement using dual wavelength photometry and the absence of a requirement for special quartz optics. Despite these potential advantages, only a tiny fraction of the microscopic studies of intracellular free calcium ([Ca2+]i) on substrate-attached cells has employed Indo-1. Among the reasons for the infrequent use of Indo-1 are the fact that it exhibits somewhat different spectral properties in the cytosol than it does in extracellular buffers, and the notion that it is much more sensitive to photobleaching than Fura-2. We report here that under our experimental conditions, Indo-1 photobleaching is small and does not noticeably affect the measurement of free Ca2+, even after 30 minutes of continuous illumination. We also report a new method for creating in situ standard curves that is easy, reproducible, and yields values for [Ca2+]i that are identical to those obtained with Fura-2. In addition, we have found that Indo-1 is less subject than Fura-2 to compartmentalization within subcellular organelles. These results provide baseline data to take advantage of the significant improvement afforded by Indo-1 in the measurement of rapid [Ca2+]i responses and the avoidance of compartmentalization artifacts during experiments of long duration. PMID- 2272084 TI - Fourniers gangrene in Nigerians: presentation and management. PMID- 2272083 TI - Primary carcinoma of gallbladder in Tanzania. A twenty-year review. AB - This study comprises a review of all patients of primary carcinoma of gallbladder based on biopsy material received from 1969-1988 at the Cancer Registry of the Central Pathology Laboratory, Muhimbili Medical Centre, Dar es Salaam. This study is the first of its kind involving primary carcinoma of gallbladder in Tanzania. The clinical and pathological features of ten patients of primary carcinoma of gallbladder treated at Muhimbili Medical Centre are described. Males outnumbered females. The maximum incidence was seen in the 6th decade. Pain and the presence of a mass were two most common clinical features. Gallstones coexisted in 40 percent of patients. Ancillary investigations were of little value in preoperative diagnosis. At laparotomy cholecystectomy was possible in all the cases owing to inapparent carcinoma of gallbladder. One patient is alive 6 months after surgery. PMID- 2272085 TI - Iron stores of Nigerian blood donors as assessed by serum ferritin concentration. AB - Haematological indices and parameters of iron status were obtained from 29 normal male subjects and from 32 male blood donors. Percentage saturation of transferrin with iron and the usual erythrocyte parameters of iron status were similar in both group of subjects. The mean ferritin concentration was 64.75 ng/ml +/- 4.6 (SEM) in normal males and 49.19 ng/ml +/- 5.1 (SEM) in the male donors. This difference was statistically significant (p less than .05). Serum ferritin concentration thus appears to be a sensitive index of iron stores. The results also indicate that some blood donors may be pre-latent or latent iron deficient at the time of donation and may manifest as iron deficient after blood donation. Based on these findings, it is suggested that blood donors be given iron supplementation and those who do not meet the minimum screening haemoglobin concentration be further investigated and treated. PMID- 2272086 TI - Antimicrobial susceptibility pattern of Aeromonas and Plesiomonas strains isolated from patients with diarrhoea in Nigeria. AB - The susceptibilities of 53 isolates of Aeromonas species and 16 Plesiomonas shigelloides, from patients with diarrhoea, to 15 commonly used antimicrobial agents were determined by the disk-agar diffusion technique. All the strains were susceptible to ofloxacin, a recent quinolone. Also, over 70 pc of our strains were susceptible to gentamicin, carbenicillin, ceftriaxone, erythromycin, Chloramphenicol, tetracycline and co-trimoxazole. However, less than 30 pc of our strains were susceptible to ampicillin. Results of this in vitro study indicate that for cases of serious Aeromonas or Plesiomonas infections requiring antimicrobial therapy, ofloxacin, gentamicin, carbenicillin or chloramphenicol could be useful. PMID- 2272088 TI - Iodine deficiency disorders--what importance to Zimbabwe? PMID- 2272087 TI - Hypertension control in Harare municipal clinics. AB - Treatment of hypertension is a growing burden on urban health services in Zimbabwe. In 1980, the Harare Health Department began a separate registry, staffed by a nurse, for management of patients with stable hypertension (diastolic blood pressure (DBP less than 100 mmHg) on treatment). We evaluated this programme in a retrospective review of 437 medical records. The average age of patients was 17.5 years; two-thirds were women. Upon referral 324 patients (74 percent) had a DBP less than mmHg. Sixty-five percent of patients had no DBP greater than 100 mmHg during follow-up. Patients with DBP greater than 20 mmHg were more likely to be treated with two drugs, seen more often or referred (p less than 05). One-third of patients enrolled between 1980-1986 were lost to follow-up. Of those who did not default, few attended regularly. We conclude that a nurse can successfully manage patients with stable hypertension, although more aggressive treatment and improved compliance would have resulted in better control. At current levels of loss to follow-up, this programme is unlikely to have much effect on the public health impact of hypertension. The main challenge is to improve patient compliance. PMID- 2272089 TI - AIDS and workplace. PMID- 2272090 TI - Migraine, serum serotonin and platelet 5-HT2 receptors. AB - In spite of recent theories about the aetiopathogenesis of migraine, serotonin continues to play a central role, explaining the efficacy of almost all migraine prophylactic drugs. In migraineurs with and without aura we measured (by HPLC-EC) the serum serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels between as well as during headache attacks. Between attacks of migraine with aura and at the beginning of attacks of both types of migraine the serum 5-HT and 5-HIAA concentration was significantly increased. These results were corroborated by 3H spiperone binding to platelet membranes: in migraineurs with aura in the attack free interval, there was a significant decrease in its Bmax, which suggests down regulation of 5-HT2 receptors. In conclusion, we have verified that migraine with aura differs biochemically from migraine without aura. PMID- 2272091 TI - Cluster headache: ultrastructural evidence for mast cell degranulation and interaction with nerve fibres in the human temporal artery. AB - It has been suggested that histamine plays an important role in the pathogenesis of cluster headache. In addition, both neurogenic and vascular components have been described during cluster headache attacks without an obvious anatomical link between them. Our ultrastructural observations of human temporal arteries from cluster headache patients and their comparison to those from a control group strongly suggest that mast cells may be this link. Mast cells in both groups show a very close apposition with nerve fibres, suggesting a functional interaction between them. Moreover, in the cluster headache group exclusively, adventitial mast cells show profound morphological modifications suggesting progressive degranulation. These data strongly suggest that mast cells could be directly or indirectly involved in the pathophysiology of cluster headaches. PMID- 2272092 TI - Propranolol in acute migraine: a controlled study. AB - Propranolol is an established agent in migraine prophylaxis. Uncontrolled studies have suggested an action in the acute attack. We present the first double-blind placebo controlled study of propranolol in 27 unselected patients with common (migraine without aura) and classical (migraine with aura) migraine. There were 23 pairs of headaches in the 14 patients who completed the study. No difference was found, when the data were analysed by headache pair or by patient, in severity duration and subjective assessment of efficacy between those treated in an attack with propranolol 40 mg and placebo. PMID- 2272093 TI - Neuroendocrine dysfunction in cluster headache. AB - Current views on cluster headache pathogenesis indicate a primary central nervous system dysfunction, in particular a hypothalamic involvement. To confirm the hypothalamic involvement in cluster headache we evaluated the hypothalamic pituitary axis responsiveness with the thyrotrophin releasing hormone (TRH) test. A dose of 200 micrograms of TRH was administered i.v. to nine healthy controls, 32 patients with cluster headache during cluster period and 16 in remission period. Delta maximum thyrotrophin (TSH) was significantly lower in patients with cluster headache during cluster period (p less than 0.05 versus healthy controls and cluster headache patients in remission). No difference was observed between healthy controls and cluster headache patients in remission. A monoaminergic dysfunction at the hypothalamic level is hypothesized. PMID- 2272094 TI - An open study comparing manual therapy with the use of cold packs in the treatment of post-traumatic headache. AB - One year after head trauma, 23 patients with post-traumatic headache entered a prospective clinical controlled trial to find out if specific manual therapy on the neck could reduce the headache. The study was completed by 19 patients (83%). Ten patients were treated twice with manual therapy and nine patients were treated twice with cold packs on the neck. The pain index was calculated blindly. Two weeks after the last treatment the mean pain index was significantly reduced to 43% in the group treated with manual therapy compared with the pretreatment level. At follow-up five weeks later, the pain index was still lower in this group compared with the group treated with cold packs, but this difference was not statistically significant. The pain index for all 19 patients was significantly correlated to the use of analgesics as well as to the frequency of associated symptoms (number of days per week with dizziness, visual disturbances and ear symptoms). It is concluded that the type of manual therapy used in this study seems to have a specific effect in reducing post-traumatic headache. The result supports the hypothesis of a cervical mechanism causing post-traumatic headache and suggests that post-traumatic dizziness, visual disturbances and ear symptoms could be part of a cervical syndrome. PMID- 2272095 TI - Increase in plasma methionine-enkephalin levels during the pain attack in episodic cluster headache. AB - Since high levels of endogenous opioids (endorphins, enkephalins) were found in brain areas classically related to nociception, their peripheral levels in humans were studied in different pain syndromes yielding contradictory results. This study was undertaken to assess changes in plasma methionine-enkephalin (met enkephalin) levels in patients with episodic cluster headache associated with the pain period. Twenty-nine patients, 24 in the cluster period (6 of them during an attack) and 3 in the remission period were studied. Two other patients were subjected to a longitudinal follow-up. Plasma met-enkephalin levels were determined by radioimmunoassay (RIA) with specific antibody. Plasma peptide concentration (pmol/ml) was higher (p less than 0.001) in patients during the pain attack (3.97 +/- 1.18) than in controls (0.25 +/- 0.03). When measured 4 and 48 h after the pain attack lower levels were found (0.46 +/- 0.06) which decreased to control values after 24 h. These results may suggest involvement of peripheral enkephalins in pain modulation in patients with episodic cluster headache. PMID- 2272096 TI - Contralateral trigeminal dysaesthesias associated with second cervical nerve compression: a case report. AB - This 70-year-old woman presented with a left C2 solitary metastatic lesion producing ipsilateral occipital pain associated with contralateral fronto-orbital dysaesthesias. Examination revealed analgesia in the left C2 dermatome and hyperaesthesia in the right forehead. These symptoms and findings resolved following a course of radiation therapy to the C2 metastasis. Ipsilateral trigeminal dysaesthesias produced by cervical lesions have been described, however, contralateral cervicogenic trigeminal dysaesthesias have not. Relevant experimental data are analysed; neural pathways are suggested by which a cervical lesion, especially at C2 or C3, may produce trigeminal dysaesthesias referred ipsilaterally or contralaterally. PMID- 2272097 TI - Complicated migraine studied by phosphorus magnetic resonance spectroscopy. AB - The brain and skeletal muscle of eight adult patients with migraine with prolonged auras or migraine strokes leaving a permanent hemianopic defect were studied by phosphorus magnetic resonance spectroscopy. Biochemical assays performed on muscle biopsy and platelets had revealed abnormal mitochondrial enzyme activities. Brain magnetic resonance spectroscopy showed an abnormally low phosphocreatine to inorganic phosphate ratio in all patients, apparently due to decreased phosphocreatine and increased inorganic phosphate contents. Muscle phosphorus magnetic resonance spectroscopy showed low recovery from exercise in seven patients. Three patients had an increased phosphocreatine/inorganic phosphate ratio at rest, and the exercise transfer characteristics were abnormal in four patients for relatively low levels of exercise. The mitochondrial metabolic defects present in platelets and muscle of complicated migraine patients are therefore also expressed in the brain. PMID- 2272098 TI - Drug delivery systems for antitumor activation of macrophages. AB - Macrophages, one of the immunologically competent cells centrally contributing to host defense mechanisms, can be stimulated by a variety of immunomodulatory agents to exert antitumor activity. However, many problems, such as serious side effects attributed to the high-dosage regimens of the drugs, should be addressed for successful tumor immunotherapy using immunomodulatory agents. Thus, it is essential to develop carrier systems that use much lower doses of the drugs. This article reviews the carrier systems of drugs for effective immunopotentiation, especially macrophage activation of antitumor function. Since research in this field has just started, few investigations, including ours, have been reported. PMID- 2272100 TI - LDL-mediated drug targeting. AB - The possibilities and limitations in using the low-density lipoprotein (LDL) as a carrier for drugs are discussed. LDL, which may be regarded as the natural counterpart of liposomes, possesses a lipid core that may be utilized as a drug reservoir. Unlike most types of liposomes, the endogenous LDL particle is not avidly taken up by the reticuloendothelial system and may persist in the circulation for prolonged times after injection. A well-characterized membrane receptor recognizes LDL, and binding appears to be coupled to uptake and intracellular processing. Since many tumor tissues express a high amount of LDL receptors, there is a rationale for the design of a toxic LDL-cytostatic drug complex. The behavior of LDL in vivo will be discussed and the principles of LDL mediated targeting to tumor cells will be evaluated. In addition, methods for drug incorporation into LDL will be critically assessed, while evaluation methods will be presented that may set the standards for future research. PMID- 2272099 TI - Transdermal delivery of contraceptives. AB - Contraceptive agents are administered to the body through a variety of routes. Research has recently been directed at examining the transdermal route for systemic delivery of contraceptive agents, including estrogens and progestins. The transdermal route has several potential advantages over the other routes of administration: (1) improved compliance, (2) once-weekly administration, (3) delivery is easily terminated, and (4) some side effects can be alleviated based on more constant delivery rates. This article reviews the permeability of skin toward contraceptive steroids and how skin permeability is evaluated. The metabolism of contraceptive steroids is also considered. Transdermal delivery systems used to deliver contraceptives are presented, followed by a detailed discussion of several delivery systems for specific contraceptive agents such as levonorgestrel and estradiol. The potential problem of skin irritation is presented as it relates to transdermal contraceptive delivery systems, all of which will be worn chronically. PMID- 2272101 TI - [The role of the kidney and liver in the total metabolism of (125I) ortho iodobenzoate in rats]. AB - The contribution of the kidney and liver to the total metabolism of (125I)ortho iodobenzoate (OIB) was studied in rats with the aim considering the suitability of the use of this radiopharmaceutical as a diagnostic agent of the conjugation function of the liver. For the analysis of OIB metabolism (formation of conjugates with glycine and glucuronic acid) in rats, the techniques of the perfused rat kidney "in situ" and the isolated perfused rat livers were used. A comparison of the relative representation of OIB metabolites in the urine of intact rats with the results obtained in the urine from the perfused kidney and the perfusion fluid from the isolated perfused liver gives evidence of preferential biotransformation of OIB in the kidney. As shown in a biodistributional study of OIB in rats, OIB concentration in the renal tissue and thus the supply for the metabolic processes in the kidney is higher by orders than it is in the liver tissue, which could explain the above-mentioned finding. Assuming that the biotransformational organ capacity for this drug in man is similar to that in the experimental rat, the use of OIB for quantification of the detoxicating function of the liver in man is debatable. PMID- 2272102 TI - [The role of calcium ions in the contractility of cardiac muscles and possible effects of various substances]. PMID- 2272103 TI - Shigellosis in New Brunswick. PMID- 2272104 TI - Community outbreaks of shigellosis--United States. PMID- 2272105 TI - Influenza in Canada, 1989-1990 season. PMID- 2272106 TI - A procedure for identifying influenza epidemics. PMID- 2272107 TI - Influenza virus strain identification for the 1989-1990 season. PMID- 2272108 TI - Influenza serosurvey for the 1990-1991 season. Prevalence of antibody to current influenza virus strains in a 1990 Canadian serosurvey [corrected]. PMID- 2272109 TI - Influenza surveillance. PMID- 2272110 TI - [Need for head nurses to know management techniques]. PMID- 2272111 TI - [Nursing care of percutaneous transluminal coronary laser angioplasty]. PMID- 2272112 TI - [Experience in nursing of patients with massive bleeding over 4000 ml in viscus rupture (with 13 case reports)]. PMID- 2272113 TI - [Nursing care of rectal cancer operated on with pull through procedure]. PMID- 2272114 TI - [Comparison of shaving or not shaving in skin preparation for gynecological abdominal surgery]. PMID- 2272115 TI - [Breast massage to promote milk secretion for pregnant and parturient women]. PMID- 2272116 TI - Effects of inositol 1,4,5-trisphosphate on calcium release from the endoplasmic reticulum and Golgi apparatus in mouse mammary epithelial cells: a comparison during pregnancy and lactation. AB - It has been established that inositol 1,4,5-trisphosphate(IP3) is responsible for the mobilization of calcium(Ca2+) from intracellular locations in a wide variety of tissues, and that this response triggers the stimulation of several hormones and neurotransmitters. However, these phenomena have yet to be examined in the mammary epithelium. Ca2+ uptake from the medium into the endoplasmic reticulum(ER) and Golgi apparatus in vitro in both pregnant and lactating mouse mammary epithelial cells was studied and a strong Ca2+ release from these organelles into the medium with the use of IP3 was shown. The Ca2+ uptake and its release due to IP3 was also usually greater during pregnancy than lactation. PMID- 2272117 TI - Methotrexate: studies on cellular metabolism. IV. Effect on the mitochondrial oxidation of cytosolic-reducing equivalents in HeLa cells. AB - The effect of methotrexate (MTX) on the mitochondrial oxidation of cytosolic reducing equivalents in HeLa cells was studied. MTX inhibited (100 per cent) malate dehydrogenase activity, but no effect was observed on that of GOT. MTX (0.5 mM) inhibited (100 per cent) the activity of reconstituted enzymatic system MDH-GOT, probably as a consequence of inhibition of malate dehydrogenase activity. MTX decreased pyruvate production (54 per cent), demonstrating its inhibitory action on the malate-aspartate shuttle. Blockage of the malate aspartate shuttle by MTX accounts for the decrease in cellular energetic gain. The results obtained are consistent with the view that in HeLa cells, as well as in other tumour cells, the transport of reducing equivalents from cytoplasmic NADH into the respiratory chain of mitochondria is via the malate-aspartate shuttle. PMID- 2272118 TI - Impairment of ATP-linked reactions in mitochondria isolated from skeletal muscle of halothane-sensitive pigs. AB - Oxygen consumption was depressed in mitochondria isolated from halothane sensitive pig (HP) muscle. The calculation of the respiratory control ratio (RCR) indicated that mitochondria were more affected at the site-I level of the respiratory chain. Calcium accumulation in these mitochondria was not altered when driven by the oxidation of succinate. This process was abolished when linked to ATP as a source of energy. ATP transport was completely inhibited in (HP) mitochondria. PMID- 2272119 TI - Modulation of membrane phenotype, matrix adhesion and microinvasiveness of metastatic tumour cells by HUdR. AB - The effect of HUdR, proved to be anti-metastatic in vivo, was studied in vitro on cell proliferation, nucleoside uptake, membrane fluidity, expression of galactosylated glycans and proteoglycans in metastatic HM tumour cells. The observed increase in membrane fluidity and the suppression of nucleoside transport were early events of the HUdR action followed by decrease of galactosylated glycan and HSPG expression. However, these changes did not influence the proliferation capacity of the cells at the concentrations studied. As a consequence of the membrane alterations a reduced adhesiveness and spreading on extracellular matrix components was detected. In addition, the HUdR treated HM cells showed reduced capacity to invade fibroblast monolayers in vitro. Based on these observations, HUdR could be the prototype of new anti-metastatic agents acting at the level of tumour-host interaction. PMID- 2272120 TI - Amelioration by menadione of the experimental chronic immune arthritis in the rabbit. AB - The immunological induction of arthritis in the knee of the rabbit is well established as a model for human rheumatoid arthritis. It has the special advantage of allowing the development of the condition, and the effect of disease modifying agents, to be followed. Attention has been focussed on the activity of glucose 6-phosphate dehydrogenase in the synovial lining cells since the fourfold elevation of this activity was shown to be fundamental in the human condition. An equal elevation of this activity has now been demonstrated in the rabbit model. Furthermore, it has been shown that the oral administration of menadione decreases this activity towards normality with a concomitant decrease in the degree of inflammation. PMID- 2272121 TI - Yersinia enterocolitica: intestinal features. PMID- 2272122 TI - Helicobacter pylori: its role in gastric disease. PMID- 2272123 TI - Bacterial short chain fatty acids: their role in gastrointestinal disease. PMID- 2272124 TI - Twenty-four-hour intragastric acidity. An update. PMID- 2272125 TI - Philosophers and stones in acute pancreatitis. PMID- 2272126 TI - Vasodilatory effects of milrinone on pulmonary vasculature in dogs with pulmonary hypertension due to pulmonary embolism: a comparison with those of dopamine and dobutamine. AB - 1. The limited therapeutic role of pulmonary vasodilation reflects lack of their selectivity for the pulmonary vasculature, and many drugs have been evaluated for effectiveness; however, none has gained widespread clinical use. 2. Milrinone (MIL) is a newly synthetized phosphodiesterase inhibitor, which has potent positive inotropic and vasodilatory effects. 3. The present study shows the effects of MIL on the pulmonary circulation in dogs with pulmonary hypertension due to autologous muscle-induced pulmonary embolism, and also demonstrates a comparison with those of dopamine and dobutamine. 4. As MIL showed potent vasodilatory effects on the pulmonary vasculature, it had a potential clinical role in the treatment of pulmonary hypertension. PMID- 2272127 TI - Systemic and regional effects of endothelin in rabbits: effects of endothelin antibody. AB - 1. The effects of porcine endothelin-1 (10(-12)-5 x 10(-10) mol/kg) on arterial blood pressure (BP) and the renal, mesenteric and carotid blood flow (BF), and the effects of endothelin-1 antibody were studied in rabbits. 2. Endothelin-1 caused a sustained increase in BP. The renal, mesenteric and carotid BF were decreased dose-dependently by endothelin-1. The approximate half-maximal effective values (ED50) were 5.5 x 10(-11), 8.6 x 10(-11) and 2.0 x 10(-10) mol/kg for renal, mesenteric and carotid BF respectively. Compared with carotid BF, the renal and mesenteric BF responses were significantly more sensitive to endothelin-1. 3. Combined administration of endothelin-1 and its antibody showed a significant inhibition of the BP and renal BF responses. However, endothelin-1 antibody alone did not change either BP, renal BF, mesenteric BF or carotid BF in vivo. 4. The present results demonstrate that endothelin is a potent vasoconstrictor in vivo. However, circulating endothelin may not contribute to the control of BF and BP. The role of endothelin as a local modulator of the vascular tone remains to be investigated. PMID- 2272128 TI - Effect of lignocaine on coronary blood flow, systolic myocardial function and myocardial high energy phosphate stores in swine. AB - 1. To investigate the effect of lignocaine upon coronary blood flow, myocardial systolic wall function and high energy phosphate stores, lignocaine was administered as a rapid intravenous injection to 14 open chest anaesthetized swine. 2. Before and after injection, measurements were made of coronary blood flow by electromagnetic flow probe, per cent wall thickening by ultrasonic crystals, adenosine triphosphate (ATP) and creatine phosphate (CP) content by myocardial biopsy, and arterial pressure by central aortic catheter. The animals were divided into two groups based on whether or not they received a continuous low-dose infusion of lignocaine prior to the study. Group I received the continuous low-dose infusion of lignocaine and group II did not. 3. With a 2 mg/kg lignocaine injection, peak diastolic coronary flow rose significantly in groups I and II by 27 +/- 7 and 29 +/- 7% respectively. This was followed by a significant decline in per cent wall thickening in groups I and II of -11 +/- 2 and -19 +/- 6% respectively. In group I myocardial CP content decreased after lignocaine injection by 58 +/- 6% and ATP tended to rise even though systolic and diastolic pressure did not change significantly. In group II neither CP nor ATP changed significantly, but systolic and diastolic blood pressure decreased significantly. 4. Repeat lignocaine injections were given over a wider dosage range (0.5-4.0 mg/kg) to determine dose-response for lignocaine versus coronary blood flow. Coronary blood flow increased and per cent wall thickening decreased as doses of lignocaine were increased. 5. It was concluded that rapid intravenous lignocaine injection appeared to cause a dose-dependent coronary dilatation and systolic dysfunction. Pre-treatment with low-dose continuous infusion of lignocaine appeared to result in a decrease in CP and a rise in ATP when compared with no pre-treatment--despite a similar effect on myocardial function and coronary blood flow. PMID- 2272129 TI - Body growth and polycythaemia in hypoxic albino rats of first and second generation. AB - 1. In our study we followed the growth rate and the haematologic changes occurring in albino rats of Wistar strain when living in a hypoxic environment. Two generations of hypoxic rats were observed for changes in their erythrocytes (RBC), haematocrit (Hct) and haemoglobin (Hb): the first generation (H1) and the second generation (H2). A few hours after birth, the H1 rats were placed and raised in a normobaric hypoxic environment (10% O2 in N2). The H2 rats were born and raised in the environment previously described. The control group had a normoxic environment. The H1 and H2 rats had inferior growth rates in respect to their controls, but H2 were found to have a larger growth rate than the H1 group. The RBC, Hct and Hb had values significantly greater for both H1 and H2 when compared with their controls. However, we did find that the values of H2 were significantly lower than H1. We believe that these results are in relation to the degree of development of the adaptive processes to the hypoxic environment of the H2 rats. PMID- 2272131 TI - Clinical cardiology and molecular biology. PMID- 2272130 TI - The effect of ivermectin on some haematological indices in rabbits: influence of vitamin K treatment. AB - 1. Rabbits were treated with the antiparasitic drug ivermectin at subcutaneous doses of 0.2, 1 and 2.5 mg/kg and blood collected weekly for 4 weeks thereafter for measuring some blood parameters. At a dose of 0.2 or 1 mg/kg the drug had no significant effect on any of the parameters measured. At a dose of 2.5 mg/kg, the drug reduced significantly the erythrocyte counts, haemoglobin concentration, haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular haemoglobin on weeks 1, 2, 3 and 4. Platelet counts were not significantly affected. 2. In another trial, ivermectin was injected subcutaneously at a dose of 2.5 mg/kg, after pre-treatment with either saline or vitamin K (30 micrograms/kg for 30 days), and prothrombin time, bleeding time and platelet counts measured at weekly intervals for 4 weeks. Bleeding time and thrombin time were significantly increased 1 week after treatment, and remained higher than the control for 4 weeks. PMID- 2272132 TI - Managing the pregnant patient with heart disease. AB - Pregnancy and its associated hemodynamic challenge presents potential risks to the patient with cardiac disease, whether acquired or congenital. The hematologic changes which occur during pregnancy include alterations in blood volume, hematocrit, and blood viscosity. There are also alterations in cardiac output and regional blood flow patterns. These hemodynamic alterations are associated with signs and symptoms which can be impressive yet benign, or can suggest poor outcome, depending on the underlying cardiovascular disorder. The clinician is faced with the sometimes difficult task of differentiating the benign from the dangerous while making appropriate management decisions. In this article, diagnosis and current management of many of the more common acquired and congenital cardiac abnormalities are discussed as they pertain to the gravid female. The effects of common cardiovascular medications in pregnancy are also briefly reviewed. PMID- 2272133 TI - Clinical characteristics affecting success or failure of PTCA in patients with multiple vessel disease and poor candidates for surgery. AB - A special form of complex coronary angioplasty is represented by the extension of indications for percutaneous transluminal coronary angioplasty (PTCA) to patients with multivessel disease (MVD) for whom surgery is not indicated, and thus for whom surgical standby is not available. Over a two-year period, 254 consecutive coronary patients with multivessel disease underwent PTCA under such conditions. These patients could not benefit from surgery for various reasons. Of the 612 arteries involved, 155 were occluded, 47 had been previously bypassed. A distal nonbypassable lesion in one of the three major arteries was found in 244 patients, 61 had suffered from a previous infarct, 24 demonstrated an ejection fraction below 0.40, and in 19 a single patent vessel was found. Fifteen patients were in cardiogenic shock and 69 procedures were undertaken for unstable angina. Of this latter group, 25 emergency PTCA were attempted for refractory unstable angina, and 44 additional emergency procedures were directed to the treatment of acute infarct. A total of 40 intra-aortic counterpulsations were needed. As far as possible the procedure aimed at full revascularization. Immediate outcome is strongly affected by the clinical context, and despite a rather constant initial success rate (88-95%), the procedural mortality (directly related or not) can change dramatically with clinical factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272134 TI - Differentiation between left circumflex and right coronary artery occlusions: studies on ST-segment deviation during percutaneous transluminal coronary angioplasty. AB - To distinguish between acute occlusion of the right coronary artery (RCA) and the left circumflex artery (LCx) by electrocardiography, we studied ST-segment deviation during balloon inflation in percutaneous transluminal angioplasty. The composite electrocardiographic criteria based on ST-segment deviations increased the diagnostic specificity: that is, the finding of inferior infarction (ST segment elevation in leads II, III, aVF) without lateral infarction (ST-segment elevation in leads V5,6) was highly suggestive of RCA occlusion (sensitivity and specificity: 35 of 43 cases, 81.4%; and 33 of 36 cases, 91.7%), whereas ST segment elevation in leads V5,6 (LCx: 23 of 36 cases; 63.9%, RCA: 5 of 43 cases; 11.6%) or isolated ST-segment depression in leads V2-4 (LCx: 9 of 36 cases; 25.0%, RCA: none of 43 cases) was highly suggestive of LCx occlusion. These results indicate that the composite electrocardiographic criteria were useful in predicting the artery involved in acute myocardial infarction, although any single criterion was not sensitive or specific enough to differentiate right from left circumflex coronary artery occlusion. PMID- 2272135 TI - Acute anterior myocardial infarction: streptokinase prevents ventricular thrombosis independently of its effect on infarct size. AB - Left ventricular thrombosis (LVT) is a frequent complication after acute anterior myocardial infarction (AMI). The purpose of this study is to evaluate whether streptokinase (SK) therapy prevents LVT, and whether this effect is due to the preservation of left ventricular function or to the fibrinolytic action of the drug. Sixty-five patients who underwent a left ventricular angiography within 2 months after a first AMI were studied. Twenty-eight patients (SK group) received SK 1,500,000 U i.v. administered over 60 min within 6 h from the onset of symptoms. A lower incidence of LVT was found in the SK group (p = 0.0003). We divided patients into two classes according to the value of akinetic-dyskinetic area (AD): the first group with a lower value of AD, the second group with a higher value of AD. In both groups, a reduced incidence of LVT was associated with SK therapy (p = 0.014, p = 0.015, respectively). Early infusion of SK during AMI seems to prevent the development of LVT, with an effect partly independent from its action on infarct size for small to large myocardial infarction. PMID- 2272136 TI - A comparison of heparinized low osmolality ionic and nonionic contrast media in 500 patients undergoing cardiac angiography. AB - Low osmolar contrast media (CM) cause less hemodynamic and electrical changes than conventional CM, and many cardiologist have switched to the newer agents. Recently, concerns about a possible increased frequency of thromboembolic complications with low osmolar CM have been raised. This study compared two low osmolar heparinized CM, one ionic (Hexabrix) and the other nonionic (Isovue), in 500 consecutive patients undergoing either diagnostic catheterization (417) or coronary angioplasty (83). Adverse effects were uncommon (37 patients), but were more frequent with Hexabrix (12%) than Isovue (3%); p less than 0.05. The most common adverse effects were nausea or vomiting. Death, related to abrupt occlusion of a severe left main stenosis occurred in one patient who received Hexabrix, and acute pulmonary edema occurred in one patient who received Isovue. No apparent thromboembolic complication occurred. In conclusion, both low osmolar CM were well tolerated, but Hexabrix caused more transient nausea or vomiting. Both CM were safe and the incidence of thromboembolic complications when prospectively looked for was very low. PMID- 2272137 TI - Ventricular tachycardia overdrive and entrainment with and without fusion: its relevance to the catheter ablation of ventricular tachycardia. PMID- 2272138 TI - Tomographic views of normal and abnormal hearts: the anatomic basis for various cardiac imaging techniques. Part I. AB - Recent developments have taken place in the diagnosis of cardiovascular disorders in the area of cardiac imaging techniques. From a previous era of imaging by silhouettes (chest roentgenography, fluoroscopy, angiocardiography), we have emerged into an era of imaging by tomographic scanning (echocardiography, radionuclide tomography, computed tomography, magnetic resonance). A basic understanding of tomographic cardiac anatomy is the foundation for proper use and interpretation of these new imaging modalities. The present report provides a description of the techniques of tomographic cutting of necropsy cardiac specimens and illustrates some of the pathologic cardiac abnormalities cut in these tomographic planes. Part I of this report describes position of the heart and tomographic axis planes, preparation of the heart and methods of cutting at necropsy, and the short-axis, two-chamber, and four-chamber views of the heart. PMID- 2272139 TI - Automatic junctional tachycardia in an adult. AB - We report an adult patient with junctional ectopic tachycardia, a condition which was initially described in infants, frequently in association with congenital defects. The patient had a rapid, irregular paroxysmal junctional tachycardia with a rate ranging from 160 to 220 beats/min, distinguishing it from the more common nonparoxysmal junctional tachycardia in which a slower heart rate is seen. The electrophysiological study performed during an episode of tachycardia demonstrated periods of atrioventricular dissociation and narrow QRS complexes as well as a junctional ectopic rhythm, which was suggested by a His deflection preceding each ventricular depolarization with a normal HV interval. Both the response to exercise and the results of atrial and ventricular stimulation suggested enhanced automaticity of a high junctional focus. Therapy combining procainamide, verapamil, and digitalis proved to be effective. Thus, junctional ectopic tachycardia can also occur in adults, probably due to enhancement of automaticity. PMID- 2272140 TI - Lazzaro Spallanzani. PMID- 2272142 TI - Human neurolymphomatosis in a patient with chronic lymphatic leukemia. AB - A 62-year-old woman with chronic lymphatic leukemia (CLL) (RAI stage IV) with multiple organ involvement and diabetes mellitus, three months prior to death presented with a symmetrical sensory neuropathy of the upper extremities with little motor impairment and, two months later, sensory atactic neuropathy of the lower limbs. No cranial nerve or CNS impairment was noted. Clinical diagnosis was predominantly sensory neuropathy, but nerve conduction velocities were normal on upper limbs and moderately abnormal on lower limbs, the latter attributing to long lasting diabetes mellitus. The women died from acute subarachnoid hemorrhage. Autopsy revealed CLL of B-cell type with generalized organ involvement and acute craniospinal subarachnoid hemorrhage from ruptured cerebral aneurysm. There was selective neoplastic infiltration of the dorsal root ganglia and peripheral nerves, particularly the median nerve. Although selective infiltration of peripheral nerves by B-cell lymphoma cells was not associated with myelo-axonal degeneration, the relationship of this case to human neurolymphomatosis is discussed. PMID- 2272141 TI - Primary cerebral lymphoma--a clinico-pathological study. AB - A series of 18 patients with primary cerebral lymphoma (PCL) is presented. The clinical, radiological and histological findings are shown along with the results of treatment. Patients were aged 21-76 years (mean 61 years) with a male predominance of 1.6:1. Computed tomography (CT) scans were performed on 15 patients. Typically lesions were multiple, isodense, and showed uniform enhancement with contrast medium. Immunocytochemical studies demonstrated 15 B cell and 3 T-cell lymphomas. The overall median survival from diagnosis was 3 months. Survival was improved with radiotherapy to 9 months. The difference in survival between those patients treated with surgery and steroids alone, and those who, in addition, received radiotherapy was statistically significant (p less than 0.05). We discuss the results of treatment of PCL in both this series and the literature. We also consider the increased incidence of PCL seen in this unit in 1987 and 1988 and the possible reasons for it. PMID- 2272143 TI - Topography of Alzheimer's neurofibrillary change distribution in myotonic dystrophy. AB - Histological changes that explain the mental symptoms of patients with myotonic dystrophy (MD) have not fully been demonstrated yet. Recently, the presence of Alzheimer's neurofibrillary changes (ANCs) in the brain have been reported in this disease. We studied the brain of a 61-year-old male with MD. The distribution of ANCs was investigated and mapped through careful histological examinations. The examinations disclosed that in MD, ANCs distributed along their preferential sites of the brain; a great number of ANCs were found in the parahippocampus, hippocampus, amygdaloid nucleus, fusiform gyrus, insula, and olfactory bulb, many in the nucleus basalis of Meynert, inferior temporal gyrus, hypothalamus, and brain stem, and a few in the cingulate, frontal and temporal gyri, neostriatum, and mammillary body. In the brain stem, ANCs were seen in the central gray, oculomotor nucleus, linear nucleus, substantia nigra, locus coeruleus, dorsal raphe nucleus, superior central nucleus, retriculotegmental nucleus, and reticular formation. From this result and the previous reports by others, it may be suggested that the presence of ANCs concentrated mostly in the limbic system is a regular and significant histological finding in the brain in MD. Therefore, this limbic lesion must be related to some of the mental symptoms unique to MD. In addition, diffuse and considerable neuronal atrophy and gliosis in the thalami in the absence of ANCs also may have played a causative role in some of the mental symptoms of the present case. Besides the more concentrated occurrence of ANCs within the limbic system, the minimal presence of senile plaques in the CNS may differentiate the brain in MD from that in Alzheimer-type dementia. PMID- 2272144 TI - Alzheimer's neurofibrillary changes in the olfactory bulb in myotonic dystrophy. AB - The olfactory bulbs and stalks were examined in a case of myotonic dystrophy that showed numerous Alzheimer's neurofibrillary changes (ANCs) in the brain. Typical ANCs were found in the cell body of many mitral cells and tufted cells and of a few outer and inner granule cells. In addition, massive ANCs were present in the anterior olfactory nucleus, where almost all the nerve cells were affected by ANCs. No senile plaque was detected anywhere in the bulb and stalk. Electron microscopy disclosed that the ANCs were composed of paired helical filaments and straight tubules. This implies that there was no ultrastructural difference between ANCs in the bulb and those in the parahippocampus or hippocampus in the present case, as well as in Alzheimer's disease. These data indicate that in myotonic dystrophy mitral cells, tufted cell and granule cells, as well as anterior olfactory nucleus cells can be affected by ANCs. PMID- 2272145 TI - Entrapped, non-neoplastic adenohypophysiocytes in human pituitary adenomas. AB - The immunoprofile of 76 human pituitary adenomas was studied with particular reference to the occurrence of entrapped, non-neoplastic pituitary cells. This phenomenon was defined as unevenly distributed, usually peripherally located cells forming less than 1% of the total cell population. The stellate contour of such passively incorporated cells departed from the more rounded shape of most principal, neoplastic cells. Thirty-six of the adenomas studied comprised one or more types of entrapped elements. According to the hormone produced, prolactin (PRL-)cells most commonly occurred as a minor "foreign" component (seen in 23 of the adenomas), whereas growth hormone-(GH-) and adrenocorticotropic hormone-(ACTH )cells rarely were trapped (seen in 5 and 4 of the adenomas. Entrapped follicle stimulating hormone-(FSH-), luteinizing hormone-(LH-), and thyroid-stimulating hormone-(TSH-)cells assumed an intermediate position (seen in 14, 17 and 15 of the adenomas, respectively). PMID- 2272146 TI - Degeneration of posterior column nucleus, inferior olivary nucleus and cerebellar cortex: system degeneration of paraneoplastic disease? AB - Degeneration of the posterior column nucleus, inferior olive, and cerebellar cortex is reported in a cancer patient. A 70-year-old man developed an ataxic gait and rapidly progressive disturbance of deep sensation over six months, followed by an abasic state. Early well-differentiated tubular adenocarcinoma was detected and total gastrectomy was performed. He died due to pulmonary tuberculosis about two years and nine months after the operation. Degeneration of the posterior column nuclei was found, explaining the disturbance of deep sensation noted in the clinical course, although there were few changes in the peripheral nerves, dorsal root ganglia, and spinal cord. Degeneration of the inferior olive and cerebellar corte was also found. Metastatic small cell carcinoma was present in the right pulmonary hilar and paratracheal lymph nodes at autopsy without any detectable primary focus. There was neither recurrence nor metastasis of the gastric carcinoma. This is the first case report of this type of central nervous system degeneration in a cancer patient, and its pathogenesis and etiology remain obscure. We discuss whether system degeneration or paraneoplastic degeneration was the etiology. PMID- 2272147 TI - HLA-antigens in a Tunisian familial chondrocalcinosis. AB - Thirty members of a Tunisian family with hereditary chondrocalcinosis were typed for HLA-A, B, and DR antigens: 7 affected and 23 unaffected subjects in three consecutive generations. The haplotype A1 B12 DR3 was found in all affected subjects and in 8 unaffected members. Chondrocalcinosis in this family may be associated with the haplotype A1 B12 DR3. The mode of transmission was autosomal dominant with incomplete penetrance. PMID- 2272149 TI - Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein GP120 epitopes correlates with the uninfected status of children born to seropositive mothers. PMID- 2272148 TI - Xeroderma pigmentosum: clonal chromosomal rearrangements in a pre-cancerous skin lesion. AB - In cells from a papulonodular formation of a patient with the clinical and cellular phenotype of the variant form of xeroderma pigmentosum (XP-V), clonal rearrangements involving different chromosomes were observed. This finding confirms the literature data suggesting that multiple non-specific chromosome anomalies are typical of pre-malignant and malignant skin lesions. PMID- 2272150 TI - The same 50-kDa cellular protein binds to the negative regulatory elements of the interleukin 2 receptor alpha-chain gene and the human immunodeficiency virus type 1 long terminal repeat. PMID- 2272151 TI - Moricizine: a new class I antiarrhythmic. AB - The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of the Class I antiarrhythmic agent moricizine hydrochloride are reviewed. Moricizine is chemically similar to the phenothiazines but does not appear to block dopaminergic receptors. Its major electrophysiologic actions are a concentration-dependent decrease in maximum rate of phase 0 depolarization; increased rates of phase 2 and 3 repolarization, decreased action potential duration, and decreased effective refractory period. Moricizine causes a dose related prolongation of the PR interval and of AV nodal, infranodal, and intraventricular conduction times but has little effect on ventricular repolarization. The antiarrhythmic and electrophysiologic effects are not correlated with plasma concentrations of the drug or its metabolites. Moricizine reduces the occurrence of ventricular premature contractions (VPCs), couplets, and nonsustained ventricular tachycardia. It appears to suppress symptomatic nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation or flutter. Moricizine appears to be as effective as quinidine and more effective than disopyramide, propranolol, and imipramine but less effective than flecainide and encainide at reducing VPCs. Moricizine continues to be evaluated in the Cardiac Arrhythmia Suppression Trial, which was designed to assess the long-term benefit of arrhythmia suppression in patients with left ventricular dysfunction after myocardial infarction. Moricizine seems to be better tolerated than quinidine, disopyramide, and imipramine and to have less proarrhythmic potential than flecainide or encainide. Noncardiac adverse effects include dizziness, nausea, and headache. Cimetidine appears to decrease moricizine clearance, and decreased theophylline clearance has been reported in subjects given moricizine. The usual adult dosage of moricizine hydrochloride is 600-900 mg/day given in three divided doses; an every-12-hour regimen may be used in some patients. Because of the risk of proarrhythmic effects, indications are limited to treatment of documented life-threatening arrhythmias. Moricizine will compete with other agents as first-line therapy for life-threatening arrhythmias. PMID- 2272152 TI - Management of hypertension in the diabetic patient. AB - Therapeutic considerations regarding the treatment of hypertension in patients with diabetes mellitus are reviewed. Good blood pressure control is essential in diabetic patients to prevent morbidity and mortality associated with cardiovascular diseases. Hypertension may also accelerate complications of diabetic microvascular disease, nephropathy, and retinopathy. Diuretics (e.g., thiazides, furosemide, ethacrynic acid, bumetanide) and beta blockers have traditionally been used as initial therapy for most patients with hypertension; however, these agents may not be the best choice for diabetics. Adverse metabolic consequences include alteration of glucose metabolism and plasma lipids. Beta blockers may also blunt the ability of patients to recognize symptoms of hypoglycemia. Both diuretics and beta blockers can cause sexual dysfunction in men. Adrenergic agents and vasodilators are associated with a high prevalence of orthostatic hypotension in diabetic patients. The calcium-channel blockers are considered safe and well tolerated when given at low and moderate doses. The angiotensin-converting-enzyme (ACE) inhibitors are able to slow the progression of diabetic nephropathy by reducing the glomerular hypertension that causes it. For the treatment of mild hypertension in diabetic patients, the drugs of choice should include (in descending order) ACE inhibitors, calcium-channel blockers, diuretics, and beta blockers. Severe or resistant hypertension usually requires treatment with combinations of drugs, including a diuretic. Tailoring therapy to individual complications and close monitoring of the patient are essential for safe, effective treatment of hypertension in the diabetic patient. PMID- 2272153 TI - Effect of hydrochlorothiazide 25 mg/day on essential hypertension. PMID- 2272154 TI - Criteria for use of amrinone lactate in hospitalized adult patients. PMID- 2272156 TI - Interrelationship between platelet count, red cell count, white cell count and weight in men. AB - In 83 healthy normotensive males aged 20-55 years the platelet count is positively correlated with the red cell count (r = 0.371; P = 0.0006), the white cell count (r = 0.358; P = 0.0009), and with weight (r = 0.252; P = 0.0269). The red cell count is also positively related with the white cell count (r = 0.242; P = 0.0278) and with weight (r = 0.326; P = 0.0039); while the white cell count is slightly correlated with weight (r = 0.210; P = 0.067). These findings provide further indirect evidential support for a haemopoetic growth factor acting on a single pluripotent stem cell. PMID- 2272155 TI - The value of the erythrocyte indices as a screening procedure in predicting nutritional deficiencies. AB - The results of a large number of nutritional screen requests (n = 871) were compared with corresponding values of erythrocyte indices considered predictive of nutritional deficiencies to determine if such indices could be used in a prospective screening procedure to restrict the number of serum vitamin B12, folate, and ferritin assays. Low mean cell haemoglobins (MCH less than 27 pg) were found to be superior to low mean cell volumes (MCV less than 77 fl), in predicting low serum ferritin values. The occurrence of deficient ferritin values was 90% when the MCH was very low (MCH less than 23 pg). Vitamin B12 or folate deficiency could not be predicted from the MCV. A normal MCV was found in more than 55% of vitamin B12 deficient samples and some 30% of serum B12 deficients (less than 150 micrograms/l) showed no evidence of anaemia (Hb greater than 12 gm/dl) or macrocytosis (MCV less than 100 fl). It would not seem appropriate to use erythrocyte indices alone as a method of selecting samples for further investigation of folate or vitamin B12 status. PMID- 2272157 TI - Recurrent acute renal failure complicating IgG warm-type autoimmune intravascular haemolysis. AB - A 44-year-old woman experienced recurrent episodes of massive intravascular haemolysis complicated by acute oliguric renal failure over a period of 22 years. The haemolysis was induced by IgG warm type autoantibody and complement and responded to corticosteroid therapy. The renal failure was treated effectively by dialysis. To our knowledge, such a life long occurrence of recurrent intravascular haemolysis induced by IgG warm type autoantibodies together with renal failure has not been reported before. PMID- 2272158 TI - Reticulocyte count using thiazole orange. A flow cytometry method. AB - Recently flow cytometry techniques have been developed to replace the microscope reticulocyte count. We used thiazole orange, a RNA binding fluorochrome, to discriminate reticulocytes from mature erythrocytes. Thiazole orange and the Retic-COUNT software package were evaluated for performance of routine analysis on different flow instruments. The applied methodology analysed 10(4) cells semi automatically in an easily performed manner. Consistent results were obtained with dipotassium EDTA anticoagulated blood (stable for 30 h after venesection), with incubation times in thiazole orange solution ranging from 2 to 7 h at 25 degrees C. This allowed flexibility in specimen collection and storage and assay performance with no change in results. Changes of incubation temperature up to 30 degrees C had no measurable effect. The values obtained showed good linearity, precision and accuracy for normal, low and high reticulocyte counts. However interferences were observed: RBC autofluorescence, nucleated RBC, Howell-Jolly bodies, high leucocyte count, high platelet count and giant platelets, all falsely increased the number of reticulocytes. These artifacts were eliminated by software gate corrections, thus leaving less than 5% of the specimen to be reanalysed by the microscopic method. The thiazole orange flow cytometric method was determined to be a fast, reliable method for the routine clinical quantitation of reticulocytes. PMID- 2272159 TI - Purification of human megakaryocytes using a glycoprotein Ib dependent agglutination technique. AB - In order to study normal and abnormal human megakaryocytopoiesis we modified a glycoprotein Ib dependent megakaryocyte purification technique originally described in guinea pigs. After Percoll density centrifugation, 2 ml bone marrow aspirates were subjected to 3 steps of bovine plasma induced cell clumping, which should selectively agglutinate glycoprotein Ib positive cells. In 13 experiments the resulting samples contained 28-102 x 10(3) megakaryocytes (median 70) with a median purity of 79%. Megakaryocyte recovery ranged from 30-86% (median 51%). The DNA profile showed median values of 10% for 8 N, 44% for 16 N and 43% for 32 N megakaryocytes. The described method is relatively simple, inexpensive and gives results comparable with more elaborate techniques. PMID- 2272160 TI - Guidelines for implementation of a maximum surgical blood order schedule. The British Committee for Standards in Haematology Blood Transfusion Task Force. PMID- 2272161 TI - Guidelines on product liability for the hospital blood bank. The British Committee for Standards in Haematology. AB - This report aims to clarify the position of the hospital blood bank in the light of product liability legislation contained in the Consumer Protection Act of 1987. Blood has been defined a 'product' under this Act. The potential for the blood bank to be seen in the role of 'supplier', 'keeper' or even 'producer' in the chain of product supply to the patient is explained and advice given on the resulting implications for blood bank practice. It will be necessary to define, adopt and implement standard operating procedures (SOP) for all blood bank activities. Guidance is given on the format, preparation and content of SOPs and specimen examples offered. The fundamental importance of quality assurance is emphasized. PMID- 2272162 TI - Computer-assisted linearization of the von Krogh Curve for the measurement of serum complement titre. AB - Computer simulations of complement titre measurement in sera by linearizing the sigmoidal curve of complement dose response were performed, to simplify the logarithmic calculations of CH50 values. CH50 titres of large variety of human sera including healthy donors and immune deficiency patients were estimated. The values obtained were compared with the hand-simulated results using the Y/(1-Y) conversion table and a log-log graphic paper. Using computer simulation, CH50 can be determined with great ease. PMID- 2272163 TI - Bronchopericardial fistula and pneumopericardium complicating invasive pulmonary aspergillosis. PMID- 2272164 TI - Danazol therapy in familial antithrombin III deficiency. PMID- 2272165 TI - On the occurrence of isolated reticulocytopenia and erythroblastopenia with maturation arrest and dyserythropoiesis. PMID- 2272166 TI - On the haemolytic anaemia called 'the phenomenon of the Danaide'. PMID- 2272167 TI - The biology of myelopoiesis. AB - The myelopoietic system includes the hematopoietic cells derived from a common hematopoietic stem cell that includes erythroid, granulocytic, monocytic, and megakaryocytic lineages. The contributions of molecular genetic techniques to hematopoiesis in the past 5 years have led to quantum leaps in our understanding, but there is room for further research. Current concepts of stem cells and the hematopoietic microenvironment are discussed, as are committed progenitor cells and hematopoietic growth factors, particularly those concerning the neutrophilic, monocytic, and erythroid systems. PMID- 2272168 TI - Myeloproliferative disorders. PMID- 2272169 TI - Classifications of acute myeloid leukemia. AB - A detailed description of the various subtypes of the acute myeloid leukemias is provided. The importance of cytochemistry and monoclonal antibodies is discussed. PMID- 2272170 TI - Diagnosis, classification, and course of myelodysplastic syndromes. AB - The myelodysplastic syndromes are bone marrow stem cell disorders that result in disorderly and ineffective hematopoiesis. They are prognostically heterogenous. Approximately one third of cases evolve to acute myeloid leukemia. Many additional cases terminate in severe bone marrow failure. The French-American British Working Group classification of the myelodysplastic syndromes defines morphologic and prognostic groups. Cytogenetic and in vitro cell culture characteristics are important prognostic indicators. PMID- 2272171 TI - Immunophenotyping of acute myeloid leukemia cells. AB - This article considers the expression of myeloid cell-associated antigens on both normal and malignant myeloid cells. Progress in the use of monoclonal antibodies to myeloid cell surface antigens for the diagnosis, subclassification, and treatment of acute myeloid leukemia is discussed. The results of bone marrow purging with monoclonal antibodies to remove leukemia cells for the purpose of autologous bone-marrow transplantation are promising. PMID- 2272172 TI - Leukemias of indeterminant lineage. AB - Two biologically and clinically important forms of acute leukemia have been described. Evidence suggests that both undifferentiated acute leukemia and many types of hybrid leukemia arise from relatively fewer differentiated cells than do the more straightforward acute leukemias. Clinical correlations suggest that patients with these leukemias may have a poorer prognosis, although some findings may be associated with an improved prognosis. More data in which multiple techniques are applied to the same leukemic cells are clearly needed. Patients with certain types of hybrid leukemias may be suitable candidates for more aggressive forms of chemotherapy or, possibly, combinations of therapy directed at cells of both lineages. PMID- 2272173 TI - Chromosomal abnormalities in myelodysplastic syndromes and acute myeloid leukemia. AB - Clonal chromosome abnormalities are found in more than half the patients with hematologic malignancies. Karyotype is an independent prognostic factor in these patients. Cytogenetic findings correlate significantly with morphologic, immunologic, and clinical features as well as response to treatment, remission duration, and survival. The number of different cytogenetic abnormalities is enormous; however, many cytogenetic findings frequently occur in a given disease (e.g., abnormalities of 5 or 7 in 75% to 90% of patients with therapy-related AML). Some abnormalities are found only in myeloid malignancies, for example, the t(8;21)(q22;q22) and rearrangements of chromosome 16q22, both of which have a good prognosis. Other abnormalities usually are found in both myeloid and lymphoid malignancies, for example, the t(4;11)(q21;q23) and t(9;22)(q34;q11), both of which have a poor prognosis. The Human Gene Mapping Conferences have compiled much cytogenetic data and produced several interesting correlations in myeloid malignancies: rearrangements of 3q21-26 with myeloid proliferations associated with environmental exposure (similar to abnormalities of 5q, 7q, 12p, and 17q), aberrations of 12p, 11q13 and 11q23 with both myeloid and lymphoid disorders, and the lack of myeloid involvement and abnormalities of chromosomes 14 and 18. In conclusion, cytogenetic analysis of neoplastic cells at diagnosis for patients with MDS, AML, and SAML is required for appropriate diagnosis and treatment. The use of chromosome abnormalities to separate patients into high- and low-risk groups eventually may allow us to be more effective in selecting curative therapy. PMID- 2272175 TI - Systems used to study the nature of the leukemic cell and predict treatment outcome in patients with myeloproliferative disorders. AB - Cell culture techniques have been used to study normal and leukemic hematopoiesis. Investigations provided data on the nature of the clonogenic leukemic cell, its patterns of in vitro growth, role of stimulating factors, and effects of chemotherapeutic agents. Assay systems developed to study leukemic progenitor cells or self-renewal capacity have been useful clinically as predictive indicators of success of remission-induction therapy and have allowed testing of drug sensitivity in vitro. Alternative approaches using short- and long-term suspension cultures have provided systems to evaluate leukemic cells, including nonclonogenic, biochemical, and kinetic events. In vitro systems have been introduced to measure cell cycle events accurately and to identify metabolic mechanisms of drug resistance. The information provided by all of these systems has allowed a more comprehensive and multifocal characterization of the nature of the leukemic process and has better directed our approach to treatment. PMID- 2272174 TI - The role of ras gene mutations in myeloproliferative disorders. AB - Mutations in the ras genes frequently are found in myeloproliferative disorders. These abnormalities have prognostic significance in the myelodysplastic syndromes, but their clinical importance in other hematopathic states remains unclear. The study of this gene in leukemic conditions is providing insights into the genetic pathways leading to leukemic progression. PMID- 2272176 TI - Myeloproliferative disorders. Classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia. AB - Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages. Transitions among the different CMPD and termination in acute leukemia or marrow failure also are common. CML often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes (mature and immature) in the blood and marrow, reduced LAP, hypercellularity with prominent granulocytic hyperplasia in the marrow, Ph chromosome, and bcr-abl gene rearrangement. Typical features of AMM include leukoerythroblastosis, teardrop poikilocytosis, anemia, increased or normal LAP, prominent megakaryocytic hyperplasia in the marrow, dyshematopoiesis, and hyperplastic or fibrotic/sclerotic marrow. PMID- 2272177 TI - Molecular methods to detect the Philadelphia chromosome. AB - The Ph1 chromosome has two molecular subtypes: a bcr-positive seen in CML and some cases of ALL, and the bcr-negative subtype mainly seen in ALL. In CML, because of the restriction of chromosome 22 breakpoints to the bcr, Southern analysis to detect bcr rearrangements also can be used to detect the Ph1 chromosome. In contrast, the translocation breakpoints on the Ph1 chromosome are scattered in ALL, so that other methods such as PFGE and PCR are necessary to detect the Ph1 chromosome. In both CML and ALL, use of these methods to detect molecular abnormalities may be superior to cytogenetics in detecting chromosomal abnormalities. Southern analysis also can be used in CML to map breakpoint locations within the bcr. This may offer prognostic information as to the length of chronic phase, but there is conflicting information as to the validity of this approach. The modified PCR (using cDNA from mRNA) can be used to detect the Ph1 chromosome and to define which of the molecular subtypes are present. The exquisite sensitivity of this method, which is capable of detecting as little as a single abnormal molecule of RNA or DNA, makes it suited for the detection of minimal residual disease in both CML and ALL. This is particularly useful after intensive therapies, such as bone marrow transplantation. Whether these low levels of fusion gene expression are of prognostic significance is still unclear. PMID- 2272178 TI - Polycythemia vera and other polycythemic states. AB - The diagnosis of polycythemia requires an accurate and independent assessment of both plasma volume and red blood cell mass. Patients with an increased red cell mass (absolute polycythemia) may be hypoxic or have an erythropoietin-secreting tumor or space-occupying lesion compressing the kidney. Those with a reduced plasma volume (relative polycythemia) most often are tobacco smokers, are taking diuretic or cardiac medications, or ingest increased quantities of caffeine containing beverages. On the other hand, polycythemia vera is a systemic disease with multiple complications, which is best diagnosed through a complex of findings as outlined by the Polycythemia Vera Study Group. PMID- 2272179 TI - Platelet abnormalities in myeloproliferative disorders. AB - A large number of various platelet abnormalities are described in patients with MPD. These abnormalities serve diagnostic purposes only. They appear to have little or no predictive value regarding the clinical manifestations of the patients or the progress of the disease. Those platelet characteristics most consistently reported to be defective include a decrease in the platelet content of serotonin and adenine nucleotides, decreased platelet density, an abnormal ultrastructure characterized by paucity of granules and hypertrophy of the surface connecting canicular system, an altered membrane glycoprotein profile that includes reduced levels of GPIb, and reduced lipoxygenase activity and aggregation response with epinephrine. These abnormalities may originate at the megakaryocyte level. Furthermore, the released abnormal platelets may undergo modification of their functional and biochemical characteristics as a result of episodes of intravascular thrombosis or aging in circulation or as a result of the progression and treatment of the disease, thus creating the paradoxic and often conflicting relationship between the thrombotic and hemorrhagic events and the results of platelet functional tests as observed in this disorder. PMID- 2272180 TI - Granulocytic sarcoma. AB - Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations. It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors. Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis. PMID- 2272181 TI - Contraception survey: Denmark 1988. AB - In 1988 a survey** was conducted in 1,033 women living in Denmark, whose ages ranged from 15 to 44 years. The main aims of the study were to identify the influence, if any, of demographic and socioeconomic factors on contraceptive use and to assess the women's knowledge of selected facts concerning their own fertility. The study's additional objectives were to gain insight into factors influencing communication on the subject of contraception, such as advice obtained from professional counsellors, general information dissemination and discussion between partners, and to investigate women's attitudes and opinions regarding contraceptive methods and their use. The results are discussed in relation to the findings of other studies on the use of contraceptives both worldwide and in a number of European countries. The Danish findings are also examined in the context of possible action to reduce the relatively high rate of legally induced abortions in Denmark. PMID- 2272182 TI - Characteristics of condom use and associated problems: experience in Bangladesh. AB - Data from the 1983 Bangladesh Condom User Survey (BCUS) are analyzed for patterns of condom use and various problems directly influencing their effectiveness. The survey was undertaken to explain an apparent gap between reports of the number of condoms distributed in certain areas compared with prevalence of users as reported in contraceptive prevalence surveys. These data are analyzed from behavioral and management perspectives to identify various factors influencing utilization, with potential implications for understanding and improving family planning and AIDS/STD prevention service systems. Patterns of use are related to differences in source of supply through public, free or private-priced systems, differences in urban or semi-rural place of residence, and differences in perceptions of men or women. The problem with condom use most often identified by the respondents was breakage. PMID- 2272183 TI - Milk and plasma concentrations of the progestin ST-1435 in women treated parenterally with ST-1435. AB - A subcutaneous contraceptive capsule releasing progestin ST-1435 was used by 6 breast-feeding women. One to three paired milk and plasma samples were collected over a one-month period and the concentrations of ST-1435 were determined by radioimmunoassay. An improved and sensitive method for determination of ST-1435 in milk was developed. A column chromatographic purification of milk prior to radioimmunoassay decreased the blank and improved sensitivity. The average plasma concentration of ST-1435 was 62 +/- 20 pg/ml (mean +/- SD). The average milk concentration of ST-1435 was 38 pg/ml (ranging from 7 to 73 pg/ml), while the average milk to plasma ratio was 0.60 (ranging from 0.25 to 0.91). There was a significant correlation between ST-1435 concentrations in breast milk and plasma, indicating that the concentration in plasma is the major determinant for the amount of ST-1435 excreted into milk. Since studies with this drug have shown good contraceptive efficacy and low bioavailability after oral intake, ST-1435 is a good candidate for lactational contraception. PMID- 2272184 TI - Contraception with a vaginal ring releasing 3-keto desogestrel and ethinylestradiol. AB - Eleven healthy women used a contraceptive vaginal ring for three cycles. The rings released 15 micrograms of ethinylestradiol and 150 micrograms of 3-keto desogestrel per 24 hours. The rings were used for 21 days and then removed, rinsed in clean water and stored. After a 7-day ring-free period, the rings were reinserted. Totally, each ring was used for 3 cycles. The rings were well tolerated. The bleeding pattern was excellent. No woman showed any signs of ovulation when using the ring. Estradiol levels were suppressed, but showed an increase during the ring-free period as can be found during the pill-free period of an oral contraceptive regimen. When the ring was reinserted, the estradiol levels were rapidly suppressed again. SHBG capacity increased during use of the ring. PMID- 2272185 TI - Gossypol-induced inhibition of glucose uptake in human ejaculated spermatozoa may be mediated by lipid peroxidation. AB - Gossypol, a plant-derived polyphenolic compound known to exert contraceptive actions in men, inhibits 14C-glucose uptake in vitro in human ejaculated spermatozoa. Spermatozoal glucose uptake was found to increase monotonically up to 40 min, and then decreased by 60 min, possibly because of the saturation of the transport loci in the membrane. Gossypol at the concentrations of 5 and 10 microns caused a reduction of both the linear portion of the uptake and the fall afterwards. Gossypol similarly affects both the Na-dependent and -independent glucose uptake. The kinetic parameters of glucose uptake indicate that gossypol might be interfering with the transport/carrier protein as reduction in maximum uptake velocity (Vmax) was observed without any change in the affinity constant (Km). Similarly, gossypol also produced an increase in spermatozoal lipid peroxidation as evidenced by a steep rise in thiobarbituric acid reaction products in the human sperm cells. A significant decrease in total phospholipid level and the individual classes was noted after gossypol addition. Gossypol induced inhibition of glucose uptake may be related to the generation of lipid peroxides and consequent membrane damage. PMID- 2272186 TI - Effect of vasectomy on in situ pH in rat testis and epididymis. AB - The effect of bilateral vasectomy on in situ pH in seminiferous tubules, initial segments, proximal caput, middle corpus and proximal cauda epididymides of the rat has been studied employing in vivo microelectrode techniques. After bilateral vasectomy of four weeks duration, a significant increase in acidity of luminal fluid in the initial segments of the caput epididymides was observed. By eight weeks post vasectomy, luminal pH in the initial segments was significantly more acid as compared to sham-operated control animals or four weeks vasectomy while, in contrast, luminal pH in the proximal cauda epididymides was significantly more alkaline. The alteration of luminal fluid pH in the initial segments and proximal cauda epididymides after bilateral vasectomy may be the result of impairment of acid-base, as well as water transport pathways. PMID- 2272187 TI - Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of osteoarthritis: a comparative controlled clinical trial in general practice. AB - A double-blind, crossover study was undertaken in general practice to compare the efficacy and tolerability of a new controlled-release indomethacin with sustained release diclofenac sodium in patients with osteoarthritis. Eighty-four patients were randomly allocated to receive controlled-release indomethacin tablets (75 mg) or sustained-release diclofenac sodium tablets (100 mg) at night for a period of 4 weeks before being crossed-over to receive the alternative treatment for a further 4 weeks. Pain scores for day and night, duration of morning stiffness, requirement for escape analgesia, and treatment preference were similar for both treatments. There was no significant difference between treatments for incidence and severity of side-effects. It was concluded that controlled-release indomethacin tablets (75 mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100 mg). PMID- 2272188 TI - Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of rheumatoid arthritis: a comparative controlled clinical trial. AB - The efficacy and tolerability of a new, controlled-release indomethacin (75 mg) tablet was compared to that of a sustained-release diclofenac sodium (100 mg) tablet in 84 patients with rheumatoid arthritis. The study was designed as a double-blind, double-dummy crossover trial, patients being allocated at random to receive 1 active tablet and 1 placebo tablet of the alternative medication at night for 4 weeks before being crossed over to the alternative treatment for a further 4 weeks. Patient and clinical assessments on entry and at the end of each treatment period showed that pain scores for day and night, duration of morning stiffness, requirement for escape analgesia (paracetamol) and treatment preference were similar for both treatments. Both preparations also significantly improved the degree of joint tenderness compared to baseline (p less than 0.001), as measured by a modified Ritchie Articular Index. Incidence and severity of side effects were comparable, with a significant improvement in degree of constipation reported for both treatments compared to baseline (p less than 0.05). The incidence and severity of headache was statistically significantly worse (p less than 0.05) for controlled-release indomethacin; however, there was no difference in any other parameter of tolerability. It was concluded that controlled-release indomethacin tablets (75 mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100 mg). PMID- 2272189 TI - Bumetanide/amiloride ('Burinex A'): a new combined preparation for the control of patients with congestive cardiac failure. AB - Two hundred and thirty-three patients (66 males and 167 females), aged 24 to 92 years, with congestive cardiac failure were entered into a long-term study to evaluate the efficacy and tolerability of treatment with a fixed dose combination tablet containing 1 mg bumetanide and 5 mg amiloride. One hundred and fifty-five patients were treated for 52 weeks. The daily dosages were 1 tablet (113 patients), 2 tablets (35 patients), 3 or 4 tablets (7 patients). Treatment was associated with a marked reduction in the prevalence of ankle oedema, dyspnoea and pulmonary crepitations, and with statistically significant decreases in body weight, pulse rate and calf measurement. Mean serum potassium showed a small but statistically significant increase, but serious hyperkalaemia was not encountered. Although serum sodium decreased, serious hyponatraemia did not occur. No clinically significant effects on hepatic, renal or haemopoietic function were observed. Minor adverse effects, most of which resolved spontaneously, were reported by 60 patients. Only 14 (6.0%) patients ceased treatment because of adverse effects. PMID- 2272190 TI - Efficacy and tolerability of controlled-release trazodone in depression: a large multicentre study in general practice. AB - A double-blind, parallel-group study was carried out to compare the efficacy and tolerability of a controlled-release tablet formulation of trazodone with the standard trazodone tablet. Three hundred and forty-seven general practice patients with depressive symptoms were recruited into the trial. Patients were randomly allocated to receive either 1 controlled-release trazodone (150 mg) tablet at night or 1 standard trazodone (150 mg) tablet at night for a period of 6 weeks. Assessments of efficacy, tolerability and compliance were made at study entry and after 1, 2, 4 and 6 weeks of study medication. Seventy-seven patients withdrew from the study of whom 44 were in the standard trazodone tablet group and 33 were in the controlled-release trazodone tablet group. There were no statistically significant differences between treatment groups in any of the measures of efficacy (global severity, global improvement and Hamilton Depression Rating Scales 17- and 21-item). Major improvements in patients' condition were shown in all efficacy measures by the end of the study in comparison with study entry. Treatment differences were small but were numerically in favour of the controlled-release tablet formulation. As expected, a greater proportion of side effects were reported during the first 2 weeks of treatment in both groups. Treatment differences, revealed in a five symptom adverse event checklist used throughout the study, were small, although in favour of the controlled-release tablet in the majority of cases, but not statistically significant. PMID- 2272191 TI - Double-blind, placebo-controlled clinical trial of a mixture of gangliosides ('Cronassial') in post-herpetic neuralgia. AB - A double-blind, parallel-group clinical trial was carried out in 25 patients with post-herpetic neuralgia to determine the efficacy and tolerability of a mixture of gangliosides ('Cronassial') compared with placebo. Patients were allocated at random to receive treatment with either 'Cronassial' (100 mg in 2 ml buffered solution) or placebo given by 11 subcutaneous injections over a period of 27 days, and their symptoms assessed on entry and after 2, 4 and 8 weeks. The four aspects of pain considered (overall pain, hyperaesthesia, stabbing pain and constant ache) all showed maintained reductions in severity with 'Cronassial' treatment, but not with placebo. In the case of hyperaesthesia, this difference between treatments was statistically significant (both during and after the course of injections), even with the relatively small number of patients in this study. Sleep patterns showed significant sustained improvements with 'Cronassial', but not with placebo treatment. Other psychological assessments (general psychological state, appetite and mood) showed little difference between 'Cronassial' and placebo treatment. Although 'Cronassial' was well tolerated systemically, 1 of the 12 patients was withdrawn because of general malaise, and 5 patients had local pain at the injection sites. Two of these 5 patients were withdrawn from the study. There were no withdrawals in the placebo group. It is suggested that further studies employing greater numbers of patients should be carried out to confirm the efficacy of gangliosides in improving symptoms of patients with post-herpetic neuralgia. PMID- 2272192 TI - Etizolam versus placebo in the treatment of panic disorder with agoraphobia: a double-blind study. AB - Thirty out-patients suffering from panic disorders associated with agoraphobia were enrolled in a double-blind, controlled trial to compare the effectiveness and tolerability of etizolam and placebo. After a 1-week washout period on placebo, patients were allocated at random to receive twice daily doses of either 0.5 mg etizolam or placebo over a period of 4 weeks. Assessments, made at baseline and after 2 and 4 weeks of treatment, used the Hamilton Rating Scales for Anxiety and for Depression, the Covi Anxiety Scale, and determination of the weekly panic crises frequency. The results showed that etizolam produced significant improvements in chronic anxiety, phobic ideas, associated depressive symptoms and episodic anxiety, and was significantly more effective than placebo. Etizolam treatment was generally well tolerated and was not significantly different from placebo in this respect. PMID- 2272193 TI - Depression in general practice: a comparison of flupenthixol dihydrochloride and dothiepin hydrochloride. AB - A single-blind, parallel group, general practice study was carried out in 153 patients with mild to moderate depression to compare the efficacy and tolerability of flupenthixol dihydrochloride and dothiepin hydrochloride. Patients were allocated at random to receive single daily doses of either 1 mg flupenthixol in the morning or 75 mg dothiepin in the evening, and this dose could be doubled at the end of 2 weeks in the event of inadequate response. Assessments were made on entry and after 1, 2, 4 and 6 weeks of treatment using the Hamilton Depression Rating Scale, a 4-point severity scale and an unwanted symptoms checklist. The results showed that both treatments significantly improved the patients' condition over 6 weeks, and there was a significant difference in favour of flupenthixol at end-point. Both drugs were well tolerated, although persistence of anticholinergic side-effects in the dothiepin group resulted in a trend favouring flupenthixol. One patient in the flupenthixol group attempted suicide by overdose but made a complete recovery. PMID- 2272195 TI - Therapeutic hemapheresis in the 1990s. PMID- 2272194 TI - Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy. AB - An open, multi-centre, general practice study was carried out in 1661 asthmatic patients to assess the efficacy, in terms of symptom relief and changes in lifestyle, of budesonide and to record objective lung function changes and any adverse events. After a 1-week run-in period on any pre-trial anti-asthma medication, patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks. Peak expiratory flow rate (PEFR) was measured by the doctor on entry, after the run-in, and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance, bronchodilator usage and the severity of cough, wheeze and sleep disturbance, and weekly to record 5 lifestyle assessments, e.g. physical activity. Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 +/- 3 l/min at the end of the run-in to 368 +/- 3 l/min at the end of the trial; 77% of patients had an improved PEFR. Bronchodilator use decreased significantly from 4.2 +/- 0.1 times/day during the run-in period to 3.0 +/- 0.1 times/day at the end of the study; 65% of patients used less bronchodilator. Significant improvements were recorded in all the symptoms and lifestyle indices monitored; 76% of patients improved in at least 5 of the 11 assessments. Treatment-emergent adverse events occurred in 103 (6%) of patients: none was classified as serious or unexpected. No sub-group of patients was identified in which the results were at variance from the full sample. It is concluded that budesonide improves patients' lifestyle and ability to carry out normal activities, as well as improving PEFR and reducing bronchodilator use, in mild to moderately severe asthmatics treated in general practice. PMID- 2272196 TI - Apheresis in transition. PMID- 2272197 TI - The risk/benefit equation for therapeutic plasma exchange. Analysis of the rationale for and the safety aspects of therapeutic plasma exchange. PMID- 2272198 TI - Plasma exchange in thrombotic thrombocytopenic purpura. PMID- 2272199 TI - Plasma exchange in idiopathic thrombocytopenic purpura. PMID- 2272200 TI - Plasma exchange in neurology. PMID- 2272201 TI - Plasmapheresis to treat human T lymphotropic virus type I-associated myelopathy. PMID- 2272202 TI - Experience with low-density lipoprotein apheresis by polyclonal and monoclonal anti-apolipoprotein B antibodies and by dextran sulfate cellulose. PMID- 2272203 TI - Viscosity as the symptom leading to plasma exchange. PMID- 2272204 TI - The current status of low-density lipoprotein apheresis. PMID- 2272205 TI - Ex vivo activation and retransfusion of white blood cells. The immunotherapy of cancer. PMID- 2272206 TI - Prevention and circumvention of refractoriness to platelet transfusions: interface between preparative and therapeutic apheresis. PMID- 2272207 TI - Available removal systems: state of the art. PMID- 2272208 TI - Chemotaxis of human blood monocytes. Methodological and clinical aspects. PMID- 2272209 TI - Methodological problems in bone histomorphometry and its application in postmenopausal osteoporosis. PMID- 2272210 TI - An experimental study on silver in the nervous system and on aspects of its general cellular toxicity. AB - Exposure of foetal and adult rats to silver results in a long-lasting deposition of the metal in many structures of the nervous system. A brief anatomical description of the localization of silver deposits as they are visualized by autometallography is provided. The consequences of silver in the nervous system were evaluated by volumetric measurements on developing rat hippocampi which showed that silver induced a decrease in the total volume of hippocampal pyramidal cells. The toxicity of silver at the cellular level was studied in a test-system of cultured macrophages. High doses of silver caused coagulation necrosis, whereas lower concentrations resulted in a cytotoxic and possibly a cytostatic effect without affecting cell structure. The processing of silver which resulted in lysosomal accumulations was affected by the metal itself in a dose-dependent fashion (autointerference). Other basic macrophage functions (protein-production, phagocytosis, migration) were not affected by silver at concentrations which did not cause acute cell death. Biochemically, silver causes an increase in lipid peroxidation, which was evident only in liver tissue. Coagulation necrosis and, to some extent, long-term effects on cell viability could be reversed by inorganic selenium, which was tested as a detoxicant. On the other hand, pre-exposure of animals to selenium greatly enhanced the silver induced lipid peroxidation. Furthermore, the co-exposure to silver and nickel resulted in a synergistically increased lipid peroxidation. PMID- 2272211 TI - Echocardiographic screening in 24 consecutive AIDS patients. AB - To assess the prevalence and extent of cardiac abnormalities in patients with newly diagnosed AIDS, 24 consecutive patients admitted for treatment for acute opportunistic infections were examined with echocardiography during hospitalisation. None of the patients had known cardiac disease or were drug abusers. A total of 16 abnormalities were identified in 13 patients (54%). Nine patients had a right ventricular diameter exceeding 26 mm, two patients had a slightly dilated left atrium or left ventricle, respectively, and five had a moderate pericardial effusion (range 2-8 mm). Left ventricular contractility was normal in all patients. Survival rates between AIDS patients with or without cardiac abnormalities were identical. It is concluded that minor cardiac abnormalities are common in AIDS patients with acute opportunistic infection. However, echocardiography in this group of AIDS patients without cardiac complaints gives no important functional or prognostic information as a routine procedure. PMID- 2272212 TI - External negative thigh pressure. Effect upon blood flow and pressure in the foot in patients with occlusive arterial disease. AB - We studied the effect of external application of 35-45 mmHg negative pressure around the thigh on toe blood pressure and skin blood flow in nine patients with occlusion of the superficial femoral artery and rest pain/severe intermittent claudication. The systolic toe blood pressure increased from 32 (range 5-70) mmHg before treatment to 57 (42-75) mmHg (p less than 0.05) during negative thigh pressure and 44 (range 10-88) mmHg after treatment. In addition, the gain in toe blood pressure tended to be greater the lower the pre-test toe pressure was, correlation coefficient r = 0.52 (p greater than 0.05). Relative skin blood flow, measured in the first toe interstice by the 133Xe wash-out method, increased by 304 (range 86-767) percent (p less than 0.05) during the test period compared to the mean wash-out rate obtained before and following the test period. Heart rate, systemic blood pressure, skin temperature, serum protein and haematocrit measured during each phase of the study were similar. We conclude that 35-45 mmHg negative pressure around the thigh in patients with occlusion of the superficial femoral artery induce increased blood perfusion in the foot, possibly due to changes in collateral arterial resistance in the thigh. PMID- 2272213 TI - Tuberculous meningitis. 23 cases from a 12-year period (1976-1987). AB - Twenty-three patients with tuberculous meningitis were reviewed to see whether clinical features or initial laboratory findings could discriminate between these patients and other patients with bacterial meningitis. Nineteen patients were Danes and four immigrants. Preexisting diseases were found in eight cases. Duration of symptoms could be related to neurological sequelae, but not to death. The initial clinical picture was indistinguishable from meningitis of other causes. Microscopy of the cerebrospinal fluid (CSF) was negative in all but two cases, where acid fast bacilli were found. CSF cytology and biochemistry could not discriminate from other causes bacteria of meningitis although CSF/blood glucose ratio in 56% was below 0.3. One of the most important pieces of information in establishing an early diagnosis in tuberculous meningitis is the anamnestic information, and therapy often has to be started without knowing the microbiological data. PMID- 2272214 TI - A dietary study of the elderly in the city of Roskilde 1988/89. Methodological aspects of the relative validity of the dietary history method. AB - In winter 1988/89, 194 elderly adults (96 men and 98 women, aged 70-75 years) were interviewed, using the dietary history method. The relative validity of a dietary history method used in this elderly population was assessed. The record of intake of energy and nutrients from the dietary history method was compared with that obtained in the same group by means of a 3-day food record completed during the same period. For daily intake of energy and nutrients, the differences in mean intake were generally below 15%. But mean differences were significant for energy, fat, dietary fiber, and calcium. The two dietary methods correlated well for energy and nutrients. Pearson's correlation coefficient varied from 0.80 (dietary fiber) to 0.24 (vitamin A). The two methods classified about half of the subjects similarly into tertiles for energy and most nutrients. Gross misclassification occurred for 2-17% of the subject. Agreement between the two methods were poorest for vitamin A. The results suggest that the dietary history method may be inadequate for determining the exact level of mean and distribution of dietary intake in a group or the precise intake of an individual. But the method could be used to test differences in means between groups and to rank subjects as to their dietary intake within the study. PMID- 2272215 TI - Extreme man-made stress and anti-therapy. Doctors as collaborators in torture. AB - Forty-nine torture survivors undergoing treatment between 1 March 1988 and 28 February 1989 at the Rehabilitation and Research Centre for Torture Victims (RCT) in Copenhagen entered a study to assess whether medical doctors had been involved in aspects of their torture. It became clear that the majority had indeed experienced this dimension of medicine. The participation of doctors in torture appears to be real and extensive and raises extremely serious questions as to medical accountability and responsibility. PMID- 2272216 TI - Effects of body position and bolus consistency on the manometric parameters and coordination of the upper esophageal sphincter and pharynx. AB - The development of a solid-state intraluminal sphincter transducer has alleviated many of the problems associated with manometric studies of the upper esophageal sphincter (UES) and pharynx (P). We used this technology to study the effect of position (upright vs. supine) on resting UES pressures and the pressure dynamics of the UES/P complex during both wet and dry swallows in 11 normal volunteers and the effects of foods of different consistencies on the UES/P swallow dynamics in 10 normal volunteers. The UES/P coordination parameters were defined as the 15 time intervals that can be measured between any 2 of 6 pertinent points: the beginning, peak, and end of the pharyngeal contraction and the beginning, nadir, and end of the UES relaxation. Data from both the circumferential transducer used to measure sphincter pressures and a standard microtransducer used to measure pharyngeal pressures were collected on-line by an Apple IIe microcomputer and analyzed by programs written in our laboratory. Significant changes in swallow coordination were measured between upright and supine swallows of the same bolus size, between wet and dry swallows in the same position, and among foods of varying consistencies. Resting UES pressure was unchanged by position and pharyngeal contraction pressure was unchanged by bolus size or consistency. PMID- 2272217 TI - Stationary vs. mapping manometry in evaluating dysphagia. AB - Two methods are used to assess esophageal motility. The mapping technique uses catheter withdrawal at 1 cm steps until the entire esophagus is evaluated. A simpler method is commonly used that involves keeping the catheter stationary for the entire evaluation. We compared these 2 techniques in 30 patients referred for the evaluation of dysphagia. Emphasis was placed on the distal 10 cm of the esophagus because this is the primary location of esophageal motility disorders. There was excellent correlation between techniques for mean distal amplitude (r = 0.945), mean distal duration (r = 0.942), and percentage of non-peristaltic contractions (r = 0.967). The overall manometry diagnosis was similar by both methods in 27 (90%) patients. Three patients had different manometry diagnoses resulting from use of the two techniques. However, the change in diagnosis was only clinically important in one patient in whom the mapping technique identified a segmental motility disorder that had been missed by the stationary technique. Stationary manometry had a 94% sensitivity and 93% specificity rate for identifying motility disorders compared to mapping manometry. We conclude that stationary manometry is a simple and accurate method for evaluating esophageal pressures and distal disorders. Only those patients with normal results of stationary studies may benefit by further mapping to identify rare segmental motility disorders. PMID- 2272218 TI - Radiographic techniques and efficacy in evaluating esophageal dysphagia. AB - The radiographic examination of the esophagus to determine structural and/or functional causes of dysphagia is best performed with multiple techniques. These include full-column studies to produce distended films with or without the use of a solid bolus, mucosal relief films to identify mucosal defects such as esophagitis or the presence of varices, double-contrast films, and motion recording (fluoroscopy). The efficacy of each technique depends on the quality of the study and the specific disorder to be detected. Esophageal lesions producing dysphagia are classified into extrinsic structural lesions, intrinsic structural lesions, and esophageal motility disorders. Radiographic studies are the preferred screening techniques for patients with dysphagia. Although not as sensitive for the evaluation of mucosal lesions, radiographic studies are superior to endoscopy for the detection of abnormal motility, esophageal rings, and strictures. PMID- 2272219 TI - Scleroderma esophagus. AB - Scleroderma (systemic sclerosis) is a connective tissue disorder characterized by thickening and fibrosis of the skin and visceral involvement that may include the heart, lungs, kidneys, and gastrointestinal tract. At least 40-50% of patients with scleroderma experience esophageal symptoms such as heartburn and dysphagia, while up to 90% of patients have esophageal dysfunction on objective testing at some point in their disease. The disease results in smooth muscle dysfunction that causes esophageal aperistalsis and reduced lower esophageal sphincter pressures. Gastroesophageal reflux with poor acid clearance results with an increased incidence of complications such as peptic stricture and Barrett's esophagus. Aggressive medical therapy is necessary to prevent these and other complications of gastroesophageal reflux. PMID- 2272220 TI - Esophageal motility, heartburn, and gastroesophageal reflux: variations in clinical presentation of esophageal dysphagia. AB - Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients. PMID- 2272221 TI - Symptoms of achalasia in young women mistaken as indicating primary anorexia nervosa. AB - The case of a young women with dysphagia, regurgitation, and weight loss, who was diagnosed as having anorexia nervosa but in whom reevaluation showed that achalasia was causing the symptoms, is presented together with related observations. Misinterpretation of esophageal symptoms may occur not only as a consequence of inadequate history taking and of being biased by a patient's emaciation, age, and gender, which leads to view certain aspects of the patient's history and behavior as suggesting a pathologic attitude towards eating and body weight, but also as a consequence of a misinterpretation of the symptoms as indicative of an eating disorder by the patients themselves. In some cases a disordered attitude toward eating and body weight may develop together or coexist with achalasia. The clinical evaluation of patients with symptoms suggestive of anorexia nervosa but also of bulimia nervosa should include the taking of a thorough history regarding swallowing and vomiting in order to recognize a possible esophageal motor disorder. PMID- 2272224 TI - [Periodontal environment of endosseous implants]. PMID- 2272222 TI - Esophageal perforation during pneumatic dilatation for achalasia: a possible association with malnutrition. AB - Pneumatic balloon dilatation of the lower esophageal sphincter is commonly utilized as primary therapy for achalasia. Perforation related to pneumatic dilatation is uncommon (2-6%) but may result in severe morbidity. Factors associated with risk of perforation are not well defined. We noted perforation in three patients undergoing forceful balloon dilatation. All these patients had clinical evidence of significant malnutrition (recent marked weight loss and severe hypoalbuminemia). Malnutrition may be a causal factor for perforation in patients with achalasia undergoing dilatation. PMID- 2272223 TI - [New concept of coronoradicular reconstruction: the Composipost (1)]. PMID- 2272225 TI - [Professional activities of the Society of German Surgeons in East Germany]. PMID- 2272227 TI - [Change in medical education with regard to practice from the perspective of surgery]. PMID- 2272226 TI - [Surgical endoscopy of the gastrointestinal tract in Austria. Critical considerations of the status with reference to 1987]. PMID- 2272228 TI - [Pleural empyema. Etiology, diagnosis and treatment guidelines]. PMID- 2272229 TI - [Lung abscess and bronchiectasis]. PMID- 2272230 TI - [Infections of the mediastinum]. PMID- 2272231 TI - [Pancreatico-pleural fistula. Clinical aspects and therapy of a rare disease entity]. AB - We report of 2 patients with pancreatic-pleural fistulas in chronic pancreatitis. In both cases abdominal symptoms were missed, the primary clinical manifestation was a recurrent pleural effusion with a high content of amylase. Endoscopic retrograde cholangiopancreaticography is necessary for a precise evaluation of the fistula and is indispensable to the surgical therapy. Computed tomography and ultrasonography showed in both cases a pancreatic pseudocyst. Our recommendation is surgical therapy when the fistula is not closed spontaneously within 2 weeks. Both patients were successfully treated by a left pancreatectomy. PMID- 2272232 TI - [The thyroid gland scintigram. A decision aid for the surgical approach in thyroid gland diseases?]. AB - For the operative proceeding thyroid scintiscan seems widely dispensable in many routine cases as it leads neither to a different operative strategy nor to an improvement of surgical results. In a few selected cases, however, operative proceeding is determined by scintigraphic results. Thus the question of the importance of scintigraphic methods for thyroid diagnostics and therapy as well as for the selection of patients for surgery cannot be answered and must be subject of a separate examination. PMID- 2272233 TI - [Invagination in childhood]. AB - This paper is a retrospective study of all children with intussusception, who were treated in the pediatric surgical clinic in the Dr. v. Hauner'sches Kinderspital of the University of Munich from 1970 to 1988. In this time we evaluated 99 cases out of 101 children. Points of interest were epidemiological data, such as sex ratio, average age, place of residence, exact documentation of the anamnesis typical of this pediatric surgical entity, of diagnosis, site of intussusception as well as of frequency of conservative barium enema reduction and surgical treatment respectively. 68 patients of these evaluated 99 cases had to be operated. As far as postoperative courses are concerned bowel obstruction occurs in 6 patients, 4 cases developed a relapse of intussusception and one child died. PMID- 2272234 TI - [Cervical catheter esophageal stoma. A technical modification of the bipolar exclusion in surgical treatment of advanced esophageal perforation]. PMID- 2272235 TI - [Thymolipoma--a rare mediastinal tumor]. PMID- 2272236 TI - [Primary extranodal pulmonary lymphoma]. PMID- 2272237 TI - [Traumatic heart dislocation. Case report]. PMID- 2272238 TI - [Traumatic myocardial infarct. A case report]. PMID- 2272239 TI - [Comment on the contribution by M. Sachs et al.: Metabolic changes and infusion therapy in ileus]. PMID- 2272240 TI - Chromosomal evolution in Callithrix emiliae. AB - We studied the karyotype of specimens of Callithrix emiliae (Callithricidae, Primates) from Rondonia, Brazil. Comparison with the karyotype of Callithrix jacchus showed that, even though these two species show many karyotypic similarities, they differ by a Robertsonian translocation, a paracentric inversion and large-scale addition of heterochromatin. The C. emiliae species appears to be in an active phase of chromosome evolution by the addition of constitutive heterochromatin. PMID- 2272241 TI - A review of techniques and results obtained in one laboratory by an integrated system of methods designed for routine clinical flow cytometric DNA analysis. AB - Establishing flow cytometric DNA analysis as a clinical routine procedure requires adequate and proven guidelines, by which the data can be obtained and interpreted to directly influence management of the individual patient with a specific neoplasm. The present paper is intended as a contribution to such guidelines, of which only fragments are available today. We have previously described a system of methods, designed for routine flow cytometric DNA analysis. In the present status report our experience, based on approximately 18,000 samples (clinical and experimental) is summarised. Sample acquisition with fine needle aspiration, storage at -80 degrees C, internal standardization by chicken (CRBC) and trout red blood cells (TRBC), staining with propidium iodide (PI), and analysis in the flow cytometer is recapitulated, with emphasis on previously unpublished aspects. The method of statistical analysis which has an integrating role is described in some detail. A lack of linearity between channel number and DNA content was determined experimentally, and the coefficient of variation (CV) was found to decrease with increasing channel number. The corrections in the algorithm of deconvolution made necessary by these findings are fundamental for estimating the end results. The zero point adjustment and procedures for changing from one batch of standards to another are described. A systematic approach to interpretation of DNA histograms is attempted and illustrated by data from clinical specimens of malignant lymphoma, breast cancer, small cell lung cancer, cancer of the oral cavity, and bladder cancer. Some problems are still unsolved and visual inspection is required to determine if the quality of the individual histogram is satisfactory. Inspection of the fluorescence/light scatter dot-plot provides additional information for the recognition of artifacts. The results stress that good quality DNA histograms with as small CVs as possible are important for interpretation of the data. It is essential that statistical methods are employed to extract the key end-point results. These are the number of subpopulations and their relative representation, and for each subpopulation the DNA index (DI) and the fractions of cells in the cell cycle phases. For the DNA data to have any rationally based impact on clinical decision making, it must be demonstrated that they have an independent prognostic value. Strategies for final evaluation are discussed. Multicenter trials on fresh material, to accrue quickly the number of patients necessary for firm conclusions, are suggested. PMID- 2272242 TI - Geometrical constraints on the shape of cultured cells. AB - Previous studies on cultured cells revealed that the values of certain shape descriptors were highly correlated despite the fact that there was little mathematical interdependence (Heckman, CA: In Advances in Cell Culture, Vol. 4, K. Maramorosch, ed, pp 85-156, 1985). The independence of such descriptors was tested by calculating the values of correlations among descriptors for a data set consisting of macroscopic objects. The descriptors were unlinked for this data set, confirming that high correlations reflected specific characteristics of cultured cells. These characteristics were identified by constructing model figures incorporating the geometrical features postulated to be responsible for each correlation. Because the position of the ellipse of concentration depended upon the form in which mass was displaced in figures, the fraction of the figure falling within the area of the ellipse (FINE) and the ratio of the ellipse area to the figure's area (ARAT) became decorrelated from each other in figures with massive projections. Further, correlations between ARAT or FINE and variables measuring cavities and inflections of the perimeter showed a complex dependence on the size, shape, and number of invaginations. Descriptors could become decorrelated due to features present in only a minority of cells of a population. Finally, cell populations that differed with respect to physiological characteristics showed no differences in the value of ARAT:FINE correlation. However, correlations between ARAT and the coefficient of variation of centroid to-perimeter distances were altered. This suggested that correlation coefficients may be themselves powerful descriptors of the shape characteristics of cell populations. PMID- 2272243 TI - Inorganic phosphors as new luminescent labels for immunocytochemistry and time resolved microscopy. AB - A new strongly luminescent marker consisting of inorganic crystals is described for time-resolved microscopy. These crystals, known as phosphors, show delayed luminescence, unlike prompt fluorescent labels such as FITC, TRITC and phycobiliproteins, and are therefore potentially suitable for time-resolved microscopy. The luminescence of these phosphors is strong and non-fading in comparison to FITC/TRITC, and not significantly influenced by pH or temperature. The phosphor yttriumoxisulfide activated with europium emits maximally at 620 nm with a typical half life-time of approximately 700 musec, upon excitation with near ultraviolet light (360 nm). Phosphors for immunocytochemical staining were made by ball milling and were stabilized in suspension with polycarboxylic acids. Proteins such as avidin, protein A or immunoglobulins were allowed to adsorb to the surface of the phosphors. The immunocytochemical properties of the conjugates were evaluated in a model system of latex beads with defined surface antigens and in a cellular system containing fixed human lymphocytes or erythrocytes. Specific cytochemical staining was observed in suspension as well as on glass slides. A specially constructed time-resolved microscope was used to suppress the fast decaying fluorescence, thereby permitting visualization of the specific, slowly decaying luminescence of the phosphor label without the necessity of integration. Finally, the use of multiple phosphors with different kinetic and spectral characteristics for multiparameter studies is indicated. PMID- 2272244 TI - The determination of growth rates of individual colonies in agarose using high resolution automated image analysis. AB - This paper describes the evaluation of a colony formation assay using automated image analysis, which permits the tracking of growth at the individual colony level, such that a growth rate can be estimated for each colony followed. In principle, this will permit quantitative characterization of cellular heterogeneity in growth rate and cellular heterogeneity in response to proliferation-modifying agents. In addition, we have demonstrated the possibility of using correlative microscopy to relate growth rate to other parameters, using metabolic viability as an example. This should be useful for determining cellular characteristics associated with proliferative behavior and response to proliferation-modifying agents. PMID- 2272245 TI - Eight-parameter PC-AT based flow cytometric data system. AB - An 8-parameter flow cytometric data system is described using an IBM-AT compatible personal computer (PC) and a commercial analog to digital conversion (ADC) board. A dedicated pulse processing interface adapts the flow cytometric pulses to the ADC board and controls the number of parameters to be taken up and the trigger conditions. The trigger thresholds are automatically held at a level immediately above the noise level. For the timing of kinetic measurements a linear voltage ramp of adjustable rise time is available. A built-in precision voltage source can be used for an overall calibration. The data system is operated by software written in assembly language. Data may be collected and processed in 1-8-parameter listmode or 1-3-parameter histogram mode. Functions are available for graphical color displays, numerical integration, multiparameter gating, and printing. PMID- 2272246 TI - Flow cytometric analysis of G1- and G2/M-phase subpopulations in mammalian cell nuclei using side scatter and DNA content measurements. AB - Several subcompartments of the cell cycle in addition to the G1-, S-, and G2 phases usually observed were identified by simultaneous flow cytometric measurements of ethidium bromide fluorescence and side scatter intensity of cell nuclei. Metaphase cells and very early G1-phase cells (G1A) with low side scatter intensities were discriminated from interphase cells with high side scatter intensities. The reason for the various side scatter intensities was found to be the different structure of metaphase cells and early G1-phase cells due to chromatin condensation as shown by sorting of the respective cell nuclei. The G1A phase could further be subdivided into two compartments with very low side scatter (G1A1) and intermediate side scatter (G1A2) intensities. Using partially synchronized cells the duration of these subcompartments of the G1-phase could be estimated. The durations of G1A1- and G1A2-phases were found to be about 10 min and 20 min, respectively, compared to the total duration of the G1-phase of about 3 h. Additional flow cytometric measurements of side scatter intensities of cell nuclei provide therefore further information on subcompartments of the G1- and G2/M-phases. PMID- 2272247 TI - Flow cytometric detection of ornithine decarboxylase activity in epidermal cell subpopulations. AB - Using flow cytometry in combination with membrane permeabilization techniques to enhance binding of antibodies with immunoreactive protein within the cytoplasm, we have developed a method to examine the ornithine decarboxylase (ODC) activity present within subpopulations of epidermal cells following acute and chronic exposure to the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). The method described has the sensitivity to detect basal levels of ODC as well as increases in ODC at early time points following treatment with TPA and has the additional advantage of allowing subpopulation identification and characterization. PMID- 2272248 TI - Increasing sensitivity of the Ortho analytical cytofluorograph by modifying the fluid system. AB - By adding Teflon tubing to the effluent line of the Ortho 50H analytical cytofluorograph, we were able to increase the sensitivity of fluorescence and scatter detection threefold without compromising resolution. By increasing sheath backpressure (resistance), the additional tubing increases particle residence time within the detection area and thereby increases the total photon emission density per particle. In addition, the longer, wider tubing dampens the stream destabilizing effects of minor obstructions in or movement of the effluent line. This increase in sensitivity and stability is desirable in applications requiring detection of particles exhibiting low-level fluorescence. PMID- 2272249 TI - Detection of cells resistant to alkylating agents by flow cytometric analysis of DNA damage. AB - DNA damage was measured by flow cytometric analysis of cells sensitive and resistant to alkylating agents. Human ovarian carcinoma cell line A2780 and a subline which is 7 times more resistant to L-phenylalanine mustard (L-PAM) were treated with the drug, fixed, and stained with monoclonal antibody (MOAB) F7-26 which detects single-stranded regions in alkylated DNA. Mean fluorescent intensity was measured on a flow cytometer. Cells were heated before staining to amplify single-strandedness in alkylated DNA. Significantly larger amount of MOAB was bound to DNA in sensitive than in resistant cells. Fluorescence increased by 80 channels per micrograms L-PAM insensitive cells and only by 17 channels in resistant cells. Sensitive and resistant cells were treated with L-PAM, mixed in different proportions, and stained with MOAB. Populations of sensitive and resistant cells were clearly separated on fluorescence histograms by more than a decade difference in fluorescence intensity. Presence of 2-5% resistant cells was detected among sensitive cells as a separate cell subset. We conclude that staining with MOAB F7-26 can be used as an indicator of cell sensitivity or resistance to alkylating agents. Detection of minor subsets of resistant cells in heterogeneous populations by FCM analysis may be useful for monitoring emerging drug resistance. PMID- 2272250 TI - Cytophotometric analysis of cervical intraepithelial neoplasia grade III, with and without synchronous invasive squamous cell carcinoma. AB - Cytophotometric analysis was performed in nuclei retrieved from paraffin-embedded cervical tissue from 57 cases of CIN III. CIN III lesions of patients without invasive squamous cell carcinoma (N = 37) were regarded to represent a mixture of progressive and nonprogressive lesions. The CIN III lesions of patients with a synchronous invasive squamous cell carcinoma (N = 20) were regarded as representing truly progressive precursor lesions (CIN.INV). Twenty-one photometric features describing geometrical, density, and texture characteristics were extracted from the digitized nuclear images. Statistical analysis of cytophotometric data indicated significant differences between the group of CIN III lesions and CIN.INV lesions. A cluster analysis, using one co-occurrency texture feature (S-HOMOG), one density feature (S-DI), and two geometrical features (S-AREA and M-CIRC), showed that two clusters (C1 and C2) were present in the total group of CIN III and CIN.INV lesions. The vast majority of CIN.INV lesions was member of one and the same cluster C1. The CIN III group appeared to consist of a mixture of two clusters, 54% C1 and 46% C2 lesions. Of patients 45 years or younger, the majority (62%) of CIN III lesions had feature values, corresponding with those of cluster C1, and as such possibly with a potentially progressive course. In patients older than 45 years the percentage of CIN III lesions with C1 feature values was 27%. PMID- 2272251 TI - Flow cytometric evaluation of nitro blue tetrazolium (NBT) reduction in human polymorphonuclear leukocytes. AB - Oxidative metabolic burst of activated human polymorphonuclear leukocytes (PMN) is most commonly investigated in clinical practice by evaluating nitroblue tetrazolium (NBT) reduction at the single cell level. Reduced NBT precipitates where the redox reaction has taken place and can be visualized as PMN-associated dark blue granules of formazan in light microscopy. Although widely used and not technically demanding, this method remains subjective and labor intensive, especially when large numbers of samples need to be investigated. We developed a new flow cytometry technique in which PMN membrane was rendered fluorescent by a short incubation with fluorescein-conjugated Concanavalin A. PMN were then incubated with NBT and increasing doses of a suitable stimulus, such as phorbol myristate acetate (PMA). Formazan has a distinct peak of absorption at 520 nm that represents the peak of emission of fluorescein. As a consequence, formazan quenches the PMN-associated fluorescence. Data show that a dose-dependent reduction of fluorescence can be obtained using graded amounts of PMA in normal PMN cultures. PMN-associated fluorescence remains unchanged in control patients with chronic granulomatous (CGD) disease, a disorder characterized by a selective impairment of PMN oxidative metabolism. Electronic cell size increases upon PMA incubation in normal PMN, irrespective of the presence of NBT. Conversely, forward light scatter intensity decreases in the presence, but not in the absence, of NBT indicating that the phenomenon is due to the capacity of formazan to absorb/scatter the incident light. The present method for easily detecting NBT reducing activity at single cell level by flow cytometry makes use of commonly available, inexpensive reagents and standard instrumentation. It could become a useful test for clinical purposes. PMID- 2272252 TI - A method for calibration of flow cytometric wavelength shift fluorescence measurements. AB - Recently, new fluorescent dyes have been introduced into flow cytometry which alter their spectral characteristics when changes occur in certain cell features, e.g., intracellular pH or calcium ion concentration. Such changes may be determined by measuring the fluorescence intensity ratio in two different wavelength ranges (5). Here a new method is described, which simplifies the use of steadily flowing fluids for calibration. The pulse electronics of a flow cytometer cannot process the static fluorescence signals of a streaming fluid. If, however, the exciting or emitted fluorescence light of a calibration fluid is made pulsating, the flow cytometer electronics can evaluate those pulses. The new calibration procedure uses measurement of two wavelength windows shown in a two parameter display to generate an absolute calibration scale. Measurement of the spectral shift in calibration fluids under identical instrumental settings provides absolute values that measurements of intracellular concentrations can be referred to. PMID- 2272253 TI - Macintosh graphics for the EPICS flow cytometer user. AB - Graphic options for the EPICS flow cytometer user have been restricted in the past to software written specifically for the analysis and graphics of flow cytometric data. The software is limited to only a few graphic presentation styles. The technique described will allow the EPICS user to translate histogram files into text files that can be used in an alternative computer format. PMID- 2272254 TI - Personal computer interface and software for the ZONAX microscope attachment controller. AB - We describe the hardware and software of a general-purpose interface that permits a personal computer (PC) running MS-DOS to control cytometric devices, e.g., a scanning stage, shutters, and focus motor attached to a microscope. This note explains how to use the interface to convert the ZONAX microscope attachment controller from 8080-based hardware control to PC-based control. PMID- 2272255 TI - Improved method for measuring intracellular Ca++ with fluo-3. AB - The accuracy of flow cytometric measurement of intracellular calcium with fluo-3 is compromised by variation in basal fluorescence intensity due to heterogeneity in dye uptake or compartmentalization. We have loaded cells simultaneously with fluo-3 and SNARF-1. When SNARF-1 fluorescence is collected at approximately 600 nm, its intensity does not change upon cell activation. Furthermore, fluo-3 and SNARF-1 fluorescence signals exhibit a linear relationship. The ratio of fluo-3 to SNARF-1 eliminates a significant proportion of variation in fluorescence intensity caused by variation in fluo-3 uptake and thus can be used as a sensitive parameter for measuring changes in [Ca2+]i. PMID- 2272256 TI - [Use of polymerase chain reaction (PCR) to detect monoclonality of B lymphoproliferative disorders at DNA level]. AB - A technique has been developed using PCR to detect monoclonality of B lymphoproliferative disorders. DNA was extracted from the tissue, blood and paraffin embedded sections by biochemical means or boiling. Forty cases of B-non Hodgkin's lymphoma (NHL), 15 cases of T-NHL, 8 cases of chronic lymphocytic leukemia, 17 cases of reactive lymphadenopathy and 12 cases of various non lymphatic tumor were examined. Monoclonality of B-lymphocytes was detected in 86 92% of cases with B-lymphoproliferative diseases, but none in T-NHL, reactive disorders and non-lymphatic tumors. This technique provides a new molecular biologic method to diagnose malignant B-lymphoproliferative disorders. It may be useful in Ig gene rearrangement study, differential diagnosis and retrospective investigation of lymphoproliferative disorders. PMID- 2272257 TI - [Synergistic antitumor activity of human breast cancer immunotoxins]. AB - Three anti-breast carcinoma monoclonal antibodies 317G5, 260F9 and 741F8 linked to ricin A chain (rRTA) were selected for the present investigation. Attempts were made to understand the relative efficiency of these immunotoxins in relation to: a) binding, b) internalization, and c) clonogenic suppression of breast cancer cells in vitro. The results indicated that 317G5-rRTA combined with 260F9 rRTA had synergistic antitumor activity against SKBr3 breast carcinoma cell line. Individually, 10 micrograms/ml 260F9-rRTA or 317 G5-rRTA alone could only eliminate 2-3 logs of clonogenic SKBr3 cells. When used in combination, 260F9 rRTA and 317G5-rRTA, 1 microgram/ml each, could kill 4 logs of clonogenic tumor cells. The mechanism of the synergistic action is discussed. PMID- 2272258 TI - [Anti-human lung giant cell cancer (PG) effect of human LAK cells in vitro and in nude mice]. AB - Human LAK cells were prepared by culturing normal human peripheral blood mononuclear cells (PBMC) with or without rIL-2 and assayed for T cell surface markers as well as anti-tumor activity against PG in vitro and in nude mice. Although the percentages of T3, T4 and T8 positive cells in rIL-2-activated cells did not differ significantly from those of control cells in vitro, the former showed stronger cytotoxicity than control cells to PG tumor cells in vitro. In vivo, LAK cells completely inhibited the growth of PG tumor in nude mice, whereas PBMC control cells were of no effect. The anti-tumor effect of human LAK cells in nude mice may offer a useful model to study the role of human LAK cells against human tumor in vivo. PMID- 2272259 TI - [Synergistic killing effect of hyperthermia and radiation on human cecum adenocarcinoma cell line in vitro]. AB - Synergistic killing effect of hyperthermia and radiation on human cecum adenocarcinoma cell line (HCe-8693) was studied as to cell growth curve, mitotic index, concentrations of potassium and beta 2-microglobulin, CEA content and cell morphology under light and electron microscopes. The cultured cells were randomly divided into 5 groups: control (C), radiation alone (R), hyperthermia alone (H), radiation followed by hyperthermia (RH), hyperthermia followed by radiation (HR). The preliminary results showed that (1) the killing effect of radiation alone was mild, (2) hyperthermia alone had more marked killing effect than radiation alone, but viable HCe-8693 cells were still able to grow, (3) combination of hyperthermia and radiation showed synergistic effect which was more pronounced in RH than HR. PMID- 2272260 TI - [Electron microscopic observation of differentiation of leukemic cell clone after CFU-Mix culture]. AB - By scanning and transmission electron microscopy, leukemic cells were observed after CFU-Mix culture. Even though granulocytic growth factor, erythropoietin and lymphocytic growth factor were added in vitro, acute leukemic cells still showed defective differentiation and maturation. These were characterized by abnormal colony which consisted of smooth cells, bizarre shape, nuclear-cytoplasmic asynchrony in development, and appearance of nuclear bleb. However, chronic myelogenous leukemic cells were more mature than the acute ones, manifesting in normal colony with finger-like projections and ruffled membrane. Macrophages and eosinophils could be observed. It is suggested that there is a difference in differentiation between acute and chronic leukemic cells. PMID- 2272261 TI - [Histologic grade, DNA content and image analysis in soft tissue tumors]. AB - Flow cytometry and image analysis technique were used to quantitate the nuclei of various soft tissue tumors. A single representing section from soft tissue sarcoma was used for histologic grading. Histologic and cytometric comparative analyses showed that all 21 benign tumors were diploid. Among 62 cases of soft tissue sarcoma, 45 (73%) were aneuploid. There was a significant difference in the nuclear area between benign and malignant tumors (P less than 0.01), diploid and aneuploid tumors (P less than 0.05). The two new techniques are valuable in cellular quantitative measurement for soft tissue tumors. PMID- 2272262 TI - [Flow cytometry in exfoliative cytology of malignant tumor]. AB - Exfoliative cells from 170 cases of malignant tumor and 70 cases of normal tissue were studied by flow cytometry. The results showed that 155/170 (91.2%) cases were positive and 15/170 (8.8%) were false-negative; 4/70 (6.0%) cases were false positive. The authors consider that flow cytometry has achieved a diagnostic accuracy comparable to the conventional cytology. Flow cytometry is a useful supplementary method in the diagnosis of tumors. PMID- 2272263 TI - [Effects of nitrosamine on in vitro cultured human esophageal epithelial cells]. AB - Explant-cell culture system of human esophageal mucosa was used for studying the in vitro biological effects of nitrosamines, the major suspected causative agents of esophageal cancer in Linxian County, on esophageal epithelial cells. These carcinogens showed a cytotoxic effect in most of the 10 cases tested. A dose response relationship of cell number reduction was observed at certain dose range. However, the effect of these carcinogens on cellular DNA synthesis was not always suppressive. At certain concentrations, nitrosamines mainly stimulated DNA synthesis in all of the 4 cases studied. The cells treated by these carcinogens seemed to have an enhanced growth potential during subculturing. PMID- 2272264 TI - [Expression of interleukin 2(IL-2) receptor and proliferative response to rIL-2 of peripheral blood mononuclear cells (PBMC) in patients with malignant diseases]. AB - Expression of IL-2 receptor and proliferative response to rIL-2 of PBMC were studied in 48 patients with malignant diseases and in 50 normal subjects. Having been activated by PHA, PBMC from cancer patients had about the same percentage of Tac positive cells as compared with the normal subjects. However, resting and Con A-activated PBMC showed a significantly weaker proliferative response to rIL-2 in cancer patients than in normal subjects (P less than 0.001-0.005). The decrease in PBMC proliferative response to rIL-2 in patients with malignant diseases might be due to a defect in the formation of high affinity IL-2 receptors. PMID- 2272265 TI - [Modified radical mastectomy--an analysis of 217 cases]. AB - Modified radical mastectomy (MRM) was performed in two hundred and seventeen patients with operable breast cancer during 1972-1982. Having been followed for 5 to 10 years, the results were compared with those of radical mastectomy (RM) during the same period. There was no significant difference in 5 and 10 year survival rates between the two groups. MRM had the advantages of insignificant deformity, better function and easy breast reconstruction in comparison with RM. The authors believe that MRM should be recommended as the treatment of choice for breast cancer. PMID- 2272266 TI - [Clinical and histological study on breast cancer treated by preoperative mitoxantrone]. AB - Fifteen patients with breast cancer treated with mitoxantrone preoperatively from December 1986 to June 1983 were evaluated as to treatment validity and histological response. It was shown that the mass in the breast became reduced 7 days after the start of treatment. Intact border and halo were formed around the mass and echo level inside the focus was increased even replacing all hypoecho areas by B-ultrasound. Microscopically, cell karyopyknosis, chromosome breaking plus karyorrhexis, mitochondrial destruction, vacuolization, reactive regeneration of a few capillaries and connective tissues were observed in the resected samples. Preoperative treatment with mitoxantrone helps prevent local recurrence and metastasis after tumor resection. PMID- 2272267 TI - [Preliminary clinical application of new bone marrow imaging agent 99mTc polyphase liposome in malignant lymphoma]. AB - Bone marrow (BM) imaging with 99mTc-polyphase liposome in 30 malignant lymphoma patients demonstrated that central BM hypoplasia accounted for 90% (28/30) and peripheral BM hypoplasia 20% (6/30) with peripheral BM expansion of 80% (23/30). Focal BM lesion was shown in 7 patients which conformed with the results of bone imaging and X-ray film. The uptake index of BM in patients treated with chemotherapy was low as compared to that in patients treated with radiotherapy (P less than 0.05). Although BM suppression by chemotherapy was more severe than by radiotherapy, BM function essentially recovered 1 month after cessation of chemotherapy, on the other hand, while central BM suppression by radiotherapy was mild, it lasted for longer periods of time. Peripheral BM suppression by radiotherapy was both shorter in duration and milder in severity in comparison with central BM suppression. BM imaging is valuable for the understanding of BM function, ascertainment of the appropriate interval between treatments and early detection of local BM involvement. PMID- 2272268 TI - [Postradiation cancer of oral and maxillofacial regions]. AB - Twenty-two patients with postradiation cancer of oral and maxillofacial regions treated in our hospital from 1969 to 1985 are reported. Of them, 3 patients had double postradiation cancers. The shortest interval between the two primary cancers was 3 years, the longest was 32 years with a median of 9 years. Of 15 patients treated with 60Co, 9 patients developed cancers and 6 sarcomas. In 4 patients treated with deep X-ray, cancers developed in 3 and sarcoma in one. Three patients were treated with 60Co, deep X-ray and radium implantation, all of them developed cancers. Radiation dose ranged from 3000 to 10,000 cGy but in most of the patients it was 7000-8000 cGy. In 19/22 patients the postradiation cancers were resected, giving 3 and 5 year survival rates of 50% and 23%. Only 1 patient survived for 14 years. Three patients treated by non-operative methods all died within 1-2 years. More aggressive treatments in patients with postradiation cancer are therefore indicated. PMID- 2272269 TI - [The selection of treatment for giant-cell tumor of bone]. AB - Eighty-two patients with giant-cell tumor of the bone were operated with 4 different methods depending on the site of tumor, extent of local invasion and degree of malignancy. Curettage plus filling operation was performed for Grade I tumors and localized lesions. Resection of the tumor segment and replacement of the joint with allograft or artificial joint were done for Grade II tumors involving the joint but with clear borders. The indications of amputation were Grade III tumors, frequent recurrence and malignant change. Local curettage plus radiotherapy was undertaken in tumors that could hardly be completely curetted, such as tumors in the sacrum and spine. The results showed that the first method gave a high recurrence rate; the second method was the best; the third was worse due to conservativeness of amputation; the fourth method had the poorest prognosis owing to incomplete removal of the tumor. PMID- 2272270 TI - [Distribution and depth of internal mammary lymph nodes in breast cancer]. AB - Lymphoscintigraphy was performed in 50 cases of breast cancer using 99mTc-colloid as a tracer. The results indicated that 277 lymph nodes, 128 on the right side and 149 on the left, were imaged. Most of the lymph nodes were located in the second and third intercostal spaces. The mean distance between these lymph nodes and mid line was 1.93 +/- 1.05 cm-2.70 +/- 0.93 cm. The mean depth was 2.42 +/- 0.52 cm-3.07 +/- 0.72 cm. It was over 4.0 cm in isolated cases. The lymph nodes which were not showed after repeated examination could have been involved by the cancer. Radionuclide lymphoscintigraphy, being safe, easily repeated and having low radiation dose and good image, is very useful for radiotherapy. PMID- 2272271 TI - [Prognostic factors of extranodal non-Hodgkin's lymphoma--an analysis of 62 cases]. AB - Sixty two cases of extranodal non-Hodgkin's lymphoma (NHL) treated in our hospital from June 1979 to June 1986 are reported. The ratio of male to female was 2.44:1. The ages ranged from 7 to 65 with a peak age of 30-49 years. According to the criteria of Chengdu conference (1985), these 62 cases were categorized into 4 types: lowly malignant (11), moderately malignant (26), highly malignant (21) and unclassified (4). According to Ann Arbor Staging System (1971), there were 16 patients in Stage I, 23 in Stage II, 16 in Stage III and 7 in Stage IV, of which there were 10 cases with B symptoms. All patients were followed until September 1988. The survival rate was calculated according to the life statistical table. The results showed that patients in Stages I and II with low malignant type in pathology and without B symptoms had a favorable prognosis, whereas those with a mass originating from the Waldeyer's ring, cervical lymph node over 5 cm in diameter and lower neck and/or supraclavicular regions or bilateral cervical lymph node involvement had a poor prognosis. PMID- 2272272 TI - [Primary plasma cell leukemia--a comprehensive analysis of 44 cases]. AB - Four cases of primary plasma cell leukemia (PPCL) admitted to our hospital from 1959 to 1987 are reported with a review on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) seen in our hospital, the following features were observed in PPCL: (1) The age was younger with a mean of 45.2 years, 34.1% of the patients were under 40 years. (2) Onset was abrupt. Duration from onset to diagnosis was 2 months or less in 77% patients but never beyond 6 months. (3) 81.8% patients had liver enlargement, 59.1% splenomegaly and 61.4% sternum tenderness. (4) All patients showed marked anemia with an average hemoglobin of 65 g/L. BPC count was less than 100 x 10(9)/L in 76% patients and WBC was more than 10 x 10(9)/L in 77%. (5) Plasma cell number in the marrow was markedly increased with an average of 69%, of which the blast cells and immature forms were predominant. (6) No destruction of bones was shown on X-ray film in 68.3% patients. (7) The response to chemotherapy was poor with a total response rate of 18% and a mean survival of 2 months. All the above-mentioned clinical features were significantly different from those of MM. In addition, these two diseases were also different in cytology, cytogenetics and ultrastructure. Therefore, PPCL should be considered as a special type of acute leukemia distinct from MM. High dose of alkylating agents in combination with autologous bone marrow transplantation might improve the prognosis. PMID- 2272273 TI - [The immunoelectron microscopic localization of histone-like proteins in the chromatin of luminescent bacteria]. PMID- 2272274 TI - [The differential effect of the antimutagenic action of interferons in relation to primary DNA damages: the genetic risk of 8-methoxypsoralen monoadducts is greater than that of interstrand DNA crosslinks]. PMID- 2272275 TI - [Mutant Saccharomyces cerevisiae yeasts with an increased level of heterologous protein secretion]. PMID- 2272276 TI - [The inactivation of the AIDS virus]. PMID- 2272277 TI - [Vitamin E regulation of the topography of the cholinoceptors in mollusk neurons]. PMID- 2272278 TI - [Nonspecific resistance and the DNA content in the genome of amphibians]. PMID- 2272279 TI - [The 5'-terminal untranslated sequence of the genomic RNA in the potato X virus produces efficient enhancement of the translation of a foreign gene]. PMID- 2272280 TI - [The effect of radiation in the magnesium lines on the reverse transcription process]. PMID- 2272281 TI - [The structure-function relationships in alpha-interferons. A study of the antiviral activity of mutant forms of human alpha 2-interferon]. PMID- 2272282 TI - [The DNA regions of hepatitis B virus homologous to the yeast replication enhancer]. PMID- 2272283 TI - [The mechanism of the interaction of platinum preparations having antitumor action with supramolecular tubulin complexes--microtubules]. PMID- 2272284 TI - [The specific interaction of soluble nuclear proteins with the cloned fragments of DNA permanently attached to the nuclear skeleton]. PMID- 2272285 TI - Cytochrome P450IIE1: roles in nitrosamine metabolism and mechanisms of regulation. PMID- 2272286 TI - The metabolism and mode of action of gentian violet. AB - Gentian violet has been used in medicine for almost 100 years: as an antiseptic for external use, as an antihelminthic agent by oral administration, and more recently, as a blood additive to prevent transmission of Chagas' disease. To date, no serious side effects have been reported when used externally. However, oral administration can cause gastrointestinal irritation, and intravenous injection can cause depression in the white blood cell count. Surprisingly, no acute toxic side effects were reported after administration of large amounts of gentian violet-treated blood. No studies have been done on long-term effects (chronic toxicity, carcinogenicity) of gentian violet-treated blood either in humans or in laboratory animals. Gentian violet is a mutagen, a mitotic poison, and a clastogen. The carcinogenic effects of gentian violet in rodents have been reported recently. In addition, a number of triphenylmethane-classed dyes, of which gentian violet is a member, have been recognized as animal and human carcinogens. A photodynamic action of gentian violet, apparently mediated by a free-radical mechanism, has been described in bacteria and in T. cruzi. However, the main target of gentian violet toxicity in the dark is the mitochondrion. Gentian violet is actively demethylated by liver microsomes from different animals and is reduced to leucogentian violet by intestinal microflora. Although the first process may represent a detoxication reaction, the second pathway may have toxicological significance because the completely demethylated derivative leucopararosaniline has been demonstrated to be carcinogenic in rats. A free radical derivative of gentian violet is also formed by the action of rat liver microsomes, but whether this radical is involved in the cytotoxic effects of gentian violet in mammalian cells remains to be elucidated. Other pathways of gentian violet metabolism have recently been investigated that involve its oxidative N-demethylation by peroxidases. The N-demethylation of gentian violet by prostaglandin synthetase deserves further study. In this regard, the PGS system is being studied as an alternative activating pathway in xenobiotic metabolism because some carcinogenic intermediates can be formed during this cooxidation reaction. PMID- 2272287 TI - Interspecies metabolism and pharmacokinetic scaling of theophylline disposition. PMID- 2272288 TI - Metabolism of nitro-polycyclic aromatic hydrocarbons. PMID- 2272289 TI - Biphasic mortality response of chipmunks in the wild to single doses of ionizing radiation: toxicity and longevity hormesis. AB - Based on survivalship data from Tryon and Snyder, wild chipmunks (Tamias striatus), captured, exposed to single doses of either 200 or 400 rad ionizing radiation, and subsequently returned to their natural habitat, exhibited a biphasic response in age-specific mortality rate (omega x). On the one hand, a residuum of unrepaired toxicity (injury) appeared to persist and manifest itself throughout life (enhancement of omega x values). A second response, termed longevity hormesis (of unknown mechanism), was also observed. This phenomenon initially reduced omega x values but was reversible. A relatively simple mathematical model characterizing differences in mortality experience between control and irradiated populations was formulated and tested. Although there were some shortcomings, the model characterized the data reasonably well. PMID- 2272290 TI - [Atypical mycobacterium infections]. AB - In response to an overview in Dermatosen 32, 195 (1984), here is given an update based on citations of newer works in this field. The growing importance of atypical mycobacteria is supported by the increasing cases of such infections in AIDS-patients. PMID- 2272291 TI - Prophylactic endoscopic sclerotherapy of esophageal varices--a prospective randomized trial. AB - Sixty-three patients with degree III or IV esophageal varices and the so-called red color sign, but without previous bleeding were randomly assigned to either prophylactic sclerotherapy (PST) (n = 30) or to a control group (n = 33). In 58 cases the portal hypertension was caused by liver cirrhosis (40% alcoholics). The two groups were comparable with respect to demographic data and endoscopic appearance, causes and severity of liver damage. Sclerotherapy was performed as combined intra-and paravariceal injections of 2 or 3% polidocanol. All patients, both in the treatment and in the control groups, who bled from varices after randomization, received sclerotherapy until the varices were eradicated, and remained in their groups. After a mean follow-up of 44.5 months, the bleeding rate in the PST group was significantly lower (30% vs 75%, p less than 0.01). The difference became significant from the second year onward. Fourteen patients of the PST group and 19 of the controls died (4 and 14, respectively, p less than 0.05 as a result of the bleeding). Life table analysis (Kaplan-Meier) revealed no differences in survival between the two groups. At the present time PST cannot yet be recommended as a method for clinical routine use. PMID- 2272292 TI - Balloon dilatation of anastomotic intestinal stenoses: long-term results. AB - Since 1983 we have treated 59 consecutive patients with anastomotic intestinal strictures. In 43 cases the stenosis was located in the esophagus, and in 16 cases in the colon. The balloon catheter was positioned under fluoroscopic and endoscopic control. The number of dilatations required by each patient ranged from one to five, with 47% of our patients receiving only one session, and 23% two sessions. We had no initial treatment failures. We observed stricture relapse in 10.1% of our cases, occurring within two to five months. In these patients repeat dilatation was 100% successful. We had no significant complications. All the patients with esophageal stricture were able to eat solid food after dilatation. Long-term results and relapse-free intervals have been assessed on a clinical basis with a mean follow-up of 26.5 months. Balloon dilatation would seem a safe and reliable method of treating anastomotic strictures, with special emphasis on stenosis with a small diameter, and tortuosity of the gut. PMID- 2272293 TI - Percutaneous transhepatic gallstone dissolution with methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies. AB - In a total of 117 successfully punctured patients with gallbladder stones that were to be treated with methyl tert-butyl ether, 11 showed shell-like structured concrements on the CT scan. In 2 patients, pigment stones and very old concrements were suspected. In these 13 patients solitary stones dissolved in 2.9 hours, multiple stones in 10.8 hours, which corresponds to the treatment time of the total group. In 4 patients we diagnosed cholesterol stones, but dissolution was very slow, suggesting that the stones were covered with pigment. In 21 patients we found marked gallbladder anomalies, such as extreme septation, two chamber gallbladders, gallbladder diverticula with a wedged stone, or gallbladders in which the fundus was positioned cranially. In these patients puncture time was prolonged by 25%. However, since in all patients the stones dissolved in the same time as in the total group (solitary stones; 3.1 hours: multiple stones: 10.4 hours) and since in 33% there was also sludge in the gallbladder, shape variants of the gallbladder obviously have no influence on the stone type. Whether they induce recurrent stones more often than normal gallbladders cannot be assessed at present. Shape variants of the gallbladder and layered stones on CT scan, however, do not represent a contraindication to MTBE therapy. PMID- 2272294 TI - Endoscopic ultrasound Doppler probes for velocity measurements in vessels in the upper gastrointestinal tract using a multifrequency pulsed Doppler meter. AB - To quantify flow velocity in vascular structures in the upper gastrointestinal tract, prototype ultrasound Doppler transducers having frequencies of 5 and 10 MHz were designed. Connected to an advanced pulse ultrasound Doppler meter via an isolation transformer for patient safety, these transducers enabled the recording of flow velocity in vessels within an surrounding the wall of the GI tract. This set up improves the endoscopic ultrasound Doppler method by extending the measurable depth-range by using two frequencies, permitting independent selection of measuring depth and sample volume length, and giving an output format which includes full spectral analysis, simultaneous ECG and capabilities of displaying two additional signals. PMID- 2272295 TI - A new technique for replacing an obstructed biliary endoprosthesis. AB - We report on a new method of stent exchange using a threaded device that enables removal of the clogged stent while simultaneously maintaining the original pathway without withdrawing the endoscope. With this method stent replacement has become more reliable, safer, simpler and quicker. This technique is also suitable for removal of stents dislodged inside the duct. PMID- 2272296 TI - Bronchoscopic and cytopathological findings of tracheobronchial involvement in esophageal carcinoma. AB - To evaluate the usefulness of bronchoscopic and cytopathologic examinations for tracheobronchial involvement of esophageal carcinoma, we reviewed 14 cases of esophageal carcinoma suspected of tracheobronchial invasion. Two cases underwent bronchoscopy for postoperative respiratory symptoms, and both revealed endotracheal tumor growth and proved positive at brush cytology and biopsy. Among nine cases submitted to preoperative examination, bronchoscopy showed only protrusion in four cases, and redness with mucosal protrusion in five cases. Two of the latter evidenced cancer cells on brushing specimen, and their prognosis was poor. The remaining three cases underwent bronchoscopy for preoperative severe respiratory symptoms. Tumor growth was noted in two of them, and cytology or biopsy was positive. We conclude that bronchoscopy for tracheobronchial involvement of esophageal carcinoma plays a major role in the diagnosis of extra esophageal extension. Because of the anatomical situation, biopsy is sometimes difficult. Brush cytology is important in the case of mucosal protrusion and redness. PMID- 2272297 TI - Endoscopic hemostasis of esophageal and gastric variceal bleeding with Histoacryl. AB - Endoscopic injection of the tissue adhesive n-butyl-2-cyano-acrylate (Histoacryl) has been tried for esophageal or fundic variceal bleeding in 23 patients. Definitive hemostasis was achieved in 22 with a single injection of Histoacryl. Throughout the entire hospitalization period, which was completed with at least two weekly sessions of conventional sclerotherapy, only one recurrent bleeding was recorded. Four patients died of hepatic decompensation. It is suggested that Cyanoacrylate could overcome some of the shortcomings of conventional sclerotherapy such as early recurrent hemorrhage and bleeding from fundic varices. PMID- 2272298 TI - Extensive necrosis of gastric mucosa following injection therapy of bleeding peptic ulcer. PMID- 2272299 TI - Gastric necrosis: a complication of endoscopic sclerosis for bleeding peptic ulcer. PMID- 2272300 TI - Choledochal-wirsungian fistula. PMID- 2272301 TI - Transgastric perforation of a PEG and successful endoscopic management of the complication using the fibrin sealing technique. PMID- 2272302 TI - Symposium on risk factors and mechanisms in carcinogenesis. June 26-28, 1989, Wurzburg, West Germany. Proceedings. PMID- 2272303 TI - A mechanism of haloalkene-induced renal carcinogenesis. AB - Several halogenated alkenes are nephrotoxic; some others induce renal tubular adenocarcinomas in rodents after lifelong administration. A bioactivation mechanism accounting for the organ-selective tumor induction has been elucidated: conjugation of the parent compounds with glutathione (GSH), catalyzed by hepatic GSH S-transferases, results in the formation of haloalkyl and halovinyl glutathione S-conjugates. Formation of S-conjugates (identified by NMR and mass spectrometry) could be demonstrated with trichloroethene, tetrachloroethene, hexachlorobutadiene, perfluoropropene, trichlorotrifluoropropene, and dichloroacetylene in incubations with rat liver microsomes and in the isolated perfused rat liver. The GSH conjugates formed are eliminated from the rat liver with the bile and may be translocated to the kidney, intact or after metabolism to the corresponding cysteine S-conjugates that are metabolized in the kidney by renal tubular cysteine conjugate beta-lyase (beta-lyase) to reactive intermediates, most likely thioacylchlorides and thioketenes. Interaction of these potent electrophiles with DNA [demonstrated for intermediates formed from S (1,2,3,4,4-pentachlorobutadienyl)-L-cysteine] causes mutagenicity in bacteria, genotoxicity in cultured renal cells, and cytotoxicity in kidney cells. As an alternative to beta-lyase-catalyzed cleavage, the cysteine S-conjugates may be acetylated to the corresponding mercapturic acids, which have been identified in urine. The ability of the kidney to concentrate GSH and cysteine S-conjugates and the intensive metabolism of GSH S-conjugates to cysteine S-conjugates in this organ are evidently responsible for the organotropic carcinogenicity. PMID- 2272304 TI - Identification of ultimate DNA damaging oxygen species. AB - DNA damage induced by various reactive oxygen species can be characterized using a set of repair endonucleases with defined substrate specificities. DNA damage profiles thus obtained in a cell-free system can be compared with those observed in cellular DNA. Using this approach, we have demonstrated that an illumination of Salmonella typhimurium cells with visible light in the presence of methylene blue gives rise to a DNA damage profile very similar to that of singlet oxygen in a cell-free system. Therefore, the genotoxicity observed under these conditions most probably is attributable to the direct action of this species. The damage consists mainly of base modifications that are subject to repair by uvrABC independent pathways. Revertant frequencies observed in parallel in the strains TA100 and TA2638 indicate a pronounced mutagenicity of the lesions induced. Exposure of Salmonella typhimurium to tert-butylhydroperoxide gives rise to another form of damage profile that is also different from that produced by hydroxyl radicals in a cell-free system. However, the latter dissimilarity does not exclude hydroxyl radicals as ultimate reactive species, as a very rapid repair of the induced base modifications is observed, which might have distorted the damage profile despite immediate work up. PMID- 2272305 TI - Role of metabolic activation in the carcinogenicity of estrogens: studies in an animal liver tumor model. AB - Male Syrian golden hamsters chronically exposed to certain synthetic estrogens such as diethylstilbestrol (DES) or 17 alpha-ethinylestradiol (EE2) and fed a diet containing 7,8-benzoflavone (BF) develop a high incidence of liver tumors. No such tumors are found in animals treated with estrogen or BF alone. To clarify the role of metabolic activation of the estrogen and BF in the mechanism of hepatocarcinogenesis in this animal model, the effects of pretreatment with DES and EE2 alone and in combination with BF on the metabolism of DES, EE2, and BF in hepatic microsomes, isolated hepatocytes, and hamster bile were studied. Hamsters were pretreated for up to 32 weeks. The results clearly show that DES metabolism was not significantly modified under any pretreatment regimen. EE2 metabolism exhibited a slight increase in 2-hydroxylation after pretreatment with BF and with BF plus EE2. The most pronounced effect was observed in BF metabolism after pretreatment with BF, with BF plus DES, and with BF plus EE2: the metabolic rate was increased and several new metabolites that were not found in untreated or estrogen-pretreated animals were formed. These metabolites were tentatively identified as BF-dihydrodiol and dihydroxy-BFs. The formation of these new BF metabolites was accompanied by a change in the activities of certain cytochrome P 450 isoenzymes in hamster liver microsomes. The results of this study imply that metabolic activation of BF rather than of the estrogens plays an important role in the mechanism of carcinogenesis in this animal liver tumor model. PMID- 2272306 TI - Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneuploidy induction and neoplastic cell transformation. AB - Neoplastic cell transformation induced by estrogens and some other carcinogens such as benzene appears to involve the induction of mitotic aneuploidy rather than DNA damage and point mutations. As metabolic activation may also play an important role in the mechanism of carcinogenesis of these nongenotoxic compounds, we have studied the interaction of reactive quinone metabolites of various estrogens and of benzene with the major microtubular protein, tubulin, in a cell-free system. Covalent binding of the radioactively labeled metabolites to the alpha- and beta-subunit of tubulin was found to depend on the structure of the metabolite. When the adducted tubulins were tested in vitro for their ability to polymerize to microtubules, inhibition of microtubule assembly was observed in every case, although to varying extents. It is proposed that the formation of covalent tubulin adducts may impair the formation of mitotic spindles and thus contribute to chromosomal nondisjunction and aneuploidy induction. PMID- 2272307 TI - Quantification of thioguanine-resistant lymphocytes from mice irradiated in vivo. AB - Adult mice were Co-60 gamma irradiated, and 7 months later splenocytes were isolated, cultured in microwells, and the frequency of hprt-deficient mutants was determined by measuring the cloning efficiency in media with 6-thioguanine. The mutant frequency at 2, 4, and 6 Gy was 1.6 x 10(-5), 4.4 x 10(-5), and 12.7 x 10( 5), respectively. The frequency of spontaneous mutants was 2.5 x 10(-6). The effect of metabolic cooperation on the cloning efficiency of thioguanine resistant T-cells in selective medium was evaluated in co-cultures with wild-type T-cells. We found that the growth of hprt-deficient T-cells is supported in the presence of thioguanine-inactivated wild-type splenocytes up to a cell density of 5 x 10(5) cells per well. When cell density was higher, cell growth was inhibited. Possibilities and limitations of cloned lymphocytes for the analysis of somatic mutations that occur in vivo are discussed. PMID- 2272308 TI - Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm. AB - A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria. PMID- 2272310 TI - Modulating factors in the expression of radiation-induced oncogenic transformation. AB - Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene. PMID- 2272311 TI - Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts. AB - Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. We have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B1. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone. PMID- 2272309 TI - Retroviruses as genetic tools to isolate transcriptionally active chromosomal regions. AB - By exploiting the ability of retroviruses to move genes into random sites of mammalian genomes and by exploiting some features of their replication, retrovirus vectors have been developed that select for instances in which the virus integrates into expressed genes. Since integrated proviruses tag transcriptionally active sites, the vectors provide a means to identify and isolate promoters active in different cell types. Furthermore, the viruses may be useful as insertional mutagens, since they select for instances in which integration occurs into expressed sites. This reduces the number of integrants needed to screen for loss of gene function and may enable genes controlling phenotypes in mammalian cells to be isolated. PMID- 2272312 TI - Retinoic acid induced differentiation and commitment in HL-60 cells. AB - Human leukemic HL-60 cells are an established model for studies of differentiation induction. Retinoic acid (RA), 2 x 10(-6) M, was used to induce terminal differentiation, assayed as nitroblue tetrazol reduction (NBT) and expression of monocytic surface antigens, which were detected by monoclonal antibody Leu M3. In addition, transferrin receptor expression and the number of S + G2 + M-phase cells were determined. With a 12-hr RA incubation, only a decrease of transferrin receptor expression was found, with no change in other parameters. At least 96 hr RA incubation was necessary to induce terminal differentiation, with most cells being positive for NBT and M3. Cells induced with RA for 12 hr and subsequently recultured in liquid culture gradually expressed the differentiated phenotype and lost transferrin receptor expression. The number of S + G2 + M-phase cells in the cultures decreased drastically. After 12 hr RA exposure and 120 hr reculture without RA, the differentiation profile was comparable to that of cells that had been induced with RA for 96 hr. In reculture for up to 120 hr there was no evidence of loss of viability or regrowth of possibly residual undifferentiated cells. From these studies, we conclude that HL 60 cells become committed to terminal differentiation after half a generation time exposure to RA and remain committed for at least six generation times. PMID- 2272313 TI - Morphological, biochemical, and molecular biological characterization of a rat rhabdomyosarcoma cell line during differentiation induction in vitro. AB - BA-HAN-1C is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotubelike giant cells. Exposure to retinoic acid resulted in an inhibition of proliferation and a marked increase in cellular differentiation. The number of myotubelike giant cells significantly increased, and about 30% of the mononuclear tumor cells exhibited morphological features of rhabdomyogenic differentiation which were not observed in the mononuclear cells of untreated cultures. Morphological differentiation was paralleled by an increase in total creatine kinase activity as a biochemical marker of differentiation. These effects of retinoic acid were preceded by an increased expression of proto-oncogene raf and transient expression of proto-oncogene fos. The maximum level of fos expression was observed at 15 min and of raf at 12 hr after exposure to retinoic acid. No expression of the proto-oncogenes src, myb, myc, ros, mos, erbA, and erbB was detected. PMID- 2272314 TI - The malignant conversion step of mouse skin carcinogenesis. AB - Multiple benign squamous papillomas commonly precede the development of an occasional squamous cell carcinoma in mouse skin carcinogenesis. The incidence of carcinomas can be enhanced by treating papilloma-bearing mice with mutagens such as urethane, nitroquinoline-N-oxide, or cisplatinum. This observation suggests that a genetic change is required for malignant conversion. The malignant phenotype is characterized by a marked reduction in the transcription of specific epidermal differentiation markers, a pattern which is useful for the early diagnosis of malignant conversion. Cells expressing a benign phenotype can be obtained by introducing the v-rasHa oncogene into cultured epidermal cells by a replication-defective retrovirus. Alternatively, benign tumor cells can be cultured from papillomas induced by chemical carcinogens in vivo or from carcinogen-treated mouse epidermis. In all cases, the benign phenotype in vitro is characterized by an altered biological response to changes in extracellular calcium, an important determinant of the differentiation state of cultured normal keratinocytes. Transfection of cloned plasmid DNA into benign tumor cells has revealed that transforming constructs of the fos oncogene induce malignant conversion, whereas myc and adenovirus E1A oncogenes do not. The fos carcinomas do not express differentiation-specific epidermal markers and secrete proteases such as transin and urokinase, a set of characteristics previously noted for chemically induced skin carcinomas. Cultured normal epidermal cells, exposed to the v-ras and the v-fos oncogenes simultaneously, are malignantly transformed. Alone, the fos oncogene does not detectably alter the phenotype of normal keratinocytes. These studies indicate that a limited number of genes is involved in epidermal carcinogenesis. PMID- 2272315 TI - Growth-related alterations during liver carcinogenesis: effect of promoters. AB - Bromodeoxyuridine labeling of DNA, binuclearity counting, and flow cytometric analysis of isolated hepatocytes and hepatocyte nuclei has been used to assess hepatocellular growth patterns related to liver carcinogenesis. Three growth patterns can be distinguished. Mononucleating growth is observed during liver regeneration and after treatment with the tumor promoter 2-acetylaminofluorene (2 AAF) and its analogue 4-AAF. In this growth mode binucleation does not occur, resulting in a decrease in the fraction of binucleated cells. Binucleating growth is observed during normal liver development and after treatment with compounds such as phenobarbital, characterized by progressive polyploidization and maintenance of a binucleated cell fraction. Diploid growth is the growth pattern of neoplastic liver hepatocytes. Most of the cells in neoplastic lesions (foci, nodules, and carcinomas) are diploid, in contrast to the normal liver. Diploid tumor cells have a much higher proliferative activity than tetraploid tumor cells, suggesting that the latter may possess a limited growth potential that makes abrogation of binucleation proliferatively advantageous. PMID- 2272316 TI - Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines. AB - It has been demonstrated in several model systems that tumors arise in a multistage process. Carcinogenic aromatic amines are complete carcinogens, which usually produce tumors in typical target tissues without any additional treatment. The tissue specificity, however, cannot readily be explained by genotoxic effects, and the role of secondary effects is not well understood. Promotional pressure on initiated cells can be produced by endogenous factors but also by the chemical itself. Comparison of the effects on rat liver of 2 acetylaminofluorene (AAF) and trans-4-acetylaminostilbene (AAS) provides some evidence that initiating and promoting properties of these chemicals can be separated. AAS is a strong initiator in rat liver but seems to lack promoting activity; AAF is a less efficient initiator but has tumor promoting properties. The results obtained so far indicate that promoting pressure is not produced by the acute, cytotoxic effects of AAF. It is therefore concluded that nongenotoxic, possibly receptor-mediated effects are involved. PMID- 2272317 TI - Development of HPLC methods for the purification and analysis of plasma membrane glycoproteins. AB - High resolution HPLC techniques such as affinity chromatography (AC), ion exchange chromatography (IEC), and size exclusion chromatography (SEC) were used successfully for separations of hydrophobic plasma membrane glycoproteins. We have tested a lot of commercially available columns for IEC and SEC and performed the purification of the crude plasma membrane extract with the most suitable columns. By using immobilized ligands with different specificities and sequential affinity chromatography, it is possible to obtain a preliminary structural characterization of the interesting carbohydrate residues of membrane glycoproteins. PMID- 2272318 TI - Synthetic tumor-associated glycopeptide antigens. AB - Glycopeptides with TN antigen (GalNAc)Ser/Thr and T-antigen structures (beta Gall 3GalNAc)Ser/Thr, described as tumor-associated antigens, were synthesized and coupled to bovine serum albumin. Alternatively, synthetic methods for the construction of beta-anomeric analogues of the TN and T-antigen glycopeptides were developed, aiming at antigenic structures having a varied stereochemistry of the linkage between the carbohydrate and the peptide moiety. As a further type of potential tumor-associated antigen, fucosyl-chitobiose asparagine glycopeptides were synthesized, deprotected, and coupled to bovine serum albumin. The chemical methods developed now make the complex sensitive glycoprotein partial structures accessible in analytically pure form and in preparative amounts. PMID- 2272319 TI - Growth control in mammalian cells by cell-cell contacts. AB - Growth of normal diploid mammalian cells in vitro is strongly regulated by the actual cell density. Cell-cell contacts via specific plasma membrane glycoproteins whose glycan moieties interact with specific receptors has been found to be a main growth regulatory principle. Malignant growth is suggested to result from impaired function of these receptors. PMID- 2272321 TI - Workshop on fiber toxicology research needs. PMID- 2272320 TI - The role of the Thomsen-Friedenreich antigen as a tumor-associated molecule. AB - The Thomsen-Friedenreich antigen (Gal-GalNAc) represents a tumor-associated molecule, which is assumed to be one of the few chemically well-defined antigens with a proven association with malignancy. In order to analyze the role of the carbohydrate structure Gal-GalNAc for gastrointestinal tumors, we immunized Balb/c mice with MCF-7 breast tumor cells together with synthetic Gal-GalNAc linked to a BSA carrier. One monoclonal antibody (82-A6) was established which recognizes the Thomsen-Friedenreich antigen according to the biochemical and serological analysis presented here. In contrast to the studies performed in the past, immunohistochemical results using this antibody 82-A6 did not exhibit a reactivity clearly restricted to tumors. Preliminary biochemical analysis revealed that the T-determinant is detectable in the high-molecular weight range (about 1000 kD), suggesting that the Gal-GalNAc epitope is found on mucinlike glycoproteins. Tumor restriction of Thomsen-Friedenreich antigen may therefore be determined either by the protein backbone or by the beta-glycosidic linkage of the carbohydrate structure to the protein. PMID- 2272322 TI - Historical developments and perspectives in inorganic fiber toxicity in man. AB - The first patient known to have died from asbestosis (1900) began work in 1885, approximately 5 years after the industrial use of asbestos began in Britain. Mineral particles were found in his lungs. No special comment was made of their fibrous nature then nor when the first case was reported in 1924. The various neoplasms attributed to asbestos in the next decades posed an additional question: What influence did the fibrous shape of the particles have on carcinogenic potential? The cogency of the problem was amplified by the identification in humans of asbestos-like neoplasms with a fiber other than asbestos (erionite) and by the production of such neoplasms in experimental animals with a variety of man-made inorganic fibers, often used as substitutes for asbestos. The lessons learned about asbestos may help guide us in evaluating current fiber problems. PMID- 2272323 TI - A novel pathway to the ultimate mutagens of aromatic amino and nitro compounds. AB - Photolysis of arylazides in aqueous media was recently found to generate presumed nitrenium ions, species which are generally considered as the ultimate mutagens/carcinogens derived from arylamines and nitroarenes. The primary photolysis products of arylazides, the arylnitrenes, can possibly react as electrophiles themselves, or they can be protonated and thus form the electrophilic nitrenium ions. Numerous arylazides and aryldiazides can be photoactivated to short-lived mutagens detectable in Salmonella typhimurium TA98. Structure-activity comparisons between arylazides and the matching arylamines and nitroarenes show correlations; e.g., phenyl azide and methyl-substituted phenyl azides are not mutagenic or only weakly mutagenic like aniline, nitrobenzene, and their methyl homologues, whereas 4-azidodiphenyl, 2-azidofluorene, 1-azidopyrene, azido-IQ, and azido-isoIQ are increasingly mutagenic in that order, like the matching amino and nitro compounds. It is hypothesized on the basis of these data that the nitrene/nitrenium ion is the reactive intermediate common to the three mutagenic pathways and that the reaction of the nitrene/nitrenium ion with DNA is rate limiting for the overall mutagenic process in Salmonella. The photochemical generation from arylazides of the reactive species, the nitrene/nitrenium ions, opens new perspectives for the understanding of the genotoxic activity of arylamines and nitroarenes in general and, specifically, of the food mutagens/carcinogens of the IQ type. PMID- 2272324 TI - Human occupational and nonoccupational exposure to fibers. AB - Human exposure to fibers in occupational and nonoccupational environments has been a health concern for nearly a century. In this review, selected results from the literature are presented to highlight the availability, limitations, and interpretive difficulties associated with the past and current human fiber exposure data sets. In the traditionally defined asbestos fibers, large amounts of the data available suffer from the diversity of sample collection and analysis methods. Two simple generalizations suggest that occupational exposures are several orders of magnitude higher than that of environmental exposures; and currently extant data and the current routine measurement practices present significant difficulties in the consistent interpretation of the data with respect to health effects. The data on the human exposures to man-made vitreous fibers are much more complete than the data on asbestos exposure, while exposure data on other man-made fibrous materials are lacking. The human exposure data to many minerals which, at times, exist in fibrous habit, are very scanty, and in view of the biological activity of some of these fibers, this lack may be of significant concern. PMID- 2272325 TI - Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease. AB - Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air. PMID- 2272327 TI - The relationship between fibrosis and cancer in experimental animals exposed to asbestos and other fibers. AB - The association between occupational asbestos exposure and the development of both pulmonary fibrosis or asbestosis and pulmonary carcinomas is well documented. It has been suggested that the two pathological conditions are associated with asbestos-related carcinomas developing from areas of asbestosis and not occurring when exposure has been too low to produce this type of pulmonary scarring. Experimental inhalation studies so far published have not been designed to examine this association specifically, but many publications have reported that asbestos samples producing high levels of fibrosis is experimental animals are also very carcinogenic. Samples of asbestos or man-made fibers that produce little fibrosis also produce few tumors. These works are reviewed. In order to examine the association between fibrosis and tumor production in more detail, groups of animals with and without pulmonary tumors and with individual fibrosis measurements were assembled from a number of inhalation studies undertaken over a period of years at this Institute. It was found that animals with pulmonary tumors had almost double the amount of pulmonary fibrosis as animals of similar age that did not. In a few of the animals where tumors were found at an early stage of development, their origin from fibrotic areas could be confirmed, although in most cases where tumor deposits were widespread this was not possible. Experimental confirmation of the site of origin of most pulmonary tumors in asbestos-treated rats would require new studies with rats examined specifically at an age when early tumors would be expected. PMID- 2272326 TI - Human disease consequences of fiber exposures: a review of human lung pathology and fiber burden data. AB - Inhalation of asbestos fibers results in a variety of neoplastic and nonneoplastic diseases of the respiratory tract. Some of these diseases, such as asbestosis, generally occur after prolonged and intensive exposure to asbestos, whereas others, such as pleural mesothelioma, may occur following brief exposures. Inhalation of nonasbestiform mineral fibers can occur as well, and these fibers can be recovered from human lung tissue. Thus, there has been considerable interest in the relationship between mineral fiber content of the lung and various pathologic changes. Techniques for fiber analysis of human tissues have not been standardized, and consequently results may differ appreciably from one laboratory to another. In all reported series, extremely high fiber burdens are found in the lungs of individuals with asbestosis. Although there is a correlation between the tissue concentration of asbestos fibers and the severity of pulmonary fibrosis, further studies of the mineralogic correlates of fiber-induced pulmonary fibrosis are needed. Mesothelioma may occur with fiber burdens considerably less than those necessary to produce asbestosis. More information is needed regarding the migration of fibers to the pleura and the numbers, types, and dimensions of fibers that accumulate at that site. Patients with asbestosis have a markedly increased risk for lung cancer, but the risk of lung cancer attributable to asbestos in exposed workers without asbestosis who also smoke is controversial. Combined epidemiologic-mineralogic studies of a well-defined cohort are needed to resolve this issue. In addition, more information is needed regarding the potential role of nonasbestos mineral fibers in the pathogenesis of lung cancer. PMID- 2272328 TI - Effects of fiber characteristics on lung deposition, retention, and disease. AB - There is abundant epidemiologic evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans, as well as limited evidence for such effects in workers exposed to slag and rockwool fibers. Epidemiological evidence for human disease from inhalation exposures to conventional fibrous glass is negative. While health concerns based on the morphological and toxicological similarities between man-made fibers and asbestos are warranted, it is important to note that most of the toxicological evidence for glass fiber toxicity in laboratory animals is based on nonphysiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. Man-made fibers have produced lung fibrosis and mesotheliomas in such tests, albeit at much lower yields than asbestos. For all durable mineral fibers, critical length limits must be exceeded to warrant concern about chronic toxicity; i.e., 2 microns for asbestosis, 5 microns for mesothelioma, and 10 microns for lung cancer. Fiber width must be less than 0.1 microns for mesothelioma, and larger than this limit for asbestosis and lung cancer. The human health risks for most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aero-dynamic diameters approximately 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers that do penetrate into the lungs are not persistent within the lungs for most fibrous glass products due to mechanical breakage into shorter lengths and overall dissolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272329 TI - In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays. AB - In vitro studies employing organ cultures, primary cell cultures, cell lines, and bacterial systems have been used to assess the toxicity, mutagenicity, and carcinogenic potential of asbestos and nonasbestos fibers. These experiments have been useful in defining mechanisms contributing to the causation of fiber associated lung diseases. Long (greater than 8 microns), thin asbestos fibers are more active in vitro than short (less than or equal to 2 microns) fibers or nonfibrous particles, an observation supporting the importance of fiber dimension in disease. Although in vitro bioassays cannot evaluate characteristics such as clearance and/or durability of fibers which may be critical determinants of fiber toxicity in lung, they can be used both to address dosimetry at the cellular level (i.e., number of fibers per cell that elicit a measurable biologic end point) and to evaluate preventive approaches to fiber-induced cell injury. Development of in vitro models employing target cells of the lung, i.e., mesothelial cells, tracheobronchial epithelial cells, and lung fibroblasts, as well as carefully characterized preparations of fibers and particles, will be necessary to evaluate whether in vitro bioassays are amenable to predicting the pathogenic potential of synthetic and naturally occurring fibers comparatively. PMID- 2272330 TI - Parental occupation and childhood cancer: review of epidemiologic studies. AB - Parental occupational exposures might affect childhood cancer in the offspring through genetic changes in the ovum or sperm or through transplacental carcinogenesis. The 24 published epidemiologic studies of this association have all used case-control designs, with controls generally selected from birth certificates or from general population sampling. Occupational exposures were inferred from job titles on birth certificates or through interviews. A large number of occupation-cancer associations have been reported, many of which were not addressed or not confirmed in other studies. Several associations have been found with consistency: paternal exposures in hydrocarbon-associated occupations, the petroleum and chemical industries, and especially paint exposures have been associated with brain cancer; paint exposures have also been linked to leukemias. Maternal exposures have received much less attention, but studies have yielded strongly suggestive results linking a variety of occupational exposures to leukemia and brain cancer. The primary limitations in this literature are the inaccuracy inherent in assigning exposure based on job title alone and imprecision due to limited study size. Although no etiologic associations have been firmly established by these studies, the public health concerns and suggestive data warrant continued research. PMID- 2272331 TI - Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens. AB - Dibenz(a,h)anthracene (DBA), a carcinogenic, polycyclic aromatic hydrocarbon ubiquitous in the environment, is metabolized by the hepatic microsomal fraction of immature Sprague-Dawley rats pretreated with Aroclor 1254 to 27 ethyl acetate extractable metabolites. More than half of these metabolites (51%) consisted of trans-1,2-; -3,4-; and -5,6-dihydrodiols including their identified secondary metabolites. The three trans-dihydrodiols (4.9, 15.8, and 0.6% of total metabolic conversion) were highly enriched in their R,R enantiomers (85, 71, and 98%) as determined by high performance liquid chromatography on suitable chiral stationary phases. This is explained on the basis of the stereoselective epoxidation of DBA by cytochrome P-450c (induced by Aroclor 1254) followed by regioselective hydration catalyzed by microsomal epoxide hydrolase. Determination of the bacterial mutagenicity by measuring the reversion rate of histidine dependent Salmonella typhimurium TA100 to histidine prototrophy revealed marked differences in the mutagenicity of the enantiomers of the trans-dihydrodiols of DBA when activated by the same metabolizing system as used in the metabolism studies. In the case of trans-1,2- and -5,6-dihydrodiol, the S,S enantiomers were converted to more mutagenic metabolites than their corresponding optical antipodes, whereas in the case of trans-3,4-dihydrodiol it was the R,R enantiomer that produced the stronger mutagens. Therefore, both regio- and stereoselectivity of the metabolizing enzymes attribute to the dominant role of trans-3,4 dihydrodiol in the mutagenicity of DBA. PMID- 2272332 TI - Sulfotransferase-mediated chlorination of 1-hydroxymethylpyrene to a mutagen capable of penetrating indicator cells. AB - Methylated polycyclic aromatic hydrocarbons are common in the human environment. Many of them are stronger carcinogens than their purely aromatic congeners. They may be metabolized to benzylic alcohols. We report here on biochemical and toxicological characteristics of 1-hydroxymethylpyrene (HMP), a typical representative of this class of compounds. Rat liver cytosol, fortified with 3' phosphoadenosine-5'-phosphosulfate, converted HMP into its sulfate ester (HMPS), HMPS bound covalently to isolated DNA. In physiological buffer at 37 degrees C, HMPS had a half-life of 2 min, the major decomposition product being HMP. Thus, cyclic activation is possible. When Cl- anions were present at physiological concentrations, an additional reaction product of HMPS, 1-chloromethylpyrene (ClMP), could be identified on the basis of its chromatographic properties and its mass spectrum, using the authentic standard for comparison. ClMP was shorter lived in buffer than HMPS. ClMP reacted with DNA, the adduct pattern in the 32P postlabeling analysis being similar, or identical, to that of HMPS. ClMP proved to be a very potent mutagen in Salmonella typhimurium, whereas HMPS, and HMP in the presence of a sulfate-conjugating system, showed strong mutagenicity only when Cl- or Br- ions were present in the exposure buffer. It is concluded that HMPS is capable of reacting with DNA, but is hampered in its distribution by membrane barriers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272333 TI - Rat and human liver cytosolic epoxide hydrolases: evidence for multiple forms at level of protein and mRNA. AB - Two forms of human liver cytosolic epoxide hydrolase (cEH) with diagnostic substrate specificity for trans-stilbene oxide (cEHTSO) and cis-stilbene oxide (cEHCSO) have been identified, and cEHCSO was purified to apparent homogeneity. The enzyme had a monomer molecular weight of 49 kDa and an isoelectric point of 9.2. Pure cEHCSO hydrolyzed CSO at a rate of 145 nmole/min/mg. TSO was not metabolized at a detectable level, and like cEHTSO, the enzyme was about three times more active at pH 7.4 than at pH 9.0. Unlike cEHTSO, cEHCSO was efficiently inhibited by 1 mM 1-trichloropropene oxide (90.5%) and 1 mM STO (92%). Similarly, liver cEH purified 541-fold from fenofibrate induced Fischer 344 rats was shown to be a native 120 kDa dimer of two 61 kDa subunits. The enzyme expressed maximum activity of 205 nmole/min/mg at pH 7.4 toward the diagnostic substrate TSO with an apparent Km of 1.7 microM. In Western blots, polyclonal antibodies against rat liver cEH were shown to recognize a single 61 kDa protein band from liver cytosol of rat, mouse, guinea pig, Syrian hamster, and rabbit. This antibody precipitated neither human liver cEHTSO or cEHCSO. Antibodies against rat liver microsomal epoxide hydrolase reacted with cEHCSO in the Western blot and on immunoprecipitation. Using antibodies against rat liver cEH, 24 positive clones were picked upon colony blot screening of a pEX 1/E. coli POP 2136 expression library.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272334 TI - Mass spectrometric peptide mapping analysis and structural characterization of dihydrodiol dehydrogenase isoenzymes. AB - The direct molecular weight determination and structural analysis of polypeptides and peptide mixtures have become amenable by the recent development of fast atom bombardment (FABMS) and 252Cf-plasma desorption (PDMS) mass spectrometry. FABMS and PDMS peptide mapping, i.e., the direct analysis of peptide mixtures resulting from proteolytic digestion, have been developed as powerful methods for the structural characterization of epoxide-metabolizing isoenzymes. The major advantage of this approach is provided by the selectivity of the endoproteolytic cleavage, combined with the specific and accurate molecular weight determination of complex digest mixtures containing peptides up to several thousands daltons in size. Furthermore, the mass spectrometric peptide mapping analysis can be combined with a range of protein-chemical modification reactions and with sequential degradation such as by carboxypeptidases. Both FABMS and PDMS peptide mapping have already been successfully applied to the structural differentiation of glutathione transferase and epoxide hydrolase isoenzymes in cases where references sequence data for at least one isoenzyme form was available. In the application described here, for a series of dihydrodiol dehydrogenase (DDH) isoenzymes with hitherto undetermined primary structures, a direct correlation between the structural differentiation from peptide mapping data and differences in their substrate specificities could be demonstrated. The mass spectrometric peptide mapping analysis of isoenzymes proved to be an efficient basis for the elucidation of the structure of one major DDH isoenzyme form; partial sequence data for this protein are reported. PMID- 2272335 TI - Genetically engineered V79 Chinese hamster cells metabolically activate the cytostatic drugs cyclophosphamide and ifosfamide. AB - V79 cells, genetically engineered to express active cytochromes P450IIB1 and P450IA1, were used to study the cytotoxicity and mutagenicity of cyclophosphamide and ifosfamide. Cyclophosphamide, tested up to a concentration of 2 mM, was not cytotoxic in V79 nor in the P450IA1-expressing V79-derived cell line XEM2. Pronounced cytotoxicity was, however, observed in the P450IIB1-expressing V79 derived cell line SD1. Induction of gene mutations (acquisition of 6-thioguanine resistance) was observed in SD1 cells as well, but the effects were weak. Ifosfamide was inactive in V79 cells, but was cytotoxic in SD1 cells. Ifosfamide mustard, an active metabolite of ifosfamide, was equally cytotoxic and showed similar mutagenic effects in SD1 and parental V79 cells. The results indicate that cyclophosphamide and ifosfamide are metabolically activated by cytochrome P450IIB1. In contrast, cytochrome P450IA1 was not capable of activating cyclophosphamide. Thus, V79-derived cell lines defined for their expression of a specific form of cytochrome P-450 can be used as diagnostic tools to identify the cytochrome P-450 that is responsible for the metabolic activation of drugs. PMID- 2272336 TI - Studies of the expression of the cytochrome P450IA, P450IIB, and P450IIC gene family in extrahepatic and hepatic tissues. AB - We have studied the expression of three P-450 gene subfamilies in hepatic and extrahepatic tissues using the sensitive RNAse A protection assay. Members of the P450IA subfamily, which encodes the major methylcholanthrene-inducible cytochromes P-450, were found to be not expressed in extrahepatic tissues of untreated animals, raising the question whether these P-450 play a role in the metabolism of carcinogens in unexposed individuals. In contrast, members of the P450IIB family, some of which encode the major phenobarbital-inducible cytochromes P-450, were found to be expressed in some extrahepatic tissues of untreated rats and here most notably in the lung and in sebaceous glands. Members of the P450IIC family, which encode some constitutively expressed cytochromes P 450, were found to be expressed exclusively in the liver. PMID- 2272337 TI - Genetic modulation of the cellular antioxidant defense capacity. AB - Oxidants are ubiquitous in our aerobic environment. While they are always toxic, they can also exert pathophysiological effects at low concentrations and play an etiological role in human disease. For example, oxidants can stimulate cell growth and act as tumor promoters. The cellular antioxidant defense system attenuates the effect of oxidants and consists of low molecular weight components and several enzymes. Most important are catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidase. We are attempting to elucidate the role of CAT and Cu,Zn-SOD in oxidant tumor promotion of mouse epidermal cells JB6. We have found that the promotable clone 41 possesses 2- to 3-fold higher levels of activity, protein, and stationary mRNA of CAT and Cu,Zn-SOD than does the nonpromotable clone 30. We propose that the growth-stimulatory effect of oxidants is more pronounced in promotable clone 41 because it is better protected from oxidant toxicity. In order to corroborate this model, we have constructed JB6 cells with higher levels of Cu,Zn-SOD and CAT by transfection with expression vectors containing cDNA for these genes. On the other hand, cells with decreased amounts of Cu,Zn-SOD have been obtained by their stable transfection with a vector containing SOD-cDNA in the antisense orientation. These cell clones with modified antioxidant enzyme complements are being characterized. In particular, their promotability by oxidants and their sensitivity to killing and oxidative macromolecular damage are being measured. Certain tumor promoters that lack oxidizing properties may generate a cellular prooxidant state by a variety of mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272338 TI - Activity of carcinogens that bind to the C8 position of guanine residues in an assay specific for the detection of -2 frameshift mutations in a defined hot spot. AB - In this paper we describe a reversion assay specific for the detection of -2 frameshift mutations occurring within short stretches of alternating GC sequences. We have compared a series of chemical carcinogens that all bind covalently to the C8 position of guanine residues for their potency in inducing revertants in this assay. Large variations in potency are found within the list of compounds that were tested. The most potent chemicals tested induce the reversion frequency by a factor of 10(5) over background, whereas others only increase it by two orders of magnitude. These differences are discussed in terms of the conformational changes that the different C8-guanine adducts induce in DNA. PMID- 2272339 TI - Molecular mechanisms of DNA damage initiated by alpha, beta-unsaturated carbonyl compounds as criteria for genotoxicity and mutagenicity. AB - alpha, beta-Unsaturated carbonyl compounds are important not only from a theoretical but also a practical standpoint. These ubiquitous compounds can interact with DNA through various mechanisms. The predominant interaction is the formation of cyclic 1,N2-deoxyguanosine adducts; 7,8-cyclic guanine adducts are also found. We have synthesized and characterized the stereoisomers of adducts formed by about 20 alpha, beta-unsaturated carbonyl compounds. The different types of adducts and the mutagenic and genotoxic response can be explained by the molecular structures of the agents. Compounds forming saturated cyclic adducts are mutagenic in S. typhimurium strain TA100 and to a lesser extent in TA1535. Substances with a leaving group at the C-3 position form unsaturated conjugated cyclic adducts and are mutagenic only in the His D3052 frameshift strains with an intact excision repair system (no urvA mutation). Metabolic epoxidation of the double bond and other metabolic activation, e.g., activation of the nitrogroups via nitroreductases, were also found to contribute to genotoxic and mutagenic activities. Our results have further elucidated the genotoxic mechanisms of these compounds; however, additional investigations are required for a complete understanding of the genotoxic activity of this class of compounds. PMID- 2272340 TI - Adenosine involvement in postictal events in amygdala-kindled rats. AB - The actions of adenosine in modulating amygdala kindling were examined using the stable adenosine analog 5'-N'-ethylcarboxamidoadenosine (NECA) and caffeine, an adenosine antagonist. Systemically administered NECA was found to significantly reduce the rate of postictal spiking and to significantly increase the duration of postictal EEG depression in amygdala kindled rats. In contrast, systemically administered caffeine significantly increased kindled seizure duration and reduced the duration of postictal EEG depression. Systemic administration of the methylxanthine derivative, 8-sulfophenyl theophylline (8-PST), failed to block the effects of NECA on kindling. Since systemically administered 8-PST blocks peripheral adenosine receptors, but has only limited CNS activity, the effects of NECA appear to be centrally mediated. These observations further demonstrate a role for adenosine in postictal phenomena and support the hypothesis that a release of endogenous adenosine contributes to the termination of ongoing seizure activity. PMID- 2272341 TI - Use of maximal dentate activation to study the effect of drugs on kindling and kindled responses. AB - Maximal dentate activation is a paroxysmal event characterized by the appearance of bursts of large amplitude population spikes in the dentate gyrus that has been shown to be associated with the production of afterdischarges in limbic circuits. Repeated elicitation of maximal dentate activation in the anesthetized rat produces a progressive increase in afterdischarge duration. The present work examined the role of NMDA receptor activation in this process. The effects of MK 801 (a systemically active NMDA receptor complex antagonist) and imipramine and desipramine (tricyclic antidepressants recently reported to have NMDA receptor coupled channel blocking properties) were studied. MK-801, at 0.5 mg/kg, prevented the lengthening of the duration of maximal dentate activation. At 2 mg/kg, MK-801 also shortened the duration of maximal dentate activation already established. Imipramine showed a similar dose-dependent response pattern with 15 mg/kg and 50 mg/kg respectively. Desipramine (50 mg/kg) was similar to imipramine (50 mg/kg) in its effect. Thus, the drugs studied were effective at shortening limbic epileptiform discharges. These results support the use of this model to examine drug effects and strengthen the hypothesis that NMDA receptors play a critical role in seizure generation in the limbic system and, specifically, in the lengthening of the duration of maximal dentate activation. PMID- 2272342 TI - Effects of pentetrazol on neuronal activity and on extracellular calcium concentration in rat hippocampal slices. AB - Effects of pentetrazol (PTZ) were studied on neuronal responses in dentate granule cells and area CA1 hippocampal pyramidal cells with intra- and extracellular recording techniques. PTZ induced spontaneous epileptiform field potential transients in areas CA3 and CA1, but not in the dentate gyrus. The concentration optimum for induction of spontaneous epileptiform activity was 2 mM. The epileptiform activity compared in many respects to that induced by GABA antagonists such as picrotoxin, bicuculline and penicillin. Paired pulse stimulus induced responses were affected by concentrations of 0.5 mM. In the concentration range 0.5-2 mM mostly disinhibitory effects were noted. Stimulus induced Ca2+ concentration changes were found to be maximally augmented at concentrations of 2 5 mM. In this range, intracellular studies revealed a block of frequency habituation and an increase in input resistance. The convulsant action of PTZ decreased at concentrations above 5 mM, probably due to a decrease of inward currents. We suggest that the action of PTZ in screening studies for anticonvulsants is mostly due to a decrease of GABAA-receptor mediated IPSPs. PMID- 2272343 TI - Effect of intraventricular administration of calcium on the lowering of brain dopamine level in epileptic mice. AB - Dopamine (DA) levels in the various brain regions of epileptic mice (El mice) were compared immunohistochemically with those in ddY mice (the mother strain of El mice) using a fluorescence microphotometry system. The fluorescence intensities of DA in the neostriatum and nucleus accumbens septi in El mice were approximately 11-15% (P less than 0.01) and 13% (P less than 0.01) lower than in ddY mice. On the other hand, the lower DA amounts in these regions of El mice were improved by intraventricular administration of CaCl2 (10 mumol/kg). The brain regions in which the amount of DA was increased by calcium were areas where high levels of calmodulin and tyrosine hydroxylase are distributed. This finding reconfirmed our previous report that the biogenic amine level disorder in El mice was related to a calcium ion level disorder through a central calcium-calmodulin dependent biogenic amine-synthesizing mechanism, and this might increase their susceptibility to epileptic convulsions. PMID- 2272344 TI - Failure of acute diphenylhydantoin to affect the spontaneous electrical activity of dopamine cells. AB - Diphenylhydantoin (DPH) has recently been reported to produce dopaminergic (DA) supersensitivity in animals. These results have suggested that the dyskinesias observed in humans after DPH, although rare, might be regarded as a neuroleptic like effect. Indeed dyskinesias would be induced by an inactivation of post synaptic DAergic receptors, operated by DPH, and therefore reminiscent of that observable in neuroleptic treatment. In order to investigate this matter, we studied the effects of i.v. DPH on the extracellular single unit activity of DAergic cells located in mid-brain areas of rats. DPH was injected alone or in combination with DA antagonists such as L-sulpiride (L-SULP) and haloperidol (HAL), or the DAergic agonist apomorphine (APO). Our results show that DPH did not affect spontaneous DAergic firing rate and also failed to modify the known action of the DA agonists and antagonists which were tested on these neurons. PMID- 2272345 TI - A randomised double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy. AB - The efficacy of lamotrigine (LTG), a new antiepileptic drug (AED) chemically unrelated to drugs in current use, was evaluated in 21 in-patients (18 males, 3 females; mean age 34.6; range 23-42 years) with severe refractory epilepsy. An add-on double-blind placebo-controlled crossover design was used, with 12 week treatment periods, and a 6 week washout period. Subjects were allocated to 1 of 2 dosing schedules according to their concomitant AEDs. Doses were increased according to clinical response. Although there was no significant reduction in total seizure count during the lamotrigine treatment period compared to placebo, there appears to be a drug effect as there was a marked reduction in generalized tonic-clonic seizures in favour of lamotrigine in the last 4 weeks of the treatment period. There was no significant difference in volunteered adverse experiences during active and placebo treatment. Concomitant serum AED concentrations, biochemical and haematological parameters were unaffected by lamotrigine treatment. PMID- 2272346 TI - Single-dose efficacy evaluation of loreclezole in patients with photosensitive epilepsy. AB - Photosensitivity can be used as a model in short-term studies for assessing the efficacy of new antiepileptic drugs in man. As a quantitative measure of photosensitivity, the photosensitivity range is employed. This is the range between the highest and the lowest flash rate producing a photoparoxysmal response (generalized paroxysmal activity on the EEG). An efficacious new antiepileptic drug should, like all currently available antiepileptic drugs, reduce the photosensitivity range. Single-dose administration of 100-150 mg of loreclezole resulted in a decreased photosensitivity in all patients tested. This effect was attributable to loreclezole as no acute interactions with valproic acid could be demonstrated. The rapid onset of activity indicates that loreclezole readily passes the blood-brain barrier. The doses applied were very well tolerated. PMID- 2272347 TI - Neurohypophyseal hormones and excessive grooming behaviour. AB - The pattern of excessive grooming displayed by rats treated with vasopressin and oxytocin was investigated by calculating the frequencies and contribution of the behavioural elements head washing, body grooming, anogenital grooming, paw licking and scratching. In addition, the suppressive effect on peptide-induced grooming of the dopamine D1 receptor antagonist SCH 23390, of neurotensin and of the opiate receptor antagonists naloxone and naloxone-methobromide was studied. The pattern of excessive grooming induced by vasopressin and by oxytocin was characterized by the contribution of most behavioural elements to the total grooming scores. Oxytocin-induced excessive grooming was characterized by a marked increase in the frequency of anogenital grooming. SCH 23390, neurotensin and naloxone, but not naloxone-methobromide, suppressed excessive grooming induced by vasopressin and oxytocin. It is suggested that dopamine D1 receptors as well as opiate receptors located within the blood-brain barrier are involved in the excessive grooming induced by neurhypophyseal hormones. PMID- 2272348 TI - Changes in hypothalamic neuropeptide Y concentrations induced by cholecystokinin analogues. AB - Neuropeptide Y (NPY) and cholecystokinin (CCK) are two peptides involved in opposite ways in the control of food intake. A possible interaction between NPY and CCK has not yet been well defined. Two CCK derivatives with agonistic and antagonistic properties were studied with regard to their effects on brain and plasma NPY levels. The CCK agonist decreased NPY levels in plasma and in the hypothalamus but not in the other brain areas assayed. The CCK antagonist reversed the agonist-induced decrease in both plasma and hypothalamus. These results suggest a negative relation between NPY and CCK peptides, which is not surprising given their opposite role in feeding regulation. The hypothalamus, a preferential site of this regulation, appears to be the brain area most involved in the NPY-CCK interaction. The plasma NPY level variations closely reflect the hypothalamic profile, suggesting a direct release of NPY by a mechanism that remains to be investigated. PMID- 2272349 TI - Non-peptide angiotensin II receptor antagonists discriminate subtypes of 125I angiotensin II binding sites in the rat brain. AB - We have utilized quantitative autoradiography to define subtypes of 125I angiotensin II (AII) binding in rat brain. AII-1 binding (displaced by DuP 753) was found in the nucleus of the solitary tract and the hypothalamus, while AII-2 binding (displaced by WL 19) was found in the thalamus and lateral septum. These results indicate that subtypes of the AII receptor are present in the brain and the AII-1 receptor subtype is present in regions consistant with the known actions of angiotensin. PMID- 2272350 TI - Indomethacin and ibuprofen inhibit the uptake of 45Ca2+ by washed human platelets through a thromboxane A2-independent mechanism. AB - Indomethacin and ibuprofen inhibited adrenaline- and calcium ionophore A23187 stimulated 45Ca2+ uptake by isolated human platelets in a concentration-dependent manner. Mediation of these effects by thromboxane A2 (TXA2) inhibition was discounted since under the same experimental conditions, adrenaline did not stimulate TXA2 synthesis and A23187-stimulated TXA2 synthesis was only marginally inhibited by concentrations of ibuprofen and indomethacin that inhibited 45Ca2+ uptake by 50%. These data indicate that the inhibitory action of non-steroidal anti-inflammatory drugs (NSAIDs) on platelet activity may be due, at least in part, to effects on calcium mobilisation at the plasma membrane level. The present results may also be of relevance to the anti-inflammatory action of NSAIDs. PMID- 2272351 TI - Activation of propylbenzilylcholine mustard-sensitive muscarinic cholinoceptors more effectively utilizes cytosolic Ca2+ for contraction in guinea-pig intestinal smooth muscle. AB - A 50-min treatment of longitudinal smooth muscle of guinea-pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M) irreversibly inhibited the responses elicited by carbachol. However, a 90-min treatment with PrBCM had no further significant inhibitory effect on the responses to carbachol, suggesting that there are two subtypes of muscarinic cholinoceptors, PrBCM-sensitive and PrBCM-insensitive receptors. Carbachol caused a rapid increase in cytosolic Ca2+ concentrations ([Ca2+]i), which was followed by a rapid increase in muscle tension in both untreated and PrBCM-treated preparations. There was a positive correlation between [Ca2+]i (R340/380) and tension developed in response to carbachol. A regression line for the two responses was obtained in each preparation. The slope of the line obtained with untreated preparations was steeper than that obtained with PrBCM-treated preparations. These data suggest that, upon activation, PrBCM-sensitive receptors use cytosolic Ca2+ more effectively than PrBCM-insensitive receptors. PMID- 2272352 TI - Prostaglandins and gastric mucosal protection by esaprazole in rats. AB - Esaprazole, N-cyclohexyl-1-piperazineacetamide monohydrochloride, was studied for its activity to prevent gastric mucosal damage induced by several necrotizing agents in the rat. Its effects on acid gastric secretion and the role of gastric mucosal prostaglandin generation were also investigated. Esaprazole, given orally, dose dependently prevented the formation of mucosal damage induced by absolute ethanol, 0.2 N NaOH or 0.6 N HCl. This activity occurred at doses lower than the antisecretory doses. Esaprazole was also found to increase the gastric mucosal prostaglandin content but at doses that exceeded the cytoprotective doses. The failure of indomethacin to impair the gastric mucosal protection provided by esaprazole suggests that mechanisms other than mobilization of endogenous prostaglandins may be involved. PMID- 2272353 TI - Effects of apamin and nicotinic acetylcholine receptor antagonists on inferior collicular seizures. AB - These studies compared the actions of apamin and nicotinic acetylcholine antagonists on seizure genesis within the inferior collicular cortex. In vitro alpha-bungarotoxin, d-tubocurarine and gallamine all competitively displaced [125I]apamin binding to brain sections through the inferior colliculus, while intracollicular microinjection of intermediate doses of apamin (21 pmol), alpha bungarotoxin (0.3 nmol), d-tubocurarine (0.22 nmol) or gallamine (1.7 nmol) all significantly reduced the seizure initiation threshold current. However, higher doses of apamin did not cause spontaneous seizure activity, while higher doses of the nicotinic acetylcholine antagonists caused spontaneous seizures. Carbamylcholine also produced spontaneous seizures, but did not alter the seizure threshold current. N-Methyl-atropine caused a dose-related elevation of the seizure threshold current, yet microinjection of N-methyl-atropine (10 nmol) into the inferior collicular cortex reversed the effects of alpha-bungarotoxin on seizure threshold, partially opposed the effects of gallamine and d-tubocurarine, and had no effect on the ability of apamin to reduce the seizure threshold current. Thus, both the apamin-sensitive potassium channel and a variety of distinct cholinergic mechanisms contribute in vivo to seizure genesis within the inferior collicular cortex, but not through the same mechanisms. PMID- 2272354 TI - Effects of azelastine on contraction of guinea pig tracheal smooth muscle. AB - Azelastine [4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1(2H) phthalazinone hydrochloride] is a new anti-asthmatic drug. We examined the mechanism of its inhibitory action on guinea pig tracheal smooth muscle contraction by measuring membrane potential and isometric force using intracellular microelectrodes and a micro-force transducer. The mean resting membrane potential of guinea pig tracheal muscle cells was -54 mV. Perfusion with 20 mM tetraethylammonium (TEA) caused membrane depolarization and elicited spontaneous action potentials. Azelastine (1-100 microM) suppressed both the amplitude and maximal rate of rise of the action potentials in a concentration dependent manner. Complete abolition occurred at 100 microM. Similarly, azelastine (0.1-100 microM) inhibited and abolished 50 mM KCl-induced contractions. These results suggest that azelastine may inhibit voltage-dependent Ca2+ channels. Next, pretreatment of tracheal muscle (for 15 min) with azelastine (0.01-100 microM) inhibited subsequent acetylcholine (ACh) (0.01-100 microM) induced contractions. Azelastine, 100 microM, completely abolished the ACh induced contractions. In contrast, high concentrations of Ca2+ channel antagonists diltiazem (10-100 microM) or nifedipine (20 microM), and Ca2(+)-free solution, only partially depressed the ACh contractions suggesting that azelastine has an additional effect on intracellular Ca2+ release. In Ca2(+)-free solution (containing 0.5 mM EGTA), azelastine (1-100 microM) depressed and abolished the transient contractions induced by 10 microM ACh. We conclude that azelastine inhibits airway constriction by inhibiting both voltage-sensitive Ca2+ slow channels on the cell membrane and Ca2+ release from a intracellular storage site. PMID- 2272355 TI - Autoradiography of [3H]quipazine in rodent brain. AB - The distribution of binding sites for [3H]quipazine was examined in sections from rat brain. This radioligand has been demonstrated to label 5-HT3 receptors in membrane homogenate studies. Specificity of [3H]quipazine for these receptors was obtained by using 10(-7) M ICS 205-930, a highly selective 5-HT3 antagonist, to define non-specific binding. Several areas of dense 5-HT3-specific binding were detected in the medulla, most notably the nucleus of the solitary tract and the caudal portion of the spinal trigeminal tract. Low to moderate levels of 5-HT3 binding were seen in several forebrain regions, including the pyriform cortex, posterior nuclei of the amygdala, ventral tegmental area, anterior olfactory nucleus and superior colliculus. [3H]Quipazine autoradiography was also performed on brain sections from mouse, gerbil, hamster and guinea pig. Specific binding was quite low throughout most of the brains from these species; however, in all but the guinea pig, dense streaks of binding were detected in nucleus of the solitary tract (and in the mouse, the nucleus of the spinal tract of the trigeminal nerve). The distribution of 5-HT3 receptors in the brain may help explain some of the proposed CNS activities of 5-HT3-selective drugs. The anti emetic and antinociceptive activities of 5-HT3 antagonists may be mediated by receptors in the sensory areas in the brainstem. PMID- 2272356 TI - Effect of ring fluorination of epinephrine on its cardiovascular adrenoceptor activities. AB - Effects of fluorine (F) substitution on the 2- and 6-positions of the catechol ring of epinephrine (Epi) on its alpha- and beta-adrenoceptor agonist activities were studied in anesthetized dogs. Increments in heart rate and contractile force were used as measures of beta 1-adrenoceptor activity, while increases and decreases in blood pressure and decreases and increases in femoral blood flow were used as measures of alpha- and beta 2-adrenoceptor activities, respectively. F substitution on the 2- and 6-positions of the catechol ring yielded compounds with opposite receptor selectivities: 2-FEpi was a selective beta-adrenoceptor agonist with little agonist activity at alpha-adrenoceptors, while the 6-F analog was a selective a-adrenoceptor agonist with no significant beta-adrenoceptor effects. Of added significance, 2-FEpi was more potent than Epi as a beta 1 adrenoceptor agonist, while 6-F Epi was more potent than the parent compound as an alpha-adrenoceptor agonist. The possible mechanisms for the effects of ring fluorination on the adrenoceptor activities of Epi and other sympathomimetic amines are discussed. PMID- 2272357 TI - Cardiac responses to VIP and VIP-ergic-cholinergic interaction in isolated dog heart preparations. AB - Whereas i.v. administration of vasoactive intestinal peptide (VIP) to support dogs increased heart rate and decreased systemic blood pressure, sinus rate and contractile force increased in isolated right atria perfused with blood from the support dogs. VIP injected intraarterially into isolated atria induced dose dependent positive chronotropic and inotropic effects. Intracardiac parasympathetic nerve stimulation attenuated the positive cardiac responses to VIP, but neither propranolol, imipramine, nor tetrodotoxin influenced the responses to VIP. VIP given to isolated left ventricles also increased the contractile force in a dose-dependent manner. However, VIP induced a greater maximum atrial contractility than ventricular contractility. This may indicate that VIP receptor density in the ventricle was lower than in the atrium, as it has recognized that VIP-ergic nerves innervate the right atrium more densely than the left ventricle. We therefore suggest that the positive cardiac responses to VIP, together with the VIP-ergic innervation in dog hearts and vagal activation, attenuate the VIP-mediated responses at site(s) in the cyclic AMP cascade. PMID- 2272358 TI - Evidence for muscarinic receptors in endothelial cells from combined functional and binding studies. AB - The aim of this study was to characterize muscarinic receptors of the bovine coronary artery by means of a combination of mechanical relaxation and contraction responses and radioligand binding data. Fresh helical strips of bovine coronary artery with intact endothelium relaxed in response to low concentrations (0.03-1 microM) of acetylcholine (ACh) and contracted at higher concentrations while endothelium-denuded strips only contracted. The ED50 for relaxation was 0.13 microM and that for contraction 1.8 microM (without endothelium); in the presence of endothelium, contraction dose-response curves were shifted to the right and the maximum contraction was reduced. In order to determine the location of the receptors mediating vasorelaxation, apparent affinity constants (KA) of ACh for relaxant and contractile effects were determined by irreversible blockade of a fraction of receptors with propyl benzilylcholine mustard (PBCM). The affinity constants (KA) were 0.22 microM for relaxation and 13 microM (with endothelium) and 20 microM (without endothelium) for contraction. In competition binding experiments against the muscarinic antagonist, [3H]N-methylscopolamine ([3H]NMS), the apparent affinity (KI) of ACh for binding sites in homogenates of endothelium-free coronary artery was 16 microM which was not different from the affinity constant determined in functional contraction experiments. Thus, the affinity constant of ACh determined for relaxation responses with endothelium-preserved vessels had no correlate in the binding affinity as determined with endothelium-free arteries. These findings indicate that bovine coronary arteries are relaxed by ACh through muscarinic receptors located on the endothelium whereas contractions are mediated by receptors on smooth muscle cells. PMID- 2272359 TI - Angiotensin stimulates Ca2(+)-dependent action potentials in cultured smooth muscle cells. AB - The steady-state angiotensin II response was measured in primary cultures of reaggregated vascular smooth muscle cells derived from rat aorta by use of intracellular microelectrode recording of membrane potentials. Angiotensin II (10(-9)-10(-6) M) produced a depolarization which triggered a single action potential, consisting of a spike plus plateau. In addition, angiotensin II prolonged the action potential plateau and lowered input resistance. The angiotensin II-induced action potentials and the action potential plateau prolongation were inhibited by verapamil. Saralasin blocked the occurrence of angiotensin II-induced action potentials and reversed the increase in action potential duration provoked by angiotensin II. Saralasin, in the absence of angiotensin II, exhibited agonistic activity which was manifest by plateau prolongation. Therefore, angiotensin II, through interaction of the peptide with its receptor, depolarizes cultured vascular smooth muscle cells and prolongs the calcium-dependent action potentials. These effects could be mediated by the known ability of angiotensin II to stimulate production of inositol trisphosphate and diacylglycerol, and activation of protein kinase C. PMID- 2272360 TI - In vivo characterisation of novel efficacious muscarinic receptor agonists. AB - Although a number of muscarinic agonists have been used in clinical trials for Alzheimer's Disease, many of these compounds are low in potency and have only limited intrinsic efficacy. The present study describes four non-quaternary oxadiazole based muscarinic agonists from a quinuclidine and a 1-azanorbornane series. These displayed up to 1000 fold higher affinity than arecoline and were efficacious muscarinic agonists at cortical receptors. All four compounds produced peripherally mediated salivation and centrally mediated hypothermia at doses 50-50,000 fold lower than arecoline. The most potent was L-670,548, the methyl oxadiazole in the 1-azanorbornane series, which had an ED50 of 0.0016 mg/kg on the hypothermia model. This derivative was also the most potent compound in ex vivo binding studies (ED50 0.0069 mg/kg) and showed excellent brain penetration (3.8% of the administered dose). These derivatives are the first non quaternary efficacious agonists which show good penetration into the CNS (central nervous system), and will prove useful tools in understanding the role of muscarinic receptors in CNS function. PMID- 2272361 TI - The anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor subtypes in rat brain: sensitivity to guanine nucleotides. AB - Eltoprazine (DU 28853) inhibits offensive aggressive behaviour in several animal species. We characterized the binding of radiolabelled eltoprazine in rat brain by autoradiography. [3H]Eltoprazine displayed saturable and high-affinity binding to several brain areas, including the basal ganglia, hippocampal formation and cerebral cortex (Kd values ranging from 4.2 to 9.5 nM). The maximal binding capacities (Bmax) for [3H]eltoprazine were similar to those for [3H]5-HT and were highest in the substantia nigra and subiculum. Competition with eltoprazine for [3H]ligand binding to the various 5-HT1 receptor subtypes revealed preferential binding to 5-HT1A (IC50 values ranging from 42 to 50 nM) and 5-HT1B (IC50 values ranging from 25 to 38 nM) recognition sites. The drug had moderate affinity for 5 HT1C sites (IC50 = 282 nM). Addition of GTP or its stable analogue Gpp(NH)p to the radioligand assay caused a marked reduction (50-90%) in both [3H]eltoprazine and [3H]5-HT binding. These effects were substantially less in the choroid plexus. The binding of the antagonist (-)[125I]Iodocyanopindolol ([125I]ICYP) to 5-HT1B recognition sites, as quantified in the subiculum and substantia nigra, was either unaltered or slightly enhanced by the addition of 10(-3) M GTP. Furthermore, GTP did not affect the competition for [125I]ICYP binding by the 5 HT1-antagonist methiothepin, whereas it did significantly reduce the displacement by eltoprazine, resulting in an almost twofold increase in IC50 values. The data indicate that the anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor sites and that this interaction is modulated by guanine nucleotides. PMID- 2272362 TI - Use- and frequency-dependent blockade by UL-FS 49 of the if pacemaker current in sheep cardiac Purkinje fibres. AB - The mechanism by which the bradycardiac agent UL-FS 49 blocks the if pacemaker current was investigated in sheep Purkinje fibres using the two microelectrode voltage-clamp technique. If was activated by 1 s pulses applied between -30 mV and -120 mV at 0.4 Hz in a modified Tyrode solution containing BaCl2 and MnCl2, and with TRIS replacing most of the Na+. UL-FS 49 caused an exponential decline of the if current amplitude during a train of pulses. Both the rate and extent of the if reduction increased with drug concentration, without there being a resting blockade. Recovery from blockade followed a single exponential time course during prolonged hyperpolarizations. The recovery rate was extremely slow and increased with more negative voltages, as did the extent of steady state recovery from blockade. A frequency-dependent reduction of the diastolic depolarization rate resulted from a use-dependent blockade of the pacemaker current. PMID- 2272363 TI - Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U 62,066E, in rats. AB - The effects of highly selective agonists of kappa-opioid receptors, namely U 50,488H and U-62,066E, on the capsaicin-induced cough reflex in rats were studied. Intracisternal (i.cist.) injection of U-50,488H and of U-62,066E significantly decreased the number of coughs in a dose-dependent manner. The antitussive potency of i.cist. injection of these two kappa-opioid agonists was similar to that of morphine. Intraperitoneal (i.p.) injection of U-50,488H and of U-62,066E also decreased the number of coughs, again in a dose-dependent manner. The antitussive effects of U-50,488H and U-62,066E were blocked by norbinaltorphimine, an antagonist of kappa-opioid receptors. Methysergide, administered i.cist. (3 nmol), antagonized the antitussive effects of U-50,488H and U-62,066E. However, ketanserin had no effect on the antitussive effects of these kappa-opioid agonists. These data suggest that U-50,488H and U-62,066E exert their antitussive effect on rats through stimulation of kappa-opioid receptors. Furthermore, with respect to the antitussive effects of kappa-opioid agonists, the system that involves 5-HT1 receptors may be more important than the system that involves 5-HT2 receptors. PMID- 2272364 TI - Antagonism of 5-HT3 receptors attenuates the effects of ethanol on extracellular dopamine. AB - The effect of a 5-HT3 antagonist, ICS 205-930, on ethanol-induced changes in extracellular dopamine, was investigated with in vivo microdialysis. Pretreatment of rats with ICS 205-930 effectively attenuated the subsequent increases in dopamine, in both the nucleus accumbens and corpus striatum. This suggests that 5 HT may be involved in the effects of ethanol on dopaminergic systems. PMID- 2272365 TI - Endothelin-1, but not sarafotoxin s6b, induces cross-desensitization of rat aorta contraction. PMID- 2272366 TI - Intermittent versus continuous neuroleptic treatment in a rat model. AB - The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D2 receptor blocker haloperidol or the combined dopamine D1/D2 receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroleptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our findings are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administrations. PMID- 2272367 TI - Analgesia produced by intrathecal administration of the kappa opioid agonist, U 50,488H, on formalin-evoked cutaneous pain in the rat. AB - The antinociceptive activity of the selective kappa opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test. Three successive i.t. doses of 5, 10 and 35 nmol of U-50,488H produced a gradual reduction of pain scores which was statistically significant at all observation periods. This effect was antagonized significantly by 3 mg/kg i.p. of the opiate antagonists, naloxone and WIN 44,441-3. The analgesia profile showed a clear dose response relationship. A dose producing 50% 'maximum possible analgesia' of 6.20 nmol (95% confidence interval: 3.05-12.59 nmol) was calculated. The results indicated that cutaneous pain of a chemical/inflammatory nature is highly sensitive to activation of kappa receptors of the spinal cord dorsal horn. PMID- 2272368 TI - Multiple sites of action of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+) 3PPP) in blood vessels. AB - Functional effects of the sigma ligand, (+)-3-(3-hydroxyphenyl)-N-(1 propyl)piperidine ((+)-3PPP), were explored in perfused rat tail and rabbit ear arteries in vitro. In the rat tail artery (+)-3PPP inhibited contractile responses to adrenergic nerve stimulation, an effect which was reversed to potentiation by the dopamine D2 receptor antagonist sulpiride. In the rabbit ear artery, however, (+)-3PPP potentiated contractile responses to nerve stimulation, an effect which was unchanged by sulpiride. In the rat tail artery, blockade of norepinephrine uptake by cocaine and deoxycorticosterone in the presence of sulpiride revealed two additional actions of (+)-3PPP. First, an inhibitory action on the monoamine uptake site was confirmed by direct measurement of [3H]norepinephrine accumulation. Second, at higher concentrations, an action to inhibit contractile responses to adrenergic nerve stimulation was manifested at a still unidentified site. These studies demonstrate that the observed functional effect of (+)-3PPP results from its combined actions on three individual sites with the net effect dependent on the relative densities of these different receptor sites in each type of vessel. PMID- 2272369 TI - Electrophysiological effects of monensin, a sodium ionophore, on cardiac Purkinje fibers. AB - Monensin, a monovalent cation ionophore, transports sodium ions preferentially. We found that, in the cardiac Purkinje fibers, monensin 10(-5) M increased the resting tension of the fiber bundle in Tyrode solution containing 4.5 mM Ca. This ionophore (10(-5) M) shortened the duration of the action potential and suppressed the pacemaker potential. In Na-free or Ca-free solutions, monensin had no effect on the configuration of the action potential. In voltage clamp experiments, monensin 10(-5) M shifted the holding current at -40 mV outwardly, increased the instantaneous inward current (possibly inward rectifying potassium current, IK1) and increased the transient outward current (Ito), whereas it attenuated the hyperpolarization-activated inward current (If). The delayed rectifying outward current (IK) was not significantly affected by monensin 10(-5) M. The transient inward current (ITI) appeared in the presence of monensin 10(-5) M. These changes induced by monensin are consistent with changes in configuration of the action potential induced by monensin. The membrane current changes are considered to be induced by an increase in intracellular Ca concentration, probably via a Na-Ca exchange following an increase in intracellular Na concentration, and by alteration of intra- and extracellular Na and K concentrations. PMID- 2272370 TI - Differential venous effects of isoprenaline in conscious rats. AB - The role beta-adrenoceptors in the control of venous tone is not clear. This study examines the dose-response effects of isoprenaline, a non-selective beta adrenoceptor agonist, on mean circulatory filling pressure (MCFP), an index of body venous tone, in conscious and unrestrained rats. Dose-response curves of isoprenaline were constructed in three groups of rats, namely, I, intact; III, pretreated with the ganglionic blocker hexamethonium; and V, pretreated with noradrenaline. Three additional groups, Groups II, IV and VI, served as time controls and were treated similar to I, III and V, respectively, except that they were given normal saline in place of isoprenaline. The infusion of isoprenaline in intact rats dose dependently decreased mean arterial pressure (MAP) and increased heart rate (HR) and MCFP while in the ganglionic-blocked rat, it caused similar effects on MAP and HR but had no significant effects on MCFP. In rats given noradrenaline, isoprenaline again decreased MAP and increased HR and, in contrast to the other two groups, it decreased MCFP. The results show that isoprenaline has variable venous effects depending on existing venous tone. It causes reflex-mediated venoconstriction under normal conditions due to its hypotensive effects and direct venodilatation when venous tone is elevated by the infusion of noradrenaline. PMID- 2272371 TI - The coexistence of adenosine A1 and A2 receptors in guinea-pig aorta. AB - The effects of adenosine, 5'-(N-ethyl)carboxamidoadenosine (NECA), 2 chloroadenosine (2-CA), N6-cyclohexyladenosine (CHA) and N6(R-2-phenylisopropyl) adenosine (R-PIA) on the tone of phenylephrine-constricted guinea-pig isolated aorta have been examined. For aortic relaxation the analogues exhibited the following rank order of potency: NECA greater than adenosine greater than 2-CA greater than R-PIA greater than CHA. This is consistent with previous reports that relaxation of this tissue is mediated by the adenosine A2 receptor. An unexpected finding was that R-PIA, 2-CA and CHA all induced contractions at concentrations lower than were required for relaxation, giving a biphasic dose response curve. Neither NECA nor adenosine contracted the aorta. This is consistent with activation of vascular A1 receptors. An A1-selective concentration of the antagonist 1,3-dipropyl-8-cyclopentyl xanthine abolished the contraction elicited by R-PIA in the guinea-pig aorta. This further suggests that the contraction is mediated by A1 receptors. PMID- 2272372 TI - Reactivity of guinea-pig isolated trachea to methacholine, histamine and isoproterenol applied serosally versus mucosally. AB - Guinea-pig tracheas were perfused with recirculating modified Krebs-Henseleit solution while monitoring changes in inflow-outflow pressure difference, which is an index of trachealis muscle tone. The reactivities of the trachealis muscle to methacholine, histamine and isoproterenol applied separately to the mucosal (intraluminal, IL) or serosal (extraluminal, EL) compartments were compared, and evidence for the agonist-induced release of epithelium-derived relaxing factor (EpDRF) was sought. All agents were more potent when added to the EL compartment, but the IL/EL EC50 ratios were different: 100 for methacholine, 41 for histamine and 25 for isoproterenol. Methacholine or histamine added to the IL compartment, after the preparations were pre-contracted with the same concentration of the agonist or 30 mM KCl added EL, did not result in relaxation. Likewise, IL isoproterenol did not evoke contraction. IL KCl evoked relaxation. The results indicate that the epithelium reduces access of bronchoactive agents to the muscle, while an immediate relaxant effect of EpDRF released by agonists could not be demonstrated. PMID- 2272373 TI - Pharmacological properties of contraction caused by sodium removal in muscle strips isolated from canine coronary artery. AB - Contractions produced by Na+ removal were studied in muscle strips isolated from canine coronary artery. In the presence of 20 mM K+ and 0.5 mM Ca2+, rapid contractions were observed repeatedly on complete replacement of NaCl with sucrose. This contraction in the absence of Na+ (0-Na) was not affected by phentolamine but was strongly inhibited by verapamil. Ouabain slowly potentiated the O-Na contraction and markedly reduced the inhibition due to verapamil. The O Na contraction was dependent on external Ca2+ both with and without ouabain. Bepridil had effects very similar to those of verapamil. Amiloride and excess Mg2+ reduced the O-Na contraction and the degree of their inhibition was similar after ouabain treatment. The decrease in verapamil susceptibility could suggest that the O-Na contraction has verapamil-sensitive and -insensitive components. The former is probably due to Ca2+ influx through voltage-dependent channels and the latter to Ca2+ influx through an Na(+)-Ca2+ exchange process. Ouabain is considered to increase the contribution of Na(+)-Ca2+ exchange to the O-Na contraction. Mg2+ may inhibit both verapamil-sensitive and -insensitive pathways. Amiloride probably exerts its inhibitory effect on the contractile machinery. PMID- 2272374 TI - Endothelin: a potential modulator of cerebral vasospasm. AB - 1-(5-Isoquinolinesulfonyl)-homopiperazine, HA1077, is a calcium antagonist with anti-vasospastic properties. This compound blocks intracellular actions of calcium in a variety of experiments. In the present study, we examined the effects of HA1077 on the vascular actions of endothelin, an endothelium-derived vasoactive peptide, in dogs in vitro and in vivo. Intracisternal injections of endothelin (0.01 nmol) produced a significant vasospasm, as measured by angiography, similar to that seen in the canine hemorrhage model. Infusion of HA1077 led to a significant dilatation of the spastic basilar artery in endothelin-treated dogs. The rank order of in vitro contractile activity in canine cerebral arteries was a stable thromboxane A2 analog greater than endothelin greater than 5-hydroxytryptamine greater than prostaglandin F2 alpha greater than histamine greater than noradrenaline. HA1077 effectively antagonized the endothelin-induced contraction of canine basilar arterial strips in both calcium-containing and calcium-free medium. The present results indicate that HA1077 is an effective antagonist for endothelin in vitro and in vivo. PMID- 2272375 TI - Mechanisms of pinacidil-induced vasodilatation. AB - The mechanism of the vasodilator effect of pinacidil was examined. Pinacidil (0.1 100 microM) inhibited the increases in cytosolic Ca2+ ([Ca2+]i) and muscle tension due to norepinephrine in rat aorta. In contrast, a Ca2+ channel blocker, verapamil, inhibited the norepinephrine-stimulated [Ca2+]i more strongly than the contraction. Higher concentrations of pinacidil (3-100 microM) inhibited the verapamil-insensitive portion of the contraction and [Ca2+]i. An inhibitor of ATP sensitive K+ channels, glibenclamide, antagonized the inhibitory effect of low concentrations (less than or equal to 10 microM) of pinacidol. Pinacidil did not change the contraction induced by Ca2+ in vascular smooth muscle permeabilized with Staphylococcus aureus alpha-toxin. Norepinephrine (in the presence of GTP), 12-deoxyphorbol 13-isobutyrate (in the absence of GTP), and treatment with GTP gamma S potentiated the contraction of permeabilized smooth muscle induced by the addition of Ca2+. Pinacidil (100 microM) inhibited the potentiation due to GTP gamma S or norepinephrine but not to phorbol ester. These results suggest that pinacidil has dual effects on vascular smooth muscle contraction. At lower concentrations (greater than 0.1 microM), it decreases [Ca2+]i, possibly by activating ATP-sensitive K+ channels. At higher concentrations (greater than 3 microM), it may additionally inhibit the receptor-mediated, GTP-binding protein coupled phosphatidyl inositol turnover. PMID- 2272377 TI - HIV rates among U.S. teenagers. PMID- 2272376 TI - Physiological release of nitric oxide is dependent on the level of vascular tone. AB - The pressor effect of NG-methyl-L-arginine (NMA) was tested in urethane anesthetized rats which were untreated (control) or devoid of sympathetic tone. In contrast with controls, the NMA response was attenuated by pithing or ganglionic blockade. In pithed rats, the induction of moderate or intense vasoconstriction with constant phenylephrine infusion restored or augmented, respectively, the NMA pressor response. Our data suggest that vascular tone may physiologically regulate the release of nitric oxide in vivo. PMID- 2272378 TI - Contraceptive practice in the United States, 1982-1988. AB - Use of oral contraceptives by married women declined markedly between 1973 and 1982, but analysis of data from the 1988 National Survey of Family Growth shows that this decline stopped between 1982 and 1988. Reliance on female sterilization continued to increase, however, and it remained the leading method among currently married and formerly married women. Among women of all marital statuses, IUD use dropped by two-thirds between 1982 and 1988, from 2.2 million to 0.7 million women. As the proportion of less-educated, low-income, black and Hispanic contraceptive users choosing the IUD decreased, the proportion relying on female sterilization increased. Among college-educated white women, use of female sterilization did not increase; instead, pill use rose in this group. Condom use increased most sharply among teenagers and rose among never-married white and black women, but the pill was still the leading method by far in these groups, regardless of race. Among never-married black women, reliance on sterilization increased significantly between 1982 and 1988, with female sterilization becoming the second leading method. Use of the diaphragm declined sharply over the same period among never-married white women and among those who intended to have more children, as did use of periodic abstinence (rhythm and natural family planning) and foam. PMID- 2272379 TI - The sexual and reproductive behavior of American women, 1982-1988. AB - Comparison of 1988 data from the National Survey of Family Growth with 1982 data reveals that the proportion of U.S. women who have had sexual intercourse rose slightly, from 86 percent to 89 percent. Among teenagers, the proportion sexually active rose from 47 percent to 53 percent; most of the change is attributable to increases occurring among white and nonpoor teenagers, thus narrowing racial and income differences. Among women aged 15-44 in 1988 who have ever had intercourse, 67 percent reported that they had had two or more sexual partners in their lifetime. The proportion was highest among women aged 20-34 (about 70 percent), but 58 percent of sexually active teenage women reported having had two or more sexual partners. About 67 percent of women of reproductive age in 1988 were exposed to the risk of unintended pregnancy, up from 63 percent in 1982. Among these women, 35 percent rely on contraceptive sterilization to prevent pregnancy and 55 percent use reversible methods, while 10 percent use no method. Poor women are much more likely than nonpoor women to be using no method of contraception (15 vs. eight percent); among poor teenagers, this proportion reaches 25 percent. The level of contraceptive use at first intercourse among teenage women improved substantially between 1982 and 1988, however, rising from 48 percent to 65 percent. During 1984-1988, almost four in 10 births and almost six in 10 pregnancies among American women were unintended; most of these were mistimed, but 12 percent of births were unwanted ever.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272380 TI - Barriers to prenatal care among low-income women in New York City. AB - Postpartum in-hospital interviews with 496 low-income women in New York City revealed that attitudinal and motivational barriers as well as financial obstacles are significant impediments to timely initiation of prenatal care. The two most common reasons cited by these women in explaining why they had obtained prenatal care late or not at all were motivational items: "feeling depressed and not up to going for care" and "needing time and energy to deal with other problems." In logistic regression analyses, receipt of late or no prenatal care was significantly associated with the latter motivational barrier, along with the cost of care, having no health insurance, being Hispanic, being a substance abuser and holding negative attitudes toward the use of prenatal care. PMID- 2272381 TI - Patterns of adult male coresidence among young children of adolescent mothers. AB - This article uses data from the National Longitudinal Survey of Youth to examine the coresidence patterns of children and adult males during the first three years of a child's life, with special attention to the children of adolescent mothers. Overall, the most common experience was for the children to have an adult male present over the full period. However, there were differences by race and the mother's age when she gave birth. For example, 83 percent of white children and 47 percent of black children born to mothers aged 20 or older lived with an adult male during their entire early childhood, while three quarters of white children and fewer than one-third of black children born to mothers younger than 18 had a male present in their household over their first three years. Among both races, children of older mothers were significantly more likely than others to be born into a household where an adult male was present. The stability of male coresidence varied significantly by the mother's age among white children, but not among blacks. Overall, black children experienced more changes in male coresidence than whites. Finally, the likelihood that the adult male would be married to the mother was positively associated with white race and the age of the mother when she gave birth. PMID- 2272382 TI - Funding restrictions on fetal research: the implications for science and health. PMID- 2272383 TI - Freedom of choice. PMID- 2272384 TI - On computing failure rates. PMID- 2272385 TI - [Approaches to the experimental prolongation of life]. AB - Modern approaches to lifespan prolongation of laboratory animals are considered. Calorie-deficient diet increasing lifespan, leads to essential hormonal shifts, to changes in the activity of genome, protein biosynthesis. These mechanisms determine lifespan prolongation. PMID- 2272386 TI - [Effect of carbohydrate-enriched diet and subsequent food restriction on life prolongation in Fischer 344 male rats]. AB - Increased proportion of carbohydrates (dextrin) in the diet has a life prolonging effect upon male Fischer 344 rats; however, the effect of this diet appears only when the rats aged from 6 weeks to 6 months are on diet, after this treatment median survival of experimental animals increases by 96 days and the 10th percentile increases on the average by 10 days (n-60). Further maintenance of animals on the same diet has minimum effect: animals being on this diet throughout the whole life exhibit a median lifespan increase by 120 days and an increase in the 10th percentile by 41 days. However, if such animals aged 6 months are transferred to a restricted (60%) food intake regimen (control diet, not enriched with carbohydrate) a further increase in median and 10th percentile lifespan prolongation can be observed reaching 328 and 396 days, respectively as compared to controls. The effects of this early feeding (from 6 weeks to 6 months) with a carbohydrate-enriched diet available ad libitum and food restricted (60% controls) regimen fed from the age of 6 months onwards are additive, the final results being identical as if the animals are kept on the 60% food restricted intake throughout the whole life. PMID- 2272387 TI - [Mechanism of thymic involution (analysis of intrinsic and extrinsic aspects)]. AB - The mechanisms of thymic involution with age are analyzed in terms of both intrinsic and extrinsic aspects. The intrinsic factors include: decrease in the number of thymocyte-precursors (pro-T cells) in the bone marrow, in emigration of pro-T cells into the thymus, in proliferation of thymic lymphocytes and decrease in extrathymic factors promoting proliferation of thymic lymphocytes. The extrinsic factors capable to exert modulating effects on the thymic function are humoral factors of the hypothalamic-pituitary origin. It seems much easier to manipulate the extrinsic factors by controlling neuro-endocrine stimulation, and to restore the thymic involution. This is quite encouraging, because it permits restoring the impaired immune functions of the aged people. PMID- 2272388 TI - [Influence of the recipient's age on the effect of transplanting lymphoid organs from newborn donors]. AB - The development of immunological capacity of newborn thymus and spleen grafted under the kidney capsule of different-age recipients was investigated. The grafts functions appear to depend strongly upon the macroenvironment of the organism where their development occurs. Therefore+ the favourable influence of young environmental factors, gradually decreasing with the recipient age to become immunosuppressive in old animals is obtained. These data indicate a predominant significance of the macroenvironmental factors both in maturation of the immune system and its alteration during aging. PMID- 2272389 TI - [Genoregulatory mechanisms of aging as a basis for the development of age-related pathology]. AB - The development of age pathology has been studied in relation to changes occurring in the activity of various genes and in the synthesis of various proteins as well as in relation to the topography of those changes. The relationship between age-related changes in the activity of various genes and the onset of atherosclerosis, cancer, diabetes, Parkinson's disease and Alzheimer's disease has been studied. The appearance of gene regulatory age-related changes in cells of the nervous, endocrine and immune systems determines their involvement in the age pathology development. The prospects of gene regulatory therapy aimed at selective activation and suppression of various gene groups are outlined. PMID- 2272390 TI - [Proliferative and differentiation properties of bone marrow hematopoietic stem cells in CBA mice of various ages]. AB - Hemopoietic bone marrow stem cells (CFCs) of young (3-5 months) and old (23-24 months) were studied according to their ability to form colonies in spleens of the lethally irradiated animals. The number, morphology and volume of CFCs were microscopically examined. The content of CFCs remained unchanged during aging. The number of erythroid colonies decreased in old mice, while that of granulocyte macrophage and mixed colonies did not change. The megakaryocyte colonies showed even an increase with age. Volumes of all the colony types, except megakaryocyte, reduced. The results obtained thus reflect some age-related features of early stages of the stem-cell differentiation. PMID- 2272391 TI - [Uptake and K+-evoked release of 3H-norepinephrine in the mesodiencephalic synaptosomes of albino rats during aging. Role of N-acetyl-L-aspartic acid]. AB - The uptake and K(+)-evoked (40 mM) release of 3H-norepinephrine (3H-NE) in mesodiencephalic synaptosomes of adult and senescent rats and the effect of N acetylaspartic acid (NAA) on these processes have been studied. It has been shown that the uptake of 3H-NE by old rats is reduced considerably. The K(+)-evoked release of 3H-NE from rats synaptosomes is significantly decreased in aged rats. In the presence of 10(-4)-3.10(-3) M NAA the uptake of 3H-NE by adult and senescent rats synaptosomes remains unchanged. In these concentrations NAA inhibits the K(+)-evoked release of 3H-NE from synaptosomes of adult rats, but it exerts no effect on this process in senescent rats. PMID- 2272392 TI - [Prospects for research on the modulation of gene activity during brain aging]. AB - This brief review is concerned with prospects of the role of modulated gene expression in the brain during aging and in two age-related neurological diseases: Parkinson's and Alzheimer's diseases. Two key mechanisms involved in the disturbance of neuronal function during aging, i. e. deafferentation syndromes (as a result of the impairment of afferent influences) and steroid induced neuronal changes, have been studied. The author suspects that many aspects of cell aging in the brain represent the influence of the environmental factors. The conception of new therapeutic approaches to the treatment of Alzheimer's disease has been developed. PMID- 2272393 TI - [Central mechanisms of the development of motor disorders during human aging]. AB - This paper deals with the functional state of the brain and its descending regulatory influences on the brain stem-spinal formations in the elderly. The role of changes revealed in the formation of the clinical syndrome of age-related extrapyramidal insufficiency (EPI) as a risk factor of Parkinson's disease, has been shown. 274 apparently healthy subjects aged from 20 to 102 and 136 patients with early stages of Parkinson's disease were examined. The program of the neurophysiological investigation included: frequency-integrative analysis of EEG, visual and somatosensory potentials, simple motor reaction time and stimulating electroneuromyography (H reflex). It has been found that in aging and in Parkinson's disease one-directional changes in the CNS function that form age related and pathologic EPI occur. The complex of neurophysiological indices is a reflection of the CNS influence on the underlying spinal formations, and it can be used for early diagnostics of the motor disorders in aging. PMID- 2272394 TI - [Role of the neuroendocrine system in aging]. AB - The study involves 3 aspects of neuroendocrine control over the organism functions in aging: the decline in reproductive functions, the reduction of growth hormone secretion and the decrease in thymic functional activity and the altered relationship between neuroendocrine and immune systems. The role that an age-related decrease in dopamine and noradrenaline production by hypothalamic neurones plays in the above age changes in neuroendocrine control has been traced. The age-related decrease in functions of hypothalamic catecholaminergic neurones is apparently caused by the damaging effect of hormones (prolactin, glucocorticoids and, especially, estrogen), free radicals and toxins, both of the endogenous and exogenous origin. The restrained nutrition increases lifespan of the experimental animal owing to reduced "wear out" of the neuroendocrine system and organs and tissues that are controlled by this system. PMID- 2272395 TI - [Biological manifestations of the andropause]. AB - Aging in men is accompanied by signs of decreased virility and fertility: testicular volume, muscle mass, pilosity, sexual activity, daily production of spermatozoa, plasma testosterone levels, the number of Leydig cells and blood supply of the testicles decrease significantly with age. The pulsatility of LH levels in young and elderly men has been studied by taking plasma samples with an interval of 10 minutes for 12 hours. Age alterations at the hypothalamic pituitary levels of testosterone production and an increase in gonadostat sensitivity to hormonal influences realized via the feedback mechanism are found. Whenever androgen therapy of eugonadal elderly men is considered, a sufficient dosage should be administered, as otherwise, due to the feedback effects, administered androgens, suppressing endogenous secretion might not increase plasma-testosterone levels. Changes in neurotransmitters and neuromodulators play a determinant role in the sexual behaviour of elderly men. PMID- 2272396 TI - [Sympathetic regulation of adrenal medullary function during aging]. AB - Our recent studies on changes in sympathoadrenal medullary function with age in anesthetized Wistar rats were reviewed. Although secretion rates of adrenaline and noradrenaline from the adrenal gland under resting conditions varied among animals, they gradually increased after 300 days and reached a level 2-4 times higher at 800-900 days compared with that of 100 days. Spontaneous activity of a single sympathetic nerve fiber under resting conditions also increased during aging in a manner similar to the catecholamine secretion rates. Reflex responses of mass activity of adrenal sympathetic nerve fibers to stimulation of baroreceptor and cutaneous mechanoreceptors were compared in young adult (4 months old) and aged (26 months old) Wistar rats under strictly controlled conditions for anesthesia, respiration and body temperature. Under these conditions the reflex depression in response to baroreceptor stimulation and cutaneous brushing as well as reflex excitation in response to cutaneous pinching were quite well maintained in the aged rats. PMID- 2272397 TI - [Modification of the Adams surgical method in craniofacial fractures]. PMID- 2272398 TI - [Oral surgical aspects of benign symmetrical lipomatosis]. PMID- 2272399 TI - [Microscopic study of hammered gold filling sections]. PMID- 2272400 TI - [Evaluation of comfort, sound formation and food relations of the oral surface of mould cast metal plates, based on patient questionnaires]. AB - Comfort, sound formation and food relations of the oral surface of mould cast metal plates have been examined by means of interrogatory examination. From processing the answers of the 14 examination persons it has turned out that in view of the examined aspects the smooth oral surface is more favourable than the meshy one. On basis hereof the employment of the smooth surface is suggested. PMID- 2272401 TI - [Significance and possibilities of removing the debris layer forming during root canal therapy (review of the literature)]. AB - The clinical estimation of the "Debris Layer" forming in the course of expanding the root channel is not entirely uniform in the literature wherefore also the question of its removal is the subject of dispute. Also the variety of methods suggested for stopping the DL proves that, for the time being, there is no optimum method yet and further research is still necessary. PMID- 2272402 TI - Mesenchymal-epithelial cell interactions in the ovary: estrogen-induced theca cell steroidogenesis. AB - The role of mesenchymal-epithelial cell interactions in the control of ovarian physiology was investigated Theca cells are the mesenchymal (i.e. stromal) like cells that surround the ovarian follicle and produce androgen in response to the gonadotropin luteinizing hormone (LH). Granulosa cells are the epithelial-like cells that form the follicle, support the developing oocyte, and utilize androgens produced by theca cells as a substrate for the production of estrogen Observations presented indicate that estrogen produced by granulosa cells dramatically stimulates androgen production by theca cells Estrogen was found to have greater stimulatory effect on theca cell androgen production than gonadotropin, and a combination of estrogen and gonadotropin results in a greater than additive response of the two hormones. Regulation of androgen production by estrogen provides a local feedback loop in the follicle that will significantly influence ovarian steroidogenesis. This steroid-mediated theca-granulosa cell interaction provides evidence for the importance of mesenchymal (i.e. stromal) epithelial cell interactions in adult tissues and implies that epithelial cells can produce paracrine factors that modulate mesenchymal cell function and differentiation. The theca cell-granulosa cell interaction identified is postulated to be a critical mesenchymal-epithelial cell interaction for the control of ovarian physiology and the endocrine status of the female. PMID- 2272403 TI - Human relaxin inhibits division but not differentiation of 3T3-L1 cells. AB - For the first time, we demonstrate here the ability of human relaxin to block cell division. During the induction of differentiation of 3T3-L1 fibroblasts to adipocytes, the cells typically undergo two rounds of cell division followed by accumulation of lipid droplets and expression of insulin-stimulated glucose transport as the cells attain the adipocyte phenotype. Human relaxin added during induction had no effect on the development of the adipocyte phenotype or insulin stimulated glucose transport. However, it blocked cell division at a half-maximal concentration of 1.25 nM, well within physiological range. This could be reversed by the addition of antibodies specific for human relaxin. Thus relaxin joins a select number of hormones with growth inhibitory properties such as transforming growth factor-beta (TGF beta) and mammastatin. Potentially, this is an important but until now unidentified function of relaxin. Unlike other inhibitory polypeptides, like TGF beta, relaxin does not prevent differentiation but rather uncouples it from cell division. PMID- 2272404 TI - The effect of multiple reminders on long-term retention in human infants. AB - The present series of experiments compared the effects of single- and multiple reminder procedures on the long-term memory of 3-month-old human infants. Subjects were trained in the mobile conjugate reinforcement paradigm, and the reminder treatment was a brief, noncontingent exposure to the moving mobile. In Experiment 1, independent groups received one or two reminder treatments during the 3 weeks following the conclusion of training. Independent groups were tested 1, 3, 7, 14, or 22 days following the last (or only) reminder (i.e., 21-42 days after the end of training). Although retention was equivalent 1 day after one or two reminder treatments, subsequent retention was significantly prolonged by the second reminder treatment: infants receiving a single reminder treatment demonstrated no evidence of retention 7 days after the reminder, but infants receiving two reminder treatments demonstrated perfect retention as long as 14 days later. In Experiment 2, retention was observed 14 days after two reminder treatments irrespective of whether the treatments were presented during the first and second or the third and fourth weeks following the conclusion of training. In Experiment 3, the effect of three reminder treatments on retention was examined. Although retention was excellent when infants were tested 1 day after the third reminder, retention after longer intervals was no better than that observed after a single reminder treatment. PMID- 2272406 TI - Weaning in rats: II. Pup behavior patterns. AB - In this study, litters of rat pups and their mothers were continuously video monitored from Day 14 to Day 35 postpartum in order to describe the behavioral changes that occur during that period. Prior to the onset of solid food intake (Day 18), pups spent most of their active time suckling. During Days 18 to 26, feeding, drinking, grooming, and play-fighting rapidly became frequent daily activities, while suckling gradually began to decline. By Day 28, pups' food and water intake relative to body weight and time allocated to the new behaviors reached asymptote. Pups nevertheless continued to suckle until Day 34. These results suggest that (1) the transition from milk to solid food is embedded in a multitude of behavioral changes; (2) these behavioral changes have distinct temporal characteristics; and (3) the developmental period between Days 14 and 34 can be divided into three phases. PMID- 2272405 TI - Weaning in rats: I. Maternal behavior. AB - Maternal behavior during the weaning period (postpartum Days 14-35) was described from continuous timelapse videorecordings of Norway rat dams and their litters. Time spent nursing declined steadily after Day 20 but persisted until Day 34, about a week longer than suggested by reports of milk transfer. Most of the decline in nursing was due to progressively fewer nursing bouts per day; milk letdowns per day were consequently diminished. Although a private feeding chamber was available to the dams, they did not use this chamber to spend more time away from the pups as weaning progressed. Instead, the dams remained with the pups in the nesting chamber but devoted increasingly less time to nursing. Subtle, progressive changes in maternal behavior are closely orchestrated and coordinated with pup development. PMID- 2272407 TI - Control of intake by human-milk-fed infants: relationships between feeding size and interval. AB - Diurnal feeding behavior of 24 exclusively breast-fed infants was examined at 2, 4, 6, 8, and 12 weeks to assess whether milk intake at a feeding was related to previous (preprandial) or subsequent (postprandial) intervals between feedings. Amount of human milk consumed per feeding and intervals between feedings were measured over a 72-hr period. Correlation analyses revealed that volume of milk ingested at a feeding (meal size) was positively related to preprandial interval at all 5 ages (r = 0.39-0.47, p less than 0.0001). Meal size was likewise related, but not as strongly, to postprandial interval at 4 of the 5 time points examined (r = 0.17-0.25, p less than 0.01). Results of the correlational analyses revealed clear, consistent preprandial correlations, providing evidence for a reactive type feeding pattern among the solely breast-fed infants. Postprandial correlations, possibly reflect an anticipatory feeding pattern, were present but remained consistently low over the 3 months examined, providing little evidence of a developmental shift. This study provides a preliminary foundation for future longitudinal studies that address the regulation of food intake among infants. PMID- 2272408 TI - Nest temperature: effects on maternal behavior, pup development, and interactions with handling. AB - These studies compared the patterns of mother-young contact under different thermal environments and assessed the implications of the differing patterns of contact for pup development and the dam's behavior. In the first experiment, the warm surface dramatically reduced the total amount of contact time between dams and litters and the dam's food intake, but the effects on the pups were limited to smaller adrenal glands. A replication of the first experiment in which daily weighing and handling of the pups was eliminated produced no differences in development. In a third experiment, during which dams had access to a warm surface outside of the next area and the daily weighing and handling was resumed, the pups showed smaller adrenal glands, lower body temperatures and less thermoregulatory ability. A comparison of results suggests that handling increased the weight of adrenal glands of pups reared under the unmanipulated condition, but not the warm-rearing condition. PMID- 2272409 TI - Acute ethanol contamination of the amniotic fluid during gestational day 21: postnatal changes in alcohol responsiveness in rats. AB - Two experiments investigated the effects of an acute alcohol prenatal experience during gestational Day 21 in the rat. At postnatal Days 8 and 9, this experience was sufficient to significantly increase ethanol odor preference as well as alcohol intake. Fetuses treated with a nonethanol stimulus (lemon) also exhibited changes suggesting increased lemon olfactory acceptance patterns (Exp. 1). Furthermore, when the olfactory component of the solutions experienced in utero were later paired with a novel tactile cue, responsiveness to such cue was strongly affected. Pups prenatally exposed to alcohol exhibited significantly lower tactile preference scores when texture was postnatally paired with ethanol odor when compared to specific controls. This effect was also observed in lemon treated subjects after pairing defined by lemon-texture trials (Exp. 2). The results reported in alcohol-treated subjects appear not to be related with postabsorptive effects of the drug. It is suggested that sensory prenatal experience with alcohol is responsible for the reported changes in postnatal alcohol responsiveness patterns. PMID- 2272410 TI - Experimentally induced murine rhabdomyosarcomas--correlation between cellular contacts, matrix formation and cellular differentiation. AB - Rhabdomyosarcomas (RMSs) consist of a mixture of primitive mesenchymal cells as well as cells showing various stages of rhabdomyomatous differentiation. The qualitative and quantitative degree of the rhabdomyomatous differentiation of the cells, evaluated by their morphology and expression of defined structural and functional proteins, is accepted as the basis of diagnosis and is considered to be related to the biological behaviour of RMSs. Therefore we investigated solid experimentally induced murine RMSs, adherent (subconfluent, confluent) cell cultures obtained therefrom, and also suspension cultures and studied the expression of muscular differentiation markers (vimentin, desmin, myoglobin) and the formation of extracellular matrix components (fibronectin, laminin). When we compared solid tumours with adherent cell cultures of decreasing cell densities (confluent up to single cells) and with cells grown in suspension, we found a gradual decline of differentiation ("dedifferentiation"). This decline paralleled the decrease of cell-cell and cell-substrate contacts. In suspension cultures, cells were prevented from interacting with each other and the substratum, no rhabdomyomatous differentiation of the cells took place. If restoration of cellular contacts was allowed, either by adherent growth or by reinoculation into nude mice, the process of dedifferentiation was completely reversible. Consequently, it was demonstrated that the increase of cell-cell and cell substrate contacts was strongly associated with the appearance or increasing expression of the desmin intermediate filament cytoskeleton and with formation of the extracellular matrix components fibronectin and laminin. The microfilament (F actin) system was modulated from an impressive stress-fiber system in subconfluent to a dense network in confluent monolayers. The extent of cell substrate contacts, mediated by extracellular matrix components, and the number of cell-cell interactions are responsible for the capability of a malignant mesenchymal cell, which is able to undergo rhabdomyomatous differentiation, to achieve the various stages of maturation. PMID- 2272411 TI - Formation of chondrous and osseous tissues in micromass cultures of rat frontonasal and mandibular ectomesenchyme. AB - Rat frontonasal and mandibular mesenchyme was isolated from day-12 1/2 (stage-22) rat embryos and cultured at high density for up to 12 days. The stage chosen was based on the observation that mandibular mesenchyme at this stage became independent of its epithelium with respect to the production of both cartilage and bone. Frontonasal cultures developed aggregates of anastomosing columns of cells within 2 days. These grew as the cells enlarged, laying down an Alcian-blue positive matrix by day 3 of culture. Significant mineral was detected by von Kossa staining by day 5 at which time the aggregates covered a large portion of the culture, eventually covering the entire micromass by day 10-12. Mandibular cultures developed centrally located nodular aggregates by 3 days of culture. These nodules increased in number, spreading outwards as the cells enlarged, laying down an Alcian-blue-positive matrix by day 4 and mineral by days 6-7. At this time the nodules began to elongate and coalesce, but never covered the entire culture over the 12-day period. Antibody staining revealed that in both cultures the cells were initially positive for type I collagen. Subsequently, the aggregates began expressing type II collagen, followed by type X, which coincided with the onset of mineralization. At this time some cells were negative for these cartilage markers, but positive for osteoblast markers, bone sialoprotein II, osteocalcin and type I collagen. In addition osteonectin and alkaline phosphatase were demonstrable in all of the aggregate cells late in the culture period. This provided clear evidence that chondroblast and osteoblast differentiation was proceeding within these cultures. The culture of rat facial mesenchyme should prove very useful, not only for the analysis of bone and cartilage induction and lineage relationships, but also in furthering our knowledge of craniofacial differentiation, growth and pattern formation by extending our analysis to a mammalian system. PMID- 2272412 TI - Regulation of alkaline phosphatase and alpha 2(I) procollagen synthesis during early intramembranous bone formation in the rat mandible. AB - We have studied intramembranous bone formation in the developing rat mandible. In this system discrete developmental stages can be readily distinguished: mesenchymal condensation, osteoid deposition, and mineralization. In mandibles of 14-day rat embryos avascular condensed mesenchymal cells can be discerned in a region lateral to Meckel's cartilage and anterior to the first molar bud. In 18 day embryos primary bone structures with mineral deposition are evident, and at 2 days postnatally the mandible is extensively mineralized. In the developing mandible we investigated the pattern of bone/liver/kidney/placenta (BLKP) alkaline phosphatase (ALP) and alpha 2(I) procollagen expression in the differentiating osteoblasts. The level of ALP activity in loose mesenchymal tissue is close to background levels. In contrast, the condensed mesenchymal cells in 14-day embryos, which will subsequently form bone, display intense ALP activity prior to discernible osteoid or mineral deposition. ALP activity in the condensed mesenchymal cells can be inhibited by levamisole, indicating activity of the BLKP gene product. We could not detect a corresponding increase in transcript level for either ALP or alpha 2(I) in the condensed mesenchyme in 14 day embryo using in situ hybridization, probably due to low message abundance. At 18 days, cells throughout the developing mandible express ALP activity, and intense in situ hybridization to BLKP ALP probes is evident in cells lining the developing bone trabeculae. Alpha 2(I) procollagen transcripts have accumulated in cells of the developing mandibular bone, but are not specifically localized to osteoblastic cells. Our results demonstrate that ALP activity is a very early marker of differentiation of cells of the osteogenic lineage, since a marked increase in ALP enzyme activity is clearly detectable in condensed mesenchymal cells prior to osteoid or mineral deposition. In contrast, Wright and Leblond, using the same model system and immunohistochemistry, could not localize type I collagen to preosteoblastic cells surrounding the developing bone trabeculae, and demonstrated localization of type I collagen to osteoblasts bordering developing trabeculae, indicating a substantial increase in type I collagen expression (at least at the protein level) during preosteoblast to osteoblast differentiation. These results indicate a discrete pattern of regulation for both the ALP and alpha 2(I) genes during osteogenic differentiation, which may involve both transcriptional and posttranscriptional regulation. PMID- 2272413 TI - Changes in the composition of cytoskeletal and cytocontractile proteins of rat aortic smooth muscle cells during aging. AB - Cytoskeletal proteins are used as differentiation markers of vascular smooth muscle cells (SMC). To study possible changes in SMC phenotype during aging, cytoskeletal and cytocontractile proteins were quantified in the aortic intima medias of 4-, 12-, 30-, and 36-month-old rats by one- and two-dimensional gel electrophoresis. The percentages of myosin and desmin in total protein decreased with age, while those of actin and vimentin remained unchanged. Immunohistochemical comparison of the aortas from 4- and 30-month-old rats showed that the reduction of desmin reflected a selective disappearance of desmin in some cells. There was an age-related increase in the proportion of beta-actin at the expense of the alpha-isoform. Our results suggest an age-dependent modulation of the phenotype of vascular SMC towards the synthetic state, which is opposite to that observed during developmental differentiation. PMID- 2272414 TI - [Peripartum cardiomyopathy: clinical, echocardiographic and biopsy aspects]. AB - In order to characterize the features of peripartum cardiomyopathy, clinical, echocardiographic and right ventricular endomyocardial bioptic data obtained from 6 patients (pts) (age range: 34.1 +/- 5.5. yrs) who fulfilled peripartum cardiomyopathy diagnostic criteria, were analyzed. Five of these pts had clinical and non-invasive studies for a mean period of 41.6 +/- 59.6 months. All but one were multiparous. Five developed heart failure one month before delivery. Three patients had active myocarditis at endomyocardial biopsy and were treated with immunosuppressive therapy. At follow-up, 3 pts improved by two or three grades of the NYHA functional classification. All 3 showed a reduction in the left ventricular end diastolic diameter (from 3.9 +/- 0.4 to 3.4 +/- 0.3 cm/m2) and a normalization of the shortening fraction in 2 (from 15 to 36% and from 13 to 46% respectively) at echocardiography. These two patients had active myocarditis at the first endomyocardial biopsy. At follow-up, all 3 pts with active myocarditis showed histological evidence of healed myocarditis. In conclusion, peripartum cardiomyopathy is characterized by a high incidence of active myocarditis and improvement seems more frequent in this subgroup of pts. PMID- 2272415 TI - [Color Doppler identification of early diastolic turbulence in the left atrium in patients with mitral valve insufficiency: persistence of regurgitation or inertia phenomenon?]. AB - Color Doppler flow mapping represents the most recent non invasive diagnostic tool for the visualization of intracardiac blood flow. By using the color Doppler flow mapping technique, two independent observers identified the persistence of turbulence in early diastole inside the left atrium in a selected group of 8 patients (3 F and 5 M) with mitral insufficiency. All the patients had moderate or severe mitral insufficiency, due to dilated cardiomyopathy and/or ischemic cardiomyopathy and/or valvular disease. The persistence of early diastolic turbulence inside the left atrium was documented and confirmed by using 30 degrees color sector images, which show the highest possible frame rate. The frame by frame analysis facilitated the identification of two simultaneous flow velocities during early diastole, after the mitral valve was open. The first flow was anterograde and was coded as a red signal; it flowed from the mitral valve into the left ventricle and represented early diastolic left ventricular filling. The second flow was retrograde, and was coded as a blue mosaic signal, due to turbulent aliased jet, extending from the mitral valve into the left atrium, away from the transducer. The interpretation of these two dimensional color Doppler findings is uncertain. We believe, however, that these turbulent velocity signals which persist in early diastole and flow from the mitral valve into the left atrium are probably caused by inertial blood flow due to the impact of regurgitant mitral jets during the previous systole. PMID- 2272416 TI - [The ductus arteriosus in healthy newborn infants studied by continuous Doppler guided by two-dimensional Doppler color echocardiography]. AB - To characterize the ductus arteriosus shunt after birth, 53 normal newborn infants (36-41 weeks gestation), appropriate in size for gestational age, were examined using two dimensional Doppler echocardiography directed continuous Doppler for evidence of patent ductus arteriosus. The infants were examined within six hours of birth, and every six-eight hours thereafter until ductus arteriosus shunt could no longer be detected. In 51/53 infants, an adequate examination was possible and ductus arteriosus was detected in every infant using the standard precordial approach. Using two dimensional Doppler echocardiography a yellow-orange-red jet, sometimes blue in the central area, directed at the lateral wall of the pulmonary artery was recorded; using continuous Doppler a diastolic or continuous spectral flow into the main pulmonary artery was recorded. Ductus arteriosus shunt could no longer be detected in 7 infants 12 hours after birth, in 26 infants 12-24 hours after birth, in 11 infants 24-36 hours after birth, in 5 infants 36-48 hours after birth and in 2 infants 48-60 hours after birth. A diastolic spectral Doppler flow was present in 38 infants and became continuous before duct closure in 27 infants. In 13 infants it was continuous at first examination and until the ductus arteriosus closure. Both diastolic or continuous spectral Doppler flow could present a flat waveform profile, or a protodiastolic or protosystolic peak velocity. The shunt peak velocity increased significantly with the age i.e. (1.5 +/- 0.7 m/sec mean and SD ), at first examination, vs 2.3 +/- 0.6 m/sec at last examination before ductus arteriosus closure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272417 TI - Transesophageal echocardiography in the definition of intracardiac sources of emboli in patients with recent ischemic stroke. AB - Using both transthoracic and transesophageal echocardiography we studied 13 consecutive patients with recent CT-proven ischemic stroke in which a carotid arteries high-resolution ultrasound study failed to detect thrombosis or other relevant atherosclerotic lesions in the pertinent arteries. The mean age was 53 years (range: 36-65). Two patients exhibited clinical signs of cardiac disease at physical examination i.e. absolute arrhythmia, mitral stenosis. Conventional transthoracic echocardiography allowed the detection of potential cardiac sources of emboli in 2/13 patients (15.4%): mitral stenosis in one patient and dilated cardiomyopathy in another. Transesophageal echocardiography was successfully performed without general sedation in all patients. Potential cardiac sources of emboli could be identified in 12/13 patients (92%). Left atrial thrombi were found in 3 patients: in two of them they were associated with rheumatic alterations of mitral valve leaflets; in the third patient a small thrombus was located inside a normal-sized, poorly contracting left atrial appendage. Left atrial appendage could be clearly visualized in all patients. A myxoid degeneration of a prolapsing mitral leaflet was found in 3 patients and an interatrial septum aneurysm in 2. Furthermore, at color-flow Doppler and contrast transesophageal echocardiography, 7 patients (54%) showed patency of the foramen ovale. In 5 of these patients paradoxical right to left shunting after cough or Valsalva manoeuvre could be evidenced. With reference to 11/13 patients with no clinical signs of cardiac disease at physical examination, subclinical potential cardiac sources of emboli could be detected at conventional transthoracic echocardiography in 1 and at transesophageal echocardiography in 10 patients (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272418 TI - [Fontan's operation: results, immediate and long-term postoperative complications]. AB - The Fontan operation and its modifications can be relatively safely performed in the treatment of many complex congenital heart diseases, such as univentricular heart and tricuspid atresia. The main postoperative complications following the Fontan procedure and the incremental risk factors involved in their development are investigated. Between January 1984 and January 1988 eleven patients (6 females and 5 males), ranging in age from 2 to 15 years (mean age: 7.3 +/- 3.7) and in weight from 10.8 to 50 Kg (mean weight 22.3 +/- 12.7) underwent the Fontan operation in our Department. No hospital death occurred. The mean postoperative stay in the Intensive Care Unit was 6.3 +/- 3.9 days. There were two surgical re entries for the same patient: cardiac tamponade (the day of operation) and residual atrial septal defect (2 days following the operation). Eight patients had significant signs of venous stasis, with severe hepatomegaly and pleural effusion. The 11 patients discharged were followed-up for a period of between 3 and 48 months (mean follow-up: 26.4 +/- 18). There were 2 cases of recurrent pleural effusion, 10 to 15 days after discharge. One late death occurred 2 years after the Fontan procedure (massive pulmonary embolism after re-operation). Short and medium-term rate of complications is related to increased post-operative values of mean right atrial pressure (greater than 15 mmHg). Mean right atrial pressures greater than 15 mmHg appear to be correlated with Nakata index values less than 250 mm2/m2. The experience reviewed confirms the excellent results of the Fontan operation, as regards survival and functional recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272419 TI - [Familial pulmonary stenosis: considerations on genetic aspects]. AB - A family with 4 cases of pulmonary valvular stenosis with under-developed or normal right ventricle, is reported. The father and his three daughters were affected. In two of the girls, who were twins, a prenatal diagnosis was made using 2D-echo. The importance of genetic counseling and prenatal diagnosis in the families at risk are underlined. PMID- 2272420 TI - [Initial experiences with laser angioplasty in man: current status, limitations and future possibilities]. PMID- 2272421 TI - [A rare association of aneurysm of the interatrial septum and ventricular tachycardia. Description of 2 cases]. AB - Two patients with isolated atrial septum aneurysm and ventricular tachycardia are reported. In both patients ventricular tachycardia showed left bundle branch block pattern with right axis deviation. The ventricular origin of the arrhythmia was confirmed by electrophysiological study. The aneurysm of the interatrial septum was the only detectable cardiac abnormality. The possible relationship between the atrial abnormality and ventricular tachycardia is discussed. PMID- 2272422 TI - [Right atrial masses: role of two-dimensional echocardiography in indications for emergency surgery. Description of a case of right and left atrial thromboembolism with pulmonary and paradoxical embolism]. AB - Two-dimensional echocardiography is the chosen method for the detection of mobile right atrial masses. In this report we describe a case of pulmonary and paradoxical embolism in which 2D echocardiography was useful for the detection of a thromboembolus entrapped in the patent foramen ovale. The right and left atrial thromboembolus was removed surgically with success. PMID- 2272423 TI - [Post-infarction pseudoaneurysm of the left ventricle as a cause of heart failure. Presentation of a surgically treated case]. AB - Pseudoaneurysm of the left ventricle is an unusual complication of myocardial infarction. Surgical resection is justified by the high risk of rupture. Patients may be asymptomatic, more often a clinical state of chronic heart failure is present. We report on a patient who successfully underwent urgent resection of a large pseudoaneurysm which was the cause of acute heart failure. PMID- 2272424 TI - [Anticoagulants and antiaggregants in ischemic heart disease]. PMID- 2272425 TI - [Oral anticoagulants and antiaggregants in heart valve prostheses]. PMID- 2272426 TI - [Prevention of aortocoronary bypass occlusion]. PMID- 2272427 TI - [Prevention and treatment of left ventricular thrombi]. PMID- 2272428 TI - [Prevention of thromboembolism in arrhythmia]. PMID- 2272429 TI - [Endomyocardial biopsy]. PMID- 2272430 TI - [Principles of physiologic and drug-induced cervix ripening--recent morphologic and biochemical findings]. AB - Maturation of the cervix during pregnancy is an essential pre-requisite for an uncomplicated delivery at term. Physiological cervical ripening is characterised by a diffuse loosening of the collagenous connective tissue with widely scattered collagen fibrils and an increased amount of extracellular ground substance. These morphological changes are similar to those after prostaglandin (PG)-pre-treatment of the cervix. The local application of PG leads to a marked mulifocal loosening of the collagen fibre bundles with "activated" fibroblasts, characterised by a fine granular loosening of the cytoplasm, vacuolised enlarged mitochondria and an increased number of cytoplasmatic vesicles close to the cell surface. In the course of pregnancy the volume of the cervix increases by a significant rise in synthesis of collagen, protein, glycosaminoglycan and fibronectin. The change in consistency during late pregnancy corresponds to a significant decrease in dermatan sulphate coninciding with a marked increase in hyaluronic acid concentration associated with increased water uptake. Contrary to the already published literature, enzymatic collagen degradation does not play an important role in physiological cervical maturation. The action of catabolic enzymes (collagenases, glycosidases), liberated from polymorphonuclear leukocytes invading the extracellular matrix, is responsible for the rapid dilatation of the cervix at parturition. This process is limited by the immediate postpartum insudation of the cervix by plasma containing highly potent proteinase inhibitors (e.g. alpha 2-macroglobulin). PG-induced cervical ripening is associated with a time-limited enzymatic collagen degradation, an increased synthesis of non collagenous proteins and a significant increase in hyaluronic acid concentration. Our basic biochemical findings in cervical ripening and dilatation during parturition may greatly contribute to the development of new concepts in the causal treatment of cervical pathology during pregnancy. PMID- 2272431 TI - [Prevention of HIV infections in surgical gynecology and obstetrics]. AB - In professionally conditioned HIV infections of medical personnel, blood has so far been the only source of infection that is of any importance. Hence, measures to prevent such infections must primarily aim at avoiding any contact with blood from HIV-infected patients. Since the HIV status of the patients and possibly alos other infections transmitted by blood (hepatitis) are often unknown, the following protective measures must be applied in all patients as a matter of routine. Fundamentally, gloves must always be worn when coming into contact with blood, body fluids, mucosa and non-intact skin. In operative procedures and deliveries, barrier methods must be employed to protect the eyes, nose, mouth and skin, as well as technical procedures during surgery and organisational measures to prevent any possible injuries or lesions caused by operative interventions and to reduce the number of persons exposed to risk. So far, needle pricks have been the most frequent mode of infection. Hence, used cannules should be treated with utmost care; do not return them into their protective cover but throw them directly into solid waste containers. After contamination, blood and other body fluids should be eliminated immediately. In case of massive contamination with material containing HIV, chemoprophylaxis should be given careful consideration. PMID- 2272432 TI - [The surgical treatment of ovarian cancer]. AB - Between 1980 and 1988, 350 women suffering from ovarian cancer stage I-IV were admitted to the Department of Gynaecology and Obstetrics of the University of Graz. 320 patients underwent surgery, 174 of 175 with stage III disease, 95 patients had a pelvic lymphadenectomy and 76 both pelvic and para-aortic lymphadenectomy. During the last 4 years, 75% of all patients with stage III disease underwent lymphadenectomy; in 30% the abdomen could be completely cleared of the disease. Bowel resection was necessary in 29% of these patients. After surgery and adjuvant chemotherapy, actuarial 5-year survival was 80% in stage I, 65% in stage II. and 45% in stage III. Lymph node status and amount of residual tumour were the most important factors affecting survival. After pelvic lymphadenectomy 23% patients of stage III showed no evidence of disease (NED) after 5 years. If there was no residual tumour at primary surgery, survival with NED increased to 62% and to 71% in patients with negative pelvic nodes. The data indicates, that pelvic lymphadenectomy improved the 5-year survival of patients with stage II-IV ovarian cancer. PMID- 2272433 TI - [Incidence and prognosis of breast cancer in young women in relation to changes in the risk factor profile]. AB - Trends in breast cancer incidence in women aged 25-44 years are assessed in detail based on data from the population-based cancer registry of Saarland Germany. Compared to 1968-72, from 1978-82 and 1983-87, a highly significant increase in age-standardised incidence by more than 30% was observed. The increase in incidence was most pronounced among women of 25-29 years of age (relative incidence rate 1978-87, compared to 1968-77: 2.03, 95% confidence interval: 1.11-3.71). The role of changes in prevalence of known and suspected risk factors, mainly the age at the onset of menarche, the age at first birth, parity and early and long-term use of oral contraceptives in adolescence, which may partly explain the observed trends, are discussed. The results have important public health implications, such as the need for extended cancer surveillance and epidemiologic research in the Federal Republic of Germany, and offer a quantitative basis for the development and implementation of future early detection programmes as well as the need for medical care facilities. PMID- 2272434 TI - [Significance of the intercostobrachial nerve in axillary lymph node excision]. AB - The anatomy of the intercostobrachial nerves is described; generally two or three of them exist on each side. We followed up 101 modified radical mastectomies with axillary dissection: 53 cases (52.5%) had no sensory disturbances of the intercostobrachial nerves, 48 (47.5%) had either a loss of sensibility or dysesthesias. 8 patients (7.9%) showed an intercostobrachial nerve entrapment syndrome grade I, whereas 4 (3.96%) patients complained of a more intense pain syndrome (2 x grade II, 2 x grade III). PMID- 2272435 TI - [Acute and chronic reduction of diastolic blood flow velocity in fetal umbilical arteries: a Doppler ultrasound study]. AB - The significance of increased placental resistance for the development of fetal distress was examined in 800 pregnant women by pulsed Doppler flow velocimetry of the umbilical arteries. Moderately elevated resistance with reduced diastolic flow velocities with forward flow throughout the diastole, leads to an increased frequency of cesarean section for fetal distress and to a more negative fetal outcome. Severely elevated resistance of the fetal placental circulation shows absent diastolic velocities or even a diastolic reverse flow in the umbilical arteries. In 90% of 25 pregnancies this flow pattern leads to a premature delivery by cesarean section for fetal distress or to intrauterine fetal death. Standardised conditions of the Doppler signal measurement are required, before an absence of diastolic flow velocities is diagnosed. Acute changes in the resistance of the fetoplacental circulation were measured in 6 fetuses showing variable decelerations of the fetal heart rate (FHR). In 3 fetuses the flow curves showed a rapid change from normal to absent and to reverse diastolic flow during a period of time of 20-25 sec, which can indicate an acute resistance and a mechanical occlusion of the umbilical cord. Nevertheless, we found in 2 fetuses variable decelerations without any changes in the flow pattern of the umbilical arteries except for a frequency effect. One fetus showed both types of flow changes. Since two completely different sorts of flow changes exist, we conclude, that umbilical cord compression is not always the cause of variable decelerations of the FHR. PMID- 2272437 TI - [Analysis of the cesarean section rate in 2 clinics with special reference to differences in the patient sample]. AB - Between 1985-87, the total rate of Caesarean sections at the Universitats Frauenklinik, Bern, was considerably higher than at the "Kantonales Spital Sursee" (21.1% vs. 8%). A method to analyse the patient population according to parameters, which are likely to influence the section rate, such as birth weight, parity, foetal position, multiple births and placental pathology, is described. After correction for differences in patient population in the two hospitals, the difference in the section rate was reduced to 12% vs. 8%. Whilst the major part of the higher section rate in the University Department could be explained by the greater proportion of patients with an elevated risk for Caesarean delivery, a residual difference remains. Possible explanations for this difference in the section rate between the two hospitals are discussed. PMID- 2272436 TI - [Prognosis of triplet pregnancies]. AB - 31 triplet pregnancies (DG), treated during 1975-1989, were analysed retrospectively. 13 DG (D10) were registered up to the end of the 10th week of pregnancy, 16 (DG) (D16) were intact between the 11th and the 16th gestational week. 3 DG resulted from the reduction of high grade multiple pregnancies. 18 DG (62%) of the initial 29 DG had previously been treated for sterility. The spontaneous foetal loss (DF) in group D10, including the perinatal mortality, amounted to 26% (10 of 39 DF). In one case of this group, a previously vital DF died. In another case, a partial bi-phasic abortion occurred followed by a premature birth of the surviving 3rd DF. The mortality rate in group D16, including the perinatal mortality (4 DF), was 25% (12 of 48 DF). 30 DG were still intact after the 16th week of pregnancy. 2 DG (7%) suffered from EPH-gestosis. In 4 DG (13%) a foeto-foetal transfusion syndrome occurred. 5 DF (6%) had some of the serious malformations. 27 DG were completed. 7 DG (26%) ended before the 32nd gestational week. In 13 DG (48%), a Caesarean section was performed. The perinatal mortality amounted to 11% (9 of the 81 DF) including all the births from the 25th gestational week upwards. On comparing these results with the data in the literature, a significant improvement in the prognosis of DG in recent years can be observed. This is due to the progress in antenatal and neonatal care. PMID- 2272439 TI - [Repair of vesico-vaginal fistulas using the Chassar Moir method]. AB - Besides the relatively frequent perioperative and postoperative dysfunctions of micturition, urogenital fistulae are the most frequent complication occurring after surgical gynaecologic interventions. Vesico-vaginal fistulae are the most common communication between efferent urinary passages and genital tract. From 1969 to 1986, 36 women developed a vesico-vaginal fistula after abdominal or vaginal surgery and were operated on again. Upon admission, all 36 patients were subject to surgical closure of the vesico-vaginal fistula according to the vaginal method of Chassar Moir. In 35 women (97.2%) continence was re-established by adequate closure. PMID- 2272438 TI - [Transvaginal contrast hysterosalpingo-sonography with the B-image procedure and color-coded duplex sonography for the assessment of fallopian tube patency]. AB - Transvaginal hysterosalpingo-contrast-sonography (HYCOSY), a new method for the direct assessment of tubal patency by means of ultrasonography, was employed in 68 women with infertility problems. In 67 cases, the findings were compared with hysterosal-pinography or chromolaparoscopy, performed either subsequently while the patient was still under the anaesthetic or later. The contrast demonstration of the Fallopian tubes was performed with the B mode procedure in 54 cases (Group 1) and by means of colour-coded duplex sonography in 14 (Group 2). In Group 1, the findings agreed completely in 39 cases, partially in 14 and not at all in one. In Group 2, in which 13 of the 14 cases were compared, the findings were identical in 9 cases and partially in 4. From the point of view of image documentation, the more vivid demonstration of free tubal passage in colour Doppler sonography compared to the simple B mode appears to be an advantage. Further studies are needed to determine whether contrast-perfused but dislocated tubes can be detected more easily and quickly with colour Doppler than in B mode. PMID- 2272440 TI - [Documentation of the surgical report with graphic statistical data analysis--a simplification of daily routine work]. AB - A data collection system on microcomputer connected with an automatic medical report system for operations, was developed to facilitate both medical report as well as documentation. Linking different commercial software products by use of a Pascal programme, we were able to speed up daily routine work as well as establish efficient graphical statistics of patient data. PMID- 2272441 TI - [Open uterine rupture of the pregnant uterus bicornis--a case report]. AB - A report is made on a pregnancy of a 33-year old II-gravida/I-para patient, terminating with the rupture of the uterus bicornis unicollis in the 18th week of pregnancy. The cause of this rupture was believed to be pathological disturbance of the attachment of the placenta. The early detection of uterine anomalies with ultrasonic investigation, reviewing the literature, is discussed. PMID- 2272442 TI - [Preventive appendectomy in gynecologic interventions]. PMID- 2272443 TI - [Preventive appendectomy in gynecologic interventions]. PMID- 2272444 TI - [Risks of prostaglandin treatment of tubal pregnancy]. PMID- 2272445 TI - [Histiocytosis X--histiocytosis from Langerhans' cells]. AB - A review of literature has been presented involving clinicomorphological characteristics of certain variants of histiocytosis X (HX) and current conception considering this disease as an immunopathologic process that is underlain by reactive proliferation of a specific subtype of antigen-presenting macrophages--Langerhans' cells. Clinico-morphological picture has been described and the results of successful treatment with roferon (human gene-engineering alpha 2-interferon) in 3 adult patients with HX have been presented. It is stressed that the actual effectiveness of the treatment with roferon could not be critically evaluated due to a high frequency of spontaneous remissions of this disease. PMID- 2272446 TI - [Changes in the functional properties of NK-cells and the cytostatic activity of granulocytes in acute leukemia patients]. AB - Effector activity of natural killers (NK) was studied, and functional state of NK and granulocytes was evaluated in 23 normal subjects and 28 acute leukemia patients (12 of them being in clinico-hematological remission up to 2 years). In acute leukemia significant disorders are observed in the system of nonspecific antitumor defence that is evidenced by a drastic decrease of NK activity due to changes in the functional properties of NK--their capacity for producing conjugates and blast cell lysis, low sensitivity to exogenous interferon, and lowered spontaneous cytostatic of granulocytes. PMID- 2272447 TI - [Nonspecific factors for defense of the body against infection in paraproteinemic hemoblastosis]. AB - The nonspecific defense from heterogeneous agents was sharply suppressed in patients with multiple myeloma. It was, probably, connected with the tumor growth, as well as with the influence on the factors studied of varying circumstances attending the tumor growth, such as renal insufficiency, granulocytopenia, thrombocytopenia, circulation of high-molecular pathologic protein in the blood bed, etc. No principal differences have been detected between the character of immunological disorders in multiple myeloma and Waldenstrom's macroglobulinemia. We can speak of only the degree of these disorders that, evidently, correlates with the aggressiveness of the process. PMID- 2272448 TI - [Mathematical approach to the evaluation of prognostic factors in chronic myeloid leukemia]. AB - The incidence rate of each out of 25 clinico-laboratory signs was analyzed mathematically in 87 patients with chronic myeloid leukemia, the estimation of the signs was conducted in relation to the aggressiveness of the leukemic process. Prognostically unfavourable signs have been revealed, on their basis groups of "risk" could be formed among the patients who need individually selected chemotherapy. The combination of unfavourable factors produces a noticeable effect on the mean lifetime and the disease prognosis in patients with an aggressive course of chronic myeloid leukemia. PMID- 2272449 TI - [Hematopoietins: a new agent for the treatment of hemopoietic insufficiency]. PMID- 2272450 TI - [Natural killer cells in the clinical picture of hematologic malignancies]. PMID- 2272451 TI - [Long-term regional (catheter) infusion of anticoagulants and thrombolytics in the treatment of acute and chronic arterial occlusions in patients with thromboangiitis obliterans with severe ischemia of the limbs]. AB - Catheter heparin therapy combined with the intraarterial infusion of microcrystalline suspensions of antiinflammatory and immunosuppressive agents did not provide elimination of the microcirculation block in the affected limbs of the patients with severe ischemia of the limbs. Thrombolytics used in acute and chronic thromboses in most of cases did not help in complete recanalization of the arteries. Regional thrombolysis conducted before the basic course of the arterial infusion (heparin + immunosuppressants) in patients with distal forms of the arterial affections, promoted a significant improvement of conditions of the regional microcirculation. Application of this method has permitted lowering the rate of limb amputations. PMID- 2272452 TI - [An immunoenzyme method for detection of natural antibodies to antithrombin-III in human plasma]. PMID- 2272453 TI - [Use of computers for the study of the aggregation properties of formed elements in the blood]. PMID- 2272454 TI - [Ferricyanide method of testing hemoglobin preparations]. AB - It has been shown that low concentrations of potassium chloride change almost similarly the rate constant of oxyhemoglobin autooxidation in tris-buffer and the rate constant of its oxidation by ferricyanide in the same buffer. A conclusion has been made on the principal possibility of using the latter constant as a test for oxyhemoglobin state in solution and, particularly, for its predisposition to autooxidation. PMID- 2272455 TI - [Interaction of lectins with tissue thromboplastin]. AB - Exo- and endolectins affined to N-acetylgalactosamine, N-acetylglucosamine, galactose, mannose and fucose, added in vitro to suspension of tissue thromboplastin from human brain, suppress its blood coagulation activity by 50 88% (p less than 0.05). This result has been considered as an argument for the advantage of the opinion that the specific blood coagulation centre of apoprotein III is located at the extracellular side of the cytoplasmic membrane. PMID- 2272456 TI - [Comparative analysis of thrombin and anti-thrombin antibody levels in donors and myocardial infarction patients]. AB - Thrombin and natural antithrombin antibody content was comparatively studied in donors and myocardial infarction patients. It was shown that the level of thrombin and antithrombin antibody was stable in the group of clinically normal subjects. In patients with myocardial infarction an increased thrombin level attended by a decrease in the level of natural antithrombin antibody was recorded. The presence of linear correlation between the levels of thrombin and antithrombin antibody, as well as impossibility of the diagnosis of disorders in the blood coagulation system using one of the parameters studied have permitted introduction of an additional diagnostic parameter--"antithrombin index." PMID- 2272457 TI - Pituitary control of estrogen secretion in the chick embryo: true or spurious? AB - The aim of the present study was to examine whether the hypophysis played a role in ovarian 17 beta-estradiol secretion in the chick embryo. Hypophysectomy was fulfilled by partial decapitation, which has long been codified as a practical method of hypophysectomy in the chick embryo. Ovaries from decapitated, sham operated, and intact embryos 9-19 days old were cultured in vitro during a 4-hr period, and 17 beta-estradiol released was determined by radioimmunoassay. A difference in estradiol secretion rate between decapitated and control embryos was noticed at 10-13 days, on both a per ovary and a per gram basis. At 15-19 days, there was no difference. These results suggest that the hypophysis influences the estrogen secretion of the chick embryo ovary during a limited space of time. PMID- 2272458 TI - Presence of prolactin receptors in kidney and large intestine of the snake Ptyas mucosa. AB - 125I-labeled ovine prolactin was used to test for the presence of prolactin receptors in membranes prepared from tissues of the common rat snake Ptyas mucosa. High levels of specific binding were found in kidney and large intestine membranes prepared from snakes of both sexes. The binding was time, temperature, and protein dependent. The presence of Ca2+ in the incubation medium enhanced the binding, with optimal concentrations at 10-20 mM. Specificity of binding was established by employing different hormones as the displacing species in the radioreceptor assay. The results suggested the presence of lactogenic receptors in snake kidney and large intestine membranes. Scatchard analysis of the binding data indicated the presence of a single class of binding sites in snake kidney membranes with a dissociation constant of 0.83 nM. The present study is the first report of the presence of prolactin receptors in snake kidney and large intestine membranes. PMID- 2272459 TI - The development of monoclonal antibodies against salmon (Oncorhynchus kisutch and O. keta) pituitary hormones and their immunohistochemical identification. AB - Monoclonal antibodies (MCAs) directed against several salmon pituitary hormones were generated by the fusion of myeloma cells with spleen cells from mice that had been immunized with either chum salmon (Oncorhynchus keta) growth hormone (GH) or prolactin (PRL), or one of two purified protein preparations from coho salmon (O. kisutch) pituitaries. Hybridoma were cloned by limiting dilution and screened for MCA production using immunohistochemical procedures. MCAs were generated that bound specifically to GH, PRL, or gonadotropic cells. MCAs were generated that bound to either fine granular material or large globular inclusions in the cytoplasm of the "classical" strongly PAS-positive globular gonadotropic cell type found in mature fish. This suggests that these MCAs are directed against gonadotropin II (GTH II). A MCA was also generated that bound both granular and globular material in the globular gonadotrops and granular material in the weakly PAS-positive vesicular gonadotrops in pituitaries from mature fish and to a cell type in immature rainbow trout pituitaries which is tentatively identified as the gonadotropin I (GTH I) cell type. This MCA did not bind to thyrotrops in immature rainbow trout pituitaries. PMID- 2272460 TI - Corticosterone, foraging behavior, and metabolism in dark-eyed juncos, Junco hyemalis. AB - Male, dark-eyed juncos, Junco hyemalis, were held in captivity under conditions simulating winter temperature and photoperiod. Birds were administered corticosterone (B), metapyrone (MET), or control (empty) implants in silastic tubing. B implants resulted in higher plasma levels of B, especially on the first day following implantation. After 4 days, B-implanted birds had significant atrophy of the flight muscles and increased storage of fat in the furcular and abdominal adipose depots. Despite the increased fat deposition, no differences in adipose tissue lipoprotein lipase (LPL) activity or plasma levels of glycerol or free fatty acid were observed after 4 days of treatment. There were no differences in muscle LPL activity when enzyme activity was expressed per tissue. However, when enzyme activity was expressed per gram of tissue, muscle LPL was significantly greater in the B-treated birds. Therefore, despite the atrophy of muscle tissue, the LPL enzyme had been preserved. No differences were observed in either foraging behavior or food consumption, even in light of the dramatic changes in fat and muscle masses in B-treated birds. These data are discussed in light of the chronic effects of B which may be applicable to the advanced stage of stress in birds. PMID- 2272461 TI - In vitro metabolism of progesterone, 17-hydroxyprogesterone, and 17,20 beta dihydroxy-4-pregnen-3-one by ovaries of the common carp Cyprinus carpio: production rates of polar metabolites. AB - [14C]Progesterone, 17-[3H]hydroxyprogesterone, and 17,20 beta-[3H]dihydroxy-4 pregnen-3-one (17,20 beta P) were incubated for 1, 3, 6 or 24 hr with ovaries from carp which had received injections of either carp pituitary extract or saline. All three substrates were very rapidly metabolized to polar products, but 17,20 beta P was not detected as a metabolite of either progesterone or 17 hydroxyprogesterone. The major metabolite in all incubations was very similar, but not identical, in chemical and chromatographic properties to 5 beta-pregnane 3 alpha, 6 alpha, 17,20 beta-tetrol. A compound isopolar with 5 beta-pregnane-3 alpha, 6 alpha, 17,20 alpha-tetrol was isolated only in incubations of progesterone and 17-hydroxyprogesterone. It is suggested that hydroxylation and reduction may be a deactivation mechanism allowing 17,20 beta P to build up as an intermediate, and active maturation inducing steroid, only in response to the ovulatory gonadotrophin surge, thus assisting in synchrony of oocyte maturation. PMID- 2272462 TI - Immunocytochemical localization in the central nervous system of four different insect species of molecules immunoreactive against peptides present in the caudodorsal cells of Lymnaea stagnalis. AB - The use of polyclonal antisera directed against three peptides (ovulation hormone (CDCH), alpha, and beta caudodorsal cell peptide (alpha- and beta-CDCP) produced by the caudodorsal cells of the snail Lymnaea stagnalis resulted in positive immunoreaction in Sarcophaga bullata (Diptera), Leptinotarsa decemlineata (Coleoptera), Locusta migratoria, and Periplaneta americana (Orthoptera). In three species, colocalization was detected using the antisera against CDCH and alpha-CDCP. PMID- 2272463 TI - Relaxin-like peptide in ascidians. I. Identification of the peptide and its mRNA in ovary of Herdmania momus. AB - The ovaries of the ascidian Herdmania momus were extracted for relaxin. Relaxin immunoactivity was eluted from Sephadex G-50 in the position of authentic porcine ovarian relaxin and these fractions were parallel to porcine relaxin in an homologous porcine relaxin radioimmunoassay. Poly(A)+ RNA from ascidian ovaries hybridized to a 32P-labeled porcine relaxin B-chain 48 mer oligonucleotide probe. There was no hybridization with 32P-labeled probes of equal length but was rather directed to the B-chain of human relaxin or to two different regions of the C peptide of porcine relaxin. We conclude that the ascidian ovary produces a relaxin-like molecule, possibly with greater homology in the B-chain to mammalian relaxins than in the C-peptide region. PMID- 2272464 TI - Relaxin-like peptide in ascidians. II. Bioassay and immunolocalization with anti porcine relaxin in three species. AB - A substance related to vertebrate relaxin, previously identified by radioimmunoassay and Northern hybridization in the ascidian Herdmania momus, was also purified and tested in bioassay in another species, Ciona intestinalis. In addition, immunocytochemistry with anti-porcine relaxin was performed, at the light and electron microscopic levels, on sections of ovary from three different species, living in various environmental conditions. A positive immunoreaction was located specifically in follicle cells surrounding mature oocytes. The role of this relaxin-like substance in ascidian reproduction is unknown. PMID- 2272465 TI - Immunocytochemistry of gonadotropic cells in the pituitary of Pomadasys jubelini (teleost fish). AB - An antibody specific for the beta subunit of carp gonadotropin was applied to pituitary sections from Pomadasys jubelini in order to characterize and localize the gonadotropic cells by immunocytological means. It reveals the gonadotropic zone lying mainly at the periphery of the proximal pars distalis with lateral extensions around the pars intermedia. The separation between the pars proximalis and the pars intermedia is irregular. Short finger-like extensions of the gonadotropic zone protrude more or less into the pars intermedia. The immunocytological results corroborate previous tentative identifications of the gonadotropic cells by classical cytological methods and suggest that the gonadotropic hormone produced is immunologically related with several previously studied fish gonadotropins. PMID- 2272466 TI - Measurement of developmental changes in plasma insulin-like growth factor-I levels of broiler chickens by radioreceptor assay and radioimmunoassay. AB - The main purpose of this study was to examine the relationship between insulin like growth factor-I (IGF-I) and growth hormone (GH) during embryonic and posthatching development of broiler chickens. Two heterologous assays were validated for measurement of IGF-I in chicken and turkey plasma. A radioreceptor assay (RRA), utilizing microsomal membranes prepared from human placenta, was modified and validated for measurement of IGF peptide (mainly IGF-I). A double antibody radioimmunoassay (RIA) was validated for measurement of immunoreactive IGF-I levels in chicken and turkey plasma. In both assay systems, recombinant derived human IGF-I was used for standards and trace hormone. Hypophysectomy in turkey poults reduced plasma levels of IGF (RRA) by 35% and IGF-I (RIA) by 59% as compared to intact control turkeys. In Experiment 1, 14 chicken embryos were bled at 15, 17, 19, and 21 days of incubation and at 1 week of age to determine plasma levels of IGF-I and GH. Plasma IGF levels (RRA) remained constant during late incubation, but increased significantly (P less than 0.05) at 1 week of age. Plasma IGF-I levels (RIA) declined 2 days before hatching; however, plasma levels of IGF-I were sharply elevated (P less than 0.05) at 1 week of age. Plasma GH concentrations were low in embryos and were greatly elevated (P less than 0.05) at hatching (21 days of incubation) and at 1 week of age. In Experiment 2, 12 different broiler cockerels were weighed and then bled by cardiac puncture each week from hatching (1 day of age) to 7 weeks of age. The plasma profiles of IGF, IGF-I, GH, triiodothyronine (T3), and thyroxine (T4) were each compared to relative growth rate by analysis of covariance. Plasma IGF and IGF-I levels increased progressively from 0 to 3 weeks of age and were maintained in a plateau from 3 to 7 weeks of age. Plasma GH levels reached a peak at 4 weeks of age, but declined sharply thereafter, while IGF and IGF-I levels remained elevated. Plasma T3 concentrations were progressively increased and reached peak concentrations at 3 weeks of age, while plasma T4 levels increased only at 6 and 7 weeks of age. There was a high correlation (P less than 0.01) between relative growth rate and age-related changes in plasma levels of IGF (r = 0.96), IGF-I (r = 0.97), and T3 (r = 0.94); however, there was no correlation between relative growth rate and changes in plasma GH or T4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2272467 TI - Chicken insulin-like growth factor-I: amino acid sequence, radioimmunoassay, and plasma levels between strains and during growth. AB - Insulin-like growth factor-I (IGF-I) has been purified from chicken serum and sequenced. The peptide has eight amino acid substitutions when compared with human IGF-I: serine26, leucine38, histidine39, histidine40, lysine41, glutamine50, isoleucine64, and proline67. Chicken IGF-I (cIGF-I) has been measured using a radioimmunoassay with a human IGF-I (hIGF-I) standard and an antibody raised against hIGF-I. In this assay the cross-reactivity of cIGF-I was approximately 50% with respect to hIGF-I and the cross-reactivity of chicken IGF II was 1.7% with respect to chicken IGF-I. To determine whether binding proteins in chicken plasma can artifactually interfere with IGF-I measurements as they do in mammals, chicken plasma was fractionated by molecular sieve chromatography at acid pH. When the fractions corresponding to the binding protein region were included in the IGF-I radioimmunoassay, essentially no apparent IGF-I was detected, indicating that the binding proteins did not interfere. This result, together with the finding that IGF-I in acid-ethanol extracts of chicken plasma produced parallel dose-response curves to pure cIGF-I and hIGF-I, allows the reliable measurement of cIGF-I in such extracts. The concentrations of IGF-I in plasma from male birds increased two- to threefold between 1 and 7 weeks after hatching to achieve 30-45 ng/ml. Smaller increases were found in female chickens from a higher value at 1 week. No diurnal pattern of IGF-I levels could be detected. In 4-week-old birds, the plasma concentration of the peptide fell from nearly 40 to 15 ng/ml after 24 hr of starvation and to 9 ng/ml 20 hr later. These effects are very similar to those described for mammals and strongly suggest that the regulation of IGF-I is conserved during evolution, notwithstanding the lower plasma concentrations of the growth factor in chickens. PMID- 2272468 TI - Failure to relate thyroid hormones and in vitro 5'-monodeiodination activity to oocyte development and sex steroids in the giant swamp frog Dicroglossus occipitalis at the equator. AB - Females of the giant swamp frog Dicroglossus occipitalis were captured in Zaire close to the equator in the course of 1 month. During this period, females with fully developed eggs were found, together with females of which the eggs were still in the first developmental stages. A close relationship was established between the maturation of the eggs and the studied gonadal factors: the gonadosomatic index, the oviduct weight, plasma estradiol-17 beta (E2) concentrations, plasma testosterone concentrations, and the total ovarian E2 concentrations. At the level of the thyroidal axis, the studied factors (plasma thyroxine (T4), plasma triiodothyronine (T3), plasma T3/T4 ratio, T4 and T3 concentrations, and the T3/T4 ratio in the thyroids and the 5'-monodeiodination activity (5'-D-activity) in the skin and kidney homogenates) did not show parallel changes with the maturation process of the eggs. These results indicate that no causal relation has to exist between the annual variation in thyroid hormones and the annual reproductive patterns as found in frogs from the tropical or temperate climatic region. PMID- 2272469 TI - Nuclear estrogen binding sites in the liver of the newt Pleurodeles waltl. AB - Previous investigations of the liver estrogen-specific binding in the newt, Pleurodeles waltl, have identified in the cytosol fraction, only from normal males, a new middle-affinity estrogen-binding component (MEBC) displaying the properties of type II sites reported in various tissues of vertebrates. The present work demonstrates that MEBC sites are not unique to the male but are also present in the nuclei of female animals. However, comparative study between males and females of liver nuclear sites under various extraction conditions shows sex linked differences in the subnuclear localization. The relationships between the association states of MEBC in the nuclear compartment according to sex and their presence or absence in the cytosol fraction are discussed. PMID- 2272470 TI - Cultured pituitary cell GtH response to GnRH at different stages of rainbow trout oogenesis and influence of steroid hormones. AB - In rainbow trout, a variable in vivo pituitary sensitivity to GnRH has been previously observed, depending on the stage of oogenesis. The purpose of the present work was to study, in vitro, the role of oestradiol (E2) and 17 alpha hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta P), respectively, involved in vitellogenesis and in oocyte maturation, upon this variability. The study was performed using primary cultures of whole pituitary cells from animals at different stages of oogenesis and subjected to increasing doses of salmon GnRH (sGnRH) after a 3-day pretreatment with control medium or medium supplemented with the steroid at levels corresponding to those circulating at the time of particular events of the sexual cycle (maturation and vitellogenesis). In control cultures, pituitary GtH responsiveness to sGnRH was maximal at ovulation, since at this time the gonadotrophs were able to respond to 10(-9) M sGnRH, whereas during vitellogenesis and preovulatory stages, the minimal effective dose of sGnRH ranged between 10(-6) and -8 M. We have demonstrated that 17 alpha 20 beta P has a positive or negative effect by acting directly on pituitary cell responsiveness to sGnRH, depending on the stages at which it is applied; its effect is positive during early vitellogenic and preovulatory stages whereas it is negative at the time of ovulation. E2 also increased pituitary responsiveness to sGnRH when applied during early vitellogenesis at low doses, corresponding to circulating levels at the time of ovulation; higher levels of E2, corresponding to circulating levels found during the last stages of vitellogenesis, did not modify pituitary responsiveness but increased cell GtH content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272471 TI - Cultured pituitary cell GtH response to GnRH at different stages of rainbow trout spermatogenesis and influence of steroid hormones. AB - Using primary cultures of whole dispersed pituitary cells collected from rainbow trout at different stages of spermatogenesis, basal and GnRH-induced GtH release and cell GtH content were studied in control and steroid-pretreated cultures. Steroid pretreatments were performed for 3 days with 11-ketotestosterone (11KT) and 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha 20 beta p) at levels corresponding to those circulating at the time of spermiation (50 and 20 ng/ml, respectively). In control cultures, basal GtH release and cell GtH content increased with the stage of spermatogenesis in a characteristic pattern as predicted from in vivo results concerning plasma and pituitary GtH contents. The pituitary response to salmon GnRH (sGnRH) also varied as indicated by the decrease in the minimal effective dose of GnRH able to induce a significant GtH release with the advancement of spermatogenesis: 10(-7) M at the spermatocyte stage, 10(-9) M at prespermiation and spermiation. Steroid pretreatments were shown to have a direct effect on pituitary gonadotrophs and particularly on pituitary response to sGnRH, depending on the stage at which they are applied. At the beginning of spermatogenesis both of them induced an increase in GtH release and at prespermiation they have a slight negative effect, significant only with 17 alpha 20 beta P. At spermiation they have no effect except for 17 alpha 20 beta P which increased the response to 10(-8) M of sGnRH. Results are discussed in relation to hormonel changes (gonadotropin and steroid) observed by different authors during the sexual cycle. PMID- 2272472 TI - Action of estradiol on mullerian duct regression induced by treatment with norethindrone of female chick embryos. AB - Treatment of genetically female chick embryos with norethindrone (NET), a progesterone-like steroid chemically related to testosterone, caused two types of Mullerian duct (MD) deficiencies. The first consisted in an absence of the caudal part of the ducts owing to their partial agenesia occurring between Days 5 and 7 of embryonic life. This is nonspecific since it was observed after a treatment with almost all steroidal sex hormones. In particular, this was obtained with estradiol which also increases the frequency and extent of agenesia caused by the NET, as reported here. The second type of deficiency appeared between Days 12 and 14 and was due to a regression destroying the more or less large part of the MDs having escaped agenesia, i.e., for most of the cephalic half. This resulted from the influence of the anti-Mullerian hormone originating from the ovary and normally inhibited by the ovarian estrogens. This protective action of endogenous estrogens was inhibited by the NET, but an additional treatment with estradiol removed this inhibition and prevented duct regression. Our results suggest that estrogen protects the duct from the regression induced indirectly by NET, by acting both at gonad and MD levels. PMID- 2272474 TI - Enhanced vasoactive intestinal peptide-induced prolactin secretion from anterior pituitary cells of incubating turkeys (Meleagris gallopavo). AB - During incubation, female turkeys exhibit elevated circulating prolactin (PRL) which may be the result of enhanced pituitary responsiveness to vasoactive intestinal peptide (VIP). This hypothesis was tested by comparison of spontaneous and porcine VIP-induced PRL secretion from anterior pituitary cells of hens in various reproductive conditions. The effect of VIP and luteinizing hormone releasing hormone (LHRH), alone and in combination, on luteinizing hormone (LH) secretion was also examined. Incubation with pVIP (10(-10) to 10(-6) M) significantly stimulated PRL secretion at all incubation times tested (1-5 hr). This increase was greatest in cells from incubating hens, with those from laying, photorefractory, and quiescent (nonphotostimulated) hens secreting successively less PRL. These responses were obtained when spontaneous PRL secretions were compared. VIP induced approximately a similar 1.5-fold increase in LH secretion, in all reproductive groups. Also, VIP enhanced LHRH-induced LH secretion (1.2- to 1.6-fold; P less than 0.0001). It is concluded that PRL secretion in vitro by pituitary cells from turkey hens in various reproductive stages reflects the circulating levels of PRL at these stages. PMID- 2272473 TI - Differences in salmon GnRH and chicken GnRH-II contents in discrete brain areas of male and female rainbow trout according to age and stage of maturity. AB - We have developed sensitive and specific radioimmunoassays (RIA) for salmon gonadotropin-releasing hormone (sGnRH) and chicken GnRH-II (cGnRH-II). Synthetic sGnRH and cGnRH-II(2-10) were conjugated to bovine serum albumin and injected into rabbits to raise specific antisera. The antiserum against sGnRH showed cross reactivities of 1.58 and 0.08% for cGnRH-II and lamprey GnRH, respectively. The antiserum against cGnRH-II showed cross-reactivities of 0.05 and 0.01% for sGnRH and lamprey GnRH, respectively. Both antisera were observed not to cross-react with mammalian GnRH and cGnRH-I or other peptide hormones. Synthetic sGnRH and cGnRH-II were iodinated using the chloramine-T method. The iodinated GnRH was purified by HPLC using a reverse-phase C18 column. The RIA system was developed as a double antibody method. Brain extracts of rainbow trout showed displacement curves which were parallel to the sGnRH and cGnRH-II standards in each RIA. HPLC analysis followed by RIA has revealed that rainbow trout brain contains two types of GnRH: sGnRH and cGnRH-II. Total sGnRH content in the brain was about three fold higher than that of cGnRH-II. In the olfactory bulbs, telencephalon, optic tectum-thalamus, hypothalamus, and pituitary, sGnRH content (per region) was higher than cGnRH-II content, whereas cerebellum and medulla oblongata contained much more cGnRH-II than sGnRH. sGnRH content in the optic tectum-thalamus and pituitary was the highest in 1-year-old immature fish and 3-year-old mature fish, respectively. Medulla oblongata showed the highest cGnRH-II content in all groups. sGnRH concentrations (per milligram of protein) were high in the pituitary and intermediate in the olfactory bulbs, hypothalamus, and telencephalon. In all groups, the cGnRH-II concentration was high in the medulla oblongata, whereas the concentration in the olfactory bulbs and pituitary gland was below the detectable limit in most individuals. PMID- 2272475 TI - Influence of dietary lipid and carbohydrate levels and chronic 3,5,3'-triiodo-L thyronine treatment on thyroid function in immature rainbow trout, Oncorhynchus mykiss. AB - The influence of varying dietary levels of nonprotein energy sources (lipid, L; carbohydrate, C) and 3,5,3'-triiodo-L-thyronine (T3) on thyroid function in immature rainbow trout was studied. Three diets of equivalent available energy content and identical nutrient composition, except for dissimilar concentrations of L and C (diet 1, L = 7%, C = 28.3%; diet 2, L = 13%, C = 14.9%; diet 3, L = 19%, C = 1.5%), were each supplemented with 0, 4, 8, or 12 ppm T3 and fed to satiation to trout at 6.5 +/- 0.5 degrees on a 12-hr photoperiod for 12 weeks. Dietary L and C concentrations did not influence plasma total L-thyroxine (T4) or T3 levels, indices of free T4 or free T3 levels, hepatic T4 5'-monodeiodinase (5'D) activity, capacity or affinity of hepatic nuclear T3 receptors, or thyroid follicle epithelial cell height. T3 treatment elevated total and free T3 levels and decreased 5'D activity (Vmax) in approximate proportion to T3 dose, and without effect on plasma total or free T4 levels or T3 receptor properties. However, thyroid follicle epithelial cell height was depressed at 8 or 12 ppm dietary T3. In trout reverted for 20 days to a T3-free diet from a T3 (12 ppm) diet, plasma total T3 levels fell to 30% of those of control trout (0 ppm T3 throughout). It was concluded that, under our experimental conditions, (i) trout thyroid function was refractory to dietary concentrations of L and C, (ii) the primary response to T3 supplementation was suppressed hepatic 5'D level and T3 production, which was sustained for at least 20 days after T3 treatment ceased, and (iii) despite causing a probable indirect decrease in thyroidal secretion, T3 did not modify the set point of the hypothalamo-hypophyseal-thyroid axis based on plasma total or free T4 levels. PMID- 2272476 TI - In vitro goldfish growth hormone responses to gonadotropin-releasing hormone: possible roles of extracellular calcium and arachidonic acid metabolism? AB - Two hours of incubation of primary static cultures of dispersed goldfish pituitary cells with 0.01 nM to 1 microM [Trp7,Leu8]-gonadotropin-releasing hormone (sGnRH) increased growth hormone (GH) secretion in a dose-dependent manner with an ED50 estimate of 0.13 +/- 0.04 nM. Addition of calcium ionophores, 1 to 100 microM A23187 and 5 to 100 microM ionomycin, significantly elevated GH release with ED50s of 0.84 +/- 0.38 and 4.34 +/- 1.02 microM, respectively. Replacement of normal calcium-containing media with calcium-deficient media (prepared without the addition of calcium salts) significantly depressed basal GH secretion, attenuated the A23187- and ionomycin-stimulated GH release, and completely abolished the GH response to sGnRH. Arachidonic acid (AA) at 1 to 50 microM also enhanced GH secretion with an ED50 of 4.72 +/- 1.52 microM. Coincubation with 1 and 10 microM of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), 10 microM of the cyclooxygenase inhibitor, indomethacin, and 10 microM of eicosatetraynoic acid, an enzyme blocker with mixed activities on both the lipoxygenase and cyclooxygenase pathways, did not alter basal, AA-, and sGnRH-induced GH release. However, at 100 microM concentration, NDGA increased AA- and sGnRH-stimulated, as well as basal GH, responses. These results confirm the direct stimulatory action of GnRH on goldfish somatotropes and indicate the importance of extracellular calcium in mediating basal and GnRH-induced GH responses. Although AA stimulates GH secretion, its lipoxygenase and cyclooxygenase metabolites probably do not mediate sGnRH action on somatotropes. PMID- 2272477 TI - Response of the pigeon crop sac to mammotrophic hormones: comparison between relaxin and prolactin. AB - The effects of relaxin (RLX), a hormone that has previously been demonstrated to have mammotrophic properties, were studied in the pigeon crop sac, a well-known target organ for mammotrophic and lactogenic hormones, and compared with the effects produced by prolactin (PRL). The two hormones were injected directly over the crop at different doses and the response was evaluated after differing times of exposure. RLX causes a dose-related increase in wet and dry weights and [3H]thymidine and [3H]uridine uptake by the crop mucosa, as well as morphological changes indicating growth and differentiation of the epithelial cells similar to those occurring during physiological activation in incubation and hatching. At the doses assayed, the effects of RLX were nearly identical to those obtained following PRL in the short-term experiments, but differences in functional responses were found in the long-term experiment. PMID- 2272478 TI - The source of circulating catecholamines in forced dived ducks. AB - Plasma catecholamines have been measured in chronically adrenalectomized (ADX) ducks, in chronically adrenal-denervated ducks (DNX), and in their respective shamoperated controls (SH-adx, SH-dnx) after 3 min forced submergence. The results showed that 100% of the plasma epinephrine (EP) and 70 to 80% of plasma norepinephrine (NE) released during the dive came from the adrenal glands. Only 20 to 30% of plasma NE came from the endings of the autonomic vascular sympathetic nerves which are strongly stimulated during diving. Adrenal catecholamines were released by nerve activation only; nonneural mechanisms did not play any role in their release. The action of adrenal catecholamines on the cardiovascular system during dives was investigated by measuring heart rate and arterial blood pressure in operated and sham-operated ducks. Cardiovascular adjustments, associated with 3 min of forced diving, were not affected by any differences in the levels of plasma catecholamines. PMID- 2272479 TI - Antiestrogens fail to prevent the masculine ontogeny of the zebra finch song system. AB - Early treatment with the antiestrogen, tamoxifen, fails to block the ontogeny of the male zebra finch song system which is hypothesized to occur as a result of early estradiol action. In Experiment 1, two other antiestrogens, LY117018 or CI628, or vehicle was administered daily to zebra finch chicks for the first 20 days after hatching at which time the males were castrated. Comparisons of experimental and control brains at 60 days revealed that neither antiestrogen prevented the masculinization of the song system in males. Rather, both compounds increased (hypermasculinized) neuronal soma area in male MAN (magnocellular nucleus of the anterior neostriatum), DLRA (dorsolateral portion of the robust nucleus of the archistriatum), and in HVc (caudal nucleus of the ventral hyperstriatum). In females both compounds masculinized by increasing neuronal soma area in HVc and inducing the formation of Area X. Experiment 2 showed that neither LY117018 nor CI628 was effective in preventing the masculinization of the song system typical of 25-day-old males when administered daily from hatching until sacrifice. Rather, both compounds masculinized females by inducing the formation of Area X, and LY117018 increased RA volume. LY117018 hypermasculinized males by increasing HVc volume and size of neuronal somata in MAN, HVc, and DLRA. CI628 also hypermasculinized males by increasing RA volume and neuronal soma size in HVc and RA. The failure of the present compounds to block masculinization of the song system and the paradox of hypermasculinization by antiestrogens are discussed with reference to the estradiol-masculinization hypothesis. PMID- 2272480 TI - Molecular isoforms of chicken growth hormone (cGH): different bioactivities of cGH charge variants. AB - It has been suggested that the functional diversity of growth hormone (GH) is related to its molecular complexity. Here we report a characterization of charge and mass variants of chicken growth hormone (cGH) through a variety of electrophoretic systems [nondenaturing (ND-PAGE), denaturing (SDS-PAGE), under reducing and nonreducing conditions, isoelectrofocusing (IEF), and bidimensional electrophoresis] followed by Western blot and immunostaining with a specific antibody directed against pure cGH. We also report the biological properties of two charge variants on two homologous assays. The studies were carried out with purified cGH and with fresh chicken pituitary extracts. Three charge variants were obtained by ND-PAGE (Rf = 0.23, 0.30, and 0.35), which showed the same molecular weight (26 kDa), while in IEF eight isoforms were observed, the most conspicuous being those with pI = 6.86, 7.5, 7.9, 8.05, and 8.18. In SDS-PAGE under reducing conditions four immunoreactive bands were observed: the monomer (26 kDa), a dimer (52 kDa), a fragment (16 kDa), and a minor band at 22 kDa. Higher MW variants were found under nonreducing conditions. Bidimensional analysis also showed several charge variants for the monomer and the dimer. Bioactivity of two charge variants (0.23 and 0.3) was evaluated with a lipolytic and an antilipolytic assay on chicken adipose tissue explants. It was shown that variant 0.23 was mainly lipolytic, in a dose-dependent response, but lacked antilipolytic effect. On the other hand, variant 0.30 did not show lipolytic effect but presented a clear antilipolytic activity. PMID- 2272481 TI - Glucocorticoid-mediated activation of DNA degradation in avian lymphocytes. AB - Little information is known about the molecular mechanism of programmed cell death in the avian species. In the current study we have analyzed this process in chickens using a glucocorticoid-lymphocyte model system. Three-week-old male broiler chicks were treated in vivo with the synthetic glucocorticoid, dexamethasone. Following this treatment genomic DNA was isolated from thymocytes and analyzed by agarose gel electrophoresis. Dexamethasone activated a DNA degrading process in which the genome was specifically cleaved at internucleosomal intervals. This steroid-induced response occurred prior to thymocyte cell death and was time and glucocorticoid dose dependent, as well as tissue and steroid specific. Only the glucocorticoid class of steroid hormones could elicit this response and DNA degradation was only detectable in lymphoid tissues that contained immature lymphocytes. Internucleosomal DNA degradation could also be elicited via administration of adrenocorticotrophic hormone, a treatment that elevates endogenous glucocorticoids. Based on these data, glucocorticoid-activated DNA degradation of the avian thymocyte genome appears to be a steroid receptor-mediated process which involves the activation of an endogenous nuclease that cleaves the genome at internucleosomal sites. Degradation of the thymocyte genome occurs prior to cell death and may represent an initial event in a cascade of hormone-mediated processes that culminate in a type of cellular suicide referred to as programmed cell death. PMID- 2272482 TI - Further experimental evidence in support of the involvement of ovarian follicles in oocyte maturation of the Indian catfish, Mystus vittatus. AB - The role of the ovarian follicular layer in the oocyte maturation of the Indian catfish, Mystus vittatus, was investigated in vitro using cyanoketone and epostane (specific inhibitors of the 3 beta-hydroxysteroid dehydrogenase enzyme system). Folliculated oocytes incubated with luteinizing hormone (LH) at the concentration of 10 micrograms/ml induced 67.7 +/- 1.5% of germinal vesicle breakdown (GVBD). When the oocytes were incubated with LH + cyanoketone or epostane, there was a significant drop in the frequency of GVBD. It revealed that the maturational response of M. vittatus oocytes to LH depends on the synthesis of delta 4 steroids (probably 17 alpha,20 beta-dihydroxy-4-pregen-3-one; 17 alpha,20 beta-diOHprog) from the follicular layer since both the inhibitors failed to abolish the maturational effect of 17 alpha, 20 beta-diOHprog (the most potent maturation-inducing steroid for this species). PMID- 2272483 TI - Plasma growth hormone levels increase during seawater exposure of sexually mature Atlantic salmon parr (Salmo salar L.). AB - At the time of smoltification in May, smolts and sexually mature male parr were transferred to seawater (25% salinity) and sampled after 6 and 24 hr. Plasma levels of growth hormone (GH) were measured by radioimmunoassay. There was no difference in GH levels between smolts and mature parr in fresh water. GH levels did not change during exposure of smolts to seawater. In the mature male parr, plasma GH levels increased after 24 hr, when the levels were almost five times those of the freshwater controls. In the mature male parr, there was an increase in plasma osmolality, sodium, and magnesium after 24 hr in seawater; magnesium also increased after 6 hr. The levels of potassium and calcium did not change in either immature parr or mature male parr. The increase in plasma GH levels in the mature parr in seawater may be part of a mechanism to increase hypoosmoregulatory ability in fish not ready for seawater entry. PMID- 2272484 TI - Ecdysteroid fluctuations during embryogenesis in the giant freshwater prawn, Macrobrachium rosenbergii. AB - Ecdysteroid levels during the embryogenesis of the giant freshwater prawn, Macrobrachium rosenbergii, were determined by radioimmunoassay and high performance liquid chromatography. Ecdysteroids consisting of significant amounts of 20-hydroxyecdysone and high-polarity products (HPP) and lesser amounts of ecdysone and low-polarity products (LPP) were detected in mature ovaries and newly laid eggs. All ecdysteroid groups decreased gradually during the nauplius phase. With the formation of the compound eye and the appearance of the carapace and other body-like structures, marking morphogenesis to the zoeal stage, embryos showed the beginning of a continuous and dramatic increase in ecdysteroid concentrations sustained until larval hatchout. Ecdysteroid levels at hatchout were above 20-fold greater than ecdysteroid levels in newly laid eggs. More specifically, HPP and 20-hydroxyecdysone increased concomitantly, with a decrease in 20-hydroxyecdysone only at the end of the embryogenic period, while ecdysone and LPP levels remained low or undetectable. It may be postulated that the presence of ecdysteroids in ovaries and eggs represents a reserve of maternal ecdysteroids which are necessary at the commencement of embryonic development; with the differentiation of embryonic tissue capable of ecdysteroid synthesis, ecdysteroids increase rapidly to play a role in later embryonic development. PMID- 2272485 TI - Photoorientation, motility and pigmentation in a freshwater peridinium affected by ultraviolet radiation. AB - The effects of ultraviolet radiation on orientation, motility and pigmentation were measured in the freshwater dinoflagellate, Peridinium gatunense. Histograms of the positive phototactically oriented cells showed a decrease in the degree of orientation even after short exposure times. Quantification of the orientation revealed a significant inhibition after 2 h exposure. Similarly, the percentages of motile cells and the mean linear velocity of the cells was strongly affected. UV radiation also caused a massive bleaching of the cellular pigments as shown by absorption spectra determined after increasing exposure times. The ecological consequences of these effects are discussed. PMID- 2272486 TI - Semiconductor properties of melanins prepared from catecholamines. AB - D. C. dark - and photoconductivity measurements were performed with synthetic melanins prepared by oxidative polymerization of dopamine, adrenaline, adrenochrome and adrenolutin. The melanins examined show significant differences in conductivity, thermal activation energy and photocurrent intensity values. The differences in semiconductor properties observed between the melanins reflect the structure differences of catecholamine-melanin polymers. PMID- 2272487 TI - Serum and brain aminopeptidase activities in cyclic rats. AB - Research into the functional role of brain peptides is performed, in part, by studying peptidase enzymes which might be involved in the processing or inactivation of the brain peptides. Aminopeptidase activity has been proposed as a candidate for the regulation of the degradation of these peptides. In this paper, acid (Asp-) and basic (Arg-) aminopeptidase activities were studied in several brain regions and in the serum during the estrous cycle of the rat. Asp aminopeptidase activity did not significantly change at any point. However, a marked rise was found in Arg-aminopeptidase activity in all the brain areas studied and the serum during the proestrus. It is suggested that this activity plays a role in the hormonal changes that take place during the cycle, possibly in regulating the activity of several neuroactive peptides. PMID- 2272488 TI - Stimulation of the sodium transport across the frog skin by three N-terminally extended arginine-vasopressins. AB - The standard Ussing method was used to electrophysiologically characterize the effects of three analogs of arginine-vasopressin (AVP) on the frog skin, a model Na-transporting epithelium. The analogs tested were N-terminally extended Arg8 vasopressins: Ala-AVP, Ser-Ala-AVP and Thr-Ser-Ala-AVP; synthetic Arg8-AVP was used as the reference agent. The vasopressins were applied to the basolateral side of the frog skin in concentrations ranging between 10(-8) to 10(-5) mol.l-1. All the three analogs increased both the short-circuit current (Isc) and the open circuit transepithelial potential (Voc), and decreased the transepithelial d.c. resistance (Rt) similarly as did synthetic Arg8-AVP. The results show that N terminal extension of the Arg8-AVP did not alter the natriferic properties of AVP. PMID- 2272489 TI - Interaction of Mn(II) ions with human serum albumin. PMID- 2272490 TI - Two distinct conformers coexist in a synthetic DNA poly(dA-dT).Poly(dA-dT) in low salt aqueous solution. PMID- 2272491 TI - Increase in calcium triggers mating structure activation in Chlamydomonas eugametos. AB - For mating Chlamydomonas eugametos gametes to fuse with their partners, they must first lyse part of the anterior cell wall and protrude their mating structures. These responses can be artificially induced by compounds that raise the Cai level, viz. InsP3, A23187, TFP and ethanol. We conclude that calcium should be considered with cAMP to be involved in signal transduction during C. eugametos mating. PMID- 2272492 TI - Enterococcus columbae, a species from pigeon intestines. AB - Gram-positive cocci which dominate in the intestinal flora of domestic pigeons were found to constitute a new species of the genus Enterococcus. The strains were most closely related to Enterococcus cecorum, originally described as Streptococcus cecorum, a carboxyphilic species from chicken intestines, and to Enterococcus avium. The pigeon strains resemble E. cecorum and also many E. avium strains in their lack of group D antigen and in being more sensitive to NaCl than other enterococci. The type strain is strain STR 345 (= NCIMB 13013). PMID- 2272493 TI - Solubilisation of a cell wall bound invertase in Aspergillus nidulans. AB - Aspergillus nidulans produces an extracellular invertase when incubated in the presence of sucrose and about half of the activity produced was found to be associated with the mycelium. Sixty percent of this mycelial invertase could be solubilised by simple mechanical disruption. Among the agents tested for solubilisation of invertase, proteinase K and dithiothreitol were the most effective. PMID- 2272494 TI - pS10147-2, a 3.7 kb multicopy plasmid isolated from Streptomyces coelicolor. AB - The multicopy plasmid, pS10147-2 (3.7 kb) was isolated from Streptomyces coelicolor IMET 40271. A restriction enzyme map of pS10147-2 was constructed. The pS10147-2 is probably a spontaneous deletion derivative of pIJ101. PMID- 2272495 TI - Cloning and sequencing of the gene coding for the elongation factor 1 alpha from the archaebacterium Thermoplasma acidophilum. AB - The gene which encodes the elongation factor 1 alpha (EF-1 alpha) of the archaebacterium Thermoplasma acidophilum (tuf-gene) has been cloned and sequenced. The gene coding for elongation factor EF-2 was found downstream from the 3' end of the tuf-gene. Comparison of the predicted amino acid sequence of Thermoplasma EF-1 alpha with EF-1 alpha sequences of other organisms showed that the highest similarity values were found between T. acidophilum and Methanococcus vannielii. PMID- 2272496 TI - Association of a 38 kDa bovine serum protein with the outer membrane of Bordetella pertussis. AB - Upon cultivation of Bordetella pertussis in bovine serum, a 38 kDa protein was found to be tightly associated with the outer membrane. The intensity of the 40 kDa porin was reduced under these growth conditions. Exposure of Bordetella pertussis, grown in Stainer and Scholte medium, to bovine serum for 1 h did not result in the appearance of the 38 kDa protein. Unlike the 40 kDa porin however, the electrophoretic mobility of this protein was affected neither by temperature of denaturation nor by the presence of 2-mercaptoethanol. Amino acid sequence analysis of the N-terminal of the 38 kDa protein revealed that his protein had 87% homology to both the mouse and human complement C3 precursors. PMID- 2272497 TI - Direct selection of monoclonal antibodies neutralising the cytotoxic activity of Aeromonas sobria. AB - Monoclonal antibodies directed against the cytotoxic activity of Aeromonas sobria were raised by immunising mice with a culture supernatant concentrated by ammonium sulphate precipitation. Neutralising antibodies were specifically selected for by exposing hybridomas to cytotoxic levels of the immunising preparation. Cultures free from cytopathic effects after three hours were selected for further investigation. Ten cytotoxin resistant hybridomas were isolated but only two of these produced detectable neutralising activity in Vero and rabbit red blood cell assays. Different polypeptide binding patterns were observed for the neutralising antibodies compared with the other antibodies in immunoblotting studies. One of the neutralising antibodies was shown to act at an early stage in the development of cytotoxicity, probably by inhibiting binding. PMID- 2272498 TI - Nucleotide sequence of the thermostable direct hemolysin gene (tdh gene) of Vibrio mimicus and its evolutionary relationship with the tdh genes of Vibrio parahaemolyticus. AB - The gene encoding a hemolysin similar to the thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus was previously cloned from the chromosome of Vibrio mimicus. The nucleotide sequence of the hemolysin gene was determined in this study. The gene proved to be a variant of the thermostable direct hemolysin gene (tdh gene) and was designated as Vm-tdh because the sequence divergences between the Vm-tdh gene and four tdh genes of V. parahaemolyticus were 2.1-3.0%, while the sequence divergences among the four tdh genes of V. parahaemolyticus ranged between 1.4 and 3.3%. Analysis of these five tdh genes revealed that they evolved from a common ancestor in discrete and understandable order by sporadic base substitutions. PMID- 2272499 TI - The pattern of X-chromosome inactivation in the embryonic and extra-embryonic tissues of post-implantation digynic triploid LT/Sv strain mouse embryos. AB - Spontaneously cycling LT/Sv strain female mice were mated to hemizygous Rb(X.2)2Ad males in order to facilitate the distinction of the paternal X chromosome, and the pregnant females were autopsied at about midday on the tenth day of gestation. Out of a total of 222 analysable embryos recovered, 165 (74.3%) were diploid and 57 (25.7%) were triploid. Of the triploids, 26 had an XXY and 31 an XXX sex chromosome constitution. Both embryonic and extra-embryonic tissue samples from the triploids were analysed cytogenetically by G-banding and by the Kanda technique to investigate their X-inactivation pattern. The yolk sac samples were separated enzymatically into their endodermally-derived and mesodermally derived components, and these were similarly analysed, as were similar samples from a selection of control XmXp diploid embryos. In the case of the XmXmY digynic triploid embryos, a single darkly-staining Xm chromosome was observed in 485 (82.9%) out of 585, 304 (73.3%) out of 415, and 165 (44.7%) out of 369 metaphases from the embryonic, yolk sac mesodermally-derived and yolk sac endodermally-derived tissues, respectively. The absence of a darkly staining X chromosome in the other metaphase spreads could either indicate that both X chromosomes present were active, or that the Kanda technique had failed to differentially stain the inactive X-chromosome(s) present. In the case of the XmXmXp digynic triploid embryos, virtually all of the tissues analysed comprised two distinct cell lineages, namely those with two darkly-staining X-chromosomes, and those with a single darkly staining X-chromosome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272500 TI - Grammatical analysis of DNA sequences provides a rationale for the regulatory control of an entire chromosome. AB - Regardless of their origins, functions, and base compositions, all DNAs are scriptures written following the same grammatical rule. At the level of syllables, two, CG and TA are seldom used, while three, TG, CT and CA are utilized with abundance. Accordingly, at the level of three-letter words, two complementary base trimers, CTG and CAG, invariably enjoy frequent usage. Inasmuch as two of the three frequently used syllables, TG and CA are complementary to each other, while two seldom used syllables, CG and TA, are both palindromes, two complementary strands of DNA are inherently symmetrical with each other. Consequently, palindromic sequences as favourite targets of DNA binding proteins occur at unsuspectedly high frequencies, if they contain TG and CA or CTG and CAG. Nevertheless, there are grammatical rules operating among these high frequency palindromes as well; e.g. the palindromic tetramer TGCA occurs nearly two times more often than its reciprocal; CATG. Thus, DNA-binding proteins are provided with a wealth of abundant targets whose densities are influenced by a regional difference in GC/AT ratios to variable degrees. One palindromic heptamer CAGNCTG is an ideal target of one DNA-binding protein engaged in chromosome packaging and in generation of banding patterns. This heptamer occurs once every 1000 bases in moderately GC-rich sequences, while its incidence is reduced to once every 3000 bases in extremely AT-rich sequences. The above must be the very reason that a solitary human X-chromosome DNA coated with mouse DNA-binding proteins in mouse-man somatic hybrids still maintains the original banding pattern and that the inactive X remains inactive, while the active X remains active. PMID- 2272501 TI - Illegitimate pairing of the X and Y chromosomes in Sxr mice. AB - X/Y male mice carrying the sex reversal factor, Sxr, on their Y chromosomes typically produce 4 classes of progeny (recombinant X/X Sxr male male and X/Y non Sxr male male, and non-recombinant X/X female female and X/Y Sxr male male) in equal frequencies, these deriving from obligatory crossing over between the chromatids of the X and Y during meiosis. Here we show that X/Y males that, exceptionally, carry Sxr on their X chromosome, rather than their Y, produce fewer recombinants than expected. Cytological studies confirmed that X-Y univalence is frequent (58%) at diakinesis as in X/Y Sxr males, but among those cells with X-Y bivalents only 38% showed normal X-Y pseudo-autosomal pairing. The majority of such cells (62%) instead showed an illegitimate pairing between the short arms of the Y and the Sxr region located at the distal end of the X, and this can be understood in terms of the known homology between the testis determining region of the Y short arm and that of the Sxr region. This pairing was sufficiently tenacious to suggest that crossing over took place between the 2 regions, and misalignment and unequal exchange were suggested by indications of bivalent asymmetry. Metaphase II cells deriving from meiosis I divisions in which the normal X-Y exchange had not occurred were also found. The cytological data are therefore consistent with the breeding results and suggest that normal pseudo autosomal pairing and crossing over is not a prerequisite for functional germ cell formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272502 TI - Sex chromosome configurations in pachytene spermatocytes of an XYY mouse. AB - Karyotypic investigation of a phenotypically normal but sterile male mouse showed the presence of an XYY sex chromosome constitution. The synaptic behaviour of the three sex chromosomes was examined in 65 pachytene cells. The sex chromosomes formed a variety of synaptic configurations: an XYY trivalent (40%); an XY bivalent and Y univalent (38.5%); an X univalent and YY bivalent (13.8%); or X, Y, Y univalence (7.7%). There was considerable variation in the extent of synapsis and some of the associations clearly involved nonhomologous pairing. These observations have been compared with previously published information on chromosome configurations at metaphase I from other XYY males. PMID- 2272503 TI - The parental origin of de novo X-autosome translocations in females with Duchenne muscular dystrophy revealed by M27 beta methylation analysis. AB - The parental origin of 3 de novo X-autosome translocations in females with Duchenne Muscular Dystrophy (DMD) was studied by means of methylation analysis using the X-linked probe M27 beta. In all three the translocation was found to be paternal in origin. The parental origin of X-autosome translocations in females with and without DMD is compared with other structural abnormalities of the X and with autosomal translocations. PMID- 2272504 TI - Localization of the properdin factor complement locus Pfc to band A3 on the mouse X chromosome. AB - The locus for properdin (properdin factor complement, Pfc), a plasma glycoprotein, has been mapped to band A3 of the mouse X chromosome by in situ hybridization to metaphase spreads containing an X;2 Robertsonian translocation. The X-linkage of the locus has also been confirmed by analysis of Mus musculus x Mus spretus interspecific crosses. The XA3 localization for Pfc places it in the chromosomal segment conserved between man and mouse which is known to contain at least six other homologous loci (Cybb, Otc, Syn-1 Maoa, Araf, Timp). PMID- 2272505 TI - Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus. AB - Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies. PMID- 2272506 TI - Hst-3: an X-linked hybrid sterility gene. AB - A gene, Hst-3, responsible for sterility in F1 males from crosses between Mus spretus and laboratory strains of mice such as C57BL/6, has been localized on the distal part of the X chromosome, using both DNA probes and biochemical markers on a panel of F1(C57BL/6 x SEG) x C57BL/6 backcross males. This gene may be a model for studying mammalian hybrid sterility. PMID- 2272507 TI - The hairy ears (Eh) mutation is closely associated with a chromosomal rearrangement in mouse chromosome 15. AB - The mouse mutation hairy ears (Eh) originated in a neutron irradiation experiment at Oak Ridge National Laboratory. Subsequent linkage studies with Eh and other loci on Chr 15 suggested that it is associated with a chromosomal rearrangement that inhibits recombination since it shows tight linkage with several loci occupying the region extending from congenital goiter (cog) distal to caracul (Ca). We report here (1) linkage experiments confirming this effect on recombination and (2) meiotic and mitotic cytological studies that confirm the presence of a chromosomal rearrangement. The data are consistent with the hypothesis of a paracentric inversion in the distal half of Chr 15. The effect of the inversion extends over a minimum of 30 cM, taking into account the genetic data and the cytologically determined chromosomal involvement extending to the region of the telomere. PMID- 2272508 TI - Deletion analysis of male sterility effects of t-haplotypes in the mouse. AB - We present data on the effects of three chromosome 17 deletions on transmission ratio distortion (TRD) and sterility of several t-haplotypes. All three deletions have similar effects on male TRD: that is, Tdel/tcomplete genotypes all transmit their t-haplotype in very high proportion. However, each deletion has different effects on sterility of heterozygous males, with TOr/t being fertile, Thp/t less fertile, and TOrl/t still less fertile. These data suggest that wild-type genes on chromosomes homologous to t-haplotypes can be important regulators of both TRD and fertility in males, and that the wild-type genes concerned with TRD and fertility are at least to some extent different. The data also provide a rough map of the positions of these genes. PMID- 2272509 TI - Inheritance of T-associated sex reversal in mice. AB - We previously identified a primary sex-determining locus, Tas, on mouse Chr 17 that causes ovarian tissue development in C57BL/6J Thp/+ and TOrl/+ individuals if the AKR/JY chromosome is present. We hypothesized that Tas is located within the region of Chr 17 deleted by Thp and TOrl and that C57BL/6J carries a diagnostic Tas allele, based on the observation that ovarian tissue develops in XY mice when Thp is on a C57BL/6J inbred strain background, whereas normal testicular development occurs when Thp is on a C3H/HeSnJ inbred strain background. To test this hypothesis, we mated (C57BL/6J x C3H/HeSnJ)F1 females to C57BL/6J Thp/+ hermaphrodites. As expected, half of the XY Thp/+ offspring developed ovarian and testicular tissue while half developed exclusively testicular tissue. Unexpectedly, the inheritance of selected Chr 17 molecular loci was independent of gonadal development, as half of the male and hermaphroditic offspring inherited C3H/HeSnJ-derived Chr 17 loci and half inherited C57BL/6J-derived Chr 17 loci. We conclude that for ovarian tissue to develop in an XY Thp/+ or XY TOrl/+ individual (1) Tas must be present in a hemizygous state, which is accomplished by heterozygosity for the Thp or TOrl deletions; (2) the AKR/J-derived Y chromosome must be present; and (3) an additional locus involved in primary sex determination must be present in a homozygous C57BL/6J state. This newly identified gene may be one of the previously defined loci, tda-1 or tda-2. PMID- 2272510 TI - Expression of three t-complex genes, Tcp-1, D17Leh117c3, and D17Leh66, in purified murine spermatogenic cell populations. AB - Transmission ratio distortion (TRD) is a property of the complete t-haplotype which results in the preferential transmission of the t-haplotype chromosome from heterozygous t/+ males to the majority of the progeny. Available data suggest that in t/+ males, a dysfunction of the wild-type sperm within the female reproductive tract is responsible for the observed deviation from Mendelian segregation ratios. Genetically, Lyon has shown that multiple loci within the t complex are required for maximum levels of TRD. These loci include multiple t complex distorters (Tcds) which act upon a single t-complex responder (Tcr). Testis-expressed genes have been cloned which map to the same subregions of the t complex as the Tcds and Tcr and are thus considered candidate genes for the products of these loci. To begin to understand how the products of these loci biochemically control TRD, the expression of three TRD-candidate genes (Tcp-1, D17Leh117c3, and D17Leh66) has been determined in populations of spermatocytes and differentiated spermatids purified to near homogeneity by unit gravity sedimentation. Fractions covering the entire gradient were analysed resulting in a more accurate picture of the precise timing of expression than previously reported. Transcription of all three genes was up-regulated in pachytene primary spermatocytes and persisted at stable levels through the haploid spermatid stages. Significantly, only levels of mRNA encoded by D17Leh66, the candidate gene for Tcr, increased from early round to elongating-stage spermatids. If this pattern of expression does, in fact, represent Tcr, these data provide the first direct evidence that wild-type and t-haplotype Tcr elements could be differentially expressed in haploid spermatids. PMID- 2272511 TI - Yeast artificial chromosomes: an alternative approach to the molecular analysis of mouse developmental mutations. AB - Mammalian genetics now allows a molecular study of genomic regions previously analysed by genetic and embryological techniques. To simplify such an analysis, we have established a number of libraries of mouse DNA in Yeast Artificial Chromosome (YAC) vectors, constructed either by partial digestion with EcoRI, or by complete digestion with enzymes which cut rarely in the mammalian genome. In this paper we report the construction of complete digest libraries prepared from mouse genomic DNA using the rare cutter enzymes NotI and BssHII, and the detection of gene loci from the H-2 complex, the t-complex, and other loci from the mouse genome. Due to their large insert size, YAC clones simplify the cloning of extended regions of the mouse genome surrounding known developmental mutations and should, after introduction into the germ line, offer a high probability of correct expression of the genes contained within the cloned region. We hope that this will allow the use of YAC clones to scan regions of interest such as the t complex for specific genes by testing DNA introduced into transgenic mice for the ability to complement mutations localised to this region. PMID- 2272512 TI - Use of triple tissue blastocyst reconstitution to study the development of diploid parthenogenetic primitive ectoderm in combination with fertilization derived trophectoderm and primitive endoderm. AB - Diploid mouse conceptuses lacking a paternal genome can form morphologically normal but small fetuses of up to 25 somites, but they invariably fail to develop beyond mid-gestation. Such conceptuses differ from normal most notably in the poor development of extra-embryonic tissues which are largely of trophectodermal and primitive endodermal origin. However, it is not clear whether the demise of diploid parthenogenetic (P) or gynogenetic (G) conceptuses is attributable entirely to the defective development of these two tissues or whether differentiation of the primitive ectoderm, the precursor of the foetus, extra embryonic mesoderm and amnion, is also impaired by the absence of a paternal genome. Therefore, a new blastocyst reconstitution technique was used which enabled primitive ectoderm from P blastocysts to be combined with primitive endoderm and trophectoderm from fertilization-derived (F) blastocysts. One third of the 'triple tissue' reconstituted blastocysts that implanted yielded foetuses. However, all foetuses recovered on the 11th or 12th day of gestation were small and, with one exception, either obviously retarded or arrested in development. The exception was a living 44 somite specimen which is the most advanced P foetus yet recorded. Foetuses were invariably degenerating in conceptuses recovered on the 13th day. In contrast, at least 16% of control reconstituted blastocysts with primitive ectoderm as well as primitive endoderm and trophectoderm of F origin developed normally on the 13th day of gestation or to term. Hence, the presence of a paternal genome seems to be essential for normal differentiation of all 3 primary tissues of the mouse blastocyst. The P foetuses that developed from reconstituted blastocysts were so closely invested by their membranes that they often showed abnormal flexure of the posterior region of the body. Several also showed a deficiency of allantoic tissue. Therefore, the possibility that the defect in development of P primitive ectoderms resided in their extra-embryonic tissues was investigated by analysing a series of chimaeras produced by injecting them into intact F blastocysts. The foregoing anomalies were not discernible even when P cells made a large contribution to the extra-embryonic mesoderm or amnion plus umbilical cord. Furthermore, selection against P cells was no greater in extra-embryonic derivatives of the primitive ectoderm than in the foetus itself. PMID- 2272514 TI - Genome imprinting phenomena on mouse chromosome 7. AB - Heterozygotes for the reciprocal translocation T(7;15)9H were intercrossed, with albino (c) and underwhite (uw) as genetic markers, in order to study genetic complementation in mouse chromosome 7. Chromosome 15 is known to show normal complementation. Neither reciprocal cross in which one parent was c/c and the other wild type yielded albino progeny at birth although about 17% would be expected, but albino foetuses were recovered when the mother was c/c and father wild type. These products of maternal duplication/paternal deficiency for distal 7 were markedly retarded with small placentae. No albino foetuses were found when the father was c/c and mother wild type, which suggested earlier lethality. Equivalent crosses with uw (chromosome 15) as proximal marker gave normal underwhite progeny when the mother was uw/uw but small placentae, retardation and neonatal death of presumptive underwhites in the reciprocal cross. These abnormal newborn would have had a maternal duplication/paternal deficiency for proximal 7. These and other findings indicate that one region of defective complementation probably lies distal to the breakpoint of T(7;18)50H at 7E2-F2, while another is between the centromere and 7B3. Examination of man-mouse homologies suggests that the loci for three pathological human conditions (Beckwith-Weidemann syndrome, dystrophia myotonia and rhabdomyosarcoma) with differential parental transmission may be located in homologous regions to those affected by imprinting phenomena on mouse chromosome 7. PMID- 2272513 TI - Death of mouse embryos that lack a functional gene for glucose phosphate isomerase. AB - A null allele of the Gpi-1s structural gene, that encodes glucose phosphate isomerase (GPI-1; E.C. 5.3.1.9), arose in a mutation experiment and was designated Gpi-1sa-m1H. The viability of homozygotes has been investigated. No offspring homozygous for the null allele were produced by intercrossing two heterozygotes, so the homozygous condition was presumed to be embryonic lethal. Embryos were produced by crossing Gpi-1sa/null heterozygous females and Gpi 1sb/null heterozygous males. Homozygous null embryos were identified at different stages of development by electrophoresis and staining either for GPI-1 alone or GPI-1 plus phosphoglycerate kinase (PGK) activity. At 6 1/2 and 7 1/2 days post coitum homozygous null embryos were present at approximately the expected 25% frequency (37/165; 22.4% overall) although at 7 1/2 days the homozygous null embryos tended to be small. By 8 1/2 days most homozygous null embryos were developmentally retarded and had not developed significantly further than at 7 1/2 days; some were dead or dying. By 9 1/2 days the homozygous null conceptus was characterised by a small implantation site that contained trophoblast and often a small amount of extraembryonic membrane. Surviving trophoblast tissue was also detectable at 10 1/2 days. Previous studies have shown that oocyte-coded GPI 1 persists only until 5 1/2 or 6 1/2 days. Survival of homozygous null embryos to 7 1/2 or 8 1/2 days and survival of certain extraembryonic tissue to 10 1/2 days suggests that the homozygous null condition may not be cell-lethal although it is certainly embryo-lethal. Mutant cells that are deficient in glycolysis may use the pentose phosphate shunt to bypass the block in glycolysis created by the deficiency of glucose phosphate isomerase, and/or might be rescued by the transport, from the maternal blood, of energy sources other than glucose (such as glutamine). Either strategy may only permit slow cell growth that would not be adequate to support normal embryogenesis. Transport of maternal nutrients would be more efficient to the trophoblast and extraembryonic membranes and this may help to explain why these tissues survive for longer than the embryo itself. The morphological similarity between homozygous nulls and androgenetic conceptuses, where the trophoblast also survives better than the embryo, is discussed. PMID- 2272515 TI - Parental influences on expression of glucose-6-phosphate dehydrogenase, G6pd, in the mouse; a case of imprinting. AB - Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in blood from heterozygotes for the normal allele G6pda and the low activity allele G6pda mlNeu. In adult mice lower activity was found in G6pda/G6pda-mlNeu than in the reciprocal heterozygote G6pda-mlNeu/G6pda (the maternal allele being listed first). Thus, either the paternally derived allele was over-expressed or the maternally derived allele was under-expressed. By contrast, in younger mice the difference in G6PD activity in reciprocal crosses was less marked. The findings are interpreted in terms of differential imprinting of maternally and paternally inherited information. The explanation offered for age related differences is that, as a consequence of imprinting, either the paternal X-chromosome is preferentially reactivated, or cells in which the paternally derived allele is active are at a selective advantage, and proliferate better than those in which the maternally inherited allele is active. PMID- 2272516 TI - Genome cryopreservation: a valuable contribution to mammalian genetic research. AB - Mouse embryo banking has become an important asset to geneticists. Individual laboratories can now maintain a far greater diversity of stocks than by conventional breeding alone. Also, many mutations that in the past would have been discarded due to lack of space, can now be preserved for future use. Recent advances in cryopreservation techniques have simplified procedures and, in certain cases, resulted in increased rates of survival. PMID- 2272517 TI - Genetics of alcohol dehydrogenase and aldehyde dehydrogenase from Monodelphis domestica cornea: further evidence for identity of corneal aldehyde dehydrogenase with a major soluble protein. AB - A didelphid marsupial, the gray short-tailed opossum (Monodelphis domestica), was used as a model species to study the biochemical genetics of alcohol dehydrogenases (ADHs) and aldehyde dehydrogenase (ALDH) in corneal tissue. Isoelectric point variants of corneal ALDH (designated ALDH3) and a major soluble protein in corneal extracts were observed among eight families of animals used in studying the genetics of these proteins. Both phenotypes exhibited identical patterns following PAGE-IEF and were inherited in a normal Mendelian fashion, with two alleles at a single locus (ALDH3) showing codominant expression. The data provided evidence for genetic identity of corneal ALDH with this major soluble protein, and supported biochemical evidence, recently reported for purified bovine corneal ALDH, that this enzyme constitutes a major portion of soluble corneal protein (Abedinia et al. 1990). Isoelectric point variants for corneal ADH were also observed, with patterns for the two major forms (ADH3 and ADH4) and one minor form (ADH5) being consistent with the presence of two ADH subunits (designated gamma and delta), and variant phenotypes existing for the gamma subunit. The genetics of this enzyme was studied in the eight families, and the results were consistent with codominant expression of two alleles at a single locus (designated ADH3). It is relevant that a major detoxification function has been proposed for corneal ADH and ALDH, in the oxidoreduction of peroxidic aldehydes induced by available oxygen and UV-B light (Holmes & VandeBerg, 1986a). In addition, a direct role for corneal ALDH as a UV-B photoreceptor in this anterior eye tissue has also been proposed (Abedinia et al. 1990). PMID- 2272518 TI - In honour of Mary Lyon. PMID- 2272519 TI - Mary Lyon: an appreciation. PMID- 2272520 TI - Insights into X chromosome inactivation from studies of species variation, DNA methylation and replication, and vice versa. AB - I am indebted to Mary Lyon as her X-inactivation hypothesis stimulated my mentor, Barton Childs, and in turn, myself, to think about the consequences of X inactivation in heterozygous females. I often reread her original papers setting forth the single active X hypothesis, and still marvel at the concise and compelling exposition of the hypothesis and the logical predictions which seemed prophetic at my first reading, and have survived the test of time. My contribution to this Festschrift reviews evidence derived from studies of DNA methylation, species variation and DNA replication that reveals an important role for methylated CpG islands and suggests a role for late DNA replication in propagating X inactivation from one cell to its progeny. These studies also show that X inactivation is a powerful research tool for identifying the factors which program and maintain developmental processes. PMID- 2272521 TI - The search for the mouse X-chromosome inactivation centre. AB - The phenomenon of X-chromosome inactivation in female mammals, whereby one of the two X chromosome present in each cell of the female embryo is inactivated early in development, was first described by Mary Lyon in 1961. Nearly 30 years later, the mechanism of X-chromosome inactivation remains unknown. Strong evidence has accumulated over the years, however, for the involvement of a major switch or inactivation centre on the mouse X chromosome. Identification of the inactivation centre at the molecular level would be an important step in understanding the mechanism of X-inactivation. In this paper we review the evidence for the existence and location of the X-inactivation centre on the mouse X-chromosome, present data on the molecular genetic mapping of this region, and describe ongoing strategies we are using to attempt to identify the inactivation centre at the molecular level. PMID- 2272522 TI - Influence of aging on ethanol and acetaldehyde oxidation in female rat liver. AB - Rates of ethanol metabolism by alcohol dehydrogenase, the microsomal ethanol oxidizing system (MEOS), and catalase were similar in liver preparations from young (4-5 months) and old (24-27 months) female Fischer 344 rats. On the other hand, rates of acetaldehyde metabolism by mitochondrial aldehyde dehydrogenase (ALDH) were 15-20% lower in livers of old rats than in those of younger ones. Results with the ALDH inhibitor cyanamide indicated that a decline in ALDH activity of this magnitude would not increase acute ethanol hepatotoxicity. PMID- 2272523 TI - Primitive reflexes and MRI findings, cerebral blood flow in normal elderly. AB - We studied the relation between primitive reflexes (glabellar, snout and palmomental) and MRI findings, cerebral blood flow and mental function in 68 normal aged volunteers. One or more of the three primitive reflexes was elicited in 50% of all subjects. The subjects who had the incidental cerebral lesions showed a significantly higher incidence of the primitive reflexes than those without them. However, there was no difference in mean regional cerebral blood flow (rCBF), brain atrophy and intellectual ability between the subjects with primitive reflexes and those without. The primitive reflexes appear in a significant proportion and these reflexes have a significant relationship with incidental cerebral lesions in normal elderly. PMID- 2272524 TI - Low serum ionized to total calcium ratio: association with geriatric diabetes mellitus and with other cardiovascular risk factors? AB - Serum total calcium concentrations (CaT) were increased, ionized calcium concentrations (CaI) normal, and the CaI/CaT ratios decreased in 125 geriatric diabetics as compared with 379 non-diabetic controls. In the whole population of 558 consecutive geriatric inpatients, the CaI/CaT ratios were inversely correlated with body weight, diastolic blood pressure and plasma glucose. The findings and calculations help to explain some inconsistencies and discrepancies in previous studies concerning calcaemia in diabetes, hypertension and the 'metabolic syndrome' of clustered risk factors for cardiovascular diseases. They also demonstrate that CaT and the 'correction' of CaT for serum albumin concentration can be biased in diabetes and other conditions closely associated with cardiovascular risks. Increased serum free fatty acids could at least in part explain low ratios. PMID- 2272526 TI - Should medical screening of the elderly population be promoted? AB - This article reviews the history of screening in the elderly, the conditions that should be considered, whether or not screening in the elderly is of benefit, whether we should look for disability or diseases and where screening should take place. Thirteen conditions are discussed: hearing loss and anaemia in some detail. Both disability and precise diagnostic criteria are considered. The place where screening is best carried out depends on the mobility of the subject and the nature of the particular screening tests selected for the 13 conditions. The desirability of screening was assessed on the following criteria: prevalence of the condition, severity of the problem, acceptability by the patient of the screening test, false positive rate, consequences of making a false positive diagnosis, the false negative rate and the consequences of this error, the effect of treatment, the cost of the screening test and the burden on the health services produced by the screening test. The criteria were scored 1-5 on a scale defined for each assessment, with higher scores favouring screening. We provide evidence that screening may be worthwhile for: need for chiropody, varicose veins/ulcer, hearing loss, obesity, visual impairment, hypothyroidism, hypertension, anaemia and diabetes mellitus. However, the assessments discussed in this paper need to be tested prospectively in randomised controlled trials. PMID- 2272525 TI - Analysis of cutaneous delayed-type hypersensitivity reaction and T cell proliferative response in elderly nursing home patients: an approach to identifying immunodeficient patients. AB - Clinical experience suggests the delayed-type hypersensitivity (DTH) skin test lacks sensitivity in assessing the integrity of systemic cell-mediated immunity (CMI) or the status of recent or remote mycobacterial infections in elderly nursing home residents. In an attempt to clarify this issue, DTH reaction to purified protein derivative (PPD), tetanus toxoid and Candida albicans was compared with circulating thymus-derived lymphocyte (T cell) proliferation (TCP) to stimulation with PPD and anti-CD3 antibody in 24 randomly selected nursing home residents. The DTH reaction and the TCP response correlated reasonably well among the DTH reactors but poorly among DTH nonreactors, suggesting there may be age-related immunologic changes in the skin itself. Also, the DTH skin test to PPD alone was found to be a poor index of the integrity of systemic CMI. PMID- 2272527 TI - Effects of 2,2'-azobis (2-amidinopropane) hydrochloride in vivo and protection by vitamin E. AB - 2,2'-Azobis (2-amidinopropane) hydrochloride (AAPH), a compound that decomposes spontaneously to generate free radicals, was administered intraperitoneally to rats. High doses (greater than or equal to 70 mg/kg) were always fatal within a few hours. At nonlethal levels, AAPH was found to be absorbed into the circulation where it remained with a half-life of about 30 min. Lipid peroxidation was observed to occur in the liver and, to a much smaller extent, the kidney and heart of treated rats; levels of thiobarbituric acid-reactive substances were unchanged in the lung and brain, and significantly reduced in the plasma. Serum lipid levels were also lower in the AAPH-treated rats. Orally administered vitamin E, but not its water soluble analog, prevented the accumulation of TBA-reactive substances in the livers of AAPH-treated rats in a dose-dependent manner, but had no effect on mortality or the changes in serum lipid levels. The data suggest that intraperitoneally administered AAPH is absorbed into the circulation and can induce lipid peroxidation in vivo, but that toxicity may also arise through nonradical mechanisms. Furthermore, the free radical toxicity of AAPH in vivo may not be so general as previously suggested. PMID- 2272528 TI - Is methyl-branching in alpha-tocopherol's "tail" important for its in vivo activity? Rat curative myopathy bioassay measurements of the vitamin E activity of three 2RS-n-alkyl-2,5,7,8-tetramethyl-6-hydroxychromans. AB - The vitamin E activity of the acetates of three 2RS-n-alkyl-2,5,7,8-tetramethyl-6 hydroxychroman analogs of alpha-tocopherol have been measured and compared directly with all-rac-alpha-tocopheryl acetate, or indirectly via 2R,4'R,8'R alpha-tocopheryl acetate, using the rat curative myopathy, plasma pyruvate kinase assay. The analogs with alkyl chain lengths of 11 and 13 carbons have activities which not only do not differ significantly (p greater than 0.05) from each other but also do not differ from that of all-rac-alpha-tocopheryl acetate. This finding indicates that methyl branching in the phytyl tail at the 4', 8', and 12' positions has little if any influence upon vitamin E activity. Thus physical interactions involving the methyl branches of the phytyl tail and the polyunsaturated moieties of membrane phospholipids are unimportant in vivo, insofar as this bioassay is concerned. However, the length of the hydrocarbon tail is important. This is indicated by the result obtained with the acetate of the analog with an alkyl chain length of 15 carbon atoms which had only 15% of the activity of 2R,4'R,8'R-alpha-tocopheryl acetate, i.e., 22% of the activity of all-rac-alpha-tocopheryl acetate since this form is 1.47 times less active than 2R,4'R,8'R-alpha-tocopheryl acetate in the curative myopathy bioassay (Weiser, Vecchi, & Schlachter, Internat. J. Vit. Nutr. Res. 55:149-158, 1985). PMID- 2272530 TI - What is in a name? Rules for radicals. PMID- 2272529 TI - Hypoxia/reoxygenation increases the permeability of endothelial cell monolayers: role of oxygen radicals. AB - We assessed the effect of hypoxia/reoxygenation on 14C-albumin flux across endothelial monolayers. Cultured bovine pulmonary artery endothelial cells were grown to confluence on nitrocellulose filters (pore size 12 microns). The endothelialized filters were mounted in Ussing-type chambers which were filled with cell culture medium (M 199). Equimolar amounts (33 nM) of 14C-labeled and unlabeled albumin were added to the "hot" and "cold" chambers, respectively. The monolayers were then exposed to successive periods (90 min) of normoxia (pO2 145 mmHg), hypoxia (pO2 20 mmHg), and reoxygenation (pO2 145 mmHg). A gas bubbling system was used to control media pO2 and to ensure adequate mixing. Four aliquots of culture media were taken during each period in order to calculate the 14C albumin permeability across the endothelialized filter. In some experiments, either the xanthine oxidase inhibitor, oxypurinol (10 microM), or superoxide dismutase (600 U/mL), was added to the media immediately prior to the experiments. As compared to the normoxic control period, albumin permeability was 1.5 times higher during hypoxia (p less than 0.01) and 2.3 times higher during reoxygenation (p less than 0.01). The reoxygenation-induced increase in albumin permeability was prevented by either oxypurinol or superoxide dismutase. These data indicate that xanthine oxidase-derived oxygen radicals contribute to the hypoxia/reoxygenation-induced endothelial cell dysfunction. The altered endothelial barrier function induced by hypoxia/reoxygenation is consistent with the microvascular dysfunction observed following reperfusion of ischemic tissues. PMID- 2272531 TI - MRI detection of hyperoxia-induced lung edema in Zn-deficient rats. AB - In a pioneering application of proton Magnetic Resonance Imaging (MRI), lung edema has been monitored in vivo in Zn-deficient rats exposed to 85% oxygen. Dietary Zn appears to play a role in protecting against hyperoxia-induced lung damage. PMID- 2272532 TI - Reactive oxygen species and airway inflammation. AB - Reactive oxygen species may be generated by several inflammatory cells which participate in airway inflammation and their production may be increased in asthma. Oxygen metabolites may contribute to the epithelial damage which is characteristic of asthmatic airways and may activate cells such as mast cells in the airway mucosa. Reactive oxygen species may cause bronchoconstriction, mucus secretion, have effects on airway vasculature, and may increase airway responsiveness. The role of reactive oxygen species in airway disease has been largely neglected, but appears to be an important area for future study. It is also possible that antioxidant defenses may be defective in asthma. If reactive oxygen species participate in the inflammatory response in airway disease, then radical scavengers or antioxidants could play a useful role in therapy. PMID- 2272533 TI - Biochemical basis of ozone toxicity. AB - Ozone (O3) is the major oxidant of photochemical smog. Its biological effect is attributed to its ability to cause oxidation or peroxidation of biomolecules directly and/or via free radical reactions. A sequence of events may include lipid peroxidation and loss of functional groups of enzymes, alteration of membrane permeability, and cell injury or death. An acute exposure to O3 causes lung injury involving the ciliated cell in the airways and the type 1 epithelial cell in the alveolar region. The effects are particularly localized at the junction of terminal bronchioles and alveolar ducts, as evident from a loss of cells and accumulation of inflammatory cells. In a typical short-term exposure the lung tissue response is biphasic: an initial injury-phase characterized by cell damage and loss of enzyme activities, followed by a repair-phase associated with increased metabolic activities, which coincide with a proliferation of metabolically active cells, for example, the alveolar type 2 cells and the bronchiolar Clara cells. A chronic exposure to O3 can cause or exacerbate lung diseases, including perhaps an increased lung tumor incidence in susceptible animal models. Ozone exposure also causes extrapulmonary effects involving the blood, spleen, central nervous system, and other organs. A combination of O3 and NO2, both of which occur in photochemical smog, can produce effects which may be additive or synergistic. A synergistic lung injury occurs possibly due to a formation of more powerful radicals and chemical intermediates. Dietary antioxidants, for example, vitamin E, vitamin C, and selenium, can offer a protection against O3 effects. PMID- 2272534 TI - Defective CSA-dependent granulopoiesis in patients with chronic drug-induced neutropenia. AB - Colony stimulating activity (CSA) and granulocyte-macrophage progenitor cells (GM CFC) were assayed in the bone marrow and peripheral blood of 17 patients with drug-induced chronic neutropenia. Leukocyte-derived and monocyte/macrophage derived CSA from the neutropenic patients was found to be significantly decreased compared to normal control. However, bone marrow and peripheral blood GM-CFC were within normal limits. These data suggest that in neutropenic patients monocyte/macrophages exhibit most likely a qualitative defect in CSA production, which may account at least in part, for the impaired granulopoiesis observed in drug-induced neutropenia. PMID- 2272535 TI - Does human bladder carcinoma cell line 5637-conditioned medium supplement the growth of megakaryocyte colonies (CFU-Mk) in cultures of human bone marrow? PMID- 2272536 TI - Changes in nucleolar morphology during macrophage development in non-Hodgkin's lymphoma: a morphometric study. AB - Nucleolar ultrastructure of macrophages developing in suspension culture from monocytes was studied in 20 patients with non-Hodgkin's lymphoma and 20 normal subjects. Morphometric measurements of nucleolar volume, surface area, volume fraction, surface-to-volume ratio and number of profiles per section were made over a 6 day period. Multivariate analysis of variance showed that culture time and subject group had significant effects: changes during macrophage development were less marked in the patient group, nucleoli were fewer, rounder and possibly smaller than normal. The results indicate disturbed macrophage development in non Hodgkin's lymphoma and may be related to mononuclear phagocyte dysfunction. PMID- 2272537 TI - The effect of monocytic involvement of hyperaldolasaemia in patients with acute myelogenous leukaemia. AB - Serum aldolase concentrations were determined in 78 patients with acute myelogenous leukaemia (AML). Mean serum aldolase concentration (+/- SD) at the time of diagnosis was 28.3 U/L (+19.4). 71.8% of AML patients had increased serum aldolase concentrations. The highest hyperaldolasaemia were observed in patients with acute myelomonocytic leukaemia and acute monoblastic leukaemia. The monocytic involvement in AML patients was significantly related to serum aldolasaemia. Human aldolase gene has been located on chromosome 16, whose structural aberrations are frequent in AML patients with monocytic involvement, explaining the link between serum hyperaldolasaemia and the monocytic involvement in AML patients. PMID- 2272538 TI - Phytohaemagglutinin-induced neutrophil aggregation in patients affected by chronic myeloproliferative diseases. AB - The aim of this work was to evaluate the phytohaemagglutinin-induced aggregation of circulating neutrophils isolated from 25 patients affected by chronic myeloproliferative syndromes (polycythaemia vera, chronic myeloid leukaemia in chronic phase, and essential thrombocythaemia). The results showed a lesser aggregating capacity in chronic myeloid leukaemia (CML) and an opposite behaviour in polycythaemia vera and essential thrombocythaemia. Patients with polycythaemia vera whose neutrophils showed a greater aggregating capacity were shown to have had various vascular complications. PMID- 2272539 TI - Complement-mediated immune complex solubilization and precipitation inhibition in sera of patients with non-Hodgkin's lymphoma. AB - The complement functions of 42 patients with non-Hodgkin's lymphoma have been examined. The patients were divided into groups according to the severity of their disease: 1st--patients with high-grade lymphomas, 2nd--with low-grade lymphomas and 3rd--with chronic lymphocytic leukaemia. The adopted methods were the measurements of complement-mediated immune complex solubilizing capacity (CMSC) and the complement-mediated immune complex precipitation inhibition capacity (IPIC). The CMSC and IPIC values were examined parallel with CH50, C3 complement levels and with levels of circulating immune complexes (CIC) in the sera of patients. The results indicated that the acquired deficiency of complement functions could be established by CMSC and IPIC measurements in the sera of patients with high-grade lymphomas. These defects were found to be milder in the group with low-grade lymphomas, and were not detectable in CLL. The changes of CH50 levels were found to be similar to that of IPIC values and the decrease in C3 levels was detectable in high-grade and low-grade lymphomas too. Elevated CIC levels were found in those cases in which both CMSC and IPIC were decreased. PMID- 2272540 TI - [Effects of aging and the autonomic nervous system-related agents on the intravesical pressure of the bladder in situ in female rats]. AB - We investigated the effects of several autonomic nervous system-related agents on the intravesical pressure (IVP) in adult (11-23 weeks old, 200-350 g) and aged (2 years old, 350-770 g) female rats. Acetylcholine induced a dose-dependent and transient increase of IVP, which was competitively antagonized by pirenzepine weakly and by atropine strongly. These results suggest the predominance of M-2 receptors. Adrenaline induced dual actions of decrease and increase of IVP at low and high doses, respectively. Adrenaline (at only high doses), noradrenaline and phenylephrine increased IVP but not clonidine, suggesting the predominance of alpha-1 receptors. Isoproterenol, salbutamol and clenbuterol decreased IVP to same extent and the effect of isoproterenol was markedly antagonized by propranolol and slightly by atenolol, suggesting the predominance of beta-2 receptors. ATP increased IVP dose-dependently but not adenosine, suggesting the predominance of P-2 receptors. Serotonin and prostaglandin F2 alpha also increased IVP. In aged rats, the maximal response to acetylcholine was lower than in adult rats and the decrease in IVP by low doses of adrenaline was not observed. These results suggest that the increase of IVP involves the participation of cholinergic M-2 receptors to a large extent and also serotonergic, adrenergic alpha-1 and purinergic P-2 receptors to some extent and that the responsiveness to acetylcholine is reduced by ageing. PMID- 2272541 TI - [Physiological and pharmacological actions of a neuroactive dipeptide, kyotorphin, and its precursor, L-arginine, and clinical application]. AB - This review describes: 1. Recent findings about the physiological and pharmacological actions of kyotorphin that was isolated from the brain. 2. Biosynthesis, distribution, release, uptake, enzymatic destruction of this peptide in the body. 3. L-Arginine was found to be a precursor of kyotorphin. 4. Clinical application of the precursor to the treatment of chronic pain. PMID- 2272542 TI - [Effects of lactulose on blood ammonia levels in beagles with end-to-side portacaval shunt]. AB - The effects of lactulose on blood ammonia and fecal pH in beagles with an end-to side portacaval shunt were investigated. Concentrations of blood ammonia before and two weeks after the operation were 4.65 +/- 0.34 micrograms/ml (N = 12) and 8.66 +/- 0.60 micrograms/ml (N = 6), respectively (P less than 0.01), while there was no significant difference in fecal pH values before and after the operation. The blood ammonia concentrations in the control and lactulose-treated (2.1 g/kg, p.o.) groups after administration of meat were 12.65 +/- 1.64 micrograms/ml (N = 8) and 8.45 +/- 0.90 micrograms/ml (N = 8), respectively (P less than 0.05). The fecal pH values in the control and lactulose-treated (2.1 g/kg, p.o.) beagles were 6.24 +/- 0.09 (N = 8) and 5.58 +/- 0.08 (N = 8), respectively (P less than 0.01). The lowering effect of lactulose on the blood ammonia levels could not be ascribed to its laxative action alone, because the oral administration of lactulose at doses less than 2.1 g/kg induced no fluid evacuation. The present studies in the beagle suggest that the action of lactulose produce a lowering of fecal pH, causing an increase in the concentration of less absorbable ammonium ions and a decrease in the production of toxic nitrogenous compounds such as ammonia, resulting in a reduction in blood ammonia levels. PMID- 2272543 TI - Strategies for toxicity testing of food chemicals and components. PMID- 2272544 TI - Shortcomings of current strategy for toxicity testing of food chemicals: polyols. PMID- 2272545 TI - Shortcomings of current strategy for toxicity testing of food chemicals: antioxidants. PMID- 2272546 TI - Issues to be considered in the safety evaluation of fat substitutes. PMID- 2272547 TI - Safety evaluation of hydrogenated oils. PMID- 2272548 TI - Solanine (glycoalkaloids) in potatoes: toxicological evaluation. PMID- 2272549 TI - Health effects of dietary selenium. PMID- 2272550 TI - Mechanistic studies in man, laboratory animals and in vitro systems. PMID- 2272551 TI - Safety studies in humans. I: Studies on food ingredients. PMID- 2272552 TI - Safety studies in humans. II: Human volunteer studies. PMID- 2272553 TI - Relevance of endpoints in toxicity testing of food ingredients. PMID- 2272554 TI - A viewpoint on the extrapolation of toxicological data from animals to man. PMID- 2272555 TI - Current guidelines for toxicity testing: their strengths and weaknesses. PMID- 2272556 TI - Reproductive toxicology and nutritional studies on mahua oil (Madhuca latifolia). AB - Mahua (Madhuca latifolia, Sapotaceae) seed oil is a common ingredient of hydrogenated fat in India. It is obtained from the seed kernels (which contain 45% oil, w/w), and is a pale yellow, semi-solid fat at room temperature. It has palmitic (19%), stearic (15%), oleic (42%) and linoleic (24%) as a major fatty acids. The physicochemical parameters of the oil are similar to those of other edible oils. The unsaponifiable fraction contains several unidentified polyenes. Nutritional studies were carried out in groups of 15 weanling albino rats of each sex, fed for 14 wk on a 20% protein diet, adequate in all vitamins and minerals, containing 10% mahua oil. A similar (control) group was simultaneously maintained on the same basic diet containing 10% groundnut oil. The growth, fat absorption, and retention of nitrogen, calcium and phosphorus were similar in the two groups, as were the lipid profiles of the serum, liver and heart. Multigeneration reproduction studies in groups of 15 rats of each sex, fed a diet containing 10% mahua oil, as used in the above study, indicated poor reproductive performance in the second generation. All the male rats became sterile. Histological studies indicated bilateral testicular atrophy with degenerative changes in the seminiferous tubules in the affected animals. On withdrawal of mahua oil from the diet and rehabilitation, the male animals regained their fertility. These results indicate temporary male sterility on feeding mahua oil to rats. No other adverse toxicological effects were found. PMID- 2272557 TI - A study of the mutagenicity of some commercially canned Spanish mushrooms. AB - The mutagenicity of two wild (Lactarius deliciosus and Boletus luteus) and two cultivated (Agaricus bisporus and Pleurotus ostreatus) mushrooms, preserved by canning and widely consumed in Spain, was studied in the Ames Salmonella/microsome test and in the CHO/HPRT assay system using mammalian cells. The mushroom extracts did not show mutagenicity in the microbial Ames test nor in the mammalian CHO-K1 cells, and this response was not modified by the presence of S-9 mix in the assay mixtures. Only the extracts from P. ostreatus showed a weak mutagenic activity in the CHO/HPRT assay in the presence of a metabolic activation system (S-9). PMID- 2272558 TI - Carcinogenicity study of methyl hesperidin in B6C3F1 mice. AB - A long-term carcinogenicity study of methyl hesperidin, a compound of the vitamin P group, was carried out in B6C3F1 mice receiving dietary concentrations of 0, 1.25 or 5%. Administration was continued for 96 wk and then the mice were maintained on basal diet for an additional 8 wk. Growth retardation during the experiment with final changes in organ weights were observed in females given the 1.25% dose of methyl hesperidin and in both sexes receiving the 5.0% treatment. However, no biologically significant effects were evident with respect to mortality or clinical signs. Furthermore, treatment with methyl hesperidin did not result in any changes in haematology, clinical chemistry and urinalysis data. On histological examination, no significant alteration of non-neoplastic and neoplastic lesion incidence was observed in treated mice. The results thus demonstrated that methyl hesperidin lacked any carcinogenicity for B6C3F1 mice in the 96-wk feeding regimen used in this study. PMID- 2272559 TI - The migration of tobacco-specific nitrosamines into the saliva of chewers of nicotine-containing chewing gum. AB - In many countries nicotine-containing chewing gum (Nicorette) is used to help to break the habit of smoking. Saliva was collected every 5 min from chewers of nicotine chewing gum and analysed for tobacco-specific nitrosamines. Detectable levels of tobacco-specific nitrosamines were found in all samples collected between 5 and 15 min after chewing had started. The levels of N' nitrosonornicotine ranged from 0.4 to 19 ng/g of saliva and those for the sum of N'-nitrosoanatabine plus N'-nitrosoanabasine from 1.3 to 46 ng/g. 4-(N-methyl-N nitrosamino)-1-(3-pyridyl)-1-butanone was not detected in the saliva. The nicotine chewing gum was found to contain up to 380 ng tobacco-specific nitrosamines/g of chewing gum. PMID- 2272560 TI - 4-week oral toxicity study of a combination of eight chemicals in rats: comparison with the toxicity of the individual compounds. AB - In a 4-wk oral toxicity study, 4-wk-old male and female Wistar rats were exposed to a combination of arbitrarily chosen chemicals comprising sodium metabisulphite, Mirex, Loperamide, metaldehyde, di-n-octyltin dichloride, stannous chloride, lysinoalanine and potassium nitrite. The dose levels used were based on the "no-observed-adverse-effect level" (NOAEL) and the "minimum-observed adverse-effect level" (MOAEL) of the individual compounds obtained in similar studies with Wistar rats previously performed at TNO-CIVO, and comprised 0 (controls), 1/10 and 1/3 of the NOAEL, the NOAEL and the MOAEL. In comparison with the adverse effects of the individual compounds, both more severe and less severe adverse effects were observed at the MOAEL of the combined compounds, indicating interaction of effects at this exposure level. Slightly decreased haemoglobin content and slightly increased relative kidney weight were the only treatment-related adverse effects seen in the NOAEL group. In the 1/10 and 1/3 NOAEL groups no untoward effects were found that could be related to treatment. The present study clearly demonstrates absence of a simple additive effect, and provides some, but no convincing, evidence for an increased risk from exposure to a combination of chemicals when each chemical is administered at its own individual NOAEL. At lower dose levels no increased risk appears to exist. These generalizations may not be fully justifiable from a purely scientific point of view but are the most important practical lesson learnt from the present study. PMID- 2272561 TI - Inhibition by coffee of nitrosourea-mediated DNA damage in mice. AB - Oral administration of coffee at doses ranging from 150 mg to 1 g per kg body weight significantly decreased endogenously formed nitrosourea-mediated DNA damage in bone marrow as well as in colon epithelial cells in mice that had simultaneously received oral administration of methylurea and sodium nitrite. Since coffee (1 g/kg body weight) did not decrease DNA damage when administered orally together with performed methylnitrosourea, it was hypothesized that coffee inhibits nitrosation in the stomach of mice. The lowest effective level of coffee, when compared on the basis of body weight, corresponds to a human intake of about 5 cups of coffee. Both chlorogenic acid (150 mg/kg body weight) and premelanoidins (1 g/kg body weight), which occur as ingredients in, or are formed during roasting of, coffee, were shown to inhibit nitrosourea-induced DNA damage in mice. PMID- 2272562 TI - Comparative studies of the mutagenicity of urine from smokers and non-smokers on a controlled non-mutagenic diet. AB - Measuring the mutagenicity of urine is widely viewed as a means of evaluating human exposure to potentially genotoxic materials. Diet and cigarette smoking have both been reported to affect the mutagenicity of human urine, but the relationship between smoking status and the expression of diet-related urinary mutagenicity is unknown. It has been reported that some promutagens are more active in in vitro assays when tested in the presence of urine from smokers than when tested in the presence of urine from non-smokers. We aimed to determine whether the differences in urinary mutagenicity between smokers and non-smokers result from increased urinary mutagenicity from dietary heterocyclic amine mutagens in smokers compared with non-smokers. Groups of smokers and non-smokers (6-12) were given identical diets, previously shown to be low in heterocyclic amines and very low in mutagenicity. The diet consisted exclusively of raw food and of food cooked in boiling water. After a 2-day dietary stabilization period, 24-hour urine samples were collected for three consecutive days. The regimen was repeated in the following week. For comparison, both groups were also placed on a "western" diet, consisting of a variety of foods prepared by several cooking methods, designed to reflect what a typical United States family might consume. Urine was concentrated using XAD-2 resin and then assayed for mutagenic activity in the Ames test. The urine of smokers was significantly more mutagenic than that of non-smokers when on both the raw/boiled and the "western" diets. These results indicate that the increased urinary mutagenicity observed in smokers compared with non-smokers is not due to enhanced mutagenicity of diet-related heterocyclic amine mutagens in the urine of smokers. PMID- 2272564 TI - Photosensitizing potential of benzanthrone. AB - In skin-photosensitization studies on guinea-pigs benzanthrone induced significant erythema and oedema, depending upon the doses both of benzanthrone and of sunlight or artificially simulated UVA radiation. Maximum sensitization and delayed tanning response on the guinea-pig skin were observed 24-36 hr after irradiation. Photosensitized benzanthrone was found to produce significant amounts of singlet oxygen in vitro, as assessed by the bleaching of N,N-dimethyl p-nitrosoaniline. As with haematoporphyrin and rose bengal, both of which are potent generators of singlet oxygen, the production of singlet oxygen by benzanthrone was dependent on both the concentration of the test chemical and the dose of solar radiation. Benzanthrone also produced a significant yield of superoxide anion radicals on exposure to simulated solar radiation or sunlight. Photosensitized benzanthrone induced photohaemolysis of rat erythrocytes and lipid peroxidation of erythrocyte ghosts, in vitro, probably largely through involvement of singlet oxygen (1O2). The rate of lipid peroxidation by photosensitized benzanthrone was inhibited by 64-80% with 1,4 diazabicyclo(2,2,2)octane and sodium azide, 15% with superoxide dismutase but was not affected by mannitol and sodium benzoate. Equimolar concentrations of haematoporphyrin and rose bengal also produced considerable photohaemolysis of erythrocytes and lipid peroxidation in erythrocyte ghosts; in both cases rose bengal was the most active and benzanthrone the least active of the three compounds. PMID- 2272563 TI - Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins. AB - 3-Nitrotyrosine (NTYR) in tissue or blood proteins was evaluated as a possible exposure marker for exogenous and endogenous nitrosating or nitrating agents. A sensitive and selective method for analysing NTYR by gas chromatography with a thermal energy analyser (GC-TEA) was developed. Using this method, a number of kinetic studies were carried out. It was found that free and protein-bound tyrosine residues easily react with nitrating/nitrosating agents to yield NTYR. NTYR formation in vivo showed a dose-dependent increase in NTYR in both plasma proteins and haemoglobin obtained from rats 24 hr after ip injection of various doses (0.5-2.5 mumol/rat) of tetranitromethane. Major urinary metabolites of NTYR, given orally to rats, were isolated and identified as 3-nitro-4 hydroxyphenylacetic acid (NHPA) and 3-nitro-4-hydroxyphenyllactic acid (NHPL). About 44% and 5% of the oral dose of NTYR (100 micrograms/rat) was excreted as NHPA and NHPL, respectively. Eleven 24-hr human urine samples were analysed for NHPA by GC-TEA after ethyl acetate extraction and HPLC purification: quantities ranging from 0 to 7.9 micrograms/24 hr, mean +/- SD 2.8 +/- 2.3 (n = 11) were detected (detection limit 0.2 micrograms/litre). NTYR in proteins or its metabolites in urine can be readily analysed by GC-TEA as a new/additional marker for endogenous nitrosation and nitration. PMID- 2272566 TI - The bad news about the British diet. PMID- 2272565 TI - Meeting report: industrial genetic toxicology discussion group. PMID- 2272567 TI - [Drusen and their significance in age related macular degeneration]. AB - In 81 patients with bilateral drusen and 150 patients with unilateral disciform lesions drusen were analyzed with respect to number, size, density and early and late angiographic behavior. In patients with bilateral drusen excellent symmetry was observed for all parameters. Drusen in fellow eyes of patients with avascular pigment epithelium detachments were larger, more confluent and less fluorescent than drusen in fellow eyes of patients with choroidal neovascularization. These results reveal drusen as products of specific metabolic failures of the pigment epithelium rather than unspecific aging changes. These metabolic failures result in specific individual patterns of drusen, which predispose to the development of specific complications of age-related macular degeneration. PMID- 2272568 TI - [Occlusive retinal vasculopathy with subsequent secondary glaucoma. Demonstration of typical findings and therapeutic references]. AB - The etiology of occlusive vascular retinopathy with subsequent neovascular glaucoma has not been clarified even today. If not diagnosed in the early stage therapy is often unsuccessful. Men and women aged between 35 and 65 years are affected with equal frequency. In a group of nine patients presenting at our clinic within three years four had irreversible functional loss by the time of the initial examination. In eyes with better visual function at the time of diagnosis only minimal vision and visual field can be preserved. Even this is only possible with intensive therapeutic efforts. Besides a rapid diagnosis to exclude prior vascular processes that can be treated areas of the retina with reduced perfusion always need to be treated by means of cryo- or lasercoagulation. Adjacently inhibitors of thrombocyte-aggregation to improve perfusion should be administered. Any delay of coagulation should be avoided since resulting secondary glaucoma is very difficult to treat. PMID- 2272570 TI - [Lens opacities after pars plana vitrectomy in diabetic vitreoretinopathy and macular pucker]. AB - The incidence of lens opacities reported after pars plana vitrectomy for various indications for vitrectomy has varied considerably. Comparison of the different indications for vitrectomy is only partially possible because of a lack of comparable studies. In this prospective study the indications for vitrectomy were investigated: macular pucker and diabetic vitreoretinopathy were compared concerning the postoperative incidence of lens opacities. Nearly twice as many cases of lens opacity occurred after vitrectomy for diabetic retinopathy. Also, the fellow eyes of the patients with diabetic vitreoretinopathy developed lens opacity much more frequently after vitrectomy compared with the fellow eyes of the patients with macular pucker. PMID- 2272569 TI - [Retinitis pigmentosa and sensory atactic polyneuropathy with reduction of apolipoprotein B]. AB - In this paper we discuss a female patient with retinitis pigmentosa. Pronounced pigmentation in the periphery, together with yellow waxlike optical atrophy and contracted arteries, characterized the ophthalmological findings. The ERG was extinguished. The neurological examination revealed preponderantly atactical polyneuropathy accompanied by primary axonal degeneration. Chemical laboratory values indicated a reduction in apolipoprotein B in the patient and in her children as well, who showed no clinical symptoms. PMID- 2272571 TI - [Vitrectomy in proliferative diabetic retinopathy. Preoperative factors for surgical procedure and postoperative results]. AB - In this study we evaluated the impact of preoperative factors on the choice of intraocular tamponades (balanced salt solution and gas or silicone oil) and postsurgical visual function in cases of vitrectomy for proliferative diabetic retinopathy. We studied 150 consecutive vitrectomies for proliferative diabetic retinopathy, which were carried out from October 1987 to February 1989. The extent of central or peripheral traction and retinal detachment were found to have a major influence on the choice of intraocular tamponades. Different types of diabetes, renal failure, and the time interval since the last vitreous hemorrhage showed no influence on the choice of intraocular tamponades. Visual acuity was improved after vitrectomy in the group with silicone oil tamponade, as well as in the control group with BSS or gas tamponade. Patients receiving silicone oil had more advanced stages of proliferative diabetic retinopathy and therefore more complicated postsurgical courses. Silicone oil is more likely to be avoided in cases without retinal detachment, where the risk of further vitreous hemorrhage is felt to be low and in cases with complete panretinal photocoagulation. The present study supports the therapeutic value of complete panretinal photocoagulation for proliferative diabetic retinopathy--even in cases where the proliferative retinopathy progresses and a vitrectomy is needed. It is demonstrated that many patients requiring vitrectomy did not receive sufficient photocoagulation earlier. PMID- 2272572 TI - [Surgical iridectomy following acute angle-closure glaucoma. A retrospective study of 107 patients]. AB - In 69 of 107 patients with primary angle-closure glaucoma, it was possible to control intraocular pressure and visual fields by means of peripheral surgical iridectomy; in 17 of these patients topical glaucoma medication was required in addition. In 11 cases a second surgical operation other than iridectomy was necessary: 6 lensectomies for malignant glaucoma in 2 cases and lens subluxation or phacomorphic glaucoma in 4 and 5 filtering procedures. Among the 85 treated fellow eyes 68 were controlled by iridectomy alone and 17 eyes needed additional topical glaucoma medication. One case of persisting wound leakage from the corneo/scleral wound was the only complication observed in this study. The advantages and disadvantages of peripheral surgical iridectomy are compared with those of argon and neodymium: YAG iridotomies. Owing to the low rate of complications the authors apply the surgical approach as the routine technique for primary angleclosure glaucoma. PMID- 2272573 TI - [Para-papillary chorioretinal atrophy in eyes with shallow glaucomatous optic disk cupping]. AB - Parapapillary chorioretinal atrophy is present in some, but not all glaucomatous eyes. We examined whether eyes with shallow or with deep optic cupping showed more pronounced parapapillary atrophy. To this end, we analyzed 15 degree color stereo optic disc photographs of 141 eyes of 95 normal subjects and 211 eyes of 120 patients suffering from chronic open-angle glaucoma morphometrically. Optic cup depth was semiquantitatively estimated in a relative score ranging from 0 to 5. It increased significantly with increasing glaucoma damage indicated by smaller neuroretinal rim area, higher visual field loss, decreased retinal nerve fiber layer index and more advanced morphological glaucoma stage. Conversely, optic cup depth was inversely correlated with parapapillary atrophy. It decreased significantly with increasing glaucomatous parapapillary atrophy. When two subgroups of eyes with deep and eyes with shallow cups, were formed, matched for neuroretinal rim area, perimetric defects and retinal nerve fiber layer index, the parapapillary atrophy was found to be significantly more pronounced in the subgroup with shallow optic cups than in the subgroup with deep cupping. We conclude that there is a correlation between shallow optic disc cupping and pronounced parapapillary chorioretinal atrophy. This may indicate a common element in their pathogenesis. PMID- 2272574 TI - [Local and diffuse changes in the nerve fiber layer in glaucoma and vascular involvement of the optic papilla. Perimetry correlates]. AB - Alterations in the retinal nerve-fiber layer, as seen in red-free illumination, are early signs of glaucomatous damage. First, small localized defects are often overseen in routine static automated perimetry, as the earliest psychophysical correlation is only a slight, localized increase in short-term fluctuation. Larger, absolute nerve-fiber-bundle defects of glaucomatous or vascular origin lead to broad, arcuate visual field defects, known as Bjerrum scotomata. Diffuse atrophy of the retinal nerve-fiber layer can also be seen in glaucomatous eyes, but it is difficult to detect and can therefore easily be missed by the observer. Perimetric correlations in these cases are mostly identical Bjerrum scotomata, as seen in localized nerve-fiber bundle defects. However, it seems possible that a diffuse reduction in sensitivity can only be detected. If stable fixation is attained, a good, but nevertheless indirect correspondence between the visual field defect and nerve-fiber bundle defect can be obtained by simply superimposing the fundus image on the perimetric results. Fundus-controlled perimetry is a direct combination of these two investigative methods. The advantage of fundus-controlled permetry is a precise, point-to-point correspondence between the fundus image and perimetric results, which is impossible to achieve by projection perimetry. The scanning laser ophthalmoscope is the most suitable device for simultaneously imaging the fundus and conducting psychophysical testing. For static fundus-controlled perimetry we adapted the confocal scanning laser ophthalmoscope from Rodenstock by adding an infrared laser for fundus imaging. The HeNe laser is still used for background illumination, generation of stimuli, and fixation by computer-controlled acousto optic modulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272575 TI - [Diagnostic references in optic nerve diseases using retinal nerve fiber photography]. AB - Two patients with optic nerve disease are reported. The first patient was 20 years old and had suffered a closed head injury 1 year earlier. She presented with an incongruous right hemianopsia; retinal nerve fiber layer photography disclosed an infragenicular lesion and descending atrophy of the medial postchiasmal parts of the optic tract. The second patients was 24 years old. He had had depressed visual acuity in his right eye for 7 h before presentation. Perimetry showed a quadrant anopsia of the lower nasal field. The diagnosis made on the basis of fluorescein-angiography was recurrent retinochorioiditis with acute occlusion of an arterial branch. Retinal nerve fiber layer photography in this early stage showed a more pronounced nerve fiber pattern in the area normally supplied by the occluded artery, most probably caused by axoplasmic edema; along the course nerve fibers showed ascending atrophy in this circumscribed area. In both cases papillometry had given no evidence of any alteration in the area of the neuroretinal rim. In contrast to glaucomatous optic atrophy, localized disturbances of perfusion apparently cannot be detected by examination of the area of the neuroretinal rim of the optic nerve. In nonglaucomatous optic nerve diseases retinal nerve fiber layer photography is more informative. PMID- 2272576 TI - [Papilledema. Follow-up using laser scanning tomography]. AB - Normally, the elevation of optic disk swelling is measured by ophthalmoscopy. Laser scanning tomography (LST) permits three-dimensional analysis of distinct intraocular structures under in vivo conditions with high accuracy. We present a case of papillitis, in which the elevation could be determined as 550 microns, leading to a volume of 1.48 mm3, increasing to an elevation of 870 microns and a volume of 1.72 mm3 11 days later. Clinically, we found a swelling of about 1 D in the first examination, increasing to 2 D at the maximum. Six weeks later there was only a distinct temporal pallor to be seen, while the LST showed us an elevation of 190 microns (volume 0.22 mm3). PMID- 2272577 TI - [Endothelium protective effect of the high viscosity substances hyaluronic acid and methylcellulose in mechanical damage]. AB - We investigated the protective effect of the high-viscosity substances sodium hyaluronate (1%) and methylcellulose (2%) on corneal endothelium in the face of severe mechanical insult. An intraocular lens was drawn across the endothelium of porcine corneas with standardized conditions. We used different compression forces. Methylcellulose and sodium hyaluronate were used as lubricating substances in the experimental groups, while balanced salt solution (BSS PLUS) was used in the control group. In this study no significant protective effect of high-viscosity substances against strong direct mechanical damage was generally demonstrable. Only one group in which a moderately strong compression force was applied showed significantly less smaller endothelial cell loss when methylcellulose was used. The most important function of viscous substances is therefore to prevent a collapse of the anterior chamber and to prevent any contact of the intraocular lens or of instruments with the endothelium. Any mechanical contact with the endothelium means an irreversible endothelial cell loss. PMID- 2272578 TI - [Laser keratomileusis for correction of myopia]. AB - Laser keratomileusis with the excimer laser (193 nm) is a new method of refractive surgery. With this procedure a thin lenticule is ablated from the central cornea with submicron precision. The refraction changes achieved in 13 eyes ranged from 1.5 to 7.5 dpt. With this correction 92% of the treated eyes were within 1.0 dpt either way at 3 months after surgery, but after 6 months this proportion decreased to 77%. The best-corrected visual acuity recovers within 1 months to preoperative values. In all patients a slight subepithelial haze was detected with the slit-lamp in the early postoperative phase, but cleared within 4-6 months to a clinically non-significant level. PMID- 2272579 TI - [Serologic diagnosis and follow-up in patients with uveitis. Antibodies to virulence antigens of Yersinia enterocolitica]. AB - Sera from 72 patients with uveitis and sera from 93 healthy blood donors were analyzed by an immunoblot technique for antibodies to plasmid-encoded virulence associated antigens of Yersinia enterocolitica. In the group of patients with acute anterior uveitis (n = 16), antibodies of the classes IgA, IgG, IgM were significantly increased in comparison to the healthy blood donors. The presence of IgA antibodies is a sign of acute or persistent Yersinia infection. For the other forms of uveitis these antibodies were not identifiable in such a significant number of patients. After 2 years, clinical and serological investigations were carried out again in these patients. At the time of the second investigation, 25/72 (34.7%) of these patients showed intraocular inflammatory activity (group 1), but in 47/72 (65.3%) ophthalmological inflammation was no longer present (group 2). The serological investigation of group 1 and group 2 showed no significant difference in the antibody response to Y. enterocolitica. From these results we conclude that a persistent or acute Yersinia infection is a possible trigger for acute anterior uveitis. To investigate an infection with Yersinia enterocolitica, a method demonstrating antibodies to the plasmid encoded antigens of Y. enterocolitica must be employed, because the virulence and the persistence of infection can only be analyzed by this technique. PMID- 2272580 TI - [Early ocular symptoms in Wegener's granulomatosis]. AB - Wegener's granulomatosis is characterized by necrotizing granulomatous vasculitis that initially occurs in a localized form, disseminates in various degrees and particularly involves the respiratory tract and kidneys. Eye manifestations are common (40 to 60%). Both clinical and histopathological findings are described in eight patients with Wegener's granulomatosis. The initial ocular symptoms included conjunctivitis, episcleritis, scleritis, corneoscleral ulceration, uveitis and ocular proptosis. In one patient histological examination of the orbital tissue was consistent with limited Wegener's granulomatosis 6 years before generalized granulomatous vasculitis confirmed the underlying disease. As new diagnostic and therapeutic modalities (detection of antineutrophil cytoplasmatic autoantibodies and therapy with trimethoprim-sulfamethoxazole) exist, a knowledge of the ocular initial symptoms of Wegener's granulomatosis can have considerable significance. PMID- 2272581 TI - [The second, mucus-secreting system of the conjunctiva. Ultrastructural findings]. AB - The second mucus-secreting system (type II cells according to our classification) of the conjunctiva is important for moisturization of the ocular surface epithelia. Ultrastructurally, a merocrine and an apocrine type of secretion can be differentiated. The merocrine secretion (epithelial cells containing homogeneous or inhomogeneous osmiophilic granules) appears more or less in all conjunctival areas. The apocrine mode of secretion is only found in the multilayered cylinder epithelium of the fornix conjunctivae. On the whole, the type II cells with inhomogeneous, osmiophilic vesicles are the most common. In the apical area of these cells secretory vesicles either coalesce with the cell membrane or they are completely released to the cell surface. Within the human conjunctiva about 10% of the superficial epithelial cells have secretory functions. Their number slightly increases in the temporal areas of the conjunctiva and in persons under 20 years and over 60 years of age. These results were obtained by electron microscopical investigations of conjunctival biopsies from 48 persons without conjunctival diseases. PMID- 2272582 TI - [Functional results after surgery of congenital cataract]. AB - In this retrospective study, the functional results of a total of 14 children with congenital cataract have been analyzed. Four had unilateral and 10 cases bilateral cataract. All children were operated on before the age of 4 months and received a silicone permanent-wear contact lens a few days after the operation. At the time of surgery in all children with unilateral cataract we found additional pathology of the eye, such as microcornea or strabismus. The children with bilateral cataract had secondary eye disorders such as nystagmus and strabismus. After an average follow-up time of 4.5 years, the children with unilateral aphakia reached a visual acuity of 10/200 in the cases with bilateral aphakias an average visual acuity of 60/200 was obtained. In the future, improvement of the functional results can only be achieved when the diagnosis and therapy take place before secondary eye disorders develop such as nystagmus and strabismus. PMID- 2272583 TI - [Amblyopia: reading speed in comparison with visual acuity for gratings, single Landolt Cs and series Landolt Cs]. AB - In the treatment of amblyopia in preschool children, a means of predicting later reading ability would be helpful. This prediction might be possible using a test for visual acuity where the results correlate with reading ability in adult patients with amblyopia. We measured the following four parameters in 18 experienced readers with strabismic amblyopia: (1) time spent reading ten lines of a standard text in one of three magnifications, (2) visual acuity for gratings, (3) visual acuity for single Landolt Cs, and (4) visual acuity for crowded Landolt Cs (one Landolt C flanked by two full rings on each side each at a distance of 2.6 min of arc). The reading text was presented on paper at a distance of 40 cm; the subject had a choice of three magnifications. The acuity tests were generated by a computer on a VDU at 4.6 m. The relative impairment of the amblyopic eye was defined as the quotient between the performance of the amblyopic and the good eye. In addition, the difference between the times spent reading the ten lines with the amblyopic and with the good eye was calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272584 TI - [Results of Rauschfeld examinations with the Tubingen electronic campimeter. A comparison with current perimetry procedures]. AB - In a total of 121 patients scotomata, detected by white-noise campimetry, were presented graphically in a standardized manner. The intensity of brightness and strength of motion ("noise") perception within the scotoma, as well as the reliability of the patients' statements, were taken into consideration. The results of white-noise campimetry were compared with conventional raster perimetry using the Tubingen automatic perimeter. In each case the examiner was naive with respect to the result of the other method. In 77% of all comparisons, the correspondence between the results obtained with white-noise campimetry, on the one hand, and automatic perimetry on the other was sufficiently close, so that one method confirmed the other. However, when white-noise campimetry was used alone congenital visual field defects, long-standing retinal scotomata, and old suprageniculate lesions mostly could not be detected. When these defects were excluded from the analysis, the correspondence between the two methods increased to 85% (in the 89 remaining patients). Special applications of white-noise campimetry as a screening method or for the purpose of patient self-examination are discussed. Furthermore, it is suggested that this method could be used as a tolerance test for revealing expansion of the scotoma under short-term artificial elevation of the intraocular pressure. PMID- 2272585 TI - [Perception of the blind spot with Rauschfeld campimetry. An additional diagnostic criterion in papillary changes]. AB - In conventional test point perimetry the optic disc is detected as an absolute scotoma (blind spot). However, in white noise campimetry the blind spot usually cannot be perceived: the white noise is continuous over the whole field if presented to a normal eye. This is true not only for the blind spot but also for all scotomas caused by congenital damage to the retina or the visual pathway (e.g. colobomas). On the other hand, the blind spot is always perceived in white noise campimetry if acquired damage to the peri-cecal region is present. In such cases this method can give important information concerning the etiology of an enlarged blind spot detected with conventional test point perimetry. In addition during the follow-up of a papilledema, fading of the perception of the blind spot in the white-noise field indicates when the edema is resolved. Results of white noise campimetry in papilledema, glaucomatous atrophy of the optic disc and anterior ischemic optic neuropathy are presented and compared with findings of conventional test point perimentry. PMID- 2272586 TI - [Oculoplastic therapy in generalized nevus verrucosus]. AB - The clinical and histopathological picture of a 27-year-old patient with generalized nevus verrucosus is described. The oculoplastic treatment performed in this patient consisted in lid plasties, surgical excision, cauterization and cryotherapy. The different therapeutic techniques were applied over a period of 2 years. Nearly all papillomatous lesions were removed without impairing lid contour or lid function. PMID- 2272587 TI - [Bilateral dacryocystography using digital subtraction technic for kinetic evaluation of the lacrimal passage]. AB - For dacryocystography we used the following procedure: after bilateral intubation of either the inferior or superior canaliculi with two galactography tubes connected with an Y-adapter, aqueous contrast medium (Ultravist 370) was injected. The lacrimal pathways were then imaged with the digital subtraction technique (Siemens Polytron), as well as with conventional film. In cases of postsaccal stenosis, the relative delay of contrast medium passage--compared with the normal side--could be specified. A diverticulum of the canaliculus and a transitional cell carcinoma of the lacrimal sac could be demonstrated with both techniques. For the purpose of the post-operative follow-up after dacryocystorhinostomy, bilateral digital dacryocystography is particularly helpful because of the good documentation provided on pathway kinetics. However, digital subtraction dacryocystography cannot fully replace conventional dacryocystography. PMID- 2272588 TI - [Ophthalmologic complications in mitral valve prolapse]. AB - Usually, mitral valve prolapse is a benign condition, but there are some reports about ischemic cerebral or ocular insults. Among our patients with ischemic ophthalmic diseases we found seven with no risk factors other than mitral valve prolapse. The ages ranged from 18 to 61 years. Three patients suffered from monocular amaurosis fugax. Two patients showed a transient homonymous visual field defect. One patient had a vascular brain-stem lesion in the lower pons, causing a skew deviation. One patient showed typical anterior ischemic optic neuropathy. All but one patient (ischemic optic neuropathy) recovered completely. We recommend secondary prophylaxis with low-dose aspirin in cases where the symptoms persist longer than 24 h. PMID- 2272589 TI - [Is an implant always necessary after enucleation?]. AB - A retrospective study was performed on 114 patients who had received an intraorbital ball implant after removal of an eye: 44 had a primary implant inserted at the time of enucleation and 70 a secondary implant, inserted at a later date. We observed distinct advantages in the primary implantation group. Patients with a primary implant, an acrylic ball covered with sclera inserted within Tenon's capsule, had better cosmetic results and a lower complication rate and fewer needed any other therapeutic measures. Of the patients with primary implants 89% did not require further treatment, as against 51% with secondary implants. PMID- 2272590 TI - [Imaging of intraocular and orbital vessels using angiodynography]. AB - Color Doppler imaging (CDI) is a recent advance in ultrasonography. It allows simultaneous two-dimensional structural imaging and evaluation of blood-flow characteristics. The velocity information of the scan is extracted and added to the images as color information. A total of 20 normal eyes and 30 patients with intraocular tumors were examined with this technique. The central retinal artery, the posterior cliliary arteries, the opthalmic artery and the central retinal vein could be located in all patients. In the intraocular tumors blood flow was detected reliably. Spectrum analysis of the displayed vessels allows semiquantitative assessment of blood flow in these vessels. This new technique of color Doppler imaging offers a new modality to study ocular and orbital blood flow. PMID- 2272591 TI - [Anophthalmos. Sequela of an unusual birth injury]. AB - A child is reported who was born with complete absence of the right globe after instrumental delivery. The delivery was difficult and had been carried out by application of suction cup and forceps. The clinical examination at our hospital some days after the delivery suggested accidental enucleation during birth. In addition to anophthalmia, only minor laceration of the conjunctiva, a hematoma of the lids and a skin wound close to the right cheek were present, but no further orbital injuries. In earlier literature, similar injuries with luxation of the globe during delivery have been reported but they were usually associated with heavy periorbital injuries. PMID- 2272592 TI - [Predictors of the course of schizophrenia--a review of the literature]. AB - As the course of schizophrenia shows a large variability, a prognosis of outcome is extremely difficult. The search for valid predictors shows that there exist numerous predictors with variable predictive significance for distinct outcome criteria and also for different phases of the illness. The indications in the literature are accordingly variable or even inconsistent. The following statements seem us to be proved: A good premorbid social adjustment, a harmonious premorbid personality, and an acute onset of the illness predict a better course, whereas an insidious onset and a development of marked negative symptoms correspond to a poorer outcome. A combination of several factors improves the predictive significance. The importance of the following indicators remains questionable: Genetic loading, neuropathological findings, positive symptoms, and age at onset of the illness. Equally open are these questions: How are the various indicators interrelated and for what span of time have they a predictive power? Psychosocial indicators have more predictive significance than the so far known biological variables. Probably the difficulties in finding valid predictors are not only related to unsolved methodological problems, but above all to intrinsic characteristics of the illness itself. PMID- 2272593 TI - [Antipsychiatry and identity crisis in psychiatry]. AB - Whereas at the turn of the century in Germany antipsychiatry left intact the medical concept of disease and comprehension of the role of the physician and medical institutions, this sector was initially questioned vehemently in the conception of "psychotherapie institutionelle" in France and later in the reform efforts in Britain and North-America. This disclosure of the questionability of an argumentation in terms of pure exact science promoted by the tendencies of the theory of science (Frankfurt School) in the 1950s and 1960s encouraged these reform efforts and questioned the objectivism which had been dominant up to that time. However, for the clinical domain it also led to a profound crisis of legitimation and thus to a crisis of the self-conception of the physician, which is linked fundamentally to diagnosis, indication and responsibly justified medical intervention. It was especially difficult to react appropriately to the challenges of antipsychiatry for those psychiatrists who had clearly recognized the deficiencies or the nonfeasibility of an approach based exclusively on exact science as a source of legitimation for medical action. These psychiatrists had gone along with the subjectivistic trend change with the criticism of traditional associated with this, asymmetric, dyadic doctor-patient relationship. In this context, they had rejected objectivizing diagnostics and the apersonal disease model ("therapeutic community") in the hope that this would bring about humanization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272594 TI - [Iridoplegia-areflexia syndrome (Weill/Reys-Holmes-Adie), symptoms and etiology as persistent herpes simplex virus infection]. AB - Looking for additional symptoms and signs of the iridoplegia-areflexia-syndrome referable to its unknown etiology we have found spotlike trigeminal numbness, edema, and/or redness suggestive of herpetic origin and more often common signs of herpes simplex virus-infection (HSVI). Indeed the whole picture of the syndrome as we see and describe it, can be explained by typical features of the HSVI. These include persisting HSVI of only the distal sensible or vegetative neurones and recurrence of infection with further destruction of ganglia-cells. These criteria are also decisive whether symptoms and signs may belong to the syndrome or not. To prove the hypothesis of HSVI etiology through other means is a necessity but seems to be difficult. PMID- 2272596 TI - [Psychoneuroimmunology. A new bridge between the mind and the body]. PMID- 2272595 TI - [Diagnostic differentiation of dementia diseases by modern imaging procedures]. AB - We present a review on recent neuroimaging techniques, like x-ray computed tomography (XCT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission tomography (SPECT) in dementia and related diseases. Significant new findings have been obtained using techniques reflecting proton density, regional brain perfusion and brain metabolism. In dementia of the Alzheimer type, for example, temporoparietal and sometimes also frontal reductions in cerebral blood flow and metabolism are characteristic. The infarctions found in multi-infarct dementia are especially well visualized on T2 weighted MRI images. Pick's disease is characterized by brain atrophy and decrease of radiotracer activity in the frontal lobes. In huntington's chorea the metabolic rate on PET scan in the area of the caudate nuclei may be reduced even before signs and symptoms become apparent. Furthermore, neuroimaging provides us with fairly typical finding in Creutzfeld-Jakob's disease, alcoholic dementia, Wilson's disease, hydrocephalus, Parkinson's disease, progressive supranuclear ophthalmoplegia, Fahr's disease, and the olivopontocerebellar ataxias. Neuroimaging techniques, however, have always to be interpreted in conjunction with clinical findings, thus disclosing their full range of information. PMID- 2272597 TI - Prognosis of pancreatic endocrine function in chronic pancreatitis: significance of surgical treatment. AB - Of 100 cases of chronic pancreatitis, 20 received surgical treatment. The duration of illness before surgical treatment was less than 5 years in 75% of patients. Post-operatively, the persistent abdominal pain was relieved and serum pancreatic enzyme levels were normalized in all the patients except two who continued drinking alcohol. Exocrine and endocrine pancreatic function were unchanged or slightly improved post-operatively in most cases. In 9 of 10 patients who have been followed up post-operatively for over 4 years, pancreatic endocrine function has been maintained by diet control with no significant impairment of glucose tolerance. These results suggest that in patients with chronic pancreatitis surgical intervention is of greatest benefit in preservation of pancreatic functions when it is performed at an early stage in which these functions are relatively well maintained. PMID- 2272598 TI - [Skin surface lipids and sweat of hand in girl students who complained of impaired skin on the hand by using household detergents]. AB - A questionnaire was presented to female university students concerning the relationship between the use of household detergent and the occurrence of impaired hands. In addition, in order to determine whether there was any relationship between the amounts and qualities of skin surface film and the incidence of impairments of hands, the following experiment was undertaken. From among the 1,861 female university students, 28 girls between the ages of 21-22 were chosen; 14 of whom had complained of impaired skin of hands (impairment group) attributable to household detergent during the past one year and 14 who had not experienced such disorders, either of the hands or elsewhere (non impairment group) during the same period. The method of collecting skin surface lipids and sweat simultaneously is for the subjects to wear special gloves made of a given cotton fabric by the modified method of Straus & Pochi for a fixed of time. Then, the skin surface lipids and sweat were analyzed to determine the differences between the impairment group and the non-impairment group. The following results were obtained: 1) Of the 1,861 people surveyed, 496 or 26.7% of them stated that they had suffered from impaired skin due to the use of household detergents during the past one year. The most frequent site was the hands, including wrists, and the main symptom was dry skin. There were some seasonal changes in the occurrence of the impaired skin, with the highest occurrence in winter. There was a significant difference between the occurrence in winter, and that in spring, summer and autumn (p less than 0.01). 2) During the hot season, (average temperature 23-29 degrees C), the arithmetic averages and their standard deviation of the skin surface lipids of both the impairment group (N = 14) and the non-impairment group (N = 14) were 29.10 +/- 7.89 micrograms/cm2/8 hr and 45.98 +/- 23.29 micrograms/cm2/8 hr, respectively. In the cold season, (average temperature 5-13 degrees C), these become 31.95 +/- 16.69 micrograms/cm2/8 hr, and 53.45 +/- 24.16 micrograms/cm2/ 8 hr, respectively. In both these seasons, it was found that the amount of skin surface lipids of the impairment group was significantly less (hot season p less than 0.05, cold season p less than 0.01) than that of the non-impairment group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2272599 TI - [Monoamine contents and norepinephrine turnover in brain stem nuclei of young and adult spontaneously hypertensive and Wistar-Kyoto rats]. AB - To investigate the brain stem monoamine mechanism in the development and maintenance of hypertension of spontaneously hypertensive rats (SHR), we determined monoamine contents and norepinephrine turnover in discrete brain stem nuclei which are known to relate with cardiovascular control. Specific areas and brain stem nuclei were dissected from serial frozen slices of 300 microns thickness according to the atlas of Palkovits and Jacobowitz. The dissected tissues were homogenized, centrifuged and the supernatants were injected into high performance liquid chromatography with electrochemical detection (HPLC-ECD). Norepinephrine (NE), dopamine (DA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) contents were determined. NE turnover was also determined 2 hour after alpha-methyl-p-tyrosine administration (250 mg/kg, i.p.). In 4-week old SHR, the only significant change observed was decreased NE contents in the nucleus tractus solitarii (NTS). Such decreases in NE contents of the NTS were also found in 8- and 16-week old SHR. However, there were no differences in NE turnover in the NTS between SHR and WKY. Increased NE contents were found in the A1, A5, and nucleus reticularis gigantocellularis (RG) in the later stages (8 and 16 weeks) in SHR. Furthermore, increased NE turnover was seen in the RG of SHR at 16-week old, indicating increased neuronal activity. Dopamine, 5-HT and 5-HIAA showed no consistent changes between SHR and WKY. Increased NE levels were observed in later stages after development of hypertension, suggesting the increased NE in adult SHR may represent a central adaptive change secondary to the established hypertension. Since increased NE levels were consistently found in or around the regions which are known as vasomotor centers, we assume that these increased NE might serve to maintain hypertension or to inhibit a further increase in blood pressure. In contrast, the NE contents were decreased with constant turnover in NTS of SHR aged 4, 8, and 16 weeks. Constant turnover in NE could not compensate for reduced NE in NTS and may lead to a functional reduction or reduced noradrenergic activity. This defect in intrinsic noradrenergic neurons in NTS may trigger the development of genetic hypertension in SHR. In conclusion, the present results demonstrate that NE levels of SHR in the NTS were consistently decreased compared with those of WKY in all age groups. In later stages, increased NE levels were observed in A1, A5 and RG of SHR. These results indicate that brain stem monoamine system, especially noradrenergic neurons, contributes to the development and maintenance of hypertension in SHR. PMID- 2272600 TI - [Two cases of Turner's syndrome with spondyloepiphyseal dysplasia like bone appearance]. AB - We report two cases of mosaic karyotype (45XO/46XiXq) Turner's syndrome with unique bone appearance. The cases were 44 and 34 year-old women and latter was complicated by Hashimoto's thyroiditis (hypothyroidism). Following the systemic bone surveys, we found the patients showed not only osteoporotic bone change and short stature, but also spondyloepiphyseal dysplasia (SED) like bone appearance (thinness of vertebral bodies, irregularity of vertebral end-plates, shortness of femoral necks, Coxa valga, Coxa magna and hypoplasia of acetabula). Those findings can not be explained by degenerative bone changes like osteoporosis, rather are suggestive the sequelae of malgrowth of the bone system in Turner's syndrome. PMID- 2272601 TI - Mouse glomerular endothelial cells have an insulin receptor. AB - An insulin receptor was found on the surface of cloned mouse glomerular endothelial cells in vitro. Total specific binding was 2.5 +/- 0.3%/10(6) cells at 90 min and 22 degrees C. Analysis according to Scatchard resulted in a curvilinear plot, with a kd for the high and low affinity sites estimated at 1.41 x 10(-10) and 8.2 x 10(-8) respectively. Insulin binding decreased following 12 hour exposure to 50 ng/ml of insulin suggesting that down regulation of the receptor had occurred, an effect which was reversible. Covalent crosslinking of the receptor to 125I insulin revealed one band at Mr 125,000 by SDS-PAGE which disappeared following preincubation with excess unlabeled insulin. Insulin was also able to stimulate phosphorylation of the beta subunit. The characteristics of this insulin receptor appear very similar to that of endothelial cell types from other microvascular beds. PMID- 2272602 TI - Ketone body utilization for lipogenesis in the perfused liver of the obese Zucker rat. AB - The purpose of these studies was to determine if the utilization of ketone bodies as a carbon source for lipogenesis could account for the decreased ketone body production by livers of obese Zucker rats, as well as contribute to the enhanced rates of fatty acid synthesis observed in these animals. Ketone body production was decreased from 822 mumol/liver in the lean to 538 mumol/liver in the obese genotype (P less than 0.05). The incorporation of ketone bodies into fatty acids was significantly greater in the obese rat liver (lean, 1.95 mumol of ketone bodies/liver, versus obese, 35.22 mumol/liver; P less than 0.025). The relative contribution of this pathway to the overall rate of fatty acid synthesis was not affected by genotype and accounted for only 3 to 4% of the fatty acids synthesized. The incorporation of ketone bodies into digitonin precipitable sterols was similar in the two genotypes (lean, 4.5 mmol/liver, versus obese 4.7 mumol/liver; NS). This accounted for 9.2 and 6.3% of the total sterol synthesis in lean and obese rat livers, respectively. The total incorporation of ketone bodies into lipid was 7.5 mumols in the lean rat livers and 42.0 mumoles in the obese (P less than 0.025). The net increase was 35 mumoles incorporated, whereas the net decrease in ketogenesis was 284 mumoles. Thus, although ketone body carbon utilization for lipid synthesis was increased in the liver of the obese rats, this pathway could only account for a fraction of the genotypic difference in ketone body production and was of relatively minor importance as a source of carbon for hepatic fatty acid synthesis in both lean and obese rats. PMID- 2272603 TI - Growth hormone induced stimulation of the T4 to T3 conversion in fed and fasting dwarf goats. AB - Fed and food deprived (7 days) adult dwarf goats were injected intravenously with 75 micrograms/kg b. w. of ovine growth hormone (o-GH). Blood samples were collected from the jugular vein -2, -1 and 0 hr prior to and 30, 60, 90 and 120 min after injection and assayed for thyroxine (T4) and triiodothyronine (T3) concentrations. The 5'-monodeiodination (5'-D) activity was consequently determined in liver and kidney samples following slaughtering. Fasting alone increased plasma concentrations of T3 and T4, whereas injection of o-GH raised T3 additionally and more profoundly in food deprived animals compared to fed ones. A small increase in plasma T4 was also observed following o-GH injection, but only in starved goats. At the same time the hepatic, but not the kidney, 5'-D activity was stimulated in food deprived and GH injected animals. It is concluded that during prolonged fasting an increased peripheral T4 to T3 conversion is occurring contrary to the known decrease in T3 production during short periods of food deprivation. This increased conversion may be under the control of GH. PMID- 2272604 TI - Adjunctive use of tolazamide in newly-diagnosed diabetic children. AB - Recent data suggests that one of the major actions of sulfonylureas is to potentiate the anabolic cellular effects of insulin. This is the first study to examine the use of sulfonylureas as adjunctive therapy in newly-diagnosed type I diabetic children. A random, prospective, double blind study over 15 months, stratified by age at diagnosis, was conducted. The treatment group (n = 13) received daily oral weight-adjusted tolazamide whereas the control group (n = 11) received placebo. Monthly comparison of the HbA1 values between groups revealed no statistical difference; likewise, the fasting serum C-peptide values were not dissimilar. The mean daily insulin dose per kilogram, however, was less in the tolazamide group (P less than 0.001). The data suggests that the addition of tolazamide may not be of therapeutic benefit in newly diagnosed juvenile diabetics, although insulin requirements may be reduced. PMID- 2272605 TI - Apolipoprotein E phenotype frequency in type II diabetic patients with different forms of hyperlipoproteinemia. AB - Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia. PMID- 2272606 TI - Central actions of interleukin-8 in the rat are independent of prostaglandins. PMID- 2272607 TI - Growth hormone response to a bolus injection of 1-44 growth-hormone-releasing hormone in very short children with intrauterine onset of growth failure. AB - The release of growth hormone (GH) during the 120 min following a bolus venous injection of 1-44 GH-releasing hormone (GHRH) 2 micrograms/kg was studied in 52 prepubertal children aged 8.4 +/- 2.1 years, having a nonfamilial growth deficiency of prenatal onset (-3.26 +/- 1.13 SDS at birth, -3.22 +/- 0.88 SDS at the time of study) and a normal response to conventional GH stimulation tests. GH release reached a peak level of 96.1 +/- 60.2 microU/ml, being significantly higher than that found in 68 non-GH-deficient very short children whose growth failure had a postnatal onset, and not significantly correlated with the response to conventional tests. 26 of the 52 intrauterine growth retardation (IUGR) patients were re-tested with GHRH in similar conditions after 6-12 months of daily subcutaneous injections of GH and 2 days without. They reached at the second test a peak plasma GH level of 91.7 +/- 56.1 microU/ml, not different from their response to the first test. These data could be taken into consideration for long-term studies of the clinical effects of GH in IUGR children with persisting severe growth deficiency. PMID- 2272608 TI - Plasma active and inactive renin concentrations in children. AB - Plasma active and inactive renin concentrations (PARC and PIRC) were measured by immunoradiometric assay. Age-related changes in PARC, PIRC and the ratio of PARC/PIRC were studied in 78 normal children, age 1 month to 15 years. The effects of upright position for 15 min were also investigated in 7 postmenarcheal girls. PARC and PIRC in infants were significantly higher than in older children and their ratio of PARC/PIRC was significantly lower than in prepubertal children. During puberty, PARC, PIRC and their ratio were higher in premenarcheal girls than in postmenarcheal girls. In the upright position, PARC, PIRC and the ratio were increased significantly. These finding suggest that: (1) the production of inactive renin is increased but the activation of renin may be lowered in infants; (2) the activation of renin is affected by the menstrual cycle, and (3) the production and activation of renin are increased during short term standing. PMID- 2272609 TI - Production of interleukin-1-alpha and interleukin-2 by mononuclear cells in healthy adults in relation to different experimental conditions and to the presence of growth hormone. AB - Several reports support the view that the growth hormone (GH) possesses a number of important immunomodulatory properties. This study was undertaken to determine in vitro the role of the GH on interleukin (IL) production. Cultures of blood peripheral lymphocytes obtained from human normal adults were performed in RPMI medium in the presence or absence of phytohemagglutinin (PHA), heated normal serum (NHS) 1% and GH 12.5-500 microgram/l. After incubation from 15 h to 4 days at 37 degrees C in a humidified atmosphere containing 5% CO2, cells were discarded and the supernatants were tested for their contents of IL-1 alpha and IL-2 measured using the Amersham radioimmunoassay system. The results of these in vitro experiments show that: (1) the bulk cultures from peripheral lymphocytes are suitable to study the IL-1 and IL-2 production; (2) in optimal conditions for IL production (incubation during 48 h in the presence of PHA and NHS) no effect of GH was observed on IL production; (3) in the absence of PHA GH acts at physiological doses (less than 100 ng/ml) by increasing the IL production. This effect of GH was optimized with a short time of incubation (16 h) and in the simplest conditions of cultures, that is to say in the absence of serum and of PHA: thus in the presence of GH 100 ng/ml the IL-1 production increases from 0.53 to 3.86 fmol (tubes) and IL-2 increases from 0.18 to 3.22 fmol (tubes). These differences are significant (p less than 0.001). We conclude that GH acts in vitro on mononuclear cells to induce IL production. PMID- 2272610 TI - Circannual rhythm of plasma thyrotropin in middle-aged and old euthyroid subjects. AB - The circannual rhythm of plasma thyrotropin (TSH) was evaluated in 8,310 euthyroid, serially independent, young, middle-aged and old men and women. A statistically significant circannual rhythm of plasma TSH was validated, by the mean group-cosinor method, in the middle-aged and old men and women (p less than 0.05), with acrophase in December, whereas the young subjects did not show any rhythm. No significant correlation was found between TSH plasma levels and free thyroxine (fT4) or ambient temperature in any group. Moreover, plasma fT4 did not show seasonal variations. PMID- 2272611 TI - Human pancreatic polypeptide responsiveness to insulin-induced hypoglycemia in anorexia nervosa. AB - Patients with anorexia nervosa occasionally suffer from hypoglycemic comas. We investigated the role of human pancreatic polypeptide (HPP) in insulin-induced hypoglycemia (0.1 U/kg of regular insulin). Ten female patients with anorexia nervosa (20.7 +/- 2.0 years, mean +/- SEM; 34.9 +/- 1.7 kg, mean +/- SEM) and 8 age-matched female controls (20.9 +/- 0.6 years, 51.5 +/- 0.8 kg) were tested. In the patients with anorexia nervosa, testing was performed before and after the restoration of body weight (45.0 +/- 0.8 kg). There was no significant difference in glucose nadir between patients with anorexia nervosa and the control subjects. However, glucose recovery from nadir was delayed in patients with anorexia nervosa. In anorexia nervosa patients, the plasma pancreatic glucagon responses to insulin-induced hypoglycemia did not differ from those of the controls. Results also showed, however, that HPP responses to insulin-induced hypoglycemia were significantly higher in patients with anorexia nervosa than in controls (p less than 0.01). The increased HPP responses were still present after the restoration of body weight in anorexia nervosa patients. A complete body weight recovery or a longer period of time may be required to normalize the HPP response to insulin-induced hypoglycemia in patients with anorexia nervosa, after the restoration of body weight. PMID- 2272612 TI - Modeling glucose metabolism in man: theory and practice. AB - Quantitative assessment of whole-body and regional glucose metabolism from in vivo kinetic data requires a model of the system, i.e. specific assumptions about the structure and functioning of the system. We discuss here models which allow the measurement and understanding of the kinetics of glucose metabolism in vivo in man and of the effect of insulin upon them. Discussed models include: a whole body description of glucose distribution and metabolism to quantitate insulin effect; a model to measure in vivo glucose transport in the forearm; physiological models to assess glucose kinetics in the non-steady state; the insulin and C-peptide IVGTT minimal models to assess beta-cell function; the labelled IVGTT minimal models to assess insulin sensitivity and hepatic production. Emphasis is on models of the compartmental type and on the crucial role of modeling methodology. Aspects of improved experiment design are also discussed. PMID- 2272613 TI - A model-based system for the individual prediction of metabolic responses to improve therapy in type I diabetes. AB - Despite recent achievements such as home glucose monitoring and intensified injection regimens or insulin pumps, the metabolic care in diabetic patients is still mostly insufficient. One approach of further improving the management is the application of computer-aided procedures to estimate individually the optimal regimes. To accomplish this, a model-based strategy was developed which permits the prospective assessment of the metabolic outcome. This strategy comprises the following components: (1) a validated model of the physiological glucose-insulin regulatory system; (2) a procedure for identifying the metabolic situation of a given patient in terms of the model parameters; (3) methods of estimating the pharmacokinetics of insulin and its effect on glycemia, the absorption profiles of ingested glucose equivalents, and the effect of exercise as expressed in equivalents of insulin action; (4) computer procedures of prospective simulation of glycemic profiles around the day under the influence of selected or proposed therapeutic regimes. The entire method has been validated in C-peptide negative type I diabetic patients by comparing experimental results with theoretical predictions from model-based simulations over up to one year. This model-based simulation may be applied by ambulatory patients together with their physicians as a decision-support system in selecting appropriate individually suited regimes. PMID- 2272614 TI - Data management and expert systems for outpatient diabetes care--16 years experience with diabeta. AB - The continuing development and implementation of a computer-based diabetes register and management system are described. For 15 years the system has been used as a readily accessible source of clinical data, for letter generation, for prompting screening procedures and for clinical audit and research. Later developments include the incorporation of specialist "intelligence" for advising management of individual patients. This is intended for use by non-specialists to enable their greater participation in diabetes care. It is currently undergoing preliminary evaluation with a view to conducting clinical trials both in Hospital and in General Practice. PMID- 2272615 TI - Analysis and processing of data in a hospital-based diabetes management system. AB - Both short-term care (blood glucose monitoring) and long-term care (clinical examinations) of diabetes generate an ample amount of data for each patient. Health care in hospitals has to provide services with respect to both demands. The quality of control depends on obtaining the right finding at the right time and taking the individually adequate measures. These repetitive activities follow to a certain extent standardized algorithms and computer-programs are able to support demands like this; however, up to now no attempts have been made to provide useful tools for this environment. DIALIN is a data-bank especially designed for the use in hospitals or outclinics and Camit is a diabetes management system for advanced evaluation of long-term blood glucose monitoring data. The expert-system DIACONS up to now determines diabetes type and adequate initial therapy from data of patients' history alone; it operates on the DIALIN databank via SQL. DIALIN has proven to be a useful tool for data-processing in hospitals. Camit was well accepted by patients in a feasibility study. DIACONS has been tested with 83 diabetic patients to provide the correct diabetes-type and the proper initial regimen with a precision of 96% compared to the correspondence between two independent experts. The combination of all three systems is a step towards the Munich Medical Information system MAMIS. PMID- 2272616 TI - Computer assisted insulin dosage adjustment--perspectives for diabetes control. AB - Pocket computers provide the physician's (expert's) advice at home and by that may increase the number of self-adapting diabetics and alleviate documentation and evaluation of therapy data. By a more complex quantitative approach metabolic control may be improved beyond the range which is attained by optimal intensified education, as clinical trials showed. By their reproducible measures a learning process seems to be induced in the patients. Risks like hyperinsulinisation may be overcome by watch dog functions and suitable algorithms. In addition to these patient-oriented functions the automatic data acquisition may be used for secondary PC-assisted data interpretation and more complex advice at the physicians office. For compliance reasons the system concept has to be user friendly considering size, easy handling and compensating for the loss of a written log book by adequate display. PMID- 2272617 TI - Diabetes expert systems: planning for long term use. AB - Expert systems may play an important role in the future in assisting diabetics to control their disease. However the data available suggest that expert systems are difficult to build and more difficult to maintain over a long period. An examination of the problems in maintaining one expert system, GARVAN-ES1, suggests that the problems arise because experts never report on how they reach a decision, rather they justify why the decision is correct. These justifications vary markedly with the context in which they are required, but in context they are accurate and adequate; the difficulties arise in taking them out of context. It is suggested that expert system building techniques must be able to capture knowledge in context and tools must be available to flexibly change the context in which an expert system knowledge base is examined. Two implementations of such strategies, "ripple down rules" and a "knowledge dictionary", are outlined. PMID- 2272618 TI - Four years experience with the microcomputer system "Diacon" in the treatment and education of diabetes. AB - The use of a user-friendly microcomputer system "DIACON" which stores, analyses and displays blood glucose, details of the nutrition intake, insulin dose and other details relevant to diabetes management is described. This system tested for over four years in more than 100 diabetic patients has proven to be a useful educational and therapeutic tool. PMID- 2272619 TI - Six generations of the insulin dosage computer: a new clinical device for diabetes self-management through specialized centres. AB - Modern technology and dedicated micro-processors in particular, are revolutionizing the treatment of diabetes. Through specialized centres and a select group of new medical experts, conventional diabetes management is gradually being replaced by a system of technology assisted self-care. The present paper outlines the characteristics of six consecutive generations of a new device called an insulin dosage computer. It facilitates self-care by calculating insulin dosages each day at each meal based on glucose measurements made by the patients themselves. The device was initially developed in 1982 and is now extended to over 1200 patients each of whom has acquired expert skills for self-management and thereby achieved improved metabolic control with freedom both from hypoglycemia and from the psychological dependencies usually accompanying this disorder. PMID- 2272620 TI - Implantable insulin pumps: a major piece of computerized diabetes therapy. AB - There is a significant need for revised, safe and more effective insulin delivery methods than subcutaneous insulin therapy, including CSII, in the treatment of type 1 diabetes. The aim of the review is to describe the current status, issues and prospects of insulin therapy with implantable insulin pumps. The International Registry of Human Implantation reports that, as of May 1988, 249 pumps have been implanted, using the intravenous or intraperitoneal route for insulin infusion. The data suggest a reasonable safety of the method, no pump run away having been reported and only one patient having died of severe hypoglycemia possibly related to the pump. The more recent European (POINT) and U.S. (PIMS) trials with programmable pumps have confirmed the safety and suggested a better efficacy of the method over subcutaneous insulin administration. They also have pointed out that in order to represent an acceptable alternative to existing methods, implantable pumps still have to a) cope with or increase catheter longevity, presently of 2-3 years only, namely by improving catheter biocompatibility and b) clearly prove its superiority over subcutaneous methods at controlling diabetes, using large-scale, randomized, prospective controlled studies. PMID- 2272621 TI - The glucose sensor: the missing link in diabetes therapy. AB - This review considers the present state of the implantable glucose sensor from the point of view of technical models available today. Chemical analysis behind the practical experiences under both in vitro and in vivo conditions are described (Abel, Fischer, Brunstein and Ertle 1988; Bruckel, Kerner, Zier, Steinbach and Pfeiffer 1988a; Bruckel, Kerner, Zier, Steinbach and Pfeiffer 1988b; Steinbach, Kerner, Zier, Dolderer and Pfeiffer 1987). Amperometric enzymatic glucose sensors are used by the majority of laboratories, providing satisfactory results of glucose determinan in solution and in the laboratory. Up to 4 days of reliable values were recorded by measuring glucose in vivo, in practical terms, in the subcutaneous tissue in animals. However, also in this first period of foreign-body reactions, enough encapsulation obviously occurs to neutralize the majority of the sensors implanted. In first experiments in humans, the results are even worse. Generally, decreasing activity was observed in less than 24 h. Therefore, continuous blood glucose monitoring by portable glucose sensors used the same principle in a flow-through chamber; the sensor of our own make was employed in a number of clinical conditions. When one of the available insulin pumps effecting continuous subcutaneous insulin infusions was connected, the algorithms worked out for the big AEP under bedside conditions were also of use in a slightly modified fashion for the subcutaneous insulin application. Renouncing the computer-mediated automated regulation of the insulin delivery is possible when the patient is constantly reading his blood glucose values and operates the insulin infusion pulses in association with meals. Continuous glucose monitoring by portable instruments is the only and irreplaceable prerequisite for unprejudiced evaluation of the various strategies for substitution of the insulin deficiency in any form of diabetes. PMID- 2272622 TI - Choice and use of tracers. AB - The isotope dilution method has been widely employed to measure glucose turnover in man. The validity of this technique depends upon several assumptions. First, it is assumed that the selected model of glucose kinetics is valid. Under nonsteady state conditions this has recently been challenged for the most commonly used single compartment model. Secondly, it is assumed that the isotope is metabolized in the same manner as unlabeled glucose. If the isotope loses its label when subject to a substrate cycle (for example, [2-3H]glucose in glucose to glucose 6-phosphate cycling), an overestimate of glucose disposal will result. In contrast, if isotope that has been cleared (for example [6-3H]glucose in hepatic glucogen) is recycled into the systemic circulation, an underestimation of glucose turnover will result. Thirdly, it is assumed that measurement of specific activity is accurate. It has recently been shown that many commercially available tritiated (but not 14C) isotopes contain radioactive nonglucose contaminants which have a slower clearance rate than glucose under conditions of high glucose turnover. This can result in overestimates of specific activity and underestimates of glucose appearance, leading to calculated negative hepatic glucose release. While this problem may be avoided with purified tritiated glucose tracers, a similar problem with stable isotopes of glucose remains to be determined. In summary, the choice of glucose isotope should reflect the probability of substrate cycling and isotope cycling in the experiment in question. Care should be taken to ensure purified isotopes are selected and that the model of glucose kinetics used is valid during the conditions to be studied. PMID- 2272623 TI - Estimation of glucose kinetics following an oral glucose load. Methods and applications. AB - The measurement of glucose kinetics using glucose tracers is well established and validated. Several models of the glucose system have been proposed. In this review, two of these models will be described and their application to the measurement of glucose kinetics during an oral glucose tolerance test discussed. Examples of the applications of this method will be given illustrating the type of questions that can be addressed using this approach. PMID- 2272624 TI - Tracer studies of liver metabolism. AB - We have attempted to show a number of uses of tracers both as enhancing the information obtained in arterio-venous difference studies and in allowing the collection of data on hepatic metabolism--glucose production, glycogen formation, etc. in a noninvasive fashion. We have demonstrated, using these methods, that (1) The fractional extraction of glucose by the liver during glucose loading is about 5%; (2) This extraction can lead to significant hepatic glucose uptake (25 g after 100 g glucose load); (3) Only some of this glucose (10 g) is taken up directly into glycogen; (4) The remainder of the glycogen formed following a glucose load (15 g) is synthesized by gluconeogenetic pathways; (5) This gluconeogenesis takes place primarily from lactate which is taken up avidly by the liver--50-60% extracted; (6) This lactate arises from the gut (40%) and from the liver itself (at least 10%) with the remainder from other peripheral obligate lactate producing tissue; (7) It was also shown that the amount and pathways of hepatic glycogen production after oral and intravenous glucose loading is very similar and that the major effects on glucose tolerance take place in peripheral tissues such as the forearm. PMID- 2272625 TI - Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues. AB - The ability to study in vivo insulin action in specific muscle types and other individual tissues has been considerably enhanced following adaptation of the euglycemic clamp technique to the rat. The importance of this model derives particularly from its combination with administration of 3H-2-deoxyglucose and 14C-glucose. Analysis of the metabolic fate of these tracers at the conclusion of the clamp enables an assessment to be made of insulin action at both the whole body and the individual tissue level, the latter by estimating a tissue-specific glucose metabolic rate (from 3H-2-deoxyglucose phosphorylation). Information on stored vs utilised glucose can be obtained by simultaneously estimating 14C glucose incorporation into glycogen and/or lipids. This review briefly considers the basis of the technique and its recent application. It has been used to demonstrate in the rat that in vivo insulin sensitivity differs widely among insulin target tissues, such as adipose tissue, red and white skeletal muscle, and cardiac muscle. The technique has provided a means to study how factors such as diet, exercise, pregnancy, stress hormones and pharmacological agents modify in vivo insulin action in muscle and other tissues, to compare insulin and exercise as stimuli to muscle glucose uptake, and to examine factors which might be important in the aetiology of muscle insulin resistance. These new tracer techniques for in vivo use with the glucose clamp have narrowed the gap that exists between established whole body and cellular in vitro approaches to the study of insulin action and glucose metabolism. PMID- 2272626 TI - The role of the transcapillary insulin transport in the efficiency of insulin action: studies with glucose clamps and the minimal model. AB - Insulin action to augment glucose utilization (Rd) and suppress endogenous glucose production is not directly determined by changing plasma insulin, but rather by that insulin which traverses the capillary endothelial boundary to enter the interstitial space bathing insulin-sensitive cells. We have examined the importance of transcapillary insulin transport to the efficiency of insulin action by sampling insulin in thoracic duct lymph, believed to represent interstitial fluid, during euglycemic glucose clamps or intravenous glucose tolerance tests (IVGTTs) in conscious dogs. During clamps (insulin infusion: 0.6 mU/min per kg), we observed a 3:2 gradient between plasma and lymph insulin both at basal and at hyperinsulinemic steady state, which was reestablished after termination of infusion. No such gradient was observed for inulin, a non metabolizable diffusionary marker infused along with insulin. Furthermore, lymph insulin was proportional to Rd during clamps, and these two independently measured variables were strongly correlated (r = 0.96). These results indicate that transcapillary insulin transport is rate-limiting for insulin action during clamps. Compartmental analysis of insulin and inulin data was consistent with receptor-mediated transport of insulin across capillary endothelium from plasma to interstitium. Glucose tolerance tests were subjected to minimal model analysis, which yields the insulin sensitivity index (SI) and X(t), the rate of net glucose disposition during the intravenous test. Preliminary data reveal a striking similarity between the time courses of X and measured lymph insulin during IVGTTs, evidence that interstitial insulin is virtually at equilibrium with the rate of glucose uptake. Thus, even in the non-steady state, transendothelial insulin transport is the rate determining step for insulin action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272627 TI - Application of minimal models to measuring insulin sensitivity. AB - Bergman's minimal model of glucose dynamics was used to analyse intravenous glucose tolerance tests in non-diabetic and non-insulin dependent diabetic subjects (NIDDM). This analytical approach yielded an index of insulin sensitivity in 63% of the non-diabetic and 15% of NIDDM subjects. When the model was constrained to search for the most likely parameter solutions, all the non diabetic and 96% of the diabetic plasma insulin-glucose curves could be solved. A comparison of the insulin sensitivity index derived from this constrained minimal model against the metabolic clearance rate of glucose during a hyperinsulinaemic clamp carried out on the same subjects showed a correlation of 0.84 (P less than 0.01, N = 12 normal subjects) and 0.65 (P less than 0.001, N = 21 NIDDM patients). We conclude that this modification of the minimal model may improve the number of intravenous glucose tolerance tests capable of systematic analysis in NIDDM subjects, giving a measure of insulin sensitivity that correlates with more established measures of this parameter. PMID- 2272629 TI - Application of structural model of glucose-insulin relations to assess beta-cell function and insulin sensitivity. AB - A structural mathematical model of glucose-insulin relationships based on known quantitative responses of the major organs involved with glucose metabolism has been computed. Different degrees of beta-cell function and insulin sensitivity can be included, and the effect of their interaction assessed (i) in a steady state, basal homeostasis after an overnight fast and (ii) in response to a glucose infusion. By comparing a patient's basal plasma glucose and insulin (or C peptide) concentrations with the predictions of a basal homeostatic model, the degree of impairment of beta-cell function and insulin sensitivity can be assessed. Similarly, the plasma glucose and insulin (or C-peptide) concentrations after a continuous glucose infusion can also be compared with predictions from the model to estimate beta-cell function and insulin sensitivity. These assessments of pathophysiology can be applied to data from individual patients or to patient populations. PMID- 2272628 TI - Practical application of methods for in vivo assessment of insulin secretion and action. AB - In vivo measurement of insulin sensitivity can be made using the glucose clamp technique or the intravenous glucose tolerance test (IVGTT) with minimal model analysis. The glucose clamp provides a direct, readily understandable measure of insulin action but is more demanding for investigators and subjects. Assessment of insulin secretion must be made by a separate test. The IVGTT is easier to perform but the data are more difficult to analyse and the value for insulin sensitivity is a derived rather than direct measure. As well as insulin sensitivity, glucose mediated glucose disposal and insulin secretion are measured by the IVGTT. In fact the IVGTT technique relies on adequate endogenous insulin secretion whereas the glucose clamp does not. The choice between these two techniques depends on the study to be performed and the available laboratory facilities. PMID- 2272630 TI - Assessment of insulin needs in insulin-dependent diabetics and healthy volunteers under fasting conditions. AB - It is known from clinical observations, theoretical investigations as well as from data patients with intensified insulin therapy and wearers of insulin pumps that the body also requires insulin under fasting conditions. Therapeutic studies as well as the investigations carried out using the artificial pancreas indicate that just under half of the daily insulin requirement is not meal-related, and the other half is dependent on food. The question arose as to whether there are any differences in the basal insulin requirement depending on the time of day and whether differences can be detected between type I diabetics and healthy reference subjects. The results show that analogous changes occur in the early hours of the morning in type I diabetics and healthy normal subjects: these correspond to the clinical familiar dawn phenomenon. The different courses of blood glucose and insulin requirement as measured on the basis of the release of insulin by the Biostator as well as the insulin secretion profile in healthy normal volunteers under fasting conditions do not show any further differences which depend on the time of day. PMID- 2272631 TI - Meal-related insulin requirements. AB - Postprandial glycemia correlates with meal size in insulin dependent diabetic and nondiabetic persons. Decline in meal tolerance as the day progresses noted in nondiabetics does not occur in IDDM. Meal size correlates with insulin secretion in nondiabetics and amounts of insulin infused by an artificial endocrine pancreas to IDDM. There is no diurnal change in insulin secretion in nondiabetics or insulin infusion into IDDM but not amounts of insulin secretions by nondiabetics. Sequence of meal ingestion influenced amounts of insulin infused into IDDM. It is unclear to what extent variation in carbohydrate contribution or composition affect postprandial events. More precise quantitative measures of meal-related glucose behavior such as mean indices of meal excursions may be useful. CSII used in IDDM has been shown to normalize postprandial endogenous glucose production. PMID- 2272632 TI - Exercise and insulin requirements. AB - In order to facilitate the management of sports and work for insulin injecting diabetic patients we analyzed 6 different situations: 1) In the morning before injecting insulin stepwise increasing bicycle ergometry until exhaustion with a duration of less than one half hour may be performed without previous reduction of insulin or additional oral carbohydrates. Maximal work load can thus be determined with ECG monitoring. After insulin injection we advise our patients to estimate their reaction by calculating with exercise units. One exercise unit equals 20 minutes of half maximal exercise or one hour of 30% maximal exercise. 2) Performing one exercise unit the diabetic will have to anticipate a blood glucose reduction of -60 mg/dl. In order to maintain normal blood glucose levels he will have to reduce the regular insulin bolus 3) in the morning by -3,3 IU or 4) by -1.7 IU in the evening or he should 5) take +12 g of oral glucose (quickly absorbable carbohydrates). 6) A reduction of basal rate (CSII) or NPH insulin (ICT) is not advisable for exercise up to 3 hours. On the basis of these mean values every diabetic patient has to monitor blood glucose during exercise and adapt the measures to his individual reactions. PMID- 2272633 TI - Impact of activated glucose counterregulation on insulin requirements in insulin dependent diabetes mellitus. AB - The glucose counterregulatory system is one of the most important homeostatic systems in physiology, since it normally prevents hypoglycaemia or, should it occur for any reason such as insulin administration, limits the severity of hypoglycaemia and ultimately may restore normoglycaemia. In normal nondiabetic subjects, activation of counterregulation does not result in overt hyperglycaemia in the post-absorptive state, because the pancreatic beta-cell increases insulin secretion. On the contrary, in subjects with insulin-dependent diabetes mellitus (IDDM) whose pancreatic B-cell cannot respond to an increase in plasma glucose, activated counterregulation may easily result in overt hyperglycaemia. There are two different circumstances under which counterregulation may contribute to excessive hyperglycaemia in IDDM, namely nonhypoglycaemic nocturnal activation of counterregulation (dawn phenomenon), and hypoglycaemic activation of counterregulation (Somogyi phenomenon). The dawn phenomenon is an increase in insulin requirements which occurs between 04.00 and 08.00 h in the absence of preceding hypoglycaemia and concomitant hypoinsulinemia. It is caused by a decrease in hepatic and extrahepatic sensitivity to insulin induced by the nocturnal secretion of growth hormone. The dawn phenomenon may contribute importantly to fasting hyperglycaemia in IDDM, because usually plasma insulin concentration following the pre-supper insulin injection decreases after 04.00 h, i.e. a time at which plasma insulin concentration should instead increase to maintain normoglycaemia. The Somogyi phenomenon is best defined as hyperglycaemia following hypoglycaemia and is caused by the insulin resistance induced by hypoglycaemic-activation of counterregulation. Although insulin resistance following hypoglycaemia is a constant event in IDDM, post-hypoglycaemic hyperglycaemia is not the rule. For example, if the responses of counterregulatory hormones to nocturnal hypoglycaemia are blunted, or plasma insulin concentration following hypoglycaemia is inappropriately high, post hypoglycaemic insulin resistance is not powerful enough to result in overt hyperglycaemia in the fasting state. However, post-breakfast plasma glucose may be exaggerately elevated following nocturnal hypoglycaemia even in the case that fasting plasma glucose is only modestly increased. It is important to prevent nocturnal hypoglycaemia, not only to protect brain function, but also to prevent insulin resistance which may easily result in exaggerated hyperglycaemia and initiate the vicious circle "hypoglycaemia-hyperglycaemia-increase in insulin dose-risk for subsequent hypoglycaemia", and so on. PMID- 2272634 TI - Computers and diabetes therapy: key variables and quality of data for clinical decision-making. AB - Approaches to clinical decision-making in diabetes have undergone a revolution over the past decade. Since the introduction of reflectance meters and subsequently the addition of a micro chip to store glucose data, clinical decision-making by both the professional and person with diabetes has significantly changed. The memory-based reflectance meter made it possible to collect, aggregate and interpret self-monitored blood glucose values at a level of reliability and accuracy heretofore impossible to obtain. With the ability to collect self-monitored blood glucose values and transmit these data to micro computers has come the development of different approaches to the interpretation of these data. Innovations, such as the Ambulatory Glucose Profile and the Modal Day permit the expression of blood glucose values as dynamic entities. Using this means of representation, blood glucose over time can be thought of as a measure of change having such properties as variability and oscillation. By viewing blood glucose from this innovative perspective it may be possible to reexamine the relationship between insulin dose and glucose level and thereby improve clinical decision-making. PMID- 2272635 TI - Working nurse 101: first job. PMID- 2272636 TI - An unscientific guide to managing stress. PMID- 2272637 TI - Finding the right job. PMID- 2272638 TI - A practical guide to interviewing. PMID- 2272639 TI - Directory of nursing review books/review courses for NCLEX. PMID- 2272640 TI - Strategies for NCLEX-RN preparation. PMID- 2272641 TI - Non-activated rat neutrophils kill syngeneic colon tumor cells by the release of a low molecular weight factor. AB - The mechanisms of cancer cell destruction by unelicited peripheral blood neutrophils has never been reported in a syngeneic model. We demonstrated that in vitro, unelicited polymorphonuclear neutrophils isolated from rat blood were toxic against syngeneic colon cancer cells. The tumor cell lysis was not due to oxygen metabolites released by PMNs, but was due to a cytolytic factor. This factor was spontaneously secreted by PMNs, was heat-stable and had a low molecular weight (less than 10 kD). Its partial inhibition by chymotrypsin and/or chymotrypsin-like proteases suggested a peptidic structure of this factor. PMID- 2272642 TI - Latent inhibition of granulocyte function by cyclosporine A. AB - According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages. PMID- 2272643 TI - The effects of Peyer's patches inactivation in the rat on the development of antibody-forming cells to intestinal antigen. AB - The effects of Peyer's patch (PP) inactivation on local and systemic immune response in rats was investigated. A cauterization method has been developed to inactivate PP. Animals were primed intraperitoneally or intragastrically with trinitrophenyl-keyhole limpet haemocyanin (TNP-KLH) one day before cauterization, and were challenged intraintestinally two weeks later. The secondary immune response in the spleen, mesenteric lymph node (MLN) and intestinal villi was studied by immunohistochemistry. Histological observations on PP after inactivation showed that most T cells in the interfollicular area had disappeared, as had B cells in the follicle. T cells repopulated PP much slower than B cells. Complete recovery of PP occurred no earlier than 2 weeks after inactivation. The immunization experiments revealed higher numbers of anti-TNP antibody-forming cells (anti-TNP AFC) of IgM, IgG and IgA isotypes in the spleen of the PP-inactivated animals than in the controls. Very few anti-TNP AFC were found locally in the lamina propria of the intestinal villi or in the MLN in both groups. It is suggested that PP play a role in the regulation of systemic immune responses against intestinally-administered thymus-dependent antigen. Moreover, inactivation of PP could alter the antigen uptake by gut epithelium and the local antigen processing. As a result, an increased amount of antigen could reach the spleen eliciting a higher immune response. PMID- 2272644 TI - Detection of mutagenicity in cervico-vaginal secretions--a plausible risk factor for cervical cancer. AB - The cervico-vaginal secretions from 51 women with various grades of dysplastic lesions of uterine cervix were assessed for mutagenic potential by Ames test using histidine deficient mutant strain of Salmonella typhimurium TA-98: with S-9 mix. Twenty three per cent of samples from women with cervical dysplasia were found significantly positive (P less than 0.001) for mutagenic activity compared to 3% positive from control. The frequency of mutagenic secretions detected were almost uniform, irrespective of the severity of cervical lesions. None of cervico vaginal secretions, positive for mutagenicity could revert the tester strain when tested in absence of S-9 mix (liver microsomal enzymes). This indicates that mutagens in cervico-vaginal secretions are effective only when activated enzymatically. PMID- 2272645 TI - Effect of calcium channel blockers on experimentally induced seizures in rats. AB - Chemically different classes of calcium channel blockers were examined in rats for their effects on behavior, tolerability and protection against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures. In MES test at doses (mg/kg, ip) that were devoid of side effects, felodipine, 50, afforded 100% protection, while nimodipine, 5; pimozide, 10; and thioridazine, 25, showed 50 to 66% protection. Nifedipine, 10, and diltiazem, 50, showed 30 and 66% protection respectively, but were associated with side effects. Verapamil and loperamide were ineffective against MES and PTZ induced seizures. Nimodipine, 1 mg/kg, ip, was the most potent agent and produced 100% protection against PTZ. Equieffective doses were pimozide, 25, felodipine, 50, and thioridazine, 50. The rest of the calcium channel blockers showed marginal to moderate activity against chemoshock. The data obtained suggest that some calcium channel blockers possess anticonvulsant activity and may be considered as adjuvant therapeutic agents in epileptics refractory to conventional antiepileptic medication. PMID- 2272646 TI - Effect of pyritinol, a cerebral protector, on learning and memory deficits induced by prenatal undernutrition and environmental impoverishment in young rats. AB - The study was conducted on 64 CF strain albino rats, which were equally distributed into 8 evenly matched groups following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment- vehicle and pyritinol (100 mg/kg, ip). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/pyritinol treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for the passive avoidance learning. The results indicate that undernutrition caused significant original discrimination learning deficits whereas environmental deprivation attenuated both the original and reversal learning performance. Environmental impoverishment attenuated the retention of passive avoidance behaviour but undernutrition had no effect on this paradigm. Pyritinol treatment improved the learning and retention performance of normally reared rats and also attenuated the original and reversal learning deficits induced by parental undernutrition and postweaning environmental impoverishment. The results indicate that pyritinol may be useful in learning and memory deficits induced by malnutrition and environmental deprivation. PMID- 2272647 TI - Hypoglycemic activity of Swertia chirayita (Roxb ex Flem) Karst. AB - Hexane fraction of S. chirayita (250 mg/kg body wt.) induced significant fall in blood sugar and significant increase in plasma IRI simultaneously after single oral administration without influencing liver glycogen concentration in albino rats. On the other hand, daily administration for 28 days resulted in significant lowering of blood sugar and increase in plasma IRI along with a significant rise in liver glycogen. Intestinal absorption of glucose was not inhibited by hexane fraction. It is suggested that hexane fraction of S. chirayita possibly acts through its insulin releasing effect. PMID- 2272648 TI - Screening of Indian plants for biological activity: Part XIV. AB - Alcoholic extracts of 300 botanically identified plant materials from 275 plant species have been tested for various biological activities including chemotherapeutic and pharmacological screenings. Biological activities have been observed in 111 extracts. Follow-up studies have been carried out in some plants with confirmed activity. The active principles and results of these studies are reported. PMID- 2272649 TI - Possible role of C-reactive protein in detoxication of mercury. AB - In mercury-treated rats, C-reactive protein (CRP) has been found to be synthesized in the liver which, in turn, sequesters mercury resulting in the denaturation of the protein into subunits. The subunits retain the mercury and are released into the serum from where it gets excreted. Native CRP and CRP subunits have been found to have different antigenicity. Thus one of the physiological roles of CRP seems to be detoxication of heavy metals. PMID- 2272650 TI - Oral toxicity of Madhuca butyracea Macb. saponins to albino rats. AB - Saponins, isolated from M. butyracea, were assessed for their acute and subacute oral toxicity in albino rats. Acute doses of saponins caused mortalities and LD50 and LD90 values were 330 and 430 mg/kg body wt respectively. Severe diarrhoea, restlessness and histopathological changes were observed in liver and kidney. Diets containing saponins at 0,250,500 and 1000 ppm for 14 weeks did not affect food intake, growth or organ weights, but induced mild histological changes in liver and kidney and altered the serum levels of alkaline phosphatase, blood urea nitrogen, cholesterol and proteins, particularly in female rats. PMID- 2272651 TI - Purification of a metallothionein-like protein from serum of mercury-treated rats using phosphorylcholine-Sepharose affinity column. AB - A metallothionein-like protein (MLP) from the serum of mercury-treated rats was isolated while purifying an acute phase plasma protein, C-reactive protein, by its Ca2(+)-dependent affinity to phosphorylcholine (PC)-Sepharose column. The MLP was further purified by a single DEAE-Sephacel ion-exchange chromatography. The MLP is similar to mammalian hepatic Zn-metallothionein on the basis of its low molecular weight of approximately 7000, 7 g Zn atoms/molecule of MLP and an absorption maximum at 220 nm. The purity of the protein was confirmed by double immunodiffusion test against anti-MLP antiserum raised in a rabbit. Immunologically MLP was detected not only in the hepatic cytosol, serum and urine from Hg-treated rats but also in the serum and hepatic cytosol of untreated rats. Using PC-Sepharose column, MLP could not be purified from normal serum. PMID- 2272652 TI - Effect of chronic cadmium exposure on locomotor behaviour of rats. AB - Growing male rats were exposed to cadmium (Cd, 100 micrograms/kg, ip) for 51 days and the effect on the different components of locomotor behaviour was assessed on days 38, 46 and 51 of Cd exposure. Significant decrease in distance travelled, stereotypic time and movements, ambulatory time and vertical movements were observed in Cd-exposed rats, whereas the time of rest was increased. The number of entries into the inner as well as the outer squares and the total time spent in the inner squares of the floor area were significantly reduced. Results indicate that Cd exposure results in a general depression in all aspects of motor behaviour leading to decrease in gross locomotor activity. The involvement of an exaggerated emotional reactivity in the behavioural expression of the Cd-treated animals is also emphasized. PMID- 2272653 TI - Effect of a new herbo-mineral hypolipidemic agent on plasma lipoprotein pattern in rat atherosclerosis. AB - Hyperlipidemia was induced in rats by feeding an atherogenic diet for 5 months. The effect of administration of an indigenous hypolipidemic agent, Anna Kaara Raaja Sindhooram (AKRS) on the plasma lipoprotein profile was studied in the presence and absence of dietary lipid stimuli. Hyperlipidemia produced an enormous increase in the cholesterol and triglyceride contents of the low density (LDL) and very low density (VLDL) lipoprotein fractions and reduced the level of the putative non-atherogenic high density cholesterol (HDL-C). The agarose gel electrophoretic pattern showed a decrease in alpha-lipoproteins and an increase in beta-lipoproteins in the hyperlipidemic rats. AKRS treatment for 5 months altered the lipoprotein pattern favourably by raising HDL-C and lowering LDL-C in the treated rats. PMID- 2272654 TI - Development of simple and stable ELISA for detection of copro antigen in intestinal amoebiasis. AB - A simple, sensitive and stable ELISA (enzyme linked immunosorbent assay) was developed using rabbit antibody to fractionated Entamoeba histolytica antigen for the detection of copro antigen in the faeces of individuals with intestinal amoebiasis. In this test none of the healthy individuals, all trophozoite positive, 40% cyst passers and 6% individuals living in endemic area showed the presence of copro antigen. ELISA using polyclonal rabbit antibody could detect 1 5 trophozoites/well and 20-50 ng protein per well of NIH-200 strain of E. histolytica and the sensitivity of the test was comparable with that using monoclonal antibody. Cross reaction was observed only with E. invadens when faeces having other parasites were screened. The reagents of ELISA were stabilized and found to be stable for more than 6 months when stored at 4 degrees C. PMID- 2272655 TI - Anti-stress activity in a muramyl-dipeptide. AB - N-Acetylmuramyl-L-alanyl-D-isoglutamine and some of its derivatives have been examined for anti-stress activity. Amongst these, N-palmitoylmuramyl-L-alanyl-D isoglutamine is shown to considerably enhance the capacity of animals to endure various types of stress. This indicates that besides acting as immunomodulators and sleep regulators, muramyl dipeptides may also act as anti-stress agents. PMID- 2272656 TI - Changes in lipid profiles of brain of albino rats following envenomation. AB - Effect of high doses of cobra venom (150 micrograms/120 +/- 20 g body weight) and viper venom (300 micrograms/120 +/- 20 g body weight) on total lipid, triglyceride, phospholipid, cholesterol, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) of brain of albino rats was studied. Total lipid (TL) triglyceride (TG) and phospholipid (PL) are decreased in both viper and cobra venom treated groups while cholesterol (C), and LDL-C are increased in both the groups in relation to controlled ones. HDL-C content was almost unaltered. Decrease in triglyceride and phospholipid may be due to effect of lipases and phospholipases whereas increased cholesterol and LDL C may be attributed to lysis of cell membrane. PMID- 2272657 TI - Age related toxic effects of endosulfan on certain enzymes of rat erythrocytes. AB - The effect of oral administration of endosulfan (12.5 mg/kg body weight), daily for 4 days was investigated on erythrocytes of female rats of 4 different age groups i.e. 15, 30, 70 and 365 days old. Erythrocyte membrane Na+, K(+)-ATPase and Mg2(+)-ATPase activities were significantly inhibited in all the age groups of rats. However, percent inhibition was maximum in the youngest animals. A significant decrease in the activity of erythrocyte glutathione reductase was observed in 30 and 70 days old rats whereas a significant increase in the activity of glucose-6-phosphate dehydrogenase (G-6-PD) was observed in these groups. The increase in G-6-PD activity may be a physiological response to compensate for decrease in the reduced glutathione level which results from decrease in the activity of glutathione reductase. PMID- 2272658 TI - Major histocompatibility complex class I genes of Peromyscus leucopus. AB - Class I genes of the Peromyscus leucopus major histocompatibility complex (MhcPele) were examined by Southern blot hybridization, genomic cloning, and DNA sequencing. At least three distinct subtypes of Pele class I genes were discerned, which we have designated Pele-A, B, and C. The nucleotide sequences of exon 5-containing regions (encoding the transmembrane domain) suggested that Pele A genes are homologs of mouse H-2K, D, L, and Q genes and that Pele-B genes correspond to mouse Tla genes. The Pele-C genes appeared similar to mouse M1 genes. The number of unique genes in each subtype cloned from an individual P. leucopus were 20 for Pele-A, 13 for Pele-B, and 2 for Pele-C. Three genomic clones showed cross-hybridization to both Pele-A and Pele-B gene-specific probes. Six genomic clones remained unclassified as they did not cross-hybridize to exon 5-containing probes from Pele-A, B, or C genes. The homology between the transmembrane domains of Pele class I gene subtypes was found to be similar to that observed between the transmembrane domains of H-2 subtypes (or groups). Interspecific similarity of exon 5 was found to be 81%-88% between Pele class I genes and their H-2 counterparts. PMID- 2272659 TI - Identification of mRNA that encodes an alternative form of H-CAM(CD44) in lymphoid and nonlymphoid tissues. AB - The cluster of differentiation 44 (CD44), hereafter referred to as H-CAM(CD44), represents a novel class of polymorphic (Mr 80,000-215,000) cell adhesion molecules that are involved in cell-cell and cell-matrix adhesion events in a variety of organ systems. We report the detection of distinct mRNAs, in both hematopoietic and nonhematopoietic human cell lines, that encode H-CAM(CD44) with different cytoplasmic domains. Genomic Southern blot analyses indicate that the exons encoding these two cytoplasmic domains are located on the same approximately 16 kilobase (kb) Eco RI restriction fragment. Restriction endonuclease and Southern blot analyses performed on polymerase chain reaction (PCR) amplification copies of these mRNAs confirm that their sequences correspond with previously reported cDNA sequences. A consensus splice donor site which is conserved in human, baboon, and mouse mRNAs that encode a molecule with an elongated cytoplasmic domain (H-CAM-L) is utilized to generate a distinct but low abundance mRNA species that encodes H-CAM(CD44) with a truncated cytoplasmic domain of only three amino acids (H-CAM-S). Estimations of the relative abundance of these mRNA species in B-lymphoblastoid cells using the PCR amplification technique exhibit average H-CAM-L/H-CAM-S ratios ranging between 100 and 200. Therefore, H-CAM (CD44)-mediated adhesive events may be regulated through a differential capacity of H-CAM-L and H-CAM-S to interact with the cytoskeleton and to participate in intracellular signaling events. PMID- 2272660 TI - Genetic basis of the effects of ultraviolet light B on cutaneous immunity. Evidence that polymorphism at the Tnfa and Lps loci governs susceptibility. AB - The ability of local ultraviolet B (UVB) irradiation to impair the induction of dinitrofluorobenzene (DNFB)-specific contact hypersensitivity (CH) in mice has been shown to be genetically determined. We have explored the possibility that the mouse Tnfa and Lps loci are involved. We demonstrate that C3H/HeN (Lpsn) strains are UVB-susceptible, whereas C3H/HeJ (Lpsd) strains are UVB-resistant. Our results indicate that local intradermal (ID) injection of mouse recombinant tumor necrosis factor-alpha (TNFa) into sites painted with DNFB impaired the induction of CH, and in a dose response experiment the effect was found to be more marked in C3H/HeN than in C3H/HeJ. Systemic administration of neutralizing TNFa-specific antibody reconstituted the UVB-induced defect in induction of CH in UVB-susceptible mice, confirming that TNFa is a major mediator of the deleterious effects of UVB on induction of cutaneous immunity. The UVB-susceptibility trait (revealed by effects on CH) correlates positively with a recently described restriction fragment length polymorphism (RFLP) at the Tnfa locus (allele b) and with the wild-type Lpsn allele. These results suggest that appropriate alleles at the Tnfa and Lps loci conspire to render mice susceptible to the impairment of CH induction by UVB. We propose that the mechanism may function through the capacity of UVB to elicit excessive local (cutaneous) production of TNFa, which mediates the immune defect. PMID- 2272661 TI - Sequence and expression of a novel human T-cell receptor beta-chain variable gene segment subfamily. AB - We describe the characterization of a novel subfamily of human T-cell receptor beta-chain variable TCRBV gene segments, detected through homology to a mouse Tcrb-V13 gene segment probe. The new human TCRBV gene segment subfamily TCRBV21 contains three members, all of which have been characterized with respect to nucleotide sequence, chromosomal location, and expression in human thymocytes and peripheral T lymphocytes. Our results indicate that one member of the TCRBV21 subfamily is not expressed in either tissue type although its coding region, promoter, recognition, and splice sequences all appear to be functional at the nucleotide level, possibly indicating regulation at the level of transcription. PMID- 2272662 TI - HLA-DR typing using DNA amplification by the polymerase chain reaction and sequential hybridization to sequence-specific oligonucleotide probes. AB - A series of sequence-specific oligonucleotides (SSOs) have been used to type alleles at the HLA-DRB1 locus. Genomic DNA was amplified to high copy number by the polymerase chain reaction (PCR) and hybridizations of the dot-blotted, amplified DNA to a series of 14 SSOs enabled the identification of the major specificities DR1-DRw14. Certain alleles (DR3 and DR4) could be rapidly and accurately identified by running the products of allele-specific amplification of genomic DNA on agarose gels. This approach facilitated the typing of serological specificities such as subtypes of DR3 (DRw17 and DRw18) as well as alleles previously detected by the mixed lymphocyte reaction including subtypes of DR4 (Dw4, Dw10, Dw13, Dw14, and Dw15). The HLA-DR types obtained by SSO probing conformed to rules of Mendelian inheritance when they were applied to a series of 75 families. A full DR type could be obtained from many individuals simultaneously without needing to separate or store viable lymphocytes. Thus, this technique may have considerable implications for the analysis of disease associations with HLA class II alleles, particularly in circumstances where facilities for the initial preparation and storage of the samples may be limited. PMID- 2272663 TI - Molecular analysis of the human MHC class I region using yeast artificial chromosome clones. AB - The cloning of large genomic fragments corresponding to the major histocompatibility complex (MHC) class I region provides the necessary framework for a better understanding of its organization and for the localization of new genes involved in MHC-associated disease. Two human genomic libraries constructed in yeast artificial chromosomes (YACs) have been prepared using complete Not I or Mlu I digestion of source DNA. From these libraries three YAC clones with inserts belonging to the MHC class I region have been isolated. They correspond to exact copies of three genomic fragments of 210, 145, and 50 kilobases (kb), respectively and have been precisely located in the restriction map of the region. Detailed rare-cutter restriction maps of the inserts have been generated. Within these clones we have demonstrated the presence of two class I genes, one of which is HLA-E, and of at least three Hpa II tiny fragment (HTF) islands, corresponding to three putative new transcribed sequences. End clones, which are of particular interest in the extension and refinement of the regional map, have been rescued by systematic subcloning of purified YACs. PMID- 2272664 TI - Complement C4 and heat shock protein 70 (HSP70) genotypes and type I diabetes mellitus. AB - Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype. PMID- 2272665 TI - Three extra copies of a C4-related gene in H-2w7 mice are C4/Slp hybrid genes generated by multiple recombinational events. AB - Mice bearing the H-2w7 haplotype have five C4-related genes and constitutively express the Slp antigen. To understand the structure and evolution of the five C4 related genes of the C3H.W7 mouse, we have determined nucleotide sequences of the 5' end region of these genes. A C4/Slp hybrid nature was confirmed for three of five C4-related genes as predicted previously by restriction enzyme analysis. The nucleotide sequences of the 5' flanking regions of these three hybrid genes showed close similarity to that of the C4 gene, while the 3' side of the ninth exon of the three hybrid genes showed close similarity to that of the Slp gene. In contrast, the regions between the first exon and the middle of the ninth exon of the three hybrid genes showed a mosaic structure of C4-like and Slp-like sequences. Moreover, the boundaries of the C4-like and Slp-like sequences were quite different among the three hybrid genes. The pattern of nucleotide sequence diversity in this region among the five C4-related sequences could be mainly explained not by point mutations but by gene conversions or unequal crossovers. These results suggest that multiple genetic recombinational events between two homologous sequences played an important role in the generation and diversification of the extra copies of the C4/Slp gene in the H-2w7 mouse. PMID- 2272667 TI - Locus-specific cDNA cloning in the class I multigene family: structure of H-2Dr and H-2Ds. PMID- 2272668 TI - Cytogenetic studies in Hodgkin's disease. AB - Chromosome studies were carried out by G-banding technique on the bone marrow cells of 24 newly diagnosed, untreated Hodgkin's disease patients and 25 treated patients. Seven of these treated patients had also been studied at diagnosis. In the untreated group of patients, cytogenetic studies were carried out on stimulated peripheral blood lymphocytes in 11 patients and on skin fibroblasts in five. Of the 24 untreated patients, 14 showed normal diploid pattern, while 10 were seen with 8-30 per cent chromosomally aberrant cells in the bone marrow. The frequent anomalies were trisomy C/8 and trisomy 22 seen in 5 and 4 patients respectively. The cytogenetic picture of peripheral blood lymphocytes revealed normal diploid pattern in 7 patients; while 4 other patients showed abnormal clones with trisomy 21. The cultured skin fibroblasts represented normal diploid karyotypes. An altered karyotypic pattern was seen in the bone marrow of treated patients. In patients with abnormal karyotypes, the common anomalies were monosomy C, monosomy D/15 and trisomy 21. In patients which showed no involvement of the bone marrow by haematological parameters, chromosomally abnormal karyotypes were seen in the marrow. Thus, marrow involvement can be detected earlier cytogenetically. PMID- 2272666 TI - High-resolution one-dimensional isoelectric focusing of mouse MHC class I antigens. Identification of natural and experimentally induced class I antigens. AB - A method is described for a biochemical comparison of mouse class I antigens utilizing antisera with a monomorphic pattern of reaction and high-resolution one dimensional isoelectric focusing (1D-IEF). The most commonly occurring and studied H-2K and D alleles were identified in a comparison of over 40 mouse strains. By comparing H-2 mutant mouse strains, cell lines transfected with defined class I genes, or mice transgenic for a mouse class I gene and H-2 recombinant mouse strains, unambiguous identification of class I alleles was possible. The complex pattern presented by H-2-heterozygous mice was readily resolved into the contribution by the individual parental alleles. The H-2b bm series of mutants was analyzed, and for those mutants where a charge difference was predicted based on their known sequence, a change in isoelectric point (IEP) was indeed observed. Based on analysis by IEF, the bm8 mutant may contain (an) amino acid substitution(s) in addition to those reported. The present method further appears useful in elucidating defects in class I antigen synthesis and post-translational modifications, as these cannot be easily characterized when using surface staining with monoclonal antibodies (mAbs). PMID- 2272669 TI - A clinico-pathologic study of pituitary adenomas. AB - One hundred patients of pituitary adenoma were studied using light microscopy, electron microscopy, immunohistochemistry and serum hormone estimation. Depending on the absence or presence of clinical endocrine manifestation they were divided into 2 groups 'non-functioning' (group I -48 patients) and 'hyper-functioning' (group II- 52 patients). Tumours in group I were chromophobes, some of which (group IA) had no hormone increase in serum nor detection in tissues and ultrastructurally they consisted of secretorily inactive cells (null cell adenomas) while others (group IB) were composed of secretorily active cells with prolactin consistently increased in serum and localized in tissue (lactotroph adenomas). Tumours in group II were chromophobe, acidophil, basophil or mixed adenomas with varying number of secretorily active cells in all. The hormone responsible for the hyperfunction was always raised in serum and localized in tissue. Thus growth hormone was demonstrated in all tumours from patients with acromegaly (somatotroph adenomas), prolactin in all tumours from patients with galactorrhea (lactotroph adenomas) and ACTH in all tumours from patients with Cushing's syndrome (corticotroph adenomas). It was observed, however, that 40 per cent of tumours were pleurihormonal, growth hormone and prolactin being the commonest combination. Interestingly, not all the hormones localized by immunohistochemistry in pleurihormonal adenomas were detected in serum and/or reflected in the clinical picture. PMID- 2272670 TI - In vitro effect of intravenous immunoglobulin on serum opsonic activity in normal & intrauterine growth retarded neonates. AB - In vitro effect of intravenous immunoglobulin (IVIG), Intraglobin F, on serum opsonic activity against Staphylococcus aureus was studied in 26 full term normal healthy neonates and 18 intrauterine growth retarded (IUGR) neonates by the polymorphonuclear leucocyte overlay method (requiring only a few drops of blood). Cord IgG and IgM levels were determined by single radial immunodiffusion. Serum opsonic activity against Staph. aureus was significantly lower in the IUGR neonates (49.1 +/- 0.89), as compared to that in normal neonates (61.96 +/- 0.73; P less than 0.001). Immunoglobulin supplementation in vitro at a concentration of 5 g/dl significantly enhanced the opsonic activity of IUGR neonate sera. Cord IgG levels of IUGR neonates were significantly lower (P less than 0.01) than IgG levels of normal neonates. No significant difference was observed in cord IgM levels between the normal and IUGR neonates. PMID- 2272671 TI - Effect of giardia infection on nutritional status of preschool children. AB - Nutritional status of 34 children aged 24-72 months and infected with giardia was compared with that of 92 children matched for age, sex and income and 34 children matched for age, sex, income as well as birth order. Children without giardiasis were found to have better nutritional status in both comparisons. The difference was more pronounced in the second instance. Of the seven anthropometric parameters used for comparison, four were significantly lower (weight, weight for age, midarm circumference and midarm circumference for age), while two (height for age and weight for height) showed nonsignificant childhood malnutrition and that matching for birth order enhances the utility of case-control studies in children. PMID- 2272672 TI - Electrophysiological studies on human phrenic nerve & diaphragm. AB - To determine normal values for phrenic nerve stimulation, the phrenic nerve was stimulated transcutaneously in 22 healthy adolescent male volunteers. The phrenic latency, amplitude and duration of the evoked diaphragm action potential (EDAP) were noted. Maximum mouth inspiratory pressure (MMIP) and maximum ventilation volume (MVV) were also measured to evaluate the maximal strength of the diaphragm. No significant correlations were observed between EDAP and the parameters of diaphragm strength. The correlation coefficient between the amplitude-duration product of EDAP (integral EDAP) and MMIP was +0.15 and it was +0.29 between the integral EDAP and MVV. PMID- 2272673 TI - Intra-individual variation in energy intake in adult males in training. AB - Variability of energy intake was examined using data for 73 adult males (17-21 yr) for two different levels of training. The subjects were put on hard physical training costing about 1850 kcal/d (phase I: heavy activity) for the first five months and trades' training involving light physical work equivalent to 900 kcal/d (phase II: moderate activity) in the next five months. All the subjects were observed for five consecutive days of their training for dietary intake, weight, and daily activity pattern in the middle of each activity level. A subsample of nine subjects was also surveyed for five consecutive days every second month during the entire training period to get an estimate of week to week variation within subjects. 'Weigh as you eat' method in combination with proximate analysis was used to determine the habitual energy intake of the subjects. Analysis of variance for intake data showed that a substantial part (55 to 60%) of the total variance was contributed by intra-individual variation. Inter subject variation was found to have a cv of 10 per cent in both the levels of activity. Moreover data of the subsample indicated that variation in mean intake from week to week was significantly larger than the daily variance suggesting nonrandomness of daily energy intake. PMID- 2272675 TI - High frequency resonant oscillations technique to improve nasal muco-ciliary transport. AB - A modified high frequency resonant oscillations (HFRO) technique was developed to improve the nasal muco-ciliary transport in patients with impaired ciliary functions due to various chronic diseases of the upper respiratory tract. Twelve healthy males (group I) and ten patients suffering from malignancy of the upper respiratory tract (group II) were exposed to HFRO in order of 200, 250, 300, 400, 500 Hz respectively. The muco-ciliary transport (MCT) was assessed by using saccharine clearance time technique. A significant improvement in MCT was observed in both the groups at all the frequency levels, more so in the range of 400 and 500 Hz. An overall relative improvement of 174 per cent (P less than 0.01) in group I and 145 per cent (P less than 0.001) in group II was observed. No significant side effects were noted. PMID- 2272674 TI - Effects of medial septal stimulation & its blockade with atropine on hippocampal rhythmical slow activity in free-moving rabbits. AB - The influence of the medial septal nucleus (MSN) on hippocampal rhythmical slow activity (RSA) was investigated in hunger motivated free-moving rabbits. Single unit activity of 29 CA3 dorsal hippocampal neurones was studied under two paradigms viz., electrical stimulation (3v/1msec/5Hz) and chemical blockade of atropine-sensitive medial septal cells (dose of 5 micrograms in 5 microliters). The analysis of interspike interval sample histograms recorded with Apple II, along with single unit neuronal spikes recorded on polygraph showed bimodal pattern with two peaks; one at bin 10-20 (high frequency) and second at bin 100 300 (theta frequency). On stimulation of MSN, there was total suppression of bin 100-300 with peaks at bin 1-20 and at bin greater than 1000 (very low frequency). Blockade of cholinergic receptors at MSN showed reduction of bin 100-300 and peak at bin 700- greater than 1000; this was followed by gradual decrease of spike's amplitude and thereafter its total abolition. The results indicate that the septal region is not a pacemaker per se in the genesis of hippocampal RSA (theta rhythm), but serves more in the nature of a relay station for a number of inputs and that its influence on the hippocampal electrical activity depends on the integrity of cholinergic inputs, be it from hippocampus proper or from mid-brain reticular formation. PMID- 2272676 TI - Biochemical studies of liver & liver microsomes in envenomated rats. AB - Some biochemical parameters of liver and liver microsomes were studied in albino rats following administration of cobra and viper venoms at dose of 2 mg/kg body weight. The total protein content in cobra venom treated (CVT) animals and DNA and RNA contents of liver and liver microsomes were almost unaltered in both the venom treated animals while total protein content was significantly reduced in viper venom treated (VVT) animals. Alkaline and acid phosphatases activities of whole liver showed significant increase in both the venom treated animals whereas the rise in cholinesterase activity in CVT animals was not significant. Lactic acid content was significantly higher in CVT animals compared to either VVT animals or controls. The glycolytic enzymes viz., aldolase, phosphohexose isomerase and lactate dehydrogenase measured in hepatic microsomal fraction were significantly reduced while alanine and aspartate aminotransferases and gamma glutamyl transpeptidase activities of liver microsomes were significantly elevated in both the venom treated animals compared to controls. PMID- 2272677 TI - Membrane-associated protease activity of human erythrocytes. AB - Membrane-associated protease activity capable of digesting a number of membrane cytoskeletal proteins including band 3 protein was identified in human erythrocytes, almost totally free from contaminating leucocytes and platelets. This enzyme was inhibited by aprotinin (a specific inhibitor for a class of serine protease) and was distinct from the cytosolic calcium-dependent thiol protease (calpain), which is also known to bind to red cell membrane. PMID- 2272678 TI - Effect of feeding black gram (Phaseolus mungo) on serum lipids of normal & diabetic guineapigs. AB - When normal and alloxan-induced diabetic guineapigs were given whole seed diet of Phaseolus mungo (black gram) for 4 wk, the blood glucose, serum total lipids, triglycerides and esterified fraction of cholesterol were significantly lowered, while serum phospholipid was unaltered. Total cholesterol/phospholipid ratio also decreased in normal as well as diabetic animals indicating the antiatherogenic nature of P. mungo. PMID- 2272679 TI - Radial keratotomy--a decade's perspective. PMID- 2272680 TI - Radial keratotomy: procedures. AB - The presently employed procedure of radial keratotomy is essentially unchanged from that developed by Fyodorov and introduced into the United States by Bores in 1978. The surgical procedure essentially consists of six basic steps: 1) application of appropriate anesthesia; 2) marking the visual axis; 3) marking the optical zone; 4) measuring the corneal thickness; 5) setting the depth of the blade; and 6) marking the corneal incisions. This review will carefully consider the pros and cons of many potential variations associated with each of these steps. PMID- 2272681 TI - Three year results of the Prospective Evaluation of Radial Keratotomy (PERK) study. AB - The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center clinical trial of a standardized technique of radial keratotomy in 435 patients who had simple myopia with a preoperative refractive error between -2.00 and 8.00 diopters (D). We report results for one eye of each patient. The surgical technique consisted of eight incisions using a diamond micrometer knife with the blade length determined by intraoperative ultrasonic pachymetry and the diameter of the central clear zone determined by the preoperative refractive error. At three years after surgery, 58% of eyes had refractive error within one diopter of emmetropia; 26% were undercorrected, and 16% were overcorrected by more than one diopter. Uncorrected visual acuity was 20/40 or better in 76% of eyes. The operation was more effective in eyes with a preoperative refractive error between -2.00 and -4.37 diopters. Between one and three years after surgery, the refractive error changed by 1.00 diopter or more in 12% of eyes, indicating a lack of stability in some eyes. PMID- 2272682 TI - Surgical correction of postoperative astigmatism. AB - The photokeratoscope has increased the understanding of the aspheric nature of the cornea as well as a better understanding of normal corneal topography. This has significantly affected the development of newer and more predictable models of surgical astigmatic correction. Relaxing incisions effectively flatten the steeper meridian an equivalent amount as they steepen the flatter meridian. The net change in spherical equivalent is, therefore, negligible. Poor predictability is the major limitation of relaxing incisions. Wedge resection can correct large degrees of postkeratoplasty astigmatism, Resection of 0.10 mm of tissue results in approximately 2 diopters of astigmatic correction. Prolonged postoperative rehabilitation and induced irregular astigmatism are limitations of the procedure. Transverse incisions flatten the steeper meridian an equivalent amount as they steepen the flatter meridian. Semiradial incisions result in two times the amount of flattening in the meridian of the incision compared to the meridian 90 degrees away. Combination of transverse incisions with semiradial incisions describes the trapezoidal astigmatic keratotomy. This procedure may correct from 5.5 to 11.0 diopters dependent upon the age of the patient. The use of the surgical keratometer is helpful in assessing a proper endpoint during surgical correction of astigmatism. PMID- 2272683 TI - Radial keratotomy. AB - Radial keratotomy has always produced ambivalent feelings in the Ophthalmologist. The severe complications produced by the Sato procedure has been an unforgettable episode. The work of Fyodorov and Durney (1979) and their American counterparts, Bores (1981) and Hoffer (1981) have done a great service to radial keratotomy in having it established as an acceptable procedure. The controversy really only abated with the work of the National Institute of Health Funded Prospective Evaluation of Radial Keratotomy (PERK) study which suggested that the procedure has a low initial risk and was effective in decreasing myopic correction. Over the last 3 years a series of cases where evaluated and followed up in detail in an effort to gain a perspective on the one problem which has bugged the radial keratotomy programme from the beginning-its predict-ability. PMID- 2272684 TI - Complications of radial keratotomy: review of the literature and implications for a developing country. PMID- 2272685 TI - Radial keratotomy in India untoward consequences and complications. AB - R.K. is a surgery of tomorrow. It is still in the stage of evolution. It should be under-taken only for precise indications. Case evaluation and honest advice to the patient is important. The patient should be explained that the worst can happen. The surgery should be limited to moderate degrees of myopia, not less than -3.0 D sphere and not more than 8 to 10 D. It has no place for myopia with degenerative retinal changes. Surgery should be interrupted at the first sign of a significant operative complication. It will be unfortunate if a healthy eye is lost due to complications of R.K. done with indiscriminate approach and ignorance of possible post-operative consequences. PMID- 2272686 TI - Live male adult W. bancrofti in the anterior chamber. PMID- 2272687 TI - [Concepts in removable partial dentures. 1. Enclosed lateral edentulism]. PMID- 2272688 TI - [Irritative gingival fibroma and peripheral giant cell granuloma]. PMID- 2272689 TI - [Interligamentary anesthesia in pediatric dentistry]. PMID- 2272690 TI - [Restoration of incisal function with ceramic bonding in a fracture case]. PMID- 2272691 TI - [Sanguinarine. Its role in periodontal therapy]. PMID- 2272692 TI - [Arthroscopy of the temporomandibular joint. Diagnostic and therapeutic relations]. PMID- 2272693 TI - [Treatment of lateral maxillary incisor agenesis with bonded bridges]. PMID- 2272694 TI - [Appointment book management]. PMID- 2272695 TI - [Priority objective for the new dentist]. PMID- 2272696 TI - Raising expectations for grandparents: a three generational study. AB - Previous research resulted in the nation's first curriculum for grandparents. To determine the program benefits, 210 experimental subjects received instruction. Each of these persons chose one son or daughter and one grandchild to help evaluate changes in grandparent attitudes and behavior. All three generations completed separate versions of the Grandparent Strengths and Needs Inventory prior to the classes, at the end of intervention, and three months later. Posttesting of grandparents revealed significant improvement. These gains were corroborated by parents and grandchildren. Multivariate analyses identified the impact of eleven independent variables on grandparent performance. A control group of 185 subjects made no improvement. PMID- 2272697 TI - The grandparent role: a double bind. AB - In response to open-ended questions, married and single mothers described advantages and disadvantages of having grandparents in the family. Single mothers emphasized the value of grandparents' practical and moral support in childrearing; married mothers more often stressed grandparents' value in providing family heritage and stability. Married and single mothers agreed that grandparents' interference in childrearing could pose threats to family harmony. It is proposed that grandparents may face a double bind in attempting to meet parents' expectations: parents may expect grandparents to simultaneously be supportive without interfering. This double bind may be particularly poignant for grandparents in single mother families. PMID- 2272698 TI - Husbands' and wives' perceptions of marital fairness across the family life cycle. AB - Marital fairness, or the subjective balance between two spouses' gains and losses, was evaluated by a cross-sectional sample of 134 married Australian men and women representing five phases in the family life cycle: preparental, childbearing, the full house, launching, and the empty nest. Husbands' perceptions of their own marital equity described a U-shaped curve across these phases, with significantly more men feeling equitably treated both initially and after children's departure than during any of the three phases with children in the home. Wives' perceptions, by contrast, showed little variation with life cycle phase. Overall, a slight majority (52 percent) of husbands and wives perceived their marriages as equitable. Both sexes were inclined to agree, however, that whenever deviations from strict marital equity arose during family life, these were most likely to overbenefit husbands and to underbenefit wives. Results are discussed in relation to 1) equity theory, 2) marital satisfaction research, and 3) Bernard's model of the intrinsic sexual inequality of marriage as an institution [1]. PMID- 2272699 TI - The long-term marriage: perceptions of stability and satisfaction. AB - Marriage has been shown to be conducive to the well-being of both men and women. An increasing proportion of older people, however, are likely to live alone because of the high divorce rate. This research raises the question of what factors might be involved in a stable and satisfying marriage. Data were gathered from 100 couples who have been married forty-five years or more. The variables identified by couples as important to their marriages were: being married to someone they liked as a person and enjoyed being with; commitment to the spouse and to marriage; a sense of humor; and consensus on various matters such as aims and goals in life, friends, and decision making. Husbands and wives were strikingly similar in their responses; thus, men and women perceive the same variables to be critical in the success of long-term marriages. PMID- 2272700 TI - The call to vocation: life histories of elderly women religious. AB - Thirty elderly women religious (Catholic nuns) were studied using a phenomenological interview technique. This paper discusses the women's "call to vocation"--the remembered life events that influenced their decisions to enter the convent as young girls. The women talked about romantic and pragmatic motivations as well as spiritual direction. Remembrances of three of the study participants are used to demonstrate circumstances and emotions that led the women to choose their life course. The recollections have significance for the women religious in late life; they provide a source of satisfaction and commitment. They also offer researchers a means of viewing the worlds of this population of women. PMID- 2272701 TI - Socio-economic predictors of alienation among the elderly. AB - A study of 200 older clients of senior service centers in a metropolitan area was conducted to determine their level of alienation and the extent to which selected socio-economic variables (race, education, income, health, living arrangement, church work, and volunteer work) were associated with four subtypes of alienation. Group isolation and powerlessness were found to be much more prevalent than personal isolation or normlessness. Health, race, education, and income were found to be the strongest predictors of alienation. Higher levels of alienation were found among older blacks, and those with lower health rating, lower education, and lower income, compared to their opposites. The implications of the findings are discussed. PMID- 2272702 TI - Cherished possessions and adaptation of older people to nursing homes. AB - One hundred older people (75 females, 25 males), in nursing homes rated as above or below a combined criterion (based on Lieberman and Tobin's scales of physical attractiveness, affiliation fostering, and tolerance for deviancy), responded to questionnaires on cherished possessions and on adaptation to the nursing home. The main findings indicated: 1) relative to those residents without possessions, those with possessions were better adapted to the nursing home; 2) possessions served the major functions of historical continuity, comforter, and sense of belongingness; 3) relative to men, significantly more women had cherished possessions and were more likely to associate them with self-other relationships; and 4) relative to residents in nursing homes below the mean of the combined criterion, those in homes above the mean felt more in control, less helpless, more supported by staff, and were judged as more realistic in response to conflict. Interpretations regarding the role of possessions in adaptation and suggestions for institutional policies concerning possessions are discussed. PMID- 2272703 TI - Amiodarone--efficacy and late potentials during long-term therapy. AB - This prospective study was intended to examine the influence of long-term amiodarone therapy on the parameters of the signal averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose 27 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and highgrade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after two months and subsequently every three months if possible, a resting ECG, a signal averaged ECG by the method of Simson and Holter monitoring were performed. Compared to the initial measurement we found a significant increase in the duration of the total filtered QRS complex, while the change in the voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone. In the long-term follow up Holter monitoring showed a relatively high responder rate of between 46 and 81% under amiodarone. No relation could be detected between the results of the signal averaged ECG and those of 24-h Holter monitoring. PMID- 2272704 TI - Effects of ketanserin administration on lipid metabolism and platelet aggregation in hypertensive patients. AB - Lowering blood pressure is not totally effective in preventing the atherosclerotic complications of systemic hypertension. In hypertensive patients both platelet hyperaggregation and dyslipidemia have been suggested as important risk factors. The effect of 8 weeks' treatment with ketanserin on blood pressure, serum lipid parameters (cholesterol, triglycerides, LDL, HDL-C, apolipoprotein A1 and B) and platelet aggregation, induced by collagen, ADP, arachidonic acid, was evaluated in 10 patients with essential hypertension. Ketanserin was effective in lowering blood pressure in all patients, 6 of whom became normotensive. Both CHOL and TG levels and APO B were significantly reduced, whereas HDL-C and APO A1 were significantly increased after treatment. These results might be attributed to the antagonistic activity of ketanserin on alpha-1 adrenoceptors with a consequent inhibition of phosphodiesterase. Platelet aggregation, after stimulation with collagen and arachidonic acid, was significantly reduced secondary to the inhibition of intraplatelet serotonin synthesis and release. These results suggest that keranserin is effective in reducing blood pressure and in achieving normal serum lipid pattern and platelet aggregation. Therefore, this drug might be helpful in controlling the main risk factors for cardiovascular damage. PMID- 2272705 TI - Interaction between nifedipine and cardioactive drugs. AB - Nifedipine (N) and dehydronifedipine (DHN) plasma levels were measured by gas chromatography in 37 patients before and 2 h after the intake of 20 mg N. They suffered from cardiovascular diseases and were treated with N in daily doses of 30 or 60 mg in combination with nitrates, beta-receptor blocking agents, digitoxin, saluretics and/or vasodilators for several weeks or months. Simultaneously, blood pressure and heart rate were measured. For comparison, six healthy volunteers between the ages of 25 and 46 years took 20 mg N on an empty stomach. Their mean plasma N level amounted to 47.7 (SD: 13.6) ng.ml-1, the DHN level reached a mean value of 46.7 (SD: 22.8) ng.ml-1 2 h after administration. The mean plasma N level of the patients rose from 14.1 to 34.1 ng.ml-1 and that of DHN, from 5.4 to 16.0 ng.ml-1. In 26 of 37 patients the heart rate increased without correlating with the altitude of the N level. The ratio DHN/N was 0.83 (SD 0.24) in the volunteers, while in the patients it amounted to 0.59 (SD 0.30). If the criterion DHN/N plasma level reached values greater than 1.0 the N degradation was enhanced (n = 4), and if it reached values less than 0.2, N degradation was depressed (n = 9). The results did not indicate inhibition of N degradation under long-term treatment with simultaneously administered cardioactive drugs. PMID- 2272706 TI - Biliary pharmacokinetic profile of piperacillin: experimental data and evaluation in man. AB - The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, this work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 +/- 305 micrograms/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2 g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 +/- 601 micrograms in 4 h (0.08% of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 +/- 64 micrograms/ml during the 2nd h, and the 24 h biliary elimination was 12,963 +/- 3,332 micrograms, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 +/- 20.5, 382 +/- 110, 30.8 +/- 2.5 micrograms/ml and 10.5 +/- 2.6 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272707 TI - Bioavailability of doxycycline from dissolved doxycycline hydrochloride tablets- comparison to solid form hydrochloride tablets and dissolved monohydrate tablets. AB - Doxycycline (DC) is used either as solid form hydrochloride capsules, or as monohydrate tablets, which may be taken either as solid form tablets or dissolved in water. In this single dose (150 mg), crossover study on 15 healthy volunteers, the pharmacokinetic properties of DC from hydrochloride tablets taken either in dissolved or in solid form were compared with those observed after taking dissolved DC as a monohydrate tablet. The results of this study show that DC is absorbed rapidly (tmax 3.3-3.8 h) and with equal bioavailability (AUC values 52.9 58.5 mg/l x h) from both hydrochloride and monohydrate tablets. It can be concluded that taking the DC hydrochloride tablets in dissolved form does not affect the pharmacokinetics of DC, moreover the bioavailability of DC is comparable to that achieved after taking DC monohydrate tablets in dissolved form. PMID- 2272708 TI - Effect of calcium and calcium blockers in hypertension. AB - Calcium is important in the maintenance of arterial smooth muscle function and its alteration from normal may predispose to atherogenesis and hypertension. Slow channel inhibitors such as nifedipine and calcium salts have been used separately to modulate arterial calcium in patients with hypertension. This study included 41 patients with essential hypertension, of whom 29 responded to calcium gluconate therapy (9.8/6.3 mmHg) and the remaining 12 (group B) showed either no response or a rise in blood pressure. Combined administration of calcium and nifedipine in responders (29 cases, group A) in a single-blind, placebo controlled manner showed a further substantial decrease (9.6/3.2 mmHg) in pressure compared with pressures during placebo administration in both short- as well as long-term administration in group B patients. Although it is difficult to predict the positive role of calcium in hypertension, non-obese females with increased salt intake show a greater response to calcium therapy. It is possible that calcium salts plus calcium blocker therapy can further reduce the blood pressure in a particular subset of hypertensives. However, this needs further confirmation in a larger study. PMID- 2272709 TI - Cimetidine pharmacokinetics after oral administration of cimetidine retard in normal and impaired renal function. AB - Cimetidine pharmacokinetics was investigated in four groups: Group I with three normals (serum creatinine less than 1.5 mg/dl), Group II with three kidney patients, renal function slightly impaired (serum creatinine greater than 1.8-4.3 mg/dl), Group III with three patients suffering from severe impairment (serum creatinine greater than 4.3 mg/dl) and Group IV with three patients on chronic hemodialysis. All four groups were given cimetidine retard (350 mg tablets Neutronorm retard, Ebewe Arzneimittel GmbH, A-4866 Unterach a.A., Austria). Groups I and II (normals and slightly impaired renal function) received the tablets twice a day with an interval of 12 h (7:00 a.m. and 7:00 p.m.). Groups III and IV (severely impaired renal function and hemodialysis patient were only given one dose a day (7:00 a.m.). The group of normals (I) and the group with slightly impaired renal function (II) had the highest serum cimetidine concentrations one to two h after the morning dose, followed by an exponential decrease. After the evening dose in Group I, the highest concentrations were found after 4 h. Group II had the highest concentrations four to eight h after administration. Compared to the morning dose, the exponential decrease of the serum cimetidine concentration was delayed in onset and slower in phasing out. Furthermore, concentration was higher during the night than during the day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272711 TI - Phenocopy and pharmacogenetics. An issue for controversy? PMID- 2272710 TI - beta-Glucuronide and sulfate conjugation of scopolamine and glycopyrrolate. AB - The metabolism of scopolamine and glycopyrrolate was studied in 11 healthy parturients undergoing cesarean section. After a single intramuscular injection of scopolamine (5 micrograms/kg, n = 7) or glycopyrrolate (6 micrograms/kg, n = 4), the concentrations of the drugs in the urine were determined up to 8-12 h using a radioreceptor assay. This assay measures scopolamine and glycopyrrolate with their possible active metabolites. The effect of beta-glucuronidase and sulfatase incubation on the drug concentrations was also studied. The concentrations of scopolamine and/or its active metabolites were on the average 7 times higher after incubation indicating that beta-glucuronide or sulfate conjugation is an important metabolic pathway for scopolamine. On the contrary, the glycopyrrolate concentrations increased only slightly between 1 and 3 hours after the drug injection. Thus, beta-glucuronide or sulfate conjugation plays only a minor part in the metabolism of glycopyrrolate. PMID- 2272712 TI - Standardization of definitions and criteria of causality assessment of adverse drug reactions. Drug-induced liver disorders: report of an international consensus meeting. AB - International reporting of adverse drug reactions by pharmaceutical manufacturers to national drug regulatory authorities requires internationally accepted standard definitions of reactions and criteria for assessment of causality. The Council for International Organizations of Medical Sciences (CIOMS) undertook a pilot project to prepare such definitions and criteria, and proposed to use as its model a series of expert consensus meetings organized in France by the pharmaceutical company, Roussel Uclaf, with the participation of the official French network of pharmacovigilance. Under CIOMS auspices, an international meeting was organized to test the feasibility of adapting for international use the outcome of the French consensus meetings on drug-induced liver disorders. The meeting resulted in a series of proposed standard designations of drug-induced liver disorders and criteria of causality assessment. PMID- 2272713 TI - Influence of vinpocetine on warfarin-induced inhibition of coagulation. AB - The influence of 14 days of concomitant vinpocetine administration on prothrombin time prolongation of single 25 mg doses of warfarin was investigated. Eighteen male subjects were included in the study. They received 25 mg warfarin the first day. Prothrombin time, warfarin plasma levels and factor VII coagulation time were monitored on days 1-5. Ten mg vinpocetine was administered from day 6 to 24. Another single dose of 25 mg of warfarin was given a second time on day 20. AUC values of prothrombin time, warfarin plasma level and factor VII clotting time curves and appropriate Cmax and tmax plasma levels of days 20-24 were compared with those of days 1-5. The confidence interval limits of the ratio of AUC20 24/AUC1-5 of prothrombin time curves were within the limits of 0.8 and 1.2, so that the formal criteria of equivalent biological activity were met. However, a minute influence probably without clinical implication is likely since both point estimate as well as confidence interval limits were below 1. PMID- 2272714 TI - Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly). AB - Metformin efficacy and safety in type 2 diabetes has not been studied in the elderly patient under conditions pertaining to clinical practice. We have therefore, studied prospectively over two months 24 patients aged between 70-88 years with 115% mean ideal body wt and glycemic control greater than 10 mol.l-1 fasting and/or greater than 14 mol.l-1 postprandial, and/or an HbA1 value greater than 10%. At entry into the study, patients were on metformin + sulfonylurea (n = 15), sulfonylurea (n = 3), metformin (n = 2), insulin (n = 1) or diet alone (n = 3). They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively. Compared to pretreatment values, glycemic control at 1 and 2 months were unchanged, with metformin blood levels remaining within expected values for both dosage groups. Blood lactate levels remained unchanged in the high dosage group but were reduced (p less than 0.05) on 850 mg/day probably because of the reduction of metformin dosage in patients already treated prior to the study. It is concluded that provided the dosage is adjusted to renal function, the metabolic tolerance of metformin therapy is satisfactory in the elderly type 2 diabetic patient. With regard to efficacy, longer observations are needed to know whether this therapy may offer on a long-term basis equivalent glycemic control compared to other treatment modalities. PMID- 2272715 TI - Changing pattern of antimicrobial utilization in an Indian teaching hospital. AB - A study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, on the pattern of antimicrobial utilization in hospitalized patients. A retrospective study was conducted during a one-month period between January 18 to February 17, 1987. The data were analyzed according to modified Kunin's criteria. The results were compared with a similar study conducted a decade ago. The study revealed a marked increase in the use of antimicrobial agents (from 19.9% to 56.1%). A more appropriate use of antimicrobial agents was observed (from 66.8% to 79.5%). A significant increase in their appropriate use for therapeutic purpose (50% to 88.2%), but not for prophylaxis (79.05% to 71.18%) was seen. The study revealed a marked increase in the use of antimicrobial agents during the last decade resulting in the emergence of nosocomial infections of resistant strains of organisms. PMID- 2272716 TI - Pharmacokinetics of triflusal after single and repeated doses in man. AB - Triflusal pharmacokinetics were evaluated in 8 healthy subjects after a single 300 mg dose and after repeated doses of 300 mg every 8 h and 600 mg every 24 h during 13 days, with the aim of establishing a relationship between plasma levels and dosage patterns. Plasma concentrations of triflusal and its main metabolite, 2-hydroxi-4-trifluoromethylbenzoic acid (HTB), were determined by HPLC. Triflusal (t1/2 = 29-35 min) metabolized rapidly into HTB. Four h after the first or last repeated dose administration, triflusal levels could not be detected. After the administration of 300 mg every 8 h, the parameters obtained for HTB were: Cmax-ss = 178 +/- 42 micrograms/ml, tmax-ss = 1.9 +/- 0.7 h, Cmin-ss = 155.6 +/- 41.2 micrograms/ml, Cavg-ss = 168.0 +/- 41.8 micrograms/ml and a t1/2 of 48 +/- 15 h. The parameters obtained for the dosage of 600 mg every 24 h were: Cmax-ss = 153 +/- 40 micrograms/ml, tmax-ss = 2.7 +/- 0.9 h, and a t1/2 of 50 +/- 16 h. No significant differences were observed between the elimination half-life obtained after the single dose and after the two repeated dose regimens studied. This finding suggests that HTB displays a linear pharmacokinetic behaviour. PMID- 2272717 TI - Effect of intravesical instillation of varying doses of verapamil (20 mg, 40 mg, 80 mg) upon urinary bladder function in chronic traumatic paraplegics with overactive detrusor function. AB - The effect of intravesical instillation of verapamil was studied in eight chronic, traumatic paraplegics. Cystometry was performed before and 2 h after intravesical instillation of 20 mg of verapamil. After a gap of 10 days, the study was performed with 40 mg of verapamil and after an interval of another 10 days, the effect of intravesical instillation of 80 mg of verapamil was studied. No side-effects were observed after the intravesical administration of 20 mg, 40 mg or 80 mg of verapamil. The intravesical volume at detrusor reflex activity or at first uninhibited detrusor contraction (IV-DR) showed no significant change after intravesical instillation of 20 mg; but IV-DR increased from 90 +/- 22 ml to 131 +/- 21 ml (p less than 0.001) after intravesical instillation of 40 mg of verapamil. There was a significant increase in IV-DR from 96 +/- 23 ml to 242 +/- 35 ml after intravesical instillation of 80 mg of verapamil (p less than 0.001). There was no significant change in detrusor pressure at detrusor reflex activity or at first uninhibited detrusor contraction after intravesical instillation of 20 mg, 40 mg or 80 mg of verapamil. The frequency of voiding recorded before and one day after intravesical instillation of either 20 mg or 40 mg of verapamil showed no significant change. But the frequency of voiding recorded before and one day after intravesical instillation of 80 mg of verapamil showed a significant decrease from 19 +/- 2 to 8 +/- 1 (p less than 0.001). PMID- 2272718 TI - Detection of drug interactions with single dose acenocoumarol: new screening method? AB - In this study, a design for the evaluation of drug interactions with an oral anticoagulant drug was investigated. The interaction between a single dose of acenocoumarol and cimetidine or pentobarbitone was studied. Nine healthy volunteers received three treatments: 1) 10 mg acenocoumarol in combination with cimetidine, 2) 10 mg acenocoumarol in combination with placebo, 3) 10 mg acenocoumarol after one week pretreatment with pentobarbitone. The pharmacokinetics and the pharmacodynamics of acenocoumarol were monitored for 36 h. In all subjects the plasma concentration of acenocoumarol remained consistently higher during cimetidine treatment and consistently lower after pentobarbitone pretreatment compared to placebo treatment. Cimetidine increased the anticoagulant response of acenocoumarol as measured by the Thrombotest and pentobarbitone decreased this response in all subjects. It is concluded from this study that both pharmacokinetic and pharmacodynamic drug interactions with acenocoumarol (and presumably other oral anticoagulants) can be detected after single doses, possibly obviating the use of long-term anticoagulation in healthy volunteers. PMID- 2272719 TI - The diagnosis of alcohol and cannabis dependence (addiction) in cocaine dependence (addiction). AB - In two separate studies in 263 inpatients using DSM-III-R criteria for alcohol and drug dependence (addiction) we confirm the clinical experience that cocaine addicts are dependent on other drugs including alcohol. Our study finds a high prevalence of alcohol dependence and cannabis dependence in patients with cocaine dependence. As many as 89% of cocaine addicts diagnosed by DSM-III-R criteria for cocaine dependence (addiction) qualify for other alcohol and drug dependence diagnoses. Previous reports regarding alcohol and other drug use among cocaine addicts are few and inconclusive. The diagnosis of other alcohol and drug dependence in cocaine dependence has important impact on etiology, prognosis, and treatment. PMID- 2272720 TI - Prevention of AIDS: free condoms to drug abusers in the Municipality of Copenhagen. AB - The slogan "safer sex" was presented in a questionnaire investigation carried out over an interval of 6 months among intravenous drug addicts (N = 116) attending three different outpatient clinics in Copenhagen. Despite this, many of the patients, who were mainly heterosexual and many of whom were HIV positive, continued to practice sexual and injection behaviors which exposed both them and others to HIV infection. Free condoms and advice have been offered as a part of the campaign against AIDS. The initiative was well accepted by the drug addicts and within a period of 6 months there was an increase of 19% in the group which employed condoms. It is concluded that there is still a need for initiatives and research to support the changes achieved in the behavioral pattern of the population. PMID- 2272721 TI - Differential associations and definitions: a panel study of youthful drinking behavior. AB - This article reports on a test of selected elements of social learning theory, using a panel of public school students residing in a small southwestern city. Specifically, the drinking habits of 373 middle school and 282 high school students were examined at Time 1 and Time 2, as were changes in their attitudes, orientations, and patterns of drinking. We evaluated the assertions of social learning theory's proponents concerning its processual aspects. The results were largely consistent with the principles of social learning, although the drug related messages conveyed by both parents and significant-other adults played only minor roles in the process for either group. We found support for the notion that the process of learning to drink is not uniform throughout the secondary school experience. The implications of these findings for social learning theory and drug intervention programs are addressed in this article. PMID- 2272722 TI - Effects of a school-based prevention program for potential high school dropouts and drug abusers. AB - This study tested the effects of a prevention program based on an integrated social support and psychoeducational model. A semester-long Interpersonal Relations (IPR) class was predicted to deter school drop-out problems and drug abuse among adolescents. Quasi-experimental designs were used to field test the IPR program with 264 high-risk students in one of two conditions: (1) pretest, treatment, and posttest; (2) pretest and posttest. All hypotheses were supported. Significantly more potential dropouts were retained in the treated (74%) versus the comparison group (61%); differences in daily attendance (F = 12.88) and GPA, school achievement (F = 16.89), were significantly better in the treatment group (p less than .0001); drug involvement declined significantly from pre- to posttreatment for IPR program participants (t = 4.61, p less than .0001). Implications for treatment and recommendations for future research are discussed. PMID- 2272724 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2272723 TI - Problem drinking and obesity: a comparison in personality patterns and life style. AB - Problem drinkers attending an outpatient alcoholism program and obese clients attending an outpatient weight program were compared with each other and with matched control groups on life-style characteristics and personality variables (Adjective Check List). While both treatment groups expressed high dissatisfaction with all aspects of their lives, relative to controls, problem drinkers experienced a greater variety of problems than weight clients. Problem drinkers and weight clients were both significantly differentiated from their respective control groups on 10 of 24 Adjective Check List scales. Moreover, the two treatment groups showed substantial similarity in overall personality profiles. Both groups indicated characteristics of impulsivity, dependency, and self-abasement. Problem drinkers uniquely showed high drive and unconventionality, whereas weight clients uniquely showed submissiveness and low ambition. PMID- 2272725 TI - Interleukin-2 increases the oxidative activity and induces migration of murine polymorphonuclear leukocytes in vivo. AB - Since recombinant human interleukin-2 (IL-2) can protect mice from a lethal bacterial challenge and can induce a vascular leak, we investigated the effects of IL-2 on the oxidative metabolism and migration of murine polymorphonuclear leukocytes (PMN) in vivo. To assess oxidative activity of PMN, we used luminol dependent chemiluminescence (CL) to measure oxygen radical formation after stimulation of the PMN with phorbol myristate acetate (PMA). We demonstrated that single IP doses of IL-2, from 0.2-3 mg/kg, could significantly increase CL from peripheral blood PMN obtained after IL-2 treatment. The increase of PMN-CL induced by IL-2 in vivo reached a maximum 4.5 fold increase at 3 and 6 h after IL 2 treatment. At 1, 12, and 24 h after rIL-2 treatment, there were no changes in CL and PMN activity remained within normal limits. Intraperitoneally administered IL-2 also caused a significant influx of PMN into the peritoneal cavity. IL-2 increased the percentage of PMN among the peritoneal exudate cells from a control baseline level of less than 1% to 18% PMN after IL-2 treatment. These data that demonstrate the capacity of IL-2 to augment the function and metabolism of PMN in vivo and illustrates the broad range of effects of IL-2 on the immune system in vivo and may explain in part the protective effects of IL-2 in experimental bacterial infections and the possible role of PMN in the systemic toxicities induced by IL-2. PMID- 2272726 TI - Induction of endogenous lymphokine-activated killer activity by combined administration of lentinan and interleukin 2. AB - Lymphokine-activated killer activity in vivo (endogenous LAK activity) was found to be augmented by combined administration of lentinan, a beta (1-3) glucan with beta-1,6 branches, and interleukin 2 (IL-2). In contrast, addition of lentinan during culture in vitro did not augment LAK activity induced by IL-2. Surface marker analysis of endogenous LAK cells revealed that endogenous LAK cells induced by a combined administration of lentinan and IL-2 were all NK-type LAK cells, which express asialo-GM1 and lack T3, Thy-1 and Lyt2, whereas LAK cells generated in vitro were composed of both NK-type LAK and T-type LAK cells, which express T3 and Thy-1, and lack asialo-GM1. Furthermore, combined administration of lentinan and IL-2 was found to augment the endogenous LAK activity even in the tumor bearer, and show a substantial inhibition of tumor growth and a significant increase in survival rate in the C3H/HeN/MM46 system. Results of the present investigation offer a possible clinical application of a combination of lentinan and IL-2 for immunotherapy against cancer without detrimental side effects. PMID- 2272727 TI - Immunopharmacological properties of a protein-bound histamine metabolite. AB - Histamine metabolite was prepared by incubating histamine dihydrochloride and diamino oxidase for 24 h at 37 degrees C. Radioactive histamine was used for monitoring the whole procedure and to select the best experimental protocol. Pharmacological activities of histamine are abolished by this procedure. Histamine metabolite was found to bind to the serum proteins, to inhibit the PHA response of mouse and human mononuclear cells and to accelerate mortality rates in tumor-bearing mice. Thin layer chromatography allowed separation of metabolite from histamine and from known imidazol-derived compounds. This is the first experimental evidence for immunological properties ascribed to a histamine metabolite. PMID- 2272728 TI - Inhibition of phytohemagglutinin-induced lymphocyte proliferation by dexamethasone: mechanisms of individual susceptibility. AB - Direct positive correlation has been shown between the level of stimulation of peripheral blood lymphocytes and of the inhibition degree of PHA stimulation by dexamethasone. On the basis of this correlation we subdivided all the examined individuals into three groups of susceptibility: resistant, sensitive, and intermediate. The studies carried out in these groups showed that the reception effectiveness of glucocorticoids (GC) was much higher in the sensitive group than in the group of resistant individuals. In this group interleukin 2 (IL-2) production was relatively high; in the intermediate group this parameter was lower, and in the group of sensitive individuals the mean indices of IL-2 production were the lowest. However, this latter group unlike the two others was heterogeneous and may be divided into two subgroups: high and low IL-2 producers. HLA antigens B7 and DR2 were also shown to be associated with a decrease in sensitivity to GC inhibition of PHA-induced lymphocyte proliferation. Our results indicate that the method we used is adequate enough for dividing individuals into sensitivity groups. PMID- 2272729 TI - Immunosuppressive activity of 4'-iodo-4'-deoxy-doxorubicin on humoral and cell mediated immune responses in mice: comparison with doxorubicin. AB - 4'-Iodo-4'-deoxy-doxorubicin (I-DX) is a new halogenated doxorubicin (DX) derivative, selected for clinical testing in view of a number of pharmacotoxicological advantages vis-a-vis the parental compound. It was thus of interest to compare the immunological effects of I-DX to those of DX. The compounds were injected i.v. into mice at equal doses in terms of acute toxicity, over a variety of treatment schedules. When tested in single doses for anti SRBC primary and secondary antibody response, I-DX, unlike DX, was not immunodepressive; on the contrary it often caused a moderate amplification of the response. Following a multiple treatment schedule, I-DX was as depressive as DX only when administered after the antigen, any other treatment regimen, before or concomitant with the antigen, being uneffective. I-DX was completely uneffective and DX only slightly active in delaying skin allograft rejection and in reducing DTH reactivity to SRBC. I-DX was more inhibitory than DX for lymphoid cells in vitro, and both drugs reduced spleen cellularity without modifying the relative percentage of B and T cells after administration in vivo. However, the splenic reactivity to LPS ex vivo, unlike that to ConA, was restored earlier in I-DX than in DX-treated mice. PMID- 2272730 TI - Effect of orally administered beta-glucan on macrophage function in mice. AB - The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on the function of peritoneal macrophages in CDF1 mice was examined. Oral administration of SSG (20, 40, 80 or 160 mg/kg, daily for 10 consecutive days) enhanced the acid phosphatase activity of peritoneal macrophages. The greatest enhancing effect was observed at 80 mg/kg of SSG. Relatively long periods of administration (more than 10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity, candidacidal activity, hydrogen peroxide (H2O2) production and interleukin-1 (IL-1) production of peritoneal macrophages were also enhanced after the administration of SSG by the oral route (80 or 160 mg/kg). However, the durations of the activated state after completion of administration differed depending on the activity. Enhanced activity of lysosomal enzyme (acid phosphatase) was also shown in peritoneal macrophages taken from C3H/HeJ mice, which is a nonresponder strain to bacterial lipopolysaccharide (LPS). These results demonstrate that SSG given by the oral route can activate peritoneal macrophages in mice. PMID- 2272731 TI - Immunotoxicity testing in the rat: an improved multiple assay model. AB - Improvements have been made in the multiple assay model for assessing immunotoxicity in the rat which were previously reported (Exon, J.H., Koller, L.D., Talcott, P.A., O'Reilly, C.A. & Henningsen, G.M. (1986). Immunotoxicity testing: an economical multiple-assay approach. Fund. appl. Toxic., 7, 387-397). This improved model differs from the original in that: (1) the use of Freund's adjuvant has been eliminated from the antigen treatment schedule; (2) the same antigen, keyhole limpet hemocyanin (KLH), is used to induce both the delayed-type hypersensitivity (DTH) and specific antibody responses instead of separate antigens for each; and (3) the timing of antigen injections have been adjusted so that the DTH response is measured at the same time other assays are performed. These modifications have thus reduced the chance of non-specific stimulation of the immune system by Freund's adjuvant and eliminated possible antigen competition by using a single antigen to induce antibody synthesis and a DTH reaction. In addition, all immunoassays, including the DTH reaction, are performed at the same time, which allows for better comparison between responses and improves application to short-term repeated dose studies. Also, the immune parameters measured were shown to be sensitive to known immunosuppressants, cyclophosphamide and dexamethasone. PMID- 2272732 TI - A pathogenetic approach to the management of systemic sclerosis (scleroderma). PMID- 2272733 TI - Keratinocyte intracellular adhesion molecule-1 (ICAM-1) in the pathogenesis of Sezary syndrome and cutaneous T cell lymphoma. PMID- 2272734 TI - Parasitology and medical and veterinary sciences at the Natural History Museum, London. PMID- 2272735 TI - Regional dermatoses in the African race. Papular lesions on the face. AB - Many diseases are peculiar to the black race and most practicing physicians in Africa have limited access to histopathologists, therefore, diagnosis is largely clinical. A retrospective study of 10,000 consecutive patients seen at the skin clinic of the Lagos University Teaching Hospital, Nigeria, was conducted with the objective of identifying the notable dermatoses affecting various parts of the body. The face and the shins were observed to have a very broad spectrum of dermatoses. Useful clinical descriptions of these dermatoses are highlighted in a three part paper to help practicing physicians. PMID- 2272736 TI - Subungual leukemia cutis. AB - A 79-year-old man had generalized humping of the nails and subungual tumors involving several fingers and the left big toe. Findings on histologic study of the tumor, together with the pattern on the peripheral blood smear, established the diagnosis of chronic lymphocytic leukemia. To the best of our knowledge, this is the first reported case of chronic lymphocytic leukemia involving the subungual area. The authors' observation emphasizes the importance of taking a biopsy specimen in the differential diagnosis of subungual tumors. PMID- 2272737 TI - Psoriasis patient support group and self-care efficacy as an adjunct to day care center treatment. AB - Patients treated with chronic disabling psoriasis often have psychosocial concerns that need to be addressed. The weekly patient support group at Stanford, led by a psychiatrist, is an integral part of the Psoriasis Day Care program. Although not considered group therapy in the traditional sense due to its self selective nature, the support group aims to reduce feelings of isolation and to enhance coping skills and self-efficacy. In this setting, patients explore their feelings about psoriasis enabling them to better adapt to a visible disease. Common topics for discussion include lifestyle changes, stressful relationships, associated emotional reactions, occupational limitations, and treatment concerns. Components of the Psoriasis Day Care Center that enhance treatment response and responsibility for self-care include: health education, psychosocial support systems, stress reduction, and enhanced coping skills acquired through shared experiences with other patients and medical personnel. PMID- 2272739 TI - Elastosis perforans serpiginosa: treatment with liquid nitrogen. PMID- 2272738 TI - Chronic lymphocytic leukemia and cutaneous granulomas at sites of herpes zoster scars. PMID- 2272740 TI - Lumpy scalp syndrome. PMID- 2272741 TI - The history of cutaneous tuberculosis. PMID- 2272742 TI - Metastasis of an untreated thin melanoma in a very elderly patient. PMID- 2272743 TI - Telogen effluvium associated with albendazole therapy. PMID- 2272744 TI - Imported cutaneous leishmaniasis in Japan. PMID- 2272745 TI - Directorship at New York skin and cancer in 1947. PMID- 2272747 TI - Isolation and structure elucidation of bovine pineal arginine vasopressin: arginine vasotocin not identified. AB - A large number of reports have demonstrated the presence of neurohypophysial hormone-like peptides in mammalian pineal glands and an antigonadotropic function has been ascribed to pineal arginine vasotocin (AVT). We have undertaken large scale purification of bovine pineal neurohypophysial hormone-like substances which demonstrate mouse mammary milk-ejection activity (ME-activity) in vitro. Peptides with ME-activity were extracted from more than 5 kg of bovine pineal glands. ME-activity containing peptides were found in both high (Mr approximately 10,000-15,000) and low (Mr approximately 500-1000) Mr species from Sephadex G-25 chromatography of 0.2 N acetic acid extracts. After ultrafiltration in 5% formic acid, the neurohypophysial hormone-like peptides were localized to an ultrafiltration Mr 500-1000 retentate. A homogeneous peptide, which shared an identical retention time (RT) and amino acid sequence with synthetic 8-arginine vasopressin (AVP), was isolated by serial semipreparative high performance liquid chromatography. On the other hand, the non-mammalian nonapeptide AVT was not identified. PMID- 2272746 TI - Synthesis of a cyclic hexapeptide with sequence corresponding to murine tumor necrosis factor-(127-132) as a novel potential antitumor agent. AB - A cyclic hexapeptide cyclo(Lys-Gly-Asp-Gln-Leu-Ser-) 10 was synthesized stepwise in solution by acylation of peptide ester trifluoroacetates directly with preactivated Boc-amino acids using the DCC/HOBt method; the final cyclization reaction was performed using the pentafluorophenyl ester method in solution (1 4). This peptide is a cyclic derivative of murine tumor necrosis factor-(127-132) and is designed as a potential antitumor agent. The cyclic peptide 10 displayed weak cytotoxic activity on three of the four human tumor cell lines tested. PMID- 2272748 TI - Conformation of a cyclic decapeptide analog of a repeat pentapeptide sequence of elastin: cyclo-bis(valyl-prolyl-alanyl-valyl-glycyl). AB - The conformation of a cyclic decapeptide analog of a repeat sequence of elastin has been determined in the crystalline state using X-ray crystallographic techniques. Tetragonal crystals were grown from a solution of the decapeptide in water; space group P4(2)2(1)2, a = 19.439(2) & c = 13.602(1) A, with four formula units (C40H66N10O10.4H2O) per unit cell. The cyclic decapeptide in the crystal exhibits exact twofold symmetry. The asymmetric unit contains one pentapeptide and two water molecules for a total of 32 nonhydrogen atoms. The structure has been determined by the application of direct methods and refined by full-matrix least squares to an R index of 0.053 for 2272 reflections with intensities greater than 2 sigma(I). The backbone conformation of the asymmetric pentapeptide can be described as consisting of a double beta bend of Type III-I. The Type III turn has Pro (phi = -59.3 degrees, psi = -26.8 degrees) and Ala (phi = -65.9 degrees, psi = -23.1 degrees) at the corners while Type I turn has Ala (phi = 65.9 degrees, psi = -23.1 degrees) and Val (phi = -98.9 degrees, psi = 8.3 degrees) as the corner residues. The cyclic decapeptide has two such double bends linked together by Gly-Val bridges. PMID- 2272749 TI - Proposed solution structure of endothelin. AB - A model is proposed for the 3-dimensional structure of endothelin, a potent vasoconstrictor and pressor peptide from vascular endothelium. The model is derived through protein structure prediction and circular dichroism studies, and is based on the atomic coordinates for the bee-venom peptide apamin. The model derived shows the same turn-helix motif as observed for apamin and mast-cell degranulating peptide. On the basis of this model we suggest possible strategies for endothelin antagonist design, and note that this motif may be common in a number of peptides acting on channel proteins. PMID- 2272750 TI - Synthesis of glutathione analogues with modified ionizable groups for the study of enzyme:ligand interactions. AB - The syntheses and analyses of GSSG analogues with modified ionizable groups are described. Using the mixed anhydride method, three symmetrical and three asymmetrical peptide analogues were obtained in moderate overall yields. The products were analyzed by HPLC, 1H-NMR, thin-layer electrophoresis, and amino acid analysis. They were used to study enzyme:ligand interactions in glutathione reductase. PMID- 2272751 TI - Conformations of disulfide bridges in proteins. AB - The conformational characteristics of disulfide bridges in proteins have been analyzed using a dataset of 22 protein structures, available at a resolution of less than or equal to 2.0 A, containing a total of 72 disulfide crosslinks. The parameters used in the analysis include (phi, psi) values at Cys residues, bridge dihedral angles chi ss, chi i1, chi j1, chi i2, and chi j2, the distances C alpha i-C alpha j and C beta i-C beta j between the C alpha and C beta atoms of Cys(i) and Cys(j). Eight families of bridge conformations with three or more occurrences have been identified on the basis of these stereochemical parameters. The most populated family corresponds to the "left handed spiral" identified earlier by Richardson [1981) Adv. Protein Chem. 34, 167-330). Disulfide bridging across antiparallel extended strands is observed in alpha-lytic protease, crambin, and beta-trypsin and this structure is shown to be very similar to those obtained in small cystine peptides. Solvent accessible surface area calculations show that the overwhelming majority of disulfide bridges are inaccessible to solvent. PMID- 2272752 TI - Structure of the fibrinogen binding sequence: arginylglycylaspartic acid (RGD). AB - The crystal structure of a tetrahydrated form of L-arginyl-glycyl-L-aspartic acid (RGD), the consensus sequence for binding of fibrinogen to cell surface receptors, has been determined from diffractometer data. The tripeptide was crystallized in double zwitterionic form via hanging drop vapor diffusion experiments at a pH near 6.5. The orthorhombic unit cell contains four formula units in space group P2(1)2(1)2(1) with lattice parameters a = 4.852(4), b = 11.376(3), c = 34.083(8)A at RT. The structure was solved by direct methods and refined to a final R = 0.067 based upon 1345 observations with I greater than or equal to 2 sigma(I). Peptide bonds both are trans, omega 2 = 174.2(6) degrees and omega 3 = -169.3(6) degrees. The backbone bends at glycine with phi 2 = -85.5(8) degrees. One of the water molecules sits between the arginyl side chain and the C terminal carboxylate, forming an intramolecular hydrogen bond to the glycyl carboxyl and linking adjacent molecules through two other H-bond interactions. Comparison of the structure to RGD sequences extracted from 3-D protein structures reveals a diversity of conformations for this tripeptide sequence. PMID- 2272753 TI - Intramolecular H-bonds and thioamide rotational isomerism in thiopeptides. AB - Mono- and dithionated N-acyl amino acid and dipeptide N'-methylamides were synthesized using Lawesson's reagent and S-thioacetyl thioglycolic acid. The conformation of the thionated models was characterized by IR, 13C, and 1H NMR spectroscopy, including NOE experiments. The formation of -C = S...H-N-C = X (X = O or S) intramolecular H-bonds of the type 2----2, 1----3 and 1----4 was evidenced by the characteristic shifts of the IR stretching frequencies of the NH group. Act-Pro-NHCH3(4) and Act-Prot-NHCH3(5) were found to be present as mixtures of rotational isomers about the CS-N bond. 13C chemical shifts of the gamma- and beta-carbons of the proline ring elucidated the conformation (Z or E) of the tertiary thioamide group. Our results suggest that the conformation of thiopeptides is determined by two factors: 1) the H-bond donating and accepting ability of the thioamide group and 2) the repulsion between the thiocarbonyl sulfur atom and the side chain groups of the neighbouring amino acid residues. PMID- 2272755 TI - Isolation, identification, and characterization of a palladium complex in the catalytic deprotection of a protected peptide. AB - The final catalytic deprotection in the large scale synthesis of thymopentin (Arg Lys-Asp-Val-Tyr) produced an impurity which had not previously been observed. Isolation by preparative HPLC and spectroscopic characterization led to a postulated structure of the impurity as the 1:1 thymopentin-palladium complex. A complex corresponding to the proposed structure was independently synthesized and shown to have identical chromatographic and spectroscopic properties with the isolated material. Proton and carbon (13) NMR were used to determine the coordination sites of the peptide with palladium. The susceptibility of the complex to hydrogenation indicated a possible source for its formation. PMID- 2272754 TI - Acid-labile anchoring linkages for solid phase synthesis of C-terminal asparagine peptides using the Fmoc strategy. AB - Two acid-labile substituted benzylamine type anchoring linkages, 4-benzoxy-2,6 dimethoxybenzylamine and 2-benzoxy-4,6-dimethoxybenzylamine, for solid phase synthesis of peptide amides were prepared. The Na-9-fluorenylmethyloxycarbonyl (Fmoc) amino acids could be easily attached to the resins with DCC/HOBt (loading 0.5-0.6 mmol/g resin). After final removal of the Na-protecting groups, treatment with TFA (50-95%) yielded amino acid and peptide amides in high purity. As we could show for the synthesis of thymulin (FTS, pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser Asn), these two resins with anchoring linkages are well suited for the synthesis of C-terminal Asn peptides using protected aspartic acid derivative as starting material. PMID- 2272756 TI - An improved solid-phase synthesis of a difficult-sequence peptide using hexafluoro-2-propanol. PMID- 2272757 TI - A facile method for preparation of t-butyloxycarbonylamino acid p-nitroanilides. AB - A series of p-nitroanilides of t-butyloxycarbonylamino acids, including Boc-Trp, Boc-Asn, Boc-Gln, Boc-Ser(But), Boc-Thr(But), Boc-Asp(OBut), Boc-Lys(TFA), and Boc-His(Boc), were prepared conveniently by the mixed anhydride method using 2,2 dimethylpropanoic chloride (pivaloyl chloride). The products were obtained in 40 60% yields after purification by column chromatography on Sephadex LH-20. p Nitroanilide of histidine was purified after deprotection of Boc-His(Boc)-pNA and obtained as H-His-pNA.2HCl. PMID- 2272758 TI - Synthesis of oligophosphoseryl sequences occurring in casein. Identification of beta-elimination during phosphorylation. AB - The protected oligophosphoseryl peptides from bovine caseins, Z-Xxx (Ser[PO(OPh)2])3-Glu(OBzl)-OBzl for Xxx = Ile, Val, Gly, Leu and Ph = phenyl, were synthesized in high yields by stepwise lengthening using Boc-Ser[PO(OPh)2] OH as acylating carboxyl component and N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling reagent. The hydrogenolytic deprotection (PtO2) was carried out with the valine derivative and with the tetrapeptide Ser[PO(OPh)2]3-Glu(OBz)-OBzl. Phosphorylation of oligoseryl peptides failed to give the expected products. Large scale phosphorylation of protected serine was carried out in the presence of triethylamine using absolute ether as a solvent. 2,2,2-Trichloroethyl group (Tc) was shown to be a useful phosphorus protecting moiety in phosphopeptide synthesis: Boc-Ser[PO(OTc)2]-OBzl, Z-Ser[PO(OTc)2]-OBzl and Boc-Glu(OBzl)-Ser[PO(OTc)2]-OBzl were synthesized in high yields using bis (2,2,2-trichloroethyl) phosphochloridate. PMID- 2272760 TI - [Features and functions of environmental epidemiology]. AB - The interest of epidemiology in the environmental effects has grown up in recent years. The present paper discusses the role of environmental epidemiology based on a revision of the medical literature appeared in 1989, and on a review of the strategy in setting up standards. Different aspects of the exposure measure, the main characteristic of environmental epidemiology are presented. PMID- 2272759 TI - [Detection of alcohol-related problems in primary care]. AB - The results of a survey of primary health care physicians in order to know which factors are associated with the efficacy in the detection and treatment of patients with alcohol-related problems are analyzed in this article. The number of diagnosed patients is related with previous formal education on alcohol related problems of primary health care physicians. Primary health care physicians are very interested in this issue, but they don't feel satisfied nor gratified with their work with this type of patients. Gratifying feelings are directly related to previous formal education, and those who feel gratified diagnose more patients. Needs for formal education must be accompanied by profound organizational changes in the coordination of actions between primary health care, specialized services and social care. PMID- 2272761 TI - [Changes necessary for continuing health reform: I. The "external" change]. AB - The article analyzes the need to obtain support from all actors if the reform of the health system is to be finalized. The relevant groups are the government, professional groups, workers, the population, civil servants, managers and firms with interests in the health field. It is necessary to develop a social marketing strategy that reinforces and broadens the current supports to change. Basic elements would be: Develop new service to satisfy users' needs; orient the services to defined "market" segments; position new services or "re-position" the existing ones in order to communicate their advantages; develop a plan of marketing based on promotion, prize and place focused on the role of health professionals as the main service sellers. PMID- 2272762 TI - [Changes necessary for continuing health reform: II. The "internal" change]. AB - The article desired organizational and managerial changes in Primary Health Care, so as to develop a sound and feasible social marketing strategy. Key elements that should be changed are: 1. Rigid and centralized administrative structures and procedures. 2. Incentives system centralized and dissociated from the managerial structure. 3. Primary Health Care management units immersed in political conflict. 4. Absence of alternative in the margin. Users cannot choose. 5. Lack of an internal marketing strategy. Several ways of internal markets simulation are assessed as potential means for internal change. The need for an administration reform leading to a less inflexible system in the Spanish national and regional health services in reviewed too. Three changes are considered essential: a) Payment systems in Primary Health Care. b) Modifications in the personnel contracts. c) Reform of the budgeting processes. Specific strategies in each of these issues are suggested, making emphasizing the need of their interrelationship and coherence. PMID- 2272763 TI - [Opinion on abortion among medical students]. PMID- 2272764 TI - [Use of a consensus method for determining the health needs in Elche]. PMID- 2272765 TI - Automated measurement of transplantable solid tumors using digital electronic calipers interfaced to a microcomputer. AB - Data collection for transplantable solid tumors has been automated with electronic digital calipers and a balance which have been coupled through an RS 232 interface to a microcomputer. BASIC programs handle data entry, calculations and data storage. A "PROTOCOL" program accepts keyboard input of sample name, notebook number, submitter and dose along with necessary information on tumor system, and then initial animal weights for treatment groups are sent from balance to computer. Data is stored as an ASCII file on floppy disks, and protocol reports are printed. When the test is to be measured, a "MEASURE" program prompts the user for keyboard entry of toxic deaths in each group. Then the computer requests input of width and length of tumors for each animal. These tumor dimensions are sent to microcomputer by pressing a button on the calipers. When a group is completed, final animal weights are sent from balance to microcomputer. Then tumor weights and percent inhibition as compared to appropriate control groups are calculated, and the data is appended to the file for that test. A hard copy is generated as tumors are measured, and reports including percent inhibition can be printed immediately after a test is measured. The data as an ASCII file is transferred via modem to mainframe computer, where another program transfers the information to a database management program. These automated procedures for tumor measurement save time and lessen the chance for error by eliminating manual recording of solid tumor dimensions and subsequent reentry of this data for calculation. PMID- 2272766 TI - Combination of flavone acetic acid (FAA) with adriamycin, cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells. AB - Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethylornithine (DFMO)--an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific. PMID- 2272767 TI - Phase I trial of intravenous vinzolidine (LY 104208) given on a biweekly dosing schedule. AB - Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5-14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14-15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study. PMID- 2272768 TI - Phase I study of idarubicin administered orally on a daily x 3 schedule. AB - Twenty-one adult patients with refractory solid tumors were treated on a phase I study of idarubicin (4-demethoxydaunorubicin) administered daily for 3 days every 3 weeks. Nineteen of the patients had received previous chemotherapy (including 13 with prior anthracyclines), and 12 had received prior radiotherapy. Idarubicin dose levels of 10, 15, 17.5, 20, and 25 mg/m2 were explored. Hematological toxicity was dose-related. Other toxicity was acceptable. Only one patient (treated with an idarubicin dose of 17.5 mg/m2/day) developed neutropenic fever, from which he recovered. Further dose escalations beyond 25 mg/m2 were not carried out because of the increasing length of time required for recovery from granulocytopenia at higher doses. No patient experienced a major response, but minor responses were seen in 3 patients with carcinomas of the colon, breast, and kidney respectively. Further phase II studies of oral idarubicin at a starting dose of 20-25 mg/m2 daily times 3 days in patients with good bone marrow reserves are recommended. Because of the degree of neutropenia expected, patients would have to be observed carefully. PMID- 2272769 TI - A phase II study of mitoxantrone in advanced gastric cancer. AB - Sixteen patients with advanced adenocarcinoma of the stomach were entered into a phase II study of mitoxantrone at a dosage of either 12 mg/m2 or 14 mg/m2 given at 3 weekly intervals. Nine patients had received prior chemotherapy including doxorubicin. No patients achieved either a complete or partial response, five patients had stable disease and the remainder disease progression. Moderate to severe leukopenia occurred in 10 patients with one septic death. Median survival for all patients was eight weeks (range 1-49 weeks). It is concluded that mitoxantrone has no worthwhile activity in gastric cancer at the described doses. PMID- 2272770 TI - A phase II trial of echinomycin in metastatic cervix carcinoma. PMID- 2272771 TI - Bisantrene in advanced, hormone-resistant carcinoma of the prostate: an Illinois Cancer Council phase II study. PMID- 2272772 TI - Phase II trial of carboplatin and vinblastine in adenocarcinoma of the stomach. AB - Twenty-five previously untreated patients with advanced adenocarcinoma of the upper gastrointestinal tract were treated with a combination of carboplatin and vinblastine. Two partial responses (duration three months and six months) were seen among 22 evaluable patients. Myelosuppression was the most common toxicity and was generally mild. The 8% response rate, (95% confidence interval 2 to 24%) observed in this study indicated that carboplatin-vinblastine has only modest activity in adenocarcinoma of the upper gastrointestinal tract. Although less toxic, this regimen appears to be less effective than previously reported cisplatin-containing regimens in adenocarcinoma of the upper GI tract. PMID- 2272773 TI - Esorubicin (deoxydoxorubicin) has low grade activity in malignant melanoma. Results of an Eastern Cooperative Oncology Group study (EST 2685). AB - In this phase II trial, twenty patients with advanced, measurable melanoma from ECOG institutions were treated with esorubicin 30 mg/m2 iv every three weeks. Doses were escalated or reduced based on nadir counts. The dose limiting toxicity was leukopenia with no significant thrombocytopenia or anemia. Other toxicities were mild. One patient had skin necrosis with extravasation. Two patients with soft tissue disease had partial remissions and were treated with 9 and 17 courses. One patient was stable for 8 courses. No cardiac toxicity was seen in three patients receiving more than 150 mg/m2. The response rate was 10% (90% CI = 2 to 30%). Low level activity was seen, but it is unlikely that this drug has sufficient activity to warrant further development in melanoma. PMID- 2272775 TI - Virus species, a much overlooked but essential concept in virus classification. PMID- 2272774 TI - Phase II study of esorubicin (4'deoxydoxorubicin) in anthracycline naive patients with ovarian cancer. AB - Sixteen patients with metastatic ovarian cancer who had not previously been treated with anthracyclines were treated with 4'deoxydoxorubicin at a dose of 30 mg/m2 intravenously every 3 weeks. There were no clinical responses in this group of patients. Toxicities were infrequent with neutropenia and thrombocytopenia being dose limiting. Nausea and vomiting occurred in only 4 patients. We conclude that 4'deoxydoxorubicin is an inactive drug in this patient population and does not warrant further investigation in this disease. PMID- 2272776 TI - Cloning and expression of packaging gene 3 of Salmonella phage P22. AB - Packaging genes 3 of Salmonella phage P22 wild type and two mutants with altered packaging properties (HT12/4 and NT1/1) have been cloned in an expression vector. By plasmid transduction, it has been shown that the amino terminus of gene 3 is not functional in DNA packaging when fused with the Escherichia coli lacZ gene. The reconstituted genes 3, however, express functional gp3. The transduction experiments also have shown that the pac signal, which is part of gene 3, is intact in all three phages. Expression of gene product gp3 has been demonstrated in the minicell system. PMID- 2272779 TI - MPTP induced parkinsonian syndrome: long term follow-up and neurophysiological study. PMID- 2272778 TI - Usefulness and significance of the concept of leukoaraiosis in the study of dementia. PMID- 2272777 TI - Modulation of hormone secretion in vitro by murine retrovirus. AB - In an attempt to elucidate the role of viruses in certain neuroendocrine disorders, we have demonstrated that infection of endocrine cells (GH-3 and Y-1) in vitro by moloney murine leukemia virus (M-MuLV) resulted in diminution of cell specific secretory function, hormone secretion into culture. In GH-3 (rat anterior pituitary gland) active (initial) and persistent infection by M-MuLV resulted in approximately 80% reduction in prolactin and growth hormone secretion. The adrenal cortex tumor cell line (Y-1), when actively infected with the same virus, showed a transient increase in fluorogenic steroid secretion; however, on subsequent passages of infected cell cultures, steroid secretion was markedly reduced to about 10% of the uninfected Y-1 cells. The virus yield from M MuLV-infected cultures of Y-1 and GH-3 cells produced a significantly lower amount of virus than the control NIH-3T3-infected cell cultures. PMID- 2272780 TI - Cerebral blood flow and plasma volume during hyperglycemia in the conscious rat. AB - Cerebral blood flow (CBF) and cerebral plasma volume (CPV) were measured under steady-state hyperglycemic conditions in the hemispheres and brainstem-cerebellum of conscious rats. There groups of hyperglycemic animals each having a different level of plasma glucose concentration, 25, 33.3, 44.4 mmol/l, and a normoglycemic control group were studied. CBF was not affected at the hyperglycemic levels of 25 and 33.3 mmol/l. Mean hemispheric and brainstem-cerebellum CBF values appeared lower than in controls at the highest glycemic level although the differences were not statistically significant. CPV was found to be unchanged at the hyperglycemic level of 25 mmol/l, while it was found to be increased in the hemispheres of the animals whose plasma glucose concentration had been elevated to 33.3 and 44.4 mmol/l. The results of the study do not support the claim that hyperglycemia may enhance ischemic brain injury by reducing CBF. PMID- 2272781 TI - Psychopathological aspects and emotional behavior in right brain-damaged patients. AB - We investigated 20 right brain-damaged (RBD) patients and 10 controls with chronic motor deficits for differences in anxiety and depression, measured by psychometric tests, and in aspects of emotional behavior, gauged from videorecordings. We found no group differences in the psychometric scores but, when we correlated these with the behavior scores, we found significant differences in the expression of depression (absent only in RBD patients) and in attitude to illness, ie joking and unconcern (present only in RBD patients). In both groups emotional gesture, facial expression and prosody proved on qualitative analysis to be interrelated, thus demonstrating that emotional behavior has a single cortical-subcortical substrate. PMID- 2272782 TI - Hereditary motor and sensory neuropathy type I and type II. AB - In an attempt to clearly identify the different HMSN subgroups, we prospectively evaluated 128 subjects (46 index cases, 39 affected and 43 unaffected relatives) on clinical, genetic and electrophysiological grounds. The diagnosis of HMNS I or II was made in 77 patients. Differential diagnosis between type I and II patients was impossible on clinical grounds alone, but nerve conduction study showed a clear-cut subdivision into two populations. MCV behavior was consistent within families. Inheritance, autosomal dominant in almost all cases, was probably recessive in three HMSN I subjects and pedigree analysis pointed to X-linked transmission in one HMSN I family. We found no evidence for linkage to Duffy locus. We think that similar HMSN phenotypes can be determined by different gene defects. Ulnar nerve F-conduction velocity did not significantly differ from distal MCV in HMSN I: the evidence of a diffuse slowing of nerve conduction supports the hypothesis of a primary myelin defect. PMID- 2272784 TI - Recurrent cranial nerve palsies, midbrain infarction and hydrocephalus due to megadolichobasilar artery. AB - A 67-year-old man presented four recurrent, alternating facial palsies, two right abducens palsies and eventually a right extrinsic third nerve palsy due to brain stem infarction in a 37-year time-span. Neuroradiological examinations showed hydrocephalus and an elongated, tortuous, ectasic basilar artery. This patient presented in his lifetime the whole clinical spectrum of the dolichoectasic basilar artery complications. PMID- 2272783 TI - Multimodality evoked potentials in HIV infected subjects: a longitudinal study. AB - 18 subjects with symptomless HIV infection were investigated with multimodal evoked potentials for possible CNS involvement and again after an 8-12 month interval. 13 subjects showed neuropsychological changes, which were confirmed at the second examination. The 5 subjects found normal remained so at the second examination. On WAIS assessment the only patient to earn pathological scores was the one with the greatest evoked potentials changes. Thus the evoked potentials procedure proved capable of identifying early CNS involvement by HIV infection. PMID- 2272785 TI - Spontaneous subarachnoid hemorrhage in an HIV patient. AB - In an HIV-seropositive patient presenting generalized tonic-clonic seizures, magnetic resonance imaging and cerebrospinal fluid examination disclosed the signs of a previous subarachnoid bleed. No vascular malformation was observed with cerebral angiography. Laboratory tests revealed an autoimmune thrombocytopenia. A spontaneous subarachnoid hemorrhage induced by thrombocytopenia should be considered when investigating HIV patients presenting even non-specific neurological symptoms. PMID- 2272786 TI - Abnormal responses to succinylcholine and pancuronium in a patient with hemiparesis. AB - Supersensitivity to depolarization produced by succinylcholine and resistance to pancuronium were observed in paretic muscles of a patient with a right frontoparietal tumor. The abnormal sensitivity to relaxants is compared with observations reported in patients with myasthenia gravis and hemiparesis. We hypothesize that upper motoneuron dysfunction may be followed by the appearance of "new" junctional receptors, which may occasional a supersensitivity to depolarization and a poor affinity for both curare and anti-acetylcholine receptor antibodies. A decrease in acetylcholinesterase activity of "decentralized" muscles should also be considered. PMID- 2272787 TI - Giovanni Brugnoli and the origin of neuropsychology in Italy. PMID- 2272788 TI - Trigeminal sensory neuropathy and migraine: loss of headache with retention of aura. PMID- 2272789 TI - Fourth autoimmunity meeting--Noel Rose day. 25 January 1990, Tel-Hashomer, Israel. Proceedings. PMID- 2272790 TI - New autoimmune conditions. PMID- 2272791 TI - A heat shock protein, molecular mimicry and autoimmunity. PMID- 2272792 TI - Immunogenetics of HLA class II genes in primary Sjogren's syndrome in Israeli Jewish patients. PMID- 2272793 TI - Pyruvate dehydrogenase as an antigen to detect antimitochondrial antibodies. PMID- 2272794 TI - Autoimmune encephalomyelitis and the connection between the nervous and immune systems. PMID- 2272795 TI - Immunoregulation of autoimmune diseases. PMID- 2272796 TI - The importance of HLA-DR in autoimmune diseases. PMID- 2272797 TI - Anti-RA 33--a new autoantibody characteristic of rheumatoid arthritis. PMID- 2272798 TI - Is schizophrenia an autoimmune disease? PMID- 2272799 TI - Spontaneous bacterial peritonitis in alcoholic and nonalcoholic cirrhosis in southern Israel (the Negev). AB - Spontaneous bacterial peritonitis (SBP) is a syndrome diagnosed in 8-18% of hospitalized cirrhotic patients with ascites. The purpose of our study was to investigate the incidence, clinical features, treatment and mortality rate among patients in the Negev (southern Israel) during the years 1982-87. During this period, 21 patients were diagnosed, with a total of 39 episodes of SBP. While the incidence of SBP observed between 1982 and 1985 was 1.8%, this rate rose to 5.1% in 1986-87 (P less than 0.01), almost certainly a result of an increased awareness of the syndrome. Of our patients 13 had a history of nonalcoholic liver disease, while 8 others were diagnosed as having alcoholic liver disease. Nevertheless there were no significant differences regarding the clinical and laboratory features, the bacteria isolated and the outcome, between alcoholic and nonalcoholic patients, except for chills that were reported by 32% of patients with nonalcoholic liver disease and never by patients with alcoholic liver disease (P less than 0.05). We conclude that despite the fact that alcoholic cirrhosis occurs much less frequently in Israel than in Europe or North America, SBP is as frequent among hospitalized cirrhotic patients and demonstrates a similar clinical and bacteriological picture. PMID- 2272800 TI - Alopecia universalis in a patient with Marfan's syndrome. PMID- 2272801 TI - IgA deficiency in childhood: idiopathic thrombocytopenic purpura. PMID- 2272802 TI - Spontaneous bacterial peritonitis--light at the end of the tunnel. PMID- 2272803 TI - Dr. Emanuel Libman visits Palestine: an historical note. PMID- 2272804 TI - Pitfalls and pratfalls in the life of a novice editor. PMID- 2272805 TI - Do the write thing! Tips for a healthy newsletter. PMID- 2272806 TI - After the Cruzan case: uniform legislation available to help preserve rights of the terminally ill. PMID- 2272807 TI - A new approach to sinus relief. AB - You suffer from "sinus". Medical treatment isn't getting you better, and now you need surgery. It is better that you be treated surgically today rather than as in the past. Five years ago, surgery meant an incision through the eyebrow, with probable numbing of the forehead, in order to relieve the pain of acute frontal sinusitis; or a long eyebrow incision, or shaving the front part of the scalp and pulling down the forehead skin from the skull was the procedure of choice for chronic disease in these sinuses. If the cheek sinuses were chronically diseased, an incision was made through the gums above the upper teeth, often resulting in numbing of the teeth and marked swelling of the cheek. PMID- 2272808 TI - Healing places. PMID- 2272809 TI - Acute rhabdomyolysis associated with cocaine intoxication: a case report. AB - Over thirty million Americans are estimated to have tried cocaine at least once and 5 million use it on a regular basis. Recent media attention to the widespread use of cocaine has revealed the growing life-threatening complications that accompany its use. The effects of cocaine on the cardiovascular, pulmonary and central nervous system have been well-described in medical literature, but the complications of acute renal failure secondary to cocaine-induced rhabdomyolysis only recently have been addressed. Presented in this article is a case involving cocaine-induced acute renal failure. PMID- 2272810 TI - Methamphetamine in psychiatric emergencies. AB - This study examines the clinical characteristics of patients with methamphetamine induced organic mental disorders that were seen in a psychiatric emergency service. This was a highly dysfunctional group, requiring psychiatric hospitalization in 90% of cases. The most consistent clinical feature was the presence of an organic delusional syndrome, with paranoid ideation and hallucinations. Methamphetamine abusers were also unique in their propensity for violence; 43% of the group had clear histories of aggression towards others. The increasing use of methamphetamine together with its ability to produce severe dysfunction is a major concern of professionals and communities alike in terms of treatment [corrected]. PMID- 2272811 TI - Drug induced refractory headache--clinical features and management. AB - Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low tyramine, low caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that; 1.) Daily use of symptomatic or immediate relief medications result in chronic daily headache. 2.) Discontinuing daily symptomatic medications itself result in improvement of headache. 3.) Concomitant use of symptomatic medications nullifies the effect of prophylactic medications. 4.) Discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications. PMID- 2272812 TI - Acetylsalicylic acid vs. metoprolol in migraine prophylaxis--a double-blind cross over study. AB - In a double blind cross-over study, 28 patients, 5 male and 23 female, aged 31 +/ 14 years, after a run-in period of 8 weeks, were treated for 3 months with acetylsalicylic acid and for another 3 months with metoprolol, both in a prophylactic mode. Attack frequency was reduced significantly with both therapeutic regimens (ASA p less than 0.001, metoprolol p less than 0.00005). Reduction of attacks below 50% was seen with metoprolol in 14 cases, and with ASA in three cases. Even though ASA was of statistically significant efficacy in migraine prophylaxis, it clearly is not the drug of first choice in migraine prophylaxis. PMID- 2272813 TI - The VER as a diagnostic marker for childhood abdominal migraine. AB - Abdominal migraine is a common childhood migraine equivalent, for which diagnostic criteria have not been defined. As in other children with migraine equivalents this leads to difficulties in diagnosis and determination of prevalence. By recording the fast wave activity (beta rhythmn) in the visual evoked response (VER) to red and white flash, the pattern stimulation, 27 out of 28 children with clinically diagnosed abdominal migraine revealed significant differences compared with normal controls, outside the attack phase. Comparisons with children diagnosed as migraine with or without aura revealed, from the VER findings of higher amplitude fast wave activity and the presence of paroxysmal sharp wave activity, that abdominal migraine appears to be a specific form of childhood migraine. We found that both clinically and electrophysiologically, abdominal migraine changes with age; older children exhibiting a shorter duration of abdominal pain during attacks, and less evidence of sharp wave activity in the VER. PMID- 2272814 TI - 99mTc HM-PAO SPECT in pediatric migraine. AB - 99mTC HM-PAO SPECT brain imaging was performed during the headache-free period in 19 young migraineurs, affected by common migraine (CM, 10 cases), classic migraine (CLM, 6 cases) and hemiplegic migraine (HM, 3 cases). SPECT findings were negative in all 10 patients with CM, in 3 cases of CLM and in 2 cases of HM. Positive findings in the remaining 4 patients (3 cases of CLM and 1 of HM) showed a decreased tracer distribution in the temporo-occipital regions (2 cases) and parietal regions (2 cases): the two with decreased temporo-occipital perfusion reported prodromal symptoms exclusively contralateral to the areas of hypoperfusion. An impaired regional cerebral vascular autoregulation may exist even during headache-free intervals in patients suffering from classic and hemiplegic migraine. PMID- 2272815 TI - Cerebral vein thrombosis shown by MRI. AB - A 46 year old man with a short history of left facial pain and numbness, and subsequently headaches, had a normal physical examination and a normal CT scan of head. Lumbar puncture yielded normal CSF under increased pressure. MRI showed thrombosis of the superior sagittal sinus, subsequently confirmed by angiography. MRI is a sensitive test for detecting intracranial venous thrombosis, and may be the investigation of choice when this disorder is suspected. PMID- 2272816 TI - The cluster diathesis. AB - We present further evidence for a sympathetic defect of vasomotor control of the anterior cerebral artery (ACA) on the side of the headache during cluster periods. In 119 cluster headache patients, utilizing transcranial Doppler, we measured CO2 reactivity of the major intracranial vessels, in and out of cluster. Reactivity was significantly lower during the cluster period, but only in the ACA on the side of the headache. Nineteen patients followed sequentially for a full cycle (ie/both in and out of a cluster period) showed the same changes. In 3 out of 6 patients in an active cluster period, we describe a lesion on Gallium single photon emission computerized tomography (SPECT) in the region of the cavernous sinus which fades as the patient moves out of cluster. It is felt that this lesion may represent the cavernous sinus plexus lesion postulated as the central lesion in cluster. Changes in the sympathetic outflow at this point could explain the changes we have described in ACA CO2 reactivity during cluster. PMID- 2272817 TI - Cluster headache: the effect of low oxygen saturation. AB - The present study concerns the possible relationship between hypoxia and the generation of cluster headache attacks. Fifteen controls and 25 cluster headache patients were studied. The patients were allocated into two groups according to cluster headache stage, i.e. cluster or remission period. During the tests, all the subjects were asked to inhale 12% oxygen (88% N2) for 30 min, and the decreasing oxygen saturation (SaO2%) was monitored. Patients in the remission period showed nearly the same decrement of SaO2% as controls. At the end of the test, patients in the bout showed significantly less reduction of SaO2% than the controls. In 5 patients, the test was carried out both in and outside the cluster periods. The tendency to less decrement in oxygen saturation in the cluster phase was as marked with this comparison, but the difference between the groups was not significant, probably partly due to the low number of tests carried out. Only one patient got a typical attack. It seems that hypoxia of this magnitude per se is not the cause of attacks. The different pattern with respect to SaO2% following 12% O2 inhalation in cluster headache may be due to an abnormality in central regulation and/or chemoreceptor sensitivity. PMID- 2272818 TI - Relaxation training in school classes does not reduce headache complaints. AB - The effect of teacher-presented Progressive Relaxation Training (PRT) on headaches, fear of failure and school problems was studied in school students. During ten physical education lessons, students received either PRT (n = 110) or placebo training (n = 92). The effect of the training was investigated in students who indicated the presence of headaches in a pre-training diary. No significant differences were found between both training groups regarding headache frequency, duration and intensity and the psychological variables. On the basis of these and previous findings, it is recommended to present PRT to fairly small groups of self-selected subjects instead of complete classes. PMID- 2272819 TI - Recurrent tension headache in adolescents treated with self-help relaxation training and a muscle relaxant drug. AB - Forty-eight adolescents suffering from recurrent tension headache participated in a controlled trial conducted in a high school setting. During the first treatment phase self-help relaxation training was compared with a waiting-list group. Following this phase a pharmacological regimen consisting of a muscle relaxant (chlormezanone) and placebo was superimposed on relaxation therapy in a double blind crossover design. Each treatment phase encompassed a 5-week period. In addition to the evaluation of headache complaints, psychological distress among students was measured with respect to their experience of somatic complaints, depressive, anxiety and stress symptoms. Although self-help relaxation training significantly decreased the severity and annoyance of adolescents' headache besides their somatic complaints, the clinical improvement of headache was modest. The addition of chlormezanone did not help those who were nonresponders to self-help relaxation training. Finally, a set of pretreatment variables consisting of baseline headache severity and annoyance, experience of anxiety and daily life stress among adolescents could predict outcome of self-help relaxation therapy. PMID- 2272820 TI - Pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks. AB - This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/ 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml). The other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks. Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine. PMID- 2272821 TI - Challenges in the diagnosis of acute headache. PMID- 2272822 TI - Management of acute nonvascular headache: the Danish experience. PMID- 2272823 TI - Treatment of status migrainosus: the American experience. AB - Dependence upon a variety of drugs--ergotamine, analgesics, benzodiazepines, corticosteroids--is a major reason for patients to enter an intractable phase of their migrainous disorders. Repeated dosing of dihydroergotamine has proven to be remarkably effective in stabilizing the mechanism of migraine, allowing these patients to make the transition to a more reasonable as well as more specific form of therapy. PMID- 2272824 TI - [Virostatic treatment of herpes simplex infections of variable severity]. AB - Aciclovir (ACV) is the most effective drug for the virostatic management of herpes simplex virus (HSV) infections, and the rate of side-effects is low. ACV resistance is rare, occurring only in highly immunocompromised patients (so far about 30 cases have been reported). Dosages and modes of application of ACV in different HSV infections are indicated and discussed. PMID- 2272825 TI - [The psychosocial status of patients with endogenous eczema. A study using cluster analysis for the correlation of psychological factors with somatic findings]. AB - The present study was performed to investigate whether patients with atopic dermatitis differ as a group from controls on psychological measures of mood and personality or whether psychologically deviant and normal patient subgroups can be distinguished. Furthermore, we were interested in what clinical characteristics might co-vary with psychological disability in patients with atopic dermatitis. In all, 93 patients filled in a standardized mood scale (Hamburg-Erlanger-Stimmungsbarometer) and a personality scale (Kurztest zur Erfassung der Personlichkeitsstruktur). Compared with matched controls, patients described themselves as being more anxious, more aroused, more depressed and less energetic, and they reached higher neuroticism scores. A cluster analysis identified four patient subgroups. Only one of the subgroups (n = 17) was psychologically disabled according to the questionnaire scores. In contrast to a psychologically stabile patient group, the psychologically disabled patients showed an earlier age of onset of dermatitis, but less intense itching and scratching. They reported more somatic complaints and a higher level of familial stress, were more dissatisfied with their life situation and work, had fewer friends and experienced more losses of significant others. Furthermore, they more frequently rated their disorder as being determined by psychological factors and were more intelligent. Thus, the questionnaires identified a subgroup of patients who may need psychotherapeutic interventions. PMID- 2272826 TI - [Serodiagnosis in dermatological diseases in Borrelia burgdorferi infections]. AB - 185 patients with dermatological symptoms of Borrelia burgdorferi infection (erythema migrans, lymphadenosis cutis benigna, acrodermatitis chronica atrophicans) and morphea were examined for Borrelia burgdorferi antibodies; in addition, sera from 173 patients were tested for exclusion of Borrelia infection. Commercially available immunofluorescence tests and enzyme immunoassays supplied by four different companies were evaluated. To investigate the specificity of these assays, sera of 34 patients with syphilis in different stages and sera from 98 control persons were examined. None of the assays evaluated was suitable for the diagnosis of early infection (sensitivity 4-35%). However, they are more reliable for the diagnosis of late infection (sensitivity 56-100%). The variation in specificity between the different assays was 82-100%. Crossreactions with Borrelia burgdorferi antibodies occurred frequently in patients with syphilis (3 47%). The reliability of serological assays should be improved by antigen purification and combination of screening and confirmatory assays. After treatment the decline in IgG and IgM antibodies is very slow. PMID- 2272827 TI - [Metastasizing malignant melanoma from unknown primary tumor]. AB - Among a total of 1426 patients with malignant melanoma, the site of the primary tumor was unknown in 24 patients (1.7%), most of whom were male (20 of these 24 patients were male, the remaining 4, female). The average age of these 24 patients correlates with the age distribution of the 1426 patients. In half the patients under scrutiny, the first metastases were found in lymph nodes, and one quarter of these developed metastases to the brain or skin. The 21 patients it was possible to follow up over the entire period of their case history had a poor prognosis. The 5-year survival rate after excision of the first metastases was only 14%. In 8 patients the medical history indicated a previous pigmented tumour on the skin. In 4 of these patients melanophages were also found within depigmented scars located in the drainage area of the lymph nodes involved. However, there were no signs of a primary tumour either on the mucous membranes or in the eyes in any of the other patients. PMID- 2272828 TI - [Non-bullous erythroderma (congenital) ichthyosiforme with perinuclear shells]. AB - A congenital dermatosis with an unusual course is described in a 5-year-old girl. During the first months of life she was found to have erythrokeratodermatic plaques, which developed into a non-bullous (congenital) ichthyosiform erythroderma (CIE) within 1 year. Since then, the clinical picture has remained stable. Histologically, the upper epidermal layers showed ballooning and vacuolization of the keratinocytes, glycogen storage, and focal parakeratotic keratinization. Conspicuous ultrastructural alterations consisted in the formation of shells of fine-filamentous, cross-linked material of unknown nature, binuclear keratinocytes, perinuclear edema formation, and the occurrence of lipid droplets in the horny layer. The n-alkane value was within the normal range. Our histological and ultrastructural findings are largely in accordance with those in a case of "congenital reticular ichthyosiform erythroderma". The disorder seems to represent a special genotype in the heterogeneous group of the non-bullous CIEs. We suggest naming it "non-bullous (congenital) ichthyosiform erythroderma with perinuclear shells". PMID- 2272829 TI - [Colloid milium]. AB - The differential diagnosis and classification of colloid milium, a relatively rare disorder, may be difficult. In this paper, a case report of a 52-year-old male patient with characteristic clinical and histological signs of colloid milium is therefore presented. Recently gained insights into the aetiopathogenesis of colloid milium are discussed. PMID- 2272830 TI - [Post-zoster-specific skin infiltrates in chronic lymphatic leukemia]. AB - Eight weeks after suffering from herpes zoster of the right 5th cranial nerve, an 80-year-old woman with chronic lymphocytic leukaemia developed zoster-like pseudovesicular lesions in the same nerve segment. Histological and immunohistological investigations revealed specific infiltrates of chronic lymphocytic leukaemia. Chemotherapy for the underlying disease was intensified, and the cutaneous infiltrates disappeared quickly. The patient died shortly afterwards due to exacerbation of the lymphoma. PMID- 2272831 TI - [Hyalinosis cutis et mucosae (Urbach-Wiethe) in 2 sisters]. AB - The authors report on 2 sisters who had suffered from both atopic eczema and hoarseness since their birth. Rough, yellowish-white papular deposits in the skin and the oral mucosa had developed during their childhood. The clinical diagnosis of hyalinosis cutis et mucosae was confirmed in both cases by means of histology and electron microscopy. PMID- 2272832 TI - [Wound myiasis. Facultative myiasis]. AB - Two cases of traumatic myiasis, one in Bowen carcinoma and one in chronic leg ulcer, are described. The maggots isolated were reared to the adult stage; they proved to be Calliphoridae of the genus Lucilia (presumably L. sericata). The various forms of myiasis and the species involved in such parasitism are described, and the therapeutic efficiency of proteolytic enzymes and the necrolytic potency of maggots are briefly discussed. PMID- 2272833 TI - [History of dermatology in Hannover]. PMID- 2272834 TI - [On the 50th anniversary of the Linden Dermatology Hospital of the Medical University and the district capital of Hannover]. PMID- 2272835 TI - Hb J-Anatolia [alpha 61(E10)Lys----Thr]: structural characterization and gene localization of a new alpha chain variant. AB - We report the characterization of a new hemoglobin variant having a single amino acid substitution (Lys----Thr) at position 61 of the alpha chain. In addition to the structural analysis, we also describe the strategy used for the identification of the base substitution and the localization of the defect at the gene level using polymerase chain reaction and hybridization with allele-specific oligonucleotides. PMID- 2272836 TI - Hb Mizuho [beta 68(E12)Leu----Pro]. Second occurrence identified in a Caucasian child with hemolytic anemia and dense erythrocyte inclusions. AB - Hb Mizuho [beta 68(E12)Leu----Pro] was identified in a child of Italian/Sicilian descent who exhibited severe, transfusion dependent hemolytic anemia which improved following splenectomy. The patient's peripheral blood smear, which prior to splenectomy demonstrated coarse erythrocytic basophilic stippling, showed large, dense erythrocytic hemoglobin inclusions following splenectomy. Whole blood oxygen equilibrium results were consistent with the presence of a hemoglobin component exhibiting increased oxygen affinity with decreased cooperativity. The abnormal beta chain was characterized by high performance liquid chromatography analysis of the isopropanol precipitable hemoglobin fraction. PMID- 2272837 TI - Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry. AB - Hb Aalborg is a new unstable hemoglobin variant found in association with mild anemia. Heinz bodies were readily inducible in red cells but there was no specific evidence of hemolysis and the variant therefore appears to be without significant clinical effect. The amino acid replacement was identified by fast atom bombardment mass spectrometry and is that of Gly----Arg at position beta 74 (E18). Hb Aalborg is moderately unstable. PMID- 2272838 TI - Hb Johnstown [beta 109 (G11) Val----Leu]: a new electrophoretically silent variant that causes erythrocytosis. AB - A high oxygen affinity hemoglobin, previously undescribed, was found in a healthy, asymptomatic patient with mild erythrocytosis and left-shifted hemoglobin-O2 dissociation curve. The hemoglobin variant could not be distinguished from Hb A by any of several electrophoretic methods nor by ion exchange chromatography. It was separated and analyzed by reversed phase high performance liquid chromatography. Structural analysis revealed the substitution beta 109 (G11) Val----Leu. The variant was named Hb Johnstown. The amino acid substitution perhaps disrupts alpha 1 beta 1 contacts in the deoxyhemoglobin conformation, thus shifting the equilibrium towards the high affinity oxyhemoglobin conformation. PMID- 2272839 TI - Beta zero-thalassemia in a Thai family is caused by a 3.4 kb deletion including the entire beta-globin gene. AB - DNA analysis of a Northern Thai family with a child affected with beta thalassemia major revealed a novel deletion of 3.4 kb removing the entire beta globin gene in the proposita and her mother. Detailed mapping of the deletion located the 5' breakpoint in the region between nucleotides -810 and -128 of the beta-globin locus, and the 3' breakpoint between the Ava II and Xmn I sites located downstream of the beta-globin gene. The father transmitted a codon 17 nonsense mutation, a beta-thalassemia variant common in Thailand, to the child. PMID- 2272840 TI - An initiation codon mutation as a cause of a beta-thalassemia. AB - During the course of a screening program for beta-thalassemia mutations among beta-thalassemia heterozygotes in Yugoslavia we observed a mutation (ATG----ACG) in the initiation codon of the beta-globin gene which has not been described before. The abnormality was initially detected through mapping of the beta-globin gene by Southern blot analysis using the restriction enzyme Nco I. The loss of the Nco I site resulted in the presence of an 8.3 kb band in addition to the normal 5.2 kb band. The mutation was identified by sequence analysis of amplified DNA and by dot-blot analysis of this DNA with a 32P-labeled oligonucleotide probe. An additional polymorphism (CAC----CAT) was present at codon 2 on the same chromosome; this mutation was detected by Orkin et al in 1982 (1). Hematological and in vitro chain synthesis data suggest that the beta-thalassemia is of the beta zero type. PMID- 2272841 TI - Thai G gamma (A gamma delta beta)zero-thalassemia and its interaction with a single gamma-globin gene on a chromosome carrying beta zero-thalassemia. AB - Clinical manifestations and hematologic data of thalassemia intermedia were observed in three siblings of a Thai family. Analyses of the hemoglobin of their parents and other siblings indicated that they inherited a delta beta-thalassemia gene from the father and a beta zero thalassemia gene from the mother. Globin gene mapping confirmed that they carry two abnormal beta-globin gene complexes. On one chromosome more than 70 kb of DNA was removed which resulted in G gamma (A gamma delta beta)zero-thalassemia. The deletion started at the Hind III site located just 3' to the G gamma gene, and extended downstream to a region recognized by the p3'N 2.8R probe which is located more than 45 kb from the 3' end of the beta gene. The other chromosome carried a beta zero thalassemia gene, and a 5 kb deletion between the G gamma and A gamma genes which produced a hybrid -GA gamma- gene. A synthetic oligonucleotide probe showed that this beta zero thalassemia arose from a C----T mutation at position 654 of IVS-II in the beta globin gene. PMID- 2272842 TI - Hb Fukuoka [beta 2(NA2)His----Tyr]: a new mutation at the 2,3-diphosphoglycerate binding site. PMID- 2272843 TI - Hb Yamagata [beta 132(H10)Lys----Asn]: a new abnormal hemoglobin in a Japanese family. PMID- 2272844 TI - Hb Andrew-Minneapolis [beta 144(HC1)Lys----Asn] in a Bulgarian family. PMID- 2272845 TI - Finding of a bull with Y;17 translocation. AB - A bull with a Y;17 translocation was found. This finding was examined by G banding, C banding, and studying the cytodensitometric profiles of G banding. The subject appeared phenotypically normal, with normal reproductive organs and testicular function (GnRH Test). There was a slight pathospermia (oligozoospermia and asthenozoospermia), therefore the portions of Y chromosome with TDF and AZF were not lost. PMID- 2272846 TI - Heterochromatin variants in 109 ovarian cancer patients and 192 healthy subjects. AB - Aberrations of the C-band region of chromosome no. 1 (1qh) were studied in 109 patients with ovarian cancer and 192 healthy subjects. The groups were compared for heterochromatin size variations, intrapair size asymmetry, and inversion. No significant correlation was found between the size of 1qh and ovarian cancer. Heterochromatin size asymmetry was estimated visually and determined by objective measurement of 1qh length or area; the methods show strong correlation. The measurements were normalised by comparison with the length or area of 16p or the entire chromosome no. 1. However, since good reliability was found by simply relating the 1qh size difference to the mean 1qh size, this was considered an appropriate and simpler method of normalisation. Asymmetry indices of length and area measurements correlated well, implying that the simpler method of length measurements can be readily used. 1qh asymmetry, measured objectively or estimated visually, was significantly increased in the cancer patient group. The incidence of C-band inversion was significantly increased in the patient group. Moreover, inversion increased significantly with increasing 1qh asymmetry. PMID- 2272847 TI - Analysis of lymphocyte and oral mucosa cell micronuclei in Cuban paint industry workers. AB - Twenty-one workers exposed to complex mixtures in the paint industry were compared with a control group of 19 persons from a blood bank in regard to micronuclei frequency in peripheral blood lymphocytes and in oral mucosa cells. The exposed persons showed significantly increased levels of micronuclei frequencies in both types of cells. PMID- 2272848 TI - Genotypic-specific habitat selection: a new model and its application. AB - A new model of genotypic-specific habitat selection is proposed in which habitats are given a biologically meaningful way with differences in the frequency of various niches. Conditions for polymorphism are quite robust even for small viability differences. A method to estimate habitat selection parameters from information on habitat preference is given. Even when habitat preference is not great, it may have a large effect on maintaining polymorphism. PMID- 2272849 TI - Selection during a selfing programme. I. The effects of a single round of selection. AB - Theory is presented to describe the effects of a single round of selection during a selfing programme in terms of both the mean and the genetical variance of the inbred lines produced. Response equations describing the effect on the inbred means are used to determine optimum breeding designs in a limited set of circumstances. These theoretical arguments are supported by computer simulations, and good agreement with expectation is found. The magnitude and direction of dominance is shown to be unimportant even in the case of early generation selection. A description of the reduction in genetic variance between selected lines is also presented and supported by simulation. Unlike the effects described by Bulmer in outbreeding populations, this reduction is fixed during a selfing programme. The simulation studies show that the additional variance generated by further segregation after selection may also be affected by selection, but the assumption that it is unaffected is found to be adequate. PMID- 2272850 TI - Selection during a selfing programme. II. The effects of two or more rounds of selection. AB - Theory presented in a previous paper has been used to provide a description of the responses expected from selection in two or more generations of a selfing series. Optimum two-stages and multi-stage selection programmes are described, for a limited set of circumstances, and compared with the single-stage designs described previously. Simulations show that biases may be expected if epistasis is present or if the number of effective factors is small. If the number of effective factors is large, then progress from even the most efficient designs will be limited by drift. PMID- 2272851 TI - Evolution of the obscura group Drosophila species. III. Phylogenetic relationships in the subobscura cluster based on homologies of chromosome A. AB - The Drosophila subobscura cluster comprises D. subobscura, D. madeirensis and D. guanche, species closely related to some interspecific crosses are possible. This paper clarifies definitively the homologies of the segments of the sex chromosome A (= X) among these species and thus permits a phylogenetic seriation of them. This seriation is identical to the one suggested by the study of chromosome O and concordant with similar data for the remaining three rod autosomes (J, U and E), which, however, do not provide qualitative evidence on this subject. PMID- 2272852 TI - Quantitative and qualitative home assessment of primary caretaker-child interactions in lower socioeconomic families. AB - Assessment is an important component of nursing management of at-risk children. Low socioeconomic status and intrauterine growth retardation are often considered to be risk factors for developmental disabilities. Home visitation is often suggested as a way to assess adult-child interactions. In this article, the author provides information about assessments conducted in lower socioeconomic homes and difficulties encountered in conducting them. She raises several questions for consideration as a result of her efforts to assess home environments and primary caregiver-child interactions of children with intrauterine growth retardation. PMID- 2272853 TI - Value of health, incidence of depression, and level of self-esteem in low-income mothers of pre-school children. AB - Nurses are continually promoting health and healthy lifestyles. This contribution requires that nurses understand client values and priorities. Traditionally, women have had responsibility for their own and their families' health. Nurses must recognize and understand the complex influences shaping the value women place on health. The literature indicates that women want to participate actively in their own health care by assuming more responsibility for their health and well-being. This research evolved as a result of nursing student and faculty interactions with mothers of pre-school children enrolled in a Headstart program. During these experiences, observations related to the needs of the mothers included poor health practices (smoking, being overweight), lack of motivation, statements of feeling depressed, difficulty making decisions, feelings of being overwhelmed by parenting demands, powerlessness, and disenfranchisement. This descriptive, correlational study was designed to determine the value of health, incidence of depression, and characteristics of self-esteem among low-income mothers of pre-school children. This sample of convenience was comprised of 133 low-income mothers who responded to a mailed survey. Three instruments were used in the study: the Wallston and Wallston Health Values Scale, the Center for Epidemiologic Studies Depression Scale (CES-D), and the Rosenberg Self-Esteem Scale. Data were analyzed by collection of frequency of response, which was then converted to a percentage. To determine if differences existed in respect to demographic variables, ANOVA (self-esteem and depression) and Chi Square (health) measures were used. Participation in activities outside the home accounted for a significant difference in self-esteem. Mothers involved in activities reported higher self-esteem. The findings suggest that participation in activities may increase self-esteem and lower depression. Over three-quarters (85%) of mothers placed a high value on health. Based on their high valuing of health and the potential for increasing self-esteem through activity, it can be concluded that the women in this sample will benefit from planned health activities. It is also anticipated that, because of the strong relationship between self-esteem and depression, women who participate in these activities will demonstrate lower levels of depression. PMID- 2272854 TI - Preparing sexually abused girls for genital evaluation. AB - Sexually abused children need physical evaluation to determine if they have been injured, infected, or impregnated by the activity, and to reassure them about their bodies. The physical evaluation can be very frightening because it may involve sensations similar to those felt during the abuse. In order to cope, children need information about the purpose and process of the procedure, the sensations and emotions they can expect to experience, and training in how to manage their emotional responses. This protocol is offered as a structure for providing the information in a timely and effective way. PMID- 2272855 TI - Coping strategies of chronically ill adolescents and their parents. AB - The purpose of this exploratory pilot study was to determine the coping strategies used by adolescents with chronic illnesses and compare those strategies with the strategies used by their parents. Adolescent coping strategies were measured by the Jaloweic Coping Scale, while parental perceptions of their coping strategies were assessed using the Hymovich Chronicity Impact and Coping Instruments: Parent Questionnaire (CICI:PQ). Fifteen chronically ill adolescents and their parents were administered the tools. Analysis revealed that there were significant differences between the parent coping strategies and those of the adolescents in the sample. Adolescent responses on the three subscales of the Jaloweic Coping Scale were analyzed with ANOVA, resulting in no significant differences in responses on the three subscales. PMID- 2272856 TI - A comparison of mothers' and fathers' perceptions of caring for an infant requiring home cardio-respiratory monitoring. AB - The purpose of this study was to compare (a) what fathers and mothers considered stressful about caring for a cardio-respiratory monitored infant at home and (b) how they coped with this experience. Twenty-three father and mother pairs with infants currently receiving or having received home cardio-respiratory monitoring within the past six months were interviewed in their homes. Content analysis of interview data revealed five types of stressors and ten coping strategies used to manage these stressors. Fathers and mothers described similar stressors and coping strategies. Differences existed in how fathers and mothers interpreted these stressors and the type of strategies used. PMID- 2272857 TI - Anxiety and depression in mothers of low birthweight and very low birthweight infants: birth through 5 months. AB - The purpose of this study was to compare two common psychologic stress responses, anxiety and depression, in 27 mothers of very low birthweight (VLBW; less than or equal to 1500 grams) preterm infants and 35 mothers of low birthweight (LBW; 1501 2500 grams) preterm infants from the time of the infant's birth until the infants reached 5 months adjusted gestational age. There were significant differences in the patterns of anxiety and depression experienced by mothers of LBW and VLBW infants over time. Mothers of VLBW infants had higher anxiety and depression until 2 months adjusted gestational age while mothers of LBW infants had higher anxiety and depression at 3 and 4 months. Nursing interventions designed to decrease stress during the first postpartal week and to counsel mothers about patterns of anxiety and depression they may experience over time may be useful. PMID- 2272858 TI - Goal or near miss! Movement potential differences between adults and children in skilled performance. AB - In this study, the performances and the movement-related brain macropotentials of a group of adults and 10-year-old children were analyzed to test whether and how they were correlated to the success or failure in the performance. Bereitschaftspotential (BP), motor cortex potential (MCP) and skilled performance positivity (SPP) related to preparation, execution and evaluation of performance respectively showed a significant relationship to the performance outcome. The BP area in the left precentral decreased significantly with increasing performance time. The amplitude of the MCP was maximum during target performances and decreased with increasing range of error of performance. There was a difference in trend between adults and children in the SPP latency. During target performances, SPP latency in Pz was maximum in children and minimum in adults. In children, the SPP amplitude was greater in frontal and precentral areas during target performance and decreased with increasing inaccuracy of performance. This trend was not evident in adults. The results seem to indicate that the SPP latency does not seem to depend on the performance time but on the evaluation of information conveyed by the stimulus. How this evaluation takes place seems to be different in children and adults; this evaluation process is also reflected in the SPP amplitude of children during target performances. For the adults who have already developed formal thinking, the probability that any outcome is possible exists and so the significant relationship between SPP amplitude and performance is not seen. PMID- 2272859 TI - Covariation and reliability of ECG parameters during 24-hour monitoring. AB - Although diverse ECG parameters are used in psychophysiology, relatively little is known of the covariation and reliability of these parameters. In the present study with 31 male cardiac patients, 24-h ambulatory ECG monitoring was used to describe the covariation and reliability of 18 ECG parameters. Analysis of the ECG parameters was done beat-by-beat and averaged on a 5-min basis. To describe different aspects of covariation, partitioning of covariance was used, yielding within-subjects, within-time periods, and residual correlations. Moreover, reliability was assessed for different time lags between 5 min and 22 h. Results indicate that the ECG parameters are only partly redundant, since several correlation clusters emerged with low correlations between these clusters. In order to utilize more information from the ECG, at least heart rate, heart rate variability, ST-amplitude, QRS-duration, and one of the main ECG waves (P-, R-, T wave) would be necessary. Reliability was high for all parameters except heart rate variability measures. PMID- 2272860 TI - EEG correlates of hypnotic susceptibility and hypnotic trance: spectral analysis and coherence. AB - EEG was recorded monopolarly at frontal (F3, F4), central (C3, C4) and occipital (O1, O2) derivations during A-B-A conditions of waking rest, hypnosis (rest, arm immobilization, mosquito hallucination, hypnotic dream), and waking rest. Stringently screened on several measures of hypnotic susceptibility, 12 very low hypnotizable and 12 very highly hypnotizable, right-handed undergraduate, subjects participated in one session. Evaluations were Fast-Fourier spectral analysis, EEG coherence between selected derivations and maximum spectral power within EEG bands. In eyes open and closed conditions in waking and hypnosis, highly hypnotizable subjects generated substantially more mean theta power than did low hypnotizable subjects at all occipital, central and frontal locations in almost all conditions of waking and hypnosis, with a larger difference in frontal locations. Both low and high hypnotizables showed increased mean theta power in hypnosis, suggesting an intensification of attentional processes and imagery enhancement. Mean alpha power was never a predictor of hypnotic susceptibility. Interactions with hypnotic susceptibility showed that highly susceptible subjects had more beta activity in the left than right hemispheres, while low susceptible subjects showed only weak asymmetry. No main effects for or interactions between waking/hypnosis and hypnotic level were found for coherence between derivations or maximum spectral power within theta, alpha and beta EEG bands. PMID- 2272861 TI - Neurophysiological correlates of verbal activity in patients with speech disorders of traumatic etiology. AB - The article deals with the neurophysiological correlates of the pathophysiological mechanisms of brain trauma. Mechanisms of damaged function restoration by means of therapeutic electrostimulations (TES) are also under discussion. Localization of the brain zones involved in the maintenance of speech and their expansion, while TES is shown on the basis of functional testing and registration of different indices of bioelectrical activity. PMID- 2272862 TI - Neurophysiological and neuropsychological study of two cases of multiple personality syndrome and comparison with chronic hysteria. AB - Two cases of multiple personality were studied neurophysiologically and neuropsychologically. Bilateral frontal (Right greater than Left) and left temporal dysfunction was present in both cases, on neuropsychological indicators. Both cases on EEG analysis, were in a state of relative left hemisphere activation, across all cerebral regions and task conditions. The one case who was cured with hypnotherapy, after recovery showed normal left hemisphere functions neuropsychologically but remained in a state of relative left hemisphere activation electrophysiologically. This is in contrast to women with chronic hysteria who exhibit relative right hemisphere activation in all regions and across all conditions. Both patients were unmedicated throughout. A neurophysiological model to account for these findings is presented. PMID- 2272863 TI - Probability and inter-stimulus interval effects on the P300 from auditory stimuli. AB - The relationship between target stimulus probability and inter-stimulus interval (ISI) on the P300 (P3) component of the event-related potential was assessed in two experiments. An auditory discrimination paradigm was employed wherein subjects indicated with a finger tap response the occurrence of a randomly presented 2000 Hz target tone embedded in a series of 1000 Hz tones. Experiment 1 presented stimuli with target probabilities of 0.10, 0.30, and 0.50 at ISIs of 1.5 or 3.0 s and produced P3 amplitudes which decreased with increases in target probability and were smaller at the shorter compared to the longer ISI. Experiment 2 presented stimuli with target probabilities of either 0.20, 0.50, or 0.80 at ISIs of 4.0 and 10.0 s and produced P3 amplitudes which were unaffected by either variable. P3 latency demonstrated relatively few changes in either experiment. When taken together with previous findings, the results suggest that inter-stimulus interval affects P3 amplitude by determining the amount of processing resources available during ERP generation. PMID- 2272864 TI - The influence of user status and anxious disposition on the hypertensive effects of caffeine. AB - The present study examined the influence of consumer status and anxious disposition on the hypertensive effects of caffeine. A secondary aim of the study was to investigate possible gender differences in response to caffeine. Sixty normotensive subjects were assigned to 4 groups representing high and low scorers on the variables of habitual caffeine consumption and anxious disposition. A randomized double-blind crossover design was used in which all subjects received a placebo (lactose) at one of two 120-min laboratory sessions and caffeine (6 mg/kg) at the other. Systolic and diastolic blood pressure, heart rate, hand steadiness, and EMG were monitored before and after exposure to a psychological stressor. Caffeine produced significant elevations in systolic and diastolic blood pressure, and these effects were additive to the pressor effects of stress and anxiety. While the general pattern of results was similar for both sexes, reactions to caffeine were more pronounced in males than in females. Notwithstanding the need for clarification of the chronic effects of caffeine, present findings add further weight to current concerns about the acute hypertensive effects of the drug. PMID- 2272865 TI - Ambulatory monitoring in sleep apnoea presenting with nocturnal episodic phenomena. AB - Episodic nocturnal phenomena represent a separate cluster of disturbances within the classification of sleep disorders. The reported case history covers paroxysmal signs occurring secondary to a REM-dependent mixed sleep apnoea syndrome. The pathophysiology of similar episodes in elderly (non)epileptic patients is discussed. Ambulatory monitoring is an appropriate technique for investigation if respiratory and motor activity, and EEG and ECG are recorded simultaneously. PMID- 2272866 TI - Cardiac deceleration and E-wave brain potential components in young, middle-aged and elderly adults. AB - Event-related potentials (ERPs), heart rate, and behavioral data were recorded from young, middle-aged, and elderly adults during an S1-S2 recognition memory paradigm. Anticipatory and evoked cardiac decelerations decreased significantly with age, as did the accuracy of recognition memory. The E-wave prior to S2 did not differ with age, however, and was not correlated with heart rate deceleration in any age group. Correlations between physiological measures and performance were weak in all groups. Taken together, the data provide little support for the hypothesis that the poorer recognition memory of older adults is related to an increasing uncoupling of E-wave and anticipatory heart rate with age. PMID- 2272867 TI - A developmental study of event-related potentials during explicit and implicit memory. AB - Event-related potentials (ERPs) were recorded from children, adolescents and adults in response to drawings of common objects or their printed names. Explicit memory was assessed in a continuous recognition paradigm, where each item had (old) or had not (new) been presented earlier. Implicit memory was assessed in separate blocks of pictures and words where item repetition was incidental to the assigned task of identifying stimuli in a given semantic category. Accuracy measures replicated the finding that word memory decays more rapidly than picture memory. A larger anterior negativity to pictures than words in children, but not adolescents or adults, suggested the existence of separate picture/word processing mechanisms that undergo developmental change. ERP repetition effects involved at least two components: a negativity that was larger to new items in both tasks, and a subsequent centroparietal positivity, most likely P3b, that was larger in response to old items for the explicit task only. Both components did not appear to undergo developmental change. PMID- 2272868 TI - Visuomotor tracking performance and task-induced modulation of alpha activity. AB - This study is an attempt at clarifying the relationships between defined environmental demands, the efficiency of corresponding visuomotor behaviour and the EEG. We made use of a laboratory paradigm which was devised to closely represent a common man-machine system process, i.e, maintaining of a road vehicle on a predetermined track when squally wind is blowing from the flank. The deviation of the ideal track represents the input signal for the component system man, the compensating steering motion its output signal. This performance is modelled by a visuomotor tracking task which has been developed as a means of ascertaining subtle effects of psychotropic drugs and described elsewhere. We found that the higher the efficiency of test performance, the lower was the task induced modulation of alpha-activity. PMID- 2272869 TI - Questions attribution of porcine enteritis to Campylobacter spp. PMID- 2272870 TI - Confronting equine colic through new approaches. PMID- 2272871 TI - USDA expands early warning system for harmful food bacteria. PMID- 2272872 TI - Veterinary technicians are great investment. PMID- 2272874 TI - Liability protection for laboratory animal and public veterinarians. PMID- 2272873 TI - Vicksburg veterinarian. PMID- 2272875 TI - Statistics simplified. Comparing proportions. PMID- 2272876 TI - ECG of the month. PMID- 2272877 TI - Efficacy of tiamulin against experimentally induced Streptococcus suis type-2 infection in swine. AB - Eighteen 4-week-old pigs were used in a study to evaluate tiamulin in drinking water for control of experimentally induced Streptococcus suis type-2 infection. Pigs in groups A and B (n = 6 pigs/group) were aerosolized with a logarithmic growth phase culture of S suis type 2, whereas pigs in group C (n = 6 pigs) served as noninfected and nonmedicated controls. After exposure to S suis, pigs in group B were given 180 mg of tiamulin/L of drinking water for 5 days. Pigs in group B consumed more feed (P = 0.009) and gained body weight faster (P = 0.02) than did pigs in group A. Pigs in group A had higher rectal temperature (P = 0.05) for up to 7 days after S suis exposure, higher clinical sign scores (P = 0.008), higher serum cortisol concentration on days 7 and 14, higher gross lesion scores (P = 0.03), and higher microscopic lesion scores (P = 0.01) than did pigs in groups B and C. Gross and microscopic lesions in pigs of groups A and B included meningitis, pneumonia, pleuritis, pericarditis, peritonitis, and synovitis of variable severity. Streptococcus suis type 2 was recovered from tissue specimens of 2 group-A pigs and 1 group-B pig. Data indicated that tiamulin administered via drinking water significantly reduced the effects of S suis type-2 infection. PMID- 2272878 TI - Serum ionized calcium concentration in clinically normal dairy cattle, and changes associated with calcium abnormalities. AB - Serum ionized calcium (ICa) concentration was determined in 141 clinically normal dairy cattle by use of a direct-measuring calcium ion-selective electrode instrument. Mean serum ICa concentration 2 hours after blood withdrawal was 4.59 mg/dl; range varied from 3.79 to 5.25 mg/dl. Regression analysis indicated a high degree of correlation between ICa and serum total calcium concentrations if serum stored at 23 C was analyzed within 12 hours after blood withdrawal. Abnormal ICa concentration was detected in 19 of 85 dairy cows that were affected with various pathologic conditions. All 19 cows had hypocalcemia (n = 13 with parturient hypocalcemia, 4 with hypomagnesemic tetany, and 2 with renal disease). In all cases, the ICa concentration clearly related to the clinical manifestation of disease and the functional status of the cow's calcium metabolism. PMID- 2272879 TI - Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy. AB - Baseline plasma norepinephrine (NE) and epinephrine (EPI) concentrations were measured in dogs with naturally acquired heart failure (HF) caused by either degenerative mitral valve disease and mitral regurgitation (MR) or idiopathic dilated cardiomyopathy (DCM). Compared with controls (clinically normal), dogs with HF had increased plasma NE concentration, which was correlated positively with clinical severity of HF. Dogs with the most severe degree of HF (New York Heart Association functional class IV) had mean NE concentration significantly (P less than 0.05) greater than that of dogs with all other functional classes of HF. Overall, mean NE concentration in dogs with DCM was greater than that in dogs with MR. Plasma EPI concentration was not different between control dogs and dogs with HF or between dogs with DCM or MR. Correlations were not found between the echocardiographically derived end systolic volume index (used as an estimate of myocardial function) and plasma NE and EPI concentrations or serum sodium or potassium concentration. Dogs with DCM, as a group, had a small but significant (P less than 0.05) decrease in serum sodium concentration, compared with dogs with MR. This difference was maintained only for class-IV HF when dogs were separated according to functional HF class. In dogs with DCM, significant inverse correlation was found between plasma NE and serum sodium concentrations. When grouped together, all dogs with HF maintained this relationship; however, dogs with MR did not have correlation between plasma NE and serum sodium concentrations. Plasma EPI and serum sodium concentrations were not correlated for any group. It was concluded that in dogs, plasma NE, but not EPI, concentration is high in relation to the clinical severity of naturally acquired HF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272880 TI - Coliform myositis in a calf. AB - Coliform myositis was diagnosed in a young calf with signs of pain, swelling, and edema of the right hind limb. Diagnostic methods included bacteriologic culture and antimicrobial susceptibility testing. The organism isolated was a gas producing Escherichia coli. The infection responded to administration of trimethoprim/sulfadiazine, to which the organism was susceptible in vitro. PMID- 2272881 TI - Systemic lupus erythematosus in a filly. AB - Systemic lupus erythematosus (SLE) was diagnosed in a 2-year-old Standardbred filly. Clinical signs of SLE included weight loss, bilateral symmetric alopecia, seborrhea, oral ulceration, and lymphadenopathy. Abnormal laboratory findings included a Coombs test-positive hemolytic anemia and positive antinuclear antibody test result. Histologic evaluation of multiple skin biopsy specimens revealed interface dermatitis with linear deposition of IgG at the basement membrane zones of the epidermis and hair follicles. The filly did not respond to glucocorticoid treatment and was euthanatized. Necropsy findings included membranous glomerulonephritis and fibrous synovitis. On the basis of these findings, SLE should be considered in the differential diagnosis of immune mediated skin disease in horses. Definitive diagnosis of SLE relies on recognition of multisystemic disease and confirmatory histopathologic and immunopathologic findings. PMID- 2272882 TI - Prostatic adenocarcinoma in a cat. AB - Prostatic adenocarcinoma was diagnosed in an 11-year-old neutered cat. Clinical signs of the disease included hematuria and a mass in the caudal portion of the abdomen. Prostatectomy was performed. Doxorubicin was administered IV at a dosage of 30 mg/m2 of body surface, followed by cyclophosphamide (300 mg/m2, IV). After 4 treatments, low urine specific gravity and proteinuria developed, and treatment was discontinued. The cat was euthanatized 10 months after surgery because of recurrence of the neoplasm. Necropsy revealed metastasis to the lungs and pancreas. PMID- 2272883 TI - Vitamin K-dependent multifactor coagulopathy in Devon Rex cats. AB - A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder. PMID- 2272884 TI - Metastatic thyroid solid-follicular carcinoma in the cervical portion of the spine of a dog. AB - A metastatic thyroid solid-follicular carcinoma in the cervical portion of the spine was responsible for severe tetraparesis in a dog. Myelography revealed an extradural compressive lesion dorsal and to the right of the midline of C3. Histologic examination was used to diagnose the mass as a solid-follicular thyroid carcinoma. The primary tumor was not evident on cervical palpation or radiography. A dorsal laminectomy centered over C3 was performed, and all visible tumor was removed from the spine. The owner declined any further treatment for the dog. PMID- 2272885 TI - Primary left ventricular hemangiosarcoma diagnosed by endomyocardial biopsy in a dog. AB - An 8-year-old spayed Golden Retriever was examined because of recent onset of congestive heart failure complicated by ventricular arrhythmias. Echocardiography revealed a thickened, hypokinetic region of the left ventricular free wall. Fluoroscopically guided transarterial endomyocardial biopsy of the hypokinetic region of the left ventricle revealed infiltration of the endocradium by neoplastic cells consistent with hemangiosarcoma. The dog's clinical condition deteriorated 7 weeks later, and necropsy confirmed the diagnosis and primary site of origin of the tumor. This report describes the clinical use of an endomyocardial biopsy technique to diagnose an infiltrating myocardial tumor that was associated with signs mimicking canine dilated cardiomyopathy. PMID- 2272886 TI - Epizootiologic patterns of diabetes mellitus in cats: 333 cases (1980-1986). AB - Medical records from 333 cats with diabetes mellitus were studied retrospectively, using epidemiologic methods to determine the incidence of and risk factors for diabetes mellitus in this species. Abstracts were derived, using the Veterinary Medical Data Program with its 17 participating academic institutions in the United States and Canada. A reference population of 135,651 cats was derived from the same hospital population and time span (July 1980 to June 1986). The incidence of diabetes mellitus in cats was determined to be 2.45 cases/1,000 cat-years-of-risk during the 6-year study period. Breed had no detectable effect on risk for diabetes mellitus. In contrast, body weight, age, gender, and neutering had a significant (P less than or equal to 0.01) effect. Body weight of cats was categorized as being less than or greater than or equal to 6.8 kg. The higher body weight, probably indicating obesity, contributed a 2.2 fold increase in risk, even after adjustment for age and gender (adjusted odds ratio). The etiologic fraction for high body weight was 3.8%, suggesting that an estimated 3.8% of cases of diabetes mellitus was attributable to this factor alone. Over 50% of diabetic cats were greater than 10 years old, and the etiologic fraction for age greater than 7 years alone was 73.5%. Age was a significant (P less than 0.001) and the most important single risk factor for development of the disease in cats, with adjusted odds ratios of 8.3 and 14.4 for age 7 to 10 years and greater than 10 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272887 TI - Treatment of slipped capital femoral epiphysis in cattle: 11 cases (1974-1988). AB - A mixed population of 11 cattle (7 dairy, 4 beef; 9 male, 2 female) were examined because of acute onset of non-weightbearing hind limb lameness. Radiography revealed slipped capital femoral epiphyseal fracture in all cattle, with the exception of one large bull. Ten of the 11 cattle were treated with open reduction and internal fixation, using intramedullary pins. Cattle affected with slipped capital femoral epiphyseal fracture in previous reports typically have been calves that required forced extraction during dystocia. Cattle in this report were in the following 2 age groups in which trauma was the likely cause: 3 to 5 months and 1.5 to 2.3 years. Follow-up information was provided for 7 of the 10 cattle. Four of the 7 were functional and had no clinical signs of arthritis, abnormal gait, atrophy, scarring, contralateral compensation, breakdown, or other difficulty 6 months after surgical correction. If early diagnosis is achieved, it appears that reduction with intramedullary pinning can provide a good long-term prognosis in cattle when function as breeding animals is important to their future value. PMID- 2272888 TI - What is your diagnosis? Heterogeneous abdominal mass in the right cranioventral portion of the abdomen. PMID- 2272889 TI - The collaborative roles of universities and hospitals in addressing the allied health manpower shortage. PMID- 2272891 TI - An investigation of academic dishonesty in allied health: incidence and definitions. AB - Educators in the health sciences are concerned about academic dishonesty and are searching for methods to control misconduct. If students falsify academic work, their behavior pattern may continue in professional practice, endangering the health and well-being of the patients in their care. This paper presents the results of a study of the attitudes and experiences regarding dishonest academic behaviors of a sample of 244 students and 31 faculty in the School of Health Professions at Southwest Texas State University. Student and faculty definitions of dishonest behavior were compared, and the incidence of dishonest behavior and the experiences of faculty in recognizing and disciplining students for academic misconduct were analyzed. Major findings included: 1) faculty, undergraduate, and graduate students differ in their definitions of some types of dishonest behavior; and 2) the most common types of dishonest behavior identified by faculty and students involve cheating and plagiarism. Future research is warranted with attention given to the causal factors leading to academic dishonesty and patterns of dishonesty in academic and practice settings. PMID- 2272890 TI - Healthy People 2000: national health promotion and disease prevention objectives (excerpts). US Public Health Service. AB - The US Public Health Service recently completed and published Healthy People 2000: National Health Promotion and Disease Prevention Objectives. The report is the culmination of a national effort, representing the work of citizens, professionals, organizations, and communities, and the cooperation of numerous federal agencies. The overall goal of the report and its objectives are to prevent unnecessary disease and disability and to achieve a better quality of life for all Americans. PMID- 2272892 TI - Occupational attainment in selected allied health professions. AB - This study examined the factors in the process of occupational attainment for a single group, the allied health professions. A 14-variable causal model was developed to explain postcollege attainment of a job in one of five allied health professions: medical dietetics, medical social work, occupational therapy, physical therapy, or speech therapy. The sample was composed of 272 college students who responded to the Cooperative Institutional Research Program surveys of 1971 and 1980. Analysis indicated that several variables, including academic integration, having a science major, and being oriented to service, had significant direct effects on attainment in the allied health professions. Knowledge of the personal characteristics and achievements of those who successfully enter jobs in the allied health professions may allow informed student and faculty choices and reduce recruitment and retention problems in schools of allied health. PMID- 2272893 TI - Assessment of need for multicompetent allied health practitioners in the midlands of South Carolina. AB - Recent attention has focused on integration of Multicompetent Allied Health Practitioners (MCAHPs) into the health care labor force to offset future imbalances in supply and demand for allied health practitioners, and to maximize use of existing allied health practitioners. Several recent studies have focused on multicompetency issues. However, there is little that shows the impact of MCAHPs on health care costs. This study was conducted to determine the current usage of MCAHPs, projected future need for them, needs-skill combinations, entry level salary comparison between MCAHPs and single-skilled practitioners, projected yearly savings in personnel costs to health care organizations employing MCAHPs, and community support for a college-based MCAHP program. Results indicated a large market for MCAHPs, increased entry-level salaries for MCAHPs compared to single-skilled practitioners, and projected savings to health care institutions due to decreased personnel costs. PMID- 2272894 TI - Impacting moral reasoning in allied health students. AB - This study was designed to assess the relative impact of a course in biomedical ethics on the moral reasoning skills of junior-level students in a school of allied health. A pretest-posttest nonequivalent control group design was used. The course was found to significantly impact principled moral reasoning scores as measured by Rest's Defining Issues Test (DIT). Male-female differences in DIT score changes were also suggested. The nature of the instruction appears paramount to possible changes in moral thinking, indicating that moral education programs need to emphasize dilemma discussion in their formats. PMID- 2272895 TI - Characterisation of afferent projections to the nucleus ambiguus of the rat by means of fluorescent double labelling. AB - The rat nucleus ambiguus (Amb nucleus) is composed mainly of laryngeal and pharyngeal motoneurons, and can be differentiated into three main subdivisions with respect to the morphology, distribution and physiological function of their neurons. The medial parabrachial and Kolliker-Fuse nuclei (MPB/KF), and the lateral nucleus of the solitary tract (SolL) play a modulator role over some of the physiological functions assigned to the Amb nucleus. The location and characteristics of labelled neurons in the MPB/KF, SolL and Amb nuclei have been studied following the simultaneous and bilateral injections of True blue and Diamidino yellow in each of the three subdivisions of the Amb nucleus. All of the identified axonal projections were mainly ipsilateral. Some of the described pathways also have collaterals which connect both sides of the Amb complex. PMID- 2272896 TI - Involution of human fetal Leydig cells. An immunohistochemical, ultrastructural and quantitative study. AB - The testes of stillborn fetuses (from 13 to 28 weeks of gestational age), fetuses born alive (from 29 weeks of gestational age) who died a few days later, and infants dying 1 to 8 months after birth were processed for light and electron microscopy. Paraffin-embedded material was stained with the avidin-biotin peroxidase complex (ABC) method for immunohistochemical detection of testosterone (T) in order to quantify the age-related changes in the number of T-positive interstitial cells. This number decreased progressively from the 24th week of gestation up to birth and remained unchanged up to the second month of postnatal life. During the third month of age, the number of T-positive cells rose markedly but fell again from the fourth month to the end of the study. The ultrastructural study revealed the following types of interstitial cells at all ages studied: fibroblast-like cells, myofibroblast-like cells, developed fetal Leydig cells, degenerating fetal Leydig cells and infantile Leydig cells with a multilobed nucleus and focal cytoplasmic accumulations of smooth endoplasmic reticulum and lipid droplets. Quantitative ultrastructural studies revealed that the changes in the number of fetal Leydig cells with age were similar to those found in the number of T-positive cells although, for each age studied, absolute values were higher in the ultrastructural study. The number of infantile Leydig cells increased with age. PMID- 2272897 TI - Morphometric studies on the development and sexual dimorphism of the submandibular gland of the mouse. AB - A light microscopic morphometric analysis of the development of the mouse submandibular gland has been carried out from birth up to the age of 6 weeks. At birth the bulk of the gland consists of approximately equal volume proportions of acinar, terminal tubule and non-secretory cells. The granular convoluted tubule is absent at birth. The neonatal female gland resembles that of the male in many respects. With the regression of the terminal tubule at 2 weeks of age the duct system of the gland is seen to differentiate into excretory, striated and intercalated ducts. The volume proportions of the gland constituents of the female are similar to those of the male at 2 weeks. At this age, the acini occupy 55%, the striated duct 20% and the intercalated duct 15% of the total gland volume. Sexual dimorphism is clearly evident in the gland at 4 weeks of age when the duct system is seen to differentiate to form its granular convoluted tubule component. The granular tubule occupied 19% of the gland volume in the male but only 8% in the female at 4 weeks. The proportions of acini are only 41% in the total gland volume of the male mouse but 62% in the female at 4 weeks. In the male gland the proportions of granular convoluted tubule increase from 13% to 21% between 4 and 6 weeks and the secretory granule content of these cells from 6% to 24%. At 6 weeks of age the volume proportion of granular convoluted tubule in the male is 45% and that in the female is only 12%. At this age the acini occupy a proportion of 30% in the male gland as opposed to 57% in the female gland. At 6 weeks the volume of granular convoluted tubule cells is 40% lower in the female (1842 microns 3) than in the male gland (2995 microns 3). PMID- 2272898 TI - A morphological and morphometric study of the prosimian lung: the lesser bushbaby Galago senegalensis. AB - The lung of the lesser bushbaby (Galago senegalensis) has been investigated morphologically and morphometrically using the transmission and scanning electron microscopes. Grossly and microscopically, the bushbaby lung was found to be essentially similar to that of the other primates and the mammals in general. Subtle morphometric differences were, however, observed, with the bushbaby lung being generally structurally less sophisticated than that of the other primates on which comparable data are available, except for man. The weight-specific surface area of the blood-gas (tissue) barrier in G. senegalensis was 25 cm2 g-1. The thickness of the blood-gas barrier was 0.355 micron and the weight specific total anatomical pulmonary diffusing capacity 0.045 mlO2 sec-1 mbar1 kg-1. The morphological similarity of the galago lung to that of man gives sufficient grounds to justify its possible use in human pulmonary studies but caution has been called for in the general utilisation of primate tissues without first establishing their morphological characteristics, just because the primates are taken to be evolutionally close to man. The dearth of morphological studies on the various organ systems of the prosimians is pointed out. PMID- 2272899 TI - Neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON) in the developing and adult spinal cord of a reptile. AB - The developmental pattern and the adult distribution of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON) were investigated in the spinal cord of the lizard Gallotia galloti. Embryonic, postnatal and adult animals were studied by means of the immunohistochemical technique. Neurons containing both peptide immunoreactivities first appeared at the embryonic Stages 37/38. Immunoreactive perikarya were more numerous in the embryonic than in either the postnatal or the adult spinal cord. Fibres immunoreactive for both antisera appeared around the time of hatching, being numerous and widespread in the adult spinal cord. NPY- and C-PON-like-containing neurons and fibres in the adult spinal cord of Gallotia galloti were related to sensory, autonomic and motor areas. PMID- 2272900 TI - Subfibrillar architecture and functional properties of collagen: a comparative study in rat tendons. AB - Collagen fibrils from different rat tendons have been investigated by freeze fracture and transmission electron microscopy. In all cases, marked differences in both fibril morphology and subfibrillar organisation have been consistently found between the tendon core (composed of large and heterogeneous fibrils comprising tightly-packed, straight, parallel molecules) and sheath (showing small, uniform collagen fibrils with a helical arrangement of the molecules). The bio-mechanical requirements to which these tissues are subjected suggest, as do previous observations on other tissues, that a causal correlation exists between substructure and collagen fibril function. PMID- 2272901 TI - An in vivo assessment of muscular activity and the importance of electrical phenomena in bone remodelling. AB - Modified orthopaedic pins were placed close to the medial and distal epiphyses of the tibia in 4 anaesthetised rabbits, in order to allow the application of controlled external loading cycles. Rosette strain gauges were placed at midshaft level, where the greatest compressive and tensile strains were expected during loading. Two weeks later, following stabilisation of the pins by bone healing, the animals were anaesthetised again and silver-silver chloride electrodes were attached close to the strain gauges in order to measure the changes in electrical potential difference. A sinusoidal load cycle was exerted between the pins with peak levels of 100 N or 250 N depending on the age of the animal. A fluctuation in potential difference, in synchrony with the strain recorded by the strain gauges, was recorded. The maximum potential difference was 2.2 mV, and it was not possible to exceed this with increased bone strain. After demonstration of the piezoelectric effect, repeated stimuli were applied to the sciatic nerve, producing a twitch in the muscles adjacent to the tibia. The electric potential difference from the muscles completely overwhelmed the local potential difference at the bone surface. A further two animals were prepared as previously described, and one electrode was placed on the endosteal surface. The electrical events mirror the changes found across the limb. The stimulus to bone remodeling, as distinct from growth, is usually loading in association with muscular activity. The fact that the changes in electrical fields at the bone surface are predominantly those originating in the muscles indicates that local electrical phenomena generated by bone strain cannot be the factors initiating the cellular response that is responsible for bone remodeling. PMID- 2272902 TI - Comparative morphometry of the mammalian brain: estimates of cerebral volumes and cortical surface areas obtained from macroscopic slices. AB - Stereological methods for obtaining unbiased estimates of brain volumes and surface areas are illustrated on fixed brains (cerebrum only) from mammals varying in body weight between 2 kg (cat) and 550 kg (ox). Brain sampling was designed so that Cavalieri estimates of volumes (derived via point counting) could be combined with vertical sectioning estimates of surface areas (via intersection counting). Total volumes, cortical volumes and cortical surface areas were calculated. Each cerebral hemisphere was cut into 3 slabs. Each slab was cut further into macroscopic, parallel vertical slices having a uniform random start position. The term vertical as used here signifies orthogonal to the medial aspect of the hemisphere. The direction of vertical slices also had a random start but was varied systematically across the slabs. Test lattices bearing test points and cycloid test lines were superimposed on vertical slices. Fixed volumes and surfaces were corrected for shrinkage effects. A worked example of the calculation sequence is provided. The experimental design was flexible. Brains of different sizes could be analysed by simply altering the distance between slices and the size of the test lattice. Analyses took 30-45 minutes per hemisphere. Whilst volumes and surfaces increased with body weight, specific values declined. Thus, specific surfaces for the cortex fell from 25 cm2/kg (cat) to 2 cm2/kg or less (pig and ox). PMID- 2272903 TI - The effect of diet on bone shape in the mouse. AB - The effects of four deficient diets (oats, barley, wheat, buckwheat) on the shape of first and second cervical vertebrae and scapulae in C57BL mice have been measured using Fourier analysis. Bone shape was found to be robust, and only minimally affected by dietary change. The significance of this lack of change is discussed in the light of changes induced by diet in non-metrical variants in the skeleton. The study further emphasises the dangers of using certain non-metrical characters in taxonomic studies and indicates that the shapes of mouse bones are affected to a lesser degree by dietary influences than are the incidences of certain non-metrical character states. PMID- 2272904 TI - Sexing of human hip bones. AB - Eight measurements of the hipbone were taken from 62 human skeletons of unknown sex. The subjective judgements of eight experienced anatomists were used to obtain subsets of male, female and unknown sex specimens. Principal components analysis was employed as a group-finding procedure; this confirmed the subjective determinations. Discriminant function analysis, using the subjectively determined 'known' specimens, was conducted. This yielded scores which sexed the unknown subset in agreement with the groups found by principal component analysis. Further discriminant functions were calculated to exclude two hip bone measures which were shown to be poor indicators of sex. The specimens with discriminant function scores closest to the cut-off point were seen, in the graph of the first two principal components, to lie in a cluster intermediate between the main gender groups and, upon re-examination, these were found to be rather ambiguous specimens with small overall measures and a narrow sciatic notch and pubis. The results of this study indicate that mid-pubic width is a more useful sexing character than pubic length. PMID- 2272905 TI - Kinetic parameters in the growth plate of normal and achondroplastic (cn/cn) mice. AB - We have reinvestigated the overall size, zone size, mitotic rate and growth rate in the tibial epiphysis of normal and achondroplastic (cn/cn) mice aged 7-55 days. Our present sample did not contain the two phenotypes characteristic of some stocks carrying the gene: cn/cn mice showed smaller zone sizes within the growth plates, smaller cells, decreased mitotic indices and growth rates. PMID- 2272906 TI - The monoptychic glands of the jugulo-sternal scent gland field of Tupaia: a TEM and SEM study. AB - The monoptychic 'apocrine' scent glands of the sternal region of two adult male Tupaia belangeri were studied by transmission and scanning electron microscopy, in order to assess the modes of release of their secretory products. In segments of the secretory tubules with a narrow lumen the epithelial cells are columnar and are firmly connected to each other by desmosomes and junctional complexes. Myoepithelial cells are interspersed between the secretory epithelium and the basement membrane. The cytoplasm of the secretory epithelial cells contains granular and agranular endoplasmic reticulum, mitochondria, Golgi apparatus, lysosomes and secretory granules. The free surface of the secretory epithelium is furnished with densely arranged microvilli. The apices of the cells protrude as dome-shaped extensions into the glandular lumen. At the tip of these extensions cellular processes of irregular shape are found. The surface of these processes shows no microvilli. They contain densely packed and dilated cisternae of agranular endoplasmic reticulum and free ribosomes. The constriction of the base of these processes and the occasional observation of a 'demarcation membrane' between a process and the secretory cell indicate that these secretory processes become detached from the secretory cells according to the apocrine mode of extrusion. Within the glandular lumen they break down and form secretion. Parallel to this apocrine extrusion the same cells produce secretory granules, the diameter of which measures 300-900 nm. The contents of these granules are released into the glandular lumen by exocytosis according to the eccrine mode of secretion. This resembles the situation in other mammals in which monoptychic glands release their secretory products by means of both apocrine and eccrine extrusion. Therefore monoptychic skin glands should not be classified into apocrine and eccrine glands. Our results corroborate Schaffer's (1927, 1940) more general classification of exocrine glands according to the nature of the secretory epithelium into monoptychic and polyptychic glands. PMID- 2272908 TI - A morphological study of the tracheal epithelium of the snake Natrix maura. AB - The epithelium of the trachea of the Natrix maura snake was studied by conventional light microscopy and transmission and scanning electron microscopy. The epithelium is formed of basal, ciliated, endocrine and secretory cells. It shows different thickness and distribution of the cells, depending on the area (covering the cartilaginous or the membranous zone). Secretory cells show a morphology similar to that found in lizards but it is different from the mucous cells reported in the extrapulmonary airways of turtles, birds and mammals. The ultrastructure of the secretory cells is similar to that reported for serous cells in the airways of mammals. Intra-epithelial plasma cells are also found within the epithelium. The present results show that there are marked morphological differences between the tracheal epithelium of lizards and snakes and that of turtles, birds and mammals. PMID- 2272907 TI - Morphometric analysis of the supraoptic nucleus in the human brain. AB - The supraoptic nucleus (SON) in the human hypothalamus is an elongated, densely packed collection of large neurosecretory cells. The size, shape and cellular morphology of the dorsolateral part of the SON was examined in relation to sex and age in adult subjects. In this region, the following parameters were measured: length of the rostrocaudal axis, maximum cross-sectional area, volume, numerical cell density, total cell number and the mean diameter of the cell nuclei. No sexual differences were observed in any of these parameters with the exception that males have a more elongated SON than females. In contrast to absolute size, sex-linked differences were found in the way the morphometric parameters are interrelated. Of the parameters investigated, only the number of cells in the SON showed significant changes with ageing. A striking increase in the total number of cells, by about 30%, was found between 40 and 65 years of age. A further increase in cell number was observed after the age of 65 years, as a result of which the nucleus contained, on average, 1.4 times as many cells in old subjects (65-90 years) as in young individuals (20-40 years). These findings suggest that a substantial proliferation of glial cells takes place in the human supraoptic nucleus with advancing age. Finally, the morphology of the SON was compared with that of other hypothalamic regions--the suprachiasmatic nucleus (SCN) and the paraventricular nucleus (PVN)--using the same material as that used in previous investigations in this series (Hofman et al. 1988; Hofman & Swaab, 1989). PMID- 2272909 TI - Histological studies on the triangular fibrocartilage complex of the wrist. AB - The triangular fibrocartilage complex of the wrist was serially sectioned for routine histology. Results from eight dissecting room cadavers show that the complex is attached to hyaline cartilage on the radius via its articular disc. In contrast, the dorsal and volar radio-ulnar ligaments attach to the radius via zones of calcified and uncalcified fibrocartilage. The articular disc is thus a wide labrum that provides an articular surface for the ulna and for the carpal bones, and the radio-ulnar ligaments strengthen the attachment of the disc to the radius. Medially, the complex divides into upper and lower laminae. Arching strands of collagen fibres emerge from the upper lamina and pass through a region of highly vascular connective tissue to be attached to the ulna between the articular cartilage on the head and that at the tip of the styloid process. Much of the ulnar attachment is via zones of calcified and uncalcified fibrocartilage which blend with the adjacent articular cartilages. Such an arrangement of tissues prevents undue wear and tear at the ulnar attachment zone during pronation and supination of the forearm. The lower lamina blends with the sheath of extensor carpi ulnaris and the ulnar collateral ligament and allows the whole complex to attach to the carpal and metacarpal bones. The meniscus homologue is a region of dense irregular connective tissue with no independent histological identity. PMID- 2272910 TI - Fine vascular anatomy of adult rabbit knee ligaments. AB - The microvascular anatomy of discrete knee ligaments in adult rabbits is described. Epiligamentous plexuses give rise to a limited number of vessels which penetrate deeply into ligament substance. Intraligamentous vessels are usually longitudinally orientated, widely separated linear anastomoses but occasionally complex glomus-like configurations are present. The significance of these findings is discussed in relation to other articular connective tissues and to the possible roles of the intraligamentous microvasculature. PMID- 2272911 TI - Antibiotic SB22484: a novel complex of the aurodox group. I. Taxonomy of the producing organism, isolation of the antibiotics and chemical and biological characterization. AB - Antibiotic SB22484 is a novel member of the aurodox type antibiotic group produced in submerged-fermentation cultures of Streptomyces sp. NRRL 15496. The antibiotic complex is composed of two pairs of isomers with MW's of 752 and 766. The individual isomers, which were separated by preparative HPLC, equilibrate to a mixture of the isomer pair when left in aqueous solution. In vitro, SB22484 antibiotics strongly inhibited neisseriae and were also active against Streptococci, Ureaplasma urealyticum and Haemophilus influenzae. PMID- 2272912 TI - Antibiotic SB22484: a novel complex of the aurodox group. II. Structure elucidation of the four factors. AB - SB22484, active against Neisseriae gonorrhoeae and Neisseriae meningitidis, is a complex of four factors, designed 1 through 4, which from two pairs of isomers, 1 and 3, and 2 and 4. Factors 1 and 3 account for 65% of the complex, factor 3 being the predominant one. On the basis of the existing and implemented correlations between structure and physico-chemical characteristics (UV and IR spectroscopies, ionization properties, MS as FAB and as negative and positive CI, 1H NMR spectroscopy as 2D COSY and NOESY) in the aurodox field, the complete structures were assigned. Factor 3 can be described as N-[7-[5(R)-[7-[1,2-dihydro 4-hydroxy-1H-2-oxo-3-pyridinyl]-6-methyl- 7-oxo-1(E),3(E),5(E) heptatrienyl]tetrahydro-3(S),4(R)-dihydrox yfuran-2 (S)-yl]-6(S)-methoxy-5,7(R) dimethyl-2(E),4(E)-heptadienyl]-alpha (S)-methyl-5(S)-methyltetrahydro-2(S),4(S or R)-dihydroxy-6(S)-[1(E), 3(Z)-pentadienyl]-2H-pyran-2-acetamide. Factor 1 is an epimer of factor 3 with the opposite configuration at the anomeric center. Factors 2 and 4 have an ethyl group instead of the methyl group alpha to the acetamide moiety and are in the same stereochemical relationship as the pair 1 and 3. PMID- 2272913 TI - Pradimicins M, N, O and P, new dihydrobenzo[a]naphthacenequinones produced by blocked mutants of Actinomadura hibisca P157-2. AB - Four blocked mutants which accumulated new dihydrobenzo[a]naphthacenequinone metabolites, designated pradimicins M, N, O and P, have been isolated from cultures of mutants of Actinomadura hibisca P157-2 resulting from treatment with N-methyl-N'-nitro-N-nitrosoguanidine. The structures of the four compounds were determined by spectral analysis. Pradimicins N, O and P contain D-alanine, while pradimicin M does not. The conformations at C-5 and C-6 of these compounds are different from those of the original pradimicins. PMID- 2272914 TI - Novel antinematodal and antiparasitic agents from Penicillium charlesii. I. Fermentation, isolation and biological activity. AB - Paraherquamide and six novel analogs were isolated from the fermentation of Penicillium charlesii (ATCC 20841). All seven natural products displayed potent antinematodal activity against Caenorhabditis elegans. None of the novel analogs were more potent than paraherquamide. PMID- 2272915 TI - Novel antinematodal and antiparasitic agents from Penicillium charlesii. II. Structure determination of paraherquamides B, C, D, E, F, and G. AB - Paraherquamides B (2, C27H33N3O4), C (3, C28H33N3O4), D (4, C28H33N3O5), E (5, C28H35N3O4), F (6, C28H35N3O3), and G (7, C28H35N3O4) are novel metabolites of Penicillium charlesii. The structures of these compounds have been determined by NMR and MS analysis. PMID- 2272916 TI - WS-7528, a new isoflavanone with estrogen activity isolated from Streptomyces sp. No. 7528. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. AB - WS-7528, produced by Streptomyces sp. No. 7528, was extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as pale yellow powder (C16H14O5, mp 95-98 degrees C). WS-7528 inhibited estrogen binding to its receptor protein in rat uterine cytosol. The IC50 value of WS-7528 for partially purified rat uterine cytosol receptor was 5.7 x 10(-8) M. This compound was found to induce the growth of the estrogen dependent cell line MCF-7. WS-7528 was tested orally and subcutaneously in immature rats to confirm its effect on the growth of the uterus. WS-7528 has also weak anti-inflammatory activity on the carrageenin paw edema of the rat model. PMID- 2272918 TI - The structure of PA48009: the revised structure of duramycin. AB - PA48009, a lanthionine-containing peptide antibiotic was isolated from the culture broth of Streptoverticillium griseoverticillatum PA-48009, and identified as duramycin. Determination of the structure using both Edman degradations and 2D NMR spectroscopy showed the need to revise the structure of duramycin given in literature. Duramycin (PA48009) was different from lanthiopeptin (Ro 09-0198, cinnamycin) only by a Lys/Arg exchange at position 2. PMID- 2272917 TI - Antibiotics from basidiomycetes. XXXVII. New inhibitors of cholesterol biosynthesis from cultures of Xerula melanotricha Dorfelt. AB - Three new inhibitors of cholesterol biosynthesis have been isolated from cultures of Xerula melanotricha and their structures elucidated by spectroscopic methods. Dihydroxerulin (1) in admixture with xerulin (2) strongly inhibits the incorporation of 14C- acetate into cholesterol in HeLa cells while the incorporation of 14C-mevalonate is not affected. Xerulinic acid (3) shows similar biological activities but a higher cytotoxicity. PMID- 2272919 TI - Secondary metabolites by chemical screening. 7. I. Elaiophylin derivatives and their biological activities. AB - The synthesis and the biological activity of 34 acyl derivatives of elaiophylin (1) and 6 deglycosidation products were described. Especially the unsymmetric deglycosidation products 33, 38 and 40 and dimethyloctahydroelaiophylin (21) exhibited an activity against nematodes. PMID- 2272920 TI - Synthesis and biological properties of 1-oxapenems. AB - Several 2-substituted oxapenems, 1a, 1b and 1c, bearing the hydroxyethyl side chain at 6 alpha were synthesized in a highly stereoselective manner starting from the commercially available 3 alpha-hydroxyethyl-4 beta-acetoxyazetidinone (5). The stability, in vitro antibacterial activity, and beta-lactamase inhibitory properties of these oxapenems were examined. The 2-isopropyl penem 1c had considerable stability as shown by its t1/2 of 200 minutes in pH 7.0 buffer solution and at 37 degrees C, while the other two 1a and 1b were labile. Interestingly, the antibacterial activity of these compounds paralleled their stability and thus penem 1c showed appreciable MICs, whereas the other two were virtually inactive. All three penems inhibited certain cephalosporinases strongly, but penicillinases only weakly. Thus, the inhibitory spectrum was similar to that for epi-thienamycin B and not the spectrum for clavulanic acid. PMID- 2272921 TI - Improved antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin. AB - The preparation and antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin are described. Di-N-alkylation of pirarubicin with bis(2 iodoethyl)ether gave 3'-morpholino-pirarubicin, which was converted into its 13 tosylhydrazone, 13-deoxy derivative and 13-(S)- and 13-(R)-dihydro derivatives. Intraperitoneal administration to murine tumors indicated that the effective dose ranges of the compounds having sp3 carbon at C-13 position were broader than those of the compounds having sp2 carbon. By oral administration, 13-(S)-dihydro isomer was more effective than 13-(R)-dihydro isomer. PMID- 2272922 TI - Carboxyhydrazides of the aglycone of teicoplanin. Synthesis and antibacterial activity. AB - The condensation of the terminal carboxyl group of the deglucoteicoplanin (TD) with various substituted hydrazines produced hydrazide derivatives having different physico-chemical properties. This chemical modification of the carboxyl function does not affect the ability of teicoplanin antibiotics to interfere in bacterial cell-wall synthesis. The antibacterial activity of deglucoteicoplanin hydrazides (V) were found to depend mostly on their ionic character. All the hydrazides were slightly more active than TD on Escherichia coli. Those possessing an additional basic group were more in vitro active than TD against Gram-negative microorganisms. In Experimental Streptococcus pyogenes septicemia in the mouse, basic hydrazides were more active than other derivatives when administered subcutaneously although they are as potent as TD. PMID- 2272923 TI - Screening of antibiotics preferentially active against ras oncogene-expressed cells. AB - During the course of in vitro screening of agents which are preferentially active against ras oncogene-expressed cells, a new anthracycline (identified as 2 demethylsteffimycin D) and a heptaene (possibly a new member of partricins) were isolated from microbial fermentation broths. Among known compounds tested, 5 fluorouracil, 5-fluorodeoxyuridine and oxanosine showed high selectivity towards ras oncogene-expressed cells. PMID- 2272924 TI - Novel macrolides from Micromonospora rosaria. PMID- 2272925 TI - Use of resins for trichothecene production in liquid cultures. PMID- 2272926 TI - Cytogenin, a novel antitumor substance. PMID- 2272927 TI - Biosynthesis of mycinamicins by a blocked mutant of Micromonospora griseorubida. PMID- 2272928 TI - The effect of interaural phase on frequency discrimination with broad- and narrow band maskers. AB - With both broad-band and narrow-band noise maskers there is a small range of signal-to-noise ratios where, with the maskers in-phase and signals 180 degrees out-of-phase at the ears, detection performance grows with increasing signal-to noise ratio but frequency discrimination performance does not. The observation may have significant consequences for our understanding of the way in which frequency is coded at low signal-to-noise ratios. PMID- 2272929 TI - The effect of signal duration on frequency discrimination at low signal-to-noise ratios in different conditions of interaural phase. AB - Frequency discrimination in noise at low signal-to-noise ratios where the signals to be discriminated are equally well detected but only faintly audible is better when the signals are in-phase at the ears than when they are out-of-phase. In spite of the difference in discriminability, however, the form of the dependence of the just-noticeable frequency difference on signal duration is the same in both cases. PMID- 2272930 TI - Electrophysiological aspects of the middle ear muscle reflex in the rat: latency, rise time and effect on sound transmission. AB - The latency, the rise time and the influence of the acoustic reflex on sound transmission were investigated in the adult rat during ketamin anesthesia. This was done by recordings of the cochlear microphonics (CM) and electromyographic (EMG) recordings of the reflex responses of the tensor tympani muscle. The acoustic reflex was elicited by contralateral acoustic stimuli of which the intensity and frequency was varied. Ipsilaterally, the effect on sound transmission was determined by estimating the change in amplitude of the CM's of ipsilateral administered subliminal stimuli. It was shown that both the tensor tympani muscle and the stapedius muscle contribute in the reflex. The latency as well as the rise time of the reflex determined by CM recordings showed to be short (minimal values: 12 and 7 ms respectively). The mean latency of the tensor tympani muscle reflex, measured by EMG, was about 7 ms. The attenuation of 0.25-8 kHz tone bursts upto 115 dB SPL is limited to a mean maximum of 15 dB SPL. The maximal attenuation was shown to occur at 1 kHz. Frequencies above 2 kHz appeared to be the best elicitor of the middle ear muscle reflex. PMID- 2272931 TI - Different phase sensitivity of low- and high-frequency neurons from the cat's cochlear nucleus. AB - When tested with two-tone signals while varying the phase value (omega 2) of the second harmonic, the low-frequency neurons (CFs from 0.8 to 5 kHz) showed one maximum and one minimum of the response value over the omega 2-range of 360 degrees. The high-frequency neurons (CFs from 11.5 to 38.5 kHz) showed two maxima and two minima under the same conditions. In addition, the high-frequency neurons, unlike the low-frequency ones, showed no difference in response to click series of opposite polarities. The data are considered in connection with processes of excitation in the low- and high-frequency regions of the cochlea. PMID- 2272932 TI - Hearing in domestic pigs (Sus scrofa) and goats (Capra hircus). AB - Behavioral audiograms were determined for three pigs and two goats. The hearing of the pigs ranged from 42 Hz to 40.5 kHz with a region of best sensitivity from 250 Hz to 16 kHz. Hearing in goats ranged from 78 Hz to 37 kHz with a well defined point of best sensitivity at 2 kHz. Because these animals are unable to localize high-frequency tones, it seems unlikely that selective pressure to use the interaural spectral-difference cue for sound localization is behind their high-frequency hearing. Instead, we suggest that these and other hoofed mammals evolved high-frequency hearing in order to use monaural locus cues which prevent front/back locus reversals. PMID- 2272933 TI - Histochemistry of otic capsule sclerotic lesions in Palmerston North autoimmune strain mice. AB - Otic capsule osteogenesis is a common finding in temporal bones from autoimmune disease individuals. However, the underlying cellular mechanisms are poorly understood. Therefore, to better understand this relationship of autoimmune disease and otic capsule pathology, inner ear sclerotic lesions of the Palmerston North autoimmune disease mouse were histochemically stained to identify their content and potential osteogenic processes. Lesions stained positive for calcium, amyloid, fibrinoid, and glycoproteins (PAS), but negative for collagen, calcium oxalate, reticular fibers and glycosaminoglycans (Alcian Blue). Amyloid and fibrinoid deposition are associated with other immune disease, which suggests these local processes may provide a protein substructure that calcifies in lesion progression. Similar cellular mechanisms may underlie certain types or phases of human autoimmune otic capsule disease. PMID- 2272934 TI - Spontaneous and electrically induced movements of ampullary kinocilia and stereovilli. AB - In the transparent vestibular organ of young eels, isolated in toto, movements of individual kinocilia and hair bundles of the frontal ampulla were recorded by photodiodes and a video system. Flagella-like oscillations of kinocilia occurred spontaneously when preparations deteriorated and could be induced regularly in fresh preparations by pressing onto the tip of the cilium. Upon step-like electrical polarization of the epithelium hair bundles deflected in a tonic, pointer-like manner. When the apical membrane was hyperpolarized the hair bundles deflected towards the kinocilium (positive deflection) amounting to about 0.6 degrees when the polarization was made strong enough to cause saturating responses in the ampullary nerve. In response to sinusoidal voltage the amplitude of the hair bundle deflection declined by -4 dB/octave for frequencies above 1.3 Hz. When the kinocilium was disconnected from the bundle of stereovilli by transient reduction of divalent cations, voltage induced deflections occurred, of both the kinocilium and the stereovilli. Reducing the extracellular Ca-activity seemed to destabilize the electrically induced deflections; blocking the oxidative metabolism (CN-) had no effect. The induced deflections only disappeared upon chemical fixation by glutaraldehyde or treatment with triton X 100. Surface tension and electrostriction of the cell membrane are discussed as possible force generators. PMID- 2272935 TI - Acoustic isolation reduces degeneration of the ventral cochlear nuclei in Mongolian gerbils. AB - The role of auditory experience in the development of spongiform degeneration in the cochlear nuclei of Mongolian gerbils was studied by comparing results of animals exposed to either high or low levels of ambient noise. Gerbils reared in a typical vivarium experienced higher levels of ambient noise than animals reared in acoustic isolation chambers. Animals reared in the colony room showed a much greater number density and area density of spongiform lesions in the CN than did gerbils reared in acoustic isolation. The differences in the number and extent of spongiform lesions between the two groups of gerbils appeared to reflect their differences in exposure to ambient noise. These differences in lesion number and extent were most pronounced in the tonotopic regions of the PVCN which correspond to the greatest differences in the spectral characteristics of the ambient noise to which the animals were exposed. These results were compared with results previously obtained from gerbils with loss of hearing experimentally induced by a conductive block or by sensorineural damage. The lesion numbers and extent reflected the auditory experience of each group; in descending order, colony reared, isolate, conductive-block, sensorineural loss. These results strongly support the hypothesis that this gerbilline encephalopathy is directly related to auditory functional activity. PMID- 2272936 TI - Dietary restriction slows the abnormally rapid loss of spiral ganglion neurons in C57BL/6 mice. AB - Dietary restriction as a means extending the life span and exploring the aging process has interested researchers for over 50 years. We wanted to determine whether dietary restriction would alter the unusually rapid aging of the auditory ganglion in the C57BL/6NNia mouse. Quantitative methods were used to estimate the number of spiral ganglion neurons in the cochleas of 18 month-old dietary restricted and ad libitum-fed C57BL/6NNia mice. The number of spiral ganglion neurons in dietary restricted mice was significantly higher than those on an ad libitum diet. This is the first study to quantitatively demonstrate that severe neuron loss in the auditory ganglion of a mouse suffering inherited, prepubertal deafness can be slowed by caloric restriction. PMID- 2272937 TI - Hypersensitivity of hydropic ears, at frequencies with normal thresholds, to temporary threshold shifts. AB - We have shown that experimentally-induced hydrops in the guinea pig systematically provokes an early low frequency (6.4 kHz and below) fluctuant hearing loss. The present study was aimed at investigating one aspect of the functioning of that part of the audiogram with normal CAP thresholds (mid and high frequencies) in early hydrops. Temporary threshold shifts (TTS) as a function of pure tone stimulation level (8 kHz, 1 min 75-95 dB SPL), were investigated. The TTS was measured as a function of pure-tone exposure level. The different points on the input/output curve were determined on sequential days in order to allow full recuperation from the previous stimulation. The group of hydropic ears (N = 5) proved to be more sensitive by about 6 dB than the group of control ears (N = 10). The data indicate that whilst short-term endolymphatic hydrops can be characterised by a selective low frequency loss other auditory deficits exist throughout the cochlea and become manifest at supraliminal stimulus levels. PMID- 2272938 TI - Binaural interaction in a cochlear implant patient. AB - Binaural interaction was demonstrated in electrically evoked brainstem responses (EBRs) of a bilaterally implanted patient. A clear binaural difference waveform (BD), consisting of a negative peak near 3.6 ms followed by a positive peak near 4.4 ms, was found by subtracting the recordings with diotic stimulation from the sum of the recordings with monotic stimulation. These results are consistent with those reported for normal subjects and suggest that neural processing in this patient might resemble those ordinarily used in binaural hearing. They strengthen the argument that EBRs in cochlear implant patients do result from activity in auditory brainstem neurons and suggest a method for aligning the positions of the intracochlear electrodes. PMID- 2272939 TI - Seasonal variation of thermophilic campylobacters in sewage sludge. AB - The seasonal variation of thermophilic campylobacters in Lancaster's sewage sludge was studied over a 21 month period. The numbers in fresh sludge (from primary sedimentation) vary between approximately 200 and 5000/100 ml for most of the year but there was a large increase in May and June (in May 1988 there were 42,100 campylobacters/100 ml which is 17 times more than in the preceding April). In 1989 there was a similar May/June peak but with lower numbers. This seasonal variation, measured by environmental monitoring, reflects the incidence of infections in the community. The same pattern was found in 2-d old sludge but the numbers were substantially lower (40% lower over the experimental period). Thermophilic campylobacters were virtually absent from digested sludge and sludge prior to land distribution. Survival experiments confirm that campylobacters survive for only a few hours in both sterile and unsterile digested and undigested sludge. These results suggest that it is safe to dispose of Lancaster's digested sludge on land but there is still uncertainty about the ability of campylobacters to survive in sludge in the viable but non-culturable form. PMID- 2272940 TI - The effect of physical and microbiological factors on food container leakage. AB - The effect of physical and microbiological factors on food container leakage was investigated in a container leakage model system (CLMS). The leakage of Acinetobacter calcoaceticus, Staphylococcus sp., Pseudomonas sp., Bacillus sp., a coryneform, Staph. aureus, and two biotest organisms (Enterobacter cloacae NC1B 8151 and Ent. aerogenes MB31) was studied. The rate of bacterial leakage (log10 cells/channel/s) was greater in the presence of a partial vacuum of 51-305 mm Hg than at atmospheric pressure. Fluid flow (ml) through leakage channels was increased by the application of vacuum. Leakage varied with vacuum, bacterial morphology, cell concentration, leakage channel size (0.78-120 micron 2) and channel shape (straight or convoluted). The number of leaked cells was not proportional to vacuum or channel size. The effect of channel shape varied with bacterial species. Increased container medium viscosity decreased bacterial leakage. Fluid flow through leakage channels was generally reduced by the most viscous solution. Cells from biofilms and monolayers of Ac. calcoaceticus or Staph. aureus attached to nylon (Hyfax) or stainless steel surfaces underwent leakage. Mixed bacterial populations had characteristic leakage rates against vacuum different from the leakage pattern of individual species in the population. The composition of the leaked population was different from the original inoculum. The results indicated that container leakage is a complex process involving a range of interdependent factors. PMID- 2272941 TI - A model system for the study of food container leakage. AB - A model system to study food container leakage was developed. The model system allows the independent investigation of the effect of physical factors such as vacuum and contents viscosity, and microbial factors on the leakage process. The design, construction and operation of the container leakage model system is described. PMID- 2272942 TI - Antigenic property of pediocin AcH produced by Pediococcus acidilactici H. AB - Pediocin AcH, a bacteriocin of Pediococcus acidilactici H, inhibits the growth of several food spoilage and pathogenic bacteria. The antigenic property of partially purified pediocin AcH was tested by immunizing mice and a rabbit. Pediocin AcH was not immunogenic in these animals as determined by immunoblotting even after conjugation to bovine serum albumin. The non-immunogenic nature of pediocin AcH, its non-toxicity to laboratory animals and its hydrolysis by gastric proteolytic enzymes may be considered favourably in its possible use as a food preservative. PMID- 2272943 TI - Preliminary development of a diagnostic test for Brucella using polymerase chain reaction. AB - A highly sensitive and specific diagnostic test for Brucella based on polymerase chain reaction is under development in our laboratory. A commercially available PCR kit was used to create primers that allowed the amplification of a 635 bp fragment of a 43 kDa outer membrane protein gene from Brucella abortus strain 19. We successfully amplified the cloned gene present in the pMS64 plasmid and genomic Brucella S19 DNA. The amplified DNA was easily detected by agarose gel electrophoresis. Using both the pMS64 plasmid and Br. abortus S19 purified DNA as template each component of the PCR reaction was adjusted for the optimum amplification of the DNA sequence. Optimum specific amplification resulted when the primer annealing temperature was 60 degrees C. The gene fragment was amplifiable in 25 different Brucella species and strains. To test the specificity of the reaction, DNA extracted from 17 micro-organisms possibly associated with cattle were tested. No amplification was observed. The sensitivity of the reaction was determined with different concentrations of genomic Brucella strain 19 DNA. As little as 0.1 pg DNA (less than 100 brucella cells) could be detected. The specificity and sensitivity of PCR combined with its simplicity and speed suggests the potential of this technique for routine diagnosis of brucellosis. PMID- 2272944 TI - Effect of minocycline on subgingival plaque bacteria. AB - The effects of minocycline on subgingival plaque samples from patients with chronic periodontitis were investigated in vitro. Minocycline concentrations as low as 1.0 microgram/ml inhibited 95.7% of the cultivable bacteria in the samples but 256 micrograms/ml was necessary to inhibit all of the cultivable bacteria in the samples. Although up to 99.9% of bacteria in the plaque samples were killed by a 6 h exposure to 8.0 micrograms/ml of minocycline, large numbers of viable bacteria remained. These results imply that adequate reductions in the numbers of viable subgingival plaque bacteria are unlikely to occur after exposure to minocycline at concentrations attainable in gingival crevicular fluid after systemic administration. PMID- 2272945 TI - Correlation between environmental monitoring of thermophilic campylobacters in sewage effluent and the incidence of Campylobacter infection in the community. AB - Environmental monitoring of thermophilic campylobacters in liquid sewage effluent (primary settlement only) during 1988 and 1989 showed a prominent seasonality with distinct peaks in May and June (the average number of bacteria per 100 ml of effluent in months other than May and June was 2244 and the average for the peak months was 50,778). Apart from September 1989, this seasonality coincided precisely with the seasonal variation of campylobacter enteritis in the community with similar distinct peaks in May and June (the incidence of infection in May and June was twice or three times that in the other months). Sampling of sewers showed that the campylobacters in the sewage effluent came mainly from abbatoir and animal processing plants with only a minor input from the community. Therefore, the seasonal peaks in the sewage effluent and in the community may not be dependent on human infections but on zoonotic infections which may also peak in May and June. PMID- 2272946 TI - Microbial transformation of styrene by anaerobic consortia. AB - Methanogenic microbial consortia, originally enriched from anaerobic sewage sludge with ferulic acid or styrene (vinylbenzene) as sole organic carbon and energy sources, were used to study transformation of styrene under strictly anaerobic conditions. Styrene, which was added as the substrate in a range of concentrations from 0.1 to 10 mmol/l, was extensively degraded but no methane production was observed during incubation for eight months. The addition of yeast extract during the enrichment stage completely inhibited degradation of styrene. Gas chromatography (GC), gas chromatography/mass spectrometry (GC/MS), high performance liquid chromatography (HPLC) analyses of the culture fluid, and GC analyses of the anaerobic headspace, indicated that the transformation of this arylalkene was initiated through an oxidation-reduction reaction and that the favoured mechanism was most likely the addition of water across the double bond in the alkenyl side-chain. The degradation proceeded through to carbon dioxide, the final product. Benzoic acid and phenol were transient compounds found in highest concentrations in the spent culture fluid and are suggested as the key intermediates of the transformation process. The tentative routes of anaerobic transformation partially overlap with those previously proposed for aromatic hydrocarbons such as toluene. Several pure cultures, which were tentatively identified as Clostridium spp. and Enterobacter spp., were isolated from the styrene-degrading consortia. Two of these cultures were demonstrated to grow on styrene as sole carbon and energy source. Additionally, a pure culture of Enterobacter cloacae DG-6 (ATCC 35929) which had been isolated previously from the ferulate-degrading consortium, was shown to degrade styrene through to carbon dioxide. PMID- 2272947 TI - World War II and respiratory physiology: the view from Rochester, New York. PMID- 2272948 TI - Lipase regulation of muscle triglyceride hydrolysis. AB - The cellular control of intramuscular triglyceride (TG) metabolism involves two major identified lipases: hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). Recently, the presence of HSL in muscle has been unequivocally demonstrated. However, although it is thought that HSL is responsible for intramuscular TG lipolysis, direct evidence for this is lacking. There is evidence to suggest that HSL and LPL are simultaneously activated under a variety of conditions. The two muscle lipases appear to be turned on by the same signal and function as a coordinated unit in meeting the energy demands of muscle. At a time when HSL is presumably hydrolyzing endogenous TG, LPL is sent to the capillary beds in search of substrate. TG uptake from circulation is highly related to muscle LPL activity. Exercise training increases LPL activity in plasma and in parenchymal cells in muscle. These results suggest that training may increase the capacity to clear TG from circulation and that LPL might have a role in replenishing muscle TG stores that have been decreased with exercise. PMID- 2272949 TI - Distribution of blood flow during exercise after blood volume expansion in swine. AB - To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition. PMID- 2272950 TI - Hemodynamic responses during exercise at and above VO2max in swine. AB - Mean arterial pressure (Pa), heart rate, cardiac output (Q), and Q distribution (with radiolabeled microspheres) were measured in miniature swine as they ran at high levels on a motor-driven treadmill. Each animal ran on two occasions: once during exercise at maximal O2 uptake (VO2max) and once at an intensity estimated to require approximately 115% VO2max. The purpose was to assess these cardiovascular variables to determine whether the calculated resistance to blood flow during supramaximal exercise was different from that during maximal exercise. A total of 114 tissues/organs were dissected for blood flow analysis. Pa and Q were unaltered between the two exercise conditions. Blood flow to all but one of the 62 skeletal muscles sampled was unchanged between conditions as were the blood flows to the visceral organs and brain. The results demonstrate that vascular resistance was constant in all these tissues between maximal and supramaximal exercise intensities. Elevated blood flows were measured in 7 of the 11 coronary sites sampled. Calculated resistance to blood flow indicated that a decrease in resistance occurred in most of the samples having elevated blood flow. Because heart rate was elevated during the supramaximal exercise, the increase in blood flow was probably in response to the greater myocardial work and concomitant elevation in O2 demand. In summary, it was shown that Pa, Q, and Q distribution in most tissues remained unchanged during exercise at intensities above VO2max. Thus a precise matching occurs between the increasingly powerful vasoconstrictor drive initiated by the sympathetic nervous system and the elevated local vasodilatory drive responding to the greater O2 demand during the supramaximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272951 TI - Nonadrenergic inhibitory nerves attenuate neurally mediated contraction in cat bronchi. AB - Effects of nonadrenergic and noncholinergic (NANC) inhibitory nerves on cholinergic neurotransmission were examined in isolated bronchial segments from cats in the presence of propranolol (10(-6) M) and indomethacin (10(-6) M) by use of electrical field stimulation (EFS) techniques. EFS caused contraction alone in tissues at the baseline tension and biphasic responses (contraction and relaxation) in tissues precontracted with 5-hydroxytryptamine. Contraction was abolished by atropine (10(-6) M), and relaxation was abolished by tetrodotoxin (10(-6) M). At the baseline tension, EFS at frequencies greater than 10 Hz inhibited the subsequent (4 min later) contraction induced by EFS at 1-5 Hz. EFS induced inhibition was stimulus frequency dependent and reached maximum at 20 Hz. However, EFS at 20 Hz did not inhibit the subsequent contractile response to acetylcholine (10(-7) to 10(-3) M). Exogenously applied vasoactive intestinal peptide mimicked EFS-induced inhibitory effects, but substance P and calcitonin gene-related peptide did not. The inhibitory effect of EFS at 20 Hz was not altered by pyrilamine, cimetidine, naloxone, methysergide, phentolamine, BW755C, AF-DX 116, or removal of epithelium. These results imply that the NANC transmitter acts via presynaptic cholinergic receptors. PMID- 2272952 TI - Thrombin's enzymatic activity increases permeability of endothelial cell monolayers. AB - Human alpha-thrombin increases the permeability of bovine pulmonary artery endothelial cell (CCL-209) monolayers. To determine if this increase is via an enzymatic or receptor-mediated mechanism, enzymatically active forms of alpha thrombin and enzymatically inactive forms with cell binding activity were incubated with the monolayers. Enzymatic forms included alpha-thrombin and two digestion products, zeta-thrombin (chymotryptic product with 89% clotting activity) and gamma-thrombin (tryptic product). Enzymatically inactive forms included D-Phe-Pro-Arg-chloromethylketone-(PPACK) alpha-thrombin and diisopropylphosphorofluoridate-(DIP) alpha-thrombin. Cell binding activity of alpha- and PPACK-alpha-thrombin was demonstrated to be similar to each other and comparable to that cited in the literature for DIP-alpha-thrombin. gamma Thrombin, on the other hand, did not compete for binding of 125I-labeled alpha thrombin. All enzymatic forms of alpha-thrombin increased endothelial permeability as assessed by the clearance of 125I-albumin across the monolayers. Coincubation of PPACK, an enzymatic site inhibitor, with alpha- or gamma-thrombin prevented the increase in permeability, further indicating that alpha-thrombin increased permeability by its enzymatic activity. Both enzymatically inactive forms of alpha-thrombin with high-affinity binding activity had no effect on permeability. To further examine whether cell binding activity of alpha-thrombin contributed to the increased permeability, a sulfated COOH-terminal fragment of hirudin (hirugen) that binds to the anion-binding site of alpha-thrombin but, unlike hirudin, does not interact with the catalytic site was coincubated with alpha-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272953 TI - Coordination of breathing, sucking, and swallowing during bottle feedings in human infants. AB - Incoordination of sucking, swallowing, and breathing might lead to the decreased ventilation that accompanies bottle feeding in infants, but the precise temporal relationship between these events has not been established. Therefore, we studied the coordination of sucks, swallows, and breaths in healthy infants (8 full-term and 5 preterm). Respiratory movements and airflow were recorded as were sucks and swallows (intraoral and intrapharyngeal pressure). Sucks did not interrupt breathing or decrease minute ventilation during nonnutritive sucking. Minute ventilation during bottle feedings was inversely related to swallow frequency, with elimination of ventilation as the swallowing frequency approached 1.4/s. Swallows were associated with a 600-ms period of decreased respiratory initiation and with a period of airway closure lasting 530 +/- 9.8 (SE) ms. Occasional periods of prolonged airway closure were observed in all infants during feedings. Respiratory efforts during airway closure (obstructed breaths) were common. The present findings indicate that the decreased ventilation observed during bottle feedings is primarily a consequence of airway closure associated with the act of swallowing, whereas the decreased ventilatory efforts result from respiratory inhibition during swallows. PMID- 2272954 TI - Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation. AB - Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2 7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure. PMID- 2272955 TI - Quantitative autoradiographic assessment of 55Fe-RBC distribution in rat brain. AB - A simple in vivo technique of labeling erythrocytes (RBCs) with 55Fe was developed for quantitative autoradiography (QAR). This procedure involved injecting 5-6 ml of [55Fe]ferrous citrate solution (1 mCi/ml) intraperitoneally into donor rats. The number of labeled RBCs reached a maximum at around 7 days and declined very slowly thereafter. Labeled RBCs were harvested from donor rats and used for RBC volume measurement in awake rats. Brain radioactivity was assayed by QAR, which yielded spatial resolution of greater than 50 microns. Tight nearly irreversible binding of 55Fe to RBCs was found in vivo and in vitro. More than 99.5% of the 55Fe in the blood of donor rats was bound to RBCs. Because of this, labeled blood can be taken from donors and injected into recipients without further preparation. The tissue absorption of 55Fe emissions was the same in gray and white matter. Microvascular RBC volumes measured with 55Fe-labeled RBCs agreed with those assayed with 51Cr-labeled RBCs for many, but not all, brain areas. In conclusion, 55Fe-RBCs can be readily prepared by this technique and accurately quantitated in brain tissue by QAR. PMID- 2272956 TI - Plasma fibronectin levels during cardiopulmonary bypass. AB - Plasma fibronectin, also called cold-insoluble globulin, is a cryoprecipitable glycoprotein with both opsonic and adhesive activities. It binds to collagen, actin, and heparin and can form soluble as well as cryoprecipitable complexes in the cold. Fibronectin augments particulate phagocytosis by the reticuloendothelial system and can influence lung vascular permeability. Plasma fibronectin deficiency is temporally associated with respiratory failure in septic surgical, trauma, and burn patients. We measured plasma fibronectin and albumin levels in nine adults undergoing elective cardiopulmonary bypass to determine whether dilution alone could account for the changes in plasma fibronectin. Plasma fibronectin concentration decreased 17% with the surgical trauma of opening of the chest and placement of the vascular cannulas. On heparinization and initiation of cardiopulmonary bypass, plasma fibronectin fell an additional 48% (P less than 0.001), whereas albumin concentration (corrected for albumin in the pump prime) fell only 25% (P less than 0.001), emphasizing that dilution was not the only mechanism contributing to the decline in plasma fibronectin. Fibronectin levels began to increase after discontinuation of cardiopulmonary bypass and in association with diuresis, but unexpectedly they remained subnormal until 4 days postoperation. Thus the decline in fibronectin concentration with cardiopulmonary bypass may be due to dilution as well as opsonic consumption and possible complexing with heparin in the cold. PMID- 2272957 TI - Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate. AB - The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle. PMID- 2272958 TI - Interaction of chemical and high vascular pressure injury in isolated canine lung. AB - Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure induced (mechanical) injury would be decreased after a chemical insult to the lung. Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O. Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min 1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively. However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05). The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively. However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272959 TI - Impedance measurement during air and He-O2 breathing before and after salbutamol in normal subjects. AB - Total respiratory resistance and reactance from 4 to 52 Hz were determined by the method of forced pseudorandom noise oscillation in 20 normal male subjects before and after inhalation of 0.200 mg salbutamol (albuterol) and before and after the subjects were equilibrated with 80% He-20% O2. During air breathing, there was a statistically significant decrease of resistance values at lower frequencies after inhalation of salbutamol. When the subject was equilibrated with 80% He-20% O2, total respiratory resistance markedly decreased at all frequencies, and a negative frequency dependence of resistance was observed between 8 and 20 Hz. Resistance values further decreased during He-O2 breathing after inhalation of salbutamol. After inhalation of salbutamol, reactance values increased during air and He-O2 breathing. The density-dependent decrease of the real part of impedance can be explained by a decrease of turbulence in the larger airways. The bronchodilating effect of salbutamol was not influenced by a change in the physical properties of the inhaled gas. During He-O2 breathing, reactance values significantly decreased, resulting in an increase of resonant frequency due to a decrease of inductive reactance. It is concluded that an increase in the capacitance of the respiratory system must be supposed to explain the increase in reactance values after inhalation of the beta-adrenergic agonist salbutamol. PMID- 2272960 TI - Cough-enhanced mucus clearance in the normal lung. AB - We studied the effectiveness of cough for clearing mucus in 12 nonsmoking subjects with normal lung function. On 2 separate study days, each subject breathed 6-microns Mass Median Aerodynamic Diameter 99mTc-labeled iron oxide particles under controlled breathing conditions while they were seated in front of a gamma camera. Retention (R) of lung activity was measured over the initial 2 h and again at 24 h after particle inhalation. On the control day the subject sat quietly in front of the camera, while on the cough day each subject performed 60 controlled coughs during the 1st h of retention measurements. By paired analysis, retentions at both 1 and 2 h (R1 and R2, respectively) for the cough measurements were significantly less than control (mean control R1 = 85% vs. mean cough R1 = 72%, P less than 0.002; mean control R2 = 75% vs. mean cough R2 = 65%, P less than 0.02). Retention at 24 h (R24) was not significantly different between cough and control measurements (mean cough R24 = 35% and mean control R24 = 32%). Thus coughing increased the rate at which the radiolabeled particles were cleared from the bronchial airways in these individuals. Follow-up experiments with subjects performing rapid inhalations rather than cough showed similar enhanced particle clearance to that seen with cough. These results suggest that the observed enhancement of mucus clearance by cough (and rapid inhalation) in the normal lung may be due to a stimulation of the mucociliary apparatus rather than via a two phase gas-liquid flow mechanism. PMID- 2272961 TI - Recovery of breathing pattern after 15 min of cerebral ischemia in rabbits. AB - The study was undertaken to ascertain the neural control of breathing and vagal reflexes during and after cerebral ischemia. The experiments were performed on anesthetized, paralyzed, and artificially ventilated rabbits. Cerebral ischemia was induced by reversible intrathoracic occlusion of the brachiocephalic trunk and the left subclavian and both internal thoracic arteries for 15 min. The effect of cerebral ischemia on breathing pattern was assessed by monitoring the integrated activities of phrenic and recurrent laryngeal nerves. Ischemia produced enhancement of breathing followed by apnea and gasping. During enhanced breathing as well as during gasping, the inspiratory-inhibiting effect of lung inflation (Breuer-Hering reflex) was abolished. When brain circulation was restored, respiratory activity started with gasps, which later were intermingled with eupneic type of inspirations. During the onset of a eupneic breath, lung inflation produced inspiratory facilitation but never an inhibition. However, after 30 min of recovery from cerebral ischemia, the Breuer-Hering reflex was restored. Results show that precise analysis of vagal reflexes and respiratory pattern during ischemia and resuscitation may be used as an indicator of resumption of autonomic activity in the brain stem. PMID- 2272962 TI - High-frequency characteristics of respiratory mechanics determined by flow interruption. AB - When flow at the airway opening is suddenly interrupted, the pressure measured just behind the point of interruption generally exhibits certain characteristic features, including some rapid and highly damped oscillations immediately after the interruption. It has previously been assumed that these oscillations reflect ringing of central airways gas. In the present study we investigated this hypothesis by performing flow interruptions during relaxed expiration in normal, tracheostomized, anesthetized, paralyzed dogs while the lungs were filled with four different gas mixtures having widely varying physical properties. We found that the power spectrum of the oscillations exhibited two peaks. The larger peak was centered about a frequency that varied approximately linearly with the inverse of the square root of the gas density. The other peak was smaller and was located at approximately 70 Hz with all gas mixtures. The area under the power spectrum of the ringing varied approximately linearly with the density of the gas mixture. These results indicate that the larger peak in the power spectrum reflects the quarter-wave resonance of the gas in the airways, whereas the smaller peak reflects a tissue resonance. PMID- 2272963 TI - Effect of exercise on glucose disposal: response to a maximal insulin stimulus. AB - We used the euglycemic clamp to assess the effects of exercise on maximally insulin-stimulated glucose disposal. In 11 young men, a 60-min bout of exercise had no significant effect on the rate of glucose disposal during a euglycemic clamp performed approximately 30 min postexercise in which plasma insulin was raised to approximately 2,500 microU/ml (a maximal insulin stimulus). The maximal rate of glucose disposal attained during the clamp averaged 15.7 +/- 1.0 mg.kg lean body mass-1.min-1 after exercise vs. a control value of 15.4 mg.kg lean body mass-1.min-1. In a second experiment, eight men performed supine cycle exercise during the 3rd h of a 4-h euglycemic clamp with a plasma insulin concentration of approximately 2,500 microU/ml. Exercise during the hyperinsulinemic clamp resulted in a 70% increase in glucose disposal rate. There was no measurable increase in glucose 6-phosphate in the quadriceps muscle during the insulin infusion at rest. We conclude that prior exercise does not enhance maximally insulin-stimulated glucose disposal in young healthy men. Our results are compatible with the interpretations that glucose availability rather than glucose metabolism limits the rate of glucose disposal in response to a maximal insulin stimulus in resting subjects and that the increase in glucose uptake in response to superimposed exercise is primarily due to an increase in glucose availability. PMID- 2272964 TI - Effects of body position and lung volume on in situ operating length of canine diaphragm. AB - The performance of the diaphragm is influenced by its in situ length relative to its optimal force-generating length (Lo). Lead markers were sutured to the abdominal surface of the diaphragm along bundles of the left ventral, middle, and dorsal regions of the costal diaphragm and the left crural diaphragm of six beagle dogs. After 2-3 wk postoperative recovery, the dogs were anesthetized, paralyzed, and scanned prone and supine in the Dynamic Spatial Reconstructor (DSR) at a total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV). The location of each marker was digitized from the reconstructed DSR images, and in situ lengths were determined. After an overdose of anesthetic had been administered to the dogs, each marked diaphragm bundle was removed, mounted in a 37 degrees C in vitro chamber, and adjusted to Lo (maximum tetanic force). The operating length of the diaphragm, or in situ length expressed as percent Lo, varied from region to region at the lung volumes studied; variability was least at RV and increased with increasing lung volume. At FRC, all regions of the diaphragm was shorter in the prone posture compared with the supine, but there was no clear gravity-dependent vertical gradient of in situ length in either posture. Because in vitro length-tension characteristics were similar for all diaphragm regions, regional in vivo length differences indicate that the diaphragm's potential to generate maximal force is nonuniform. PMID- 2272965 TI - Positive adaptations to weight-lifting training in the elderly. AB - Maximal weight-lifting performance, isometric strength, isokinetic torque, whole muscle and individual fiber cross-sectional areas, and muscle evoked contractile properties were assessed in 14 elderly males before and after 12 wk of weight lifting training. Dynamic elbow flexion training of one arm resulted in a significant 48% mean increase in the maximal load that could be lifted once (1 RM) and a smaller improvement in isokinetic torque (8.8%) but no change in isometric strength. In the contralateral control arm, 1 RM and isokinetic torque increased by 12.7 and 6.5%, respectively, but isometric strength did not change. The interpolated twitch technique confirmed complete motor unit activation during a maximal isometric contraction of the elbow flexors before and after the training. Bilateral leg press training effected mean increases of 17 and 23% in isokinetic torque and dynamic lifting capacity, respectively. The mean maximal cross-sectional area of the elbow flexors (biceps brachii and brachialis) increased by 17.4% in the trained arm but did not change the control arm. The increase in the mean area of type II fibers in the biceps brachii muscle in the trained arm (30.2%) was greater than the corresponding change in the control arm (10.7%, P less than 0.05). The most significant change in the evoked contractile properties of the trained elbow flexors was the increase in twitch half relaxation time. It is concluded that older individuals retain the potential for significant increases in strength performance and upper limb muscle hypertrophy in response to overload training. PMID- 2272966 TI - Intrapulmonary distribution of bronchial blood flow after moderate smoke inhalation. AB - The systemic blood flow to the airways of the left lung was determined by the radioactive microsphere technique before and 17 h after smoke inhalation in six conscious sheep (smoke group) and six sheep insufflated with air alone (sham group). Smoke inhalation caused a sixfold increase in systemic blood flow to the lower trachea (baseline 10.6 +/- 1.7 vs. injury 60.9 +/- 16.1 ml.min-1.100 g-1) and an 11- to 14-fold increase to the intrapulmonary central airways (baseline range 9.5 +/- 1.9 to 13.5 +/- 3.7 ml.min-1.100 g-1 vs. injury 104.6 +/- 32.2 to 187.3 +/- 83.6 ml.min-1.100 g-1). There was a trend for this hyperemic response to be greater as airway diameter decreased from the trachea to 2-mm-diam central airways. In airways smaller than 2 mm, the hyperemic response appeared to diminish. The total systemic blood flow to whole lung is predominantly to small peripheral airways and showed no significant increase from its baseline level of 17.5 +/- 3.7 ml.min-1.100 g-1 in the lung homogenate. Occlusion of the bronchoesophageal artery decreased central airway blood flow 60-80% and peripheral airway blood flow 40-60% in both the sham and the smoke groups. PMID- 2272968 TI - Flow-volume characteristics in the pulmonary circulation. AB - Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2272967 TI - Temperature dependence of rat diaphragm muscle contractility and fatigue. AB - The diaphragm is a skeletal muscle of mixed fiber type that is unique in its requirement to maintain contractile function and fatigue resistance across a wide range of temperatures to sustain alveolar ventilation under conditions of hypo- or hyperthermia. The direct effect of temperature (15-41 degrees C) on rat diaphragm isometric contractility and fatigue was determined in vitro. As temperature decreased from 37 to 15 degrees C, contraction and relaxation times increased, and there was a left shift of the diaphragm's force-frequency curve, with decreased contractility at 41 and 15 degrees C. Fatigue was induced by 10 min of stimulation with 30 trains/min of 5 Hz at a train duration of 900 ms. Compared with 37 degrees C, fatigue resistance was enhanced at 25 degrees C, but no difference in fatigue indexes was evident at extreme hypothermia (15 degrees C) or hyperthermia (41 degrees C). Only when the fatigue program was adjusted to account for hypothermia-induced increases in tension-time indexes was fatigue resistance evident at 15 degrees C. These findings indicate that despite the diaphragm's unique location as a core structure, necessitating exposure to in vivo temperatures higher than found in limb muscle, the temperature dependence of rat diaphragm muscle contractility and fatigue is similar to that reported for limb muscle of mixed fiber type. PMID- 2272969 TI - Regional H2O2 concentration in rat brain after hyperoxic convulsions. AB - O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3 amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity. PMID- 2272970 TI - Retention of leukocytes in capillaries: role of cell size and deformability. AB - Leukocytes within the circulation are in dynamic equilibrium with a marginated pool, thought to reside mainly within the pulmonary capillaries. The size discrepancy between the mean diameter of circulating leukocytes (6-8 microns) and that of the pulmonary capillaries (approximately 5.5 microns) forces the cells to deform in order to transit the capillary bed. Consequently, we investigated the hypothesis that the biophysical properties of cell size and deformability determined differential leukocyte retention in the lung. Comparison of the filtration properties of human neutrophils, lymphocytes, monocytes, platelets, and erythrocytes through polycarbonate filters (5-micron pore diameter) revealed that the largest leukocytes (neutrophils and monocytes) were retained to the greatest extent and the smaller cells (lymphocytes and platelets) the least. Undifferentiated HL-60 cells, of greater diameter than their differentiated counterparts, were also retained to a greater extent, confirming that cell size was one important determinant of retention in these model capillaries. However, compared with neutrophils, which are of similar diameter, monocytes were retained to a greater extent, suggesting that monocytes might be less deformable than neutrophils. To test this hypothesis, deformability was measured directly using the cell poker. Monocytes were found to be the stiffest, neutrophils the softest, and lymphocytes intermediate. Glutaraldehyde treatment of neutrophils markedly increased their stiffness and decreased their ability to transit the pores of the filters in vitro and the pulmonary microvasculature of rabbits without changing their adhesive properties or size. These observations support the hypothesis that biophysical properties of leukocytes (size and deformability) determine in part their ability to transit the pulmonary capillaries and may determine the magnitude of their marginated pools. PMID- 2272971 TI - Lung mechanics and airway reactivity in sheep during development of oxygen toxicity. AB - The causes of respiratory distress in O2 toxicity are not well understood. The purpose of this study was to better define the airway abnormalities caused by breathing 100% O2. Sheep were instrumented for measurements of dynamic compliance (Cdyn), functional residual capacity by body plethysmography (FRC), hemodynamics, and lung lymph flow. Each day Cdyn and FRC were measured before, during, and after the application of 45 min continuous positive airway pressure (CPAP) at 15 cmH2O. The amount of aerosol histamine necessary to reduce Cdyn 35% from baseline (ED35) was measured each day as was the response to aerosol metaproterenol. Cdyn decreased progressively from 0.083 +/- 0.005 (SE) 1/cmH2O at baseline to 0.032 +/ 0.004 l/cm H2O at 96 h of O2. Surprisingly, FRC did not decrease (1,397 +/- 153 ml at baseline vs. 1,523 +/- 139 ml at 96 h). The ED35 to histamine did not vary among days or from air controls. Metaproterenol produced a variable inconsistent increase in Cdyn. We also measured changes in Cdyn during changes in respiratory rate and static pressure-volume relationships in five other sheep. We found a small but significant frequency dependence of compliance and an increase in lung stiffness with O2 toxicity. We conclude that in adult sheep O2 toxicity reduces Cdyn but does not increase airway reactivity. The large reduction in Cdyn in O2 toxicity results from processes other than increased airway reactivity or reduced lung volume, and Cdyn decreases before the development of lung edema. PMID- 2272972 TI - Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide. AB - SO2 is an environmental pollutant known to elicit bronchospasm in susceptible subjects. We observed that brief exposure of artificially bronchoconstricted cats to high concentrations of SO2 induces a bronchodilator response. This study assessed the characteristics of this response and examined various mechanisms that might underlie it. Cats were anesthetized with diallylbarbital-urethan, and airway smooth muscle tone, measured by lung resistance and dynamic lung compliance, was elevated with a continuous infusion of 5-hydroxytryptamine. Administration of 10 breaths of SO2 via a tracheostomy induced concentration dependent bronchodilation in the range 100-1,000 parts/million. Only infrequently was bronchoconstriction observed before bronchodilation. SO2-induced bronchodilator responses were unaffected by pretreatment with intravenous atropine or propranolol, establishing them as nonadrenergic noncholinergic (NANC) in origin. Neither the ganglionic blocking agent hexamethonium nor the nerve toxin tetrodotoxin influenced the SO2-induced bronchodilation, thus excluding a role for central or local autonomic reflexes in the response. Efforts to modulate the response by pretreatment with the cyclooxygenase inhibitor indomethacin or the mediator release inhibitor cromolyn sodium also were unsuccessful. Administration of acidic aerosols failed to mimic the SO2-induced bronchodilator response. Although the mechanism whereby SO2 induces bronchodilation under these experimental conditions remains unclear, release of a NANC inhibitory transmitter from a neural, epithelial, or other cellular source via a mechanism insensitive to both tetrodotoxin and cromolyn is a distinct possibility. An intrinsic NANC inhibitory system may exist in feline airways functioning as a local regulator of bronchomotor tone and possibly serving to override responses to strong, potentially asphyxial bronchoconstrictive stimuli. PMID- 2272973 TI - High-intensity endurance training in 20- to 30- and 60- to 70-yr-old healthy men. AB - Factors contributing to maximal incremental and short-term exercise capacity were measured before and after 12 wk of high-intensity endurance training in 12 old (60-70 yr) and 10 young (20-30 yr) sedentary healthy males. Peak O2 uptake in incremental cycle ergometer exercise increased from 1.60 +/- 0.073 to 2.21 +/- 0.073 (SE) l/min (38% increase) in the old subjects and from 2.54 +/- 0.141 to 3.26 +/- 0.181 l/min (29%) in the young subjects. Peak cardiac output, estimated by extrapolation from a series of submaximal measurements by the CO2 rebreathing method, increased by 30% (from 12.7 to 16.5 l/min) in the old subjects, associated with a 6% increase (from 126 to 135 ml/l) in arteriovenous O2 difference; in the young subjects there were equal 14% increases in both variables (18.0 to 20.5 l/min and 140 to 159 ml/l, respectively). Submaximal mean arterial pressure and cardiac output were lower posttraining in the old subjects; total vascular conductance and cardiac stroke volume increased. Although peak power at the start of a short-term maximal isokinetic test did not change, total work accomplished in 30 s at a pedaling frequency of 110 revolutions/min increased in both groups, from 11.2 to 12.6 kJ and from 15.7 to 16.9 kJ in the old and young, respectively; fatigue during the 30-s test was less, and postexercise plasma lactate concentrations were lower. In older subjects, increases in aerobic power after high-intensity endurance training are at least as large as in younger subjects and are associated with increases in vascular conductance, maximal cardiac output, and stroke volume. PMID- 2272974 TI - Exercise training enhances leg vasodilatory capacity of 65-yr-old men and women. AB - To determine whether extremity vasodilatory capacity may be augmented in older persons by endurance exercise training, lower leg blood flow and conductance were characterized plethysmographically at rest and during maximal hyperemia in 9 men and 10 women aged 64 +/- 3 (SD) yr before and after 31 +/- 6 wk of walking and jogging at 70-90% of maximal oxygen uptake for 45 min 3-5 days/wk. Maximal oxygen uptake expressed as milliliters per kilogram per minute improved 25% in men and 21% in women (P less than 0.01). Maximal leg blood flow and conductance increased in all nine men by an average of 39 +/- 33 (P less than 0.001) and 42 +/- 44% (P less than 0.004), respectively. Results were more variable in women and achieved unequivocal statistical significance only for maximal blood flow (+33 +/- 54% for blood flow and +29 +/- 55% for conductance; P less than 0.02 and P = 0.05, respectively). Body weight and skinfold adiposity declined in both sexes (P less than 0.05). Enhancement of vasodilatory capacity was related to weight loss in men and adipose tissue loss in women (r = 0.61 and 0.51, respectively; P less than 0.05). There were no significant changes in exercise capacity, body weight, or maximal blood flow in four male and three female controls aged 66 +/- 4 yr. Thus adaptability of the lower limb circulation to endurance exercise training is retained to at least age 65 yr. PMID- 2272975 TI - Myoelectric manifestations of fatigue in voluntary and electrically elicited contractions. AB - The time course of muscle fiber conduction velocity and surface myoelectric signal spectral (mean and median frequency of the power spectrum) and amplitude (average rectified and root-mean-square value) parameters was studied in 20 experiments on the tibialis anterior muscle of 10 healthy human subjects during sustained isometric voluntary or electrically elicited contractions. Voluntary contractions at 20% maximal voluntary contraction (MVC) and at 80% MVC with duration of 20 s were performed at the beginning of each experiment. Tetanic electrical stimulation was then applied to the main muscle motor point for 20 s with surface electrodes at five stimulation frequencies (20, 25, 30, 35, and 40 Hz). All subjects showed myoelectric manifestations of muscle fatigue consisting of negative trends of spectral variables and conduction velocity and positive trends of amplitude variables. The main findings of this work are 1) myoelectric signal variables obtained from electrically elicited contractions show fluctuations smaller than those observed in voluntary contractions, 2) spectral variables are more sensitive to fatigue than conduction velocity and the average rectified value is more sensitive to fatigue than the root-mean-square value, 3) conduction velocity is not the only physiological factor affecting spectral variables, and 4) contractions elicited at supramaximal stimulation and frequencies greater than 30 Hz demonstrate myoelectric manifestations of muscle fatigue greater than those observed at 80% MVC sustained for the same time. PMID- 2272976 TI - Selective pulmonary vasodilation with ATP-MgCl2 during pulmonary hypertension in lambs. AB - We investigated the effects of infusions of ATP-MgCl2 on the circulation in 11 spontaneously breathing newborn lambs during pulmonary hypertension induced either by the infusion of U-46619, a thromboxane A2 mimetic, or by hypoxia. During pulmonary hypertension induced by U-46619, ATP-MgCl2 (0.01-1.0 mg.kg-1.min 1) caused a significant dose-dependent decrease in pulmonary arterial pressure (12.4-40.7%, P less than 0.05), while systemic arterial pressure decreased only at the highest doses (P less than 0.05). Left atrial infusions of ATP-MgCl2 caused systemic hypotension without decreasing pulmonary arterial pressure. During hypoxia-induced pulmonary hypertension, ATP-MgCl2 caused a similar significant dose-dependent decrease in pulmonary arterial pressure (12.0-41.1%, P less than 0.05), while systemic arterial pressure decreased only at high doses (P less than 0.05). Regression analysis showed selectivity of the vasodilating effects of ATP-MgCl2 for the pulmonary circulation during pulmonary hypertension induced either by U-46619 or hypoxia. ATP-MgCl2 is a potent vasodilator with a rapid metabolism that allows for selective vasodilation of the vascular bed first encountered (pulmonary or systemic). We conclude that infusions of ATP-MgCl2 may be clinically useful in the treatment of children with pulmonary hypertension. PMID- 2272977 TI - Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. AB - In a variety of lung diseases the respiratory epithelial surface must contend with an increased burden of neutrophil elastase (NE). One candidate for augmenting epithelial anti-NE protection is the secretory leukoprotease inhibitor (SLPI). In vitro evaluation demonstrated that 96 +/- 1% of the recombinant SLPI (rSLPI) molecules were capable of inhibiting NE, with an association rate constant of 7.1 +/- 0.1 X 10(6) M-1.s-1. Evaluation of rSLPI after in vitro and in vivo aerosolization showed that aerosolization did not alter rSLPI. Aerosolization of a single dose of 50 mg rSLPI to sheep resulted in a fourfold increase of the anti-NE capacity in epithelial lining fluid (ELF) at 3 h, with a half-life in ELF of 12 h. After aerosolization some rSLPI appeared in lung lymph. Simultaneous aerosolization of rSLPI and recombinant alpha 1-antitrypsin (rAAT) demonstrated a molar ratio of the concentration in lymph to the concentration in ELF 3 h after the aerosol eightfold higher for rAAT than for rSLPI. Overall, these observations demonstrate that it is feasible to use aerosolized rSLPI to directly augment the anti-NE capacity of the lung, particularly on the pulmonary epithelial surface. PMID- 2272978 TI - Effects of a 36-hour fast on human endurance and substrate utilization. AB - To determine if prolonged fasting affects substrate utilization and endurance time, seven trained men exercised to exhaustion on a cycle ergometer at 50% maximum oxygen consumption (VO2max) in an overnight-fasted [postabsorptive (PA)] state and after a 36-h fast (F). Fasting produced significant elevations in the resting concentrations of blood free fatty acids (FFA; 1.16 +/- 0.05 vs. 0.56 +/- 0.06 mM, F vs. PA, respectively, a 107% increase), beta-hydroxybutyrate (beta-OH, 2.06 +/- 0.66 vs. 0.15 +/- 0.06 mM, a 1,270% increase), and glycerol (0.12 +/- 0.03 vs. 0.04 +/- 0.01 mM, a 200% increase), with a significant decline in glucose (79.79 +/- 2.12 vs. 98.88 +/- 3.11 mg/dl, a 19% decrease). Exercise in the F trial increased FFA, decreased glucose, and significantly elevated beta-OH and glycerol over the PA trial. There was no difference in blood glucose concentration between trials at exhaustion. However, F produced a significant decrement in exercise endurance time compared with the PA trial (88.9 +/- 18.3 vs. 144.4 +/- 22.6 min, F vs. PA, a 38% decrease). Based on the respiratory exchange ratio, fasting led to a greater utilization of lipids during rest and exercise. It was concluded that 1) a 36-h fast significantly altered substrate utilization at rest and throughout exercise to exhaustion, 2) glucose levels do not appear to be the single determinant of time to exhaustion in submaximal exercise, and 3) despite the apparent sparing of carbohydrate utilization with the 36-h fast, endurance performance was significantly decreased. PMID- 2272979 TI - Intrapulmonary catabolism of surfactant-saturated phosphatidylcholine in rabbits. AB - Intrapulmonary surfactant catabolism was investigated by use of a phospholipase A1- and A2-resistant analogue of dipalmitoylphosphatidylcholine (DPC), 1,2 dipalmitoyl-sn-glycero-3-phosphocholine (DPC ether). [14C]DPC ether, made into liposomes with [3H]DPC and associated with 32P-labeled rabbit surfactant, was given intratracheally to 1-kg rabbits, which were killed at preset times to 48 h. Recoveries of radiolabel as saturated phosphatidylcholine (Sat PC) isolated from alveolar wash (AW), postlavage lung homogenate (LH), and alveolar macrophages were measured. All groups had similar AW and LH Sat PC pool sizes, indicating no perturbation of endogenous Sat PC pools. Despite a nearly fivefold accumulation of [14C]DPC ether in the lung by 48 h (P less than 0.01), the three probes had similar alveolar clearance curves. Furthermore, the Sat PC reutilization efficiency (41.6%) and turnover time (5.9 h) calculated for DPC ether were not different from values for the DPC and rabbit surfactant. Of the DPC ether (0.7%) and DPC (9%) labels recovered as PC in organs outside the lung, greater than 85% was unsaturated, indicating de novo synthesis using precursors from degraded PC. DPC ether was a useful probe of intrapulmonary DPC catabolism, and after alveolar uptake there was no direct reentry of intact DPC from the catabolic compartment(s) into the secretory pathway. PMID- 2272980 TI - Atelectasis affects the rate of arterial desaturation during obstructive apnea. AB - Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed. PMID- 2272981 TI - Influence of vascular distending pressure on regional flows in isolated perfused dog lungs. AB - To confirm the regional differences in vascular pressure vs. flow properties of lung regions that have been documented in zone 2 conditions [pulmonary venous pressure (Ppv) less than alveolar pressure], regional distending pressure vs. flow curves in zone 3 were generated by use of isolated blood-perfused dog lungs (3 right and 5 left lungs). Each lung was kept inflated at constant inflation pressure (approximately 50% of full inflation volume) while radioactively labeled microspheres were injected at different settings of Ppv. To achieve maximal vascular distension, Ppv was increased to approximately 30 cmH2O above alveolar pressure for the first injection. Subsequent injections were made at successively lower Ppv's. The difference between pulmonary arterial pressure and Ppv was kept constant for all injections. As was found in zone 2 conditions, there were differences in the regional distending pressure vs. flow curves among lung regions. To document the regional variability in the curves, the distribution of flow at a regional Ppv of 30 cmH2O above alveolar pressure was analyzed. There was a statistically significant linear gradient in this flow distribution from dorsal to ventral regions of the lungs but no consistent gradient in the caudad to cephalad direction. These results indicate that, even in near-maximally distended vessels, the dorsal regions of isolated perfused dog lungs have lower intrinsic vascular resistance compared with ventral regions. PMID- 2272982 TI - Sustainable inspiratory pressures over varying flows, volumes, and duty cycles. AB - This study identifies the influence of flow (0.5-2.0 l/s), duty cycle (0.29 0.57), and tidal volume (1.08-2.16 liters) on sustainable inspiratory muscle pressure (Pmus) and transdiaphragmatic pressure (Pdi) development. Six normal humans performed endurance tests using an isoflow method, which allowed for measurements of maximum dynamic Pmus and Pdi, with controlled lung inflation. The subjects repeated maximum dynamic voluntary inspirations for 10 min. Pressures dropped exponentially from initial measurements at rest (Pmusi or Pdi) to sustainable values (Pmus or Pdis). As flow and tidal volume increased, maximum initial and sustainable pressures decreased significantly. However, at a constant duty cycle, the sustainable dynamic pressures remained predictable fractions of initial dynamic pressures (i.e., Pmuss/Pmusi or Pdis/Pdii), regardless of changes in flow and tidal volume. In contrast, as duty cycle increased, the sustainable fractions significantly decreased for both Pdi and Pmus. For example, at a duty cycle of 0.29, Pmuss/Pmusi was approximately 0.71, and at a duty cycle of 0.57, Pmuss/Pmusi was approximately 0.62. Calculated sustainable pressure-time indexes varied significantly between 0.16 to 0.32 for Pmus and 0.11 to 0.22 for Pdi over the breathing patterns studied. We conclude that 1) the maximum dynamic pressure that can be sustained at a given duty cycle is a predictable fraction of the maximum dynamic pressure that can be generated at rest when measured under the same conditions of inspiration and 2) the sustainable fraction of initial dynamic pressure significantly decreases with increasing duty cycle. PMID- 2272983 TI - Failure of therapy with 2,3-dihydroxybenzoic acid to modify the course of sepsis induced lung injury. AB - Oxidant-induced injury of the pulmonary microvasculature reportedly contributes to an increase in microvascular permeability and pulmonary hypertension, both of which are principal features of acute lung injury (ALI). We tested the hypothesis that antioxidant therapy with 2,3-dihydroxybenzoic acid (DHB), initiated in awake sheep after the development of sepsis-induced ALI, would ameliorate the progression of these lesions. DHB has many actions that suggested to us the potential for demonstrating benefit in ALI complicating sepsis; it is a nontoxic hydroxyl-radical scavenger that also inhibits the cyclooxygenase pathway and acts as a weak iron chelator. In preliminary experiments, we demonstrated that pretreatment with DHB prevented an increase in mean pulmonary arterial pressure, plasma thromboxane A2, measured as its metabolite thromboxane B2, and lymph total protein clearance that otherwise followed an infusion of zymosan-activated plasma (ZAP) in sheep. In subsequent experiments, 12 additional sheep were rendered septic by cecal ligation and perforation. Twenty-four to 36 h after cecal ligation and perforation, an increase in lung microvascular permeability was confirmed, because pulmonary lymph flow had increased by 82% while the mean lymph to-plasma total protein ratio was unchanged from baseline. At this point, six sheep were then treated with parenteral DHB and six with DHB vehicle for the subsequent 24 h. In contrast to the demonstrated benefit of DHB pretreatment in preventing ALI secondary to an infusion of ZAP, the progressive increase in lymph total protein clearance that complicated septic lung injury in the DHB vehicle group throughout this 24-h study period was not ameliorated in the DHB treatment group. However, DHB did prevent a modest increase in mean pulmonary arterial pressures that was demonstrated in the DHB vehicle group throughout this 24-h treatment period. Although pretreatment prevented ALI after a ZAP infusion, we conclude that DHB only incompletely modified disease progression when administered after the onset of sepsis-induced ALI because it ameliorated the pulmonary hypertensive response without concurrently modifying an increase in lung microvascular fluid flux. PMID- 2272984 TI - Immunomodulations induced in rats by exercise on a treadmill. AB - Various regimens of treadmill exercise (0% slope) were used with rats: 60 min at 15 m/min (T-15), 180 min at 10 m/min (T-10), and 60 min/day at 15 m/min for 6 consecutive days (T-15-6). Exercise resulted in 1) decreases in the absolute number of mononuclear spleen cells in T-10 rats, 2) significant increases in in vitro splenic T-cell blastogenesis in response to phytohemagglutinin in T-10 rats, and 3) significant decreases in T-cell blastogenesis in T-15-6 rats. T-15-6 rats were given aminoglutethimide per os before exercise sessions to study the role of corticosteroids in the alteration of splenic T-cell blastogenesis. Aminoglutethimide significantly increased the T-cell blastogenesis in these T-15 6 rats compared with those not given aminoglutethimide, whereas it had no effect on immune parameters of sedentary rats. These results show that immunomodulations in the rat depend on the treadmill exercise regimen employed. If the mechanisms of the immunomodulation induced by isolated exercise of long duration are not elucidated, these data suggest that corticosteroids are involved in the alteration in T-cell blastogenesis induced by chronic muscular exercise. PMID- 2272985 TI - Residues in foods. 1989. AB - A total of 18,798 samples of domestically produced food from all 50 states and Puerto Rico and imported food from 88 countries were analyzed for pesticide residues in 1989. Of these, 18,113 were surveillance samples, which are collected when there is no suspicion of a pesticide problem. No residues were found in 65% of domestic surveillance samples and in 67% of import surveillance samples. Less than 1% of the 18,113 surveillance samples contained residues that exceeded EPA tolerances. Findings in the 685 compliance samples reflect the fact that they are collected and analyzed when a pesticide problem is suspected. The 1989 Total Diet Study findings show that intakes of pesticide residues are generally well below standards set by FAO/WHO as well as by EPA. Results for 1989 are similar to those for 1987 and 1988 and continue to demonstrate that the levels of pesticide residues in the U.S. food supply are low. PMID- 2272987 TI - Total diet study. Section A: strontium-90 and cesium-137 content. 1963. PMID- 2272986 TI - Total diet study. 1963. PMID- 2272989 TI - Total diet study. Section C: pesticide residue content. 1963. PMID- 2272988 TI - Total diet study. Section B: nutrient content. 1963. PMID- 2272991 TI - Liquid chromatographic determination of pentaerythritol tetranitrate in pharmaceuticals: collaborative study. AB - A liquid chromatographic (LC) method for the determination of pentaerythritol tetranitrate (PETN) in pharmaceutical formulations and the bulk drug triturate was evaluated in an interlaboratory study that included 12 participating laboratories. The procedure involves extraction of the active ingredient with mobile phase, followed by filtration of the extract and reverse-phase liquid chromatography using an octadecylsiliane bonded phase column and UV detection at 230 nm. The mobile phase composition is 35% water in acetonitrile (v/v). Three bulk drug samples (20, 20, and 35% PETN), 2 commercial tablet formulations (20 and 80 mg PETN/tablet), and 1 commercial capsule formulation (45 mg PETN/capsule) were analyzed in duplicate by the proposed method. Repeatability (sr, RSDr) and reproducibility (SR, RSDR) based on peak height measurement for these samples ranged from 0.0066 to 0.1806 (0.53-3.36%) and 0.0165 to 0.2075 (0.76-3.86%), respectively. Results for peak area measurements ranged from 0.0145 to 0.2011 (0.93-3.74%) and 0.0231 to 0.2091 (1.28-3.89%), respectively. The method has been approved interim official first action by AOAC. PMID- 2272990 TI - Precision parameters of methods of analysis required for nutrition labeling. Part I. Major nutrients. AB - Major components of foods and feeds are fat, protein, and carbohydrates. Fat and protein are determined by direct measurements that are interpreted as the quantity of the constituent. Carbohydrates are usually calculated by difference. For this calculation, values for moisture/solids, ash, and "fiber" are also needed. The readily available collaborative studies for the determination of these major components are reviewed in an attempt to assign precision parameters to validated methods of analysis. When a number of studies for the same analyte, in the same food, by the same method are available, it is seen that the precision parameters among laboratories (standard deviations, SR; relative standard deviations, RSDR) and the ISO maximum tolerable difference functions (repeatability value, r; reproducibility value, R) are not characterized by any conventional distribution. The precision data are best summarized as a median or average parameter and the interval containing the centermost 90% of reported values. Typically, the precision of methods of analysis can be expressed as a function of concentration only, independent of analyte, matrix, and method. The average RSDR value from each collaborative data set can then be used as the numerator in a ratio containing, as the denominator, the value calculated from the Horwitz equation: RSDR = 2 exp (1 - 0.5 log C) where C is the concentration as a decimal fraction. A series of ratios consistently above 1, and especially above 2, probably indicates that a method is unacceptable with respect to precision. By this criterion, only the protein (Kjeldahl) determination is unqualifiedly acceptable with a 90% interval for RSDR of 1 to 3% at C values above about 0.01 (1 g/100 g). Fat, moisture/solids, and ash are acceptable down to limiting concentrations in the region of 1 to 5 g/100 g, if a test portion large enough to provide at least 50 mg of weighable residue or volatiles is specified. Measurements of individual carbohydrates and fiber-related analytes have unexpectedly poor precisions among laboratories. The variability, although high, may still be suitable for nutrition labeling. Reliability of analyses for the control of labeling of the primary nutrients must be achieved through quality assurance programs that require strict adherence to the directions of empirical methods and the use of suitable reference materials for absolute methods. PMID- 2272992 TI - Determination of diclofenac sodium and related compounds in raw materials and formulations. AB - A liquid chromatographic method has been developed for determination of drug and related compounds in diclofenac sodium raw material, slow-release, and enteric coated tablets. The method specifies a 5 microns octadecylsilane bonded phase column, a mobile phase of tetrahydrofuran-acetonitrile-buffer, pH 5 (1 + 4 + 8.3), and detection at 229 nm. The method resolves 10 known related compounds with limits of quantitation of 0.2% or less. Seventeen drug raw material samples were evaluated. Total impurity levels ranged from 0.1 to 0.9%. The method has also been used for determination of drug content in raw materials and formulations. Mean assay levels in drug raw materials ranged between 98.3% and 101.8%. PMID- 2272993 TI - Gas chromatographic determination of incurred dimetridazole residues in swine tissues. AB - A gas chromatographic method for determination of 2-hydroxymethyl-1-methyl-5 nitroimidazole (DMZOH), the hydroxy metabolite of dimetridazole, in swime muscle has been developed. The method uses cleanup steps similar to those of an earlier polarographic method. The present method is capable of quantitating levels as low as 2 ppb and detecting less than 1 ppb. Recoveries from 30 control tissues spiked at 1, 2, or 4 ppb averaged 80.4%. Performance of the method in incurred tissue was documented and limited data on the depletion of the metabolite in muscle were generated. The muscle of swine given 150 ppm dimetridazole in feed for 14 days contained less than 1 ppb DMZOH at 12 h withdrawal time. PMID- 2272994 TI - Rapid method for determination of leucogentian violet in chicken fat by liquid chromatography with electrochemical detection. AB - The metabolite leucogentian violet (LGV) was found in chicken fat obtained from chickens dosed with gentian violet (GV); however, no residues of the parent compound, GV, and its oxidized metabolites were found. Therefore, a rapid method was developed for the specific determination of LGV in chicken fat. Chicken fat containing LGV is separated from the cellular protein with methylene chloride. LGV is then separated from the fat by partition extraction with an aqueous acid phase in which LGV is protonated, and the fat is discarded with the methylene chloride layer. The aqueous solution is neutralized, LGV is re-extracted into methylene chloride, and the methylene chloride is evaporated. An acetonitrile water solution containing LGV is filtered before liquid chromatography using a cyano column, an acetate buffer-acetonitrile mobile phase, and an electrochemical detector set at a potential of +1.000 V. Average recoveries of LGV from chicken fat were 83.9% with a coefficient of variation (CV) of 12.9% for the 5 ppb level; 82.8% with a CV of 13.5% for the 10 ppb level; and 77.7% with a CV of 2.56% for the 20 ppb level. Levels of incurred LGV in chicken fat averaged 49.3 ppb with a CV of 2.43%. PMID- 2272995 TI - Atomic absorption spectrophotometric method for determination of polydimethylsiloxane residues in pineapple juice: collaborative study. AB - An atomic absorption spectrophotometric method for determination of polydimethylsiloxane (PDMS) residues in pineapple juice was collaboratively studied by 9 laboratories. PDMS residues are extracted from pineapple juice with 4-methyl-2-pentanone and the extracted silicone is measured by atomic absorption spectrophotometry using a nitrous oxide/acetylene flame. Collaborators analyzed 5 samples including 1 blind duplicate. Reproducibility relative standard deviations (RSDR) were 13.1% at 31 ppm, 6.9% at 18 ppm, 14.8% at 7.9 ppm, and 16.1% at 4.9 ppm PDMS. The method has been approved interim official first action by AOAC. PMID- 2272996 TI - Gram-negative identification card for identification of Salmonella, Escherichia coli, and other Enterobacteriaceae isolated from foods: collaborative study. AB - Twelve laboratories evaluated the Gram-Negative Identification (GNI) Card to identify members of the Enterobacteriaceae. Eighty-four isolates, previously isolated from foods, were used in the collaborative study; the isolates represented 12 genera within the Enterobacteriaceae group. Each collaborator streaked each isolate on tryptic soy agar plates for purity. In the method, plates are incubated 18-24 h at 35 degrees C. Isolated colonies are then subcultured to tryptic soy agar slants and incubated 18-24 h at 35 degrees C. An emulsion is made from the growth on the slant in 1.8 mL 0.45% sodium chloride solution. The GNI Card is filled and placed in a reader/incubator. Isolates are identified and an identification is printed. The Vitek System correctly identified 96.7% of Salmonella sp., 97.0% of Escherichia coli, and an average of 93.8% of the other enteric genera. The method using the Vitek System and GNI Card has been approved interim official first action by AOAC as a screening method for the presumptive identification of Salmonella sp., E. coli, and other Enterobacteriaceae isolated from foods. PMID- 2272997 TI - Improved hydrophobic grid membrane filter method, using EF-18 agar, for detection of Salmonella in foods: collaborative study. AB - A collaborative study was carried out in 30 laboratories to validate improvements to the official final action hydrophobic grid membrane filter (HGMF) screening method for Salmonella in foods, 985.42, by comparing the performance of the improved HGMF method against that of the AOAC/BAM conventional culture method. Six products were included in the collaborative study: milk chocolate, raw deboned poultry meat, black pepper, soy flour, egg yolk powder, and nonfat dry milk. The raw deboned poultry meat was naturally contaminated with Salmonella, and the remaining 5 products were each inoculated in advance with low levels of individual Salmonella serotypes. The AOAC/BAM method produced 11 false negative results and the improved HGMF method produced 18 false negative results. The improved HGMF Salmonella method has been approved interim official first action for all foods to replace the HGMF official final action method, 985.42. PMID- 2272998 TI - Gas chromatographic method for determination of p,p'-DDT in DDT technical and formulated products: collaborative study. AB - A gas chromatographic (GC) method for determination of p,p'-DDT in technical and formulated products was developed and it performed well in an initial small collaborative study among 4 laboratories. Samples are dissolved in chloroform, and p,p'-DDT is separated on an OV-210 column and determined by GC analysis with flame ionization detection. 2,2'-Dinitrobiphenyl is used as an internal standard. The method was subjected to an international collaborative study with 10 participating laboratories. Collaborators received matched pairs of technical DDT products and of water-dispersible powder, emulsifiable concentrate, and dustable powder formulations. Relative standard deviations for reproducibility (RSDR) for the paired samples were 1.16, 1.48, 2.08, and 1.80%, respectively. The method has been approved interim official first action by AOAC as a CIPAC-AOAC method. PMID- 2272999 TI - Levels of 3,3',4,4'-tetrachloroazobenzene in diuron and linuron herbicide formulations. AB - Levels of 3,3',4,4'-tetrachloroazobenzene (TCAB) were determined by capillary gas chromatography (GC) with electron-capture detection (ECD) in 25 samples of diuron and linuron formulations obtained from the Canadian market. Acidic aqueous methanol was used to retain urea herbicide and the neutral TCAB was allowed to partition into hexane. Silica gel was used for cleanup of the hexane extract, followed by GC/ECD determination. Recovery data obtained at 4 different spiking levels (i.e., 0.3, 0.1, 1.0, and 5.0 ppm) in linuron averaged 93, 86, 85, and 97%, respectively. For diuron, spiking was done at 0.5, 1.0, and 5.0 ppm levels and the corresponding average percent recoveries were 95, 101, and 104. The TCAB contamination level observed in diuron on a 100% active ingredient basis ranged from 0.15 to 3.38 ppm, whereas in linuron, it varied from 0.91 to 10.28 ppm. PMID- 2273001 TI - Gas chromatographic determination of systemic fungicide tricyclazole in soil and water. AB - A method is described for determination of tricyclazole residues in soil and water. Tricyclazole is extracted from soil by refluxing with ethyl acetate acetone (80 + 20 v/v) and from water by partitioning into dichloromethane. The soil extract is purified by coagulation. The compound is detected and measured by gas chromatography using a flame photometer operated in the sulfur mode. Detection limits are 8 ppb for soil and 0.8 ppb for water. Recoveries for control samples fortified with tricyclazole at 0.1-5.0 ppm averaged 97.1% for soil and 108.1% for water. PMID- 2273000 TI - Ion-pairing liquid chromatographic determination of benzimidazole fungicides in foods. AB - A method is described for determining residues in foods of thiabendazole, thiophanate methyl, the di-oxygen analogue metabolite [dimethyl 4,4'-O-phenylene bis (allophanate)] that is the metabolite name of the latter, and methyl-2 benzimidazole carbamate, which is the major metabolite and fungitoxic principle common to both thiophanate methyl and benomyl. The residues are extracted from the product using methanol and are partitioned into dichloromethane after initial acidification and again after subsequent alkalinization of the extract. Residues are separated and quantified by reverse-phase liquid chromatography using an ion pairing mobile phase with UV and fluorescence detectors in tandem. Recoveries from 7 different food crops fortified at 0.2-35 ppm levels ranged from 64 to 105%. PMID- 2273002 TI - Mineralization procedure for determination of copper in aerosols using photometric method based on copper-BPKQH complex. AB - A mineralization procedure is proposed for copper aerosols in which samples are mineralized by wet-ashing with HNO3 + HCIO4 mixture. Copper content is determined by a photometric method based on formation of a complex between copper and benzyl 2-pyridyl ketone 2-quinolylhydrazone (BPKQH). The influence of pH, ethanol content, and reagent concentration is studied. Copper determination at pH = 7.3, in the range 0.05 to 3 ppm is proposed. Mineralization with HNO3 is carried out in different conditions of evaporation (with or without dryness) and manipulation. Analysis of variance by the (ANOVA) single factor method shows that digestion conditions significantly increase the variability of results. Repeatability assays suggest that nitric acid alone gives low precision. Recovery assays reveal that the HNO3 digestion process causes copper loss by volatilization. Mineralization with HNO3 + HCIO4 is optimized on the basis of the accuracy and precision obtained. The ANOVA method suggests that mineralization conditions significantly increase total variability of results and also that results of the photometric method are not significantly different from those of the AAS method. The optimum mineralization procedure gave an RSD of 0.63% and a copper recovery of 98.4%. The combined digestion and quantification method was applied to determination of copper in aerosol samples obtained during leaf spraying operations of olive trees in the field. PMID- 2273003 TI - Simple analytical method for organophosphorus pesticide residues in milk. AB - A simple method for determination of organophosphorus pesticide residues at the parts per million level in milk was developed. Pesticide residues were extracted with acetonitrile added to aqueous milk, fat was removed by zinc acetate addition and dichloromethane partition, and analytes were concentrated and analyzed by wide-bore capillary column gas chromatography. Recoveries of 6 pesticides spiked in milk samples at levels of 0.1 and 1.0 micrograms/mL were 82.1-93.8% and 79.7 96.6%, respectively. Triplicate samples spiked with 6 pesticides at 1 microgram/mL were analyzed independently by 3 laboratories. Average recoveries were greater than 80%, and the mean coefficients of variation for the complete study were 2.9% for diazinon, 5.4% for dimethoate, 4.6% for malathion, 4.6% for parathion, 4.9% for EPN, and 6.1% for phosalone. PMID- 2273004 TI - Artifact formation during smoke trapping: an improved method for determination of N-nitrosamines in cigarette smoke. AB - Studies in our laboratory revealed artifactual formation of N-nitrosamines during trapping of mainstream and sidestream tobacco smoke by the method of Hoffmann and coworkers (2, 4). Both volatile and tobacco-specific N-nitrosamines were produced. This artifact formation took place on the Cambridge filter, which is part of the collection train used in the previously published procedure. When the filter was treated with ascorbic acid before smoke collection, artifact formation was inhibited. The improved method resulting from these studies was applied to a comparative analysis of N-nitrosamines in smoke from cigarettes that heat, but do not burn, tobacco (the test cigarette) and several reference cigarettes. Concentrations of volatile and tobacco-specific N-nitrosamines in both mainstream and sidestream smoke from the test cigarette were substantially lower than in the reference cigarettes. PMID- 2273005 TI - Gas chromatographic determination of total iodine in foods. AB - A gas chromatographic (GC) method has been developed for determination of total iodine in foods, based on the reaction of iodine with 3-pentanone. Organic matter of a sample is destroyed by an alkaline ashing technique. Iodide in a water extract of the ash residues is oxidized to free iodine by adding dichromate in the presence of sulfuric acid. Liberated iodine is reacted with 3-pentanone to form 2-iodo-3-pentanone, extracted into n-hexane, and then determined by gas chromatography with an electron-capture detector. Recoveries of iodide from spiked food samples ranged from 91.4 to 99.6%. Detection limit for iodine is 0.05 micrograms/g. PMID- 2273006 TI - Fast and simple liquid chromatographic determination of nonphosphorylated thiamine in infant formula, milk, and other foods. AB - A very fast and simple method for determination of nonphosphorylated thiamine in infant formula products, milk, and other nonfortified foods using reverse-phase ion-pairing liquid chromatography (LC) has been developed. Sample preparation consists of merely acid treatment to precipitate protein, followed by gravity filtration. No concentration, extraction, derivatization, or preliminary column cleanup is necessary. The chromatography is done on muBondapack C18 with an aqueous mobile phase containing 0.15% sodium hexane sulfonate, 20% MeOH, 1.5% HOAc, and 0.1% EDTA at a flow rate of 2.5 mL/min. Ultraviolet detection at 248 nm is used. A typical run takes 7 min, and 60 samples can be processed in 4 h. Results average from 96 to 104% of theory for the infant formula products analyzed. A 99 to 103% recovery of spike has been demonstrated. Method precision is good (2 to 4% RSD, short-term, and 2 to 5% RSD, long-term, depending on sample type). Peak separation from thiamine phosphate esters is achieved. Specificity is demonstrated by UV spectral scan and absorbance ratios. Equivalency to a microbial method (validated against the official AOAC fluorometric method) was established. The method is used for high-volume quality control testing of milk based infant formula products in the ready-to-use, concentrate, or powder form. PMID- 2273007 TI - Survey of total and bioavailable chromium in grain and cereal products by atomic absorption spectrophotometry. AB - The chromium content of samples of cereals, legumes, oil seeds, and alimentary pastes (in the latter, bioavailable chromium as well) was determined by atomic absorption spectrophotometry. The chromium content in whole cereals differs substantially and is mostly concentrated in pericarps. Variations occur not only among different types of cereals, but also among cereals of the same type, depending on the areas of origin. Concentration varies substantially even in samples of legumes and oil seeds. The content of bioavailable chromium (ethanol extractable) is, in most cases, more than 50% of the total chromium amount. This makes these products particularly interesting as dietary supplements. PMID- 2273008 TI - In vivo rat assay for true protein digestibility: collaborative study. AB - Eight laboratories participated in a collaborative study to estimate precision of a standardized rat assay for determining true protein digestibility in selected animal, fish, and cereal products. Each of 7 test protein sources (casein, tuna fish, macaroni/cheese, pea protein concentrate, rolled oats, pinto beans, and nonfat dried milk) was fed as the sole source of protein at a 10% protein level in mixed diets. Each diet was fed to 2 replicate groups of 4 rats each for a 4 day acclimation period and a 5-day balance period. Mean digestibilities ranged from 98.6% for casein to 72.6% for pinto beans. Repeatability standard deviations ranged from 0.5 to 2.0%; the mean relative standard deviation for repeatability was 0.9% (range 0.5-2.8%). Reproducibility standard deviations ranged from 1.2 to 3.2%, and the mean relative standard deviation for reproducibility was 2.4% (range 1.3-4.4%). The method has been approved interim official first action for determining true protein digestibility in foods and ingredients. PMID- 2273009 TI - Validation of a method for determination of tetracycline antibiotics in salmon muscle tissue. AB - A method was validated for analysis of oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC) in fortified salmon muscle tissue. Recoveries of OTC were 100 +/- 6, 86 +/- 6, and 82 +/- 5% (n = 6) at fortification levels of 1.0, 0.5, and 0.2 ppm, respectively. Recoveries of TC were 68 +/- 4, 65 +/- 6, and 66 +/- 7%; recoveries of CTC were 45 +/- 9, 48 +/- 8, and 0%, respectively. Detection limits for OTC and TC were 0.08 and 0.09 ppm, respectively. PMID- 2273010 TI - Inpatient psychiatric treatment of children and adolescents: a review of outcome studies. AB - All outcome studies of child and adolescent residential treatment and inpatient psychiatric hospitalization reported in the literature from 1975 to the present were examined. A set of statistical procedures was developed to integrate the findings of the 34 studies, which provided a weighted predictive value for 10 variables. Psychiatric hospitalization was often beneficial, particularly if a specialized treatment program and aftercare were available and if the child presented with a less pathological clinical picture. Age at admission and sex bore no relationship to favorable outcome, and IQ and length of stay yielded only a modest relationship to outcome. Recommendations to guide future researchers are offered that will provide new insights into better understanding inpatient psychiatric treatment. PMID- 2273011 TI - The DSM-III-R field trial of pervasive developmental disorders. AB - This article describes the method and results of a national field trial of the proposed criteria for the DSM-III-R diagnosis of autistic disorder at 11 sites which have experience in diagnosing pervasive developmental disorders. Using the diagnosis of autistic disorder made by expert clinicians as a standard, the diagnostic criteria that were finally included in DSM-III-R demonstrated high sensitivity and specificity across different age groups and in children with and without language. PMID- 2273012 TI - Age of symptom onset in young children with pervasive developmental disorders. AB - Data from 39 young children with autism or other pervasive developmental disorders were examined to determine the relevance of the age of social symptom onset and language symptom onset to other developmental variables. Contrary to the authors' hypotheses, earlier onset of social symptoms was not indicative of a greater severity of autistic symptoms, retardation, or incidence of insecure attachments. Early speech loss was associated with lower IQ, greater social deficits, and poorer language development, while the presence of useful speech at age 2 was related to better functioning in multiple domains. Thus, language functions, rather than the social behaviors examined, carried the greatest predictive power regarding short-term outcomes. PMID- 2273013 TI - Detection of maternal antibodies in infantile autism. AB - Maternal antibodies reactive with antigenic proteins expressed on the cell surface of paternal lymphocytes can be detected in couples with histories of more than one miscarriage or stillbirth. It is possible, but not proven, that these antibodies also react with tissues of the fetus and result in fetal death. Since many mothers of autistic children have a history of pregnancy disorder, antibodies were studied in 11 mothers of autistic children who were 6 years of age or younger. Six of the mothers had antibodies that reacted with lymphocytes of the autistic child. Five of these six mothers had a history of pregnancy disorder. Since antigens expressed on lymphocytes are found on cells of the central nervous system and, perhaps, other tissues of the developing embryo, it is suggested that aberrant maternal immunity may be associated with the development of some cases of infantile autism. PMID- 2273014 TI - Dermatoglyphic study in autistic children and controls. AB - Dermatoglyphic patterns formed during fetal development reflect genetic or early developmental events. These patterns might provide a means for investigation of a biological basis for autism, but the results of prior studies are not conclusive. The authors undertook a study of 95 autistic children, defined by DSM-III criteria ascertained independently by three child psychiatrists. The dermatoglyphic patterns of these children were compared with several control groups, all age-matched, separated by sex, and comprising different ethnic compositions. Analysis of variance as well as chi-square methods of statistical analysis were applied. Consistency among hands, ATD angle values, total ridge counts, incidence and effects on ridge count of arches, double loops, and whorls were evaluated in this comparatively large, well-controlled group of autistic children, and all failed to support a value for dermatoglyphic analysis as a discriminant of autism. PMID- 2273015 TI - Fragile X syndrome, DSM-III-R, and autism. AB - Although reports of autistic behavior in fragile X males have been published for 8 years, there is little information about specific behaviors shown by fragile X males that are suggestive of the diagnosis of autism. The new diagnostic criteria for autistic disorder contained in the DSM-III-R provided the opportunity for more closely investigating the topography of autistic behavior in 17 fragile X males and the effects of age and IQ on its occurrence. The criteria most frequently met by these subjects were related to deficits in social interaction with peers, abnormalities in verbal and nonverbal communication, stereotypic motor behavior, and unusual responses to sensory stimuli. Fragile X subjects did not frequently show abnormalities in attachment behaviors and reciprocal interaction with caregivers. There were no discernable age or IQ effects. The importance and implications of these findings are discussed and the need for greater exploration of autism "subtypes" is emphasized. PMID- 2273016 TI - Asperger's syndrome and ligamentous laxity. AB - Two autistic girls and one autistic man in whom Asperger's syndrome coexists with lifelong ligamentous laxity and muscular incoordination are described. Two had cranial circumferences at or above the 90th percentile as children, two have complex partial epilepsy, one has a colloid cyst of the third ventricle, and one had evidence of Sotos syndrome. Echocardiography was performed in the two girls and both had evidence of increased aortic compliance. It is suggested that all three suffer from a Marfan-like disorder of connective tissue and, more speculatively, that this has led to anomalous development of midline brain structures with consequent social handicaps characteristic of Asperger's syndrome. PMID- 2273017 TI - Pervasive developmental disorder in monozygotic twins. AB - Monozygotic twin brothers were diagnosed as having pervasive developmental disorder, not otherwise specified (DSM-III-R). They show different levels of cognitive and behavioral impairment, consistent with a greater number of suboptimal pre-, peri-, and postnatal factors present in one of the twins. This case study lends support to the hypothesis that genetic factors are of importance in the expression of a pervasive developmental disorder, but that degree of developmental delay, its severity, and certain clinical features may be determined by nongenetic suboptimal pre-, peri-, and postnatal events. PMID- 2273018 TI - An autistic boy copes with a terminal illness. AB - David, a 12-year-old boy with autism, developed Ewing's Sarcoma and died 3 months later. This report describes the effects of both illnesses on David, his parents, and his care givers. The difficulties encountered in finding appropriate help in the care of both illnesses and in making difficult decisions are described. The presence of autism can affect medical management and the presence of terminal illness can affect the management of autism. Suggestions are offered for effective medical and psychiatric interventions that include a sensitivity to both illnesses in physicians and other care givers; a case manager to help find appropriate medical and psychiatric services; and the availability of combined medical and psychiatric units. PMID- 2273019 TI - The role of advanced technology in inpatient child psychiatry: leading edge or useful aid? AB - New technology has played a catalytic role in advancing understanding of etiology, diagnosis, and treatment in virtually all fields of medicine. Child psychiatry, a relatively new medical specialty, has begun to employ such advanced technology in diagnosis and treatment monitoring. This current study demonstrates that, in an inpatient child psychiatric setting, such advanced technology has a positive diagnostic yield of 5% for new medical diagnoses and a cost of about 0.5% of the hospital bed cost. Other tests, such as psychotropic blood level monitoring and psychometric evaluation of cognitive functioning, have a much higher yield. PMID- 2273020 TI - Characteristics of children and adolescents in a psychiatric hospital and a corrections facility. AB - Popular opinion holds that youngsters in corrections programs are delinquents in need of reform, whereas youngsters in psychiatric settings have mental health problems and need therapy. Yet some literature suggests that youth in the two settings may not differ greatly in their mental health status. The authors compared demographic, emotional, and behavioral characteristics of youngsters placed in public psychiatric hospital and corrections settings, and they found few differences. Child Behavior Checklist scores for social competence and total problems were high and quite similar for youngsters in the two settings. White children scored significantly worse than black children on Child Behavior Checklist Internalizing, Externalizing, and total problems in corrections settings but not in the psychiatric hospital. Moreover, race was the only variable that predicted the site in which youth were placed. The findings suggest a need to study (1) the mental health needs of youngsters in nonmental health settings and (2) the procedures by which youth are assigned to service settings. PMID- 2273021 TI - Parental substance abuse and suspected child abuse/maltreatment predict outcome in children's inpatient treatment. AB - There has been relatively little empirical study of outcome for school aged children treated in psychiatric hospitals. In earlier studies, four preadmission variables were operationally defined and studied as hypothesized predictors of poor outcome in psychiatric day treatment by the criterion of recommended in-home or out-of-home placements on discharge. The preadmission variables are recent histories of severe aggression and suicidal ideation/behavior in the child and histories of parental substance abuse and reported suspicions of child abuse/maltreatment. In this study, the work has been extended to determine if these four preadmission factors relate to outcome of children treated in inpatient hospitalization. The findings indicate that the parent/family related variables, and not the child variables (nor child diagnosis), are significantly related to out-of-home recommended placements. PMID- 2273022 TI - Patient, parent, and staff attitudes toward allowing adolescent psychiatric inpatients to smoke. AB - A smoking attitude survey was developed and administered to adolescent patients, parents, and staff members at a psychiatric hospital for adolescents 6 months before and 6 months after the institution of a patient smoking ban. Attitudes before the ban were significantly more favorable toward allowing patient smoking than attitudes after the ban; smokers were significantly more in favor of allowing patient smoking than nonsmokers; and patients were significantly more in favor of allowing patient smoking than parents, who were significantly more in favor of allowing patient smoking than staff (overall ps less than 0.0001; post hoc ps less than 0.05). The findings support the feasibility of implementing smoking bans in adolescent inpatient facilities. PMID- 2273023 TI - Interpretation of transference in the psychotherapy of adolescents and young adults. AB - There is considerable controversy in the literature surrounding the role of interpretation of transference in the expressive psychotherapy of adolescents and young adults. The authors contend that interpretation of transference is often underutilized in the psychotherapy of adolescents and that many treatments could be enriched by its inclusion. It is argued that interpretation of the transference in the immediate "here and now" of the therapeutic encounter should take precedence over genetic transference interpretation, which attempts to link current attitudes toward the therapist to archaic attitudes toward the parents. Six guidelines founded on a developmental perspective are described for exploring transference themes in this age group. While interpretation of transference is neither a panacea nor uniquely mutative with adolescents and young adults, the authors believe it has an important role to play in expressive psychotherapy if used judiciously and with foresight. PMID- 2273024 TI - Inpatient psychiatric treatment of a young recidivist firesetter. AB - The inpatient psychiatric treatment and 1-year follow-up of a recidivist child firesetter with multiple clinical and behavioral problems is described. This case was unique due to the child's young age and both the severity and frequency of firesetting. The focus of therapy was on teaching fire safety skills and concepts to alter the child's interest in and involvement with fire. Other elements of the therapy targeted associated antisocial behavior and depression. At 1-year follow up, the child had not engaged in additional firesetting. This case highlights the need to provide a comprehensive assessment of firesetting, understand its relationship to psychopathology, and offer specialized interventions. PMID- 2273025 TI - Use of a horror film in psychotherapy. AB - Modern improvements in the technology of cinematic special effects have ushered in a new genre of vivid and graphic horror film. The numerous sequels of these films attest to their popularity among adolescents and young adults. Considerable concern has arisen on the part of parents, professionals, and policymakers regarding adverse effects of these films upon children. The authors discuss the meaning of a horror film to a troubled 13-year-old boy and describe the use of the film in his psychotherapy. The modern horror film serves many of the same functions for the adolescent that the traditional fairy tale serves for the younger child. PMID- 2273026 TI - A survey of child and adolescent psychiatry residents: perceptions of the ideal training program. AB - A survey instrument was developed to examine several issues relevant to training in child and adolescent psychiatry. Forty percent of the residents representing 56% of the training programs in the United States completed the questionnaires. A descriptive profile of the typical training experiences of child and adolescent psychiatry residents is presented, as is a report of their satisfaction with each component of their program and their expectations of an ideal training program. In general, satisfaction with residency training experiences was found to be highly related to the amount of emphasis reportedly placed on the various training experiences. The implications of the findings for training directors are discussed. PMID- 2273027 TI - Research careers in child psychiatry: an update on five NIMH workshops. AB - To foster research in child psychiatry, the National Institute of Mental Health and the American Academy of Child and Adolescent Psychiatry sponsored three workshops in 1981-82 and two others in 1984. Overall, 60 trainees and several senior researchers participated. A 30-month follow-up of the careers of 34 residents who participated in the first three workshops and a description of the workshops were published earlier. This report summarizes the nature and degree of postworkshop activities of 23 additional child psychiatrists involved in the 1984 workshops, along with the needs, problems, and sources of help that they recognized as important. Promising is the fact that the vast majority were involved in research and research training and employed in academic settings. PMID- 2273028 TI - Forensic child psychiatry. PMID- 2273029 TI - Civil litigation and the child psychiatrist. AB - This paper reviews the legal principles involved in tort litigation and covers the evolution of case law regarding recovery of damages for psychic trauma. Concepts of zone of danger, foreseeability, and proximate cause are discussed. Issues for both plaintiff and expert witness are discussed. Case examples are provided, and recommendations are made regarding the child psychiatrist's involvement in these cases. PMID- 2273030 TI - Special issues in child custody evaluations. AB - The child and adolescent psychiatrist who performs child custody evaluations assumes an extraordinary responsibility. Operating at the interface of psychiatry and the law, this forensic psychiatrist is often confronted by special factors that can make a normally complicated process even more intricate. This paper examines the forensic psychiatrist's role in dealing with a number of special issues which often arise during child custody evaluations. These issues are: the mentally ill parent, the homosexual parent, stepparents, grandparents' rights, and parental kidnapping. Case vignettes are presented, and guidance for the clinician is provided. PMID- 2273031 TI - Ethical, legal, and psychodynamic considerations in intervention of a possible cult member. AB - A 17-year-old boy is brought involuntarily by his parents for admission to an adolescent unit after running away from home to join a cult. The adolescent is admitted to the hospital for a multidisciplinary assessment. Follow-up 6 months after discharge shows the family to have continued in family therapy with the patient remaining at home with no additional contact with the cult. The case raises important ethical and dynamic issues about whom the child psychiatrist serves--the parents, the adolescent, or society. Discussion by an ethicist, lawyer, and child and adolescent psychoanalyst follows the case presentation. PMID- 2273032 TI - Chemical restraint? PMID- 2273033 TI - A tantrum test? PMID- 2273034 TI - Fluoxetine and anorexia. PMID- 2273035 TI - Fluoxetine and autism. PMID- 2273036 TI - Fluoxetine-TCA interaction. PMID- 2273037 TI - TS prognosis and ADD. PMID- 2273038 TI - Validity of the CBCL. PMID- 2273039 TI - Non-palpable cancer of the breast. PMID- 2273040 TI - Non-palpable breast cancer: the point of view of the pathologist. PMID- 2273041 TI - Mammography: the gold standard of breast mass screening. AB - The rationale and results of breast mass screening are presented. The data available suggest that annual or biannual mammography reduce breast cancer mortality and should be recommended especially to women aged 50-65. PMID- 2273043 TI - [Echography of breast cancer: review of symptoms, ultrasonic-guided punctures]. AB - The paper describes the different echographic signs of malignancy and the technique of fine needle biopsy. In a series of 220 successive cytoponctions, only one case of false negative was recorded. PMID- 2273042 TI - Radiological guidelines for the detection of early breast cancer: a review. AB - Mammography remains the major technique for detecting breast cancer. In Europe the screen-film technique is most frequently used, although the radiation dose in xeroradiography has been significantly reduced since liquid toner was introduced. The ultimate goal of mammography is to detect breast cancer at an early stage, especially through screening projects. The authors discuss the classic signs, such as calcifications and irregular shaped masses which are well known, and also the indirect signs. They insist on the necessity of having a special equipment to perform high quality views and focus on the importance of quality control. PMID- 2273044 TI - [Advantages of the 5 MHz transducer in the diagnosis of non-palpable breast cancer]. AB - We surveyed more than 800 neoplastic lesions studied by US in our department. Fifty-five were non-palpable (T0) tumors. In 60% of the cases, positivity or high suspicion of malignancy was demonstrated by US. If the doubtful cases (one sign of positivity), are added, the diagnostic rate is 67%. In the same series, X-ray mammography including positive, suspicions and doubtful cases reached the same percentage, giving together a final score of 89%. The method use is briefly described and the particular contribution of the 5 MHz mono-transducer is emphasized. The complementary of X-ray mammography and US studies in the diagnosis of T0 breast neoplasms is stressed. PMID- 2273045 TI - The value of thermography for the diagnosis, prognosis and surveillance of non palpable breast cancer. PMID- 2273046 TI - Contribution of CT to the detection of non-palpable breast cancer. PMID- 2273047 TI - Computed tomographic mammography: diagnostic approach to breast cancer. PMID- 2273048 TI - [Diaphanography of the breast: myth or reality?]. AB - The old method of diaphanoscopy or transillumination is generally considered by most physicians to be as non-invasive as it is needless. However, since the beginning of the eighties, thanks to the video camera, the computer, the use of red and infrared lights, new modes of application of this method have been possible; i.e. diaphanography, light scanning, diaphanoscopy, in vivo spectrometry. Two fields of indications for diaphanography are now evaluated: 1) In breast cancer detection and diagnosis, interesting results are claimed. The discussion about the comparison of these results with those of mammography may be long and hard. 2) In the evaluation of the richness of the structures of the breast, diaphanography offers unique possibilities. It has a special ability for the detection of local or general hyperplasia which is positively correlated with the risk of cancer. It may be too early to appreciate with certainty the value of these new modes of application of diaphanography, but its theoretical background shows that it is able to offer original information. Therefore, considering the difficulties and the importance of the diagnosis of breast diseases and the limits of the methods today in use, we should feel compelled to develop this examination procedure. PMID- 2273049 TI - The role of stereotaxic fine needle biopsy in non-palpable breast lesions. PMID- 2273050 TI - Prebiopsy localization of non-palpable breast cancer. AB - Mammographic screening results in the detection of non-palpable breast lesions which demand surgical excision after careful marking by the radiologist. The main localization procedures are described as well as their preferential indications. Stereotaxic localization and harpoon technique are analysed more in detail and so are their advantages and inconvenients. Continuous research for the best compromise patient tolerance/efficiency/costs of the method remains an absolute necessity. To this regard the use of a carbon material suspension described in 1983 by Svane appears to be a really interesting and promising preoperative tracer. PMID- 2273051 TI - [Radiological monitoring of breast cancer following conservative treatment]. PMID- 2273053 TI - Non-palpable breast cancer. PMID- 2273052 TI - Breast conserving treatment for early cancers. Rationales, perspectives and techniques. AB - The paper reviews the rationale for breast conserving treatment for early cancers; the different studies are presented as well as the technical limitations and problems involved by surgery and radiotherapy. Nowadays, breast conserving treatment includes a limited resection of the tumor followed by a course of radiation. This treatment allows to preserve the breast and spares a mutilation to the woman. It requires an early diagnosis of the disease, stressing the need for a well-designed screening program. PMID- 2273054 TI - Platelet-derived growth factor-induced destabilization of smooth muscle alpha actin mRNA. AB - We have previously shown that treatment of postconfluent, quiescent rat vascular smooth muscle cells (SMC) with platelet-derived growth factor (PDGF) dramatically reduced smooth muscle (SM) alpha-actin synthesis and SM alpha-actin mRNA abundance, suggesting a role for this mitogen in the control of SMC differentiation. In the present studies, we explored the molecular mechanisms whereby PDGF decreases SM alpha-actin mRNA levels. Treatment of postconfluent SMC with both platelet PDGF and recombinant PDGF-BB resulted in a dramatic and concentration-dependent decrease in SM alpha-actin mRNA levels. We observed no differences in efficacy between platelet PDGF and PDGF-BB, indicating that the PDGF-A chain is not required for the effect. The rate of decrease in SM alpha actin mRNA abundance in PDGF-treated SMC was greater than that observed in cells treated with the transcriptional inhibitor, actinomycin D, with or without PDGF, indicating that PDGF induced a transcriptionally dependent destabilization of the cytosolic SM alpha-actin mRNA pool. This effect appeared selective for SM alpha actin, in that there was no evidence of a similar change in non-muscle (NM) beta actin mRNA stability following PDGF treatment. Results of nuclear run-on analyses showed no differences in SM alpha-actin transcription between PDGF- and vehicle treated SMC at either 4 or 24 hours following treatment, demonstrating that decreases in transcription of the SM alpha-actin gene did not contribute to PDGF induced changes in SM alpha-actin mRNA abundance. Results of these studies support a possible role for PDGF in regulation of SMC differentiation via a post transcriptional control mechanism. PMID- 2273055 TI - M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3. AB - We have isolated a subline of the M-07 human megakaryoblastic leukemia cell line, designated M-07e, that requires either interleukin-3 (IL-3) or granulocyte macrophage colony-stimulating factor (GM-CSF) for growth, even in the presence of fetal calf serum. This cell line will not grow long term in any other cytokine although it responds slightly to IL-2, IL-4, IL-6, IL-9, and interferon-gamma. We have used the M-07e subline to develop a quantitative bioassay for the measurement of levels of either GM-CSF or IL-3. This assay is as sensitive to either factor as the human bone marrow colony assay (CFU-GM) or the chronic myelogeneous leukemic (CML) blast cell proliferation assay for these factors and is much more convenient and reliable than either. With this assay, as little as 25-50 pg/ml of either IL-3 or GM-CSF can be detected, a level that should render the assay useful for analysis of these molecules in samples from patients undergoing colony-stimulating factor therapy and from conditioned media from natural sources of the factors. In these cases, neutralizing antisera to each cytokine are required to demonstrate the specificity of the assay. This assay, in combination with quantitative immunoassays, should greatly facilitate the analysis of the roles of IL-3 and GM-CSF in regulating hematopoiesis both in patients and in natural sources of the cytokines. PMID- 2273056 TI - Evidence for c-myc in the signaling pathway for TGF-beta in well-differentiated human colon carcinoma cells. AB - Previously, we described a model culture system for comparing responsiveness of poorly differentiated and well-differentiated human colon carcinoma cells to exogenous growth factors. While polypeptide growth stimulators elicited an up regulation of c-myc, as well as a mitogenic response in the well-differentiated cells, the poorly differentiated cells were insensitive to exogenous growth stimulators. We now show, by thymidine incorporation experiments and autoradiographic analysis, that transforming growth factor beta 1 (TGF-beta) abrogated the mitogenic responses to the growth factors epidermal growth factor + insulin + transferrin (IC50 = 0.8 ng/ml), as well as to nutrients (basal medium; IC50 = 0.2 ng/ml) in the well-differentiated cells. The poorly differentiated cells did not respond to TGF-beta. Moreover, TGF-beta (10 ng/ml) completely abrogated the growth factor-stimulated up-regulation of c-myc in the TGF-beta responsive, well-differentiated colon carcinoma cells. Addition of TGF-beta to the TGF-beta-responsive, well-differentiated cells, at a time after c-myc had been transiently up-regulated in response to growth stimulatory factors, resulted in a loss of responsiveness to TGF-beta. Addition of TGF-beta to these cells at increasing time periods after EIT stimulation also resulted in a loss of the TGF beta-induced repression of c-myc. The results suggest an important role for c-myc in the mechanism of action of TGF-beta in well-differentiated human colon carcinoma cells. PMID- 2273057 TI - Complex mitogenic requirements of Na(+)-K(+)-Cl(-)-cotransport-deficient BALB/c 3T3 cells. AB - The ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) to stimulate mitogenesis in BALB/c-3T3 cells and in a Na+K+Cl(-)-cotransport-defective variant subclone was investigated. This transport variant had previously been reported to be TPA mitogenically nonresponsive (O'Brien and Prettyman: Journal of Cellular Physiology 130:377-381, 1987) since the addition of TPA to the spent medium of density-arrested cultures stimulated DNA synthesis in the parent but not the variant cell line. We now report that the addition of TPA plus insulin, either directly to the spent medium or together with fresh medium, stimulated DNA synthesis in both the parent and variant cells to approximately the same extent. The parent and transport-deficient cells differed, however, in their sensitivity to the co-mitogenic effects of insulin or insulin-like growth factors. PMID- 2273058 TI - Binding of epidermal growth factor to its receptor is affected by membrane phospholipid environment. AB - Cells of epithelial origin generally require ethanolamine to grow in culture; when these cells are grown without ethanolamine, the phosphatidylethanolamine content of their membrane phospholipid becomes 1/2 to 1/3 of the normal amount, and growth stops. We have hypothesized that growth ceases because the phospholipid environment becomes unsuitable for membrane-associated function. Using ethanolamine-requiring rat mammary cells, we have investigated the possible effect of phosphatidylethanolamine deficiency on the binding characteristics of epidermal growth factor. Apparent dissociation constant for the high-affinity sites in cells having normal membrane phospholipid was 1.7 X 10(-10) M, whereas that of phosphatidylethanolamine-deficient cells was 2.7 X 10(-10) M: the difference was small, but significant. Pretreatment with phorbol ester caused the loss of high-affinity sites in cells having normal membrane, whereas binding characteristics of epidermal growth factor became refractory to the pretreatment in phosphatidylethanolamine-deficient cells. In addition, the rate of internalization of bound epidermal growth factor in phosphatidylethanolamine deficient cells was about 1/4 of normal cells. Further, whether cells had normal or phosphatidylethanolamine-deficient membranes seemed to affect the phosphorylation patterns of membrane proteins in response to epidermal growth factor or phorbol ester. These results suggest that membrane phospholipid environment affects the activity of the epidermal growth factor receptor. PMID- 2273059 TI - Differential modes of action of fibronectin and epidermal growth factor on rabbit corneal epithelial migration. AB - In order to clarify the roles of fibronectin (FN) and epidermal growth factor (EGF) in corneal wound healing, we cultured blocks of excised rabbit cornea for 24 hours in media containing one of these agents, then measured the length of the path of the epithelial layer that had migrated down the side of the block. Both FN and EGF stimulated epithelial migration significantly in a dose-dependent fashion. Responses to EGF involved a time lag of at least 12 hours before stimulation could be observed, but there was no lag-time for FN-stimulated migration. FN was maximally effective only if it was continuously present. In contrast, exposure to EGF for 6 hours did not stimulate epithelial migration, but exposure for 9 hours resulted in the same stimulatory effects as were observed after 24 hours' continuous exposure. Anti-FN antibody inhibited the FN- and EGF stimulated migration of corneal epithelium. But anti-EGF antibody inhibited only EGF-stimulated migration and had no effect on FN-stimulated migration. These results indicate that, unlike FN, EGF need not be present, once the epithelial cells have recognized its signal. Furthermore, the stimulatory effect of EGF depended on FN, while that of FN was independent of EGF. The effects of EGF on migration of corneal epithelium may, therefore, be mediated by FN. PMID- 2273060 TI - Effect of polyunsaturated fatty acids and phospholipids on [3H]-vitamin E incorporation into pulmonary artery endothelial cell membranes. AB - Vitamin E, a dietary antioxidant, is presumed to be incorporated into the lipid bilayer of biological membranes to an extent proportional to the amount of polyunsaturated fatty acids or phospholipids in the membrane. In the present study we evaluated the distribution of incorporated polyunsaturated fatty acids (PUFA) and phosphatidylethanolamine (PE) in various membranes of pulmonary artery endothelial cells. We also studied whether incorporation of PUFA or PE is responsible for increased incorporation of [3H]-vitamin E into the membranes of these cells. Following a 24-hr incubation with linoleic acid (18:2), 18:2 was increased by 6.9-, 9.2-, and 13.2-fold in plasma, mitochondrial, and microsomal membranes, respectively. Incorporation of 18:2 caused significant increases in the unsaturation indexes of mitochondrial and microsomal polyunsaturated fatty acyl chains (P less than .01 versus control in both membranes). Incubation with arachidonic acid (20:4) for 24 hr resulted in 1.5-, 2.3-, and 2.4-fold increases in 20:4 in plasma, mitochondrial, and microsomal membranes, respectively. The unsaturation indexes of polyunsaturated fatty acyl chains of mitochondrial and microsomal membranes also increased (P less than .01 versus control in both membranes). Although incubations with 18:2 or 20:4 resulted in several-fold increases in membrane 18:2 or 20:4 fatty acids, incorporation of [3H]-vitamin E into these membranes was similar to that in controls. Following a 24-hr incubation with PE, membrane PE content was significantly increased, and [3H] vitamin E incorporation was also increased to a comparable degree, i.e., plasma membrane greater than mitochondria greater than microsomes. Endogenous vitamin E content of the cells was not altered because of increased incorporation of PE and [3H]-vitamin E. When [3H]-vitamin E was incorporated into lipid vesicles prepared from the total lipid extracts of endothelial cells and varying amounts of exogenous PE, vitamin E content was directly related to PE content. These results demonstrate that PUFA and PE distribute in all pulmonary artery endothelial cell membranes. However, only increases in PE were associated with increased incorporation of [3H]-vitamin E in membranes of these cells. PMID- 2273061 TI - Improved coupling between proliferation-arrest and differentiation-induction in ML-1 human myeloblastic leukemia cells. AB - Proliferation and differentiation are coupled in normal cells and are aberrant in leukemia cells. The studies reported here were aimed at more effectively coupling proliferation-arrest and differentiation-induction in a human myeloblastic leukemia cell line (ML-1). This was accomplished by using reduced serum conditions in conjunction with a differentiation-inducing agent: cells were first incubated in reduced serum [0.3% fetal bovine serum (FBS)] instead of standard conditions (7.5% FBS) and, second, exposed to 12-O-tetradecanoylphorbol-13 acetate (TPA). The effects of this protocol were as follows: first, cell proliferation was slowed and cells accumulated in G0/G1 phase of the cell cycle; this occurred with only a minimal decrease in viability [to approximately 88-92% (0.3% FBS) from greater than or equal to 96% (7.5% FBS)]. Second, the induction of differentiation was accelerated; this allowed the time of exposure to TPA to be decreased. Acceleration of induction was very pronounced when cells were maintained in 0.3% FBS both before and during exposure to TPA, with TPA at concentrations above the minimum sufficient for induction but below those causing significant cytotoxicity; as little as 1 hour of TPA exposure resulted in near maximal induction (approximately 80%) with this protocol, compared to the greater than or equal to 1 day required with previous standard protocols. In sum, conditions that slow ML-1 cell proliferation (0.3% FBS) enhance TPA-induced differentiation, substantially narrowing the time frame of induction; these conditions should be useful for studying the molecular mechanisms that underlie the induction process. PMID- 2273062 TI - Coupling HPLC to GC: why? How? With what instrumentation? AB - Coupling LC to GC alleviates sample preparation in the sense of preseparation, cleanup, or enrichment and replaces conventional methods such as column liquid chromatography, enrichment by or filtration through sample preparation tubes, preparative thin-layer chromatography, or liquid-liquid partitioning. LC is more efficient in separation power, more rapid, and allows fully automatic integration of sample preparation into GC. Advantages are discussed for selected applications. The transfer techniques, as well as some key requirements for an LC GC instrument, are briefly summarized. PMID- 2273063 TI - Determination of deoxynivalenol (DON, vomitoxin) in wheat by high-performance liquid chromatography with photolysis and electrochemical detection (HPLC-hv-EC). AB - Deoxynivalenol (DON, vomitoxin) is a naturally occurring toxic fungal metabolite found in grains such as wheat, corn, rye, and barley. Current methods of analysis for DON and related trichothecene mycotoxins involve gas chromatography with electron capture detection, thin-layer chromatography, and high-performance liquid chromatography with ultraviolet detection. Improved sensitivity and selectivity for DON, as well as for the related compounds nivalenol and fusarenon X, are made possible by the use of high-performance liquid chromatography with online, postcolumn photolysis and oxidative amperometric detection (HPLC-hv-EC). Conditions are optimized with respect to residence time in the photolytic reactor, applied potentials, mobile phase pH, and chromatographic parameters for the separation of DON, nivalenol, and fusarenon-X, and the technique is found to be linear over a range of 10 ppb-2 ppm with minimum detection limits on the order of 1-2 ng on-column (10-20 ppb). Since these compounds are not electroactive in the absence of photolysis, an additional mode of specificity is realized in addition to the chromatographic retention time and the dual-electrode response ratio. Some market samples of wheat naturally contaminated with DON are analyzed by this method, and the results are in agreement with those obtained by HPLC-UV and TLC analyses of the same samples. PMID- 2273064 TI - Determination of aliphatic amines in air by on-line solid-phase derivatization with HPLC-UV/FL. AB - An easy, rapid, and efficient method using on-line solid-phase derivatization in HPLC is developed for the trace determination of aliphatic amines in air. Some fundamental studies on stop-flow, on-line, solid-phase derivatizations in HPLC are also investigated, such as optimization of the reaction detection HPLC system and band broadening. Air is sampled with silica gel tubes from different sites, including sewage areas, fish cleaning and processing rooms, and an organoleptic lab of the U.S. Food & Drug Administration (FDA). The trapped amines are desorbed with an acidic aqueous-organic solution, followed by pH adjustment of the eluates to pH 10. The resulting solution is directly injected into an on-line, precolumn, solid-phase derivatization and reversed-phase HPLC-UV/FL system, not requiring any further sample workup steps. The percent derivatizations are as high as 88 +/ 5% (n = 3) for primary amines, and 75 +/- 4% (n = 3) for diethylamine under optimized conditions (60 degrees C for 10 min). The recoveries for all amines are above 90%. The method is validated by a single-blind, spiked experiment with 1.1 4.4% relative standard deviation (RSD) in the range of 15-47 ppm. These results are confirmed by a GC-FID method performed in another lab. Amines are quantitated via calibration plots, with final concentrations from 0.02 to 0.38 mg/m3 air. It is suggested that this newer approach for the determination of amines and polyamines, using polymeric solid-phase reagents on-line, precolumn in HPLC, should prove generally successful for other amines and other sample types in the future. PMID- 2273065 TI - Solid sorbent collection and gas chromatographic determination of bis(2 chloroethyl)sulfide in air at trace concentrations. AB - This article describes a method for the quantitative determination of the toxic military agent bis(2-chloroethyl)-sulfide (or sulfur mustard) in air or other similar gases at parts-per-trillion levels. The method entails the adsorptive trapping of mustard vapor on a bed of Tenax-GC, followed by the transfer of trapped mustard to a smaller sorbent bed and the thermal desorption of the mustard into a gas chromatograph equipped with a flame photometric detector. Interference from an oxidizing gas (probably NO2) in the air is circumvented by sampling through a filter impregnated with triethanolamine (TEA) which selectively attenuates the NO2 while transmitting the mustard. The method is found to possess adequate accuracy and precision for most purposes, and the detection limit is observed to depend on the magnitude of the sample or sorbent background response rather than on instrument noise, adsorptive sampling capacity, or other fundamental limitations of the hardware. PMID- 2273066 TI - HPLC-photolysis-electrochemical detection in pharmaceutical analysis: application to the determination of spironolactone and hydrochlorothiazide in tablets. AB - To extend the applicability of electrochemical detection in pharmaceutical analysis, an on-line postcolumn photochemical reactor is used to produce electroactive photoderivatives of selected cardiovascular drugs. This system is applied to the analysis of dosage forms containing spironolactone in both single component formulation and in combination with hydrochlorothiazide. The pH of the mobile phase and irradiation time within the reactor are optimized to produce maximum amperometric response. Spironolactone, hydrochlorothiazide, and 4-amino-6 chloro-1,3-benzenedisulfonamide, the synthetic precursor and hydrolysis product of hydrochlorothiazide, are separated by reversed-phase chromatography on a 5 microns cyano bonded phase column within nine minutes by using a methanol phosphate buffer mobile phase. Minimum detectable levels are in the low ng range. PMID- 2273067 TI - Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl) 1-propanamines: regioisomers of the 3,4-methylenedioxyamphetamines. AB - The title 1-(3,4-methylenedioxyphenyl)-1-propanamines represent positional isomers of the N-substituted 3,4-methylenedioxyamphetamines, clandestinely produced drugs frequently encountered by forensic laboratories. These propanamines are prepared by reductive amination of 3,4 methylenedioxypropiophenone with a series of N-alkylamines. Analytical methods are developed to distinguish these compounds from the MDA series. The ultraviolet spectra of the propanamines are very similar to those of the MDAs with absorption maxima at 284 and 236 nm. The propanamines are separated under reversed-phase liquid chromatographic conditions by using a C18 stationary phase and a mobile phase of acidic (pH 3) acetonitrile containing methanol and triethylamine. The relative retention properties of these compounds parallel those observed in the MDA series. The electron impact mass spectra of the propanamines are determined by GC-MS, and the fragmentation pattern clearly distinguishes these compounds from those of the MDA series having the same molecular weight. PMID- 2273068 TI - Detection and quantitation of ethylene oxide, 2-chloroethanol, and ethylene glycol with capillary gas chromatography. AB - A procedure is described for detection and quantitation of ethylene oxide and two major reaction products. Detection of ethylene oxide residuals extracted from alcohol pads (cellulose) and plastic material is illustrated. Quantitation of the three compounds can be obtained with a single gas chromatographic (GC) analysis. A DB-Wax-30N, 0.25 mm i.d. column is used with 1:50 split injections with dimethylformamide as the solvent and 1:100 split injections with water as the solvent. A DB-Wax-30W, 0.32 mm i.d. column is used for on-column injections and 1:100 split water injections. Linearity of the three compounds is demonstrated. PMID- 2273069 TI - Determination of volatile organics in drinking water with USEPA method 524.2 and the ion trap detector. AB - New drinking water regulations require the monitoring of eight volatile organic compounds that have established maximum contaminant levels (MCLs) and 51 other volatile organics for which MCLs are not established. A laboratory analytical method (Method 524.2) for the determination of 58 of these compounds is investigated, and precision and accuracy data are obtained. The method uses a standard inert gas purge extraction, isolation of the volatile organics on a three-stage solid-phase trap, thermal desorption into a gas chromatograph, separation with a fused-silica capillary column, and identification and measurement with a relatively low cost, benchtop ion trap detector that functions as a mass spectrometer. At a concentration of 2 micrograms/L (2 parts per billion), the grand mean measurement accuracy for 54 compounds was 95% of the true value with a mean relative standard deviation (RSD) of 4%. At 0.2 micrograms/L (200 parts per trillion), the grand mean measurement accuracy for 52 compounds was 95% of the true value with a mean RSD of 3%. PMID- 2273070 TI - The identification and quantitation of alkylated nucleobases by high-performance liquid chromatography with UV photodiode array detection. AB - The application of UV diode array detection in high-performance liquid chromatographic (HPLC) identification and quantitation of several classes of synthetic and commercially available alkylated nucleobases is investigated. Quantitative spectral overlays of these compounds to methyl standard references from a spectral library and absorbance ratios at two maximal wavelengths (lambda max) are found to be useful in categorizing the solutes. They can be grouped into classes of compounds originating from a specific nucleobase and classes of analogs having different alkyl substituents (e.g., methyl, ethyl, propyl, allyl, and benzyl) at the same position of the heterocycle. At a selected wavelength for alkylated nucleobases in the same class, the detector response factors are independent of the alkyl group (+/- 10%). This technique provides a practical means for both qualitative and quantitative analysis of product distribution of DNA base alkylation by using only readily obtainable methylated derivatives as the reference standards. PMID- 2273071 TI - Liquid chromatographic properties and aqueous solution stability of N-hydroxy-3,4 methylenedioxyamphetamine. AB - The reversed-phase liquid chromatographic properties of N-hydroxy-3,4 methylenedioxyamphetamine (NOHMDA) were determined on a C8 stationary phase specifically prepared for the separation of basic compounds. NOHMDA and several N alkyl MDA derivatives displayed excellent peak shape on this stationary phase without the need for competing bases such as triethylamine. The k' values for NOHMDA varied with mobile phase pH in the range of 2.5 to 6.0, but the retention of the primary amine, MDA, and N-alkyl MDAs remained relatively constant over this range. The pKa value for NOHMDA was determined by titration to be 6.22 compared to a pKa of 10.04 for MDA. Thus, the variation of k' with mobile phase pH for NOHMDA may be a result of appreciable changes in degree of protonation. The stability of NOHMDA was found to decrease with an increase in aqueous solution pH. At pH 7.0 the degradation half-life was determined to be 49.8 h, which decreased to 2.57 h at pH 10.0. Above pH 10.0 the decomposition to the corresponding oxime was too fast for a reliable half-life determination. PMID- 2273072 TI - Comparison of panic symptom sequences and pathophysiologic models. AB - In an attempt to assess which of the proposed etiologic models best accounts for the symptomatology seen in panic attacks, 21 patients with panic attacks were asked to describe the symptom sequence during an attack. Using the Kolmogorov Smirnov test, the Runs test, and Friedman's 2-way ANOVA, the degree of agreement between their attacks, and the proposed models was assessed. All three analyses suggest that, at the 0.1, 0.025, and 0.05 levels of significance respectively, the autonomic dysfunction model best accounts for the sequence of symptoms in panic attacks. PMID- 2273073 TI - The effects of behavioral parent training on families with young hyperactive children. AB - We sought to assess, through two case-studies, the strengths and limitations of a time-limited, family-based behavioral intervention for preschool-aged children with attention-deficit-hyperactivity disorder (ADHD). The families completed a ten week child management training program and attended a number of follow-up sessions. Changes in parent and child functioning were assessed with a variety of rating scales, interviews, and data collected by parents at home on targeted behavior problems. Improvements were found in parents' confidence in their child management ability and knowledge of behavioral principles, in certain child behavior problems, in parental ratings of hyperactivity, and in the parent-child relationship. Implications of the findings for the treatment of young children with hyperactivity are discussed. PMID- 2273074 TI - Theoretical weakness in behavior theory is no more than statistical variance: a response to Christina Lee. PMID- 2273075 TI - Behavior analysis, cognitive therapy, and covert conditioning. AB - Branch (The Behavior Therapist 10, 79-84, 1987) and others have expressed interest in extending the behavior analytic framework into the realm of behavior therapy and private events. We point out that several imagery-based behavior therapy procedures such as systematic desensitization, implosive therapy, and covert conditioning were designed to be employed according to learning principles and that covert conditioning is specifically based on principles of operant conditioning. Since the covert conditioning model already combines the advantages of behavior analysis, behavior therapy, and imagery, covert conditioning, rather than cognitive therapy, should be considered by behavior analysts seeking ways to study and modify both private and public events. PMID- 2273076 TI - Prophylactic effects of psychoanalysis on cancer-prone and coronary heart disease prone probands, as compared with control groups and behaviour therapy groups. AB - It has been shown repeatedly that behaviour therapy fulfils a useful prophylactic function in the prevention of cancer and coronary heart disease. The present study investigates the effects of orthodox psychoanalytic treatment on the eventual probability of death from cancer and coronary heart disease in probands treated by psychoanalysis for over two years, probands who broke off psychoanalytic treatment after less than two years, and various control groups. Psychoanalysis is shown to have a significantly negative effect on survival after seven years follow-up. PMID- 2273077 TI - A perspective on the American Board of Clinical Pharmacology, Inc. PMID- 2273078 TI - Ambulatory blood pressure monitoring: a new window to clinical therapeutic decisions in hypertension. PMID- 2273079 TI - Incorporation of clinical pharmacology into the fourth year of the medical curriculum: teaching clinical pharmacology without a clinical pharmacologist. AB - In congruence with the educational goals of the institution, the pharmacology department has developed courses for senior students. By using the students' recently acquired clinical knowledge, these courses amplify material from the core course in pharmacology. Engaging students in this type of course requires significant commitment from the faculty involved and also from the dean and department chairman. This course has outlasted many curricular changes and has remained in the mainstream of medical education. Goals of this course remain consistent with current proposals to develop new directions in medical education. PMID- 2273080 TI - Antihypertensive efficacy of guanfacine and prazosin in patients with mild to moderate essential hypertension. AB - Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with chlorthalidone 25 mg every morning (phase II), and an 8-week double-blind treatment period with diuretic plus prazosin or guanfacine (phase III). Those who had an average seated diastolic blood pressure (BP) of 95 to 114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus either guanfacine, 1 mg every night, or prazosin, 1 mg three times a day. Of the 102 patients who were randomly assigned to guanfacine or prazosin, 80% completed the entire study. Guanfacine and prazosin appeared to be equally effective and reduced seated as well as standing diastolic and systolic BP. The mean seated systolic and diastolic BP were reduced 11/9 mm Hg by guanfacine and 11/10 mm Hg by prazosin. The mean reduction in seated pulse was 3 beats/minute for guanfacine and no change with prazosin. Similar changes occurred in the standing position. Very few adverse effects were reported during the study. Adverse effects with an incidence of 5% or greater for either drug group were dizziness (6% guanfacine, 8% prazosin), xerostomia (6% guanfacine, 2% prazosin), and somnolence (0% guanfacine, 6% prazosin). Three patients (6%) in the prazosin group experienced symptoms of orthostasis requiring premature discontinuation of the drug and termination from the study. PMID- 2273081 TI - Pharmacodynamic action and pharmacokinetics of moxonidine after single oral administration in hypertension patients. AB - Moxonidine is a new centrally acting alpha 2-adrenoceptor agonist that differs from others by a lower incidence of side effects in hypertensive patients. The effects of moxonidine and placebo on blood pressure, pulse rate, plasma catecholamines, plasma renin activity, sedation, and salivary flow were evaluated in eight hypertensive patients by an intraindividual comparison. Moxonidine induced a significant decrease in blood pressure that corresponded with its plasma concentrations. The maximum antihypertensive effect appears to be delayed when compared with the peak plasma level. Plasma norepinephrine, epinephrine, and plasma renin activity were significantly reduced by moxonidine, and blood pressure reduction corresponded with decrease of plasma norepinephrine. Heart rate, sedation, and salivary flow were not different using moxonidine compared with placebo. Only one patient mentioned dry mouth. No further relevant adverse effects were seen in the patients. This study demonstrates a significant decrease of blood pressure, plasma renin activity, norepinephrine, and epinephrine with a single dose of 0.25 mg moxonidine, but no significant effect on pulse rate, salivation, and sedation. PMID- 2273082 TI - Effects of methyldopa on psychometric performance. AB - Double-blind, crossover comparisons of methyldopa with placebo were performed in 16 patients with mild to moderate hypertension. Methyldopa (250 mg tid) for 14 days significantly reduced blood pressure, impaired card-sorting time and digital symbol substitution score, and caused trends for impairment of other psychometric tests. Effects of practice were greater than those of treatment on all tests other than card sorting, although no interaction between treatment and practice was seen. Continued dosage impairs psychometric performance, but practice effect is a major confounder. Simple crossover studies are inadequate for detecting moderate drug effects on intellectual performance. PMID- 2273083 TI - Long-term therapy with benazepril in patients with congestive heart failure: effects on clinical status and exercise tolerance. AB - Benazepril hydrochloride (CGS 14824A) is an orally active, nonsulfhydryl compound that is transformed in vivo to a long-acting inhibitor of angiotensin-converting enzyme (ACE). Previous studies have shown benazepril to lower blood pressure in hypertensive patients and to confer acute hemodynamic benefits in patients with congestive heart failure (CHF). In the current multicenter investigation, 16 patients with chronic CHF due to left ventricular systolic dysfunction (ejection fraction less than 0.40 at rest) whose symptoms corresponded to New York Heart Association classes II to IV were given open-label benazepril once daily in ascending doses of 2 to 20 mg and followed biweekly for 12 weeks. Evaluation of the 15 subjects who completed the trial showed a progressive increase in treadmill exercise duration (from 7.65 +/- 3.64 [SD] minutes at baseline to 9.74 +/- 3.66 minutes at 12 weeks, P less than .001); augmentation of the mean left ventricular ejection fraction (from 0.266 +/- 0.133 at baseline to 0.292 +/- 0.136 at 12 weeks, P less than .025); relief of exertional dyspnea in 7 of the 15 patients (P less than .02); and improvement in global symptomatic status in 10 of the patients (P less than .01). These responses were accompanied by a reduction in serum ACE activity of 75% (from 27.2 +/- 10.5 IU/L at baseline to 6.7 +/- 1.9 IU/L at 12 weeks, P less than .001), which was independent of dose and duration of treatment. The magnitude of ACE inhibition did not correlate with changes in the efficacy variables. Aside from two instances of symptomatic hypotension (one of which was complicated by volume depletion), the drug was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273084 TI - Effect of phenytoin on the clinical pharmacokinetics of amiodarone. AB - Five healthy male volunteers were given oral amiodarone hydrochloride, 200 mg per day for 6 1/2 weeks, to determine its effects on the pharmacokinetics of both intravenous and oral phenytoin. Predose amiodarone and N-desethylamiodarone serum concentrations were obtained weekly during weeks 2-6. Amiodarone serum concentrations (ASC) increased during weeks 2-4 and then decreased sharply during weeks 5-6 when oral phenytoin, 2-4 mg/kg/day, was co-administered. In addition, N desethylamiodarone serum concentrations (DEASC) exceeded corresponding ASC during weeks 5-6 whereas during weeks 2-4, DEASC were less than ASC. Because of the long elimination half-life for amiodarone previously reported in healthy volunteers after single doses of amiodarone and the frequent administration of amiodarone associated with this half-life, a modified equation for a continuous infusion was used to describe each subject's ASC versus time data. Pre-phenytoin ASC were fitted to an appropriate function to predict ASC during weeks 5-6 assuming no interaction. Observed versus predicted ASC were compared for weeks 5 and 6. Observed ASC during weeks 5 and 6 were (mean +/- SD) 0.25 +/- 0.09 micrograms/mL and 0.19 +/- 0.07 micrograms/mL, respectively. Corresponding predicted ASC were 0.36 +/- 0.12 micrograms/mL (P = .011) and 0.38 +/- 0.13 micrograms/mL (P = .004). These represented percent differences of 32.2 +/- 12.5% and 49.3 +/- 5.6% for weeks 5 and 6, respectively. Assuming there were no changes in the bioavailability of amiodarone during continuous administration, these findings strongly suggest induction of amiodarone metabolism by phenytoin. The clinical significance of this interaction remains to be determined. PMID- 2273085 TI - The Bayesian differential diagnosis of neutropenia associated with antiarrhythmic agents. PMID- 2273086 TI - Pharmacokinetics of quinapril and its active metabolite quinaprilat during continuous ambulatory peritoneal dialysis. AB - The pharmacokinetics of quinapril, a novel angiotensin converting enzyme (ACE) inhibitor, and its active metabolite, quinaprilat, were determined following a single 20-mg oral dose of quinapril in six patients with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD). Overall, quinapril was well tolerated by these CAPD patients, with mild and transient side effects, not unexpected in this clinical setting, which included pruritus, headache, nausea, and cough. Blood pressure reduction was observed in four of six patients, with onset reliably two to four hours after dosing and duration up to 48 hours, associated with quinaprilat concentrations in plasma above 90 ng/mL for at least 33 hours postdose. Two patients experienced significant hypotension, systolic blood pressure below 90 mm Hg, which responded promptly to oral fluid administration and/or reduction in dialysate tonicity. The pharmacokinetic profile of quinapril in these CAPD patients was not significantly different from that previously observed in healthy subjects with normal renal function and in patients with moderate to severe renal dysfunction not yet requiring dialysis (RDND). The apparent elimination half-life of quinapril was approximately one hour, with negligible dialysate excretion. The pharmacokinetic profile of quinaprilat in these CAPD patients was similar to that previously observed in patients with RDND. The elimination half-life of quinaprilat was markedly prolonged when compared to that in healthy subjects and averaged 20 hours, with only a small amount of quinaprilat excreted in dialysate (mean = 2.6% of total dose).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273087 TI - Proportion of parvalbumin-positive basket cells in the GABAergic innervation of pyramidal and granule cells of the rat hippocampal formation. AB - Recent studies have indicated that hippocampal GABAergic neurons in both the dentate gyrus and Ammon's horn contain immunoreactivity for the calcium-binding protein parvalbumin (PARV). Although the distribution of PARV-positive neurons has been previously described, detailed quantitative electron microscopic studies of the PARV-positive axon terminals in the hippocampal formation are lacking. In the present study, immunocytochemical methods were used to localize PARV-positive neurons and axon terminals to determine their similarity to GABAergic neurons. The PARV-positive cells and axon terminals are associated closely with the pyramidal and granule cell layers. In agreement with previous studies, the morphology of PARV-positive neurons is similar to that of GABAergic cells, including the basket cells of both the dentate gyrus and Ammon's horn. The PARV positive axon terminals form exclusively symmetric synapses with somata, dendrites, dendritic spines, and axon initial segments. However, these terminals represent only a portion of the total number of terminals that form symmetric synapses. Quantitative results indicate that only 32-38% of the total number of terminals forming symmetric axosomatic synapses with principal cells of the dentate gyrus and Ammon's horn are PARV positive. Together with previous findings from light microscopic double-labeling studies, these data indicate that the PARV positive terminals arise from a subpopulation of GABAergic hippocampal neurons. Finally, it is important to note that the terminal plexus of PARV-positive hippocampal axons overlaps at all postsynaptic sites with a plexus of PARV negative axons. PMID- 2273088 TI - Intracellular labeling of neurons in the medial accessory olive of the cat: I. Physiology and light microscopy. AB - This study is the first of three reports on the detailed morphology of horseradish peroxidase injected neurons in the medial accessory olive of the cat. Intracellular, in vivo recordings of olivary cells were made and their response to mesodiencephalic stimulation was tested. In 44 units a short latency action potential could be recorded, which was very suggestive of a monosynaptic excitatory pathway. The short latency response was frequently followed by a long latency (mean 188 msec) or rebound action potential. Recordings were followed by intracellular iontophoresis of horseradish peroxidase. A total of 21 neurons, all located within the medial accessory olive were chosen for morphological analysis. Cells could be divided into two categories on the basis of their overall morphological appearance. Type I cells (n = 5) had sparsely branching dendrites that radiated away from the soma and were usually found in the caudal part of the medial accessory olive. The axon usually originated from the soma. Type II cells (n = 16) were located more rostrally. They had larger cell bodies with dendrites that ramified extensively, forming a globular structure (mean diam. 338 microns). The axon usually originated from a first order dendrite. No recurrent axon collaterals were observed on either type I or II cells. Both cell types carried long and complex spiny appendages; however, they were most numerous on the second and higher order dendrites of type II cells. Since the soma of these cells is usually not found in the centre of its dendritic field, even if the cell is located in the center area of the neuropil, it is suggested that the dendritic trees of up to 100 neurons may be intricately interwoven, establishing clusters with intensive intercommunication by means of dendritic gap junctions. The abundance, length and complexity of the spiny appendages suggest an important role in this process, but may also be relevant instruments in enhancing the computational capabilities of these neurons, especially in time sensitive processes. When relating the physiological and the morphological results, it was noted that both type I and type II cells could respond to mesodiencephalic stimulation and were both able to trigger a rebound action potential. No significant correlations were found between cell size and the latency of the rebound. PMID- 2273089 TI - Intracellular labeling of neurons in the medial accessory olive of the cat: II. Ultrastructure of dendritic spines and their GABAergic innervation. AB - In order to describe the morphology of dendritic spines of identified neurons in the cat inferior olive together with their gamma-aminobutyric acid (GABA) synaptic input, a technique was used combining intracellular labeling of horseradish peroxidase with postembedding gold-immunocytochemistry. With this technique physiologically identified olivary cells were reconstructed with the light microscope, and the horseradish peroxidase reaction product and immunogold labeling were subsequently examined in serial sections at the ultrastructural level. In addition, a degenerating neuron was observed, resulting in a triple labeling in single ultrathin sections. Quantitative and three-dimensional analysis showed that the dendritic spines were composed of long, thin stalks ending in one or more spine heads. The spines of cells located in the caudal half of the medial accessory olive (type I cells, characterized by dendrites which run away from the soma) were found to be less complex than those of cells located rostrally in this olivary subnucleus (type II cells, characterized by dendrites which tend to turn back towards the soma). Most, if not all, of the spines of both cell types were located within glomeruli. On average, the spines within individual glomeruli originated from 6 different dendrites (with a maximum of 8). Different spines within the same glomerulus were never derived from different dendrites of the same olivary neuron, but single spines frequently gave rise to several spine heads, which could be located either within different glomeruli or inside a single glomerulus. The glomerular spine heads originating from the same spine were rarely located near one another. All spines and most of the spine heads were contacted by both GABAergic and non-GABAergic terminals. Most of the GABAergic terminals contained pleomorphical vesicles and displayed symmetric synapses whereas the non-GABAergic terminals showed usually round to oval vesicles and asymmetric synapses. PMID- 2273090 TI - Intracellular labeling of neurons in the medial accessory olive of the cat: III. Ultrastructure of axon hillock and initial segment and their GABAergic innervation. AB - The gamma-aminobutyric acid (GABA) synaptic input of identified axons in the cat inferior olive was studied by use of combination of intracellular labeling with horseradish peroxidase and postembedding gold-immunocytochemistry. With this technique olivary cells were physiologically identified and light microscopically reconstructed, and the horseradish peroxidase reaction product and the immunogold labeling were subsequently simultaneously visualized for electron microscopic investigation with the use of serial ultrathin sections. The axons of cell type I (characterized by dendrites which radiate away from the cell body) originated from the soma, whereas those of type II neurons (characterized by dendritic trees which curve back towards the soma) were derived from a primary dendrite. The axons of olivary neurons stand out by the length of their axon hillock (up to 21 microns) and initial segment (up to 40 microns). The hillock forms various spiny appendages which were located within glomeruli together with dendritic spines of other olivary neurons. Axonal spines of type II neurons were more numerous and complex looking than those of type I. The axonal spines, the shaft of the axon hillock, and the transition between the hillock and initial segment were primarily innervated by GABAergic terminals (65%) but non-GABAergic terminals (35%) were present as well. The terminals apposed to the axons of type I neurons contacted mainly the axonal shafts, whereas most of the terminals adjacent to the axons of type II neurons established synaptic contacts with the axonal spines. The initial segments were largely devoid of synaptic input. Distally, the initial segment acquired a myelin sheath. PMID- 2273091 TI - Gonadotropin-releasing hormone (GnRH) immunoreactive system in the brain of the dwarf gourami (Colisa lalia) as revealed by light microscopic immunocytochemistry using a monoclonal antibody to common amino acid sequence of GnRH. AB - The present paper aims to give a morphological basis for the study of the terminal nerve system and its relation to the whole gonadotropin-releasing hormone (GnRH) immunoreactive (ir) neuronal system. We examined the GnRH-ir neuronal system of a tropical fish, the dwarf gourami, by using a recently developed monoclonal antibody against GnRH (LRH13) which recognizes the amino acid sequence common to all known variants of GnRH (Park and Wakabayashi, Endocrinol. Jpn. 33:257-272, '86). The ganglion cells of the terminal nerve (TN ggl cells) in the transitional area between the olfactory bulb and the telencephalon reacted strongly with the LRH13. A distinct bundle of axons emanating from the TN-ggl cells ran caudally through the ventral telencephalon and the preoptic area. Some of these axons entered the optic nerve and innervated the retina. The remaining axons continued caudally to enter the hypothalamus and the midbrain. A second group of GnRH-ir cell bodies was found in the preoptic area. A distinct bundle of GnRH-ir fibers originating from these cell bodies innervated the pituitary. This pathway is equivalent to the preoptico infundibular pathway of other vertebrates, and the GnRH in this pathway is presumed to function as hypophysiotrophic hormone to facilitate the release of gonadotropins from the pituitary. The distribution of GnRH-ir fibers in the brain was extensive. Most fibers apparently originated from the TN-ggl cells and covered various brain regions from the olfactory bulb to the spinal cord. They were especially abundant in the olfactory bulb, ventral telencephalon, preoptic area, optic tectum, and some hypothalamic areas. Thus, GnRH might function as a neuromodulator and/or neurotransmitter in these areas. The abundant GnRH-ir fibers in the ventral telencephalon and the preoptic area might affect some aspects of sexual behavior, since these areas have been suggested to be involved in the control of sexual behavior in teleosts. PMID- 2273092 TI - The mechanoreceptive origin of insect tympanal organs: a comparative study of similar nerves in tympanate and atympanate moths. AB - A chordotonal organ occurring in the posterior metathorax of an atympanate moth, Actias luna (L.) (Bombycoidea: Saturniidae), appears to be homologous to the tympanal organ of the noctuoid moth. The peripheral anatomy of the metathoracic nerve branch, IIIN1b1 was examined in Actias luna with cobalt-lysine and Janus Green B, and compared to its counterpart, IIIN1b (the tympanal branch), in Feltia heralis (Grt.) (Noctuoidea: Noctuidae). The peripheral projections of IIIN1b1 were found to be similar in both species, dividing into three branches, the second (IIIN1b1b) ending as a chordotonal organ. The atympanate organ possesses three sensory cell bodies and three scolopales, and is anchored peripherally via an attachment strand to the undifferentiated membranous region underlying the hindwing alula, which corresponds to the tympanal region of the noctuoid metathorax. Extracellular recordings of the IIIN1b1 nerve in Actias luna revealed a large spontaneously active unit which fired in a regular pattern (corresponding to the noctuoid B cell) and smaller units (corresponding to the noctuoid acoustic A cells) which responded phasically to low frequency sounds (2 kHz) played at high intensities (83-96 dB, SPL) and also responded phasically to raising and lowering movements of the hindwing. We suggest that the chordotonal organ in Actias luna represents the evolutionary prototype to the noctuoid tympanal organ, and that it acts as a proprioceptor monitoring hindwing movements. This system, in its simplicity (consisting of only a few neurons) could be a useful model for examining the changes to the nervous system (both central and peripheral) that accompanied the evolutionary development of insect tympanal organs. PMID- 2273093 TI - Projections from the amygdala to basoventral and mediodorsal prefrontal regions in the rhesus monkey. AB - The sources of ipsilateral projections from the amygdala to basoventral and mediodorsal prefrontal cortices were studied with retrograde tracers (horseradish peroxidase or fluorescent dyes) in 13 rhesus monkeys. The basoventral regions injected with tracers included the orbital periallocortex and proisocortex, orbital areas 13, 11, and 12, lateral area 12, and ventral area 46. The mediodorsal regions included portions of medial areas 25, 32, 14, and dorsal area 8. The above sites represent areas within two architectonic series of cortices referred to as basoventral or mediodorsal on the basis of their anatomic location. Each series consists of areas that show a gradual increase in the number of layers and their delineation in a direction from the caudal orbital and medial limbic cortices, which have an incipient laminar organization, towards the eulaminated periarcuate cortices (Barbas and Pandya, J. Comp. Neurol. 286: 353 375, '89). Labeled neurons projecting to the prefrontal cortex were found in the basolateral, basomedial (also known as accessory basal), lateral, and ventral cortical nuclei, and in the anterior amygdaloid and amygdalopiriform areas. The distribution of labeled neurons differed both quantitatively and qualitatively depending on whether the injection sites were in basoventral or mediodorsal prefrontal cortices. Cases with caudal orbital injections had the most labeled neurons in the amygdala, followed by cases with injections in cortices situated medioventrally. The latter received a high proportion of their amygdaloid projections from the basomedial nucleus. The lateral amygdaloid nucleus sent a robust projection to the least architectonically differentiated orbital periallocortex, and a weaker projection to the adjoining orbital proisocortical regions, but did not appear to project to either medial proisocortical sites or to the more differentiated ventrolateral or dorsolateral prefrontal cortices. In addition, there were topographical differences in the origin of projections from one amygdaloid nucleus directed to various prefrontal cortices. These differences were correlated either with the destination of the axons of afferent amygdaloid neurons to basoventral or to mediodorsal prefrontal cortices and/or with their projection to areas with varying degrees of laminar organization within the basoventral or mediodorsal sector. The clearest topography was observed for projections originating in the basolateral nucleus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2273094 TI - Effects of visual or light deprivation on the morphology, and the elimination of the transient features during development, of type I retinal ganglion cells in hamsters. AB - Intracellular injection of Lucifer Yellow (LY) was used to study the detailed morphology of the normal visually deprived, and light-deprived superior colliculus projecting Type I retinal ganglion cells (RGCs) in hamsters. The soma size of the normal Type I cells ranged from 337 to 583 microns 2 with a mean of 436 microns 2. Two to six primary dendrites were observed in these cells. The mean dendritic field diameter was 495 microns and ranged from 309 to 702 microns. The dendritic field diameter of this population of cells exhibited an eccentricity dependence. Quantitative comparisons between the normal and visually deprived or light-deprived Type I RGCs indicated that the morphology of these three groups of cells were similar to each other in terms of the soma size, dendritic field diameter, branching pattern, and total length of the dendrites. During the normal development of cats and hamsters, several transient features, such as exuberant dendritic spines and intraretinal axonal branches, have been observed in the developing RGCs. The complete elimination of these transient features occurs at about 3 and 2 weeks after the opening of the eyes in cats and hamsters, respectively. In the present study, the hypothesis whether visual experience or light stimulation is required for the elimination of these transient features during development was examined. After studying a total of 115 mature Type I RGCs, which included cells from the normal, visually deprived and light deprived animals, no transient feature was observed. We conclude that visual or light deprivation has no effect on the morphological development of superior colliculus projecting Type I RGCs in hamsters, and the elimination of the transient features on the Type I RGCs during development does not depend on visual experience or light stimulation. PMID- 2273095 TI - Connections of the retrosplenial granular a cortex in the rat. AB - Although the retrosplenial granular a cortex (Rga) is situated in a critical position between the hippocampal formation and the neocortex, few studies have examined its connections. The present experiments use both retrograde and anterograde tracing techniques to characterize the afferent and efferent connections of Rga. Cortical projections to Rga originate in the ipsilateral area infraradiata, the retrosplenial agranular and granular b cortices, the ventral subiculum, and the contralateral Rga. Subcortical projections originate in the claustrum, the diagonal band of Broca, the thalamus, the midbrain raphe nuclei, and the locus coeruleus. The thalamic projections to Rga originate mainly in the anterodorsal (AD) and laterodorsal (LD) nuclei with sparse projections arising in the anteroventral (AV) and reuniens nuclei. Each projection to Rga terminates in distinct layers of the cortex. The thalamic projection from AD terminates primarily in layers I, III, and IV of Rga, whereas the axons arising from the LD nucleus have a dense terminal plexus only in layer 1. The projections arising from the subiculum end predominantly in layer II, whereas the postsubiculum projects to layers I and III-V. Axons from the contralateral Rga form a dense terminal plexus in layers IV and V, with a smaller number of terminals in layers I and VI. Rga projects ipsilaterally to the AV and LD nuclei of the thalamus and to the anterior cingulate, retrosplenial agranular,a and postsubicular cortices. Contralaterally it projects to the retrosplenial agranular and Rga cortices. Rga projections to the thalamus terminate ipsilaterally in the dorsal part of LD and bilaterally in AV. Together, these data suggest that Rga integrates thalamic with limbic information. PMID- 2273096 TI - Morphological and physiological characterization of small multimodal ocellar interneurons in the American cockroach. AB - The morphology and physiology of small multimodal ocellar interneurons (SM neurons) have been examined in the cockroach Periplaneta americana. The SM-neuron is monopolar with its cell body in the tritocerebrum near the esophagus. Its axon ascends to the protocerebrum and extends into the ocellar neuropil through the ocellar tract and the ocellar nerve. The axon sends a long collateral process towards the optic tract. The SM-neuron responded with spike discharges to various sensory stimuli. The collateral and many side branches along the axon in the deutocerebrum appear to be input regions from those sensory afferents. Cercal stimulation triggered most effectively a train of spikes in the SM-neuron: some of seven giant axons in the ventral nerve cord were involved in this pathway. Cercal stimulation also evoked depolarization in the large second order ocellar neurons (L-neurons). A possible neural connection between SM-neurons and L neurons was examined pharmacologically. Interaction of ocellar illumination and cercal stimulation in the L-neuron was also examined. These data are discussed in relation to the ocellar function of cockroaches and in comparison with data obtained in other insects. PMID- 2273097 TI - Morphological and physiological characterization of descending ocellar interneurons in the American cockroach. AB - In the present study two types of descending ocellar neurons have been morphologically and physiologically identified in the cockroach Periplaneta americana: a descending ipsilateral ocellar neuron (DIO-neuron) and a descending contralateral ocellar neuron (DCO-neuron). Both DIO- and DCO-neurons possess a cell body near the ocellar tract in the protocerebrum and extend dendritic processes into the ipsilateral ocellar nerve. An axon of the DIO-neuron descends to the metathoracic ganglion, and its entire course is ipsilateral to the cell body. An axon of the DCO-neuron crosses the median plane of the protocerebrum and descends through the contralateral ventral nerve cord to the second abdominal ganglion. Both axons possess masses of branches in each ganglion as well as in the brain. Both DIO- and DCO-neurons showed no spontaneous spike discharges, and responded with a few off-spikes to ocellar illumination. They responded to various mechanical stimuli, like cercal stimulation with a train of spikes which was suppressed by ocellar illumination. Spikes of DCO-neurons caused postsynaptic potentials and spikes in some interganglionic metathoracic interneurons, and spikes in motor nerves. These data are discussed in relation to the ocellar function of the cockroach as well as in comparison with that of other insects. PMID- 2273098 TI - Homotypic fetal transplants into an experimental model of spinal cord neurodegeneration. AB - Many neurotransplantation studies have dealt with the ability of solid fetal spinal grafts to develop in the previously traumatized spinal cord of a host. In neurodegenerative spinal diseases, however, motoneuronal death occurs in the absence of a trauma, i.e., in the absence of axotomy of afferent fibers. Lesioning the spinal cord with an excitotoxic agent may provide a useful neurodegenerative model. The present study has been undertaken to determine whether homotypic fetal neurons transplanted as a cell suspension are able to rebuild a neural circuitry. Emphasis is given here to the analysis of the development of transplanted motoneurons and host-graft connectivity. The lesion was made by kainic acid on the right side of the lumbar enlargement 1 week before transplantation. The fetal spinal cords were taken from rat embryos (gestational day E12-13) and transplanted as cell suspensions. Light- and electron-microscopic analysis demonstrated that the excitotoxic lesion extended over the entire spinal segment and was confined primarily to the ventral and intermediate horns, implying the death of all motoneurons with consequent paralysis and muscular atrophy of corresponding hindlimb. The lesion was characterized by a lack of neurons, glial proliferation, and sparing of fibers of passage and afferents. Two to fourteen months after surgery, the transplants were generally large, occupying most of the neuron-depleted area. The boundaries between the transplant and host tissue were clearly delineated by the higher cellular density of the graft and the particular cytoarchitecture, i.e., the cell suspension grafts did not display a laminar organization. Among the different neuronal populations within the transplant, one resembled motoneurons: large, typically Nissl-stained and immunoreactive for calcitonin gene-related peptide (CGRP). No grafted neuron, however, extended an axon into the host ventral roots. Monoaminergic afferents from the host were studied using immunostaining for serotonin, noradrenaline, and tyrosine hydroxylase. These afferent fibers, thin and varicose, grew for a long distance and formed a network within transplants. Similarly, primary sensory CGRP immunoreactive fibers (entering the graft from the dorsal host-graft interface) penetrated deeply into transplants. The response of cortico- and rubro-spinal afferents to the implantation of fetal tissue was different. After injection of WGA-HRP, a few anterogradely labeled cortical and rubral fibers entered only the most peripheral portion of transplants. In conclusion, our results indicate that fetal spinal neurons can be successfully transplanted into the adult neuron depleted spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2273099 TI - Molecular identification of the Lugaro cell in the cat cerebellar cortex. AB - The cerebellar cortex contains five major classes of neurons that can be differentiated from one another on the basis of their location, size, shape, and, in some cases, molecular characteristics. The cerebellar cortex also contains other, less numerous neuronal types, including the Lugaro cell, which has been described on only a few occasions. The Lugaro cell is a relative rare cell type and is characterized by a fusiform cell body with thick, horizontally oriented dendrites. It is located in or slightly below the Purkinje cell layer. Because the Lugaro cell shares some morphological characteristics with the other large granular layer neurons, it often has been classified as a Golgi cell. In the present study we have taken advantage of differences in the molecular properties of neurons and have used monoclonal antibodies to identify and classify the Lugaro cell. Three large neuronal types in the cerebellar cortex were examined with cell-type-specific antibodies: Cat-301 and Cat-304 for Lugaro cells; Rat-303 for Golgi cells; and anti-calbindin for Purkinje cells. Double label immunocytochemistry on sections of the cat cerebellum was performed with subclass or species-specific secondary antibodies. Each of the three antibodies was selective for one of the three large neuron classes. Cat-301 and Cat-304 recognized Lugaro cells but not Golgi or Purkinje cells. Our results demonstrate that the Lugaro cells are molecularly, as well as morphologically, distinct from Purkinje and Golgi cells and thus constitute a distinct cell type in the cerebellar cortex. PMID- 2273100 TI - An ultrastructural and morphometric study of the effect of removal of retinal input on the development of the dorsal lateral geniculate nucleus. AB - In normal development, cell layers in the dorsal lateral geniculate nucleus (dLGN) segregate from a relatively homogeneous cell group. If all retinal input is removed prior to this segregation, the layers fail to form. In the present study, we used ultrastructural and morphometric analyses to study dLGN development in the tree shrew following neonatal removal of retinal input. The goal of the present study was to determine whether there are differences between normal animals and enucleates in the development of dLGN cells and their interrelationships with each other and/or with the surrounding glia, which might explain the failure of cellular lamination in enucleated animals. The results indicate that although the development in enucleated animals may take place somewhat more slowly, by P90 cell size and density are not significantly different from normal. These results, coupled with the observation that the dLGN in enucleates is smaller than in normals, suggest that the removal of retinal input results in dLGN cell loss. At both the light and electron microscopic level, cells in the developing normal dLGN are arranged in bands of immediately adjacent cells. In enucleates, dLGN cells are less frequently in immediate contact and are arranged in small groups or clumps which may be separated by degenerating cells. The present data suggest that the presence of retinal input may be necessary to allow dLGN cells to maintain the intercellular relationships necessary for laminar segregation to take place. PMID- 2273101 TI - Primate supplementary eye field: I. Comparative aspects of mesencephalic and pontine connections. AB - WGA-HRP was used to examine projections to the brainstem from the supplementary eye field (SEF). The SEF was defined electrophysiologically in awake, behaving monkeys and connections were compared to those of the arcuate frontal eye field (FEF), area 6DC, and primary motor cortex. The SEF was found to have either direct or indirect connections with almost every known pre- and paraoculomotor structure of the brainstem. The SEF was found to project bilaterally to layers I and IV of a tangentially widespread region of the superior colliculus. Terminal label was evident in the pretectal olivary nucleus, nucleus of the optic tract, nucleus raphe interpositus (omnipause region), nucleus prepositus hypoglossi, the perioculomotor cap of the central gray, dorsal central gray, nucleus reticularis tegmenti pontis, nucleus reticularis pontis oralis, and to multiple nuclei of the basis pontis (most densely to the dorsomedial nucleus). Bilateral projections were found in the parvicellular red nucleus. Reciprocal connections were present in the nucleus limitans, the mesencephalic reticular formation, locus coeruleus, and the serotonergic nuclei of the raphe complex (dorsalis and central superior). Overall patterns of connectivity were similar to those of the FEF and markedly different from those of the contiguous dorsocaudal area 6 or primary motor cortex. It was concluded that observed patterns of SEF-brainstem connectivity further justifies viewing this region as a distinct eye field that is likely to serve preparatory and trigger functions in the generation of saccadic eye movements. PMID- 2273102 TI - Effects of cochlea removal on GABAergic terminals in nucleus magnocellularis of the chicken. AB - The effects of unilateral cochlea removal on GABA-immunoreactive (GABA-I) terminals in nucleus magnocellularis (NM) of the chick were assessed by immunocytochemical (ICC) techniques. Posthatch chicks (5-8 days old) survived from 1-37 days following unilateral cochlea removal. In the ipsilateral NM, the density of GABA-I terminals appeared to increase relative to normal controls 10 37 days after cochlea removal. However, most of that increase could be attributed to a decrease in cell size, cell number, and volume of the nucleus as a result of deafferentation. In the contralateral NM, the density of GABA-I terminals decreased relative to the ipsilateral NM and to normal animals 1-21 days after cochlea removal. The number of GABA-I terminals per NM neuron also decreased in the contralateral NM while that in the ipsilateral NM was comparable to normal controls. To ascertain whether these changes represented changes in the number of terminals or in the amount of GABA contained within the terminals, we also examined these terminals using an antibody to glutamic acid decarboxylase (GAD), the biosynthetic enzyme for GABA. Following unilateral cochlea removal, there was no difference in the density of GAD-I terminals in NM between the two sides of the brain for any of the survival times. Similarly, bilateral cochlea removal had no discernible effect on the density of GABA-I terminals in NM. These data suggest that unilateral deafferentation may temporarily downregulate the biosynthesis of GABA in the contralateral NM. PMID- 2273103 TI - Toxic epidermal necrolysis (Lyell syndrome). AB - Toxic epidermal necrolysis is perhaps the most formidable disease encountered by dermatologists. Uncommon but not rare, toxic epidermal necrolysis occurs in 60 to 70 persons per year in France. It remains as puzzling a disorder as it was 34 years ago, when described by Lyell. Whether or not toxic epidermal necrolysis is the most severe form of erythema multiforme is still the subject of discussion. The physiopathologic events that lead to this rapidly extensive necrosis of the epidermis are not understood. Indirect evidence suggests a hypersensitivity reaction, but the search for potential immunologic mechanisms has resulted in little data to support this hypothesis. Accumulated clinical evidence points to drugs as the most important, if not the only, cause of toxic epidermal necrolysis. Sulfonamides, especially long-acting forms, anticonvulsants, nonsteroidal anti-inflammatory agents, and certain antibiotics are associated with most cases of toxic epidermal necrolysis. Many other drugs have been implicated in isolated case reports. All organs may be involved either by the same process of destruction of the epithelium as observed in the epidermis or by the same systemic consequences of "acute skin failure" as seen in patients with widespread burns. Sepsis is the most important complication and cause of death. Approximately 20% to 30% of all patients with toxic epidermal necrolysis die. Elderly patients and patients with extensive lesions have a higher mortality rate. Surviving patients completely heal in 3 to 4 weeks, but up to 50% will have residual, potentially disabling ocular lesions. The prognosis is improved by adequate therapy, as provided in burn units, that is, aggressive fluid replacement, nutritional support, and a coherent antibacterial policy. Corticosteroids, advocated by some in high doses to halt the "hypersensitivity" process, have been shown in several studies to be detrimental and should be avoided. PMID- 2273104 TI - Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease. AB - The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells. PMID- 2273105 TI - GB3 monoclonal antibody for the diagnosis of junctional epidermolysis bullosa: results of a multicenter study. AB - GB3 monoclonal antibody detects a normal basement membrane component (GB3 antigen) that is variably expressed in junctional epidermolysis bullosa. To assess the accuracy of GB3 in the diagnosis of junctional epidermolysis bullosa, we have reviewed its use in 250 cases of the major types of epidermolysis bullosa. In the majority of cases of the simplex and dystrophic forms of epidermolysis bullosa, GB3 antigen is normally expressed. In the Herlitz variant of junctional epidermolysis bullosa, GB3 antigen expression is consistently abnormal, but in the non-Herlitz and indeterminate forms of junctional epidermolysis bullosa, 40% of cases express GB3 antigen normally. We propose that GB3 monoclonal antibody is useful in the accurate identification of patients with Herlitz junctional epidermolysis bullosa and may prove equal to electron microscopy for the diagnosis of this disease. For the non-Herlitz variants, it should not be used as an alternative to electron microscopy but may be of special value in the determination of prognosis. PMID- 2273106 TI - Cyclosporine in the treatment of cutaneous T cell lymphoma. AB - We present our observations on the use of cyclosporine in the treatment of three patients with mycosis fungoides and two patients with Sezary syndrome. The patients with mycosis fungoides showed mild improvement of short duration. One patient with Sezary syndrome had significant improvement during 2 years of treatment. It is unlikely that cyclosporine alone will be sufficient therapy for cutaneous T cell lymphoma. However, lower doses in conjunction with other immunomodulators may minimize potential side effects and lead to longer lasting clinical improvement. PMID- 2273107 TI - Recreational sun exposure in Puerto Rico: trends and cancer risk awareness. AB - Persons who sunbathe or engage in other activities at the beach are exposed to large amounts of UV radiation. Four hundred seven adults who visited the beaches of Puerto Rico were surveyed to determine their knowledge about the risks of sun exposure and to evaluate sunscreen use. The group consisted of 195 year-round Puerto Rican residents and 212 tourists. Ninety-five percent believed that the sun can cause skin cancer, although only half of the subset who lived all year in Puerto Rico believed that they personally received enough exposure to be at risk. The majority of the group (83%) understood the meaning of the sun protection factor numbers, although 35% used either nothing or a nonscreening oil. Half of Puerto Rican residents rarely or never used sunscreen protection while sunbathing. When sunscreen was used, the most important factor sought was given as sun protection factor (64%), followed by a perceived ability to aid in tanning (26%). PMID- 2273108 TI - Cutaneous angiolipoleiomyoma. AB - We describe eight cases of cutaneous angiolipoleiomyoma, a rare tumor previously reported only once under the term cutaneous angiomyolipoma. Clinically, the tumors were acquired, solitary, asymptomatic nodules that were always acral in location. Patients' ages ranged from 33 to 77 years (median 52.6 years); the male/female ratio was 7:1. Signs of tuberous sclerosis or renal angiomyolipoma were absent in all cases. Histologically, the tumors were subcutaneous, well circumscribed, and composed of smooth muscle, vascular spaces, connective tissue, and mature fat. In some tumors the fat was the predominant component, and in others smooth muscle predominated. Elastic tissue stains revealed that some blood vessels had developed an elastic lamina whereas other blood vessels lacked it. Additional histologic features occasionally observed included vascular thrombi, glomus bodies, and focal mucin deposition. PMID- 2273109 TI - Complete follow-up and evaluation of a skin cancer screening in Connecticut. AB - On May 21, 1988, 251 persons were screened for skin cancer in New Haven, Connecticut. A total body skin examination was performed on 98% of the participants. On the basis of follow-up of 93% of persons with positive screens for basal cell carcinoma, squamous cell carcinoma, or Bowen's disease, positive predictive values were 43% for basal cell carcinoma, 14% for squamous cell carcinoma, and 50% for Bowen's disease. In the group with atypical nevi, a person with two or more clinically atypical nevi was 16 times more likely to have histologic confirmation than a person with a single clinically atypical nevus (p = 0.003). Eighty persons were screened by both a dermatologist and a dermatology nurse; the crude agreement rate for actinic keratoses was 0.62; for atypical nevi, 0.53; and for BCC, 0.88. Both nurses and physicians overdiagnosed in the screening setting, the nurses more so than the physicians. Of the 128 persons screened who were advised to seek medical follow-up, 16 did not do so despite several reminders; their reasons are discussed. PMID- 2273110 TI - Neutrophilic eccrine hidradenitis in two neutropenic patients. AB - Neutrophilic eccrine hidradenitis is an uncommon, self-limited dermatosis with a variable clinical presentation. It seems to be due to chemotherapeutic drugs in most cases. Necrosis of the eccrine gland associated with a neutrophilic infiltrate is the histologic hallmark of this disease. We report two additional cases in neutropenic patients with acute myelogenous leukemia in which there was a striking lack of neutrophil infiltration. A new term, drug-associated eccrine hidradenitis, is suggested. PMID- 2273111 TI - The risk of developing subsequent nonmelanoma skin cancers. AB - Data from the Southeast Arizona Skin Cancer Registry collected during 1985 through June 1988 were used in this study. Patients who had a nonmelanoma skin cancer (basal cell or squamous cell carcinoma) removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until June 30, 1988. Twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second, third, and fourth nonmelanoma skin cancers. Analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year (36.39%), the rate of developing another nonmelanoma skin cancer depended on type (squamous cell carcinoma, 100%; basal cell carcinoma, 44.23% to 83.65%), and total risk decreased during the 1277 days of the study. PMID- 2273112 TI - Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms. AB - This study attempts to define histologic patterns in 1039 consecutive cases of basal cell carcinoma and to correlate these patterns with adequacy of margins of surgical excision. Five major histologic patterns were identified: nodular, 218 cases (21%); superficial, 181 cases (17%); micronodular, 151 cases (15%); infiltrative, 77 cases (7%); and morpheic, 11 cases (1%). A mixed pattern (two or more major histologic patterns) was present in 401 cases (38.5%). Our study indicates that nodular and superficial basal cell carcinomas can be completely removed by simple surgical excision in a high percentage of cases (93.6% and 96.4%, respectively) whereas the micronodular, infiltrative, and morpheic basal cell carcinomas have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision. Mixed patterns that consisted of combinations of the nodular, micronodular, or infiltrative types exhibited a behavior similar to the pattern that resulted in a greater chance of incomplete surgical removal. PMID- 2273113 TI - Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. AB - Pathologic hoof changes in horses and swine can be normalized by administration of biotin. This vitamin has been given orally to women with brittle fingernails or onychoschizia. The aim of the study was to test whether the favorable clinical results could be corroborated by scanning electron microscopy. We investigated the distal ends of the fingernails from 32 persons. They were placed into three groups: group A consisted of 10 control subjects with normal nails, group B comprised eight patients with brittle nails studied before and after biotin treatment, and group C was 14 patients with brittle nails in whom the administration of biotin did not coincide exactly with the initial and terminal clipping of the nails. The thickness of the nails in group B increased significantly by 25%. In group C, the increase was 7%. Splitting of the nails were reduced in groups B and C and the irregular cellular arrangement of the dorsal surface of brittle nails became more regular in all nails of group B and in 8 of 11 nails of group C. PMID- 2273114 TI - Scabies in nursing homes: an eradication program with permethrin 5% cream. AB - Permethrin 5% cream was used to treat scabies in three large nursing homes under a compassionate-plea protocol for chronic, therapy-resistant infestations. All residents, staff, and frequent visitors were treated whether or not symptomatic. Family members of these groups were treated either when symptomatic or directly exposed to scabies. Nine hundred ninety-five persons were treated, 202 of whom were diagnosed with scabies. Approximately 35% (111 of 313) of nursing home residents were diagnosed with scabies. These were patients in whom multiple treatments with other scabicides were unsuccessful. At the completion of the study, 195 patients were examined for efficacy of treatment. Of these, 91 (46.7%) had clearing of lesions with one medication application, 77 (39.5%) with two treatments, and 23 (11.8%) with three or more treatments. The overall cure rate was 98%. Adverse experiences occurred in 2.4% of cases and were mild (i.e., pruritus and rash). PMID- 2273115 TI - Lymphocytic infiltrates of the skin in association with cyclosporine therapy. AB - Three patients, one of whom has been previously reported, had erythematous papules and nodules of the face and upper part of the chest during cyclosporine therapy for inflammatory skin diseases. Histologic examination and DNA analysis (performed in two cases) revealed benign dermal lymphocytic infiltrates. In two cases proliferation of only T cells occurred. In the third case, both T and B cell populations were expanded and there was vacuolar degeneration of the basal layer of the epidermis and IgG, IgM, and C3 deposition along the dermoepidermal junction. These findings may be the result of cyclosporine-induced immune dysregulation. The lesions resolved in all patients after therapy was stopped. PMID- 2273116 TI - Treatment of port-wine stains during childhood with the flashlamp-pumped pulsed dye laser. AB - Seventy-three patients between the ages of 3 months to 14 years (average age 6 years 2 months) with port-wine stains were treated with the flashlamp-pumped pulsed dye laser. More than 75% lightening was achieved with an average of 2.5 treatments in 33 patients (45%), 50% to 74% lightening after an average of 1.7 treatments in 31 (42%), 26% to 49% lightening after 2 treatments in 5 (7%), and less than 25% lightening after 1 treatment in 4 (5%). The overall average lightening after one treatment was 53%. The percentage of lightening increased as the number of treatments increased. Three patients had 100% clearance of the port wine stain. Patients aged between 3 months and 6 years (44 patients) had a better response after the first treatment (55% lightening) than did patients aged between 7 and 14 years (29 patients with a 48% lightening; p = 0.027). Complications included cutaneous depressions in four patients, hyperpigmentation in 16 patients, and hypopigmentation in three patients. All complications were transient and disappeared completely. PMID- 2273118 TI - Congenital immunodeficiency syndromes with cutaneous manifestations. I. PMID- 2273117 TI - Microbiologic counts during outpatient office-based cutaneous surgery. AB - This study used microbiologic counts to evaluate bacterial contamination during cutaneous surgeries of the head and neck. Aerobic bacterial counts of the surgical field in cases with immediate closure (group A, n = 10 patients) and prolonged procedures such as Mohs micrographic surgery (group B, n = 15 patients) were performed three times during the operation. Cultures were taken before antiseptic application, 30 seconds after application, and before closure. Each group showed a statistically significant reduction in aerobic bacteria both 30 seconds after antiseptic application and before closure. All aerobic bacterial counts at both intervals were less than 100,000 colony-forming units/cm2 in each group. The consistent reduction in aerobic bacteria suggests that a clean technique for the two classes of office operating room surgeries provides low risk conditions for infection in relatively healthy patients. PMID- 2273120 TI - Adolph Rostenberg, Jr. PMID- 2273119 TI - Terminology in surface microscopy. Consensus meeting of the Committee on Analytical Morphology of the Arbeitsgemeinschaft Dermatologische Forschung, Hamburg, Federal Republic of Germany, Nov. 17, 1989. PMID- 2273121 TI - Unilateral colloid milium. PMID- 2273122 TI - Cisplatin chemotherapy for basal cell carcinoma: the need for posttreatment biopsy--report of a case. PMID- 2273123 TI - Lichen planus-like eruption with esophageal involvement as a result of cyanamide. PMID- 2273124 TI - Vesicular cutaneous T cell lymphoma presenting with gangrene. PMID- 2273125 TI - Sweet's syndrome associated with polycythemia rubra vera. PMID- 2273126 TI - Corticosteroid-sparing effect of hydroxychloroquine in a patient with early-onset Weber-Christian syndrome. PMID- 2273127 TI - Acrodermatitis enteropathica with giant squamous cell carcinomas. PMID- 2273128 TI - Successful treatment of acrodermatitis continua of Hallopeau with etretinate. PMID- 2273129 TI - Cutaneous leishmaniasis--chiclero ulcer in a Wisconsin native. PMID- 2273130 TI - Treatment of disseminated Mycobacterium chelonae infection with ciprofloxacin. PMID- 2273131 TI - Dual publication and manipulation of the editorial process. PMID- 2273132 TI - Multiple pigmented terminal hair cysts. PMID- 2273133 TI - Cyclosporine in dermatology. PMID- 2273134 TI - Effectiveness of penicillin G benzathine therapy for primary and secondary syphilis in HIV infection. PMID- 2273135 TI - Melkersson-Rosenthal syndrome and arthritis. PMID- 2273136 TI - Similar high frequency of IgA antireticulin and antiendomysial antibodies in dermatitis herpetiformis. PMID- 2273137 TI - Factors controlling histamine production in Swiss cheese inoculated with Lactobacillus buchneri. AB - Swiss cheese was made from raw milk inoculated with various concentrations of a histamine-producing strain of Lactobacillus buchneri. Histamine production in these cheeses was proportional to the initial number of L. buchneri present in the raw milk. The highest inoculum level tested was 10(5) L. buchneri/ml. This cheese contained 80 mg of histamine/100 g of cheese after 90 d of storage. Only 15 mg of histamine/100 g of cheese were detected after 90 d at the lowest inoculum level, 10(2) L. buchneri/ml. No histamine was detected in any of the Swiss cheese samples until after the brining stage. Perceptible growth of L. buchneri also did not occur until after the warm room treatment. Therefore, control of histamine formation in Swiss cheese requires control of the number of histamine-producing bacteria in the raw milk. A 5.5% NaCl concentration in DeMan, Rogosa, Sharpe (MRS) broth inhibited the production of histamine by L. buchneri, but the concentrations of NaCl typically found in Swiss cheese were not inhibitory. The histamine-producing isolate of L. buchneri survived heating at 49 to 80 degrees C for 10 min, suggesting that this organism would easily survive the normal heating process applied to raw milk used prior to making Swiss cheese. PMID- 2273138 TI - Nutrient profiles of commercial goat milk cheeses manufactured in the United States. AB - Thirty varieties of commercial goat milk cheeses collected from 13 manufacturers in 11 states of the US were evaluated. Concentration profiles of basic nutrients, major and trace minerals, their correlations, and mineral ratios in the caprine cheeses were determined to compare nutritional parameters among the varieties. Mean percentage of moisture, fat, protein, and ash for plain soft, semi-soft, hard, pepper, garlic, and herb cheeses were 59.8, 22.5, 18.9, 1.74; 43.2, 28.5, 26.2, 2.83; 27.4, 32.3, 25.4, 3.58; 57.3, 22.9, 21.6, 1.32; 64.3, 18.3, 16.7, 1.34; 59.1, 21.8, 17.3, 1.60, respectively. Ranges of mean concentrations (mg/100 g wet basis) of S, P, K, Mg, Ca, Na, Cl, Fe, Al, Mn, Cu, and Zn were: 2.00 to 8.05; 192 to 785; 7.03 to 103; 10.3 to 78.0; 57.1 to 1035; 225 to 924; 96.0 to 1260; .52 to 8.73; .47 to 22.1; .08 to .40; .44 to 1.32; .49 to 4.13, respectively. Twenty of the 30 varieties were very high or high moisture cheeses, which would suggest slow coagulation as the major mode of fabrication. Wide variations in the concentrations of P, K, Ca, Na, Cl, Fe, Al, and Zn were found among and within varieties of the cheeses. High concentrations and variations in Fe and Al in the cheeses indicate a significant possibility of uptake of these elements into the products during farmstead manufacturing processes. Percentage of moisture was negatively and significantly (P less than .05 or P less than .01) correlated with the concentrations of ash, fat, protein, and most of the minerals. Percentage of ash was positively and significantly correlated with the concentrations of macrominerals but negatively and less correlated with concentrations of Fe, Al, Mn, and Cu. The Na:K ratio was the highest of the five mineral ratios. Differences were significant for Ca:P, Ca:Mg, and Na:K ratios among the six types of goat cheese tested. PMID- 2273139 TI - Thymidine incorporation by lactating mammary epithelium during compensatory mammary growth in beef cattle. AB - Ten Hereford cows, 100 d into first lactation, were assigned to treatment or control groups to study compensatory growth of mammary glands. The right udder half of treatment cows was covered to prevent suckling by the calf, whereas control cows were suckled on all quarters. Milk production was estimated the day treatment began and 4 d later by machine milking following removal of calves for 12 h and i.v. injection of oxytocin. Five to 7 d after beginning treatment, cows were killed and mammary tissue was obtained from three regions within left and right glands for in vitro incubation with [3H]thymidine. Deoxyribonucleic acid of lactating udder halves did not increase in response to treatment although RNA: DNA ratio and milk production tended to increase. Incorporation of [3H]thymidine was greater in lactating quarters of treated cows than control cows (35,000 vs. 19,000 cpm/mg of DNA) with greatest incorporation in the basal regions of each gland. Furthermore, greatest incorporation of [3H]thymidine occurred in non suckled glands. Autoradiographic analyses confirmed incorporation data and indicated that 81% of proliferating cells were epithelial. Data suggest that proliferation of mammary epithelial cells, within both the lactating and nonlactating glands, occurred in response to milk stasis. PMID- 2273140 TI - Plasma somatotropin and prolactin concentrations in young dairy sires before and after a 24-hour fast. AB - To examine the efficacy of plasma concentrations of bST or prolactin as predictors of expected daughter performance, blood samples were collected from young Holstein sires. Blood samples were collected at 15-min intervals via jugular cannulas from 1000 until 1600 h (d 1), beginning 4 h after morning hay feeding. Bulls were not fed again until after collection of blood samples on d 2. Samples were collected at 15-min intervals from 1000 until 1300 h on d 2. Peak values and frequency of hormonal secretory patterns of each bull were characterized by an iterative process in which values greater than 2 SD from the mean were flagged as peaks and excluded from the subsequent calculation of SD and mean. The process continued until an iteration in which no new peaks were flagged. Imposition of a 24-h fast did not alter mean basal bST or prolactin concentrations, but reduced mean peak and overall concentrations of both hormones. The number of bST peaks on d 1 was inversely related to both USDA and Northeast Artificial Insemination Sire Comparison Pedigree Index for milk yield and both USDA and Northeast Artificial Insemination Sire Comparison sire PD for milk yield, but was positively correlated on d 2 with USDA Pedigree Index for milk yield. Mean peak bST on d 2 was correlated with Northeast Artificial Insemination Sire Comparison Estimated Breeding Value for fat yield and sire USDA PD for fat yield. Prolactin peak frequency on d 1 was negatively related to Northeast Artificial Insemination Sire Comparison Pedigree Index for milk yield and sire PD for fat yield. Difference between mean prolactin on d 1 and 2 was negatively related to Northeast Artificial Insemination Sire Comparison Pedigree Index for milk yield and Estimated Breeding Value for fat yield. Endocrine parameters in young sires may be related to genetic merit for production parameters. PMID- 2273141 TI - Validation and application of an assay for deoxyribonucleic acid to estimate concentrations of bull sperm. AB - Spectrophotometers are used for estimating sperm concentrations from raw ejaculates in semen processing laboratories. Unfortunately, these instruments have a limited detection spectrum and do not permit accurate quantification of sperm numbers in highly diluted or concentrated samples. The objectives of this study were to validate a DNA assay for quantification of sperm numbers in extended or undiluted semen samples and to determine precision of the assay. The principle of the assay is based upon a fluorescent dye that binds to adenine thymine base pairs in double-stranded DNA. Semen samples and calf thymus DNA standards were sonicated in 2 M NaCl buffer with 1 mM EDTA. The DNA content of samples was compared to standards of calf thymus DNA using fluorometry. Sensitivity of the assay was determined to be 1.4 x 10(5) sperm cells. Concentrations of sperm estimated from DNA assay values did not differ from flow cytometric cell counts. Assays were performed in three different laboratories, using different equipment, to assess the assay's repeatability. Estimates of sperm concentrations determined by the DNA assay were similar, regardless of location and source of equipment used to perform the assays. This assay fulfills statistical criteria for being sensitive, accurate, and repeatable, and it can be employed in laboratories processing semen for artificial insemination as a tool for spectrophotometer calibration, a check for straw filling accuracy, or to quantify sperm numbers in extended, packaged semen. PMID- 2273142 TI - Hemagglutination and hemolysis by Escherichia coli isolated from bovine intramammary infections. AB - Seventy-six Escherichia coli isolated from bovine intramammary infections were tested for hemagglutination and hemolysis of erythrocytes. Fifty-seven percent of isolates were hemagglutination-positive for bovine erythrocytes compared with 46% that agglutinated guinea pig erythrocytes. Twenty-eight percent of isolates were hemagglutination-positive for erythrocytes from both species. Only 14.5 and 2.6% of isolates were mannose-resistant, hemagglutination-positive for bovine and guinea pig erythrocytes, respectively. Neither duration nor severity of infection from which isolates were obtained differed between isolates that were hemagglutination-positive and hemagglutination-negative. Percentage distribution of hemagglutination-positive isolates did not differ among isolates from infections that originated at calving, during lactation, or the first half of the dry period. Hemagglutination reactions were also not related to in vitro growth in cell-free dry cow secretion. Percent of isolates that caused hemolysis of washed bovine erythrocytes was 2.6% compared to 3.9% for sheep erythrocytes. Hemolysis was not related to hemagglutination. Hemagglutination and hemolysis of erythrocytes did not appear to be virulence factors for E. coli isolated from bovine intramammary infections. PMID- 2273143 TI - Relationship of changes in condition score to cow health in Holsteins. AB - The relationship of body condition score with disease occurrence was examined in 561 cows in nine herds. Cows were body condition scored on a five-point scale (1 = thin, 5 = obese) every 2 wk from drying off until 150 d in milk. Cows scored between 3- and 3+ were considered to be in average or good condition. Cows scored less than or equal to 2+ were considered to be underconditioned, whereas those scored greater than or equal to 4- were considered to be overconditioned. Relationships of health and condition score were examined using multiple logistic regression for dichotomous outcomes (e.g., diseased or healthy). Cows that developed dystocia or were culled lost more condition during the dry period than those that did not develop dystocia or were not culled. Cows overconditioned at drying off were more likely to develop cystic ovarian disease and reproductive problems. Cows underconditioned or overconditioned at drying off were more prone to foot problems after calving. Cows overconditioned at 30 d postpartum were more likely to have metritis. PMID- 2273144 TI - Prediction of body composition in Holstein steers using urea space. AB - Our objective was to evaluate urea space estimate of body composition in Holstein steers by examining prediction equations based on chemical composition and by comparison of these equations to those developed for beef steers. Urea space was determined in 38 Holstein steers ranging in full-fed live weight from 143 to 404 kg by the change in plasma urea N concentration before and 12 min after the midpoint of an intravenous infusion of 130 mg urea/kg live weight (20% solution in .9% saline). The relationship between empty body water (mean, 159.9 kg) and urea space in Holstein steers (Sy.x = 7.9 kg, R2 = .95) showed slope (.93) and intercept (20.6) similar to those of beef steers (.92 and 21.8). Predictions of empty body water, fat, and protein were slightly improved by including urea space in multiple regression equations with full-fed live weight over equations based on full-fed live weight alone. Predicted mean body protein in Holstein steers based on previous equations developed with beef steers was not different from chemically determined empty body protein. Beef steer equations underestimated mean empty body water (155.4 vs. 159.9 kg) and overestimated mean empty body fat (29.8 vs. 25.8 kg). These data suggest that urea space can be used to improve predictions of body composition on a mass basis in Holstein steers over that using of live weight measurements alone and that prediction equations may be different for different types of cattle. PMID- 2273146 TI - Effect of particle size of forage and rumen cannulation upon chewing activity and laterality in dairy cows. AB - Three ruminally cannulated Holstein dairy cows housed in free stalls (with .7% slope) were fed three total mixed rations, differing in silage particle size, in a 3 x 3 Latin square design. Observations on cow behavior were made every 5 min during 24 h for each of three periods. Additional observations of six cows (three intact, three cannulated) housed under identical conditions yielded information concerning recumbent rumination activity and laterality. Results indicated that decreasing particle size of forage reduced time spent ruminating, whether standing or recumbent, and had no effect upon rumination rate or number of rumination bouts per 24-h period. Eating time was unaffected by treatment. Effect of forage particle size upon baseline rumination activity appeared to be most pronounced from 0800 to 2000 h, although maximum rumination activity occurred during nighttime hours. Ruminally cannulated cows demonstrated increased right side laterality (70%) compared with intact cows (47%), but the cows tend to ruminate while lying on their left side. The percentage of time spent ruminating while recumbent on the left side was similar (55%) for intact and cannulated cows. PMID- 2273145 TI - Evaluation of a duodenal cannula for dairy cattle. AB - Two dairy cows fitted with rumen cannulas and closed T-shaped duodenal cannulas were utilized to examine duodenal cannula function and indigestible marker performance. Cows were fed one of two mixed diets and hay separately twice daily. Diets contained sources of supplemental protein that differed in expected rate of ruminal degradation. Duodenal DM flow was estimated with the indigestible markers, Cr-mordanted cell wall, Yb-soaked whole crop oat silage, and Co-EDTA. Duodenal DM flow using Co-EDTA was 49% higher than that estimated by reference to Cr-mordanted cell wall; Yb estimated an intermediate flow. Results are interpreted to suggest that the system developed to estimate duodenal digesta flow was not completely successful. However, qualitative assessment indicates that results are substantially better than those previously observed with simple gutter-type T-piece duodenal cannulas. Application of biological tests to the results suggests the failure of the system was not a result of cannula failure per se but due to the method of indigestible marker administration. Cows fed rumen-degraded proteins (slow versus rapid) had higher rumen nonammonia N pools, a trend for higher forestomach fiber fermentation, and a trend for lower forestomach digestion of N. These results are consistent with current knowledge of the influence of slowly degraded proteins on rumen fermentation. PMID- 2273147 TI - Effect of duration of supplementation of selenium and vitamin E on periparturient dairy cows. AB - Cows were fed diets either supplemented with .2 ppm Se and 70 IU vitamin E/kg diet DM (21 cows) or unsupplemented (40 cows) during the dry period (approximately 60 d). From parturition to 21 d of lactation, cows were fed diets that were either supplemented with .3 ppm Se and 40 IU/kg vitamin E or unsupplemented. At d 21 following parturition, 18 cows fed the unsupplemented diet were switched to diets containing 0 or .3 ppm supplemental Se and 0 or 40 IU/kg supplemental vitamin E arranged factorially. These diets were fed for the next 32 d. The remaining cows continued their respective diets for 32 d. Plasma Se concentrations averaged .1 microgram/ml for supplemented cows but were .05 micrograms/ml for unsupplemented cows. Plasma Se concentration from cows fed supplemental Se from 21 to 53 d postpartum increased rapidly and were not different from long-term supplemented cows. Whole blood glutathione peroxidase activity was lower in unsupplemented than in supplemented cows. Short-term Se supplementation increased glutathione peroxidase activity above that for unsupplemented animals, but activity was still less than that in long-term supplemented animals. Plasma alpha-tocopherol concentrations at parturition and d 21 postpartum were lower in unsupplemented than in supplemented animals. On d 53 postpartum, no differences in plasma alpha-tocopherol concentrations were found between long-term supplemented and unsupplemented cows. Supplementing vitamin E during the dry period increased alpha-tocopherol content of colostrum. PMID- 2273148 TI - Decreased plasma retinol, alpha-tocopherol, and zinc concentration during the periparturient period: effect of milk fever. AB - Retinol (vitamin A), alpha-tocopherol (vitamin E), and Zn are micronutrients essential for health and performance. We determined the effects of parturition, lactation, and periparturient Ca status on plasma retinol, alpha-tocopherol, and Zn in 18 Jersey cows during the 2 wk before and after parturition. Six cows developed clinical milk fever. Prepartum plasma concentrations of retinol, alpha tocopherol, and Zn decreased progressively in all animals. A nadir was reached at 1 d postpartum when concentrations declined to 38, 47, and 67%, respectively, of prepartal baseline concentrations. Plasma Zn returned to baseline concentrations within 3 d of calving, and plasma alpha-tocopherol returned toward baseline about 10 d after calving. Plasma retinol remained below baseline concentrations throughout the first 2 wk of lactation. The decline in plasma Zn observed at calving was more severe in cows with milk fever (parturient paresis) than in cows without milk fever. The decrease in plasma retinol and alpha-tocopherol observed at parturition was similar in cows with or without milk fever. These data document an acute decline in plasma retinol, alpha-tocopherol, and Zn in the immediate periparturient period and indicate that the decline in plasma Zn is more severe in cows with milk fever. PMID- 2273149 TI - Influence of dietary protein sources on the amino acid profiles available for digestion and metabolism in lactating cows. AB - Six lactating Holstein cows, fitted with T-type cannulas in the proximal duodenum, were used in a replicated 3 x 3 Latin square design to determine influence of supplemental protein on amino acid profiles of duodenal chyme and plasma. Protein sources were blood meal, corn gluten meal, and cottonseed meal, which furnished approximately 46% of the total protein in corn-grain corn silage diets. Markers were 15N to estimate rumen bacteria and chromic oxide to estimate nutrient flow. Dry matter intake was lowest on blood meal. Duodenal flow of N exceeded N intake 23% on blood meal and corn gluten meal. Percentages of organic matter and protein digested in the rumen were 56.5, 41.8; 61.2, 53.4; and 50.6, 56.2 for the respective diets. Variation in patterns of amino acids flowing to the duodenum, but not in coccygeal blood, closely reflected dietary differences with six of eight essential amino acids highest for the same treatment in both diet and duodenal chyme. Essential amino acids in least abundance for milk production, measured by mammary extraction coefficients, differed among diets. We conclude that supplemental protein source influences greatly the quantity and pattern of amino acids available for digestion in lactating dairy cows. PMID- 2273150 TI - Effects of fish meal protein supplementation on milk yield and composition and blood constituents of dairy cows. AB - Ten holstein and 10 Ayrshire cows were fed diets containing undegradable intake protein from either fish meal or corn gluten meal. Cows were introduced to diets 10 d before projected calving date and individually fed blended rations until 60 d postpartum. Diets were balanced for NE1, CP, and degradable and undegradable protein. Source of undegradable protein did not affect total or FCM yields, DM intake, or milk protein percentage. Cows on fish meal diets tended to lose less BW than those on the corn gluten meal supplement (5.3 vs. 10.3% loss of initial BW). Fish meal supplementation resulted in decreased milk fat and SNF percentage (3.2 vs. 4.2% and 8.37 vs. 8.65%, respectively), but diet did not affect total milk fat, protein, or SNF yield. Plasma nonesterified fatty acids decreased and serum insulin increased with increasing weeks postpartum but were not affected by diet. In this study, no significant advantage was found to using fish meal as a source of undegradable intake protein and feed cost was higher when it was used. PMID- 2273151 TI - Use of recombinant bovine somatotropin for up to two consecutive lactations on dairy production traits. AB - Fifteen (control) cows were injected with saline; 28 cows were treated with rbST (15 with 10.3 and 13 with 20.6 mg/d). Fourteen of the 28 treated cows had between injected with rbST in the previous lactation. A total of 29 cows in the present trial had not received rbST in previous lactation. Treatment injections were started between wk 4 and 5 of lactation and continued for 266 consecutive days. Milk production, fee intake and efficiency, and BW data were recorded for 3 wk before and 3 wk after a 38-wk rbST treatment period. Administration of rbST increased average FCM yields in the current lactation by 19%, increased feed energy intake by 7%, and decreased feed conversion (energy intake per unit FCM output) by 17%. Previous treatment with rbST did not significantly affect current milk production but caused a nonsignificant increase in feed intake and a significant, unfavorable, increase in feed conversion of 12%. The results suggest that the advantages of rbST in terms of increased milk yield are maintained for a second consecutive lactation of rbST administration. However, the advantages of rbST in terms of improved feed conversion may be substantially reduced in a second consecutive lactation of administration. PMID- 2273152 TI - Health and reproductive performance of dairy cows treated for up to two consecutive lactations with bovine somatotropin. AB - Forty-three purebred Holstein cows were put on an rbST milk production trial. There were 15 control cows (saline-injected), 15 cows injected with 10.3 mg rbST/d and 13 cows injected with 20.6 mg rbST/d. Injections were initiated between wk 4 and 5 of lactation and continued for 266 consecutive days. Fourteen of the rbST-treated cows were treated with one of three dosages of rbST in the previous lactation (10.3, 20.6, or 41.2 rbST/d). The objective of this study was to determine the health and reproductive efficiency of cows treated with rbST for up to two consecutive lactations relative to control cows. The incidence of 11 health-related variables before, during, and after the 38-wk injection period were not different among treatment groups. Previous treatment with rbST had no effect on reproductive variables; however, there was evidence that injections with the highest dosage of rbST in the current lactation resulted in lowered reproductive efficiency. It is possible that the effects of rbST on early lactation energy and nitrogen balance have confounding effects on the estrous cycle. PMID- 2273153 TI - Effects of recombinant bovine somatotropin on nutritional status of dairy cows during pregnancy and of their calves. AB - Objectives of this trial were to evaluate effects of rbST on the nutritional status of 24 Holstein cows during pregnancy and of their calves from birth to weaning. All cows conceived during injection with either a placebo or 350 mg of rbST in a sustained-release vehicle every 14 d commencing 98 to 112 d postpartum for their entire lactation. In Experiment 1, blood samples were collected at 90, 180, and 270 d postconception in cows. Concentrations of urea, glucose, albumin, total proteins, Ca, P, insulin, cortisol, hemoglobin, and hematocrit were unaffected by treatment as well as BW, body condition scores, and energy balances at conception and during pregnancy. Days open and calving interval were not significantly different but were numerically increased by 31 d in rbST-injected cows. Nonesterified fatty acids, bST, and insulin-like growth factor-I in plasma were elevated significantly in rbST-injected cows. In Experiment 2, blood samples were collected at birth and at 1, 3, 5, and 7 wk in calves born from cows of Experiment 1. Circulating concentrations of glucose, nonesterified fatty acids, albumin, total proteins, hemoglobin, insulin, cortisol, bST, insulin-like growth factor-I, and hematocrit, blood pH, blood gases and buffer capacity, birth weight and rate of weight gain, height at withers, and heart girth from birth to weaning were not different due to treatment of dam. However, some parameters were significantly different based on age and sex. These data support previous assumptions that the magnitude of the modifications in nutrient partitioning produced by rbST do not affect the hierarchy of the partitioning process for the calf. PMID- 2273154 TI - Effects of recombinant bovine somatotropin on nutritional status and liver function of lactating dairy cows. AB - Twenty-four high producing, multiparous Holstein cows were utilized to evaluate effects of long-term administration of sustained-release rbST on blood pH, gases, buffer capacity, circulating metabolites and hormones, and on liver lipid content and functions during lactation. Treatment, commencing 98 to 112 d postpartum and continued until d 305, consisted of a subcutaneous injection of a placebo or 350 mg of rbST every 14 d. Milk and 3.5% FCM were increased significantly by rbST, but milk fat and protein content, feed intake, energy balance, corrected feed efficiency for milk production, and body condition scores were unaffected. Somatotropin decreased blood pH and buffer capacity by decreasing bicarbonate without affecting blood partial pressures of oxygen or carbon dioxide. Concentration of plasma albumin was decreased and nonesterified fatty acids, glucose, insulin, rbST and insulin-like growth factor-I were increased by treatment. Total plasma proteins and cortisol, hemoglobin, and hematocrit were unaffected. Liver DM, total lipid and triacylglycerol contents, and plasma 3 hydroxybutyrate and glutamic oxalacetic transaminase were not affected by rbST, but the percentage of triacylglycerol in total lipids was increased. Results of this experiment suggest that rbST exhibited lipolytic and diabetogenic activities in lactating dairy cows in vivo and that these effects might be important for the increase in nutrient partitioning toward the mammary gland elicited by rbST. PMID- 2273155 TI - Effect of curd forming of colostrum on absorption of immunoglobulin G in newborn calves. AB - Pooled colostrum from the first three milkings postpartum was used in two trials to determine the effect of abomasal curd forming on absorption of IgG in newborn calves. In Experiment 1, two groups of seven Friesland calves each received 1 h postpartum 1 L of untreated colostrum or colostrum treated with an oxalic acid sodium hydroxide buffer to prevent coagulation. Calves were not allowed to suckle their dams and received colostrum in teat bottles. The same treatments were applied for Experiment 2, except that eight calves per group were used, and each calf received 2 L colostrum. Blood samples were taken from the jugular vein 6 h postfeeding, and plasma IgG concentration was determined by a radial immunodiffusion technique. Plasma IgG concentration, estimated IgG absorption, and apparent efficiency of absorption 6 h postfeeding for the coagulable and noncoagulable treatments, respectively, were 11.6 and 6.6 mg/ml, 28.1 and 15.8 g/d, and 87.8 and 49.3% for Experiment 1; and 21.2 and 12.9 mg/ml, 48.6 and 34.2 g/d, and 60.8 and 42.8% for Experiment 2. It was concluded that the curd-forming ability of colostrum is an important factor in effective absorption of IgG by calves during the first 6 h postfeeding. PMID- 2273156 TI - Metabolism of vitamin K and influence on prothrombin time in milk-fed preruminant calves. AB - The metabolism of vitamin K was studied in 66 preruminant veal calves that were fed supplemental menadione sodium bisulfite complex or phylloquinone. Menadione sodium bisulfite complex was converted by intestinal microorganisms to menaquinone-4 and absorbed and stored in the liver as menaquinone-4. Phylloquinone was absorbed unchanged. Production of menaquinones 6, 7, 8, and 10 by intestinal microorganisms also was observed, but was not dependent upon dietary vitamin K. No difference was noted in prothrombin time among the groups. Intestinal microorganisms provide sufficient vitamin K to meet the physiological needs of calves fed milk replacers. Menaquinone-4 was the form of vitamin K used to meet the calf's requirement. PMID- 2273157 TI - Parentage identification in the bovine using "deoxyribonucleic acid fingerprints". PMID- 2273158 TI - Economics of mastitis control. AB - The frequency of use and the effects of mastitis control practices on SCC and milk yield were investigated. A survey of current management practices was combined with DHI production information to determine the relationship between milk yield, SCC, management practices, and production and producer characteristics under field conditions. The expected negative relationship between SCC and milk, fat, and protein yield was substantiated. The SCC for an individual cow was a better indicator of milk loss than was a bulk tank SCC. Most recommended mastitis control practices were estimated to be economically beneficial; however, using a sanitizer in the washing solution and having a company change the milking machine inflations were not economical. Questions were raised about the economic efficiency and efficacy of treating all cows as opposed to selected cows at drying off. PMID- 2273159 TI - Dohi memorial lecture. Laser medicine and laser dermatology. AB - As laser devices become smaller, more reliable, and less expensive, dermatology will benefit from new laser-based therapeutic and diagnostic methods. Already there are simple, non-scarring, and relatively painless techniques for removal of pigmented lesions, tattoos, and vascular lesions. Because much of the basic and applied research in photobiology is grounded in dermatology research, dermatology will continue to be a major contributor to advances in laser medicine and photomedicine. An increase in understanding and ability to manipulate laser tissue interactions will add greatly to the future of medicine and surgery, especially in applications utilizing pulsed lasers. We are learning how to: 1) vary wavelength, pulse duration, and energy to influence the nature of microscopic injury and host response in order to achieve a net therapeutic benefit; 2) utilize exogenous chromophores to increase the selection of targets for laser radiation; and 3) capture optical technology developed for industrial and military use, in order to benefit mankind with new medical and surgical techniques. PMID- 2273160 TI - Photoprotective effect of topically applied superoxide dismutase on sunburn reaction in comparison with sunscreen. AB - Photoprotective effect of topically applied superoxide dismutase (SOD) to guinea pig skin was compared with a commercially available sunscreen agent after a single exposure to UVB. While cutaneous SOD activity was remarkably decrease in non-treated control animals, both topical SOD and sunscreen agent significantly reduced the decrease in skin SOD activity after UVB irradiation. However, only the sunscreen agent successfully reduced erythema reaction 24h after irradiation but topical SOD failed. These findings suggest that topical SOD protects skin from photo-oxidative damage without affecting erythema response, and thus, from a practical standpoint, sunscreen agents, when compared with topical antioxidants, seem better at present for daily photoprotection. PMID- 2273162 TI - Cutaneous involvement as a presenting feature of monocytic leukemia: morphological and immunohistochemical studies. AB - The clinical and pathological findings in a patient with monocytic aleukemic leukemia presenting initially as multiple monoblastic tumors of the skin is described. The patient was a 35-year-old Japanese woman, who had first noticed multiple, asymptomatic, reddish-brown papules on her trunk. Asymptomatic enlargements of several lymph nodes were present in the bilateral cervical and axillary areas. There was no hepatosplenomegaly, sternal tenderness, bruising, or bleeding. The skin and lymph node biopsies were originally interpreted as malignant lymphoma. The diagnosis of acute monocytic leukemia was established when bone marrow involvement was detected. Immunohistochemical observation of the skin eruptions revealed the following: Positive staining with lysozyme was noted in almost half of the infiltrating atypical cells. Most of the infiltrating cells reacted positively with antisera to Leu-M5 and some of them reacted to Leu-M1. The helper T cell antibody, Leu-3a+3b, showed weak positive staining of most infiltrating cells. However, there were no reactions with antisera to Leu-6, Leu 7, Leu-14, CALLA, OKT 6, OKT 8, OKT 16, OKB 19, OKM 14, beta F1, or delta TCS1. OKM 5-positive keratinocytes were observed in some parts of the upper epidermis, although no OKM 5 expression could be detected on any tumor cells. Cytochemistry, immunohistochemistry, and electron microscopy can aid in the diagnosis of monocytic leukemia. This case illustrates the importance of using an expanded panel of monoclonal antisera in certain hematopoietic tumors. PMID- 2273161 TI - A possible pathogenesis for Blackfoot disease--effects of trivalent arsenic (As2O3) on cultured human umbilical vein endothelial cells. AB - Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease found among the inhabitants of the southwest coast of Taiwan. The clinical features of BFD are similar to those of Buerger's disease. Pathology shows arteriosclerosis obliterans and thromboangiitis obliterans. The high arsenic content of artesian well water in the area is regarded as the main causal factor of this disease. Therefore, the purpose of this study was to observe the toxic effects of various arsenic concentrations on cultured human umbilical vein endothelial cells (HUV EC). The methods of this study included cell growth assay, 51Cr-release assay, and staining of Factor VIII related antigen (FVIII-RAg) and Ulex europaeus agglutinin I (UEA-I) binding sites of HUV-EC. The following data were obtained: 1) no obvious cytotoxicity in 51Cr-release assay; 2) inhibition of the synthesis of both FVIII-RAg and UEA-I binding sites when the arsenic concentration was above 100 ng/ml; 3) dose-dependent inhibition of growth of HUV-EC by any concentration of arsenic. At a higher concentration of more than 100 ng/ml, arsenic inhibited endothelial cell proliferation and glycoprotein synthesis, whereas it only inhibited the proliferation at a lower concentration of less than 50 ng/ml. It is suggested that arsenic, at both higher and lower concentrations, may damage endothelial cells. Such damage may play an important role in the pathogenesis of BFD. PMID- 2273163 TI - Clinical survey of syphilis at the Dermatological Clinic of Nippon Medical School Hospital from 1984 to 1988, with special reference to the recent clinical manifestations and evaluation of IgM antibodies to Treponema pallidum. AB - One hundred eighty-one patients with syphilis were seen from May 1, 1984, to April 30, 1988 at the Dermatological Clinic of Nippon Medical School Hospital. The incidence of syphilis has increased gradually year by year. The number of early infectious syphilis cases was almost twice as high as late latent syphilis ones. As a source of infection, female prostitutes were noteworthy. Among primary syphilis cases, multiple chancres were observed in 29.2%. The frequency of ulcus durum was much higher than initial sclerosis. A relationship with oral sex is suggested. Among secondary syphilis cases, pruritus was observed in 23.9%, prominently on volar lesions. Psoriasiform papular and macular syphilide were the commonest features. Secondary syphilis with persisting chancres were seen in 41.3% and is gradually increasing. JH reactions were observed in 26.3%. The frequency was highest in late primary and in early secondary stages. IgM-TPHA and IgG-TPHA were tested in 94 sera by gel-filtration and 77 by HPLC. IgM-TPHA tests were reactive in virtually all the sera from untreated syphilis cases. The titres in untreated syphilis were higher than in treated cases. IgM-TPHA/IgM-TPHA + IgG TPHA was higher in early syphilis than in late syphilis. Fifty-eight untreated cases were tested at frequent intervals after treatment for up to 12 months. IgM antibodies disappeared in 53 patients within 12 months. Non-treponemal antibodies measured by the CF test disappeared within 15 patients and TPHA tests remained positive after 12 months in all patients. IgM-TPHA may support a diagnosis of active syphilis. PMID- 2273164 TI - Laboratory observations of Haemaphysalis longicornis Neumann after a human bite. AB - A case of a tick bite with Haemaphysalis longicornis Neumann is reported. The tick was found on the left lower abdomen of a 62-year-old female. The tick bite occurred in Fuchu city, a suburb of Tokyo. This paper presents laboratory observations of the process of Haemaphysalis longicornis Neumann laying eggs and becoming larvae after biting a human. The results of our observations include the size of female adult (length: 7.5 mm, width: 5.2 mm, weight: 96 mg) after blood sucking, preoviposition period (7 days), oviposition period (24 days), number of eggs (760 eggs), egg size (length: 0.58-0.62 mm, width: 0.39-0.42 mm), size of unfed larva (length: 0.45-0.5 mm, width: 0.45-0.5 mm) and unfed larva period until death, which ranged from 10 days to 62 days. PMID- 2273165 TI - Linear IgA dermatosis and Hodgkin's lymphoma--report of a case in an African and review of the literature. AB - Linear IgA dermatosis and Hodgkin's lymphoma were diagnosed at the same time in a 47-year-old Black South African man. Skin changes of linear IgA dermatosis responded to a combined treatment with dapsone and MOPP regimen. Prior administration of dapsone alone did not result in improvement of the skin condition. Four documented cases of linear IgA dermatosis and lymphoma outside the gastrointestinal tract, three of them of Hodgkin's type, have been reported in the literature. Review of the literature suggests that different forms of lymphoma seem to be associated with linear IgA dermatosis and dermatitis herpetiformis. The present patient represents the first immunologically verified case of linear IgA dermatosis in an adult Black African. PMID- 2273166 TI - Unilateral dermatomal superficial telangiectasia. AB - A three-year-old boy with unilateral dermatomal superficial telangiectasia (UDST) is the first reported case with skin lesions in two non-adjacent areas (dermatomal areas of Trigeminal2 and L4-5). In this case, onset occurred at an early age, the onset was eight months after an operation, and the liver function was normal; therefore we believe it is congenital, even though the patient had undergone an extensive right hepatectomy to remove a hamartoma in his liver at the age of four months. PMID- 2273167 TI - Basal cell carcinoma originating from an epidermoid cyst. AB - Basal cell carcinoma (BCC) originating from an epidermoid cyst which existed for about 50 years was seen in a 78-year-old Japanese male. Nests of basal cell carcinoma were connected with the epidermoid cyst, partially replacing the cyst wall. PMID- 2273168 TI - Unusual fatty acid in Sporothrix schenckii. AB - Sporothrix schenckii was isolated from a specimen from a 75-year-old woman with lymphatic sporotrichosis on the left forearm. A mass of fungi was cultured in liquid Sabouraud dextrose broth for three months. Crude lipids were extracted from the cultured fungal mass. Total fatty acids and free fatty acids were isolated, purified, and then analyzed using thin-layer chromatography, gas liquid chromatography, and mass spectrometry. Total fatty acid composition consisted of seven molecular species of C15:0 (2.5%), C16:1 (2.5%), C16:0 (64.5%), 2-Me-C16:0 (5.1%), C17:0 (2.0%), C18:1 (18.0%) and C18:0 (5.3%). Free fatty acid composition consisted of eight species of C14:0 (2.0%), C15:1 (4.1%), C16:1 (7.5%), C16:0 (68.5%), C17:0 (0.6%), C18:2 (2.0%), C18:1 (14.5%) and of C18:0 (0.9%). 2-Me C16:0 was detected in the fungus for the first time. PMID- 2273169 TI - [The ultrastructure of dark and light thrombocytes]. AB - Ultrastructure of thrombocytes with dark, light and intermediate hyaloplasm density has been studied in a population of thrombocytes of human peripheral blood. Excretion of specific granules, development of vacuolar structure, the increase in contact activity, and the cytochemical activity of phosphohydrolythic enzymes is accompanied by the corresponding decrease in the hyaloplasm density. Dark thrombocytes may be considered as potentially active ones, and the light ones, as actively functioning thrombocytes. PMID- 2273170 TI - [An analysis of the action of metalloatranes on the hypothalamic neurons of rats]. AB - Neurophysiological effects of different metal derivatives of atranes at single and repeated introduction into rats have been studied. Spontaneous activity of separate hypothalamic neurons was found to change at introduction of atranes. Discharge activity of hypothalamic [correction of pretubercular] cells changed both in phasic and in tonic mode in response to single injection of atranes. The data obtained allow to conclude that metal derivatives of atranes do not exert specific effect on hypothalamic neurons. PMID- 2273172 TI - [The extracellular epidermal compartment of mammals]. AB - The structure and function of the intercorneocyte cement of the corneal layer of epidermis in mammals has been reviewed on the basis of the author's and published data. Two functions of the layer have been considered: a water-tight barrier and a desquamation. Chemical structure of the barrier has been characterized. Comparison of the barrier in water and terrestrial mammals suggest that the peculiarities of the barrier correlate with different pathways of keratinization. Factors that determine the adhesion have been described. The authors show the possibility to use natural models for studying the processes of keratinization and, in particular, functioning the intercellular compartment of the corneal layer. PMID- 2273171 TI - [The antagonism of the natural microflora of grain as a regulating factor in Fusarium sporotrichiella toxin formation]. AB - The ability of 32 fungi species of 9 genera that belong to field grain microflora to inhibit the growth of F. sporotrichiella strain 53315 producing T2 toxin has been studied. Antagonistic properties have been found in representatives of Epicoccum and Drechslera genera. Estimation of T2 toxin in grain by microbiological method and by thin layer chromatography yielded similar results. PMID- 2273173 TI - [The kinological identification of individual scents in the traces of the vital activities of 4 vertebrate species]. AB - One can successfully identify individual odors of almost any terrestrial vertebrates using laboratory dogs. The excretions can be collected on adsorbent paper and conserved for subsequent identification. It has been experimentally shown that the odor of house mice remains stable during the whole life span and that the stabilization of dog-identifiable odors finishes in young mice at 14 day. The method tested will allow to create individual banks of animal odors, e.g. for identification of rare species. PMID- 2273174 TI - [Regenerative myogenesis of the leg muscles during experimental lengthening]. AB - Regenerative myogenesis of an extremity regenerating by bilocal distraction osteosynthesis according to Ilizarov has been studied by light end electron microscopy. During the osteosynthesis, the action of the factor of mechanical tension is observed. Muscles elongate because myogenic cells incorporate into muscular fibers in the area of their attachment to dense connective tissues. The data obtained confirm the role of mechanical tension in spatial organization of cells, in morphogenetic and formation processes. PMID- 2273175 TI - [The resonance phenomenon in the human cardiorespiratory-hemodynamic system]. AB - The ratio of the period of cardiac cycle to the period of vessel autofluctuations is constant in healthy resting humans. This ratio constitutes 1.309 +/- 0.068. The same correlation is observed between the duration of the pneumo-cycle and the period of respiratory arrhythmia. At working and post-constriction hyperemia, there is a resonance in cardiac-respiratory-hemodynamic system that synchronizes the fluctuation processes of its constituent elements and increases the RVG amplitude. The data obtained have been discussed. PMID- 2273176 TI - [The effect of sugars on the activity of sorbitol dehydrogenase from the cytoplasm of bovine liver cells]. AB - The effect of sugar and its phosphate derivatives on sorbitoldehydrogenase from bovine liver has been studied. The presence of 100 mM glucose, mannose, and arabinose did not influence that activity of the studied reaction, whereas fructose, sorbose, and xylose, inhibit the reaction by 20-25%. This can be explained in terms of inhibition by the final reaction products. Inhibition by glucose-6-phosphate (24%), glucose-1-phosphate (21%), and fructose-6-phosphate (42%) is of particular interest since these compounds may play a regulatory role. PMID- 2273178 TI - [A model of the compression of acoustic information in neuronal networks]. AB - A model for processing of acoustic information in neuron networks has been proposed. The model takes into account the final rate of transfer of electric signal along the nerve fibers. The model indicates a possibility for the existence of a mechanism of compression of the input wide frequency band signal that retains its energetic parameters (in a certain limit). The model allowed to create a very efficient synthesizer of repellent acoustic signals that may be used to manage the bird behavior and regulate their numbers. PMID- 2273177 TI - [An immunohistochemical study of the primordium and primary differentiation of the parafollicular cells in the human thyroid]. AB - Formation and differentiation of calcitonin-secreting cells has been studied in human embryos. The cells form from the entodermal part of the rudiment of the last pharyngeal cavity. They do not secrete calcitonin before incorporation into the thyroid gland. The first calcitonin-secreting cells appear in the thyroid gland as a diffuse net. The properties and origin of this net have been described. PMID- 2273179 TI - [The pain sensitivity and behavioral reactivity of rats in somatic and visceral pain states]. AB - The vocalization thresholds and latent periods of motile reaction have been studied in normal rats, at extremity trauma, and at intraperitoneal injection of an algogen [correction of allogene]. The dissociation of changes in pain sensitivity and motile reactivity in during, visceral and somatic pain conditions was observed. A strong hypoalgesia during visceral stimulation and hyperalgesia at trauma accompanied by inhibition of motile activity have been discussed from the point of view of their significance in defense reactions of the organism at pain conditions of various nature. PMID- 2273181 TI - [Protein synthesis in a hepatocyte culture in the presence of exogenous adenylic and guanyl nucleotides]. AB - Circahoral opposite-in phase fluctuations of protein syntheses and intracellular ATP content have been observed in monolayer hepatocyte cell culture. Peculiarities of protein synthesis in hepatocytes have been studied in vitro in presence of adenylic and guanylic nucleotides. Addition of exogenous ATP leads to the decrease in the level of protein synthesis and smoothing off of the fluctuations. The presence of exogenous ADP leads to the increase in protein synthesis and retaining of the amplitude of fluctuations of this process. Effect of exogenous GTP is similar to that of ATP. Different aspects of action of exogenous NTPs on the rhythms of protein synthesis have been considered. PMID- 2273180 TI - [The copper-dependent accumulation of magnesium in Escherichia coli]. AB - Cu2(+)-induced accumulation of Mg ions by E. coli cells has been studied. The accumulation was demonstrated to take place only when the cell had endogenous energetic resources. The data obtained and their correlation with the data on Cu2+ binding by bacterial cells and Cu2(+)-dependent streptomycin accumulation allowed to conclude that copper induced nonspecific potential-dependent influx of cations into cells. PMID- 2273182 TI - [The reaction of microbial associations on separate areas of mammalian skin to a change in the physiologic state of the animals]. AB - Changes in the physiological state of mammal organism and stressor action cause the reaction of microbial associations on naked skin parts. The peculiarities of the reaction have been described. PMID- 2273183 TI - [The effect of the causative agent of tick-borne relapsing fever on the respiration of the vector Ornithodoros papillipes (Birula, 1895) (Ixodoidea, Argasidae)]. AB - A relatively low level of normal respiratory metabolism in O. papillipes has been observed as compared to most other invertebrates and even ixodid ticks. It is connected with biological peculiarities and habitat of this species. Changes in respiratory metabolism under the influence of Borrelia have been revealed. These changes vary at different stages of tick life cycle. In long-fasting infected individuals, respiration is further inhibited, and in nourished ones, is increased as compared to noninfected ticks. PMID- 2273184 TI - [Study of biological materials based on indentometry]. AB - The general multiparameter system of testing chemical compounds allows to study biological matter on the basis of purely physical approaches. A "Tissue-1" device allows to study all types of biological tissues able to withstand different kinds of passive and/or active mechanic load. PMID- 2273185 TI - [A zinc-binding non-metallothionein protein isolated from normal and regenerating liver]. AB - A zinc-binding nonmetallothionein protein has been isolated from cytosol of normal and regenerating liver. It is a dimer with molecular weight of ca. 20 kDa and contains one zinc ion. Zinc-dependent monomer in equilibrium dimer transition was observed. The role of the protein in regulation of intracellular content of zinc ions has been discussed. PMID- 2273186 TI - [Equation of state and life span of poikilothermic animals]. AB - An equation of state of a living organism that corresponds to the Kleiber's empirical dependence has been found using the conditions of entropy and energy balance. Life span of animals has been calculated using the equation obtained and it was found to depend inversely on metabolism intensity. PMID- 2273187 TI - [The role of oxygen in the inhibition of Escherichia coli respiration by copper ions]. AB - Effect of Cu2+ on E. coli respiration and the role of oxygen in toxic action of copper has been studied. Stimulation of respiration is observed at initial time after introduction of Cu2+. It is based on a nonspecific cell response to membrane damage. After finishing of transitory processes, Cu2+ influenced respiration by noncompetitive inhibition, i.e. copper-sensitive enzyme can be oxygenated or nonoxygenated, and only the latter form of the enzyme is inhibited. PMID- 2273188 TI - [Bacillus thuringiensis subsp. toguchini--a new subspecies of crystal-forming bacteria]. AB - A new subspecies of B. thuringiensis subsp. toguchini has been isolated from soil in Novosibirsk region. New subspecies forms elliptic crystals. Biologically and serologically it is different from other known subspecies. PMID- 2273189 TI - Changes in lipoprotein profiles during intense military training. AB - The effects of intense military training on lipoprotein concentrations were monitored in a group of 44 Navy trainees. Dietary intakes and lipoprotein profiles were obtained before and after 5 weeks of physical conditioning and after 5 days of continuous, extremely intense physical and psychological stress. Body weight did not change significantly and dietary intakes were consistently high in saturated fat and cholesterol. After physical conditioning, serum total cholesterol and triglyceride concentrations were unchanged, while high-density lipoprotein (HDL) concentrations increased 31% (p less than 0.05). After 5 days of severe stress, total cholesterol and low-density lipoprotein concentrations decreased 17.2% and 30%, respectively (p less than 0.05), whereas HDL concentrations increased 12.1%. These data indicate that marked changes in lipoprotein profiles occur, not only with long-term physical conditioning, but also with strenuous training that lasts several days, despite high energy, fat, and cholesterol intakes. PMID- 2273190 TI - Glycemic index of traditional Indian carbohydrate foods. AB - The glycemic index (GI) was determined in 36 non-insulin-dependent diabetes mellitus patients who were fed 50 g carbohydrate portions of six Indian conventional foods, including rice, a combination of rice-legume (Bengalgram, peas, and greengram), and a combination of rice-dal (greengram dal and redgram dal -- dal is dehusked and split legume). In addition to the GI, triglyceride (TG) responses of these foods were also determined. A higher GI was obtained for rice and for rice with peas; all other combinations yielded lower glycemic indices. However, all the foods produced significantly lower blood glucose response 2 hours postprandially as compared with blood glucose responses to a 50 g glucose load for the same group. No significant difference was observed for TG responses to the different foods. PMID- 2273191 TI - Diarrhea in diabetics: the role of sorbitol. AB - Diabetics often consume dietetic foods with sorbitol as the sweetener. Sorbitol, in amounts as little as 10 g. may produce diarrhea in healthy individuals. Sorbitol intolerance was studied in 12 diabetics and 23 nondiabetics. Similar numbers of diabetics (n = 10, 83.3%) and nondiabetics (n = 18, 78.3%) were found intolerant as judged by a greater than or equal to 20 ppm rise in postprandial breath hydrogen levels. Six diabetics (50%) and 13 nondiabetics (56.5%) developed abdominal symptoms after sorbitol ingestion. Subsequently, 100 diabetics and 100 nondiabetics were interviewed to determine the relationship between regular sorbitol consumption and abdominal symptoms. The interview revealed that (1) most individuals consuming sorbitol were unaware of its presence in their diet and (2) diarrhea was significantly (p less than 0.001) more prevalent in diabetics consuming sorbitol than diabetics not consuming it. We conclude that (1) many diabetics are intolerant to sorbitol and (2) regular sorbitol consumption may explain the "idiopathic" diarrhea in some diabetics. PMID- 2273192 TI - Superior calcium absorption from calcium citrate than calcium carbonate using external forearm counting. AB - Calcium absorption from calcium citrate was compared with that obtained from calcium carbonate in 20 normal women. It was measured by external forearm counting technique, where the ratio of forearm radioactivity after an oral dose of labeled calcium salt (containing 500 mg calcium) and after an intravenous injection of trace radiocalcium represented fractional calcium absorption. The fractional calcium absorption from calcium citrate was 39.2 +/- 8.6%, which was significantly higher than the 31.2 +/- 9.4% derived from calcium carbonate (p less than 0.001). Seventeen subjects displayed greater calcium absorption from calcium citrate. The remaining three patients, with a lower calcium absorption from the citrate salt, had high levels of calcium absorption from calcium carbonate. It is concluded that calcium is better absorbed from calcium citrate than calcium carbonate when these salts are taken on an empty stomach in most women. The exception might be those with optimum calcium absorption from calcium carbonate. PMID- 2273194 TI - Long-term effects of a vegetarian diet on the nutritional status of elderly people (Dutch Nutrition Surveillance System). AB - The health and nutritional status (anthropometry, and blood and urine biochemistry) of 44 Dutch apparently healthy vegetarians, aged 65-97 years, refraining from meat, fish, and poultry consumption, was assessed for insight into long-term consequences of ovo-lacto- or lacto-vegetarianism. The results indicate that in comparison to omnivorous elderly the vegetarian elderly (especially men) have aged successfully with respect to cardiovascular risk factors. In contrast, vegetarian elderly are at a higher risk for a marginal iron, zinc, and vitamin B12 status. Although several vegetarian elderly showed low levels of 25-hydroxyvitamin D in plasma and many had low values of 24-hr urine volume (per kg body weight), these values are not likely the result of a vegetarian diet per se. It is concluded that, although some nutrition-related risks are prevalent among vegetarian elderly, these risks can probably be prevented by lifestyle changes. PMID- 2273193 TI - Riboflavin intakes and status of morbidly obese females during the first postoperative year following gastroplasty. AB - Eighteen women participated in a prospective study to assess the need for supplemental riboflavin after gastroplasty. Three groups of five patients received either a placebo or 0.6 or 1.2 mg riboflavin daily for up to 12 months, except during months 4 and 7 when all participants were given a "one-a-day" supplement containing 1.7 mg riboflavin. Dietary intakes of riboflavin decreased from 1.43 +/- 0.17 mg before the operation to 0.70 +/- 0.07 mg at 3 months, and then increased to 1.02 +/- 0.17 mg by 6 months. Even at 12 months, only 33% of the subjects had dietary intakes greater than or equal to 1.2 mg. All those with total intakes less than or equal to 1.7 mg at 3 months had impaired riboflavin status, as indicated by an erythrocyte gluthatione reductase activity coefficient greater than 1.40 and an erythrocyte riboflavin concentration less than 372 nmol/L. In contrast, 62% of the same subjects had urinary riboflavin excretion in the acceptable range. Supplemental intake of 1.7 mg riboflavin appeared to prevent tissue depletion in all subjects. PMID- 2273195 TI - A synergism of antigen challenge and severe magnesium deficiency on blood and urinary histamine levels in rats. AB - The effects of severe and moderate magnesium (Mg) deficiency on blood and urinary histamine were studied in 36 male weanling Sprague-Dawley rats with or without IgE-stimulating antigen challenge. The rats were divided into six groups: two each on 50 (severely deficient), 300 (moderately deficient), and 2000 (control) ppm Mg diets without and with immunization with ovalbumin challenge on days 0, 14, and 29. Unimmunized severely Mg-deficient rats had significantly elevated urinary histamine which returned to normal by 22 days, but whole blood histamine was still significantly elevated at 36 days. Both blood and urinary histamine of immunized severely Mg-deficient rats were significantly higher than those of all the other groups throughout the study, particularly after the antigen challenge. There was a synergism of antigen challenge and severe Mg deficiency on blood and urinary histamine levels. The results suggest that severe Mg deficiency can aggravate diseases which are caused by abnormal histamine release after exposure to an IgE-stimulating antigen. PMID- 2273196 TI - Evidence for genetic determination of specific food choices of rats. AB - To study the contributions of genetics to food selection in an omnivorous species, rats of two strains and rats derived from reciprocal crosses of the two strains were compared. In addition, offspring of rats that accepted a specific food (ham) were compared with offspring of rats that refused the same food, and food selection of males was compared with that of females. Both homozygous nonobese Zucker rats and Zucker x Sprague-Dawley hybrid rats ate butterscotch, semisweet chocolate, and ground beef more often than Sprague-Dawley rats did. In contrast, Zucker rats ate ham more often than hybrid rats did, and hybrid rats in turn ate ham more often than Sprague-Dawley rats did. Rats produced by the two reciprocal crosses were similar to each other in food selection, ruling out maternal environment effects as the explanation for differences between Zucker and Sprague-Dawley rats. Hybrid rats selected for rejecting ham produced offspring that ate ham less often than did offspring of rats that accepted ham. Females ate semisweet chocolate more often than males did. We conclude that, contrary to the widely accepted view, heredity significantly influences specific food choices in an omnivorous species. PMID- 2273197 TI - Comparison of chemical, histomorphometric, and absorptiometric analyses of bones of growing rats subjected to dietary calcium stress. AB - Absorptiometric, histomorphometric, and chemical analyses of bones from growing rats fed diets with low (0.2%, w/w), marginal (0.4%, w/w), or adequate (0.8%, w/w) calcium (Ca) content with or without phytate were compared. Phytate was added to each diet in a molar ratio of 19:1 to calcium. Male weanling Sprague Dawley rats were fed one of the six diets for 8 weeks. At the end of 8 weeks, rats were killed, and mandibles, femurs, and tibias were removed. Bone density profiles were determined on the mandibles and femurs using single photon absorptiometry. Femurs were also used for calcium and phosphorus analyses. Tibias were used for histomorphometric analyses. Bone density of the femurs and mandibles increased as dietary Ca increased. The only effect of phytate addition measured was in the 0.8% calcium diet, where density was lower in rats fed the phytate-containing 0.8% calcium diet. Femur calcium concentration also increased as dietary Ca increased and was unaffected by addition of phytate. Femur phosphorus concentration was unaffected by dietary Ca levels but was increased by 10% when phytate was added to the diet. Bone density values were highly correlated with bone calcium and phosphorus levels (r = 0.94). Rats fed the 0.2% calcium diets had 20% lower mineralized bone area and 20% larger medullary cavity area than rats fed the other diets. Bone densitometry appears to be useful for determining changes in bone occurring in growing rats fed low, marginal, and adequate levels of dietary Ca. Bone density values also correlated well with chemically determined calcium and phosphorus concentrations and with histomorphometric data. PMID- 2273198 TI - Measurement of individual angiotensin peptides by HPLC-RIA. AB - Immunoreactive measurements of Angiotensin II in plasma, relate to a variety of angiotensin peptides with different biological activities. A method is described to differentiate these individual angiotensin peptides. It involves extraction of the peptides from plasma by reversible adsorption to phenylsilyl silica cartridges, separation by an isocratic, ion pairing high-pressure liquid chromatography technique and measurement of the appropriate fractions by radioimmunoassay. In umbilical venous plasma molar concentrations of the smaller angiotensin fragments were found to range between 16 and 25% of the concentrations of the angiotensin II octapeptide. Because some angiotensin antisera show higher affinity for the smaller peptides than for the octapeptide, concentrations of angiotensin II, measured by radioimmunoassay, may be overestimated by up to 35% unless the various angiotensin peptides are adequately separated. PMID- 2273199 TI - Quantitation of immobilized proteins. AB - A method for the quantitative determination of immobilized proteins based on the binding and subsequent elution of Coomassie Blue R is presented. Also presented is a method for the immobilization of proteins in solution by entrapment in polyacrylamide. These entrapped proteins are then available for use in the assay method presented. Other analytical procedures can also be performed on the entrapped proteins, either alone or in combination with the protein quantitation. The dye binding and elution method presented provides a sensitive and, in most applications, rapid method for the quantitative detection of immobilized proteins. Rather than immobilization being an obstacle to the assay method, this approach utilizes the advantages of immobilization for the removal of excess reagents. Application of this approach to several types of immobilized protein are presented. PMID- 2273200 TI - Identification of bacterial periplasmic glycine betaine-binding protein after electrophoresis and affinity labeling. AB - Antibodies were elicited in rabbits against periplasmic proteins obtained by cold osmotic shock from the Gram-negative eubacterium Rhizobium meliloti. When analyzed by crossed immunoelectrophoresis (CIE), the periplasmic proteins gave rise to 20 distinct immunoprecipitates corresponding to the same number of bands in polyacrylamide gel electrophoresis (PAGE) under non-denaturing conditions and in SDS-PAGE. The periplasmic glycine betaine-binding protein (GB-BP) was identified by autoradiography after affinity labeling with [14C]glycine betaine in PAGE and in CIE gels. The binding proved to be quite specific to glycine betaine, since the GB-BP was not labeled by choline (a metabolic precursor of glycine betaine in Escherichia coli and Rhizobium meliloti) and 15 distinct L amino acids, including L-proline which, like glycine betaine is also an osmoprotectant. Affinity labeling of the GB-BP with [14C]glycine betaine after protein separation by PAGE or CIE is a simple and sensitive technique permitting the GB-BP to the unambiguously detected and identified in samples of complex protein mixtures containing down to 2 micrograms of GB-BP in PAGE and only 0.2 micrograms in CIE. PMID- 2273201 TI - Synthesis of an hydrophilic, pK 8.05 buffer for isoelectric focusing in immobilized pH gradients. AB - The synthesis of a new, pK 8.05 acrylamido weak base for isoelectric focusing in immobilized pH gradients (IPG) is here reported. This compound N,N-bis(2 hydroxyethyl)-N'-acryloyl-1,3-diaminopropane is strongly hydrophilic, and thus inhibits any potential hydrophobic interaction among proteins and the grafted basic groups in an IPG matrix. In addition, this novel buffer represents a step ahead towards the goal of closing the 'gap' between the commercially available Immobilines, pK 7.0 and 8.5. Owing to the large distance between these two neighboring pK values, it is difficult to arrange for linear narrow pH gradients in this region. IPG compositions obtained with this new buffer give highly linear pH gradients and protein profiles identical to those obtained with commercial Immobilines. PMID- 2273202 TI - Two-dimensional maps in the most extended (pH 2.5-11) immobilized pH gradient interval. AB - In conventional isoelectric focusing in soluble, amphoteric buffers, it has been quite difficult to produce two-dimensional (2-D) separations in pH intervals greater than pH 4-8. In general more alkaline proteins were analyzed by non equilibrium IEF in the first dimension. Even with the advent of immobilized pH gradients (IPG), separations could be extended to pH gradients not wider than pH 3-10, due to a lack of suitable buffers. Since more acidic and more alkaline acrylamido buffers have recently been synthesized, we have been able to optimize what is believed to be the widest possible immobilized pH gradient, a pH 2.5-11 span. We report here for the first time 2-D separations of total tissue lysates in such extended pH 2.5-11 gradients. It appears that, with the IPG technique, close to 100% of all possible cell products can be displayed in a single 2-D map. PMID- 2273203 TI - A field study on residues of four insecticides used in strawberry protection. AB - In 1986 strawberry plots were treated with dimethoate, malathion, permethrin and cypermethrin at 80% bloom of primary flowers. In 1987 the plots were sprayed with dimethoate, malathion and permethrin at 30% bloom. Residue analysis of these insecticides on the flowers were analyzed using solvent extraction and gas liquid chromatography. Residue analysis at 0 to 18 days on flowers and fruit showed an exponential decrease. Organophosphates tended to degrade more quickly than synthetic pyrethroids. The results are discussed in the context of an integrated pest management program. PMID- 2273204 TI - Calcitonin and estrogens. AB - Estrogen deficiency is thought to be the main factor leading to postmenopausal osteoporosis (PMO). A role for calcitonin (CT) has been proposed as mediator of estrogen action on bone, and therefore, as pathogenetic factor of PMO. However, this hypothesis is still controversial. To further analyze the relationships between estrogens and CT in PMO, we studied the effects of one-year estro/progesterone therapy on CT secretory reserve, evaluated by a calcium infusion test in 12 postmenopausal women, as compared to 12 placebo treated subjects. In the hormone treated group, blood levels of CT showed a progressive increase during the study and a plateau was reached at 9 months, indicating that CT production achieved a new steady state. Hormonal therapy also significantly improved the CT response to calcium stimulation test. A concomitant increase of vertebral bone mass was observed in the hormone treated women, who also maintained initial bone density of femoral dyaphyses. On the contrary, the placebo treated group continued to lose bone mineral at both sites. Our study demonstrates that estrogens regulate CT secretion in postmenopausal women; thus, CT may be considered a mediator of estrogen action on bone. PMID- 2273205 TI - Height and weight of nursery and primary school population from Torre del Greco, a Campania town, Italy. AB - Height and weight were measured in 7902, 3.5-11-year-old children from Torre del Greco nursery and primary school and arranged in centiles by cumulative frequencies calculation after sorting into ascending order measurements and counting up from the bottom. Our population height and weight measurements were compared to Tanner's by chi-square test. Our population seems to be taller and fatter with respect to Tanner's. Two possible explanation can be suggested: 1) British data are findings published several years ago; 2) Modified conditions of life in South-Italy in the last 30 yr, especially increased feeding availability can explain both increased height and frequent weight excess observed. These data suggest that for a correct auxological evaluation it seems useful to compare children not only to Tanner's standards but to centiles derived from the same population. PMID- 2273206 TI - Interaction of glucose and pyridostigmine on the secretion of growth hormone (GH) induced by GH-releasing hormone (GHRH). AB - In order to investigate the mechanisms by which hyperglycaemia induces an inhibition of GHRH-induced GH release, we gave the following treatments to seven normal men: a) GHRH 100 micrograms iv; b) pyridostigmine (PD) 120 mg po 60 min before GHRH; c) glucose 250 mg/kg iv as a bolus (10 min before GHRH) plus 10 mg/kg/min until the end of the test; d) glucose pyridostigmine and GHRH as above. Glucose significantly reduced GHRH-stimulated GH levels, whereas PD significantly enhanced them. When PD and glucose were given together, the effect on GHRH stimulated GH secretion was not different from the algebraic sum of the single effects of the two substances. Thus glucose seems to be able to exert its inhibition, at least partially, also when pyridostigmine is coadministered. PMID- 2273207 TI - Acute water intoxication after intranasal desmopressin in a patient with primary polydispsia. AB - Only a few cases of severe acute water intoxication (AWI) due to intranasal desmopressin have been reported, none of which occurred in patients with primary polydipsia. We describe a case of AWI with semicoma and convulsions, due to intranasal desmopressin, in a 32-year-old patient with dipsogenic diabetes insipidus. Previous reported cases of AWI due to desmopressin are discussed. The importance of ruling out primary polydipsia when this drug is used, not only for central diabetes insipidus but also for other current indications such as classic hemophilia, is stressed. PMID- 2273208 TI - Asymptomatic parathyroid adenoma manifested by intratumoral hemorrhage. AB - A 48-year-old woman whose past history was unrevealing presented with sudden swelling of the neck with pain and dysphonia. Neck ultrasonography suggested the possibility of hemorrhage in a parathyroid adenoma. Surgical exploration revealed a hemorrhagic parathyroid adenoma of the chief cell type. This event is exceedingly rare, but should be considered in the differential diagnosis of suddenly appearing masses of the neck region. PMID- 2273209 TI - Acromegaly, multinodular goiter and silent polyostotic fibrous dysplasia. A variant of the McCune-Albright syndrome. AB - A 36-year-old woman is reported with a possible variant of the McCune-Albright syndrome. The triad was incomplete because of the absence of skin pigmentation and since the sexual precocity was not evident. The presence of a pituitary mass and the secretory dynamics of growth hormone and prolactin were suggestive of a mammosomatotroph cell adenoma. A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. Unusual was the silent evolution of the polyostotic fibrous dysplasia, which was only fortuitously discovered during magnetic resonance imaging of the pituitary region. Treatment of the acromegaly with the long-acting somatostatin analogue octreotide resulted in an important inhibition of the GH secretion and in a reduction of the volume of the pituitary adenoma. PMID- 2273211 TI - Resistance to a long-acting somatostatin analog (SMS 201-995) reversed by surgery in acromegaly. AB - A 42-year-old woman had acromegaly and a large macroadenoma with supra- and parasellar extension. Her GH levels (median 85 ng/ml, range 63-170 ng/ml) were not responsive to TRH (200 micrograms iv), GHRH (100 micrograms iv) and bromocriptine (Br 2.5 mg po) acute tests; Sm-C level was 8 U/ml. She was treated with octreotide (SMS) (up to 1500 micrograms daily) for 3 months. No changes of clinical, biochemical and radiological findings were seen, therefore she underwent transsphenoidal surgery. After surgery, hypopituitarism and diabetes insipidus appeared: GH levels remained high (median 45 ng/ml; range 37-56 ng/ml), but became responsive to Br acute test. The patient was given SMS again, and this resulted in clinical improvement, marked reduction of GH and Sm-C levels and slight shrinkage of the residual tumor. Speculative hypotheses about this previously unreported phenomenon might be either an excess of both GHRH and somatostatin, caused by a primary increase of dopaminergic tone, or a primary excess only of GHRH; in both cases the surgical lesion of the hypothalamic pituitary region might have impaired the neurohormones inflow to the residual pituitary and so let SMS and Br exert their inhibitory actions on GH secretion. PMID- 2273210 TI - Pituitary granuloma and pyoderma gangrenosum. AB - Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy. PMID- 2273212 TI - Hypothyroidism and goiter during interleukin-2 therapy. PMID- 2273214 TI - Health policy and the politics of research in the United States. AB - During the past decade research has been more important to the health policy making process in the United States than at any time in the past. This article describes and assesses three competing normative models for research on health affairs: economizing, social conflict, and collective welfare. The three models provide a context for the history of research bearing on health policy in the past half century, with particular pertinence to the years since 1980. The article concludes with a discussion of some of the consequences of the new legitimacy of research. PMID- 2273213 TI - The role of growth factors in the pituitary. PMID- 2273215 TI - Research, policy, and the National Health Service. AB - The National Health Service is a system designed to bring about a rational use and distribution of resources yet which largely ignores the contribution of the research community. With a relatively closed health policy arena, there are few customers for policy-oriented research. With responsibility for funding research concentrated at the center and responsibility for delivering services at the periphery, the research community finds itself in limbo. In comparison to both the U.S. and Canada, Britain therefore offers an example of research both underfinanced and undervalued. However, research has made some significant contributions in areas where there has been a perceived use for its findings to support service developments. And the changes now being introduced in Britain's NHS are likely to create a new market for research as the system adopts some North American ideas and becomes less consensual and more pluralistic. PMID- 2273216 TI - Finding audiences, changing beliefs: the structure of research use in Canadian health policy. AB - The impact of research information depends on its ability to change beliefs or policy assumptions within the relevant audiences. As a hybrid of American and British systems, Canada's chosen decision-making structure for policy-making and its legislative framework for health insurance make these audiences unclear and not readily accessible. This factor and historical characteristics of the research community which made them only partially responsive to the values of decisionmakers provide an explanation for the limited past use of research information in Canadian health policy. More recently, improved responsiveness by researchers and an emerging definition of the audiences by legislative policymakers are bringing about a gradual increase in the potential impact of research at the levels of administrative and clinical policy. Because of continuing decision-making constraints on legislative policy, however, impact at this level is predicted to remain diffuse, with only cautious acceptance of the changes in beliefs implied by research. PMID- 2273217 TI - Legislative incapacity: the congressional role in environmental policy-making and the case of Superfund. AB - Congress plays a central role in national environmental policy formation but appears ill equipped to set policy priorities and devise integrative legislation. Fragmentation of authority among a multiplicity of committees and subcommittees, especially in the House, contributes to these problems. This pattern is evident in the evolution of Superfund, the national program to clean up abandoned hazardous waste sites. The prolonged process of reauthorization in the 1980s contributed to serious program delay and failed to resolve a number of fundamental questions concerning the national cleanup effort. Institutional reforms could contribute to a more effective congressional role in future environmental policy deliberations. PMID- 2273218 TI - Physician-management relationships at HCA: a case study. AB - The questions of whether Hospital Corporation of America (HCA), a for-profit hospital company, fostered an environment detrimental to the physician-patient relationship during the period of implementation of the Medicare Prospective Payment System (PPS) was explored. The transition to PPS provided an opportunity to evaluate whether hospital ownership differences affected responses to a payment system which encouraged institutional intervention in the practice of medicine. A case study approach was used to observe the influence of the then largest for-profit hospital corporation upon physicians' medical practice in four owned hospitals. Findings indicated that HCA hospital managers were most directly influenced by the local competitive environment and their own personal agendas in responding to PPS incentives. Corporate influence actually softened payment system incentives to intervene in medical practice by providing a generous supply of capital, and by fostering a corporate culture conducive to cooperative relationships with physicians. Better public understanding of the determinants of hospital behavior is needed to preserve or enhance important social goals such as the physician-patient relationship; easily measurable characteristics such as ownership or bed size explain little about hospital behavior or motivation. PMID- 2273219 TI - Estimating the extent of Medicaid spend-down in nursing homes. AB - Although it is commonly thought that a very high proportion of private-pay nursing home patients become eligible for Medicaid during their stay, few national studies have been conducted to determine the extent of Medicaid "spend down." The discharged resident survey of the 1985 National Nursing Home Survey was analyzed to determine the extent of spend-down among elderly nursing home patients during a single nursing home episode, the proportion of patients who remained Medicaid or private payers throughout their stay, and how the measures varied by patient characteristics. Overall, during a single nursing home episode only 10 percent of nursing home patients who entered as private payers received Medicaid at discharge. Roughly one-third of nursing home patients remained on Medicaid throughout their stay, and another third remained private payers throughout their stay. PMID- 2273220 TI - Health economics: a report on the field. AB - This study documents who health economists are, what they do, and what they think about professional and policy issues. Using primary data obtained through a mail survey of 518 health economists, we found that health economists are well trained by the standards of their profession. Most are employed in noneconomics departments in universities, where they spend their time very differently from their cousins in economics departments. There is a clear dichotomy in policy views among health economists. The characterization of the field as composed of "narrow" neoclassicists and "broad" eclecticists is supported by our data. PMID- 2273221 TI - Paying the Hospital. Essay review. PMID- 2273222 TI - Hospital behavior in a competitive market. Essay review. PMID- 2273223 TI - Environmental accidents and public responsibility. Essay review. PMID- 2273224 TI - Surveillance of hospital infections in the United Kingdom. PMID- 2273225 TI - Hospital-based routine HIV testing programs. PMID- 2273226 TI - An effective educational program to reduce the frequency of needle recapping. AB - We developed an educational program that reported the rate of needle recapping to healthcare workers, in conjunction with emphasis on appropriate disposal procedures. Over 12 months, the rate of recapping needles used for venipuncture and for percutaneous medication injections fell from 61% to 16% (p less than .0001). Over the same period, the recapping of needles used primarily for intravenous (IV) administration fell from 44% to 33% (p = .03). Re-evaluation of the rate of recapping eight months later showed a continuation of these lowered rates. Needlestick injuries were too few in number during the study period to detect any change accompanying the decreased recapping rate. We conclude that programs that report back to employees their rate of recapping can significantly reduce this activity in the disposal of needles used for venipuncture and for percutaneous medication injections. While such reporting may reduce the rate of recapping of needles used for IV administration, the effect is not nearly so marked. Modifications in design remain the most promising approach to preventing needlestick injuries from recapping needles used for IV administration. PMID- 2273227 TI - Increasing prevalence of methicillin-resistant Staphylococcus aureus in the United States. AB - In the period 1975 to 1981, methicillin-resistant Staphylococcus aureus (MRSA) emerged as an important nosocomial pathogen in tertiary care centers in the United States. To determine if the prevalence of this organism has continued to increase, a questionnaire was sent to hospital epidemiologists in 360 acute care hospitals. A total of 256 (71%) of the 360 individuals responded. Overall, 97% (246/256) of responding hospitals reported having patients with MRSA in the period 1987 through 1989. Respondents in 217 hospitals provided estimates of the number of cases seen in 1987, 1988 and 1989. The percentage of respondents reporting one or more patients with MRSA increased from 88% in 1987 to 96.3% in 1989 (p = .0008). The percent of respondents reporting large numbers (greater than or equal to 50) of cases per year increased from 18% in 1987 to 32% in 1989 (p = .0006). Increasing frequency of large outbreaks was observed in community, community-teaching, federal, municipal and university hospitals. PMID- 2273228 TI - Postoperative group A beta-hemolytic Streptococcus outbreak with the pathogen traced to a member of a healthcare worker's household. AB - A cluster of four group A beta-hemolytic Streptococcus postoperative wound infections was investigated at a community hospital. The serotypes of the Streptococcus isolated from all four cases, an asymptomatic anesthesiologist and one of his household members were M nontypable T28. During the outbreak period, December 1988, the infection rate among the 40 patients of the anesthesiologist was 7.5%. Among other patients not having contact with this healthcare worker, it was 0.09% (p = .0002 Fisher's exact test). This is only the second reported Group A beta-hemolytic Streptococcus hospital outbreak in which the pathogen was traced to a member of a healthcare worker's household. Early outbreak detection and intervention limited the extent of the outbreak. PMID- 2273229 TI - Position paper: the HIV-infected healthcare worker. The Association for Practitioners in Infection Control; The Society of Hospital Epidemiologists of America. PMID- 2273230 TI - Hospital chaplains--a neglected resource? PMID- 2273231 TI - Israeli nurses in intensive cardiac care units (ICCUS): stress, satisfaction and coping. PMID- 2273232 TI - Training nurses for intensive care. PMID- 2273233 TI - Problems in the decision making process: a review. AB - Decision making is an integral part of the intensive care nurse's role, but many factors can disrupt this process. It is important that the nurse has an understanding of how defective decision making patterns can develop. Experience, the role of the nurse, uncertainty and conflict all exert major influences on the decision making process. The conditions that determine what type of decision making pattern emerges are; the seriousness of the risks as a result of the decision; if there is hope of finding a better solution; and how much time is available to search for the solution. The patterns that may emerge include vigilance, complacency, defensive avoidance and hypervigilance. Vigilance is said to be the optimum pattern, this is when all alternatives to the decision are analysed and interpreted in an unbiased manner. Defensive avoidance is the decision makers attempt to avoid or postpone the stress of the decision. It is manifested by procrastination, shifting of responsibility or rationalisation. Hypervigilance, or panic, represents a frantic search for a solution and a shifting back and forth between alternatives with a failure to see obvious faults in the possible solutions. PMID- 2273234 TI - Dealing with bereavement in critical care. PMID- 2273235 TI - A chaplain's personal view of intensive care. PMID- 2273236 TI - Calculating haemodynamic parameters and interpreting arterial blood gas samples using a pocket computer. AB - The pocket computer, being both cheaper and more powerful, has brought computing within the realm of many intensive care nurses. The problem, however, is one of a lack of dedicated software that is able to perform clinical tasks or calculations; thus making the nurse's work easier. The aim of this article, therefore, is to present two programs for a popular pocket computer that will not only introduce the nurse to simple BASIC programming language, but will also provide useful bedside information. PMID- 2273237 TI - Policy and procedure manual: keeping a high quality manual. AB - Policy and procedure manuals are now commonly used in hospitals. The policy and procedure manual provides critical care nurses with a wealth of information. Policies are developed to guide the staff to perform nursing care adequately. Together policies and the corresponding procedures let critical care nurses know how to proceed to meet the organisation and the unit goals. As critical care expands the number of policies increases, which may make it more difficult to find a specific policy quickly. Critical care nurses need to look at other solutions for communicating some necessary pieces of information and check to make sure that policy is stated briefly, to the point and logical. It is also necessary to check to see if the information included in the manual is policy and associated procedures. If it is drug information, equipment usage, standards of care, or patient/family teaching material it could be incorporated in a different format or separate manual. As care givers nurses must monitor policies and procedures that are written and make sure they are simple to read, logically written, and easy to find. PMID- 2273238 TI - Multifactorial inheritance of common white markings in the Arabian horse. AB - The results of a previous study were compatible with the hypothesis that common white facial markings in the Arabian horse have a multifactorial mode of inheritance. I expanded that study to (1) include the legs and therefore obtain insight into the heritability of common white markings in all peripheral regions (face and legs) of the Arabian horse and (2) investigate the influence of sex and the genotypes that produce the bay and chestnut phenotypes on the variation in common white markings. Both studies were based on computerized data obtained from the Arabian Horse Registry of America, Inc. Each leg of a horse was scored from 0 to 5 depending on the amount of whiteness present, and the four leg scores were added to obtain the total leg score for each horse. The facial region was divided into five areas, and each horse was given a score from 0 to 5 according to the number of areas with whiteness. Sire families were analyzed in which each sire family consisted of a sire, his foals, and the dams of those foals. There was a correlation between white facial scores and white leg scores, suggesting that both types of white markings are influenced by the same genetic mechanism. Sire foal and dam-foal regression analyses were compatible with the hypothesis that common white leg markings also show multifactorial inheritance. Although the results support the model that additively acting genes (polygenes) influence the presence and extent of common white markings, the results also show that males are slightly more marked than are females and that chestnut horses are more heavily marked than are bay horses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273239 TI - Inbreeding depression in insular and central populations of Peromyscus mice. AB - We tested the hypothesis that small, isolated populations would show less depression in fitness when inbred than would large, central populations. Laboratory stocks of Peromyscus leucopus and P. polionotus were established from insular, peninsular, and central populations. The isolated populations had one third to one-half the genic diversity of central populations. Responses to inbreeding were highly varied: some populations had smaller litters, others experienced higher mortality, some showed slower growth rates, and one displayed no measurable effects when inbred. These results suggest that inbreeding depression is controlled by a small number of genes and that the size of the genetic load depends on which alleles are present in the founders of a population. The severity of fitness depression in inbred litters did not correlate with initial genic diversity of the stocks nor, therefore, with the size of the wild populations. Fitness measures appeared linearly related to the inbreeding coefficient of the liters, with no diminution of deleterious effects through subsequent generations of inbreeding. Thus overdominance of fitness traits probably contributed as much to the genetic load as did deleterious recessive alleles. The inbreeding level of the dam negatively affected the size, growth, and survival of litters only in genetically diverse populations, indicating that the load of recessive alleles negatively impacting maternal care may have been reduced by selection in the more peripheral populations during past bottlenecks. PMID- 2273240 TI - Biological monitoring of human exposure to metals. AB - Biological monitoring of exposure to metals and metalloids involves not only determination of these elements in selected body fluids and tissues but, in some cases, also determination of a certain biochemical indicator which signalises the presence of the monitored element in the organism. Biological monitoring of occupational exposure to metals has a long tradition whereas biological monitoring of exposure in general environment has developed more intensively only in the past two decades. New information about the toxic effect of some metals and metalloids and about their kinetics of absorption, distribution and excretion in experimental animals, and particularly in man, is necessary for elaborating suitable biological exposure tests. Of current interest is also the movement of persistent noxae in the environment, seen from the ecologic view point. This report outlines the present state of the problem in Czechoslovakia. PMID- 2273241 TI - Using satellite data to forecast the occurrence of the common tick Ixodes ricinus (L.). AB - To forecast the incidence of the common tick, Ixodes ricinus, the authors used the finding that some types of vegetation may indicate the presence of the tick. To obtain the necessary information in a scope which would enable its practical application in medicine to prevent populational exposure to ticks, remote sensing data were utilized as obtained from the Multispectral Scanner operating aboard Landsat 5. A file was selected from the full scene representing a territory which measured 41 by 41 kilometers and in the centre of which there was an area known to have consistently high tick numbers, as revealed in a 25-year continuous study of I. ricinus, and which proved to be a natural focus of tick-borne encephalitis. This area (Potepl) was taken as a model and was compared with its surroundings. Six landscape classes were examined (1--coniferous forest, 2--leaved forest, 3- mixed forest, 4--water basins, 5--glades, 6--housing developments), the former three being of crucial importance to evaluate the probability of tick presence. The 6th category is significant in assessing human exposure to ticks. Data processing was carried out by supervised classification using the Baye's decision rule of maximum likelihood. The findings were obtained both in a graphic form and in the form of statistical reviews as regards the presence of appropriate landscape categories. PMID- 2273243 TI - Current issues in seamen's labour intensity (a review of Soviet literature). AB - In view of the changing nature of seamen's labour over the last decades, a decrease in the proportion of manual work and increasing levels of operator activities, the evaluation of the intensity of labour among maritime and riverine ship crews becomes an important criterion of regulating labour regimens and adopting measures aimed at enhancing work ability as well as diminishing fatigue and morbidity rates. The methodological approaches valid in other branches of the national econom cannot be fully utilized for the assessment of seamen's labour intensity. The author summs up published data on the optimization of labour intensity (introduction of prolonged regimens of work on board a ship and rest ashore, employment of physical factors, medical drugs, psychological relaxation etc.). PMID- 2273242 TI - On the health status of subjects employed at factories manufacturing enzyme preparations. AB - Intensive exposure to the antigens of industrial strains of microorganisms and their metabolites resulted in the suppression of cellular immunity and the activation of some components of humoral immunity (IgM) and neutrophil bacterial activity in workers employed in the manufacture of enzymes. Industrial microflora (Bac. Subtilis and Asp. awamori) utilized in the technological process of microbiological synthesis of enzyme preparations was isolated from the skin in 34.25% and 16.44% and nasal and pharyngeal mucosa in 39.73% and 28.77% workers respectively. On clinical examination, most frequently affected were the skin (70.4% tested subjects), nasopharynx (64.4%), bronchopulmonary apparatus, oesophagus and GIT. Endoscopic tests confirmed the diagnoses in detecting producing strains on bronchial and oesophageal mucosa in 23.08% workers. In view of the low efficacy of employed individual protective equipment, the prevention of occupational pathology should be directed towards development or improvement of existing technological processes which would rule out intensive exposure of the human organisms to producing strains. PMID- 2273244 TI - Effect of a zinc-deficient diet on nitrogen balance in rats. AB - The effects of a zinc-deficient diet (1.5 mg/kg) on nitrogen balance in rats, fed ad libitum during 30 days, was tested. Three nitrogen balances, each of 5 days, were done on the 4th, 15th and 25th days. A pair-fed group, with a supplemented diet at 80 mg/kg of zinc, was used as control. No significant differences (P less than or equal to 0.05) in any nitrogen balances for True Digestibility, Operative Biological Value and body weight were found. Nevertheless a trend was observed in all studied variables, indicating that the proteins of the control diet were better utilized than those of the zinc-deficient ones. The variation of the Biological Value of the proteins in the zinc-deficient group along the experimental period was similar to the control group. PMID- 2273245 TI - Filamentous micromycetes in working environment. AB - We investigated quantitative and qualitative representation of the germs of filamentous micromycetes in the samples of plant origin which were taken in connection with objective and subjective changes of health state of employees' respiratory tract from various factories. On the basis of the received results it is required to deal with questions on the determination of certain acceptable amount of micromycetes in the environment, and the like. It is necessary to objectivize the degree of risk in workers at the professional exposition of micromycetes or their toxins. PMID- 2273246 TI - Do influenza epidemics spread to neighbouring countries? AB - This study compares the main causes of influenza epidemics reported in Czechoslovakia (CSR) and the German Democratic Republic (GDR) during the 9 seasons between 1980 and 1988. The influenza epidemics due to identical virus types were experienced in the two countries in the 1980, 1984 and 1986 seasons, and of these only the 1984 epidemic associated with A-strain influenza A/Chile/1/83 (H1N1) virus could be demonstrated to spread from the eastern parts of the CSR to the northern areas of the GDR. This implies that influenza epidemics due to identical drift variants spread only exceptionally from one country to the other during the period of observation, in spite of a busy tourist activity across the borderline. PMID- 2273247 TI - Studies on immunomodulatory properties of isoniazid. III. Effect of isoniazid on proliferation of interleukin-dependent and interleukin-independent cell line. AB - The effect of various concentrations of isoniazid on proliferation of the interleukin 2-dependent cell line, HT-2 and continuous T cell line Jurkat was studied. It was found that high doses of isoniazid increased proliferation of the HT-2 cells in presence of suboptimal doses of interleukin 2. Low doses had no effect on proliferation. The unstimulated Jurkat cells increased proliferation in presence of low doses of isoniazid while phytohemagglutinin-stimulated cells responded to high doses of the drug only. It is hypothesized that biphasic effect of isoniazid is caused by cumulation of direct and indirect effects of T cell activation as well as toxic influence on the cells. PMID- 2273248 TI - Production of substances with thymosin-like activity by B- and T-lymphocytes. AB - The authors investigated the ability of various lymphocyte subpopulations to synthesize substances with thymosin-like activity under the influence of thymostimulin, a preparation of active thymic factors. Experiments carried out on T- and B-mice revealed that only T-lymphocytes synthesized thymosin-like substances in response to thymostimulin administration. Thus induced substances differed significantly from those which ensure the serum activity of normal animals in that their thermostability is by far greater. The feasibility was also explored of inducing by thymosin the in vitro synthesis of substances with thymosin-like activity in cells derived from a variety of lymphoid formations of thymectomized mice. The serum of thymectomized lethally irradiated recipients of lymph node and spleen cells pretreated with thymostimulin was found to contain, 4 h after the transfer, relatively high levels of substances with thymosin-like activity. Contrariwise, the pretreatment of bone marrow cells with thymostimulin resulted in declined levels of substances with thymosin-like activity in recipient sera as compared to those in B-mice which were given untreated bone marrow cells. The incubation of bone marrow cells in a medium containing substances with thymosin-like activity caused a decrease in that activity. Thus, the biologically active thymic factors were shown to induce the synthesis by T cells of substances with thymosin-like activity. PMID- 2273249 TI - Fimbrial hemagglutinins in Klebsiella pneumoniae. AB - Eleven Klebsiella pneumoniae strains were isolated from urine specimens which were examined for their ability to produce hemagglutinins (HAs). Bacteria were grown under various culture conditions. Suspension of bacteria grown in broth or on Phosphate-buffered nutrient agar (PBA) were tested for agglutination in the presence and absence of 2% (w/v) D-mannose, on rockedtiles at 4 degrees C and ambient temperature with mangroup-O(M), fowl(F), ox(O), guinea-pig(G), horse (H), rabbit (R) and sheep (S) erythrocytes and tannic acid treated, but not fresh oxen erythrocytes. Each of the 11 strains was hemagglutinating. Ten strains (99%) producing two or three hemagglutinins (HAs), were multiple hemagglutinating. One strain produced only mannose-resistant, Klebsiella, the "Tanned ox hemagglutinin" (MR/K-HA). Solely mannose-sensitive hemagglutinin (MS/HA) was not produced by any of the strains. No mannose-sensitive hemagglutinating strains acted on sheep erythrocytes. Three main kinds of hemagglutinin (HA) were detected. These were: (a) a mannose-sensitive hemagglutinin (MS-HA); (b) a mannose resistant, Klebsiella, the "tanned ox hemagglutinin (MR/K-HA); (c) mannose-resistant, Proteus hemagglutinin (MR/P-HA). All strains (100%) produced MR/K-HA, 45% of MR/K HA+ strains produced MR/P-HA at 37 degrees C and 99% of all strains produced MS/HA, MR/P-HA activity was never dependent on MR/K-HA: Electronmicroscopic examination of bacteria showed that all strains were fimbriate. PMID- 2273250 TI - Kinetic immunochemical studies of IgG production during local and systemic anti influenza immune response in rats. AB - The kinetics of anti-influenza IgG antibodies in serum and nasal wash during the local and systemic immune response in rats was studied. The influenza virus A/HK/1/68 (H3N2) was injected by two different routes--intranasally and subcutaneously in the hind footpads. The proliferation of the Ig-forming cells in the popliteal and paratracheal lymph nodes either local or distant according to the mode of virus administration was also studied. The results obtained during the primary and secondary immune response suggested that an atypical immunization also produced a strong immune response in the distant lymph nodes. The nature of the secondary immune response supports the concept of migration of the activated lymphocytes from the peripheral lymph nodes to the natural portal of entry of virus thus giving rise to specific clonal population. PMID- 2273251 TI - Migration of 99mTc-labelled syngeneic lymphocytes in the rat. Biological and theoretical models predict radiation damage and poor scintigraphic detectability. AB - The possibility of obtaining useful scintigrams of secondary lymphoid organs after infusion of syngeneic lymphocytes labelled with technetium-99m (99mTc) was explored in a rat model. Thoracic duct lymphocyte (TDL) accumulation in various organs was measured with both 99mTc and 51Cr labelled cells, the latter processed with a method that has been shown not to damage lymphocytes. 99mTc labelled TDL did not localize properly in the lymph nodes and spleen. We could not visualize lymph nodes in scintigrams, neither could we demonstrate any difference between normal and hyperplastic spleens. Our conclusion is that radiation from the 99mTc label readily influences lymphocyte migration so that useful scintigraphy in rats and other small experimental animals becomes impossible. This was supported by results from culture experiments with 99mTc labelled, radiosensitive mouse haemopoietic progenitor cells. Theoretical considerations, including the calculations of lymphocyte self-irradiation and signal/noise ratios during scintigraphy of rat tissues, supported our conclusion that scintigraphy in small animals, to disclose the physiological migration of lymphocytes, may be impossible with the present sensitivity of gamma cameras. PMID- 2273252 TI - An ELISA employing a Haemophilus influenzae type b oligosaccharide-human serum albumin conjugate correlates with the radioantigen binding assay. AB - An ELISA measuring total Ig antibodies to the capsular polysaccharide of Haemophilus influenzae type b (HbPs) in human sera using an antigen composed of Haemophilus b oligosaccharides conjugated to human serum albumin (HbO-HA) was shown to have an excellent correlation to the radioantigen binding assay (RABA). When 214 sera with different anti-HbPs levels were assayed for total Ig by HbO-HA ELISA and by RABA the correlation coefficient was 0.917 and the paired t test p value was 0.575. Use of competitive ELISA employing soluble HbPs, HbO-HA and human albumin as competitors, showed that the HbO-HA ELISA was specific for antibodies to HbPs. The HbO-HA ELISA yielded reproducible results both within and between laboratories. The HbO-HA ELISA can also be used to determine the isotype of anti-HbPs antibodies by using isotype specific enzyme conjugates. The sum of the IgG, IgA and IgM HbO-HA ELISA results had excellent correlation to the RABA results (correlation coefficient = 0.976). Thus, the HbO-HA ELISA can be substituted for the classical RABA and also be utilized for quantitating the isotype of the anti-HbPs antibodies. PMID- 2273253 TI - The specific blocking of an IgG dependent erythrophagocytosis assay by protein G and ELISA determination of in situ bound IgG on erythrocytes of normal donors. AB - We report the development of an in vitro erythrophagocytosis assay in which the level of phagocytosis reflects the number of IgG molecules bound to the erythrocyte. This assay is sensitive to 300 IgG per erythrocyte above background levels. Blocking the Fc of the bound immunoglobulin with protein G totally blocks macrophage recognition of the opsonized red cell and prevents Fc-gamma-dependent phagocytosis. An accurate, reliable, easily performed CELL-ELISA (cellular ELISA) for the determination of very low levels of IgG on the human erythrocyte membrane has been developed. This CELL-ELISA is based on the use of biotin conjugated to goat anti-human IgG (GaHIgG) and streptavidin conjugated to alkaline phosphatase. The CELL-ELISA can be accurately performed on either fresh or glutaraldehyde fixed erythrocytes. When a population of healthy young adults was studied an average of 126 +/- 14 IgG molecules per erythrocyte were detected. PMID- 2273254 TI - Purification of immunotoxins containing the ribosome-inactivating proteins gelonin and momordin using high performance liquid immunoaffinity chromatography compared with blue sepharose CL-6B affinity chromatography. AB - Comparable amounts of the ribosome-inactivating proteins (RIPs) ricin A chain, gelonin and momordin were allowed to bind to Blue Sepharose CL-6B (immobilised Cibacron Blue F3GA) in phosphate buffer, pH 7.5, and were then eluted quantitatively with buffer containing 0.5 M NaCl. Differences in the elution profiles indicated that the RIPs possessed different affinities for the Cibacron Blue F3GA dye. Conjugation of the RIPs to the monoclonal antibody Fib75 resulted in decreased affinity for Blue Sepharose. Under conditions allowing the complete separation of the Fib75-ricin A chain immunotoxin from unconjugated Fib75, the Fib75 immunotoxins made with gelonin and momordin failed to bind completely to the Blue Sepharose column. The Fib75-gelonin and Fib75-momordin fractions that eluted from the column with 0.5 M NaCl were free of unconjugated Fib75 but were enriched in multiply substituted conjugate molecules. A high performance liquid immunoaffinity chromatography procedure based on the selective binding of conjugated RIP to immobilised affinity-purified anti-RIP antibody permitted the complete separation of the gelonin and momordin immunotoxins from unconjugated Fib75 without altering the composition, molecular integrity or cytotoxic activity of the immunotoxins. PMID- 2273255 TI - A novel flow cytometric method for measuring protein digestion within the phagocytic vacuole of polymorphonuclear neutrophils. AB - When rhodamine is attached to albumin at a high molar ratio its fluorescence is quenched but fluorescence is released when the protein is digested and the dye released. Using this observation it is possible to measure protein digestion within the phagocytic vacuole of neutrophils. The assay is simple, rapid and measures digestion even in the presence of abnormal phagocytosis. PMID- 2273256 TI - Antibody response in immunized rabbits measured with bacterial immunoglobulin binding proteins. AB - Protein G, an immunoglobulin (Ig)-binding protein isolated from group C or G streptococci, binds to the Fc portion of IgG. Protein L, from the anaerobic bacterium Peptostreptococcus magnus, specifically binds light chains of Ig. In this study, protein G and L were used to measure the production of antibodies in immunized rabbits. Two rabbits were immunized with a mixture of human urinary proteins from a patient with tubular proteinuria, and blood samples were collected regularly from the animals for 6 weeks after the immunization. The antibody levels of the blood samples against six of the proteins in the antigen mixture were then measured by ELISA. Microtiter plates were coated with each of the antigens, incubated with the rabbit serum samples, and the specific antibodies of the IgG class measured by incubation with biotinylated protein G, and antibodies of all Ig classes with biotinylated protein L. Alternatively, Western blotting was employed, where the antibodies which bound to each antigen after separation by SDS-PAGE and transfer to nitrocellulose membranes, were detected by protein G or L. The results showed that antibody production against five of the antigens, albumin, alpha 1 gamma-acid glycoprotein, alpha 1 gamma microglobulin, Ig light chains, and retinol-binding protein, showed a similar pattern, although the magnitude of the initial IgM response differed somewhat. After 6 weeks, the levels of the protein G-binding antibodies had reached a plateau, while those of protein L-binding antibodies were still increasing. The response to the sixth antigen, beta 2 microglobulin, was considerably different. A dramatic increase of anti-beta 2 gamma-microglobulin antibodies was seen during the 4th week after immunization when protein L was used. PMID- 2273257 TI - A simplified cellular ELISA (CELISA) for the detection of antibodies reacting with cell-surface antigens. AB - This paper describes the adaptation of a cellular enzyme-linked immunosorbent assay (CELISA) for the detection of antibodies to cell-surface antigens. This CELISA has the advantages of convenience and rapidity and is therefore ideally suited for the screening of a large number of hybridoma culture supernatants. The basic procedure involves the direct drying of cell suspensions onto the wells of enzyme immunoassay (EIA) plates and a subsequent EIA with appropriate blocking reagents. In order to overcome high background binding of primary antibodies to Fc receptors and of secondary antibodies to surface Ig (sIg), this method involves a blocking step consisting of unlabelled secondary antibodies. Once CELISA plates are prepared, they can be stored for a period of at least 6 months and hence this assay does not rely on the availability of fresh, viable cells for each assay. This assay is simple, reproducible and sensitive. The results can be assessed in an objective manner and can also be adapted for the detection of cellular antigens. This paper describes a CELISA for the detection of antibodies to blood group antigens and human leukocyte (HLA) antigens. PMID- 2273258 TI - Detection of circulating immune complexes with polyethylene glycol precipitation F(ab')2 anti-C3 ELISA. AB - A polyethylene glycol (PEG) precipitation F(ab')2 anti-C3 ELISA for the detection of complement-fixing IgG circulating immune complexes (CIC) is described. For this assay, test sera were treated with 3.5% PEG and then measured with F(ab')2 anti-C3 ELISA. The lower detection limit was 4 micrograms/ml of heat aggregated human IgG (HAHG). Intra-assay coefficient of variation (CV) was 4.9-8.3%. High levels of CIC are found in the sera of patients with systemic lupus erythematosus (SLE), hepatitis B and stomach cancer. PMID- 2273260 TI - A one-step two-particle latex immunoassay for the detection of Salmonella typhi endotoxin. AB - A simple and rapid test (LIMM, short for latex immunoassay) is described for detecting Salmonella typhi endotoxin. It involves the simultaneous binding of the antigen by two types of reagent particles contained in a micro-tube: an indicator latex particle coated with a monoclonal antibody specific for the O-9 determinant on the endotoxin, and a magnetic bead coated with another monoclonal antibody specific for a different O-determinant. At the end of-the test, the magnetic beads are sedimented by use of a magnet, and the result is read based on the turbidity of the indicator latex suspension. Compared to a similar assay developed previously which uses only a single particle reagent (i.e., a tube agglutination system), LIMM was found to be slightly more sensitive especially when using short (less than 30 min) incubation times, and was at all times easier to read. The sensitivity of LIMM, in fact, increased with increasing time of incubation. When compared to the sensitivity (25 ng/ml) of a conventional slide latex agglutination test performed using the same indicator latex reagent, this parameter was 0-, 4.9-, 12.5- and 28.7-fold better after 5, 15, 30 and 60 min of incubation in the LIMM. PMID- 2273259 TI - Development of a simple, sensitive and specific bioassay for interleukin-1 based on the proliferation of RPMI 1788 cells. Comparison with other bioassays for IL 1. AB - The IL-1-dependent proliferation of RPMI 1788, a human EBV-transformed cell line, was used to develop a biological assay system for IL-1. Preparations of rhIL-1 alpha and rhIL-1 beta, as well as rmIL-1 beta exhibited a specific biological activity (50% of the maximal response) between 5.8 x 10(8) and 8.6 x 10(8) U/mg. Remarkably, a 3-5-fold reduced specific biological activity was noticed for rm-IL 1 alpha, viz. 1.7 x 10(8) U/mg. The IL-1-dependent proliferation of RPMI 1788 cells was compared with other IL-1 test systems, such as the IL-1-mediated induction of IL-2 in EL4-NOB-1, LBRM-33-1A5 and thymocytes, and the IL-1-driven induction of cytotoxic activity by PC60 cells, the so-called CIA assay. The cytokine-dependent growth of RPMI 1788 cells is highly specific for IL-1, and no other cytokine tested induced a proliferative response. The presence of high concentrations of rmTNF, rhTNF or rhIL-6 did not interfere with the quantification of IL-1. Additionally, we evaluated the detection of IL-1 in the presence of mitogens, phorbol ester or calcium ionophore, as well as the determination of IL-1 in serum and PF samples of human and murine origin. PMID- 2273261 TI - An ELISA procedure for the determination of protein G-binding antibodies. PMID- 2273262 TI - The use of tetramethylbenzidine for solid phase immunoassays. AB - A rapid, sensitive, solid-phase immunoassay, using horseradish peroxidase and 3,3',5,5'-tetramethylbenzidine, was found to be more sensitive and the colour developed was more stable compared with HRPO using 4-chloro-1-naphthol or diaminobenzidine. Assay sensitivity was equal to or greater than that obtained with the alkaline phosphatase reaction. The essential step was to incubate filters in 1% dextran sulphate for 10 min in a pH 5 (10 mM citrate-EDTA) buffer before reacting with TMB (0.05 mg/ml in the same buffer). PMID- 2273263 TI - Which method for the assessment of spreading of polymorphonuclear leukocytes? PMID- 2273264 TI - The safety and utility of leukapheresis of normal donors for obtaining products for immunologic research. PMID- 2273265 TI - A heterogeneous immunoassay performed on a rotating carbon disk electrode with electrocatalytic detection. Mass transfer control of the capture of an enterotoxin. AB - An ELISA procedure for the determination of enterotoxin A from Staphylococcus aureus conducted on the surface of a glassy carbon electrode is described. The electrocatalytic detection of the immobilized labelled second antibody is based upon the electrochemical reaction and the enzymatic catalysis occurring on the same surface. The indirect quantification of the bound antigen is, therefore, very sensitive (10(-15) mol cm-2). This heterogeneous technique was used to study the kinetics of antigen binding to the immunological solid phase, the mass transfer of the antigen being controlled under well-defined hydrodynamic conditions. The experiments were performed with a rotating solid phase disk in such a way that thickness of the diffusion layer was known. We found that the capture of the antigen by the immobilized monoclonal antibody was solely limited by diffusion. A simple theoretical model permitted the amount of bound antigen and the sensitivity of the method to be predicted as a function of the incubation time, the rotational speed of the solid phase and the volume of the sample. Both the theory and the experimental results indicate that the assay may be performed with the sample volume undefined. PMID- 2273266 TI - A rapid objective immunofluorescence microassay. Application for detection of surface and intracellular antigens. AB - An indirect immunofluorescence microassay, which permits automated reading, has been employed for simple, rapid and objective detection of surface and intracellular antigens. Initially, the cells, spun in microplates, are fixed with glutaraldehyde (0.25% v/v in PBS). Following fixation, the cells can be stored at 4 degrees C for up to 2 weeks before being used in the immunofluorescence microassay. The fixed cells are then stained according to standard procedures using appropriate first and fluorescein-conjugated second antibodies. An automated and quantitative evaluation of the fluorescence intensity of the cell samples was achieved using the Titertek Fluoroskan II automatic reader. This microassay was shown to be suitable for the detection of the surface MAC1 antigen and intracellular v-myc protein in the GG2EE macrophage cell line. PMID- 2273267 TI - Quantitation of protein A in human plasma is possible after heat inactivation of the samples. AB - Quantitative determination of staphylococcal protein A in plasma is often hampered by the interaction between protein A and immunoglobulins. In human plasma, these interactions may not only involve the non-immune binding to the Fc or Fab regions of Ig but also antigen/antibody interaction by specific antibodies directed against protein A. In this paper we describe a method which can be used to quantitate nanogram amounts of protein A in the presence of human plasma. The ELISA used for the quantification of protein A is based on a double antibody solid-phase assay utilizing chicken anti-protein A as both capture and detector antibody. Protein A may be measured down to 5 ng/ml in plasma and 0.5 ng/ml in buffer. The plasma samples were heat-inactivated before analysis and this eliminated interference in the assay caused by interaction of protein A with an excess of immunoglobulins. This assay provides a reliable and convenient method for the detection and quantitation of soluble protein A in human plasma. PMID- 2273268 TI - A simple and sensitive flow cytometric assay for the determination of the cytotoxic activity of human natural killer cells. AB - A new, simple and sensitive flow cytometric assay for the determination of the cytotoxic activity of human natural killer cells is described. The assay is based on the use of two fluorochromes. The target cell population is stained with one fluorochrome (octadecylamine-fluorescein isothiocyanate, F-18) prior to incubation with the effector cells. F-18 remains in the membrane of the target cells even when they are killed thereby permitting a clear separation between effector and target cells. Dead cells are determined by staining with a second fluorochrome (propidium iodide) after incubation of effector and target cells. staining with a second fluorochrome (propidium iodide) after incubation of effector and target cells. F-18 is not toxic and does not decrease the cytotoxic activity of human natural killer cells. It is also stable (exchange between labeled and non-labeled cells is negligible in a period of at least 4 h at 37 degrees C) and it remains in the membrane of the killed cells. A clear distinction between unlabeled effector and labeled target cells is obtained, even after incubation of target and effector cells for 4 h at 37 degrees C and using a high effector cell-target cell ratio (75:1). A good correlation with the 51Cr release assay was obtained. A potential application of the flow cytometric cytotoxicity assay using whole blood instead of isolated lymphocytes is presented. PMID- 2273269 TI - A tube latex test based on colour separation for the detection of IgM antibodies to either one of two different microorganisms. AB - A simple two stage assay was developed for the detection of IgM antibodies to either one of two microorganisms chosen arbitrarily for this study. Salmonella enteritidis and Trichinella spiralis. In the first stage, magnetic polystyrene beads (Dynabeads) coated with anti-mu (mouse) antibodies were incubated with the test material for 45 min to capture the IgM antibodies. In the second stage, indicator latex particles were incubated with the Dynabeads for 30 min and the results read following settlement of the Dynabeads under the influence of a magnet. Two types of indicator particles were used: blue-coloured (sensitized with Trichinella antigen) and red-coloured (sensitized with Salmonella antigen). These were mixed in suitable proportions to form a purple suspension. Reaction of either type of latex particles due to binding to the adsorbed IgM antibodies resulted in the settlement of that particle and hence a change of colour in the suspension to either red (if Trichinella-specific antibodies alone were present) or blue (if Salmonella-specific antibodies alone were present). When applied to the sera (used at 1/10 dilution) of both normal and immunized mice, the assay was positive for all but one (18) immune sera, and negative for all but one (9) normal sera. PMID- 2273270 TI - Enhanced efficiency of cell hybridization by neuraminidase treatment. AB - Cell hybridization techniques have already been utilized, but the outcome is usually not very stable. In order to achieve high stability we tried to achieve closer intercellular contact. Neuraminidase treatment was used to remove sialic acid from the cell membrane, since sialic acid usually prevents close contact between B cells and myeloma cells. After neuraminidase treatment, not only mouse mouse hybridization but also human-mouse hybridization produced significantly more clones. Our results indicate that neuraminidase treatment is a useful method for generating hybridomas efficiently. PMID- 2273271 TI - Streptococcus zooepidemicus (Lancefield group C) septicaemia in Hong Kong. AB - The clinical findings relating to 11 patients in Hong Kong (HK) and to 43 patients described elsewhere, all with Streptococcus zooepidemicus septicaemia, are reviewed. There was a particular association with cardiovascular disease (27%) with seven cases of endocarditis, three of abdominal aortic aneurysm and two of deep venous thrombosis. Associations not previously reported included two cases of pharyngitis and two patients with persistent post-operative fever. The overall mortality was 22%. Both human and porcine strains of S. zooepidemicus from HK did not hydrolyse aesculin in contrast to the aesculin-positive biotypes reported previously. HK strains also had very mucoid colonies and capsules of hyaluronic acid were seen in electron micrographs. Samples of chromosomal DNA, extracted by means of HindIII restriction endonuclease, of strains from human beings and pigs were identical. The MIC of penicillin for all strains was less than or equal to 0.03 mg/l but the MBC for all was greater than 32 mg/l. Penicillin alone is generally sufficient for cure but combination with an aminoglycoside may be indicated in seriously ill patients. In our locality, pigs were incriminated as a possible source of human infection whereas consumption of contaminated dairy products is important elsewhere. PMID- 2273272 TI - Psittacosis: a clinical review. AB - The records of the Public Health Laboratory at Leeds were searched and cases in which a four-fold rise of antibodies to Chlamydia psittaci had occurred were reviewed. Clinical and epidemiological features of these cases are presented. The importance of birds as a potential source of infection is emphasised. PMID- 2273273 TI - Visceral leishmaniasis in patients infected with human immunodeficiency virus. Co operative Group for the Study of Leishmaniasis in AIDS. AB - We describe 40 HIV-seropositive patients who developed visceral leishmaniasis. All the patients lived in areas endemic for visceral leishmaniasis and belonged to groups at risk for AIDS. Twenty-three patients (57.2%) had definitive AIDS before or after diagnosis of leishmaniasis and 77.5% were classified as belonging to CDC group IV. Fever was present in 95% patients and enlargement of the liver and/or spleen in 92.5%. Lymphopenia was found in 78.3%, depression of the absolute number of CD4 lymphocytes in 90% and depression of the CD4 to CD8 ratio in all evaluated cases but leishmania antibodies were found in only 35.2%. Parasites were demonstrated in the bone marrow or liver in every case. Thirty patients (75%) showed an initial good response to antimonial drugs, although the leishmaniasis followed a chronic or relapsing course in 17 (42.5%). HIV-related mortality was 40%. A significant correlation was found only between the relapsing course of the disease and mortality. In a multivariate linear regression model, the relapsing course was the only variable that influenced mortality. Visceral leishmaniasis is an opportunistic disease that should be suspected in HIV infected patients. We suggest that it should be included in the CDC group IV C-1 and considered as a disease indicative of AIDS. PMID- 2273274 TI - Phenotypic differences and characteristics of pyelonephritogenic strains of Escherichia coli isolated from children and adults. AB - We examined the frequency of bacterial strains expressing cell surface hydrophobicity, P-fimbriae, mannose-resistant haemagglutination (MRHA), type I fimbriae, production of aerobactin, haemolysin synthesis (Hly), production of cytotoxic necrotising factor (CNF) and HeLa cell adherence in 126 strains of Escherichia coli isolated from children (n = 65) and women (n = 61) with acute non-obstructive pyelonephritis. Previous investigations have shown that pyelonephritogenic strains of E. coli more often express hydrophobic properties, P-fimbriae, MRHA, aerobactin-mediated iron uptake, Hly and CNF production than strains isolated from the faecal flora of healthy persons. The objective of the present study was to examine phenotypic differences between strains of E. coli obtained from children with their first episode of acute pyelonephritis and strains from women with non-obstructive acute pyelonephritis. Of the pyelonephritogenic strains of E. coli isolated from children, 98% expressed cell surface hydrophobic properties compared to 82% isolated from adults (P = 0.004). Strains from children and adults had the same ability to assimilate iron and equally often expressed P-fimbriae, MRHA and type I fimbriae. Strains from children with acute pyelonephritis more significantly expressed Hly (72%) and CNF (58%) than did pyelonephritogenic strains from adults (49 and 37% respectively, P = 0.013 and P = 0.028 respectively). The frequency of HeLa cell adherence was similar and low in both groups. The phenotype aerobactin+ Hly+ and Hly+CNF+ was found significantly more often in pyelonephritogenic strains from children than in strains from adults (P = 0.006 and P = 0.028 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273275 TI - Prevalence of Clostridium difficile on a mixed-function ward for the elderly. AB - We studied the prevalence of Clostridium difficile over a period of 2 months on a mixed-function geriatric ward. Seven (14%) of the 49 patients were long-stay but the remainder were in hospital for acute illness or required a short period of active rehabilitation. Although 69% patients had recently received antibiotics, from only two (4%) was C. difficile isolated from their faeces. Our results show that C. difficile is not endemic in patients on all geriatric wards as has been previously suggested. PMID- 2273276 TI - Cryptosporidiosis--an educational experience. AB - Eleven children aged 7 to 8 years from one school class developed diarrhoea and vomiting after an educational visit to a dairy farm. Three required hospital admission and intravenous fluid replacement for dehydration. Cryptosporidium oocytes were found in the faeces of these three children and from one classmate when the remainder of the class was tested between 16 and 21 days after the visit. At the farm some children tasted pelleted cow feed, silage and dried milk powder. A case-control study showed a significant correlation between diarrhoea and the tasting of silage and pelleted feed. Guidance on the safe conduct of educational visits to farms is given. PMID- 2273277 TI - Clinical and serological manifestations in patients during a waterborne epidemic due to Campylobacter jejuni. AB - A clinical and serological investigation of an epidemic due to Campylobacter jejuni in a community with a population of 1026 is presented. Altogether, 22 faecal samples from 27 patients were positive, with serotypes O 2 (n = 21) and O 6, 7 (n = 1) being identified. Serotype O 19, 21 was isolated from drinking water which had been consumed by 89.5% households answering a questionnaire, thereby indicating an attack rate of 66.5% (i.e. 680 persons). Mean duration of illness was 6.5 +/- 4.6 days. Diarrhoea (82.3%), abdominal pains (62.8%) and fever (41.8%) were the most common symptoms. Acute stage samples of serum from Campylobacter-positive patients had lower concentrations of IgG antibodies against the most common serotype (O 2) than against serotype O 6, 7 (P = 0.05), which had previously been implicated in epidemics in the region. More than 80% samples drawn after 1-2 weeks of illness were positive for either IgA, IgM or IgG antibodies to serotype O 2 with a dominance of IgA. In the convalescent group (n = 24), serum from only one patient who developed a long-lasting reactive arthritis had antibodies to all serotypes. PMID- 2273278 TI - Intestinal spirochaetosis in a man with the acquired immune deficiency syndrome (AIDS) PMID- 2273280 TI - Escherichia coli lobar pneumonia. PMID- 2273279 TI - Endocarditis caused by Veillonella dispar. PMID- 2273281 TI - Lactobacillus jensenii prosthetic valve endocarditis. PMID- 2273282 TI - Vaccination and prevention of acute viral hepatitis B in health care workers. PMID- 2273283 TI - Selective inhibition of cecropin-like activity of insect immune blood by protease from American foulbrood scales. AB - Bioassays of American foulbrood larval scale filtrates have shown the presence of an immune inhibitor with a specific activity of proteases that selectively destroy cecropin-like activity in insect immune hemolymphs. It was an unexpected phenomenon to find that Bacillus larvae protease(s), even at trace concentrations, totally inhibits bactericidal activity of immune blood against Escherichia coli D 31. Thermal inactivation of a proteolytic enzyme coincides strictly with a disappearance of the ability to inhibit a cecropin-type activity in an assay system used, although the immune inhibitor was unaffected by trypsin digestion. Since neither bee larval hemolymph nor larval body homogenates possess demonstrable inhibitory action against cecropins present in hemolymph of Celerio euphorbiae and other insects, one can suggest that B. larvae proteases selectively destroy some molecules of the insect humoral immune system. The absence of cecropins in blood of immunized honeybee, Apis mellifera, larvae and a simultaneous high inhibitory activity of B. larvae protease(s) need further study on their role in pathogenesis of American foulbrood of the honeybee. PMID- 2273284 TI - Expression of densonucleosis virus GmDNV in Galleria mellonella larvae: size analysis and in vitro translation of viral transcription products. AB - The RNA of densonucleosis virus type 1 (GmDNV), isolated from GmDNV-infected Galleria mellonella larvae, was shown by Northern blotting to contain five polyadenylated, viral-specific RNA species with sizes of 1.8, 2.4, 3.5, 4.0, and 5.0 kb. Poly(A)-containing RNA from whole larvae and hybrid-selected viral RNA were translated in a rabbit reticulocyte lysate system and the translation products were coelectrophoresed with proteins extracted from CsCl-purified virus. All four virion-associated proteins, namely p49, p55, p65, and p94, were present in the in vitro-translated products. However, in the majority of the experiments the most abundant translation product was a 30K polypeptide which is absent from virion extracts. The most abundant viral protein is p49, and the 49K polypeptide was also the most abundant translation product in about 30% of the preparations. The 1.8 kb transcript, which constitutes about half of the total viral RNA, is only slightly larger than the template required for a 30K polypeptide, suggesting that the latter may be a primary translation product of the smallest RNA transcript. The similarities in gene expression between densoviruses and mam malian parvoviruses are discussed. PMID- 2273285 TI - Fine structural observations of the granulocytes involved in the tunic inflammatory-like reaction of Ciona intestinalis (Tunicata). AB - Erythrocytes injected into the tunic of Ciona intestinalis induced an inflammatory-like reaction which can cause lysis of the neighboring tissue. Electron microscopy observations of the granulocytes of the injured tunic show lysosomic figures and degranulations features suggesting granulocyte involvement in the destructive process. PMID- 2273286 TI - Antibacterial activity in the hemolymph of myriapods (Arthropoda). AB - The hemolymphs of two diplopod (Chicobolus sp. and Rhapidostreptus virgator) and two chilopod species (Lithobius forficatus and Scolopendra cingulata) were tested for the presence of antibacterial substances using Petri dish tests. The native hemolymph of all species had substances acting on living Micrococcus luteus, whereas only Rhapidostreptus, Scolopendra, and Lithobius were effective against lyophilized Micrococcus. The antibacterial activity against living Micrococcus increased after inoculation with bacteria (Enterobacter cloacae beta-12) in Chicobolus and Rhapidostreptus and also against lyophilized Micrococcus in the latter. Thus, these effects appear to be inducible. None of the myriapods tested had any bacteriostatic effect on Escherichia coli D-31 whereas the growth of gram negative E. cloacae was inhibited. The antibacterial substances in the diplopod species were unstable when heated but were resistant to freezing. At least two antibacterial substances (a lysozyme-like one and another substance) are considered to occur in Myriapoda. PMID- 2273287 TI - Crystals of virus-like particles in the metacestodes of Taenia solium and T. crassiceps. AB - Crystals of virus-like particles (VLP) are described as occurring in the nuclei of damaged tegumentary cytons from carcasses of Taenia solium metacestodes that had been stripped of their teguments. The VLP are grouped as parallel lines of round particles in an hexagonal packaging of spheroids forming small or large crystals. The individual particles have an external diameter of 36-37 nm and a wall of 5-6 nm thick, which surround a cavity of lower electron density. As identical crystals were also observed in normal tissues of T. solium and of T. crassiceps, it is suggested that both species of cysticerci are normal carriers of a similar species of virus. The possible biological implications of this condition are discussed. PMID- 2273288 TI - Replication of an entomopoxvirus in two lepidopteran cell lines. AB - Pseudaletia separata entomopoxvirus replicated in two lepidopteran cell lines, SIE-MSH-805-F and BM-N. Microscopic examination, and the virus passage tests, of infected cultures indicated that the virus replicated more readily in the former cell line. Virus release by exocytosis occurred in both cell lines. A sequence of virus morphogenesis in the cultured cells was described, based on electron microscopic observations of thin sections. The nucleus of infected cells contained spherical inclusions, and the cytoplasm contained virions, immature virus forms, spheroids, and spindles. A portion of the virions in the cytoplasm was occluded within spheroids, which were often associated with crystallogenic matrix. Virions acquired a coat prior to their occlusion. PMID- 2273289 TI - Activation and germination of Bacillus thuringiensis spores in Manduca sexta larval gut fluid. AB - Incubation of Bacillus thuringiensis HD-1 spores in the larval gut fluid of Manduca sexta (tobacco hornworm) resulted in increased viable counts, conversion to phase-dark spores, and a loss of absorbance in spore suspensions, indicative of spore germination. Heat-activated and untreated spores incubated in water did not exhibit these changes. Only when spores were heat activated and incubated in germinants L-alanine and adenosine did changes in the spores approximate those observed in gut fluid. These data suggest that M. sexta larval gut fluid induces the activation and germination of B. thuringiensis spores. PMID- 2273290 TI - Specificity and efficacy of purified Bacillus thuringiensis proteins against agronomically important insects. AB - The host range and relative efficacy of three purified Bacillus thuringiensis insect control proteins were determined against 17 different agronomically important insects representing five orders and one species of mite. The three B. thuringiensis proteins were single gene products from B. thuringiensis ssp. kurstaki HD-1 (CryIA(b)) and HD-73 (CryIA(c)), both lepidopteran-specific proteins, and B. thuringiensis ssp. tenebrionis (CryIIIA), a coleopteran-specific protein. Seven insects showed sensitivity to both B. thuringiensis ssp. kurstaki proteins, whereas only 1 of the 18 insects was sensitive to B. thuringiensis ssp. tenebrionis protein. The level of B. thuringiensis ssp. kurstaki protein required for 50% mortality (LC50) varied by 2000-fold for these 7 insects. A larval growth inhibition assay was developed to determine the amount of B. thuringiensis ssp. kurstaki protein required to inhibit larval growth by 50% (EC50). This extremely sensitive assay enabled detection of B. thuringiensis ssp. kurstaki HD-73 levels as low as 1 ng/ml. PMID- 2273291 TI - High-pressure liquid chromatographic analysis of hemolymph plasma catecholamines in immune-reactive Aedes aegypti. AB - Tyrosine and catecholamines have been implicated as substrates for the encapsulation reactions involved in the immune response of mosquitoes to microfilariae (mff). Identification and quantitation of tyrosine and catecholamines present in Aedes aegypti hemolymph plasma were accomplished by ion pair high-pressure liquid chromatography with electrochemical detection at either +650 or +850 mV vs Ag/AgCl. Tyrosine, dopamine, and N-beta-alanyldopamine were detected in the hemolymph plasma of naive A. aegypti. Although no differences in these compounds were observed in hemolymph plasma from A. aegypti inoculated with Dirofilaria immitis mff, the chromatogram showed a single major peak (PI) (65 microM, expressed as dopamine equivalents) that was not present in naive hemolymph plasma. Saline-inoculated controls contained only 5% of the PI in immune reactive hemolymph plasma. A high concentration of PI (127 +/- 39 microM) was also detected after treatment of hemolymph plasma with mild alkaline conditions (pH 9.0), indicating that it is normally present as an electrochemically inert form in naive mosquitoes. High concentrations of PI were also detected in the naive hemolymph plasma from three other mosquito species, but no PI was found in A. trivittatus under any conditions. PI did not cochromatograph with any of the catecholamines commonly thought to be involved in immune responses of dipterans against metazoan parasites, suggesting that it may be a unique substrate for these reactions. The biological relevance of PI was evidenced by its appearance in the hemolymph plasma of two strains of D. immitis inoculated A. aegypti. PMID- 2273292 TI - Bacillus thuringiensis subspecies neoleonensis serotype H-24, a new subspecies which produces a triangular crystal. PMID- 2273293 TI - Plasmids in Bacillus popilliae. PMID- 2273294 TI - Cancer centers and cancer research: the need for recognition and increased funding. PMID- 2273295 TI - Several types of adherent cells elaborate a dialyzable lymphopoietic cofactor (Abelson Growth Promoter). AB - We have cloned a stromal cell from mouse bone marrow selected on the basis of its ability to promote the growth of an Abelson virus-transformed pre-B cell line. These stromal cells have smooth muscle features, and the ultrafiltrate of stromal cell-conditioned medium has proliferative effects on all feeder layer-responsive mouse pre-B cell lines tested, as well as on normal pre-B cells. One of these low MW substances is a protease-resistant factor with an MW of approximately 450 Da which we designate Abelson Growth Promoter (AGP). AGP was initially characterized as an activity which promotes the growth of Abelson virus-transformed mouse pre-B cells, but it also promotes the growth of a ras-transformed pre-B cell line as a single agent and in synergistic fashion with recombinant interleukin (IL) 7. AGP as a single agent has no effect on normal pre-B cells, which have a brisk response to IL-7. In contrast, transformed pre-B cells display a blunted response to IL-7. We propose that AGP plays a role in normal lymphopoiesis by expanding clones of pre-B cells which have been activated by other stromal cell-derived signals, such as IL-7, and directly promotes the growth of nascently transformed pre-B cells. PMID- 2273296 TI - Hematopoiesis on cellulose ester membranes (CEM). XII. Effect of membrane enrichment by purified matrix proteins. AB - Cellulose ester membranes (CEM) were enriched with the following purified matrix proteins: collagen I, II, IV, proteoglycan and laminin. Fifteen milligrams of each were placed on CEM which were then folded into open-ended tubes implanted i.p. and s.c. CEM were removed after 3, 6 and 12 months and examined histologically. There was no evidence of hematopoiesis or new bone formation on the implanted, enriched CEM at any of the intervals examined. Collagen I and proteoglycan-enriched CEM showed evidence of increased sinusoid-like vascular structures. PMID- 2273297 TI - Selectivity of hemoregulatory peptide (HP5b) action in culture. AB - A synthetic analog of a hemoregulatory peptide associated with mature human granulocytes (HP5b) has been investigated for inhibitory effects on various cell types in culture as compared to inhibitory action on mouse and human myelopoietic colonies (CFU-gm), which occurs from 1 X 10(-13) to 1 X 10(-6) M in vitro. This includes colony formation by lymphoid T and B cells in capillary cultures, as well as mitogen activation of T, B and NK cells. At higher concentrations, i.e., above 1 X 10(-7) M, an inhibitory effect was found on colony formation. Neither the production of interleukin (IL) 3 by mitogen-activated T cells, nor the proliferation of the IL-3-dependent L/B cell line were affected by the peptide up to 1 X 10(-5) M. A slight inhibitory effect was found above 1 X 10(-9) M on mouse 3T3 fibroblasts. A series of malignant cell lines was also tested. No effect was seen between 1 X 10(-11) and 1 X 10(-7) M on human mammary carcinoma cells in culture. On Ehrlich ascites mouse mammary carcinoma cells a 30% inhibition was seen at 10(-6) M. On a human glioblastoma cell line (GaMg) no effect was seen, and on a rat glioma cell line (BT5C) an inhibitory effect was seen at 1 X 10(-7) M and above. No significant inhibition of cell growth was seen on SC1 mouse lymphoma cells from 1 X 10(-9) to 1 X 10(-5) M during 7 days of culture. The investigated normal and malignant cell types in culture were thus not inhibited in very low concentrations which act on CFU-gm. However, a variable inhibitory effect was found at higher concentrations where the inhibition of myelopoiesis was maximal and at concentrations where the inhibition is released. The hemoregulatory peptide thus seems to be a concentration-dependent selective inhibitor of myelopoiesis. The finding that various malignant cells do not respond at lower concentrations supports the possibility of using the peptide as a protector of normal cells during cancer chemotherapy. PMID- 2273298 TI - Improvement of anemia by recombinant erythropoietin in patients with myelodysplastic syndromes and aplastic anemia. AB - Eight patients with myelodysplastic syndromes (MDS) and four patients with aplastic anemia (AA) were treated with recombinant erythropoietin (rEpo) to investigate its effect on the anemia of these patients. rEpo was administered by i.v. injection three times a week for at least four weeks. The doses were 3,000, 6,000, or 12,000 U/day. Despite an elevated "endogenous" Epo level, a greater than 1.5 g/dl increase in hemoglobin (Hb) concentration was observed in one patient with refractory anemia (RA), one patient with refractory anemia with excess of blasts (RAEB), and one patient with AA. A greater than 50% decrease in red cell transfusion requirement was observed in one patient with RA and one patient with AA. One RA patient and one AA patient have received rEpo as maintenance therapy for more than 64 and 100 weeks, respectively. They no longer need red cell transfusions and have had a normal Hb concentration and normal ferrokinetics. No side effect was seen. These results indicate that rEpo may benefit some patients with MDS and AA who are dependent on red cell transfusions while further studies will be necessary to elucidate the mechanism by which rEpo stimulates erythropoiesis and improves anemia in patients with these diseases. PMID- 2273299 TI - Phase II evaluation of recombinant interferon-beta (IFN-beta ser) in patients with diffuse mesothelioma: a Southwest Oncology Group study. AB - Fourteen evaluable patients with diffuse malignant mesothelioma were treated with a once-a-day for 5 days out of 7 for 6 weeks regimen of recombinant interferon beta (IFN-beta ser). No responses were noted. The major toxicities included fever, chills, nausea, vomiting, and anorexia. IFN-beta ser at this dose and schedule does not appear to be an active single agent for patients with refractory malignant mesothelioma. PMID- 2273300 TI - Combined effects of interferon and 2'-deoxycoformycin on 2',5'-oligoadenylate synthetase and adenosine deaminase in hairy cell and chronic lymphocytic leukemia cells. AB - The combined effects of interferon (IFN) and 2'-deoxycoformycin (DCF) on 2',5' oligoadenylate (2-5A) synthetase and adenosine deaminase (ADA) activity were examined in vitro in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL). In HCL cells, the effects of IFN and DCF on both OAS and ADA activity were strictly antagonistic. Antagonism in inducing OAS activity was also observed in CLL cells, although, in general, little interaction between DCF and IFN occurred in these cells. If OAS and ADA are important in the antitumor effects of IFN and DCF, our results suggest that combination therapy with IFN and DCF could be counterproductive. PMID- 2273301 TI - [The effect of endogenous tumor necrosis factor (TNF)-induction therapy in the model of VX-2 ovarian carcinoma in the rabbit]. AB - The rabbit ovarian carcinoma model was prepared by injecting VX-2 carcinoma into the ovary and the effects of endogenous Tumor Necrosis Factor (TNF)-induction therapy in combination with chemotherapy were studied. In this model, carcinoma metastasizes easily to the abdominal cavity, lung and liver, and resists treatment. Endogenous TNF was induced by a series of injections of OK-432 0.3KE and OK-432 3KE at 3 hour intervals (OK-OK group), or 1 x 10(10) cells of Bordetella pertussis vaccine (BPV group). Another group were sequential given a series of injections of CDDP (2mg/kg) intraperitoneally and OK-432 intravenously (an OK-OK and CDDP group). Higher activity of endogenous TNF was induced by BPV in comparison with OK-OK plus OK-OK and CDDP. Obvious hemorrhagic necrosis was observed in the implanted ovary in the BPV group. Compared with the control group, pulmonary metastasis was seen in the OK-OK and OK-OK plus CDDP groups (partial remission). These results show that the endogenous TNF induction therapy could be expected to be an effective antitumor therapy for advanced ovarian cancer. PMID- 2273302 TI - [The diminishing oocyte toxicity following intraperitoneal infusion of cisplatin (CDDP) combined with subcutaneous injection of sodium thiosulfate (STS) in syngeneic young mice]. AB - Small oocytes in 6-week-old C57BL/6 mice were destroyed in a dose-dependent fashion following intraperitoneal infusion of CDDP. ED65, the effective dose of which theoretically produced 65% destruction of small oocytes according to Probit analysis, was determined as 0.2mg/mouse. In this study, the oocyte toxicity induced with intraperitoneal treatment with CDDP (0.2mg) was offset by subcutaneous treatment with STS (40mg, 400 x molar ratio compared to that of CDDP). STS was subcutaneously injected into the back skin of mice at 60, 30, 15 minutes before, at the same time or at 15, 30, 60 minutes after the CDDP injection. STS markedly diminished the oocyte toxicity and reduced oocyte destruction about 45% when it was injected at 30, 15 minutes before or at the same time as CDDP infusion. On the other hand STS failed to reduce oocyte destruction when it was injected 15, 30 or 60 minutes later. STS might neutralize CDDP in the circulating blood to decrease the amount of active CDDP, but STS might not have any effect on CDDP once it is incorporated and conjugated with the DNA in the oocytes. PMID- 2273303 TI - [Clinico-pathologic evaluation of retroperitoneal lymph node metastasis in ovarian carcinoma]. AB - Retroperitoneal lymph node dissection was performed in 18 cases of ovarian carcinoma. Of 18 patients, 8 (44.4%) patients had lymph node metastasis. It was found that 50.0% of patients with stage III and 100% of patients with stage IV had lymph node metastasis. Serous cystadenocarcinoma and poorly differentiated carcinoma were demonstrated to be the risk factors in lymph node metastasis. Lymph node metastasis was found to be significantly correlated with the volume of ascites, peritoneal cytology, or peritoneal dissemination. Patients without peritoneal dissemination or positive peritoneal cytology had no lymph node metastasis. Patients with bilateral ovarian tumors tended to have a higher incidence of lymph node metastasis than those with a unilateral ovarian tumor. The incidence of para-aortic lymph node metastasis was found to be higher than that of pelvic or inguinal lymph node metastasis. We concluded that in the clinical stage, serous cystadenocarcinoma, poorly differentiated epithelial carcinoma, ascites, peritoneal cytology, peritoneal dissemination and bilateral ovarian tumors were assumed to affect the incidence of retroperitoneal lymph node metastasis of ovarian carcinoma. It was suspected that the lymphatic spread of ovarian carcinoma had two routes: via ascites and peritoneal dissemination. PMID- 2273304 TI - [Neurobehavior and mental development of newborn infants delivered under epidural analgesia with bupivacaine]. AB - The neurobehavior of newborn infants delivered under epidural analgesia with bupivacaine was analyzed by Amiel-Tison's Neurological and Adaptive Capacity Score (NACS), while Tsumori-Image's questionnaire assessed the above infants' mental development. Seventy-two newborn infants under epidural analgesia (39 delivered spontaneously and 33 by vacuum extraction) and twenty-eight newborn infants without epidural analgesia as controls (15 delivered spontaneously and 13 by vacuum extraction) were under study. The following results were obtained 1) In the 24 hour period following childbirth, NACS tended to be low in relation to the total dosage of bupivacaine administered to the mother. 2) In the 24 hour period following childbirth and continuing until the 3rd day, NACS were relatively low regardless of the mode of delivery. 3) There was no significant difference between the neonatal physiological weight loss in newborn infants under epidural analgesia and those without epidural analgesia (controls). 4) Newborn infants under epidural analgesia displayed an average mental quotient at the first, third, and sixth month after childbirth. Although epidural analgesia with bupivacaine might lower the neurobehavior of newborn infants in the immediate postchildbirth period, the newborn infants should return to normal without any complications. PMID- 2273305 TI - [Collagen and acid glycosaminoglycans in bovine tunica albuginea during ovulatory cycle]. AB - Collagen and acid glycosaminoglycans (GAG) in bovine tunica albuginea covering the developing follicules (FC) and corpus luteum (CL) were investigated histochemically and biochemically in order to analyze the connective tissue metabolism of the follicular wall as well as to clarify the mechanism involved in stigma repairs after ovulation at the extracellular matrix level. Histochemically, collagen fibers were observed to be loose and sparse by Azan Mallory staining and GAG were markedly stained by alucian blue in large FC. Biochemically, hydroxyproline content showed a significant decrease (43%) in large FC compared with control tunica albuginea. Uronic acid and hexosamine content tended to increase in large FC, compared with small FC. The major GAG component in FC was sulfate GAG, consisting mainly of dermatan sulfate (DS). The DS component ratio and concentration were decreased significantly in large FC, compared with small FC. Remodelling of collagen fibers and an increase in GAG content were observed in CL. The increase in GAG content was caused by a threefold increase in the component ratio and concentration of hyaluronic acid in CL, compared with other tunica albuginea. These results suggest that changes in GAG components in FC and CL are strongly related to collagen metabolism in tunica albuginea during the ovulatory cycle. PMID- 2273306 TI - [Rheological analysis of suppressed leukocytosis in patients with pregnancy induced hypertension (PIH)]. AB - It is documented that the number of leukocytes in peripheral blood increases considerably during pregnancy. We observed that the range of leukocytosis differs in normal pregnancy differs from that in cases with severe pregnancy induced hypertension (PIH). The data obtained in our university hospital, for example, give the number of leukocytes after twenty-four weeks of gestation as 9,000 +/- 1,600/mm3 (mean +/- SD) for normal cases (93 measurements in 37 cases) and 6,600 +/- 1,100/mm3 for PIH (72 measurements in 18 cases; p less than 0.001). To elucidate the cause and relation to PIH, we studied changes in the activity of leukocytes during pregnancy by means of a modified Nuclepore filtration method (Kikuchi et al., 1983). The time required for leukocytes to squeeze through filter pores under constant suction varies greatly depending on their active states; more active cells show greater resistance to pore passage, which can be clearly shown by exposing cells to various stimuli. The filtration time for 0.5ml blood containing 5,000/mm3 leukocytes minus that of leukocyte poor blood with the same hematocrit was taken as an index of the activity, which we called the rheological activity of leukocytes (RAL). RAL values for blood taken at delivery were 3.4 +/- 1.5 sec for normal cases and 5.0 +/- 2.1 sec for PIH (N.S.). RAL values obtained after the addition of a chemotactic stimulant FMLP (formyl methionyl-leucyl-phenylalanine) (10nM) to the same samples were 21 +/- 10 sec for normal cases and 405 +/- 265 sec for PIH (p less than 0.001). Leukocyte activity, particularly, response to chemotactic stimulation, was the before thought to be considerably increased in PIH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273307 TI - [The maintenance of placental circulation--the study on the platelet inhibition activity of placental chorioepithelial brush border membrane]. AB - We studied the platelet aggregation inhibiting activity of human placental syncytiotrophoblast brush border membrane vesicles (BBMV) and obtained the following results. 1. There existed a very strong platelet aggregation inhibiting activity in placental BBMV. The BBMV almost completely inhibited the platelet aggregation induced by ADP, arachidonic acid and ristocetin. 2. There existed a very strong ADP degrading activity (ADPase activity) in the placental BBMV. ADP was quickly decomposed to AMP by BBMV. 3. Placental BBMV inhibited platelet TXA2 (TXB2) production. In the 0.04 mg/ml protein concentration of BBMV, platelet TXA2 production was almost completely inhibited. 4. There existed a very strong platelet aggregation inhibiting activity in solved BBMV. Soluble BBMV almost completely inhibited the platelet aggregation induced by ADP and arachidonic acid but did not inhibit the platelet aggregation induced by ristocetin. 5. ADP decomposing activity and platelet TXA2 production inhibiting activity were separated by anion exchange column chromatography of soluble BBMV. 6. When BBMV was treated with ultrasonic waves to destroy the membrane structure, only the activity inhibiting ristocetin-induced platelet aggregation was markedly decreased. PMID- 2273308 TI - [Ultrasonographic changes in the endometrium during ovulatory cycles--correlation to serum estradiol and progesterone concentrations]. AB - Daily changes in the thickness and texture of the endometrium were assessed by ultrasonography in 15 natural ovulatory cycles. The endometrium in the follicular phase became thicker every day until ovulation [5.8 +/- 1.8 mm (mean +/- SD) on day -8, 10.7 +/- 2.9 mm on day 0, day 0: ovulation], but the thickness did not change during the luteal phase. There was a significant correlation between the thickness of the endometrium and the serum estradiol concentration in the follicular phase (r = 0.64, n = 89, p less than 0.01), but the change in the thickness of the endometrium varied with the individual. The texture of the endometrium changed in the menstrual cycle. The hyperechoic area of the endometrium spread from the basal layer to the lumen during the early-mid luteal phase. The ratio of the thickness of the hyperechoic area to the total thickness of the endometrium (hyperechoic endometrial area ratio, HEA ratio) increased from 34.3 +/- 11.0% on day 0 to 100% on day 9. There was a significant correlation between the HEA ratio and the serum progesterone concentration in the period from day -2 to day 9 (r = 0.68, n = 91, p less than 0.01). PMID- 2273309 TI - [The clinical significance of serum sialyl Tn antigen levels in patients with gynecologic tumors]. AB - In order to estimate the clinical significance of sialyl Tn (STN) antigen, the antigen was measured with an "STN" Otsuka Kit in sera from patients with various gynecologic tumors and healthy women. The antigen in ovarian fluid was also determined. Furthermore, the amount of serum STN antigen was serially checked in the patients with increased serum STN to evaluate the correlation between serum STN and the response to treatment. Results obtained were as follows. 1) Among the patients with uterine myoma, uterine malignancies and benign ovarian tumors, the incidence of increased serum STN antigen was low. 2) Among the patients with ovarian malignancies, serum STN antigen was significantly increased in the following order: Clinical stage I (18%) stage II (22%) stage III (68%). 3) The highest STN value was observed in the cyst fluid from ovarian malignancies. 4) The serum STN concentration was correlated with the effect of treatment. Interestingly, the increase in serum STN preceded the clinical detection of recurrence in one case. Thus STN appears to be a useful marker for monitoring ovarian malignancies. PMID- 2273310 TI - [A statistical study of the countermeasures to reduce the maternal mortality based on the relationship between the maternal mortality rate and perinatal mortality rate]. AB - Although both the Japanese maternal mortality rate (MMR) and the perinatal mortality rate (PMR) have decreased remarkably in recent decades, the former is still high compared with other advanced countries. A statistical analysis on the relationship between the MMR and the PMR was performed to investigate this discrepancy. During the period of study, both rates fell by over 50 percent. There were definite statistical differences among the PMR for each prefecture but almost none among the MMR. The prefectures with high PMR remained generally high in the PMR and the prefectures with low PMR also remained low in the MMR. There was no significant correlation between the PMR and the MMR. Both maternal and perinatal deaths due to common causes decreased in number, and there were few regional differences concerning effective measures against them. The leading causes of maternal death which are irrelevant to perinatal death are emboli, bleeding, and some other rare medical complications. Emphasis should therefore be laid upon the early diagnosis and treatment of amniotic fluid embolism apart from measures against haemorrhage. Countermeasures for rare complications are also of great importance. PMID- 2273311 TI - [Intravaginal bacterial flora in patients with uterine cervical cancer, with special reference to Gardnerella vaginalis]. AB - In a total of 18 subjects, comprising 16 cases of uterine cervical cancer (4 cases, stage Ib; 1 case, stage IIa; 11 cases, stage IIb) and 2 cases of cervical dysplasia, the intravaginal bacterial floras, including Gardnerella vaginalis (G. vaginalis) and Mobiluncus spp., were investigated. In uterine cervical cancer, there were mixed bacterial flora of aerobes and anaerobes but what is of note is that G. vaginalis was detected in 7 out of 16 cases of uterine cervical cancer and in 1 out of 2 cases of dysplasia. The number of G. vaginalis present was far greater than that of the other coexisting species. In contrast, none of the Mobiluncus spp. was detected. Since G. vaginalis was detected at a high incidence in uterine cervical cancer and dysplasia, the possibility of a relationship between G. vaginalis and uterine cervical cancer was suggested. PMID- 2273312 TI - [Blood coagulation and fibrinolytic studies in patients with toxemia of pregnancy]. AB - In this study, blood coagulation and fibrinolytic parameters were measured in maternal blood and fetal umbilical cord blood in 200 normal pregnant women and in 46 with severe toxemia of pregnancy (Toxemia), and the relationships between fetal growth and concentrations protein C (PC), antithrombin-III (AT-III) and alpha 2-plasmin inhibitor (alpha 2-PI) were studied. 1. Significant increases in fibrin degradation products (FDP) and in plasminogen (Plg), AT-III and PC were found in maternal blood of Toxemia. A significant increase in AT-III and a decrease in alpha 2-PI and PC were observed in cord blood from these patients. 2. The platelet count (Pl) tended to be low in patients with Toxemia complicated by fetal growth retardation (IUGR). 3. Pl and fibrinogen (Fib) tended to be high in Toxemia complicated by normal fetal growth. 4. PC increased from early pregnancy, and a further increase was observed in the puerperium. 5. The PC concentration correlated with the AT-III but not with the alpha 2-PI concentration in maternal blood. 6. PC in cord blood was lower than that in maternal blood, and was correlated with AT-III and alpha 2-PI. 7. In patients with Toxemia, PC was reduced in both maternal and cord blood, and this correlated with AT-III as well as alpha 2-PI in maternal blood. 8. PC was low in Toxemia complicated by hypertension and proteinuria. These results suggest the involvement of FDP, AT III, PC and Plg in the pathogenesis of Toxemia, and that the Pl, Fib, FDP and alpha 2-PI concentrations are related to fetal growth. Therefore, the PC and AT III concentrations appeared to be a useful index for the blood coagulation and fibrinolysis in pregnant women and appeared to be important factors in the degree of Toxemia and IUGR. PMID- 2273313 TI - A sensitive assay for anti-phosphatidylethanol-amine antibody in patients with recurrent fetal loss. AB - There is strong evidence that anti-phospholipid antibodies is implicated in thrombosis and recurrent fetal death. In recent years, it has been suggested that anti-phosphatidylethanolamine (PE) antibody is an important antibody of this type. In the present study, we established a sensitive enzyme linked immunosorbent assay (ELISA) to detect anti-PE antibodies and examined the relationship between the anti-PE antibody level in serum and recurrent abortion. The improvement of the assay was made by treating PE with 1.0% acetic acid in methanol solution prior to its application to the microplates. This treatment markedly increased the antigenicity of PE. Using this modified ELISA, anti-PE antibodies in 10 patients with a history of recurrent fetal loss were measured before and after therapy during the last period of their pregnancies. IgG anti-PE antibodies were detected in all 10 patients. Four patients exhibiting high titers of IgG anti-PE antibody experienced subsequent intrauterine fetal death (IUFD), while the other 6 patients, whose titers of IgG anti-PE antibody had decreased with therapy, had live births. These results suggest that this modified ELISA for estimating IgG anti-PE antibody is a valuable tool for the diagnosis and prognosis of patients with recurrent fetal loss. PMID- 2273314 TI - [A case of melanosis ovarii et peritonei]. PMID- 2273315 TI - [A case of post-partum eclampsia followed by magnetic resonance imaging and electroencephalography]. PMID- 2273316 TI - [A case of metaplastic Brenner tumor with elevated serum CA19-9 levels]. PMID- 2273317 TI - [Clinical study of congenital obstructive uropathies: prenatal management and prognosis]. PMID- 2273318 TI - [A familial case of oral-facial-digital syndrome]. PMID- 2273319 TI - [Successful tubal anastomosis utilizing contralateral tubal segment in a case of unicornous uterus with a rudimentary horn]. PMID- 2273320 TI - [Proximal displacement of the femoral head after Chiari pelvic osteotomy for coxarthrosis with dysplastic acetabulum]. AB - Proximal displacement of the femoral head can been seen sometimes after Chiari pelvic osteotomy. In order to clarify the causes of the displacement, a quantification analysis was performed to evaluate the factors of this osteotomy. The statistical analysis showed that 54% of the causes could be explained as being due to the angle of osteotomy, obesity ratio, the variation of the acetabular trochanteric distance, and other three factors. Paying attention to get good results: 1) making the angle of osteotomy from 11 degrees to 20 degrees, 2) keeping the variation of the acetabular trochanteric distance within 20mm, 3) the improvement of the lever arm ratio within 15%, and 4) the approximate acetabular index above 30%. In a case with the greater trochanter pulled down, a computer simulation showed that the centripetal force of the femoral head was decreased, and the displacement was increased. PMID- 2273321 TI - [A study of vascular changes on disintegration and repair of the femoral head with advanced osteoarthritis of the hip]. AB - Microangiography was performed on 65 femoral heads with advanced osteoarthritis to investigate the vascular changes on disintegration and repair of the femoral head. Affected femoral heads were removed during prosthetic replacement. A needle was inserted into the nutrient vessel of the extraosseous area and the contrast medium was injected by manual pressure through the needle. After slicing the femoral head, decalcification was performed and Spalteholz's preparations were prepared. Anastomosis between the superior and inferior retinacular arteries was found in all cases. Hypertrophy and hypervascularity of the retinacular arteries were observed on the weight bearing region. On the cystic lesion corresponding to the weight bearing region, numerous arteries were extended around the cyst. On the surface of the eburnated femoral head, the peripheral arteries coursing to the joint was not tapered and dilatation of these arteries was demonstrated. On some areas of the head, however, repairing arteries reaching to the joint surface lay horizontally. From this result, it was assumed that numerous arteries proliferated to the eburnated area and to around the cyst for repairing reaction, but that these were damaged by mechanical stress. PMID- 2273322 TI - [Experimental study on carbon fiber reinforced plastic plate--analysis of stabilizing force required for plate]. AB - Plates currently in use for the management of bone fracture made of metal present with various problems. We manufactured carbon fiber reinforced plastic (CFRP) plates from Pyrofil T/530 puriplegs overlaid at cross angles of +/- 10 degrees, +/- 20 degrees, and +/- 30 degrees for trial and carried out an experimental study on rabbit tibiofibular bones using 316L stainless steel plates of comparable shape and size as controls. The results indicate the influence of CFRP plate upon cortical bone was milder than that of stainless steel plate, with an adequate stabilizing force for the repair of fractured rabbit tibiofibular bones. CFRP has the advantages over metals of being virtually free from corrosion and fatigue, reasonably radiolucent and able to meet a wide range of mechanical requirements. This would make CFRP plate quite promising as a new devices of treating fracture of bones. PMID- 2273324 TI - [Diagnosis and treatment of ligamentous injuries of the ankle]. PMID- 2273323 TI - The role of cartilage canals: experimental study using rabbits' femoral heads. AB - The role of the cartilage canals of the epiphysis was investigated by studying the process of initial enchondral osteogenesis of the secondary ossification center using decapitated femoral heads of one day old Japanese rabbits. Specimens of decapitated femoral heads returned to the original acetabulum demonstrated granulation tissue invasion at ten days after birth, followed by the normal process of enchondral osteogenesis of the secondary ossification centers. In contrast, specimens of heads inserted in the peritoneal cavity to prevent invasion of granulation tissue showed no enchondral osteogenesis of the secondary ossification center, and the major portion of the decapitated femoral head was replaced by necrotic chondrocytes and empty lacunae. The results of this study confirm that the cartilage canal is important not only in the nutrition of the chondroepiphysis but also in the initial enchondral osteogenesis of the secondary ossification center. PMID- 2273325 TI - [Cancer and steroid hormones]. PMID- 2273326 TI - Death associated with abuse of a "designer drug". AB - A case of death is reported in a 26-year-old male previously thought to be healthy. At autopsy, the anterior descending branch of the left coronary artery was markedly atherosclerotic with a superimposed thrombus. Toxicologic analysis revealed 3,4 methylene dioxyamphetamine (MDA) in the blood at a concentration of 0.08 mg per deciliter. The authors draw attention to the reappearance of designer drugs in Kentucky and to the need for awareness of these deadly substance. PMID- 2273327 TI - The presentation and treatment of acute cocaine intoxication: experience of a teaching hospital. AB - With the use of cocaine now at epidemic proportions, primary care physicians have a reasonable probability of having to provide medical care for a cocaine abuser. Because the cocaine reaction may progress rapidly to a fatal outcome, it is essential to know how to recognize and manage the symptoms of cocaine overdose. PMID- 2273328 TI - Clinical study of keratoconus in central Kentucky. AB - Keratoconus is an ectatic corneal disorder that results in a central or inferior conelike anterior protrusion. This results in irregular myopic astigmatism, causing considerable visual impairment. We have completed a retrospective clinical study of keratoconus in the central Kentucky area. When compared to other national studies of keratoconus, our study patients generally had more severe disease at the time of diagnosis and had a higher rate of keratoplasty. Keratoconus treatment is highly successful, and early diagnosis is warranted to prevent unnecessary visual loss. PMID- 2273329 TI - Psychosocial aspects of Alzheimer's disease. AB - November is national Alzheimer's disease month. This disorder involves not only cognitive dysfunction but also psychiatric symptoms. Alzheimer's disease places a tremendous burden on caregivers. These psychosocial factors are often the causes of institutionalization. PMID- 2273330 TI - A radiographic study of sacral base, sacrovertebral, and lumbosacral disc angles in persons with and without defects in the pars interarticularis. AB - There remains a lack of definitive evidence regarding the etiology of pars defects, though evidence is mounting in favor of micro-trauma. Approximation of the articular facets, as occurs in subjects with increased sacral base angles, may result in greater stress to this area, leading to the development of pars defects. Alternatively, pars defects may facilitate approximation of the articular facets, resulting in a higher sacral base angle. The purpose of this study was to determine whether persons with spondylolysis have greater sacral base angles compared to persons without spondylolysis. The sacral base, sacrovertebral, and lumbosacral disc angles were measured on 30 subjects with radiographic evidence of spondylolysis at L5, and on 95 radiographically normal subjects. A 26% difference in the sacral base angle between spondylolytic and normal males was discovered. The results for females were inconclusive due to the sample size. Baseline data for the sacral base, sacrovertebral and lumbosacral disc angles were established for both normal and spondylolytic males and females. No relationship was found between spondylolysis and these two angles. PMID- 2273332 TI - A treatment for carpal tunnel syndrome: evaluation of objective and subjective measures. AB - This study was designed to assess the efficacy of a proposed new and unique program relative to treatment and troubleshooting for diagnostic causes of carpal tunnel syndrome (CTS). Objective measures of anthropometry, strength, range of motion, muscle activity, and task performance, together with subjective ratings of pain were observed in a group of individuals diagnosed with CTS. These measures were compared to a control population showing no symptoms of CTS prior to undergoing treatment and following completion of the treatment program. Results indicate that individuals with CTS had significantly lower values on some strength, range of motion, and slower task performance than did the control group. Ratings of pain and distress were also significantly higher than the controls, and in the literature the CTS group's values approached levels of chronic pain. Analysis of posttreatment cases revealed statistically significant improvements in several strength measures of up to 25% over pretreatment values. Significant improvement was also shown in several range of motion measures of up to 22%. Finally, a significant reduction of 15% in pain and distress ratings was demonstrated in the posttreatment cases. PMID- 2273331 TI - A retrospective consecutive case analysis of pretreatment and comparative static radiological parameters following chiropractic adjustments. AB - An investigation was undertaken to determine the effect of chiropractic adjustments on static radiological parameters. Standard plain film radiography was used. A retrospective consecutive case analysis approach was used for obtaining the data from the pretreatment and comparative posttreatment radiographs. Measurements for cervical lordosis, sacral base angle, lumbar lordosis, scapular angle, Cobb's angle and retrolisthesis of adjusted lumbar segments were determined by marking films in a blinded fashion. Intra- and interexaminer reliability for the measurement of cervical lordosis and retrolisthesis were determined to be excellent with a low standard error (Pearson's r range 0.89-0.97, p less than .001 for cervical lordosis and Pearson's r 0.74-0.90. p less than .001 for retrolisthesis). The data from pre- and comparative post-measurements of retrolisthesis showed a significant reduction of approximately 34%. No reduction was seen in a control group with retrolisthesis. No pre/post comparative changes were observed with cervical lordosis angle, sacral base angle, lumbar lordosis angle, scapular angle or Cobb's angle. PMID- 2273333 TI - Chiropractic education: a student survey. AB - This study surveyed 1296 chiropractic students, 724 (55.9%) of who were in their first term, and 569 (43.9%) who were beginning their second academic year (third term/fourth quarter). From the available students in 12 of the colleges participating in this study, 73.2% responded to the three-page questionnaire. Questions included the extent and specialization of previous education, population demographics, the application process, justification for separate health care professions, attitudes concerning the integration of chiropractic principles into the curriculum, the efficacy of chiropractic adjustments, and exposure to chiropractic prior to entering chiropractic college. Results showed that chiropractic students represent individuals from all walks of life, most of whom selected chiropractic as a first choice. They clearly distinguish between chiropractic physicians and medical doctors and are overwhelmingly convinced that the chiropractic adjustment is effective, especially if they had themselves received chiropractic care. Most entered chiropractic college with a nonchiropractic family background. PMID- 2273334 TI - Occipitalization of the atlas. AB - This paper discusses occipitalization of the atlas and its relationship to the chiropractic practitioner. Patients commonly consult a chiropractor with complaint of headache, suboccipital stiffness, restricted motion, dizziness and other symptoms related to the upper cervical region. Differential diagnosis of the exact etiological factor of these symptoms must be made via a thorough history, physical examination, and roentgenological examination. If occipitalization of the atlas is detected on the initial roentgenological examination, then follow-up magnetic resonance imaging, computerized tomography or linear tomographic studies may be warranted to rule out concomitant diverse osseous and/or neural anomalous conditions of the cervical spine which may easily mimic symptoms of disorders commonly treated by the chiropractic practitioner. The chiropractic practitioner must obtain appropriate roentgenological and other diagnostic imaging studies to ensure proper evaluation of the structural integrity of the cervical spine before appropriate treatment can be rendered. PMID- 2273335 TI - Effectiveness of chiropractic management for patellofemoral pain syndrome's symptomatic control phase: a single subject experiment. AB - Chiropractic management of patellofemoral pain syndrome has not been well documented. A time-series experimental design was employed to assess the effectiveness of chiropractic care during the symptomatic control phase in a patient with bilateral knee pain. Treatment consisted of long axis tibiofemoral adjustment, passive patellofemoral mobilization, and continuous ultrasound. Mediating variables, derived from physical examination findings, were subject to periodic randomized observation sampling by a second observer who was blinded to the first observer, but unblinded to the experimental phases. Strong interexaminer reliability (K = 0.78, p less than .005) was observed for patellar tracking jitter. Poor agreement (K = 0.31, NS) was observed for the patellar grinding test graded on an oridinal scale, but moderate interexaminer agreement (K = 0.52; p less than .01) was obtained with the test on a nominal scale. Clinical outcome measures of pain, patellar tracking, and patellar grinding tests were observed to visually covary throughout the experiment. A reliable 3-4 wk lag was observed between treatment phases and demonstrable changes in the patient's signs and symptoms. PMID- 2273337 TI - A review of the research papers published by the International College of Applied Kinesiology from 1981 to 1987. PMID- 2273336 TI - Interexaminer reliability of the innatometer. PMID- 2273338 TI - The chiropractic management and rehabilitation of cervical trauma. PMID- 2273339 TI - Brucellosis: a rare cause of the unstable spine. PMID- 2273340 TI - Commentary: the chiropractic paradigm. PMID- 2273341 TI - Occupational repetitive motion injury: clinical overview and chiropractic implication. PMID- 2273342 TI - Physician's Recognition Award recipients. PMID- 2273343 TI - Of joy and thankfulness. PMID- 2273344 TI - More non-MDs eligible for medical staffs. PMID- 2273345 TI - New "yardstick" needed to gauge hospital capacity utilization. PMID- 2273346 TI - Striking a balance. PMID- 2273347 TI - Quality predoctoral training in the ambulatory setting. PMID- 2273348 TI - Global health care: a look at the future. PMID- 2273350 TI - My ideals for the Medical Association of Georgia. PMID- 2273349 TI - Domestic violence: an analysis of battered women in Georgia. PMID- 2273351 TI - Georgia Supreme Court mandates disclosure of JCAHO accreditation reports. PMID- 2273352 TI - Asthma. PMID- 2273353 TI - Bias in case-control studies. A review. PMID- 2273354 TI - The ethics of resource allocation. Proceedings of a symposium held at the University of Manchester during the 33rd annual scientific meeting of the Society for Social Medicine, September 1989. PMID- 2273355 TI - Effects of ultrasound, shortwaves, and physical exertion on pregnancy outcome in physiotherapists. AB - STUDY OBJECTIVE: The aim of the study was to investigate whether occupational exposure among physiotherapists is associated with spontaneous abortion or congenital malformation in the offspring. DESIGN: The study was a retrospective nested case-control study, where the pregnancy outcome data were based on the medical registers. SETTING: All registered physiotherapists in Finland who had become pregnant during the study period were included in the study. SUBJECTS: Cases were defined as women who had been treated for spontaneous abortion during 1973-1983 or had delivered a malformed child during 1973-1982. One pregnancy per woman was randomly selected for the study. Three age matched (+/- 18 months) controls were selected for each abortion case and five for each malformation case. The final study population was 204 cases and 483 controls in the spontaneous abortion study, and 46 cases and 187 controls in the congenital malformation study. MEASUREMENTS AND MAIN RESULTS: Exposure information was collected by mailed questionnaires from 1329 women. The response rate was 92% in the spontaneous abortion study, and 89% in the congenital malformation study. Heavy lifting (including patient transfers) was associated significantly with spontaneous abortion. Exposure to ultrasound and shortwaves showed about threefold odds ratios for spontaneous abortions occurring after the 10th week of gestation but in analysis where potential confounding variables were controlled, neither reached statistical significance. Deep heat therapies together, and shortwaves alone, were associated significantly with congenital malformations, but the increase was found in the lower exposure category only. From the potential confounding variables, previous abortion (spontaneous or induced) was associated significantly with spontaneous abortion, and febrile disease in early pregnancy was associated with congenital malformation. CONCLUSION: Physical exertion during early pregnancy seems to be a risk factor for spontaneous abortion. The findings raise suspicion of the potential harmful effect of shortwaves and ultrasound on the pregnancy, but no firm conclusion can be drawn on the bases of these results alone. PMID- 2273356 TI - Use of questionnaires in a study of spontaneous abortion in a general population. AB - STUDY OBJECTIVE: The aim was to evaluate the appropriateness of postal questionnaires in studies of spontaneous abortion in a general population. DESIGN: Survey of spontaneous abortions by comparing diagnoses reported in questionnaires to information collected from hospital records and a discharge register. SETTING: The study took place in the general community. PARTICIPANTS: The study involved a random sample of 1400 women born between 1935 and 1960, living in two towns in the south west of Sweden. MEASUREMENTS AND MAIN RESULTS: 9% of spontaneous abortions among respondents were not reported in the questionnaire, and 31% were missing in the register; 80% of the spontaneous abortions reported in the questionnaire could be verified in hospital records, and a further 7% were mentioned in the records but not certified by a doctor; 97% of the diagnoses received by the women who had answered affirmatively to two complementary questions on spontaneous abortions could be found in the records. CONCLUSIONS: Postal questionnaires can be used in epidemiological studies of spontaneous abortions, among a general population as well as among occupational groups. PMID- 2273357 TI - Social determinants of nutrient intake in smokers and non-smokers during pregnancy. AB - STUDY OBJECTIVE: The aim was to investigate the effects of social factors (education, income, marital status, partners' employment status, housing tenure, social class), smoking, and maternal height on the dietary intake of pregnant women. DESIGN: The study was a prospective investigation on a two phase sample. SETTING: The study involved women attending the antenatal clinic at a district general hospital. PATIENTS: A group of pregnant Caucasian women, selected because they were heavy smokers (15+ cigarettes/day) (n = 94) and a randomly selected sample of never smokers (n = 112) were studied. MEASUREMENTS AND MAIN RESULTS: Data on social factors were collected by interviewer administered questionnaire. A 7 day weighed intake method was used to determine dietary intake at 28 weeks gestation. In univariate analyses, income, housing tenure and social class had significant effects on intakes of both macro- and micronutrients, and maternal education and smoking had significant effects on intakes of micronutrients. Using a stepwise multivariate analysis with income, smoking and maternal education, income was a significant factor in the intake of most nutrients but this effect disappeared when social class and housing tenure factors were entered into the model. Only social class and housing tenure had any significant effect on intakes of macronutrients--energy, protein and fat. Smoking and maternal education were the most important determinants of quality of diet (nutrient density); other factors had only negligible effects. Income was the only significant factor in alcohol intake. It is suggested that the effects of social class and income are overlapping. CONCLUSIONS: Smoking, being renters of accommodation, and being of minimum education and low social class are risk factors for poor dietary intake. It is recommended that such higher risk groups be specifically targeted for nutritional advice in pregnancy. PMID- 2273358 TI - Geographical variation in cancer patient survival in Finland: chance, confounding, or effect of treatment? AB - STUDY OBJECTIVE: The aim was to determine whether survival of cancer patients in Finland varies with their place of residence, and if so, what proportion of the variation might be due to health services rather than to confounding variables. DESIGN: Patients with breast and prostatic cancer diagnosed in Finland between 1970 and 1981 were classified by place of residence (from 21 hospital districts), and area specific 5 year relative survival rates were estimated. SETTING: This was a population based survey of the whole of Finland. PATIENTS: 16,754 cases of breast cancer and 9483 cases of prostatic cancer were identified. Of these, 0.5% of breast cancers and 4.1% of prostatic cancers were excluded because diagnosis was based only on necropsy findings or because the only information available was from the death certificate. MEASUREMENTS AND MAIN RESULTS: There was a large variation in rates, ranging from 59% to 76% for breast cancer, and from 30% to 65% for prostatic cancer. However, after accounting for age of patient and extent of disease, the standardised differences for prostatic cancer closely followed random distribution, indicating equal results of treatment in different areas. For breast cancer there was more variation than expected by chance and patients resident in any of the university central hospital districts with modern radiotherapy equipment survived better than other patients. CONCLUSIONS: There is little indication that large variations in crude mortality rates from these two cancers in different parts of Finland are due to inequalities of medical care, though a small effect on breast cancer survival which might be care related was shown. PMID- 2273359 TI - A cohort analysis of breast cancer, uterine corpus cancer, and childbearing pattern in Norwegian women. AB - STUDY OBJECTIVE: The aim was to study the influence of childbearing pattern on the incidence of breast cancer and uterine corpus cancer. DESIGN: This was an ecological study of birth cohorts of women. SETTING: The study was population based, involving the whole of Norway. PARTICIPANTS: The participants were Norwegian women born between 1890 and 1944. MEASUREMENTS AND MAIN RESULTS: Age specific fertility rates and age specific incidence rates for different birth cohorts were analysed by an age-cohort-period model where quantitative indices of the childbearing pattern substituted the cohort component. The 1890-94 birth cohort had the most favourable childbearing pattern with regard to the risk of breast cancer as well as uterine corpus cancer. The least favourable pattern was in the 1910-14 cohort for breast cancer and the 1940-44 cohort for uterine corpus cancer. In the analysis it is estimated that about 15% of the increase in incidence of breast cancer from 1955 to 1984 may be attributed to changes in the childbearing pattern of the cohorts under study. For cancer of the uterine corpus the corresponding fraction is about 27%. CONCLUSIONS: The study reveals that changes in childbearing pattern may explain a certain fraction of the observed increase in breast and uterine corpus cancer in Norway in the last 30 years, but the largest fraction must be accounted for by other factors. PMID- 2273360 TI - Colorectal cancer in the north and south of Ireland 1950-1984. AB - STUDY OBJECTIVE: Northern Ireland has the highest standardised mortality ratios for colon cancer in the United Kingdom and the Republic of Ireland has some of the highest mortality rates for cancer in the world. The aim of the study therefore was to investigate trends in colorectal cancer in the north and south of Ireland over the period 1950 to 1984. DESIGN: The study was a cohort analysis of deaths from colorectal cancer for ages 35-74 years by five year age groups, divided by sex. SETTING: This was a population study involving all cases reported to the Registrar General of Northern Ireland and the Eire Vital Statistics and Central Statistical Office during the study period. MEASUREMENTS AND MAIN RESULTS: As in mainland Britain, rectal cancer mortality declined in the north and the south during the study period, but the fall began sooner for males than females. Colon cancer mortality fell in the late 1950s but subsequently rose to its previous high levels. CONCLUSIONS: The observation that there were declines in mortality in the north and south of Ireland in the late 1950s does not support the hypothesis that altered diet due to war rationing in Great Britain and Northern Ireland underlay the fall in British colon cancer mortality after the war. The very high standardised mortality ratios for colon cancer in Northern Ireland highlight a continuing major public health problem in the region. PMID- 2273361 TI - Acute respiratory illness in Adelaide children: breast feeding modifies the effect of passive smoking. AB - STUDY OBJECTIVE: The aim was to investigate the relation between passive smoking and childhood acute respiratory illness. DESIGN: The study involved an initial postal survey on a random sample of children followed by a case-control study based on the survey. A respiratory illness score was calculated from maternal reports of episodes of illness in the previous 12 months. SETTING: The study was a population survey based on Adelaide metropolitan area in South Australia. PARTICIPANTS: The reference population (n = 13,996) was all live born children registered in South Australia in 1983 whose parents lived in Adelaide metropolitan area. Of these, 4985 families were contacted by post and from 2125 respondents, 1218 (58%) gave consent for home interview. "Cases" were children with respiratory illness scores in the top 20%, controlling for age and time of year (n = 258); "controls" were taken in the bottom 20% (n = 231). MEASUREMENTS AND MAIN RESULTS: Maternal smoking in the first year of life was associated with a doubling in relative odds of respiratory proneness in the child (odds ratio = 2.06, 95% CI 1.25-3.39) after adjustment for confounding by parental history of respiratory illness, other smokers in the home, use of group child care, parent's occupation, and levels of maternal stress and social support. There was no evidence that this association was attributable to differences in the way smoking and non-smoking parents perceived or managed childhood acute respiratory illness. Maternal smoking in the first year, without smoking in pregnancy, was also associated with increased risk of respiratory proneness (odds ratio 1.75, 95% CI 1.03-3.0), showing an effect of passive smoking independent of any in utero effect. There was a strong negative effect modification by breast feeding: relative odds of respiratory proneness with maternal smoking were seven times higher among children who were never breast fed than among those who were breast fed. CONCLUSIONS: The results suggest a relatively small but real effect of passive smoking on childhood acute respiratory illness. Effect modification by breast feeding may be due to a combination of behavioural and biological mechanisms. PMID- 2273362 TI - Regional variations in wheezing illness in British children: effect of migration during early childhood. AB - STUDY OBJECTIVE: The aim was to examine the regional distribution of wheezing illness among British children, and the age at which geographical differences may be determined. DESIGN: Cross sectional analyses and study of interregional migrants were used. SUBJECTS: The subjects were national cohorts of British children born in 1958 and 1970. MEASUREMENTS AND MAIN RESULTS: The regional distribution of wheezing illness showed significant heterogeneity at age 5 (1970 cohort) and 7 (1958 cohort). In both cohorts, children in Scotland had a low prevalence of wheeze, which could not be attributed to underreporting of mild cases. There was a less consistent tendency for high prevalence in Wales, and in the South Western and Midlands regions of England. In the 1958 cohort, the regional differentials diminished progressively with age and were negligible at age 23. There was a poor correlation between the regional distribution of childhood asthma and the common geographical pattern shown by eczema in infancy and hay fever at age 23. Analysis of interregional migrants suggested that the regional variation in each cohort at age 5-7 was primarily related to the region of current residence, and not to the region of birth. CONCLUSIONS: Genetic constitution, perinatal exposures, or early childhood experiences are unlikely to account for the regional variation in wheezing illness. Although local patterns of symptom reporting or disease labelling may be acquired by parents who move to a new region, environmental factors operating at a regional level probably determine the prevalence of asthma in primary school children. These influences do not appear to have long lasting effects upon the tendency to wheeze in adolescence and early adulthood. PMID- 2273363 TI - Pattern of childbearing and mortality in married women--a national prospective study from Norway. AB - STUDY OBJECTIVE: The aim of the study was to investigate the effect of different pattern of childbearing on total mortality. DESIGN: A cohort study with all currently married women aged 25 years or more at the Norwegian census in 1970 with follow up to the end of 1985. Information on childbearing was obtained by questionnaires collected by enumerators. Follow up on death was found by a linkage based on the unique Norwegian identification number, between census information and the death register in the Central Bureau of Statistics. SETTING: The study was a national population survey. PARTICIPANTS: A total of 822,593 women with 11.5 million years of follow up and 112,023 deaths. MAIN RESULTS: Nulliparous women had higher mortality than parous women in all age groups. Parity showed a weak association with increasing mortality among high parous women. Lowest mortality was found for parous women with 2-4 children and a late first and last birth, adjusted for socioeconomic group by level of women's education. CONCLUSION: The findings indicate that postponed childbearing may benefit the health of women. PMID- 2273364 TI - Incidence of fractures in a geographically defined population. AB - STUDY OBJECTIVE: The aim was to describe the population based age and sex specific incidence of fractures at different sites in a large English health district. DESIGN: Recording of fractures was accomplished by a specially constructed outpatient index and by record linkage to hospital inpatient information, for the three years surrounding the 1981 census. SETTING: The fracture index was held by the Department of Community Health in Leicester using data from the fracture clinic at the central large district general hospital, supplemented by hospital inpatient data from Trent Region and the two adjoining regions. PARTICIPANTS: The denominator population was the Leicestershire Health Authority resident population. In the three years, 12,711 fractures amongst males and 10,565 amongst females were recorded. MEASUREMENTS AND MAIN RESULTS: The overall estimated annual incidence of fractures was 100 per 10,000 population for males and 81 per 10,000 population for females. Below the age of 55 years all fractures showed a higher incidence amongst males but amongst the over 55s, there was a consistent fall in the male:female incidence ratio with some sites showing a striking female preponderance. The results also show an apparent age specific temporal increase in incidence at certain fracture sites compared with earlier British data, but fracture incidence figures still suggest lower rates in this country than in North America and some Scandinavian countries. CONCLUSIONS: These findings provide population based incidence data on a major public health problem and are consistent with the major determinants of osteoporosis and increase in falls in postmenopausal women. The temporal and geographical variation in fracture incidence remain to be explained. PMID- 2273365 TI - Willingness to accept risk in the treatment of rheumatic disease. AB - STUDY OBJECTIVE: The aim was to assess patients willingness to accept mortal risk in the drug treatment of chronic rheumatic disease. DESIGN: A non-random sample of consecutive patients were interviewed with a standardised survey instrument. SETTING: The study took place in the Royal National Hospital for Rheumatic Diseases, Bath, UK. PATIENTS: 100 consecutive in- and out-patients aged 65 or less were interviewed, 50 with rheumatoid arthritis and 50 with ankylosing spondylitis. Mean age was 48 years with mean disease duration of 14 years. The rheumatoid arthritis group was mainly female (84%), v 26% in the ankylosing spondylitis group. MEASUREMENTS AND MAIN RESULTS: Risk preferences were elicited using the method of standard gamble in the context of a hypothetical new drug. Patients indicated the maximum percentage probability of mortality they regarded as acceptable to achieve four different levels of benefit: total cure (20.7%), relief of pain (16.9%), relief of stiffness (13.1%), return to normal functioning (14.5%). Rheumatoid arthritis patients displayed a higher (p less than 0.05) willingness to accept risk than ankylosing spondylitis patients for all gambles except relief of stiffness. Analysis of variance indicated that willingness to accept risk decreases with the duration of disease and increases with reductions in self assessed health status. CONCLUSIONS: Evaluative methods such as standard gamble can elicit useful risk-benefit preference data from patients to assist those who manage clinical risks. PMID- 2273366 TI - Probability and peer review. PMID- 2273367 TI - The right to die. Are living wills adequate? PMID- 2273368 TI - "The big change in medicine". PMID- 2273369 TI - National Practitioner Data Bank. PMID- 2273370 TI - The power nap. PMID- 2273371 TI - Medicine and Spanish control. Historical issue. PMID- 2273372 TI - Military medicine in Florida. The first 200 years. PMID- 2273373 TI - Medicine in Florida during the second Spanish period. 1783-1821. PMID- 2273374 TI - European medicine in America before Florida's discovery. The fleet physician. PMID- 2273375 TI - Hospital military. Perspectives on history and survival. Second Spanish period to the present. PMID- 2273377 TI - Medi-Car. PMID- 2273376 TI - The Julia Street building and public health. PMID- 2273378 TI - Medical history of Florida. PMID- 2273379 TI - Cytokines. From the laboratory to the clinic. PMID- 2273380 TI - Mutational analysis of plum pox potyvirus polyprotein processing by the NIa protease in Escherichia coli. AB - A binary Escherichia coli expression system has been used to study the pathway for proteolytic processing of the plum pox potyvirus (PPV) polyprotein. Trans cleavage at the carboxyl end of the cylindrical inclusion protein occurred, although with lower efficiency than that at the large nuclear inclusion protein capsid protein junction. No trans cleavage at the carboxyl end of the small nuclear inclusion protein (NIa) was detected. The proteolytic activities at different cleavage sites of several deletion and point mutations of NIa protein have been analysed. The large delta SX deletion and two different point mutations at His 239 abolished proteolytic activity at all sites. The effect of other mutations, particularly a Glu substitution for Asp 274, depended on the particular cleavage site analysed. The results obtained with the PPV NIa protein mutants were similar to those reported for comparable mutations in the tobacco etch virus 49K protease, despite differences in the sequences recognized for processing. No evident competitive inhibition of the proteolytic activity of PPV NIa protease by the presence of an excess of the different protease mutants could be demonstrated. PMID- 2273381 TI - Nucleotide sequence of barley yellow mosaic virus RNA 1: a close evolutionary relationship with potyviruses. AB - The complete nucleotide sequence of barley yellow mosaic virus (BaYMV) RNA 1 was obtained by analysis of overlapping cDNA clones and by direct RNA sequencing. The sequence is 7632 nucleotides in length, excluding a 3' poly(A) tail. The first AUG codon at nucleotide 172 appeared to be the initiator for a single long open reading frame encoding a protein of 2410 amino acids with an Mr of 270,755. Amino acid sequence comparisons revealed that the BaYMV 270K protein contains three regions upstream of the C-terminal capsid protein which share significant homologies with the cytoplasmic inclusion and two nuclear inclusion proteins of potyviruses thus indicating their similarities in genetic organization. However, the apparent low levels of homology in the corresponding proteins of BaYMV and potyviruses are in contrast with the high conservation among potyviruses. Moreover, our data indicate that BaYMV RNA 1 has no counterpart to the two cistrons located in the 5'-terminal region of the potyvirus genome. Although the data suggest a close evolutionary relationship between BaYMV and potyviruses, the striking differences set BaYMV apart from potyviruses. PMID- 2273383 TI - Serological differentiation of 20 isolates of tomato spotted wilt virus. AB - Twenty tomato spotted wilt virus (TSWV) isolates were serologically compared in ELISA employing five different procedures using a rabbit polyclonal antiserum against nucleocapsid proteins (NuAbR) and mouse monoclonal antibodies (MAbs), two directed to nucleocapsid proteins (N1 and N2) and four directed to glycoproteins G1 to G4. All the antisera were raised against TSWV-CNPH1. The 20 isolates were differentiated into two distinct serogroups. Serogroup I consisting of 16 isolates strongly reacted with NuAbR. The other four isolates were poorly recognized by NuAbR and were placed in another serogroup, designated II. The panel of MAbs differentiated the TSWV isolates into three serotypes. The 16 isolates forming serogroup I reacted strongly with the MAbs generated and were identified as serotype I isolates. The four isolates which made up serogroup II were split into serotypes II and III. The serotype II isolates did not respond or responded poorly with MAbs N1, N2 and G3. The two other isolates placed in serotype III were recognized by N1 but not by N2 and G3. Two isolates became defective after several mechanical passages and failed to respond or responded very poorly with MAbs directed to glycoproteins. Our results show that ELISA employing polyclonal and monoclonal antisera is a useful tool to differentiate TSWV isolates and to detect defective forms. The results also strongly suggest that TSWV nucleocapsid proteins are less conserved than the glycoproteins. PMID- 2273382 TI - Nucleotide sequences of coat protein genes for three isolates of barley yellow dwarf virus and their relationships to other luteovirus coat protein sequences. AB - Barley yellow dwarf virus (BYDV) can be separated into two groups based on, among other criteria, serological relationships that are presumably governed by the viral capsid structure. Nucleotide sequences for the coding regions of coat proteins of approximately 22 K were identified for the MAV-PS1, P-PAV (group 1) and NY-RPV (group 2) isolates of BYDV. The MAV-PS1 and P-PAV coat protein sequences shared 71% deduced amino acid similarity whereas that of the NY-RPV isolate shared no more than 51% similarity with either the MAV-PS1 or the P-PAV sequence. Other comparisons showed that these and other BYDV coat protein sequences examined to date share a high degree of identity with those identified from other luteoviruses. Among luteovirus coat protein sequences in general, several highly conserved domains were identified whereas other domains differentiate MAV-PS1 and PAV isolates from NY-RPV and other luteoviruses. Sequence similarities and differences among BYDV coat proteins (approx. 22K) are consistent with the serological relationships exhibited by these viruses. Amino acid sequence comparisons between BYDV isolates that share common aphid vectors indicate that it is unlikely that these coat proteins are involved in aphid specificity. PMID- 2273384 TI - Complementarity between the 5'- and 3'-terminal sequences of rice stripe virus RNAs. AB - The 5' and 3' termini of four ssRNA species of rice stripe virus (RSV) isolate T were sequenced. The 3' termini of the three smallest ssRNAs, i.e. RNAs 2, 3 and 4, had the sequence 5' GACUUUGUGU 3'; that of ssRNA 1 had the sequence 5' GACUAUGUGU 3'. The 5'-terminal sequences of all four ssRNAs were 5' ACACAAAGUCC 3'. The 5'- and 3'-terminal sequences of about 20 bases of each ssRNA were almost complementary to each other. It is possible that RSV RNAs form panhandle structures characteristic of the RNA of negative-strand viruses. PMID- 2273385 TI - Characterization of the infection cycle of the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus in Lymantria dispar cells. AB - To characterize the infection cycle of the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus in Lymantria dispar cells, the time course of DNA synthesis and polyhedron production, and the onset and rate of budded virus production were investigated at three different m.o.i. (5, 10 and 100). In addition, the time course of expression of three proteins (gp64, p39 and polyhedrin) representative of three temporal classes of baculovirus genes was also analysed using Western blot analysis. DNA synthesis began at 12 to 18 h post infection (p.i.). The rate of budded virus (BV) production reached maximal levels at 24 to 36 h p.i. and continued at high levels indicating that BV production was not turned off late in infection. Polyhedra were first observed at 48 h p.i. The m.o.i. appeared to influence the magnitude but not timing of early events in the viral infection cycle (gp64 expression and DNA synthesis) and also influenced the initial levels of BV production and the percentage of cells containing occlusion bodies. The m.o.i. had little influence on the final rates of BV production and the time of detection of p39 and polyhedrin on Western blots. PMID- 2273386 TI - Localization of adenovirus-encoded DNA replication proteins in the nucleus by immunogold electron microscopy. AB - The distribution of three adenovirus-encoded DNA replication proteins in the nucleus of human 293 cells was studied by immunogold electron microscopy. The infected nuclei contained four morphologically distinct inclusions. They were highly electron-dense granules (type I), compact fibrogranular masses of medium electron density (type II), filamentous masses of low electron density (type III) and large polygonal crystals (type IV). In immunogold labelling studies, antibodies to the adenovirus single-stranded DNA-binding protein (DBP) and antibodies to single-stranded DNA showed extensive binding to the type III inclusions. The antibodies to the adenovirus DNA polymerase (AdPol) and terminal protein (TP) predominantly labelled type II inclusions. Double immunogold labelling studies detected low levels of AdPol and TP in type III inclusions and DBP in type II inclusions. The selective distribution of DNA replication proteins suggests that the type II and III inclusions represent two functionally different entities that may be involved in two different aspects of adenovirus DNA replication, i.e. chain initiation and elongation. PMID- 2273387 TI - Characterization of antibody and cytotoxic T lymphocyte responses to human influenza virus H3 haemagglutinin expressed from the haemagglutinin locus of vaccinia virus. AB - Antibody and cytotoxic T lymphocyte (CTL) responses to the haemagglutinin (HA) of human H3N2 influenza virus were analysed, using recombinant vaccinia viruses containing the influenza HA gene inserted into the HA gene locus of vaccinia virus. The recombinant vaccinia viruses elicited a high haemagglutination inhibiting (HI) antibody response to the homologous influenza virus in mice. In addition, HI antibody generated by the recombinant vaccinia virus reacted with antigenic variants of human H3N2 influenza virus in a manner similar to that elicited by the HA vaccine. Mice with a high response to influenza virus HA vaccine were highly responsive to the HA expressed from the recombinant vaccinia virus, as measured by HI antibody production. The immunogenicity of the influenza virus HA expressed by the recombinant seems to be attributable to the intrinsic immunogenicity of the HA molecule. The recombinants primed mice for an influenza virus H3-specific CTL response and primed CTLs recognized the target cells in a subtype-specific manner. The results indicate that a recombinant vaccinia virus derived by the insertion of a foreign gene into its HA gene locus is a potent live vaccine not only for eliciting a high antibody response but also for priming a specific CTL response. PMID- 2273388 TI - Theiler's murine encephalomyelitis virus-binding activity on neural and non neural cell lines and tissues. AB - Three categories of cell lines are described with respect to their activity in binding Theiler's murine encephalomyelitis virus (TMEV). High, medium and low densities of viral receptors can be detected on cell lines from different species and origins by using an immunological binding assay. Nevertheless, TMEV acts as a fastidious virus that only infects a few cell types productively. No correlation between virion binding and degree of permissiveness to infection could be detected. The presence of viral receptors in both susceptible and resistant strains of mice seemed to have a widespread tissue distribution, the thymus being an exception. When primary cerebral cultures, enriched in neurons, astrocytes or oligodendrocytes, were checked in the immunological assay, a higher density of viral receptors was detected in the neuronal population. The number of virus binding sites in the BHK-21 cell line is reported here to be 5 x 10(3) per cell; approximately 15 x 10(3) and 2.5 x 10(3) are the estimates of binding sites per cultured neuron and macroglial cell, respectively. PMID- 2273389 TI - Liposomes modulate human immunodeficiency virus infectivity. AB - We have investigated the effects of the fusion of liposomes with human immunodeficiency virus type 1 (HIV-1LVA) on the ability of the virus to infect CD4+ and CD4- cells. Fluorescence dequenching measurements indicated that HIV-1 fuses with liposomes composed of either cardiolipin (CL) or N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethyl ammonium chloride (DOTMA) but not appreciably with dioleoylphosphatidylcholine (DOPC) liposomes. Pre-incubation of HIV-1 with DOTMA liposomes enhanced virus production (measured by p24 gag antigen production in the culture medium and in situ) in CD4+ A3.01 and H9 cells in a concentration dependent manner, but did not mediate the infection of the CD4- cell line, K562. Preincubation of HIV-1 with between 10 and 30 microM-DOTMA liposomes, and subsequent incubation with A3.01 cells, resulted in the production of about 30 fold greater levels of virus than controls. The presence of DOTMA liposomes during the incubation of A3.01 cells with HIV-1 enhanced the infectivity of the virus up to 90-fold compared to controls. Conversely, preincubation of HIV-1 with CL liposomes inhibited infection of A3.01 cells, dependent on the concentration of liposomes; DOPC liposomes did not alter the infectivity of the virus under any of the incubation conditions. Our results thus indicate that fusion of HIV-1 with liposomes alters the ability of the virus to infect its target cells. PMID- 2273390 TI - Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. AB - Although its underlying mechanisms are poorly understood, data comparing each of the four dengue virus serotypes suggest that in vitro antibody-dependent infection enhancement is a reproducible and measurable phenomenon related to other serological measures of antibody-virus binding. Information characterizing infection enhancement may provide clues to disease pathogenesis for dengue and other viruses that exhibit antibody-enhanced infection. We propose criteria for the detection and quantification of in vitro antibody-dependent enhancement of flavivirus infection based on observations using all four dengue virus serotypes, macrophage-like cell lines and human peripheral blood monocytes, and various immune sera and monoclonal antibodies. It is proposed that antibody-dependent infection enhancement is defined by the following findings: (i) significantly increased virus production is measured in quantitative assays at different points on the growth curve; (ii) assays of the virus output of cells infected with mixtures of constant amounts of virus and serial dilutions of the pre-existing antibody source produce characteristic 'enhancement profiles' of rising and falling virus output over at least a 10(-3)-fold dilution range; (iii) for each enhancing antibody source the dilution producing maximal infection enhancement is related to other serological measures of binding to the envelope, or another virus component; (iv) infection enhancement is detected with different antibody sources and virus strains (when available) tested over a range of m.o.i.; (v) other causes of enhanced virus production are ruled out. PMID- 2273391 TI - Genetic variation of Japanese encephalitis virus in nature. AB - Forty-six strains of Japanese encephalitis (JE) virus from a variety of geographic areas in Asia were examined by primer-extension sequencing of the RNA template. A 240 nucleotide sequence from the pre-M gene region was selected for study because it provided sufficient information for determining genetic relationships among the virus isolates. Using 12% divergence as a cutoff point for virus relationships, the 46 isolates fell into three distinct genotypic groups. One genotypic group consisted of JE virus isolates from northern Thailand and Cambodia. A second group was composed of isolates from southern Thailand, Malaysia, Sarawak and Indonesia. The remainder of the isolates, from Japan, China, Taiwan, the Philippines, Sri Lanka, India and Nepal, made up a third group. The implications of these findings in relation to the epidemiology of JE are discussed. Results of this study demonstrate that the comparison of short nucleotide sequences can provide insight into JE virus evolution, transmission and, possibly, pathogenesis. PMID- 2273392 TI - Herpesviral deoxythymidine kinases contain a site analogous to the phosphoryl binding arginine-rich region of porcine adenylate kinase; comparison of secondary structure predictions and conservation. AB - Twelve herpesviral deoxythymidine kinases were examined for regions of sequence similarity by multiple alignment. Six highly conserved sites were observed. Site 1 corresponded to a glycine-rich loop that forms part of the ATP-binding pocket in porcine adenylate kinase (PAK), and site 5 corresponded to a region in PAK, located on one lobe of the cleft, that contains arginine residues that bind substrate phosphoryl groups. Site 3, consisting of the motif -DRH-, is thought to be involved in thymine/deoxythymidine recognition; site 4, which is nearby, probably participates in this function as well. The functions of sites 2 and 6 have not been identified. Secondary structure predictions were made by the Garnier method and averaged for each position in the multiple alignment. The structure predicted for all six sites was typically a short flexible region (turn or coil) at or adjacent to the site, flanked by rigid structures (helix or sheet) on either side. PMID- 2273394 TI - Nucleotide sequence and transcriptional analysis of the HindIII P region of a temperature-sensitive mutant of Autographa californica nuclear polyhedrosis virus. AB - DNA sequence analysis of the HindIII P region of a temperature-sensitive mutant of Autographa californica nuclear polyhedrosis virus confirmed the specific amplification of 1.4 kb of viral DNA from this region of the genome. The sequenced region included an open reading frame, translated in a counterclockwise direction, which would potentially encode a 74K protein. The amplified DNA was contained within this open reading frame, resulting in in-frame amplifications of a domain within the protein. Transcription studies revealed the presence of a ladder of viral RNA species corresponding to a 2.5 kb transcript carrying tandem repeats of about 1.4 kb. This indicated that the duplicated DNA was transcribed in the same orientation as the p10 gene. We predict that transcripts synthesized from the opposite DNA strand also consist of a ladder of related mRNAs which would be translated to produce a family of p74 proteins with multiple internal domains. PMID- 2273393 TI - The two open reading frames of the 22K mRNA of human respiratory syncytial virus: sequence comparison of antigenic subgroups A and B and expression in vitro. AB - The sequence of the 22K mRNA of strain 18537 of antigenic subgroup B of human respiratory syncytial virus (RSV) was determined by sequencing cloned cDNAs of intracellular mRNA. Comparison with the corresponding sequence of the A2 strain of subgroup A showed that there is 78% nucleotide sequence identity overall, that the amino acid sequence of the 22K protein is 92% identical between subgroups and that the 22K mRNA of both subgroups contains a second, internal, overlapping open reading frame (ORF) whose length, nucleotide sequence and potential translational start and stop sites were highly conserved and whose predicted product has 62% amino acid identity between subgroups. Sequence analysis of 36 cDNAs of intracellular 22K mRNA of strain A2 did not detect nucleotide insertions or deletions in the region of overlap between the two ORFs, indicating that the majority of intracellular 22K mRNA is a faithful copy containing the two distinct ORFs. Translation in vitro of mRNAs transcribed from engineered cDNAs showed that an mRNA which contained only the second, internal ORF directed the synthesis of a previously unidentified polypeptide of the predicted size, whereas mRNA representing the complete gene directed the synthesis of both the 22K protein and the product of the internal ORF. This latter species was synthesized in vitro as a discrete, separate protein rather than as a fusion protein. It is not yet known whether this protein is synthesized in RSV-infected cells. PMID- 2273395 TI - Translocation and cleavage of rubella virus envelope glycoproteins: identification and role of the E2 signal sequence. AB - The structural proteins of rubella virus (RV) are translated as a large polyprotein precursor, p110, which is processed to produce the mature virion components, the 33K capsid protein (C) and the two envelope glycoproteins, E1 (58K) and E2 (42K to 47K). The precise processing mechanism has not been elucidated; however it must include at least two proteolytic cleavages to release the individual virion components from the polyprotein, and it must provide for their dichotomous intracellular distribution. The C protein remains in the cytoplasm where it participates in the formation of nucleocapsids, while the envelope glycoproteins enter the cellular secretory pathway and are N glycosylated and cleaved. Sequence analysis of the 24S mRNA encoding the polyprotein precursor suggests that both E1 and E2 are preceded by signal peptides for translocation across the membrane of the rough endoplasmic reticulum. A recent study has provided direct evidence that the putative signal peptide preceding E1 can in fact mediate translocation of E1. In this study, we have used in vitro translation-translocation assays to examine further the processing of RV glycoproteins. We have shown that the putative signal sequence preceding E2 can mediate translocation of the E2 protein in the absence of an intact E1 signal peptide. The experiments also revealed that cleavage of the E2 E1 polyprotein requires (i) the E2 signal peptide, (ii) microsomal membranes and (iii) sequences beyond the proximal half of the E1 signal peptide. Together these results suggest that separation of the E2 signal sequence as well as the proteolytic cleavage of E1 from E2 is performed by the cellular enzyme, signal peptidase. PMID- 2273396 TI - Segment 5 of the rice dwarf virus genome encodes a protein highly conserved within the phytoreoviruses. AB - The complete nucleotide sequence of segment 5 (S5) of the rice dwarf virus (RDV) genome was determined. RDV S5 is 2571 bp in length and has a single long open reading frame which encodes a polypeptide of 801 amino acids (Mr 90495). When compared to the wound tumor virus genome S5, there was 56.9% and 52.8% similarity in the nucleotide and amino acid sequences, respectively. This high similarity suggests that the S5 proteins of these viruses are functionally similar. PMID- 2273397 TI - The primary structure of the virion protein gene and encoded protein of erysimum latent tymovirus. AB - The nucleotide sequence of the virion protein (VP) gene of erysimum latent tymovirus (ELV) has been determined and the amino acid sequence of the VP deduced and confirmed by peptide analysis. The ELV VP is larger than the VPs of other tymoviruses because it has, unexpectedly, 11 more amino acid residues at its N terminus. The amino acid sequences of the VPs of ELV and four other tymoviruses align unequivocally and their relationships, as assessed from the percentage of identical residues, correlate well with previously reported serological tests which have shown ELV to be distant from other tymoviruses. PMID- 2273398 TI - Sexual dimorphisms in the vocal control system of a teleost fish: morphology of physiologically identified neurons. AB - In one species of vocalizing (sonic) fish, the midshipman (Porichthys notatus), there are two classes of sexually mature males--Types I and II--distinguished by a number of traits including body size, gonad size, and reproductive tactic. The larger Type-I males (unlike Type-II males and females) build nests, guard eggs, and generate several types of vocalizations. Sound production by Type-I males is paralleled by a proportionate increase of 600% in their sonic muscle mass. The motor volley from ventral occipital roots innervating the sonic muscles establishes their contraction rate and, in turn, the fundamental frequency of emitted sounds. Electrical stimulation of the midbrain in every male and female elicited a rhythmic sonic discharge as recorded in the occipital roots; however, the fundamental frequency was slightly, but significantly, higher (20%) in Type-I males. Intracellular recording from identified motoneurons and presumed presynaptic "pacemaker" neurons showed their synaptic and action potentials had the same frequency as that of the nerve volley in every male and female. Reconstructions of physiologically identified motoneurons and pacemaker neurons following intracellular horseradish-peroxidase (HRP) filling showed their somata and dendrites to be 100-300% larger in Type-I males. These data unambiguously show that the size of a target muscle is correlated with the size of both the respective motoneurons and their presynaptic afferent neurons. As discussed, this implies that the dramatic increase in neuron size in the sonic motor system of Type-I males is causally dependent upon expansion of the sonic muscle. It is further likely that the more modest sex difference in the rhythmic central discharge is established by the intrinsic membrane properties of sonic neurons. These results also corroborate, at a number of behavioral, morphological, and neurophysiological levels, that the sonic motor system of "sneak spawning" Type II males is similar to that of females. Thus, unlike the vocalizing Type-I males, sexual differentiation of the reproductive system in Type-II males is not linked to concomitant changes in the neurophysiological and morphological features of the sonic motor circuit. PMID- 2273399 TI - Social control of neuronal soma size. AB - Factors responsible for sexual maturation differ significantly among vertebrate species. In many, age is most important, whereas in others seasonal or social cues play a central role. Here we report that maturation in the African cichlid fish Haplochromis burtoni is socially controlled, and that this control includes regulation of soma growth in a population of preoptic neurons immunoreactive to gonadotropin-releasing hormone (irGnRH). Males reared in aquaria among fish of the same age mature sexually in about 3 months, whereas males reared in the presence of older, more aggressive conspecifics remain immature even at 5 months of age. Immature males display hypogonadism and have conspicuously undersized preoptic irGnRH neurons in comparison to those of mature siblings of the same age. This variable maturation rate increases the likelihood that individual males will survive to an age when they can successfully reproduce. PMID- 2273400 TI - Topographical features of the substratum for growth of pioneering neurons in the Manduca wing disc. AB - The sensory neurons of the Manduca wing form a planar network nestled between the wing's upper and lower monolayers. The pioneering axons of this network grow in a distal-to-proximal direction over the basal surface of the upper epithelial monolayer. The basal surface of this monolayer has been examined ultrastructurally during the period of axonal outgrowth. The cellular terrain traversed by axons shows a graded distribution of epithelial processes, with the number of processes increasing in a proximal direction. Growth cones of axons, therefore, encounter increasing surface areas for contact with their substratum as they move toward the base of the wing. Because a basal lamina is laid down over these epithelial processes after axons have pioneered the neural pathways of the wing, axonal guidance cues apparently lie on surfaces of these basal processes. At branch points of the neural pathway examined in this study, axons avoid pathways in which the basal surfaces of cells in the upper wing monolayer interdigitate with basal surfaces of underlying tracheal cells. This interaction between wing epithelial cells and tracheal epithelial cells could act as a physical barrier to axonal outgrowth. PMID- 2273401 TI - Parallel motor pathways from thoracic interneurons of the ventral giant interneuron system of the cockroach, Periplaneta americana. AB - The data described here complete the principal components of the cockroach wind mediated escape circuit from cercal afferents to leg motor neurons. It was previously known that the cercal afferents excite ventral giant interneurons which then conduct information on wind stimuli to thoracic ganglia. The ventral giant interneurons connect to a large population of interneurons in the thoracic ganglia which, in turn, are capable of exciting motor neurons that control leg movements. Thoracic interneurons that receive constant short latency inputs from ventral giant interneurons have been referred to as type A thoracic interneurons (TIAs). In this paper, we demonstrate that the motor response of TIAs occurs in adjacent ganglia as well as in the ganglion of origin for the TIA. We then describe the pathway from TIAs to motor neurons in both ganglia. Our observations reveal complex interactions between thoracic interneurons and leg motor neurons. Two parallel pathways exist. TIAs excite leg motor neurons directly and via local interneurons. Latency and amplitude of post-synaptic potentials (PSPs) in motor neurons and local interneurons either in the ganglion of origin or in adjacent ganglia are all similar. However, the sign of the responses recorded in local interneurons (LI) and motor neurons varies according to the TIA subpopulation based on the location of their cell bodies. One group, the dorsal posterior group, (DPGs) has dorsal cell bodies, whereas the other group, the ventral median cells, (VMC) has ventral cell bodies. All DPG interneurons either excited postsynaptic cells or failed to show any connection at all. In contrast, all VMC interneurons either inhibited postsynaptic cells or failed to show any connection. It appears that the TIAs utilize directional wind information from the ventral giant interneurons to make a decision on the optimal direction of escape. The output connections, which project not only to cells within the ganglion of origin but also to adjacent ganglia and perhaps beyond, could allow this decision to be made throughout the thoracic ganglia as a single unit. However, nothing in these connections indicates a mechanism for making appropriate coordinated leg movements. Because each pair of legs plays a unique role in the turn, this coordination should be controlled by circuits dedicated to each leg. We suggest that this is accomplished by local interneurons between TIAs and leg motor neurons. PMID- 2273402 TI - Lateralization of syringeal function during song production in the canary. AB - The canary (Serinus canaria) vocal organ, the syrinx, has two separate sound sources, one in the cranial end of each bronchus. Previous investigations of whether song syllables are produced unilaterally or bilaterally have provided two contradictory results, as one researcher suggested that almost all syllables are produced by the left side of the syrinx alone, whereas another researcher suggested that both sides contribute similarly to all syllables. Our experiments, which involved unilateral bronchus plugging followed later by denervation of the ipsilateral syringeal muscles, attempted to resolve this disagreement. The males with right bronchus plugs, singing on the left side of the syrinx alone, produced nearly normal songs, whereas the birds with left bronchus plugs, singing on the right side, sang quite poorly. Interpretation of these data is difficult because it is not clear how syringeal function would be affected if the airflow rate through the intact side is increased above normal, nor is it known if the bird can compensate for bronchus occlusion. Nonetheless, we suggest that in male canaries most syllables are normally sung by the left side alone, with some syllables being produced by the right side alone and some being sung by both sides together. Right nerve section had little effect on the right-bronchus plugged males' ability to sing, but the repertoires of the left-plugged males were altered after left nerve section, indicating the possibility that signals carried by the left nerve exert an influence on the contralateral side. PMID- 2273403 TI - Neuromuscular development following tetrodotoxin-induced inactivity in mouse embryos. AB - Developmental aspects of the neuromuscular system in mouse embryos chronically paralyzed in utero with tetrodotoxin (TTX) between embryonic days 14 and 18 were studied using biochemical and histological methods. The number of lumbar spinal motoneurons (MNs) was higher in inactive embryos than in controls suggesting a decreased motoneuron cell death. In association with the increase in MN number, choline acetyltransferase activity was significantly increased in both spinal cord and peripheral synaptic sites. Paralyzed muscles exhibited a decreased number of mature myofibers and the nuclei were centrally located. Creatine kinase activity was greatly decreased and total acetylcholine receptor and receptor cluster numbers per myofiber were significantly increased in paralyzed muscles. A similar pattern of changes occurs in the neuromuscular system of the mutant mouse muscular dysgenesis (mdg). However, in contrast to the mdg mutant, tetrodotoxin treated muscles were similar to controls in their innervation pattern, in the ultrastructural aspects of the excitation-contraction coupling system (i.e., dyads and triads) and in the extent of dihydropyridine binding. Thus, neuromuscular inactivity is not sufficient to impair the pattern of muscle innervation or the appearance of either the triadic junctions or dihydropyridine receptors. These results indicate that alterations of dihydropyridine binding sites and triads in muscular dysgenesis cannot be accounted for by inactivity but rather must reflect a more primary defect involving the structural gene(s) regulating the development of one or more aspects of muscle differentiation. PMID- 2273404 TI - Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein. AB - Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS. PMID- 2273405 TI - The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia. AB - We studied whether small variations in intraischemic brain temperature influence the response of the blood-brain barrier (BBB) to transient forebrain global ischemia. Six animal subgroups included rats whose brain temperature was maintained at 30, 33, 36 or 39 degrees C during 20 minutes (min) of 4-vessel occlusion. Control rats without ischemia had brain temperature maintained between 30 and 39 degrees C for a 20 min period. After a 45 min postischemic recirculation period, rats were injected with the protein tracer, horseradish peroxidase (HRP), and perfusion fixed 5 or 15 min later. Control rats showed no leakage of the tracer protein. Postischemic rats in which brain temperature was controlled at either 30 or 33 degrees C failed to demonstrate consistent BBB alterations. In contrast, foci of cortical HRP extravasation were consistently documented in rats whose intraischemic brain temperature was 36 degrees C. Permeability alterations were more widespread in the 39 degrees C ischemic group and occurred in cortical, thalamic, hippocampal and striatal regions. The HRP extravasation frequently involved arterioles surrounded by perivascular spaces. Routes of increased permeability to HRP included endothelial pinocytosis, opening of the interendothelial tight junctions and diffuse leakage through damaged endothelial cells. These results demonstrate that brain temperature is a critical factor in determining whether BBB dysfunction is an acute consequence of a transient cerebral ischemic insult. PMID- 2273406 TI - Neuropathological diagnosis of Alzheimer disease. PMID- 2273407 TI - Characteristics of oculomotor disorders of a family with Joseph's disease. AB - The oculomotor abnormalities of 12 patients of a large Japanese family with Joseph's disease were investigated and compared with those of 27 patients with olivopontocerebellar atrophy (OPCA). All 12 patients had limitation of upward gaze, impairment of convergence and horizontal gaze nystagmus. However, none had abnormalities of pupillary shape or light reflexes. Impairments of saccadic and pursuit eye movements were frequently present. Further, difficulty of eyelid opening, bulging eyes, impairment of optokinetic and caloric responses and square wave jerks were seen in some of the patients. The autopsy examination of 1 patient revealed marked neuronal loss in the oculomotor nucleus with preservation of the Edinger-Westphal nucleus and neuronal decrease, myelin loss and gliosis of the dorsal midbrain including superior colliculus, pretectum and posterior commissures. Disturbance of upward gaze, sparing of pupillary light reflexes and horizontal gaze nystagmus were frequent and early symptoms. The pattern of oculomotor disturbances is different from that of OPCA and evaluation of the oculomotor system is useful for clinical diagnosis of the disease. PMID- 2273408 TI - Ataxia in myxoedema: a neurophysiological reassessment. AB - In a long-standing case of myxoedema with ataxia and dysarthria, neurophysiological investigations were carried out to assess how much of the ataxic dysbasic syndrome depended on the slowness of mechanical contraction and how much resulted from primary cerebellar involvement. It was observed that the Achilles reflexogram showed a marked prolongation of contraction and relaxation time and that in both quadriceps and triceps surae mechanical percussion induced a marked myxoedema and prolonged relaxation time. The EMG of these muscles during voluntary contraction and stopping reaction detected an excessive recruitment of the antagonistic muscles, starting without any abnormal delay, a finding at variance with a typical cerebellar pattern. Post-urographic analysis gave a pattern of oscillations still within the normal range. These findings suggest that the gait alterations of our patient depended on the increase in muscle contraction time and the consequent excessive recruitment of the antagonists. PMID- 2273410 TI - Transcranial magnetic stimulation: specific and non-specific facilitation of magnetic motor evoked potentials. AB - Different physiological mechanisms of facilitation of latencies and amplitudes of magnetic motor evoked potentials (MEPs) were evaluated in a cohort of 140 healthy volunteers. The potentials were induced at the vertex and recorded at the abductor pollicis brevis. The aim of the present investigation was to compare physiological mechanisms which presumably facilitate motor pathways at the cortical level with those known to occur during contraction of small hand muscles. When compared with MEPs at rest, the maximum average decrease of latencies (1.5, SD 1.1 ms) as well as the highest increase of peak to peak amplitudes (2.6, SD 2.1 mV) was observed during exertion of a voluntary background force, at the muscle recorded from. Pre-innervation of a neighbouring muscle (abductor digiti minimi) led to a lesser average decrease of latencies by 1.0, SD 1.1 ms and an average increase of amplitudes by only 0.5, SD 1.5 mV. Non specific manoeuvres, like sticking out the tongue or counting aloud, reduced mean latencies slightly by 0.4 ms, SD 0.8 ms and 0.3 SD 0.85 ms respectively, but increased amplitudes markedly by an average of 1.0, SD 1.6 mV and 0.8, SD 1.4 mV respectively. It is concluded that facilitation of MEPs by non-specific manoeuvres occurs and must be taken into account when evaluating MEPs. PMID- 2273409 TI - Skin and epidural recording of spinal somatosensory evoked potentials following median nerve stimulation: correlation between the absence of spinal N13 and impaired pain sense. AB - A clinical lesion study and intraoperative epidural recordings were made to test the origin and clinical significance of the spinal N13 and P13 of somatosensory evoked potentials (SEP) that follow median nerve stimulation. Intraoperatively, the respective peak latencies of spinal P13 and N13 coincided with those of the N1 component of the dorsal cord potential and its phase reversed positivity. On both the ventral and dorsal sides of the cervical epidural space, maximal amplitude was at the C5 vertebral level to which nerve input from the C6 dermatome is the main contributor. The modality of sensory impairment in the hand dermatome was examined in selected patients with cervical lesions, who showed such normal conventional SEP components as Erb N9, far-field P9, P11, P14, N18 and cortical N20, with or without loss of spinal N13. Statistically, the loss of spinal N13 was associated with decrease of pain sensation in the C6 dermatome. This was interpreted as being due to damage to the central grey matter of the cord, including the dorsal horn. Our results suggest the spinal N13 and P13 originate from the same source in the C6 spinal cord segment and that they are good indicators for the detection of centromedullary cervical cord damage. PMID- 2273411 TI - The development of infratentorial atrophy in patients with idiopathic cerebellar ataxia of late onset: a CT study. AB - The development of infratentorial atrophy in six patients suffering from idiopathic cerebellar ataxia of late onset was studied by a retrospective evaluation of consecutive computed tomography (CT) scans. Four patients had evidence of olivopontocerebellar atrophy (OPCA) both on clinical testing and magnetic resonance imaging (MRI). In these four patients, atrophy of the cerebellum and brain stem became visible at the same time and progressed in a roughly parallel manner, whereas in the remaining two the brain stem was left intact. In all patients with OPCA, definite brain-stem atrophy was visible earlier than the appearance of non-cerebellar clinical symptoms. The present data suggest that CT investigations at regular intervals may be of prognostic value in cerebellar ataxias. PMID- 2273412 TI - Reliability of the clinical and electromyographic examination of tendon reflexes. AB - The reliability of clinical examination of the tendon reflexes was examined by studying inter-observer agreement. Twenty patients were examined by three neurologists. The briskness of the tendon reflexes in arms and legs was scored on a nine-point scale. In 28% of the 160 examined reflexes the observations disagreed 2 scale units or more. Disagreement on the presence of asymmetry occurred in 45% of the 80 reflex pairs. In 15% one observer judged a reflex pair to be symmetrical while another observer found asymmetry of at least 2 scale units. In a second experiment clinical observation of apparently asymmetrical quadriceps reflexes was compared with measurement by surface electromyography. A significant, semi-logarithmic relationship was found between clinical scores and measured reflex amplitudes. Measured reflex asymmetry always agreed with clinical asymmetry, and the magnitudes of right-left amplitude differences were correlated with the magnitude of clinically observed asymmetry. The bedside examination of tendon reflexes is subject to considerable inter-observer disagreement. PMID- 2273415 TI - Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome. AB - Two non-alcoholic homosexual patients with acquired immunodeficiency syndrome (AIDS) are reported who developed acute Wernicke's encephalopathy in the terminal stage of their illness. The first patient presented with vascular congestion, minute haemorrhages, proliferation of microglia and of the vessel walls at the predilection sites of the Wernicke-Korsakoff process. In the second patient only the mamillary bodies were involved. Besides Wernicke's encephalopathy, a primary cerebral immunoblastoma and cerebral toxoplasmosis were found in the first patient, whereas the second showed severe encephalitis with numerous microglial and multinucleated giant cells reacting positively with anti-HIV antibody. Just as in the development of Wernicke's encephalopathy in malignant diseases, the catabolic trend of the metabolism of the immunodeficient patients with consecutive thiamine deficiency must be considered the principal pathogenetic mechanism. PMID- 2273413 TI - Impairment of vertical motion detection and downgaze palsy due to rostral midbrain infarction. AB - We present two cases with acute onset of vertical gaze palsy, mainly consisting of impaired downgaze and apraxia of downward head movements, together with neuropsychological deficits (hypersomnia, impaired attention and disorders of memory and affective control). CT and MRI revealed bilateral post-ischaemic lesions in the dorsomedial thalamus and the mesodiencephalic junction, dorsomedial to the red nucleus, thus being restricted to the territory of the posterior thalamosubthalamic paramedian artery, which includes the region of the rostral interstitial nucleus of the medial longitudinal fascicle as the main premotor nucleus for the generation of vertical saccades. In our patients, oculographic examination with electro-oculography and magnetic search coil recording showed severe impairment of downward more than upward saccades and only minor deficits of vertical pursuit and the vestibulo-ocular reflex. Visual functions were normal, with one exception: a psychophysical test of motion perception revealed a significant deficit in the detection of vertical movements. This could be due to a central adaptive mechanism which, in order to minimize oscillopsia, might elevate thresholds for vertical motion perception in cases of vertical gaze palsy. As an alternative explanation, lesions within the midbrain tegmentum could have damaged subcortical visual pathways involved in motion perception. PMID- 2273414 TI - HLA and multiple sclerosis in Italy: a review of the literature. AB - HLA antigens of locus A, C, B, DR and DQ were typed in 104 Italian multiple sclerosis patients and in 905 healthy controls; the results have been compared with those published in the Italian literature. The Italian studies have been reviewed regarding the ethnic origin of the typed population and the corresponding prevalence of the disease. The data suggest a lack of association between A3 and B7 antigens and Italian multiple sclerosis and a relevance of other DR locus antigens (mainly DR4 and DR5), in addition to DR2, in the susceptibility to the disease. PMID- 2273416 TI - Office management of patients infected with the human immunodeficiency virus (HIV)--1990. AB - Human immunovirus (HIV) infections and related diseases continue to consume a major portion of health care resources nationwide and in the state of Oklahoma. There were 162 new cases of acquired immunodeficiency syndrome (AIDS) diagnosed in Oklahoma in 1989 and an additional 347 cases of other HIV infections were reported. It appears almost certain that few physicians in practice, if any, will escape seeing HIV-related illnesses. It is, therefore, important that all physicians have an adequate understanding of the basic management of these related illnesses. The reader is referred to our original article in the October 1988 issue of the Journal of the Oklahoma State Medical Association, which outlined the office management of HIV-positive patients. The current paper represents an update on this problem. Many of the original tenets and descriptions of management remain the same, and they will not be repeated. PMID- 2273417 TI - High dose rate sources in remote afterloading brachytherapy: implications for intracavitary and interstitial treatment of carcinoma. AB - Remote afterloading brachytherapy provides effective cancer treatment with zero personnel radiation exposure compared to conventional low dose rate systems requiring inpatient use of iridium, radium, or cesium sources. Clinical use of high dose rate brachytherapy is broadened to encompass curative treatment of cervical, endometrial, endobronchial, head and neck, esophageal, rectal, and prostatic carcinomas as well as palliation of intra-abdominal metastasis intraoperatively. Complications encountered with high dose rate sources will be compared to those of low dose rate systems commonly used in conjunction with external beam irradiation. Radiobiological effectiveness and economic benefits will be addressed to provide support for use of remote afterloading using high dose rate brachytherapy in palliative and curative treatment of selected carcinoma. PMID- 2273418 TI - Allied health education in Oklahoma. AB - This article is the first of several dealing with medical education and recruitment in Oklahoma and generated at the request of the OSMA-OUHSC Liaison Committee. The articles were sought out and submitted with the assistance of Edward N. Brandt, Jr., MD, PhD, executive dean at the University of Oklahoma College of Medicine. PMID- 2273419 TI - Leaders in medicine: Joe L. Duer, MD. PMID- 2273420 TI - Shanghai in Oklahoma? PMID- 2273421 TI - Surgical complications of the hemolytic-uremic syndrome. AB - Hemolytic-uremic syndrome (HUS) of childhood is a triad of acute hemolytic anemia, thrombocytopenia, and acute renal failure associated with a gastrointestinal prodrome. From 1977 to 1988, 134 patients with HUS were admitted to this institution. All patients presented with abdominal pain and diarrhea, which was virtually always bloody. Seventy-eight patients (60%) required dialysis. Five patients died (4%). One patient died as a result of colon perforation, the other four patients died of other nonsurgical complications of HUS. Three patients underwent exploratory laparotomy. One patient had a hemoperitoneum from mesenteric and transmural bleeding of the entire intraabdominal colon. Another patient had undergone surgery elsewhere for presumed intussusception with pancolitis found at exploration. Fourteen days postoperatively, he had a spontaneous perforation of the transverse colon. The third patient presented with pancolitis and perforation of the transverse colon. Despite surgical intervention he died on the sixth postoperative day. One other patient was treated conservatively for pancreatitis, which developed 3 weeks after her presentation with HUS. Complications requiring surgical intervention in HUS are rare, potentially lethal, and usually involve the colon. PMID- 2273423 TI - Umbilical fold incision for pyloromyotomy. AB - A 5-year experience with 100 infants undergoing pyloromyotomy was reviewed. Fifty infants who had a standard right upper quadrant incision were compared with 50 infants in whom an umbilical fold incision was used. The groups did not differ significantly with respect to length of operating time, hospital stay, or intraoperative complications. Wound complications were infrequent and minor in both groups. The umbilical fold incision permits excellent access to the pylorus, while leaving an almost undetectable scar. PMID- 2273422 TI - Appendicitis in children: current therapeutic recommendations. AB - Wound infection is the most common source of morbidity in appendicitis. Most recent pediatric series use protocols of preoperative antibiotics with aerobic and anaerobic coverage, intraoperative lavage, no peritoneal or wound drains, and continuation of antibiotics postoperatively with complicated appendicitis. There still remains controversy concerning skin closure and the duration of antibiotic therapy. We report the results of a prospective protocol followed over 2 years with 420 children. The protocol was designed to determine whether the skin could be closed primarily in all patients undergoing appendectomy. Preoperatively all patients received triple antibiotics (ampicillin, gentamicin, and clindamycin) that were continued postoperatively for two doses if there was a normal appendix or simple acute appendicitis, for at least 3 days with gangrenous appendicitis, and at least 5 days with perforated appendicitis. Antibiotics were continued if the patient remained febrile or had a white count greater than 10,000. No drains were used and the skin was closed primarily. The overall infectious complication rate was 1.0% (4/420). Among those with a normal appendix or simple acute appendicitis there were no infectious complications. Among those with gangrenous or perforated appendicitis there were 1.7% wound infections (2/117) and 1.7% intraabdominal abscesses (2/117). Duration of hospitalization was 2.1 days (range, 1 to 5 days) after simple acute appendicitis and 6.9 days (range, 3 to 40 days) after gangrenous or perforated appendicitis. These results set new standards in terms of wound management, infectious complications, and length of hospital stay. PMID- 2273424 TI - Balloon catheter dilatation for hypertrophic pyloric stenosis. AB - Balloon dilating catheters (BDC) have provided a non-operative means of managing obstructive lesions within the gastrointestinal tract. Its potential utility in infants with hypertrophic pyloric stenosis (HPS) was studied. Six patients with HPS underwent balloon catheter dilatation of the pylorus under the direct observation of the surgeon. The pylorus was exposed using a standard right upper quadrant incision. The BDC was passed transorally into the stomach and manipulated into the pyloric canal by the surgeon. The balloon was inflated with saline to a maximum pressure of 50 psi for 2 minutes. Four patients were dilated with a 10-mm diameter balloon catheter, and in two patients, a 15-mm balloon was used. Success was defined as the complete and longitudinal disruption of the seromuscular ring without violation of mucosal integrity. Using this criterion, none had successful pyloric dilatation. No disruption occurred in three patients, partial disruption in two. These patients subsequently underwent a Ramstedt pyloromyotomy. Complete disruption was observed in one; however, a breach of the mucosa was evident. This was repaired without incident. All seromuscular breaks occurred at the point of vascular entry along the lesser curve, presumably the weakest point of the ring. Pyloric dilatation using BDC does not reliably disrupt the muscular ring. This preliminary report recognizes that major refinements must occur before this method will supplant the time-honored surgical pyloromyotomy for HPS. PMID- 2273425 TI - Complications associated with surgical treatment of congenital intrinsic duodenal obstruction. AB - Although survival rates for infants undergoing surgical treatment for congenital intrinsic duodenal obstruction are high, long-term follow-up suggests a high complication rate related to surgical therapy. We reviewed 33 neonates who underwent surgery for congenital intrinsic duodenal obstruction during the past 10 years. There were 20 girls and 13 boys; the mean gestational age was 36 weeks, and mean birthweight was 2,485 g. Bilious vomiting and intestinal obstruction were the most frequent presenting symptoms. Hydramnios was present in 75% of cases and 21% had associated Down's syndrome. Findings at laparotomy included duodenal atresia (14), annular pancreas (11), and duodenal diaphragm (8). The most frequent surgical procedure was side-to-side duodenoduodenostomy (DD), followed by duodenojejunostomy and resection of web with Heineke-Mikulicz type duodenoplasty. Bowel transit was reestablished at a mean of 13.1 days (range, 6 to 45 days). Seventy-percent of patients developed postoperative complications, the most frequent being megaduodenum with blind loop syndrome or bile reflux gastritis (22%), cholestatic jaundice (17%), gastroesophageal reflux (17%), delayed transit (8%), and bowel obstruction (8%). Six patients (18%) required secondary surgical procedures for postoperative complications (ie, megaduodenum, nonfunctioning anastomosis, missed intrinsic stenosis). Two patients died (6%). Stagnation and functional obstruction in the proximal duodenum is the main factor influencing the morbidity rate among these patients. Consideration should be given to the tapering duodenoplasty and diamond-shaped anastomosis in order to help reduce problems associated with megaduodenum and help restore earlier bowel transit. PMID- 2273426 TI - Ultrashort Hirschsprung's disease: myth or reality. AB - The term ultrashort Hirschsprung's disease has been used to define a spectrum of conditions with clinical presentation similar to Hirschsprung's disease but with presence of ganglion cells on rectal biopsy. In contrast to Hirschsprung's disease, there is no transition zone on barium enema. However, as in classical Hirschsprung's disease, there is no reflex internal sphincter relaxation on rectal manometry. We reviewed the presentation of five patients with chronic constipation who fulfilled the criteria for ultrashort Hirschsprung's disease. After positive anorectal manometry, despite the presence of ganglion cells on suction rectal biopsy, internal sphincter myomectomy was performed in four patients. Resolution of symptoms was noted in all operated patients. Normal ganglion cells were present throughout the entire length of all myomectomy specimens. There is controversy in the literature concerning the diagnosis of ultrashort Hirschsprung's disease. Most of the confusion concerns whether a short segment of aganglionosis proximal to the dentate line is permissible for the diagnosis of ultrashort Hirschsprung's disease and to what extent such aganglionosis is physiological. Perhaps it would be more accurate to define this entity by the presence of ganglion cells on rectal biopsy as well as the failure of the internal sphincter to relax on rectal manometry and to describe it as anorectal achalasia in severely constipated patients. PMID- 2273427 TI - Malrotation presenting beyond the neonatal period. AB - The diagnosis of malrotation is easily made in the neonatal period, but is often delayed in older patients. Among 82 patients treated for malrotation in this institution, 45 patients presented with symptoms related to their malrotation, seven were diagnosed at exploration for concomitant intrinsic duodenal obstruction, and 30 patients had malrotations discovered as incidental findings at laparotomy or autopsy. Among the 45 symptomatic patients, 25 (56%) underwent surgery in the first month of life, whereas 20 patients (44%) underwent surgery at an older age. In this last group, the mean age at surgery was 51.5 months (range, 2 months to 16 years), the mean age of onset of symptoms was 2 years (range, 0 to 15 years) and the mean delay in diagnosis was 1.7 years. Although bilious vomiting was the presenting symptom among all patients undergoing surgery in the neonatal period, clinical features of older patients included intestinal obstruction (7), chronic abdominal pain (4), malabsorption/diarrhea (3), peritonitis/septic shock (2), solid food intolerance (1), common bile duct obstruction (1), abdominal distention (1), and delayed transit postappendectomy (1). The frequency of midgut volvulus was equal among both groups. Unusual forms of malrotation were more frequent in patients undergoing surgery beyond the neonatal period. In this group there was evidence of chronic venous and lymphatic obstruction with one case of superior mesenteric vein thrombosis and two cases of intestinal gangrene. A Ladd's procedure was performed in all cases and the most frequent postoperative complication was adhesive intestinal obstruction. There were no deaths. Awareness of the unusual presentation in patients who present beyond the neonatal period may help reduce delays in diagnosis and surgical treatment. We believe that laparotomy is indicated in all patients with malrotation, even if they are asymptomatic. PMID- 2273428 TI - Malignant thymoma in children: a 20-year review. AB - Malignant thymomas are extremely rare in children, with only 27 cases reported thus far in the pediatric surgical literature. We report four additional cases diagnosed at this institution over the past 20 years (ages 3 to 14 years). Clinical presentations included superior vena cava syndrome, cough, dyspnea, cyanosis, enlarging mediastinal mass, spontaneous pneumothorax, and pleuropericardial effusion. Three patients underwent incomplete resection of the mass or biopsy because of "unresectability" and were treated with radiotherapy and adjunctive chemotherapy. One patient underwent near complete macroscopic resection as well as radiotherapy and chemotherapy. All patients died at intervals ranging from 6 months to 2 1/2 years after diagnosis. Three patients were found to have metastatic disease prior to death or at autopsy. In one case, the initial pathological diagnosis was lymphocytic thymoma. After ultrastructural studies were performed, the diagnosis was changed to thymic T-cell lymphoma. This patient subsequently developed acute lymphoblastic leukemia 3 months after surgical resection followed by radiotherapy. Malignant thymomas are highly aggressive tumors in children. A radical surgical approach with complete excision of the tumor and contiguous structures in continuity, with adjunctive radiotherapy and chemotherapy remains the only hope for survival in children with these rare lesions. PMID- 2273429 TI - The effects of talc pleurodesis on growing swine. AB - Talc pleurodesis is an effective means of preventing recurrent pneumothorax. We have successfully applied talc pleurodesis with thoracoscopy in children with cystic fibrosis presenting with pneumothorax. However, little is known about the effects of talc pleurodesis on lung compliance in growing children. Therefore, six young pigs (10 weeks old, weighing 15 +/- 1 kg) were prepared for study. In each pig, one hemithorax underwent thoracoscopy and talc pleurodesis (TALC). The other hemithorax underwent either thoracoscopy alone or no procedure (CONTROL). Dynamic and static respiratory mechanics were studied 5 and 10 weeks later. Air flow and airway pressure were measured to calculate dynamic transpulmonary and transrespiratory compliance, and static transpulmonary compliance. At 5 weeks, dynamic transpulmonary and transrespiratory compliance were less in the TALC lungs when compared with CONTROL lungs. At 10 weeks, the differences in dynamic transpulmonary and transrespiratory compliance between the TALC and CONTROL lungs had resolved. Static compliance was lower in the TALC lungs than in the CONTROL lungs at both 5 and 10 weeks, but this was significant only at 10 weeks. There was an improvement in static compliance in the TALC lungs between 5 and 10 weeks, but this only approached significance. At autopsy, there were marked adhesions and pleural thickening in the talc lungs. Histological examination demonstrated no differences in lung parenchyma between the TALC lungs and the CONTROL lungs. Talc pleurodesis causes a temporary impairment in dynamic transpulmonary and transrespiratory compliance that resolves with time and growth. Static compliance is more persistently compromised, but a trend toward improvement with time and growth exists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273430 TI - Early experience with reduced-size liver transplants. AB - Scarcity of small donors results in a high mortality rate for children on liver transplant waiting lists. To alleviate this problem, we have recently started to reduce the size of livers from older donors to use in children. In the last year, a total of 20 liver transplants were performed in 17 patients, including seven reduced-size liver transplants (RSLT) in six children. Mortality on the waiting list has been reduced to negligible amounts compared with a mortality rate of 25% before starting RSLT in patients with acute liver failure or those whose weight was less than 10 kg. Children undergoing RSLT weighed 10.8 +/- 8.5 kg compared with 20.9 +/- 20.3 for all others (NS). Cold ischemia time was significantly longer in the RSLT group (9.5 +/- 3.0 v 6.0 +/- 2.8 hours, P less than .05) as was intraoperative blood loss (9.4 +/- 9.4 v 3.0 +/- 3.5 blood volumes). There was no significant difference in postoperative aspartate aminotransferase and prothrombin time between the two groups. Four children received a RSLT as a primary procedure and three have survived with good liver function. Two patients were retransplanted with RSLT after a failed first transplant and both died of nonhepatic complications. This compares with 11 of 13 survivors in the whole liver transplant group. Causes of death in children who died after RSLT include cytomegalovirus sepsis (2) and myocardial infarction(1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273431 TI - Pediatric blunt liver injury: establishment of criteria for appropriate management. AB - There is no consensus regarding the most appropriate management of pediatric blunt liver injury. This study addresses this issue by reviewing our experience with blunt liver trauma in relationship to the grade of injury. Forty-one pediatric patients with blunt abdominal trauma and documented liver injury were managed from 1979 to 1989. Fifteen (37%) underwent celiotomy. Three children had extensive parenchymal injuries (grade IV or V) requiring resection and three others died intraoperatively, secondary to exsanguinating hemorrhage of associated injuries (grade V) to the hepatic veins and inferior vena cava. The need for celiotomy was obvious in these patients. In 9 of the 15 children who underwent exploration (60%), bleeding from the liver injury (grade II or III) had ceased by the time of celiotomy. These children did not appear to benefit from the operation. Twenty-six of the 41 patients (63%) were selected for nonoperative management because they were hemodynamically stable after initial resuscitation and did not show signs of associated intraabdominal injuries requiring surgical intervention. These children underwent evaluation by abdominal computed axial tomography scan (grade I, II, III, and IV injuries). Blood transfusions were given to keep the hematocrit above 30%. Seventeen of the 26 children managed nonoperatively (65%) did not require blood replacement. The mean (+/- SEM) transfusion volume for the remaining nine children was 14.8 +/- 2.5 mL/kg. Blunt liver injury represents a spectrum from a minimal parenchymal hematoma to massive liver disruption. We conclude that celiotomy is necessary for hepatic injury hemodynamically stable injured children with transfusion requirements less than 40 mL/kg can be managed nonoperatively in an appropriate setting. PMID- 2273432 TI - Unsuspected diaphragmatic hernia: a potential cause of sudden and unexpected death in infancy and early childhood. AB - Congenital diaphragmatic hernias are usually found in neonates who present with respiratory distress. However, a significant number may remain clinically undiagnosed until much later in life. Of interest, the prognosis is felt to be better in this latter group. We describe three previously well patients (aged 2, 4, and 24 months) who suffered unexpected cardiorespiratory arrests due to unsuspected congenital diaphragmatic defects with intestinal herniation. Deaths resulted from cardiovascular and respiratory compromise due to visceral herniation that caused mediastinal and pulmonary compression. PMID- 2273433 TI - Complications of gastroesophageal antireflux surgery in neurologically impaired versus neurologically normal children. AB - Antireflux surgery was performed in 234 children over a 5-year period; 153 were neurologically impaired (NI) and 81 were neurologically normal (NN). Initial presentation, demographic data, and type of antireflux operation were similar in the two groups. Eighty-six percent of the NI group versus 30% of the NN group had gastrostomy tubes placed. The incidence of late postoperative complications was 26% in the NI group and 12% in the NN group (P less than .01). During the late postoperative period, NI children underwent reoperation four times as frequently as NN children (19% v 5%, respectively; P less than .01). Wrap herniation accounted for 38% of complications and 59% of reoperations in the late postoperative period. Mortality due to aspiration occurred in 9% of the NI group versus 1% of the NN group. Combined failure rate (reoperation plus aspiration induced deaths) was 28% in NI and 6% in NN (P less than .01). We conclude that neurological status is the major predictor of operative success and that wrap herniation due to crural disruption is the most common cause of operative failure. PMID- 2273434 TI - Management of foreign-body bronchial obstruction using endoscopic laser therapy. AB - A case is presented in which the Nd:YAG laser obviated the need for a major thoracic procedure. A 7-year-old boy presented with an 18-month history of persistent nonproductive cough, preceded by a choking spell while eating pistachio nuts. High-grade left mainstem bronchial obstruction was caused by friable granulation tissue secondary to an underlying foreign body. By advancing a laser fiber through the working channel of a 5-mm Storz ventilating bronchoscope, the granulation tissue was vaporized, showing an irregular piece of pistachio nut shell embedded within the bronchial wall. After retrieval of the foreign body, bronchial patency was restored. Recovery was complete and uneventful. The bronchoscopic laser permits the delivery of precise and effective treatment to lesions within confined areas, and has a useful role in the management of some central airway lesions in children. PMID- 2273435 TI - Delayed presentation of Hirschsprung's disease: acute obstruction secondary to megacolon with transverse colonic volvulus. AB - Despite advances in the diagnosis of Hirschsprung's disease, occasionally there is still a delay in presentation. We report an unrecognized case of Hirschsprung's disease in a patient who presented at 11 years of age with volvulus of the transverse colon. This is the eighth reported case of colonic volvulus secondary to Hirschsprung's disease in children and the first occurring in the transverse colon. A literature review of other causes of colonic volvulus in children showed only 31 cases occurring in the sigmoid colon and nine in the transverse colon. The treatment of unsuspected colonic volvulus in children is discussed. PMID- 2273436 TI - Perforation of the colon in a 15-year-old girl with Ehlers-Danlos syndrome type IV. AB - A 15-year-old girl presented with severe fecal peritonitis due to a large spontaneous colonic perforation. The sigmoid colon was the site of a cluster of white serosal lesions with omental adhesions, of an appearance identical to that of the edges of the perforation. Her father had died at 30 years of age of spontaneous rupture of an iliac artery aneurysm, preceded by rupture of a splenic artery aneurysm and a spontaneous carotid-cavernous fistula. The clinical diagnosis of Ehlers-Danlos syndrome type IV was made, and confirmed by demonstrating that the patient's cultured fibroblasts are not producing or secreting type III collagen. Spontaneous perforation of the colon is a well described complication of this syndrome, with a high incidence of recurrence. We recommend total abdominal colectomy to minimize the latter possibility. PMID- 2273437 TI - Management of chylopericardium. AB - Chylopericardium is a rare entity that may be congenital in origin or secondary to surgical trauma, mediastinal lymphangiomas-hygromas, or radiation. Current treatment progresses from dietary medium-chain triglycerides and pericardiocentesis, to pericardial drainage, to thoracotomy with pericardiectomy and thoracic duct ligation. Between January 1986 and January 1989, we treated four children with chylopericardium: three secondary to mediastinal lymphangioma hygroma, and one following cardiac surgery. The patients ranged in age from newborn to 16 years. All had signs of cardiac tamponade and three underwent initial pericardiocentesis or tube drainage. One 6-week-old infant with a mediastinal cystic hygroma developed chylopericardium following resection of the hygroma and responded to 9 days of tube drainage. The remaining children did not respond to repeated pericardiocenteses or prolonged drainage and underwent pericardial-peritoneal shunting with Denver shunts. The shunt was removed in 14 days in one patient. One patient had the shunt exteriorized for 8 weeks and one patient continues to use the shunt after 3 years. The chylopericardium resolved in each case without recurrence. Pericardial-peritoneal shunting provides a simple and effective alternative to prolonged pericardial drainage or thoracotomy in patients with chylopericardium of various etiologies. PMID- 2273438 TI - A 24-year follow-up of a large omphalocele: from Silon pouch to pregnancy. AB - In 1970, this patient was first reported after her massive ventral hernia was repaired. Her large omphalocele was initially covered with skin flaps as a newborn, and at 3 years of age the resulting ventral hernia was completely repaired using the staging technique described by Schuster, and modified by Plzak and Gross. Silon sheeting was used as a temporary prosthesis. She remained well until 1988 (age 23 years) when she became pregnant with the expected date of confinement January 10, 1989. The first two trimesters were uneventful with sonograms showing a normal male fetus who was gaining weight appropriately. By the third trimester the abdominal girth did not increase coincident with the baby's size, vomiting prevented adequate caloric intake, and pelvic pressure from the baby's head caused increasing discomfort. She spent 7 weeks in the hospital on intravenous therapy, including peripheral total parenteral nutrition, and delivered vaginally, with the aid of forceps, a 2.9-kg normal boy 5 weeks prematurely. This is the first reported case of a large omphalocele patient conceiving and delivering a normal fetus. It also demonstrates the potential problems related to multiple surgical procedures to close a large congenital abdominal wall defect. PMID- 2273439 TI - Postoperative intussusception in a premature infant. AB - Intussusception occurs most commonly between the fifth and ninth month of life. Affected infants are usually healthy and born at full gestation age. We describe a case of intussusception occurring in a 10-day-old, 700-g neonate born at 28 weeks' gestation. The diagnosis was made at laparotomy 7 days after colostomy for imperforate anus. There were three associated bowel perforations. This case demonstrates that postoperative intussusception can occur in the premature infant. It also serves to illustrate the difficulty in making the diagnosis preoperatively. PMID- 2273440 TI - Aberrant cervical thymus in children: three case reports and review of the literature. AB - Aberrant migration of thymic tissue occurs with ectopic thymus in the mediastinum, base of the skull, tracheal bifurcation, and cervical region. A recent review of the literature showed a total of 76 reported cases of aberrant thymus or thymic cysts in patients who presented with primary neck masses. We report three additional cases of ectopic cervical thymus. All three patients presented with asymptomatic cervical masses, and preoperative diagnosis included branchial cleft cyst, cervical lymphangioma, and cervical teratoma. All patients underwent complete surgical resection of the masses. Aberrant cervical thymus rarely produces symptoms because it does not invade contiguous strictures. Despite its rarity, it should be considered in the differential diagnosis of asymptomatic neck masses in children. PMID- 2273441 TI - An unusual intraoral mass in a child: the organ of Chievitz. AB - A 5-year-old girl presented with a hard, asymptomatic, fixed mass protruding intraorally at the level of the ascending ramus of the mandible on the right. Plain roentgenograms of the jaw, panorex, computed tomography scan, and magnetic resonance scan of the area failed to demonstrate any lesion. An incisional biopsy showed neuroectodermal tissue with a pattern characteristic of the juxtaoral organ of Chievitz. At 2 years follow-up, the residual mass remains the same. The organ of Chievitz is a normal structure that can be frequently identified at routine autopsy if sought for, but is seldom large enough to present as a mass. A conservative biopsy without further treatment is recommended when the clinical diagnosis is in doubt. PMID- 2273442 TI - Effect of food on the bioavailability of bromazepam following oral administration in healthy volunteers. AB - The effect of food on the rate and extent of bioavailability of bromazepam was examined in seven normal volunteers following a single oral dose of 10 mg bromazepam with 200 ml of water in the fasting and non-fasting states. Plasma concentrations of bromazepam were measured by high pressure liquid chromatography. A tmax value in a non-fasting state was prolonged from 2.3 +/- 0.3 (mean +/- S.E.M.) to 2.8 +/- 0.6 h but not significantly different (p greater than 0.05) whereas a Cmax value was significantly (p less than 0.05) decreased from 259 +/- 12.7 (mean +/- S.E.M.) to 169 +/- 13.9 ng/ml. The area under the plasma concentration-time curve in the non-fasting state was also significantly (p less than 0.05) decreased from 1844 +/- 145 (mean +/- S.E.M.) to 1233 +/- 98.1 ng.h/ml after oral administration of bromazepam. PMID- 2273443 TI - Effects of sulfur-containing metabolites of hexachlorobenzene on the heme metabolic enzymes in rat liver. AB - Effects of hexachlorobenzene (HCB) and its sulfur-containing metabolites on the heme metabolic enzymes in rat liver were investigated. A single injection of HCB caused the increase in activities of delta-aminolevulinic acid (ALA) synthetase and heme oxygenase, and contents of cytochrome P-450 and total heme. After a single injection of pentachlorothioanisol (PCTA) or pentachlorophenyl methyl sulfore (PCPSO2Me), ALA synthetase activity was enhanced. Heme oxygenase activity was increased by PCPSO2Me treatment. Cytochrome P-450 and total heme contents were increased by PCPSO2Me or 1,4-bis(methylthio)tetrachlorobenzene (MTTCB). When HCB was injected once daily for 5 weeks, a marked increase in ALA synthetase activity, a significant decrease in ALA dehydratase, almost complete inhibition of uroporphyrinogen decarboxylase activity, and an increased excretion of total porphyrin in the urine were shown. After chronic treatment with its sulfur containing compounds, PCPSO2Me and MTTCB produced a significant increase in ALA synthetase activity. However, activities of ALA dehydratase and uroporphyrinogen decarboxylase, and excretion of total porphyrin in the urine were unaltered. At this time, the concentrations of the corresponding sulfur-containing compound and related metabolite(s) in blood, liver and kidney were nearly the same as those observed in HCB-treated rats. It is suggested that PCPSO2Me and MTTCB could induce the hepatic ALA synthetase, but, these metabolites, and also PCTA, were not able to induce the porphyria in female rats, and the induction of porphyria by HCB is not attributable to the action of its sulfur-containing compound. PMID- 2273444 TI - The uptake of manganese induced by agonists in the isolated vas deferens of the guinea pig. AB - The uptake of manganese (Mn) induced by 100 mM potassium (K), 10 microM norepinephrine (NE) or 10 microM acetylcholine (ACh) was measured by atomic absorption spectroscopy in isolated vas deferens of the guinea pig. The agonists at these concentrations caused the maximal contraction of the vas deferens. The contents of Mn were increased with the repetitive treatments of Mn with K and were not significantly decreased after 1 h washing. The uptake of Mn was also stimulated by NE and ACh. The stimulation of uptake of Mn by K was the most potent while that by ACh was the smallest. The uptake of Mn was enhanced by elimination of Ca from the medium, while inhibited by the higher concentration of external Ca and by 2.1 microM diltiazem. The time course of K-induced Mn uptake was biphasic: an initial faster phase and a following slower phase of accumulation. The extents of increments of the Mn contents were dependent on the order of the applications of K and Mn: the increments became smaller in the following order, 1) when Mn was applied prior to K, 2) Mn was applied simultaneously with K, 3) Mn was applied after K. These results suggested that superficially bound Mn penetrates into the smooth muscle cells of vas deferens during the stimulation by agonists through the voltage-dependent calcium-channel (VDC) and that intracellular Mn was hardly extruded. It was also suggested that the degree of activation of VDC, through which Mn can enter the cells, was in the following order, K greater than NE greater than ACh. These results were consistent with our previous report about the dual effects of Mn: the inhibition and potentiation of contractions. It was also suggested that Mn may be a useful tool as a Ca analogue because Mn can penetrate into cells through VDC and, once taken up into the cells, Mn is not readily extruded and remains in the cells even after extracellular Mn is washed away. PMID- 2273445 TI - Sodium and pH dependent carrier-mediated transport of antibiotic, fosfomycin, in the rat intestinal brush-border membrane. AB - The mechanism of intestinal absorption of an antimicrobial agent, fosfomycin (FOM), was investigated in rats using small intestinal brush-border membrane vesicles (BBMV). The uptake of [3H]FOM by BBMV was osmolarity- and temperature sensitive and showed apparently saturable uptake kinetics consistent with the Michaelis-Menten equation, having Kt = 15.3 mM and Jmax = 7.78 nmol/30 s/mg protein at 37 degrees C. An overshoot uptake of FOM was observed in the presence of an inwardly direct Na+ gradient. The replacement of extravesicular Na+ with choline or mannitol significantly reduced the uptake. An addition of a protonophore, FCCP, significantly decreased the initial uptake of FOM in the absence of Na+ gradient but in the presence of a H+ gradient (pHin = 7.5, pHout = 6.0), whereas in the absence of a H+ gradient no significant difference was observed between the uptakes at an acidic pH (pHin = pHout = 6.0) and a neutral pH (pHin = pHout = 7.5). An inside negative potassium diffusion potential induced by valinomycin enhanced significantly the uptake of FOM. The uptake of FOM in the presence of both Na(+)- and H(+)-gradients was significantly inhibited by phosphate, arsenate and phosphonoformic acid (PFA), which are specific inhibitors of phosphate transport, but not by D-glucose. Based on these results, it is concluded that FOM transport in the small intestine is partially shared with the Na(+)-phosphate cotransport system and in part occurs via a H(+)-gradient dependent carrier-mediated system. PMID- 2273446 TI - Carrier-mediated uptake of nicotinic acid by rat intestinal brush-border membrane vesicles and relation to monocarboxylic acid transport. AB - The intestinal transport of [14C]nicotinic acid was investigated at 27 degrees C by using brush-border membrane vesicles (BBMV) isolated from the rat small intestine. The osmolarity sensitive uptake by BBMV showed a remarkable overshoot phenomenon in the presence of an inward-directed H+ gradient (pHin = 7.5, pHout = 6.0). In contrast, the imposition of a Na+ gradient ([Na+]in = 0 mM, [Na+]out = 100 mM) had no stimulatory effect on the uptake of [14C]nicotinic acid. The remarkable pH-dependence of the initial uptake showing an increase of the uptake rate with decreasing the extravesicular pH disappeared completely in the presence of a structural analogue, isonicotinic acid, at pH below 6.5. In the presence of a H+ gradient, the initial uptake of [14C]nicotinic acid was saturable with the apparent Kt of 4.43 mM and Jmax of 2.55 nmol/mg protein/15 s. The uptake was increased by the imposition of an inside-positive membrane potential and was significantly inhibited by monocarboxylic acids such as benzoic acid, salicylic acid, acetic acid, propionic acid, valproic acid and L-lactic acids as well as two isomers (isonicotinic acid and picolinic acid). The uptake was not inhibited by nicotinamide, nicotinyl alcohol, D-glucose, p-aminohippuric acid, glycyl-L proline, succinic acid and an exchange transport inhibitor. From these results it was concluded that nicotinic acid is transported through the intestinal brush border membrane by a carrier-mediated system and the system can recognize some acidic drugs with a monocarboxylic group. The pH dependent intestinal uptake of nicotinic acid can be ascribed to the proton-coupled and active carrier-mediated transport mechanism rather than a simple diffusion of the undissociated nicotinic acid to follow a pH-partition hypothesis. PMID- 2273448 TI - Inhibition of [3H]glutamate release by Zn2+ in rat hippocampal slices. AB - Zn2+ at the concentration of 10 microM inhibited the depolarization-induced [3H]glutamate release from the preloaded rat hippocampal slices both in the presence and absence of Ca2+ without affecting [3H]GABA and [3H]ACh release. Of divalent cations tested, Zn2+ and Fe2+ had an inhibitory effect on the release of glutamate. PMID- 2273447 TI - Cross-antigenicity between penams and cephems by intradermal skin test and leucocyte migration test in guinea pigs. AB - The delayed-type hypersensitivity (DTH) reactions for penams or cephems of beta lactam antibiotics were investigated by intradermal skin test and leucocyte migration test (LMT) in guinea pigs. The animals were immunized with ampicillin (ABPC) or cephalexin (CEX) using Freund's complete adjuvant. The cross reactivities among ABPC, penicillin G (PCG) and cloxacillin as penam and CEX, cephalothin (CET) and cephalosporin C (CEPC) as cephem and phenylglycine (PhGly), which is the amino acyl side chain of ABPC and CEX, were examined. By intradermal reaction, ABPC-sensitized animals showed a cross-reaction with CEX, PCG and CET, but CEX-sensitized animals did not cause cross-reaction with ABPC. The CEX sensitized group exhibited slight cross-reactions to CET and PhGly. PhGly exhibited low immunogenicity only in maximization test of guinea pig. The above results indicate that there is the difference in cross-reactivity between penams and cephems in skin test. In LMT, all the ABPC-sensitized animals reacted with ABPC and showed cross-reactions with all drugs tested. The CEX-sensitized group reacted with 4 out of 7 animals with CEX and exhibited cross-reactivities to ABPC, PCG, CET, CEPC and PhGly. The cross-reactivity between intradermal skin reaction and LMT elicited some different results. PMID- 2273449 TI - [Stereoselective synthesis of macrolide and polyether antibiotics]. AB - In order to establish a common methodology for the highly stereoselective and efficient synthesis of macrolide and polyether antibiotics, two macrolide aglycons, 12-membered ring methynolide and 16-membered ring tylonolide, were first synthesized mainly from D-glucose, with the aid of 4-methoxybenzyl (MPM) type protecting groups and construction of three consecutive chiral centers, via the syntheses of respective fragments followed by their coupling (Yamaguchi's esterification) and cyclization (Wittig-Horner reaction). This method was extended to the synthesis of 14-membered ring pikronolide and, together with conformational analysis and control of macrolide rings, some typical 16-membered ring aglycons such as carbonolides, leuconolides, maridonolides, etc. Erythronolide A was also synthesized via an extremely efficient macrolactonization by virtue of conformational control and super activation of a seco-acid. For the synthesis of polyether antibiotics a new synthetic method of substituted tetrahydrofuran and -pyran rings was first established via a cyclization of styryl derivatives by acid catalyzed and/or chelation controlled reactions under kinetic and/or thermodynamic conditions. Highly complex polyether salinomycin was synthesized via coupling of three fragments prepared from D glucose, D-mannitol, and ethyl L-lactate essentially by the same method developed in the synthesis of macrolides. In this synthesis the MPM type protecting groups acted a crucial role. The synthesis of isolasalocid A was completed via isolasalocid ketone, in which two tetrahydrofuran rings were constructed by the above acid catalyzed and chelation controlled cyclizations. Similarly lasalocid A was synthesized from D-glucose via lasalocid ketone. PMID- 2273450 TI - [Application of 13C label-nuclear magnetic resonance (NMR) tracer techniques to clinical chemistry. Metabolic rate of benzoic acid to hippuric acid]. AB - A new tracer technique, in which a 13C-labeled compound as a biological tracer and 13C nuclear magnetic resonance (NMR) as an analytical tool are used, is proposed. In order to verify the applicability of the method to clinical chemistry. [1-13C]benzoic acid was administered and [1'-13C]hippuric acid excreted in the urine was quantitated by NMR, by using [1-13C]hippuric acid as an internal standard. PMID- 2273451 TI - [Effects of bile and meal on the gastrointestinal absorption of 2-[3-(3,5-di-tert butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin- 1-yl]ethyl acetate, a new non steroidal anti-inflammatory agent]. AB - The effects of bile and meal on the gastrointestinal absorption of 2-[3-(3,5-di tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin - 1-yl]ethyl acetate (1), were investigated in rats and dogs. Compound 1 was lipophilic and soluble in bile, but extremely insoluble in water. The important role of bile in the dissolution step in the absorption process of 1 was confirmed on the in situ absorption study with rats. Oral absorption of 1 was insufficient and showed a marked individual difference in fasting dogs. When the same compound was administered after ingestion of a meal, the absorption increased with decreasing scatter. Three kinds of meals had different potencies to enhance the bio availability of 1 in the order of lard greater than mashed potatoes greater than skimmed milk. The absorption behavior of 1 reflected small intestinal transit time and the stimulated bile output after ingestion of meal. PMID- 2273452 TI - [Pharmacological studies on puerariae flos. II. The effects of puerariae flos on alcohol-induced unusual metabolism and experimental liver injury in mice]. AB - The present study was designed to examine the effects of methanolic extract (PE ME), isoflavonoid fraction (PF-IF), triterpenoid saponin fraction (PF-SP) and N acyl-N1-glucosyl-tryptophan (PF-P) isolated from puerariae flos on alcohol induced unusual metabolism (as for glucose (BG), triglyceride (TG), and urea nitrogen (BUN) level in blood) and experimental liver injury (model: CCl4- and high fatty food induced) in mice. These alcohol-induced increasing responses were inhibited by the extracted and refined substances from puerariae flos. In short, PF-ME (4500 mg/kg) and PF-P (400 mg/kg) inhibited an increase in BG level induced by alcohol, whereas PF-IF (1000 mg/kg) and PF-SP (1000 mg/kg) did not. Similary, PF-ME and PF-SP inhibited an increase in TG induced by alcohol, whereas PF-IF did not. In addition, PF-IF and PF-SP inhibited increasing BUN level. Still more, PF IF and PF-SP significantly inhibited an increase in gulutamate oxalacetate transaminase or gulutamate pyruvate transaminase level induced by high-fatty food and CCl4 in control animals. Especially PF-IF (250 mg/kg) administration showed a remarkable effect (inhibition: 76.3%) in control animals. These results suggested that puerariae flos or its combination drugs may be a useful drug as a traditional medicinal system for counteraction to drinking. PMID- 2273453 TI - [Changes in lipid peroxides content and antioxidant enzyme activities on airway surface in SO2-induced bronchitic rats]. AB - The changes in lipid peroxides (LP) content and antioxidant enzyme activities were investigated on airway surface during the aggravating process of bronchitis induced by SO2 exposure in rats. LP content in broncho-alveolar lavage fluid (BALF) has gradually increased from 3 weeks after starting of SO2 exposure. Whereas, the activities of antioxidant enzymes, superoxide dismutase and glutathione peroxidase, increased at 1 week and then gradually reduced from 3 weeks. The ratio of LP to each antioxidant enzyme activity in BALF of the exposed rats was higher than that of normal rats. Morphological changes of the lung, a decrease of PaO2 and an increase of PaCO2 of blood depended on the increase of LP on airway surface. These findings indicate that LP may be involved in the development of bronchitis. PMID- 2273454 TI - In vitro release kinetic pattern of indomethacin from poly(D,L-lactide) nanocapsules. AB - Indomethacin nanocapsules were prepared by interfacial deposition of poly(D,L lactide) polymer following displacement of acetone from a lipophilic phase to an aqueous phase. Highly solvated bilayers of phospholipids in excess in the formulation were formed and easily detected by TEM. In vitro release kinetic analysis of indomethacin from pure nanocapsules prepared with poloxamer as sole emulsifier, mixed colloidal suspension (nanocapsules and liposomal vesicules), and multiamellar phospholipidic bilayers revealed that drug release in phosphate buffer sink solution was drastically delayed and incomplete as a result of the high indomethacin solubility in the oily core, poloxamer micelles, and phospholipidic bilayers, respectively. The release process was thus dependent on drug partition from the colloidal suspension phases to the external sink solution. However, addition of albumin to the sink solution markedly enhanced the indomethacin release due to protein binding affinity. A kinetic model equation dealing with biphasic systems in which a drug is dissolved or partitioned between the lipophilic and hydrophilic phases of a dispersed system is proposed and found suitable for the description of indomethacin release from the mixed colloidal suspension only. PMID- 2273455 TI - Mechanism of nasal absorption of drugs. IV: Plasma levels of radioactivity following intranasal administration of [3H]leucine enkephalin. AB - To study the factors influencing nasal absorption of a model pentapeptide, plasma levels of total radioactivity were determined following the administration of [3H]tyr-leucine enkephalin to rats intravenously, intranasally alone, and intranasally in the presence of puromycin. The major pathway for transport of radioactivity into the blood from the nasal cavity appeared to be hydrolysis of [3H]tyr-leucine enkephalin to [3H]L-tyrosine, followed by absorption of [3H]L tyrosine. When puromycin was added to the nasal solution in concentrations at which the in vitro hydrolysis of leucine enkephalin was completely inhibited, the appearance of radioactivity in the plasma was slowed, but plasma concentrations of radioactivity eventually reached levels comparable to those observed in the absence of puromycin. In view of the inhibitory effect of puromycin on the hydrolysis of leucine enkephalin, it was assumed that a significant fraction of the [3H]tyr-leucine enkephalin was absorbed intact in the presence of this substance. However, an assay method for intact leucine enkephalin in plasma is needed to confirm these preliminary observations. PMID- 2273456 TI - Nasal administration of a cognition enhancer provides improved bioavailability but not enhanced brain delivery. AB - Compound 1 [3,3-bis(4-pyridylmethyl)-1-phenylindolin-2-one] is an experimental cognition-enhancing drug now being developed for cognitive disorders. Oral bioavailability of 1 in rats was less than 10% of the dose. Nasal dosing improved bioavailability to greater than 50%. Brain levels of total radioactivity were measured after iv and nasal doses of radiolabeled 1. The ratio of AUCbrain:AUCplasma was the same by both routes, so nasal dosing did not enhance brain delivery. This is in contrast to other reports of large molecular weight substances and metals gaining direct access to the brain through the nasal epithelium. PMID- 2273457 TI - Effect of organic cosolvent-induced skeletal muscle damage on the bioavailability of intramuscular [14C]diazepam. AB - Organic cosolvents are used in many intramuscular formulations for solubilization of drugs and have been shown to cause skeletal muscle damage (myotoxicity). This study explored the influence of organic cosolvent-induced myotoxicity on the bioavailability of a model compound, diazepam. A tracer (C14) dose of diazepam was selected which did not elicit any systemic pharmacologic effects (viz., hypothermia and sedation) that might alter the pharmacokinetics of the drug. Male New Zealand White rabbits were injected with diazepam dissolved in three cosolvent: water mixtures (20% v/v propylene glycol, 20% v/v polyethylene glycol 400, and 50% v/v polyethylene glycol 400). These mixtures have similar physicochemical properties, but vary 10-fold in their in vitro myotoxicity. Using plasma total radioactivity following intramuscular administration of diazepam, statistical differences were not detected in the area under the curve (AUC), the peak concentration, and the time of the observed peak concentration among these treatments, although the in vivo myotoxicity of these systems (measured by the plasma creatine kinase AUC) varied by 10-fold (p less than 0.01). Limited data on unchanged diazepam levels confirmed these observations. Thus, the degree of skeletal muscle damage caused by these organic cosolvent systems does not seem to affect the bioavailability of a tracer dose of intramuscular diazepam. PMID- 2273458 TI - Marked heterogeneity in the intrahepatic distribution of quinidine in rats: implications in pharmacokinetics. AB - Approximately 20 to 24 samples (0.1-0.2 g each) were obtained from each of six isolated rat livers following steady-state infusion of quinidine. The concentrations of quinidine, analyzed by an HPLC method, were found to vary markedly within each lobe (up to approximately 52-fold) or between lobes (up to approximately 25-fold) from the same liver. The maximum intrahepatic concentration difference in the six livers studied was 208-fold. Implications of the present study in the determination of liver drug concentration, and of the partition coefficient between liver and venous drug concentration in physiological pharmacokinetic modeling, as well as in hepatic modeling, are discussed. PMID- 2273459 TI - Effect of aspirin and sulindac on methotrexate clearance. AB - The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7 hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX. PMID- 2273460 TI - Physicochemical properties of carbovir, a potential anti-HIV agent. AB - (+-)-Carbovir [(+-)-9-[4 alpha-(hydroxymethyl)-cyclopent-2-ene-1 alpha yl]guanine; NSC 614846] is a novel carbocyclic nucleoside analogue which has been shown to be a potent and selective inhibitor of HIV in vitro. As part of an effort to develop a parenteral formulation for subsequent clinical and toxicological evaluation of this compound, the aqueous solution stability of carbovir as a function of pH and temperature and various physicochemical properties of carbovir including its pKa, solubility versus pH and solvent composition, and octanol-water partition coefficient have been examined. Ultraviolet spectrophotometry indicated that carbovir has pKa values of 3.15 and 9.68, respectively, at 25 degrees C and 0.01 ionic strength. The aqueous solubility of carbovir over the pH range 7-10.5 was consistent with that expected of a weak acid with a pKa of 9.65 and an intrinsic solubility of 1.24 mg/mL. Due to the limited solubility of carbovir at physiological pH, methods for solubilizing carbovir in aqueous solution were explored, including propylene glycol-water cosolvents and complexation with hydroxypropyl-beta-cyclodextrin. As expected for carbovir, a semipolar compound with an octanol-water partition coefficient of 0.29, propylene glycol:water cosolvents were not highly effective in enhancing solubility. Complex formation between carbovir and 2-hydroxypropyl beta-cyclodextrin was found to be more effective, with a K1:1 of 105 M-1 for the complexation. The pH profiles generated at 50, 70, and 90 degrees C were accounted for by acid-catalyzed degradation at low pH leading to the formation of guanine and a neutral degradation pathway which dominates above pH 4. Prototype lyophilized formulations containing (after reconstitution) 10 mg/mL of carbovir at a pH of 10.6 were developed and evaluated. PMID- 2273461 TI - Drug assay in ground tissues: example of ketoprofen diffusion into tonsillar tissue. AB - Ketoprofen was assayed in tissues of surgical patients after mechanical grinding of the tissue in liquid nitrogen; the fine powder obtained allowed the drug to be determined by HPLC in the same way as for liquid samples. The method was applied to the study of ketoprofen diffusion into the tonsillar tissue of 15 patients after a single intramuscular injection of ketoprofen (100 mg). A correction was made for blood contamination after hemoglobin determination. PMID- 2273462 TI - Pharmacokinetics of physostigmine intramuscularly administered to guinea pigs. AB - Physostigmine pharmacokinetics was determined in guinea pigs following im administration of 5-146 micrograms/kg. Eighteen male guinea pigs were divided into three equal groups and given dosages of 5, 27, and 146 micrograms/kg, respectively. Physostigmine was given in the right hind limb and blood samples were collected at various times up to 300 min postinjection via an indwelling carotid catheter. Unbound physostigmine plasma concentrations were analyzed by HPLC. The concentration-time profile for each animal was fitted to standard pharmacokinetic models. A one-compartment open model with first-order absorption and elimination provided the best fit. For all dosage groups, physostigmine concentrations peaked in approximately 30 min. Apparent volumes of distribution (assuming 100% bioavailability) ranged from 1.9 to 2.2 L/kg. Systemic clearances and elimination half-lives were 30-36 mL/min/kg and 40-50 min, respectively. The area under the concentration-time curve and the Cmax were linearly related to the dose, indicating pharmacokinetic linearity. In conclusion, physostigmine, intramuscularly administered to the guinea pig, is absorbed, distributed, and eliminated rapidly, and the pharmacokinetics behave linearly within the 5-146 micrograms/kg dosage range. PMID- 2273463 TI - Nonlinear estimation of kinetic parameters for solid-state hydrolysis of water soluble drugs. II: Rational presentation mode below the critical moisture content. AB - A logical presentation mode for accelerated data obtained at low relative humidities has been developed. A model is proposed leading to an equation relating the percent decomposition, x, at time t, to the temperature (T, K), and the water vapor (P, mmHg) in an open system. The data presented support the equation. PMID- 2273464 TI - Synthesis and mechanisms of decomposition of some cephalosporin prodrugs. AB - The delta-3 and delta-2 methyl esters of cefazolin were synthesized. The kinetics and mechanisms of degradation of the methyl esters and the delta-3 and delta-2 isomers of pivaloyloxymethyl prodrug esters of the new cephalosporin ceftetrame (Ro 19-5247) were investigated in buffer systems and in human plasma in vitro. The major hydrolytic products of all the delta-3 and delta-2 esters were the inactive delta-2 cephalosporin free acids. The following reaction scheme describes the in vitro hydrolysis of these compounds: [formula: see text]. In addition, there was evidence of opening of the beta-lactam ring to form cephalosporoic acid when the methyl ester of cefazolin was studied in human plasma and in the presence of penicillinase. For the methyl esters, the processes represented by k12, k21, and k20 were operative in buffers; in human plasma, the processes represented by k12, k21, and k20 were operative in addition to cephalosporoic acid formation. For the isomers of the cephalosporin prodrug ester Ro 19-5248 only k12 and k20 were operative in buffers; in human plasma all pathways were operative and there was no evidence of cephalosporoic acid formation. In all cases, the processes represented by k12, k21, and k20 were subject to general and/or specific base catalysis. PMID- 2273465 TI - Release of highly water-soluble medicinal compounds from inert, heterogeneous matrixes. I: Physical mixture. AB - The release from a matrix compressed from a physical mixture of hydrogenated castor oil and ephedrine hydrochloride or procaine hydrochloride has been investigated. The effects on release of the concentration of medicinal compound, particle size of medicinal compound, agitation of dissolution medium, and porosity and tortuosity of the matrix are presented. An attempt is made to fit the experimental data to an acceptable diffusion model. PMID- 2273466 TI - Physical and chemical factors influencing the release of drugs from acrylic resin films. AB - An investigation was conducted to evaluate the factors influencing the release of salicylic acid and chlorpheniramine maleate from polymethacrylate amino-ester copolymer films (Eudragits RL PM and RS PM). Differential scanning calorimetry was performed on the films to study the solubility of drug in the polymer and to determine the effect of added drug on the thermal properties of the film. Incorporation of drug into the polymers decreased the glass transition temperature of the polymers. Dissolution of drug from monolithic slabs was followed as a function of temperature, drug concentration in the films, and ionic strength of the release media. In addition, adsorption studies were conducted with each drug:polymer combination to help explain release results and further characterize the drug:polymer interactions that occurred. The rate of drug release increased with increasing temperature. Adsorption of salicylic acid by the polymers was believed to influence the drug release profiles observed for different drug loadings and ionic strengths. Eudragit RL was found to adsorb salicylic acid to a greater extent than the Eudragit RS. Chlorpheniramine maleate was not found to be adsorbed by either polymer. PMID- 2273467 TI - Study of the relationship between nitrogen basicity and receptor affinity in a substituted quinoline series. AB - In buffered water:methanol media, the pKa values of acid-base equilibria involved in the protonation of substituted quinolines are determined by UV-visible absorption spectrometry. The observed behavior depends on the nature of R2: the N CH3 derivatives exist as quinoline, the N-H derivatives as 4-iminoquinoline tautomers. The iminoquinoline zwitterionic species present at physiological pH may have high receptor affinity. A linear relationship between pKa of the endocyclic nitrogen and log IC50 is discussed. PMID- 2273468 TI - Tetrazoles as carboxylic acid surrogates in the suosan sweetener series. AB - The structure-activity relationship (SAR) in the suosan series of sweeteners has been extended to include additional replacements for the carboxyl group. Tetrazole analogues have been prepared and were found to be sweet. However, both the urea and thiourea tetrazolyl analogues exhibited reduced potency when compared with the carboxyl compounds. Because of the larger size of tetrazole compared with carboxylic acid, chain-shortened tetrazolyl analogues were prepared and found to not be sweet. Some important aspects about the requirements for promoting a sweet taste in vivo can be gleaned from these results. The importance of the degree of delocalization and the orientation of charge density in the anionic group are discussed. PMID- 2273469 TI - Drug partitioning and release characteristics of tricyclic antidepressant drugs using a series of related hydrophilic-hydrophobic copolymers. AB - A series of crosslinked polymer networks formed from hydrophilic polyethylene oxide (PEO) and a hydrophobic polysiloxane (PGPMDMS) were studied with respect to the partitioning and release of five tricyclic antidepressants (TCAs) at pH 7.4. The TCAs, chemical analogues of one another, have both nonpolar and ionic characteristics at pH 7.4, but differ considerably in hydrophobicity. In PEO PGPMDMS copolymer networks, the partition coefficient of protriptyline (the TCA studied most extensively) was observed to be higher than in networks of PEO or PGPMDMS singly. This finding, which may represent adsorption of the amphiphilic drug at interfacial sites between hydrophilic and hydrophobic phases within the copolymeric network, shows that in some cases, higher drug loadings of amphiphilic drugs can be obtained with a hydrophilic-hydrophobic copolymer compared with a material made of only one polymer. As the PEO content in PEO PGPMDMS networks was increased from 20 to 100%, the release rate of protriptyline increased by greater than 1000-fold. Thus, a key variable in achieving a desired release rate is the PEO content of the copolymer. On the other hand, release rates of the five TCAs from PEO-PGPMDMS networks containing 50% PEO varied by a factor of less than 3. Thus, minimal effect on drug release rates was obtained by using a different TCA analogue. PMID- 2273470 TI - Development of oral liquid dosage forms of acetazolamide. AB - Two oral liquid dosage forms of acetazolamide have been developed. Using the solubility profiles, polyethylene glycol 400 (7%, v/v) was used as the solubilizing agent and propylene glycol (53%, v/v) as the cosolvent to keep acetazolamide in solution. Because of the bitter taste of acetazolamide, sweetening agents (simple syrup, sorbitol solution, and artificial sweeteners) and flavors (raspberry, sweet, and menthol) were added to the final formulations. A buffer (either phosphate or citrate) solution was used to maintain a pH value of 4 (pH of maximum stability as reported earlier) to minimize hydrolysis. The final dosage forms were stable for at least 90 days at 37 degrees C (loss of potency of 5%). According to FDA guidelines, a tentative expiry date of 2 years at 25 degrees C is justifiable. PMID- 2273471 TI - Polarographic study of nifurtimox. AB - Nifurtimox is polarographically reducible over the whole pH range, the nitro group being reduced to the hydroxylamine group in a 4e process and subsequently the amine being formed in a 2e process at a pH value below 4. The C = N-N linkage is reduced by a mechanism involving reductive fission of the N-N bond. The differential pulse polarographic peaks for the reduction of the nitro group to the hydroxylamine group at pH 6 were used in developing a new polarographic method for the determination of nifurtimox in pharmaceutical forms. PMID- 2273472 TI - Isolation, synthesis, and evaluation of a series of indencarbazates as hypotensive agents. AB - Two indencarbazates, 1 and 2, were isolated from the sponge Cliona caribboea. These compounds were found to possess mild hypotensive activity. A series of analogues of 1 was synthesized in order to study the structure-activity relationship of this unique class of compounds. A variety of structural changes did not result in a consistent pattern of biological activity. PMID- 2273474 TI - The LP/VN as advocate for the homeless. PMID- 2273473 TI - Glass-rubber transitions of cellulosic polymers by dynamic mechanical analysis. AB - The glass-rubber transition temperatures (Tg) of several cellulosic polymers [hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC)] have been examined using dynamic mechanical analysis (DMA). The melting temperatures of the above polymers were examined using a hot stage melting point apparatus. The primary Tg of three different grades of HPMC (3, 6, and 15 cps) were determined to be 160, 170, and 175 degrees C, respectively. The primary Tg of the HEC film was determined as 120 degrees C. The HPC film did not indicate a primary Tg. These cellulosic polymers also displayed secondary transitions. Hot stage melting of HPMC and HPC was observed at 225 to 254 degrees C and 190 to 195 degrees C, respectively. The HEC powder did not exhibit a melting temperature, but became darker at temperatures greater than 150 degrees C. PMID- 2273475 TI - The LPN's responsibilities in drug therapy. PMID- 2273476 TI - Your CE topic (no. 51). Drug therapy in patients with ostomies. PMID- 2273477 TI - Health care for migrant workers: the shame of it. PMID- 2273478 TI - The homeless. PMID- 2273479 TI - Radiation safety and the nurse. PMID- 2273480 TI - The needs of the homeless. PMID- 2273481 TI - Caring for ourselves. PMID- 2273482 TI - Tryptophan--new questions for an old amino acid. PMID- 2273483 TI - Eosinophilia-myalgia syndrome--old questions for a new syndrome. PMID- 2273484 TI - A study of fatigue in systemic lupus erythematosus. AB - Fifty-nine patients with systemic lupus erythematosus were evaluated by questionnaires, histories, physical examinations and routine laboratory studies in order to better understand their fatigue. The fatigue severity scale (scored from 1 to 7) was used to measure fatigue and yielded a mean score +/- SD of 4.6 +/- 1.5. Fifty-three percent of the patients reported that fatigue was their most disabling symptom. Although perceived as severe, the symptom of fatigue did not correlate significantly with any of the laboratory measures. However, there was a significant correlation between fatigue and the physician's rating of disease activity. Fatigue also correlated significantly with depression which accounted for 21% of the variation in fatigue scores. PMID- 2273485 TI - Vasculitis as a paraneoplastic syndrome. Report of 11 cases and review of the literature. AB - In a study of 222 patients with vasculitis, we identified 11 who had an associated neoplasia. Seven had hematological neoplasia and 4 had solid malignant tumors. In 4 patients vasculitis gave the first evidence of the neoplasia or of its recurrence. Nine of our patients had cutaneous vasculitis. The other 2 had vasculitis involving the intestine and resulted in acute abdomens. These 2 patients needed prednisone treatment for the vasculitis. Neoplasia should be considered in patients with vasculitis without an apparent cause. PMID- 2273486 TI - Epidermal growth factor receptor of fibroblasts from patients with scleroderma. AB - Epidermal growth factor receptor (EGF-R) of fibroblasts from 3 patients with scleroderma (progressive systemic sclerosis, PSS) was studied by radioiodinated EGF binding assay. The binding was 60.9 +/- 4.0% of normal fibroblasts, and the Scatchard plots showed a decrease in the affinity for EGF, not in the number of EGF-R. PSS fibroblasts expressed higher levels (1.15-2.45-fold) of RNA for the v erbB (EGF-R gene). All-transretinoic acid (retinoid) had little effect on EGF-R, v-erbB gene expression and the proliferation of PSS fibroblasts. These data concerning the abnormality in the EGF-R may all constitute a feature of PSS fibroblasts. PMID- 2273487 TI - Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis. AB - In order to assess the interaction between methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAID), we studied the pharmacokinetics of oral MTX alone and in the presence of the usually prescribed NSAID in 7 children with chronic arthritis. The NSAID studied included tolmetin, indomethacin, naproxen, and aspirin. Six patients were treated with multiple NSAID. The mean MTX elimination half-life was prolonged when NSAID were coadministered (1.7 +/- 0.5 vs 1.2 +/- 0.1 h; p = 0.03). However, neither the apparent MTX clearance (CI) (10.6 +/- 5.5 vs 13.1 +/- 3.5 l/h; p = 0.19), the area under the serum MTX concentration-time curve (Auc) (2.1 +/- 1.0 vs 1.5 +/- 0.6 mumol/l/h; p = 0.08) or the apparent volume of distribution (Vd) (23.0 +/- 6.2 vs 21.9 +/- 6.4 l; p = 0.53) was significantly altered by the administration of NSAID. Although the differences between the mean Cl and Auc were not statistically significant, a wide variation in the impact of NSAID on MTX Cl was observed. In 6 of 7 patients, the Auc increased during NSAID administration from 19 to 140%. This degree of increase may be clinically significant in some individuals. It is consequently recommended to closely monitor patients who are receiving MTX and NSAID for MTX toxicity until these results can be verified in a larger population. PMID- 2273488 TI - Some osseous and soft tissue causes of human intervertebral canal (foramen) stenosis. AB - Much attention has been paid to the causes of vertebral canal stenosis in humans but relatively little has been documented with regard to intervertebral canal (intervertebral "foramen," lateral spinal canal, nerve root canal) stenosis. As the dural sleeve ends at the outer opening of the intervertebral canal, a false "normal" myelogram is possible when a space occupying lesion occurs beyond the subarachnoid space. Also, if stenosis affects only vascular structures, compression of these structures cannot be noted during myelography, so venous stasis may be overlooked. Our cadaveric study investigates some causes of intervertebral canal stenosis due to encroachment by bony and soft tissue structures, and low magnification photomicrographs are used to illustrate some causes of stenosis. PMID- 2273489 TI - HLA class II and T cell receptor gene polymorphisms in psoriatic arthritis and psoriasis. AB - HLA-DRB, DQA and DQB genes as well as the T cell receptor (TcR) alpha, beta, and gamma genes were studied by Southern blot analysis of genomic DNA from patients with psoriatic arthritis (PsA) and psoriasis alone (Ps). A subtype of DR7, DR7a, was found in 38.8% of patients with PsA, 41.5% of patients with Ps, and in 8% of healthy individuals (N) (PsA vs N: pc = 0.0002, RR = 7.1; Ps vs N: pc = 0.0002, RR = 7.9). No association with TcR genes was found. Our findings suggest either that the DR7a allele may be in linkage disequilibrium with HLA-Cw6 or that it may be an important susceptibility factor for PsA and Ps. PMID- 2273490 TI - A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome. AB - Noninvasive tests for carpal tunnel syndrome (CTS) are of limited diagnostic value. A self-administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of CTS. Diagrams are rated classic CTS, probable, possible or unlikely. Diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints. A hand diagram rating of classic or probable CTS had sensitivity of 0.64, specificity of 0.73 and positive predictive value of 0.58. The negative predictive value of an unlikely diagram was 0.91. We conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening. PMID- 2273491 TI - A possible role for antiphospholipid antibodies in acquired cardiac valve deformity. AB - We studied the frequency of antiphospholipid antibodies (aPL) in patients undergoing cardiac valve replacement, and present the results in the context of the pathology of the valve lesions. Forty-eight consecutive patients undergoing valve replacement were studied. Of the whole group, 15 (31%) had antibody levels greater than 2 SD above the mean for a control group of healthy persons and 11 (23%) had a level of greater than 3 SD. There was an increased frequency of elevated antibody levels in patients with valves showing fibrocalcific change and a significant association between aPL and valve thrombus. The possible role of these antibodies in the pathogenesis of the valve lesions is discussed. PMID- 2273492 TI - Differential diagnosis between osteitis condensans ilii and sacroiliitis. AB - Sacroiliitis of seronegative spondyloarthropathy may sometimes show on pelvis plain films findings indistinguishable from those of osteitis condensans ilii. Computed tomography (CT) can differentiate earlier than plain radiography between the 2 conditions; furthermore, it should also be possible to make this differentiation clinically. The aim of our study was to verify whether the criteria recently proposed by the European Spondylarthropathy Study Group (EESG) for the classification of spondyloarthropathy are useful. CT scans through the synovial part of the sacroiliac joints of 7 consecutive patients meeting the ESSG criteria and showing typical findings of osteitis condensans ilii on plain films were mixed with those of 15 consecutive patients with osteitis condensans ilii not meeting the ESSG criteria. Scans were examined for joint space and surface abnormalities blindly and independently by 2 observers. Six patients in the spondyloarthropathy group and one in the osteiitis condensans ilii group showed clear erosions and/or joint space narrowing of less than 2 mm in at least one joint. The difference was statistically significant (p less than 0.001). Our results suggest that by using criteria valid for the whole group of seronegative spondyloarthropathies, it is possible to differentiate clinically between seronegative spondyloarthropathies with sacroiliitis mimicking osteitis condensans ilii and "true" osteitis condensans ilii. PMID- 2273493 TI - Effects of prostaglandin E1 on collagen diseases with high levels of circulating immune complexes. AB - Prostaglandin E1 (PGE1) was administered to 4 patients with collagen diseases presenting with high levels of circulating immune complexes (CIC) in sera. Our study patients had progressive systemic sclerosis, systemic lupus erythematosus, polyarteritis nodosa, and rheumatoid arthritis. In all 4 patients, CIC levels significantly decreased after administration of PGE1 by continuous infusion at 10/ng/kg/min via central venous catheter for 72 h. In addition, the skin ulcer in a patient with PSS healed completely, and the finger necrosis in a patient with RA improved. These results suggest that PGE1 given by continuous venous infusion is effective in reducing CIC, in addition to improving peripheral vascular disorders. PMID- 2273494 TI - Ankylosing spondylitis with exuberant sclerosis in the sacroiliac joints, symphysis pubis and spine. AB - We report the case of a man with ankylosing spondylitis involving the symphysis pubis and some intervertebral discs in addition to the sacroiliac joints. The bone adjacent to each inflammatory area showed an unusually exuberant sclerosis. In the early phases of evolution the appearance of sacroilitis was indistinguishable from that of osteitis condensans ilii. PMID- 2273495 TI - Miller Fisher syndrome in systemic lupus erythematosus. AB - We describe the first case of Miller Fisher syndrome, a Guillain Barre variant, complicating systemic lupus erythematosus. The symptoms and signs mimicked a brainstem syndrome. Despite treatment with high dose gamma globulin, our patient worsened and required mechanical ventilation. After plasma exchange, the patient improved. PMID- 2273496 TI - Mixed connective tissue disease with arterial thrombosis, antiphospholipid antibodies and heparin induced thrombocytopenia. AB - We report a patient with mixed connective tissue disease (MCTD) who presented with thrombosis of the right femoral artery in association with antiphospholipid antibodies (aPL). When treated surgically and with heparin prophylaxis, she developed heparin induced thrombocytopenia and thrombosis which necessitated amputation of a lower limb. Thus our patient developed 2 separate groups of autoantibodies associated with thrombotic events. Our case highlights an association between thrombosis, aPL and MCTD. Furthermore, it emphasizes a need for intensive monitoring when hypercoaguable individuals with connective tissue disorders are treated with heparin. PMID- 2273497 TI - Relapsing polychondritis in pregnancy. AB - A 25-year-old patient presented at 14 weeks of her 3rd pregnancy with chondritis affecting the cartilaginous portion of her right ear. The clinical syndrome of recurrent chondritis, scleritis, iritis and arthritis supported a diagnosis of relapsing polychondritis. Fetal and maternal outcomes were favorable despite steroid dependent active disease during the period of fetal organogenesis. Chondritis was limited to the 3rd pregnancy, ocular inflammation occurring in the 2nd and 3rd pregnancies. A 4th pregnancy was uneventful. This may represent the first case of relapsing polychondritis in pregnancy. PMID- 2273498 TI - L-tryptophan induced eosinophilia-myalgia syndrome. AB - We describe the spectrum of clinical and histologic abnormalities of 11 women with L-tryptophan induced eosinophilia-myalgia syndrome. The illness is characterized by musculoskeletal symptoms including myalgias, arthralgias and paresthesias. The physical findings consist of muscle tenderness, neuropathies, rash, peripheral and periorbital edema. Electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3. Skin and muscle biopsies showed fascial edema, inflammation and perivascular infiltrates in the skin, whereas perineural infiltrates and venulitis were identified in muscle. Seven patients were treated with prednisone; eosinophilia disappeared promptly although myalgias and neuropathy persisted. PMID- 2273499 TI - Eosinophilia-myalgia syndrome associated with L-tryptophan use. AB - The eosinophilia-myalgia syndrome associated with the use of oral preparations of the amino acid L-tryptophan was recognized in late 1989. We describe the clinical and laboratory manifestations, pathological findings and early clinical course of 20 patients with the eosinophilia-myalgia syndrome. Prominent clinical findings included severe myalgias limiting function, fatigue, rashes, edema and weight gain, weight loss, muscle weakness and shortness of breath. Laboratory findings included eosinophilia (often marked), normal erythrocyte sedimentation rate, and elevated aldolase with normal or low creatine kinase values. On biopsy fascial inflammation was always seen consisting of lymphocytes, histiocytes and eosinophils in a perivascular distribution. Invasion of the vascular wall by lymphocytes was seen in 20%. Capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25% of cases. Two patients improved with no therapy. Ten patients responded to therapy with prednisone alone. Three patients have had progressive disease and one of these died. The relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed. PMID- 2273500 TI - Microangiopathy in the eosinophilia-myalgia syndrome. AB - The eosinophilia-myalgia syndrome associated with the ingestion of L-tryptophan was recognized in late 1989. We describe our pathologic study of skin, fascial, and muscle biopsies from 21 patients evaluated by light microscopy, histochemistry, and electron microscopy. A perivascular, lymphocytic infiltrate with eosinophils was present in the dermis, fascia, and skeletal muscle. Lymphocytic infiltration of arteries and arterioles was seen. Ultrastructurally, capillary and arteriolar endothelial cell thickening and necrosis was present. This microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome. PMID- 2273501 TI - An eosinophilia-myalgia syndrome associated with an L-tryptophan containing product. AB - A syndrome of eosinophilia and myalgias associated with the usage of L-tryptophan containing products has been recently described by the Centers for Disease Control. We report a case of this new clinical entity, highlighted by severe myositis, and compare this illness with similar reported syndromes. PMID- 2273502 TI - Eosinophilic myositis an expression of L-tryptophan toxicity? AB - Eosinophilia-myalgia syndrome possibly due to L-tryptophan is a new clinical entity that has been recently reported. We describe the clinical presentation of eosinophilia, eosinophilic pustular folliculitis, myalgia, and eosinophilic myositis, that led to respiratory failure in a young man taking an L-tryptophan containing compound. PMID- 2273503 TI - Eosinophilia-myalgia syndrome in association with L-tryptophan ingestion. AB - The association between the recently described eosinophilia-myalgia syndrome and L-tryptophan is now well established. We describe a patient with eosinophilia myalgia syndrome who developed incapacitating myalgias and peripheral eosinophilia responsive only to high dose corticosteroids. When massive upper gastrointestinal hemorrhage developed while receiving corticosteroid therapy, surgery was complicated by striking abdominal wall rigidness. A discussion of this case and of eosinophilia-myalgia syndrome is presented. PMID- 2273505 TI - Linkage studies in sulfoxidation status, HLA and rheumatoid arthritis. PMID- 2273504 TI - L-tryptophan associated eosinophilia-myalgia syndrome. AB - Environmental chemicals are increasingly incriminated in the pathogenesis of several disease states. The eosinophilia-myalgia syndrome is a recently described entity attributed to the ingestion of the normal dietary amino acid L-tryptophan. We describe a patient who fulfills criteria for the eosinophilia-myalgia syndrome and who was ingesting supplemental L-tryptophan. Exhaustive investigations failed to reveal other causes for her eosinophilia or her myalgic/neuropathic complaints, and she improved dramatically when she discontinued the L-tryptophan supplements. The mechanisms whereby this chemical may induce this syndrome are discussed. PMID- 2273506 TI - SF eosinophilia in an adult with acute rheumatic fever. PMID- 2273507 TI - Intraarticular progestins in rheumatic diseases. PMID- 2273508 TI - SLE, thrombocytopenia, and HTLV-I. PMID- 2273509 TI - Iliopsoas bursitis. PMID- 2273510 TI - Arthritis and food allergy. PMID- 2273511 TI - Prolactin levels in men with SLE and RA. PMID- 2273512 TI - Fulminant soft tissue infection by Salmonella enteritidis in SLE. PMID- 2273513 TI - Tendon rupture in SLE. PMID- 2273514 TI - Recurrence of adult Still's after pregnancy. PMID- 2273515 TI - Longterm survival after renal crisis. PMID- 2273516 TI - Anticardiolipin antibodies in infectious mononucleosis. PMID- 2273517 TI - How we got to be where we are. PMID- 2273518 TI - Safety issues related to DMARD therapy. AB - The old pyramidal approach to treatment of rheumatoid arthritis depended most fundamentally upon the beliefs that the most effective agents were also the most toxic, that toxic-therapeutic ratios of different drug categories were about the same, and that one should first use the least effective and least toxic drugs. Recent data, however, demonstrate the often severe toxicity of the nonsteroidal antiinflammatory drugs and the surprisingly good safety record of certain disease modifying antirheumatic drugs. New analyses tend, in general, to support less aggressive monitoring strategies. Some of the fundamental assumptions of the old pyramidal strategy are shown to have been inaccurate. PMID- 2273519 TI - Azathioprine and methotrexate as combination chemotherapy in rheumatoid arthritis. AB - Azathioprine or methotrexate (MTX) are each established, and comparably effective, therapies for rheumatoid arthritis (RA). An ongoing, still double blind, 3-arm, 24-week study comparing azathioprine or MTX, or azathioprine and MTX in RA is described. With 146 (of 210 total) patients enrolled, it is apparent that all 3 treatment groups demonstrate clinically significant improvement at Week 24. One treatment arm (Group 1) showed a greater degree of improvement in raw mean scores for most outcome variables. Another treatment arm (Group 2) had an adverse effect dropout rate exceeding the sum of adverse effect dropouts from Group 1 and Group 2. Most adverse effects were due to gastrointestinal intolerance. PMID- 2273520 TI - The systematic study of drug therapy in rheumatoid arthritis. AB - Important advances in therapeutics for rheumatoid arthritis (RA) will probably require coordination of the experience with new developing agents with an ongoing program of systematically collected open data, and formal controlled clinical trials to address key problematic issues. Controlled trials, despite formidable obstacles, not the least of which is the lack of satisfactory end points, are necessary because randomized treatment assignment is the only valid way to obtain results with a defined degree of certainty. A formal test of whether early aggressive intervention can arrest disease appears feasible. On the other hand, it does not now seem desirable to pursue a controlled, blinded study of RA over the longterm. PMID- 2273521 TI - Challenging the therapeutic pyramid: a new look at treatment strategies for rheumatoid arthritis. AB - Traditional therapy of rheumatoid arthritis (RA) has been dominated by the therapeutic pyramid. This approach is not working. The designation of drugs as either antiinflammatory or disease modifying is not borne out by experience. We possess a number of drugs, each only partially effective against inflammation, that work by poorly understood mechanisms. Until a major breakthrough appears, it is proposed to treat RA with a combination of these medications early in the disease course, to gain control of the inflammation, and then bridge to a simplified program by withdrawing drugs sequentially. PMID- 2273522 TI - The beat-to-beat blood pressure response to postural change in young and elderly healthy adult males. AB - Heart rate and blood pressure were studied with the beat-to-beat tracking cuff system in two groups (n = 20 per group) of healthy, unmedicated males, one between 60 and 75 years of age and the second between 18 and 29 years of age. The study confirms the previously reported blunted heart rate response to standing and the fact that, when blood pressure is recorded by conventional means, the response exhibited during orthostasis does not differ in healthy groups of young and elderly subjects. With the tracking cuff system, however, the elderly exhibited a smaller immediate systolic and diastolic drop in response to the change to upright posture and less variability in beat-to-beat blood pressure changes. The results have implications for cardiovascular studies, where age and posture can influence both blood pressure and heart rate. PMID- 2273523 TI - Selection, training, and quality control of Type A interviewers in a prospective study of young adults. AB - This paper describes Type A/B interviewer selection, training, and quality control results in a prospective study of coronary artery risk development in young adults (CARDIA). Interviewer behaviors from 152 CARDIA structured interviews were audited and compared with 747 Western Collaborative Group Study (WCGS) interviews and 577 Multiple Risk Factor Intervention Trial (MRFIT) interviews. The results show success in modeling the CARDIA interviewer behaviors on those of the WCGS. CARDIA interviews were very similar to WCGS interviews for interview length, number of questions asked, and speed of speaking; they were similar to MRFIT interviews in latency of asking questions. CARDIA interviewer behaviors remained fairly consistent over the four time periods. Comparing the clinics, there were regional differences in latency of asking and speed of speaking, with the Southern clinic having a longer asking latency and speaking more slowly. There were differences between individual interviewers in most characteristics, particularly those that were more free to vary. The study provides procedures and guidelines designed to maintain quality control of the structured interview process. PMID- 2273524 TI - Cephalic blood flow correlates of induced headaches. AB - The purpose of this study was to examine the cephalic blood flow patterns of subjects with frequent headaches during a headache induction procedure. Thirty six subjects with muscle-contraction, migraine, or mixed headache symptoms were exposed to a 1-hr stressor designed to induce a headache while multiple cephalic blood volume pulse amplitude (BVPA) was measured. Thirty subjects reported a headache during the procedure, and the procedure was associated with significant changes in several cephalic BVPA measures. Between-group differences were found for several cephalic BVPA sites and there were significant correlations between induced headache activity and cephalic BVPA measures for most subjects. The results support causal roles for psychosocial stressors and cephalic blood flow in muscle-contraction and migraine headache. PMID- 2273525 TI - Internal structure of prevention and dental health behaviors. AB - Previous work investigating the internal structure of preventive health behavior (PHB) has not included a representative sample of dental health behaviors. Consequently, it has not been possible to evaluate whether dental dimensions of health behavior exist or whether dental behaviors are part of other health behavior dimensions. The results of a principal-components analysis of PHBs in which a larger sample of dental health behaviors is included shows that purely dental dimensions of health behavior emerge in a sample of 350 university students and faculty. Dental health behavior may need to be conceptualized as a dimension of health behavior separate from other PHBs. PMID- 2273526 TI - Assessing skills for refusing cigarettes and smokeless tobacco. AB - Hops and colleagues developed an audiotaped refusals skills test in which students respond to cigarette offers and their responses are scored for content. The present study employed a modified analogue skills test. Modifications included adding a separate subscale for smokeless tobacco, emphasizing repeated offers and group pressure, and rating the quality of responses (good, fair, poor). The test was evaluated in four seventh-grade classrooms (N = 78). Half had participated in a refusals skills training program; the others were controls. Intervention subjects provided more "good" responses and fewer "poor" responses than controls. In a multiple regression, repeated and group offers were associated with the quality of response, while offerer's gender and type of tobacco variables were not associated. In a second regression, experimental condition was associated with quality of the responses, while gender, ethnicity, exposure to tobacco, use of tobacco, and attitudes toward the test were not associated. PMID- 2273528 TI - Hormonal regulation of protein metabolism. PMID- 2273527 TI - Cardiovascular responses to a quantified dose of nicotine as a function of personality and nicotine tolerance. AB - Correlations between cardiovascular effects of a quantified dose of nicotine and personality measures previously shown to predict coronary heart disease were obtained. Thirty male smokers smoked a popular brand of a regular strength cigarette (1.0 mg FTC-estimated nicotine delivery) on one occasion and a nicotine free cigarette on another occasion by means of a quantified smoke delivery system. Partial correlations controlling for effects of body weight, questionnaire-assessed nicotine tolerance, and cardiovascular responses to the nicotine-free control cigarette showed Jenkins Activity Survey Type A scores to correlate positively with nicotine-induced increase in diastolic blood pressure but negatively with nicotine-induced increase in systolic blood pressure. Partial correlations indicated that trait anxiety and depression were significantly associated with nicotine-induced heart rate increases but not with nicotine induced blood pressure responses. PMID- 2273529 TI - Energy balance in elderly patients after surgery for a femoral neck fracture. AB - To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery. REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02). REE was positively correlated with body weight (r = 0.69, p less than 0.005). Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day. Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05). Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero). When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero). Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273530 TI - Role of the lungs in maintaining amino acid homeostasis. AB - The relative contributions of skeletal muscle and the pulmonary bed in maintaining amino acid homeostasis were studied. Inasmuch as more than 60% of whole blood amino acid nitrogen is transported as glutamine and alanine, the flux of these two amino acids across the lungs (n = 20) and hindquarter (n = 20) was determined in the postabsorptive adult rat. Both skeletal muscle and the lungs released net amounts of glutamine and alanine in the postabsorptive state. Blood flow to the hindquarter was approximately 16% of cardiac output (3.8 +/- 0.3 cc/100 g BW/min), while pulmonary blood flow (cardiac output) was 23.7 +/- 1.7 cc/100 g BW/min. Thus, despite a lower glutamine concentration difference across the lungs (-32 +/- 6 mumol/liter) compared with the hindquarter (-59 +/- 10 mumol/liter (p less than 0.01), the lungs released significantly more glutamine (741 +/- 142 nmol/100 g BW/min) than the hindquarter (208 +/- 39 nmol/100 g BW/min) (p less than 0.01) because of the significantly higher pulmonary blood flow. Similarly, the concentration difference for alanine across the lungs was less than that of the hindquarter (-24 +/- 8 mumol/liter vs -60 +/- 12 mumol/liter, p less than 0.01) but the lungs released significantly more alanine than the hindquarter (553 +/- 159 nmol/100 g BW/min vs 221 +/- 41 nmol/100 g BW, p less than 0.01. Compositional studies demonstrated that the hindquarter comprises 40% of total body muscle mass in the rat; thus both total skeletal muscle mass and the lungs contribute approximately equally to the maintenance of blood glutamine and alanine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273531 TI - Use of human growth hormone combined with nutritional support in a critical care unit. AB - The administration of growth factors may potentially accelerate recovery during critical illness by reducing body protein catabolism, enhancing wound healing, and improving skeletal muscle function. The purpose of this phase 1 study was to evaluate the safety and initial efficacy of a recombinant growth factor, human growth hormone (GH), combined with nutritional support in a critical care unit. Following an initial control week, 11 individuals received GH (10 mg/day) daily for 1-6 consecutive weeks. Near constant nutrient intake was provided via parenteral and/or enteral feedings throughout the study period. Vital signs and other clinical parameters, blood values, and nutrient excretion were monitored daily. GH administration was not associated with clinically significant adverse effects. During the first 2 weeks of study, nitrogen excretion decreased from 1356 +/- 157 mmol/day (19.0 +/- 2.2 g/day) during control to 899 +/- 107 mmol/day (12.6 +/- 1.4 g/day) with growth hormone (p less than 0.002) in association with markedly reduced urea generation. Significant reductions in potassium excretion (control 100 +/- 11 mmol/day vs 69 +/- 6 with GH; p less than 0.01) and phosphorus excretion (31 +/- 5 mmol/day vs 18 +/- 3; p less than 0.025) also occurred during GH. The protein-conserving effects of GH were sustained during several weeks of treatment. Growth hormone enhanced the efficiency of administered protein and facilitated nitrogen retention without clinically significant adverse effects in this small patient group. Controlled trials are indicated to determine whether use of this anabolic hormone reduces hospitalization time and improves other clinical outcomes in severely injured patients when combined with appropriate nutritional support. PMID- 2273532 TI - Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci. AB - Using a quantitative in vitro model simulating clinical conditions, we studied the efficacy of conventional and nonconventional 3-day therapies involving vancomycin for treating the internal surface of catheters colonized with a slime producing strain of Staphylococcus epidermidis. When infused for 1 hr every 8 hr through the catheter at the daily dose recommended for a 10-kg child (450 mg), vancomycin alone reduced bacterial colonization but failed to sterilize the inserts. Vancomycin was more active in combination with netilmicin (25 mg for 1 hr every 8 hr), rifampin (150 mg for 90 min every 12 hr), or fosfomycin (500 mg for 4 hr every 6 hr), but the catheters were inconsistently decontaminated after 3 days of treatment. Two nonconventional modes of antibiotic administration were tested for their capacity to ensure high levels of vancomycin in the catheter lumen over a prolonged time. Vancomycin infused continuously through the catheter at a daily dose of 450 mg had the same poor sterilizing effect as vancomycin administered intermittently. On the contrary, catheters were totally decontaminated when 2.5 mg of vancomycin in a volume of 0.5 ml were injected twice daily into noninfused catheters, confirming that the antibiotic-lock technique is an approach of great interest to sterilize the internal surface of catheters colonized with staphylococci. PMID- 2273533 TI - Dietary intake in patients with acquired immunodeficiency syndrome (AIDS), patients with AIDS-related complex, and serologically positive human immunodeficiency virus patients: correlations with nutritional status. AB - One of the major clinical manifestations of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) is the development of cachexia. This most likely results from a multifactorial interplay of poor diet, malabsorption, and altered metabolism. To assess the potential role of nutrient intake in the development or persistence of malnutrition, a detailed analysis was performed of a 72-hr diet record in clinically stable patients with AIDS (N = 18), ARC (N = 12) and in human immunodeficiency virus (HIV) seropositive controls without significant manifestations of disease (N = 13). Total calorie intake was 39.1 +/- 13.2 kcal/kg/day in AIDS patients vs 34.6 +/- 7.8 kcal/kg/day in ARC patients or 31.9 +/- 17.7 kcal/kg/day in HIV seropositive cases (all p = NS). Likewise, mean protein intakes were similar among the groups and exceeded recommended daily dietary allowance (RDA) guidelines. The mean body weight changes from the inception of illness were -11 +/- 1% in AIDS, -6 +/- 7% in ARC, vs +3 +/- 2% in HIV-seropositive-only cases (p less than 0.05 vs AIDS and ARC). Dietary vitamin and mineral analysis revealed that 88% of AIDS, 88% of HIV seropositive, and 89% of ARC patients were ingesting less than 50% RDA for at least one nutrient. The mean number of deficiencies per patient was 1.8 +/- 1.3 in AIDS, 3.8 +/- 3.5 in ARC, and 2.9 +/- 2.5 in HIV-seropositive-only cases (p less than 0.05 AIDS vs ARC). There were no significant correlations between specific anthropometric measurements and dietary intakes of protein or fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273534 TI - Cori cycle contribution to plasma glucose appearance in man. AB - The contribution of recycled glucose to gluconeogenesis and plasma glucose appearance (Cori cycle) has previously been calculated from liver balance studies and from infusions of labeled glucose. Both techniques resulted in the estimate that Cori cycle activity accounts for about 15% of plasma glucose appearance. However, it is now understood that the specific activity of gluconeogenic precursors, which is used to determine their contribution to glucose appearance in plasma, overestimates the true precursor specific activity. Using earlier published data on substrate utilization and glucose turnover kinetics in humans, an empiric correction factor of 2.7 is derived which may approximately account for label dilution in the precursor pool. Use of this factor confirms that the former estimate of the contribution of Cori cycle activity to glucose turnover should be revised substantially upwards. PMID- 2273536 TI - Intestinal obstruction by distension of a Foley jejunostomy catheter. AB - Jejunostomies can be effective in permitting postoperative nutritional support, particularly in the patient with complicated gastrointestinal disease. In the case presented, however, distension of the Foley balloon catheter, used as the jejunostomy tube, led to intestinal obstruction which was not initially detected. Following radiographic identification of the problem, removal of the air from the Foley balloon allowed the patient to complete his convalescence from surgery. The possibility of obstruction from the Foley jejunostomy catheter should be recognized as a potential problem in the postoperative period. PMID- 2273535 TI - Factors contributing to increased energy expenditure in thermal injury: a review of studies employing indirect calorimetry. AB - In summary, a remarkably close agreement exists for the mean MEE measured in 28 studies of severe burn trauma. This is especially surprising given the variability in sample sizes, measurement techniques, study designs, and DPBs studied. The mean MEE calculated from the data published in these reports is listed in the final column of Table I. For more than 450 cases, an unweighted MEE is 2750 +/- 85 kcal/day. For those studies prior to 1980, the mean MEE exceeds 3000 kcal/day in eight of 14 reports vs only two of 14 published after 1980. Even so, the mean MEE for the pre-1980 reports differs by only 200 kcal/day (2960 +/- 120, n = 14). The accepted notion that the degree of elevation in MEE is in proportion to the % BSAB up to about 60% BSAB is useful in a general sense but must be applied with caution. The recent studies, which include proportionately more burns exceeding 80% BSAB, suggest an elevation in MEE in these cases. Nevertheless, a physiologic plateau apparently exists at or slightly below 2 x normal RMR at the peak of MEE. The magnitude of the MEE response results from an undefined interaction among several factors of which some have been examined while others such as inflammatory mediators are only beginning to receive study. The contributions to reduction in MEE from interventions to control cardiac output and peripheral cooling, core temperature, evaporative water (heat) loss, and substrate cycling have been reviewed. The importance of indirect calorimetry in patient care is highlighted by the large variability in similarly injured individuals and in the unexplained component of regression analyses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273537 TI - Central venous access in infants and small children: a new technique. PMID- 2273538 TI - Measurement of elemental nitrogen by chemiluminescence. PMID- 2273539 TI - [Teaching cardiopulmonary resuscitation to medical students]. PMID- 2273540 TI - [The changes in total body water in patients with prolonged anesthesia and surgery]. AB - We studied the influence of prolonged anesthesia and surgery on total body water (TBW) with tetrapolar bioelectrical impedance analysis (BIA). Eight patients who underwent prolonged anesthesia were selected as the subjects of the study and were compared with nine patients who underwent surgery of less than 3 hours. Plasma hormone concentrations were also examined. In the prolonged anesthesia patients, TBW increased significantly as compared with those of the patients who underwent short surgery (P less than 0.05). TBW showed the most remarkable increase on the first post operative day. Plasma ADH and aldosterone concentrations increased in the patients of both groups. However, we could not find a significant relationship between TBW and plasma hormone concentrations. BIA seems to be a useful method to estimate TBW during perioperative periods. However, further detailed investigation would be necessary to obtain a reliable technique in such an unstable condition. PMID- 2273541 TI - [Transfusion for operation: reduction and proper preparation of blood for transfusion]. AB - In order to minimize preoperative transfusion requirements and to order proper preoperative transfusion blood, we induced deliberate hypotension and analyzed preoperative preparation of blood with C/T (cross-match/transfusion) ratio. We tried to establish a maximum surgical blood order schedule (MSBOS) based on the surgical transfusion experience of about 10 operations at our hospital. Deliberate hypotension was induced with prostaglandin E1 (PGE1) in 14 patients with mastectomy. Bleeding volume in PGE1 group (n = 7) was reduced to approximately 50% of control group (n = 7) at average dose of 35 +/- 25 ng.kg 1.min-1 with enough urine output. The dose of PGE1 was smaller than other reports because of the application of continuous epidural block to general anesthesia in all cases. Average C/T ratio was 4.6 and it was 3.6-24 in the 10 operations, which are higher than recommended value of the Ministry of Health and Welfare as well as ASA committee. We confirmed deliberate hypotension with PGE1 and continuous epidural block under general anesthesia were useful to minimize blood loss during mastectomy and clarified the improvement of the present preoperative blood ordering. PMID- 2273542 TI - [Prediction of the need for postoperative mechanical ventilation in myasthenia gravis patients]. AB - The prediction of the need for postoperative mechanical ventilation in 23 myasthenia gravis patients, who had undergone thymectomy from January 1983 to December 1989, was evaluated. Five patients who had needed postoperative mechanical ventilation over 24 hours were compared with the patients in whom the tracheal tubes had been uneventfully extubated within 24 hours postoperatively. In this study, 47.8%, 78.3%, 91.3% of the patients were correctly predicted using the scoring systems proposed by Leventhal et al., Makii et al. and Kimura et al., respectively. The product of %VC by FEV1.0% was proposed in this study for the prediction of the need of postoperative mechanical ventilation in patients with myasthenia gravis. If the product is less than 8,300, the patient is expected to need postoperative mechanical ventilation. Nineteen patients out of 23 cases (82.6%) were predicted correctly by this value. Only one patient, who had been predicted to be in no need, was actually ventilated for 3 days. In conclusion, the product of %VC by FEV1.0% is a simple and practical method of predicting whether a patient with myasthenia gravis undergoing thymectomy requires postoperative mechanical ventilation or not. PMID- 2273543 TI - [Effects of lumbar or thoracic epidural anesthesia on median nerve somatosensory evoked potentials]. AB - Somatosensory evoked potentials (SSEP) are used increasingly to monitor the integrity of neural pathways in anesthetized patients. To evaluate the influence of epidural anesthesia on the central nervous system, we studied the effects of lumbar or thoracic epidural anesthesia with lidocaine on the median nerve SSEP in 9 patients. The peak latencies (N1, P2, N2) and amplitudes (N1-P2, P2-N2) of the SSEP response over the sensory cortex were recorded before and 15 min after epidural anesthesia. The peak latencies of control and post epidural anesthesia of N1, P1, N2 were 19.2 +/- 1.7 msec, 19.6 +/- 1.6 msec (N1), 24.7 +/- 2.3 msec, 25.7 +/- 2.0 msec (P2), 32.8 +/- 2.8 msec and 34.6 +/- 2.5 msec (N2), respectively. The amplitude of control and post epidural anesthesia of N1-P2, P2 N2 were 4.5 +/- 2.9 microV, 5.9 +/- 6.6 microV (N1-P2), 4.4 +/- 3.2 microV and 5.6 +/- 5.2 microV (P2-N2), respectively. Peak latencies of all components (L1, P2, N2) increased after epidural anesthesia compared with control values. Amplitude of N1-P2 increased significantly following epidural anesthesia compared with control values. The data obtained in this study were contrary to the previous concept that anesthetic agents generally increase the latency of SSEP and decrease their amplitude. PMID- 2273544 TI - [Relationship between three phase bone scintigram and prognosis after sympathetic blockade in reflex sympathetic dystrophy of the hand]. AB - We attempted to correlate the changes in three phase bone scintigram (TPBS) with prognosis after sympathetic blockade in reflex sympathetic dystrophy (RSD) of the hand. Subjects were 12 patients of RSD in acute or dystrophic stage, who all had increased images on TPBS. Either intravenous regional sympathectomy with guanethidine or stellate ganglion block was performed repeatedly. We compared TPBS obtained just before and after this series of sympathetic blocks and evaluated the eventual recovery of function of the hand. In 8 patients, blood flow (phase 1) image of TPBS decreased after the blockade. Of these patients, those who showed almost normalized tracer activity not only on flow image but on blood pool (phase 2) and delayed (phase 3) image, returned to normal. But others with normalized blood flow and still increased activity in blood pool and delayed image, remained with mild contracture of the hand. These results suggest that normalization of blood pool and delayed image on TPBS is a predictor of subsequent recovery after sympathetic blockade in RSD. PMID- 2273546 TI - [Effects of negative extra-thoracic pressure ventilation on extravascular lung water volume and central blood volume in normal dogs]. AB - In negative extra-thoracic pressure ventilation (NETPV), lung water volume and central blood volume (CBV) could increase because of increased venous return and intensified negative interstitial pressure. The effects of NETPV on the extravascular lung water and CBV were examined in ten normal dogs by the double indicator method using Na and cold water. The lung water volume measured by the method (EVTV) was compared with the lung water volume measured by the gravimetric method (EVLW) in 17 dogs. EVTV did not show any significant change in any ventilation modes compared with IPPV. CBV decreased from 21.9 ml.kg-1 to 19.2 ml.kg-1 in CPPV compared with IPPV (P less than 0.05). EVTV correlated well (r = 0.91, P less than 0.001) with EVLW. In normal dogs, NETPV did not change the lung water volume and CBV. NETPV dogs do not seem to have any disadvantage in respect of lung water volume compared with conventional positive pressure ventilations. PMID- 2273545 TI - [Degree and extension of analgesic effect of morphine applied at three different spinal levels of epidural space]. AB - Forty-five patients undergoing total abdominal hysterectomy were randomly divided into three groups. An epidural tube was inserted into one of the following three sites, Th11-12, L2-3, and caudal region. General anesthesia was then maintained with nitrous oxide-oxygen-enflurane, and pancuronium bromide. Morphine hydrochloride 2 mg in 8 ml of normal saline was administered into one of the designated epidural spaces one to two hours before the assumed end of surgery. Postoperative pain was assessed every four hours after the end of the operation until the next morning. Morphine exerted a relatively profound and prolonged analgesic effect in 40% of the Th11-12 group of patients, as well as in 6.7% of the L2-3 and caudal groups. But, supplementary analgesics were necessary in the other patients. No significant differences were found in the degree and extension of postoperative pain, as well as the doses of supplementary analgesics among the three groups. Adverse effects, such as nausea, vomiting and itching, occurred in 30 to 40% of each of the morphine administered groups. Though morphine was applied into different spinal levels, this clinical study did not show any difference in extension of analgesia. The epidurally applied morphine may be distributed widely in the spinal arachnoid space after some time, and may exert an effect on the brain as well as on the spinal nerves. When morphine is administered epidurally one to two hours before the end of a surgical operation, selection of an injection site according to the dermatome level of the skin incision may be unnecessary. PMID- 2273547 TI - [Recovery from cardiac arrest by prostaglandin E1 infusion during emergency open heart surgery]. AB - A 21 day old infant, diagnosed as ASD, VSD, and PDA, was scheduled for an emergency radical operation. After admission, she fell into cardiac failure and was treated with artificial ventilation and infusion of inotropic agents. Anesthesia was induced with fentanyl and maintained with continuous fentanyl infusion and chlorpromazine. Dopamine and dobutamine were administered before she underwent a cor-pulmonary by-pass. At the time of release of aortic clamping, her blood pressure went down and dopamine, dobutamine and isoproterenol were administered. After completion of the cor-pulmonary by-pass, tachy-arrhythmia and hypotension occurred. Digitalis and calcium did not reverse the condition. The thorax was reopened and BP rose. After 15 min, ventricular fibrillation occurred. Defibrillation was carried out, but the heart was arrested. Even with pacing and cardiac massage, cardiac contraction did not resume. However immediately on intravenous administration of PGE1, 40 ng.kg-1.min-1, the heart started to beat. The cause of recovery from cardiac arrest was speculated to be due to reuptake of intracellular Ca2+ by PGE1. We stress therefore, that during and after cor pulmonary by-pass procedures, PGE1 infusion may be beneficial. PMID- 2273548 TI - [Spinal anesthesia in a patient with idiopathic hypertrophic cardiomyopathy]. AB - Transurethral resection of urinary bladder tumor was performed under spinal anesthesia which has been considered to be rather contraindicated in a patient with idiopathic hypertrophic cardiomyopathy. Caution was exercised not to compromise myocardial oxygen supply demand ratio. Central venous pressure (CVP) was continuously monitored and crystalloid solution was infused to maintain CVP in pre-anesthetic level, thereby preventing the reduction in arterial pressure. The patient was hemodynamically stable throughout the operation. This case indicates that if adequate preload could be preserved and hypotension avoided, spinal anesthesia may not be precluded in patients with idiopathic hypertrophic cardiomyopathy. PMID- 2273549 TI - [Anesthesia for surgical intervention in recurrent pneumothorax in a patient with one lung]. AB - A 56 year old man was scheduled for partial resection of the right lung because of many spontaneous pneumothorax episodes. He had received left pneumonectomy for pulmonary tuberculosis and his respiratory function was severely depressed. During anesthesia, pulse oximetry, pulmonary arterial pressure monitoring, pulmonary arterial oximetry in addition to ordinary systemic arterial pressure and electrocardiogram monitoring were performed. Anesthesia was maintained with fentanyl and enflurane, and nitrous oxide was added after thoracotomy. During thoracotomy SpO2 and SVO2 dropped transiently, but intraoperative course was uneventful except an episode of paroxysmal atrial tachycardia. A successful satisfactory anesthetic management of this case depended on the cooperation between anesthesiologist and surgeon, and the appropriate monitoring especially of SVO2 was helpful. PMID- 2273550 TI - [Anesthetic management for surgery of patients with metastatic brain tumors associated with lung tumors]. AB - We had four patients who received anesthesia for metastatic brain tumors. All patients were complicated with primary lung tumors which had caused several respiratory problems. Respiratory failure and intratracheal hemorrhage from lung tumors were the severest complications during and after the operation. Two patients suffered from pneumonia at early postoperative stage and died of respiratory failure within eighty days after the operation. We consider that these preoperative findings of atelectasis and hemosputum are important signs that could predict those severe complications. To avoid postoperative respiratory complications in patients with atelectasis, the anesthetist should perform careful perioperative management such as active preoperative pulmonary physical therapy and should choose anesthetics which do not affect postoperative consciousness and respiration, and should perform intensive postoperative respiratory care. To prevent pulmonary hemorrhage, the fiberoptic bronchoscopy is useful for the diagnosis and the therapy. We also consider that the long operation aggravates postoperative complications. Planning of operation and performing operative procedure in a shortest time possible are also important. PMID- 2273551 TI - [News from Cardiff]. PMID- 2273552 TI - [The anesthesiologist's role in the French emergency medical system]. AB - The present system of French emergency medicine and its philosophy were described from my experience at SAMU (service d'aide medicale urgente). Three factors of emergency medicine; pre-hospital care, emergency transport and emergency information service are managed by anesthesiologists. Anesthesiologists on duty at the tele-medicine center give medical team instructions to start at once. The team is composed of an anesthesiologist, a nurse and an ambulancier. They start to give intensive care medicine to critically ill patients on the spot. The philosophy of SAMU is that doctors should go out of the hospital. Anesthesiologists in the area organize the emergency medical system in France. PMID- 2273553 TI - Long-term observation of cardiac function in Duchenne's muscular dystrophy. Evaluation using systolic time intervals and echocardiography. AB - Cardiac involvement is common in patients with Duchenne type muscular dystrophy (DMD). However, published reports of long-term follow-up studies in the same patients are very rare. The purpose of this study was to clarify the natural course of cardiac dysfunction in DMD, and to analyze the relationship between the deterioration of cardiac function and skeletal muscular function. The cardiac function was serially evaluated for 2-12 years in 34 patients with DMD. The systolic time intervals and echocardiography were used for evaluating the cardiac function. The PEP/ET (pre-ejection period/ejection time) of systolic time intervals significantly deteriorated in 9-12 years (p less than 0.001). The maximal systolic and diastolic endocardial velocity (MSEV and MDEV) and the D/S ratio of echocardiography significantly deteriorated in 5 years (p less than 0.001). The D/S ratio is the ratio of the mean systolic velocity and the mean diastolic velocity of the left ventricular posterior wall. In almost half the patients, the deterioration of these parameters was correlated with that of Swinyard's stage. The Swinyard's functional ability stage demonstrates the grade of the skeletal muscular dysfunction. However, there was no correlation between the deterioration of cardiac function and Swinyard's stage in the other half of the patients. Correlation coefficient in the whole group was 0.32 (p = n.s.) between the PEP/ET and Swinyard's stage, and was -0.15 (p = n.s.) between the D/S ratio and Swinyard's stage. Although the mean left ventricular ejection fraction calculated using echocardiography was slightly decreased for 5 years, no significant change was detected in the whole group. One patient had progressive deterioration of left ventricular function despite mild skeletal muscular dysfunction, and died from congestive heart failure. The cardiac dysfunction was predominant. We named it 'cardiac type' DMD. Since deterioration of cardiac function was not always correlated with deterioration of skeletal muscular function (Swinyard's stage), cardiac function must be carefully monitored in patients with DMD. PMID- 2273554 TI - Short-lasting hemodynamic and clinical benefits from percutaneous balloon valvuloplasty for calcific aortic stenosis. AB - In order to evaluate the short- and mid-term results of percutaneous aortic balloon valvuloplasty, 40 consecutive elderly patients, who had undergone balloon valvuloplasty for calcific aortic stenosis, were prospectively followed up by means of clinical and echo-Doppler examinations. Although valvuloplasty often dramatically improves hemodynamics and relieves symptoms, these benefits seem to be short-lived in most cases. Restenosis, defined as a loss of 50% or more of the increase in aortic valve area obtained by the dilatation, has a very high rate of occurrence. Aortic balloon valvuloplasty should therefore be reserved for truly inoperable cases and can be performed in hemodynamically unstable patients, who may later undergo surgery. PMID- 2273555 TI - Aortic and pulmonary input impedance in patients with cor pulmonale. AB - The hydraulic load of the right and left ventricles and the clinical effects of nifedipine were evaluated in 8 normal subjects (mean age: 55 years) and 8 patients with cor pulmonale secondary to chronic obstructive lung disease (mean age: 57 years). It was found that there were differences in the right ventricular resistance (174.62 +/- 25.96 vs 468.57 +/- 178.81 dyne/sec/cm-5), first zero crossing frequency (3.62 +/- 0.34 vs 6.07 +/- 3.56 Hz), steady power (218.95 +/- 32.25 vs 359.44 +/- 37.46 mW) and total power of right ventricle (275.81 +/- 36.18 vs 440.46 +/- 85.16 mW) between the normal and cor pulmonale patients, respectively. However, no significant changes in characteristic impedance, pulsatile power or aortic impedance were observed in the right pulmonary artery. After administration of nifedipine to patients with cor pulmonale, there were significant changes in resistance (468.57 +/- 178.81 vs 256.36 +/- 178.56 dyne/sec/cm-5), steady power (359.44 +/- 37.46 vs 225.51 +/- 114.64) and total power (440.46 +/- 85.16 vs. 289.27 +/- 50.85) of the pulmonary artery, respectively. Otherwise there were no significant changes in aortic input impedance or characteristic impedance of right pulmonary artery and pulsatile power. In conclusion, we found that: 1) the hydraulic vascular load in the right ventricle was higher in patients with cor pulmonale, 2) characteristic impedance that was not increased in cor pulmonale patients may be due to a dilated pulmonary artery, 3) there was no impedance mismatch between left ventricle and systemic arterial system in patients with cor pulmonale, and 4) by reducing the pulmonary vascular resistance through nifedipine administration, the total external right ventricular power might be reduced, without affecting the proximal pulmonary arterial compliance. PMID- 2273556 TI - Quantitative analysis of high-frequency components of signal-averaged QRS complex in Chinese patients with acute myocardial infarction. A prospective study for prediction of ventricular tachycardia. AB - A prospective study was undertaken of the high-frequency components of the terminal portion of the QRS complex in 38 Chinese patients with acute myocardial infarction (AMI) (mean age 62 +/- 5.6 years) within the first week after the acute event (5.5 +/- 1.2 days). Another 44 normals served as controls (mean age 57 +/- 9.6 years). The electrocardiogram was averaged at a filter band pass of 80 300 Hz. The low voltage span (LVS) of the signals less than 40 microV in the terminal portion of QRS, the root-mean-square (RMS) voltage (V) of terminal 40 msec of the QRS complex, and the total duration of signal-averaged QRS vector complex were measured in both the normal subjects and patients. The LVS was abnormally prolonged in 16 of 38 patients (42%), and in only 16% of normals (p less than 0.05). The RMS-V was abnormal (less than 25 microV) in 29 of 38 patients (76%), and in only 20% of normals (p less than 0.0005), and the signal averaged QRS vector complex was abnormal (greater than 120 msec) in 26 of 38 patients (68%), and only 9% of normals (p less than 0.005). There was no significant correlation between any of the signal-averaged parameters, the site of AMI and total creatine kinase (CK) or CK-MB values. The signal-averaged parameters also showed no relationship to either the cardiothoracic (C/T) ratio or the left ventricular ejection fraction, determined by the Tc-99 m pertechnetate first pass blood pool technique. Holter ECG monitoring was performed twice in all AMI patients, at 7 to 18 days after the acute event (12 days average) and 3 weeks after the first recording. There were only four episodes of non-sustained ventricular tachycardia (VT), all during the second monitoring period. Three episodes (10%) occurred in patients with positive late potentials (LPs), defined by an RMS-V less than 25 microV in the terminal portion of QRS vector; one episode (11%) occurred in patients with negative LPs (9 patients). Although the incidence of LPs is significantly higher in patients with an AMI than in normal controls, the LPs detected by body surface signal-averaged ECG did not predict the occurrence of in- and out-of-hospital VTs. Thus, after AMI, Chinese patients may not be as prone to develop VTs as are Caucasians. Furthermore, the appearance of LPs is independent of cardiac size and left ventricular ejection fraction. PMID- 2273557 TI - Influences of autonomic changes on the sinus node recovery time in patients with sick sinus syndrome. AB - To assess the relative contribution of sympathetic and vagal influences on diurnal variation of sinus node recovery time (SNRT) in sick sinus syndrome (SSS), the diurnal changes of SNRT and the effects of propranolol and subsequent atropine on SNRT were examined in 39 patients with SSS. SNRT was measured before and after intravenous propranolol (0.1 mg/kg), and after subsequent intravenous atropine (0.02 mg/kg) in the cardiac catheterization laboratory. After completion of the electrophysiologic studies in the laboratory, SNRT was measured at 0 a.m. (midnight), 6 a.m. and 12 noon on the following day in the ward. After propranolol, SNRT was prolonged in 22 of 26 patients and shortened in 4 patients. After subsequent atropine, SNRT was prolonged in 5 of 26 patients and shortened in 21 patients. The patients with SNRT longer than 3 sec had a tendency to have greater diurnal variation of SNRT than those with SNRT less than 3 sec. A strong correlation (r = 0.98) was found between SNRT after propranolol and the longest SNRT in a 24-hour period. A difference of SNRT between after propranolol and after subsequent atropine was significantly correlated (r = 0.88) with a difference between the longest and the shortest SNRT in a 24-hour period. These results suggest that the diurnal changes in SNRT are regulated by the autonomic nervous system in SSS. SNRT after propranolol may be useful in estimating the longest SNRT in a day. PMID- 2273558 TI - Proteolysis of myosin and troponin in human myocardium of elderly subjects. AB - Actomyosin was prepared from human myocardium and its protein composition was examined by SDS-polyacrylamide gel electrophoresis. For some preparations, particularly actomyosin isolated from elderly subjects, a high molecular weight (HMW) band (identified as a breakdown product of myosin heavy chain) appeared, while the troponin-T subunit decreased. Myofibril associated protease (MFP) activity showed no significant difference as a function of proteolysis. In agreement with the proteolysis of troponin-T and myosin, the Ca2+ sensitivity of Mg2(+)-ATPase activity decreased while the extent of the stimulation of Ca2(+) ATPase by N-ethylmaleimide remained unchanged. This type of proteolysis would affect the Ca2(+)-dependent regulation of muscle contraction but not the contractility per se. PMID- 2273559 TI - The pressure-volume relation and the mechanics of left ventricular contraction. AB - The left ventricle is represented as an elastic thick-walled cylinder contracting symmetrically. The force generated by the active state of the myocardium in the radial direction is represented by body force (force/unit volume) and is included in the mathematical formalism that describes the contraction of the left ventricle. An equation for the P-V relation in the left ventricle is derived and various applications to study cardiac mechanics are discussed. The results obtained tend to demonstrate that the active force generated by the myocardium during an ejecting contraction reaches its maximum value near the end of the systolic phase, when the slope E of the P-V line reaches its maximum value Em, and that it is related to the peak isovolumic pressure. PMID- 2273561 TI - Subacute rupture of the free left ventricular wall following acute myocardial infarction. Successful surgery in a case. AB - Free left ventricular wall rupture following acute myocardial infarction usually results in cardiac tamponade and sudden death. Occasionally, the bleeding into the pericardial sac is arrested by the surrounding pericardial tissue causing formation of a pseudoaneurysm. The case herein reported presented with a refractory pericardial effusion 1 month after an anterior myocardial infarction. While echocardiography failed to reveal a pseudoaneurysm or to localize a rupture, cineventriculography disclosed the diagnosis of a minimal rupture of the left ventricular free wall. The patient was successfully treated by surgery. PMID- 2273560 TI - Cardiovascular effects of 2-amino-N-(2,6-dimethylphenyl)-N-[3-(3 pyridyl)propyl]propionamide dihydrochloride (Ro 22-9194) in the isolated, cross perfused atrium of the dog. AB - The cardiovascular effects of 2-amino-N-(2,6-dimethylphenyl)-N-[3- (3 pyridyl)propyl]propionamide dihydrochloride (Ro 22-9194) were investigated in the canine isolated atrial preparation perfused with arterial blood from another donor dog. Intravenous administration of Ro 22-9194 (0.3-3 mg/kg) reduced heart rate and systemic arterial blood pressure of the donor dog. Simultaneously, in the isolated atrium perfused with donor's blood, negative chronotropic and inotropic responses were induced in a dose-dependent manner. Direct administration of Ro 22-9194 (1-300 micrograms) into the sinus node artery of the isolated atrium induced negative chrono- and inotropic responses and a transient increase in coronary blood flow in a dose-related manner. Mexiletine (1-300 micrograms) also induced negative chrono- and inotropic responses. The potency of Ro 22-9194 for negative cardiac effects was similar to that of mexiletine. The negative cardiac effects of Ro 22-9194 were not modified by atropine in doses which significantly inhibited the cardiac effects of acetylcholine. Ro 22-9194 did not affect the cardiac responses to norepinephrine and to acetylcholine significantly. These results suggest that Ro 22-9194 has non-cholinergic cardiac depressant properties with its vasodilating action, and it has neither anti adrenergic nor anti-cholinergic actions on the dog heart. PMID- 2273563 TI - [Zygomycosis caused by Cunninghamella bertholletiae]. AB - Cunninghamella bertholletiae, an uncommon cause of human fungal infection, has been reported with increasing frequency in recent years in Western countries. We report a case of acute myelogenous leukemia terminated by an uncommon complication of zygomycosis caused by C. bertholletiae, which seems to be the first human case reported in Japan. In this case, the fungus disseminated many organs, including the thyroid gland. PMID- 2273562 TI - [The study of cases with infection by methicillin-resistant Staphylococcus aureus]. AB - The purpose of this study was to evaluate the risk factors which lead to death due to highly critical staphylococcic enteritis manifested by high fever, large amount of watery diarrhea and gastric secretion with leukopenia and lymphocytopenia after surgical procedures. We experienced eight cases of severe staphylococcic enteritis by methicillin-resistant Staphylococcus aureus (MRSA) occurred in the early days after operation from 1986 to 1990. Seven out of eight cases underwent gastrectomy due to gastric cancer. Oral antibiotics were administered in five out of eight cases as the preparation of gastrointestinal tract. Five had been injected the third-generation cephalosporin (CZX) as prophylactic antibiotic administration. In hematological examination, leukopenia and lymphocytopenia were observed in five cases (62.5%) who died soon after operation. So as to prevent the occurrence of MRSA enteritis, it is important to avoid using third-generation cephalosporin after gastrectomy. PMID- 2273564 TI - [Infection with Pseudomonas pseudomallei]. AB - Melioidosis, a severe, often fatal disease caused by infection with Pseudomonas pseudomallei, has been thought to be a rare endemic disease relatively limited to the areas 20 degrees on either side of the equator. However, an increasing number of people travelling to these areas are reportedly suffering from this disease. It is timely to review this disease for doctors who are unfamiliar with this disease. P. pseudomallei, first discovered by Whitmore and Krishnaswami in 1912, is a gram-negative aerobic rod, motile due to polar flagella, isolated from soil and natural waters in endemic areas, and presumably transmitted to human beings through skin abrasion, ingestion and inhalation. Associated underlying conditions must be searched for, such as diabetes mellitus and chronic renal failure. Clinical classification ranges from disseminated septicemic melioidosis, the most serious form, to subclinical melioidosis, the least serious form. Disseminated septicemic type is associated with high fever, multiple organ lesions with septic shock and high fatality rate within a few days after symptoms develop. This type of infection requires prompt institution of antimicrobial therapy as well as surgical intervention such as drainage. Antimicrobial agents should be carefully selected according to the susceptibility results of the isolates. During the suspected stage, ceftazidime is a drug of choice. Subclinical melioidosis associated with positive serologic test alone should be closely followed up against the potential reactivation of dormant infection with P. pseudomallei. We must certainly be aware of melioidosis and diagnose melioidosis as early as possible by completing the initial routine diagnostic procedures to febrile patients. PMID- 2273565 TI - [Lyme disease]. AB - Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi. Clinical manifestations typically begin with characteristic skin lesions, erythema (chronicum) migrans. Weeks to months later, some patients develop the second stage of the illness characterized by neurologic abnormalities, migratory joint pain, cardiac involvement. Months to years later, in many patients the disease progresses to the third stage of manifestation such as chronic arthritis, chronic encephalomyelitis, acrodermatitis chronica atrophicans and keratitis. Zoonotic infection with B. burgdorferi is also widespread within endemic regions among domestic as well as wild animals. The diagnosis is based on clinical and epidemiological findings in most patients, particularly those with erythema migrans or tick bites. Detection of specific antibodies to B. burgdorferi is a useful confirmatory test in many patients. In atypical cases, a positive test result can be valuable for determining the diagnosis. However, serologic testing in Lyme disease is not yet standardized and the results obtained from different assay systems or commercial kits may vary. Moreover, because of poor agreement in sensitivity and/or specificity, data obtained from different laboratories are not comparable. We emphasize that serologic findings must be interpreted with caution; the physician must beware of its strengths and limitations. PMID- 2273567 TI - [Clinical laboratory works and taxonomy in bacteriology]. AB - Taxonomy is the basic stand point for every field of bacteriology and provides a common language to each worker and researcher in bacteriology throughout the world. Proper identification of isolates from human pathological specimens or from hospital environments is one of the five principal fields of bacterial taxonomy. Before the establishment of classification and stabilization of nomenclature, any isolate can not be identified. Collection of unidentifiable strains is the starting point of new taxonomic investigation. Doctors in medical fields tend to be too much concerned to the infrasubspecific subdivisions, such as serological classification, toxigenicity, resistance to antimicrobics, rather ignoring the classification above the rank of subspecies. Doctors who take care patients and workers in clinical bacteriology laboratories should recognize the importance of bacterial taxonomy in general and use the necessary information in taxonomy selectively. PMID- 2273566 TI - [Legionellosis]. AB - Although increasing attention is being given to Legionella pneumonia in Japan, reports of solitary onset of this disease are scant in Japan. The patient, from whom L. dumoffii was isolated, was a 59-year-old male with no underlying disease. He visited our hospital because of fever and cough, and was admitted to our department for X-ray findings consistent with pneumonia. After admission, pulmonary lesions spread rapidly, and based on the suspicion of Legionella pneumonia, drugs such as EM, RFP and MINO were used. However, the patient died on the 26th hospital day. L. dumoffii was isolated from specimens obtained by airway aspiration before death and specimens of lung abscess and airway discharge obtained during autopsy (7 specimens in total). In addition, the L. dumoffii antibody titer in the serum became elevated. This is the first case of L. dumoffii pneumonia reported in Japan. The other case was in an 81-year-old male with underlying disease. He was admitted urgently with suspected pneumonia but died on the following day. L. pneumophila serogroup 5 was isolated from autopsied lung tissue. Fatality is high for this disease, making early diagnosis and treatment with appropriate antibiotics essential. Physicians should bear in mind the possibility of this disease and request the necessary laboratory tests in suspected cases without delay. PMID- 2273568 TI - [Discriminate function of diabetes mellitus (DM) for screening test by serum 3 lipids and glucose]. AB - The purpose of this study was to establish a program to differentiate diabetic patients in computerized health check data using serum lipid test data. We selected 4 items (TC, FC, TG and Glu) as a marker of clusters for further study on the strength of data obtained from cluster analysis using chemical data obtained on 134 patients. Next we tried principal analysis of the 4 items and computed parameters of component 1 & component 2, and obtained a function (D) to discriminate DM. Function (D) is read from comp. 1 and comp. 2. Comp. 1 = (0.89 x TC + 0.95 x FC + 0.75 x TG + 0.24 x Glu) Comp. 2 = (-0.26 x TC -0.21 x FC + 0.27 x TG + 0.93 x Glu) D = (0.2 x comp. 1 + comp. 2-160) DM patients show D greater than = 0 and non-DM patients D less than 0. We applied data on 587 patients (including of 43 DM) incorporating function (D) to check the property. The results proved it useful as a screening test for diabetic patients. The parameters of function (D) are influenced by inter-laboratory differences. However, our parameters were still effective. Data obtained from other laboratories incorporating our parameter gave a diagnostic quality of more than 70%. PMID- 2273570 TI - [The sensitivity of 1,000 human tumors to antitumor drugs using the succinate dehydrogenase inhibition (SDI) test]. AB - The chemosensitivity was evaluated by the in vitro succinate dehydrogenase inhibition (SDI) test in 1,000 human tumors including 237 gastric cancers, 116 colorectal cancers, 113 hepatoma and 534 others. These tumor cells were exposed to 5 kinds of antitumor drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cis-platinum (DDP). After exposure to the antitumor drugs, cell viability was assessed with colorimetric assay, based on the ability of succinate dehydrogenase (SD) in living tumor cells to reduced a tetrazolium (MTT) to a formazan. The chemosensitivity was determined to be positive when the SD activity of drug exposed cells decreased to below 50% of that of control cells, on day 3 of exposure. The chemosensitivity varied in the tumor tissues. The chemosensitivity of metastatic lesions of lymph nodes were higher than that of the primary lesions, while metastatic liver tumors had lower sensitivity than the primary lesions. The intra-tumorous distribution of SD activity in 12 human gastric cancers were compared with normal adjacent tissues using histochemistry. Seventy-five % (9/12) of gastric cancer tissues had higher SD activity than normal adjacent tissues. The SDI test is rapid and simple method to predict the sensitivity test of various human tumors to antitumor drugs. PMID- 2273569 TI - [Quick radioimmunoassay for plasma immunoreactive insulin (IRI)--application for localizing occult insulinoma during operation]. AB - A quick RIA for IRI was developed which can be applied for localizing occult insulinoma during extirpation of the tumor. We used anti-insulin antibody insolubilized with bacterial cell wall. The standard solutions were prepared by dissolving porcine insulin in human plasma containing low level of IRI. By use of this assay IRI in plasma samples are assayed within 45 min for 20 samples including standard samples. The coefficient of variation of intra- and inter assay were 9-19% and the recovery tests were 70-120%. The assay has a sensitivity of 10 microU/ml. The obtained IRI values by this method correlated well with those by the usual method (Insulin RIA Bead) (y=1.0 x -0.2, r = 0.98). A clinical case with insulinoma was shown in which the localization of the tumor was diagnosed from IRI levels in various portions of splenic vein assayed by this method during the operation and the tumor was extirpated successfully. PMID- 2273571 TI - [Laboratory tests in primary care medicine: "essential laboratory tests" (1). Urinalysis]. AB - Japan Society of Clinical Pathology has formed a committee dealing with "lab. tests in primary care medicine". As the first step, they made "Essential Lab. Tests" which were composed of simple qualitative bed-side tests such as urinalysis, Complete blood count (CBC: Hb, Ht, WBC, RBC), CRP, or ESR (Erythrocyte sedimental rate), A/G ratio and biochemical tests if necessary (Table 1). We have performed "Essential Lab. Tests" on 1,026 outpatients who visited General Medicine Clinic for the first time. They consisted of 456 male (age 13-81), and 526 female (age 10-85). This report is the result of urinalysis from "Essential Lab. Tests" of 1,026 patients. 1) The result showed that overall positivity of the urinalysis was 21.3% (when more than one item of the qualitative tests was positive). 2) There was distinctive difference in the positivity of the urinalysis between the sex; i.e. protein and glucose were about twice frequently positive in male, where as occult blood and WBC (Esterase reaction) were 2-3 times more positive in female. 3) Urine protein shows positive in the individual 10-20 yrs old and more than 50 yrs old in both sexes. 4) Glucose was positive in over 40 yrs in male, and occult blood, 40-50 yrs or older in male. 5) WBC shows positive in all age groups in female and 50 yrs or older in male. 6) Positive WBC patients did not necessarily reflect urinary infection in female but nitrites roughly corresponded with urinary WBC in male of 50 yrs or older, meaning probable urinary infection associated with prostatic hypertrophy. 7) Abnormality of urinary sediment corresponded to the positive occult blood and WBC Erastase. 8) Urinalysis is an useful method of screening in primary care medicine. PMID- 2273572 TI - [Measurement of the DNA content in morphologically identified cells on a Wright Giemsa stained smear]. AB - 4',6-Diamidino-2-phenylindole (DAPI) staining was applied to measuring nuclear DNA contents of single cells previously identified on a Wright-Giemsa stained smear. The smear was first photographed and the location of each cell was mapped. The smear was then destained with 50% acid ethanol and absolute methanol, and restained with DAPI (pH 7.4) at 4 degrees C. Blue fluorescence was observed in the nucleus, and the intensity of this fluorescence was proportional to the amount of DNA, with the lowest coefficient of variation of 3.6% in the case of staining the peripheral lymphocytes for 30 min. This method is useful for measuring DNA contents in heterogeneous cell populations. PMID- 2273573 TI - [Three-dimensional structures of epidermal melanocytes in normal human skin]. AB - To elucidate the three-dimensional distribution and cell structure of human epidermal melanocytes in vivo, normal skin specimens were analyzed by a stereographic and stereometric method using computer. After brief fixation, dihydroxyphenylalanine (DOPA)-melanosome reaction method was performed. Specimens were then post-fixed with glutaraldehyde and osmium tetroxide, dehydrated, and embedded in Epon. Serial sections were obtained in an ultramicrotome and stained with toluidine blue. Epidermal melanocytes were stained dark brown by this method. From the serial two-dimensional figures of the melanocytes, three dimensional images of their cell structures were reconstructed using a computer stereography ++ system (Cosmozone 2SA, Nikon, Tokyo). Stereographicaly, the epidermal melanocytes were distributed unevenly on a waving epidermal basement membrane; some of them often gathered. The melanocytes showed spherical cell bodies extending several thin processes, whereas epidermal basal keratinocytes showed ellipsoidal cell bodies. By stereometry, the melanocytes had a significantly larger cytoplasm and a smaller nucleus in volumes compared with the basal keratinocytes. Our stereological method may prove to be important in determining three-dimensional features of normal or abnormal melanocytes. PMID- 2273574 TI - [Analysis of anti HMW.MAA antibodies in sera of melanoma patients using antiidiotypic monoclonal antibodies]. AB - The immunogenicity in patients with melanoma of three high molecular weight melanoma associated antigens (HMW.MAA) defined by murine monoclonal antibodies (MoAb) was investigated. For this end sera from patients with melanoma (stage I, IV) and normal individuals were tested by inhibition assay and sandwich assay using antiidiotypic MoAb to anti HMW.MAA MoAb. In inhibition assay, sera were tested for their ability to inhibit the binding of murine antiidiotypic MoAbs to biotin conjugated anti HMW.MAA MoAbs. Some of the sera from patients with melanoma significantly inhibited the binding of antiidiotypic MoAb to anti HMW.MAA MoAb in comparison with that from normal individuals. In sandwich assay, sera were tested for their ability to bind to precoated murine antiidiotypic MoAb and to biotin conjugated anti HMW.MAA MoAbs. Positive findings suggest the existence of anti HMW.MAA antibodies in sera were showed in several sera from the patients, which were less in frequency than that in inhibition assay. These results suggest that HMW.MAA could elicit the immune response in some melanoma patients and also suggest that the assay anti HMW.MAA MoAb in sera will help us to understand the prognosis of the patients and to evaluate the usefulness of treatment with antiidiotypic MoAb as vaccine therapy. PMID- 2273575 TI - [Results of patch test using mite components in atopic dermatitis (AD) patients. 1st report. "As is patch test" using crushed mites]. AB - As is patch test using crushed live mites and crushed dried dead mites of Dermatophagoides pteronyssinus (D.p.), Dermatophagoides farinae (D.f.), & Tryophagus ptrescentiae (T.p.) was performed on 49 AD patients and 18 control patients suffering from dermatitis other than AD. RESULTS: 1) with crushed dried dead mites all patients showed negative reactions but with live mites 11 among 49 AD patients were positive (22.4%); 2) female mites were more positive than males at the rate 8:1; 3) with cases positive to mites, (a) D.p. was positive in all 11 positive cases (100%), (b) D.f. was negative in 5 cases (0%), and (c) T.p. was positive in 2 cases among 4 (50%); 4) because of the pathological manifestations of spongiosis and the infiltration of histiocytes and lymphocytes, the possibility of contact allergy to mite elements was suggested, as a mechanism of atopic dermatitis. PMID- 2273576 TI - [Result of "as is patch test" using mite elements in atopic dermatitis (AD) patient. 2nd report, "Mite lipid"]. AB - The antigenicity of mite lipid was studied, taking atopic dermatitis as an allergic disease. Lipid was extracted from Dermatophagoides pteronyssinus (Dp) and D. farinae (Df). It was tentatively designated a mite lipid antigen (Dp-L, Df L), and then a patch test was performed. An extract from animal food (LC) and acetone were used as the controls. With only Dp-L, a positive reaction of more than one plus (+) of the ICDRG standard was noted in 3 out of 21 cases of AD. Histology of the above-mentioned positive cases revealed spongiosis and infiltration of small round cells in the upper dermis along with scattered eosinophiles. Leu 6 positive cells were noted frequently in the epidermis and dermis. The lipid components of Dp-L were made up mostly of phospholipid and triglycerides+, and lipoprotein was not contained. Judging from the findings above it appears necessary to study not only protein but also lipid in connection with the mite antigenicity++ in AD in the future. PMID- 2273577 TI - [Significance of HLA-DR+ T cells and natural killer (NK) cells in the peripheral blood lymphocytes of alopecia areata (AA)]. AB - HLA-DR+ T cell and NK cell subsets in peripheral blood lymphocytes of patients with AA were investigated. The percentages of HLA-DR+ T cell and NK cell subsets from a mild condition of patchy AA and an acute condition of alopecia totalis, for which hair regrowth occurred frequently with ease, were similar to those of the normal control. On the other hand, the percentages of HLA-DR+ Leu3a+ cells HLA-DR+ Leu2a+ cells and Leu7-Leu11+ cells from a severe condition of patchy AA and alopecia universalis, for which hair regrowth did not easily occur, were significantly higher than those of the normal control. The increase in the percentages of HLA-DR+ Leu3a+ cells, HLA-DR+ Leu2a+ cells and Leu7-Leu11+ cells from the severe condition of patchy AA and alopecia universalis was lessened and normalized by treatment with betamethasone. These findings suggest that the auto immune disorders of HLA-DR+ T cell and NK cell may play important roles in disease activities related to severe patchy AA and alopecia universalis. PMID- 2273578 TI - [Pigmented spindle cell nevus and pigmented Spitz nevus--clinical and histopathological study on pigmented Spitz nevus, and its differentiation from early melanoma by fluorescence method and measurement of 5-S-CD level in the lesion]. AB - On the basis of clinical and histopathological studies on 17 patients who had been diagnosed as having pigmented Spitz nevus (PSN), pigmented spindle cell nevus (PSCN) was surmised to be a type of pigmented Spitz nevus. In order to distinguish pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma, 5 PSCN cases and 12 PSN cases were analyzed by the fine-needle aspiration fluorescence method, touch fluorescence method and measurement of the 5-S-CD level in the lesion. With the touch fluorescence method, fluorescent tumor cells were detected in one case of PSN. With the fine-needle aspiration fluorescence method, fluorescent tumor cells were detected in one PSCN case and 2 PSN cases. In comparison with fluorescent melanoma cells, the detected fluorescent tumor cells were smaller in size and number and resembled melanocytes. The 5-S-CD level in the lesion was 50 ng/mg or less in all cases, whereas the level in melanoma is known to be a high 100 ng/mg or more. In the final analysis, measurement of the 5-S-CD level in the lesion was concluded to have the greatest utility for differential diagnosis of pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma. PMID- 2273579 TI - [A survey of the social and psychological effects of psoriasis]. AB - 338 patients with psoriasis (male: 213, female: 125) who have been treated in our department from 1979 to 1988 answered a questionnaire concerning social and psychological effects of the disease. The mean age of onset was 33 years; 35 years for the male and 29 years for the female. Social and emotional morbidity was present for many patients despite the access to modern treatments. The worst feeling about having psoriasis was general appearance of the skin (41.7%), itching (19.5%), flaking of the skin (16.9%) and time-consuming or messy treatment programs (13.3%). A large percentage of patients avoided common social activities, for example, communal baths, swimming, and sports. Triggering factors of psoriasis were climate (60.3%), stress (46.9%), sleeping disturbance (34.6%), irregular life (32.2%), and low humidity (22.5%). 18.6% of patients were affected in choosing the occupation by having psoriasis. Many patients felt stigmatized as the disease is contagious or genetic. Most of the patients learned psoriasis through doctors, however, 75.7% of them wanted to get more informations. Finally, since only 26.3% of patients were satisfied with current therapeutics, dermatologists seem to be too self satisfied with present managements. It is important for us to understand what the patients are really suffering from and what the patients really want. And, it also is important to make efforts for a better understanding of psoriasis in society. PMID- 2273581 TI - [Adenosquamous carcinoma of the skin--ultrastructural and immunohistochemical studies]. AB - Adenosquamous carcinoma, which arose on the face of a 83-year-old woman was studied ultrastructurally and immunohistochemically. The tumor was composed of squamoid cells and mucinous cells including signet-ring cells. Electron microscopically, the tumor cells developed numerous microvilli on the cell surface, and had tonofilaments, well-developed rough endoplasmic reticulum and secretory granules of a mucinous type in the cytoplasm. The signet-ring cells had a large intracytoplasmic cavity containing fine fibrillar, mucin-like substance. Occasionally observed were intercellular masses, around which the tumor cells formed hemidesmosome-like and basal lamina-like structures. Immunohistochemical staining revealed foci of positive reaction for laminin surrounding the tumor cells. The tumor cells displayed positive stainings for stratified-epithelial keratins, but not for simple-epithelial keratins. From these findings, it was concluded that the present tumor might be a carcinoma of squamous cell origin, showing a mucinous metaplasia. PMID- 2273582 TI - [Reconsideration on neck-shoulder-arm syndrome]. PMID- 2273580 TI - [Cutaneous infection by Mycobacterium fortuitum biovariant "third group"--a case report and bacteriological examination of the isolate]. AB - A 22-year-old woman with ten-year history of atopic dermatitis first noticed an erythematous ++, indurated, and fluctuant lesion on her back six month prior to visiting our hospital in February 1989. The dusky red skin lesion gradually spread to the right side of her trunk and drained small amount of purulent or serosanguineous fluid. A skin biopsy specimen showed mixed pattern of nonspecific inflammatory infiltrate and granulomatous infiltrate in the dermis. A culture of the biopsy specimen showed a rapidly growing atypical acid-fast bacteria, which was identified as Mycobacterium fortuitum and classified as biovariant "third group" by positive growth on mannitol and inositol. Minimum inhibitory concentrations (MICs) of different antimicrobial agent using broth medium showed that the isolate was susceptible to the new quinolones such as ofloxacin and ciprofloxacin. The patient responded to treatment with doxycycline followed by with ofloxacin. Subspecies classification and antibiotic susceptibilities were discussed with special reference to treatment of rapidly growing mycobacteria. PMID- 2273583 TI - [Genotoxicity of synthetic dyes in the umu test using Salmonella typhimurium TA1535/pSK1002 (II). Results of examination of basic dyes]. AB - In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carried out with five doses of basic dyes (400, 120, 40, 12, and 4 micrograms/ml). The samples showing beta-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing beta-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13(h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes. PMID- 2273584 TI - [Mental health care for mentally ill employees. Part 2. Follow-up and outcome of mental disorders]. AB - A mental health program was commenced in 1957 in an electric power company which has about 360 offices and 17,000 employees scattered throughout Kyushu. During a period of 30 years from 1957 to 1986, a total of 949 mentally ill employees sought consultation regarding various mental health problems. Following the initial interview, periodic follow-up study was made on them. The results showed that year-end prevalence rate increased with continuation of mental health work and the rate reached 0.73% in the recent 5 years. At the end point of the study, 358 employees (37.7% of the subjects) were working in the company and 591 cases (62.3%) had retired. The number retiring before reaching retirement age was 228 cases (24.0%) and in particular, retirement due to death and retirement due to disease in the subjects were higher in rate than those of all employees of the company. PMID- 2273585 TI - [Breakthrough time of organic solvent vapor on activated carbon under unsteady state conditions]. PMID- 2273586 TI - [Relationship between serum cholesterol level and liver function tests in male workers in an urban area]. PMID- 2273587 TI - [Development of Japanese edition of Neurobehavioral Evaluation System (NES) and WHO Neurobehavioral Core Test Battery (NCTB): with assessment of reliability]. PMID- 2273588 TI - [Measurement of oil mists by a portable sampler and subjective symptoms among machine workers: a field investigation of machine workshops]. AB - Machine oils are widely used in metal processing and many workers are exposed to oil mists in the work environment. Some investigators have pointed out such health hazards due to prolonged exposure to oil mist as respiratory disorders, dermatitis, and possible carcinogenesis. In Japan, a permissible limit of oil mists of 3 mg/m3 was recommended in 1977 by the Japan Association of Industrial Health (JAIH) mainly based on the hazardous effects on the respiratory system. After this recommendation was made, only a few studies have been made on the measurement of oil mists and on the health effects in machine workers to determine whether the permissible limit is justifiable or not. In the present study, the levels of oil mists in the air of machine workshops were measured together with personal exposure levels by personal samplers. Oil mists were collected by a sampler head with 2 stages which enabled differentiation of distribution of particulates between larger than 10 microns and 2-10 microns in size. Oil components collected on the stainless steel stages were washed out by sonication in CCl4 solution and measured by an oil meter with infra-red spectrometry against a standard solution of heavy oil class B according to procedures reported elsewhere by the authors. Questionnaire surveys were also conducted on 308 male machine workers composed of 221 workers exposed to oil mists and 87 nonexposed controls. The questions were composed of five items about air quality in the work environment and 18 subjective symptoms during work and daily lives. The symptoms included nasopharyngeal, muco-dermal, gastrointestinal and neuro-muscular symptoms. Statistical analysis was made by the Manthel Haenszel method for a comparison of "yes" rates of complaints between the exposed and the non-exposed by adjusting the underlying confounding factor of age distribution. 1. The levels of oil mists measured here ranged from 94 to 813 micrograms/m3 in the ambient air and from 107 to 483 micrograms/m3 of personal exposure. There was no obvious difference between the level in the ambient air and that of personal exposure. All these measured levels were under the permissible limit (3 mg/m3) recommended by JAIH in 1977. 2. The observed distribution of particulate size of oil mists from 2 to 10 microns referred to as respirable size was 32.8 +/- 16.1% generated from the grinding machines using water-soluble type of machine oils and 50.0 +/- 12.4% from those using insoluble type.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2273590 TI - [Recommendations on permissible exposure levels (1990)]. PMID- 2273589 TI - [Raynaud's phenomenon and cutaneous changes due to hand-arm vibration]. AB - Vibration of hand-held tools is considered to induce disorders in the peripheral circulation, peripheral nerve and organs, muscles, bones and joints (vibration syndrome). Above all, Raynaud's phenomenon is known as a prominent sign of vibration syndrome. This paper describes the findings obtained from the observation of the skin of the hands exposed to vibration and evaluates the relation between Raynaud's phenomenon and cutaneous changes. A total of 124 chain saw workers in a forestry company in Gifu Prefecture were investigated in connection with compulsory health examination. In medical occupational interview, every worker was asked whether he had any experience of Raynaud's phenomenon or not. Moreover, the following symptoms of the skin and nails of the hand(s) were examined: 1. sclerodactylia, 2. pitting scar, 3. edema, 4. erythema around the nail, and 5. elongation and bleeding of proximal nailfolds and cuticles. To determine whether vibration induces the above mentioned cutaneous changes, the relation between the prevalence of the changes and the duration of exposure to vibration was assessed. The workers were classified into four groups by duration of exposure to vibration (in intervals of 10 years). The evaluation was made by comparing the prevalence of cutaneous changes between the workers with Raynaud's phenomenon and those without it. Subjects were restricted in age from 40 to 59 years. There was a significant relationship between age and duration of exposure (p less than 0.001). The prevalence of Raynaud's phenomenon was significantly high among the workers in the fifties (15.8%). The prevalence of Raynaud's phenomenon was significantly increased in workers with longer exposure. The prevalence of Raynaud's phenomenon was 6.9% in workers in the forties. Though the prevalence of sclerodactylia and elongation and bleeding of proximal nailfolds and cuticles was higher in workers in the fifties than those in the forties, (1. 34.7% in the 50 s, 24.1% in the 40 s 5. 27.4% in the 50 s, 17.2% in the 40 s), no relation could be demonstrated between the duration of exposure and the prevalence of cutaneous changes. There were no significant differences in the prevalence of cutaneous changes between the workers with Raynaud's phenomenon and those without Raynaud's phenomenon. PMID- 2273591 TI - [Evaluation of renal function in chronic renal disease with special reference to creatinine]. AB - Creatinine clearance (Ccr) has been used to evaluate glomerular filtration rate (GFR) in patients with various kinds and grade of renal disease. It is quite useful in terms of simplicity, accuracy and convenience in clinical medicine. However, for the purpose of clinical research, it is not adequate to assess GFR, since a significant quantity of creatinine is secreted in the renal tubule. The secretion rate is rather increased in the endstage chronic renal disease, misleading the true GFR. It also induces an error to calculate the progression rate of a patient with chronic renal failure or to evaluate the effect of the drugs or diet therapy. Therefore, some other indices should be, in future, investigated in order to establish the quantitative evaluation of GFR in patients with chronic renal failure in stead of Ccr or serum creatinine. PMID- 2273592 TI - [Morphological study of renal changes with age: the possibility of kidney donations by the elderly]. AB - Samples from seventy autopsy cases ranging from 27 to 79 years of age who had shown no evidence of renal or malignant diseases were examined histologically to clarify renal changes with age. We evaluated scores for renal histological change and referred the scores to clinical laboratory data; blood pressure, complete blood counts (RBC count, hematocrit, hemoglobin), serum chemistry values (creatinine, urea nitrogen, total cholesterol, total protein, sodium, potassium, chloride) and urinalysis (protein, sediment). We found the score to be related to serum creatinine level, blood urea nitrogen level and the degree of hematuria but not related to the other factors. The progression of arteriosclerosis, tubulo interstitial change and global sclerosis were found to be severe with ageing. Also renal weight decreased with increasing age. However there were great differences among individuals in the extent of changes. We could not assume histological changes were generally severe in those of more than 55-65 years of age. It was impossible to clarify renal states only with clinical findings. Some kidneys had severe histological changes though less than 2.0 mg/dl of serum creatinine level. It suggests that living relatives and cadavers over 60 years old can be donors for renal transplantation when there are no significant findings of abnormality in preoperative evaluations of their physical state. If insufficient examinations are done, we cannot determine which of them will be good donors. Therefore preoperative biopsy is the best way to evaluate donor suitability. To evaluate only clinical data, it is necessary that serum creatinine level be less than 1.2 mg/dl, blood urea nitrogen level be less than 23 mg/dl and there be no hematuria. PMID- 2273593 TI - [Morphological and functional alterations in the intercalated cells of outer medullary collecting duct in K-depleted rats--with special reference to ultrastructural change on electron microscopy]. AB - It has been known that morphological changes are predominant at the site of intercalated cells (IC-cells) of the rat outer medullary collecting duct (OMCD) under K depletion. The changes are characterized by an increase in microplica and the stud of the apical plasma membrane in association with a decrease in the tubulovesicular membrane compartment of the apical region of the cells. It has also been shown that significant K reabsorption and acceleration of H secretion are taking place in these cells of OMCD under the K depletion. In order to clarify whether the changes are directly related to K reabsorption or H secretion, the animal experiment was carried out under any condition. In the control group, G-I, rat was fed with standard diet of normal K content (serum K; 4.5 +/- 0.2 mEq/l), whereas K content was decreased in the K depletion group, G II, (serum K; 2.7 +/- 0.6 mEq/l). In the acid loaded group, G-III, 4 mEq/100 g BW of 2N ammonium chloride was given every day (serum K; 4.0 +/- 0.2 mEq/l). Animals were sacrificed after 14 days and kidneys were removed for morphological and biochemical examinations. As a result, a significant cell proliferation and interstitial PAS positive granules are observed in K-depleted rats under the light microscopic study. Under the electron microscope, the changes of the intracellular ultrastructure are predominant in the IC-cells of OMCD, such as 'membrane recycling'. On the contrary, no particular changes are seen in acid loaded rats under the light microscope.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273594 TI - [Effects of human Cu, Zn-superoxide dismutase in aminonucleoside nephrosis- evaluation of the morphology and glomerular basement membrane anionic charge sites]. AB - It was examined whether superoxide dismutase (SOD) had protective effects in puromycin aminonucleoside nephrosis (PAN). Nephrotic rats were induced by a single intraperitoneal injection of puromycin aminonucleoside (PA, 60 mg/kg). Subcutaneous administration of SOD (30 mg/kg) was started the day before PA injection and continued every 24 hours. Animals were sacrificed 10 days later to assess the morphology and glomerular basement membrane anionic charge sites (CSs). GBM CSs were stained in vitro with polyethyleneimine (PEI) and studied by electron microscopic examination. The SOD-injected group had a significant reduction of urinary protein excretion compared to the PA-treated group. Light microscopy revealed that vast majority of glomeruli in PA-treated group had segmental mesangial expansion and epithelial cell adhesions of the glomerular tuft to Bowman's capsule. Contrasted to these changes in the PA group, glomeruli from SOD-treated group showed less severe morphologic changes. On electron microscopy, the PA-treated rats exhibited marked glomerular epithelial loss of foot processes, epithelial attenuation, cytoplasmic vacuolization and protein reabsorption droplets. The SOD-treated animals demonstrated a lesser degree of epithelial loss of foot processes with a few protein reabsorption droplets. There was also a significant decrease in GBM lamina rara externa CSc stained with PEI in PAN compared to the control. The SOD-treated rats had a significant increase in GBM CSs compared to those of the PAN rats. SOD has protective effects in urinary protein excretion, the morphology and GBM CSc in PAN, which indicate indirect evidence that superoxide and/or its metabolites are responsible for glomerular injury. PMID- 2273595 TI - [Effect of methylprednisolone pulse therapy in patients with lupus nephritis assessed by WHO morphologic classification]. AB - To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group. PMID- 2273596 TI - [The long-term effects of a new converting enzyme inhibitor, delapril hydrochloride, on renal function, renin-angiotensin-aldosterone system and kallikrein-kinin prostaglandin system in hypertensive patients]. AB - The effects of a new angiotensin converting enzyme inhibitor, delapril hydrochloride, (delapril) on renal function, and the renin-angiotensin aldosterone and kallikrein-kinin prostaglandin systems were studied in 10 hypertensive patients. After 4 to 12 months (7.6 +/- 0.9 [SE]) of treatment with 15-60 mg/day (36 +/- 6.8) of delapril (b.i.d.), mean arterial pressure was decreased from 126 +/- 3.0 to 110 +/- 4.4 mmHg (p less than 0.01). Although renal blood flow (RBF), assessed by PAH clearance and hematocrit, was increased from 437 +/- 51 to 490 +/- 49 ml/min (p less than 0.05) and renal vascular resistance was decreased (p less than 0.05), glomerular filtration rate, measured by endogenous creatinine clearance, did not change significantly. Thus, filtration fraction was reduced (p less than 0.01). Plasma renin activity was increased from 1.5 +/- 0.3 to 4.4 +/- 1.1 ng/ml/hr (p less than 0.01). Plasma aldosterone concentration tended to decrease (p less than 0.1), and urinary aldosterone excretion showed on significant change. Although urinary kallikrein and prostaglandin E2 excretions were increased (p less than 0.05), urinary thromboxane B2 excretions was reduced (p less than 0.05). In addition, the changes in RBF were significantly correlated with those in urinary PGE2 excretion (r = 0.63, p less than 0.05). These results suggest that the antihypertensive effect of delapril is multifactorial and that the improvement of RBF seen during delapril administration in the present study may be partly due to the suppression of the renin-angiotensin-aldosterone system and the activation of kallikrein kinin-prostaglandin system. PMID- 2273597 TI - [The clinical value of correction of acidosis by acetate-free biofiltration in patients on regular dialysis treatment]. AB - Effects of metabolic acidosis were compared between bicarbonate dialysis (BCD) and acetate-free biofiltration (AFB). Three stable dialysis patients (1M, 2F, mean age 30 yrs) were selected for the study because their bicarbonate (BC) pre dialysis plasma concentration were always under 16 mmol/l while they were on 33 mmol/l-BCD thrice weekly for 12 months. They were switched to a 6 months period of AFB. Pre- and post-dialysis BC plasma concentration, other blood chemical parameters and mass removal (total collection of used dialysate) of urea (U), creatinine (Cr), uric acid (UA), and phosphate (P) were measured during the last week of each period, including 3 dialysis sessions. Mean calorie and protein intake were 29.4 KCal/kg.d and 1.5 g/Kg.d (BCD period) and 38.2 Kcal/Kg.d and 1.5 g/Kg.d (AFB period) respectively. BC plasma concentration (Mean +/- SE, mmol/l) at the pre and post-dialysis in AFB were significantly higher than those in BCD (16.6 +/- 0.7 vs 20.8 +/- 0.6; p less than 0.001, 22.7 +/- 0.8 vs 25.8 +/- 0.8; P less than 0.02). Pre- and post-dialysis U plasma concentration (Mean +/- SE, mmol/l) in AFB were significantly lower than those in BCD (34.3 +/- 2.51 vs 20.8 +/- 0.59, 10.5 +/- 1.32 vs 7.5 +/- 0.92; P less than 0.001). Pre-dialysis P plasma concentration (Mean +/- SE, mmol/l) in AFB was significantly lower than that in BCD (1.85 +/- 0.09 vs 1.50 +/- 0.15; P less than 0.01). Cr, UA and P mass removal in BCD and AFB were not significantly different. However, U mass removal in AFB was significantly lower than that in BCD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273599 TI - [Paradoxical response of blood pressure to salt loading in renovascular hypertension]. AB - We studied the effect of high salt intake on blood pressure in two cases with renovascular hypertension. They had hypertension with hyperreninemia and marked difference in plasma renin activity between both renal veins. Blood pressure significantly decreased after single oral administration of captopril. Renal arteriogram revealed significant stenosis in the main artery to the left (case 1) and right (case 2) kidney. Blood pressure response was evaluated after seven (case 1) and five (case 2) days of low salt and seven days (both cases) of high salt intake. Mean blood pressure in two patients was significantly decreased (case 1; 118 +/- 5.5 to 108 +/- 6.1 mmHg and case 2; 150 +/- 3.8 to 138 +/- 3.1 mmHg). Plasma renin activity was also decreased (case 1; 6.25 to 0.77 ng/ml/hr and case 2; 22.8 to 6.3 ng/ml/hr). In case 2, blood pressure elevated markedly during low salt intake, compared with blood pressure level during normal salt intake. The results suggest that excessive salt intake in patients with unilateral renovascular hypertension produces blood pressure reduction because of suppression of renin-angiotensin system. We concluded that in patients with unilateral renovascular hypertension dietary sodium depletion may be harmful, whereas salt supplement may have a beneficial effect. PMID- 2273598 TI - [Bucillamine-associated membranous nephropathy in a patient with rheumatoid arthritis]. AB - A case of bucillamine-associated membranous nephropathy in a patient with rheumatoid arthritis was reported. A 34 year-old woman was admitted to our hospital because of proteinuria in September, 1988. Rheumatoid arthritis had been diagnosed in April, 1988, and had been treated with bucillamine (disease modifying anti rheumatic drug) and amfenac (nonsteroidal antiinflammatory drug). The renal biopsy specimens showed Stage I membranous nephropathy, on both electron and immunofluorescence microscopy. Proteinuria decreased after the drugs were withdrawn despite continued RA symptoms. These results were consistent with drug induced nephropathy. Since bucillamine has some resemblances in its structure and pharmacologic action to D-penicillamine, which sometimes induces membranous nephropathy, it is thought that the nephropathy in this case was caused by an adverse reaction to bucillamine. PMID- 2273600 TI - [Acute renal failure in a case of paroxysmal nocturnal hemoglobinuria--a review of literature in Japan]. AB - A case of paroxysmal nocturnal hemoglobinuria (PNH) associated with acute renal failure (ARF) is described. A 57-year-old female, who had been diagnosed as having PNH in 1983 at Kochi Medical School, was admitted to our hospital in April 1989, because of ARF with dark urine after a common cold. Hemodialysis was performed 5 times for ARF, and after almost completely recovering from ARF, she was discharged. The renal biopsy showed the deposition of hemosiderin in the proximal tubular cells. We surveyed fourteen case reports of PNH associated with ARF in Japan including our case. Ten cases developed ARF after infection causing hemolytic attack. Twelve of 14 cases were treated by hemodialysis and 13 cases were reversible. The histopathology of their renal biopsies revealed the deposition of hemosiderin in the proximal tubular cells in six of seven cases and tubular necrosis in three cases. These data showed that hemolytic attack and dehydration related to infection facilitated the induction of ARF. PMID- 2273601 TI - [Adrenal tumors associated with renal cell carcinoma]. AB - We experienced two cases with renal cell carcinoma who showed enlargement of the contralateral adrenal gland. In case 1, the enlarged adrenal gland was a non functioning adrenal adenoma, and in case 2, it was a metastatic adrenal tumor. Non-functioning adrenal adenomas are benign tumors of the adrenal cortex often found incidentally at autopsy or on computed tomography (CT) studies of the upper abdomen. Adrenal adenomas have been reported to occur in 9.5-14% of patients with renal cell carcinoma, while the incidence being 1.5-8.7% in the general population. Since metastases of renal cell carcinoma to the adrenal glands are not uncommon, it is important to distinguish between non-functioning adrenal adenomas and metastatic tumors. Therefore, we studied the incidence of adrenal tumors (including metastatic tumors and benign tumors) in patients with renal cell carcinoma who underwent the abdominal CT study in our hospital. From 1982 to 1989, CT had been performed in 67 patients with renal cell carcinoma. Six adrenal masses were identified with CT in these patients. Three out of the 6 patients probably had metastatic tumors and one of the 3 adrenal masses was pathologically diagnosed as metastatic tumor. The other three masses were benign on pathology and only one of them was pathologically diagnosed as non-functioning adrenal adenoma. The incidence of adrenal adenomas on the CT study was lower than that of previous studies based on autopsy. The reasons of this difference in results between their studies and ours are not clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273602 TI - The development of immunological studies in hepatitis. PMID- 2273603 TI - Clinical evaluation of 12 cases of antimicrobial drug-induced pneumonitis. AB - The diagnosis of drug-induced pneumonitis is generally difficult, and it is made clinically by Tamura's criteria. We experienced 12 cases (7 definite and 5 possible cases) of antimicrobial drug-induced pneumonitis (one of case was the first case caused by carbapenem). Symptoms such as fever (11/12), cough (10/12) and dyspnea (10/12) and laboratory data such as eosinophilia (7/12), elevation of IgE (4/6) and hypoxia (11/12) were commonly seen in these patients, although they were not specific. Lymphocyte stimulation test (5/11) and provocation test (4/8) were quite suggestive of drug allergy. Bronchoscopy has been used for confirmation of pneumonitis. Transbronchial lung biopsy revealed alveolitis (4/9) or alveolar fibrosis (3/9), and bronchoalveolar lavage showed lymphocytosis (6/6) and depression of OKT4/T8 ratio (3/5). The combination of bronchoscopic and immunological examinations were more confirmative for diagnosis. PMID- 2273604 TI - Gallium-67 scanning in patients with malignant pleural mesothelioma. AB - The findings of Gallium-67 scans in eleven patients with malignant pleural mesothelioma were reviewed and compared to those of chest CT findings. All patients had an abnormal thoracic Ga-67 accumulation. Six out of 11 showed a diffuse accumulation over the entire involved hemithorax and a localized uptake was shown in 5. A marked diffuse thickening of pleura in the absence of adequate gallium accumulation was observed in one patient. Two out of 11 had a reduction of gallium uptake after having combination chemotherapy. These results suggest that a diffusely increased uptake over the entire involved hemithorax is the most characteristic finding of Ga-67 scan in malignant pleural mesothelioma, and that Ga-67 scans may be helpful as a valuable indicator of the proper therapy. However, the superiority of Ga-67 scan to thoracic CT as a means of determining the extent of disease process could not be verified. PMID- 2273605 TI - Prevalence of dementia in a Japanese community (Hisayama): morphological reappraisal of the type of dementia. AB - The prevalence of dementia was studied in 887 males and females Hisayama residents aged 65 or over (screening rate, 94.6%) using clinical information, neurological examination and dementia scales. We found 59 cases with dementia, the prevalence being in 6.7% of the screened population with females predominant. Vascular dementia was more frequent, with the ratio of vascular dementia to senile dementia of Alzheimer's type being 4.5 for males and 1.2 for females. Brain-pathology in 47 cases with dementia out of 59 was examined by CT scan or at autopsy during the subsequent 20-month period. Based on the morphologic diagnoses, vascular dementia was high in frequency at 55% of the demented cases, being three times higher than senile dementia of Alzheimer's type. PMID- 2273606 TI - Clinical studies on amyloidosis complicated with rheumatoid arthritis--with particular reference to nephropathy. AB - Twenty-two patients with definite or classical rheumatoid arthritis (RA) who were diagnosed as amyloidosis by biopsy or at autopsy were investigated. The average duration of RA prior to the diagnosis of amyloidosis was 16.5 +/- 12.5 years. The symptoms that led to the diagnosis of amyloidosis were renal symptoms in 11 cases and gastrointestinal symptoms in 5 cases. Urinary protein was positive in 16 cases (73%). The degree of proteinuria varied in each case. Nephrotic syndrome was observed in 5 cases. Azotemia (Cr greater than 1.5 mg/dl) was present in 18 cases (82%). The period from the diagnosis of amyloidosis to death was 3.0 +/- 2.2 years. The causes of death were uremia in 10 cases, heart failure in 2 cases, malignancy in 2 cases, sepsis in 2 cases and others in 2 cases. Thirteen patients were autopsied and the frequency of amyloidosis complicated with RA was 22.0% in autopsied rheumatoid patients. Although nephropathy was present in most cases of amyloidosis complicated with RA, proteinuria and azotemia greatly varied in both degree and course. PMID- 2273607 TI - Reversible ischemic cerebrovascular disease associated with hyperleukocytosis in a patient with chronic myelogenous leukemia. AB - A 31-year-old man with chronic myelogenous leukemia in a chronic phase complicated with reversible ischemic cerebrovascular disease is described. Before therapy, the WBC count was 530.0 x 10(9)/l. Four days after initiation of busulfan, he rapidly developed disturbance of consciousness and right hemiplegia. Computerized tomography demonstrated the presence of multiple low density areas in the cerebrum. The symptoms were, however, completely relieved in accordance with the decrease in the WBC counts in 8 days. Repeated CT studies showed no abnormal findings after one month. The intracranial change was considered to be one of the manifestations of hyperleukocytic syndrome. PMID- 2273608 TI - Asymptomatic hereditary xanthinuria: a case report. AB - A 22-year-old man with hereditary xanthinuria is reported. A biochemical study of the patient showed elevated serum levels of xanthine and hypoxanthine with concomitant increases in urinary excretion of xanthine and hypoxanthine. The xanthine oxidase activity in the duodenal mucosa of the patient was about 1.5% of normal value. Urinary excretion of xanthine and hypoxanthine of his parents and his eldest brother were significantly higher than the corresponding normal values, but the values were much less than those of the patient. The results suggested that the patient was homozygote, and his parents and his eldest brother were heterozygotes. PMID- 2273609 TI - Recurrence of anti-glomerular basement membrane antibody glomerulonephritis. AB - Recurrence of anti-glomerular membrane antibody glomerulonephritis seems to be an unusual clinical phenomenon. We report a 57-year-old man with recurrence of anti glomerular basement membrane antibody glomerulonephritis. He developed a rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody (anti-GBM Ab), and recovered with a combined treatment of prednisolone, anticoagulant and antiplatelet agents. After a 2-year remission, hematuria and proteinuria followed by renal functional deterioration occurred without any obvious cause. The second renal biopsy revealed cellular crescents with linear IgG deposition along GBM, a finding similar to the first one. The aforementioned combined treatment resulted in a gradual recovery from proteinuria and renal functional derangement. PMID- 2273610 TI - Milk of calcium renal stone in a patient with acute promyelocytic leukemia. AB - A case of milk of calcium renal stone is reported. This is a rare disease in which a suspension of calcium salts is formed within a renal cyst. The pathognomonic sign is a fluid level seen in a standing position and an oval density seen in a supine position. In the present case, the milk of calcium was found to develop in a hydronephrotic kidney during the course of acute promyelocytic leukemia and this condition was suggested to be a complication of infection. PMID- 2273611 TI - A case of amnestic syndrome due to right thalamic infarction. AB - A 66-year-old right-handed woman with amnestic syndrome due to right thalamic infarction, is described. Amnestic syndrome in this case was both anterograde verbal and non-verbal (visuospatial) memory impairment in the acute stage and only non-verbal impairment in the chronic stage. On the basis of these observations and previous reports, it was concluded that her memory impairment may be the result of cortical hypometabolism following thalamic infarction. PMID- 2273612 TI - Rapidly progressive deteriorated left ventricular wall motion associated with tetanus: a case report. AB - A case of tetanus accompanied by severe reversible left ventricular motion impairment is reported. Emergent coronary angiography showed no abnormalities and large akinesis was present on left ventriculography. The plasma catecholamine level was not too high in the acute phase, therefore it is thought that the cause of this depressed left ventricular wall motion abnormality was due to some metabolite derived from tetanus. PMID- 2273613 TI - A successfully treated case of Vibrio vulnificus septicemia with shock. AB - Vibrio vulnificus infection often causes serious or fatal disease. Recently, in Japan there have been numerous reports of Vibrio vulnificus infection. Here, we report a successfully treated case of Vibrio vulnificus septicemia with shock, disseminated intravascular coagulation (DIC) and necrotizing cellulitis in a middle-aged heavy drinker with chronic alcoholic liver disease. On reviewing 38 cases in Japan including ours, the overall mortality rate was 68%. Although the incidence is relatively low, it is recommended to warn patients in the high risk category, such as liver disease patients, to avoid raw fish and shellfish and limit sea water exposure. PMID- 2273614 TI - A case of cardiac injury and acute renal failure induced by electrical burn. AB - Reported is a case of electrical burn associated with cardiac injury and acute renal failure in a 21-year-old man. After coming into contact with a high-tension cable, he became drowsy and oliguria developed. Twenty-four hemodialyses were required. Although the ECG findings revealed an inferior wall myocardial infarction, neither cardiac scintigram (201TlCl) nor ultrasonic cardiography revealed any local lesions. In this case the cardiac damage following electrical burn appeared different from true myocardial infarction. PMID- 2273615 TI - Lactic acidosis with hypoglycemia and hyperammonemia observed in two uremic patients during calcium hopantenate treatment. AB - Calcium hopantenate (HOPA), a drug for treating symptoms of cerebrovascular disease, is a derivative of gamma-amino butyric acid and is also an analog of pantothenic acid. It is speculated that calcium hopantenate may affect lactate generation, glucose metabolism, and ammonia disposal through the inhibition of pantothenic acid metabolism. We report two uremic patients with complaints of consciousness disturbance with lactic acidosis, hypoglycemia and hyperammonemia. HOPA is mainly excreted with urine. Severe accumulation of HOPA, documented at the onset of unconsciousness in our uremic cases, might be responsible for marked inhibition of pantothenic acid metabolism. PMID- 2273616 TI - Basophilic crisis in chronic myelogenous leukemia: case report and literature review in Japan. AB - A 37-year-old female with Ph1-positive chronic myelogenous leukemia developed basophilic crisis 11 months after diagnosis of the disease. Splenomegaly was absent throughout most of the course. The survival duration from the blastic crisis was 5.5 months. Eleven cases in Japanese literature are reviewed. PMID- 2273617 TI - Anti-atherogenic action of eicosapentaenoic acid. PMID- 2273618 TI - Gastric mucosal hexosamine contents in patients with renal diseases. AB - Since gastric mucosal lesions are frequently encountered in patients with renal disease, we measured the gastric mucosal hexosamine (Hx) content in 51 patients with renal disease. Endoscopic examination revealed that nearly half of the patients had erosive gastritis, and that duodenal ulcers (Dus) were more common than gastric ulcers (Gus). The gastroduodenal lesions were increased in patients with advanced renal dysfunction. The relationship between Hx content and various indicators of renal function, including creatinine clearance (Ccr), serum creatinine (cr), blood urea nitrogen (BUN), and 24-h urine protein excretion, were also evaluated. The Hx content decreased in the early stage of renal dysfunction. However, it returned to normal to near normal levels in advanced renal disease and patients who underwent hemodialysis. Since the Hx content was decreased in the early stage of renal dysfunction, careful follow-up appears to be necessary in patients with renal disease. PMID- 2273619 TI - The efficacy of interferon-alpha treatment in human T-lymphotropic virus type-I associated myelopathy. AB - We investigated the efficacy of interferon-alpha (IFN-alpha) treatment in 5 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). Treatment with IFN-alpha yielded clinical improvement of gait, and sensory and/or sphincter disturbance in 4 out of the 5 HAM patients. IFN-alpha treatment did not bring about uniform changes in lymphocyte subsets or anti-HTLV-I antibody titer of peripheral blood. Although the stimulation indexes to phytohemagglutinin, concanavalin A, and pokeweed mitogen were decreased in the culture of the peripheral blood lymphocytes (PBL) in the 5 HAM patients before the treatment, the stimulation indexes to these mitogens were significantly increased except in 1 case after the IFN-alpha treatment. These changes were based primarily on the depression of the spontaneous proliferation of PBL without mitogen. These results appear to point out a very important phenomenon for the investigation of the pathogenesis of HAM. PMID- 2273620 TI - An analysis of hypermagnesemia and hypomagnesemia. AB - Serum magnesium (Mg) was measured in 6,252 patients; in 1,246 (19.9%) the value was abnormal. Hypermagnesemia (serum Mg greater than or equal to 3.9 mg/dl) was observed in 51 patients (0.8%) and hypomagnesemia (Mg less than or equal to 1.5 mg/dl) in 165 (2.6%). Hypermagnesemia was found in patients with renal failure treated with Mg-containing antacids or cathartics, or with eclamptic convulsions treated with Mg sulfate. The most frequent clinical finding of hypermagnesemia was urinary disturbance, although various other neurological signs and symptoms were observed. Hypomagnesemia was seen in patients with various diseases such as cancer, hepatic cirrhosis, cerebrovascular disease, and generally poor condition. Abnormalities of electrolytes other than Mg were also frequently observed. The most common clinical findings of hypomagnesemia were personality changes and depression. The differentiation from psychiatric disease is important. PMID- 2273621 TI - A unique variant of hairy cell leukemia in Japan. AB - We studied 25 Japanese patients with hairy cell leukemia (HCL) and found a manner in which HCL can be divided into two subtypes. In each patient, hairy cells (HC) showed striking surface hairs and reacted with HC-specific antibodies (alpha Leu M5 and alpha HC-M). Twenty of the 25 patients had HC characterized by round nuclei with dense nuclear chromatin, weak tartrate-resistant acid phosphatase (TRAP) activity and the phenotype of low density surface immunoglobulin (SIg)+, Tac-. In this group of 20 patients, the male to female ratio was low, and there was frequent leukocytosis. On the other hand, the remaining 5 patients showed a high male to female ratio and a normal or decreased leukocyte count. HC had folded nuclei, strong TRAP activity and the phenotype of high density SIg+, Tac+. The features of the latter patients are consistent with those of HCL in Western countries, while those of the former group appear to indicate a unique variant of HCL. PMID- 2273622 TI - Combination of ambulatory electrocardiographic monitoring and psychological testing in coronary artery disease patients. AB - Ambulatory electrocardiographic monitoring and psychological testing were performed in 100 patients with chronic stable myocardial infarction. These patients were divided into four groups according to their chest pain and transient ST-segment depression by Holter monitoring during the follow-up period: group A, 40 patients without complications; group B, 20 patients with silent myocardial ischemia; group C, 14 patients with episodes of chest pain alone; and group D, 26 patients with postinfarction angina. Whereas group B had silent myocardial ischemia and extroversion, groups C and D were characterized by introversion and neuroticism. The frequency of multi-vessel disease was 41% for group A, 53% for group B, 8% for group C and 70% for group D. The patients of group B not only received treatment for coronary artery disease but also behavioral counseling and those of group C received psychotherapy. The results support the view that a combination of Holter monitoring and psychological testing is clinically useful for the development of therapeutic strategies for coronary artery disease. PMID- 2273623 TI - Guillain Barre syndrome following herpes zoster: a case report and review of literature. AB - Herpes zoster is known to exhibit various neurological complications. Guillain Barre syndrome following herpes zoster is rare and only 25 cases have been reported to date. In this report, a case is presented and the pertinent literature is reviewed. PMID- 2273624 TI - Successful pregnancy and delivery in a patient with neurogenic orthostatic hypotension and achalasia: a case report. AB - A successful pregnancy and delivery in a patient with neurogenic orthostatic hypotension and a past medical history of achalasia is described. Surprisingly, she was free from orthostatic hypotension during the last trimester, though the evaluation of adrenergic function by measurements of changes in plasma norepinephrine on standing and by the response of blood pressure to infused norepinephrine revealed no difference between function before pregnancy and that during the last trimester. Orthostatic hypotension started again just after delivery. PMID- 2273625 TI - Effect of cyclophosphamide pulse therapy in a patient with intractable lupus nephritis. AB - A 32-year-old female was suffering from intractable lupus nephritis (LN). Prednisolone at 30 mg per day had been prescribed for two months because of massive proteinuria and edema. After that, anasarca and orthopnea were induced, and hypoproteinemia, hypercholesteremia, and anti-cardiolipin antibody were observed. Prednisolone at a dose of 60 mg per day was necessary. However, there was no improvement of the nephrotic state and renal pathological changes shown as diffuse proliferative lupus nephritis were followed by moderate crescent formation as determined by serial needle biopsy. Cyclophosphamide (CYP) pulse therapy was started and marked improvement of LN was obtained clinically and serologically without significant adverse effects. PMID- 2273626 TI - Danazol treatment for paroxysmal nocturnal hemoglobinuria. AB - Danazol was administered to two patients with paroxysmal nocturnal hemoglobinuria (PNH) with a dramatic effect on the hematological findings. The patients, 31- and 41-year-old females, were initially diagnosed as having aplastic anemia, and were initially treated with anabolic steroid and immunosuppressive therapy, respectively. Sugar water and Ham tests turned positive at the start of danazol therapy in the former patient and after two months in the latter patient. This drug produced a dramatic improvement in the hemoglobin level and the platelet count and showed few side effects in the patients. A possible mechanism of action of danazol for PNH is briefly discussed. PMID- 2273627 TI - Cerebral hemiatrophy in systemic lupus erythematosus: report of a case. AB - An 18-year-old woman with systemic lupus erythematosus developed neuropsychiatric disorders, including aseptic meningoencephalitis, organic brain syndrome and seizure. A series of computed axial tomography scans revealed the progression of marked atrophy of the right cerebral hemisphere for a period of 3 years without occlusion or stenosis of large vessels on cerebral angiography. I-123 IMP single photon emission computed tomography disclosed a markedly decreased uptake of I 123 IMP in the right cerebral hemisphere, and also in the left cerebellar hemisphere (crossed cerebellar diaschisis), which disappeared within 2 years. PMID- 2273628 TI - A case of primary aldosteronism with renovascular hypertension. AB - A case of primary aldosteronism associated with renovascular hypertension is reported. The patient, a 46-year-old woman, developed hypertension to the level of 210/110 mmHg. Laboratory data included serum potassium 3.4mEq/l, plasma renin activity 25ng/ml/h and plasma concentration of aldosterone 330 pg/ml. Occlusion of the left renal artery and left adrenal aldosteronoma was diagnosed by radiographic and hormone analysis findings. Left adrenalectomy and nephrectomy corrected the hypertension. The possibility of tertiary aldosteronism is discussed. PMID- 2273629 TI - Pseudocoarctation of the aorta--a case report. AB - We report a case of a 43-year-old woman with pseudocoarctation of the aorta manifested by a superior mediastinal mass on the chest roentgenogram. Evaluation was made using computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). No other congenital anomalies or aneurysms below the kinked area of the aorta could be found. The characteristic "kink" of the aorta and the absence of true coarctation were evident in the sagittal plane by MRI. MRI is of great value for examining disorders of the aorta. PMID- 2273630 TI - Disseminated mycobacterial infection in a hemophilia B patient with acquired immunodeficiency syndrome. AB - Disseminated mycobacterial infection was found at autopsy in a male patient with hemophilia B and acquired immunodeficiency syndrome (AIDS). In May 1986, 23 months before death, the patient had encephalitis for one month and in July he developed a fever, malaise and generalized lymphoadenopathy. Human immunosuppressive virus (HIV) was positive and the CD 4/8 ratio of lymphocyte surface markers was 0.1, but mycobacterium was not detected. In September 1986, he had severe dyspnea due to interstitial pneumonia and he was treated with high dose methylprednisolone. He died after a 23-month course of fever, severe weight loss and terminal progressive deterioration, although he was treated with antibiotics, antifungal agents, gamma-globulin, steroid and a Azidothymidine. PMID- 2273631 TI - An autopsy case of hypertrophic cardiomyopathy showing dilated cardiomyopathy like features by serial ventriculography. AB - An autopsy case of hypertrophic obstructive cardiomyopathy (HOCM), in which the clinical features of dilated cardiomyopathy (DCM) developed after 10 years is described. Three serial left ventriculograms (LVG) and bi-ventriculograms (BVG) were performed during the 10-year follow-up. At the time of the first observation, the ECG revealed a giant negative T wave (GNT) in V5 (-1.5mV) and high voltage (SV1 + RV5 = 8.1mV). The LVG and BVG showed concentric left ventricular wall hypertrophy and a pressure gradient in the left ventricular out flow tract. However, follow-up studies disclosed resolution of the GNT with decreased high voltage. All wall thicknesses and the ejection fraction were significantly decreased and the wall motion was reduced serially. These findings were consistent with the clinical profile of DCM. At autopsy, the heart weighed 610 g and showed dilated change of the left ventricular cavity. Significant myocardial fibrosis, bizarre myocardial hypertrophy with disorganization (BMHD) and severe narrowing of the intramural small arteries due to intimal thickening were found in the left ventricular wall, especially in the anterior and interventricular septal wall. This autopsy case suggests that some cases of HCM, with serial disappearance of the deep negative T wave and high voltage, deteriorate to the clinical profile of DCM. PMID- 2273632 TI - Malignant lymphoma of the lung: report of an autopsy case and review of literature. AB - A 74-year-old man complained of a cough and left chest pain. Chest X-ray showed marked pleural effusion and a large mass in the left lower lobe, and air bronchograms within the mass were observed by tomography and computed tomography (CT). About 3 months later, the patient died of left atelectasis and pneumonia. Autopsy revealed a localized tumor in the lower lobe of the left lung. Histologically, proliferation of lymphoma cells was noted. Immunoglobulin staining showed B cell-type monoclonality. No metastasis was evident except for a very small nodular area in the left renal cortex. PMID- 2273633 TI - Molecular mechanisms of reception and transduction in olfaction and taste. PMID- 2273634 TI - Dependence of contractile responses by some calcium antagonists on external calcium in the skeletal muscle. AB - Dependence of contractile potentiation by calcium antagonists on external calcium was investigated on the frog's twitch muscle. Low concentrations (10(-6) to 10( 5) M) of nicardipine and verapamil enhanced the peak tension of both twitch and electrically induced contracture in the presence of calcium. In the calcium-free media the drugs suppressed the contractile tension. Caffeine contracture was inhibited by the calcium antagonists at 20 degrees C. This inhibition was caused by an early onset of relaxation, which was not observed at 7 degrees C. The results suggest that some interaction between calcium ions and drug molecules at the voltage sensor on the transverse tubular membrane, which regulates E-C coupling but is not directly related to the functional calcium channel, may play an important role for the phenomena. The inhibitory action of calcium antagonists on the caffeine contracture in the presence of calcium is probably independent of the potentiating effect seen in the depolarization-induced contractions. PMID- 2273635 TI - Effect of potassium solution on rehydration in rats: comparison with sodium solution and water. AB - Thermally dehydrated rats were given isotonic KCl, NaCl solution, or tap water ad libitum for 17 h and the differences of the restoration rate in fluid and cation were compared between the groups to elucidate the effect of Na+ and K+ ions on the replacement of each body fluid compartment during rehydration. When rats were provided with NaCl solution, the gains of fluid and Na+ exceeded the amounts lost during the dehydration period, while in the isotonic KCl and tap water groups fluid gain was 70% of the fluid lost during the dehydration period. The recovery of extracellular fluid (ECF) volume was 178% of the loss in the NaCl group and 50% in the KCl group. The Na+ concentration of the ECF was regulated closely in all groups. The recovery in intracellular fluid (ICF) volume did not differ significantly between groups and never exceeded the control level, but tended to be higher in the KCl group than in the NaCl group. These results indicated that in the ECF the regulation of Na+ concentration preceded that of volume while in the ICF, volume regulation had priority. In addition, the effect of K+ supplementation on the recovery of ICF volume after thermal dehydration was shown to be modest, unlike the effect of Na+ on the recovery of ECF volume. PMID- 2273636 TI - Necessity of hyperglycemia for effects of endogenous cholecystokinin on insulin and pancreatic exocrine secretion in conscious rats. AB - The effects of endogenous cholecystokinin (CCK) on insulin and pancreatic exocrine secretion were examined in conscious rats. Rats with bile and pancreatic fistulae, one duodenal cannula, and two jugular vein cannulae were divided into four groups, with and without glucose infusion (0.2 g/(ml.h)), and with bile and pancreatic juice (BPJ) diversion and return. Without glucose infusion, BPJ diversion did not have any significant effect on the plasma level of insulin or glucose; but with glucose infusion, it caused a significant increase in plasma insulin concentration 1 h after the diversion. The plasma glucose concentrations in the groups with BPJ diversion and return were not significantly different, and the response of pancreatic exocrine secretion to BPJ diversion was suppressed slightly, but not significantly, by glucose infusion. The plasma CCK concentration was increased significantly by BPJ diversion, but not affected by glucose infusion. These results indicate that, as observed in in vitro experiments with exogenous CCK, in conscious rats, endogenous CCK stimulates both exocrine and endocrine secretion of the pancreas, and that hyperglycemia is necessary for these effects to become apparent. PMID- 2273637 TI - Effects of chelated sera and alteration in calcium concentration on the growth of oral epithelial cells in primary culture. AB - The purpose of this study were to examine the distribution of growth-promoting activity of some chelated sera and to investigate the relationship between calcium concentration in culture medium and the growth-promoting activity of the chelated sera in comparison with that of the original serum. Results showed that the chelated serum obtained by acidic resin treatment promoted colony formation, while the number of colonies decreased in cultures containing either dialyzed serum or chelated one obtained by treatment with alkaline resin. The acid chelated serum and its lyophilized materials maintained the growth-promoting activity for 6 months or more in a deep freezer. This activity depended on the calcium concentration of culture medium in the range from 0.06 to approximately 1.5 mM. The optimal concentration of this material for growth promotion was 4 mg/ml as the protein density, which was about a quarter of that for the original serum protein. Sera from different sources treated with the acidic resin also showed similar effect on the growth. This finding strongly suggests that the acid chelated serum and its lyophilized protein contain a keratinocyte growth factor(s). PMID- 2273638 TI - Ca2(+)-insensitive contraction in glycerinated skeletal muscle fiber treated with additional troponin T. AB - An investigation was carried out on the effect of troponin T (TnT) protein on the Ca2(+)-sensitivity of fiber contraction when it was added to glycerinated muscle fiber. The TnT-treated fiber was observed to lose its Ca2(+)-sensitivity, so that it was seen to contract even in a Ca2(+)-free buffer solution. However, the treated fibers were not significantly different from the normally glycerinated ones in terms of tension magnitude. On the other hand, the fiber did not lose its Ca2(+)-sensitivity upon treatment in a similar manner with troponin I (TnI) or troponin C (TnC) protein instead of TnT; the tension magnitude was seen to decrease only with the TnI treatment. SDS-PAGE patterns of the TnT-treated fibers were different from those of glycerinated ones at the TnI and TnC band, which were fainter in the TnT-treated fibers than in the normal ones. DACM-labeled fibers also decreased in the DACM-labeled TnI and TnC proteins on gel as a result of the treatment with TnT protein. Further, those proteins were completely removed from fibers into extra medium. These findings suggest either that the additional TnT protein removes TnI and TnC subunits from the troponin (Tn) complex combined with thin filaments in the fibers, or that it exchanges the total Tn complex on the thin filaments. PMID- 2273639 TI - A further study on the membrane currents related to Ba-induced pacemaker in the bullfrog atrium. AB - In the SR-poor frog atrial muscle, the presence of transient inward current (ITI) was demonstrated in Ba (0.2-0.3 mM) Ringer after treatment with isoproterenol. A peculiar slow inward current (IU) superposing on the tail of the delayed outward current (IX) was also elucidated at the maximum diastolic potential level, which may enhance the pacemaker depolarization. PMID- 2273640 TI - Effects of acute hypoxia on ventilatory response at the onset of submaximal exercise. AB - In order to investigate the effects of acute hypoxia and accompanying hypocapnia on the ventilatory response at the onset of dynamic exercise, four healthy adult men performed 50W rectangular loads on a cycle-ergometer in normoxic (FIO2 = 0.21) and hypoxic (FIO2 = 0.11) conditions. No statistically significant differences in the initial ventilatory responses to exercise (both delta VI and delta VE assessed on a breath-by-breath basis) were found between eucapnic normoxia (PETO2 approximately 95, PETCO2 approximately 42 Torr) and hypocapnic hypoxia (PETO2 approximately 45, PETCO2 approximately 35 Torr). The present findings support the contention that the neurogenic ventilatory drive at the onset of early exercise is independent from PO2 and PCO2. PMID- 2273641 TI - Effect of barium ions on excitation-contraction coupling of frog twitch muscle fibres. AB - The mechanism for the Ba2(+)-induced potentiation of the twitch tension in frog skeletal muscle was investigated. No significant difference in the peak amplitude of the calcium transients evoked by voltage-clamp depolarizing pulse was found between the fibres bathed in Ca2+ (control) and Ba2+ Ringer's solution, whereas the calcium transients evoked by the action potentials from the fibres in Ba2+ Ringer's solution were increased by about 64%, compared with control. In comparison with control, the action potentials of the fibres in Ba2+ Ringer's solution had a similar overshoot but a significantly longer time course. Our results suggest that excitation-contraction coupling in frog twitch muscle fibres is not altered by replacing Ca2+ with Ba2+. The Ba2(+)-induced potentiation of contraction may be accounted for by broadening of the action potentials. PMID- 2273642 TI - Variation of ascorbic acid content in the different tissues of the frog Rana tigrina as a function of season. AB - Ascorbic acid concentrations of the liver, thigh, and cardiac muscles, ventral and dorsal skin, as well as muscles of the frog Rana tigrina were higher during summer and lower in winter. Ascorbate concentration also showed another high peak in February. The cardiac ascorbate showed minimal seasonal fluctuations. PMID- 2273643 TI - Hemodynamic changes following long-term administration of CS-905, a novel dihydropyridine calcium blocker, in conscious SHR. AB - To investigate the central and regional hemodynamics after long-term administration of CS-905, a novel calcium blocker, we administered the agent (1 and 3 mg/kg/day) for 15 weeks in spontaneously hypertensive rats. At the end of the dosing period, hemodynamic changes were examined using the radioactive microsphere technique. CS-905 produced a sustained dose-dependent antihypertensive effect without inducing tolerance during the 15-week dosing period and prevented cardiac hypertrophy. The agent increased cardiac output, decreased blood pressure and thus decreased total peripheral resistance in a dose related manner. Regional blood flows measured by the microsphere technique were increased in the kidney and brain despite the lowered blood pressure. There was no organ where regional blood flow was decreased. These changes after chronic treatment with CS-905 would be beneficial in the long-term therapy of hypertension. PMID- 2273645 TI - Effects of KT-362, a new calcium release blocker, on vascular selectivity and hemodynamic actions in anesthetized dogs. AB - Pharmacological properties of 5-(3-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-1- oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a newly synthesized calcium release blocker, were studied by comparing its vascular selectivity and cardiovascular actions with those of verapamil, a calcium entry blocker. The relaxing effect of KT-362 in rabbit femoral and basilar artery strips contracted with norepinephrine was greater than that in aortic and coronary artery strips. In anesthetized mongrel dogs, KT-362 (0.1-3.0 mg/kg, i.v.) decreased the mean blood pressure, heart rate and total peripheral resistance in a dose-dependent manner, while cardiac output increased slightly despite a decrease in left ventricular pressure. This is consistent with the data on verapamil. Both i.a. and i.v. injections of KT-362 produced a marked dose dependent increase in vertebral and femoral blood flow. Pretreatment of atropine, propranolol or diphenhydramine exerted no significant effect on the KT-362 induced vasodilation. Verapamil caused a marked increase in the vertebral and coronary blood flows after the injections, but only a slight increase in femoral blood flow. KT-362 at the dose of 10 mg/kg, i.v., had no significant effect on the PQ interval on the electrocardiogram in anesthetized dogs, but 0.1 mg/kg of verapamil increased this interval significantly. These results suggest that KT 362 has properties similar to calcium entry blockers such as verapamil on systemic hemodynamic actions except for the reactivity of vasculatures. PMID- 2273644 TI - Immunohistochemical localization and physiological regulation of carbonyl reductase in immature rat ovary. AB - The present study was performed to clarify the role of the ovarian carbonyl reductase (OCR) in ovarian function in immature rats. The OCR activities towards three specific substrates, 13,14-dihydro-PGF2 alpha, 4-benzoylpyridine and menadione, were photometrically and radiochemically determined in the 9,000 x g supernatants of ovaries, and OCR content was measured by Western-blot-peroxidase anti-peroxidase (PAP) analysis. Immunohistochemical localization of the enzyme in the ovary was performed by the avidin-biotin-complex (ABC) method for paraffin sections. Positive immunoreactivity with OCR antibody was observed for the theca cells and interstitial gland cells at 72 hr after pregnant mare serum gonadotropin (PMSG) treatment when ovulation was confirmed, and the granulosa cells were consistently negatively stained. The OCR activity was significantly increased by PMSG, human chorionic gonadotropin (hCG) and PMSG-hCG treatments, but estradiol and tamoxifen overcame the effect of PMSG on the enzyme activity. Moreover, estradiol enhanced the effect of hCG, but tamoxifen did not. Changes in the OCR activity well-correlated with those in the OCR content. These findings indicate that the OCR is regulated by gonadotropin and estrogen and that metabolites formed by the enzyme could be closely involved in ovarian cell function. PMID- 2273646 TI - Protective effect of DM-9384, a novel pyrrolidone derivative, against experimental cerebral anoxia. AB - The protective effects of DM-9384 [N-(2,6-dimethylphenyl)-2-(2-oxo- 1 pyrrolidinyl) acetamide] against cerebral anoxia were investigated using various animal models. Oral administration of DM-9384 resulted in a significant prolongation of survival time in mice and rats subjected to the normobaric hypoxia; its minimal effective doses were 30 and 10 mg/kg, respectively. A significant protection by this drug against hypobaric hypoxia, histotoxic anoxia and cerebral ischemia also occurred in mice at a dose of 100 mg/kg, p.o. Bifemelane (100-300 mg/kg, p.o.) was protective against these models except for hypobaric hypoxia, and the effects of piracetam, aniracetam and pramiracetam (1000 mg/kg, p.o.) were variable depending on the type of anoxia model used. DM 9384 (100 mg/kg and lower) attenuated the hypolocomotion and the disturbance of cerebral energy metabolism such as a decrease in ATP, an increase in lactate and lactate/pyruvate ratio induced by hypoxia in rats. The spontaneous motor activity, uptake and utilization of brain glucose in normal animals, however, were not influenced by this drug. Based on these results, DM-9384 is characterized as a broad spectrum anti-anoxic drug with negligible CNS depression, and the cerebral protective effect of this drug may be, at least in part, attributable to its ability to improve the cerebral energy metabolic disturbance. PMID- 2273647 TI - A comparison of neurotrophic effects of epidermal growth factor and basic fibroblast growth factor in primary cultured neurons from various regions of fetal rat brain. AB - Effects of recombinant human epidermal growth factor (hEGF) on survival of primary cultured neurons from various regions of fetal rat brain were compared with those of recombinant human basic fibroblast growth factor (hbFGF). Addition of hEGF (0.001-10 ng/ml) in chemically-defined serum-free medium enhanced significantly the survival of cultured neurons from all regions tested, i.e., cerebral cortex, septum, striatum, hippocampus, thalamus, colliculus and cerebellum. However, its effective concentration differed considerably with the regions. The most sensitive regions were the colliculus and cerebellum (minimum effective concentration, 0.001 ng/ml), while the least sensitive was the cerebral cortex (minimum effective concentration, 10 ng/ml). Maximum numbers of surviving neurons in the presence of hEGF were smaller than those of hbFGF in all regions. Maximum effects of hEGF compared with those of hbFGF was greatest in the striatum and smallest in the cerebral cortex. These results suggest that hEGF may exert neurotrophic effects for limited populations of brain neurons. When hEGF (1-10 ng/ml) and hbFGF (0.01-10 ng/ml) were added together, hEGF increased the effects of a lower concentration of hbFGF in an additive manner, but the maximum effects of hbFGF were not potentiated by hEGF in all regions tested. Therefore, mechanisms underlying the effects of hEGF very probably overlap with those of hbFGF. PMID- 2273648 TI - WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task. AB - Using a repeated acquisition procedure in a 3-panel runway apparatus, the effect of WEB 1881 FU on impairment of working memory produced either by scopolamine or by cerebral ischemia was investigated in rats and compared with those of aniracetam and Ca hopantenate. Intraperitoneal injection of scopolamine at 0.56 mg/kg significantly increased the number of errors (pushes made on the two incorrect panels of the three panel-gates located at each choice point). WEB 1881 FU at 10-32 mg/kg, p.o., caused a dose-related reduction in the increase of errors expected in the scopolamine-treated rats. Aniracetam at 10-100 mg/kg, p.o., or Ca hopantenate at 100 and 560 mg/kg, p.o., also significantly diminished the increase in errors induced by 0.56 mg/kg of scopolamine. Cerebral ischemia for 5 min significantly increased errors in the 3-panel runway task. WEB 1881 FU at 32 and 56 mg/kg, administered p.o. immediately after blood flow recirculation and again 1 hr before the runway test, conducted 24 hr after ischemia, significantly reduced the increase in errors expected to occur after 5 min of ischemia. Aniracetam at 32 and 100 mg/kg, p.o., similarly diminished the increase in errors in ischemic rats. These findings suggest that WEB 1881 FU has a beneficial effect on memory that has been impaired by scopolamine or by cerebral ischemia. PMID- 2273649 TI - Effects of repeated administration of pentazocine on ambulatory activity in mice: comparison with the effects of morphine and methamphetamine. AB - Effects of single and repeated administration of pentazocine (5 times at intervals of 3-4 days) were compared with those of morphine and methamphetamine by means of ambulatory activity in mice. The interactions among these 3 drugs were also investigated. Pentazocine (25 mg/kg, s.c.), morphine (10 and 20 mg/kg, s.c.) and methamphetamine (2 mg/kg, s.c.) significantly increased the activity, and the effect progressively enhanced (defined here as development of reverse tolerance) during the repeated administration schedule. The induction of reverse tolerance to pentazocine was less dependent on the environmental conditions, and it was abolished within 2 months. A cross reverse tolerance was demonstrated from methamphetamine to pentazocine and to morphine, and from morphine to pentazocine. However, no significant cross reverse tolerance was induced from pentazocine to morphine and to methamphetamine, and from morphine to methamphetamine. The present results suggest that pentazocine possesses an ambulation-increasing effect, although the characteristics are different from that of either morphine or methamphetamine. PMID- 2273650 TI - Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice. AB - Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect. PMID- 2273651 TI - Effect of omeprazole on delayed healing of acetic acid-induced gastric ulcers in rats. AB - Omeprazole, a gastric mucosal proton pump inhibitor, significantly and dose dependently prevented the delayed healing of acetic acid-induced gastric ulcers in response to repeatedly administered indomethacin to rats. Both basal and histamine-stimulated gastric acid secretions in rats with acetic acid-induced ulcers that were given indomethacin were markedly and persistently (greater than 24 hr) inhibited after 4 weeks treatment with omeprazole. The prevention of delayed ulcer healing by omeprazole appears to be due to its long-lasting antisecretory activity. PMID- 2273652 TI - Vasoactive intestinal polypeptide (VIP) stimulates fibrinolytic system in the rat. AB - We have studied the fibrinolytic effect of VIP in rats. Intravenous injection of VIP enhanced blood fibrinolytic activity in a dose-related manner. The euglobulin fraction obtained from intact rat plasma incubated with VIP did not produce an increase in fibrinolytic activity, while dextran sulfate (DS) and urokinase (UK) showed the activity. VIP solution placed on a plasminogen-rich fibrin plate did not show fibrinolysis. VIP had neither a plasminogen activator nor plasmin activity. VIP may release plasminogen activators into the blood. PMID- 2273654 TI - Role of the epithelium in airway hyperreactivity. PMID- 2273653 TI - Cerebrovascular reactivities to N-methylated catecholamines in humans, monkeys and dogs. AB - A comparison was made of the cerebrovascular responses of humans, monkeys and dogs to noradrenaline (NAd) and dopamine (DA) as well as to their N-methylated derivatives, adrenaline (Ad) and N-methyl dopamine (methyl DA). The present experiments demonstrated that N-methylation of both NAd and DA enhanced the contractile responses of these agents in human cerebral arteries, while only N methylation of DA enhanced the contraction of monkey cerebral arteries, and such an enhancement was not seen in dog cerebral arteries. PMID- 2273655 TI - [Airway smooth muscle responsiveness]. AB - Responsiveness of airway smooth muscle is influenced by various factors including autonomic nervous system, inflammatory cells and degrading enzymes. Hyperresponsiveness of airway smooth muscle may elucidated by functional abnormalities of inhibitory factors and abnormal production of potentiating factors. Up and down regulation of multiple factors may be the possible therapeutic approach to bronchial hyperresponsiveness. PMID- 2273656 TI - [The role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness in a guinea pig model of asthma]. AB - To elucidate the role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness (BHR) following antigen exposure, we have developed a guinea pig model of BHR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hrs before and 30 min before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine (Ach) was significantly increased. Histologic examination at 72 h showed a significant increase in the number of eosinophils but not neutrophils within the tracheal walls. However, there was no significant correlation between the change in bronchial responsiveness to Ach at 24 h and the number of eosinophil in the tracheal wall at 72 h. When guinea pigs were treated with Cyclosporin A or FK506, T-lymphocyte selective immunosuppressive agents, from the beginning of immunization period, both eosinophil infiltration and an increase in bronchial responsiveness were inhibited. These results suggest that eosinophils and T-lymphocytes may play an important role in the development of bronchial hyperresponsiveness. PMID- 2273657 TI - [Possible contribution of lung macrophage to airway hyperreactivity]. AB - To elucidate the possible contribution of lung macrophage to airway hyperreactivity, we studied the effect of canine pulmonary alveolar macrophages (PAM) stimulated with anti-dinitrophenyl (DNP) IgE antibody and DNP-human serum albumin on airway smooth muscle and epithelial functions in vitro. IgE-stimulated PAM increased the contractile responses of bronchial segments to electrical field stimulation and the short-circuit current of cultured tracheal epithelium, the former effect being abolished in the presence of the thromboxane A2 receptor antagonist and the latter inhibited by the leukotriene antagonist and the Cl transport blocker. These results suggest that PAM may increase the parasympathetic contraction and Cl secretion in the airway through IgE-dependent release of thromboxane A2 and leukotriene, respectively. PMID- 2273658 TI - [Long-term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis]. AB - The present study reviewed and summarized the long-term therapeutic effects of erythromycin or newquinolone antibacterial agents on diffuse panbronchiolitis. Various parameters before and after the treatment were analyzed in 101 patients selected from 227 diffuse panbronchiolitis patients gathered from 26 institutes in Japan. Patients had been treated with either erythromycin or newquinolone antibacterial agent for more than 3 months. Patients treated with erythromycin showed significant improvement of dyspnea on exertion, findings of chest X-ray, data on blood gas analysis, rate of ESR, titer of cold coagulation and amount of sputum, compared with patients treated with the newquinolone antibacterial agent. Among the patients treated with erythromycin, those patients with the initial high cold coagulation titer showed better improvement following treatment. However, there was no significant difference in improvement, depending upon either the duration between the time of onset of the disease, the initiation of treatment, and the initial severity of the disease. PMID- 2273659 TI - [Eosinophil colony stimulating activity induced by administration of interleukin 2 into the pleural cavity of patients with malignant pleurisy]. AB - Systemic administration of interleukin-2 (IL-2) in patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanisms of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and in eosinophil colony stimulating activity (Eo-CSA) in the pleural fluid of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma, during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and mild eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSA appeared in the pleural fluid before increase in the number of eosinophils. The Eo-CSA seemed to be a polypeptide or protein because it was trypsin-sensitive and had a molecular weight of 40-60 kDa. PMID- 2273660 TI - [Simultaneous bilateral spontaneous pneumothoraces]. AB - Seven cases (1.9%) of simultaneous bilateral pneumothoraces were found in a retrospective study of 377 patients with spontaneous pneumothorax during the period from July, 1977 to June, 1989. Their symptoms were essentially those of unilateral pneumothorax, but with more severe dyspnea. All but two cases, both young, had underlying pulmonary diseases. Three (two lung cancers and one metastatic lung disease) had malignant pulmonary disease. During this period, five lung cancer patients were complicated with pneumothorax, and two of them had simultaneous bilateral pneumothoraces. Therefore the frequency of bilateral pneumothoraces in the lung cancer patients associated with pneumothorax is high. In these three patients with malignant disease, tube drainage was carried out but all died of respiratory failure. Two senile patients had small bilateral pneumothoraces. Bed rest without invasive treatment led to successful cure. Two younger patients without underlying pathology initially underwent tube drainage, followed by operation. We conclude that many patients with simultaneous bilateral spontaneous pneumothoraces have underlying pulmonary disease, the frequency of lung cancer being particularly high. Young patients without underlying disease should be operated on following alleviation of symptoms by tube drainage. Older patients and patients with malignancy should be treated with great care and individually. PMID- 2273661 TI - [CA 19-9 in patients with benign pulmonary diseases]. AB - Although serum CA 19-9 is considered to be a useful and specific tumor marker for pancreatic cancer, some patients with benign pulmonary diseases show elevated serum CA 19-9 levels. We measured serum CA 19-9 levels of 156 patients with benign pulmonary diseases (55 with asbestosis, 11 with bronchial asthma, 32 with bronchiectasis, 16 with idiopathic pulmonary fibrosis (IPF), 13 with healed pulmonary tuberculosis (HPT) and 29 other benign diseases). The percentage of patients with positive serum CA 19-9 was 42.3% (14.5% in asbestosis, 27.3% in bronchial asthma, 59.4% in bronchiectasis, 81.3% in IPF, 61.5% in HPT and 51.7% in others). In some patients, serum CA 19-9 levels were as high as those found in malignant gastrointestinal diseases. Serum CA 19-9 levels correlated well with disease activity. Immunohistochemically, CA 19-9 was expressed in mucous cells of the bronchial gland and surface of the bronchiolar surface epithelium cells in benign pulmonary disease. Gel filtration study suggested some difference in molecular weight between the serum CA 19-9 antigen of lung cancer and that of benign pulmonary diseases. It is suggested that serum CA 19-9 increases in the case of hyperplasia of the bronchiolar epithelium cells or the mucous cells of the bronchial gland. We conclude that benign pulmonary disease is one of the factors that affect serum CA 19-9 levels. PMID- 2273662 TI - [Bronchoconstriction in isocapnic hyperventilation-induced asthma]. AB - It is well known that some asthmatic patients develop bronchoconstriction after exercise challenge (exercise-induced asthma, EIA). Recently, it has been pointed out that isocapnic hyperventilation also induces similar bronchoconstriction (hyperventilation-induced asthma, HIA) in the same asthmatic subjects. However, the mechanism of HIA has not yet been determined. In the present study, we performed exercise and hyperventilation challenge in the same patients and pulmonary function data and neutrophil chemotactic factor (NCF) in peripheral blood were examined before and after both challenges. Twelve asthmatic patients with normal pulmonary function data on testing days were subjected to exercise test on a bicycle ergometer and then isocapnic hyperventilation tests in subsequent days. Subjects breathed dry air from the cylinder. Isocapnic hyperventilation was performed by monitoring minute ventilation and each patient followed the same minute ventilation exercise. The reduction of FEV1.0 and time course of airway obstruction were almost the same after exercise and hyperventilation testing. All patients who developed EIA also developed HIA and other patients did not develop both EIA and HIA. Changes of Rrs, V50 and V25 and their time course after each test were also similar in EIA(+) and HIA(+), and in EIA(-) and HIA(-). NCF increased significantly after both challenges in EIA(+) and HIA(+) patient, although increment of NCF was much less these the increases of HIA(+). These data may suggest that the development of bronchoconstriction was compatible after exercise and hyperventilation in each asthmatic patient, however, the mechanism of HIA may differ from EIA, although NCF slightly but significantly increased in HIA, suggesting the possible role of a chemical mediator. PMID- 2273663 TI - [The penetration of ofloxacin and enoxacin into the alveolar spaces in rats]. AB - Ofloxacin (OFLX) or Enoxacin (ENX) was intramuscularly administered at a dose of 100 mg/kg to rats (normal and pneumonia model). Bronchoalveolar lavage (BAL) was performed at 30 min after administration and concentrations of OFLX or ENX in the recovery fluid were determined. Total recovery amounts of OFLX from 10 BAL procedures were 64.7 +/- 18.7 micrograms in the normal group and 126.5 +/- 16.1 micrograms in the pneumonia group, and the amounts of ENX were 15.6 +/- 4.6 micrograms in the normal group and 32.8 +/- 6.1 micrograms in the pneumonia group. Regarding the ratio of total recovery amounts in BAL to serum concentrations of OFLX or ENX, the pneumonia group was higher than the normal group and the ratio of OFLX was higher than that of ENX. Regarding the ratio of total recovery amount in BAL to the amount in lung parenchyma, the ratio of OFLX was higher than that of ENX, but there was no significant difference between the normal group and the pneumonia group in the ratio of OFLX or ENX. With regard to the ratio of the amount of OFLX or ENX in lung parenchyma to their serum concentrations, the ratio was higher in the pneumonia group than in the normal group, but there was no significant difference between OFLX and ENX. Based on the above results, it was concluded that the permeability of OFLX into epithelium of blood capillary is the same as that of ENX, but the permeability of OFLX into alveolus epithelium is superior to that of ENX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273664 TI - [A case of surgical treatment of multiple bilateral pulmonary arteriovenous fistulas in a senile patient]. AB - A 65-year-old woman was admitted with exertional dyspnea. She had a history of syncopal attack and cerebral infarction. On admission, her chest radiography ++ revealed two mass shadows in the right upper and lower fields. Pulmonary angiography and right heart catheterization were performed. Six arteriovenous fistulas in the right lung and five in the left were observed. The percent of R-L shunt was 51.5%. Because of exertional dyspnea, large shunt and history of cerebrovascular disorders, excision resection of two fistulas in right upper and middle lobes and right lower lobectomy were performed. Her symptoms improved and the percent of the R-L shunt markedly decreased after the operation. There is no sign of enlargement in size of the remaining arteriovenous fistulas. PMID- 2273665 TI - [Pulmonary infiltration with eosinophilia possibly induced by cefotiam in a case of steroid-dependent asthma]. AB - A 37-year-old female with refractory asthma taking betamethasone orally (1 mg/d), showed a fever of 38.5 degrees C, productive cough and dyspnea. The chest X-ray demonstrated diffuse infiltration in the left lower lung field. The WBC count was 16,000/mm3 with 6% eosinophils. She was treated with intravenous drip infusion of antibiotics (Cefotiam 2 mg/d and Sisomicin 150 mg/d) for 2 weeks, and her symptoms and the chest X-ray findings improved. However, at the end of the therapy eosinophilia was noticed. Sixteen days after the completion of antibiotic therapy, she again experienced fever, cough and dyspnea. The chest X-ray again demonstrated diffuse infiltrations in the left lower lung field. The total IgE level, histamine and circulating immune complex titers were elevated. The WBC count was 14,700/mm3 with 34% eosinophils. Although a sputum culture yielded no organisms, many eosinophils were observed in the sputum. There were no clinical or laboratory findings compatible with allergic broncho-pulmonary aspergillosis. After the administration of oral prednisolone (40 mg/d), the patient showed rapid improvement with resolution of all symptoms and normalization of the IgE, histamine and circulating immune complex levels. The chest X-ray revealed marked regression of the pulmonary infiltrations. A microscopic examination of a transbronchial biopsy specimen demonstrated moderate eosinophilic infiltrations. It was compatible with the diagnosis of pulmonary infiltration with eosinophilia. Treatment was performed with prednisolone. The result of a lymphocyte stimulation test was positive for Cefotiam. An in vitro test was performed to evaluate the diagnosis of drug allergy in this case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273666 TI - [A case of primary pulmonary hypertension with high venous thromboxane B2 concentration]. AB - A 30-year-old male was admitted because of dyspnea, which had started three years before the admission. Chest roentgenogram showed prominence of the proximal pulmonary arteries and diminished vascularity of the peripheral pulmonary arteries. Electrocardiogram showed right axis deviation and right ventricular hypertrophy. Right heart catheterization revealed a markedly elevated pulmonary arterial pressure and pulmonary vascular resistance with normal capillary wedge pressure. Oximetry showed no evidence of intracardiac shunt. Perfusion lung scan revealed nonsegmental, patchy defects in both lungs. Pulmonary arteriography showed no evidence of pulmonary thromboembolism. From the above findings, primary pulmonary hypertension was diagnosed. Nifedipine, ISDN, prazosin, and captopril were administered to evaluate the short term-effect of he vasodilators. Nifedipine was found to be the most effective. The venous thromboxane B2 level was high. After oxygen therapy, venous thromboxane B2 level fell within the normal range following improvement of arterial oxygenation and decrease in venous FDP level. Hemodynamic changes induced by ice-water hand immersion showed marked increase in the mean pulmonary arterial pressure and total pulmonary arterial resistance. These results suggested that chemical mediators such as thromboxane, and pulmonary arterial vasospasm were involved in the pathogenesis. PMID- 2273668 TI - [Anomalous origin of the right pulmonary artery from the ascending aorta: a report of three cases]. AB - Three patients with anomalous origin of the right pulmonary artery from the ascending aorta were reported. Case 1 was a 16-day-old girl with the right pulmonary artery arising from the base of the ascending aorta. Division and direct anastomosis of the anomalous vessel to the pulmonary trunk were successfully performed. Case 2 was a 4-month-old girl with the kinked and stenotic right pulmonary artery arising from the distal ascending aorta. At the time of surgery, however, the right pulmonary artery had been completely occluded and the pulmonary hypertension of the main pulmonary trunk had been disappeared. The chest was closed without any corrections. Case 3 was a 17-month-old girl with the stenotic right pulmonary artery arising from the distal ascending aorta. The stenotic lesion of the right pulmonary artery was longitudinally incised and anastomosed with the PTFE graft in an end-to-end fashion, followed by the end-to side anastomosis of the graft and the pulmonary trunk. PMID- 2273667 TI - [A case of polycythemia vera associated with idiopathic interstitial pneumonia successfully treated by alkylating agents]. AB - A 62-year-old female was referred to our division because of general fatigue, low grade fever and exertional dyspnea for 2 months. Laboratory data and chest roentgenograms on admission revealed polycythemia vera associated with idiopathic interstitial pneumonia. Alkylating therapy with carboquone and cyclophosphamide resulted in the improvement of abnormalities on chest X-ray films which had previously shown decreased lung fields and abnormal interstitial shadows, as well as hematological abnormalities. Six months later, the results of the patient's pulmonary function tests and arterial blood gas analysis became within normal limits. Little information about polycythemia vera associated with idiopathic interstitial pneumonia is available. This case indicated that alkylating therapy with no steroidal combination is effective for idiopathic interstitial pneumonia. PMID- 2273669 TI - [Coronary-coronary bypass (C-C bypass) in 2 cases]. AB - A left IMA graft to LAD associated with c-c graftings using saphenous vein were simultaneously performed in 70-year old man and 44-year-old man with multiple coronary disease. Postoperative catheterization showed patency in both cases. It is advisable to perform c-c bypass for patients with calcification of ascending aorta or stenosis of distal RCA such as 4-PD or 4-AV. PMID- 2273670 TI - [Percutaneous balloon valvuloplasty of a stenosed bioprosthesis (Carpentier Edwards xenograft) in the tricuspid valve position]. AB - Two patients with increasing stenosis of a bioprosthesis in the tricuspid valve position were treated by percutaneous balloon valvuloplasty (PBV). Tricuspid valve replacement with a Carpentier-Edwards xenograft and mitral valve replacement with a Duromedics mechanical valve had been performed in both of them 2 to 3 years prior to PBV. Echocardiographic studies revealed tricuspid bioprosthetic stenosis with a prolonged pressure half time. After PBV, the calculated valve area and cardiac index increased and the pressure half time was shortened, although improvement of clinical symptoms was not apparent. Complications related to the procedure did not occur. Further studies are required to determine the indications and to see the long term results of PBV on stenosed bioprosthesis in the tricuspid valve position, but for the moment, we consider PBV be tried with caution for a stenosed bioprosthesis in the tricuspid valve position before the decision for re-replacement of the prosthesis. PMID- 2273671 TI - [The use of the bio-pump with an interposed soft reservoir in replacement of descending thoracic aortic aneurysms]. AB - The centrifugal pump (bio-pump) as a temporary shunt during the operation of the descending thoracic aortic aneurysms was used as effective means of providing adequate circulation to the lower body. But in the acute excessive bleeding, estimates of the flow to the abdominal viscera as well as spinal cord are variable. We employed bio-pump with an interposed soft reservoir under low dose systemic heparinization in 2 cases of the descending thoracic aortic aneurysms. Both cases had been maintained adequate flow and perfusion pressure in the time of acute excessive hemorrhage, and there were no evidence of the organ failures due to microembolism. Furthermore, postoperative hemorrhage by using low dose heparin seemed to be unrisky. Compared with the previous method, bio-pump with an interposed soft reservoir provides adequate circulation to the lower body even if acute excessive bleeding occurred. PMID- 2273672 TI - [Four cases of spontaneous hemopneumothorax]. AB - We reported four cases of spontaneous hemopneumothorax. Of these, one (a 25-year old man) had right hemopneumothorax and three (a 28-year-old man, a 21-year-old woman and a 24-year-old man) had left hemopneumothorax. In one case, because massive intrapleural bleeding had continued, an emergency operation was performed. In two cases, thoracotomy was performed because of recurrent pneumothorax. In the other case, about one week after hemopneumothorax had been controlled by pleural drainage, pneumothorax recurred and thoracotomy was performed. In conclusion, early thoracotomy is the best treatment for spontaneous hemopneumothorax. PMID- 2273673 TI - [Familial cardiac myxoma with multiple and contralateral recurrence]. AB - This report described a familial recurrent cardiac myxoma involving mother and daughter. The mother, at 27 year of age, had developed recurrent multiple myxomas in both left and right atrium and right ventricle 4 years after surgical excision of left atrial myxoma. Excision was successful and remains well without signs of recurrence 9 years postoperatively. In an asymptomatic 13-year-old daughter, a recurrent left atrial myxoma was found 3 years after the excision of right atrial myxoma by echocardiographic follow-up at 6 month intervals. Excision of left atrial myxoma was performed and histology showed the essentially the same findings as primary myxoma without signs of malignancy. From an experience of this familial recurrent myxoma and a review of 38 cases of 17 familial cardiac myxoma, it is recommended that wide excision of tumor including surrounding tissues, thorough search for multiple heterotopic tumors at surgery, close postoperative echocardiographic follow-up for at least 5 years, and examination of skin and breast tumor, and endocrine disorder for "complex" myxoma. PMID- 2273674 TI - [A case of intimal dissection of the left internal mammary artery grafting]. AB - A 73-year-old man underwent reoperation using the in situ left internal mammary artery (IMA) because of the stenosis of the vein graft to the left anterior descending artery (LAD). The patient recovered free from angina but angiography performed 1 month after operation revealed the dissection of intima of the left IMA. Use of the IMA in coronary artery bypass grafting (CABG) is now generally accepted as the optimal method of myocardial revascuralization and the use of the left IMA to the LAD has become a routine procedure in our CABG surgery. However, because the IMA wall is friable and disruption occurs easily, especially in the elder, much care should be taken during mobilization of the IMA. PMID- 2273675 TI - [Case report of the superior approach for correction of the supracardiac type of total anomalous pulmonary venous drainage (TAPVD) in the neonatal period]. AB - An eleven-day-old newborn with cyanosis and respiratory distress was admitted. Intubation and catecholamine administration had already done. Blood pressure was 80/50 mmHg, heart rate was 160/min. Urine volume was only 7 ml per 4 hours with diuretics. The diagnosis of supracardiac type of TAPVD was done by echo cardiography. Without cardiac catheterization, emergent operation was performed. After median sternotomy, the mobilization of the aorta was done. Under cardiopulmonary bypass the aorta was retracted to the left, the superior vena cava to the right and the common pulmonary venous trunk (CPV) was identified through the transverse sinus. Parallel incision were made in the left atrium and CPV, and extended to the vertical vein. An anastomosis using continuous suture was fashioned. She had a good postoperative course. The superior approach through the transverse sinus affords excellent exposure of the CPV and left atrium in situ in the neonatal period, if the mobilization of the aorta is completed, and the heart is not compressed or displaced. This approach is useful for supracardiac type of TAPVD. PMID- 2273676 TI - [A case of ruptured azygos vein and diaphragmatic hernia due to blunt chest trauma]. AB - A 47-year-old female was admitted to the emergency room following an automobile accident. She was shocked complaining of respiratory difficulty and chest pain. A chest X-ray showed right hemothorax which drained 2.5 liters of blood on insertion of chest tube. Emergency operation revealed rupture of azygos vein. The bleeding was controlled by the ligation of the azygos vein. Postoperative chest X ray showed obscuration of the left diaphragma, and herniated stomach was identified by the gastrography. Second operation was performed and ruptured diaphragma was repaired. Her postoperative recovery was good. She was discharged from hospital at 7th week. PMID- 2273677 TI - [Successful management of a ruptured infected aneurysm of the thoracic aorta: report of a case]. AB - A successful removal of the infected thoracic aortic aneurysm ruptured to the lung is reported. A 59-year-old man who had been suffering from high fever showed sudden hemoptysis and shock during antibiotic therapy. Immediately a so-called temporary bypass grafting from ascending aorta to descending aorta was placed with a woven Dacron prosthesis, and then aneurysmectomy with upper lobectomy of the left lung was carried out. Finally the graft was left as a permanent bypass graft. In addition, the left subclavian artery was reconstructed with a EPTFE graft. The patient is now well one year after operation. PMID- 2273678 TI - [Application of an extended aortic arch anastomosis for staged repair of type A interruption: a case report of a 13-day-old neonate]. AB - A 2-day-old girl was found to have a type A interruption of aortic arch, ventricular septal defect and patent ductus arteriosus with severe metabolic acidosis. Following aggressive medical treatment with Prostaglandin E1 and inotropic agents, she underwent arch reconstruction by extended aortic arch anastomosis and pulmonary arterial banding on her 13th day. Six months after first stage repair, a subarterial infundibular VSD was closed transpulmonary and reconstruction of pulmonary artery was done by end-to-end anastomosis. She shows normal development, strong femoral pulse and no neurologic sequelae after 8 months postoperatively. PMID- 2273679 TI - [Management of coronary artery bypass grafting surgery by continuous ambulatory peritoneal dialysis in a patient with chronic renal failure under hemodialysis]. AB - A 64-year-old patient with chronic renal failure underwent coronary artery bypass grafting (CABG) because of the frequent severe angina during hemodialysis. Intraoperative hemodialysis and extra-corporeal ultrafiltration method (ECUM) was used during cardiopulmonary bypass. Postoperative management was successfully performed by continuous ambulatory peritoneal dialysis (CAPD), which made hemodynamics stable and prevented postoperative bleeding, providing with adequate fluid removal and satisfactory control of serum chemistry. PMID- 2273680 TI - [A successful removal of a left atrial massive ball thrombus caused by mitral stenosis]. AB - A 66-year-old female with a mitral stenosis and a left atrial massive ball thrombus is presented. She was admitted due to a transient right hemiplegia and a speech disturbance. This thrombus had been detected preoperatively by an echocardiogram and a left atriography. A mitral valve replacement using a Bjork Shiley valve 27 mm, accompanied with the removal of the thrombus was performed. The ball thrombus was dark red, 55 x 35 x 32 mm in size and 15 g in weight. After the surgery, the patient progressed well. Because of the high frequency of peripheral embolism and of sudden death, a left atrial ball thrombus should be removed immediately. PMID- 2273681 TI - [Right ventricular myxoma complicated by paroxysmal atrial tachycardia: a surgical case report]. AB - A rare case of right ventricular myxoma complicated by paroxysmal atrial tachycardia (PAT) is presented. A 13-year-old boy was referred to our hospital because of the recurrent episodes of PAT. Every available medical treatment was tried to reverse the PAT, during which an abnormal mass in the right ventricle was found by echocardiography. Subsequently magnetic resonance imaging computed tomography demonstrated that the tumor developed from the anterior wall of right ventricle with a pedicle. A 10 g of reddish myxomatous mass originating from the base of anterior papillary muscle was resected including the stalk during total cardiopulmonary bypass. The transient paroxysmal atrial tachycardia developed shortly after operation, however, tachycardic episode has never recurred after that. It is noteworthy that intracardiac evaluation is necessary when there is longstanding and inveterate tachyarrhythmia in otherwise healthy children. PMID- 2273682 TI - [Clinical study on abnormalities of lower esophageal sphincter (LES) function in infancy and childhood with special reference to gastroesophageal reflux]. AB - For the purpose of clarifying lower esophageal sphincter function, which is representative of antireflux competence, 51 normal newborn and early infants and 28 newborn and infants with gastroesophageal reflux were examined by standardized manometric studies. Barium studies and 24-hour pH monitoring in the distal esophagus were also performed, and the following results were obtained. 1) In normal infants, there was no correlation between LES pressure and age, but LES length increased with age. 2) LES Pressure of GER infants (22.2 +/- 6.4 cmH2O) was lower than normal infants (37.6 +/- 8.8 cmH2O). This indicated LES function was lower in GER infants. 3) In GER infants, LES pressure increased to within normal range with clinical improvement. The critical point of LES pressure was 27 cmH2O. 4) In radiological studies in GER infants there was no correlation between the grade of Barium regurgitation and LES pressure, or between HIS angle, Fornix Index and LES pressure. 5) On 24-hour pH monitoring, pH score of GER infants was very much higher than that of normal infants. LES incompetence din GER infants was also recognized in this investigation. Esophageal manometric study was very useful for diagnosis of LES dysfunction and assessment of therapeutic effect. For evaluation of anti-reflux cardiac function, multiple approaches were valuable, including not only manometric studies but also radiologic studies and 24-hour pH monitoring. PMID- 2273684 TI - [Study on function of aganglionic colon musculature of Hirschsprung's disease murine model]. AB - This study examined the function in vitro of aganglionic colon musculature in mice with hereditary aganglionosis--a strain of animals used as a model of Hirschsprung's disease. Double sucrose gap recordings from the muscle strips of both normal and aganglionic colon showed bursts of spike potentials with muscle contraction. Intracellular recordings of the membrane potentials of the circular muscle cells of normal, aganglionic and oligo-ganglionic colon had no statistical difference. Microelectrode recordings from the circular muscle cells of normal siblings, in the presence of nifedipine, irregular ongoing fluctuations in membrane potential, which were abolished by tetrodotoxin and reduced by d tubocurarine or apamin. The fluctuations were less effected by atropine. These observations suggest that there is ongoing inhibitory neural activity to the circular smooth muscle of normal colon. These ongoing fluctuations were not recorded from the cells of aganglionic and oligo-ganglionic colon of affected animals. Although transmural stimulation of the intrinsic nerves produced cholinergic excitatory and inhibitory junction potentials in normal colon, no junction potentials were evoked by transmural stimulation in aganglionic colon. It was concluded that the ongoing tonic inhibitory activity may contribute to the compliance of the normal mouse colon and lack of the compliance may affect functional intestinal obstruction of the aganglionic colon in Hirschsprung's disease. PMID- 2273683 TI - [Effects of cisapride on gastric emptying]. AB - To evaluate the effects of cisapride on gastric emptying, gastric emptying was measured in six healthy volunteers using radioisotopic techniques which were established three areas of interest, i.e. the whole stomach, the proximal stomach and the antrum. Following results were obtained. 1. At the half emptying times, cisapride induced a more rapid gastric emptying than did placebo in 5 of 6 volunteers. 2. By analyzing gastric emptying curves obtained from three areas of interest, it was suggested that cisapride enhanced the transfer of gastric contents from the proximal stomach to the antrum together with the antral emptying, so that gastric emptying was accelerated. PMID- 2273685 TI - [Manometric study of vertical banded gastroplasty for morbid obesity]. AB - Morbidly obese patients undergoing vertical banded gastroplasty were studied preoperatively and/or postoperatively to characterize its manometric pattern. The esophageal manometry using station pull through technique involved 14 preoperative patients with a mean age of 28 +/- 7 years who were a obesity index of 220 +/- 32% and 14 postoperative patients with a mean age of 30 +/- 7 years who were a obesity index of 158 +/- 23%. Preoperative lower esophageal sphincter (LES) pressure using gastric base line as O was 16.1 +/- 8.5 cmH2O and a LES length of 3.4 +/- 0.9 cm. Postoperatively, the vertical banded gastroplasty channel had a pressure of 17.7 +/- 7.1 cmH2O and a length of 8.2 +/- 1.7 cm which was higher than gastric base line. No difference was seen between preoperative LES pressure and postoperative channel pressure, however postoperative channel length was significantly (p less than 0.01) larger than preoperative LES length. We concluded that vertical banded gastroplasty for morbid obesity created a longer high pressure zone in accordance with channel which would inhibit reflux of gastric juice. PMID- 2273686 TI - [Relationship between secretory and motility functions of the colon]. PMID- 2273687 TI - [Abstracts of papers at XXXI annual meeting of Japan Society of Smooth Muscle Research. October 3,4, 1990, Fukuoka City]. PMID- 2273688 TI - [Effects of dopamine D2 receptor antagonists on gastrointestinal motility]. PMID- 2273689 TI - [Effect of acute and long-term administration of a stimulative agent on gastrointestinal motility in the therapy of patients with diabetic gastroparesis]. PMID- 2273690 TI - [Effects of cisapride on upper-gastrointestinal motility and digestive hormones]. PMID- 2273691 TI - [Effects of gastrointestinal-motility control agents on gastroesophageal reflux]. PMID- 2273692 TI - [Clinical effects of gastrointestinal-motility stimulating agents on non-ulcer dyspepsia]. PMID- 2273693 TI - [Comparative study of effects of gastrointestinal-motility control agents on rats and human colon]. PMID- 2273694 TI - [Mechanism of action of trimebutine maleate on gastro-colic reflex in patients with irritable bowel syndrome]. PMID- 2273695 TI - [Urinary incontinence: a review]. PMID- 2273696 TI - [Clinico-bacteriological studies on the etiology of bacterial prostatitis. I. The distribution of clinical isolates and bacteria-specific immunoglobulin in EPS]. AB - The distribution of clinical isolates from patients with prostatitis and pathogenicity of the isolates were studied. A new method for measuring the bacteria-specific immunoglobulins in expressed prostatic secretion (EPS) was developed and used for the detection of local immuno-reaction against pathogenic bacteria in the cases with prostatitis. There were no cases with increased antibodies specific for gram-positive cocci (GPC), indicating that the pathogenecity of GPC in bacterial prostatitis was doubtful. On the other hand, specific antibodies against gram negative rods (GNR) were elevated in all cases with acute prostatitis and changes of the antibody titers were correlated well to clinical courses. The present clinico-statistic and immuno-biological studies re confirmed that E. coli was the main organism in uncomplicated bacterial prostatitis. PMID- 2273697 TI - [Clinical studies of methicillin resistant S. aureus (MRSA) infections during the recent 10 months in our department]. AB - Recently MRSA occupies a prominent position in nosocomial infections. We experienced 9 cases of severe MRSA infections in our department during the 10 months from Apr. 1989 to Jan. 1990. We investigated the clinical background of them. THE RESULTS of studies were as followed: 1) All cases were inpatients. 2) All cases were considered to be compromised hosts. 3) In 7 cases many kinds of catheters and apparatuses were pre-indwelt . 4) In 8 cases over 2 kinds of antibiotics and in 7 cases 3rd generation cephems were pre-administered. 5) The 5 cases, who were selected for coagulase typing, all belonged to type II. 6) All cases had almost similar patterns of drug sensitivity and were resistant to large amounts of antibiotics. All cases had good sensitivity to minocycline. 7) THE RESULTS: 3 died of sepsis and respiratory failure and 6 were alive (MRSA strains were still isolated in 3 cases and were eradicated in the other 3 cases 1-4 months after the therapy was started). PMID- 2273698 TI - [In vitro effects of epidermal growth factor (EGF) on growth of urological malignant tumor cells]. AB - It is well known that Epidermal Growth Factor (EGF) is a cell-regulating factor for variety of tissues in vitro including normal and malignant cells. Furthermore, Takano et al reported that a decreased expression of EGF receptor in clones of human cancer KB cell line might be one of the pleiotropic properties of multidrug-resistant cells. However, both the influence of EGF on human urological cancer cell lines and the relation between EGF receptors and sensitivities of antitumor drugs on these cell lines have not been fully described. We have studied the effects of EGF on growth of 4 transitional carcinoma cell lines of bladder (TCCaB), 1 squamous cell carcinoma cell line of bladder (SCCaB), 5 renal cell carcinoma cell lines (RCC) and 3 prostatic carcinoma cell lines (CaP), as well as the relationship between the number of EGF receptors and drug sensitivities of these cell lines in vitro against methotrexate, vinblastine, adriamycin, cisplatin and etoposide (VP16). The present results determined by the in vitro colony forming efficiency method showed that exogenous addition of EGF to cell cultures at 0.1 ng/ml stimulated the growth of SCCaB by 169.0%, and at 1 ng/ml inhibited that of RCC by 2.9%-79.0%, relative to control. The more EGF receptors by 125I-EGF binding assay, the higher inhibition of VP16 on the growth of these cell lines. These results suggested that EGF stimulated the growth of SCCaB and inhibited the growth of RCC in vitro, and we found that these phenomena were correlated with neither the number of EGF receptors nor affinities of that receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273699 TI - [Cyclosporin levels in semen of renal transplant patients]. AB - Cyclosporin (CsA) has powerful immunosuppressive properties, and its recent application to organ transplantation has resulted in markedly improved graft survival. However, CsA has certain adverse side effects, the most notable being nephrotoxicity and hepatotoxicity. Among other untoward effects, little is known about the effects of CsA on the reproductive organs. Since good graft survival is now expected with CsA, the long term effect of the drug on the gonads should be monitored carefully, particularly for young recipients. Prior to investigation of the effect of CsA on the testis, the level of CsA in semen of the adult renal transplant patients were measured. Twelve samples of semen from eight recipients, mean age 35 (SD 9), were collected by masturbation in the morning just before taking CsA after more than 5 day abstinence, and it was frozen at -80 degrees C. They had been taking immunosuppressants that were a combination of either CsA and prednisolone, or CsA, azathioprine and prednisolone for 5 to 63 months. The dose of CsA was 3.7 mg/kg to 5.0 mg/kg. The range of the level of serum creatinine was 1.1 mg/dl to 2.9 mg/dl. CsA in whole blood was measured by high performance liquid chromatography (HPLC), and CsA in semen was also measured by HPLC after extracting CsA with diethylether. The level of CsA in semen was 27 ng/ml to 165 ng/ml and that in whole blood was 51 ng/ml to 133 ng/ml. The relation between both levels was linear (r = 0.68, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273700 TI - [A study on the hemodialysis period following cadaveric kidney transplantation--a comparison between two centers sharing cadaver donor kidney pairs]. AB - To study the hemodialysis period following cadaveric renal transplantation, we reviewed 18 consecutive cadaver donor kidney pairs of which one kidney was transplanted at Shiga University of Medical Science (SUMS) while the contralateral kidney was transplanted at Kyoto Prefectural Medical University (KPMU) between January 1983 and September 1988. Of these 18 pairs, graft function was satisfactory and the recipient was free from hemodialysis in 13 pairs. However, the postoperative hemodialysis periods were different between the two centers. To clarify the factors causing this difference, recipient factors, such as age, HLA matching, total ischemic time of the graft (TIT), immunosuppression, onset of diuresis and postoperative complications were studied. There were no significant differences in age, HLA matching, or immunosuppression. TIT of cases at SUMS was significantly longer than that of cases at KPMU. The postoperative hemodialysis period at SUMS was 25.8 days and that at KPMU was 17.8 days, however, the difference was not statistically significant. The results of this study indicate that TIT seems to be a major factor relating to delayed graft function in cadaveric renal transplantation. PMID- 2273702 TI - [Role of pulse volume recording in the evaluation of penile blood flow]. AB - Pulse volume recordings were obtained in 53 patients who were hospitalized with urological disorders other than impotence. This method seems to record the total blood volume changes in the penis. Pulse volume recordings also were found to correlate with the value of Penile Brachial pressure Index (PBI). Therefore, it proved to be valuable for estimating penile perfusion. Pulse volume recording is a simple, reliable and adaptable screening method for abnormal penile blood flow. Further investigation is necessary to determine the precision with which the method can detect abnormality of penile blood flow in patients with abnormal venous return. PMID- 2273701 TI - [Serum and tissue levels of placental alkaline phosphatase in patients with testicular tumor]. AB - Placental alkaline phosphatase (PLAP) levels in sera and tissues from 40 patients with testicular tumor were measured using a monoclonal immuno-catalytic assay. The mean value of the PLAP levels of seminoma tissues was found to be 92-fold higher than that of normal testes, being significantly high compared with that of non-seminoma tissues. The mean value of the serum PLAP levels from patient's with seminoma was also significantly higher than that from patients with non-seminoma. In 2 groups of seminoma and mixed type tumor containing seminoma and non-seminoma components, the PLAP levels of tissues from patients who had high levels of the serum PLAP (greater than or equal to 100 mKAU) were significantly higher than those from patients who had normal serum PLAP levels (less than 100 mKAU). In the seminoma or mixed type tumor groups, the serum PLAP levels of all patients who had high levels before treatment decreased to within a normal range after orchiectomy with or without chemotherapy or radiation therapy. We conclude that PLAP seems to be an useful tumor marker for the diagnosis and the monitoring of response to treatment in patients with seminoma. PMID- 2273703 TI - [The changes of population and distribution of S-phase cells in precancerous lesions of rat bladder revealed by the method of bromodeoxyuridine labeling]. AB - We studied whether bromodeoxyuridine (BrdU)-labeling method showing the population and/or distribution of S-phase cells in tumor tissues is useful to detect the precancerous lesions of bladder. The bladder lesions were induced by 0.05% N-butyl-N (4-hydroxybutyl) nitrosamine (BBN) in drinking water for ten weeks in five male rats (Wistar-Imamichi). BrdU (50 mg/kg) was injected to intraperitoneal space two hours before the resection of the bladder. The detection of positive cells (S-phase cells taking BrdU) was performed by peroxidase-antiperoxidase method. From five bladder specimens 144 lesions (simple hyperplasia (S)-73, papillary or nodular hyperplasia (PN)-57, papilloma (Pa)-14) were analysed. The labeling index (the ratio of positive cells to all epithelial cells in one lesion) showed no significant difference among the lesions (S, PN, and Pa). For analyses of the distribution patterns of S-phase cells, we investigated whether positive cells aside from basal layers and/or the serial positive cells in basal layers were seen or not in each lesion. The ratios of lesions containing positive cells aside from basal layers were 11% (8/73), 60% (34/57) and 100% (14/14) in S, PN and Pa lesions. The serial positive cells in basal layers were observed in 6% (4/73), 25% (14/57) and 50% (7/14) of S, PN and Pa lesions. Those differences were statistically significant. Above mentioned results suggest that the appearance of S-phase cells aside from basal layers and/or the serial S-phase cells in basal layers is characteristic change in precancerous lesions, which is useful for sooner detection of bladder carcinogenesis. PMID- 2273704 TI - [A clinical study on urethral recurrence observed after cystectomy]. AB - A clinical study was made on 108 male patients who underwent cystectomy. The posterior urethra and partial anterior urethra were removed in 47 cases, half of the perpendicular urethra was removed in 13 cases and the anterior urethra up to the fossa navicularis was removed in 48 cases. Out of 60 cases without urethrectomy, urethral recurrence was observed in 13 cases (21.7%), while no recurrence was observed in the cases treated with urethrectomy. The average period of time from cystectomy to urethral recurrence was 24.7 months (11-39 months). Urethral cancer of such early stages as pIa and pIb were found in 3 and 6 cases, respectively. Stage pT2 was found in 4 cases. Grade 1 cancer was found in 3 cases, grade 2, in 5 cases, and 3 in 5 cases. The proximal end of the perpendicular urethra was found to be the most frequent site for recurrence with 11 cases exhibiting recurrence at this location and 2 cases at the mid-portion of the perpendicular urethra. Many cases exhibited multiple recurrence of tumor of visually grayish, velvety and non-papillary type which was histologically all transitional cell carcinoma. Bladder tumor with higher grade tended to cause urethral cancer recurrence with higher grade. Bladder tumors at multiple locations from the trigone to the lateral and posterior walls tended to cause recurrence in the urethra (p less than 0.05). Of all the cases, 10 cases underwent urethrectomy and 2 cases penectomy. 12 cases received chemotherapy and 5 cases radiation therapy as postoperative adjuvant treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273705 TI - [Histological effects of endocrine therapy on prostatic cancer]. AB - Histological effects of endocrine therapy were evaluated in one hundred and four prostatic cancer patients by new criteria presented by the committee of "General Rule for Clinical and Pathological Studies on Prostatic Cancer". Route and time of biopsy, clinical stage and histological grade were related to histological effects. Biopsy specimens taken within three months from the start of the therapy tended to score rather low marks and this tendency is especially apparent with low grade cancers. Histological effects evaluated by the present method correlated well with prognosis in localized stages (stage B, C and D1). In metastatic cases, however, local effects were not related to the prognosis. PMID- 2273706 TI - [Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer]. AB - Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer. PMID- 2273707 TI - [Effects and side effects of ureteral stenting during extracorporeal shock wave lithotripsy]. AB - We retrospectively studied the effects and side effects of placing indwelling ureteral stents in 196 cases who underwent extracorporeal shock wave lithotripsy with a ureteral stent. The average period of ureteral stenting was approximately 22 days. Placing ureteral stents was mainly for large renal stones (79.3%), single kidney etc. There were no significant differences between the stunted and non-stunted patients with approximately 2 cm sized single renal stone with respect to the stone free rate, stone free period, and symptoms during stenting, which suggested that ureteral stenting might be unnecessary in those patients. High fever was highest in incidence of the symptoms and complications during stenting (17.2%). It occurred frequently in patients with infected stones or cystine stones. The percentages of pyrexia and stone street in patients using Towers type's stents were higher than those using the others. It was also shown that the bladder portions of the stents in patients using Towers peripheral ureteral stents were densely encased in calculous material and were very brittle. Fortunately the ureteral portions were removed intact. This study suggests that use of an indwelling ureteral stent may not contribute to the higher rate of being free of stones after the treatment of small to medium sized renal calculi, and that stents should be removed or changed early. PMID- 2273708 TI - [A 17-year experience with ileal conduit urinary diversion--early and late complications]. AB - A series of 185 patients, 133 males and 52 females, were treated by ileal conduit urinary diversion in the past 17 years. The patients ranged in age from 7 months to 81 years with an average of 59 years. Diversions were performed for malignant diseases in 174 patients, 85% of whom underwent a simultaneous radical surgery. The follow-up covered the postoperative period from 4 months to 16 years 8 months with an average of 4 years 8 months. Six patients (3%) died within 1 month of operation, and 43 of a total of 58 mortal cases died of cancer thereafter. The survival rates of 143 patients with bladder cancer were 84% for 1 year, 72% for 3 years, 67% for 5 years, 62% for 10 years and 54% for 15 years. Early complications were noticed in 38% of the patients. Delayed wound healing due to local infection (20%) and intestinal obstruction (10%) were the two major complications in this period. Late complications were encountered in 51% of the patients. Mild peristomal dermatitis (22%) and gradually developing renal complications (22%) are two major problems in the standard ileal conduit urinary diversion. The latter was significantly more frequent in patients who underwent the operation between 1973 and 1981 than in those who had the surgery between 1982 and 1989. Postoperative hydronephrosis was observed in 15 (13%) of 117 patients who showed normal urograms preoperatively. Ileoureteral reflux was observed in 50% of the cases with nonobstructing conduits, while it increased up to 70% along with obstruction of the conduit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273709 TI - [Aspiration biopsy of regional lymph node in bladder cancer]. AB - Percutaneous transabdominal fine needle aspiration biopsy (FNAB) of the pelvic and retroperitoneal lymph nodes was performed in 116 patients with bladder cancer. Metastasis to the regional lymph nodes was determined by this method in 21 patients. FNAB was positive in 10 of 12 patients having unequivocally positive or highly suspicious lymphogram, and in 11 of 104 patients (11%) having normal lymphogram. The results of FNAB were compared to the finding of lymph node dissection (LND) in 51 patients. FNAB and LND were negative in 43 patients and positive in 5. Two patients were FNAB negative but LND positive, and the remaining one case was FNAB positive but LND negative. The correlation between cytological diagnosis of FNAB and histological diagnosis of LND was 94 per cent. The survival rate of the cases of FNAB positive and lymphography negative was significantly higher than that of lymphography positive (p less than 0.01). The metastatic site of 5 cases with bladder cancer who are alive now without disease after more than 3 years was under the common iliac node and the number of the involved nodes was within 3. PMID- 2273711 TI - Gestational infirmities: the birth of new litigation. PMID- 2273710 TI - [Ectopic production of human chorionic gonadotropin by poorly differentiated transitional cell carcinoma of the renal pelvis]. AB - Herein we report a case of ectopic production of hCG by poorly differentiated transitional cell tumor of the renal pelvis. The patient was a 55-year-old male who had been diagnosed at another hospital as having giant hydronephrosis and renal stones and was referred to our hospital. The plain abdominal CT showed a low-density mass at the lower pole of the right kidney. His serum hCG level was as high as 120 mIU/ml. Transperitoneal nephrectomy was performed on July 7, 1987. Histopathological examinations showed the presence of squamous metaplasia within a high-grade transitional cell carcinoma, and immunohistochemical studies revealed the presence of chorionic gonadotropin in some giant cells. Two courses of combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC regimen) were given to him from the third week after the operation. However, he died of debility with distant metastasis 6 months after the operation. As far as we know, this is the third reported case in Japan. PMID- 2273712 TI - The Nursing Home Reform Act. PMID- 2273713 TI - Erythromycin and gastroparesis. PMID- 2273714 TI - Anesthesia mishaps. PMID- 2273715 TI - Urge your patients to have mammograms. PMID- 2273716 TI - Wide-QRS tachycardia with LBBB configuration. PMID- 2273717 TI - [Concomitance of coronary artery disease with acquired aortic valve disease]. AB - Incidence of concomitant coronary disease and extent of coronary artery lesions were assessed in 250 patients with acquired post-rheumatic aortic valve disease treated between 1976 and 1986 in National Institute of Cardiology. Patients' age ranged from 30 to 72 years. Hemodynamic examination with selective coronarography were performed in patients with typical effort or rest angina pain, with electrographically documented myocardial infarction in the past and also in those without (CAD clinical symptoms, but older than 45 years. Patients were divided into two groups: with isolated or dominated aortic valve stenosis (139 patients) and with isolated or dominated aortic valve incompetence. Patients younger and older than 45 years were separately analyzed. Concomitant CAD was proved if at least one coronary artery stenosis was stated. Lesions degree was proportionally graded: stenosis more than 70%, between 50-70% and 20-50% of a vessel lumen in relation to its diameter before lesion. Data were analyzed using ICL ME 29 computer. Study results indicate, that symptoms of coronary failure were observed in 82.8% of patients with acquired aortic valve disease. In 37% of cases there were critical stenoses requiring simultaneous aortic valve replacement with coronary artery by-pass grafting. Severe coronary artery stenosis was stated in 45% of patients with dominated or isolated aortic valve incompetence, whereas only in 29.3% with dominated or isolated aortic valve stenosis. 88.5% of patients younger than 45 years nevertheless coronary failure symptoms had normal coronary arteries. PMID- 2273718 TI - [Application of doppler ultrasound in diagnosis of aortic and pulmonary valve stenosis]. AB - 120 children (58 boys, 62 girls) aged 2 days-12 years (mean 3.5 +/- 3 years) with pulmonary or aortic valve stenosis underwent the study. Diagnosis was proved by a cardiac catheterization and angiography. There were determinated maximal flow velocities and pressure gradients through stenosed valve using the doppler ultrasound method. Values were compared with those obtained from cardiac catheterization. There were no statistically significant differences between these two methods. Increased blood flow velocities through the aortic or pulmonary valves were stated in the examined group comparing with healthy individuals. Obtained results prove Doppler method usefulness in diagnosis of aortic and pulmonary valve stenosis. In pulmonary valvular and subvalvular stenosis the Doppler method is useful for estimation of outflow tract obstruction while in a extreme case a results can be incompetent. PMID- 2273719 TI - [Value of echocardiography in detection of vegetation and their clinical significance]. AB - The aim of the study was to assess usefulness of echocardiography in bacterial vegetations detection as well as their clinical value as the indicator for surgical treatment. 44 patients aged 16-65 (mean 37.6) with infective mitral and aortic valve endocarditis underwent the study. Authors assessed clinical state taking into consideration blood culture tests as well as M-mode and parasternal and apical projections two-dimensional echocardiographic examinations. Data were compared with intraoperative or pathomorphological findings to estimate specificity and sensitivity of echocardiography in bacterial vegetation detection. Vegetations were pathomorphologically or intraoperatively stated in 21 patients (48%). M-mode echocardiography revealed changes in 16 patients, and two dimensional one in the next 3. In the group of 23 patients without vegetations, concordance between intraoperative findings and echocardiographic results was stated in 19 subjects. Therefore, sensitivity and specificity of two-dimensional echocardiography were respectively 91% and 83%. Vegetations stated in two dimensional echocardiographic examination had an unfavourable prognosis. Embolic complications were observed in 14, and myocardial infarction in 7 of 21 patients with bacterial vegetations. Authors thought it advisable to early operate on such patients. Whereas in patients without vegetations embolic complications were stated only in 3, and myocardial infarction in 1 patient. Therefore two dimensional echocardiography making bacterial vegetations detection possible in patients with infective valve endocarditis allows to identify patients with higher risk of thromboembolic complication or death. PMID- 2273720 TI - [The degree of functional circulatory failure according to NYHA classification and the state of hemodynamic disorders in constrictive pericarditis]. AB - Selected indices of left and right ventricular function and pulmonary circulation have been compared in two groups of patients with constrictive pericarditis: i.e. in 10 patients classified as NYHA functional class II and 13 patients as NYHA class III. The patients with NYHA class III showed higher average values of left ventricular end-diastolic pressure (mean + 19.4 vs 11.4 mm Hg) and right ventricular end-diastolic pressure (mean + 17.3 vs 9.5 mm Hg) as well as pulmonary systolic (mean + 39.5 vs 24.5 mm Hg) and diastolic pressure (mean + 20.6 vs 9.9 mm Hg). Mean total pulmonary resistance and left and right ventricular stiffness indices were slightly higher whereas cardiac index was slightly lower. Complaints of patients with constrictive pericarditis, fatigability and dyspnea are to a large extent determined by the level of end diastolic pressure in both ventricles and pulmonary hypertension that is by similar direct mechanism as in congestive heart failure. PMID- 2273721 TI - [Prognostic value of QT-QS2 index in the assessment of sudden coronary death]. AB - 200 patients aged 49 +/- 8 with coronary artery disease underwent selective coronarography, left ventriculography as well as performed every year laboratory, polycardiography, ECG exercise test, 24-hour ECG Holter monitoring and X-ray chest examinations. Mean follow-up period was 34 +/- 10 months. For QT-QS2 index monitoring patients were divided into two groups: I--with abnormal index QT greater than QS2 (61-30%) and II--with the normal one QT less than QS2 (139-70%). Lown's classification was applied for ventricular premature beats assessment. Left ventricular contractility was estimated in hemodynamic examination. 28 patients died due to cardiac reasons during follow-up (14%). Among 19 suddenly died patients (9.5%) 7 had a normal and 12 an abnormal QT-QS2 index. Sudden mortality rate was 5% in the normal QT less than or equal to QS2 subgroup, and 20% in the abnormal QT greater than QS2 one. These differences are statistically significant. PMID- 2273723 TI - [Echocardiographic image of cardial amyloidosis]. AB - Heart is involved nearly in 90% of acquired, systemic amyloidosis in a course of plasmocytoma, monoclonal gammapathy, Waldenstrom's disease and others immunological disorders. In classical acquired systemic amyloidosis due to chronic bacterial infection and other inflammatory states heart involvement is observed in 54% of patients. Authors presented a case of cardiac amyloidosis coexisting with hepatomegaly and nephropathy due to plasmocytoma. Diagnosis was based on the echocardiographic examination to which the patient was sent as the unstable postinfarction angina. Echocardiographic image typical of amyloidosis revealed such changes as: concentric both ventricular hypertrophy, generalized contractility impairment, thickness of intraatrial septum and pericardium with minimal effusion. Echocardiographic diagnosis was proved by the anatomopathologic examination. PMID- 2273724 TI - [Primary pulmonary hypertension]. PMID- 2273722 TI - [Risk factors of coronary artery disease in males during a 3 year follow up based on a cohort study in a selected region of Lublin]. AB - To assess changes in risk factors of coronary artery disease, examinations which had been performed in 1981 and 1982 were repeated in males aged 40-59, inhabitants of the district "Czechow" in Lublin. The study was based on Polish Experiment of Coronary Disease Multifactor Prevention assumptions 112 of 203 males investigated in 1981, 1982 underwent repeated examination (attendance rate 55%). Statistical analysis was performed only in twice examined subjects. Significant increase of blood pressure, body weight, total serum cholesterol and uric acid concentration was stated in comparison with their respective initial values. Significant decrease of HDL-cholesterol and no changes in serum triglycerides concentration were observed. The only positive stated alteration was a lower percentage of tobacco smokers. Diagnosis of coronary artery disease remained unchanged despite of increased risk factors levels (increase of mean Rose's index score from 5 in initial examination to 6.5 in a control one). This high increase in risk factors occurrence allows an unfavourable prognosis for future incidence of coronary artery disease and also demands to undertake vigorous prevention. PMID- 2273725 TI - [Pericardial effusion--management and diagnosis. I. Echocardiographic diagnosis]. PMID- 2273726 TI - [Pericardial effusion--diagnosis and management. II. Pericardiocentesis]. PMID- 2273727 TI - [Some aspects of arterial hypertension control in the prevention of ischemic heart disease]. PMID- 2273728 TI - [Rates of necrotic focus formation as a factor of prognosis of changes in indicators of central hemodynamics and microcirculation]. AB - The study was undertaken to examine 89 patients with acute myocardial infarction whose pulmonary pressures were measured under monitoring. The findings were compared with the time course of necrotic focal formation. The rate of the latter was found to determine central hemodynamic changes. High necrotization rates were ascertained to be directly related to the rate of pressure elevation in the pulmonary artery and the changes in stroke volume. PMID- 2273729 TI - [Diagnostic possibilities of precordial electrocardiographic mapping in the assessment of the results of dipyridamole test in patients with ischemic heart disease]. AB - The dynamics of cross-sectional, isochronic, and integral maps of electric potential distribution during the dipyridamole test was examined in 35 patients with verified coronary heart disease and 12 control patients. Basic differences were found in changes of excitation propagation velocities and positive potential amplitude in the groups examined. A local increase in R wave areas on the maps of positive potential differences was found to be the most significant mapping sign of transient myocardial ischemia (the sensitivity, specificity, and diagnostic accuracy being more than 97%). The diagnostic accuracy of an absolute or relative increase in the integral time and amplitude parameters of the mapping was 77% and 70%, respectively. PMID- 2273730 TI - [Role of inflammation markers in the evaluation of the clinical course of myocardial infarct]. AB - The authors examined the time course of changes in the levels of chlorine soluble mucoprotein and glycosaminoglycans as markers of an acute period of myocardial infarction. A significant correlation was established between the mass of the infarcted myocardium and the severity of its acute reaction as evaluated from the integral volume of various inflammation markers. A mathematical model of this relationship was proposed for patients with complicated and uncomplicated myocardial infarction. It was shown that it was possible to apply these parameters to the assessment of the severity and features of a myocardial infarction course. PMID- 2273731 TI - [Adaptive reserves of the myocardium in patients with ischemic heart disease]. AB - Myocardial adaptive reserves and their relation to the function of the adrenocorticohypophyseal system were examined in 69 patients with coronary heart disease. To define the adaptation of the myocardium during exercise, the index of myocardial adaptation was used. The function of the adrenocorticohypophyseal system was judged from blood levels of somatotropic hormone and cortisol before, at the peak, and 2 hours after exercise testing. A substantial decrease in myocardial adaptive capacity was found in CHD patients as compared with healthy subjects. These abnormalities proved to be more marked in patients with clinical signs of severe coronary failure than in those with moderate coronary circulatory failure. It was concluded that the function of the adrenocorticohypophyseal system was one of the factors determining myocardial adaptation during exercise in patients with coronary heart disease. PMID- 2273733 TI - [Changes in systemic and intracardiac hemodynamics during bicycle ergometry in patients with fibrillation arrhythmia treated with allapinin before and after sinus rhythm recovery]. AB - In atrial fibrillation, allapinine was shown to enhance rhythm by 7% and to increase cardiac output (p less than 0.05), as well as to slightly lower mean blood pressure and peripheral vascular resistance at rest. With exercise, both in atrial fibrillation, and sinus rhythm, there was a decrease in end-diastolic and end-systolic volumes of the left ventricle (p less than 0.05), a slight drop in ventricular ejection, that was statistically significant only with sinus rhythm (p less than 0.05). Physical exercise was not followed by an apparent additional aggravation of myocardial contractility, which makes allapinine preferable for long-term application to preserve sinus rhythm in patients without evident signs of heart failure. PMID- 2273732 TI - [Effectiveness of synthetic opioid peptide dalargin in acute myocardial infarction]. AB - The synthetic opioid peptide dalargin was examined for its potency in 86 patients with primary transmural myocardial infarction. The agent was shown to contribute to a decrease in initially elevated plasma cortisol levels and an increase in beta-endorphine and leucine-enkephaline concentrations. Myocardial contractility became normal by reducing the hyperfunction of its intact segments. This was evidenced by antistressor effects of the drug. However, no substantial effect was found on the clinical course of the disease, evolution of myocardial infarction, plasma CPK MB. The left ventricular contractility showed severe depression. PMID- 2273734 TI - [Effects of cordarone on the contractile function of the left ventricle]. AB - Acute intravenous administration of cordarone in a dose of 5 mg/kg was demonstrated to decrease the mean values of the peak increase rate in left ventricular pressure, circulatory myocardial fiber shortening velocity, ejection fraction, and specific peripheral vascular resistance by 19.5, 12.3, 10.3, and 26.2%, respectively. Less marked changes occurred in stroke and cardiac outputs. The effects were more pronounced during a more rapid intravenous administration of the agent, as well as in patients with lower myocardial contractility. Chronic administration of oral cordarone in doses of 200 to 300 mg a day had a low effect on cardiac hemodynamic parameters. Sinus bradycardia was significant in reducing the cardiac output (-10.8%). All the patients displayed prolonged Q-T interval that was maximally apparent in patients with the baseline prolonged interval (+13.1%). PMID- 2273736 TI - [Results of repeated coronary angiography in patients with unstable angina pectoris in a long-term follow-up]. AB - A total of 27 patients with unstable angina pectoris were examined in the acute period of the disease and 3.4 years later (from 30 to 51 months). A group of patients with a favorable outcome of unstable angina comprised 13 patients who had displayed no recurrences of disease exacerbation, but that of patients with an unfavorable outcome of unstable angina consisted of 14 patients who had had recurrences of symptoms of progressive angina until myocardial infarction (in 6 patients). Coronary angiography made during the first hospitalization showed that 40% of the patients exhibited a "complicated lesion" of the symptom-related artery, which further transformed to an uncomplicated one (Type I stenosis according to the classification by J. Ambrose et al.), the remaining developed coronary occlusion. Comparison of the specific features of a course of the disease and coronary angiographic findings revealed no relationship between the degree of symptom-related artery stenosis and the long-term outcome of unstable angina. PMID- 2273735 TI - [Newly manifested angina pectoris: role of lipids, lipoproteins and apoproteins A1 and B in the prognosis of ischemic heart disease]. AB - In 151 patients with first angina, a prognostic value of various factors: lipids, lipo- and apoproteins AI and B was studied in relation to the development of clinical remission 1-1.5 years after the onset of the disease. In multifactorial discriminant analysis, the predictors of clinical remission turned out to be heart rate reached at the maximal exercise during bicycle ergometry, the number of diseased segments with any visible degrees of stenosis, the course of the disease within the first month, the number of diseased segments with 70% or more stenoses, the number of afflicted vessels with 70% or more stenoses, the power achieved during bicycle ergometry, high levels of high density lipoproteins, and age. A prognostic value of the same factors in poor prognosis (myocardial infarction or death) was examined in 124 out of 151 patients. The predictors proved to be low total cholesterol levels, the power achieved during bicycle ergometry, smoking, a history of smoking, the number of diseased segments with any visible degrees of stenosis, the number of diseased segments with 70% or more stenoses, and the conditions promoting the development of the first anginal episode. PMID- 2273737 TI - [Differences in ways of development of myocardial infarct with severe and mild clinical course]. AB - In 43 dead and 83 survived patients with myocardial infarction, the severity of the disease was compared with hourly changes in indications of a precordial cardiogram made in the first 2 days. The signs were defined, which made it possible to predict a relapse of myocardial infarction 10-15 hours before its onset. The rate of transformation of myocardial lesion foci to necrosis was found to affect the lifespan of patients. The end mass of myocardial infarction was shown to be formed via confluence of individual necrotic foci which appear in the myocardium at various intervals. The early signs were described, which enabled severe cases of myocardial infarction, resulting in death to be differentiated from those leading to a patient's recovery. PMID- 2273738 TI - [Features of clinical manifestations of intermediate coronary syndrome in relation to the status of the coronary bed]. AB - Uni- and multifactorial analyses of clinical and angiographic findings were made in 32 patients with coronary heart disease concurrent with the intermediate coronary syndrome and 34 patients with progressive angina pectoris. A complex of clinical and angiographic signs was defined, which enabled these groups of patients to be differentiated. Exercise tolerance was the same in the two groups and related to the severity of coronary artery lesions. The efficacy of the antianginal therapy depended on the angiographic morphology of occlusive changes in the coronary bed and it was less in patients with Type II eccentric stenosis. PMID- 2273739 TI - [Changes in the level of polyunsaturated fatty acids, substrates and inhibitors of thromboxane and prostacyclin synthesis, in the blood of patients with cardiovascular diseases]. AB - The authors examined the ratios of blood free polyunsaturated fatty acids (PUFA), such as 20:3n6, 20:4n6, 20:5n3, and 22:6n3, which are substrates and inhibitors of synthesis of thromboxane A2 and prostacyclins that regulate both normal blood fluidity, and platelet adhesion and primary thrombogenesis. The object of the study was plasma from healthy subjects and 4 groups of patients with cardiovascular diseases: 1) large myocardial infarction; 2) resting and exercise induced angina pectoris; 3) large myocardial infarction; and 4) recurrent myocardial infarction. The levels of plasma free PUFA were measured by gas chromatography. Assessment of the PUFA ratios indicated that the risk for thrombogenesis increased in large and recurrent myocardial infarctions as compared to small myocardial infarction and angina pectoris both by reducing the relative levels of 20:3n6 and, in particular, 20:5n3, substrates of synthesis of only thrombolytics and vasodilators and by more greatly inhibiting the synthesis of prostacyclins than thromboxane with elevated 22:6n3 levels. PMID- 2273740 TI - [Possibilities of improving medical and socioeconomic effectiveness of the treatment of patients with myocardial infarct by physical training during posthospital stage of rehabilitation]. AB - Two groups of patients with myocardial infarction were compared for outcomes of rehabilitation. In group 1, rehabilitative therapy was performed by using conventional methods. In group 2, that was done on the basis of early activation and application of physical trainings 2 weeks following myocardial infarction. Physical trainings caused an increase in exercise tolerance and myocardial contractility and a decrease in left ventricular failure, which enhanced the proportion of individuals who returned to work and diminished deaths at a 2-year follow-up. PMID- 2273741 TI - [The nature of changes in lipid metabolism in patients with diabetes mellitus associated with ischemic heart disease]. AB - To elucidate the nature of lipid defects in patients with diabetes mellitus (DM) concurrent with acute myocardial infarction (MI), the study was undertaken to examine the serum concentrations of total cholesterol, triglycerides, alpha- and beta-lipoproteins with DM in the presence of acute MI. 40 non-diabetic patients with acute MI, 23 diabetics with postinfarct cardiosclerosis, and 17 non-insulin dependent diabetics without signs of coronary atherosclerosis. Urinary epinephrine and norepinephrine excretion was additionally determined in the acute period and 3-4 weeks after therapy. Homogeneous lipid metabolic parameters were found in CHD patients with and without DM and when transient hyperglycemia developed. The patients with acute MI exhibited some increase in lipid consumption to satisfy the energy need for the cardiovascular system, this being true for triglycerides in DM patients. The DM patients who showed low triglyceride levels had more frequently transmural MI and MI complicated with heart failure. Obesity and familial histories of DM and CHD in DM patients with acute MI were ascertained to be accompanied by reduced serum alpha-lipoprotein concentrations. PMID- 2273742 TI - [Pump function of the left ventricle during the stages of cor pulmonale development]. AB - Cluster analysis was used to examine the nature and magnitude of changes in left ventricular pump function in relation to the severity of primary bronchial obstruction in patients with non-atopic bronchial asthma (n = 45) and chronic obstructive bronchitis (n = 45). In the patients with obstructive lung disease, central hemodynamic changes were found to be determined by the bronchial patency and independent of the pathogenesis of the obstruction. During a remission there was a significant reduction in total peripheral resistance as compared to the values seen in healthy subjects, whereas in moderate or severe obstruction there was a marked increase in total peripheral resistance and a decrease in stroke volume and cardiac output. A drastic bronchial obstruction was followed not only by central hemodynamic changes, but a fall in ejection fraction and a rise in left ventricular end-systolic and end-diastolic volumes. PMID- 2273743 TI - [Comparative evaluation of a protective effect of adaptation to periodic hypoxia and stress in myocardial infarction]. PMID- 2273744 TI - [Effects of ethmozine on ventricular fibrillation threshold in acute occlusion of the coronary artery in dogs]. AB - In experiments on dogs with acute left descending coronary artery occlusion, ethmozine (3 mg/kg) was tested for effects on the threshold of ventricular fibrillation occurring as a result of high-frequency electric stimulation. Two hours after occlusion, the fibrillation threshold became significantly lower than the control values. Ethmozine used in this period enhanced the ventricular fibrillation threshold in some experiments and diminished it in the others. Four hours following the occlusion, the fibrillation threshold did not differ from the control ones. Ethmozine given in this period caused a significant increase in the ventricular fibrillation threshold. It was concluded that 4 hours after the onset of experimental myocardial infarction are the minimal time period following which administration of ethmozine failed to decrease electric stability of the heart. PMID- 2273745 TI - [Involvement of the autonomic nervous system in the cardiotonic effect of strophanthin]. PMID- 2273746 TI - [Possibilities of a numerical ECG study in the estimation of necrotic mass in myocardial infarct]. PMID- 2273747 TI - [Effects of antioxidant dibunol on central hemodynamics and several parameters of myocardial metabolism in patients with ischemic heart disease]. PMID- 2273748 TI - [Significance of the reversibility of focal ECG changes after endured myocardial infarction]. PMID- 2273749 TI - [Recovery of social activities by persons who had endured myocardial infarct based on the data of a 5-year follow-up]. PMID- 2273750 TI - [Study of Q-T interval changes due to the action of anti-arrhythmia drugs during isometric exercise]. PMID- 2273752 TI - [Addition to the calculation of blood stroke volume]. PMID- 2273751 TI - [Effects of mildronate on hemoglobin ligand spectrum in patients with ischemic heart disease complicated by coronary insufficiency]. PMID- 2273753 TI - [Initial clinical observations on the use of implantable automatic cardioversion defibrillators]. PMID- 2273754 TI - [Prostaglandins in the etiology and treatment of pulmonary hypertension]. PMID- 2273755 TI - [Vasopressin and arterial pressure]. PMID- 2273756 TI - [The Herbst-Volkheimer effect]. AB - More than 150 years ago the foundations were laid for the so-called HERBST effect which was subsequently forgotten. In the sixties the phenomenon was rediscovered by VOLKHEIMER at the Charite Hospital in Berlin and then reviewed through many experiments and publications. What is meant by the HERBST effect? If an experimental animal or even human being is given a larger amount of maize starch or also biscuits or some other products containing starch, starch bodies can be detected rapidly in venous blood already after minutes or half an hour later and in the urine after one hour and later. The term "persorption" has been coined for this interesting phenomenon. It is indeed surprising that it has met with so little attention. As a matter of fact, it constitutes the basis for our understanding of peroral immunization and of allergies. In the same way, feeding of carbon particles results in their appearance and detection in blood, kidney and urine. The same result is obtained by the intake of diatoms and what is even more important with meat fibres. I hope you are aware of the implications. When Professor NAGAI stayed in Berlin, we tried to receive the phenomenon. Since only a few cell nuclei are necessary for "genetic fingerprinting" we thought that after intake of 200 or 400 g of raw meat the type of food eaten could be determined from the urinary sediment by means of the fingerprint method which would be of forensic significance. Therefore, we eat meat and raw liver and examined the urinary sediment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2273757 TI - Differentiation of a human B cell hybridoma with interleukin-2 receptor. AB - A 6-thioguanine-neo-resistant clone, Raji 6-TGR-neoR was fused with pokeweed mitogen-stimulated B cells (PWM-B cells) obtained from a normal healthy donor, and selected by a new selection medium (HAT-neo). Two hybrid clones, HYNI-1 and HYNI-2, were established. These clones expressed surface IgG and HLA class II antigens derived from PWM-B cells, and they had about 20 more chromosomes than Raji 6-TGR-neoR. More significantly, one clone, HYNI-2, expressed interleukin-2 receptor on the cell surface, and generated IgG when stimulated with recombinant interleukin-2. These findings indicate that the HYNI-2 is a good model for studying human B cell differentiation. PMID- 2273758 TI - A long-term surveillance of occupational health hazards faced by cadmium workers. AB - The decrease or damage of renal tubular functions by cadmium (Cd) exposure is designated as the critical effect on human body. When the Cd workers suffer from tubular damage, it is matter of concern whether the damage is reversible or irreversible. In this study, chronic influences of long-term exposure to Cd dust or fumes in the working environment were clarified. Besides the survey on Cd contents in work environment and production amounts of Cd pigments in the factory, the changes of Cd concentration in blood and urine, beta 2-microglobulin (beta 2MG) in serum and urine, C beta 2-MG/Ccr, the rate of tubular reabsorption of phosphorus (% TRP) and other laboratory examinations in 7 Cd pigment workers were observed for the past 15 years. In almost workers, the changes of Cd concentrations in blood and urine, beta 2MG in urine, and C beta 2MG/Ccr basically paralleled those of Cd concentrations in working environment. In some workers the fluctuations of beta 2MG in urine, C beta 2MG/Ccr and %TRP did not paralleled those of environmental Cd concentration and they were very variable. From the results obtained, it is stressed that the long-term follow-up studies on environmental Cd concentrations and analysis of biological indicators are necessary to determine the degree of the renal tubular dysfunction by Cd. PMID- 2273759 TI - Uptake and distribution of chromium in isolated rat hepatocytes and its relation to cellular injury. AB - In order to study the difference of uptake and distribution between hexavalent (Cr6+) and trivalent (Cr3+) chromium in isolated rat hepatocytes, the cells were incubated with Cr6+ or Cr3+ (1 mM Cr) at 37 degrees C for up to 60 min. Leakage of lactate dehydrogenase from the hepatocytes into the suspension medium as an indicator of cellular injury was facilitated by Cr6+ (K2Cr2O7) at 60 min of incubation, whereas Cr3+ [Cr(NO3)3] had no effect. After 60 min of incubation with Cr6+, about 33% of the added Cr was found in the hepatocytes, whereas incubation with Cr3+ resulted in transfer of about 66% of the added Cr to the cells. After 20 and 40 min of incubation with Cr6+, about 39% of cellular Cr was found in the cytosolic fraction of hepatocytes, followed by a reduction to about 35% after 60 min of incubation. However, Cr detected in the cytosolic fraction of hepatocytes incubated with Cr3+ was about 1% of cellular Cr. Cr-binding substances in the cytosolic fraction of hepatocytes incubated with Cr6+ were eluted with two Cr peaks by Sephadex G-200 chromatography. These Cr-binding substances in the low-molecular-weight fractions were separable into at least two substances by thin-layer chromatography. These results suggest that Cr6+ readily passes through the cell membrane and combines with substances already present in the cytosolic fraction of hepatocytes, unlike metallothionein induced by cadmium, followed by detoxification. Consequently, cellular injury might be induced by Cr6+ which could not combine with LMCr in the cytosolic space of the hepatocytes. PMID- 2273760 TI - Staphylococcal food poisonings in Tokyo, with special reference to the coagulase types of the isolates. AB - Staphylococcus aureus strains isolated from the 391 confirmed cases of staphylococcal food poisonings in Tokyo, in the period 1967-1986, were studied for their coagulase types. Consequently, it was found that all the isolates could be classified into the coagulase types II, III, VI and VII. Namely, the isolates from 54 (13.8%) of 391 outbreaks were typed as type II, 72 (18.4%) as type III, 38 (9.7%) as type VI, and 227 (58.1%) as type VII, respectively. Throughout the investigation, it was found that the outbreaks of staphylococcal food poisonings due to coagulase type VII organisms were remarkably increased since 1975. PMID- 2273761 TI - [The haptoglobin-streptococcus relationship]. AB - In many experiments beginning in 1977 Prof. O. Prokop and Prof. W. Kohler discovered that the human haptoglobins are able to agglutinate group G streptococci, but the reaction depends on the haptoglobin type. Haptoglobins of the types Hp 2-2 and Hp 2-1 are complete agglutinins and haptoglobin of the Hp 1 1 type is incomplete ("blocking") antibody. Later it was found that streptococci with the T4--antigen (from Lancefield types A, C and G) are suitable for the test. PMID- 2273762 TI - [The surgical treatment of chronic hepatitis and liver cirrhosis at the compensation stage]. AB - The authors have analysed the results of operative treatment of 120 patients with chronic hepatitis and liver cirrhosis at the stage of compensation. Periarterial nervectomy of the common hepatic artery was performed in 30 patients, extraperitonealization of the right hepatic lobe with laser irradiation--in 42, periarterial nervectomy of the common hepatic artery with extraperitonealization of the right hepatic lobe and laser irradiation--in 48. The results of periarterial nervectomy of the common hepatic artery with extraperitonealization of the right hepatic lobe and use of laser irradiation were the best. PMID- 2273763 TI - [Possibilities for predicting infectious complications after surgery of patients with chronic calculous cholecystitis]. AB - Examined were 92 patients with chronic calculous cholecystitis, who were admitted to the hospital for the elective operative intervention. In these patients before the operation, T-lymphocytopenia, reduction of the helpers/suppressors index, number of the theophylline-resistant lymphocytes, IgA level in the blood serum, increase of the CIC number were noted. PMID- 2273764 TI - [Comprehensive therapy of obstructive jaundice with neoplastic origin]. AB - The authors treated 67 patients with jaundice on the ground of biliopancreatoduodenal tumors. Of them, 49 underwent the palliative operations. In 31 patient, the conventional two-stage treatment was employed. The postoperative complications occurred in 28.6% of the patients. The lethality was 20.8%. Examination for 1-3 days, intensive preoperative preparation, antibacterial prophylaxis, regional chemotherapy were performed in 18 patients. The incidence of postoperative complications in these patients was 11.2%, the lethality--5.6%. PMID- 2273766 TI - [Diagnostic complexities of primary liver cancer in selecting patients for transplantation]. AB - In examination of 23 patients with primary cancer of the liver, who were considered as the candidates for orthotopic liver transplantation, the authors established the necessity for performance of the complete clinico-laboratory instrumental investigation with mandatory use of the ultrasound study, scintigraphy, computed tomography with target puncture biopsy of a hepatic neoplasm. PMID- 2273765 TI - [Ultrasonic diagnosis of focal lesions of the liver before reoperation]. PMID- 2273767 TI - [An experimental validation of organ-preserving operations in traumatic lesions of the parenchymatous organs]. AB - Resulting from the experiment performed on 32 dogs, the authors have established that the use of technology of tissue bioinhibition and cryogenic influence led to local cryopreservation, hypercoagulation and change in the physical properties of the damaged parenchyma. This contributes to successful performance of the organ preserving operations and prevents the development of early and long-term postoperative complications. PMID- 2273768 TI - [Clinical results of transduodenal sphincteroplasty and choledochoduodenostomy in acute cholecystitis]. AB - In acute cholecystitis of the 460 patients, in 126, besides the cholecystectomy, the transduodenal sphincteroplasty (79) and supraduodenal choledochoduodenostomy (47) were performed. The postoperative lethality was 6.3 and 4.2%, respectively, mean duration of treatment of the patients at the hospital after the operation - 18.5 and 23.5 days. The excellent and good long-term results were noted in 78 and 73% of the patients examined. A conclusion is drawn, that sphincteroplasty and choledochoduodenostomy in complicated acute cholecystitis is more preferable, than choledochotomy and external drainage of the common bile duct. PMID- 2273769 TI - [The treatment of acute cholecystitis]. AB - The authors treated 462 patients with acute cholecystitis. Operated on were 220 patients. Of them, 53.6%--at the first 24 hours after admission. In 26.3% of the patients, peritonitis was an indication for the operation. The postoperative lethality was 4.1%. PMID- 2273770 TI - [Terminolateral choledochoduodenal anastomosis]. AB - A technique of the terminolateral choledochoduodenal anastomosis formation in 37 patients with impaired patency of bile ducts and indurative pancreatitis in presence of the common ampulla of the bile duct and pancreatic duct is presented. After the operation, the complications developed in 5 patients, 2 died. The result of treatment in observation of up to 4 years in 28 patients is good, in 2- satisfactory, in 2--bad (reoperated). PMID- 2273771 TI - [The use of laser scalpel in the surgical treatment of cholecystitis]. AB - A comparison of the results of 169 cholecystectomies with the use of a laser scalpel and 160--conventional methods was carried out. The CO2-laser was used for exposure of the gallbladder and coagulation of tissue of the liver in the region of its bed. Hemo- and cholestasis in all the cases was reliable, and due to this fact in 27% of the patients, the subhepatic recess was not drained. The incidence of complications after the elective cholecystectomy reduced by 11%, after the emergency one--by 9%, the lethality reduced considerably. PMID- 2273772 TI - [Suppurative pylephlebitis in suppurative cholecystitis and cholangitis]. PMID- 2273773 TI - [Disorders of immunoreactivity in acute cholecystitis in middle-aged and elderly patients and their correction in preventing postoperative complications]. AB - In elderly and senile patients with acute cholecystitis, the decrease in the content of T-lymphocytes and their functional activity, number of B-lymphocytes and IgG level, increase in the IgM and IgA content were noted. The attenuation of non-specific protective mechanisms was revealed. In patients, who underwent the purposeful immunocorrection with prodigiosan, proper-myl, methyluracil and staphylococcal adsorbed anatoxin, the number and activity of T-lymphocytes normalized, number of B-lymphocytes increased at the time of operation and after it. This contributed to reduction of the incidence of the inflammatory complications 3-fold. PMID- 2273774 TI - [Immunoreactivity of patients with pathology of the liver, gallbladder and biliary tract]. AB - In a work, the comparative analysis of the state of immunological reactivity in 25 patients with pathology of the liver, gallbladder and bile ducts and in 25 healthy subjects is presented. In patients, T-lymphocytopenia, impaired ratio of subpopulations of the helpers and suppressors, increase in the absorptive and metabolic activity of neutrophilic granulocytes, lysozyme activity of the blood serum, decrease in the immunoglobulin G content are observed. PMID- 2273775 TI - [Combined use of peritoneo-atrial shunting and endoscopic sclerotherapy of esophageal varicose veins in treating liver cirrhosis with portal hypertension and resistant ascites]. AB - The authors in 39 patients with liver cirrhosis and intractable ascites performed peritoneoatrial shunting (PAS), in 16--PAS in combination with prophylactic endoscopic sclerotherapy (ES) of gastric varices (GV). Prophylactic use of ES before PAS permitted to reduce more than 3-fold the incidence of postoperative bleeding from EV. PMID- 2273776 TI - [Duodenitis in surgical diseases of the organs of the hepatopancreaticoduodenal region]. AB - In examination of 74 patients with surgical diseases of the hepatopancreatoduodenal organs, the authors have established the deepest morphological changes in the duodenal mucosa in patients with complicated form of cholelithiasis and chronic impairment of duodenal patency. Impaired motility of the duodenum contributed to reproduction of microflora in its contents, and led to the development of duodenitis in these patients. PMID- 2273777 TI - [Duodenal motility disorders in calculous cholecystitis]. AB - In acute calculous cholecystitis, the impairment of motor duodenal function was revealed in 81.6% of the patients, in chronic calculous cholecystitis-in 72.2%. Hypotension in the duodenum is fraught with the development of duodenostasis after cholecystectomy. The reliability of intraoperative duodenal manometry in studying the motor duodenal activity in patients with calculous cholecystitis is substantiated. PMID- 2273778 TI - [Comparative characteristics of nonparasitic and opisthorchiasis cysts of the liver]. AB - The authors observed 24 patients with opisthorchiasis and 14--with nonparasitic cysts of the liver. No essential differences in the tactics of surgical treatment of these cysts were noted. In medium-size and large cysts, the operative treatment--excision of cystic walls with omentoplasty, liver resection--is recommended; in small opisthorchiasis and nonparasitic cysts--dynamic observation with the performance of ultrasound scanning. PMID- 2273779 TI - [Cholecysto-intestinal anastomoses in the treatment of obstructive jaundice with neoplastic origin]. PMID- 2273780 TI - [The treatment of primary sclerosing cholangitis]. PMID- 2273781 TI - [Cholelithiasis in patients with primary extrahepatic portal hypertension]. AB - The results of treatment of 17 patients who had primary extrahepatic portal hypertension in combination with cholelithiasis are analysed. Of them 13, were operated on. In presence of the extended strictures of the bile ducts, the performance of hepaticojejunostomy is mandatory. In dominating involvement of the extrahepatic bile ducts, the endoscopic papillotomy as a definitive intervention is expedient. In asymptomatic course of cholelithiasis, the operation is not expedient. PMID- 2273782 TI - [Characteristics of hemostasis in liver surgery]. PMID- 2273783 TI - [Ischemic infarct of the liver]. PMID- 2273784 TI - [The immune system of the body and peptic ulcer of the stomach]. PMID- 2273785 TI - [A cholecysto-diaphragmatico-pleurobronchial fistula]. PMID- 2273786 TI - [Aplasia of the gallbladder]. PMID- 2273787 TI - [Anomalies of the biliary tract as latent risk factors in biliary surgery]. PMID- 2273788 TI - [Choledocholithiasis simulating a tumor of the distal common bile duct]. PMID- 2273789 TI - [Iatrogenic damage to the retroduodenal portion of the common bile duct]. PMID- 2273790 TI - [Pylephlebolithiasis simulating choledocholithiasis]. PMID- 2273791 TI - [Combination of acute phlegmonous cholecystitis and a giant hemangioma of the liver]. PMID- 2273792 TI - [Isolated subcutaneous injuries to the gallbladder]. PMID- 2273793 TI - [Isolated extraperitoneal rupture of the gallbladder]. PMID- 2273794 TI - [Subcutaneous rupture of the gallbladder]. PMID- 2273795 TI - [Actinomycosis of the gallbladder]. PMID- 2273796 TI - [A case of multiple biliary-colonic fistulas]. PMID- 2273797 TI - [An anomaly of the biliary tract]. PMID- 2273798 TI - [Anomaly of the bile ducts in a patient with situs inversus]. PMID- 2273799 TI - [The validation of early surgical intervention in acute cholecystitis in middle aged and elderly patients]. PMID- 2273800 TI - [A rare case of a common bile duct cyst]. PMID- 2273801 TI - [Endoscopic papillosphincterotomy in confluence of the pancreatic and common bile ducts]. PMID- 2273802 TI - [Intraoperative injury to the extrahepatic bile ducts during cholecystectomy causing isolated cirrhosis of the right lobe of the liver]. PMID- 2273803 TI - [Campylobacteriosis as a cause of biliary tract diseases]. PMID- 2273804 TI - [The choice of treatment method in amebic liver abscess]. PMID- 2273805 TI - [Rupture of a nonparasitic cyst of the left lobe of the liver into the abdominal cavity]. PMID- 2273806 TI - [Right-sided hemihepatectomy in echinococcosis in a 72-year-old female patient]. PMID- 2273807 TI - [The acetylating capacity of the body studied for the purpose of individualizing patient chemotherapy]. PMID- 2273808 TI - [Liver damage in nonpenetrating gunshot wounds of the abdomen]. PMID- 2273809 TI - [Calcified cyst of the spleen]. PMID- 2273810 TI - [A method of cholecystostomy]. PMID- 2273811 TI - [A device for drainage of the common bile duct via the stump of the cystic duct]. PMID- 2273812 TI - [A device for papillosphincterotomy]. PMID- 2273813 TI - [A method for returning the bile into the duodenum of patients with an external biliary fistula]. PMID- 2273814 TI - [Procedural aspects of the diagnosis and surgical treatment of acute cholecystitis in patients with risk factors]. AB - In the treatment of acute cholecystitis in 1786 patients, in 1127 the risk factors being registered, the active surgical tactics was employed (performance of the operative intervention 3-6 h after admission in absence of the effect of conservative treatment), the endoscopic, ultrasound and CT methods of investigation, in indications, percutaneous transhepatic microcholecysto- or microcholangiostomy were widely used. The use of the measures mentioned contributed to reduction of the number of complications and postoperative lethality in patients with complicated forms of acute cholecystitis and concomitant diseases. PMID- 2273815 TI - [Surgical tactics in fresh injuries of ligaments of the knee joint]. AB - Experience with the clinic in operative treatment of fresh damage of the ligaments of the knee joint (90 cases) is analysed. The authors dwell on the problems of diagnosis and the choice of the surgical tactics in isolated and multiple injuries to the ligaments. It is shown that operative restoration of the damaged ligaments in the earliest period after the trauma makes it possible to normalize the relationship of the injured elements. Good results were produced- complete stability and restoration of the function of the joint allows the suggested tactics to be recommended for wide introduction into traumatological practice. PMID- 2273816 TI - [Results of the treatment of patients with torsion of the sigmoid]. AB - The results of treatment of 204 patients with torsion of the sigmoid colon are analysed. Total postoperative mortality was 14.2%. Sixty-eight patients were subjected to palliative operations of the type of ++de-torsion or ++de-torsion in combination with mesosigmoplication and sigmopexy. In this group of patients, 20.5% underwent a second operation for a recurrence of the disease in different periods after the first operation. The mortality rate after palliative operations was 13.2%. Resection of the sigmoid colon with an end-to-end anastomosis was carried out in 87 patients. The postoperative mortality was 13.7%. There were no fatal outcomes among patients who were treated by radical operation carried out in a planned order of preliminary detorsion. In 11.7% of cases, sigmoid torsion was complicated by gangrene. Seven patients (29.1%) died in the postoperative period. PMID- 2273817 TI - [Atropine resistance and its significance in the selection of the method of surgical treatment of duodenal ulcer]. AB - Medical vagotomy with atropine allows two types of patients with duodenal ulcer to be distinguished--atropine-resistant and atropine-sensitive. A complicated course of the disease, high values of nocturnal gastric secretion before the operation, and positive Hollander's insulin test after vagotomy are encountered most frequently in atropine-resistant patients. The values of gastrin are significantly higher in these patients than in atropine sensitive patients. In 3 year follow-up periods, recurrence of the ulcer after vagotomy was revealed in 6.5% of atropine-resistant patients but in none of the atropine sensitive patients. Medical vagotomy with consideration for atropine sensitivity may be a reliable prognostic criterion in the choice of the operative intervention in patients with duodenal ulcer. PMID- 2273818 TI - [Peritoneovenous shunt in resistant ascites in patients with portal hypertension]. AB - Experience in 100 operations for the creation of a peritoneovenous shunt in 63 patients with portal hypertension and resistant ascites showed that in careful selection of patients and determination of contraindications this operation is an effective method for the treatment of resistant ascites in patients with portal hypertension. The shunt increases diuresis, reduces the volume of the abdomen, makes laparocentesis unnecessary, improves the patients' general condition and allows some of them to be prepared for interventions on the organs of the portal system which are more radical in character. PMID- 2273819 TI - [Concerning the letter to the Editor by Ia.D. Vitebskii ("Khirurgiia", 1990, No. 3)]. PMID- 2273820 TI - [Treatment of open fractures during patients' evacuation]. PMID- 2273821 TI - [Postoperative complications and mortality in primary-reconstructive combined resection of the intestines]. PMID- 2273822 TI - [Hazards in surgery of the duodeno-jejunal passage]. PMID- 2273823 TI - [Treatment of suppurative-necrotic processes in the controlled germ-free environment with drug aerosols]. PMID- 2273824 TI - [Plastic surgery of post-burn cicatricial deformities and contractures of the neck with expanded scapular flaps and microvascular anastomoses]. PMID- 2273825 TI - [A surgical method of the treatment of onychogryphosis of the hallux]. PMID- 2273826 TI - [A method of dermatoplasty of the thumb]. PMID- 2273827 TI - [Combined dermatoplasty of the heel after 4th-degree frostbite]. PMID- 2273828 TI - [Tarsal tunnel syndrome in sportsmen]. PMID- 2273829 TI - [Gas-induced rupture of the stomach].